Prior Use of Angiotensin-converting Enzyme Inhibitors or Angiotensin II Receptor Blockers and Clinical Outcomes of Sepsis and Septic Shock: A Systematic Review and Meta-analysis.

ABSTRACT: Sepsis and septic shock are life-threatening conditions that are associated with high mortality and considerable health care costs. The association between prior angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) use and outcomes after sepsis is elusive. The aim of this study was to evaluate the role of the prior use of ACEi or ARBs and outcomes after sepsis and septic shock. A relevant literature review was performed in 4 databases from inception until July 2022. Independent reviewers first screened the title, abstract, and full text, and then, data extraction and analysis were performed. One post hoc analysis of a trial and 6 retrospective cohort studies were included in this review. There were 22% lower odds of in-hospital/30-day mortality among patients who have used ACEi/ARBs in the past [23.83% vs. 37.20%; odds ratio (OR), 0.78, 95% confidence interval (CI), 0.64-0.96], and reduced 90-day mortality (OR, 0.80, 95% CI, 0.69-0.92). ACEi/ARBs users were found to have 31% lesser odds of developing acute kidney injury as compared with nonusers (OR, 0.69, 95% CI, 0.63-0.76). There was no significant difference in the length of hospital stay (MD 1.26, 95% CI, ‒7.89 to 10.42), need for renal replacement therapy (OR, 0.71, 95% CI, 0.13-3.92), mechanical ventilation (OR, 1.10, 95% CI, 0.88-1.37) or use of vasopressors (OR, 1.21, 95% CI, 0.91-1.61). Based on this analysis, prior use of ACEi/ARBs lowers the risk of mortality and adverse renal events in patients with sepsis and septic shock.

Bubble devices versus other pressure sources for nasal continuous positive airway pressure in preterm infants.

BACKGROUND: Several types of pressure sources, including underwater bubble devices, mechanical ventilators, and the Infant Flow Driver, are used for providing continuous positive airway pressure (CPAP) to preterm infants with respiratory distress. It is unclear whether the use of bubble CPAP versus other pressure sources is associated with lower rates of CPAP treatment failure, or mortality and other morbidity.  OBJECTIVES: To assess the benefits and harms of bubble CPAP versus other pressure sources (mechanical ventilators or Infant Flow Driver) for reducing treatment failure and associated morbidity and mortality in newborn preterm infants with or at risk of respiratory distress. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2023, Issue 1); MEDLINE (1946 to 6 January 2023), Embase (1974 to 6 January 2023), Maternity & Infant Care Database (1971 to 6 January 2023), and the Cumulative Index to Nursing and Allied Health Literature (1982 to 6 January 2023). We searched clinical trials databases and the reference lists of retrieved articles. SELECTION CRITERIA: We included randomised controlled trials comparing bubble CPAP with other pressure sources (mechanical ventilators or Infant Flow Driver) for the delivery of nasal CPAP to preterm infants. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Two review authors separately evaluated trial quality, extracted data, and synthesised effect estimates using risk ratio (RR), risk difference (RD), and mean difference. We used the GRADE approach to assess the certainty of the evidence for effects on treatment failure, all-cause mortality, neurodevelopmental impairment, pneumothorax, moderate-severe nasal trauma, and bronchopulmonary dysplasia. MAIN RESULTS: We included 15 trials involving a total of 1437 infants. All trials were small (median number of participants 88). The methods used to generate the randomisation sequence and ensure allocation concealment were unclear in about half of the trial reports. Lack of measures to blind caregivers or investigators was a potential source of bias in all of the included trials. The trials took place during the past 25 years in care facilities internationally, predominantly in India (five trials) and Iran (four trials). The studied pressure sources were commercially available bubble CPAP devices versus a variety of mechanical ventilator (11 trials) or Infant Flow Driver (4 trials) devices.  Meta-analyses suggest that the use of bubble CPAP compared with mechanical ventilator or Infant Flow Driver CPAP may reduce the rate of treatment failure (RR 0.76, 95% confidence interval (CI) 0.60 to 0.95; (I² = 31%); RD -0.05, 95% CI -0.10 to -0.01; number needed to treat for an additional beneficial outcome 20, 95% CI 10 to 100; 13 trials, 1230 infants; low certainty evidence). The type of pressure source may not affect mortality prior to hospital discharge (RR 0.93, 95% CI 0.64 to 1.36 (I² = 0%); RD -0.01, 95% CI -0.04 to 0.02; 10 trials, 1189 infants; low certainty evidence). No data were available on neurodevelopmental impairment. Meta-analysis suggests that the pressure source may not affect the risk of pneumothorax (RR 0.73, 95% CI 0.40 to 1.34 (I² = 0%); RD -0.01, 95% CI -0.03 to 0.01; 14 trials, 1340 infants; low certainty evidence). Bubble CPAP likely increases the risk of moderate-severe nasal injury (RR 2.29, 95% CI 1.37 to 3.82 (I² = 17%); RD 0.07, 95% CI 0.03 to 0.11; number needed to treat for an additional harmful outcome 14, 95% CI 9 to 33; 8 trials, 753 infants; moderate certainty evidence). The pressure source may not affect the risk of bronchopulmonary dysplasia (RR 0.76, 95% CI 0.53 to 1.10 (I² = 0%); RD -0.04, 95% CI -0.09 to 0.01; 7 trials, 603 infants; low certainty evidence).  AUTHORS' CONCLUSIONS: Given the low level of certainty about the effects of bubble CPAP versus other pressure sources on the risk of treatment failure and most associated morbidity and mortality for preterm infants, further large, high-quality trials are needed to provide evidence of sufficient validity and applicability to inform context- and setting-relevant policy and practice.

