Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke: The MARVEL Randomized Clinical Trial.

Importance: It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective: To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023. Interventions: Eligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures: The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results: Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance: Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability. Trial Registration: ChiCTR.org.cn Identifier: ChiCTR2100051729.

An actively stabilized, miniaturized epi-fluorescence widefield microscope for real-time observation in vivo.

Recent developments in real-time, in vivo micro-imaging have allowed for the visualization of tissue pathological changes, facilitating rapid diagnosis. However, miniaturization, magnification, the field of view, and in vivo image stabilization remain challenging factors to reconcile. A key issue for this technology is ensuring it is user friendly for surgeons, enabling them to use the device manually and obtain instantaneous information necessary for surgical decision-making. This descriptive study introduces a handheld, actively stabilized, miniaturized epi-fluorescence widefield microscope (MEW-M) for real-time observation in vivo with high resolution. The methodology of MEW-M system includes high resolution microscopy miniaturization technology, thousandfold shaking suppression (actively stabilized), ultra-photosensitivity, and tailored image signal processing cell image capture and processing technology, which support for the excellent real-time imaging performance of MEW-M system in brain, mammary, liver, lung, and kidney tissue imaging of rats in vivo. With a single-objective and high-frame-rate imaging, the MEW-M system facilitates roving image acquisition, enabling contiguous analysis of large tissue areas. RESEARCH HIGHLIGHTS: A handheld, actively stabilized MEW-M system was introduced. Excellent real-time, in vivo imaging with high resolution and active stabilization in brain, mammary, liver, lung, and kidney tissue of rats.

Endovascular Therapy for Basilar Artery Occlusion in Sudden Onset to Maximal Deficit Ischemic Events.

BACKGROUND: The presence of sudden onset to maximal deficit (SOTMD) in patients with acute basilar artery occlusion often results in more severe outcomes. However, the effect of endovascular therapy on SOTMD and whether the outcome is affected by onset-to-puncture time remain unclear. METHODS AND RESULTS: This retrospective analysis was conducted using data from the prospective BASILAR (Endovascular Treatment for Acute Basilar Artery Occlusion Study Registry). Consecutive patients with basilar artery occlusion receiving endovascular therapy were dichotomized into SOTMD and non-SOTMD cohorts. The primary outcomes included a favorable outcome (modified Rankin scale 0-3), recanalization, and mortality at 90 days. The outcomes of patients with SOTMD were analyzed using multivariable logistic regression. In the multivariate analysis, a favorable outcome was similar between the two cohorts (odds ratio [OR], 0.88 [95% CI, 0.58-1.34]; P=0.5), although the mortality of patients with SOTMD was higher than that of patients with non-SOTMD (OR, 1.67 [95% CI, 1.14-2.44]; P=0.008). The probability of mortality increased from 40.0% at 1 hour to 70.0% at 6 hours in the SOTMD cohort, and favorable outcomes of patients with non-SOTMD declined from 38.0% at 1 hour to 18.0% at 8 hours. CONCLUSIONS: No significant difference was observed in favorable outcomes between the SOTMD and non-SOTMD groups, although mortality was higher in the SOTMD cohort. The patients with SOTMD had a stronger time dependence for endovascular therapy in terms of mortality, while the time dependency regarding favorable outcome in the NSOTMD group was even higher. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1800014759.

Diversity of Rickettsiales bacteria in five species of ticks collected from Jinzhai County, Anhui Province, China in 2021-2022.

The order Rickettsiales in the class Alphaproteobacteria comprises vector-borne pathogens of both medical and veterinary importance. Ticks, as a group, are second only to mosquitoes as vectors of pathogens to humans, playing a critical role in the transmission of rickettsiosis. In the present study, 880 ticks collected from Jinzhai County, Lu'an City, Anhui Province, China in 2021-2022 were identified as belonging to five species from three genera. DNA extracted from individual ticks was examined using nested polymerase chain reaction targeting the 16S rRNA gene (rrs), and the gene fragments amplified were sequenced to detect and identify Rickettsiales bacteria in the ticks. For further identification, the rrs-positive tick samples were further amplified by PCR targeting the gltA and groEL gene and sequenced. As a result, 13 Rickettsiales species belonging to the genera Rickettsia, Anaplasma, and Ehrlichia were detected, including three tentative species of Ehrlichia. Our results reveal the extensive diversity of Rickettsiales bacteria in ticks from Jinzhai County, Anhui Province. There, emerging rickettsial species may be pathogenic and cause under-recognized diseases. Detection of several pathogens in ticks that are closely related to human diseases may indicate a potential risk of infection in humans. Therefore, additional studies to assess the potential public health risks of the Rickettsiales pathogens identified in the present study are warranted.

Molecular phenotypic linkage between N6-methyladenosine methylation and tumor immune microenvironment in hepatocellular carcinoma.

