Joshua Samuels

Improved Postoperative Outcomes Associated with Preoperative Statin Therapy

Statin therapy is well established for prevention of cardiovascular disease. Statins may also reduce postoperative mortality and morbidity via a pleiotropic (non–lipid-lowering) effect. The authors conducted a meta-analysis to determine the influence of statin treatment on adverse postoperative outcomes in patients undergoing cardiac, vascular, or noncardiovascular surgery. Two independent authors abstracted data from 12 retrospective and 3 prospective trials (n = 223,010 patients). A meta-analysis was performed to evaluate the overall effect of preoperative statin therapy on postoperative outcomes. Preoperative statin therapy was associated with 38% and 59% reduction in the risk of mortality after cardiac (1.9% vs. 3.1%; P = 0.0001) and vascular (1.7% vs. 6.1%; P = 0.0001) surgery, respectively. When including noncardiac surgery, a 44% reduction in mortality (2.2% vs. 3.2%; P = 0.0001) was observed. Preoperative statin therapy may reduce postoperative mortality in patients undergoing surgical procedures. However, the statin associated effects on postoperative cardiovascular morbidity are too variable to draw any conclusion.

Left Ventricular Hypertrophy in Hypertensive Adolescents Analysis of Risk by 2004 National High Blood Pressure Education Program Working Group Staging Criteria

The National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents recently recommended staging hypertension (HTN) in children and adolescents based on blood pressure severity. The use of blood pressure staging and its corresponding therapeutic approach was examined in this pooled analysis assessing the risk for end-organ damage, specifically left ventricular hypertrophy among hypertensive adolescents stratified by working group criteria. Newly diagnosed hypertensive adolescents and normotensive control subjects similar in age, race/ethnicity, gender, and body mass index completed casual and 24-hour ambulatory blood pressure measurements, M-mode echocardiography, and fasting serum laboratories. Hypertensive subjects had higher insulin and cholesterol but similar glucose levels as compared with control subjects. Among subjects with stage 1 HTN by casual blood pressure, 34% had white-coat HTN as opposed to 15% of stage 2 hypertensive subjects. Of the subjects with normal casual measurements, 20% had HTN by ambulatory monitoring. Subjects with stage 2 HTN by casual measurement alone (odds ratio: 4.13; 95% CI: 1.04 to 16.48) and after 24-hour ambulatory confirmation (odds ratio: 7.23; 95% CI: 1.28 to 40.68) had increased odds for left ventricular hypertrophy. In addition, the risk for left ventricular hypertrophy was similar for subjects with masked and confirmed stage 1 HTN, whereas subjects with white-coat HTN had a risk comparable to normotensive subjects. Thus, recommendations that adolescents with stage 2 HTN by casual measurements alone receive medication initially along with therapeutic lifestyle counseling are reasonable, though ambulatory blood pressure monitoring remains a valuable tool for evaluating children with stage 2 HTN, because >10% have white-coat HTN.

Masked Hypertension Associates with Left Ventricular Hypertrophy in Children with CKD

Left ventricular hypertrophy (LVH) associates with increased risk for cardiovascular disease. Hypertension leads to LVH in adults, but its role in the pathogenesis of LVH in children is not as well established. To examine left ventricular mass and evaluate factors associated with LVH in children with stages 2 through 4 chronic kidney disease (CKD), we analyzed cross-sectional data from children who had baseline echocardiography (n = 366) and underwent ambulatory BP monitoring (n = 226) as a part of the observational Chronic Kidney Disease in Children (CKiD) cohort study. At baseline, 17% of children had LVH (11% eccentric and 6% concentric) and 9% had concentric remodeling of the left ventricle. On the basis of a combination of ambulatory and casual BP assessment (n = 198), 38% of children had masked hypertension (normal casual but elevated ambulatory BP) and 18% had confirmed hypertension (both elevated casual and ambulatory BP). There was no significant association between LVH and kidney function. LVH was more common in children with either confirmed (34%) or masked (20%) hypertension compared with children with normal casual and ambulatory BP (8%). In multivariable analysis, masked (odds ratio 4.1) and confirmed (odds ratio 4.3) hypertension were the strongest independent predictors of LVH. In conclusion, casual BP measurements alone are insufficient to predict the presence of LVH in children with CKD. The high prevalence of masked hypertension and its association with LVH supports early echocardiography and ambulatory BP monitoring to evaluate cardiovascular risk in children with CKD.

Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents.

These pediatric hypertension guidelines are an update to the 2004 “Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents.” Significant changes in these guidelines include (1) the replacement of the term “prehypertension” with the term “elevated blood pressure,” (2) new normative pediatric blood pressure (BP) tables based on normal-weight children, (3) a simplified screening table for identifying BPs needing further evaluation, (4) a simplified BP classification in adolescents ≥13 years of age that aligns with the forthcoming American Heart Association and American College of Cardiology adult BP guidelines, (5) a more limited recommendation to perform screening BP measurements only at preventive care visits, (6) streamlined recommendations on the initial evaluation and management of abnormal BPs, (7) an expanded role for ambulatory BP monitoring in the diagnosis and management of pediatric hypertension, and (8) revised recommendations on when to perform echocardiography in the evaluation of newly diagnosed hypertensive pediatric patients (generally only before medication initiation), along with a revised definition of left ventricular hypertrophy. These guidelines include 30 Key Action Statements and 27 additional recommendations derived from a comprehensive review of almost 15 000 published articles between January 2004 and July 2016. Each Key Action Statement includes level of evidence, benefit-harm relationship, and strength of recommendation. This clinical practice guideline, endorsed by the American Heart Association, is intended to foster a patient- and family-centered approach to care, reduce unnecessary and costly medical interventions, improve patient diagnoses and outcomes, support implementation, and provide direction for future research.

Topical Rapamycin Therapy to Alleviate the Cutaneous Manifestations of Tuberous Sclerosis Complex A Double-Blind, Randomized, Controlled Trial to Evaluate the Safety and Efficacy of Topically Applied Rapamycin

Background and ObjectivesFacial angiofibromas are disfiguring facial lesions, present in up to 80% of patients with tuberous sclerosis complex. Recent elucidation of the complex cell signaling pathways that are disrupted in tuberous sclerosis indicates that rapamycin may be successful in alleviating the appearance of these lesions. The objectives of the current study were to evaluate the safety of topically applied rapamycin in patients with tuberous sclerosis complex and to determine its potential effectiveness in treatment of facial angiofibromas.Patients and MethodsThe study was a prospective, randomized, double-blind, placebo-controlled study performed at the University of Texas Health Science Center at Houston. Study subjects were recruited from the patient populations at the University of Texas Tuberous Sclerosis Center of Excellence. All subjects were over the age of 13 years and had a diagnosis of tuberous sclerosis complex. Subjects were excluded if they were using any form of rapamycin or if they were pregnant. Study subjects applied the study product to their facial angiofibromas nightly for a duration of 6 months. The investigational product contained one of three doses of rapamycin compounded with Skincerity®: (i) no rapamycin; (ii) 1 mg of rapamycin per 30 cc (0.003%); or (iii) 5 mg of rapamycin per 30 cc (0.015%). Plasma rapamycin concentrations were measured monthly to test for systemic absorption. Complete blood counts were performed monthly to test for anemia, neutropenia, or thrombocytopenia. Upon completion of the trial, subjects were asked if the formulation had improved the appearance of their facial angiofibromas.ResultsTwenty-three subjects completed the study. There was no detectable systemic absorption of rapamycin (all blood concentrations were <1.0 ng/mL). There were no significant changes in white blood cell, red blood cell, or platelet counts. Seventy-three percent of subjects in the treatment arms versus 38% of subjects in the placebo arm reported a subjective improvement in the appearance of their facial angiofibromas.ConclusionThe application of low-dose topical rapamycin (0.003–0.015%) to the face can safely decrease the appearance of facial angiofibromas in patients with tuberous sclerosis complex.Trial RegistrationClinicalTrials.gov Identifier: NCT01031901

Immunosuppressive treatments for immunoglobulin A nephropathy: A meta-analysis of randomized controlled trials

