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pmc-6497199-3 | An 86-year-old female with a past medical history of hypertension and dyslipidemia was brought to our ED by ambulance from the same family gathering after ingesting the same honeycomb cake. She complained of feeling unwell with lightheadedness, headache, recurrent vomiting, shortness of breath, and chest pain followed by a syncopal episode. Paramedics reported that the patient was cyanotic with pulse oximetry 70% on 12 liters non-rebreather mask and hypotensive with systolic blood pressure 80 mmHg. On arrival to the ED, she was awake, alert and ill-appearing with the following vital signs: pulse oximetry 85% on non-rebreather mask, respiratory rate 25 breaths per minutes, pulse rate 98 beats per minutes, and blood pressure 115/72 mmHg after one liter normal saline bolus. Her physical exam was significant for severe cyanosis, tachypnea, clear lungs to auscultation, and tachycardia on cardiovascular examination. Given the concurrent presentation with the other two patients from the same party, we treated the patient with one dose of methylene blue prior to obtaining initial methemoglobin levels.
Her vital signs stabilized on reevaluation after 30 minutes of methylene blue administration. She reported complete resolution of symptoms including chest pain, shortness of breath, and headache. Her pulse oximetry improved to 92% on room air. Her comprehensive metabolic panel results were within normal limits except for a slight elevation of creatinine from her baseline. Troponin I levels were negative. Initial methemoglobin levels pretreatment were unknown, but levels obtained at 30 minutes and 10 hours after methylene blue administration were 6.7% and 0.7%, respectively. The patient was admitted to telemetry for further observation, but once there she became hypotensive with blood pressure 90/50 mmHg despite administration of two additional liters of normal saline. She was then transferred to the intensive care unit (ICU) for monitoring. She remained asymptomatic on room air with resolution of hypotension after receiving intravenous fluids at 100 mL per hour in the ICU overnight and was downgraded back to telemetry in the morning. She had a full recovery and was discharged home the following day. |
pmc-6497200-1 | A 58-year-old male who denied any past medical history presented to the emergency department (ED) with left lower extremity weakness for the prior 30 minutes. He stated that he had sudden onset paralysis, which prompted him to go to the ED for evaluation. On further inquiry, the patient also described having central chest pain radiating to the back that seemed to coincide with the paralysis. He denied shortness of breath or any other neurological deficits.
Upon arrival to the ED, the patient was diaphoretic, pale, and in acute distress. Vitals at the time included a pulse of 74 beats per minute, blood pressure of 166/97 millimeters of mercury in the right upper extremity, respirations of 20 breaths per minute, oxygen saturation of 97% on room air, and an oral temperature of 97.9 degrees Fahrenheit. His pertinent physical exam findings included bilateral diminished radial pulses and 0/5 strength in his left lower extremity. His lungs were clear to auscultation bilaterally and there was no appreciable murmur. No chest radiograph (CXR) was obtained.
An electrocardiogram (ECG) was performed () that demonstrated an acute inferior and posterior ST-segment elevation myocardial infarction (STEMI), which prompted activation of a “code STEMI.” However, while he was still in the ED, we performed a POCUS. Ultrasound revealed right ventricle akinesis consistent with an acute MI and a dissection flap of the aortic arch, but was negative for pericardial effusion or tamponade at that time (). Based on these ultrasound findings and with cardiology at bedside, the code was cancelled as it was agreed that percutaneous coronary intervention should not be performed and instead cardiothoracic surgery be emergently paged. The patient was immediately brought to the radiology suite for an emergent computed tomography angiogram (CTA) of the chest and abdomen.
Unfortunately, while on the table prior to imaging acquisition, the patient became bradycardic, unresponsive, apneic, and was found to be in pulseless electrical activity arrest. CTA was aborted and cardiopulmonary resuscitation was initiated. He was brought to the resuscitation bay where repeat POCUS demonstrated a large, complex pericardial effusion with right and left ventricular collapse representing hemorrhagic tamponade (). An emergent pericardiocentesis was performed with ultrasound guidance without success. Given hemorrhagic tamponade from AD and failed pericardiocentesis, the resuscitation was deemed to be medically futile and time of death was called. |
pmc-6497201-1 | A previously healthy and fully vaccinated three-year-old female was brought by her parents to the ED with a rash that had been worsening over a five-day period. The mother of the patient reported a fall from playground equipment with resulting abrasion just prior to the onset of the rash. In appearance, the rash was macular, mildly erythematous, and located over the child’s trunk and face. Desquamation of skin surrounding the abrasion occurred after subsequent removal of an adhesive bandage applied to the area. The child had two healthcare visits before presenting to our ED. A few days after the fall, the patient’s primary care physician diagnosed her with an allergic reaction and treated her with diphenhydramine. Further worsening of the rash prompted the parents of the patient to seek care at an outside ED, where she was again diagnosed with an allergic reaction, given diphenhydramine, and also treated with intravenous (IV) fluids. Of note, after this last visit to the ED, further desquamation occurred with removal of adhesives used to secure a peripheral IV on her arm.
In our department the parents denied fevers but reported decreased per os (PO) intake, with only one episode of urination in the prior 24 hours, along with worsening fatigue. The child also reported some dysuria and odynophagia. She denied respiratory symptoms, vomiting or diarrhea. On physical examination, the child was mildly tachycardic with no other vital sign abnormalities. She appeared fatigued but was interactive during the examination. She had areas of slightly edematous erythema around her periorbital areas, cheeks, neck, upper back, and inguinal area with areas of surrounding desquamation ( and ). The original abrasion was surrounded by more pronounced edema and erythema consistent with a small, localized cellulitis. There was no evidence of mucosal involvement on examination of the pharynx and vaginal introitus. The child received fluid resuscitation with a 20 milligram- per-kilogram bolus of IV normal saline, blood cultures were taken, and IV clindamycin initiated. Although there was no mucosal involvement on our examination, there was higher concern for Stevens-Johnson or TENS, since the child reported dysuria and odynophagia. The dermatology service was consulted and recommended admission to the pediatric intensive care unit (PICU) and the addition of ceftaroline to her IV clindamycin. The child was admitted to the PICU, where she received continued IV antibiotics, fluid resuscitation and wound care for the desquamating lesions. By hospital day three, she had no further wound desquamation and had improved urine output. She was discharged after a five-day hospital stay with a seven-day course of PO cephalexin. |
pmc-6497202-1 | A four-year-old girl presented to the emergency department with several episodes of vomiting; on questioning, she stated that she had swallowed something at daycare. Her parents were unsure whether she had access to button batteries. She had no respiratory distress on physical exam. The hospital obtained a single plain radiograph, an anteroposterior (AP) view of the chest (), and referred her to our tertiary center. The patient had no lateral film, but on high-contrast windowing of the film, which had been taken at a peak kilovoltage (kVp) of 100, the visible face of George Washington identified the object as a quarter ( and ). The quarter was removed endoscopically without complication. |
pmc-6497203-1 | After falling off a mountain bike down an incline into some brush, a 49-year-old male mountain biker presented to an outside ED with normal vitals, severe vertigo, nausea, intractable vomiting, profound hearing loss, and tinnitus. A CT was performed, which showed opacification of the ear canal, but did not comment on any abnormalities of the inner ear. The patient was transferred to our facility for further management. On examination, there was a spontaneous right-beating nystagmus and the facial nerve was intact. A tree twig was embedded in the left external auditory canal, obscuring visualization of the tympanic membrane.
Temporal bone CT demonstrated a linear foreign body projecting from the external auditory canal to the oval window, and an additional, separate small foreign body projecting into the vestibule. Presence of extensive intralabyrinthine air was detected radiographically (). On axial view, air bubbles were seen in the vestibule, posterior semicircular canal, and the scala vestibuli compartment of the cochlear basal turn, as well as in the lateral and superior semicircular canals (). Preoperative audiogram conducted at bedside revealed normal hearing on the right side and moderate-to-severe mixed hearing loss on the left.
The patient was diagnosed with a traumatic PLF with extensive pneumolabyrinth due to penetrating temporal bone injury and was taken urgently to the operating room less than one day after his inciting injury. A three- centimeter tree twig was lodged in the ear canal and found to be penetrating the tympanic membrane. Postauricular approach included mastoidectomy and intraoperative assessment of the middle ear ossicles and extent of injury. The long process of the incus was dislocated but still attached to the malleus, the stapes was deeply embedded into the vestibule, and the oval window was completely open but covered by blood clot. All penetrating foreign bodies were extracted. Temporalis fascia was used to seal the oval window and a stapes prosthesis was placed. The tympanic membrane perforation was repaired.
Postoperatively, the patient had rapid and significant improvement of his vertigo. On physical examination, there was minimal spontaneous nystagmus. A four-week postoperative audiogram revealed a mild-to-moderate mixed hearing loss in the left ear with continued improvement at six months. |
pmc-6497204-1 | A 39-year-old Hispanic male with no past medical history presented to the emergency department (ED) with a chief complaint of “allergic reaction.” Pertinent review of systems included several weeks of left facial and neck swelling, pharyngitis, non-productive cough, and rhinorrhea. He was evaluated multiple times in the urgent care setting and treated with several different antibiotic regimens for bacterial pharyngitis. He later developed bilateral conjunctivitis, oral ulcers, and a solitary penile lesion. Outpatient medications were broadened to include antivirals, antifungals, and steroids. Due to persistence of symptoms, along with the development of hematuria and rectal pain, the patient sought evaluation in the ED.
Physical examination revealed bilateral, non-purulent conjunctival injection, multiple non-painful ulcerative oral lesions (), tender left cervical lymphadenopathy with edema, and a single non-ulcerative penile lesion with purulent discharge at the glans (). Vitals were within normal limits. Laboratory studies revealed a slight leukocytosis, but the remainder of labs, including inflammatory markers, were unremarkable. Computed tomography of the neck demonstrated left-sided cervical adenopathy suspicious for neoplasm (). |
pmc-6497205-1 | A 46-year-old Asian man with history of hypertension, end-stage renal disease on dialysis, thrombotic stroke, and chronic tobacco use presented to the emergency department (ED) with chief complaint of weakness, lightheadedness, and shortness of breath for two days. He had dialysis one day before, but did not feel better. He developed central chest pain at rest four to five hours prior to arrival, which was worse with deep inspiration. He was seen at an outside hospital and was told he had a pericardial effusion. He was then sent to our ED for higher level of care.
On arrival, blood pressure was 124/89 millimeters of mercury (mmHg), heart rate 120 beats per minute, respiratory rate 18 per minute, oral temperature 37.4° centigrade and oxygen saturation 93% on room air. His body mass index was 23 kg/m2. His physical exam was notable for warm and dry skin, normal mentation, hyperdynamic precordium, normal S1 and S2, and no audible murmur, rub or gallop. There was jugular venous distention while sitting up at 90 degrees, but this was not specifically measured. There were no rales of pulmonary congestion and he had no leg edema or complaints of pain.
POCUS did not reveal circumferential or dependent effusion or tamponade physiology. The bedside image was interpreted as an enlarged right ventricle (RV), nearly twice the transverse dimension of the left ventricle, with a thickened intraventricular septum, suspicious for right heart strain ().
The patient had laboratory studies, electrocardiogram (), anterior-posterior portable chest radiograph (), and computed tomography angiography (CTA) to assess for PE (), among other diagnoses. He was given aspirin, and unfractionated heparin bolus and drip per cardiology recommendations pending CTA, which was done upon admission a few hours after presentation to the ED. He was admitted to the coronary care unit. The CTA then revealed a loculated anterior pericardial effusion, and the thickened septum was determined to be the compressed RV, which had not been appreciated on POCUS.
His initial troponin was 0.23 nanograms per milliliter (ng/mL) (normal < .03 ng/mL) in the ED, and rose to 0.26 upon admission six hours later. This was thought to be due to renal failure and not acute coronary syndrome per the inpatient team. The patient had pericardiocentesis of 630 mL sterile serosanguinous fluid under ultrasound guidance in the cardiac catheterization lab. Initial intrapericardial pressure was 20 mmHg. The cause of the effusion was ultimately attributed to uremia. The patient had no history of infection or cardiac surgery to predispose to loculation. Fortunately, there was no complication of the unnecessary anticoagulation. |
pmc-6497206-1 | A 22-year-old male with a past medical history of pericarditis and pericardial effusion presented to the ED with the chief complaint of facial swelling, which had been present for the prior three weeks. The swelling was predominantly on the right side of his face and upper lip. He had no history of angioedema, had not started any new medications, and was not aware of an environmental exposure that immediately preceded the onset of swelling. In addition to the facial and lip swelling, the patient reported a rash of the same duration on his chest and shoulders. Additional associated symptoms included decreased exercise tolerance, exertional dyspnea, and a single episode of dark, maroon-colored stool. He denied fever, chills, myalgia, arthralgia, chest pain, abdominal pain, nausea, vomiting, odynophagia, dysphagia, and confusion. He was not aware of any sick contacts and he had not traveled recently. He reported that his family did not have a history of chronic illnesses.
Physical examination was significant for a blood pressure of 104/58 millimeters of mercury, a pulse of 96 beats per minute, respiratory rate of 16 breaths per minute, a temperature of 36.8° Celsius, and a pulse oximetry reading of 100% on room air. He was a thin young man who did not appear to be in distress or acutely ill. Bilateral facial edema along with edema of the upper lip was noted (). In addition, his conjunctiva, palms, and soles were notable for pallor. A petechial rash was observed on his upper chest, bilateral shoulders, tongue, and soft palate (). A malar rash was also noted (). The remainder of his examination was normal.
His initial ED evaluation included a chest radiograph, electrocardiogram, and laboratory studies. The results of pertinent laboratory studies are listed in the . Given his severe thrombocytopenia and anemia, thrombotic thrombocytopenic purpura (TTP) was considered and an emergent hematology consultation was obtained. A peripheral blood smear demonstrated 1–2 schistocytes per high-power field, which initially raised concern for a microangiopathic hemolytic anemia. As a result, a hemodialysis catheter was inserted and plasmapheresis was initiated while the patient was in the ED. He received a unit of packed red blood cells along with corticosteroids and was admitted to the medical intermediate care unit.
Workup revealed a positive immunoglobulin G (IgG) Coombs test. He also had a high titer of antinuclear acid antibody and low C3/C4 complements, indicative of an acute exacerbation of an autoimmune disease. The combination of his symptoms, ED workup, and history of pericarditis and pericardial effusion favored the diagnosis of systemic lupus erythematosus (SLE). Within 48 hours after admission, an A disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13) level returned with 78% activity and less than 5% inhibitor. This result was not consistent with the diagnosis of TTP, and plasma exchange was stopped. Ultimately, the hematologist diagnosed Evans syndrome as a presenting feature of SLE. |
pmc-6497207-1 | A 29-year-old man with no significant medical history presented to the emergency department with severe pain, swelling, and inability to move his right knee. He was injured when he extended his right knee to hit a tennis ball after running to the net. On examination, high-riding patellae were found on both the injured and non-injured sides. A lateral view radiograph showed patella alta in both knees (). Magnetic resonance imaging (MRI) was performed to examine the right knee extensor apparatus (). |
pmc-6497208-1 | A two-year-old male presented to the pediatric emergency department for possible foreign body ingestion. Two hours prior to arrival, the child was found with the packaging for 10 button batteries, but his mother was only able to find one battery. The patient had no symptoms. Physical exam was within normal limits. Radiographs () showed six foreign bodies within the stomach and one distally. |
pmc-6497209-1 | A 29-year-old woman with high myopia and a history of bilateral ICLs placed five years previously presented to the emergency department (ED) with a chief complaint of headache and blurry vision in her right eye. The patient stated that the night prior to presentation she noted that her right eye was dilated. She also complained of light sensitivity and mild blurry vision. When she woke up the morning of presentation she noted a dull headache behind her right eye, which she rated a 2/10 on a numeric pain scale. She reported trouble focusing on close-up text but denied other vision decline or diplopia. She denied neck pain, nausea, vomiting, fever, chills, numbness, or tingling. She denied recent trauma, visits to the chiropractor, or use of mydriatic medications. She had been evaluated by ophthalmology six days prior to presentation for similar symptoms and was found to have mild mechanical anisocoria. Given her minor symptoms at that time, it was felt that there was no need for intervention.
Initial examination in the ED revealed a marked anisocoria, with the right pupil larger than the left. The right pupil was mid-dilated and fixed at six millimeters (mm). There was appropriate constriction of the left pupil. The right conjunctiva was injected. Visual acuity was 20/30 in the right eye and 20/20 in the left eye. Intraocular pressure of the right eye was markedly elevated at 44 mm of mercury (Hg). Her remaining neurologic exam revealed no focal deficits. Ophthalmology was consulted. After examining her, they found a right eye with a round, fixed pupil, +1 injection, diffuse microcysts, a shallow anterior chamber, fixed, minor iris bombe, and confirmation of intraocular hypertension. Examination of the left eye demonstrated two peripheral patent iridotomies at 12 o’clock and 3 o’clock and intraocular pressure of 11 mmHg. The patient was diagnosed with acute pupillary block and was administered timolol, acetazolamide, and brimonidine, but the intraocular pressure remained elevated at 35 mmHg. The patient was discharged from the ED directly to an outpatient ophthalmology clinic for urgent procedural treatment of pupillary block.
The patient presented to the ophthalmology clinic and underwent a yttrium-aluminum-garnet laser peripheral iridotomy. The right eye was anesthetized with topical proparacaine and a single peripheral iridotomy was created in the temporal iris. Aqueous humor was visualized to flow through the ostomy from the posterior to anterior chamber and the iris bombe significantly flattened. Immediately post-procedure, topical brimonidine was administered and the intraocular pressure was measured at 17 mmHg. One hour after the procedure, the intraocular pressure was 13 mmHg. The patient was prescribed difluprednate four times daily and brimonidine/timolol twice daily for five days and scheduled for follow-up with ophthalmology in one week.
At one-week follow-up, the patient noted marked improvement of her symptoms. She did not note any further headaches or difficulty with vision. She did, however, note continued mild anisocoria in the dark, and examination confirmed 0.5–1mm right greater than left anisocoria. Due to the persistent anisocoria, the patient was referred to neuro-ophthalmology for further investigation. A neurologic etiology was not identified and the persistent anisocoria was felt to be mechanical. The patient returned to ophthalmology clinic several months after her initial presentation with a subsequent increase in her intraocular pressure and required an additional peripheral iridotomy. She continues to be followed by ophthalmology. |
pmc-6497210-1 | A 49-year-old female presented to the ED after waking up with nausea and abdominal pain followed by multiple episodes of vomiting. Her past medical history included T2DM, diagnosed four years earlier, and hypertension. Antihyperglycemic medications at the time of presentation included insulin glargine 25 units subcutaneous once a day, exenatide 10 micrograms (mcg) subcutaneous twice a day, empagliflozin 25 milligrams (mg) once a day (started four months prior to admission), and metformin 1000 mg twice a day.
Pertinent laboratory values upon presentation to the ED included the following: hemoglobin A1C 10.5% (4.4–5.6%), glucose 251 mg/deciliter (dL) (60–100 mg/dL), chloride 93 millimols per liter (mmol/L) (98–111 mmol/L), carbon dioxide 12 mmol/L (20–30 mmol/L), anion gap 29 (6–14), c-peptide 0.1 nanogram per milliliter (ng/mL) (0.9–6.9 ng/mL), ketone beta-hydroxybutyrate > 2.0 mmol/L (0.02–0.27 mmol/L), serum osmolality 322 milliosmoles per kilogram (mOsmol/kg) (280–295 mOsmol/kg), lactate 2.7 mmol/L (0.4–2.0 mmol/L) and a urine analysis with abnormal glucose of 500 mg/dL and ketones 80 mg/dL, but otherwise unremarkable. She was diagnosed with DKA and admitted to the intensive care unit on intravenous hydration and insulin drip per institution protocol.
DKA resolved two days following admission and the patient was discharged. At discharge, no precipitating factor leading to her DKA had been identified during the hospitalization. There had been no evidence of infection or pancreatitis, and she was discharged on all home medications with an increase in her insulin glargine to 30 units once a day.
She was seen in her primary care clinic six days post-discharge. Additional laboratory values were drawn including glutamic acid decarboxylase (GAD) antibody, which was elevated > 250 units/mL (< 0.5 units/mL). Given that the empagliflozin had been initiated four months prior to her hospital admission and that she had been admitted with euDKA with a glucose level of only 251 mg/dL at presentation, at the primary care follow-up, it was determined that this was a case of SGLT2 inhibitor-induced DKA. She had been managed as a type 2 diabetic for four years, but her low c-peptide level and elevated GAD antibody drawn at this post-discharge follow-up appointment resulted in a change in diagnosis to type 1 diabetes from type 2. All non-insulin antihyperglycemic agents including the empagliflozin that precipitated the DKA were discontinued and she was placed on a basal plus bolus insulin regimen. |
pmc-6497211-1 | A 73-year-old man with rheumatoid arthritis on prednisone (10 milligrams [mg] daily routinely, and increased to 40 mg daily during frequent exacerbations) presented to the emergency department with chills and a leg rash. Two weeks prior, he noticed redness on his right thigh, with black spots developing later. His vital signs were normal, and his physical examination was significant for a 6 × 10 centimeter (cm) red, warm patch with 0.5 cm indurated black papules and ulcers (). His lab work-up was unremarkable. Periodic acid–Schiff–diastase and Gram stains of a punch biopsy sample of one papule demonstrated variably sized yeast and hyphal fungal elements. Purpureocillium lilacinum grew, thus clinching the diagnosis. |
pmc-6497212-1 | A previously healthy 10-year-old boy presented with an acute onset of periumbilical colicky abdominal pain of one day’s duration. It was rapidly progressive and became generalized. This was associated with tactile fever and two episodes of non-bilious vomiting. There was no associated diarrhea. The patient denied any recent sick contacts or overseas travel. At triage in the ED, he was febrile with a temperature of 38.2 degrees Celsius. He was tachycardic with a heart rate of 120 beats per minute and had a blood pressure of 90/61 millimeters (mm) of mercury. He had a respiratory rate of 20 breaths per minute and pulse oximetry was 99% on room air. His peripheral capillary refill time was delayed at three seconds. The triage nurses put him immediately in the resuscitation bay. Physical examination revealed an anicteric, lethargic child with a rigid abdomen and sluggish bowel sounds. Despite having generalized involuntary guarding of his abdomen, the child claimed the pain was “minimal.” However, he was noted to be wincing maximally when his abdomen was palpated over his right hypochondrium. He was clinically in shock and was promptly given fluid resuscitation with a rapid bolus of 20 milliliters per kilogram of normal saline. He responded well to the fluids with improved peripheral perfusion. An upright chest radiograph did not reveal any free air under the diaphragm. A supine abdominal radiograph showed a circular radiopaque structure suggestive of calcification (“stone”) over his right hypochondrium ().
POCUS was performed using Sonosite M-Turbo with a 2–5 megahertz curvilinear transducer. Visual cardiac contractility (parasternal long axis) showed a hyperkinetic left ventricle with good visual contractility. Initially, it was noted that his inferior vena cava was totally collapsed on spontaneous inspiration, which suggested that he was “volume depleted,” given his initial hemodynamic parameters. This improved post-fluid resuscitation. No gross abnormal hepatobiliary or renal abnormalities were noted. Unexpectedly, during the ultrasound examination of his right hypochondrium, a tubular structure measuring 14 mm in diameter with surrounding fluid at its end was noted just inferior to the liver’s surface ().
The tubular structure could be traced caudally to the cecum, suggesting a high ascending retrocecal appendicitis. The complex fluid and loss of the submucosal echogenic layer surrounding the appendix suggested perforation. Further interrogation showed a structure with acoustic shadowing posteriorly suggestive of an appendicolith () in the clinical context.
Ultrasound also revealed features of ileus. Based on these findings, he was admitted to the surgical intermediate care unit with a diagnosis of perforated appendicitis even before any hematological and biochemical laboratory investigation results were made available. After initiating intravenous antibiotics, the surgeons elected to obtain an urgent radiology abdominal ultrasound, which confirmed the findings of the initial POCUS. Soon after, he underwent an uneventful urgent laparoscopic appendectomy. Intraoperatively, surgical examination found that the cecum and appendix were unusually high, in close proximity to the liver’s inferior surface. The retrocecal appendix was noted to be inflamed with mid-shaft perforation. The base of the appendix was healthy. There was spillage of a fecolith into the paracolic gutter, with minimal fluid in the pelvis. Some adhesions were noted between the small bowel and abdominal wall. The rest of bowel, liver, and gallbladder were normal. Post-appendectomy, he was discharged well after a five-day hospitalization. |
pmc-6497214-1 | A 39-year-old male with no past history presented with three months of left inguinal pain and a left groin lump that became progressively larger and more painful. He was seen at another hospital over one month prior where they were unable to manually reduce the lump. He could not recall the computed tomography (CT) findings, and no surgery was performed. Since then, he has experienced persistent left inguinal pain and nausea. He denied fever, vomiting, dysuria, hematuria, penile discharge, testicular pain, or history of sexually transmitted diseases.
Physical exam revealed a firm, tender, and non-reducible mass in the left inguinal canal and along the spermatic cord. Remainder of examination was normal. Complete blood count, basic metabolic panel, lactate, urinalysis and urine culture were normal. CT of the abdomen and pelvis was suggestive of pampiniform plexus thrombosis (). Formal ultrasound images revealed diminished Doppler vascular flow () within the left testicle and prominent, heterogeneous vascular structures seen in the left inguinal canal () that correlated with the CT, indicating pampiniform plexus thrombosis as well. |
pmc-6497512-1 | An 81-year-old male with a past medical history of obesity and diabetes mellitus presented to our hospital with confusion over the past week, new onset black, tarry stools, and foul-smelling urine over the past day. On examination, the patient was hemodynamically stable and was oriented only to person. However, he had a distended and non-tender abdomen with a positive fluid wave sign. The rectal exam was positive for melanotic stools. Laboratory results elucidated pancytopenia with a hemoglobin of 7.1 g/dL, white blood cells of 3200 K/cm3, platelets of 130,000 k/cm3 and an internal normalized ratio (INR) of 1.22. The chemistry panel showed hypoalbuminemia (2.1 mg/dL) and elevated aspartate aminotransferase (AST) of 43 U/L. Urinalysis was abnormal, showing >180 white blood cell (WBC) with positive leukocyte esterase and nitrites. Liver ultrasound evidenced cirrhosis and reversed portal venous flow without thrombus and ascites. The viral hepatitis panel was negative for hepatitis B or C infection. The patient had a Model for End-Stage Liver Disease (MELD ) score of 9 on admission. Octreotide drip, ceftriaxone, and pantoprazole were initiated for upper gastrointestinal hemorrhage. Due to new-onset decompensated liver cirrhosis associated with encephalopathy, lactulose was started. An elevated D-dimer result (1.06 mg/L) was found, and, for this reason, a computed tomography angiogram (CTA) of the chest was done. This was positive for bilateral segmental pulmonary embolism without features suggesting right heart strain. Therefore, the patient was also started on an unfractionated heparin drip.
On the second day of admission, the patient underwent an esophagogastroduodenoscopy (EGD), showing portal hypertensive gastropathy, with one small area that had a fresh blood clot, which was treated with argon plasma coagulation (APC). There was no evidence of esophageal or gastric varices.
On the fifth day of admission, while anti-factor XA level was 0.53 IU/mL (goal antiXa: 0.3-0.7 IU/mL), a bedside ultrasound-guided paracentesis was done. Six liters of ascitic fluid were removed for diagnostic and therapeutic purposes and this was compatible with portal hypertension, with a serum-ascites albumin gradient (SAAG) of 1.8 g/dL and total protein of 2.0 g/dL. Cell count showed spontaneous bacterial peritonitis (with 365 polymorphonuclear cells/mm3), which was treated with intravenous antibiotics. Ascitic fluid cultures showed Escherichia coli, sensitive to ceftriaxone.
On the seventh day of admission, the patient presented acute left flank pain with an associated episode of hypotension. Hemoglobin levels dropped to 5.4 g/dL from 8.2 g/dL the day before. CTA abdomen showed a left retroperitoneal hemorrhage extravasating to extraperitoneal areas (Figure ). There was a suspicion for portosystemic varices within the peritoneum and mesentery. Another finding was a splenorenal shunt measuring 2.2 centimeters (Figure ). There were no signs of active hemorrhage. Anti-XA level was 0.51 IU/mL. Heparin drip was discontinued, and the patient was transferred to the intensive care unit (ICU) where he was treated conservatively with fluid resuscitation and blood transfusions as needed for a goal of hemoglobin more than 7 g/dL.
The patient’s hemoglobin was stable throughout the days after ICU admission, and he did not require any more transfusions of packed red blood cells. His respiratory status was steady despite the discontinuation of anticoagulation with heparin. He was discharged without anticoagulation therapy due to a high risk for rebleeding. |
pmc-6497686-1 | A 73-year-old man underwent right lower lobectomy with lymph node dissection (ND2a-2) for right primary lung cancer (cT1cN2M0 Stage IIIA). Because the patient was complicated with idiopathic pulmonary fibrosis with emphysema (CPFE), we performed surgery without preoperative chemoradiotherapy in consideration of the risk of acute exacerbation of interstitial pneumonia. The lobar bronchus was closed by stapler, and suture closure was performed with a pericardial fat pad graft covering the bronchial stump to prevent the development of a BPF. Overall, his postoperative course was unremarkable; however, on postoperative day (POD) 13, computed tomography (CT) revealed pneumonia of the right middle lung lobe, and antibiotic therapy was initiated. However, he was refractory to the antibiotic therapy, and repeat CT (on POD 20) revealed air retention around the bronchial stump (Fig. a). Bronchoscopy showed the formation of a fistula involving the bronchial stump at the right lower lobe (Fig. b), and he was diagnosed with a BPF. We performed emergency fenestration to control bacterial infection and avoid a life-threatening situation. Since rehabilitation was not progressed due to postoperative pain and CPFE, we decided to perform fenestration using a Lap protector to avoid extensive surgery and continue postoperative rehabilitation. Intraoperatively, we made a skin incision (6 cm in length) in the eighth intercostal space in the posterior axillary line just above the thoracic cavity and incised the subcutaneous tissue and the muscles of the chest wall. We separated the intercostal muscles and inserted a Lap-protector (FF0707, Hakko Co., Ltd, Japan) (Fig. a). The thoracic cavity was thoroughly irrigated, and the fistula was confirmed cranial to the pericardial fat pad graft covering the bronchial stump. Postoperatively, the daily application of gauze dressings was continued without any complications such as pneumonia, and the fenestration wound showed good healing compared with the immediate postoperative wound (Fig. b), his routine activities were unaffected postoperatively. Although complete closure of the fistula did not occur by the time of his 1-year postoperative follow-up (Fig. c, d), the bacterial infection was well-controlled and chest CT showed a prominent reduction of the thoracic cavity (Fig. a–d), we planned to cover the bronchial stump and to fill the thoracic cavity by omentum. However, as the rapid deterioration of the general condition due to the recurrence of the tumor was observed, closing of the thoracic cavity was abandoned, and now, symptomatic treatment is performed under the daily application of gauze dressings. |
pmc-6497696-1 | A 74-year-old man had undergone left lower lobectomy for NSCLC (Fig. ). The tumor was pathologically diagnosed as squamous cell carcinoma of the lung (1.9 cm in size) without lymph node metastasis (TNM classification 7th edition, pT1aN0M0 and stage IB) (Fig. ). He was followed up periodically, and a computed tomography (CT) scan that was taken 1 year after the operation revealed an 8.3 cm, irregularly shaped mass lesion in segment five of the liver (Fig. ). Retrospectively, CT performed 6 months prior showed a 3.1 × 2.9 cm low-density lesion at the identical site (Fig. ). Since 18-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography and enhanced brain magnetic resonance imaging (MRI) ruled out any metastatic lesions other than the one in the liver, the patient was referred to a gastroenterological surgeon. Liver MRI demonstrated a well-defined mass, which was hypointense relative to the liver parenchyma on T1-weighted images (Fig. ) and hyperintense on T2-weighted images (Fig. ). The hepatic mass exhibited clear hypointensity in the late dynamic and hepatobiliary phases on ethoxybenzyl diethylenetriaminepentaacetic acid-MRI (Fig. ). Moreover, MRI showed that the mass had increased to 9.6 cm in diameter within a 1-month interval. Although serum levels of carcinoembryonic antigen (CEA; cut-off value, 3.4 ng/ml) and cytokeratin 19 fragment (CYFRA; cut-off value, 3.5 ng/ml) were both within the normal range at the time of lung resection, both CEA and CYFRA levels increased to 11.0 ng/ml and 23.0 ng/ml, respectively, along with enlargement of the hepatic mass (CEA and CYFRA levels at each time point are indicated in Figs. and ).
