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pmc-6571248-1 | A 49-year-old woman had a snakebite on her left foot while walking on the street. The killed snake was identified as T. stejnegeri. The patient developed severe pain and swelling in the left foot, local erythema, and ecchymosis a few minutes after the bite. She was taken to a nearby clinic where she was given base treatment, including cleaning the wound and hemostasis. For further treatment, she was subsequently transferred to the hospital. On examination, the vital signs were found to be stable and the left foot was markedly swollen. The neurological examination was essentially normal on admission. She was immediately treated with three 10-mL intravenous injections of polyvalent anti-snake venom serum. Meanwhile, she was also injected with adsorbed tetanus toxoid. She also received ceftriaxone and other supportive therapy. The laboratory findings were as follows: mild leukocytosis and negative coagulation function and fibrin degradation products. The patient developed right-side weakness and speech disturbances on the fourth day after the bite. She also had nonfluent aphasia with difficulty in expression and understanding and right spastic hemiparesis involving the face, arm, and, to a lesser degree, the leg. The examination revealed that edema in the left lower extremity was obvious. The nervous system examination showed that the consciousness was clear. The patient had mixed aphasia. The bilaterally round pupils, about 3 mm in diameter, were sensitive to light reflection. Further, the nasolabial fold was shallow on the right, the tongue deviated to the right, and the right limb muscle strength was 0. The left limb muscle strength was of grade 5, the Babinski sign on the right side was positive, and the National Institutes of Health Stroke Scale (NIHSS) score was 18 points. The brain computed tomography scan showed no cerebral hemorrhage symptoms. Magnetic resonance imaging showed acute ischemic infarct in the left territory (Fig. ). Magnetic resonance angiography of the cerebral circulation revealed no abnormalities. Electrocardiogram demonstrated sinus tachycardia. The color Doppler study showed no arterial or venous thrombosis in the lower limbs. The workup for the other stroke risk profiles, including lipoprotein (a), serum homocysteine, and antithrombin III; carotid Doppler; and 2-dimensional echocardiography was normal.
The patient was treated with neuroprotective therapy (edaravone 30 mg, once a day) for 10 days and antiplatelet aggregation (clopidogrel 75 mg, once a day). Also, polyvalent anti-snake venom serum was injected. Two weeks later, the swelling in the left lower extremity of the patient disappeared, and the right limb muscle strength recovered to grade 3. The patient had mixed aphasia, and the NIHSS score was 13 points. The myocardial injury markers and coagulation indexes were all within the reference range. The patient was discharged. After discharge, the patient continued to take clopidogrel for 3 months. The follow-up showed that the modified Rankin scale score was 4 points after 3 months.
Ethical approval was not necessary because our study was a case report.
The patient signed informed consent for publication of the case. |
pmc-6571256-1 | A 45-year-old Chinese male, without any positive medical and family history, was admitted for intermittent mild hemoptysis (<30 mL/24 hour) for previous 2 weeks, with no other complaints. Physical examination was unremarkable. Laboratory test revealed negative T-SPOT.TB test and the normal inflammatory makers including white blood cells, high-sensitivity C-reactive protein, and procalcitonin. Enlarged mediastinal silhouette was found on the chest roentgenogram. Transthoracic echocardiography (TTE) suggested the possibility of PAPVC involving left upper pulmonary vein. No ASD, patent foramen ovale or other cardiac anomalies were detected. In addition, TTE revealed mild tricuspid regurgitation with pulmonary artery systolic pressure estimated of 35mmHg. Further assessment by contrast-enhanced computed tomography (CT) showed the anomalous left upper pulmonary vein draining into the left brachiocephalic vein (Fig. A and B). No occupying lesion, pneumonia, tuberculosis, bronchiectasis, and arteriovenous malformation were found on the contrast-enhanced CT. In addition, hematocele was detected on the opening of the left upper lung bronchus while no bronchial tumor was detected by bronchoscopy. According to extensive workup, the common causes of hemoptysis, including malignant tumor, tuberculosis, pneumonia, fungal infections, bronchiectasis, and bronchitis, were excluded. A multi-disciplinary meeting was held and concluded that patient may not benefit from a PAPVC repair because hemoptysis remission could not be guaranteed. After full communication with patient, the decision of left upper lobectomy was finally made as definitive treatment for both hemoptysis and PAPVC.
Video-assisted thoracoscopic the left upper lobectomy was performed under one-lung ventilation. The anomalous vein originated from the root of left upper pulmonary vein, traversed aortic arch and connected to the left brachiocephalic vein (Fig. C and D). Left upper lobectomy with ligation of the anomalous vein was performed successfully. The patient had an uneventful recovery without any complications and was discharged home on the 5th postoperative day. The patient has been followed up for almost 2 years without recurrence of hemoptysis. |
pmc-6571332-1 | A 51-year-old woman underwent hysterectomy and pelvic lymph node dissection for uterine cancer when she was 48 years old, and lymphedema developed in the left leg soon after the operation. She had one episode of cellulitis. Despite wearing elastic stockings, lymphedema worsened, and she visited our institution at the age of 49 years. She was diagnosed with lymphedema based on lymphoscintigraphic finding. There was a development of collateral lymphatic vessels and dermal backflow in bilateral lower leg (See figure, Supplemental Digital Content 1, which displays lymphoscintigraphic findings. Collateral lymphatic vessels were observed in the bilateral lower legs. Lymphatic function in the left thigh was impaired, ). She had no allergies or other pertinent medical histories.
LVA was performed at the age of 50 years. The postoperative course was uneventful, and lymphedema improved. However, lymphedema worsened again at 1 year postoperatively after taking a long flight, although she wears elastic stockings daily. A second LVA was planned (Fig. ).
Preoperative indocyanine green (ICG) lymphography showed a linear pattern in the right leg. Dermal backflow was observed in the left thigh and lower leg. There was no linear pattern in the area (left lower leg) where the lymphatic thrombus was found afterward. Preoperative echography showed 2 hypoechoic circles measuring about 0.5 mm in diameter that did not collapse with pressure from the probe, although the veins collapsed with pressure (Fig. ). Compared with lymphatic vessels, veins usually collapse more easily under pressure, because the inner pressure of the lymphatic vessels is higher than that of the veins. In this case, the 2 circles did not collapse under pressure, and we surmised that the inner pressure prevented collapse. The hypoechoic circles extended proximal and distally and did not have flow with on color Doppler mode.
During LVA, we identified 2 parallel white vessels beneath the superficial fascia. Two vessels were in close contact. We diagnosed these as lymphatic vessels because of the location and appearance and the fact that they ran in parallel, which is not usually observed with other vessels or nerves. When we incised the vessels, white material was extruded (Fig. ). A diagnosis of lymphatic thrombosis was made, and we concluded that the vessels did not collapse with pressure from the probe during echography because of thrombus. Intraoperative echography revealed the same findings, that is, a hypoplastic circle without collapse by probe pressure, 15 cm distal from the incision, which indicated that there was lymphatic thrombus in at least 15 cm. We ligated the lymphatic vessels, closed the wound at this site, and performed LVA at other sites (4 sites in the left and 1 site in the right leg). Though the postoperative course was uneventful, the patient’s lymphedema did not improve postoperatively. This may be partially because the patient gained weight after LVA, and there is another possibility that postoperative thrombus formed within the anastomosis site had harmful effect for lymphedema, although it is difficult to confirm.
Histopathological examination showed a thickened smooth muscle layer (tunica media) in the lymphatic vessels (See figure, Supplemental Digital Content 2, which displays histopathological findings of the lymphatic vessel and the lymphatic thrombus. (a) The lymphatic vessel (a) and the lymphatic thrombus (b) (×20, H&E). Thickened smooth muscle layer (tunica media) in the lymphatic vessels is observed. (c) The lymphatic vessel (×100, D2-40). The endothelial cells of the vessel were negative for D2-40, ). Fibrous thickening of the tunica intima was observed, and the inner lumen was narrow. The inner layer of the vessel was negative for D2-40, which is a marker to stain the lymphatic endothelial cells. In the thrombus, hyperplasty of fibroblasts and organization were found (Fig. ). We did not observe hyperplasty of the lymphatic endothelial cells, which are positive for D2-40 within the thrombus. |
pmc-6571405-1 | A 42-year-old male patient suffered a high falling injury (Table ), causing pain, swelling, deformity, and limited mobility on his right hip. Physical examination revealed that the right hip was slightly swollen, there existed slight tapping pain around the greater trochanter, the midpoint tenderness of the inguinal ligament was positive, and the flexion of the hip was obviously limited. No significant bone rub was touched. Bilateral lower limbs had normal sensation, the temperature of lower extremity skin was normal, the pulsation of dorsal pedal artery can be touched, and the muscular tension of both lower extremities was normal.
The hip x-ray exhibited the discontinuity of bone in the right femoral neck (Fig. ). Three-dimensional (3D) CT images showed that the right femoral neck bone was discontinuous and linear translucent (Fig. ). The patient was primarily diagnosed as FNF. In accordance with Garden typing,[ it was classified as Garden I.
The whole hip was scanned by CT preoperatively, and the result was shown in Fig. . The image information was recorded in the compact disc read-only memory, which could be read by a computer navigation workstation. The length, diameter, and the optimal trajectory of the PCS were designed at the navigation workstation preoperatively (Fig. ).
The operation was performed under general anesthesia (intubation: propofol, 200 μg/kg, Qingyuan Jiabo Pharmaceutical Co., Ltd. China; fentanyl, 250 μg, RenFu LLC, YiChang, China; midazolam, 2 mg; maintenance: propofol, 0.2–0.5 mg/kg/h, Enhua Pharmaceutical Limited by Share Ltd., JiangSu, China). Short-acting muscle relaxants were provided only during the intubation. When the anesthesia worked, the patient was placed in the supine position.
First, a patient tracker (Stryker Leibinger GmbH & Co., Freiburg, Germany), operated with the Navigation System II-CART II with SpineMap 3D 2.0 software (Stryker Navigation, Kalamazoo, MI), was outfitted on the iliac crest at the beginning of the operation. The system's C-arm tracker, patient tracker, and guide needle sleeve tracker were all activated. After 190° scanning was performed at the center of the femoral neck, 3D images of the lesion were captured. Subsequently, preoperative and intraoperative CT images were matched to provide clear guidance for the guide needle sleeve.
Second, the screw view mode was selected in the navigation workstation. Besides, the position of the guide needle sleeve device was adjusted until the direction of guide needle sleeve completely complied with the planning PCS trajectory, and the guide wire was placed once the right lower corner image showed green (Fig. ). At the end of the operation, cannulate screws were inserted sequentially through the implanted guide wire.
Finally, x-ray and CT scan were performed to verify whether the screw was in good position (Figs. and ). Postoperatively, the right lower extremity was abducted 15° to 30° under the fixed anti-rotation shoes. Four weeks after surgery, patients could get out of bed with double crutches. Four to 6 months after the operation, the patient could walk without crutches after fracture healing.
Position of cannulate screw in femoral neck: grade 0 was defined as excellent (the distance from the outer edge of the screw to the cortex of the femoral neck was 2–5 mm), grade 1 as good (>5 mm), grade 2 as general (<2 mm), and grade 3 as bad (penetration the cortex of femoral neck)[ (Table ). The deviation of each screw's femoral neck-shaft angle and anteversion angle: the angles between the longitudinal axis of the 3 cannulate screws and the axis of the femoral neck were measured from the anteroposterior and lateral radiographs, respectively (Fig. , Table ). Neck coverage area of the femoral neck was calculated[: neck coverage area = D2/D1. D1: the diameter of the femoral neck at the fracture level. D2: the distance from the inferior border of the most distal screw to the superior border of the proximal screw (Fig. , Table ). Furthermore, the time for designing the screws, implanting the guide wire and inserting the screws, the amount of bleeding, the guide wire drilling attempts, fluoroscopic time and Harris hip scores were assessed (Table ). |
pmc-6571421-1 | A 41-year-old man presented to our Neurology Department with pain at the level of the right shoulder and right interscapular–vertebral region, with onset for about 6 months. In the last 30 days, the pain exacerbated and radiated in the anteromedial part of the arm and clavicular area. The patient also reported pain in the joints of the distal part of upper and lower limbs, especially in the small joints, which afterward became swollen.
The patient presented with a medical history of arterial hypertension for the last 10 years, treated with beta-blockers and sartans, and he was a heavy smoker (in the last period he used only electronic cigarettes).
The neurologic examination was normal, except for slightly diminished deep tendon reflexes of the lower limbs. The patient reported pain that did not correspond to any radicular or nerve territory, which was exacerbated by pressure on the distal third of radius and ulna, but was not related to active or passive movements of the cervical spine. The general examination showed clubbing of the fingers and toes (not mentioned initially by the patient, but present for about 1 year) with an increase of the shoe size of more than 1.5 sizes, enlargement of the large joints, swollen extremities with a tubular appearance (Figs. and ), a right lateral cervical mobile, painless adenopathy of 1 cm diameter, and pachydermia with thickening of the skin of the scalp, forehead, and fingers, with cranial skin folds.
Cervical magnetic resonance imaging performed in another clinic before the admission to our department showed the presence of disc protrusions from C2 to C7, with concomitant C2, C4, and C5 root compressions. The electrophysiological study revealed an active denervation in the territory of the right C5, C6, and C7 roots.
The radiographic examinations of the upper and lower limbs depicted symmetric osseous abnormalities, typical for periostosis, and linear halving of the diaphysis with an increase in the bone circumference. There were no fractures or cortical destruction (Figs. and ). Transthoracic echocardiography and electrocardiography were normal.
The computed tomography (CT) of the thorax, abdomen, and pelvis revealed the presence of a 23/19 mm (transverse) and 20 mm (cranial–caudal) mass lesion, respectively, having speculated margins, contrast enhancement, and areas of necrosis at the level of the dorsal segment of the right upper pulmonary lobe. The mass presented several extensions to the pleura and determined pleural invasion (Figs. and ). In addition, multiple mediastinal adenopathy were noticed, and some of them presented central necrosis. No oncologic abnormalities were found at the examination of the abdomen and pelvis. Also, the cerebral CT scan did not show any pathological findings.
Laboratory findings were normal, except for the presence of inflammatory syndrome, slight anemia, and high values of vascular endothelial growth factor (VEGF) (1291 pg/mL, with normal values less than 100 pg/mL).
The patient was admitted to the Pneumology Clinic, where biopsy from the lateral cervical adenopathy was performed (tumor excision was not an option, due to the presence of multiple adenopathy). The anatomopathological examination of multiple fragments from the lymph node revealed multiple neoplastic infiltrates, suggestive of adenocarcinoma metastasis.
Positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose confirmed the presence of the pulmonary malignant tumor with multiple active adenopathy.
Based on the clinical examination that revealed signs and symptoms suggestive of Pierre Marie–Bamberger syndrome, the X-ray examination that showed abnormalities compatible with the same pathology mentioned earlier, and on the positron emission tomography and histologic findings, the diagnosis of pulmonary adenocarcinoma with lymph nodes metastases and paraneoplastic hypertrophic osteoarthropathy was established.
The patient received treatment with nonsteroidal antiinflammatory drugs and opiate analgesics, which relieved the pain without any adverse event; he was then referred to the Oncology Department for further treatment of the primary pathology. The patient was treated with different types of chemotherapeutics, immunotherapy, and gamma-knife radiotherapy for cerebral metastases. Unfortunately, the disease progressed despite all of these therapeutic measures and the patient died 9 months later. |
pmc-6571432-1 | A woman in her 40s noticed a left axillary mass in November 2013, and in January 2014 she underwent left axillary tumorectomy for suspected schwannoma at our Department of Plastic and Reconstructive Surgery. The tumor was 5.0 × 6.0 cm, and it was pathologically diagnosed as malignant meningioma (Fig. A). As metastasis from a primary site was suspected, imaging examinations, including head and neck magnetic resonance imaging and positron emission tomography (PET)-computed tomography (CT) examination, were carried out, but since all were negative, it was diagnosed as ectopic malignant meningioma of the primary axillary soft tissue. After surgery, 50 Gy radiation was locally administered, and she received follow-up outpatient observation. In June 2016, chest radiography showed a nodular shadow in the right lung, so she was referred to our department. There were no notable findings in the laboratory blood test results. Chest radiography indicated a similar circular nodule shadow, 1.1 × 1.0 cm in size, in the right lower lung field. Chest CT showed the 1.0 × 1.0 cm nodule shadow in the right S4; mediastinal and hilar lymph node enlargement was not observed (Fig. B). PET-CT demonstrated slight uptake in the nodule, with a maximal standardized uptake value of 2.94 (Fig. C). There was no evidence of distant metastasis. After the initial examination, it was considered to be a metastatic lung tumor, and we decided to perform surgery as there were no abnormal findings in other organs. Surgery was performed in the left lateral decubitus under differential lung ventilation and 3-port thoracoscopy. There were no adhesions or pleural changes, and the tumor was directly under the right S4 pleura. Thoracoscopic right middle lobe partial resection was performed and the tumor was resected. A diagnosis of meningioma was obtained by intraoperative rapid diagnosis. The operation time was 1 hour, and the bleeding volume was 20 mL. Macroscopically, the tumor, resected from the S4 of the right lung, was 1.3 × 1.0 × 0.8 cm in diameter and a white grayish irregular nodule (Fig. ).
Histologically, the tumor was composed of neoplastic cells with eosinophilic cytoplasm, coarse chromatin, and obvious nucleoli. The histological appearance revealed neoplastic cell proliferation with a whorl pattern, mixed with lymphocyte infiltrate (Fig. A).
Immunohistochemically, some tumor cells were positive for epithelial membrane antigen (EMA) (Fig. B) and estrogen receptor (ER) (Fig. C). The Ki-67 labeling index (LI) was about 40% (Fig. D). MNF116 and S100 staining were negative. Based on these findings, the lesion was diagnosed as lung metastasis of malignant meningioma of the primary axillary tissue. Her postoperative course was uneventful, and she was discharged on postoperative day 4. She has remained healthy without any recurrence 9 months after the lung resection. Informed written consent was obtained from the patient for publication of this case report and accompanying images. |
pmc-6571441-1 | Herein, we reported a case of a 51-year-old woman (parity: 3, labor: 2, delivery: 1), presented with pelvic pain and vaginal bleeding. The pelvic pain was initiated two days before admission and was intensified the morning of hospitalization. The patient had a three-year history of menometrorrhagia, for which she had undergone a diagnostic curettage on August 15, 2016, the pathology of which was reported as "inactive endometrium and endocervical polyp".
Upon admission, the patient’s hemorrhage was similar to menstrual bleeding. In the physical examination, the abdomen was soft with no obvious tenderness. However, on the speculum examination, a circular mass of about 10 cm, similar to a pediculated myoma, was observed in the vagina, extended to the entrance of the vagina during Valsalva maneuver.
Bimanual examination also revealed the occupation of the vaginal space by the mentioned mass, the thick base of which could be touched. However, the uterus was impalpable, and the hemorrhage was analogous to the menstrual bleeding. In an ultrasound performed on April 23, 2016, the uterine size was 56×79×109 mm, and a 55×62 mm intramural fibroid was observed in the posterior wall of the uterus, which pressurized the adjacent endometrium. Moreover, the endometrial thickness was reported to be 7 mm, and the adnexa were normal.
The vital signs were stable on admission; however, the patient looked pale. The patient had a hematocrit level of 24% and a hemoglobin level of 7 mg/dL; however, other tests were normal. To improve the patients' anemia, two units of packed cell were transfused, and the patient was scheduled for surgery.
In the operation room, the patient was put in a dorsal lithotomy position and examined under anesthesia. Due to the lack of access to basic myoma, the patient underwent an abdominal hysterectomy. Her abdomen was opened with a median incision in the area of the previous scar. After opening the fascia and peritoneum and accessing the abdominal cavity, the patient was diagnosed with the uterine inversion based on detecting utero-ovarian round ligament and not observing the fondus ().
At first, it was attempted to treat the inversion through applying tension on the ligament, which was not successful due to the extent of the inversion. Therefore, the utero-ovarian round ligaments were ligated on both sides, and then a longitudinal incision was made on the retraction ring after the lowering of the bladder to reduce the inversion; however, it was not successful. The base of the prolapsed mass was clamped at the incision site, and the mass was driven up into the vaginal canal. Subsequently, the mass was removed by the assistant using tenaculum.
Afterwards, the uterine arteries were ligated on both sides, and a total hysterectomy was performed after obtaining the cardinal and uterosacral ligaments. Subsequently, the myoma and uterus were sent to the laboratory for pathological examination. |
pmc-6571448-1 | The patient was a 34-year-old woman, G4 L2 Ab1 who had married her cousin 7 years ago. She had a history of two normal vaginal deliveries and one abortion in the 1st trimester. The first pregnancy in the age of 28 had terminated with a normal vaginal delivery (NVD) resulting in a term baby girl who weighed 3150 gr. The second pregnancy had occurred two years later; curettage was done at week 6 due to spontaneous abortion. Her 3rd pregnancy was in the age 32 resulting in a healthy term baby girl weighing 3400gr with NVD. Due to her unwillingness for becoming pregnant she had withdrawal contraception, whereas because of the non-occurrence of menstruation during breastfeeding and 6 months after her last pregnancy, a pregnancy test was requested. Due to the positive pregnancy result, ultrasound study was done which revealed a 10-week spontaneous gestation with 4 gestational sacs and 4 fetuses. There was no case of multiple pregnancies in her or her husband's family.
She received prenatal care during her pregnancy but there was no need for prophylactic cerclage. At week 24 of gestation she was hospitalized due to premature contractions. The contractions were controlled with the prescription of pethidine and hydration and she was discharged 3 days later. She was once again admitted at 28 weeks of gestation due to similar contractions; this time she was treated with indomethacin and pethidine and discharged 3 days after the contractions suppression. She also received two doses of betamethasone during hospitalization.
She was admitted a week later due to labour contractions. In vaginal examination 2 finger dilatation with no effacement was detected. Serum test results were reported all in the normal range and the vital signs during hospitalization were normal. At this stage she was treated with tocolytics (adalat). The fetuses' health was monitored by Doppler ultrasound imaging, biophysical profile and fetal non stress test (NST). After the labour contractions' suppression and due to the presence of sporadic contractions she was monitored while being hospitalized up to the time of delivery.
At 32 weeks and 4 days of gestation, due to the resumption of labour contractions and dilatation progression, after receiving the rescue dose of betamethasone, cesarean section and tubectomy (upon the request of the patient and her husband) was performed. The outcome of cesarean section was 4 fetuses, 3 girls and a boy, quadriamniotic and quadrichorionic. Quadruplet A weighed 1820 gram with an Apgar score of 9 to 10; quadruplet B weighed 1810 gram with an Apgar score of 6-7. Quadruplets C and D weighed 2100 and 1980 gram with an Apgar score of 7-8 and 9-10, respectively. Among the 4 neonates, only quadruplet B was transferred to the NICU; she was discharged after 2 days in good health. and show the quadruplets after birth.
Because of atonic uterus during the cesarean section, after the administration of the appropriate dosage of oxytocin and methylergonovine and 800µgr of rectal misoprostol, the uterine arteries were blocked and the B-Lynch suture was done. No blood transfusion was required for the mother and her hemoglobin (Hb) level 6 hours after the operation was 9 g/dl; her pre-operational Hb level was 10g/dl. The mother was discharged 3 days after delivery with no complications.
For close follow up, the mother and her newborns were visited two weeks after delivery; they were all healthy and had no problem. The infants were visited once again 6 months later revealing normal physical and mental development in all four. shows the babies at 6 months of age.
This project has been approved by Ethical Committee and Vice Chancellor for Research of Mashhad University of Medical Sciences (97/429008). |
pmc-6571528-1 | A 13-year-old girl with a 3-week history of headache and reduction in vision was referred to our practice because of possible endocrine problems due to craniopharyngioma. She was the third child of non-related parents. Her birth history was unremarkable. Her height was 150.8 cm [-1.19 standard deviation (SD)] and her weight was 60.2 kg (1.23 SD). Physical examination was normal except for right eye exotropia and accompanying reduction in vision.
No endocrine abnormalities were detected before the craniopharyngioma operation (see ). On the first postoperative day, dexamethasone treatment for brain-associated surgery was started by the neurosurgeon. Therefore no additional steroid treatment was given in case of central adrenal insufficiency. Furthermore, the patient was polyuric (5.6 mL/kg/h), plasma sodium was 146 mmol/L (reference range 135-145), plasma osmolality was 303 mOsm/kgH2O and urinary density was 1002. Desmopressin acetate (0.1 µg/kg/day, melt form) treatment was started for diabetes insipidus (DI). Desmopressin treatment improved her polyuria and plasma sodium concentration. On the fourth postoperative day, levothyroxine (100 µg/day) replacement therapy was started for central hypothyroidism. The patient had also developed hyponatremia, starting on postoperative day four, which gradually worsened. On the fifth postoperative day, urinary output of the patient decreased to 0.7 mL/kg/h. Evaluation of laboratory findings (plasma sodium 128 mmol/L, plasma osmolality 267 mOsm/kgH2O, urinary density 1039) led to the diagnosis of SIADH. Plasma copeptin/ADH levels could not be measured. The findings suggested that SIADH was the second stage of the triphasic condition encountered after cranial surgery. Initial management included fluid restriction (administered fluid: total 800 mL/m2/day) and cessation of desmopressin treatment. Despite fluid restriction for four days, the patient’s blood sodium levels continued to decreas, to 118 mmol/L, and urine density was 1039. Hypertonic saline therapy (3% saline to raise the serum sodium by 10 mEq/L) was also added due to persistence of hyponatremia. However, SIADH could not be controlled and severe hyponatremia continued. In addition, the patient’s condition began to worsen and mild loss of consciousness occurred. Therefore, it was decided to start low-dose oral tolvaptan treatment (0.13 mg/kg/day) on the eighth postoperative day. A written consent form was obtained from the parents for the use of tolvaptan. One hour after oral intake of Tolvaptan, the urine output and plasma sodium levels of the patient began to correct. Urinary output increased to 8.1 mL/kg/h, urinary density reduced to 1001. One dose of tolvaptan administered to the patient was sufficient to control SIADH and no further treatment was given. Moreover, desmopressin treatment was restarted because of the development of DI 42 hours after the administration of tolvaptan (plasma sodium 138 mmol/L, plasma osmolality 296 mOsm/kgH2O, urinary output 6.6 mL/kg/h and urinary density 1002). The patient has had persistent DI on follow up which has required desmopressin therapy (). |
pmc-6571529-1 | A 30-days old infant with a male-dominant genital appearance was referred to pediatric endocrinology because of a uterus, detected on ultrasonography. The infant was born at 23 weeks of gestation by C-section because of preeclampsia and premature membrane rupture. The parents were consanginenous. Birth weight was 680 gr. The infant was intubated, given surfactant treatment and required mechanical ventilation support. Bilateral cryptorchidism and hypospadias were thought to be associated with the severe prematurity. Since gender assessment at birth was made as male, the baby received a male name and identity card. He was the first baby of a 25-year old healthy mother and a 27-year old healthy father who were first cousins. The mother had had two abortions in the past, so she was treated with progesterone for one month between the 16th and 20th gestational weeks and also with salicylic acid throughout the pregnancy. There was no evidence of virilisation, such as acne, hirsutism, deep voice or clitoral enlargement in the maternal history. Physical examination of the infant revealed complete labioscrotal fusion and a single urogenital meatus, consistent with Prader stage-3. Gonads were not palpable, a chorda was present and the phallus was measured as 2x1 cm on the dorsal and 1.6x1 cm on the ventral side. At the time of the investigation the patient was still being followed in the neonatal intensive care unit and having mechanical respiratory support. On postnatal day 30, the patient’s hormone levels were as follows: 17-hydroxy progesterone (17OHP): 41 ng/mL [normal limits (NL) <35.5 ng/mL], DHEA sulphate (DHEASO4): 1500 µg/dL (NL 123-882 µg/dL), testosterone: 2.94 ng/mL (NL 0.05-0.16 ng/mL), FSH: 1.3 IU/L (NL 0.3-2.6 IU/L), LH: 0.48 IU/L (NL 0.1-8.5 IU/L), estradiol <10 pg/mL (NL <15 pg/mL), progesterone: 4.7 ng/mL (NL 0.18-6.4 ng/mL). Karyotype was 46, XX. A standard dose adrenocorticotropic hormone (ACTH) test (30 µg/kg/dose) revealed an inadequate stimulated cortisol and high 17OHP levels, suggesting simple virilising congenital adrenal hyperplasia (CAH) likely due to 21-hydroxylase deficiency (). Additionally there were several other problems, such as septicemia, surfactant deficiency and respiratory distress. The patient was on mechanical ventilation due to severe prematurity at this time. Although the classical findings of adrenal insufficiency were not present, the decision was taken to administer hydrocortisone® replacement since cortisol deficiency could not be excluded. Hydrocortisone® was commenced at a dose of 10 mg/m2/day, three times a day. The name and identity card of the baby were changed to female with the agreement of the parents and the decision of multidisciplinary gender assessment committee.
Over the next two years, androgen levels were quite low, despite hydrocortisone doses as low as 6-7 mg/m2/day, and no mutation in CYP21A2 gene was detected. This unusual clinical condition and lack of a mutation in CYP21A2 gene led to doubt concerning the security of the diagnosis of 21-hydroxylase deficiency. At the age of two years and six months the standard dose ACTH test was repeated, after suspension of hydrocortisone treatment for 48 hours. The results of this test showed the cortisol and androgen levels were normal (). When maternal history was re-evaluated, the mother remembered that she had a mild deep voice during pregnancy. The patient was re-evaluated in terms of 46, XX disorders of sex development (DSD), especially with the suspicion of aromatase deficiency (). Finally, aromatase deficiency was confirmed by genetic analysis ().
At the last clinical visit, the patient was 4.3 years old, height was 95.5 cm (-2.3 SD), weight 14.5 kg (-1.27 SD) and breast development was Tanner stage-1. Further examinations were performed for disorders which could be associated with aromatase deficiency ().
Informed consent was obtained from the parents of the patient for publication of this case.
An Ethylenediaminetetraacetic acid blood sample was taken for CYP19A1 gene sequence analysis. At the PCR step, as the very large region including exon 6 could not be amplified, a long PCR and sequence analysis was planned to detect exact breakpoints. Sequence analysis with a Next Generation Sequencing Method (Illumina-MISEQ, San Diego, CA, USA) was done and a 3212 bp deletion within chromosome 15:51.511.985-51.508.774 was detected (NM_000103.3:c.629-1453_744-486del). This large deletion was evaluated as a likely “pathogenic” variant due to ACMG criteria.
The CYP19A1 gene contains 10 exons and exon 6 was largely deleted with some parts of introns of both sites and two canonical splice sites. This was a null variant. The allele was not found in gnomAD exomes. This is a conserved region in different species. This was a novel variant. |
pmc-6571540-1 | A 20-day-old male infant was referred to our hospital because of hypergalactosemia detected during neonatal mass screening test. He was diagnosed with congenital portal vein hypoplasia and CPSVS. At seven years of age, PAH was found on regular checkup using echocardiography. Continuous intravenous PGI2 (47.2 ng/kg/min) was initiated at nine years of age. The administration of bosentan hydrate (62.5 mg/day) was added at age 10 years. The treatment strategy for his cardiac status was based on World Health Organization (WHO) functional class 2. The right ventricular systolic pressure, estimated from the moderate tricuspid regurgitation, was 80 mmHg on echocardiography. He underwent an assessment of thyroid function once at 16 years of age. The test results showed a low thyroid stimulating hormone (TSH) of 0.04 µU/mL, [reference range (rr): 0.27-4.20] and normal free T4 concentration of 1.42 ng/dL, (rr: 1.00-1.80).
At age 17 years, the patient was admitted to our hospital because of dyspnea, general fatigue and chest pain (WHO class 4). The body temperature was 37.5 ˚C and the heart rate was 120 bpm. On admission, his height was 162.4 cm [-1.1 standard deviation (SD)] and body weight was 44.1 kg (-1.8 SD) resulting in a body mass index of 16.4. Goiter was noted and the liver was palpable at 4.0 cm below the costal margin. Intensified pulmonic sounds with regurgitant systolic murmur was remarkable at the left sternal border. Cardiomegaly was evident on chest radiography. Echocardiography revealed severe tricuspid regurgitation with elevated right ventricular systolic pressure (120 mmHg). A unilateral enlargement of the thyroid gland was detected on ultrasonography with increased blood flow and the estimated thyroid weight was calculated as 3.1 g (right) and 16.7 g (left). Laboratory tests showed a C-reactive protein concentration of 1.8 mg/dL. Brain-type natriuretic peptide was 601.1 pg/mL (cut-off ≤18.4), TSH <0.01 µIU/mL, free T4 at 6.35 ng/dL (rr: 1.00-1.80), thyroid stimulating antibody (TSAb) elevated to 2691% (rr: <180%), TSH receptor antibody (TRAb) level was 10.7 U/L (rr: <1.0 U/L) and thyroglobulin antibody level 1349.7 U/mL (rr: <45 U/L).
Maximum doses of oral thiamazole, potassium iodide and intravenous hydrocortisone treatment failed to control the raging storm of hyperthyroidism. High-dose methylprednisolone therapy and destructive radioiodine (RI) (RI in ) therapy were concurrently initiated on the 88th day of admission. Hyperthyroidism gradually improved after the combined therapy. PGI2 was continued throughout the period of intensive care because PAH had been severe. When PAH started to improve, the estimated right ventricular pressure declined to 70 mmHg. The patient was discharged 132 days after admission (). PAH has been controlled with euthyroid status thereafter. The patient has not received antithyroid therapy for more than four years although TSAb, TRAb and anti-thyroglobulin antibody levels continue to be abnormal. None of his family members were affected by autoimmune thyroiditis. He had no past history of other autoimmune disorders. He had never experienced hypoglycemia, hyperandrogenism or other metabolic attacks before and after this episode.
Written informed consent was obtained from the patient and his parents for the publication of this report.
