Calcio sérico total y calcio corregido como predictores de severidad en pancreatitis aguda

ObjectivesTo evaluate total serum calcium (TC) and albumin-corrected calcium (ACC) as prognostic severity factors in acute pancreatitis (AP).MethodsNinety-six patients were included in the study. They were diagnosed with AP and admitted to the Hospital Regional de Veracruz within the time frame of January 2010 to December 2012. AP severity was determined through the updated Atlanta Classification (2013). TC and ACC values were measured in the first 24 hours of admittance and the percentages of sensitivity (S), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR + ), and negative likelihood ratio (LR-) were calculated through ROC curves and contingency tables.ResultsIn accordance with the updated Atlanta Classification, 70 patients presented with mild AP, 17 with moderately severe AP, and 9 with severe AP. Of the patient total, 61.5% were women, and 69.8% presented with biliary etiology. The maximum TC cut-off point was 7.5 mg/dL, with values of S, 67%; Sp, 82%; PPV, 27%, and NPV, 96%. The maximum ACC cut-off point was 7.5 mg/dL, with values of S, 67%; Sp, 90%; PPV, 40%; NPV, 96%. Both had values similar to those of the Ranson and APACHE II prognostic scales.ConclusionsTC and ACC, measured within the first 24 hours, are useful severity predictors in acute pancreatitis, with sensitivity and predictive values comparable or superior to those of the conventional prognostic scales.     

Perfil clínico de los pacientes tratados con evolocumab en unidades hospitalarias de nefrología en España (RETOSS-NEFRO)

Background and objectiveTo describe the clinical characteristics, the reasons for initiating therapy and the effects of treatment in the initial phase of evolocumab availability in the Nephrology Units of Spain.Material and methodsRetrospective, observational and multicentric study that included patients initiating treatment with evolocumab (from February 2016 to August 2018), in 15 Nephrology Units in Spain. The demographic and clinical characteristics of the patients, the lipid lowering treatment and the evolution of the lipid profiles between 24 weeks pre-initiation and 12 ± 4 weeks post-initiation of evolocumab were reviewed.ResultsSixty patients were enrolled: 53.3% women; mean (SD) age, 56.9 (12.8) years, 45.0% with familial hypercholesterolemia (FH) (5.0% homozygous and 40.0% heterozygous) and 65.0% with atherosclerotic cardiovascular (CV) disease. The mean (SD) eGFR was 62.6 (30.0) ml/min/1.73 m² (51.7% of patients had eGFR < 60 ml/min/1.73 m² [CKD stage > 2]), 50.0% had proteinuria (>300 mg/g) and 10.0% had nephrotic syndrome. Other CV risk factors were hypertension (75.0%), diabetes (25.0%), and smoking (21.7%). A 40.0% of patients were statin intolerant. At evolocumab initiation, 41.7% of patients were on a high-intensity statin, 18.3% on moderate intensity statin and 50.0% were receiving ezetimibe. Mean (SD) LDL-c at evolocumab initiation was 179.7 (62.9) mg/dL (53.4% of patients with LDL-c≥160 mg/dL and 29.3%≥190 mg/dL). After 12 weeks, evolocumab resulted in LDL-c reductions of 60.1%. At week 12, 90.0% of patients reached LDL-c levels <100 mg/dL, 70.0% <70 mg/dL, and 55.0% <55 mg/dL, while mean eGFR levels and statin use were remained stable.ConclusionIn Nephrology Units of Spain, evolocumab was predominantly prescribed in patients with FH, chronic renal disease (CRD>2) and secondary prevention, with LDL-c levels above those recommended by the guidelines. Evolocumab used in clinical practice significantly reduced the LDL-c levels in all patients included in the study.     

Routine laboratory tests to risk-stratify patients with chronic coronary artery disease

