Muhammad Nabeel Saddique

Background and Aims: Diabetes mellitus (DM) is a major global health concern, particularly in resource‐constrained settings. Incarcerated populations in low‐ and middle‐income countries (LMICs) face increased health risks and limited care access, yet remain understudied. No prior systematic review has synthesized prevalence data for this group. This review aims to estimate diabetes prevalence among incarcerated individuals in LMICs. Methods: We conducted a systematic review and meta‐analysis per PRISMA and GATHER guidelines. PubMed, Scopus, Embase, Web of Science and regional databases were searched till May 2025. Random‐effects models with Freeman‐Tukey double arcsine transformation were applied in R (version 4.5.1). Publication bias was assessed using DOI plots. Study quality was evaluated with the Joanna Briggs Institute tool, and certainty of evidence was appraised using an adapted GRADE approach. Results: Twenty‐three studies (107,473 participants) were included. Mean participant ages varied from 29 ± 9.6 to 40.5 ± 9.8 years. The tentative pooled estimate of diabetes prevalence was 3.7% (95% CI: [2.5%–5.1%], Prediction Interval [0%–12.2%]), with high heterogeneity ( I ² = 95.4%). The pooled prevalence estimate was highest in Asia (5.2%), particularly Pakistan (9.8%), and lowest in South America (2.3%). The DOI plot revealed major asymmetry, indicating a high possibility of publication bias. Overall certainty of evidence was rated as very low for diabetes prevalence due to risk of bias and publication bias. Interpretation of the pooled estimate is limited by substantial heterogeneity and limitations in the primary studies, including differences in diabetes ascertainment methods. Conclusion: Diabetes is an important health concern among incarcerated populations in LMICs. Differences in diabetes ascertainment methods, participant characteristics and correctional healthcare systems may have potentially contributed to the variability of the pooled estimates. A hypothesis is that there may also be potentially limited detection or underdiagnosis which possibly could have contributed to the observed prevalence estimates.

Background: Acute coronary syndrome (ACS) remains a major contributor to global mortality and long-term cardiovascular risk despite optimal treatment. Colchicine, an anti-inflammatory agent, has gained attention for its potential benefits in ACS. This meta-analysis evaluates its safety and impact on major adverse cardiovascular events (MACE), high-sensitivity C-reactive protein (hsCRP) levels, and cardiac function in ACS patients. Methods: We performed a systematic literature search of randomized controlled trials on PubMed (MEDLINE), Embase, and Scopus databases from inception to January 1st, 2025. We pooled dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean differences (MD) with 95% confidence intervals, using random-effects models. Heterogeneity was assessed using I2 and X2 statistics. Statistical significance was defined by a p-value <0.05. Analyses were performed with RevMan 5.4. Results: The meta-analysis included 18 RCTs involving 14,688 patients (7,336 receiving colchicine and 7,352 controls). 11,742 (79.94%) were men and mean age was 59.8±8.8 years. Compared to placebo, colchicine reduced the rate of MACE (RR=0.74, 95%CI:0.60 to 0.92), even when examined after 1 or more years of therapy (RR 0.83, 95%CI:0.70 to 0.98), reduced hsCRP levels (MD -0.80, 95%CI:-1.34 to -0.27), and improved left ventricular ejection fraction (MD 1.13, 95%CI:0.25 to 2.02]). While no increase in overall adverse events was seen with colchicine (RR 1.00, 95% CI: 0.95 to 1.06), diarrhea occurred more frequently (RR=1.52, 95%CI: 1.03 to 2.24). Conclusion: Colchicine appears safe and may improve long-term outcomes in ACS patients. However, larger studies with more extended follow-up are needed for definitive evidence.

