Serum levels of copeptin predict adverse outcomes and improve risk prediction of TRISS and MGAP scores in patients with multiple trauma: A single-center prospective cohort study.

BACKGROUND: Multiple trauma deserves early prognostication and stratification. Copeptin, a precursor of vasopressin, is produced in response to stress. We examined the association between serum levels of copeptin and mortality risk in patients with multiple trauma. We aimed to also enhance the previously established Trauma-Related Injury Severity Score (TRISS) and Mechanism, GCS, Age, and Arterial Pressure (MGAP) score with the additional consideration of copeptin levels. METHODS: This single-center prospective cohort study enrolled patients who presented to the emergency department with potential major injuries. The serum levels of copeptin were measured, and the correlation to clinical severity in terms of 30-day mortality and requirement of intensive care management was analyzed. By combining copeptin levels with TRISS or MGAP, comparison between performance of the original models with the copeptin-enhanced models was performed via discrimination, calibration, and reclassification analyses. RESULTS: There was a significant increase in copeptin levels in patients who died within 30 days (median 644.4 pg/L, interquartile range [472.5, 785.9]) or were admitted to intensive care units (233.8 pg/L, [105.7, 366.4]), compared with those who survived (37.49 pg/L, [17.88, 77.68]). Adding the natural log of copeptin levels to the established TRISS and MGAP models improved the AUC of TRISS from 0.89 to 0.96, and that of MGAP from 0.82 to 0.95. Both calibrations as measured by Brier's scores and reclassification as measured by net reclassification improvement or integrated discrimination improvement demonstrated significant improvements. A Web-based calculator was built to generate predicted mortality rates of various models for convenient clinical use. CONCLUSION: Admission serum copeptin levels were correlated with clinical severity in multiple trauma. Coupling copeptin with preexisting trauma severity scores improved prediction accuracy. Copeptin shows promise as a novel biomarker for the prediction of trauma outcome. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level III.

Different cutoffs of hypertension, risk of incident diabetes and progression of insulin resistance: A prospective cohort study.

BACKGROUND/PURPOSE: Hypertension is a risk factor of incident diabetes. In 2017, the ACC/AHA updated the definition of hypertension to above 130/80 mmHg, while the 2018 ESC/ESH guideline and the JNC7 criteria remained the cutoff of 140/90 mmHg. This study was aimed to investigate how different cutoffs of hypertension affect the association of hypertension to incident diabetes and the progression of insulin resistance. METHODS: A total of 1177 subjects without diabetes at baseline were followed for 4.5 years. Diabetes was diagnosed by the results of oral glucose tolerance tests and hemoglobin A1c, or if anti-diabetic agents were used. RESULTS: Hypertension by both criteria was associated with incident diabetes. Change of HOMA2-IR every 5 years (ΔHOMA2-IR/5 yr) was higher in subjects with hypertension than those without (adjusted p = 0.044). Subjects with treated hypertension had the highest risk of diabetes (HR 2.98, p < 0.001) and ΔHOMA2-IR/5 yr, compared with subjects with normal blood pressure. However, the associations of hypertension, HR of incident diabetes and ΔHOMA2-IR/5 yr were attenuated by the 2017 ACC/AHA criteria, as compared with that by the JNC7 and 2018 ESC/ESH criteria. CONCLUSION: Hypertension by both criteria is associated with incident diabetes and accelerated progression of insulin resistance, and the associations are attenuated by the 2017 ACC/AHA criteria.

Temporal Trends in the Microbiological Characteristics of Sepsis in the United States: A Population Based Study.

