Diagnostic and Prognostic Impact of Circulating YKL-40, IL-6, and CA 19.9 in Patients with Pancreatic Cancer

Purpose

We tested the hypothesis that high plasma YKL-40 and IL-6 associate with pancreatic cancer and short overall survival.

Patients and Methods

In all, 559 patients with pancreatic cancer from prospective biomarker studies from Denmark (n = 448) and Germany (n = 111) were studied. Plasma YKL-40 and IL-6 were determined by ELISAs and serum CA 19.9 by chemiluminescent immunometric assay.

Results

Odds ratios (ORs) for prediction of pancreatic cancer were significant for all biomarkers, with CA 19.9 having the highest AUC (CA 19.9: OR = 2.28, 95% CI 1.97 to 2.68, p<0.0001, AUC = 0.94; YKL-40: OR = 4.50, 3.99 to 5.08, p<0.0001, AUC = 0.87; IL-6: OR = 3.68, 3.08 to 4.44, p<0.0001, AUC = 0.87). Multivariate Cox analysis (YKL-40, IL-6, CA 19.9, age, stage, gender) in patients operated on showed that high preoperative IL-6 and CA 19.9 (dichotomized according to normal values) were independently associated with short overall survival (CA 19.9: HR = 2.51, 1.22–5.15, p = 0.013; IL-6: HR = 2.03, 1.11 to 3.70, p = 0.021). Multivariate Cox analysis of non-operable patients (Stage IIB-IV) showed that high pre-treatment levels of each biomarker were independently associated with short overall survival (YKL-40: HR = 1.30, 1.03 to 1.64, p = 0.029; IL-6: HR = 1.71, 1.33 to 2.20, p<0.0001; CA 19.9: HR = 1.54, 1.06 to 2.24, p = 0.022). Patients with preoperative elevation of both IL-6 and CA 19.9 had shorter overall survival (p<0.005) compared to patients with normal levels of both biomarkers (45% vs. 92% alive after 12 months).

Conclusions

Plasma YKL-40 and IL-6 had less diagnostic impact than CA 19.9. Combination of pretreatment YKL-40, IL-6, and CA 19.9 may have clinical value to identify pancreatic cancer patients with the poorest prognosis.     

Association between Milk and Milk Product Consumption and Anthropometric Measures in Adult Men and Women in India: A Cross-Sectional Study

Background

The nutritional aetiology of obesity remains unclear, especially with regard to the role of dairy products in developing countries.

Objective

To examine whether milk/milk product consumption is associated with obesity and high waist circumference among adult Indians.

Methods

Information on plain milk, tea, curd and buttermilk/lassi consumption assessed using a Food Frequency Questionnaire was obtained from the cross-sectional sib-pair designed Indian Migration Study (3698 men and 2659 women), conducted at four factory locations across north, central and south India. The anthropometric measures included were Body Mass Index (BMI) and Waist Circumference (WC). Mixed-effect logistic regression models were conducted to accommodate sib-pair design and adjust for potential confounders.

Results

After controlling for potential confounders, the risk of being obese (BMI≥25 kg/m²) was lower among women (OR = 0.57;95%CI:0.43−0.76;p≤0.0001) and men (OR = 0.67;95%CI: 0.51−0.87;p = 0.005), and the risk of a high WC (men: >90 cm; women: >80 cm) was lower among men (OR = 0.71;95%CI:0.54−0.93;p = 0.005) and women (OR = 0.79;95%CI:0.59−1.05;p>0.05) who consume ≥1 portions of plain milk daily than those who do not consume any milk. The inverse association between daily plain milk consumption and obesity was also confirmed in sibling-pair analyses. Daily tea consumption of ≥1 portion was associated with obesity (OR = 1.51;95%CI:1.00−2.25;p>0.050) and high WC (OR = 1.65;95%CI:1.08−2.51;p>0.019) among men but not among women but there was no strong evidence of association of curd and buttermilk/lassi consumption with obesity and high waist circumference among both men and women.

Conclusions

The independent, inverse association of daily plain milk consumption with the risk of being obese suggests that high plain milk intake may lower the risk of obesity in adult Indians. However, this is an observational finding and uncontrolled confounding cannot be excluded as an explanation for the association. Therefore, confirmatory studies are needed to clarify this relationship.     

Evaluation of Finnish Diabetes Risk Score in Screening Undiagnosed Diabetes and Prediabetes among U.S. Adults by Gender and Race: NHANES 1999-2010

Objective

To evaluate the performance of Finnish Diabetes Risk Score (FINDRISC) in detecting undiagnosed diabetes and prediabetes among U.S. adults by gender and race.

