Factors associated with pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc)

BackgroundPulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) is a lethal complication affecting 8–15% of patients. Screening tests such as echocardiography and pulmonary function tests allow for triaging patients for diagnosis by right heart catheterization. Understanding risk factors of SSc-PAH could help differentiate high-risk patients.MethodsA systematic review was conducted to determine associations with SSc-PAH, including clinical/disease characteristics, antibodies, labs and biomarkers. The frequencies of publications featuring each risk/association were reported.ResultsAmong 2654 articles, 984 duplicates and 1578 irrelevant articles were removed, leaving 92 articles for manual screening. After excluding 55 papers with small sample sizes, publications from identical cohorts, not English language, or PAH not ascertained by RHC, 37 articles were eligible. A total of 43 factors for SSc-PAH were identified within seven categories. Several associations were due to PAH and risk factors such as dynpnea, right heart failure, and short 6-minute walk distance. Patient characteristics (14), pulmonary physiology (6), antibody profiles (6) and genetics/epigenetics (6) had the most numerous and diverse factors, while biomarkers (4) and other labs (2) features were infrequent. Low carbon monoxide (DLCO) (6), older age (4), longer disease duration (4), positive anticentromere antibodies (ACA) (4), telangiectasias (4), high brain natriuretic peptide (4) were frequent associations.ConclusionsRisk factors for SSc-PAH such as ACA, older age, longer disease duration limited cutaneous SSc subset and presence of ILD may enrich screening programs. Genes and other antibody profiles are inconsistent and requires further validation.     

The association of IL-33 and systemic sclerosis: a systematic review and meta-analysis

Immunologic Research - A meta-analysis of the association between IL-33 and these diseases is lacking, and we aimed to perform a meta-analysis of the association between IL-33 and systemic...     

Worldwide prevalence of Lynch syndrome in patients with colorectal cancer: Systematic review and meta-analysis

PurposeLynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome, with an estimated prevalence of 2% to 3% of CRC. A prevalence study is needed to provide accurate estimates of the true prevalence of LS.MethodsMEDLINE (Ovid), Embase, and Web of Science were searched. Prevalence was calculated by random effects meta-analysis models. I² score was used to assess heterogeneity across studies. Meta-regression was performed for between-study variance.ResultsA total of 51 studies were included in this review. The overall pooled yield of LS screening was 2.2% based on all methods of detection. Studies performing germline tests on all participants with CRC reported higher prevalence (5.1%) as opposed to studies only performing germline tests on participants with tumors with mismatch repair deficiency (1.6%) or microsatellite instability (1.1%). Selected cohorts of CRC had a higher prevalence of germline LS diagnoses.ConclusionLS prevalence across multiple ethnic, geographic, and clinical populations is remarkably similar. Universal germline testing of patients presenting with cancer identifies that most CRCs are attributed to LS. Young patients presenting with CRC and those who fulfill criteria for a familial risk provide the highest returns for LS identification. Our study supports the universal germline CRC screening for LS.     

Global prevalence of depression and anxiety in patients with hepatocellular carcinoma: Systematic review and meta-analysis

Background/AimsDepression and anxiety are associated with poorer outcomes in patients with hepatocellular carcinoma (HCC). However, the prevalence of depression and anxiety in HCC are unclear. We aimed to establish the prevalence of depression and anxiety in patients with HCC.MethodsMEDLINE and Embase were searched and original articles reporting prevalence of anxiety or depression in patients with HCC were included. A generalized linear mixed model with Clopper-Pearson intervals was used to obtain the pooled prevalence of depression and anxiety in patients with HCC. Risk factors were analyzed via a fractional-logistic regression model.ResultsSeventeen articles involving 64,247 patients with HCC were included. The pooled prevalence of depression and anxiety in patients with HCC was 24.04% (95% confidence interval [CI], 13.99–38.11%) and 22.20% (95% CI, 10.07–42.09%) respectively. Subgroup analysis determined that the prevalence of depression was lowest in studies where depression was diagnosed via clinician-administered scales (16.07%;95% CI, 4.42–44.20%) and highest in self-reported scales (30.03%; 95% CI, 17.19–47.01%). Depression in patients with HCC was lowest in the Americas (16.44%; 95% CI, 6.37–36.27%) and highest in South-East Asia (66.67%; 95% CI, 56.68–75.35%). Alcohol consumption, cirrhosis, and college education significantly increased risk of depression in patients with HCC.ConclusionsOne in four patients with HCC have depression, while one in five have anxiety. Further studies are required to validate these findings, as seen from the wide CIs in certain subgroup analyses. Screening strategies for depression and anxiety should also be developed for patients with HCC.     

