Isoprostane in systemic sclerosis: A systematic review and meta-analysis

Abstract

Objectives: To further the knowledge of oxidative stress in systemic sclerosis (SSc), we performed a systematic review and meta-analysis on studies measuring isoprostane, a vasoactive agent deriving from arachidonic acid and implicated in the vasculopathy of SSc.

Methods: Systematic search following the PRISMA guidelines in PubMed and EMBASE between January-1990/December-2017 using the terms: oxidative stress, isoprostane, systemic sclerosis and scleroderma.

Results: After the screening process, 8 studies including 240 SSc patients and 192 controls were included in the systematic review and meta-analysis, 6 investigating urinary and 2 serum isoprostane: random effect meta-analysis revealed isoprostane overgeneration in SSc (p?<?.001) with wide heterogeneity (I²?=?75%). Subgroup analysis on urinary isoprostane favoured excess excretion in SSc (p?=?.009) with slightly lower heterogeneity (I²?=?67%); further subgroup analysis according to unit of measurement revealed no increased isoprostane excretion when expressed as pg/mg creatinine but increased when expressed as pmol/mmol creatinine (p?=?.05) with medium heterogeneity (I²?=?32%). Subgroup analysis on serum isoprostane favoured overproduction in SSc (p?<?.0001) with no heterogeneity.

Conclusion: There is some evidence for isoprostane overgeneration in SSc that confirms the occurrence of oxidative stress in this setting: further prospective studies with specified outcomes are needed to evaluate the prognostic value of this functional biomarker.     

Number of parity and the risk of non-Hodgkin lymphomas: a dose–response meta-analysis of observational studies

Background: Epidemiological reports have shown that parity is associated with a risk of developing non-Hodgkin lymphomas (NHL). However, the findings have been inconsistent.

Methods: We searched the EMBASE and PubMed databases for eligible studies up to 10 March 2016. Category and generalized least square regression models were used to perform data analyses.

Results: In total, five cohort and seven case–control studies were identified. Categorical analyses indicated that parity number has little association with NHL and its subtypes. In dose–risk analyses, there were no relationships between parity and NHL risk (p_{for association}?=?0.064; n?=?10). The summarized risk ratio (RR) was 0.97 (95% confidence interval (CI): 0.95–1.00; I²?=?57.8%; p_{heterogeneity}?=?0.014; Power?=?0.79) for each additional live birth increase. Similarly, for B-cell NHL, there was a null association between parity and NHL risk (p_{for association}?=?0.121; n?=?5). The combined RR was 0.96 (95% CI?=?0.90–1.03; I²?=?63.7%; p_{heterogeneity}?=?0.026; Power?=?0.71) for each additional live birth. For follicular NHL, there was still a non-significant association identified (p_{for association}?=?0.071; n?=?4), the pooled RR was 1.00 (95% CI?=?0.95–1.07; I²?=?17.3%; p_{heterogeneity}?=?0.305; Power?=?0.26) per additional live birth.

Conclusions: Our data identified little evidence suggesting that high parity is a protective factor against the development of NHL, including its B-cell and follicular subtypes.     

Tobacco smoking and the risk of pancreatitis: A systematic review and meta-analysis of prospective studies

BackgroundTobacco smoking has been associated with increased risk of pancreatitis in several studies, however, not all studies have found an association and it is unclear whether there is a dose-response relationship between increasing amount of tobacco smoked and pancreatitis risk. We conducted a systematic review and meta-analysis of prospective studies on tobacco smoking and pancreatitis to clarify the association.MethodsPubMed and Embase databases were searched for relevant studies up to April 13th^, 2019. Prospective studies that reported adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) for the association between tobacco smoking and pancreatitis were included and summary RRs were calculated using a random effects model.ResultsTen prospective studies were included. The summary RR for acute pancreatitis was 1.49 (95% CI: 1.29–1.72, I² = 68%, n = 7) for current smokers, 1.24 (95% CI: 1.15–1.34, I² = 0%, n = 7) for former smokers, and 1.39 (95% CI: 1.25–1.54, I² = 69%, n = 7) for ever smokers compared to never smokers. Similar results were observed for chronic pancreatitis and acute/chronic pancreatitis combined. The summary RR per 10 cigarettes per day was 1.30 (95% CI: 1.18–1.42, I² = 42%, n = 3) and per 10 pack-years in current smokers was 1.13 (95% CI: 1.08–1.17, I² = 14%, n = 4) for acute pancreatitis and results were similar for chronic pancreatitis and acute/chronic pancreatitis combined.ConclusionsThese results suggest that tobacco smoking increases the risk of acute and chronic pancreatitis and acute and chronic pancreatitis combined and that there is a dose-response relationship between increasing number of cigarettes and pack-years and pancreatitis risk.     

