Saif Syed

Background: Iron deficiency anemia (IDA) is a prevalent nutritional deficiency linked to immune modulation and allergic conditions. This study investigates the association between IDA and allergic diseases, including atopic dermatitis, asthma, allergic rhinitis, food allergy, and allergic eosinophilia. Objective: To evaluate the association between iron deficiency anemia (IDA) and the prevalence of allergic conditions, including atopic dermatitis, asthma, allergic rhinitis, food allergy, and allergic eosinophilia, using a large nationally representative dataset. Methods: A retrospective, cross-sectional design was employed using data from the National Inpatient Sample (2016–2020). Logistic regression models adjusted for confounders such as payer type, race, socioeconomic status, and hospital characteristics were used to assess associations. Results: Among 32,966,720 patients, 1,247,309 (3.8%) had IDA. After adjustment, IDA was significantly associated with increased odds of allergic conditions: atopic dermatitis (OR = 1.30), asthma (OR = 1.21), allergic rhinitis (OR = 1.21), food allergy (OR = 1.18), and allergic eosinophilia (OR = 1.24). Conclusion: IDA was significantly associated with allergic conditions in this analysis, suggesting that iron status may represent a clinically relevant factor in patients with allergic diseases, as seen in this large national inpatient sample. Future longitudinal studies are needed to clarify causal pathways and develop targeted interventions. Addressing nutritional deficiencies may reduce the burden of allergic diseases and improve health outcomes.

Introduction: Cardiovascular disease (CVD) is a leading cause of non-cancer death among cancer survivors, attributable to cardiotoxic therapies and cardiovascular risk factors. General population risk prediction tools, including ASCVD (Atherosclerotic cardiovascular disease), Framingham’s Score, and PREVENT (Predicting Risk of Cardiovascular Disease EVENTS), lack cancer-specific variables. We evaluated whether these models, even after statistical optimization, could predict cardiovascular mortality in cancer survivors. Methods: Using the National Health and Nutrition Examination Survey (NHANES) 2001–2018, linked with National Death Index (NDI) mortality data, we conducted a retrospective analysis of 634 and 429 cancer survivors, respectively, across model-specific cohorts free of baseline cardiovascular disease. Discrimination was assessed for ASCVD, Framingham Score, and PREVENT using standardized thresholds of 7.5% and 20%, as well as Youden-optimized cutoffs. Area under the curve (AUC) comparisons were performed using the DeLong non-parametric method. Results: Standard thresholds showed suboptimal discrimination across all models (AUCs: ASCVD 0.56, Framingham 0.53, PREVENT 0.64). In contrast, Youden-optimized AUCs (ASCVD: 0.68; PREVENT: 0.71; all p < 0.001, DeLong test). Optimization increased the “low-risk” group’s mortality rate from 2.8% to 4.1% (RR = 1.47), suggesting improved statistical fit came at the cost of overestimating the risk. Optimized thresholds outperformed conventional cutoffs, underscoring the necessity for recalibrated, cohort-specific risk stratification in cancer survivors. Conclusions: Standard risk scores have inadequate discrimination for cardiovascular mortality prediction in cancer survivors. Threshold recalibration improves statistical metrics but does not resolve the structural failure of these models to account for cardiotoxic exposure. Development of cardio-oncology-specific risk models incorporating oncologic exposures is therefore warranted.

Abdominal aortic aneurysm (AAA) poses a significant health risk, particularly in aging populations. This study aims to quantify the association between Helicobacter pylori (H. pylori) infection and AAA development through a systematic review and meta-analysis, emphasizing numerical results for clarity. Following PRISMA guidelines, PubMed, SCOPUS, Medline and Embase searches were conducted. Data extraction and quality assessment were performed using standardized tools. Statistical analysis involved calculating a pooled risk ratio (RR) with a 95% confidence interval (CI) to determine the association between H. pylori infection and AAA development. Among the 8 selected studies, H. pylori infection exhibited a statistically significant overall RR of 1.54 (95% CI: 1.14–2.08, P = 0.005) for AAA development. Subgroup and sensitivity analyses were conducted to address high heterogeneity, revealing consistent results. The event rate analysis across studies showed an overall rate of 41%, (95% CI: 0.293 to 0.547) with significant variability observed among individual study populations. The meta-analysis confirms a significant association between H. pylori infection and AAA development, with an elevated risk ratio of 1.54. These findings underscore the importance of further research to elucidate underlying mechanisms and inform preventive strategies and interventions aimed at mitigating the risk of AAA in individuals with H. pylori infection.

