Combined phenotype of 4 markers improves prognostic value of patients with colon cancer

IntroductionCombination of multiple biomarkers representing distinct aspects of tumor biology will have a better prognostic value. This study was to identify prognostic subgroups of colon adenocarcinoma by combined analysis of synuclein-gamma (SNCG), a human homologue of piwi (Hiwi), phosphatase of regenerating liver-3 (PRL-3), arrest-defective protein 1, homolog A (ARD1) and clinicopathologic features in 225 colon adenocarcinoma specimens.MethodsImmunohistochemistry for 4 tumor markers was performed in whole tissue sections from 225 colon adenocarcinoma patients with complete clinicopathologic data and up to 10-year follow-up. The immunohistochemical expression patterns were examined individually and in multimarker combinations. Univariate and multivariate analyses were performed to identify independent predictive markers of poor outcome.ResultsWith the tumor marker positive rate [32.0% (62/225) for SNCG; 76.9% (173/225) for combined SNCG/Hiwi/PRL-3/ARD1] and the detecting accuracy [61.9% (252/407) for SNCG; 82.6% (336/407) for combined SNCG/Hiwi/PRL-3/ARD1] increasing, incremental value of combined SNCG/Hiwi/PRL-3/ARD1 (P < 0.001; hazard ratios (HR), 3.2) to poor outcome was found. Stratified by lymph node, Hiwi alone (P = 0.004; HR, 3.2) led to poor outcome in patients without lymph node metastasis (LN—), and SNCG (P < 0.001; HR, 2.5) had independently poor prognostic value for patients with lymph node metastasis (LN +).ConclusionsMultimarker phenotypes improved tumor positive rate, detecting accuracy and prognostic value. In addition, a subgroup of more aggressive tumors can be identified by evaluating Hiwi level in LN— cancer, and SNCG level in LN + cancer.     

Decreased expression of HOXB9 is related to poor overall survival in patients with gastric carcinoma

BackgroundStudies have demonstrated the implication of HOXB9 in tumorigenesis, but its role in gastric carcinoma remains unknown.AimsTo investigate the expression and prognostic value of HOXB9 in patients with gastric carcinoma.MethodsThe localization and expression of HOXB9 in gastric cancer cells lines were detected by immunofluorescence and western blot. The mRNA and protein expression level of HOXB9 was detected in subjects with gastric carcinoma and paired non-cancerous tissues. Correlation between HOXB9 expression and clinicopathological parameters, the association of HOXB9 expression with the patients’ survival rate was also assessed.ResultsHOXB9 was predominantly localized in the cell nucleus. A significant decrease in HOXB9 intensity in poorly differentiated gastric cancer cells is evident (P < 0.01). A lower mRNA and protein expression level of HOXB9 was detected in gastric carcinoma (P < 0.01). Decreased expression of HOXB9, poorly differentiation status and the presence of lymph node metastasis predict shorter overall survival (P < 0.05). Patients without HOXB9 expression had a lower overall survival rate (P < 0.01). Multivariate Cox regression analysis showed HOXB9 was an independent prognostic factor in gastric carcinoma (P < 0.01).ConclusionsHOXB9 is down-regulation in gastric carcinoma and may be a novel prognostic marker for poorer clinical outcome for patients with gastric carcinoma.     

A meta-analysis of efficacy of topical steroids in eosinophilic esophagitis: From the perspective of histologic,clinical, and endoscopic outcome

BackgroundSwallowed topical steroids are a mainstay drug therapy for eosinophilic esophagitis (EoE), studies have demonstrated good histologic response, but with enormous discrepancy in clinical and endoscopic improvement. We conducted this meta-analysis to investigate the efficacy of topical steroids in EoE in histological, clinical and endoscopic improvement.MethodsSeveral databases were searched from inception to August 1, 2019 for randomized controlled trials (RCTs) comparing topical steroids with placebo for EoE in the short-term. The outcomes of interest mainly included basic characteristics of the studies, histologic, clinical, endoscopic response rate and adverse events. The results were pooled together using Reviewer Manager 5.3.5 software, and inconsistency was quantified using I² statistics.ResultsNine studies were eventually selected. The results showed that topical steroids were effective in inducing histologic response compared with placebo for both complete (OR 35.82, 95% CI 14.98–85.64, P < 0.0001; I² = 0, P = 0.72) and partial response (OR 28.44, 95% CI 8.56–94.47, P < 0.0001; I² = 70%, P = 0.0009). Moreover, topical steroids were useful in gaining clinical response (OR 2.53, 95% CI 1.14–5.60, P = 0.02; I² = 60%, P = 0.02) and endoscopic response (OR 3.51, 95% CI 1.47–8.36, P = 0.005; I² = 0, P = 0.57). Generally, topical steroids are well tolerated. The most common adverse events are infections and infestations (59 cases).ConclusionTopical steroids were effective in inducing histological, clinical and endoscopic response in the short-term, and the adverse events were almost tolerable; however, we should interpret the result of clinical and endoscopic response with caution.     