Since his general condition was good and his major organ functions were tolerable to general anesthesia, the patient underwent right hepatectomy 14 months after the lung resection at the primary site. Intraoperatively, a huge mass was detected in the right liver, but no other metastatic sites were identified. The postoperative course was uneventful, and the patient was discharged on postoperative day 10.
The macroscopic examination of the cut specimen showed an irregular, grayish mass that measured 10 × 8 × 5.5 cm, with massive central necrosis (Fig. ). The pathologic examination confirmed metastatic squamous cell carcinoma of the lung (Fig. ). He did not receive adjuvant chemotherapy and was free from recurrence 41 months after the hepatectomy. |
pmc-6498249-1 | A 66-year-old female, gravida 1, para 1, presented to our gynecologic unit with complaints of right lower abdominal pain. Magnetic resonance imaging (MRI) showed a bilocular 8 cm tumor with thick wall posterior to the uterus and demonstrated bleeding or mucinous component (Fig. i). A serum CEA level increased to 8.8 ng/ml (normal range 0.0–5.0 ng/ml). 2 months later, a size of the tumor was the same, and a serum CEA level was 8.4 ng/ml. We scheduled the gynecologic examination 1 year later, because she strongly hoped long interval of follow-up, but she did not show up and lost to follow-up.
6 years later, she presented to our hospital again, because elevated level of CEA (19.0 ng/ml) was found at other hospital. Gastroscopy and colonoscopy, which were performed at the previous hospital, revealed no abnormal findings. Her past medical history was unremarkable. Bimanual pelvic examination demonstrated a normal-sized uterus and cervix as well as a fist-sized cystic mass at Douglas cavum. The cervical cytology was negative. Transvaginal ultrasound identifies 8.5 × 6.0 × 5.0 cm cystic tumor with partial thick wall posterior to the uterus. MRI showed a 9 × 6 cm pelvic tumor, including partial papillary nodules with contrast enhancement and little amount of ascites (Fig. ii). The initial level of the serum CEA was 34.9 ng/ml.
A clinical impression of ovarian neoplasm, with suspicion of mucinous tumor of low malignant potential, was made and the patient underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. We recognized goose egg-sized left adnexal tumor, normal-sized uterus and right adnexae, the normal vermiform appendix, and no ascites during the surgery. Postoperative recovery was uncomplicated. The cytology of ascites was negative. The level of serum CEA decreased to normal (4.0 ng/ml) after the surgery. The patient received no further treatment and remains free of disease for 1.5 years.
We described the macroscopic findings below. The surgical specimen consisted of a 9.5 × 6.5 × 4.0 cm—sized left ovarian tumor, normal uterus, and right adnexae. The external surface of the tumor was smooth, and not disrupted. The cut section revealed partial thick wall, yellow gelatinous component and a few hairs within the tumor, but a solid part did not exist (Fig. ).
On microscopic examination, sections from the cyst wall disclosed a mature cystic teratoma and contained mature tissue of stratified squamous epithelium, mucinous gland, and adipose tissue. The wall (in the circular marks of Fig. c) consisted of four-layer structure, which was mucosa, muscularis mucosa, submucosal, and muscularis propria. The mucosal cells were positive for PAS-Alcian blue stains, and the cells of muscularis mucosa and muscularis propria were positive for desmin stains. The cells showed highly dense, pseudostratified and disturbed nucleus, but mitosis was limited and there were no atypia and infiltration. They were positive for cytokeratin (CK) 20 and CDX (caudal-type homeobox transcription factor)-2, and negative for CK7 and p53 by immunohistochemistry stains, which corresponded with the features of intestinal epithelium (Fig. ). The histopathological diagnosis was a mature cystic teratoma with intestinal structures harboring intestinal-type low-grade mucinous neoplasm of the left ovary, mimicking mucinous cystadenoma of appendix. |
pmc-6498274-1 | A 68-year-old female was referred to the emergency department of our hospital in April 2016. She was suffering from anorexia, abdominal distension, abdominal pain in lower-right abdomen. Furthermore, a right-side inguinal hernia and uterine prolapse were revealed by a physical examination. Her height and weight were 154 cm and 65 kg, respectively, and she had no history of other diseases.
Laboratory data showed inflammatory changes, as indicated by a white blood cell count of 13,600/μl, CRP of 33.8 mg/dl, hypoalbuminemia at the serum albumin level 3.4 g/dl, and slight renal dysfunction (BUN 108 mg/dl, Creatinine 4.25 mg/dl); in addition, she had elevated levels of tumor markers CEA, CA19-9 and CA125 at 37 ng/ml, 113 U/ml, and 124 U/ml, respectively.
Abdominal computed tomography (CT) at admission revealed massive ascites and a cystic mass in the lower-right abdomen that ruptured to abdominal cavity (Fig. a). The CT density of the ascites was 10–20 Hounsfield units (H.U.) which was higher than serous ascites (0–5 H.U.) CT also revealed a right inguinal hernia containing the small intestine (Fig. b) and uterine prolapse (Fig. c). Magnetic resonance imaging revealed that the cystic tumor was arising from appendix (Fig. ). We had aspirated the ascites being yellow and cloudy. And cytology of the ascites showed mucus suggesting the diagnosis of PMP but no malignant cells (Fig. ).
Based on these findings, we diagnosed the patient with ruptured appendiceal mucinous adenoma and PMP and scheduled a laparotomy. Massive yellow and cloudy ascites and ruptured cystic tumor arising from the appendix were seen (Fig. a). Bilateral ovaries and peritoneum were covered with the yellow substance. We performed an appendectomy containing the cystic mass, bilateral oophorectomy and a biopsy for the peritoneum. We irrigated the abdominal cavity using 3000 ml of dextran solution.
Additionally, we fixed the pelvic diaphragm by sutures and repaired the inguinal hernia via the another incision.
The macroscopic findings showed a ruptured cystic mass measuring 5 × 4 cm arising from the middle of the appendix. We also noted small nodules inside the capsule. Mucous was retained in the vermis. The bilateral ovaries and peritoneum were also covered with yellow mucin. The pathologic findings revealed the presence of low-grade atypical cell inside the capsule, and fibrosis with hemosiderin and cholesterin was observed in the wall of the vermis (Fig. ) . However, no tumor cells were found on the surface of the ovary or peritoneum.
The postoperative course was uneventful, and the serum tumor marker levels subsequently decreased to CEA 3.1 ng/ml, CA19-9 47.6 U/ml, and CA125 17.7 U/ml, 2 months later.
We administered S1 (75 mg/body for 14 days every 21 days) to prevent the relapse. The patient is doing well in 1 year later. |
pmc-6498278-1 | A 70-year-old woman with active rheumatoid arthritis, who was under treatment with salazosulfapyridine 1,000 mg/day, was diagnosed as having BRAF wild-type primary mucosal melanoma. The melanoma was resected, and 60-Gy/30-Fr radiotherapy was administered as the adjuvant treatment. One year after the initial presentation, relapse occurred in the left sixth rib and left iliac fossa. Duodenal metastasis was also observed, wherein ulceration with gastrointestinal bleeding was identified. The patient had anemia and required transfusion at least three times per week. The patient received the first treatment session with nivolumab (2 mg/kg); no substantial adverse effect was observed. After 19 days, her rib tumor started to decrease in size. After 26 days, the tumor could not be visualized on chest radiography (Fig. ) and no substantial adverse effects were observed. Computed tomography (CT) performed 1 month after therapy initiation showed the absence of the costal lesion and an acceptable reduction of more than 60 % of the ileal lesion (Fig. a). The ulcerated duodenal lesion on the endoscopy performed 4 months after the treatment showed cicatrization (Fig. b). Anemia due to bleeding from the tumor was reduced after the second week, and blood transfusion was discontinued (Fig. a, b).
During the four courses of nivolumab treatment, slight changes of the laboratory data were observed, however, there were no adverse events, and the joint pain and DAS28ESR scores did not get worse (Fig ; Table ). After receiving six courses of nivolumab therapy, she maintained a complete response for 9 months, without rheumatic exacerbation or drug-related adverse events. |
pmc-6498281-1 | Eleven years ago, when our patient was a 33-year-old unmarried nulligravida, she developed CCC of the ovary for the first time. At that time, her menstrual cycle was regular and 30 days long, with dysmenorrhea, manifesting as lower abdominal and lumbar pain, persisting for 5–7 days. There was no family or medical history of note. She had visited a local clinic with the chief complaint of lumbar pain, where a right ovarian tumor 8 cm in size that included solid internal components, was identified, and she was referred to the University of Tsukuba Hospital. Transvaginal ultrasound had revealed a right adnexal mass with solid components, 68 mm × 53 mm in size, and an intramural uterine fibroid 23 mm × 27 mm, with no hypertrophy of the endometrium, which measured 2.1 mm. Blood counts and blood biochemistry test results revealed no abnormalities. Her serum CA19-9 level was 45.9 U/ml, CA125 was 22 U/ml, and CEA level was 1.3 ng/ml. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) revealed an 80-mm unilocular cystic mass in the right ovary with a papillary protrusion of longest diameter 45 mm. The left ovary was not enlarged, and there was no obvious peritoneal dissemination or enlarged lymph nodes. Surgery, comprising right adnexectomy, left ovarian biopsy, partial omentectomy and uterine fibroid removal, was performed. The right ovary was enlarged to 8 cm in size, and it was removed without intraoperative rupture and with its capsule intact. The left ovary was not enlarged, but was seen to have a small endometrial cyst, which was resected. The absence of peritoneal dissemination and enlarged lymph nodes was confirmed during surgery. The pathological diagnosis was CCC localized to the right ovary and endometriosis was observed in the left ovary, with ascites cytology Class III. The cytology was composed of clusters that include atypical cells having somewhat nuclear enlargement, and it makes a diagnosis difficult to distinguish mesothelial cells from malignant cells. The patient expressed a strong desire to preserve her fertility. Hence, pelvic and para-aortic lymph node dissections were performed via staged laparotomy, which revealed no metastases in any of the 91 pelvic or para-aortic lymph nodes that were removed, leading to a diagnosis of Stage IA CCC. Four courses of postoperative combination paclitaxel (175 mg/m2) and carboplatin (AUC6) chemotherapy (TC therapy) were administered to complete the initial treatment.
Nine years after the initial therapy, MRI during regular 6-monthly monitoring revealed the appearance of a 95-mm polycystic mass with a mural nodule of longest diameter 53 mm in the left adnexal region. Those findings were never seen at the previous MRI. At this time, her serum CA19-9 level was 12.9 U/ml, CA125 was 18.3 U/ml, and CEA level was 0.5 ng/ml, all of which were within normal limits. Disease recurrence in the contralateral ovary was diagnosed, and total abdominal hysterectomy, left adnexectomy and omental biopsy were performed. At the time of surgery, the left ovary was enlarged to 95 mm in size, and it was removed intact without intraoperative rupture of its capsule. The internal lumen of the tumor contained several milky-white mural nodules extending around 15 mm into the cavity (Fig. ). The histological diagnosis was CCC, but in addition to the possibility of recurrence, it was also considered that the tumor might have developed de novo, and the fact that clear cell adenofibroma (CCAF) was also present (Fig. ) suggested that this might have provided the genesis for its development. In addition, there were no endometriotic lesions in the non-solid cyst wall, and it only consists of fibrous membrane. The tumor was localized to the left ovary, and since ascites cytology was negative, it was diagnosed as Stage IA disease. The treatment was completed with four courses of postoperative TC therapy.
Two years after the completion of treatment, the patient is continuing outpatient monitoring with no sign of recurrence to date. |
pmc-6498289-1 | In June 2009, a 73-year-old man was referred to our hospital presenting with left RCC measuring 6.0 × 5.6 cm with multiple lung metastases (Fig. a–f). The patient had a history of diabetes mellitus and allergy to iodine-containing contrast medium. At his previous clinic, he had been given a transbronchial lung biopsy and diagnosed with clear cell RCC metastatic to the lung. At our hospital, thoracoabdominal CT scan and bone scintigraphy showed no other visceral or lymph-node metastases, and the patient was diagnosed with clear cell RCC with cT1bN0M1 staging. He received sunitinib as the first-line systemic therapy for metastatic clear cell RCC. Eight months later, the primary renal tumor was reduced to 5.5 × 4.8 cm. In addition, the volume of the metastatic sites was also reduced (the maximum nodule decreased from 1.5 × 1.3 to 1.0 × 0.8 cm). Because we could confirm the responses of medical therapy and the patient had a good performance status, cytoreductive nephrectomy was performed in May 2010. The pathological investigation revealed well-defined (G1-2) clear cell RCC measuring 4.5 × 4.0 × 2.0 cm in the upper pole of the left kidney, which had a negative margin and negative lymphovascular invasion. Eosinophilic amorphous materials, which was a degenerative effect of the previous therapy, were found in the tumor. After nephrectomy, the patient received interferon-alpha cytokine therapy for 13 months because his metastatic sites were limited to lung. However, his lung metastases continued to grow gradually during this treatment, targeted therapy with sunitinib was re-introduced. Between June 2011 and January 2016, he underwent sequential targeted therapy consisting of sunitinib, everolimus, and axitinib for 21, 11, and 23 months, respectively. In October 2015, a follow-up CT scan disclosed a mass measuring 2.2 × 1.6 cm in the stomach (Fig. a). The patient had experienced no symptoms associated with the gastric mass. Upper gastrointestinal endoscopy revealed a solitary, distinct polypoid lesion (2 cm in diameter) classifiable as a 0-I tumor according to the Japanese Classification of Gastric Carcinoma (14th edition) [] at the fundus of the stomach (Fig. b). Tumor biopsy was performed and microscopic examination confirmed that this lesion was a metastasis from RCC. In February 2016, the patient underwent endoscopic mucosal resection of the gastric metastatic lesion. Histological evaluation of the resected specimen (3 cm in diameter) demonstrated well-defined clear cell RCC histology (G1 > G2) with submucosal invasive depth, positive vertical margin, and negative lymphovascular invasion. The patient’s therapy was switched to immunotherapy with the anti-programmed cell death 1 antibody nivolumab (2 mg/kg every 3 weeks). Six months after initiation of the immunotherapy, follow-up CT scan showed that the lung metastases had diminished remarkably and no new additional metastasis was found. Regarding the gastric lesion, follow-up endoscopy and endoscopic ultrasonography were performed 1 month after resection. There were no residual tumors although there were positive margins. Thereafter, these endoscopic examinations were performed every 6 months. To date, there has been no recurrence despite the positive surgical margin. |
pmc-6498291-1 | A 56-year-old woman visited our hospital presenting a left adrenal tumor; during examination, a spleen nodule was incidentally diagnosed. Computed tomography revealed a 7.4-cm-long enhanced left adrenal tumor and 1.8-cm-long enhanced nodule within the spleen (Fig. ). Lymph node and other organ metastases were absent, and adrenal endocrine examination findings (serum cortisol, renin, aldosterone, testosterone, metanephrine, DHEA-S, and 17-OH progesterone) were within the normal ranges. Open left adrenalectomy and splenectomy were simultaneously performed, and the adrenal tumor and spleen were separated from each other; notably, the perioperative findings demonstrated no direct invasion. As per gross examination, the adrenal tumor was reddish-brown and covered with multiple white capsula fibrosa. The cut surface of the spleen nodular tumor was also reddish-brown. The pathological findings of the adrenal tumor demonstrated the presence of epithelioid cells with eosinophilic cytoplasm; some tumor cells were found within the blood vessels (Fig. a). The spleen tumor also demonstrated round epithelioid cells with eosinophilic cytoplasm and large hyperchromatic nuclei with prominent nucleoli (Fig. b). Immunohistochemical analysis revealed that the adrenal and spleen tumors were positive for CD31, CD34, and factor VIII. The final pathological diagnosis was angiosarcomas with a simultaneous occurrence in the spleen and left adrenal gland. The patient was alive and in remission at postoperative 18 months. |
pmc-6498321-1 | A 64-year-old man with a history of hypertension was referred to our hospital with a high serum level of prostate-specific antigen (9.01 ng/ml). The patient had no medical history of immune disease such as inflammatory disease, arthritis or hematological disease. The result of a systemic prostate biopsy showed prostate cancer with a Gleason score of 7, and a clinical stage of cT2bN0M0. The patient underwent a retropubic radical prostatectomy. We treated the patient with ampicillin sulbactam for prevention of post-operative infection. The site of the surgical wound and drain insertion presented redness and produced pus in addition to prolonged fever for 4 days following surgery. Following the diagnosis of surgical site infection, antimicrobial therapy using meropenem that is a broad-spectrum antibacterial agent of the carbapenem family was initiated (Fig. a). Although the patient received appropriate debridement and broad-spectrum antibiotic treatment, the ulcerative lesion spread surrounding drain region and the condition of the skin region deteriorated 10 days following surgery. The patient presented kidney and liver dysfunction and was transferred to the Intensive Care Unit. Despite treatment with an additional antifungal agent and debridement, there was no improvement (Fig. b). Blood, urine, sputum and wound culture were negative for any pathogen. The diagnosis of PG was made by a skin biopsy that presented only neutrophilic invasion in the dermis without vasculitis, tumor, or malignancy 37 days following surgery (Fig. ). Although treatment with 80 mg/day intravenous prednisolone was initiated, the patient died of multiple organic dysfunction due to liver, heart, and kidney dysfunction. |
pmc-6498346-1 | A 50-year-old female who had never smoked presented with a cough for 4 months and dyspnea for 3 weeks. Chest computed tomography (CT) scans revealed a lung mass in the left upper lobe, multiple nodules in both lungs, and several hilar and mediastinal lymphadenopathy. The patient was diagnosed with poorly differentiated stage IV lung adenocarcinoma (clinical T4N3M1b), which was ALK-positive by immunostaining with ALK antibody. Fluorescence in situ hybridization (FISH) analysis for ALK gene rearrangement was inconclusive. Brain MRI revealed asymptomatic multiple parenchymal metastases. First-line chemotherapy with carboplatin/paclitaxel/bevacizumab was administered, resulting in stable disease after 4 cycles. Despite an improvement in systemic disease, brain MRI after 3 months demonstrated tumor enlargement. The patient underwent gamma knife radiosurgery against multiple brain metastases and second-line chemotherapy with crizotinib was initiated. After 4 months of crizotinib treatment, partial responses were detected in the primary tumor site, and intrapulmonary and lymph node metastases, but brain MRI indicated that leptomeningeal carcinomatosis had developed. The patient received whole brain radiotherapy (WBRT), after which she experienced sharp pains in the arms and neck. T1 brain MRI revealed no change in leptomeningeal carcinomatosis (Fig. a), whereas T1 neck MRI led to the detection of new metastases in the cervical spinal cord (Fig. a). Because of the wide distribution of spinal cord metastases, radiation therapy was contraindicated. To manage the CNS metastases, including those in the leptomeninges and spinal cord, third-line chemotherapy with alectinib (600 mg/day) was initiated. The patient reported a gradual improvement in arm and neck pain. After 3 months of alectinib treatment, T1 MRI demonstrated a marked reduction in leptomeningeal carcinomatosis (Fig. b) and spinal cord metastases (Fig. b). Alectinib was well tolerated, with no significant adverse events. |
pmc-6498359-1 | A 68-year-old woman presented to our department with abnormal vaginal bleeding. Her family history was not contributory, and she had no previous medical history. Transvaginal ultrasonography revealed a tumor in the uterine cavity. On endometrial biopsy, the papillary growth of tumor cells was observed. On magnetic resonance imaging (MRI), T2-weighted images showed thickening of the endometrium and contrast enhancement (Fig. ). On computed tomography (CT) images, no distant metastasis was observed. Transabdominal simple hysterectomy, bilateral adnexectomy, and pelvic lymphadenectomy were performed. The resected tumor filled the uterine cavity with papillary excrescence and its size was 60 mm (Fig. a). Histopathological examination demonstrated a papillary architecture with the papillae comprising broad fibrovascular cores and cancer had spread into the inner half of the myometrium (Fig. b, c). However, there were adnexal and perimetrium metastases. Based on these findings, a diagnosis of stage IIIA (pT3aN0M0) ESC was made. As postoperative adjuvant therapy, combination chemotherapy of paclitaxel and carboplatin (TC) was administered. Before the second cycle, the regimen was changed to docetaxel and cisplatin (DP) because of skin eruptions induced by paclitaxel or carboplatin. Four cycles of DP were administered. After 5 months, CT revealed tumors in the vaginal wall and left internal iliac lymph node. As fluorodeoxyglucose positron emission tomography (FDG-PET) showed accumulation with maximum standardized uptake values (SUVmax) of 15.4 in the vaginal wall and 5.1 in the left internal iliac lymph node, the first recurrence of ESC was diagnosed (Fig. a, b). Concurrent chemoradiotherapy (CCRT) was performed. Chemotherapy comprised nedaplatin and docetaxel (nedaplatin 20 mg/body plus docetaxel 20 mg/body, on day two, every week for three cycles). Concurrent radiotherapy of 66 Gy (22 fractions of 3 Gy, 5 days/week) was delivered over 5 weeks using intensity modulated radiation therapy (IMRT) (Fig. a, b). The planning target volume (PTV) was the clinical target volume (CTV) + a 5-mm margin. Tumor regression was observed and the uptake in the recurrent site decreased considerably on the FDG-PET scan. After 4 months, the second recurrence was detected in the right internal iliac lymph node using FDG-PET with an SUVmax of 13.8. CCRT was performed again (Fig. a). The PTV was also the same. Tumor regression was observed and the uptake in the recurrent site decreased considerably on the FDG-PET scan. After 4 months, the third recurrence was detected in the right common iliac node using FDG-PET with an SUVmax of 9.0. CCRT was performed once more (Fig. b). The PTV again was the same. Tumor regression was observed and the uptake in the recurrent site decreased considerably on the FDG-PET. After 8 months, the fourth recurrence was detected in the horizontal portion of the duodenum using FDG-PET with an SUVmax of 8.6. IMRT (50 Gy in 25 fractions) was performed (Fig. c). The PTV was the same. The tumor regression was observed and the uptake in the recurrent site decreased considerably on the FDG-PET scan. After 9 months, small tumor induration was palpable on vaginal and rectal examinations. The fifth recurrence was detected in the vaginal wall, via vaginal tumor biopsy. Histological examination revealed papillary tumor cells, which were identical to those of the primary uterine lesion, with necrosis, and FDG-PET showed accumulation with an SUVmax of 4.2 in this site. Interstitial brachytherapy (48 Gy in 8 fractions) was performed. Tumor regression was observed and the uptake in the recurrent site decreased considerably on the FDG-PET. Grade 2 gastrointestinal fistula, nausea and radiodermatitis (CTCAE; Common Toxicity Criteria for Adverse Events, version 4.03) were observed during the treatment. During the subsequent 13-month follow-up, there has been no recurrence. |
pmc-6498377-1 | A 45-year-old Japanese man receiving HIV infection treatment had gross hematuria. Since the ultrasound sonogram and computed tomography (CT) scan showed a left ureteral tumor (Fig. a), he was presented to our department for further examination and treatment. His medical history included condylomata acuminate of the penis, hepatitis B, and HIV infection. The HIV infection was well controlled with dolutegravir and emtricitabine/tenofovir. He had no significant family, allergic, or smoking history. He received no blood transfusions. Serum laboratory findings showed an increased creatinine level (1.23 mg/dL; normal range <1.2 mg/dL) but no increase in tumor markers such as the squamous cell carcinoma antigen and cancer antigen 19-9. Results of urinalysis showed hematopyuria, and urine cytology findings were pseudo-positive for urothelial carcinoma, of which few cells had a high nuclear-cytoplasmic ratio and their nuclei were hyperchromatic. On cystoscopy, no bladder tumor was observed. A whole-body CT scan was performed, and no distant metastasis or lymph node involvement was found. We also conducted retrograde unilateral left pyelography and a selective upper urinary cytology examination. The pyelogram showed the same left ureteral mass that was found on the CT scan. Results of the left upper urinary cytology examination were negative; there were few atypical cells, but their nuclei were not hyperchromatic. We diagnosed the ureteral tumor as a urothelial carcinoma (cT2N0M0) because of the left ureteral tumor and abnormal urine cytology findings, and laparoscopic ureteronephrectomy was performed. Macroscopically, a solid, papillary tumor, 30 mm in diameter, was observed in the upper side of the ureter (Fig. b). Histopathological findings included plasmacytoma-like atypical cells with a high nuclear-cytoplasmic ratio, perinuclear halo formation of invasion at the periureteral soft tissue of the ureter (Fig. a, b), and lymphocytic and histiocytic infiltration in the tumor. Invasion of the tumor cells was not observed in the pelvic mucosa or renal parenchyma. There was no component of urothelial carcinoma in the tumor or surrounding mucosa of the ureter. Immunohistochemical staining was performed to confirm the definitive diagnosis. Tumor cells were negative for cytokeratin (CK) 7, CK20, and p63 but positive for the markers of B cells or plasma cells, such as CD138 and CD79a/mb-1 (Fig. c). In addition, light chain restriction [immunoglobulin (Ig)γ > Igκ] was observed (Fig. d). The final histopathological diagnosis was plasmacytoma not urothelial carcinoma.
Postoperatively, the patient recovered without any complications. It was necessary to explore the entire body to find any other plasmacytomas. The positron emission tomography scan showed no other lesions. Bone marrow aspiration findings were normal, and radiographs of the skull, spine, limbs, and pelvis showed no osteolytic lesions. High levels of monoclonal protein were not found in the blood or urine. Finally, the definitive diagnosis was solitary extramedullary plasmacytoma of the ureter (Durie and Salmon criteria, stage 1). He is alive and free of disease at 7 months postoperatively. |
pmc-6498383-1 | An 80-year-old man was admitted to our hospital for the treatment of a rectal tumor found incidentally by rectal examination. The tumor, about 3 cm in diameter, was located on the right side of the lower rectum 3 cm above the anal verge. The pathological analysis of the biopsy sample revealed that the tumor was a moderately differentiated adenocarcinoma. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) indicated that the rectal cancer invaded into the muscularis propria without distant metastases and that lateral pelvic lymph node (LPLN) was not enlarged with a maximum long-axis diameter <3 mm. The most important problem was that the patient had a huge benign prostatic hypertrophy, the size of which was 85 × 80 × 70 mm (Fig. a–c). To achieve complete TME with negative CRM, a hybrid transabdominal-transanal approach for ISR was conducted.
First, vascular division and mobilization of the left colon were performed laparoscopically. The transabdominal approach was continued until the anterior dissection of the rectum became difficult due to a huge prostatic hypertrophy. Next, the circumferential rectal incision and subsequent intersphincteric dissection were performed under direct vision to enable attachment of a single port device (GelPoint Mini; Applied Medical). After closure of the anal orifice, the GelPoint Mini was placed to start the transanal approach. Posterior side of the rectum was first dissected until the transanal approach was connected to the dissection layer made by the transabdominal approach. The dissection procedure was extended to the lateral side. Bilateral pelvic splanchnic nerves were identified at the 5 and 7 o’clock positions. At the anterior side, the proper dissection layer cannot be easily identified because of the perineal body and the enlarged prostate. Once the dissection plane between the rectum and the prostate could be identified, it was relatively easy to continue along the same plane. The assistance provided by the laparoscopic approach was useful to determine the appropriate dissection line in the transanal approach. |
pmc-6498463-1 | A 65-year-old man suffered from chest tightness was admitted to our center seven months ago. Echography results demonstrated severe aortic and mitral valve regurgitation. He was treated with open cardiac aortic valve replacement (biological valve, 25#, Edwards) and mitral valve repair. During the sixth-month follow-up after cardiac procedure, chest radiographs revealed suspected intimal patches of aortic arch and descending aorta, further, thoracic aortic angiography showed aortic dissecting aneurysm (Fig. ). The site of dissection was about 4 cm above the coronary ostium, where the aortic cannula placed, indicating that it might be caused by inappropriate string technique in surgery. The patient was presented with no chest pain, tightness, syncope, nausea or vomiting. After conservative medical treatment for one month, he came to our department and received endovascular stent-graft implantation and in situ laser fenestration for revascularization of aortic arch.
Femoral vein-bilateral carotid bypass was established by femoral vein (20 F catheter sheath) and bilateral carotid (12–16 F catheter sheath) cannulation. The stent release system (40–40*200 mm, Gore, USA) was introduced. The anchorage area was located 1 cm above the coronary artery orifice, and the stent was released after the systolic blood pressure was reduced to 90 mmHg. The laser catheter was introduced through the left carotid artery, directly contacting the endograft membrane as perpendicularly as possible. Fenestration was made by applying 0 5 J energy (holmium laser, frequency: 5 Hz.), followed by 4-mm balloon dilation. Then, a 0.035-in. stiff guidewire was selected and advanced into the endograft lumen to introduce a bare stent (10 × 38 mm2).The same procedure was performed for the left carotid artery and left subclavian artery (Fig. ). The operation was completed within 4 h, and the time of extracorporeal circulation was 56 min. The patient recovered without any clinical complications and was discharged five days after the procedure. |
pmc-6498505-1 | An 81-year-old female (Proband, patient II-6) had rectal cancer (at 47 years of age), sigmoid cancer (at 54 years of age), endometrial cancer (at 59 years of age) and rectal cancer (at 81 years of age). Her son (patient III-14) had A-colon cancer (at 46 years of age). Her daughter (patient III-15) had endometrial cancer (at 50 years of age). Her three sisters had A-colon cancer (at 33 years of age, patient II-2) and was deceased (at 37 years of age), T-colon cancer (at 47 years of age, patient II-3) and was deceased (at 49 years of age) and A-colon cancer (at 34 years of age, patient II-8) and was deceased (at 35 years of age). Her brother had caecal cancer (at 35 years of age, patient II-7) and was deceased (at 47 years of age). Her father had T-colon cancer (at 60 years of age, patient I-1) and was deceased (at 64 years of age). Her sister’s daughter had breast cancer (at 33 years of age, patient III-4) (Fig. ). MLPA analysis was performed in patients who were referred to genetic counselling clinics at the Hoshi General Hospital. Heparinized peripheral blood lymphocytes were collected from the proband and her daughter and analysed for large genomic disorganization of the MLH1 gene. The protocol was approved by the Ethical Review Board of the Hoshi General Hospital and conformed to the ethical guidelines on human genome studies. Additional informed consent was obtained from all individual participants for whom identifying information was included in this article. According to the genetic screening and test, the approval of the Ethical Review Board was obtained in all families. |
pmc-6498571-1 | Here, we report a unique case of a 76-year old female patient with FCED who underwent DMEK surgery. Several years before, the patient’s spleen had to be removed because of an iatrogenic splenic injury during laparoscopy. The patient was generally immunocompetent and not unusually susceptible to infections. DMEK surgery without HLA-matching was performed without complications. Postoperatively, the patient received topical corticosteroids (prednisolone acetate 1% 5 times daily), which was slowly tapered and stopped after 2 years, antibiotics (Ofloxacin 3 times daily for 2 weeks) and lubricants. The patient was followed regularly by slit-lamp biomicroscopy and visual acuity and endothelial cell densities were determined. During follow-up, we did not detect any signs of allograft rejection. Visual acuity was 20/25 at 3 months and 20/20 at 1, 3, and 4 years postoperatively. Donor endothelial cell density was 2553 cells/mm2 preoperatively, 1779 cells/mm2 at 3 months, 1609 cells/mm2 at 1 year, 1377 cells/mm2 at 3 years, and 1274 cells/mm2 at 4 years postoperatively. Thus, endothelial cell loss rates were comparable to rates reported for eyes without rejection []. |
pmc-6498597-1 | A 35-year-old Dinka woman from South Sudan presented with left-sided facial asymmetry associated with numbness on the left side of her body and deteriorating vision in her left eye. Her symptoms started 5 years earlier with slowly progressive left-sided facial atrophy associated with reduced vision in her left eye and early morning blurred vision. Two years later she started feeling numbness on the left side of her body (upper limb and lower limb spontaneously). Numbness and atrophy became static in the last year with further deterioration in vision.
