Increased Adipocyte Hypertrophy in Patients with Nascent Metabolic Syndrome.

Background and Aims: Metabolic Syndrome (MetS), a global problem, predisposes to an increased risk for type 2 diabetes and premature cardiovascular disease. While MetS is associated with central obesity, there is scanty data on adipocyte hypertrophy, increased fat cell size (FCS), in MetS. The aim of this study was to investigate FCS status in adipose tissue (AT) biopsy of patients with nascent MetS without the confounding of diabetes, cardiovascular disease, smoking, or lipid therapy. Methods and Results: Fasting blood and subcutaneous gluteal AT biopsies were obtained in MetS (n = 20) and controls (n = 19). Cardio-metabolic features, FFA levels, hsCRP, and HOMA-IR were significantly increased in patients with MetS. Waist-circumference (WC) adjusted-FCS was significantly increased in patients with MetS and increased with increasing severity of MetS. Furthermore, there were significant correlations between FCS with glucose, HDL-C, and the ratio of TG: HDL-C. There were significant correlations between FCS and FFA, as well as endotoxin and monocyte TLR4 abundance. Additionally, FCS correlated with readouts of NLRP3 Inflammasome activity. Most importantly, FCS correlated with markers of fibrosis and angiogenesis. Conclusions: In conclusion, in patients with nascent MetS, we demonstrate WC-adjusted increase in FCS from gluteal adipose tissue which correlated with cellular inflammation, fibrosis, and angiogenesis. While these preliminary observations were in gluteal fat, future studies are warranted to confirm these findings in visceral and other fat depots.

Correlates of Insulin Resistance in Nascent Metabolic Syndrome.

Background: Metabolic Syndrome (MetS), a major global problem, is a cluster of cardio-metabolic risk factors that predisposes to both type 2 diabetes mellitus (T2DM) and premature atherosclerotic cardiovascular disease (ASCVD). Insulin resistance is a major underpinning of MetS. Objectives: We investigated the relationship between insulin resistance and biomarkers of inflammation, oxidative stress, free fatty acids (FFA) levels and adipokine dysregulation in a cohort of nascent MetS. Design: This was a cross-sectional study comparing patients with MetS with matched controls. Patients and Methods: Participants included 47 patients with MetS and 41 controls. Persons with diabetes, ASCVD, smoking and macro-inflammation were excluded. Fasting blood was obtained for both plasma and monocyte isolation. Homeostasis model assessment insulin resistance index (HOMA-IR) was calculated from fasting glucose and insulin levels. Results: The patients were insulin resistant as determined by a valid measure, HOMA-IR. HOMA-IR increased with increasing severity of MetS and correlated with cardio-metabolic features, hsCRP, FFA levels, and adipose tissue insulin resistance. Insulin resistance also correlated with biomarkers of oxidative stress and both circulating and cellular biomarkers of inflammation. Receiver operating Characteristic (ROC) curve analysis revealed that HOMA-IR was an excellent predictor of MetS with an area under the curve of 0.80. Conclusion: In our patients with nascent MetS we show that they have significant insulin resistance. Based on our findings, elevated FFA levels, oxidative stress and inflammation could contribute to the insulin resistance.

The triglyceride-waist circumference index is a valid biomarker of metabolic syndrome in African Americans.

BACKGROUND: The hypertriglyceridemia waist (HTGW) phenotype is associated with visceral adiposity, metabolic syndrome, type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD). Since the cut points for abdominal obesity and hypertriglyceridemia, differ for different race groups, investigators have developed the product of triglycerides (TG) and waist circumference (WC) as the TG.WC index. We compared this TG.WC index to the TG:HDL-C ratio in the National Health and Nutrition Examination Survey (NHANES) study to predict metabolic syndrome (MetS) in African Americans (AAs). METHODS: Participants included 950 AAs and 2651 non-Hispanic Whites (NHWs) for comparison from the NHANES data set. Persons with diabetes, ASCVD and macro-inflammation were excluded. Fasting blood was obtained for lipids, insulin and CRP. RESULTS: In AAs and NHWs, both the TG.WC index and TG:HDL-C ratio were significantly increased in MetS patients. Also, both increased with increasing severity of MetS and correlated with all features of MetS, insulin resistance and inflammation. Receiver operating characteristic (ROC) curve analysis showed that discrimination with TG.WC for MetS was superior to the TG:HDL-C ratio especially in AAs. CONCLUSIONS: TG.WC index is a superior biomarker to TG:HDL-C for predicting MetS in AAs despite their lower TG levels.