PURPOSE: The crucial role of N6-methyladenosine (m6A) methylation in anti-tumor immunity and immunotherapy has been broadly depicted. However, the molecular phenotypic linkages between m6A modification pattern and immunological ecosystem are expected to be disentangled in hepatocellular carcinoma (HCC), for immunotherapeutic unresponsiveness circumvention and combination with promising drug agents. METHODS: Modification patterns of m6A methylation were qualitatively dissected according to the large-scale HCC samples profiling. We then determined the immune phenotypic linkages by systematically evaluating their tumor microenvironment composition, immune/stromal-relevant signature, immune checkpoints correlation, and prognostic value. Individual quantification of m6A methylation pattern was achieved by m6Ascore construction, intensified by longitudinal single-cell analysis of immunotherapy cohort and validated by the transcriptomic profiles of our in-hospital GDPH-HCC cohort. Candidate therapeutic agents were also screened out. RESULTS: Three distinct m6A methylation patterns were determined in high accordance with inflamed-, excluded-, and desert-immunophenotype. To be precise, Immune-inflamed high-m6Ascore group was characterized by activated immunity with favorable prognosis. Stromal activation and absence of immune cell infiltration were observed in low-m6Ascore phenotype, linked to impaired outcome. Patients with low-m6Ascore demonstrated diminished responses and clinical benefits for cohorts receiving immunotherapy. The above credible linkage between m6A methylation pattern and tumor immune microenvironment was robustly validated in our GDPH-HCC cohort. Single-cell dynamic change of m6A methylation level in exhausted CD8 T cell and fibroblast was depicted in immunotherapy cohort fore and art. Derived from m6A methylation pattern, seven potential frontline drug agents were recognized as promising choice for high-m6Ascore patients. CONCLUSION: Our work bridged the credible linkage between epigenetics and anti-tumor immunity in HCC, unraveling m6A modification pattern as immunological indicator and predictor for immunotherapy. Individualized m6Ascore facilitated strategic choices to maximize therapy-responsive possibility.

First-pass effect in patients with acute basilar artery occlusions undergoing stent retriever thrombectomy.

OBJECTIVE: First-pass effect (FPE), defined as successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2b-3) with a single stent retriever attempt without salvage treatment, has not been fully identified in patients with acute basilar artery occlusion (BAO). The authors' aim was to assess the impact of FPE on efficacy and safety for patients with BAO. METHODS: The authors included data from the Acute Basilar Artery Occlusion Study (BASILAR) about patients who underwent mechanical thrombectomy within 24 hours after symptom onset and compared the clinical outcomes of patients who achieved FPE with those who did not. In addition, the authors further compared outcomes between patients with FPE and those with final successful reperfusion achieved with salvage treatment. The primary clinical outcome was favorable outcome (modified Rankin Scale score ≤ 3). RESULTS: Among 471 enrolled patients, FPE was achieved in 83 (17.6%) who underwent acute BAO thrombectomy. FPE was strongly associated with favorable outcome (adjusted OR 2.84, 95% CI 1.56-5.16, p = 0.001), lower rate of mortality (28.9% of FPE patients vs 48.2% of non-FPE patients, p = 0.001), and shorter median time from groin puncture to recanalization (65 minutes vs 110 minutes, p < 0.001). Occlusion site of the distal basilar artery, cardioembolism, and undetermined etiology were positive predictors of FPE, whereas baseline National Institutes of Health Stroke Scale score was a negative predictor. Compared with final successful reperfusion, FPE also contributed independently to favorable outcomes (adjusted OR 2.25, 95% CI 1.23-4.10, p = 0.008). CONCLUSIONS: FPE was associated with 90-day favorable outcome in patients with acute BAO who underwent stent retriever thrombectomy within 24 hours. Clinical trial registration no.: ChiCTR1800014759 (www.chictr.org.cn).

Locked-in syndrome responding to endovascular treatment.

BACKGROUND: Locked-in syndrome (LiS) is a rare and devastating condition in patients with acute basilar artery occlusion. However, the benefits of endovascular treatment (EVT) for LiS remain unclear. OBJECTIVE: To assess the outcomes associated with EVT and identify the factors associated with outcomes of LiS. METHODS: We used the data of the Endovascular Treatment for Acute Basilar Artery Occlusion Study Registry (BASILAR) from 47 tertiary stroke centers in China. The included patients had LiS and received EVT or standard medical treatment (SMT) alone. The primary outcome was improvement in the modified Rankin Scale (mRS) score at 90 days. RESULTS: Among the 120 patients with LiS, 92 (76.7%) received EVT and 28 (23.3%) received SMT. Compared with SMT, EVT was associated with improved mRS score (common OR (cOR)=2.68 (95% CI 1.16 to 6.20); p=0.02) and decreased mortality (aOR=0.35 (95% CI 0.13 to 0.90); p=0.03). Moreover, the benefit of EVT for LiS was sustained for at least 1 year (p=0.008). Higher baseline posterior circulation Alberta Stroke Prognosis Early CT Score (pc-ASPECTS, aOR=2.04 (95% CI 1.34 to 3.10); p<0.001) and absence of pneumonia (aOR=0.26 (95% CI 0.08 to 0.90); p=0.03) were significantly associated with favorable functional outcome at 90 days in patients who received EVT, while lower pc-ASPECTS (aOR=0.52 (95% CI 0.36 to 0.76); p<0.001) was associated with increased 90-day mortality. CONCLUSIONS: This study found that EVT was associated with favorable functional outcomes and decreased mortality among patients with LiS. Baseline pc-ASPECTS and pneumonia were independent predictors of outcomes.