Masks versus prongs as interfaces for nasal continuous positive airway pressure in preterm infants.

BACKGROUND: Nasal masks and nasal prongs are used as interfaces for providing continuous positive airway pressure (CPAP) for preterm infants with or at risk of respiratory distress, either as primary support after birth or as ongoing support after endotracheal extubation from mechanical ventilation. It is unclear which type of interface is associated with lower rates of CPAP treatment failure, nasal trauma, or mortality and other morbidity. OBJECTIVES: To assess the benefits and harms of nasal masks versus nasal prongs for reducing CPAP treatment failure, nasal trauma, or mortality and other morbidity in newborn preterm infants with or at risk of respiratory distress. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was October 2021. SELECTION CRITERIA: We included randomised controlled trials comparing masks versus prongs as interfaces for delivery of nasal CPAP in newborn preterm infants (less than 37 weeks' gestation) with or at risk of respiratory distress. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. treatment failure, 2. all-cause mortality, and 3. neurodevelopmental impairment. Our secondary outcomes were 4. pneumothorax, 5. moderate-severe nasal trauma, 6. bronchopulmonary dysplasia, 7. duration of CPAP use, 8. duration of oxygen supplementation, 9. duration of hospitalisation, 10. patent ductus arteriosus receiving medical or surgical treatment, 11. necrotising enterocolitis, 12. severe intraventricular haemorrhage, and 13. severe retinopathy of prematurity. We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: We included 12 trials with 1604 infants. All trials were small (median number of participants 118). The trials occurred after 2001 in care facilities internationally, predominantly in India (eight trials). Most participants were preterm infants of 26 to 34 weeks' gestation who received nasal CPAP as the primary form of respiratory support after birth. The studied interfaces included commonly used commercially available masks and prongs. Lack of measures to blind caregivers or investigators was a potential source of performance and detection bias in all the trials. Meta-analyses suggested that use of masks compared with prongs may reduce CPAP treatment failure (risk ratio (RR) 0.72, 95% confidence interval (CI) 0.58 to 0.90; 8 trials, 919 infants; low certainty). The type of interface may not affect mortality prior to hospital discharge (RR 0.83, 95% CI 0.56 to 1.22; 7 trials, 814 infants; low certainty). There are no data on neurodevelopmental impairment. Meta-analyses suggest that the choice of interface may result in little or no difference in the risk of pneumothorax (RR 0.93, 95% CI 0.45 to 1.93; 5 trials, 625 infants; low certainty). Use of masks rather than prongs may reduce the risk of moderate-severe nasal injury (RR 0.55, 95% CI 0.44 to 0.71; 10 trials, 1058 infants; low certainty). The evidence is very uncertain about the effect on bronchopulmonary dysplasia (RR 0.69, 95% CI 0.46 to 1.03; 7 trials, 843 infants; very low certainty). AUTHORS' CONCLUSIONS: The available trial data provide low-certainty evidence that use of masks compared with prongs as the nasal CPAP interface may reduce treatment failure and nasal injury, and may have little or no effect on mortality or the risk of pneumothorax in newborn preterm infants with or at risk of respiratory distress. The effect on bronchopulmonary dysplasia is very uncertain. Large, high-quality trials would be needed to provide evidence of sufficient validity and applicability to inform policy and practice.