Prediction of Mortality and Major Adverse Kidney Events in Critically Ill Patients With Acute Kidney Injury.

RATIONALE & OBJECTIVE: Risk prediction tools for assisting acute kidney injury (AKI) management have focused on AKI onset but have infrequently addressed kidney recovery. We developed clinical models for risk stratification of mortality and major adverse kidney events (MAKE) in critically ill patients with incident AKI. STUDY DESIGN: Multicenter cohort study. SETTING & PARTICIPANTS: 9,587 adult patients admitted to heterogeneous intensive care units (ICUs; March 2009 to February 2017) who experienced AKI within the first 3 days of their ICU stays. PREDICTORS: Multimodal clinical data consisting of 71 features collected in the first 3 days of ICU stay. OUTCOMES: (1) Hospital mortality and (2) MAKE, defined as the composite of death during hospitalization or within 120 days of discharge, receipt of kidney replacement therapy in the last 48 hours of hospital stay, initiation of maintenance kidney replacement therapy within 120 days, or a ≥50% decrease in estimated glomerular filtration rate from baseline to 120 days from hospital discharge. ANALYTICAL APPROACH: Four machine-learning algorithms (logistic regression, random forest, support vector machine, and extreme gradient boosting) and the SHAP (Shapley Additive Explanations) framework were used for feature selection and interpretation. Model performance was evaluated by 10-fold cross-validation and external validation. RESULTS: One developed model including 15 features outperformed the SOFA (Sequential Organ Failure Assessment) score for the prediction of hospital mortality, with areas under the curve of 0.79 (95% CI, 0.79-0.80) and 0.71 (95% CI, 0.71-0.71) in the development cohort and 0.74 (95% CI, 0.73-0.74) and 0.71 (95% CI, 0.71-0.71) in the validation cohort (P < 0.001 for both). A second developed model including 14 features outperformed KDIGO (Kidney Disease: Improving Global Outcomes) AKI severity staging for the prediction of MAKE: 0.78 (95% CI, 0.78-0.78) versus 0.66 (95% CI, 0.66-0.66) in the development cohort and 0.73 (95% CI, 0.72-0.74) versus 0.67 (95% CI, 0.67-0.67) in the validation cohort (P < 0.001 for both). LIMITATIONS: The models are applicable only to critically ill adult patients with incident AKI within the first 3 days of an ICU stay. CONCLUSIONS: The reported clinical models exhibited better performance for mortality and kidney recovery prediction than standard scoring tools commonly used in critically ill patients with AKI in the ICU. Additional validation is needed to support the utility and implementation of these models. PLAIN-LANGUAGE SUMMARY: Acute kidney injury (AKI) occurs commonly in critically ill patients admitted to the intensive care unit (ICU) and is associated with high morbidity and mortality rates. Prediction of mortality and recovery after an episode of AKI may assist bedside decision making. In this report, we describe the development and validation of a clinical model using data from the first 3 days of an ICU stay to predict hospital mortality and major adverse kidney events occurring as long as 120 days after hospital discharge among critically ill adult patients who experienced AKI within the first 3 days of an ICU stay. The proposed clinical models exhibited good performance for outcome prediction and, if further validated, could enable risk stratification for timely interventions that promote kidney recovery.

A comparison of the ratios of C-reactive protein and triglycerides to high-density lipoprotein-cholesterol as biomarkers of metabolic syndrome in African Americans and non-Hispanic Whites.

