Glucagon-Like Peptide-1 Receptor Agonists and Major Adverse Cardiovascular Events in Patients With and Without Diabetes: A Meta-Analysis of Randomized-Controlled Trials.

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown encouraging results regarding cardiovascular outcomes mainly in patients with diabetes. In the present study, we compared the efficacy of GLP-1 RAs in cardiovascular events between patients with and without diabetes. METHODS: After finding eligible studies assessing the impact of GLP-1 RAs on cardiovascular events in patients with and without diabetes using a systematic search, we performed a meta-analysis on randomized-controlled trials (RCTs) comparing cardiovascular outcomes between patients taking GLP-1 RAs and placebo stratified by the presence or absence of diabetes. Relative risk (RR) and its 95% confidence interval (CI) were set as the reporting effect size using the random-effects model. RESULTS: A total of 24 RCTs (50 033 with GLP-1 RAs and 44 514 with placebo) were included. Patients on GLP-1 RAs had lower risk of major adverse cardiovascular events (MACE) (RR 0.87, 95% CI 0.82-0.93), cardiovascular death (RR 0.88, 95% CI 0.82-0.94), myocardial infarction (MI) (RR 0.87, 95% CI 0.77-0.97), stroke (RR 0.86, 95% CI 0.80-0.92), and hospitalization for heart failure (RR 0.90, 95% CI 0.83-0.98). Both subgroups were shown to be effective in terms of MACE and mortality. Nondiabetic patients had decreased risk of hospitalization for heart failure and MI, whereas the diabetic subgroup had marginally nonsignificant efficacy. CONCLUSION: The findings of this meta-analysis indicated that patients who are overweight/obese but do not have diabetes have a comparable reduction in the risk of adverse cardiovascular events as those with diabetes. These results need to be confirmed further by large-scale randomized trials in the future.

Algorithmic Approach to Benign Prostatic Hyperplasia: An Indian Perspective.

Benign prostatic hyperplasia (BPH) is a prevalent condition affecting aging men, necessitating a comprehensive and evidence-based approach to diagnosis and management. This manuscript, through the summarization of the latest evidence, aims to establish a consensus among clinicians regarding optimal strategies for diagnosing and managing BPH, to improve patient care and outcomes in clinical practice. A panel of urologists conducted a comprehensive review of the literature by searching various databases and search engines (PubMed, Google Scholar, and Cochrane databases). They identified relevant studies on the diagnosis and management of BPH. The literature was summarized and analyzed to develop 14 statements. The panel utilized a Delphi methodology over two rounds (R1 and R2) to reach a consensus on the statements, considering both the literature evidence and expert opinions. The expert panel reached a consensus on 14 statements addressing diverse aspects of BPH, including tailored therapies for different patient profiles and the necessity for a unified diagnosis and management algorithm to enhance patient outcomes. In conclusion, a unified approach to diagnosing and managing BPH promotes consistent and effective patient care. Proper drug selection, considering factors like efficacy and patient-specific characteristics, is crucial for managing BPH. This approach optimizes treatment outcomes and improves the quality of life for BPH patients.

Effects of States' Methods for Estimating Nonfatal Overdose, United States, 2021.

