Correlations between serum kidney injury molecule-1, cystatin C and immunosuppressants: A cross-sectional study of renal transplant patients in Bahrain.

Renal transplant patients receive several immunosuppressive drug regimens that are potentially nephrotoxic for treatment. Serum creatinine is the standard for monitoring kidney function; however, cystatin C (Cys C) and kidney injury molecule-1 (KIM-1) have been found to indicate kidney injury earlier than serum creatinine and provide a better reflection of kidney function. Here, we assessed Cys C and KIM-1 serum levels in renal transplant patients receiving mycophenolate mofetil, tacrolimus, sirolimus, everolimus, or cyclosporine to evaluate kidney function. We used both the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation, which is based on creatinine and combined creatinine with Cys C, and the CKD-EPI 2012 equation, which is based on Cys C alone, to estimate glomerular filtration rate (GFR). Then, we assessed the association between serum KIM-1 and GFR < 90 mL/(min·1.73 m 2). We observed significantly higher serum Cys C levels in patients with the elevated serum creatinine, compared with those with normal serum creatinine. The estimated GFRs based on creatinine were significantly higher than those based on the other equations, while a significant positive correlation was observed among all equations. Serum KIM-1 levels were negatively correlated with the estimated GFRs by the CKD-EPI Cys C and the combined creatinine with Cys C equations. A serum KIM-1 level above 0.71 ng/mL is likely to indicate GFR < 90 mL/(min·1.73 m 2). We observed a significant correlation between serum creatinine and Cys C in our renal transplant patients. Therefore, serum KIM-1 may be used to monitor renal function when using potentially nephrotoxic drugs in renal transplants.

Secondary Prevention of Cryptogenic Stroke and Outcomes Following Surgical Patent Foramen Ovale Closure Plus Medical Therapy vs. Medical Therapy Alone: An Umbrella Meta-Analysis of Eight Meta-Analyses Covering Seventeen Countries.

Background: Cryptogenic stroke (CS) is an exclusion diagnosis that accounts for 10-40% of all ischemic strokes. Patent foramen ovale (PFO) is found in 66% of patients with CS, while having a prevalence of 25-30% in the general population. The primary aim was to evaluate the risk of recurrent stroke following surgical PFO closure plus medical therapy vs. medical therapy alone amongst CS, an embolic stroke of undetermined source (ESUS), or transient ischemic attack (TIA). The secondary aim was to evaluate new-onset non-valvular atrial fibrillation, mortality, and major bleeding. Methods: We conducted an umbrella meta-analysis using PRISMA guidelines on English studies comparing surgical PFO closure plus medical therapy versus medical therapy alone for managing CS. We extracted data on interventions and outcomes and used random-effects models with generic inverse variance to calculate relative risks (RRs) with 95% confidence intervals for outcome calculations. Results: A comprehensive search yielded 54,729 articles on CS and 65,001 on surgical PFO closure, with 1,591 studies focusing on PFO closure and medical therapy for secondary CS, ESUS, or TIA prevention. After excluding non-meta-analyses, 52 eligible meta-analyses were identified, and eight studies were selected for outcome evaluation, excluding non-English, non-human, and studies before January 2019 as of August 31, 2021. Among a total of 41,880 patients, 14,942 received PFO closure + medical therapy, while 26,938 patients received medical therapy alone. Our umbrella meta-analysis showed that PFO closure plus medical therapy had a 64% lower risk of recurrent strokes than medical therapy alone (pooled RR: 0.36). PFO closure plus medical therapy was associated with 4.94 times higher risk of atrial fibrillation. There was no difference in the risk of death or bleeding between both groups. Conclusion: In patients with CS, PFO closure, in addition to medical therapy, reduces the risk of recurrence. More research is needed to assess the efficacy of early closure as well as specific risk profiles that would benefit from early intervention to reduce the burden of stroke.

Prevalence and Outcomes of Depression, Obstructive Sleep Apnea, and Concurrent Anxiety (DOCA) in Stroke Survivors: Insights From a Nationwide Study.