She never had any seizures or history of a psychiatric illness. There was no family history of a similar condition; she was not on any medication or known to have any chronic illness.
On examination, there was noticeable left-sided facial atrophy extending from the frontal bone to mental region associated with enophthalmos affecting her left eye, minimal tongue atrophy on the same side, and clear coup de sabre in her left cheek (Fig. ). An intraoral examination revealed minimal tongue atrophy on the left side, badly decayed right maxillary third molar together with the mandibular second and third molars, and there were caries on left mandibular and maxillary third molars.
Her cranial nerves were intact, however, there was decreased sensation (fine touch and pin prick) affecting the left side of her body (including the left side of her face), although tone, reflexes, and proprioception were all intact. An examination of her right side was unremarkable. An ophthalmic examination showed a left eye visual acuity (VA) of 6/40, keratic precipitates, immature cataract, raised intraocular pressure (IOP) of 26, and hazy fundoscopy; however, she had a normal right eye with VA of 6/6 and IOP of 12.2. A brightness scan (B-scan) was performed and it was normal in both eyes (Fig. ). Other systemic examinations of her heart, chest, and abdomen were unremarkable.
A diagnosis of PRS with overlapped linear scleroderma was postulated and further radiologic and laboratory assessments were made.
General routine investigations revealed normocytic normochromic anemia probably due to amoebiasis infection found in her stool sample (no other agents were seen such as ova or worms) which was corrected after treatment. Liver and renal function tests were within normal ranges as was her vitamin B12 level. Furthermore, rheumatoid factor was positive yet antinuclear antibody (ANA) profile and anti-cyclic citrullinated peptide (CCP) tests were all negative. Laboratory results are shown in Table .
Radiological imaging with computed tomography (CT) scan of her facial bones revealed mild asymmetry of her face with early affection of the left zygomatic bone. There was obvious atrophy involving left-sided facial subcutaneous tissue extending to the masseter muscle (Fig. ). Moreover, an orthopantomogram (OPG) showed multilocular radiolucency at the left angle of her mandible with remaining roots in the left mandibular third molar, decay in the maxillary left third molar (appeared as radiolucency in the enamel and dentine occlusally), an unerupted right maxillary third molar, and badly decayed mandibular third molar teeth (Fig. ).
An electroencephalogram (EEG) revealed normal study: normal 9 Hz, α-rhythm in awake EEG with no epileptiform activity seen.
Two skin biopsies were requested that reported: skin with hyperkeratosis, follicular plugging, thin stratum Malpighii, and focal vacuolar degeneration of the basal layer with presence of dermal thick collagen fibers and mononuclear inflammatory cellular infiltration. This picture was consistent with linear scleroderma overlapping PRS. |
pmc-6498611-1 | Girl M. 4 years old, entered the clinic with complaints of parents for growth retardation, pain in the lower limbs and stiff joints. The genealogy analysis found that the marriage was unrelated, parents were young and healthy, the girl was the only child in the family.
The girl was from the first pregnancy, complicated by an acute respiratory viral infection in the first trimester. The birth was at 40 weeks of pregnancy. Body weight at birth was 3170.0 g, body length was 52 cm. Early motor development proceeded with a slight delay: she began to support the head at the age of 2.5 months, sit at 9 months, and walk at 15 months. The first words began to be pronounced at the age of 12 months.
At the age of 18 months, there were complaints about the short stature of the child, stiffness of the joints. After analyzing the karyotype, which revealed a partial deletion of the long arm of chromosome X - 46, X, del (X) (q 22.1), Turner syndrome was diagnosed. However, due to the presence of a Hurler-like facial phenotype, a genetic doctor suspected type I mucopolysaccharidosis (Hurler syndrome). The study of GAG urine by the method of one-dimensional electrophoresis revealed an increased renal excretion of heparan and dermatan sulfates, which is typical for mucopolysaccharidosis I, II and VII types.
When the girl was admitted to the clinic, her indicators of physical development were disharmonious: the body length (100 cm) corresponded to 3–10 percentile; body weight (17 kg) 90–97 percentile; the head circumference (54 cm) indicated macrocephaly and was above 97 percentile. Pronounced phenotypic features were noted (Fig. ): rough facial features, sunken nose, full lips, eye hypertelorism, macroglossia, short neck, low position of the auricles, stiffness of large and small joints, equino-varus deformity of the feet, kyphosis of thoracic spine. The hair was dark, eyes - brown, cornea is transparent without visual signs of turbidity. The child’s psychomotor development corresponded to her age: phrasal speech and adequate reaction to the environment. The muscle tone was moderately reduced. Active and passive movements were limited in large and small joints. Tendon reflexes from the hands and feet were alive, pathological reflexes were absent. She was able to walk independently. The examination of the heart revealed a sinus tachycardia with a heart rate of 133–143 per minute, normal position of the electrical axis of the heart, incomplete blockade of the right leg of the bundle, and a slight decrease in the repolarization processes in the myocardium in the form of the T wave flattening. The echocardiogram detected degenerative changes of the mitral and aortic valves with insignificant stenosis, the presence of diagonal trabeculae in the cavity of the left ventricle, and normal dimensions of the heart cavities.
The ultrasound scanning of the abdominal organs and kidneys revealed hepatic splenomegaly (6.5 and 3 cm, respectively) with diffuse changes in the liver parenchyma and a large number of enlarged lymph nodes in the gates of the liver and mesenteric lymph nodes. An increase in the gallbladder and thickening of its wall were also revealed. An increase in kidney volume and bilateral nephroptosis was diagnosed.
The ultrasound examination of the pelvic organs showed the location of the uterus in a typical place, its outline was even and drop-shaped, and the structure of the myometrium was homogeneous. At the site of the projection of the right ovary, the avascular structure was of somewhat reduced echogenicity, an oval shape, 1.0 × 0.5 cm in size with a clear and even contour of the homogeneous structure. The left ovary could not be clearly visualized.
The radiographic examination of the hands revealed coarsening and expansion of the phalanx, hypoplasia of the terminal phalanges, and a backlog of bone age for 1.5 years. Radiography of the shins and knee joints showed valgus deformation of the shins of the legs, flattening of the epiphyses, and osteoporosis.
Radiography of the hip joints, thoracic and lumbar spine noted asymmetry of the pelvic bones with a decrease in the head of the femur; flattening of the thoracic vertebrae and their cuboid shape in the lumbar region. All these x-ray changes, according to the conclusion of a radiologist, are characteristic of mucopolysaccharidosis, mostly of types II and I.
The examination of the oculist revealed a high degree of myopia with astigmatism of both eyes.
Clinical blood and urine tests revealed no pathology. Biochemical indicators, reflecting the state of the main types of metabolism, were normal.
The results of the study of the amino acid spectrum of blood serum and urine corresponded to physiological values. The level of thyroid hormone, thyroid stimulating hormone and somatomedin C in the blood serum was normal.
The study of lysosomal enzymes showed normal alpha-L-iduronidase activity and a sharp decrease in the activity of iduronate sulfatase in dry blood stains: 0.001 μM/l/h, at a rate of 2.5–50 μM/l/h. The result of molecular genetic analysis in exon 9 of the IDS gene revealed a new, non-registered (in the international database of HGMD professional) deletion in the hemizygous state. This deletion was not detected in the girl’s father, but was detected in the mother in a heterozygous state. |
pmc-6498627-1 | We present a 6 years old boy, presented soon after birth with erythematous eruption and hemorrhagic blisters (pernio), initially on the palms. Subsequently the rash spread over the entire body, accompanied with solitary subcutaneous nodules and violaceous periorbital swelling. His rash was worse during fever episodes. He was hospitalized multiple times at a tertiary pediatric unit with the clinical picture of severe inflammation. No immunisations were administered after the age of 3 months []. Three consecutive skin biopsies were performed from active efflorescences. They showed inflammation with the presence of lymphocytes, neutrophils, macrophages and mastocytes (CD117+). Some parts showed leukocytoclasis. Several autoimmune and autoinflammatory syndromes were considered in the differential diagnosis, including Sweet syndrome, Mevalonate kinase deficiency, CINCA/NOMID and leukocytoclastic vasculitis.
At the age of 1 year 5 months, he was started on methylprednisolone 1 mg/kg.d-1 with a reasonable effect on the rash and fevers. However, all attempts to taper the dose led to immediate relapse of the symptoms. Succesively, hydroxycloroquine and methotrexate were attempted as GC sparing agents, but they were soon withdrawn due to lack of any clinical effect.
The boy presented to us at the age of 2 years and 10 months. He was looking pretty unwell, with elevated daily temperatures reaching 39.9 °C, persistent skin eruption with nodules, livid and red papules and macules on the head, body, upper and lower extremities, palms and soles. Purple periorbital swelling was also present (Fig. ). Hypertrichosis was noted all over the body. Subcutaneous adipose tissue was significant for lipodystrophy. The arms, shoulders and face had well demarcated outline of the muscles, which gave the false impression of increased muscularity. The parents recalled episodes of joint pain and swelling of knees and fingers, but there was no objective evidence of contractures or joint space narrowing. The face was characteristic for atrophic facial musculature and absence of buccal fat pads, thus giving him an appearance of an old-man. He also had hypertelorism and epicanthus. Other symptoms were cough, tachydyspnea and hepatomegaly. The patient appeared very stunted for his age group. Age- and sex-specific growth evaluation showed significant short stature (− 4.1 SDS) and a decreased weight (− 2.3 SDS), . His bone age, according to Greulich and Pyle’s atlas, was 1 year 3 months (<− 2.0 SDS). Blood workup showed elevated CRP - 114.09 mg/L (0–5.0), neutrophilia, anemia with serum iron level < 2 mcmol/L (7.2–21.5). Thorough investigation showed no cardiac, pulmonary or neurologic involvment at the time.
CANDLE syndrome was suggested as the most probable diagnosis after discussion and evaluation of the patient’s medical history and current status. Blood samples from the child and both parents were sent to NIH for genetic testing. The patient was found to have compound heterozygous mutations in the PSMB8 gene (p.A92V/p.K105Q). Both parents are carriers of one mutation. |
pmc-6498662-1 | Our patient was a 56-year-old Caucasian married man with height 172 cm, weight 75 kg, and body mass index 25.4 kg/m2. He was admitted to our emergency department for severe dyspnea and desaturation.
The patient had a history of heavy smoking (30 pack-years) and no alcohol intake. In the last year, he had had two hospitalizations for acute exacerbation of COPD and was classified as Global Initiative for Chronic Obstructive Lung Disease class C. He was admitted to the ICU and eventually was tracheostomized. After his ICU stay, he was decannulated and actually showed a former closed tracheal stoma. Moreover, he had type 2 diabetes mellitus and hypertension, and he presented with a former closed tracheal stoma after his last ICU admission for COPD exacerbation. His medication history included ramipril, pantoprazole, and inhalation indacatarol/glycopyrronium.
At arrival, the patient showed hypercapnic respiratory acidosis (pH 7.24, partial pressure of oxygen 45 mmHg, PaCO2 70 mmHg, HCO3− 32 mEq/L). Standard medical therapy and noninvasive ventilation (NIV) were immediately started. The result of his neurological examination was normal with a Glasgow Coma Scale score of 15. His heart rate was 106 beats/min, peripheral oxygen saturation was 86%, noninvasive blood pressure was 135/85 mmHg, and body temperature was 37.8 °C. A chest computed tomographic scan showed a centrilobular emphysema and a bilateral fibrothorax (Fig. ).
A few hours after admission, the patient was intubated for worsening mental status and worsening respiratory acidosis (pH 7.18, PaCO2 85 mmHg). Mechanical ventilation in pressure support mode was started in the ICU associated with salmeterol and fluticasone 50 μg/100 μg inhalational therapy every 8 h. Sedation was obtained by titrating propofol infusion to obtain a Richmond Agitation-Sedation Scale score of − 1. On the basis of white blood cell count of 22 × 109/L, high procalcitonin serum level 12 ng/ml, and strong suspicion of a pulmonary infection, bronchoalveolar lavage was collected, and intravenous broad-spectrum empiric antibiotic therapy with piperacillin-tazobactam 4.5 g every 8 h and vancomycin 500 mg every 6 h was started. After 72 h, qualitative bronchial cultures showed a negative Gram stain and heavy growth of Pseudomonas aeruginosa. At this point, intravenous cefepime 2 g every 8 h was started.
On day 4 after admission, owing to the severity of lung infection, hypercapnic respiratory acidosis worsened to pH 6.98 and PaCO2 157 mmHg despite profound sedation and the maximization of minute alveolar ventilation. A low platelet count of 50,000 cells/μl was recorded. ECCO2r was started through a 16-French dialysis bilumen catheter inserted into the right femoral vein using continuous renal replacement therapy (CRRT) (Diapact® system; B. Braun Medical, Milan, Italy) with a Diacap Acute® filter (B. Braun Medical). The extracorporeal circuit was regionally anticoagulated with heparin administered prefilter and protamine sulfate administered postfilter (Fig. ).
Table shows blood gas analyses before, during, and after ECCO2r treatment. The patient’s PaCO2 dropped to 54 mmHg and pH increased to 7.21 after 6 h of treatment. The Diacap Acute® filter was replaced every 24 h during ECCO2r. On day 6 after admission, because PaCO2 consistently less than 60 mmHg, ECCO2r weaning was attempted, and the patient was switched again into pressure support mode. ECCO2r was started again 2 h later because of a rise in PaCO2. On day 7 after admission, the patient was successfully weaned from ECCO2r. Under pressure support ventilation, he was able to maintain an acceptable PaCO2 level (59 mmHg). On day 9 after admission, the patient became febrile with associated hypotension and increased serum lactate level. Multiple organ failure developed during the following 48 h. On day 11 after admission, blood cultures evidenced multidrug-resistant P. aeruginosa.
The extracorporeal circuit was primed two times, first with 1 L of NaCl 0.9% + 10,000 IU of unfractionated heparin and then with 1 L of NaCl 0.9%. A 500-IU/ml heparin solution was prepared and infused prefilter at 0.15 IU/ml/h of blood flow (Fig. ). A protamine concentration of 5 mg/ml was infused to match the heparin infusion rate []. ECCO2r was started at a blood flow of 300 ml/min and increased slowly to 450 ml/min to maximize CO2 removal. |
pmc-6498684-1 | A 4-year-old Japanese girl had fever and swelling in the right leg, with marked elevation of C-reactive protein (CRP) levels. Based on computed tomography, echocardiography and skin biopsy, she had been diagnosed with Takayasu arteritis at the age of two years. Due to aggravated inflammation, blood flow decreased in her legs, and part of her right leg became necrotic. As she had been resistant to standard therapy with prednisolone or tocilizumab without monitoring plasma concentrations, we started to administer IFX (day 0). IFX was given at a dose of 5 mg/kg on days 0 and 10. Although the levels initially decreased from 8.7 (day 0) to 1.6 mg/dL (day 10), CRP contents elevated again on day 23 (9.0 mg/dL), and IFX was administered at 10 mg/kg on the same day. Body fluid leakage from the inflammation sites in her legs was observed. Because blood IgG levels were lower than standard value, immunoglobulin (2.5 g) has been administered on days 17, 31, 37, 45, 51, 59, 65, 72, 85 and thereafter once a week for at least a few months.
Plasma IFX concentrations were measured by LC-MS/MS with nano-surface and molecular-orientation limited (nSMOL, Shimadzu, Kyoto, Japan) proteolysis [, ]. Based on the clinical courses of blood CRP and IFX levels (Fig. ), trough IFX levels were decreased from 23.6 μg/mL (day 10) to 2.5 μg/mL (day 23). Dosages and intervals of IFX administrations were then adjusted according to the trough IFX levels. IFX was given biweekly at 8 mg/kg per administration. Plasma IFX levels gradually increased, and CRP levels decreased to around 2 mg/dL 40 days after IFX administration. Inflammation was suppressed, and the dosage of prednisolone could be gradually decreased. CRP levels transiently elevated to 5.8 and 7.0 mg/dL after infection on days 87 and 126, respectively. Blood culture results confirmed the presence of gram-positive cocci. ADA against IFX was not detected using the enzyme-linked immunosorbent assay kit (Somru BioScience, PEI, Canada). During the observation period, no renal failure was observed. It is noteworthy to mention that a similar pattern -initial decreases followed by increases- was observed in the clinical courses of IFX and IgG (Fig. ). |
pmc-6498687-1 | A 19-year-old HIV- negative female was found to have multiple lung nodules by the chest X-ray during the physical examination. She had no symptoms at all such as chest tightness, cough or low fever. Physical examination and routine laboratory data showed no other abnormalities. Tumor markers (CEA, AFP, CA19–9, CYFRA21-1, NSE and SCC) were all negative. Sputum was negative for acid-fast bacilli in three occasions.
The chest computer tomography (CT) revealed multiple round nodules in both lungs. Nodules have smooth borders and the density of the nodules is relative uniform. The largest one is located near the apex of the upper lobe of the left lung measuring 2.2 × 2.4 × 2.1 cm in size by CT (Fig. ). We initially believed that these lesions are either primary benign tumor such as leiomyomas or reactive processes like tuberculosis since clinical and radiographic findings did not suggest any malignancy. A diagnostic biopsy was performed in the left thoracic cavity through thoracoscopy. In the course of the procedure, many dark-red masses which had different size were identified in the left lung (Fig. ). A tumor with a size of about 2.0 × 3.0 cm was wedged.
Microscopically, the tumor was composed of thin-walled vessels lined by flattened endothelial cells. Stromal cells between vascular spaces were spindled or round, some of which are vacuolated. The nuclei ware medium-sized and mitotic figures were rare (Fig. ). Immunohistochemical stains for vascular markers CD31, CD34 and D2–40 were positive and SMA was also positive in this tumor. HHV-8 was negative (Fig. ). Morphological features were those of pulmonary spindle cell hemangioma. On follow-up, 15 months after surgery, the patient was asymptomatic, and did not show any signs of tumor growth through the chest CT in 15 Apr. 2019 (Fig. ). |
pmc-6498699-1 | A 49-year-old woman presented with 2 weeks of peripheral vision loss and intermittent, painless, ten-minute episodes of peripheral “prism-like” photopsias. Her vision loss progressed and became more persistent while intruding bitemporally towards central fixation. She denied other ocular or systemic symptoms. Her past medical history was notable for a 15-pack year smoking history. She had no personal or family history of ocular or autoimmune disease.
At her initial visit, her best-corrected visual acuity (BCVA) was 20/30 in the right eye (OD) and 20/25 in the left eye (OS) with intraocular pressures (IOP) of 11 and 12 mmHg, respectively. Anterior segment and fundus exam, as well as laboratory evaluation and neuroimaging, were unremarkable. Lumbar puncture demonstrated elevated protein with negative oligoclonal bands and normal IgG index. Her presentation was concerning for bilateral optic neuropathy, and she was treated with IV Methylprednisolone 1000 mg daily for 5 days. She noted that steroid treatment arrested progression of her visual symptoms.
At the one-month follow-up, she reported stability of her visual symptoms. BCVA was 20/30 in both eyes (OU) with IOP of 16 and 17 mmHg OD and OS, respectively. Exam was notable for trace vitreous cell OU, retinal venous sheathing and retinal whitening OU. Widefield Optos color fundus photos and autofluorescence (Fig. ), exhibited peripheral regions of RPE hyperautofluorescence, demonstrating areas of photoreceptor and RPE degeneration. Fluorescein angiography (FA) demonstrated areas of perivascular hyperfluorescence that increased in intensity with time, consistent with leakage and retinal periphlebitis. Indocyanine green angiography (ICG) demonstrated choroidal hypercyanescence and dilated choroidal vasculature OU (Fig. ). Humphrey visual fields (HVF) demonstrated a temporal field deficit OD and peripheral constriction with a central island remaining OS (Fig. ), which corresponds to the retinal changes observed by fundus autofluorescence.
She was admitted and treated with high dose IV methylprednisolone. Repeat MRI of the brain noted increased FLAIR signal, T2 enhancement and restricted diffusion of the left optic nerve, concerning for optic neuritis (Fig. ). CT of the chest revealed mediastinal and left hilar adenopathy. Fine needle aspirate (FNA) biopsy revealed a poorly differentiated neuroendocrine carcinoma.
She was diagnosed with limited stage SCLC, chorioretinitis and optic neuritis consistent with CAR. An autoantibody panel was positive for anti-recoverin and negative for other CAR-associated antibodies. Electroretinography (ERG) was scheduled but was not obtained due to progression of her malignancy and worsening clinical course. She underwent treatment with carboplatin, etoposide and radiotherapy, but she declined prophylactic brain radiotherapy. She was maintained on Prednisone 60 mg daily for 12 weeks before being tapered by 10 mg weekly to 10 mg daily.
At the six-month follow-up, her BCVA and HVF were stable (Figs. and ). Fundus exam demonstrated persistently attenuated vasculature, retinal whitening and development of choroidal and outer retinal scarring. She achieved and sustained remission until brain metastasis was detected 10 months after the initial onset of visual symptoms. |
pmc-6498767-1 | The patient is a 57-year-old woman previously diagnosed with Lyme disease based on
positive Lyme serological testing and systemic symptoms consistent with tickborne
disease. While on treatment for Lyme disease with oral clarithromycin and cefdinir,
she developed a painful erosive vulvovaginal ulceration consistent with conditions
such as LP or LS. The ulceration encompassed the right labium minus, the right
labium majus, the left labium minus, the vulvar vestibule, and the introitus (). The vulvar
architecture was altered with partial loss and adhesion of the right labium minus.
Routine culture for genital bacteria performed at a commercial laboratory was
negative, and the patient was seronegative for syphilis. Therefore, further
investigation to ascertain the cause of the condition was undertaken. The
differential diagnosis included various lichenoid disorders, sexually transmitted
infections, and hypersensitivities. After identification of B
burgdorferi by culture and by histological examination, alternative
antibiotic therapy was prescribed. The condition resolved after 5 months of
treatment with topical clindamycin and oral doxycycline (). |
pmc-6498768-1 | A 72-year-old male with new-onset heart failure and severe mitral regurgitation
underwent coronary angiography, which demonstrated a 60% proximal-left anterior
descending (LAD) stenosis, an 80% ostial-second diagonal (D2)-branch
stenosis, a 90% proximal-first obtuse marginal (OM1) stenosis, an 80%
mid-right coronary artery (RCA) stenosis, and a 95% distal-RCA stenosis; his left
ventricular ejection fraction was 35% with posterobasal akinesis seen on
ventriculography. A radionuclide uptake study showed viability of the inferolateral
wall and anteroapical septum; the base of the posterior wall was not viable. A
transesophageal echocardiogram confirmed severe eccentric mitral regurgitation. He
electively underwent 4-vessel coronary artery bypass grafting consisting of a left
internal mammary artery (LIMA) → LAD, saphenous vein graft (SVG) → D2,
SVG → OM1, and SVG → RCA; he also underwent a MVR with a #29 bovine
pericardial valve.
Postoperatively on the day of his surgery, he went into sustained VT, which on
cardioversion degenerated into ventricular fibrillation and required cardiopulmonary
resuscitation. He was ultimately successfully resuscitated, and was started on
intravenous amiodarone, lidocaine, and β-blockers; he also had an intra-aortic
balloon pump (IABP) inserted at the bedside. Over the next several days, he
continued having multiple episodes of sustained and hemodynamically unstable VT (up
to 5 per 24 hours) despite ongoing antiarrhythmic drug therapy (total amiodarone
dose: >12 g); he also had a flail chest from multiple rib and sternal fractures
sustained during his many episodes of cardiopulmonary resuscitation.
On the 12th postoperative day, a decision was made to proceed with a combined sternal
repair and open chest epicardial catheter ablation in order to stabilize the
patient’s condition. |
pmc-6498772-1 | A 62-year-old female with history of left renal calculus presented to the emergency
department with fatigue, syncope, 3 episodes of hematemesis, and 2 episodes of
melena over the past 24 hours. Physical examination revealed an afebrile healthy
female, without abdominal or flank tenderness. Her presenting hemoglobin (hgb) was
8.2 g/dL without leukocytosis. No urinalysis was obtained due to absence of any
urinary symptoms. At this point, she did not have any symptoms of pyelonephritis.
She was admitted to the intensive care unit, where her hematemesis continued. Repeat
hgb after 1 day dropped to 6.6 g/dL. No abdominal imaging was obtained. Bedside
esophagogastroduodenoscopy (EGD) revealed a large amount of clotted blood in the
stomach, unamenable to lavage (). Continued hematemesis prompted left gastric arterial
embolization; however, the patient continued to have hematemesis. Repeat EGD after 4
days revealed persistent fresh blood in the stomach despite lavage. The fundus and
body were empirically injected with epinephrine to achieve hemostasis. Her hgb
stabilized and she was discharged home after a few days.
During a follow-up clinic visit after 4 weeks, she was found to have a left flank
pain, fever, headache, and nausea. Patient’s hgb was 5 g/dL with positive fecal
blood test. In the interim, she had intermittent melanotic stool with no
hematemesis. She was readmitted to the hospital where an EGD showed a fistulous
tract draining pus into the gastric fundus. A colonoscopy revealed a fistulous tract
draining pus and blood into the descending colon. Epinephrine was injected and
hemostasis was achieved. Gastric biopsy showed mild chronic gastritis, reactive
epithelial changes, and negative for malignancy. A computed tomography (CT) scan of
the abdomen and pelvis with intravenous contrast showed a left renal staghorn
calculus, a peripancreatic and perirenal fluid collection suspicious for abscesses,
and possible presence of fistulous tracts connecting the perirenal fluid collection
to the gastric wall and the descending colon (). A barium enema demonstrated a
fistula at the level of splenic flexure with contrast extravasation into the left
upper quadrant of the abdomen (). Serum amylase, lipase, carcinoembryonic antigen, and
carbohydrate antigen 19-9 were normal. Urinalysis was suggestive for urinary tract
infection, and urine culture grew Enterococcus faecalis. The
patient was started on intravenous ceftriaxone and later switched to intravenous
gentamicin once the sensitivities came back.
The patient underwent exploratory laparotomy with complete left nephrectomy, complete
splenectomy, distal pancreatectomy, partial colectomy of the descending colon, and
repair of the reno-gastric fistula. The pathology report from the left kidney
confirmed granulomatous inflammation with the presence of multinucleated giant cells
consistent with the diagnosis of XGP. A follow-up CT scan of the abdomen and pelvis
after 2 weeks did not show recurrence of any abscess or fistulas. After successful
treatment, her hgb improved and she was discharged home with an uncomplicated
postoperative course. |
pmc-6498773-1 | An 85-year-old Caucasian male presented with 2 to 3 months of weight loss and
progressive fatigue. Past medical history was notable for hypertension,
hyperlipidemia, and chronic kidney disease (stage III with baseline Cr 1.6). Home
medications included amlodipine 10 mg daily and chlorthalidone 25 mg daily.
Vital signs were blood pressure 162/63 mm Hg, pulse rate 64 beats per minute,
respiratory rate 14 breaths per minute, and temperature 98°F. Physical examination
was remarkable for mucosal pallor.
Laboratory studies were notable for anemia with a hemoglobin of 6.6 mg/dL, acute
renal failure with a serum creatinine of 10.1 mg/dL, positive antinuclear antibody,
positive MPO, positive PR-3, and positive ribosomal antibodies. Serum ANCA was
negative. Urinalysis was notable for proteinuria (3+) with red blood cells. The
24-hour urine protein was 2416 mg. Kappa to lambda light chain ratio was elevated at
108.3. Serum protein electrophoresis was significant for an elevated monoclonal IgG
protein of 4676 mg/dL (reference range = 700-1600 mg/dL) with kappa light chains
(see ).
Given the acute renal failure with hematuria, proteinuria, and laboratories
suggestive of MM and AAV, a renal biopsy was warranted to confirm a diagnosis. The
biopsy assessed 23 glomeruli, none sclerotic. The biopsy was significant for mild
mesangial expansion, diffuse acute tubular injury, and atypical casts with a
granular to fractured appearance with a surrounding cellular reaction (). IF demonstrated no
glomerular or extraglomerular staining with IgG, IgA, IgM, C3, C1q, fibrin, or
lambda light chains. The intratubular atypical casts demonstrated strong monoclonal
staining with kappa light chains. On electron microscopy, the glomeruli were
unremarkable with intact foot processes on the basement membranes. No immune complex
dense depositions or fibrillar deposits were identified.
Given clinical concern for MM, a bone marrow biopsy was performed. It demonstrated
atypical plasmacytosis consistent with MM. Plasma cells represented 65% of the
marrow. The patient’s MM was treated with bortezomib and 5 sessions of 1.0 volume
plasma exchange with albumin. Hemodialysis was initiated for rapidly worsening renal
failure. Unfortunately, there was no significant renal recovery, and the patient
remained hemodialysis-dependent. |
pmc-6498821-1 | This patient, aged 13 months, underwent HSCT. He, at age 13 years, underwent carpal tunnel surgery, following pain and decreased hand function. NCS for CTS were inconclusive. Post-operatively, there was resolution of pain and increased hand function. Pyridoxine-responsive homocystinuria was diagnosed at age 15 and he began oral pyridoxine therapy with good response. At age 16, he developed painful feet, similar in character to his hand pain prior to carpal tunnel surgery. He was reluctant to wear shoes secondary to the pain, would only wear slippers and would often rub his feet and had increasing refusal to walk. NCS were inconclusive, with normal distal tibial motor responses and some large polyphasic units on EMG of AHB. The neurologist's opinion was that the symptoms were consistent with a nerve compression syndrome. Bilateral tarsal tunnel release was performed at age 17 years and 10 months.
The operative report described a medial incision. The posterior tibial nerve was identified posterior to the medial malleolus and then explored distally. Both medial and lateral plantar nerves were identified and released. Tenosynovitis was debrided. Standing transfers were permitted post-operatively. He underwent ophthalmological and dental examinations under the same general anaesthetic. He was discharged home the day following surgery and described complete resolution of symptoms at 6 week follow-up. |
pmc-6498823-1 | A 7-month-old male was referred to our hospital due to poor linear growth and excessive weight gain (Figure ). He was fed a combination of breast milk and formula and had begun to sleep through the night a few months before presentation. He was the product of a healthy, full-term pregnancy; newborn screening tests were normal. There was no prior history of hypoglycemia or symptoms suggestive of hypoglycemia, seizures or midline cranial defects. His neurodevelopment was appropriate for age. He had not received corticosteroids. His growth chart showed a marked decrease in length percentiles from 73rd to 5th between ages 4 and 7 months, with a length-for-age z-score of −1.66 SD at the time of our evaluation. On physical examination, he was obese and had plethoric moon facies (Figure ); abdominal examination was difficult and could not exclude organomegaly or an abdominal mass.