OBJECTIVE: Previous nonfatal overdose is a key risk factor for drug overdose death; however, current nonfatal overdose surveillance is limited to people who receive medical attention. We identified states that tracked nonfatal overdoses treated in prehospital and hospital care settings, assessed the effects of different surveillance methods on the magnitude of nonfatal overdose estimates, and estimated states' nonfatal-to-fatal overdose ratio. METHODS: Two analysts independently reviewed state websites to characterize states' methods of capturing nonfatal overdose events from December 2022 through February 2023. We collected information on surveillance methods in 5 states that met the inclusion criteria, including data source, measure specification, drug(s) involved, and whether states performed deduplication or published mutually exclusive measure specifications to capture unique events across care settings. We calculated nonfatal-to-fatal overdose ratios to assess the effects of different data sources on estimates of nonfatal overdoses. RESULTS: Illinois, Maine, North Carolina, and West Virginia used syndromic surveillance data and New Jersey used hospital discharge data to track nonfatal overdose-related emergency department visits. Illinois and West Virginia tracked nonfatal overdose-related encounters with emergency medical services. Other states tracked opioid overdoses reversed following naloxone administration by emergency medical services, law enforcement, and community members. Maine, New Jersey, and West Virginia published nonfatal overdose information by using mutually exclusive measure specifications; the number of nonfatal overdoses per fatal overdose in these states ranged from approximately 5:1 to 14:1. PRACTICE IMPLICATIONS: Establishing a standard framework to combine data from existing national surveillance systems in prehospital and hospital care settings can improve nonfatal overdose estimates and enable comparisons between jurisdictions to help decision makers identify areas most in need of essential services.

Nonsterile Process for Biohydrogen Production: Recent Updates, Challenges, and Opportunities.

Hydrogen (H2), a clean and versatile energy carrier, has recently gained significant attention as a potential solution for reducing carbon emissions and promoting sustainable energy systems. The yield and efficiency of the biological H2 production process primarily depend on sterilization conditions. Various strategies, such as heat inactivation and membrane-based sterilization, have been used to achieve desirable yields via microbial fermentation. Almost every failed biotransformation process is linked to nonsterile conditions at any reaction stage. Therefore, the production of renewable biofuels as alternatives to fossil fuels is more attractive. Pure sugars have been widely documented as a costly feedstock for H2 production under sterile conditions. Biotransformation under nonsterile conditions is more desirable for stable and sustainable operation. Low-cost feeds, such as biowaste, are considered suitable alternatives, but they require appropriate sterilization to overcome the limitations of inherited or contaminating microbes during H2 production. This article describes the status of microbial fermentative processes for H2 production under nonsterile conditions and discusses strategies to improve such processes for sustainable, cleaner production.

Association between sleep duration and hypertension incidence: Systematic review and meta-analysis of cohort studies.

AIM: Sleep duration has been suggested to be associated with hypertension (HTN). However, evidence of the nature of the relationship and its direction has been inconsistent. Therefore, we performed a meta-analysis to assess the relationship between sleep duration and risk of HTN incidence, and to distinguish more susceptible populations. METHODS: PubMed, Embase, Scopus, Web of Science, and ProQuest were searched from January 2000 to May 2023 for cohort studies comparing short and long sleep durations with 7-8 hours of sleep for the risk of HTN incidence. Random-effect model (the DerSimonian-Laird method) was applied to pool risk ratios (RR) and 95% confidence interval (CI). RESULTS: We included sixteen studies ranging from 2.4 to 18 years of follow-up duration evaluating HTN incidence in 1,044,035 people. Short sleep duration was significantly associated with a higher risk of developing HTN (HR: 1.07, 95% CI: 1.06-1.09). The association was stronger when the sleep duration was less than 5 hours (HR: 1.11, 95% CI: 1.08-1.14). In contrast to males, females (HR: 1.07, 95% CI: 1.04-1.09) were more vulnerable to developing HTN due to short sleep duration. No significant difference between different follow-up durations and age subgroups was observed. Long sleep duration was not associated with an increased incidence of HTN. CONCLUSION: Short sleep duration was associated with higher risk of HTN incidence, however, there was no association between long sleep duration and incidence of HTN. These findings highlight the importance of implementing target-specific preventive and interventional strategies for vulnerable populations with short sleep duration to reduce the risk of HTN.

Case Report: Scorpion Envenomation with Delayed Ischemic Priapism in a Preadolescent-An Unusual Presentation.

