Non-invasive liver disease assessment to identify portal hypertension: A systematic review supporting the AASLD Practice Guideline.

INTRODUCTION: Portal hypertension is a serious complication of cirrhosis, which leads to life-threatening complications. Hepatic venous pressure gradient (HVPG), a surrogate of portal pressure, is the reference standard test to assess the severity of portal hypertension. However, since HVPG is limited by its invasiveness and by its availability, non-invasive liver disease assessments (NILDAs) to assess portal pressure, especially clinically significant portal hypertension (CSPH), are needed. METHODS: We conducted a systematic review of Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus from each database's inception to April 22 nd , 2022. We included only studies in English that examined ≥50 patients in single liver disease etiologies which compared non-invasive tests (blood, and/or imaging) to HVPG for predicting clinically significant portal hypertension (CSPH; defined as HVPG ≥10 mm Hg) in patients with chronic liver disease (this therefore limited the number of studies that could be included). Outcomes reported included measures of diagnostic test accuracy. Additionally, a narrative review of studies not eligible for the systematic review is also provided. RESULTS: Nine studies with 2,492 patients met the inclusion criteria. There was substantial heterogeneity with regard to liver disease studied and cutoff values used to detect CSPH. Blood based tests, including aspartate to platelet ratio index (APRI) (56% sensitivity and 68% specificity) and fibrosis-4 (FIB-4) (54% sensitivity and 73% specificity) had low accuracy measures. Imaging based tests (transient elastography (TE) and shear wave elastography detection of liver stiffness (LSM)) had better accuracy, but also had substantial variation; at 15 kPa, TE sensitivity was 90%-96% and specificity was 48%-50% while at 25 kPa, its sensitivity and specificity were 57%-85% and 82%-93%, respectively. The narrative review suggested that imaging based tests are the best available NILDA to detect CSPH, CSPH is highly unlikely to be present at an LSM ≤15 kPa and likely to be present at an LSM ≥25 kPa. CONCLUSION: While imaging-based NILDA appeared to have higher accuracy than blood-based tests to detect CSPH, only 9 studies fit the a priori established inclusion criteria for the SR. In addition, there was substantial study heterogeneity and variation in cutoffs for LSM to detect CSPH, limiting the ability to establish definitive cutoffs to detect CSPH.

Imaging-based non-invasive liver disease assessment for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline.

BACKGROUND AND AIMS: Transient elastography (TE), shear-wave elastography (SWE), and/or magnetic resonance elastography (MRE), each providing liver stiffness measurement (LSM), are the most studied imaging-based noninvasive liver disease assessment (NILDA) techniques. To support the American Association for the Study of Liver Diseases guidelines on NILDA, we summarized the evidence on the accuracy of these LSM methods to stage liver fibrosis (F). APPROACH AND RESULTS: A comprehensive search for studies assessing LSM by TE, SWE, or MRE for the identification of significant fibrosis (F2-4), advanced fibrosis (F3-4), or cirrhosis (F4), utilizing histopathology as standard of reference by liver disease etiology in adults or children from inception to April 2022 was performed. We excluded studies with <50 patients with a single disease entity and mixed liver disease etiologies (with the exception of HCV/HIV co-infection). Out of 9447 studies, 240 with 61,193 patients were included in this systematic review. In adults, sensitivities for the identification of F2-4 ranged from 51% to 95%, for F3-4 from 70% to 100%, and for F4 from 60% to 100% across all techniques/diseases, whereas specificities ranged from 36% to 100%, 74% to 100%, and 67% to 99%, respectively. The largest body of evidence available was for TE; MRE appeared to be the most accurate method. Imaging-based NILDA outperformed blood-based NILDA in most comparisons, particularly for the identification of F3-4/F4. In the pediatric population, imaging-based NILDA is likely as accurate as in adults. CONCLUSION: LSM from TE, SWE, and MRE show acceptable to outstanding accuracy for the detection of liver fibrosis across various liver disease etiologies. Accuracy increased from F2-4 to F3-4 and was the highest for F4. Further research is needed to better standardize the use of imaging-based NILDA, particularly in pediatric liver diseases.