Safety and efficacy of Ofatumumab in chronic lymphocytic leukemia: a systematic review and meta-analysis

Objectives: Increasing numbers of clinical studies have been carried out to investigate the therapeutic effect of Ofatumumab for patients with chronic lymphocytic leukemia (CLL) but no studies have yet reported a pooled estimate of the treatment effect. We performed a meta-analysis of evidence from 13 clinical trials to assess effectiveness and safety of Ofatumumab-based therapy in patients with CLL.

Methods: Relevant publications from PubMed, Web of Science, Embase, and ClinicalTrials.gov were searched. The primary efficacy outcomes were progression-free survival (PFS) and overall survival (OS). The second endpoint was the adverse events.

Results: The pooled efficacy analysis showed that there were no significant difference in PFS [hazard ratios (HR)?=?0.88, 95% confidence interval (CI)?=?0.47–1.63, p?=?0.677, I²?=?94.9%] and OS (HR?=?0.97, 95% CI?=?0.70–1.36, p?=?0.878, I²?=?58.7%) between Ofatumumab-based therapy and non-Ofatumumab therapy. The pooled toxicity analysis showed that Ofatumumab-based therapy was associated with an increased risk of infusion-related reaction but decreased risk of thrombocytopenia and anemia compared with non-Ofatumumab-based therapy. Moreover, infections, and infusion-related reaction occurred more frequently in participants with single Ofatumumab studies.

Discussion: Our analysis showed PFS was statistically significantly improved with Ofatumumab-based treatments (including Ofatumumab alone, Ofatumumab plus chemotherapy) for CLL compared with observation or chemotherapy-based regimen groups. Ofatumumab had no statistically significant improvement on the OS of patients with CLL. The Ofatumumab-based therapy could generally decrease the risk of adverse effects except infusion-related reaction and infections.     

Is elective cesarean section associated with a higher risk of asthma? A meta-analysis

Abstract

Background: Recent meta-analyses indicate that children delivered by cesarean section have increased risk for asthma. However, the studies included in these previous meta-analyses showed significant heterogeneity. Furthermore, no previous meta-analysis has distinguished the association of elective and emergency CS, spontaneous and instrumental vaginal deliveries (VD) with the odds of asthma. Objective: To examine the association between specific mode of delivery and the prevalence of asthma. Methods: PUBMED, Google Scholar, EMBASE, and MEDLINE were searched to identify relevant studies. Odds ratio (OR) and 95% confidence interval (CI) were calculated from the prevalence of asthma in children born by elective CS, emergent CS, instrumental VD and spontaneous VD. Meta-analysis was then used to derive a combined OR. Heterogeneity between studies was also tested in the findings. Results: A total of 26 studies were identified. The overall meta-analysis revealed an increase in the risk of asthma in children delivered by CS (OR?=?1.16, 95% CI 1.14, 1.29), and no evidence of heterogeneity was found (I²?=?24.6%). Elective and emergency CS moderately increased the risk of asthma (OR?=?1.21, 95% CI 1.17, 1.25; I²?=?39.9%; OR?=?1.23, 95% CI 1.19–1.26). The risk of asthma was also higher in the children born by instrumental VD (OR?=?1.07, 95% CI, 1.04–1.11) but with evidence of heterogeneity (I²?=?54.9%). Conclusion: About 20% increase in the subsequent risk of asthma was both found in children delivered by elective and emergency CS. The increasing rates of CS worldwide might partly explain the concomitant rise in asthma during the same time period.     

