Left ventricular dysfunction in Duchenne muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy is associated with progressive cardiorespiratory failure, including left ventricular dysfunction. METHODS AND RESULTS: Males with probable or definite diagnosis of Duchenne muscular dystrophy, diagnosed between 1 January, 1982 and 31 December, 2011, were identified from the Muscular Dystrophy Surveillance Tracking and Research Network database. Two non-mutually exclusive groups were created: patients with ≥2 echocardiograms and non-invasive positive pressure ventilation-compliant patients with ≥1 recorded ejection fraction. Quantitative left ventricular dysfunction was defined as an ejection fraction <55%. Qualitative dysfunction was defined as mild, moderate, or severe. Progression of quantitative left ventricular dysfunction was modelled as a continuous time-varying outcome. Change in qualitative left ventricle function was assessed by the percentage of patients within each category at each age. Forty-one percent (n = 403) had ≥2 ejection fractions containing 998 qualitative assessments with a mean age at first echo of 10.8 ± 4.6 years, with an average first ejection fraction of 63.1 ± 12.6%. Mean age at first echo with an ejection fraction <55 was 15.2 ± 3.9 years. Thirty-five percent (140/403) were non-invasive positive pressure ventilation-compliant and had ejection fraction information. The estimated rate of decline in ejection fraction from first ejection fraction was 1.6% per year and initiation of non-invasive positive pressure ventilation did not change this rate. CONCLUSIONS: In our cohort, we observed that left ventricle function in patients with Duchenne muscular dystrophy declined over time, independent of non-invasive positive pressure ventilation use. Future studies are needed to examine the impact of respiratory support on cardiac function.

Brachial Plexus Birth Injury: Epidemiology and Birth Weight Impact on Risk Factors.

BACKGROUND: Brachial plexus birth injury (BPBI) is a condition in which the brachial plexus is thought to be damaged during the birth process. Studies have cited a varying incidence rate ranging from 0.5 to 4.0 per 1000 live births. The purpose of this study is to evaluate birth claims data over a 15-year period to identify risk and protective factors for BPBI in the state of Colorado. METHODS: A data request was made to the state hospital association for birth claims data. We requested all birth claims from the years 2000 to 2014. ICD9 codes for variables of interest included: BPBI, shoulder dystocia, heavy-for-dates, macrosomia, breech delivery, instrumented birth, birth hypoxia, and gestational diabetes. A multivariable logistic regression model quantified both risk and protective factors for the development of BPBI as odds ratios (ORs) with 95% confidence intervals (CI). RESULTS: There were 966,447 birth records received from State Hospital Association. The BPBI incidence was 0.63/1000 live births. The mean (SD) birth weight was 3187 (572) g for the total population and 3808 (643) g for the BPBI births. Later admission year indicated a decrease in BPBI births (OR, 0.94; 95% CI: 0.92, 0.96/y). Asian, black, and Hispanic infants were more likely to have a BPBI than white infants. Shoulder dystocia (OR, 60.37; 95% CI: 47.90, 76.13) was the highest risk factor for BPBI followed by instrumented forceps birth (OR, 21.04; 95% CI: 12.22, 36.21), breech delivery (OR, 15.38; 95% CI: 5.60, 42.25), and gestational diabetes (OR, 4.46; 95% CI: 3.29, 6.57). Cesarean single births had the lowest risk for BPBI (0.27; 95% CI: 0.20, 0.37), whereas cesarean multiple births (2.33; 95% CI: 1.10, 4.94) and natural multiple births (3.20; 95% CI: 1.36, 7.55) were at higher risk when compared with natural single births and all were statistically significant at P<0.027. Colorado births had a decreased risk of BPBI compared with the United States each year from 2000 (0.82/1000 births vs. 1.6/1000 live births, P<0.001) to 2012 (0.56/1000 live births vs. 0.9/1000 live births, P=0.003). CONCLUSIONS: BPBI has decreased from 2000 to 2014. Historically Colorado has had a lower BPBI incidence than the United States. Shoulder dystocia, instrumented forceps birth, gestational diabetes, and breech delivery are the biggest predictors for BPBI. Increased awareness of shoulder dystocia and instrumented birth are hypothesized to have reduced these incidences. Nonwhites and Medicaid patients seem to be at higher risk for BPBI. LEVEL OF EVIDENCE: Level II-Prognostic.

