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Impact of Sodium Levels on Functional Outcomes in Patients With Stroke - A Swiss Stroke Registry Analysis.
Potasso, L, Refardt, J, De Marchis, GM, Wiencierz, A, Wright, PR, Wagner, B, Dittrich, T, Polymeris, AA, Gensicke, H, Bonati, LH, et al
The Journal of clinical endocrinology and metabolism. 2022;(2):e672-e680
Abstract
CONTEXT Correction of hyponatremia might represent an additional treatment for improving stroke patients' clinical outcomes. OBJECTIVE Admission hyponatremia is associated with worse clinical outcome in stroke patients, but whether normalization of hyponatremia improves outcome is unknown. We investigated whether normalization of hyponatremia affects patients' disability, mortality, and stroke recurrence within 3 months; length of hospitalization; and discharge destination. DESIGN This was a registry-based analysis of data collected between January 2016 and December 2018. We linked data from Swiss Stroke Registry (SSR) with electronic patients' records for extracting sodium values. SETTING We analyzed data of hospitalized patients treated at University Hospital of Basel. PATIENTS Stroke patients whose data and informed consent were available. MAIN OUTCOME MEASURE Modified Rankin Scale (mRS) score at 3 months. The tested hypothesis was formulated after SSR data collection but before linkage with electronic patients' records. RESULTS Of 1995 patients, 144 (7.2%) had hyponatremia on admission; 102 (70.8%) reached normonatremia, and 42 (29.2%) remained hyponatremic at discharge. An increase of initial sodium was associated with better functional outcome at 3 months (odds ratio [OR] 0.94; 95% CI, 0.90-0.99, for a shift to higher mRS per 1 mmol/L sodium increase). Compared with normonatremic patients, patients who remained hyponatremic at discharge had a worse functional outcome at 3 months (odds ratio 2.46; 95% CI, 1.20-5.03, for a shift to higher mRS). No effect was found on mortality, recurrence, or length of hospitalization. CONCLUSIONS In hospitalized acute stroke patients, persistent hyponatremia is associated with worse functional outcome. Whether active correction of hyponatremia improves outcome remains to be determined in prospective studies.
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Challenges of treatment adherence with direct oral anticoagulants in pandemic.
Dittrich, T, Polymeris, A, De Marchis, GM
Current opinion in neurology. 2021;(1):38-44
Abstract
PURPOSE OF REVIEW Direct oral anticoagulants (DOAC) are crucial for the prevention of thromboembolic events in patients with nonvalvular atrial fibrillation. Drug adherence by the patient but also adherence to guidelines by the physician are suboptimal. This review highlights aspects of DOAC treatment during the coronavirus disease 2019 (COVID-19) pandemic and selected challenging scenarios. RECENT FINDINGS For patients with a newly diagnosed indication for oral anticoagulation, a new interim clinical guidance recommends starting DOAC instead of vitamin K antagonists if DOAC are not contraindicated. The goal is to reduce the potential exposure of patients to severe acute respiratory syndrome coronavirus during the routine coagulation monitoring visits. As COVID-19 can lead to kidney failure, we discuss the challenges of DOAC dosing in kidney failures. Finally, we discuss two common challenges - when to start a DOAC after an ischemic stroke linked to atrial fibrillation, and whether cerebral microbleeds, including their count, are per se a contraindication to DOAC. SUMMARY There are still open challenges regarding DOAC treatment on the patient and physician side, both related and unrelated to the pandemic.
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3.
Oral Anticoagulants in Atrial Fibrillation Patients With Recent Stroke Who Are Dependent on the Daily Help of Others.
