Evaluation of a Pilot Spanish Language Program for Student Pharmacists.

OBJECTIVE: To present findings from an evaluation of the Spanish Language Track (SLT) for student pharmacists, which assessed student outcomes and feedback. METHODS: A mixed-methods program evaluation was conducted with the first cohort of the SLT members (N = 10). Participants completed pre/post-surveys and focus groups. Quantitative data analysis employed descriptive and frequency analysis, while qualitative data was thematically analyzed. RESULTS: With a focus on qualitative themes, quantitative results support themes one, two, and three based on findings from the self-assessment of participants' ability to speak and use the Spanish Language. Five themes were identified: (1) initial involvement and motivation to engage; (2) language skill development; (3) health-focused language immersion; (4) strong relationships within the SLT cohort; and (5) opportunities for improvement. CONCLUSION: Findings demonstrate students' active engagement with SLT while enhancing language skills through immersive experiences. Their connections with other cohort members, SLT team members, Colombian pharmacists, and bi-weekly patient appointment simulations were key contributors to learning outcomes while offering suggestions for programming. The SLT provides a foundational model for health professional programs to offer students opportunities to understand and practice language-concordant healthcare delivery to promote improved health outcomes in Spanish-speaking populations.

Mediation Analysis of Acute Carotid Stenting in Tandem Lesions: Effect on Functional Outcome in a Multicenter Registry.

BACKGROUND AND OBJECTIVES: Current evidence suggests that acute carotid artery stenting (CAS) for cervical lesions is associated with better functional outcomes in patients with acute stroke with tandem lesions (TLs) treated with endovascular therapy (EVT). However, the underlying causal pathophysiologic mechanism of this relationship compared with a non-CAS strategy remains unclear. We aimed to determine whether, and to what degree, reperfusion mediates the relationship between acute CAS and functional outcome in patients with TLs. METHODS: This subanalysis stems from a multicenter retrospective cohort study across 16 stroke centers from January 2015 to December 2020. Patients with anterior circulation TLs who underwent EVT were included. Successful reperfusion was defined as a modified Thrombolysis in Cerebral Infarction scale ≥2B by the local team at each participating center. Mediation analysis was conducted to examine the potential causal pathway in which the relationship between acute CAS and functional outcome (90-day modified Rankin Scale) is mediated by successful reperfusion. RESULTS: A total of 570 patients were included, with a median age (interquartile range) of 68 (59-76), among whom 180 (31.6%) were female. Among these patients, 354 (62.1%) underwent acute CAS and 244 (47.4%) had a favorable functional outcome. The remaining 216 (37.9%) patients were in the non-CAS group. The CAS group had significantly higher rates of successful reperfusion (91.2% vs 85.1%; p = 0.025) and favorable functional outcomes (52% vs 29%; p = 0.003) compared with the non-CAS group. Successful reperfusion was a strong predictor of functional outcome (adjusted common odds ratio [acOR] 4.88; 95% CI 2.91-8.17; p < 0.001). Successful reperfusion partially mediated the relationship between acute CAS and functional outcome, as acute CAS remained significantly associated with functional outcome after adjustment for successful reperfusion (acOR 1.89; 95% CI 1.27-2.83; p = 0.002). Successful reperfusion explained 25% (95% CI 3%-67%) of the relationship between acute CAS and functional outcome. DISCUSSION: In patients with TL undergoing EVT, successful reperfusion predicted favorable functional outcomes when CAS was performed compared with non-CAS. A considerable proportion (25%) of the treatment effect of acute CAS on functional outcome was found to be mediated by improvement of successful reperfusion rates.

Thrombectomy Outcomes in Acute Basilar Artery Occlusions Due to Intracranial Atherosclerotic Disease.