Neutrophil-to-lymphocyte ratio predicts parenchymal hematoma after mechanical thrombectomy in basilar artery occlusion.

Background: parenchymal hematoma (PH) is a severe complication of endovascular treatment (EVT) for acute basilar artery occlusion (ABAO). This study aimed to evaluate the incidence and predictors of PH after EVT for ABAO. Methods: Using data from the Endovascular Treatment for Acute Basilar Artery Occlusion Study, we enrolled patients treated with mechanical thrombectomy from the BASILAR registry. PH was assessed in accordance with the Heidelberg Bleeding Classification. Logistic regression was used to identify predictors of PH. Results: A total of 639 patients were included. Forty-eight patients (7.5%) were diagnosed with PH within 48 h of EVT. Ninety-day mortality was higher in patients with PH compared with those without (81.3 vs. 42.8%, P < 0.001). Favorable neurological outcomes (modified Rankin scale score, 0-3) rates was lower in patients with PH compared with those without (6.3 vs. 34.5%, P < 0.001). With a multivariate analysis, hypertension [odds ratio (OR) = 2.30, 95% confidence interval (CI) 1.04-5.08], pre-treatment National Institutes of Health Stroke Score (NIHSS, >25; OR = 3.04, 95% CI 1.43-6.45), and Neutrophil-to-lymphocyte ratio (NLR, >10; OR = 1.88, 95% CI 1.02-3.48) were associated with PH after EVT. Conclusions: PH occurred at a rate of 7.5% after EVT in patients with ABAO. Hypertension, higher baseline NIHSS, and higher NLR value increase the risk of PH after EVT for ABAO.

Hyperdense Artery Sign and Clinical Outcomes After Endovascular Treatment in Acute Basilar Artery Occlusion.

Background: This study aimed to investigate the association between the hyperdense basilar artery sign (HBAS) on non-enhanced computed tomography (CT) and clinical outcomes in patients with acute basilar artery occlusion (BAO) who underwent endovascular treatment (EVT). Methods: Eligible patients who underwent EVT due to acute BAO between January 2014 and May 2019 were divided into two groups based on HBAS. HBAS was assessed by two neuroradiologists using five grades on nonenhanced CT. The primary outcome was a favorable functional outcome (defined as a modified Rankin Scale [mRS] of 0-3) at 90 days. Secondary outcomes included successful recanalization and mortality within 90 days. Results: Among 829 patients with BAO as assessed with CT angiography, magnetic resonance angiography, or digital subtraction angiography, 643 patients were treated with EVT. Of these, 51.32% (330/643) had HBAS. Patients with HBAS were older and had more severe neurological deficits and a higher frequency of atrial fibrillation than those without HBAS. There was no significant difference in favorable outcome (adjusted odds ratio [aOR]: 1.354, 95% confidence interval [CI]: 0.906-2.024; p = 0.14), successful recanalization (aOR: 0.926, 95% CI: 0.616--1.393; p = 0.71), and mortality (aOR: 1.193, 95% CI: 0.839-1.695; p = 0.33) between patients with or without HBAS. Subgroup analysis showed that the HBAS predicted a favorable outcome in patients aged <60 years (aOR: 2.574, 95% CI: 1.234-5.368; p = 0.01) and patients with vertebral artery-V4 segment occlusion (aOR: 3.738, 95% CI: 1.212-11.530; p = 0.02). In patients with HBAS, the baseline National Institutes of Health Stroke Scale (NIHSS) score, posterior circulation-Acute Stroke Prognosis Early Computed Tomography Score (pc-ASPECTS), and stent retriever were associated with successful recanalization. Conclusions: Our study did not find a significant association between HBAS and favorable outcomes and successful recanalization in patients with BAO who underwent EVT. Moreover, large prospective studies are warranted to further investigate this relationship.

Super-resolution algorithm based on Richardson-Lucy deconvolution for three-dimensional structured illumination microscopy.

Three-dimensional structured illumination microscopy (3D-SIM) is a wide-field super-resolution technique in fluorescent imaging that can double the resolution beyond its classical limit. We introduce, to the best of our knowledge, a new 3D reconstruction algorithm based on the Richardson-Lucy deconvolution. The 3D-SIM imaging principle and the reconstruction steps are demonstrated in detail. Microspheres and biological specimen are used to present the performance of this method. The background of the out-of-focus portion is effectively suppressed, and true optical sectioning and super-resolution can be achieved simultaneously. For the custom-built 3D-SIM and this reconstruction algorithm, the measured resolution was 99.5±5 nm laterally and 294±9 nm axially.