Baricitinib,a Janus kinase inhibitor,in the treatment of rheumatoid arthritis: a systematic literature review and meta-analysis of randomized controlled trials

Janus kinases (JAKs) play an important role in intracellular signaling for multiple cytokines in the pathogenesis of RA. Baricitinib is an oral, selective JAK 1 and 2 inhibitor which has been shown to be effective in the treatment of RA in several clinical trials. This meta-analysis aims to aggregate currently available data to assess the overall efficacy and safety of baricitinib in RA. We searched PubMed, EMBASE, and Cochrane CENTRAL from inception through 09/24/17 with restriction to English language. We excluded meeting abstracts without full text publication. We used RevMan 5.3 to perform meta-analysis between groups on baricitinib (2 and 4 mg daily) and placebo using random effect model calculating odds ratio (OR) as well as 95% confidence interval (CI). Compared to placebo, 2 mg of baricitinib was more effective in achieving ACR20 [54 vs. 36.6%; OR 2.09; 95% CI 1.60–2.71; p?<?0.00001; I² 0%], ACR50 [31.6 vs. 10.3%; OR 2.3; 95% CI 1.68–3.15; p?<?0.00001; I² 0%], and ACR70 responses [18.7 vs. 5.1%; OR 4.05; 95% CI 2.54–6.44; p?<?0.00001; I² 0%]. Similarly, 4 mg of baricitinib daily was more effective than placebo. Baricitinib 2 mg once daily did not increase any adverse events [65.3 vs. 62.4%; OR 1.03; 95% CI 0.80–1.34; p?=?0.8; I² 0%], serious adverse events [3.5 vs. 5%; OR 0.68; 95% CI 0.37–1.27; p?=?0.22; I² 0%], and herpes zoster [1.2 vs. 0.4%; OR 2.34; 95% CI 0.27–20.47; p?=?0.44; I² 37%] as compared to placebo. Similarly, 4 mg of baricitinib did not increase the risk of serious adverse events but increased herpes zoster infection [OR 3.88; 95% CI 1.36–11.06; p?=?0.01; I² 0%] when compared to placebo. Baricitinib is effective in treatment of RA, and did not appear to have significant safety concerns during the first 6 months of treatment.     

Anti-IL-17 therapy in treatment of rheumatoid arthritis: a systematic literature review and meta-analysis of randomized controlled trials

IL-17 has a role in inflammation in RA, and its levels in joints correlate with disease severity. Multiple RCTs have been performed to study effects of anti-IL-17 agents. The objective of this study was to perform a systematic review and meta-analysis to analyze the efficacy and safety of anti-IL-17 agents in the management of RA. This work is based on a systematic review of studies retrieved by a sensitive search strategy in PubMed, EMBASE and Cochrane CENTRAL from inception through 9/7/15. Study selection criteria were the following: adult patients (age ≥ 18 years) with RAs, random selection of patients for anti-IL-17 therapy and treatment response compared to placebo. We performed systematic literature review per PRISMA guideline and two investigators independently selected seven randomized clinical trials (RCTs) for meta-analysis. We used random effect model calculating odds ratio (OR) and 95 % confidence interval (CI) to measure the efficacy with ACR20/50/70 responses and the safety with adverse events. Seven studies with total of 1226 patients including 905 in anti-IL-17 group and 321 in placebo were included in the meta-analysis. Anti-IL-17 was effective in achieving ACR20 and ACR50 compared to placebo (OR 2.47, 95 % CI 1.29–4.72, P = 0.006, I ² 77 % and OR 2.94, 95 % CI 1.37–6.28, P = 0.005, I ² 64 %, respectively). Data analysis for ACR70 showed a favorable trend toward anti-IL-17 (OR 2.62, 95 % CI 1–6.89, P = 0.05, I ² 15 %). Subgroup analysis of ACR20 for individual anti-IL-17 agents showed that ixekizumab was more effective than placebo, while secukinumab showed a trend toward achieving the ACR20 response. However, brodalumab was not effective compared to placebo. Safety analysis did not show increased risk of any or serious adverse effects by anti-IL-17 compared to placebo (OR 1.23, 95 % CI 0.94–1.61, P = 0.13, I ² = 0 % and OR 1.28, 95 % CI 0.57–2.88, P = 0.55, I ² = 0 %, respectively). This meta-analysis concludes that anti-IL-17 is effective in the treatment of RA without increased risk of any or serious adverse effects; however, the results are limited by significant heterogeneity and small duration of studies.     

