Effect of L‑arginine supplementation on homocysteine and asymmetric dimethylarginine in atherosclerotic lower limb ischemia

Abstract: Chronic lower limb ischemia is a manifestation of systemic atherosclerosis frequently accompanied by lipid metabolism disorders, endothelial dysfunction, and disturbances in the L-arginine-nitric oxide (NO) pathway. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, and homocysteine (Hcy) are recognized markers of vascular risk. This study aimed to evaluate the effect of 2 months of oral L-arginine supplementation (6g/day) on serum ADMA and Hcy concentrations in patients with atherosclerotic lower limb ischemia, depending on lipid metabolism disorder type. In a randomized, double-masked, placebo-controlled trial, 87 patients (50 men, 37 women) were assigned to L-arginine or placebo. Subgroups were defined according to lipid abnormalities: hypertriglyceridemia, hypercholesterolemia, and mixed hyperlipidemia. ADMA was measured by HPLC, and Hcy by fluorescence polarization immunoassay at baseline, 30, and 60 days. L-arginine supplementation significantly reduced ADMA levels in patients with hypercholesterolemia after 30 and 60 days (P<0.05) and in those with mixed hyperlipidemia after 60 days (P<0.05), but not in those with isolated hypertriglyceridemia. Changes in Hcy were not statistically significant. A significant positive correlation between ADMA and Hcy was present in all subgroups, most consistently in hypercholesterolemia. Two-month L-arginine supplementation decreases ADMA concentrations in patients with atherosclerotic lower limb ischemia, with efficacy dependent on the underlying lipid disorder phenotype, suggesting a metabolism-specific modulation of the ADMA-NO axis.

Micker M
Balcer-Dymel N
Pruszynska-Oszmalek E
Madej-Czerwonka B
Leciejewska N
Kolodziejski P
Sassek M
Grzeda E
Checinska-Maciejewska Z
Jaskula M
Krauss H
Rekas-Dudziak A

Humans
Arginine
Homocysteine
Female
Male
Atherosclerosis
Ischemia
Dietary Supplements
Middle Aged
Double-Blind Method
Aged
Lower Extremity
Hypercholesterolemia
Hyperlipidemias


Developing and evaluating an in situ, simulated emergency training course for nurses with low seniority

Abstract: This study aimed to construct and implement an in situ simulated emergency training (SET) course for nurses with low seniority and evaluate its effectiveness. This was an experimental study, and a purpose-sampling method was adopted. We selected 82 nurses with less than 5 years of experience working in a grade - III Class A hospital in Hubei province from August to December 2023 as the research objects, and randomly divided them into intervention group (n = 37) and control group (n = 45). The control group underwent routine stratified training, whereas the intervention group underwent in situ SET based on routine stratified training. Before and after training, we compared differences in the scores of the intervention and control groups in terms of critical thinking (CT), clinical communication (CC), clinical reasoning (CR), and first aid (FA). The constructed in situ simulated emergency training course consisted of nine courses, each of which covered one theme. The nine themes were acute myocardial infarction, diabetic ketoacidosis, secondary shock due to acute transfusion anaphylaxis, post-operative respiratory depression combined with pulmonary edema, unplanned extubation, impulsive violence, chemotherapeutic drug extravasation, patient suicide, and acute pulmonary embolism. The results of the empirical study showed that before training, there were no differences between the intervention and control groups in the scores for the following abilities: CT, CC, CR, and FA (p > 0.05). After training, the scores for CR and FA in the intervention group were higher than those in the control group (p < 0.05), while the scores for CT and CC did not differ from those in the control group (p > 0.05). The content of the in situ SET course is comprehensive, which is helpful in improving junior nurses' CC and FA abilities and can serve as a reference for establishing a training course for them. However, the effects on the CT and CC were not significant. Further empirical studies are required to explore the targeted training courses.

Shen M
Tan X
Xianyu Y
Chen Q
Fang Y
Zeng C
Yang G
Pan M
Cai Z

Humans
Clinical Competence
Female
Simulation Training
Adult
Male
China
Nursing Staff, Hospital

Journal Article
Randomized Controlled Trial


Assessment of classification accuracy in endodontics by dental students: a comparative study of holographic imaging and conventional radiography

Abstract: Dental students must master endodontic anatomy, radiographic diagnostics, and treatment strategies early in their clinical training-yet traditional teaching methods, including two-dimensional radiographs, often fail to effectively convey complex spatial structures. Hologram technology has emerged as a promising tool for three-dimensional visualization in dental education. The aim of the study was to compare the classification accuracy of dental students using holograms versus conventional periapical radiographs in identifying endodontic structures. This randomized single center-controlled trial included 79 dental students (years 4-6). After a calibration seminar and pre-test each of the 79 students assessed six tooth cases-three presented as holograms and three as periapical radiographs. Holograms were created from cone-beam computed tomography data, annotated by two calibrated examiners to establish reference points regarding the number of canals, Vertucci classification, and treatment complexity. Students evaluated each case for these parameters; responses were compared to the reference points to assess classification accuracy. The final evaluation form captured their subjective perceptions of the new hologram system. Primary binary outcomes were analyzed using logistic mixed-effects models. P-values were adjusted for multiple testing using the Benjamini-Hochberg procedure. Statistical significance was set at p < 0.05. After Benjamini-Hochberg correction, holography significantly improved root-canal number identification in three multi-rooted cases (adjusted p ≤ 0.007). For Vertucci classification, only the maxillary anterior tooth remained significant (adjusted p = 0.044). Treatment-complexity assessment showed case-dependent results, favoring radiography in two cases (adjusted p = 0.045 and p = 0.006) and holography in one case (adjusted p = 0.013). Holographic visualization demonstrated case- and task-specific effects in endodontic training. Holograms were able to improve classification accuracy in certain endodontic tasks. However, they did not outperform conventional periapical radiographs in all outcomes. Holography could be an effective, supplementary tool for teaching certain endodontic tasks, but its application requires further investigation. The study was prospectively registered in the German Clinical Trials Register (DRKS-ID: DRKS00035000) on 13.09.2024.

Lederer ML
Barbe AG
Janson M
von Kohout M
Schoppmeier CM

Humans
Holography
Endodontics
Students, Dental
Cone-Beam Computed Tomography
Education, Dental
Imaging, Three-Dimensional
Clinical Competence
Female

Journal Article
Comparative Study
Randomized Controlled Trial


Motivational Coaching Cues Can Modulate Prefrontal Cortex Activity and Perceptual Responses of Elite Football Players During High-Intensity Interval Training: A Randomised Crossover fNIRS Study

Abstract: Football coaches commonly provide verbal encouragement and exercise end-point feedback to sustain players' effort by enhancing motivation during fitness training such as high-intensity interval training (HIIT). However, the influence of such cues on the prefrontal cortex (PFC), a region involved in exercise cessation decisions, remains unclear. Therefore, this study aimed to compare the effect of motivational cues on PFC activation during HIIT using functional near-infrared spectroscopy, alongside physiological and perceptual responses. Twenty-two male elite footballers completed two randomised crossover HIIT sessions on a cycle ergometer, with and without motivational cues. Each session consisted of 12 repetitions of 30-s high-intensity bouts, each interspersed with a 30-s active recovery bout. Heart rate, lactate concentration, rating of perceived exertion (RPE), motivation-related questionnaires and oxygenated haemoglobin (HbO2) concentration in the PFC were measured throughout HIIT. Although physiological responses were similar between conditions, perceived difficulty, assessed every three HIIT bouts, was significantly lower under the motivational condition, with lower RPE (p = 0.038) and higher motivation (p = 0.049), engagement (p = 0.038) and mood (p = 0.009) scores, particularly after the 9th repetition. From the 10th to 12th repetition of HIIT, the HbO2 concentrations of the orbitofrontal cortex and frontopolar PFC were significantly lower under the motivational condition (p = 0.040 and p = 0.036, respectively), whereas the dorsolateral and ventrolateral PFC showed no significant difference between conditions. In conclusion, motivational cues reduce central PFC activity during the most fatiguing phases of HIIT, reflecting enhanced neural efficiency under motivation despite equivalent physical workloads.

Han S
Ahn S
Sung Y
Seo JW
Li X
Han S
Kim C
Song W

Humans
Prefrontal Cortex
Male
High-Intensity Interval Training
Cross-Over Studies
Motivation
Spectroscopy, Near-Infrared
Young Adult
Cues
Soccer
Heart Rate
Physical Exertion
Adult
Lactic Acid
Athletes


Treatment of striae albae with combination of fractional radiofrequency and topical tretinoin: A randomized controlled trial

Abstract: Mature striae distensae, called striae albae, are common but treatment-resistant dermal scars. Fractional radiofrequency (FRF) can potentially act as transdermal permeation enhancer for topical tretinoin (TT). This study investigated FRF and TT as a combination treatment for striae albae. Twenty patients were included, each with four anatomically comparable areas that were randomized to (i) TT (ii) FRF (iii) combination FRF + TT and (iv) untreated control. Three treatment sessions were performed one month apart, and TT was also applied in-between. The change in striae from baseline to 20-week follow-up (Δ) was assessed using the Patient Observer Scar Assessment Scale (POSAS, SUM: 6-60). At baseline, patients assessed the striae as moderate-severe (POSAS-PT: SUM medians 24-25) and at follow-up, they reported an improvement (POSAS-PT: ΔSUM 5-10 points), but only the combination treatment improved significantly better (FRF + TT vs. control p = 0.029). A blinded dermatologist confirmed a tendency towards treatment improvement (POSAS-OBS: ΔSUM: 0-2 point, all treatments vs control p≥0.269). A subtle tendency was observed in objective measures with 3D photographs. Combination treatment with FRF and TT was tolerable and improved patient-reported striae compared to control. Striae albae remain challenging, but the findings highlight a potential for future combination treatment approaches.Trial registration number: NCT05461755Date of registration: 15.07.2022.