BACKGROUND: Many individuals will also experience psychological side effects after a stroke episode, such as symptoms of depression, anxiety (generalized anxiety disorder (GAD)), and/or specific phobias, considerably decreasing their quality of life (QOL). OBJECTIVE: This study aimed to evaluate the prevalence of depression, obstructive sleep apnea (OSA), and concurrent anxiety (DOCA) and their outcomes (morbidity, disability (All Patient Refined Diagnosis Related Group (APRDRG) - loss of function), and discharge disposition) among acute ischemic stroke (AIS) hospitalizations. METHODS: A cross-sectional study used the National Inpatient Sample (NIS) from 2003-2017. Adults with hospitalizations with AIS were extracted, and DOCA was identified using ICD-9/10-CM codes. Weighted analysis using a chi-square test and mixed-effect multivariable survey logistic regression was used to assess the prevalence and role of DOCA in predicting outcomes. RESULTS: Out of 5,690,773 AIS hospitalizations, 2.7%, 3.1%, and 4.4% had depression, OSA, and GAD, respectively. In AIS patients, females had a higher prevalence of depression (3.4% vs. 2.3%) and GAD (5.9% vs. 3.0%) and a quality of life lower prevalence of OSA (2.2% vs 4.4%) in comparison to males (p<0.0001). Caucasians had a higher prevalence of depression, OSA, and GAD in comparison to others (African Americans/Hispanics/Asians/Native Americans). Depressed patients had a higher prevalence of morbidity (9% vs. 8% vs 5% vs. 7%), disability (46% vs. 46% vs. 35% vs. 37%), transfer to non-home (69% vs. 58% vs. 61% vs. 63%) in comparison with OSA, GAD, and non-DOCA patients, respectively (p<0.0001). Depression was associated with a 40% higher chance of severe disability (aOR 1.40; 95% CI 1.38-41), morbidity (1.36; 1.33-1.38), and discharge to non-home (1.54; 1.52-1.56). OSA and GAD had higher odds of non-home discharge amongst post-AIS hospitalizations. CONCLUSION: DOCA is associated with poor outcomes among post-AIS patients. Prompt recognition by screening and timely management of DOCA may mitigate the adverse outcomes.

Use of non-steroidal anti-inflammatory drugs in renal transplant patients: A retrospective study.

BACKGROUND: Renal transplants are often prescribed non-steroidal anti-inflammatory drugs (NSAIDs) for analgesic purposes. OBJECTIVE: Considering the dearth of data, we carried out the present study to evaluate the use of various NSAIDs and the incidence of acute kidney injury (AKI) in transplant patients. METHODS: A retrospective study amongst renal transplant patients prescribed at least one dose of NSAID was carried between January and December 2020 at the Department of Nephrology, Salmaniya Medical Complex, Kingdom of Bahrain. The patients' demographic details, serum creatinine values, and drug-related details were obtained. The Kidney Disease Improving Global Outcomes (KDIGO) criteria were used for defining AKI. RESULTS: Eighty-seven patients were included. Forty-three patients were prescribed diclofenac, 60 received ibuprofen, six received indomethacin, 10 were administered mefenamic acid, and 11 received naproxen. Due to multiple courses of NSAID prescription, a total of 70 prescriptions were identified for diclofenac, 80 for ibuprofen, six for indomethacin, 11 for mefenamic acid, and 16 for naproxen. No significant differences were observed in the absolute (p = 0.08) and percent changes in serum creatinine (p = 0.1) between the NSAIDs. Twenty-eight (15.2%) courses of NSAID therapy met the KDIGO criteria for AKI. Age (OR: 1.1, 95% CI: 1.007, 1.2; p = 0.02), concomitant everolimus (OR: 483, 95% CI: 4.3, 54407; p = 0.01), and mycophenolate + cyclosporine + azathioprine (OR: 63.4E+006, 95% CI: 203.2157 to 19.8E+012; p = 0.005) administration were observed with significant risk of NSAID-induced AKI. CONCLUSION: We observed possible NSAID-induced AKI to an extent of around 15.2% in our renal transplant patients. No significant differences were observed in the incidence of AKI between various NSAIDs and none of them had either graft failure or death.

Developing supervised machine learning algorithms to evaluate the therapeutic effect and laboratory-related adverse events of cyclosporine and tacrolimus in renal transplants.

BACKGROUND: Single nucleotide polymorphisms influence the effects of tacrolimus and cyclosporine in renal transplants. AIM: We set out to use machine learning algorithms (MLAs) to identify variables that predict the therapeutic effects and adverse events following tacrolimus and cyclosporine administration in renal transplant patients. METHOD: We sampled 120 adult renal transplant patients (on cyclosporine or tacrolimus). Generalized linear model (GLM), support vector machine (SVM), artificial neural network (ANN), Chi-square automatic interaction detection, classification and regression tree, and K-nearest neighbors were the chosen MLAs. The mean absolute error (MAE), relative mean square error (RMSE), and regression coefficient (ß) with a 95% confidence interval (CI) were used as the model parameters. RESULTS: For a stable dose of tacrolimus, the MAEs (RMSEs) of GLM, SVM, and ANN were 1.3 (1.5), 1.3 (1.8), and 1.7 (2.3) mg/day, respectively. GLM revealed that the POR*28 genotype and age significantly predicted the stable dose of tacrolimus as follows: POR*28 (ß -1.8; 95% CI -3, -0.5; p = 0.006), and age (ß -0.04; 95% CI -0.1, -0.006; p = 0.02). For a stable dose of cyclosporine, MAEs (RMSEs) of 93.2 (103.4), 79.1 (115.2), and 73.7 (91.7) mg/day were observed with GLM, SVM, and ANN, respectively. GLM revealed the following predictors of a stable dose of cyclosporine: CYP3A5*3 (ß -80.8; 95% CI -130.3, -31.2; p = 0.001), and age (ß -3.4; 95% CI -5.9, -0.9; p = 0.007). CONCLUSION: We observed that various MLAs could identify significant predictors that were useful to optimize tacrolimus and cyclosporine dosing regimens; yet, the findings must be externally validated.