AIMS: The ratio of triglycerides (TG) to high density lipoprotein-cholesterol (HDL-C) is a validated biomarker of insulin resistance and metabolic syndrome (MetS). In African-Americans (AA) there is concern about this ratio because their mean TG level is lower than the general population. As an alternative approach, we examined the CRP:HDL-C ratio in both AA and non-Hispanic whites (NHW) in the NHANES study for its association with MetS. METHODS: A total of n = 3541 individuals were studied from the NHANES data. Fasting blood samples were obtained for lipids, insulin, and CRP. TG and CRP ratios to HDL-C were calculated. RESULTS: The TG:HDL-C ratio was significantly increased in NHW compared to AA, but the CRP:HDL-C ratio did not differ between NHW and AA groups. Both ratios were significantly increased in MetS patients versus controls (both races) and increased with greater severity of MetS. Receiver Operating Characteristic (ROC) curve analysis showed that the TG:HDL-C area under the curve was superior to CRP:HDL-C in predicting MetS in both AA and NHW patients. CONCLUSION: In this large NHANES study, the TG:HDL-C ratio is a superior predictor of MetS in both AA and NHW persons despite the lower TG levels in AA persons.

Effect of a late afternoon/early evening bout of aerobic exercise on postprandial lipid and lipoprotein particle responses to a high-sugar meal breakfast the following day in postmenopausal women: a randomized cross-over study.

High-sugar consumption is related to dyslipidemia. How acute exercise affects postprandial lipid and lipoprotein particle responses to a high-sugar meal (HSM) in postmenopausal women is unclear. We examined the effects of a late afternoon/early evening bout of aerobic exercise on postprandial lipid and lipoprotein particle responses to a HSM breakfast the following day in 22 postmenopausal women. Subjects underwent exercise (EX) and no exercise (NE) conditions in the evening 13-16 h before the HSM breakfast consumption, in a random order. During the EX condition, subjects performed supervised aerobic exercise for 60 min at 75% of age-predicted maximum heart rate. The HSM (75.6% carbohydrate and 33% energy needs) was consumed after a 12-h fast. Serum lipids and lipoproteins were assessed at baseline and postprandially (60, 120, 180 min). Repeated measures analysis showed significantly lower area under the curve (geometric means [95% CI]) for triglycerides (TG) (2.96[2.43, 3.61] vs. 3.24[2.70, 3.88] mmol/L*hr; p = 0.049) and very low density lipoprotein particles (VLDLP) (114.6[88.2, 148.9] vs. 134.3[108.1, 166.9] nmol/L*hr; p = 0.02) during the EX versus NE condition. There were no condition effects for other variables. In conclusion, the EX versus NE condition lowered postprandial AUC for TG and VLDLP following HSM consumption in postmenopausal women.Trial Registration: ClinicalTrials.gov Identifier: NCT02919488.

Comparison of the triglyceride-waist circumference and the C-reactive protein-waist circumference indices in nascent metabolic syndrome.

The Hypertriglyceridemia waist (HTGW) appears to be a valid measure of visceral adiposity, metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD). Since the cut points differ for different race groups recent studies have instead used the simplified product of triglycerides and waist circumference (TG.WC). In our patients with nascent MetS (without the confounding of T2DM, ASCVD, smoking and macro-inflammation) we found that only 41% had an increased HTGW. Since MetS is a pro-inflammatory disorder we compared the product of CRP to WC (CRP.WC) to TG.WC in our patients with nascent MetS as biomarkers. Patients with MetS (n=58) and matched controls (n=44) were recruited. Fasting blood samples were obtained for routine laboratories including the lipid profile, insulin, and adipokines. Both the TG.WC and CRP.WC indices were significantly increased in MetS and both increased with increasing severity of MetS. Whilst both correlated with cardio-metabolic features and insulin resistance, only the CRP.WC correlated significantly with adiponectin, an adipokine largely deriving from visceral adipose tissue. The TG.WC correlated with LDL-cholesterol which was not increased in this group. Receiver Operating Characteristic (ROC) curve analysis showed that both ratios showed good discrimination for MetS with no significant differences between ratios. Thus both the TG.WC and CRP.WC indices are significantly increased in patients with nascent MetS and appear to be valid biomarkers of MetS.

Differential effects of eplerenone versus amlodipine on muscle metaboreflex function in hypertensive humans.

