Impact of increasing operative time on the incidence of early failure and complications following free tissue transfer? A risk factor analysis of 2,008 patients from the ACS-NSQIP database.

BACKGROUND: There is a scarcity of externally valid data that investigate the utility of operative time, a common clinical parameter, as a predictor of free flap failures. Our aim was to assess whether prolonged operative time correlates with early flap failure following free tissue transfer in the acute care setting using the American College of Surgeons National Surgical Quality Improvement Program database. METHODS: The 2005-2011 American College of Surgeons National Surgical Quality Improvement Program databases were reviewed for encounters that entailed a free tissue transfer via a CPT algorithm. Patients identified as having a flap loss were compared with people who did not with regards to operative time and patient comorbidities. Patients were subdivided into the following cohort groups with regards to operative time: <6 hours, 6-12 hours, and >12 hours. Secondary outcome was association between increasing operative time and postoperative complications. RESULTS: Of the 2,008 patients identified, 62 (3.1%) had early flap failure. After multivariable analysis, it was found that progressive operative time was associated with an increased risk of flap failure; 6-12 hours odds ratio was 4.64 and >12 hours odds ratio was 5.65 (P = 0.0140). Higher American Society of Anesthesiologists class (P = 0.0042) was also shown to be significantly associated with flap failure. On secondary analysis, increasing operative time was correlated with the following complications: pneumonia, blood transfusions, prolonged ventilation, wound dehiscence, and wound complications. CONCLUSION: Our results, one of the largest series in the literature, revealed that prolonged operative time was associated with a stepwise increase in the likelihood of early flap failure as well certain postoperative complications. © 2014 Wiley Periodicals, Inc. Microsurgery 37:12-20, 2017.

Dialysis Patient Perspectives on CKD Advocacy: A Semistructured Interview Study.

BACKGROUND: Health advocacy groups provide education, raise public awareness, and engage in legislative, scientific, and regulatory processes to advance funding and treatments for many diseases. Despite a high burden of chronic kidney disease (CKD) in the United States, public awareness and research funding lag behind those for other disease states. We undertook this study of patients receiving maintenance dialysis to describe knowledge and beliefs about CKD advocacy, understand perceptions regarding advocacy participation, and elicit ideas for generating more advocacy in the dialysis community. STUDY DESIGN: Qualitative study. SETTING & PARTICIPANTS: 48 patients (89% response rate) receiving in-center hemodialysis (n=39), home hemodialysis (n=4), and peritoneal dialysis (n=5) from 14 US states. METHODOLOGY: Semistructured interviews. ANALYTICAL APPROACH: Transcripts were thematically analyzed. RESULTS: 5 themes describing patient perspectives on CKD advocacy were identified: (1) advocacy awareness (advocacy vs engagement knowledge, concrete knowledge, CKD publicity), (2) willingness to participate (personal qualities, internal efficacy, external efficacy), (3) motivations (altruism, providing a purpose, advancement of personal health, self-education), (4) resource availability (time, financial and transportation, health status), and (5) mobilization experience (key figure, mobilization network). Participants displayed operational understanding of advocacy but generally lacked knowledge about specific opportunities for participation. Personal qualities and external efficacy were perceived as important for advocacy participation, as were motivating factors such as altruism and self-education. Resources factored heavily into perceived participation ability. Most participants identified a key figure who invited them to participate in advocacy. In-person patient-delivered communication about advocacy opportunities was identified as critical to enhancing CKD advocacy among patients living on dialysis therapy. LIMITATIONS: Potential selection bias and inclusion of only English-speaking participants may limit generalizability. CONCLUSIONS: Overall, our results suggest that there may be untapped advocacy potential within the dialysis community and highlight the need for local in-person patient-led initiatives to increase patient involvement in CKD advocacy.

Effect of Continuous B Cell Depletion With Rituximab on Pathogenic Autoantibodies and Total IgG Levels in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

OBJECTIVE: To evaluate the effect of rituximab on pathogenic autoantibodies and total Ig levels, and to identify serious adverse events in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treated with continuous B cell depletion. METHODS: We conducted a retrospective analysis of 239 patients with AAV treated with rituximab-induced continuous B cell depletion. Two treatment cohorts were analyzed: an induction group (n = 52) and a maintenance group (n = 237). Changes in ANCA titers and total Ig levels over time were evaluated using mixed-effects models. Risk factors for serious infections during maintenance treatment were evaluated using Poisson regression. RESULTS: During induction, IgG levels fell at a mean rate of 6% per month (95% confidence interval [95% CI] 4, 8%), while ANCA levels declined at a mean rate of 47% per month (95% CI 42, 52%) and 48% per month (95% CI 42, 54%) for patients with antimyeloperoxidase (anti-MPO) antibodies and those with anti-proteinase 3 (anti-PR3) antibodies, respectively. During maintenance treatment, with a median duration of 2.4 years (interquartile range 1.5, 4.0 years), IgG levels declined a mean of 0.6% per year (95% CI -0.2, 1.4%). New significant hypogammaglobulinemia (IgG level of <400 mg/dl) during maintenance treatment occurred in 4.6% of the patients, all of whom were in the lowest baseline IgG quartile. Serious infections during maintenance therapy occurred at a rate of 0.85 per 10 patient-years (95% CI 0.66, 1.1) and were independently associated with an IgG level of <400 mg/dl. CONCLUSION: B cell-targeted therapy causes a preferential decline in ANCA titers relative to total IgG levels. Despite prolonged maintenance therapy with rituximab, IgG levels remain essentially constant. Serious infections were rare.

