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Abstract Context Hyperthyroidism is associated with low levels of cholesterol and triglycerides, and hypothyroidism is associated with hypercholesterolemia and hypertriglyceridemia. Objective The aim of this systematic review was to investigate the impact of therapy for overt and subclinical hyper- and hypothyroidism on serum lipids. Data Sources We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus from 1970 through April 5, 2018. Study Selection Pairs of independent reviewers selected randomized and observational studies evaluating lipid parameters in patients undergoing treatment for hyper- or hypothyroidism. Data Extraction Pairs of independent reviewers extracted data and appraised studies. Data Synthesis Treatment of overt hyperthyroidism showed a significant increase in total cholesterol (TC) by 44.50 mg/dL (95% confidence interval [CI]: 37.99, 51.02), low-density lipoprotein cholesterol (LDL-C) by 31.13 mg/dL (95% CI: 24.33, 37.93), high-density lipoprotein cholesterol (HDL-C) by 5.52 mg/dL (95% CI: 1.48, 9.56), apolipoprotein A (Apo A) by 15.6 mg/dL (95% CI: 10.38, 20.81), apolipoprotein B (apo B) by 26.12 mg/dL (95% CI: 22.67, 29.57), and lipoprotein (Lp[a]) by 4.18 mg/dL (95% CI: 1.65, 6.71). There was no significant change in triglyceride (TG) levels. Treatment of subclinical hyperthyroidism did not change any lipid parameters significantly. Levothyroxine therapy in overt hypothyroidism showed a statistically significant decrease in TC by -58.4 mg/dL (95% CI: -64.70, -52.09), LDL-C by -41.11 mg/dL (95% CI: -46.53, -35.69), HDL-C by -4.14 mg/dL (95% CI: -5.67, -2.61), TGs by -7.25 mg/dL (95% CI: -36.63, 17.87), apo A by -12.59 mg/dL (95% CI: -17.98, -7.19), apo B by -33.96 mg/dL (95% CI: 41.14, -26.77), and Lp(a) by -5.6 mg/dL (95% CI: -9.06, -2.14). Levothyroxine therapy in subclinical hypothyroidism showed similar changes but with a smaller magnitude. The studies contained varied population characteristics, severity of thyroid dysfunction, and follow-up duration. Conclusions Treatment of overt but not subclinical hyperthyroidism is associated with worsening of the lipid profile. Levothyroxine therapy in both overt and subclinical hypothyroidism leads to improvement in the lipid profile, with a smaller magnitude of improvement in subclinical hypothyroidism.

INTRODUCTION: To assess the effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on acid reflux and esophageal motor function and to evaluate the observation of esophageal adenocarcinoma (EAC) after bariatric surgery. METHODS: We searched 5 databases for adults who underwent SG or RYGB and had esophageal pH test and/or esophageal manometry before and after surgery. A separate systemic search of observational studies and a retrospective review at 3 institutions of adults who developed EAC after these surgeries were conducted. Outcomes were changes in manometric and pH parameters and EAC cases after SG and RYGB. RESULTS: A total of 27 nonrandomized studies (SG: 612 patients; RYGB: 470 patients) were included. After SG, lower esophageal sphincter pressure and esophageal body amplitude were decreased and the risk of ineffective esophageal motility was increased. Total and recumbent acid exposure times were increased. After RYGB, an increased risk of ineffective esophageal motility was observed. Total, upright, and recumbent acid exposure times were decreased. The total reflux episodes remained unchanged but with increased nonacid reflux and decreased acid reflux events. Including our largest series, 31 EAC cases have been reported to date after SG and RYGB. DISCUSSION: This systematic review demonstrates increased acid reflux after SG and decreased acid reflux after RYGB. An observed increased nonacid reflux after RYGB might contribute to failure of gastroesophageal reflux disease improvement. This refluxate might be noxious to the esophagus, warranting further studies. RYGB might not entirely preserve esophageal function as previously believed.

