Optimizing Cardiovascular Outcomes in Type 2 Diabetes: Early Initiation of Dapagliflozin and Sitagliptin From a Cardiologist's Perspective.

Introduction: Cardiovascular (CV) disease (CVD) risk is greater in patients with diabetes mellitus and is the major contributor to disability and premature mortality compared to those who do not have diabetes. The clinical implications of CVD in people with type 2 diabetes mellitus (T2DM) have increased the emphasis on concurrent treatment to prevent the onset of CVD through personalized management for glycemic control and CVD risk management.

Methods: Key opinion leaders, comprising 98 cardiologists from across India, participated in seven advisory board meetings held in various cities to explore the challenges and strategies for the early initiation of fixed-dose combinations (FDCs) of sodium-glucose co-transporter-2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP4i) with a focus on the combination of dapagliflozin and sitagliptin in addressing the CVD risks in patients with T2DM and high risk for CV complications.

Rare Presentation of Eosinophilic Cholangitis in a 32-Year-Old Man.

Eosinophilic cholangitis (EC) is a rare condition characterized by eosinophilic infiltration of the bile ducts, often mimicking diseases like primary sclerosing cholangitis or cholangiocarcinoma. We report the case of a 32-year-old man with severe epigastric pain and elevated liver function tests. Initial imaging revealed common bile duct dilation and multiple strictures, initially suggestive of primary sclerosing cholangitis.

Digital Twin Technology in Resolving Polycystic Ovary Syndrome and Improving Metabolic Health: A Comprehensive Case Study.

Background: Clinical manifestations of polycystic ovary syndrome (PCOS) are heterogeneous, with hallmarks including anovulation, androgen excess, and insulin resistance.

Case Report: A 38-year-old female with typical PCOS features presented with hypertension, obesity, and elevated fasting and postprandial insulin levels. She was enrolled in the Digital Twin (DT) platform, which uses artificial intelligence and Internet of Things to deliver personalized nutrition by predicting postprandial glucose responses and suggesting alternative foods with lower postprandial glucose response through a mobile app.

Negative allosteric modulation of CB cannabinoid receptor signaling suppresses opioid-mediated tolerance and withdrawal without blocking opioid antinociception.

The direct blockade of CB cannabinoid receptors produces therapeutic effects as well as adverse side-effects that limit their clinical potential. CB negative allosteric modulators (NAMs) represent an indirect approach to decrease the affinity and/or efficacy of orthosteric cannabinoid ligands or endocannabinoids at CB. We recently reported that GAT358, a CB-NAM, blocked opioid-induced mesocorticolimbic dopamine release and reward via a CB-allosteric mechanism of action.

Negative allosteric modulation of cannabinoid CB receptor signaling suppresses opioid-mediated tolerance and withdrawal without blocking opioid antinociception.

Unlabelled: The direct blockade of CB cannabinoid receptors produces therapeutic effects as well as adverse side-effects that limit their clinical potential. CB negative allosteric modulators (NAMs) represent an indirect approach to decrease the affinity and/or efficacy of orthosteric cannabinoid ligands or endocannabinoids at CB . We recently reported that GAT358, a CB -NAM, blocked opioid-induced mesocorticolimbic dopamine release and reward via a CB -allosteric mechanism of action.

Pilot Study on Gut Microbiota Profile in Indian Children with Type 1 Diabetes.

Background: Non-genetic factors like microbial dysbiosis may be contributing to the increasing incidence/progression of type 1 diabetes mellitus (T1DM).

Objectives: To analyse the gut microbiota profile in Indian children with T1DM and its effect on glycaemic control.

Methodology: Faecal samples of 29 children with T1DM were collected and faecal microbial DNA was extracted and subjected to 16S rRNA (ribosomal RNA) sequencing and further analysis.

Iliac Artery-Inferior Vena Cava-Duodenal Fistula: An Unusual Cause of Massive Gastrointestinal Bleeding.

