Association Between Calcium Supplementation and the Risk of Cardiovascular Disease and Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Some observational studies and randomised controlled trials (RCTs) have reported an association between calcium supplementation and increased risk of cardiovascular disease. Previous meta-analyses on the topic, based on data from RCTs and observational studies, have contradictory findings. This meta-analysis was conducted to determine the difference in associated risks of calcium supplementation with cardiovascular disease and stroke in RCTs. METHODS: Relevant studies published from database inception to 6 August 2021 were sourced from PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials. Any RCTs focusing on the relationship between calcium supplementation and incidence of cardiovascular disease or stroke were included. Articles were screened independently by two authors, according to the PICO criteria, with disagreements resolved by a third author. RESULTS: Twelve RCTs were included in the meta-analysis. Calcium supplementation was not associated with myocardial infarction, total stroke, heart failure admission, and all-cause/cardiovascular mortality. Subgroup analysis focusing on calcium monotherapy/calcium co-therapy with vitamin D, female sex, follow-up duration, and geographical region did not affect the findings. CONCLUSION: Calcium supplementation was not associated with myocardial infarction, total stroke, heart failure admission, and cardiovascular/all-cause mortality. Further studies are required to examine and understand these associations.

A systematic review and meta-analysis of non-vitamin K antagonist oral anticoagulants vs vitamin K antagonists after transcatheter aortic valve replacement in patients with atrial fibrillation.

PURPOSE: Transcatheter aortic valve replacement (TAVR) is increasingly carried out in patients with aortic valvular conditions. Atrial fibrillation (AF) is a common comorbidity among patients undergoing TAVR. Despite this, there remains a paucity of data and established guidelines regarding anticoagulation use post-TAVR in patients with AF. METHODS: Four databases were searched from inception until 12 October 2021. A title and abstract sieve, full-text review and data extraction were conducted by independent authors, and articles including patients without AF were excluded. The Review Manager (Version 5.4) was utilised in data analysis. RESULTS: A total of 25,199 post-TAVR patients with AF were included from seven articles, with 9764 patients on non-vitamin K antagonist oral anticoagulants (NOAC) and 15,435 patients on vitamin K antagonists (VKA). In this analysis, there was a significantly lower risk of all-cause mortality at 1 year (RR: 0.75, CI: 0.58-0.97, p = 0.04, I2 = 56%), and bleeding at 1 year (RR: 0.73, CI: 0.68-0.79, p = < 0.00001, I2 = 0%), between patients on NOAC and VKA. There were no detectable differences between patients on NOAC and VKA for all-cause mortality at 2 years, stroke within 30 days, stroke within 1 year, ischaemic stroke at 1 year and life-threatening bleeding at 30 days. CONCLUSION: While the results of this analysis reveal NOAC as a potential alternate treatment modality to VKA in post-TAVR patients with AF, further research is needed to determine the full safety and efficacy profile of NOAC (PROSPERO: CRD42021283548).

Intravenous thrombolysis and endovascular thrombectomy for acute ischaemic stroke in patients with Moyamoya disease - a systematic review and meta-summary of case reports.

BACKGROUND AND AIMS: Patients with Moyamoya disease (MMD) can present with ischaemic or haemorrhagic stroke. There is no good evidence for treatment strategies in MMD-associated acute ischaemic stroke (AIS), particularly for treatments like intravenous thrombolysis (IVT) and endovascular thrombectomy (ET). As the intracranial vessels are friable in MMD, and the risk of bleeding is high, the use of IVT and ET is controversial. To clarify the safety and efficacy of IVT/ET in the treatment of MMD-associated AIS, we performed a systematic review and meta-summary to examine this issue. METHODS: A systematic search was performed from four electronic databases: PubMed (MEDLINE), Cochrane Library, EMBASE and Scopus, profiling data from inception till 21 November 2021, as well as, manually on Google Scholar. RESULTS: Ten case reports detailing 10 MMD patients presenting with AIS and undergoing IVT or ET, or both, were included in the analysis. The median National Institute of Health Stroke Scale score at presentation was 10 (Interquartile Range [IQR] = 6.0-16.5). IVT alone was instituted in 6 patients, primary ET was attempted in 2, and 2 had received bridging IVT with ET. Of the 4 patients who underwent ET, 2 patients achieved successful reperfusion (modified Thrombolysis In Cerebral Infarction scale [mTICI] ≥ 2b). In terms of functional outcomes, One patient achieved complete recovery (modified Rankin Scale 0), 4 patients attained improvement in neurological status, and 4 had no improvement, whilst functional outcome was unreported in 1 patient. No patient experienced symptomatic intracranial haemorrhage. CONCLUSIONS: In this systematic review and meta-summary, the utility of IVT and ET in MMD-associated AIS appears feasible in selected cases. Further larger cohort studies are required to evaluate these treatment approaches. HIGHLIGHTS: · AIS in MMD was typically managed with bypass surgery but not via thrombolysis or thrombectomy. · In this meta-summary, all patients treated with thrombolysis and/or thrombectomy survived and some experienced symptomatic and/or functional improvement. · Further larger cohort studies are necessary for investigating the role of thrombolysis and/or thrombectomy as treatment of AIS in MMD.

