Functional and Mortality Outcomes with Medical and Surgical Therapy in Malignant Posterior Circulation Infarcts: A Systematic Review.

BACKGROUND: There remains uncertainty regarding optimal definitive management for malignant posterior circulation infarcts (MPCI). While guidelines recommend neurosurgery for malignant cerebellar infarcts that are refractory to medical therapy, concerns exist about the functional outcome and quality of life after decompressive surgery. OBJECTIVE: This study aims to evaluate the outcomes of surgical intervention compared to medical therapy in MPCI. METHODS: In this systematic review, MEDLINE, Embase and Cochrane databases were searched from inception until 2 April 2021. Studies were included if they involved posterior circulation strokes treated with neurosurgical intervention and reported mortality and functional outcome data. Data were collected according to PRISMA guidelines. RESULTS: The search yielded 6677 studies, of which 31 studies (comprising 723 patients) were included for analysis. From the included studies, we found that surgical therapy led to significant differences in mortality and functional outcomes in patients with severe disease. Neurological decline and radiological criteria were often used to decide the timing for surgical intervention, as there is currently limited evidence for preventative neurosurgery. There is also limited evidence for the superiority of one surgical modality over another. CONCLUSION: For patients with MPCI who are clinically stable at the time of presentation, in terms of mortality and functional outcome, surgical therapy appears to be equivocal to medical therapy. Reliable evidence is lacking, and further prospective studies are rendered.

Flaps for lower limb diabetic wound reconstruction: A systematic review and meta-analysis.

BACKGROUND: The treatment of chronic diabetic wounds includes wound dressing, debridement, flap surgery, and amputation. For suitable patients with nonhealing wounds, locoregional flaps or free flaps may be used. This paper aims to review the outcomes of flap surgery and identify the risk factors for flap loss. METHODS: MEDLINE, Embase, and Cochrane Library were searched. Articles reporting flap loss outcomes for flap surgery in lower limb chronic diabetic wounds were included. Case reports and case series with fewer than five patients were excluded. A subset of articles was used for revascularization subgroup analysis and another subset for meta-analysis of risk factors for flap loss. RESULTS: In the free flap group, the total flap failure rate was 7.14% and partial flap failure rate was 7.54%. The rate of major complications requiring operative takeback was 19.0%. Early mortality was 2.76%. In the locoregional flap group, the total flap failure rate was 3.24% and partial flap failure rate was 5.36%. The rate of major complications requiring operative takeback was 13.3%. There was no early mortality. The rate of free flap loss was 18.2% with revascularization, significantly higher than 6.66% without revascularization. CONCLUSIONS: Our findings concur with previously published studies on flap loss and complications in diabetic lower limb wounds. There is an increased risk of flap loss in patients who require free flap and revascularization compared to patients who only require free flap. This could be because of the fragile and fibrotic vessels found in diabetics with comorbid atherosclerosis.

The use of colchicine as an anti-inflammatory agent for stroke prevention in patients with coronary artery disease: a systematic review and meta-analysis.

OBJECTIVE: The primary objective is to evaluate the use of colchicine as an anti-inflammatory agent for stroke prevention in patients with coronary artery disease. BACKGROUND: There has been a rising number of randomized controlled trials conducted in patients with coronary artery disease on the use of colchicine in reducing cardiovascular complications. Recent publications suggest colchicine reduces the risk of stroke and other cardiovascular events. METHODS: We performed a systematic review of known trials in the current literature to characterize the clinical characteristics and outcomes of colchicine treatment in patients with coronary artery disease. A literature search was performed in PubMed, Embase and SCOPUS using a suitable keyword search strategy from inception to 4 June 2021. All studies evaluating cardiovascular outcomes of colchicine treatment in patients with coronary artery disease were included. RESULTS: The systemic review included 5 randomized controlled trials assessing a total of 11,790 patients. Majority of studies used a colchicine dosing regimen of 0.5 mg once daily, with the median follow-up duration ranging from 6 to 36 months. Meta-analytic estimates for stroke incidence highlighted a statistically significant benefit for patients that were administered colchicine compared to placebo (OR 0.47, 95% CI 0.27-0.81, p = 0.006), and a non-significant benefit for myocardial infarction. There was no significant association between colchicine treatment and the adverse effects of gastrointestinal symptoms and myopathy/myalgia. CONCLUSIONS: The use of colchicine reduces the risk of stroke in patients with a history of coronary artery disease, without a significant increase in gastrointestinal and myopathy/myalgia adverse effects.