Anti-Obesity Potential of Ponciri Fructus: Effects of Extracts, Fractions and Compounds on Adipogenesis in 3T3-L1 Preadipocytes.

BACKGROUND: Ponciri Fructus, a crude drug consisting of the dried immature fruits of Poncirus trifoliata (L.) Raf., is a popular folk medicine used for the treatment of allergy and gastrointestinal disorders in Korea and China. In this study, the anti-adipogenic activity of extracts and isolated compounds were evaluated using 3T3-L1 preadipocytes. METHODS: Dried immature fruits were extracted and fractionated into n-hexane, ethyl acetate (EtOAc), n-butanol and water-soluble fractions. The ethanol extract and fractions were tested for anti-adipogenic activity in the 3T3-L1 cell line. The active fractions (n-hexane and EtOAc fractions) were further subjected to chromatographic techniques to isolate and identify active compounds. Furthermore, the isolated compounds were evaluated for their anti-adipogenic activity. RESULTS: Altogether, seven compounds, including two flavonoids, one phytosteroid and four coumarin derivatives, were isolated. Ethanol extract, n-hexane fraction, EtOAc fraction and three isolated compounds (phellopterin, oxypeucedanin and poncirin) showed significant anti-adipogenic activity as observed by reduced lipid deposition in differentiated 3T3-L1 cells. Further, oxypeucedanin downregulated the key adipogenic markers, such as peroxisome proliferator-activated receptors proteins γ (PPAR-γ), sterol response element binding proteins-1 (SREBP-1), CCAAT/enhancer binding proteins-α (C/EBP-α), adipocyte-specific lipid binding proteins (FABP-4), adipocyte fatty acid binding proteins (aP2), lipoprotein lipase (LPL) and leptin. CONCLUSION: This study indicated that the ethanol extract, hexane fraction and ethyl acetate fraction of P. trifoliata fruits possess strong anti-adipogenic activity, containing the active compounds such as phellopterin, oxypeucedanin and poncirin. Further research is recommended to explore their efficacy and safety in animal and clinical models.

Contemporary Diagnosis and Management of Rheumatic Heart Disease: Implications for Closing the Gap: A Scientific Statement From the American Heart Association.

The global burden of rheumatic heart disease continues to be significant although it is largely limited to poor and marginalized populations. In most endemic regions, affected patients present with heart failure. This statement will seek to examine the current state-of-the-art recommendations and to identify gaps in diagnosis and treatment globally that can inform strategies for reducing disease burden. Echocardiography screening based on World Heart Federation echocardiographic criteria holds promise to identify patients earlier, when prophylaxis is more likely to be effective; however, several important questions need to be answered before this can translate into public policy. Population-based registries effectively enable optimal care and secondary penicillin prophylaxis within available resources. Benzathine penicillin injections remain the cornerstone of secondary prevention. Challenges with penicillin procurement and concern with adverse reactions in patients with advanced disease remain important issues. Heart failure management, prevention, early diagnosis and treatment of endocarditis, oral anticoagulation for atrial fibrillation, and prosthetic valves are vital therapeutic adjuncts. Management of health of women with unoperated and operated rheumatic heart disease before, during, and after pregnancy is a significant challenge that requires a multidisciplinary team effort. Patients with isolated mitral stenosis often benefit from percutaneous balloon mitral valvuloplasty. Timely heart valve surgery can mitigate the progression to heart failure, disability, and death. Valve repair is preferable over replacement for rheumatic mitral regurgitation but is not available to the vast majority of patients in endemic regions. This body of work forms a foundation on which a companion document on advocacy for rheumatic heart disease has been developed. Ultimately, the combination of expanded treatment options, research, and advocacy built on existing knowledge and science provides the best opportunity to address the burden of rheumatic heart disease.

Anti-Adipogenic and Anti-Inflammatory Activities of (-)-epi-Osmundalactone and Angiopteroside from Angiopteris helferiana C.Presl.

