Evaluating the Efficacy of Antioxidant Therapy in Enhancing the Quality of Life of Chronic Pancreatitis Patients: A Systematic Review.

Chronic pancreatitis (CP), an inflammatory disease characterized by irreversible pancreatic changes and progressive fibrosis, significantly impairs patients' quality of life. This systematic review aims to assess the efficacy of antioxidant therapy in enhancing the quality of life of CP patients. Focusing on the role of oxidative stress in CP pathogenesis, we explored several databases for studies evaluating the impact of antioxidant supplementation. The review included randomized controlled trials and cohort studies reporting pain frequency, intensity, and overall quality of life measures. Findings from these studies present a mixed view of the efficacy of antioxidants in CP, with some suggesting benefits in symptom management, while others show inconsistency in improving patient outcomes. The review concludes that while antioxidant therapy holds potential, especially in symptom alleviation, there is a need for more rigorous, larger-scale studies to confirm its effectiveness in CP management and to establish standardized treatment protocols. The incorporation of antioxidants into CP treatment plans should be approached with personalized care, considering the varied responses observed in different patient populations.

Unraveling the Enigma of Aortic Dissection: From Genetics to Innovative Therapies.

Aortic dissection (AD) presents a critical medical emergency characterized by a tear in the aortic wall, necessitating prompt recognition and management to mitigate catastrophic complications. Despite advancements in medical technology and therapeutic interventions, AD remains a formidable challenge, often resulting in severe morbidity and mortality. This narrative review provides a comprehensive overview of AD, encompassing its clinical presentation, diagnostic modalities, and management strategies, while also exploring emerging trends and innovations in its management. Genetic predispositions significantly influence AD pathogenesis, with over 30 contributory genes identified, emphasizing the importance of genetic screening and counseling. Classification systems such as Stanford and DeBakey, alongside their revised counterparts, aid in categorizing AD and guiding treatment decisions. Advancements in diagnostic imaging, including transesophageal echocardiography and computed tomography angiography, have enhanced diagnostic precision, augmented by artificial intelligence and machine learning algorithms. Pharmacological innovations focus on optimizing medical therapy, while surgical and endovascular approaches offer minimally invasive treatment options. Hybrid procedures and aortic valve-sparing techniques broaden treatment avenues, while bioresorbable stent grafts hold promise for tissue regeneration. Collaborative efforts and ongoing research are essential to address remaining challenges and improve outcomes in managing AD. This review contributes to the understanding of AD's complexity and facilitates informed decision-making in clinical practice, underscoring the imperative for continued innovation and research in AD management.

The Potential of Fecal and Urinary Biomarkers for Early Detection of Pancreatic Ductal Adenocarcinoma: A Systematic Review.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer often diagnosed at advanced stages, highlighting the urgent need for early detection strategies. This systematic review explores the potential of fecal and urinary biomarkers for early PDAC detection. A comprehensive search identified eight relevant studies investigating various biomarkers, including proteins, metabolites, microbial profiles, DNA mutations, and non-coding RNAs. Promising findings suggest that urinary biomarkers related to metabolic alterations, inflammatory processes, fecal microbiome profiles, and fecal miRNAs hold diagnostic potential even at early stages of PDAC. Combining biomarkers into panels may enhance diagnostic accuracy. Challenges such as validation in larger cohorts, standardization of protocols, and regulatory approval must be addressed for clinical translation. Despite these hurdles, non-invasive urinary and fecal biomarkers represent a promising avenue for improving PDAC outcomes through early detection.

Ion transporter cascade, reactive astrogliosis and cerebrovascular diseases.

Cerebrovascular diseases and their sequalae, such as ischemic stroke, chronic cerebral hypoperfusion, and vascular dementia are significant contributors to adult disability and cognitive impairment in the modern world. Astrocytes are an integral part of the neurovascular unit in the CNS and play a pivotal role in CNS homeostasis, including ionic and pH balance, neurotransmission, cerebral blood flow, and metabolism. Astrocytes respond to cerebral insults, inflammation, and diseases through unique molecular, morphological, and functional changes, collectively known as reactive astrogliosis. The function of reactive astrocytes has been a subject of debate. Initially, astrocytes were thought to primarily play a supportive role in maintaining the structure and function of the nervous system. However, recent studies suggest that reactive astrocytes may have both beneficial and detrimental effects. For example, in chronic cerebral hypoperfusion, reactive astrocytes can cause oligodendrocyte death and demyelination. In this review, we will summarize the (1) roles of ion transporter cascade in reactive astrogliosis, (2) role of reactive astrocytes in vascular dementia and related dementias, and (3) potential therapeutic approaches for dementing disorders targeting reactive astrocytes. Understanding the relationship between ion transporter cascade, reactive astrogliosis, and cerebrovascular diseases may reveal mechanisms and targets for the development of therapies for brain diseases associated with reactive astrogliosis.