BackgroundSeveral biohumoral variables, taken individually, are predictors of prognosis in patients with chronic coronary artery disease (CAD). We hypothesized that taken together, laboratory tests provide prognostic information that is additive to a complete diagnostic work-up.MethodsWe prospectively examined 2370 consecutive patients with chronic CAD, as shown by a >50% coronary stenosis (in 95% of patients), previous coronary revascularization (in 31% of patients), and/or previous myocardial infarction (MI, in 54% of patients). We tested the ability of laboratory and clinical variables to predict future cardiac events (cardiac death and non-fatal MI).ResultsDuring follow-up (median, 46 months), 147 patients (6.2%) died from cardiac causes and 81 (3.4%) experienced a non-fatal MI. Using multivariate analysis, after adjustment for clinical variables (including left ventricular ejection fraction and angiographic extent of coronary stenoses), a high-density lipoprotein cholesterol (HDLc) concentration < 35 mg/dL (p < 0.0001), a neutrophil-to-lymphocyte ratio >2.4 (p = 0.0014), and an fT3 serum level < 2.1 pg/mL with normal thyrotropin (low-T3 syndrome) (p = 0.0260) showed an independent and incremental prognostic value, and were associated with an increase in the rate of cardiac events of 86%, 57% and 41%, respectively. When these variables were added to clinical and instrumental variables, the prognostic power of the model increased significantly (global chi-square improvement: from 157.01 to 185.07, p < 0.0001).ConclusionLow HDLc, high neutrophil-to-lymphocyte ratio and low-T3 syndrome, both individually and taken together, provide prognostic information that is independent of and incremental to the main clinical and instrumental findings.     

Development of a risk indicator score for the identification of interstitial lung disease in patients with rheumatoid arthritis

BackgroundClinically evident interstitial lung disease (ILD) affects 10%–42% of RA patients with prognostic implications. The aim of this study was to discern which factors are associated with the presence of ILD in RA patients and to develop a score that could help to stratify the risk of having ILD in RA patients.MethodsCase–control study. We included RA patients recruited from ILD and rheumatology clinics. We retrieved the following data: gender, age, presence of extra articular manifestations, disease activity scores, antibodies status, ESR, and medication use. Multivariate logistic regression was performed. A risk indicator score was developed.ResultsOf 118 patients included in this study, 52 (44%) had RA-ILD (cases) and 66 (56%) had RA without ILD (controls). Twenty-six patients were male (22%), the mean age was 56.6 ± 15.6 years. Five variables were significantly associated with the presence of ILD: male gender, smoking, extraarticular manifestations, a CDAI score > 28, and ESR > 80 mm/h. The AUC of the final model curve was 0.86 (95%CI 0.79–0.92). Two potential cut-off points of the risk indicator score were chosen: a value of 2 points showed a sensitivity of 90.38% and a specificity of 63.64%, while a value of 4 points showed a sensitivity of 51.9% and a specificity of 90.9%.ConclusionThis study identified risk factors that could help identify which RA patients are at risk of having ILD through the development of a risk indicator score. This score needs to be validated in an independent cohort.     

Screening for impaired fasting glucose and diabetes using available health plan data

AimsTo develop and validate prediction equations to identify individuals at high risk for type 2 diabetes using existing health plan data.MethodsHealth plan data from 2005 to 2009 from 18,527 members of a Midwestern HMO without diabetes, 6% of whom had fasting plasma glucose (FPG) ≥ 110 mg/dL, and health plan data from 2005 to 2006 from 368,025 members of a West Coast-integrated delivery system without diabetes, 13% of whom had FPG ≥ 110 mg/dL were analyzed. Within each health plan, we used multiple logistic regression to develop equations to predict FPG ≥ 110 mg/dL for half of the population and validated the equations using the other half. We then externally validated the equations in the other health plan.ResultsAreas under the curve for the most parsimonious equations were 0.665 to 0.729 when validated internally. Positive predictive values were 14% to 32% when validated internally and 14% to 29% when validated externally.ConclusionMultivariate logistic regression equations can be applied to existing health plan data to efficiently identify persons at higher risk for dysglycemia who might benefit from definitive diagnostic testing and interventions to prevent or treat diabetes.     

Influencia del tratamiento biológico en los factores de riesgo cardiovascular de los pacientes con enfermedad inflamatoria intestinal

