ASSOCIATIONS OF THE SERUM ALBUMIN CONCENTRATION AND SEQUENTIAL ORGAN FAILURE ASSESSMENT SCORE AT DISCHARGE WITH 1-YEAR MORTALITY IN SEPSIS SURVIVORS: A RETROSPECTIVE COHORT STUDY.

ABSTRACT: Introduction: This study was performed to investigate the predictors of 1-year mortality at discharge in sepsis survivors. Methods: This study was a retrospective analysis of patients with sepsis and septic shock at a single center. Patients who survived hospitalization for sepsis or septic shock between January 2016 and December 2017 were included in this study. Age, sex, body mass index, laboratory results such as blood cell count, C-reactive protein (CRP) and albumin levels, the Sequential Organ Failure Assessment (SOFA) score at the time of discharge and site of infection were compared between the survivors and nonsurvivors at 1 year postdischarge. Multivariate logistic regression was performed to identify the predictors of 1-year mortality. Results: During the study period, 725 sepsis patients were included in the analysis, 64 (8.8%) of whom died within the first year. The nonsurvivors were older and had a lower body mass index and a higher SOFA score at discharge than the survivors ( P < 0.05). Among the laboratory results at discharge, hemoglobin, platelet counts, and albumin concentrations were lower in the nonsurvivors than in the survivors, whereas CRP was higher in the nonsurvivors than in the survivors. In the multivariate logistic regression analysis, serum albumin <2.5 mg/dL and SOFA score ≥2 at discharge were identified as independent prognostic factors for 1-year mortality (odds ratio, 2.616; 95% confidence interval, 1.437-4.751 for albumin <2.5 mg/dL and 2.106, 1.199-3.801 for SOFA score ≥2, respectively). Conclusions: A low serum albumin concentration of <2.5 mg/dL and a high SOFA score of ≥2 at the time of discharge were prognostic factors for 1-year mortality in survivors of sepsis.

Assessment of body water distribution in patients with sepsis during fluid resuscitation using multi-frequency direct segmental bioelectrical impedance analysis.

BACKGROUND & AIMS: Although initial fluid resuscitation in sepsis is critical for the treatment of tissue hypoperfusion, little evidence supports the distribution of infused fluid in patients with sepsis. This study was designed to assess the body water distribution in patients with sepsis using bioelectrical impedance analysis and correlate the trend in body water distribution during fluid treatment with the prognosis of patients with sepsis. METHODS: A prospective study in a single emergency department was performed, and adult patients suspected of having sepsis were enrolled. Multi-frequency direct segmental bioelectrical impedance analysis (InBody S10, InBody) measuring total body water (TBW), intracellular water (ICW), and extracellular water (ECW) was applied to patients with sepsis at three periods: before, immediately after, and 1 hour after the fluid treatment. Survival data at 28 days after the fluid treatment were obtained. RESULTS: Forty-two patients were enrolled in this study. Overall, the ratios of TBW, ICW, and ECW to body weight increased throughout the fluid treatment except the ratio of ICW to body weight at 1 hour in non-survivors. While the ratio of ECW to TBW (ECW/TBW) and the ratio of ICW to TBW (ICW/TBW) in survivors remained stable over the period, the trend of ECW/TBW increased with corresponding decline of ICW/TBW in non-survivors (p = 0.0085 and p = 0.0034 between times and groups, respectively) such that ECW/TBW and ICW/TBW were significantly different at 1 hour after the fluid loading period (p = 0.0120 and p = 0.0085, respectively). This contrast pattern was equivalent with the trend of ECW/TBW in trunk but not that of the other extremities. CONCLUSIONS: During fluid resuscitation, the trend in ECW/TBW significantly increased with corresponding decrease of ICW/TBW in non-survivors compared with that in survivors, which suggests fluid resuscitation results intracellular dehydration and extracellular edema in non-survivors of patients with sepsis.

Quick Sepsis-related Organ Failure Assessment score is not sensitive enough to predict 28-day mortality in emergency department patients with sepsis: a retrospective review.

OBJECTIVE: To test the hypothesis that the quick Sepsis-related Organ Failure Assessment (qSOFA) score, derived from vital signs taken during triage and recommended by current sepsis guidelines for screening patients with infections for organ dysfunction, is not sensitive enough to predict the risk of mortality in emergency department (ED) sepsis patients. METHODS: Patients diagnosed with severe sepsis and septic shock using the old definition between May 2014 and April 2015 were retrospectively reviewed in three urban tertiary hospital EDs. The sensitivities of systemic inflammatory response syndrome (SIRS) criteria, qSOFA, and Sequential Organ Failure Assessment (SOFA) scores ≥2 were compared using McNemar's test. Diagnostic performances were evaluated using specificity, positive predictive value, and negative predictive value. RESULTS: Among the 928 patients diagnosed with severe sepsis or septic shock using the old definition, 231 (24.9%) died within 28 days. More than half of the sepsis patients (493/928, 53.1%) and more than one-third of the mortality cases (88/231, 38.1%) had a qSOFA score <2. The sensitivity of a qSOFA score ≥2 was 61.9%, which was significantly lower than the sensitivity of SIRS ≥2 (82.7%, P<0.001) and SOFA ≥2 (99.1%, P<0.001). The specificity, positive predictive value, and negative predictive value of a qSOFA score ≥2 for 28-day mortality were 58.1%, 32.9%, and 82.2%, respectively. CONCLUSION: The current clinical criteria of the qSOFA are less sensitive than the SIRS assessment and SOFA to predict 28-day mortality in ED patients with sepsis.

