The relationship between factor V Leiden, prothrombin G20210A, and MTHFR mutations and the first major thrombotic episode in polycythemia vera and essential thrombocythemia

Arterial and venous thrombosis are the most frequent complications in patients with polycythemia vera and essential thrombocythemia. We sought to demonstrate a possible contribution of the factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) 677 C?>?T and 1298 A?>?C mutations to the thrombotic risk in patients with polycythemia vera and essential thrombocythemia along with other biological features of these patients. We included 86 patients with polycythemia vera, of which 34 (39.5 %) had major thrombosis and 95 patients with essential thrombocythemia, of which 22 (23.1 %) had major thrombosis. In the whole cohort of patients, only the factor V Leiden mutation was significantly associated with both arterial and venous thrombosis in univariate and multivariate analysis (odds ratio (OR)?=?4.3; 95 % confidence interval (CI)?=?1.5–12.5; p?=?0.008 and OR?=?4.3; 95 % CI?=?1.2–15.9; p?=?0.02, respectively). Other factors significantly associated with thrombosis in both univariate and multivariate analysis were male sex (OR?=?2.8, 95 % CI?=?1.4–5.4, p?=?0.002 and OR?=?3.5, 95 % CI?=?1.6–7.6, p?=?0.002, respectively) and the JAK2 V617F mutation (OR?=?5.5, 95 % CI?=?2.1–15, p?=?0.0001 and OR?=?6.9, 95 % CI?=?2.2–21.2, p?=?0.001, respectively). In conclusion, among the four mutations analyzed (factor V Leiden, prothrombin G20210A, and MTHFR 677 C?>?T and 1298 A?>?C), only factor V Leiden is a major contributor to thrombosis in polycythemia vera and essential thrombocythemia.     

A novel scoring system to predict the incidence of invasive fungal disease in salvage chemotherapies for malignant lymphoma

The requirement of antifungal prophylaxis has not been established in the chemotherapies for malignant lymphoma. This study was conducted to explore the incidence of invasive fungal diseases (IFD) and their risk factors in patients receiving salvage therapies for malignant lymphoma. We retrospectively analyzed 177 consecutive patients who received these therapies (705 courses in total) at our institute. IFD were observed in 16 courses and the incidence was 2.3 %. A multivariate analysis showed that the factors associated with IFD were primary refractoriness (adjusted odds ratio (aOR), 4.22; 95 % confidence interval (CI), 1.38–13.0; p value?=?0.012), two (aOR, 10.5, 95 % CI, 1.20–91.7; p?=?0.033) or more (aOR, 26.2; 95 % CI, 3.27–210; p?=?0.002) previous treatment lines, and the minimum neutrophil count during the therapies equal to or less than 500/μL (aOR, 9.69; 95 % CI, 1.25–74.9; p?=?0.030). Using these factors, we created the IFD scoring model by assigning one point to each of primary refractoriness, two previous treatment lines and treatment that caused neutropenia (≤500/μL minimal neutrophil count) and two points to three or more previous treatment lines. The IFD incidence of lower risk group (IFD score <3) was 0.19 % and that of higher (IFD score ≥3) was 9.0 %. In conclusion, adequate prophylaxis for IFD might be required for patients with primary refractoriness, repeated therapies, or therapies which cause neutropenia. Furthermore, the IFD scoring model of this study underscores the need to account for disease and host factors in determining administration of adequate prophylaxis in salvage treatments for malignant lymphoma.     

Association between primary Sjögren’s syndrome and pregnancy complications: a systematic review and meta-analysis