Myeloproliferative neoplasms (MPNs) are clonal disorders of hematopoietic stem cells characterized by aberrant proliferation of myeloid lineages, driven primarily by mutations in JAK2, CALR, and myeloproliferative leukemia, leading to constitutive activation of the JAK-STAT pathway. Emerging evidence highlights mitochondrial dysfunction as a key factor in MPN pathogenesis, contributing to increased reactive oxygen species production, mitochondrial DNA mutations, and dysregulated mitochondrial dynamics, which collectively promote clonal expansion and apoptosis resistance. Targeting mitochondrial pathways has gained attention as a therapeutic strategy, with approaches including mitochondria-targeted antioxidants, metabolic inhibitors, and modulation of mitophagy and mitochondrial fission/fusion dynamics. However, challenges such as drug delivery specificity, therapeutic resistance, and off-target effects remain significant. Recent advances in precision medicine, incorporating genomic, transcriptomic, and proteomic profiling, offer a more personalized approach to MPN treatment by tailoring interventions to individual mutation patterns. Additionally, novel therapeutic strategies, including gene editing technologies, RNA-based therapies, and nanoparticle-mediated drug delivery systems, hold promise for overcoming current treatment limitations. The integration of artificial intelligence in drug discovery and biomarker identification further enhances the potential for targeted therapies. Future research should focus on refining these strategies, developing reliable biomarkers for patient stratification, and exploring combination therapies that enhance treatment efficacy while minimizing adverse effects. By addressing mitochondrial dysfunction as an underlying driver of MPNs, these emerging approaches have the potential to improve disease management, extend patient survival, and enhance quality of life. Also, this new approach of precision medicine allows patient stratification and ensures that treatments are formed according to the individual disease biology of each patient, which results in overall better outcomes.

Background/objective: HCM is a structural disorder of the myocardium that leads to sudden cardiac death in young adults. We synthesized an updated understanding of the role of Cardiac Myosin Inhibitors (CMIs) in HCM by pooling data from RCTs. Methods: We identified six published RCTs, involving 826 participants. Data were extracted pertaining to study characteristics; primary outcomes of interest–(1) change from baseline in resting left ventricular outflow tract (LVOT) peak gradient, (2) change from baseline in Valsalva LVOT peak gradient, and (3) improvement of ≥1 NYHA class–and secondary outcomes. These were pooled using Review Manager 5.4, employing a random-effects model, and reported as odds ratios (ORs) or mean differences (MDs). Results: We found statistically significant between-group difference favoring CMIs in change from baseline in LVOT peak gradient: at rest (MD −39.33; −53.01 to −25.64), post-Valsalva (MD −48.99; −53.96 to −44.03), and post-exercise (MD −37.11; −44.34 to −29.87); ≥1 NYHA class improvement (OR 4.10; 2.79–6.02), change from baseline in peak oxygen uptake (MD −37.11; −44.34 to −29.87), LVOT gradient ≤30 mm hg (RR 14.89; 7.47–29.67), participants eligible for septal reduction therapy (RR 0.26; 0.18–0.36), and change from baseline in KCCQ-CSS score (MD 8.54; 5.36–11.71). Subgrouping by intervention type (mavacamten vs. aficamten) revealed non-significant results for all primary outcomes. Conclusions: CMIs can contribute to improving key efficacy outcomes for patients with HCM while reducing incidence of SRT.