Evaluating the safety and efficacy of intravenous thrombolysis for acute ischemic stroke patients with a history of intracerebral hemorrhage: a systematic review and meta-analysis.

Previous intracerebral hemorrhage (ICH) is labelled as a contraindication for the use of intravenous tissue plasminogen activator (IV-tPA) in acute ischemic stroke (AIS) based on expert opinion. However, there is a paucity of data available regarding the benefits and risks of IV-tPA in this population. Recent small retrospective cohort studies reporting its off-label use suggest it may be beneficial. This study aims to investigate the safety and efficacy of IV-tPA in AIS patients with previous ICH. We performed a systematic review and meta-analysis of studies reporting on IV-tPA use in AIS patients with and without previous ICH. We searched Embase, PubMed and Cochrane Library from inception to 20 April 2021. Outcomes measured included symptomatic ICH (sICH), 3-month modified Rankin Scale (mRS) score, and 3-month mortality. We included seven retrospective cohort studies comprising 5760 AIS patients who had received IV-tPA, of which 134 had previous ICH. There was no significant difference in the odds of sICH (OR 1.57, 95% CI 0.78-3.15, p = 0.21) and 3-month mRS (mRS 0-1: OR 0.78, 95% CI 0.37-1.65, p = 0.52; mRS 0-2: OR 1.07, 95% CI 0.36-3.15, p = 0.90) between patients with and without previous ICH. There was a trend towards higher 3-month mortality in patients with previous ICH (OR 1.69, 95% CI 0.98-2.91, p = 0.06), although this did not reach statistical significance. The use of IV-tPA in AIS patients with previous ICH was not associated with an increased risk of sICH or disability at 3 months. Further larger studies are needed to establish the safety and efficacy of IV-tPA use in this population.

Cilostazol for secondary stroke prevention: systematic review and meta-analysis.

BACKGROUND: Stroke is one of the leading causes of death worldwide. Cilostazol, an antiplatelet and phosphodiesterase 3 inhibitor, has not been clearly established for ischaemic stroke use. We aim to determine the efficacy and safety of cilostazol for secondary stroke prevention. METHODS: MEDLINE, EMBASE, Cochrane Library, Web of Science and ClinicalTrials.gov were searched from inception to 25 September 2020, for randomised trials comparing the efficacy and safety of cilostazol monotherapy or dual therapy with another antiplatelet regimen or placebo, in patients with ischaemic stroke. Version 2 of the Cochrane risk-of-bias tool for randomised trials (RoB 2) was used to assess study quality. This meta-analysis was reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: Eighteen randomised trials comprising 11 429 participants were included in this meta-analysis. Most trials possessed low risk of bias and were of low heterogeneity. Cilostazol significantly reduced the rate of ischaemic stroke recurrence (risk ratio, RR=0.69, 95% CI 0.58 to 0.81), any stroke recurrence (RR=0.64, 95% CI 0.54 to 0.74) and major adverse cardiovascular events (RR=0.67, 95% CI 0.56 to 0.81). Cilostazol did not significantly decrease mortality (RR=0.90, 95% CI 0.64 to 1.25) or increase the rate of good functional outcome (Modified Rankin Scale score of 0-1; RR=1.07, 95% CI 0.95 to 1.19). Cilostazol demonstrated favourable safety profile, significantly reducing the risk of intracranial haemorrhage (RR=0.46, 95% CI 0.31 to 0.68) and major haemorrhagic events (RR=0.49, 95% CI 0.34 to 0.70). CONCLUSIONS: Cilostazol demonstrated superior efficacy and safety profiles compared with traditional antiplatelet regimens such as aspirin and clopidogrel for secondary stroke prevention but does not appear to affect functional outcomes. Future randomised trials can be conducted outside East Asia, or compare cilostazol with a wider range of antiplatelet agents.

