Brain imaging prior to thrombectomy in the late window of large vessel occlusion ischemic stroke: a systematic review and meta-analysis.

PURPOSE: Optimal imaging modalities to select patients for endovascular thrombectomy (EVT) in the late window of acute ischemic stroke due to large vessel occlusions (AIS-LVO) are not known. We conducted a systematic review comparing outcomes of patients selected by non-contrast computed tomography (NCCT)/CT angiography (CTA) vs. those selected by CT perfusion (CTP) or magnetic resonance imaging (MRI) for EVT in these patients. METHODS: We searched PUBMED, EMBASE, and the Cochrane Library from January 1, 2000, to July 15, 2023, to identify studies comparing outcomes of patients selected for EVT by NCCT/CTA vs. CTP or MRI in the late time window for AIS-LVO. Primary outcome was independence (mRS 0-2) at 90 days or discharge. Secondary outcomes were symptomatic intracranial hemorrhage (sICH) and mortality. We pooled data across studies based on an inverse variance method. RESULTS: Six cohort studies with 4208 patients were included. Pooled results showed no significant difference in the rate of independence at 90 days or discharge (RR 0.96, 95% CI 0.88-1.03) and sICH (RR 1.26, 0.85-1.86) between patients selected by NCCT/CTA vs. CTP or MRI for EVT in the late window of AIS-LVO. However, patients selected by NCCT/CTA vs. CTP or MRI for EVT were associated with a higher risk of mortality (RR 1.21, 1.06-1.39). CONCLUSION: For AIS-LVO in the late window, patients selected by NCCT/CTA compared with those selected by CTP or MRI for EVT might have a comparable rate of functional independence and sICH. Baseline NCCT/CTA may triage AIS-LVO in the late window.

Contact-Free Atrial Fibrillation Screening with Attention Network.

Atrial Fibrillation (AF) screening from face videos has become popular with the trend of telemedicine and telehealth in recent years. In this study, the largest facial image database for camera-based AF detection is proposed. There are 657 participants from two clinical sites and each of them is recorded for about 10 minutes of video data, which can be further processed as over 10,000 segments around 30 seconds, where the duration setting is referred to the guideline of AF diagnosis. It is also worth noting that, 2,979 segments are segment-wise labeled, that is, every rhythm is independently labeled with AF or not. Besides, all labels are confirmed by the cardiologist manually. Various environments, talking, facial expressions, and head movements are involved in data collection, which meets the situations in practical usage. Specific to camera-based AF screening, a novel CNN-based architecture equipped with an attention mechanism is proposed. It is capable of fusing heartbeat consistency, heart rate variability derived from remote photoplethysmography, and motion features simultaneously to reliable outputs. With the proposed model, the performance of intra-database evaluation comes up to 96.62% of sensitivity, 90.61% of specificity, and 0.96 of AUC. Furthermore, to check the capability of adaptation of the proposed method thoroughly, the cross-database evaluation is also conducted, and the performance also reaches about 90% on average with the AUCs being over 0.94 in both clinical sites.

Non-meningeal, non-pulmonary cryptococcosis with limited posterior uveitis in a kidney organ transplant recipient with antibody-mediated rejection: a case report.

BACKGROUND: Cryptococcosis is one of the most frequent fungal eye infections in patients with immunosuppression. Currently, treatment approaches for non-meningeal, non-pulmonary cryptococcosis are based on those used for cryptococcal meningitis or pneumonia. CASE PRESENTATION: We present a rare case of non-meningeal, non-pulmonary cryptococcosis with clinical manifestations limited to one eye of a cadaveric kidney transplant recipient with chronic-active antibody-mediated rejection. Typical manifestations, diagnosis, and treatments, including antifungal therapies, adjunctive therapies, and immunosuppression reduction, are discussed. After timely diagnosis and treatment, her visual acuity recovered to baseline without recurrence or sequelae of cryptococcosis. CONCLUSIONS: Clinicians should be aware of rare presentations of fungal infections, especially when a kidney transplant recipient with rejection has been treated with intensive immunosuppressants. Early diagnosis with individualized therapies may have a favorable prognosis.