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.

Using the daily rate of rise in hemoglobin S to manage RBC depletion/exchange treatment in sickle cell disease.

BACKGROUND: Red blood cell exchange is often used prophylactically in patients with sickle cell disease, with the goal to maintain hemoglobin S (HbS) below a target threshold level. We reviewed whether the daily "rate of rise" (RoR) in HbS that occurs between procedures can be used for patient management. For some patients not achieving their HbS goals despite efficient exchanges, the post-procedure hematocrit (Hct) target is increased to potentially suppress HbS production. This case series explores the utility of this approach, other clinical uses of the daily RoR in HbS, and the factors that influence it. STUDY DESIGN AND METHODS: A total of 660 procedures from 24 patients undergoing prophylactic RBC depletion/exchange procedures were included. Laboratory values and clinical parameters were collected and used to calculate the daily RoR in HbS. Factors such as Hct or medications that might influence the RoR in HbS were evaluated. RESULTS: The RoR in HbS varied widely between patients but remained relatively stable within individuals. Surprisingly, this value was not significantly influenced by changes in post-procedure Hct or concurrent hydroxyurea use. A patient's average RoR in HbS effectively predicted the pre-procedure HbS at the following visit (R2 = 0.65). DISCUSSION: The RoR in HbS is a relatively consistent parameter for individual patients that is unaffected by medication use or procedural Hct targets and may be useful in determining intervals between procedures.

Assessment of specificity of dermatopathologic criteria for IgG4-related skin disease.

BACKGROUND: IgG4-related disease (IgG4-RD) represents a recently characterized multisystemic fibroinflammatory condition that can manifest a spectrum of skin findings (IgG4-related skin disease; IgG4-RSD). Histopathologic and immunohistochemical criteria have been proposed; however, the specificity of these criteria merits scrutiny given the potential histopathologic overlap of IgG4-RSD and both neoplastic and inflammatory skin conditions featuring lymphoplasmacytic infiltrates (IgG4-RSD mimics). This study sought to assess the specificity of the criteria by quantifying the frequency by which an expanded spectrum of IgG4-RSD mimics meet proposed thresholds. METHODS: Following IRB approval, a total of 69 cases of IgG4-RD mimics, representing 14 different diagnoses featuring plasma cells, were reviewed and analyzed for the following histopathologic and immunohistochemical features: (i) maximum IgG4+ count/high-powered field (hpf) >200; (ii) IgG4/IgG ratio >0.4 averaged over 3 hpfs; (iii) IgG4+ count >10 per hpf. RESULTS: Screening for IgG4-RSD by histopathologic criteria demonstrated the high frequency of lymphoplasmacytic infiltrates, contrasted with the rarity of storiform fibrosis (only one case of erythema elevatum diutinum [EED]) and obliterative phlebitis (0 cases). By immunohistochemical criteria, the analysis revealed that no cases exceeded 200 IgG4+ cells; 13% (9/69) cases demonstrated an IgG4/IgG ratio of >0.4 averaged over 3 hpfs; and 23% (16/69) cases demonstrated a mean IgG4+ count of >10 per hpf. CONCLUSION: Application of proposed IgG4-RSD histopathologic criteria to an expanded spectrum of potential IgG4-RSD mimics (to include cutaneous marginal zone lymphoma, syphilis, necrobiosis lipoidica, lichen sclerosus, ALHE, psoriasis, lymphoplasmacytic plaque, EED, and erosive pustular dermatosis), highlights the relative nonspecificity of lymphoplasmacytic infiltrates contrasted with the stringency of storiform fibrosis and obliterative fibrosis. Furthermore, an IgG4+ cell count of >10 per hpf and an IgG4/IgG ratio of >0.4 are not specific to IgG4-RSD alone. In the appropriate clinical context for IgG4-RSD, histopathologic features still represent the entry threshold for diagnosis consideration, which then allows for further screening by immunohistochemical criteria.

