Correlation of Leptin in Patients With Type 2 Diabetes Mellitus.

The exponential increase in diabetes mellitus (DM) poses serious public health concerns. In this review, we focus on the role of leptin in type 2 DM. The peripheral actions of leptin consist of upregulating proinflammatory cytokines which play an important role in the pathogenesis of type 2 DM and insulin resistance. Moreover, leptin is known to inhibit insulin secretion and plays a significant role in insulin resistance in obesity and type 2 DM. A literature search was conducted on Medline, Cochrane, Embase, and Google Scholar for relevant articles published until December 2023. The following search strings and Medical Subject Headings (MeSH terms) were used: "Diabetes Mellitus," "Leptin," "NPY," and "Biomarker." This article aims to discuss the physiology of leptin in type 2 DM, its glucoregulatory actions, its relationship with appetite, the impact that various lifestyle modifications can have on leptin levels, and, finally, explore leptin as a potential target for various treatment strategies.

Role of gene therapy in sickle cell disease.

BACKGROUND: Gene therapy is an emerging treatment for sickle cell disease that works by replacing a defective gene with a healthy gene, allowing the body to produce normal red blood cells. This form of treatment has shown promising results in clinical trials, and is a promising alternative to traditional treatments. Gene therapy involves introducing a healthy gene into the body to replace a defective gene. The new gene can be delivered using a viral vector, which is a modified virus that carries the gene. The vector, carrying the healthy gene, is injected into the bloodstream. The healthy gene then enters the patient's cells and begins to produce normal hemoglobin, the protein in red blood cells that carries oxygen throughout the body. METHODOLOGY: We conducted an all-language literature search on Medline, Cochrane, Embase, and Google Scholar until December 2022. The following search strings and Medical Subject Heading (MeSH) terms were used: "Sickle Cell," "Gene Therapy" and "Stem Cell Transplantation". We explored the literature on Sickle Cell Disease for its epidemiology, etiopathogenesis, the role of various treatment modalities and the risk-benefit ratio of gene therapy over conventional stem cell transplant. RESULTS: Gene therapy can reduce or eliminate painful episodes, prevent organ damage, and raise the quality of life for those living with the disease. Additionally, gene therapy may reduce the need for blood transfusions and other traditional treatments. Gene therapy has the potential to improve the lives of those living with sickle cell disease, as well as reduce the burden of the disease on society.

Enteric Fever: Diagnostic Challenges and the Importance of Early Intervention.

Enteric fever is a systemic infection caused by highly virulent Salmonella enterica serovars: Typhi and Paratyphi. Diagnosis of enteric fever is challenging due to a wide variety of clinical features which overlap with other febrile illnesses. The current diagnostic methods are limited because of the suboptimal sensitivity of conventional tests like blood culture in detecting organisms and the invasive nature of bone marrow culture. It emphasizes the need to develop improved and more reliable diagnostic modalities. The rising rates of multidrug-resistant Salmonella strains call for an accurate understanding of the current management of the disease. Proper public health measures and large-scale immunization programs will help reduce the burden of the disease. A comprehensive surveillance system can help detect the chronic carrier state and is crucial in understanding antibiotic susceptibility patterns. We conducted an all-language literature search on Medline, Cochrane, Embase, and Google Scholar till May 2022. The following search words and medical subject headings (MeSH) were used: "enteric fever," "Salmonella Typhi," "multidrug-resistant Salmonella," chronic carrier state," "Salmonella detection, "and "typhoid vaccine." We reviewed the literature on clinical features, pathophysiology, new diagnostic tests, and interventions to prevent the disease. This article explores enteric fever and its various clinical features and addresses the emerging threat of multidrug resistance. It focuses on novel methods for diagnosis and prevention strategies, including vaccines and the use of surveillance systems employed across different parts of the world.

Sudden Infant Death Syndrome: Risk Factors and Newer Risk Reduction Strategies.