Serum phospholipid fraction of polyunsaturated fatty acids is the preferred indicator for nutrition and health status in hemodialysis patients.

Long chain (LC) polyunsaturated fatty acids (PUFA) are major components of cell membrane phospholipids (PL) and serve as precursors for numerous bioactive lipid derivatives. Fatty acids (FA) are routinely analyzed in biological samples to assess composition of tissues, cells, and lipid fractions. In human studies, serum or plasma is often used because of their easy procurement. However, the lipid pool in serum and plasma is a mixture of triacylglycerol (TG), PL, cholesterol and its esters, and other components. Herein, we report findings from a serum FA analysis after fractionation of polar and neutral lipids by solid phase extraction in a large cohort of 400 hemodialysis patients. LC PUFA were found concentrated in the polar fraction compared to the total or the neutral lipid fraction. When correlated with clinical markers of disease, a greater number of significant correlations were found for PUFA in polar compared to total or the neutral fraction. We also observed that polar lipids are a reliable reflection of LC PUFA status compared to the total or neutral fractions because the latter are diluted by non-essential FA. The relative amounts of LC PUFA in the total and neutral fractions reflect the contribution of TG in blood that varies with diet, age, and physiologic state. Our data indicate that LC PUFA in the polar fraction are superior indicators of bioactive FA-status than in the total or the neutral fraction and should be used to establish important links between PUFA status, their bioactive substrates in hemodialysis patients.

Ultrafiltration Rate and Mortality in Maintenance Hemodialysis Patients.

BACKGROUND: Observational data have demonstrated an association between higher ultrafiltration rates and greater mortality among hemodialysis patients. Prior studies were small and did not consider potential differences in the association across body sizes and other related subgroups. No study has investigated ultrafiltration rates normalized to anthropometric measures beyond body weight. Also, potential methodological shortcomings in prior studies have led to questions about the veracity of the ultrafiltration rate-mortality association. STUDY DESIGN: Retrospective cohort. SETTING & PARTICIPANTS: 118,394 hemodialysis patients dialyzing in a large dialysis organization, 2008 to 2012. PREDICTORS: Mean 30-day ultrafiltration rates were dichotomized at 13 and 10mL/h/kg, separately and categorized using various cutoff points. Ultrafiltration rates normalized to body weight, body mass index, and body surface area were investigated. OUTCOMES: All-cause mortality. MEASUREMENTS: Multivariable survival models were used to estimate the association between ultrafiltration rate and all-cause mortality. RESULTS: At baseline, 21,735 (18.4%) individuals had ultrafiltration rates > 13mL/h/kg and 48,529 (41.0%) had ultrafiltration rates > 10mL/h/kg. Median follow-up was 2.3 years, and the mortality rate was 15.3 deaths/100 patient-years. Compared with ultrafiltration rates ≤ 13mL/h/kg, ultrafiltration rates > 13mL/h/kg were associated with greater mortality (adjusted HR, 1.31; 95% CI, 1.28-1.34). Compared with ultrafiltration rates ≤ 10mL/h/kg, ultrafiltration rates > 10mL/h/kg were associated with greater mortality (adjusted HR, 1.22; 95% CI, 1.20-1.24). Findings were consistent across subgroups of sex, race, dialysis vintage, session duration, and body size. Higher ultrafiltration rates were associated with greater mortality when normalized to body weight, body mass index, and body surface area. LIMITATIONS: Residual confounding cannot be excluded given the observational study design. CONCLUSIONS: Regardless of the threshold implemented, higher ultrafiltration rate was associated with greater mortality in the overall study population and across key subgroups. Randomized controlled trials are needed to investigate whether ultrafiltration rate reduction improves clinical outcomes.

Longitudinal Changes in Protein Carbamylation and Mortality Risk after Initiation of Hemodialysis.

