Tachy-brady syndrome: Electrophysiology and evolving principles of management.

Sudden alterations in the heart rate may be associated with diverse symptoms. Sinus node dysfunction (SND), also known as sick sinus syndrome, is a sinoatrial (SA) node disorder. SND is primarily caused by the dysfunction of the pacemaker, as well as impaired impulse transmission resulting in a multitude of abnormalities in the heart rhythms, such as bradycardia-tachycardia, atrial bradyarrhythmias, and atrial tachyarrhythmias. The transition from bradycardia to tachycardia is generally referred to as "tachy-brady syndrome" (TBS). Although TBS is etiologically variable, the manifestations remain consistent throughout. Abnormal heart rhythms have the propensity to limit tissue perfusion resulting in palpitations, fatigue, lightheadedness, presyncope, and syncope. In this review, we examine the physiology of tachy-brady syndrome, the practical approach to its diagnosis and management, and the role of adenosine in treating SND.

Precision Medicine and Cardiac Channelopathies: Human iPSCs Take the Lead.

Sudden cardiac death (SCD) is one of the leading causes of death worldwide, usually involving young people. SCD remains a critical public health problem accounting for 185,000-450,000 deaths annually, representing around 7%-18% of all deaths globally. As per evidence, ∼2%-54% of sudden unexpected deaths in people under the age of 35 years fail to show evidence of structural cardiac abnormalities at autopsy, making ion channelopathies the probable causes in such cases. The most generally recognized cardiac ion channelopathies with genetic testing are long QT syndrome (LQTS), Brugada syndrome (BrS), short QT syndrome (SQTS), and catecholaminergic polymorphic ventricular tachycardia (CPVT). The substantial progress in understanding the genetics of ion channelopathies in the last 2 decades has obliged the early diagnosis and prevention of SCD to a certain extent. In this review, we analyze the critical challenges and recent advancements in the identification, risk stratification, and clinical management of potentially fatal cardiac ion channel disorders. We also emphasize the application of precision medicine (PM) and artificial intelligence (AI) for comprehending the underlying genetic mechanisms, especially the role of human induced pluripotent stem cell (iPSC) based platforms to unravel the primary refractory clinical problems associated with channelopathies.

Colonic diverticular bleeding: An update on pathogenesis and management.

Colonic diverticular bleeding is the most common cause of lower gastrointestinal (GI) bleeding, which can be life-threatening and frequently recurrent. In recent years, the prevalence of diverticulosis has increased in developed countries, with a documented incidence of 50% in patients older than 60 years. Based on the evidence, the use of anticoagulants and/or antiplatelets in the elderly population has resulted in an increased incidence of acute diverticular bleeding. According to the literature, about 50% of patients with diverticular bleeding require a blood transfusion, and 18% - 53% need emergency surgery. Although endoscopic identification of the culprit diverticula and appropriate intervention is a challenge, the newer treatment modality, over-the-scope clip method (OTSC) has been demonstrated to be an effective endoscopic hemostatic method in severe diverticular bleeding, especially in cases of rebleeding after first-line conventional endoscopic procedures. In this review, we summarize the pathophysiology of colonic diverticulosis and diverticular bleeding, recent evidence in its management, and existing theories on various preventive strategies to control diverticular bleeding. We also discuss the efficacy and treatment outcome of the OTSC technique in controlling diverticular bleeding.

Hypertrophic Cardiomyopathy: Current Treatment and Future Options.

Hypertrophic cardiomyopathy (HCM) is a disease involving the cardiac sarcomere. It is associated with various disease-causing gene mutations and phenotypic expressions, managed with different therapies with variable prognoses. The heterogeneity of the disease is evident in the fact that it burdens patients of all ages. HCM is the most prevalent cause of sudden death in athletes. However, several technological advancements and therapeutic options have reduced mortality in patients with HCM to 0.5% per year. In addition, rapid advances in our knowledge of the molecular defects accountable for HCM have strengthened our awareness of the disorder and recommended new approaches to the assessment of prognosis. Despite all these evolutions, a small subgroup of patients with HCM will experience sudden cardiac death, and risk stratification remains a critical challenge. This review provides a practical guide to the updated recommendations for patients with HCM, including clinical updates for diagnosis, family screening, clinical imaging, risk stratification, and management.

