Association of elevated lipoprotein(a) levels with ischemic stroke in young patients - a systematic review and meta-analysis.

INTRODUCTION: Lipoprotein(a) [Lp(a)] is an established independent causal risk factor for cardiovascular disease and atherosclerosis. However, its association with young-onset ischemic stroke is not well-established. A systematic review and meta-analysis was performed to investigate the association of elevated Lp(a) with young ischemic stroke. METHODS: Four electronic databases: PubMed (MEDLINE), EMBASE, Scopus and Cochrane Library were systematically searched, profiling studies from inception till 6 Mar 2024. We included studies investigating the relationship between stratified Lp(a) levels and young ischemic stroke. We compared the odds of young stroke patients (age <65 years) having elevated Lp(a) compared to age-matched controls without stroke or transient ischemic attack. RESULTS: Five case-control studies comprising a total of 1345 patients were included; 57.7 % (776/1345) were females, with a mean age of 41.5 years. Among them, 22.5 % (264/1171) were smokers. Additionally, 16.8 % (197/1171) had hypertension, 5.9 % (69/1171) had diabetes, and 29.2 % (284/971) had hyperlipidemia. Young stroke patients were more likely to have high Lp(a) level than age-matched controls (OR 1.61, 95 %CI 1.24-2.10). Four studies defined a high Lp(a) level as ≥30mg/dL, whilst one study used a Lp(a) level of >23.2mg/dL as the cut-off. A sensitivity analysis excluding this study showed that young stroke patients were still more likely to have Lp(a) ≥30mg/dL than controls (OR 1.43, 95 %CI 1.08-1.88). CONCLUSION: Young stroke patients are more likely to have elevated Lp(a) compared to age-matched controls, suggesting an association between elevated Lp(a) and young stroke. Further research is warranted to evaluate the causal relationships between Lp(a) and young-onset ischemic stroke, as well as to conduct a cost-benefit analysis of Lp(a) screening in young adults as part of a primary prevention strategy.

Mechanical Thrombectomy Versus Intravenous Thrombolysis in Distal Medium Vessel Acute Ischemic Stroke: A Multinational Multicenter Propensity Score-Matched Study.

Background and Purpose: The management of acute ischemic stroke (AIS) due to distal medium vessel occlusion (DMVO) remains uncertain, particularly in comparing the effectiveness of intravenous thrombolysis (IVT) plus mechanical thrombectomy (MT) versus IVT alone. This study aimed to evaluate the safety and efficacy in DMVO patients treated with either MT-IVT or IVT alone. Methods: This multinational study analyzed data from 37 centers across North America, Asia, and Europe. Patients with AIS due to DMVO were included, with data collected from September 2017 to July 2023. The primary outcome was functional independence, with secondary outcomes including mortality and safety measures such as types of intracerebral hemorrhage. Results: The study involved 1,057 patients before matching, and 640 patients post-matching. Functional outcomes at 90 days showed no significant difference between groups in achieving good functional recovery (modified Rankin Scale 0-1 and 0-2), with adjusted odds ratios (OR) of 1.21 (95% confidence interval [CI] 0.81 to 1.79; P=0.35) and 1.00 (95% CI 0.66 to 1.51; P>0.99), respectively. Mortality rates at 90 days were similar between the two groups (OR 0.75, 95% CI 0.44 to 1.29; P=0.30). The incidence of symptomatic intracerebral hemorrhage was comparable, but any type of intracranial hemorrhage was significantly higher in the MT-IVT group (OR 0.43, 95% CI 0.29 to 0.63; P<0.001). Conclusion: The results of this study indicate that while MT-IVT and IVT alone show similar functional and mortality outcomes in DMVO patients, MT-IVT presents a higher risk of hemorrhagic complications, thus MT-IVT may not routinely offer additional benefits over IVT alone for all DMVO stroke patients. Further prospective randomized trials are needed to identify patient subgroups most likely to benefit from MT-IVT treatment in DMVO.

