Citations

Objective: To estimate the relative risk of meningitis after repair of spontaneous lateral skull base cerebrospinal fluid (CSF) leaks through meta-analysis of published studies. Databases Reviewed: PubMed, Medline, Embase, Cochrane, SCI-EXPANDED, ESCI, Epistemonikos, and WHO Global Index Medicus were queried for terms including and related to meningitis, CSF leak, surgery, and spontaneous from inception to April 02, 2024. Methods: Prospective and retrospective studies in any language reporting either preoperative or postoperative rates of meningitis in adults with spontaneous lateral skull base CSF leaks were included. Two reviewers independently screened 2,564 studies and extracted data and evaluated risk of bias in 57 studies that met inclusion criteria. A random effects generalized linear mixed model was used to pool and compare logit transformed risk of meningitis before and after repair. Results: Of 1,310 patients who met inclusion criteria, 1,239 underwent CSF leak repair. Fifty-two studies reported rates of preoperative meningitis, and 27 studies reported rates of postoperative meningitis. Twenty-two studies with a total of 511 patients reported both rates. The average follow-up period of 17 studies reporting duration of follow-up was 23.1 months. The preoperative pooled risk of meningitis was 0.16 (95% CI: 0.13–0.25, I 2 = 40.57%). The postoperative pooled risk was considerably lower at 0.01 (95% CI: 0.01–0.14, I 2 = 4.16%). With substantial heterogeneity (I 2 = 62.94%), we observed a relative risk of meningitis after repair of 0.02 (95% CI: 0.00–0.79, p = 0.04). Conclusion: Surgical repair of spontaneous lateral skull base CSF leaks may significantly reduce the risk of adult meningitis.

With the first series of PRRX1 -rearranged tumors published in 2019, the spectrum of these so-called fibroblastic tumors has been expanded. Since then, several smaller case series have been published; however, our understanding of them continues to be quite limited given their rarity. We herein studied 18 additional cases, the largest series to date. Eighteen tumors present in 9 male, 8 female, and 1 nonbinary patient with a median age of 35 years (range: 11 to 70 y) and involved the neck (5), the chest region (4), thigh (3), back (1), shoulder (1), forehead (1), lower leg (1), axilla (1), and the parapharyngeal region (1). Clinical follow-up (9/18 tumors; 50%; median: 10 mo; range: 4 to 40 mo) showed consistent indolent behavior without local recurrences or distant metastases. On morphology, these tumors were characterized by well-circumscription and distinctive peripheral crescent-shaped vessels. They were composed of uniform spindle and round cells growing in short fascicles within often densely hyalinized collagen lacking significant mitotic activity, necrosis, or cytologic atypia. Immunohistochemically, about half of the tested tumors expressed focal to rarely diffuse S100 with occasional co-expression of SOX10. Interestingly, almost half of the tested cases also showed complete loss of RB expression. All but 1 tumor harbored a PRRX1::NCOA1 fusion, while 1 case harbored a novel PRRX1::EP300 fusion. We herein provide additional data on these exceptionally uncommon tumors, expand their molecular spectrum, and compare them to their close morphologic mimics to aid in accurate diagnosis and avoid confusion with potentially more aggressive neoplasms.

Background: Crohn’s disease (CD) is an inflammatory bowel disease (IBD) that is prevalent worldwide. It can affect any segment of the gastrointestinal tract, from the mouth to the anus. When CD affects the anus, perianal fistulizing disease develops. The management of perianal CD is challenging and may require morbid surgery when there is no response to medical therapy. The emergence of novel biologic therapies, namely tumor necrosis alpha (TNF-α) inhibitors, has proven to provide long-term relief and prevent disease-related complications. Perianal CD is, however, refractory or recurrent in up to 80% of patients. One of the reported options to manage perianal CD is hyperbaric oxygen therapy (HBOT), which aims at increasing tissue oxygen saturation in an attempt to promote repair and reverse local inflammation. Data on this approach is scant. Methods: A retrospective review was performed to identify patients with CD at the Mayo Clinic in Rochester who underwent HBOT for perianal disease between 2014 and 2023. Demographic and clinical data were reviewed, including the history of the disease, concomitant medical and surgical therapy and the need for fecal diversion. The HBOT regimen, including the number of sessions and clinical response, were reviewed. Results: Six patients aged from 19 to 60 years underwent HBOT for perianal CD. Two patients had a history of total proctocolectomy with ileal-anal pouch anastomosis (IPAA). All patients except one were on immunosuppressive medication including biologic agents. Four patients had fecal diversion with an ileostomy or colostomy. Patients received between 10 and 40 sessions of HBOT. Four patients reported symptomatic improvement. On physical examination and/or imaging assessment, improvement was noted in one patient. Progression of the perianal disease was noted in all other patients, with all except one requiring an operation in the following year. Conclusions: HBOT may provide symptomatic relief in some patients with refractory perianal CD, but data on its long-term efficacy remains limited.