The value of plasma osteopontin levels as a predictive factor of disease stage and recurrence in patients with bladder urothelial carcinoma: A prospective study

This study was performed in order to determine the value of plasma osteopontin (OPN) levels as a predictive factor of disease stage and recurrence in patients with bladder urothelial carcinoma (UC). Data from 50 patients diagnosed to have bladder UC after transurethral resection of bladder tumor (TURBT) from 2009 to 2010 were evaluated prospectively. Blood tests were performed before and after TURBT, and plasma OPN levels were measured using enzyme-linked immunosorbent assay. Differences in OPN levels according to clinicopathologic variables were analyzed statistically. Significant differences in plasma OPN levels were observed between groups with and without muscle invasion (89.16 vs. 67.08 ng/mL, p = 0.041). Comparison according to tumor grade found no significant difference between high and low grade groups (p = 0.115). Mean plasma OPN levels decreased after TURBT without statistical significance (p = 0.571). Between groups with recurrence and those without recurrence, OPN levels of the group with recurrence were higher without statistical significance (p = 0.161). Comparison of plasma OPN levels according to performance of radical cystectomy (RC) showed significant differences; patients who underwent RC showed higher levels of plasma OPN (95.58 vs. 70.37 ng/mL, p = 0.030). Comparison according to T stage after RC showed significant differences in OPN levels (T1: 67.45, T2: 86.60 and T3: 95.23 ng/mL, respectively, p = 0.006). The group with lymph node invasion showed significantly higher levels of OPN, compared to the group without invasion (153.24 vs. 68.03 ng/mL, p = 0.017). Preoperative plasma OPN levels correlated to muscle invasion of bladder UC and pathological stage after RC.     

Un nouvel index pour évaluer le vieillissement artériel indépendamment de la pression artérielle : pOpscore®

AimPulse wave velocity does not correlate to age in the upper limb but in the aorta and lower limb. We studied the link between ageing and pulse wave transit time (PWtt) indexes at the toe and finger.Patients and methodsMeasurements were performed in 300 patients in occupational medicine and primary care after 5 minutes supine rest using the device studied (pOpmètre^®, Axelife SAS, France). It measures transit time between R-ECG and finger or toe pulse signal (ttf or ttt respectively). We define as follows three indexes: difference between transit times: Dtf = ttt ? ttf; pulse wave velocity PWVft = k*subjects height/Dtf (m/s); and the pOpscore^® as the ratio of toe PWV/fingerPWV.ResultsOf the 300 tested patients, 147 were analysed using univariate correlation: age (P < 10^?4), SBP (P < 10^?4), DBP (P < 0.02) and BMI (P < 0.04) correlated to Dtf, PWVtf and pOpscore^®. Using stepwise regression analysis with Age, BMI, SBP, DBP, MBP: Dtf was dependent with age (P < 10^?4) and SBP (P < 0.01); PWVtf with age (P < 0.0001), SBP (P < 0.01) and DBP (P < 0.05); pOpscore^® was dependent only to age (P < 10^?4).ConclusionIn this study, in contrast with the other vascular indexes studied dependent to age and blood pressure, pOpscore^® was dependent only to ageing. pOpmètre^® is a promising technique for routine determination of arterial stiffness and pOpscore^® appears to be appropriate to study the structural vascular ageing in outpatient.     