Induction and maintenance of remission with mycophenolate mofetil in ANCA-associated vasculitis: a systematic review and meta-analysis.

BACKGROUND: Uncertainties exist about the use of mycophenolate mofetil (MMF) in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV), particularly for remission maintenance. METHODS: Systematic review and meta-analysis of phase II and III trials assessing the use of MMF in AAV, granulomatosis with polyangiitis and microscopic polyangiitis (MPA). A comprehensive search of several databases (Medline, EMBASE, Cochrane, Web of Science, Scopus) from inception to 5 May 2020 has been conducted. Trial data were extracted to estimate odds ratios (ORs) and estimates (ES) for MMF efficacy (remission-induction and maintenance). Severe adverse effects (SAEs) were collected. RESULTS: From 565 articles captured, 10 met the predefined criteria, 5 phase II and 5 III trials; 4 assessed remission-induction, 3 remission maintenance and 3 both. The pooled OR for remission-induction at 6 months was 1.06 (95% confidence interval 0.74, 1.52), with no significant difference by subgroup meta-analysis of trials stratified by different study-level features (i.e. kidney disease, MPA, myeloperoxidase-ANCA positivity, newly diagnosed disease) (P > 0.05). The overall ES for remission maintenance at the end of follow-up ranged between 51% and 91% (I2 = 74.8%). Subgroup meta-analysis identified kidney involvement as a possible source of heterogeneity, yielding a significantly higher rate of sustained remission in trials enrolling only patients with kidney involvement (92%, 76-100%) versus those enrolling patients with and without kidney involvement (56%, 45-66%). Results were similar in multiple sensitivity analyses. During follow-up, the frequency of SAEs in MMF-based treatment arms was 31.8%. CONCLUSIONS: In AAV, MMF use was significantly associated with higher sustained remission rates in trials enrolling only patients with kidney involvement. These findings might influence clinical practice.

Clinicopathologic Features of Facial Dermatofibromas, a Cohort Study, and a Systematic Review of Literature.

BACKGROUND: Dermatofibromas are common skin tumors that typically occur on the extremities and trunk and demonstrate benign behavior, frequent recurrences, and very rare metastasis. Facial dermatofibromas are rare and not well studied . We analyzed clinicopathologic features of facial dermatofibromas. DESIGN: Considering the rarity of the condition, we conducted a cohort study and a systematic review. We queried medical records of a single tertiary care center for dermatofibromas from January 1, 2000, to July 1, 2021. A systematic review of multiple databases was conducted through October 27, 2021, to include studies reporting facial dermatofibromas. Random-effects meta-analysis was used to estimate pooled odds ratio and proportions with associated 95% confidence interval (CI). RESULTS: The cohort study identified 2858 cases of dermatofibromas, of which, 23 cases from 18 patients were on the face (1%). The mean age was 52.7 ± 17.8 years. Fifty-six percent of the cases were women. The most common location was the forehead (6 cases). The mean follow-up was 54 months. Forty-four percent of the cases had subcutaneous involvement, and 39% were the cellular type. Margins were positive in 89% of the cases, recurrence rate was 22%, and no metastases were observed. The systematic review included 10 studies (119 patients). Meta-analyses showed that facial dermatofibromas were 2% of all dermatofibromas (95% CI: 1%-3%). The local recurrence rate was 14% (95% CI: 6%-26%). Facial dermatofibromas with subcutaneous involvement were more likely to recur [odds ratio 4.53 (95% CI: 1.12-18.24)]. Before histopathologic examination, clinical differential diagnosis included dermatofibromas in only 9% of the cases (95% CI: 2%-19%). CONCLUSION: Facial dermatofibromas are rare and are difficult to fully excise. Cellular type and subcutaneous or muscular involvement are common in these cases and tend to have higher local recurrence rate than other nonfacial dermatofibromas. Wider excisions might be necessary for complete excision.