Ethnic Differences in the Safety and Efficacy of Tenecteplase Versus Alteplase for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Background and Purpose: Tenecteplase is a thrombolytic agent with pharmacological advantages over alteplase and has been shown to be noninferior to alteplase for acute ischemic stroke in randomized trials. However, evidence pertaining to the safety and efficacy of tenecteplase in patients from different ethnic groups is lacking. The aim of this systematic review and metaanalysis was to investigate ethnicity-specific differences in the safety and efficacy of tenecteplase versus alteplase in patients with acute ischemic stroke. Methods: Following an International Prospective Register of Systematic Reviews (PROSPERO)- registered protocol (CRD42023475038), three authors conducted a systematic review of the PubMed/MEDLINE, Embase, Cochrane Library, and CINAHL databases for articles comparing the use of tenecteplase with any thrombolytic agent in patients with acute ischemic stroke up to November 20, 2023. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Two independent authors extracted data onto a standardized data collection sheet. A pairwise meta-analysis was conducted in risk ratios (RR). Results: From 34 studies (59,601 participants), the rate of complete recanalization was significantly higher (P<0.01) in Asian (RR: 1.91, 95% confidence interval [CI]: 1.30 to 2.80) versus Caucasian patients (RR: 0.99, 95% CI: 0.87 to 1.14). However, Asian patients (RR: 1.18, 95% CI: 0.87 to 1.62) had significantly higher (P=0.01) rates of mortality compared with Caucasian patients (RR: 1.10, 95% CI: 1.00 to 1.22). Caucasian patients were also more likely to attain a modified Rankin Scale (mRS) score of 0 to 2 at follow-up (RR: 1.14, 95% CI, 1.10 to 1.19) compared with Asian (RR: 1.00, 95% CI, 0.95 to 1.05) patients. There was no significant difference in the rate of symptomatic intracranial hemorrhage (P=0.20) and any intracranial hemorrhage (P=0.83) between Asian and Caucasian patients. Conclusion: Tenecteplase was associated with significantly higher rates of complete recanalization in Asian patients compared with Caucasian patients. However, tenecteplase was associated with higher rates of mortality and lower rates of mRS 0 to 2 in Asian patients compared with Caucasian patients. It may be beneficial to study the variations in response to tenecteplase among patients of different ethnic groups in large prospective cohort studies.

The effect of frailty on mortality and functional outcomes in spontaneous intracerebral haemorrhage.

INTRODUCTION: Limited data in patients with spontaneous intracerebral haemorrhage (SICH) showed that frailty was associated with mortality; however, there was insufficient data on functional outcomes. This study aimed to investigate the effect of frailty on overall mortality and 90-day functional outcomes in SICH. MATERIALS AND METHODS: We conducted a retrospective study of 1223 patients diagnosed with SICH from January 2014 to December 2020. Frailty was defined as a clinical frailty scale (CFS) score of 4-9. Binary cut-offs were defined using receiver operating curve analysis. 90-day poor functional outcomes (PFO) were defined as modified Rankin Scale (mRS) ≥3, and utility-weighted mRS (UW-mRS) were based on previous validated studies respectively. Regression analyses were conducted to investigate the association between frailty and outcomes. Confounders adjusted for included demographics, cardiovascular risk factors and haematoma characteristics. RESULTS: 1091 patients met the inclusion criterion. 167 (15.3 %) had 30-day mortality and 730 (66.9 %) had 90-day PFO. Frailty was significantly associated with lower overall survival (HR: 1.54; 95 % CI: 1.11-2.14, p=0.010), 90-day PFO (OR: 1.90; 95 % CI: 1.32-2.74; p<0.001) and poorer UW-mRS (ß: -0.06; 95 % CI: (-0.08 to -0.04); p<0.001) even after adjusting for confounders. CONCLUSIONS: Frailty was significantly associated with greater mortality and PFO after incident SICH, even after adjusting for a priori confounders. Frail male individuals may be predisposed to poorer outcomes from higher prevalence of cortical atrophy. The use of CFS in younger individuals may aid management by predicting outcomes after incident SICH. Identifying frail individuals with incident SICH could aid in decision-making and the surgical management of SICH.

Predictive value of follow-up infarct volume on functional outcomes in middle cerebral artery M2 segment vessel occlusion stroke treated with mechanical thrombectomy.

BACKGROUND: Medium vessel occlusion (MeVO) strokes, particularly affecting the M2 segment of the middle cerebral artery, represent a critical proportion of acute ischemic strokes, posing significant challenges in management and outcome prediction. The efficacy of mechanical thrombectomy (MT) in MeVO stroke may warrant reliable predictors of functional outcomes. This study aimed to investigate the prognostic value of follow-up infarct volume (FIV) for predicting 90-day functional outcomes in MeVO stroke patients undergoing MT. METHODS: This multicenter, retrospective cohort study analyzed data from the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry, covering patients with acute ischemic stroke due to M2 segment occlusion treated with MT. We examined the relationship between 90-day functional outcomes, measured by the modified Rankin Scale (mRS), and follow-up infarct volume (FIV), assessed through CT or MRI within 12-36 h post-MT. RESULTS: Among 130 participants, specific FIV thresholds were identified with high specificity and sensitivity for predicting outcomes. A FIV ⩽5 ml was highly specific for predicting favorable and excellent outcomes. The optimal cut-off for both prognostications was identified at ⩽15 ml by the Youden Index, with significant reductions in the likelihood of favorable outcomes observed above a 40 ml threshold. Receiver Operator Curve (ROC) analyses confirmed FIV as a superior predictor of functional outcomes compared to traditional recanalization scores, such as final modified thrombolysis in cerebral infarction score (mTICI). Multivariable analysis further highlighted the inverse relationship between FIV and positive functional outcomes. CONCLUSIONS: FIV within 36 h post-MT serves as a potent predictor of 90-day functional outcomes in patients with M2 segment MeVO strokes. Establishing FIV thresholds may aid in the prognostication of stroke outcomes, suggesting a role for FIV in guiding post intervention treatment decisions and informing clinical practice. Future research should focus on validating these findings across diverse patient populations and exploring the integration of FIV measurements with other clinical and imaging markers to enhance outcome prediction accuracy.