BACKGROUND AND OBJECTIVES: Intracranial atherosclerotic disease (ICAD) large vessel occlusion (LVO) is responsible for up to 30% of LVO. In this study, we aimed to determine the likelihood of favorable functional outcomes (modified Rankin Scale 0-3) in acute ICAD-LVO basilar occlusion compared with embolic basilar occlusion. METHODS: This is an analysis of the Posterior Circulation Ischemic Stroke Evaluation: Analyzing Radiographic and Intraprocedural Predictors for Mechanical Thrombectomy Registry in which patients with acute basilar artery occlusions from 8 comprehensive stroke centers were included from 2015 to 2021. Patients were dichotomized into with (ICAD-LVO) or without underlying ICAD (embolic). Descriptive statistics for each group and multivariate logistic analysis were performed on the primary outcome. RESULTS: Three hundred forty-six patients were included. There were 215 patients with embolic (62%) and 131 patients with ICAD-LVO (38%). Baseline demographics were equivalent between the 2 groups except for sex (male 47% vs 67%; P < .001), history of stroke (12% vs 25%; P = .002), and atrial fibrillation (31% vs 17%; P = .003). At 90 days, patients in the ICAD-LVO cohort were less likely to achieve favorable functional outcomes (odds ratio [OR] 0.41, 95% CI 0.22-0.72; P = .003) after adjusting for potentially confounding factors. In addition, ICAD-LVO strokes were less likely to achieve thrombolysis in cerebral infarction ≥2b (OR 0.29, 95% CI 0.14-0.57; P < .001). ICAD-LVO lesions were more likely to require stent placement (OR 14.94, 95% CI 4.91-45.49; P < .001). Subgroup analysis demonstrated favorable functional outcomes in patients who underwent stenting and angioplasty compared with failed recanalization cohort (OR 4.96, 95% CI 1.68-14.64; P < .004). CONCLUSION: Patients with acute basilar ICAD-LVO have higher morbidity and mortality compared with patients with embolic source. Lower rates of successful recanalization in the ICAD-LVO cohort support this finding. Our subgroup analysis demonstrates that stenting should be considered in patients with recanalization failure. Rates of symptomatic intracranial hemorrhage were similar between the ICAD-LVO and embolic cohorts.

Pharmacotherapeutic value of inflammatory and neurotrophic biomarkers in bipolar disorder: A systematic review.

BACKGROUND: The various pharmacological interventions, ranging from mood stabilizers and antipsychotics to antidepressants, reflect the diff/iculty of treating depressive/manic symptomatology of bipolar disorder (BD). Among a broad range of mechanisms implicated, immune dysregulation may contribute to the increased inflammation that influences the course of BD. Inflammatory, neurotrophic and oxidative stress factors may be identified as promising peripheral biomarkers in brain functioning, perhaps serving as predictors of an effective response to treatment for BD. The present systematic review aimed to examine the evidence supporting the pharmacotherapeutic value of inflammatory and neurotrophic biomarkers in BD. METHODS: PubMed, PsychINFO, Scopus and Web of Science were searched from inception to May 2024 by two independent reviewers. A total of 40 studies with 3371 patients with diagnosis and intervention of BD were selected. RESULTS: Inconsistencies in the effects of pharmacological treatments on the connection between the expected anti-inflammatory response and symptomatologic improvement were identified. Mood stabilizers (lithium), antipsychotics (quetiapine), antidepressants (ketamine) or their combination were described to increase both pro-inflammatory (TNFα, IL-6) and anti-inflammatory (IL-4, IL-8) factors. Other medications, such as memantine and dextromethorphan, autoimmune (infliximab) non-steroidal anti-inflammatory (aspirin, celecoxib) drugs, antidiabetics (pioglitazone), and even dietary supplementation (omega-3), or their combination, clearly decrease inflammatory factors (TNFα, IL-6, IL-1ß, C-reactive protein) and/or increase the neurotrophic factor BDNF in BD patients. CONCLUSION: Inflammation in BD requires further investigation to understand the underlying immunologic mechanism, to identify predictors of treatment response, and to make informed decisions about the use and development of more effective pharmacological interventions for BD.

Minimally Invasive Technique for Chiari I Decompression Without Durotomy: Surgical Technique and Preliminary Case Series.

BACKGROUND: Chiari I malformation, marked by severe headaches and potential brainstem/spinal cord issues, often requires surgical intervention when conservative methods fail. This study introduces a minimally invasive surgery (MIS) Chiari decompression technique utilizing a 3-blade retractor, aiming to reduce postoperative discomfort and optimize outcomes. METHODS: Chiari type I malformation patients who underwent a MIS technique were included. Technique consisted of a minimal-soft tissue opening using a 3-blade retractor, suboccipital craniectomy, C1 laminectomy, and resection of the atlantooccipital band without a durotomy. RESULTS: Ten patients were treated. Mean age was 43.3 years, with 7 female patients. All patients presented with occipital headaches; 50% retroorbital pain; 40% neck, upper back, or shoulder pain; and 30% limb paresthesias. Median pre-surgical modified Rankin Scale (mRS) was 3 (2-4) and pain visual analog score (VAS) was 7 (5-9). Mean operative time was 59 (59-71) minutes, with mean blood loss of 88.5 (50-140) mL. In our sample, 90% of patients were discharged the same surgical day (mean 7.2 [5.3-7.7] hours postoperative). No immediate or delayed postoperative complications were evidenced. At 6 months, 90% of patients had mRS 0-1. At last follow-up the mean VAS was 1.5 (range: 0-4, P < 0.001). CONCLUSIONS: The MIS 3-blade flexible retractor technique for Chiari decompression is feasible, provides wide visualization angles of the suboccipital region and C1 arch, allows 2-surgeon work, and minimizes skin and soft tissue disruption. This combination may diminish postoperative discomfort, reduce the risk of surgical site infections, and optimize outcomes.