A drug utilization and drug interaction study in renal transplant patients: Implications for an urgent need for drug deprescribing.

BACKGROUND: Renal transplant patients receive several drugs concomitantly. OBJECTIVE: Limited literature exists evaluating the drug use in this population that is at high risk for drug-induced acute kidney injury and complications due to under-or over-dosage of immunosuppressant drugs due to drug-drug interactions. METHODS: A retrospective observational study was carried out in 269 renal transplant patients in whom either oral or parenteral drugs were evaluated. World Health Organization (WHO) indicators of drug utilization such as the average number of drugs prescribed, daily defined dose, and proportion of drugs listed as WHO essential drugs were evaluated. Details on the drugs with nephrotoxic potential were obtained. Drug-drug interactions were assessed concerning the severity (major, moderate, and minor) as well as type (pharmacokinetic, pharmacodynamic, and toxicity). RESULTS: One-hundred and ninety-eight drugs were administered to the study participants. The median (range) total number of drugs received by the study participants was 23 (6-55). The proportion of drugs listed in the WHO essential drug database was 57.1 (16.7-100)%. Forty-six drugs with potential nephrotoxicity and seven drugs that were contra-indicated in patients with chronic renal disease/end-stage renal disease were administered to the study participants. The mean (SD) numbers of drug interactions observed amongst the study participants were 18.4 (10.1). Age (ß: 0.2, 95% CI: 0.1, 0.3) and duration of renal transplantation (ß: -0.3, 95% CI: -0.5, -0.1) were the significant predictors of drug burden. A total of 645 drug interactions were identified amongst the study participants (major - 240; moderate - 270; and minor - 135) of which the majority were pharmacokinetic followed by toxicity risk. Age was significantly associated with the risk of potential drug interaction (OR: 2.6, 95% CI: 1.8, 12.4; p = 0.001). CONCLUSION: Drug treatment in renal transplant patients poses a significant burden in terms of nephrotoxicity potential and drug-drug interactions. A dedicated ambulatory clinical pharmacy service monitoring the drug use coupled with drug deprescribing strategies are the need of the hour in this population.

Evaluation of the Association between Single Nucleotide Polymorphisms of Metabolizing Enzymes with the Serum Concentration of Paracetamol and Its Metabolites.

Intravenous paracetamol is a commonly administered analgesic and antipyretic in inpatient settings. Paracetamol is metabolized by cytochrome P450 (CYP) enzymes followed by conjugating enzymes to mainly glucuronide but to a lesser extent, sulphate metabolites, and oxidative metabolites. Single nucleotide polymorphisms (SNPs) in the CYP enzymes result in modified enzymatic activity. The present study was carried out to evaluate the prevalence of SNPs related to paracetamol metabolism and principal metabolites in critically ill patients, and those with chronic kidney disease. The present study is a cross-sectional study carried out in adults (>21 years) requiring intravenous paracetamol as part of their standard of care. Details regarding their demographics, and renal and liver function tests were collected. Blood was withdrawn for the analysis of paracetamol and their metabolites, and the SNPs of key CYP enzymes. Paracetamol/paracetamol glucuronide (P/PG), paracetamol/paracetamol sulphate (P/PS) and PG/PS were estimated. Acute liver injury (ALI) and renal dysfunction were defined using standard definitions. We observed a significant prevalence of SNPs in CYP1A2*1C, CYP3A4*3, CYP1A2*1K, CYP1A2*6, CYP2D6*10, and CYP2E1*2 amongst the 150 study participants. Those with CYP1A2*6 (CC genotype) were observed with significantly lower PG and PS concentrations, and a higher P/PS ratio; CYP2D6*10 (1/1 genotype) with a significantly lower PG concentration and a higher P/PG ratio; and CYP1A2*1K (CC genotype) was observed with a significantly higher PG/PS ratio. Good predictive accuracies were observed for determining the SNPs with the cut-off concentration of 0.29 µM for PS in determining CYP1A2*1K, 0.39 µM for PG and 0.32 µM for PS in determining CYP1A2*6 genotype, and 0.29 µM for PG in determining the CYP2D6*10 genotype. Patients with renal dysfunction were observed with significantly greater concentrations of paracetamol, PG and P/PS, and PG/PS ratios, with a lower concentration of PS. No significant differences were observed in any of the metabolites or metabolite ratios in patients with ALI. We have elucidated the prevalence of key CYP enzymes involved in acetaminophen metabolism in our population. Alterations in the metabolite concentrations and metabolic ratios were observed with SNPs, and in patients with renal dysfunction. Population toxicokinetic studies elucidating the dose-response relationship are essential to understand the optimized dose in this sub-population.