Associations between a fetal imprinted gene allele score and late pregnancy maternal glucose concentrations

AimWe hypothesised that some of the genetic risk for gestational diabetes (GDM) is due to the fetal genome affecting maternal glucose concentrations. Previously, we found associations between fetal IGF2 gene variants and maternal glucose concentrations in late pregnancy.MethodsIn the present study, we tested associations between SNP alleles from 15 fetal imprinted genes and maternal glucose concentrations in late pregnancy in the Cambridge Baby Growth and Wellbeing cohorts (1160 DNA trios).ResultsFour fetal SNP alleles with the strongest univariate associations: paternally-transmitted IGF2 rs10770125 (P-value = 2 × 10^–4) and INS rs2585 (P-value = 7 × 10^–4), and maternally-transmitted KCNQ1(OT1) rs231841 (P-value = 1 × 10^–3) and KCNQ1(OT1) rs7929804 (P-value = 4 × 10^–3), were used to construct a composite fetal imprinted gene allele score which was associated with maternal glucose concentrations (P-value = 4.3 × 10^–6, n = 981, r² = 2.0%) and GDM prevalence (odds ratio per allele 1.44 (1.15, 1.80), P-value = 1 × 10^–3, n = 89 cases and 899 controls). Meta-analysis of the associations including data from 1367 Hyperglycaemia and Adverse Pregnancy Outcome Study participants confirmed the paternally-transmitted fetal IGF2/INS SNP associations (rs10770125, P-value = 3.2 × 10^–8, rs2585, P-value = 3.6 × 10^–5) and the composite fetal imprinted gene allele score association (P-value = 1.3 × 10^–8), but not the maternally-transmitted fetal KCNQ1(OT1) associations (rs231841, P-value = 0.4; rs7929804, P-value = 0.2).ConclusionThis study suggests that polymorphic variation in fetal imprinted genes, particularly in the IGF2/INS region, contribute a small but significant part to the risk of raised late pregnancy maternal glucose concentrations.     

Altered molecular signature of intestinal microbiota in irritable bowel syndrome patients compared with healthy controls: A systematic review and meta-analysis

BackgroundMany studies have reported significant changes in intestinal microbiota in irritable bowel syndrome (IBS) patients based on quantitative real-time PCR analysis.AimsWe aimed to review the alterations in intestinal microbiota.MethodsAn online search up to June 9, 2016, was conducted. This systematic review and meta-analysis included differential expression of intestinal microbiota in patients with IBS versus healthy controls (HCs) and subgroup analysis. We assessed the quality of the included studies using an original assessment tool.ResultsA total of 13 articles involving 360 IBS patients and 268 healthy controls were included. The quality assessment scores for these articles ranged from 5 to 8. Significant differences in expression in IBS patients were observed for Lactobacillus (SMD = −0.85, P < 0.001, I² = 28%), Bifidobacterium (SMD = −1.17, P < 0.001, I² = 79.3%), and Faecalibacterium prausnitzii (SMD = −1.05, P < 0.001, I² = 0.0%) but not Bacteroides-Prevotella group, Escherichia coli or other genera or species. Subgroup analysis showed that diarrhea-predominant IBS patients had significantly different expression of Lactobacillus (SMD = −1.81, P < 0.001) and Bifidobacterium (SMD = −1.45, P < 0.001).ConclusionDown-regulation of bacterial colonization including Lactobacillus, Bifidobacterium and F. prausnitzii was observed in IBS patients, particularly in diarrhea-predominant IBS (IBS-D). Microbiota changes participate in the pathogenesis of IBS and may underlie the efficacy of probiotic supplements.     

Depression and resilience mediates the effect of family function on quality of life of the elderly

BackgroundFamily function, which improves individual resilience and strongly link to quality of life (QOL) among the elderly, increases the risk of depression. Because of these demonstrated relationships, it can be hypothesized that both depression and resilience are mediators of the association between family function and QOL.MethodsTo test this hypothesis, the structural equation model (SEM) constructed by Amos 21.0 was employed to assess the indirect effect of depression (Geriatric Depression Scale, GDS) and resilience (Connor-Davidson Resilience Scale, CD-RISC) on the relationship between family function (Family APGAR Score, APGAR) and QOL (12-item Short Form health survey, SF-12) in 474 elderly adults from three communities in Guangzhou, China.ResultsCorrelation matrix showed that depression is significantly negatively correlated with family functioning (r = −0.54, P < 0.01), resilience (r = −0.46, P < 0.01) and QOL (r = −0.63, P < 0.01), while resilience is significantly positively correlated with family functioning (r = 0.35, P < 0.01) and QOL (r = 0.40, P < 0.01). SEM indicated that Family functioning appeared to have significant indirect effects through resilience (β = 0.089) and depression (β = 0.307; combined β = 0.056) on QOL (R² = 0.55). The model fit indices showed a good fit of the model of the data (χ²/df = 1.362, P > 0.05, SRMR = 0.023, RMSEA = 0.028, GFI = 0.985, NFI = 0.987, TLI = 0.993, CFI = 0.996).ConclusionsThe finding supports the assumption that depression and resilience are consistent intermediary factors of the relationship between family function and QOL among the elderly.     

