Catheter ablation versus medical therapy in atrial fibrillation: an umbrella review of meta-analyses of randomized clinical trials.

This umbrella review synthesizes data from 17 meta-analyses investigating the comparative outcomes of catheter ablation (CA) and medical treatment (MT) for atrial fibrillation (AF). Outcomes assessed were mortality, risk of hospitalization, AF recurrence, cardiovascular events, pulmonary vein stenosis, major bleeding, and changes in left ventricular ejection fraction (LVEF) and MLHFQ score. The findings indicate that CA significantly reduces overall mortality and cardiovascular hospitalization with high strength of evidence. The risk of AF recurrence was notably lower with CA, with moderate strength of evidence. Two associations reported an increased risk of pulmonary vein stenosis and major bleeding with CA, supported by high strength of evidence. Improved LVEF and a positive change in MLHFQ were also associated with CA. Among patients with AF and heart failure, CA appears superior to MT for reducing mortality, improving LVEF, and reducing cardiovascular rehospitalizations. In nonspecific populations, CA reduced mortality and improved LVEF but had higher complication rates. Our findings suggest that CA might offer significant benefits in managing AF, particularly in patients with heart failure. However, the risk of complications, including pulmonary vein stenosis and major bleeding, is notable. Further research in understudied populations may help refine these conclusions.

Variations of blood metabolites in single- and multiple-bearing Ossimi ewes during the transition period.

Evaluation of the metabolic profile indices allows early detection and treatment of various metabolic disorders during the transition period in ewes. This study aimed to determine the variations in the blood metabolites around lambing in Ossimi ewes. The blood metabolites were investigated in ewes with single (n = 27) and multiple (n = 9) lambs at 3- and 1-week pre-lambing and 3-week post-lambing. The plasma concentrations of glucose were higher in single-bearing ewes than those in multiple-bearing ewes (p < .05), moreover, its lowest value was measured at 1-week prepartum in both groups. Throughout the study period, the serum concentrations of non-esterified fatty acids (NEFA) were significantly increased in ewes with multiple lambs compared to ewes with single lambs (p < .05), and the highest value was found at 1-week before parturition in both groups. In addition, the serum level of beta-hydroxybutyric acid (BHBA) was higher at 3-week postpartum, and it was significantly increased in multiple-bearing ewes than that in single-bearing ones (p < .05) at 3-week pre-lambing. In both groups, the lowest values of total proteins were determined 1-week before lambing, and its concentrations, at 3- and 1-week prepartum, were higher in ewes with single lambs than those with multiple lambs (p < .05). In contrast, the serum concentrations of albumin were significantly lowered 1-week postpartum (p < .05), and without significant differences between both groups (p > .05). The serum activities of aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) were significantly increased at 1-week after parturition in both groups (p < .05). Furthermore, the serum activities of AST were higher in multiple-bearing ewes than those in single-bearing ones at 3-week pre-lambing and 3-week post-lambing (p < .05). Variable positive and negative correlations were determined among the blood metabolites. In conclusion, physiological adaptations are associated with the fluctuation of the blood metabolites around lambing. The higher the number of foetuses the higher the metabolic variations in Ossimi ewes. Therefore, regular metabolic profiling for health monitoring may be necessary to avoid disease development during the transition period.

Behavioral circadian phenotypes are associated with the risk of elevated body mass index.

BACKGROUND: Metabolic dysfunction and obesity rates are on the rise. Although the central modes of circadian disruption has been studied in relation to the risk of obesity, the role of eating time has remained unclear. Here, we aimed to assess circadian behavioral phenotypes and their association with the risk of elevated body mass index (BMI). METHODS: This was a prospective cross-sectional study of individuals presenting for colorectal cancer screening colonoscopy. Participants completed demographic questionnaires, The Munich ChronoType Questionnaire (MCTQ), and Food Timing Screener (FTS). The primary outcome of the study was the association between circadian phenotypes and elevated BMI. RESULTS: A total of 488 individuals completed the survey, with a mean (SD) age of 57.5 (10.8) years. The mean body mass index (BMI) was 28.8 (6.1) kg/m2, with 72.3% of individuals met criteria for elevated BMI. Four circadian behavioral phenotypes were generated: early chronotype with regular food timing (ER) (34.7%), early chronotype with irregular food timing (EI) (11.7%), intermediate/late chronotype with regular food timing (LR) (33.9%), and intermediate/late chronotype with irregular food timing (LI) (19.7%). In a multivariable regression analysis, LI phenotype had 2.9 times higher odds of elevated BMI as compared to ER phenotype (OR 2.9, 95% CI 1.3-6.7, P = 0.01). CONCLUSION: The combination of late chronotype and irregular food timing, representative of a behavioral circadian rhythm disruption, is associated with higher rates of elevated BMI. The majority of individuals with this abnormal circadian phenotype were younger than 60 years old. This observation is especially relevant because of the ongoing rise in the obesity rates among young adults. LEVEL III: Evidence obtained from well-designed cohort or case-control analytic studies.