Grove GL
Karmisholt KE
Philipsen PA
Bjerring P
Haedersdal M

Humans
Tretinoin
Female
Striae Distensae
Male
Middle Aged
Combined Modality Therapy
Adult
Treatment Outcome
Keratolytic Agents
Administration, Cutaneous
Radiofrequency Therapy


Comparative efficacy of an 8-week core stability program versus foot-ankle strengthening on pain, function, and distal structural parameters in individuals with knee osteoarthritis: a randomized controlled trial

Abstract: Knee osteoarthritis (OA) is a common musculoskeletal condition linked to aberrant joint loading, pain, and reduced function. While effective rehabilitation should target both local knee problems and the entire kinetic chain, direct comparisons between proximal (core stability) and distal (foot-ankle) interventions are limited. This randomized controlled trial evaluated the efficacy of an 8-week core stability exercise (CSE) program versus foot-ankle strengthening (FAS) in individuals with knee OA. One hundred participants (aged ≥ 40 years, Kellgren-Lawrence grade II-III) were randomly assigned to either CSE (n = 50) or FAS (n = 50). Both groups performed conventional knee exercises three times weekly for 8 weeks, supplemented by their respective group-specific training. The primary outcome was resting pain intensity evaluated via a visual analogue scale (VAS). Secondary outcomes included the Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales, functional performance tests (40-m fast-paced walk, 30-second chair stand, and 11-step stair climb), and distal structural measures (Achilles tendon thickness and navicular/foot ratio). Assessments were conducted at baseline and after 8 weeks, with between-group differences analyzed using ANCOVA adjusted for baseline values. The CSE group showed significantly greater improvements across all outcomes compared to the FAS group. Between-group differences exceeded validated minimal clinically important differences (MCID) for resting pain and all KOOS subscales, met MCID thresholds for the walk and chair-stand tests, and safely surpassed minimal detectable changes (MDC) for the stair-climb test and distal structural parameters; large effect sizes favored core stability training. These findings indicate that proximal core stabilization added to conventional knee exercises provides superior short-term improvements in functional mobility and distal structural surrogates compared to foot-ankle strengthening combined with conventional knee exercises in knee OA rehabilitation. Crucially, these static distal structural modifications are exploratory, likely reflecting localized soft-tissue fluid shifts rather than permanent anatomical remodeling, and demand future validation via advanced diagnostic imaging.Trial Registration: ClinicalTrials.gov ID= NCT06766877 (registered 9 January 2025).

Humans
Osteoarthritis, Knee
Female
Middle Aged
Male
Exercise Therapy
Aged
Foot
Treatment Outcome
Pain Measurement
Ankle
Ankle Joint
Pain
Resistance Training
Muscle Strength

Journal Article
Randomized Controlled Trial
Comparative Study


Maintenance of clinical remission with cyclosporine after discontinuation of prednisolone in a patient with tubulointerstitial nephritis with IgM-positive plasma cells

Abstract: Tubulointerstitial nephritis (TIN) with IgM-positive plasma cells (IgMPC-TIN) is an inflammatory disease characterized by the infiltration of IgM and CD138 dual-positive plasma cells into the renal interstitium. Steroid treatment is effective for many cases of IgMPC-TIN. However, the optimal dose and duration of steroid therapy remain poorly understood. In the present case, IgMPC-TIN was diagnosed in a 36-year-old woman with femoral head osteonecrosis. After administration of prednisolone (PSL, 20 mg/day), several markers of disease activity gradually decreased. The PSL dose was tapered to 5 mg/day for one year without TIN recurrence. To avoid exacerbation of bone lesions due to prolonged administration of PSL, cyclosporine was added to PSL. Combination treatment with 5 mg/day PSL and 100-125 mg/day cyclosporine stabilized the TIN. The patient remained stable without recurrence after further reduction and discontinuation of PSL. This case provides original evidence regarding the optimal treatment regimen for patients with IgMPC-TIN who are unsuitable for prolonged PSL administration.

Yamada K
Nakao S
Ikeda M
Suetsugu-Ishizawa R
Hayashi N
Sakuma H
Matsuki M
Takahashi N
Iwano M
Toyama T
Ogawa Y
Nakagawa N

Humans
Female
Nephritis, Interstitial
Cyclosporine
Prednisolone
Adult
Immunoglobulin M
Plasma Cells
Immunosuppressive Agents
Treatment Outcome
Drug Therapy, Combination
Remission Induction


Dosing challenges for chemotherapy and immunotherapy in congenital achondroplasia: a case report and literature review

Abstract: Currently, no established guidelines exist for dosing chemotherapy or immunotherapy in patients with achondroplasia. A 69-year old female with congenital achondroplasia was diagnosed with stage IV non-small cell lung carcinoma type adenocarcinoma, with high Tumor Mutational Burden and 20% programmed death-ligand 1 expression. The patient received carboplatin dose based on renal function utilizing measured creatinine clearance, pemetrexed based on body surface area and pembrolizumab at a fixed dose of 100mg for body weight <65 kg. The doses of carboplatin and pemetrexed were adjusted after the first cycle based on therapeutic drug monitoring (TDM). The treatment was generally well tolerated, with the exception of grade 2 neutropenia, which resolved after a one-week delay of the third treatment cycle. A favorable clinical response was achieved after four treatment cycles. Given the uncertainty regarding the accuracy of dosing algorithms in patients with congenital achondroplasia, TDM may support dose optimization and attainment of adequate drug exposure.

Groot Beumer KWM
Durlinger EMJ
Zielhuis SWJ
Ter Heine R
Huitema ADR
Hendrikx JJMA

Antineoplastic Combined Chemotherapy Protocols


A rare variant in DPYD c.812delT causes severe adverse events of S-1 in a patient with tongue cancer

Abstract: Dihydropyrimidine dehydrogenase (DPD), which is encoded by the DPYD gene, plays an important role in the metabolism of fluoropyrimidine (FP) drugs, including tegafur, in S-1. A decrease in DPD activity can cause severe FP-related toxicity. The Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for FP and DPYD polymorphisms recommend FP dose adjustments based on the four major DPYD polymorphisms. However, multiple rare variants of DPYD have been reported. We present the case of a man in his 50s with cT3N0M0 tongue squamous cell carcinoma who developed severe myelosuppression and diarrhea after the initiation of S-1 (tegafur/gimeracil/oteracil) despite appropriate dosing. On day 20 of treatment, the patient developed grade 4 neutropenia and septic shock and required ICU admission. Genetic testing identified a rare heterozygous DPYD variant (c. 812delT) that causes a frameshift and a presumed loss of enzyme function, suggesting an underlying cause of the severe adverse events. Although severe toxicity occurred, marked tumor shrinkage allowed for less invasive surgery. This case highlights the need for expanded genetic screening beyond the guideline-listed variants, particularly in Asian populations, where common variants differ. Combining genotypic and phenotypic evaluations of DPD activity may improve the prediction and prevention of FP-related toxicities, supporting safer and more effective use of FP drugs.

Ishimura H
Suehiro A
Hira D
Hishinuma E
Kato M
Maekawa M
Yasuda T
Katsube Y
Katada Y
Imayoshi N
Shigetsura Y
Nakagawa S
Tsuda M
Hiratsuka M
Terada T

Humans
Tegafur
Male
Dihydrouracil Dehydrogenase (NADP)
Oxonic Acid
Tongue Neoplasms
Drug Combinations
Middle Aged
Antimetabolites, Antineoplastic
Carcinoma, Squamous Cell


Early identification of LPIN1 variant in a child with severe myoglobinuria and a history of sibling deaths

Abstract: Rhabdomyolysis in children is frequently attributed to viral myositis or trauma; however, severe or recurrent episodes precipitated by febrile illnesses often indicate an underlying genetic myopathy. Variants in the LPIN1 gene, which encodes the phosphatidic acid phosphatase Lipin-1, have recently emerged as a major cause of early-onset, life-threatening rhabdomyolysis (Autosomal Recessive Acute Recurrent Myoglobinuria). We present the case of a 5-year-old female who presented with acute onset profound lethargy, generalized muscle weakness, and cola-colored urine following a viral prodrome, on a background of previous similar milder episodes. The patient's family history was significant for consanguinity and the unexplained deaths of two siblings at similar ages. Laboratory investigations revealed massive rhabdomyolysis with a creatine phosphokinase (CPK) level of 59,679 U/L and significant myoglobinuria, though renal function remained initially preserved. Given the severity of the presentation and family history, comprehensive genetic investigation was pursued. Whole Exome Sequencing (WES) of a similarly affected younger sibling, followed by targeted familial screening, identified a homozygous variant in the LPIN1 gene; NM_001349206.2: c.2360_2361delinsGA p.(Pro787Arg) in our patient. The patient was managed conservatively with vigorous hydration and alkalinization of urine, resulting in clinical improvement without the development of acute renal failure. LPIN1 deficiency is a critical differential diagnosis in pediatric patients presenting with unexplained, massive rhabdomyolysis, particularly in the context of consanguinity or a history of sibling mortality preceded by muscle weakness. This case highlights the utility of Whole Exome Sequencing post-stabilization to establish a strong molecular basis for the diagnosis, which terminates the diagnostic odyssey and is essential for providing genetic counseling to affected families.

Humans
Female
Phosphatidate Phosphatase
Myoglobinuria
Child, Preschool
Rhabdomyolysis
Siblings
Exome Sequencing
Consanguinity
Pedigree
Creatine Kinase
Homozygote


Renal cysts in WDR72-associated distal renal tubular acidosis: expanding the phenotypic spectrum

Abstract: Pathogenic variants in the WDR72 gene are known to cause hypoplastic amelogenesis imperfecta (AI) and have recently been linked to distal renal tubular acidosis (dRTA). This case report highlights an unusual presentation of WDR72-associated dRTA with renal cysts. A 12-year-old boy presented with difficulty walking, lower limb deformities, and significant growth retardation. On examination, hypoplastic AI, rickets, and short stature were present. Biochemical investigations showed hypokalemia, hypophosphatemia, elevated alkaline phosphatase, and hypercalciuria. Imaging revealed medullary nephrocalcinosis and renal cysts. Clinical exome sequencing identified a homozygous pathogenic nonsense variant in WDR72 (NM_182758.4): c.2934G > A (p.Trp978Ter), consistent with autosomal recessive inheritance. He was diagnosed with dRTA and managed with potassium citrate and phosphate supplementation. Over two years, the patient showed improved growth velocity and reduced hypercalciuria, though nephrocalcinosis and renal cysts persisted. This case of WDR72-associated dRTA complicated by renal cyst formation is an underrecognized phenotype of this rare disorder. It further highlights that delayed diagnosis and prolonged, uncorrected tubulopathy may result in structural renal injury that is not fully reversible with treatment. Systematic renal evaluation, including biochemical assessment and renal ultrasonography, is strongly warranted in all children presenting with AI, particularly in the presence of concurrent growth failure, electrolyte disturbances, or rachitic changes, to facilitate early diagnosis and mitigate the risk of long-term renal sequelae.

Vallabhaneni P
Dawman L
Bhatia A
Kumar V
Bala A
Tiewsoh K

Humans
Male
Acidosis, Renal Tubular
Child
Phenotype
Kidney Diseases, Cystic
Nephrocalcinosis
Proteins
Hypokalemia
Exome Sequencing
Amelogenesis Imperfecta
Hypercalciuria
Hypophosphatemia


Immune-complex-mediated membranoproliferative glomerulonephritis with linear IgG staining resembling atypical anti-glomerular basement membrane disease: a case report

Abstract: Anti-glomerular basement membrane (anti-GBM) disease typically presents as rapidly progressive glomerulonephritis, however an atypical anti-GBM nephritis with various light microscopic findings without crescentic formation has been reported in recent years. The findings reported including cases with membranoproliferative glomerulonephritis (MPGN) pattern. Few reports have been able to follow the course of the disease over a long period of time. We report a case of MPGN associated with the spectrum of atypical anti-GBM nephritis that showed a slowly progressive course over more than eight years. A 49-year-old man underwent kidney biopsy because of hypertension, proteinuria, and mild renal insufficiency. The findings on kidney biopsy showed the findings of MPGN. Immunofluorescence microscopy revealed bright linear staining of IgG on the GBM. Electron microscopy showed subepithelial, intra-basement membrane, subendothelial, and paramesangial electron-dense deposits. Serum anti-GBM antibodies were negative. Proteinuria had been present for 4 years prior to the renal biopsy, however no worsening of renal function was observed. Because of worsening proteinuria and the presence of endocapillary hypercellularity in the tissues, the intravenous and oral steroids were started. Although the proteinuria showed slight improvement, the serum creatinine level was stable around 1.5-1.7 mg/dl. Although some indolent cases of atypical anti-GBM syndrome were reported previously, compared with these cases, our patient had more stable renal function for a long time. This is a rare case of resembling atypical anti-GBM disease that shows MPGN with linear IgG staining having a long-term indolent course and without secondary etiology.