The classification of stages of epiretinal membrane using convolutional neural network on optical coherence tomography image.

BACKGROUND AND OBJECTIVE: The gold standard for diagnosing epiretinal membranes is to observe the surface of the internal limiting membrane on optical coherence tomography images. The stages of the epiretinal membrane are used to decide the condition of the health of the membrane. The stages are not detected because some of them are similar. To accurately classify the stages, a deep-learning technology can be used to improve the classification accuracy. METHODS: A combinatorial fusion with multiple convolutional neural networks (CNN) algorithms are proposed to enhance the accuracy of a single image classification model. The proposed method was trained using a dataset of 1947 optical coherence tomography images diagnosed with the epiretinal membrane at the Taichung Veterans General Hospital in Taiwan. The images consisted of 4 stages; stages 1, 2, 3, and 4. RESULTS: The overall accuracy of the classification was 84%. The combination of five and six CNN models achieves the highest testing accuracy (85%) among other combinations, respectively. Any combination with a different number of CNN models outperforms any single CNN algorithm working alone. Meanwhile, the accuracy of the proposed method is better than ophthalmologists with years of clinical experience. CONCLUSIONS: We have developed an efficient epiretinal membrane classification method by using combinatorial fusion with CNN models on optical coherence tomography images. The proposed method can be used for screening purposes to facilitate ophthalmologists making the correct diagnoses in general medical practice.

Antimicrobial Peptide Mastoparan-AF Kills Multi-Antibiotic Resistant Escherichia coli O157:H7 via Multiple Membrane Disruption Patterns and Likely by Adopting 3-11 Amphipathic Helices to Favor Membrane Interaction.

We investigated the antimicrobial activity and membrane disruption modes of the antimicrobial peptide mastoparan-AF against hemolytic Escherichia coli O157:H7. Based on the physicochemical properties, mastoparan-AF may potentially adopt a 3-11 amphipathic helix-type structure, with five to seven nonpolar or hydrophobic amino acid residues forming the hydrophobic face. E. coli O157:H7 and two diarrheagenic E. coli veterinary clinical isolates, which are highly resistant to multiple antibiotics, are sensitive to mastoparan-AF, with minimum inhibitory and bactericidal concentrations (MIC and MBC) ranging from 16 to 32 µg mL-1 for E. coli O157:H7 and four to eight µg mL-1 for the latter two isolates. Mastoparan-AF treatment, which correlates proportionally with membrane permeabilization of the bacteria, may lead to abnormal dents, large perforations or full opening at apical ends (hollow tubes), vesicle budding, and membrane corrugation and invagination forming irregular pits or pores on E. coli O157:H7 surface. In addition, mRNAs of prepromastoparan-AF and prepromastoparan-B share a 5'-poly(A) leader sequence at the 5'-UTR known for the advantage in cap-independent translation. This is the first report about the 3-11 amphipathic helix structure of mastoparans to facilitate membrane interaction. Mastoparan-AF could potentially be employed to combat multiple antibiotic-resistant hemolytic E. coli O157:H7 and other pathogenic E. coli.

Effects of endovascular therapy for mild stroke due to proximal or M2 occlusions: meta-analysis.

OBJECTIVE: To conduct a meta-analysis to evaluate the effect of endovascular therapy (EVT) in mild acute ischemic stroke (AIS) due to proximal versus distal occlusions. METHODS: We searched PubMed, Embase, the Cochrane Library, and clinicaltrials.gov from January 2000 to September 2021 to identify studies comparing EVT versus best medical management (BMM) in AIS with National Institutes of Health Stroke Scale (NIHSS) scores ≤5 due to proximal internal carotid artery (ICA) or M1 versus distal M2 occlusions. We included studies that reported the number of patients with proximal or distal occlusions separately and reported the number of patients with freedom of disability (modified Rankin Scale (mRS) score 0-1) or functional independence (mRS score 0-2) at 90 days in proximal or M2 occlusions, respectively. OR with 95% CI was used. RESULTS: We identified six studies with 653 proximal ICA and M1 occlusion patients and 666 distal M2 occlusion patients. Pooled results showed EVT versus BMM was associated with a higher rate of being disability-free in patients with proximal occlusions (OR 1.58, 95% CI 1.09 to 2.30), but was associated with a lower rate of being disability-free in patients with M2 occlusions (OR 0.70, 95% CI 0.49 to 0.99). Effect of EVT in proximal versus distal occlusions was substantially different (P for interaction=0.002). A similar pattern was seen for functional independence (P for interaction=0.05). CONCLUSIONS: For patients with mild AIS, observational data suggest that EVT may be beneficial for proximal ICA or M1 but not for distal M2 occlusions. Randomized trials are needed to confirm these findings. PROSPERO REGISTRATION NUMBER: CRD42021281034.