IntroductionChronic immune-mediated diseases, including inflammatory bowel disease (IBD), present an increased risk of developing early atherosclerosis and cardiovascular events (CVE) at early age.ObjectiveTo describe the baseline and 1-year cardiovascular profile of patients with IBD according to the biologic treatment received, taking into account the inflammatory activity.Patients and methodsIt is a retrospective, observational study that included 374 patients. Cardiovascular risk factors (CVRF) and CVE were collected at the baseline visit and at one-year follow-up to describe the cardiovascular risk according to the biological treatment received, also assessing clinical and biological remission.ResultsA total of 374 patients were included: 146 (38.73%) were treated with Infliximab, 128 (33.95%) with adalimumab, 61 (16.18%) with ustekinumab and 42 (11.14%) with vedolizumab.The changes in blood glucose levels are [86.31 mg/dL (84.57–88.06) vs. 89.25 mg/dL (87.54–90.96), P=.001] for those treated with antiTNFα and [86.52 mg/dL (83.48–89.55) vs. 89.44 mg/dL (85.77–93.11), P=.11] in the other group.In the group treated with antiTNFα total cholesterol values at baseline visit are [169.40 mg/dL (164.97–173.83) vs. 177.40 mg/dL (172.75–182.05) at one year of treatment, P=<.001], those of HDL [50.22 mg/dL (48.39–52.04) vs. 54.26 mg/dL (52.46–56.07), P=<.001] and those of triglycerides [114.77 mg/dL (106.36–123.18) vs. 121.83 mg/dL (112.11–131.54), P=.054].Regarding weight, an increase was observed, both in those patients treated with antiTNFα [71.39 kg (69.53–73.25) vs. 72.87 kg (71.05–74.70), P<.001], and in the group treated with ustekinumab and vedolizumab [67.59 kg (64.10–71.08) vs. 69.43 kg (65.65–73.04), P=.003].Concerning CVE, no significant differences were observed neither according to the drug used (p = 0.36), nor according to personal history of CVE (P=.23) nor according to inflammatory activity (P=.46).ConclusionsOur results on a real cohort of patients with IBD treated with biologic drugs show a better control of certain cardiovascular parameters such as CRP or HDL, but a worsening of others such as total cholesterol or triglycerides, regardless of the treatment. Therefore, it is possibly the disease control and not the therapeutic target used, the one that affect the cardiovascular risk of these patients.     

Etelcalcetide controls secondary hyperparathyroidism and raises sclerostin levels in hemodialysis patients previously uncontrolled with cinacalcet

IntroductionThere is scarce clinical experience with etelcalcetide in patients with secondary hyperparathyroidism uncontrolled with cinacalcet. The effect of etelcalcetide on serum sclerostin levels remains to be clarified.Materials and methodsProspective cohort study in prevalent hemodialysis patients with uncontrolled sHPT under cinacalcet for at least 3 months, mean parathyroid hormone (PTH) > 800 pg/mL and calcium (Ca) > 8.3 mg/dL. Etelcalcetide 5 mg IV/HD was initiated after cinacalcet washout. Levels of PTH, Ca, and phosphorus (Pi) followed monthly for 6 months. Plasma sclerostin levels measured before etelcalcetide treatment and after 6 months.ResultsThirty-four patients were enrolled, 19 (55.9%) male gender. Mean age 60.7 (± 12.3) years; median time on HD 82.5 (7–296) months and median cinacalcet dose was 180 mg/week (Interquartile Range: 180–270).Serum Ca, Pi and PTH levels showed a significant reduction after etelcalcetide treatment from 8.8 mg/dL, 5.4 mg/dL and 1005 pg/mL to 8.1 mg/dL (p = 0.08), 4.9 mg/dL (p = 0.01) and 702 pg/mL (p < 0.001), respectively. Median etelcalcetide dose remained at 5 mg/HD. Plasma sclerostin concentration increased from 35.66 pmol/L (IQR11.94–54.58) to 71.05 pmol/L (IQR54.43–84.91) (p < 0.0001).ConclusionEtelcalcetide improved sHPT control in this group of patients, previously under cinacalcet treatment, and significantly increased plasma sclerostin concentration. The impact of etelcalcetide treatment on sclerostin levels is a novel finding.     

Plasmapheresis as treatment for hyperlipidemic pancreatitis

BackgroundSevere hypertriglyceridemia with an accumulation of chylomicrons and triglyceride figures > 1000 mg/dL can cause acute pancreatitis, a potentially fatal complication. The option of rapid reduction in triglyceride concentrations is attractive and possible with plasmapheresis.MethodsWe present the results of an analysis of 11 patients admitted to the intensive care unit with severe hypertriglyceridemic pancreatitis and treated with plasmapheresis. The procedure was repeated until serum triglycerides were below 1000 mg/dL. We recorded anthropometric, clinical data as well as final outcome.ResultsIn eight patients a single plasma exchange was sufficient to reduce triglyceride figures < 1000 mg/dL. Only three patients died, all with the worst severity indexes and who experienced the longest delay before the procedure.ConclusionsOur results, together with a review of the literature, confirm the need for a randomized clinical trial to compare conventional treatment vs. plasmapheresis in patients with severe hypertriglyceridemic pancreatitis.     