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.

Phase Ib Study of Enzalutamide with or Without Sorafenib in Patients with Advanced Hepatocellular Carcinoma.

LESSONS LEARNED: Androgen receptor as assessed by immunohistochemistry is expressed in a high proportion of patients with hepatocellular carcinoma (HCC). Enzalutamide at 160 mg orally daily is safe and tolerable in patients with advanced HCC but has no single-agent antitumor activity. Enzalutamide, a CYP3A4 inducer, at a standard dose of 160 mg reduces the exposure of sorafenib, a CYP3A4 substrate. Enzalutamide and sorafenib is safe and tolerable in patients with advanced HCC, but the addition of enzalutamide to sorafenib did not enhance the antitumor activity of sorafenib. BACKGROUND: Androgen receptor (AR) interference is deleterious to hepatocellular carcinoma (HCC) in preclinical models. METHODS: This is a multicenter, phase Ib study of enzalutamide ± sorafenib in patients with advanced HCC. In part 1, a 3 + 3 dose de-escalation design with expansion established the recommended phase II dose (RP2D) of enzalutamide in patients in whom sorafenib treatment had failed. In part 2, a 3 + 3 dose escalation with expansion established the safety of enzalutamide with sorafenib in treatment-naive patients with HCC. Secondary objectives included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), pharmacokinetics (PK), and determination of AR expression by immunohistochemistry. A 7-day run-in with sorafenib alone in part 2 allowed assessment of the impact of enzalutamide on sorafenib pharmacokinetics. RESULTS: In part 1, 16 patients received enzalutamide 160 mg daily. No dose-limiting toxicity (DLT) occurred; 1 patient required dose reduction. Responses were not observed; median PFS and OS were 1.8 (95% confidence interval [CI]: 1.6-3.6) and 7 (95% CI: 3.6 to not reached [NR]) months, respectively. In part 2, patients received sorafenib 400 mg daily (4) or twice a day (8) both with enzalutamide at the recommended phase II dose-no DLTs were observed. ORR was 10% (95% CI: 0.3-44.5), and median PFS and OS were 2.9 (95% CI: 1.6 to NR) and 6.7 (95% CI: 4.6 to NR) months, respectively. Enzalutamide reduced sorafenib exposure by 60%. Tumor AR expression did not associate with outcome. CONCLUSION: Enzalutamide is ineffective in HCC; further development is not supported by this study.

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.

Impact of the COVID-19 pandemic on hyperacute stroke treatment: experience from a comprehensive stroke centre in Singapore.

The Coronavirus disease 2019 (COVID-19) pandemic is rapidly evolving and affecting healthcare systems across the world. Singapore has escalated its alert level to Disease Outbreak Response System Condition (DORSCON) Orange, signifying severe disease with community spread. We aimed to study the overall volume of AIS cases and the delivery of hyperacute stroke services during DORSCON Orange. This was a single-centre, observational cohort study performed at a comprehensive stroke centre responsible for AIS cases in the western region of Singapore, as well as providing care for COVID-19 patients. All AIS patients reviewed as an acute stroke activation in the Emergency Department (ED) from November 2019 to April 2020 were included. System processes timings, treatment and clinical outcome variables were collected. We studied 350 AIS activation patients admitted through the ED, 206 (58.9%) pre- and 144 during DORSCON Orange. Across the study period, number of stroke activations showed significant decline (p = 0.004, 95% CI 6.513 to - 2.287), as the number of COVID-19 cases increased exponentially, whilst proportion of activations receiving acute recanalization therapy remained stable (p = 0.519, 95% CI - 1.605 to 2.702). Amongst AIS patients that received acute recanalization therapy, early neurological outcomes in terms of change in median NIHSS at 24 h (-4 versus -4, p = 0.685) were largely similar between the pre- and during DORSCON orange periods. The number of stroke activations decreased while the proportion receiving acute recanalization therapy remained stable in the current COVID-19 pandemic in Singapore.

