Plasma copeptin concentration and outcome after pediatric traumatic brain injury

Higher plasma copeptin level has been associated with poor outcomes of critical illness. The present study was undertaken to investigate the plasma copeptin concentrations in children with traumatic brain injury (TBI) and to analyze the correlation of copeptin with disease outcome. Plasma copeptin concentrations of 126 healthy children and 126 children with acute severe TBI were measured by enzyme-linked immunosorbent assay. Twenty-one patients (16.7%) died and 38 patients (30.2%) had an unfavorable outcome (Glasgow Outcome Scale score of 1–3) at 6 months. Plasma copeptin level was obviously higher in patients than in healthy children (46.2 ± 20.8 pmol/L vs. 9.6 ± 3.0 pmol/L, P < 0.001). Plasma copeptin level was identified as an independent predictor for 6-month mortality [odds ratio (OR) 1.261, 95% confidence interval (CI) 1.112–1.538, P = 0.005] and unfavorable outcome (OR 1.313, 95% CI 1.146–1.659, P = 0.003). The predictive value of copeptin was similar to that of Glasgow Coma Scale (GCS) score for 6-month mortality [area under curve (AUC) 0.832, 95% CI 0.755–0.892 vs. AUC 0.873, 95% CI 0.802–0.926, P = 0.412] and unfavorable outcome (AUC 0.863, 95% CI 0.790–0.918 vs. AUC 0.885, 95% CI 0.816–0.935, P = 0.596). Copeptin improved the AUC of GCS score for 6-month unfavorable outcome (AUC 0.929, 95% CI 0.869–0.967, P = 0.013), but not for 6-month mortality (AUC 0.887, 95% CI 0.818–0.936, P = 0.600). Thus, plasma copeptin level represents a novel biomarker for predicting 6-month clinical outcome in children with TBI.     

Plasma visfatin,a possible prognostic marker in aneurysmal subarachnoid hemorrhage

Visfatin is linked to inflammation and associated with clinical outcomes of intracerebral hemorrhage. This study was designed to investigate whether visfatin might serve as a marker of severity and prognosis in aneurysmal subarachnoid hemorrhage. In this study, plasma visfatin levels of 172 consecutive patients and 172 sex and age-matched healthy subjects were determined using enzyme-linked immunosorbent assay. The recorded clinical outcomes included in-hospital mortality and 6-month mortality and unfavorable outcome (Glasgow Outcome Scale score of 1–3). Plasma visfatin level was substantially higher in patients than in healthy controls (92.1 ± 20.5 ng/mL vs. 12.4 ± 3.2 ng/mL; P < 0.001), was significantly associated with the World Federation of Neurological Surgeons (WFNS) score (r = 0.569, P < 0.001) and Fisher score (r = 0.657, P < 0.001), was an independent predictor of in-hospital mortality [odds ratio (OR), 1.378; 95% confidence interval (CI), 1.036–1.866; P = 0.002] and 6-month mortality (OR, 1.261; 95% CI, 1.018–1.745; P = 0.004) and unfavorable outcome (OR, 1.207; 95% CI, 1.012–1.682; P = 0.008) in multivariate logistic regression analysis and had high predictive value for in-hospital mortality [area under curve (AUC), 0.849; 95% CI, 0.787–0.899; P < 0.001] and 6-month mortality (AUC, 0.868; 95% CI, 0.808–0.915; P < 0.001) and unfavorable outcome (AUC, 0.859; 95% CI, 0.797–0.907; P < 0.001) using receiver operating characteristic curves. AUCs of visfatin were similar to those of WFNS score and Fisher score (all P > 0.05), but visfatin did not improve the predictive values of WFNS score and Fisher score (all P > 0.05). Thus, visfatin may be associated with clinical severity of aneurysmal subarachnoid hemorrhage and also have prognostic value for clinical outcomes.     

Relationship between plasma copeptin levels and complications of community-acquired pneumonia in preschool children

High plasma copeptin level has been associated with clinical outcomes after acute illness. The present study was undertaken to investigate the plasma copeptin concentrations in preschool children with community-acquired pneumonia (CAP) and to analyze the correlations of copeptin with CAP-related complications and pleural effusion. Plasma copeptin concentrations of 100 healthy children and 165 preschool children with CAP were measured. 35 children (21.2%) presented with complicated CAP and 28 children (17.0%) presented with pleural effusion. The admission copeptin levels were significantly increased in all patients (49.7 ± 21.4 pmol/L), children with complicated CAP (73.0 ± 16.9 pmol/L), those with uncomplicated CAP (43.4 ± 17.8 pmol/L), those with pleural effusion (70.9 ± 17.4 pmol/L) and those without pleural effusion (45.3 ± 19.5 pmol/L) compared with healthy control individuals (9.0 ± 2.7 pmol/L, all P < 0.001). Multivariate logistic regression analysis showed that plasma copeptin levels were independently related to CAP-related complications (odds ratio 1.214, 95% confidence interval 1.104–1.872, P < 0.001) and pleural effusion (odds ratio 1.226, 95% confidence interval 1.109–1.917, P < 0.001). A receiver operating characteristic curve analysis showed plasma copeptin level better predicted CAP-related complications (area under curve 0.876, 95% confidence interval 0.815–0.922) and pleural effusion (area under curve 0.831, 95% confidence interval 0.765–0.885). Thus, plasma copeptin level may represent a novel biomarker for predicting CAP-related complications in preschool children.     