We performed a literature search for patients under the age of 20 years who presented with hyperthyroidism during treatment with PGI2. We found that 12 such cases had been reported in the years from 2010 to 2017 (,). summarizes the clinical profiles of these 12 cases and compares with data from our patient (case 13 in ). The median (range) age at diagnosis of PAH was 11 (2-17) years, while the hyperthyroidism developed at a median (range) age of 15.8 (6-19) years. Thus, duration to the development of PGI2-associated thyroiditis varied widely from 1 to 11 years after the diagnosis of PAH. Four patients (31%) died of complications including cardiopulmonary dysfunction. We found that six (cases 8-13) among the 13 cases had severe cardiac dysfunction (WHO class 4). Although these six patients underwent thyroidectomy, propylthiouracil or RI therapies, only two (case 12 and the present case) survived the critical period. |
pmc-6571543-1 | The proband was a 2.75 year old child whose social gender was female. The child was taken to our hospital due to absence of vagina. The patient was born full term by spontaneous delivery, and she is the second child of healthy parents of non-consanguineous marriage. Her birth weight was 3,900 g. Her weight at presentation was 17 kg (96.8th percentile) and her height was 97 cm (73.5th percentile). Physical examination showed that the patient exhibited predominantly female external genitalia, with normal bilateral labia majora, bilateral labia minora and external opening of urethra under the clitoris. However, she had a blind-ended vagina without external opening. The patient showed absence of scrotum and penis. Abdominopelvic ultrasound examination detected bilateral testis tissues in the inguinal region (left 2.0 cm×0.7 cm×0.9 cm; right 1.7 cm×0.7 cm×0.9 cm). Uterus or other Mullerian structures were not observed. Laboratory results showed that the patient had extremely low serum testosterone and dihydrotestosterone levels (0.01 nmol/L), which could not be stimulated by hCG. Serum levels of LH and follicle stimulating hormone were within the normal ranges (3.84 IU/L and 9.09 IU/L, respectively) and both of were hyper-responsive (24.48 IU/L and 22.33 IU/L, respectively) to stimulation with 2.5 µg/kg of LH releasing hormone. Thyroid hormones, estradiol, prolactin, blood chemistry and complete blood count were all normal. Primary genetic analysis revealed that the patient’s karyotype was 46, XY and no pathogenic variant was identified in the SRY gene. The patient was primarily diagnosed as a case of male pseudohermaphroditism.
All procedures followed were in accordance with the ethical standards of the responsible institutional committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2000, and the protocol was approved by the Ethics Committee of the First Affiliated Hospital of Xinjiang Medical University (approval no: XJMU-FAHIRB-2017005). Informed consent was obtained from the patient’s family.
To obtain a rapid and accurate clinical genetic diagnosis, trio-whole exome sequencing (WES) was used to screen for causal variants. Briefly, a total of 3 µg of genomic DNA was sheared to obtain DNA fragments with sizes between 150 bp and 200 bp. The capture library was prepared using SureSelect Human All Exon V6 kit (Agilent Technologies Inc., Santa Clara, CA, US) following the manufacturer’s protocol. Next, clusters were generated by isothermal bridge amplification with an Illumina cBot station and sequencing was performed by an Illumina X10 System (Illumina, CA, USA). Alignment of sequence reads to the reference human genome (Human 37.3, SNP135) was performed using the NextGENe® software (SoftGenetics, PA, USA). All single nucleotide variants (SNVs) and indels were saved in a VCF format file, which was then uploaded to Ingenuity® Variant Analysis™ (Ingenuity Systems, CA, USA) for biological analysis and interpretation. The variants were validated by Sanger sequencing using the ABI3730XL sequencer (Applied Biosystems, Thermo Fisher Scientific, Inc., Waltham, MA, USA) with the forward and reverse primers. The potential pathogenicity of the missense variant was analyzed by using MultAlin (http://multalin.toulouse.inra.fr/multalin/), PolyPhen-2 (http://genetics.bwh.harvard.edu/pph2/), Combined Annotation Dependent Depletion (CADD) (http://cadd.gs.washington.edu/), and MutationTaster (http://www.mutationtaster.org/).
For the patient, WES yielded a total of 103,509,228 reads, and the mean target coverage was 133 reads with 95.52% having 20× coverage and 99.83% having 1× coverage. The candidate variants were first filtered by the following parameters: () minor allele frequency (MAF) under 1% in genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/); () the benign variants, including synonymous and harmless missenses predicted by Ingenuity and those predicted to have no impact on splicing by MaxEntScan. Subsequently, clinical symptoms of male pseudohermaphroditism were used as filtering indexes to analyze the candidate variants. As a result, we identified a compound alteration with two heterozygous variants within the LHCGR gene, which we believe to have contributed to the patient’s condition. Of the two variants, one is a novel missense variant in exon 4 (c.349G>A, p.Gly117Arg), and the other was a novel nonsense variant in exon 10 (c.878C>A, p.Ser293*). We have further confirmed the compound heterozygous variants by Sanger sequencing. The patient’s father was heterozygous for the nonsense variant and the patient’s mother was heterozygous for the missense variant ().
To evaluate the pathogenicity of the novel variant c.349G>A, we first analyzed the conservation of Gly117 using MultAlin software. As shown in , results from MultAlin show that the amino acid glycine at codon 117 is highly evolutionarily conserved. Next, we used three in silico prediction software analyses to evaluate the impact of the variant on protein function. The PolyPhen-2 score of the variant is 0.96, indicating that the variant is probably damaging. The MutationTaster score is 1, which implies that the variant is likely disease causing. The CADD score is 25.4, which suggests that the variant can be damaging. To better understand the missense variant, the WT and variant amino acid at codon 117 were modeled into the three-dimensional structure of the LHCGR protein () (). Based on the structure () and domain information of the LHCGR wild-type protein obtained from Uniprot (http://www.uniprot.org/), the amino acid substitution at the 117th position (p.Gly117Arg) was predicted to disrupt the first LRR domain, which may affect recognition and binding affinity of LHCGR to hCG and/or other ligands. Taken together, our analysis results indicate that the c.349G>A (p.Gly117Arg) variant is likely harmful to the protein function. |
pmc-6571568-1 | Patient 1 (gold mining region of the União do Norte district, Peixoto de Azevedo in northern Mato Grosso):
In June 2015, a 37-year-old male patient presented to a public hospital with a history of fever, headache, and myalgia; he was treated and released with suspected dengue. Four days later, the patient presented with dyspnea, acute respiratory failure, blurred vision, and chest pain, and was referred to the intensive care unit (ICU), where treatment included the use of antibiotics and a mechanical respirator. His nonspecific tests showed increased urea and creatinine (127.40 mg/dL and 2.42 mg/dL, respectively), thrombocytopenia (58,000/mm3), and leukocytosis (20,040/mm3). A chest radiograph confirmed a pulmonary diffuse interstitial infiltrate (). On the sixth day of the disease, with suspected HPS, a blood sample was collected, of which the serological analysis confirmed the presence of anti-hantavirus IgM antibodies with negative IgG []. Hantavirus genome was detected in a blood sample using reverse transcription polymerase chain reaction (RT-PCR), and the genotype identified was Castelo dos Sonhos virus []. Despite the measures imposed in the intensive care unit, the patient progressed to death three weeks after the onset of illness. The patient was a machine operator in a gold mine and lived in Sinop, a municipality in the Legal Amazon region in Mato Grosso state. |
pmc-6571568-2 | Patient 2 (gold mining region of the União do Norte district, Peixoto de Azevedo in northern Mato Grosso):
A 47-year-old man with fever, headache, myalgia, chest pain, dry cough, dizziness, asthenia, dyspnea, acute respiratory failure, and back pain was admitted to the same public hospital as Patient 1 in June 2015. The laboratory test revealed hemoconcentration (47.1%), thrombocytopenia (37,000/mm3), leukocytosis (22,180/mm3), increased urea and creatinine (72.56 mg/dL and 1.87 mg/dL, respectively), aspartate aminotransferase (102.4 IU), and alanine aminotransferase (57.14 IU). Chest X-ray was not performed. The analysis of the serum sample collected on the seventh day of the disease showed the presence of anti-hantavirus IgM antibodies, with negative IgG, but detected hantavirus Castelo dos Sonhos by RT-PCR. Although a therapeutic strategy based on antibiotics associated with hemodynamic and respiratory support was followed, the patient died nine days after the onset of the illness.
After the first occurrence of HPS in miners, a study was carried out to estimate the prevalence of anti-hantavirus antibodies in 112 samples previously collected from a population living in a mining area in the Três Fronteiras district in the city of Colniza, Mato Grosso (). These serum samples, which were stored in the Malaria Biorepository of the University Hospital Júlio Muller following a malaria survey conducted in 2012, were used due to the physiogeographical and population similarities between this gold mining area and the area where the two fatal HPS cases were identified. These two mining areas, even if geographically distant, are comparable because they are located in the Amazon biome, have the same environmental modifications from the garimpo and the populations have similar income, housing and access to health.
The data were collected in July 2012 from 112 Igarapé Grande gold mining and São Francisco gold mining, municipality of Colniza, this number represents all inhabitants of the mining areas mentioned above. This data included collection of blood samples using the finger prick and thick smear technique, completion of the SIVEP-Malaria notification form, and completion of an interview to obtain demographic and socioeconomic information and information about exposure to malaria transmission.
The serum samples from human cases of HPS and cohort were tested by anti-hantavirus IgG and IgM antibodies screening, using the recombinant N protein of Araraquara virus, provided by the University of São Paulo/Ribeirão Preto [], following the protocols of enzyme immunoassays ELISA. This antigen is representative for all genotypes isolated in Brazil.
The malaria incidence in the population of miners in Colniza in 2012 was 4.46% (4 cases of Plasmodium falciparum and one of P. vivax), whereas the hantavirus seroprevalence was 3.57%, with four reactive IgG samples, all negative for IgM antibodies. One of the four hantavirus seropositive patients, in addition to mentioning an unspecific fever history on the day of data collection, also presented positive results in a thick blood smear for malaria with the identification of P. falciparum.
For demographic data, among the 112 study participants, 56.25% were men. Nevertheless, when evaluating the four hantavirus seroreactive patients, three were women. The age of the study population ranged from six months to 65 years, with an average of 29 years. It is noteworthy that one of the 48 women was pregnant. The predominant color was pardo in 68.8% of the general population and 50% of the seroreactive population, while 41.1% of the study population were married and another 41.1% single, see .
Regarding educational attainment, shows that all seropositive patients and 75% of the total attended school. Vegetal exploration (18.75%), which include professional activities that involve explorations of the environment, and housewife (12.5%) were the most common occupations, but 64.4% of the respondents mentioned other types of employment related to mining activity. The most common housing type was wooden houses, in addition to seven houses built from canvas. Eight interviewees reported information collected on clinical aspects, and one hantavirus seroreactive individual reported fever, headache, and body pain, see . |
pmc-6571633-1 | A 49-year-old woman was admitted to Vilnius University Hospital Santaros Klinikos cardiology unit due to progressive dyspnea, reduced physical activity, and periodic cardiac arrhythmia. A full cardiovascular examination was performed.
Analysis of medical history revealed that during childhood the patient suffered from acroparesthesia, heat intolerance, and severe abdominal pain with gastrointestinal abnormalities such as diarrhea and constipation. Bronchial asthma had been diagnosed and experienced since her adolescence. She had been followed by a nephrologist since the age of 20 because of recurrent pyelonephritis, acute urinary tract infections, subnephrotic proteinuria (<1 g/L) and edema in her lower limbs. Glomerulus filtration rate was normal. Kidney ultrasound showed no changes. At the age of 39 palpitations of the heart, dyspnea, reduced physical activity, and low blood pressure were noticed. At the same age, she manifested episodes of tinnitus, hearing impairments, and some angiokeratoma in the umbilical region.
During evaluation in our center, her electrocardiogram (ECG) showed normal sinus rhythm, short PR interval, as well as signs of left ventricular (LV) hypertrophy with secondary repolarization abnormalities. Echocardiography revealed asymmetric myocardial hypertrophy in the LV apex and in the lateral wall without LV outflow tract obstruction. Two-dimensional strain analysis showed a reduced global longitudinal strain (GLS−14%), especially reduced in the posterolateral wall (peak systolic strain−8%), whereas diastolic function of the LV was normal. Cardiac magnetic resonance imaging (MRI) also showed an asymmetric myocardial hypertrophy which was most significant in the apex and the lateral wall of the LV. Gadolinium enhancement imaging did not disclose any fibrotic alterations of the myocardium.
Given the clinical suspicion of Fabry disease, the patient underwent complete diagnostic workup which revealed specific ophthalmological findings (cornea verticillata) and mild proteinuria without signs of renal failure. Brain MRI on T2/FLAIR revealed white matter hyperintensities lesions while no other findings including ischemic or vascular abnormalities were observed. Color Doppler of the extracranial arteries showed normal carotid diameter with no occlusions or vasospasm. Electroneurography of upper and lower extremities revealed ordinary amplitude and conduction of motor nerves with no signs of polyneuropathy.
Considering all clinical manifestations, Fabry disease was suspected and genetic and enzymatic analyses were thus performed. Peripheral blood samples were collected and DNA was extracted using the GenElute Blood Genomic DNA Kit (Sigma-Aldrich, USA). The GLA gene was analyzed by PCR and sequencing of the entire coding region and the highly conserved exon–intron splice junctions was performed. The concentration of the biomarker lyso-Gb3 in a dried blood spot was measured using HPLC and tandem mass spectrometry. The patient’s GLA gene sequencing analysis revealed a heterozygous mutation in exon 2 of GLA, c.270C>G (p. Cys90Trp). It is located in a weakly conserved nucleotide and highly conserved amino acid position, with large physicochemical differences between the exchanged amino acids (Alamut v.2.7.1) (). The concentration of the biomarker lyso-Gb3 was pathologically increased to 10.0 ng/mL (reference: ≤1.8 ng/mL).
Since a previously unreported mutation was detected, a kidney biopsy was performed on the proband to support the diagnosis, in which ultrastructural pathognomic changes consistent with Fabry disease were found (). Light microscopy examination showed enlarged podocytes with foamy vacuoles. Electron microscopy identified typical electron-dense multilamellar inclusions and zebra bodies in the cytoplasm of podocytes as well as focal podocyte foot process effacement.
Once the diagnosis of Fabry disease was confirmed, genetic analysis was extended to the family members of the patient (mother, two sons, and her brother) (). The sequence analysis of the GLA gene showed that the patient’s 70-year-old mother was heterozygous for c.270C>G (p. Cys90Trp) mutation. The concentration of the lyso-Gb3 biomarker was pathologically increased (13.4 ng/mL). She was diagnosed with HCMP and suffered from heart failure. Since she had experienced syncope and life-threatening ventricular arrhythmia, a cardioverter-defibrillator had been implanted. Fabry disease was also confirmed in one of the patient’s sons by measurement of leukocyte α-galactosidase A activity (0.8 (limit of detection) µmol/L/h (reference ≥15.3 µmol/L/h)) and DNA analysis. The concentration of the biomarker lyso-Gb3 was significantly increased (98 ng/mL). The 25-year-old son revealed clinical manifestations referable to Fabry disease such as severe acroparesthesias, anhidrosis, heat intolerance, clustered angiokeratoma on the thighs, tinnitus, abdominal pain, diarrhea, as well as depression and specific ophthalmological findings (cornea verticillata). The results of the blood and urine analysis were in the normal range. His kidney ultrasound and brain MRI showed no changes. Echocardiography revealed heart morphology and function to be normal. Electrocardiography showed electrical left-ventricle hypertrophy (LVH).
Both the proband and her son were referred for ERT treatment a year following diagnosis. agalsidase alfa was given at 0.2 mg/kg body weight every other week by intravenous (IV) infusion. Regular assessments of the impact of ERT on all affected organ systems were performed according to Fabry disease recommendations []. The mother had significant improvements of her cardiac symptoms, while her son experienced marked clinical beneficial effects on acroparesthesias and all manifestations due to early diagnosis and management of Fabry disease according to the literature []. Better responses to treatment in decreasing lyso-Gb3 from baseline 92.1–39.7 to 30.4 ng/L (reference value <1.8 ng/L) after two years of initiating ERT was observed in the proband’s son compared with his mother (8.9 ng/L–8.7 to 10.5ng/L). The patient’s mother was not treated with ERT due to her age and late diagnosis, since there is no clinical evidence for its effectiveness, and the benefit for the elderly is doubtful in terms of life expectancy and cost effectiveness. Decision to treat can be influenced by advanced elderly age of the patients and severe comorbidities []. The summary of clinical and pathological findings and treatment of the patient and her family members is shown in . |
pmc-6571665-1 | The patient, a 42-year-old man, seeking a vasectomy operation, was consulted by a urologist. The patient did not have any symptoms specific to the urogenital system. The ultrasound scan showed a 2.1 × 2.2 cm hypoechogenic, hypervascular tumor in the middle third of a left testicle (). Previous cryptorchidism was not reported. The patient had had a testicular trauma 3 months before. The family history was negative for any neoplasms. There were no physical signs (i.e., gynecomastia, etc.) of a hormone imbalance observed. Serum cancer markers (α-fetoprotein, alkaline phosphates, β-human chorionic gonadotropin, and lactic dehydrogenase) were all within the normal range. As diagnosis was not clear, it was decided to perform a rapid microscopic evaluation. Rapid microscopic evaluation of fresh frozen sections during the operation was inconclusive; hence, a radical orchiectomy was not performed immediately. On formalin-fixed paraffin-embedded (FFPE) sections, the tumor histology showed atypical patterns, and immunohistochemical analysis was performed in order to determine the type of neoplasm and differentiate it from other types of testicular tumors so as to assign the further course of treatment. A full-body CT (computed tomography) scan showed no evidence of metastatic disease; thus, a radical inguinal orchidectomy was performed. The gross examination found the tumor to be of similar color to the rest of the testicular tissue but of firmer texture. Histological analysis revealed that tumor had a biphasic structure () and was composed of a hypocellular collagenous stroma and solid nested serpentine trabecular structures (with small scant tubule formation and lumina containing homogeneous eosinophilic secretion ()) from small to medium size cells with pale eosinophilic, finely vacuolated cytoplasm, and evenly centered round nuclei with a small peripheral nucleolus, finely dispersed chromatin, and unidentifiable mitotic activity. Usually, when an indolent epithelioid testicular tumor (most probably primary) is discovered in a middle-aged patient, the sex cord–stromal tumor group is the first one to turn to; therefore, an initial array of immunohistochemistry stains (based on WHO classification) was ordered. The tumor showed positive for Beta-Catenin () and CD99 (); Ki67 () proliferative activity was very low ~1% (0.987% using Aperio “Nuclear v9” algorithm). As CD99 was the only typical positive “sex cord” marker, additional stains were ordered to clarify the case and exclude other malignancies (see ).
In conclusion, the histologic pattern and the immunophenotype are not entirely typical but most closely resemble a Sertoli cell tumor. Permission was issued by Vilnius City Clinical Hospital of Medical Ethics Commission (Nr. V6-4, 2019-03-02). Informed consent was obtained from the participant. |
pmc-6571741-1 | This case concerns a 27-year-old female patient with two previous pregnancies—a tubal pregnancy, which ended in a laparoscopic left-sided salpingectomy, and an intrauterine pregnancy, which ended in the parturition of a full-term newborn after cesarean section. The patient was admitted as an emergency case—hemodynamically stable, with a severe, piercing pain in the lesser pelvis, positive Blumberg’s sign, and echographic data of hemoperitoneum. The patient reported a positive urine pregnancy test, according to the term of amenorrhea in 7.2 gestational weeks, while hyperplastic endometrium of 14 mm was visualized by the vaginal echography performed without presence of an intrauterine pregnancy. The laboratory parameters at the time of admission were as follows: hemoglobin—127 g/L, hematocrit—0.374 l/L, β-human chorionic gonadotropin (β-HCG)—9957.96 mIU/mL.
Emergency mini-laparoscopy was performed in view of the imaging and clinical data of disturbed EP and hemoperitoneum. Massive hemoperitoneum was found with the presence of sanguineous coagulums in the lesser pelvis, lateral paracolic gutters, and domes of the diaphragm.
When performing the intervention, we used 2.6 mm, 30° optics (LIL-33-30, Microlap, Conmed, Utica, NY, USA), with one 3 mm port (Microlap, Conmed, Utica, NY, USA) for micro-laparoscopic instruments and one 10 mm port for evacuation of decidual portions and sanguineous coagulums, and insertion of a needle and 15 mm, 2-0 V-Loc™ suture. A set of instruments was used for mini-laparoscopy (Microlap, Conmed, Utica, NY, USA). The operative access was realized with a Veress needle in the base of the umbilical ring.
Active arterial bleeding from a rupture of interstitial pregnancy was found in the area of the left uterine horn, at the site of a previous salpingectomy. Coagulation was performed and hemostatic suture was placed ().
Decidual portions and sanguineous coagulums were evacuated, and lavage and drainage of abdominal cavity were performed. A cyst of yellow body was visualized in the left ovary. No pathological changes were found in the right uterine tube or uterus. The duration of the operative intervention was 65 min, and there were no complications during its course. Hemotransfusion of one unit of red blood cell concentrate was realized in the early postoperative period; it was implemented due to the measurement of a reduction in the preoperative hemoglobin with 45 units at post-surgery hour 4. The abdominal drain was patent, but there was no demonstration of active bleeding. The patient was discharged on post-surgery day 3 in a good general condition with the following laboratory parameters: hemoglobin—86 g/L, hematocrit—0.265 l/L, β-HCG—2925 mIU/mL.
Positive results of β-HCG were not found in a blood sample one month later. The surgical wounds healed by first intention.
Four months after the intervention was performed, an intrauterine pregnancy was found, with a cyst of yellow body in the right ovary; at present, it is following a course with no complications.
The patient signed the consent for publication. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Acibadem City Clinic Hospital “Tokuda” under 22.03.2019/№22. |
pmc-6571850-1 | A 68-year-old man presented with a ten-year history of a lump in the right nasal tip, with a significant increase in size over a six-month period. Medical history included adenocarcinoma of the rectum treated with surgery and radiotherapy two years previously, polycythaemia, chronic alcohol abuse and a 50-pack per year smoking history. Clinical examination revealed a large bulbous firm swelling of the right lower third of the nose causing significant cosmetic asymmetry and distorting the right ala (). Rigid nasal endoscopy was otherwise unremarkable, and oropharyngeal and neck examination was normal. Computed tomography (CT) scan showed a 2.8 cm soft tissue lesion arising from the right anterior nares, abutting but not obviously involving the cartilaginous septum. Magnetic resonance imaging (MRI) confirmed a right-sided 3.4 cm mass arising from the lower lateral alar cartilage () with no apparent invasion of the nasal septum or adjacent soft tissues. An incisional biopsy via the vestibular aspect revealed a well-defined avascular mass with a lobulated surface. The initial histopathological report was suggestive of benign enchondroma, however further review considered low-grade chondrosarcoma to be more likely. Imaging of the neck and chest showed no evidence of metastatic disease, but two small lung nodules were identified, with a subsequent diagnosis of primary adenocarcinoma of the lung.
After discussion at the multidisciplinary head and neck meeting, the patient underwent primary resection via an external rhinoplasty approach. The skin and soft tissue envelope (SSTE) was not adherent to the tumor, which was well-circumscribed and easily dissected from the surrounding soft tissue with no evidence of local invasion. Macroscopic resection of a 3 cm × 3 cm × 3 cm mass arising from the lateral crus of the right LLC was performed ( and ). Soft tissue superficial to the tumor and the right upper lateral cartilage were excised as margins. Primary reconstruction of the LLC was performed using native septal cartilage harvested through a separate left Killian’s incision. A lateral crural strut graft was sutured to the preserved dome of the native LLC medially and placed into a soft tissue pocket laterally (). Silastic splints were placed on either side of the right ala to minimize the dead space left after resection of the tumour (). An external plaster of Paris splint was also applied.
Histopathological review of the specimen confirmed an intermediate grade chondrosarcoma with clear resection margins. As the tumor was resected from an easily observable area, the multidisciplinary head and neck meeting recommendation was for surveillance only, with no postoperative radiotherapy at this stage.
There were no post-operative complications. Sutures and splints were removed one week following surgery. The SSTE was contracted and adhered to underlying tissue without development of seroma or haematoma. At five-week review, the right nasal airway was patent with no dynamic collapse of the right nasal ala. At four months (), there was no evidence of locoregional disease and the patient’s right nasal airway remained patent (). The patient is due to undergo radiotherapy for the lung cancer diagnosed on his staging CT scan. |
pmc-6572170-1 | A 77-year-old man, previously healthy, presented to the emergency department because of urinary retention, weakness and paresthesia of both lower limbs. The history went back to two weeks prior to presentation, where he started to complain of paresthesia and paresis of his right lower limb. The symptoms were of insidious onset and rapidly progressed to involve both lower limbs. The history was also marked by a zoster rash which appeared 10 days prior to the onset of neurological symptoms and involved the right L4–L5 dermatomes.
Upon admission, neurological exam revealed severe weakness of the lower limbs (medical research council (MRC) grade 0/5) and normal muscle strength of the upper limbs. Ankle and knee jerk reflexes were abolished bilaterally, and Babinski sign was found bilaterally. Furthermore, decreased sensation to touch was noticed with T2 sensitive level bilaterally. Vibration, temperature and pinprick sensations were also diminished in lower limbs. The remaining neurological functions were unremarkable.
Magnetic resonance imaging (MRI) revealed a hyperintense T2 lesion in the spinal cord extending from T2 to T11 (A,B) with gadolinium enhancement on T1 sequence observed at the level of T7–T8 (C). No brain or optic nerves lesions were found.
Laboratory tests revealed elevated white blood cells (WBC = 14100, 72% PMN) and positive IgG VZV serology. IgM VZV serology was negative. Other viral and bacterial serologies (Hepatitis B and C, HIV, CMV, HSV, Lyme disease and syphilis) were negative. Auto-immune and vitamins workup was unremarkable.
Cerebrospinal fluid (CSF) testing showed lymphocytic pleocytosis (94 cells/uL) and elevated VZV IgG (0.88) with a high VZV IgG index (14). The remaining tests (VDRL-TPHA test, Wright test, gram testing and bacterial cultures) were negative.
From these data, the diagnosis of VZV-induced LETM was made. Thus, the patient was treated with intravenous (IV) acyclovir (700 mg every 8 h (10 mg/kg)) for 21 days and methylprednisolone 1 g/day for three days followed by oral tapering. These treatments did not allow any clinical amelioration. Therefore, a five-day course of plasma exchange was performed and yielded unsatisfactory outcomes. An MRC grade of 1/5 muscle strength in lower limbs was achieved and sphincter dysfunction did not improve. The patient remained clinically stable without new manifestations for at least one year later (i.e., last follow-up). |
pmc-6572291-1 | A 40-year-old Caucasian male presented with painless jaundice and two-month history of bowel irregularity. The patient described loose stools, increasing in frequency over a two-month period, which floated and were difficult to flush. Past medical history is remarkable for a 14-year history of ulcerative colitis (UC), in remission, and Primary Sclerosing Cholangitis (PSC). At the time of presentation, the patient was two years post orthotopic liver transplant with curative intent for end stage liver disease secondary to rapid progression of his PSC. The patient tolerated the transplant well without acute rejection or infective complications. His medications included tacrolimus and prednisone. A routine abdominal ultrasound identified an irregular mass in the pancreas that led to additional imaging studies, including an abdominal computed tomography (CT). The abdominal CT with contrast identified a large, bulky, poorly delineated mass in the head of the pancreas. The mass was found to be invading segment 1 and 2 of the duodenum and obliterating the common bile duct. CT thorax and pelvis did not report metastatic disease. Magnetic resonance study confirmed locally advanced disease, deemed to be borderline resectable at initial presentation. An endoscopic ultrasound guided biopsy confirmed poorly differentiated adenocarcinoma of the pancreas. At this time, the case was reviewed by the multidisciplinary team and treatment options were presented to the patient. The patient, understanding the gravity of the diagnosis, wished to pursue maximal therapy and undergo neoadjuvant FOLFIRINOX followed by reassessment for potential curative resection. This triggered referral to our Personalized Medicine Clinic for DPYD genotype testing, the patient was genotyped using DNA from PBMCs and found to be wild-type for the following DPYD SNPs c.1905+1G>A, c.2846A>T, c.1679G>T, and c.1236G>A, tested in accordance with the CPIC guideline []. However, it was identified that given the patient’s history of orthotopic liver transplant of unknown DPYD status, there would be limited value in the genetic background of his PBMCs. Therefore, the treating medical oncologists proceeded with an initial dose reduction of 30% as a way of balancing the patient’s desire for maximal therapy and the care team’s desire to prevent early severe toxicity in this unknown setting.
We planned to employ TDM utilizing liquid-liquid extraction and a high-pressure liquid chromatography tandem mass spectrometry assay developed in our laboratory for research purposes, to verify the patient’s systemic exposure was below the toxic threshold. Accordingly, for the first treatment of FOLFIRINOX, the patient received a 30% dose reduction of the 5-FU components. During the continuous infusion of 5-FU, a peripheral whole blood sample was collected from a venous puncture contralateral to the 5-FU infusion site. The sample was collected 2 h post initiation of the 5-FU continuous infusion pump. The sample was immediately placed on ice and the plasma was separated by centrifugation within 20 min at which time it was frozen to −80°C. We determined the patient’s plasma concentration of 5-FU to be 204.97 ng/mL, given a 46-h infusion this equates to an area under the curve of 9.43 mg·h/L, considered to be a subtherapeutic concentration. Combined with clinical observation of the patient, this result provided reassurance that the patient was not demonstrating signs of frank DPD deficiency. The treating oncologist utilized these results and titrated the dose accordingly while using published titration algorithms for reference [,]. The patient was keen to proceed to full dose intensity and the treating oncologists elected to administer the full dose of 5-FU with the reassurance of the TDM. To ensure this was an appropriate course of action and the transplant liver responded appropriately to the larger dose, we continued to monitor the patient. During the second cycle the patient was seen 24 h into the infusion instead of 2 h into continuous infusion as in the first cycle. Despite the known intra-patient variation changing the time of sampling was required to accommodate the logistics of this patient. The decision was deemed appropriate as the measurement would be at the predicted peak systemic 5-FU level and still serve to prevent supratherapeutic dosing. During the second infusion we found the patient’s plasma concentration of 5-FU to be 539.04 ng/mL, equating a predicted AUC of 24.8 mg·h/L. This falls directly within the known therapeutic range of 5-FU and provided confidence to the treating physician that the patient was now receiving optimal management with regards to the 5-FU component. The patient continued with FOLFIRINOX therapy, without developing any severe fluoropyrimidine-related AEs. Following this neoadjuvant course there was significant disease response and the patient proceeded to surgery with curative intent. |
pmc-6572507-1 | The patient is a 62-year-old woman who was brought to the emergency department (ED) with 2 episodes of sudden onset substernal chest pain, each episode lasting for 30 min. Her chest pain had resolved at the time of arrival. Prior to that, she had felt nauseous which was usual for her after her chemotherapy. Chest pain was followed by right-sided, sharp diffuse abdominal pain which lasted for 10 min and resolved spontaneously. She had received her last chemotherapy infusion 2 days prior to the episode. She denied any fever, chills, cough or shortness of breath. She was diagnosed of NSCLC with bone metastases (epidermal growth factor receptor negative and PD-L1-80%) a year ago for which she underwent radiation therapy of left hip and right upper ribs, completed palliative chemotherapy with 6 cycles of pemetrexed 500 mg/m2/dose, carboplatin 550 mg, and pembrolizumab 200 mg followed by same doses of pemetrexed and pembrolizumab maintenance every 3 weeks with last dose 2 days prior to presentation. The patient had been on pembrolizumab for 6 months prior to the decline in renal function. Other past medical history included stage IA right breast cancer (estrogen receptor+ (90%), progesterone receptor+ (3–5%), and human epidermal growth factor receptor 2-negative invasive ductal carcinoma) for which she underwent a bilateral mastectomy, 6 cycles of cyclophosphamide, methotrexate, and fluorouracil, and tamoxifen for 5 years 20 years ago, hypothyroidism, and hyperlipidemia. Her home medications included levothyroxine 75 µg daily, folic acid 1 mg daily, pantoprazole 40 mg daily, rosuvastatin 5 mg nightly, dexamethasone 8 mg two doses before and after chemotherapy, olanzapine 10 mg nightly, lorazepam 0.5 mg as needed, ondansetron 8 mg as needed, prochlorperazine 10 mg as needed, and promethazine 25 mg as needed. She had smoked a pack a day for 15 years before quitting 27 years ago.
On examination, vitals were stable with a temperature of 36.7 °C (98.1 °F), blood pressure 139/82 mm Hg, pulse 79 beats per minute, respiratory rate 18 breaths per minute, and she was maintaining saturation on room air. Chest, cardiac, and abdominal examinations were unremarkable. Her hemoglobin was 9.1 g/dL (reference range: 12.0–16.0 g/dL), platelet count was 556,000/µL (reference range: 13,000–400,000/µL), and white count was 10,700/µL (reference range: 4800–10,800/µL) with neutrophil count of 9800/µL (reference range: 2000–8000/µL), monocyte count of 400 (reference range: 100–1300/µL), and immature granulocyte count of 260/µL (reference range: 0–30/µL). Serial troponins and electrocardiograms were non-suggestive of an acute coronary syndrome. Her creatinine was 1.69 mg/dL (reference range: 0.6–1.3 mg/dL). It was 1.72 two days prior above her baseline of 0.6–0.9. Although d-dimer was 1.02 (reference range: <0.53 µg/mL), computed tomography (CT) pulmonary embolism protocol was not done as ultrasound lower extremity vein bilateral was negative and there was low clinical suspicion for pulmonary embolism. CT without contrast of chest/abdomen/pelvis showed decreasing right upper lobe mass and surrounding consolidation. She had bilateral enlarging metastatic lung nodules. Hepatic metastases were not identified but contrast was not used. Bone metastases were unchanged. Her kidneys and urinary tract on CT and urinalysis were unremarkable. Her acute kidney injury (AKI) was thought to be related to poor oral intake and vomiting related volume depletion. The patient was discharged home and was recommended hydration and repeat labs in a few days. Her creatinine on the day of discharge was 1.83 mg/dL.
