Punto de corte de espesor de tejido adiposo epicárdico para predecir síndrome metabólico en población venezolana

ObjectiveTo define an echocardiographically-assessed cut-off point for epicardial adipose tissue (EAT) thickness associated to metabolic syndrome (MS) components in Venezuelan subjects.MethodsFifty-two subjects aged 20-65 years diagnosed with MS according to International Diabetes Federation criteria and 45 sex- and age-matched controls were selected. Blood glucose and plasma lipids were tested; EAT thickness and left ventricular mass were measured by echocardiography.ResultsNo significant age and sex differences were found between the two groups. Body weight, body mass index, waist circumference, and systolic and diastolic blood pressure were significantly higher (P = .0001) in the MS group. This group showed significantly higher levels of fasting blood glucose (P = .0001), total cholesterol (P = .002), LDL-C (P = .007), non-HDL-C (P = .0001), triglycerides (P = .0001), Tg-HDL-C ratio (P = .0001), and lower HDL-C levels (P = .0001) as compared to the control group. EAT thickness (P = .0001) and left ventricular mass (P = .017) were significantly higher in the MS group. The ROC curve showed an AUC of 0.852 (P = .0001) with a power of the test of 0.99. A 5-mm EAT thickness showed a sensitivity of 84.62% (95% CI: 71.9-93.1) and a specificity of 71.11% (95% CI: 55.7-83.6) for predicting MS. The odds ratio of this population for experiencing MS due to an EAT ≥ 5 mm was 8.25 (95% CI: 3.15-21.56; P = .0001).ConclusionAn EAT value ≥ 5 mm has good sensitivity and specificity for predicting MS in the Venezuelan population.     

Colesevelam Hydrochloride to Treat Hypercholesterolemia and Improve Glycemia in Prediabetes: A Randomized,Prospective Study

ObjectiveTo assess the effect of the bile acid sequestrant colesevelam hydrochloride in patients with hypercholesterolemia and prediabetes.MethodsIn this 16-week, randomized, double-blind study, adults with untreated prediabetes (2-hour postoral glucose tolerance test [OGTT] glucose ≥ 140 to 199 mg/dL, fasting plasma glucose [FPG] ≥ 110 to 125 mg/ dL, or both), low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL, and triglycerides < 500 mg/dL were randomly assigned to receive colesevelam (3.75 g/d) or placebo. The primary end point was percent change in LDL-C from baseline to week 16 with last observation carried forward. Secondary end points included change in FPG, hemoglobin A1c (A1C), and 2-hour post-OGTT glucose level from baseline to week 16 and attainment of LDL-C and FPG targets.ResultsIn total, 216 patients were randomized (colesevelam, 108; placebo, 108). In comparison with placebo, colesevelam significantly reduced LDL-C (mean treatment difference, -15.6%), non-high-density lipoprotein cholesterol (-9.1%), total cholesterol (-7.2%), apolipoprotein B (-8.1%) (P < .001 for all the foregoing), FPG (median, -2.0 mg/dL; P = .02), and A1C (mean, -0.10%; P = .02). Colesevelam did not significantly change 2-hour post-OGTT glucose (-1.9 mg/dL; P = .75) or high-density lipoprotein cholesterol (-0.5%; P = .80). In addition, colesevelam significantly increased triglyceride levels relative to placebo (median, 14.3%; P < .001). The proportion of patients achieving target levels with colesevelam versus placebo, respectively, was as follows: LDL-C < 100 mg/dL (29% versus 11%; P < .001), A1C < 6.0% (37% versus 25%; P = .05), FPG < 110 mg/dL (48% versus 56%; P = .97), and normalization of glucose (FPG < 100 mg/dL [40% versus 23%; P = .06]). Colesevelam had a weight-neutral effect and was well tolerated.ConclusionColesevelam is an option for managing the lipid profile and normalizing glucose levels in patients with hypercholesterolemia and prediabetes. Further study is warranted to determine whether colesevelam slows or prevents progression of prediabetes to type 2 diabetes. (Endocr Pract. 2010;16:617-628)     