Systemic autoimmune disorders may interfere with normal reproductive function resulting in negative outcome of pregnancy. Primary Sjögren’s syndrome (pSS) is a common rheumatic disease that mostly affects females. There are many reports that this condition may increase risk of pregnancy complications and fetal loss. However, data regarding these adverse outcomes are scarce and inconclusive. We performed a systematic review and meta-analysis of available articles that assess the association between pSS and adverse pregnancy outcome. We comprehensively searched the databases of MEDLINE and EMBASE from their dates of inception to March 2016 and reviewed papers with validity criteria. A random-effects model was used to evaluate pregnancy complications in patients with pSS and healthy controls. From 20 full-text articles, 7 studies involving 544 patients and 1586 pregnancies were included in the meta-analysis. Fetal complications included spontaneous abortion, stillbirth, neonatal deaths, and intrauterine growth retardation. Compared with healthy pregnancy, patients with pSS had significantly higher chance of neonatal deaths (pooled odds ratio (OR)?=?1.77, 95 % confidence interval (CI) 1.28 to 1.46, p?=?0.01). However, there were no significant associations between pSS and premature birth (OR?=?2.10, 95 % CI 0.59–7.46, p?=?0.25), spontaneous abortion (OR?=?1.46, 95 % CI 0.72–2.93, p?=?0.29), artificial abortion (OR?=?1.12, 95 % CI 0.52–2.61, p?=?0.71), or stillbirth (OR?=?1.05, 95 % CI 0.38–2.97, p?=?0.92). There is an increased risk of fetal loss in pregnant patients with pSS. The presented evidence further supports multidisciplinary care for these patients to prevent complications during pregnancy.     

Infliximab versus cyclosporine as rescue therapy in acute severe steroid-refractory ulcerative colitis: a systematic review and meta-analysis

Purpose

Acute severe colitis affects 25 % of patients with ulcerative colitis (UC). Up to 30–40 % of these patients are resistant to intensive steroid therapy and therefore require rescue therapy to prevent emergent colectomy. Data comparing rescue therapy using infliximab and cyclosporine are limited and equivocal. This study evaluates the outcomes of UC patients receiving infliximab or cyclosporine as rescue therapy in acute severe steroid-refractory exacerbations.

Methods

Electronic databases (PubMed, EMBASE, and Cochrane database) were searched for studies directly comparing infliximab and cyclosporine in UC, and references of included studies were screened. Two independent reviewers identified relevant studies and extracted data. Meta-analyses were performed using the random effect model. Outcome measures included 3- and 12-month colectomy rates, adverse drug reactions, and postoperative complications.

Results

Six retrospective cohort studies describing 321 patients met the inclusion criteria. The meta-analysis did not show significant differences between infliximab and cyclosporine in the 3-month colectomy rate (odds ratio (OR)?=?0.86, 95 % confidence interval (CI)?=?0.31–2.41, p?=?0.775), in the 12-month colectomy rate (OR?=?0.60, 95 % CI?=?0.19–1.89, p?=?0.381), in adverse drug reactions (OR?=?0.76, 95 % CI?=?0.34–1.70, p?=?0.508), and in postoperative complications (OR?=?1.66, 95 % CI?=?0.26–10.50, p?=?0.591). Funnel plot revealed no publication bias.

Conclusions

Infliximab and cyclosporine are comparable when used as rescue therapy in acute severe steroid-refractory UC. Randomized trials are required to further evaluate these agents.

     

Polymorphisms of the IL-23R gene are associated with primary immune thrombocytopenia but not with the clinical outcome of pulsed high-dose dexamethasone therapy

Primary immune thrombocytopenia (ITP) is an autoimmune heterogeneous disorder that is characterized by decreased platelet count. The interleukin-23 receptor (IL-23R) has been identified as a susceptibility gene for the development of multiple autoimmune diseases. To investigate the possible association of IL-23R gene single-nucleotide polymorphisms (SNPs) with ITP and the association with the clinical outcome of pulsed high-dose dexamethasone (HD-DXM) therapy, four SNPs in the IL-23R gene, rs10889677, rs1884444, rs7517847, and rs11209032, were tested in a cohort of 75 ITP subjects and 81 controls by direct sequencing. IL-23R rs1884444 GT/TT variant genotypes were observed to be associated with significantly increased risk of ITP as compared with controls (GT/TT vs. GG: odds ratio (OR) 2.776, 95 % confidence intervals (CI) 1.086–7.090, p?=?0.028). However, other three SNPs revealed no statistically significant differences between patients and controls (rs10889677 CA/AA vs. CC: OR 2.200, 95 % CI 0.727–6.661, p?=?0.155; rs11209032 GA/AA vs. GG: OR 0.747, 95 % CI 0.379–1.472, p?=?0.399; rs7517847 TG/GG vs. TT: OR 1.031, 95 % CI 0.544–1.956, p?=?0.925). Furthermore, IL-23R SNPs revealed no association with clinical outcome of HD-DXM therapy. This study suggests that polymorphism in the IL-23R gene, rs1884444, indicates a significant association with susceptibility to ITP in a recessive genetic model but does not have association with the clinical outcome of HD-DXM therapy.     