A systematic review of adherence to physical activity interventions in individuals with type 2 diabetes.

Lifestyle interventions are pivotal for successful management of type 2 diabetes (T2D), however, the proportion of people with T2D adhering to physical activity advice has not been thoroughly studied. The purpose of this systematic review was to summarise the evidence on adherence to exercise or physical activity components in lifestyle interventions in those with T2D. We searched MEDLINE EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Scopus on 12 November 2019. Eligible studies enrolled adults with T2D and reported the proportion of adherence to lifestyle interventions as a primary or secondary outcome. We included 11 studies (nine randomised controlled trials (RCTs) enrolling 1717 patients and two nonrandomised studies enrolling 62 patients). Only one of the studies had low risk of bias. The proportion of participants adhering to physical activity varied from 32% to 100% with a median of 58%. Adherence was higher in interventions using supervised training and lowest in interventions using remote coaching and the adherence rate in observational studies was higher compared to RCTs (92% vs. 55%; p < 0.01). Study duration, risk of bias, or participants' sex, were not associated with adherence to physical activity. The proportion of those with T2D adhering to physical activity interventions for T2D varies widely and most of the included studies had a high risk of bias. These findings have important implications for planning and power analysis of future trials and when counselling patients about lifestyle interventions including physical activity or exercise components.

The Significance and Clinical Outcome of Lymphocytic Duodenosis in Children: Mayo Clinic Experience and Systematic Review.

BACKGROUND: Lymphocytic duodenosis (LD) defined as increased intraepithelial lymphocytes >25 intraepithelial lymphocytes (IELs) per 100 epithelial cells with normal villous architecture is associated with many gastrointestinal (GI) disorders. We aim to assess the rate and outcome of LD in children and perform a systematic review. METHOD: We reviewed all children (<18 years) who underwent esophagogastroduodenoscopy (EGD) with duodenal biopsy between January 2000 and June 2019 to identify LD cases and control group. Demographics, clinical, and pathologic information were reviewed and recorded. A systematic review including our findings was performed. RESULTS: During the study period 12,744 children underwent an EGD with biopsies. Of those, we identified 426 children with LD (3%) and 474 controls. The median age in years was 10.7 and 12.6 and there were 254 (60%) and 278 (59%) girls in the LD and control group, respectively. The most common presenting symptoms in both groups were abdominal pain (52%), gastroesophageal acid reflux disease (18%), diarrhea (16%), and vomiting (12%). Diarrhea (21% vs 12%, P < 0.001) and constipation (2% vs 0.4%, P = 0.021) were statistically different between the LD and control group, respectively. Median follow-up (range) is 3.6 (0.0, 190.9) and 3.1 (0.0, 194.2) in the LD and control group, respectively. CD (5% vs 0%, P < 0.001), Crohn disease (9% vs 3%, P = 0.003) and Helicobacter pylori gastritis (3% vs 1%, P = 0.021) were more common in the LD group. CONCLUSIONS: The Rate of LD in children is similar to reported rate in adults. In the absence of Crohn disease, CD or H. Pylori, LD seems to be a benign and transient histologic finding in children.

Eating, sleeping and sexual function disorders in women with polycystic ovary syndrome (PCOS): A systematic review and meta-analysis.