BACKGROUND AND OBJECTIVES: Carbamylation describes a post-translational protein modification associated with adverse outcomes in ESRD, but the risk implications of changes in carbamylation over time are not well understood. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We investigated the 1-year natural history of protein carbamylation in patients initiating maintenance hemodialysis and determined the prognostic value of longitudinal carbamylation changes in relation to mortality. In a nested patient-control study, we measured serial carbamylated albumin concentrations in select participants from a large incident dialysis cohort followed from 2004 to 2005 (n=10,044); 122 individuals who survived at least 90 days but died within 1 year of initiating hemodialysis (patients) were randomly selected along with 244 individuals who survived for at least 1 year (controls; matched for demographics). Carbamylated albumin concentration was measured using plasma collected at dialysis initiation and every subsequent 90-day period until 1 year or death. RESULTS: Baseline carbamylated albumin concentration was similar between controls and patients (mean±SD; 18.9±0.7 and 19.8±1.1 mmol/mol, respectively; P=0.94). From dialysis initiation to day 90, carbamylated albumin concentration markedly fell in all patients, with controls -9.9±0.8 mmol/mol (P<0.001) and patients -10.0±1.2 mmol/mol (P<0.001). Adjusted repeated measures analysis of carbamylated albumin concentration from dialysis initiation to 1 year or death showed that the mean change (95% confidence interval) in carbamylated albumin concentration from baseline to final measure differed significantly between groups (-9.3; 95% confidence interval, -10.8 to -7.7 for controls and -6.3; 95% confidence interval, -7.7 to -2.8 for patients; P<0.01). There were no such between-group differences in blood urea levels, Kt/V, or normalized protein catabolic rate. Mortality prediction assessed using c statistics showed that carbamylated albumin concentration, when modeled continuously as the difference from baseline to final, improved a fully adjusted model from 0.76 to 0.87 (P=0.03). CONCLUSIONS: Protein carbamylation decreased with dialysis initiation, and a greater reduction over time was associated with a lower risk for mortality. Carbamylation changes were able to predict individuals' mortality risk beyond traditional variables, including markers of dialysis adequacy and nutrition.

Racial Disparities in End-of-Life Communication and Preferences among Chronic Kidney Disease Patients.

BACKGROUND: Previous studies on end-of-life (EOL) care among patients with chronic kidney disease (CKD) have been largely limited to White hemodialysis patients. In this study, we sought to explore racial variability in EOL communication, care preferences and advance care planning (ACP) among patients with advanced CKD prior to decisions regarding the initiation of dialysis. METHODS: We performed a cross-sectional study between 2013 and 2015 of Black and White patients with stage IV or V CKD (per the Modified Diet in Renal Disease estimation of GFR <30 ml/min/1.73 m2) from 2 academic centers in Boston. We assessed experiences with EOL communication, ACP, EOL care preferences, hospice knowledge, spiritual/religious and cultural beliefs, and distrust of providers. RESULTS: Among 152 participants, 41% were Black. Black patients were younger, had less education, and lower income than White patients (all p < 0.01). Black patients also had less knowledge of hospice compared to White patients (17 vs. 61%, p < 0.01). A small fraction of patients (8%) reported having EOL discussions with their nephrologists and the majority had no advance directives. In multivariable analyses, Blacks were more likely to have not communicated EOL preferences (adjusted OR 2.70, 95% CI 1.08-6.76) and more likely to prefer life-extending treatments (adjusted OR 3.06, 95% CI 1.23-7.60) versus Whites. CONCLUSIONS: As Black and White patients with advanced CKD differ in areas of EOL communication, preferences, and hospice knowledge, future efforts should aim to improve patient understanding and promote informed decision-making.

Ultrafiltration Rates and the Quality Incentive Program: Proposed Measure Definitions and Their Potential Dialysis Facility Implications.

BACKGROUND AND OBJECTIVES: Rapid ultrafiltration rates are associated with adverse outcomes among patients on hemodialysis. The Centers for Medicare and Medicaid Services is considering an ultrafiltration rate quality measure for the ESRD Quality Incentive Program. Two measure developers proposed ultrafiltration rate measures with different selection criteria and specifications. We aimed to compare the proposed ultrafiltration rate measures and quantify dialysis facility operational burden if treatment times were extended to lower ultrafiltration rates. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data were taken from the 2012 database of a large dialysis organization. Analyses of the Centers for Medicare and Medicaid Services measure considered 148,950 patients on hemodialysis, and analyses of the Kidney Care Quality Alliance measure considered 151,937 patients. We described monthly patient and facility ultrafiltration rates and examined differences in patient characteristics across ultrafiltration rate thresholds and differences in facilities across ultrafiltration rate measure scores. We computed the additional treatment time required to lower ultrafiltration rates <13 ml/h per kilogram. RESULTS: Ultrafiltration rates peaked in winter and nadired in summer. Patients with higher ultrafiltration rates were younger; more likely to be women, nonblack, Hispanic, and lighter in weight; and more likely to have histories of heart failure compared with patients with lower ultrafiltration rates. Facilities had, on average, 20.8%±10.3% (July) to 22.8%±10.6% (February) of patients with ultrafiltration rates >13 ml/h per kilogram by the Centers for Medicare and Medicaid Services monthly measure. Facilities had, on average, 15.8%±8.2% of patients with ultrafiltration rates ≥13 ml/h per kilogram by the Kidney Care Quality Alliance annual measure. Larger facilities (>100 patients) would require, on average, 33 additional treatment hours per week to lower all facility ultrafiltration rates <13 ml/h per kilogram when total treatment time is capped at 4 hours. CONCLUSIONS: Ultrafiltration rates vary seasonally and across clinical subgroups. Extension of treatment time as a strategy to lower ultrafiltration rates may pose facility operational challenges. Prospective studies of ultrafiltration rate threshold implementation are needed.

