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.

Tacrolimus Intrapatient Variability, Time in Therapeutic Range, and Risk of De Novo Donor-Specific Antibodies.

BACKGROUND: Tacrolimus (TAC) is the most important agent for maintenance immunosuppression and prevention of immunologic injury to the renal allograft, yet there remains no consensus on how best to monitor drug therapy. Both high TAC intrapatient variability and low TAC time in therapeutic range (TTR) have been associated with risk of de novo donor-specific antibodies (dnDSA). In this study, we hypothesized that the risk associated with high TAC coefficient of variation (CV) is a result of low TAC TTR rather than the variability itself. METHODS: We analyzed the risk of dnDSA, acute rejection, or death-censored graft loss by non-dosed-corrected TAC CV and TAC TTR during the first posttransplant year in a cohort of 538 patients with a median follow-up period of 4.1 years. RESULTS: Patients with CV >44.2% and TTR <40% (high intrapatient variability and low TTR) had a high risk of dnDSA (adjusted OR = 4.93, 95% confidence interval = 2.02-12.06, P < 0.001) and death-censored graft loss by 5 years (adjusted HR = 4.00, 95% confidence interval = 1.31-12.24, P = 0.015) when compared with patients with CV >44.2% and TTR ≥40% (high intrapatient variability and optimal TTR), while the latter patients had similar risk to patients with CV <44.2% (lower intrapatient variability). CONCLUSIONS: These data suggest that previously reported immunologic risk associated with high TAC intrapatient variability is due to time outside of therapeutic range rather than variability in and of itself when evaluating absolute non-dose-corrected TAC levels irrespective of reason or indication.

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.

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.

Establishment of a Medication Acuity Scoring Tool at a Tertiary Pediatric Teaching Hospital: A 2-Phase Process.

BACKGROUND: Currently, there is no validated objective rating system to address the acuity of medication orders that pharmacists review. OBJECTIVE: The objective was to assess the acuity of a given medication through creating and validating an acuity scoring tool. METHODS: Phase I included the development of the medication acuity scoring tool (MAST) from national safety standards and clinical experience. A survey was administered to pharmacists nationwide to establish a consensus on the individual components of the tool and their associated weighted scores. Phase II was designed to assess MAST's predictive validity by comparing a medication acuity rating generated by MAST to a rating assigned based upon clinical experience of experts. Additionally, in phase II, interrater and intrarater reliability of MAST was evaluated. RESULTS: In phase I, most of MAST's components and their associated scores achieved >75% agreement for inclusion in the final tool. In phase II, without MAST, approximately 50% of pharmacist-assigned acuity ratings were statistically consistent with tool-generated acuity ratings, and there was fair agreement between respondents (k=0.31). With the use of MAST, agreement in acuity ratings improved to substantial (k=0.69), and intrarater reliability was almost perfect (k=0.88). CONCLUSION: MAST is a validated rating system that captures the acuity of medications.

Potential Clinical Effects of a Novel Rapid Diagnostic Panel for Pediatric Musculoskeletal Infections.

A direct-from-source rapid musculoskeletal diagnostic panel (MDP) was validated recently. We compared clinical measures to theoretical time points had MDP results been available. The MDP would have significantly decreased the time to pathogen identification (7 hours), time to definitive antimicrobial therapy (22 hours), and hospital length of stay (26.4 hours).

Cosyntropin for the Treatment of Refractory Postdural Puncture Headache in Pediatric Patients: A Retrospective Review.

OBJECTIVES: Postdural puncture headache is a challenging complication of diagnostic, therapeutic, and unintentional lumbar puncture. Literature evidence supports cosyntropin as a viable noninvasive therapy for adults who have failed conservative management, but pediatric data are limited. The purpose of this retrospective chart review was to describe the use of intravenous cosyntropin for refractory pediatric postdural puncture headache at a single free-standing tertiary care pediatric hospital. METHODS: Patients who had received cosyntropin were identified. Charts were retrospectively reviewed for indication, dosing information, efficacy, and side effects. The response was defined as a 50% reduction in pain score, with a secondary efficacy measure of time to discharge after the first dose. RESULTS: Over a 5-year period, 26 patients received 37 doses of cosyntropin. Dosing ranged from 5 to 15 mcg/kg (median, 10.4 mcg/kg). There was a significant reduction in pain scores after the first dose of cosyntropin (P=0.008). Eighty-one percent of patients (n=21) achieved either a 50% reduction in pain or were discharged within 24 hours after the first dose. The median time to 50% pain reduction in 13 patients who achieved it before or discharge was 5 hours (range, 1 to 30 h). The median time to discharge after the first dose was 20 hours (range, 2 to 72 h). Ten patients received >1 dose of cosyntropin. Three patients required an epidural blood patch. No adverse effects related to treatment were identified. DISCUSSION: This study suggests that while further research is warranted, cosyntropin is a potential alternative to epidural blood patch for pediatric patients with postdural puncture headache who fail conservative management.