BACKGROUND: Epidemiologic studies are needed for monitoring population-level trends in sepsis. This study examines sepsis-causing microorganisms from 2006 to 2014 in the United States using data from the Nationwide Inpatient Sample database. METHODS: 7 860 686 adults hospitalized with sepsis were identified using a validated ICD-9 coding approach. Associated microorganisms were identified by ICD-9 code and classified by major groups (Gram-positive, Gram-negative, fungi, anaerobes) and specific species for analysis of their incidence and mortality. RESULTS: The rate of sepsis incidence has increased for all four major categories of pathogens, while the mortality rate decreased. In 2014, Gram-negative pathogens had a higher incidence than Gram-positives. Anaerobes increased the fastest with an average annual increase of 20.17% (p < 0.001). Fungi had the highest mortality (19.28%) and the slowest annual decrease of mortality (-2.31%, p = 0.006) in 2013, while anaerobic sepsis had the highest hazard of mortality (adjusted HR 1.60, 95% CI 1.53-1.66). CONCLUSIONS: Gram-negative pathogens have replaced Gram-positives as the leading cause of sepsis in the United States in 2014 during the study period (2006-2014). The incidence of anaerobic sepsis has an annual increase of 20%, while the mortality of fungal sepsis has not decreased at the same rate as other microorganisms. These findings should inform the diagnosis and management of septic patients, as well as the implementation of public health programs.

Progression of insulin resistance: A link between risk factors and the incidence of diabetes.

AIMS: Insulin resistance (IR) changes over time during the development of type 2 diabetes. Some reports showed that obesity was associated with progression of IR. However, no study has explored if change of IR predicts incident diabetes, and no study has investigated other factors associated with the change. METHODS: In this study, 1184 subjects without diabetes at baseline were enrolled in 2006-2016 with a median follow-up period of 4.5 years. Diabetes was diagnosed by oral glucose tolerance test and hemoglobin A1c, or if anti-diabetic agents were used. HOMA2-IR and ISI0,120 were used to estimate IR. RESULTS: The annual changes of HOMA2-IR(ΔHOMA2-IR/year) and ISI0,120(ΔISI0,120/year) were associated with BMI, waist circumference(WC), glucose, HbA1c, triglyceride and HDL-cholesterol. Subjects with pre-diabetes or metabolic syndrome were associated with a more rapid increase of IR. ΔHOMA2-IR/year and ΔISI0,120/year were correlated with annual changes of BMI and WC. The hazard ratios for ΔHOMA2-IR/year and ΔISI0,120/year to predict incident diabetes were 1.39 (95% CI 1.22-1.59, p < 0.001) and 0.13 (95% CI 0.09-0.19, p < 0.001) in adjusted models, respectively. CONCLUSIONS: Change of IR can be used as a surrogate marker of incident diabetes. The progression of IR is an important pathophysiologic link between risk factors and the incidence of diabetes.

Clinical predictors and outcome impact of community-onset polymicrobial bloodstream infection.

OBJECTIVES: Very few studies have characterised community-onset polymicrobial bloodstream infections (BSIs). This study determined the incidence, risk factors, and outcomes of polymicrobial BSI as compared with monomicrobial BSI in a cohort of patients with community-onset BSIs. METHODS: This prospective cohort study enrolled consecutive patients with laboratory confirmed BSIs who were admitted to two tertiary emergency departments in Taiwan between 1 January 2015 and 31 December 2016. It assessed the independent impact of polymicrobial BSIs on survival by a propensity score weighting method. Subsequently, independent clinical predictors were identified with multivariate logistic regression model analysis with internal validation by 10-fold cross validation. RESULTS: Among 1166 patients with community-onset BSI, 133 (10.9%) episodes of polymicrobial BSIs occurred. Anaerobe, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Enterococcus spp., and Candida spp. were the most common isolated microorganisms in polymicrobial BSI. Polymicrobial BSIs were associated with an increased 90-day mortality rate (OR 2.20, 95% CI 1.98-2.60). A prediction model was built to predict polymicrobial BSI with moderate predictability (c statistic = 0.78). Significant predictors included biliary tract infection, nosocomial infection, nursing home residence, stroke, and afebrile presentation. CONCLUSIONS: Polymicrobial BSI occurred in approximately 1 in 10 episodes of community-onset BSI and was independently associated with excess mortality. Clinical predictors identified in this study may help guide the prescription of empiric broad-spectrum antibiotics.

