Citations

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a promising therapeutic option for women with polycystic ovary syndrome (PCOS). Clinical trials and data demonstrate significant improvements in body weight, insulin resistance, hyperandrogenism, and, in some studies, menstrual regularity and reproductive outcomes. However, the current evidence base remains disproportionately focused on short-term metabolic and anthropometric endpoints, while outcomes most relevant to patients—including treatment satisfaction, gastrointestinal tolerability, psychological well-being, body image, fertility planning, financial burden, and long-term adherence—remain inadequately characterized. Methods: We searched PubMed and Google Scholar for English-language literature published between 2021 and 2026, using structured keyword searches. This narrative review evaluates the literature on GLP-1RA use in PCOS beyond weight-focused outcomes, examining mechanisms of action, comparative tolerability across agents, and patient-centered domains including quality of life, eating behavior, and reproductive planning. Results: The published literature reveals a substantial gap between trial-reported completion rates and treatment success, and actual persistence and patient satisfaction. This discrepancy is particularly consequential in PCOS, where treatment decisions intersect with high baseline rates of depression, anxiety, and body image disturbance, and where ovulatory benefits must be weighed against mandatory discontinuation before conception. Conclusions: We identify a systematic absence of validated patient-reported outcome measures, standardized core outcome sets, and long-term follow-up data after treatment withdrawal. This review proposes a research agenda prioritizing patient-centered endpoints as co-primary outcomes, structured assessment of acceptability and persistence, qualitative and mixed-methods approaches, and a dedicated study of fertility planning and treatment interruption.

Photoplethysmography (PPG) is a non-invasive optical technique commonly used to measure heart rate and oxygen saturation, but its waveform contains additional physiological information that can be analyzed using artificial intelligence (AI). This narrative review summarizes the emerging applications of AI-based PPG in cardiovascular, respiratory, sleep, hemodynamic, pregnancy-related, and portal-hypertension assessment, with the aim of evaluating its potential beyond conventional monitoring and identifying barriers to clinical translation. The literature search was conducted using PubMed, Google Scholar, IEEE Xplore, ScienceDirect, and SpringerLink. Additional relevant studies were identified through screening the reference lists of included articles. Studies published between 2002 and 2026 were identified to capture the development of PPG from conventional monitoring to newer AI-based applications. Human studies were prioritized, while relevant computational, simulated, synthetic, ex vivo, and technical studies were also included. Studies unrelated to PPG, duplicates, and studies with limited relevance were excluded. A total of 96 references were included, covering AI approaches such as convolutional and deep neural networks, ensemble methods, transfer learning, U-Net, generative adversarial networks, and Transformer-based models. Overall, the reviewed evidence suggests that AI-based PPG may support blood pressure estimation, atrial fibrillation detection, sleep and respiratory monitoring, vascular aging assessment, pulmonary hypertension screening, preeclampsia assessment, volume-status and compensatory-reserve assessment, and exploratory assessment related to portal hypertension. However, clinical translation remains limited by motion artifacts, sensor and measurement-site variability, skin-pigmentation-related bias, physiological and environmental influences, heterogeneous methods, limited external validation, and inconsistent clinical and regulatory standards.

Abstract Skin and soft tissues infections (SSTIs) are common conditions, affecting millions worldwide. SSTIs range from uncomplicated cellulitis to necrotizing fasciitis and can be divided into non-purulent and purulent forms. Non-purulent SSTI is most commonly associated with beta-haemolytic streptococci, while purulent SSTI is typically associated with Staphylococcus aureus . Cellulitis most commonly presents with acute warmth, pain, tenderness to palpation, erythema, and oedema. Skin abscess typically presents with a fluctuant tender area with erythema. Laboratory testing is of limited use in most patients. Point-of-care ultrasound is useful for distinguishing cellulitis from abscess if the diagnosis is unclear. Management of SSTI includes antibiotics such as penicillin VK, dicloxacillin, or a cephalosporin, while treatment for skin abscess includes incision and drainage, with antibiotics recommended in select patients. Patients should elevate the affected extremity when possible, and non-steroidal anti-inflammatory drugs may reduce pain and inflammation. The effectiveness of decolonization for patients with recurrent cellulitis or skin abscess is controversial. While most patients with cellulitis or skin abscess are appropriate for discharge with follow-up, patients with sepsis and those with challenges adhering to therapy, immunosuppression, or failed outpatient therapy should be referred to the emergency department. Novel antibiotics such as tedizolid, delafloxacin, omadacycline, and ceftaroline may be considered in select cases.