An arteriovenous-enteric fistula is a 3-way connection between the vascular and enteric system and associated with high mortality. We describe a case of iliac artery-inferior vena cava-duodenal fistula in a young female with a retroperitoneal mass presenting with sepsis and hemorrhagic shock with a catastrophic clinical course. These fistulas can be missed on endoscopy/colonoscopy and are usually diagnosed on computed tomography angiogram of the abdomen.

GAT107-mediated α7 nicotinic acetylcholine receptor signaling attenuates inflammatory lung injury and mortality in a mouse model of ventilator-associated pneumonia by alleviating macrophage mitochondrial oxidative stress via reducing MnSOD-S-glutathionylation.

Supraphysiological concentrations of oxygen (hyperoxia) can compromise host defense and increase susceptibility to bacterial and viral infections, causing ventilator-associated pneumonia (VAP). Compromised host defense and inflammatory lung injury are mediated, in part, by high extracellular concentrations of HMGB1, which can be decreased by GTS-21, a partial agonist of α7 nicotinic acetylcholine receptor (α7nAChR). Here, we report that a novel α7nAChR agonistic positive allosteric modulator (ago-PAM), GAT107, at 3.

Effect of cigarette smoking on serum anti-Mullerian hormone and antral follicle count in women seeking fertility treatment: a prospective cross-sectional study.

Objectives: The relationship between smoking and ovarian reserve markers is inconclusive. The primary objective of our study was to assess the effect of cigarette smoking on the quantitative ovarian reserve parameters, serum anti-Mullerian hormone (AMH) and antral follicle count (AFC) as relevant to prediction of fertility outcomes in women seeking fertility treatment. Our secondary aims were to validate self-reported smoking behaviour using biomarkers and evaluate the association between biomarkers of ovarian reserve (serum AMH and AFC) with biomarkers of smoking exposure (breath carbon monoxide (CO) and urine cotinine levels).

Reexamining the optimal nuchal translucency cutoff for diagnostic testing in the cell-free DNA and microarray era: results from the Victorian Perinatal Record Linkage study.

Background: The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine recently recommended offering genetic counseling and diagnostic testing for enlarged nuchal translucency at ≥3.0 mm, regardless of previous negative screening with noninvasive prenatal testing.

Objective: This study aimed to perform a population-based, individual record linkage study to determine the optimal definition of an enlarged nuchal translucency for the detection of atypical chromosome abnormalities.

The Positive Allosteric Modulation of alpha7-Nicotinic Cholinergic Receptors by GAT107 Increases Bacterial Lung Clearance in Hyperoxic Mice by Decreasing Oxidative Stress in Macrophages.

Supplemental oxygen therapy with supraphysiological concentrations of oxygen (hyperoxia; >21% O) is a life-saving intervention for patients experiencing respiratory distress. However, prolonged exposure to hyperoxia can compromise bacterial clearance processes, due to oxidative stress-mediated impairment of macrophages, contributing to the increased susceptibility to pulmonary infections. This study reports that the activation of the α7 nicotinic acetylcholine receptor (α7nAChR) with the delete allosteric agonistic-positive allosteric modulator, GAT107, decreases the bacterial burden in mouse lungs by improving hyperoxia-induced lung redox imbalance.

A minimum estimate of the prevalence of 22q11 deletion syndrome and other chromosome abnormalities in a combined prenatal and postnatal cohort.

Study Question: What is the frequency of major chromosome abnormalities in a population-based diagnostic data set of genomic tests performed on miscarriage, fetal and infant samples in a state with >73 000 annual births?

Summary Answer: The overall frequency of major chromosome abnormalities in the entire cohort was 28.2% (2493/8826), with a significant decrease in the detection of major chromosome abnormalities with later developmental stage, from 50.9% to 21.

RIC3, the cholinergic anti-inflammatory pathway, and neuroinflammation.