Assessment of Left Atrial Fibrosis by Cardiac Magnetic Resonance Imaging in Ischemic Stroke Patients Without Atrial Fibrillation: A Systematic Review and Meta-Analysis.

BACKGROUND: Left atrial (LA) fibrosis is a marker of atrial cardiomyopathy and has been reported to be associated with both atrial fibrillation and ischemic stroke. Elucidating this relationship is clinically important as LA fibrosis could serve as a surrogate biomarker of LA cardiomyopathy. The objective of this study is to investigate the association of LA fibrosis and embolic stroke of undetermined source (ESUS) using cardiac magnetic resonance imaging. METHODS AND RESULTS: Following an International Prospective Register of Systematic Reviews-registered protocol, 3 blinded reviewers performed a systematic review for studies that quantified the degree of LA fibrosis in patients with ESUS as compared with healthy patients from inception to February 2024. A meta-analysis was conducted in the mean difference. From 7 studies (705 patients), there was a significantly higher degree of LA fibrosis in patients with ESUS compared with healthy controls (MD, 5.71% [95% CI, 3.55%-7.87%], P<0.01). The degree of LA fibrosis was significantly higher in patients with atrial fibrillation than healthy controls (MD, 8.22% [95% CI, 5.62%-10.83%], P<0.01). A similar degree of LA fibrosis was observed in patients with ESUS compared with patients with atrial fibrillation (MD, -0.92% [95% CI, -2.29% to 0.44%], P=0.35). CONCLUSIONS: A significantly higher degree of LA fibrosis was found in patients with ESUS as compared with healthy controls. This suggests that LA fibrosis may play a significant role in the pathogenesis of ESUS. Further research is warranted to investigate LA fibrosis as a surrogate biomarker of atrial cardiomyopathy and recurrent stroke risk in patients with ESUS.

Clinical phenotypes and outcomes of patients with left ventricular thrombus: an unsupervised cluster analysis.

BACKGROUND: Left ventricular thrombus (LVT) can develop in a diverse group of patients with various underlying causes, resulting in divergent natural histories and trajectories with treatment. Our aim was to use cluster analysis to identify unique clinical profiles among patients with LVT and then compare their clinical characteristics, treatment strategies, and outcomes. METHODS: We conducted a retrospective study involving 472 patients with LVT whose data were extracted from a tertiary center's echocardiography database, from March 2011 to January 2021. We used the TwoStep cluster analysis method, examining 19 variables. RESULTS: Our analysis of the 472 patients with LVT revealed two distinct patient clusters. Cluster 1, comprising 247 individuals (52.3%), was characterized by younger patients with a lower incidence of traditional cardiovascular risk factors and relatively fewer comorbidities compared with Cluster 2. Most patients had LVT attributed to an underlying ischemic condition, with a larger proportion being due to post-acute myocardial infarction in Cluster 1 (68.8%), and due to ischemic cardiomyopathy in Cluster 2 (57.8%). Notably, patients in Cluster 2 exhibited a reduced likelihood of LVT resolution (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.44-0.77, p < 0.001) and a higher risk of all-cause mortality (HR 2.27, 95% CI 1.43-3.60, p = 0.001). These associations persisted even after adjusting for variables such as anticoagulation treatment, the presence of left ventricular aneurysms, and specific LVT characteristics such as mobility, protrusion, and size. CONCLUSION: Through TwoStep cluster analysis, we identified two distinct clinical phenotypes among patients with LVT, each distinguished by unique baseline clinical attributes and varying prognoses.

Simultaneous removal of endotoxins, inflammatory mediators and uremic toxins in ICU patients with septic shock: a retrospective cohort study.