CTLA-4 +49A/G gene polymorphism and type 1 diabetes mellitus in the Chinese population: a meta-analysis of 2238 subjects

Previous studies reported that cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) +49A/G gene polymorphism is correlated with type 1 diabetes mellitus (T1DM) risk. However, their results remain disputable. This study aims to discuss the relationship between CTLA-4 +49A/G gene polymorphism and T1DM in a Chinese population. The current meta-analysis involved 2238 participants from seven individual studies. The pooled odds ratio (OR) and its corresponding 95 % confidence interval (95 % CI) were assessed by the random- or fixed-effects model. A significant relationship between CTLA-4 +49A/G gene polymorphism and T1DM was detected under allelic (OR: 1.84, 95 % CI: 1.62–2.10, P?<?0.00001), dominant (OR: 1.152, 95 % CI: 1.062–1.249, P?=?0.001), recessive (OR: 1.631, 95 % CI: 1.443–1.844, P?<?0.00001), and additive (OR: 1.292, 95 % CI: 1.224–1.363, P?<?0.00001) genetic models. A significant relationship exists between CTLA-4 +49A/G gene polymorphism and increased T1DM risk in the Chinese population. Individuals having the G allele of CTLA-4 +49A/G gene polymorphism have a higher risk for T1DM in the Chinese population.     

Prophylactic mesh to prevent parastomal hernia: a meta-analysis of randomized controlled studies

The aim of the present meta-analysis was to determine whether prophylactic mesh decreases the odds of parastomal hernia formation. Randomized controlled trials referenced in MEDLINE or EMBASE between 1946 and 2016 comparing prophylactic mesh to standard stoma formation were included. The primary outcome was occurrence of parastomal hernia. Secondary outcomes were parastomal hernia requiring surgical intervention and complications. Odds ratios were calculated for the primary and secondary outcomes. Subgroup analyses were conducted based on mesh type, mesh location, laparoscopic versus open, and method of hernia diagnosis. Nine randomized controlled trials with 569 participants were included. There was a significant decrease in the odds of developing a parastomal hernia in the prophylactic mesh group [odds ratio (OR) 0.21, 95% confidence interval (CI) 0.11–0.38, p < 0.00001, I ² = 36%], as well as decreased odds of requiring surgical repair (OR 0.36, 95% CI 0.15–0.87, p = 0.02, I ² = 0%). There was no evidence that prophylactic mesh increased the odds of surgical complications (seven studies, OR 1.34, 95% CI 0.73–2.46, p = 0.34, I ² = 34%) or stoma-specific complications (eight studies, OR 0.65, 95% CI 0.40–1.05, p = 0.08, I ² = 0%). There was a subgroup effect with synthetic mesh associated with a lower incidence of parastomal hernias which was not appreciated in the biologic mesh group (test of subgroup effect p = 0.01). Five studies had a high risk of bias. The Grades of Recommendation, Assessment, Development and Evaluation quality of evidence was moderate. Prophylactic mesh is associated with decreased odds of parastomal hernia formation and the need for surgical repair. There is no evidence that mesh placement increases the odds of complications.     

Antiviral therapy with nucleotide/nucleoside analogues in chronic hepatitis B: A meta-analysis of prospective randomized trials

Nucleotide/nucleoside analogues (antiviral therapy) are used in the therapy of HBeAg positive and HBeAg negative chronic hepatitis B. We analyzed ten selected randomized controlled with 2557 patients to estimate the effect of antiviral drugs in chronic hepatitis B with compared to placebo. Virological response, biochemical response, histological response, seroconversion of HBeAg, and loss of HBeAg were estimated as primary efficacy measures. The included studies were subjected for heterogeneity and publication bias. The heterogeneity was assessed with χ2 and I² statistics. Publication bias was assessed by funnel plot. Greater rates of improvement obtained in antiviral group for virological response [43.96 % vs. 3.15 %, RR?=?0.57, 95 % CI?=?0.54–0.61, p-value <0.00001], biochemical response [58.37 % vs. 21.87 %, RR?=?0.52, 95 % CI?=?0.48–0.56, p-value <0.00001], histological response [58.99 % vs. 27.13 %, RR?=?0.56, 95 % CI?=?0.50–0.63, p-value <0.0001], seroconversion of HBeAg [10.66 % vs. 5.56 %, RR?=?0.94, 95 % CI?=?0.91–0.97, p-value?=?0.0005], and HBeAg loss [14.59 % vs. 9.64 %, RR?=?0.92, 95 % CI?=?0.88–0.96, p-value?=?0.0002]. The safety analysis were carried out for adverse events such as headache [17.22 % vs. 17.34 %, OR?=?1.09, 95 % CI?=?0.81–1.46, p-value?=?0.58], abdominal pain [16.46 % vs. 14.34 %, OR?=?1.24, 95 % CI?=?0.90–1.72, p-value?=?0.19], and pharyngitis [22.22 % vs. 18.23 %, OR?=?1.12, 95 % CI?=?0.86–1.45, p-value?=?0.40]. Excluding adverse events, all primary efficacy measures shown statistical significant result for chronic hepatitis treatment (p-value <0.05). Antiviral therapy provided significant benefit for the treatment of chronic hepatitis B with no measurable adverse effects.     

