A co-occurrence between Sjogren's Disease (SjD) and Stiff Person Syndrome (SPS) is extremely rare, with only two prior case reports in the literature. This case series investigates this potential association. We present three cases with confirmed diagnosis of SPS and SjD. All the patients were evaluated and managed for both conditions in our institution. Three patients (2 females, 1 male; ages 59-71) were diagnosed with SPS and SjD. They met 2016 ACR/EULAR classification criteria for SjD. All the patients had positive serum anti-GAD65 antibodies, with one case showing anti-GAD65 antibodies in the CSF. In addition, at least one other autoimmune disorder was present in each case. The clinical manifestations of SPS preceded the onset of sicca symptoms by several years in all three cases. Patients demonstrated varying responses to therapy and the outcome was overall unfavorable. One patient underwent hematopoietic stem cell transplant for management of SPS, and two patients suffered major intracranial hemorrhages, one of which was fatal. This series suggests a possible association between SPS and SjD. Clinicians should maintain a high index of suspicion for this overlap to facilitate early diagnosis and management. Larger studies are needed to confirm this association.

A history of falls represents frailty in older adult patients. However, the influence of a history of falls on clinical outcomes in older adult non-valvular atrial fibrillation (NVAF) patients has not been fully elucidated. This All Nippon AF In the Elderly (ANAFIE) Registry sub-analysis evaluated the relationship between a history of falls within the year prior to the study's commencement and 2-year clinical outcomes in a large, older adult (aged ≥ 75years) Japanese population with NVAF. The ANAFIE Registry (UMIN000024006) was a multicenter, prospective, observational study with a 24-month follow-up period. Of the 32,275 enrolled patients, 28,664 with available fall history data were divided into two groups: those with and without a history of falls within the previous year (n = 2,347 and 26,317, respectively). Anticoagulant therapy was administered in 95% and 94% of these patients, respectively. Compared with patients without a history of falls, those with a fall history had higher incidences of stroke/systemic embolic events (2.59 vs. 1.52 per 100 person-years), major bleeding (2.20 vs. 0.96), intracranial hemorrhage (ICH) (1.71 vs. 0.66), cardiovascular death (2.12 vs. 0.97), all-cause death (6.78 vs. 3.34), and falls/fractures (13.52 vs. 5.44) (all, P < 0.001) during the follow-up period. In multivariable models, these associations remained significant for all outcomes. Notably, these clinical events, particularly major bleeding and ICH, were frequently observed after falls/fractures that occurred during the follow-up period. Compared with warfarin, direct oral anticoagulants were associated with significantly lower risks of new falls/fractures during the follow-up period, irrespective of baseline fall history. A history of falls within the previous year was associated with worse prognosis in older adult Japanese NVAF patients. Major bleeding (particularly ICH) occurred frequently following new occurrences of falls/fractures. Warfarin was associated with higher risks of subsequent falls/fractures. ANAFIE Registry was registered in the UMIN Clinical Trials Registry (identifier: UMIN000024006) on September 12, 2016.

Real-world comparative bleeding outcomes of direct oral anticoagulants versus warfarin in adults: Insights from observational evidence

Comparative safety and effectiveness of apixaban versus warfarin in antiphospholipid syndrome with chronic kidney disease: A real-world propensity-matched cohort study