Osteopontin circulating levels correlate with renal involvement in systemic lupus erythematosus and are lower in ACE inhibitor-treated patients

Elevated serum levels of osteopontin have been associated with cardiovascular disease, diabetic nephropathy, and autoimmune disease activity. Aim of the study was to investigate the relationship between osteopontin serum levels and renal damage in a population of patients with systemic lupus erythematosus (SLE). Osteopontin serum levels were analyzed in 101 SLE patients and compared to those of 115 healthy controls. Associations between osteopontin levels and renal involvement, disease activity and damage index, biochemical parameters, and therapy were assessed. Overall osteopontin serum levels were higher in SLE patients (median, 17.93 ng/mL; interquartile range, 8.13–35.07 ng/mL) than in healthy controls (median, 5.62 ng/mL; interquartile range, 2.61–13.83 ng/mL). Univariate logistic analysis among cases showed that high osteopontin levels (higher vs medium–lower tertile) were associated with renal involvement (p?=?0.012), renal function (p?=?0.007), proteinuria (p?=?0.011), anemia (p?p?p?=?0.008), proteinuria (OR?=?4.56; 95 % CI, 1.15–18.04; p?=?0.027), anemia (OR?=?4.66; 95 % CI, 1.25–17.43; p?=?0.008), and use of renin–angiontensin system antagonists (OR?=?0.234; 95 % CI, 0.06–0.98; p?=?0.047). This study shows that elevated osteopontin serum levels significantly correlate with renal involvement and anemia in SLE. Moreover, it suggests that renin–angiontensin system antagonists decrease osteopontin levels—this effect is consistent with the inhibitory effect of these drugs on osteopontin renal expression, detected in animal models by other authors, and may provide a new rationale for their employment.     

Risk factors for severe bacterial infections in patients with systemic autoimmune diseases receiving rituximab

The risk of serious bacterial infectious events (SIEs) after an RTX course used in severe and refractory cases of systemic autoimmune diseases (SAID) is well known. Risk factors for SIEs merit investigation. For this case–control study, data were collected in a single centre of internal medicine and included all patients who received rituximab (RTX) for SAID between 2005 and 2011 (rheumatoid arthritis was excluded). Sixty-nine patients with SAID received a total of 87 RTX courses. Thirteen SIEs were reported in 12 patients leading to death in 5 patients. Patients with a history of SIE were significantly older (63.6?±?18.8 vs 48.8?±?16.7; p?=?0.0091), suffered most frequently of diabetes mellitus (33.3 % vs 5.3 %, p?=?0.015), had a lower CD19 count (1.0?±?1.2/mm³ vs 3.9?±?7.2/mm³) and had most frequently a prednisone dose >15 mg/day (91.7 % vs 47.7 %) at the start of the first RTX course. The SIE rate was 18.7 per 100 patient-years. At the initiation of the RTX course, risk factors for SIEs were lower IgG levels (OR?=?0.87, 95%CI?=?0.77–0.99, p?=?0.03), lower CD19 count (OR?=?0.85, 95%CI?=?0.73–1.00) and creatinine clearance?≤?45 ml/min (OR?=?7.78, 95%CI?=?1.36–44.38, p?=?0.002). Conversely history of pneumococcal vaccination significantly decreased the risk of SIEs (OR?=?0.11, 95%CI?=?0.03–0.41, p?=?0.0009). Concomitant treatment with prednisone at a dose >15 mg/day significantly increased the SIE risk (OR?=?8.07, 95%CI?=?1.94–33.59, p?=?0.0004). SIEs are frequent in SAID treated with RTX, particularly in patients receiving high-dose corticosteroids, in patients with renal insufficiency and in patients with low IgG levels or a low CD19 count.     

