Citations

We present the case of a 12-year-old female who presented with progressive back pain and was found to have a localized mass in the lumbar spine. The resected tissue was characterized by epithelioid cells with a papillary appearance and high mitotic activity. Initial immunohistochemical analysis was consistent with a diagnosis of atypical meningioma. However, comprehensive molecular profiling detected a CRTC1::NCOA2 fusion with a novel NCOA2 gene rearrangement, leading to a revised descriptive diagnosis of epithelioid mesenchymal neoplasm with CRTC1::NCOA2 fusion. This specific fusion has only been reported in 2 other cases involving mesenchymal neoplasms of the palate and urinary bladder. While CRTC1 is frequently associated with MAML2 fusion in mucoepidermoid carcinomas, NCOA2 rearrangements occur in a variety of solid and hematologic malignancies. There is a paucity of information on the prognostic relevance of these fusion partners. This is the first reported case of a CRTC1::NCOA2 fusion in a pediatric patient with a spinal cord malignancy. The mechanistic significance and prognostic implications of this fusion will be discussed.

ABSTRACT Background Sodium–glucose co-transporter 2 inhibitors (SGLT2is) are emerging as an essential part of the standard of care for proteinuria in patients with chronic kidney disease. To date, no study has specifically evaluated the effects of body mass index (BMI) on the antiproteinuric efficacy of SGLT2is. Here we report the impact of BMI on the antiproteinuric efficacy of SGLT2is in non-diabetic patients with glomerular diseases. Methods This is a retrospective, multicentre, international observational cohort study that included non-diabetic patients with biopsy-proven glomerular disease and proteinuria >0.5 g/24 h who received SGLT2is between 2016 and 2023. Laboratory values, including proteinuria and estimated glomerular filtration rate (eGFR), were obtained at baseline and after 3–6 months. Changes in laboratory values over time were analysed using the paired signed-rank test. Results A total of 300 patients met the inclusion criteria. The median age was 51.82 years [interquartile range (IQR) 41–62.65], 64.7% were male and 92.7% were white. The most common glomerular disease was immunoglobulin A nephropathy (40.3%). The median eGFR was 52.26 ml/min/1.73 m2 (IQR 36.41–74.01), the median proteinuria was 1.60 g/24 h (IQR 1.15–2.91) and the median serum albumin was 4.08 g/dl (IQR 3.80–4.30). Proteinuria reduction after SGLT2i initiation was significant only in overweight and obese patients (P < .001 versus 0.18). Patients with normal BMI did not experience the expected early decrease in eGFR (P = .16). Conclusions SGLT2is are ineffective in proteinuria reduction in patients with a BMI <25 kg/m2, which contrasts with the significant proteinuria reduction in overweight and obese patients with glomerulopathies.

Hashimoto encephalopathy or steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) is a rare condition associated with rapidly progressive dementia, stroke-like symptoms, psychosis and positive antithyroid antibodies. In this case report, a woman in her 80s with hypothyroidism and no other medically relevant history presented with a 2-week complaint of progressive hallucinations, short-term memory loss and paranoia. Eventually hospitalised, her hospital course was complicated by severe hospital-acquired delirium, which clouded the clinical picture; however, initial workup revealed an elevated thyroglobulin antibody and thyroid peroxidase, both highly specific for SREAT. A 3-day course of high-dose methylprednisolone (1 g/day) was administered, which revealed marked improvement in patient symptoms. Definitive treatment included a 13-week oral prednisone taper and outpatient follow-up with neurology and primary care. In cases of new onset neuropsychiatric symptoms in geriatric populations, SREAT is a reversible, must-not-miss diagnosis, when treated with systemic steroids.

Introduction Male circumcision (MC) has been shown to decrease transmission of HIV and is a critical strategy to decrease its incidence in countries with high rates of heterosexually transmitted HIV. Early infant MC (EIMC), with single-use MC devices, could increase rates of MC in Sub-Saharan Africa. Our objective was to determine the safety, efficacy and satisfaction of ShangRing EIMC in resource-constrained environments. Methods Healthy male infants aged 1–60 days underwent ShangRing EIMC performed by non-physician clinicians in 14 sites in Kenya, Tanzania and Uganda. The primary outcomes were the safety and efficacy of ShangRing EIMC. Secondary outcomes were pain related to the procedure, wound healing and parental satisfaction. Male infants were assessed at discharge and on postoperative days 7 and 28 for wound healing and complications. This trial is registered with Clinical.Trials.gov, NCT03338699 , and is complete. Results From the 1697 participants enrolled from February to November 2020, 1691 (99.6%) underwent ShangRing EIMC. Median duration of the procedure was 10 min (IQR 6–13). The mean Neonatal Infant Pain Scale 20 min postprocedure was 0.3 (SD 0.8), indicating no pain. At the time of discharge, 1679 (99.0%) participants had a normal-appearing wound and 1574 (93.1%) demonstrated complete wound healing at 28 days. A total of 17 (1.0%) AEs were reported, most related to bleeding. A total of 1635 (99.1%) of parents were satisfied with the appearance of the circumcised penis at 28 days. Conclusion ShangRing EIMC is a simple and successful MC method that non-physician clinicians can perform safely, with low AE rate, satisfactory wound healing and high satisfaction rate among parents. This indicates that the ShangRing EIMC can be considered a long-term strategic approach to accelerate the scale-up of MC in Sub-Saharan Africa. Trial registration number NCT03338699 .

