Accuracy of blood-based biomarkers for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline.

BACKGROUND AND AIMS: Blood-based biomarkers have been proposed as an alternative to liver biopsy for non-invasive liver disease assessment (NILDA) in chronic liver disease (CLD). Our aims for this systematic review were to evaluate the diagnostic utility of selected blood-based tests either alone, or in combination, for identifying significant fibrosis (F2-4), advanced fibrosis (F3-4) and cirrhosis (F4), as compared to biopsy in CLD. APPROACH AND RESULTS: We included a comprehensive search of databases including Ovid MEDLINE(R), EMBASE, Cochrane Database, and Scopus through to April 2022. Two independent reviewers selected 286 studies with 103,162 patients. The most frequently identified studies included the simple aminotransferase-to-platelet ratio index (APRI) and fibrosis (FIB)-4 markers (with low-to-moderate risk of bias) in hepatitis B virus (HBV) and C virus (HCV), HIV-HCV/HBV co-infection, and nonalcoholic fatty liver disease (NAFLD). Positive (LR+) and negative (LR) likelihood ratios across direct and indirect biomarker tests for HCV and HBV for F2-4, F3-4, or F4 were 1.66-6.25 and 0.23-0.80, 1.89-5.24 and 0.12-0.64, and 1.32-7.15 and 0.15-0.86 respectively; LR+ and LR for NAFLD F2-4, F3-4 and F4 were 2-65-3.37 and 0.37-0.39, 2.25-6.76 and 0.07-0.87, and 3.90 and 0.15 respectively. Overall, proportional odds ratio indicated FIB-4 <1.45 was better than APRI <0.5 for F2-4. FIB-4 >3.25 was also better than APRI >1.5 for F3-4 and F4. There was limited data for combined tests. CONCLUSIONS: Blood-based biomarkers are associated with small-to-moderate change in pre-test probability for diagnosing F2-4, F3-4, and F4 in viral hepatitis, HIV-HCV co-infection, and NAFLD, with limited comparative or combination studies for other CLD.

Different meta-analysis methods can change judgements about imprecision of effect estimates: a meta-epidemiological study.

OBJECTIVES: To empirically evaluate five commonly used meta-analysis methods and their impact on imprecision judgements about effect estimates. The two fixed-effect model methods were the inverse variance method based on normal distribution and the Mantel-Haenszel method. The three random-effects model methods were the DerSimonian and Laird, the Hartung-Knapp-Sidik-Jonkman and the profile likelihood approaches. DESIGN: Meta-epidemiological study. SETTING: Meta-analyses published between 2007 and 2019 in the 10 general medical journals with the highest impact factors that evaluated a medication or device for chronic medical conditions and included at least 5 randomised trials. MAIN OUTCOME MEASURES: Discordance in the judgements of imprecision of effect estimates based on two definitions: when either boundary of 95% CI of the OR changed by more than 15% or changed in relation to the null. RESULTS: We analysed 88 meta-analyses including 1114 trials with an average of 12.60 trials per meta-analysis and average I2 of 26% (range: 0%-96%). The profile likelihood failed to converge in three meta-analyses (3%). Discordance in imprecision judgements based on the two definitions, respectively, occurred between the fixed normal distribution and fixed Mantel-Haenszel method (8% and 2%), between the DerSimonian and Laird and Hartung-Knapp-Sidik-Jonkman methods (19% and 10%), between the DerSimonian and Laird and profile likelihood methods (9% and 5%), and between the Hartung-Knapp-Sidik-Jonkman and profile likelihood methods (5% and 13%). Discordance was greater when fewer studies and greater heterogeneity was present. CONCLUSION: Empirical evaluation of studies of chronic medical conditions showed that conclusions about the precision of the estimates of the efficacy of a drug or device frequently changed when different pooling methods were used, particularly when the number of studies within a meta-analysis was small and statistical heterogeneity was substantial. Sensitivity analyses using more than one method may need to be considered in these two scenarios.

A systematic review and meta-analysis of treatment and natural history of popliteal artery aneurysms.