From Sugar Spikes to Pressure Peaks: Navigating the World of Diabetes, Hypertension, Obesity, and Kidney Health.

Diabetes, hypertension, obesity, and chronic kidney disease (CKD) are major public health challenges globally, contributing significantly to morbidity and mortality. The co-occurrence and interplay among these conditions exacerbate health outcomes, highlighting the need for an integrated understanding and approach to management. This narrative review aims to explore the complex relationships between diabetes, hypertension, obesity, and CKD, elucidating their collective impact on health. It discusses the epidemiological trends, underlying pathophysiological mechanisms, genetic predispositions, current treatment strategies, and the future direction of research and therapy. An extensive review of current literature was conducted, focusing on the epidemiology, pathophysiology, risk factors, diagnosis, and treatment of diabetes, hypertension, obesity, and CKD. Additionally, the review delves into the genetic and molecular biology underlying these conditions, the potential for personalized medicine, and the importance of a multidisciplinary approach to care. The review identifies key areas where these conditions intersect, enhancing disease progression and complicating management. It highlights the role of genetic and environmental factors in disease etiology, the critical need for personalized treatment strategies, and the gaps in current management approaches. Innovations in pharmacotherapy, monitoring technologies, and the potential of pharmacogenomics are discussed as avenues for advancing patient care. Diabetes, hypertension, obesity, and CKD are intricately linked, necessitating an integrated, patient-centered approach to care that goes beyond traditional treatment modalities. Future research should focus on collaborative models and interdisciplinary strategies to address the multifaceted challenges posed by these conditions. Emphasizing personalized medicine and leveraging technological advancements offer promising pathways to improve outcomes and reduce the global health burden of these metabolic disorders.

SPAK inhibitor ZT-1a attenuates reactive astrogliosis and oligodendrocyte degeneration in a mouse model of vascular dementia.

BACKGROUND: Astrogliosis and white matter lesions (WML) are key characteristics of vascular contributions to cognitive impairment and dementia (VCID). However, the molecular mechanisms underlying VCID remain poorly understood. Stimulation of Na-K-Cl cotransport 1 (NKCC1) and its upstream kinases WNK (with no lysine) and SPAK (the STE20/SPS1-related proline/alanine-rich kinase) play a role in astrocytic intracellular Na+ overload, hypertrophy, and swelling. Therefore, in this study, we assessed the effect of SPAK inhibitor ZT-1a on pathogenesis and cognitive function in a mouse model of VCID induced by bilateral carotid artery stenosis (BCAS). METHODS: Following sham or BCAS surgery, mice were randomly assigned to receive either vehicle (DMSO) or SPAK inhibitor ZT-1a treatment regimen (days 14-35 post-surgery). Mice were then evaluated for cognitive functions by Morris water maze, WML by ex vivo MRI-DTI analysis, and astrogliosis/demyelination by immunofluorescence and immunoblotting. RESULTS: Compared to sham control mice, BCAS-Veh mice exhibited chronic cerebral hypoperfusion and memory impairments, accompanied by significant MRI DTI-detected WML and oligodendrocyte (OL) death. Increased activation of WNK-SPAK-NKCC1-signaling proteins was detected in white matter tissues and in C3d+ GFAP+ cytotoxic astrocytes but not in S100A10+ GFAP+ homeostatic astrocytes in BCAS-Veh mice. In contrast, ZT-1a-treated BCAS mice displayed reduced expression and phosphorylation of NKCC1, decreased astrogliosis, OL death, and WML, along with improved memory functions. CONCLUSION: BCAS-induced upregulation of WNK-SPAK-NKCC1 signaling contributes to white matter-reactive astrogliosis, OL death, and memory impairment. Pharmacological inhibition of the SPAK activity has therapeutic potential for alleviating pathogenesis and memory impairment in VCID.

Sertraline versus escitalopram in South Asians with moderate to severe major depressive disorder: (SOUTH-DEP) a double-blind, parallel, randomized controlled trial.