Relationship between bovine carotid artery grafts for hemodialysis access and human leukocyte antigen sensitization.

INTRODUCTION: Bovine carotid artery (BCA) Artegraft is a biologic graft that can be utilized as a conduit for permanent hemodialysis access and has been shown to outperform polytetrafluoroethylene grafts. However, concern regarding immunologic sensitization may limit the use of BCA in the transplant candidate. Panel reactive antibody (PRA) is an immunological test utilized in transplant recipient selection whereas increases in PRA limit access to transplantation. The purpose of our study was to determine whether BCA graft placement was adversely associated with increases in PRA. METHODS: Of patients listed for kidney transplant at our institution, we identified 10 patients who underwent BCA placement for hemodialysis access and a matched cohort of 10 patients who underwent native arteriovenous fistula (AVF) creation between 2014 and 2017. The PRA value nearest to the surgery date was compared to postsurgery PRA value for the BCA and AVF patients using a paired t test. Presurgery PRAs were also compared to the maximum PRA at 0 to 6, 6 to 12, 12 to 18, and 18 to 24 months postsurgery. FINDINGS: Prior to the dialysis access operation, the mean PRA was 14.1% ± 23.5% vs. 17.1% ± 29.0% (P = 0.76) and the median postsurgery follow-up time was 16 and 15 months for BCA and AVF cohorts, respectively. There were no statistically significant differences between presurgery and postsurgery PRA for BCA and AVF patients, regardless of time interval postsurgery. The difference in presurgery/postsurgery PRA change between cohorts was not statistically significant for PRAs closest to surgery (0.2% ± 40.6% vs. 1.0% ± 2.8%, P = 0.95, at a median 4 and 3 months postsurgery, respectively) or when using the maximum in any postsurgery interval. Prior to their dialysis access surgery, there were 16 sensitizing events in 5 patients in the BCA group compared to 10 events in 5 patients in the AVF group (P = 0.20). Only 1 of the 10 patients in the BCA group had a clinically relevant and sustained increase in PRA following their dialysis access operation vs. no patients in the AVF group (P > 0.99). However, this patient had a known sensitizing event (blood transfusion) between the BCA surgery and the postoperative PRA. Three of 10 patients in the BCA cohort vs. 5 of 10 patients in the AVF cohort went on to have successful kidney transplants (P = 0.65). DISCUSSION: The utilization of BCA for dialysis access was not associated with statistically significant changes in PRA. These data suggest that implantation of BCA will not affect access to organ transplantation.

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.

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 (

Cardiac allograft vasculopathy and graft failure in pediatric heart transplant recipients after rejection with severe hemodynamic compromise.