Cancer-risk by family history and mismatch-repair mutation in Lynch syndrome

Abstract

Introduction: Surveillance of Lynch syndrome (LS) is recommended to reduce cancer-risk. There is an increased awareness that cancer-risk may vary with mismatch-repair mutation and family history. However, gene-specific and family-specific surveillance are not recommended. Therefore, we aimed to estimate the cumulative incidence of lesions and to assess the cancer-risk by family history and mismatch-repair mutation (MMR).

Methods: Single-centre retrospective cohort of all individuals (n?=?241) in a specialized institution was conducted.

Results: Forty-eight percent of individuals inherited MSH2 mutations, 32% MLH1, 15% MSH6 and 5% PMS2. The calculated cumulative incidence for any cancer increased with age. By age 70, the cumulative incidence for low-risk, high-risk adenomas and CRC was estimated at 66.6%, 57.7% and 25.7%, respectively. By age 70, the cumulative incidence of endometrial cancer (EC), gastric cancer and urinary tract cancer was estimated at 17.3%, 3.3% and 12.6%, respectively. MLH1 and MSH2 mutation carriers had lower mean age of CRC diagnosis than MSH6 and PMS2 [MLH1:44(CI95% 38–50); MSH2:43(CI95% 40–47); MSH6:52(CI95% 45–59); PMS2:46(CI95% 35–57)]. The risk of EC was higher when family history was present (RR = 2.39, CI95%[1.3;4.6]). MSH6 mutation carriers had higher risk of EC comparative to other MMR mutation carriers (RR = 1.9, p?=?.09). The risk of urinary tract cancer was higher with MSH2 (RR = 8.4, CI95%[2.7;25.9]) and positive family history (RR = 10.8, CI95%[1.4;82.8]).

Conclusion: This cohort demonstrates the effectiveness of LS surveillance and suggests possible tailored surveillance strategies by gene mutation and family history.     

The association between different hormone replacement therapy use and the incidence of lung cancer: a systematic review and meta-analysis

BackgroundMany peri- and postmenopausal women use hormone replacement therapy (HRT) to relieve menopausal symptoms. However, the side effects of different HRT use (ever/current/former vs. never HRT use) on lung cancer risk in women were not completely consistent. Thus, we conducted this meta-analysis to examine the connection between current, former or ever HRT use and the incidence of lung cancer among women.MethodsWe systematically searched the PubMed, Web of Science, EMBASE, Cochrane Library, SCOPUS, China National Knowledge Infrastructure, Wanfang and VIP databases to identify relevant articles published from the inception of the respective databases to February 18, 2022. On the relationship between different HRT use and the incidence of lung cancer among women. Relevant risk estimates [relative risks (RRs), odds ratio (OR)] were combined based on specific study types. The Newcastle-Ottawa Scale was used to evaluate the quality of included studies. This analysis has been registered in the International prospective register of systematic reviews (PROSPERO; CRD42020219728). Publication bias was tested based on Egger’s and Begg’s tests.ResultsA total of 22 studies (13 prospective cohort studies and 9 case-control studies) were included, comprising 911,194 participants and 17,329 patients. Compared to never HRT users, in pooled cohort studies, current HRT users had a statistically decreased risk of lung cancer [RR 0.91, 95% confidence interval (CI): 0.86–0.97, I²=22.9%], and similar results were found among the postmenopausal women with current HRT use (RR 0.91, 95 CI: 0.85–0.98, I²=36%), while in pooled case-control studies, ever HRT users had a decreased risk of incidence of lung cancer [odds ratio (OR) 0.75, 95% CI: 0.69–0.81, I²=0%] as did female non-smokers with ever HRT use (OR 0.76, 95% CI: 0.66–0.87, I²=36.8%).ConclusionsCurrent or ever HRT use is partly correlated with the decreased incidence of lung cancer in women. Concerns about the incidence of lung cancer can be reduced when perimenopausal and postmenopausal women use current HRT to reduce menopausal symptoms. Meanwhile, given the roles of hormone receptors and relevant genes single nucleotide polymorphism (SNPs) among females, HRT use should be cautiously administered and individualized.     

Impact of obstructive sleep apnea-related symptoms on surgical wound complications in breast cancer patients: pilot study in a tertiary health center in Turkey

Purpose

Wound healing is an important factor influencing morbidity following surgical procedures. The association of obstructive sleep apnea (OSA) with numerous postoperative complications has been previously reported. In this study, we report the impact of OSA-related symptoms on wound complications in breast cancer patients in the postoperative period.