PURPOSE: We aim to evaluate the association of PCOS with eating, sleeping and sexual function disorders. METHODS: A comprehensive search including MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus through 01 August 2018 was conducted for studies reporting the prevalence of any eating, sleep or sexual function disorders in patients with PCOS. Independent reviewers selected studies and extracted data. A random-effects model was utilized to generate pooled odds ratio (OR) and 95% confidence intervals (CI) for binary outcomes, and mean difference (MD) and 95% CI for continuous outcomes. RESULTS: We included 36 studies reporting on 349,529 patients. Compared to women without PCOS, women with PCOS were more likely to have bulimia nervosa (OR 1.37; %CI, 1.17 to 1.60), binge eating (OR 2.95; 95%CI, 1.61 to 5.42), or any eating disorder (OR 1.96; 95% CI 1.18 to 3.24); but not anorexia nervosa (OR 0.92; 95%CI, 0.78 to 1.10). Women with PCOS were more likely to have sleep disorders like hypersomnia (OR 4.39; %CI, 1.07 to 18.07) and obstructive sleep apnoea (OR 10.81; %CI, 2.39 to 48.83). Women with PCOS had lower sexual satisfaction as measured on a visual analogue scale (MD -29.67; 95% CI, -36.97 to -22.37), but no difference in Total Female Sexual Function Index (MD -0.06; 95% CI, -0.51 to 0.38). CONCLUSION: PCOS can be associated with an increased risk of eating and sleeping disorders as well as decreased sexual satisfaction. Screening for these disorders in women with PCOS may allow early intervention and improve quality of life.

Improving Blood Pressure Management in Primary Care Patients with Chronic Kidney Disease: a Systematic Review of Interventions and Implementation Strategies.

INTRODUCTION: Chronic kidney disease (CKD) is widely prevalent, associated with morbidity and mortality, but may be lessened with timely implementation of evidence-based strategies including blood pressure (BP) control. Nonetheless, an evidence-practice gap persists. We synthesize the evidence for clinician-facing interventions to improve hypertension management in CKD patients in primary care. METHODS: Electronic databases and related publications were queried for relevant studies. We used a conceptual model to address heterogeneity of interventions. We conducted a quantitative synthesis of interventions on blood pressure (BP) outcomes and a narrative synthesis of other CKD relevant clinical outcomes. Planned subgroup analyses were performed by (1) study design (randomized controlled trials (RCTs) or nonrandomized studies (NRS)); (2) intervention type (guideline-concordant decision support, shared care, pharmacist-facing); and (3) use of behavioral/implementation theory. RESULTS: Of 2704 manuscripts screened, 73 underwent full-text review; 22 met inclusion criteria. BP target achievement was reported in 15 and systolic BP reduction in 6 studies. Among RCTs, all interventions had a significant effect on BP control, (pooled OR 1.21; 95% CI 1.07 to 1.38). Subgroup analysis by intervention type showed significant effects for guideline-concordant decision support (pooled OR 1.19; 95% CI 1.12 to 1.27) but not shared care (pooled OR 1.71; 95% CI 0.96 to 3.03) or pharmacist-facing interventions (pooled OR 1.04; 95% CI 0.82 to 1.34). Subgroup analysis finding was replicated with pooling of RCTs and NRS. The five contributing studies showed large and significant reduction in systolic BP (pooled WMD - 3.86; 95% CI - 7.2 to - 0.55). Use of a behavioral/implementation theory had no impact, while RCTs showed smaller effect sizes than NRS. DISCUSSION: Process-oriented implementation strategies used with guideline-concordant decision support was a promising implementation approach. Better reporting guidelines on implementation would enable more useful synthesis of the efficacy of CKD clinical interventions integrated into primary care. PROSPERO REGISTRATION NUMBER: CRD42018102441.

Association of Home Noninvasive Positive Pressure Ventilation With Clinical Outcomes in Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis.

