Inverse Association of Serum Adipsin with the Remission of Nonalcoholic Fatty-Liver Disease: A 3-Year Community-Based Cohort Study

<b><i>Purposes:</i></b> Adipokine alterations contribute to the development and remission of nonalcoholic fatty-liver disease (NAFLD). Adipsin is one of the most abundant adipokines and is almost exclusively produced by adipocytes. However, data on adipsin in human NAFLD are limited and controversial. We performed this study to investigate the association between adipsin and the remission of NAFLD in middle-aged and elderly Chinese adults. <b><i>Methods:</i></b> Whether adipsin is associated with the remission of NAFLD in a 3-year community-based prospective cohort study was investigated. Baseline levels of adipsin were measured in serum samples collected from 908 NAFLD participants. NAFLD was diagnosed using abdominal ultrasonography. Logistic regression analysis and a multiple stepwise logistic regression model including different variables were conducted to evaluate the association between serum adipsin levels and the remission of NAFLD. <b><i>Results:</i></b> During a mean follow-up of 3.14 ± 0.36 years, 247 (27.20%) participants with NAFLD at baseline were in remission. At baseline, serum adipsin concentration was positively correlated with body mass index (<i>r</i>: 0.39, <i>p</i> &#x3c; 0.001), insulin (<i>r</i>: 0.31, <i>p</i> &#x3c; 0.001), and homeostasis model assessment of insulin resistance (<i>r</i>: 0.31, <i>p</i> &#x3c; 0.001) and was inversely associated with NAFLD remission with a fully adjusted odds ratio (OR) of 0.28 (0.16–0.48) (<i>p</i> trend &#x3c; 0.001). In a multiple stepwise logistic regression model, circulating adipsin independently predicted NAFLD remission (OR: 0.284, 95% confidence interval [CI]: 0.172–0.471, <i>p</i> for trend &#x3c;0.001). The area under the receiver operating characteristic curve was 0.751 (95% CI: 0.717–0.785) (<i>p</i> &#x3c; 0.001) for the prediction model of NAFLD remission. <b><i>Conclusions:</i></b> We provide evidence for an association between serum adipsin levels and the remission of NAFLD in a community-based prospective cohort study. Serum adipsin can be a potential biomarker for predicting NAFLD remission.

TMA-93 Validation by Alzheimer’s Disease Biomarkers: A Comparison with the Free and Cued Selective Reminding Test on a Biobank Sample

Background: The Memory Associative Test TMA-93 examines visual relational binding, characteristically affected in early-AD stages. Objective: We aim to validate the TMA-93 by biomarkers determination and compare its diagnostic characteristics with the Free and Cued Selective Reminding Test (FCSRT). Methods: Retrospective analysis of a Biobank database. Patients’ records initially consulted for memory complaints, scored MMSE≥22, had TMA-93 and FCSRT tested, and AD biomarker determination (Amyloid-PET or CSF), either positive or negative, were selected. As cutoffs, we considered the 10-percentile for TMA-93 (P10/TMA-93), and “total free recall” (TFR) 21/22, total recall (TR) 43/44, and Cued Index < 0.77 for FCSRT from previous Spanish validation and normative studies. Diagnostic utilities were calculated using ROC curves and compared by the DeLong method. We studied if one test improved the other test’s prediction, following a forward stepwise logistic regression model. Results: We selected 105 records: 64 “positive” and 41 “negative” biomarkers. TMA-93 total score diagnostic utility (AUC = 0.72; 95%CI:0.62–0.82) was higher than those of the FCSRT: TFR (AUC = 0.70; 95%CI: 0.60–0.80), TR (AUC = 0.63; 95%CI:0.53–0.74), and Cued Index (AUC = 0.62; 95%CI:0.52–0.73). The P10/TMA-93 cutoff showed 86%sensitivity, similar to that of the most sensitive FCSRT cutoff (TFR21/22, 89%) and 29%specificity, lower than that of the most specific FCSRT cutoff (Cued Index < 0.77, 57%). 32.8%of the positive-biomarker group scored above CI/0.77 but below p10TMA-93. The addition of TMA-93 total score to FCSRT variables improved significantly the biomarkers results’ prediction. Conclusion: TMA-93 demonstrated “reasonable” diagnostic utility, similar to FCSRT, for discriminating AD biomarker groups. TMA-93 total score improved the AD biomarker result prediction when added to FCSRT variables.