Methods

Breast cancer patients were enrolled for a prospective observational study. Outcome measures included sociodemographic data, self-reported sleep-wake questionnaires (Berlin questionnaire, STOP-BANG, and Epworth sleepiness scale [ESS]) as well as type of surgery, smoking status, duration of anesthesia, the need for postoperative opioid drugs, and complications for surgical wounds. Patients’ general preoperative health status was quantified by using American Society of Anesthesiologists (ASA) scores.

Results

A total of 132 women were included in the study, of whom 61% (n?=?81) underwent mastectomy, and 39% (n?=?51) had breast conserving surgery. Mean ESS score of the study group was 7.7?±?0.5. Multivariant analysis identified, either being at medium high risk by STOP-BANG questionnaire (OR:1.77, p: 0.04) or being at high risk by Berlin questionnaire (OR:1.96, p: 0.04) as well as high BMI (OR:2.76 95% CI:1.73–4.65, p: 0.02), smoking history (OR:3.04 95% CI: 2.25–3.86, p: 0.01) and type of surgery (OR:2.64 95% CI: 1.63–2.89, p: 0.03) were independent factors for wound healing.

Conclusions

The study results suggest that patients with high risk for OSA have a tendency to develop postoperative wound complications after breast cancer surgery. This study lays groundwork for further scrutiny using more robust methodology.

     

Relationship between cigarette smoking and risk of chronic myeloid leukaemia: a meta-analysis of epidemiological studies

Objective: Previous epidemiologic studies that have been reported on the association between cigarette smoking and risk of chronic myeloid leukaemia (CML) have remained controversial. A comprehensive meta-analysis was performed to evaluate smoking as a potential relationship factor and incidence of CML.

Methods: Systematic literatures collected from articles published before August 2015 were searched from PubMed, EMBASE and the Cochrane Library. A total of 10 studies (nine case–controls and one cohort) met inclusion criteria of this meta-analysis. Odds ratios (ORs) with 95% confidence interval (CI) were calculated to assess the strength of the association between cigarette smoking and risk of CML in this study. Quality assessments were performed on the studies with the Newcastle-Ottawa Scale. I2 index was used to evaluate heterogeneity. Finally, publication bias was assessed through funnel plots and Begger’s test.

Results: No significant association was observed between ever-smokers and CML when compared among non-smokers (OR?=?1.13, 95% CI: 0.99–1.29) or between subgroups stratified by smoking history, gender, geographical region, study design and source of patients. Our results demonstrate that this association was stronger in individuals who smoked <20 cigarettes/day (OR?=?1.72, 95% CI: 1.06–2.79) vs. individuals who smoked >20 cigarettes/day (OR?=?1.24, 95% CI: 0.55–2.81). Moreover, cumulative smoking of <15, 15–30 and >30 pack-years was associated with ORs of 1.22, 1.32 and 1.39, respectively (P?Conclusion: This meta-analysis suggests that smoking may significantly increase the risk of CML in a dose-dependent manner. However, additional well-designed, prospective cohort studies are required to verify these findings and identify other risk factors associated with CML.     

Meta‐analysis of alcohol consumption and risk of extrahepatic bile system cancer

Aim: Alcohol consumption increases the risk of liver cancer. However, there is still controversy regarding alcohol consumption and the risk of extrahepatic bile system cancer (EBSC). We performed a meta‐analysis to provide an overview of the relevant studies and gain more robust estimates of the relationship between alcohol consumption and risk of EBSC. Methods: Relevant studies published between January 1966 and October 2010 were identified by searching Medline, Embase and the Cochrane Library. Studies were selected using a priori defined criteria. The strength of the relationship between alcohol consumption and risk of EBSC was assessed by adjusted odds ratio (OR). Results: A total of 113 767 participants from 10 studies (nine case–control studies and one cohort study) were identified in this meta‐analysis. The studies provided adjusted overall OR estimates for drinkers versus non‐/low drinkers, leading to a pooled adjusted OR of 0.82 (95% confidence interval [CI] = 0.72–0.94, P for heterogeneity = 0.194, I² = 27.2%). The overall adjusted OR of hospital‐based studies and population‐based studies were 0.80 (95% CI = 0.65–0.99, P = 0.260) and 0.79 (95% CI = 0.64–0.98, P = 0.119), respectively. For the heavy drinkers, the adjusted OR significance increased to 1.58 (95% CI = 0.97–2.57, P for heterogeneity = 0.055, I² = 65.4%), but it had no statistical significance. Conclusion: There is evidence that moderate alcohol consumption lowers the risk of EBSC compared with non‐/low alcohol consumption, but not heavy alcohol consumption. Further multicenter and better controlled studies are required to confirm these findings.     

