Citations

Abstract Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder infrequently complicated by delayed-onset pituitary disease. A 41-year-old female presented with papular, acneiform skin lesions. Shave biopsy demonstrated a superficial dermal epithelioid cell proliferation with S100, CD1a, and langerin positivity on immunohistochemistry and a BRAF p.N486_P490del inframe deletion-gain of function pathogenic variant on next-generation sequencing. The skin lesions spontaneously resolved. One year later, she developed progressive fatigue, fevers, anorexia, menstrual irregularities, polyuria, and polydipsia. Laboratory workup was consistent with panhypopituitarism. Pituitary magnetic resonance imaging noted mass-like thickening and enhancement of the infundibulum extending toward the hypothalamus. After treatment with cobimetinib, magnetic resonance imaging findings resolved but endocrinopathies persisted, requiring indefinite hormone therapy. This case demonstrates the full spectrum of endocrinopathies of LCH-induced pituitary disease and is an unusual circumstance of LCH with delayed-onset panhypopituitarism.

ABSTRACT Background Membranous nephropathy (MN) associated with phospholipase A2 receptor (PLA2R) antibodies is the most common cause of nephrotic syndrome in non-diabetic adult patients. This study investigated the relationship between clinical phenotypes and renal outcomes in this population, emphasizing the potential for phenotype-based treatment stratification. Methods We conducted a retrospective, multi-center cohort study of PLA2R-positive MN. Unsupervised cluster analysis grouped patients based on clinicopathological characteristics. Primary outcomes included complete or partial remission within 2 years of biopsy and end-stage kidney disease (ESKD) or death during follow-up. Results Among 178 patients, three distinct clusters emerged (n = 89, 70, and 19). Within 2 years of biopsy, 102 patients (57%) achieved complete or partial remission. Cluster 1, characterized by the mildest disease markers, including the lowest body mass index, serum anti-PLA2R titer, serum creatinine, proteinuria, and triglycerides, had the highest remission rate of 72%, compared with 50% in cluster 2 and 54% in cluster 3. Cluster 2 had significantly lower remission compared to cluster 1 (HR 0.64, 95% CI 0.42–0.96, P = .03); results were similar in cluster 3, albeit not statistically significant (HR 0.50, 95% CI 0.23–1.09, P = .08). Elevated anti-PLA2R levels (>100 U/ml) and proteinuria (>8 g/24-hour) predicted reduced remission (HR 0.56, 95% CI 0.36–0.88, P = .01; HR 0.43, 95% CI 0.26–0.73, P = .002, respectively), while high high-density lipoprotein levels were protective (HR 1.01, 95% CI 1.00–1.02, P = .048). Overall, 21 patients (12%) developed ESKD or died. ESKD-free survival differed significantly across clusters (log-rank test P = .04). Conclusions Unsupervised clustering identified distinct clinical phenotypes in PLA2R-positive MN, each associated with different renal prognoses. Phenotype-based risk stratification could enhance treatment precision, improve patient outcomes, and potentially reduce treatment-related adverse effects.

Abstract Context Endothelial dysfunction and altered psychological measures have been identified in women with functional hypothalamic amenorrhea (FHA). Estradiol (E2) replacement, a known vasodilator, may potentially reverse vascular dysfunction and improve psychological health. Objective To evaluate 12 weeks of physiologic E2 replacement on vascular, hormonal, and psychological outcomes in women with FHA. Methods A randomized, double-blind, placebo-controlled trial was conducted in 29 women with FHA with 0.1 mg/day transdermal E2 (n = 14) or placebo patch (n = 15) twice weekly for 12 weeks. FHA was defined as amenorrhea ≥3 consecutive months, E2 < 50 pg/mL, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) <10 mIU/L, LH:FSH <1, excluding other etiologies. Endothelial dysfunction (reactive hyperemic index ≤ 1.67) was assessed, as were hormonal and psychological measures. Results Women with FHA had a mean age of 26.2 ± 6.3 years, body mass index of 21.5 ± 3.3 kg/m2, with 63% being non-Hispanic White. Baseline characteristics did not differ between groups. After 12 weeks, E2 levels were significantly higher in the E2 group (112.0 vs 36.5 pg/mL, P = .0002). However, there were no significant differences in vascular, hormonal, or psychological outcomes between E2 and placebo groups at week 12. Cortisol levels showed a near-significant decrease in the E2 group compared to an increase with placebo (−.4 vs 3.1 µg/dL, P = .05). Conclusion In women with FHA, 12 weeks of transdermal E2 increased serum E2 levels but did not improve vascular or psychological health measures. Further studies with larger sample sizes and longer follow-up are needed to explore the long-term effects of E2 therapy on cardiovascular and mental health outcomes in this population.