Association of Glycemic Control Parameters with Clinical Outcomes in Chronic Critical Illness

ObjectiveChronic critical illness (CCI) is a term used to designate patients requiring prolonged mechanical ventilation and tracheostomy with associated poor outcomes. The present study assessed the impact of glycemic parameters on outcomes in a CCI population.MethodsA retrospective case series was performed including 148 patients in The Mount Sinai Hospital Respiratory Care Unit (2009-2010). Utilizing a semi-parametric mixture model, trajectories for the daily mean blood glucose (BG), BG range, and hypoglycemia rate over time identified low- (n = 87) and high-risk (n = 61) hyperglycemia groups and low- (n = 90) and high-risk (n = 58) hypoglycemia groups. The cohort was also classified into diabetes (DM, n = 48), stress hyperglycemia (SH, n = 85), and normal glucose (n = 15) groups.ResultsHospital- (28% vs. 13%, P = .0199) and 1-year mortality (66% vs. 46%, P = .0185) rates were significantly greater in the high- versus low-risk hyperglycemia groups, respectively. The hypoglycemia rate (< 70 mg/dL) was lower among ventilator-liberated patients compared to those who failed to liberate (0.092 vs. 0.130, P < .0001). In the SH group, both hospital mortality (high-risk hyperglycemia 48% and low-risk hyperglycemia 15%, P = .0013) and 1-year mortality (high-risk 74% and low-risk 50%, P = .0482) remained significantly different, while no significant difference in the diabetes group was observed. There were lower hypoglycemia rates with SH compared to diabetes (< 70 mg/dL: 0.086 vs. 0.182, P < .0001; < 40 mg/dL: 0.012 vs. 0.022, P = .0118, respectively).ConclusionTighter glycemic control was associated with improved outcomes in CCI patients with SH but not in CCI patients with diabetes. Confirmation of these findings may lead to stratified glycemic control protocols in CCI patients based on the presence or absence of diabetes. (Endocr Pract. 2014;20:884-893)     

Initial Combination Therapy with Metformin and Colesevelam for Achievement of Glycemic and Lipid Goals Min Early Type 2 Diabetes

ObjectiveTo evaluate the efficacy and safety of initial combination therapy with metformin plus colesevelam in patients with early type 2 diabetes.MethodsIn this 16-week, randomized, double-blind, placebo-controlled study, adults with type 2 diabetes (hemoglobin A1c [A1C] values of 6.5% to 10.0%) and hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C] levels ≥ 100 mg/dL) were randomly assigned (1:1) to colesevelam (3.75 g/d) or placebo in combination with open-label metformin (850 mg/d; uptitrated at week 2 to 1, 700 mg/d). The primary efficacy evaluation was change in A1C from baseline to study end (week 16 with last observation carried forward).ResultsIn total, 286 patients were randomized: metformin/colesevelam (n = 145) or metformin/placebo (n = 141). Mean A1C was reduced by 1.1% with metformin/ colesevelam (from 7.8% at baseline to 6.6% at study end) and by 0.8% with metformin/placebo (from 7.5% to 6.7%), resulting in a treatment difference of -0.3% at study end (P = .0035). In addition, metformin/colesevelam significantly reduced LDL-C (-16.3%), total cholesterol (-6.1%), non-high-density lipoprotein cholesterol (-8.3%), apolipoprotein B (-8.0%), and high-sensitivity C-reactive protein (-17%) and increased apolipoprotein A-I (+ 4.4%) and triglycerides (+ 18.6%) versus metformin/placebo (P < .01 for all). The proportions of patients who achieved recommended goals with metformin/colesevelam versus metformin/placebo, respectively, were as follows: A1C < 7.0% (67% versus 56% [P = .0092]), LDL-C < 100 mg/dL (48% versus 18% [P < .0001]), and composite A1C < 7.0% + LDL-C < 100 mg/dL (40% versus 12% [P < .0001]). Safety and tolerability were similar between the treatment groups.ConclusionMetformin plus colesevelam may be a valid option for initial therapy to achieve glycemic and lipid goals safely in early type 2 diabetes. (Endocr Pract. 2010;16:629-640)     