Numerous studies have demonstrated that sympathetic nervous system overactivation during exercise in hypertensive rodents and humans is due, in part, to an exaggerated reflex response known as the exercise pressor reflex. Our prior studies have implicated a key role of mineralocorticoid receptor activation in mediating an augmented exercise pressor reflex in spontaneously hypertensive rats, which is mitigated by blockade with eplerenone. However, the effect of eplerenone on exercise pressor reflex has not been assessed in human hypertension. Accordingly, the authors performed a randomized crossover study to compare the effects of eplerenone to another antihypertensive drug from a different class amlodipine on sympathetic nerve activity (SNA) in 14 patients with uncomplicated hypertension. The authors found that amlodipine unexpectedly augmented the increase in SNA during the second minute of isometric handgrip, which persisted into the post-exercise circulatory arrest period (∆ SNA, from rest of 15 ± 2 vs. 9 ± 2 vs. 10 ± 2 bursts/min, amlodipine vs. baseline vs. eplerenone, respectively, p < .01), suggesting an exaggerated muscle metaboreflex function. Eplerenone did not alter sympathetic responses to exercise or post-exercise circulatory arrest in the same hypertensive individuals. In conclusions, our studies provide the first direct evidence for a potentially unfavorable potentiation of muscle metaboreflex by amlodipine during isometric handgrip exercise in hypertensive patients whereas eplerenone has no significant effect. Our study may have clinical implications in terms of selection of antihypertensive agents that have the least detrimental effects on sympathetic neural responses to isometric exercise.

Hypophosphatemia in acute liver failure of a broad range of etiologies is associated with phosphaturia without kidney damage or phosphatonin elevation.

Hypophosphatemia is a common and dangerous complication of acute liver failure (ALF) of various etiologies. While various mechanisms for ALF-associated hypophosphatemia have been proposed including high phosphate uptake into regenerating hepatocytes, acetaminophen (APAP)-associated hypophosphatemia was linked to renal phosphate wasting, and APAP-induced renal tubular injury was proposed as underlying mechanism. We studied 30 normophosphatemic and 46 hypophosphatemic (serum phosphate < 2.5 mg/dL) patients from the Acute Liver Failure Study Group registry with APAP- or non-APAP-induced ALF. Since kidney injury affects phosphate excretion, patients with elevated serum creatinine (>1.2 mg/dL) were excluded. Maximal amount of renal tubular phosphate reabsorption per filtered volume (TmP/GFR) was calculated from simultaneous serum and urine phosphate and creatinine levels to assess renal phosphate handling. Instead of enhanced renal phosphate reabsorption as would be expected during hypophosphatemia of non-renal causes, serum phosphate was positively correlated with TmP/GFR in both APAP- and non-APAP-induced ALF patients (R2 = 0.66 and 0.46, respectively; both P < 0.0001), indicating renal phosphate wasting. Surprisingly, there was no evidence of kidney damage based on urinary markers including neutrophil gelatinase-associated lipocalin and cystatin C even in the APAP group. Additionally, there was no evidence that the known serum phosphatonins parathyroid hormone, fibroblast growth factor 23, and α-Klotho contribute to the observed hypophosphatemia. We conclude that the observed hypophosphatemia with renal phosphate wasting in both APAP- and non-APAP-mediated ALF is likely the result of renal tubular phosphate leak from yet-to-be identified factor(s) with no evidence for proximal tubular damage or contribution of known phosphatonins.

The Ratios of Triglycerides and C-reactive protein to High density-lipoprotein -cholesterol as valid biochemical markers of the Nascent Metabolic Syndrome.