Fassier-Duval Rod Failure: Is It Related to Positioning in the Distal Epiphysis?

BACKGROUND: The relationship between Fassier-Duval (FD) rod placement and rod failure rates has not previously been quantified. METHODS: Retrospective review was conducted on patients with osteogenesis imperfecta treated with FD rods between 2005 and 2017. Age at first surgery, sex, Sillence type of osteogenesis imperfecta, bisphosphonate treatment, location of rod (side of body and specific bone), and dates of surgeries, radiographs, and rod failures were collected. C-arm images determined rod fixation within the distal epiphysis at the time of surgery. C-arm variables included rod deviation (percent deviation from the midline of the distal epiphysis) and anatomical direction of deviation (anterior/posterior and medial/lateral). X-ray images were examined for rod failure, which was defined as bending, pulling out of the physis, protrusion out of the bone, and/or failure to telescope. Cox proportional hazards regression models were used to compare failure rates with location of placement within the distal epiphysis allowing for clustering of the data by side (left or right) and bone (femur or tibia). RESULTS: The cohort was 13 patients (11 female individuals and 2 male individuals) with a total of 66 rods and 75 surgeries. Mean time from the first surgery to the last follow-up visit was 8.9 years (SD=5 y). There was a 7% increase in hazard of failure per 1-mm increase in antero-posterior (AP) deviation [hazard ratio (HR), 1.07; 95% confidence interval (CI), 1.01-1.14; P=0.029)]. Similarly, there was a 9% increase in hazard of failure for every 1-mm increase in lateral deviation (HR, 1.09; 95% CI, 1.01-1.18; P=0.019). A 12% increase in hazard of failure per 10% increase in deviation from the midline for both AP and lateral radiograph views was also found, although this was only statistically significant for lateral deviation on the AP radiograph view (HR, 1.12; 95% CI, 1.01-1.25; P=0.030). CONCLUSIONS: FD rod placement within the distal epiphysis has significant impact on increasing rod survival. LEVEL OF EVIDENCE: Level III-therapeutic study.

The changing landscape of live kidney donation in the United States from 2005 to 2017.

The number of live kidney donors has declined since 2005. This decline parallels the evolving knowledge of risk for biologically related, black, and younger donors. To responsibly promote donation, we sought to identify declining low-risk donor subgroups that might serve as targets for future interventions. We analyzed a national registry of 77 427 donors and quantified the change in number of donors per 5-year increment from 2005 to 2017 using Poisson regression stratified by donor-recipient relationship and race/ethnicity. Among related donors aged <35, 35 to 49, and ≥50 years, white donors declined by 21%, 29%, and 3%; black donors declined by 30%, 31%, and 12%; Hispanic donors aged <35 and 35 to 49 years declined by 18% and 15%, and those aged ≥50 increased by 10%. Conversely, among unrelated donors aged <35, 35 to 49, and ≥50 years, white donors increased by 12%, 4%, and 24%; black donors aged <35 and 35 to 49 years did not change but those aged ≥50 years increased by 34%; Hispanic donors increased by 16%, 21%, and 46%. Unlike unrelated donors, related donors were less likely to donate in recent years across race/ethnicity. Although this decline might be understandable for related younger donors, it is less understandable for lower-risk related older donors (≥50 years). Biologically related older individuals are potential targets for interventions to promote donation.

A Simple Measure of Hepatocellular Carcinoma Burden Predicts Tumor Recurrence After Liver Transplantation: The Recurrent Hepatocellular Carcinoma-Initial, Maximum, Last Classification.

Risk of recurrent hepatocellular carcinoma (rHCC) after liver transplantation (LT) depends on the pre-LT HCC burden, tumor behavior, and response to locoregional therapy (LRT). In December 2017, LT priority for HCC was expanded to select patients outside the Milan criteria who respond to LRT. Our aims were to develop a novel objective measure of pre-LT HCC burden (model of recurrent hepatocellular carcinoma-initial, maximum, last [RH-IML]), incorporating tumor behavior over time, and to apply RH-IML to model post-LT rHCC. Using United Network for Organ Sharing data from between 2002-2014 (development) and 2015-2017 (validation), we identified adult LT recipients with HCC and assessed pre-LT HCC tumor behavior and post-LT rHCC. For each patient, HCC burden was measured at 3 points on the waiting list: initial (I), maximum (M) total tumor diameter, and last (L) exception petition. HCC burden at these 3 points were classified as (A) Milan to University of California, San Francisco (UCSF), and (D) >UCSF, resulting in each patient having a 3-letter RH-IML designation. Of 16,558 recipients with HCC, 1233 (7%) had any post-LT rHCC. rHCC rates were highest in RH-IML group CCC (15%) and DDD (18%). When M and L tumor burdens did not exceed Milan (class B or A), rHCC was low (≤10%) as in AAA, ABA, ABB, BBA, BBB; rHCC was also low (≤10%) with successful downstaging when L was A (

Comparison of a time-varying covariate model and a joint model of time-to-event outcomes in the presence of measurement error and interval censoring: application to kidney transplantation.