Hisamichi-Yamamoto M
Ichikawa D
Ushimaru S
Shirai S
Koike J
Sakurada T
Shibagaki Y

Anti-Glomerular Basement Membrane Disease


[Microcephalic osteodysplastic primary dwarfism type II with hypergonadotropic hypogonadism in a 16-year-old patient]

Abstract: Microcephalic osteodysplastic primary dwarfism type II (MOPDII) is a form of primordial nanism characterized by extreme short stature, microcephaly, specific phenotype, maxillofacial dysmorphisms, skeletal dysplasia, disorders of carbohydrate metabolism, and neurovascular abnormalities. This article describes a patient with a Seckel syndrome phenotype presenting with left internal carotid artery aneurysms with intracerebral hemorrhages, thrombocytosis, arterial hypertension, and diabetes mellitus due to insulin resistance confirmed by a low Matsuda index. Target carbohydrate metabolism values were achieved on metformin therapy. Clinical exome sequencing revealed two rare heterozygous variants in the PCNT gene: c.6220C>T (p.Gln2074*) and c.4564-12T>A. Comparison of the results of the molecular genetic study and the patient's phenotype allowed us to verify the diagnosis of MOPDII. Hypergonadotropic hypogonadism was described for the first time in this syndrome.

Platonov VV
Noskova ED
Skorodok YL
Plotnikova EV
Suspitsin EN
Yakovleva TV
Tsoraeva FZ
Polanskaya MA
Jamiyeva SA

Humans
Microcephaly
Dwarfism
Hypogonadism
Osteochondrodysplasias
Adolescent
Male
Fetal Growth Retardation
Phenotype
Antigens

Journal Article
Case Reports
English Abstract


Semaglutide-Induced Sarcopenia via GLP-1R-mTOR-Satellite Cells Axis and Muscle-Glucose Feedback Loop Potentially Leading to Refractory Hyperglycemia in Type 2 Diabetes: A Case-Driven Hypothesis

Abstract: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) like semaglutide have transformed type 2 diabetes mellitus (T2DM) management, yet emerging concerns highlight potential risks of accelerated sarcopenia and subsequent metabolic disruptions. This case-driven hypothesis explores a 53-year-old male with T2DM diagnosed in 2014, who experienced progressive glycemic failure despite standard therapies, including metformin, glipizide, sitagliptin, and empagliflozin. Transition to dulaglutide 1.5 mg for 1.5 years followed by semaglutide (titrated from 0.25 to 1 mg weekly starting September 2024) resulted in weight loss from 84 kg to 70 kg by September 2025, accompanied by sarcopenic symptoms (muscle weakness, reduced mobility) and refractory hyperglycemia (fasting glucose 300 mg/dL, HbA1c 9%), persisting post-discontinuation on September 1, 2025, despite metformin and empagliflozin. We posit that semaglutide may precipitate acute sarcopenia via unexpected GLP-1R-mTOR-satellite cells axis crosstalk, disrupting AMPK-mTOR balance to suppress anabolic mTORC1/IGF-1 signaling (potentially by 25-35%) while enhancing catabolic FOXO/ubiquitin-proteasome and excessive autophagy pathways. This could extend to myokine reprogramming (elevated myostatin/GDF15, reduced irisin/IL-15), glucagon/α-cell compensation inducing hyperglucagonemia (15-25% rise), microbiome-bile acid shifts fostering low-grade inflammation (IL-6/TNF-α upregulation by 10-15%), mitochondrial mass reduction (20-25% via AMPK), and NMJ disassembly, collectively impairing muscle as the primary glucose sink (reducing GLUT4-mediated uptake by 35-45%) and initiating a «muscle-glucose feedback loop» with hepatic gluconeogenesis amplification, yielding treatment-resistant hyperglycemia.Supporting evidence from cohorts (e.g., 24-month study showing ASMI/grip strength declines in 432 patients), longitudinal analyses (NMJ degradation with CAF22/NfL elevations in 141 men), secondary trials (9.3% psoas volume loss in 51 MASLD cases), and case reports (fatigue in a 74-year-old, rhabdomyolysis in a 47-year-old) aligns with this framework, as does in vitro data linking GLP-1 excess to kinesin-1/GLUT4 inhibition and ATP depletion (20-30%). This novel hypothesis underscores sarcopenia's role in GLP-1RA-induced metabolic paradoxes, urging prospective studies on muscle-preserving interventions like resistance training or GLP-1R modulators to refine T2DM paradigms and inspire multidisciplinary research into endocrine-muscle interactions.

Semaglutide
Humans
Male
Diabetes Mellitus, Type 2
Middle Aged
Glucagon-Like Peptides
TOR Serine-Threonine Kinases
Sarcopenia
Hyperglycemia
Glucagon-Like Peptide-1 Receptor
Hypoglycemic Agents
Satellite Cells, Skeletal Muscle
Muscle, Skeletal
Glucose


Clinical Case Series of Destructive Thyrotoxicosis Associated with Hashimoto's Thyroiditis Misdiagnosed as Graves' Disease: Clinical Patterns, Diagnostic Pitfalls, and Hypothesized Molecular Insights

Abstract: This descriptive clinical case series analyzes five cases of destructive thyrotoxicosis associated with Hashimoto's thyroiditis, historically referred to as hashitoxicosis, initially misdiagnosed as Graves' disease, highlighting a persistent diagnostic challenge in autoimmune thyroid disorders. The series includes four published cases reported between 2000 and 2025 and one unpublished case contributed by the authors. The cohort comprised three females and two males, with a mean age of 55.4 years (range: 21-69). Clinical presentations were heterogeneous, most commonly fatigue (80%), palpitations (60%), and weight changes (40%), while two patients exhibited no overt hyperthyroid symptoms.Biochemical evaluation demonstrated suppressed thyroid-stimulating hormone (TSH) levels in all cases (range: <0.000-0.13 µIU/mL), elevated anti-thyroid peroxidase (anti-TPO) antibodies in 80% (range: 41->1,000 IU/mL), and initially negative thyroid-stimulating hormone receptor antibodies (TRAb/TSI) in 60% of patients. Seroconversion to positive TRAb/TSI was observed in two cases during follow-up, suggesting autoimmune overlap rather than definitive disease transition. Imaging findings, including thyroid ultrasonography and radioiodine uptake (RAI) studies, consistently favored destructive thyroiditis over stimulatory hyperthyroidism, with heterogeneous echotexture observed in 75% of assessed cases and low or normal RAI uptake in all evaluated patients.Misdiagnosis occurred in 80% of cases, predominantly due to reliance on suppressed TSH levels without TRAb confirmation, resulting in inappropriate antithyroid drug administration in 80% and accelerated hypothyroidism in 60%. Immunopathological interpretation based on existing literature supports a predominantly Th1-mediated destructive process, in contrast to the Th2-driven antibody-mediated stimulation characteristic of Graves' disease, with rare Th1-to-Th2 immune shifts reported. Clinical outcomes ranged from spontaneous resolution to surgical intervention.This case series underscores the importance of mandatory TRAb testing, adherence to American and European Thyroid Association guidelines, and early specialist referral to reduce iatrogenic harm and improve diagnostic precision in autoimmune thyroid disease.

Humans
Graves Disease
Female
Male
Hashimoto Disease
Adult
Middle Aged
Thyrotoxicosis
Aged
Diagnostic Errors
Autoantibodies
Thyrotropin
Young Adult


Interstitial Lung Disease in a Dental Technician Diagnosed Through an Integrated Multidisciplinary Approach

Abstract: Evidence from the literature indicates that workers in the dental care sector are routinely exposed to hazardous airborne agents, particularly mineral and metal dusts. This occupational risk is further amplified in settings with inadequate ventilation and insufficient use of personal protective equipment. We discuss the case of a dental technician with a significant history of occupational exposure who presented to our clinic with exertional dyspnea. High-resolution computed tomography revealed fibrosing nonspecific interstitial pneumonia associated with emphysema, and spirometry showed a severe reduction in carbon monoxide diffusion capacity. After a multidisciplinary evaluation, we performed bronchoscopy with bronchoalveolar lavage (BAL), which revealed an abundance of macrophages. Scanning electron microscopy with energy-dispersive spectrometry of the BAL detected silicon oxide, calcium, iron, and traces of metals typical of dental alloys (titanium, aluminum), as well as rare earth elements and toxic pollutants. These findings supported the diagnosis of interstitial lung disease due to long-term occupational exposure in dental laboratories, enabling a minimally invasive diagnostic approach. This strategy obviated the need for transbronchial biopsy, thereby avoiding a procedure associated with a high risk of pneumothorax in this patient.

Giulianelli G
Maggioni G
Daverio M
Polverosi R
Della Barbera M
Mason P
Spagnolo P
Basso C
Calabrese F
Rizzo S
Balestro E

Humans
Lung Diseases, Interstitial
Dental Technicians
Occupational Diseases
Occupational Exposure
Male
Patient Care Team
Bronchoscopy
Bronchoalveolar Lavage Fluid


Nontraumatic acute compartment syndrome in all four extremities secondary to myxedema coma

Abstract: Acute compartment syndrome (ACS) is a rare but potentially fatal sequela of myxedema coma. This article reports the second documented case of the presentation and management of a patient who developed ACS in all four extremities from severe hypothyroidism. This case represents an exceptional presentation of myxedema coma and highlights the potentially life-threatening complications from hypothyroidism and its improper treatment.

JAAPA : official journal of the American Academy of Physician Assistants

Humans
Myxedema
Coma
Hypothyroidism
Compartment Syndromes
Acute Disease
Male
Female


Acute Klebsiella pneumoniae infection of the knee joint following anterior cruciate ligament reconstruction in a young adult: A case report

Abstract: Acute postoperative infection caused by Klebsiella pneumoniae after anterior cruciate ligament reconstruction in young, immunocompetent individuals is exceedingly uncommon. An immunocompetent man in his early 20s developed fever and progressive swelling of the knee 5 days after anterior cruciate ligament reconstruction. Laboratory evaluation demonstrated markedly elevated inflammatory markers, including a C-reactive protein level of 18.36 mg/dL and synovial fluid white blood cell count of 62,667/mm3. Culture of aspirated synovial fluid confirmed infection with Klebsiella pneumoniae, establishing a diagnosis of acute postoperative septic arthritis of the knee. The patient underwent prompt arthroscopic debridement with biofilm debulking. Empirical intravenous piperacillin-tazobactam was administered for 3 days, followed by targeted intravenous levofloxacin for 5 days, and oral levofloxacin to complete an 8-week antimicrobial course. Infection was successfully controlled without graft or implant removal. The patient exhibited clinical improvement with resolution of fever and inflammatory signs following treatment. This case highlights that acute Klebsiella pneumoniae infection of the knee joint can occur even in young, immunocompetent patients shortly after anterior cruciate ligament reconstruction, without an identifiable remote infectious focus. Early recognition, prompt arthroscopic intervention, minimal implant burden, and appropriate targeted antibiotic therapy may enable successful infection control in selected patients.