Two days post discharge, the patient called her oncologist and told that she had started feeling sick on the same day after she was discharged. She complained of fever with maximum recorded temperature was 102.7 °F along with chills and rigors. She had multiple episodes of vomiting and poor intake. She was directly admitted to the hospital. At presentation, her vitals were stable with a temperature of 37.0 °C (98.6 °F), blood pressure 140/71 mm Hg, pulse 84 beats per minute, and respiratory rate 20 breaths per minute. Chest, cardiac, and abdominal examinations were unremarkable. Her mucous membranes were moist. Her hemoglobin was 8.2 g/dL (reference range: 12.0–16.0 g/dL), platelet count was 257,000/µL (reference range: 13,000–400,000/µL), white count was 2600/µL (reference range: 4800–10,800/µL) with neutrophil count of 1500/µL (reference range: 2000–8000/µL), monocyte count of 0/µL (reference range: 100–1300/µL), and immature granulocyte count of 50/µL (reference range: 0–30/µL). Her low cell counts were thought to be related to her chemotherapy. No eosinophilia was noted in complete blood count during hospitalization or prior to presentation. Her urinalysis was negative for infection but showed 30 mg /dL (1+) proteinuria. Her blood and urine cultures showed no growth. Her creatinine was elevated at 3.70 mg/dL and this was again thought to be related to volume depletion. The patient was started on intravenous fluids. Her renal ultrasound was unremarkable. With suspicion for pembrolizumab as a potential cause for acute kidney injury, future infusions were held. The patient was given a dose of IV methylprednisone 80 mg (1 mg/kg) and planned to be started on prednisone 80 mg daily next day. She was planned for a renal biopsy to rule out medication-related injury. Her creatinine progressively improved during her 5-day-stay and was 2.10 on discharge. We think this was with discontinuation of pembrolizumab. Her renal biopsy showed evidence of acute tubular injury, focal interstitial inflammation (lymphocytes, plasma cells, few eosinophils, few neutrophils) with focal mild tubulitis, 14% globally sclerotic glomeruli, mild arterial thickening, and mild interstitial fibrosis (). This was thought to be secondary to pembrolizumab which was permanently discontinued. She was started on docetaxel 125 mg every 3 weeks. She has received 3 cycles so far. With non-improvement in kidney function, prednisone dose was increased to 1 mg/kg/day (70 mg) for a course of 3 months. Sulfamethoxazole-trimethoprim and pantoprazole were started for prophylaxis. Her creatinine even after 5 months is still elevated. Her new creatinine baseline is around 1.8–2.0. Pertinent case details are summarized in . |
pmc-6572536-1 | A seven-year-old male patient applied with an unbalanced walking complaint. Ten days earlier he was diagnosed with hepatitis A and had jaundice. The patient had no other important details in his medical history. Bilateral peripheral facial paralysis and ataxia were detected on physical examination ().
Of all muscle groups, lower limb muscle power was 4/5. Bilateral lower extremity deep tendon reflexes were decreased. There was no bowel or bladder involvement.
Blood tests were performed to examine full blood counts, electrolytes and urea, and all were within the reasonable limits. Magnetic Resonance Imaging (MRI) scan of the head did not reveal any pathology. Cerebrospinal fluid (CSF) examination showed a high protein concentration (146.9 mg/dL, standard 45 mg/dL), with no white blood cells. Nerve conduction studies (NCS) revealed marginally undetected tibial F-waves and sensory neuropathy with a decrease of sensory nerve action potentials of the sural and median nerve accompanied. Median and peroneal nerve combined muscle action potential (CMAP) amplitudes were absent. Intravenous immunoglobulin (IVIG) treatment was given with a dose of 2 g/kg for five days. Respiratory distress and hypertension developed on the second day of admission, and the patient had a mechanic ventilation requirement. Plasma exchange was performed every other day, and total of three times. The patient’s facial paralysis and ataxia partially regressed 14 days after onset, and disappeared completely after 23 days. There has been no proof of recurrence one year later. |
pmc-6572536-2 | A six-year-old boy was brought to the emergency department with a complaint of difficulty walking after five days of an upper respiratory tract infection. On the physical examination, bilateral peripheral facial paralysis was seen (). Muscle strength of bilateral limbs were 3/5, and arms were 4/5. Deep tendon reflexes on bilateral limbs were hypoactive.
Hemogram, serum biochemistry, and potassium test were regular, serology for antinuclear antibody (ANA), hepatitis B surface antigen (HBsAg), and human immunodeficiency virus (HIV) were negative. In the examination of CSF, CSF protein was 85 mg/dL, and 4/mm3 lymphocyte was found in the CSF. In electrophysiological studies, sensory nerve conduction studies were normal. Median, ulnar and peroneal nerve CMAP amplitudes were absent. Posterior tibial nerve CMAP amplitudes were decreased, distal motor latency and motor conduction velocities were normal. IVIG was given with 2 gr/kg/day dose for two days. Three days after the hospitalization, rapid progressive paralysis developed at all four extremities, accompanying respiratory distress and tachycardia. The patient required ventilation support. Plasma exchange was performed every other day, and total of five times due to the poor general condition. Mycoplasma Ig M was positive. The patients’ respiratory distress and paralysis recovered completely after seven days. Since his facial paralysis had also regressed in 14 days after onset, the patient was out of follow-up. |
pmc-6572536-3 | A 14-year-old female patient was admitted to the children’s neurology department for bilateral peripheral facial paralysis, diplopia, ptosis, dysphagia, and dysarthria with no weaknesses on the limbs (). The prodromal symptoms included upper respiratory tract infection for seven days. The patient had no significant details in her medical, neurological or family history.
Bilateral ptosis and mydriasis, slurred speech, difficulty in swallowing, aphonia, bilateral palatal palsy, tongue movement limitation, and hypoacusia occurred on the second day of hospitalization. Sternocleidomastoid and trapezius muscles strengths were weakened. Bilateral muscle strength of arms were 3/5, and limbs were 4/5, but the patient’s tendon reflexes were well protected. Extensively, she indicated bilateral CN III, IV, VI, VII, VIII, IX, X, XI, and XII involvements, but there were no signs of cerebellar involvement such as ataxia, or any other symptoms indicating sphincter or autonomic dysfunctions. The patient fully co-operated and was conscious with no cognitive impairments. Cranial MRI imaging was normal. The laboratory tests including blood count, thyroid function tests, Venereal Disease Research Laboratory (VDRL) and antinuclear antibody (ANA), C3, C4 were normal. On the tenth day of the illness, CSF was tested, and white blood cell count was normal, but total protein concentration (98 mg/dL) was significantly elevated. Due to the rapid progression, respiratory distress, and hypertension, a daily plasma exchange was planned, and applied a total of five times, every other day. NCS showed reduced CMAP amplitudes in motor conductions with normal nerve conduction after three weeks of illness. Serum antiganglioside antibodies, anti-GQ1b were positive while GM1, GD1b, GT1a, GT1b, GM3, and GM2 were negative. As an etiological agent, human rhinovirus was positive. Patients dysarthria and extraocular palsy begin to regress after seven days. Multiple cranial neuropathies of the patient which include facial paralysis entirely recovered on day 52. A follow-up study after 1.5 years did not indicate any proof of recurrence. |
pmc-6572536-4 | An eight-year-old boy was brought to the emergency department with sudden onset of weakness and respiratory distress. His consciousness was confused. Areflexic acute flaccid paralysis was present on all four extremities. Laboratory tests showed elevated erythrocyte sedimentation rate in small quantities (erythrocyte sedimentation rate; 21 mm/h, average 15 mm/h). Blood count, acetylcholine receptor antibody, thyroid function tests, and other laboratory findings were in normal range. There was no cell in CSF, but CSF protein was high (65 mg/dL). Bilateral peripheral facial paralysis developed on the second day of hospitalization (). NCS showed a decrease of the upper extremity sensory and motor action potential, with increased distal latencies. Bilateral peroneal–tibial nerve combined muscle action potential (CMAP) and sural nerve sensory action potential could not be obtained. Bilateral peripheral facial paralysis developed on the second day of hospitalization (). Plasma exchange was given every other day, and total of three times due to the respiratory distress. He developed resistant hypotension as an autonomic dysfunction and pulmonary infections. Hypotension could not be controlled, and the patient developed cardiac arrest and died on the sixth day of hospitalization. |
pmc-6572615-1 | A 77-year-old man with no history of smoking was admitted to our hospital due to worsening dry cough and dyspnea on exertion over the previous two months. The previous year, he was tentatively diagnosed with asymptomatic idiopathic interstitial pneumonia (IIP) at another hospital. Reticular infiltrates on computed tomography (CT) examination, performed at the time of his initial admission to our hospital, revealed the progression of IPF when compared with CT images obtained one year previously ().
Laboratory findings did not reveal any collagen disorders associated with interstitial pneumonia (IP). These investigations, however, did reveal elevated levels of fibrotic markers KL-6 (1448 U/mL), SP-A (66.4 ng/mL), and SP-D (353 ng/mL). The patient also had a familial history of IPF: his uncle had died from it and his niece had the disease. We diagnosed this case as probable usual interstitial pneumonia pattern with bronchiectasis in the lower lung field via the multidisciplinary-discussion approach, and prescribed a low dose of pirfenidone (600 mg/day) for a month and 1200 mg/day for the following month, after which his symptoms of dry cough and dyspnea during exercising improved. Although the history of cough occurrence/persistence was not investigated by the questionnaire, symptoms of dyspnea improved from 2 to 0, as measured by the modified British Medical Research Council (mMRC) questionnaire []). The reticular shadow in the lower field of his chest radiograph and his pulmonary function, including forced vital capacity (FVC), were improved three and six months later, respectively. Because he experienced appetite loss with pirfenidone at a dose of 1800 mg/day, he has been taking 1200–1400 mg/day with a proton pump inhibitor for approximately two years, and has experienced no marked side effects. Since he began pirfenidone treatment, the reticular shadow on his chest and his FVC appeared to have improved, and his condition has been stable for more than two years (; A). Although levels of fibrotic markers KL-6 and SP-D were temporarily elevated with no symptoms, 14 months after pirfenidone treatment, they normalized under continuous administration of pirfenidone (B). Interestingly, his serum periostin levels were not high at the time of his initial admission to our hospital and, in contrast with the decrease in levels of fibrotic markers, were not affected by pirfenidone treatment (C,D).
Written informed consent was obtained from the patient for publication of this article and accompanying images. This work was supervised by the Ethics Committee of Gunma University Hospital (No. 13-66) approved on 15 April 2014. |
pmc-6572739-1 | A 9-year-old Arabic boy attending middle school experienced OHCA, witnessed by his fellow students, during a physical education lesson. Coincidentally, he had been fitted with a Holter monitor at the time of the event (Fig. ). His medical history comprised a fetal diagnosis of NSML (formerly known as LEOPARD syndrome due to PTPN11 gene mutation) with characteristic features of hypertelorism, low-set ears with prominent pinna bilaterally, downward-slanting palpebral fissures, slight visual disturbances, multiple freckles and lentigines on his face and body, and mild pulmonary stenosis and asymmetric septal hypertrophy diagnosed post-delivery. He was started on regular doses of β-blockers after birth and was receiving bisoprolol 2.5 mg once daily at the time of the event. Cardiac magnetic resonance (CMR) imaging 4 months prior to the event showed a maximum septal wall thickness of 24 mm. No gadolinium-based contrast agent was given, owing to needle phobia. CMR imaging and echocardiography also showed a dilated and tortuous-looking left anterior descending (LAD) coronary artery. A computed tomographic (CT) angiogram 2 months prior to the event showed an unusually large left mainstem and proximal LAD but no anomalous connections or coronary artery aneurysms.0000000000000000
The boy was generally fit and well with no previous history of syncope, but he had occasional palpitations and mild chest pain when playing sports. There was no family history of cardiac disease. Because he was under pediatric cardiology follow-up at our institution, he was seen in our clinic 2 days prior to the event, where, for risk stratification, he underwent exercise testing and was fitted with the Holter monitor. This showed progression from sinus rhythm to VF (Fig. ) at the time of the event.
Immediately following the collapse at 14:20, a teacher and two first aid workers carried out an initial assessment with the patient in the recovery position, during which he was breathing. Five minutes later, responsiveness and breathing deteriorated, and CPR was started. Paramedics arrived approximately 10 min from the moment of collapse and resumed CPR. The paramedics delivered two direct current defibrillator shocks for VF, following which the patient reverted to sinus rhythm with a total downtime of 24 min.
At the time of the event at 14:21, the boy’s heart rate rose to a maximum of 168 beats/min with an increasing number of ectopic beats and soon changed to torsades de pointes and degenerated into VF. Prior Holter recordings were unremarkable with no evidence of non-sustained VT or arrhythmia. The episode of VF lasted for 24 min before the boy was reverted back into sinus rhythm.
He was intubated and transferred to a district general hospital, where he scored 3 on the Glasgow Coma Scale with decorticate posturing. Cranial CT showed cerebral edema. Neuroprotective measures were put in place and upon discussion with our tertiary center. He was commenced on amiodarone and transferred to our specialist pediatric intensive care unit (PICU). Upon arrival, he was sedated, paralyzed, and ventilated on bilevel positive airway pressure. Antiarrhythmic treatment initially included amiodarone (infusion rate 5 μg/kg/min) and bisoprolol. Neuroprotective measures were continued for 72 hr due to bradycardia (40 beats/min) with hypertension indicating raised intracranial pressure. A course of intravenous co-amoxiclav 500/125 mg every 8 hr was started due to left lower lobe chest radiographic changes suspicious of aspiration pneumonia with a maximum C-reactive protein of 60 mg/dl. The patient’s pupils were equal and reactive with no clinical or electrical seizure activity noted. Six days after admission, he was extubated and started mobilizing around his bed within 1 day. He made a full recovery with only minimal neurologic sequelae.
Echocardiography performed upon admission showed preserved biventricular systolic function (ejection fraction 79%) with no obvious regional wall abnormalities and diastolic dysfunction. His troponin I level upon admission to the PICU was 550 ng/L (normal range, < 40 ng/L), which dropped to 53 ng/L after 48 hr (normal range, < 40 ng/L), and his brain natriuretic peptide (BNP) level was 325 ng/L (normal range, < 20 ng/L). Results of his renal and liver function tests were normal. At discharge from PICU, the patient was alert but not fully oriented to time and space, with short-term memory impairment but appropriate interaction. The result of his cranial nerve examination was normal. Tone in all four limbs was good, and his movement was symmetrical, but his power was slightly reduced. He had no clonus. His deep tendon reflexes were elicited, and he had ataxic gait with some slurring of speech. The findings of brain magnetic resonance imaging performed 7 months after the event were normal. Blood tests done 6 months later showed his BNP level was 154 ng/L, and his troponin I level was within the normal range.
Anti-arrhythmic treatment with bisoprolol (3.75 mg once daily) was continued. In addition, ICD implantation was performed for secondary prevention. Neurological follow-up examinations did not detect any neurological deficits. A care plan for school was developed by pediatric cardiomyopathy nurse specialists, including recommendations for limitation of sporting activities.
This 9-year-old boy, although he had some mild deterioration in his reading, remains at the top of the class in his primary school following an OHCA due to VF. In the 6 months following this episode, there were no subsequent ICD discharges, and overall he was able to recover from the VF arrest without any lasting brain damage and was able to return to moderate exercise.
He will need regular lifelong follow-up, both with device specialists and with cardiologists with expertise in cardiomyopathy, currently scheduled every 3 months. He has been advised to receive endocarditis prophylaxis for dental or surgical procedures with regard to his ICD and complex cardiac disease. |
pmc-6572743-1 | On January 16, 2016, a six-year-old male presented with two days of swelling of the right maxillofacial region with fever and two hours of weakness. He was diagnosed with noma and septic shock, and was admitted to the PMICU at Xinhua Hospital of Shanghai Jiao Tong University in Shanghai, China. The patient is of Chinese Han nationality/ethnicity. He had access to a clean water source, no previous related disease, no weight loss, no history of direct contact with poultry and feces, good general nutritional status, was up to date on his immunizations (at the appropriate age according to national regulations), an absence of any known family history of immunodeficiencies, with unknown sanitation in the home and with unknown oral hygiene status.
The right side of the mouth and the maxillofacial area were swollen and tender 36 h before admission. Then, the swollen area gradually expanded to the entire region of the right maxillofacial tissues. Moreover, the local skin color developed to a darkened red, and his temperature was noted to be 39.4 °C. Two hours before admission, the patient lacked energy and developed significant weakness. One day after the onset of symptoms, the patient developed diarrhea, passing seven to eight loose stools per day.
Admission examination revealed the following: a weight of 23.0 kg (71.0% for 6-year-old boy), a height of 123 cm (85.4% for 6-year-old boy), and a BMI of 15.20. The patient was listless (mental status), had a temperature of 37.4 °C, a heart rate of 163 beats/min, a respiratory rate of 24 breaths/min, a blood pressure of 60/40 mmHg, and a SaO2 of 90%. Results of the laboratory examinations are shown in Table .
The swelling of the right cheek and an observation of local tenderness was obvious (3× 4 cm), and the skin temperature was increased without fluctuation. The dark red ecchymosis of the local skin was seen to extend from the right sulcus to the lower forehead (Fig. a). The oral mucosa was intact without ulceration, and there were many firm and non-adhesive enlarged lymph nodes on both sides of the neck. The skin of the extremities was cold, and the capillary refill time exceeded five seconds. Both lungs displayed thick and coarse breath sounds and wet rales.
After admission, the patient was given fluid resuscitation and anti-shock therapy with vasoactive drugs, including norepinephrine (0.05 mg/kg/min, 24-h maintenance), dopamine (5 mg/kg/min, 24-h maintenance); anti-infective treatment with linezolid (10 mg/kg/min, q8) and meropenem (20 mg/kg/min, q6); plasma albumin(10 mg/kg/min), gamma globulin (22.5 g/d); and CRRT (Swedish Campbell PRISMA blood purifier and M60 filter, dialysis method CVVHDF, and blood flow) was carried out. Blood flow was 70 ml/min, the speed of replacement fluid and dialysate was 550 ml/h, and the duration of dialysis was 12 h per day for three consecutive days. After six hours of treatment, the blood pressure of the patient gradually recovered (90/55 mmHg), and the heart rate decreased (130 beats/min). In addition, breathing was stable, and lung function began to improve. Thirty-six hours after admission, the vital signs of the patient stabilized and returned to normal levels, and vasoactive drug therapy was withdrawn.
On the first day, the swelling of the right cheek was obvious, and local skin ecchymoses of the cheeks gradually expanded. Two days after admission, the ecchymoses had dispersed to the entire right cheek and parts of the lower jaw, following which, the skin and subcutaneous tissues appeared black and were hard to the touch (Fig. b). The nurses made records of vital measurements and assessed the wounds on a daily basis. One week after admission, the skin and subcutaneous tissues had completely formed, and took the shape and a black colored clam-shaped shell (10 × 6 cm) attached to the right cheek, and the pain was reported to have disappeared. However, it should be noted that the pain duration could not be determined due to a lack of records as to when the pain began. Since the patient was too young to provide his opinions adequately, doctors obtained the perspectives and consent of the patient’s parents with regard all of these treatments.
Following treatment, the scar crust was surgically removed ten days after admission, and the necrotic tissue under the clam-shaped zone was removed, exposing a large tissue defect of a triangular area in the right cheek and mandibular region (Fig. c). During this period, nursing care was vital. The wound edge was cleaned daily with 0.9% sodium chloride solution and iodophor, and the wound was treated with applications of 10% sodium chloride solution continuously for 24 h. To ensure the wet dressing effect, the bed nurse used a 50 ml syringe with a micro-pump (4 ml/h) to extract 10% sodium chloride solution connected to an extension tube, with one end of the extension tube fixed to the center of the gauze that covered the wound. During treatment, the bed nurse checked the humidity of the wound gauze every hour to ensure no drip. In addition, the wound gauze was replaced every four hours. The bed nurse examined and cleared the necrotic subcutaneous tissue every 48 h, and checked wound healing progress at every shift.
To reduce the restriction of the mouth opening because of fibrous scar contractions, the responsible nurse used a clean 20 ml syringe to replace gags (a device for keeping the patient’s mouth open during a dental or surgical operation) from the third week after admission, and continued physical therapy that kept the mouth opening for two hours, for a frequency of 3–4 times each day (Fig. d). On January 29, 2016, the patient was transferred to a medical department to continue anti-infective management, wound care, nutritional support and other symptomatic treatment options. Further, the defective area of the right cheek and jaw was seen to be gradually reduced (Fig. a), and the fibrous scar tissue had gradually been formed on the right cheek wound.
Five weeks after admission, the child was generally in good condition and the local wound had essentially healed, and showed remarkable recovery (Fig. b). The vital signs of the patient were stable and the patient was discharged on March 8, 2016. At that time, the right maxillofacial region was slightly swollen, and the wound defect was approximately 3 × 1 cm in dimension. The wound gauze was covered without exudation. The patient was discharged with a set therapeutic regimen that comprised the following: multi-vitamin tablets Sig: 0.5 tablets, oral, qd; ubiquinone capsules Sig: 10 mg, oral, q12h; and ursodeoxycholic acid tablets at 50 mg, oral, tid (ubiquinone capsules and ursodeoxycholic acid were used to treat slight liver dysfunction).
Two weeks after discharge, the patient visited the outpatient clinic of our hospital for follow-up, wherein the patient was shown to have recovered well, and it was recommended as standard practice that surgical cheek repair be performed. The exact time will be decided by the plastic rehabilitation surgeon in the plastic rehabilitation specialized hospital. |
pmc-6572748-1 | A 72-year-old Caucasian man, suffering chest pain, visited our emergency department after being diagnosed as having dyspnea. The dyspnea started 3 months ago and deteriorated the week before visiting our emergency department. His dyspnea occurred with moderate exertion without any associated symptoms. His chest pain was atypical with some parietal characteristics. He was a heavy tobacco smoker with no medical history and with no chronic medications prescribed. However, hypertension seemed to have run in his family.
A physical examination revealed severe systolic murmur in the aortic area radiating toward the left parasternal space, becoming fainter at the apex. Blood pressure was symmetric, measuring 155/75 mmHg, pulse rate was 95 beats per minute (bpm). Lungs were clear on auscultation without crackles or abnormal sounds. A chest X-ray showed normal cardiac silhouette and aortic arch, and both lungs were clear and expanded with no infiltrates or pleural effusions. An electrocardiogram showed non-specific changes with T wave inversion on lateral leads and horizontal ST segment depression on V4–6.
He was admitted to the coronary care unit to follow up on the process of examining his body functions. Transthoracic echocardiography (TTE) revealed an oval-like tissue with clean margins attached to the proximal portion of the anterior leaflet of the mitral valve causing LVOT occlusion during systole. The gradient pressure through LVOT measured 55 mmHg, without organic lesion in the aortic cusps. The left ventricle wall motion was normal. Dimensions at systolic and diastolic phases were normal. Pulmonary pressure was 18 mmHg. No other cardiac anomalies were present (Fig. b, c, Additional file : Video S1).
To obtain more detailed information, transesophageal echocardiography (TEE) was performed. This revealed a parachute-like structure (measuring 13 × 14 mm) attached to the proximal portion of the anterior leaflet of the mitral valve causing LVOT obstruction (Fig. a, Additional file : Video S2).
Metoprolol tartrate 50 mg twice daily was prescribed for our patient until the scheduled surgery. During hospitalization, multi-slice computed tomography (MS-CT) scan was performed. It emphasized the presence of the abnormal mass and its dimensions and location (Fig. ).
He underwent coronary catheterization before the surgery. The angiography showed ostial lesion and severe stenosis in the mid left anterior descending (LAD) in addition to 80% stenosis in circumflex (CX), and the right coronary artery (RCA) had multi-sequential lesions beginning from the first segment (Fig. ).
The surgery was delayed for a month due to a huge workload in the surgical department at that time. Since the case was rare and not fully understood by surgeons, it was classified as “cold case” in comparison to other on-list cases. Later on, our patient underwent coronary artery bypass graft (CABG) surgery and the abnormal tissue was surgically removed. The biopsy was sent to the pathology laboratory for further investigation (Fig. ). The pathology report indicated a pure fibrous tissue with non-differentiated cells. Two weeks later, another TEE was done to assess the flow across the LVOT and the pressure gradient (PG) was normal. No residue of the abnormal tissue was seen. A timeline is shown in Table . |
pmc-6572884-1 | A 41-year-old African American male presented to the emergency department with orthopnea, new-onset scrotal swelling, and bilateral lower extremity edema. His medical history was significant for unspecified childhood cardiac murmur, hypertension, and severe congestive heart failure, with reduced ejection fraction of 15% diagnosed 4 years prior to admission.
On initial presentation, the patient was afebrile, normotensive (102/72 mm Hg), with a normal cardiac and respiratory rate. His oxygen saturation was 98% on room air. Physical examination was significant for jugular venous distention approximately 13 cm H2O. Laboratory investigation revealed an elevated creatinine (1.62 mg/dL) above his baseline (1.05 mg/dL) collected 2 months prior, hyperkalemia (5.0 mmol/L), and hypoalbuminemia (2.3 g/dL). Cardiac troponins were negative. Electrocardiogram indicated normal sinus rate and rhythm, while chest radiography was suggestive of increased pulmonary congestion. Presentation was consistent with heart failure exacerbation and cardiorenal syndrome.
Medical management was initiated with intravenous diuretics and follow-up imaging. The patient began 60 mg of intravenous furosemide administered twice daily with a net goal to diurese 1.5 L daily. Following treatment, the patient reported a decrease in scrotal swelling and lower extremity edema. Repeated laboratory testing demonstrated an improvement in creatinine from 1.62 to 1.30 mg/dL.
Cardiology was consulted to obtain a current transthoracic echocardiogram, which revealed a severely dilated left and right ventricle, global hypokinesis with an estimated ejection fraction of 15% to 20%. The patient was noted to have grade 2 diastolic dysfunction as well as prominent left ventricular (LV) trabeculae concerning for LV non-compaction. Additionally, an abnormality concerning for a dilated coronary sinus versus possible aneurysm of the left circumflex artery was identified. An outpouring structure at the inferior left atrium was suspicious of a PLSVC warranting further imaging.
Cardiology recommended transesophageal echocardiography with bubble study as the preferred imaging technique as contrast venography may compromise renal function. Additionally, his treatment plan was to include ICD placement for primary prevention of sudden cardiac death. The following day, the patient underwent subsequent transesophageal echocardiography with bubble study, which confirmed the presence of a PLSVC (, ).
At this time, right heart catheterization was performed indicating severe pulmonary hypertension, a pulmonary capillary wedge pressure of 65 mm Hg, with a decreased cardiac output and index, 2.13 and 1.1, respectively, necessitating cardiac transplant consideration. He was medically managed with a stable hospital course awaiting ICD placement and transplantation assessment.
Our patient required a facility with transplantation experts who may recognize and prepare for irregularities that may occur during procedures. If our patient was deemed to have decreased venous return during bypass or inadequate innominate vein anatomy, he would be at an increased risk for complications. Additionally, a right-sided approach for ICD placement would be preferential. Ultimately, the patient was transferred to a tertiary care center for ICD placement and cardiac transplantation assessment, as our institution does not have the expertise needed to evaluate and treat this condition. |
pmc-6572942-1 | A 15-year-old female patient was admitted to the department of oral & maxillofacial surgery, complaining of gradually increasing swelling on her left side of mandible, started one year ago with severe and unusual pain at the related region. The patient declined to history of any previous toothache and trauma to the affected site. The review of systems was non-contributory. The past medical and dental histories were unremarkable. Upon examination the patient was moderately built and had a normal intellect.
The intraoral examinaton revealed a bony enlargement extending from median mandible to the retromolar region, and inferior border of the mandible to the crestal marginal level. The depth of the left vestibul sulcus was thoroughyl decreased due to hard bony expansion. The extraoral examination revealed hard uniform and large expansile mass in the left side of the mandible. Facial asymmetry was present. Left submandibular lymph nodes were impalpable and insensitive in palpation ().
Conventional radiographs and computerized tomographic scan showed diffuse increase of the lesion of mandible, with loss of normal trabecular pattern leading to classical ground glass pattern (). The CT scans were performed on a multislice spiral CT unit (Somatom Definition Edge; Siemens, Erlangen, Germany). The exposure parameters were tube voltage -120 kV, tube current -270 mA, and slice thickness -1mm. The axial section CT image of mandible showed expansion of the body of the mandible with few lytic areas bilaterally but greater in degree on the left side and expansion of the left ramus. Ground glass appearance of the bone was clearly appreciable. Laboratory investigations revealed slight rise in erythrocyte sedimentation rate (ESR) and mild change in the alkaline phosphotase level which was approximately 566 units.
The position of the mandibular canal was analyzed through the axial CT, which showed that the vertical distance between crestal margin and inferior alveolar nerve at mental foraminal level on the right and left side of the lesion was 19.06 and 23.50 mm respectively. The horizontal distance between alveolar inferior nerve and other cortex of the mandible at lower first molar region on the right and left side was 5.25 and 15.50 mm respectively.
Two separate interventions through incisional biopsy were made for histopathological examinations. The first histopathological specimen revealed increase in mitotic activity, presence of osteoblastic chain surrounding bone trabecules, which lead us to suspect the lesion as being ossifying fibroma. It also lead us to perform second incisional biopsy. A clinical and radiographic diagnosis of FD was confirmed with pathologic examinatons of the specimen examination ().
The crestal and sulcular incision was made extending from posterior edentulous area to the median mandible with vertical releasing incision in anterior mandible. Surgical shaving and recountering of mandible through delicate preservation of the mental nerve in the left side of the mandible was performed. Mucoperiosteal elevation was made with identification of the margin of mental nerve. The expanded bone was removed throughout the lesion excluding the bone surrounding the mental foramina. Then gradual osteotomy was performed by chiesel and mallets according to the anatomy of mantel foramina which was analysed via computerized tomography. Horizontally, 8-9mm of bone surgical shaving was performed symetrically with the reference of right mandibular region. CT displayed a vital role for identification of the mental foramina during osteotomy especially in the bone surrounding mental nerve bundle. The surgical technique included intersecting with oscilating saw, performing osteotomy by chiesels, recontouring with big round burs and rasping with a bone file. Mucosal healing was uneventful. Facial esthetic lines were obtained in the evaluation from the frontal aspect. In evaluation from the lateral profile, bone expansion at inferior border of the left mandible was not eliminated due to staying away from invasive technique (extraoral approach) during pubertal phase.
No paresthesia was seen during the early and late postoperative period. The patient was followed up for 12 months. The patient was satisfied with both aesthetic and functional results ( and ). |
pmc-6572970-1 | Patient 1 (IV-1) was 11 years old girl at the time of examination and blood extraction. She presented with proptosis, delayed speech, developmental delay, dysmorphic features and microcephaly. Head circumference was 48 cm<1 percentile -3.8 SD. She also have tumor in the chest cage. She had no other neurological problem such as progressive cognitive decline, seizures and spasticity. |
pmc-6572970-2 | Patient 2 (IV-2) was also a 9 years old girl. She had dysmorphic features and developmental delay also has speech problem along with microcephaly. She also has delayed in walking (walking started at the age of 4 years) and was unable to express her feeling. The head circumference was (48 cm <1 percentile (-3.2 SD). She had no other neurological finding, such as seizures, spasticity, or progressive cognitive decline. The phenotype were similar to the previously reported patients associated with WDR62 gene for primary microcephaly. |
pmc-6573156-1 | A 44-year-old female went to her primary care physician for a regular visit and subsequently laboratory work obtained post visit revealed a hemoglobin of 5 g/dL. The patient was called immediately and urged to visit the nearest emergency department. The patient endorsed a 2-month history of fatigue and unintentional 60 pounds weight loss. Laboratory results demonstrated AIHA, C3 positivity, elevated immunoglobulin (Ig)G, elevated lactate dehydrogenase (LDH), low haptoglobin, elevated reticulocyte count, elevated RDW-CV (red blood cell distribution width-corpuscular volume), positive direct Coombs test, thrombocytopenia, and proteinuria, all of which led to an underlying ES. The patient was started on high-dose methylprednisolone 500 mg intravenous for 2 days, followed by oral prednisone taper; computed tomography chest/abdomen/pelvis with contrast was obtained for new band-like pain wrapping around the chest, which revealed a compression fracture of the L1 vertebral body. A bone marrow biopsy of the left posterior superior iliac spine was obtained demonstrating plasma cell myeloma making up greater than 80% of the marrow elements in areas with other areas less involved by the plasma cells. Additionally, the bone marrow biopsy revealed absent iron deposits in the marrow as well as normal myeloid, erythroid, and megakaryocytic elements. Flow cytometry was performed demonstrating monoclonal plasma cells, which comprised 20.3% of the total cells (). Plasma cells showed cytoplasmic kappa light chain restriction and showed CD19 neg, CD20 neg, CD38 bri, CD45 dim to neg, CD56 neg, CD138 mod, and cKappa mod (). The serum protein electrophoresis confirmed monoclonal gammopathy with IgG-K. Quantitative IgG at presentation was 7468 with very low IgA and IgM, markedly elevated Kappa free light chain of 1879, and elevated β-2-microglobulin of 6.99. Cytogenetics were normal. As her hospital course continued, her reticulocyte count normalized following multiple blood transfusions, and her pain gradually resolved. She was initiated on bortezomib treatment prior to discharge with close outpatient hematology-oncology follow-up. |
pmc-6579323-1 | A three-year-old male child was admitted to the pediatric ward of Dr. Ruth KM Pfau, Civil Hospital Karachi (CHK) with a one-year history of generalized weakness, loose motions, decreased appetite and intermittent fever not associated with rigors, chills or night sweats, an eight-month history of inability to walk and sit, polydipsia, polyurea, abdominal distention and loss of neck holding for 14 days. He had a previous history of hospitalization six months ago due to the same complaints. The patient was accompanied by his mother. He weighed 6 kg, is the 7th born child to his parents and was delivered at term to a 37-year-old G7P7 mother via normal vaginal delivery. The mother did not report any complications or illnesses during pregnancy. He cried immediately after birth, and there were no complications during or after birth. There is no consanguinity between mother and father. The child was vaccinated but was malnourished, with an unremarkable family history.