BACKGROUND: Tacrolimus (TAC) is an immunosuppressant drug given to kidney transplant recipients post-transplant to prevent antibody formation and kidney rejection. The optimal therapeutic dose for TAC is poorly defined and therapy requires frequent monitoring of drug trough levels. Analyzing the association between TAC levels over time and the development of potentially harmful de novo donor specific antibodies (dnDSA) is complex because TAC levels are subject to measurement error and dnDSA is assessed at discrete times, so it is an interval censored time-to-event outcome. METHODS: Using data from the University of Colorado Transplant Center, we investigated the association between TAC and dnDSA using a shared random effects (intercept and slope) model with longitudinal and interval censored survival sub-models (JM) and compared it with the more traditional interval censored survival model with a time-varying covariate (TVC). We carried out simulations to compare bias, level and power for the association parameter in the TVC and JM under varying conditions of measurement error and interval censoring. In addition, using Markov Chain Monte Carlo (MCMC) methods allowed us to calculate clinically relevant quantities along with credible intervals (CrI). RESULTS: The shared random effects model was a better fit and showed both the average TAC and the slope of TAC were associated with risk of dnDSA. The simulation studies demonstrated that, in the presence of heavy interval censoring and high measurement error, the TVC survival model underestimates the association between the survival and longitudinal measurement and has inflated type I error and considerably less power to detect associations. CONCLUSIONS: To avoid underestimating associations, shared random effects models should be used in analyses of data with interval censoring and measurement error.

Lower tacrolimus exposure and time in therapeutic range increase the risk of de novo donor-specific antibodies in the first year of kidney transplantation.

De novo donor-specific antibodies (dnDSAs) have been associated with reduced graft survival. Tacrolimus (TAC)-based regimens are the most common among immunosuppressive approaches used in in clinical practice today, yet an optimal therapeutic dose to prevent dnDSAs has not been established. We evaluated mean TAC C0 (tacrolimus trough concentration) and TAC time in therapeutic range for the risk of dnDSAs in a cohort of 538 patients in the first year after kidney transplantation. A mean TAC C0  < 8 ng/mL was associated with dnDSAs by 6 months (odds ratio [OR] 2.51, 95% confidence interval [CI] 1.32-4.79, P = .005) and by 12 months (OR 2.32, 95% CI 1.30-4.15, P = .004), and there was a graded increase in risk with lower mean TAC C0 . TAC time in the therapeutic range of <60% was associated with dnDSAs (OR 2.05, 95% CI 1.28-3.30, P = .003) and acute rejection (hazard ratio [HR] 4.18, 95% CI 2.31-7.58, P < .001) by 12 months and death-censored graft loss by 5 years (HR 3.12, 95% CI 1.53-6.37, P = .002). TAC minimization may come at a cost of higher rates of dnDSAs, and TAC time in therapeutic range may be a valuable strategy to stratify patients at increased risk of adverse outcomes.

Neutrophil-to-Lymphocyte Ratio Associates Independently With Mortality in Hospitalized Patients With Cirrhosis.