Bleeding and thromboembolic events (BTE) increase the mortality of COVID-19 acute respiratory distress syndrome (ARDS) treated with extracorporeal membrane oxygenation (ECMO). The current analysis aimed to assess frequency and determinants of BTE according to their location and severity in a retrospective analysis of the German ECMO COVID-19 registry. Logistic regression was applied to identify factors influencing ICU survival as well as variables associated with risks of BTE. In total, 708 of 945 patients (75%) suffered from BTE. Overall, 1,348 events were registered, including 406 (30%) major bleeding and 258 (19%) major thromboembolic events. Most common major bleeding locations were intracranial (n = 133, 10%) and pulmonary bleeding (n = 116, 9%). In-ICU survival was 35, 46% without BTE and 22% with major bleeding (p < 0.05). In summary, major bleeding was a core outcome-determinant of COVID-19 ECMO mortality with intracranial major bleeding as the most devastating complication (OR: 5.3; CI: 2.9–9.9; p < 0.001). Neither major thromboembolism nor minor BTE impacted ICU-mortality. Potentially modifiable factors associated with major bleeding included prolonged duration of ECMO >14 days (OR: 2.9; CI 1.8–4.7; p < 0.001) and platelet counts <100.000/μL ≥ 72 h (OR: 2.0; CI 1.1–3.6; p = 0.018). Hence, prevention, early recognition and treatment of major bleedings are key to increase the survival of COVID-19 ECMO. In this regard, our data indicate that the implementation of early weaning strategies to minimize duration of ECMO therapy and prevention of prolonged thrombocytopenia with platelet counts <100.000/μl ≥ 72 h could decrease the risk of devastating bleeds and could ameliorate survival.Clinical trial registrationRegistered in the German Clinical Trials Register (study ID: DRKS00022964), retrospectively registered, September 7th 2020, https://drks.de/DRKS00022964.

Defining the risk of developing major bleeding, especially intracranial hemorrhage (ICH), or ischemic stroke (IS) in patients receiving antithrombotic therapy is crucial. Existing risk prediction tools would inadequately assess the net clinical benefit of antithrombotic therapy. We aimed to develop novel risk scores incorporating covert vascular brain injury to personalize the risk assessment of major bleeding, ICH, and IS in patients receiving antithrombotic therapy. The prospective, multicenter, observational study (BAT2 [Bleeding With Antithrombotic Therapy Study-2]) enrolled patients receiving oral antiplatelets or anticoagulants from 52 hospitals across Japan between 2016 and 2019. Multimodal brain magnetic resonance imaging was performed at baseline under prespecified conditions to determine cerebral small vessel disease (white matter hyperintensity, cerebral microbleed, lacune, enlarged perivascular space, and cortical superficial siderosis), nonlacunar infarct, and intracranial artery disease with central reading. Risk scores, collectively termed the BAT2 scores, were developed separately to evaluate the comparative risks of (1) major bleeding, (2) ICH, and (3) IS based on covariates from Cox proportional hazards models and clinical relevance. Model performance was assessed with the Harrell C-index and calibration slope adjusted for optimism via bootstrapping. Of 5378 patients enrolled, 5250 were analyzed (mean age, 71±11 years, 33% women); 93 experienced major bleeding, including 55 had ICH, and 197 had IS during a median follow-up of 2.0 years. Predictors for bleeding included age, underweight, renal impairment, hypertension, cerebral microbleed, lacune, and antithrombotic treatment type. Predictors for ICH further included deep white matter hyperintensity but not renal impairment. For IS, predictors included age, renal impairment, diabetes, atrial fibrillation, lacune, cerebral microbleed, nonlacunar infarct, and intracranial artery disease. Prediction performance showed optimism-adjusted C-index and calibration slope of 0.69 (95% CI, 0.64-0.74) and 0.82 (95% CI, 0.62-1.06) for bleeding, 0.75 (95% CI, 0.67-0.80) and 0.80 (95% CI, 0.56-1.02) for ICH, and 0.64 (95% CI, 0.60-0.68) and 0.92 (95% CI, 0.73-1.18) for IS. The BAT2 scores may help optimize the balance between risks and benefits of antithrombotic therapy. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02889653. URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000023669.

Impact of diagnostic coding schemas on major bleeding risk assessment for oral anticoagulants in patients with atrial fibrillation using administrative claims data.