Locking Attachment Plate for the Surgical Treatment of Periprosthetic and Periimplant Fractures: Long-Term Follow-Up.

Objectives: The surgical management of periprosthetic fractures (PPF) and periimplant fractures (PIF) can be challenging. The locking attachment plate (LAP) was proposed in recent years for the osteosynthesis of such fractures. The aim of this study was to assess the experience of a third-level hospital with LAP for the treatment of PPF and PIF, and analyse the clinical outcomes. Methods: Data were prospectively collected and analysed from all patients whose PPF/PIF was treated surgically with LAP in a third-level hospital from June 2018 to June 2022. All fractures were postoperative low-energy femur fractures. The minimum follow-up period was six months. Results: Thirty-eight patients (31 women) met the eligibility criteria. The mean age was 86.3 years. The median time until surgery was 4 days. A mean of 3.61 screws were used for each LAP. The mean femur plate length was 14 holes, and the mean working length 7.1 holes. The median hospital stay was nine days. The mean follow-up was 19.56 months. At one month, 12 patients tolerated partial weight-bearing. Five patients walked independently indoors. One patient had died and seven patients were readmitted. At six months, six more patients had died. Fifteen patients tolerated full weight-bearing (FWB). Nine patients walked independently indoors, six outdoors. Twenty-five patients reached fracture consolidation without malalignment. Nine patients were readmitted. At 12 months, another patient had died. Seventeen patients tolerated FWB. Eleven patients walked independently indoors, six outdoors. Twenty-five patients achieved fracture consolidation without malalignment. Five patients were readmitted. Fourteen patients crossed the two-year postoperative threshold. All achieved fracture consolidation. Two patients passed the 4-year postoperative milestone. Conclusion: The clinical results of patients whose PPF or PIF was treated with the LAP are promising. This fixation method is a viable option to be considered when planning surgery for such fractures.

Hydroxytyrosol Linoleoyl Ether Ameliorates Metabolic-Associated Fatty Liver Disease Symptoms in Obese Zucker Rats.

A main hepatic consequence of obesity is metabolic-associated fatty liver disease (MAFLD), currently treated by improving eating habits and administrating fibrates yet often yielding suboptimal outcomes. Searching for a new therapeutic approach, we aimed to evaluate the efficacy of hydroxytyrosol linoleoyl ether (HTLE), a dual Ppar-α agonist/Cb1 antagonist with inherent antioxidant properties, as an antisteatotic agent. Using lean and obese Zucker rats, they were administrated daily doses of HTLE (3 mg/kg) over a 15-day period, evaluating its safety profile, pharmacokinetics, impact on body weight, hepatic fat content, expression of key enzymes involved in lipogenesis/fatty acid oxidation, and antioxidant capacity. HTLE decreased the body weight and food intake in both rat genotypes. Biochemical analysis demonstrated a favorable safety profile for HTLE along with decreased concentrations of urea, total cholesterol, and aspartate aminotransferase AST transaminases in plasma. Notably, HTLE exhibited potent antisteatotic effects in obese rats, evidenced by a decrease in liver fat content and downregulation of lipogenesis-related enzymes, alongside increased expression of proteins controlling lipid oxidation. Moreover, HTLE successfully counteracted the redox imbalance associated with MAFLD in obese rats, attenuating lipid peroxidation and replenishing both glutathione levels and the overall antioxidant. Our findings highlight the effectiveness of triple-action strategies in managing MAFLD effectively. Based on our results in the Zucker rat model, HTLE emerges as a promising candidate with triple functionality as an anorexigenic, antisteatotic, and antioxidant agent, offering potential relief from MAFLD symptoms associated with obesity while exhibiting minimal side effects. In conclusion, our study positions HTLE as a highly promising compound for therapeutic intervention in MAFLD treatment, warranting further exploration in clinical trials.

Endovascular Versus Medical Management in Distal Medium Vessel Occlusion Stroke: The DUSK Study.