Background/Objectives: Pediatric heart failure (HF) is a complex clinical syndrome with diverse etiologies and presentations. Primary care providers (PCPs) are critical in early recognition, family education, and coordination of ongoing care in collaboration with pediatric cardiologists. This review provides a comprehensive guide for PCPs to understand the causes, symptoms, treatments, and longitudinal considerations for children with HF. Methods: We conducted a narrative review synthesizing published evidence and expert consensus guidelines, focusing on the clinical presentation, treatment options, and longitudinal care strategies in children with HF. Results: HF in children most commonly results from congenital heart disease and cardiomyopathy, but includes a wide range of etiologies. Presenting symptoms differ by age, with subtle signs often mistaken for common pediatric illnesses. Treatments range from disease-modifying medications to surgical and transplant therapies. Psychosocial support, mental health, and family-centered care are critical components of long-term management. Conclusions: PCPs are essential partners in the care of children with HF. A proactive, collaborative, and informed approach can improve quality of life, reduce hospitalizations, and support families navigating this challenging diagnosis.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease marked by cholestasis and progressive fibrosis. While ursodeoxycholic acid (UDCA) remains the first-line therapy, approximately 30–40% of patients have an inadequate biochemical response, increasing the risk of disease progression. Obeticholic acid (OCA), a potent farnesoid X receptor (FXR) agonist, was the first second-line agent approved by the only Food and Drug Administration (FDA) and has demonstrated moderate biochemical efficacy but limited tolerability due to dose-dependent pruritus and safety concerns in cirrhosis. Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPAR-α) agonist, showed substantial alkaline phosphatase (ALP) reductions when added to UDCA, although its long-term benefit remains unconfirmed in large-scale trials and its use remains off-label in the United States, unlike FDA-approved agents. Seladelpar, a selective peroxisome proliferator-activated receptor delta (PPAR-δ) agonist, and elafibranor, a dual PPAR-α/δ agonist, have both recently received FDA accelerated approval after demonstrating significant improvements in ALP, biochemical response rates, and pruritus relief in phase 3 trials. This review summarizes these second-line therapies’ mechanisms, efficacy, safety, and limitations emphasizing the need for individualized treatment decisions and ongoing research into long-term clinical outcomes.

ABSTRACTBackgroundPrimary progressive apraxia of speech is a neurodegenerative disorder characterized by early, isolated speech impairment due to impairment of motor speech planning and programming. Patients with PPAOS have varying disease durations from the estimated onset of the first symptom to death. Clinicopathological and neuroimaging features related to disease duration are unknown for PPAOS. We determine whether clinical, neuroimaging, or pathological features are associated with disease duration in primary progressive apraxia of speech (PPAOS).MethodsWe analyzed data from 41 PPAOS participants who were enrolled and longitudinally followed to death in NIH‐funded studies over 15 years. Demographic, clinical, and genetic features were abstracted. Brain volumes of cortical, subcortical, and brainstem regions were calculated. Regional tau lesion count (burden) was assessed histologically. Spearman rank correlations were performed between disease duration and variables of interest, followed by multiple regression analyses.ResultsDisease duration did not correlate with any baseline demographic, clinical, or pathologic features. Shorter disease duration correlated with a faster rate of behavioral change and of apraxia of speech severity over time, smaller baseline volumes of the superior frontal lobe and supplementary motor cortex, and higher tau burden in the locus ceruleus (ρ = −0.5, p = 0.03). Multiple regression analysis identified rate of behavioral change and volume loss in the superior frontal lobe as key clinical and neuroimaging variables, respectively.ConclusionIn patients with PPAOS, we found shorter disease duration to be related to behavioral dyscontrol and involvement of the frontal lobe, as well as a higher burden of 4‐repeat tau lesions in the locus ceruleus.