Background: Immunotherapy that includes immune checkpoint inhibitors (ICI) is a revolutionary arm of the treatment of skin cancers like melanoma, basal cell carcinoma, and squamous cell carcinoma. Despite this leap in clinical advances, a critically challenging area in this field is emerging resistance to immunotherapy that limits its efficaciousness in a profound segment of the population. This resistance can be classified as primary resistance, in which cancers fail to respond to initial regimen, or acquired resistance that develops after there is a favorable initial response. A comprehensive understanding of the basic mechanisms and figuring out novel strategies to combat resistance are necessary to improve patient outcomes.Methods: A comprehensive review of recent studies was conducted with focus on preclinical and clinical evidence related to immunotherapy resistance in skin cancer with a wide literature search on databases such as PubMed, Cochrane, and Google Scholar with keywords, including “skin cancer,” “immunotherapy,” “malignant melanoma,” “drug resistance,” “mechanisms,” and “strategies” published in the last 15 years.Results: This study aims to establish a review of the molecular and cellular mechanisms that contribute to development of drug resistance in skin cancer and to gauge emerging strategies to overcome these barriers. Insights into these mechanisms were classified into tumor‐intrinsic factors, like genetic and epigenetic changes, and tumor‐extrinsic factors, such as changes in tumor microenvironment (TME) and systemic immunosuppression. Therapeutic strategies that included combination therapies, newer checkpoint inhibitors, and modulation of the TME were evaluated. Key mechanisms leading to drug resistance identified include tumor‐intrinsic factors, including mutations in signaling pathways, tumor‐extrinsic factors, including immunosuppressive cells and changes in the TME, such as hypoxia that contributed to drug resistance. Upcoming strategies to counteract resistance included combination approaches, adoptive T‐cell therapy, and newer immunomodulatory agents that target resistance pathways.Conclusions: There is a complex interplay of cancer and immune microenvironmental mechanisms that leads to development of immunotherapy resistance in skin tumor patients. A multi‐pronged approach with focus in fields of genomics and immunology as well as bioinformatics is required, along with combination therapies and novel immunomodulators, to tackle resistance and enhance clinical outcomes for patients suffering with skin tumors.

Objective: To find out the efficacy of Inclisiran sodium in heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH) patient groups. Methods: PubMed, Embase, and Clinicaltrials.gov databases were searched for the relevant studies. Atherosclerotic parameters considered included LDL-C, total cholesterol, PCSK9, apolipoprotein-B, and non-HDL-C. Primary outcomes were the percentage difference in atherosclerotic parameters at follow-up relative to baseline values. Our study examined these primary outcomes to determine whether there is a statistically significant difference between the HeFH and HoFH groups. The risk of bias was assessed by the Cochrane risk of bias tool. Results: Analysis of four ORION clinical trials unveiled the significant difference in pooled mean differences in LDL-C (HeFH: –48.62%, HoFH: –9.12%; P < 0.05) total cholesterol (HeFH: –30.31%, HoFH: –11.50%; P < 0.05), apolipoprotein-B (HeFH: –39.97%, HoFH: –14.68%, P < 0.05), and non-HDL-C (HeFH: –44.51%, HoFH: –12.22%; P P = 0.2) between the HeFH and HoFH groups was statistically insignificant. Studies were of high quality. Conclusion: There was a significant difference in the reductions in atherosclerotic lipid parameters in heterozygous and homozygous populations after the administration of inclisiran except for the PCSK9 parameter. Further studies are needed to support this conclusion.