Long-Term Neurological Sequelae Among Severe COVID-19 Patients: A Systematic Review and Meta-Analysis.

Few studies have thoroughly evaluated the neuro-invasive effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which may contribute to a wide range of sequelae from mild long-term effects like headaches and fatigue to severe events like stroke and arrhythmias. Our study aimed to evaluate the long-term neurological effects of coronavirus disease 2019 (COVID-19) among patients discharged from the hospital. In this systematic review and meta-analysis, we assessed the long-term neurocognitive effects of COVID-19. Post-COVID-19 neurological sequelae were defined as persistent symptoms of headache, fatigue, myalgia, anosmia, dysgeusia, sleep disturbance, issues with concentration, post-traumatic stress disorder (PTSD), suicidality, and depression long after the acute phase of COVID-19. Data from observational studies describing post-COVID-19 neurocognitive sequelae and severity of COVID-19 from September 1, 2019, to the present were extracted following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol with a consensus of three independent reviewers. A systematic review was performed for qualitative evaluation and a meta-analysis was performed for quantitative analysis by calculating log odds of COVID-19 neurocognitive sequelae. The odds ratio (OR) and 95% confidence interval (CI) were obtained and forest plots were created using random effects models.  We found seven studies, out of which three were used for quantitative synthesis of evidence. Of the 3,304 post-COVID-19 patients identified, 50.27% were male with a mean age of 56 years; 20.20% had post-COVID-19 symptoms more than two weeks after the acute phase of infection. Among persistence symptoms, neurocognitive symptoms like headache (27.8%), fatigue (26.7%), myalgia (23.14%), anosmia (22.8%), dysgeusia (12.1%), sleep disturbance (63.1%), confusion (32.6%), difficulty to concentrate (22%), and psychiatric symptoms like PTSD (31%), feeling depressed (20%), and suicidality (2%) had a higher prevalence. In meta-analysis, COVID-19 patients with severe symptoms had higher odds of headache (pooled OR: 4.53; 95% CI: 2.37-8.65; p<0.00001; I2: 0%) and myalgia (pooled OR: 3.36; 95% CI: 2.71-4.17; p<0.00001; I2: 0%). Anosmia, fatigue, and dysgeusia had higher but non-significant odds following COVID-19. Although we had sufficient data for headache and fatigue to identify higher rates and associations following COVID-19, we could not establish relationships with other post-COVID-19 neurocognitive séqueles. Long-term follow-up may mitigate the neurocognitive effects among COVID-19 patients as these symptoms are also associated with a poor quality of life.

Effect Comparison of E-Cigarette and Traditional Smoking and Association with Stroke-A Cross-Sectional Study of NHANES.

Introduction: Tobacco use is one of the most significant risk factors for stroke. Besides traditional cigarettes and combustible products, the use of e-cigarettes and electronic nicotine delivery products has been widespread among young adults in the recent era. Furthermore, the trend of vaping has increased over the last decade. However, the relationship between e-cigarettes and stroke is largely unknown. The aim of this study was to evaluate the prevalence and identify the relationship between e-cigarette smoking and stroke. Methods: A cross-sectional study was performed using the NHANES database of the US population. Adults with a history of smoking were considered in our study and divided into three groups, e-cigarette users, traditional, and dual smokers. The Chi-squared test, Wilcoxon rank-sum test, and multivariable logistic regression analysis were used to identify the prevalence and association of e-cigarette consumption and stroke. Results: Out of a total of 266,058 respondents from 2015 to 2018, we found 79,825 respondents who smoked e-cigarettes (9.72%) or traditional (29.37%) or dual smoking (60.91%). Stroke prevalence among e-cigarette smokers was 1.57%. Stroke was more prevalent among traditional smokers than among e-cigarette smokers. (6.75% vs. 1.09%; p < 0.0001) E-cigarette smokers had early onset of stroke in comparison with traditional smokers. (median age: 48 vs. 59 years; p < 0.0001). Among females with stroke, the prevalence of e-cigarette use was higher in comparison with traditional smoking (36.36% vs. 33.91%; p < 0.0001). Among the stroke population, the prevalence of e-cigarette use was higher among Mexican-Americans (21.21% vs. 6.02%) and other Hispanics (24.24% vs. 7.70%) compared with traditional smoking (p < 0.0001). The regression analysis found higher odds of stroke history among e-cigarette users than traditional smokers [aOR: 1.15; 95% CI: 1.15−1.16)]. Conclusion: Though stroke was more prevalent in traditional smokers, the incidence of stroke was early-in-onset and was strongly associated with e-cigarette use compared to traditional smokers. We have also identified vascular effects of e-cigarettes components as possible triggers for the stroke.