Aims: Metabolic syndrome (MetS), a cardiometabolic cluster, is a major global problem. The ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) is a good biomarker of MetS in certain populations  C-reactive protein (CRP) has also been also shown to be a biomarker of MetS. Since CRP captures inflammation, we compared the ratios of TG to HDL-C and CRP to HDL-C in patients with nascent MetS.Methods: Patients with MetS (n = 58) and matched controls (n = 44) were recruited. Fasting blood samples were obtained for routine laboratories, insulin, and adipokines. TG and CRP ratios to HDL-C were calculated. Data were analyzed statistically.Results: Both the TG to HDL-C and CRP to HDL-C ratios were significantly increased in MetS and both increased with increasing severity of MetS. Whilst both correlated with cardiometabolic features and insulin resistance, only the CRP to HDL-C ratio correlated significantly with adiponectin and leptin. Receiver operating characteristic curve analysis showed that both ratios showed excellent discrimination for MetS with no significant differences between ratios.Conclusions: Thus both the TG to HDL-C and CRP to HDL-C ratios are significantly increased in patients with nascent MetS and appear to be valid biomarkers of MetS. However, these preliminary findings with CRP: HDL-C need confirmation in large prospective studies and could have important implications for assessing cardiometabolic risk in African Americans, an under-served population.

Impact of age and renal function on urine chemistry in patients with calcium oxalate kidney stones.

Nephrolithiasis is associated with an increased risk of chronic kidney disease, and its incidence varies with age. However, little is known on the combined impact of aging and declining renal function on urinary risk factors for calcium oxalate stone formation. A retrospective analysis was performed on 24-h urine collections from 993 calcium oxalate stone-forming patients. We first tested for interactions between age and creatinine clearance on various urinary determinants of calcium oxalate nephrolithiasis, and then examined their separate and combined effects in univariable and multivariable analyses adjusting for demographic and biochemical covariates. We identified significant interactions between age and creatinine clearance in predicting 24-h urine pH, calcium, and citrate. In view of the small number of stone formers with low creatinine clearance, we limited further regression analyses to patients with creatinine clearance ≥ 60 mL/min. In multivariable analyses, urine citrate, oxalate, and total volume were positively correlated with age, whereas urine pH, citrate, calcium, oxalate, total volume, and RSR of calcium oxalate all significantly decreased with lower creatinine clearance. A decrease in creatinine clearance from 120 to 60 mL/min was associated with clinically significant decreases in the daily excretion rate of citrate (by 188 mg/day), calcium (by 33 mg/day), and oxalate (by 4 mg/day), and in RSR calcium oxalate (by 1.84). Age and creatinine clearance are significant and independent predictors of several urinary determinants of calcium oxalate nephrolithiasis. The impacts of aging and declining renal function should be considered during the management of calcium oxalate stone-forming patients.

Metabolites that activate the inflammasome in nascent metabolic syndrome.

BACKGROUND: Metabolic Syndrome (MetS) is a cardio-metabolic cluster that increases the risk of type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD). Whilst it affects 35% of the American adult population, its pathogenesis remains to be elucidated. Both insulin resistance and increased inflammation appear to be pivotal mechanisms. The NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome, an intracellular multi-protein complex, is crucial in the activation of Caspase 1, resulting in an increase in both IL-1and IL-18. In this preliminary report we examined the relationship between metabolites from our exploratory metabolomics studies with the NLRP3 inflammasome activity in the adipose tissue of patients with nascent MetS. PATIENT AND METHODS: This study comprised patients with nascent MetS matched with controls. All patients in this study had normal renal and hepatic function. Metabolites were analyzed from frozen early morning urine samples and correlated with adipose tissue Caspase 1, interleukin-1, and interleukin-18 density. RESULTS: Caspase 1, a marker of NLRP3 inflammasome activity, was significantly elevated in patients with nascent MetS compared to controls. Isoleucine, GABA, Carnitine and PC34: 2 were also significantly increased in patients with MetS. Caspase1 correlated positively with Isoleucine, GABA, Carnitine, and PC34:2. CONCLUSION: We make the novel observation that the NLRP3 inflammasome activity is correlated with certain metabolites (Isoleucine, GABA, Carnitine and PC34:2) and hypothesize that they could trigger increased NLRP3 Inflammasome activity in MetS. However, these preliminary ,hypothesis generating novel findings need confirmation in larger studies of the metabolome and inflammasome.

The risk of depression among racially diverse people living with HIV: the impact of HIV viral suppression.