Obstructive sleep apnea increases the risk of cardiac events after percutaneous coronary intervention: a meta-analysis of prospective cohort studies

Purpose

Recent studies have shown an association between obstructive sleep apnea (OSA) and coronary artery disease; however, the association between OSA and cardiac outcomes in patients after percutaneous coronary intervention (PCI) remains undetermined.

Methods

PubMed, EMBASE, and CENTRAL were searched from inception to July 2016 for cohort studies that followed up with patients after PCI, and evaluated their overnight sleep patterns within 1 month for major adverse cardiac events (MACEs) as primary outcomes including cardiac death, non-fatal myocardial infarction (MI), and coronary revascularization and secondary outcomes including re-admission for heart failure and stroke. Outcomes data were pooled using fixed-effect meta-analysis, and heterogeneity was assessed with the I ² statistics. The methodological quality of the studies was assessed using the Newcastle-Ottawa Scale checklist, and publication bias was evaluated by a visual investigation of funnel plots.

Results

We identified seven pertinent studies including 2465 patients from 178 related articles. OSA was associated with MACEs (odds ratio [OR], 1.52, 95% confidence interval [CI], 1.20–1.93, I ² = 29%), which included cardiac death (OR 2.05, 95% CI, 1.15–3.65, I ² = 0%), non-fatal MI (OR 1.59, 95% CI, 1.14–2.23, I ² = 15%), and coronary revascularization (OR 1.69, 95% CI, 1.28–2.23, I ² = 0%). However, OSA was not associated with re-admission for heart failure (OR 1.71, 95% CI, 0.99–2.96, I ² = 0%) and/or stroke (OR 1.68, 95% CI, 0.91–3.11, I ² = 0%) according to the pooled results.

Conclusions

In patients after PCI, OSA appears to increase the risk of cardiac death, non-fatal MI, and coronary revascularization.

     

Long-term efficacy of implantable cardiac resynchronization therapy plus defibrillator for primary prevention of sudden cardiac death in patients with mild heart failure: an updated meta-analysis

Previous studies of implantable cardiac resynchronization therapy plus defibrillator (CRT-D) therapy used for primary prevention of sudden cardiac death have suggested that CRT-D therapy is less effective in patients with mild heart failure and a wide QRS complex. However, the long-term benefits are variable. We performed a meta-analysis of randomized trials identified in systematic searches of MEDLINE, EMBASE, and the Cochrane Database. Three studies (3858 patients) with a mean follow-up of 66 months were included. Overall, CRT-D therapy was associated with significantly lower all-cause mortality than was implantable cardioverter defibrillator (ICD) therapy (OR, 0.78; 95 % CI, 0.63–0.96; P = 0.02; I ² = 19 %). However, the risk of cardiac mortality was comparable between two groups (OR, 0.74; 95 % CI, 0.53–1.01; P = 0.06). CRT-D treatment was associated with a significantly lower risk of hospitalization for heart failure (OR, 0.67; 95 % CI, 0.50–0.89; P = 0.005; I ² = 55 %). The composite outcome of all-cause mortality and hospitalization for heart failure was also markedly lower with CRT-D therapy than with ICD treatment alone (OR, 0.67; 95 % CI, 0.57–0.77; P < 0.0001; I ² = 0 %). CRT-D therapy decreased the long-term risk of mortality and heart failure events in patients with mild heart failure with a wide QRS complex. However, long-term risk of cardiac mortality was similar between two groups. More randomized studies are needed to confirm these findings, especially in patients with NYHA class I heart failure or patients without LBBB.     

Effect of CPAP therapy on cardiovascular events and mortality in patients with obstructive sleep apnea: a meta-analysis

Purpose

Continuous positive airway pressure (CPAP) therapy may decrease the risk of mortality and cardiovascular events in patients with obstructive sleep apnea. However, these benefits are not completely clear.

Methods

We undertook a meta-analysis of randomized clinical trials identified in systematic searches of MEDLINE, EMBASE, and the Cochrane Database.

Results

Eighteen studies (4146 patients) were included. Overall, CPAP therapy did not significantly decrease the risk of cardiovascular events compared with the control group (odds ratio (OR), 0.84; 95 % confidence intervals (CI), 0.62–1.13; p = 0.25; I ² = 0 %). CPAP was associated with a nonsignificant trend of lower rate of death and stroke (for death: OR, 0.85; 95 % CI, 0.35–2.06; p = 0.72; I ² = 0.0 %; for stroke: OR, 0.56; 95 % CI, 0.18–1.73; p = 0.32; I ² = 12.0 %), a significantly lower Epworth sleepiness score (ESS) (mean difference (MD), ?1.78; 95 % CI, ?2.31 to ?1.24; p < 0.00001; I ² = 76 %), and a significantly lower 24 h systolic and diastolic blood pressure (BP) (for 24 h systolic BP: MD, ?2.03 mmHg; 95 % CI, ?3.64 to ?0.42; p = 0.01; I ² = 0 %; for diastolic BP: MD, ?1.79 mmHg; 95 % CI, ?2.89 to ?0.68; p = 0.001; I ² = 0 %). Daytime systolic BP and body mass index were comparable between the CPAP and control groups. Subgroup analysis did not show any significant difference between short- and mediate-to-long-term follow-up groups with regard to cardiovascular events, death, and stroke.