The Journal of international medical research

Anterior Cruciate Ligament Reconstruction


Identification of a Duplication in the RP17 Locus in an Individual With Pathogenic CEP290 Variants: Implications for RP17 Variant Classification

Abstract: To assess the pathogenicity of a novel duplication in the RP17 locus identified in a cone dystrophy proband with biallelic CEP290 variants. Structural variants (SVs) in this locus have previously been associated with dominant retinitis pigmentosa. Inheritance of the duplication was assessed by breakpoint polymerase chain reaction (PCR). Ophthalmic evaluation included fundus examination, multimodal retinal imaging, and full-field electroretinogram (ERG). A proband-derived pluripotent stem cell line was differentiated into photoreceptor precursor cells (PPCs) and retinal organoids (ROs). Variant-induced mis-splicing of CEP290 was assessed by reverse-transcription PCR (RT-PCR) and long-read cDNA sequencing, and immunohistochemistry was used to assess photoreceptor morphology. Expression of GDPD1 was quantified by quantitative RT-PCR. The proband and father carried the 324-kb duplication in the RP17 locus. The father was clinically unaffected, but the proband showed features of cone dystrophy, including reduced visual acuity, foveal abnormalities, diminished cone density, and preserved dark-adapted but absent light-adapted ERG responses. The compound heterozygous variants in CEP290 resulted in pseudoexon inclusion and exon 36 skipping in patient-derived retinal cells. Immunohistochemistry revealed altered ciliation and reduced trafficking of L/M opsin and rhodopsin in ROs. In silico modeling predicted that the novel RP17 duplication does not disrupt chromatin looping, and GDPD1 expression was not upregulated in patient ROs, in contrast to pathogenic RP17-SVs. The cone dystrophy phenotype of the proband can be attributed to the CEP290 variants, whereas the novel RP17 duplication can be classified as likely benign based on the integrated evidence. These findings emphasize the importance of modeling and functional studies for accurately classifying RP17-SVs and preventing misinterpretation in clinical diagnostics.

Investigative ophthalmology & visual science

Holtes LK
Chen D
Guilfoyle S
O'Leary H
Corral-Serrano JC
Boonen EGM
Haer-Wigman L
Nieuwenhuis SE
Guarascio R
Toulis V
Andrade de Jesus D
Cremers FPM
Thiadens AAHJ
Cheetham ME
de Bruijn SE
Hardcastle AJ
Roosing S

Humans
Cell Cycle Proteins
Male
Electroretinography
Pedigree
Centrosomal Associated Proteins
Gene Duplication
Antigens, Neoplasm
Cone Dystrophy
Immunohistochemistry
Cytoskeletal Proteins
Retinitis Pigmentosa
Female
DNA Mutational Analysis


Delayed Onset of Acute Compartment Syndrome of Lower Leg and Foot after Crush Injury. Case Report

Abstract: <p>This case report presents a 25-year-old man who sustained a crush injury to the right lower limb at the workplace due to compression by a car wheel hub. Initial examination revealed marked swelling of the lower leg and midfoot with preserved sensation and peripheral perfusion. Radiographs demonstrated a bimalleolar ankle fracture and multiple foot fractures. Approximately 5 hours after admission, the patient developed rapidly increasing pain, pallor and cooling of the foot, absence of the dorsalis pedis pulse, decreased toe sensation, and oxygen saturation of 80%. CT angiography showed absent flow in the distal segments of the anterior tibial and fibular arteries. An urgent fasciotomy of the lower leg and dorsal foot compartments was performed ten hours after injury using the shoelace technique, resulting in immediate restoration of perfusion and foot warmth. Sixteen days later, necrotic tissue was debrided, the defect was covered with a split-thickness skin graft (Thiersch technique), and the medial malleolus was stabilized with Kirschner wires. Wound healing was uneventful, with no signs of infection. This case highlights the dynamic and potentially misleading course of acute compartment syndrome and underscores the need for frequent clinical reassessment despite an initially reassuring presentation. Prompt diagnosis and immediate complete fasciotomy prevented irreversible complications.</p&gt.

Majchrzak JJ
Rzyczniok P
Dugiełło B
Sobolewski J
Mazur D
Wawrzynek W
Stołtny T

Humans
Male
Adult
Crush Injuries
Compartment Syndromes
Fasciotomy
Foot Injuries
Treatment Outcome
Leg Injuries


Obstructive Hypertrophic Cardiomyopathy


Restless Legs Syndrome and Periodic Limb Movements

Abstract: This article describes the diagnostic criteria of restless legs syndrome (RLS) and periodic limb movements. The pathophysiology of RLS and its management are discussed. The approach to address RLS augmentation is also reviewed. In the 2025 American Academy of Sleep Medicine RLS treatment guidelines, long-term dopamine agonist therapy for RLS was downgraded because of the accumulating evidence of augmentation. In this context, it is important to optimally use IV iron therapy in patients with RLS. Ferric carboxymaltose is more likely to cause hypophosphatemia compared with other IV iron therapy formulations. Bilateral peroneal nerve stimulation demonstrated efficacy and safety, and it can be used as adjunct therapy in patients with refractory RLS. Data from the National RLS Opioid Registry demonstrated reassuring findings, reiterating the role of opioids in the treatment of patients with RLS. An increased periodic limb movement index can often be seen in patients with RLS. Dopamine agonists are no longer considered first-line pharmacologic therapy in patients with RLS. The mainstay of treatment is α2δ calcium channel ligands.

Humans
Restless Legs Syndrome
Nocturnal Myoclonus Syndrome
Female
Male
Dopamine Agonists
Middle Aged


Sleep Diagnostics and Monitoring Technology in Obstructive Sleep Apnea

Abstract: This article helps neurologists understand modern approaches to diagnosing obstructive sleep apnea, including the clinical role and limitations of home sleep apnea testing, and learn how they can integrate wearable and noncontact technologies into patient care to improve diagnostic efficiency, monitor treatment, and reduce health disparities. Advances in home sleep apnea testing have expanded beyond traditional type III monitors to include wearable devices such as wrist sensors and smart rings and noncontact "nearable" systems that use radar or acoustic signals. Since 2019, the US Food and Drug Administration (FDA) has cleared numerous software-as-a-medical-device platforms that leverage artificial intelligence and multisignal integration to estimate sleep parameters. These tools improve accessibility, particularly for patients who are unable or unwilling to undergo in-laboratory polysomnography. However, awareness of racial bias in pulse oximetry, regulatory gaps, variable accuracy, and privacy concerns highlight the need for further validation to ensure equitable and reliable clinical use. Obstructive sleep apnea is common and underdiagnosed, particularly in patients with neurologic conditions. In-laboratory polysomnography remains the gold standard for the diagnosis of obstructive sleep apnea but is limited by cost and access, whereas home sleep apnea testing offers a validated alternative for appropriate patients. Wearable and nearable technologies expand diagnostic options, improving usability and scalability, although their accuracy and validation vary. Neurologists play a key role in identifying patients at high risk, selecting the appropriate test, and interpreting results with awareness of limitations such as pulse oximetry bias. Consumer devices can raise awareness but should not replace clinical evaluation, and modern continuous positive airway pressure (CPAP) platforms enhance remote monitoring and management.

Humans
Sleep Apnea, Obstructive
Polysomnography
Wearable Electronic Devices
Female
Male
Remote Patient Monitoring
Digital Health
Monitoring, Physiologic


Sleep and Neurodegeneration

Abstract: This article discusses the relationship between sleep and neurodegenerative disorders. Sleep disorders disrupt neurotransmitters, facilitating the progression of neurodegenerative changes. Sleep impairment promotes amyloid-β aggregation, propagating memory impairment in neurodegenerative disorders. The use of biomarkers for early diagnosis of neurodegenerative disorders may include sleep features. Sleep apnea is associated with an increased risk of Parkinson disease. Sleep disorders, such as obstructive sleep apnea, are five times more likely in people with Alzheimer disease. Notably, individuals with genetic factors, including carriers of APOE4, are found to have decreased overall regulation of regions within the brain that control sleep. External factors that increase the risk of dementia include long-term use of antihistamines. The risk of mild cognitive impairment is reduced with the intake of 200 mg/d of caffeine, which aligns the circadian activity of suprachiasmatic nucleus cells. People diagnosed with idiopathic rapid eye movement (REM) sleep behavior disorders have more than a 90% risk of developing an α-synucleinopathy at 14 years follow-up.

Humans
Neurodegenerative Diseases
Sleep Wake Disorders
Sleep
Female
Male


Central Sleep Apnea

Abstract: Understanding respiratory control during sleep is fundamental to understanding the approach to the diagnosis and management of central sleep apnea (CSA). CSA is not one disease but rather a syndrome resulting from a heterogeneous group of etiologies. There are complex chemical, metabolic, mechanical, and neural contributions that can cause dysregulation in loop gain, decreased central respiratory drive, or both. The traditional dichotomy between obstructive versus central sleep apnea is overly simplistic. Conventional CSA is the extreme end along a continuum between obstructive and central phenotypes of sleep apnea. In addition to assessing CSA severity from sleep study data, new approaches, including computational analytics and the use of wearable technologies, are increasingly aimed at extrapolating additional information to characterize CSA etiology. Various positive airway pressure modalities are available to treat CSA, but residual disease is common. There is a better understanding of drugs as causes and as treatments of CSA. Phrenic nerve stimulation is a new treatment option. Multimodal therapy is the likely future of CSA therapy. CSA can be mechanistically divided into hypercapnic and hypocapnic CSA, with the six CSA syndromes in the International Classification of Sleep Disorders (Third Edition, Text Revision) falling under one or both of these categories depending on their etiology. Understanding the obstructive-central continuum of sleep apnea, in which the degree of contribution from each underlying sleep apnea driver, known as endotypes, predicts the relative central disease of a given patient on this continuum, can enhance comprehensive management.