Prognostic impact of beta-2 microglobulin in patients with extranodal natural killer/T cell lymphoma

Although serum beta-2 microglobulin (B2M) has been suggested as an independent prognostic factor for several lymphoproliferative diseases, it has rarely been investigated in extranodal natural killer/T cell lymphoma (ENKTL). From a prospectively collected database, 145 patients with ENKTL were identified. Among them, a total of 101 patients were included in the analysis, with exclusion of patients without baseline serum B2M level and those did not receive anticancer therapy. Serum B2M (<3.0 vs. ≥3.0 mg/L) was analyzed for association with overall survival (OS). Seventy-nine (78 %) patients had nasal ENKTL, and 22 (22 %) had extranasal ENKTL. In overall patients, median OS was 26.7 months (95 % confidence interval (CI), not assessable), with a median follow-up of 32.4 months (range, 0.9–155.2 months). While median OS was not reached in patients with nasal ENKTL, extranasal ENKTL group had median OS of 5.1 months (95 % CI, 1.2–8.9 months; p?<?0.001). Baseline serum B2M was significantly associated with OS in patients with nasal ENKTL (p?<?0.001). This was consistent in limited (stages I and II) nasal ENKTL (p?=?0.002) and disseminated (stages III and IV) nasal ENKTL (p?=?0.02). However, there was no difference of OS in extranasal ENKTL patients (p?=?0.69). In multivariate analysis including other prognostic factors, elevated serum B2M was significantly associated with poor OS (hazard ratio (HR)?=?3.8, 95 % CI 1.7–8.2, p?=?0.001, in a model including Korean Prognostic Index, and HR?=?3.6, 95 % CI 1.6–8.2, p?=?0.002, in a model including International Prognostic Index). In patients with nasal ENKTL, baseline serum B2M is a powerful prognostic factor. The prognostic value of B2M was independent of previously established prognostic models. Further investigations are necessary to validate the role of B2M in ENKTL.     

GSTT1 and GSTM1 polymorphisms predict treatment outcome for acute myeloid leukemia: a systematic review and meta-analysis

Glutathione S-transferases (GSTs) contribute to the metabolism of different xenobiotics and anticancer drugs and confer protection against oxidative stress thus may influence the treatment outcome of acute myeloid leukemia (AML). Studies regarding the association between GSTT1 and GSTM1 polymorphisms and treatment outcome in AML patients showed an inconsistent result. A systematic review and meta-analysis were performed to further explore this association. PubMed, Hartford User Group Exchange (HUGE), and China National Knowledge Infrastructure (CNKI) databases were searched for all related publications. Statistical analyses were analyzed by using RevMan 5.0 and Stata 9.0 softwares. A total of 1,837 patients in 11 studies were included. GSTT1 null genotype was found to be significantly associated with a reduced response after first course of induction chemotherapy (odds ratio (OR)?=?0.894, 95 % confidence interval (CI)?=?0.818–0.977, P?=?0.013), progression-free survival (PFS; hazard ratio (HR) = 0.698, 95 % CI?=?0.520–0.937, P?=?0.017), and overall survival (OS; HR?=?0.756, 95 % CI?=?0.618–0.925, P?=?0.007) in Asian population. GSTM1/GSTT1 double-null genotype was also identified to be significantly associated with response after the first course of induction chemotherapy (OR?=?0.40, 95 % CI?=?0.24–0.67, P?=?0.0003). Our study suggested that GSTT1 null genotype and GSTT1/GSTM1 double-null genotype were associated with a worse treatment outcome for AML patients, especially in Asian population.     