Abstract BackgroundOral anticoagulants (OAC) can reduce ischemic stroke/systemic embolism (SSE) in patients with non‐valvular atrial fibrillation (AF) while increasing the risk of major bleeding. We aimed to analyze the number needed to treat for the net benefit (NNTnet) of warfarin and non‐vitamin K antagonist oral anticoagulants (NOACs).MethodsWe analyzed the results from multicenter national AF registry from 27 hospitals in Thailand. Follow‐up data were collected every 6 months until 3 years. Main outcomes were SSE, major bleeding, and intracranial hemorrhage (ICH). NNT was calculated from the absolute risk reduction (ARR) of SSE or absolute risk increase (ARI) of major bleeding or ICH. We compared NNTnet of warfarin versus no OAC, NOACs versus no OAC, and NOACs versus warfarin. Warfarin was also categorized into time in therapeutic range (TTR) &lt; and ≥65%.ResultsWe studied a total of 3405 patients (mean age 67.8 ± 11.3 years, 1424 (41.8%) were female). The incidence rates of SSE, major bleeding, and ICH were 1.51, 2.25, and 0.78 per 100 person‐years, respectively. Warfarin had negative NNTnet −37 compared to no OAC. NOACs had positive NNTnet 101 and 27 compared to no OACs and warfarin. Warfarin with TTR 65% had positive NNTnet 42 compared to no OAC. NOACs had comparable NNTnet as warfarin with TTR ≥65%.ConclusionWarfarin had a negative NNTnet compared to no OAC. Only warfarin with TTR 65% has positive NNTnet. NOACs had positive NNTnet compared to no OAC and when compared to warfarin.

Background: Direct-acting oral anticoagulants (DOACs) have emerged as a preferred alternative to Vitamin K Antagonists (VKAs) for patients with atrial fibrillation (AF). However, the exclusion of patients with liver cirrhosis (LC) from recent clinical trials leaves the efficacy and safety of DOACs in this population unclear. Hypothesis: DOACs are more effective and have a better safety profile compared to VKAs in patients with AF and LC. Methods: Following the PRISMA guidelines, we searched PubMed, Cochrane Library, Embase, Scopus, Web of Science, and CNKI databases for randomized clinical trials (RCTs) and observational studies comparing DOACs and VKAs in patients with AF and LC. Statistical analysis was performed using the metafor package in R software. Heterogeneity was assessed using the I2 statistic, and a random-effects model was employed to calculate pooled Hazard Ratios (HRs). For trivial heterogeneity (I2&lt;25%), a fixed-effect model was used. The confidence interval (CI) was set at 95%. Results: A total of one RCT and eight observational studies, encompassing 21903 patients, were included. Of these, 9882 patients were treated with DOACs and 11211 with VKAs. In 10105 patients with AF and LC, the incidence of major bleeding events was significantly lower in the DOAC group compared to the VKA group (HR 0.64; 95%CI 0.55-0.74; p&lt;0.001; I2=0%) (Figure 1A). The pooled adjusted effect estimates from multivariable analysis and inverse probability weighting for major bleeding were consistent (HR 0.71; 95%CI 0.61-0.82; p&lt;0.001; I2=7%) (Figure 1B). Additionally, the DOAC group exhibited lower rates of gastrointestinal (GI) bleeding (HR 0.76; 95%CI 0.69-0.85; p&lt;0.001; I2=18%) and intracranial hemorrhage (ICH) (HR 0.71; 95%CI 0.59-0.85; p&lt;0.001; I2=0%). There were no significant differences in thromboembolic events (Figure 2A) and all-cause mortality (Figure 2B) between the groups. Meta-regression analyses showed no significant impact of age, sex, follow-up duration, or baseline antiplatelet therapy on major bleeding events. Conclusion: In patients with AF and LC, DOACs are associated with a safer bleeding profile compared to VKAs, showing a reduced risk of major bleeding, GI bleeding, and ICH. However, no significant differences were observed in thromboembolic events or all-cause mortality. These findings suggest the potential of DOACs as a safer alternative in this patient population, warranting further validation through well-designed clinical studies.