Prediction of all-cause mortality with copeptin in cardio-cerebrovascular patients: A meta-analysis of prospective studies

BackgroundMeasurement of the biomarker copeptin may help identify disease severity and risk of mortality for a various diseases. This study sought to determine the relationship between copeptin and all-cause mortality of patients with cardio-cerebrovascular disease.MethodsDatabase of Medline and Web of Science were searched for studies with data involving the baseline copeptin levels and subsequent all-cause mortality outcomes. The pooled HRs of all-cause mortality were calculated and presented with 95%CIs. Subgroup analysis and sensitivity analysis were conducted to explore the possible sources of heterogeneity.ResultsData from 14,395 participants were derived from 28 prospective studies. Higher copeptin significantly increased the risk of all-cause mortality (per unit copeptin: HR = 1.020, 95%CI = 1.004–1.036; log unit copeptin: HR = 2.884, 95%CI = 1.844–4.512; categorical copeptin: HR = 3.371, 95%CI = 2.077–5.472). Subgroup analysis indicated that the risk of all-cause death was higher in cerebrovascular patients (per unit copeptin: HR = 2.537, 95%CI = 0.956–6.731; log unit copeptin: HR = 3.419, 95%CI = 2.391–4.888) than cardiovascular patients (per unit copeptin: HR = 1.011, 95%CI = 1.002–1.020; log unit copeptin: HR = 2.009, 95%CI = 1.119–3.608).ConclusionCopeptin is associated with all-cause mortality of patients with cardiovascular and cerebrovascular disease. Our study suggests that copeptin seems to be a promising novel biomarker for prediction of mortality in cardio-cerebrovascular patients, especially for cerebrovascular patients.     

Association of p53 and MDM2 polymorphisms with risk of human papillomavirus (HPV)-related esophageal squamous cell carcinoma (ESCC)

PurposeThough polymorphisms of the tumor suppressor gene p53 have been extensively investigated in numerous tumors, particularly tumors associated with human papillomavirus (HPV) infection. However, the results remain controversial. Our previous study showed that HPV serostatus is not an independent risk factor for esophageal squamous cell carcinoma (ESCC) in nonsmokers and nondrinkers. Given the roles of p53 and HPV E6 as well as MDM2 oncoproteins in p53 degradation, we validated the association of p53 and MDM2 polymorphisms with ESCC risk stratified by HPV16 sero-status.MethodsSingle nucleotide polymorphisms of p53 Arg72Pro (rs1042522) and MDM2 (rs937283) in 307 ESCC patients and 311 healthy controls were genotyped. The presence or absence of HPV16 in serum was measured by enzyme-linked immunosorbent assay. Multivariable logistic regression analysis was used to evaluate the possible associations of p53 and MDM2 polymorphisms with ESCC risk stratified by HPV16 sero-status.ResultsPatients carrying p53 Arg/Arg or Arg/Pro had a higher risk of esophageal SCC (P < 0.001, Odds ratio [OR] 4.98, 95% confidential interval [CI] 3.46–7.17), however, not found in MDM2 rs937283. The risk of esophageal SCC increased significantly among patients carrying p53 Arg/Arg, or Arg/Pro and HPV16-seropositivity (P < 0.001, OR 9.33, 95% CI 5.44–16.0), but not for MDM2 rs937283. The risk of esophageal SCC was further elevated among patients carrying Arg/Arg or Arg/Pro and HPV16-seropositivity who were smokers (P < 0.001, OR 27.05, 95% CI 11.06–66.16) or drinkers (P < 0.001, OR 13.20, 95% CI 5.74–30.38).ConclusionHPV16 seropositivity synergized with p53 Arg/Arg or Arg/Pro and increased ESCC risk, especially in smokers or drinkers.     