Causes and prevalence of inadequate pulmonary function testing among patients with systemic sclerosis

Introduction

Spirometry is a screening tool for evaluating the degree of restrictive lung disease in systemic sclerosis (SSc). Observations indicated that some patients could not complete the test. The aim of the study was to identify the prevalence, causes and clinical predictors of an inadequate pulmonary function test (PFT) in SSc.

Material and methods

A cross-sectional study was performed among SSc patients over 18 years old followed up at Srinagarind Hospital, Khon Kaen, Thailand, during January 2006–December 2012. The adequacy of the PFT was based on the acceptable blow criteria as set out by the American Thoracic Society and the European Respiratory Society 2005 Standardizations of Spirometry.

Results

Two hundred and forty-nine patients were included (female to male ratio was 2 : 1). The mean age at performing PFT was 51.4 ±11.1 years (range: 19.6–79.5). Median duration of disease at performing PFT was 2 years (IQR: 0.6–4.4). Inadequate PFT occurred in 73 cases (prevalence 29.3%: 95% CI: 23.6–35.0); the majority (60 cases; 82.2%) had an expiration time < 6 s and the others were due to plateau < 1 s (11 cases; 15%), air leak around mouth piece (1 case; 1.4%) and hesitation (1 case; 1.4%). Thirteen of 73 (17.8%) had an unusable graph with the overall prevalence of 5.2% (95% CI: 2.4–8.0). The factor associated with inadequate PFT was docy mass index (BMI) < 18.5 kg/m² (OR = 2.17: 95% CI: 1.49–3.17); the same factor was associated with an unusable graph, which was confirmed by the multivariate analysis (OR = 5.21; 95% CI: 1.60–16.95).

Conclusions

One-third of Thai SSc patients had an inadequate pulmonary function test – the majority because of inadequate time for expiring. Low BMI influenced the effectiveness of the test, leading to an incomplete graph for evaluating lung disease in SSc.     

利妥昔单抗治疗系统性红斑狼疮相关肺动脉高压的前景

肺动脉高压(PAH)是系统性红斑狼疮(SLE)的一种严重并发症,近期研究发现T、B淋巴细胞在PAH的发生过程中发挥重要作用。以B细胞为靶向,而同样对T细胞造成影响的利妥昔单抗(RTX)可能成为治疗SLE相关PAH(SLE-PAH)的有力武器。     

Leukotrienes in pulmonary arterial hypertension

Leukotrienes (LTs) are lipid mediators derived from the 5-lipoxygenase (5-LO) pathway of arachidonic acid metabolism and are markers and mediators of pulmonary inflammation. Research over the past two decades has established that LTs modulate inflammation in pulmonary arterial hypertension (PAH). The purpose of this review was to summarize the current knowledge of LTs in the pathophysiology of PAH and to highlight a recent study that advances our understanding of how leukotriene B₄ (LTB₄) specifically contributes to pulmonary vascular remodeling. The results of these studies suggest that pharmacological inhibition of LT pathways, especially LTB₄, has high potential for the treatment of PAH.     