Prognostic Significance of Serum Uric Acid in Patients Admitted to the Department of Medicine

BackgroundHyperuricemia has been linked to proatherogenic processes, including increased oxidative stress and leukocyte activation, and was shown to predict adverse prognosis in heart failure, renal failure, and hypertension. Recently, serum uric acid (SUA) was shown to be an independent predictor of long-term mortality in patients with cardiovascular diseases. However, the prognostic significance of SUA for the short-term outcome of admitted medical patients is unknown.MethodsInitial SUA, together with epidemiological, clinical, and laboratory data, was analyzed for a prospective cohort of 650 consecutive adult patients admitted to the department of internal medicine during a 3-month period.ResultsThe mean, median, and range of SUA at admission were 6.1 ± 2.7, 5.6, and 1.2 to 24 mg/dL, respectively. Increased SUA was significantly correlated with age, gender, comorbidities (coronary heart disease, heart failure, hypertension, diabetes, renal failure, and gout), use of diuretics, and current admission for cardiovascular diseases but not with current diagnosis of infection, malignancy, or inflammatory diseases, nor with C-reactive protein. However, SUA significantly correlated with mortality (7.7 versus 6 mg/L, P < 0.025) and was an independent predictor of mortality in a multivariate regression analysis (odds ratio: 1.11; confidence interval: 1.003-1.218; P = 0.04), with a significant difference in mortality between normal SUA (< 6 mg/dL) with 5% mortality and high SUA (> 12 mg/dL) with 27% mortality.ConclusionsInitial SUA is an independent predictor of mortality in admitted medical patients. Whether significant asymptomatic hyperuricemia should be treated remains to be determined in further studies.     

Heterogeneity of the prognostic significance of B-type natriuretic peptide levels on admission in patients hospitalized for acute heart failure syndromes

BackgroundWe hypothesized that variation in baseline characteristics of patients with acute heart failure syndromes (AHFS) affects the prognostic significance of B-type natriuretic peptide (BNP) levels because of heterogeneity of this patient population. We evaluated the association of elevated BNP levels on admission with an increased risk of adverse clinical outcomes in subgroups of patients hospitalized for AHFS.MethodsThis study included patients from the acute decompensated heart failure syndromes (ATTEND) study, a multicenter prospective cohort of 4501 AHFS patients with BNP data on admission.ResultsThe geometric mean BNP level was 654.9 pg/mL (95% confidence interval: 636.1–674.2), and the optimal cut-off value for all-cause death was 1157 pg/mL. All-cause mortality after admission was significantly higher in patients with high BNP levels (> 1157 pg/mL) than in those with low BNP levels (≤ 1157 pg/mL) (median follow-up: 508 days, log-rank P < 0.001). Subgroup analyses were performed to evaluate the heterogeneity of the prognostic significance of BNP levels. The effect of high BNP levels on the risk of all-cause mortality was significantly greater in the subgroup of patients with a non-hypertensive etiology, low creatinine levels (< 1.3 mg/dL), and high sodium levels (≥ 135 mEq/L) than in those without these factors (P = 0.024, P < 0.001, and P < 0.001 for the interaction, respectively).ConclusionsThe present analysis shows that underlying etiology of heart failure (i.e., hypertensive), renal function, and sodium levels should be considered for assessing the clinical significance of elevated BNP levels on admission in relation to the risk of adverse outcome after hospitalization for AHFS.     

Glycaemic control for painful diabetic peripheral neuropathy is more than fasting plasma glucose and glycated haemoglobin

BackgroundThe relationship between postprandial hyperglycaemia and diabetic peripheral neuropathy (DPN), whether painful or painless, has yet to be determined. Thus, the aim of this study was to investigate the relationship in patients with type 2 diabetes (T2D).MethodsThis cross-sectional study was conducted in adults with T2D between January and October 2013. Blood samples were collected after overnight fasting every 3 months prior to enrolment. For this study, increased postprandial glycaemic exposure was defined as high glycated haemoglobin (HbA_1c) and near-normal mean fasting plasma glucose (FPG) levels. Both painless and painful DPN were evaluated using two validated tools, the Michigan Neuropathy Screening Instrument (MNSI) and Douleur Neuropathique 4 (DN4) questionnaire.ResultsThis study included 1040 participants with mean FPG levels < 140 mg/dL, 535 of which were < 126 mg/dL. Of these patients, 200/1040 (19.2%) and 105/535 (19.6%) had DPN. Multivariate analysis demonstrated that higher HbA_1c levels (≥ 7%) did not increase risk of painless DPN, but did significantly increase risk of painful DPN in T2D patients with FPG < 140 mg/dL and < 126 mg/dL, with corresponding odds ratios of 2.49 and 3.77 (95% confidence intervals: 1.09–5.71 and 1.20–11.79), respectively, after adjusting for demographic factors, diabetes-related variables and comorbidities.ConclusionThis study is the first to reveal that increased postprandial glycaemic exposure, as assessed by high HbA1c and near-normal FPG levels, is associated with an increased risk of painful DPN in adults with T2D.     