BACKGROUND & AIMS: The neutrophil to lymphocyte ratio (NLR) is a biomarker of immune dysregulation in patients with cirrhosis and is inexpensive to measure. We investigated the association between NLR and mortality in hospitalized patients with cirrhosis at 4 liver transplant centers, controlling for severity of acute-on-chronic liver failure (ACLF). METHODS: We performed a retrospective study using data from the North American Consortium for the Study of End-stage Liver Disease on patients with index hospitalizations for cirrhosis from December 2011 through December 2016. We collected data on patient demographics, NLR, model for end-stage liver disease (MELD) scores, serum levels of Na, cirrhosis stages, infections, hepatocellular carcinomas, and ACLF severity (based on number of organ failures). Competing risk regression analysis evaluated mortality within 1 year after hospital discharge, accounting for competing events (liver transplant). RESULTS: At admission, the patients' mean age was 57 years, mean MELD score was 21, and mean serum level of Na was 134 mmol/L. Sixty-eight patients had no organ failure, 21 patients had 1 organ failures, 7 patients had 2 organ failures, 4 patients had 3 organ failures, and 1 patient had 4 organ failures; 36% of the patients had confirmed or suspected infections. In univariate models, risk of death associated with increasing NLR, up to a value of 8 (hazard ratio [HR]= 1.14; 95% CI, 1.07-1.20; P < .001), and NLR quartile (for NLR range of 3-5, HR = 2.17; for NLR range of >5-9, HR=2.46; for NLR quartile >9, HR=2.84 vs the lowest quartile [NLR<3]) (P ≤ .001). The NLR remained statistically significant in multivariable models, adjusting for age, MELD score, hepatocellular carcinoma, and ACLF severity. Additionally, NLR was a statistically significant independent predictor of length of index hospital stay and mortality within 90 days after discharge. CONCLUSION: In a retrospective analysis of patients with cirrhosis, we found NLR to associate with death within 1 year after non-elective hospitalization. In these patients, the risk of death associated with acute immune dysregulation persists long after their initial hospitalization.

Safety of mTOR inhibitor continuation in pediatric heart transplant recipients undergoing surgical procedures.

mTOR inhibitors have been associated with SWC when used in the perioperative period. Limited literature is available to guide providers in managing chronic mTOR inhibitor use in the perioperative period, especially in the pediatric setting. The primary aim of this study was to describe the prevalence of SWC with mTOR inhibitor continuation during the perioperative period for major surgeries. Heart transplant recipients ≤25 years old at the time of primary heart transplant receiving sirolimus maintenance therapy during a surgical procedure and within the study period were included. Surgeries identified within the study period included otolaryngology procedures (46.2%), such as tonsillectomies with or without adenoidectomies, cardiac surgeries (30.8%) including a sternal revision, pulmonary vein repair, and pacemaker placement in two patients, orthopedic surgeries (15.4%) including a posterior spinal fusion and an Achilles tendon lengthening with ankle and subtalar joint release, and a neurosurgery (7.7%), which was a ventriculoperitoneal shunt revision. Thirteen surgical encounters were examined. One SWC was observed, an infected pacemaker requiring systemic antibiotics and removal of the device. The results of this study suggest that sirolimus may be continued in the perioperative period based on the low rate of SWC observed.

Oxybutynin 3% gel for the treatment of primary focal hyperhidrosis in adolescents and young adults.

BACKGROUND/OBJECTIVES: There are no reliably effective, well-tolerated topical agents for the treatment of hyperhidrosis. We sought to evaluate the efficacy and tolerability of oxybutynin 3% gel in adolescents and young adults with primary focal hyperhidrosis. METHODS: Patients with severe axillary hyperhidrosis were treated with topical oxybutynin 3% gel for 4 weeks. Response to treatment was assessed by calculating change in Hyperhidrosis Disease Severity Score from baseline to weeks 1 and 4. Change in health-related quality of life was assessed using the Children's Dermatology Life Quality Index or the Dermatology Life Quality Index. Adverse effects were evaluated using patient diaries, investigator global review, and physical examination. RESULTS: Of 10 patients aged 13-24 enrolled, seven completed the study. Of those who completed the study, four (57.1%) reported reduction in axillary Hyperhidrosis Disease Severity Score at week 1 and all seven (100%) at week 4. Six patients (85.7%) reported reduction in Children's Dermatology Life Quality Index or Dermatology Life Quality Index score. Anticholinergic adverse effects were infrequent. The majority of treatment-related adverse events were mild to moderate in severity. One patient experienced a severe adverse event. CONCLUSION: Oxybutynin 3% gel reduced hyperhidrosis severity and improved health-related quality of life in this small pilot study. Safety and efficacy should be further evaluated in a large, prospective, placebo-controlled study.

Neutrophil-to-lymphocyte ratio correlates with proinflammatory neutrophils and predicts death in low model for end-stage liver disease patients with cirrhosis.