Introduction: Life-support limits (i.e., code status), the first step in the continuum of palliation and end-of-life (EoL) care, stem from decisions made by patients and their providers to align care near the EoL with patients’ wishes. The pandemic created health care strain that may have influenced life-support limitation practices among patients with serious COVID-19. In this study, we examine variations in life-support limitations (do-not-resuscitate, DNR; do-not-intubate, DNI) depending on the hospital and period of hospitalization. Methods: We included all adults admitted to a hospital in the United States with COVID-19 from January 2020 to December 2021 using the VIRUS registry. Our outcome was any life-support limitation on admission (DNR, DNI, or both) using regression modeling. Main exposures were hospital and period of hospitalization (early vs. late pandemic). Covariates included age, sex, race/ethnicity, comorbidities, and hospitalization diagnoses. Results: There were 42,383 patients from 75 hospitals in the US. The median age was 63 (interquartile range: 50–75), 46.5% were female, and 37.5% were non-Hispanic White. The life-support limitation rate was 7.9%, and the palliative care consultation rate was 2.3%. The odds of life-support limitation were 1.86 (95% CI: 1.6–2.1) depending on the hospital, but the period of hospitalization was not associated with odds of life-support limitation. Older age was associated with the greatest increased odds (4.1 per standard deviation ∼ 17.9 years, 95% CI: 3.9–4.4), followed by comorbidities including paralysis (2.4, 95% CI: 1.8–3.0) and dementia (2.3, 95% CI: 2.0–2.6). Conclusions: After adjusting for patient-level factors, we report significant inter-hospital but no temporal variation in life-support limitation upon admission with COVID-19. Future studies should investigate specific practices that led to health care resilience to temporal practice variations in life-support limitation during the pandemic.

ABSTRACTBackgroundTricuspid regurgitation (TR) is a common occurrence in patients with heart failure (HF), and its role in disease progression has gained attention in recent years. Although TR can worsen clinical outcomes in HF patients, the impact of gender, racial, and socioeconomic factors remains largely unexplored. With growing evidence supporting the role of percutaneous interventions for the treatment of significant TR, understanding these disparities is more crucial than ever.MethodsData were extracted from the National Inpatient and National Readmission 2016–2020 Databases. We used ICD‐10 code I50 to identify the patients primarily admitted for HF and subdivided the cohort into two groups based on the presence or absence of TR. We performed multivariable logistic regression analysis to determine odds of the in‐hospital mortality and multivariable Cox regression analysis to assess the 30‐ and 90‐day hospital readmission in HF patients with and without TR. All the analyses were adjusted for age, gender, insurance status, Charlson comorbidity index, and hospital characteristics. STATA 16 software was used for analysis.ResultsThere was no difference in the in‐hospital mortality among HF patients with and without TR (OR: 1.04, 95% CI 0.94–1.16, p = 0.442) except in certain subgroups of HF patients. HF patients with TR were 6% more likely to have HF‐specific readmission in 30 days (HR: 1.06, 95% CI 1.00–1.13, p = 0.044) and 9% more likely to have HF‐specific readmission in 90 days (HR: 1.09, 95% CI 1.03–1.15, p = 0.002). Subgroup analysis revealed significant gender, racial, and socioeconomic disparities in the in‐hospital mortality and the readmission outcomes of HF patients with TR compared to those without TR.ConclusionIn our population‐based survey analysis, we observed significant gender, racial, and socioeconomic disparities in the clinical outcomes of HF patients with TR compared to those without TR.