Radical cystectomy versus organ-sparing trimodality treatment in muscle-invasive bladder cancer: A systematic review of clinical trials

BackgroundRadical cystectomy (RC) represents the mainstay of treatment in patients with muscle-invasive urinary bladder cancer but how it compares with the best organ preservation approach is not known.Materials and methodsThe objective of our review is to compare the 5-year overall survival (OS) rates from retrospective and prospective studies of RC and trimodality treatment (TMT), i.e. concurrent delivery of chemotherapy and radiotherapy after a transurethral resection of bladder tumor (TURBT), involving a total of 10,265 and 3131 patients, respectively. We used random-effect models to pool outcomes across studies and compared event rates of combined outcomes for TMT and RC using an interaction test.ResultsThe median 5-year OS rate was 57% in the TMT group, when compared with 52% (P = 0.04), 51% (P = 0.02) and 53% (P = 0.38) in the whole group receiving RC or the group treated with RC alone or RC + chemotherapy, respectively. The hazard risk (HR) of mortality of patients treated with TMT or RC was 1.22 (95% CI = 1.13–1.32) with an absolute benefit of 5% in favor of the former. The HR of mortality from TMT persisted significantly better not only versus the group treated with RC alone (HR = 1.22; 95% CI = 1.12–1.32), but also versus the group receiving RC + chemotherapy (HR = 1.22; 95% CI = 1.09–1.36). Multivariate analysis confirmed TMT as a significant prognostic variable for both RC alone and RC + chemotherapy.ConclusionCompared with RC, TMT seems to be associated with a better outcome for patients with muscle-invasive bladder cancer (MIBC). The addition of chemotherapy may improve the RC outcome in some subgroups of patients with a higher probability of micrometastases. Prospective randomized trials are urged to verify these findings and better define the role of organ preservation and radical treatment strategy in the management of patients with MIBC.     

Study of the effects of transoral gastroplasty on insulin sensitivity and secretion in obese subjects

Background and aimsTransoral gastroplasty (TOGA) recently emerged as a new, feasible and relatively safe technique for the surgical treatment of obesity. However, so far there are no data on the effects on insulin sensitivity in the literature. Our aim is to evaluate the effect of TOGA on insulin sensitivity and secretion.Methods and resultsNine glucose normo-tolerant obese subjects (age:41 ± 6 years; BMI:42.49 ± 1.03 kg/m²) were studied. Fat-free mass (FM) and fat mass (FM) were assessed by bioelectrical impedance; plasma glucose, insulin, and C-peptide were measured during an oral glucose tolerance test (OGTT) before and 3 months after the operation. Insulin sensitivity was calculated using the oral-glucose insulin-sensitivity index, and insulin secretion by C-peptide deconvolution.Three months after surgery, a significant (P = 0.008) reduction of BMI to 35.65 ± 0.65 kg/m², with a decrease of FM and FFM from 57.22 ± 2.19 to 41.46 ± 3.02 kg (P = 0.008) and from 59.52 ± 1.36 to 56.67 ± 1.10 kg (P = 0.048) respectively, was observed. Insulinemia was significantly reduced at fast and at 120 min after OGTT; in contrast, no significant change in glucose concentration was observed. Insulin sensitivity significantly increased (348.45 ± 20.08 vs. 421.18 ± 20.84 ml/min/m², P = 0.038) and the incremental area of insulin secretion rate (total ISR) significantly decreased (from 235.05 ± 27.50 to 124.77 ± 14.50 nmol/min/m², P = 0.021). Total ISR correlated with weight, BMI and FM (r = 0.522, P = 0.028; r = 0.541, P = 0.020; r = 0.463, P = 0.049, respectively). BMI represented the most powerful predictor of ISR decrease (R² = 0.541, P = 0.020).ConclusionTransoral gastroplasty allows a significant weight loss 3 months after the intervention as well as an amelioration of insulin sensitivity with subsequent reduction of the insulin secretion.     

