Mount Sinai Medical Center

Background/Aims Many patients with digestive symptoms describe underlying urinary or gynecologic symptoms, which may increase visceral sensitivity in the abdominopelvic region and amplify distress around digestive symptoms. The aim of this study was to describe the prevalence of urinary and gynecologic symptoms in patients with disorders of gut–brain interaction (DGBI). Methods Consecutive adult patients with a female reproductive tract who were referred for GI behavioral medicine evaluation for DGBI at a tertiary care center between 2022 and 2023 were prospectively evaluated for symptoms associated with urinary and gynecologic dysfunction. Descriptive statistics were conducted to assess the prevalence of these symptoms within this population by anatomic region affected (esophagus, stomach, and bowel). Results A total of 432 patients were included in our cohort with a mean (SD) age of 40.0 years [Q1;Q3 29.0–52.0], with a predominantly White population (86.1%). Dysmenorrhea (61.0%) and menorrhagia (58.6%) were commonly reported among women with digestive symptoms. Urinary symptoms were less common, with 18.7% reporting pain with urination, 33.0% reporting difficulty voiding urine, and 26.1% reporting a history of frequent UTIs. 23% of women experienced ≥ 4 urinary/gynecologic symptoms. There were no significant differences in the type of urogynecologic symptoms reported based on the affected area of the GI tract. Conclusion Urogynecologic symptoms are common among patients with DGBIs affecting the entirety of the GI tract. We presume the presence of these comorbid symptoms is likely to impact symptom severity, quality of life, and could affect treatment response. Future studies are necessary to understand the mechanisms behind these shared conditions as well as develop effective treatments that address their overlap.

Objective Electronic health records (EHRs) are increasingly used to conduct research and evaluate epilepsy quality of care. We examined the accuracy of International Classification of Diseases, 9th and 10th Revision, Clinical Modification (ICD‐9‐CM, ICD‐10‐CM)‐ and antiseizure medicine (ASM)‐based algorithms for adult epilepsy. Methods Data from a diverse New York multicenter EHR were queried to identify encounters between January 1, 2012 and September 20, 2018 coded with an epilepsy/seizure ICD‐CM code or an ASM. Eight hundred adults were randomly selected (350 with epilepsy‐related codes, 150 with an ASM, and 300 with drug‐resistant epilepsy codes). With chart review defined as the reference standard, sensitivity (Sn), specificity (Sp), negative predictive value (NPV), positive predictive value (PPV), and Youden index (YI) were calculated to evaluate various ICD‐9‐CM‐, ICD‐10‐CM‐, ± ASM‐based algorithms' accuracy in predicting epilepsy. Results Ninety‐four algorithms were tested. A total of 435 (54.4%) patients had definite epilepsy. Estimates ranged as follows: YI = .18–.68, Sn = .59–.95, Sp = .52–.97, PPV = .67–.92, and NPV = .51–.93. The best algorithms were as follows. Highest YI for ICD‐9‐CM was single encounter with 345 (except 345.2 or 345.3) or 345.2, 345.3, or 780.3 with an ASM (Sn = .95, Sp = .73, PPV = .81, NPV = .92, YI = .68). Highest Y1 for ICD‐10‐CM was one encounter with G40 in primary diagnostic position or ≥2 encounters with G40 in any diagnostic position (Sn = .82, Sp = .85, PPV = .87, NPV = .80, YI = .67). Highest sensitivity was any encounter with ICD‐9‐CM 345 or 780.39 or ICD‐10‐CM G40, G41, or R56.9 (Sn = .96, Sp = .57, PPV = .73, NPV = .93, YI = .53). Highest specificity was ≥1 hospitalization with ICD‐9‐CM 345.x (except 345.2 and 345.3) or ICD‐10‐CM G40.x (Sn = .21, Sp = .97, PPV = .89, NPV = .51, YI = .18). Significance We identified ICD‐9/10‐CM‐based case definitions (with and without ASM) that were sensitive and specific for epilepsy. Ultimately, extensive algorithms are provided to help inform case definition selection according to future study aims.

