Background: and Purpose In the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial, treatment with nerinetide was associated with improved outcomes in patients who did not receive intravenous alteplase. We compared the effect of nerinetide on clinical outcomes in patients without concurrent intravenous alteplase treatment within different patient subgroups. Methods: ESCAPE-NA1 was a multicenter randomized trial in which acute stroke patients with baseline Alberta Stroke Program Early CT Score (ASPECTS) >4 undergoing endovascular treatment (EVT) were randomized to intravenous nerinetide or placebo. The primary outcome was independence (modified Rankin Scale [mRS] score 0–2) at 90 days. We assessed baseline, clinical, and imaging variables as predictors of outcome and for evidence of treatment effect modification. We constructed two multivariable models using variables known prior to randomization and variables known immediately post-EVT procedure to provide adjusted estimates of effect. We assessed for evidence of treatment effect modification using multiplicative interaction terms within each model. Results: Four hundred forty-six patients were included in the analysis. Clinical outcomes were better in patients randomized to the nerinetide arm (mRS 0–2: 59.4% vs. 49.8%). There was possible treatment effect modification by ASPECTS score; patients with ASPECTS 8–10 showed a larger treatment effect compared to those with lower ASPECTS score. Younger age, lower NIHSS score, lower baseline serum glucose, absence of atrial fibrillation at baseline, higher ASPECTS score, middle cerebral artery (vs. internal carotid artery) occlusion, use of conscious or no sedation (vs. general anesthesia), and faster treatment were all predictors of favorable outcome. Conclusion Patients in the nerinetide arm who were not treated with concurrent alteplase showed improved clinical outcomes and the treatment effect was larger among patients with favorable ASPECTS profiles.

Background: and Purpose In the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial, treatment with nerinetide was associated with improved outcomes in patients who did not receive intravenous alteplase. We compared the effect of nerinetide on clinical outcomes in patients without concurrent intravenous alteplase treatment within different patient subgroups. Methods: ESCAPE-NA1 was a multicenter randomized trial in which acute stroke patients with baseline Alberta Stroke Program Early CT Score (ASPECTS) >4 undergoing endovascular treatment (EVT) were randomized to intravenous nerinetide or placebo. The primary outcome was independence (modified Rankin Scale [mRS] score 0–2) at 90 days. We assessed baseline, clinical, and imaging variables as predictors of outcome and for evidence of treatment effect modification. We constructed two multivariable models using variables known prior to randomization and variables known immediately post-EVT procedure to provide adjusted estimates of effect. We assessed for evidence of treatment effect modification using multiplicative interaction terms within each model. Results: Four hundred forty-six patients were included in the analysis. Clinical outcomes were better in patients randomized to the nerinetide arm (mRS 0–2: 59.4% vs. 49.8%). There was possible treatment effect modification by ASPECTS score; patients with ASPECTS 8–10 showed a larger treatment effect compared to those with lower ASPECTS score. Younger age, lower NIHSS score, lower baseline serum glucose, absence of atrial fibrillation at baseline, higher ASPECTS score, middle cerebral artery (vs. internal carotid artery) occlusion, use of conscious or no sedation (vs. general anesthesia), and faster treatment were all predictors of favorable outcome. Conclusion Patients in the nerinetide arm who were not treated with concurrent alteplase showed improved clinical outcomes and the treatment effect was larger among patients with favorable ASPECTS profiles.

Background: and Purpose In the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial, treatment with nerinetide was associated with improved outcomes in patients who did not receive intravenous alteplase. We compared the effect of nerinetide on clinical outcomes in patients without concurrent intravenous alteplase treatment within different patient subgroups. Methods: ESCAPE-NA1 was a multicenter randomized trial in which acute stroke patients with baseline Alberta Stroke Program Early CT Score (ASPECTS) >4 undergoing endovascular treatment (EVT) were randomized to intravenous nerinetide or placebo. The primary outcome was independence (modified Rankin Scale [mRS] score 0–2) at 90 days. We assessed baseline, clinical, and imaging variables as predictors of outcome and for evidence of treatment effect modification. We constructed two multivariable models using variables known prior to randomization and variables known immediately post-EVT procedure to provide adjusted estimates of effect. We assessed for evidence of treatment effect modification using multiplicative interaction terms within each model. Results: Four hundred forty-six patients were included in the analysis. Clinical outcomes were better in patients randomized to the nerinetide arm (mRS 0–2: 59.4% vs. 49.8%). There was possible treatment effect modification by ASPECTS score; patients with ASPECTS 8–10 showed a larger treatment effect compared to those with lower ASPECTS score. Younger age, lower NIHSS score, lower baseline serum glucose, absence of atrial fibrillation at baseline, higher ASPECTS score, middle cerebral artery (vs. internal carotid artery) occlusion, use of conscious or no sedation (vs. general anesthesia), and faster treatment were all predictors of favorable outcome. Conclusion Patients in the nerinetide arm who were not treated with concurrent alteplase showed improved clinical outcomes and the treatment effect was larger among patients with favorable ASPECTS profiles.