Evaluation of Pharmacogenetics of Drug-Metabolizing Enzymes and Drug Efflux Transporter in Renal Transplants Receiving Immunosuppressants.

Cytochrome P450 (CYP) enzymes, such as CYP3A4, and CYP3A5, P450 oxidoreductase (POR), peroxisome proliferator activated receptor alpha (PPAR-alpha), and drug transporter (ABCB1) were observed to influence concentrations of immunosuppressants (cyclosporine, everolimus, sirolimus, and tacrolimus) and outcomes in renal transplants. We carried out the present study to evaluate the prevalence and impact of these single nucleotide polymorphisms (SNPs) in adult renal transplants. SNPs were evaluated using commercial TaqMan® assays. Serum drug concentrations were estimated using immunoassays. One hundred and forty-six patients were recruited. SNPs in CYP3A5*3 were significantly associated with greater dose-adjusted cyclosporine and tacrolimus concentrations. SNPs in POR*28 were observed with significantly lower dose-adjusted concentrations, particularly with cyclosporine and tacrolimus. ABCB1 homozygous polymorphisms were observed with significantly lower time spent in the therapeutic range with cyclosporine and everolimus/sirolimus. Cyclosporine was observed in a significantly greater proportion of patients with elevated GGT, and SNPs in PPAR-alpha were significantly associated with an increased risk of this adverse event. Hypertriglyceridemia with everolimus was significantly associated with POR*28 polymorphisms. There is a need to validate the influence of these SNPs in a prospective study and develop an algorithm predicting the achievement of target concentrations.

Diagnostic Yield of TEE in Patients with Cryptogenic Stroke and TIA with Normal TTE: A Systematic Review and Meta-Analysis.

INTRODUCTION: The role of transesophageal echocardiography (TEE) in cryptogenic stroke and transient ischemic attack (TIA) with normal transthoracic echocardiography (TTE) remains controversial in the absence of definite guidelines. We aimed to perform a systematic review and meta-analysis to estimate an additional diagnostic yield and clinical impact of TEE in patients with cryptogenic stroke and TIA with normal TTE. METHODS: We performed a systematic review of cohort studies on PubMed using the keywords 'cryptogenic stroke', cryptogenic TIA', 'TEE', and 'TTE' with matching MeSH terms. We included studies with patients who had cryptogenic stroke or TIA and had normal TTE findings, where the study intended to obtain TEE on all patients and reported all TEE abnormalities. The studies containing patients with atrial fibrillation were excluded. All studies were evaluated for internal and external validity. Inverse variance random effects models were used to calculate the effect size, the number needed to diagnose, and the 95% confidence interval. RESULTS: We included 15 studies with 2054 patients and found LA/LAA/aortic thrombus, valvular vegetation, PFO-ASA, valvular abnormalities, and complex aortic plaques on TEE. Of these, 37.5% (29.7%-45.1%) of patients had additional cardiac findings on TEE. Management of 13.6% (8.1%-19.1%) of patients had changed after TEE evaluation. Based on current guidelines, it should change management in 4.1% (2.1%-6.2%) of patients and could potentially change management in 30.4% (21.9%-38.9%) of patients. Sensitivity analysis was also performed with only class II studies to increase internal validity, which showed additional cardiac findings in 38.4% (28.5%-48.3%), changed management in 20.2% (8.7%-31.8%), should change management in 4.7% (1.5%-7.9%), and could potentially change management in 30.4% (17.8%-43.0%) of patients. CONCLUSIONS: The diagnostic yield of TEE to find any additional cardiac findings in patients with cryptogenic stroke or TIA is not only high, but it can also change management for certain cardiac abnormalities. TTE in cryptogenic stroke or TIA may mitigate future risks by tailoring the management of these patients.

Post-Hemorrhagic Hydrocephalus and Outcomes Amongst Neonates With Intraventricular Hemorrhage: A Systematic Review and Pooled Analysis.