Composite nanofibers membranes of poly(vinyl alcohol)/chitosan for selective lead(II) and cadmium(II) ions removal from wastewater.

The nanofibers membranes were fabricated by poly(vinyl alcohol)/chitosan (PVA/Chi) using an electro-spun technique for selective and high adsorption of lead (Pb(II)) and cadmium (Cd(II)) ions based on the solution acidity. The PVA/Chi NFs membranes were characterized systematically using several instrumentations. In addition, several experimental parameters such as initial metal ions concentration, interaction time, adsorbent dosage, solution pH and the effects of competing ions on Pb(II) and Cd(II) adsorption were evaluated. The adsorption data were also clarified that the PVA/Chi NFs membranes were exhibited high kinetic performances towards the both toxic ions at the optimum conditions. The adsorption data were manipulated using different kinetics models, and it was confirmed that only pseudo-second-order model obeyed the adsorption kinetics for Pb(II) and Cd(II) ions. Similarly, the equilibrium data were well fitted with the Langmuir adsorption isotherms model, and the maximum adsorption capacity was 266.12 and 148.79 mg/g for Pb(II) and Cd(II) ions, respectively. The Pb(II) and Cd(II) ions adsorptions were also measured to know the selectivity with simulated environmental solution, and the data were confirmed the high selectivity to Pb(II) and Cd(II) ions at the optimum condition and the nanofibers membrane shown the potentiality for possible use in efficient removal of the selected toxic ions from waste samples. Thus, the PVA/Chi NFs are considered to be effective and promising materials for Pb(II) and Cd(II) ions from wastewaters with high efficiency.

Pharmacokinetics of Dasatinib in Rats: a Potential Food-Drug Interaction with Naringenin.

BACKGROUND AND OBJECTIVES: The novel tyrosine kinase inhibitor (TKI) dasatinib, a multitarget inhibitor of Bcr-Abl and Src family kinases, has been licensed for the treatment of Ph+ acute lymphoblastic leukemia and chronic myeloid leukemia. Many citrus-based foods include the flavonoid naringenin, which is commonly available. Dasatinib is a Cyp3a4, P-gp, and Bcrp1 substrate, which makes it sensitive to potential food-drug interactions. The concurrent use of naringenin may change the pharmacokinetics of dasatinib, which could result in adverse effects and toxicity. The present investigation examined the impact of naringenin on the pharmacokinetics interactions of DAS and proposes a possible interaction mechanism in Wistar rats. METHODS: Rats were provided with a single oral dose of dasatinib (25 mg/kg) with or without naringenin pretreatment (150 mg/kg p.o. daily for 7 days, n = 6 in each group). Dasatinib was quantified in plasma by UHPLC MS/MS assay. Noncompartmental analysis was used to compute the pharmacokinetic parameters, and immunoblot was used to assess the protein expression in the hepatic and intestinal tissues. RESULTS: Following 7 days of naringenin pretreatment, the plasma mean concentration of dasatinib was enhanced compared with without pretreatment. In rats that were pretreated with naringenin, the pharmacokinetics of the orally administered dasatinib (25 mg/kg) was shown to be significantly different from that of dasatinib given without pretreatment (p < 0.05). There was a significant enhancement in pharmacokinetic parameters elimination half-life (T1/2), time to maximum concentration ( Tmax), maximum concentration )Cmax), area under the concentration-time curve (AUC0-t), area under the moment curve (AUMC0-∞), and mean residence time (MRT) by 28.41%, 50%, 103.54%, 72.64%, 115.08%, and 15.19%, respectively (p < 0.05) and suppression in elimination rate constant (Kel), volume of distribution (Vd), and clearance (CL) by 21.09%, 31.13%, and 46.25%, respectively, in comparison with dasatinib alone group (p < 0.05). The enhancement in dasatinib bioavailability and systemic exposure resulted from the significant inhibition of Cyp3a2, Mdr1/P-gp, and Bcrp1 expression and suppression of the dasatinib hepatic and intestinal metabolism, which enhanced the rate of dasatinib absorption and decreased its elimination. CONCLUSION: Concurrent use of naringenin-containing supplements, herbs, or foods with dasatinib may cause serious and potentially life-threatening drug interactions. Further studies are necessary to determine the clinical significance of these findings.