Humans
Sleep Apnea, Central
Female
Male
Polysomnography
Continuous Positive Airway Pressure
Middle Aged


Obstructive Sleep Apnea

Abstract: Obstructive sleep apnea (OSA) is a common disorder that can have a significant negative impact on quality of life and health, including many neurologic disorders. This article discusses the updates in the diagnosis, implications, and treatment of OSA. New recommended criteria for diagnosing OSA increase the recognition of the disorder. Although the apnea-hypopnea index has been the metric used to diagnose, stratify severity, and monitor treatment, it has limitations. A growing number of other metrics, including hypoxic burden, sleep quality, arousal index, respiratory event duration, and daytime sleepiness, are important to consider for comprehensive assessment and risk stratification. Various endotypes and phenotypes of OSA may have certain risks and respond differently to treatment. Treatment of OSA may improve several neurologic symptoms and reduce the risk of neurologic comorbidities. Although positive airway pressure therapy remains the most efficacious treatment of OSA, several alternatives are available, and the list is rapidly expanding, including hypoglossal nerve stimulation and medications. Neurologists should screen for signs and symptoms of OSA as well as consider testing in patients at high risk who are asymptomatic. Treatment should be tailored based on the severity of OSA, objective data such as the arousal index and hypoxic burden, symptoms, comorbidities, and several patient factors, including morphologic characteristics and personal preferences. OSA is a treatable condition that, when well-managed, may lead to improvement of many neurologic conditions and quality of life.

Humans
Sleep Apnea, Obstructive
Female
Male
Polysomnography
Continuous Positive Airway Pressure
Middle Aged
Quality of Life


Hypersomnia

Abstract: The purpose of this article is to provide an overview of how to evaluate, diagnose, and manage patients with hypersomnia disorders. The extended-release formulation of sodium oxybate to treat narcolepsy with a dosage of once a night, rather than twice a night, was approved in 2023 for adults and in 2024 for pediatric patients aged 7 years and older by the US Food and Drug Administration (FDA). The novel pharmacokinetics of this formulation may improve medication adherence and reduce nighttime disruptions and sleep fragmentation for patients and their bed partners. Orexin receptor 2 agonists are also being investigated for the treatment of narcolepsy and idiopathic hypersomnia. CSF orexin testing can be used to diagnose narcolepsy type 1. Patients with hypersomnia have excessive daytime sleepiness, which can be due to an underlying sleep disorder or can be secondary to another condition. Diagnostic tools are useful but imperfect. It is essential to obtain a detailed sleep history to understand how patient symptoms are affecting daily life.

Humans
Disorders of Excessive Somnolence
Narcolepsy
Male
Child
Female
Adult


Insomnia

Abstract: This article reviews sleep basics, including stages, need, changes with aging, sleep drive, and circadian rhythm, to provide a normative framework and to reveal potential opportunities for insomnia intervention. In addition, it elucidates the symptoms, causes, consequences, diagnosis, and treatment of insomnia, including the role of sleep aids and cognitive behavioral therapy (CBT) for insomnia. The wide-ranging consequences of insomnia are increasingly appreciated, with research highlighting its detrimental effects on health. Newer medication options include three orexin receptor antagonists. Home-based sleep tracking may allow screening to identify contributing factors, including sleep disorders that require treatment, and assessment of the environment for early intervention to optimize sleep. Existing and emerging wearable technology and software as digital therapy will increase access to CBT for insomnia through increasingly individualized programs. Insomnia is the most common sleep disorder, with significant effects on quality of life and long-term health. Optimizing the sleep drive and circadian rhythm, addressing underlying causes, reducing hyperarousal, and enhancing conditioning are key components of improving the disorder. Over-the-counter and prescription sleep aids may have a limited role because of modest benefits and the potential for side effects. CBT for insomnia remains the preferred treatment, with a growing number of novel modes of access.

Sleep Initiation and Maintenance Disorders


Circadian Neurology

Abstract: Circadian rhythms describe the near 24-hour oscillations observed across almost all biological processes on Earth. These rhythms serve to coordinate our behavior and physiology with the 24-hour light-dark environment in which we live. This article highlights normal circadian physiology and the disorders that can develop when those processes are disrupted. Although historically circadian dysfunction has been viewed in terms of sleep-wake disorders, there is growing recognition that circadian disruption can contribute to or result from many other disorders frequently encountered within neurology. When caring for patients, it is important to recognize time as a variable in disease presentation and as a potential treatment that can be harnessed to optimize patient outcomes.

Humans
Circadian Rhythm
Chronobiology Disorders


Inpatient Sleep Medicine

Abstract: This article reviews the growing field of inpatient sleep medicine, addressing the importance of inpatient sleep quality and the evaluation and treatment of sleep disorders during and shortly after hospitalization. Sleep disruption and sleep disorders in the inpatient setting are associated with worse outcomes. Improving sleep quality and duration in the hospital and treating sleep disorders such as obstructive sleep apnea may improve in-hospital and short-term outcomes, such as mortality, stroke recurrence, and recovery. The 2025 American Academy of Sleep Medicine guidelines conditionally recommend the availability of inpatient sleep medicine services. Screening questionnaires can be used to prioritize objective testing for obstructive sleep apnea or empiric treatment in inpatients, but atypical symptoms in patients with stroke and congestive heart failure make them less sensitive. Objective screening tools such as high-resolution pulse oximetry may help prioritize resources but do not qualify patients for therapy such as CPAP; portable or in-laboratory sleep testing may be needed. Inpatient sleep medicine may be delivered by a multidisciplinary team based on available resources. Even if diagnosis or treatment cannot occur in the inpatient setting, recognizing sleep disorders during inpatient admissions increases the chances for successful outpatient treatment and can facilitate timely outpatient workup.

Humans
Sleep Wake Disorders
Inpatients
Female
Male
Sleep Medicine Specialty
Hospitalization
Sleep Apnea, Obstructive
Middle Aged
Sleep Quality


Sleep-Disordered Breathing in Patients With Neuromuscular Disorders

Abstract: Sleep-disordered breathing is a major contributor to morbidity and mortality in individuals with neuromuscular disorders, significantly affecting quality of life. This article provides a comprehensive review of respiratory physiology in the context of neuromuscular disorders, highlights essential components of a sleep-focused clinical history, and outlines evidence-based strategies for the diagnosis and management of sleep-disordered breathing as neuromuscular conditions progress over time. Sleep-disordered breathing testing can be accomplished in various settings to limit barriers to the identification of disease and treatment. Noninvasive ventilation technology has progressed to be more patient centric, with variable settings to ensure patient comfort and support. Early identification and treatment of sleep-disordered breathing in patients with neuromuscular disease can significantly improve quality of life and represent a readily modifiable factor in patient care. Noninvasive ventilation should be tailored to the individual patient's needs and comfort, with ongoing monitoring and adjustments based on specific neuromuscular diagnosis and disease progression.

Humans
Neuromuscular Diseases
Sleep Apnea Syndromes
Female
Male
Noninvasive Ventilation
Middle Aged


Sleep in the Developing Brain

Abstract: This article describes the variability of sleep needs throughout infancy and adolescence and the impact that primary or secondary changes in sleep architecture and sleep quality can have on children. It also reviews the changes in sleep as a child develops as well as the bidirectional relationship of sleep and pediatric neurodevelopmental disorders, epilepsy, and psychosocial health. Pediatric sleep has historically been understudied. Advances have made the quantitative study of pediatric sleep more feasible, although significant gaps remain. As early as prenatal life, sleep can affect a child's development, psychological health, and long-term sleep health. Genetic influences on circadian rhythm and brain development place many children at greater risk of sleep disorders and may one day be used to proactively screen for sleep disorders in children. Knowledge of common pediatric sleep disorders and the influence of sleep health on the impact of neurologic conditions is essential. Every child seen in a neurology clinic should be screened for sleep disorders, especially children with neurodevelopmental differences, epilepsy, or a history of structural brain abnormalities.

Humans
Brain
Sleep
Sleep Wake Disorders
Child
Female
Adolescent
Infant
Neurodevelopment
Male
Child, Preschool
Neurodevelopmental Disorders
Child Development


[Serological Characteristics and Transfusion of Passenger Lymphocyte Syndrome with Multiple Antibodies after Liver Transplantation]

Abstract: To explore the clinical features, serological test, and blood transfusion protocols of hemolytic anemia caused by passenger lymphocyte syndrome (PLS) with multiple antibodies after ABO-incompatible liver transplantation. The hemoglobin (Hb) and bilirubin levels were monitored in a patient (O blood type donor to B blood type) post-liver transplantation in our hospital. The ABO blood group typing, unexpected antibody screening and identify test, direct anti-globulin test (DAT) and acid elution test were performed respectively in blood samples of the patient to identify the serum and erythrocyte membrane sensitized antibodies. The patient's Hb showed a decreasing trend on the day 6 post-operation, reaching the lowest level of 37 g/L on day 12, while her serum bilirubin increased. The patient's ABO blood group did not match. The DAT and the irregular antibody screening test were positive. Anti-B, anti-E, anti-Jkb, and anti-Mur antibodies were detected in the serum, and the anti-B antibodies were detected in the elution liquid. After intermittent infusion of 9 U O type washed red blood cells after day 12, the Hb level increased steadily but the bilirubin level decreased gradually. The patient was discharged with improved conditions on day 38 after surgery. For patients undergoing ABO-incompatible liver transplantation, monitoring the Hb, blood type antibodies, and DAT is essential to timely diagnose PLS and adjust the treatment plan including transfusion strategy.

Wei YR
Huang HN
Wang YL
Huang HL
Wu CL
Liu FF
Li HL
He Y
Mo ZN

Humans
Liver Transplantation
Female
ABO Blood-Group System
Blood Group Incompatibility
Anemia, Hemolytic
Lymphocytes
Blood Transfusion
Syndrome


[Multidisciplinary Management and Diagnostic Insights for Refractory Postoperative Hemorrhage in Mild Hemophilia B Caused by Hemizygous F9 c.881G>A (p.Arg294Gln) Variant]

Abstract: To explore perioperative management strategies for mild hereditary hemorrhagic disorders and analyze multidisciplinary collaborative treatment protocols for refractory postoperative bleeding caused by F9 gene variants. We retrospectively reviewed the management of a 31-year-old male with persistent hemorrhage after mixed hemorrhoidectomy. Diagnostic data including coagulation tests ［activated partial thromboplastin time (APTT), coagulation factor activity］, genetic sequencing, and transfusion records was analyzed to summarize key lessons. The preoperative APTT was prolonged to 45.5 s (reference range: 22-38 s). Postoperative bleeding led to progressive hemoglobin decline (164→48 g/L), ultimately controlled with 10 U cryoprecipitate, 3 650 ml fresh frozen plasma (FFP), and 7.5 U red blood cells (RBC). Laboratory confirmation showed that factor IX (FIX) activity was 8.10%-10.10% (reference range: 60%-150%); un-corrected APTT mixing study; hemizygous pathogenic F9 c.881G>A (p.Arg294Gln) variant. Hemoglobin normalized to 121 g/L at 2-month follow-up, and no recurrence bleeding occurred. APTT prolongation serves as a critical warning sign for mild hemophilia B, mandating preoperative coagulation factor screening in males. The p.Arg294Gln substitution disrupts FⅨ catalytic activity, triggering refractory surgical hemorrhage. Multidisciplinary collaboration (replacement therapy+anemia correction) successfully managed life-threatening bleeding, early genetic diagnosis could prevent the risk of postoperative bleeding.