Arterial Stiffness by Aerobic Exercise Is Related with Aerobic Capacity, Physical Activity Energy Expenditure and Total Fat but not with Insulin Sensitivity in Obese Female Patients with Type 2 Diabetes.

BACKGROUND: Arterial stiffness is an important factor in atherosclerosis. Thus we examined whether aerobic exercise could reduce arterial stiffness in obese women with type 2 diabetes without diabetic complication. METHODS: A total of 35 women with type 2 diabetes (body mass index, 26.6±2.8 kg/m(2); age, 56.4±1.9 years; duration of diabetes, 4.7±4.8 years) were assigned to aerobic exercise group (AEG) or control group (CG). AEG completed a 12-week exercise program (3.6 to 5.2 metabolic equivalents, 3 day/week, 60 min/day), with their exercise activities monitored by accelerometers. We measured abdominal total fat area (TFA), visceral fat area (VFA), and subcutaneous fat area (SFA) by computed tomography, insulin sensitivity by insulin tolerance test (KITT), and augmentation index (AIx) by SphygmoCor at baseline and at the end of the 12-week program. RESULTS: The AIx was improved in the AEG compared with the CG (P<0.001). The percent change of AIx had significant correlation with the improvement of physical activity energy expenditure (PAEE), aerobic capacity, TFA, and SFA (r=-0.416, P=0.013; r=0.560, P<0.001; r=0.489, P=0.003; r=0.531, P=0.001, respectively), but not with insulin sensitivity, energy intake, or VFA. CONCLUSION: Improvement in aortic stiffness by aerobic exercise is related with the improvement of aerobic capacity, PAEE, and total fat but not with insulin sensitivity or energy intake in obese women with type 2 diabetes.

Quantitative assessment of DNA methylation for the detection of cervical and endometrial adenocarcinomas in liquid-based cytology specimens.

OBJECTIVE: To investigate the aberrant promoter hypermethylation as a screening tool for cervical adenocarcinomas (CAs) and endometrial adenocarcinomas (EAs) in cervical scrapings. STUDY DESIGN: A quantitative multiplex methylation-specific polymerase chain reaction approach was used to examine promoter methylation of 5 genes (APC, HIN-1, RAR-beta, RASSF1A and Twist) in biopsy-confirmed CA (n = 31) and EA (n = 27) residual, liquid-based cytology samples. The data of negative for intraepithelial lesions or malignancy and low-grade squamous intraepithelial lesions were used as controls. RESULTS: Methylation levels of APC, RAR-beta, RASSF1A and Twist were significantly higher in CA than in control cervical samples. For EA, only the methylation levels of RASSF1A differed significantly from those of control. Receiver-operating characteristic analysis demonstrated that APC, RAR-beta and RASSF1A had the ability to distinguish CA/EA, CA and EA from control samples. In CA/EA and CA samples, the best 3-gene combination was RASSF1A/RAR-beta/APC. This 3-gene panel had a sensitivity of 87.0% for CA/EA and of 80.6% for CA and a specificity of 79.3% for both CA/EA and CA. In EA samples, RASSF1A showed the best performance in distinguishing EA from control. The estimated sensitivity of RASSF1A for detecting EA was 63.0%, and its specificity was 96.3%. CONCLUSION: This feasibility study demonstrates that quantitative detection of aberrant DNA methylation in cervical scrapings may be a promising new diagnostic tool for the detection of CA and EA.

Quantitative assessment of DNA methylation for the detection of cervical neoplasia in liquid-based cytology specimens.