Efficacy of endovascular therapy for basilar and vertebral artery occlusion: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The best management for acute basilar artery occlusion (BAO) has increasingly been clarified by recent randomized controlled trials (RCTs). We conducted a systematic review and meta-analysis of RCTs comparing endovascular therapy (EVT) vs best medical management (BMM). METHODS: We searched PubMed, Embase, the CENTRAL, and ClinicalTrials.gov from January 1, 2000, to November 20, 2022. We included RCTs comparing EVT vs BMM in BAO or bilateral vertebral artery occlusion (VAO). Primary outcome was ambulation (modified Rankin Scale score [mRS] 0-3) at 90 days. Secondary outcomes were independence (mRS 0-2) at 90 days, death by 90 days, and symptomatic intracranial hemorrhage (sICH). Risk ratio (RR) with 95% CI was used as a measure of the association of EVT vs BMM with outcomes. RESULTS: Final analyses included 4 RCTs with 988 patients with BAO or VAO. Pooled results showed that EVT vs BMM was associated with an increased rate of 90-day ambulation (RR 1.54, 95% CI 1.16-2.05), independence (RR 1.83, 1.08-3.08) and a reduced risk of mortality (RR 0.76, 0.65-0.89), but an increased risk of sICH (RR 7.48, 2.27-24.62) and the benefits might be confined to patients with BAO but not patients with VAO. EVT effect was modified by occlusion location with the basilar artery, with greatest benefit for proximal, intermediate benefit for middle, and least benefit for distal occlusions. CONCLUSION: EVT compared with BMM might be associated with an increased rate of ambulation, independence and survival but with an increased risk of sICH in patients with acute BAO.

Comparison of risk scores in predicting symptomatic intracerebral hemorrhage after endovascular thrombectomy.

BACKGROUND/PURPOSE: Several risk scores have been developed to predict symptomatic intracerebral hemorrhage (SICH) after acute reperfusion therapy for ischemic stroke. We compared the performance of established risk scores in predicting SICH after EVT under different SICH criteria. METHODS: A total of 258 patients with anterior circulation large vessel occlusion who received EVT in two medical centers of Taiwan were recruited. Three definitions of SICH, the European Collaborative Acute Stroke Study II (ECASS II), ECASS III, and the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST), were used. The HAT, SITS-SICH, SEDAN, and TAG risk scores were applied. Logistic regression and area under the receiver operating characteristic curve (AUC) were used to evaluate the performance of each risk model. RESULTS: In the 258 included patients (mean age, 71.9 ± 11.8 years; men, 48.1%), the observed rates of SICH according to ECASS II, ECASS III, and SITS-MOST criteria were 10.1%, 5.0%, and 4.7%, respectively. Higher glucose level (>160 mg/dL) and unsuccessful recanalization independently predicted SICH under all criteria. Among the different risk scores, only SEDAN and TAG consistently predicted SICH. SEDAN and TAG scores exhibited the highest AUC in predicting SICH for ECASS III (SEDAN 0.72, TAG 0.72) and SITS-MOST (SEDAN 0.73, TAG 0.70) criteria. CONCLUSION: Among various risk scores, the TAG and SEDAN scores best predict SICH after EVT. Higher glucose level and unsuccessful recanalization, which are included in the TAG and SEDAN scores, are independent risk factors of SICH in the present cohort, highlighting their detrimental effects.

