Circulating Vitamin D Level and Risk of Sudden Cardiac Death and Cardiovascular Mortality: A Dose-Response Meta-Analysis of Prospective Studies.

BACKGROUND: We conducted a comprehensive meta-analysis of prospective cohort studies to analyze the effect of circulating vitamin D level on the risk of sudden cardiac death (SCD) and cardiovascular disease (CVD) mortality. METHODS: Prospective cohort studies evaluating the association between circulating vitamin D and risk of SCD and CVD mortality were systematically searched in the PubMed and Embase. Extracted data were analyzed using a random effects model and results were expressed in terms of hazard ratio (HR) and 95% confidence interval (CI). Restricted cubic spline analysis was used to estimate the dose-response relationships. RESULTS: Of the 1,321 records identified using the search strategy, a total of 19 cohort studies were included in the final meta-analysis. The pooled estimate of HR (95% CI) for low vs. high circulating vitamin D level was 1.75 (1.49-2.06) with I² value of 30.4%. In subgroup analysis, strong effects of circulating vitamin D were observed in healthy general population (pooled HR, 1.84; 95% CI, 1.43-2.38) and the clinical endpoint of SCD (pooled HRs, 2.68; 95% CI, 1.48-4.83). The dose-response analysis at the reference level of < 50 nmol/L showed a significant negative association between circulating vitamin D and risk of SCD and CVD mortality. CONCLUSION: Our meta-analysis of prospective cohort studies showed that lower circulating vitamin D level significantly increased the risk of SCD and CVD mortality.

Gender and Age Bias in the Evaluation of Suicide Attempt Behavior in an Emergency Department.

We aimed to investigate whether demographic characteristics such as age and gender of attempted suicide patients are associated with bias in the post-Emergency Department (ED) discharge program manager's evaluation of genuineness of the patients' suicide attempts. In the ED-Based Post-Suicide Attempt Case Management (ED-PSACM) program, the manager interviews patients with suicide attempts and makes subjective judgement on the patient's genuineness of the suicide attempt. After patients' discharge, the manager provides follow-up post-discharge care management services. Compared to ≥ 65 years old male patients as a reference group, 18-39 years old female patients showed significantly lower judgment for a genuine suicide attempt (OR = 0.34; 95% CI 0.12-0.81). Other groups did not show significant differences from the reference group. Our study result suggests the possibility of the effects of bias on young females on the judgment of the suicide attempt genuineness. Medical staff and interventions managers in the ED should be concerned to avoid knowledge-mediated bias, especially by gender and age.

Cystatin C and mortality risk in the general population: systematic review and dose response meta-analysis.

INTRODUCTION: Cystatin C has been identified as an independent predictor of all-cause and cardiovascular mortality in the general population. This meta-analysis to evaluate the association between serum cystatin C level and all-cause and cardiovascular mortality. We additionally conducted a dose-response analysis to examine a linear association between cystatin C and cardiovascular mortality. METHODS: PudMed and Embase databases were searched until January, 2021. All prospective cohort studies that reported a multivariate-adjusted risk estimated of all-cause and cardiovascular mortality for the highest compared with lowest cystatin C level were included. RESULTS: 13 prospective cohort studies, a total of 57,214 participants were included in this analysis. Meta-analysis indicated that the highest compared with lowest cystatin C level was associated with an increase of all-cause mortality (hazard ratio [HR]: 2.01; 95% confidence intervals [CI]: 1.60-2.53; I2=89%) and cardiovascular mortality (2.62 [1.96-3.51]; I2=52%). We found a significant log-linear dose-response association between cystatin C and cardiovascular mortality (p < 0.01). Every 0.1 mg/L increase in cystatin C level was associated with a 7.3% increased cardiovascular mortality. CONCLUSIONS: Elevated serum cystatin C is associated with an increased risk of all-cause and cardiovascular mortality in the general populations. Particularly, cystatin C level and cardiovascular mortality showed linear correlation.

Effect of implementation of multi-tier response system and prolonged on-scene resuscitation for out-of-hospital cardiac arrest.