Abstract BRCA1 -deficient cancers experience persistent replication stress and structural genome instability yet retain the capacity for sustained proliferation, implying reliance on compensatory genome-maintenance mechanisms. Here, we establish BRCA1–FANCM synthetic lethality in human BRCA1 -deficient breast cancer and exploit temporally controlled FANCM depletion to capture genome evolution over successive cell divisions before declining cellular fitness becomes limiting. We show that FANCM restrains genome-wide structural variation in BRCA1 -deficient breast cancer cells under endogenous replication stress. FANCM loss amplifies the characteristic BRCA1 -associated short tandem duplication (TD) phenotype while permitting larger, including megabase-scale, TDs and diverse rearrangements to emerge. Newly emerged TDs preferentially associate with Pol II-occupied regions, and FANCM depletion increases proximity between the replication machinery and elongating RNAPII in BRCA1 -mutant breast cancer cells, linking FANCM-mediated genome protection to transcription–replication encounters. BRCA1 -altered human tumors with low FANCM expression recapitulate key features of this phenotype, while genome–transcriptome integration links newly emerged SVs to configuration-dependent local transcriptional changes. Together, these findings establish FANCM as a replication-stress safeguard coupling survival to restraint of structural genome evolution.

ABSTRACT Introduction Patients often receive propofol for sedation and clevidipine for hypertension in the intensive care unit. Both agents are formulated as a lipid emulsion, which may increase the risk of hypertriglyceridemia and acute pancreatitis with their coadministration. We aimed to determine the incidence of hypertriglyceridemia and acute pancreatitis with concurrent administration of propofol and clevidipine and identify patient risk factors for hypertriglyceridemia. Methods This was a multicenter retrospective study of adult patients (≥ 18 years old) receiving concurrent propofol and clevidipine infusions for ≥ 6 h. The primary outcome was the frequency of triglyceride levels greater than 400 mg/dL and acute pancreatitis. The secondary outcome was risk factors associated with hypertriglyceridemia during concurrent propofol and clevidipine infusions until both infusions had been discontinued. Univariable and multivariable logistic regression analyses were used to assess risk factors of hypertriglyceridemia in patients receiving concurrent propofol and clevidipine infusions. Results Across 1,226 patients, the median duration of infusion overlap was 12.4 [interquartile range (IQR) 8.3, 22.7] hours. The mean age of the cohort was 59.6 [standard deviation (SD) 14.9] years, and 59.4% were male. Assuming those without a triglyceride level drawn did not have hypertriglyceridemia, hypertriglyceridemia after initiation of propofol and clevidipine infusion was found in 7.7% [95% confidence interval (CI) 6.3% to 9.3%] of the entire cohort. Twenty‐six patients (2.1%) had a diagnosis of pancreatitis after initiation of lipid infusions, of which 12 cases were possibly infusion‐related, and one case was likely infusion‐related. After calculating the Naranjo Scale, all 13 cases of pancreatitis were possibly related to propofol or clevidipine infusions. Based on a multivariable logistic regression of those with a triglyceride level available, risk factors for hypertriglyceridemia included pancreatitis within the past 5 years [adjusted odds ratio (aOR) 2.77, 95% CI, 1.23 to 6.23] and statin use (aOR 1.94, 95% CI, 1.13 to 3.34). Conclusions In our cohort of patients receiving concurrent propofol and clevidipine, the frequency of hypertriglyceridemia and acute pancreatitis was low. Further comparative studies are warranted to assess the risk of pancreatitis with the addition of clevidipine to propofol.

Cardiac allograft vasculopathy (CAV) remains a leading cause of graft failure after heart transplantation, yet an early, non-invasive risk stratification tool is not available. Artificial intelligence electrocardiography (AI-ECG) can estimate biological heart age, and it has been associated with cardiovascular risk. Its deviation with chronological age, called delta age, and its utility in the prediction of CAV has never been explored. We conducted a retrospective single-center study for heart transplant recipients bridged with Impella 5.5 (Abiomed, Danvers, MA, USA) at Mayo Clinic Florida (2020–2023). ΔAge was calculated at discharge and 1-year post-transplant. The primary outcome was confirmed CAV at 1 year. Univariate and multivariable logistic regression models were used to assess the independent association between the ΔAge and the development of CAV, with discrimination evaluated by AUC and internally validated via bootstrap resampling (2000 iterations). Fifty patients were reviewed. CAV developed in 13 (26%) patients in 3 years. CAV+ patients had a significantly higher ΔAge at discharge compared to CAV- patients (median −1.0 vs. −11.0 years, p = 0.0023) and at 1 year (median +7.0 vs. −4.0 years, p = 0.0080). On univariate analysis, ΔAge at discharge was a significant predictor of the development of CAV (OR 1.084 per year, AUC 0.788). On multivariable adjustment, ΔAge at discharge remained an independent predictor (adjusted OR 1.138, 95% CI 1.023–1.265, p = 0.018, and model AUC 0.859). ΔAge at discharge is a novel and potential predictor of the development of CAV within 3 years. These findings support the integration of AI-ECG into post-transplant surveillance as a scalable, low-cost tool.