Low plasma leptin level at admission predicts delirium in critically ill patients: A prospective cohort study

The pathophysiology of delirium remains poorly understood. Low leptin level has been associated with features leading to delirium such as dysregulated immune functions and loss of neuroprotective effects. The purpose of the present study was to investigate the relationship between plasma leptin level at intensive care unit (ICU) entry and subsequent occurrence of delirium in critically ill patients. This single-center prospective cohort study in China allocated 336 critically ill patients admitted to ICU between 05/2015 and 05/2016 into a delirium group (n = 102) and non-delirium group (n = 234) based on whether delirium occurred during their stay at the ICU. Patients were examined at least twice daily and delirium was diagnosed using the Confusion Assessment Method for the ICU (CAM-ICU). Blood samples were obtained after ICU entry. Plasma leptin concentrations were measured by ELISA. Delirium occurred in 30.4% (102/336) of patients. Patients who developed delirium showed significantly lower leptin level at ICU entry than those who did not (6.1 ± 3.2 vs. 9.2 ± 5.9 ng/mL; P < 0.001). Low plasma leptin level at ICU entry was independently associated with subsequent occurrence of delirium (OR, 0.865; 95%CI, 0.802–0.934; P < 0.001). Other independent risk factors for delirium included increasing age (OR, 1.050; 95%CI, 1.020–1.080; P = 0.001) and Acute Physiology and Chronic Health Evaluation-II (APACHE-II) score (OR, 1.148; 95%CI, 1.092–1.208; P < 0.001). Patients who developed delirium had a prolonged duration of ICU stay and higher mortality. Low plasma leptin level at ICU entry was associated with the occurrence of delirium in critically ill patients.     

Childhood passive smoke exposure is associated with adult head and neck cancer

Introduction: Passive smoke is carcinogenic but its association with head and neck squamous cell carcinoma (HNSCC) is uncertain. Methods: We conducted a case-control study of childhood passive smoke exposure (CPSE) and HNSCC in 858 cases and 806 frequency-matched controls using an interviewer-administered questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated with logistic regression controlling for adult smoking in the total study population, and in never-smokers only (184 cases and 415 controls). CPSE was also studied in oropharyngeal separately from other HNSCC using polytomous logistic regression. Results: CPSE was associated with HNSCC (OR, 1.28; 95% CI, 1.01–1.63) after controlling for adult smoking and other factors. This association was similar in magnitude, although not statistically significant, among subjects who never smoked as adults (OR, 1.19, 95% CI, 0.80–1.76). CPSE was associated more strongly with oropharyngeal cancer (a HNSCC subtype commonly associated with human papillomavirus (HPV) infection) than with HNSCC at non-oropharyngeal sites (OR, 2.02; 95% CI, 1.01–4.06, N = 52 cases vs. OR, 1.04; 95% CI, 0.68–1.60, N = 132 cases; P-for-heterogeneity = 0.08). Conclusions: Data from this large US-based case control study suggest a role for CPSE in HNSCC etiology.     

Community-acquired infections and their association with myeloid malignancies

Introduction: Antigenic stimulation is a proposed aetiologic mechanism for many haematological malignancies. Limited evidence suggests that community-acquired infections may increase the risk of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS). However, associations with other myeloid malignancies including chronic myeloid leukaemia (CML) and myeloproliferative neoplasms (MPNs) are unknown. Materials and methods: Using the Surveillance, Epidemiology and End Result (SEER)-Medicare database, fourteen community-acquired infections were compared between myeloid malignancy patients [AML (n = 8489), CML (n = 3626) diagnosed 1992–2005; MDS (n = 3072) and MPNs (n = 2001) diagnosed 2001–2005; and controls (200,000 for AML/CML and 97,681 for MDS/MPN]. Odds ratios (ORs) and 95% confidence intervals were adjusted for gender, age and year of selection excluding infections diagnosed in the 13-month period prior to selection to reduce reverse causality. Results: Risk of AML and MDS respectively, were significantly associated with respiratory tract infections, bronchitis (ORs 1.20 [95% CI: 1.14–1.26], 1.25 [95% CI: 1.16–1.36]), influenza (ORs 1.16 [95% CI: 1.07–1.25], 1.29 [95% CI: 1.16–1.44]), pharyngitis (ORs 1.13 [95% CI: 1.06–1.21], 1.22 [95% CI: 1.11–1.35]), pneumonia (ORs 1.28 [95% CI: 1.21–1.36], 1.52 [95% CI: 1.40–1.66]), sinusitis (ORs 1.23 [95% CI: 1.16–1.30], 1.25 [95% CI: 1.15–1.36]) as was cystitis (ORs 1.13 [95% CI: 1.07–1.18], 1.26 [95% CI: 1.17–1.36]). Cellulitis (OR 1.51 [95% CI: 1.39–1.64]), herpes zoster (OR 1.31 [95% CI: 1.14–1.50]) and gastroenteritis (OR 1.38 [95% CI: 1.17–1.64]) were more common in MDS patients than controls. For CML, associations were limited to bronchitis (OR 1.21 [95% CI: 1.12–1.31]), pneumonia (OR 1.49 [95% CI: 1.37–1.62]), sinusitis (OR 1.19 [95% CI: 1.09–1.29]) and cellulitis (OR 1.43 [95% CI: 1.32–1.55]) following Bonferroni correction. Only cellulitis (OR 1.34 [95% CI: 1.21–1.49]) remained significant in MPN patients. Many infections remained elevated when more than 6 years of preceding claims data were excluded. Discussion: Common community-acquired infections may be important in the malignant transformation of the myeloid lineage. Differences in the aetiology of classic MPNs and other myeloid malignancies require further exploration.     