Kaposi sarcoma (KS) is a multifocal angioproliferative disorder closely linked to human herpesvirus-8 (HHV-8) infection and profound immunodeficiency. Despite landmark advances in combination antiretroviral therapy (cART) that have lowered KS incidence, this malignancy persists as a significant cause of morbidity and mortality, particularly in sub-Saharan Africa and among marginalized populations. Here, we review the current understanding of KS pathogenesis, emphasizing the interplay between viral latency, lytic reactivation, and host immune suppression. We summarize epidemiological trends before and after cART implementation, highlighting regional disparities in seroprevalence and cancer burden. Key challenges in KS management include delayed diagnosis due to lesion heterogeneity, difficulty distinguishing KS from mimickers such as bacillary angiomatosis, and barriers to histopathological confirmation in resource-limited settings. We evaluate therapeutic approaches, from early antiretroviral therapy (ART) initiation and supportive chemotherapy to novel targeted agents like pomalidomide and immune checkpoint inhibitors, and discuss their limitations and emerging prospects. Future directions focus on HHV-8 vaccine development, implementation of point-of-care diagnostics enhanced by artificial intelligence, and integration of KS surveillance into existing HIV frameworks. Comprehensive prevention strategies encompassing routine HHV-8 screening of high-risk groups, robust adherence support for ART, and interdisciplinary care models are essential to curb KS’s global impact. Bridging research, clinical practice, and public health efforts will be critical to achieving equitable access to early detection and innovative treatments, thereby transforming KS from a relentless complication of HIV to a manageable condition.

Introduction Aortic stenosis (AS) and hypertension (HTN) frequently co-exist in older adults, worsening disease progression and increasing mortality risk compared to either condition alone. Aim To examine mortality trends and demographic-geographic disparities from comorbid AS and HTN in the U.S. from 1999–2020. Methods Data were extracted from the CDC WONDER Multiple Cause of Death database. Crude and age-adjusted mortality rates (CMRs, AAMRs) per 100,000 were calculated. Joinpoint regression estimated annual (APC) and average annual percent change (AAPC). Trends were projected to 2030 using an autoregressive integrated moving average (ARIMA) model. Results Between 1999 and 2020, 100,507 deaths were attributed to comorbid AS and HTN. The overall AAMR significantly increased (AAPC: 5.01%), with a steep rise from 1999–2001 (APC: 21.95%) and consistent increase from 2001–2020 (APC: 3.46%). AAMRs were higher in men (11.6) than women (10.1). NH Whites had the highest AAMR (11.4), followed by Hispanic/Latino and NH Black (7.4), and NH Asian/Pacific Islanders (6.2). AAMRs also varied by region (West: 13.5; Midwest: 11.5; Northeast: 10.7; South: 8.6). Most deaths occurred in medical facilities (34.4%) or at home (31.5%). Vermont, Minnesota, New Hampshire, California, and Nebraska had the highest AAMRs. Non-metropolitan areas had higher AAMRs than metropolitan (11.4 vs. 10.6). Adults ≥ 85 years had the highest CMR (53.6). ARIMA projected AAMR to reach 25.4 by 2030 (22.0 in females, 28.3 in males). Conclusion Mortality from concurrent AS and HTN is rising, with notable demographic and geographic disparities. Early detection, integrated care, and targeted public health strategies are critical. Graphical Abstract The alternative text for this image may have been generated using AI.

Non–small cell lung cancer (NSCLC) accounts for the majority of lung cancer cases and remains a leading cause of cancer mortality worldwide. Pathophysiologically, NSCLC arises from genetic alterations such as EGFR, KRAS, and ALK mutations, which drive dysregulated signaling, uncontrolled proliferation, and immune evasion. Standard treatments include surgery, radiotherapy, platinum-based chemotherapy, and immunotherapy with PD-1/PD-L1 inhibitors, yet survival outcomes remain suboptimal. Emerging evidence suggests that circadian biology influences therapeutic efficacy, with time-of-day (ToD) immunochemotherapy offering a novel approach to optimize outcomes. Mechanistically, circadian rhythms regulate immune cell trafficking, cytokine release, and drug metabolism, thereby modulating treatment response and toxicity. Clinical trials in NSCLC demonstrate that early-day administration of immunochemotherapy improves progression-free and overall survival compared to late dosing. Similar chronotherapy benefits have been reported in colorectal, breast, pancreatic, and hepatocellular cancers, underscoring broad translational relevance. Despite promise, challenges include patient heterogeneity in circadian rhythms, logistical barriers in oncology clinics, and limited biomarker validation. Future strategies should prioritize multicenter validation, integration of chronobiological profiling, and exploration of combination therapies. Cost-effectiveness analyses, awareness campaigns, and clinical drives to evaluate safety and adherence will be essential to establish trust and optimize outcomes.