This systematic review and meta-analysis aimed to examine the effect of the antioxidant alpha-lipoic acid (ALA) on various cardiometabolic risk factors and hormonal parameters in patients with polycystic ovary syndrome (PCOS). We searched PubMed, EMBASE, SCOPUS, Cochrane Library, and Web of Science databases without language restrictions until May 2023 to find randomized controlled trials (RCTs) that assessed the impact of ALA supplementation on anthropometric, glycemic, lipid, oxidative stress, and hormonal parameters in women with PCOS. Outcomes were summarized using the standardized mean difference (SMD) and 95% confidence interval (CI) in a random-effects model. An I2 statistic of >60% established significant between-study heterogeneity. The overall certainty of the evidence for each outcome was determined using the grading of recommendations, assessment, development, and evaluations system. Seven RCTs met the inclusion criteria. The ALA group had significant reductions in fasting blood sugar (fasting blood sugar (FBS), n=7 RCTs, SMD, -0.60; 95% CI, -1.10 to -0.10; I2=63.54%, moderate certainty of evidence) and homeostatic model assessment for insulin resistance (homeostatic model assessment of insulin resistance (HOMA-IR), n=4 RCTs, SMD, -2.03; 95% CI, -3.85 to -0.20; I2=96.32%, low certainty of evidence) compared with the control group. However, significant differences were observed between the groups in body mass index, insulin, estrogen, follicle-stimulating hormone, luteinizing hormone, testosterone, low-density lipoprotein, highdensity lipoprotein, triglyceride, total cholesterol, malondialdehyde, or total antioxidant capacity profiles. ALA supplementation improves FBS and HOMA-IR levels in women with PCOS. ALA consumption is an effective complementary therapy for the management of women with PCOS.

As a synthetic analog of codeine, tramadol is often prescribed to treat mild to moderate pains. This study was designed to estimate and compare the histological effect of tramadol on testes of both juvenile and adult male albino mice. A total number of 40 healthy male albino mice were classified into two main groups as follows: group I (juvenile group, includes 20 mice aged three weeks) subdivided equally into group Ia (control group received isotonic saline) and group Ib (tramadoltreated group received 40 mg/kg/d tramadol orally for 30 days); group II (adult group, includes 20 mice aged two months) subdivided equally into group IIa (control group received isotonic saline) and group IIb (tramadol-treated group). Juvenile and adult tramadol-treated groups showed numerous testicular changes, including blood vessels congestion, widening of intercellular spaces, vacuolization in interstitial tissues, luminal germ cells exfoliation, and increased expression of caspase-3 that indicated cellular apoptosis. In the ultrastructural examination, spermatogenic cells degenerated with the frequent appearance of apoptotic cells. Sertoli cells showed vacuolations, large lipid droplets, and disrupted intercellular cell junctions.These observed testicular changes were markedly observed in the juvenile group. Testicular abnormalities and apoptotic changes can be caused by tramadol administration. These abnormalities are more common in juvenile mice.