Combining procalcitonin with the qSOFA and sepsis mortality prediction.

To investigate whether procalcitonin (PCT) can improve the performance of quick sequential organ failure assessment (SOFA) score in predicting sepsis mortality, we conducted a retrospective multicenter cohort study with independent validation in a prospectively collected cohort in 3 tertiary medical centers. Patients with presumed sepsis were included. Serum PCT levels were measured at admission. Quick SOFA score and systemic inflammatory response syndrome (SIRS) criteria were calculated for each patient. PCT levels were assigned into 0, 1, and 2 points for a serum level of <0.25, 0.25 to 2, and >2 ng/mL, and added to the quick sepsis-related organ failure assessment (qSOFA) score. The incremental value of PCT to qSOFA was then evaluated by logistic regression, receiver-operating characteristic (ROC) curve, and reclassification analysis.In all, 1318 patients with presumed severe infection were enrolled with a 30-day mortality of 13.5%. Serum level of PCT showed a high correlation with qSOFA score and 30-day inhospital mortality. The area under the ROC curve was 0.56 for SIRS criteria, 0.67 for qSOFA score, and 0.73 for qSOFA_PCT in predicting 30-day mortality. The risk prediction improvement was reflected by a net reclassification improvement of 35% (17%-52%). Incorporation of PCT into the qSOFA model could raise the sensitivity to 86.5% (95% confidence interval 80.6%-91.2%). In the validation cohort, qSOFA_PCT greatly improved the sensitivity to 90.9%.A simple modification of qSOFA score by adding the ordinal scale of PCT value to qSOFA could greatly improve the suboptimal sensitivity problem of qSOFA and may serve as a quick screening tool for early identification of sepsis.

Increased heterogeneity of brain perfusion is an early marker of central nervous system involvement in antiphospholipid antibody carriers.

OBJECTIVE: The non-criteria neuropsychiatric manifestations of antiphospholipid syndrome include headache, dizziness, vertigo, seizure, depression and psychosis. There were still no objective methods qualified to detect the early central nervous system involvement in non-criteria antiphospholipid syndrome. We evaluated the effectiveness of Tc-99m ECD SPECT in assessing circulatory insufficiency in the brains of patients with antiphospholipid antibodies and neuropsychiatric symptoms but without thromboembolism. MATERIALS AND METHODS: Patients with a history of positive antiphospholipid antibodies and neuropsychiatric symptoms composed the case group; patients without antiphospholipid antibody served as the control group. Subjects with a history of thromboembolism or autoantibodies to extractable nuclear antigens were excluded. All patients received Tc-99m ECD SPECT studies and were classified by the number of positive antiphospholipid antibodies they carried. The heterogeneity of brain perfusion was defined as the coefficient of variation of the SPECT signals. Analysis of variance (ANOVA) was applied to evaluate the differences between the groups. RESULTS: Total 60 adult patients were included in this study. There were 54 patients in the case group and 6 patients in the control group. The mean age was 38.3 ± 11.5 years. There were 52 women and 8 men. There was no significant difference in the mean brain perfusion between groups (P = 0.69). However, Tc-99m ECD SPECT demonstrated significant heterogeneity of brain perfusion in relation to the number of antiphospholipid antibodies (P = 0.01). CONCLUSIONS: This is the first study demonstrating that Tc-99m ECD SPECT can early detect the increased heterogeneity of brain circulation in non-criteria antiphospholipid antibody carriers.

The Impact of Gastric Atrophy on the Incidence of Diabetes.

