Publications by authors named "Pappachan J"

Use of immunomodulating agents to prevent the progression of autoimmune β-cell damage leading to type 1 diabetes mellitus (T1DM) is an interesting area for research. These include non-specific anti-inflammatory agents, immunologic vaccination and anti-inflammatory agents targeting specific immune cells or cytokines. Teplizumab is an anti-CD3-molecule that binds to and leads to the disappearance of the CD3/TCR complex and rendering the T cell anergic to its target antigen.

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To describe the demographic and clinical characteristics of patients with Charcot neuro-osteoarthropathy (CNO) and to examine for differences between participants with Type 1 diabetes mellitus (DM) (T1DM) and Type 2 diabetes mellitus (T2DM). Multicenter observational study in eight diabetic foot clinics in six countries between January 1, 1996, and December 31, 2022. Demographic, clinical, and laboratory parameters were obtained from the medical records.

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Background: Endogenous glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) regulate islet cell function. GLP-1 receptor agonists (GLP-1RAs) have been associated with an elevated risk of acute pancreatitis. Data on the pancreatic safety of tirzepatide (a dual GLP-1 and GIP agonist) and its effects on islet cell function in randomized controlled trials (RCTs) are scarce.

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Background: Peripheral oxygen saturation (SpO) above 94% is typical in children in paediatric intensive critical care units (PICUs) who are receiving invasive ventilation and supplemental oxygen. In a previous report from the Oxy-PICU trial, we showed that lower (conservative) oxygenation targets (SpO 88-92%) are beneficial, showing small but statistically significant differences in duration of organ support and large but non-significant cost reductions at 30 days. In this pre-specified analysis of the Oxy-PICU trial, we compare longer-term outcomes and cost-effectiveness of conservative versus liberal (SpO >94%) oxygenation targets in children with emergency PICU admission.

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Bariatric interventions have shown the best therapeutic benefits in individuals with obesity. They can be classified into surgical procedures (bariatric/metabolic surgery) and endoscopic procedures. Common surgical procedures include sleeve gastrectomy, Roux-en-Y gastric bypass, bilio-pancreatic diversion with or without duodenal switch and Stomach Intestinal Pylorus Sparing Surgery.

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Article Synopsis
  • The hormonal changes during the perimenopausal period can lead to various health issues for women, including decreased well-being, psychological distress, and reduced quality of life.
  • Common symptoms experienced during menopause are hot flashes, changes in sleep and mood, fatigue, weight gain, and urogenital issues; mood swings and sleep disruptions are often overlooked but can greatly impact productivity and mental health.
  • Effective management of these symptoms should take a personalized approach, considering the benefits and risks of hormone replacement therapy (HRT), with recent research highlighting its potential role in improving mood and sleep quality for menopausal women.
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Acute lung Injury leads to alterations in surfactant lipid composition and metabolism. Although several mechanisms contribute to dysregulated surfactant metabolism, studies investigating in vivo surfactant metabolism are limited. The aim of this study is to characterise surfactant phospholipid composition and flux utilising a stable isotope labelling technique in mechanically ventilated paediatric patients.

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Article Synopsis
  • - The study explored the feasibility of using high-flow humidified oxygen (HiFlo) as a treatment for children aged 2-11 with acute severe asthma (ASA) who did not respond to standard inhaled bronchodilator treatment.
  • - In a randomized controlled trial involving 56 children, those receiving HiFlo experienced a lower treatment failure rate (64%) compared to the standard care group (86%), and they also had a faster time to meet hospital discharge criteria (29.3 hours vs. 36.8 hours).
  • - The findings suggest that HiFlo could be a promising intervention for childhood ASA, warranting a larger definitive trial to evaluate its effectiveness despite the initial lack of evidence.
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Background: Diabesity (diabetes as a consequence of obesity) has emerged as a huge healthcare challenge across the globe due to the obesity pandemic. Judicious use of antidiabetic medications including semaglutide is important for optimal management of diabesity as proven by multiple randomized controlled trials. However, more real-world data is needed to further improve the clinical practice.

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Diabetic cardiomyopathy (DbCM) is a common but underrecognized compli-cation of patients with diabetes mellitus (DM). Although the pathobiology of other cardiac complications of diabetes such as ischemic heart disease and cardiac autonomic neuropathy are mostly known with reasonable therapeutic options, the mechanisms and management options for DbCM are still not fully understood. In its early stages, DbCM presents with diastolic dysfunction followed by heart failure (HF) with preserved ejection fraction that can progress to systolic dysfunction and HF with reduced ejection fraction in its advanced stages unless appropriately managed.