Cross-cultural adaptation and validation of the Spanish version of the Cumberland Ankle Instability Tool (CAIT): an instrument to assess unilateral chronic ankle instability

The Cumberland Ankle Instability Tool (CAIT) is a valid instrument to determine the presence of chronic ankle instability (CAI) and to assess its severity. Self-report test is very useful for researchers and clinical practice, and CAI is a widespread tool. Nevertheless, there is lack of measurement instruments validated into Spanish, which represents a major difficulty for research dealing with a Spanish-speaking population. The questionnaire was cross-culturally adapted into Spanish. The psychometric properties tested in the Spanish version of the CAIT were measured for internal consistency, test–retest reliability, construct validity, criterion validity, and responsiveness in 108 participants who were recruited from several fitness centers. The Spanish version of the CAIT had high internal consistency (Cronbach's α?=?0.766) and reliability (intraclass correlation coefficient?=?0.979, 95 % confidence interval (CI)?=?0.958–0.990). Correlation with the 36-item Short-Form Health Survey (SF-36) physical component summary score (rho?=?0.241, p?=?0.012) was greater than the SF-36 mental component summary score (rho?=??0.162, p?=?0.094). The construct validity shows three different factors in the questionnaire and good responsiveness with a mean change of ?2.43 (95 % CI?=??3.12 to 1.73, p?<?0.0001) and a size effect of Cohen's d?=?1.07. The Spanish version of the CAIT has been shown to be a valid and reliable instrument for measuring chronic ankle instability and constitutes a useful instrument for the measurement of CAI in the clinical setting in Spain.     

Association analysis of genetic variants in microRNA networks and gastric cancer risk in a Chinese Han population

Purpose

To investigate associations between genetic variants involved in microRNA networks (microRNA biogenesis, microRNA and microRNA binding sites) and risk of gastric cancer.

Methods

We genotyped 19 SNPs of the microRNA-related genes in a case–control study of 311 gastric cancers and 425 cancer-free controls in a Chinese Han population.

Results

We found that two of the SNPs were significantly associated with gastric cancer. Inhibitory effect of minor allele T of rs2071504 SNP within the exon of POLR2A gene was significantly associated with gastric carcinogenesis (p?=?0.033, aOR?=?0.742, 95%CI?=?0.564–0.977) and the SNP rs895819 in the miR-27a gene with the minor allele C presented significantly reduced risk to gastric cancer (p?=?0.037, aOR?=?0.771, 95%CI?=?0.604–0.985). Further stratified analysis with regard to clinical pathological parameters of the patients indicated that the SNP rs2071504 was associated with lymph node metastasis (p?=?0.021, aOR?=?0.529, 95%CI?=?0.307–0.910) and TMN stage (p?=?0.021, aOR?=?0.532, 95%CI?=?0.311–0.908), respectively.

Conclusions

Our findings provided evidence that the SNP rs2071504 in the exon of POLR2A gene would not only confer a decreased risk of gastric cancer, but also influence lymph node metastasis and TMN stage of gastric cancer in the Chinese population.     

Preoperative adipocytokines as a predictor of surgical infection after colorectal surgery: a prospective survey

Background

Infections are the leading cause of morbidity and mortality after colorectal surgery. Obesity is a well-known risk factor for wound infection, but it does not seem to increase the risk of other infectious complications. The aim of this study was to look for a relationship between the fatty tissue metabolism measured by adipocytokine levels and the risk of postoperative infection.

Patients and methods

Preoperative plasma levels of eight adipocytokines, cholesterol, triglycerides, insulin and C-reactive protein (CRP) were measured in consecutive patients undergoing elective colorectal surgery between June 2008 and June 2011. Information about epidemiological and clinical characteristics was obtained for each patient. All infections in the 30 days following surgery were recorded.

Results

Among the 174 patients included, 49 (28 %) presented with a postoperative infection: 41 surgical site infections and 8 other infections. Preoperative leptin, insulin and CRP were significantly higher in patients with postoperative infection (p?=?0.025, p?=?0.020 and p?=?0.044, respectively), but only leptin was predictive of infection in multivariate analysis (odds ratio (OR)?=?1.89, 95 % confidence interval (CI) 1.18–3.03, p?=?0.008). The predictive value of leptin was slightly lower for surgical site infection (OR?=?1.65, 95 % CI 1.06–2.55, p?=?0.025). Leptin levels were independent of the other adipocytokine levels but not of the body mass index.

Conclusion

Although markers of inflammation and insulin resistance are also related to the onset of surgical infection, leptin correlates more closely with the risk of infection than does any other factor. However, its effect could be partially mediated by the body mass index.     