INTRODUCTION: The purpose of this study was to explain the process and results of implementing a bundle of two cardiopulmonary resuscitation (CPR) programs in Gwang-ju metropolitan city and to determine whether the use of these programs improved the clinical outcomes for out-of-hospital cardiac arrest (OHCA) patients. METHODS: This was a before- and after-intervention study of the implementation of a bundle of two CPR programs in Gwang-ju. The main intervention was a multi-tier response (MTR) system, with an emphasis on prolonged on-scene resuscitation. The primary outcome was good neurological recovery, and secondary outcomes were survival to discharge and prehospital return of spontaneous circulation (ROSC). A multivariable logistic regression model was used to estimate the association between the study period and outcomes, after adjusting for potential confounders. Interaction analysis was conducted to determine whether the location of arrest and witness status modified the effect of the study period on the study outcomes. RESULTS: The adjusted odds ratios (AORs) for the intervention were 1.35 (0.96-1.90) for pre-hospital ROSC, 1.19 (0.49-2.86) for survival to discharge, and 3.45 (1.01-11.80) for good CPC. The AORs for good neurological recovery of the after-intervention period were 2.93 (0.73-11.77) for a private place, 4.82 (1.04-22.39) for a public place, 5.88 (1.47-23.57) for a witnessed arrest, and 1.49 (0.28-7.86) for a non-witnessed arrest. CONCLUSIONS: OHCA patients treated in the after-intervention period with the bundle of CPR programs including MTR and prolonged on-scene resuscitation showed better clinical outcomes, especially pre-hospital ROSC, and neurological recovery at hospital discharge than those treated in the before-intervention period.

Assessment of novel ICT-EMS systems to improve emergency patient transportation during the COVID-19 pandemic.

OBJECTIVES: This study aimed to examine the usability, feasibility, acceptability, and appropriateness of the information and communication technology for emergency medical services (ICT-EMS) systems to improve the transportation of emergency patients during the COVID-19 pandemic. METHODS: Emergency medical technicians (EMTs) (n = 229) employed at 7 fire stations operated by the North Chungcheong Fire Service Headquarters, South Korea were trained to use ICT-EMS devices prior to a 1-month implementation period. System Usability Scale (SUS), Feasibility of Intervention Measure (FIM), Acceptability of Intervention Measure (AIM), and Intervention Appropriateness Measure (IAM) questionnaires were conducted in the 4th week of the 1-month implementation period to assess the perceived usability, feasibility, acceptability, and appropriateness of the ICT-EMS systems. RESULTS: Among a total of 229 EMTs, 187 EMTs (81.7%) completed the survey. The overall SUS score was significantly low (score of 35.6) indicating an overall negative perception of the ICT-EMS systems. With regard to the feasibility, acceptability, and intervention appropriateness of ICT-EMS, roughly 50 (26.7%) participants agreed that ICT-EMS implementation was possible, appealing, and suitable. CONCLUSION: Many potential areas of improvement were identified within the ICT-EMS systems. System alterations regarding usability, feasibility, acceptability, and appropriateness may be necessary to successfully implement the ICT-EMS systems.

Effectiveness of negative pressure isolation stretcher and rooms for SARS-CoV-2 nosocomial infection control and maintenance of South Korean emergency department capacity.

OBJECTIVE: There are growing concerns regarding the lack of COVID-19 pandemic response capacity in already overwhelmed emergency departments (EDs), and lack of proper isolation facilities. This study evaluated the effectiveness of the negative pressure isolation stretcher (NPIS) and additional negative pressure isolation rooms (NPIRs) on the maintenance of emergency care capacity during the COVID-19 outbreak. METHODS: A before and after intervention study was performed between February 27, 2020 and March 31, 2020 at the ED of Chungbuk National University Hospital, Cheongju, South Korea. A total of 2455 patients who visited the ED during the study period were included. Interventions included the introduction of the NPIS and additional NPIRs in the ED. The main outcome of the study was frequency of medical cessation. Secondary outcomes were the average number of ED visits and lengths of stay. RESULTS: After the intervention, average frequency of medical cessation was significantly decreased from 1.6 times per day (range 0-4) in the pre-intervention period to 0.6 times per day (range 0-3) in the post-intervention period (p-value <0.01). On the other hand, the number of patients visiting the ED increased significantly from 67.2 persons per day (range 58-79) pre-intervention to 76.3 persons per day (range 61-88) post-intervention (p value <0.01). However, there were no statistically significant differences in the average ED length of stay across the study phases (p value = 0.50). CONCLUSIONS: This intervention may provide an effective way to prepare and meet the ED response needs of the COVID-19 pandemic.