The Model for End-Stage Liver Disease (MELD) score has reduced accuracy for liver transplantation (LT) wait-list mortality when MELD ≤ 20. Neutrophil-to-lymphocyte ratio (NLR) is a biomarker associated with systemic inflammation and may predict cirrhotic decompensation and death. We aimed to evaluate the prognostic utility of high NLR (≥4) for liver-related death among low MELD patients listed for LT, controlling for stage of cirrhosis. In a nested case-control study of cirrhotic adults awaiting LT (February 2002 to May 2011), cases were LT candidates with a liver-related death and MELD ≤ 20 within 90 days of death. Controls were similar LT candidates who were alive for ≥90 days after LT listing. NLR and other covariates were assessed at the date of lowest MELD, within 90 days of death for cases and within 90 days after listing for controls. There were 41 cases and 66 controls; MELD scores were similar. NLR 25th, 50th, 75th percentile cutoffs were 1.9, 3.1, and 6.8. NLR was ≥ 4 in 25/41 (61%) cases and in 17/66 (26%) controls. In univariate analysis, NLR (continuous ≥ 1.9, ≥ 4, ≥ 6.8), increasing cirrhosis stage, jaundice, encephalopathy, serum sodium, and albumin and nonselective beta-blocker use were significantly (P < 0.01) associated with liver-related death. In multivariate analysis, NLR of ≥1.9, ≥ 4, ≥ 6.8 were each associated with liver-related death. Furthermore, we found that NLR correlated with the frequency of circulating low-density granulocytes, previously identified as displaying proinflammatory properties, as well as monocytes. In conclusion, elevated NLR is associated with liver-related death, independent of MELD and cirrhosis stage. High NLR may aid in determining risk for cirrhotic decompensation, need for increased monitoring, and urgency for expedited LT in candidates with low MELD. Liver Transplantation 23 155-165 2017 AASLD.

Risk factors for bacteremia and central line-associated blood stream infections in children with acute myelogenous leukemia: A single-institution report.

BACKGROUND: Central line-associated blood stream infections (CLABSIs) are a source of high morbidity and mortality in children with acute myelogenous leukemia (AML). PROCEDURE: To understand the epidemiology and risk factors associated with the development of CLABSI in children with AML. METHODS: We retrospectively reviewed all patients with AML over a 5-year period between 2007 and 2011 at the Children's Hospital Colorado. Cases and controls were classified on the basis of the presence of a CLABSI as defined by the National Healthcare Safety Network. RESULTS: Of 40 patients in the study, 25 (62.5%) developed at least one CLABSI during therapy. The majority of CLABSIs were due to oral or gastrointestinal organisms (83.0%). Skin organisms accounted for 8.5%. In a multivariable analysis, the strongest risk factors associated with CLABSI were diarrhea (odds ratio [OR] 6.7, 95% confidence interval [CI] 1.6-28.7), receipt of blood products in the preceding 4-7 days (OR 10.0, 95%CI 3.2-31.0), not receiving antibiotics (OR 8.3, 95%CI 2.8-25.0), and chemotherapy cycle (OR 3.5, 95%CI 1.4-8.9). CLABSIs led to increased morbidity, with 13 cases (32.5%) versus two controls (1.9%) requiring transfer to the pediatric intensive care unit (P < 0.001). Three (7.5%) of 40 CLABSI events resulted in or contributed to death. CONCLUSIONS: Intensified line care efforts cannot eliminate all CLABSIs in the patients with AML. Exploring the role of mucosal barrier breakdown and/or the use of antibiotic prophylaxis may be effective strategies for further prevention of CLABSIs, supporting ongoing trials in this patient population.

Preprocedural Risk Assessment Prior to PPVI with CMR and Cardiac CT.

Percutaneous pulmonary valve intervention (PPVI) is a less invasive and less costly approach to pulmonary valve replacement compared with the surgical alternative. Potential complications of PPVI include coronary compression and pulmonary arterial injury/rupture. The purpose of this study was to characterize the morphological risk factors for PPVI complication with cardiac MRI and cardiac CTA. A retrospective review of 88 PPVI procedures was performed. 44 patients had preprocedural cardiac MRIs or CTAs available for review. Multiple morphological variables on cardiac MRI and CTA were compared with known PPVI outcome and used to investigate associations of variables in determining coronary compression or right ventricular-pulmonary arterial conduit injury. The most significant risk factor for coronary artery compression was the proximity of the coronary arteries to the conduit. In all patients with coronary compression during PPVI, the coronary artery touched the conduit on the preprocedural CTA/MRI, whilst in patients without coronary compression the mean distance between the coronary artery and the conduit was 4.9 mm (range of 0.8-20 mm). Multivariable regression analysis demonstrated that exuberant conduit calcification was the most important variable for determining conduit injury. Position of the coronary artery directly contacting the conduit without any intervening fat may predict coronary artery compression during PPVI. Exuberant conduit calcification increases the risk of PPVI-associated conduit injury. Close attention to these factors is recommended prior to intervention in patients with pulmonary valve dysfunction.