Methods

This cross-sectional analysis included participants (aged ≥20 years) from the National Health and Nutrition Examination Survey (NHANES) 1999–2010. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve and the optimal cutoff points for identifying undiagnosed diabetes and prediabetes were calculated for FINDRISC by gender and race/ethnicity.

Results

Among the 20,633 adults (≥20 years), 49.8% were women and 53.0% were non-Hispanic White. The prevalence of undiagnosed diabetes and prediabetes was 4.1% and 35.6%, respectively. FINDRISC was positively associated with the prevalence of diabetes (OR = 1.48 for 1 unit increase, p<0.001) and prediabetes (OR = 1.15 for 1 unit increase, p<0.001). The area under ROC for detecting undiagnosed diabetes was 0.75 for total population, 0.74 for men and 0.78 for women (p = 0.04); 0.76 for White, 0.76 for Black and 0.72 for Hispanics (p = 0.03 for White vs. Hispanics). The area under ROC for detecting prediabetes was 0.67 for total population, 0.66 for men and 0.70 for women (p<0.001); 0.68 for White, 0.67 for Black and 0.65 for Hispanics (p<0.001 for White vs. Hispanics). The optimal cutoff point was 10 (sensitivity = 0.75) for men and 12 (sensitivity = 0.72) for women for detecting undiagnosed diabetes; 9 (sensitivity = 0.61) for men and 10 (sensitivity = 0.69) for women for detecting prediabetes.

Conclusions

FINDRISC is a simple and non-invasive screening tool to identify individuals at high risk for diabetes in the U.S. adults.     

Association of Serum 25-Hydroxyvitamin D with Lifestyle Factors and Metabolic and Cardiovascular Disease Markers: Population-Based Cross-Sectional Study (FIN-D2D)

Objectives

Low serum 25-hydroxyvitamin D (25OHD) level has been associated with an increased risk of several chronic diseases. Our aim was to determine lifestyle and clinical factors that are associated with 25OHD level and to investigate connection of 25OHD level with metabolic and cardiovascular disease markers.

Design

In total, 2868 Finnish men and women aged 45–74 years participated in FIN-D2D population-based health survey in 2007. Participants that had a serum sample available (98.4%; n = 2822) were included in this study. 25OHD was measured with chemiluminescent microparticle immunoassay method.

Results

The mean 25OHD level was 58.2 nmol/l in men (n = 1348) and 57.1 nmol/l in women (n = 1474). Mean 25OHD level was lower in the younger age groups than in the older ones (p<0.0001 both in men and women). This study confirmed that low physical activity (p<0.0001 both in men and women), smoking (p = 0.0002 in men and p = 0.03 in women) and high BMI (p<0.0001 in women) are factors that independently associate with low 25OHD level. Of the metabolic and cardiovascular disease markers high triglyceride concentration (p = 0.02 in men and p = 0.001 in women) and high apolipoprotein B/apolipoprotein A1 ratio (p = 0.04 in men and p = 0.03 in women) were independently associated with low 25OHD level.

Conclusions

Higher age did not predict lower 25OHD level in this study population of aged 45–74 years which may derive from a healthy life-style of “active pensioners”. Low physical activity and smoking came up as independent lifestyle factors associated with low 25OHD level. Defining the molecular mechanisms behind the associations of 25OHD with low physical activity and smoking are important objective in future studies. The association of 25OHD with BMI, high triglyceride concentration and apolipoprotein B/apolipoprotein A1 ratio may be related to the role of vitamin D in inflammation, but more detailed studies are needed.     

Disparities in Outcomes following Admission for Cholangitis

Introduction

Few have examined determinants of adverse outcomes in patients presenting with ascending cholangitis. The objective of this study was to examine factors associated with in-hospital mortality, prolonged length of stay (LOS) and increased hospital charges (HC) in patients presenting with acute cholangitis.

Methods

Within the Health Care Utilization Project Nationwide Inpatient Sample (NIS), we focused on patients, 18 years and older, admitted to the emergency department with cholangitis as primary diagnosis (1998–2009). Models were fitted to predict likelihood of in-hospital mortality, prolonged LOS and increased HC. Covariates included race, day of admission, insurance status, socio-economical status and other patient and hospital characteristics.

Results

Overall, weighted estimates of 248,942 patients were admitted with acute cholangitis between 1998 and 2009, of which 13,534 (5.4%) died during the admission. Multivariable analyses revealed that relative to Caucasian patients, African American, Hispanic and Asian and Pacific Islander patients were more likely to die (OR = 1.61, p<0.001, OR = 1.20, p = 0.01 and OR = 1.26, p = 0.008), to experience a prolonged LOS (OR = 1.77, p<0.001, OR = 1.30, p<0.001, 1.34, p<0.001), and to incur high HC (OR = 1.83, p<0.001, OR = 1.51, p<0.001, OR = 1.56, p<0.001). Moreover, Medicaid and Medicare patients were more likely to die (OR = 1.64, p<0.001, OR = 1.24, p<0.001), to experience a prolonged LOS (1.74, p<0.001, OR = 1.25, p<0.001) and to incur high HC (OR = 1.23, p = 0.002, OR = 1.12, p = 0.002) compared to privately insured patients. In subgroup analysis, there were no differences for Medicare patients age 65 years and over. However, those under 65, most of whom have disability or end stage renal disease, were more likely to experience the negative outcomes.