The patient also developed diarrhea which was bulky in consistency, green in color with seven episodes per day after every meal intake. Diarrhea was associated with abdominal distention and vomiting. The mother then started giving him a combination of trimethoprim-sulfamethoxazole, after which diarrhea subsided. The child developed neck holding at four years of age, he started sitting at eight months and started walking with support at 12 months of age. The child was first breastfed within three hours of delivery and was exclusively breastfed up to six months. Complimentary feeding was started after six months with pulses, mashed potatoes, porridge and chicken. Breastfeeding was continued up to two years. Currently, the child takes 1-2 feeds per day. The personal history revealed that the patient was sleeping normally, but the appetite was decreased. The mother also noticed a weight loss, altered bowel habits, and micturition was normal.
On examination (O/E), the patient was lying on the bed irritated, severely wasted and emaciated with visible bony deformities. Initial vitals included blood pressure (BP) 110/70 mmHg, a regular pulse of 90 beats/min, a respiratory rate of 20 breaths/min, and a low-grade fever of 100° F. The patient was anemic and dehydrated, while, there was no presence of edema, clubbing, cyanosis, and lymphadenopathy. On further examination, parietal and frontal bossing, rachitic rosary (Figure ), widening of wrists and knock knees (it's a valgus deformity in which legs curve inwards so that the feet are apart when the knees are touching) were found as well. On abdominal examination, it was soft, non-tender, distended with mild tenderness on both flank regions, with a centrally placed umbilicus. The liver was palpable three fingers below the right costal margin. Gut sounds were audible 3-4 sounds/min. All other systems were unremarkable.
The anthropometric measures of the child are as follows: weight = 6.5 kg, occipitofrontal circumference = 49.5 cm, height = 72.5 cm, mid-upper arm circumference = 8 cm, upper segment = 45 cm, lower segment = 27.5 cm, weight for height = 6.5/9 *100 = 72.2 (moderately low) and height for age = 72.5/94.6*100 = 76.6 (severely low).
On investigations performed, complete blood count (CBC) showed a hemoglobin (Hb) of 5.4 gm/dl, mean corpuscular volume (MCV) of 82 fl and a platelet count of 187,000/mL. The total leukocyte count (TLC) was 10.6 x 109/L, including 39% neutrophils and 48% lymphocytes. His inflammatory markers were raised with a C-reactive protein (CRP) of 23 mg/L [Normal (N) = 3] and an elevated erythrocyte sedimentation rate (ESR) of 115 mm/hr (N = 0-22) for men and (N = 0-29) for women. The clotting profile showed an international normalized ratio (INR) of 1.01, while prothrombin time (PT) was 10.6 seconds.
The urea creatinine electrolytes (UCE) were within normal range except decreased potassium levels of 2.8 mEq/L. The levels of calcium, magnesium and phosphate in blood were 15.1, 1.9 and 4 mg/dL, respectively. The blood culture showed a growth of Burkholderia species. The urinalysis showed a pH of 5.0, specific gravity of 1.025, with the presence of protein and blood. Additionally, numerous red cells were seen along with yeast and 4-6 pus cells per high power field (HPF). The urine culture showed growth of Candida species. The stool analysis showed that the stool was hard, acidic, brown in color with 1-2 pus cells per HPF. His vitamin D levels came out to be 54.29 ng/mL, and parathyroid levels were 8.36 pg/ml. Liver function tests showed a total bilirubin of 0.28 mg/dL, direct bilirubin of 0.21 mg/dL and levels of alkaline phosphate alanine aminotransferase were 368 and 3 units per liter, respectively.
The X-rays of the chest (Figure ), skull (Figure ) and femur (Figure ) are attached below. Additionally, ultrasound of kidney ureters and bladder (KUB) showed an incidental finding of bilateral renal calculi (right kidney at lower pole measuring 0.7 cm, in the left kidney at mid pole measuring 0.7 cm), along with bilateral grade 2 renal parenchymal changes. The urinary bladder was normal in thickness with no presence of focal mass, calculus or diverticulum.
Considering the diagnosis of OI, an ophthalmology review was done to look for lens dislocation and blue sclera, but neither was present in both eyes. However, the left eye showed a corneal thinning nasally, temporally and inferiorly.
During the hospital stay, the patient was intravenously given cefotaxime 220 mg, piperacillin-tazobactam 700 mg, and meropenem three times a day. Additionally, linezolid 70 mg was injected every eight hours, along with injections of bisphosphonate 7 mg for three days, amikacin 55 mg twice a day for 14 days and fluconazole 85 mg loading dose, 45 mg once a day for 10 days. The patient was also given a teaspoon of the combination (artemether and lumefantrine) once a day. Three pints of red blood cells were transfused as well, after which his Hb became 10.6 mg/dL. During the stay, the child had a prolonged course of fever with pancytopenia, which improved on injections of meropenem, amikacin, and fluconazole. |
pmc-6579325-1 | This 80-year-old male had a past medical history of colon resection with chemotherapy in 2000 and a stroke in 2005. In 2006, he had L3, L4 and L5 lumbar decompression and instrumentation for lumbar stenosis. He did well until 2009 when he developed low back and bilateral leg pain, more on the right. He had a magnetic resonance imaging (MRI) scan showing adjacent segment disease at L2-L3 with stenosis. He underwent a second lumbar surgery with an extension of the previous L3-L5 instrumentation to L2 with supplemental lateral mass bone fusion. He continued to complain of severe to moderate pain on a continual basis after which he elected to have an epidural neuromodulator placed in 2010. He developed an infection at the battery site and it was removed in 2011. From 2011 to 2018 he has multiple lumbar steroid injections for pain control and was taking opioids daily with only temporary relief. He then underwent a second implantation of a neuromodulator and his leg pain resolved, but shortly after that, he began complaining of upper low back and lower thoracic pain that was constant and different from his previous lumbar fusion pain. The area of pain was localized under fluoroscopy and found to be centered at the T12 and L1 spinal segment above the previous fusion and instrumentation at L2. When computerized tomography (CT) scans from early 2017 were compared to 2018 there were worsening vacuum changes within the T12 fracture as well as in the disc space at T12-L1. When reviewed with neuroradiology, it was felt that the vertical fracture line involving the anterior inferior one-third of T12 extended into the inferior endplate of T12, and connected to the T12-L1 interspace as well (Figure ).
Detailed comparison of each coronal and axial CT reconstruction slice from 2018 clearly demonstrates the marked progression in the osteonecrosis along the T12 anterior fracture clearly connected to the T12-L1 interspace (Figure ).
After detailed review of the different films with the patient, it was felt that stabilizing the fracture and T12-L1 disc space would be appropriate. He did not want to consider any further open instrumentation but agreed to percutaneous placement of cement along the fracture and into the disc space. It was also decided to use CortossR cement (Stryker, Kalamazoo, Michigan, USA) which is both bioactive and has more fluid-like flow characteristics rather than denser polymethylmethacrylate bone cement (PMMA). It was felt this would allow the cement to flow better into the fractures and bone defects.
Technical steps of the procedure
The procedure was divided into four different steps (Figure ). The patient was placed in a prone position with mild sedation and local anesthesia. First, fine 20-gauge spinal needles we placed to mark the pedicles at T12 and L1. Next from the left side, away from the vertical fracture 2 cc of non-ionic contrast were injected with a 22-gauge needle into the T12-L1 disc space to document if it communicated with the vertical fracture. Under fluoroscopy, the contrast could be seen passing form the disc space into the vertical fracture line of T12 establishing the fracture and disc were connected. Second, an 11-gauge vertebroplasty cannula was introduced into the left T12-L1 disc space (Figure ). A fine curette was passed through the cannula to the T12-L1 disc space to further open the communication (Figure ) and then 1.4 cc of Cortoss cement was injected, which slowly flowed from the disc space into the base of the fracture (Figure , ). Third, to guarantee filling of the vertical part of the fracture on the right side, another 11-gauge vertebroplasty cannula was introduced through the pedicle of T12 and advanced under fluoroscopy until the fracture line was encountered (Figure ). The softness and gap of the fracture could be clearly felt and then a bone drill and curette were passed to open the space allowing another 1.4 cc of Cortoss to be injected into the vertical fracture (Figure ). Finally a cannula was introduced into the L1-L2 interspace where there was additional osteonecrotic changes and an additional 1.4 cc of Cortoss cement was injected to L1-L2.
The patient tolerated the procedure without problems and noted a significant decrease in the pain level in the recovery room. The three-month and six-month follow-up has continued to demonstrate resolution of the upper lumbar and lower thoracic pain with resumption of his activities. A follow-up CT scan was performed three months after the procedure to document exactly the position of the bone cement relative to the fracture and the progressive vacuum changes both in the T12-L1 disc space and the vertical avulsion fracture. The follow-up CT scan shows there is scattered cement placement both in the fracture and the T12-L1 disc space but the large vacuum cleft and especially the tract connecting the spaces are filled with cement (Figure ). |
pmc-6579326-1 | A 58-year-old male was evaluated at an outpatient clinic for difficulty in swallowing for the last few months. He complained of dysphagia with solid food but faced no problem with a liquid diet. The patient denied any odynophagia, vomiting, symptoms of gastroesophageal reflux, or weight loss. He did not have any significant past medical history and did not smoke or drink alcohol. Upper esophagogastroduodenoscopy (EGD) was performed for further assessment, which showed, a giant, pedunculated mass arising from the esophageal wall at 18 centimeters (cms) from the incisors, near the cricopharyngeus and extended up to 36 cms from the incisors (Figure ).
The lesion was partially obstructing and not circumferential. The biopsy was negative for malignancy, and it was suspected to be a giant fibrovascular esophageal polyp. The patient was referred to our center for further investigation and management. We performed a computerized tomography (CT) scan of the chest, which showed severe esophageal dilation, measuring up to 5.4 cms at mid-mediastinal level, with retained food debris. After a multidisciplinary discussion between gastroenterology and the thoracic surgery team, a decision was made to endoscopically resect the mass.
During endoscopy, the mid-portion of the lesion was noted to have a large multi-lobulated mass (Figure ).
At this point, a snare was used to attempt to resect the base; however, due to the presence of the mid lesional, multi-lobulated mass, we were unable to get around it; therefore, electrocautery was used in combination with an IT knife (KD-611L, Olympus America, PA, US) to transect the lesion at the base (Figure ).
At the completion of this, there was adequate hemostasis at the base and an endo clinch was used to further reinforce it. The entire mass was attempted to be pulled out of the esophagus but could not be moved out past the upper esophageal sphincter. Therefore, it was pushed back into the stomach, cut into smaller pieces using a hot snare, and removed in a piecemeal fashion (Figure ).
The specimen was sent for routine pathological evaluation. A barium esophagram performed on the first postoperative day showed no evidence of a leak, and the patient tolerated a clear liquid diet without any complications. The pathology report revealed a diagnosis of DDL. The patient was advised about further imaging with positron emission tomography (PET)-CT scan and referral to a radiation oncologist, but he refused additional treatment. |
pmc-6579327-1 | A 60-year-old woman with a past medical history of remote breast cancer and depression was evaluated at an outside hospital emergency department for high fevers, myalgia, fatigue, productive cough, and chills. She had a recent gastrointestinal illness after eating fish and salad at a new restaurant, which spontaneously resolved. Two days afterward, she began experiencing fevers associated with fatigue and drenching sweats that occurred twice daily and were not alleviated with antipyretics. Additionally, she reported headaches, sinus congestion, and a sore throat that resolved with antibiotics prescribed for sinusitis.
Her vital signs were significant for a temperature of 39.4°C. Her physical exam did not disclose temporal tenderness, asymmetrical pulses, conjunctival injection, oral ulcers, cervical lymphadenopathy, or rashes. Her initial laboratory studies were remarkable for a white blood cell count (WBC) of 21,700/uL, C-reactive protein (CRP) of 26 mg/L, and erythrocyte sedimentation rate (ESR) of 74 mm/hr. Computed tomography (CT) of the chest with contrast showed diffuse, abnormal soft tissue around the ascending aorta and aortic arch with fat stranding, which was consistent with aortitis (Figure ). She was transferred to our hospital in Seattle, Washington, for rheumatological management of aortitis.
On repeat laboratory evaluation, WBC was 18,000/uL, ESR was 105 mm/hr, and CRP was 319.7 mg/L. Rheumatoid factor, anti-cyclic citrullinated peptide, antinuclear antibody, anti-double-stranded DNA, antineutrophil cytoplasmic antibody, and serum IgG4 subclasses were unrevealing. Her persistent double-quotidian fevers, elevated inflammatory markers, and aortic findings on CT were concerning for an infectious versus inflammatory aortitis. Potential infectious etiologies of aortitis included tuberculosis (TB), human immunodeficiency virus (HIV), syphilis, and enteric pathogens such as Salmonella. Serologic and fecal testing for these infectious etiologies were negative.
The differential for noninfectious, inflammatory conditions included giant cell arteritis (GCA), Takayasu’s arteritis, anti-neutrophilic cytoplasmic autoantibody (ANCA) vasculitis, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), immunoglobulin G4 (IgG4)-related disease, and Erdheim-Chester disease. Her lack of suggestive clinical history and negative serologies made RA, SLE, and ANCA vasculitis unlikely. Her high fevers and significantly elevated inflammatory markers were less suggestive of IgG4-related disease or Erdheim-Chester disease, and imaging did not demonstrate a suggestive pattern of involvement in other organs. There was also no evidence of malignancy on axial imaging.
The patient was diagnosed with isolated aortitis given her presenting constitutional symptoms, significantly elevated inflammatory markers, and CT chest finding of diffuse fat stranding surrounding the ascending aorta and aortic arch. Her isolated aortitis may be a limited variant of GCA or Takayasu’s arteritis although she did not have the classical symptoms of either []. Ultrasound of the temporal arteries and vessels of the upper extremities did not demonstrate a characteristic “halo sign,” and temporal artery biopsy was deferred given the lack of suggestive clinical features of GCA. The patient was initiated on prednisone therapy at 60 mg daily with a taper over four months. However, due to steroid intolerance, including fatigue and poor sleep, she was started on weekly tocilizumab 162 mg subcutaneous injections within one month of diagnosis. Her elevated inflammatory markers and symptoms resolved quickly and she remains in remission at 10 months of follow-up. Follow-up CT chest demonstrated the attenuation of inflammation around the aorta (Figure ). Even though pseudoaneurysms were noted, these were felt to be likely sequelae of the initial episode. They were stable on further repeat imaging. We plan to continue with tocilizumab for at least 18 months, although the optimal duration of therapy is unclear []. |
pmc-6579330-1 | A 16-year-old Italian boy was admitted with a seven-day history of persistent fever and chills associated with painful swelling of the right shoulder and pharyngitis. He had previously received four days of cefixime and azithromycin treatment. He did not report any recent dental treatment, surgery, or drug abuse. His past cardiac history was unremarkable. The patient was in good general conditions and had normal vital signs (blood pressure: 125/65 mmHg, regular heart rate: 84 beats/minute). He had a temperature of 100.4°F (38°C). Cardiovascular examination revealed a systolic heart murmur 2/6 at the mesocardium. The pharynx was normal and minimal acne was observed on the skin. Blood tests indicated neutrophilic leukocytosis (white blood cell count: 13x 103/µL; neutrophils: 9.7x103/µL) as well as elevated lactate dehydrogenase (266 mU/mL) and C reactive protein (CRP; 18 mg/dL). The urine analysis was negative for infection. The electrocardiography (ECG) demonstrated sinus tachycardia, and the chest x-ray was normal. A bone marrow aspirate was performed to exclude hematological malignancies. Two sets of blood cultures were drawn, and empirical treatment with amoxicillin/clavulanate plus vancomycin was started. Blood cultures were found to be positive for gram-positive cocci in chains, which were later identified as streptococcus group A (Streptococcus pyogenes). The patient was admitted to the Infectious Disease Department and ceftriaxone (2g, twice daily) plus ampicillin (12g/day) were started. The transesophageal echocardiogram (TEE) documented moderate mitral regurgitation and multiple mobile filamentous structures attached to the posterior mitral leaflet (PML) of 1.1 cm in length suggestive of vegetation (Figure -).
The hemodynamic stability of the patient (he had normal values for atrial natriuretic peptide and no signs of heart failure) and the short course of antibiotic treatment were the reasons for not performing urgent surgery on the mitral valve after consultation with cardiac surgeons. Gentamicin (3mg/kg daily) was started instead of ceftriaxone on day seven. His abdominal ultrasonography was negative for liver or splenic embolisms. Painful erythematous nodules (2 to 3mm) were observed on the skin of the right sole, suggestive of secondary lesions. No other skin lesions appeared during the following days, and the neurological examination was steadily normal. The patient underwent weekly ECG evaluations during antibiotic treatment.
A second TEE done on the 12th day of antibiotic therapy found worsening of the endocarditis and growth of the vegetative lesions on the PML. On the 14th day, a cardiac magnetic resonance scan excluded either concomitant rheumatic heart disease or peri-valvular abscess due to Streptococcus pyogenes. At the ECG exams on the 19th and 25th days of hospitalization, the vegetant lesions were not observed (Figure G-I). Gentamicin treatment was continued for two weeks, ampicillin for four weeks, and then the patient was discharged. At the clinical control checkup six months later, the patient was asymptomatic with normal vital signs. A blood test revealed normal white blood cells (WBC) count and CRP levels. Transthoracic echocardiography (TTE) showed a low-grade mitral insufficiency consistent with previous endocarditis of posterior commissure of the mitral valve with normal left ventricular ejection fraction. |
pmc-6579338-1 | A 76-year-old Caucasian male with a history of chronic kidney disease (CKD) stage 3, type 2 diabetes complicated by neuropathy and retinopathy (HbA1c 8.6%), atrial fibrillation on dabigatran, hypertension (HTN), coronary artery disease status post (s/p) three-vessel coronary artery bypass grafting (CABG), heart failure with preserved ejection fraction (HFpEF), peripheral artery disease (PAD) with prior right below knee amputation (BKA) and recent left lower extremity transmetatarsal amputation, and Lisfranc amputation presented due to worsening left foot wound dehiscence. The patient was seen by podiatry prior to initial presentation, where left foot osteomyelitis was suspected given the worsening discharge, odor, and erythema. In consultation with vascular surgery, the left foot was deemed unsalvageable and amputation was recommended.
Initial vitals were significant for temperature 100.3 degrees Fahrenheit (normal range 97.7-99.5 degrees Fahrenheit), pulse 79 (normal range 60-100), blood pressure 138/70 (normal 120/80), respiratory rate 20 (normal range 12-20), with 94% oxygen saturation on room air (normal range 95-100%). On admission, labs were significant for a normal white blood cell (WBC) count of 8.6 K/cmm (normal range 3.6-11.0) with evidence of acute kidney injury (AKI) superimposed on chronic kidney disease (CKD) Stage 3 with a creatinine of 1.7 mg/dL (patient's baseline of 1.1 mg/dL, normal range 0.7-1.5 mg/dL). Radiographic studies of the affected foot revealed air pockets distal to the second and third cuneiforms, felt to represent the extension of deep wounds, raising concerns for chronic osteomyelitis. The patient was started on vancomycin, aztreonam, and metronidazole, given a prior history of piperacillin/tazobactam allergy, and was admitted to medicine for further management. During hospitalization, the patient’s kidney function continued to worsen (Cr: 1.7 mg/dL -> 2.7 -> 3.7 -> 4.4 -> 4.7 -> 5.7 mg/dL) with poor urine output (100-150 cubic centimeters (cc) daily or 0.05-0.07 mL/kg/hr, normal range 800-2000 mL or 1-2 mL/kg/hr). Blood cultures showed 48 hours no growth to date (NGTD) while wound cultures were positive for Staphylococcus aureus with gram-negative rods. Given worsening AKI and positive wound cultures, infectious disease and nephrology were consulted. With concern for medication-induced AKI, the decision was made to switch the patient to monotherapy with intravenous (IV) ertapenem 500 mg daily. However, the patient’s renal function continued to deteriorate, a temporary hemodialysis catheter was placed, and he was initiated on hemodialysis. The differential for the etiology for this patient’s AKI was extensive and included vancomycin-induced nephrotoxicity, obstructive causes (ruled out with no hydronephrosis seen on renal ultrasound and normal bladder scan), vascular causes (no renal artery stenosis or arteriolosclerotic occlusive disease observed on renal artery Doppler ultrasound), autoimmune causes (anti-nuclear antibody (ANA) negative), and vasculitides (antineutrophil cytoplasmic antibody (ANCA) studies negative). The patient required aggressive fluid removal with hemodialysis and ultrafiltration as he remained volume overload and continued to require supplemental oxygen.
Following a five-day clopidogrel washout, a renal biopsy was performed to further workup the etiology of this patient’s anuric AKI. Light microscopy of the kidney biopsy demonstrated diffuse endocapillary proliferative, exudative glomerulonephritis, and increase in mesangial cell counts, consistent with infection-related glomerulonephritis (Figure ). In addition, moderate to severe nodular glomerulosclerosis with prominent hyalinization was present in glomerular capillary loops, consistent with chronic kidney disease secondary to diabetic nephropathy (Figure ). Direct immunofluorescence staining for complement C3 revealed positive glomerular wall and coarsely granular mesangial staining (Figure ). Per the biopsy report, other sites revealed tubular atrophy and interstitial fibrosis (moderate) and arterio/arteriolosclerosis (severe) (not shown). In short, the patient’s renal biopsy results were consistent with acute infection-related glomerulonephritis in the setting of CKD, likely secondary to HTN and diabetes.
Left ankle disarticulation (left guillotine below knee amputation (BKA)) was performed by vascular surgery to treat the patient’s left foot osteomyelitis 28 days after initial admission, after which he completed IV ertapenem for 72 hours at the recommendation of the infectious disease team. Despite an initial reported improvement in urine output to 200 cc daily (0.010 mL/kg/hr, normal range 1-2 mL/kg/hr) following the procedure, the patient remained hemodialysis-dependent on outpatient follow-up, reporting <100 cc urine output per day (0.05 mL/kg/hr, normal range 1-2 mL/kg/hr) per interview in the two weeks following surgery. |
pmc-6579343-1 | A 25-year-old female patient of Indian descent presented with verrucous hyperpigmented neoformations in the right hemibody at the level of the trunk, abdomen, back, genitals, groin, and leg, sparing the face, neck, and mucous membranes (Figures -). The lesions described presented at birth and progressively increased in size and thickness. The patient's personal history was unremarkable, and maternal history was positive for a circumscribed epidermal verrucous nevus in the left forearm. After birth and subsequently during early infancy, routine blood and urine lab tests, neonatal and auditory screening tests, brain tomography scan without contrast and a skull X-ray were performed, all without pathologic findings. Psychomotor development was normal in all stages of life. The lesions remained asymptomatic during early childhood; however, as the lesions grew in size and became pedunculated, erosions and traumatic detachment occurred. At age 15, the patient received treatment with electrofulguration and CO2 laser treatments in a small area of the abdomen, with scarring and an unaesthetic appearance (Figure ). The patient did not receive any more treatments due to the unwanted results and is asymptomatic to date. Physical examination at the time of presentation showed no abnormalities, other than the lesions previously described. |
pmc-6579349-1 | A 23-year-old male presented to our medical center with pain in the right lower back for three years. The pain was initially mild, gradually increased in intensity and aggravated on walking. Fever, anorexia, cough, and weight loss were not present. The patient was a farmer who occasionally went for cattle herding. His medical history was negative for trauma, recent infection, and prior medical conditions. Physical examination revealed a moderately tender swelling at the right lower back. The gait of the patient was antalgic but rest of the motor examination was unremarkable.
Investigations
Laboratory studies were significant for white cell count 19.6×109/L (normal, 4.5-11.0×109/L) and C-reactive protein (CRP) 269 mg/dL (normal, <3.0 mg/L). Plain radiograph of the pelvis revealed osteolytic lesions in the right ilium and ischium, with extensions to the sacroiliac and hip joints (Figure ).
Magnetic resonance imaging (MRI) of the pelvis showed a large heterogeneous signal intensity mass, centered around the right iliac blade, extending to both the iliac and gluteal sides of the bone and was associated with an extensive bony destruction of the right sacroiliac joint and ischium with a cystic component in the right iliopsoas muscle (Figure ).
T-SPOT®.TB test came out negative. A whole-body bone scan showed increased uptake in the right iliac bone as well as the right sacroiliac and hip joints. Subsequently, an uneventful fine-needle aspiration biopsy was obtained from the right iliac bone. The histopathologic examination of the biopsy specimen showed the cyst wall comprised of a laminated layer and an outer layer of dense fibrovascular tissue. The fragmented tissue had laminated walls, with acute-on-chronic inflammatory infiltrates having an exuberant giant-cell reaction (Figure ).
Differential diagnosis
On the basis of the investigative findings, tuberculosis, osteomyelitis, malignancy, aneurysm, and metastatic lesions were excluded. A diagnosis of hydatid cyst with giant cell reaction of the pelvic bone was established. A full-body evaluation was negative for liver lesions and there was no evidence of concurrent multiorgan involvement.
Treatment
The patient was initiated on oral albendazole 400 mg twice daily. After three months, repeat pelvic radiograph demonstrated a relative regression of the disease (Figure ).
Repeat whole-body bone scan showed relatively reduced uptake of radionucleotide in the right sacroiliac and hip joints and iliac bone, consistent with a slow decrease in the size of the hydatid cyst. The disease relatively regressed on the radiological scans but the clinical symptoms of the patient worsened. Thereafter, surgical intervention was undertaken. The procedure revealed a 5.5-cm cystic area in the ileum with an extension into the ischium, sacroiliac joint, and adjacent soft tissues. The hydatid cyst was carefully aspirated and the cyst wall was excised along with the curettage of the involved area. Adjacent soft tissues and sacroiliac joint were extensively debrided and the area was washed with 20% NaCl solution. A sponge soaked in hypertonic saline was placed for three minutes. The bone gap was filled with bone cement and all layers were closed in reverse order after placing a drain (Figure ).
Particular care was taken to avoid spillage of the cystic fluid. The gross morphology of the cystic lesion resembled a multilobulated ovoid mass. Similarly, extensions of the cyst were also grossly examined and sent for histopathologic examination (Figure ).
The results of the histological analysis of the resected specimen validated the prior biopsy findings.
Outcome and follow-up
The post-procedure recovery was uneventful and he was discharged from the hospital in a stable condition. At the one-month follow-up visit, pelvic radiograph showed bone cement in place, with no sign of recurrence of the disease (Figure ).
The patient is now on oral albendazole therapy with a cycle of one month with two weeks gap and his liver functions are periodically monitored. He continues to do well and is advised for a regular monthly follow-up in the outpatient department. |
pmc-6579356-1 | A five-year-old male child presented to us in a tertiary-care, public hospital setting with fever, pallor, and rash over his body for five days. In addition, he suffered from two episodes of non-projectile, blood-stained vomitus and had developed a non-progressive, black lesion over his nose within the same period. As reported by the mother, his fever spiked around two months ago, was high grade, continuous, not associated with chills, and documented as going up to 103-104°F with an associated acute-onset earache and ear discharge. Four days after the onset of fever - swelling, pain, and limitation of movement were noted at the left ankle joint. The fever temporarily subsided by some medication prescribed at a local clinic and the joint pain was persistent, but the child was not further investigated at this point. Due to a lack of improvement of the symptoms, the mother had brought the child to the emergency room (ER) via which he was admitted to our pediatric ward and administered intravenous antibiotics over the course of the next two weeks, resulting in an improvement of symptoms (joint pain and fever). Following this, the relevant investigations were ordered and in view of the child’s symptoms not being completely alleviated by the antibiotics and his prolonged history, the case was discussed with a pediatric rheumatologist. The labs reported slightly elevated platelet count (451,000/ microliter), raised C reactive protein (CRP - 22.7mg/L), raised erythrocyte sedimentation rate (ESR - 42 mm/hr), and a negative antinuclear antibody test (ANA). The child was diagnosed as a case of oligoarticular juvenile idiopathic arthritis (JIA); treatment was started shortly after diagnosis and the patient was started on sulfasalazine (30 mg/kg/day, in two divided doses) and naproxen (15 mg/kg/day, in two divided doses). The parents were asked to seek an ophthalmologist’s opinion for his uveitis and advised regular follow-up.
After three weeks of treatment, the patient was brought back to the ER with the aforementioned complaints i.e. fever, pallor, rash, vomiting, and a black lesion on the nose for the past five days. On systematic review, the parents reported exertional dyspnea for the past five days. A system-wise conducted clinical examination revealed an increased heart rate (140 bpm), weak peripheral pulses, shifted apex beat with a notable gallop rhythm, bilateral basal crepts, palpable liver of 4 cm, multiple petechiae mainly over limbs and face, and a black colored ulcer at the tip of the nose, with pus discharge at the floor of the ulcer. Musculoskeletal and joint examination were unremarkable.
Based on the history and examination, the differential diagnoses included: JIA with macrophage activation syndrome (MAS), viral fever (dengue) and complicated malaria. Various investigations were carried out to reach a definitive diagnosis, including complete blood count, which showed low hemoglobin (6.3 g/dl), low MCV (71.4 fl), low platelets (2000/microliter), and severe neutropenia (180 cells/mm3). The malarial parasite was not seen and the dengue antigen was also negative. The urea, creatinine, and electrolytes came out normal. The other labs carried out revealed elevated CRP (223 mg/L) and ESR (42 mm/hr). In view of the suspicion for MAS; the liver function tests, fibrinogen, triglyceride, albumin, ferritin, and sodium levels were also checked, all of which were within their normal ranges. Sulfasalazine was stopped at this point due to the child’s extreme ill health.
Initially, the child was managed in the emergency department by administering oxygen, antibiotics (ceftazidime and amikacin), and paracetamol. He was later shifted to the pediatric intensive care unit (ICU) where methylprednisolone was started and platelets and packed RBCs were transfused. Further tests were performed, including blood peripheral smear preparation, which showed pancytopenia, and chest X-ray, which showed bilateral infiltrates.
The child was later shifted to the ward while there were still multiple spikes of high-grade fever. Pus was taken from the nose lesion and sent for culture. The differentials at this point included bacterial sepsis with immunosuppression and infective endocarditis. The culture returned positive for Pseudomonas aeruginosa and antibiotic therapy was accordingly changed to piperacillin/tazobactam, along with colomycin. With the change of antibiotic, the fever and lesion on the nose subsided. The child’s pediatric rheumatologist was consulted again regarding the case and sulfasalazine was restarted when he was stabilized, due to the strong suspicion of JIA. Upon resuming the drug, he first developed an allergic reaction on the same day, which was controlled with steroids and H1, H2 blockers, and he subsequently developed anemia and skin bleeding manifestations (and a generalized erythematous rash) on the successive days. The laboratory investigations run at this point portrayed pancytopenia (reticulocyte count 0.5%). At this time, it was strongly suspected that these manifestations were side effects of the prescribed sulfasalazine, so the drug was stopped and the patient managed conservatively. The child’s condition improved significantly with supportive management, after which he was discharged with instructions to follow-up at the outpatient department with a complete blood count (CBC) that remained within normal limits upon the two occasions it was reported at. Thereafter, the patient was advised regular follow-up.
In summary, the diagnosis was strongly believed to be that of sulfasalazine-induced bone marrow suppression, in view of how the patient had two episodes of pancytopenia (the first having been attributed falsely to MAS) and how his symptoms subsided shortly after stopping the drug. |
pmc-6579360-1 | A 27-year-old male presented to the outpatient clinic with two weeks of lightheadedness without syncope, occasional shortness of breath, and four episodes of palpitations per day that had progressed to chest pain which worsened in an upright position. He also experienced fatigue, hot flashes, and occasional nausea for the past month following a URI. Past medical history was significant for pulmonary nodules found to be stable on serial computerized tomography scans. He denied tobacco or alcohol use, but admitted to marijuana use that ceased when the nodules were discovered. He was thin, but athletic, with a body-mass index of 19. He had clear lungs bilaterally, a blood pressure of 115/74 mmHg, a pulse of 70 beats per minute (bpm), and a regular rate and rhythm without rubs or murmurs upon auscultation. An ECG revealed extensive ST-segment elevations suggestive of pericarditis, which was noted by the ECG machine (Figure ). Review of his medical records revealed an ECG from an ED visit one year prior showing only ER morphology (Figure ).
The ECG tracing shown in Figure exhibited sinus rhythm at a rate of 74 bpm. ST elevations were present in leads II, III, and aVF, with slightly more pronounced elevations in precordial leads V3 through V5. J-point notching was also evident in the inferior leads. Minimal PR depression was seen in the inferior leads. The ST-segment elevation to T-wave height ratio was less than 0.25 in leads V4 through V6.
Based on his symptoms, history of a recent URI, and the presence of diffuse ST elevations on ECG, the patient was diagnosed with AP. He was prescribed NSAIDs and referred to cardiology for follow-up. The following day he went to the ED for continued chest pain. In the ED, an ECG was done and showed evidence of ER changes (i.e. ST elevations and J-point notching), but was otherwise unremarkable. A chest X-ray revealed no acute changes and, a C-reactive protein level was within normal limits. On follow-up, cardiology diagnosed him with AP. A 24-hour Holter monitoring and an ECG were performed, showing no effusion or other abnormalities. After discussing the risks and benefits of treatment, the patient was started on colchicine. His symptoms ultimately resolved within a few weeks. |
pmc-6579521-1 | The patient was a 55-year-old male entrepreneur, who had been experiencing pain of moderate intensity in the mid third of his left thigh for approximately 6 days. He sought emergency care at a hospital in response to a sudden increase in the intensity of the pain combined with swelling at the site of pain. He had a history of smoking equating to approximately 37 pack years. He did not have any other comorbidities. On physical examination he was slightly pale, with tachycardia (120 bpm) and blood pressure at 100 x 70 mmHg. Physical examination by segments was unremarkable for the head and neck, thorax, and abdomen. Vascular examination of the right lower limb found normal auscultation and visual inspection results, with all pulses present and normal. The left lower limb was well-perfused, but there was ecchymosis and a pulsatile swelling between the mid and distal thirds of the thigh, in the anteromedial region ( a). Inspection of the left foot also revealed signs of distal microembolization ( b) and popliteal and distal pulses were absent.