Posttraumatic stress disorder and risk of selected autoimmune diseases among US military personnel.

BACKGROUND: Increasing evidence suggests a link between posttraumatic stress disorder (PTSD) and physical health. Stress disorders may lead to impairment of the immune system and subsequent autoimmune disease. This study investigated the association between PTSD and risk of selected autoimmune diseases (i.e. rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel diseases, and multiple sclerosis) among US active duty service members. METHODS: Using data from the Millennium Cohort Study, incident autoimmune cases between study initiation and September 2015 were identified from medical encounter records in the Military Health System Data Repository (MDR). Participants were classified as having a history of PTSD if they self-reported receiving a health care provider's diagnosis of PTSD or if they screened positive using the PTSD Checklist-Civilian Version. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression models adjusted for demographics and history of another mental health condition. RESULTS: Among 120,572 participants followed for a mean of 5.2 years, risk of any of the selected autoimmune diseases was 58% higher for those with a history of PTSD (HR = 1.58, 95% CI: 1.25, 2.01) compared with no history of PTSD. Further adjustment for BMI, smoking status, and alcohol use had little impact on the effect estimates, and results were not appreciably different according to combat experience and history of physical or sexual trauma. CONCLUSIONS: Active duty military personnel with PTSD may have an elevated risk of a range of autoimmune diseases, regardless of combat experience or prior trauma. Future research is needed to understand potential mechanisms which may inform future mitigative strategies in reducing extra-neuropsychiatric health problems among those with PTSD.

Association between ambient PM2.5 and emergency department visits for psychiatric emergency diseases.

BACKGROUND: Whether or not short-term exposure to particulate matter <2.5 µm in diameter (PM2.5) increases the risk of psychiatric emergency diseases is unclear. METHODS: The study was performed in a metropolis from January 2015 to December 2016. The exposure was PM2.5, and the confounders were weather (temperature and humidity) and other pollutants (PM10, SO2, CO, O3, and NO2). The outcomes were emergency department (ED) visits with psychiatric disease codes (F00-F99 in ICD10 codes). General additive models were used for the statistical analysis to calculate the adjusted relative risks (ARRs) and 95% confidence intervals (95% CIs) for the daily number of ED visits with a lag of 1 to 3 days following a 10 µg/m3 increase in PM2.5. RESULTS: During the study period, a total of 67,561 ED visits for psychiatric diseases were identified and tested for association with PM2.5. Daily ED visits for all psychiatric diseases were not associated with PM2.5 in the model that was not adjusted for other pollutants. The ARR (95% CI) in the model adjusted for SO2 was 1.011 (1.002-1.021) by 10 µg/m3 of PM2.5 on Lag 1 for all psychiatric diseases (F00-F99). The ARR (95% CI) in the model adjusted for O3 was 1.015 (1.003-1.029) by 10 µg/m3 of PM2.5 on Lag 1 for F40-F49 (Neurotic, stress-related and somatoform disorders). CONCLUSION: An increase in PM2.5 showed a significant association with an increase in ED visits for all psychiatric diseases (F00-F99) and for neurotic, stress-related and somatoform disorders (F40-F49) on lag day 1.

Gender disparities in percutaneous coronary intervention in out-of-hospital cardiac arrest.