Endovascular thrombectomy without versus with intravenous thrombolysis in acute ischemic stroke: a non-inferiority meta-analysis of randomized clinical trials.

OBJECTIVE: To conduct a meta-analysis of randomized trials to comprehensively compare the effect of endovascular thrombectomy (EVT) versus intravenous thrombolysis (IVT) plus EVT on functional independence (modified Rankin Scale (mRS) 0-2) after acute ischemic stroke due to large vessel occlusions (AIS-LVO). METHODS: We searched Pubmed, EMBASE, CENTRAL, and clinicaltrials.gov from January 2000 to February 2021 and abstracts presented at the International Stroke Conference in March 2021 to identify trials comparing EVT alone versus IVT plus EVT in AIS-LVO. Five non-inferiority margins established in the literature were assessed: -15%, -10%, -6.5%, -5%, and -1.3% for the risk difference for functional independence at 90 days. RESULTS: Four trials met the selection criteria, enrolling 1633 individuals, with 817 participants randomly assigned to EVT alone and 816 to IVT plus EVT. Crude cumulative rates of 90-day functional independence were 46.0% with EVT alone versus 45.5% with IVT plus EVT. Pooled results showed the risk difference of functional independence was 1% (95% CI -4% to 5%) between EVT alone versus IVT plus EVT. The lower 95% CI bound of -4% fell within the non-inferiority margins of -15%, -10%, -6.5%, and -5%, but not -1.3%. Pooled results also showed the risk difference between EVT alone versus IVT plus EVT was 1% (95% CI -3% to 5%) for mRS 0-1, and 1% (95% CI -1% to 3%) for symptomatic intracranial hemorrhage. CONCLUSIONS: This meta-analysis suggests that EVT alone is non-inferior to IVT plus EVT for several, but not the most stringent, non-inferiority margins.

The Clinical Influence after Implementation of Convolutional Neural Network-Based Software for Diabetic Retinopathy Detection in the Primary Care Setting.

Deep learning-based software is developed to assist physicians in terms of diagnosis; however, its clinical application is still under investigation. We integrated deep-learning-based software for diabetic retinopathy (DR) grading into the clinical workflow of an endocrinology department where endocrinologists grade for retinal images and evaluated the influence of its implementation. A total of 1432 images from 716 patients and 1400 images from 700 patients were collected before and after implementation, respectively. Using the grading by ophthalmologists as the reference standard, the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) to detect referable DR (RDR) were 0.91 (0.87-0.96), 0.90 (0.87-0.92), and 0.90 (0.87-0.93) at the image level; and 0.91 (0.81-0.97), 0.84 (0.80-0.87), and 0.87 (0.83-0.91) at the patient level. The monthly RDR rate dropped from 55.1% to 43.0% after implementation. The monthly percentage of finishing grading within the allotted time increased from 66.8% to 77.6%. There was a wide range of agreement values between the software and endocrinologists after implementation (kappa values of 0.17-0.65). In conclusion, we observed the clinical influence of deep-learning-based software on graders without the retinal subspecialty. However, the validation using images from local datasets is recommended before clinical implementation.

Effect of blood pressure parameters on functional independence in patients with acute ischemic stroke in the first 6 hours after endovascular thrombectomy.

BACKGROUND AND PURPOSE: Studies have suggested that blood pressure (BP) levels after endovascular thrombectomy (EVT) are correlated with clinical outcomes. The aim of our study was to investigate the effect of BP in different time intervals within the first 24 hours after EVT on functional outcomes. METHODS: Data of patients who received EVT for acute ischemic stroke at two institutions were reviewed. After EVT, hourly BP data were collected and divided into four time intervals: 1-6 hours, 7-12 hours, 13-18 hours, and 19-24 hours. The mean, maximum, and standard deviation (SD) of BP were calculated and compared with the outcome of interest in patients with successful recanalization. The outcome of interest was functional independence, which was defined as a 3-month modified Rankin Scale score of ≤2. RESULTS: Of 224 patients with stroke who received EVT, 166 (74.1%) (mean age 70.2±13.1 years; 49.4% men) achieved successful recanalization and 82 (49.4%) exhibited functional independence. After adjustment for possible confounders, lower mean, maximum, and SD values of systolic and diastolic BP observed in the first 6 hours after EVT were independently associated with functional independence. Furthermore, the area under the receiver operating characteristic curve values observed for BP parameters for outcome prediction in the first 6 hours were the highest across the 24-hour period following EVT. CONCLUSION: In patients with stroke who achieved successful recanalization, the first 6 hours after EVT was the key period influencing the correlation between BP and functional outcome.