Utility of a multidisciplinary tumor board in the management of pancreatic and upper gastrointestinal diseases: an observational study.

BACKGROUND & OBJECTIVES: Multidisciplinary tumor boards (MDTBs) are frequently employed in cancer centers but their value has been debated. We reviewed the decision-making process and resource utilization of our MDTB to assess its utility in the management of pancreatic and upper gastrointestinal tract conditions. METHODS: A prospectively-collected database was reviewed over a 12-month period. The primary outcome was change in management plan as a result of case discussion. Secondary outcomes included resources required to hold MDTB, survival, and adherence to treatment guidelines. RESULTS: Four hundred seventy cases were reviewed. MDTB resulted in a change in the proposed plan of management in 101 of 402 evaluable cases (25.1%). New plans favored obtaining additional diagnostic workup. No recorded variables were associated with a change in plan. For newly-diagnosed cases of pancreatic ductal adenocarcinoma (n = 33), survival time was not impacted by MDTB (p = .154) and adherence to National Comprehensive Cancer Network guidelines was 100%. The estimated cost of physician time per case reviewed was $190. CONCLUSIONS: Our MDTB influences treatment decisions in a sizeable number of cases with excellent adherence to national guidelines. However, this requires significant time expenditure and may not impact outcomes. Regular assessments of the effectiveness of MDTBs should be undertaken.

Good Intracranial Collaterals Trump Poor ASPECTS (Alberta Stroke Program Early CT Score) for Intravenous Thrombolysis in Anterior Circulation Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: In acute ischemic stroke, large early infarct size estimated by the Alberta Stroke Program Early CT Score (ASPECTS) is associated with poorer outcomes and is a relative contraindication for recanalization therapies. The state of the intracranial collateral circulation influences the functional outcome and may be a variable to consider before thrombolysis. We evaluated the prognostic effect of the collateral circulation in patients with thrombolyzed acute ischemic stroke who have large early infarct sizes as indicated by low ASPECTS. MATERIALS AND METHODS: Patients with anterior circulation acute ischemic stroke who received a computed tomographic angiogram and subsequent treatment with intravenous tissue-type plasminogen activator from 2010 to 2013 were studied. Two independent neuroradiologists determined their ASPECTS. We stratified patients using ASPECTS into 2 groups: large volume infarcts (ASPECTS≤7 points) and small volume infarcts (ASPECTS 8-10). In addition, we evaluated a third group with very large volume infarcts (ASPECTS≤5 points). We then analyzed the 3 subgroups using the Maas, Tan, and ASPECTS-collaterals grading systems of the computed tomographic angiogram intracranial collaterals. Good outcomes were defined by modified Rankin Scale score of 0 to 2 at 3 months. RESULTS: A total of 300 patients were included in the final analysis. For patients with very large volume infarcts (ASPECTS≤5 points), univariable analysis showed that younger age, male sex, lower National Institute of Health Stroke Scale (NIHSS), lower systolic blood pressure, and good collaterals by Maas, Tan, or ASPECTS-collaterals grading were predictors of good outcomes. On multivariate analysis, younger age (odds ratio, 0.93; 95% confidence interval, 0.89-0.97; P=0.002) and good collaterals by ASPECTS-collaterals system (odds ratio, 1.34; 95% confidence interval, 1.15-1.57; P<0.001) were associated with good outcomes. CONCLUSIONS: In patients with large and very large volume infarcts, good collaterals as measured by the ASPECTS-collaterals system is associated with improved outcomes and can help select patients for intravenous thrombolysis.

Association of Hearing Aids and Cochlear Implants With Cognitive Decline and Dementia: A Systematic Review and Meta-analysis.