BACKGROUND: Endovascular treatment (EVT) is part of the usual care for proximal vessel occlusion strokes. However, the safety and effectiveness of EVT for distal medium vessel occlusions remain unclear. We sought to compare the clinical outcomes of EVT to medical management (MM) for isolated distal medium vessel occlusions. METHODS: This is a retrospective analysis of prospectively collected data from seven comprehensive stroke centers. Patients were included if they had isolated distal medium vessel occlusion strokes due to middle cerebral artery M3/M4, anterior cerebral artery A2/A3, or posterior cerebral artery P1/P2 segments. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included 90-day good (mRS score, 0-2) and excellent (mRS score, 0-1) outcomes. Safety measures included symptomatic intracranial hemorrhage and 90-day mortality. RESULTS: A total of 321 patients were included in the analysis (EVT, 179; MM, 142; 40.8% treated with intravenous thrombolysis). In the inverse probability of treatment weighting model, there were no significant differences between EVT and MM in terms of the overall degree of disability (mRS ordinal shift; adjusted odds ratio [aOR], 1.25 [95% CI, 0.95-1.64]; P=0.110), rates of good (mRS score, 0-2; aOR, 1.32 [95% CI, 0.97-1.80]; P=0.075) and excellent (aOR, 1.32 [95% CI, 0.94-1.85]; P=0.098) outcomes, or mortality (aOR, 1.20 [95% CI, 0.78-1.85]; P=0.395) at 90 days. The multivariable regression model showed similar findings. Moreover, there was no difference between EVT and MM in rates of symptomatic intracranial hemorrhage in the multivariable regression model (aOR, 0.57 [95% CI, 0.21-1.58]; P=0.277), but the inverse probability of treatment weighting model showed a lower likelihood of symptomatic intracranial hemorrhage (aOR, 0.46 [95% CI, 0.24-0.85]; P=0.013) in the EVT group. CONCLUSIONS: This multicenter study failed to demonstrate any significant outcome differences among patients with isolated distal medium vessel occlusions treated with EVT versus MM. These findings reinforce clinical equipoise. Randomized clinical trials are ongoing and will provide more definite evidence.

Intraventricular Pilocytic Astrocytoma in Adults: A 25-year Single-Center Case Series and Systematic Review of the Literature.

BACKGROUND: Pilocytic astrocytomas (PA) are the most common gliomas in children/adolescents but are less common and poorly studied in adults. Here, we describe the clinical presentation, surgical management, and outcomes of surgically treated adult patients with intraventricular (IV) PA and review the literature. METHODS: Consecutive adult patients treated for IV brain tumors at a tertiary academic center over 25 years (1997-2023) were identified. Clinical data were reviewed retrospectively for adult IV PA patients. A systematic literature review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. RESULTS: Eight patients with IV PA were included. Median age was 25 years (range, 18-69 years), and 4 (50%) were female. The most common tumor location was the lateral ventricle (5, 63%), followed by the fourth ventricle (3, 37%). Subtotal and near total resection were the most common surgical outcomes (6 patients, 75%), followed by gross total resection in 2 (25%). Progression or recurrence occurred in 3 patients (37%), requiring repeat resection in 2 patients. The 5-year overall survival and progression-free survival were 67% and 40%, respectively. In addition, 42 cases were identified in the literature. CONCLUSIONS: PAs in adults are rare and an IV location is even more uncommon. The findings demonstrate the challenges in caring for these patients, with overall- and progression-free survival outcomes being poorer than the general adult PA population. Findings support the employment of surgical techniques and approaches that favor gross total resection when possible. Further studies are needed to better characterize this unique presentation.

Sex-based differences in growth-related IGF1 signaling in response to PAPP-A2 deficiency: comparative effects of rhGH, rhIGF1 and rhPAPP-A2 treatments.

BACKGROUND: Children with pregnancy-associated plasma protein-A2 (PAPP-A2) mutations resulting in low levels of bioactive insulin-like growth factor-1 (IGF1) and progressive postnatal growth retardation have improved growth velocity and height following recombinant human (rh)IGF1 treatment. The present study aimed to evaluate whether Pappa2 deficiency and pharmacological manipulation of GH/IGF1 system are associated with sex-specific differences in growth-related signaling pathways. METHODS: Plasma, hypothalamus, pituitary gland and liver of Pappa2ko/ko mice of both sexes, showing reduced skeletal growth, and liver of these mice treated with rhGH, rhIGF1 and rhPAPP-A2 from postnatal day (PND) 5 to PND35 were analyzed. RESULTS: Reduced body and femur length of Pappa2ko/ko mice was associated with increases in: (1) components of IGF1 ternary complexes (IGF1, IGFBP5/Igfbp5, Igfbp3, Igfals) in plasma, hypothalamus and/or liver; and (2) key signaling regulators (phosphorylated PI3K, AKT, mTOR, GSK3ß, ERK1/2 and AMPKα) in hypothalamus, pituitary gland and/or liver, with Pappa2ko/ko females having a more prominent effect. Compared to rhGH and rhIGF1, rhPAPP-A2 specifically induced: (1) increased body and femur length, and reduced plasma total IGF1 and IGFBP5 concentrations in Pappa2ko/ko females; and (2) increased Igf1 and Igf1r levels and decreased Ghr, Igfbp3 and Igfals levels in the liver of Pappa2ko/ko females. These changes were accompanied by lower phospho-STAT5, phospho-AKT and phospho-ERK2 levels and higher phospho-AMPK levels in the liver of Pappa2ko/ko females. CONCLUSIONS: Sex-specific differences in IGF1 system and signaling pathways are associated with Pappa2 deficiency, pointing to rhPAPP-A2 as a promising drug to alleviate postnatal growth retardation underlying low IGF1 bioavailability in a female-specific manner.