Reduction of carbamylated albumin by extended hemodialysis.

Introduction Among conventional hemodialysis (CHD) patients, carbamylated serum albumin (C-Alb) correlates with urea and amino acid deficiencies and is associated with mortality. We postulated that reduction of C-Alb by intensive HD may correlate with improvements in protein metabolism and cardiac function. Methods One-year observational study of in-center nocturnal extended hemodialysis (EHD) patients and CHD control subjects. Thirty-three patients receiving 4-hour CHD who converted to 8-hour EHD were enrolled, along with 20 controls on CHD. Serum C-Alb, biochemistries, and cardiac MRI parameters were measured before and after 12 months of EHD. Findings EHD was associated with reduction of C-Alb (average EHD change -3.20 mmol/mol [95% CI -4.23, -2.17] compared to +0.21 [95% CI -1.11, 1.54] change in CHD controls, P < 0.001). EHD was also associated with increases in average essential amino acids (in standardized units) compared to CHD (+0.38 [0.08, 0.68 95%CI]) vs. -0.12 [-0.50, 0.27, 95% CI], P = 0.047). Subjects who reduced C-Alb more than 25% were found to have reduced left ventricular mass, increased urea reduction ratio, and increased serum albumin compared to nonresponders, and % change in C-Alb significantly correlated with % change in left ventricular mass. Discussion EHD was associated with reduction of C-Alb as compared to CHD, and reduction of C-Alb by EHD correlates with reduction of urea. Additional studies are needed to test whether reduction of C-Alb by EHD also correlates with improved clinical outcomes.

Time-specific placental growth factor (PlGF) across pregnancy and infant birth weight in women with preexisting diabetes.

OBJECTIVE: Determine the independent association between time-specific placental growth factor (PIGF)-a marker of placental vasculature-and infant birth weight in offspring of mothers with preexisting type 1 and 2 diabetes. METHODS: A total of 150 women were recruited from Joslin Diabetes Center's/Beth Israel Deaconess Medical Center's Diabetes in Pregnancy Program. PlGF was measured up to four times during pregnancy. Infant birth weight and covariate data were collected from medical records. Hemoglobin A1c was assessed from drawn blood samples. We used generalized linear and log-binomial models to calculate the change in continuous birth weight, as well as macrosomia for every unit change in time-specific ln-transformed PlGF, respectively. Models were adjusted for potential confounders. RESULTS: Approximately 75% of women had type 1 diabetes. Third trimester PlGF levels were significantly associated with infant birth weight (r = 0.24, p = 0.02 at 27-34 weeks; r = 0.26, p < 0.009 for 36-40 weeks). After full adjustment, there was a 6.1% and 6.6% increase in birth weight for gestational age percentile for each unit increase in ln-transformed PlGF level at 27-34 weeks and 35-40 weeks, respectively (95% CI for 27-34 weeks gestation: 1.1, 11.0, and 95% CI for 35-40 weeks gestation: 0.7%, 12.5%). We found a statistically significant increased risk of macrosomia among women with higher ln-transformed PlGF levels (RR: 1.72; 95% CI: 1.09, 2.70). Associations were not mediated by hemoglobin A1c. CONCLUSIONS: Third trimester PlGF levels were associated with higher birth weight in women with preexisting diabetes. These findings may provide insight to the pathophysiology of fetal overgrowth in women with diabetes.

Metabolomics of Chronic Kidney Disease Progression: A Case-Control Analysis in the Chronic Renal Insufficiency Cohort Study.