Importance: Hearing loss is associated with cognitive decline. However, it is unclear if hearing restorative devices may have a beneficial effect on cognition. Objective: To evaluate the associations of hearing aids and cochlear implants with cognitive decline and dementia. Data Sources: PubMed, Embase, and Cochrane databases for studies published from inception to July 23, 2021. Study Selection: Randomized clinical trials or observational studies published as full-length articles in peer-reviewed journals relating to the effect of hearing interventions on cognitive function, cognitive decline, cognitive impairment, and dementia in patients with hearing loss. Data Extraction and Synthesis: The review was conducted in accordance with Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) reporting guidelines. Two authors independently searched the PubMed, Embase, and Cochrane databases for studies relating to the effect of hearing interventions on cognitive decline and dementia in patients with hearing loss. Main Outcomes and Measures: Maximally adjusted hazard ratios (HRs) were used for dichotomous outcomes and ratio of means for continuous outcomes. Sources of heterogeneity were investigated using sensitivity and subgroup analyses, and publication bias was assessed using visual inspection, the Egger test, and trim and fill. Results: A total of 3243 studies were screened; 31 studies (25 observational studies, 6 trials) with 137 484 participants were included, of which 19 (15 observational studies, 4 trials) were included in quantitative analyses. Meta-analysis of 8 studies, which had 126 903 participants, had a follow-up duration ranging from 2 to 25 years, and studied long-term associations between hearing aid use and cognitive decline, showed significantly lower hazards of any cognitive decline among hearing aid users compared with participants with uncorrected hearing loss (HR, 0.81; 95% CI, 0.76-0.87; I2 = 0%). Additionally, meta-analysis of 11 studies with 568 participants studying the association between hearing restoration and short-term cognitive test score changes revealed a 3% improvement in short-term cognitive test scores after the use of hearing aids (ratio of means, 1.03; 95% CI, 1.02-1.04, I2 = 0%). Conclusions and Relevance: In this meta-analysis, the usage of hearing restorative devices by participants with hearing loss was associated with a 19% decrease in hazards of long-term cognitive decline. Furthermore, usage of these devices was significantly associated with a 3% improvement in cognitive test scores that assessed general cognition in the short term. A cognitive benefit of hearing restorative devices should be further investigated in randomized trials.

Benefit and risk of intravenous alteplase in patients with acute large vessel occlusion stroke and low ASPECTS.

BACKGROUND: The benefit of best medical treatment including intravenous alteplase (IVT) before mechanical thrombectomy (MT) in patients with acute ischemic stroke and extensive early ischemic changes on baseline CT remains uncertain. The purpose of this study was to evaluate the benefit of IVT for patients with low ASPECTS (Alberta Stroke Programme Early CT Score) compared with patients with or without MT. METHODS: This multicenter study pooled consecutive patients with anterior circulation acute stroke and ASPECTS≤5 to analyze the impact of IVT on functional outcome, and to compare bridging IVT with direct MT. Functional endpoints were the rates of good (modified Rankin Scale (mRS) score ≤2) and very poor (mRS ≥5) outcome at day 90. Safety endpoint was the occurrence of symptomatic intracranial hemorrhage (sICH). RESULTS: 429 patients were included. 290 (68%) received IVT and 168 (39%) underwent MT. The rate of good functional outcome was 14.4% (95% CI 7.1% to 21.8%) for patients who received bridging IVT and 24.4% (95% CI 16.5% to 32.2%) for those who underwent direct MT. The rate of sICH was significantly higher in patients with bridging IVT compared with direct MT (17.8% vs 6.4%, p=0.004). In multivariable logistic regression analysis, IVT was significantly associated with very poor outcome (OR 2.22, 95% CI 1.05 to 4.73, p=0.04) and sICH (OR 3.44, 95% CI 1.18 to 10.07, p=0.02). Successful recanalization, age, and ASPECTS were associated with good functional outcome. CONCLUSIONS: Bridging IVT in patients with low ASPECTS was associated with very poor functional outcome and an increased risk of sICH. The benefit of this treatment should therefore be carefully weighed in such scenarios. Further randomized controlled trials are required to validate our findings.

Distal medium vessel occlusions in acute ischaemic stroke - Stent retriever versus direct aspiration: A systematic review and meta-analysis.