Sepsis, one of the leading causes of death, is still lacking specific treatment. OXIRIS (BAXTER, Deerfield, IL, USA) is the first device allowing combined removal of endotoxins, inflammatory mediators and uremic toxins, alongside fluid balance control. Available data is very limited. This retrospective propensity score-matched cohort study of adult patients with septic shock aimed to evaluate septic shock duration and mortality in patients treated with either standard of care renal replacement therapy (RRT) or RRT with combined hemoadsorption, who were admitted to the interdisciplinary surgical intensive care unit at Heidelberg University Hospital during the years 2018 through 2021. Main outcomes were duration of shock, thirty-day mortality and plasma interleukin-6 levels before and after initiation of hemoadsorption. Included were 117 patients (female, 33%; male 67%); median age: 67 (16) years. After matching: 42 patients (female, 33%; male, 67%); mean age: 59.1 ± 13.8 years. There was no statistically significant difference in septic shock duration (p = 0.94; hazard ratio (HR) 0.97 (95% CI, 0.48-1.97)). Thirty-day survival analysis showed a non-statistically significant survival difference. (p = 0.063; HR 0.43 (95% CI, 0.17-1.09)). A post-hoc 90-day survival analysis revealed statistically significant longer survival and lower death hazard ratio in patients treated with RRT + HA (p = 0.037; HR = 0.42 (95% CI, 0.18-0.99). In conclusion, RRT with combined hemoadsorption of endotoxins, inflammatory mediators and uremic toxins is a modality worth further investigation.

Inflammation, Physical Activity, and Disease-Free Survival in Stage III Colon Cancer: CALGB/SWOG 80702 (Alliance).

BACKGROUND: Both inflammation and insufficient physical inactivity contribute to individual-level risk of disease recurrence and death in stage III colon cancer. The extent to which increased inflammatory risk can be offset by sufficient physical activity remains unknown. METHODS: This cohort study was nested within the CALGB/SWOG 80702 (Alliance) randomized trial. Inflammatory burden was quantified by high-sensitivity C-reactive protein, interleukin-6, and soluble tumor necrosis factor-α receptor 2 after recovery from tumor resection. Physical activity was measured during and after postoperative chemotherapy. The primary endpoint was disease-free survival. RESULTS: The 3-year disease-free survival rate was 88.4% among patients with low inflammation and sufficient physical activity (referent group for all comparisons), 84.9% with low inflammation and insufficient physical activity [absolute risk difference (RD): -3.5%, 95% Confidence Interval (CI): -11.3, 4.3; P = .38], 78.0% with intermediate inflammation and insufficient physical activity (RD: -10.4%, 95% CI: -17.4, -3.3; P = .007), and 79.7% with high inflammation and insufficient physical activity (RD: -8.7%, 95% CI: -15.7, -1.6; P = .022). In contrast, the 3-year disease-free survival rate was 87.3% among patients with intermediate inflammation and sufficient physical activity (RD: -1.1%, 95% CI: -7.5, 5.3; P = .74) and 84.4% with high inflammation and sufficient physical activity (RD: -4.0%, 95% CI: -12.3, 4.3; P = .34). CONCLUSION: In this observational study of stage III colon cancer patients, physical activity was associated with improved disease-free survival despite high inflammation. Patients with intermediate or high inflammation who were physically active had disease-free survival rates that were not statistically significantly different from those with low inflammation.

Arterial hypoperfusion as a negative predictive marker for primary hepatic malignancies treated with Y-90 glass microsphere transarterial radioembolization.

Background: Radioembolization with yttrium-90 (Y-90) is utilized to treat primary liver malignancies. The efficacy of this intra-arterial therapy in arterially hypoperfused tumors is not known. Methods: We reviewed data of patients with primary liver tumors treated with Y-90 prescription doses of at least 150 Gy. Baseline patient characteristics, treatment history, imaging-based tumor response assessments, and clinical outcome metrics were recorded. Tumors were classified as arterially hyperperfused versus hypoperfused on post-TARE Y-90 SPECT/CTs or pre-TARE hepatic perfusion SPECT/CTs. Perfusion status was correlated with tumor response assessments and clinical outcomes. Cox proportional hazards models were utilized to compare survival and progression-free survival. Inverse probability weighting was utilized to account for clinical factors and adjusted multivariable proportional hazards analyses to examine the relationship of quantitative perfusion and cancer outcomes. Results: Of 400 Y-90 treatments, 88 patients received a prescribed dose of at least 150 Gy and had pre- or post-treatment SPECT/CT images. 11 and 77 patients had arterially hypoperfused and hyperperfused lesions, respectively. On dedicated liver MRI or CT at 3 months after Y-90, the complete response rates were 5.6% and 16.5% in the hypoperfused and hyperperfused cohort, respectively (P = 0.60). When controlling for various clinical features, including tumor histology, patients with arterially hypoperfused tumors had significantly shorter progression-free survival (HR 1.87, 95% CI - 1.03 - 3.37, P = 0.039) and greater elsewhere liver (HR 3.36, 95% CI = 1.23 - 9.20, P = 0.019) and distant failure (HR 7.64 (2.71 - 21.54, P < 0.001). In inverse probability weighted analysis, patients with arterially hypoperfused tumors had worse overall survival (P = 0.032). In the quantitative analysis, lower levels of lesion perfusion were also associated with worse clinical outcomes, again controlling for tumor histology. Conclusion: Compared to arterially hyperperfused tumors, hypoperfused primary liver tumors treated with Y-90 may have worse clinical outcomes.