Nerves are integral to the adenoid cystic carcinoma (ACC) microenvironment. The strong association of ACC with perineural invasion (PNI) is considered a hallmark of this disease. In human salivary ACC, we identify intratumoral, small-caliber, disorganized sympathetic nerves not observed in other salivary neoplasms. Norepinephrine or sympathetic ganglia explants enhance ACC proliferation in vitro. Two novel orthotopic ACC patient-derived xenograft (PDX) models recapitulate ACC morphology and demonstrate sympathetic innervation. Pharmacologic or surgical blockade of sympathetic nerves decreases ACC PDX growth. Bulk RNA sequencing of salivary ACC reveals correlations between noradrenergic nerve development signatures and worse patient survival. Metastatic ACC foci exhibit lower nerve signature gene expression levels than primary ACC. Sympathetic innervation in ACC is distinct from PNI and reflects tumor axonogenesis driven by noradrenergic neural development programs. These programs support ACC progression, are associated with poor prognosis, and may be inhibited as a therapeutic strategy.

Obesity-related hypertension (HTN) is a growing global health concern, being a significant contributor to cardiovascular morbidity and mortality. The article reviews the complex pathophysiological mechanisms involved in the link between obesity and HTN, including neurohormonal activation, inflammation, insulin resistance, and endothelial dysfunction. The role of adipokines, specifically leptin and adiponectin, in blood pressure regulation is highlighted, along with the impact of advanced glycation end-products on vascular function. We discuss the effectiveness of lifestyle therapies, including weight loss, and diet for the management of obesity HTN. We also discuss the utilization of pharmacologic agents, including GLP-1 receptor agonists, and the impact of bariatric surgery on long-term blood pressure control. Despite enhanced treatment, significant barriers to treatment exist, including obesity stigma, limited access to health care, and adherence problems. Future research must focus on personalized approaches, like pharmacogenomics, to optimize hypertension treatment in the obese.

Chelation therapy is a promising approach to mitigating health risks associated with toxic metal exposure, which contributes to cardiovascular disease, neurotoxicity, and other chronic conditions. Ethylenediamine edetate disodium (EDTA) is widely used, but its optimal dosing strategy remains unclear. This study evaluates the dose-dependent efficacy of EDTA in mobilizing toxic metals, including lead (Pb), cadmium (Cd), and gadolinium (Gd), while minimizing the loss of essential metals like copper (Cu) and manganese (Mn) to optimize therapeutic safety and efficacy. Ten volunteers (≥50 years) received three weekly EDTA infusions at doses of 0.5 g, 1 g, and 3 g over 30 minutes, 1 hour, and 3 hours, respectively. Urine and blood samples were analyzed pre- and post-infusion to assess metal excretion dynamics. Pb excretion increased by 2 200% at 0.5 g, with only a marginal gain at higher doses (3 300%), suggesting low-dose efficacy. Cd clearance required 3 g due to its strong tissue binding. Notably, Gd excretion increased by up to 78 000% even at 0.5 g, highlighting EDTA's potential to reduce long-term Gd burden post-MRI. Essential metal excretion varied, with Mn and Zn loss increasing at higher doses, underscoring the need for dose optimization. The 0.5 g dose effectively mobilized Pb and Gd while minimizing essential metal depletion, reducing infusion time to 30 minutes, and improving patient compliance. These findings align with TACT and TACT 2 studies, reinforcing EDTA's long-term benefits in Pb reduction and supporting low-dose EDTA as a safe, efficient, and well-tolerated detoxification strategy.