An evaluation for CS was performed (Table ). Initial laboratory studies included serum cortisol and plasma ACTH in the afternoon, which were 14.4 mcg/dL and 12 pg/mL, respectively. Thyroid function tests were normal and, although insulin-like growth factor 1 (IGF-1) was low, insulin-like growth factor binding protein-3 (IGFBP-3) was normal. Diurnal assessment of adrenal function revealed that midnight (2400 hours) serum cortisol concentration was high on two occasions (10.4 and 7 mcg/dL), and despite appropriately high serum dexamethasone, administration of low-dose dexamethasone did not suppress his morning serum cortisol (9.8 mcg/dL). Two twenty-four hour UFC measurements were not elevated, but these data were probably unreliable owing to observed leakage around the bladder catheter and low urine creatinine excretion, suggesting incomplete collection.
A pituitary magnetic resonance imaging (MRI) study was normal. Abdominal ultrasound did not show adrenal pathology, but incidentally revealed hepatomegaly. Further diagnostic evaluation showed markedly elevated transaminase levels (AST 2001, ALT 921 U/L) and hypertriglyceridemia (779 mg/dL) as well as recurrent fasting hypoglycemia with plasma glucose levels as low as 21 mg/dL. Molecular genetic testing identified a hemizygous, known pathogenic mutation in PHKA2 (c.3505C>T), confirming the diagnosis of hepatic phosphorylase kinase deficiency (Type IXa GSD). The patient's hypoglycemia resolved after the introduction of a regimen of frequent carbohydrate- and protein-enriched feedings. Once a period of stable euglycemia (blood glucose levels ≥70 mg/dL) had been achieved, an overnight low-dose dexamethasone suppression test was repeated, which showed normal suppression of the morning serum cortisol to 1.8 mcg/dL (Table ). This suggested resolution of a hypercortisolemic state that was secondary to unrecognized recurrent hypoglycemia. Following the initiation of dietary therapy, the patient's statural growth improved, and his weight fell from the 76th to the 50th percentile (Figure ), and his cushingoid appearance improved (Figure ). |
pmc-6498832-1 | A 3-month-old girl came to medical attention because of apparent pain, irritability, and difficulty with mobilization. Swelling and erythema over her interphalangeal joints were noted and the patient was referred to a rheumatologist who confirmed polyarthritis affecting her hands and wrists. The patient was also found to have a hoarse voice. Further investigations revealed signs of right vocal cord paresis and gastroesophageal reflux. She was the second child to a nonconsanguineous healthy caucasian couple, born at term with normal birthweight and height.
At the age of 4 months, erythematous nodules progressed over multiple areas of her body. The diagnosis of FD was suspected and she was found to carry a homozygous mutation (c.458A > G [p.Tyr153Cys]) in the ASAH1 gene.
Initial neurological assessment revealed signs of mild delay in her gross and fine motor skills presumed to be secondary to arthritis. To further assess her neurological status, she underwent electroencephalography, which was unremarkable, and electromyography (EMG), which showed no evidence of peripheral neuropathy or myopathy. A decision was made for the child to undergo HSCT at the age of 8 months. Magnetic resonance imaging (MRI) done prior to transplant was unremarkable. Her initial ophthalmologic examination 4 months prior to transplant was normal. One cherry-red spot was identified on reassessment a few days prior to transplant.
She received a myeloablative conditioning regimen with targeted IV busulfan, fludarabine, and alemtuzumab, followed by a matched (6/6) unrelated cord blood transplant at the age of 9 months. Cyclosporin and mycophenolate mofetil (MMF) were used as graft vs host disease (GvHD) prophylaxis. The patient had no significant transplant-related complications and had full recovery of all three cell lines. No signs of acute or chronic GvHD were reported. Chimerism at day +475 was 100% donor cells.
Of note, her alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were elevated preceding the transplant (Figure ). On day +7, ALT and AST started to decrease toward normal levels, with the exception of an unexplained spike on day +25. Subsequent values remained within normal limits (Figure ).
In the first 12 months following HSCT, resolution of the skin nodules and significant improvement of her joint mobility were observed. Her arthralgia and arthritis resolved and pain and antiinflammatory medications were discontinued. Her gross and fine motor skills improved rapidly although she remained developmentally delayed for her age. Ophthalmological evaluation 6 months post-HSCT identified the same cherry-red spot with no change compared with previous examination.
At the age of 1-year-old (3 months post-HSCT), a computed tomography scan demonstrated corticosubcortical bilateral frontotemporal volume loss, hypodensity of the brain parenchyma, and mild ventriculomegaly. She began to show signs of hypertonicity and irritability 12 months after HSCT with progressive loss of certain previously acquired skills. The following months were highlighted by the deterioration of her neurological status, increased autonomic dysfunction with severe constipation, and swallowing and feeding difficulties. The patient had multiple respiratory infections for which she required hospitalizations and admissions to the intensive care unit. She died of respiratory failure at the age of 37 months, 28 months after transplant.
A term male infant of nonconsanguineous healthy Caucasian parents was noted to have a hoarse voice since birth and painful occipital nodules appearing at 10 days of age. By 4 months of age, he developed multiple progressive painful nodules over his fingers, wrists, ankles, sternum, and back and lumbar areas. The clinical diagnosis of FD was made based on the classical clinical manifestations. Genetic workup identified a homozygous genotype for the same mutation in ASAH1 (c.458A > G [p.Tyr153Cys]).
Initial neurological assessment at the age of 5 months identified motor developmental delay with axial hypotonia. MRI showed a prominent ventricular system, bilateral prominent arachnoid sulci, and normal parenchyma at this age. Demyelinating-type conduction abnormalities involving motor and sensory nerves were noted on EMG at the age of 7 months. Reassessment of his neurological status at the age of 6 months revealed signs of upper motor neuron dysfunction including brisk tendon reflexes, clonus, and spasticity. Retinal cherry-red spots were reported on ophthalmological assessment.
At 7 months of age, thickened vocal cords, edema, and severe erythema of the arytenoids were reported on laryngoscopy. He had poor weight gain and microcytic anemia. The patient had normal kidneys and no hepatosplenomegaly.
The child underwent a matched (6/6) unrelated cord blood transplant at the age of 9 months following myeloablative conditioning with targeted IV busulfan, cyclophosphamide, and antilymphocyte globulin. A rapid resolution of the painful nodules was observed following the initiation of the conditioning chemotherapy. The patient experienced major improvements of joint stiffness and better mobility. The child did not develop any significant transplant-related complications and had full recovery of all three cell lines. Cyclosporin and MMF were used as GvHD prophylaxis. No signs of acute GvHD were reported. Chimerism studies showed 100% donor cells at 4 years posttransplant.
At 9 months posttransplant, a brain MRI showed stable findings compared with the pretransplant study. At 15 months posttransplant, signs of neurological deterioration became visible with loss of previously acquired motor milestones. A repeat MRI revealed progression in the dilatation of the ventricular system with cerebral parenchymal atrophy. The spine MRI was unremarkable. A video fluoroscopy swallowing study confirmed aspiration with an absent cough reflex. His overall clinical status continued to deteriorate with frequent hospitalizations for respiratory complications. The child died at 8 years old of respiratory insufficiency secondary to aspiration pneumonia. |
pmc-6498837-1 | A 25-year-old female Irish patient presented with recurrent episodes of rhabdomyolysis since childhood. The first episode occurred at the age of 22 months following a respiratory tract infection. At that time, her creatine kinase (CK) serum concentration was noted to be 250 000 U/L.
The family history indicated that both parents were well. However, two siblings (brother and sister) had sudden death at the age of 2 and 4 years more than 20 years ago following a short infectious illness with sudden deterioration over a period of hours. In both cases, the children became progressively weak with severe muscle pain and had evidence of rhabdomyolysis and myoglobinuria of uncertain etiology. Skeletal muscle histology and electron microscopy studies at postmortem evaluation were normal in both children, cardiac evaluation demonstrated dilated cardiomyopathy. Notes pertaining to their clinical episodes were not available. On first presentation, our patient had no hypoglycemia and no ketosis during the acute illness, but was initially treated as a possible long chain fatty acid oxidation defect due to the family history.
The patient had numerous subsequent admissions with similar presentations of extremely elevated CK concentration (1 000 000 U/L at the age of 9) associated with muscle pain. This was despite aggressive carbohydrate supplementation including nocturnal cornstarch. Her fat intake from food was continually restricted to approximately 40 g/d. Her total fat intake was supplemented with the use of MCT Oil (medium chain triglycerides supplement) and essential fatty acids in the form of walnut oil. Coenzyme Q10 at a dose of 100-200 mg daily was provided on an ongoing basis. The CK concentration was also raised between the episodes (500-2000 U/L). She was advised to limit her exercise to 20 minutes per day and have high-calorie drink prior to any physical activity.
Extensive investigations were performed over the presenting years with the lack of a definite etiology. Serial urine organic acid profile and the acylcarnitine profiles were normal. A fibroblast fatty acid oxidation study showed normal myristate and palmitate oxidation studies in fibroblasts. Genetic analysis for fatty acid oxidation defect (LCHAD, MCAD, CPT I, and CPT II) and McArdle disease was uninformative.
At the age of 16 years, mitochondrial respiratory chain activity measured in a muscle biopsy was normal, however morphological findings, such as intramyocellular lipid, were compatible with lipin-1 deficiency (Figure ). Her echocardiogram and electrocardiogram did not show any abnormal findings.
At the age of 19 years, DNA sequence analysis of the LPIN1 gene (all coding exons and flanking intron boundaries corresponding to the canonical transcript variant NM_145693.3) revealed the presence of a common pathogenic intragenic deletion within the LPIN1 gene (c.2295-866_2410-30del1763) encompassing exon 18 (HGMD accession: CG085181). However, a second mutation could not be identified.
Subsequently, the LPIN1 coding region was analyzed by reverse-transcriptase PCR (RT-PCR) from total RNA isolated from muscle tissue and conventional DNA sequencing (Figure A,B). In addition to transcripts lacking exon 18 or exons 18-19 (corresponding to the allele harboring the genomic exon 18 deletion), an alternative exon spliced in between exon 5 and exon 6 was detected in a significant proportion of transcripts (Figure C,D). Because this alternative exon, named exon 5a, corresponded to an alternatively spliced in-frame exon annotated only in an N-terminal LPIN1 transcript variant (NM_001261428.2), further targeted DNA-based sequencing was performed. Indeed, this identified a second heterozygous variant (NC_000002.11:g.11916284C>A), which was formally regarded a nonsense mutation introducing a premature stop-codon within exon 5a (which would correspond to NM_001261428.2:c.942C>A, NP_001248357.1:p.[Cys314*]; Figure ). RT-PCR of total RNA isolated from healthy skeletal muscle detected exon 5a also in transcripts containing the first (noncoding) exon of the canonical isoform (data not shown). However, because exon 5a is currently not annotated to be contained in this main reference transcript (NM_145693.3), further studies will be needed to clearly establish pathogenicity of the novel variant.
Segregation analysis in the patient's family revealed that her father and younger sister are heterozygous for the common pathogenic intragenic deletion (NM_145693.3:c.2295-866_2410-30del1763), while her mother was a heterozygous carrier of the variant within the alternative exon. Thus, the results of these molecular genetic analyses were formally consistent with the clinical diagnosis of LPIN1-associated rhabdomyolysis, due to compound heterozygosity for a known pathogenic deletion and potentially pathogenic novel mutation.
At the age of 25 years, the patient presented with acute muscle pain and weakness following prolonged fasting and strenuous exercise. A rhabdomyolysis crisis was confirmed with a CK of 500 000 U/L. She was admitted to intensive care unit (ICU) for a 2 week period over which period she lost a significant amount of weight. During her critical illness, she received an intravenous infusion of 10% dextrose at 1.5 times maintenance with added electrolytes, sodium bicarbonate, morphine, and dexamethasone. Intravenous carnitine was also provided as the patient had previously observed this to be clinically beneficial. She was treated symptomatically, with shortened fasting periods, corn-starch at night and an “unwell dietary regimes” with a mild restriction of fat (40 g per day) and supplementation with MCT oil and walnut oil for essential fatty acids and Liquigen 5 g daily. On day 11, her CK was monitored 4 hourly and was 1248 U/L. On discharge from ICU, this patient had generalized muscle weakness, stiff lower limb muscles (gastrocnemius), and bilateral drop foot requiring orthotic splints. Muscle weakness gradually improved after months of rehabilitative physiotherapy. Her drop foot has improved somewhat (power from 0/5 to 3/5 for dorsiflexion and extensor hallicis longus over 1 year) with areas of altered sensation anterolaterally below the knees consistent with bilateral residual common peroneal neuropathies (CPN). Serial nerve conduction/electromyography studies demonstrated bilateral CPN palsies and a background generalized myopathy. The most likely cause of this patient's weakness was a critical care neuromyopathy, which has improved with time, in addition to CPN palsies related to significant weight loss while critically ill. However, we cannot exclude the possibility that both defects were related to her lipin-1 deficiency. While myopathy has been reported in a few cases, CPN damage is not a known association of this rare metabolic disorder. |
pmc-6498866-1 | Patient 1 was a 22-year-old woman. The patient demonstrated severe feeding problems during infancy and was hospitalized three times for feeding issues. The patient had no history of developmental disability or seizures. The child of the patient was born at 35 weeks’ gestation. Delivery method was unreported. During labor, a protein intake of 1.0 g/kg/h was maintained. The infant's birth weight was 2150 g (10th-50th centile), with normal length and head circumference. The infant was prescribed a diet consisting of milk formula with 3.0 g of protein/kg/24 h, and demonstrated normal blood ornithine levels at 2 weeks of age, and normal development at 6 months of age upon follow-up. |
pmc-6498866-2 | Patient 2 was a 31-year-old woman of Salvadoran descent, who delivered three children. At 4 years of age, the patient first presented episodes of seizures and abnormal neurological findings and was diagnosed with HHH syndrome. The patient had developmental disability, manifested by expressive language and attention problems determined upon neuropsychiatric evaluation, and significant myopia. The patient was prescribed a diet consisting of protein restriction to 1.5 g/kg/d during childhood. The patient's weight was at the 25th percentile with height less than the 3rd percentile.
The patient's first pregnancy occurred at 18 years old. She had episodes of nausea and dizziness. She was maintained on a low-protein diet in the first trimester, but mild hyperammonemia was detected during the 11th and 12th week of pregnancy; as a result, protein intake was further restricted to 40 g/d. It was unclear if the patient was compliant or not. At 22 weeks gestation, the patient developed seizures, and was initiated with carbamazapine. Brain imaging showed multiple small calcifications of unreported cause, with normal cerebral angiography. The child was born at full term, via Cesarean-section. The baby girl had intrauterine growth restriction (weight <3rd percentile). Although the baby girl remained small, follow-up recorded a normal development at her 2 years of age.
Very little is described for the course of her second and third pregnancy. The second child was born via Caesarian section. A moderately elevated ornithine concentration (302 μM/L) was measured in the cord blood, but the levels decreased to normal in the newborn's blood 24 hours after birth. The patient's blood ammonia levels increased 24 hours postpartum and were given a treatment consisting of oral sodium benzoate and intravenous arginine. The patient responded well to the treatment. Follow-up showed normal growth and development for the child at 10 months of age.
The third child was born via repeat Cesarean section and had transient respiratory distress which required mechanical ventilation. No further information was given regarding the outcome of this child.
Upon follow-up, the patient was noted to have been prescribed more anticonvulsants, and had significant weight loss from 95 to 50 lb. The patient died suddenly at the age of 31 years and 9 months, with an autopsy revealing two firm nodules in the brain, one each in the left parietal and frontal lobes with no determined cause of death. |
pmc-6498866-3 | Patient 3 was a 24-year-old woman with HHH. Clinical picture included ataxia, tremor, seizure, developmental delay (IQ of 65), and abnormal electroencephalogram. The report notes at diagnosis that the patient's blood ammonia level was >300 μg/dL (N < 80), ornithine levels were 71-86 μM/dL (N < 15), and homocitrulline levels were 510-643 μM/24 h. The patient was prescribed a diet consisting of lactulose, arginine, and protein restriction, which resulted in a reduction on blood ammonia levels to 110-140 μg/dL and clinical improvement.
The patient was found to be pregnant at 8 weeks’ gestation, with blood ammonia levels of 120 μg/dL and ornithine levels of 75.6 μM/dL. The dietary protein intake was increased to 1.2-1.3 g/kg/d. A healthy male infant was delivered at 39 weeks’ gestation. The mode of delivery was not disclosed. During the delivery, maternal ammonia levels varied from 74 to 215 μg/dL. Upon follow-up at 16 months of age, the child's Bayley Scales showed normal development, and at age 5, the child had an IQ of 130. |
pmc-6498991-1 | The participant was a 21-years-old male patient with MELAS characterized by cytochrome c oxidase dysfunction. At the time of study, the participant suffered of severe mobility impairment (wheelchair limited), loss of hearing, partial blindness and dysphagia. Muscle weakness and asthenia were coupled with an exacerbated fatigue. From a cardiovascular point of view the heart function was reduced leading to the necessity to implant a DDDR pacemaker. The participant’s clinical characteristics were determined by qualified medical members of the research team (). Before testing, the participant abstained from physical rehabilitation for 48 h, caffeine for 12 h, and food for 3 h, and was not taking any drugs known to impact the response to the assessment procedures. This study was carried out in accordance with the recommendations of the Declaration of Helsinki. The protocol was approved by the Department of Neuroscience Biomedicine and Movement Science (Prot 227). Caregiver of the case gave written informed consent for the case participation in the study and publication of this case report. In order to better categorize the singular data of the participants with MELAS, a group of eight healthy age- sex-matched subjects served as control group (CTRL). All CTRL subjects gave written informed consent. CTRL subjects were healthy recreationally active men, demographic characteristics are reported in .
The participants visited the laboratory on three occasions separated by 24 h. The first visit comprised body composition testing (DXA), and the clinical assessments. At the second visit, the participants completed a familiarization with the interpolated twitch and in vivo mitochondrial respiration capacity protocols. At the third visit, the participants completed an in vivo mitochondrial respiration capacity protocol utilizing a Near-infrared spectroscopy device (NIRS) on the right plantar-flexor muscles. After 60 min of recovery, maximal voluntary torque (MVC), electrically evoked resting twitch (EET) and maximal voluntary activation (VMA) of the right leg extensors (LE) muscles were determiner with the interpolated twitch technique. Only for the participant with MELAS these evaluations were repeated after 12 weeks of RT.
From a clinical point of view, the participant with MELAS showed dysphagia to solids (he had a modified diet and assumed food integrators). He presented with easy fatigability and decreased muscle mass. No limitation of (main joints) range of motion was found at the upper and lower limbs. Muscle tone was not affected in a relevant way but needed some assistance to change posture (from supine to sitting posture as well as from sitting to standing posture).
The cognitive assessment battery utilized in this study was very limited due to the severe hearing loss, vision acuity deficits and hemianopia, in addition to the easy fatigue and eyelid ptosis. The evaluation was focused on the main cognitive deficits reported in the literature in the MELAS. The patient was perfectly oriented in the space-time parameters, but with important deficits of sustained and selective attention, with an easy distractibility. The participant demonstrated deficits in short-term and long-term verbal memory. The evaluation of executive functions estimated with Frontal Assessment Battery and Clock Drawing Test () revealed a lack of planning ability, verbal ideation and inhibitory control. Tests’ scoring are reported in .
Body composition (body fat and lean mass) was assessed by means of Dual energy X-ray absorptiometry using a total body scanner (QDR Explorer W, Hologic, MA, United States; fan-bean technology, software for Windows XP version 12.6.1) according to the manufacturer’s procedures. The scanner was calibrated daily against the standard supplied by the manufacturer to avoid possible baseline drift. Whole body scanning time was about 7 min. Data were analyzed using standard body region markers: upper and lower extremities, head, and trunk (pelvic triangle plus chest or abdomen). Additionally, the DXA scans were examined using non-standard body region markers to define thigh segments. The thigh region was delineated by an upper border formed by an oblique line passing through the femoral neck to the horizontal line passing through the knee (). All scanning and analyses were performed by the same operator to ensure consistency. In our lab the precision error (percent coefficient of variation with repositioning) of whole-body DXA measurements is 2.3, 0.5, and 2.8% for fat mass, lean mass and percent fat mass, respectively.
The assessment of in vivo mitochondrial respiration capacity was performed via a non-invasive approach of the muscle oxygen consumption (mVO2) as previously described by , ), . NIRS data were obtained using a device (OxiplexTS, ISS, Champaign, IL, United States), equipped with a standard acquisition probe (emitter detector distances of 2.0, 2.5, 3.0, and 3.5 cm). The values of oxygenated hemoglobin () and deoxygenated hemoglobin [HHb] were recorded at 4 Hz and expressed in micromoles using the Beer Lambert Law and multi-distance frequency resolved spectroscopy.
The NIRS probe was positioned longitudinally on the belly of the right plantar flexor muscles. The probe was secured with double-sided adhesive tape and a Velcro strap around the calf. After 30 min of warm-up period, the NIRS device was calibrated using a phantom with known optical properties A blood pressure cuff was placed proximal to the NIRS probe around the popliteal area. The blood pressure cuff was controlled with a rapid-inflation system (Hokanson E20, D.E. Hokanson) set to a pressure of >250 mmHg and powered with an air compressor.
The NIRS experimental protocol consisted of two measurements of resting mVO2 after the inflation of the blood pressure cuff for 30 s. mVO2 was calculated as the rate of change of the HHb signal during the arterial occlusion via linear regression. Following the resting measurements, participants performed a 30 s dynamic contractions of the plantar flexors muscle to increase mVO2. Upon relaxation, the recovery kinetics of mVO2 were measured using a series of transient arterial occlusions with the following timing: 5 s on/5 s off for occlusions 1–5, 7 s on/7 s off for occlusions 6–10, and 10 s on/10 s off for occlusions 11–20. Post-exercise mVO2 was calculated for each occlusion using a linear regression. The mVO2 recovery kinetics were determined by fitting the time-dependent changes during the recovery period to a mono-exponential curve described by the following equation:
where Yend is the level of variable measured at end-of-exercise and Yres refers to the amplitude of the response, TD represent the time delay (TD), and τ reflects the time constant of the recovery, a relative measure of muscle oxidative capacity (). Model variables were determined with an iterative process by minimizing the sum of squared residuals (RSS) between the fitted function and the observed values. Goodness of fit was assessed by visual inspection of the residual plot and the frequency plot distribution of the residuals, Chi square values, and the coefficient of determination (r2), which was calculated as follows:
with SSreg, the sum of squares of the residuals from the fit and SStot, and the sum of squares of the residuals from the mean.
Maximal voluntary and electrically evoked muscle contractions of the LE muscles were measured utilizing a custom-made setup (). Subjects were seated in an upright position with back support. The hip and the knee were flexed at 90°, and the right ankle were attached, via a strap and rigid steel bar, to a force transducer (DBBSE-100 kg, A2829. Applied Measurements Limited, Aldermaston Berkshire, United Kingdom). The output from the force transducer was amplified (INT2-L, London Electronics Limited, Sandy Bedfordshire, United Kingdom), and recorded at a sampling rate of 5 KHz with a PowerLab-16/35 data acquisition system (ADInstruments, Bella Vista, NSW, Australia).
In the participant with MELAS the determination of muscle cross sectional area via magnetic resonance imaging was not possible due to the implanted pacemaker. Therefore, LE voluntary muscle normalized force was calculated by dividing torque of the LE isometric maximal voluntary contraction (MVC), by the lean muscle mass of the corresponding muscles (nMVC) from DXA. Similarly, EET normalized force was calculated by dividing torque of the LE electrically evoked EET, by the lean muscle mass of the corresponding muscle (nEET).
M-waves were recorded during femoral nerve stimulation in the vastus lateralis muscle (detailed in next section). Pairs of full-surface solid adhesive hydrogel electrodes (H59P, Tyco Healthcare Group, Mansfield, MA, United States) were positioned lengthwise over the muscle belly, with an inter-electrode distance (center-to-center) of 20 mm. The ground electrodes were fixed over the ipsilateral patella. Light skin abrasion followed by skin cleansing kept electrical impedance below 10 kΩ. EMG signals were amplified with a pass-band of 10 Hz–1 kHz and digitized online at a sampling frequency of 5 kHz.
Each test procedure began with the determination of the maximal M-wave and EET responses in the resting LE muscle. Briefly, current intensity was progressively increased from 0 mA to the value beyond which there was no further increase in M-wave amplitude. The stimulus utilized for the study was set at the 125% of the intensity required to produce a maximal M-wave response. Electrical stimuli were delivered using circular (diameter 5.0 cm) self-adhesive electrodes (Dermatrode, American Imex, Irvine, CA, United States) positioned in the femoral triangle, 3–5 cm below the inguinal ligament, and the anode placed over the iliac crest. The EET were evoked in the passive muscle using electrical stimulation consisting of single square-wave pulses of 0.1-ms duration, delivered by a Digitimer DS7h constant-current stimulator (Digitimer Ltd., Welwyn Garden City, United Kingdom). The EET was measured 5 s after a 5 s MVC of the LE and this procedure was repeated six times. Consequently, EET was assessed in the potentiated state. The interval between the MVCs was 30 s. Peak torque, was assessed for each EET (). Voluntary activation of the LE muscles during the MVCs was assessed using a superimposed twitch technique (). Briefly, the force produced during a single twitch superimposed on the MVC was compared with the force produced by the electrically evoked EET produced, at rest, 5 s after the MVC.
Resistant training included 60 min three times a week of high-intensity strength training for an overall exercise duration of 12 weeks. Sessions started with 10 min of warm up which included active joint mobilization of lower and upper limbs. Then, the participant performed 3 sets of 10 reps of strength exercises at 85% of 1 repetition maximum (1RM). 1RM was determined by means of Brzycki method. Briefly, the participant executed progressive series of the isotonic exercise until the offered resistance was impossible to be sustained for 5/6 repetitions. The number of repetitions, and the relative workload, were used in the Brzycki equation. 1RM was adjusted every 2 weeks and the corresponded training load was increased. RT ended with stretching exercises for all the muscle involved in the training. All training sessions were supervised by a skilled kinesiologist.
Control group data and muscle function values measured in the participant with MELAS during six repetitions of isometric LE are presented as mean ± standard deviation. Due to the descriptive nature of this single case study any specific analysis was applied to the collected data. |
pmc-6499163-1 | The proband is a 24-year-old female and the only daughter born to unrelated and clinically unremarkable Chinese parents. There were no abnormal antenatal or postnatal issues of note, and her growth was normal. Her grades in school were below average, and her sports performance was ordinary. She obtained a junior college degree and was unmarried. She had previously been in good health, and the first concerns were raised when the patient was 18 years old. She developed paroxysmal unconsciousness and twitches affecting all four limbs after a cold, which subsided after about half a minute, with four similar attacks altogether. The brain magnetic resonance imaging (MRI) showed an abnormal signal in the T1/T2-weighted images of the bilateral putamen (), and the magnetic resonance angiography was normal. She received 0.25 g of levetiracetam daily for a year, and seizures did not recur.
Six months ago, she developed paroxysmal shaking in her left limb and a prickling-like pain in her left forearm, which subsided after 5–10 s, with a frequency of more than ten times per day. The above seizure could be followed by a generalized tonic clonic seizure (GTCS). She received adequate doses of levetiracetam and lamotrigine, but there were still more than ten attacks per day. Twenty days ago, she experienced twitches in her face and tongue, with a frequency too high to be calculated. The frequency of attacks on the left side and right side is approximately 5 to 1. Initially, the twitches subsided within 5 s, but gradually extended to approximately 60 s each time. Four days ago, she had continual GTCSs and was diagnosed as status epilepticus (SE) in our hospital. She was given midazolam intravenously and levetiracetam, clonazepam and phenobarbital. Two days ago, she had not developed GTCS again, but still had frequent twitches in her face. In our epilepsy department, we adjusted the medication to 1.0 g of levetiracetam every 12 h, 2 mg of clonazepam every 12 h and 100 mg of phenobarbital daily. No twitches had reappeared as of 8 days later.
On admission, physical examination showed the patient was in a state of somnolence, and she could basically cooperate with the inspection. She exhibited dysarthria and left central facial and tongue paralysis. There was mild weakness and hypotonia in all four limbs. The tendon reflex was decreased bilaterally. Furthermore, the muscles of her four limbs exhibited mild atrophy, with the left side more obvious.
A brain MRI showed hyper signals in the T2-weighted images of the symmetrical putamen, bilateral frontal and parietal cortices (). Twenty-four days after treatment, the cortical lesions had obviously improved (). Routine examinations of blood and cerebrospinal fluid (CSF) analysis were normal. The onconeural antibodies including anti-Hu, Yo, Ri, CV2/CRMP5, Amphiphysin, Ma2/Ta, recoverin, SOX1, titin, zic4, GAD65, and Tr (DNER), and the neuronal surface antibodies including anti-NMDA-R, CASPR2, AMPA1-R, AMPA2-R, LGI1, and GABAB-R in the serum and CSF were negative. Blood and urine metabolic screening were normal. There was one significant admission laboratory result: the blood lactate level was 4.5 mmol/L. The video electroencephalogram (EEG) showed there were significant diffuse slow waves in the right frontal lobe and temporal lobe, a small number of sharp waves in the right occipital and posterior temporal regions, and occasional sharp waves in the right temporal region during the interictal phase. During the ictal phase, we found the EEG rhythmic changes first appeared in the right frontal and anterior temporal regions, accompanying complex partial seizures. The brainstem auditory evoked potential, visual evoked potential, electromyography, and nerve conduction velocity were normal.
The Montreal Cognitive Assessment score was 25 on a scale ranging from 0 to 30. A biceps brachii muscle biopsy showed no ragged-red fibers (RRF). Under electron microscopy, there were damaged fibers in the striated muscle tissues and disorder arranged muscle nodes with increased glycogen and mitochondrial electron density.
Taking advantage of the PCR-Sanger sequencing technology in analyzing the mitochondrial genome, the patient was identified as having the m.10191T>T/C mutation in her blood and hair specimen; her aunt only had the m.10191T>C mutation in her hair specimen; however, her parents had no detectable mutation ().
The proband's aunt is 46 years old, with normal stature, hearing, and vision. She developed paroxysmal GTCSs at the age of 42. Her brain MRI showed multifocal lesions of the cortices at that time. She received carbamazepine 100 mg bid and gradually developed dysarthria. Three years later, she manifested twitches of the right side, followed by GTCS that occurred 4 times per day. Furthermore, she exhibited confused consciousness accompanied by occasional right extremity weakness. The brain MRI showed larger lesions than those that were present 3 years before, MR spectroscopy showed decreased N-acetylaspartate and a significant bimodal lactate peak (). Physical examination showed weakness of her right upper extremity (III/V). She was diagnosed with MELAS and given carbamazepine, levetiracetam and coenzyme Q10, as well as multivitamins. At present, she lives independently. The proband's aunt's son died of respiratory failure at the age of 8, but the details were not clear. The family tree is shown in .