Abstract Purpose Validate the semiquantitative (SQ)-MRI score for chronic pancreatitis (CP) diagnosis in an independent, multicenter cohort. Methods We analyzed MRIs performed at baseline in 337 participants with acute (AP) or recurrent AP (RAP) and 67 with non-calcific chronic pancreatitis (NCCP) enrolled in the PROCEED study from 6/2017 to 3/2023. MRIs were performed at multiple clinical centers using site-specific clinical protocols and a variety of MRI vendors to evaluate the SQ-MRI score in a real-world setting. The SQ-MRI score was calculated using the T1 signal intensity ratio of the pancreas to the spleen (T1 score), arteriovenous enhancement ratio (AVR), and pancreatic body diameter (PBD). We adjusted for confounding by participant characteristics via propensity score weighting. Results Median AVR was higher in AP/RAP (1.18, IQR: 0.97–1.44) than in the NCCP group (1.03, IQR: 0.78–1.22, p = 0.007). Pancreatic body diameters were larger in AP/RAP than in the NCCP group − 7–14 mm (10% vs 25%), 14–20 mm (40% vs 54%), and > 20 mm (50% vs 21%), respectively ( p < 0.01). Median T1 score was higher in AP/RAP (1.18, IQR: 0.96–1.40) than in the NCCP group (1.04, IQR: 0.86–1.32, p = 0.10). Median SQ-MRI score in the AP/RAP group was significantly lower, 1.91 (IQR: 0.97, 2.95), than in the NCCP group, 2.74 (IQR: 2.04–4.03) ( p < 0.001). The propensity score-adjusted AUC for SQ-MRI to distinguish AP/RAP from NCCP was 0.64, which was higher than for individual parameters. Conclusion We have validated the SQ-MRI score in a multicenter cohort using an independent, real-world MRI dataset.

Lay Summary Glioblastoma is an aggressive brain cancer, and it can be difficult to tell whether changes seen on scans after radiation treatment represent tumor growth or treatment-related effects. The authors of this study wanted to evaluate whether a specialized imaging test called PSMA PET could help define tumor boundaries for radiation planning and distinguish tumor progression from treatment-related changes. To do this, they performed PSMA PET scans in 27 patients with high-grade gliomas, including patients undergoing radiation planning and patients being evaluated for possible tumor recurrence. They found that tumors showed higher PSMA PET signal than surrounding tissue, that PSMA PET sometimes identified tumor beyond what was visible on standard MRI, and that it correctly distinguished tumor progression from treatment-related changes in most patients.

Importance Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C–related burden is critical for guiding prevention and treatment strategies. Objectives To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends. Design, Setting, and Population This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals. Exposure Population-level LDL-C concentrations. Main Outcomes and Measures Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C–attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals. Results In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C–attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings. Conclusions and Relevance Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.

Introduction Community-acquired pneumonia (CAP) is common and remains the leading infectious cause of death worldwide. Antibiotics remain the mainstay of treatment, but organisms are often not identified, necessitating empirical treatment. Current treatment guidelines recommend combination therapy with beta-lactams and macrolides or monotherapy with fluoroquinolones for non-severe CAP. However, rising antibiotic resistance and safety concerns have led to increased doxycycline use, despite limited evidence supporting its efficacy. Our goal is to conduct a pragmatic, open-label, randomised clinical trial comparing the effectiveness of azithromycin with that of doxycycline in combination with beta-lactam therapy in adult patients hospitalised for CAP. Methods and analysis Patients presenting to the emergency department or directly referred to the hospital with a clinical presentation concerning for CAP and need for hospitalisation are eligible. We plan to enrol 1120 adults hospitalised at six hospitals across four states, including rural, suburban and urban settings and academic and community hospitals. Randomisation will be 1:1 using an electronic health record (EHR)-embedded screening and randomisation tool triggered by the treating clinician’s orders for azithromycin or doxycycline. Outcomes will be ascertained pragmatically via EHR-based data retrieval and will not require additional study visits. Our primary outcome is days alive and out of the hospital through day 28. Secondary outcomes include oxygen-free days; a composite of a need for advanced respiratory support or in-hospital mortality with analyses of each component separately; an ordinal measure of clinical deterioration defined by a prespecified severity scale; and 60-day and 180-day mortality. Safety outcomes are the incidence of Clostridioides difficile infection and QT prolongation. Analyses will follow an intention-to-treat framework, with per-protocol analyses for sensitivity. The primary endpoint will be compared between groups using a stratified van Elteren test, with supportive analyses using proportional odds regression and analysis of covariance adjusted for key covariates. Ethics and dissemination The Mayo Clinic Institutional Review Board reviewed and approved this protocol with a waiver of written consent, requiring verbal consent to be obtained by the clinician initiating the antibiotics (IRB# 24–0 06 503). Findings will be disseminated through peer-reviewed publications and international conference presentations. Trial registration number NCT07164131 .