The Association of Obstructive Sleep Apnea with Urological Cancer Incidence and Mortality-A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVE: While obstructive sleep apnea (OSA) and urological cancer are both strongly associated with hypoxia, controversy exists regarding their association with each other. This study aims to summarize and synthesize evidence to clarify the association between OSA and urological cancer incidence and mortality. METHODS: According to a prespecified protocol, PubMed, Embase, Cochrane Library, and Scopus were searched from inception to November 16, 2023, for observational and randomized studies reporting the association of OSA with urological cancer incidence or mortality. We pooled maximally covariate-adjusted hazard ratios (HRs) using a random-effects inverse variance-weighted model. Two reviewers independently assessed the quality of evidence using the Newcastle-Ottawa Scale and the Grading of Recommendations, Assessment, Development and Evaluation framework. KEY FINDINGS AND LIMITATIONS: From 1814 records, we included 12 studies comprising 9 290 818 participants in total, of which nine studies were analyzed quantitatively. OSA patients had an increased risk of kidney (HR: 1.75, 95% confidence interval [CI]: 1.21-2.53) and bladder (HR: 1.76, 95% CI: 1.05-2.96) cancer. However, OSA was not associated with prostate cancer incidence (HR: 1.29, 95% CI: 0.82-2.04). We systematically reviewed evidence surrounding OSA and testicular cancer incidence and urological cancer mortality. CONCLUSIONS AND CLINICAL IMPLICATIONS: OSA may be associated with a higher risk of kidney and bladder cancer, but not prostate cancer. Future work may help clarify the possibility of a dose-response relationship between OSA and urological cancer, and the effect of OSA treatment on urological cancer incidence or progression. PATIENT SUMMARY: This research highlights a potential longitudinal association between OSA and kidney and bladder cancer, but not prostate cancer.

Assessment of Thrombectomy versus Combined Thrombolysis and Thrombectomy in Patients with Acute Ischemic Stroke and Medium Vessel Occlusion.

Background The combination of intravenous thrombolysis (IVT) with mechanical thrombectomy (MT) may have clinical benefits for patients with medium vessel occlusion. Purpose To examine whether MT combined with IVT is associated with different outcomes than MT alone in patients with acute ischemic stroke (AIS) and medium vessel occlusion. Materials and Methods This retrospective study included consecutive adult patients with AIS and medium vessel occlusion treated with MT or MT with IVT at 37 academic centers in North America, Asia, and Europe. Data were collected from September 2017 to July 2021. Propensity score matching was performed to reduce confounding. Univariable and multivariable logistic regression analyses were performed to test the association between the addition of IVT treatment and different functional and safety outcomes. Results After propensity score matching, 670 patients (median age, 75 years [IQR, 64-82 years]; 356 female) were included in the analysis; 335 underwent MT alone and 335 underwent MT with IVT. Median onset to puncture (350 vs 210 minutes, P < .001) and onset to recanalization (397 vs 273 minutes, P < .001) times were higher in the MT group than the MT with IVT group, respectively. In the univariable regression analysis, the addition of IVT was associated with higher odds of a modified Rankin Scale (mRS) score 0-2 (odds ratio [OR], 1.44; 95% CI: 1.06, 1.96; P = .019); however, this association was not observed in the multivariable analysis (OR, 1.37; 95% CI: 0.99, 1.89; P = .054). In the multivariable analysis, the addition of IVT also showed no evidence of an association with the odds of first-pass effect (OR, 1.27; 95% CI: 0.9, 1.79; P = .17), Thrombolysis in Cerebral Infarction grades 2b-3 (OR, 1.64; 95% CI: 0.99, 2.73; P = .055), mRS scores 0-1 (OR, 1.27; 95% CI: 0.91, 1.76; P = .16), mortality (OR, 0.78; 95% CI: 0.49, 1.24; P = .29), or intracranial hemorrhage (OR, 1.25; 95% CI: 0.88, 1.76; P = .21). Conclusion Adjunctive IVT may not provide benefit to MT in patients with AIS caused by distal and medium vessel occlusion. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Wojak in this issue.

Olfactory Impairment and Frailty: A Systematic Review and Meta-Analysis.