The incidence and outcomes from Clostridium difficile infection in hospitalized adults with inflammatory bowel disease

Objectives: Clostridium difficile infection (CDI) may worsen outcomes in patients with inflammatory bowel disease (IBD), but large database-driven studies have conflicting results. The study objective is to analyze clinical features and outcomes in patients with CDI and IBD using the National Hospital Discharge Survey (NHDS) database from 2005 to 2009.

Materials and methods: NHDS collects the clinical information on patients dismissed from non-Federal short-stay United States hospitals. CDI and IBD patients were identified using ICD-9 codes. Demographics, diagnoses, procedures, length of stay (LOS) and dismissal information were abstracted.

Results: Of an estimated 162 million hospitalizations; 5.62?×?10⁵ were for IBD (0.35%); 53.2% were female. CDI developed in 3.7% of hospitalized IBD patients as compared to 0.78% of all adults (OR, 3.9; 95% CI, 3.3–4.6; p?p?p?p?p?Conclusions: CDI in IBD patients prolonged hospitalization and increased in-hospital mortality and likelihood of dismissal to a care-facility as compared to IBD patients without CDI. CDI was more common among African-American IBD patients compared to IBD patients of other races.     

Breastfeeding and the maternal risk of type 2 diabetes: A systematic review and dose–response meta-analysis of cohort studies

Background and aimsBreastfeeding has been associated with reduced risk of maternal type 2 diabetes in some cohort studies, but the evidence from published studies have differed with regard to the strength of the association. To clarify this association we conducted a systematic review and dose–response meta-analysis of breastfeeding and maternal risk of type 2 diabetes.Methods and resultsWe conducted a systematic review and dose–response meta-analysis of prospective studies of breastfeeding and maternal risk of type 2 diabetes. We searched the PubMed, Embase and Ovid databases up to September 19th 2013. Summary relative risks were estimated using a random effects model. Six cohort studies including 10,842 cases among 273,961 participants were included in the meta-analysis. The summary RR for the highest duration of breastfeeding vs. the lowest was 0.68 (95% CI: 0.57–0.82, I² = 75%, p_{heterogeneity} = 0.001, n = 6). The summary RR for a three month increase in the duration of breastfeeding per child was 0.89 (95% CI: 0.77–1.04, I² = 93%, p_{heterogeneity} < 0.0001, n = 3) and the summary RR for a one year increase in the total duration of breastfeeding was 0.91 (95% CI: 0.86–0.96, I² = 81%, p_{heterogeneity} = 0.001, n = 4). There was little difference in the summary estimates whether or not BMI had been adjusted for. The inverse associations appeared to be nonlinear, p_nonlinearity < 0.0001 for both analyses, and in both analyses the reduction in risk was steeper when increasing breastfeeding from low levels.ConclusionThis meta-analysis suggests that there is a statistically significant inverse association between breastfeeding and maternal risk of type 2 diabetes.     

Diabetes mellitus,blood glucose and the risk of atrial fibrillation: A systematic review and meta-analysis of cohort studies

Background

Diabetes and elevated blood glucose have been associated with increased risk of atrial fibrillation in a number of epidemiological studies, however, the findings have not been entirely consistent. We conducted a systematic review and meta-analysis to clarify the association.

Contrast-induced acute kidney injury and adverse clinical outcomes risk in acute coronary syndrome patients undergoing percutaneous coronary intervention: a meta-analysis

Background

Recent studies have shown associations between contrast-induced acute kidney injury (CI-AKI) and increased risk of adverse clinical outcomes in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI); however, the estimates are inconsistent and vary widely. Therefore, this meta-analysis aimed to evaluate the precise associations between CI-AKI and adverse clinical consequences in patients undergoing PCI for ACS.