BACKGROUND: Quality of post-arrest care is considered a significant factor for overall survival and neurological outcomes in out-of-hospital cardiac arrest (OHCA). However, previous studies suggested gender differences in invasive treatments including percutaneous coronary intervention (PCI). In this study, we evaluated gender disparities in the delivery of PCI among OHCA patients. METHODS: All adults OHCA patients with presumed cardiac etiology and sustained ROSC between 2013 and 2016 were included in the study. Main exposure was gender and primary outcome was PCI treatment. Multivariable logistic regression was used to analyze the association between gender and PCI treatment, adjusting for patient, community, prehospital, and hospital factors. The time interval from return of spontaneous circulation (ROSC) to PCI and survival outcomes were also analyzed as secondary and tertiary outcomes. RESULTS: A total of 20,675 patients were included for final analysis. Multivariable analysis showed that female patients were significantly less likely to receive PCI compared to males with adjusted odds ratio (OR) of 0.40 (95% CI 0.30-0.53). However, among those who received PCI, there were no significant associations between gender and time from ROSC to PCI (≤90 vs. >90 min). Overall survival outcomes were not significantly associated with gender after adjusting for PCI and other confounding factors (OR = 0.87, 95% CI 0.71-1.08 for survival to discharge and OR = 0.87, 95% CI 0.70-1.08 for good neurological recovery). CONCLUSIONS: Among sustained ROSC patients following OHCA, female patients were significantly less likely to undergo PCI than males. Further studies are warranted to reduce gender disparities in caring for post-arrest patients.

Location of arrest and effect of prehospital advanced airway management after emergency medical service-witnessed out-of-hospital cardiac arrest: nationwide observational study.

OBJECTIVES: To investigate the association of prehospital advanced airway management (AAM) on outcomes of emergency medical service (EMS)-witnessed out-of-hospital cardiac arrest (OHCA) according to the location of arrest. METHODS: We evaluated a Korean national OHCA database from 2012 to 2016. Adults with EMS-witnessed, non-traumatic OHCA were included. Patients were categorised into four groups according to whether prehospital AAM was conducted (yes/no) and location of arrest ('at scene' or 'in the ambulance'). The primary outcome was discharge with good neurological recovery (cerebral performance category 1 or 2). Multivariable logistic regression analysis was conducted to evaluate the association between AAM and outcome according to the location of arrest. RESULTS: Among 6620 cases, 1425 (21.5%) cases of arrest occurred 'at the scene', and 5195 (78.5%) cases of arrest occurred 'in an ambulance'. Prehospital AAM was performed in 272 (19.1%) OHCAs occurring 'at the scene' and 645 (12.4%) OHCAs occurring 'in an ambulance'. Patients with OHCA in the ambulance who had prehospital AAM showed the lowest good neurological recovery rate (6.0%) compared with OHCAs in the ambulance with no AAM (8.9%), OHCA at scene with AAM (10.7%) and OHCA at scene with no AAM (7.7%). For OHCAs occurring in the ambulance, the use of AAM had an adjusted OR of 0.67 (95% CI 0.45 to 0.98) for good neurological recovery. CONCLUSION: Our data show no benefit of AAM in patients with EMS-witnessed OHCA. For patients with OHCA occurring in the ambulance, AAM was associated with worse clinical outcome.

Interactive Effect between On-Scene Hypoxia and Hypotension on Hospital Mortality and Disability in Severe Trauma.