Conclusion

Race and insurance status represent independent predictors of in-hospital mortality and adverse outcomes in patients presenting with cholangitis. Whether these disparities are due to biological predisposition or unequal quality of care requires further investigation. Regardless, efforts should be made to reduce these outcome disparities.     

Measurement of Visceral Fat: Should We Include Retroperitoneal Fat?

Objective

Whether retroperitoneal fat should be included in the measurement of visceral fat remains controversial. We compared the relationships of fat areas in peritoneal, retroperitoneal, and subcutaneous compartments to metabolic syndrome, adipokines, and incident hypertension and diabetes.

Methods

We enrolled 432 adult participants (153 men and 279 women) in a community-based cohort study. Computed tomography at the umbilicus level was used to measure the fat areas.

Results

Retroperitoneal fat correlated significantly with metabolic syndrome (adjusted odds ratio (OR), 5.651, p<0.05) and the number of metabolic abnormalities (p<0.05). Retroperitoneal fat area was significantly associated with blood pressure, plasma glycemic indices, lipid profile, C-reactive protein, adiponectin (r = −0.244, P<0.05), and leptin (r = 0.323, p<0.05), but not plasma renin or aldosterone concentrations. During the 2.94±0.84 years of follow-up, 32 participants developed incident hypertension. Retroperitoneal fat area (hazard ration (HR) 1.62, p = 0.003) and peritoneal fat area (HR 1.62, p = 0.009), but not subcutaneous fat area (p = 0.14) were associated with incident hypertension. Neither retroperitoneal fat area, peritoneal fat area, nor subcutaneous fat areas was associated with incident diabetes after adjustment.

Conclusions

Retroperitoneal fat is similar to peritoneal fat, but differs from subcutaneous fat, in terms of its relationship with metabolic syndrome and incident hypertension. Retroperitoneal fat area should be included in the measurement of visceral fat for cardio-metabolic studies in human.     

Effects of Age,Gender, BMI,and Anatomical Site on Skin Thickness in Children and Adults with Diabetes

Objective

We aimed to assess the effects of age, sex, body mass index (BMI), and anatomical site on skin thickness in children and adults with diabetes.

Methods

We studied 103 otherwise healthy children and adolescents with type 1 diabetes aged 5–19 years, and 140 adults with type 1 and type 2 diabetes aged 20–85 years. The thicknesses of both the dermis and subcutis were assessed using ultrasound with a linear array transducer, on abdominal and thigh skin.

Results

There was an age-related thickening of both dermis (p<0.0001) and subcutis (p = 0.013) in children and adolescents. Girls displayed a substantial pubertal increase in subcutis of the thigh (+54%; p = 0.048) and abdomen (+68%; p = 0.009). Adults showed an age-related decrease in dermal (p = 0.021) and subcutis (p = 0.009) thicknesses. Pubertal girls had a thicker subcutis than pubertal boys in both thigh (16.7 vs 7.5 mm; p<0.0001) and abdomen (16.7 vs 8.8 mm; p<0.0001). Men had greater thigh dermal thickness than women (1.89 vs 1.65 mm; p = 0.003), while the subcutis was thicker in women in thigh (21.3 vs 17.9 mm; p = 0.012) and abdomen (17.7 vs 9.8 mm; p<0.0001). In boys, men, and women, both dermis and subcutis were thicker on the abdomen compared to thigh; in girls this was only so for dermal thickness. In both children and adults, the skin (dermis and subcutis) became steadily thicker with increasing BMI (p<0.0001).

Conclusions

Skin thickness is affected by age, pubertal status, gender, BMI, and anatomical site. Such differences may be important when considering appropriate sites for dermal/subcutaneous injections and other transdermal delivery systems.     

Relationship between Tumor Heterogeneity Measured on FDG-PET/CT and Pathological Prognostic Factors in Invasive Breast Cancer

Background

There is currently little support to understand which pathological factors led to differences in tumor texture as measured from FDG PET/CT images. We studied whether tumor heterogeneity measured using texture analysis in FDG-PET/CT images is correlated with pathological prognostic factors in invasive breast cancer.