Objective: The study design included the double-blind, parallel, randomized controlled trial. The aim of this randomized controlled trial was to compare the efficacy and safety of sertraline and escitalopram in participants with moderate to severe major depressive disorder (MDD). Methods: The study was conducted in South Asian participants. A total of 744 participants with moderate to severe MDD were randomly assigned to receive either sertraline or escitalopram for 8 weeks. Drug dosages and titration schedules were based on the recommendations of the prescribing information for each product and according to the judgment of the clinicians involved in the study. The primary outcome measures were changes from baseline on the Montgomery-Åsberg Depression Rating Scale (MADRS) and the clinical global impression (CGI) scale as well as the frequency of adverse events in both groups. Baseline MADRS scores in the escitalopram and sertraline groups were 28.2±0.47 (mean±SD) and 29.70±0.46 (mean±SD) respectively, and was no variability in the baseline assessments. Changes in MADRS as well as CGI scales at the end of the study were significant only for the sertraline group whereas they remained statistically nonsignificant for the escitalopram group. Results: The results of the study showed that sertraline was more efficacious than escitalopram in reducing depression rating scales such as MADRS and CGI, and that participants subjectively felt better regarding their symptoms in the sertraline group. Sertraline displays enhanced safety or tolerability than other groups of antidepressants, which frequently cause high levels of drowsiness, dizziness, blurred vision, and other undesirable effects. Adverse events were seen in both groups, but delayed ejaculation was the most frequent adverse event seen in both groups. However, a greater number of participants reported having nausea and insomnia in the sertraline group compared to the escitalopram group. Conclusion: Our study clearly highlights that there is a statistically significant difference in efficacy between sertraline and escitalopram at the doses used in our study. Sertraline was able to significantly lower the depression rating scales like MADRS and CGI in participants with moderate to severe MDD. Participants subjectively felt better regarding their symptoms in the sertraline group. The most frequent adverse event in both groups was delayed ejaculation. From an efficacy standpoint, sertraline was more efficacious than escitalopram. The study indicates that the prevalence of depressive disorders in South Asia is comparable to the global estimate, and Bangladesh and India has higher proportions of people with depressive disorders in South Asia. Additionally, females and older adults (75-79 years) have the highest burden of depressive disorders across all countries in the region. This study's limitation included the absence of a placebo arm. An additional limitation of the current study was the lack of an evaluation of inter-rater reliability and the research sample could not have been uniform in terms of the kind of depressive disorders and bipolarity.

Effect of Caffeine in Hypertension.

Hypertension (HTN) is characterized by an elevated arterial blood pressure with no apparent symptom while proving to be a crucial risk factor for the other underlying disorders such as cardiac failure, atrial fibrillation, stroke and various others, steering to recurrent premature deaths worldwide if left untreated. There are innumerate factors responsible for causing HTN such as age factor, obesity, inheritance, physical inactivity, stress, and unhealthy diet whereas some therapeutics and pharmaceuticals may too trigger this condition notably caffeine. As caffeine is amongst the most widely consumed drinks worldwide and hence an ordeal to cease its use, accordingly this review article in-sighted to raise cognizance specifically towards the action of caffeine affiliated with HTN. Therefore, this review is focused on the risk factors and preventive measures associated with HTN, especially the role of caffeine in inducing HTN as to create social awareness regarding how the excessive habituated caffeine consumption may aggravate this condition.

Comparative Efficacy and Safety Profiles of High-power, Short-duration and Low-power, Long-duration Radiofrequency Ablation in Atrial Fibrillation: A Systematic Review and Meta-analysis.

High-power, short-duration (HPSD) radiofrequency (RF) ablation is expected to be more effective and safer than low-power, long-duration (LPLD) RF ablation in treating atrial fibrillation (AF). Given the limited data available, the findings are controversial. This meta-analysis evaluated whether the clinical effects of HPSD outweigh those of LPLD. A systematic search of PubMed, Embase, and Google Scholar databases identified studies comparing HPSD to LPLD ablation. All the analyses used the random-effects model. This analysis included 21 studies with a total of 4,169 patients. Pooled analyses revealed that HPSD was associated with a lower recurrence of atrial tachyarrhythmias (ATAs) at 1 year (relative risk [RR], 0.62; 95% confidence interval [CI], 0.50-0.78; P = .00001; I2 = 0%). Furthermore, the HPSD approach reduced the risk of AF recurrence (RR, 0.64; 95% CI, 0.40-1.01; P = .06; I2 = 86%). The HPSD approach was associated with a lower risk of esophageal thermal injury (ETI) (RR, 0.78; 95% CI, 0.58-1.04; P = .09; I2 = 73%). The HPSD strategy increased first-pass pulmonary vein (PV) isolation (PVI) and decreased acute PV reconnection (PVR), both of which were predominantly manifested in bilateral and left PVs. HPSD facilitated a reduction in procedural time, number of lesions created during PVI, and fluoroscopy time. The HPSD method reduces ETI, PVR, and recurrent AF. The HPSD approach also reduced the procedural time, number of lesions created during PVI, fluoroscopy time, and post-ablation AF relapse in 1 year, improving patient outcomes and safety.