Intra-Arterial Adjunctive Medications for Acute Ischemic Stroke During Mechanical Thrombectomy: A Meta-Analysis.

BACKGROUND AND PURPOSE: In patients with acute ischemic stroke with large vessel occlusion, the role of intra-arterial adjunctive medications (IAMs), such as urokinase, tPA (tissue-type plasminogen activator), or glycoprotein IIb/IIIa inhibitors, during mechanical thrombectomy (MT) has not been clearly established. We aim to evaluate the efficacy and safety of concomitant or rescue IAM for acute ischemic stroke with large vessel occlusion patients undergoing MT. METHODS: We searched Medline, Embase, and Cochrane Stroke Group Trials Register databases from inception until March 13, 2020. We analyzed all studies with patients diagnosed with acute ischemic stroke with large vessel occlusion in the anterior or posterior circulation that provided data for the two treatment arms, (1) MT+IAM and (2) MT only, and also reported on at least one of the following efficacy outcomes, recanalization and 90-day modified Rankin Scale, or safety outcomes, symptomatic intracranial hemorrhage and 90-day mortality. Data were collated in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Sixteen nonrandomized observational studies with a total of 4581 patients were analyzed. MT only was performed in 3233 (70.6%) patients, while 1348 (29.4%) patients were treated with both MT and IAM. As compared with patients treated with MT alone, patients treated with combination therapy (MT+IAM) had a higher likelihood of achieving good functional outcome (risk ratio, 1.13 [95% CI, 1.03-1.24]) and a lower risk of 90-day mortality (risk ratio, 0.82 [95% CI, 0.72-0.94]). There was no significant difference in successful recanalization (risk ratio, 1.02 [95% CI, 0.99-1.06]) and symptomatic intracranial hemorrhage between the two groups (risk ratio, 1.13 [95% CI, 0.87-1.46]). CONCLUSIONS: In acute ischemic stroke with large vessel occlusion, the use of IAM together with MT may achieve better functional outcomes and lower mortality rates. Randomized controlled trials are warranted to establish the safety and efficacy of IAM as adjunctive treatment to MT.

Use of Smartphones to Detect Diabetic Retinopathy: Scoping Review and Meta-Analysis of Diagnostic Test Accuracy Studies.

BACKGROUND: Diabetic retinopathy (DR), a common complication of diabetes mellitus, is the leading cause of impaired vision in adults worldwide. Smartphone ophthalmoscopy involves using a smartphone camera for digital retinal imaging. Utilizing smartphones to detect DR is potentially more affordable, accessible, and easier to use than conventional methods. OBJECTIVE: This study aimed to determine the diagnostic accuracy of various smartphone ophthalmoscopy approaches for detecting DR in diabetic patients. METHODS: We performed an electronic search on the Medical Literature Analysis and Retrieval System Online (MEDLINE), EMBASE, and Cochrane Library for literature published from January 2000 to November 2018. We included studies involving diabetic patients, which compared the diagnostic accuracy of smartphone ophthalmoscopy for detecting DR to an accurate or commonly employed reference standard, such as indirect ophthalmoscopy, slit-lamp biomicroscopy, and tabletop fundus photography. Two reviewers independently screened studies against the inclusion criteria, extracted data, and assessed the quality of included studies using the Quality Assessment of Diagnostic Accuracy Studies-2 tool, with disagreements resolved via consensus. Sensitivity and specificity were pooled using the random effects model. A summary receiver operating characteristic (SROC) curve was constructed. This review is reported in line with the Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies guidelines. RESULTS: In all, nine studies involving 1430 participants were included. Most studies were of high quality, except one study with limited applicability because of its reference standard. The pooled sensitivity and specificity for detecting any DR was 87% (95% CI 74%-94%) and 94% (95% CI 81%-98%); mild nonproliferative DR (NPDR) was 39% (95% CI 10%-79%) and 95% (95% CI 91%-98%); moderate NPDR was 71% (95% CI 57%-81%) and 95% (95% CI 88%-98%); severe NPDR was 80% (95% CI 49%-94%) and 97% (95% CI 88%-99%); proliferative DR (PDR) was 92% (95% CI 79%-97%) and 99% (95% CI 96%-99%); diabetic macular edema was 79% (95% CI 63%-89%) and 93% (95% CI 82%-97%); and referral-warranted DR was 91% (95% CI 86%-94%) and 89% (95% CI 56%-98%). The area under SROC curve ranged from 0.879 to 0.979. The diagnostic odds ratio ranged from 11.3 to 1225. CONCLUSIONS: We found heterogeneous evidence showing that smartphone ophthalmoscopy performs well in detecting DR. The diagnostic accuracy for PDR was highest. Future studies should standardize reference criteria and classification criteria and evaluate other available forms of smartphone ophthalmoscopy in primary care settings.

