Citations

Abstract Objective Perimenopause is an under-recognized life stage that may be accompanied by complex and fluctuating symptoms. We aimed to quantify the prevalence of perimenopause uncertainty and explore the underlying drivers. Methods We conducted a mixed-methods study based on a cross-sectional survey of U.S. women aged 35 years and above (N=7,640). Closed-ended responses were analyzed to estimate the prevalence of perimenopause uncertainty with subgroup differences investigated by age and symptom severity. Content analysis of free-text responses (n=409) was conducted to identify the main uncertainty drivers. Results Overall, 34% of participants reported being unsure of their reproductive stage. Uncertainty peaked among those aged 40-44 (42%) and was highest among those with severe symptom burden (37%). The content analysis revealed three main uncertainty drivers. Symptom confusion and attribution was the most common (56%), reflecting difficulties interpreting bodily changes and distinguishing perimenopause from other causes. Knowledge gaps and information seeking accounted for 28% of responses, highlighting limited health literacy, assumptions about age, and active searches for evidence. Barriers to confirmation and care (16%) described dismissive healthcare encounters and reluctance to acknowledge perimenopause. Younger women (35-39 years) were more likely to cite knowledge gaps, while healthcare barriers peaked in the 40-44 age group. Conclusion Perimenopause uncertainty is a prevalent and clinically meaningful challenge. This uncertainty is conceptually distinct from illness-focused models: it is a universal transition with ambiguity and often lack of validation. Better symptom recognition and targeted communication is a crucial first step toward improving women’s awareness and support during perimenopause.

Introduction: Clostridioides difficile infection (CDI) is a major complication in patients with inflammatory bowel disease (IBD), contributing to increased morbidity, mortality, and health care burden. This study aimed to evaluate national trends and clinical outcomes associated with CDI in hospitalized IBD patients in the United States. Methods: We conducted a retrospective cohort study using the National Inpatient Sample (NIS) from 2012 to 2021. Adult patients hospitalized with a primary or secondary diagnosis of IBD (Crohn’s disease or ulcerative colitis) were stratified into 2 groups by the status of CDI diagnosis (either primary or secondary diagnosis). Demographic characteristics, hospital outcomes, and complications were compared between CDI and non-CDI cohorts. Multivariable logistic regression was used to identify independent predictors of in-hospital mortality, septic shock, and venous thromboembolism (VTE). Results: Among 4,193,564 hospitalized IBD patients, 534,190 (12.7%) had CDI. CDI patients were older (mean: 68.8 vs 53.3 y, P < 0.001), with higher in-hospital mortality (3.6% vs 2.0%, P < 0.001), VTE (23.7% vs 6.2%, P < 0.001), septic shock (5.4% vs 4.0%, P < 0.001), and mechanical ventilation use (4.2% vs 2.8%, P < 0.001). Ulcerative colitis was more frequently associated with CDI than Crohn’s disease (30.3% vs 25.0%, P < 0.001) and independently predicted septic shock (OR: 1.09) and VTE (OR: 1.06) but was associated with lower mortality (OR: 0.81). Conclusion: The presence of CDI in hospitalized patients with IBD led to significantly worse outcomes. Ulcerative colitis is more commonly associated with CDI and increased risk of complications. These findings highlight the need for early detection, preventive strategies, and tailored management of CDI in the IBD population.

Background: Mastocytic enterocolitis has been proposed as a cause of chronic diarrhea and abdominal pain, characterized by increased mast cells in gastrointestinal mucosal biopsies. However, its clinical significance remains uncertain. Methods: We present a case report of a patient identified to have high levels of mast cells on gastrointestinal biopsies. We then reviewed cases at Mayo Clinic where patients had >20 mast cells per high-power field (HPF) on gastrointestinal biopsies. Patients with alternative explanations for mast cell elevation, including systemic mastocytosis were excluded. We analyzed demographics, clinical presentations, pathology reports, serum and urine mast cell mediators, inflammatory markers, bone marrow biopsies, motility testing, and treatment responses. Results: We identified 42 patients (30 female and 12 male) with elevated mast cells on biopsy (mean age: 41 y, range: 17 to 81). Mast cells were quantified using KIT (CD117) staining, with no abnormal clumping or morphology, and CD25 immunostaining was negative in all cases. Eosinophilic infiltration was absent in all but one case. Small intestinal bacterial overgrowth (SIBO) was found in 78% of patients tested. Treatments varied widely, with antihistamines and cromolyn being the most common. Among 21 patients with sufficient follow-up, only 5 (24%) reported partial or complete symptom improvement, while 76% experienced persistent symptoms. Conclusion: Routine assessment of mast cells on gastrointestinal biopsies is not supported by our findings. Elevated mucosal mast cells, in the absence of systemic mast cell disorders, may not indicate a distinct disease entity. Evaluation should focus on ruling out other inflammatory, allergic, infectious, and motility disorders, as well as SIBO. Further research is needed to determine the clinical significance of increased mucosal mast cells and their role in gastrointestinal symptomatology.