Introduction Intraventricular hemorrhage (IVH) is a common cause of morbidity and mortality in preterm neonates. IVH leads to complications such as posthemorrhagic hydrocephalus (PHH), which commonly occurs in neonates with a more severe degree of IVH. Hence, we aimed to evaluate the characteristics and outcomes of PHH in neonates with IVH. Methods We performed a systematic review of cases reported from January 1978 to December 2020 through the PubMed database, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the keywords 'intraventricular hemorrhage,' 'cerebral intraventricular hemorrhage,' and 'newborn.' A total of 79 articles were considered for analysis, and data on neonatal and maternal characteristics and outcomes were collected. The analysis was performed by using the χ2 test, Wilcoxon rank-sum test, and multivariate logistic regression model. Results We analyzed a total of 101 IVH cases, 54.5% were male and 62.4% preterm. Thirteen point nine percent (13.9%) presented with grade I, 35.6% grade II, and grade III respectively, and 8% grade IV IVH. Among the 59 (58.4%) neonates with PHH, 33.6% had resolved PHH and 24.8% had unresolved. In adjusted regression analysis, we found that neonates with resolved PHH have lower odds of having neurodevelopmental delay (OR:0.15, 95%CI:0.03-0.74; p=0.02) and death (OR:0.9;95%CI:0.01-0.99; p=0.049) as compared to unresolved PHH. Conclusion Our study showed that neonates with resolved PHH have a statistically significant lower risk of neurodevelopmental delay (NDD) and mortality. Future studies should be planned to evaluate the role of treatment and its effect on outcomes in IVH neonates with PHH as a complication.

Risk Factors and Incidence of Acute Ischemic Stroke: A Comparative Study Between Young Adults and Older Adults.

Introduction Approximately 5-10% of strokes occur in adults of less than 45 years of age. The rising prevalence of stroke risk factors may increase stroke rates in young adults (YA). We aimed to compare risk factors and outcomes of acute ischemic stroke (AIS) among YA. Methods Adult hospitalizations for AIS and concurrent risk factors were found in the Nationwide Inpatient Sample database. Weighted analysis using chi-square and multivariable survey logistic regression was performed to evaluate AIS-related outcomes and risk factors among YA (18-45 years) and older patients. Results A total of 4,224,924 AIS hospitalizations were identified from 2003 to 2014, out of which 198,378 (4.7%) were YA. Prevalence trend of YA with AIS showed incremental pattern over time (2003: 4.36% to 2014: 4.7%; pTrend<0.0001). In regression analysis, the risk factors associated with AIS in YA were obesity (adjusted odds ratio {aOR}: 2.26; p<0.0001), drug abuse (aOR: 2.56; p<0.0001), history of smoking (aOR: 1.20; p<0.0001), infective endocarditis (aOR: 2.08; p<0.0001), cardiomyopathy (aOR: 2.11; p<0.0001), rheumatic fever (aOR: 4.27; p=0.0014), atrial septal disease (aOR: 2.46; p<0.0001), ventricular septal disease (aOR: 4.99; p<0.0001), HIV infection (aOR: 4.36; p<0.0001), brain tumors (aOR: 7.89; p<0.0001), epilepsy (aOR: 1.43; p<0.0001), end stage renal disease (aOR: 2.19; p<0.0001), systemic lupus erythematous (aOR: 3.76; p<0.0001), polymyositis (aOR: 2.72; p=0.0105), ankylosis spondylosis (aOR: 2.42; p=0.0082), hypercoagulable state (aOR: 4.03; p<0.0001), polyarteritis nodosa (aOR: 5.65; p=0.0004), and fibromuscular dysplasia (aOR: 2.83; p<0.0001). Conclusion There is an increasing trend in AIS prevalence over time among YA. Both traditional and non-traditional risk factors suggest that greater awareness is needed, with prevention strategies for AIS among young adults.

Outcomes of COVID-19 Complications and their Possibilities as Potential Triggers of Stroke.

INTRODUCTION: There is limited literature on coronavirus disease 2019 (COVID -19) complications such as thromboembolism, cardiac complications etc. as possible trigger for stroke. Hence, we aim to evaluate the prevalence and outcomes of COVID-19 related cardiovascular complications and secondary infection and their possibility as potential triggers for the stroke. METHODS: Data from observational studies describing the complications [acute cardiac injury (ACI), cardiac arrhythmias (CA), disseminated intravascular coagulation (DIC), septic shock, secondary infection] and outcomes of COVID-19 hospitalized patients from December 1, 2019 to June 30, 2020, were extracted following PRISMA guidelines. Adverse outcomes defined as intensive care units, oxygen saturation less than 90%, invasive mechanical ventilation, severe disease, and in-hospital mortality. The odds ratio and 95% confidence interval were obtained, and forest plots were created using random-effects models. A short review of these complications as triggers of stroke was conducted. RESULTS: 16 studies with 3480 confirmed COVID-19 patients, prevalence of ACI [38%vs5.9%], CA [26%vs5.3%], DIC [4%vs0.74%], septic shock [18%vs0.36%], and infection [30%vs12.5%] was higher among patients with poor outcomes. In meta-analysis, ACI [aOR:9.93(95%CI:3.95-25.00], CA [7.52(3.29-17.18)], DIC [7.36(1.24-43.73)], septic shock [30.12(7.56-120.10)], and infection [10.41(4.47-24.27)] had higher odds of adverse outcomes. Patients hospitalized with acute ischemic stroke and intracerebral hemorrhage, had complications like pulmonary embolism, venous thromboembolism, DIC, etc. and had poor outcomes CONCLUSION: The complications like acute cardiac injury, cardiac arrhythmias, DIC, septic shock, and secondary infection had poor outcomes. Patients with stroke were having history of these complications. Long term monitoring is required in such patients to prevent stroke and mitigate adverse outcomes.