Ultrasonography of the left thigh showed an aneurysmal dilatation of the SFA measuring 5.8 x 5.3 cm and with associated mural thrombi and perivascular accumulations compatible with a ruptured aneurysm ( ). Since angiotomography was not available at the service providing care, the decision was taken to perform emergency surgical treatment.
During the procedure, extensive hematoma was observed involving subcutaneous and muscle tissues in the anteromedial region of the thigh. Once this had been removed, the ruptured SFA aneurysm could be seen ( 3b). There were no obvious signs of active infection. Proximal and distal ligatures were performed and then the aneurysm was resected and samples collected for anatomopathological and microbiological analyses. Revascularization of the limb was then accomplished by interposition of the contralateral great saphenous vein in reverse, with end-to-side anastomosis – taking into consideration the diameter of the femoral artery and the significant destruction of its walls, as illustrated in c. The contralateral saphenous vein was used both because of the probability of associated damage to deep veins in the limb involved in rupture and because of the greater likelihood of injury during dissection, due to anatomic distortions. There were no intercurrent conditions during the procedure
The patient was prescribed prolonged, wide-spectrum antibiotic therapy until the results of the microbiological culture of the aneurysmal fragment were available, showing no evidence of growth of microorganisms. The anatomopathological analysis found true aneurysmal walls, with no specific abnormalities. Supplementary imaging exams did not identify any additional aneurysms or any evidence of valve vegetations suggestive of endocarditis.
At 1-month follow-up, the patient had palpable distal pulses and was free from pain or other problems. |
pmc-6579522-1 | The patient was a 64-year-old female who sought care for a cervical nodule. Color Doppler ultrasonography revealed a large nodule posterior to the left carotid bifurcation and ligature of the right common carotid artery that had been performed during a previous surgical procedure. The patient was nevertheless asymptomatic neurologically. Arteriography ( A) identified a hypervascularized glomus tumor with a maximum diameter of 5 cm, located posterior to the left carotid bifurcation and primarily fed by the ascending pharyngeal artery, in addition to occlusion of the right carotid artery ( 11D). Furthermore, a 4 mm saccular aneurysm was observed involving the left ophthalmic artery. The patient reported having had dermatological surgery previously in the right cervical area, which had involved complications causing her to be admitted to intensive care. However, she had no report or history providing details of that event. Having diagnosed the glomus tumor and contralateral carotid occlusion on the basis of imaging findings, the decision was taken to perform resection of the tumor after preoperative embolization.
Embolization was conducted by infusion of the Onyx® copolymer embolic agent (Covidien, Irvine, CA, USA) 2 days before surgery, via superselective catheterization of the artery feeding the tumor, located at the carotid bifurcation.
The “pressure cooker” technique (
) was employed via a femoral artery puncture, with selective catheterization of the left common carotid artery ( A). Next, a 1.3-F Marathon® microcatheter (Covidien, Irvine, CA, USA) was positioned in the ascending pharyngeal artery, occluding the proximal region. A 1.5-F Apollo ® microcatheter (Covidien, Irvine, CA, USA) was then positioned distal of the Marathon® catheter. The Apollo® microcatheter has a mechanically detachable distal tip. It was used to inject Onyx® until arterial reflux was identified on fluoroscopy ( B). Next, Gluebran® was injected via the 1.3-F microcatheter to secure the tip of the Apollo® microcatheter and achieve arterial occlusion to prevent reflux into the carotid artery. Once the ascending pharyngeal artery had been obstructed, infusion of copolymer was resumed via the Marathon® catheter, to progress in the anterograde direction and fill the hypervascularized lesion ( 33C). Since the hypervascularized tumor had not been completely filled ( C) by endovascular embolization, the unfilled part of the glomus tumor was directly punctured, percutaneously with a 22G needle, guided by the roadmap and fluoroscopy, and percutaneous polymer embolization was used to fill the remaining space (
, D).
Three days after embolization, surgical excision was performed through the longitudinal cervical incision typical of carotid endarterectomy, exposing an enlarged ganglion with a great deal of adherent tissues and signs of inflammation. After identification and isolation of arteries and nerves, a tumor with approximate dimensions of 3 cm x 2 cm was dissected without major bleeding or arterial damage, the dissection planes were identified, and rigorous hemostasis was achieved by ligation of the tumoral vessels and the ascending pharyngeal artery ( ). After excision, a soft silicone vacuum drain was attached and the dissection planes were drawn together. The results of pathology and immunohistochemical assays provided evidence of a paraganglioma with follicular lymphoid hyperplasia and reaction pattern.
Initially, during the immediate postoperative period, systemic pressure was difficult to control, with hypertensive peaks, and intensive monitoring was needed for 5 days. After this period, the patient began to recover gradually, with a reduced need for antihypertensives, and was discharged 7 days after the surgical procedure. The late postoperative period went well, with no neurological events, good wound healing, no stenosis or expansive lesions, and no swellings. Imaging exams conducted as part of a reevaluation 3 years after the procedure did not show any sign of relapse whatsoever ( ). |
pmc-6579525-1 | A 67-year old male patient presented to the otolaryngology clinic with a swelling on the left side of his jaw which had been present for 12 years but had enlarged recently. His medical history included an operation for a swelling on the right side of his jaw at another centre, 17 years previously. However, there was no medical record of that operation. His recent medical treatment included doxazosin for hypertension and inhaler bronchodilator for chronic obstructive pulmonary disease. Pathology examination of the biopsy materials of the swelling excluded malignancy and the patient was scheduled for a parotidectomy operation with a diagnosis of benign Whartin tumor. He was a smoker for 55 years and an ex-coal mine worker and rhonchi were present in his physical examination. Therefore, chest radiography and magnetic resonance imaging (MRI) were performed. In these examinations, a 40 mm ARSA aneurysm was observed posterior of the trachea ( ). Thorax CT angiography with contrast was then performed to determine the relation of the aneurysm to adjacent organs ( ).
Although an endovascular intervention had been planned initially, because of the patient’s comorbidities, the anatomical measurements of the ARSA were inappropriate for placement of an endovascular stent so we decided to perform open surgery. We planned surgical resection of the Kommerell diverticulum through left thoracotomy and repair of the descending aorta with primary sutures or patching of the descending aorta with polytetrafluoroethylene (PTFE) graft. We were also going to implant the left subclavian artery into the left common carotid artery with fine running polypropylene sutures.
Written informed consent was obtained from the patient and he was operated under general anesthesia. The chest cavity was accessed through the 4th intercostal space after left lateral thoracotomy. Sudden abundant bleeding from the posterior wall of the aneurysm occurred during surgical exploration of the aortic arch. The patient was lost because of the massive bleeding and hemodynamic instability. |
pmc-6579726-1 | The patient's clinical history started when she was 13 years old and presented with a generalized tonic–clonic seizure, which lead to a magnetic resonance imaging (MRI) of the brain with the subsequent diagnosis of multiple intracerebral CVs: a left frontal intraparenchymal one (35 mm in diameter) and a left posterior temporal one, both within the parenchyma (23 mm in diameter), and an intraventricular one (30 mm in diameter). Despite the best medical treatment, the epilepsy was not well controlled and the patient had up to three to four epileptic attacks per week. This case was discussed several times at our multidisciplinary meeting, as well as with the patients and the parents. The final decision was to remove the largest and the apparently symptomatic CV, and this decision was guided by a video-EEG (electroencephalogram). The left frontal CV was removed at the age of 14 years, with epilepsy symptoms being temporarily improved. Unfortunately, after 10 months, she started to complain of epilepsy again, with a clinical absence type behavior, pointed for temporal lobe origin type of seizures. Thus, a few months later, the left posterior temporal lesion was removed as well. The second operation gave very good medical results in terms of seizures control. The episodes dropped to one or two focal seizures per year. The third lesion, the intraventricular one, was followed up with a yearly MRI scan. At the age of 21, because the lesion had increased in size (∼8 mm) and because of the patient's desire, we decide to remove it using a transcranial interhemispheric approach. The operation was uncomplicated, and the patient was discharged home a week after the procedure. At that stage, no other lesions were present, and in the following 10 years, the follow-up MRI scans did not show any recurrence or new CVs. When she was 32 years old, on the yearly follow-up scan, a newly developed lesion was identified. This lesion, suspicious for CV, was small (6 mm) and located within the septum pellucidum. Because of its small size, the location, and the absence of symptoms, a conservative treatment option was followed. Unfortunately, the lesion doubled in size in the following 18 months and therefore the patient was very adamant about having it removed (
). We were a bit reluctant because the patient was completely asymptomatic and had not had any epileptic attack for 10 years. Upon neurologic examination, she presented no issues. Finally, we took the decision to remove the lesion and we started to discuss how to approach it. We were wondering whether to use the same interhemispheric approach with the possibility of encountering scar tissue or if it was better to use a new surgical route such as a transcortical one. Finally, we decided to use something completely different and we opted for a transcortical endoscopic approach.
With the patient in the supine position through a single burr hole, placed slightly more laterally in relation to Kocher point, a purely endoscopic approach was performed and the lesion was completely removed (
). A rigid endoscope was used and guided by the neuronavigation. Upon inspection, the lesion (
) presented with two veins attached to it (one rostral and the other caudal). The removal began with the coagulation and dissection of the septum pellucidum superior to the CV location. After accurate coagulation and section of the caudal vein, using endoscopic forceps allowed the creation of a “pedunculated” CV. The insertion of an endoscopic rongeur in the space between the peel-away cannula and the endoscope allowed keeping the CV in place, avoiding its fluctuation in the ventricles. This maneuver allowed the exposition and easy dissection of the rostral vein, which, eventually, was coagulated and cut. The CV was then freed from the surrounding tissue and finally removed. An external ventricular drainage was precautionary left in the right ventricle just for 24 hours.
The histological examination revealed multiple dilated and congested vascular spaces lined by the endothelium, confirming the diagnosis of a CV.
The postoperative course was uneventful, and the patient was discharged home 2 days later. Serial follow-up MRI scans did not show any new or recurrent lesion at 5 years follow-up. |
pmc-6579728-1 | Our patient is a 7-month-old previously healthy boy, who was referred to our tertiary center with an incidental finding of a pelvic mass on ultrasound (US) that was performed as part of the investigative pathway for the febrile urosepsis he was being managed for.
Clinical examination and laboratory work-up were essentially unremarkable. US showed a well-circumscribed, solid, polypoid mass arising from the UB fundus, measuring 2 cm in diameter, with hypervascularity on color Doppler (
). Magnetic resonance imaging (MRI) showed a (20 × 18 × 17 mm) well-defined, homogenous, solid mass arising from the middle/left side of the dome of UB (
). A cystoscopic biopsy was attempted but proved to be difficult as the mass was completely submucosal and not clearly visible.
We proceeded to excisional biopsy through an extended suprapubic incision. The dome of the UB was opened, and the tumor felt elastic, firm, and homogenous (
). The mass was excised completely with grossly negative margins, and the recovery period was uneventful. Histopathology was consistent with a completely excised, poorly differentiated NBL with low mitosis–karyorrhexis index and favorable histology, as per Shimada's classification. Multiplex ligation dependent probe amplification analysis showed no evidence of proto-oncogene N-myc (MYCN) amplification or any segmental chromosomal abnormalities.
Further assessment was made for metastatic disease, including bone scan, bone marrow biopsy, and MIBG (metaiodobenzylguanidine) scan, which were all negative. Urine creatinine, HMMA (4-hydroxy-3-methoxy mandelic acid)/creatinine, and homovanillic acid (HVA)/creatinine ratios were all within normal limits.
Due to favorable prognostic factors, our patient was classified as a very low risk group according to the International Neuroblastoma Risk Group staging system (INRGSS) and was treated by surgical excision only. Annual follow-up with clinical examination and two MRI scans performed after 1 and 3 years postoperatively revealed no evidence of recurrence or residual tumor. The patient remained asymptomatic throughout and was discharged from follow-up after 5 years. |
pmc-6579729-1 | A 7-year-old male child was presented to the Pediatric Department in Shatbi University Hospital with recurrent chest infections since 1 year. Repeated chest X-ray showed left pleural effusion. The child was managed conservatively and discharged from the pediatric department. During the course of follow-up for the respiratory condition an abdominal ultrasound was ordered to investigate a new onset minor abdominal discomfort. An abdominal cyst was found which, otherwise, was not clinically palpable during abdominal examination. Subsequent computed tomography (CT) scanning of the abdomen and pelvis with intravenous contrast revealed a retroperitoneal thick-walled fluid filled mass, measuring approximately 11.5 × 13 cm in close relation to the main pancreatic duct with inflammation of the adjacent pancreatic tissue. Provisional reports indicated a pseudo-pancreatic cyst with further extension into the posterior mediastinum through one of the diaphragmatic hiatus (
). Serum amylase and lipase were markedly elevated (amylase: 45,630 U/I and lipase: 180,000 U/I).
The decision after surgical consultation was to perform laparotomy. The child was prepared for the operation. Through an upper midline incision, the abdomen was explored. This revealed a large, smooth, and fluctuant mass behind the stomach extending up to the posterior mediastinum through the esophageal hiatus, mostly arising from the pancreas. Aspiration of the coffee ground contents was done followed by a drainage procedure by anastomosing the posterior wall of the stomach to the anterior wall of the cyst wall (cystogastrostomy) using running 4/0 vicryl sutures. A Penrose drain was inserted in the left upper quadrant followed by a layered closure. The postoperative course was uneventful. Nasogastric suction and intravenous fluids were continued for 5 days, after which oral feedings were gradually given. The drain was removed after 5 days and the child was discharged from the hospital on the 9th postoperative day. Follow-up abdominal ultrasound was done after 2 weeks and revealed dramatic improvement regarding the size of the cyst. Serum amylase gradually fell to the normal limits. A repeat ultrasound confirmed complete resolution of the cyst after 6 months. The patient is doing well after 1 year of regular follow-up visits. |
pmc-6579797-1 | A previously healthy, 77-year-old female was referred to our hospital, with a lung adenocarcinoma measuring 28 mm in the right upper lobe. We therefore planned a UVATS to resect the tumor. The patient was placed in the left lateral decubitus position under general anesthesia. Then, we made a 4-cm skin incision for the main port in the sixth intercostal space at the anterior axillary line. A wound retractor (Alexis-xs; Applied Medical, Rancho Santa Margarita, CA) allowed the insertion of a flexible thoracoscope (10 mm in diameter, Olympus Optical Tokyo, Japan), endoscopic autosuturing device (GIA Universal; Covidien, Mansfield, MA or Echelon; Ethicon, Cincinnati, OH), and vessel-sealing device (Ligasure; Covidien) via the main port incision. It also allowed specimen extraction.
During operation, we found the incomplete interlobar fissure between the upper and the middle lobe and the abnormal lobulation of the upper lobe. (Fig. ). Therefore, we carried out the so-called modified marionette technique as follows. First, the Internal organ retractor (IOR; Aesculap, Tuttlingen, Germany) applied with a looped 1-0 nylon thread was inserted into the thoracic cavity by the clip applier (Aesculap). The clip applier also allowed the IOR to grasp the targeted lung parenchyma properly. Second, two sets of looped 1-0 nylon-threaded 18-gauge injection needles were prepared (Fig. a). These needles were optimally pierced through the thoracic wall separately (Fig. a and b). Third, the both ends of the 1-0 nylon thread attached to IOR were separately pulled out through the looped nylon extruded from the 18-gauge injection needles. Each thread was clamped by mosquito forceps (Fig. b). The looped nylon extruded from 18-gauge injection needles worked as a pivot, so that the vector of retraction of the IOR was converted into an ideal direction (Fig. ). This method gave the sufficient thoracoscopic views to perform surgery with safe and ease. The patient had an uneventful postoperative course and was discharged in 1 week after the operation without any wound complications. |
pmc-6579800-1 | A 41-year-old man suffering from the bilateral knee and ankle arthralgia for several months was transported emergently to our hospital owing to acute respiratory distress and hemoptysis. Upon arrival, he was in a shock state. Chest roentgenography revealed severe pulmonary congestion; cardiac echogram revealed a large mass in the LA that incarcerated into the mitral valve. Additionally, chest computed tomography (CT) revealed a tumor in the LA; thus, he was diagnosed with acute left heart failure caused by the mass that obstructed cardiac blood flow (Fig. ).
An emergency surgery was performed under cardiac arrest with extracorporeal circulation, which was established in the usual manner with bicaval direct cannulation. Because of the dimensions of the tumor and its pedicle attachment, we could approach through both the wall incisions on the right-side LA from the right upper pulmonary vein and atrioseptostomy from the right atrium. The tumor pedicle widely and irregularly originated from the right upper and posterior LA wall and extended to the lateral LA wall, which included the right upper pulmonary vein. The tumor was visibly extirpated and invaded the LA wall (Fig. ). The shape and function of the mitral valve were intact, and the large defect in the LA wall was reconstructed using a bovine pericardial patch. It was 159 min under extracorporeal circulation, and the aortic cross-clamping time was 123 min.
Extracorporeal circulation weaning and post-operative course were uneventful, and arthralgia in both lower limbs disappeared immediately after surgery. The pathological diagnosis was UPS with clear resection margins (R0 resection), which invaded the atrial muscular layer (Fig. ). Subsequently, as imaging studies soon and 3 months after surgery did not reveal tumor presence, we decided to adopt a more suitable treatment strategy without involving adjuvant therapy after surgery if UPS relapse or metastasis occurred. Specifically, we planned to perform re-surgical resection or proton radiotherapy for recurred or metastatic tumors. In addition, we planned to initiate systemic chemotherapy using a target organ drug or other anti-malignant tumor agents for distant metastasis depending on the local and general conditions of the patient. He was discharged 20 days after surgery without additional treatment and was able to work 2 months after discharge.
However, local recurrence in the LA was observed on positron emission CT (PET) and other imaging studies 7 months after surgery (Fig. a). A tumor was detected on the posterior LA wall adjacent to the incision line of previous surgery. He again experienced arthralgia in both lower limbs. Thus, we selected radiotherapy with proton beam as treatment, and a dose of 75 Gy was delivered to the recurrent tumor in 30 fractions for 45 days. No tumor was observed in the LA on imaging performed 2 months after radiotherapy as an outpatient (Fig. b).
After 6 months, the second local recurrence at a different site in the LA and distant metastasis to the left adrenal gland were simultaneously observed on the results of several imaging tests. In the left adrenal gland, a large solid tumor with an irregular surface and abundant blood flow was observed on enhanced CT scan (Fig. a), and remarkable fluorodeoxyglucose (FDG) uptake was found on positron emission tomography/CT scan (Fig. b). Proton beam radiation for both tumors was selected to conserve the left kidney function. A dose of 60 Gy was delivered to the tumor in 30 fractions in the LA and 46 Gy in 23 fractions in the left adrenal gland. Moreover, chemotherapy with pazopanib hydrochloride (800 mg/day), a tyrosine-kinase inhibitor (molecularly targeted drug), was used in combination radiotherapy. At the end of the second radiotherapy, a larger but cystic and non-enhanced mass in the left adrenal gland was observed on CT (Fig. c). While the patient was receiving chemotherapy for 8 months after the completion of the second radiotherapy, the size of the left adrenal mass apparently reduced. Moreover, neither blood flow nor fluorodeoxyglucose (FDG) uptake of lesions in both the LA and left adrenal gland were revealed on positron emission CT scan (Fig. d, e).
Twenty-seven months after surgery, no active tumor was noted on any imaging result, and he returned to work without symptoms, including arthralgia of the lower limbs. |
pmc-6579888-1 | A 54-year-old female with grade 3 obesity body mass index (BMI 45.2 kg/m2) and type II diabetes (hemoglobin A1c 8.1%) presented to her primary care physician in May 2017 with a chief complaint of left lower extremity edema. Venous duplex revealed no deep venous thrombosis and an X-Ray revealed lower extremity atherosclerosis with no fracture. She was sent to a cardiologist. Electrocardiogram demonstrated normal sinus rhythm and a left bundle branch block. Echocardiography revealed a left ventricular ejection fraction of 25% without significant valvular pathology; heart failure was diagnosed. Renal, liver, and thyroid function, as well as ferritin and potassium levels were within normal limits. HIV was non-reactive. She was not anemic. She was started on a beta-blocker, an ACE inhibitor, and a statin. Cardiac MRI in June 2017, revealed a dilated cardiomyopathy and an ejection fraction of 21%. Coronary CT angiogram revealed an Agatston coronary artery calcium score of 458. Extensive calcification on the CT angiogram precluded assessment of coronary artery stenosis. Hence cardiac catheterization was performed and revealed a cardiomyopathy out of proportion to coronary artery disease with a 30% proximal left anterior descending artery stenosis, a 25% proximal and a 60% distal left circumflex artery stenosis, and a 65% first obtuse marginal artery lesion. The left main and right coronary arteries were without stenosis. She was shaken by her diagnosis and became determined to adopt a more healthful diet. She changed her diet from “healthy western” to whole food plant-based (). She also started supplemental vitamin B12. She lost 22.7 kg in <6 months, resulting in a BMI of 35.1 kg/m2. Her diabetes resolved, with her hemoglobin A1c falling to 5.7% without the use of diabetes medications. Her baseline dyspnea on exertion improved considerably. Repeat echocardiography in November 2017 revealed a normal left ventricular ejection fraction of 55% ().
Although causality cannot be determined, this case highlights the potential role of a plant-based diet in helping to reverse systolic dysfunction, or heart failure with reduced ejection fraction.
This article will review how a minimally processed whole food plant-based dietary pattern and similar dietary patterns, such as the Dietary Approach to Stop Hypertension (DASH) diet and vegetarian diet, may contribute to the reversal of left ventricular dysfunction. For the purposes of this case report and literature review, the term plant-based diet will include dietary patterns that are exclusively plant-based and dietary patterns that are predominantly plant-based, such as the DASH diet and vegetarian dietary patterns. |
pmc-6579896-1 | A 57-year-old asymptomatic man was found to have multiple intestinal masses by computed tomography (CT) done as part of his routine medical examination in December 2011. Surgical resection (R0) was performed in December 2011. The resected specimen consisted of a mass measuring 10.0 ×10.0 cm in maximal diameter. Final pathologic diagnosis revealed a high-risk GIST according to the Armed Forces Institute of Pathology (AFIP) criteria (). The patient was not treated with adjuvant treatment after surgery in the local hospital because he had difficulty paying for adjuvant imatinib therapy. On routine follow-up visit in May 2012, local recurrence and metastasis were confirmed by imaging. He was then referred to West China Hospital in May 2012.
Beginning in May 2012, this patient received first-line imatinib orally with a dose of 400 mg/day resulting in a partial response. Disease progression occurred after the continuation of imatinib for 54 months. The patient was then treated with cytoreductive surgery combined with imatinib and showed a PFS of 7 months. New biopsy of an abdominal metastasis yielded a KIT mutation in exon 11 as well as in KIT exon 13 (V654A), confirming the clinical observation of secondary imatinib resistance (). In May 2017, this patient received second-line sunitinib. After 11 months of treatment, sunitinib was discontinued due to disease progression. The patient refused biopsy for additional mutational analysis for personal reasons.
Although regorafenib had been approved for the third-line treatment of patients with advanced GISTs by China Food and Drug Administration at that time, the patient refused the agent due to the cost and budget constraints. In the meantime, there was a medical-product-donating project for apatinib that patients could get support since they were enrolled in a clinical trial. After signing informed consent, the patient was treated with apatinib 500 mg daily beginning in April 2018. Abdominal CT scans before apatinib therapy showed the metastatic lesions in the abdomen and pelvic cavity (). The drug was well-tolerated, and after 2 months of treatment, the patient had a stable disease (SD) on CT according to RECIST 1.1 (). On routine follow-up in December 2018, the CT scan showed that the lesions were similar to the latest images, confirming a SD after 8 months of treatment with apatinib ().
During apatinib treatment, this patient developed primary side effects of hypertension (grade III) and proteinuria (grade II) according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (). Both adverse events were well-controlled with drug treatment.
On the last routine follow-up visit in December 2018, the patient is still taking apatinib as a single agent for maintenance therapy with mild toxic effects. Both clinical and imaging evaluation demonstrated no evidence of disease progression. The PFS time is more than 8 months. This study was approved by the Institutional Review Board of West China Hospital, Sichuan University (ChiECRCT-20170095). The patient gave written informed consent in accordance with the Declaration of Helsinki. |
pmc-6579935-1 | A 64-year-old female patient was referred to our hospital with an aneurysm of the right internal carotid artery bifurcation. The aneurysm was diagnosed by magnetic resonance angiography (MRA) performed at the referring hospital after an episode of impaired vision. Using a diagnostic digital subtraction angiography (DSA) including a rotational 3D angiography the aneurysm morphology could be visualized in detail. Additional aneurysms were ruled out. The average aneurysm diameter was 2.9 mm with a maximum diameter of 3.1 mm measured in the lateral projection. The maximum aneurysm height was 3.2 mm (Fig. ). The case was discussed in an interdisciplinary neurovascular board resulting in the recommendation for an endovascular treatment. After a comprehensive explanation of the risks and benefits, the patient decided for the suggested treatment strategy. The broad based longish morphology made this aneurysm suitable for treatment with a WEB device, although the angulation between the aneurysm and the carotid artery was very tight with a rostrally positioned inclination of the aneurysm (Fig. a).
According to our institutional standard the patient was placed on dual antiplatelet therapy 5 days prior to the procedure in order to obtain a bail out option including the placement of a stent. The procedure was carried out with the patient under general anesthesia. A coaxial guiding catheter combination (Neuron™ MAX 6F, Penumbra, Alameda, CA, USA) and Navien™ 072 (Medtronic, Irvine CA, USA) were positioned in the cervical segment of the right internal carotid artery. Size selection of the WEB device resulted from exact calibrated measurements of the aneurysm in two orthogonal projections based on a 3D rotational angiographic dataset according to the established standards described in the literature []. A WEB SLS device, the more spherical version of the WEB with a 4 mm width, was chosen in the particular case. A VIA 17 microcatheter (MicroVention) was placed in the center of the aneurysm followed by the implantation of the WEB device. Once the WEB was completely unsheathed from the microcatheter an angiographic run documented the appropriate position of the device inside the aneurysm without any compromise of the parent artery (Fig. b). A further angiographic run 10 min later confirmed the stable position of the device. The device was than electrothermally detached with the distal marker of the microcatheter placed towards the detachment zone of the WEB. The detachment from the insertion wire was without problems. The cautious withdrawal of the microcatheter resulted in a dislocation of the WEB device outside the aneurysm into the middle cerebral artery. The next angiographic run documented a further dislocation of the device that was now locked inside the bifurcation of the middle cerebral artery (Fig. ).
Now a Rapid Transit microcatheter (Codman, Norderstedt, Germany) was advanced towards the dislocated WEB device with a Traxcess EX microwire (Microvention). The microwire was pulled back and the Alligator retrieval device was inserted into the microcatheter and pushed forward. Once the closed jaws of the device reached the distal marker of the microcatheter both the microcatheter and the device were pushed towards the struts of the WEB device. Now the Alligator retrieval device was slightly advanced and the microcatheter was held in place, which resulted in an opening of the four jaws of the Alligator device at the level of the dislocated WEB. The microcatheter was then slightly advanced under permanent distally directed tension of the Alligator retrieving device in order to close the jaws. At this point the ensemble of the microcatheter with the Alligator was gently pulled back with the WEB device trapped between the jaws (Fig. ).
A final angiographic run proved an unchanged situation especially without suspicion of a dissection followed by the described maneuver. The procedure was finished without a final treatment of the aneurysm and 5 days later the aneurysm was occluded with coils using the remodeling technique. |
pmc-6580147-1 | A 50-year-old man visited our hospital with pain in his neck that had lasted for 6 months. The patient felt pain with paraesthesia in both his shoulders that radiated to his fingers. The pain occurred intermittently and mostly during activities. There was no prior history of trauma. For 5 months, the pain and paraesthesia worsened, and he complained of weakness in both lower extremities. The patient then sought medical advice from a neurosurgeon who said that there was nerve entrapment and advised him to undergo laminoplasty. At that time, he refused to undergo surgery because he was unable to make a decision. For 4 months, the patient underwent physiotherapy; however, there was no improvement. The patient subsequently visited our hospital where he was advised to undergo laminoplasty. He worked as a contractor and mostly sat behind a desk. He had no history of diabetes or hypertension. He denied any decrease in body weight or appetite, and there was no history of chronic cough.
On physical examination, his general condition was unremarkable (). There was no tenderness on palpation along the midline. Examination of the cervical spine showed positive L'hermitte test, finger-escape test, grip-and-release test, Hoffman-Trommer sign and Spurling sign. The patient was able to move his neck normally. Further examination revealed diminished motoric strength in all extremities with positive Babinski reflex and clonus with normal patellar and Achilles tendon reflexes. He had urinary retention and faecal incontinence.
The patient underwent radiographic examination that showed straight cervical with mid-sagittal diameter of 10 mm and a Torg ratio of 0.37 (). There was osteophyte, endplate irregularity and disc-space narrowing at C4-C5 levels with spur formation at C3 through C5. Magnetic resonance imaging (MRI) examination showed cervical canal stenosis at C4-C5 levels and spinal cord compression (). Laboratory findings were unremarkable except for leukocytosis.
The patient was diagnosed with cervical canal stenosis due to cervical spondylotic myelopathy at C4-C5 vertebrae, with a Japanese Orthopaedic Association (JOA) Score of 11. He underwent decompression and posterior stabilisation with open-door laminoplasty under general anaesthesia. Two months after the operation, the patient felt no pain in his neck or fingers. He was able to function normally, and the weakness disappeared. The patient was able to defecate and urinate normally. The JOA score after surgery improved to 17. |
pmc-6580185-1 | Our patient is a 42-year-old woman with AML diagnosed in August 2018 after 3 months of non-specific symptoms, including recurrent herpes infections, headaches, and fatigue. Her first induction chemotherapy was with idarubicin, an anthracycline, and cytarabine (a synthetic pyrimidine analogue). After several days of therapy, she developed neutropenia and severe diarrhea due to mucositis, leading to hypophosphatemia and hypokalemia. The patient was treated for fever in neutropenia initially with cefepime and amikacin and then with piperacillinum/tazobactam due to a presumed allergic reaction to cefepime or amikacin. Because of persistent fever, piperacillinum/tazobactam was switched to meropenem, and because of the severe mucositis, caspofungin was added. Persisting symptoms and rising inflammatory parameters over the next days led to further investigations. On chest CT scan, five small pulmonary nodules (measuring less than 4 mm) were detected. This finding together with the associated febrile neutropenia led to the suspicion of pulmonary aspergillosis. Her antifungal therapy was switched from caspofungin to intravenous, and then to oral voriconazole. Voriconazole trough concentration measurements were within the therapeutic range (1–6 mg/L). Under treatment with additional broad-spectrum antibiotics (meropenem, aztreonam, and vancomycin due to multiple bacterial infections), she showed a good clinical response. Ten days after starting voriconazole, however, her liver transaminases rose, accompanied by only slightly elevated cholestatic parameters and normal bilirubin levels (). After 3 weeks of voriconazole therapy, alanine aminotransferase (ALT) (reference range, 8–41 U/L) reached its peak value of 1793 U/L, and antifungal therapy was terminated. Aspartate aminotransferase (AST) (reference range, 11–34 U/L) reached a peak value of 672 U/L on the same day. Alkaline phosphatase (ALP) (reference range, 35–105 U/L) values oscillated from 80 U/L up to nearly 200 U/L, reaching a peak value of 197 U/L after about 2 weeks of treatment. Cessation of the triazole administration led to a normalization of the LFTs. Due to their different half-lives in plasma, AST normalized first, followed by ALT, and then the cholestatic parameters.
Six weeks later, the patient received the second course of induction chemotherapy. After several days of treatment with the nucleoside analog cytarabine and amsacrine, a synthetic topoisomerase II inhibitor, the patient again developed severe diarrhea and fever in neutropenia. Two sets of blood cultures grew Streptococcus mitis. Broad-spectrum antibiotics were commenced (cefepime, ceftriaxone, and piperacillin/tazobactam). Caspofungin was administered to treat the suspected pulmonary aspergillosis. After 1 week of caspofungin treatment and stable LFTs despite chemotherapy, antifungal therapy was switched to oral posaconazole tablets for better coverage of mucor species. On the first day, 300-mg oral posaconazole was administered twice daily as a loading dose, followed by 300 mg daily for 5 days. A low posaconazole blood concentration on treatment day 4 (0.5 mg/L; target range, 1.26–3.74 mg/L) prompted a dose increase to 400 mg once daily on day 6. After 4 days of posaconazole treatment, liver enzymes began to rise ().
Posaconazole was discontinued and therapy switched to caspofungin again. However, despite this, transaminases continued to rise (). Our department of clinical pharmacology and toxicology was consulted and asked to investigate the cause of the rising liver enzymes and to make suggestions for the further management. ALT was 179 U/L at that time, whereas ALP and bilirubin remained normal. We systematically worked up all drugs administered over the past months, evaluated their potential hepatotoxicity [. Bethesda: Food and Drug Administration; c2019 (cited 2019 Mar 01). Available from: ], determined temporal associations, and assessed differential diagnoses. Therapeutic drug monitoring (TDM) was performed three times for voriconazole and once for posaconazole. All serum concentrations were within the therapeutic range. Abdominal CT scans revealed no signs of liver or portal vein thrombosis, masses, hepatic steatosis, or biliary obstructions. Serology showed no signs of viral infections, and eosinophils were within normal limits on complete blood count, incongruous with the diagnosis of “drug reaction with eosinophilia and systemic symptoms” (DRESS) (Walsh and Creamer, ) but difficult to interpret due to aplasia under chemotherapy. On account of the low thrombocyte count, a liver biopsy was not performed. Altogether, we concluded that voriconazole and posaconazole most likely caused both episodes of liver enzyme elevation.