ObjectiveAntirheumatic disease therapies have been used to treat coronavirus disease 2019 (COVID‐19) and its complications. We conducted a systematic review and meta‐analysis to describe the current evidence.MethodsA search of published and preprint databases in all languages was performed. Included studies described ≥1 relevant clinical outcome for ≥5 patients who were infected with severe acute respiratory syndrome coronavirus 2 and were treated with antirheumatic disease therapy between January 1, 2019 and May 29, 2020. Pairs of reviewers screened articles, extracted data, and assessed risk of bias. A meta‐analysis of effect sizes using random‐effects models was performed when possible.ResultsThe search identified 3,935 articles, of which 45 were included (4 randomized controlled trials, 29 cohort studies, and 12 case series). All studies evaluated hospitalized patients, and 29 of the 45 studies had been published in a peer‐reviewed journal. In a meta‐analysis of 3 cohort studies with a low risk of bias, hydroxychloroquine use was not significantly associated with mortality (pooled hazard ratio [HR] 1.41 [95% confidence interval (95% CI) 0.83, 2.42]). In a meta‐analysis of 2 cohort studies with some concerns/higher risk of bias, anakinra use was associated with lower mortality (pooled HR 0.25 [95% CI 0.12, 0.52]). Evidence was inconclusive with regard to other antirheumatic disease therapies, and the majority of other studies had a high risk of bias.ConclusionIn this systematic review and meta‐analysis, hydroxychloroquine use was not associated with benefit or harm regarding COVID‐19 mortality. The evidence supporting the effect of other antirheumatic disease therapies in COVID‐19 is currently inconclusive.

AbstractSevere cases of COVID-19 infection, often leading to death, have been associated with variants of acute respiratory distress syndrome (ARDS). Cell therapy with mesenchymal stromal cells (MSCs) is a potential treatment for COVID-19 ARDS based on preclinical and clinical studies supporting the concept that MSCs modulate the inflammatory and remodeling processes and restore alveolo-capillary barriers. The authors performed a systematic literature review and random-effects meta-analysis to determine the potential value of MSC therapy for treating COVID-19-infected patients with ARDS. Publications in all languages from 1990 to March 31, 2020 were reviewed, yielding 2691 studies, of which nine were included. MSCs were intravenously or intratracheally administered in 117 participants, who were followed for 14 days to 5 years. All MSCs were allogeneic from bone marrow, umbilical cord, menstrual blood, adipose tissue, or unreported sources. Combined mortality showed a favorable trend but did not reach statistical significance. No related serious adverse events were reported and mild adverse events resolved spontaneously. A trend was found of improved radiographic findings, pulmonary function (lung compliance, tidal volumes, PaO2/FiO2 ratio, alveolo-capillary injury), and inflammatory biomarker levels. No comparisons were made between MSCs of different sources.Significance statement The potential benefits of mesenchymal stromal cell (MSC) therapy for patients with COVID-19 acute respiratory distress syndrome support the rapid commencement of clinical trials, as well as the compassionate use of MSCs that already have documented safety profiles from FDA-approved studies.

e19530 Background: Intensive chemotherapy (IC) regimens are rarely used in patients with myelodysplastic syndromes (MDS) for many reasons including advanced age at diagnosis, the frailty of these patients, the presence of several comorbidities and potentially increased mortality when such regimens are used. Additionally, very little literature exists on its safety and long-term benefit in this population. Aim: To evaluate the safety and effectiveness of IC regimens in patients with MDS. Methods: We searched MEDLINE, Embase, Scopus and Cochrane databases from each database's inception from 1990 to January 27th, 2020. Keywords include: “MDS”, “induction chemotherapy” and “remission induction”. Studies evaluating different IC regimens with MDS were included. IC studies for patients with relapsed/ refractory MDS were excluded. Studies that combined acute myeloid leukemia (AML) and MDS outcomes were excluded. The random-effects model was used to pool relative risks and incidence rates. Main endpoints were overall remission rates (ORR), 30- and 60-days mortality, 1-year, 2-year and 5-year overall survival (OS). Results: Characteristics: From 2001 records, we included 13 studies [1,164 patients, median age 60.1 years (range, 17-88), males 58.9%, 58.4% patients had abnormal cytogenetics, median bone marrow blasts 17.8% (range 4 -29%), 4 studies were randomized]. Induction outcome: IC regimes included “7+3, FLAG, s-HAM, and few other regimens. Response: ORR was 55%, including 52% CR rate. Safety: 30- and 60-days mortality were 7%, 15%, respectively. Survival outcome: median survival was 11.6 months, 1-year, 2-year and 5-year OS were 48%, 21% and 5%, respectively. Randomized studies comparison: adding growth factors to IC did not show statistically significant effects on outcomes regarding induction mortality, ORR and OS (p-value > .05). Conclusions: IC is rarely used in MDS patients and its use is associated with high mortality rates and low long-term survival. Limitations to our studies include the long span of this review over 3 decades and the difficulty of using published studies that combines MDS and AML patients’ outcome. More studies are needed in this population of interest in the future.