Conclusions

CPAP therapy was associated with a trend of decreased risk of cardiovascular events. Furthermore, ESS and BP were significantly lower in the CPAP group. Larger randomized studies are needed to confirm these findings.

     

Colchicine in addition to conventional therapy for pericarditis recurrence

Background

Randomized controlled trials (RCTs) have investigated the use of colchicine and conventional therapy for reducing the recurrence of pericarditis in patients with acute pericarditis or post-pericardiotomy syndrome. However, the benefits of these treatments are variable.

Methods

Studies were retrieved from PubMed, the Cochrane Library, and the EMBASE database.

Results

We identified nine RCTs with 1832 patients and a mean follow-up of 13.1 months. Overall, colchicine therapy significantly decreased the risk of pericarditis recurrence (odds ratio, OR 0.42; 95?% confidence interval, CI 0.33–0.52; P?<?0.001; I²?=?17.0?%). Colchicine therapy was associated with significantly lower rates of pericarditis-associated rehospitalization (OR 0.29; 95?% CI 0.16–0.53; P?<?0.0001; I²?=?0.0?%) and persistence of symptoms (OR 0.29; 95?% CI, 0.21–0.41; P?=?0.000; I²?=?0.0?%) at 72 h. Adverse events were higher in the colchicine group (relative risk, RR 1.48; 95?% CI, 1.06–2.07; P?=?0.02; I²?=?0.0?%). Subgroup analysis showed that recurrence of pericarditis was significantly lower in the colchicine therapy group, irrespective of prednisone use and the cause of pericarditis.

Conclusion

Colchicine significantly decreases the rate of pericarditis recurrence, regardless of prednisone use and the cause of pericarditis. Larger studies are needed to confirm this effect.

     

The JAK2 46/1 haplotype (GGCC) in myeloproliferative neoplasms and splanchnic vein thrombosis: a pooled analysis of 26 observational studies

Numbers of observational studies suggest that the JAK2 46/1 (GGCC) haplotype may increase the risk of myeloproliferative neoplasms (MPNs) and splanchnic vein thrombosis (SVT), but the results remain controversial. We aimed to examine the association between the JAK2 46/1 haplotype and risk of MPNs and SVT by conducting a meta-analysis. PubMed, EMBASE, Cochrane Library, CBM, and CNKI databases were searched to identify eligible studies without restrictions and by reviewing reference lists of obtained articles. Both fixed and random-effects models were used to calculate the summary risk estimates. We identified 26 observational studies of the JAK2 46/1 haplotype and risk of MPNs and SVT involving 8,561 cases and 7,434 participants. In the overall analysis, it was found that the JAK2 46/1 haplotype significantly elevated the risk of MPNs (rs10974944: C vs T: odds ratio (OR)?=?2.19, 95 % confidence interval (CI)?=?1.86–2.57, P?<?0.0001; CC vs TT: OR?=?4.63, 95 % CI?=?3.32–6.47, P?<?0.0001; CT vs TT: OR?=?2.49, 95 % CI?=?2.11–2.95, P?<?0.0001; (CC?+?CT) vs TT: OR?=?2.92, 95 % CI?=?2.51–3.39, P?<?0.0001; rs12343867: C vs T: OR?=?1.88, 95 % CI?=?1.59–2.22, P?<?0.0001; CC vs TT: OR?=?3.16, 95 %CI?=?2.14–4.65, P?<?0.0001; CT vs TT: OR?=?2.04, 95 % CI?=?1.51–2.74, P?<?0.0001; (CC?+?CT) vs TT: OR?=?2.25, 95 % CI?=?1.73–2.95, P?<?0.0001) and SVT (C vs T: OR?=?1.27, 95 % CI?=?1.06–1.52, P?=?0.011; CC vs TT: OR?=?2.33, 95 % CI?=?1.42–3.81, P?=?0.001; (CC?+?CT) vs TT: OR?=?1.25, 95 % CI?=?1.02–1.53, P?=?0.034). There was no evidence of a significant association between the rs12343867 and the risk of SVT in the genetic model (CT vs TT: OR?=?1.01, 95 % CI?=?0.80–1.29, P?=?0.906). This meta-analysis provides new evidence supporting the conclusion that the JAK2 46/1 haplotype enrichment is significantly associated with the development of MPNs and SVT in these patients.     