A machine learning-based prediction of hospital mortality in patients with postoperative sepsis

Background: The incidence of postoperative sepsis is continually increased, while few studies have specifically focused on the risk factors and clinical outcomes associated with the development of sepsis after surgical procedures. The present study aimed to develop a mathematical model for predicting the in-hospital mortality among patients with postoperative sepsis.Methods: Surgical patients in Medical Information Mart for Intensive Care (MIMIC-III) database who simultaneously fulfilled Sepsis 3.0 as well as Agency for Healthcare Research and Quality (AHRQ) criteria during ICU admission were incorporated. We employed both extreme gradient boosting (XGBoost) and stepwise logistic regression model to predict in-hospital mortality among included patients with postoperative sepsis. Consequently, model performance was assessed from the angles of discrimination and calibration.Results: We included 3713 patients who fulfilled our inclusion criteria, in which 397 (10.7%) patients died during hospitalization, while 3316 (89.3%) of them survived through discharge. Fluid-electrolyte disturbance, coagulopathy, renal replacement therapy (RRT), urine output, and cardiovascular surgery were important features related to the in-hospital mortality. The XGBoost model had a better performance in both discriminatory ability (c-statistics, 0.835 [95% CI, 0.786 to 0.877] vs. c-statistics, 0.737 [95% CI, 0.688 to 0.786]) and goodness of fit (visualized by calibration curve) compared to the stepwise logistic regression model. Conclusion: XGBoost model appears to be a better performance in predicting hospital mortality among postoperative septic patients compared to the conventional stepwise logistic regression model. Machine learning-based algorithm might have significant application in the development of early warning system for septic patients following major operations.

Early progression (progr) in patients (pts) with metastatic pancreatic cancer (mPaC) and a germline BRCA mutation (gBRCAm): Phase III POLO trial of olaparib (O) versus placebo (P).

750 Background: In POLO (NCT02184195), maintenance O was associated with significant progr-free survival benefit vs P in pts with a gBRCAm and mPaC (Golan NEJM 2019). Early progr or death (within 4 months [m]) occurs in ~35−45% of pts on standard-of-care first-line (1L) chemotherapy for mPaC (Conroy NEJM 2011; von Hoff NEJM 2013); however, predictive factors are currently unknown and early progr has not been addressed in the maintenance setting. We examined factors potentially associated with early progr in POLO. Methods: Following ≥16 weeks of 1L platinum-based chemotherapy (PBC) without progr, pts were randomized to maintenance O (tablets; 300 mg bd) or P until progr or unacceptable toxicity. Early progr was defined as progr (by blinded independent central review) or death within 4 m of randomization. A stepwise logistic regression model included baseline (BL) factors age, albumin, lactate dehydrogenase (LDH), global health status (GHS) and physical functioning (PhysF) as continuous variables, and discrete variables listed in the Table. Results: 62/154 randomized pts (40%) were defined as early progressors (EP; Table). Due to missing BL data, the multivariate analysis included 127 pts (56 EPs [44%]). Lower BL PhysF score (continuous) was significantly associated with early progr ( P= 0.02); no difference for partial/complete response (PR/CR) vs stable disease (SD). Conclusions: While small sample size limited analysis power, PhysF score was the only BL factor significantly associated with early progr in pts with a gBRCAm and mPaC in the POLO trial of maintenance O vs P. Clinical trial information: NCT02184195 . [Table: see text]

Adherence to ready-to-use food and acceptability of outpatient nutritional therapy in HIV-infected undernourished Senegalese adolescents: research-based recommendations for routine care.

Background: Ready-to-use food (RUF) is increasingly used for nutritional therapy in HIV-infected individuals. However, practical guidance advising nutrition care to HIV-infected adolescents is lacking, and little is known about the acceptability of such therapy in this vulnerable population. This SNACS study assesses the overall acceptability and perception of a RUF-based therapy and risk factors associated with sub-optimal RUF intake in HIV-infected undernourished adolescents in Senegal. Methods: Participants aged 5 to 18 with acute malnutrition were enrolled in 12 HIV clinics in Senegal. Participants were provided with imported RUF, according to WHO prescription weight- and age-bands (2009), until recovery or for a maximum of 9-12 months. Malnutrition and recovery were defined according to WHO growth standards. Adherence was assessed fortnightly by self-reported RUF intake over the period. Sub-optimal RUF intake was defined as when consumption of the RUF provision was < 50%. RUF therapy acceptability and perceptions were assessed using a structured questionnaire (week 2) and focus group discussions (end of the study). Factors associated with sub-optimal RUF intake at week 2 were identified using stepwise logistic regression model. Results: We enrolled 173 participants, with a median age of 12.5 years (Interquartile range: 9.5 – 14.9), of whom 61% recovered from malnutrition within the study period. Median follow-up duration was 66 days (21 – 224). At week 2, sub-optimal RUF intake was observed in 31% of participants. Dislike of the taste of RUF (aOR=5.0, 95% CI: 2.0 – 12.3), HIV non-disclosure (5.1, 1.9 – 13.9) and food insecurity (2.8, 1.1 – 7.2) were the major risk factors associated with sub-optimal RUF intake. Most participants initially reported a positive organoleptic appreciation of RUF. Constraints on RUF feeding were the need to hide from others to avoid sharing and limited time available. Among sub-optimal consumers, disgust and adverse effects attributed to RUF were perceived as barriers impossible to overcome. Conclusions: This study revealed several factors reducing the acceptability and adherence to RUF therapy based on WHO guidelines in HIV-infected adolescents. Strengthening counselling capacity of HIV clinics, tailoring prescriptions and empowering young patients, are crucial for improving acceptability of RUF-based therapy in routine care.