BACKGROUND: It is unclear whether effect size of the hypoxia is different on in-hospital mortality and disability according to hypotension status in the field. METHODS: Adult severe trauma (ST) patients during 2012-13 who were treated by emergency medical services (EMS) and had abnormal revised trauma scores in the field or who had positive trauma triage criteria were analyzed. Exposure was hypoxia (<94%) measured by EMS. End points were hospital mortality and disability defined as a Glasgow Outcome Scale that decreased by 2 points or more. Multivariable logistic regression with interaction model between hypoxia and hypotension was used for outcomes to calculate the adjusted odds ratios (AOR) with 95% confidence intervals (95% CIs) after adjusting for potential confounders. RESULTS: A total of 17,406 EMS-ST patients were analyzed. Of those, 2,598 (14.9%) died, and 3,292 (21.5%) were considered disabled at discharge. The total hypoxia group showed higher mortality and disability indices (35.7 and 51.2%) than the non-hypoxia group (10.7 and 15.9%) (each p-value < 0.0001). The AOR of hypoxia was 2.15 (1.92-2.40) for mortality and was 1.97 (1.75-2.21) for disability. In the interaction model, AORs for mortality by hypoxia in the hypotensive and non-hypotensive groups were 2.66 (2.32-3.04) and 1.74 (1.61-1.87), respectively (P < 0.0001 for interaction). The AORs for disability in the hypotensive and non-hypotensive groups were 2.17 (1.87-2.53) and 1.55 (1.42-1.69), respectively (P < 0.0001 for interaction). CONCLUSIONS: The effect of hypoxia was much greater in the hypotensive group than in the non-hypotensive group both in terms of mortality and disability.

Pan-Asian Trauma Outcomes Study (PATOS): Rationale and Methodology of an International and Multicenter Trauma Registry.

BACKGROUND: Trauma is a major health burden and a time-dependent critical emergency condition among developing and developed countries. In Asia, trauma has become a rapidly expanding epidemic and has spread out to many underdeveloped and developing countries through rapid urbanization and industrialization. Most casualties of severe trauma, which results in significant mortality and disability are assessed and transported by prehospital providers including physicians, professional providers, and volunteer providers. Trauma registries have been developed in mostly developed countries and measure care quality, process, and outcomes. In general, existing registries tend to focus on inhospital care rather than prehospital care. METHODS: The Pan-Asia Trauma Outcomes Study (PATOS) was proposed in 2013 and initiated in November, 2015 in order to establish a collaborative standardized study to measure the capabilities, processes and outcomes of trauma care throughout Asia. The PATOS is an international, multicenter, and observational research network to collect trauma cases transported by emergency medical services (EMS) providers. Data are collected from the participating hospital emergency departments in various countries in Asia which receive trauma patients from EMS. Data variables collected include 1) injury epidemiologic factors, 2) EMS factors, 3) emergency department care factors, 4) hospital care factors, and 5) trauma system factors. The authors expect to achieve a sample size of 67,230 cases over the next 2 years of data collection to analyze the association between potential risks and outcomes of trauma. CONCLUSION: The PATOS network is expected to provide comparison of the trauma EMS systems and to benchmark best practice with participating communities.

Cardiac arrest while exercising on mountains in national or provincial parks: A national observational study from 2012 to 2015.

BACKGROUND: Previous studies on cardiac arrest in mountainous areas were focused on environmental features such as altitude and temperature. However, those are limited to factors affecting the prognosis of patients after cardiac arrest. We analyzed the cardiac arrests in national or provincial parks located in the mountains and determined the factors affecting the prognosis of patients after cardiac arrest. METHODS: This study included all emergency medical service (EMS) treated patients over the age of 40 experiencing out-of-hospital cardiac arrests (OHCAs) of presumed cardiac etiology during exercise, between January 2012 and December 2015. The main focus of interest was the location of cardiac arrest occurrence (national mountain parks and provincial parks vs. other sites). The main outcome was survival to discharge and multivariable logistic regression was performed to adjust for possible confounding effects. RESULTS: A total 1835 patients who suffered a cardiac arrest while exercising were included. From these, 68 patients experienced cardiac arrest in national or provincial parks, and 1767 occurred in other locations. The unadjusted and adjusted ORs (95% CI) for a good cerebral performance scale (CPC) were 0.09 (0.01-0.63) and 0.08(0.01-0.56), survival discharges were 0.13(0.03-0.53) and 0.11 (0.03-0.48). CONCLUSIONS: Cardiac arrests occurring while exercising in the mountainous areas have worse prognosis compared to alternative locations.

A Nested Case-Control Study of Metabolically Defined Body Size Phenotypes and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC).