BACKGROUND: Acute ischaemic stroke due to distal medium vessel occlusion (AIS-DMVO) causes significant morbidity. Endovascular thrombectomy advancement has made treating AIS-DMVO with stent retrievers (SR) and aspiration catheters (AC) possible, however the optimal technique remains unknown. We performed a systematic review and meta-analysis to investigate the efficacy and safety of SR use compared to purely AC use in patients with AIS-DMVO. METHODS: We systematically searched PubMed, Cochrane Library and EMBASE, from inception to 2nd September 2022, for studies comparing SR or primary combined (SR/PC) against AC in AIS-DMVO. We adopted the Distal Thrombectomy Summit Group's definition of DMVO. Efficacy outcomes were functional independence (modified Rankin Scale (mRS) 0-2 at 90 days), first pass effect (modified Thrombolysis in Cerebral Infarction scale (mTICI) 2c-3 or expanded Thrombolysis in Cerebral Infarction scale (eTICI) 2c-3 at first pass), successful final recanalisation (mTICI or eTICI 2b-3), and excellent final recanalisation (mTICI or eTICI 2c-3). Safety outcomes were symptomatic intracranial haemorrhage (sICH) and 90-day mortality. RESULTS: 12 cohort studies and 1 randomised-controlled trial were included, involving 1881 patients with 1274 receiving SR/PC and 607 receiving AC only. SR/PC achieved higher odds of functional independence (odds ratio (OR) 1.33, 95% confidence interval (CI) 1.06-1.67) and lower odds of mortality (OR 0.69, 95% CI 0.50-0.94) than AC. Odds of successful/excellent recanalisation and sICH were similar between both groups. Stratified to compare only SR and only AC, the use of only SR, achieved significantly higher odds of successful recanalisation as compared to only AC (OR 1.80, 95% CI 1.17-2.78). CONCLUSION: There is potential for efficacy and safety benefits in SR/PC use as compared to AC only in AIS-DMVO. Further trials are necessary to validate the efficacy and safety of SR use in AIS-DMVO.

Efficacy of covid-19 vaccines in immunocompromised patients: systematic review and meta-analysis.

OBJECTIVE: To compare the efficacy of covid-19 vaccines between immunocompromised and immunocompetent people. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, Central Register of Controlled Trials, COVID-19 Open Research Dataset Challenge (CORD-19), and WHO covid-19 databases for studies published between 1 December 2020 and 5 November 2021. ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched in November 2021 to identify registered but as yet unpublished or ongoing studies. STUDY SELECTION: Prospective observational studies comparing the efficacy of covid-19 vaccination in immunocompromised and immunocompetent participants. METHODS: A frequentist random effects meta-analysis was used to separately pool relative and absolute risks of seroconversion after the first and second doses of a covid-19 vaccine. Systematic review without meta-analysis of SARS-CoV-2 antibody titre levels was performed after first, second, and third vaccine doses and the seroconversion rate after a third dose. Risk of bias and certainty of evidence were assessed. RESULTS: 82 studies were included in the meta-analysis. Of these studies, 77 (94%) used mRNA vaccines, 16 (20%) viral vector vaccines, and 4 (5%) inactivated whole virus vaccines. 63 studies were assessed to be at low risk of bias and 19 at moderate risk of bias. After one vaccine dose, seroconversion was about half as likely in patients with haematological cancers (risk ratio 0.40, 95% confidence interval 0.32 to 0.50, I2=80%; absolute risk 0.29, 95% confidence interval 0.20 to 0.40, I2=89%), immune mediated inflammatory disorders (0.53, 0.39 to 0.71, I2=89%; 0.29, 0.11 to 0.58, I2=97%), and solid cancers (0.55, 0.46 to 0.65, I2=78%; 0.44, 0.36 to 0.53, I2=84%) compared with immunocompetent controls, whereas organ transplant recipients were 16 times less likely to seroconvert (0.06, 0.04 to 0.09, I2=0%; 0.06, 0.04 to 0.08, I2=0%). After a second dose, seroconversion remained least likely in transplant recipients (0.39, 0.32 to 0.46, I2=92%; 0.35, 0.26 to 0.46), with only a third achieving seroconversion. Seroconversion was increasingly likely in patients with haematological cancers (0.63, 0.57 to 0.69, I2=88%; 0.62, 0.54 to 0.70, I2=90%), immune mediated inflammatory disorders (0.75, 0.69 to 0.82, I2=92%; 0.77, 0.66 to 0.85, I2=93%), and solid cancers (0.90, 0.88 to 0.93, I2=51%; 0.89, 0.86 to 0.91, I2=49%). Seroconversion was similar between people with HIV and immunocompetent controls (1.00, 0.98 to 1.01, I2=0%; 0.97, 0.83 to 1.00, I2=89%). Systematic review of 11 studies showed that a third dose of a covid-19 mRNA vaccine was associated with seroconversion among vaccine non-responders with solid cancers, haematological cancers, and immune mediated inflammatory disorders, although response was variable in transplant recipients and inadequately studied in people with HIV and those receiving non-mRNA vaccines. CONCLUSION: Seroconversion rates after covid-19 vaccination were significantly lower in immunocompromised patients, especially organ transplant recipients. A second dose was associated with consistently improved seroconversion across all patient groups, albeit at a lower magnitude for organ transplant recipients. Targeted interventions for immunocompromised patients, including a third (booster) dose, should be performed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021272088.