Understanding the physiological role of pregnancy-associated plasma protein-A2 (PAPP-A2), a proteinase involved in the insulin-like growth factor-1 (IGF1) availability to regulate growth, could provide insight into new treatments for patients with short stature and skeletal abnormalities. Although progressive postnatal growth retardation in patients with PAPP-A2 mutations can differ between males and females, we do not know the underlying differences in IGF1 system and signaling, and their response to treatment that contribute to growth improvement. The present study examines whether Pappa2 deficiency and pharmacological administration of rhGH, rhIGF1 and rhPAPP-A2 are associated with sex-specific differences in IGF1 ternary complexes and IGF1 signaling pathways. Reduced body and femur length of Pappa2-deficient mice was associated with sex- and tissue-specific alteration of IGF ternary/binary complexes and IGF1 signaling pathways. rhPAPP-A2 treatment induced female-specific increase in body and femur length and reduction in IGF ternary/binary complexes through STAT5-AKT-ERK2-AMPK signaling pathways in liver. The involvement of PAPP-A2 in sex-based growth physiology supports the use of promising drugs to alleviate postnatal growth retardation underlying low IGF1 bioavailability in a female-specific manner.

Safety and effectiveness assessment of the surpass evolve (SEASE): a post-market international multicenter study.

BACKGROUND: Flow diverters are the first-line treatment for specific intracranial aneurysms (iA). Surpass Evolve (SE) is a new-generation 64-wire flow diverter with a high braid angle. Current literature on the SE is limited. We aimed to report the first international real-world experience evaluating the safety and effectiveness of the SE. METHODS: The Safety and Effectiveness Assessment of the Surpass Evolve (SEASE) was a multicenter retrospective international post-marketing cohort study including consecutive patients treated with SE for iAs between 2020 and 2022. Demographic, clinical, and angiographic data were collected. Primary effectiveness was independent core lab adjudicated complete occlusion rates (Raymond-Roy Class 1) at last follow-up. Primary safety were major ischemic/hemorrhagic events and mortality. RESULTS: In total, 305 patients with 332 aneurysms underwent SE implantation. The patients had a median age of 59 [50-67] years, and 256 (83.9%) were female. The baseline modified Rankin scale score was 0-2 in 291 patients (96.7%). Most aneurysms were unruptured (285, 93.4%) and saccular (309, 93.1%). Previous treatment was present in 76 (22.9%) patients. The median aneurysm size was 5.1 [3.4-9.0] mm, and the median neck width was 3.6 [2.7-5.1] mm. Most aneurysms were in the internal carotid artery C6 ophthalmic segment (126, 38.0%), followed by the communicating segment (58, 17.5%). At median 10.2 [6.4-12.9] months follow-up, 233 (73.0%) aneurysms achieved complete occlusion. After adjusting for confounders, complete occlusion remained consistent. Major stroke and procedure-related mortality were reported in 6 (2%) and 2 (0.7%) cases, respectively. CONCLUSION: These results demonstrate that SE has a consistently high effectiveness and favorable safety for the treatment of iAs.

Cellular Immunity of SARS-CoV-2 in the Borriana COVID-19 Cohort: A Nested Case-Control Study.

Our goal was to determine the cellular immune response (CIR) in a sample of the Borriana COVID-19 cohort (Spain) to identify associated factors and their relationship with infection, reinfection and sequelae. We conducted a nested case-control study using a randomly selected sample of 225 individuals aged 18 and older, including 36 individuals naïve to the SARS-CoV-2 infection and 189 infected patients. We employed flow-cytometry-based immunoassays for intracellular cytokine staining, using Wuhan and BA.2 antigens, and chemiluminescence microparticle immunoassay to detect SARS-CoV-2 antibodies. Logistic regression models were applied. A total of 215 (95.6%) participants exhibited T-cell response (TCR) to at least one antigen. Positive responses of CD4+ and CD8+ T cells were 89.8% and 85.3%, respectively. No difference in CIR was found between naïve and infected patients. Patients who experienced sequelae exhibited a higher CIR than those without. A positive correlation was observed between TCR and anti-spike IgG levels. Factors positively associated with the TCR included blood group A, number of SARS-CoV-2 vaccine doses received, and anti-N IgM; factors inversely related were the time elapsed since the last vaccine dose or infection, and blood group B. These findings contribute valuable insights into the nuanced immune landscape shaped by SARS-CoV-2 infection and vaccination.