Importance: The association of home noninvasive positive pressure ventilation (NIPPV) with outcomes in chronic obstructive pulmonary disease (COPD) and hypercapnia is uncertain. Objective: To evaluate the association of home NIPPV via bilevel positive airway pressure (BPAP) devices and noninvasive home mechanical ventilator (HMV) devices with clinical outcomes and adverse events in patients with COPD and hypercapnia. Data Sources: Search of MEDLINE, EMBASE, SCOPUS, Cochrane Central Registrar of Controlled Trials, Cochrane Database of Systematic Reviews, National Guideline Clearinghouse, and Scopus for English-language articles published from January 1, 1995, to November 6, 2019. Study Selection: Randomized clinical trials (RCTs) and comparative observational studies that enrolled adults with COPD with hypercapnia who used home NIPPV for more than 1 month were included. Data Extraction and Synthesis: Data extraction was completed by independent pairs of reviewers. Risk of bias was evaluated using the Cochrane Collaboration risk of bias tool for RCTs and select items from the Newcastle-Ottawa Scale for nonrandomized studies. Main Outcomes and Measures: Primary outcomes were mortality, all-cause hospital admissions, need for intubation, and quality of life at the longest follow-up. Results: A total of 21 RCTs and 12 observational studies evaluating 51 085 patients (mean [SD] age, 65.7 [2.1] years; 43% women) were included, among whom there were 434 deaths and 27 patients who underwent intubation. BPAP compared with no device was significantly associated with lower risk of mortality (22.31% vs 28.57%; risk difference [RD], -5.53% [95% CI, -10.29% to -0.76%]; odds ratio [OR], 0.66 [95% CI, 0.51-0.87]; P = .003; 13 studies; 1423 patients; strength of evidence [SOE], moderate), fewer patients with all-cause hospital admissions (39.74% vs 75.00%; RD, -35.26% [95% CI, -49.39% to -21.12%]; OR, 0.22 [95% CI, 0.11-0.43]; P < .001; 1 study; 166 patients; SOE, low), and lower need for intubation (5.34% vs 14.71%; RD, -8.02% [95% CI, -14.77% to -1.28%]; OR, 0.34 [95% CI, 0.14-0.83]; P = .02; 3 studies; 267 patients; SOE, moderate). There was no significant difference in the total number of all-cause hospital admissions (rate ratio, 0.91 [95% CI, 0.71-1.17]; P = .47; 5 studies; 326 patients; SOE, low) or quality of life (standardized mean difference, 0.16 [95% CI, -0.06 to 0.39]; P = .15; 9 studies; 833 patients; SOE, insufficient). Noninvasive HMV use compared with no device was significantly associated with fewer all-cause hospital admissions (rate ratio, 0.50 [95% CI, 0.35-0.71]; P < .001; 1 study; 93 patients; SOE, low), but not mortality (21.84% vs 34.09%; RD, -11.99% [95% CI, -24.77% to 0.79%]; OR, 0.56 [95% CI, 0.29-1.08]; P = .49; 2 studies; 175 patients; SOE, insufficient). There was no statistically significant difference in the total number of adverse events in patients using NIPPV compared with no device (0.18 vs 0.17 per patient; P = .84; 6 studies; 414 patients). Conclusions and Relevance: In this meta-analysis of patients with COPD and hypercapnia, home BPAP, compared with no device, was associated with lower risk of mortality, all-cause hospital admission, and intubation, but no significant difference in quality of life. Noninvasive HMV, compared with no device, was significantly associated with lower risk of hospital admission, but there was no significant difference in mortality risk. However, the evidence was low to moderate in quality, the evidence on quality of life was insufficient, and the analyses for some outcomes were based on small numbers of studies.

A systematic review and meta-analysis of revascularization outcomes of infrainguinal chronic limb-threatening ischemia.