Angiopteris helferiana C.Presl is a gigantic fleshy-type fern, belonging to Marattiaceae family. In previous study, we reported the potent anti-adipogenic and anti-inflammatory activities of ethylacetate (EtOAc) and n-butanol (BuOH) fractions of methanol extract of rhizomes of A. helferiana. In continuation, in this study, we report the isolation, characterization, and bioactivity analysis of principle bioactive compounds in these fractions. (-)-epi-Osmundalactone (1) and angiopteroside (2) were isolated from EtOAc and BuOH fractions, respectively. The structures of these compounds were established on the basis of NMR spectroscopic data. The quantification study using UPLC revealed the contents of compounds 1 and 2 in the dried rhizome to be 1.54% and 3.2%, respectively. These compounds were evaluated for their anti-adipogenic and anti-inflammatory activities using 3T3-L1 and RAW 264.7 cells, respectively. Compound 1 (2.5 µg/mL) and 2 (20 µg/mL) inhibited the lipid production by 35% and 25%, respectively. Regarding the anti-inflammatory activity, compound 1 (5 µg/mL) inhibited the nitrite production by nearly 82%. In conclusion, the presence of potent anti-adipogenic and anti-inflammatory compounds in A. helferiana indicate its potential role in the use of herb-based treatment for obesity and other related diseases.

Bioassay-guided isolation of active anti-adipogenic compound from royal jelly and the study of possible mechanisms.

BACKGROUND: Royal jelly (RJ) has been used traditionally for dietary, cosmetic and health purposes for a long time in different parts of the world. Scientific studies have also shown its numerous health-promoting properties including hypoglycemic and anti-hypercholesterolemic action. In this study, we investigated the anti-adipogenic activity of RJ in 3 T3-L1 cells and isolated the major responsible root component for the activity. METHODS: An active anti-adipogenic compound was isolated through bioassay-guided isolation process by successive treatment of RJ and its active fractions on 3 T3-L1 cell line. (E)-10-Hydroxy-2-decenoic Acid (10-HDA) was identified using NMR spectroscopy and ultra-performance liquid chromatography (UPLC). As 10-HDA showed significant anti-adipogenic activity with Oil Red O staining and TG content assay on 3 T3-L1 adipocytes, further study was carried out in molecular level for the expression of adipogenic transcription factors such as PPARγ, FABP4, C/EBPα, SREBP-1c, and Leptin. The effect of 10-HDA on preliminary molecules such as pAkt, pERK, C/EBPß, and pCREB were studied in the early stage of adipogenesis. The effect of 10-HDA on reactive oxygen species (ROS) production in fully differentiating adipocytes was measured by nitro blue tetrazolium (NBT) assay. RESULT: Results showed that triacylglycerol accumulation and ROS production was markedly suppressed by 10-HDA. Preliminary molecules such as pAkt, pERK, pCERB, and C/EBPß were found to be down-regulated by 10-HDA, which led to down-regulation of key adipogenic transcription factors such as PPARγ, FABP4, CEBPα, SREBP-1c, and Leptin on 3 T3-L1 adipocytes. CONCLUSION: Our results suggest that anti-adipogenesis of 10-HDA on 3 T3-L1 adipocyte takes place via two mechanisms: inhibition of cAMP/PKA pathway and inhibition of p-Akt and MAPK dependent insulin signaling pathway. So it is considered that 10-HDA, a major component of RJ, can be a potential therapeutic medicine for obesity.

Exploration of Underlying Mechanism of Anti-adipogenic Activity of Sulfuretin.

Sulfuretin is a natural flavonoid found in the plant Rhus verniciflua STOKES. The plant has been traditionally used as medicinal agent for antiviral, cathartic, diaphoretic, anti-rheumatic and sedative activities in East Asia. In this study we isolated and identified sulfuretin from R. verniciflua and investigated its anti-adipogenic activity against 3T3-L1 preadipocytes cells. We evaluated the effects of sulfuretin on the adipogenic transcription factors like peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), fatty acid synthase (FAS), Fabp4, adiponectin and zinc fingerprint protein (Zfp) 521 by gene expression (real-time QPCR) and Western blot analysis. Sulfuretin treatment at Day 0 and 2 showed significant reduction of lipid production in 3T3-L1 cells in concentration dependent manner. Gene expression analysis (real-time PCR) revealed that sulfuretin inhibited the both major adipogenic factors (C/EBPα, C/EBPß and PPARγ) and minor adipogenic factors (sterol regulatory element-binding protein (SREBP1c), adiponectin, FAS, Fabp4, Zfp423, and Ebf1). Western blot analysis showed the increased expression of ß-catenin and suppression of PPARγ after sulfuretin treatment. Overall, sulfuretin is a natural flavonoid having potent anti-adipogenic activity through the suppression of major adipogenic factors C/EBPα, C/EBPß and PPARγ, which initiate adipogenesis.