Sudden infant death syndrome (SIDS) continues to be one of the top causes of infant death in the U.S. Despite significant public health initiatives focused on high-risk populations to enhance sleep environments and techniques. The SIDS rate has remained stable in recent years. Risk factors and newer risk reduction strategies for SIDS are the focus of this review article. We conducted a comprehensive literature search on Medline, Cochrane, Embase, and Google Scholar until July 2022. The following search strings and Medical Subject Heading (MeSH) terms were used: "SIDS," "Sudden Infant Death" and "SUID". We explored the literature on SIDS for its epidemiology, pathophysiology, the role of various etiologies and their influence, associated complications leading to SIDS, and preventive and treatment modalities. Despite a more than 50% drop-in rates since the start of the "Back to Sleep" campaign in 1994, sudden infant death syndrome (SIDS) continues to be the top cause of post-neonatal mortality in the United States, despite continued educational initiatives that support safe sleep and other risk reduction strategies. The new American Academy of Pediatrics guidelines for lowering the risk of SIDS include a lot of emphasis on sleeping habits, bedding, and environment but also include elements that are frequently ignored (i.e., prenatal care, smoking, alcohol and drug use, and childhood vaccinations). This study highlights these less-frequently discussed aspects and identifies treatments that have produced beneficial behavioral shifts that benefit newborns as well as their mothers' health and wellbeing.

Imatinib-Induced Pleuro-Pericardial Effusion and Atrial Fibrillation: An Unusual Side Effect Following the Treatment of a Rare Gastrointestinal Tumor.

Gastrointestinal stromal tumors (GISTs) are one of the most prevalent non-epithelial tumors of the GI mesenchyme. While stromal tumors account for less than 1% of all malignancies, a knowledge of their etiology and signaling pathways can aid in identifying new molecular targets for the potential development of therapeutics. One of the drugs that have shown remarkable action against GIST is imatinib, a tyrosine kinase inhibitor (TKI). We present a case of a female patient with a long-term history of heart failure (HF) with preserved ejection fraction (EF) and minimal pericardial effusion who had recently started imatinib therapy and was hospitalized after new-onset atrial fibrillation (AF) and the development of significantly increased pericardial and pleural effusion. She had been diagnosed with GIST a year ago and started on imatinib. She presented to the ER with complaints of left-sided chest pain. ECG revealed a new AF. The patient was started on rate control and anticoagulation. After a few days, she returned to the ER with complaints of shortness of breath (SOB). The patient was found to have pericardial and pleural effusions on imaging. Fluids from both effusions were aspirated and sent to pathology to rule out malignancy. The patient developed recurrent bilateral pleural effusions after discharge, which were later drained on subsequent hospitalization. Although imatinib is generally well tolerated, it does cause both AF and pleural/pericardial effusions in rare cases. In such cases, it is essential to perform a thorough workup to rule out other possibilities such as metastasis, malignancy, or infection.

Sudden cardiac death in childhood hypertrophic cardiomyopathy.

The most prevalent cause of mortality in children with hypertrophic cardiomyopathy (HCM) is sudden cardiac death (SCD), which happens more frequently than in adult patients. Risk stratification tactics have generally been drawn from adult practice, however emerging data has revealed significant disparities between children and adult cohorts, implying the need for pediatric-specific risk stratification methodologies. We conducted an all-language literature search on Medline, Cochrane, Embase, and Google Scholar until October 2021. The following search strings and Medical Subject Heading (MeSH) terms were used: "HCM," "SCD," "Sudden Cardiac Death," and "Childhood Onset HCM." We explored the literature on the risk of SCD in HCM for its epidemiology, pathophysiology, the role of various genes and their influence, associated complications leading to SCD and preventive and treatment modalities. Childhood-onset HCM is linked to significant life-long morbidity and mortality, including a higher SCD rate in children than in adults. The present focus is on symptom relief and avoiding illness-related consequences, but the prospect of future disease-modifying medicines offers an intriguing opportunity to alter disease expression and outcomes in these young individuals. Current preventive recommendations promote implantable cardioverter defibrillator placement based on cumulative risk factor thresholds, although they have been demonstrated to have weak discriminating capacity. This article addresses questions and discusses the etiology, risk factors, and method to risk stratification for SCD in children with HCM.

Myocarditis in patients on long-term antipsychotics -mechanism, management and recent updates.