TEP/TDM 18F-choline dans les récidives biologiques des cancers de la prostate traites par radiothérapie externe ou curiethérapie : impact du PSA et de sa cinétique

AimTo determine the impact of PSA and its kinetics on ¹⁸F-Choline PET/CT (FCH PET) ability to detect site of relapse in prostate cancer initially treated with external beam radiotherapy (EBRT) or brachytherapy (IBT).MethodsWe retrospectively enrolled PET FCH performed for suspicion of biochemical relapse after EBRT/IBT from January 2010 to January 2017 at Institut Curie. PSA_trigger, ΔPSA_nadir (PSA_trigger-PSA_nadir), PSA doubling time (PSA_dt) and velocity (PSA_vel) were compared between positive and negative results. Logistic regression analysis was used to determine the relationship between these parameters and PET ability to detect True Positives (TP).ResultsIn all, 271 FCH PET met the inclusion criteria: 169 after treatment with EBRT and 102 after IBT. Positivity rate was 67.9%, and 63.4% of TP were local relapses. Overall sensitivity and specificity were 81.2% and 71.0%. PSA_trigger was 3.32 ng/mL (interquartile space: IQS 2.28–5.77) when PET was negative and 5.15 ng/mL (IQS 3.16–10.17) when positive, ΔPSAnadir was respectively 2.76 ng/mL (IQS 1.84–4.69) and 4.57 ng/mL (IQS 2.48–8.85), PSA_dt 10.78 months (IQS 5.46–20.07) and 7.23 months (EI 2.58–14.14), and PSA_vel 2.16 ng/mL/year (EI 1.02–4.80) et 4.92 ng/mL/year (1.89–16.02) (P < 0.001). Positivity rate increased with PSA_trigger and ΔPSA_nadir. We found PSA_dt ≤ 9 months (P = 0.029; OR = 2.97, IC_95% [1.12–7.88]) and ΔPSA_nadir ≥ 3 ng/mL (P = 0.03; OR = 2.56, IC_95% [1.37–4.77]) to be independent predictive factors of PET sensitivity.ConclusionDetection of relapse after EBRT or IBT with PET FCH is influenced by PSA and its kinetics. In our study, PSA_dt and ΔPSA_nadir were independant predictors of PET performance, but initial treatment and tumor characteristics were not.     

Malignant pleural mesothelioma incidence and survival in the Republic of Ireland 1994–2009

ObjectiveMalignant pleural mesothelioma (MPM) is a rare malignancy associated with exposure to asbestos. The protracted latent period of MPM means that its incidence has continued to rise across Europe after the introduction of restrictions on asbestos use. In order to obtain a clearer indication of trends in the Republic of Ireland (ROI), incidence and survival were assessed based on all MPM cases reported since the establishment of the National Cancer Registry of Ireland (NCR).MethodsNCR recorded 337 MPM diagnoses in the ROI during 1994–2009. Survival was assessed for all cases diagnosed with adequate follow-up (n = 330). Crude and European age-standardized incidence rates were calculated for all cases and for 4-year periods. A Cox model of observed (all-cause) survival was used to generate hazard ratios for the effect of: gender; age at diagnosis; diagnosis cohort; region of residence; histological type; and tumour stage. Single P-values for the variables indicated were calculated using either a stratified log-rank test or stratified trend test.ResultsOver the study period the age-standardized MPM incidence in the ROI rose from 4.98 cases per million (cpm) to 7.24 cpm. The 1-year survival rate for all MPM cases was 29.6% (CI 24.7–34.6%). Excess mortality risk was associated with age at diagnosis (75–89 yrs vs. 55–64 yrs, HR 1.88, 95% CI 1.35–2.63, P < 0.001) and tumour stage (III vs. I HR 1.57, 95% CI 1.00–2.48, P < 0.05; IV vs. I HR 1.55, 95% CI 1.08–2.21, P < 0.05). Age showed a significant survival trend (P < 0.001) but tumour stage did not (P = 0.150). There was significant heterogeneity between the survival of patients resident in different regions (P = 0.027).ConclusionMPM incidence and mortality continued to rise in the ROI after the restrictions on asbestos use and the predictors of survival detected in this study are broadly consistent with those identified for other countries.     