Clinical Markers Implying the Need for Treatment in Women with Gestational Diabetes Mellitus

ObjectiveTo assess the association of the point-of-care hemoglobin A_1c (POC A1C), fasting blood glucose (FBG), and BMI with fetal macrosomia and the need for medication in women with gestational diabetes (GDM).MethodsPOC A1C, FBG, and BMI values at GDM diagnosis and fetal weight at delivery were obtained for women identified from a prospective patient registry. These outcomes were compared between women who did not require medication for GDM and women who did require medication.ResultsMean values of POC A1C, FBG, and BMI in 67 patients who required medication were higher than those in 71 patients who did not require medication (POC A1C: 5.72 ± 0.45% vs 5.35 ± 0.46% [P < .001]; FBG: 97.4 ± 12.3 mg/dL vs 86.4 ± 9.5 mg/dL [P < .001]; BMI: 35.4 ± 6.4 kg/m2 vs 30.4 ± 6.2 kg/m2 [P < .001]). There was a modest correlation between POC A1C and FBG (Spearman rho 0.4, P < .001) and between POC A1C and BMI (Spearman rho 0.366, P < .001). Maternal POC A1C was not correlated with fetal weight at delivery (Spearman rho –0.010, P = .915).ConclusionsHigher POC A1C, FBG, and BMI values were associated with the need for medication in women with GDM. The use of clinical markers to assess glycemic control sooner in pregnancy may lead to the earlier identification of women at risk for GDM and earlier intervention to decrease the risk for complications. (Endocr Pract. 2012;18:62-65)     

Preadmission Glycemic Control and Changes to Diabetes Mellitus Treatment Regimen After Hospitalization

ObjectiveTo evaluate treatment patterns associated with diabetes medication regimen changes after hospitalization on the basis on preadmission hemoglobin A_1c levels.MethodsIn this retrospective database analysis, patients with a diabetes diagnosis, hospitalization, and documented hemoglobin A_1c level within the 90 days leading up to hospital admission were identified in an administrative claims database. Treatment regimens were assessed before and after hospitalization. The proportion of patients who had progression, reduction, or no change in therapy was compared across hemoglobin A_1c subgroups: hemoglobin A_1c < 7.0%, hemoglobin A_1c 7.0%-7.9%, and hemoglobin A_1c ≥ 8.0%.ResultsFour hundred patients were included (192 in hemoglobin A_1c < 7.0% group, 94 in hemoglobin A_1c 7.0% 7.9% group, and 114 in hemoglobin A_1c ≥ 8.0% group). Demographically, hemoglobin A_1c subgroups did not differ significantly (mean age, 57 years; 47.5% male). With respect to therapeutic regimen overall, 28%, 24%, and 48% of patients experienced progression, reduction, and no change, respectively. Across hemoglobin A_1c subgroups, 37.7% of patients in the hemoglobin A_1c ≥ 8.0% subgroup had therapy progression compared with 26% and 20.2% in the hemoglobin A_1c < 7.0% and hemoglobin A_1c 7.0%-7.9% subgroups, respectively (P = .032 and P = .006, respectively). Within the progression category, progression via insulin initiation was significantly higher in the hemoglobin A_1c ≥ 8.0% subgroup (55.8%) than in the hemoglobin A_1c < 7.0% subgroup (16%, P < .001), but not significantly higher than in the hemoglobin A_1c 7.0%-7.9% subgroup (36.8%, P = .084). In the hemoglobin A_1c ≥ 8.0% subgroup, a lower percentage of patients, 35.1%, experienced no therapy change than in both the hemoglobin A_1c < 7.0% subgroup (52.6%) and the hemoglobin A_1c 7.0%-7.9% subgroup (54.3%) (P = .003 and P = .006, respectively). There was no difference between subgroups in reduction of therapy.ConclusionsA higher proportion of patients with a hemoglobin A_1c level ≥ 8.0% had progression of their antidiabetes therapy after hospitalization and fewer patients had no change in therapy than those in lower hemoglobin A_1c subgroups. These data suggest that clinicians may be using hemoglobin A_1c measurements to guide discharge planning treatment decisions. (Endocr Pract. 2012;18:371-375)     

