Mandrekar, Jay

Background & Purpose: Seizures are a recognized complication of stroke. However, available data are conflicting in terms of incidence, risk factors for occurrence, and impact on functional outcome and mortality. The aim of this study was to assess the incidence and characteristics of seizures following ischemic stroke in a well-defined population, and their effect on long-term patient outcome. Methodology: Utilizing the Rochester Epidemiology Project medical record linkage system, we identified all incident cases of ischemic stroke (IS) that occurred between January 1, 1990, and December 31, 1994. We identified all patients who developed seizures following first IS. Detailed data regarding stroke (including TOAST subtype, anatomic location, functional outcome), seizures (date, type, functional outcome, recurrence, presence of status epilepticus, complications, treatment, EEG findings), and patient status at the last follow-up were recorded and analyzed. Results: We identified 490 patients with first IS. Mean follow-up was 6.5 years (range 0.0 - 23.8). Of these, 35 (7.1%) developed seizures. Early seizures (occurring within 14 days of stroke) were present in 13 (37.1%), of which 9 (69.2%) had their seizure within the first 24 hours. Partial seizures were the most common type (23 patients, 65.7%). Status epilepticus occurred in two cases (5.7%). Tongue biting was the most common complication of poststroke seizures (4 patients, 11.4%). Treatment with antiepileptic drugs (AEDs) was initiated in 32 cases (91.4%). Only one drug was necessary for seizure control in all treated patients. The mean modified Rankin Scale score was 2.9 (SD 1.48) after the first IS, and worsened to 3.3 (SD 1.43) after the first seizure. Mortality at the last follow-up was higher in the seizure group compared to the non-seizure group, even after adjusting for TOAST subtype (HR 1.52; 95% CI 1.07 - 2.16; P = 0.02). Conclusion: Seizures are mostly a late complication of IS. They do not bear a high risk of life-threatening complications and are readily controllable by a single AED. However, patients who developed poststroke seizures tended to have a worse functional outcome and an increased mortality.

Background: Fever has been associated with worse clinical outcomes in aneurysmal subarachnoid hemorrhage (aSAH). However, the impact of the cause, severity, and duration of fever is not clear. We conducted this study to evaluate the impact of fever and subfebrile load and fever characteristics on functional outcome. Methods: We collected detailed information on fever onset, cause, severity, and duration during the ICU stay in a cohort of 586 consecutive patients with aSAH. Fever was defined as core body temperature ≥ 38.3°C. Subfebrile measurements were those between 37 and 38.2°C. Febrile and subfrebile loads were defined as number of hours with fever or subfebrile measurements. Poor outcome was defined as modified Rankin score (mRS) > 2. Univariate and multivariate logistic regression models were developed to define predictors of outcome using various categorizations of fever cause, severity, and duration. Results: 532/586 patients (90.9%) had fever for a mean of 2.1±3.0 days. Fever started within 24 hours in 69 (11.8%) and within 72 hours in 110 (18.8%). Poor outcome occurred in 175 patients (29.9%). On univariate analysis, days of fever, febrile load, fever onset within 24 hours, and fever onset within 72 hours were associated with poor outcome (all p<0.001), but subfebrile load was not (p=0.58). On multivariate model constructed with all variables associated with outcome on univariate analyses (including age, WFNS grade, modified Fisher grade) days of fever remained independently associated with poor outcome (OR 1.14 of poor outcome per day of fever, 95% CI 1.06-1.22; p=0.0006) displacing all other fever measures from the final model. Conclusions: The great majority of patients with aSAH are febrile during their ICU stay. Early onset of fever, number of hours with fever, and especially days of fever are associated with poor functional outcome. Conversely, the number of hours with elevated but subfebrile temperature does not influence clinical outcome. These data suggest that prolonged fever should be avoided, but subfebrile temperatures do not justify intervention.