Clinical outcome of left ventricular multipoint pacing versus conventional biventricular pacing in cardiac resynchronization therapy: a systematic review and meta-analysis

Cardiac resynchronization therapy (CRT) is an effective treatment for selected patients with systolic heart failure. Unlike conventional biventricular pacing (BIP), the left ventricular multipoint pacing (MPP) can increase the number of left ventricular pacing sites via a quadripolar lead positioned in the coronary sinus. This synthetic study was conducted to integratively and quantitatively evaluate the clinical outcome of MPP in comparison with BIP. We systematically searched the databases of EMBASE, Ovid medline, and Cochrane Library through May 2018 for studies comparing the clinical outcome of MPP with BIP in the patients who accepted CRT. Hospitalization for reason of heart failure, left ventricular eject fraction (LVEF), CRT response, all-cause morbidity, and cardiovascular death rate was collected for meta-analysis. A total of 11 studies with 29,606 participants were included in this meta-analysis. Compared with BIP group, MPP decreased heart failure hospitalization (OR, 0.41; 95% CI, 0.33 to 0.50; P <?0.00001), improved LVEF (mean difference, 4.97; 95% CI, 3.11 to 6.83; P <?0.00001), increased CRT response (OR, 3.64; 95% CI, 1.68 to 7.87; P?=?0.001), and decreased all-cause morbidity (OR, 0.41; 95% CI, 0.26–0.66; P?=?0.0002) and cardiovascular death rate (OR, 0.21; 95% CI, 0.11–0.40; P <?0.00001). The published literature demonstrates that MPP was more effective than BIP in the heart failure patients who accepted cardiac resynchronization therapy.     

Association between susceptibility to rheumatoid arthritis and <Emphasis Type="Italic">PADI4</Emphasis> polymorphisms: a meta-analysis

The objective of the study was to determine by meta-analysis whether polymorphisms of the gene encoding peptidylarginine deiminase 4 (PADI4) are associated with susceptibility to rheumatoid arthritis (RA). A literature review was conducted to identify data sets that described analyses of genetic association between PADI4 polymorphisms and RA. Data sets were collated and a meta-analysis was performed, with a specific focus on associations within Caucasian and Asian populations. A total of 15,947 RA cases and 22,696 controls that were taken from 28 studies in 24 papers were included in this study. Meta-analysis showed a significant association between allele 2 of the PADI4_94 polymorphism and RA in the overall population (odds ratio [OR]?=?1.155, 95 % confidence interval [CI]?=?1.069–1.249, p?=?2.7?×?10^?5). Stratification by ethnicity revealed an association between PADI4_94 allele 2 and RA in Asians (OR?=?1.273, 95 % CI?=?1.193–1.359, p?<?1.0?×?10^?9), but not in Caucasians (OR?=?1.024, 95 % CI?=?0.973–1.078, p?=?0.358). However, meta-analysis using homozygote contrast showed an association between PADI4_94 allele 2 and RA in both Asians (OR?=?2.311, 95 % CI?=?1.1.858–2.875, p?<?1.0?×?10^?9) and Caucasians (OR?=?1.523, 95 % CI?=?1.157–2.004, p?=?0.008). Meta-analysis also revealed an association between allele 2 of the PADI4_104 polymorphism and RA in both Asians (OR?=?1.547, 95 % CI?=?1.247–1.919, p?=?7.1?×?10^?6) and Caucasians (OR?=?1.096, 95 % CI?=?1.025–1.172, p?=?0.008). Finally, meta-analysis showed an association between allele 2 of the PADI4_92 polymorphism and RA in Asians (OR?=?1.263, 95 % CI?=?1.153–1.384, p?=?5.8?×?10^?8), but not in Caucasians (OR?=?1.123, 95 % CI?=?0.980–1.287, p?=?0.095). Meta-analysis indicated no association between allele 2 of either the PADI4_90 or PADI4_89 polymorphisms and RA in Asians. This meta-analysis revealed that the PADI4_94 and PADI_104 polymorphisms are associated with susceptibility to RA in Asians and Caucasians, and that the PADI4_92 polymorphism is associated with susceptibility to RA in Asians, but not in Caucasians.     

Associations between <Emphasis Type="Italic">ERAP1</Emphasis> polymorphisms and susceptibility to ankylosing spondylitis: a meta-analysis