Sodium butyrate has context-dependent actions on dipeptidyl peptidase-4 and other metabolic parameters.

Sodium butyrate (SB) has various metabolic actions. However, its effect on dipeptidyl peptidase 4 (DPP-4) needs to be studied further. We aimed to evaluate the metabolic actions of SB, considering its physiologically relevant concentration. We evaluated the effect of SB on regulation of DPP-4 and its other metabolic actions, both in vitro (HepG2 cells and mouse mesangial cells) and in vivo (high fat diet [HFD]-induced obese mice). Ten-week HFD-induced obese C57BL/6J mice were subjected to SB treatment by adding SB to HFD which was maintained for an additional 16 weeks. In HepG2 cells, SB suppressed DPP-4 activity and expression at sub-molar concentrations, whereas it increased DPP-4 activity at a concentration of 1,000 µM. In HFD-induced obese mice, SB decreased blood glucose, serum levels of insulin and IL-1ß, and DPP-4 activity, and suppressed the increase in body weight. On the contrary, various tissues including liver, kidney, and peripheral blood cells showed variable responses of DPP-4 to SB. Especially in the kidney, although DPP-4 activity was decreased by SB in HFD-induced obese mice, it caused an increase in mRNA expression of TNF-α, IL-6, and IL-1ß. The pro-inflammatory actions of SB in the kidney of HFD-induced obese mice were recapitulated by cultured mesangial cell experiments, in which SB stimulated the secretion of several cytokines from cells. Our results showed that SB has differential actions according to its treatment dose and the type of cells and tissues. Thus, further studies are required to evaluate its therapeutic relevance in metabolic diseases including diabetes and obesity.

Health professionals' experience on District Health Information System (DHIS2) and its utilization at local levels in Gandaki province, Nepal: A qualitative study.

DHIS2 is a web-based platform primarily used in developing countries, ensuring reliable data and aiding decentralized decision-making. The Ministry of Health and Population has greatly emphasized using DHIS2 for data entry and reporting. However, studies regarding health workers' experiences on DHIS2 and the utilization of data at the local level remain limited. Therefore, this study aims to investigate the usage and practical experience of DHIS2 at the local levels of Gandaki province, Nepal. An exploratory qualitative study was conducted in the Gandaki province from February to August 2023. We conducted twenty in-depth interviews among the DHIS2 users at local levels, health posts, and provincial health directorate using in-depth interview guidelines. The study participants were selected purposively. Thematic analysis was conducted to analyze the data, and NVivo was used to facilitate data analysis. Health professionals demonstrated dedication and commitment to use DHIS2 for reporting. DHIS2 has facilitated timely reporting, data storage, data analysis and visualization, feedback and communication mechanisms, and service delivery. Users' self-motivation and support from the local and provincial levels and regular review and program-specific review meetings were major facilitators for DHIS2 use. Similarly, technical issues, poor internet connectivity, power outages, and inexperienced health professionals were the significant challenges to using DHIS2. The basic and refresher training needed improvement at all levels, and learning materials were unavailable in health facilities. In addition, the data utilization at the local level in various actions was unsatisfactory despite sufficient data. Health professionals have been facilitated by DHIS2 in various actions. Capacity building of health professionals on data analysis and interpretations, continued onsite coaching, reliable internet connectivity, availability of learning materials, and improved server capacity are needed to enhance the performance of DHIS2 at the local level.

How Is It Possible to Treat Diseases Without Medicine?: A Qualitative Study on the Attitude and Perceived Benefits of Yoga and Naturopathy Among Patients Admitted at an Inpatient Hospital.