Objective: Clozapine is the first atypical antipsychotic drug and was frequently cited as the most effective antipsychotic for treatment-resistant schizophrenia, but it is associated with a concert of significant cardiotoxic side effects. Clozapine-induced Myocarditis (CIM) is diagnosed based on the combination of clinical symptoms, laboratory investigations, radiological findings, and sometimes biopsy. The literature on CIM management and clinical consensus on the best course of action is mixed. Methodology: An all-language literature search on Medline, Cochrane, Embase, and Google Scholar until April 2022. The following search strings and Medical Subject Heading (MeSH) terms were used: "CIM," "clozapine," "cardiotoxicity," and "myocarditis." We explored the literature on CIM for its pathophysiology, diagnosis, monitoring, and management. Results: The clinical features of CIM may be highly variable, ranging from asymptomatic disease to fulminant heart failure, and cessation of medication was the mainstay treatment of CIM, followed by supportive therapy. Other antipsychotics have also been linked with cardiotoxic side effects. Conclusion: Despite being the most effective antipsychotic, clozapine is associated with a cardiotoxic side effect. Current literature suggests that these antipsychotic-related cardiotoxic events impact the treatment selection for schizophrenia and other psychotic disorders, and they must be kept in mind while designing new treatment protocols in the future.

Pulmonary Hypertension in Scleroderma- Evaluation and Management.

Pulmonary Arterial Hypertension (PAH) is a clinical syndrome consisting of physiologic/hemodynamic criteria that are a consequence of several etiologies. Systemic Sclerosis (SSc), one of the most common causes of PAH, is an autoimmune disorder of the connective tissue leading to fibrosis that involves the skin, gastrointestinal tract, lungs, heart, kidney etc. SSc has an annual prevalence of one to five cases for every 1000 individuals and nearly 15 percent of all cases develop PAH. At its core, Pulmonary hypertension (PH) in SSc is an obliterative vasculopathy in small to medium-sized pulmonary arterioles. A host of other local and systemic mechanisms operate in concert to gradually alter the hemodynamics resulting in elevated pulmonary vascular resistance and thus right ventricular afterload. A diagnosis of PAH in SSc is virtually a death sentence, with studies reporting a mortality rate of 50 per cent in the 3 years of diagnosis. Therefore, developing and implementing a robust screening and diagnosis protocol is crucial in the fight against this pervasive disease. This review aims to summarize the current literature of PAH in SSc, with a special focus on the screening and diagnosis protocols, newer treatment options and prognostic indicators for the same.

Idiopathic pulmonary fibrosis: Diagnosis, biomarkers and newer treatment protocols.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung condition marked by lung scarring that progresses over time and with usual interstitial pneumonia histology (UIP). It is linked to a worsening cough, dyspnea, and a worse quality of life. Around 3 million persons worldwide suffer from IPF, and the prevalence rises sharply with advancing age. The detection of the UIP pattern, generally using high-resolution CT; lung biopsy may be necessary in certain individuals; the diagnostic approach also includes the elimination of other interstitial lung illnesses or overlapping problems. The UIP pattern is mostly bilateral, peripheral, and basal, with clusters of subpleural cystic airspaces and reticular alterations linked to traction bronchiectasis. Although there are still many uncertainties about how to define susceptibility, it is believed that the molecular mechanisms causing IPF reflect an abnormal reparative response to repeated alveolar epithelial damage in an aging genetically sensitive individual. With the availability of two pharmacotherapeutic drugs, pirfenidone and nintedanib, that slow physiological advancement and potentially increase progression-free survival, significant progress has been made in our knowledge of the clinical treatment of IPF. The goal of current research is to develop early biomarkers for IPF that may include circulating variables, demographic information, and imaging data.

Current Limitations and Recent Advances in the Management of Asthma.