Dental color measurement to estimate age in adults: a systematic review and meta-analysis.

Age estimation is a major challenge in anthropology and forensic odontology laboratories, as well as in judicial settings, as one of the tools used in human identification. The aim of this study was to evaluate the usefulness of age estimation methods based on the accurate measurement of tooth color changes. A systematic review was carried out following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and in compliance with Cochrane criteria recommendations (PROSPERO registration number CRD 42022343371). An electronic search was performed in the following databases: Pubmed, Web of Science, Medline, Current Contents Connect, SciELO, KCI-Korean Journal Database, Derwent Innovations Index and Russian Citation Index. The search strategy yielded a total of 18 articles. A randomized meta-analysis model of the results for the CIE L*a*b* color variables stratified by age (less than 30 years, 30-60 years, 60 years and older) was performed with 9 of the 18 studies included in this systematic review. According to our results, sex and location of color measurement are the most influential factors in color estimation. All studies were carried out in healthy anterior teeth by spectrophotometry as the most commonly used method for color measurement, with CIE L*a*b* being the most commonly analyzed parameters. Studies based on age as a dependent variable showed R2 values between 0.28 and 0.56, being higher in ex vivo teeth. Studies based on age as an independent variable showed R2 values ranging from 0.10 to 0.48. The random model showed high heterogeneity for the L*, a* and b* parameters in all age groups, which is explained by discrepancies in age range and non-standardized conditions for color measurement. This systematic review highlights the need to protocolize age estimation studies that measure tooth color, in order to apply this method in different forensic settings.

Anesthetic management for large vessel occlusion acute ischemic stroke with tandem lesions.

BACKGROUND: Endovascular therapy (EVT) stands as an established and effective intervention for acute ischemic stroke in patients harboring tandem lesions (TLs). However, the optimal anesthetic strategy for EVT in TL patients remains unclear. This study aims to evaluate the impact of distinct anesthetic techniques on outcomes in acute ischemic stroke patients presenting with TLs. METHODS: Patient-level data, encompassing cases from 16 diverse centers, were aggregated for individuals with anterior circulation TLs treated between January 2015 and December 2020. A stratification based on anesthetic technique was conducted to distinguish between general anesthesia (GA) and procedural sedation (PS). Multivariable logistic regression models were built to discern the association between anesthetic approach and outcomes, including the favorable functional outcome defined as 90-day modified Rankin Score (mRS) of 0-2, ordinal shift in mRS, symptomatic intracranial hemorrhage (sICH), any hemorrhage, successful recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) score ≥2b), excellent recanalization (mTICI 3), first pass effect (FPE), early neurological improvement (ENI), door-to-groin and recanalization times, intrahospital mortality, and 90-day mortality. RESULTS: Among 691 patients from 16 centers, 595 patients (GA 38.7%, PS 61.3%) were included in the final analysis. There were no significant differences noted in the door-to-groin time (80 (46-117.5) mins vs 54 (21-100), P=0.607) and groin to recanalization time (59 (39.5-85.5) mins vs 54 (38-81), P=0.836) among the groups. The odds of a favorable functional outcome (36.6% vs 52.6%; adjusted OR (aOR) 0.56, 95% CI 0.38 to 0.84, P=0.005) and a favorable shift in the 90-day mRS (aOR 0.71, 95% CI 0.51 to 0.99, P=0.041) were lower in the GA group. No differences were noted for sICH (3.9% vs 4.7%, P=0.38), successful recanalization (89.1% vs 86.5%, P=0.13), excellent recanalization (48.5% vs 50.3%, P=0.462), FPE (53.6% vs 63.4%, P=0.05), ENI (38.9% vs 38.8%, P=0.138), and 90-day mortality (20.3% vs 16.3%, P=0.525). An interaction was noted for favorable functional outcome between the type of anesthesia and the baseline Alberta Stroke Program Early CT Score (ASPECTS) (P=0.033), degree of internal carotid artery (ICA) stenosis (P<0.001), and ICA stenting (P<0.001), and intraparenchymal hematoma between the type of anesthesia and intravenous thrombolysis (P=0.019). In a subgroup analysis, PS showed better functional outcomes in patients with age ≤70 years, National Institutes of Health Stroke Scale (NIHSS) score <15, and acute ICA stenting. CONCLUSIONS: Our findings suggest that the preference for PS not only aligns with comparable procedural safety but is also associated with superior functional outcomes. These results prompt a re-evaluation of current anesthesia practices in EVT, urging clinicians to consider patient-specific characteristics when determining the optimal anesthetic strategy for this patient population.