Thrombocytopenia, a common side effect of chronic liver disease (CLD), increases bleeding risk during invasive procedures. Thrombopoietin receptor agonists (TPO-RAs) offer an effective alternative to platelet transfusions. A systematic review and meta-analysis assessed the efficacy and safety of TPO-RAs in thrombocytopenia patients undergoing elective procedures. A systematic search (PubMed, Google Scholar, Cochrane Library, up to August 2024) evaluated perioperative thrombopoietin receptor agonists in patients with thrombocytopenia undergoing elective procedures. Primary and secondary outcomes included platelet count ≥50 x 10^9/L, bleeding/thrombotic events, platelet transfusions, adverse effects, rescue treatment, discontinuation, death, and serious adverse effects, analyzed via random-effects model. This meta-analysis synthesized evidence from nine trials and 1,409 patients (819 TPO-RAs vs 590 placebo; mean age ~59 years). TPO-RAs significantly increased the likelihood of achieving platelet counts ≥50×10⁹/L compared with placebo (RR 3.93, 95% CI 2.24–6.90; p<0.00001). They also reduced the need for preoperative platelet transfusions (RR 0.34, 95% CI 0.27–0.44; p<0.00001) and lowered the risk of surgical bleeding (RR 0.64, 95% CI 0.49–0.85; p=0.002). In contrast, no statistically significant differences were observed for thrombotic events (RR 1.24, 95% CI 0.57–2.67; p=0.59), treatment-emergent adverse events (RR 0.99, 95% CI 0.89–1.09; p=0.83), study drug discontinuation (RR 0.74, 95% CI 0.32–1.70; p=0.47), rescue treatment use (RR 0.82, 95% CI 0.34–2.03; p=0.67), all-cause mortality (RR 1.23, 95% CI 0.35–4.35; p=0.75), or serious adverse events (RR 1.13, 95% CI 0.70–1.84; p=0.62). TPO-RAs raise platelet counts and reduce transfusions in CLD patients undergoing invasive procedures. However, close monitoring for thrombotic risks is necessary, and further research is needed to optimize dosing. Graphical Abstract

The mcr gene family, responsible for plasmid-mediated resistance to colistin, poses a growing threat to public health by reducing the efficacy of colistin, a critical last-resort antibiotic for multidrug-resistant Gram-negative bacteria. The mcr-1 gene, discovered in 2015, marked a significant shift in understanding colistin resistance, and subsequent mcr variants (mcr-2 to mcr-10) have emerged globally. These genes alter lipid A in bacterial cell membranes, decreasing colistin’s binding and efficacy. The mcr genes are typically located on mobile plasmids, facilitating horizontal gene transfer across bacterial species. Our review examines the evolution, genetic mechanisms, and structural characteristics of the mcr gene family, discussing their spread across human, animal, and environmental contexts. In this review, we highlight the clinical implications of mcr-mediated resistance, noting the co-occurrence of mcr with other antimicrobial resistance determinants, which complicates treatment options. Additionally, it explores detection methods, global epidemiology, and potential strategies to combat mcr resistance, including the development of inhibitors and CRISPR-based gene editing. Our review concludes that combating mcr-mediated colistin resistance requires global surveillance, coordination across sectors, and continued research to stop its spread and impact.