α-1-Acid Glycoprotein Concentration as an Outcome Predictor in Adult Patients with Sepsis

Background. α-1-Acid glycoprotein (AGP) is an acute-phase protein that plays a role in first-line defense against infection and is therefore elevated in sepsis. We tested the hypothesis that AGP levels increase initially in sepsis and decrease after antimicrobial therapy and that these levels may predict treatment outcomes. Methods. AGP, biomarkers widely used in clinical practice, and maximum 24-h acute physiology and chronic health evaluation (APACHE)-II scores upon emergency department (ED) admission were prospectively evaluated and compared. We further examined changes in AGP concentrations 1, 4, and 7 days after admission and determined the value of AGP that may be used to accurately and reliably predict the prognosis in patients with sepsis. Results. Mechanical ventilation, white blood cell (WBC) counts, C-reactive protein (CRP) and lactate levels, maximum 24-h APACHE-II scores, and AGP concentrations were significantly higher upon admission in patients with sepsis who died. AGP and lactate concentrations were also significantly higher in non-survivors than in survivors on days 1, 4, and 7. As indicated by the stepwise logistic regression model analysis and area under the curve analysis, AGP was the best prognostic indicator, and the cut-off value for predicting fatality was 1307 μg/mL, and any increase 1-ng/mL in AGP concentration would increase the fatality rate by 0.5%. Conclusion. Based on our observations, AGP may be a good prognostic predictor in patients with sepsis. In addition, serial AGP levels meet the requirements for predicting outcomes in patients with sepsis.

Impact of Vancomycin-Associated Acute Kidney Injury on Patient Outcomes in MRSA Bacteremia

Background Acute kidney injury (AKI) is a well-known adverse effect of vancomycin. Varying degrees and causes of AKI have demonstrated different effects on patient outcomes. Since AKI with vancomycin is typically reversible, we investigated how AKI associated with vancomycin therapy impacts patient mortality and time to discharge. Methods Unique patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and who received at least one dose of vancomycin were identified in a national Veterans Affairs cohort from January 1, 2002 to October 14, 2015. Patients with a history of dialysis in the previous year and those with AKI on admission were excluded. AKI was defined according to RIFLE criteria, as an increase in serum creatinine (SCr) of 0.5 mg/dL or 1.5× from the admission SCr, on a day they received vancomycin. Patient characteristics including demographics and comorbidities defined by ICD9 codes were compared between groups. Effect estimates for inpatient mortality were determined with a backward stepwise logistic regression model in SAS 9.2. For patients without inpatient mortality, time to discharge was analyzed using Wilcoxon rank-sum test. Results There were 7691 included patients with MRSA bacteremia, and 23.8%&#x2028;(n = 1830) developed AKI during therapy. Mean age was 66.7 (±12) years and 97.8% (n = 7525) were male. Patients with AKI were more likely to have congestive heart failure, diabetes, chronic kidney disease, and to be admitted to the intensive care unit (all P &lt; 0.001). Overall inpatient mortality was 17.7% (n = 1361). The crude odds of inpatient mortality were 67% higher in patients with AKI. In the adjusted model, AKI was an independent predictor of mortality (OR 1.19, 95% CI 1.02–1.40, P &lt; 0.03). Median (IQR) time to discharge was 11 (6–19) days without AKI and 18 (11–31) days with AKI (P &lt; 0.0001). Conclusion Vancomycin-associated AKI is associated with increased inpatient mortality and longer time to discharge. Further research is needed to compare clinical outcomes for other groups of patients, and to determine the impact of monitoring interventions to improve safety and decrease AKI. Disclosures A. Caffrey, Merck: Grant Investigator, Grant recipient The Medicines Company: Grant Investigator, Grant recipient Pfizer: Grant Investigator, Grant recipient K. LaPlante, Merck: Grant Investigator, Grant recipient Pfizer: Grant Investigator, Grant recipient Cempra: Scientific Advisor, Consulting fee The Medicines Company: Grant Investigator, Grant recipient Allergan: Scientific Advisor, Consulting fee Bard/ Davol: Scientific Advisor, Consulting fee Ocean Spray: Grant Investigator and Scientific Advisor, Consulting fee and Grant recipient Zavante: Scientific Advisor, Consulting fee Achaogen: Scientific Advisor, Consulting fee