BACKGROUND: The optimal strategy for revascularization in infrainguinal chronic limb-threatening ischemia (CLTI) remains debatable. Comparative trials are scarce, and daily decisions are often made using anecdotal or low-quality evidence. METHODS: We searched multiple databases through May 7, 2017, for prospective studies with at least 1-year follow-up that evaluated patient-relevant outcomes of infrainguinal revascularization procedures in adults with CLTI. Independent pairs of reviewers selected articles and extracted data. Random-effects meta-analysis was used to pool outcomes across studies. RESULTS: We included 44 studies that enrolled 8602 patients. Periprocedural outcomes (mortality, amputation, major adverse cardiac events) were similar across treatment modalities. Overall, patients with infrapopliteal disease had higher patency rates of great saphenous vein graft at 1 and 2 years (primary: 87%, 78%; secondary: 94%, 87%, respectively) compared with all other interventions. Prosthetic bypass outcomes were notably inferior to vein bypass in terms of amputation and patency outcomes, especially for below knee targets at 2 years and beyond. Drug-eluting stents demonstrated improved patency over bare-metal stents in infrapopliteal arteries (primary patency: 73% vs 50% at 1 year), and was at least comparable to balloon angioplasty (66% primary patency). Survival, major amputation, and amputation-free survival at 2 years were broadly similar between endovascular interventions and vein bypass, with prosthetic bypass having higher rates of limb loss. Overall, the included studies were at moderate to high risk of bias and the quality of evidence was low. CONCLUSIONS: There are major limitations in the current state of evidence guiding treatment decisions in CLTI, particularly for severe anatomic patterns of disease treated via endovascular means. Periprocedural (30-day) mortality, amputation, and major adverse cardiac events are broadly similar across modalities. Patency rates are highest for saphenous vein bypass, whereas both patency and limb salvage are markedly inferior for prosthetic grafting to below the knee targets. Among endovascular interventions, percutaneous transluminal angioplasty and drug-eluting stents appear comparable for focal infrapopliteal disease, although no studies included long segment tibial lesions. Heterogeneity in patient risk, severity of limb threat, and anatomy treated renders direct comparison of outcomes from the current literature challenging. Future studies should incorporate both limb severity and anatomic staging to best guide clinical decision making in CLTI.

Can Patients Trust Online Health Information? A Meta-narrative Systematic Review Addressing the Quality of Health Information on the Internet.

BACKGROUND: The Internet has become a leading source of health information accessed by patients and the general public. It is crucial that this information is reliable and accurate. OBJECTIVES: The purpose of this systematic review was to evaluate the overall quality of online health information targeting patients and the general public. METHODS: The systematic review is based on a pre-established protocol and is reported according to the PRISMA statement. Eleven databases and Internet searches were performed for relevant studies. Descriptive statistics were used to synthesize data. The NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies was used to assess the methodological quality of the included studies. RESULTS: Out of 3393 references, we included 153 cross-sectional studies evaluating 11,785 websites using 14 quality assessment tools. The quality level varied across scales. Using DISCERN, none of the websites received a category of excellent in quality, 37-79% were rated as good, and the rest were rated as poor quality. Only 18% of websites were HON Code certified. Quality varied by affiliation (governmental was higher than academic, which was higher than other media sources) and by health specialty (likely higher in internal medicine and anesthesiology). CONCLUSION: This comprehensive systematic review demonstrated suboptimal quality of online health information. Therefore, the Internet at the present time does not provide reliable health information for laypersons. The quality of online health information requires significant improvement which should be a mandate for policymakers and private and public organizations.

Persistent intestinal metaplasia after endoscopic eradication therapy of neoplastic Barrett's esophagus increases the risk of dysplasia recurrence: meta-analysis.