The characterization and potential impact of melanoma cases with unknown thickness in the United States’ Surveillance,Epidemiology, and End Results Program, 1989–2008

Background: In the United States, the Surveillance, Epidemiology, and End Results (SEER) Program is the authoritative source for population-based data on melanoma incidence and mortality. However, missing data on tumor thickness may lead to biased analyses in this frequently used database. We sought to characterize invasive melanomas with unknown thickness with emphasis on their association with melanoma survival, and to employ techniques to overcome the limitations of missing data on tumor thickness. Methods: We conducted a retrospective cohort analysis of non-occult invasive melanomas in the SEER database from 1989 to 2008. Results: Of 182 184 cases, 24 329 (13%) had unknown thickness. From 1989–1993 to 2004–2008, the proportion of unknown thickness cases decreased from 22% to 9% (P_trend < 0.001). Unknown thickness cases had a significantly increased risk of death due to melanoma (hazard ratio [HR] 3.09, 95% confidence interval [CI]: 2.99, 3.19) than known thickness cases with an increasing trend over time (P_trend < 0.001). In multivariate analysis, unknown thickness was found to be independently associated with poorer prognostic factors and lack of cancer-directed surgical treatment. Melanoma survival of cases with unknown thickness appeared most similar to 2.01–4.00 mm thickness cases. Multiple imputation demonstrated that imputed tumor thickness was significantly associated with melanoma survival (HR 1.31, 95% CI: 1.30, 1.32) and Clark level (odds ratio [OR] 1.85, 95% CI: 1.82, 1.89) though the strength of associations were not as strong as the associations of original SEER-coded known tumor thickness with melanoma survival (HR 1.46, 95% CI: 1.45, 1.47) and Clark level (OR 2.92, 95% CI 2.89, 2.95), respectively. Conclusions: Exclusion of missing data on melanoma thickness from SEER introduces a selection bias that leads to an underestimation in the prevalence of fatal and likely thicker melanomas. Multiple imputation appears to be an effective tool to predict missing tumor thickness data.     

Association of Soluble (Pro) Renin Receptor with Gestational Diabetes Mellitus

ObjectiveThere is a need to identify biomarkers for gestational diabetes mellitus (GDM). Recently the soluble pro-renin receptor (s[Pro]RR) has been shown to be associated with GDM. We investigated the association of s(Pro) RR levels in Asian Indians with GDM.MethodsWe recruited 222 pregnant females, 147 without GDM (non-GDM) and 75 with GDM visiting antenatal clinics in Tamilnadu in South India. We included singleton pregnancy and excluded those with pre-existing diabetes mellitus or hypertension. Oral glucose tolerance tests (OGTTs) were performed, and GDM was diagnosed using the International Association of Diabetes and Pregnancy Study Group criteria. s(Pro)RR was measured by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curves were used to identify s(Pro) RR cut-off points to identify GDM.ResultsThe mean levels of the s(Pro)RR were significantly higher in subjects with GDM (34.0 ± 12 ng/mL, P < .001) compared to non-GDM (21.4 ± 6.5 ng/mL). The proportions of subjects with GDM were 11 (15%) in the first tertile of s(Pro)RR (< 19.61 ng/mL), 20 (27%) in the second (19.62-26.8 ng/mL), and 44 (59%) in the third tertile (> 26.8 ng/mL). In multiple logistic regression analysis, s(Pro)RR showed a significant association with GDM (odds ratio [OR]: 1.201, 95% confidence interval [CI]: 1.065-1.355, P = .003) after adjusting for potential con-founders. A s(Pro)RR cut-off of 23.3 ng/mL had a C statistic of 0.828 (95% CI: 0.738-0.918, P < .001), sensitivity of 68%, and specificity of 70% to identify GDM.Conclusionss(Pro)RR levels are higher in females with GDM, and this could be used as a potential biomarker. (Endocr Pract. 2015;21:7-13)     

HapMap-based study identifies risk sub-region on chromosome 19q13.3 in relation to lung cancer among Chinese

Background: Chromosome 19q13.3 has been identified as one of the regions that associate with cancer risk in previous studies. Methods: We systematically examined the 70.772 kb region comprising four genes on chromosome 19q13.3 among Chinese using the haplotype-tagging SNP (htSNP) approach and the HapMap platform. The study involved 339 lung cancer cases and 358 non-cancer controls. Two htSNPs (rs1046282 and rs735482) captured most of the common haplotypes of CD3EA and the combined effects of sixteen htSNPs provided high coverage of common haplotypes of ERCC2, PPP1R13L, CD3EAP and ERCC1. Results: Both carriers of variant CC genotype [adjusted OR (95% CI) = 1.28 (1.02–1.60), P = 0.04] and variant C-allele among >20 years’ smokers [OR (95% CI) = 2.13 (1.24–3.67), P = 0.006] for CD3EAP rs735482 were at increased risk of lung cancer. Four haplotype blocks of strong linkage disequilibrium were identified. The haplotype ERCC2 rs3916874^G and rs238415^C [OR (95% CI) = 1.26 (1.02–1.57), P = 0.03] in block 1 and the haplotype PPP1R13L rs4803817^A, CD3EAP rs1046282^T, rs735482^C, ERCC1 rs3212980^A, rs3212964^G [OR (95% CI) = 3.56 (1.55–8.18), P = 0.005] in block 3 were associated with lung cancer risk. MDR (multifactor dimensionality reduction) analysis demonstrated the best significant model of two-attributes containing smoking duration and rs2298881 in ERCC1 (P = 0.004–0.005) and suggested that the effects of high-order interactions among smoking duration and ERCC2, PPP1R13, ERCC1 htSNPs could modulate lung cancer risk. Conclusions: HapMap-based study of 19q13.3 identified that genetic variation of CD3EAP and two loci were associated with lung cancer risk and interaction of smoking duration and genetic variants was the strongest predictor of lung cancer risk in a Chinese population.     