All subjects gave written informed consents and written consent to permit publication of clinical details. The study was approved by the Medical Ethics Committee of Beijing Tiantan Hospital, Capital Medical University and was carried out in accordance with the Declaration of Helsinki. |
pmc-6499182-1 | In the studied family, a 43-year-old gravida at 11 weeks of gestation (the proband, II-4), her mother (I-2) and sibling (II-1) were presented with abnormal fusions of joints (). The clinical features of hands and feet are listed and provided in . In the initial observation on the fingers of the proband (II-4), it was noticed that both thumbs were normal (); however, finger 2–5 lacked creases on flexor and extensor surfaces of the interphalangeal joints (), and was not able to flex (). Further examination on elbow joints demonstrated that she had normal abilities to move them and was able to touch her shoulder with hands (). On checking both feet of the proband (), we found abnormalities similar to the fingers: (i) both thumbs were normal; (ii) both toe 2–4 lacked creases on flexor and extensor surfaces of interphalangeal joints; and (iii) the symptomatic toes were not able to flex. Furthermore, a little short phalange of second toe was noticed in both feet (). Given that the proband was a gravida at 11 weeks of gestation, X-ray examinations that could enable uncovering of the status of the osseous fusion were not applied to her. Patient I-2 and II-1 had similar symptoms as the proband, therefore, detailed examinations including X-ray examinations were supposed to provide alternative evidences for the proband. Like proband, both patients I-2 and II-1 had normal elbows. For patient I-2, proximal interphalangeal joint osseous fusion of left finger 4–5 and right finger 4–5 were observed (), but tarsal-carpal coalition was not found. Foot radiographs revealed that patient I-2 had proximal interphalangeal joint osseous fusion of left toe 3–5 and right toe 2–4 (), and she had bilateral talonavicular coalition and talocalcaneal coalition of feet (). For patient II-1, both observation and radiographs showed proximal symphalangism of left fingers 3–5 and right fingers 4–5 (). Proximal symphalangism was evident in right toe 3–4, while distal interphalangeal joint osseous fusions were observed on left toe 2–5 (). Furthermore, fusion of multiple tarsal bones was found in patient II-1 (), that is, bilateral talonavicular coalition, bilateral talocalcaneal coalition, coalition of the cuboid bone and the third cuneiform bone on left side as well as coalition of the third cuneiform bone and the third metatarsal bone on the left side. Pure-tone audiometry (125 Hz–8 kHz) showed normal hearing thresholds in all the members.
WES was performed on the proband and total of 136,155 variants, including 122,267 single nucleotide variants, 13,882 indels (deletions and insertions, <50 bp) and 6 copy number variations were identified by WES, followed by annotation, filtration and prioritization steps to obtain the variants causing symptoms in the studied family (). The results indicate that NOG is the most likely candidate gene. Pathogenicity analysis was performed to associate the identified NOG mutation with the syndromes of the studied Chinese family. Among all identified mutations of the proband, only one heterozygous G-to-T transversion c.163G > T at genomic position 54,671,747 of chromosome 17 was located in NOG, resulting in a substitution of aspartic acid to tyrosine at codon 55 (p.Asp55Tyr). Through literature search, we did not find the p.Asp55Tyr recorded in any database or on any previous publication. The evaluation of possible functional impacts revealed that p.Asp55Tyr was classified as a damaging mutation by multiple missense prediction tools (). Comparative amino acid sequence alignment of NOG protein across different species in mammals revealed that the novel p.Asp55Tyr mutation occurred at highly conserved position (). Furthermore, Sanger sequencing analysis identified p.Asp55Tyr in all the three affected family members (I-2, II-1, and II-4) while it was absent in the unaffected member (III-2) (). Therefore, p.Asp55Tyr co-segregated with the symptoms in the studied family. Additionally, we found that this variant was absent in 200 normal controls, suggesting that p.Asp55Tyr did not represent a rare polymorphism, but was a pathogenic mutation within this Chinese family.
The crystal structure of noggin protein (Protein Data Bank accession code 1M4U) was used to visualize the spatial arrangement of amino acids around the mutated residue. Modeling was performed in UCSF Chimera as stipulated in the previously established procedures (). Setting of all the parameters is described in . To better elucidate the mechanism by which the loss of function occurs, we mapped the identified p.Asp55Tyr (red) and all mutations previously reported in literature (green) to the structure () (). The disease-associated mutations are concentrated in three regions as previously reported: type I and type II receptor binding domains and the dimerization domain (, in circles) (). The aspartate residue (Asp55) is located at a distance from the BMP binding-site called the type I receptor-binding clip ( left panel, colored blue) and hence, it is unlikely that this mutation directly affects noggin’s binding affinity to type I site of BMP. The p.Asp55Tyr mutation reported in this study is located within the type II receptor binding region, surrounded by a group of known disease-associated mutations forming a mutational “hotspot” in the noggin protein. Closer look at this mutational hotspot reveals that the aspartate side chain strongly interacts with the positively charged Arg167 residue by hydrogen bonding ( right panel). In fact, among all the known mutations within the type II binding region, only four amino acid residues Glu48, Asp55, Arg167, and Arg204 were found to strongly interact with each other via hydrogen bonds between their side chains. Asp55 interacts with the Arg167 by three hydrogen bonds, Glu48 interacts with the Arg204 with four hydrogen bonds, and Tyr167 interacts with Glu48 with one hydrogen bond (). These four amino acid residues, two being positively and two being negatively charged, form a tight cluster and are very likely to hold the elbow-shaped BMP-interacting arm in position.
We replaced the aspartic acid residue with a tyrosine and computed the local structure using molecular modeling. Using the most probable conformation of the tyrosine residue (36.63% probability), we added hydrogens and analyzed the hydrogen bonds. All the three hydrogen bonds that were visualized between the aspartic acid and tyrosine 167 were abolished (); this indicated that p.Asp55Tyr was indeed a destabilizing mutation of the local protein folding. |
pmc-6499740-1 | We present the case of a 69-year-old woman who in May 2005 was diagnosed with adenocarcinoma of the rectum located 6 cm proximally from the anal verge. Concomitant diseases included type II diabetes and a long history of cigarette smoking. Using imaging diagnostics, the tumour was assessed as cT3N0M0. Initially, marker values were slightly elevated: CEA 7.1 ng/ml (normal range 0–3). The patient underwent preoperative irradiation of the pelvis using a three-field technique (X15 MeV photons; 5 fractions of 5 Gy/t up to a total of 25 Gy/t) followed by anterior resection of the rectum. Histopathology revealed very good response to radiotherapy with only few cancer glands invading maximally to muscularis propria (minimal residual disease) and displayed no nodal metastatic involvement. Postoperative period was complicated by anastomotic leakage—anastomosis was excised and sigmoidostomy was performed. After treatment, CEA concentration decreased to normal values. The patient entered oncological follow-up with routine screening for markers and computed tomography (CT) scans. In January 2008, CEA increased to 6.5 ng/ml, and reaching 17 ng/ml in September 2008.
In order to localise the site of recurrence, we performed abdominal and pelvic ultrasound (no pathological findings), bone scintigraphy (no pathological findings) and PET-CT, which presented an area of abnormal radiotracer density within the pancreas and (less suspicious) within the retroperitoneal space. We observed further increase of CEA to 18.7 ng/ml (September 2008) and a normal level of CA-19.9. Due to dissemination, patient was referred to chemotherapy according to the LF3 protocol (LV 36 mg, 5FU 756 mg administered for 2 days every 2 weeks). After the 7th course of chemotherapy, CEA concentration increased to 27.9 ng/ml and CA-19.9 level remained 0 IU/ml. We performed a control CT scan in which an irregular mass of approx. 30 × 30 mm was found between the corpus and tail of the pancreas (Fig. ). Other tissues and organs presented no abnormalities.
The patient was referred for surgery. In September 2009, she underwent distal resection of the pancreas with concomitant splenectomy. During surgery, no symptoms of intraperitoneal dissemination were found and the parapancreatic lymph nodes were unchanged. Recovery was uneventful. On macroscopic and microscopic examinations, a relatively well-delineated noncapsulated tumour was found. It consisted of atypical glands of relatively large size lined with high cylindrical epithelium. Glands’ lumina were filled with necrotic material reminding so called dirty necrosis as in colon cancer. Also, epithelium looked similar to intestinal lesion even though the colon cancer was changed by preoperative treatment. In order to confirm intestinal origin, immunohistochemistry was performed to reveal CK20 positivity and CK7 negativity as in colon cancer immunoprofile. In addition neighbouring parenchyma of the pancreas was unremarkable with reverse profile (CK7+, CK20-). The diagnosis of rectal adenocarcinoma metastases was made. The excision was complete (R0) (Figs. , , ). After surgery CEA fell from 30 ng/ml to normal values. The patient received adjuvant treatment according to XELOX protocol (oxiplatin 226 mg, xeloda 2 × 1500 mg per die over 14 days). Due to symptoms of neurotoxicity (dizziness, nausea, vomiting) only one course of chemotherapy was administered. According to the patient’s request the LF3 protocol was recommenced (LV 34 mg, 5FU 634 mg over 2 days). Altogether, between January and June 2010 she had been administered with 12 courses of chemotherapy. During treatment marker levels were low (fig. ). From the termination of adjuvant treatment until the end of February 2013 the patient was in routine follow-up. On the 20th of February 2013 PET-CT was performed due to an elevation of markers with no other symptoms of disease. It showed metabolically active infiltrates in the pre-sacral area, within the uterine wall and in the 11 thoracic vertebra and a tumour in the right lung. Bronchoscopy revealed an exofitic comedo infiltration closing the lumen of the 8th segment (pathology: rectal cancer metastasis). The patient received palliative treatment which ended in October 2014 due to progression (metastases to the CNS, thyroid and left suprarenal gland) with referral for symptom relief. |
pmc-6499842-1 | A 67-year-old man was admitted to our hospital with a history of dysphagia for 6 months. Upper gastrointestinal fiber endoscopy revealed a thoracic esophageal lesion. On histopathology, the biopsy specimen of the esophageal lesion revealed squamous cell carcinoma (SCC). Esophagography showed a localized lesion in the upper middle thoracic esophagus (Fig. ), and PET-CT showed no distant or local lymph node metastases (Fig. ). A preoperative diagnosis of upper thoracic esophageal squamous cell carcinoma (ESCC) of clinical stage T2N0M0 (stage IB) was made based on the TNM classification of the Union for International Cancer Control (UICC) []. He then underwent thoracoscopy-assisted esophagectomy and lymph node dissection, with reconstruction using a gastric tube through the retrosternal route. On histopathology, the resected specimen revealed well to moderately differentiated squamous cell carcinoma with invasion of the muscularis propria. According to the Japanese Classification of Esophageal Cancer, the tumor had an infiltrative type b growth pattern, with lymphatic (ly) 2, and venous invasion (v) 1. Intramural metastasis was not seen, and the resected margin was adequate. There were no metastases in the resected LNs, and the tumor was finally staged as T2N0M0 (stage II according to the Japanese Classification of Esophageal Cancer). The postoperative course was uneventful, and he was discharged without any complications. He received no adjuvant therapy in view of pathological stage T2N0M0 (stage IB) disease. He was regularly followed up monthly for 3 months after surgery and at 6 months thereafter. CT scanning was used to check for recurrences, twice a year.
At 3 years after surgery, a solitary metastatic lesion was detected by CT and PET-CT in the upper lobe of the left lung (Fig. ). A segmentectomy of the left lung was performed (Fig. ), followed by chemotherapy with CDDP and 5-FU. Histopathological examination of the resected specimen revealed moderately differentiated squamous cell carcinoma. The well-demarcated nodular lesion consisted of squamoid cancer cells proliferating in nests, with tumor necrosis. The pathologists suggested that the findings were more in favor of metastatic squamous cell carcinoma than primary lung cancer.
The year after the lung surgery, a metastatic lesion was detected on CT and PET-CT in the upper lobe of the right lung, invading the chest wall (Fig. ). This was managed with a partial lobectomy of the right lobe with local chest wall resection (Fig. ). The specimen revealed squamous cell carcinoma and contained lung tissue with the proliferation of severely atypical squamoid cells, arranged in nests. The histologic findings were similar to the previously resected lung specimen, and it was diagnosed as a metastasis from ESCC.
The year after right lobectomy, follow-up CT revealed multiple LN metastases in the mediastinum, right supraclavicular region, right axilla, and abdomen (Fig. ); PET-CT revealed increased uptake of FDG in the intra-abdominal LN, with a maximum standardized uptake value (SUVmax) of 6.1. The metastatic LNs were managed with chemoradiation to a dose of 50.4 Gy with concurrent CDDP and 5-FU. A partial response was achieved (Fig. ).
Locoregional LN metastases in the left cervical region were detected in the year after chemoradiation (Fig. ). As the patient had a good performance status, and the nodes were operable at ease, they were resected. (Fig. ). Histopathologic examination of the resected LN in the left neck and supraclavicular LNs revealed metastatic cancer cells in 9 of 16 LN. He then received additional chemoradiation to a dose of 50.0 Gy with CDDP and 5-FU.
The fifth recurrence occurred in the LNs of the mediastinum and right hilum, a year after the cervical nodes were treated (Fig. ). Chemotherapy was administered with an alternative regimen, combining nedaplatin and docetaxel. The follow-up CT scans after chemotherapy revealed complete response (Fig. ). At present, 11 years after esophagectomy, he is still alive with good disease control. |
pmc-6500019-1 | A 46-year-old never smoker Malagasy woman was referred by her family doctor to the emergency department due to dyspnoea with inspiratory stridor and inspiratory-expiratory wheezing with insidious onset over a 3-month period. The patient was treated for supposed asthma since 2 weeks without improvement. She had no fever, weight loss or night sweats. Physical examination revealed a heart rate of 96/min, a respiratory rate of 19/min, and an oxygen saturation of 89% on room air with normal chest auscultation. A non-tender mass was detected on the right side of her neck.
CT scans of the neck and thorax showed a large thyroid mass causing tracheal stenosis (Fig. a), and multiple cystic lesions with thin walls in both lungs (Fig. b). Cysts had a diffuse localisation, including the costophrenic recesses. Neither pulmonary nodules nor ground glass opacities were observed. Abdominal CT scan did not show any sign of renal angiomyolipoma.
Blood arterial gases showed mild hypoxemia (PaO2 82 mmHg). Laboratory investigations, including renal function, liver function tests, C-reactive protein, thyroid function tests, complete blood cell counts, and serum IgG4 levels were all within normal limits. HIV and immunological tests (anti-Ro/SSA and anti-La/SSB antibodies, rheumatoid factor and thyroid-stimulating hormone (TSH) receptor antibody) were negative. Plasma levels of vascular endothelial growth factor-D (VEGF-D) were low (347 pg/mL; normal range 0–450 pg/mL). Electrocardiogram (ECG) tracing and complete pulmonary function testing were normal (forced expiratory volume in 1 s - FEV1 94%, total lung capacity – TLC of 95% of predicted and normal carbon monoxide diffusing capacity - DLCO).
Surgical removal of the thyroid mass with subtotal thyroidectomy, tracheal segment (3.5 cm) resection and multiple adenectomies were performed (Fig. ). Microscopic study revealed extensive infiltration of all lymph nodes and the thyroid with partial replacement of follicular parenchyma by a fibro-inflammatory process of mixed cellularity, rich in histiocytes (Fig. a). The latter exhibited epithelioid to xanthomatous morphology and formed ill-defined clusters or confluent sheets without granulomatous pattern. An important fraction of the histiocytic population showed emperipolesis of neutrophil granulocytes and lymphocytes (Fig. b). Immunohistochemistry revealed co-expression of the macrophage-related epitope CD68 along with S100 protein, in the absence of CD1a, thereby identifying the histiocytic elements as of non-Langerhans lineage (Fig.a, b and c). Remarkably, storiforme fibrosis with signs of vasculitis was also observed and immuno-phenotyping of the infiltrate revealed a substantial participation of IgG4-bearing plasma cells. While their absolute density reached up to 50 per high power field, the IgG4:IgG ratio did not exceed 20% (Fig.d). Histological examination of the tissue biopsies for the identification of infectious organisms using several stainings for pathogens were negative. Based on these findings, a histological diagnosis of RDD was made.
Following surgery dyspnoea disappeared indicating that it was related to tracheal compression. The patient was asymptomatic in the absence of any specific treatment; clinical, functional lung testing and radiological follow up 4 years after surgery did not reveal any disease activity or progression underlining the excellent prognosis of the disease after resection. |
pmc-6500020-1 | A 24-year-old married Arab woman had been admitted to a local health center 2 months prior to referral to our urology department. She had been hospitalized there four times in 1 year for acute pyelonephritis. The fourth episode raised the suspicion for an underlying problem and justified her referral to our urology department after management of the acute pyelonephritis.
On admission, she complained of ascending left-sided flank pain during micturition but did not have dysuria or hematuria. She also had a history of frequent urinary tract infections (UTIs) as a young adult.
She was perfectly asymptomatic on the right side. A physical examination was normal. Her temperature was 37.4 °C, her blood pressure was 128/84 mmHg, and her pulse rate was regular at 76 beats per minute. Laboratory tests were normal; in particular, a urine examination showed no leukocyturia or bacteriuria.
She underwent an abdominal ultrasound which showed an asymmetric size of the kidneys and a bilateral chronic pyelonephritis aspect. Her right kidney measured 10 cm while the left measured 12 cm.
A voiding cystourethrography (VCUG) was performed and showed grade IV VUR on the left side and grade I VUR on the right (Figs. and ).
An abdominal and pelvic computed tomography (CT) scan detected a left completely duplicated collecting system with hydroureteronephrosis and poor opacification of the upper pole moiety. In addition, the parenchyma of the upper pole moiety was atrophied with secretory and excretory delay. In association with VCUG findings, it appeared that the refluxing ureter was the one that drains the upper pole moiety and inserts lower into the bladder. On the right, a duplex collecting system was detected with hypotonic calyces, pelvis, and ureter of the upper pole moiety. An atrophic parenchyma and poor opacification of the upper pole moiety was also detected (Figs. and ). Renal scintigraphy was not available.
We carried out a left heminephrectomy because of the poor functioning of the upper pole moiety based on imaging findings associated with recurrent UTIs (Fig. ). On the right side she underwent dextranomer/hyaluronic acid (Deflux®) injections. Dextranomer/hyaluronic acid (Deflux®) was injected submucosally below the ureteral orifice at the 6 o’clock position to create a prominent bulge and raise the distal ureter and ureteral orifice.
A year after the surgery she has no complaints. The symptoms are completely resolved. Biological and radiological follow-up is unremarkable. A timeline of the case is presented in Figure . |
pmc-6500033-1 | A forty-one-year old female admitted to our hospital with chief complain of Raynaud’s phenomenon for 2 years, and weakness of four extremities for about 2 months. She had morning stiffness of both hands and the symptoms were relieved after 20–30 min of repeated rubbing. No joint pain, fever, oral ulceration, alopecia and rash were noticed. In addition, 2 months before beginning the admission, the patient felt weakness on her both arms and legs, and the weakness aggravated progressively. Difficulties in squatting or standing up, as well as hair combination were noticed. She also complained about muscle tenderness without any difficulty in breathing or swallowing. She was diagnosed as hypothyroid myopathy in a local hospital and levothyroxine was taken. However, her weakness was not improved, accordingly, she was transferred to our department.
The patient’s past medical history was remarkable for left glaucoma with retinal detachment and impaired visual sight in 2015. Besides, she was diagnosed as SWS since childhood. She was also diagnosed as hypothyroidism, and regular levothyroxine replacement was given for several years as well.
Physical examination revealed that the vital sign is stable. 12 cm × 12 cm red patches were visible on her left side, and the boundary was unclear as well. Thyroid nodules and swelling were not palpated. Breathing sounds in both lungs were clear. Proximal muscle strength of her both arms was in level-4 (the UK Medical Research Council criteria), and strength of both proximal legs was in level-3 as well. The distal strengths of her arms and legs were normal, and muscle tenderness was quite obvious in her both arms and legs. Other neurological examinations were not significant.
Laboratory examinations revealed positive anti-nuclear antibody with titer of 1:320 (particle pattern), positive anti-recombinant RO-52 (+++), positive weakly anti-nucleosome antibody (+), and negative anti-neutrophil cytoplasmic antibodies (ANCA). Level of serum creatine kinase (CK) was 11,183 U/L (normal range: 26–140), and myoglobin was 1916 ng/ml (normal range: 25–58). Other chemical examinations revealed that alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were elevated. Thyroid function was normal with 278 IU/ml (normal range:0–115) of elevated anti- thyroglobulin (TG). Electromyography (EMG) showed typical myopathic findings with predominantly proximal muscle weakness. Cranial magnetic resonance imaging (MRI) showed increased anterior chamber of left eye, skin thickening of left facial and abnormal signals of interior wall of left eye, as well as upper and lower recuts. Intracranial brain parenchyma was normal and magnetic resonance angiography (MRA) was not remarkable as well.
Inflammatory myopathy was diagnosed based on the clinical features and laboratory results. Intravenous methylprednisolone (MP (80 mg/d) was administrated and methotrexate (10 mg/week) was intramuscularly injected. The patient’s muscle strength gradually improved, and CK dramatically decreased to 2800 U/L. After 2 weeks, methylprednisolone was gradually tapered to 40 mg/d. As the CK was quite high, intravenous cyclophosphamide was added with a total amount of 6 g.
The patient was discharged with oral MP tapering and methotrexate (MTX) (7.5 mg/week) for maintenance. She was regularly followed-up at our clinic as well. For about half a year, the muscle strength of her arms and legs returned to normal status, and CK was also within normal range. |
pmc-6500582-1 | A 54-year-old Caucasian man was referred to our hospital for management of sarcoidosis. This was found in investigations for a 2-year history of progressive right upper quadrant abdominal pain. He underwent computed tomography (CT) of his abdomen and pelvis, which revealed significant findings of diffuse lymphadenopathy. CT of his chest demonstrated bilateral hilar and mediastinal lymphadenopathy concerning for lymphoma. The patient underwent thoracic lymph node biopsy, which revealed noncaseating granulomas, consistent with sarcoidosis.
His abdominal pain was initially occurring every few days and was sharp in nature. It was located along the right costal margin. His pain progressed to daily episodes and eventually constant discomfort. The pain began to radiate around to his back along the tenth rib. Over the course of 1 year, his pain became neuropathic with symptoms of allodynia and intermittent, shock-like pain. His pain also migrated to his T7–T11 dermatomes. He had no other symptoms.
The patient’s past medical history was significant for an 8-year history of type 2 diabetes mellitus without any known complications, as well as dyslipidemia, asthma, osteoarthritis, bilateral knee replacements, and a cholecystectomy. His medications at the initial visit included metformin, gliclazide, liraglutide, hydrochlorothiazide, trandolapril, aspirin, celecoxib, tramadol/acetaminophen, atorvastatin, and inhaled budesonide/formoterol. His family history included premature cardiovascular disease in both of his parents. One brother had lung cancer and his sister had ovarian cancer. He is a lifelong nonsmoker and consumes alcohol socially about once per month. He is a medical administrator with the military and had traveled extensively in the past with the military but had only visited resorts in Central America over the last 2 years. He has a parrot at home and no other animal contacts.
On initial examination, his blood pressure was 120/76 mmHg, and his heart rate was 89 beats/min and regular. He had no jugular venous distention. His heart sounds were normal with no extra sounds or murmurs. His lungs were clear to auscultation. His abdomen was soft but mildly tender on palpation in the right upper quadrant. His liver edge was palpable about 2 cm below the costal margin and was smooth. He did not have any signs of splenomegaly on examination. His extraocular movements were normal, as were the results of the rest of his cranial nerve testing. His muscle bulk and tone were normal. His strength was 5/5 on Medical Research Council grading throughout. His reflexes were 2+ bilaterally. He had no evidence of ataxia, and his gait was normal. His plantar reflexes were downgoing bilaterally, and no pronator drift was present. His sensation was normal initially, but on serial examinations over the next year, he developed allodynia over the right-sided T7–T11 dermatomes with pain to light touch. He also had decreased sensation to pinprick and light touch in this area.
Biochemical and hematologic serum test results were within normal limits (Table ). His C-reactive protein was normal at 4.70 mg/L. His 24-h urine calcium was elevated at 12.5 mmol/24 h (normal range, 0.0–7.4 mmol/24 h). His electrocardiogram (ECG) was normal. Results of his pulmonary function testing were normal with a forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio of 76%, FEV1 89% predicted, FVC 93% predicted, total lung capacity 99% predicted, and diffusing capacity of the lungs for carbon monoxide 125% predicted.
Magnetic resonance imaging (MRI) of his spine revealed abnormal thickening and enhancement of paravertebral soft tissues along the right intercostal spaces that extended from T7 to T12 (Figs. and ). There was enhancement of the right thoracic nerve roots from T5 to T10. This was in keeping with neurosarcoidosis. MRI of the patient’s head did not reveal any evidence of sarcoidosis involving his brain. Cerebrospinal fluid (CSF) analysis revealed 3 × 106 white blood cells/L (100% lymphocytes), 1 × 106 red blood cells/L, total protein 0.47 g/L, and glucose 6.65 mmol/L.
After MRI of the patient’s spine, he was started on prednisone 75 mg daily. Gabapentin was initiated. There was minimal change in his symptoms after 3 weeks. Azathioprine was added (titrated up to 225 mg daily) over the next 6 months while prednisone was tapered. His 24-h urine calcium normalized, but he did not experience significant changes in his neuropathic pain. Mycophenolate mofetil and infliximab (every 8 weeks) were then initiated, and azathioprine was stopped. However, after four doses of infliximab, he noticed an overall decrease in his neuropathic pain. |
pmc-6500600-1 | A 60-year-old man with advanced bilateral open-angle glaucoma for 3 years, not controlled with maximum medical therapy in the left eye, underwent phacoemulsification in the left eye in 2014. The medical records did not register coagulation disorders and the patient denied to have taken antiplatelet medicine or anticoagulants.
Before the surgery, the uncorrected visual acuity (UCVA) was 2.5 and 1.3 LogMAR in the right and left eye, respectively. The intraocular pressure was 12mmHg in the right eye and 26mmHg in the left eye with maximum medical therapy. On Humphrey Field Analyzer (HFA) 24-2 automated perimetry mean deviation (MD) was -16.92 in the left eye, pachymetry was 517 microns in the right eye and 492 microns in the left eye, and the number of central endothelial cells was 2127 cells/mm2 in the right eye and 1312 cells/mm2 in the left eye.
Ab interno canaloplasty was performed routinely in the left eye by a glaucoma specialist. The temporary corneal incision was made at hour 9 and another lateral incision was made at hour 2 to introduce the iTrack catheter (iTrack-250A; iScience Interventional, Menlo Park, CA, USA). Sodium hyaluronate was injected (Healon GV; Abbott Medical Optics, Santa Ana, CA, USA) in the anterior chamber. Gonioscopy was used (AVG; Surgical Gonio Lens, Volk Alcon, Mentor, OH, USA) for goniotomy with Kahook dual blade (KDB; New World Medical, Rancho Cucamonga, CA, USA), and by using tying forceps (Intraocular Tying Forceps, 23G 4-1891, Rumex, USA) the catheter was pushed circumferentially through 360°, by applying two viscoelastic clicks per hour when removing it.
The procedure was performed correctly; however, during the viscodilation of the Schlemm canal with sodium hyaluronate, a small hemorrhage was observed with viscoelastic related to the Descemet membrane detachment. The paralumbar extension was 3.0 mm and radial extension was 2.0 mm between hours 4 and6 in peripheral inferonasal quadrant. At first we opted for observation because the injury did not compromise the visual axis and the size of the detachment was not large enough to indicate a surgical procedure immediately ().
A serial control with anterior segment OCT (Visante, Model 1000, Carl Zeiss Meditec, Dublin CA, USA) has been done to follow the thickness; the initial thickness of intrastromal hemorrhage was 0.6mm, and at the first week it was 0.51mm, at the first month 0.42mm, and at the second month 0.28 mm and third month 0.03 mm. The examination evidenced presence of blood in the peripheral inferonasal quadrant of the pre-Descemet area at hours 4-6 (Figures , , , , and ).
Considering the extension of the detachment, a conservative management was decided, monitoring the progressive reabsorption of the hemorrhage and viscoelastic, which progressively occurred (Figures and ).
The intraocular pressure levels remained lower than 21mmHg in the early postoperative period with glaucoma medications; 3 months after the surgery the intraocular pressure was 18mmHg with 3 antiglaucoma medications. The uncorrected visual acuity (UCVA) showed a significant improvement from 1.30 in the preoperative period to 0.8 LogMAR in the left eye after 3 months of monitoring (). Final BCVA was 0.6 LogMAR.
The number of central endothelial cells registered a small decrease from 2,127 to 1,809 cells/mm2 in the third month with a 14.9% loss. Final pachymetry was 553 microns in the left eye, showing an increase of corneal thickness of 12.39% in the third month.
According to Hodapp classification, the visual field defect 10-2, stimulus III, and white-on-white of the left eye indicated a stable advanced stage glaucoma with a MD of -31.4.
Three months after the surgery, the Descemet membrane detachment with intrastromal hematoma completely recovered; the membrane was reattached correctly () and remained that way during the monitoring with the transparent cornea along with no visual consequences. |
pmc-6500601-1 | A 51-year-old man was referred to our hospital for treatment of hemoptysis. One week before, he presented with coughing up of approximately 1 cup of bright red blood, which was diagnosed as active pulmonary tuberculosis. He had poorly controlled diabetes mellitus.
When he arrived at our hospital, hemodynamic status was stable, and there were no abnormal signs or symptoms, except for low-grade fever and mildly elevated C-reactive protein. Contrast-enhanced computed tomography (CT) revealed a 7 mm round pseudoaneurysm within a cavitary lesion in the left upper lobe of the lung (). The pseudoaneurysm was thought to originate from a branch of the left superior segmental pulmonary artery (). He was diagnosed with Rasmussen's aneurysm and underwent interventional treatment.
A 5-Fr catheter (SHK, Terumo Clinical Supply, Gifu, Japan) was advanced to the left bronchial artery. A left bronchial angiography depicted the aneurysm via a shunt from the bronchial to the pulmonary artery. However, we could not advance the microcatheter to a more peripheral branch near the lesion, because the anastomosis was small and tortuous (). Eventually, subintimal dissection developed in the left bronchial artery and we failed to embolize the aneurysm via the left bronchial artery.
Subsequently, a 5-Fr guiding catheter (Envoy, Codman Neurovascular, Raynham, Massachusetts, USA) was advanced to the left main pulmonary artery. Left main and left superior segmental pulmonary angiography could not depict the aneurysm. However, we noted an abrupt disappearance of the left superior segmental pulmonary artery, which indicated retrograde flow from the bronchial to the pulmonary artery. The tapering was in the branch that was suspected as the parent artery of the aneurysm on CT (). Based on these findings, we were able to identify the parent artery and reach the aneurysm using the microcatheter.
Two microcatheters were placed in the aneurysm and pulmonary artery proximal to the aneurysm. A 1.7-Fr microcatheter (Echelon, ev3, Irvine, California, USA) and a 1.9-Fr microcatheter (Carnelian Marvel, Tokai Medical Products, Aichi, Japan) were inserted in parallel through a guiding catheter. The 1.7-Fr microcatheter was positioned proximal to the aneurysm, whereas the 1.9-Fr microcatheter was advanced into the aneurysm. Because we decided to choose NBCA for embolization, we first performed proximal superior segmental pulmonary artery embolization proximal to the aneurysm using the 1.7-Fr microcatheter, with 3 coils measuring 3 mm × 6 cm, 2.5 mm × 6 cm, and 2 mm × 8 cm (ED COIL10 ExtraSoft Type R, Kaneka Medix, Osaka, Japan) to prevent unintended reflux of the NBCA. Thereafter, a 0.8 mL mixture of NBCA and iodized oil (Lipiodol, Guerbet Japan, Tokyo, Japan) (NBCA:Lipiodol = 1:3) was retrogradely injected into the aneurysm through the remaining 1.9-Fr microcatheter. The aneurysm was filled with the mixture of the NBCA and iodized oil, but the feeding artery could not be embolized retrogradely (). Although postembolization bronchial angiography could not be performed due to the subintimal injury in the left bronchial artery, postembolization pulmonary angiography did not show the residual aneurysm ().