Methods

Fifty-four patients with locally advanced breast cancer who had an initial FDG-PET/CT were retrospectively included. In addition to SUVmax, three robust textural indices extracted from 3D matrices: High-Gray-level Run Emphasis (HGRE), Entropy and Homogeneity were studied. Univariate and multivariate logistic regression was used to identify PET parameters associated with poor prognosis pathological factors: hormone receptor negativity, presence of HER-2 and triple negative phenotype. Receiver operating characteristic (ROC) curves and the (AUC) analysis, and reclassification measures, were performed in order to evaluate the performance of combining texture analysis and SUVmax for characterizing breast tumors.

Results

Tumor heterogeneity, measured with HGRE, was higher in negative estrogen receptor (p = 0.039) and negative progesterone receptor tumors (p = 0.036), and in Scarff-Bloom-Richardson grade 3 tumors (p = 0.047). None of the PET indices could identify HER-2 positive tumors. Only SUVmax was positively correlated with Ki-67 (p<0.0004). Triple negative breast cancer (TNBC) exhibited higher SUVmax (Odd Ratio = 1.22, 95%CI [1.06–1.39],p = 0.004), lower Homogeneity (OR = 3.57[0.98–12.5],p = 0.05) and higher HGRE (OR = 8.06[1.88–34.51],p = 0.005) than non-TNBC. Multivariate analysis showed that HGRE remained associated with TNBC (OR = 5.27[1.12–1.38],p = 0.03) after adjustment for SUVmax. Combining SUVmax and HGRE yielded in higher area under the ROC curves (AUC) than SUVmax for identifying TNBC: AUC =  0.83 and 0.77, respectively. Probability of correct classification also increased in 77% (10/13) of TNBC and 71% (29/41) of non-TNBC (p = 0.003), when combining SUVmax and HGRE.

Conclusions

Tumor heterogeneity measured on FDG-PET/CT was higher in invasive breast cancer with poor prognosis pathological factors. Texture analysis might be used, in addition to SUVmax, as a new tool to assess invasive breast cancer aggressiveness.     

The Duration of Hypotension Determines the Evolution of Bacteremia-Induced Acute Kidney Injury in the Intensive Care Unit

Background

Exploration of the impact of severe hypotension on the evolution of acute kidney injury in septic patients.

Methods and Results

We reviewed the hemodynamic parameters of 137 adults with septic shock and proven blood stream infection in the ICU. Severe hypotension was defined as a mean arterial blood pressure (MAP) ≤65 mmHg. The influence of the duration of severe hypotension on the evolution of acute kidney injury was evaluated according to the RIFLE classification, with day 0 defined as the day of a positive blood stream infection. After bloodstream infection, the probability for a patient to be in Failure was significantly higher than before blood stream infection (OR = 1.94, p = 0.0276). Patients have a significantly higher risk of evolving to Failure if the duration of severe hypotension is longer (OR = 1.02 for each 10 minutes increase in duration of a MAP <65 mmHg, p = 0.0472). A cut-off of at least 51 minutes of severe hypotension (<65 mmHg) or at least 5.5 periods of severe hypotension within 1 day identified patients with increased risk to evolve to Failure.

Conclusions

There is a significant influence of both the duration and the number of periods of severe hypotension on the evolution to Failure. Blood stream infection has a significantly negative effect on the relationship between severe hypotension and Failure.     

The Associations between Anthropometric Indices and Obstructive Sleep Apnea in a Korean Population

Background

Obesity is a major risk factor for the development of obstructive sleep apnea (OSA). Although clinical and epidemiological studies have shown that OSA and obesity are strongly associated, few Asian studies have examined the associations between anthropometric obesity indices and OSA, especially in the Korean population. The purpose of this study was to evaluate the influence of anthropometric obesity indices on OSA in a Korean population.

Methods

Anthropometric indices, including neck circumference, waist circumference, and body mass index, were assessed in 383 consecutive subjects with suspected OSA.

Results

Of the 383 subjects assessed, 316 (82.5%) were diagnosed with OSA. Neck circumference (r = 0.518), waist circumference (r = 0.570), and body mass index (r = 0.512) were correlated with the apnea-hypopnea index (p<0.001, for all). After adjusting for age, sex, alcohol consumption, and smoking, a logistic regression model showed that neck circumference [odds ratio (OR), 1.414; p<0.001)], waist circumference (OR, 1.114; p<0.001), and body mass index (OR, 1.364; p<0.001) were associated with OSA. The linear regression model showed that neck circumference (β = 3.748, p<0.001), waist circumference (β = 1.272, p<0.001), and body mass index (β = 3.082, p<0.001) were associated with apnea-hypopnea index. The cut-off values for predicting OSA were determined as 34.5 cm for neck circumference, 76.5 cm for waist circumference, and 23.05 kg/m² for body mass index for females, and 38.75 cm for neck circumference, 88.5 cm for waist circumference, and 24.95 kg/m² for body mass index for males.