AST reached its peak value of 130 U/L 6 days after the last posaconazole administration followed by ALT (peak value of 502 U/l) on the following day. Gamma-glutamyltransferase (GGT) (reference range, 6–40 U/L) was only slightly increased (97 U/L); ALP and bilirubin again remained within normal limits. Over the next days, LFTs returned to baseline and the patient responded clinically too. Chest CT scan was repeated before discharge. Over the preceding 2 months, the five pulmonary nodules had increased considerably in size, strengthening the suspicion of pulmonary aspergillosis. Our infectious diseases specialists recommended one of two remaining treatment options: continuation of caspofungin, given intravenously once daily, or initiation of isavuconazole (Cresemba®) 200 mg once daily orally. Unfortunately, several organizational and actuarial reasons made once daily infusions after discharge impossible. The patient was informed about the risk of hepatotoxicity with isavuconazole, possibly resulting in severe and dangerous liver damage. Nevertheless, after burdensome therapies and many weeks of hospital stay, she decided to take isavuconazole and repeatedly have her LFTs monitored. During the first weeks of treatment with isavuconazole, transaminases steadily decreased, and the patient improved clinically (). After 5 weeks of continuous treatment, 2 days before the planned allogenic hematopoietic stem cell transplantation (allo-HSCT), ALT and AST began to rise again. Seven weeks after successful isavuconazole treatment, the drug had to be stopped. Transaminases rose for another 1.5 weeks before returning to baseline, similar to posaconazole.
The allo-HSCT was successful. Interestingly, our patient as well as her donor—a blood relative—were both carriers of a rare HLA class I antigen (B*35:02, found in only 0.912% of the Caucasian population) [. Ulm: The ZKRD. The German National Bone Marrow Donor Registry [Internet]. Ulm: The ZKRD. 1992 - [cited 2019 Mar 4]. Available from: . The patient recovered rapidly after the allo-HSCT. Favorable clinical findings concerning the aspergillosis led to a de-escalation of the antifungal treatment to prophylactic dose fluconazole (400 mg orally once weekly). We reported the adverse drug reactions—DILI under voriconazole, then posaconazole, and then isavuconazole—to the national drug authority’s department of pharmacovigilance (Swissmedic). |
pmc-6580309-1 | A 6-month-old girl presented to the pediatric emergency department with four days of intermittent fever, tachypnea, and persistent cough. According to the patient’s mother, she had not experienced previous nausea, vomiting, dyspnea, or peripheral edema; but she did exhibit poor oral intake and general failure to thrive. Her mother reported no history of trauma, birth complications, or evidence of other congenital malformations and a thorough review of systems was otherwise negative. Her mother was a 23-year-old woman who denied any personal or family history of chronic disease, sick contacts (including anyone infected with tuberculosis), and reported a negative HIV status. She was seen by a physician prenatally but did not receive routine ultrasound.
Physical examination revealed a small female infant with low body weight (4.8 kg, <5 percentile weight for age), breathing at a rate of 52 breaths/min, with a heart rate of 145 beats/min, and blood pressure of 126/111 mmHg. She was afebrile. Abdominal evaluation was soft and nontender. Chest auscultation was notable for diffuse bilateral rhonchi and rales, though cardiac sounds were normal. She was not cyanotic. Preoperative labs demonstrated anemia (HgB: 10.2 g/dL) but no leukocytosis (WBC: 9.4 × 103/μL). Echocardiography was reported as normal. An initial chest radiograph () showed dilated loops of bowel located centrally in the thoracic cavity, obscuring the cardiac silhouette, with opacification of the lower lobe of the left lung. These findings were suspicious for CDH, which was confirmed by a thoracic CT scan (). Plans for corrective surgery were made with the preoperative diagnosis of a likely Morgagni-type CDH.
The patient was taken to the operating room and underwent a left thoracotomy. It was readily apparent that there was no hernia sac or loops of bowel within either pleural cavities. However, the pericardium was grossly enlarged and ballotable. We carefully incised the pericardium, from which drained roughly 20 ml of serous fluid. Within the pericardium we found the hernia sac, which was also incised, revealing loops of small bowel that were incarcerated, but not strangulated (). The heart itself was visualized directly without overlying pericardium. On two occasions during manipulation of the hernia contents the heart became asystolic. Each time systole was quickly restored with direct cardiac massage. We proceeded to reduce 10 cm of small bowel, and corrected the 2 cm defect in the cardiac portion of the central tendon of the diaphragm. The remainder of the diaphragm was intact, the abdominal wall was intact, the great vessels entering and leaving the heart were grossly normal, and we found no evidence of any other congenital malformations within the thorax. We closed the pericardium, leaving a small defect to prevent future pericardial effusion. We subsequently closed the thoracic cavity in layers, leaving a 28 French chest tube draining the pleural cavity by gravity under water seal.
Postoperative management included treatment with furosemide for acute pulmonary edema on post-operative day one. On the second post-operative day, the patient developed a new leukocytosis and fever. A chest radiograph demonstrated bilateral opacification of the lung fields. She was given penicillin, acetaminophen, and salbutamol and a follow-up chest radiograph demonstrated clear lung fields and no evidence of hernia. The patient was discharged seven days after her operation, breastfeeding normally clinically stable. Despite attempts to contact the mother, the patient was lost to follow up and not seen in our surgical clinic. |
pmc-6580311-1 | We report a sixty-two year old female with myelodysplastic syndrome that converted to acute myeloid leukemia. After initiation of induction chemotherapy with Vyxeos, she developed neutropenic fever with enteritis for which she underwent sigmoidoscopy on cycle 1 day 35 of Vyxeos which showed diverticulosis (). Biopsy revealed no fungal elements and minimal inflammation. She was readmitted approximately one month later for haploidentical stem cell transplantation (HSCT). Prophylactic posaconazole started on day +5 post HSCT. Her hospital course was prolonged due to delayed engraftment with ongoing neutropenia. Four weeks post-transplant she started experiencing abdominal pain and decreased stool output on day +26. Abdominal computed tomography (CT) demonstrated a 4.9 cm perirectal abscess on day +30 (). Cytology of the abscess aspirate revealed aseptate fungal hyphae concerning for mucormycosis (). (1,3)-β-D-glucan and galactomannan assays were negative. Her absolute neutrophil count had begun to increase up to 900 and she had been taking prophylactic posaconazole prior to HSCT. CT imaging of the sinuses, head and chest were obtained and revealed no other foci of infection. Liposomal amphotericin B at 5mg/kg/day intravenously was started on day +30 with cessation of posaconazole on day +30. Additionally, micafungin 100mg intravenously daily was initiated on day +34.
Fungal isolate from the fungal culture was sent to the University of Texas Health Science Center at San Antonio Fungus Testing Laboratory for species identification. For molecular identification, portions of the culture were suspended in Buffer G2 (Qiagen, Valencia, CA) followed by lysing using a bead beater instrument (Precellys Evolution, Bertin Instruments, Rockville, MD). Proteinase K was added, incubation occurred at 56 °C, and the DNA was extracted using an EZ1 DNA tissue kit with a BioRobot EZ1 instrument (Qiagen). The internal transcribed spacer region (ITS) and D1/D2 rRNA gene were then amplified by polymerase chase reaction using previously described primers [, , ]. The PCR products were sequenced, assembled, and analyzed using Sequencher software version 5.4.6 (Gene Codes, Ann Arbor, MI), and the sequences were queried in GenBank using the BLASTn algorithm at the NCBI website (). The ITS sequence demonstrated 100% identity to Rhizopus arrhizus (GenBank Accession No. ; base pair match 570/570), and the D1/D2 sequence also showed 100% identity to Rhizopus arrhizus (GenBank Accession No. ; base pair match 636/636). Further barcode analysis of the ITS sequence demonstrated that the isolate was Rhizopus arrhizus var. arrhizus [].
The patient underwent a proctosigmoidectomy with colostomy to remove the fungal abscess on day +33. The post-operative diagnosis was fungal diverticulitis (). However, six days (day+39) following surgery she had return of fevers and abdominal pain. Repeat abdominal CT showed recurrence of the fungal abscess despite surgical excision and continued antifungal therapy. Given the high likelihood of poor surgical outcome for repeat debridement and likely need for pelvic evisceration, the patient declined further intervention. She was discharged to hospice with palliative isavuconazole on day +40. She was loaded with 6 doses oral isavuconazole 375mg every 8 hours followed by daily oral isavuconazole 375mg. However, the patient remained clinically stable on isavuconazole, and repeat imaging 4 months (day + 105) following discharge demonstrated interval improvement of the abscess though without complete resolution (). The patient is currently clinically well and on hospice 7 months after her Rhizopus Arrhizus diverticulitis diagnosis and routinely followed in the outpatient bone marrow transplant clinic without serum isavuconazole level checks. |
pmc-6580323-1 | Herein, we report a case of a 42-year-old female, medically free, with 5 previous normal vaginal deliveries, last delivery was 1 year prior to presentation. She was in her usual state of health until she presented to our emergency department complaining of sudden left iliac fossa and periumbilical pain associated with nausea and constipation for 1-day. The pain was not radiating with no aggravating or relieving factors. There was no fever, dysuria, hematuria or vaginal discharge. Her menstrual period was regular. She had no history of hypercoagulability or previous thromboembolic events as well as no history of previous surgery. Upon examination, she was afebrile & hemodynamically stable. Abdominal examination revealed left lower tenderness with guarding, with no palpable masses nor organomegaly. Her pelvic examination was unremarkable. Laboratory investigations showed no leukocytosis, negative C-reactive protein & Beta human chorionic gonadotropin with normal coagulation profile & a negative urine analysis. Transabdominal ultrasound of the left ovary showed dilated left ovarian vein ( A & B). Doppler abdominal ultrasound showed a dilated left ovarian vein with absent flow. Computed Tomography (CT) scan with contrast was done and revealed a thrombus in the left ovarian vein (A–C). Therefore, the diagnosis of OVT was made and the patient was started on low molecular weight heparin followed by warfarin for 6 months and discharged home after 1 week. She was followed up regularly for 1 year by Doppler ultrasound which showed complete resolution of the thrombus (). |
pmc-6580326-1 | We present a case involving a 76-year-old female patient who was first seen by her doctor for problems and discomfort with deglutition. Upon an objective examination, the thyroid gland appeared to be mildly enlarged (more on the right side of the neck) with a hard consistency, but mobile relative to the underlying tissues. The only comorbidity was a mental illness.
An ultrasound (US) of the neck was immediately performed and revealed a multinodular retrosternal goiter, for which the larger nodule in the right lobe presented with a diameter of approximately 6 cm and complete ring calcification. The goiter extended into the upper mediastinum and was lying on the aortic arch.
Due to the goiter’s retrosternal configuration, we performed a CT scan of the neck and thorax. The scan showed the posterior dislocation of the epiaortic vessels and lateral dislocation and compression of the pharynx. The large nodule described previously based on US exhibited a mixed type of calcification; in fact, in the context of a large egg-shell calcification, multiple spots with microcalcifications were observed (A and B).
Given the notable dimensions of the goiter, its symptomatic disposition and the extreme calcification of the nodule, we chose to avoid an ultrasound-guided ago-biopsy due to the low probability of obtaining a good tissue sample and the consequent diagnosis, and in agreement with the patient’s endocrinologist, we decided to directly perform a standard thyroidectomy through a cervicotomy. The primary difficulty during the operation was the complete calcification of the entire right lobe, which was adherent to the trachea and vascular structures (A and B). However, no major bleeding or complications occurred during surgery.
Macroscopically, the pathologist described a nodule with a weight of 130 g that was partially cavitated and extremely hard when cut (A and B).
A microscopic histological examination excluded the presence of atypical cells and revealed nodular hyperplasia in fibrotic areas.
The patient’s postoperative course did not involve any complications related to the surgical procedure, and she was discharged two days after the surgery. |
pmc-6580434-1 | A 26-year-old male presented with complaints of acute onset right iliac fossa pain associated with nausea and vomiting for 4 days. On clinical examination, right iliac fossa tenderness was present. Blood investigations were within normal limits. Ultrasonography revealed presence of mild free fluid in the right iliac fossa. Appendix could not be visualized. On contrast enhanced computed tomography (CECT) abdomen and pelvis, there was presence of free fluid in the right iliac fossa with thickening of the right conal fascia and omental fat stranding (). The lumen of the appendix was patent and the tip of the appendix appeared to be thickened. Based on these findings, clinical diagnosis of acute appendicitis was made and patient was planned for laparoscopic appendectomy.
On laparoscopy, about 200 ml of hemorrhagic fluid was present in the right iliac fossa and pelvis. A segment of the omentum adjoining the cecum appeared dusky, congested and partially infarcted while the rest of the omentum was normal in appearance (). Grossly, appendix, cecum and terminal ileum appeared normal (). Laparoscopic appendectomy with excision of the diseased part of the omentum was performed. Postoperative recovery was uneventful with two days of hospital stay. On histopathology, appendix was normal with lymphoid hyperplasia while omental specimen showed areas of congestion, hemorrhage and inflammation. |
pmc-6580457-1 | A 66-year old male patient presented to the emergency department with pain in the lower abdomen and a temperature of 38.6 °C. One week previously, after an incisional hernia repair, he had required a urinary catheter due to urinary retention. His past medical history was significant for a transcatheter aortic valve implantation (TAVI) due to a severe aortic stenosis 1 year earlier, and psoriasis vulgaris. On admission, the patient had a transurethral urinary catheter in place. The physical examination was normal, except for a febrile temperature and lower abdominal pain. The C-reactive protein was only mildly elevated to 16 mg/L (normal range < 10 mg/L), and mild pyuria (10–20 leucocytes per field of view) and hematuria (5–10 erythrocytes per field of view) were present. A catheter-associated urinary tract infection was suspected. Treatment with intravenous ceftriaxone (2 g qd) was initiated and changed after 3 days to intravenous amoxicillin-clavulanate (2.2 g tid). The patient continued to spike fevers up to 39.8 °C. Initial blood cultures were negative, but a repeated set of blood and urine cultures on day four was positive for P. aeruginosa (susceptible to all antibiotics tested, including piperacillin-tazobactam and ceftazidime). The antibiotic treatment was changed to intravenous piperacillin-tazobactam and later to ceftazidime. CT scans of the thorax and abdomen were unremarkable. A trans-esophageal-echocardiography (TEE) requested because of persistent fever, did not reveal any vegetation on the heart valves or other signs of infective endocarditis. Repeated blood cultures on day 15 were again positive for P. aeruginosa. However, now, susceptibility testing indicated resistance to piperacillin-tazobactam and ceftazidime. The treatment was changed accordingly to meropenem and gentamicin. Besides a mild fatigue, the patient had no localizing symptoms, and repeated TEE and abdominal and thoracic CT scans did not reveal any focus of infection. P. aeruginosa isolated from a blood culture on day 19 showed additional resistance to cefepime. On day 31, P. aeruginosa isolated from another blood culture changed its resistance profile one more time, now being again susceptible to piperacillin-tazobactam, ceftazidime and cefepime, but resistant to carbapenems. Antibiotic therapy was switched to cefepime and gentamicin. An 18FDG-PET/CT was not able to identify any focus of infection. After 5 weeks, the patient was transferred to a tertiary care university hospital. On day 40, a free-floating mass (12 × 8 mm) was identified on the aortic valve on TEE examination, and P. aeruginosa prosthetic valve endocarditis was diagnosed (Fig. ). At this point, the patient was still febrile. Laboratory studies showed a leukocyte count of 8.9 × 109/L (normal range 3.5–10.0 × 109/L) and a C-reactive protein of 66.2 mg/L. The following day the patient successfully underwent surgical prosthetic valve replacement. The culture of the removed valve was positive for P. aeruginosa. Definitive antibiotic therapy consisted of intravenous cefepime, tobramycin and ciprofloxacin for additional 6 weeks (Fig. ). The patient recovered quickly after the valve replacement and left our hospital for rehabilitation 9 days after surgery. He was doing well at the 3-month follow-up.
P. aeruginosa isolates from blood cultures at day 31 and from the culture of the removed valve at day 41 were analyzed using whole genome sequencing (MiSeq Illumina). No genetic differences could be detected between the two isolates (cgMLST showed zero allelic differences, both strains are ST 244), providing clear evidence that the P. aeruginosa isolates from the blood and the aortic valve were from the same strain. We could genotypically detect mutations in the following genes: transcriptional AmpR and beta-lactamase expression regulator AmpD, both linked to resistance against ceftazidime and piperacillin-tazobactam. In addition, we could also detect a mutation in OprD, which is linked to carbapenem resistance. This correlates with the phenotypic findings and is in line with findings in the literature. Unfortunately, the P. aeruginosa isolated from the first three positive blood cultures had already been discarded and were not available for further analysis (Fig. ). |
pmc-6580493-1 | A 64-year-old immunocompetent man presented to the outpatient clinic of Department of Neurosurgery, complained of a worsening pain of waist and left lower extremity, accompanied by numbness and paresis of bilateral lower extremity for 20 days. 7 months before admission, he took a biopsy of left groin mass, the pathological diagnosis was non-Hodgkin small B cell lymphoma. Immunohistochemical staining demonstrated the typical cells with CD5(+), CD20(−), Pax-5(+), Bcl-2(+), CD3(+), CD23(−), CyclinD-1(−), Ki-67(+ > 50%). According to the diagnosis, he underwent a standard CHOP chemical therapy immediately, and got a partial remission during the following 7 months, inguinal lymph nodes regressed by more than 50% and no new enlarged lymph node was detected by ultrasound examination. About 10 days after the last CHOP, he got a persistent pain in the waist and left thigh, accompanied by numbness and paresis, the symptoms had rapidly progressed to both lower extremity and left him wheelchair bound in 20 days, then he came to our department for further treament.
Physical examination demonstrated spastic paralysis of the left lower limb and hypesthesia of bilateral lower limb under L4 level, he also got tendon hyperreflexia and Babinski sign positive in the left side, with bladder dysfunction.
Before admitted to our hospital, he took a whole-body F-18 FDG-PET/CT scan, which showed L3 level intrathecal FDG high uptake(Fig. a,b,d,e,g,h), without abnormal FDG uptake of other parts of central nervous system and the rest of the body, suggested probable involvement of lower spinal cord. Lumbar Gd-enhanced MRI showed L3 level multiple intrathecal lesions with isointense on T1WI and hypointense on T2WI, with remarkable homogenous enhancement. The total size of the lesions was about 2.29*1.39 cm with clear border, cauda equina was compressed badly. In the image of F-18 FDG-PET/CT, only 2 nodules could be distinguished, but in the high resolution MRI, especially T2WI image, we could distinguish as many as 7 (Fig. a-i).
In consideration of the previous history, physical and image examination, we got a pre-operation diagnosis of secondary cauda equina lymphoma. A spinal canal decompression and tumor resection was performed 2 days after admission because the symptoms progressed rapidly, the patient developed complete paralysis and acute urinary retention. During the operation, we found the cauda equina was swollen and compressed badly, as many as 11 subdural-extramedullary bean-size nodules involving several nerve roots were found (Fig. ). The nodules were red and with complete capsule, the relationship of tumors and cauda equina were too close to dissect, so we had to cut off the involved nerve roots to remove all the 11 nodules.
The paralysis of his left leg recovered rapidly since the operation, at the second day after operation, muscle strength was grade 2, and at the 7th day after operation, the patient could stand with assistance, only mild hypesthesia of the left leg remained. Post-operation MRI + C showed complete resection of the lesions with sufficient decompression. Pathological diagnosis was diffuse large B cell lymphoma, immunohistochemical stain showed CD20(+), Pax-5(+), CD3(+/−), Vimentin(+), NeuN(−), CD99(−),GFAP(−), S-100(−), Ki-67(+ > 50%), CK(−), CD56(−) Synaptophysin(−), TIF-1(−). The patient was transferred to the department of hematology at the 14th day after operation for further R-CHOP chemotherapy.
During the follow-up period of more than one year since the operation, the patient went on standard R-CHOP chemical therapy. He got a partial bladder function recovery at the 4th week after the operation, and could walk slowly without assistance by then, no new symptom of spinal cord was detected. A lumbar MRI + C at the 9th month showed no evidence of recurrence in situ (Fig. p-r). But at the 13th month, he visited the emergence room with severe headache and vomit, he was in such a bad condition that he was unable to stand MRI or F-18 FDG-PET/CT. Enhanced CT showed giant mass in bilateral frontal lobes with remarkable homogenous enhancement, circled by extensive brain edema, which obviously meant recurrence of the NHL. The patient and his family refused any further treatment, and finally he died in the following 2 weeks because of brain herniation. |
pmc-6580498-1 | A 30-year-old Chinese male was admitted to the local hospital with a history of intermittent muscle weakness for over 3 years. He was found with high blood pressure (170/118 mmHg), hypokalemia (2.0 mmol/L), normal thyroid function, and bilateral adrenal masses on computed tomography (CT). He had no history of alcohol or drug abuse, in particular, no history of steroid usage, and no family history of endocrine diseases or malignant tumors. He was treated with a temporary prescription of nifedipine, potassium chloride controlled release tablets, and was referred to our hospital for further investigation.
Upon admission to our hospital on August 11, 2016, physical examinations revealed blood pressure of 153/100 mmHg and pulse rate of 76 beats per minute. His body mass index was 29.1 kg/m2, height 176 cm, weight 90 kg, and waist circumference 98 cm. There were no specific findings on chest or abdominal examination and his muscle power was normal. No edema of the lower extremities was noted and he had no Cushingoid features (i.e., moon face, purple striae, or hirsutism) except slight central obesity.
Routine laboratory tests revealed an extremely low serum potassium (2.12 mmol/L) with relatively high urinary potassium (38.66 mmol/24 h). Twenty-four-hour urinary free cortisol was 140.7 μg and 137.7 μg on two separate occasions (reference range: 20.26–127.55 μg/24 h). Detailed relevant biochemical and endocrinological findings are shown in Table . His aldosterone-to-renin ratio (ARR) was within normal range after discontinuation of nifedipine for more than 2 weeks, when drug-induced false-negative results were likely eliminated. Thus, further screening for PA was not performed (Table ) []. In overnight and standard low-dose dexamethasone suppression tests, dexamethasone failed to suppress endogenous cortisol secretion, indicating CS (Table ). Adrenal CT scan revealed one round, homogeneous, low-density mass in each adrenal gland. The mass on the right was 19 × 14 mm while the one on the left was 25 × 15 mm (Fig. ). Bilateral AVS was performed to lateralize the functional side. Concentrations of plasma aldosterone and cortisol were measured in specimens from both adrenal veins (AV) and the inferior vena cava (IVC), and corrected by concentration of plasma epinephrine. As shown in Table , epinephrine concentrations in both AVs were approximately 10-fold higher than that in the IVC, suggesting successful adrenal venous catheterization. Notably, at > 200 ng/dL, the aldosterone concentration in the right adrenal vein was markedly higher than those in the LAV and the IVC, suggesting excess secretion of aldosterone from the right adrenal mass. Additionally, 7701 nmol/L, the cortisol concentration in LAV was 12.81-fold higher than that in the RAV and 27.4-fold higher than that in the IVC, suggesting excess secretion of cortisol from the left adrenal mass. Thus, with AVS, hypersecretion of cortisol from the left adrenal tumor and that of aldosterone from the right tumor was identified. |
pmc-6580501-1 | Our patient’s mother, 22-year-old previously healthy multigravida woman (Para 4, Gravida 6, Abortion 1, Live children 4) was admitted to the Beni General Hospital Ebola Treatment Center 2 days after onset of symptoms (fever, vomiting and malaise) and was confirmed positive for EBOV by polymerase chain reaction (PCR). She reported a 34 week pregnancy and confirmed that the previous pregnancy follow up was uneventful. She was discharged after 1 week of management made of rehydration, Cefixime, Paracétamol and other supportive measures.
At the gestational age of 38 weeks, vaginal delivery occurred after a 10 h labor, the foetus was in breech presentation with meconial amniotic fluid and a normal placenta. The female newborn baby did well initially with an Apgar score of 8/9/10. General and neurologic examination did not reveal any pathology. The vital signs and anthropometric parameters at birth were as follows: temperature 36.5 °C, regular breathing at 52 cycles per minute and heart rate 146 beats per minute; weight of 3500 g, head circumference of 36 cm and height of 53 cm. The haemoglobin level was 16 g / dl; the umbilical cord blood PCR, the blood and salivary swabs were negative for the Ebola virus disease. She was subjected to an antibiotic therapy made of cefotaxime (3x200mg/day) and was discharged after 5 days.
At 1 month and 6 days of age, the baby was growing normally, she weighed 4100 g (versus 4400 g ideally), she was being breastfed and her mother reported no illness in the past days of her life. |
pmc-6580543-1 | During a hot afternoon in July, a 48-year-old man developed symptoms, such as nausea, vomiting, headache, chest tightness, and shortness of breath, while working outdoors for 2 h in a southern city in China. The outside temperature at that time was 35 °C. Notably, the patient lived in the north part of China and had traveled to the southern part when he was sick. After 15 h, he went into coma and was then transferred to the emergency department of the hospital. The patient was in good health before the onset of the disease. Upon arrival, the temperature of the patient was 40.2 °C, blood pressure was 75/40 mmHg, and pulse rate was 100 beats/min. His blood oxygen saturation under balloon-assisted ventilation was 95%. Laboratory tests indicated rhabdomyolysis syndrome, acute kidney injury, hepatic disfunction, hyperkalemia, and metabolic acidosis. The serum D-dimer level of the patient was elevated at 1022 (normal range: 0–232) μg/L. Therefore, the patient was diagnosed with HS. He was immediately treated with a cooling blanket and plasma exchange and received assisted ventilation. Brain CT scans performed on the 3rd day of admission showed symmetrical low-density lesions in the bilateral basal ganglia. On the 7th day of admission, the patient’s state of consciousness improved. However, he experienced blurred vision. Eye examination results were normal. Brain magnetic resonance imaging (MRI) was performed 8 days after admission. Cerebral MRI revealed a slight hyperintensity in the bilateral putamen on diffusion-weighted imaging (DWI) sequence and bilateral symmetrical hypointensity in the middle of the putamen and hyperintensity around hypointensity on the apparent diffusion coefficient (ADC), fluid-attenuated inversion recovery (FLAIR), and T2-weighted imaging (T2WI) sequence. The lesions showed hyperintensity in the middle of the bilateral putamen and hypointensity around them on T1-weighted imaging (T1WI) sequence (Fig. A-E). Magnetic resonance venography (MRV) in sagittal projection performed on the 12th day of admission showed the absence of a straight sinus and vein of Galen, indicating CVT. In addition, the lack of flow signal was also found in the distal part of the superior sagittal sinus that also corresponds to CVT (Fig. F). Intravenous treatment of mannitol, subcutaneous injection of low-molecular-weight heparin calcium (5000 IU, two times/day) was initiated to reduce high intracranial pressure and to treat CVT. Cerebrospinal fluid (CSF) examination conducted on day 17 showed elevated protein levels at 1.87 (normal range: 0.15–0.45 g/L and immunoglobulin G levels at 267.0 (normal range: 0–34.0) mg/L. The CSF pressure was 210 (normal range: 80–180) mmH2O. Susceptibility-weighted imaging (SWI) obtained on the same day indicated bilateral hemosiderin deposition or hemorrhagic foci in the basal ganglia (Fig. ). Follow-up MRI obtained 25 days after admission showed symmetrical abnormal signals in the bilateral posterior limb of the internal capsule, putamen, external capsule, and insular lobe. The signals were hypointense on T1WI and hyperintense on T2WI, FLAIR, and ADC and were not limited by diffusion on DWI. Strip and dot-like signals, which were isointense and slightly hypointense on T1WI and hypointense on T2WI, can be observed in the lesions. DWI revealed bilateral hyperintensity on the frontal and occipital lobes (Fig. A1–E3). The flow signals of the superior sagittal sinus, straight sinus, and vein of Galen were significantly better on follow-up MRV (Fig. ). On the 28th day of admission, after the administration of gadolinium, MRI revealed abnormal enhancement within the bilateral basal ganglia, and the size of the lesions decreased on MRI conducted 25 days after admission (Fig. ). The patient was discharged with blurred vision on the 38th day. (Timeline of brain imaging was shown in Table ). |
pmc-6580590-1 | A 6-week-old Caucasian girl was admitted to a private hospital in South Africa with acute onset symptomatic cardiac failure secondary to anemia. Her parents reported a 1-day history of lethargy, poor feeding, shortness of breath, and irritability on a background history of progressive pallor.
There was no family history of note. Antenatal history included a low maternal pregnancy-associated plasma protein A (PAPP-A) level (0.376 IU/L) which resulted in a high-risk screening protocol for intrauterine growth restriction (IUGR) and fetal chromosomal anomalies. Cell-free fetal deoxyribonucleic acid testing from maternal blood excluded aneuploidies for the common trisomies [–] and subsequent fetal anomaly ultrasound and echocardiogram scans were all normal. A caesarean section was performed at 37 weeks for spontaneous labor, IUGR, and breech presentation. The delivery was uneventful and apart from a low birth weight of 2465 g, a healthy baby was discharged 3 days post caesarean section as per normal protocol.
On admission to hospital at 6 weeks of age, the baby under examination was severely anemic, tachycardic, and lethargic. There were no stigmata of immunocompromise, infection, or icterus. The baby weighed 3200 g with a head circumference of 38 cm.
There were no obvious craniofacial or skeletal abnormalities of note and examinations of her other systems were normal. The preliminary results with normal range for age in brackets showed a hemoglobin (Hb) level of 3.1 gm/dL (10–18 gm/dL) and a hematocrit of 9% (31–55%), mean corpuscular volume of 106 fl (85–123 fl), mean corpuscular Hb concentration 34 g/dL (32–37 g/dL), reticulocyte production index of 0.0, and an absolute reticulocyte count of 5.1 × 109/L (20–60 × 109/L). Her white cell count was low 4.0 × 109/L (5–19.5 × 109/L) but apart from a low neutrophil count of 0.32 × 109/L (1–9 × 109/L), the remaining differential count was normal. Her platelet count was increased 655 × 109/L (140–420 × 109/L). Her C-reactive protein was marginally raised at 7.7 mg/L (< 5 mg/L), and the infective work up was positive for Escherichia coli cultured from the urine. Tests for cytomegalovirus, human immunodeficiency virus (HIV), rubella, Epstein–Barr virus, toxoplasmosis, herpes simplex virus 1 and 2, and parvovirus B19 were all negative. A diagnosis of E. coli urosepsis was made. The baby was transfused with leukodepleted irradiated red cell concentrate to an Hb level of 10 g/dL and given goal-directed antibiotics and discharged 6 days later.
Readmission 14 days later with an anemia (Hb 7.7 g/dL) and associated reticulocytopenia of 7.0 × 109/L (20–60 × 109/L) prompted a provisional diagnosis of transient erythroblastopenia of childhood (TEC), which was made after infection, HIV, and tuberculosis were excluded. Three further admissions over the next 3 months for anemia requiring red cell transfusions and a persistent neutropenia prompted a bone marrow biopsy (Figs. and ).
Review of the bone marrow biopsy showed reactive features with markedly increased megakaryopoiesis and significant lymphocytic infiltrate. Flow cytometry demonstrated the infiltrate to consist of T cells, mature B cells, and hematogones. An absence of red cell precursors and immunohistochemical glycophorin stain on the bone marrow trephine confirmed a pure red cell aplasia.
Due to the unavailability of molecular and eADA testing in South Africa, specimens for molecular testing were sent to Oxford, UK, for identification of a possible heterozygous pathogenic variant in one of the genes associated with DBA. A multigene panel using the Multiplex Ligation-dependent Probe Amplification kit (MRC-Holland) confirmed a heterozygous whole gene deletion of RPL35A. In addition, dried plasma was sent to Duke University Medical Center, USA, to exclude adenosine deaminase 2 deficiency.
Once the diagnosis of DBA was made, the non-standardized management and limited experience in managing DBA in South Africa resulted in inconsistencies in opinion in the optimal early management of the case. Controversies around Hb transfusion threshold, optimal Hb target, frequency of transfusions, and timing and dosage of corticosteroid treatment and hematopoietic stem cell transplantation (HSCT) resulted in different opinions from different specialist practitioners.
Together with input from international DBA specialists managing large numbers of patients with DBA, the initial hematopoietic management in this case was directed toward correcting the anemia with transfusions every 3–5 weeks with irradiated leukodepleted RBC concentrate. A transfusion threshold of 8 g/dL was used and a volume of 10–15 ml/kg transfused on each visit. Planned iron chelation therapy to prevent transfusional hemosiderosis will be delayed until approximately 170–200 ml/kg of transfused red packed cells has been given. A planned trial of corticosteroids will be given at 1 year of age.
At follow-up at 6 months of age, the baby was stable requiring red cell concentrate infusion therapy every 3–4 weeks. Persistence in the neutropenia was noted, with no changes in the other cell lineages. Her current ferritin level is 573 μg/L and a total of 90 ml/kg of red packed cells has been transfused, thus, iron chelation therapy has not yet been instituted. Apart from a delay in gross motor development and growth (weight and height), all other parameters and development are within normal limits. |
pmc-6580602-1 | An asymptomatic 51-year-old woman without significant past medical history was diagnosed with HIV-1 infection on April 06, 2010 after her spouse died of HIV. Her baseline Chest X-ray was reported as normal and physical examination did not revealed any relevant clinical signs. She presented with a CD4+ T-cell count of 51 cells/μL and HIV viral load of 5.8 log10 copies/mL. ART was initiated with stavudine, lamivudine and nevirapine as per Indian National guidelines []. After 32 days on ART, she presented a clinical deterioration, with cough, afternoon fever, weight loss and night sweat, symptoms suggestive of pulmonary TB and subsequently confirmed to be drug-sensitive M. tuberculosis by sputum smear and culture (Fig. a). Standard ATT was started with Isoniazid, Rifampicin, Ethambutol, Pyrazinamide on May 08, 2010 (Fig. a) with nevirapine substituted for efavirenz. Repeat laboratory results revealed a CD4+ T-cell count of 146 cells/μL and viral load of < 2log10 copies/mL (400 copies/mL) (Fig. b). A panel of independent physicians reviewed the patient’s history, radiographs and physical examination. This independent panel of clinicians used the INSHI definition of unmasking TB IRIS [], composed by the following criteria: not receiving TB treatment at ART initiation; diagnosis of active TB after ART initiation; fulfilling WHO diagnostic criteria for TB; presentation within 3 months of ART initiation and heightened intensity of clinical manifestations once on TB treatment. The panel concluded that the patient had unmasking TB-IRIS at ART initiation.