Priapism as a complication of scorpionism in children is rare and is categorized as grade II of severity. The pathogenesis is the activation of parasympathetic pathways that stimulate the release of acetylcholine. An 8-year-old boy, a known case of steroid-dependent nephrotic syndrome, presented with a history of persistent penile erection for the previous 12 hours. He had a history of a black scorpion (Heterometrus swammerdami) sting on his right leg 4 days earlier. He was given adequate analgesia, and prazosin was started at 30 µg/kg/dose because of the parasympathetic overactivity. Doppler ultrasonography of the penile shaft showed a bilateral thickened, bulky, and edematous corpus cavernosa and no arterial flow due to venous congestion, suggesting ischemic (low-flow) priapism. Detumescence was not accomplished with saline irrigation and aspiration or with intracorporeal irrigation with phenylephrine. Thus, a distal T-shunt was done. We illustrate an interesting case of scorpion envenomation with delayed ischemic priapism.

Novel cofactor regeneration-based magnetic metal-organic framework for cascade enzymatic conversion of biomass-derived bioethanol to acetoin.

Upgrading biomass-derived bioethanol to higher-order alcohols using conventional biotechnological approaches is challenging. Herein, a novel, magnetic metal-organic-framework-based cofactor regeneration system was developed using ethanol dehydrogenase (EtDH:D46G), NADH oxidase (NOX), formolase (FLS:L482S), and nicotinamide adenine dinucleotide (NAD+) for converting rice straw-derived bioethanol to acetoin. A magnetic zeolitic imidazolate framework-8@Fe3O4/NAD+ (ZIF-8@Fe3O4/NAD+) regeneration system for cell-free cascade reactions was introduced and used to encapsulate EtDH:D46G, NOX, and FLS:L482S (ENF). ZIF-8@Fe3O4/NAD+ENF created an efficient microenvironment for three-step enzyme cascades. Under the optimized conditions, the yield of acetoin from 100 mM bioethanol using ZIF-8@Fe3O4/NAD+ENF was 90.4 %. The regeneration system showed 97.1 % thermostability at 50 °C. The free enzymes retained only 16.3 % residual conversion, compared with 91.2 % for ZIF-8@Fe3O4/NAD+ENF after ten cycles. The magnetic metal-organic-framework-based cofactor regeneration system is suitable for enzymatic cascade biotransformations and can be extended to other cascade systems for potential biotechnological applications.

A mechanistic study on the tolerance of PAM distal end mismatch by SpCas9.

The therapeutic application of CRISPR-Cas9 is limited due to its off-target activity. To have a better understanding of this off-target effect, we focused on its mismatch-prone PAM distal end. The off-target activity of SpCas9 depends directly on the nature of mismatches, which in turn results in deviation of the active site of SpCas9 due to structural instability in the RNA-DNA duplex strand. In order to test the hypothesis, we designed an array of mismatched target sites at the PAM distal end and performed in vitro and cell line-based experiments, which showed a strong correlation for Cas9 activity. We found that target sites having multiple mismatches in the 18th to 15th position upstream of the PAM showed no to little activity. For further mechanistic validation, Molecular Dynamics simulations were performed, which revealed that certain mismatches showed elevated root mean square deviation values that can be attributed to conformational instability within the RNA-DNA duplex. Therefore, for successful prediction of the off-target effect of SpCas9, along with complementation-derived energy, the RNA-DNA duplex stability should be taken into account.

Pathophysiology, diagnosis and management of right ventricular failure: A state of the art review of mechanical support devices.

