Bilateral watershed infarcts due to hypoperfusion in the context of drug abuse: case report.

BACKGROUND: Watershed infarcts (WIs) are a distinct type of stroke with a varying clinical presentation that affects the border areas between the territories of two cerebral arteries and are typically associated with hemodynamic impairment and internal carotid artery stenosis. However, there is a paucity of data concerning its association with the history of recreational substance and drug abuse. METHODS/CASE REPORT: This case report presents a unique instance of bilateral internal watershed infarcts in a 23-year-old male with a history of polysubstance abuse, including methadone and cocaine. The patient's presentation included confusion, lower limb weakness, and systemic complications such as acute liver injury and myonecrosis, underlying the complexity of the clinical scenario. RESULTS: The investigation revealed no evidence of arterial stenosis or thrombosis, leading to the conclusion that the infarctions were likely precipitated by a total loss of consciousness due to substance abuse-related cerebral hypoperfusion and vasoconstriction. Methadone and cocaine, both implicated in vasoconstriction, lowering the seizure threshold and contributing to QTc prolongation, thus leading to loss of consciousness, were identified as potential triggers for the episode. CONCLUSIONS: In the young adult population, it is important to consider drug abuse as an etiological trigger for watershed infarcts, whereas the multi-system involvement and atypical presentation highlight the need for a comprehensive approach.

Protease-Activated Receptors (PARs): Biology and Therapeutic Potential in Perioperative Stroke.

Perioperative stroke is a devastating complication that occurs during surgery or within 30 days following the surgical procedure. Its prevalence ranges from 0.08 to 10% although it is most likely an underestimation, as sedatives and narcotics can substantially mask symptomatology and clinical presentation. Understanding the underlying pathophysiology and identifying potential therapeutic targets are of paramount importance. Protease-activated receptors (PARs), a unique family of G-protein-coupled receptors, are widely expressed throughout the human body and play essential roles in various physiological and pathological processes. This review elucidates the biology and significance of PARs, outlining their diverse functions in health and disease, and their intricate involvement in cerebrovascular (patho)physiology and neuroprotection. PARs exhibit a dual role in cerebral ischemia, which underscores their potential as therapeutic targets to mitigate the devastating effects of stroke in surgical patients.

High versus Medium Dose of Inhaled Corticosteroid in Chronic Obstructive Lung Disease: A Systematic Review and Meta-Analysis.

Background: Inhaled corticosteroids (ICSs) combined with bronchodilators have been identified to improve outcomes in COPD but also to be associated with certain adverse effects. Objective: We performed a systematic review and meta-analysis to compile and summarize data on the efficacy and safety of dosing levels (high versus medium/low) of ICS alongside ancillary bronchodilators following PRISMA guidelines. Data Sources: Medline and Embase were systematically searched until December 2021. Randomized, clinical trials (RCTs) that met predefined inclusion criteria were included. Data Extraction: Risk ratios (RRs) with 95% confidence intervals (CI) were extracted. Any acute exacerbation of COPD (AECOPD) risk was chosen as the primary efficacy outcome, mortality rate as the primary safety outcome, moderate/severe AECOPD risk as the secondary efficacy outcome and pneumonia risk as the secondary safety outcome. Subgroup analyses of individual ICS agents, of patients with baseline moderate/severe/very severe COPD and of patients with recent COPD exacerbation history were also performed. A random-effects model was used. Results: We included 13 RCTs in our study. No data on low doses were included in the analysis. High dose ICS was not associated with a statistically significant difference in any AECOPD risk (RR: 0.98, 95% CI: 0.91-1.05, I2: 41.3%), mortality rate (RR: 0.99, 95% CI: 0.75-1.32, I2: 0.0%), moderate/severe AECOPD risk (RR: 1.01, 95% CI: 0.96-1.06, I2: 0.0%) or pneumonia risk (RR: 1.07, 95% CI: 0.86 -1.33, I2: 9.3%) compared to medium dose ICS. The same trend was identified with the several subgroup analyses. Conclusion: Our study collected RCTs investigating the optimal dosing level of ICS prescribed alongside ancillary bronchodilators to patients with COPD. We identified that the high ICS dose neither reduces AECOPD risk and mortality rates nor increases pneumonia risk relative to the medium dose.