Preprocedural Imaging : A Review of Different Radiological Factors Affecting the Outcome of Thrombectomy.

BACKGROUND: Endovascular treatment (EVT) has strong evidence for its effectiveness in treatment of acute ischemic stroke (AIS); however, up to half of the patients who undergo EVT still do not have good functional outcomes. Various prethrombectomy radiological factors have been shown to be associated with good clinical outcomes and may be the key to better functional outcomes, reduced complications, and reduced mortality. In this paper, we reviewed the current literature on these imaging parameters so they can be employed to better estimate the probability of procedural success, therefore allowing for more effective preprocedural planning of EVT strategies. We reviewed articles in the literature related to imaging factors which have been shown to be associated with EVT success. The factors which are reviewed in this paper included: anatomical factors such as 1) the type of aortic arch and its characteristics, 2) the characteristics of the thrombus such as length, clot burden, permeability, location, 3) the middle cerebral artery features including the tortuosity and underlying intracranial stenosis, 4) perfusion scans estimating the volume of infarct and the penumbra and 5) the effect of collaterals on the procedure. The prognostic effect of each factor on the successful outcome of EVT is described. The identification of preprocedural thrombectomy imaging factors can help to improve the chances of recanalization, functional outcomes, and mortality. It allows the interventionist to make time-sensitive decisions in the treatment of acute ischemic stroke.

Deep Cerebral Venous Thrombosis Treatment : Endovascular Case using Aspiration and Review of the Various Treatment Modalities.

BACKGROUND: Deep cerebral venous thrombosis (CVT) is an uncommon condition with a high morbidity and mortality. The optimal treatment approach for deep CVT remains uncertain and due to its low prevalence, randomized trials are not feasible. We showcase a straight sinus thrombosis treated with a large bore aspiration and performed a meta-analysis of the available literature to characterize and evaluate the various treatment modalities for patients with deep CVT. METHODS: We conducted a systematic search in PubMed, EMBASE and Ovid Medline using appropriate keywords/MESH terms search strategy. All patients with thrombosis involving the deep venous sinuses were included if treatment records were available. Outcome measures included recanalization of the affected sinus, good functional outcome assessed by a modified Rankin scale (mRS) of 0-2 or reported independent functional outcomes, permanent neurological deficits, further hemorrhage and mortality. RESULTS: A total of 69 studies comprising 120 patients were included in the analysis. Anticoagulation was the most common treatment (85.8%), whilst local intrasinus thrombolysis was performed in 40.0% of the patients and mechanical endovascular modalities were employed in 20.0% of the patients. Recanalization of the occluded sinus was seen in 83.5% of the patients while 62.6% patients achieved good functional outcome. There was considerable morbidity with 60.7% having a permanent neurological deficit, 23.3% having further hemorrhage after admission and 18.6% mortality. In the cohort receiving anticoagulation, 65.3% achieved good outcome but intracranial hemorrhage at presentation was associated with poorer outcome, permanent deficits, further bleeding and mortality. CONCLUSION: Anticoagulation is an effective treatment strategy for deep CVT; however, patients with intracranial hemorrhage at presentation often have poorer outcomes and early endovascular strategies could be considered in this subgroup.

Assessment of Hepatic Arterial Infusion of Floxuridine in Combination With Systemic Gemcitabine and Oxaliplatin in Patients With Unresectable Intrahepatic Cholangiocarcinoma: A Phase 2 Clinical Trial.