Impact of HLA-class I alleles on response to HCV treatment in a cohort of Egyptian patients

Extensive allele diversity is observed in HLA associations with response to HCV combined therapy (pegylated interferon + ribavitin) in different global ethnic populations. The aim of the study is to assess the frequency and association of certain HLA-class I alleles in Egyptian persons with persistent HCV and others with sustained viral response (SVR).Material and methodsThe study was a retrospective cohort study that included 246 HCV patients who received combined therapy; 106 cases responded to treatment (SVR) and 140 individuals did not respond to treatment (persistent HCV infection). Both groups are subjected to genotyping for HLA-class I.ResultsAccording to logistic regression analysis, Cw17 was considered as the most predictor allele as it was the highest significant allele (OR = 16.70; 95% CI: 2.64–105.58; P = 0.003), whereas the presence of the HLA-B45 and HLA-B27 alleles has a 19.35-fold risk and 15.7 fold risk, respectively of non-response to interferon therapy in chronic HCV patients (OR = 19.35; 95% CI: 1.05–357.24; P = 0.04) and (OR = 15.69; 95% CI: 1.179–208.9; P = 0.04) can act also as high predictor alleles, and the lowest significant predictor allele was B44 (OR = 6.535; 95% CI: 1.55–27.63; P = 0.01). The presence of the HLA-A alleles might have a limited role in prediction for the non-responders, as the A32 was significantly higher among the SVR patients, but, it cannot have a predictor role (OR: 0.161, CI: 0.03–1.056, P = 0.049).ConclusionCw17, HLA-B45, and HLA-B27 alleles can predict the nonresponders to HCV combined therapy.     

The association between genetic damage in peripheral blood lymphocytes and polymorphisms of three glutathione S-transferases in Chinese workers exposed to 1,3-butadiene

1,3-Butadiene (BD) has been classified as a human carcinogen, group I; however, the relationship between polymorphisms of glutathione S-transferases that metabolize BD and chromosomal damage is not clear. The present study used sister chromatid exchange (SCE) and cytokinesis-block micronucleus (CBMN) assays to detect chromosomal damage in peripheral lymphocytes of 44 BD-exposed workers and 39 non-exposed healthy controls. PCR and PCR-RFLP were employed to detect three known glutathione S-transferase polymorphisms GSTT1, GSTM1, and GSTP1 (Ile105Val). The data demonstrated that the micronucleus (CBMN) frequency in BD-exposed workers was significantly higher than that in controls (frequency ratio (FR) = 1.48, 95% CI: 1.14–1.91, P < 0.01), and the CBMN frequency was higher in workers exposed to higher cumulative BD levels (FR = 1.70, 95% CI: 1.28–2.27, P < 0.01). However, differences in SCE frequency were not observed (FR = 1.14, 95% CI: 0.81–1.61, P > 0.05). Among exposed workers, chromosomal damage was related to BD exposure levels (FR = 1.35, 95% CI: 1.02–1.80, P < 0.05); age, older workers exhibited higher MN frequencies than younger workers (FR = 1.45, 95% CI: 1.14–1.84, P < 0.05); and years of work, those with more years of work exhibited higher MN frequencies than those with fewer years (FR = 1.40, 95% CI: 1.10–1.77, P < 0.05). Multivariate Poisson regression analysis showed that those who carried GSTM1 (?) (FR = 1.48, 95% CI: 1.14–1.92) or GSTT1 (?) (FR = 1.42, 95% CI: 1.10–1.83) genotypes, and especially those who carried both (FR = 2.10, 95% CI: 1.43–3.09) exhibited significantly higher MN frequencies than those carrying GSTM1 (+), GSTT1 (+) genotypes or their combination. The GSTP1 Val genotype did not affect MN frequency (P > 0.05). Our results suggested that higher levels of BD exposure in the workplace resulted in increased chromosomal damage, and that polymorphisms in GSTT1 and GSTM1 genes might modulate the genotoxic effects of BD exposure. Furthermore, the GSTT1 and GSTM1 polymorphisms exhibited an additive effect. Finally, urinary DHBMA was found to provide a biomarker that correlated with airborne BD levels.     