Combination of fludarabine, amsacrine, and cytarabine followed by reduced-intensity conditioning and allogeneic hematopoietic stem cell transplantation in patients with high-risk acute myeloid leukemia

Sequential use of chemotherapy and reduced-intensity conditioning (RIC) with allogeneic stem cell transplantation (SCT) has been proposed to improve the treatment outcomes in patients with high-risk acute myeloid leukemia (AML). Here, we present our experience with this procedure in a cohort of 60 AML patients with primary induction failure (n?=?9); early, refractory, or ≥ second relapse (n?=?41); or unfavorable cytogenetics (n?=?10). A combination of fludarabine (30 mg/m²/day), cytarabine (2 g/m²/day), and amsacrine (100 mg/m²/day) for 4 days was used. After 3 days of rest, RIC was carried out, consisting of 4 Gy total body irradiation, antithymocyte globulin (ATG-Fresenius), and cyclophosphamide (fludarabine, amsacrine, and cytarabine (FLAMSA)-RIC protocol). Prophylactic donor lymphocyte infusions (pDLIs) were given in patients with complete remission (CR) and without evidence of graft-versus-host disease ≥120 days after SCT. The median time of neutrophil engraftment was 17 days. CR was achieved in 47 of 60 patients (78 %). Eleven patients received pDLIs resulting in long-term CR in eight of them. Non-relapse mortality after 1 and 3 years was 25 and 28 %, respectively. With a median follow-up of 37 months (range, 10–69), 3-year overall survival and 3-year progression-free survival were 42 and 33 %, respectively. In a multivariate analysis, dose of CD34(+) cells >5?×?10⁶/kg (p?=?0.005; hazard ratio (HR)?=?0.276), remission of AML before SCT (p?=?0.044; HR?=?0.421), and achievement of complete chimerism after SCT (p?=?0.001; HR?=?0.205) were significant factors of better overall survival. The use of the FLAMSA-RIC protocol in suitable high-risk AML patients results in a long-term survival rate of over 40 %.     

Progression of carotid atherosclerosis in patients with systemic lupus erythematosus

The progression of carotid atherosclerosis in lupus patients is frequently encountered, and it is determined by both traditional and nontraditional risk factors. Of the 181 patients initially included in the study, 157 patients were reevaluated after 39(37–42)?months. The progression of atherosclerosis was defined as the increase in the intima-media thickness (IMT) >0.15 mm and/or an increase of the plaque score. The predictive factors of progression were identified using the Poisson regression model. The median of the cohort age at baseline was 38 years (range 29–46 years; 96.2% female, 75.8% nonwhite). Carotid atherosclerosis progression was observed in 43 patients (27.4%), an increased plaque score was observed in nine patients (5.7%), an increase of IMT >0.15 mm was observed in 31 (19.7%), and both issues were present in three patients (1.9%). The univariate determinants of atherosclerosis progression were age, systemic lupus erythematosus (SLE) duration, and higher serum level of triglycerides (p?<?0.05). The presence of nephrotic proteinuria (p?=?0.063), stage 3 or greater chronic kidney disease (p?=?0.091), and longer duration of prednisone use (p?=?0.056) showed a tendency towards association with progression of atherosclerosis. The independent risk factors for progression were the SLE duration (p?=?0.008, RR?=?1.06, 95% CI?=?1.03–1.10) and the presence of nephrotic proteinuria (p?=?0.022, RR?=?4.22, 95% CI?=?2.18–8.15). The progression of atherosclerosis occurred in a substantial number of young SLE patients during a short-term follow-up. The independent factors associated with this progression emphasize the importance of SLE in determining atherosclerosis in these individuals.     

Prevalence of irritable bowel syndrome and functional dyspepsia,overlapping symptoms,and associated factors in a general population of Bangladesh

Background

This community-based survey aimed to find out the prevalence of irritable bowel syndrome (IBS), functional dyspepsia (FD), overlapping symptoms, and associated factors for overlap.