Clinical Characteristics, Intraoperative Findings, and Surgical Outcomes of Canalicular Laceration Repair with Monocanalicular Stent in Asia.

PURPOSE: To report the epidemiological and clinical data as well as surgical outcomes of canalicular lacerations with Mini-Monoka insertion at a tertiary center in Taiwan and to discuss differences in traumatic pattern, pathogenesis, and surgical outcomes between Taiwan and other countries. METHODS: From 2009 to 2018, all 48 patients who underwent canalicular laceration repair with Mini-Monoka stent at a tertiary center in Taiwan were retrospectively analyzed. Demographic and clinical data and surgical outcomes were recorded. RESULTS: The mean age of the 48 patients was 38 years. Single lower canaliculus was involved in 37 (77.1%) patients, upper canaliculus in 10 (20.8%) patients, and both in 1 (2.1%) patient. The most common etiology was motorcycle accident (41.7%), and all traffic accident injuries accounted for 68.75% of cases. Subgroup classification revealed 64.6% of patients (n=31) were categorized in the deep laceration group, and lower anatomical and functional outcomes were noted in deep laceration. The mean follow-up time was 14.5 months. Overall, the anatomical success rate was 87.5%, and the functional success rate was 91.7% after stent removal. CONCLUSION: Canalicular laceration caused by traffic accidents occurred with a relatively high frequency in Taiwan. Affected patients tended to be middle-aged, and deep laceration accounted for 64.6% of patients. These were contributed by the avulsive eyelid injury mechanism caused by traffic accidents. Furthermore, the deeper lacerated site was located, and the lower anatomical and functional success rates were observed. Early repair after trauma with Mini-Monoka stents achieved good eyelid position (100%) as well as good anatomical (87.5%) and functional (91.7%) success without serious complication.

Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke Patients Receiving Thrombectomy: Standard or Low Dose Therapy?

BACKGROUND: We compared the clinical outcomes of low and standard dose recombinant tissue Plasminogen Activator (rtPA) treatment in Acute Ischemic Stroke (AIS) patients receiving Endovascular Mechanical Thrombectomy (EVT). METHODS: Between April 01, 2015 and September 30, 2017, all AIS patients admitted to the Linkou and Chiayi Chang Gung Memorial Hospital were retrospectively reviewed. Patients with large vessel occlusions, who underwent bridging therapy with rtPA and EVT, were further enrolled. The enrolled patients were categorized into low (0.6-0.7 mg/kg; LD) or standard dose (0.9 mg/kg; SD) group based on the dose of rtPA they received. Baseline characteristics, reperfusion status, and clinical outcomes were compared between the two groups. RESULTS: Forty-two patients were enrolled in the final analyses, including 13 in the LD and 29 in the SD group. In all groups analyzed, the frequencies of moderate to severe and severe stroke at discharge were significantly decreased compared to those at stroke onset (p < 0.01). Compared to the SD group, patients of the LD group had a similar rate of mortality (LD vs. SD; 0% vs. 3.4%, p = 1.00), and comparable frequencies of functional independence at 3 months after stroke onset (LD vs. SD; 33.3% vs. 44.8%, p = 0.50). The rates of symptomatic intracerebral hemorrhage were also similar between the two groups (LD vs. SD; 0% vs. 6.9%, p =1.00). CONCLUSIONS: Compared to standard dose treatment, low dose rtPA may have similar clinical efficacy and safety outcomes in AIS patients receiving bridging therapy.

Percutaneous dorsal root ganglion block for treating lumbar compression fracture-related pain.