After treatment, he remained stable without further hemoptysis, and there were no other side effects or complications. Follow-up CT performed 2 months later confirmed successful embolization of the aneurysm (). |
pmc-6500605-1 | A man aged 41 years was transferred to our center at Shiraz University of Medical Sciences, Iran, sustaining gunshot wound to his back and abdomen. In terms of past medical history, he was a rural man with poor healthcare and traditional drug addict (flexible dosing) with no family history of cancer. There was not any history of weight loss, anorexia, and change in bowel habit. Although he was hemodynamically stable, initial evaluation showed retroperitoneal hematoma (about 500 cc blood) with expansion from zone III to zone I and also S2 vertebral fracture.
At the laparotomy, patchy necrosis of rectum was detected and short segmental resection (5.5 cm in length) was performed. Although, there was not any gross evidence of abnormal finding during operation, as a rule in our department any specimen removed from human body should be sent to pathology examination and the specimen underwent pathologic assessment.
Grossly there was edema, multifocal necrosis, and a small polypoid firm lesion measuring 1x1x0.5 cm near one margin, histologically showing well differentiated adenocarcinoma, hard to believe (). Microscopic tumor extension was limited to submucosa (T1), signed out as stage I (). |
pmc-6500608-1 | A 51-year-old woman with PRS presented with an 8-year history of binocular horizontal diplopia on right lateral gaze exacerbated during exercise. Her diplopia on exertion would resolve shortly after cessation of exercise while cooling off. The patient denied eye pain, floaters, photopsia, decreased vision, paresthesias, or motor deficits of the extremities. The patient's history of PRS was characterized as progressive left-sided facial atrophy for a period of 10 years following infection with herpes zoster and postherpetic neuralgia in the distribution of the ophthalmic division (V1) of the trigeminal nerve. Examination showed atrophy involving the left temporal region and alopecia localized to the left frontal parietal region, corresponding with V1. There was minimal hyperpigmentation of skin over the left vivum dermatome and a linear hypopigmented scar (coup de sabre) was observed. On neurologic examination, speech was fluent without dysarthria or aphasia, and cognitive functions were intact. Tongue and uvula were midline. Motor examination showed normal tone, no evidence of drift, and 5/5 strength bilaterally. Coordination and gait were intact. Deep tendon reflexes were 2+ bilaterally and plantar responses were flexor. Sensory examination was normal and intact to light touch and pin prick testing. The patient's past medical history was significant for Hashimoto's thyroiditis, migraine headaches, and recurrent outbreaks of herpes simplex labialis. Medications included levothyroxine 50 mcg daily. Family history was significant solely for migraines in the patient's sister.
On ophthalmologic examination, best-corrected visual acuity was 20/20 in both eyes. Applanation tonometry measured intraocular pressures of 12 in both the right and the left eyes. Fundus examination was normal appearing without evidence of pallor or edema. Pupils were equal and reactive to light with no afferent pupillary defects. Color vision assessment on Ishihara plate testing showed 15/15 OD and 13/15 OS. Ocular motility examination was significant for 30-degree limited adduction of the left eye on right lateral gaze.
Autoimmune panel was positive for antinuclear antibody (ANA) (1:40 speckled pattern, normal range <1:40) and negative for beta 2 glycoprotein and cardiolipin immunoglobulins (IgA, IgG, and IgM). Vitamin B12 and Vitamin E levels were within normal limits. Magnetic resonance imaging (MRI) of the brain showed multiple white matter lesions including the left frontal lobe, left parieto-occipital area, and periventricular areas of the left frontal and left posterior horns of the lateral ventricles (Figures –). In addition, FLAIR/T2 hyperintensity of the midbrain region corresponding to the area of the MLF was seen (). MRI of the orbits () showed normal positioning of the globes bilaterally without evidence of proptosis or extraocular muscle fibrosis or atrophy. MRI of the spinal cord showed no evidence of spinal lesions.
Given recurrent outbreaks of herpes simplex labialis, the patient was started on valacyclovir 500 mg PO BID. On follow-up 3 months later, the patient indicated that her heat-induced diplopia was completely resolved. Ocular motility examination was significantly improved with less than 10-degree limited adduction of the left eye on right lateral gaze. |
pmc-6500615-1 | An 82-year-old female with a history of asthma, gastroesophageal reflux disease, diverticulitis, ulcerative colitis, prior left hip replacement, and cholecystectomy presented to the ED with a 3-day history of right lower quadrant pain with associated nausea, nonbloody vomiting, and diarrhea. She was also complaining of a cough and back pain at the time of evaluation. She admitted to having a fall 3 weeks prior. Further review of systems was negative.
Vital signs were blood pressure of 155/80 mmHg, pulse of 74 beats per minute, respirations of 18, and temperature of 36.7°C. Examination revealed a soft abdomen with right lower quadrant tenderness to palpation without evidence of an inguinal mass or erythema. Lab analysis was essentially normal. There was no leukocytosis. A CT scan of her abdomen was obtained due to her back pain and RLQ pain. The CT was interpreted by radiology as a right femoral hernia containing an inflamed appendix. Refer to Figures and for CT images.
The patient was treated operatively with laparoscopic appendectomy and by McVay hernia repair. No mesh was used during the repair of the hernia. The postoperative diagnoses were more complicated than what was visualized by radiology on the CT and included a Pantaloon hernia, a femoral hernia, and an Amyand's hernia containing an early, nonperforated appendicitis. The patient had no intraoperative or postoperative complications with the exception of pain, classified as Clavien-Dindo grade 1. On postoperative day 2, she was discharged to the skilled nursing facility where she resided. The patient's Charlson Comorbidity Index was calculated and her 10-year survival was estimated to be 53%. |
pmc-6500615-2 | A 93-year-old female with a history of left ventricular hypertrophy, atrial fibrillation, hypertension, and no prior abdominal surgeries presented to the emergency department with dull, constant right lower quadrant pain for the past week. She saw her primary care physician who ordered an outpatient CT for possible hernia. The CT was concerning for appendicitis with adjacent abscess and hernia, so the patient was referred to the ED for further management. In the ED, she admitted to subjective fevers and melena at home. Review of systems revealed no other symptoms.
Vital signs were blood pressure of 119/47 mmHg, pulse of 91 beats per minute, respirations of 16 per minute, temperature of 36.4°C, and oxygen saturation of 96% on room air. Examination revealed a soft abdomen with right lower quadrant tenderness to palpation and a nonreducible, erythematous groin mass. Lab analysis revealed a leukocytosis of 12.7 K/uL with a predominance of neutrophils. Radiology interpretation of the outpatient CT showed a right inguinal hernia containing vermiform appendix with adjacent abscess measuring 4.3 cm x 3.5 cm transversely. Refer to for CT imaging.
The patient underwent surgical management with appendectomy and McVay hernia repair. The appendix and adjacent abscess were accessed by way of the groin through the hernia. Intraoperatively, the hernia was found to be below the inguinal ligament in the femoral space. The abscess was drained, and the appendix was removed. The hernia was repaired without the use of mesh. The postoperative diagnosis was De Garengeot's hernia. The patient underwent no complications in the operating room or postoperatively with the exception of pain, Clavien-Dindo classification grade 1. She was discharged to home on postoperative day 3. Using the Charlson Comorbidity Index, her 10-year survival was estimated to be 21%. |
pmc-6500617-1 | A healthy 29-year-old G1P0 at 39w5d was admitted for labor induction secondary to decreased fetal movement and indeterminate fetal heart rate tracing. She has no past medical (significant for baseline anemia (hemoglobin of 9.0) during pregnancy) or surgical history. Her labor induction involved a single dosage of 25 mcg of Misoprostol per vagina followed by cervical Foley insertion with Oxytocin administration for approximately 30 hours. She underwent a primary cesarean delivery for Category II fetal heart rate tracing and arrest of dilation at 5 centimeters. The cesarean delivery was performed without complication.
On postoperative day one, the patient was febrile (38.8°C), hypotensive (80-95/40-55), and tachycardic (120-140). The patient was diagnosed with sepsis from endomyometritis and was started on intravenous ampicillin, gentamycin, and clindamycin. Sepsis workup included blood and urine cultures, laboratory studies, and chest x-ray. Laboratory studies indicated hemoglobin of 7.0 and she underwent a transfusion of two units of packed red blood cells with an appropriate rise to hemoglobin of 9.3. On postoperative day two the patient was hemodynamically stable but still remained febrile (T Max 39.3°C). The urine culture and blood cultures were positive for Escherichia coli. Infectious disease (ID) consultation recommended a new antibiotic regimen of intravenous piperacillin-tazobactam. Sensitivities of the organism demonstrated a multidrug resistant (MDR) Escherichia coli and the regimen was changed to intravenous meropenem. On postoperative day three, a transabdominal ultrasound showed no retained products of conception, a thin endometrial stripe, and no evidence of endometrial abscess. Computed Tomography (CT) scan of the Abdomen and Pelvis was performed later that day and demonstrated a 2.6 x 2.5 cm defect by the cesarean delivery hysterotomy below the fascia with fluid, small amount of complex abdominopelvic ascites with few gas bubbles. No urinary tract pathology was evident on imaging.
ID recommended additional oral metronidazole and heparin therapeutic anticoagulation for concerns of septic pelvic thrombophlebitis. The patient continued to be febrile the next 24 hours and repeat CT imaging demonstrated the 2.6 cm wound defect with a new abscess measuring 3.3 x 0.9 along the anterior aspect of the uterus and in the rectouterine space (). The uterine endometrium appeared heterogeneous with one foci of gas. The oral metronidazole was discontinued and vancomycin was started. The patient continued to have fevers for the next 48 hours and was counseled for hysterectomy. The patient consented to the procedure and underwent an exploratory laparotomy, abdominal washout, total abdominal hysterectomy, bilateral salpingectomy, and Jackson Pratt drain placement on postoperative day nine after her initial primary cesarean section. Intraoperatively, there was purulent ascites with a severely necrotic uterus.
After the hysterectomy, the patient remained on meropenem and vancomycin. Cultures obtained from surgery grew primarily Escherichia coli and Enterococcus faecalis. After the hysterectomy, the bacteremia resolved, but fevers continued through postoperative day five after hysterectomy. CT imaging performed showed two pelvic abscesses that were ultrasound-guided drained with pigtail placement. The patient remained afebrile with several consecutive negative blood cultures. The drain was removed and the patient was discharged on postoperative day eleven on Bactrim and Augmentin for one week. At her postoperative check, she was doing well and at her six-week visit she had healed completely. |
pmc-6500621-1 | A 26-year-old female, period of gestation of 35 weeks and 6 days into her third pregnancy, presented with contraction pain which was increased in intensity and frequency. She denied any leaking liquor nor show. Fetal movements were well felt. She claimed that she had fever, headache, sore throat, and dry cough for one-day duration. She denied any travelling or any contact with live poultry. She also had no history of dysuria and frequency. Her booking visit was at 9th week of gestation and all routine antenatal tests were negative. Latest scan was done at 33-week follow-up and all parameters were corresponding to gestational age.
On physical examination, she appeared alert, conscious, with no tachypnea and no signs of dehydration. She was afebrile, with no cervical lymph nodes and tonsillar enlargement. The lungs were clear. She had tachycardia up to 110/min and blood pressure was 105/57 mmHg. The abdominal findings corresponded to gestational age, single fetus, longitudinal lie, and cephalic presentation with good fetal heart rate. The estimated fetal weight was 2 to 2.2 kg. The vaginal examination noted that os was closed. The ultrasound examination was repeated and it corresponded to respective gestation. The urine dip stick was suggestive of urinary tract infection. The urine specimen was sent for culture and sensitivity (C&S) before starting the antibiotics.
She was observed in the maternity ward. However, the patient was noted to be febrile with temperature of 39°C, tachycardia, and low blood pressure 80/50mmHg on next day leading to septic shock. Her blood pressure was maintained by intravenous noradrenaline infusion. A septic workup was done and initial resuscitative measures were performed. The blood test results came back with white cell count of 15.34 x 109/L and C-reactive protein level of 365mg/L. She went into active phase of labour at the same time.
Multidisciplinary input from anaesthetist for ICU backup, physician, and infectious disease teams was obtained, led by obstetric consultant shared care. The arterial blood gas showed metabolic acidosis. Her condition worsened as she became restless and breathless even with 2L/min oxygen under nasal prong. Four hours in labour, it was noted that the progress of labour was unsatisfactory with features of fetal distress. A decision was made to deliver by caesarean section in collaboration with anaesthetist and ICU team. An alive, female, 2.61 kg baby with Apgar score of 5 in 1 minute, 7 in 5 minutes and 8 in 10 minutes, was delivered and estimated blood loss was about 700 ml. A placental swab was taken for C & S. The anaesthetist noted on lungs auscultation that air entry at the left lower zone and a portable chest X- ray was ordered. The chest X-ray was reported as slight basal lobe collapse at left lobe with reactive pleural effusion (Figures and ). Tamiflu was started and she was diagnosed with Acute Respiratory Distress Syndrome (ARDS). The baby was admitted to the nursery for late prematurity with presumed sepsis. Antibiotic treatment was given. The placenta swab culture result came back as sterile; still the baby needed photo therapy as neonatal jaundice arose.
The patient was extubated after one day but continued support with Venturi mask 50% and 1.5L/min of oxygen. Once stable, she was transferred to High Dependency Unit and continued monitoring there. The throat swab was reported as influenza A positive and the message was relayed to both Infectious Diseases and Paediatric team. The recommendation was to continue tablet Tamiflu (oseltamivir phosphate) for one week. Universal precaution and isolation of the patient were followed. The symptoms subsided with the treatment. The patient and baby were discharged on the fifth day postoperatively without complications. |
pmc-6500634-1 | A 69-year-old female underwent placement of RMUS in May 2014 for SUI by a surgeon from another institution. She developed de novo left groin/inner thigh pain, vaginal pain, and abdominal pain at the site of left sling arm and de novo overactive bladder and dysfunctional voiding. After follow-up and discussion with her original surgeon, they decided to proceed with a sling incision six months from her sling placement. After the sling revision, her pain and urinary symptoms did not improve, and she was self-referred to our institution for evaluation.
After a thorough evaluation that included examination, cystoscopy, labs, CT scan, and Urodynamics (UDS) that revealed pertinent findings of trigger point tenderness at the left suprapubic trocar incision site and vaginally in the left levator muscles, the left trocar incision site was unusually more superior and lateral than is typically found on examination, and UDS findings demonstrated urodynamic stress incontinence and bladder outflow obstruction. After extensive counseling, patient underwent transvaginal and suprapubic removal of the remaining left retropubic arm and remaining suburethral portion of the sling. |
pmc-6500640-1 | Here we describe, a 72-year-old female with a history of hypothyroidism, hyperlipidemia, hypertension, and 50 pack years of smoking, who presented to an outside facility with a 30-pound weight loss, severe nausea, emesis, mild imbalance which graduated to bedbound instability, and involuntary body “shakes” progressing over 6 months. Initial investigations at an outside facility, including contrast enhanced-MRI imaging of the entire neuroaxis, EEG, colonoscopy, and basic hematologic and chemistry panels, were all normal. The only initial abnormal findings were as follows: esophagogastroduodenoscopy (EGD) revealed possible gastritis, thyroid stimulating hormone was mildly elevated (9 U/mL), and anti-thyroid peroxidase antibody was elevated at 50 mg/L. She was evaluated by a psychiatrist who prescribed sertraline, as well as recommended relaxation techniques; however, her family requested further evaluation, and she was transferred to our institution. On physical exam, she had disorganized high amplitude conjugate horizontal movements of her eyes which persisted with eye closure, severe truncal ataxia that prevented her from sitting up without support, and distinct abdominal myoclonus. Otherwise, her neurological exam, including detailed mental status exam testing, was unremarkable.
Symptomatic and empiric therapy with lorazepam, levetiracetam, and a 5-day course of high dose IV methylprednisolone was immediately initiated. Further work-up revealed a lymphocytic pleocytosis in her cerebrospinal fluid (CSF) of 25 WBCs, with an otherwise unremarkable profile. Cytology was negative for malignancy and flow cytometry demonstrated a T cell dominant inflammatory process believed to be reactive. Paraneoplastic panel was negative in the CSF; however, voltage-gated potassium channel antibodies (VGKC) were detected in her serum (0.05 nmol/L; normal <0.02 nmol/L). Notably, the CSF VGKC assay was not yet available in our laboratory at the time of this patient's evaluation. Review of outside duodenal biopsy slides obtained during EGD was consistent with acute H. Pylori infection.
Computed tomography (CT) of the chest was normal. A subtle pancreatic duct cut-off sign was noted on abdominal CT, suggestive of a pancreatic mass (). Subsequent MRI and endoscopic ultrasound-guided fine needle biopsy confirmed a ductal adenocarcinoma of the body of the pancreas (). The patient underwent laparoscopic distal pancreatectomy and splenectomy, and a ductal adenocarcinoma, histologic grade 3/4 measuring 1.8 x 1.7 x 1.5 cm, in the body of the pancreas was removed. Negative operative margins were achieved, and all resected lymph nodes were negative for metastasis. Acutely following surgical resection, she experienced marked resolution of OMS symptoms. Upon taper and discontinuation of levetiracetam, some of her initial symptoms returned, including slight tremor and gait instability; however, the opsoclonus did not recur. Repeat serum paraneoplastic panel demonstrated VGKC normalization. She was initiated on single agent cisplatin-based chemotherapy and appeared to be responding well; however, she unfortunately died 7 months later, due to recurrent lung infections and pulmonary compromise. |
pmc-6500649-1 | A 53-year-old female presented with gradually progressive diminution of vision in her left eye for 2 months. She had a history of diabetes mellitus for 20 years for which she is taking insulin. Her most recent HbA1C was 7.5%. She had no history of hypertension or renal problems. She had no past ocular history. Examination revealed a corrected distance visual acuity (CDVA) of 20/40 in her right eye and 20/100 in the left. Anterior segment examination showed nuclear sclerosis in both eyes. Posterior segment examination revealed intraretinal hemorrhages in all 4 quadrants indicating severe nonproliferative diabetic retinopathy in both eyes with clinically significant macular edema in the left eye confirmed by fluorescein angiography (). Spectral domain optical coherence tomography (OCT) of the macula was done and revealed multiple cystic spaces, mild subfoveal neurosensory detachment, and diffuse retinal thickening with a central subfield macular thickness of 332 μm in the left eye (). The right eye showed only few cystic spaces with minimal thickening. OCTA (Optovue, Inc., Fremont, CA, USA) was done in both eyes and showed areas of capillary nonperfusion in the superficial capillary plexus (SCP) of the maculae of both eyes (Figures and ). Three monthly intravitreal bevacizumab injections were done to treat the macular edema in the left eye. One month following the last intravitreal injection, CDVA improved to 20/60 in the left eye and was stable in the right eye. OCT showed improvement of the macular edema in the left eye (). OCTA was performed in both eyes and showed decreased vascular density of the SCP of the left eye compared to pretreatment OCTA while a mild increase was noted in the vascular density of the SCP of the untreated right eye (Figures and ). The patient was then followed up without requiring further intravitreal injections and 4 months following the last intravitreal injection OCTA was repeated in both eyes and showed improvement of the vascular density of the SCP of the left eye with unchanged SCP in the right eye (Figures and ). CDVA was 20/60 in the right eye and 20/100 in the left. Clinical examination revealed retinal neovascularization in the right eye with clinically significant macular edema in both eyes. OCT showed increased center-involving macular edema in both eyes with recurrent neurosensory detachment in the left eye (). Three monthly intravitreal bevacizumab injections were then done for treatment of proliferative diabetic retinopathy in the right eye and the macular edema in both eyes. One month following the last intravitreal injection, CDVA was 20/40 in the right eye and 20/60 in the left, OCT showed decreased macular thickness in both eyes (), and OCTA revealed decreased vascular density of the SCP of both eyes (Figures and ). Changes in the deep capillary plexus closely followed those in the SCP at all stages. |
pmc-6500656-1 | A 74-year-old male with hypertension, dyslipidemia, diabetes mellitus, coronary artery disease, and end-stage renal disease was transferred to our institution due to the bilateral intermittent claudication 6 months before admission. He had been given 75 mg of clopidogrel and 200 mg of cilostazol per day. His right ankle-brachial index was unmeasurable, and echography was suggestive of right SFA-CTO. Although this lesion was classified as class D based on the Transatlantic Inter-Society Consensus Document (TASC) [], the patient refused surgical revascularization. Therefore, we chose endovascular therapy (EVT) and obtained a written informed consent from the patient. Since echography also indicated moderate stenosis of the bilateral iliac arteries, we initiated EVT in the right SFA-CTO using the contralateral approach. The first angiogram revealed the severely calcified SFA-CTO (; Video ). The antegrade approach with the stiff CTO wire resulted in the subintimal wiring. Therefore, we used the bidirectional approach with direct distal-SFA puncture. Finally, the retrograde-antegrade rendezvous technique led to wire externalization (; Video ). Regardless of the strong back-up force by wire externalization and child catheter support, no devices were able to pass the lesion by the antegrade and retrograde approaches and the thin balloon catheter was bent, Corsair microcatheter (ASAHI Intecc, Aichi, Japan) was fractured, Crosser system (C.R.Bard, NJ, USA) could not pass the lesion, and needle cracking technique [] from outside and inside of the vessel could not modify the lesion fully. Despite using all these techniques, a minimal balloon could not pass the lesion (). We consider abandonment and elective surgical conversion; however, bleeding from the retrograde puncture point and needle cracking techniques was uncontrollable. Therefore, we had to cross the lesion to perform balloon-assisted hemostasis.
Hence, we applied the ELA using the Turbo Elite 0.9 mm (Spectranetics, Co., USA). This device also could not pass the lesion; however, it modified the CTO entry-morphology (). After ELA ablation, the Caravel microcatheter (ASAHI Intecc) finally crossed the lesion using an antegrade approach with the BAlloon Deployment using FORcible Manner (BADFORM) technique [] (), which enabled change of the wire from conventional the 0.014-inch wire to 0.009-inch RotaWire floppy (Boston Scientific) and RotaLink Plus 1.5mm burr ablation (Boston Scientific) ().
Thereafter, we dilated the entire SFA lesion with conventional balloons and simultaneously achieved hemostasis of the distal-SFA puncture point. A bare nitinol stent was deployed due to severe dissection of the partial SFA. The final angiography revealed acceptable result without delay in blood-flow or bleeding complications (; Video Clips and ).
Thereafter we treated the bilateral iliac arteries using the bare nitinol stents. The right ABI of the patient improved from being unmeasurable to 0.79, and his intermittent claudication disappeared. His ABI and symptom has remained satisfactory eight months after current EVT. |
pmc-6500662-1 | The patient is a 47-year-old Caucasian female who presented to the Emergency Department of an academic tertiary-care hospital in the Midwestern United States with complaint of left-sided weakness of the upper and lower extremities and right gaze preference three weeks after a right pontomedullary infarct complicated by Posterior Reversible Encephalopathy Syndrome (PRES) [that initial infarct had been treated in a different state]. Imaging revealed an acute infarct in the posterior limb of the right internal capsule without hemorrhagic transformation and an acute punctate infarct in the right parietal subcortical white matter with corresponding diffusion restrictions, as well as remote evidence of subcortical chronic diffuse microhemorrhages (). The Psychiatry Consultation & Liaison service was consulted on hospital day 2 after the patient reported, “I want to strangle myself with my oxygen cord.”
On initial evaluation, the patient reported history of anxiety treated previously by her primary care physician (PCP). She reported she had been frustrated with her medical condition but really did not intend to harm herself. She reported fluctuating mood since her initial stroke and had “good days and bad days.” She denied prior history of inpatient or outpatient psychiatric care or prior suicide attempts. She was oriented to person and place, but not time, was able to state the days of the week forwards, but not backwards, and endorsed visual hallucinations during her hospitalization. This presentation was felt to be consistent with delirium, and she was started on quetiapine 25 mg.
Following a six-day medical admission, the patient was discharged to the acute inpatient rehabilitation unit housed within the hospital. Extensive diagnostic studies did not reveal an underlying etiology for the strokes, which were thought to be due to uncontrolled hypertension.
Psychiatry was reconsulted by the rehab physicians for management of problematic behaviors. The patient exhibited ego-dystonic behaviors for which she would later apologize including repeatedly climbing out of bed, shouting for nursing assistance without clear need for help, shoving her fist into her mouth to induce vomiting, and periodic, purposeless screaming. These behaviors were disruptive to staff and other patients on the unit. While initially conceptualized as residual hyperactive delirium, her behaviors persisted and continued testing for underlying causes of delirium including electrolyte derangement, occult infection, new or evolving cerebrovascular event, or excess medication burden which were unrevealing
After 60 days of acute rehab, she had reached maximal benefit of that intervention and continued exhibiting behaviors incompatible with nursing home disposition. The patient was then transferred to the university's geriatric psychiatry inpatient unit on an involuntary mental health commitment for behavioral management.
Ineffective medication trials prior to transfer included quetiapine (25 mg at bedtime and 25 mg several times daily as needed), mirtazapine (7.5 mg at bedtime), olanzapine (initial trial of 2.5 mg at bedtime and 2.5 mg several times daily as needed and a second trial of 15 mg and 2.5 mg several times daily as needed), buspirone (15 mg TID), divalproex (initial trial of 750 mg at bedtime and a second trial of 500 mg TID with lactulose and levocarnitine for hyperammonemia), melatonin (9 mg at bedtime), propranolol (40 mg QID), trazodone (150 mg at bedtime), gabapentin (200 mg several times daily as needed), dextromethorphan (20 mg BID, given as Robitussin), and clonazepam (0.5 mg AM and 1 mg PM).
Throughout this period, the patient remained intermittently apologetic for her behaviors. Orientation was typically attuned to person, sometimes place, and generally not to month or year. She consistently denied depressed mood, anxiety, visual hallucinations, auditory hallucinations, paranoia, suicidal ideation, or homicidal ideation. Thought process remained concrete and perseverative with limited spontaneous speech output and paucity of thought content. Language remained intact without evidence of aphasia. Recent and remote memory were difficult to assess formally due to behavioral disturbance, but she had difficulty remembering recent details of her hospital course and remote details of her life prior to moving to her current city. She required staff assistance for completion of toileting, dressing, and feeding. She had deficiencies in executing complex motor tasks, such as getting out of bed, and was frequently found diagonal in bed with a limb tossed over the side-rail. These deficiencies were in excess of the residual motor effects of her strokes and suggestive of alterations in visuospatial skills, executive function, and planning. Her aberrant vocalizations did not appear goal-oriented and were not ameliorated by staff presence. This presentation persisted and was thought to represent a new cognitive baseline meeting diagnostic criteria for major vascular neurocognitive disorder with behavioral disturbance.
Nonpharmacological strategies including music, sensory stimulation, one to one time with staff, and frequent repositioning were tried without improvement in her symptoms. Additional ineffective medication trials following transfer to inpatient psych included fluoxetine (60 mg per day), retrial of dextromethorphan with fluoxetine as an enzymatic inhibitor (again to 20 mg BID), retrial of quetiapine (up to 600 mg total per day), haloperidol (5 mg several times daily as needed IM), oxycodone (5 QID), lorazepam (up to 6 mg daily), carbamazepine (200 TID), and chlorpromazine (50 QID). Throughout these trials, the patient continued to exhibit frequent periods of severe psychomotor agitation requiring vest restraint and purposeless screaming alternating with periods of oversedation following medications. Other than providing intermittent sedation, no particular combination of medications proved effective in treating the target symptoms.
At this point, having exhausted all reasonable behavioral and pharmacologic options, the inpatient psychiatric team recommended ECT as a last intervention prior to pursuing a palliative approach. Medical Ethics was consulted and felt ECT to be consistent with her previously articulated beliefs and wishes.
The patient was formally evaluated by the ECT service and, given her incapacity to consent, a court order was obtained for the procedure. She underwent an acute course of bitemporal ECT using a MECTA Spectrum 5000Q machine. She received methohexital and succinylcholine as anesthetic and relaxant agent, respectively. A dose-titration method was used to determine stimulus intensity. She received treatments at 50% over seizure threshold with the following parameters: pulse width: 1 millisecond, frequency: 20 Hz, duration: 2 sec. Treatments were given three times per week. She was maintained on chlorpromazine (50 mg QID) and lorazepam (1 mg QID) during the treatments. Following the sixth ECT treatment, the patient rarely engaged in purposeless yelling, and remained quiet most of the day, experienced normalization of her sleep wake cycle, but still exhibited purposeless movements and psychomotor agitation requiring a vest restraint at night.