Effects of Orlistat or Telmisartan on the Serum Free Fatty Acids in Non-alcoholic Fatty Liver Disease Patients: An Open-Labeled Randomized Controlled Study.

BACKGROUND: One of the important inducers of inflammatory responses and accumulation of fat in hepatocytes is free fatty acids which ultimately lead to the development of non-alcoholic fatty liver disease. Patients with non-alcoholic fatty liver disease have high levels of plasma free fatty acids which are usually associated with type 2 diabetes and components of metabolic syndrome including dyslipidemia. Objective of this research is to investigate the effects of orlistat (a lipase enzyme inhibitor) or telmisartan (an angiotensin receptor blocker) on the serum free fatty acids in non-alcoholic fatty liver disease patients taking into consideration the baseline lipid profile. METHODS: This open-label clinical trial was carried out in the Department of Pharmacology, College of Medicine at the University of Sulaimani in cooperation with Shar Teaching Hospital in Sulaimani city-Kurdistan Region of Iraq. A total number of 74 non-alcoholic fatty liver disease patients were recruited and grouped randomly into group I (n = 25) treated with orlistat (120 mg/day orally) for 12 weeks, group II (n = 24) treated with telmisartan (20 mg/day orally) for 8 weeks, and group III (n = 25) treated with placebo (carboxy- methyl cellulose) once daily. Fasting serum level of free fatty acid and lipid profile including total cholesterol, triglyceride, high-density lipoprotein, and non-high-density lipoproteins were determined. RESULTS: Orlistat and telmisartan significantly reduced the triglyceride-glucose index and free fatty acid levels (P < .001) in patients with non-alcoholic fatty liver diseases. CONCLUSION: Short-term treatment with orlistat or telmisartan produce effective and significant reductions in FFAs in patients with non-alcoholic fatty liver disease compared to placebo. Orlistat effectively reduces the free fatty acid irrespective of the baseline lipid profile.

D-Dimer Level Among COVID-19 Patients as Biological Mediator for Hyper Coagulation State.

<b>Background and Objective:</b> Viremia due to SARS-CoV-2 lead variety of biochemical change in the human body, which play a crucial role in the activation of the coagulation cascade causing thrombotic complications and coagulopathies. The study aimed<i> </i>to ascertain the D-dimer level as a biological mediator in COVID-19 patients in Khartoum state and compare the results to the control group. <b>Materials and Methods:</b> A cross-sectional study was conducted during the period of August to December, 2021, including 50 healthy patients and 50 COVID-19 patients, blood samples were collected from study groups for measurement of D-dimer level using an I Chroma device. Statistical analysis was conducted using SSPS version 21. <b>Results:</b> This study revealed a statistically increased D-dimer level among COVID-19 patients compared with the control group (2000-10000 vs. up to 500 ng mL¹), respectively. <b>Conclusion:</b> Viremia induced by COVID-19 infection can cause a high D-dimer level which can lead to thrombosis event or bleeding tendency.

Is immunotherapy at reduced dose and radiotherapy for older patients with locally advanced non-small lung cancer feasible?-a narrative review by the international geriatric radiotherapy group.