Importance: Olfactory impairment (OI) and frailty are prevalent conditions associated with aging, but studies investigating their association with each other have been discordant. Objective: To summarize current evidence surrounding the association between OI and frailty. Data Sources: PubMed, Embase, Cochrane Library, SCOPUS, and CINAHL from inception to November 28, 2023. Study Selection: This study included observational studies investigating the association between objectively or subjectively assessed OI and objectively evaluated frailty among adults. Data Extraction and Synthesis: Two independent authors extracted data into a structured template. Maximally adjusted estimates were pooled using a random-effects model, and statistical heterogeneity was evaluated using I2 values. Additional prespecified subgroup and sensitivity analyses were performed. This study used the Newcastle-Ottawa Scale for bias assessment and the Grading of Recommendations Assessment, Development and Evaluation framework for overall evidence quality evaluation. Main Outcomes and Measures: The primary outcome was the cross-sectional association between OI and frailty, for which the odds of frailty were compared between participants with and without OI. The secondary outcome was the cross-sectional association between frailty and OI, for which the odds of OI were compared between participants with and without frailty. Results: This study included 10 studies with 10 624 patients (52.9% female; mean [SD] age, 62.9 [9.6] years). The Newcastle-Ottawa Scale score of studies ranged from low to moderate. Grading of Recommendations Assessment, Development and Evaluation scores ranged from low to moderate. OI was associated with a 2.32-fold (odds ratio [OR], 2.32; 95% CI, 1.63-3.31; I2 = 0%) greater odds of frailty compared with individuals with healthy olfactory function. The odds of OI was progressively greater with categorical frailty status, with a 1.55-fold (OR, 1.55; 95% CI, 1.32-1.82; I2 = 0%), 2.28-fold (OR, 2.28; 95% CI, 1.96-2.65; I2 = 0%), and 4.67-fold (OR, 4.67; 95% CI, 2.77-7.86; I2 = 0%) increase in odds for individuals with prefrailty, frailty, and the most frailty, respectively, compared with robust individuals. The results demonstrated stability in subgroup analyses (geographical continent of study, objective vs subjective olfactory assessment) and sensitivity tests. Conclusions and Relevance: The results of this systematic review and meta-analysis suggest that there is an association between OI and frailty, with an increase in the odds of OI with worsening categorical frailty status among individuals with prefrailty, frailty, and the most frailty. OI may be a potential biomarker for frailty. Future studies could delve into whether OI may be a modifiable risk factor for frailty.

Multicenter evaluation of mechanical thrombectomy for distal medium vessel occlusions with National Institute of Health Stroke Scale Scores ≥ 6 and ≤ 6.

BACKGROUND: While mechanical thrombectomy is considered standard of care for large vessel occlusions, scientific evidence to support treatment for distal and medium vessel occlusions remains scarce. PURPOSE: To evaluate feasibility, safety, and outcomes in patients with low National Institute of Health Stroke Scale scores undergoing mechanical thrombectomy for treatment of distal medium vessel occlusions. MATERIALS AND METHODS: Retrospective data review and analysis of prospectively maintained databases at 41 academic centers in North America, Asia, and Europe between January 2017 and January 2022. Characteristics and outcomes were compared between groups with low stroke scale score (≤ 6) versus and higher stroke scale scores (> 6). Propensity score matching using the optimal pair matching method and 1:1 ratio was performed. RESULTS: Data were collected on a total of 1068 patients. After propensity score matching, there were a total of 676 patients included in the final analysis, with 338 patients in each group. High successful reperfusion rates were seen in both groups, 90.2% in ≤ 6 and 88.7% in the > 6 stroke scale groups. The frequency of excellent and good functional outcome was seen more common in low versus higher stroke scale score patients (64.5% and 81.1% versus 39.3% and 58.6%, respectively). The 90-day mortality rate observed in the ≤ 6 stroke scale group was 5.3% versus 13.3% in the > 6 stroke scale group. CONCLUSION: Mechanical thrombectomy in distal and medium vessel occlusions, specifically in patients with low stroke scale scores is feasible, though it may not necessarily improve outcomes over IVT.

Endovascular therapy versus best medical management in distal medium middle cerebral artery acute ischaemic stroke: a multinational multicentre propensity score-matched study.