Relationship between circulating endothelial progenitor cells and insulin resistance in non-diabetic patients with ischemic chronic heart failure

AimThe objective of this study was to assess a relationship between insulin resistance (IR) and counts of CD45⁻CD34⁺, CD14⁺CD309⁺, and CD14⁺CD309⁺Tie2⁺ phenotyped circulating endothelial progenitor cells (EPCs) in patients with ischemic chronic heart failure (CHF).MethodsThe study involved 300 CHF patients (186 males) aged 48–62 years with angiografically proven coronary artery disease and/or previously defined myocardial infarction. Insulin resistance was assessed by the homeostasis model assessment for insulin resistance (HOMA-IR). EPC populations were phenotyped by flow cytofluorimetry.ResultsCirculating EPCs counts were statistically significantly lower in CHF patients with IR than in patients without IR. We found that the most valuable multivariable predictors of the depletion of the CD45⁺CD34⁺ EPCs were NT-pro-brain natriuretic peptide (BNP) (1.32; 95% CI = 1.19–2.77; P = 0.001), left ventricular ejection fraction (OR = 1.30; 95% CI = 1.09–1.60; P = 0.002), NYHA class (OR = 1.12; 95% CI = 1.02–1.19; P = 0.001). NT-pro-BNP (OR = 1.45; 95% CI = 1.15–2.90; P = 0.003), left ventricular ejection fraction (OR = 1.32; 95% CI = 1.11–1.65; P = 0.001) were found as powerful predictors for depletion in CD45⁻CD34⁺ EPCs. We also identified six independent variables with high predictive value for depletion of CD14⁺CD309⁺ EPCs: NT-pro-BNP (OR = 1.41; 95% CI = 1.15–2.90; P = 0.003), left ventricular ejection fraction (OR = 1.18; 95% CI = 1.10–1.76; P = 0.036), NYHA class (OR = 1.15; 95% CI = 1.07–1.22; P = 0.001), hs-C reactive protein (OR = 1.02; 95% CI = 1.01–1.05; P = 0.012). As independent multivariable predictors for depletion in CD14⁺CD309⁺Tie2⁺ EPCs were selected five variables: NT-pro-BNP (OR = 1.65; 95% CI = 1.44–4.70; P = 0.006), left ventricular ejection fraction (OR = 1.07; 95% CI = 1.02–1.12; P = 0.018), NYHA class (OR = 1.13; 95% CI = 1.06–1.21; P = 0.001), hs-C-reactive protein (OR = 1.08; 95% CI = 1.03–1.16; P = 0.002).ConclusionIR may be an additional factor contributing decreased circulating level of proangiogenic EPCs in non-diabetic CHF patients.     

Efficacy and Safety of Oral Conivaptan,a Vasopressin-Receptor Antagonist,Evaluated in a Randomized,Controlled Trial in Patients With Euvolemic or Hypervolemic Hyponatremia

BackgroundIn most cases of hyponatremia, arginine vasopressin secretion is inappropriately high. This placebo-controlled, randomized, double-blind multicenter study evaluated the efficacy and safety of oral conivaptan, a V_1A/V₂-receptor antagonist, in patients with euvolemic or hypervolemic hyponatremia.MethodsEighty-three patients with serum [Na⁺] less than 130 mEq/L were stratified by volume status and randomly assigned to placebo or conivaptan 40 or 80 mg/d for 5 days.ResultsConivaptan increased the baseline-adjusted area under the serum [Na⁺]-time curve significantly more than placebo (P = 0.0001). Patients given either dose of conivaptan demonstrated a serum [Na⁺] of 4 mEq/L or greater above baseline significantly faster than those given placebo (P < 0.001) and maintained that increase for a greater total time (P = 0.0001). The least squares mean change in serum [Na⁺] from baseline to end of treatment was also significantly greater with conivaptan 40 and 80 mg/d (6.8 and 8.8 mEq/L, respectively) (P = 0.0001) than that with placebo (1.2 mEq/L). The percentage of patients who obtained an increase from baseline in serum [Na⁺] of 6 mEq/L or greater or normal serum [Na⁺] was significantly higher among patients given conivaptan 40 and 80 mg/d (67% and 88%, respectively) than among those given placebo (20%; P < 0.001). Conivaptan was well tolerated; the most frequent adverse events were urinary tract infection, anemia, pyrexia, cardiac failure, hypotension, and hypokalemia.ConclusionOral conivaptan was effective in increasing serum [Na⁺] in patients with euvolemic or hypervolemic hyponatremia and had a favorable safety profile.     