The function of the right ventricle (RV) is to drive the forward flow of blood to the pulmonary system for oxygenation before returning to the left ventricle. Due to the thin myocardium of the RV, its function is easily affected by decreased preload, contractile motion abnormalities, or increased afterload. While various etiologies can lead to changes in RV structure and function, sudden changes in RV afterload can cause acute RV failure which is associated with high mortality. Early detection and diagnosis of RV failure is imperative for guiding initial medical management. Echocardiographic findings of reduced tricuspid annular plane systolic excursion (<1.7) and RV wall motion (RV S' <10 cm/s) are quantitatively supportive of RV systolic dysfunction. Medical management commonly involves utilizing diuretics or fluids to optimize RV preload, while correcting the underlying insult to RV function. When medical management alone is insufficient, mechanical circulatory support (MCS) may be necessary. However, the utility of MCS for isolated RV failure remains poorly understood. This review outlines the differences in flow rates, effects on hemodynamics, and advantages/disadvantages of MCS devices such as intra-aortic balloon pump, Impella, centrifugal-flow right ventricular assist devices, extracorporeal membrane oxygenation, and includes a detailed review of the latest clinical trials and studies analyzing the effects of MCS devices in acute RV failure.

Incidence, Predictors, and Outcomes of Venous and Arterial Thrombosis in COVID-19: A Nationwide Inpatient Analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is known to increase the risk of venous thromboembolism (VTE) and arterial thromboembolism (ATE). However, the incidence, predictors, and outcomes of clinical thrombosis for inpatients with COVID-19 are not well known. This study aimed to enhance our understanding of clinical thrombosis in COVID-19, its associated factors, and mortality outcomes. METHOD: Hospitalised adult (≥18 years of age) patients with COVID-19 in 2020 were retrospectively identified from the US National Inpatient Sample database. Clinical characteristics, incident VTE, ATE, and in-hospital mortality outcomes were recorded. Multivariable logistic regression was performed to identify clinical factors associated with thrombosis and in-hospital mortality in COVID-19 inpatients. RESULTS: A total of 1,583,135 adult patients with COVID-19 in the year 2020 were identified from the National Inpatient Sample database; patients with thrombosis were 41% females with a mean age of 65.4 (65.1-65.6) years. The incidence of thrombosis was 6.1% (97,185), including VTE at 4.8% (76,125), ATE at 3.0% (47,790), and the in-hospital mortality rate was 13.4% (212,785). Patients with thrombosis were more likely to have respiratory symptoms of COVID-19 (76.7% vs 75%, p<0.001) compared with patients without thrombosis. The main factors associated with overall thrombosis, VTE, and ATE were paralysis, ventilation, solid tumours without metastasis, metastatic cancer, and acute liver failure. Although all thrombosis categories were associated with higher in-hospital mortality for COVID-19 inpatients in univariable analyses (p<0.001), they were not in multivariable analyses-thrombosis (odds ratio [OR] 1.24; 95% confidence interval [CI] 0.90-1.70; p=0.19), VTE (OR 0.70; 95% CI 0.52-1.00; p=0.05), and ATE (OR 1.07; 95% CI 0.92-1.25; p=0.36). CONCLUSIONS: The association of COVID-19 with thrombosis and VTE increases with increasing severity of the COVID-19 disease. Risk stratification of thrombosis is crucial in COVID-19 patients to determine the necessity of thromboprophylaxis.

Pragmatic Evaluation of Growth Hormone Stimulation Tests in Short Stature.

Introduction: To assess the performance of growth hormone stimulation tests (GHSTs) in the evaluation of short stature. Methods: It was a single-centre retrospective study carried out in children evaluated for short stature between January 2005 to March 2020. The clonidine stimulation test (CST) and glucagon stimulation test (GST) were used to assess growth hormone (GH) reserve (GST was performed only when peak GH levels were between 5 to ≤10 ng/mL on CST). A GH level of <5 ng/mL on CST or ≤10 ng/ml on both was used to corroborate GH deficiency. Results: A total of 556 children were eligible for this study. The mean (SD) age was 12.9 (3.5) years, and 66.3% were male. The peak GH level [median (IQR)] was 5.50 ng/ml (1.90 - 7.50) on CST (at 60 minutes) and 7.45 ng/ml (2.15 - 10.77) on GST (at 120 minutes). On restricting sampling to two time points, the false positive rate was 13.6% on CST (60, 90 minutes) and 11.5% on GST (120, 150 minutes). Similarly, restricting to three time points was associated with a false positive rate of 8.5% on CST (60, 90, 120 minutes) and 3.8% on GST (90, 120, 150 minutes). Using the treating clinician-determined diagnosis of GHD as a reference standard, the optimal cut-off of peak GH on CST was 7.79 ng/ml (sensitivity: 83.8%; specificity: 89.4%). Conclusion: Restricting the GH sampling to fewer time points is associated with an increase in the false positivity rate (FPR).