The aim of this study was to determine whether 11 polymorphisms of endoplasmic reticulum aminopeptidase 1 (ERAP1) confer susceptibility to ankylosing spondylitis (AS). The authors conducted meta-analyses on associations between ERAP1 polymorphisms and AS susceptibility by using fixed and random effects models. A total of 19 articles were included in this meta-analysis, which comprised a total of 19,902 AS patients and 39,750 controls. The meta-analysis revealed a significant association between AS and the minor alleles of the rs30187 polymorphism in all study subjects (OR?=?1.255, 95 % CI?=?1.147–1.373, P?=?8.0?×?10^?8). Stratification by ethnicity led to the identification of a significant association between this polymorphism and AS in European patients (OR?=?1.283, 95 % CI?=?1.237–1.331, P?<?1.0?×?10^?9). Meta-analyses of the results for the rs27044, rs10050860, rs2287987, rs17482078, and rs26653 polymorphisms showed the same pattern that was found for rs30187. Interestingly, the rs27037 polymorphism was significantly associated with AS susceptibility in both European and Asian patients. Meta-analysis showed a significant association between AS and the minor alleles of the rs27980 and rs27582 polymorphisms in the East Asian patients (OR?=?0.904, 95 % CI?=?0.818–0.999, P?=?0.047; OR?=?0.871, 95 % CI?=?0.772–0.982, P?=?0.024, respectively) (Table 2). However, these polymorphisms have not been studied in Europeans. This meta-analysis shows that the ERAP1 polymorphisms are associated with the development of AS in Europeans and East Asians.     

Association between high-sensitivity C-reactive protein and hyperuricemia

The aim of the study was to examine the cross-sectional association between high-sensitivity C-reactive protein (hsCRP) and hyperuricemia (HU). The hsCRP was measured by latex turbidity method. Uric acid was detected on Beckman Coulter AU 5800. HU was defined as uric acid ≥416 μmol/L for the male population and ≥360 μmol/L for the female population. A multivariable logistic analysis model was applied to test the association after adjusting for a number of potential confounding factors. A total of 1935 subjects were included in this study. According to the multivariable regression model, the relative odds of the prevalence of HU were increased by 0.56 times in the third quintile (OR 1.56, 95 % CI 1.03–2.38, P = 0.04), 0.55 times in the fourth quintile (OR 1.55, 95 % CI 1.01–2.36, P = 0.04) and 0.96 times in the fifth quintile (OR 1.96, 95 % CI 1.29–2.98, P < 0.01) of hsCRP comparing with the lowest quintile, and P for trend was smaller than 0.01. In the male population, a positive association existed in the highest quintile of hsCRP (OR 1.66, 95 % CI 1.04–2.66, P = 0.04), and P for trend was 0.07. In the female population, the multivariable-adjusted ORs (95 % CI) of HU in the fourth and fifth quintile of hsCRP were 3.02 (95 % CI 1.09–8.35, P = 0.03) and 3.66 (95 % CI 1.36–9.89, P = 0.01), respectively, and P for trend was smaller than 0.01. The findings of this cross-sectional study suggest that the hsCRP level is positively associated with the prevalence of HU. Level of evidence Cross-sectional study, Level III.     

The search for putative unifying genetic factors for components of the metabolic syndrome

Aims/hypothesis

The metabolic syndrome is a cluster of factors contributing to increased risk of cardiovascular disease and type 2 diabetes but unifying mechanisms have not been identified. Our aim was to study whether common variations in 17 genes previously associated with type 2 diabetes or components of the metabolic syndrome and variants in nine genes with inconsistent association with at least two components of the metabolic syndrome would also predict future development of components of the metabolic syndrome, individually or in combination.

Methods

Genetic variants were studied in a large prospective study of 16,143 non-diabetic individuals (mean follow-up time 23 years) from the Malmö Preventive Project. In this study, development of at least three of obesity (BMI?≥?30 kg/m²), dyslipidaemia (triacylglycerol?≥?1.7 mmol/l and/or lipid-lowering treatment), hypertension (blood pressure?≥?140/90 mmHg and/or antihypertensive medication) and hyperglycaemia (fasting plasma glucose?≥?5.6 mmol/l and/or known diabetes) was defined as development of the metabolic syndrome. The risk of developing at least three components of the metabolic syndrome or the individual components was calculated by logistic regression adjusted for age at baseline, follow-up time and sex.

Results

Polymorphisms in TCF7L2 (rs7903146, OR 1.10, 95% CI 1.04–1.17, p?=?0.00097), FTO (rs9939609, OR 1.08, 95% CI 1.02–1.14, p?=?0.0065), WFS1 (rs10010131, OR 1.07, 95% CI 1.02–1.13, p?=?0.0078) and IGF2BP2 (rs4402960, OR 1.07, 95% CI 1.01–1.13, p?=?0.021) predicted the development of at least three components of the metabolic syndrome in both univariate and multivariate analysis; in the case of TCF7L2, WFS1 and IGF2BP this was due to their association with hyperglycaemia (p?p?=?0.0033 and p?=?0.027, respectively) and for FTO it was due to its association with obesity (p?=?0.004). A polymorphism in the GCKR gene predicted dyslipidaemia (rs1260326, OR 1.15, 95% CI 1.09–1.22, p?p?p?p?

Conclusions/interpretation

Polymorphisms in susceptibility genes for type 2 diabetes (TCF7L2, WFS1, IGF2BP2) and obesity (FTO) predispose to the metabolic syndrome by increasing the risk of one specific component of the metabolic syndrome. The findings argue against a unifying genetic component for the metabolic syndrome.