Surveillance,Epidemiology, and End Results-based analysis of the impact of preoperative or postoperative radiotherapy on survival outcomes for T3N0 rectal cancer

Purpose: Preoperative chemoradiation has been established as standard of care for T3/T4 node-positive rectal cancer. Recent work, however, has called into question the overall benefit of radiation for tumors with lower risk characteristics, particularly T3N0 rectal cancers. We retrospectively analyzed T3N0 rectal cancer patients and examined how outcomes differed according to the sequence of treatment received. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to analyze T3N0 rectal cancer cases diagnosed between 1998 and 2008. Treatment consisted of surgery alone (No RT), preoperative radiation followed by surgery (Neo-Adjuvant RT), or surgery followed by postoperative radiation (Adjuvant RT). Demographic and tumor characteristics of the three groups were compared using t-tests for the comparison of means. Survival information from the SEER database was utilized to estimate cause-specific survival (CSS) and to generate Kaplan–Meier survival curves. Multivariate analysis (MVA) of features associated with outcomes was conducted using Cox proportional hazards regression models with Adjuvant RT, Neo-Adjuvant RT, No RT, histological grade, tumor size, year of diagnosis, and demographic characteristics as covariates. Results: 10-Year CSS estimates were 66.1% (95% CI 62.3–69.6%; P = 0.02), 73.5% (95% CI 68.9–77.5%; P = 0.02), and 76.1% (95% CI 72.4–79.4%; P = 0.02), for No RT, Neo-Adjuvant RT, and Adjuvant RT, respectively. On MVA, Adjuvant RT (HR = 0.688; 95% CI, 0.578–0.819; P < 0.001) was associated with significantly decreased risk for cancer death. By contrast, Neo-Adjuvant RT was not significantly associated with improved cancer survival (HR = 0.863; 95% CI, 0.715–1.043; P = 0.127). Conclusion: Adjuvant RT was associated with significantly higher CSS when compared with surgery alone, while the benefit of Neo-Adjuvant RT was not significant. This indicates that surgery followed by Adjuvant RT may still be an important treatment plan for T3N0 rectal cancer with potentially significant survival advantages over other treatment sequences.     

STK15 rs2273535 polymorphism and cancer risk: A meta-analysis of 74,896 subjects

Background: It has been suggested that the serine/threonine kinase 15 (STK15) T91A rs2273535 polymorphism is associated with susceptibility to cancer. However, the results are conflicting. We performed this meta-analysis to derive a more precise estimation of the relationship. Methods: PubMed was searched to select studies. Case–control studies containing available genotype frequencies of the STK15 rs2273535 polymorphism were chosen, and the odds ratio (OR) with its 95% confidence interval (CI) was utilized to assess the strength of association. Results: 52 studies – including 34,057 cases and 40,839 controls – were identified. A significant effect of the STK15 rs2273535 polymorphism on cancer risk was found (AA vs. TT: OR = 1.13, 95%CI = 1.01–1.26, P_{heterogeneity} < 0.001; AA vs. TA/TT: OR = 1.12, 95%CI = 1.02–1.22, P_{heterogeneity} < 0.001; TA/AA vs. TT: OR = 1.06, 95%CI = 1.01–1.12, P_{heterogeneity} < 0.001). Stratified analysis by cancer type revealed that the STK rs2273535 polymorphism may contribute to the risk of breast cancer (AA vs. TT: OR = 1.21, 95%CI = 1.01–1.44, P_{heterogeneity} = 0.002), colorectal cancer (AA vs. TA/TT: OR = 1.24, 95%CI = 1.05–1.47, P_{heterogeneity} = 0.124), and esophageal cancer (AA vs. TA/TT: OR = 1.19, 95%CI = 1.02–1.39, P_{heterogeneity} = 0.148). Further subgroup analysis by ethnicity indicated that there was a statistically increased cancer risk in Asians (AA vs. TA/TT: OR = 1.20, 95%CI = 1.05–1.37, P_{heterogeneity} = 0.004). Conclusion: This meta-analysis suggests that the STK15 rs2273535 polymorphism is a candidate gene polymorphism for cancer susceptibility, especially in Asian populations.     

Circulating soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as diagnostic and prognostic marker in neonatal sepsis