Gastric atrophy results in lower plasma ghrelin, higher gastrin secretion, a change in gut microbiota, and altered dietary nutrient absorption, which may be associated with the incidence of diabetes. Helicobacter pylori (H. pylori) infection is a major cause of gastric atrophy and is associated with diabetes in some reports. Since there is no study which investigates the impact of gastric atrophy on diabetes, we conduct a prospective cohort study to examine the relationship between H. pylori infection, gastric atrophy, and incident diabetes. In this study, subjects with gastric atrophy had a lower risk of incident diabetes, compared to those without gastric atrophy. The extent of gastric atrophy, measured by serum pepsinogen (PG) I/II ratio, was correlated with age, H. pylori IgG titer, HOMA2-IR, and HOMA2%B. When gastric atrophy is more extensive, presented as a lower serum PG I/II ratio, the risk of incident diabetes is lower. On the other hand, there was no significant association between H. pylori infection and the incidence of diabetes. In conclusion, the presence and the extent of gastric atrophy, but not H. pylori infection, are associated with incident diabetes. Further studies are needed to investigate the detailed mechanisms and the potential applications of the findings to guide diabetes screening and treatment strategies.

Risk factors and outcomes of afebrile bacteremia patients in an emergency department.

OBJECTIVE: There is limited research on afebrile bacteremia. We aimed to compare the risk factors and outcomes of patients with afebrile and febrile infections. METHODS: This was a retrospective cohort study of bloodstream isolates from 994 adults admitted to the emergency department of a university hospital. Afebrile infections, defined as the absence of fever history or measured fever through the emergency department course, was compared with febrile infection. Frequencies and proportions of sources of infection, comorbidities, along with organ failure and mortality were presented. The major outcome measure was 30-day survival. chi-Square or Student's t test was used for univariate analysis, and Cox proportional hazard model was used for multivariate analysis. RESULTS: We found that the risk factors and outcomes of febrile and afebrile bacteremia patients were very different. The afebrile patients were older, have higher Charlson comorbidity index, and had poorer outcomes than the febrile patients. We also found that oldest old age, nonhematologic malignancy, necrotizing fasciitis, spontaneous bacterial peritonitis, and pneumonia were each positive independent predictors of afebrile bacteremia, whereas Escherichia coli infection and liver abscess were independent negative predictors of afebrile bacteremia. Finally, the 30-day all-cause mortality was higher in the afebrile group than in the febrile group (45% versus 12%, log-rank P<0.001). CONCLUSIONS: This series of patients with afebrile bacteremia confirmed the previously reported associations with old age and immunocompromised conditions. Clinicians should explore the possibility of occult severe infection, and initiate early hemodynamic support and empirical antimicrobial therapy for patients with the aforementioned risk factors.

The value of losartan suppression test in the confirmatory diagnosis of primary aldosteronism in patients over 50 years old.

OBJECTIVE: The diagnosis of primary aldosteronism (PA) among the older-aged population has posed a crucial challenge. Among patients over 50 years old, this trial assessed comparability of the performance of two PA diagnostic tests: losartan and captopril suppression tests. METHODS: A post-hoc subgroup analysis from a prospective cohort was conducted by the TAIPAI (Taiwan Primary Aldosteronism Investigation) group between July 2003 and July 2006. Of the 160 patients in the cohort, 60 patients over 50 years old received captopril and losartan tests to confirm PA. RESULTS: Among the 60 patients over 50 years old, 31 patients had PA confirmed by standardized protocol. The area under the receiver-operating characteristic (ROC) curve for post-captopril aldosterone was significantly less than that for post-losartan plasma aldosterone concentration (PAC) (0.87 vs 0.94, p=0.02). Using the aldosterone-renin ratio (ARR)>35 with PAC>10 ng/dl, the specificity was 82.76% vs 93.1% and the sensitivity was 77.42% vs 87.10% for the captopril and losartan tests, respectively. The equivalence between the two tests were confirmed by the exact McNemar's test (p=1.0). CONCLUSION: The losartan test showed comparable accuracy to confirm PA. Verification of this "elderly-friendly" confirmatory test will be the first step to prepare a specific diagnostic model of PA for the older-aged population.