     

Association between <Emphasis Type="Italic">IL17A</Emphasis> and <Emphasis Type="Italic">IL17F</Emphasis> polymorphisms and risk of Henoch–Schonlein purpura in Chinese children

Previous studies suggested that interleukin-17 and Th17 cell play an important role in the pathogenesis of childhood Henoch–Schonlein purpura (HSP). The purpose of our study is to elucidate whether the IL17A and IL17F gene polymorphisms are susceptibility genes for the development of HSP in Chinese children. A total of 148 HSP patients and 202 controls were enrolled for analyzing the single nucleotide polymorphisms (SNP) of IL17A (rs2275913, rs8193037 and rs3819025) and IL17F (rs763780 and rs9463772). TaqMan Real-Time polymerase chain reaction method was used in SNP genotyping. Compared to the healthy controls, the IL17A rs2275913 variant allele A showed a significant association with HSP [odds ratio (OR) 0.70; 95 % CI 0.51–0.94, P = 0.018]. Genotyping analysis demonstrated rs2275913 was associated with a decreased HSP risk (G/A vs. G/G: OR 0.56; 95 % CI 0.33–0.95; A/A vs. G/G: OR 0.46; 95 % CI 0.24–0.86; P = 0.032). Also, our findings showed that the A allele of IL17A rs3819025 was associated with a higher risk of HSP nephritis (OR 1.61; 95 % CI 1.00–2.58; P = 0.047). In addition, a risk haplotype of IL17A (GGA) was found (OR 1.84; 95 % CI 1.17–2.88; P = 0.008). However, no significant differences between HSP patients and healthy controls were observed when comparing genotype, allele or haplotype frequencies of the IL17F rs763780 and rs9463772 polymorphisms. In this study, we confirmed that the rs2275913 polymorphism of the IL17A gene was associated with susceptibility to HSP in Chinese children. However, there was no relationship between IL17F rs763780 and rs9463772 polymorphisms and HSP susceptibility.     

Magnetic resonance defecography versus clinical examination and fluoroscopy: a systematic review and meta-analysis

Background

Magnetic resonance defecography (MRD) allows for dynamic visualisation of the pelvic floor compartments when assessing for pelvic floor dysfunction. Additional benefits over traditional techniques are largely unknown. The aim of this study was to compare detection and miss rates of pelvic floor abnormalities with MRD versus clinical examination and traditional fluoroscopic techniques.

Methods

A systematic review and meta-analysis was conducted in accordance with recommendations from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. MEDLINE, Embase and the Cochrane Central Register of Controlled Trials were accessed. Studies were included if they reported detection rates of at least one outcome of interest with MRD versus EITHER clinical examination AND/OR fluoroscopic techniques within the same cohort of patients.

Results

Twenty-eight studies were included: 14 studies compared clinical examination to MRD, and 16 compared fluoroscopic techniques to MRD. Detection and miss rates with MRD were not significantly different from clinical examination findings for any outcome except enterocele, where MRD had a higher detection rate (37.16% with MRD vs 25.08%; OR 2.23, 95% CI 1.21–4.11, p = 0.010) and lower miss rates (1.20 vs 37.35%; OR 0.05, 95% CI 0.01–0.20, p = 0.0001) compared to clinical examination. However, compared to fluoroscopy, MRD had a lower detection rate for rectoceles (61.84 vs 73.68%; OR 0.48 95% CI 0.30–0.76, p = 0.002) rectoanal intussusception (37.91 vs 57.14%; OR 0.32, 95% CI 0.16–0.66, p = 0.002) and perineal descent (52.29 vs 74.51%; OR 0.36, 95% CI 0.17–0.74, p = 0.006). Miss rates of MRD were also higher compared to fluoroscopy for rectoceles (15.96 vs 0%; OR 15.74, 95% CI 5.34–46.40, p < 0.00001), intussusception (36.11 vs 3.70%; OR 10.52, 95% CI 3.25–34.03, p = 0.0001) and perineal descent (32.11 vs 0.92%; OR 12.30, 95% CI 3.38–44.76, p = 0.0001).

Conclusions

MRD has a role in the assessment of pelvic floor dysfunction. However, clinicians need to be mindful of the risk of underdiagnosis and consider the use of additional imaging.

     

A meta-analysis of the clinicopathological characteristics and survival outcomes of inflammatory bowel disease associated colorectal cancer

Purpose

The current study aims to use meta-analytical techniques to compare the clinicopathological characteristics and survival outcomes of inflammatory bowel disease (IBD) associated and sporadic colorectal carcinoma (CRC). Patients with IBD have an established increased risk of developing CRC. There is no consensus, however, on the clinicopathological characteristics and survival outcomes of IBD associated CRC when compared to sporadic CRC.

Methods

A comprehensive search for published studies comparing IBD associated and sporadic CRC was performed. Random effect methods were used to combine data. This study adhered to the recommendations of the MOOSE guidelines.