Conclusion

Increased anthropometric indices were significantly associated with the presence and severity of OSA in a Korean population. In addition, this study demonstrated the cut-off values for body mass index, waist circumference, and neck circumference for increased OSA risk.     

Association between Gender,Process of Care Measures,and Outcomes in ACS in India: Results from the Detection and Management of Coronary Heart Disease (DEMAT) Registry

Background

Studies from high-income countries have shown that women receive less aggressive diagnostics and treatment than men in acute coronary syndromes (ACS), though their short-term mortality does not appear to differ from men. Data on gender differences in ACS presentation, management, and outcomes are sparse in India.

Methods and Results

The Detection and Management of Coronary Heart Disease (DEMAT) Registry collected data from 1,565 suspected ACS patients (334 women; 1,231 men) from ten tertiary care centers throughout India between 2007–2008. We evaluated gender differences in presentation, in-hospital and discharge management, and 30-day death and major adverse cardiovascular event (MACE; death, re-hospitalization, and cardiac arrest) rates. Women were less likely to present with STEMI than men (38% vs. 55%, p<0.001). Overall inpatient diagnostics and treatment patterns were similar between men and women after adjustment for potential confounders. Optimal discharge management with aspirin, clopidogrel, beta-blockers, and statin therapy was lower for women than men, (58% vs. 65%, p = 0.03), but these differences were attenuated after adjustment (OR = 0.86 (0.62, 1.19)). Neither the outcome of 30-day mortality (OR = 1.40 (0.62, 3.16)) nor MACE (OR = 1.00 (0.67, 1.48)) differed significantly between men and women after adjustment.

Conclusions

ACS in-hospital management, discharge management, and 30-day outcomes did not significantly differ between genders in the DEMAT registry, though consistently higher treatment rates and lower event rates in men compared to women were seen. These findings underscore the importance of further investigation of gender differences in cardiovascular care in India.     

The E-Wave Deceleration Rate E/DT Outperforms the Tissue Doppler-Derived Index E/e' in Characterizing Lung Remodeling in Heart Failure with Preserved Ejection Fraction

Background

Diastolic dysfunction in heart failure with preserved ejection fraction (HFpEF) may result in pulmonary congestion and lung remodeling. We evaluated the usefulness of major diastolic echocardiographic parameters and of the deceleration rate of early transmitral diastolic velocity (E/DT) in predicting lung remodeling in a rat model of HFpEF.

Methods and Results

Rats underwent aortic banding (AoB) to induce pressure overload (PO). Left ventricular hypertrophy fully developed 2 weeks after AoB. At 4 and 6 weeks, the lung weight-to-body weight ratio (LW/BW), a sensitive marker for pulmonary congestion and remodeling, dramatically increased despite preserved fractional shortening, indicating the presence of HFpEF. The time course of LW/BW was well reflected by E/DT, by the ratio of early to late transmitral diastolic velocity (E/A) and the deceleration time of E (DT), but not by the ratio of transmitral to mitral annular early diastolic velocity (E/e''). In agreement, the best correlation with LW/BW was found for E/DT (r = 0.76; p<0.0001), followed by E/A (r = 0.69; p<0.0001), DT (r = −0.62; p<0.0001) and finally E/e'' (r = 0.51; p<0.001). Furthermore, analysis of receiver-operating characteristic curves for the prediction of increased LW/BW revealed excellent area under the curve values for E/DT (AUC = 0.98) and DT (AUC = 0.95), which are significantly higher than that of E/e'' (AUC = 0.82). In a second approach, we also found that the new parameter E/DT correlated well with right ventricular weight index and echocardiographic measures of right ventricular systolic function.

Conclusions

The novel parameter E/DT outperforms the tissue Doppler index E/e'' in detecting and monitoring lung remodeling induced by pressure overload. The results may provide a handy tool to point towards secondary lung disease in HFpEF and warrant further clinical investigations.     

Risk Factors for Renal Scarring and Deterioration of Renal Function in Primary Vesico-Ureteral Reflux Children: A Long-Term Follow-Up Retrospective Cohort Study

Background and Purpose

The aim was to identify the risk factors for renal scarring and deteriorating renal function in children with primary vesico-ureteral reflux (VUR).

Materials and Methods

Patients with primary VUR admitted to the National Cheng Kung University Hospital were retrospectively analyzed. The outcomes were renal scarring, assessed by technetium-99 m dimercaptosuccinic acid scanning, and renal function, assessed by estimated glomerular filtration rate. Univariate and multivariate models were applied to identify the corresponding independent predictors.