Association Between Plasma Level of Galectin-9 and Survival of Patients With Drug-Induced Acute Liver Failure.

BACKGROUND & AIMS: Fewer than 50% of patients with acute liver failure (ALF) recover spontaneously, and ALF has high mortality without liver transplantation. Kupffer cells have been reported to mediate liver inflammation during drug-induced injury. Galectin-9 is produced by Kupffer cells and has diverse roles in regulating immunity. We investigated whether plasma levels of galectin-9 are associated with outcomes of patients with ALF. METHODS: We analyzed plasma samples (collected at time of hospital admission) and clinical data from 149 patients included in the Acute Liver Failure Study Group from July 2006 through November 2010 (110 had acetaminophen-induced hepatotoxicity and 39 had nonacetaminophen drug-induced liver injury). We compared data with those from all patients enrolled in the study (from July 1, 2006 through October 30, 2013), and from healthy individuals of similar ages with no evidence of liver disease (control subjects). Plasma levels of galectin-9 were measured using a polyclonal antibody and colorimetric assay. RESULTS: Patients with ALF had statistically higher plasma levels of galectin-9 than control subjects, but levels did not differ significantly between patients with acetaminophen-induced liver injury and drug-induced liver injury. A level of galectin-9 above 690 pg/mL was associated with a statistically significant increase in risk for mortality or liver transplantation caused by ALF. Competing risk analyses associated level of galectin-9 with transplant-free survival, independently of Model For End-Stage Liver Disease score or systemic inflammatory response syndrome. CONCLUSIONS: A one-time measurement of plasma galectin-9 level can be used to assign patients with ALF to high-, intermediate-, and low-risk groups. The combination of galectin-9 level and Model For End-Stage Liver Disease score was more closely associated with patient outcome than either value alone. These data might be used to determine patient prognoses and prioritize patients for liver transplantation. ClinicalTrials.gov ID NCT00518440.

Predicting renal recovery after liver transplant with severe pretransplant subacute kidney injury: The impact of warm ischemia time.

Identifying which liver transplantation (LT) candidates with severe kidney injury will have a full recovery of renal function after liver transplantation alone (LTA) is difficult. Avoiding unnecessary simultaneous liver-kidney transplantation (SLKT) can optimize the use of scarce kidney grafts. Incorrect predictions of spontaneous renal recovery after LTA can lead to increased morbidity and mortality. We retrospectively analyzed all LTA patients at our institution from February 2002 to February 2013 (n = 583) and identified a cohort with severe subacute renal injury (n = 40; creatinine <2 mg/dL in the 14-89 days prior to LTA and not on renal replacement therapy [RRT] yet, ≥2 mg/dL within 14 days of LTA and/or on RRT). Of 40 LTA recipients, 26 (65%) had renal recovery and 14 (35%) did not. The median (interquartile range) warm ischemia time (WIT) in recipients with and without renal recovery after LTA was 31 minutes (24-46 minutes) and 39 minutes (34-49 minutes; P = 0.02), respectively. Adjusting for the severity of the subacute kidney injury with either Acute Kidney Injury Network or Risk, Injury, Failure, Loss, and End-Stage Kidney Disease criteria, increasing WIT was associated with lack of renal recovery (serum creatinine <2 mg/dL after LTA, not on RRT), with an odds ratio (OR) of 1.08 (1.01-1.16; P = 0.03) and 1.09 (1.01-1.17; P = 0.02), respectively. For each minute of increased WIT, there was an 8%-9% increase in the risk of lack of renal recovery after LTA. In a separate cohort of 98 LTA recipients with subacute kidney injury, we confirmed the association of WIT and lack of renal recovery (OR, 1.04; P = 0.04). In LT candidates with severe subacute renal injury, operative measures to minimize WIT may improve renal recovery potentially avoiding RRT and the need for subsequent kidney transplant. Liver Transplantation 22 1085-1091 2016 AASLD.