Factors predictive of macrosomia in pregnancies with a positive oral glucose challenge test: Importance of fasting plasma glucose

AimThe study aimed to determine the factors associated with fetal macrosomia following a positive oral glucose challenge test (OGCT).MethodsIn this retrospective single-centre study of 1268 pregnancies with positive 50-g OGCTs (plasma glucose ≥ 130 mg/dL, or 7.2 mmol/L), gestational diabetes mellitus (GDM) was defined as fasting plasma glucose (FPG) ≥ 95 mg/dL (5.3 mmol/L) and/or postprandial glucose (PPG) ≥ 120 mg/dL (6.7 mmol/L).ResultsIn GDM pregnancies, the odds ratios adjusted for confounders (age, BMI, ethnicity, parity and weight gain) were 2.02 for macrosomia (Z score ≥ 1.28) and 2.62 for severe macrosomia (Z score ≥ 1.88). For each 10-mg/dL increase in FPG, the mean birth–weight increase was 60 g. Macrosomia risk did not differ between GDM patients with normal FPG (< 95 mg/dL, or 5.3 mmol/L) and non-diabetics, but increased significantly in cases of FPG ≥ 95 mg/dL and regardless of the level of PPG.ConclusionIn our study population, birth–weight and macrosomia risk were strongly correlated with FPG, suggesting that it is a simple and efficient marker for the risk of macrosomia.     

Accuracy assessment of online glucose monitoring by a subcutaneous enzymatic glucose sensor during exercise in patients with type 1 diabetes treated by continuous subcutaneous insulin infusion

AimOnline continuous glucose monitoring (CGM) during physical exercise would be highly useful in patients with insulin-treated diabetes. For this reason, this study assessed whether such a goal could be reached with a subcutaneous ‘needle-type’ enzymatic sensor.MethodsTen patients (five women/five men), aged 51 ± 12 years, with type 1 diabetes for 24 ± 11 years treated by continuous subcutaneous insulin infusion (CSII) for more than 1 year (HbA_1c: 7.5 ± 0.8%) performed a 30-min bout of exercise at a constant high-intensity load (15% above their individual ventilatory threshold) on a cycle ergometer. All patients wore a subcutaneous ‘needle-type’ enzymatic glucose sensor linked to a portable monitor (Guardian^® RT, Medtronic-MiniMed, Northridge, CA, USA) that had been inserted the previous evening. Sensor calibration was performed against capillary blood glucose immediately before the exercise. CGM values were recorded every 5 min from T_–10 to T₊₃₀, then every 10 min during the recovery period from T₊₃₀ to T₊₉₀. These recorded values were compared with blood glucose assays performed on simultaneously collected venous samples.ResultsSensor functioning and tolerability raised no problems except for one sensor that could not be adequately calibrated. Data from this patient were excluded from the data analysis. An average blood glucose decrease of 63 ± 63 mg/dL (3.5 ± 3.5 mmol/L) (median decrease: 58 mg/dL [3.22 mmol/L]; range: –3 mg/dL [0.16 mmol/L] to 178 mg/dL [9.8 mmol/L]) occurred during exercise bouts, while CGM values decreased by 38 ± 49 mg/dL (2.11 ± 2.72 mmol/L) (median: 32 mg/dL [1.7 mmmol/L]; range: –15 mg/dL [0.83 mmol/L] to 58 mg/dL [3.22 mmol/L]). Cumulative paired glucose values (n = 135) could be analyzed. The correlation factor between CGM and blood glucose values was 0.957 with an intercept of 0.275. The mean difference between paired values according to Bland–Altman analysis was 10 ± 31 mg/dL (0.56 ± 1.72 mmol/L). Clarke error grid analysis showed 91% of paired points in A and B zones, while 0%, 9% and 0% of paired points were in the C, D and E zones, respectively.ConclusionBlood glucose changes during intensive physical-exercise bouts performed by CSII-treated type 1 diabetes patients can be estimated with acceptable clinical accuracy by online CGM.     

