Early-onset pancreatic cancer and associated metabolic risk factors in the Middle East and North Africa: A 20-year analysis of the Global Burden of Disease Study.

BACKGROUND AND OBJECTIVE: Early-onset pancreatic cancer (EOPC) is associated with poor prognosis and high disease burden. Metabolic risk factors such as diabetes and obesity are considered risk factors of EOPC. Recently, there has been an increasing number of EOPCs worldwide. However, the analysis of EOPC, including its metabolic risk factors, in the Middle East and North Africa (MENA) region has not been fully addressed. METHODS: Data from the Global Burden of Disease Study between 2000 and 2019 was used to analyze the prevalence, incidence, deaths and disability-adjusted life years (DALYs) associated with EOPC and its metabolic risk factors. The analysis further categorized the data based on countries, income status and sex and examined the annual percentage change (APC). RESULTS: Approximately 2800 cases, 2400 deaths and 114,000 DALYs were attributable to EOPC in the MENA region. The incidence (APC + 3.42%), death (APC + 0.73%) and DALYs (APC + 3.23%) rates of EOPC increased. In addition, the death and DALY rates of EOPC attributable to obesity and diabetes increased. High and upper-middle-income countries exhibited a higher burden of EOPC than lower-income countries. CONCLUSION: Over the past two decades, the burden of EOPC and its associated metabolic risk factors has increased. There is an urgent need for region-wide policy development, including screening methods and risk factor reduction, to mitigate the high and rising burden of EOPC in the MENA region.

Disparities in metabolic dysfunction-associated steatotic liver disease and cardiometabolic conditions in low and lower middle-income countries: a systematic analysis from the global burden of disease study 2019.

OBJECTIVE: Metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiometabolic conditions affect populations across economic strata. Nevertheless, there are limited epidemiological studies addressing these diseases in low (LICs) and lower-middle-income countries (lower MICs). Therefore, an analysis of the trend of MASLD and cardiometabolic conditions in these countries is necessary. METHODS: From 2000 to 2019, jointpoint regression analysis was employed to calculate the prevalence, mortality, and disability-adjusted life years (DALYs) for cardiometabolic conditions including MASLD, type 2 diabetes mellitus (T2DM), dyslipidemia (DLP), hypertension (HTN), obesity, peripheral artery disease (PAD), atrial fibrillation and flutter (AF/AFL), ischemic heart disease (IHD), stroke, and chronic kidney disease from HTN and T2DM, in LICs and lower MICs (according to the World Bank Classification 2019) using the Global Burden of Disease 2019 data. RESULTS: Among the eleven cardiometabolic conditions, MASLD (533.65 million), T2DM (162.96 million), and IHD (76.81 million) had the highest prevalence in LICs and Lower MICs in 2019. MASLD represented the largest proportion of global prevalence in these countries (43 %). From 2000 to 2019, mortality in LICs and lower MICs increased in all cardiometabolic conditions, with obesity-related mortality having the highest increase (+134 %). During this timeframe, there were increased age-standardized death rates (ASDR) from obesity, PAD, and AF/AFL. From all conditions, the DALYs-to-prevalence ratio was higher in LICs and lower MICs than the global average. CONCLUSION: The burden of MASLD and cardiometabolic conditions is increasing worldwide, with LICs and lower MICs experiencing higher (DALYs) disability per prevalence. As these conditions are preventable, counteracting these trends requires not only the modification of ongoing actions but also the strategizing of immediate interventions.

Is it time for class I recommendation for sodium-glucose cotransporter-2 inhibitors in heart failure with mildly reduced or preserved ejection fraction?: An updated systematic review and meta-analysis.

Background: In heart failure with reduced ejection fraction (HFrEF), sodium-glucose cotransporter-2 (SGLT2) inhibitors were demonstrated to lower cardiovascular mortality (CV death) and hospitalization for heart failure (HHF); however, the advantages of SGLT2 inhibitors in heart failure with mildly reduced (HFmrEF) or preserved ejection fraction (HFpEF) are less clear. SGLT2 inhibitors were reported to enhance quality of life (QoL) in HFmrEF or HFpEF patients; however, the findings among studies are inconsistent. Objective: To conduct an updated systematic review and meta-analysis of recent data to assess the effect of SGLT2 inhibitors on cardiovascular outcomes and QoL in patients with HFmrEF or HFpEF. Method: Three databases were searched for studies that evaluated SGLT2 inhibitors and their effect on cardiovascular outcomes, including CV death, HHF, all-cause death, and the composite outcome of CV death, HHF, and urgent visit for heart failure (HF), and patient QoL (Kansas City Cardiomyopathy Questionnaire [KCCQ] score compared to baseline, and increase in KCCQ score ≥ 5 points) that were published during January 2000-August 2022. The meta-analysis was performed using the inverse variance method and random-effects model. INPLASY registration: INPLASY202290023. Results: Sixteen studies (9 recent RCTs) were included, and a total of 16,710 HFmrEF or HFpEF patients were enrolled. SGLT2 inhibitors significantly reduced composite cardiovascular outcome (CV death/HHF/urgent visit for HF; pooled hazard ratio [HR]: 0.80, 95% confidence interval [95%CI]: 0.74-0.86) and HHF alone (HR: 0.74, 95%CI: 0.67-0.82), but there was no significant reduction in CV death alone (HR: 0.93, 95%CI: 0.82-1.05). Benefit of SGLT2 inhibitors for decreasing CV death/HHF was observed across all subgroups, including left ventricular ejection fraction (LVEF) range, diabetes status, New York Heart Association functional class, and baseline renal function. For total HHF, SGLT2 inhibitors conferred benefit in both LVEF 50-60% (HR: 0.64, 95%CI: 0.54-0.76), and LVEF >60% (HR: 0.84, 95%CI: 0.71-0.98). Significant change was observed in the KCCQ-clinical summary score compared to baseline (mean difference: 1.33, 95%CI: 1.31-1.35), and meaningful improvement in QoL was shown across all 3 types of increase in KCCQ score ≥ 5 points. Conclusion: This study demonstrates the benefits of SGLT2 inhibitors for improving cardiovascular outcomes and QoL in HFmrEF or HFpEF patients.

Rare cause of neonatal apnea from congenital central hypoventilation syndrome.

BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare condition caused by mutations in the Paired-Like Homeobox 2B (PHOX2B) gene. It causes alveolar hypoventilation and autonomic dysregulation. This report aimed to raise awareness of this rare cause of neonatal apnea and hypoventilation as well as described the diagnostic work up to confirm the diagnosis in resource-limited setting where polysomnography for neonate is unavailable. CASE PRESENTATION: A late preterm female newborn born from a non-consanguineous primigravida 31-year-old mother had desaturation soon after birth followed by apnea and bradycardia. After becoming clinically stable, she still had extubation failure from apnea without hypercapnic ventilatory response which worsened during non-rapid eye movement (NREM) sleep. After exclusion of other etiologies, we suspected congenital central hypoventilation syndrome and sent genetic testing. The result showed a PHOX2B gene mutation which confirmed the diagnosis of CCHS. We gave the patient's caregivers multidisciplinary home respiratory care training including tracheostomy care, basic life support, and simulation training for respiratory problem solving. Then, the patient was discharged and scheduled for follow-up surveillance for associated conditions. CONCLUSION: Diagnosis of CCHS in neonates includes the main clue of the absence of hypercapnic ventilatory response which worsens during non-rapid eye movement (NREM) sleep after exclusion of other causes. Molecular testing for PHOX2B gene mutation was used to confirm the diagnosis.