BACKGROUND: The efficacy of endovascular treatment (EVT) in acute ischaemic stroke due to distal medium vessel occlusion (DMVO) remains uncertain. Our study aimed to evaluate the safety and efficacy of EVT compared with the best medical management (BMM) in DMVO. METHODS: In this prospectively collected, retrospectively reviewed, multicentre cohort study, we analysed data from the Multicentre Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy registry. Patients with acute ischaemic stroke due to DMVO in the M2, M3 and M4 segments who underwent EVT or received BMM were included. Primary outcome measures comprised 10 co-primary endpoints, including functional independence (mRS 0-2), excellent outcome (mRS 0-1), mortality (mRS 6) and haemorrhagic complications. Propensity score matching was employed to balance the cohorts. RESULTS: Among 2125 patients included in the primary analysis, 1713 received EVT and 412 received BMM. After propensity score matching, each group comprised 391 patients. At 90 days, no significant difference was observed in achieving mRS 0-2 between EVT and BMM (adjusted OR 1.00, 95% CI 0.67 to 1.50, p>0.99). However, EVT was associated with higher rates of symptomatic intracerebral haemorrhage (8.4% vs 3.0%, adjusted OR 3.56, 95% CI 1.69 to 7.48, p<0.001) and any intracranial haemorrhage (37% vs 19%, adjusted OR 2.61, 95% CI 1.81 to 3.78, p<0.001). Mortality rates were similar between groups (13% in both, adjusted OR 1.48, 95% CI 0.87 to 2.51, p=0.15). CONCLUSION: Our findings suggest that while EVT does not significantly improve functional outcomes compared with BMM in DMVO, it is associated with higher risks of haemorrhagic complications. These results support a cautious approach to the use of EVT in DMVO and highlight the need for further prospective randomised trials to refine treatment strategies.

Symptomatic intracerebral hemorrhage in proximal and distal medium middle cerebral artery occlusion patients treated with mechanical thrombectomy.

BACKGROUND: Acute ischemic stroke (AIS) caused by distal medium vessel occlusions (DMVOs) represents a significant proportion of overall stroke cases. While intravenous thrombolysis (IVT) has been a primary treatment, advancements in endovascular procedures have led to increased use of mechanical thrombectomy (MT) in DMVO stroke patients. However, symptomatic intracerebral hemorrhage (sICH) remains a critical complication of AIS, particularly after undergoing intervention. This study aims to identify factors associated with sICH in DMVO stroke patients undergoing MT. METHODS: This retrospective analysis utilized data from the Multicenter Analysis of Distal Medium Vessel Occlusions: Effect of Mechanical Thrombectomy (MAD-MT) registry, involving 37 centers across North America, Asia, and Europe. Middle cerebral artery (MCA) DMVO stroke patients were included. The primary outcome measured was sICH, as defined per the Heidelberg Bleeding Classification. Univariable and multivariable logistic regression were used to identify factors independently associated with sICH. RESULTS: Among 1708 DMVO stroke patients, 148 (8.7%) developed sICH. Factors associated with sICH in DMVO patients treated with MT included older age (adjusted odds ratio (aOR) 1.01, 95% confidence interval (95% CI) 1.00 to 1.03, P=0.048), distal occlusion site (M3, M4) compared with medium occlusions (M2) (aOR 1.71, 95% CI 1.07 to 2.74, P=0.026), prior use of antiplatelet drugs (aOR 2.06, 95% CI 1.41 to 2.99, P<0.001), lower Alberta Stroke Program Early CT Scores (ASPECTS) (aOR 0.75, 95% CI 0.66 to 0.84, P<0.001), higher preoperative blood glucose level (aOR 1.00, 95% CI 1.00 to 1.01, P=0.012), number of passes (aOR 1.27, 95% CI 1.15 to 1.39, P<0.001), and successful recanalization (Thrombolysis In Cerebral Infarction (TICI) 2b-3) (aOR 0.43, 95% CI 0.28 to 0.66, P<0.001). CONCLUSION: This study provides novel insight into factors associated with sICH in patients undergoing MT for DMVO, emphasizing the importance of age, distal occlusion site, prior use of antiplatelet drugs, lower ASPECTS, higher preoperative blood glucose level, and procedural factors such as the number of passes and successful recanalization. Pending confirmation, consideration of these factors may improve personalized treatment strategies.

Pre-treatment radiological factors associated with poor functional outcome in an Asian cohort of large vessel occlusion acute ischemic stroke patients undergoing mechanical thrombectomy.

Background and aims: Endovascular thrombectomy (EVT) is the current standard of care for large vessel occlusion (LVO) acute ischemic stroke (AIS); however, up to two-thirds of EVT patients have poor functional outcomes despite successful reperfusion. Many radiological markers have been studied as predictive biomarkers for patient outcomes in AIS. This study seeks to determine which clinico-radiological factors are associated with outcomes of interest to aid selection of patients for EVT for LVO AIS. Methods: A retrospective study of patients who underwent EVT from 2016 to 2020 was performed. Data on various radiological variables, such as anatomical parameters, clot characteristics, collateral status, and infarct size, were collected alongside traditional demographic and clinical variables. Univariate and multivariate analysis was performed for the primary outcomes of functional independence at 3 months post-stroke (modified Rankin Scale 0-2) and secondary outcomes of in-hospital mortality and symptomatic intracranial hemorrhage. Results: The study cohort comprised 325 consecutive patients with anterior circulation LVO AIS (54.5% male) with a median age of 68 years (interquartile range 57-76). The median NIHSS was 19. Age, hypertension, hyperlipidaemia, National Institutes of Health Stroke Scale (NIHSS), Alberta mCTA score, ASPECTS, clot length, thrombus HU and mTICI score and the angle between ICA and CCA were associated with functional outcomes at 3 months on univariate analysis. On multivariate analysis, age, Alberta mCTA collaterals and NIHSS were significantly associated with functional outcomes, while ASPECTS approached significance. Conclusion: Among the many proposed radiological markers for patients in the hyperacute setting undergoing EVT, the existing well-validated clinico-radiological measures remain strongly associated with functional status.