Stroke and HIV-associated neurological complications: A retrospective nationwide study.

There is an increased risk of stroke and other neurological complications in human immunodeficiency virus (HIV) infected patients with no large population-based studies in the literature. We aim to evaluate the prevalence of stroke, HIV-associated neurological complications, and identify risk factors associated with poor outcomes of stroke among HIV admissions in the United States. In the nationwide inpatient sample with adult HIV hospitalizations, patients with primary cerebrovascular disease (CeVDs) and HIV-associated neurological complications were identified by ICD-9-CM codes. We performed a retrospective study with weighted analysis to evaluate the prevalence of stroke and neurological complications and outcomes of stroke among HIV patients. We included 1,559,351 HIV admissions from 2003 to 2014, of which 22470 (1.4%) patients had CeVDs (transient ischemic attack [TIA]: 3240 [0.2%], acute ischemic stroke [AIS]: 14895 [0.93%], and hemorrhagic stroke [HS]: 4334 [0.27%]), 7781 (0.49%) had neurosyphilis, 29,925 (1.87%) meningitis, 39,190 (2.45%) cytomegalovirus encephalitis, 4699 (0.29%) toxoplasmosis, 9964 (0.62%) progressive multifocal leukoencephalopathy, and 142,910 (8.94%) epilepsy. There is increased overall prevalence trend for CeVDs (TIA: 0.17%-0.24%; AIS: 0.62%-1.29%; HS: 0.26%-0.31%; pTrend < .0001) from 2003 to 2014. Among HIV admissions, variables associated with AIS were neurosyphilis (odds ratio: 4.38; 95% confidence interval: 3.21-5.97), meningitis (4.87 [4.10-5.79]), and central nervous system tuberculosis (6.72 [3.85-11.71]). Toxoplasmosis [4.27 [2.34-7.76]), meningitis (2.91 [2.09-4.06)], and cytomegalovirus encephalitis (1.62 [1.11-2.37]) were associated with higher odds of HS compared to patients without HS. There was an increasing trend of CeVDs over time among HIV hospitalizations. HIV-associated neurological complications were associated with the risk of stroke, together with increased mortality, morbidity, disability, and discharge to long-term care facilities. Further research would clarify stroke risk factors in HIV patients to mitigate adverse outcomes.

Newer Diagnostic and Cost-Effective Ways to Identify Asymptomatic Atrial Fibrillation for the Prevention of Stroke.

Atrial fibrillation (Afib) is the most common and underestimated cardiac arrhythmia with a lifetime risk of >35% after the age of 55 years and the risk continues to rise exponentially. Afib leads to stasis of blood within the atria allowing clot formation and increasing the risk for systemic embolization leading to strokes. Outcomes due to Afib can improve significantly with appropriate treatment. Thus, the need for convenient, well-tolerated, cost-effective cardiac monitoring for Afib is needed. The study aims to evaluate the various newer devices and compare them with traditional Holter monitoring, keeping diagnostic yield, cost-effectiveness, and patients' convenience in mind. Though Holter monitoring is simple and non-expensive, it has major limitations including limited recording capacity, inability for real-time recordings, and inconvenience to patients. Zio Patch (iRhythm Technologies, Inc; San Francisco, CA) and other loop recording devices are patient-friendly, inexpensive, and can offer real-time data for longer days. More prospective studies are needed to evaluate the sensitivity, specificity, and the actual number of patients getting benefits from newer devices by diagnosing Afib sooner and start early prevention therapy.

Prevalence and Outcomes Associated with Vitamin D Deficiency among Indexed Hospitalizations with Cardiovascular Disease and Cerebrovascular Disorder-A Nationwide Study.