After 48 days since ATT and efavirenz based ART were initiated, the patient presented with generalized pruritus and strong vague abdominal pain. Physical examination revealed fever, jaundice and left sided cervical lymphadenopathy. Laboratory tests were notable for high levels of total bilirubin 8.3 mg/dL (reference value [RV]: 0.2–1.0 mg/dL) with increases in aspartate aminotransferase AST, 72 U/L (RV: 5.0–40.0 U/L) and alanine aminotransferase ALT, 59 U/L (RV: 7.0–56.0 U/L). Abdominal ultrasound revealed enlargement and obstruction of the porta hepatis by periportal nodes with normal echotexture of the liver and gall bladder. At this crisis, ATT was modified to streptomycin, ofloxacin and ethambutol, second-line therapy (Fig. a), and ART was temporarily withheld, following advice from the panel of physicians reviewed, due to potential ART-induced liver toxicity. On July 19, 2010, with the liver function tests returning to normal (Table ), standard ATT regimen was re-introduced. After 11 days, ART was reinitiated as the HIV viral load was > 5.9log10copies/mL (Fig. b).
One week after ART reintroduction, the patient developed rapid clinical deterioration with focal complex partial convulsions prompting initiation of anticonvulsant therapy. Brain Computational Tomography (CT) scan revealed a frontoparietal space occupying lesion with peri-lesional, edema suggestive of tuberculoma (Fig. a). Following the CT scan results, cerebral spinal fluid was collected, and results excluded other potential opportunistic infections, such as neurocryptococcosis or toxoplasmosis. ART was again withheld temporarily while continuing ATT, because the independent clinical panel suggested the possibility of severe central nervous system (CNS) IRIS. Initially, she was treated with intravenous steroids and mannitol followed by acetazolamide to reduce perilesional edema. Oral prednisolone was gradually tapered over 8 weeks. Laboratory investigations demonstrated CD4+ T-cell count of 178cells/μL and HIV viral load of 2.83 log10 copies/mL. The patient recovered after 6 weeks, only to have a viral rebound (HIV viral load of 5.3 log10 copies/mL) (Fig. b). It was decided to reintroduce ART as an inpatient with stringent clinical monitoring while on oral steroids (Fig. a). In November 29, 2010, a repeat brain CT scan showed regression and calcification of the lesion. ATT was stopped on December 6, 2010 (total of 8-month duration) while ART and anticonvulsants were continued based on a consensus opinion from IRIS experts, TB experts and neurologists.
In May 2011, 5 months after completing ATT, the patient developed a swelling in the left iliac region. X-ray and CT of the spine were normal while ultrasonogram identified a localized intramuscular abscess which was drained under guidance, and the aspirate was negative for acid-fast bacilli (AFB) in smear and cultures for mycobacteria and gram positive or negative bacteria, as well as fungi. Laboratory tests results showed CD4+ T-cell count of 323 cells/μL and HIV viral load < 2 log10 copies/mL (Fig. b). Other laboratory exams were normal (Table ). Repeat CT scan of the brain showed further regression and calcification of the tuberculoma. Thereafter, the patient remained clinically asymptomatic and was followed for 30 months. Smears and cultures 30 months post ATT treatment were all negative after she converted in the first month and viral loads were suppressed as well. |
pmc-6580622-1 | A 66-year-old male with a smoking history of 30 pack-year and a drinking history of 60 g/d for 30 years visited our hospital following 1 month long coughing symptom with bloody sputum, and was diagnosed with stage IIIa (pT2N2M0) lung cancer on the left lower lobe (Fig. a). Thorocoscopic lobectomy was performed immediately to remove the left lower lobe of the lung and related lymph nodes. The excised tumor was confirmed as mixed invasive ADC and SC morphologically and immunohistochemically, accounting for 20 and 80% of the total tumor content, respectively (Fig. a).
We performed mutation profiling of the microdissected ADC and SC compartments of the surgical sample by targeting 416 cancer-relevant genes (GeneseeqOne, Nanjing Geneseeq Technology Inc., China) using hybrid capture-based targeted next-generation sequencing (NGS) on a HiSeq4000 platform (Illumina) []. As depicted in Table , we observed alterations of multiple oncogenes and tumor suppressor genes that were shared between the two compartments, including EGFR, NF1, SMARCA4, and TP53 mutations, as well as MET gene amplification, consistent with the prior findings that SC has a high mutation rate with the predilection for co-occurrence of more than one driver mutations [, ]. This may account for the high malignancy and aggressive behavior of SC and its poor response to either traditional chemotherapy or radiotherapy as seen in this patient. A rare TP53 deletion (c.97_133 deletion) was detected in both ADC and SC tissues. This variation may result in TP53 exon 4 mis-splicing, which is more frequently seen in sarcoma []. Interestingly, an additional TP53 mutation 97-2A > T that is located right on the splicing accepter of exon 4 was only identified in SC tissue indicating a potential impact of this alteration in SC development, as well as a unique synonymous AXIN2 mutation (Table ). These data suggested a linear evolution model of SC progression from the ADC compartment in the primary tumor of this patient.
About 4 weeks after surgery, adjuvant chemotherapy (carboplatin 0.15 D1–3 + pemetrexed 0.8 D1) was administrated to the patient. However, the patient was diagnosed with cancer relapse within a month. CT scan revealed that soft tissue masses progressively increased in the anterior mediastinum, which was further confirmed as SC by biopsy (Fig. b). Genetic characteristics of the recurrent SC was also performed using targeted NGS. Aside from the alterations seen in primary SC tumor tissue, the relapsed SC acquired a novel PHF20-NTRK1 fusion where PHF20 intron 2 fused to the intron 4 of NTRK1 at a high variant allele frequency (VAF) (Table and Fig. a), resulting in a PHF20-exon 2: NTRK1-exon 5 fusion mRNA with potential in-frame translation (as depicted in Fig. b). The resultant fusion protein preserves the whole TRKA kinase domain of NTRK1, and therefore may constitutively activate NTRK1 and contribute to the oncogenesis of the relapsed SC. We further validated the presence of this gene fusion at DNA level in the recurrent SC by PCR amplification of the fusion region followed by Sanger sequencing for sequence confirmation (Fig. c). Due to the presence of multiple driver gene alterations, and the unavailability of NTRK1 inhibitor, the patient then received mediastinal tumor palliative radiotherapy (DT = 18Gy/9F), but responded poorly to the treatment and deceased 16 weeks post-operation (Fig. b). |
pmc-6580630-1 | A 68-year-old man with a history of smoking and hypertension was admitted to our hospital for right-sided weakness and aphasia. On admission, his blood pressure was 170/108 mmHg. Neurologic examination showed right hemiplegia, facial paralysis and aphasia. Brain computed tomography (CT) showed a right parietal cSAH (Fig. a). Moreover, results from magnetic resonance imaging (MRI) T2-weighted fluid-attenuated inversion recovery were compatible with cSAH, which was localized to the sulcus in the right parietal lobe (Fig. b), Diffusion-weighted imaging was performed and showed hyperintense lesions in the distribution of the left middle cerebral artery (Fig. c). Further evaluation with CT-angiography showed occlusion of the left ICA and compensatory flow from the right ICA via the anterior communicating artery (Fig. d and e). Laboratory tests, including evaluations for inflammation, coagulation parameters, autoantibodies and neoplastic markers, were all unremarkable. Cerebral amyloid angiopathy (CAA) was excluded because of the absence of microbleeds on susceptibility-weighted imaging. There was no evidence of posterior reversible encephalopathy syndrome, without typical parieto-occipital vasogenic edema on MRI. Moreover, color Doppler ultrasonography showed atherosclerotic plaque formation in the bilateral carotids and lower extremities. Thus, the diagnosis of large artery atherosclerosis stroke was confirmed and full anti-atherosclerosis therapy was initiated (aspirin and atorvastatin). At 3 months’ follow-up, the patient had residual right-side limbs weakness and mild disability (modified Rankin Scale 2). |
pmc-6580630-2 | A 56-year-old woman with a history of untreated rheumatic heart disease for 20 years developed left-sided weakness associated with headache for 2 days. There was no history of hypertension, diabetes or hyperlipidemia. Her blood pressure at presentation was 91/58 mmHg. On neurological examination, she was somnolent with a binocular gaze to the right side. Her left limb muscle strength was grade 0/5 with hyperreflexia and positive pathological signs after hospitalization. CT revealed a left parietal cSAH (Fig. a). MRI with diffusion-weighted imaging confirmed the diagnosis of acute right cerebral hemisphere infarction and left parietal cSAH (Fig. b and c), without signs of microbleeds on susceptibility-weighted imaging. Digital subtraction angiography performed the next day showed right ICA occlusion (Fig. d and e). Laboratory findings revealed no evidence of vasculitis, infections, and coagulation disorders. Transthoracic echocardiography showed rheumatic heart disease with severe aortic stenosis and decreased left ventricular diastolic function. The ischemia was classified as ICA occlusion due to cardioembolic stroke. Warfarin was initiated after 2 weeks. Three months later, she underwent elective aortic valve replacement and continued long-term warfarin therapy. She could self-care after a follow-up period of 6 months and had modified Rankin Scale of 2. |
pmc-6580698-1 | An 81-year-old Caucasian female, healthy weight (44 kg, or 97 pounds), without
systemic diseases, presented herself in a tertiary hospital ambulatory with a
complaint of bulge and pain in the right groin for 10months. The pain was mild and
usually appeared when she performed physical effort. No further symptoms were
recorded. The patient had no episode of acute cholecystitis previously. She had
urinary incontinence surgery 12 years ago and a Lichtenstein hernioplasty on the
left side 10 years ago with no signs of recurrence. She had a descending thoracic
aortic aneurysm measuring 7.1×6.3 cm on its major axial diameter and an
infrarenal abdominal aortic aneurysm measuring 6.4×6.1 cm on its axial
diameter and was planning to undergo an endovascular repair in two steps. She also
had a cystocele. The physical exam showed a bulge on the right inguinal region with
no expansion on coughing. The palpation showed a hard bulge and the hernia was not
reducible with pain on manipulation (). |
pmc-6580780-1 | A 48-year-old right-handed man, who worked as a fireman, presented with a 2-year history of difficulty climbing the stairs and ‘slapping’ feet. In addition, he reported a 10-year history of low back pain associated with a burning sensation of the feet. Bladder and bowel function was normal. On examination, he had bilaterally large calves and proximal lower limb muscle weakness. There was mild weakness of hip flexion (MRC grade 4/5), moderate weakness of knee extension (MRC grade 3/5) and severe weakness of ankle dorsiflexion (MRC grade 2/5). The upper limb examination was normal. At the time of presentation there were no signs of spasticity and all reflexes were present. The sensory examination was normal.
He had an elevated serum creatine kinase (CK) concentration at 1200 IU/L. Nerve conduction studies showed normal compound muscle and sensory action potentials. Electromyography (EMG) showed evidence of chronic denervation and reinnervation in tibialis anterior and rectus femoris muscles (see ). A quadriceps muscle biopsy showed fibre-type grouping and changes most in keeping with neurogenic atrophy. His monozygotic twin was examined and was found to be normal (clinically, radiologically and biochemically).
An MR scan of the whole spine showed a significant disc protrusion at T11/12 resulting in spinal cord compression with associated intramedullary signal change (see ). An MR scan of the lower limb muscles showed fatty infiltration (a sign of either a primary myopathy or denervation) in the quadriceps, adductors and tibialis anterior but sparing the hamstrings, that is, predominantly L2, L3, L4 and L5 innervated muscles (see ).
The patient continued to progress such that he was only able to walk 50 m unassisted. Following decompression of the T11/12 disc, his exercise tolerance improved and he has since returned to work and can walk unlimited distances. Following surgery he has developed ankle clonus and extensor plantar responses, clinical signs that were absent before surgery. His serum CK concentration has returned to normal. |
pmc-6580780-2 | A 48-year-old man of Caribbean descent presented with a 4-year history of slowly progressive bilateral foot drop progressing to proximal lower limb weakness. His upper limbs were normal and there were no sensory symptoms. More recently he had developed urgency of micturition. His medical history was significant for diabetes and hypertension.
On examination, there was distal muscle wasting of the legs with bilateral foot drop. There were fasciculations in both quadriceps with symmetrical proximal weakness (hip flexion MRC grade 4/5, hip extension 4/5, knee flexion 3/5, knee extension 4/5) and severe distal weakness (ankle dorsiflexion MRC grade 1/5, ankle plantar flexion 2/5). Reflexes were absent in the lower limbs. Joint position sense was impaired up to the ankle and pinprick sensation was reduced up to the knee. The upper limbs were unaffected.
His serum CK concentration was elevated, ranging from 800 to 1000 IU/L. Nerve conduction study showed absent compound muscle action potentials to extensor digitorum brevis and abductor hallucis and normal sensory action potentials (see ). Needle EMG showed acute and chronic denervation changes in iliopsoas, vastus medialis, tibialis anterior and medial gastrocnemius muscles (see ). A quadriceps muscle biopsy revealed neurogenic changes. An MR scan of spine showed bilateral facet joint hypertrophy and ligamentum flavum hypertrophy with resultant spinal canal stenosis at T11/12 and corresponding intramedullary signal change (see ). The rate of clinical progression has been slow and he has not undergone decompressive surgery. |
pmc-6580786-1 | A 25-year-old male personal trainer ran a ‘fun run’ on a hot day wearing a heavy costume. He collapsed 9 km into the run and was brought to hospital. He was agitated and confused (Glasgow Coma Scale score 10; E3, V3, M4), feverish (40.5°C) and tachycardic (149 bpm) with muscle pain and weakness. He was cooled and given intravenous fluids. Investigations showed serum creatine kinase (CK) concentration was 3000 IU/L, rising to 105 000 IU/L at 24 hours, with an acute kidney injury and myoglobinuria. He was discharged 3 days later with no neurological deficit and normal renal function; his CK normalised after 3 weeks. He was an athletic man who had completed several marathons, with no medical conditions or family history of neuromuscular disease. |
pmc-6580786-2 | A 42-year-old male security supervisor attended a training course involving intense physical exertion. He became dehydrated and took oral and topical ibuprofen. He attended the emergency department 3 days afterwards with flank pain and dark urine. Neurological examination was normal but his serum CK was >300 000 IU/L and he required dialysis for acute kidney injury with myoglobinuria. He was discharged after 1 week with improving kidney function and CK 2750 IU/L. Repeat blood tests after 3 months showed normal kidney function and CK 334 IU/L, remaining elevated at 550 IU/L at 1 year. He had developed exercise intolerance in his teenage years without seeking medical attention. Further inquiries revealed his sister, with whom he had little contact for many years, had been diagnosed with McArdle’s disease in childhood. Subsequent gene testing demonstrated he was homozygous for the c.148C>T (p.Arg50Ter) pathogenic mutation in myophosphorylase (PGYM). |
pmc-6580995-1 | A 29-year-old male with 18 months of intermittent fevers, night sweats, and 6 kg weight loss presented to outpatient cardiology. He had a history of Tetralogy of Fallot with multiple cardiac surgeries, including Blalock shunt placement at age 7 days followed by repair at 3 years of age, homograft pulmonary valve replacement (PVR) in 2006, and bioprosthetic PVR in 2014. Other relevant history included travel to Pakistan, Thailand, Laos, and Myanmar after PVR in 2014, use of a LivaNova 3T Heater-Cooler device during PVR surgery in 2014, and consumption of unpasteurized milk in the Midwestern United States. He denied animal contact.
Vital signs were normal. Physical examination was notable for a holosystolic murmur and hepatosplenomegaly. Initial blood cultures and a fourth-generation HIV screening test were negative. Transesophageal echocardiography demonstrated severely elevated pulmonary artery (PA) pressure and an erratically moving echodensity on the pulmonary valve suggestive of vegetation. The patient was subsequently admitted to the hospital for further management of presumed CNE.
Initial concerns included Mycobacterium chimaera prosthetic valve endocarditis given a documented outbreak associated with contaminated LivaNova 3T Heater-Cooler devices []. Furthermore, the patient brought a letter from the hospital where the PVR was performed in 2014 warning of possible exposure to M. chimaera. Other potential etiologies included Bartonella henselae, Brucella species, and C. burnetii.
Although the patient was clinically stable, his cardiologist had concern for decompensation and sudden cardiac death due to severely elevated PA pressure. To prevent reinfection of new prosthetic material, the cardiologist consulted the infectious diseases service for empiric treatment recommendations before surgery. Upon our recommendation, serologic tests for B. henselae, Brucella species, C. burnetii, and Legionella pneumophila, as well as acid-fast bacilli blood cultures were sent. However, empiric therapy for the multiple etiologic agents under consideration, including M. chimaera, was not recommended given that it could reduce diagnostic yield from cardiac tissue culture and commit the patient to long-term empiric therapy with toxic antimicrobials (eg, amikacin). Based on advice from a physician with M. chimaera expertise, we sent the patient’s plasma for NGS of mcfDNA to facilitate rapid and comprehensive diagnosis including evaluation for M. chimaera infection () []. |
pmc-6581023-1 | A 52-year-old Thai female was diagnosed with stage 4 lung adenocarcinoma with adrenal metastases, T4N3M1b. Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutation analyses were negative. Programmed death-ligand 1 (PD-L1) expression on tumor cells was more than 1%. She received 1,200 mg of atezolizumab every 3 weeks for 5 cycles. She achieved a partial response by 12 weeks after therapy, then the medication was discontinued after 18 weeks of treatment due to disease progression. She had no other underlying diseases and no family history of diabetes and other autoimmune disease. Her fasting plasma glucose was 85 mg/dL (4.7 mmol/L) before atezolizumab initiation (plasma glucose levels during therapy are shown in ). She presented with diabetic ketoacidosis (DKA) at 24 weeks after the first dose and 9 weeks after cessation of atezolizumab. She was first diagnosed with diabetes with an A1c of 7.9% (63 mmol/mol) and was discharged from primary care hospital with glipizide. Three days after discharge, she was admitted to our hospital with severe DKA. Her initial serum glucose was 332 mg/dL (18.4 mmol/L) and A1c was 7.9%. She had wide gap metabolic acidosis with serum bicarbonate of 9.9 mEq/L, anion gap of 24.1, and the arterial pH of 6.9. Her serum β-hydroxybutyrate was 5.91 mmol/L, and lactate was 1.06 mmol/L. There was no infection, thromboembolic event, or medication causing hyperglycemia. Atezolizumab-induced autoimmune diabetes was suspected. At 7 weeks after DKA, fasting C-peptide was <0.03 nmol/L (0.1 ng/ml) and fasting insulin level was <1 μIU/ml while plasma glucose was 380 mg/dL (21.1 mmol/L). Anti-glutamic acid decarboxylase 65 (GADA) and anti-tyrosine phosphatase-like insulinoma antigen 2 (anti-IA2), measured by enzyme-linked immunosorbent assay (ELISA) method, were positive (7.2 U/ml; >5 U/ml) and negative (<7.5 U/ml), respectively. We did not test for anti-Zinc transporter isoform 8 (ZnT8) and anti-insulin (IAA) since the tests were unavailable in our country. The results of HLA class II typing by sequence-specific oligonucleotide primed PCR were DRB1*03, DRB1*14, DQB1*02, and DQB1*05 (DR3-DQ2/DR14-DQ5). She was being treated with basal-bolus insulin therapy, consisted of once-daily basal insulin glargine (Lantus®) plus thrice-daily prandial insulin aspart (Novorapid®), with a total daily insulin dose of 0.5 units per kilogram per day. Her thyroid function tests, both before and after receiving atezolizumab, and the levels of other anterior pituitary hormones after receiving atezolizumab were normal, as shown in . She had other adverse immune-associated reactions during the first cycle of therapy, including neuralgia grade 1 and transaminitis grade1, which resolved spontaneously after 3 weeks. Her lung cancer was then treated with paclitaxel and carboplatin leading to partial remission. |
pmc-6581326-1 | A 76-year-old active and independent woman with a history of diabetes mellitus, hypertension and chronic cervical and lumbar degenerative disease presented to our hospital with a three-day history of headache and minimally altered mental state (AMS, rude and aggressive per family). She was afebrile on presentation and initial laboratory and radiological workup was negative for urinary tract infection (UTI) or pneumonia, but did reveal white blood cell count (WBC) of 11.100/µl. She was observed without antibiotic therapy for two days. In the morning of the day three of admission she had WBC of 7.200/µl with 15% bands and was still afebrile. On physical exam three hours afterwards, she was completely disoriented with Glasgow Coma Scale score of nine (E2M5V2) and significant photophobia, was febrile to 103.2F but otherwise hemodynamically stable. Kernig’s and Brudzinski’s signs were equivocal. Computed tomography (CT) and magnetic resonance imaging (MRI) head, urinalysis, and chest X-ray showed no acute pathology. Image-guided lumbar puncture was unsuccessful due to diffuse structural spine changes. Intravenous ceftriaxone, vancomycin, ampicillin, acyclovir and dexamethasone were started for empiric meningitis treatment. Urine antigen and blood cultures results were positive for Streptococcus pneumoniae and antibiotic therapy was narrowed down to ceftriaxone on day three. A repeat chest X-ray revealed a new consolidation visualized at the right lung base, consistent with pneumonia. Even though fever resolved and leukocytosis improved, due to minimal mental status improvement, and based on the S. pneumoniae sensitivity from blood cultures, rifampicin was added to therapy from days 10 to 20 which correlated with limited but gradual clinical improvement. On day 17, follow-up MRI brain showed multiple new foci of restricted diffusion in the frontal and parietal lobes, consistent with septic emboli. Transthoracic echocardiogram revealed a new mobile mass on the aortic valve consistent with infectious endocarditis, confirming the diagnosis of Austrian syndrome. During hospitalization, the patient also developed septic knee arthritis, C1 spine subluxation, monoclonal gammopathy, and acute hypoxic respiratory failure requiring a short period of intubation. Ceftriaxone therapy was continued, and the patient’s mental status improved. She was discharged on day 31 and completed a total of six weeks of ceftriaxone treatment. One month later, she was admitted for AMS and UTI, treated with antibiotics with mental status improvement. One month after that, she returned with AMS, muscle twitching, and UTI, and was found to have a right frontal focal status epilepticus. MRI and CT head ruled out new infectious or inflammatory lesions. The patient was discharged to home hospice where she eventually died. |
pmc-6581329-1 | Our patient, a 27-year-old male with a significant medical history of tobacco use and a positive family history of CVD (father had fatal MI at 38 years of age), had presented in 2016 with shortness of breath (SOB) and acute retrosternal chest pain. His electrocardiography (ECG) showed ST-elevation myocardial infarction (STEMI) with ST elevations in leads V1-V4 and ST depressions in the reciprocal leads. Echocardiogram (echo) showed severe left ventricular dysfunction (LVD), akinetic left ventricular (LV) apex, and an ejection fraction (EF) of 25%. Cardiac catheterization revealed thrombotic occlusion of the left anterior descending (LAD) artery (Figure ) in which percutaneous coronary intervention (PCI) with stent placement was performed as part of immediate management for anterior wall myocardial infarction (AWMI). Deficiency of protein C and protein S was diagnosed through coagulation profile; values seen were 35% and 56%, respectively, as shown in Table .
Lipid profile was found to be normal. After adequate management, he was discharged on aspirin, clopidogrel, rosuvastatin, and loop diuretic. After one year our patient, found to be noncompliant to medications, was admitted again with the complaint of SOB, fever, and generalized edema for which he was managed as a case of ischemic heart disease (IHD). Echo then showed declining EF of 20% with prominent DCM. Computed tomography (CT) scan of the chest and abdomen revealed loculated pleural effusion, dilated pulmonary vessels, and gross ascites in the presence of cor pulmonale.
Now, the patient arrived in emergency room (ER) on February 28th, 2019 with severe dyspnea, pedal edema, cellulitis of left leg up to the knee, and fever. Pedal edema was bilateral without periorbital swelling whereas the SOB of New York Heart Association (NYHA) class III along with orthopnea was accompanied with white productive cough. A complaint of bilateral blurred vision for the past one week was also noted.
Physical examination showed an anemic, jaundiced and mildly icteric young male, with a blood pressure (BP) of 110/80 mmHg, respiratory rate (RR) of 22 breaths/min, temperature of 100 degree Farenheit with raised jugular venous pressure (JVP) and engorged veins. Fine rising crepitations were auscultated in lower and mid zones of chest with a pansystolic murmur all over the precordium. Abdomen was mildly tender with palpable liver, whereas the central nervous system (CNS) was grossly intact.
Lab evaluation on admission revealed hemoglobin (Hb) of 12.5 g/dl [Normal (N) = 13.8-17.2], total leukocyte count (TLC) of 17.8 x 109/L (N = 4-11), high C-reactive protein (CRP) value of 119.4 mg/dL (N = 1.0-3.0), and prothrombin time (PT) of 12.4 s (N = 11-13.5). Electrolytes were normal except sodium (Na) which was decreased up to 116 mEq/L (N = 135-145). Total bilirubin was raised up to 5.14 mg/dL (N = 0.3-1), however, albumin and globulin levels were within the normal range. Chest X-ray (CXR) showed diffuse pulmonary edema with prominent DCM (Figure ). The patient was initially managed with digoxin, ascard, atorvastatin, levofloxacin, augmentin, and loop diuretic.
His echo demonstrated a decreased EF of 15% with severe tricuspid regurgitation (TR) and LVD. In addition to the findings of previous echo report, akinesia was also noticed in the interventricular septum (IVS) and anterior and inferior walls along with moderate pericardial effusion. Abdominal ultrasound (U/S) revealed hepatomegaly measuring 18.4 cm. Inferior vena cava (IVC) and hepatic veins were found dilated in the Doppler U/S of hepatic and portal veins whereas that of lower limb vessels showed internal echoes in the right popliteal vein representing sluggish flow. No evidence of stenosis and deep vein thrombosis (DVT) was observed.
Although the patient recovered from cellulitis and pedal edema, there was a progressive declination in his EF which dropped up to 10% along with the worsening DCM (Figure ).
The BP also dropped up to 60/30 mmHg. Therefore, a worse prognosis of our patient was established and he was discharged with diuretics, beta blockers, nitrates, and anticoagulants. Angiotensin converting enzyme (ACE) inhibitors were avoided due to decreased BP. |
pmc-6581386-1 | A 13-year-old female without a significant previous medical history presented unresponsive to a level I trauma center. The patient was fully vaccinated with the exception of the seasonal flu vaccine. Per the parent’s report, the patient had experienced cough and cold symptoms for two weeks. Thirty minutes following the patient’s departure to bed, she was heard screaming. Upon responding to the patient’s cry, her parents discovered her minimally responsive and having vomited. With significant assistance, she was able to walk to their car. Upon arrival at the emergency department, the patient was completely non-responsive.
Initial vitals were a temperature of 35.2 degrees Celsius, pulse 70, blood pressure 117/65, respiratory rate 12, and saturation 100% on room air. Upon examination, the patient was Glasgow Coma Scale (GCS) three, breathing spontaneously and with a bounding pulse. Pinpoint pupils and a disconjugate gaze were noted. Intravenous naloxone 0.4 milligrams (mg) was administered without a change in mental status, and a subsequent 1 mg dose resulted in no further improvement. Non-contrasted computed tomography (CT) was read as suggestive of a small perimesencephalic bleed, but nothing that should be causing her symptoms.
Laboratory studies revealed leukocytosis (white blood cell count of 15.5 x 10^3/microliter). In conjunction with the patient’s hypothermia, antibiotics were initiated empirically (systemic inflammatory response syndrome present; sepsis presumed with the most likely etiology being meningitis). An acetaminophen level of 138 micrograms/millilitre was identified. Acetylcysteine was initiated to address a possible chronic acetaminophen toxicity (the assumption being that she had been chronically treating her symptoms with acetaminophen). A lumbar puncture (LP) was obtained, and a meningitis encephalitis polymerase chain reaction (PCR) study ordered. Initial cerebral spinal fluid results (glucose 85/100milliliter, protein 31/100milliliter, and cell count Ω of three red blood cells and one polymorphonuclear neutrophil) were all within normal limits. The decision was made to intubate the patient as her mental status was not improving and she had begun to vomit again. The patient was then admitted to the pediatric intensive care unit with influenza A and B PCR pending. Shortly after her arrival at the pediatric intensive care unit (PICU), the influenza A PCR resulted positive.
The patient’s inpatient course included a magnetic resonance angiogram (MRA) of the brain and electroencephalogram (EEG). The MRA was unremarkable. This study, in combination with LP results non-suggestive of a subarachnoid hemorrhage, suggested that the earlier concern for a perimesencephalic bleed was a false positive. Her EEG revealed “intermittent generalized slowing consistent with toxic metabolic encephalopathy.” Flu encephalopathy was determined to be the etiology of the patient’s altered mental status. Incidentally, further laboratory studies showed that the patient was infected with the H3 influenza A variant which was previously associated with an increased incidence of flu encephalopathy in Japan in the 1990s [].
After 72 hours in the PICU on intravenous peramivir, the patient’s mental status improved significantly; she was extubated, and in the days following, had a complete neurologic recovery. Her normal magnetic resonance imaging (MRI) and her subsequent full recovery are consistent with the prior finding, in adult patients, that a normal MRI is of prognostic value []. |
pmc-6581387-1 | A 14-year-old male patient presented to the outpatient clinic with dizziness since the previous day without any history of loss of consciousness, weakness in the extremities or seizure episode. He also complained of non-bloody, nonbilious, and projectile vomiting with a negative history of abdominal pain and diarrhea. In the past, he had identical complaints of dizziness one and half months back after falling off his bicycle. His parents had a nonconsanguineous marriage. There was a positive family history with his father suffering premature cardiovascular death at the age of 35 years.
On presentation to the clinic, he was in a hemodynamically stable state. Neurological evaluation was normal without any complaints of weakness, positive Babinski sign, or sensory involvement. He was admitted on the floor for thorough evaluation for his vertigo. Local causes of vertigo were ruled out on initial evaluation by an ear, nose, and throat consultation. Ophthalmology evaluation was done to rule out causes of raised intracranial tension, which showed no evidence of papilloedema on indirect ophthalmoscopy. The patient was reviewed anthropometrically which showed an increased arm length more than height.
The patient suddenly became drowsy along with complaints of right-sided weakness and continuous hiccups with high fever spikes, thus he was shifted to pediatric intensive care unit and his neurological assessment showed upper motor neuron facial nerve palsy as evident from right-sided hemiparesis.
The magnetic resonance imaging showed bilateral cerebellar non-hemorrhagic infarcts. Later, the patient deteriorated and developed respiratory distress along with pooling of secretions, hoarseness of voice, and deviation of uvula to the right side with an absent gag reflex, thus, suggesting a medullary component with ninth and tenth nerve involvement.
Other examinations including complete blood count, coagulation profile, 2D (transthoracic) echocardiogram, and electrocardiogram were found to be normal and helped us to rule out arrhythmias for syncope workup. The antinuclear antibody assessment was negative and helped to rule out any autoimmune disorder. Magnetic resonance angiography showed a vascular loop of the anterior inferior cerebellar artery around the seventh cranial nerve on the right side. Furthermore, he had elevated homocysteine levels (18.54 micromoles/liter). Thus, he was diagnosed with acute non-hemorrhagic bilateral cerebellar and medullary infarction with homocysteinemia after a careful assessment and exclusion of all relevant differential diagnoses.
The patient was given supportive treatment while admitted to the pediatric intensive care unit. He was treated by oral antispasmodics for spasms and anti-emetics for vomiting. For homocysteinemia, he was managed with oral pyridoxine, folic acid, and aspirin. On follow-up visits, the patient was doing well. |
pmc-6581388-1 | A 56-year-old woman underwent an uncomplicated left shoulder bone spur removal under general anesthesia with 2 mg of versed, 100 mcg of fentanyl, 150 mg of propofol, and sevoflurane in an outpatient surgery center. After completion of the procedure, the anesthesiologist performed an interscalene nerve block for post-operative pain control utilizing 30 mL of bupivacaine (0.25%). Approximately 5 min after completion of the block, the patient developed bilateral mydriasis, paralysis of all extremities, and respiratory arrest. The patient was immediately intubated, administered IV fluids, ephedrine 15 mg IV, and transferred to an emergency department (ED).
On ED arrival the patient was being ventilated through an oral endotracheal tube and was completely paralyzed. Her vital signs were: blood pressure (BP) 108/56 mmHg; pulse 86 per minute; respiratory rate 24 breaths per minute on a ventilator. Her pupils were 6 mm and unresponsive to light bilaterally. She had no response to painful stimulation and had no spontaneous respirations on a ventilator. Her initial blood tests included a complete blood count, electrolytes, liver function tests, cardiac enzymes, and coagulation tests. The lab results were all unremarkable except for a phosphorus of 1.7 mg/dL and lactate of 4 mmol/L. In the ED she was administered a 1-L normal saline bolus and 20% intravenous lipid emulsion 85 mg. Over the next 4 h, the patient progressively regained motor and sensory functions followed by successful extubation in the ED. She was admitted to the hospital for observation and discharged home the next day without any neurologic sequelae. |
pmc-6581410-1 | A 57-year-old male was evaluated in the emergency department for lightheadedness. Approximately 12 hours prior to presentation, he intentionally ingested 30 tablets of amlodipine 10 mg with suicidal intent, and afterwards he took a nap. When he woke up, he was unable to move his legs and felt lightheaded. He had been on amlodipine for three years as a treatment for hypertension. His past medical history was significant for chronic alcoholism and human immunodeficiency virus (HIV) apart from hypertension. On arrival, the patient was alert but reported feeling weakness all throughout his body and lightheadedness. On examination, he was found to be bradycardic with a heart rate of 50 beats per minute and he had hypotension with a systolic blood pressure of 70 mm Hg. He was administered 2 liters of intravenous 0.9% saline. His laboratory investigation was remarkable for potassium of 3.2 mmol/L (reference range 3.5-5.1), bicarbonate of 19 mmol/L (reference range 22-30), creatinine of 5.3 mg/DL (reference range 0.82-1.5), and calcium of 8.2 mg/DL (reference range 8.3 to 10.1).