Methods

EMBASE, PubMed, Web of Science? and Cochrane Library databases were systematically searched from inception to December 16, 2016 for cohort studies assessing the association between CI-AKI and any adverse clinical outcomes in ACS patients treated with PCI. The results were demonstrated as pooled risk ratios (RRs) with 95% confidence intervals (CI). Heterogeneity was explored by subgroup analyses.

Results

We identified 1857 articles in electronic search, of which 22 (n?=?32,781) were included. Our meta-analysis revealed that in ACS patients undergoing PCI, CI-AKI significantly increased the risk of adverse clinical outcomes including all-cause mortality (18 studies; n?=?28,367; RR?=?3.16, 95% CI 2.52–3.97; I²?=?56.9%), short-term all-cause mortality (9 studies; n?=?13,895; RR?=?5.55, 95% CI 3.53–8.73; I²?=?60.1%), major adverse cardiac events (7 studies; n?=?19,841; RR?=?1.49, 95% CI: 1.34–1.65; I² =?0), major adverse cardiovascular and cerebrovascular events (3 studies; n?=?2768; RR?=?1.86, 95% CI: 1.42–2.43; I² =?0) and stent restenosis (3 studies; n?=?130,678; RR?=?1.50, 95% CI: 1.24–1.81; I² =?0), respectively. Subgroup analyses revealed that the studies with prospective cohort design, larger sample size and lower prevalence of CI-AKI might have higher short-term all-cause mortality risk.

Conclusions

CI-AKI may be a prognostic marker of adverse outcomes in ACS patients undergoing PCI. More attention should be paid to the diagnosis and management of CI-AKI.

     

Acute Kidney Injury Following Transcatheter Edge-to-Edge Mitral Valve Repair: A Systematic Review and Meta-Analysis

BackgroundAim of this study was to perform a systematic review a meta-analysis of the literature in order to identify predictors of acute kidney injury (AKI) in patients with mitral regurgitation (MR) undergoing transcatheter edge-to-edge repair (TEER) and assess its effect on in-hospital outcomes and mortality. Although iodinated contrast is not typically used in TEER, these patients are still at risk for developing AKI.MethodsStudies reporting on the effect of incident AKI on mortality following TEER for MR were included. Random-effects meta-analysis was performed, comparing clinical outcomes between the patients with or without incident AKI.ResultsSix studies including a total of 2057 patients (377 AKI and 1680 No-AKI) were included and analyzed. AKI was significantly associated with 30-day mortality after TEER (Odds ratio (OR): 8.06; 95% CI: 3.20, 20.30, p < 0.01; I² = 18.4%) and all-cause mortality over a mean follow-up time of 30 months (Hazard ratio (HR): 2.48; 95% CI: 1.89, 3.24, p < 0.01; I² = 23.7%). AKI after TEER was associated with prolonged hospitalization (Mean difference (in days): 1.41; 95% CI: 0.52, 2.31, p < 0.01; I² = 82.4%). Stage 4 chronic kidney disease (CKD), device failure and history of chronic obstructive pulmonary disease (COPD) were significant predictors of AKI following TEER (CKD stage 4: OR: 2.38; 95% CI: 1.18, 4.78, p = 0.02; I² = 0.0%; Device failure: OR: 3.15; 95% CI: 1.94, 5.12, p < 0.01; I² = 0.0%; COPD: OR: 1.92; 95% CI: 1.16, 3.17; I² = 26.7%).ConclusionsOur findings highlight the renal vulnerability of the TEER population to renal injury and the associated deterioration in clinical outcomes and survival.     