Knowledge, attitudes, and practices of the general population of Pakistan regarding typhoid conjugate vaccine: findings of a cross-sectional study.

Typhoid fever, a common enteric disease in Pakistan, caused by Salmonella typhi, is becoming an extended drug-resistant organism and is preventable through the typhoid conjugate vaccine (TCV). Public adherence to preventive measures is influenced by knowledge and attitude toward the vaccine. This study investigates the knowledge, attitudes, and practices of the general population of Pakistan toward TCV. The differences in mean scores and factors associated with typhoid conjugate vaccine knowledge, attitudes, and practices were investigated. A total of 918 responses were received with a mean age of 25.9 ± 9.6, 51% were women, and 59.6% had graduation-level education. The majority of them responded that vaccines prevent illness (85.3%) and decrease mortality and disability (92.6%), and typhoid could be prevented by vaccination (86.7%). In total, 77.7 and 80.8% considered TCV safe and effective, respectively. Of 389 participants with children, 53.47% had vaccinated children, according to the extended program on immunization (EPI). Higher family income has a higher odds ratio (OR) for willingness toward booster dose of TCV [crude odds ratio (COR) = 4.920, p-value <0.01; adjusted odds ratio (aOR) = 2.853, value of p <0.001], and negative attitude regarding the protective effect of TCV has less willingness toward the booster dose with statistical significance (COR = 0.388, value of p = 0.017; aOR = 0.198, value of p = 0.011). The general population of Pakistan had a good level of knowledge about the benefits of TCV, and attitude and practices are in favor of the usage of TCV. However, a few religious misconceptions are prevalent in public requiring the efforts to overcome them to promote the usage of vaccines to prevent the disease and antibiotic resistance.

Clinical Outcomes of Polymer-Free Versus Polymer-Coated Drug-Eluting Stents in Patients With Coronary Artery Disease: A Systematic Review and Meta-Analysis.

Drug-eluting stents have transformed the treatment of coronary artery disease (CAD), and there are two types: polymer-free and polymer-coated stents. Polymer-free stents have a coating that is quickly absorbed by the body, whereas polymer-coated stents have a coating that remains on the stent surface. This meta-analysis and systematic review aimed to compare the clinical outcomes of these two stent types in patients with coronary artery disease. The literature and abstracts from significant databases were reviewed to compare polymer-free drug-eluting stents (PF-DES) and polymer-coated drug-eluting stents (PC-DES) for the treatment of coronary artery disease (CAD). The primary efficacy endpoints of the study were all-cause mortality and deaths from cardiovascular and non-cardiovascular causes. Among the secondary outcomes were incidences of myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), stent thrombosis, stroke, and major adverse cardiovascular events (MACEs). In terms of the primary outcomes, the combined analysis revealed a marginally lower risk of all-cause mortality (relative risk, RR (95% CI) = 0.92 (0.85, 1.00), p = 0.05, I2 = 0%) with the use of PF-DES versus PC-DES. Nonetheless, there was no significant difference in cardiovascular mortality (RR (95% CI) = 0.97 (0.87, 1.08)) or non-cardiovascular mortality (RR (95% CI) = 0.87 (0.69, 1.10), p = 0.25, I2 = 9%) between the groups. Furthermore, univariate meta-regression revealed that male gender and prior myocardial infarction were independently associated with an increased risk of all-cause mortality and cardiovascular disease. According to the current meta-analysis, no statistically significant differences existed in PF-DES and PC-DES outcomes. More extensive research is needed to investigate these findings further and establish their validity.

Fluoroquinolone-Induced Sweet Syndrome: A Case Report.

Sweet syndrome (SS) is a rare non-vasculitic neutrophilic dermatosis. Fever, the abrupt emergence of tender erythematous plaques and nodules, with an occasional presentation of vesicles and pustules along with dense neutrophilic infiltrates on skin biopsy are the hallmarks of the illness. Tender plaques or nodules develop along with other systemic manifestations suddenly in affected people which is considered to occur due to immune-mediated hypersensitivity. We report a case of Sweet syndrome in Pakistan presenting in a 55-year-old female. It is worth reporting due to the rarity of such cases in this region. The patient was diagnosed after profound investigations and was treated with corticosteroid therapy.

Treatment with Testosterone Therapy in Type 2 Diabetic Hypogonadal Adult Males: A Systematic Review and Meta-Analysis.