Comparing Anticoagulation Strategies in Left Ventricular Assist Devices - Direct Oral Anticoagulants, No Anticoagulation, and Warfarin: A Case Series and Systematic Review of Literature

Many patients recruited in the Treatment of Brain Arteriovenous Malformations Study (TOBAS) are managed conservatively. The aim of this study was to monitor what happened to those patients. TOBAS comprises two randomized controlled trials and multiple prospective registries. All patients with brain arteriovenous malformations (AVMs) can participate. This report concerns patients selected for conservative management. The primary trial outcome measure is related death or dependency (modified Rankin Scale [mRS] score > 2) at 10 years. Secondary outcomes include intracranial hemorrhages, nonhemorrhagic neurological events, and serious adverse events (SAEs). For this report, outcome results are presented using patient-years, Kaplan-Meier survival curves, and Cox log-rank tests. There was no blinding. From June 2014 to May 2021, 1010 patients were recruited, of whom 498 (49%) were proposed the prospective observation registry. After exclusions, 434 (87%) patients remained for analysis. The majority of patients had unruptured AVMs (378/434 [87%]), of which 195 (52%) were low grade (Spetzler-Martin grade I or II). During a mean follow-up period of 3.2 years (total 1368 patient-years), the primary outcome occurred in 23 of 434 (5%) patients, corresponding to an incidence of 1.7 (95% CI 1.1-2.5) per 100 patient-years. For unruptured AVMs the incidence was 1.1 (95% CI 0.7-1.9) per 100 patient-years, and for low-grade unruptured AVMs it was 0.6 (95% CI 0.2-1.7) per 100 patient-years. Poor outcomes were more frequent in patients with a history of rupture (HR 5.6 [95% CI 2.4-13.0], p < 0.001), infratentorial AVMs (HR 2.9 [95% CI 1.1-7.3], p = 0.027), and age ≥ 55 years (HR 3.2 [95% CI 1.4-7.6], p = 0.007). Major intracranial hemorrhage occurred in 35 of 434 (8%) patients (incidence of 2.6 [95% CI 1.9-3.6] per 100 patient-years; 2.0 [95% CI 1.3-2.9] per 100 patient-years for unruptured AVMs and 1.3 [95% CI 0.6-2.6] per 100 patient-years for low-grade unruptured AVMs). Major AVM hemorrhages were more frequent in ruptured (HR 4.4 [95% CI 2.1-8.9], p < 0.001), large (HR 2.6 [95% CI 1.1-6.6], p = 0.039), and high-grade (HR 2.5 [95% CI 1.2-5.3], p = 0.013) AVMs and those with deep venous drainage (HR 2.1 [95% CI 1.1-4.2], p = 0.032). SAEs occurred in 48 of 434 (11%) patients (incidence of 3.6 [95% CI 2.7-4.8] per 100 patient-years). For unruptured AVMs the incidence was 2.8 (95% CI 2.0-4.0) per 100 patient-years, and for low-grade unruptured AVMs it was 1.8 (95% CI 1.0-3.2) per 100 patient-years. Nearly half of TOBAS participants were observed. Rates of untoward neurological events were within expected boundaries.

Andexanet alfa therapy showed No increased rate of thromboembolic events in spontaneous intracranial hemorrhage patients: A multicenter electronic health record study

Introduction: Atrial fibrillation (AF) and valvular heart disease (VHD) are common comorbidities, increasing the risk of thromboembolic events. While warfarin has been the standard for preventing stroke in AF patients, direct oral anticoagulants (DOACs) have emerged as an effective substitute. However, their safety and efficacy in VHD patients have yet to be established. Objective: To compare the effectiveness and safety of different DOAC agents versus warfarin in patients with AF and VHD in a network meta-analysis (NMA). Methods: We conducted an online search of databases for eligible studies from inception to April 2023. For dichotomous variables, we calculated the effect size using the risk ratio (RR) and its confidence interval (CI). We conducted frequentist and pairwise meta-analyses using the random-effects model in R-studio software. Results: Seven randomized controlled trials with 17533 patients were included in the review. Analysis of 6 studies showed that dabigatran 150 mg (RR 0.59, 95% CI [0.36, 0.98]) was associated with a lower risk of stroke compared to warfarin. Edoxaban 30 mg was associated with a significantly lower risk of major bleeding (RR 0.43, 95 CI [0.23, 0.81]). Compared to warfarin, dabigatran 110 mg (RR 0.29, 95% CI [0.13, 0.68]), edoxaban 30 mg (RR 0.30, 95% CI [0.11, 0.80]), dabigatran 150 mg (RR 0.36, 95% CI [0.17, 0.77]), edoxaban 60 mg (RR 0.37, 95% CI [0.15, 0.93]), and apixaban (RR 0.40, 95% CI [0.27, 0.61]), were associated with a significantly lower risk of intracranial hemorrhage (ICH). All DOACs did not show any difference in terms of all-cause or cardiovascular mortality, except for rivaroxaban Conclusion: In patients with AF and VHD, Edoxaban 30 mg is the safest DOAC agent associated with a reduced risk of major bleeding, ICH, and GI trouble. Dabigatran 150 mg is associated with a reduced risk of stroke and ICH but with a higher risk of GI trouble. However, Rivaroxaban is associated with an increased risk of systemic embolism.