Fenotipo de Cintura Hipertrigliceridémica en la población con Enfermedad Renal Crónica. Cohorte NEFRONA

Background and objectiveThe hypertriglyceridaemic waist (HTW) phenotype is defined for the general population. Chronic kidney disease (CKD) tends to bring on changes in body composition, is associated with higher comorbidity than the general population and, furthermore, shows reverse epidemiology with related prognostic variables like cholesterol and body mass index. Our objective was to identify cut-off points in the population with CKD and to analyse its relationship with cardiovascular risk (CVR).MethodsWe included 2271 CKD patients from the NEFRONA cohort. Triglyceride and waist cut-off points were selected through quintiles analysis and receiver operating characteristic (ROC) curves evaluation, using the presence of moderate to severe atherosclerosis score (AS 2-3) as outcome variable. Then, we analysed HTW prevalence and its association with other cardiovascular risk factors, and we measured the magnitude of its effect on AS 2-3 and cardiovascular event or death (CVEoD) by multivariate regression analysis.ResultsWe selected the cut-off points: triglyceride concentrations ≥143 mg/dl with waist circumference values >102 cm in men and 94 cm in women (sensitivity 26%; specificity 87%). Specific HTW prevalence was 22.4%, without significative differences between CKD stages. The multivariate regression analysis shows specific HTW as an independent AS 2-3 (OR 1.61; 95% CI: 1.12-2.32, p = 0.011) and CVEoD (HR 3.08; 95% CI: 1.66-5.72, p = 0.000) risk factor. An interaction between phosphorus level and specific HTW was identified.ConclusionsAdapting the HTW definition might improve specificity to assess cardiovascular risk in the population with CKD. It identifies an additional CVR in a population in which other screening methods have not proven to be useful, and it is easily clinically accessible. Its interaction with phosphorus levels suggests an association between HTW and bone-mineral metabolism regulation.     

Prognostic value of worsening renal function in outpatients with chronic heart failure

Introduction and objectivesRenal function impairment predicts poor survival in heart failure. Attention has recently shifted to worsening renal function, based mostly on serum creatinine and estimated glomerular filtration rate. We assessed the prognostic effect of worsening renal function in ambulatory heart failure patients.MethodsData from 306 ambulatory patients were abstracted from medical files. Worsening renal function was based on the change in estimated glomerular filtration rate, serum creatinine and urea within 6 months of referral. Prognosis was assessed by the composite endpoint all-cause death or heart failure hospitalization, censored at 2 years. Hazard ratios were estimated for worsening renal function, adjusted for sex, age, diabetes, New York Heart Association class, left ventricular systolic dysfunction, medications and baseline renal function.ResultsThe agreement among definitions was fair, with kappa coefficients generally not surpassing 0.5. Worsening renal function was associated with poor outcome with adjusted hazard ratios (95% confidence interval) of 3.2 (1.8–5.9) for an increase of serum creatinine > 0.3 mg/dl; 2.2 (1.3–3.7) for an increase in serum urea > 20 mg/dl and 1.9 (1.1–3.3) for a decrease in estimated glomerular filtration rate > 20%, independent of baseline renal function. The 2-year risk of death/heart failure hospitalization was approximately 50% in patients with an increase in serum creatinine or in serum urea; this positive predictive value was higher than for decreasing estimated glomerular filtration rate.ConclusionsIn conclusion, worsening renal function was significantly associated with a worse outcome. Different definitions identified different patients at risk and increasing creatinine/urea performed better than decreasing estimated glomerular filtration rate.     