Background: and Purpose Various imaging paradigms are used for endovascular treatment (EVT) decision-making and outcome estimation in acute ischemic stroke (AIS). We aim to compare how these imaging paradigms perform for EVT patient selection and outcome estimation. Methods: Prospective multi-center cohort study of patients with AIS symptoms with multi-phase computed tomography angiography (mCTA) and computed tomography perfusion (CTP) baseline imaging. mCTA-based EVT-eligibility was defined as presence of large vessel occlusion (LVO) and moderate-to-good collaterals on mCTA. CTP-based eligibility was defined as presence of LVO, ischemic core (defined on relative cerebral blood flow, absolute cerebral blood flow, and cerebral blood volume maps) <70 mL, mismatch-ratio >1.8, absolute mismatch >15 mL. EVT-eligibility and adjusted rates of good outcome (modified Rankin Scale 0–2) based on these imaging paradigms were compared. Results: Of 289/464 patients with LVO, 263 (91%) were EVT-eligible by mCTA-criteria versus 63 (22%), 19 (7%) and 103 (36%) by rCBF, aCBF, and CBV-CTP-criteria. CTP and mCTA-criteria were discordant in 40% to 53%. Estimated outcomes were best in patients who met both mCTA and CTP eligibility-criteria and were treated with EVT (62% to 87% good outcome). Patients eligible for EVT by mCTA-criteria and not by CTP-criteria receiving EVT achieved good outcome rates of 53% to 57%. Few patients met CTP-criteria and not mCTA-criteria for EVT. Conclusions Simpler imaging selection criteria that rely on little else than detection of the occluded blood vessel may be more sensitive and less specific, thus resulting in more patients being offered EVT and arguably benefiting from it.

Background: The treatment of adult Burkitt lymphoma with pediatric-based chemotherapy protocols usually results in high cure rates, although with significant toxicity. We report our experience with the Cancer and Leukemia Group B1002 (CALGB 1002) protocol. Methods: The files of adult patients diagnosed with Burkitt lymphoma and treated with the CALGB 1002 protocol at King Hussein Cancer Center between 2008 and 2017 were reviewed.Baseline demographics, clinical laboratory features, treatment details, and responses were collected. The correlations between clinical and laboratory variables with event-free survival (EFS) and overall survival (OS) were determined by univariate and multivariate analyses using backward stepwise Cox regression models. EFS and OS were plotted using Kaplan‒Meier curves. Results: This study included 19 patients with a median age of 33 years (range, 19‒65). Eleven (58%) and two (10.5%) patients had advanced-stage and central nervous system disease, respectively. Among 106 administered cycles, the median interval between cycles was 23 days (range, 19‒84 days). Sixteen patients (84%) achieved a complete response. After a median follow-up of 40.8 months, the 3-year EFS and OS rates were 78.95%. Patients with a low-risk International Prognostic Index (IPI) had better survival than those with intermediate-or high-risk IPI. Grade III‒IV hematological toxicities occurred in 88% of patients, while 73% had grade III‒IV mucositis. Conclusion In adult Burkitt lymphoma, the CALGB 1002 protocol provides high cure rates and can be administered promptly, but is associated with significant toxicity. Risk-adapted approaches and other, less toxic, chemotherapeutic regimens should be considered.

Background: and Purpose Various imaging paradigms are used for endovascular treatment (EVT) decision-making and outcome estimation in acute ischemic stroke (AIS). We aim to compare how these imaging paradigms perform for EVT patient selection and outcome estimation. Methods: Prospective multi-center cohort study of patients with AIS symptoms with multi-phase computed tomography angiography (mCTA) and computed tomography perfusion (CTP) baseline imaging. mCTA-based EVT-eligibility was defined as presence of large vessel occlusion (LVO) and moderate-to-good collaterals on mCTA. CTP-based eligibility was defined as presence of LVO, ischemic core (defined on relative cerebral blood flow, absolute cerebral blood flow, and cerebral blood volume maps) <70 mL, mismatch-ratio >1.8, absolute mismatch >15 mL. EVT-eligibility and adjusted rates of good outcome (modified Rankin Scale 0–2) based on these imaging paradigms were compared. Results: Of 289/464 patients with LVO, 263 (91%) were EVT-eligible by mCTA-criteria versus 63 (22%), 19 (7%) and 103 (36%) by rCBF, aCBF, and CBV-CTP-criteria. CTP and mCTA-criteria were discordant in 40% to 53%. Estimated outcomes were best in patients who met both mCTA and CTP eligibility-criteria and were treated with EVT (62% to 87% good outcome). Patients eligible for EVT by mCTA-criteria and not by CTP-criteria receiving EVT achieved good outcome rates of 53% to 57%. Few patients met CTP-criteria and not mCTA-criteria for EVT. Conclusions Simpler imaging selection criteria that rely on little else than detection of the occluded blood vessel may be more sensitive and less specific, thus resulting in more patients being offered EVT and arguably benefiting from it.