Safety of Direct Oral Anticoagulants for Gastrointestinal Hemorrhage in Patients With Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-analysis of Real-world Studies.

GOALS AND BACKGROUND: Since the introduction of Direct Oral Anticoagulants (DOACs), "real-world" studies have investigated their safety profile on gastrointestinal hemorrhage (GIH) when used by patients with Non-Valvular Atrial Fibrillation. We performed a systematic review and meta-analysis to compile and summarize this data after Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. STUDY: Medline and Embase were systematically searched until April 2021. Observational studies that met predefined inclusion criteria were included and hazard ratios (HRs) with 95% CI were extracted. Subgroup analyses based on DOAC doses, history of chronic kidney disease, stroke, prior exposure to VKA (vitamin K antagonist), age, gender, geographic location of population samples, as well as Leave-One-Out and Low/Moderate Risk of Bias sensitivity analyses were performed. A random effects model was used. RESULTS: A total of 46 studies were included. Apixaban was associated with a reduced risk of GIH compared with Dabigatran (HR: 0.67, 95% CI, 0.56 to 0.81, I2 : 53.28%), Rivaroxaban (HR: 0.56, 95% CI, 0.44 to 0.70, I2 : 79.17%), and VKA (HR: 0.68, 95% CI, 0.60 to 0.78, I2 : 71.93%). Rivaroxaban was associated with increased GIH risk compared with Dabigatran (HR: 1.19, 95% CI, 1.02 to 1.40, I2 : 72.96%) and VKA (HR: 1.16, 95% CI, 1.05 to 1.27, I2 : 81.95%). Dabigatran was associated with similar GIH risk compared with VKA (HR: 1.11, 95% CI, 0.98 to 1.26, I2 : 87.28%). CONCLUSIONS: Our study shows that Apixaban was associated with a reduction in GIH risk compared with Dabigatran, Rivaroxaban and VKA, whereas Rivaroxaban was associated with an increase in GIH risk compared with both Dabigatran and VKA.

B-Cell Targeted Therapies in Patients with Multiple Sclerosis and Incidence of Headache: A Systematic Review and Meta-Analysis.

BACKGROUND: Multiple Sclerosis treatment with B-cell targeted therapies may be associated with an increased incidence of headache. We aimed to find and compare the association of B-cell targeted therapies with the incidence of headache in patients with Multiple Sclerosis. METHODS: In a systematic based approach, the following databases were searched from inception until the 6th of June 2020: Pubmed/MEDLINE, ClinicalTrials.gov, EU Clinical Trials Register. Only randomized clinical trials (RCTs) enrolling patients with Multiple Sclerosis comparing B-cell targeted therapies (Rituximab, Ocrelizumab, Ofatumumab, Ublituximab or Cladribine) with placebo were selected for the systematic review and further meta-analysis. PRISMA guidelines were followed at all stages of the systematic review. The primary outcome was an all-cause headache of B-cell targeting therapy in patients with Multiple Sclerosis. RESULTS: Nine RCTs were included. Compared with placebo, treatment with B-cell targeting therapies revealed a trend in headache risk, but it was not statistically significant (Relative Risk 1.12 [95% Confidence Interval 0.96-1.30]; p = 0.15; I2 = 9.32%). Surprisingly, in a sub-group analysis, Cladribine was statistically significant for an increase in headache risk (RR 1.20 [95% CI 1.006-1.42]; p = 0.042; I2 = 0%; 3 studies with 2107 participants). CONCLUSIONS: Even though a trend is shown, B-cell targeted therapies do not correlate with an increased incidence of headache as an adverse effect. Sub-analyses revealed a significant association between Cladribine alone and an increased incidence of headache. Whereas a purinergic signaling cascade is proposed as a mechanism of action, further research is needed to unravel the underlying pathogenetic mechanism of headache induction and establish headache prevention strategies.