SUMMARY:  Immunoglobulin A (IgA) nephropathy is a worldwide disease that causes end‐stage kidney disease (ESRD) in up to 15–20% of affected patients within 10 years from the apparent onset of disease and in up to 30–40% of individuals within 20 years from diagnosis. No specific treatment has been established and there is wide variation in current practice. This systematic review evaluates the use of immunosuppressive agents to treat patients with IgA nephropathy. The Cochrane Renal Group Specialized Register, Cochrane Controlled Trial Registry, MEDLINE, EMBASE and article reference lists were searched for randomized or quasi randomized trials. Two independent reviewers assessed studies for inclusion criteria (biopsy proven IgA nephropathy, randomized trial, use of immunosuppressive agents) and extracted data regarding the effects of immunosuppressive agents on ESRD, doubling of serum creatinine, glomerular filtration rate, urinary protein excretion and side‐effects. Data were analysed with a random effects model. The published trials were few (13 trials, 623 patients) and were generally of poor quality. Compared with placebo, steroids were associated with a lower risk of progression to ESRD (six trials, 341 patients, RR 0.44, 95% CI 0.25–0.80) and lower end‐of‐trial proteinuria (six trials, 263 patients, weighted mean difference (WMD) −0.49 g/day, 95% CI −0.25 to −0.72). Treatment with alkylating agents significantly reduced end of treatment proteinuria (two trials, 122 patients, WMD −0.94, 95% CI −0.46 to −1.43). Although the optimal management of patients with IgA nephropathy remains uncertain because of limitations with the existing published data, immunosuppressive agents are a promising strategy and should be investigated further.

Ambulatory Blood Pressure Patterns in Children With Chronic Kidney Disease

Ambulatory blood pressure (BP) monitoring (ABPM) is the best method of detecting abnormal BP in patients with chronic kidney disease (CKD), whose hypertension may be missed with casual BP measurements. We report ABPM findings in 332 children 1 year after entry in the Chronic Kidney Disease in Children cohort study. All of the subjects underwent casual and ambulatory BP measurement. BP was categorized based on casual and ABPM results into normal (42%), white-coat (4%), masked (35%), and ambulatory (14%) hypertension. Only half of the subjects had a normal ABPM. BP load was elevated (>25%) in 52% (n=172), whereas mean BP was elevated in 32% (n=105). In multivariate analysis, those using an angiotensin-converting enzyme inhibitor were 89% more likely to have a normal ABPM than those who did not report using an angiotensin-converting enzyme inhibitor (odds ratio, 1.89 [95% CI, 1.17–3.04]). For every 20% faster decline in annualized glomerular filtration rate change, the odds of an abnormal ABPM increased 26% (odds ratio, 1.26 [95% CI, 0.97–1.64]). A 2.25-fold increase in urine protein:creatinine ratio annualized change was associated with a 39% higher odds of an abnormal ABPM (odds ratio, 1.39 [95% CI, 1.06–1.82]). Abnormalities on ABPM are common in children with chronic kidney disease and are strongly associated with known risk factors for end-stage renal disease. Individuals on angiotensin-converting enzyme inhibitors were less likely to have abnormal ABPM, suggesting a possible therapeutic intervention. ABPM should be used to monitor risk and guide therapy in children with chronic kidney disease.