Introduction About one-third of adults in the USA have some grade of hepatic steatosis. Coronary artery calcium (CAC) scans contain more information than currently reported. We previously reported new artificial intelligence (AI) algorithms applied to CAC scans for opportunistic measurement of bone mineral density, cardiac chamber volumes, left ventricular mass, and other imaging biomarkers collectively referred to as AI-cardiovascular disease (CVD). In this study, we investigate a new AI-CVD algorithm for opportunistic measurement of liver steatosis. Methods We applied AI-CVD to CAC scans from 5702 asymptomatic individuals (52% female, age 62±10 years) in the Multi-Ethnic Study of Atherosclerosis. Liver attenuation index (LAI) was measured using the percentage of voxels below 40 Hounsfield units. We used Cox proportional hazards regression to examine the association of LAI with incident CVD and mortality over 15 years, adjusted for CVD risk factors and the Agatston CAC score. Results A total of 751 CVD and 1343 deaths accrued over 15 years. Mean±SD LAI in females and males was 38±15% and 43±13%, respectively. Participants in the highest versus lowest quartile of LAI had greater incidence of CVD over 15 years: 19% (95% CI 17% to 22%) vs 12% (10% to 14%), respectively, p<0.0001. Individuals in the highest quartile of LAI (Q4) had a higher risk of CVD (HR 1.43, 95% CI 1.08 to 1.89), stroke (HR 1.77, 95% CI 1.09 to 2.88), and all-cause mortality (HR 1.36, 95% CI 1.10 to 1.67) compared with those in the lowest quartile (Q1), independent of CVD risk factors. Conclusion AI-enabled liver steatosis measurement in CAC scans provides opportunistic and actionable information for early detection of individuals at elevated risk of CVD events and mortality, without additional radiation.

Objective: We aimed to study the association of patient’s body mass index (BMI) with postoperative complications in patients surgically treated for endometrial intraepithelial neoplasia, with and without sentinel lymph node biopsy. Methods: A cohort study using the prospective National Surgical Quality Improvement Program database. Women with endometrial intraepithelial neoplasia on postoperative pathology who underwent minimally invasive hysterectomy from January 2012 to December 2020 were included. The cohort was dichotomized based on the performance of sentinel lymph node biopsy. We analyzed postoperative complications based on the World Health Organization (WHO) categories of BMI. Results: A total of 4428 patients met the inclusion criteria. Of those, 584 (13.2%) had sentinel lymph node biopsy. Overall, 76.5% of patients (n = 3389) were obese (BMI > 30.0), with 1840 (41.6%) patients of BMI ≥ 40.0. The rate of any complications was 6.0% (n = 264), major complications 2.3% (n = 101), and minor complications 4.2% (n = 187). When comparing the rate of any complications between patients who had sentinel lymph node biopsy vs. those without a sentinel lymph node biopsy procedure, stratified by BMI category, there was no association between sentinel lymph node biopsy performance and any complications in any of the BMI categories. In a multivariable binary regression analysis, BMI and the performance of sentinel lymph node biopsy were not independently associated with any complication [adjusted odds ratio (aORs) 1.001, 95% confidence interval (CI) (0.98–1.01), and aORs 1.1, 95% CI (0.82–1.65), respectively]. In an analysis of the cohort of patients who underwent sentinel lymph node biopsy, there was no association between the rates of any major or minor complications with BMI categories or obesity. ROC analyses for the association between BMI and occurrence of any major or minor complications had a low performance. Conclusions: In minimally invasive surgery for endometrial intraepithelial neoplasia, there is no association between body mass index and increased risk for postoperative complications when performing hysterectomy with sentinel lymph node biopsy versus hysterectomy alone.

Human microglial heterogeneity has been largely described using transcriptomic data. Here, we introduce a microglial proteomic data resource and a Cellular Indexing of Transcriptomes and Epitopes by Sequencing panel enhanced with antibodies targeting 17 microglial cell surface proteins (mCITE-Seq). We evaluated mCITE-Seq on HMC3 microglia-like cells, induced-pluripotent stem cell-derived microglia (iMG), and freshly isolated primary human microglia. We identified novel protein microglial markers such as CD51 and relate expression of 101 cell surface proteins to transcriptional programs. This results in the identification and validation of three protein marker combinations with which to purify microglia enriched with each of 23 transcriptional programs; for example, CD49D, HLA-DR and CD32 enrich for GPNMB high (“disease associated”) microglia. Further, we identify and validate proteins - SIRPA, PDPN and CD162 – that differentiate microglia from infiltrating macrophages. The mCITE-Seq panel enables the transition from RNA-based classification and facilitates the functional characterization and harmonization of model systems.