INTRODUCTION: We applied the Grading of Recommendations, Assessment, Development, and Evaluation framework to evaluate the performance of fecal calprotectin (FC) as an alternative to endoscopy in patients with moderate-to-severe ulcerative colitis (UC) treated with a biologic agent or tofacitinib. METHODS: Individual participant data from the trials of infliximab, golimumab, vedolizumab, and tofacitinib for UC were pooled to generate prevalence of endoscopic activity (Mayo endoscopy score) across different combinations of the rectal bleeding score (RBS) and stool frequency score (SFS). These estimates were then combined with the data from an updated systematic review of the operating properties of FC to generate clinical scenario–specific assessments of the performance of FC as a predictor of endoscopic disease activity. A prespecified threshold of acceptability for false-negative (FN) and false-positive (FP) test results was set at 5%. RESULTS: For patients with UC achieving RBS 0 + SFS 0/1, FC ≤ 50 μg/g may avoid endoscopy in 50% patients with a FN rate <5%. Similarly, for patients with RBS 2/3 + SFS 2/3, FC ≥ 250 μg/g potentially avoids endoscopy in approximately 50% patients with an FP rate <5%. The greatest uncertainty in the diagnostic performance for FC was observed in patients with UC achieving RBS 0 but having SFS 2/3, where FN and FP rates were consistently >10%, and endoscopic evaluation may be warranted. DISCUSSION: Two clinical scenarios were identified where FC can be used with confidence for monitoring treatment response to biologics or tofacitinib in patients with UC without the requirement for endoscopy.

Background and Aims Chronic hepatitis B (CHB) can lead to hepatocellular carcinoma (HCC). While both tenofovir disoproxil (TDF) and entecavir (ETV) have been shown to reduce the risk of HCC, their comparative effectiveness is unclear. We estimated the comparative effectiveness of these two agents in reducing the risk of HCC in patients with CHB, through a systematic review and meta‐analysis. Approach and Results We searched multiple electronic databases from January 1, 1998, to October 31, 2019, for randomized controlled trials and observational comparative effectiveness studies in adults with CHB treated with ETV compared to TDF, reporting the incidence of HCC (minimum follow‐up 12 months). Primary outcome was incidence of HCC, calculated as incidence rate ratio (IRR) with 95% confidence interval (CI, unadjusted analysis) and hazard ratio (HR) with 95% CI (adjusted analysis, where reported). Of 1,971 records identified, 14 studies (263,947 person‐years) were included for quantitative analysis. On unadjusted meta‐analysis of 14 studies, the risk of HCC was not statistically different between ETV and TDF (IRR, 1.28; 95% CI, 0.99‐1.66). When using available adjusted data (multivariate or propensity‐matched data), the risk of HCC among patients treated with ETV was 27% higher when compared to TDF (seven studies; 95% CI, 1.01‐1.60, P = 0.04). Additional analysis of adjusted data when separately reported among patients with cirrhosis demonstrated an adjusted HR of 0.90 (95% CI, 0.66‐1.23), suggesting no difference between ETV‐treated and TDF‐treated groups. The overall confidence in estimates was very low (observational studies, high heterogeneity). Conclusions TDF may be associated with lower risk of HCC when compared to ETV.

Background: The prevalence of familial hypercholesterolemia is 1 in 250, but <10% of patients are diagnosed. Cascade testing enables early detection of cases through systematic family tracing. Establishment of familial hypercholesterolemia cascade testing programs in the US could be informed by approaches used elsewhere. Methods: We conducted a systematic review of published studies in the English language of cascade testing for familial hypercholesterolemia, which reported the number of index cases and number of relatives tested and specified methods of contacting relatives and testing modalities methods utilized. For each study, we calculated yield (proportion of relatives who test positive) and new cases per index case, to facilitate comparison. Results: We identified 10 studies from the literature that met inclusion criteria; the mean number of probands and relatives per study was 242 and 826, respectively. The average yield was 44.76% with a range of 30% to 60.5%, and the mean new cases per index case was 1.65 with a range of 0.22 to 8.0. New cases per index case tended to be greater in studies that used direct contact versus indirect contact (2.06 versus 0.86), tested beyond first-degree relatives versus only first-degree relatives (3.65 versus 0.80), used active sample collection versus collection at clinic (4.11 versus 1.06), and utilized genetic testing versus biochemical testing (2.47 versus 0.42). Conclusions: New case detection in familial hypercholesterolemia cascade testing programs tended to be higher with direct contact of relatives, testing beyond first-degree relatives, in-home–based sample collection, and genetic testing. These findings should be helpful for establishing cascade testing programs in the United States.