Results

A total of 173 patients with primary VUR were recruited. The median age of VUR diagnosis was 10.0 months (IQR: 4.0–43.0 months). After adjusting for confounding factors, it was found that older age of VUR diagnosis (≥5 years vs. <1 year, adjusted OR = 2.78, 95% CI = 1.00–7.70, p = 0.049), higher grade of VUR (high grade [IV–V] vs. none, adjusted OR = 15.17, 95% CI = 5.33–43.19, p<0.0001; low grade [I–III] vs. none, adjusted OR = 5.72, 95% CI = 2.43–13.45, p<0.0001), and higher number of UTI (≥2 vs. 0, adjusted OR = 3.21, 95% CI = 1.06–9.76, p = 0.039) were risk factors for renal scarring, whereas a younger age of VUR diagnosis (≥5 years vs. <1 year, adjusted HR = 0.16, 95% CI: 0.05–0.51, p = 0.002), renal scarring (yes vs. no, adjusted HR = 3.66, 95% CI: 1.32–10.16, p = 0.013), and APN (yes vs. no, adjusted HR = 3.10, 95% CI: 1.05–9.14, p = 0.041) were risk factors for developing chronic kidney disease stage 2 or higher.

Conclusions

Our findings expand on the current knowledge of risk factors for renal scarring and deteriorating renal function, and this information can be used to modify the management and treatment of VUR.     

Stressful Events and Continued Smoking and Continued Alcohol Consumption during Mid-Pregnancy

Aim

to examine whether the severity of different categories of stressful events is associated with continued smoking and alcohol consumption during mid-pregnancy. Also, we explored the explanation of these associations by anxiety and depressive symptoms during pregnancy. Finally, we studied whether the severity of stressful events was associated with the amount of cigarettes and alcohol used by continued users.

Method

we conducted a cross-sectional analysis using data from a population-based prospective cohort study. Pregnant women were recruited via midwifery practices throughout The Netherlands. We analyzed women who continued smoking (n = 113) or quit (n = 290), and women who continued alcohol consumption (n = 124) or quit (n = 1403) during pregnancy. Smoking, alcohol consumption, and perceived severity of stressful events were measured at 19 weeks of gestation. The State Trait Anxiety Inventory and the Edinburgh Postnatal Depression Scale were filled out at 14 weeks of gestation. Odds ratios were calculated as association measures and indicated the relative increase for the odds of continuation of smoking and alcohol consumption for the maximum severity score compared to the minimum score.

Findings

severity of the following stressful event categories was associated with continued alcohol consumption: ‘conflict with loved ones’ (OR = 10.4, p<0.01), ‘crime related’ (OR = 35.7, p<0.05), ‘pregnancy-specific’ (OR = 13.4, p<0.05), and the total including all events (OR = 17.2, p<0.05). Adjustment for potential confounders (age, parity and educational level) did not notably change the estimates. There was no association of anxiety and depressive symptoms with continued smoking or alcohol consumption. No associations emerged for continued smoking and severity of stressful events. The amount of cigarettes and alcohol consumption among continued users was not associated with severity of stressful events.

Conclusions

Our findings may be relevant for health care providers, in particular midwives and general practitioners. The impact of stressful events may be considered when advising pregnant women on smoking and alcohol consumption.     

Decreased Leukocyte Telomere Length (LTL) Is Associated with Stroke but Unlikely to Be Causative

Aims

Interindividual variability in telomere length is highly heritable. Leukocyte telomere length (LTL) shortening has been shown to be associated with the process of atherosclerosis. But whether the inheritance of LTL is related to stroke is still unclear. The aim of this study was to test if telomere shortening was associated with stroke and whether this association was mainly due to inheritance or acquired cardiovascular risk factors.

Methods

Our study was focused on stroke in patients and their siblings. 450 subjects were recruited into this study: 150 patients with ischemic stroke as case group, 150 siblings of patients free of stroke (sibling group) and 150 healthy people as normal control. LTL was measured by real-time Polymerase Chain Reactions. The association between LTL and the cardiovascular risk factors was also determined.

Results

A significant decrease of LTL was found in case group when comparing with sibling (0.92±0.77 vs 1.68±1.24, p<0.001) and normal groups (0.92±0.77 vs 1.95±1.07, p<0.001), but no significant difference was found between sibling group and healthy control (p = 0.330). Shorter telomere length was independently associated with hypertension (p = 0.029, OR = 2.189, 95%CI:1.084–4.421), recent social pressure (p = 0.001, OR = 3.121, 95%CI:1.597–6.101), age (p = 0.004, OR = 1.055, 95%CI:1.017–1.093), HDL (p = 0.022, OR = 0.227, 95%CI:0.064–0.810) and diabetes (p = 0.018, OR = 3.174, 95%CI:1.221–8.252). Additionally, shortened length of telomere (p = 0.017, OR = 3.996, 95%CI:1.283–12.774) was an independent risk biomarker for stroke among case and sibling groups.