Carotid Intima-Media Thickness in Children with CKD: Results from the CKiD Study

BACKGROUND AND OBJECTIVES In adults, increased carotid intima-media thickness (cIMT) as assessed by ultrasonography is a valid predictor of cardiovascular events. Children with CKD are known to be at increased cardiovascular risk. This study sought to identify cardiovascular risk factors associated with increased cIMT in children with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was a cross-sectional analysis of cIMT obtained after 12 months of follow-up of 101 children aged 2-18 years with mild to moderate CKD (median GFR 42.9 ml/min per 1.73 m(2)) in the Chronic Kidney Disease in Children cohort study enrolled between April 2005 and September 2009 and 97 healthy pediatric controls between January 2003 and December 2008. An average of six standardized B-mode ultrasound measurements constituted the overall cIMT measurement. RESULTS The median cIMT was 0.43 mm (interquartile range, 0.38-0.48) compared with 0.41 mm in healthy controls (P=0.03 for difference). After multivariable adjustment, the median cIMT was 0.02 mm (95% confidence interval [CI], 0.01-0.05) larger than that of the healthy controls. In a multivariable linear regression analysis, dyslipidemia and hypertension were associated with 0.05 mm (95% CI, 0.01-0.08) and 0.04 mm (95% CI, 0.003-0.08) greater mean cIMT, respectively. Body mass index, CKD etiology, GFR, birth weight, pubertal status, calcium, phosphorus, sex, and race were not associated with cIMT. CONCLUSIONS cIMT is significantly elevated among children with CKD, as is the prevalence of other cardiovascular risk factors. Of these risk factors, hypertension and dyslipidemia are significantly associated with increased cIMT.

Reliability of resting blood pressure measurement and classification using an oscillometric device in children with chronic kidney disease

OBJECTIVE To compare the reliability of blood pressure (BP) readings obtained with an oscillometric device with those obtained by auscultation and assess for differences in BP status classification based on the 2 techniques. STUDY DESIGN Resting BP was measured by auscultation and with an oscillometric device at the same encounter in 235 subjects enrolled in the Chronic Kidney Disease in Children study. Resting auscultatory BP values were averaged and compared with averaged oscillometric readings. BP agreement by the 2 methods was assessed using Bland-Altman plots, and BP status classification agreement was assessed by calculation of kappa statistics. RESULTS Oscillometric BP readings were higher than auscultatory readings, with a median paired difference of 9 mm Hg for systolic BP (SBP) and 6 mm Hg for diastolic BP (DBP). Correlation for mean SBP was 0.624 and for mean DBP was 0.491. The bias for oscillometric BP measurement was 8.7 mm Hg for SBP (P < .01) and 5.7 mm Hg for DBP (P < .01). BP status classification agreement was 61% for SBP and 63% for DBP, with Kappa values of .31 for SBP and .20 for DBP. CONCLUSIONS Compared with auscultation, the oscillometric device significantly overestimated both SBP and DBP, leading to frequent misclassification of BP status.

Effect of IV Contrast Medium on Renal Function in Oncologic Patients Undergoing CT in ICU

OBJECTIVE The purpose of our study was to assess the effect of IV contrast medium administered at CT on serum creatinine in an oncologic ICU population and to determine which of the variables before CT are most associated with renal function after administration of contrast material. MATERIALS AND METHODS We retrospectively reviewed 3,848 patient admissions to an oncology ICU. The following matched comparisons were undertaken: contrast-enhanced CT versus unenhanced CT and CT (with or without contrast medium) versus no CT. Matching criteria included age, sex, baseline serum creatinine, and severity of illness (modified sequential organ failure assessment [mSOFA] score). No patients with creatinine > 2.0 mg/dL received contrast material. Groups were compared using a rank sum test. Factors influencing creatinine after administration of contrast material were evaluated by multiple regression analysis. Parallel analyses using estimated glomerular filtration rate (eGFR) also were performed. RESULTS No significant difference was found in absolute change in creatinine between matched contrast-enhanced CT and unenhanced CT groups (n = 81), with mean (95% CI) creatinine rises after CT of 0.25 (0.04-0.46) and 0.11 (0.04-0.18) mg/dL, respectively. Similarly, for matched CT versus non-CT groups (n = 152), mean creatinine rises were 0.15 (0.05-0.25) and 0.12 (0.08-0.16) mg/dL, respectively. Parallel analyses using eGFR yielded similar results. Creatinine after administration of contrast material was associated with sex and mSOFA (p = 0.04 and 0.02, respectively) but not baseline creatinine. eGFR after administration of contrast material was associated with baseline eGFR (p < 0.0001). CONCLUSION Administration of IV contrast medium in oncologic ICU patients with relatively normal creatinine is associated with an increase in creatinine but not beyond that of simply undergoing CT or of a matched non-CT group in ICU. The eGFR, which includes sex in its derivation, may be a better predictor of contrast-enhanced renal function than creatinine.