BACKGROUND: The pain of acute compression fracture in the lumbar spine may be refractory to conservative treatment, and surgery is not an optimal choice for the elderly or infirm individuals. Moreover, even vertebroplasty can cause many side effects such as chemical leak, adjacent segment instability, and residual pain. Percutaneous dorsal root ganglion block (PDRGB) possibly is an alternative therapeutic option. In this study, we evaluated the efficacy of pain relief and the rate of adjacent level compression fracture in patients with acute compression fracture of the lumbar spine. METHODS: We retrospectively reviewed 40 patients with lumbar compression fracture from 2013 to 2015. The patients were treated with navigation-assisted CT-guided PDRGB with steroid at the pathological level and at the adjacent level above and below. Therapeutic response was evaluated using the Numerical Rating Scale (NRS); and an optimal, acceptable, and unfavorable outcome were analyzed. RESULTS: Among the 40 patients treated, initial pain relief on the first day was dramatic, and the average NRS did not change significantly up to the first-year follow-up. The highest percentage of a good outcome, at 90% (37.5% with an optimal outcome, 52.5% with an acceptable outcome), was reported at 1 week postoperatively. The percentage of optimal outcomes increased even at the 1-year follow-up. No adjacent compression fracture was found in the group treated with PDRGB alone at the 1-year follow-up. CONCLUSIONS: PDRGB is a simple, safe, and minimally invasive procedure that showed immediate and prolonged improvement of pain in lumbar osteoporotic compression fracture patients who failed conservative treatment or had residual pain after vertebroplasty. However, continuous medication for osteoporosis was still required.

Efficacy of Mastoparan-AF alone and in combination with clinically used antibiotics on nosocomial multidrug-resistant Acinetobacter baumannii.

Emergence of multidrug-resistant Acinetobacter baumannii (MDRAB) has become a critical clinical problem worldwide and limited therapeutic options for infectious diseases caused by MDRAB. Therefore, there is an urgent need for the development of new antimicrobial agents or alternative therapy to combat MDRAB infection. The aim of this study was to investigate effects of Mastoparan-AF (MP-AF), an amphipathic peptide isolated from the hornet venom of Vespa affinis with broad-spectrum antimicrobial activity, on MDRAB. As compared with clinical used antibiotics, MP-AF exhibited potent antimicrobial activity at 2-16 µg/ml against the reference strain A. baumannii ATCC 15151 and seven MDRAB clinical isolates, especially the colistin-resistant MDRAB, E0158. The synergistic antimicrobial combination study revealed that MP-AF acted synergistically with specific antibiotics, e.g., ciprofloxacin, trimethoprim/sulfamethoxazole (SXT) or colistin against some isolates of the MDRAB. It was noteworthy when MP-AF combined with SXT exhibited synergistic activity against all SXT-resistant MDRAB isolates. The synergistic combination of MP-AF and antibiotics could reduce the dosage recommended of each antimicrobial agent and improve the safety of medications with ignorable adverse effects, such as colistin with nephrotoxicity in therapeutic dose. Furthermore, MP-AF combined with antibiotics with different antimicrobial mechanisms could reduce selective pressure of antibiotics on bacteria and prevent the emergence of antimicrobial-resistant strains. Importantly, we are the first finding that MP-AF could make MDRAB from the original non-susceptibility to SXT become sensitivity. In conclusion, MP-AF alone or in combination with other antibiotics, especially SXT, is a potential candidate against MDRAB infection in clinical medicine.

A common polymorphism decreases LRP1 mRNA stability and is associated with increased plasma factor VIII levels.