IMPORTANCE: Unresectable intrahepatic cholangiocarcinoma (IHC) carries a poor prognosis, with a median overall survival (OS) of 11 months. Hepatic arterial infusion (HAI) of high-dose chemotherapy may have potential benefit in these patients. OBJECTIVE: To evaluate clinical outcomes when HAI chemotherapy is combined with systemic chemotherapy in patients with unresectable IHC. DESIGN, SETTING, AND PARTICIPANTS: A single-institution, phase 2 clinical trial including 38 patients was conducted with HAI floxuridine plus systemic gemcitabine and oxaliplatin in patients with unresectable IHC at Memorial Sloan Kettering Cancer Center between May 20, 2013, and June 27, 2019. A confirmatory phase 1/2 study using the same therapy was conducted during the same time period at Washington University in St Louis. Patients with histologically confirmed, unresectable IHC were eligible. Resectable metastatic disease to regional lymph nodes and prior systemic therapy were permitted. Patients with distant metastatic disease were excluded. INTERVENTIONS: Hepatic arterial infusion of floxuridine and systemic administration of gemcitabine and oxaliplatin. MAIN OUTCOMES AND MEASURES: The primary outcome was progression-free survival (PFS) of 80% at 6 months. RESULTS: For the phase 2 clinical trial at Memorial Sloan Kettering Cancer Center, 42 patients with unresectable IHC were included and, of these, 38 patients were treated (13 [34%] men; median [range] age at diagnosis, 64 [39-81] years). The median follow-up was 30.5 months. Twenty-two patients (58%) achieved a partial radiographic response, and 32 patients (84%) achieved disease control at 6 months. Four patients had sufficient response to undergo resection, and 1 patient had a complete pathologic response. The median PFS was 11.8 months (1-sided 90% CI, 11.1) with a 6-month PFS rate of 84.1% (90% CI, 74.8%-infinity), thereby meeting the primary end point (6-month PFS rate, 80%). The median OS was 25.0 months (95% CI, 20.6-not reached), and the 1-year OS rate was 89.5% (95% CI, 80.2%-99.8%). Patients with resectable regional lymph nodes (18 [47%]) showed no difference in OS compared with patients with node-negative disease (24-month OS: lymph node negative: 60%; 95% CI, 40%-91% vs lymph node positive: 50%; 95% CI, 30%-83%; P = .66). Four patients (11%) had grade 4 toxic effects requiring removal from the study (1 portal hypertension, 2 gastroduodenal artery aneurysms, 1 infection in the pump pocket). Subgroup analysis showed significant improvement in survival in patients with IDH1/2 mutated tumors (2-year OS, 90%; 95% CI, 73%-99%) vs wild-type (2-year OS, 33%; 95% CI, 18%-63%) (P = .01). In the Washington University in St Louis confirmatory cohort, 9 patients (90%) achieved disease control at 6 months; the most common grade 3 toxic effect was elevated results of liver function tests, and median PFS was 12.8 months (1-sided 90% CI, 6.4). CONCLUSIONS AND RELEVANCE: Hepatic arterial infusion plus systemic chemotherapy appears to be highly active and tolerable in patients with unresectable IHC; further evaluation is warranted.

Acute Health Impacts of the Southeast Asian Transboundary Haze Problem-A Review.

Air pollution has emerged as one of the world's largest environmental health threats, with various studies demonstrating associations between exposure to air pollution and respiratory and cardiovascular diseases. Regional air quality in Southeast Asia has been seasonally affected by the transboundary haze problem, which has often been the result of forest fires from "slash-and-burn" farming methods. In light of growing public health concerns, recent studies have begun to examine the health effects of this seasonal haze problem in Southeast Asia. This review paper aims to synthesize current research efforts on the impact of the Southeast Asian transboundary haze on acute aspects of public health. Existing studies conducted in countries affected by transboundary haze indicate consistent links between haze exposure and acute psychological, respiratory, cardiovascular, and neurological morbidity and mortality. Future prospective and longitudinal studies are warranted to quantify the long-term health effects of recurrent, but intermittent, exposure to high levels of seasonal haze. The mechanism, toxicology and pathophysiology by which these toxic particles contribute to disease and mortality should be further investigated. Epidemiological studies on the disease burden and socioeconomic cost of haze exposure would also be useful to guide policy-making and international strategy in minimizing the impact of seasonal haze in Southeast Asia.