Background: Yoga and naturopathy (Y&N) is a system of medicine primarily focusing on restoration of health and well-being. Objective of this study is to understand the knowledge, attitude, and perception about Y&N among the inpatients of a government Y&N institution in south India. Methods: Focus group discussion was conducted in eight adult patients aged between 30 and 60 years who took Y&N treatments for a period of 10 days or more. Purposive sampling method was adopted. Oral informed consent was obtained. Results: Knowledge about the Y&N system of medicine was primarily through referral or "word of mouth." Perceived benefits were both physical and psychological. Uniqueness of the hospital as mentioned by participants includes individual attention, tailor-made treatment protocols, and one-to-one care to the needy patients. Conclusion: An integrated approach is very much essential that might bring about better treatment outcomes in patients.

Immediate vs. multistage revascularization of non-infarct coronary artery(-ies) in patients with hemodynamically stable multivessel disease acute myocardial infarction: a systematic review and meta-analysis.

BACKGROUND: Untreated multivessel disease (MVD) in acute myocardial infarction (AMI) has been linked to a higher risk of recurrent ischemia and death within one year . Current guidelines recommend percutaneous coronary intervention (PCI) for significant non-infarct artery (-ies) (non-IRA) stenosis in hemodynamically stable AMI patients with MVD, either during or after successful primary PCI, within 45-days. However, deciding the timing of revascularization for non-IRA in cases of MVD is uncertain. METHODS: This meta-analysis was performed based on PRISMA guidelines after registering in PROSPERO (CRD42023472652). Databases were searched for relevant articles published before 10 November 2023. Pertinent data from the included studies were extracted and analyzed using RevMan v5.4. RESULTS: Out of 640 studies evaluated, there were 13 RCTs with 5144 patients with AMI with MVD. The immediate non-IRA PCI is associated with a significantly lower occurrence of unplanned ischemia-driven PCI (OR 0.60; confidence interval [CI] 0.44-0.83) and target-vessel revascularization (OR 0.72; CI 0.53-0.97) . Although there is a favorable trend for major adverse cardiovascular and cerebrovascular events (MACCE), nonfatal AMI, cerebrovascular events, and major bleeding in the immediate non-culprit artery (-ies) PCI, those were statistically non-significant. Similarly, all-cause mortality, cardiovascular mortality, stent thrombosis, and acute renal insufficiency did not show significant differences between two groups. CONCLUSION: Among hemodynamically stable patients with multivessel AMI, the immediate PCI strategy was superior to the multistage PCI strategy for the unplanned ischemia-driven PCI and target-vessel revascularization while odds are favorable in terms of MACCE, nonfatal AMI, cerebrovascular events, and major bleeding at longest follow-up.

Safety and efficacy of direct oral anticoagulants in comparison to warfarin in obese patients with atrial fibrillation: A systematic review and meta-analysis.

Background and Aim: Obesity affects nearly 650 million adults worldwide, and the prevalence is steadily rising. This condition has significant adverse effects on cardiovascular health, increasing the risk of hypertension, coronary artery disease, heart failure, and atrial fibrillation (AF). While anticoagulation for obese patients with AF is a well-established therapy for the prevention of thromboembolism, the safety and efficacy of different anticoagulants in this specific population are not well explored. This meta-analysis aimed to compare direct oral anticoagulants (DOAC) to vitamin K antagonists in obese populations with AF. Methods: The PRISMA guidelines were followed for this meta-analysis, registered in PROSPERO (CRD42023392711). PubMed, PubMed Central, Embase, Cochrane Library, and Scopus databases were searched for relevant articles from inception through January 2023. Two independent authors screened titles and abstracts, followed by a full-text review in Covidence. Data were extracted in Microsoft Excel and analyzed using RevMan v5.4 using odds ratio as an effect measure. Results: Two thousand two hundred fifty-nine studies were identified from the database search, and 18 were included in the analysis. There were statistically significant reductions in the odds of ischemic and hemorrhagic stroke in the DOAC group compared with the VKA group (OR 0.70, CI 0.66-0.75) and (OR 0.47, CI 0.35-0.62), respectively. In addition, the DOAC group exhibited lower odds of systemic embolism (OR 0.67, CI 0.54-0.83), major bleeding (OR 0.62, CI 0.54-0.72), and composite outcome (OR 0.72, CI 0.63-0.81). Conclusion: Based on the findings from this meta-analysis, DOACs demonstrate superior safety and efficacy in obese patients with AF compared with VKAs. These results may have significant implications for guiding anticoagulation strategies in this patient population.