Una puntuación de riesgo genético predice recurrencias en pacientes jóvenes con infarto agudo de miocardio

Introduction and objectivesTo evaluate whether a genetic risk score (GRS) improves prediction of recurrent events in young nondiabetic patients presenting with an acute myocardial infarction (AMI) and identifies a more aggressive form of atherosclerosis.MethodsWe conducted a prospective study with consecutive nondiabetic patients aged < 55 years presenting with AMI. We performed a genetic test, cardiac computed tomography, and analyzed several biomarkers. We studied the association of a GRS composed of 11 genetic variants and a primary composite endpoint (cardiovascular mortality, a recurrent event, and cardiac hospitalization).ResultsA total of 81 patients were studied and followed up for a median of 4.1 years. There were 24 recurrent cardiovascular events. Compared with the general population, study participants had a higher prevalence of 9 out of 11 risk alleles. The GRS was significantly associated with recurrent cardiovascular events, especially when baseline low-density lipoprotein cholesterol (LDL-C) levels were elevated. Compared with the low-risk GRS tertile, the multivariate-adjusted HR for recurrences was 10.2 (95%CI, 1.1-100.3; P = .04) for the intermediate-risk group and was 20.7 (2.4-181.0; P = .006) for the high-risk group when LDL-C was ≥ 2.8 mmol/L (≥ 110 mg/dL). Inclusion of the GRS improved the C-statistic (ΔC-statistic = 0.086), cNRI (continuous net reclassification improvement) (30%), and the IDI (integrated discrimination improvement) index (0.05). Cardiac computed tomography frequently detected coronary calcified atherosclerosis but had limited value for prediction of recurrences. No association was observed between metalloproteinases, GRS and recurrences.ConclusionsA multilocus GRS may identify individuals at increased risk of long-term recurrences among young nondiabetic patients with AMI and improve clinical risk stratification models, particularly among patients with high baseline LDL-C levels.     

Unexplained extreme hyperbilirubinemia among neonates in a multihospital healthcare system

We report a series of neonates who developed a total serum bilirubin (TSB) > 20 mg/dL during a recent ten-year period in a multihospital healthcare system. The incidence of a TSB > 20 mg/dL fell after instituting a pre-hospital discharge bilirubin screening program in 2003/2004 (91.3 cases/10,000 births before vs. 72.4/10,000 after), but the incidence has subsequently remained unchanged. No specific cause for the hyperbilirubinemia was identified in 66% of (n = 32) cases with a TSB > 30 mg/dL or in 76% of (n = 112) cases with a TSB 25.0–29.9 mg/dL. We hypothesized that hemolysis was a common contributing mechanism, but our review of hospital records indicated that in most instances these infants were not evaluated sufficiently to test this hypothesis. Records review showed maternal and neonatal blood types and direct antiglobulin testing were performed in > 95% cases, but rarely were other tests for hemolysis obtained. In the ten-year period reviewed there were zero instances where erythrocyte morphology from a blood film examination or Heinz body evaluation by a pediatric hematologist or pathologist were performed. In 3% of cases pyruvate kinase was tested, 3% were evaluated by hemoglobin electrophoresis, 3% had a haptoglobin measurement, and 16% were tested for G6PD deficiency. Thus, determining the cause for hyperbilirubinemia in neonates remains a problem at Intermountain Healthcare and, we submit, elsewhere. As a result, the majority of infants with a TSB > 25 mg/dL have no specific causation identified. We speculate that most of these cases involve hemolysis and that the etiology could be identified if searched for more systematically. With this in mind, we propose a “consistent approach” to evaluating the cause(s) of hyperbilirubinemia among neonates with a TSB > 25 mg/dL.     

Severe hypernatremia as a predictor of mortality after percutaneous endoscopic gastrostomy (PEG) placement

BackgroundPercutaneous endoscopic gastrostomy is the preferred option for providing enteral nutrition, allowing for an improvement in survival and quality of life.AimTo evaluate risk factors for early and delayed mortality after gastrostomy placement.MethodsA single-center retrospective analysis of a prospectively-collected database including all patients undergoing gastrostomy placement for enteral nutrition was performed. Two operators performed all the procedures according to the most recent guidelines.ResultsAnalysis included data on 438 patients [178 male; 80.5 (72–86) year-old]. Indications for PEG were stroke (34.0%), dementia (31.3%), neurodegenerative disorders (18.5%), coma (9.1%) and cancer (7.1%). No periprocedural adverse events was observed. Mean survival was 14.6 ± 3.4 months; 1-month and 3-month mortality rates were 4.0% and 8.1%, respectively. Severe hypernatremia (≥150 mmol/L) was independently related to 1-month mortality (odds ratio 25.4; P < 0.0001), while C-reactive protein level > 4.3 mg/dL was independently related to 3-month mortality (odds ratio 5.3; P = 0.003). Kaplan–Meier and Cox-regression analysis identified male gender (hazard ratio 2.32; P = 0.0002), severe hypernatremia (hazard ratio 4.3; P < 0.0001), C-reactive protein > 4.3 mg/dL (hazard ratio 3.5; P = 0.0014), leukocytosis (hazard ratio 1.97; P = 0.0036) and presence of underlying malignancy (hazard ratio 2.4; P = 0.0013) as independent risk factors for long-term mortality.DiscussionPresence of severe hypernatremia and increased C-reactive protein levels were strongly correlated with early and delayed mortality in our population. Studies are necessary to understand whether correcting underlying dehydration and inflammation further improves patients’ outcomes.     