ObjectiveTriggering receptor expressed on myeloid cells-1 (TREM-1) is an important receptor involved in the innate inflammatory response and sepsis. We assessed soluble TREM-1 (sTREM-1) in 112 septic neonates (63 culture-positive and 49 culture-negative) and 40 healthy controls as a potential early diagnostic and prognostic marker for neonatal sepsis (NS).MethodsStudied neonates were evaluated for early- or late-onset sepsis using clinical and laboratory indicators upon admission. sTREM-1 was measured on initial sepsis evaluation and at 48 h after antibiotic therapy. For ethical reasons, cord blood samples were collected from control neonates and only samples from neonates that proved to be healthy by clinical examination and laboratory analysis were further analyzed for sTREM-1.ResultsBaseline sTREM-1 levels were significantly elevated in culture-proven (1461.1 ± 523 pg/mL) and culture-negative sepsis (1194 ± 485 pg/mL) compared to controls (162.2 ± 61 pg/mL) with no significant difference between both septic groups. Culture-positive or negative septic preterm neonates had significantly higher sTREM-1 compared to full term neonates. sTREM-1 was significantly higher in neonates with early sepsis than late sepsis and was associated with high mortality. sTREM-1 was significantly decreased 48 h after antibiotic therapy compared to baseline or levels in neonates with persistently positive cultures. sTREM-1 was positively correlated to white blood cells (WBCs), absolute neutrophil count, immature/total neutrophil (I/T) ratio, C-reactive protein (hs-CRP) and sepsis score while negatively correlated to gestational age and weight. hs-CRP and sepsis score were independently related to sTREM-1 in multiregression analysis. sTREM-1 cutoff value of 310 pg/mL could be diagnostic for NS with 100% sensitivity and specificity (AUC, 1.0 and 95% confidence interval [CI], 0.696–1.015) while the cutoff value 1100 pg/mL was predictive of survival with 100% sensitivity and 97% specificity (AUC, 0.978 and 95% CI, 0.853–1.13). However, hs-CRP cutoff 13.5 mg/L could be diagnostic for NS with a sensitivity of 76% and specificity of 72% (AUC, 0.762 and 95% CI, 0.612–0.925) and levels were not related to survival as no significant difference was found between dead and alive septic neonates.ConclusionsElevated sTREM-1 could be considered an early marker for NS that reflects sepsis severity and poor prognosis.     

Diabetes,physical activity and breast cancer among Hispanic women

Purpose: We assessed the association between diabetes and breast cancer and whether physical activity modified the effect of diabetes on breast cancer in Hispanic women. Methods: We used data from a case-control study of breast cancer among Hispanic women aged 30–79 conducted between 2003 and 2008 on the Texas–Mexico border. In-person interviews were completed with 190 incident breast cancer cases ascertained through surgeons and oncologists, and 979 controls who were designated as both high-risk (n = 511) and low-risk (N = 468) for breast cancer (with respective response rates of 97%, 83% and 74%). Results: After adjustment for menopausal status and mammography screening, there was no effect of diabetes on breast cancer risk (high-risk control group odds ratio [OR] 1.02, 95% confidence interval [CI] 0.71–1.48; low-risk control group OR 0.87, 0.58–1.30). Women who had a diabetes history and did not exercise were at no risk of breast cancer (OR 0.96, 95% CI 0.63–1.48) or a slightly reduced breast cancer risk (low-risk control group OR 0.72, 95% CI 0.46–1.15) depending on the control group used, while women with diabetes who did exercise had significantly reduced breast cancer risk (OR 0.41, 95% CI 0.21–0.83) regardless of the control group used (high-risk control group p-value for interaction = 0.013, low-risk control group p-value for interaction 0.183). Conclusions: Should other studies confirm our results, physical activity should be explored as a means of reducing breast cancer risk in diabetic women.     

Delirium prevalence in a Colombian hospital,association with geriatric syndromes and complications during hospitalization

BackgroundThe aim of this paper is to describe the prevalence of Delirium and the factors associated with its presentation and complications identified in a geriatric unit in Colombia.Material and methodsThis is a retrospective observational study that included all patients admitted consecutively for two years in a geriatric unit of a hospital in Bogotá, Colombia. We assessed delirium prevalence with the Confusion Assessment Method (CAM). The independent variables were age, sex, functional impairment (Barthel < 90), malnutrition (MNA < 12), pressure ulcers at admission, state of the social support network, number of comorbidities, polypharmacy (5 or more drugs), complications such as ICU requirement, hospital stay, in-hospital functional impairment and mortality were also evaluated. As an exclusion criterion: not having CAM registered in the medical record, all the patients had this information.ResultsWe studied 1599 subjects with a mean age of 86 years (IQR 9). Delirium prevalence was 51.03%. Delirium was associated with a higher rate of: pressure ulcers on admission [OR 3.76 (CI 2.60–5.43 p < 0.001)], functional impairment [OR 2.38 (CI 1.79–3.16 p < 0.001)], malnutrition [OR 2.06 (CI 1.56–2.73 p < 0.001)], and infection [OR 1.46 (CI 1.17–1.82 p < 0.001)]. Moreover delirium has a higher association with mortality [OR 2.80 (1.03–7.54 p = 0.042)], in-hospital functional decline [OR 1.82 (1.41–2.36 p < 0.001)], and longer hospital stay [OR 1.04 (1.04–1.09 p = 0.006)]; independently of age, sex, pressure ulcers on admission, functional impairment, malnutrition, dementia, infection and limited social network.ConclusionOur study suggests that infectious diseases and geriatric syndromes such as, functional dependence, pressure ulcers, malnutrition or major cognitive impairment are independently associated with the presence of delirium on admission. Additionally, the presence of delirium is independently associated during hospitalization with complications, longer hospital stay, functional impairment and mortality.