Humans
Male
Hemophilia B
Factor IX
Adult
Postoperative Hemorrhage
Retrospective Studies
Partial Thromboplastin Time


[Clinicopathological Characteristics of Follicular Lymphoma with a Predominantly Diffuse Growth Pattern]

Abstract: To investigate the clinicopathological features, diagnosis, differential diagnosis, treatment, and prognosis of a patient with follicular lymphoma with predominantly diffuse growth pattern (DFL), in order to enhance understanding of this rare lymphoma variant. Clinical and pathological data of one patient with DFL were collected. A retrospective analysis was conducted on the patient's clinical manifestations, pathological morphological features, immunophenotype, molecular genetic changes, treatment, and follow-up outcomes. Relevant literature was also reviewed. The patient was a 43-year-old female, presenting with a right inguinal area of more than four years' duration. Gross pathological examination revealed a single lymph node measuring 4.0 cm×3.0 cm×2.0 cm, with a gray-white, solid, and soft cut surface. Microscopic evaluation demonstrated architectural effacement and diffuse proliferation with focal residual indistinct follicular structures. Under high magnification, the tumor cells were predominantly centrocytes with a few scattered centroblasts in a heterogeneous background. Immunohistochemistry showed positive expression of CD10, BCL-6, and CD23 in tumor cells, but negative for BCL-2. STAT6 showed weak staining in <1% of tumor cells and was interpreted as negative. Fluorescence in situ hybridization (FISH) showed neither 1p36 deletion nor BCL2 rearrangement. Clonality analysis demonstrated clonal rearrangement of immunoglobulin genes, while T-cell receptor (TCR) gene rearrangement showed a polyclonal pattern. The patient underwent radiotherapy (24 Gy/12 fractions) to the right inguinal area, and has achieved complete remission to date. DFL is a rare subtype of follicular lymphoma with unique clinicopathological features and molecular genetic alterations, which may lead to diagnostic confusion with T-cell lymphomas. Accurate recognition of this subtype helps avoid misdiagnosis and inappropriate treatment. DFL is generally characterized by low histological grade, early clinical stage, and a favorable prognosis.

Humans
Lymphoma, Follicular
Female
Adult
Retrospective Studies
Prognosis


Suspected Denosumab-Associated Acute Coronary Syndrome

Abstract: Denosumab, a monoclonal antibody (mAb) targeting receptor activator of nuclear factor-κB ligand (RANKL), is commonly used in managing metabolic bone diseases and giant cell tumors (GCTs) of bone. Growing evidence suggests that RANKL inhibition may influence cardiovascular health by impacting endothelial function, inflammatory pathways, vascular smooth muscle cell behavior, and systemic calcium regulation. We report a case of a 48-year-old Caribbean-South Asian man with recurrent GCTs who received three subcutaneous doses of denosumab and soon thereafter developed an anterior ST-elevation acute coronary syndrome (STE-ACS). The patient had no traditional cardiometabolic risk factors. Coronary angiography revealed thrombotic occlusion of the proximal left anterior descending artery (LAD), which was successfully treated with primary percutaneous coronary intervention (PPCI) and guideline-directed medical therapy (GDMT). Given the lack of modifiable risk factors, a significant family history, and biologically plausible mechanisms linking RANKL inhibition to atherothrombotic events, a denosumab-associated myocardial infarction was considered the most probable cause.

Journal of investigative medicine high impact case reports

Maharaj M
Katwaroo A
Ramcharan P
Frederick JM
Seecheran V
Seecheran R
Teelucksingh J
Seecheran N

Humans
Denosumab
Middle Aged
Male
Acute Coronary Syndrome
Bone Density Conservation Agents
Coronary Angiography
Bone Neoplasms
Percutaneous Coronary Intervention
RANK Ligand


NRAS mutation in a central conducting lymphatic anomaly and PPFIBP1::ROS1 fusion in a Gorham-stout disease patient

Abstract: Lymphatic malformations (LMs) can lead to severe clinical complications, including disfigurement and even death. While genomic alterations have been identified in LMs, the genomic landscape of complex LMs remains poorly defined due to their rarity. In this study, we report two novel findings: an NRAS p.Q61R mutation in central conducting lymphatic anomaly (CCLA) and a PPFIBP1::ROS1 fusion in Gorham-Stout disease (GSD), both described for the first time in their respective LM subtypes. The discovery of the PPFIBP1::ROS1 fusion provided a unique opportunity to localize the somatic event to a specific cell type. Using serial tissue sections from the same specimen, we observed that the fusion signal was spatially associated with lymphatic endothelial cells, based on serial section analysis with D2-40 staining. Given that both NRAS mutations and PPFIBP1::ROS1 fusions have also been identified in other LM subtypes, our findings support the hypothesis that LMs may share common molecular mechanisms. We propose that phenotypic diversity among LM subtypes may arise from differences in developmental timing, anatomic location, and microenvironmental context at the time the somatic mutation occurs.

Yang G
Ren H
Wang J
Chen W
Li X
Chen S
Chen H
Zhao L
Fan W
Xiao S

Humans
Membrane Proteins
Mutation
GTP Phosphohydrolases
Osteolysis, Essential
Adaptor Proteins, Signal Transducing
Lymphatic Abnormalities
Oncogene Proteins, Fusion
Female


Fusobacterium necrophorum in necrotic laryngitis of feedlot cattle

Abstract: Necrotic laryngitis is an important cause of respiratory distress and economic loss in feedlot cattle. Describe the clinical presentation, pathologic lesions, and microbiologic findings associated with necrotic laryngitis in feedlot steers. Four 20-month-old feedlot steers diagnosed with necrotic laryngitis. Clinically affected steers exhibited inspiratory stridor, increased respiratory effort, and flared nares, indicative of upper airway obstruction. Samples from inflamed nasopharyngeal tissues were collected endoscopically using guarded cytology swabs and submitted for culture, with concurrent blood collection for CBC and plasma and serum biochemistry analyses. Endoscopic examinations identified laryngeal chondritis, mucopurulent diphtheritic membranes, and necrotic inflammation of the vocal folds. Aerobic cultures were negative, but anaerobic cultures yielded Fusobacterium necrophorum subsp. necrophorum and or F. necrophorum subsp. funduliforme. Hematologic evaluation indicated leukocytosis and increased plasma fibrinogen concentration, whereas serum biochemistry disclosed marked hyperglycemia and mild increases in hepatic enzyme activities, consistent with stress-related metabolic alterations. Antimicrobial susceptibility testing showed that F. necrophorum isolates were susceptible to β-lactams, tetracyclines, florfenicol, tiamulin, and trimethoprim/sulfamethoxazole, and resistant to aminoglycosides, fluoroquinolones, and with respect to macrolides, 4 strains were susceptible and 1 strain was resistant to tylosin, tilmicosin, and tulathromycin. These findings indicate involvement of either F. necrophorum subsp. necrophorum or subsp. funduliforme in necrotic laryngitis of feedlot cattle. Observed antimicrobial susceptibility patterns indicate ongoing susceptibility to β-lactams and tetracyclines, supporting their continued use as first-line therapeutic options.

Amachawadi RG
Miesner M
Beard W
Beard L
Thomson DU
Noffsinger T
Lukasiewicz K
Salih HM
Wang H
Nagaraja TG

Animals
Laryngitis
Fusobacterium necrophorum
Cattle Diseases
Cattle
Male
Fusobacterium Infections
Anti-Bacterial Agents
Necrosis
Microbial Sensitivity Tests


X-linked recessive ichthyosis with X-linked retinoschisis in two brothers: a case report

Abstract: X-linked ichthyosis (XLI) and X-linked retinoschisis (XLRS) are both inherited in an X-linked recessive manner. To date, no prior reports document both conditions' simultaneous occurrence. This case presents two brothers who were diagnosed with XLI combined with XLRS in a family. An 11-year-old boy (Case 1) presented to our hospital due to decreased bilateral vision detected during a physical examination over the past month. One month after birth, the parents noticed the child's skin was dry and rough. He was diagnosed with "ichthyosis" at another hospital, and after treatment, the condition improved. His mother had also been previously diagnosed with ichthyosis. The child was a full-term infant delivered by cesarean section, and his parents were not closely related. There was no family history of eye disease. Physical examination showed dry skin with diamond-shaped scales. The best-corrected visual acuity was 0.40 logMAR in both eyes. No abnormalities were observed in the anterior segments of both eyes. Fundus examination revealed petaloid macular edema, and OCT showed numerous cystic changes in the macular area of both eyes. His 6-year-old younger brother (Case 2) exhibited similar systemic and ocular features. Comprehensive ophthalmic and genetic examinations were performed on the entire family, revealing that both children carried an RS1 gene mutation, with the mutation site at c.545G>T/p.Arg182Leu, inherited from their mother. Additionally, a deletion variant of approximately 478 kb was found at the X chromosome p22.31 location, completely covering the STS gene region. Based on the genetic testing and ocular examination, both children were finally diagnosed with bilateral XLRS and XLI. This case expands the mutation spectrum of XLRS in Chinese patients and, for the first time, reports the ocular and systemic manifestations when two different disease genes, STS and RS1, coexist. The family members vividly demonstrate the phenotypic and genotypic individual heterogeneity associated with hereditary eye diseases. A comprehensive analysis of clinical phenotype and genotype improves clinical diagnosis and genetic testing accuracy, providing a clinical approach for a more comprehensive understanding of the disease.


Medical management of a traumatic rupture of the peroneus tertius tendon in a kid goat

Abstract: A 2-month-old Boer doeling weighing 13 kg that was intended for show and breeding was evaluated because of a 2-week history of right hind-limb lameness following suspected trauma sustained during an exhibition. Physical examination revealed a grade 4/5 lameness, stifle instability, and abnormal reciprocal apparatus function consistent with peroneus tertius (PT) rupture. Radiographs showed soft-tissue swelling without fracture. Ultrasonography identified synovial proliferation and a defect at the origin of the PT tendon compared with the contralateral limb. Synovial fluid analysis supported a traumatic inflammatory process. A diagnosis of PT tendon rupture with mild stifle sprain was made, and conservative management, including nonsteroidal anti-inflammatory therapy, antimicrobial administration, stall rest, and physical therapy, was initiated. The doeling was re-presented 2 wk later with worsening hind-limb lameness, new forelimb lameness, joint effusion, and respiratory abnormalities. Ultrasonography demonstrated abnormal joint effusion and diffuse pulmonary artifacts with mild pleural effusion. Arthrocentesis of the stifle and glenohumeral joints confirmed septic arthritis affecting multiple joints, suspected to be a result of hematogenous spread secondary to bronchopneumonia. Due to a poor prognosis for long-term soundness and productivity, euthanasia was elected. Key clinical message: This case documents an uncommon PT rupture in a goat and highlights the diagnostic value of ultrasonography, the risk of systemic disease complicating orthopedic injury, and the need for further characterization of prognosis and management of tendon injuries in small ruminants.