A Systematic Review of the Risk of Non-alcoholic Fatty Liver Disease in Women With Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a complex hormonal disorder associated with complications throughout various body organs. Previous studies have shown evidence of liver disease in some women with PCOS. In this study, we attempted to explore the risk of non-alcoholic fatty liver disease (NAFLD) in PCOS women and the specific factors involved in its development. We searched PubMed, PubMed Central, Medline, and ScienceDirect for articles related to the topic, screened those articles according to our inclusion/exclusion criteria, and conducted a thorough quality check using various quality appraisal tools to select articles relevant to our research. The process was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) Checklist 2020. We selected 11 high-quality observational studies for our review. Studies from various countries were included, and all studies demonstrated an increased prevalence of NAFLD in PCOS patients compared to healthy controls. Although insulin resistance, obesity, and increased androgens contribute to the increase in the risk of NAFLD in these patients, hyperandrogenism was the most influential risk factor in four of these studies. Two studies explored the degree of NAFLD in these patients using transient elastography (TE). They concluded that PCOS was significantly associated with hepatic steatosis (HS) rather than hepatic fibrosis in most patients. PCOS patients have an increased risk of developing NAFLD, particularly HS, and hyperandrogenism seems to be the main determinant. Therefore, effort should be put into screening and monitoring these patients to manage the disease. TE may be a useful method for monitoring the natural history of NAFLD in these patients, which requires further exploration.

Role of Vitamin D Deficiency in Increased Susceptibility to Respiratory Infections Among Children: A Systematic Review.

Vitamin D has several roles in the immune system besides its effects on bone metabolism. Acute respiratory infections are common infections in children. Severe lower respiratory tract infections (LRTIs) even cause death in children, especially in those less than five years of age. Our study aims to examine whether children with vitamin D deficiency are susceptible to respiratory infections and to study the association between vitamin D deficiency and the severity of respiratory infections. We comprehensively searched research articles in PubMed, ScienceDirect, and Cochrane library databases. The main keywords were vitamin D deficiency, respiratory infections, and children. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines to conduct this systematic review. The initial search showed 16,120 papers. A meticulous screening of research articles using the eligibility criteria and quality appraisal tools was done. Finally, 10 research articles qualified for this systematic review, including eight case-control studies, one randomized controlled trial (RCT), and one cohort study. Seven of 10 research studies reviewed found that children with low vitamin D levels are susceptible to respiratory infections. Five studies discussed the severity of respiratory infections and low vitamin D levels. This systematic review concluded that children with low vitamin D levels are prone to developing respiratory infections. But we could not find a conclusive association between the severity of respiratory infections and low vitamin D levels.

Association Between Helicobacter pylori Infection and the Risk of Pancreatic Cancer: A Systematic Review Based on Observational Studies.

Helicobacter pylori (H. pylori) bacterial infection has long been scrutinized as one of the potential risk factors for the development of pancreatic cancer with quite inconsistent and unequivocal data. Little is known about the risk factors involved with this malignancy. In this systematic review, we aimed to examine the relationship between H. pylori infection and pancreatic cancer based on the evidence from the existing observational studies across the world. We searched major electronic databases such as PubMed, MEDLINE, Science Direct, and Cochrane Library. After a careful and thorough screening process, we selected 15 observation studies for this systematic review. Six of 15 studies found a significant association between H. pylori infection and pancreatic cancer. Additionally, four of these studies found a significant relationship between the cytotoxin-associated gene A strain of H. pylori and pancreatic cancer. Based on the evidence from the selected studies, a weak association was observed between H. pylori infection and cancer of the pancreas, especially in European and Asian populations compared to the North American population. The cross-sectional evidence from the case-control studies only suggests the existence of an association but does not provide substantial evidence of the causative relationship. Further large-scale, prospective cohort studies are warranted in the future to understand this contradictory relationship better.

