Biomarkers of early sepsis may be correlated with outcome.

BACKGROUND: Sepsis causes high mortality, and the mortality due to secondary infections is even higher. No studies to date have investigated the time from the primary infection to death due to a secondary infection; similarly, the factors that are significantly different in sepsis survivors relative to non-survivors or in severe sepsis patients who suffered a late death relative to those who recover have not been explored. We hypothesized that patients who survive sepsis have a weaker pro-inflammatory response than those who do not and that the mid-term survivors (which acquire secondary infections) would have a pronounced anti-inflammatory response (making them susceptible to infection); this hypothesis was verified in this study. METHODS: We examined 24 patients with severe sepsis; the patients were subdivided by outcome into early death (n=5), mid-term survival (survival through severe sepsis but death within six months or continued hospitalization for six months, n=6), and long-term survival (recovery and survival for more than six months, n=13) groups. The levels of CD3+, CD4+, CD8+, and CD19+ lymphocytes were analyzed by flow cytometry, and the plasma levels of carbonic anhydrase IX (CA IX), MCP-1, IL-6, IL-7, IL-8, and IL-10 were measured by ELISA on days 0, 1, 2, and 3. A statistical comparison of the variables in the groups was conducted using a mixed model. RESULTS: The plasma levels of MCP-1, IL-6, and IL-8 in early death and survivors were significantly different, and all had p values<0.01. The plasma levels of MCP-1, IL-6, and IL-8 were also significantly different in mid-term survivors and long-term survivors, with p values of <0.01, 0.04, and <0.01, respectively. CONCLUSIONS: Our data support the hypothesis that survivors have a weaker pro-inflammatory response than non-survivors, but the mid-term survivors did not have a more pronounced anti-inflammatory response. The levels of pro-inflammatory cytokines in the mid-term and long-term survivors were significantly different.

Combining TNFSF15 and ASCA IgA can be used as a predictor for the stenosis/perforating phenotype of Crohn's disease.

BACKGROUND AND AIM: Focusing on TNFSF15 instead of NOD2, we set out to evaluate whether combining serologic and genetic markers could distinguish between Crohn's disease (CD) and ulcerative colitis (UC), and whether they could be used to stratify the disease behavior of Taiwanese CD patients. METHODS: Clinical information, serum isolation, and DNA were collected after obtaining informed consent. The serological markers were analyzed by ELISA kits and the genetic analysis for TNFSF15 single-nucleotide polymorphisms (SNPs) by Sequenom. Statistic analyses were conducted by SAS 9.2 (Cary, NC, USA). RESULTS: This study included 108 patients (55 CD, 53 UC) and 60 healthy controls. An initial low positive rate and low sensitivity for the serological markers led us to reset the cut-off values. This reset cut-off for ASCA IgA yielded a sensitivity of 0.291 and specificity of 0.925 for differentiating CD from UC patients. The reset cut-off value for p-ANCA (anti-MPO) had a sensitivity of 0.461 and a specificity of 0.817 for differentiating inflammatory bowel disease patients from healthy controls. Among the TNFSF15 SNPs, rs4263839 associated with CD in Taiwan (P = 0.005), haplotype analysis did not increase the association. Combining the genetic marker TNFSF15 (rs4263839) and serological marker ASCA IgA increased the area under the curve from 0.61 to 0.70 for predicting stenosis/perforating phenotype, compared to ASCA IgA alone. CONCLUSIONS: Serological markers need to be tested and tailored to different countries/ethnicities. Combining the genetic marker TNFSF15 with ASCA IgA increased the power of predicting stenosis/perforating phenotype in CD patients with TNFSF15 but not with a NOD2 genetic background.

The possible mediating effect of alcohol dependence on the relationship between adverse childhood experiences and attempted suicide.

Adverse childhood experiences (ACEs) and alcohol dependence (AD) carry independent risks for suicidal behavior. While the strength of the association between ACEs and attempted suicide is weakened following adjustment for AD, no study to date has directly been performed to determine whether AD affects the risk of suicide attributable to ACEs. The study aimed to examine the possible role of alcohol dependence (AD) in the relationship between various ACEs and attempted suicide. This cross-sectional study assessed history of ACEs among 184 AD patients and 205 control participants using the Family Health Questionnaire. Lifetime history of attempted suicide was collected using the Chinese version of the Composite International Diagnostic Interview. We used the Sobel test to examine the mediating effects of AD on the relationship between ACEs and attempted suicide. Results showed that the suicide attempters were associated with higher rates of AD and ACEs. The regression analysis showed that AD and multiple ACEs exposure are independently associated with attempted suicide. AD appears as a partial mediator in the relationship between attempted suicide and the specific type of ACE (exposure to a battered mother or sexual abuse) or exposure to ≥3 types of ACEs. We conclude that AD might partially mediate the associations detected between attempted suicide and exposure to a battered mother, sexual abuse, and ≥3 types of ACEs. These observations may provide important insight for intervention strategies aimed at reducing the risk of suicide attempts.

Restricted Use of Erythropoiesis-Stimulating Agent is Safe and Associated with Deferred Dialysis Initiation in Stage 5 Chronic Kidney Disease.