Evaluación multiparamétrica de la función ventricular derecha en la hipertensión arterial pulmonar asociada a cardiopatías congénitas

Introduction and objectivesOutcome in patients with congenital heart diseases and pulmonary arterial hypertension (PAH) is closely related to right ventricular (RV) function. Two-dimensional echocardiographic parameters, such as strain imaging or RV end-systolic remodeling index (RVESRI) have emerged to quantify RV function.MethodsWe prospectively studied 30 patients aged 48 ± 12 years with pretricuspid shunt and PAH and investigated the accuracy of multiple echocardiographic parameters of RV function (tricuspid annular plane systolic excursion, tricuspid annular peak systolic velocity, RV systolic-to-diastolic duration ratio, right atrial area, RV fractional area change, RV global longitudinal strain and RVESRI) to RV ejection fraction measured by cardiac magnetic resonance.ResultsRV ejection fraction < 45% was observed in 13 patients (43.3%). RV global longitudinal strain (ρ [Spearman's correlation coefficient] = −0.75; P = .001; R² = 0.58; P = .001), right atrium area (ρ = −0.74; P < .0001; R² = 0.56; P < .0001), RVESRI (ρ = −0.64; P < .0001; R² = 0.47; P < .0001), systolic-to-diastolic duration ratio (ρ = −0.62; P = .0004; R² = 0.47; P < .0001) and RV fractional area change (ρ = 0.48; P = .01; R² = 0.37; P < .0001) were correlated with RV ejection fraction. RV global longitudinal strain, RVESRI and right atrium area predicted RV ejection fraction < 45% with the greatest area under curve (0.88; 95%CI, 0.71-1.00; 0.88; 95%CI, 0.76-1.00, and 0.89; 95%CI, 0.77-1.00, respectively). RV global longitudinal strain > −16%, RVESRI ≥ 1.7 and right atrial area ≥ 22 cm² predicted RV ejection fraction < 45% with a sensitivity and specificity of 87.5% and 85.7%; 76.9% and 88.3%; 92.3% and 82.4%, respectively.ConclusionsRVESRI, right atrial area and RV global longitudinal strain are strong markers of RV dysfunction in patients with pretricuspid shunt and PAH.     

Accuracy of computed tomography angiography in the detection of pulmonary embolism in patients with high body weight

BackgroundThe accuracy of CT pulmonary angiography (CTPA) in detecting or excluding pulmonary embolism has not yet been assessed in patients with high body weight (BW).MethodsThis retrospective study involved CTPAs of 114 patients weighing 75–99 kg and those of 123 consecutive patients weighing 100–150 kg. Three independent blinded radiologists analyzed all examinations in randomized order. Readers' data on pulmonary emboli were compared with a composite reference standard, comprising clinical probability, reference CTPA result, additional imaging when performed and 90-day follow-up. Results in both BW groups and in two body mass index (BMI) groups (BMI < 30 kg/m² and BMI ≥ 30 kg/m², i.e., non-obese and obese patients) were compared.ResultsThe prevalence of pulmonary embolism was not significantly different in the BW groups (P = 1.0). The reference CTPA result was positive in 23 of 114 patients in the 75–99 kg group and in 25 of 123 patients in the ≥ 100 kg group, respectively (odds ratio, 0.991; 95% confidence interval, 0.501 to 1.957; P = 1.0). No pulmonary embolism-related death or venous thromboembolism occurred during follow-up. The mean accuracy of three readers was 91.5% in the 75–99 kg group and 89.9% in the ≥ 100 kg group (odds ratio, 1.207; 95% confidence interval, 0.451 to 3.255; P = 0.495), and 89.9% in non-obese patients and 91.2% in obese patients (odds ratio, 0.853; 95% confidence interval, 0.317 to 2.319; P = 0.816).ConclusionThe diagnostic accuracy of CTPA in patients weighing 75–99 kg or 100–150 kg proved not to be significantly different.     

Disordered glycemic control in women with type 2 diabetes is associated with increased TNF receptor-2 levels

BackgroundEvidence implicates tumor necrosis factor (TNF) in the pathophysiology of Type 2 Diabetes (T2D) through unclear mechanisms. We hypothesized that disordered glycemic control leads to TNF activation and increases in soluble-TNF (sTNF) and its receptors-1 (sTNFR1) and -2 (sTNFR2).MethodsWe characterized 265 T2D and non-diabetic Latin American subjects and assessed the relationship between the TNF system and fasting plasma glucose (FPG), hemoglobin-A1C (A1C), insulin (FPI), C-peptide and HOMA-Beta.ResultssTNF and sTNFR2 but not sTNFR1 levels were higher in T2D than non-diabetics (P < 0.0001). In T2D, sTNFR2 was associated with A1C and C-peptide (R² = 0.354, b = 0.504, P < 0.0001; b = 0.167, P = 0.049). Also, T2D patients with disordered glycemic control had increased sTNFR2 levels that correlated with FPG (Rho:0.393, P < 0.001), A1C (Rho:0.451, P < 0.001) and HOMA-Beta (Rho:-0.308, P = 0.005); events not observed in T2D patients with adequate glycemic control. Furthermore, sex-based comparative analyses of T2D patients showed that women compared to men had higher sTNFR2 levels (P = 0.017) that correlated with FPG, A1C, FPI and HOMA-Beta.ConclusionsDisordered glycemic control is associated with sTNF and sTNFR2. sTNFR2 levels were higher in T2D women than men. Thus, increased sTNFR2 levels may be an important biomarker for disordered glucose and inflammatory complications in T2D patients and women in particular.     