Measurement of Waist Circumference: midabdominal or iliac crest?

OBJECTIVE: Waist circumference (WC) is used to define central obesity. This study aimed to compare the performance of two recommended locations of WC measurement. RESEARCH DESIGN AND METHODS: A cohort of 1,898 subjects who were without diabetes from 2006 to 2012 were followed for a median of 31 months (Taiwan Lifestyle Study). The WC-IC, recommended by the National Cholesterol Education Program Third Adult Treatment Panel, was measured at the superior border of the iliac crest, and the WC-mid, recommended by World Health Organization and International Diabetes Federation, was measured midway between the lowest ribs and the iliac crest. The abdominal subcutaneous fat area (SFA) and visceral fat area (VFA) were assessed by computed tomography. RESULTS: There was greater difference between WC-IC and WC-mid measurements in women than in men (P < 0.001). Both WC-IC and WC-mid correlated significantly with BMI, VFA, and SFA (all P < 0.001). WC-mid was better correlated to VFA than WC-IC, particularly in women, and it correlated more strongly to blood pressure, plasma glucose, hemoglobin A1c, triglyceride levels, HDL cholesterol, and C-reactive protein (all P < 0.05). The association of WC-mid with hypertension, diabetes, and metabolic syndrome was slightly better than that of WC-IC (area under the receiver operator curve 0.7 vs. 0.69, 0.71 vs. 0.68, and 0.75 vs. 0.7, respectively; all age-adjusted P < 0.05). With 90 cm (male)/80 cm (female) as criteria for central obesity, WC-mid, but not WC-IC, predicted the incidence of diabetes development (age-adjusted P = 0.003). CONCLUSIONS: WC-mid is a better measurement to define central obesity than WC-IC, particularly in women.

The relationship between serum galectin-3 and serum markers of cardiac extracellular matrix turnover in heart failure patients.

BACKGROUND: A growing body of evidence links macrophage activation and fibrosis to the pathogenesis of heart failure (HF). Galectin-3 is one of the most likely mediators between macrophage activation and myocardial fibrosis. However, the exact relationship is unknown in humans. We assessed the impact of galectin-3 on serum markers of cardiac extracellular matrix (ECM) turnover in HF patients. METHODS: Patients with HF manifestations and a left ventricular ejection fraction (LVEF)

Serum vascular adhesion protein-1 is increased in acute and chronic hyperglycemia.

BACKGROUND: The relationship between serum vascular adhesion protein-1 (VAP-1) and plasma glucose in normal and drug-naïve type 2 diabetes subjects is unclear. We examined if serum VAP-1 changed acutely to oral glucose loading and analyzed the relationship between serum VAP-1, fasting plasma glucose (FPG), hemoglobin A1c, and type 2 diabetes. METHODS: Adults without history of diabetes were included. Subjects taking anti-diabetic drugs were excluded. Serum VAP-1 was analyzed by time-resolved immunofluorometric assay. RESULTS: We recruited 333 subjects (186 females and 147 males), aged 56.1 +/- 11.6 y. After glucose challenge, serum VAP-1 rose significantly at 30 min (p < 0.0001) and lasted until 2 h (p < 0.0001). The change of serum VAP-1 between fasting and 30-min postload correlated inversely to the change of plasma insulin (r = -0.21, p = 0.049). Fasting serum VAP-1 was associated with FPG in those with FPG > or = 5.55 mmol/l (p = 0.025) but not in those with FPG < 5.55 mmol/l (p = NS). Fasting serum VAP-1 were higher in diabetic subjects (p = 0.04) and correlated positively to hemoglobin A1c (r = 0.18, p = 0.002) after adjusting for age, gender, and waist circumference. CONCLUSIONS: Serum VAP-1 is increased in both acute and chronic hyperglycemia. Whether serum VAP-1 is a good biomarker for hyperglycemia-associated complications merits further investigation.