Background and Objective: The standard of care for locally advanced non-small cell lung cancer (NSCLC) is either surgery followed by adjuvant chemotherapy with or without radiotherapy or concurrent chemotherapy and radiotherapy. However, older patients (70 years old or above) with multiple co-morbidities may not be able to tolerate the combined treatment due to its toxicity. Since lung cancer prevalence increases significantly with age, a new algorithm needs to be investigated to allow curative treatment for those with locally advanced disease. Methods: A literature search of the literature was conducted through PubMed and Google Scholar using search terms such as locally advanced NSCLC, older cancer patients, immunotherapy with check point inhibitors (CPI), and image-guided radiotherapy (IGRT). Abstracts were screened, full articles fitting the article topic were reviewed, and duplicated and non-English articles were excluded. Key Content and Findings: Recently, CPI has been introduced and proven effective for selected patients with increased program death ligand 1 (PD-L1) expression (50% or above). A reduced dose for CPI (RDCPI) may be as effective as a full dose and may decrease treatment cost. New radiation technique such as IGRT may also minimize radiotherapy complication through normal lung and cardiac sparing. Conclusions: IGRT and RDCPI may be an innovative option for older patients with locally advanced NSCLC and high PD-L1 expression and needs to be investigated in future prospective studies.

A Comparative Study of Safety Outcomes of Sodium Glucose Cotransporter-2 Inhibitors and Loop Diuretics Among Diabetic Patients Using Real-world Data.

Sodium glucose cotransporter-2 (SGLT2) inhibitors and loop diuretics can cause volume depletion. However, the long-term safety of the concurrent use of both agents has not been widely evaluated. We conducted a retrospective observational cohort study to evaluate the safety of SGLT2 inhibitors with loop diuretics vs SGLT2 inhibitors alone among diabetic patients. The primary endpoint was a composite of volume-depletion adverse events at 1 month and 12 months. Of the 400 patients included, 98 received SGLT2 inhibitors with a loop diuretic and 302 received SGLT2 inhibitors alone. The concurrent use of SGLT2 inhibitors and loop diuretics was tolerated at 1 month; however, it resulted in a significant increase in volume-depletion events at 12 months (10.2% vs 1.7%; aHR = 7.03, 95% CI (1.80-27.37), P-value = 0.005). In conclusion, the long-term concurrent use of SGLT2 inhibitors and loop diuretics increases the risk of volume depletion, warranting frequent monitoring.

Dichlorido{N-[1-(pyrazin-2-yl)ethyl-idene-κN]ethane-1,2-diamine-κN,N'}zinc.

The Zn(II) atom in the title complex, [ZnCl(2)(C(8)H(12)N(4))], is coordinated by two Cl atoms and three N atoms of the N-[1-(pyrazin-2-yl)ethyl-idene]ethane-1,2-diamine ligand, and displays a distorted square-pyramidal geometry with the apical position occupied by a Cl atom. In the crystal, inter-molecular N-H⋯Cl and C-H⋯Cl hydrogen bonds link the mol-ecules into a three-dimensional framework.

Hyperthyroidism precipitating cardiac arrest in a patient with Brugada pattern.

A 38-year-old man previously healthy suffered an out-of-hospital cardiac arrest; he was resuscitated successfully and admitted to the intensive care unit. His initial ECG suggested a Brugada pattern; other laboratory tests revealed low potassium level, low Thyroid Stimulating Hormone (TSH) and high FT4. He was started on carbimazole for hyperthyroidism, along with other supportive care. A comprehensive cardiac evaluation was done, including ajmaline and flecainide tests, results were inconclusive. An implantable cardioverter defibrillator device (ICD) was inserted to prevent such catastrophic events in the future. After discharge and on follow-up, our patient was doing well. His thyroid function test (TFT) was normal; moreover, a follow-up ICD interrogation did not record any arrhythmias. This case report highlighted asymptomatic hyperthyroidism as a precipitant for Brugada pattern resulting in sudden cardiac arrest.

Short-term orlistat therapy improves fatty infiltration indices and liver fibrosis scores in patients with non-alcoholic fatty liver disease and metabolic syndrome.