Lymphœdème des membres inférieurs : une manifestation rare des spondyloarthrites

IntroductionSpondyloarthritis include articular (axial, peripheral or enthesitic) and extra-articular manifestations. We reported three cases of limb lymphedema associated with a spondyloarthritis.Case reportsWe report on two men and one female aged of 75, 52 and 39 years, respectively. The rheumatic disease was an ankylosing spondylitis HLA B27 positive in two patients and a psoriatic arthritis in the remaining one. Lymphedema, always unilateral, confirmed by the Stemmer's sign, involved the whole lower limb (n = 2) or only the foot and calf (n = 1). Lymphedema occurred 3 months, 40 and 9 years after the onset of spondyloarthritis. Lower limb lymphoscintigraphy was abnormal in all cases: decrease (n = 2) or absence (n = 1) of inguinal lymph node uptake, and visualization of the popliteal lymph node related to deep lymphatic pathway (n = 1). Treatment of the spondyloarthritis did not improve lymphedema. Both the low-stretch bandage and elastic compression treatment allowed its reduction and stabilization.ConclusionLimb lymphedema is a rare extra-articular manifestation of spondyloarthritis. Its course appears to be independent of joint disease. Its management is specific and should be associated to that of the rheumatologic disorder.     

Does DRD2 polymorphism influence the clinical characteristics of prolactinoma?

ObjectivesGenetic alterations explaining the clinical variability of prolactinomas still could not be clarified and dopamine D2 receptor (DRD2) polymorphism is a putative candidate for the variable response to dopaminergic treatment. The present study was conducted to investigate the influence of DRD2 TaqI A polymorphism on initial and follow-up characteristics of prolactinoma.Patients and methodsSeventy-two patients with prolactinoma and 98 age and gender matched control subjects were recruited to the case-control study. Serum prolactin levels were assessed by enzyme-linked immunosorbent assay and DRD2 polymorphism was determined by polymerase chain reaction and restriction length polymorphism analysis.ResultsDecrease of prolactin levels and the tumor shrinkage after cabergoline treatment were 93.9 ± 5.9% and 58.3 ± 33.1% in microadenomas and 96.1 ± 6.1% and 51.7 ± 29.3 in macroadenomas (P = 0.02 and P > 0.05, respectively). We observed no significant difference for DRD2 genotypes and the alleles between the patients and healthy group (P > 0.05). Prolactin levels before treatment were correlated with tumor diameter before and after treatment and the percentage of prolactin decrease with treatment (P < 0.001 r = 0.58, P < 0.001 r = 0.40 and P < 0.001 r = 0.47, respectively). Tumor diameter before the treatment was also correlated with the tumor diameter after the treatment (P < 0.001 r = 0.64) and the percentage of prolactin decrease (P = 0.01 r = 0.30). However, no significant association was found between characteristics of prolactinoma and DRD2 genotypes and alleles (P > 0.05).ConclusionThis study revealed that DRD2 TaqI A receptor polymorphism was not associated with the development of prolactinoma and its clinical characteristics. Future studies are needed to clarify the clinical implications of genetic alterations in prolactinoma.     