BACKGROUND: Asthma is a significant worldwide health issue affecting kids and adults. Asthma management is mainly straightforward, but considering the associated co-morbidities, it is essential to diagnose the disease accurately. Steroid resistance and dependence, along with inhaler abuse, are the other challenges in clinical practice. Despite being treated with the recommended guidelines, a good portion of the population has persistent symptoms. Emerging biological treatments can alter the global landscape of managing severe asthma. With these new therapeutic possibilities, phenotype- and endotype-specific therapies can be used to individualize treatment plans. METHODOLOGY: We searched Medline, Embase, Google Scholar, and PubMed until March 2022 for all types of literature. Medical Subject Heading (MeSH) terms such as "asthma," "pathogenesis," "diagnosis and classification," "comorbidities," "treatments," "inhaler abuse & corticosteroid resistance," and "biologics" were used in the searches. To better understand the disease, we analyzed the literature on asthma regarding pathophysiology, diagnostic criteria, endotypic and phenotypic classification, comorbidities, existing treatment guidelines, management challenges, and potential for biologics in uncontrolled cases. RESULTS: After exploring the data, our review article aims to highlight current limitations in the clinical management of asthma and the advances in treating asthma. CONCLUSION: Clinical practice should consider an integrative approach to the care and prevention of asthma. We advocate for a large-scale cohort of observation studies and RCTs that further look into the underlying immunological mechanisms, the function of hereditary and environmental variables, and the novel molecular targets of asthma in light of the rising incidence and prevalence of the disease. Even with rising steroid resistance and dependence, the standard therapy will be the mainstream of asthma management. Biologics have promiscuous results and the potential for changing the treatment of uncontrolled asthma. Optimizing the standard therapy with biologics is needed to decrease asthma-related morbidity.

Deep Brain Stimulation in the Treatment of Parkinson's Disease.

Parkinson's disease (PD) is a common progressive neurodegenerative movement disorder. The cardinal feature of Parkinson's is neuronal degeneration causing a dopamine deficit in the brain which leads to a host of clinical features in the patient. However, consensus over specific clinical criteria for diagnosis remains to be established. Parkinson's does not have a cure yet, but a variety of diagnostic and treatment protocols have been developed over the years with a primary focus on pharmacological therapy. Anti-parkinsonian drugs such as levodopa lose their efficacy over time and are needed in higher doses as the disease inevitably progresses. An alternative to pharmacological therapy is deep brain stimulation (DBS). Deep brain stimulation involves transcranial placement of unilateral or bilateral leads (wires) most commonly in the sub-thalamic nucleus or the globus pallidus interna of the brain by stereotactic surgery. Given the multiple hypotheses explaining the different effects of DBS with sometimes conflicting mechanisms, it is difficult to pinpoint the exact way in which DBS operates. Nevertheless, it has proven to be significantly effective. DBS, although being a cost-effective treatment measure for Parkinson's patients, is not without limitations. A careful selection of patients is required preoperatively that determines the response and tolerance to the therapy in patients. This review aims to summarize the current literature on DBS in Parkinson's with a focus on the hypothesized mechanisms, selection criteria, advantages and its limitations.

Pediatric Autoimmune Neuropsychiatric Disorders Associated With Group A Streptococci: Etiopathology and Diagnostic Challenges.

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) have attracted a lot of interest and discussion since it was originally characterized in 1998. The role of streptococcal infection in children with abrupt-onset obsessive-compulsive disorder (OCD) and new-onset tics, the natural history of this entity, and the role of symptomatic and disease-modifying therapies, such as antibiotics, immunotherapy, and psychoactive drugs, are still unresolved issues. Alternative therapies for acute-onset OCD have been developed based on this postulated pathophysiology, including antibiotics and immunomodulatory therapy. The literature on PANDAS therapy is varied but there is no clinical consensus on the treatment of choice. While there is no convincing evidence for the autoimmune rationale for PANDAS, given the increased attention to this entity and the apparent growth in usage of this diagnostic category, it is critical to address concerns about the condition's diagnosis, treatment, and pathogenesis. We conducted a multi-language literature search on Medline, Cochrane, Embase, and Google Scholar for a period spanning until October 2021. The following search strings and Medical Subject Heading (MeSH) terms were used: "PANDAS," "Group A Streptococcus," "OCD," and "tics." We explored the literature on PANDAS in terms of its epidemiology, pathophysiology, the role of group A streptococcal infection, associated complications, and prophylactic and treatment modalities. We examined current working definitions of PANDAS, analyzed differential diagnoses, and published pieces of evidence for therapies associated with this entity, with a view to proposing a therapeutic strategy for children with acute symptoms that meet PANDAS criteria, in this review article.