Baseline and 1-year follow-up differences between hip-fracture patients admitted from nursing homes and the community. A cohort study on 509 consecutive patients (FONDA Cohort)

ObjectiveTo determine the clinical and functional differences at hospital admission and at 1 year after a hip fracture (HF) in nursing homes (NH) and community-dwelling (CD) patients.MethodsAll patients with HF admitted to the orthogeriatric unit at a university hospital between January 2013 and February 2014 were prospectively included. Clinical and functional variables, and mortality were recorded during the hospital admission. The patients were contacted by telephone at 1 year to determine their vital condition and functional status.ResultsA total of 509 patients were included, 116 (22.8%) of whom came from NH. Compared with the CD patients, the NH patients had higher surgical risk (ASA ≥3: 83.6% vs. 66.4%, P < .001), poorer theoretical vital prognosis (Nottingham Profile ≥5: 98.3% vs. 56.6%, P< .001), higher rate of previous functional status (median Barthel index: 55 [IQR, 36-80] vs. 90 [IQR, 75-100], P< .001), poorer mental status (Pfeiffer's SPMSQ >2: 74.1% vs. 40.2%, P< .001), and a higher rate of sarcopenia (24.3% vs. 15.2%, P< .05). There were no differences in in-hospital or at 1-year mortality. At 1 year, NH patients recovered their previous walking capacity at a lower rate (38.5% vs. 56.2%, P< .001).ConclusionsAmong the patients with HF treated in an orthogeriatric unit, NH patients had higher, surgical risk, functional and mental impairment, and a higher rate of sarcopenia than CD patients. At 1 year of follow-up, NH patients did not have higher mortality, but they recovered their previous capacity for walking less frequently.     

Effect of Hospital Admission on Glycemic Control 1 Year After Discharge

ObjectiveTo assess the effect of hospital admission on glycemic control in patients with diabetes up to 1 year after discharge.MethodsWe retrospectively studied 826 adults with diabetes admitted to a tertiary care medical center and with available hemoglobin A_1c (A1C) values for 6 months before admission and 1 year after discharge. We compared them with 826 nonhospitalized adults with diabetes matched for age, sex, race, comorbidity, and baseline A1C level. We determined the change in A1C value relative to hospitalization and baseline A1C level by using multivariate random effects models for repeated measures. Logistic regression analysis was performed to determine predictors of achieving recommended A1C levels at 1 year.ResultsPatients with baseline A1C levels ≥ 9% had an adjusted rate of change in A1C value of − 0.10% per month (95% confidence interval [CI], − 0.18 to − 0.022; P = .012) during the course of 1 year, without significant differences between hospitalized and nonhospitalized patients in the mean rate of change. Hospitalized patients, however, were less likely to achieve an A1C goal of ≤ 7% at 1 year (odds ratio, 0.68; 95% CI, 0.55 to 0.86; P < .001) or an A1C of < 8% at 1 year (odds ratio, 0.62; 95% CI, 0.48 to 0.81; P < .001) in comparison with the nonhospitalized patients.ConclusionDespite an overall trend toward improved glycemia over time, hospitalized patients with uncontrolled diabetes were less likely to achieve glycemic targets at 1 year in comparison with matched nonhospitalized patients. These results suggest a missed opportunity to improve long-term glycemic control in hospitalized patients with diabetes. (Endocr Pract. 2012;18:456-463)     