Heart failure and chronic kidney disease in a registry of internal medicine wards

BackgroundThe aim of the present study was to evaluate the association between heart failure (HF) and chronic kidney disease (CKD) in tertiary care centers using the clinical records of patients enrolled in internal medicine departments.Patients and methodsWe used the clinical records of 1380 elderly patients to identify patients with a history of HF and CKD using admission ICD codes and glomerular filtration rate (GFR) formulas. Magnitude and strength of such associations were investigated by univariable and multivariable analysis.ResultsOf the 1380 patients enrolled, 27.9% had HF (age 80 ± 7, BMI 27 ± 6 kg/m²) and 17.4% CKD (age 81 ± 7, BMI 26.8 ± 6 kg/m²). Both groups were significantly older (P < 0.0001) with BMI higher than the patients without those diagnosis (P < 0.02). Patients with a history of CKD showed higher non-fasting glycaemia (140 ± 86 vs. 125 ± 63 mg/dL, P < 0.001). CKD was significantly associated with HF (P < 0.0001). Patients with HF had an estimated GFR lower than patients without HF (P < 0.0001). Comorbidity and severity indices were significantly higher in subjects with HF (P < 0.0001) and CKD (P < 0.0001) than in those without. Multivariable analysis showed a significant association between HF and age (for five years increase OR 1.13, P < 0.009), BMI (for each 3 kg/m² increase OR 1.15, P < 0.001), GFR (for each decrease of 10 mL/min increase OR 0.92, P < 0.002) and severity index (IS) (for each 0.25 units increase OR 1.43, P < 0.001).ConclusionHF on admission is strongly associated with CKD, older age, BMI, and SI. These data focus the value of epidemiological studies such REPOSI in identifying and monitoring multimorbidity in elderly.     

Field performance of the Abbott RealTime MTB assay for the diagnosis of extrapulmonary tuberculosis in a low-prevalence setting

IntroductionThe sensitivities of conventional mycobacterial culture in solid or liquid media and acid-fast bacilli (AFB) smear microscopy for Mycobacterium tuberculosis complex (MTBC) detection in extrapulmonary specimens are suboptimal. We evaluated the field performance of the Abbott RealTime MTB assay for the diagnosis of extrapulmonary tuberculosis in a low-prevalence setting.MethodsThe total number of extrapulmonary specimens with mycobacterial culture and PCR results was 566: sterile fluids (n = 278), non-sterile fluids (n = 147), lymph node material (n = 69) tissue biopsies (n = 63), and abscess aspirates (n = 9). A composite standard consisting of mycobacterial culture results, clinical treatment response to anti-TB drugs, when administered, and histopathology, radiological and laboratory findings were used as a reference for sensitivity and specificity calculations.ResultsMycobacterial cultures and PCR were positive in 17 and 28 specimens, respectively. The overall agreement between culture and PCR was moderate (Cohen's kappa coefficient: 0.549; P = 0.0001). Taking as a reference our composite standard, the sensitivity of the Abbott PCR assay was 77.7%, the specificity 99.5%, the PPV 95.4%, and the NPV 98.8%. In turn, the sensitivity of the mycobacterial culture was 62.9%, the specificity and PPV 100%, and the NPV 97.9%.ConclusionThe good field performance of the Abbott RealTime MTB assay makes it valuable for the diagnosis of extrapulmonary tuberculosis in a low-prevalence setting. The use of molecular methods along with culture improves the diagnosis of extrapulmonary tuberculosis.     

Effect of maternal lifestyle intervention on metabolic health and adiposity of offspring: Findings from the Finnish Gestational Diabetes Prevention Study (RADIEL)

AimTo assess in women at high risk of gestational diabetes mellitus (GDM) the effect of a lifestyle intervention on the metabolic health of their offspring around 5 years after delivery.MethodsFor the original Finnish gestational diabetes prevention study (RADIEL), 720 women with a prepregnancy body mass index (BMI) ≥ 30 kg/m² and/or previous GDM were enrolled before or during early pregnancy and allocated to either an interventional (n = 126) or conventional (n = 133) care group. The present 5-year follow-up substudy assessed the metabolic health outcomes of their offspring. Age- and gender-standardized residuals of metabolic health components (waist circumference, mean arterial pressure, high-density lipoprotein and triglyceride levels, and fasting insulin/glucose ratio) were also combined to determine the accumulation of metabolic effects. Body composition was assessed by electrical bioimpedance.ResultsOffspring of women in the intervention group had a less optimal metabolic profile after the 5-year follow-up compared with offspring in the usual care group (P = 0.014). This difference in metabolic health was primarily related to lipid metabolism, and was more prominent among boys (P = 0.001) than girls (P = 0.74). Neither GDM, gestational weight gain, prepregnancy BMI, offspring age nor timing of randomization (before or during pregnancy) could explain the detected difference, which was also more pronounced among the offspring of GDM pregnancies (P = 0.010). Offspring body composition was similar in both groups (P > 0.05).ConclusionThe lifestyle intervention aimed at GDM prevention was associated with unfavourable metabolic outcomes among offspring at around 5 years of age.