Testosterone replacement therapy (TRT) has been used to treat hypogonadal males with type 2 diabetes mellitus (T2DM) for a long time, despite variable results. This meta-analysis examines TRT's role in hypogonadal males with T2DM. The databases PubMed, Embase, and Google Scholar were searched for relevant RCTs and observational studies. Estimated pooled mean differences (MDs) and relative risks with 95% confidence intervals were used to measure the effects of TRT (CIs). When compared to the placebo, TRT improves glycemic management by significantly reducing glycated hemoglobin (HBA1c) levels (WMD = -0.29 [-0.57, -0.02] p = 0.04; I2 = 89.8%). Additionally, it reduces the homeostatic model assessment levels of insulin resistance (WMD = -1.47 [-3.14, 0.19]; p = 0.08; I2 = 56.3%), fasting glucose (WMD = -0.30 [-0.75, 0.15]; p = 0.19; I2 = 84.4%), and fasting insulin (WMD = -2.95 [-8.64, 2.74]; however, these results are non-significant. On the other hand, HBA1c levels are significantly reduced with TRT; in addition, total testosterone levels significantly increase with testosterone replacement therapy (WMD = 4.51 [2.40, 6.61] p = 0.0001; I2 = 96.3%). Based on our results, we hypothesize that TRT can improve glycemic control and hormone levels, as well as lower total cholesterol, triglyceride, and LDL cholesterol levels while raising HDL cholesterol in hypogonadal type 2 diabetes patients. To this end, we recommend TRT for these patients in addition to standard diabetes care.

Risk of Stroke With Mitral Stenosis: The Underlying Mechanism, Treatment, and Prevention.

Mitral stenosis (MS), a valvular heart disease, is defined by the narrowing of the mitral valve orifice. The common risk factors for stroke include mitral annular calcification (MAC), diabetes mellitus (DM), male gender, hypertension (HTN), hyperlipidemia, and obesity. Endothelial damage, hypercoagulability, and blood stasis in the left atrium promote the development of the thrombus. Among all the risk factors described, MAC is the independent predictor of stroke. The complicated mechanisms responsible for thromboembolism, predisposing factors for thromboembolism, the risk of cerebrovascular accident (CVA) in MS patients, advanced standardized assessment models for identifying those at risk for stroke, and the possible advantages and disadvantages of available therapies have all been discussed in this review article. We have also discussed newer oral anticoagulants (NOACs) like dabigatran, edoxaban, apixaban, and rivaroxaban. Non-pharmacological therapies are also highlighted such as left atrial appendage ligation and occlusion devices. We also conducted a thorough review of the literature on the efficacy and safety of various NOACs in reducing the risk of stroke.

Cirrhosis and Coagulopathy: Mechanisms of Hemostasis Changes in Liver Failure and Their Management.

Cirrhosis is an end-stage liver disease that can cause changes in any component of the hemostatic system. The net effects of the complicated hemostatic changes have long been unknown due to concurrent changes in pro-and antihemostatic drivers. Coagulation disorders are caused by various factors, including decreased clotting and inhibitor factor synthesis, reduced clearance of activated factors, quantitative and qualitative platelet defects, hyperfibrinolysis, and increased intravascular coagulation. This review discusses the pathogenesis of coagulopathy and multiple studies related to its clinical presentations. This article also highlights an additional problem in the diagnostic and therapeutic approach to this group of patients: the fact that traditional coagulation tests and transfusional strategies may not be reliable for assessing and managing bleeding or thrombotic risks. Hence, multiple management options have been assessed for bleeding and thrombosis in liver disease.

Ulcerative Colitis-Induced Colorectal Carcinoma: A Deleterious Concatenation.

Inflammatory bowel disease (IBD) is a chronic inflammatory gastrointestinal ailment that encompasses Crohn's disease (CD) and ulcerative colitis (UC). UC is an idiopathic, chronic inflammatory condition of the colonic mucosa that begins in the rectum and progresses proximally in a continuous way over a portion of the entire colon. Chronic inflammation is linked to cancer, and IBD-related chronic colonic inflammation raises the risk of colorectal cancer. Chronic inflammation has been linked to cancer, and chronic colonic inflammation caused by IBD increases the risk of colorectal cancer (CRC). When CRC arises in people with IBD, unlike sporadic CRC, the lesions are difficult to identify due to mucosal alterations produced by inflammation. The total prevalence of IBD-associated CRC is increasing due to the rapidly increasing frequency of IBD. Screening and surveillance colonoscopy in IBD patients is considered to allow for the early diagnosis of dysplasia and cancer, improving the prognosis of IBD-related CRC by giving patients proactive therapy. This article has reviewed literature pertaining to the mechanisms related to CRC development in UC and its clinical and therapeutic implications.