BACKGROUND: Whereas several longitudinal metabolomics studies have been conducted in individuals with normal estimated glomerular filtration rate (eGFR) at baseline, disease progression among individuals with established chronic kidney disease (CKD) has not been rigorously examined. METHODS: We performed a nested case-control study of rapid CKD progression in the Chronic Renal Insufficiency Cohort Study, profiling baseline plasma from 200 individuals each with eGFR slope <-3 ml/min/1.73 m2/year (cases) or between -1 and +1 ml/min/1.73 m2/year (controls), matched on baseline eGFR and proteinuria. To directly assess how the kidney modulates circulating metabolites, we profiled plasma from the aorta and renal vein of 25 hospital-based individuals. RESULTS: At baseline, cases and controls had a mean eGFR of 41.7 ± 13.3 and 45.0 ± 14.5 ml/min/1.73 m2, respectively. Ten plasma metabolites were nominally associated with CKD progression in logistic regression models adjusted for age, sex, race/ethnicity, hypertension, systolic and diastolic blood pressure, diabetes, eGFR and proteinuria; no metabolite achieved the Bonferroni-adjusted significance threshold (p < 0.0003). In a cross-sectional analysis, all 6 of the metabolites that were higher in cases than controls were significantly associated with eGFR at baseline. By contrast, threonine, methionine and arginine were lower in cases than in controls and had no association with baseline eGFR. Furthermore, in the hospital-based cohort that underwent renal arteriovenous sampling, these 3 metabolites were net released from the kidney. Combining these metabolites into a panel of markers further strengthened their association with CKD progression. CONCLUSION: Our results motivate interest in arginine, methionine and threonine as potential indicators of renal metabolic function and markers of renal prognosis.

Circulating Antiangiogenic Factors and Myocardial Dysfunction in Hypertensive Disorders of Pregnancy.

Hypertensive disorders of pregnancy (HDP) are associated with subclinical changes in cardiac function. Although the mechanism underlying this finding is unknown, elevated levels of soluble antiangiogenic proteins such as soluble fms-like tyrosine kinase-1 (sFlt1) and soluble endoglin (sEng) are associated with myocardial dysfunction and may play a role. We hypothesized that these antiangiogenic proteins may contribute to the development of cardiac dysfunction in HDP. We prospectively studied 207 pregnant women with HDP and nonhypertensive controls and evaluated whether changes in global longitudinal strain (GLS) observed on echocardiography is specific for HDP and whether these changes correlate with HDP biomarkers, sFlt1 and sEng. A total of 62 (30%) patients were diagnosed with preeclampsia (group A), 105 (51%) did not have an HDP (group B), and 40 (19%) were diagnosed with chronic or gestational hypertension (group C). Blood was drawn and sFlt1 and sEng levels measured using enzyme-linked immunosorbent assay. Comprehensive echocardiograms, including measurement of GLS, were performed on all patients. Overall, GLS was worse in women in group A (preeclampsia) than those in group B or C. Increasing sFlt1 and sEng levels correlated with worsening GLS (r=0.44 for sFlt1 and r=0.46 for sEng, both P<0.001), which remained significant after multivariable analysis (r=0.18 and r=0.22, both P≤0.01). Increasing levels also correlated with increasing left ventricular mass index, which also remained significant after multivariable analysis (r=0.20 for sFlt1 and 0.19 for sEng, both P=0.01). Elevated circulating levels of antiangiogenic proteins in HDP correlate with and may contribute to myocardial dysfunction as measured by GLS.

A Nationally Representative Study of Calcific Uremic Arteriolopathy Risk Factors.

Accurate identification of risk factors for calcific uremic arteriolopathy (CUA) is necessary to develop preventive strategies for this morbid disease. We investigated whether baseline factors recorded at hemodialysis initiation would identify patients at risk for future CUA in a matched case-control study using data from a large dialysis organization. Hemodialysis patients with newly diagnosed CUA (n=1030) between January 1, 2010, and December 31, 2014, were matched by age, sex, and race in a 1:2 ratio to hemodialysis patients without CUA (n=2060). Mean ages for patients and controls were 54 and 55 years, respectively; 67% of participants were women and 49% were white. Median duration between hemodialysis initiation and subsequent CUA development was 925 days (interquartile range, 273-2185 days). In multivariable conditional logistic regression analyses, diabetes mellitus; higher body mass index; higher levels of serum calcium, phosphorous, and parathyroid hormone; and nutritional vitamin D, cinacalcet, and warfarin treatments were associated with increased odds of subsequent CUA development. Compared with patients with diabetes receiving no insulin injections, those receiving insulin injections had a dose-response increase in the odds of CUA involving lower abdomen and/or upper thigh areas (odds ratio, 1.49; 95% confidence interval, 1.03 to 2.51 for one or two injections per day; odds ratio, 1.88; 95% confidence interval, 1.30 to 3.43 for 3 injections per day; odds ratio, 3.74; 95% confidence interval, 2.28 to 6.25 for more than three injections per day), suggesting a dose-effect relationship between recurrent skin trauma and CUA risk. The presence of risk factors months to years before CUA development observed in this study will direct the design of preventive strategies and inform CUA pathobiology.

KRYPTOR-automated angiogenic factor assays and risk of preeclampsia-related adverse outcomes.