Understanding the correlates of depression in HIV patients can help identify groups whose members are at increased risk for depression. We conducted a cross-sectional retrospective study among racially diverse, indigent patients living with HIV (PLWH) who were obtaining care in an urban safety-net hospital system and had completed a Patient Health Questionnaire-9 (PHQ-9) in 2014 or 2015. We collected demographics, HIV risk factors, HIV viral loads, CD4 counts, missed visits, and emergency department (ED) visits. Data from the Substance Abuse and Mental Illness Symptoms Screener (SAMISS) were abstracted. Missing data on substance use and CD4 cell counts were imputed to examine the odds of depression (PHQ-9 ≥ 10) by multivariable analysis for a complete case and sensitivity analysis. Stratified analysis by HIV viral suppression (VS) was used to determine the odds of depression among subgroups. Of the 5126 HIV patients (70.8% male,56.3% Black, 44.6% MSM, 6.0% IDU), 1271 (24.8%) experienced depression (PHQ ≥ 10). In a multivariable logistic model female gender, White race, injection drug use (IDU) or men who have sex with men (MSM) as an HIV risk factor, making ≥1 ED visit, having missed any HIV visit, having AIDS, and having a positive drug screen by SAMISS increased the odds for depression. Those who had achieved HIV VS or received efavirenz had lower odds of depression. Even among those with AIDS, those failing to achieve VS were at increased odds for depression, whereas those achieving VS were not. Moderate to severe depression is prevalent among PLWH. Among those with AIDS, HIV VS modifies the odds of depression.

Increased inflammasome activity in subcutaneous adipose tissue of patients with metabolic syndrome.

AIMS: The metabolic syndrome (MetS) is an inflammatory disorder associated with an increased risk for diabetes and atherosclerotic cardiovascular disease (ASCVD). Studies in patients and animal models of obesity and diabetes have shown increased NOD-like receptor family pyrin domain containing 3 (NLPR3) inflammasome activity. However, there is scanty data on the activity of the NLRP3 inflammasome in patients with nascent MetS. The aim of this study was to determine the status of the inflammasome in subcutaneous adipose tissue (SAT) of patients with nascent MetS without concomitant diabetes, ASCVD and smoking. MATERIALS AND METHODS: Patients with nascent MetS and controls were recruited from Sacramento County. Fasting blood samples were collected for biomediators of inflammation and SAT was obtained by biopsy for immunohistochemical (IHC) staining for caspase 1, IL-1ß and IL-18. RESULTS: Caspase1, a marker of inflammasome activity and its downstream mediators IL-1ß and IL-18 were significantly increased in SAT of patients with MetS compared to controls. Significant positive correlations of caspase 1 were obtained with certain cardio-metabolic features, biomediators of inflammation and markers of angiogenesis and fibrosis in SAT. Both mast cell and eosinophil abundance but not macrophage density correlated with caspase1. CONCLUSIONS: We make the novel observation that the SAT of patients with nascent MetS displays increased NLRP3 inflammasome activity manifest by increased caspase 1 in SAT and this may contribute to increased insulin resistance, inflammation and SAT fibrosis in these patients.

Spot urinary citrate-to-creatinine ratio is a marker for acid-base status in chronic kidney disease.

Due to multiple compensating mechanisms, the serum bicarbonate concentration is a relatively insensitive marker of acid-base status; especially in chronic kidney disease (CKD). This is a major drawback that impairs the ability to diagnose acid excess or monitor alkali therapy. We postulated that it is more logical to measure the compensatory defense mechanism(s) rather than the defended parameter, which remains normal if the compensation is successful. Therefore, a retrospective cross-sectional study was performed in 1733 stone formers along with a prospective cross-sectional study of 22 individuals with normal kidney function and 50 patients in different stages of CKD. While serum bicarbonate was flat and did not fall below the reference range until near CKD stage 5, citrate excretion (24-hour urinary citrate excretion rate; urinary citrate-to-creatinine ratio, in the retrospective analysis, and spot urinary citrate-to-creatinine ratio in the prospective study) progressively and significantly declined starting from CKD stage 2. Following an acute acid load in 25 participants with a wide range of estimated glomerular filtration rates, the urinary citrate-to-creatinine ratio inversely and significantly associated with acid accumulation, whereas serum bicarbonate did not. We compared changes in serum bicarbonate and urinary citrate-to-creatinine ratio in response to alkali therapy in patients with CKD stage 3 or 4 started on potassium citrate in our kidney stone database. With alkali therapy, there was no change in serum bicarbonate, but the urinary citrate-to-creatinine ratio rose consistently in all patients adherent to potassium citrate therapy. Thus, the urinary citrate-to-creatinine ratio (the defense mechanism) is a potential easily implementable, pragmatic, and a superior parameter to serum bicarbonate (the defended entity) to assess acid-base status, and monitor alkali therapy. Additional studies are needed before a clinical test can be devised.