Exploring the Efficacy of Alirocumab and Evolocumab in Reducing Low-Density Lipoprotein (LDL) Cholesterol Levels in Patients With Familial Hypercholesterolemia: A Systematic Review.

Patients with familial hypercholesterolemia (FH) have an increased risk of having abnormally high low-density lipoprotein cholesterol (LDL-C) levels. One of the main groups of drugs used for FH is statins. However, even with statins, most patients with FH do not achieve their pre-defined therapeutic LDL-C goals. Therefore, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) serve to decrease LDL-C levels in that population. A total of 838 articles were found after searching the databases of PubMed, MEDLINE, and Cochrane Library. After including only full-text peer-reviewed articles published in the last 10 years, 67 articles remained. Thirteen articles were put through the Cochrane bias assessment tool to screen for bias. After a strict quality assessment based on the criteria, eight articles were extracted and included in this systematic review. The data extraction from these studies showed that alirocumab and evolocumab were efficacious in decreasing LDL-C levels and achieving the pre-defined LDL-C goals. Many parameters influenced the strength of the LDL-C reduction: sample size of the population, genetic structure of the patients affected by FH, length of the trial, or baseline lipid-lowering therapy used. Therefore, one must consider several other factors while evaluating the percent reduction of PCSK9i. This review is limited because it did not comment on these drugs' cardiovascular outcomes or mortality benefits. In addition, some of the articles used in this systematic review have small sample sizes and short trial times, limiting the long-term evaluation of these drugs.

Efficacy of Dengue Vaccines in the Prevention of Severe Dengue in Children: A Systematic Review.

Dengue is a vector-borne disease caused by the dengue virus (DENV) and is a major health concern worldwide, particularly in regions of endemic disease. Dengue usually presents as a self-limited febrile illness. In some cases, more severe forms with hemorrhage and shock can occur, and children are especially prone to develop it. These forms can be lethal without appropriate management, and no antiviral treatment exists today. In the absence of a curative treatment for dengue, its clinical prevention remains essential. One vaccine - the chimeric yellow fever-dengue-tetravalent dengue vaccine (CYD-TDV) - has been approved for use in some populations, and several others are currently in development, including Takeda's tetravalent dengue vaccine candidate (TAK-003). This study is a systematic review of the current literature realized to evaluate the efficacy of the dengue vaccines in preventing severe dengue in children. This review focuses on the vaccines CYD-TDV and TAK-003. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, PubMed Central (PMC), Medical Literature Analysis and Retrieval System Online (MEDLINE), Cochrane Library, and Google Scholar were the databases used to find the relevant data. The articles were selected using specific inclusion and exclusion criteria, and quality appraisal was realized with standardized quality assessment tools. Overall, our study shows that the dengue vaccines CYD-TDV and TAK-003 confer protection against severe dengue in children. Some distinctions exist depending on the vaccine type, the age, and the dengue serostatus of patients. While demonstrating encouraging results, this review also emphasizes the need for more in-depth studies about the safety and efficacy of dengue vaccines.

Postural Orthostatic Tachycardia Syndrome (POTS): An Update for Clinical Practice.

Postural Orthostatic Tachycardia Syndrome (POTS) is a variant of autonomic cardiovascular disorder characterized by an excessive increase in heart rate upon standing associated with light-headedness, headaches, chest pain, shortness of breath, and brain fog. The etiology of POTS is largely unknown and often debilitating. The 3 major hypotheses about the pathophysiology of POTS are autoimmunity, abnormally increased sympathetic activity, and sympathetic denervation leading to central hypovolemia and reflex tachycardia. Given its heterogeneous nature, it is crucial to understand each component of POTS with more emphasis on incorporating a multidisciplinary approach to control the symptoms. Future works should focus on better understanding the POTS pathophysiology and designing randomized controlled trials for implementing effective therapy. In this review, we outline the extent of the problem, studies and resources needed to address the issue, and the diagnostic and therapeutic updates on POTS.