Introduction: Obstructive sleep apnea (OSA) is an independent risk factor for ischemic stroke; however the causal mechanisms are unknown. Understanding etiology of stroke in OSA patients may: (1) aid in ascertaining how OSA exerts its influence in increasing stroke risk, and (2) facilitate tailoring recurrent stroke prevention management strategies in OSA patients. Our study compares stroke subtypes in OSA cases versus controls without significant sleep disordered breathing. Hypothesis: We hypothesized cardioembolic (CE) strokes would occur more frequently in OSA cases than in controls. Methods: Consecutive patients were identified who underwent polysomnography (PSG) at Mayo Clinic and suffered an ischemic stroke within one year after PSG. Patients with an apnea-hypopnea index (AHI) ≤ 10 were classified as controls; AHI > 10 classified as OSA cases. Mechanism of stroke was determined using (1) the Causative Classification System for Ischemic Stroke (CCS) and (2) the phenotype definitions used in the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Information on cardiovascular risk factors, neuroimaging, and echocardiography data were collected on each patient. Results: In 53 total subjects, CE strokes were more common among OSA cases (72% vs 33%, p=0.01). Large artery atherosclerosis and small vessel occlusion strokes were more common in controls. Atrial fibrillation (AF) was more frequent in OSA patients (59% vs 24%, p=0.01). Frequency of CE stroke increased with OSA severity. The association between OSA and CE stroke remained significant after controlling for AF (p=0.03, OR 4.5). Echocardiogram data revealed CE stroke risk factors were more frequent in OSA cases (84% vs 52% p=0.02). There were no significant differences between groups for left ventricular ejection fraction, left atrial volume index, or right ventricular systolic pressure. Conclusions: The results demonstrate a strong association between OSA and CE stroke. In OSA patients presenting with cryptogenic stroke, high clinical suspicion for cardioembolism is warranted. This may lead to consideration of further studies (eg, transesophageal echocardiography, Holter monitoring, or extended cardiac monitoring) to identify cardioembolic risk factors such as paroxysmal AF.

Background: Acute aortic syndrome (AAS) includes aortic dissection (AD), intramural hematoma (IMH) and penetrating aortic ulcer (PAU) and confers high rates of aortic related events. However, the risk of cardiovascular (CV) events in this patient group is unknown. The aim of this study was to define the rates of CV events in an incident cohort of AAS patients. Methods: Medical records and death certificates of all Olmsted County, MN residents with a diagnosis of AAS from 1995-2015 were reviewed and compared to age- and sex- matched population controls. Primary outcome was non-aortic CV mortality. Secondary outcome was overall mortality and first time non-fatal CV event (myocardial infarction (MI), heart failure (HF) or stroke). Events were analyzed using Cox proportional hazards regression adjusting for comorbidities. Results: Of 133 patients with AAS (77 AD, 21 IMH, 35 PAU) 57% were male, median age was 72 (SD 14) and median follow-up was 10 years. Overall survival in AAS cases and controls was 62% versus 83% at 5 years and 44% versus 60% at 10 years (adj HR 1.8, p<.001, 95% CI 1.3-2.4). CV death occurred in 21 (29%) of 73 AAS decedents due to HF (9), MI (5), other cardiac causes (5), stroke (1) and peripheral vascular disease (1). CV-related survival at 5 and 10 years after AAS diagnosis (91% and 81%) was not significantly different from controls (95% and 86%) after adjustment for comorbidities (adj HR 1.8, p=.1, 95% CI 0.9-3.6). AAS was associated with an increased risk of any first time CV event (adj HR 2.6, p<.001, 95% CI 1.6-4.4; Figure), first time diagnosis of MI (adj HR 2.8, p<.001, 95% CI 1.7-4.7) and HF (adj HR 3.2, p<.001, 95% CI 1.6-6.2) but not stroke. When excluding acute events within 14 days of diagnosis, AAS was still associated with a significantly higher mortality (adj HR 1.6, p=.011, 95% CI 1.1-2.4) and an increased risk of any first time CV event (adj HR 2.2, p=.018, 95% CI 1.1-4.1), first time MI (adj HR 2.2, p=.012, 95% CI 1.2-4.1) and HF (adj HR 2.9, p=.006, 95% CI 1.4-6.2) but not stroke. Conclusions: AAS is associated with a higher overall mortality and an increased risk of any first time CV event, first time MI and HF that persists beyond the acute phase. These data highlight the risk of CV events among those with AAS and implicate the need for long-term cardiovascular management in these patients.

Abstract The rapid spread of severe acute respiratory syndrome coronavirus 2 infection across the globe triggered an unprecedented increase in research activities that resulted in an astronomical publication output of observational studies. However, most studies failed to apply fully the necessary methodological techniques that systematically deal with different biases and confounding, which not only limits their scientific merit but may result in harm through misleading information. In this article, we address a few important biases that can seriously threaten the validity of observational studies of coronavirus disease 2019 (COVID-19). We focus on treatment selection bias due to patients’ preference on goals of care, medical futility and disability bias, survivor bias, competing risks, and the misuse of propensity score analysis. We attempt to raise awareness and to help readers assess shortcomings of observational studies of interventions in COVID-19.

