Citations

Introduction The purpose of this systematic review and meta-analysis was to evaluate the diagnostic accuracy of liver and spleen stiffness on magnetic resonance elastography (MRE) for detecting clinically significant portal hypertension. Methods A systematic review of MEDLINE, EMBASE, Scopus, the Cochrane Library, and the Grey Literature through to 15 August 2019 was performed. Original articles with >10 patients evaluating liver and/or spleen stiffness on MRE using a reference standard of portal hypertension defined as intractable ascites, esophageal varices, encephalopathy and/or death were included in analysis. Patient, clinical, MRI, and diagnostic performance was independently acquired by two reviewers. Meta-analysis was performed using a bivariate mixed-effects regression model. Results Fourteen studies were included with 12 studies evaluating liver stiffness and eight studies evaluating spleen stiffness. The pooled and weighted sensitivity, specificity, and area under the curve (AUC) values for liver stiffness on MRE were 83% [95% confidence interval (CI) 72–90%], 80% (95% CI 70–88%), and 88% (95% CI 85–91%), respectively. The pooled and weighted sensitivity, specificity, and AUC values for spleen stiffness on MRE were 79% (95% CI 61–90%), 90% (95% CI 80–95%), and 92% (95% CI 89–94%), respectively. The liver and spleen stiffness sensitivity and specificity values were comparable when evaluating for esophageal varices only at of 80% (95% CI 66–89%) and 76% (95% CI 62–86%) for liver stiffness, and 75% (95% CI 52–90%) and 89% (95% CI 70–96%) for spleen stiffness. Discussion Liver and spleen stiffness on MRE can serve as a supplemental noninvasive assessment tools for detecting clinically significant portal hypertension. Spleen stiffness may be more specific and accurate than liver stiffness for detecting portal hypertension.

AbstractOver the last 5 years, there have been more than 140 new drug approvals in the field of Oncology alone, all based on newly published clinical trials. These approvals have led to an ongoing change in clinical practice, offering new therapeutic options for patients. Therefore, it is important for healthcare providers to be able to appraise a clinical trial and determine its validity, understand its results, and be able to apply such results to their patients. In this guide, we provide a simplified approach tailored to practicing clinicians and trainees. The same concepts and principles apply to other medical specialties.

Objectives The primary objective was to examine the association between hyperlipidaemia (HLP) and 5-year survival after incident acute myocardial infarction (AMI). The secondary objectives were to assess the effect of HLP on survival to discharge across patient subgroups, and the impact of statin prescription, intensity and long-term statin adherence on 5-year survival. Methods Retrospective cohort study of 7071 patients hospitalised for AMI at Mayo Clinic from 2001 through 2011. Of these, 2091 patients with HLP (age (mean±SD) 69.7±13.5) were propensity score matched to 2091 patients without HLP (age 70.6±14.2). Results In matched patients, HLP was associated with higher rate of survival to discharge than no HLP (95% vs 91%; log-rank <0.0001). At year 5, the adjusted HR for all-cause mortality in patients with HLP versus no HLP was 0.66 (95% CI 0.58–0.74), and patients with prescription statin versus no statin was 0.24 (95% CI 0.21 to 0.28). The mean survival was 0.35 year greater in patients with HLP than in those with no HLP (95% CI 0.25 to 0.46). Patients with HLP gained on an average 0.17 life year and those treated with statin 0.67 life year at 5 years after AMI. The benefit of concurrent HLP was consistent across study subgroups. Conclusions In patients with AMI, concomitant HLP was associated with increased survival and a net gain in life years, independent of survival benefit from statin therapy. The results also reaffirm the role of statin prescription, intensity and adherence in reducing the mortality after incident AMI.