ABSTRACTBackgroundPancreatic cysts are increasingly discovered on imaging studies performed for unrelated conditions. Currently, surveillance of these lesions poses a substantial burden on patients, and health care recourses. We hypothesized that individuals with small and stable cysts have a diminutive risk of progressing to high‐grade dysplasia (HGD) or pancreatic cancer (PC) that is similar to that in the general population.MethodsThis nested PACYFIC‐study is a collaboration among 44 centers in Europe and Northern‐America, and investigates the risk of HGD and PC for different cyst sizes and growth rates in participants without baseline worrisome features (WF) or high‐risk stigmata (HRS).ResultsOf the 2369 PACYFIC participants, 975 met the inclusion criteria, with a mean age of 67 years (SD 13) and 65% being female. Of these, 438 individuals (45%) had a baseline small cyst size (< 15 mm), and 885 (91%) individuals had a slow growth rate (< 2.5 mm/year). During a median follow‐up of 45 months (IQR 27), 20 individuals (2.1%) developed HGD, or PC. Individuals with small cysts had a 1.5‐fold lower risk of developing WF or HRS (hazard ratio [HR] 0.7 [0.5–1.0], p = 0.03) than those with larger cysts but a similar risk of developing HGD or PC (p > 0.05). Slow growth was protective against the development of WF or HRS (HR 0.4 [0.2–0.6], p < 0.001) and HGD or PC (HR 0.04 [95% CI 0.02–0.12], p < 0.001). Individuals with small, stable sized cysts without baseline WF or HRS did not have a higher risk of HGD or PC than the general population (standardized incidence ratio [SIR] 1.13 [95% CI 0.01–6.30]).ConclusionCyst size < 15 mm and growth rate < 2.5 mm/year appear to be “reassuring” features associated with a negligible risk of developing WF or HRS and HGD or PC. For cysts with these characteristics—and without baseline WF or HRS—less intensive surveillance (than currently recommended) or even cessation may be appropriate.

Flexible intramedullary nail fixation of pediatric femoral shaft fractures offers advantages such as shorter hospital stays, faster return to function, and less associated costs when compared with traction and casting. This study compared the biomechanical performance of three configurations: 2CS, 2CL, and 3CL. Thirty synthetic femur models with identical, length-unstable, spiral fractures were tested using a three-dimensional camera system to assess real-time micromotion. Three groups were analyzed: (a) 2CS – two 3.5 mm C- and S-shaped nails inserted anterograde, (b) 2CL – one ‘C’ and one ‘S’ shaped 3.5 mm titanium nail-inserted retrograde from a single lateral entry, (c) 3CL – two ‘C’ shaped 3.5 mm titanium nails inserted medially and laterally with a third ‘C’ shaped 2.5 mm nail placed retrograde from an anterolateral site. Torsional loading, cyclical loading, and load-to-failure tests were conducted. The 3CL configuration demonstrated superior biomechanical performance. It exhibited the highest torsional stiffness [0.67 ± 0.06 Nm/° for external rotation (ER), 0.404 = ± 0.06 Nm/° for internal rotation (IR); P = 0.002], least displacement (0.05 ± 0.02 vs. 0.30 ± 0.02 mm for 2CL and 0.57 ± 0.05 mm for 2CS; P = 0.012), and required the highest load-to-failure (162 ± 83 vs. 1064 ± 75 N for 2CL and 790 ± 34 N for 2CS; P = 0.016).The 3CL configuration provided superior strength and stability across all tests, supporting its role in the fixation of length-unstable pediatric femoral fractures.