Hemoglobin A1C,Mean Glucose,and Persistence of Glycation Ratios in Insulin-Treated Diabetes

ObjectiveDetermine the relationship between mean glucose (MG), as assessed by continuous glucose monitoring (CGM), and hemoglobin A_1c (A1C) in insulin-requiring adults in a clinical practice setting and examine the persistence of this relationship over time.MethodsIn this retrospective record review in a diabetes practice, a linear regression model was developed using data sets from all patients with ≥ 1 available download of a Dexcom SevenPlus CGM device in which there was > 50% utilization in the 60 days prior to a laboratory A1C. Persistence of the MG to A1C relationship was examined in patients with ≥ 2 data sets available.ResultsA total of 139 patients had ≥ 1 data set available for evaluation, and 101 patients had ≥ 2 data sets (range, 2 to 6; total, 279). The slope of the MG versus A1C curve was 19.5 mg/dL for each 1% change in A1C, with an intercept of 17.7 mg/dL. Although 88% of the measured MG values were within 15% of the A1C-predicted MG, there was substantial variation in individuals, with differences as large as ± 26%. The MG to A1C (MG:A1C) ratio, which is a measure of glycation, was normally distributed, with a median of 21.6. Spearman correlation coefficients for the MG:A1C ratio on repeated measures ranged from 0.52 to 0.73, demonstrating persistence.ConclusionThe relationship between MG and A1C is linear in a population but can vary between individuals. The MG:A1C ratio was normally distributed, tended to persist in individuals over time, and thus could be useful to identify apparent high and low glycators. Glycemic goals may need to be modified in such patients. (Endocr Pract. 2014;20:252-260)     

Obstructive Sleep Apnea Predisposes to Nonalcoholic Fatty Liver Disease in Patients with Polycystic Ovary Syndrome

ObjectiveSome studies have shown a higher prevalence of nonalcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA) in patients with polycystic ovary syndrome (PCOS). The objective of this study was to assess NAFLD in PCOS women with and without OSA. A possible role of high serum androgen levels in the development of OSA in PCOS women was also investigated.MethodsBiochemical, hormonal, and polysomnography parameters were determined in 38 premenopausal PCOS patients. NAFLD was evaluated by ultrasound. Testosterone was measured by an immunoassay.ResultsSerum androgen levels and the prevalence of NAFLD (83.3% vs. 26.9%; P < .001) were higher in patients with OSA than those without OSA. The mean apnea-hypopnea index (AHI) was higher in patients with NAFLD than in those without NAFLD (16.87 events [ev]/h vs. 1.57 ev/h; P < .002). On multivariate logistic regression, where body mass index ≥ 30 kg/m², homeostasis model assessment for insulin resistance ≥ 2.7, and OSA (AHI ≥ 5 ev/h) were independent variables, only OSA was an independent predictor of NAFLD (odds ratio [OR], 7.63; P = .044). Free testosterone levels ≥ 1.07 ng/dL were also independently associated with OSA (OR, 8.18; P = .023).ConclusionIn PCOS women, the occurrence of OSA strongly predisposes them to development of NAFLD and a worse metabolic profile; hence, treatment of OSA might be beneficial for NAFLD. (Endocr Pract. 2014;20:244-251)     

Methylenetetrahydrofolate reductase gene polymorphisms contribute to acute myeloid leukemia and chronic myeloid leukemia susceptibilities: Evidence from meta-analyses