Alirocumab efficacy and safety by body mass index: A pooled analysis from 10 Phase 3 ODYSSEY trials

AimsIncreased body mass index (BMI) contributes to cardiovascular risk and may influence efficacy of therapeutic antibodies. We investigated the effect of baseline BMI on efficacy and safety of alirocumab, a PCSK9 monoclonal antibody.MethodsIn a post-hoc analysis, data were pooled from 10 Phase 3 trials (n = 4975) of alirocumab vs. placebo/ezetimibe controls. Alirocumab dose was 150 mg every 2 weeks in two trials, and 75 mg every 2 weeks with possible increase to 150 mg at 12 weeks (based on Week 8 low-density lipoprotein cholesterol [LDL-C]) in eight trials. Efficacy/safety data were assessed in baseline BMI subgroups of ≤ 25, > 25 to 30, > 30 to 35, and > 35 kg/m².ResultsBaseline LDL-C levels were lower among patients in the higher BMI subgroups. Significant LDL-C reductions from baseline were observed at Weeks 12 and 24 for alirocumab vs. controls, of similar magnitude regardless of baseline BMI (interaction P-value = 0.7119). LDL-C < 1.81 mmol/L (< 70 mg/dL) was achieved at Week 24 by 69.8–76.4% of alirocumab-treated patients and 9.7–18.4% of control-treated patients, with no pattern by BMI. A greater proportion of patients in higher vs. lower BMI subgroups required alirocumab dose increase (P = 0.0343); proportions were 22.5%, 24.9%, 31.7%, and 27.2% of patients across BMI subgroups of ≤ 25, > 25 to 30, > 30 to 35, and > 35 kg/m², respectively. Adverse event frequencies were similar regardless of BMI; injection-site reaction frequency was higher with alirocumab (5.1–8.2% across BMI categories) vs. controls (3.6–4.8%).ConclusionsAlirocumab provided consistent LDL-C reductions, with similar safety findings across BMI subgroups.     

Modification of liver fibrosis,glucose and lipid profile after hepatitis C virus clearance with direct-acting antiviral agents

IntroductionThere is little information on whether direct-acting antiviral (DAA) treatment can improve liver fibrosis or change glucose and lipid profile in patients with chronic hepatitis C (CHC). We aimed to evaluate the impact of sustained virologic response (SVR) on liver stiffness, glucose and lipid levels.Methods445 monoinfected CHC patients started treatment with interferon-free DAA therapy from January 2015 to February 2017. Transient elastography (TE), fibrosis scores, glucose and lipid levels were analyzed at baseline and 48 weeks post-treatment (SVR48).ResultsThe SVR rate was 97.7%. Finally, we evaluated 369 patients who achieved SVR and had reliable TE measurements. Median liver stiffness significantly decreased from 9.3 (IQR 7.3–14.3) kPa at baseline to 6.4 (IQR 4.9–8.9) at SVR48 (p < 0.0001). 54.7% of the cohort presented fibrosis regression. Median FIB4 score regressed from 2.0 (IQR 1.1–3.3) to 1.3 (IQR 0.9–2.0) (p < 0.0001). Median APRI and Forns values significantly decreased from 0.9 (IQR 0.5–1.7) to 0.3 (IQR 0.2–0.4) and from 6.2 (5.0–7.5) to 4.9 (IQR 3.8–5.9) (p < 0.001), respectively. Mean levels of total cholesterol and LDL-C increased from 172 mg/dL and 101.5 mg/dL to 191 mg/dL and 117.5 mg/dL (p < 0.0001), respectively. In the sub-group of patients with pre-diabetes or diabetes, mean glucose levels decreased from 142.7 mg/dL at baseline to 127.2 mg/dL at SVR48 (p < 0.001).DiscussionSVR reduces liver stiffness based on TE and fibrosis scores, in patients treated with DAA. Our results show elevated total cholesterol and LDL-C and decreased glucose levels at SVR48.