Efficacy and Safety of Anticoagulation, Catheter-Directed Thrombolysis, or Systemic Thrombolysis in Acute Pulmonary Embolism

Risk of intracranial hemorrhage with direct oral anticoagulation versus low molecular weight heparin in the treatment of brain tumor-associated venous thromboembolism: A meta-analysis

For a precise diagnosis of infant hypoxic-ischemic encephalopathy (HIE), neuroimaging is required. The nature and time of the brain injury, the imaging modalities used, and the timing of their application all affect the therapeutic usefulness of neuroimaging in neonatal HIE. Most neonatal intensive care units (NICUs) across the world have access to cranial ultrasound (cUS), a safe, low-cost piece of technology that may be used at the patient's bedside.Infants undergoing active therapeutic hypothermia (TH) must undergo a cUS to be screened for intracranial hemorrhage (ICH), according to the clinical practice guidelines. The guidelines advise brain cUS on days 4 and 10-14 of life after hypothermia therapy is finished in order to thoroughly assess the nature and severity of any brain impairment. Early cUS is meant to rule out major ICH, which is listed in the local guideline for TH as a relative exclusion factor. This study questions whether cUS should be a required screening method before the start of TH.

Antiplatelet medications and intracranial hemorrhage in patients with primary brain tumors

Aortic stenosis (AS) is the most prevalent valvular disease in the elderlypopulation and the prevalence of atrial fibrillation (AF) increases in theelderly population. Transcatheter aortic valve replacement (TAVR) becomes animportant treatment for patients with AS at high surgical risk. This metanalysisaimed to compare the efficacy and safety of vitamin K antagonists (VKAs) anddirect oral anticoagulants (DOACs) in patients with AF undergoing TAVR. Wesearched the different databases for articles published before January 31, 2022.In total, 7 studies including 25,255 patients were analyzed. Data ondemographics, comorbidities, CHA2DS2-VASc score, Society of Thoracic Surgeons(STS) score, and incidences of all-cause mortality, major bleeding, intracranialhemorrhage (ICH), stroke, and thromboembolic events were obtained and analyzed.The VKA group had a lower CHA2DS2-VASc score (3.2 ± 1.2 vs 3.3 ± 1.2;P < .001) and a higher STS score (6.6 ± 3.2 vs6.1 ± 2.9; P < .001) than the DOAC group. The risks ofall-cause mortality (odds ratio [OR]: 0.88; 95% confidence interval [CI],0.67-1.16), ischemic stroke (OR: 1.06; 95% CI, 0.90-1.24), and thromboembolism(OR: 1.24; 95% CI, 0.63-2.47) in the DOAC group were comparable to the VKAgroup. The risks of major bleeding (OR: 0.77; 95% CI, 0.71-0.84) and ICH (OR:0.62; 95% CI, 0.42-0.90) were lower in the DOAC group compared to the VKA group.DOACs were associated with lower risks of major bleeding and ICH, and comparablerisks of all-cause mortality, ischemic stroke, and thromboembolism in patientswith AF undergoing TAVR compared to VKAs.

Risk of Intracranial Hemorrhage with Direct Oral Anticoagulants (DOACs) Versus Low Molecular Weight Heparin (LMWH) in Primary and Secondary Brain Cancers: An up-to-Date Meta-Analysis of Comparative Studies

Antiplatelet Medications and Intracranial Hemorrhage in Patients with Primary Brain Tumors