Human mesenchymal stem cells for the management of systemic sclerosis. Systematic review

IntroductionSistemic Sclerosis (SSc) is a heterogeneous autoimmune disease with a high rate of progression and therapeutic failure, and treatment is a challenge, new therapeutic proposals being needed, being mesenchymal stem cells (MSCs) considered as alternative therapy for SSc for its immunomodulatory capacity. We evaluated the efficacy and safety of human MSC (hMSC) in patients with SSc through a systematic literature review (SLR).MethodsSLR (PRISMA guideline) on MEDLINE/OVID, LILACS, EMBASE, and Cochrane/OVID bases (until July 2020, without limits). All types of clinical studies were considered: patients ≥18 years old with SSc and treatment with hMSC. Exclusion criteria: animal models, autologous/allogenic hematopoietic stem cell transplants, narrative reviews, letters to the editor. MeSH and “Key word” terms were used. The level of evidence and the quality rating were rated [Joanna Briggs Institute (JBI) lists]. Registration in PROSPERO repository (ID CRD42020185245) The Synthesis Without Meta-analysis (SWiM) guideline was followed.ResultsWe initially identified 508 articles, of which 11 were finally included (8 case series and 3 case reports). The 11 articles included 101 patients (85 female, age range 18–75 years). The level of evidence was mostly 4 (JBI); the quality of evidence was met (≥50% of JBI items). SWiM showed that vascular skin involvement (digital ulcers, necrosis, and gangrene) and associated pain were the predominant outcomes, while improvements were found in almost all cases. One patient died in the first month, and the frequency of complications was low. Expanded hMSCs were used in 24 patients and other cell sources in the remaining patients.ConclusionThere is too little reported data to reach definite conclusions about the use of hMSC in SSc. Further studies with better epidemiological designs are needed to evaluate the benefit of hMSCs in SSc patients.     

Prevalence of multidrug-resistant tuberculosis in prisons: Systematic review and meta-analysis

BackgroundIn the context of prisons, multidrug-resistant tuberculosis (MDR-TB) is a major problem. In this article, we estimate the prevalence of MDR-TB among the population deprived of freedom from countries in South America, Europe, Asia and Africa.MethodsThe articles were retrieved through systematic search at four databases (EMBASE, CINAHL, LILACS and MEDILINE). The meta-analysis was developed by the random effect model, using the Mantel-Haenszel method, with presentation of the aggregated results through the forest plot. The degree of heterogeneity between the studies was verified using Cochran's Q test and I².ResultsOf the 102 articles analyzed, 21 were included in this systematic review. The analysis showed heterogeneity indicated by the Q test (P ?< ?0.001) and I² statistics (I² ?= ?50.52%). The funnel graph and Egger test (P ?< ?0.830) showed symmetry between investigations. The grouped prevalence of MDR-TB was 0.48% (95% CI: 0.02 to 1.32), advancing to 1.15 (95% CI: 0.15 to 2.73) when culture and sensitivity test were considered by the authors. No specific characteristics were significantly associated with differences in prevalence rates in the population deprived of freedom.ConclusionThe study reaffirms the magnitude of MDR-TB in the population deprived of freedom in the world context. Political and technical-scientific efforts should be mobilized to mitigate TB and MDR-TB in prisons and for successful national and international disease control programs.     

Sildenafil in pediatric pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a life-threatening disease of varied etiologies. Although PAH has no curative treatment, a greater understanding of pathophysiology, technological advances resulting in early diagnosis, and the availability of several newer drugs have improved the outlook for patients with PAH. Sildenafil is one of the therapeutic agents used extensively in the treatment of PAH in children, as an off-label drug. In 2012, the United States Food and Drug Administration (USFDA) issued a warning regarding the of use high-dose sildenafil in children with PAH. This has led to a peculiar situation where there is a paucity of approved therapies for the management of PAH in children and the use of the most extensively used drug being discouraged by the regulator. This article provides a review of the use of sildenafil in the treatment of PAH in children.KEY WORDS: Child, phosphodiesterase (PDE)-5 inhibitor, Pulmonary hypertension therapy