The patient was administered two more liters of 0.9% normal saline as a bolus, and after consultation with the regional Poison Control Center, a recommendation to administer 20 grams of calcium gluconate in dextrose solution was made. The initial QTC on electrocardiogram (EKG) was 525 (Figure ). The initial EKG showed normal sinus rhythm with prolonged QT interval with U waves. The patient was admitted to the medical intensive care unit (ICU) for further treatment.
Intravenous infusion of calcium chloride 20 grams in dextrose 5% was administered at the rate of 100 ml/hour. Basic metabolic profile (BMP) drawn prior to the calcium chloride infusion showed potassium 2.7 mmol/L, bicarbonate 17 mmol/L, creatinine 4.7 mg/DL, and calcium 9.3 mg/DL. Approximately six hours after the infusion of calcium chloride was started, the BMP was checked and showed potassium of 3.6 mmol/L as it was supplemented, bicarbonate of 18 mmol/L, creatinine of 2.7 mg/DL, and calcium of 22.7 mg/DL. At that point, the calcium chloride infusion was stopped. EKG at that time showed QTC 393 ms (Figure ). The serum calcium level was checked five hours later and showed calcium of 19.4 mg/DL. His urine output over the last five hours was 400 to 425 ml an hour. Three hours later, the patient started complaining of severe central abdominal pain. A computer tomography (CT) scan of the abdomen without contrast was obtained and showed significant peripancreatic stranding extending within the anterior pararenal space and tracking down along the right psoas muscle and left psoas muscle into the pelvis. These signs were consistent with acute pancreatitis (Figure ). Treatment was started with intravenous isotonic solution, and this improved his blood pressure and pain management was achieved with as-needed opiate. Twenty-four hours after arrival into the hospital, his potassium was 4.0 mmol/L, creatinine was 1.3 mg/DL, and calcium was 11.3 mg/DL.
The patient's clinical course gradually improved and he no longer required ICU monitoring and was transferred to the floor. Inpatient psychiatry consultation was placed and he was recommended for admission to the Behavioral Science unit. On the day of discharge, his potassium level was 4.0 mmol/L, creatinine was 1.0 mg/DL, and calcium was 9.5 mg/DL. |
pmc-6581412-1 | We present the case of an 18-year-old male high-school senior who presented to the emergency department (ED) for complaints of productive cough with associated dyspnea for 10 days. He was seen the day previous at an urgent care center where he received a chest X-ray (CXR) and was discharged with azithromycin for presumed pneumonia. He was given a call back the following day for referral to the ED because the CXR was read as pneumomediastinum.
In the ED, the patient’s triage vital signs included a blood pressure of 148/89, heart rate of 72 beats per minute, respiratory rate of 20 breaths per minute, oxygen saturation of 92% on room air, and a temperature of 99.6 Fahrenheit orally. The patient was an otherwise physically active and healthy male with a medical history of childhood epilepsy and seasonal allergic rhinitis. He noted that roughly 10 days ago, he began developing a dry cough, which progressed to include scant green sputum production. He had dyspnea, dysphagia, sore throat, intermittent wheezing, and positive sick contacts, especially through his participation in team sporting events. He participated in weight lifting, basketball, and lacrosse at a relatively high level. He noted that about three weeks ago, he took a “big hit” to the chest during a game of lacrosse but denied any symptomatology at that time. He did not associate his current symptoms to any traumatic event. Otherwise, his sporting regiment included significant physical exertion and vocal exertion but denied any extranormal periods of physical or vocal exertion outside of his typical regimen. No further history of recent physical traumatic events was noted. He denied any history of use of cigarette, cigar, marijuana, or illicit substances, including cocaine. He denied any complaints of headaches, dizziness, chest pain, palpitations at the time of evaluation. A CXR and computed tomography (CT) of the chest without contrast was obtained with findings of subcutaneous air in the thorax and around his neck (Figures -). This confirmed that the patient had pneumo-mediastinum. On physical exam, he was 73 inches (185 cm) tall and weighed 175 lbs (79 kg). The patient was noted to have bilateral basilar minimal end expiratory wheezing without crackles or rhonchi. Palpable subcutaneous emphysema in the supraclavicular region and neck was present. There was no jugular venous distension, abnormal heart sounds, or lower extremity edema.
The patient was subsequently admitted for observation of dyspnea. His initial bloodwork was significant for leukocytosis with a white blood cell (WBC) count of 15 700 (normal, 3400 to 9600 cells/mcL). The patient was treated with 100% oxygen and albuterol-ipratropium nebulizer treatments and obtained re-imaging of his chest with a CXR. Re-imaging of his chest revealed stable air tracking through his mediastinum. The patient’s initial complaints of dysphagia had improved during his hospital stay and he was able to tolerate oral intake without any nausea or vomiting. The patient’s leukocytosis resolved within 24 hours and his symptomatology of cough and dyspnea had improved. The patient was subsequently discharged with outpatient pulmonology follow-up. The patient’s overall length of stay was 46 hours.
On outpatient follow-up, repeat CT of his chest four weeks thereafter demonstrated complete resolution of free air in the mediastinum. The patient had no other complaints. He was able to participate in a light exercise program and was to continue routine follow-up with his primary care physician. |
pmc-6581413-1 | We report the case of a 58-year-old female with history of type 2 diabetes mellitus who was admitted to the medical intensive care unit for altered mental status. Her past medical history was relevant for hydrocephalus requiring ventriculoperitoneal (VP) shunting 25 years ago, essential hypertension and obstructive sleep apnea. The patient was last seen at her baseline mental status three hours prior to presentation. Upon arrival, her primary survey was remarkable for a Glasgow Coma Scale score of 6. No focal neurologic deficits were appreciated. The patient was subsequently intubated for airway protection due to minimal responsiveness. Extensive laboratory workup including complete blood count (CBC), chemistries, urinalysis and illicit drug screen was unrevealing. Magnetic resonance imaging of the brain (Figure ) showed hydrocephalus involving the lateral and third ventricles with associated trans-ependymal flow of the cerebrospinal fluid (CSF) suggestive of shunt malfunction.
CSF analysis was negative for infection. An electroencephalogram showed non-specific mild right temporal slowing and moderate generalized slowing. A VP shunt exchange was performed on day 2 of the hospitalization after obstruction was confirmed. Nevertheless, the patient’s clinical status worsened and severe metabolic acidosis was noted the following morning (Table ). Workup was remarkable for a high anion gap (>28 mEq/L), normal lactic acid and elevated serum beta-hydroxybutyrate level (10.09 mmol/L). Arterial pH was 7.20. Blood sugars ranged between 130 and 150 mg/dL. Urinalysis was positive for glycosuria (1000 mg/dL) and abundant ketonuria (>80 mg/dL).
Collateral history obtained from the patient’s family revealed that her diabetes home regimen included insulin glargine 25 units subcutaneously daily, metformin 1000 mg twice daily, glipizide 10 mg daily and empagliflozin 25 mg daily. Her last confirmed intake of oral medications had been on the day prior to presentation. Moreover, it is worth mentioning that the patient was not receiving any enteral nutrition since admission and her diabetes was only being treated with correctional sliding scale insulin while in the intensive care unit. This constellation of information and laboratory findings raised concern for euglycemic diabetic ketoacidosis in the setting of SGLT-2 inhibitor use. The patient was therefore treated with an intravenous insulin infusion. Dextrose-containing maintenance fluids were added to avoid hypoglycemia. Ketoacidosis resolved over 48 hours (see evolution in Table ). The patient was eventually transitioned to subcutaneous basal-bolus insulin regimen and started on tube feeds. No relapse of her EDKA occurred for the remainder of her hospital stay. |
pmc-6581414-1 | First event
A 17-year-old male presented for evaluation with an episode of horizontal diplopia to his doctor in his home country. He was "unable to move his right eye outwards." He did not complain of ear pain, headaches, nausea, neck pain, or vomiting. His symptoms resolved spontaneously in two to four weeks. Despite a thorough workup, no etiology was found and a diagnosis of right cranial nerve (CN) VI nerve palsy was made.
Second event
At the age of 21, the same patient presented with a left facial droop, decreased sensation on the left side of the face, drooling while drinking liquids, and a diagnosis of left V and VII cranial nerve palsy was made. At the time he complained of nasal congestion, coughing, and fatigue. He had no diaphoresis, fever, anorexia, headaches, nausea, abdominal pain, bowel pattern changes, chest pain, chills, arthralgia, joint swelling, myalgia, neck pain, rashes, sore throat, swollen glands, urinary symptoms, vertigo, visual changes, or vomiting.
On examination, his vital signs were normal. On general exam, he appeared well-developed, well-nourished and in no apparent distress. Neurological examination showed normal mental status, no meningeal signs, and no focalities except for facial asymmetry, and weakness involving the eyebrow, upper eyelid as well as decreased sensation across all three branches of the trigeminal nerve (Table ).
He was diagnosed with Bell’s palsy and treated with prednisone for five days with complete resolution of symptoms.
Third event
He returned to the emergency room (ER) six months later with a sudden episode of double vision. He had some upper respiratory symptoms four days prior to the onset and was treated with amoxicillin-clavulanic acid. He had no associated pain, history of recent head or neck trauma, numbness or tingling of the face, facial asymmetry, or trouble swallowing or with speech. He denied visual aura, decreased vision, or other visual complaints. There was no diurnal fluctuation. The general exam was normal. His speech was fluent without any paraphasic errors and his comprehension was intact. The cranial nerves were intact except for left IV cranial nerve palsy.
Given his recent history of sinusitis, cavernous sinus thrombosis was considered but magnetic resonance imaging/ magnetic resonance venography (MRI/MRV) did not show evidence of thrombosis, demyelinating condition, tumor or bleeding. It only showed a Rathke cyst in the pituitary gland that was not compressive of any anatomic areas and was thought to be incidental. He was diagnosed with left IV cranial nerve palsy.
Past medical history revealed hypertension treated with enalapril with good control. He had traveled to Colorado, USA twice in the last two years to visit his relatives. There were no risk factors for HIV.
Extensive workup was done, including tests for Lyme (B.burgdorferi) IgG, IgM by Elisa and Western blot, comprehensive respiratory panel, complete blood count (CBC) and differential, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), basic metabolic panel, thyroid-stimulating hormone (TSH), T4, antinuclear antibody (ANA) screen, AChR Ab, angiotensin-converting enzyme (ACE), muscle-specific kinase (MuSK), hepatitis C virus (HCV), HIV, varicella zoster virus (VZV) antibody IgM and IgG, interferon-gamma release assays (IGRAs), chest X-Ray (CXR), head MRI and cerebrospinal fluid exam (CSF) (Tables -).
Varicella-zoster IgG and IgM antibodies were positive twice, with IgG antibody level being 3.97 and IgM 2.18 (ISR > or = 0.9 Positive). The antibody levels were followed and a gradual decrease in IgM levels over the next five months was noticed (2.18, 2.06, 1.38, 1.22). This time he did not receive any treatment; however, his symptoms improved spontaneously. Furthermore, varicella zoster virus (VZV) PCR was negative in the CSF. |
pmc-6581534-1 | A 53-year-old man manual worker with a 13-year history of gout in his right hallux presented to his general practitioner with right knee pain, stiffness, and giving way with no history of trauma. He had been taking allopurinol for 11 years. He drank 10 to 12 units of alcohol per week and his body mass index was 24.4. On examination, he had anterior knee pain and crepitus was felt from the patellofemoral joint. He had a range of motion from 0 to 90 degrees.
A magnetic resonance imaging (MRI) was performed and reported a grossly abnormal patella tendon showing heterogenous characteristics with areas of architectural distortion and altered signal in all sequences. The appearances were not typical for a tendinosis but more in keeping with findings seen in gout (
).
The patient was commenced on anti-inflammatory medication in addition to his regular allopurinol and referred to an orthopaedic knee surgeon. At assessment, he was found to be significantly compromised by his knee. He was unable to ride a pushbike, walk with his dog, or even get out of a chair. Plain films showed calcification within his patellar tendon (
).
A multidisciplinary discussion with rheumatology and radiology consultants confirmed that the likely diagnosis was a tophaceous gouty deposit within the patella tendon. His uric acid level was 560 μmol/L (above the target of <300 μmol/L set by the British Society for Rheumatology [BSR])
and estimated glomerular filtration rate was 52 mL/min. He was referred to rheumatology who advised increasing the dose of allopurinol. A subsequent ultrasound (US) scan showed the superficial fibers of the patellar tendon relatively intact, but within the deep fibers, there were multiple hyperechoic areas with distortion of the tendon architecture. There was no significant cyst. A computed tomography (CT) scan demonstrated a markedly thickened patellar tendon with areas of mineralization within the tendon itself (
). He was seen in a complex knee clinic with three consultant orthopaedic knee surgeons present. With the patient being fully informed about the risk of surgery and patellar tendon weakening and disruption, he was added to the list for open surgical excision of gouty tophus 18 months from initial presentation. His medical management of 200 mg/d of allopurinol had brought his uric acid down to 366 μmol/L with no side effects, but this was still above the BSR guidance. Subsequently, his allopurinol was increased to a daily dose of 300 mg.
Surgery was performed with the tourniquet inflated at 300 mm Hg for 20 minutes. A midline skin incision was utilized, and the paratenon visualized and incised longitudinally. It was then developed as a definite layer following which the patellar tendon was encountered. The patellar tendon was incised longitudinally and stay sutures placed on either side of the tendon. With gentle traction, the deeper diseased tendon along the lower half of the patellar tendon could be exposed and excised with sharp dissection (
). The excised tissue was sent for histology (
). Finally, a bony spur was encountered, and this was excised with a nibbler. Postoperatively, the patient was allowed to fully weight bear, at his level of comfort. At 6-week review, the wound had healed with no postoperative complications .The patient was able to perform a straight leg raise and manage a full range of pain-free knee movement. His Oxford Knee score was 45. |
pmc-6581659-1 | A primigravid 24 year old female 1.5 hours post-partum was referred to the emergency department from the community health center with total uterine inversion and hypovolemic shock. The patient had given birth vaginally with a midwife wherein during the third stage of labour while placental traction was performed to remove the placenta a large mass emerged through the vaginal passage with the placenta. Afterwards, the patient was reported to be bleeding profusely and soon lose consciousness.
On arrival at the emergency department, the patient was anemic and unresponsive with active vaginal bleeding. Physical examination revealed hypotension (blood pressure 80/60 mmHg), tachycardia (138 x/min) and tachypnea (26x/min). Conjunctiva was anemic with perioral cyanosis, cold & mottled extremities and prolonged capillary refill time (> 3 seconds). Inspection of the genitalia revealed total uterine inversion with perineal lacerations ().
Immediate bloodwork at time of admission was performed which revealed anemia (haemoglobin 5.9 g/dL, hematocrit 17.4%, erythrocyte 2.07 million/uL) and leukocytosis (22.000/uL). Normal thrombocyte level (358.000/uL) was found.
The patient was treated by fluid resuscitation with colloids and crystalloids, blood transfusion and uterotonics. We successfully performed manual reposition of the uterus followed by internal bimanual compression for 15 minutes, however profuse hemorrhage was still observed due to uterine atony. Therefore balloon tamponade was placed to stop the hemorrhage and reduce risk of recurrence. The patient was then stabilized; no surgical management or hysterectomy was required. Perineal repair was subsequently performed once bleeding was managed.
Post-transfusion of 4 packed red cells, bloodwork was repeated which showed hemoglobin of 10 g/dL, hematocrit 29%, erythrocyte 3.66 million/uL, leucocyte 20.900/uL and thrombocyte 159.000/uL. Patient’s hemodynamic also became stable and regain consciousness. Three days post admission, patient recovered without complications. She was discharged with oral antibiotics and pain medication. |
pmc-6581709-1 | Patient 1, a 67-years-old (at day of hospitalization) right handed man, was hospitalized in 05/2013 with multiple cerebral infarctions in the right posterior cerebral artery territory. Stroke MRI showed ischemic lesions in the right thalamus, parts of the internal capsule, and the medial occipitotemporal gyrus (). In addition, small subacute focal occipital and cerebellar lesions were observed on the left side. The initial neurological examination showed minimal motor deficits and severe sensory loss in the upper left extremity, with a National Institutes of Health Stroke Scale [NIHSS; Brott et al. ()] of 4/4 points for the left arm and 2/2 points for severe sensory loss. Following 6 weeks of inpatient neurorehabilitation, the patient was discharged with small improvements of his motor and sensorimotor deficits. On enrollment in this study, 47 months after the stroke, the patient is able to perform fine motor tasks with the left (contralesional) hand, scoring 9/14 points on the hand section of the Fugl-Meyer Assessment of the Upper Extremity [FMA-UE; Fugl-Meyer et al. ()]. The patient is able to use the left (contralesional) hand in daily life to grasp and manipulate objects. However, when the patient does not direct attention to the grasp, this may result in an unintentional release of the object or increased grip force. The patient reported subjective discomfort with tactile localization for the left (contralesional) hand. No other neurological deficits were observed by the neurological examination on study enrollment. |
pmc-6581709-2 | Patient 2, a 68-years-old (at day of hospitalization) right handed woman, was hospitalized in 12/2016 following an acute right middle cerebral artery infarction. Ischemic lesions were detected in the right inferior frontal gyrus (pars opercularis), insula, lateral parts of the pre- and post-central gyrus, superior temporal gyrus, supramaginal gyrus, and corona radiata (). On admission, the patient suffered from severe motor deficits (NIHSS left arm: 4/4 points) and severe sensory loss (NIHSS sensory: 2/2 points) of the upper extremity. Twelve weeks of inpatient neurorehabilitation resulted in significant improvements of motor function, while the somatosensory deficits persisted. When the patient is enrolled in this study 12 months post-stroke, fine hand movements are possible according to the FMA-UE (hand section: 12/14 points). The patient is able to use the left (contralesional) hand in daily life and has sufficient motor strength to hold and manipulate objects. When out of his visual field, the hand would spontaneously release a grasped object without the patient's awareness. The patient reported perceiving severe localization deficits for the left (contralesional) hand. On study enrollment, no other neurological deficits were observed by the neurological examination. |
pmc-6581872-1 | Here we present an exceedingly rare case of buccal oncocytoma in a 14-year-old boy who presented to the Department of ORL Head and Neck Surgery with right buccal swelling for 6 months The swelling was progressively enlarging in size. There was no history of associated pain. There was no history of dysphagia. On examination, there was a single cystic swelling in right cheek around 2*2 cm2 with ill-defined margins (). It was nontender and palpable bimanually. Rest of the Oropharynx and laryngopharynx revealed no abnormality. There were no palpable neck nodes. His vitals were stable with normal blood parameters. He underwent a cytological examination of the mass which reported it as a chronic granulomatous lesion. CT scan of head and neck revealed well defined cystic lesion measuring 2.6*21*19 mm3 lesion in the right buccal space arising from the buccinator muscle and displacing the zygomaticus major (). With the findings above he was posed the provisional diagnosis of the right buccal cyst and planned for excision biopsy under General Anesthesia. Surgery was performed by our team of surgeons of ORL Head and Neck Surgeons. We preferred the intraoral approach. Intraoperatively there was a well defined cystic lesion measuring around 3*3 cm2 in the right buccal space. The cyst contained thick mucinous fluid. The specimen was sent for histopathological examination. Findings of the histopathological examination were consistent with oncocytoma (). He was kept on intravenous antibiotics. The postoperative period was uneventful with mild soft tissue swelling over the operated area without any collections. He was discharged on the 7th postoperative day. On subsequent follow up 1 week later, swelling over the buccal region had subsided. The intraoral surgical wound had healed. He was further followed up after 3 months. There were no signs of recurrence or disease progression. |
pmc-6581979-1 | 46-year-old female with past surgical history of Hartmann’s procedure on 2017 for abscessed and obstructive adenocarcinoma of the sigmoid. Histopathological study confirmed low-grade mucinous adenocarcinoma of sigmoid colon with involvement of all layers and perforation of the visceral peritoneum, pT4pN0. K-RAS gene mutation was present thus chemotherapy with capecitabine was completed. Hartmanns’s reversal procedure was performed months later.
Thereafter 18-months-postoperative follow up appointment, computed tomography (CT) revealed iliac lymphatic recurrence. FOLFOX and FOLFIRI-aflibercept chemotherapy were provided. Abdominal CT control confirmed the persistence of lymphatic disease and target sign in small bowel suggesting intussusception as well.
Forty-eight hours later, the patient presented to emergency department complaining of abdominal pain and distension, lack of elimination of flatulence and vomiting. An abdominal X-ray showed dilated bowel loops with air-fluid levels. Blood test revealed normal white cells level, and a serum-C-reactive protein of 206 mg/L. Abdominal CT evidenced a complete bowel obstruction secondary to small bowel intussusception (). The laparotomy confirmed small bowel obstruction, dependent on intussusception at 50 cm from the ileocecal valve (: intraoperative findings) and the lymphatic recurrence as well. Small bowel resection with mechanical side to side anastomosis were performed. The histopathological analysis confirmed primary small bowel mucinous adenocarcinoma with lymph node metastasis (stage IIIB, T3N1M0). Consecutive both radiotheraphy and chemotherapy with FOLFOX were concluded.
After eight months on follow up, the patient had an elevation of tumor markers level. Abdominal CT showed left iliac lymph node disease, and PET Scan settled extra focus at retroperitoneum. The patient is about to start additional chemotherapy treatment. |
pmc-6581982-1 | A 46-year-old female underwent a health examination with no complaint. No remarkable family history was reported. Her vital signs and blood tests were normal. Examination of the abdomen revealed no pain. However, following an abdominal ultrasonography, a solid mass was observed in close approximation to the kidney. The mass did not involve the abdominal cavity’s wall (). A further evaluation by computed tomography showed the presence of a 38 × 25 mm heterogeneously enhancing mass, with mottled calcifications and a cystic portion arising from small bowel mesentery (a). A low intensity mass of small bowel mesentery was observed by magnetic resonance imaging (T2 WI) (b). We diagnosed either sarcoma of the mesentery or gastrointestinal stromal tumor. The patient underwent a single incisional laparoscopic curative resection of the tumor. During the operation, the tumor was identified in the small bowel mesentery. It did not involve the stomach, intestine and marginal vessel (). The resected tumor measured showed 38 × 25 × 13 mm. Externally, the tumor had a smooth surface. Histopathological findings revealed nests of round to oval cells. The focal area showed the presence of more atypical cells with surround osteoid formation (). The final histologic diagnosis was of primary extraskeletal osteosarcoma arising from the mesentery. The patient underwent an uneventful postoperative course. She did not receive chemotherapy during her follow-up and had no recurrence 10 months post-surgery. |
pmc-6581983-1 | A 38-year-old lady presented with frequent attacks of right hypochondrial pain for the last 4 months, the pain was mainly at the night time and was associated with nausea, no vomiting, and no fever.
The patient had no history of any medical diseases, and the past surgical history was negative.
Ultrasound of the abdomen showed distended gall bladder with 1.3 cm gall bladder polyp at the region of the fundus.
Advices given to the patient to reduce the fatty meals and antispasmodic medications prescribed with little improvement. Decision done for laparoscopic cholecystectomy. During surgery a duplicated gall bladder found with single cystic duct. Successful surgery done and the gall bladder sent for the histopathological examination which showed a benign gall bladder polyp (, , ).
There were no post-operative complications and the patient discharged on the third day. |
pmc-6581984-1 | A 81-year-old male was victim of an accidental fall from a height of 5 m. The patient referred bilateral groin and thigh pain, clinical examination showed inability to actively move the legs and pain on passive movement. The radiographic studies showed a bilateral fracture of the femoral shaft, and a bilateral Robert Mathys (RM®) cementless total hip arthroplasty. The bone lesions were classified as Vancouver type-B2 periprosthetic femoral fracture ().
The patient had a body mass index (BMI) of 33 kg/m2 and a notable comorbilities. On the right hip, a RM® cementless total hip arthroplasty (isoelastic polyacetal stem with stainless-steel head and polyethylene cementless acetabular cup) was implanted, with 24-years follow-up. On the left side, the anteroposterior radiograph showed also a RM® cementless total hip arthroplasty, with 21-years follow-up. On both sides it was possible to observe a biological process of acetabular polyethylene wear, instability of the femoral stem with broken femoral screws, and Paprosky type II femoral osteolysis ().
The fractures were treated with open reduction and fixation with a distal femur locking compression plate (LCP®), with a combination of 3.5 mm nonlocking and locking screws. Therefore, a right distal LCP® plate was applied on left side and a left distal LCP® plate was used on the right side. The femoral stem was easily perforated with a 3.2 mm drill because the implant is composed by a polymer (), a polyacetal resin, with a stainless steel core to avoid over-elasticity in the neck region []. The fractures sites were augmented with criopreserved morselized cancellous bone allografts from the Bone and Tissue Bank of our institute []. On the right side a criopreserved structural fibular bone allograft was also applied on the anterior surface of the femur and was fixed with two cerclage wires.
The surgery was performed in the lateral decubitus, in two phases. First the right femur was operated, then the patient was repositioned to operate the left side. The surgery was performed without the use of a pneumatic tourniquet. The time of the surgery was 2 h and 15 min. Using a Cell-Saver System® the total blood loss was 250 cc. No intraoperative difficulties in patient management were found.
No complications were reported in the perioperative course or during the hospitalization period. The postoperative course showed no problems with respect to the hips. The patient was submitted to an intensive rehabilitation protocol included early mobilization and walking with two crutches.
At 4-months follow-up, the patient presented stable hips and the radiographs showed signs of bone union of the fractures. He reported moderate pain, and some limitation of ordinary activity.
At 12-months follow-up, the patient presented an asymptomatic hips and expressed high degree of satisfaction with surgery result. He reported no pain in his thighs. The femoral radiograph showed consolidation of both fractures and the fibular structural allograft had no signs of bone resorption (). The patient was clinically able to walk without external support. |
pmc-6582073-1 | A 71-year-old man was admitted to our clinic with abdominal pain. Contrast-enhanced computed tomography (CT) showed a tumor located at the caudate lobe that involved the IVC and the roots of the three major hepatic veins (Fig. a, b). The diagnosis of an advanced intrahepatic cholangiocarcinoma was made. Neither lymph node metastasis nor distant metastasis was detected. He had no jaundice and was in good general condition.
The only possible procedure to achieve curative resection was a left hepatic trisectionectomy combined with resection of the IVC and the three major hepatic veins. The volume of the right posterior sector was 333 cm3 (32.3% of the whole liver). The plasma disappearance rate of indocyanine green was 0.154. Portal vein embolization (PVE) of the left and right anterior portal veins was performed to increase the volume of the right posterior sector. In addition, as this case had a “thin” IRHV, embolization of the RHV was planned, with the aim of simplifying the surgical procedure by preserving the IRHV. Seven days after the PVE, the RHV was embolized using an Amplatzer vascular plug-II® (St. Jude Medical, St. Paul, Minnesota, USA), which was expected to develop collaterals from the RHV to the IRHV (Fig. a, b). To assess the feasibility of RHV resection, we ensured collaterals to the IRHV under balloon occlusion of the RHV. A CT scan obtained 29 days after the RHV embolization demonstrated that the volume of the right posterior sector had increased up to 562 cm3 (42.9% of the whole liver) and that the diameter of the IRHV had enlarged to 7.7 mm, from 3.5 mm before embolization (Fig. a, b).
Surgery was performed 35 days after the RHV embolization. A left hepatic trisectionectomy with partial resection of the caudate lobe was performed. The involved IVC and RHV were also resected en bloc, and the IRHV was preserved as planned. Before the involved IVC was resected, we placed the temporal venous-venous bypass between the IVC distal to the renal veins and the right atrium. The resected IVC was reconstructed using a polytetrafluoroethylene (PTFE) vascular graft (Fig. a, b). The operative time was 867 min, and blood loss was 12,428 mL.
Histologically, the tumor was a moderately differentiated adenocarcinoma that had invaded the IVC and all three major hepatic veins and exhibited regional lymph node metastases (Fig. ). Postoperatively, maximum serum total bilirubin concentration was 5.8 mg/dl (grade B liver failure). Mild ascites developed, but it was well controlled by diuretics. He was discharged from the hospital in good health on postoperative day 36 and enjoyed an active social life, but he died of recurrence 18 months after the surgery. |
pmc-6582224-1 | A 63-year-old, right-handed man exhibited transient episodes of amnesia. He also showed independent, short-duration loss of awareness with oral automatism. He had therefore visited a local hospital, where brain magnetic resonance imaging (MRI) had revealed CM in the right amygdala (). As the frequency of loss of awareness and transient amnestic episodes increased and memory disturbances exacerbated over a period of years, he was diagnosed with early-stage AD concomitant with temporal lobe epilepsy at the hospital. He was therefore referred to our epilepsy center at 64 years old.
Seven-day scalp video-EEG performed at our epilepsy center captured no interictal epileptiform discharges, impaired awareness seizures, or oral automatisms. However, based on the clinical history and right amygdala CM, we diagnosed epileptic amnesia (EA) and prescribed levetiracetam. Levetiracetam mildly decreased the frequency of intermittent amnesic episodes, but did not resolve them completely. As we had started speculating that the CM in the right amygdala might have contributed to EA and cognitive deterioration, he underwent neuropsychological examinations: preoperative Mini-Mental State Examination (MMSE) score, 25/30; Hasegawa's dementia scale-revised (HDS-R), 22/30; Weschler memory scale (WMS)-III, verbal memory 79, visual memory 68, total memory 72; trail making test (TMT)-A, 1 min 27 s; TMT-B, 3 min 37 s. We planned minimally invasive intraoperative subdural electrode (SE) recording directly from the parahippocampal area via a small burr hole and small skin incision. We had decided in advance that if epileptiform discharges were obtained from the SE recording, we would proceed to remove the CM. If no epileptiform discharges were obtained, we would just withdraw the SE and close the incision.
Intraoperatively, the SE recording from the right parahippocampal area () showed frequent epileptiform discharges (). We therefore selectively removed the CM under a transcortical approach at 65 years old. After removal of the CM, the SE recording showed no interictal discharges ().
Postoperatively, the patient remained free from transient amnesic episodes and impaired awareness seizures. Four months after the surgery, neuropsychological examinations conducted without changing any medication showed: MMSE, 26/30; HDS-R, 26/30; WMS-R, verbal memory 82, visual memory 68, total memory 74; TMT-A, 42 s; and TMT-B, 2 min 30 s (). Postoperatively, the patient could walk, talk, and eat faster and became more sociable.
The neuropathological examination showed CM, with senile plaques found in the normal cortex surrounding the CM according to periodic acid methenamine silver staining and immunohistochemical staining (). |
pmc-6582470-1 | We report a 26-year-old female and her 28-year-old healthy male partner, who experienced difficulties in becoming pregnant since 2015. Female patient had a regular menstrual cycle, but was previously diagnosed with endometriosis in 2012 following laparoscopy, for which she received treatment with goserelin acetate implant (Zoladex®). In January and October 2016, the couple experienced two first trimester miscarriages after natural conception at 5/6 weeks (gestational sac and yolk sac were visible by obstetric ultrasonography) and at 4/5 weeks (only gestational sac was visible) of gestation, respectively. The couple then turned to assisted reproduction in 2017 due to fertility issues. Because of history of endometriosis, the female patient underwent laparoscopy again in April 2017, but no endometriotic lesions were found and fallopian tubes were patent. The female patient was then followed up for multiple cycles for the presence of a dominant follicle. In addition, she was administered with alpha chorionic gonadotropin (Ovitrelle®) and dihydrogesterone (Duphaston®) but failed to conceive. In September 2017, the couple enrolled into IVF/PGT-A program at fertility clinic at West-Tallinn Central Hospital for elective embryo transfer to assist in achieving a successful pregnancy. An informed consent was also obtained, allowing to use supernumerary/affected embryos for research purposes.
Controlled ovarian stimulation was performed using recombinant follicle-stimulating hormone, followed by a gonadotropin-releasing hormone (GnRH) antagonist protocol. Final oocyte maturation was triggered by human chorionic gonadotropin administration 36–38 h prior to oocyte retrieval. In total 19 oocytes have been retrieved and all of them were fertilized by conventional IVF. The presumed zygotes were then cultured in a SAGE-1 single step media (Origio, Denmark) until day 5 blastocyst stage. Subsequent embryo morphological evaluation was performed according to the criteria set by Gardner and Schoolcraft []. Trophectoderm (TE) biopsy was performed on four embryos that reached the blastocyst stage using RI Saturn 5 Active™ Laser and on average 5–10 cells were aspirated per embryo. Following TE biopsy, all blastocysts were vitrified using MediCult Vitrification Cooling medias (Origio).
For PGT-A, commercially available VeriSeq PGS kit (Illumina Inc., USA) was used for next-generation sequencing (NGS)-based aneuploidy screening. Briefly, TE biopsies were whole-genome amplified (WGA) according to ligation-mediated PCR-based SurePlex protocol (Illumina Inc., USA). The quality of WGA products was controlled on 1.5% agarose gel and the amount of amplified material was quantified by Qubit dsDNA HS Assay kit (Thermo Fisher Scientific, USA). Next, successfully amplified samples were used for library preparation, according to the manufacturer’s VeriSeq PGS kit protocol, and were sequenced on the Illumina MiSeq system. Subsequent CCS was performed using Illumina BlueFuse Multi v4.3 software with an embedded aneuploidy calling algorithm. Based on TE biopsy results, embryo classification was performed according to Preimplantation Genetic Diagnosis International Society (PGDIS) guidelines and recommendations for embryo prioritization (PGDIS, 2016).
For blood cell karyotyping, conventional GTG-banding technique (G-bands by trypsin using Giemsa; band level 550) was used for staining metaphase chromosomes from peripheral blood lymphocytes. Chromosome aberrations were classified according to the International System for Human Cytogenetic Nomenclature (ISCN2016). |
Subsets and Splits
Exclude ER emergencies
Retrieves 100 descriptions that do not contain the terms 'ER' or 'emergency', providing a basic filter of the dataset.