Introduction: Acute stroke pre-arrival notification by emergency medical services (EMS) allows hospital personnel to mobilize resources in advance, thereby improving treatment times and outcomes. However, criteria for pre-arrival notification vary by institution. In developing our own pre-arrival notification system, we aimed to determine whether objective measures, EMS clinical impression, or a combination of both best predicted accurate stroke team activation. Methods: Retrospective review of consecutive patients presenting to our institution via EMS with suspicion of acute stroke from 2014-2015. Data recorded included age, gender, time of symptom onset, glucose, Cincinnati Prehospital Stroke Scale (CPSS), Glasgow Coma Scale (GCS), and EMS impression. Univariate logistic regression was performed with acute stroke team activation in the emergency department (ED) as the endpoint. Results: 130 patients met inclusion criteria. Of these, 88 prompted the ED provider to activate the acute stroke team. Of variables analyzed, CPSS was clinically and statistically significant (OR. 1.7, 95% CI 1.2-2.5, p=0.0035) on univariate analysis, with arm weakness being the most predictive component (OR 2.9, 95% CI 1.04-8.1, p=0.04). EMS impression was not statistically significant (p>0.05). We then performed sensitivity and specificity analyses of CPSS, EMS impression, and CPSS combined with EMS impression (Table). A CPSS score of 3 had the highest specificity, and CPSS score of 1 combined with EMS impression the highest sensitivity. Conclusion: CPSS was the key significant predictor of ED acute stroke team activation, and more specific than EMS clinical impression. By combining CPSS and EMS impression, sensitivity improved, but at the expense of specificity. This suggests that reproducible measurements and scores, such as CPSS, should be the main driver for stroke pre-notification systems and should be integrated systematically into EMS education programs.

Aims The aim of this study was to determine the diagnostic accuracy of α defensin (AD) lateral flow assay (LFA) and enzyme-linked immunosorbent assay (ELISA) tests for periprosthetic joint infection (PJI) in comparison to conventional synovial white blood cell (WBC) count and polymorphonuclear neutrophil percentage (PMN%) analysis. Methods Patients undergoing joint aspiration for evaluation of pain after total knee arthroplasty (TKA) or total hip arthroplasty (THA) were considered for inclusion. Synovial fluids from 99 patients (25 THA and 74 TKA) were analyzed by WBC count and PMN% analysis, AD LFA, and AD ELISA. WBC and PMN% cutoffs of ≥ 1,700 cells/mm3 and ≥ 65% for TKA and ≥ 3,000 cells/mm3 and ≥ 80% for THA were used, respectively. A panel of three physicians, all with expertise in orthopaedic infections and who were blinded to the results of AD tests, independently reviewed patient data to diagnose subjects as with or without PJI. Consensus PJI classification was used as the reference standard to evaluate test performances. Results were compared using McNemar’s test and area under the receiver operating characteristic curve (AUC) analysis. Results Expert consensus classified 18 arthroplasies as having failed due to PJI and 81 due to aseptic failure. Using these classifications, the calculated sensitivity and specificity of AD LFA was 83.3% (95% confidence interval (CI) 58.6 to 96.4) and 93.8% (95% CI 86.2 to 98.0), respectively. Sensitivity and specificity of AD ELISA was 83.3% (95% CI 58.6 to 96.4) and 96.3% (95% CI 89.6 to 99.2), respectively. There was no statistically significant difference between sensitivity (p = 1.000) or specificity (p = 0.157) of the two AD assays. AUC for AD LFA was 0.891. In comparison, AUC for synovial WBC count, PMN%, and the combination of the two values was 0.821 (sensitivity p = 1.000, specificity p < 0.001), 0.886 (sensitivity p = 0.317, specificity p = 0.011), and 0.926 (sensitivity p = 0.317, specificity p = 0.317), respectively. Conclusion The diagnostic accuracy of synovial AD for PJI diagnosis is comparable and not statistically superior to that of synovial WBC count plus PMN% combined. Cite this article: Bone Joint J 2021;103-B(6):1119–1126.