The platelet to high density lipoprotein -cholesterol ratio is a valid biomarker of nascent metabolic syndrome.

AIMS: The metabolic syndrome (MetS) is a major global problem, and inflammation and insulin resistance appear to be key underpinnings in this cardio-metabolic cluster. MetS predisposes to an increased risk of diabetes and atherosclerotic cardiovascular disease (ASCVD). It has a procoagulant diathesis which included increased platelet activity and impaired fibrinolysis. High density lipoprotein (HDL) appears to be anti-thrombotic. Accordingly, we examined the ratios between platelets to HDL-cholesterol(C) and adiponectin (Adipo) in patients with nascent MetS without the confounding of diabetes, ASCVD and smoking to determine their validity as biomarkers of MetS. METHODS: Patients with nascent MetS (n = 58) and matched controls (n = 44) were recruited. Fasting blood samples were obtained for complete blood counts, basic metabolic panel, lipids, insulin, and Adipo. Ratios of platelets to HDL-C and Adipo were calculated. RESULTS: Following adjustment for adiposity, only the platelet: HDL ratio was significantly increased in MetS and increased with severity of MetS. Receiver operating characteristic curve analysis showed that the platelet: HDL-C area under the curve (AUC) significantly added to both platelets and platelet lymphocyte ratio AUCs. Also the platelet: HDL-C ratio correlated with all cardio-metabolic features of MetS, high sensitivity C-reactive protein, insulin resistance chemerin, and leptin. CONCLUSIONS: The ratio of platelets: HDL-C is significantly increased in patients with nascent MetS and appear to be a valid biomarker of MetS. It could also emerge as a biomarker for athero-thrombotic risk. However, these preliminary findings need confirmation in large prospective studies.

The use of automated data extraction tools to develop a solid organ transplant registry: Proof of concept study of bloodstream infections.

BACKGROUND: We created an electronic health record-based registry using automated data extraction tools to study the epidemiology of bloodstream infections (BSI) in solid organ transplant recipients. The overarching goal was to determine the usefulness of an electronic health record-based registry using data extraction tools for clinical research in solid organ transplantation. METHODS: We performed a retrospective single-center cohort study of adult solid organ transplant recipients from 2010 to 2015. Extraction tools were used to retrieve data from the electronic health record, which was integrated with national data sources. Electronic health records of subjects with positive blood cultures were manually adjudicated using consensus definitions. One-year cumulative incidence, risk factors for BSI acquisition, and 1-year mortality were analyzed by Kaplan-Meier method and Cox modeling, and 30-day mortality with logistic regression. RESULTS: In 917 solid organ transplant recipients the cumulative incidence of BSI was 8.4% (95% confidence interval 6.8-10.4) with central line-associated BSI as the most common source. The proportion of multidrug-resistant isolates increased from 0% in 2010 to 47% in 2015 (p = 0.03). BSI was the strongest risk factor for 1-year mortality (HR=8.44; 4.99-14.27; p<0.001). In 11 of 14 deaths, BSI was the main cause or contributory in patients with non-rapidly fatal underlying conditions. CONCLUSIONS: Our study illustrates the usefulness of an electronic health record-based registry using automated extraction tools for clinical research in the field of solid organ transplantation. A BSI reduces the 1-year survival of solid organ transplant recipients. The most common sources of BSIs in our studies are preventable.