Conclusion

The present study has demonstrated that decreased LTL might be associated with ischemic stroke but unlikely to be causative.     

High Prevalence of Illicit Drug Use in Men Who Have Sex with Men with HIV-1 Infection in Japan

Objective

To examine the prevalence of illicit drug use among men who have sex with men (MSM) with HIV-1 infection in Japan, where the life-time prevalence of illicit drug use in the general population is only 2.9%.

Design

A single-center cross-sectional study at a large HIV clinic in Tokyo, which treats approximately 15% of HIV-1 infected patients in Japan.

Methods

The prevalence of illicit drug use and the assciation of characteristics and social demographics of the patients with illicit drug use were examined. Patients who visited the clinic for the first time from 2005 to 2010 were enrolled. Relevant variables were collected using a structured interview and from the medical records. Multivariate logistic regression analyses were applied to estimate the odds of association of MSM over non-MSM HIV-infected patients with illicit drug use.

Results

1,196 patients were enrolled. They were mostly Japanese men of relatively young age. Illicit drug use (including injection drugs) was reported by 35% of the patients (by 40% of MSM), and 4% were IDU while 5% were on methamphetamine. 2% of the population was arrested due to illicit drugs. MSM was significantly associated with illicit drug use (adjusted OR = 4.60; 95% CI, 2.88–7.36; p<0.01). Subgroup analysis of the patients stratified by three age groups (≤30, 31 to 40, and >40) showed that the odds of association of MSM with illicit drug use was the strongest in the youngest age group (≤30 years: adjusted OR = 7.56; 95% CI, 2.86–20.0; p<0.01), followed by the oldest (>40 years: adjusted OR = 6.15; 95% CI, 2.40–15.8; p<0.01), and the weakest in the group aged 31 to 40 (adjusted OR = 3.39; 95% CI, 1.73–6.63; p<0.01).

Conclusions

The prevalence of illicit drug use is high among MSM patients with HIV-1 infection in Japan. Effective intervention for illicit drug use in this population is warranted.     

A Meta-Analysis of the Association between the CC Chemokine Ligand 5 (CCL5) -403 G>A Gene Polymorphism and Tuberculosis Susceptibility

Aim

Many case-control studies have been performed in the recent past to investigate the association between CCL5 -403 G>A (rs2107538) gene polymorphism and tuberculosis (TB) susceptibility in various ethnic groups. However, these studies have produced inconsistent and contradictory results. In the present study, meta-analysis was performed to assess the association between CCL5 -403 G>A polymorphism and TB risk.

Methodology

Quantitative synthesis was done for the published studies based upon association between CCL5 -403 G>A polymorphism and TB risk from PubMed (Medline), EMBASE web search. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for allele contrast, homozygous, heterozygous, dominant and recessive genetic models.

Results

A total of six studies comprising 1638 confirmed TB cases and 1519 healthy controls were included in this meta-analysis. Variant A allele (A vs. G: p = 0.035; OR = 1.301, 95% CI = 1.019 to 1.662) and variant homozygous (AA vs. GG; p = 0.001; OR = 1.520, 95% CI = 1.202 to 1.923) carriers were significantly associated with TB susceptibility. Similarly, recessive model (AA vs. GG+GA: p = 0.016; OR = 1.791, 95% CI = 1.117 to 2.873) also indicated increased TB risk. Whereas, heterozygous (GA vs. GG: p = 0.837; OR = 1.028, 95% CI = 0.791 to 1.335) and dominant (AA+GA vs. GG: p = 0.222; OR = 1.188, 95% CI = 0.901 to 1.567) models failed to show increased risk of developing TB.

Conclusions

This meta-analysis suggests that there is a significant association between the CCL5 -403 G>A polymorphism and increased risk of TB. However, larger well-designed epidemiological studies with stratified case control and biological characterization may be helpful to validate this association.     

Histological Criteria for Encapsulating Peritoneal Sclerosis – A Standardized Approach

Background

The two most relevant pathologies of long-term peritoneal dialysis (PD) are simple sclerosis and encapsulating peritoneal sclerosis (EPS). The histological differentiation of those two entities is difficult. The Aim of the study was to establish a method to standardize and facilitate the differentiation between simple sclerosis and EPS

Methods

We investigated 58 peritoneal biopsies - 31 EPS patients and 27 PD patients. Two blinded investigators analyzed 20 histological characteristics in EPS and PD patients.