Background and Objectives: There are many well-described approaches to symptomatic ventral hernia management; however, there remains a significant patient population with limited options for a durable ventral hernia repair with a reasonable risk of infection and recurrence. Drawing from the orthopedic literature, we changed our approach to this clinical problem and developed a palliative ventral hernioplasty pathway. Materials and Methods: A retrospective review (2017–2019) of patients’ palliative ventral hernioplasty was performed. Results: In total, 43 patients included, with a female preponderance of 24 (58.6%) and a mean age 61.5 ± 11.5 years. The mean BMI was 38.1 kg/m2 (IQR: 25.4–62), and 28 patients (65.1%) had a history of prior wound/mesh infection. Urgent repair was performed in 14 patients. Overall polypropylene prosthetic was implanted in 26 patients, and bioprosthetic/absorbable mesh was used in the remaining. The mean surface area of the implanted mesh was 561 cm2. The most common wound complications identified were skin separation (30.2%) and seroma formation (48.8%). Hernia recurrence occurred in four (9.3%) patients, with a mean follow-up of 24.1 months (9–37). Three patients had central lightweight mesh rupture and one had a recurrence (bioprosthetic mesh); all were subsequently repaired. Conclusions: Despite the small number of patients, our palliative ventral hernia repair pathway offers durable repair with an acceptable risk of recurrence and mesh infection in patients who would otherwise be considered nonoperative.

Mucosal-associated invariant T (MAIT) cells are abundant innate-like T lymphocytes in the human liver which can provide antimicrobial defense, amplify inflammatory processes and mediate tissue repair and fibrosis depending on microenvironmental cues. Chronic liver diseases of diverse etiologies, including viral hepatitis, metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, biliary tract disease, autoimmune hepatitis and hepatocellular carcinoma are accompanied by numerical and functional adjustments in the MAIT cell population. In this review, we integrate existing data on MAIT cell markers and functions in diverse liver diseases, comparing how these cells are similarly or differentially shaped by distinct pathogenic contexts. Finally, we propose a spatially anchored conceptual and technical framework to study MAIT cell biology in liver disease.

Acute myocardial infarction (AMI) is a significant factor leading to the death of patients with coronary heart disease. Both AMI and reperfusion therapy after AMI cause myocardial cell death, which plays a significant role in heart failure. Following the restoration of blood flow during reperfusion, myocardial cells generate a large amount of oxygen free radicals, causing various forms of myocardial ischemia–reperfusion (IR) injury (IRI), ultimately leading to multiple types of myocardial cell death, among which apoptosis and necroptosis are the two major types. Given the extremely limited regenerative capacity of myocardium, inhibiting myocardial cell apoptosis and necroptosis is a key strategy for reducing mortality in patients with AMI. Both apoptosis and necroptosis are regulated by the BCL2 family of proteins, which were modulated by multiple signaling pathways, converging at BAK/BAX-mediated mitochondrial outer membrane permeabilization (MOMP), as well as mitochondrial inner membrane permeabilization (MIMP). BAK/BAX double knock out (DKO) mice showed reduced cell apoptosis, necroptosis, and infarct size in AMI animal models compared to wild type. This review describes the role of BCL2 family proteins in regulating apoptotic and necroptotic myocardial cell death during AMI and IR, explores the upstream pathways modulating apoptosis and necroptosis, and summarizes the recent advances in targeting BAK and/or BAX for cardiac protection. In addition, targeted delivery of BAK/BAX inhibitors to cardiomyocytes during AMI or myocardial IR has the potential to reduce myocardial cell death and therefore lower the mortality and enhance long-term prognosis for myocardial infarction patients.

Background/Objectives: Speech and motor control share overlapping neural mechanisms, yet their quantitative relationships in Parkinson’s disease (PD) remain underexplored. This study investigated bidirectional associations between acoustic voice features and objective motor metrics to better understand how vocal and motor systems relate in PD. Methods: Cross-sectional baseline data from participants in a randomized neuromodulation trial were analyzed (n = 13). Motor performance was captured using an Integrated Motion Analysis Suite (IMAS), which enabled quantitative, objective characterization of motor performance during balance, gait, and upper- and lower-limb tasks. Acoustic analyses included harmonic-to-noise ratio (HNR), smoothed cepstral peak prominence (CPPS), jitter, shimmer, median fundamental frequency (F0), F0 standard deviation (SD F0), and voice intensity. Univariate linear regressions were conducted in both directions (voice ↔ motor), as well as partial correlations controlling for PD motor symptom severity. Results: When modeling voice outcomes, faster motor performance and shorter movement durations were associated with acoustically clearer voice features (e.g., higher elbow flexion-extension peak speed with higher voice HNR, β = 8.5, R2 = 0.56, p = 0.01). Similarly, when modeling motor outcomes, clearer voice measures were linked with faster movement speed and shorter movement durations (e.g., higher voice HNR with higher peak movement speed in elbow flexion/extension, β = 0.07, R2 = 0.56, p = 0.01). Conclusions: Voice and motor measures in PD showed significant bidirectional associations, suggesting shared sensorimotor control. These exploratory findings, while limited by sample size, support the feasibility of integrated multimodal assessment for future longitudinal studies.

