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.

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.

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.

The Impact of the COVID-19 Pandemic on Myopia Progression in Children: A Systematic Review.

Myopia is the most common refractive error among children. The coronavirus disease 2019 (COVID-19) pandemic has affected children's health in many ways. Policy changes due to the COVID-19 pandemic, such as home quarantine and online schooling, have been proposed as causes for the increased risk of myopia progression. During strict home quarantine, children spend less time outdoors and more time using electronic devices which are important risk factors associated with myopia. Our systematic review aims to assess the relationship between myopia progression and these risk factors in children. We did the literature search from PubMed, Google Scholar, and ScienceDirect. A total of 10 research papers were selected for final review using the Preferred Reporting Item for Systematic Review and Meta-Analyses (PRISMA) guidelines. The research articles used had a quality of more than 70%. The quality of these articles was determined using the Joanna Briggs Institute (JBI) tool. Our review included eight cross-sectional and two cohort studies. Most of these studies used questionnaires to assess the risk factors of myopia. Standardized ocular examinations were done in most studies to measure visual acuity, spherical equivalent, and axial lengths. Our study found that the progression of myopia was affected by the reduced time spent outdoors and increased screen time during the pandemic. We also found that children's increased use of electronic devices, such as mobile phones and tablets, has significantly affected myopia progression during the pandemic.

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.

A Systematic Review on Whether an Association Exists Between Adolescent Obesity and Idiopathic Intracranial Hypertension.

Pseudotumor cerebri syndrome (PTCS)/idiopathic intracranial hypertension (IIH) is a clinical presentation appertaining to signs/symptoms of raised intracranial pressure, like headache and papilledema. It is an uncommon but clinically significant cause of morbidity such as permanent vision loss. It is crucial to understand if idiopathic intracranial hypertension (IIH) is on the rise in adolescents, it is probably due to the rising prevalence of obesity worldwide. Our study aimed to find an association between obesity and IIH in adolescents. We utilized Preferred Reporting Items for Systematic Review and Meta-Analysis 2020 (PRISMA) guidelines to run this systematic review. Many publications related to the topic in the discussion were scrutinized through a comprehensive database search. We filtered them down to a final count of 10 articles after utilizing our inclusion/exclusion criteria and assessing the quality of work. In these final papers, we identified several possibilities to explain the link between obesity and IIH in adolescents. Overweight and obese adolescents were found to have a significantly increased risk of IIH development, with a more severe clinical picture seen in morbidly obese female patients.

Utility of N-terminal (NT)-Brain Natriuretic Peptide (proBNP) in the Diagnosis and Prognosis of Pregnancy Associated Cardiovascular Conditions: A Systematic Review.

Cardiovascular disease includes many diseases such as heart failure, cardiomyopathy, valvular disease, pericardial disease, peripheral vascular disease, rheumatic heart disease, and vascular disease to name a few. Cardiovascular disease in pregnancy is on the rise especially with women being pregnant at an older age. Brain natriuretic peptide (BNP) could be a factor in determining the severity. BNP is elevated in heart failure. This study will attempt to determine the relationship between BNP and pregnancy outcomes in women with heart failure. A keyword combination search was performed using varying databases. Inclusion and exclusion criteria were implemented and relevant articles were obtained to formulate ideas to support the topic. BNP, the amino acid peptide, is secreted by both atrial and ventricular monocytes. BNP and N-terminal (NT)-pro hormone BNP (NT-proBNP) are elevated in heart failure and seen in pregnant women alike. Within six to 12 weeks it returns to normal levels. Normal levels were shown to have good pregnancy outcomes in that the baby is healthy with normal birth weight and the mother is free of cardiovascular complications, whereas at elevated levels the pregnancy outcome was not favorable. NT-proBNP, when elevated in the pregnant patient, is a predictor of poor pregnancy outcomes, especially in patients with precursors. Testing for this peptide in pregnant women during the early stages of pregnancy could help determine the best course of action for a better outcome.

Reduced left ventricular dimension and function following early life stress: A thrifty phenotype hypothesis engendering risk for mood and anxiety disorders.

BACKGROUND: Early life stress (ELS) in macaques in the form of insecure maternal attachment putatively induces epigenetic adaptations resulting in a "thrifty phenotype" throughout the life cycle. For instance, ELS induces persistent increases in insulin resistance, hippocampal and corpus callosum atrophy and reduced "behavioral plasticity", which, taken together, engenders an increased risk for mood and anxiety disorders in humans but also a putative sparing of calories. Herein, we test the hypothesis whether a thrifty phenotype induced by ELS is peripherally evident as hypotrophy of cardiac structure and function, raising the possibility that certain mood disorders may represent maladaptive physiological and central thrift adaptations. METHODS: 14 adult bonnet macaques (6 males) exposed to the maternal variable foraging demand (VFD) model of ELS were compared to 20 non-VFD adult subjects (6 males). Left ventricle end-diastolic dimension (LVEDD), Left ventricle end-systolic dimension (LVESD) and stroke volume (SV) were calculated using echocardiography. Blood pressure and heart rate were measured only in females. Previously obtained neurobehavioral correlates available only in males were analyzed in the context of cardiac parameters. RESULTS: Reduced LVESD (p < 0.05) was observed when controlled for age, sex, body weight and crown-rump length whereas ejection fraction (EF) (p = 0.037) was greater in VFD-reared versus non-VFD subjects. Pulse pressure was lower in VFD versus non-VFD females (p < 0.05). Male timidity in response to a human intruder was associated with reduced LVEDD (p < 0.05). CONCLUSIONS: ELS is associated with both structural and functional reductions of left ventricular measures, potentially implying a body-wide thrifty phenotype. Parallel "thrift" adaptations may occur in key brain areas following ELS and may play an unexplored role in mood and anxiety disorder susceptibility.