Following the third week of ECT treatments, she was consistently having low scores on the Pittsburgh Agitation Scale (PAS) and had minimal requirements for as needed medications for agitation []. While she still required a vest restraint overnight, her psychomotor agitation had improved dramatically. She resumed feeding herself with her right arm and tolerated pureed foods for the first time in six months. Following an acute course of 16 treatments, ECT was tapered to twice weekly and she started sertraline 25 mg in preparation for further decrease in ECT frequency. She remained stable and was successfully discharged to a nursing home with continuation of ECT as an outpatient. Following the expiration of the original court order for ECT, outpatient ECT was discontinued and the patient's family chose to not pursue a renewal of the order for continued treatment. She received 29 treatments in total. Nursing home staff reported that her behaviors remained in control after stopping ECT and she was thereafter able to return home with her parents. |
pmc-6500667-1 | A 60-year-old woman was admitted to the gynecology ward at our hospital to undergo anticancer chemotherapy for pulmonary metastatic uterine cervical cancer. On day 1, she received cisplatin plus irinotecan infusions. On day 2, fever >40°C, diarrhoea, haematuria, and right lower leg swelling developed. Blood culture was performed, and cefmetazole (CMZ) 1.0 g/day was begun. On day 4, the right lower leg swelling worsened. A blood test revealed increased serum inflammatory markers, and acute disseminated intravascular coagulation [] (DIC) and sequential organ assessment [] (SOFA) scores increased to 6 and 7, respectively. The patient was transferred to our department on day 5 at 00:30 hours. At the initial examination at our department (), the serum CRP and P-SEP level were 28.8mg/dl nad 1,635 mg/mL, respectively. The Glasgow Coma Scale was 14, blood pressure 88/52 mmHg, and heart rate 90 beats/minute. Although severe swelling was observed in the posterior aspect of the right lower leg, there was no warmth or redness anywhere on the right lower leg. A 9-cm2 patch of brown skin discoloration was noted on the anterior surface of the tibia. Because the right popliteal artery was compressed significantly by the severe swelling in the lower leg soleus muscle, and the image quality was poor, no apparent abscess formation could be confirmed by contrast-enhanced computed tomography (CT) at this time. The popliteal vein was completely occluded, and deep venous thrombosis developed. To prevent potential progression to compartment syndrome, a relaxing incision was made on the medial right lower leg, and no distinct signs of infection were observed in the subcutaneous tissues or muscles. The patient was transferred to the intensive care unit (ICU), and nafamostat mesylate 150 mg/day and recombinant thrombomodulin 19,000 U/day were begun, along with low-molecular-weight heparin 15,000 E/day for venous thrombosis. At this point, STSS was not suspected, and CMZ was continued. A blood test on the morning of day 5 revealed a further exacerbation of the inflammatory markers, a further increase in the acute DIC score, and no improvement in the SOFA score. The brown discoloration progressed rapidly to the entire right lower leg. At this point, STSS was suspected for the first time, and antibiotic therapy was switched to ceftriaxone 2 g/day plus clindamycin (CLDM) 1,200 mg/day, and γ-globulin 15 g/day was initiated. On the evening of day 5, blood culture (in the day 3 specimen) was positive for rapidly progressive group A streptococci. After day 6, while the skin discoloration expanded to above the right knee (), blood tests showed a trend towards improved. On day 14, the patient was transferred from the ICU to our general ward (). The mild swelling and feverishness of the right lower leg continued. Contrast-enhanced CT on day 32 revealed an encapsulated abscess in the right lower leg soleus muscle (). Debridement was performed with the patient under general anesthesia on day 34, close to the site of the relaxation incision. No organisms were isolated from the tissue culture of a specimen collected during debridement. After that, CRP remained at 0.4–0.6 mg/dL except during perioperative period, but P-SEP fluctuated between 350 and 380 pg/mL. We considered that local infections remained. And we continued to take oral minocycline (MINO) 200 mg/day. On day 50, CT revealed a residual abscess (). Therefore, we performed the second debridement on day 60. After that, P-SEP gradually decreased and CT confirmed the disappearance of the abscess and swelling on day 100 (). Oral MINO was discontinued after confirming that the P-SEP level had improved to 88 pg/mL (). Subsequently, the patient was returned to the gynecological ward without recurrent infection. |
pmc-6500834-1 | A 44-year-old female patient with ESRD on hemodialysis therapy three times per week for 9 years, was admitted to our hemodialysis center for a regular hemodialysis session program. She had arterial hypertension for 15 years. She had a permanent dual-lumen, cuffed, hemodialysis catheter (diameter 14, 5 Fr, cuff to tip 23 cm) which was inserted through the right jugular vein providing blood flow more than 350 mL/min. She had abdominal pain and dyspnea in dialysis session. Then a chest X-ray () and a thoracic CT () scan were performed and we found that her permanent catheter was inserted through the right jugular vein and had extended through the inferior vena cava and the distal tip of the catheter was ended in the middle hepatic vein. Meanwhile, we learned from the patient history that this catheter was functioning since three months and she was hemodynamically stable during this period. Because of the symptoms, the catheter was immediately removed. After removing the permanent catheter, the symptoms were resolved. Before replacing a new permanent catheter, a venography for upper extremities and superior vena cava was performed by interventional radiology and no flow of contrast agent was observed in superior vena cava vein, suggesting an obstruction in vena cava superior vein and right and left juguler vein’s blood flows were through azygos and hemiazygos veins respectively. So a new functioning permanent, dual-lumen, cuffed, hemodialysis catheter (diameter 14, 5 Fr, cuff to tip 19 cm) was inserted in the right femoral vein. |
pmc-6500850-1 | We report a case of a thirty year old woman, married, mother of three, and resident of a village which is located 560 KM from Karachi (the city where this institution is located). The lady gave birth to a child 12 days prior to her admission in this hospital. The neonate was alive, born preterm, through spontaneous vaginal mode. The child was born at home with assistance of local women; reportedly there was no unusual blood loss at time of child birth. The woman did not had any antenatal visits therefore blood pressure recording and urinary analysis not available. She became anuric after child birth, thus referred to this hospital which is a tertiary renal care unit.
When reached for further details regarding her illness it was found that she had non specific poly arthralgias and undocumented intermittent low grade fever over last approximately two months. There was no history of decline in weight or loss of appetite, patient had no previous history of Tuberculosis or of contact with tuberculosis patients. She had a history of taking analgesics for non specific joint and body aches. There was no history of any other medical problem or surgical procedure in past.
On arrival here her clinical examination revealed anemia, no peripheral edema, multiple palpable non tender right sided cervical lymph nodes, normal nails and skin. Her blood pressure was 130/70, temperature 1000F, pulse 100/minute and respiratory rate 22/minute. Cardiovascular, respiratory, abdominal and neurological examination was normal.
Laboratory hematological parameters were as follows; hemoglobin was 7.0 g/dl (reference range 12.0-15.5), white blood cell count was 18.0×109/L (reference range, 3.5–10.5×109/L) and consisted of 77% neutrophils, 8% monocytes, 13% lymphocytes, 1% basophils, and 1% eosinophils. Platelets were 738,000 (reference range 150,000-400,000 ×109/L), ESR was 65 mm during first hour.
Routine chemistry included urea of 225 mg% (reference range 10-50 mg%), creatinine was 12.8 mg% (reference range 0.5-1 mg%), serum sodium was 145 mEq/l (136-149), potassium 5.6 meq/L (3.5-5.2), chloride 100 mEq/L (98-107), bicarbonate 22 mEq/L (25-29). LDH was 612 (reference range 91-180 U/L), liver function tests, serum calcium and total proteins were within normal limits. Serology revealed C3 of 0.7 (reference range 0.79-1.52 g/L), C4 of 0.4 (reference range 0.16- 0.38 g/L), ANA and Anti DNA were negative. Viral serology for HBV, HCV, EBV and HIV were negative. Urinalysis on dipstick revealed protein 3+ and rest normal. Microbiology for blood and urine cultures was negative. Chest radiograph was negative for any masses or lymphadenopathy. Ultrasonography of abdomen showed normal size kidneys and normal rest of examination.
Her renal biopsy was performed which revealed findings consistent with HUS, and cervical lymph node biopsy revealed findings of KD. ( and )Informed consent was taken before all procedures, that is vascath placements and lymph node or renal biopsy. These consent forms include one segment mentioning that this information can be shared in scientific publications without mentioning patient’s identification.
The patient was treated with renal replacement in form of hemodialysis. While plasma exchanges done for 10 consecutive days, after getting renal biopsy report. Oral prednisolone @ 1mg/kg/day was started after receiving lymph node biopsy report. Patient was discharged because she was desperate to go home to see her children, as her renal functions did not improved till time of discharge from hospital she was advised to come back in three days but she never returned. When contacts was made on cell number provided at time of hospitalization, patient’s brother informed that she died two days after reaching home, it was sudden death and they could not consult even nearby doctor. |
pmc-6500988-1 | A 61-year-old female former smoker with a smoking index of 17.5 pack-years and underlying chronic obstructive pulmonary disease, sleep apnea syndrome, and hyperlipidemia, was diagnosed with stage IVA of cT2bN1M1a (PLE) lung adenocarcinoma of the left upper lung lobe without EGFR mutations or ALK fusion (Fig a,d). The PD-L1 tumor proportion score was > 90%.
She was treated with three courses of systemic chemotherapy consisting of cisplatin and pemetrexed as a first-line treatment, which resulted in the growth of the tumor. Three months later, pembrolizumab (200 mg/body every 3 weeks) was started as a second-line treatment. She developed destructive thyroiditis before the third course of pembrolizumab, with her free T3 level increasing to 7.2 pg./mL and her thyroid stimulating hormone (TSH) level decreasing to 0.029 μIU/mL. At this time, she exhibited no objective symptoms; therefore pembrolizumab was continued. Before administration of the fifth course, thyroid hormone treatment was initiated because her thyroid function had begun to decline and her TSH level had increased to 46.6 μIU/mL (Fig ).
Subsequently, she experienced vomiting, general malaise, and thirst from day 8 of the eighth course. She was urgently hospitalized two days later. At admission, her blood glucose level was markedly high (572 mg/dL), her hemoglobin A1c (HbA1c) level was 8.4%, her blood and urinary C-peptide levels were remarkably low, and a urinary ketone body test was positive (Table ). She was diagnosed with fulminant type 1 diabetes mellitus (T1DM) with ketoacidosis. After two days of fluid and electrolyte compensation and insulin therapy, her blood glucose level was well controlled and her ketoacidosis improved. Thereafter, insulin treatment for T1DM was continued (Fig ). An anti-glutamic acid decarboxylase (GAD) antibody test, which was performed at a later time point, was negative. She did not develop any other irAEs.
Interestingly, at the onset of T1DM, the mass in the left upper lobe decreased (Fig b,e). The continued administration of pembrolizumab, even after the onset of T1DM, further reduced the size of the primary lesion (Fig c,f). However, after 21 courses of pembrolizumab, the primary lesion alone showed slight enlargement (within the range of stable disease). The administration of pembrolizumab was interrupted and radiotherapy was performed for local control of the primary tumor. |
pmc-6501021-1 | We present a case of 74-year-old man with a 22 mm subpleural pulmonary lesion in the apical portion of the right lung, detected by a CT scan performed during a pulmonary consult for his chronic obstructive pulmonary disease (COPD). Bubbles of emphysema surrounded the lesion, which is non-specific for a diagnosis of CCTL (Fig ).
To determine the histological nature, we performed a CT-guided core biopsy of the lesion. Microscopic examination revealed a clear cell non-small cell lung carcinoma with focal and weak nuclear positivity to TTF-1 and negativity to p63 and synaptophysin reactivity. A staging total body contrast-enhanced CT scan revealed a 28 mm lesion on the right apical pulmonary lobe but no distal cancer spread. Additional preoperative positron emission tomography (PET)-CT with 18F-fluorodeoxyglucose (18F-FDG) confirmed the presence of a highly metabolic pulmonary node in the apical portion of the right lung (maximum standardized uptake value 6.3). Thus, the patient underwent thoracic surgery with the right lobectomy technique and associated D2 ilo-mediastinal lymphadenectomy.
On pathological analysis, macroscopically, the lung lobe measured 13 x 11.5 x 3.5 cm. On the subpleural level there was a grayish nodule with infiltrative margins of 2.5 cm, while the remaining lung tissue was macroscopically normal. The histological exam confirmed moderately differentiated (G2) clear cell adenocarcinoma of the lung with an acinar growth pattern that had infiltrated the lung tissue without visceral pleural involvement. The neoplastic cells had a large and clear vacuolated cytoplasm. The nucleus was round or slightly indented, with finely dispersed chromatin and inconspicuous nucleoli, and several mitotic figures were observed.
Immunohistological evaluation was positive for CD10, vimentin, pan-CK, MNF116, and CK7 but negative for TTF-1 (Fig ). All 10 of the removed lymph nodes were negative for metastasis. According to current tumor node metastasis stage grouping, the disease was classified as pT1c; pN0 (0/10) cMo (stage IA3). A possible renal origin of the cancer could not be excluded. We performed postoperative radiological evaluation with a total body CT scan that was negative for residual mass, metastatic dissemination, and primary clear cell renal carcinoma (Fig ). After consultation and considering the absence of any residual illness or metastatic spread, the disease management team decided not to administer adjuvant chemotherapy but to continue specific postoperative oncologic follow-up. After four years of follow-up the patient is in good clinical condition with no evidence of recurrent or metastatic disease (Fig ). Written informed consent was obtained from the patient for publication of this case report and any accompanying images. |
pmc-6501053-1 | A 69-year-old man presented to our hospital with lung nodules at the right upper and right lower lobes, which were detected at a different institution during an examination for intermittent hemoptysis. The patient's past medical history was significant for hypertension, with a smoking history of 50 pack-years. Physical examination and routine laboratory tests revealed no significant findings. A chest computed tomography (CT) scan revealed a 2.1 × 1.7 cm sized mass in the posterior segment of the right upper lobe (RUL), along with a 3 × 2.3 cm sized mass in the superior segment of the right lower lobe (RLL)(Fig a). The nodule in the RUL was suspected to be primary lung cancer, while the nodule in the RLL was suspected to be a benign neoplasm or double primary lung cancer. Therefore, we performed a staging workup for suspected lung cancer. Positron emission tomography showed increased uptake only in the RUL and RLL (Fig b). Bronchoscopy showed no endobronchial involvement. As the pulmonary function test indicated no contraindication, we recommended surgery because of the possibility of malignancy in each nodule. Thoracoscopic wedge resection was performed with a frozen section for each nodule. The intraoperative frozen section revealed adenocarcinoma with poor differentiation in the RUL and non-small cell lung cancer with very poor differentiation in the RLL. CT findings showed a RUL lesion with spiculated margins and a RLL lesion with well-defined margins. We performed an additional upper lobectomy with mediastinal lymph node dissection after the thoracotomy considering the CT findings and an insufficient wedge resection margin of the RUL. The patient was discharged from the hospital without any complications on postoperative day eight.
The results of the biopsy revealed that despite poor differentiation of the tumor cells, the RUL mass was an adenocarcinoma positive for CK7 and TTF-1 (Fig a,b). The RLL mass was a tumor consisting mostly of cells that morphologically looked like epithelial cells, many of which showed apparent dysplasia and cell division (Fig c,d). This tumor was negative for CK, CD34, and TTF-1, but positive for vimentin and actin (Fig ). Based on these pathological findings, the final diagnosis was an adenocarcinoma in the RUL and a malignant glomus tumor in the RLL. As lymph node metastasis had not developed, no adjuvant chemotherapy or radiation therapy was administered. The patient has remained healthy and without recurrence for three years following the procedure and is currently in follow-up at an outpatient setting. |
pmc-6501058-1 | A 19-year-old male patient, with body mass index (BMI) of 8.45 kg/m [] and previous diagnosis of cerebral palsy, was admitted due to upper gastrointestinal bleeding Blatchford score of 10. Upon initial assessment, the patient required a blood transfusion due to hemoglobin level of 5.48 g/dl. The upper gastrointestinal endoscopy reported an esophageal ulcer Forrest IIC and esophagitis. Given the symptoms associated with chronic malnutrition and severe deconditioning, a gastrostomy was recommended. Initially an endoscopic gastrostomy was decided as the ideal approach, which was unsuccessful due to suboptimal translumination. Despite considering a new attempt to perform endoscopic gastrostomy at a later date, the patient´s nutritional and metabolic condition could worsen in case it failed a second time. Thus, an open gastrostomy was considered by the gastroenterology department to ensure an early start of the enteral nutritional route. The institutional anesthesiologist considered the patient’s high risk would be reduced once he was in adequate nutritional and metabolic so the surgery was performed without any initial complications. An upper gastrointestinal endoscopy on the third postoperative day revealed adequate positioning of the gastrostomy and enteral nutrition was initiated and well tolerated.
Ten days after surgery, patient in-hospital presented diffuse abdominal pain and multiple diarrheic episodes, of insidious origin, referring it began two days after surgical procedure and gradually increased its intensity. Laboratory results were within normal limits, and the abdominal computed tomography (CT) scan revealed extensive pneumatosis from esophagus, stomach, small intestine and partial colon. Additionally, moderate pneumoperitoneum and gas in the venous portal system were also reported (, ). The CT scan showed no evidence of an intra-abdominal collection or abscess that could otherwise explain the findings, as there was also no clinical or laboratory signs of systemic inflammatory response syndrome or infection. Medical management was initiated with intravenous fluids and nasogastric tube, while suspending the enteral nutrition. Patient showed improved outcome regarding symptomatology 24 h later. One month after the surgery, the patient was discharged in good conditions, with nutritional supplement via gastrostomy and integral rehabilitation. |
pmc-6501124-1 | A 72-year-old man with a long history of smoking was referred to the emergency department on suspicion of cauda equina syndrome. Mild spinal stenosis of the L4/L5 and presacral level had been found on MRI previously during a workup for moderate claudication. Other preexistent medical conditions included hypertension, diabetes, and obesity. On the previous day, his back pain had acutely worsened; difficulty in urinating and fecal incontinence had appeared. The patient had not been able to walk properly. On examination, acute urinary retention was found, as well as diminished anal sphincter function and saddle anesthesia. There was no weakness or sensory loss in either legs. The pain was localized in the lower back. The inflammation markers were markedly elevated, and the patient was feverish. Large ulcers were found in the scrotum and in the gluteal area. No vascular examination was performed. MRI of the lumbar spine was requested, and a severe spinal cord stenosis of the L4-L5 and L5-S1 levels was found. An urgent decompression procedure was performed on the same day. L5 hemilaminectomy, L4 laminotomy, and partial S1 laminotomy were performed. The findings were consistent with a moderate spinal cord stenosis. Septic shock developed during surgery, and the patient was admitted to the ICU after completion of decompression. Extensive necrotic tissue debridement was undertaken. Bacteriological cultures of samples showed polymicrobial flora, consistent with Fournier's gangrene. The patient's clinical condition did not improve, and later in ICU, both legs were found to be cold to the touch; skin appeared “marble” white. Femoral pulses were not palpable, and the skin of the lower extremity was cyanotic. A vascular surgeon was consulted, and CT angiography of the aorta and lower limbs was requested. The findings were consistent with acute on chronic aortoiliac occlusion ().
An urgent embolectomy through bilateral groin incision was performed. Because of extensive disease of the iliac arteries, the embolectomy was not successful, and an aortobifemoral bypass with Y-prosthesis was performed. Circulation was successfully restored to the legs. Several debridement procedures and skin graft were later needed to repair the extended skin and subcutaneous necrosis in the gluteal and scrotal areas. Postoperatively, the right groin surgical wound developed superficial seroma, which was successfully treated surgically with debridement. Closure was achieved through a sartorius muscle flap. Later, the recovery was complicated by acute coronary syndrome, which required a coronary artery bypass. Eventually, the patient's conditions improved, and he was transferred to a secondary center, where his recovery continued uneventfully. After a long hospitalization, the patient underwent physical rehabilitation. The gluteal and scrotal areas needed several interventions and were eventually reconstructed with a muscular flap. The patient is currently able to walk, does not need urinary catheterization, and lives at home. |
pmc-6501135-1 | A 20-year-old female was initially diagnosed at the age of 13 (2010) with pan-UC. In the following years, she was treated with mesalamine, corticosteroids, cyclosporine, and azathioprine; however, no satisfactory clinical or endoscopical response was observed. Corticosteroid-dependent disease despite immunosuppressive therapy led to the initiation of infliximab in 2011. The response was positive, but the treatment was terminated after the 3rd dose due to anaphylaxis. Thereafter adalimumab was introduced; however, the patient did not respond to the therapy. From the beginning (2010), extraintestinal manifestations of IBD, especially from the joints and skin, occurred; therefore, the patient was also under rheumatologist supervision with the diagnosis of reactive arthritis and leukocytoclastic vasculitis. In the same time period, due to persistent isolated (although detectable) IgA deficiency, partial IgA deficiency was also diagnosed.
In 2012, the patient was referred to a surgery unit with the intention of proctocolectomy with ileal pouch-anal anastomosis (IPAA). However, due to uncertain nature of the disease, a total abdominal colectomy (TAC) and ileal-rectal anastomosis (IRA) were performed.
The postcolectomy histopathology revealed fulminant active chronic inflammatory bowel disease, fully in keeping with active chronic ulcerative colitis involving the whole colon; spontaneously visible deep ulcerations might eventually suggest indeterminate colitis or CD. Although the terminal ileum appeared normal, the j-pouch was not formed. Repeated serology was again negative for both perinuclear antineutrophil cytoplasmic (p-ANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA).
In 2013, the patient was hospitalised in the Rheumatology Department where Sjögren's syndrome was recognised with a typical clinical (xerostomia, xerophthalmia, lymphadenopathia, and inflammation of the parotid glands), serological (specific antinuclear antibodies), and histological (labial glands biopsy) features. Initially, due to severe joint complaints, methotrexate was introduced to the treatment. Because of abdominal side effects, methotrexate was withdrawn and chloroquine added.
In February 2017, the patient was admitted to our department due to severe anemia, increased fatigue, and anxiety. She also complained of abdominal and anal pain; her bowel frequency was 20 times during the day and 5-6 times at night, passing urgent loose stools. An endoscopy showed diffuse edematous inflamed mucosa within the ileum, ileorectal anastomosis, and bleeding inflammatory changes in the rectal stump.
Pathology of the ileal biopsy revealed mixed, acute, and chronic inflammatory infiltration of moderate grade. Her symptoms poorly responded to an empirical course of ciprofloxacin with metronidazole and topical hydrocortisone.
Two months later a follow-up endoscopy showed progression of inflammatory changes—diffuse edematous inflamed mucosa with small superficial aphthous-like lesions and superficial bleeding visible within the whole examined ileum []. The pathology specimen showed typical features of UC []. In MR enterography no CD-like or other lesions were found. In the meantime, again negative results of viral pathogens, celiac serology, and antibodies to enterocytes and stool cultures were obtained. UC-related pan-enteritis was suspected and the decision of systemic steroid dose escalation up to 40 mg of methylprednisolone iv was made. However, no satisfactory symptom resolution was achieved; therefore, GI cut-off followed by parenteral nutrition (TPN) was initiated and she was discharged with an oral methylprednisolone taper and mesalamine.
After three months of home TPN, the patient was admitted to hospital due to abdominal aggravation of symptoms followed by more than 20 bloody stools per day. Surprisingly, in the pelvic MR imaging, the presence of rectovaginal fistula was visualised. An endoscopy revealed active mucosal inflammation within the ileum, ileorectal anastomosis, and also rectal stump []. In addition, the patient had symptoms of active arthritis. Based on the history of previous azathioprine, cyclosporine, methotrexate, and infliximab intolerance, MMF in a daily dose of 1500mg was initiated. A follow-up visit revealed no clinical nor endoscopic improvement. What is of importance here, apart from MMF, was that the patient was still treated with low doses of oral steroids, mesalamine, and chloroquine. In the meantime, the patient was also advised to undergo surgical treatment including end-ileostomy, but due to consent refusal, the surgery was not performed. Therefore, VDZ in a standard dose of 300mg intravenously was introduced to the therapy. After the 3rd dose of induction treatment, a significant reduction in the number of stools (<10 per day) and less rectal bleeding was observed, but at this time no endoscopic improvement was noticeable. However, the next endoscopy scheduled ten weeks later revealed significant endoscopic improvement [Figures and ]. Moreover, the patient reported significant fistula improvement. Currently, the patient is in steroid-free remission of enteritis and arthritis on MMF and continuing maintenance therapy with VDZ. |
pmc-6501167-1 | An 81-year-old male patient was referred to our department with dysphonia. There was no history of smoking. A status past multiple myeloma was known in his medical history that was in complete remission at the time of presentation. The patient denied dyspnea, dysphagia, pharyngalgia, and fever. Laryngoscopy revealed a diminished mobility of the right vocal cord and a thickening of the right vestibular fold so that a microlaryngoscopy with tissue sampling was performed. The histological examination of specimens obtained from this region revealed fibrosis. Computed tomography (CT) scans of the neck and the thorax were without any pathologic findings. The patient was discharged to outpatient care.
Three months later, the patient was admitted with progressive dyspnea along with inspiratory stridor. The clinical examination revealed now a complete paralysis of the right vocal cord and a remaining glottic cleft of only 1 mm due to a supraglottic protrusion of the right vestibular fold. The CT scan () showed now a tumor of the right vocal cord extending to the right piriform sinus.
After tumor debulking in order to expand and secure the airway, the excised material that consisted of several red brown elastic tissue fragments measuring together 24 × 12 × 10 mm was sent for pathological examination. Histologically, one could see tight lymphoid infiltrates. The cells had large nuclei and were irregularly shaped, and the proliferation was strongly enhanced in the staining for Ki67 (50%). The immunohistochemical analyses showed a negative result for CD20 and CD3, and a positive staining for CD138. BCL2 and CD10 were coexpressed (). The clonal light chain restriction for lambda chains substantiated the diagnosis of a multiple myeloma. These results were consistent with laryngeal involvement from the patient's previously diagnosed multiple myeloma.
The patient was referred to the Department of Hematology and a systemic therapy with the proteasome inhibitor Bortezomib was discussed. Ultimately, instead of that, a local radiation therapy with 60 Gy was performed. In a control laryngoscopy with tissue sample taken after the radiotherapy, the myeloma could not be verified anymore. The patient is in continuous otorhinolaryngological and oncologic follow-up. To date, almost two years later, no recurrence of the myeloma has occurred so far. |
pmc-6501194-1 | A 92-year-old man with osteoarthritis and a remote history of right total hip replacement and bilateral total knee replacements presented with a two-day history of severe right hip pain accompanied by nausea, chills, and fatigue. He was unable to bear weight due to pain, and range of motion in his right hip was severely limited. He denied recent trauma or pain in other joints but had undergone routine dental cleaning one week prior to presentation. He had received 2 gm of amoxicillin immediately prior to his dental procedure. He presented afebrile, mildly hypotensive, and was noted to have exquisite tenderness with passive movement of the right leg and reduced range of motion secondary to pain. He had full range of motion and strength distally. He had a leukocytosis of 15,600 WBC per milliliter. Aspiration of right hip joint revealed cloudy fluid with WBC 68,000 cells per milliliter. The patient was resuscitated with IV fluids and started on vancomycin and piperacillin-tazobactam. On the third hospital day, he underwent prosthetic joint drainage and washout with retention of liners. Joint aspirate culture grew Gram-positive cocci in chains, which we subsequently identified by matrix-assisted desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) as S. salivarius. We narrowed antibiotic therapy to ceftriaxone to complete six total weeks of intravenous therapy, after which he was treated with amoxicillin for additional six weeks. At this point, the patient discontinued his oral antibiotics rather than complete a full three months of oral therapy or remain on long-term suppression.
Five months after completion of the above therapy, the patient presented to the ED with hip and back pain following a mechanical fall at home. He was found to have a fracture of L4 and was admitted. On hospital day 5, he was found to have an occult superior dislocation of the R femoral head on CT and an ESR of 71 and CRP of 12.3. He was taken to the OR for single-stage full revision of his prosthesis the following day. One of the three intraoperative cultures had light growth of coagulase-negative staph and S. salivarius, though no WBCs were seen and gram stain was negative. He was treated with 6 weeks of vancomycin and remains on lifelong antibiotic suppression. |
pmc-6501217-1 | An 80-year-old, white Caucasian man was presented to our hospital emergency department with one-month history of jaundice, pruritus, acholic feces, dark urine, unintentional weight loss, and worsening pain in the lumbar region. On the date of admission the urine was light yellow and the patient reported that feces were of normal color and consistence. He denied alcohol or illegal drug use and had no travel history within the last 10 years. He reported jaundice and pruritus progressing for one month prior to admission. He denied having pain, nausea, vomiting, or elevated temperature during the whole month. Pain in the lumbar region was progressing during the last 2 years, due to PCa metastasis. Patient had metastatic PCa and underwent palliative hormonal therapy in ambulatory settings; he also had moderate aortic stenosis found by echocardiography and angina pectoris of class II according to the classification system by Canadian Cardiovascular Society. In year 2016, metastatic process involving the lumbar spinal and thoracic region was diagnosed using skeletal scintigraphy. Starting from year 2016 he received androgen deprivation therapy in outpatient settings and testosterone level was controlled in conjugation with PSA. Testosterone remained at castrate level.
During physical examination, yellow skin, scratch marks on the back and thorax due to pruritus, and aortic murmur were revealed.
Blood tests indicated that the patient had cholestasis, elevated alanine aminotransferase, elevated aspartate transaminase, elevated gamma-glutamyl transferase, and elevated bilirubin (). Infectious disease such as hepatitis C and hepatitis B was excluded using testing for antibodies. Autoimmune causes were also excluded; anti-mitochondrial antibody, anti-glycoprotein antibody-210, and anti-sp100 antibodies, IgA and IgM, were all negative. Alpha-fetoprotein was also negative. Alkaline phosphatase (ALP) was significantly elevated; thus isoenzyme of bone origin ALP2 was determined to differentiate the source of elevated ALP (). Ultrasound examination of abdomen was performed, with no evidence of extrahepatic bile duct dilatation or cirrhosis. Magnetic resonance cholangiopancreatography showed no cholestasis, but 1.5 cm diameter cyst was found in hepatic parenchyma. The patient received supportive and symptomatic therapy.
Rapid deterioration of general health status occurred during hospitalization, with exitus letalis while in the hospital. |
pmc-6501223-1 | A 46-year-old white female with a 15 pack-year smoking history initially presented 3 years ago with intense pain in the left side of the mouth that radiated to her left ear for 2 months. She was found to have a 2 cm exophytic lesion on the left lateral border of her tongue that was diffusely keratotic and extremely tender on examination. Fiberoptic laryngoscopy revealed normal findings in the nasopharynx, oropharynx, and hypopharynx. Histological biopsy of the tongue lesion confirmed well-differentiated squamous cell carcinoma of the left lateral border of the tongue. Radiographical findings on positron emission tomography (PET) scan showed hyperactivity along the left lateral aspect of the tongue and a mildly hypermetabolic left level IIa cervical lymph node with no evidence of distant metastases ().
The patient was treated with a left hemiglossectomy and bilateral neck dissection. Pathologic evaluation revealed a 2.4 cm moderately differentiated, infiltrating squamous cell carcinoma of the left lateral tongue lesion invading into the skeletal muscle with a 0.5 cm maximal thickness. There was perineural invasion, but no lymphovascular invasion, and all margins were free of cancer. A total of 3 out of 22 lymph nodes were positive for carcinoma: 0 out of 10 in right neck level II-III, 2 out of 5 left level I with no extracapsular extension (ECE), 0 out of 1 left level II, and 1 out of 6 left level III with no ECE.
She was staged as pT2 pN2b M0 (stage IVA, AJCC 7th edition 2010) squamous cell carcinoma of the left lateral tongue. She received adjuvant treatment with concurrent afatinib and radiotherapy to a total dose of 6000 cGy in 30 fractions over 6 weeks to the oral cavity and bilateral necks, which was completed in 3 months after diagnosis.
Interval radiographical imaging did not show any evidence of disease recurrence or distant metastases until 2018. At that time, the patient had developed increasing left arm pain, left ear pain, and left throat pain. She also reported intermittent chest pressure, exertional dyspnea, and intermittent dizziness with positional changes.
In early 2018, a PET scan () and magnetic resonance imaging (MRI) of the chest () showed a new 3.4 cm left apical pleural mass encasing the left subclavian artery and abutting the left subclavian vein, both of which were patent. A computed tomography-guided fine-needle aspiration (CT-FNA) of the apical lung mass revealed squamous cell carcinoma.
Shortly after, the patient began systemic therapy with cisplatin and etoposide and radiation therapy to the left apical lung lesion. Following the 20th fraction of radiation therapy, a repeat computed tomography (CT) scan of the chest revealed a new 1.2 cm lesion in the inferior interventricular septum of the heart. A cardiac ultrasound was performed and demonstrated a mass in the left ventricle. The patient went on to complete radiation therapy to a total of 6000 cGy in 30 fractions. Further diagnostic imaging with a cardiac MRI was performed, which revealed a mass infiltrating the left ventricle, inferior myocardium, epicardial fat, and pericardium with associated mobile thrombus formation (). A PET/CT scan demonstrated hypermetabolic lesions in the left neck, right thigh muscles, lung parenchyma, heart, anterior mediastinum, left scapula, and posterior right rib (). Transthoracic echocardiogram (TTE) showed a 1.6 × 1.4 cm mobile mass in the left ventricle cavity that appeared to be attached to the base of the papillary muscle and a normal left ventricular ejection fraction of 60%. An electrocardiogram (ECG) revealed normal sinus rhythm with T-wave inversion in the inferior leads and V3–V6.