Abstract Objectives While anti-tumor necrosis factor alpha (anti-TNFa) therapies for Crohn disease (CD) were initially introduced in 1998 for biologic therapies are often introduced after a minimum of 6 years after diagnosis. The benefit of anti-TNFa early in the course of CD is still controversial, with some studies showing better outcomes but others not. To determine whether earlier introduction of anti-TNFa therapy improves efficacy in clinical trials or clinical series, we aimed to perform a meta-analysis comparing early vs late anti-TNFa use in the management of CD. Methods A comprehensive search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus was conducted from each database’s inception to November 3, 2019. We included comparative studies of early vs late use of anti-TNFa therapy in adult patients with CD. Results Eleven studies were included in the analysis, with a total of 2501 patients. Meta-analysis demonstrated that the early use of anti-TNFa was associated with a statistically significant decrease in the need for surgery (relative risk [RR] = 0.43; 95% confidence interval [CI], 0.26–0.69; I2 = 68%) and disease progression (RR = 0.51; 95% CI, 0.35–0.75; I2 = 61%). Early use also showed an increase in early remission (RR = 1.94; 95% CI, 1.54–2.46; I2 = 0%) and clinical response. There was no statistically significant difference in achieving late remission (RR = 1.39; 95% CI, 0.94–2.05; I2 = 65%) or mucosal healing (RR = 1.10; 95% CI, 0.63–1.91; I2 = 0%). Conclusion This systematic review suggests that using anti-TNFa earlier in the treatment of CD (within 3 years) may improve clinical outcomes compared to late administration in terms of achieving early clinical remission, clinical response, disease progression, and the need for surgery.

ABSTRACT Aims Left atrial (LA) mechanical function may play a significant role in the development and progression of heart failure with preserved ejection fraction (HFpEF). We performed a systematic review and meta-analysis to evaluate association of impaired LA function with outcomes in HFpEF. Methods and results Multiple databases were searched for original studies measuring different phases of LA function in HFpEF patients. Comparative LA function between HFpEF patients and healthy controls was assessed by pooling weighted mean differences (WMD). Adjusted hazard ratios (HRs) with 95% confidence intervals were pooled to evaluate the prognostic utility of LA function. Twenty-two studies (2 trials, 20 observational) comprising 1974 HFpEF patients and 751 healthy controls were included. HFpEF patients had decreased LA reservoir [WMD = −12.21% (−15.47, −8.95); P &lt; 0.001], LA conduit [WMD = −5.68% (−8.56, −2.79); P &lt; 0.001], and pump [WMD = −11.07% (−14.81, −7.34); P &lt; 0.001] emptying fractions compared with controls. LA reservoir [WMD = −13.38% (−16.07, −10.68); P &lt; 0.001], conduit [WMD = −4.09% (−6.77, −1.42); P = 0.003], and pump [WMD = −3.53% (−4.47, −2.59); P &lt; 0.001] strains were also significantly lower in HFpEF patients. Decreased LA reservoir strain [HR 1.24 (1.02, 1.50); P = 0.03] was significantly associated with risk of composite all-cause mortality or heart failure hospitalization. Conclusions Impaired LA function appears to have diagnostic and prognostic value in HFpEF, but whether indices of LA function truly refine discrimination for diagnosis or prognosis remains to be fully determined. Larger studies are needed to better evaluate associations between LA function and clinical outcomes and the role of LA function as a target for novel HFpEF therapies.

Abstract 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.

Background Sudden unexpected death in epilepsy ( SUDEP ) is the leading cause of epilepsy‐related death. SUDEP shares many features with sudden cardiac death and sudden unexplained death in the young and may have a similar genetic contribution. We aim to systematically review the literature on the genetics of SUDEP . Methods and Results PubMed, MEDLINE Epub Ahead of Print, Ovid Medline In‐Process & Other Non‐Indexed Citations, MEDLINE , EMBASE , Cochrane Database of Systematic Reviews, and Scopus were searched through April 4, 2017. English language human studies analyzing SUDEP for known sudden death, ion channel and arrhythmia‐related pathogenic variants, novel variant discovery, and copy number variant analyses were included. Aggregate descriptive statistics were generated; data were insufficient for meta‐analysis. A total of 8 studies with 161 unique individuals were included; mean was age 29.0 (± SD 14.2) years; 61% males; ECG data were reported in 7.5% of cases; 50.7% were found prone and 58% of deaths were nocturnal. Cause included all types of epilepsy. Antemortem diagnosis of Dravet syndrome and autism (with duplication of chromosome 15) was associated with 11% and 9% of cases. The most frequently detected known pathogenic variants at postmortem were in Na + and K + ion channel subunits, as were novel potentially pathogenic variants (11%). Overall, the majority of variants were of unknown significance. Analysis of copy number variant was insignificant. Conclusions SUDEP case adjudication and evaluation remains limited largely because of crucial missing data such as ECG s. The most frequent pathogenic/likely pathogenic variants identified by molecular autopsy are in ion channel or arrhythmia‐related genes, with an ≈11% discovery rate. Comprehensive postmortem examination should include examination of the heart and brain by specialized pathologists and blood storage.