Comparing the efficacy and safety of direct oral anticoagulants with vitamin K antagonist in cerebral venous thrombosis.

Cerebral venous thrombosis (CVT) causes significant disability and mortality. Current guidelines for CVT management support the initial use of unfractionated heparin or low molecular weight heparin followed by longer-term oral vitamin K antagonist (VKA). There has been increasing, albeit limited, evidence for the use of direct oral anticoagulants (DOAC) as an alternative to VKA. We performed a systematic review and meta-analysis of studies that compared the safety and efficacy of DOACs to VKA in treating CVT. A comprehensive literature search was carried out in Medline, Embase and Cochrane Stroke Group Trials Register using a suitable keyword/MeSH term search strategy. All studies published in English comparing outcomes of patients with CVT treated with DOAC or VKA were included. In total, 6 studies (5 observational studies and 1 randomized clinical trial) comprising 412 patients (age range 16-83 years) were analyzed. DOAC was used in 151 patients, while 261 received VKA. The follow-up period was 3-11 months. The efficacy of DOACs was comparable with VKA in terms of partial or full thrombus recanalization (RR 1.02, 95% CI 0.89-1.16) and excellent functional recovery with modified Rankin scale < 2 (RR 1.02, 95% CI 0.93-1.13). Patients treated with DOAC developed lower major bleeding events when compared to VKA, although this did not reach statistical significance (RR 0.44, 95% CI 0.12-1.59). We provide preliminary evidence to support DOAC as effective and safe alternatives to VKA in CVT treatment. We await the results of upcoming randomized trials to further support our results and validate the use of DOAC.

Use of smartphones for detecting diabetic retinopathy: a protocol for a scoping review of diagnostic test accuracy studies.

INTRODUCTION: Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus and the leading cause of impaired vision in adults worldwide. Early detection and treatment for DR could improve patient outcomes. Traditional methods of detecting DR include the gold standard Early Treatment Diabetic Retinopathy Study seven standard fields fundus photography, ophthalmoscopy and slit-lamp biomicroscopy. These modalities can be expensive, difficult to access and require involvement of specialised healthcare professionals. With the development of mobile phone technology, there is a growing interest in their use for DR identification as this approach is potentially more affordable, accessible and easier to use. Smartphones can be employed in a variety of ways for ophthalmoscopy including the use of smartphone camera, various attachments and artificial intelligence for obtaining and grading of retinal images. The aim of this scoping review is to determine the diagnostic test accuracy of various smartphone ophthalmoscopy approaches for detecting DR in diabetic patients. METHODS AND ANALYSIS: We will perform an electronic search of MEDLINE, Embase and Cochrane Library for literature published from 2000 onwards. Two reviewers will independently analyse studies for eligibility and assess study quality using the QUADAS-2 tool. Data for a 2⨉2 contingency table will be extracted. If possible, we will pool sensitivity and specificity data using the random-effects model and construct a summary receiver operating characteristic curve. In case of high heterogeneity, we will present the findings narratively. Subgroup analysis and sensitivity analysis will be performed where appropriate. ETHICS AND DISSEMINATION: This scoping review aims to provide an overview of smartphone ophthalmoscopy in DR identification. It will present findings on the accuracy of smartphone ophthalmoscopy in detecting DR, identify gaps in the literature and provide recommendations for future research. This review does not require ethical approval as we will not collect primary data.