Results

Data were retrieved from 20 studies describing 571,278 patients. IBD associated CRC had an increased rate of synchronous tumors (OR 4.403, 95% CI 2.320–8.359; p < 0.001), poor differentiation (OR 1.875, 95% CI 1.425–2.466; p < 0.001), and a reduced rate of rectal cancer (OR 0.827, 95% CI 0.735–0.930; p = 0.002). IBD associated CRC however did not affect the frequency of T3/T4 tumors (OR 0.931, 95% CI 0.782–1.108; p = 0.421), lymph node positivity (OR 1.061, 95% CI 0.929–1.213; p = 0.381), metastasis at presentation (OR 0.970, 95% CI 0.776–1.211; p = 0.786), sex distribution (OR 0.978, 95% CI 0.890–1.074; p = 0.640), or 5-year overall survival (OR 1.105, 95% CI 0.414–2.949; p = 0.842).

Conclusions

In this large analysis of available data, IBD associated CRC was characterized by less rectal tumors and more synchronous and poorly differentiated tumors compared with sporadic cancers, but no discernable difference in sex distribution, stage at presentation, or survival could be identified.

     

Association between self-reported snoring and arterial stiffness: data from the Brisighella Heart Study

The correlation of both obstructive sleep apnoea syndrome (OSAS) and snoring with cardiovascular risk is well known, but its investigation is complex and not suitable for studying large cohorts of subjects. Thus, we prospectively evaluated 1476 non-pharmacologically treated subjects selected from the last survey of the Brisighella Heart Study. Snoring and sleep apnoea were investigated asking the subjects if they were aware of snoring during the night, and if this was associated with episodes of apnoea. A full set of clinical and laboratory parameters were evaluated, while augmentation index (AIx), and pulse wave velocity (PWV) were recorded with the Vicorder^® apparatus. A logistic regression analysis identifies as main independent predictors of AIx age (OR 1.058, 95 % CI 1.043–1.065, p < 0.001), Body Mass Index (OR 1.046, 95 % CI 1.014–1.079, p = 0.005), and apolipoprotein B (OR 1.014, 95 % CI 1.004–1.023, p = 0.001). The main independent predictors of PWV are snoring (OR 1.215, 95 % CI 1.083–1.390, p < 0.001), and snoring with apnoea (OR 1.351, 95 % CI 1.135–1.598, p = 0.014), age (OR 1.078, 95 % CI 1.052–1.089, p < 0.001), serum uric acid [SUA] (OR 1.093, 95 % CI 1.026–1.151, p < 0.001) and mean arterial pressure (OR 1.042, 95 % CI 1.024–1.056, p < 0.001). In conclusion, in our cohort of overall healthy subjects, self-reported snoring and sleep apnoea are independently associated with a higher PVW, and AIx is statistically significantly higher in snorers with or without sleep apnoea than in non-snorers. Body Mass Index and apolipoprotein B are associated with AIx, while SUA and mean arterial pressure are related to PWV.     

Heart involvement in systemic lupus erythematosus: a systemic review and meta-analysis

Cardiovascular diseases are one of the most important causes of the disability and mortality in patients with systemic lupus erythematosus (SLE). The present study examined the cardiac abnormalities in patients with SLE by echocardiography. Case-control studies were obtained by searching PubMed MEDLINE, Embase, and MD Consult. Systemic review and meta-analysis were performed to assess the cardiac abnormalities based on the changes in the echocardiography in patients with SLE. Twenty-two studies including 1117 SLE patients and 901 healthy controls were enrolled into this study. We found that patients with SLE developed the pericardial effusion (odds ratio (OR) (95 % confidence interval (CI)) 30.52 (9.70–96.02); p < 0.00001) and the combined valvular alterations (OR (95 %CI) 11.08 (6.98–17.59); p < 0.00001). In addition, SLE patients also exhibited an increase in the left atrial diameter (LAD) (WMD—weighted mean difference (95 %CI) 0.18 (0.06–0.29); p = 0.002), the left ventricular internal diameter in diastole (LVDd) (WMD (95 %CI) 0.07 (0.02–0.12); p = 0.01), and the left ventricular mass index (LVMI) (WMD (95 %CI) 5.69 (2.69–8.69); p = 0.0002). In contrast, the left ventricular systolic function (WMD (95 %CI) ?1.22 (?1.69 to ?0.75); p < 0.00001) and diastolic function including E/A ratio and E/E’ ratio (WMD (95  % CI) ?0.13 (?0.24 to ?0.01); p = 0.04; WMD (95  % CI) 1.71 (0.43 to 2.99); p = 0.009) were decreased in SLE patients. Patients with SLE are associated with significant alterations in cardiac structure and function as demonstrated by echocardiography. Data from this study suggest that echocardiographic assessment should be considered as a part of routine examinations for SLE patients clinically.