PurposeThe expression of methylenetetrahydrofolate reductase (MTHFR) is associated with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Most studies have linked the common functional C677T and A1298C polymorphisms of the MTHFR gene and susceptibility to AML and CML, but the results were not consistent. The aim of the present study was to derive a more precise estimation of the relationship.MethodsMeta-analyses assessing the association of MTHFR C677T and A1298C variations with AML and CML were conducted. Eligible articles were identified from the PubMed and EMBASE databases. All statistical analyses were conducted using Review Manager Software.Results10 and 10 studies were included in the meta-analysis about the role of C677T polymorphism on the AML and CML risks, respectively; 6 and 4 studies were included about the role of A1298C polymorphism on the AML and CML risks, respectively. Overall, both the C677T and A1298C polymorphisms were significantly associated with CML risk under the recessive model (P = 0.04, OR = 1.35, 95% CI = 1.02–1.79 for C677T and P = 0.003, OR = 2.17, 95% CI = 1.29–3.63 for A1298C). In addition, the risk of CML was higher in 1298CC genotype carriers than in 1298AA genotype carriers (P = 0.004, OR = 2.17, 95% = 1.28–3.69). Conversely, the overall data failed to indicate a significant association of C677T or A1298C polymorphisms with AML risk under any model.ConclusionsThe findings provide evidence that C677T and A1298C polymorphisms are risk factors for CML risk.     

Distribution of Capillary Glycated Hemoglobin Among Adolescents of High School Age

ObjectiveTo report the distribution of glycated hemoglobin (hemoglobin A1c or A1C) in whole blood collected from a cohort of high school students with use of a capillary method.MethodsStudents were recruited from the Diabetes Risk Factor Screening Study conducted in Santa Barbara, California, high schools. Height and weight were measured on portable equipment. Blood was collected by finger stick and analyzed immediately for A1C on the DCA 2000 + analyzer. Students also completed a brief survey that included specification of race or ethnicity and family history of diabetes.ResultsBetween the years 2001 and 2005, A1C was measured in 2,640 14-to 18-year-old high school students. The mean A1C was 4.91%, SE was 0.01%, and range was from 3.5% to 8.5%, including 2 outliers. Both of these students were found to have previously unrecognized type 2 diabetes mellitus. Male subjects had an A1C that was slightly but significantly higher than that in female subjects (difference = 0.05%; P < .001), subjects with a family history of diabetes in a first-degree relative had higher A1C values than those without such a family history (difference = 0.10%; P = .001), and subjects with a body mass index ≥ 95% had higher A1C values than did those with a lower body mass index (difference = 0.011%; P < .001). Non-Hispanic white students had A1C concentrations that were significantly lower than those of African American or Latino students. Age had little effect on the A1C.ConclusionThe A1C distribution in the total study population in this survey was identical to the distribution reported previously with use of the high-performance liquid chromatographic method. This survey establishes standards for capillary A1C in high school students from several racial or ethnic groups. (Endocr Pract. 2008;14:529-534)     

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.     

Anthropometric features and cutaneous melanoma risk: A prospective cohort study in French women

BackgroundEpidemiological studies on anthropometric features and cutaneous melanoma risk in women yielded inconsistent results, with few analyses involving prospective cohort data. Our objective was to explore several anthropometric characteristics in relation to the risk of melanoma in women.MethodsWe prospectively analysed data from E3N, a French cohort involving 98,995 women born in 1925–1950. Participants completed self-administered questionnaires sent biennially over 1990–2008. Relative risks (RRs) and 95% confidence intervals (CIs) were computed using Cox proportional hazards regression models, adjusted for age, number of naevi, freckling, skin and hair colour, skin sensitivity to sun exposure, residential sun exposure, and physical activity.ResultsHeight was positively associated with melanoma in age-adjusted models only (RR = 1.27, 95% CI = 1.05–1.55 for ≥164 cm vs. <160 cm; P for trend = 0.02). After full adjustment, there was a significantly positive relationship between sitting-to-standing height ratio and melanoma risk (RR = 1.40, 95% CI = 1.06–1.86 for ≥0.533 vs. <0.518; P for trend = 0.02). A large body shape at menarche was inversely associated with the risk of melanoma (RR = 0.78, 95% CI = 0.62–0.98; compared with lean). However, weight, body mass index, body surface area, waist or hip circumference, sitting height or leg length were not significantly associated with risk.ConclusionThese results suggest that height, sitting-to-standing height ratio and body shape at menarche may be associated with melanoma risk. Further research is required to confirm these relationships and better understand the underlying mechanisms.     