Objective Inflammatory bowel disease (IBD) is increasingly recognised in the Middle East, but limited regional data hinder a clear understanding of its burden. We aimed to examine trends in IBD diagnoses, disease phenotypes and predictors of poor outcomes at a major tertiary referral centre in the United Arab Emirates (UAE). Methods In this retrospective observational study, we evaluated diagnostic trends in a cohort of 600 Arab patients between 2002 and June 2025 and analysed detailed phenotypes in a subcohort of 414 patients diagnosed since 2012. Results We observed a nearly 13-fold increase in new IBD diagnoses among Arab patients at our centre between 2002 and 2024. This cohort (median age at diagnosis 25 years; 65% Crohn’s disease (CD; n=269), 35% ulcerative colitis (UC; n=145)) demonstrated a sharper rise in CD compared with UC, with CD being diagnosed at a significantly younger age (median 25 years vs 30 years, p=0.001). A substantial proportion of patients with CD presented with complicated disease defined as stricturing (B2; 22%, n=59), penetrating (B3; 17%, n=46) and perianal (34%, n=92) disease. Ileocolonic (L3) disease was a significant predictor for presenting with a complicated phenotype (OR 3.89). Penetrating (OR 13.9), stricturing (OR 3.38) and perianal (OR 2.22) disease were significant predictors for requiring surgery. 84% of patients with CD and 62% of patients with UC were exposed to advanced therapy. A diagnosis of CD and younger age at diagnosis were associated with a higher likelihood of needing advanced therapy. Conclusions This study provides the most comprehensive data set on IBD diagnoses and phenotypes in the UAE to date, highlighting a pronounced rise in IBD overall and of aggressive disease presentations in CD in particular.

The NCCN Guidelines for Biliary Tract Cancers (BTCs) provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts is convened at least once annually to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. This manuscript focuses on the adjuvant chemotherapy and chemoradiation treatment options for BTCs as well as the systemic treatment recommendations for patients with advanced BTCs.

Sudden death in children and young adults, while uncommon, carries profound clinical and societal implications. Cardiac causes, particularly inherited arrhythmias and cardiomyopathies, account for most cases, though neurologic, toxicologic, traumatic, and infectious etiologies also contribute significantly. This review explores the epidemiology, classification, and pathophysiologic mechanisms of sudden death in this population, emphasizing early clinical warning signs and identifiable risk factors. We also outline diagnostic and preventive strategies, including electrocardiography, genetic testing, and postmortem evaluation. Despite guidelines advocating preparticipation screening, real-world implementation remains inconsistent. Advances in genomics and artificial intelligence offer new opportunities for early risk detection. Finally, we discuss public health interventions such as defibrillator access, cardiopulmonary resuscitation education, and school-based protocols as essential components of a broader prevention strategy.

Abstract Developmental delay and seizures with or without movement abnormalities (OMIM 617836) caused by heterozygous pathogenic variants in the DHDDS gene (DHDDS-CDG) is a rare genetic disease that belongs to the progressive encephalopathy spectrum. It results in cognitive delay in affected children, accompanied by myoclonus, seizures, ataxia and tremor, which worsens over time. DHDDS encodes a subunit of a DHDDS/NUS1 cis-prenyltransferase ( cis- PTase), a branch point enzyme of the mevalonate pathway essential for N-linked glycosylation. We describe the first mouse model of this disease, Dhdds R37H+/- strain, heterozygous for the human recurrent de novo c.110G>A:p.R37H pathogenic variant. Dhdds R37H+/- mice present with seizures, myoclonus and memory deficits associated with reduced density or/and maturity of inhibitory interneurons in the cortex. Multiomics analyses of mouse CNS tissues, together with the enzymatic/structural characterization of the R37H DHDDS mutant protein, reveal that the variant produces a catalytically inactive enzyme and results in a brain dolichol deficit, aberrant glycosylation of brain glycoproteins, including those involved in synaptic transmission and major perturbations in the CNS proteome and lipidome. Acetazolamide, a carbonic anhydrase inhibitor clinically approved for treatment of glaucoma, epilepsy, and intracranial hypertension, and successfully used “off-label” to treat genetic movement disorders, reduces seizure susceptibility to pentylenetetrazol in Dhdds R37H+/- mice, suggesting potential therapeutic value of using this drug in human DHDDS-CDG patients. Together, our results define cis- PTase as a master regulator of CNS development and function and establish that its monoallelic debilitating variants cause a novel congenital disorder of glycosylation associated with aberrant levels of neuronal proteins and lipids.