Canadian harm reduction policies: A comparative content analysis of provincial and territorial documents, 2000-2015.

BACKGROUND: Access to harm reduction interventions among substance users across Canada is highly variable, and largely within the policy jurisdiction of the provinces and territories. This study systematically described variation in policy frameworks guiding harm reduction services among Canadian provinces and territories as part of the first national multimethod case study of harm reduction policy. METHODS: Systematic and purposive searches identified publicly-accessible policy texts guiding planning and organization of one or more of seven targeted harm reduction services: needle distribution, naloxone, supervised injection/consumption, low-threshold opioid substitution (or maintenance) treatment, buprenorphine/naloxone (suboxone), drug checking, and safer inhalation kits. A corpus of 101 documents written or commissioned by provincial/territorial governments or their regional health authorities from 2000 to 2015 were identified and verified for relevance by a National Reference Committee. Texts were content analyzed using an a priori governance framework assessing managerial roles and functions, structures, interventions endorsed, client characteristics, and environmental variables. RESULTS: Nationally, few (12%) of the documents were written to expressly guide harm reduction services or resources as their primary named purpose; most documents included harm reduction as a component of broader addiction and/or mental health strategies (43%) or blood-borne pathogen strategies (43%). Most documents (72%) identified roles and responsibilities of health service providers, but fewer declared how services would be funded (56%), specified a policy timeline (38%), referenced supporting legislation (26%), or received endorsement from elected members of government (16%). Nonspecific references to 'harm reduction' appeared an average of 12.8 times per document-far more frequently than references to specific harm reduction interventions (needle distribution=4.6 times/document; supervised injection service=1.4 times/document). Low-threshold opioid substitution, safer inhalation kits, drug checking, and buprenorphine/naloxone were virtually unmentioned. Two cases (Quebec and BC) produced about half of all policy documents, while 6 cases - covering parts of Atlantic and Northern Canada - each produced three or fewer. CONCLUSION: Canada exhibited wide regional variation in policies guiding the planning and organization of Canadian harm reduction services, with some areas of the country producing few or no policies. Despite a wealth of effectiveness and health economic research demonstrating the value of specific harm reduction interventions, policies guiding Canada from 2000 to 2015 did not stake out harm reduction interventions as a distinct, legitimate health service domain.

Quality of Life Outcomes From a Phase 2 Trial of Short-Course Radiation Therapy Followed by FOLFOX Chemotherapy as Preoperative Treatment for Rectal Cancer.

PURPOSE: A prospective phase 2 trial of short-course (SC) radiation therapy (RT) with 25 Gy over 5 fractions, followed by 4 cycles of 5-fluorouracil, oxaliplatin, and leucovorin (mFOLFOX6) before surgery was recently completed at our institution. We present here the patient-reported quality of life (QOL) outcomes from this trial. METHODS AND MATERIALS: Eighty patients with cT3/T4, any N, any M rectal adenocarcinoma planned for resection were enrolled between 2009 and 2012. The QOL data were obtained prospectively using the Functional Assessment of Cancer Therapy-Colon (FACT-C) questionnaire before RT, before surgery, and 1 year after surgery. The previously validated minimally importance difference (MID) method was used to measure clinically significant QOL changes in FACT-C scores for each patient across time points. We examined the role of ostomy on QOL. We also compared QOL with disease outcomes and physician-reported toxicity. RESULTS: The FACT-C questionnaire was completed by 97% of patients before RT, 85% immediately before surgery, and 62% 1 year after surgery. There was no statistically significant change in mean FACT-C scores from before treatment to after treatment. The majority of patients had either no change or an increase in QOL 1 year after treatment using the MID method. There were significant changes in QOL between patients with ostomy versus no ostomy 1 year after treatment for functional well-being (FWB) (14.81 vs 20.52, P=.018) and the colorectal cancer subscale (CCS) using the MID method (P=.004). Patients without ostomy reported stable changes in bowel control 1 year after surgery. There was no statistically significant correlation between QOL and disease recurrence, pathologic complete response, pathologic T stage downstaging, or acute/late toxicity. CONCLUSIONS: SC-RT and sequential mFOLFOX6 as preoperative therapy for rectal cancer results in stable patient-reported QOL outcomes 1 year after treatment. These findings in conjunction with previously reported oncologic outcomes support further evaluation of this regimen in a phase 3 setting.