Differences in clinical presentation and outcomes in pregnancy-associated Takotsubo Syndrome- A scoping review of the literature: Outcomes in pregnancy-associated Takotsubo.

BACKGROUND: Takotsubo syndrome (TS) during pregnancy and postpartum is rare but may lead to significant maternal and fetal morbidity. We compared clinical characteristics and prognosis according to [a] timing of presentation (pregnancy vs post-partum) and [b] modes of delivery (cesarean section vs vaginal delivery). METHODS: Systematic review of articles published in PubMed, Scopus, Embase, and Medline databases from inception to July 30, 2023. Patient demographics, obstetric, electrocardiographic, laboratory, echocardiographic characteristics, and prognosis were summarized descriptively. RESULTS: An initial database search identified 2162 articles, of which 81 studies were included in this review. TS during pregnancy can have emotional, obstetric, and metabolic triggers and has a higher proportion of adverse fetal outcomes when compared with women who developed TS postpartum. Women with TS after cesarean section had an earlier onset and higher proportion of anesthesia use when compared with those who developed TS after vaginal delivery. There were no differences regarding the degree of systolic dysfunction or the need for advanced therapies, including ventilator support, intra-aortic balloon pump, and extracorporeal membrane oxygenation among groups. CONCLUSIONS: TS is associated with various triggers and adverse fetal outcomes when it develops during pregnancy than in the postpartum period. TS occurs more rapidly and with a more aggressive course after cesarean section than after vaginal delivery.

Evaluation of Anti-Obesity and Antidiabetic Activities of Orostachys japonicus in Cell and Animal Models.

Orostachys japonicus is a popular traditional medicinal herb used in Asian countries. This study is focused on evaluating its role in lipid and glucose metabolism in cell and animal models to establish the plant as an anti-obesity and antidiabetic herb. A butanol fraction of O. japonicus was used in the study. The lipid production was evaluated by the Oil Red O technique while the expression of adipogenic markers by Western blotting and RT-PCR using 3T3-L1 preadipocyte. The effect on glucose uptake activity was evaluated in C2C12 myoblast cells. The animal study was carried out in C57BL mice to evaluate anti-obesity activity using the high-fat diet model. The evaluation of serum lipid, blood glucose, adipogenic and fibrosis markers in the liver, and fat deposition in the liver and adipose tissue (by histology) of mice was conducted. Butanol fraction of O. japonicus significantly inhibited the lipid production in the 3T3-L1 cells and reduced the expression of PPARγ, C/EBPα, SREBP-1c and aP2. It enhanced glucose uptake in insulin-resistant C2C12 myoblast cells. It reduced body weight, triglycerides, and blood glucose in the obese mice. It significantly inhibited lipid accumulation in the liver and adipose tissue of obese mice along with suppression of expression of adipogenic and fibrosis markers in the liver. In summary, supporting the previous results, this study helped to establish the potent anti-obesity, antidiabetic, and liver-protecting effect of the butanol fraction of O. japonicus.

Transcarotid versus trans-axillary/subclavian transcatheter aortic valve replacement (TAVR): A systematic review and meta-analysis.

BACKGROUND: Transcatheter Aortic Valve Replacement (TAVR) is the treatment of choice in patients with severe aortic stenosis. Transcarotid (TCa) or Trans-axillary/subclavian (TAx/Sc) are safer and less invasive non-femoral approaches, where transfemoral access is difficult or impossible to obtain. METHODS: This meta-analysis was performed based on PRISMA guidelines after registering in PROSPERO (CRD42023482842). This meta-analysis was performed to compare the safety of the transcarotid and trans-axillary/subclavian approach for TAVR including studies from inception to October 2023. RESULTS: Seven studies with a total of 6227 patients were included in the analysis (TCa: 2566; TAx/Sc: 3661). Transcarotid TAVR approach had a favorable trend for composite of stroke and all-cause mortality (OR 0.79, CI 0.60-1.04), all-cause mortality, stroke, major vascular complication, and new requirement of permanent pacemaker though those were statistically insignificant. On sub-analysis of the results of the studies based on the territory (USA vs French), composite outcome of all cause mortality, stroke and major bleeding (OR 0.54, CI 0.54-0.81), composite of stroke and all cause mortality (OR 0.64, CI 0.50-0.81), and stroke/TIA (OR 0.53, CI 0.39-0.73) showed lower odds of occurrence among patient managed with TCa approach in the American cohort. CONCLUSION: Overall, transcarotid approach had favorable though statistically insignificant odds for composite (stroke and all-cause mortality) and individual outcomes (stroke, all-cause mortality, etc.). There are significant variations in observed outcomes based on study's geographic location. Large prospective randomized clinical trials comparing the two approaches with representative samples are necessary to guide the clinicians in choosing among these approaches.