Method

By cluster sampling method, 3,000 (1,523 male) randomly selected adult subjects in the Sylhet district of Bangladesh were interviewed by a questionnaire based on ROME III criteria. Multivariate logistic regression analyses were done to find out the factors for overlap with significance level set at ≤0.05.

Results

The mean age of the study population was 33.9?±?16.4 years. Prevalence of IBS and FD and IBS-FD were 12.9 % (n?=?387), 8.3 % (n?=?249), and 3.5 % (n?=?105), respectively. Approximately 27.1 % of IBS patients and 42.1 % of FD patients had overlapping IBS-FD. The odds ratio for IBS-FD overlap was 6.3 (95 % CI, 4.8–8.4). Mean age (p?=?0.011) and epigastric pain (p?=?0.002) were more in overlap patients than FD alone, whereas epigastric pain syndrome subtype (p?<?0.009) was more prevalent in lone FD subjects. In the multivariate logistic analysis, early satiety (OR, 3.0; 95 % CI, 1.2–7.5; p?=?0.018) and epigastric pain (OR, 14.5; 95 % CI, 5.0–42.1; p?=?0.000) in FD patients appeared as independent risk factors for overlap. Bloating (p?=?0.026), <3 stools per week (p?=?0.050), abdominal pain reduced by defecation (p?=?0.002), abdominal pain severity score (p?=?0.004), and overall symptom frequency score (p?=?0.000) were more in overlap patients than IBS-alone patients. In IBS patients, bloating (OR, 3.6; CI, 2.0–6.5; p?=?0.000) was found as potential symptom associated with IBS-FD overlap.

Conclusion

FD was a less prevalent disorder than IBS in our community, and significant overlap existed between the two disorders. Early satiety, epigastric pain, and bloating were important factors associated with overlap.     

Serial Echocardiographic Characteristics,Novel Biomarkers and Cachexia Development in Patients with Stable Chronic Heart Failure

Little is known regarding objective predictors of cachexia affecting patients with heart failure (HF). We studied 108 stable chronic systolic HF patients with serial echocardiography and biomarker measurements over 10 months. Cachexia was defined as weight loss ≥5 % from baseline or final BMI <20 kg/m²; 18.5 % developed cachexia. While there were no significant differences in baseline or serial echocardiographic measures in those developing cachexia, we found significant differences in baseline amino-terminal pro-B type natriuretic peptide (NT-proBNP), highly sensitive troponin I, sST2, and endothelin-1. Baseline log NT-proBNP (hazard ratio (HR)?=?2.57, p?=?0.004) and edema (HR?=?3.36, p?=?0.04) were predictive of cachexia in an adjusted analysis. When serial measurement of biomarkers was considered, only percent time with NT-proBNP ≥1000 pg/mL was predictive of cachexia. Thus, a close association exists between baseline and serial measurement of NT-proBNP and HF cachexia.     

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.     

Risk factors associated with early- versus late-onset implantable cardioverter-defibrillator infections

Aims

The infection rates of implantable cardioverter-defibrillators systems (ICDs) are higher than that of permanent pacemaker. Risk factors associated with ICD infection have not been characterized and are the subject of the current investigation.

Methods

All patients who had an ICD implanted at Mayo Clinic Rochester between 1991 and 2008 were retrospectively reviewed. Each case of ICD infection was matched with two non-infected controls. Cases of ICD infection were further stratified by early- (??6 months) versus late-onset (>6 months) infection. Multivariable analysis was performed to identify significant risk factors for ICD infection.

Results

Sixty-eight patients with ICD infection and 136 matched controls met the inclusion criteria. Thirty-five cases presented with early-onset infection and 33 had late-onset device infection. Staphylococcal species were the most common pathogens in both groups of patients. Patients with early-onset infection were more likely to present with generator pocket infection (p?=?0.02). Patients with multiple comorbid conditions (high Charlson index) tended to have longer hospital stay during implantation admission (p?=?0.009). In a multivariable logistic regression model, the presence of epicardial leads (odds ratio (OR)?=?9.7, p?=?0.03) and postoperative complications at the generator pocket (OR?=?27.2, p?<?0.001) were significant risk factors for early-onset ICD infection, whereas longer duration of hospitalization at the time of implantation (2 days versus 1 day: OR?=?33.1, p?<?0.001; ??3 days versus 1 day: OR?=?49.0, p?<?0.001) and chronic obstructive pulmonary disease (OR?=?9.8, p?=?0.02) were associated with late-onset infections.