The effect of erythropoiesis-stimulating agent (ESA) on dialysis initiation in advanced chronic kidney disease (CKD) patients is not clear. We retrospectively analyzed the outcome of dialysis initiation in a stage 5 CKD cohort with ESA reimbursement limited to the maximal standardized monthly ESA dose equivalent to epoetin beta 20,000 U by the National Health Insurance program. Totally 423 patients were followed up for a median of 1.37 year. A time-dependent Cox regression model, adjusted for monthly levels of estimated glomerular filtration rate (eGFR) and hemoglobin, was constructed to investigate the association between ESA and outcome. The standardized monthly ESA dose in ESA users was 16,000 ± 3,900 U of epoetin beta. Annual changes of hemoglobin were -0.29 ± 2.19 and -0.99 ± 2.46 g/dL in ESA users and ESA non-users, respectively (P = 0.038). However, annual eGFR decline rates were not different between ESA users and non-users. After adjustment, ESA use was associated with deferred dialysis initiation (hazard ratio 0.63, 95% confidence interval 0.42-0.93, P = 0.021). The protective effect remained when the monthly ESA doses were incorporated. Our data showed that restricted use of ESA was safe and associated with deferred dialysis initiation in stage 5 CKD patients.

Plasma zinc alpha2-glycoprotein levels correlate positively with frailty severity in female elders.

Frailty is a geriatric syndrome associated with adiposity. Zinc alpha2-glycoprotein (ZAG), a novel adipokine, is a modulator of body fat mass and positively correlates with age. This observational study aims to investigate the relationship between plasma ZAG levels and frailty in the elderly.We enrolled 189 elder participants from a hospital-based comprehensive geriatric assessment program in Taiwan from January 2007 to June 2008. The demographic data, body weight, body mass index, appendicular skeletal muscle mass index (ASMI), body fat mass percentage, metabolic and inflammatory parameters including plasma tumor-necrosis factor alpha, C-reactive protein and ZAG levels, were assessed. The frailty score was assessed by Fried Frailty Index.The mean age of all participants (91 [48.1%] men and 98 [51.9%] women) was 77.19 ±â€Š6.12 years. Judged by the FFI score, 46 (24.34%) elders were robust, 106 (56.08%) were pre-frail, and 37 (19.58%) were frail. Older men showed greater ASMI and lower fat mass percentage in comparison to older women (P < 0.0001). The log-transformed mean plasma ZAG (µg/mL) level of overall was 1.82 ±â€Š0.11, and it was higher in men than in women (1.85 ±â€Š0.12 vs 1.79 ±â€Š0.1, P = 0.0006). Plasma ZAG levels were different among the robust, pre-frail and frail subgroups (1.78 ±â€Š0.09, 1.83 ±â€Š0.12, 1.83 ±â€Š1.10, respectively, P = 0.028), and the differences were more significant in woman elders (P = 0.005). Further multiple linear regression analysis showed plasma ZAG levels positively correlated with frailty severity in women (P for trend = 0.0435).Plasma ZAG levels positively correlated with frailty severity in woman elders. The difference between sexes suggests certain sex-specific mechanisms may exist to affect the association between plasma ZAG levels and frailty.

Fecal calprotectin correlated with endoscopic remission for Asian inflammatory bowel disease patients.

AIM: To evaluate the correlation between fecal calprotectin (fC), C-reactive protein (CRP), and endoscopic disease score in Asian inflammatory bowel disease (IBD) patients. METHODS: Stool samples were collected and assessed for calprotectin levels by Quantum Blue Calprotectin High Range Rapid test. Crohn's disease endoscopic index of severity (CDEIS) and ulcerative colitis endoscopic index of severity (UCEIS) were used for endoscopic lesion scoring. RESULTS: A total of 88 IBD patients [36 patients with Crohn's disease (CD) and 52 with ulcerative colitis (UC)] were enrolled. For CD patients, fC correlated with CDEIS (r = 0.465, P = 0.005) and CRP (r = 0.528, P = 0.001). fC levels in UC patients correlated with UCEIS (r = 0.696, P < 0.0001) and CRP (r = 0.529, P = 0.0005). Calprotectin could predict endoscopic remission (CDEIS < 6) with 50% sensitivity and 100% specificity (AUC: 0.74) in CD patients when using 918 µg/g as the cut-off. When using 191 µg/g as the cut-off in UC patients, calprotectin could be used for predicting endoscopic remission (UCEIS < 3) with 88% sensitivity and 75% specificity (AUC: 0.87). CONCLUSION: fC correlated with both CDEIS and UCEIS. fC could be used as a predictor of endoscopic remission for Asian IBD patients.

Clinicopathologic features and responses to radiotherapy of myeloid sarcoma.

BACKGROUND: To evaluate clinicopathological features, radiotherapeutic parameters, and their associations with responses to radiotherapy (RT) in patients with myeloid sarcoma (MS). METHODS: We reviewed 20 patients receiving RT for MS lesions (in 43 RT courses) and analyzed the patients' clinicopathologic features and radiotherapeutic parameters, and their associations with complete responses (CR) to RT using Fisher's exact test and univariate logistic regression analysis. Generalized Estimating Equation was used to analyze all 43 irradiated lesions and account for the correlations in RT responses among lesions from the same patient. RESULTS: We found that the underlying hematological diseases of the evaluated patients were acute myeloid leukemia (AML) in 14 patients (70%), chronic myeloid leukemia in 4 patients (20%), myelodysplastic syndrome with AML transformation in one patient (5%), and de novo MS in one patient (5%). Most patients (55%) received RT for MS at the time of relapse following bone marrow transplantation (BMT). The most common cytogenetic abnormality was t(8;21)(q22;q22). The median RT dose of 20 Gy (range 6-35 Gy), administered in 1.5-3.5 Gy fractions, provided a 63% CR rate. RT dose, sex, cytogenetics, and bone marrow status at the time of RT had no significant effect on CR. Younger age (<50 y, P = 0.06), BMT prior to RT (P = 0.05), and underlying AML (P = 0.05) were marginally associated with higher CR to RT. CONCLUSIONS: Our results indicate that a modest RT dose (20-30 Gy) achieves good local control of MS. Age, previous BMT, and underlying hematologic disease can affect RT response.