Periodic Fever in Children: Etiology and Diagnostic Challenges.

Periodic fever in children is an autoinflammatory illness with an unknown cause. Symptoms include frequent episodes of fever that are followed by an increase in inflammatory markers. A genetic background for periodic fever of unknown origin has been hypothesized, based on its family clustering and parallels to other autoinflammatory illnesses such as familial Mediterranean fever. Genome analysis has been used in studies to look for related gene variations in periodic fever of unknown origin in the pediatric population.  Children with periodic fevers might be a diagnostic challenge. After ruling out the most prevalent causes, a wide variety of other possibilities are investigated. Infectious and noninfectious causes of periodic fever in children are discussed in this article. Inflammasomes (intracellular proteins that activate interleukin (IL)-1b and IL-18) and genetic/hereditary variations are thought to be implicated in the pathogenesis of periodic fever. Evaluation and ruling out possible infective or noninfective causes is vital in the diagnosis of periodic fever in children. Investigations demonstrate that there isn't a single gene linked to it, suggesting that it may have a multifactorial or polygenic origin, with an environmental trigger causing inflammasome activation and fever flares. Treatment is usually symptomatic, with drugs such as colchicine and cimetidine having shown promising results in trials. We explored the literature on periodic fever in children for its epidemiology, pathophysiology, the role of various genes and how they influence the disease and associated complications, and its various treatment modalities.

Nonalcoholic Fatty Liver Disease: An Emerging Modern-Day Risk Factor for Cardiovascular Disease.

Nonalcoholic fatty liver disease (NAFLD), also named metabolic dysfunction-associated fatty liver disease (MAFLD), is a progressive disease spectrum encompassing simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. It is a clinically silent disease leading to multiple extra-hepatic complications/comorbidities. It is an independent risk factor for cardiovascular disease (CVD), increasing susceptibility to hypertension, atherosclerosis, arrhythmia, myocardial dysfunction, cardiac valve deformation, and venous thrombosis through putative mechanisms including systemic inflammation, endothelial dysfunction, oxidative stress, insulin resistance, and altered lipid metabolism. Eventually, it increases the CVD prevalence, incident, and fatality, contributing to a huge health care burden. In fact, CVD is becoming the leading cause of mortality among patients with NAFLD. Other cardiometabolic risk factors coexisting with NAFLD may also accelerate the synergistic development of CVD, which warrants assessment targeting hypertension, diabetes mellitus (DM), obesity, and dyslipidemia to be an integral part of NAFLD care. Monitoring metabolic biomarkers (glucose, glycosylated hemoglobin [HbA1c], insulin, lipids, and lipoproteins), cardiovascular (CV) risk scores (American College of Cardiology/American Heart Association [ACC/AHA] or Framingham), and subclinical atherosclerosis (coronary artery calcification [CAC], carotid intima-media thickness [CIMT], and carotid plaque) are recommended for risk prediction and reduction. There is no universally accepted treatment for NAFLD, and lifestyle changes with weight loss of at least 10% are the mainstay of management. Combination therapy of ezetimibe and statins have a cardioprotective effect and help reduce liver fat. Despite being an emerging risk factor for CVD and its rapidly increasing pattern affecting a quarter of the global population, NAFLD remains overlooked and undetected, unlike the other traditional risk factors. Hence, we conducted a comprehensive narrative review to shed more light on the importance of screening CVD in NAFLD patients. PubMed indexed relevant articles published from 2002 to 2022 (20 years) were searched in April 2022 using medical subject headings (MeSH) as "nonalcoholic fatty liver disease" [Mesh] AND "cardiovascular diseases" [Mesh]. Evidence from 40 observational studies, three clinical trials, one case series, 45 narrative reviews, four systematic reviews and meta-analyses, three systematic reviews, and one meta-analysis were summarized on the epidemiologic data, pathophysiologic mechanisms, clinical features, diagnostic modalities, overlapping management, perceived challenges and health literacy regarding the CVD risk attributed to NAFLD.

The Obesity Paradox in Chronic Heart Disease and Chronic Obstructive Pulmonary Disease.