Conclusions

Our study findings suggest that risk factors associated with early- and late-onset ICD infection are different. While circumstances that may increase the chances of pocket contamination in the perioperative period are more likely to be associated with early-onset ICD infection, overall poor health of the host may increase the likelihood of late-onset ICD infection. These factors should be considered when developing strategies to minimize risk of device infection.     

The prevalence and correlates of habitual snoring during pregnancy

Purpose

Mounting evidence implicate habitual snoring, a prominent symptom of sleep-disordered breathing, as an important risk factor for adverse pregnancy outcomes including preeclampsia and gestational diabetes. Little, however, is known about the determinants of habitual snoring among pregnant women. We sought to assess its prevalence and to identify maternal characteristics associated with habitual snoring during pregnancy.

Methods

Pregnant women (N?=?1,303) receiving prenatal care provided information about habitual snoring before and during pregnancy in in-person interviews completed in early pregnancy. We calculated adjusted odds ratios (aOR) and 95 % confidence intervals (95 % CI) from multivariable models designed to identify factors associated with snoring during pregnancy.

Results

Approximately 7.3 % of pregnant women reported habitual snoring during early pregnancy. The odds of habitual snoring during pregnancy was strongly related with maternal reports of habitual snoring prior to the index pregnancy (aOR?=?24.32; 95 % CI, 14.30–41.51). Advanced maternal age (≥35 years) (aOR?=?2.02; 95 % CI, 1.11–3.68), history of pregestational diabetes (aOR?=?3.61; 95 % CI, 1.07–12.2), history of mood and anxiety disorders (aOR?=?1.81; 95 % CI, 1.02–3.20), and prepregnancy overweight (25–29.9 kg/m²) (aOR?=?2.31; 95 % CI, 1.41–3.77) and obesity (≥30 kg/m²) (aOR?=?2.81; 95 % CI, 1.44–5.48) status were statistically significant risk factors for habitual snoring during pregnancy. In addition, maternal smoking during pregnancy (aOR?=?2.70; 95 % CI, 1.17–6.26) was associated with habitual snoring during pregnancy.

Conclusions

Identification of risk factors for habitual snoring during pregnancy has important implications for developing strategies aimed at reducing the prevalence of sleep-disordered breathing, promoting improved sleep hygiene and improved pregnancy outcomes among reproductive-age women.     

Angiotensin-converting enzyme gene polymorphism in north Indian population with obstructive sleep apnea

Background

A deletion of 287-bp Alu repeat of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene is associated with hypertension.

Purpose

The aim of this study is to determine the frequency of ACE (I/D) polymorphism in patients with obstructive sleep apnea (OSA).

Methods

Genotyping of ACE (I/D) gene polymorphism and estimation of serum angiotensin-converting enzyme (SACE) activity were done in 813 subjects who underwent polysomnography. Of these, 395 were apneics and 418 were non-apneics.

Results

The frequencies of II genotype (OR = 1.8, 95 % CI 1.26–2.60, p?=?0.001) and I allele (OR = 1.4, 95 % CI 1.13–1.69, p?=?0.001) of ACE gene were found to be significantly increased in patients with OSA as compared to patients without OSA. Frequency of II genotype was significantly decreased (OR = 0.46, 95 % CI 0.28–0.77, p?=?0.003) in OSA patients with hypertension. In contrast, the frequencies of ID (OR?=?1.80, 95 % CI 1.08–2.99, p?=?0.024) and DD genotypes (OR?=?2.15, 95 % CI 1.30–3.57, p?=?0.003) were significantly increased in this group. The activity of SACE was significantly decreased in the apneic group as compared to the non-apneic group (OR?=?0.99, 95 % CI 0.98–1.00, p?=?0.04).

Conclusions

The findings suggest that II genotype confers susceptibility towards development of OSA whereas DD genotype confers susceptibility towards hypertension irrespective of OSA.