OBJECTIVE: To evaluate KRYPTOR assays for circulating soluble fms-like tyrosine kinase-1 (sFlt1) and placental growth factor (PlGF) in risk assessment of adverse outcomes in women with suspected preeclampsia. METHODS: We studied 412 women carrying a singleton pregnancy from a previous study cohort who were evaluated for suspected preeclampsia. Another 434 nonpreeclamptic patients with plasma samples drawn throughout pregnancy were used to derive normative data. Plasma sFlt1 and PlGF levels were measured on the automated KRYPTOR platform and evaluated for prediction of adverse maternal and perinatal outcomes within 2 weeks. Normative values were used to create a ratio of markers and these values were reported as multiples of median (MoM) for women with and without adverse outcomes. The KRYPTOR assay results were also compared with previously reported measurements obtained using the automated Elecsys platform. RESULTS: Among participants presenting at <34 weeks (N = 110), patients with subsequent adverse outcome had higher sFlt1, lower PlGF, and higher sFlt1/PlGF ratio compared with women without adverse outcomes: the median (25th, 75th centile) sFlt1 (pg/ml), 9030 (3197, 12,140) versus 1976 (1248, 2937); PlGF (pg/ml), 36 (16, 111) versus 318 (108, 629); and ratio, 285.6 (32.2, 758.5) versus 6.1 (2.3, 20.3) (all p < 0.0001). Higher sFlt1/PlGF ratio correlated negatively with timing of delivery (r = -0.60, p < 0.001) and the risk of adverse outcomes was markedly elevated among women in highest tertile compared with lower tertile (odds ratio, 14.77; 95% confidence interval (CI), 4.28-51.00). The addition of sFlt1/PlGF ratio (≥85) to hypertension and proteinuria significantly improved the prediction for subsequent adverse outcomes (AUC 0.89 (95% CI): 0.82, 0.95) for hypertension, proteinuria, and sFlt1/PlGF (AUC = 0.75 (0.65, 0.85)) for hypertension alone (p = 0.002). Compared with normative controls, women who were evaluated for preeclampsia without adverse outcomes had higher MoM for sFlt1/PlGF ratio; these values were further elevated in women with adverse outcomes. sFlt1/PlGF ratios measured on the KRYPTOR platform were highly correlated with measurements obtained using Elecys platform (r = 0.97, p < 0.001). CONCLUSIONS: In women with suspected preeclampsia presenting prior to 34 weeks of gestation, KRYPTOR assays for circulating sFlt1 and PlGF when used in conjunction with standard clinical evaluation performs well in the prediction of adverse maternal and perinatal outcomes occurring within 2 weeks of presentation.

Changes in Kidney Function After Transjugular Intrahepatic Portosystemic Shunts Versus Large-Volume Paracentesis in Cirrhosis: A Matched Cohort Analysis.

BACKGROUND: Patients with cirrhosis and refractory ascites have physiologic and hormonal dysregulation that contributes to decreased kidney function. Placement of a transjugular intrahepatic portosystemic shunt (TIPS) can reverse these changes and potentially improve kidney function. We sought to evaluate change in estimated glomerular filtration rate (eGFR) following TIPS placement. STUDY DESIGN: Retrospective, matched cohort analysis. SETTINGS & PARTICIPANTS: Patients who underwent first-time TIPS placement for refractory ascites in 1995 to 2014. Frequency matching was used to generate a comparator group of patients with cirrhosis and ascites treated with serial large-volume paracentesis (LVP) in a 1:1 fashion. PREDICTOR: TIPS placement compared to serial LVP. OUTCOME: Change in eGFR over 90 days' follow-up. MEASUREMENTS: Multivariable regression stratified by baseline eGFR<60 versus ≥60mL/min/1.73m(2); analysis of effect modification between TIPS placement and baseline eGFR. RESULTS: 276 participants (TIPS, n=138; serial LVP, n=138) were analyzed. After 90 days, eGFRs increased significantly after TIPS placement in participants with baseline eGFRs<60mL/min/1.73m(2) compared to treatment with serial LVP (21 [95% CI, 13-29] mL/min/1.73m(2); P<0.001) and was no different in those with eGFRs≥60mL/min/1.73m(2) (1 [95% CI, -9 to 12] mL/min/1.73m(2); P=0.8). There was significant effect modification between TIPS status and baseline eGFR (P=0.001) in a model that included all participants. LIMITATIONS: Outcomes restricted by clinically recorded data; clinically important differences may still exist between the TIPS and LVP cohorts despite good statistical matching. CONCLUSIONS: TIPS placement was associated with significant improvement in kidney function. This was most prominent in participants with baseline eGFRs<60mL/min/1.73m(2). Prospective studies of TIPS use in populations with eGFRs<60mL/min/1.73m(2) are needed to evaluate these findings.

Sequential plasma angiogenic factors levels in women with suspected preeclampsia.