Fibroblast growth factor 21 in cardio-metabolic disorders: a systematic review and meta-analysis

BackgroundFibroblast growth factor 21 is a signalling protein involved in cell differentiation, morphogenesis, proliferation and metabolism. Recent studies have associated increased levels of FGF21 in the development of cardiovascular diseases, whereas others have reported no significant associations. Therefore, this systematic review and meta-analysis evaluated the value in predicting the risk of cardio-metabolic disorders and mortality.MethodsPubMed and EMBASE were searched until 5th September 2017 for studies that evaluated the roles of FGF21 levels in cardio-metabolic disorders.ResultsA total of 183 and 301 entries were retrieved; 24 studies met the inclusion criteria. Four studies were identified by an additional search. Therefore, 28 studies were included in the final meta-analysis. High FGF21 levels significantly predicted the incidence of coronary artery disease (hazard ratio [HR]: 1.29; 95% confidence interval [CI]: 1.06–1.55; P < 0. 01; I² = 48%) and the risk of metabolic syndrome (HR: 1.70, 95% CI: 1.35–2.15; P < 0.0001 I² = 24%). In diabetes mellitus, FGF21 predicted disease incidence or progression (HR: 1.35, 95% CI: 1.06–1.72, P < 0.05, I² = 69%) and worsening renal failure (HR: 1.06, 95% CI: 1.03–1.09, P < 0.0001, I² = 47%). FGF21 also predicted all-cause mortality (HR: 3.00, 95% CI: 1.23–7.33; P < 0.05; I² = 51%), and cardiovascular mortality (HR: 2.33, 95% CI: 1.08–4.99, P < 0.05, I² = 75%).ConclusionFGF21 significantly predicts the incidence of coronary artery disease, the risks of metabolic syndrome, diabetes mellitus and renal progression in diabetes. It also predicted all-cause and cardiovascular mortality.     

Coffee or tea consumption and the risk of rheumatoid arthritis: a meta-analysis

The aim of this study was to analyze published results for an association between coffee or tea intake and the development of rheumatoid arthritis (RA). We investigated the evidence for a relationship between coffee or tea consumption and the development of RA by performing a meta-analysis of the published results. Five studies (three cohort and two case–control studies) including 134,901 participants (1,279 cases of RA and 133,622 noncases) were considered in the meta-analysis. Meta-analysis of the cohort studies revealed a trend of an association between total coffee intake and RA incidence (relative risk [RR] of the highest versus the lowest group?=?4.148, 95 % confidence interval [CI]?=?0.792–21.73, p?=?0.092). Meta-analysis of case–control studies showed a significant association between total coffee intake and RA incidence (RR?=?1.201, 95 % CI?=?1.058–1.361, p?=?0.005). Combining the data of the cohort and case–control studies showed a significant association between total coffee intake and RA incidence (RR?=?2.426, 95 % CI?=?1.060–5.554, p?=?0.036). Meta-analysis stratified by seropositivity indicated a significant association between coffee consumption and seropositive RA risk (RR?=?1.329, 95 % CI?=?1.162–1.522, p?=?3.5?×?10^?5), but not seronegative RA risk (RR?=?1.093, 95 % CI?=?0.884–1.350, p?=?0.411). No association was found between tea intake and RA incidence (RR?=?0.880, 95 % CI?=?0.624–1.239, p?=?0.463). This meta-analysis of 134,901 participants (most of the participants were controls) suggests that high coffee consumption is associated with an elevated risk of RA development. The association between coffee and RA was found in seropositive RA, but not in seronegative RA.     

Plasma levels of angiopoietin-2, VEGF-A,and VCAM-1 as markers of bevacizumab-induced hypertension: CALGB 80303 and 90401 (Alliance)

Hypertension is a common toxicity induced by bevacizumab and other antiangiogenic drugs. There are no biomarkers to predict the risk of bevacizumab-induced hypertension. This study aimed to identify plasma proteins related to the function of the vasculature to predict the risk of severe bevacizumab-induced hypertension. Using pretreated plasma samples from 398 bevacizumab-treated patients in two clinical trials (CALGB 80303 and 90401), the levels of 17 proteins were measured via ELISA. The association between proteins and grade 3 bevacizumab-induced hypertension was performed by calculating the odds ratio (OR) from logistic regression adjusting for age, sex, and clinical trial. Using the optimal cut-point of each protein, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for hypertension were estimated. Five proteins showed no difference in levels between clinical trials and were used for analyses. Lower levels of angiopoietin-2 (p?=?0.0013, OR 3.41, 95% CI 1.67–7.55), VEGF-A (p?=?0.0008, OR 4.25, 95% CI 1.93–10.72), and VCAM-1 (p?=?0.0067, OR 2.68, 95% CI 1.34–5.63) were associated with an increased risk of grade 3 hypertension. The multivariable model suggests independent effects of angiopoietin-2 (p?=?0.0111, OR 2.71, 95% CI 1.29–6.10), VEGF-A (p?=?0.0051, OR 3.66, 95% CI 1.54–9.73), and VCAM-1 (p?=?0.0308, OR 2.27, 95% CI 1.10–4.92). The presence of low levels of 2–3 proteins had an OR of 10.06 (95% CI 3.92–34.18, p?=?1.80?×?10^–5) for the risk of hypertension, with sensitivity of 89.7%, specificity of 53.5%, PPV of 17.3%, and NPV of 97.9%. This is the first study providing evidence of plasma proteins with potential value to predict patients at risk of developing bevacizumab-induced hypertension.