Plasma Concentrations of High Mobility Group Box 1 Proteins and Soluble Receptors for Advanced Glycation End-Products Are Relevant Biomarkers of Cognitive Impairment in Alcohol Use Disorder: A Pilot Study.

Alcohol use disorder (AUD) is a major component in the etiology of cognitive decline and dementia. Underlying mechanisms by which long-term alcohol abuse causes cognitive dysfunction include excessive oxidative stress and inflammation in the brain, activated by increased reactive oxygen/nitrogen species (ROS/RNS), advanced glycation end-products (AGEs) and high-mobility group box 1 protein (HMGB1). In a pilot study, we examine the potential clinical value of circulating biomarkers of oxidative stress including ROS/RNS, HMGB1, the soluble receptor for AGE (sRAGE), the brain biomarker of aging apolipoprotein D (ApoD), and the antioxidant regulator nuclear factor erythroid 2-related factor 2 (NRF2) as predictive indices for cognitive impairment (CI) in abstinent patients with AUD (n = 25) compared to patients with established Alzheimer's disease (AD, n = 26) and control subjects (n = 25). Plasma concentrations of sRAGE were evaluated with immunoblotting; ROS/RNS with a fluorometric kit; and HMGB1, ApoD, and NRF2 by ELISA. Abstinent AUD patients had higher sRAGE, ROS/RNS (p < 0.05), and ApoD (p < 0.01) concentrations, similar to those of AD patients, and lower NRF2 (p < 0.01) concentrations, compared to controls. These changes were remarkable in AUD patients with CI. HMGB1, and sRAGE correlated positively with duration of alcohol use (rho = 0.398, p = 0.022; rho = 0.404, p = 0.018), whereas sRAGE correlated negatively with periods of alcohol abstinence (rho = -0.340, p = 0.045). A predictive model including ROS/RNS, HMGB1, sRAGE, alcohol use duration, and alcohol abstinence periods was able to differentiate AUD patients with CI (92.3% of correct predictions, ROC-AUC= 0.90) from those without CI. In conclusion, we propose ROS/RNS, HMGB1, and sRAGE as stress biomarkers capable of predicting cognitive impairment in AUD patients.

Early and late basilar artery thrombectomy time window outcomes.

Importance: Stroke-to-recanalization time is a strong predictor of outcomes in anterior circulation large-vessel occlusion (LVO). The authors aimed to evaluate functional outcomes in early (<6 h) vs. late (6-24 h) time windows for thrombectomy-treated basilar artery occlusions. Methods: Patients were derived from the Posterior Circulation Ischemic Stroke Evaluation: Analyzing Radiographic and Intra-procedural Predictors of Mechanical Thrombectomy (PC-SEARCH) Registry and retrospectively analyzed early and late basilar artery thrombectomy time windows cohorts. Patients were dichotomized based on the last known well and correlated to 90-day functional outcomes (mRS 0-3). A multiple logistic regression analysis was performed. Results: A total of 405 patients were included in this study: 216 and 189 patients in the early and late time windows, respectively. Baseline demographic, stroke, radiographic, and intraprocedural characteristics were similar between the groups. A total of 99 (46%) and 79 (42%) patients in the early and late time windows, respectively, achieved favorable functional outcomes at 90 days (p = 0.41), and multiple logistic regression analysis did not reveal differences between cohorts (OR: 0.74; 95% CI: 0.46-1.19; p = 0.22). Symptomatic hemorrhage (7% vs. 5%; p = 0.69) and neurological complications (8% vs. 9%; p = 0.83) were similar between the groups; however, hospital complications were more common in the early time window cohort (22% vs. 13%; p = 0.01). Conclusion: The early and late thrombectomy time windows can achieve similar rates of 90-day favorable functional outcomes. However, timely thrombectomy influences the likelihood of achieving excellent functional outcomes (mRS ≤ 2) within the early time window.

Inhibition of Adult Neurogenesis in Male Mice after Repeated Exposure to Paracetamol Overdose.