BACKGROUND: Alterations in circulating angiogenic factors are associated with the diagnosis of preeclampsia and correlate with adverse perinatal outcomes during the third trimester. OBJECTIVE: Analysis of the sequential levels of plasma angiogenic factors among patients admitted for evaluation of preeclampsia. STUDY DESIGN: We performed an observational study among women with singleton pregnancies admitted to Beth Israel Deaconess Medical Center, Boston, Massachusetts, for evaluation of preeclampsia at less than 37 weeks of gestation. Plasma samples were collected on admission and daily for the first 3 days and then weekly until delivery. Doppler ultrasound was performed on admission (within 48 hours) and then weekly (within 24 hours of blood collection) to evaluate uteroplacental and umbilical blood flows. Maternal demographics, hospital course, mode of delivery, diagnosis of hypertensive disorder, adverse maternal outcomes (elevated liver function enzymes, low platelet count, pulmonary edema, cerebral hemorrhage, convulsion, acute renal insufficiency, or maternal death), and adverse fetal/neonatal outcomes (small for gestational age, abnormal umbilical artery Doppler, fetal death, and neonatal death) were recorded. Circulating angiogenic factors (soluble fms-like tyrosine kinase and placental growth factor were measured on automated platform in a single batch after delivery and in a blinded fashion. Data are presented as median (25th to 75th centile), mean, or proportions as appropriate. RESULTS: During the study period, data from 100 women were analyzed for the study, and 43 had adverse outcomes. Women with adverse outcomes had lower gestational age of delivery, higher systolic and diastolic blood pressures during hospitalization, and lower birthweight and placental weight (all P < .01). These patients had higher soluble fms-like tyrosine kinase and soluble fms-like tyrosine kinase/placental growth factor ratio on admission and continued to have an increase in levels throughout hospital course. The median (25th to 75th) soluble fms-like tyrosine kinase/placental growth factor ratio among patients with adverse outcomes was 205.9 (72.5, 453.1) versus 47.5 (9.7, 87.0) among women without adverse outcomes (P < .001). The median (25th to 75th) absolute change per day in soluble fms-like tyrosine kinase levels (pg/mL) was 491.0 pg/mL (120.3, 1587.2) among women with adverse outcomes versus 81.3 pg/mL (-177.9, 449.0) among women without adverse outcomes (P = .01). Similarly the absolute change per day for soluble fms-like tyrosine kinase/placental growth factor ratio was 15.1 (1.8, 58.1) versus 2.7 (-0.6, 8.3) between the two groups (P = .004). The mean (range) days from admission to delivery was 6 (0-35) among subjects with soluble fms-like tyrosine kinase/placental growth factor ratio ≥85 and 14 (0-39) below a ratio of 85 (P < .001). The positive predictive value for plasma soluble fms-like tyrosine kinase/placental growth factor ratio ≥85 at admission for indicated delivery within 2 weeks was 91% (83-99%). Admission plasma soluble fms-like tyrosine kinase/placental growth factor ratio positively correlated with pre-delivery uterine artery resistive index (r = 0.35; P = .004). CONCLUSION: Among women admitted for evaluation of preeclampsia, women at risk for adverse pregnancy outcomes have higher soluble fms-like tyrosine kinase/placental growth factor ratio on admission, which continued to rise until delivery. Women with high soluble fms-like tyrosine kinase/placental growth factor ratios delivered sooner than women with low soluble fms-like tyrosine kinase/placental growth factor levels. These data support the hypothesis that targeting angiogenic imbalance in preeclampsia may lead to prolongation of pregnancy.

Relationship Between Comorbid Conditions and Utilization Patterns of Immediate Breast Reconstruction Subtypes Post-mastectomy.

There is limited information on the influence of a patient's comorbid status on the type of immediate breast reconstruction (IBR) selected. Our aim was to provide a population-based review of the relationship between baseline comorbid conditions and IBR subtype selected. This is a retrospective cohort study using the National Surgical Quality Improvement Program database to identify IBR recipients. Multivariable regression analyses was performed to identify the association between comorbidity and IBR subtype selection (prosthetic, pedicled, and free autologous). A total of 48,096 mastectomy patients were identified, of which 17,404 patients received IBR. IBR patients were younger (51 ± 10.4 versus 61.5 ± 13.6 years) and had a lower body mass index (27.1 ± 6.4 versus 28.9 ± 7.3) relative to patients who did not pursue IBR (p < 0.001 for all). Overall, IBR patients had a significantly lower incidence of comorbid conditions. In adjusted models, patients aged 45-64 years were more likely to pursue pedicled-autologous reconstruction (OR: 1.43, p < 0.001) and those older than 65 years were less likely to undergo free-autologous reconstruction (OR: 0.64, p = 0.02). Class I and II obesity was associated with pedicled (class I OR: 1.57, class II OR: 1.41) and free transfer (class I OR: 1.81, class II OR: 1.66) autologous IBR utilization (all p < 0.001). Also, smoking was related to increased chance of prosthetic reconstruction while preoperative radiotherapy was linked to free-autologous IBR. IBR patients were noted to be healthier than their non-IBR counterparts, and each IBR subtype was associated with a particular comorbidity profile. This has significant implications with regard to creation of an IBR-predictive model. Such a tool will improve preoperative counseling and decision making.