Pretreatment predictors of very poor clinical outcomes in medium vessel occlusion stroke patients treated with mechanical thrombectomy.

BACKGROUND: Acute ischemic stroke (AIS) from primary medium vessel occlusions (MeVO) is a prevalent condition associated with substantial morbidity and mortality. Despite the common use of mechanical thrombectomy (MT) in AIS, predictors of poor outcomes in MeVO remain poorly characterized. METHODS: In this prospectively collected, retrospectively reviewed, multicenter, multinational study, data from the MAD-MT (Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy) registry were analyzed. The study included 1568 patients from 37 academic centers across North America, Asia, and Europe, treated with MT, with or without intravenous tissue plasminogen activator (IVtPA), between September 2017 and July 2021. RESULTS: Among the 1568 patients, 347 (22.2%) experienced very poor outcomes (modified Rankin score (mRS), 5-6). Key predictors of poor outcomes were advanced age (odds ratio (OR): 1.03; 95% confidence interval (CI): 1.02 to 1.04; p < 0.001), higher baseline National Institutes of Health Stroke Scale (NIHSS) scores (OR: 1.07; 95% CI: 1.05 to 1.10; p < 0.001), pre-operative glucose levels (OR: 1.01; 95% CI: 1.00 to 1.02; p < 0.001), and a baseline mRS of 4 (OR: 2.69; 95% CI: 1.25 to 5.82; p = 0.011). The multivariable model demonstrated good predictive accuracy with an area under the receiver-operating characteristic (ROC) curve of 0.76. CONCLUSIONS: This study demonstrates that advanced age, higher NIHSS scores, elevated pre-stroke mRS, and pre-operative glucose levels significantly predict very poor outcomes in AIS-MeVO patients who received MT. These findings highlight the importance of a comprehensive risk assessment in primary MeVO patients for personalized treatment strategies. However, they also suggest a need for cautious patient selection for endovascular thrombectomy. Further prospective studies are needed to confirm these findings and explore targeted therapeutic interventions.

Incidence and Outcomes of Cardiocerebral Infarction: A Cohort Study of 2 National Population-Based Registries.

BACKGROUND: Cardiocerebral infarction (CCI), which is concomitant with acute myocardial infarction (AMI) and acute ischemic stroke (AIS), is a rare but severe presentation. However, there are few data on CCI, and the treatment options are uncertain. We investigated the characteristics and outcomes of CCI compared with AMI or AIS alone. METHODS: We performed a retrospective cohort study of 120 531 patients with AMI and AIS from the national stroke and AMI registries in Singapore. Patients were categorized into AMI only, AIS only, synchronous CCI (same-day), and metachronous CCI (within 1 week). The primary outcome was all-cause mortality, and the secondary outcome was cardiovascular mortality. The mortality risks were compared using Cox regression. Multivariable models were adjusted for baseline demographics, clinical variables, and treatment for AMI or AIS. RESULTS: Of 127 919 patients identified, 120 531 (94.2%) were included; 74 219 (61.6%) patients had AMI only, 44 721 (37.1%) had AIS only, 625 (0.5%) had synchronous CCI, and 966 (0.8%) had metachronous CCI. The mean age was 67.7 (SD, 14.0) years. Synchronous and metachronous CCI had a higher risk of 30-day mortality (synchronous: adjusted HR [aHR], 2.41 [95% CI, 1.77-3.28]; metachronous: aHR, 2.80 [95% CI, 2.11-3.73]) than AMI only and AIS only (synchronous: aHR, 2.90 [95% CI, 1.87-4.51]; metachronous: aHR, 4.36 [95% CI, 3.03-6.27]). The risk of cardiovascular mortality was higher in synchronous and metachronous CCI than AMI (synchronous: aHR, 3.03 [95% CI, 2.15-4.28]; metachronous: aHR, 3.41 [95% CI, 2.50-4.65]) or AIS only (synchronous: aHR, 2.58 [95% CI, 1.52-4.36]; metachronous: aHR, 4.52 [95% CI, 2.95-6.92]). In synchronous CCI, AMI was less likely to be managed with PCI and secondary prevention medications (P<0.001) compared with AMI only. CONCLUSIONS: Synchronous CCI occurred in 1 in 200 cases of AIS and AMI. Synchronous and metachronous CCI had higher mortality than AMI or AIS alone.