Paradoxical Vocal Fold Dysfunction Mimicking Bronchial Asthma in a Young Female Patient.

Inducible laryngeal obstruction (ILO)/paradoxical vocal fold motion (PVFM) is a reversible narrowing of the larynx that results from vocal fold motion dysfunction. Distinguishing ILO from asthma can be challenging, as they can coexist, and standard tests may not be able to differentiate between the two. However, a flexible laryngoscopy can promptly diagnose ILO. Unfortunately, ILO is often overlooked as a potential cause when evaluating patients with sudden-onset breathing difficulties and respiratory distress. We present a case of a young female who sought frequent treatment at the emergency room (ER) with symptoms of shortness of breath (SOB), rapid heart rate, rapid breathing, and anxiety. Despite receiving treatment for acute asthma attacks, her symptoms persisted. During her most recent hospital admission, a flexible laryngoscopy revealed abnormal vocal fold movements, indicating paradoxical vocal fold dysfunction (PVFD) and muscle tension dysphonia (MTD). A comprehensive treatment approach involving speech therapy, pulmonology, and psychiatry led to significant clinical improvement. This case report highlights the importance of raising awareness among healthcare providers about ILO potentially mimicking bronchial asthma exacerbation.

Analysis of Dengue Transmission Dynamic Model by Stability and Hopf Bifurcation with Two-Time Delays.

BACKGROUND: Mathematical models reflecting the epidemiological dynamics of dengue infection have been discovered dating back to 1970. The four serotypes (DENV-1 to DENV-4) that cause dengue fever are antigenically related but different viruses that are transmitted by mosquitoes. It is a significant global public health issue since 2.5 billion individuals are at risk of contracting the virus. METHODS: The purpose of this study is to carefully examine the transmission of dengue with a time delay. A dengue transmission dynamic model with two delays, the standard incidence, loss of immunity, recovery from infectiousness, and partial protection of the human population was developed. RESULTS: Both endemic equilibrium and illness-free equilibrium were examined in terms of the stability theory of delay differential equations. As long as the basic reproduction number (R0) is less than unity, the illness-free equilibrium is locally asymptotically stable; however, when R0 exceeds unity, the equilibrium becomes unstable. The existence of Hopf bifurcation with delay as a bifurcation parameter and the conditions for endemic equilibrium stability were examined. To validate the theoretical results, numerical simulations were done. CONCLUSIONS: The length of the time delay in the dengue transmission epidemic model has no effect on the stability of the illness-free equilibrium. Regardless, Hopf bifurcation may occur depending on how much the delay impacts the stability of the underlying equilibrium. This mathematical modelling is effective for providing qualitative evaluations for the recovery of a huge population of afflicted community members with a time delay.

Utility of neutrophil-to-high-density lipoprotein-cholesterol ratio in patients with coronary artery disease: a narrative review.

The neutrophil-to-high-density lipoprotein-cholesterol ratio (NHR) is thought to reflect inflammatory status and dyslipidaemia, both of which play significant roles in coronary artery disease (CAD). The objective of this narrative review is to summarise the results of studies that have explored the utility of NHR for the diagnosis and management of CAD. The PubMed, Google Scholar, Scopus, Embase and Web of Science databases were searched for articles related to NHR from their inception to October 2022. Seven relevant articles were obtained for review. There were unclear relationships of NHR with age, sex, smoking status, hypertension and diabetes. However, NHR had a sensitivity and specificity as high as 94.8% and 59%, respectively, for the identification of significant coronary stenosis. NHR was also a superior predictor of prognosis to conventional parameters. NHR had a sensitivity and specificity as high as 77.6% and 74.2%, respectively, for the prediction of adverse events, including mortality, associated with acute coronary syndrome. Thus, NHR could be used in clinical cardiovascular medicine for risk stratification and the prediction of the short-term and long-term outcomes of CAD. However, more studies are required before a quantitative assessment of the efficacy of NHR for use in patient management can be completed.