Colorectal cancer (CRC) is a common malignancy with high incidence and mortality. Hormone signaling pathways, including estrogen, progesterone (P4), and androgen receptors (ARs), influence tumor development and progression and offer potential therapeutic opportunities. This study investigates the role of sex steroid receptors in CRC, explores therapeutic strategies, and considers sex-specific implications. Multiple cohort studies were analyzed based on gender, age, clinical stage, and tumor location. A structured literature search was conducted across PubMed, Web of Science, and Google Scholar, selecting studies with relevant sex-specific data and study designs. ERβ exhibits antitumor effects, with lower levels linked to tumors in females, while ERα and AR promote growth, particularly in postmenopausal women. Progesterone receptors (PGRs) are associated with poorer prognosis, though P4 treatment inhibits CRC cell proliferation. Malignant tissues show increased ERα and AR but decreased ERβ and PGR. ER isoforms’ mRNA is lower in malignant females, and AR expression is higher in males. Women more often develop proximal colon tumors (reduced ERβ) and men develop distal tumors, reflecting nuanced gene transcription modulation by ERα, ERβ, and G-protein coupled estrogen receptor (GPER). The mechanism of P4’s protective effect remains unclear. Variability in cell lines, hormone concentrations, receptor expression, and hormone replacement therapy outcomes complicates interpretation, as do interactions between cytokines and estrogen signaling in the tumor microenvironment. Future strategies include combined ERβ and PGR activation, sequential estrogen-P4 therapy for early stage CRC, and simultaneous therapy for advanced cases. Research should clarify sex hormone roles, advance prognostic markers, explore selective estrogen receptor modulators, target ERβ pharmacologically, and investigate gut microbiome influences for tailored interventions.

Diabetes mellitus (DM) is a long-term metabolic disorder caused by inadequate production and resistance to insulin. The prevalence of DM is rapidly increasing, with type 2 diabetes (T2D) accounting for more than 90% of cases. Despite new treatments, many patients with T2D do not meet their glycemic targets due to clinical inertia. This review provides an overview of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in the management of T2D. The review synthesizes data from clinical trials and meta-analyses on the efficacy, safety, and cost-effectiveness of GLP-1 RAs. It also discusses the mechanisms of action, classification, and barriers to adherence and persistence in therapy. GLP-1 RAs improve glycemic control by lowering A1C levels and promoting weight loss. They have cardioprotective effects and may reduce endothelial inflammation, oxidative stress, and blood pressure. Adherence to GLP-1 RAs is better with once-weekly injections, though gastrointestinal side effects and cost can affect persistence. Semaglutide and liraglutide have shown significant weight reduction, with semaglutide being particularly effective. GLP-1 RAs are cost-effective due to reduced healthcare costs associated with fewer hospitalizations and lower mortality rates. Safety concerns include gastrointestinal issues, pancreatitis, and rare cases of diabetic retinopathy and thyroid C-cell tumors. For clinical practice, GLP-1 RAs represent a valuable option not only for glycemic control but also for weight management and cardiovascular protection. Incorporating GLP-1 RAs into treatment plans can improve patient outcomes, and optimizing dosing regimens and addressing barriers such as cost and side effects are crucial to enhancing patient adherence and long-term treatment success.

The possible cardiovascular advantages of glucagon-like peptide-1 receptor agonists (GLP-1RAs), a class of drugs predominantly used to treat type 2 diabetes (T2D), have garnered increasing attention in recent years. Clinical trials have looked into the possibility that GLP-1RAs have extra cardioprotective benefits in addition to their ability to manage T2D, demonstrating significant major adverse cardiovascular events (MACE) reduction and a favorable safety profile. GLP-1 RAs improve cardiovascular outcomes, especially in those with existing cardiovascular disease. MACE has been steadily declining with this class of drugs, which results in a noticeable rise in cardiovascular outcome trials (CVOTs). GLP-1 RAs have a variety of impacts on the cardiovascular system beyond their function in glycemic control. They offer direct cardioprotection, vasodilation, promotion of salt excretion, reduction of weight, improved lipid profile, and anti-inflammatory qualities through a variety of mechanisms. Thus, this review focuses on GLP-1RAs, its mechanism of action, its clinical effectiveness in CVOTs, the mechanism behind its cardiovascular benefits, its potential role in heart failure, cardiovascular outcomes, its underutilization, and future directives. In conclusion, GLP-1 RAs shows potential in controlling T2D while also lowering cardiovascular risk, but warrants further study into long-term results and real-world data to optimize treatment regimens, ultimately increasing patient outcomes and lowering the burden of cardiovascular disease in T2D populations.