Regional variations in age at diagnosis and overall survival among patients with chronic myeloid leukemia from low and middle income countries

IntroductionThe epidemiology of chronic myeloid leukemia (CML) in low and middle income countries is limited. As a result, we analyzed a contemporary cohort of patients from low and middle income countries treated with Imatinib through The Glivec^® International Patient Assistance Program (GIPAP).MethodsGeneralized estimating equations (GEE) and Kaplan–Meier estimation were utilized to test for regional variations in age at diagnosis and overall survival among 33,985 patients from 94 countries.ResultsPatients participated from Asia (79.2%), Africa (9.4%), Latin America (8.7%) and Southern/Eastern Europe (2.5%). Sixty-one (61.2%) percent were male. Mean age at diagnosis was 38.5 years (9.4% <20 years and only 4.7% ≥65 years). Using GEE, Asians were youngest (38.3 years), followed by Africans (39.5 years), Southern/Eastern Europeans (41.1 years) and Latin Americans (41.3 years; p < 0.0001). Diagnoses were predominately in chronic stage (78.3%). In 2002, 85.2% of patients had a delay in treatment >1 year; decreasing to 15.5% in 2010 (p < 0.0001). The 3-year overall survival probability was 89.4% (95% CI, 88.9–89.9). In multivariate analysis, risk of death increased among patients 65 years or older at diagnosis (p < 0.0001), time from diagnosis to treatment >1-year (p < 0.0001), diagnoses in the accelerated or blast crisis (p < 0.0001), initial dose of Imatinib >400 mg (p < 0.0001) and among Latin Americans and Africans (p < 0.0001).ConclusionThe GIPAP cohort is the largest series of patients with CML described from low and middle income countries. Differences in age at diagnosis and overall survival exist within and between regions. Additional epidemiological studies should be conducted to assess for possible environmental factors associated with the earlier age at onset.     

Postpartum ovarian activity of Santa Inês lactating ewes fed diets containing soybean hulls as a replacement for coastcross (Cynodon sp.) hay

The Santa Inês, a Brazilian hair sheep, has a non-seasonal breeding activity. Data regarding the duration of the postpartum anestrous period in Santa Inês lactating ewes is lacking and the objective of this trial was to determine the effects of replacing neutral detergent fibre (NDF) provided by coastcross (Cynodon sp.) hay with NDF contained in soybean hulls (SH) on the postpartum ovarian activity—as measured by the serum progesterone (P₄) concentration. Fifty-six lactating ewes (body weight 56.1 ± 6.8 kg) were individually penned and used in a randomized complete block design with 14 blocks and four treatments. The SH NDF replaced 33 (SH33), 67 (SH67), or 100% (SH100) of the NDF contributed by coastcross hay in the control diet (SH0). This resulted in a SH inclusion at rates of 0, 25, 54, and 85% of the dietary dry matter (DM). Blood samples were collected twice weekly from the 14th to 84th day postpartum and the serum P₄ concentrations determined by radioimmunoassay (RIA). It was estimated that the 1st postpartum ovulation occurred 6 days before the date that a serum P₄ ≥ 1 ng/ml concentration was first recorded. The mean body condition score (BCS; 0–5 scale) was 3.0 ± 0.19 on day 14 postpartum and the mean BCS at day 56 postpartum increased linearly (P < 0.01) with the inclusion levels of SH (3.09, 3.24, 3.34, and 3.36, respectively). Treatments did not differ significantly in the induction of postpartum days to the resumption of ovarian luteal activity (34.1 ± 15.3 days postpartum). On days 25, 50, and 75 postpartum 36, 80, and 100% of the ewes had resumed ovarian activity, respectively. Non-esterified fatty acid concentration decreased quadratically (P < 0.05) with the SH inclusion, with values of 0.323, 0.244, 0.204, and 0.216 mequiv./l for the SH0, SH33, SH67, and SH100 treatments being recorded, respectively. Replacement of the NDF provided by coastcross hay with the NDF from the SH did not influence the duration of the postpartum anestrous period in Santa Inês lactating ewes. Considering a 150-day gestation period and the 34 days postpartum anestrous demonstrated in the present study, the current production system of a lambing interval of 8 months (3 lambing events in 2 years) may not be optimizing the production potential and a system in which the lambing interval is shortened by at least 1 month may be feasible.     