Results

The following findings were significantly more common in EPS than in patients on PD without EPS: fibroblast like cells (FLC) (p<0.0001), mesothelial denudation (p<0.0001), decreased cellularity (p = 0.008), fibrin deposits (p<0.03), Fe deposits (p = 0.05), podoplanin vascular (p<0.0001), podoplanin avascular (p<0.0001). Using all predictor variables we trained the classification method Random Forest to categorize future cases. Podoplanin vascular and avascular were taken together (p<0.0001), FLC (p<0.0001), mesothelial denudation (p = 0.0005), calcification (p = 0.0026), acellular areas (p = 0.0094), and fibrin deposits (p = 0.0336) showed up as significantly important predictor variables. Estimated misclassification error rate when classifying new cases turned out to be 14%.

Conclusion

The introduced statistical method allows discriminating between simple sclerosis and EPS. The misclassification error will likely improve with every new case added to the database.     

Potential Role of M. tuberculosis Specific IFN-γ and IL-2 ELISPOT Assays in Discriminating Children with Active or Latent Tuberculosis

Background

Although currently available IGRA have been reported to be promising markers for TB infection, they cannot distinguish active tuberculosis (TB) from latent infection (LTBI).

Objective

Children with LTBI, active TB disease or uninfected were prospectively evaluated by an in-house ELISPOT assay in order to investigate possible immunological markers for a differential diagnosis between LTBI and active TB.

Methods

Children at risk for TB infection prospectively enrolled in our infectious disease unit were evaluated by in-house IFN-γ and IL-2 based ELISPOT assays using a panel of Mycobacterium tuberculosis antigens.

Results

Twenty-nine children were classified as uninfected, 21 as LTBI and 25 as active TB cases (including 5 definite and 20 probable cases). Significantly higher IFN-γ ELISPOT responses were observed in infected vs. uninfected children for ESAT-6 (p<0.0001), CFP-10 (p<0.0001), TB 10.3 (p = 0.003), and AlaDH (p = 0.001), while differences were not significant considering Ag85B (p = 0.063), PstS1 (p = 0.512), and HspX (16 kDa) (p = 0.139). IL-2 ELISPOT assay responses were different for ESAT-6 (p<0.0001), CFP-10 (p<0.0001), TB 10.3 (p<0.0001), HspX (16 kDa) (p<0.0001), PstS1 (p<0.0001) and AlaDH (p = 0.001); but not for Ag85B (p = 0.063). Comparing results between children with LTBI and those with TB disease differences were significant for IFN-γ ELISPOT only for AlaDH antigen (p = 0.021) and for IL-2 ELISPOT assay for AlaDH (p<0.0001) and TB 10.3 antigen (p = 0.043). ROC analyses demonstrated sensitivity of 100% and specificity of 81% of AlaDH-IL-2 ELISPOT assay in discriminating between latent and active TB using a cut off of 12.5 SCF per million PBMCs.

Conclusion

Our data suggest that IL-2 based ELISPOT with AlaDH antigen may be of help in discriminating children with active from those with latent TB.     

Age and Gender Differences in the Social Patterning of Cardiovascular Risk Factors in Switzerland: The CoLaus Study

Objectives

We examined the social distribution of a comprehensive range of cardiovascular risk factors (CVRF) in a Swiss population and assessed whether socioeconomic differences varied by age and gender.

Methods

Participants were 2960 men and 3343 women aged 35–75 years from a population-based survey conducted in Lausanne, Switzerland (CoLaus study). Educational level was the indicator of socioeconomic status used in this study. Analyses were stratified by gender and age group (35–54 years; 55–75 years).

Results

There were large educational differences in the prevalence of CVRF such as current smoking (Δ = absolute difference in prevalence between highest and lowest educational group:15.1%/12.6% in men/women aged 35–54 years), physical inactivity (Δ = 25.3%/22.7% in men/women aged 35–54 years), overweight and obesity (Δ = 14.6%/14.8% in men/women aged 55–75 years for obesity), hypertension (Δ = 16.7%/11.4% in men/women aged 55–75 years), dyslipidemia (Δ = 2.8%/6.2% in men/women aged 35–54 years for high LDL-cholesterol) and diabetes (Δ = 6.0%/2.6% in men/women aged 55–75 years). Educational inequalities in the distribution of CVRF were larger in women than in men for alcohol consumption, obesity, hypertension and dyslipidemia (p<0.05). Relative educational inequalities in CVRF tended to be greater among the younger (35–54 years) than among the older age group (55–75 years), particularly for behavioral CVRF and abdominal obesity among men and for physiological CVRF among women (p<0.05).

Conclusion

Large absolute differences in the prevalence of CVRF according to education categories were observed in this Swiss population. The socioeconomic gradient in CVRF tended to be larger in women and in younger persons.