OBJECTIVE: To summarize the best available evidence comparing open vs endovascular popliteal artery aneurysm (PAA) repair. We also summarized the natural history of PAAs to support of the Society for Vascular Surgery guidelines. METHODS: We searched MEDLINE, EMBASE, Cochrane databases, and Scopus for studies of patients with PAAs treated with an open vs an endovascular approach. We also included studies of natural history of untreated patients. Studies were selected and appraised by pairs of independent reviewers. A meta-analysis was performed when appropriate. RESULTS: We identified 32 original studies and 4 systematic reviews from 2191 candidate references. Meta-analysis showed that compared with the endovascular approach, open surgical repair was associated with higher primary patency at 1 year (odds ratio [OR], 2.10; 95% confidence interval [CI], 1.41-3.12), lower occlusion rate at 30 days (OR, 0.41; 95% CI, 0.24-0.68) and fewer reinterventions (OR, 0.28; 95% CI, 0.17-0.45), but a longer hospital stay (standardized mean difference, 2.16; 95% CI, 1.23-3.09) and more wound complications (OR, 5.18; 95% CI, 2.19-12.26). There was no statistically significant difference in primary patency at 3 years (OR, 1.38; 95% CI, 0.97-1.97), secondary patency (OR, 1.59; 95% CI, 0.84-3.03), mortality at the longest follow-up (OR, 0.49; 95% CI, 0.21-1.17), mortality at 30 days (OR, 0.28; 95% CI, 0.06-1.36), or amputation (incidence rate ratio, 0.85; 95% CI, 0.56-1.31). The certainty in these estimates was, in general, low. Studies of PAA natural history suggest that thromboembolic complications and amputation develop at a mean observation time of 18 months and they are frequent. One study showed that at 5 years, approximately one-half of the patients had complications. CONCLUSIONS: This systematic review provides event rates for outcomes important to patients with PAAs. Despite the low certainty of the evidence, these rates along with surgical expertise and anatomic feasibility can help patients and surgeons to engage in shared decision-making.

Risk Factors for Premature Myocardial Infarction: A Systematic Review and Meta-analysis of 77 Studies.

OBJECTIVE: To evaluate the magnitude of the association between risk factors and premature myocardial infarction (MI) (men aged 18-55 years; women aged 18-65 years). PATIENTS AND METHODS: We searched MEDLINE and other databases from inception through April 30, 2020, as well as bibliography of articles selected for data extraction. We selected observational studies reporting the magnitude of the association of at least 1 risk factor (demographic characteristics, lifestyle factors, clinical risk factors, or biomarkers) with premature MI and a control group. Pooled risk estimates (random effects) from all studies unadjusted and adjusted for risk factors were reported as summary odds ratios (ORs) with 95% CIs. RESULTS: From 35,320 articles of 12.7 million participants, we extracted data on 19 risk factors from 77 studies across 58 countries. Men had a higher risk of premature MI (OR, 2.39; 95% CI, 1.71 to 3.35) than did women. Family history of cardiac disease was associated with a higher risk of premature MI (OR, 2.67; 95% CI, 2.29 to 3.27). Major modifiable risk factors associated with higher risk were current smoking (OR, 4.34; 95% CI, 3.68 to 5.12 vs no/former), diabetes mellitus (OR, 3.54; 95% CI, 2.69 to 4.65), dyslipidemia (OR, 2.94; 95% CI, 1.76 to 4.91), and hypertension (OR, 2.85; 95% CI, 2.48 to 3.27). Higher body mass index carried higher risk (OR, 1.46; 95% CI, 1.24 to 1.71 for ≥25 kg/m2 vs <25 kg/m2). Biomarkers associated with 2- to 3-fold higher risk were total cholesterol levels greater than 200 mg/dL, triglyceride levels higher than 150 mg/dL, and high-density lipoprotein cholesterol levels less than 60 mg/dL (to convert to mmol/L, multiply by 0.0259). CONCLUSION: Major risk factors for premature MI are mostly amenable to patient, population, and policy level interventions. Mild elevations in body mass index and triglyceride levels were associated with higher risk, which has implications for the growing worldwide epidemic of cardiometabolic diseases.

Carotid plaque vulnerability on magnetic resonance imaging and risk of future ischemic events: a systematic review and meta-analysis.