Effects of Anesthesia on Pediatric pH Impedance.

OBJECTIVES: Anesthesia can alter gastric and small intestinal motility, but its effect on gastroesophageal reflux (GER) is unclear. We set out to evaluate the effect of anesthesia on pH-multichannel intraluminal impedance (pH impedance) evaluation of GER. METHODS: Retrospective single-center analysis of 95 pH impedance probe studies performed in patients both with anesthesia exposure and esophagogastroduodenoscopy (n = 50) and without (n = 45). RESULTS: Increased acid reflux per hour, nonacid reflux per hour, and total reflux per hour were observed in the first 4 hours, both overall and in children 1 year or older and in both sedation groups. This difference remained for the older children without sedation by multiple regression analysis for nonacid reflux per hour and total reflux per hour. Patients using proton pump inhibitors had more nonacid reflux events per hour and total reflux events per hour regardless of sedation. CONCLUSIONS: Based on the results of the present study, there is no need to eliminate the data collected immediately after placement of the probe in children younger than 1 year of age, but in those who are 1 year or older without sedation, there may be a greater number of reflux events in the first 4 hours. The first 4 hours, therefore, should be carefully evaluated in patients older than 1 year of age. Further study is needed to provide normative data for the first 4 hours versus the later time period, both for those undergoing sedation and for unsedated patients, to validate the findings from the present study and to better understand the mechanism of GER.

Low, rather than high, body mass index confers increased risk for post-liver transplant death and graft loss: Risk modulated by model for end-stage liver disease.

With increasing attention being paid to optimizing patient outcomes, it has been proposed that liver transplantation (LT) for individuals with elevated body mass index (BMI) values and high Model for End-Stage Liver Disease (MELD) scores may adversely affect post-LT outcomes. We investigated the impact of BMI on post-LT outcomes in the context of MELD at LT. Using United Network for Organ Sharing data, we identified all adult (≥ 18 years) primary LT recipients from March 1, 2002 to September 30, 2011. BMI categories included the following: underweight, normal, overweight, class I obese, class II obese, and class III obese (<18.5; 18.5-24.9; 25-29.9; 30-34.9; 35-39.9; ≥ 40 kg/m(2), respectively). One-year post-LT death and graft loss were modeled using Cox regression, including interactions between BMI and MELD. A total of 45,551 adult recipients were identified: 68% male; median (interquartile range [IQR]) age 55 years (IQR, 49-60 years); MELD, 19 (IQR, 13-26); and donor risk index, 1.39 (IQR, 1.12-1.69). Representations in the BMI categories were underweight (n = 863, 2%), normal (n = 13,262, 29%), overweight (n = 16,329, 36%), class I obese (n = 9639, 21%), class II obese (n = 4062, 9%), and class III obese (n = 1396, 3%). In adjusted analyses, elevated BMI was not associated with increased risk for death or graft loss. Among the underweight, there were significant interactions between BMI and MELD with respect to death (P = 0.02) and graft loss (P = 0.01), with significantly increased risks for death (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.38-2.09; P = 0.006) and graft loss (HR, 1.45; 95% CI, 1.21-1.74; P = 0.02) among those with low MELD (≤ 26), compared to normal BMI recipients with low MELD. In conclusion, overweight and obese LT recipients do not have increased risk of death or graft loss regardless of MELD. Underweight patients are at increased risk for poor outcomes post-LT, specifically underweight recipients with low MELD have increased risk for death and graft loss. Mechanisms underlying this phenomenon warrant further investigation.

Optimizing repeat liver transplant graft utility through strategic matching of donor and recipient characteristics.

