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.     

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。     

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.     

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.     

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     

Effects of physical activity in telomere length: Systematic review and meta-analysis

The aim of this systematic review is to assess the effects of exercise on telomeres length. We searched the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), Scopus, LILACS, SPORTDiscus and Web of Science from inception to August 2014. All articles that assessed the effects of exercise in telomere length were included in this review. The search strategy used the following combinations of terms: telomere AND “motor activity” OR exercise OR “physical activity”. Two reviewers, working independently, screened all titles and abstracts to identify studies that could meet inclusion criteria. Whenever possible, and if appropriate, we performed a random-effect meta-analysis of study outcomes. Thirty-seven original studies were included in this systematic review, including 41,230 participants. Twenty articles did not find statistically significant association, whereas 15 described a positive association. Two papers found an inverted “U” correlation. There is a tendency toward demonstrating an effect of exercise on telomere length. Few prospective studies were found, many studies did not reach statistical significance and there was an important methodological diversity. For this reason, a possible significant association between physical activity and telomere length remains an open question.     

肺腺泡内动脉构形重建与肺动脉高压等的关系

以野百合碱一次性皮下注射复制大鼠肺动脉高压和肺心病模型。应用光镜、电镜、免疫组织化学和形态定量等方法，观察了肺腺泡内动脉不同病变在肺动脉高压中的作用。结果表明了肺循环功能与结构之间的关系，反映出肺腺泡内动脉构形重建是肺动脉高压形成的病理学基础。结果提示肺腺泡内动脉壁周细胞的增生和肌样分化，对无肌型肺动脉的肌化意义重大。     

Polymorphism of the fractalkine receptor CX3CR1 and systemic sclerosis-associated pulmonary arterial hypertension

Fractalkine (FKN) and its receptor CX3CR1 are critical mediators in the vascular and tissue damage of several chronic diseases, including systemic sclerosis (SSc) and pulmonary arterial hypertension (PAH). Interestingly, the V249I and T280M genetic polymorphisms influence CX3CR1 expression and function. We investigated whether these polymorphisms are associated with PAH secondary to SSc. CX3CR1 genotypes were analyzed by PCR and sequencing in 76 patients with limited SSc and 204 healthy controls. PAH was defined by colorDoppler echocardiography. Homozygosity for 249II as well as the combined presence of 249II and 280MM were significantly more frequent in patients with SSc compared to controls (17 vs 6%, p = 0.0034 and 5 vs 1%, p = 0.0027, respectively). The 249I and 280M alleles were associated with PAH (odd ratio [OR] 2.2, 95% confidence interval [CI] 1.01-4.75, p = 0.028 and OR 7.37, 95%CI: 2.45-24.60, p = 0.0001, respectively). In conclusion, the increased frequencies of 249I and 280M CX3CR1 alleles in a subgroup of patients with SSc-associated PAH suggest a role for the fractalkine system in the pathogenesis of this condition. Further, the 249I allele might be associated with susceptibility to SSc.