Harnessing the power of hybrid deep learning algorithm for the estimation of global horizontal irradiance.

Accurately and precisely estimating global horizontal irradiance (GHI) poses significant challenges due to the unpredictable nature of climate parameters and geographical limitations. To address this challenge, this study proposes a forecasting framework using an integrated model of the convolutional neural network (CNN), long short-term memory (LSTM), and gated recurrent unit (GRU). The proposed model uses a dataset of four different districts in Rajasthan, each with unique solar irradiance patterns. Firstly, the data was preprocessed and then trained with the optimized parameters of the standalone and hybrid models and compared. It can be observed that the proposed hybrid model (CNN-LSTM-GRU) consistently outperformed all other models regarding Mean absolute error (MAE) and Root mean squared error (RMSE). The experimental results demonstrate that the proposed method forecasts accurate GHI with a RMSE of 0.00731, 0.00730, 0.00775, 0.00810 and MAE of 0.00516, 0.00524, 0.00552, 0.00592 for Barmer, Jaisalmer, Jodhpur and Bikaner respectively. This indicates that the model is better at minimizing prediction errors and providing more accurate GHI estimates. Additionally, the proposed model achieved a higher coefficient of determination (R (Ghimire et al., 2019)), suggesting that it best fits the dataset. A higher R2 value signifies that the proposed model could explain a significant portion of the variance in the GHI dataset, further emphasizing its predictive capabilities. In conclusion, this work demonstrates the effectiveness of the hybrid algorithm in improving adaptability and enhancing prediction accuracy for GHI estimation.

An update on the safety of lanreotide autogel for the treatment of patients with neuroendocrine tumors.

INTRODUCTION: Neuroendocrine neoplasms (NENs) are a rare group of tumors originating from neuroendocrine cells in various organs. They include neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs), which differ in biological behavior and prognosis. NETs are usually well-differentiated and slow-growing, while NECs are poorly differentiated and more aggressive. Management of NETs often involves somatostatin analogs like octreotide and lanreotide to control tumor growth and alleviate symptoms, especially in well-differentiated NETs. Lanreotide is used to control tumor growth, and both lanreotide and octreotide alleviate symptoms. Treatment approaches may vary depending on the specific type and grade of the neuroendocrine neoplasm. AREAS COVERED: This review provides an update on the safety of lanreotide autogel in treating patients with NETs, through a comprehensive review of clinical trials, post-marketing surveillance, real-world evidence, and its safety profile. Specific adverse events, side effects, and potential risks associated with lanreotide autogel are discussed, along with risk mitigation strategies and recommendations for patient monitoring. EXPERT OPINION: The findings highlight the overall safety of lanreotide autogel in managing NETs, focusing on its efficacy in controlling hormone secretion, tumor progression, and symptom management. New safety concerns and precautions are also addressed to help healthcare providers make informed decisions when prescribing lanreotide autogel.

Cardiovascular Complications With Delivery Hospitalizations in Patients With Pulmonary Hypertension: A Nationwide Study From 2011 to 2020.