The patient initiated anticoagulation and systemic therapy with nivolumab. |
pmc-6501225-1 | Our patient is a 64-year-old African American male with a past medical history significant for coronary artery disease status post percutaneous coronary intervention in the setting of a non-ST elevation myocardial infarction, hypertension, hyperlipidemia, diabetes mellitus type 2, chronic kidney disease stage III, and prior bariatric surgery. He presented to the emergency department with complaints of fatigue and progressive drainage from a left foot wound with associated pain. The patient was hypotensive (blood pressure 89/53 mmHg) and bradycardic (43 beats/minute) with complete heart block noted on telemetry monitoring and confirmed on 12-lead electrocardiogram. Initial laboratory tests were significant for leukocytosis (white blood cell count 32.1 K/mm3), anemia (hemoglobin 9.5 g/dl), and elevated BUN (51 mg/dl) and creatinine (3.6 mg/dl) from baseline. A temporary transvenous pacemaker was placed emergently in the cardiac catheterization laboratory. The patient was subsequently hospitalized for the management of septic shock, wet gangrene of the left second toe, and complete heart block. Empiric antibiotic therapy was initiated with vancomycin and piperacillin/tazobactam, and he underwent urgent toe amputation followed by left ankle disarticulation. Postoperatively, the patient developed respiratory failure requiring intubation. Initial blood cultures grew MRSA. Given persistent hemodynamic instability despite presumed infectious source control, echocardiography was performed to rule out infective endocarditis. Transthoracic echocardiogram (TTE) on hospital day 1 and TEE on day 3 were, however, noncontributory (). Bacteremia was persistent through the second week of hospitalization on multiple sets of blood cultures, and antibiotic regimen was changed to ceftaroline. Due to the persistent bacteremia, a whole-body 18-florodeoxyglucose positron emission tomography/computed tomography (18F-FDGPET/CT) scan was then obtained on hospital day 8 which revealed multiple PET-avid lung nodules and cavitary lesions concerning for septic pulmonary emboli (SPE). TEE was then repeated on hospital day 9 revealing a highly mobile echodensity in the right ventricular outflow tract (RVOT) measuring 3.4 cm by 1.6 cm () without valve leaflet or chordae involvement. The patient was evaluated for surgical vegetectomy; however, his surgical risk was deemed prohibitive in the acute setting, and thus conservative management was pursued with antibiotic therapy alone. Infection control was not successfully achieved. From a Heart Team approach, the decision was made to attempt an AngioVac evacuation of the RV mass on hospital day 12.
Venous access was obtained at both femoral venous sites with 6-French sheaths, and a right internal jugular access was obtained for the replacement of a temporary pacemaker. The left 6-French sheath was changed out with a 17-French cannula after serial dilatation while the right sheath was replaced with a number 26 DrySeal Sheath. Using a Swan-Ganz catheter, a Swan wire was positioned into the right pulmonary artery (PA). Using an MPA catheter, a Lunderquist wire was positioned in the right PA. The AngioVac return cannula was then attached with a wet-to-wet seal to the perfusion pump. The return cannula was loaded over the Lunderquist wire after removing air from the cannula. Under TEE guidance, the return cannula was advanced into the right atrium. When the return cannula could not be advanced further into the RV outflow tract, it was pulled back and the Lunderquist wire was repositioned into the left PA using the MPA catheter. It was then possible to advance the aspiration catheter back and forth, and this resulted in the return of a large amount of material visually consistent with clots. Activated clotting time was maintained above 300 seconds throughout the procedure with heparin. Postprocedure TEE showed up to 90% resolution of the mass (). Aspirated blood sampled from the PA was positive for MRSA. Antibiotic therapy was continued, and subsequent blood cultures were sterile. Resolution of complete heart block was verified on continued telemetry monitoring, and the temporary pacemaker was removed. The patient was eventually discharged in stable condition on hospital day 27. |
pmc-6501228-1 | An 82-year-old man sustained an acetabular fracture on the left side involving the anterior and posterior columns after falling from a bicycle (Figures and ). He was in shock on arrival with impaired vital signs and systolic blood pressure. Contrast computed tomography scanning showed bleeding from the internal iliac artery. Hence, external fixation and transcatheter arterial embolization were performed in the emergency room on the same day. He then underwent internal fixation 11 days after the injury when his condition was stable. Surgical repair of the fracture was performed in two phases.
First, we used the ilioinguinal approach to access the anterior column and carried out an open reduction and internal fixation (ORIF) using a reconstruction plate and screws. The displaced large fragment of the quadrilateral surface and arcuate line of the ilium were observed well. Although reduction was achieved, there were significant cancellous bone defects causing impaction of the acetabulum. Hence, Affinos®, in both granular and block forms, was placed in the bone defect without impaction so as to not break the micro structure before fixation with the plate. We then used the Kocher-Langenbeck approach to access the posterior column, wherein the overall fixation was neutralized by the reconstruction plate contoured to accommodate the shape of the posterior column (). Partial weight bearing started 6 weeks after surgery, and the patient could walk 100 m using a cane 5 months postoperatively. At the time of the final follow-up, 18 months postoperatively, the patient was able to perform stair climbing without pain and the radiograph showed stable fixation without osteoarthritic change (). The patient's modified Harris hip score was 85 at the final follow-up. We observed absorption and bone fusion around the artificial bone (). |
pmc-6501230-1 | A 68-year-old man was initially diagnosed with right primary choroidal melanoma by histopathology and immunohistochemistry (IHC). He was treated with I-125 plaque brachytherapy in 2013. In April 2016, an abdominal ultrasonography (US) revealed multiple scattered hypodense lesions throughout the liver; the largest lesion was within segment 7 measuring 6.6 × 5.1 cm (M1b). A US-guided liver biopsy confirmed a recurrence, with a lactic acid dehydrogenase (LDH) level of 220 U/L (110-270 U/L) and alkaline phosphatase (ALP) of 22 (7-52 U/L). In April 2016, the patient started a combination of ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) administered every 3 weeks. After three cycles of treatment, imaging revealed the same number of hypodense lesions; the largest lesion measured 5.5 × 3.4 cm (). In July 2016, treatment was stopped due to severe autoimmune colitis as a side effect of the immunotherapy. Later that year, in September 2016, the patient continued nivolumab alone (240 mg every 2 weeks), which was also discontinued in February 2017 due to intolerance. Since then, the patient had received transarterial chemoembolization (TACE) for the hepatic lesions. In June 2017, the patient developed progressive disease, with an LDH of 317 U/L and ALP of 426 U/L. The patient was enrolled to hospice care and the patient expired within a month. |
pmc-6501230-2 | A 69-year-old man was referred to an ocular oncologist in 2014 due to visual changes in his left eye. He underwent enucleation in 2014 and histopathology showed T3aN0M0 choroidal melanoma. He underwent systemic staging and did not have metastatic disease at the time. Later in April 2016, surveillance imaging showed multiple pulmonary nodules (M1a), which were diagnosed as metastatic disease by right lung lower lobe wedge resection confirmed by IHC (HMB-45 and MART-1), with an LDH of 191 U/L and ALP of 84 U/L. In July 2016, the patient started nivolumab (1 mg/kg) and ipilimumab (3 mg/kg) administered every 3 weeks. Upon completion of four cycles, the treatment was stopped due to autoimmune colitis as a side effect of immunotherapy. Imaging surveillance in September 2016 showed progressive disease, with an LDH of 231 U/L and ALP of 89 U/L, and the patient started treatment with nab-paclitaxel and he continues to have stable disease with no signs of disease progression for 18 months now. |
pmc-6501230-3 | A 77-year-old man was referred to an ocular oncologist in 2014 for visual changes in his right eye. He was diagnosed with a choroidal melanoma by histopathology and IHC, treated with I-125 plaque brachytherapy. Surveillance imaging in March 2017 showed liver and pulmonary lesions (M1a), with an LDH of 168 U/L and ALP of 54 U/L. A liver nodule biopsy confirmed the presence of MUM. The patient completed selective internal radiation therapy (SIRT) to the liver metastases in March 2017. In March 2017, the patient also started treatment with nivolumab (1 mg/kg) and ipilimumab (3 mg/kg) every 3 weeks for a total of four cycles, followed by nivolumab maintenance (240 mg). The patient also underwent TACE simultaneously with immunotherapy every 5–6 weeks starting from May 2017. Nivolumab was stopped in March 2018 due to thrombocytopenia, and the patient continued TACE every eight weeks until September 2018 and later discontinued due to no tumor growth. Repeat imaging in February 2019 showed stable disease. |
pmc-6501230-4 | A 76-year-old woman was referred to an ocular oncologist in 2014 for visual changes in her left eye and was diagnosed with a ciliochoroidal melanoma by histopathology, treated with I-125 plaque brachytherapy. Surveillance imaging in June 2017 showed multiple liver lesions with the largest measuring 4.5 × 3.5 cm (M1b). A liver biopsy confirmed MUM. The patient started therapy with nivolumab (1 mg/kg) and ipilimumab (3 mg/kg) every 3 weeks for four cycles, followed by maintenance nivolumab (240 mg) every two weeks simultaneously with TACE every 4 weeks. In October 2017, imaging showed stable liver lesions. Imaging surveillance in November 2017 showed the progression of the liver lesions, with an LDH of 466 U/L and ALP of 442 U/L. Nivolumab was discontinued in November 2017, and the patient expired in January 2018. |
pmc-6501230-5 | In 2014, a 65-year-old man was referred to an ocular oncologist for a visual change in his left eye and diagnosed with choroidal melanoma by histopathology and IHC, treated with enucleation, T1aN0M0. Surveillance imaging first showed hepatic lesions in January 2016. Active surveillance in August 2016 revealed that his liver lesions had increased in size and number with the largest lesion measuring 7.1 × 5.8 cm (M1b), with an LDH of 641 U/L and ALP of 111 U/L. Liver biopsy confirmed MUM. The patient started therapy with nivolumab (1 mg/kg) and ipilimumab (3 mg/kg) every 2 weeks simultaneously with TACE every 4 weeks in September 2016. A repeated abdominal magnetic resonance imaging (MRI) in November 2016 showed a marked decrease in the size and number of metastatic liver lesions (). After four cycles of nivolumab/ipilimumab, he started maintenance nivolumab (240 mg every 3 weeks) in January 2017. Repeat imaging showed continued response until August 2018. Imaging in September 2018 showed progression of disease; therapy switched to nab-paclitaxel. The patient currently has stable disease on nab-paclitaxel and TACE q8 weeks as of March 2019. |
pmc-6501230-6 | A 63-year-old man was initially referred to an ocular oncologist in February 2016 due to a visual change in his left eye. He was diagnosed with ciliochoroidal melanoma by histopathology, T4bN0M0. He was treated with enucleation of his left eye. In February 2017, surveillance imaging showed liver lesions, with the largest measuring 2.2 × 2.1 cm in hepatic segment 7 (M1a) and an LDH of 194 U/L, ALP of 94 U/L; biopsy confirmed metastatic melanoma. The patient started treatment with nivolumab (1 mg/kg) and ipilimumab (3 mg/kg) in May 2017. After two doses of a combination of ipilimumab and nivolumab, he developed colitis, which was treated with prednisone. Repeated imaging in June 2017 showed a decrease in the size of the metastatic hepatic lesion, from 2.2 × 2.1 to 1.7 × 1.5 cm (). The patient started nivolumab (240 mg every 2 weeks) in August 2017. In October 2017, imaging showed a mixed response, with stable lesions in segment 7 and new hepatic lesions in segment 8, with an LDH of 242 U/L, ALP of 114 U/L. The patient continued nivolumab until disease progression in April 2018, and the patient expired in June 2018. |
pmc-6501230-7 | A 73-year-old woman was referred to an ocular oncologist in June 2015 for visual changes in her right eye, diagnosed with a primary choroidal melanoma by histopathology. She was treated with I-125 plaque brachytherapy in June 2015. Surveillance imaging showed hepatic lesions in September 2015, with LDH of 194 U/L, ALP of 73 U/L. The largest lesion measured 2.2 × 2.2 cm (M1a). A liver biopsy confirmed MUM. She started therapy with nab-paclitaxel and received three cycles simultaneously with TACE for left and right liver lobe metastases. In February 2016, imaging showed disease progression, with LDH of 519 U/L and ALP of 72 U/L. Therefore, the patient started therapy with ipilimumab (3 mg/kg) and nivolumab (1 mg/kg). After one cycle, she developed grade IV myalgia and neuropathy requiring hospitalization and immunotherapy was stopped. In May 2016, the patient was initiated on pembrolizumab simultaneously with monthly TACE procedure for liver metastases. However, she was hospitalized for pulmonary edema and autoimmune hepatitis. Imaging repeated in September 2016 showed the progression of the hepatic lesions. She was later enrolled to hospice care and expired in September 2016. |
pmc-6501230-8 | A 55-year-old man was initially diagnosed with primary choroidal melanoma of the left eye in October 2016 by histopathology, treated with I-125 plaque brachytherapy. Surveillance imaging in July 2017 showed numerous liver lesions, the largest measuring up to 1.6 cm (M1a), with an increase in his LDH level to 634 U/L, ALP 65 U/L. A liver biopsy confirmed MUM. He started monthly TACE in August 2017. In September 2017, the patient started therapy with ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) every 3 weeks. He finished his fourth cycle in November 2017. In December 2017, an abdominal MRI showed a mixed response, in which several lesions were stable while others had slightly increased in size, with LDH level of 267 U/L and ALP 256 U/L. The patient later continued maintenance therapy with nivolumab (240 mg) every 2 weeks until January 2018. Repeat imaging in February 2018 showed disease progression and the patient expired in April 2018. |
pmc-6501231-1 | A 47-year-old HIV-negative female from northeast Africa was initially seen in consultation by the pulmonology service in 2007 for evaluation of positive TB skin test, abnormal chest X-ray (CXR) findings, and increasing symptoms of productive cough. She was a life-long nonsmoker, and her past medical history was significant for long-standing hypertension, osteoarthritis of the knee, and obesity. At the time, CXR demonstrated a density in the posterior left lower lobe and a poorly defined left hemidiaphragm. Bronchoscopy showed no obvious endobronchial abnormalities noted. Washings from the left upper and lower lobes consisted of negative cultures and negative acid-fast bacilli (AFB) analysis. Cytological analysis yielded a few multinucleated giant cells. CT of the chest demonstrated an enlarged right pulmonary artery and a slightly enlarged right atrium, with associated radiographic abnormalities of the left lung, including multifocal areas of consolidation, subpleural ground glass opacities and reticulation, and bronchiectasis. More notably, there was evidence of hypertrophied bronchial arteries providing collateral circulation to the left lung (Figures and ).
The patient was lost to follow-up and seen again in 2015, at the age of 55, for evaluation of chronic pulmonary infiltrates, accompanied by symptoms of fever, cough, copious watery sputum production, low-volume hemoptysis, decreased exercise tolerance, and left-sided chest pain. Repeat CT scan examination confirmed absence of the left pulmonary artery with near complete consolidation of the left lung, as well as left-sided mediastinal shift and a small left pleural effusion. The right lung contained multifocal nodular opacities in all lobes (Figures and ). Given the radiographic and clinical changes, the patient was thought to have a primary infectious process (likely MTB complex) and was placed on respiratory isolation. Repeat bronchoscopy was performed with no growth of tuberculosis or other infectious agent and persistently negative AFB. The presumed diagnosis at that time was infectious vs. inflammatory in nature, with a remote possibility of malignancy still being considered. A thoracic surgical consultation was sought out, for consideration of open lung biopsy as a means of ruling out malignancy and to consider left pneumonectomy for symptom control.
The patient's symptoms ultimately continued to increase, requiring admission to a hospital for supplemental oxygen delivery. Transthoracic and surgical biopsies were deemed to be too highly risky and were ultimately not pursued. Despite aggressive medical therapy and broad spectrum antibiotic coverage, she required transfer to the intensive care unit due to hypoxic respiratory failure. Multidisciplinary conferencing concluded that the necrotic left lung was the primary culprit in the patient's decline, with acute chronic infection likely related to right lung contamination being the most likely diagnosis. The patient continued to decline clinically. She developed multisystem organ failure including respiratory compromise leading to intubation and mechanical ventilation, hypotension requiring ionotropic support, and worsening renal function. Accordingly, the decisive treatment option was for an emergent high-risk left pneumonectomy with consideration of preoperative embolization of collateral hypertrophied bronchial vessels. Preoperative CT investigation demonstrated a consolidated necrotic left lung, with moderate left pleural effusion and areas of thickening of the left pleura. On cardiopulmonary testing, echocardiogram revealed left-sided ejection fraction of 65-70%, with preserved right ventricular systolic function, without any significant tricuspid regurgitation. Quantitative lung ventilation-perfusion scanning identified 1% ventilation and perfusion to the left lung, with >90% right-sided lung perfusion. The patient and her family were quoted a near 50-90% surgical mortality, in the face of imminent death without intervention.
The patient was taken to the operating room and placed in the right lateral decubitus position, and an endobronchial blocker was placed through her single-lumen endotracheal tube and positioned in the left mainstem bronchus. A posterolateral thoracotomy was performed, after harvesting a serratus anterior muscle flap. Upon entry into the pleural space, it was evident that the left lung was cemented to the parietal pleura with dense thick adhesions. Minimal dissection was undertaken in order to identify an area of the pleural cavity that was free. Five hundred milliliters of serous pleural fluid was drained. Additionally, there was evidence of multiple small pleural nodules dispersed throughout the chest cavity and the hilum. Frozen section analysis of these pleural deposits confirmed the presence of metastatic adenocarcinoma, confirming the presence of stage IV lung cancer. As such, the planned left pneumonectomy was aborted and the chest was closed with an indwelling chest tube.
She was transferred back to the ICU with continued mechanical ventilation. The working diagnosis at that point was diffuse metastatic lung cancer with lymphangitic carcinomatosis and superimposed infection. After the family was informed of the operative findings, a palliative approach was undertaken. Comfort measures were ensured. Mechanical ventilation was weaned off as care was being withdrawn, and the patient peacefully passed away.
Pleural fluid analysis identified the presence of malignant cells suggestive of adenocarcinoma. Final pathologic analysis of intraoperative specimens demonstrated pleural tissue comprised of tall columnar tumor cells with focal necrosis, infiltrated by adenocarcinoma (thyroid transcription factor-1 positive) with predominantly papillary features. Epidermal growth factor receptor (EGFR) mutation was not identified (wild-type allele) by polymerase chain reaction (PCR) analysis using the EntroGen EGFR Kit Exons 18, 19, 20, and 21. In addition, ALK rearrangement was not identified. |
pmc-6501235-1 | A 15-year-old Caucasian female presented with an intra-articular fracture and adjacent laceration at the distal portion of the proximal phalanx of the thumb resulting in near complete loss of the interphalangeal joint (Figures and ). The injury was incurred from a table saw accident. The patient had an initial pain level of 4/10 and was unable to flex her thumb. The patient and her family were offered a joint arthrodesis for joint stability, but they did not desire a fusion. The patient felt a fusion would limit activities important to her such as texting, playing video games, and applying cosmetics. Joint replacement was offered to the patient as an alternative treatment. In the present case, an HUD was utilized in an off-label manner and inserted into the interphalangeal joint of the patient's thumb. The patient and family were counseled that this was not a standard treatment option and that if fusion was needed in the future, it could be more complicated and require bone grafting compared to using fusion as the initial alternative.
The patient was followed for 22 months postoperatively and has remained happy with her choice of procedure. The patient's motion in the thumb IP joint is currently a 40 degree arc which is very reasonable given the repair of the flexor pollicis longus tendon and collateral ligament as well. There was excellent range of motion (ROM) in the metacarpophalangeal joint (MCP) which is comparable to the contralateral side. Radiographs demonstrated good seating of the joint implant with no evidence of loosening or periprosthetic fracture (Figures and ). The collateral ligaments were all stable at the IP joint, and the scar on the left volar thumb was well-healed. The patient reported pain of 0/10 at her most recent follow-up and recorded a DASH score of 6.82. No known complications have arisen as a result of the surgical reconstruction to this point in time. |
pmc-6501236-1 | A 38-year-old man with homozygous SCD presented to the emergency department with a sickle cell vasoocclusive pain crisis. On presentation, he reported one day of worsening midsternal chest pain and lower back pain. His initial workup was notable for normal vital signs, hemoglobin of 10.7 g/dL (baseline: 12.0 g/dL), absolute reticulocyte count of 374 k/μL, creatinine of 1.16 mg/dL, lactic acid of 1.5 mmol/L, undetectable troponin, and initial chest radiograph with clear lungs.
On further chart review, he had a history of remote pulmonary embolism and was on life-long warfarin therapy and a history of precapillary PH. Echocardiogram twenty-two months prior to admission showed a moderately enlarged RV with mildly reduced function and estimated pulmonary artery systolic pressure (ePASP) of 60 mmHg (). Right heart catheterization (RHC) nineteen months prior to admission showed mild precapillary PH (). Pulmonary function testing showed forced expiratory volume in one second (FEV1) 72% predicted, forced vital capacity (FVC) 83% predicted, FEV1/FVC 71% predicted, and corrected diffusion capacity 45% predicted. A sleep study showed nocturnal desaturations and an apnea hypopnea index of 9.5, and he was placed on continuous positive airway pressure with supplemental oxygen at night. His PH was felt to be multifactorial given his history of SCD, mild obstructive sleep apnea and nocturnal hypoxia, and prior pulmonary embolism.
Following admission, he was started on intravenous fluids and opiates. On hospital day two, his oxygen saturation dropped to 83% and blood pressure to 76/55 mmHg. Arterial blood gas on 6 L/min of oxygen via nasal cannula showed a partial pressure of arterial oxygen (PaO2) of 65 mmHg. He was placed on high-flow nasal cannula at 40 L/min and 50% fraction of inspired oxygen with improvement in PaO2 to 105 mmHg. Laboratory workup was notable for hemoglobin 8.5 g/dL, reticulocyte count 349 k/μL, 55.2% hemoglobin S, lactic acid 5.0 mmol/L, lactate dehydrogenase 528 U/L, total bilirubin 1.4 mg/dL, creatinine 1.41 mg/dL, brain natriuretic peptide 586 pg/mL, and troponin 4.09 ng/mL. Chest radiograph showed slight left greater than right suprahilar opacities (), and computed tomography angiogram did not demonstrate a pulmonary embolism. Echocardiogram revealed a severely enlarged RV with severely reduced systolic function and an ePASP of 132 mmHg (). There was concern for ACS. The patient received empiric vancomycin, meropenem, and azithromycin and underwent exchange transfusion of three units packed red blood cells with improvement in hemoglobin S to 26%. Despite these therapies, he had worsening hypotension over the following twenty-four hours, including requiring up to three vasopressors (norepinephrine, vasopressin, and epinephrine). Cardiology was consulted and, given the unclear etiology of his decompensation, a RHC with a retained pulmonary artery catheter was rapidly performed and demonstrated severely decompensated precapillary PH, acute RV failure, and cardiogenic shock ().
He was diuresed and started on dobutamine. Given his predominantly precapillary PH on RHC, he was also initiated on inhaled epoprostenol to allow for RV afterload reduction and avoid intubation (which was considered extremely high risk). He initially showed rapid improvement and was weaned from epinephrine and vasopressin in the following twelve hours. However, he failed to improve further despite effective diuresis, normal oxygenation, empiric antibiotics, and additional exchange transfusions. He continued to require high-dose dobutamine and inhaled epoprostenol for the following four days. Cardiac index, calculated by the indirect Fick method using a central venous catheter, remained 1.7-1.9 L/min/m2, and attempts to wean inotropic support resulted in hypotension. After several days of inability to wean dobutamine, it became clear that he was in persistent RV failure. Alternative therapies were considered to decrease RV afterload and allow for downtitration of inotropic and inhaled vasodilator support.
Phosphodiesterase inhibitors were avoided due to evidence of increased adverse effects in patients with SCD []. Endothelin receptor antagonists were avoided because of their potential to cause anemia and fluid retention, especially given the patient's low hemoglobin, active hemolysis, and decompensated heart failure. Intravenous therapies were considered, although they are not available at our institution and transfer to a tertiary center was declined.
Given that the patient had responded well to inhaled epoprostenol, it was felt that an oral agent acting upon the prostanoid pathway was appropriate to trial. We reviewed the literature and found that rapid uptitration of selexipag had been safe in healthy subjects and patients with PH [–]. Ultimately, he was initiated on rapidly uptitrated doses of selexipag, reaching target dosing of 1600 μg twice daily over fifteen days. During the rapid uptitration, the patient denied symptoms associated with prostacyclin intolerance. Two days after initiation of selexipag, cardiac index improved to greater than 2 L/min/m2, and right atrial pressure decreased to less than 10 mmHg; eight days after initiation, he was able to be weaned completely from dobutamine and epoprostenol. He was discharged on hospital day 21 and followed up in the cardiology clinic twice in the following year without further episodes of ACS or RV failure. Follow-up echocardiogram ten months after hospitalization on selexipag and macitentan showed improved RV size and function with ePASP 45 mmHg (). |
pmc-6501238-1 | A 79-year-old man with a medical history of hypertension, stage G3b chronic renal insufficiency, and interstitial lung disease presented with a four-month history of progressive dyspnoea (NYHA III).
Transthoracic echocardiography showed a bicuspid aortic valve (BAV) (Figures and ) with severe, paradoxical, low-flow, low-gradient (mean gradient 26 mmHg) AS, a calculated aortic orifice area of 0.78 cm2, and a preserved left ventricular ejection fraction of 55%. A coronary angiogram revealed no significant epicardial coronary stenosis. Aortic root assessment was completed by multidetector computed tomography (MDCT), which revealed severe aortic annular calcification, with an aortic valve calcium score of 10133 AV and a large aortic valve annulus (Figures and ). After using the three multiplanar reformation planes, measurements were derived from the area as well as the circumference of the virtual basal ring (mean diameter: 30.4 mm, annular area: 726.9 mm2, perimeter: 93.38 mm, long axis: 33.9 mm, and short axis: 26.2 mm). MDCT did not reveal any calcification extending into the left ventricular outflow tract. Additional supra-annular measurement of the valve opening area at the level of the maximal calcification did not show a significant mismatch compared with the initial measurements. Based on his severe comorbidities, characteristics of frailty, and refusal of surgery, the heart team decided to perform a TAVI via a femoral approach.
Balloon aortic valvuloplasty was performed using a 28 mm × 4 cm Nucleus balloon (NuMED, NY). Given the aspect of the valve marked by a large annulus with severe annular calcification and the eventual benefit of a valve resheathing and optimised repositioning, a CoreValve Evolut R 34 mm (Medtronic Inc., MN, USA) was implanted. After valve deployment, fluoroscopy and transoesophageal echocardiography (TEE) (Figures and ) revealed a PVL due to (i) suboptimal valve expansion because of interference with the valvular ring by nodular calcifications and (ii) low positioning of the aortic valve prosthesis. The patient showed signs of haemodynamic instability, necessitating the initiation of inotropic support.
Our initial approach included postdilatation with the largest balloon available in our catheterization laboratory (28 mm × 4 cm Nucleus balloon (NuMED, NY)), attempting a better valve expansion and sealing the paravalvular space. However, fluoroscopy and TEE showed no improvement to the PVL (). Among the possible strategies, percutaneous valvular closure using Amplatzer plugs constitutes a viable alternative in patients developing a PVL after TAVI [, ]. After an urgent discussion, the heart team decided to proceed with paravalvular implantation of a cardiac plug in an attempt to seal the PVL and improve the patient's haemodynamic status. After measuring the size of the leak by TEE, a Terumo wire (Terumo Interventional Systems, Somerset, New Jersey) was easily pushed through the aortic prosthesis struts, and the first 12 mm Amplatzer Vascular Plug II (AVPII) (AGA Medical Corp., Plymouth, Minnesota) was successfully implanted. Before detachment, coronary permeability was verified by coronary angiography. However, this failed to reduce the severity of the PVL. Following the same procedure as previously, we decided to implant a second 10 mm AVPII (Figures and ) (AGA Medical Corp., Plymouth, Minnesota), which was positioned parallel to the first one. Again, fluoroscopy and TEE did not show any significant reduction in the PVL (), and the patient remained haemodynamically unstable requiring continuous inotropic therapy.
We decided to proceed with a TAV-in-TAV implantation as a rescue procedure, using a second aortic prosthesis (29 mm EDWARDS Sapien 3, Edwards Lifesciences, Irvine, California). This was deployed within the first valve (), and the final outcome was the elimination of the AS, the sealing of the PVL, and the presence of a mild residual aortic regurgitation (Figures and , ).
Nevertheless, a final aortic root angiography revealed a type A aortic dissection arising in the aortic sinuses and extending into the ascending aorta. The permeability of the coronary arteries was intact, and no pericardial infusion was observed. After a multidisciplinary discussion, a conventional surgical intervention was proposed to the family, but they refused this option. Continuation of all resuscitation therapy was abandoned, and the patient died three days later. |
pmc-6501246-1 | A 5-year-old boy presented to the Department of Pediatric Dentistry of the Faculty of Dental Medicine at Saint-Joseph University of Beirut, Lebanon, with a chief complaint of loosening of all primary teeth, followed by their spontaneous loss. The patient's medical history showed that he was undergoing a dermatological treatment for the “hyperkeratosis of his palms and soles”; the treating dermatologist referred the patient to the dentist after having suspected PLS. A detailed family history revealed that the patient's parents, grandparents, and relatives were consanguineously married and two of his cousins exhibited similar clinical signs (palmoplantar hyperkeratosis and premature loss of deciduous and permanent teeth).
Intraoral examination revealed that many primary teeth (teeth 54, 52, 51, 61, 62, 64, 74, 72, 71, 81, and 82) were missing while remaining teeth (teeth 85, 84, 83, 73, 75, 65, 63, 53, and 55) exhibited plaque accumulation, multiple caries, and generalized grade III mobility with the formation of periodontal pockets (); gingival tissues surrounding these teeth were inflamed, edematous, and tender to palpation, while those of edentulous regions appeared normal and nontender to palpation. Dental and periodontal abscesses were noticed on teeth 85 and 75. Panoramic radiograph displayed several floating teeth with generalized horizontal and vertical bone loss ().
Extraoral examination of the patient revealed hyperkeratosis on the dorsum surface of his hands () and feet ().
Routine hematological examination (CBC and blood chemistry profile) and liver function tests were normal. In addition, a genetic test was performed at the Saint Joseph University Faculty of Medicine/Laboratory of Molecular Biology, Beirut; PCRs (polymerase chain reaction) followed by fluorescent Sanger sequencing of exons 3 to 7 of CTSC gene, for the affected child, revealed no mutation. However, PCR amplification of exons 1 and 2 did not result in any product, suggesting that affected child harbored a homozygous deletion of the 5′UTR region and exons 1 and 2.
Level of patient's cooperation was assessed during the first clinical examination, and it was decided to implement the treatment under general anesthesia, at hospital. A written informed consent form was signed by the child's parents after having discussed with them all the steps of the treatment planning, from extraction of all remaining teeth to the fabrication of an immediate removable complete denture (RCD). The importance of oral hygiene was emphasized, and enforcement of oral hygiene habits was advocated.
At hospital, the first dose of amoxicillin (50 mg/kg) and clavulanic acid was administered through IV route before beginning the surgery and it was continued for the following postoperative seven days. In order to maintain a stable occlusion, two impressions of maxilla and mandible were taken with the remaining teeth in place using an addition silicon material. All remaining teeth were extracted, and all extraction sockets were irrigated with a 0.12% chlorhexidine digluconate solution. No sutures were needed, and impressions were directly transferred to the dental laboratory in order to be casted.
Two weeks after extractions, maxillary and mandibular RCDs were fabricated () and inserted in the mouth (). No pressure spots were noticed, and occlusion showed no interferences. Patient and parents were taught the proper oral hygiene measures for RCDs; they were also informed of the need for regular dental visits (one week after the insertion and every three months afterwards) in order to reexamine the appliances and, when necessary, replace or reline them according to arch growth and eruption of the permanent teeth. Eight-month follow-up revealed the erupting mandibular central incisors (). |
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.