Paracetamol, or acetaminophen (N-acetyl-para-aminophenol, APAP), is an analgesic and antipyretic drug that is commonly used worldwide, implicated in numerous intoxications due to overdose, and causes serious liver damage. APAP can cross the blood-brain barrier and affects brain function in numerous ways, including pain signals, temperature regulation, neuroimmune response, and emotional behavior; however, its effect on adult neurogenesis has not been thoroughly investigated. We analyze, in a mouse model of hepatotoxicity, the effect of APAP overdose (750 mg/kg/day) for 3 and 4 consecutive days and after the cessation of APAP administration for 6 and 15 days on cell proliferation and survival in two relevant neurogenic zones: the subgranular zone of the dentate gyrus and the hypothalamus. The involvement of liver damage (plasma transaminases), neuronal activity (c-Fos), and astroglia (glial fibrillar acidic protein, GFAP) were also evaluated. Our results indicated that repeated APAP overdoses are associated with the inhibition of adult neurogenesis in the context of elevated liver transaminase levels, neuronal hyperactivity, and astrogliosis. These effects were partially reversed after the cessation of APAP administration for 6 and 15 days. In conclusion, these results suggest that APAP overdose impairs adult neurogenesis in the hippocampus and hypothalamus, a fact that may contribute to the effects of APAP on brain function.

Predictors of outcome and symptomatic intracranial hemorrhage in acute basilar artery occlusions: Analysis of the PC-SEARCH thrombectomy registry.

INTRODUCTION: Recent randomized controlled trials demonstrated superiority of mechanical thrombectomy compared to medical therapy in acute basilar artery occlusions, however, little data is available to guide clinicians in functional prognosis and risk stratification. PATIENTS AND METHODS: Data from the retrospectively established PC-SEARCH Thrombectomy registry, which included patients with basilar artery occlusion from eight sites from January 2015 to December 2021, was interrogated. Outcomes were dichotomized into 90-day favorable (mRS ⩽ 3) and unfavorable (mRS > 3). Multivariate logistic regression analysis was performed with respect to the outcome groups and were adjusted for potential confounding baseline characteristics. RESULTS: Four-hundred-forty-four patients were included in this analysis. Mean age was 66 [SD 15], with 56% male, and comprised of 76% Caucasian. Patients presented with an initial median NIHSS of 18 and 199 patients (44.8%) achieved favorable 90-day functional outcomes. Independent predictors of favorable outcomes included younger age, pc-ASPECTS > 8 (OR 2.30 p < 0.001), and TICI ⩾ 2b (OR 7.56 p < 0.001). Unfavorable outcomes were associated with increasing number of passes (OR 1.29 p = 0.004) and sICH (OR 4.19 p = 0.015). IA-tPA was an independent risk factor for sICH (OR 7.15 p = 0.002) without improving favorable functional outcomes. CONCLUSION AND DISCUSSION: PC-ASPECTS > 8, successful recanalization (TICI ⩾ 2b), first-pass recanalization, and younger age are independent predictors of favorable 90-day functional outcome in thrombectomy treated patients with acute basilar artery occlusion. Conversely, sICH were independent predictors of unfavorable outcomes. IA-tPA and unsuccessful recanalization are independently associated with sICH.

Survival and neurological outcomes following management of intramedullary spinal metastasis patients: a case series with comprehensive review of the literature.

Intramedullary spinal cord metastasis (ISCM), though rare, represents a potentially debilitating manifestation of systemic cancer. With emerging advances in cancer care, ISCMs are increasingly being encountered in clinical practice. Herein, we describe one of the larger retrospective single institutional case series on ISCMs, analyze survival and treatment outcomes, and review the literature. All surgically evaluated ISCMs at our institution between 2005 and 2023 were retrospectively reviewed. Demographics, tumor features, treatment, and clinical outcome characteristics were collected. Neurological function was quantified via the Frankel grade and the McCormick score (MCS). The pre- and post-operative Karnofsky performance scores (KPS) were used to assess functional status. Descriptive statistics, univariate analysis, log-rank test, and the Kaplan-Meier survival analysis were performed. A total of 9 patients were included (median age 67 years (range, 26-71); 6 were male). Thoracic and cervical spinal segments were most affected (4 patients each). Six patients (75%) underwent surgical management (1 biopsy and 5 resections), and 3 cases underwent chemoradiation only. Post-operatively, 2 patients had an improvement in their neurological exam with one patient becoming ambulatory after surgery; three patients maintained their neurological exam, and 1 had a decline. There was no statistically significant difference in the pre- and post-operative MCS and median KPS scores in surgically treated patients. Median OS after ISCM diagnosis was 7 months. Absence of brain metastasis, tumor histology (renal and melanoma), cervical/thoracic location, and post-op KPS ≥ 70 showed a trend toward improved overall survival. The incidence of ISCM is increasing, and earlier diagnosis and treatment are considered key for the preservation of neurological function. When patient characteristics are favorable, surgical resection of ISCM can be considered in patients with rapidly progressive neurological deficits. Surgical treatment was not associated with an improvement in overall survival in patients with ISCMs.