Hemodialysis arteriovenous fistula as first option not necessary in elderly patients.

OBJECTIVE: Kidney Disease Outcomes Quality Initiative guidelines recommend arteriovenous fistulas as the preferred access for hemodialysis patients. However, this may not hold across all populations of patients, especially the elderly, given their comorbidities and relatively reduced life expectancy. Therefore, we investigated whether fistulas held benefit over arteriovenous grafts as hemodialysis access in elderly patients. METHODS: We retrospectively searched a vascular access database to compare the outcomes for 138 fistulas and 44 grafts that were placed in elderly patients (≥75 years old) during a 4-year period at a tertiary medical center. RESULTS: The primary failure rate was higher for the fistulas compared with the grafts (odds ratio, 2.89; P = .008), and more fistulas required one or more interventions before their successful use compared with grafts (31% vs 10%, respectively; P = .03). In addition, the time to catheter-free dialysis was longer for fistulas than for grafts (P < .001). However, the primary and secondary patency rates were comparable between the fistulas and grafts and between the different access locations. The all-cause mortality rates were also comparable between the fistula and graft groups. CONCLUSIONS: Despite the Fistula First Initiative recommendations, grafts need not be discounted as a first-line hemodialysis access option in select elderly patients.

Removal of Soluble Fms-Like Tyrosine Kinase-1 by Dextran Sulfate Apheresis in Preeclampsia.

Preeclampsia is a devastating complication of pregnancy. Soluble Fms-like tyrosine kinase-1 (sFlt-1) is an antiangiogenic protein believed to mediate the signs and symptoms of preeclampsia. We conducted an open pilot study to evaluate the safety and potential efficacy of therapeutic apheresis with a plasma-specific dextran sulfate column to remove circulating sFlt-1 in 11 pregnant women (20-38 years of age) with very preterm preeclampsia (23-32 weeks of gestation, systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, new onset protein/creatinine ratio >0.30 g/g, and sFlt-1/placental growth factor ratio >85). We evaluated the extent of sFlt-1 removal, proteinuria reduction, pregnancy continuation, and neonatal and fetal safety of apheresis after one (n=6), two (n=4), or three (n=1) apheresis treatments. Mean sFlt-1 levels were reduced by 18% (range 7%-28%) with concomitant reductions of 44% in protein/creatinine ratios. Pregnancy continued for 8 days (range 2-11) and 15 days (range 11-21) in women treated once and multiple times, respectively, compared with 3 days (range 0-14) in untreated contemporaneous preeclampsia controls (n=22). Transient maternal BP reduction during apheresis was managed by withholding pre-apheresis antihypertensive therapy, saline prehydration, and reducing blood flow through the apheresis column. Compared with infants born prematurely to untreated women with and without preeclampsia (n=22 per group), no adverse effects of apheresis were observed. In conclusion, therapeutic apheresis reduced circulating sFlt-1 and proteinuria in women with very preterm preeclampsia and appeared to prolong pregnancy without major adverse maternal or fetal consequences. A controlled trial is warranted to confirm these findings.

Hypertension Risk Subsequent to Gestational Dysglycemia Is Modified by Race/Ethnicity.

Gestational diabetes mellitus is associated with an increased risk of type 2 diabetes mellitus and hypertension. Additionally, gestational dysglycemia has been associated with an increased risk of type 2 diabetes mellitus but not yet associated with hypertension subsequent to pregnancy in long-term follow-up. Therefore, we set out to examine this relationship as well as the role of race/ethnicity in modifying this relationship. We analyzed a prospective observational cohort followed between 1998 and 2007. There were 17 655 women with self-reported race/ethnicity and full-term, live births. A 1-hour 50 g oral glucose-load test and a 3-hour 100 g oral glucose-tolerance test enabled third trimester stratification of women into 1 of 4 glucose-tolerance groups: (1) normal (n=15 056); (2) abnormal glucose-load test (n=1558); (3) abnormal glucose-load and -tolerance tests (n=520); and (4) gestational diabetes mellitus (n=521). Women were then followed for a mean±standard deviation of 4.1±2.9 years after delivery for the development of hypertension. Although gestational diabetes mellitus was associated with an increased risk of hypertension after pregnancy (odds ratio [95% confidence interval]: 1.58 [1.02, 2.45]; P=0.04), dysglycemia defined by an abnormal glucose-load test predicted hypertension only among black women (4.52 [1.24, 16.52]; P=0.02). The risk of hypertension after pregnancy among dysglycemia groups not meeting criteria for gestational diabetes mellitus varied based on the race/ethnicity of the population. Further research on the implications of the intersection of race/ethnicity and gestational dysglycemia on subsequent hypertension is warranted.