Effectiveness and safety of intracranial events associated with the use of direct oral anticoagulants for atrial fibrillation: A systematic review and meta-analysis of 92 studies.

AIMS: Observational studies have investigated the effectiveness and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) used in nonvalvular atrial fibrillation. We performed a systematic review and meta-analysis assessing the risk of ischaemic stroke, thromboembolism (TE) and intracranial haemorrhage (ICH) associated with the use of DOACs and VKAs. METHODS: Medline and Embase were systematically searched until April 2021. Observational studies were gathered and hazard ratios (HRs) with 95% confidence intervals (CI) were extracted. Subgroup analyses based on DOAC doses, history of chronic kidney disease, stroke, exposure to VKA, age and sex were performed. A random-effects model was used. RESULTS: We included 92 studies and performed 107 comparisons. Apixaban was associated with lower risk of stroke (HR: 0.82, 95% CI: 0.68-0.99) compared to dabigatran. Rivaroxaban was associated with lower risk of stroke (HR: 0.90, 95% CI: 0.83-0.98) compared to VKA. Dabigatran (HR: 0.85, 95% CI: 0.80-0.91), rivaroxaban (HR: 0.83, 95% CI: 0.77-0.89) and apixaban (HR: 0.75, 95% CI: 0.65-0.86) were associated with lower risk for TE/stroke compared to VKA. Apixaban (HR: 1.32, 95% CI: 1.03-1.68) and rivaroxaban (HR: 1.58, 95% CI: 1.31-1.89) were associated with higher risk of ICH compared to dabigatran. Dabigatran (HR: 0.48, 95% CI: 0.44-0.52), apixaban (HR: 0.60, 95% CI: 0.49-0.73) and rivaroxaban (HR: 0.73, 95% CI: 0.65-0.81) were associated with lower risk of ICH compared to VKA. CONCLUSION: Our study demonstrated significant differences in the risk of ischaemic stroke, TE/stroke and ICH associated with individual DOACs compared to both other DOACs and VKA.

Portopulmonary Hypertension: A Review of the Current Literature.

Portopulmonary hypertension is defined as the development of pulmonary arterial hypertension in the setting of portal hypertension with or without liver cirrhosis. Portal hypertension-associated haemodynamic changes, including hyperdynamic state, portosystemic shunts and splanchnic vasodilation, induce significant alterations in pulmonary vascular bed and play a pivotal role in the pathogenesis of the disease. If left untreated, portopulmonary hypertension results in progressive right heart failure, with a poor prognosis. Although Doppler echocardiography is the best initial screening tool for symptomatic patients and liver transplantation candidates, right heart catheterisation remains the gold standard for the diagnosis of the disease. Severe portopulmonary hypertension exerts a prohibitive risk to liver transplantation by conferring an elevated perioperative mortality risk. It is important for haemodynamic parameters to correspond with non-severe portopulmonary hypertension before patients can proceed with the liver transplantation. Small uncontrolled studies and a recent randomised controlled trial have reported promising results with vasodilatory therapies in clinical and haemodynamic improvement of patients, allowing a proportion of patients to undergo liver transplantation. In this review, the epidemiology, pathogenesis, diagnostic approach and management of portopulmonary hypertension are discussed. We also highlight fields of ongoing investigation pertinent to risk stratification and optimal patient selection to maximise long-term benefit from currently available treatments.

Dabigatran, rivaroxaban, and apixaban are superior to warfarin in Asian patients with non-valvular atrial fibrillation: An updated meta-analysis.