Treating comorbid anxiety and depression: Psychosocial and pharmacological approaches.

Comorbid anxiety with depression predicts poor outcomes with a higher percentage of treatment resistance than either disorder occurring alone. Overlap of anxiety and depression complicates diagnosis and renders treatment challenging. A vital step in treatment of such comorbidity is careful and comprehensive diagnostic assessment. We attempt to explain various psychosocial and pharmacological approaches for treatment of comorbid anxiety and depression. For the psychosocial component, we focus only on generalized anxiety disorder based on the following theoretical models: (1) "the avoidance model"; (2) "the intolerance of uncertainty model"; (3) "the meta-cognitive model"; (4) "the emotion dysregulation model"; and (5) "the acceptance based model". For depression, the following theoretical models are explicated: (1) "the cognitive model"; (2) "the behavioral activation model"; and (3) "the interpersonal model". Integration of these approaches is suggested. The treatment of comorbid anxiety and depression necessitates specific psychopharmacological adjustments as compared to treating either condition alone. Serotonin reuptake inhibitors are considered first-line treatment in uncomplicated depression comorbid with a spectrum of anxiety disorders. Short-acting benzodiazepines (BZDs) are an important "bridging strategy" to address an acute anxiety component. In patients with comorbid substance abuse, avoidance of BZDs is recommended and we advise using an atypical antipsychotic in lieu of BZDs. For mixed anxiety and depression comorbid with bipolar disorder, we recommend augmentation of an antidepressant with either lamotrigine or an atypical agent. Combination and augmentation therapies in the treatment of comorbid conditions vis-à-vis monotherapy may be necessary for positive outcomes. Combination therapy with tricyclic antidepressants, gabapentin and selective serotonin/norepinephrine reuptake inhibitors (e.g., duloxetine) are specifically useful for comorbid chronic pain syndromes. Aripiprazole, quetiapine, risperidone and other novel atypical agents may be effective as augmentations. For treatment-resistant patients, we recommend a "stacking approach" not dissimilar from treatment of hypertension In conclusion, we delineate a comprehensive approach comprising integration of various psychosocial approaches and incremental pharmacological interventions entailing bridging strategies, augmentation therapies and ultimately stacking approaches towards effectively treating comorbid anxiety and depression.

Elevated cerebrospinal fluid 5-hydroxyindoleacetic acid in macaques following early life stress and inverse association with hippocampal volume: preliminary implications for serotonin-related function in mood and anxiety disorders.

BACKGROUND: Early life stress (ELS) is cited as a risk for mood and anxiety disorders, potentially through altered serotonin neurotransmission. We examined the effects of ELS, utilizing the variable foraging demand (VFD) macaque model, on adolescent monoamine metabolites. We sought to replicate an increase in cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) observed in two previous VFD cohorts. We hypothesized that elevated cisternal 5-HIAA was associated with reduced neurotrophic effects, conceivably due to excessive negative feedback at somatodendritic 5-HT1A autoreceptors. A putatively decreased serotonin neurotransmission would be reflected by reductions in hippocampal volume and white matter (WM) fractional anisotropy (FA). METHODS: When infants were 2-6 months of age, bonnet macaque mothers were exposed to VFD. We employed cisternal CSF taps to measure monoamine metabolites in VFD (N = 22) and non-VFD (N = 14) offspring (mean age = 2.61 years). Metabolites were correlated with hippocampal volume obtained by MRI and WM FA by diffusion tensor imaging in young adulthood in 17 males [10 VFD (mean age = 4.57 years)]. RESULTS: VFD subjects exhibited increased CSF 5-HIAA compared to non-VFD controls. An inverse correlation between right hippocampal volume and 5-HIAA was noted in VFD- but not controls. CSF HVA and MHPG correlated inversely with hippocampal volume only in VFD. CSF 5-HIAA correlated inversely with FA of the WM tracts of the anterior limb of the internal capsule (ALIC) only in VFD. CONCLUSIONS: Elevated cisternal 5-HIAA in VFD may reflect increased dorsal raphe serotonin, potentially inducing excessive autoreceptor activation, inducing a putative serotonin deficit in terminal fields. Resultant reductions in neurotrophic activity are reflected by smaller right hippocampal volume. Convergent evidence of reduced neurotrophic activity in association with high CSF 5-HIAA in VFD was reflected by reduced FA of the ALIC.