Clinical trial registration: ClinicalTrials.gov Identifier: NCT00088894 (CALGB 80303); and NCT00110214 (CALGB 90401).

     

The risk of developing a mismatch repair deficient colorectal cancer after undergoing cholecystectomy

Objectives: Mismatch repair deficient (dMMR) colorectal cancer (CRC) is caused by inactivation of the MMR DNA repair system, most commonly via epigenetic inactivation of the MLH1 gene, and these tumors occur most frequently in the right colon. The objective was to determine whether cholecystectomy (CCY) increases the risk of a dMMR CRC by comparing CCY incidence in patients with dMMR CRC and proficient MMR (pMMR) CRC to unaffected controls.

Materials and methods: All patients diagnosed with CRC in Iceland from 2000 to 2009 (n?=?1171) were included. They had previously been screened for dMMR by immunohistochemistry (n?=?129 were dMMR). Unaffected age- and sex-matched controls (n?=?17,460) were obtained from large Icelandic cohort studies. Subjects were cross-referenced with all pathology databases in Iceland to establish who had undergone CCY. Odds ratios were calculated using unconditional logistic regression.

Results: Eighteen (13.7%) dMMR CRC cases and 90 (8.7%) pMMR CRC cases had undergone CCY compared to 1532 (8.8%) controls. CCY-related odds ratios (OR) were 1.06 (95% CI 0.90–1.26, p?=?.577) for all CRC, 1.16 (95% CI 0.66–2.05 p?=?.602) for dMMR CRCand 1.04 (95% CI 0.83–1.29, p?=?.744) for pMMR CRC. Furthermore, OR for dMMR CRC was 0.51 (95% CI 0.16–1.67, p?=?.266), 2.04 (95% CI 0.92–4.50, p?=?.080) and 1.08 (95% CI 0.40–2.89, p?=?.875)?<10 years, 10–20 years and?>20 years after a CCY, respectively.

Conclusions: There was no evidence of increased risk of developing dMMR CRC after CCY although a borderline significantly increased 2-fold risk was observed 10–20 years after CCY. Larger studies are warranted to examine this further.     

Biliary tract malignancies: a population-based study on incidence,prognosis and management of patients

Background: Biliary tract malignancies are uncommon and few population-based studies are available.

Methods: This nationwide population-based study in Iceland included all patients diagnosed with intra- and extrahepatic cholangiocarcinoma, gallbladder and ampullary cancer from 1984 to 2012. Patients were identified through the Icelandic Cancer Registry. Clinical information was obtained from patient records.

Results: Overall 245 patients were identified: 38 had intrahepatic cholangiocarcinoma, 66 extrahepatic cholangiocarcinoma, 73 gallbladder cancer (GBC) and 68 ampullary cancer. Overall incidence for bile tract malignancies was 1–3 per 100,000 person-years and less than 1 by sub-type. The overall bile tract malignancies in males increased from 1.3 (95% CI 0.8–1.8) to 2.5 (1.9–3.1) per 100,000 inhabitants. The incidence of GBC among females decreased from 1.1 (0.7–1.5) to 0.5 (0.2–0.7). Surgery decreased for extrahepatic cholangiocarcinoma (56 to 23%, p?=?.027), ampullary cancer (80 to 48%, p?=?.03) and overall bile tract cancer (61 to 32%, p?p?Conclusions: Overall incidence of bile tract malignancies increased in males and GBC decreased in women. Long-term survival is poor and did not improve despite changes in treatment.