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels having many functions including inflammation control, as part of the cholinergic anti-inflammatory pathway. Genome wide association studies implicated RIC3, a chaperone of nAChRs, in multiple sclerosis (MS), a neuroinflammatory disease. To understand the involvement of RIC3 in inflammatory diseases we examined its expression, regulation, and function in activated immune cells.

Incidence and risk factors for post-operative mortality, hospitalization, and readmission rates following pancreatic cancer resection.

Background: The only potentially curative approach for pancreatic cancer is surgical resection, but this technically challenging procedure carries risks for postoperative morbidities and mortality. This study of a large, contemporary national database illustrates incidences of, and risk factors for, post-procedural mortality, prolonged hospital stay, and 30-day readmission.

Methods: From the National Cancer Database (NCDB), stage I-III pancreatic adenocarcinomas were identified [2004-2015].

Association between timing of diagnosis of trisomy 21, 18, and 13 and maternal socio-economic status in Victoria, Australia: A population-based cohort study from 2015 to 2016.

Objectives: To explore the association between timing of diagnosis of common autosomal trisomies, maternal age, and socio-economic status (SES).

Design: Retrospective study of cytogenetic diagnoses of trisomy 21 (T21), trisomy 18 (T18), and trisomy 13 (T13) in Victoria, Australia, in 2015 to 2016, stratified by timing (prenatal less than 17 weeks gestation, prenatal including or greater than or 17 weeks gestation, and postnatal before 12 months of age), maternal age, and SES region. Utilisation of prenatal testing following a live-born T21 infant was ascertained via record linkage.

Distal Ileal Ulcers as Gastrointestinal Manifestation of Waldenstrom Macroglobulinemia.

Waldenstrom macroglobulinemia (WM) is a neoplastic disorder of the B-cell lymphoid system. A 69-year-old man with WM presented with diarrhea for 6 months. Magnetic resonance enterography showed thickening of the terminal ileum (TI).

Survival Trends for Resectable Pancreatic Cancer Using a Multidisciplinary Conference: the Impact of Post-operative Chemotherapy.

Purpose: Despite advances in various treatment modalities, surgical resection for pancreatic ductal adenocarcinoma (PDA) remains the only curative treatment. Data remains limited regarding survival rates for resectable PDA when managed by a multidisciplinary pancreas conference (MDPC). The aim of this study is to assess survival rates, identify significant predictors of mortality, and assess the benefits of adjuvant chemotherapy for resectable PDA following presentation at a MDPC.

Time to Adjuvant Systemic Therapy Following Pancreatic Cancer Resection and Effect on Outcome.

Objectives: The appropriate timing of chemotherapy following surgery for resectable pancreatic adenocarcinoma is controversial. Using the National Cancer Database we evaluated time to initiation of chemotherapy postresection and correlated with outcome.

Methods: We identified stage I-III pancreatic adenocarcinoma treated surgically with adjuvant chemoradiotherapy.

Defining Pancreatitis as a Risk Factor for Pancreatic Cancer: The Role, Incidence, and Timeline of Development.

Objectives: Acute and/or chronic pancreatitis has been implicated as an important risk factor for pancreatic cancer; however, the incidence and temporal relationship of pancreatitis before pancreatic cancer diagnosis are unclear. We aim to understand the role and incidence of pancreatitis temporally with the development of pancreatic cancer.

Methods: A population-based study was used to investigate a temporal relationship between pancreatitis and pancreatic cancer diagnoses.

A Case of Secondary Sclerosing Cholangitis in the setting of Non-Hodgkin's Lymphoma.

Sclerosing cholangitis represents a spectrum of cholestatic liver disease characterized by inflammation, fibrosis, and stricture of the bile ducts. A 67-year-old Caucasian female with a history of breast cancer in remission, presented with jaundice and an exophytic mass at the base of the tongue. Laboratory data revealed cholestasis with alkaline phosphatase 953 U/L, total bilirubin 7.