Background Acellular dermal matrices (ADMs) are biologic meshes commonly used in implant-based breast reconstruction (IBBR) procedures to provide implant support and coverage. Although the etiology is not well understood, increasing preclinical and clinical evidence suggest that ADMs may help prevent capsular contracture, a frequent complication of IBBR, by modulating the inflammatory response in the tissue surrounding breast implants. The objective of this narrative review is to discuss the evidence supporting the role of inflammation in capsular contracture following IBBR without ADM, and to characterize the potential mechanism(s) by which ADMs may reduce the incidence of capsular contracture in IBBR. Methods Relevant studies in English published up to December 31, 2023, were identified from 4 databases (BIOSIS Previews, Embase, MEDLINE, and Northern Light Life Sciences Conference Abstracts) using search terms such as “breast” and “capsular contracture.” Results This review discusses the potential factors (eg, expander-to-implant reconstruction, diminished collagen integrity, postmastectomy radiation therapy, surface of implant, plane of placement, incision type, hematoma, seroma, postoperative infection, and biofilm) and emerging biomarkers (eg, NRG1 , IL-8 , TIMP-1, TIMP-2, TIMP-4 , MMP2, MMP12 , ACAN , SAA1 , TNFSF11 , and hyaluronan) that may be able to predict capsular contracture. The available evidence that tissue integration of ADMs modulates the wound healing process and inflammation, and the available clinical evidence, which indicates that ADMs may decrease rates of capsular contracture following postmastectomy radiation therapy, are summarized. Conclusions The studies summarized in this review suggest that ADMs may reduce the likelihood of capsular contracture in IBRR compared with no ADM use.

Background Studies have shown mixed results regarding the association between irritable bowel syndrome (IBS) and metabolic syndrome (MS); This study aimed to assess the susceptibility of IBS patients to MS and its individual components. Methods PubMed, Scopus, Embase, and Web of Science were searched on 1/1/2023. Eligible studies were screened, and data on study characteristics, IBS diagnostic criteria, and metabolic syndrome components were extracted. Data were analysed in RevMan 5.4, with results reported as relative risk (RR) or mean difference (MD) and 95% confidence intervals. Statistical significance was set at p < 0.05. Results IBS was associated with an increased risk of MS (RR = 2.05, 95% CI = 1.50–2.79, p < 0.00001), with a higher risk among IBS‐D patients (RR = 3.09, 95% CI = 2.41–3.97, p < 0.00001). IBS patients showed increased HOMA‐IR (MD = 0.21, 95% CI = 0.15–0.26, p < 0.00001), higher obesity risk (RR = 1.46, 95% CI = 1.10–1.93, p = 0.009), elevated BMI (MD = 1.51, 95% CI = 0.98–2.03, p‐value < 0.00001), waist circumference (MD = 5.01, 95% CI = 1.29–8.72, p = 0.008), and an association with systolic hypertension (MD = −0.50, 95% CI = −0.60 to −0.40, p‐value < 0.00001). IBS was also linked to higher LDL (MD = 5.98, 95% CI = 0.91–11.05, p = 0.02), total cholesterol (MD = 12.21, 95% CI = 6.23–18.18, p < 0.0001), and triglycerides (MD = 11.93, 95% CI = 11.55–12.31, p < 0.00001). Conclusions This analysis indicates a potential association between IBS and metabolic syndrome, including its components such as obesity, hypertension, and lipid profile abnormalities. However, significant heterogeneity among studies limits the generalisability of these findings. Clinicians should remain aware of the possible link and consider individualised preventive and management strategies.