Background: Studies in the past have demonstrated an association between sarcoidosis and pulmonary embolism (PE), but little is known about its impact, especially in young adults. We aim to determine the burden and impact of PE in young adults hospitalized with sarcoidosis. Methods: This study investigates the prevalence and consequences of PE in young adults aged 18–44 years hospitalized with sarcoidosis using data from the National Inpatient Sample (2016–2020) with relevant International Classification of Diseases (ICD)-10 codes. This study aims to address the primary outcomes of the burden and trends of PE and its associated impact on in-hospital mortality. Additionally, it explores secondary outcomes such as healthcare resource utilization and discharge patterns. Results: Among 50,385 young adults (median age 37 years) hospitalized with sarcoidosis, 1120 had PE, showing a linear increase from 2% in 2016 to 2.9% ( P < 0.001) in 2020. The sarcoidosis–PE+ group, predominantly in young blacks, exhibited a higher prevalence of comorbidities such as obesity, smoking, drug use, peripheral vascular disease, hypothyroidism and prior history of venous thrombus embolism. In contrast, the sarcoidosis–PE− group had a higher prevalence of diabetes (with/without chronic complication), hyperlipidemia and chronic pulmonary disease. Multivariable regression analysis adjusted for all potential sociodemographic and comorbid variables showed higher odds of all-cause mortality (odds ratio [OR]: 2.92, 95% confidence interval [CI]: 1.18–7.24, P < 0.02) in the sarcoidosis–PE+ group as compared to the sarcoidosis–PE− group. The sarcoidosis–PE+ group also had higher hospital costs and length of stay. Conclusion: The higher odds of in-hospital mortality with an increased length of stay and hospital cost observed in the sarcoidosis–PE+ group highlight the often underreported complications of sarcoidosis, particularly in a younger demographic. The relevance of this study stems from its potential to uncover trends that could lead to improved diagnostic and therapeutic strategies.

Abstract There is debate on the predictive value of multiday seizure cycles versus simple statistical baselines. Multidien seizure cyclicity is a prevalent, patient‐specific phenomenon with promise for epilepsy management. We challenge the assertion that cycle tracking is no better than a moving average, which is an inherently retrospective model that lags changes in seizure likelihood. This commentary compared a causal cyclic forecast to a prospectively applied moving average across a large seizure diary cohort ( n = 768) and two gold‐standard chronic EEG cohorts ( n = 24). For the EEG and diary cohorts, cycle tracking demonstrated significantly superior accuracy to the moving average for both hourly and daily forecasts ( p < 0.0001), using multiple performance metrics. These results confirm that event‐based cyclical models offer more accurate, simulated real‐world forecasts. Robust forecasting tools must prioritize the detection and modeling of seizure cycles to move beyond simple baseline performance and provide actionable clinical utility.

Abstract High‐titer glutamic acid decarboxylase 65 (GAD65) antibodies (>20 nmol/L) are linked to chronic focal epilepsy, usually of temporal regional onset. Identification of these antibodies has treatment and prognostic implications. We compared patients with drug‐resistant epilepsy and high‐titer GAD65 antibodies to an age‐ and sex‐matched control group with drug‐resistant GAD65 antibody–negative temporal lobe epilepsy. From 1432 patients presented at a single‐center surgical epilepsy conference (2007–2024), we identified 15 patients (1% from surgical epilepsy conference: 13 female, 86.7%) with high‐titer serum GAD65 antibodies (median serum titer = 960 nmol/L; range 34–4678). The median age at epilepsy onset was 25 years (range 4–44). All had temporal regional‐onset epilepsy; 53% had bitemporal seizures. Three patients had limbic encephalitis, and three developed mesial temporal sclerosis. Those with GAD65 antibody–associated epilepsy were more likely to have depression and/or anxiety and less likely to undergo resection after evaluation than those in the control group. Although seizure types, electroencephalography (EEG), imaging, and autoimmune history were not statistically significantly different from the control group, we found that musicogenic seizures, limbic encephalitis, and type 1 diabetes occurred only in GAD65‐positive patients. These features, when present, may suggest an autoimmune etiology and warrant antibody testing. Identifying patients with GAD65 antibody–associated epilepsy is important due to its drug resistance, lower rate of satisfactory surgical outcomes, and potential responsiveness to immunotherapy. Further research is needed to define the optimal treatment and distinguish this subgroup from other causes of drug‐resistant epilepsy.