INTRODUCTION: Magnetic resonance imaging (MRI) can characterize carotid plaque features, including intraplaque hemorrhage (IPH), lipid-rich necrotic core (LRNC), and thin/ruptured fibrous cap (TRFC), that have increased tendency to cause future cerebrovascular ischemic events. We performed a systematic review and meta-analysis of studies evaluating association of MRI-identified high-risk plaque features, including IPH, LRNC, and TRFC, with risks of subsequent ischemic events of stroke, transient ischemic attack (TIA), or amaurosis fugax (AF) over follow-up duration of ≥3 months. EVIDENCE ACQUISITION: Multiple databases were searched for relevant publications between January 2000 and March 2020. Studies reporting outcomes of future ischemic events of stroke, TIA, or AF for individual MRI-identified high-risk carotid plaque features over follow-up duration of ≥3 months were included. Random effects meta-analysis was performed to estimate odds ratios (OR) and 95% confidence intervals (CI) comparing outcomes between MRI-positive and MRI-negative groups. EVIDENCE SYNTHESIS: Fifteen studies including 2350 patients were included. The annual rate of future ischemic events was 11.9% for MRI-positive IPH, 5.4% for LRNC, and 5.7% for TRFC. IPH, LRNC, and TRFC were associated with increased risk of future ischemic events (OR 6.37; 95% CI, 3.96 to 10.24), (OR 4.34; 95% CI, 1.65 to 11.42), and (OR 10.60, 95% CI 3.56 to 31.58), respectively. CONCLUSIONS: The current study findings strengthen the assertion that MRI-positive "high-risk" or "vulnerable" plaque features, including IPH, LRNC, and/or TRFC can predict risks of future ischemic events of stroke, TIA, or AF.

Weight Loss and Serum Lipids in Overweight and Obese Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: Excess adipose tissue is associated with an abnormal lipid profile that may improve with weight reduction. In this meta-analysis, we aimed to estimate the magnitude of change in lipid parameters associated with weight loss in adults who are overweight or obese. METHODS: We searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Scopus from 2013 to September, 2018. We included randomized controlled trials (RCTs) that evaluated interventions to treat adult obesity (lifestyle, pharmacologic and surgical) with follow-up of 6 months or more. RESULTS: We included 73 RCTs with moderate-to-low risk of bias, enrolling 32 496 patients (mean age, 48.1 years; weight, 101.6 kg; and body mass index [BMI], 36.3 kg/m2). Lifestyle interventions (diet, exercise, or both), pharmacotherapy, and bariatric surgery were associated with reduced triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) concentrations and increased high-density lipoprotein cholesterol (HDL-C) at 6 and 12 months. The following data are for changes in lipid parameters after 12 months of the intervention with 95% CI. Following lifestyle interventions, per 1 kg of weight lost, TGs were reduced by -4.0 mg/dL (95% CI, -5.24 to -2.77 mg/dL), LDL-C was reduced by -1.28 mg/dL (95% CI, -2.19 to -0.37 mg/dL), and HDL-C increased by 0.46 mg/dL (95% CI, 0.20 to 0.71 mg/dL). Following pharmacologic interventions, per 1 kg of weight lost, TGs were reduced by -1.25 mg/dL (95% CI, -2.94 to 0.43 mg/dL), LDL-C was reduced by -1.67 mg/dL (95% CI, -2.28 to -1.06 mg/dL), and HDL-C increased by 0.37 mg/dL (95% CI, 0.23 to 0.52 mg/dL). Following bariatric surgery, per 1 kg of weight lost, TGs were reduced by -2.47 mg/dL (95% CI, -3.14 to -1.80 mg/dL), LDL-C was reduced by -0.33 mg/dL (95% CI, -0.77 to 0.10 mg/dL), and HDL-C increased by 0.42 mg/dL (95% CI, 0.37 to 0.47 mg/dL). Low-carbohydrate diets resulted in reductions in TGs and increases in HDL-C, whereas low-fat diets resulted in reductions in TGs and LDL-C and increases in HDL-C. Results were consistent across malabsorptive and restrictive surgery. CONCLUSIONS: Weight loss in adults is associated with statistically significant changes in serum lipids. The reported magnitude of improvement can help in setting expectations, inform shared decision making, and facilitate counseling.

Effect of Ketamine/Propofol Admixture on Peri-Induction Hemodynamics: A Systematic Review and Meta-Analysis.

To evaluate the effectiveness of an admixture of ketamine and propofol on peri-induction hemodynamics during airway manipulation, we searched electronic databases of randomized controlled trials from January 1, 2000, to October 17, 2018. Trial screening, selection, and data extraction were done independently by two reviewers with outcomes pooled across included trials using the random-effects model. We included 10 randomized trials (722 patients, mean age of 53.99 years, 39.96% female). American Society of Anesthesiologists physical status was reported in 9 trials with classes I and II representing the majority. Ketamine/propofol admixture was associated with a nonsignificant increase in heart rate (weighted mean difference, 3.36 beats per minute (95% CI, -0.88, 7.60), I 2 = 88.6%), a statistically significant increase in systolic blood pressure (weighted mean difference, 9.67 mmHg (95% CI, 1.48, 17.86), I 2 = 87.2%), a nonsignificant increase in diastolic blood pressure (weighted mean difference, 2.18 mmHg (95% CI, -2.82, 7.19), I 2 = 73.1%), and a nonsignificant increase in mean arterial pressure (weighted mean difference, 3.28 mmHg (95% CI, -0.94, 7.49), I 2 = 69.9%) compared to other agents. The risk of bias was high and the certainty of evidence was low. In conclusion, among patients undergoing airway manipulation and needing sedation, the use of a ketamine/propofol admixture may be associated with better hemodynamics compared to nonketamine/propofol sedation. This trial is registered with CRD42019125725.