Previously, we have shown that methylation-specific PCR (MSP) analysis of a key panel of genes may be useful as an ancillary tool for diagnosing squamous cell carcinomas (SCC) and high-grade squamous intraepithelial lesions (HSIL) in cervical scrapings. Because quantitative MSP (QMSP) is more suitable as a screening tool than conventional MSP, we investigated the diagnostic role of QMSP for the detection of SCC and HSIL in cervical scrapings. A quantitative multiplex-MSP approach was used to examine promoter methylation of five genes (APC, HIN-1, RAR-beta, RASSF1A, and Twist) in biopsy-confirmed SCC (n = 63), HSIL (n = 45), low-grade SIL (LSIL, n = 26), and negative (n = 28) liquid-based cytology samples. For four genes (HIN-1, RAR-beta, RASSF1A, and Twist), the methylation levels among four groups were significantly different (p < 0.001 for each). Methylation levels of HIN-1, RAR-beta, RASSF1A, and Twist were increased in HSIL and SCC samples, compared with either negative or LSIL samples. However, methylation levels were not significantly different between SCC and HSIL, with the exception of RASSF1A. Receiver-operating characteristic analysis demonstrated that HIN-1, RAR-beta, RASSF1A, and Twist had the ability to distinguish HSIL/SCC from LSIL/negative samples. The two-gene combination (RASSF1A/Twist) showed the best performance in distinguishing HSIL/SCC from LSIL/negative samples. The estimated specificity of this two-gene panel for detecting HSIL/SCC was 90.7%, and its sensitivity was 74.1%. These results suggest that quantitative detection of aberrant DNA methylation in cervical scrapings may be a promising high-throughput approach for the diagnosis of HSIL/SCC.

The usefulness of an accelerometer for monitoring total energy expenditure and its clinical application for predicting body weight changes in type 2 diabetic korean women.

BACKGROUND: The purpose of this study was to evaluate the usefulness of an accelerometer in predicting body weight (BW) change during a lifestyle intervention and to find out whether exercise or overall physical activity is associated with change in insulin sensitivity and body composition. METHODS: A total of 49 overweight (body mass index [BMI] ≥ 23 kg/m(2)) women with diabetes were enrolled and performed lifestyle intervention while monitoring BW, total energy expenditure (TEE) and physical activity energy expenditure (PAEE) using an accelerometer, and energy intake (EI) using a three-day dietary record at baseline and every 2 weeks for 12 weeks. We assessed body composition using bioimpedance analysis and compared the actual BW change to the predicted BW change, which was calculated from the energy deficit (ED) between EI and TEE (ED = EI-TEE). RESULTS: Mean age was 57.2 years, duration of diabetes was 8.0 years, and BMI was 27.8 kg/m(2). There was no significant difference between EI and TEE at baseline. For 12 weeks, the ED was 474.0 kcal·day(-1), which was significantly correlated with BW change (-3.1 kg) (r = 0.725, P < 0.001). However, the actual BW change was 50% lower than the predicted BW change. Both TEE and PAEE correlated with change in K(ITT) (r = 0.334, P = 0.019; r = 0.358, P = 0.012, respectively), BMI (r = -0.395, P = 0.005; r = -0.347, P = 0.015, respectively), and fat mass (r = -0.383, P = 0.007; r = -0.395, P = 0.005, respectively), but only TEE correlated with fat free mass change (r = -0.314, P = 0.030). CONCLUSION: The accelerometer appears to be a useful tool for measuring TEE under free-living conditions for both short- and long-term periods.

Assessment of DNA methylation for the detection of cervical neoplasia in liquid-based cytology specimens.

OBJECTIVE: DNA methylation is an early event in carcinogenesis. Testing for DNA methylation has potential in cancer screening. The aim of this study was to investigate the feasibility of methylated DNA detection as a screening tool for squamous cell carcinomas (SCC) and squamous intraepithelial lesions (SIL) in cervical scrapings. METHODS: A multiplex, nested, methylation-specific polymerase chain reaction approach was used to examine promoter methylation of 12 genes (CDH1, DAPK, GSTP1, HIC-1, HIN-1, hMLH1, MGMT, p16, RAR-beta, RASSF1A, SHP-1, and Twist) in biopsy-proven SCC (n=69), high-grade SIL (HSIL, n=67), low-grade SIL (LSIL, n=32), and negative (n=41) liquid-based cytology samples. RESULTS: The methylation frequency in normal, LSIL, HSIL, and SCC was significantly different (p<0.01) for eight genes (DAPK, HIC-1, HIN-1, MGMT, RAR-beta, RASSF1A, SHP-1, and Twist). There was a trend toward increasing methylation of HIN-1, MGMT, RAR-beta, RASSF1A, and SHP-1 with increasing severity of cervical squamous lesions. The number of methylated genes increased with the severity of cervical squamous lesions (p<0.001). In receiver-operating characteristic analysis, the three-gene combination (RAR-beta/Twist/MGMT) showed the best performance to distinguish HSIL/SCC from LCIS/negative samples. The estimated specificity of this three-gene panel for detecting HSIL/SCC was 82.2%, and its sensitivity was 78.7%. CONCLUSION: Although aberrant DNA methylation has the potential to function as a molecular biomarker of HSIL and SCC in liquid-based cytology tests, additional genes that are selectively methylated in HSIL and SCC are needed to improve clinical performance.