Background: According to past studies, recovery and survival following severe vascular events such as acute myocardial infarction and stroke are negatively impacted by vitamin D deficiency. However, the national estimate on disability-related burden is unclear. We intend to evaluate the prevalence and outcomes of vitamin D deficiency (VDD) among patients with cardiovascular disease (CVD) and cerebrovascular disorder (CeVD). Methods: We performed a cross-sectional study on the Nationwide Inpatient Sample data (2016-2017) of adult (≥18 years) hospitalizations. We identified patients with a secondary diagnosis of VDD and a primary diagnosis of CVD and CeVD using the 9th revision of the International Classification of Diseases, clinical modification code (ICD-10-CM) codes. A univariate and mixed-effect multivariable survey logistic regression analysis was performed to evaluate the prevalence, disability, and discharge disposition of patients with CVD and CeVD in the presence of VDD. Results: Among 58,259,589 USA hospitalizations, 3.44%, 2.15%, 0.06%, 1.28%, 11.49%, 1.71%, 0.38%, 0.23%, and 0.08% had primary admission of IHD, acute MI, angina, AFib, CHF, AIS, TIA, ICeH, and SAH, respectively and 1.82% had VDD. The prevalence of hospitalizations due to CHF (14.66% vs. 11.43%), AIS (1.87% vs. 1.71%), and TIA (0.4% vs. 0.38%) was higher among VDD patients as compared with non-VDD patients (p < 0.0001). In a regression analysis, as compare with non-VDD patients, the VDD patients were associated with higher odds of discharge to non-home facilities with an admission diagnosis of CHF (aOR 1.08, 95% CI 1.07-1.09), IHD (aOR 1.24, 95% CI 1.21-1.28), acute MI (aOR 1.23, 95% CI 1.19-1.28), AFib (aOR 1.21, 95% CI 1.16-1.27), and TIA (aOR 1.19, 95% CI 1.11-1.28). VDD was associated with higher odds of severe or extreme disability among patients hospitalized with AIS (aOR 1.1, 95% CI 1.06-1.14), ICeH (aOR 1.22, 95% CI 1.08-1.38), TIA (aOR 1.36, 95% CI 1.25-1.47), IHD (aOR 1.37, 95% CI 1.33-1.41), acute MI (aOR 1.44, 95% CI 1.38-1.49), AFib (aOR 1.10, 95% CI 1.06-1.15), and CHF (aOR 1.03, 95% CI 1.02-1.05) as compared with non-VDD. Conclusions: CVD and CeVD in the presence of VDD increase the disability and discharge to non-home facilities among USA hospitalizations. Future studies should be planned to evaluate the effect of VDD replacement for improving outcomes.

Levels of protein C and soluble thrombomodulin in critically ill patients with acute kidney injury: a multicenter prospective observational study.

Endothelial dysfunction contributes to the development of acute kidney injury (AKI) in animal models of ischemia reperfusion injury and sepsis. There are limited data on markers of endothelial dysfunction in human AKI. We hypothesized that Protein C (PC) and soluble thrombomodulin (sTM) levels could predict AKI. We conducted a multicenter prospective study in 80 patients to assess the relationship of PC and sTM levels to AKI, defined by the AKIN creatinine (AKI Scr) and urine output criteria (AKI UO). We measured marker levels for up to 10 days from intensive care unit admission. We used area under the curve (AUC) and time-dependent multivariable Cox proportional hazard model to predict AKI and logistic regression to predict mortality/non-renal recovery. Protein C and sTM were not different in patients with AKI UO only versus no AKI. On intensive care unit admission, as PC levels are usually lower with AKI Scr, the AUC to predict the absence of AKI was 0.63 (95%CI 0.44-0.78). The AUC using log10 sTM levels to predict AKI was 0.77 (95%CI 0.62-0.89), which predicted AKI Scr better than serum and urine neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C, urine kidney injury molecule-1 and liver-fatty acid-binding protein. In multivariable models, PC and urine NGAL levels independently predicted AKI (p=0.04 and 0.02) and PC levels independently predicted mortality/non-renal recovery (p=0.04). In our study, PC and sTM levels can predict AKI Scr but are not modified during AKI UO alone. PC levels could independently predict mortality/non-renal recovery. Additional larger studies are needed to define the relationship between markers of endothelial dysfunction and AKI.

Can yoga be used to treat gastroesophageal reflux disease?

Yoga methods including Pranayama are the best ways to prevent many diseases and their progression. Even though, Yoga is widely practiced, its effects on certain medical conditions have not been studied or reported. Gastroesophageal reflux disease (GERD) is one of them. GERD is extremely common condition requiring frequent consumption of over-the-counter or prescribed proton pump inhibitors (PPI). In severe symptoms of GERD and in the presence of multiple etiologies, PPIs are insufficient to relieve the symptoms of gastric reflux. Regular and proper use of the Yoga along with PPI can control the severe symptoms of GERD and can avoid or delay the necessity of invasive procedures. This evidence-based case report focuses on the effects of Yoga on GERD. Our case report showed that regular practice of Kapalbhati and Agnisar kriya along with PPI, patients with hiatal hernia had improvement in severe symptoms of GERD, which were initially refractory to PPI alone.