Aspirin dosage for the prevention of graft occlusion in people undergoing coronary surgery: A systematic review and meta-analysis.

BACKGROUND: Aspirin is almost always used after coronary artery bypass graft (CABG) surgery; however, it is unclear what optimal dose should be prescribed. In this systematic review, we evaluated the effects of high versus low-dose aspirin in patients after CABG. METHODS: A comprehensive database search was conducted in several databases from date of inception until February 2018. There were no language restrictions. We included studies that compared different doses of aspirin in patients that had undergone CABG surgery. We included studies that evaluated patient-important outcomes (mortality, cardiovascular events, and gastrointestinal bleeding); and if not reported, we collected data on the surrogate outcome thromboxane B2 (TXB2). We collected relevant data and performed a meta-analysis. RESULTS: We identified 5903 references, and after two levels of screening by two independent reviewers, we included three randomized controlled trials in the meta-analysis with a total number of 122 participants. Mean age of trial participants was 65.63 years, and 88.68% were male. We planned to analyze all possible clinical outcomes, including mortality, recurrence, and hospitalization. However, no clinical outcomes are reported by the literature. The surrogate biochemical outcome of serum TXB2 was the only outcome reported by the eligible studies. High-dose aspirin (162-325mg once daily) achieved better suppression of TXB2 than low-dose aspirin (75-100mg once daily) (mean difference [MD], 2.00ng/mL, 95% confidence interval [CI]: 0.72-3.32; participants = 122; studies = 3; I2 = 0%). CONCLUSIONS: We found no clinical trials addressing any of the clinical outcomes of interest. High-dose aspirin was superior to low-dose aspirin in suppressing platelet function, a surrogate outcome. Trials evaluating clinical and patient-important outcomes are needed to better inform medical practice and fill this gap in clinical knowledge.

Correlation of MRI-detected vulnerable carotid plaques with clinical presentation: a systematic review and meta-analysis.

INTRODUCTION: To determine the association between magnetic resonance imaging (MRI)-detected vulnerable Carotid Plaques and clinical presentation related to ipsilateral carotid artery territory. EVIDENCE ACQUISITION: We searched three databases including Ovid MEDLINE, Ovid EMBASE, and Scopus from 2000 to 2018 for studies that evaluated vulnerable carotid plaques by MRI defined as intraplaque hemorrhage (IPH), lipid-rich necrotic core (LRNC), or thinning/rupture of the fibrous cap (TRFC). Data on study characteristics, clinical presentation, and MRI findings were extracted. Publication bias, methodologic quality, and study heterogeneity were assessed. Random-effects meta-analysis model was used to estimate incidence rate ratio (IRR) and 95% confidence intervals (CI) of MRI-detected vulnerable carotid plaque between symptomatic and asymptomatic arteries. EVIDENCE SYNTHESIS: Of 2855 studies, 33 studies containing 6210 participants with 8401 assessed arteries were included. Overall, the risk of bias was moderate in 13, and low in 20 studies. The prevalence of MRI-positive IPH, TRFC, and LRNC were higher in symptomatic groups compared with the asymptomatic groups. In 11 studies that compared vulnerable carotid plaques between symptomatic and asymptomatic groups, symptomatic presentation was correlated with increased risk of IPH (IRR=1.57; 95% CI: 1.24-1.99), TRFC (IRR=2.26; 95% CI: 1.83 to 3.76), and LRNC (IRR=1.95; 95% CI: 1.28 to 2.97), respectively. CONCLUSIONS: The presence of MRI-positive vulnerable carotid plaques including IPH, LRNC, and TRFC is positively associated with symptomatic clinical presentation. Therefore, carotid plaque MRI might be a useful risk stratification tool in determining the risk of ischemic stroke.

Submaximal angioplasty in the treatment of patients with symptomatic ICAD: a systematic review and meta-analysis.