The Canadian veterinary journal = La revue veterinaire canadienne

Animals
Tendon Injuries
Rupture
Goats
Lameness, Animal
Goat Diseases
Anti-Inflammatory Agents, Non-Steroidal
Stifle
Female
Arthritis, Infectious
Anti-Bacterial Agents


Comparison of KAFO and AFO for extension thrust pattern after stroke: a randomized N-of-1 trial

Abstract: [Purpose] Extension thrust pattern (ETP) during the stance phase is a common gait deviation after stroke; however, there is no consensus regarding the optimal orthosis, such as knee-ankle-foot orthosis (KAFO) or ankle-foot orthosis (AFO). This study aimed to compare the effects of KAFO and AFO on ETP using an N-of-1 trial design. [Participant and Methods] A 54-year-old male with right thalamic hemorrhage and post-stroke hemiplegia participated in this study. A prospective multiple-crossover N-of-1 trial was conducted. Five intervention periods (3 consecutive days each) of KAFO and AFO use were randomly assigned, with a 1-day washout period between interventions. Hip, knee, and ankle joint angles during mid-stance, 10-m walking time, and step count were measured. [Results] KAFO use significantly reduced ankle plantar flexion compared with AFO. A particularly large effect size was observed for the ankle dorsiflexion angle. Improvements in walking time and step count were also noted with KAFO. [Conclusion] KAFO was more effective than AFO in improving ETP in this patient. Objective evaluation using an N-of-1 trial may support more appropriate orthotic selection in clinical practice.


Primary Klebsiella pneumoniae Ventriculitis Following Radiotherapy in a Patient with Nasopharyngeal Carcinoma: A Rare Case Report

Abstract: Ventriculitis is a severe central nervous system infection with high mortality. We present the case of a 24-year-old male with nasopharyngeal carcinoma who developed primary Klebsiella pneumoniae ventriculitis during hospitalization. He presented with fever, headache, and altered mental status. Due to acute hydrocephalus, an external ventricular drain was inserted, and subsequent cerebrospinal fluid (CSF) cultures yielded K. pneumoniae. Despite aggressive intravenous and intrathecal antibiotic therapy, the patient died from septic shock. This case highlights the rapid clinical deterioration associated with Gram-negative bacterial ventriculitis and the management difficulties encountered in immunosuppressed oncological patients, emphasizing the critical nature of this rare but fatal complication.

Infectious diseases & clinical microbiology

Kıymaz E
Çakır-Kıymaz Y
Yoldaş-Aslanoğlu ZP
Bulut Z


Ultrasound-Guided Percutaneous Fasciotomy of Three Compartments of the Leg for Chronic Exertional Compartment Syndrome in a High-Performance Contemporary Dancer: A Case Report

Abstract: Chronic exertional compartment syndrome (CECS) is a frequently underdiagnosed cause of exercise-induced leg pain that is activity-dependent. We present the case of a 20-year-old female, high-performance contemporary dancer with an approximately three-year history of progressive leg pain refractory to an exhaustive multimodal conservative treatment including NSAIDs, neuromodulators, physiotherapy with myofascial release, and botulinum toxin infiltration of three compartments. Complementary diagnostic studies including musculoskeletal Doppler ultrasound, magnetic resonance imaging (MRI), and electrodiagnostic studies yielded negative results, consistent with the dynamic nature of the condition. Based on the pathognomonic symptom pattern, imaging evolution, exclusion of neurological and vascular etiologies, and lack of results with conservative measures, a presumptive clinical diagnosis of multi-compartment CECS was established after exclusion of alternative diagnoses. In November 2025, the patient underwent ultrasound-guided percutaneous fasciotomy of the anterior, lateral, and superficial posterior compartments of the left leg via three minimally invasive incisions under regional anesthesia and sedation. Intraoperative reduction of compartmental tension was directly observed following each fascial release. A minor wound dehiscence resolved without further intervention. Serial visual analog scale (VAS) scores demonstrated progressive pain resolution (preoperative 9/10, three weeks 4/10, six weeks 3/10, three months 2/10, and six months 2/10), with a successful return-to-dance program protocol at final follow-up returning to old performance levels. This case highlights the diagnostic challenges of CECS in athletes, the limitations of conservative measures, and the technical feasibility of a simultaneous three-compartment ultrasound-guided percutaneous fasciotomy as a safe, effective, and minimally invasive solution.

Remolina Sánchez Rucobo E
Serrano-Ardila AM
Ponce de Leon Sandoval IA
Kerbel J
Apodaca Ramos GA
Ramos Rocandio NG
Castillo Vazquez FG


Non-Operative Management of a Failed Olecranon Fracture Fixation Leading to Functional Recovery: A Case Report

Abstract: An 85-year-old female walker dependent presented with a displaced olecranon fracture following a fall. Open reduction and internal fixation (ORIF) using an anatomic olecranon locking plate was performed. Two-week postoperative X-rays revealed fixation failure with persistent fragment displacement and a wide fracture gap. To manage this condition, non-operative management, including sling immobilization for 4 weeks and progressive physical therapy, was pursued with the elbow at 90 degrees flexion. At the 6-month follow-up, the elbow was pain-free with functional range of motion (ROM) being achieved, and functional independence was observed in daily activities including using a walker. This case highlights the potential for successful functional recovery through non-operative management in geriatric patients as an initial treatment or after a failed ORIF, emphasizing the importance of tailoring treatment to patient-specific factors and functional goals over radiographic outcomes.


The Silent Aneurysm Behind the Hoarse Voice: Ortner's Syndrome

Abstract: Unilateral recurrent laryngeal nerve palsy presenting with hoarseness of voice is a common clinical condition with multiple etiological factors, most commonly malignancy, iatrogenic injury, and neurological disorders. Cardiovascular causes are relatively uncommon and are described under Ortner's syndrome, also known as cardiovocal syndrome. Here, we describe the case of a 76-year-old gentleman who presented with progressively worsening hoarseness of voice and aspiration of fluids for two months. Video laryngoscopy revealed left vocal cord palsy and a phonatory gap. Contrast-enhanced computed tomography of the neck and chest demonstrated a saccular aneurysm of the distal aortic arch with mural thrombus compressing the course of the left recurrent laryngeal nerve. A diagnosis of Ortner's syndrome secondary to a saccular aortic arch aneurysm was made. This case highlights the need to consider Ortner's syndrome as a possible diagnosis in patients presenting with new-onset hoarseness of voice, particularly those with underlying cardiovascular disease.


Radiographic Documentation of Implant-Supported Rehabilitation Following Endodontic Failure of a Mandibular First Molar: A Case Report

Abstract: Endodontic failure is a common cause of tooth loss and frequently requires extraction when persistent infection and associated pathology compromise long-term prognosis. Dental implants provide a predictable treatment option for replacing missing teeth while restoring function and esthetics. This case report describes the radiographic documentation of implant-supported rehabilitation following endodontic failure of a mandibular first molar in a 44-year-old female patient. Initial radiographic evaluation revealed a previously endodontically treated mandibular right first molar (tooth #30) associated with persistent periapical pathology and an unfavorable prognosis. The tooth was extracted, and ridge preservation was performed using a bone graft material and a barrier membrane. After a three-month healing period, implant placement was completed with radiographic verification of implant position and proximity to adjacent structures using a guide pin. Following osseointegration, restorative procedures were initiated after implant uncovering through a digital workflow utilizing an intraoral scanner, scan body, and laboratory-fabricated screw-retained zirconia crown. Sequential radiographs documented the diagnostic, surgical, and restorative phases of treatment, including extraction site preservation, implant placement, healing, and definitive restoration. The final outcome demonstrated successful implant-supported rehabilitation with satisfactory radiographic positioning and restoration of function. This case highlights the value of radiographic assessment throughout implant therapy and illustrates a predictable treatment approach for replacing a mandibular first molar affected by endodontic failure.

Mejia Ocampo EM
Mora V
Romero M
Perez Quevedo M
De la Roche IC


Immune-Related Hepatotoxicity After Atezolizumab and Isoniazid

Abstract: Immune checkpoint inhibitor therapy has transformed the prognosis of multiple solid-organ malignancies; however, such advances are not without significant adverse events known as immune-related adverse events. A novel pattern of autoimmune-like hepatitis following exposure to certain medications, including statins, isoniazid, nitrofurantoin, anti-tumor necrosis factor-alpha therapy and minocycline, has recently been recognized. We present the case of a 66-year-old male patient with extensive-stage small-cell lung carcinoma who developed acute liver injury while receiving concomitant atezolizumab therapy and isoniazid prophylaxis for latent tuberculosis. The patient subsequently developed grade 4 hepatotoxicity, which improved after discontinuation of isoniazid therapy and initiation of corticosteroid treatment. The aim of this report is to contribute to the literature by presenting a rare case of grade 4 immune-related hepatotoxicity under atezolizumab therapy in a patient receiving isoniazid prophylaxis for latent tuberculosis.

Karakaya E
Çığ E
Saka B
Kağızmanlı H
Çöpür S
Gençdal G


Ischemic Stroke as a Possible Initial Manifestation of Primary Sjögren's Syndrome: A Case Report

Abstract: Primary Sjögren's syndrome (pSS), a chronic autoimmune disorder primarily affecting the exocrine glands, typically presents with sicca symptoms. Neurological involvement in pSS is uncommon as an initial presentation. Ischemic stroke, in particular, is a rare manifestation, while seizures are more commonly secondary to underlying structural or inflammatory central nervous system involvement. Here, we report a 41-year-old female who presented with a generalized tonic-clonic seizure preceded by left-sided tinnitus and associated with tongue biting, ocular deviation, and postictal confusion. Notably, seven years earlier, she had experienced a neurological event characterized by sudden-onset left-sided weakness and mouth deviation, with neuroimaging at that time reportedly demonstrating an acute infarction in the right temporoparieto-occipital region. During the current admission, brain imaging demonstrated chronic encephalomalacia and gliosis in the same region without evidence of acute infarction. Electroencephalography revealed focal epileptiform discharges in the left temporal lobe. Extensive evaluation of stroke etiologies was unrevealing. Subsequent immunological testing revealed positive anti-Sjögren's syndrome-related antigen A (SSA)/Ro and antinuclear antibodies (ANA). Although sicca symptoms were not reported at the time of the initial neurological presentation, the patient subsequently developed dry eye and dry mouth symptoms, prompting further evaluation with Schirmer's test and labial salivary gland biopsy, which confirmed the diagnosis of pSS. This case highlights the importance of considering autoimmune disorders, including pSS, in selected patients with cryptogenic neurological manifestations. It also underscores the diagnostic challenges posed by atypical presentations in the absence of classic sicca symptoms. Further studies are needed to better understand the relationship between pSS and cerebrovascular disease.