The low-density lipoprotein receptor-related protein 1 (LRP1) gene is associated with increased levels of plasma factor VIII (FVIII). We aimed to explore eight functional genetic LRP1 variants for their potential roles in regulating FVIII levels and acute ischemic stroke (AIS). This genetic association study enrolled 192 patients with AIS and 134 controls. There were no significant differences in the genetic frequency of the eight functional single-nucleotide polymorphisms (SNPs) between the control and AIS groups. However, while analyzing the association between the eight SNPs and plasma FVIII levels, subjects with T/T genotype of rs1800137 (vs. CC+CT) were found to be associated with higher FVIII levels (23.5IU/dL; 95% confidence interval, 7.4-39.5IU/dL; P=0.0044) after adjusting for age, gender, estimated glomerular filtration rate, O blood type, inflammatory state, and body mass index. An analysis of the mRNA stability and abundance was designed and performed using minigene system transfected into HepG2 cells to assess the possible differences in mRNA stabilities between rs1800137 CC (rs1800137C) and TT (rs1800137T) genotypes. Site-directed mutagenesis revealed that rs1800137T accounts for the observed decrease in mRNA stability. The SNP rs1800137, located in exon 8, has been identified as an exon-splicing enhancer in silico. However, alternative splicing of LRP1 without inclusion of exon 8 was not identified. In transfected HepG2 cells, cycloheximide slowed down the degradation of the rs1800137T-containing minigene. These results demonstrate that synonymous SNP rs1800137 can lead to increased plasma FVIII levels due to decreased mRNA stability via translation-dependent mRNA degradation associated with codon optimality.

Pioglitazone for Secondary Stroke Prevention: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Pioglitazone reduced major vascular events after ischemic stroke in a recent randomized controlled trial. The purpose of this study was to conduct a meta-analysis of randomized controlled trials to evaluate the effect of pioglitazone therapy in reducing the risk of recurrent stroke in stroke patients. METHODS: Pubmed, EMBASE, Medline, and Cochrane Central Register of Controlled Trials from 1966 to March 2016 were searched to identify relevant studies. We included randomized controlled trials that included comparison of pioglitazone versus control and trials in which quantitative estimates of the hazard ratio and 95% confidence interval for recurrent stroke associated with pioglitazone therapy among stroke patients were reported. Hazard ratios with 95% confidence intervals were used as a measure of the association between use of pioglitazone and risks of recurrent stroke (ischemic and hemorrhagic) and major vascular events (nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death) after pooling data across trials. Between-study heterogeneity was assessed using the I2 statistic. RESULTS: Three randomized controlled trials with 4980 participants were identified. Use of pioglitazone in stroke patients with insulin resistance, prediabetes, and diabetes mellitus was associated with lower risk of recurrent stroke (hazard ratio 0.68; 95% confidence interval, 0.50-0.92; P=0.01) and future major vascular events (hazard ratio 0.75; 95% confidence interval, 0.64-0.87; P=0.0001). There was no heterogeneity across trials. There was no evidence of an effect on all-cause mortality and heart failure. CONCLUSIONS: Pioglitazone reduces recurrent stroke and major vascular events in ischemic stroke patients with insulin resistance, prediabetes, and diabetes mellitus.

Magnetic Resonance Perfusion Imaging Provides a Significant Tool for the Identification of Cardioembolic Stroke.

Despite advances in imaging techniques and detailed examinations to determine the etiology of a stroke, the cause still remains undetermined in about one fourth of all ischemic strokes. The aim of this prospective study was to determine whether perfusion magnetic resonance imaging (MRI) can differentiate cardioembolic stroke from large artery atherosclerosis (LAA). We recruited 17 cardioembolic stroke and 22 LAA stroke patients, who were classified according to the Trial of Org 10172 in Acute Stroke Treatment and underwent perfusion MRI within 24 hours after the onset of stroke. The patients with cardioembolic stroke had more severe initial stroke severity and larger volumes of initial and final infarct compared to those with LAA stroke. Receiver operating characteristic curve analysis showed that the ratio of time to maximum of the residual curve (Tmax) volume for a 2-, 3-, 4- or 5-s lag over Tmax volume for a 8s lag all had excellent area under the curve values (> 0.9) to predict cardioembolic stroke. After adjusting for initial National Institute of Health Stroke Scale scores, a threshold of 3.73 for (Tmax > 4s volume)/(Tmax > 8s volume) had the highest odds ratio to predict cardioembolic stroke (p=0.012; odds ratio: 58.5; 95% confident interval: 2.5-1391.1), with 87.5% sensitivity and 94.4% specificity. In conclusion, perfusion MRI could be a reliable tool to identify cardioembolic stroke with its lower collateral. This is important as it could be used to reveal the exact mechanism and provide supportive evidence to classify a stroke.