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  • Metabolic dysfunction-associated steatotic liver disease (MASLD) poses significant health risks, leading to liver disease and cardiovascular issues, prompting studies on effective treatments like Resmetirom, a thyroid hormone receptor-β agonist.
  • A systematic review analyzed random controlled trials comparing Resmetirom to placebo, identifying four low-bias studies involving 2,359 participants, with notable improvements in liver fat content and lipid profiles after treatment.
  • Resmetirom effectively reduced liver fat and improved other metabolic parameters without significant increases in adverse events compared to placebo, suggesting it is a promising option for managing MASLD.
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Tuberculosis (TB) remains a huge global healthcare challenge even in the 21 century though the prevalence has dropped in developed countries in recent decades. Diabetes mellitus (DM) is an important risk factor for the development and perpetuation of TB owing to the immune dysfunction in patients with DM. The coexistence of both diseases in the same individual also aggravates disease severity, complications, and chance of treatment failure because of gross immune alterations posed by DM as well as TB.

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Objectives: A conservative oxygenation strategy, targeting peripheral oxygen saturations (Sp o2 ) between 88% and 92% in mechanically ventilated children in PICU, was associated with a shorter duration of organ support and greater survival compared with Sp o2 greater than 94% in our recent Oxy-PICU trial. Sp o2 monitors may overestimate arterial oxygen saturation (Sa o2 ) in patients with higher levels of skin pigmentation compared with those with less skin pigmentation. We investigated if ethnicity was associated with changes in distributions of Sp o2 and F io2 and outcome.

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Article Synopsis
  • * This type of diabetes includes conditions like maturity-onset diabetes of the young (MODY) and neonatal diabetes mellitus (NDM), each requiring different diagnostic approaches and genetic testing methods.
  • * Ongoing research aims to improve genetic testing and develop gene-based therapies, which could enhance precision medicine and deepen understanding of diabetes mechanisms, as highlighted in a recent clinical review.
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The global obesity pandemic has resulted in a rise in the prevalence of male obesity-related secondary hypogonadism (MOSH) with emerging evidence on the role of testosterone therapy. We aim to provide an updated and practical approach towards its management. We did a comprehensive literature search across MEDLINE ( PubMed), Scopus, and Google Scholar databases using the keywords "MOSH" OR "Obesity-related hypogonadism" OR "Testosterone replacement therapy" OR "Selective estrogen receptor modulator" OR "SERM" OR "Guidelines on male hypogonadism" as well as a manual search of references within the articles.

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Sodium glucose cotransporter-2 inhibitors (SGLT-2i) are antidiabetic medications with remarkable cardiovascular (CV) benefits proven by multiple randomised controlled trials and real-world data. These drugs are also useful in the prevention of CV disease (CVD) in patients with diabetes mellitus (DM). Although DM as such is a huge risk factor for CVD, the CV benefits of SGLT-2i are not just because of antidiabetic effects.

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There has been an exponential increase in the global prevalence of fatty liver disease in recent years in association with the obesity pandemic worldwide. 'Metabolic dysfunction-associated fatty liver disease', the new terminology adopted by an international panel of experts in 2020 to largely replace the old term 'non-alcoholic fatty liver disease', has now been accepted by most hepatologists and diabetologists across the globe. The term metabolic dysfunction-associated fatty liver disease was created to better reflect the metabolicand liver-specific manifestations and complications of fatty liver disease.

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Childhood-onset obesity has emerged as a major public healthcare challenge across the globe, fueled by an obesogenic environment and influenced by both genetic and epigenetic predispositions. This has led to an exponential rise in the incidence of type 2 diabetes mellitus in children and adolescents. The looming wave of diabetes-related complications in early adulthood is anticipated to strain the healthcare budgets in most countries.

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Pheochromocytomas and paragangliomas (PPGLs) have emerged as one of the most common endocrine tumors. It epitomizes fascinating crossroads of genetic, metabolic, and endocrine oncology, providing a canvas to explore the molecular intricacies of tumor biology. Predominantly rooted in the aberration of metabolic pathways, particularly the Krebs cycle and related enzymatic functionalities, PPGLs manifest an intriguing metabolic profile, highlighting elevated levels of oncometabolites like succinate and fumarate, and furthering cellular malignancy and genomic instability.

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Despite the advent of relatively reliable modalities of diagnosing diabetic peripheral neuropathy (DPN), such as nerve conduction studies, there is still a knowledge gap about the pathophysiology, and thus limited available interventions for symptom control and curtailing disease progression. The pharmacologic aspect of management is mainly centred on pain control, however, there are several important aspects of DPN such as loss of vibration sense, pressure sense, and proprioception which are associated with risks to lower limb health, which pharmacotherapy does not address. Furthermore, published evidence suggests non-pharmacologic interventions such as glycaemic control through dietary modification and exercise need to be combined with other measures such as psychotherapy, to reach a desired, however modest effect.

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Background: Sodium glucose cotransporter-2 inhibitors (SGLT-2i) are a class of drugs with modest antidiabetic efficacy, weight loss effect, and cardiovascular benefits as proven by multiple randomised controlled trials (RCTs). However, real-world data on the comparative efficacy and safety of individual SGLT-2i medications is sparse.

Aim: To study the comparative efficacy and safety of SGLT-2i using real-world clinical data.

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