Repeat liver transplantation (LT) is controversial because of inferior outcomes versus primary LT. A minimum 1-year expected post-re-LT survival of 50% has been proposed. We aimed to identify combinations of Model for End-Stage Liver Disease (MELD), donor risk index (DRI), and recipient characteristics achieving this graft survival threshold. We identified re-LT recipients listed in the United States from March 2002 to January 2010 with > 90 days between primary LT and listing for re-LT. Using Cox regression, we estimated the expected probability of 1-year graft survival and identified combinations of MELD, DRI, and recipient characteristics attaining >50% expected 1-year graft survival. Re-LT recipients (n = 1418) had a median MELD of 26 and median age of 52 years. Expected 1-year graft survival exceeded 50% regardless of MELD or DRI in Caucasian recipients who were not infected with hepatitis C virus (HCV) of all ages and Caucasian HCV-infected recipients <50 years old. As age increased in HCV-infected Caucasian and non-HCV-infected African American recipients, lower MELD scores or lower DRI grafts were needed to attain the graft survival threshold. As MELD scores increased in HCV-infected African American recipients, lower-DRI livers were required to achieve the graft survival threshold. Use of high-DRI livers (>1.44) in HCV-infected recipients with a MELD score > 26 at re-LT failed to achieve the graft survival threshold with recipient age ≥ 60 years (any race), as well as at age ≥ 50 years for Caucasians and at age < 50 years for African Americans. Strategic donor selection can achieve >50% expected 1-year graft survival even in high-risk re-LT recipients (HCV infected, older age, African American race, high MELD scores). Low-risk transplant recipients (age < 50 years, non-HCV-infected) can achieve the survival threshold with varying DRI and MELD scores.

The corrected donor age for hepatitis C virus-infected liver transplant recipients.

Donor age has become the dominant donor factor used to predict graft failure (GF) after liver transplantation (LT) in hepatitis C virus (HCV) recipients. The purpose of this study was to develop and validate a model of corrected donor age (CDA) for HCV LT recipients that transforms the risk of other donor factors into the scale of donor age. We analyzed all first LT recipients with HCV in the United Network for Organ Sharing (UNOS) registry from January 1998 to December 2007 (development cohort, n = 14,538) and January 2008 to December 2011 (validation cohort, n = 7502) using Cox regression, excluding early GF (<90 days from LT). Accuracy in predicting 1 year GF (death or repeat LT) was assessed with the net reclassification index (NRI). In the development cohort, after controlling for pre-LT recipient factors and geotemporal trends (UNOS region, LT year), the following donor factors were independent predictors of GF, all P < 0.05: donor age (hazard ratio [HR], 1.02/year), donation after cardiac death (DCD; HR, 1.31), diabetes (HR, 1.23), height < 160 cm (HR, 1.13), aspartate aminotransferase (AST) ≥ 120 U/L (HR, 1.10), female (HR, 0.94), cold ischemia time (CIT; HR, 1.02/hour), and non-African American (non-AA) donor-African American (AA) recipient (HR, 1.65). Transforming these risk factors into the donor age scale yielded the following: DCD = +16 years; diabetes = +12 years; height < 160 cm = +7 years; AST ≥ 120 U/L = +5 years; female = -4 years; and CIT = +1 year/hour > 8 hours and -1 year/hour < 8 hours. There was a large effect of donor-recipient race combinations: +29 years for non-AA donor and an AA recipient but only +5 years for an AA donor and an AA recipient, and -2 years for an AA donor and a non-AA recipient. In a validation cohort, CDA better classified risk of 1-year GF versus actual age (NRI, 4.9%; P = 0.009) and versus the donor risk index (9.0%, P < 0.001). The CDA, compared to actual donor age, provides an intuitive and superior estimation of graft quality for HCV-positive LT recipients because it incorporates additional factors that impact LT GF rates.

Post-transplant survival is improved for hepatitis C recipients who are RNA negative at time of liver transplantation.

UNLABELLED: Hepatitis C virus (HCV) infection recurs universally in patients who are viremic at liver transplantation and likely accounts for the diminished post-transplant graft and patient survival. We evaluated whether undetectable HCV RNA pretransplant improves graft and patient survival after transplantation. Cases, defined by HCV listing diagnosis and positive HCV antibody, were selected from the Scientific Registry of Transplant Recipients database and further grouped as HCV RNA-positive (n = 4978) or negative (n = 445) based upon pretransplant testing. Controls were non-HCV recipients (n = 2995). RNA-negative cases had significantly better 5-year graft (72% vs. 64%) and patient (79% vs. 69%) survival than RNA-positive cases (P < 0.01 for both), and similar survival as controls (Graft: 72% vs. 74%, PATIENT: 79% vs. 80%; P > 0.05 for both). Nonproportional hazards modeling of RNA-positive cases identified a subgroup with rapid progression leading to early graft loss and death. Multivariable analyses confirmed that a positive HCV RNA prior to transplantation was a significant independent predictor of graft loss and death. In conclusion, HCV patients who have undetectable RNA at the time of liver transplantation experience improved long-term graft and patient outcomes. We speculate that the post-transplant survival of HCV recipients could be improved by safe and tolerable pretransplant antiviral strategies.