Objective Motor neuron disease (MND) is a progressive neurological disorder with no known cure that damages motor neurons. The purpose of this analysis is to examine the place of death for MND patients in the United States during the coronavirus disease 2019 (COVID-19) pandemic and to investigate the extent of specific comorbidities. Methods We obtained death certificate and associated comorbidities data for all U.S. MND deaths from 2018 to 2021 and conducted a population-based cross-sectional analysis of the deaths pre-COVID-19 (2018-2019) and during COVID-19 (2020-2021). We hypothesized that place of death and comorbidities associated with place of death for MND patients in the United States were altered during the COVID-19 pandemic in comparison to the 2 years period before the pandemic. Results We analyzed 30 066 MND deaths (14 562 pre-COVID-19 and 15 504 during COVID-19) aged 20 years and older. During COVID-19, MND deaths at home increased (54.4% vs 45.5% pre-COVID). Hispanic individuals had an increased likelihood of dying at home compared to a nursing home or hospice (OR = 1.57, 95%CI: 1.22-2.02), but a decreased likelihood compared to a hospital (OR = 0.61, 95% CI: 0.51-0.72). Among the top comorbidities listed, there was a 27.8% increase in diabetes mellitus and a 20.2% increase in essential hypertension during COVID-19. During COVID-19, diabetes mellitus was more commonly reported as a comorbidity for deaths occurring in hospitals (OR = 1.40, 95%CI: 1.03-1.89) or at home (OR = 1.26, 95%CI: 1.03-1.55), while essential hypertension was more commonly reported with deaths at home (OR = 1.17, 95%CI: 1.01-1.36). Conclusion Our analysis showed an increase in at-home MND deaths as well as certain comorbidities during the COVID-19 pandemic, suggesting MND patients had a higher likelihood of death from non-COVID-19 comorbidities.

Cerebrospinal fluid venous fistulas (CSFVF) can lead to spontaneous intracranial hypotension, causing debilitating symptoms in patients. The transvenous embolization technique has been developed to occlude leakage sites via an endovascular approach. However, the spinal venous anatomy remains relatively unfamiliar to many neurointerventionalists. This technical video presents a swine model designed to train physicians in navigating the spinal venous system, performing embolization injections, observing their spread, and testing new embolization systems for treating CSFVF. Although there are slight anatomical differences, the spinal venous system in swine closely resembles that of humans, including its navigability and employing liquid embolic agents. We successfully embolized multilevel spinal vasculature that can potentially drain into a fistula formation, without any complications.

Background The effectiveness of endovascular thrombectomy (EVT) for low Alberta Stroke Program Early CT score (ASPECTS) stroke patients with occlusion of the second segment of the middle cerebral artery (M2) is unclear. Methods This was a multicenter retrospective study. Patients with M1 or M2 occlusions and low ASPECTS (<6) who underwent successful EVT (modified treatment in cerebral ischemia score of 2b or higher) were included. Primary outcome was futile EVT reperfusion (defined as 90-day modified Rankin scale of 5 or 6). Other outcomes of interest include acceptable outcomes (modified Rankin scale of 3 or less) and intracranial hemorrhage (ICH), and all-cause 90-day mortality. Outcomes for M1 patients were compared to M2 patients with multivariable logistic regression models accounting for potential confounders. Results 173 patients with M1 or M2 occlusions and low ASPECTS (<6) who underwent successful EVT were identified. After multivariable adjustments, M2 patients had significantly higher odds of futile reperfusion (OR 5.48 [95%CI 1.91 to 15.7], p = 0.002), lower odds of acceptable outcomes (OR 0.33 [95%CI 0.12 to 0.89], p = 0.028), and higher odds of all-cause mortality (OR 4.90 [95%CI 1.65 to 14.5], p = 0.004). These findings suggest that EVT's efficacy for low-ASPECTS stroke patients may be diminished for patients with M2 occlusions. M2 occlusion was not significantly associated with ICH. Conclusions Among low-ASEPCTS stroke patients who underwent successful EVT, those with M2 occlusions had significantly higher odds of poor outcome compared to those with M1 occlusions.

An elderly woman presented with coma secondary to acute-on-chronic liver failure and was found to have severe hyperammonaemia. MR scan of brain showed extensive bilateral and symmetric cortical and thalamic fluid-attenuated inversion recovery hyperintense signals and diffusion restriction. How should clinicians address the prognosis of such cases? Postmortem findings from this case provide new insights in pathophysiology.