Functional Recovery Following Post-vaccination Neurological Syndrome With Demyelinating Findings on Magnetic Resonance Imaging (MRI): A Case Report

Abstract: Rare neurological syndromes have been reported following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, although a causal relationship remains uncertain. We report the case of a 62-year-old woman who developed progressive neurological impairment temporally associated with BNT162b2 (Pfizer-BioNTech) COVID-19 vaccination, resulting in wheelchair dependence. Brain magnetic resonance imaging (MRI) demonstrated multiple periventricular T2-weighted/fluid-attenuated inversion recovery (T2/FLAIR) hyperintense lesions, including lesions oriented perpendicular to the lateral ventricles, consistent with demyelinating features. A multimodal therapeutic approach was implemented, including gut-directed therapy, intravenous gold-induced cytokine (GOLDIC®) therapy, hyperbaric oxygen therapy (HBOT), intranasal exosome therapy, and structured neurorehabilitation. Over the course of treatment, the patient showed substantial clinical improvement, including recovery of ambulation and functional neurological status. While this case highlights the potential for significant neurological involvement following SARS-CoV-2 vaccination and the possibility of recovery with a multimodal therapeutic approach, the contribution of the individual therapies cannot be determined. Further research is needed to better understand the underlying mechanisms and to evaluate emerging therapeutic strategies, including GOLDIC, in this setting.


Clamshell Thoracosternotomy for Single-Stage Repair of a Rare Aortic Graft Infection Involving Ascending, Arch, and Descending Aortic Pathologies

Abstract: Single-stage repair of infected aortic grafts through a clamshell incision (bilateral thoracotomy with transverse sternotomy) is rarely undertaken, even when this approach could offer better exposure. We describe the use and considerations of a clamshell approach in the context of a rare prosthetic graft infection involving ascending, arch, and descending aortic segments. A 59-year-old man underwent aortic valve plus ascending aorta and total arch replacement for acute type A dissection. Eleven months later, he presented with a contained rupture at the distal anastomosis of his aortic arch graft. A thoracic endovascular aortic repair was performed extending into the descending aorta. However, within a few weeks, the patient developed fever and persistent distal anastomotic pseudoaneurysms, suggesting graft infection (without an obvious culprit organism). Replacement of the entire aortic arch, ascending, and descending aorta, preserving the aortic valve, was ultimately performed via a clamshell incision, requiring total circulatory arrest (eight minutes) and antegrade cerebral perfusion (28 minutes). Postoperatively, the patient was ventilated for 2.7 days and was discharged home on postoperative day 26 with empirical antibiotic therapy. The culprit organism was later identified as Parvimonas micra (P. micra) following extensive microbiological analysis (16S ribosomal deoxyribonucleic acid sequencing). The patient presented with hemoptysis and recurrent signs of infection on aortic imaging at approximately three months following his final operation. After discussion with the patient and family, nonoperative management was determined as the most appropriate path forward. This case illustrates the technical feasibility of this approach to address graft material present in the ascending, arch, and descending aorta. While the outcome was not ideal for this patient, our approach made this very extensive removal of graft material possible; such a procedure would not have been feasible with a midline sternotomy and would have required a multi-stage repair. Further, P. micra was an unexpected culprit, difficult to detect and detected late; this underscores the potentially growing importance of considering unexpected culprits and using advanced sequencing in culture-negative graft infections.

MacKinnon MJ
Ferguson DB
White CW
Cloutier J
Légaré JF


Unmasking cor triatriatum dexter in adult patients with atrial arrhythmia

Abstract: Cor triatriatum dexter is a rare congenital cardiac anomaly characterized by persistence of a membranous structure that divides the right atrium into two chambers. Although often asymptomatic, cor triatriatum dexter may present in adulthood with nonspecific symptoms and atrial arrhythmias, including atrial fibrillation and atrial flutter. We present a case series of four adult patients in whom cor triatriatum dexter was incidentally diagnosed during cardiac evaluation for diverse clinical presentations. Patients ranged in age from 51 to 75 years and presented with new-onset seizures, ischemic stroke evaluation, heart failure exacerbation, and recurrent atrial arrhythmias. In all cases, diagnosis was established using echocardiographic imaging, with transesophageal echocardiography providing definitive visualization when transthoracic studies were nondiagnostic. This series highlights the diagnostic challenges of cor triatriatum dexter in adults and suggests that the condition may be underrecognized. Furthermore, altered right atrial anatomy may be associated with atrial arrhythmia maintenance through structural and conduction alterations of the right atrium.

Almakadma AH
Inshyna D
Khan P
Sabra M
Ibrahim R
Farid M
Burkhanova U
Mehta D
Saeidifard F
Chadow HL


Nutritional management of feline chronic enteropathy with evolving dietary response and long-term stabilization

Abstract: A 5-year-old spayed female domestic shorthair cat was referred to the Clinical Nutrition Service at the Ontario Veterinary College (Guelph, Ontario) for management of chronic, nonresponsive enteropathy and recently diagnosed diabetes mellitus. The cat was presented with persistent diarrhea, perianal ulceration, weight loss, and poor glycemic control despite treatment with prednisolone, cobalamin injections, a hydrolyzed diet, and short antimicrobial trials. Once hospitalized, the cat was transitioned to a high-protein, low-carbohydrate commercial veterinary therapeutic diet containing mixed protein sources. Nutritional support was initiated via a nasogastric tube but discontinued after 48 h when voluntary oral intake resumed. Clinical signs improved gradually over 5 d, blood glucose stabilized below the renal threshold, and insulin therapy was discontinued at discharge after 6 d of hospitalization. The commercial veterinary therapeutic diet was maintained, and psyllium husk was later added to improve stool quality. Soft stools persisted for several months, with normalization occurring only after targeted fiber supplementation was introduced alongside ongoing medical management. This case highlights the importance of individualized nutritional management in chronic enteropathy, as clinical response to dietary intervention may evolve over time and long-term stabilization may require alternative strategies beyond hydrolyzed-protein diets. Key clinical message: Dietary responsiveness in feline chronic enteropathy is highly individualized. Hydrolyzed-protein diets are commonly recommended, but responses may vary between cases. Sequential and sustained dietary trials, guided by clinical response, may be necessary to achieve durable remission.

Fischer MM
Abood S
Collier A
Verbrugghe A

Animals
Cats
Female
Cat Diseases
Chronic Disease
Animal Feed
Intestinal Diseases
Psyllium


Chronic Lymphocytic Leukaemia (CLL)-Associated Proliferative Glomerulonephritis With Monoclonal Immunoglobulin Deposits (PGNMID) Diagnosed in the Absence of Detectable Paraprotein

Abstract: Renal involvement in chronic lymphocytic leukaemia (CLL) is uncommon but clinically relevant. We report a man in his early 70s with known CLL who presented with non-nephrotic proteinuria, progressive kidney injury, and hyperkalaemia. Kidney biopsy revealed diffuse membranoproliferative glomerulonephritis with IgG kappa monoclonal deposits on immunofluorescence and electron microscopy, establishing a diagnosis of CLL-associated proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID). Treatment with rituximab and chlorambucil resulted in significant improvement of both kidney function and proteinuria. This case highlights the pivotal role of kidney biopsy in CLL-associated nephropathy: it established a precise diagnosis in the absence of detectable circulating paraprotein, triggered clone-directed therapy, and demonstrated that meaningful renal recovery is achievable even in the context of acute kidney injury.

Rodrigues F
Pais M
Terencio R
Manso R
Silva J


Concomitant effect of high altitude and thrombophilia on multi-organ thrombosis

Abstract: We report the case of a 33-year-old male mountaineer, presenting with chest pain, severe headache, dyspnea, and lower extremity edema, on his first expedition to Paraw mountain located in Kermanshah Province. His condition involved a complex thrombotic presentation, including both venous and arterial events, such as a myocardial infarction due to stenosis of the left main coronary artery, which we believe to be a coincidental pathology. His neurological symptom includes headache, vomiting, and slight drowsiness associated with chest pain, which were evaluated alongside confirmatory testing for protein C-S deficiency. Physical examination revealed right lower extremity edema, respiratory distress (RR = 34), and mid-drowsiness. Chest X ray showed lung congestion. A history of recurrent thrombophlebitis, along with the current myocardial infarction, raised suspicion of a thrombophilic state. The final diagnosis of these complications was confirmed to have protein C-S deficiency based on laboratory tests performed during the acute phase. However, the hereditary nature of this deficiency remains unconfirmed as no genetic testing or family screening was undertaken. The patient underwent coronary artery bypass grafting of left anterior descending artery (LAD) and LCX associated with anticoagulant therapy, and his neurologic sign and symptom and lower extremity deep vein thrombosis recovered uneventfully.

Sabzi F
Faraji R
Shokri F
Ghaysouri A
Maleki A
Rashidi T


Effective "Pop-Out" Nucleus Technique in Cataract Surgery With Pseudoexfoliation: A Case Report

Abstract: Pseudoexfoliation syndrome (PXF) presents significant challenges in cataract surgery due to zonular weakness and poor pupillary dilation. We report a case of a 72-year-old woman with PXF who underwent cataract surgery using a "pop-out" nucleus technique facilitated by hydrodissection. The technique allowed the safe prolapse of the nucleus into the anterior chamber despite zonular instability. Postoperative visual outcomes were favorable, improving from 0.1 preoperatively to 0.9 one week after surgery. This case highlights the safety and effectiveness of the "pop-out" technique in managing complex cataract cases associated with pseudoexfoliation.


Spontaneous Splenic Rupture Associated With Cytomegalovirus Infection: A Case Report

Abstract: Atraumatic splenic rupture is a rare but potentially life-threatening condition, most commonly associated with infectious, hematological, neoplastic, inflammatory, or iatrogenic disorders. Cytomegalovirus (CMV)-associated splenic rupture is an exceptionally uncommon complication in immunocompetent individuals. We report the case of a 46-year-old immunocompetent man who presented to the emergency department with acute abdominal pain and a low-grade fever. Laboratory investigations revealed mild microcytic anemia, thrombocytopenia, elevated inflammatory markers, and mild transaminase elevation. Contrast-enhanced abdominal computed tomography demonstrated splenomegaly, a large perisplenic collection consistent with a subcapsular hematoma, and moderate hemoperitoneum, raising suspicion of atraumatic splenic rupture. During clinical observation, the patient developed hemodynamic instability, prompting emergency exploratory laparotomy. Intraoperative findings included massive hemoperitoneum, capsular laceration involving the upper pole, and an extensive subcapsular hematoma. Splenectomy was performed. Postoperative serological investigations revealed markedly elevated anti-CMV IgM levels associated with low anti-CMV IgG levels and low IgG avidity, consistent with acute CMV infection. The pathological examination supported the diagnosis of CMV-associated atraumatic splenic rupture. No antiviral therapy was deemed necessary following infectious disease consultation, and the patient recovered uneventfully with planned post-splenectomy vaccination. CMV infection has increasingly been linked to thrombotic and vascular complications, even in immunocompetent individuals. Proposed mechanisms of splenic rupture include endothelial dysfunction, transient prothrombotic states, lymphocytic infiltration of splenic tissue, ischemic injury, and reduced capsular elasticity. Since clinical manifestations are often nonspecific and may mimic other causes of acute abdomen, diagnosis can be challenging. Contrast-enhanced computed tomography remains the gold standard for diagnosis and therapeutic planning. Management depends on the severity of splenic injury and the patient's hemodynamic status; however, splenectomy remains the preferred treatment in cases of severe injury or hemodynamic deterioration. This case highlights the importance of considering CMV infection in the differential diagnosis of atraumatic splenic rupture and underscores the value of early imaging and prompt intervention in optimizing patient outcomes.