INTRODUCTION: Management approaches for intracranial atherosclerosis include medical, surgical, or endovascular treatment. Among endovascular treatments, recent studies have stated that submaximal angioplasty (SA) may offer considerable benefits and be a promising alternative to aggressive medical therapyand/or stenting in the treatment of intracranial atherosclerotic disease (ICAD). OBJECTIVE: To investigate the rates of periprocedural and long-term cerebrovascular accidents, mortality, and restenosis in patients with symptomatic ICAD who were treated with SA. METHODS: An electronic database search was performed for relevant studies that reported clinical outcomes of patients with ICAD following SA. Outcomes of interest were incidence of transient ischemic attack, intracerebral hemorrhage, stroke, and mortality in the periprocedural period and at 1 year. The periprocedural period was defined as the time from SA until 30 days after the procedure. Technical success and restenosis rates after the procedure were also analyzed. RESULTS: A total of 19 studies with 777 patients were identified. The technical success rate was 93% (95% CI 85% to 98%). The incidence of 30-day and 1-year stroke (all types) was 3% (95% CI 1% to 5%) and 5% (95% CI 4% to 8%), respectively. Thirty-day and 1-year mortality was found to be 1% (95% CI 0% to 2%) and 2% (95% CI 0% to 4%), respectively. The combined incidence of stroke or death was 5% (95% CI 3% to 8%) at 30 days, and 9% (95% CI 7% to 12%) at 1 year. CONCLUSION: The findings suggest that SA might be a promising alternative treatment in the treatment of symptomatic ICAD due to its favorable technical profile, periprocedural safety, and long-term efficacy. A randomized clinical trial is warranted to compare the safety and efficacy of SA with 'gold standard' medical treatment.

Prior malignancy impact on survival outcomes of glioblastoma multiforme; population-based study.

BACKGROUND: Glioblastoma multiforme (GBM) patients with a prior malignancy are usually excluded from clinical trials on GBM based on the assumption that this history will affect their survival outcomes. This practice may affect clinical trial accrual and limit the gathering of knowledge essential to the formulation of therapeutic options for this patient population. However, not much is known about the real impact of these prior malignancies on the survival of patients with subsequent GBM. We aimed to investigate the degree of such an impact. PATIENTS AND METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) Program to analyze data of GBM patients diagnosed between 1973 and 2014. We calculated the overall and GBM-specific survival of these patients using the unadjusted Kaplan-Meier test and the multivariable covariate-adjusted Cox models. RESULTS: Of 51,158 GBM patients, 3,076 had a prior malignancy. The unadjusted Kaplan-Meier test showed worse overall and GBM-specific survivals for patients who had a prior history of cancer. However, after adjusting for age at diagnosis of GBM, sex, race, marital status, and conduction of surgery, multivariable covariate-adjusted Cox models showed that having a prior malignancy did not significantly affect neither overall survival (HR = 1.025, 95%CI = .986 - 1.066, p = .213) nor GBM-specific survival (HR = 1.005, 95%CI = .963 - 1.049, p = .810). CONCLUSIONS: Our findings suggest that the broad practice of excluding patients with a prior history of cancer should be reconsidered as it may adversely affect accrual, trial completion rates, and generalizability of the results.

Surgical anatomy, radiological features, and molecular biology of the lumbar intervertebral discs.

The intervertebral disc (IVD) is a joint unique in structure and functions. Lying between adjacent vertebrae, it provides both the primary support and the elasticity required for the spine to move stably. Various aspects of the IVD have long been studied by researchers seeking a better understanding of its dynamics, aging, and subsequent disorders. In this article, we review the surgical anatomy, imaging modalities, and molecular biology of the lumbar IVD. Clin. Anat. 30:251-266, 2017. © 2017 Wiley Periodicals, Inc.

An unusual cause of cerebellovestibular symptoms.

Hashimoto encephalopathy (HE) is a controversial autoimmune disorder, probably underdiagnosed, that causes a wide variety of neurological manifestations. Symptoms differ among patients and may be very severe in some cases. However, it can be treated, with a very good prognosis. In our case, a teenaged girl with a family history of migraine, vitiligo and benign paroxysmal positional vertigo presented with severe ataxia, vomiting and hypotension. She had a history of similar, but milder, symptoms and was misdiagnosed several times. She had subclinical hypothyroidism, and high levels of antithyroid antibodies. There were abnormal MRI and visual evoked potential findings. After excluding other more common causes, we diagnosed her as having 'Hashimoto Encephalopathy', and started treatment with corticosteroids, on which she showed dramatic improvement. After about 2 years of presentation, the patient is able to continue her life independently.