Meya, L, Polymeris, AA, Schaedelin, S, Schaub, F, Altersberger, VL, Traenka, C, Thilemann, S, Wagner, B, Fladt, J, Hert, L, et al
Stroke. 2021;(11):3472-3481
Abstract
BACKGROUND AND PURPOSE Data on the effectiveness and safety of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in patients with stroke attributable to atrial fibrillation (AF) who were dependent on the daily help of others at hospital discharge are scarce. METHODS Based on prospectively obtained data from the observational Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients-longterm registry from Basel, Switzerland, we compared the occurrence of the primary outcome—the composite of recurrent ischemic stroke, major bleeding, and all-cause death—among consecutive patients with AF-stroke treated with either VKAs or DOACs between patients dependent (defined as modified Rankin Scale score, 3–5) and patients independent at discharge. We used simple, adjusted, and weighted Cox proportional hazards regression to account for potential confounders. RESULTS We analyzed 801 patients (median age 80 years, 46% female), of whom 391 (49%) were dependent at discharge and 680 (85%) received DOACs. Over a total follow-up of 1216 patient-years, DOAC- compared to VKA-treated patients had a lower hazard for the composite outcome (hazard ratio [HR], 0.58 [95% CI, 0.42–0.81]), as did independent compared to dependent patients (HR, 0.54 [95% CI, 0.40–0.71]). There was no evidence that the effect of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome differed between dependent (HRdependent, 0.68 [95% CI, 0.45–1.01]) and independent patients (HRindependent, 0.44 [95% CI, 0.26–0.75]) in the simple model (Pinteraction=0.212). Adjusted (HRdependent, 0.74 [95% CI, 0.49–1.11] and HRindependent, 0.51 [95% CI, 0.30–0.87]; Pinteraction=0.284) and weighted models (HRdependent, 0.79 [95% CI, 0.48–1.31] and HRindependent, 0.46 [95% CI, 0.26–0.81]; Pinteraction=0.163) yielded concordant results. Secondary analyses focusing on the individual components of the composite outcome were consistent to the primary analyses. CONCLUSIONS The benefits of DOACs in patients with atrial fibrillation with a recent stroke were maintained among patients who were dependent on the help of others at discharge. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifier: NCT03826927.
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Acute Systemic Complications of Convulsive Status Epilepticus-A Systematic Review.
Sutter, R, Dittrich, T, Semmlack, S, Rüegg, S, Marsch, S, Kaplan, PW
Critical care medicine. 2018;(1):138-145
Abstract
OBJECTIVES Status epilepticus is a neurologic emergency with high morbidity and mortality requiring neurointensive care and treatment of systemic complications. This systematic review compiles the current literature on acute systemic complications of generalized convulsive status epilepticus in adults and their immediate clinical impact along with recommendations for optimal neurointensive care. DATA SOURCES We searched PubMed, Medline, Embase, and the Cochrane library for articles published between 1960 and 2016 and reporting on systemic complications of convulsive status epilepticus. STUDY SELECTION All identified studies were screened for eligibility by two independent reviewers. DATA EXTRACTION Key data were extracted using standardized data collection forms. DATA SYNTHESIS Thirty-two of 3,046 screened articles were included. Acute manifestations and complications reported in association with generalized convulsive status epilepticus can affect all organ systems fueling complex cascades and multiple organ interactions. Most reported complications result from generalized excessive muscle contractions that increase body temperature and serum potassium levels and may interfere with proper and coordinated function of respiratory muscles followed by hypoxia and respiratory acidosis. Increased plasma catecholamines can cause a decay of skeletal muscle cells and cardiac function, including stress cardiomyopathy. Systemic complications are often underestimated or misinterpreted as they may mimic underlying causes of generalized convulsive status epilepticus or treatment-related adverse events. CONCLUSIONS Management of generalized convulsive status epilepticus should center on the administration of antiseizure drugs, treatment of the underlying causes, and the attendant systemic consequences to prevent secondary seizure-related injuries. Heightened awareness, systematic clinical assessment, and diagnostic workup and management based on the proposed algorithm are advocated as they are keys to optimal outcome.
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5.
NAMPT pathway is involved in the FOXO3a-mediated regulation of GADD45A expression.
Thakur, BK, Lippka, Y, Dittrich, T, Chandra, P, Skokowa, J, Welte, K
Biochemical and biophysical research communications. 2012;(4):714-20
Abstract
Nicotinamide-phosphoribosyltransferase (NAMPT), induced under stress, converts nicotinamide (NA) to nicotinamide mononucleotide (NMN), which then reacts with ATP to regenerate NAD(+). Despite the pivotal role of NAD(+) in metabolic reactions, the molecular pathways triggered by the intracellular changes in NAD(+) level in cancer cells are largely unknown. Growth Arrest and DNA Damage-inducible Gene (GADD45A) is regulated by multiple cellular factors which play an important role in the control of cell-cycle checkpoint, DNA repair process and signal transduction. The present study was designed to assess the significance of intracellular NAD(+) levels on the regulation of GADD45A expression. The results of this study demonstrate an inverse relationship between NAMPT expression and the regulation of GADD45A gene. Thus, an overexpression of NAMPT led to a decreased expression of GADD45A, whereas, the inhibition of NAMPT by the known chemical inhibitor FK866 increased the expression of GADD45A in cells. Inhibition of SIRT1, an NAD(+)-dependent deacetylase, using shRNA also led to an increased expression of GADD45A gene. In further experiments we could show that the increased expression of GADD45A under the above experimental conditions, NAMPT inhibition by FK866, involves acetylation of FOXO3a, a member of the important family of forkhead (FOXO) proteins. This knowledge should contribute to our understanding of the role played by NAMPT and SIRT1 in the regulation of GADD45A expression by FOXO3a.