BACKGROUND: Obesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia) have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic) overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown. METHODS AND FINDINGS: The association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI) measurements to create four metabolic health/body size phenotype categories: (1) metabolically healthy/normal weight (BMI < 25 kg/m2), (2) metabolically healthy/overweight (BMI ≥ 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI < 25 kg/m2), and (4) metabolically unhealthy/overweight (BMI ≥ 25 kg/m2). Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥94 cm for men]) were used (instead of BMI) to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of <0.05 was considered statistically significant. In multivariable-adjusted conditional logistic regression models with BMI used to define adiposity, compared with metabolically healthy/normal weight individuals, we observed a higher colorectal cancer risk among metabolically unhealthy/normal weight (odds ratio [OR] = 1.59, 95% CI 1.10-2.28) and metabolically unhealthy/overweight (OR = 1.40, 95% CI 1.01-1.94) participants, but not among metabolically healthy/overweight individuals (OR = 0.96, 95% CI 0.65-1.42). Among the overweight individuals, lower colorectal cancer risk was observed for metabolically healthy/overweight individuals compared with metabolically unhealthy/overweight individuals (OR = 0.69, 95% CI 0.49-0.96). These associations were generally consistent when waist circumference was used as the measure of adiposity. To our knowledge, there is no universally accepted clinical definition for using C-peptide level as an indication of hyperinsulinaemia. Therefore, a possible limitation of our analysis was that the classification of individuals as being hyperinsulinaemic-based on their C-peptide level-was arbitrary. However, when we used quartiles or the median of C-peptide, instead of tertiles, as the cut-point of hyperinsulinaemia, a similar pattern of associations was observed. CONCLUSIONS: These results support the idea that individuals with the metabolically healthy/overweight phenotype (with normal insulin levels) are at lower colorectal cancer risk than those with hyperinsulinaemia. The combination of anthropometric measures with metabolic parameters, such as C-peptide, may be useful for defining strata of the population at greater risk of colorectal cancer.

Intrapancreatic distal common bile duct carcinoma: Analysis, staging considerations, and comparison with pancreatic ductal and ampullary adenocarcinomas.

Distal common bile duct carcinoma is a poorly characterized entity for reasons such as variable terminology and difficulty in determining site of origin of intrapancreatic lesions. We compared clinicopathologic features of pancreatobiliary-type adenocarcinomas within the pancreas, but arising from the distal common bile duct, with those of pancreatic and ampullary origin. Upon careful review of 1017 pancreatoduodenectomy specimens with primary adenocarcinoma, 52 (5%) qualified as intrapancreatic distal common bile duct carcinoma. Five associated with an intraductal papillary neoplasm were excluded; the remaining 47 were compared to 109 pancreatic ductal adenocarcinomas and 133 ampullary carcinomas. Distal common bile duct carcinoma patients had a younger median age (58 years) than pancreatic ductal adenocarcinoma patients (65 years) and ampullary carcinoma patients (68 years). Distal common bile duct carcinoma was intermediate between pancreatic ductal adenocarcinoma and ampullary carcinoma with regard to tumor size and rates of node metastases and margin positivity. Median survival was better than for pancreatic ductal adenocarcinoma (P=0.0010) but worse than for ampullary carcinoma (P=0.0006). Distal common bile duct carcinoma often formed an even band around the common bile duct and commonly showed intraglandular neutrophil-rich debris and a small tubular pattern. Poor prognostic indicators included node metastasis (P=0.0010), lymphovascular invasion (P=0.0299), and margin positivity (P=0.0069). Categorizing the tumors based on size also had prognostic relevance (P=0.0096), unlike categorization based on anatomic structures invaded. Primary distal common bile duct carcinoma is seen in younger patients than pancreatic ductal adenocarcinoma or ampullary carcinoma. Its prognosis is significantly better than pancreatic ductal adenocarcinoma and worse than ampullary carcinoma, at least partly because of differences in clinical presentation. Use of size-based criteria for staging appears to improve its prognostic relevance. Invasive pancreatobiliary-type distal common bile duct carcinomas are uncommon in the West and have substantial clinicopathologic differences from carcinomas arising from the pancreas and ampulla.

Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort.

Suboptimal intakes of the micronutrient selenium (Se) are found in many parts of Europe. Low Se status may contribute to colorectal cancer (CRC) development. We assessed Se status by measuring serum levels of Se and Selenoprotein P (SePP) and examined the association with CRC risk in a nested case-control design (966 CRC cases; 966 matched controls) within the European Prospective Investigation into Cancer and Nutrition. Se was measured by total reflection X-ray fluorescence and SePP by immunoluminometric sandwich assay. Multivariable incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Respective mean Se and SePP levels were 84.0 µg/L and 4.3 mg/L in cases and 85.6 µg/L and 4.4 mg/L in controls. Higher Se concentrations were associated with a non-significant lower CRC risk (IRR = 0.92, 95% CI: 0.82-1.03 per 25 µg/L increase). However, sub-group analyses by sex showed a statistically significant association for women (p(trend) = 0.032; per 25 µg/L Se increase, IRR = 0.83, 95% CI: 0.70-0.97) but not for men. Higher SePP concentrations were inversely associated with CRC risk (p(trend) = 0.009; per 0.806 mg/L increase, IRR = 0.89, 95% CI: 0.82-0.98) with the association more apparent in women (p(trend) = 0.004; IRR = 0.82, 95% CI: 0.72-0.94 per 0.806 mg/L increase) than men (p(trend) = 0.485; IRR = 0.98, 95% CI: 0.86-1.12 per 0.806 mg/L increase). The findings indicate that Se status is suboptimal in many Europeans and suggest an inverse association between CRC risk and higher serum Se status, which is more evident in women.

Plasma fetuin-A concentration, genetic variation in the AHSG gene and risk of colorectal cancer.

Fetuin-A, also referred to as α2-Heremans-Schmid glycoprotein (AHSG), is a liver protein known to inhibit insulin actions. Hyperinsulinemia is a possible risk factor for colorectal cancer; however, the role of fetuin-A in the development of colorectal cancer is unclear. We investigated the association between circulating fetuin-A and colorectal cancer risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Fetuin-A concentrations were measured in prediagnostic plasma samples from 1,367 colorectal cancer cases and 1,367 matched controls. In conditional logistic regression models adjusted for potential confounders, the estimated relative risk (95% confidence interval) of colorectal cancer per 40 µg/mL higher fetuin-A concentrations (approximately one standard deviation) was 1.13 (1.02-1.24) overall, 1.21 (1.05-1.39) in men, 1.06 (0.93-1.22) in women, 1.13 (1.00-1.27) for colon cancer and 1.12 (0.94-1.32) for rectal cancer. To improve causal inference in a Mendelian Randomization approach, five tagging single nucleotide polymorphisms of the AHSG gene were genotyped in a subset of 456 case-control pairs. The AHSG allele-score explained 21% of the interindividual variation in plasma fetuin-A concentrations. In instrumental variable analysis, genetically raised fetuin-A was not associated with colorectal cancer risk (relative risk per 40 µg/mL genetically determined higher fetuin-A was 0.98, 95% confidence interval: 0.73-1.33). The findings of our study indicate a modest linear association between fetuin-A concentrations and risk of colorectal cancer but suggest that fetuin-A may not be causally related to colorectal cancer development.

Calculation of the Ki67 index in pancreatic neuroendocrine tumors: a comparative analysis of four counting methodologies.