Selenium status in UK pregnant women and its relationship with hypertensive conditions of pregnancy

Dietary intake/status of the trace mineral Se may affect the risk of developing hypertensive conditions of pregnancy, i.e. pre-eclampsia and pregnancy-induced hypertension (PE/PIH). In the present study, we evaluated Se status in UK pregnant women to establish whether pre-pregnant Se status or Se supplementation affected the risk of developing PE/PIH. The samples originated from the SPRINT (Selenium in PRegnancy INTervention) study that randomised 230 UK primiparous women to treatment with Se (60 μg/d) or placebo from 12 weeks of gestation. Whole-blood Se concentration was measured at 12 and 35 weeks, toenail Se concentration at 16 weeks, plasma selenoprotein P (SEPP1) concentration at 35 weeks and plasma glutathione peroxidase (GPx3) activity at 12, 20 and 35 weeks. Demographic data were collected at baseline. Participants completed a FFQ. UK pregnant women had whole-blood Se concentration lower than the mid-range of other populations, toenail Se concentration considerably lower than US women, GPx3 activity considerably lower than US and Australian pregnant women, and low baseline SEPP1 concentration (median 3·00, range 0·90–5·80 mg/l). Maternal age, education and social class were positively associated with Se status. After adjustment, whole-blood Se concentration was higher in women consuming Brazil nuts (P= 0·040) and in those consuming more than two seafood portions per week (P= 0·054). A stepwise logistic regression model revealed that among the Se-related risk factors, only toenail Se (OR 0·38, 95 % CI 0·17, 0·87,P= 0·021) significantly affected the OR for PE/PIH. On excluding non-compliers with Se treatment, Se supplementation also significantly reduced the OR for PE/PIH (OR 0·30, 95 % CI 0·09, 1·00,P= 0·049). In conclusion, UK women have low Se status that increases their risk of developing PE/PIH. Therefore, UK women of childbearing age need to improve their Se status.

The Role of Soil and Landscape Factors in Chinese Privet (Ligustrum sinense) Invasion in the Appalachian Piedmont

There is a limited understanding about the ecological mechanisms that enable certain plant species to become successful invaders of natural areas. This study was conducted to determine the soil and landscape characteristics that correlate with invasion of Chinese privet (CHP), and to develop a model to predict the probability of CHP invasion in Piedmont forests. A landscape ecosystem classification (LEC) system—based on the percentage of clay in the B horizon, depth to maximum clay (cm), exposure, terrain shape, and aspect (degrees)—was used to determine the soil moisture characteristics of invaded and uninvaded plots. Additional measurements included the cover classes of CHP and other species, litter depth (cm), slope (degrees), overstory basal area (m2 ha−1), and soil chemical properties. CHP invasion was negatively correlated with overstory basal area and slope and positively with litter depth and pH. A stepwise logistic regression model containing these four variables was highly sensitive, with an overall accuracy of 78%. Given the accuracy of this model, we propose that it can be used to calculate the probability of invasion in a given area, provided that some basic, readily obtainable site characteristics are known.

Prevalence and Incidence of Syphilis among Volunteer Blood Donors in Israel

Data of 1,290,222 volunteer blood donors, in a 5-year period, was analyzed for prevalence and incidence of syphilis. Subsequent testing of donations positive in Treponema pallidum hemagglutination assay included Venereal Disease Research Laboratory and fluorescent Treponemal antibody absorption. Stepwise logistic regression model was used to identify positive syphilis serology. Prevalence of syphilis was 47 : 100,000, similar in men and women and increased significantly with age (P<0.001). Native Israelis had the lowest prevalence rate of syphilis (21 : 100,000), while a significantly higher prevalence was found among immigrants from Africa, Eastern Europe, and South America (odds ratios of 19.0, 10.8, and 7.3, resp., P<0.001 for each). About 33.2% of the seropositive donors had evidence of recent infection, and 66.8% had past infections. Incidence rate reached 8 : 100,000 person-years. Coinfection with HIV, HCV, and HBV was calculated as 8%, 1.88%, and 0.37% for positive donations, respectively. The data support the need to continue screening blood donors in Israel for syphilis and employ preventive measures to populations at risk, in order to improve public health, blood safety, and quality. A subsequent study to assess blood donors’ knowledge, attitude, and behavior is planned. In times of global migration this information may be useful to blood services worldwide.