Obesity in recent years has become an epidemic. A high body mass index (BMI) is one of today's most crucial population health indicators. BMI does not directly quantify body fat but correlates well with easier body fat measurements. Like smoking, obesity impacts multiple organ systems and is a major modifiable risk factor for countless diseases. Despite this, reports have emerged that obesity positively impacts the prognosis of patients with chronic illnesses such as chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD), a phenomenon known as the Obesity Paradox. This article attempts to explain and summarize this phenomenon. As it stands, two theories explain this paradox. The muscle mass hypothesis states that obese patients are better adapted to tide through acute exacerbations due to increased reserve because of greater muscle mass. The other theory focuses on brown adipose tissue and its anti-inflammatory effects on the body. We performed a literature review on research articles published in English from 1983 to the present in the following databases - PubMed, Elsevier, and Google Scholar. The following search strings and Medical Subject Headings (MeSH) terms were used: "Obesity," "Heart Failure," "COPD," and "Cardio-Respiratory Fitness." In this review, we looked at the obesity paradox in Heart Failure and COPD. We summarized the current literature on the Obesity Paradox and reviewed its relationship with Cardio-Respiratory Fitness.

Hypertension and the Role of Dietary Fiber.

Hypertension (HTN) is a leading modifiable risk factor for multiple diseases. It has reached epidemic proportions, affecting nearly a third of the world's population. With such a high prevalence and an exhaustive list of potential complications, antihypertensive therapy has been a subject of focus for the scientific community for a long time. Recently, Dietary fiber is emerging as yet another promising candidate addressing this issue. It is a well-known fact that dietary modification alone can significantly impact a patient's health, with a noticeable effect on BP as well. But simply switching to healthy alternatives is not enough and must happen in tandem with dietary supplementation. The consumption of ultra-processed food has only increased in recent times. Hence, we feel the need to focus on dietary interventions in managing hypertension. This review aims to bring to light the current literature on the pathophysiology, risk factors, and treatment protocols of hypertension, focusing on dietary fibers and their role in hypertension management.

The Risk of Cardiovascular Disease Among Immigrants in Canada.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. The global surge in migration to high-income countries, especially Canada, highlights the importance of studies evaluating the risk factors and the disparities in the rate of incidence of CVD among immigrants. Canada is home to a diverse group of immigrants, each presenting with a risk profile that is unique to their ethnicity and country of birth. A variety of cardiac risk factors, such as dietary habits, physical activity, smoking, cultural traditions as well as preponderance to certain diseases like type II diabetes mellitus, hypertension, and high lipid levels act in concert and impact CVD risk and overall incidence. This narrative review focuses on CVD risks and how it is related to the immigration status among various ethnic groups in Canada.

Diagnostic protocols and newer treatment modalities for cluster headache.

Cluster Headaches are one of the most arguably severe forms of primary headache syndrome that affects humans. Although it is relatively uncommon, it has a significant impact on the quality of life. It is a multifactorial disease that has risk factors ranging from seasonal changes, lifestyle habits to genetics. It occurs in 2 forms- Episodic and Chronic, each having its well-defined Diagnostic Criteria. Moreover, Cluster Headache has an exhaustive list of options for both Preventive and Abortive treatment. This article focuses on Cluster Headache, its pathophysiology, risk factors, differentials, and its diverse treatment modalities. In this study, an all-language literature search was conducted on Medline, Cochrane, Embase, and Google Scholar till October 2021. The following search strings and Medical Subject Headings (MeSH) terms were used: "Cluster Headache," "Triptans," "Neuromodulation," and "Migraine." We explored the literature on Cluster Headache for its epidemiology, pathophysiology, the role of various genes and how they bring about the disease as well as its episodic and chronic variants, and treatment options. Although we have a wide variety of options for Preventive and Abortive therapy, newer more effective pharmacological and non-pharmacological interventions are being developed, and must be integrated into new treatment protocols.

Recent Advances in the Diagnosis and Management of Carcinoid Syndrome.