BACKGROUND AND AIMS: Endoscopic eradication therapy (EET) is the main treatment for dysplastic Barrett's esophagus and intramucosal adenocarcinoma. Although the goal of EET is to achieve complete remission of intestinal metaplasia (CRIM), treatment might achieve complete remission of dysplasia (CR-D) only, without achieving CRIM. Persistent intestinal metaplasia after eradication of dysplasia might carry a higher risk for progression into advanced neoplasia. METHODS: We performed a systematic review and meta-analysis after searching multiple databases to identify studies that evaluated dysplasia recurrence risk after successful eradication of neoplasia with EET. We calculated the pooled cumulative incidence of dysplasia and advanced neoplasia recurrence after CRIM and CR-D only and then compared the two using risk ratios. RESULTS: Forty studies were included (4410 patients with total follow-up of 12,976 patient-years). A total of 4061 achieved CRIM and 349 achieved CR-D only. The cumulative incidence of CR-D only was 14% (95% confidence interval [CI], 10%-19%). The pooled cumulative incidence of any dysplasia recurrence after achieving CRIM was 5% (95% CI, 3%-7%) and 12% (95% CI, 4%-23%) after achieving CR-D only. Comparing dysplasia detection after achieving CR-D only with CRIM, there was a significantly higher risk for detection after CR-D (risk ratio [RR], 2.8; 95% CI, 1.7-4.6). The pooled cumulative incidence rate of high-grade dysplasia (HGD)/esophageal adenocarcinoma (EAC) recurrence was 3% (95% CI, 2%-4%) after achieving CRIM and 6% (95% CI, 0%-16%) after achieving CR-D only. Comparing HGD/EAC recurrence after achieving CR-D only with CRIM, there was a significantly higher risk for recurrence after CR-D (RR, 3.6; 95% CI, 1.45-9). When excluding patients who underwent ablation for non-dysplastic Barrett's esophagus only, these differences persisted with dysplasia recurrence after achieving CR-D only compared with CRIM showing a significantly higher risk for recurrence after CR-D (RR, 2.9; 95% CI, 1.66-5). CONCLUSIONS: CRIM was associated with a lower risk of dysplasia and advanced neoplasia recurrence compared with CR-D only. Achieving CRIM should remain the goal of EET in dysplastic Barrett's esophagus.

A systematic review and meta-analysis of revascularization outcomes of infrainguinal chronic limb-threatening ischemia.

BACKGROUND: The optimal strategy for revascularization in infrainguinal chronic limb-threatening ischemia (CLTI) remains debatable. Comparative trials are scarce, and daily decisions are often made using anecdotal or low-quality evidence. METHODS: We searched multiple databases through May 7, 2017, for prospective studies with at least 1-year follow-up that evaluated patient-relevant outcomes of infrainguinal revascularization procedures in adults with CLTI. Independent pairs of reviewers selected articles and extracted data. Random-effects meta-analysis was used to pool outcomes across studies. RESULTS: We included 44 studies that enrolled 8602 patients. Periprocedural outcomes (mortality, amputation, major adverse cardiac events) were similar across treatment modalities. Overall, patients with infrapopliteal disease had higher patency rates of great saphenous vein graft at 1 and 2 years (primary: 87%, 78%; secondary: 94%, 87%, respectively) compared with all other interventions. Prosthetic bypass outcomes were notably inferior to vein bypass in terms of amputation and patency outcomes, especially for below knee targets at 2 years and beyond. Drug-eluting stents demonstrated improved patency over bare-metal stents in infrapopliteal arteries (primary patency: 73% vs 50% at 1 year), and was at least comparable to balloon angioplasty (66% primary patency). Survival, major amputation, and amputation-free survival at 2 years were broadly similar between endovascular interventions and vein bypass, with prosthetic bypass having higher rates of limb loss. Overall, the included studies were at moderate to high risk of bias and the quality of evidence was low. CONCLUSIONS: There are major limitations in the current state of evidence guiding treatment decisions in CLTI, particularly for severe anatomic patterns of disease treated via endovascular means. Periprocedural (30-day) mortality, amputation, and major adverse cardiac events are broadly similar across modalities. Patency rates are highest for saphenous vein bypass, whereas both patency and limb salvage are markedly inferior for prosthetic grafting to below the knee targets. Among endovascular interventions, percutaneous transluminal angioplasty and drug-eluting stents appear comparable for focal infrapopliteal disease, although no studies included long segment tibial lesions. Heterogeneity in patient risk, severity of limb threat, and anatomy treated renders direct comparison of outcomes from the current literature challenging. Future studies should incorporate both limb severity and anatomic staging to best guide clinical decision making in CLTI.