BACKGROUND AND STUDY AIMS: Patients with non-alcoholic fatty liver disease (NAFLD) exhibit features of metabolic syndrome, including a high body mass index, central obesity, high blood pressure, and abnormal lipid profile values. Orlistat, an intestinal lipase enzyme inhibitor, improves insulin resistance. We aimed to investigate the effects of short-term therapy with orlistat on the components of metabolic syndrome associated with NAFLD and explore its effect on liver fibrosis scores. PATIENTS AND METHODS: An open-label placebo-controlled clinical study using orlistat for 12 weeks was carried out on 50 patients with NAFLD. They were divided into a placebo group (Group I) and an orlistat treatment group (120 mg per day, Group II). The diagnosis of NAFLD was made by ultrasonography and laboratory investigations. Anthropometric and blood pressure measurements and hepatic liver enzymes, fasting lipids, and blood glucose levels were determined before and after treatment. Lipid indices including cholesterol (Chol-I), triglyceride (TG-I), triglyceride-glucose (TYG-I), and the scores for lipid fibrosis using the NAFLD fibrosis score (NFS) and Fibrosis-4 score (Fib-4) were also determined. RESULTS: Orlistat significantly improved the anthropometric and metabolic indices (TG-I, TYG-I) and liver enzymes. Orlistat demonstrated a favorable impact on the NAS and Fib-4 scores for liver fibrosis. CONCLUSION: Orlistat improves the components of metabolic syndrome, leading to the improvement of insulin resistance and thereby improves fatty infiltration of the liver. To a lesser extent, orlistat improved the liver fibrosis scores.

COVID-19 Management in a UK NHS Foundation Trust with a High Consequence Infectious Diseases Centre: A Retrospective Analysis.

Recent large national and international cohorts describe the baseline characteristics and outcome of hospitalised patients with COVID-19, however there is limited granularity to these reports. We aimed to provide a detailed description of a UK COVID-19 cohort, focusing on management and outcome. We performed a retrospective single-centre analysis of clinical management and 28-day outcomes of consecutive adult inpatients with SARS-CoV-2 PCR-confirmed COVID-19 from 31 January to 16 April 2020 inclusive. In total, 316 cases were identified. Most patients were elderly (median age 75) with multiple comorbidities. One quarter were admitted from residential or nursing care. Mortality was 84 out of 316 (26.6%). Most deaths occurred in patients in whom a ceiling of inpatient treatment had been determined and for whom end of life care and specialist palliative care input was provided where appropriate. No deaths occurred in patients aged under 56 years. Decisions to initiate respiratory support were individualised after consideration of patient wishes, premorbid frailty and comorbidities. In total, 59 (18%) patients were admitted to intensive care, of which 31 (10% overall cohort) required intubation. Multiple logistic regression identified associations between death and age, frailty, and disease severity, with age as the most significant factor (odds ratio 1.07 [95% CI 1.03-1.10] per year increase, p < 0.001). These findings provide important clinical context to outcome data. Mortality was associated with increasing age. Most deaths were anticipated and occurred in patients with advance decisions on ceilings of treatment.

Hyperthyroidism as a Precipitant Factor for Cerebral Venous Thrombosis: A Case Report.

Cerebral venous sinus thrombosis (CVT) is an uncommon yet serious condition. While CVT has many known precipitants and etiologies, hyperthyroidism as a precipitant of CVT is not well understood. This study reported a case of a 41-year-old male with a 4-year history of hyperthyroidism presented with seizure. Consequently, a diagnosis of superior sagittal sinus thrombosis was confirmed by computed tomography and magnetic resonance (MR) venograms. Extensive investigations yielded no apparent underlying cause, but laboratory findings were consistent with uncontrolled hyperthyroidism. The patient improved rapidly following anticoagulation. Follow-up MR and MRV scans 2 months after treatment revealed full recanalization of the superior sagittal sinus. This case report highlighted hyperthyroidism, as a procoagulant condition, resulting specifically in superior sagittal sinus thrombosis.

Ancient foe, serious weapon: Subarachnoid hemorrhage secondary to TB meningitis.

Tuberculosis is an ancient infectious disease with global distribution and a multitude of multisystem presentations. Infection of the central nervous system (CNS) is the most serious presentation manifested as tuberculous meningitis (TBM), intracranial tuberculoma, and tuberculous arachnoiditis all associated with significant morbidity and mortality. TBM is the commonest form of CNS manifestations capable of causing secondary arteritis leading to vascular complications. We report a case of a 22-year-old Indian patient diagnosed with TBM who subsequently presented with sudden onset severe headache, which was eventually diagnosed as subarachnoid hemorrhage. Radiological assessment confirmed secondary complications with cerebral aneurysmal dilatation attributed to TBM. The patient was safely managed with combined radiological and surgical interventions with uneventful outcomes. Review of the literature revealed that such complication of TBM is rare usually with serious implications. We aim to highlight to infection specialists to be aware of such association.