Carcinoid syndrome, a paraneoplastic condition linked with the release of multiple humoral factors, affects around 30-40% of patients with well-differentiated neuroendocrine tumours. Carcinoid syndrome has a major and unfavourable impact on patients' quality of life; it raises costs when compared to non-functioning neuroendocrine tumours; and it causes patients' lifestyles to alter, such as food, job, physical activity, and social life. Somatostatin analogues have been the first-line therapy for individuals with neuroendocrine tumours and carcinoid disease for decades. While these drugs give considerable relief from carcinoid syndrome symptoms, clinical progression is unavoidable, necessitating further research into newer treatment measures. Carcinoid tumours are sometimes difficult to diagnose because of their vague or nonspecific symptoms. There have been several advancements in all aspects of carcinoid syndrome, as well as novel therapeutics, in the previous few years. New epidemiological studies show that it is becoming more common; increasing insights into the pathogenesis of its various clinical manifestations and its natural history: definition of prognostic factors; new methods to verify its presence; the development of new drugs to treat its various manifestations, both initially and in somatostatin-refractory cases; and an increased understanding of the pathogenesis, natural history, and management of the disease. An all language literature search was conducted on MEDLINE, COCHRANE, EMBASE, and Google Scholar till November 2021. The following search strings and Medical Subject Headings (MeSH) terms were used: "Recent advances", "Carcinoid syndrome", "Neuroendocrine Neoplasms" and "Carcinoid heart disease". We comprehensively reviewed the literature on the pathogenesis, clinical features, and newer treatment modalities for Carcinoid Syndrome. Recent advancements in research and management have resulted from advances in our understanding of the aetiology of carcinoid syndrome. The development of molecular indicators of aggressiveness improved serum tumour markers, and the molecular aetiology of carcinoid heart disease are all possible because of advances in molecular biology. We conducted a comprehensive review to update knowledge regarding the pathophysiology, diagnostic protocols, and current and newer treatments for carcinoid syndrome, which presently requires a multidisciplinary approach, due to the complexity of the illness's aetiology, diagnosis, and therapy.

Management of Steroid-Resistant Nephrotic Syndrome in Children.

Nephrotic syndrome (NS) affects 115-169 children per 100,000, with rates varying by ethnicity and location. Immune dysregulation, systemic circulating substances, or hereditary structural abnormalities of the podocyte are considered to have a role in the etiology of idiopathic NS. Following daily therapy with corticosteroids, more than 85% of children and adolescents (often aged 1 to 12 years) with idiopathic nephrotic syndrome have full proteinuria remission. Patients with steroid-resistant nephrotic syndrome (SRNS) do not demonstrate remission after four weeks of daily prednisolone therapy. The incidence of steroid-resistant nephrotic syndrome in children varies between 35 and 92 percent. A third of SRNS patients have mutations in one of the important podocyte genes. An unidentified circulating factor is most likely to blame for the remaining instances of SRNS. The aim of this article is to explore and review the genetic factors and management of steroid-resistant nephrotic syndrome. An all language literature search was conducted on MEDLINE, COCHRANE, EMBASE, and Google Scholar till September 2021. The following search strings and Medical Subject Headings (MeSH) terms were used: "Steroid resistance", "nephrotic syndrome", "nephrosis" and "hypoalbuminemia". We comprehensively reviewed the literature on the epidemiology, genetics, current treatment protocols, and management of steroid-resistant nephrotic syndrome. We found that for individuals with non-genetic SRNS, calcineurin inhibitors (cyclosporine and tacrolimus) constitute the current mainstay of treatment, with around 70% of patients achieving full or partial remission and an acceptable long-term prognosis. Patients with SRNS who do not react to calcineurin inhibitors or other immunosuppressive medications may have deterioration in kidney function and may develop end-stage renal failure. Nonspecific renal protective medicines, such as angiotensin-converting enzyme inhibitors, angiotensin 2 receptor blockers, and anti-lipid medications, slow the course of the illness. Recurrent focal segmental glomerulosclerosis in the allograft affects around a third of individuals who get a kidney transplant, and it frequently responds to a combination of plasma exchange, rituximab, and increased immunosuppression. Despite the fact that these results show a considerable improvement in outcome, further multicenter controlled studies are required to determine the optimum drugs and regimens to be used.