BACKGROUND: Most of the randomized clinical trials that led to the wide use of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with atrial fibrillation (AF) originated from western countries. AIM: To systematically review and quantitatively synthesize the real-world data regarding the efficacy and safety of dabigatran, rivaroxaban, and apixaban compared to warfarin for stroke prevention in Asian patients with non-valvular AF. METHODS: Medline, Cochrane, and ClinicalTrial.gov databases were reviewed. A random-effect model meta-analysis was used and I-square was utilized to assess the heterogeneity. The primary outcome was ischemic stroke. The secondary outcomes were all-cause mortality, major bleeding, intracranial hemorrhage, and gastrointestinal bleeding. RESULTS: Twelve studies from East Asia or Southeast Asia and 441450 patients were included. Dabigatran, rivaroxaban, and apixaban were associated with a significant reduction in the incidence of ischemic stroke [hazard ratio (HR) = 0.78, 95% confidence interval (CI): 0.65-0.94; HR = 0.79, 95%CI: 0.74-0.85, HR = 0.70, 95%CI: 0.62-0.78; respectively], all-cause mortality (HR = 0.68, 95%CI: 0.56-0.83; HR = 0.66, 95%CI: 0.52-0.84; HR = 0.66, 95%CI: 0.49-0.90; respectively), and major bleeding (HR = 0.61, 95%CI: 0.54-0.69; HR = 0.70, 95%CI: 0.54-0.90; HR = 0.58, 95%CI: 0.43-0.78; respectively) compared to warfarin. CONCLUSION: Dabigatran, rivaroxaban, and apixaban appear to be superior to warfarin in both efficacy and safety in Asians with non-valvular AF.

Venous thromboembolism in the era of COVID-19.

Coronavirus disease 2019 (COVID-19) does not only affect the respiratory system but appears to be a systemic disease. Venous thromboembolism is a common manifestation in hospitalized patients with COVID-19 with a reported incidence that is significantly higher compared to other acute viral infections. The pathophysiology mechanisms have not been fully explored and autopsy studies might enhance our understanding on this topic. Microthrombi formation occurs mainly in the pulmonary vasculature but can also occur in other organs. The high inflammatory burden related to COVID-19 seems to be associated with the coexisting coagulopathy. Concomitant manifestations of COVID-19, such as severe pneumonia, which has similar clinical presentation with pulmonary embolism (PE), and barriers related to strict isolation protocols are the two main reasons why PE diagnosis might be more challenging in patients with COVID-19. Medical societies have published guidance reports suggesting the administration of prophylactic anticoagulant therapy in hospitalized patients with COVID-19, but several questions regarding the optimal acute and long-term treatment of these patients remain unanswered.

Combination of low-dose glucocorticosteroids and mineralocorticoids as adjunct therapy for adult patients with septic shock: A systematic review and meta-analysis of randomized trials and observational studies.

BACKGROUND: The role of the combination of glucocorticosteroids and mineralocorticosteroids in treating septic shock is not well-defined. The aim of this study was to perform a systematic review and meta-analysis of the randomized controlled trials and observational studies assessing the effect of low-dose hydrocortisone and fludrocortisone on patients with septic shock. MATERIALS AND METHODS: MEDLINE, Scopus, and Cochrane databases were reviewed. A random effect model meta-analysis was used and I-square was used to assess the heterogeneity. Short-term mortality was chosen as our primary end point. A subgroup analysis was performed including only the randomized controlled trials. RESULTS: A total of 10,550 patients were included in this meta-analysis. Administration of the steroid combination was associated with improved short-term mortality (odds ratio, 0.78, confidence interval, 0.64-0.96), intensive care unit mortality, and shock reversal, without increase in steroid-related side effects, such as secondary infection or gastrointestinal hemorrhage. CONCLUSION: This systematic review and meta-analysis showed that use of the combination of glucocorticosteroids and mineralocorticosteroids has a beneficial impact on short-term mortality, intensive care unit mortality, and shock reversal, without increasing the incidence of gastrointestinal hemorrhage or superinfection in patients with septic shock, when used as an adjunct treatment to the established standard of care.