BACKGROUND: Pregnancy in patients with pulmonary hypertension (PH) is associated with a heightened risk of medical complications including right heart failure, pulmonary edema, and arrhythmias. Our study investigated the association between PH and these complications during delivery. METHODS AND RESULTS: The National Inpatient Sample was used to identify delivery hospitalizations from 2011 to 2020. Multivariable logistic regression was performed to study the association of PH with the primary outcomes of in-hospital medical and obstetric complications. A total of 37 482 207 delivery hospitalizations in women ≥18 years of age were identified, of which 9593 patients had PH. Pregnant patients with PH had higher incidence of complications during delivery including preeclampsia/eclampsia, arrhythmias, and pulmonary edema among others, compared with those without PH. Pregnant patients with PH also had a higher incidence of in-hospital mortality compared with those without PH (0.51% versus 0.007%). In propensity-matched analyses, PH was still significantly associated with a higher risk of in-hospital mortality (odds ratio [OR], 5.02 [95% CI, 1.82-13.90]; P=0.001), pulmonary edema (OR, 9.11 [95% CI, 6.34-13.10]; P<0.001), peripartum cardiomyopathy (OR, 1.85 [95% CI, 1.37-2.50]; P<0.001), venous thromboembolism (OR, 12.60 [95% CI, 6.04-26.10]; P<0.001), cardiac arrhythmias (OR, 6.11 [95% CI, 4.97-7.53]; P<0.001), acute kidney injury (OR, 3.72 [95% CI, 2.86-4.84]; P<0.001), preeclampsia/eclampsia (OR, 2.24 [95% CI, 1.95-2.58]; P<0.001), and acute coronary syndrome (OR, 2.01 [95% CI, 1.06-3.80]; P=0.03), compared with pregnant patients without PH. CONCLUSIONS: Delivery hospitalizations in patients with PH are associated with a high risk of mortality, pulmonary edema, peripartum cardiomyopathy, venous thromboembolism, arrhythmias, acute kidney injury, preeclampsia/eclampsia, and acute coronary syndrome.

Quasi-integrability and nonlinear resonances in cold atoms under modulation.

Quantum dynamics of a collection of atoms subjected to phase modulation has been carefully revisited. We present an exact analysis of the evolution of a two-level system (represented by a spinor) under the action of a time-dependent matrix Hamiltonian. The dynamics is shown to evolve on two coupled potential energy surfaces (PESs): one of them is binding, while the other one is scattering type. The dynamics is shown to be quasi-integrable with nonlinear resonances. The bounded dynamics with intermittent scattering at random moments presents a scenario reminiscent of Anderson and dynamical localization. We believe that a careful analytical investigation of a multi-component system that is classically non-integrable is relevant to many other fields, including quantum computation with multi-qubit systems.

Acetazolamide and Hydrochlorothiazide in Patients With Acute Decompensated Heart Failure: Insights From Recent Trials.

Acetazolamide and thiazide diuretics have been combined with loop diuretics to overcome diuretic resistance in heart failure patients. However, recent studies have assessed the upfront combination of acetazolamide and hydrochlorothiazide with loop diuretics in hospitalized patients with acute decompensated heart failure without loop diuretic resistance. We reviewed two recent randomized controlled trials on the upfront use of acetazolamide and thiazide diuretics in acute decompensated heart failure, respectively. When the two trials on acetazolamide are considered together, adding oral or intravenous acetazolamide to loop diuretics in decompensated heart failure patients resulted in increased diuresis and natriuresis. However, the effects were significantly higher in patients with serum bicarbonate ≥ 27 mmol/L and those with higher baseline glomerular filtration rate (GFR). Similarly, when the two trials on thiazide diuretics are considered together, adding hydrochlorothiazide to loop diuretics in decompensated heart failure patients resulted in increased diuresis and weight loss. However, it increases the risk of impaired renal function. When all the trials are considered together, the upfront use of acetazolamide may be helpful in carefully selected patients, including patients with underlying elevated bicarbonate levels (≥ 27 mmol/L) and those with good renal function (GFR > 50). Conversely, though the upfront use of thiazide diuretic added to intravenous furosemide improved diuretic response in acute decompensated heart failure, it causes an increased risk of worsening renal function and lack of clear evidence of reducing hospital length of stay.