Effect of hENT1 polymorphism G-706C on clinical outcomes of gemcitabine-containing chemotherapy for Chinese non-small-cell lung cancer patients

AimTo identify the single-nucleotide polymorphism (SNP) of hENT1 G-706C that is associated with response to gemcitabine-containing chemotherapy, and to determine the prognosis in patients with non-small-cell lung cancer (NSCLC).MethodsPatients with stage III (A + B) or IV NSCLC were recruited for this study (n = 225). Each subject received gemcitabine-containing chemotherapy. The association between human equilibrative nucleoside transporter 1 (hENT1) polymorphism G-706C (rs61758845) and therapeutic effect was evaluated. The SNP hENT1 G-706C was genotyped by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) assays.ResultsThe polymorphic genotype and the allele frequency of hENT1 G-706C was significantly different between chemotherapy responders and non-responders; to be specific, the response rate of patients carrying an hENT1-706 GG allele was higher than that of patients with a GC or CC genotype. Logistic regression analysis showed that having the GC or CC genotypes was associated with a higher risk of being a non-responder compared with having the GG genotype (OR = 2.34, 95% CI: 1.14–4.80; P = 0.02). The overall survival in patients with the GG genotype was significantly longer than in those with GC or CC genotype (19.0 versus 15.1 months, P < 0.001). The hazard ratio for the (GC + CC) genotype was 1.89 (95% CI: 1.23–2.90) compared with GG carriers (P = 0.004).ConclusionsThe hENT1 genetic polymorphism of hENT1 G-706C was associated with response to the gemcitabine-containing chemotherapy and prognosis of NSCLC. Moreover, assaying this SNP in blood cells may represent a valuable biomarker for individualized treatment for NSCLC patients.     

Expression of the Androgen Receptor,pAkt, and pPTEN in Breast Cancer and Their Potential in Prognostication

BACKGROUNDImportance of androgen receptor (AR) as an independent prognostic marker in Pakistani women with breast cancer (BCa) remains unexplored. Our aim was to identify the expression and potential prognostic value of AR, its upstream regulator (pAkt) and target gene (pPTEN) in invasive BCa.METHODSThis study used a cohort of 200 Pakistani women with invasive BCa diagnosed during 2002-2011. Expression of AR, pAkt and pPTEN was determined on formalin fixed paraffin embedded tissue sections by immunohistochemistry. The association of AR, pAkt and pPTEN with clinicopathological parameters was determined. Survival analyses were undertaken on patients with ≥ 5 years of follow-up (n = 82).RESULTSExpression of AR, pAkt and pPTEN was observed in 47.5%, 81.3% and 50.6% of patients, respectively. AR-expressing tumors were low or intermediate in grade (P < .001) and expressed ER (P = .002) and PR (P = .001). Patients with AR⁺ tumors had significantly higher OS (Mean OS = 10.2 ± 0.465 years) compared to patients with AR^? tumors (Mean OS = 5.8 ± 0.348 years) (P = .047). Furthermore, AR-positivity was associated with improved OS in patients receiving endocrine therapy (P = .020). Patients with AR⁺ /pAkt⁺ /pPTEN^? tumors, had increased OS (Mean OS = 7.1 ± 0.535 years) compared to patients with AR^?/pAkt⁺/pPTEN^? tumors (Mean OS = 5.1 ± 0.738 years).CONCLUSIONAR-expressing tumors are frequently characterized by low or intermediate grade tumors, expressing ER and PR. In addition, expression of AR, pAkt and pPTEN, could be considered in prognostication of patients with invasive BCa.