Case Report: Identification of Mutations in LAMP2 in Two Chinese Infants With Danon Disease.

Danon disease (DD) is a monogenic lysosomal storage disorder characterized by cardiomyopathy, skeletal myopathy, and variable degrees of intellectual disability. It is caused by a deficiency of lysosomal-associated membrane protein 2 (LAMP2). Two unrelated boys who presented with severe hypertrophic cardiomyopathy and elevated levels of liver enzymes, and were diagnosed with Danon disease at a very young age, were investigated. One boy was diagnosed at 4 months old and died soon after; his mother also died of hypertrophic cardiomyopathy shortly after his birth. Another developed hypertrophic cardiomyopathy at 3 months old but reported no significant cardiovascular symptoms during more than 5 years follow-up. Genetic screening found compound variants of LAMP2 and MYH7 in both of them. This report highlights the clinical heterogeneity in DD. The timely identification of LAMP2 mutation plays a critical role in their treatment and family counseling.

Nigella sativa Oil Mouth Rinse Improves Chemotherapy-Induced Oral Mucositis in Patients with Acute Myeloid Leukemia.

OBJECTIVE: The present study aims at evaluating the beneficial effect of Nigella sativa (NS) oil mouth rinse in the management of chemotherapy- (CT-) induced oral mucositis (OM) in patients with acute myeloid leukemia (AML). METHODS: Fifty-four AML patients were participated in this study and randomly allocated to either the test group or a control group. The patients of the test group received NS oil mouth rinse during 28-day CT, while the participants of the control group received a "magic mouthwash" formula. The primary outcome of this study was the incidence and severity of CT-induced OM in terms of erythema and ulcer. The secondary outcomes were the pain severity score, swallowing function, and the salivary concentrations of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). RESULTS: NS oil mouth rinse attenuated the progression of CT-induced OM compared with the control formula (AUC = 5.9 vs. 38.4, P < 0.05) and significantly decreased the erythema and ulceration scores (AUC of total OMAS = 11.4 vs. 85.9, P < 0.001) compared with the magic mouthwash formula. It also reduced the pain score and enabled all the participants of this group to consume normal food during treatment. It significantly decreased salivary IL-6 (AUC = 7376 vs. 16599, P < 0.001), while the changes of TNF-α levels were not significant (AUC = 676.9 vs. 885.2, P > 0.05). CONCLUSIONS: NS oil mouth rinse is effective in attenuating the severity of CT-induced OM and improves the pain and swallowing function in AML patients.

Do consumers who identify as Muslim experience culturally safe care (CSC) in the Emergency Department (ED)? A scoping review.

Lack of awareness about cultural and religious values and beliefs of patients presenting to Emergency Departments (ED) can compromise patient care and safety. Muslim Australians represent the fastest growing religious demographic group, with over a 77% growth in the last decade. The changing face of the Australian population requires that Australian health care carefully consider the dominant Western cultural paradigm currently influencing health care delivery. This predominance is particularly critical in the ED, as it is a common gateway into health care services. This scoping review explores the evidence of key components and impacts of culturally safe care (CSC) in the ED for staff and care consumers who identify as Muslim. A systematic search using electronic (five databases) and heading searching methods for primary research was undertaken; followed by a rigorous screening and quality appraisal process. Included articles were assessed for similarities and differences, and the subsequent content was grouped, synthesized and tested for clinical salience using the six stages of the Arksey and O'Malley methodological framework. The Mixed Method Assessment Tool was used to appraise the quality of included literature. Three studies were included in the analysis. Religious beliefs and practices are common among the individuals who identify as Muslim. Such beliefs and practices could influence patients' understanding of their conditions, their acceptance of care delivery, their processes of decision-making, and their commitment to treatment regimens and coping strategies. These ideals could also impact on a patient's care seeking behaviors and on family and community acceptance of care delivery. There is a serious lack of evidence around the delivery of culturally safe care in the ED locally and internationally. While many EDs may have procedure documents or staff care guidelines, it is unclear as to how these guides were derived, as there is minimal published evidence exploring any issues around provision of CSC to Muslim ED care consumers.