Ki67 index is now an essential part of classification of pancreatic neuroendocrine tumors. However, its adaptation into daily practice has been fraught with challenges related to counting methodology. In this study, three reviewers used four counting methodologies to calculate Ki67 index in 68 well-differentiated pancreatic neuroendocrine tumors: (1) 'eye-ball' estimation, which has been advocated as reliable and is widely used; (2) automated counting by image analyzer; (3) manual eye-counting (eye under a microscope without a grid); and (4) manual count of camera-captured/printed image. Pearson's correlation (R) was used to measure pair-wise correlation among three reviewers using all four methodologies. Average level of agreement was calculated using mean of R values. The results showed that: (1) 'eye-balling' was least expensive and fastest (average time <1 min) but had poor reliability and reproducibility. (2) Automated count was the most expensive and least practical with major impact on turnaround time (limited by machine and personnel accessibility), and, more importantly, had inaccuracies in overcounting unwanted material. (3) Manual eye count had no additional cost, averaged 6 min, but proved impractical and poorly reproducible. (4) Camera-captured/printed image was most reliable, had highest reproducibility, but took longer than 'eye-balling'. In conclusion, based on its comparatively low cost/benefit ratio and reproducibility, camera-captured/printed image appears to be the most practical for calculating Ki67 index. Although automated counting is generally advertised as the gold standard for index calculation, in this study it was not as accurate or cost-effective as camera-captured/printed image and was highly operator-dependent. 'Eye-balling' produces highly inaccurate and unreliable results, and is not recommended for routine use.

Oxidative Balance Score and Chronic Kidney Disease.

BACKGROUND: The oxidative balance score (OBS) is a composite estimate of the overall pro- and antioxidant exposure status in an individual. The aim of this study was to determine the association between OBS and renal disease. METHODS: Using the Reasons for Geographic and Racial Differences in Stroke cohort study, OBS was calculated by combining 13 a priori-defined pro- and antioxidant factors by using baseline dietary and lifestyle assessment. OBS was divided into quartiles (Q1-Q4) with the lowest quartile, Q1 (predominance of pro-oxidants), as the reference. Multivariable logistic regression and Cox proportional hazards models were used to estimate adjusted ORs for albuminuria defined as urine albumin/creatinine ratio (ACR)>30 mg/g, macroalbuminuria defined as ACR>300 mg/g and chronic kidney disease (CKD) defined as estimated glomerular filtration rate<60 ml/min/1.73 m2 according to the Chronic Kidney Disease Epidemiology Collaboration and hazards ratios for end-stage renal disease (ESRD), respectively. RESULTS: Of the 19,461 participants analyzed, 12.9% had albuminuria and 10.1% had CKD at baseline; over a median follow-up of 3.5 years (range 2.14-4.32 years), 0.46% developed ESRD. Higher OBS quartiles were associated with lower prevalence of CKD (OR vs. Q1: Q2=0.93 [95% CI 0.80-1.08]; Q3=0.90 [95% CI 0.77-1.04] and Q4=0.79 [95% CI 0.67-0.92], p for trend<.01). The associations between OBS and albuminuria (p for trend 0.31) and incident ESRD (p for trend 0.56) were not significant in the fully adjusted models. CONCLUSIONS: These findings suggest that higher OBS is associated with lower prevalence of CKD. Lack of association with ESRD incidence in the multivariable analyses indicates that temporal relation between OBS and renal damage remains unclear.

Comparison of epidemiology, emergency care, and outcomes of acute ischemic stroke between young adults and elderly in Korean population: a multicenter observational study.

Stroke in young adults has been known to show a lower incidence and a better prognosis. Only a few studies have examined the epidemiology and outcomes of ischemic stroke in young adults and compared them with the elderly in Korean population. All consecutive patients with ischemic stroke visiting 29 participating emergency departments were enrolled from November 2007 to October 2009. Patients with less than 15 yr of age and unknown information on age and confirmed diagnosis were excluded. We categorized the patients into young adults (15 to 45 yr) and elderly (46 yr and older) groups. Of 39,156 enrolled all stroke patients, 25,818 with ischemic stroke were included and analyzed (young adult; n=1,431, 5.5%). Young adult patients showed lower prevalence of most chronic diseases but significantly higher prevalence in exercise, current smoking, and alcohol consumption. Hospital mortality was significantly lower in young adults than elderly (1.1% vs. 3.1%, P<0.001). Higher number of patients in elderly group (68.1%) showed worsening change of modified Rankin Scale than young adults (65.2%). Young adults ischemic stroke showed favorable hospital outcomes than the elderly in Korean population.