BACKGROUND: Rejection with severe hemodynamic compromise (RSHC) carries a mortality risk approaching 50%. We aimed to identify current risk factors for RSHC and predictors of graft failure after RSHC. METHODS: Data from 3,259 heart transplant (HT) recipients between January 2005 and December 2015 in the Pediatric Heart Transplant Study (PHTS) were analyzed. Predictors for RSHC and outcome after RSHC were sought. Time to RSHC was analyzed using the Cox proportional hazards regression model. Cardiac allograft vasculopathy (CAV) after HT and CAV after RSHC were analyzed as time-dependent covariates. Timing of RSHC was analyzed as occurring before and after 4 years after RSHC. RESULTS: There were 309 patients (9.5%) with ≥ 1 RSHC episodes. In 143 patients with RSHC, the first episode was within 1 year after HT. Independent risk factors for RSHC were age 1 to 5 years at HT (hazard ratio [HR], 1.51; 95% confidence interval [CI], 1.04-2.18), age > 10 years at HT (HR, 1.83; 95% CI, 1.29-2.60), black race (HR, 1.64; 95% CI, 1.25-2.15), prior cardiac surgery (HR, 1.55; 95% CI, 1.03-2.31), ventricular assist device support at HT (HR, 1.65; 95% CI, 1.18-2.29), maintenance steroids (HR, 1.39; 95% CI, 1.06-1.82), and recipient on inotropes, pressors, or thyroid hormones (HR, 1.45; 95% CI, 1.09-1.94). Graft survival at 5 years after RSHC was 45.7%. RSHC was a greater risk factor for earlier CAV (HR, 7.78; 95% CI, 5.82-10.40) than other rejection types (HR, 2.31; 95% CI, 1.79-3.00). Patients with late RSHC, after 1 year after RSHC had increased risk of graft loss 4 years after RSHC (HR, 7.12; 95% CI, 2.18-23.22). The 5-year graft survival after RSHC was 50.5% for early RSHC and 39.0% for late RSHC. CONCLUSIONS: Mortality after RSHC is high in the current treatment era. Many patient risk factors for RSHC cannot be modified, including age, race, prior cardiac surgery, and ventricular assist device support. After RSHC, CAV is the only predictor of graft failure. Patients who have late RSHC fare worse than those who have RSHC within the first year after HT.

Future Trends in Demand for Liver Transplant: Birth Cohort Effects Among Patients With NASH and HCC.

BACKGROUND: With increasing US adiposity, nonalcoholic steatohepatitis (NASH) is now a leading liver transplant (LT) indication. Given its association with hepatocellular carcinoma (HCC), the burden of NASH is substantial. We analyzed birth cohort effects among NASH LT registrants, with and without HCC. METHODS: All new LT registrants in United Network for Organ Sharing (1995-2015) were identified. Birth cohorts were defined as: 1936-1940, 1941-1945, 1946-1950, 1951-1955, 1956-1960, 1961-1965, 1966-1970, 1971-2015. Poisson regression examined trends in LT registration, by disease etiology (NASH, hepatitis C virus [HCV], other liver disease etiologies [OTHER]), and HCC. RESULTS: We identified 182 368 LT registrants with median age of 52 years (range, 0-86 years). Nine percent (n = 16 160) had NASH, 38% (n= 69 004) HCV, 53% (n = 97 204) OTHER. HCC was present in: 13% (n = 2181), 27% (n = 18 295), and 11% (n = 10 902), of NASH, HCV, and OTHER, respectively. Liver transplant registration for HCC increased significantly from 2002 to 2015 across all etiologies (NASH, 6%-18%; HCV, 19%-51%; OTHER, 9%-16%; P < 0.0001 for all). NASH LT registrations, with and without HCC, increased sharply in patients born from 1945 to 2015. This upward NASH trend is in stark contrast to HCV LT registrations, which showed a general decline. Notably, a sharp rise in LT registrations is occurring among younger NASH patients (35-55 years), mirroring the increasing adiposity across all age groups in the US population. CONCLUSIONS: NASH LT registrants, with and without HCC, have increased over time, and are projected to increase unabated in the future, notably among younger birth cohorts ("Adipose Wave Effect"). HCC LT registration patterns demonstrate that, compared with HCV, NASH patients encompass younger birth cohorts. These data illustrate that the full impact of NASH on demand for LT is yet to be realized.

Academic achievement and employment in young adults with end-stage kidney disease.

BACKGROUND: Young adults with end-stage kidney disease (ESKD) are at a pivotal stage of life: progressing through education, seeking employment and developing relationships. We set out to explore how ESKD impacts education and employment attainment in a matched UK and USA patient cohort. Moreover, we aimed to determine if there were significant differences in reported perceptions of impact. DESIGN: A mixed methods design combining previously validated quantitative questionnaire surveys and qualitative semi-structured interviews. PARTICIPANTS: Young people with ESKD aged 18-30 years (N = 27), attending single-centre follow-up in Oxford, UK were matched with 27 comparable young people aged 19-30 years, under follow-up in Denver, USA. Twelve of these patients from Denver were selected for interview. MEASUREMENTS: Self-report questionnaires surveyed patient demographics, educational and employment achievement and experiences. Questionnaire categorical data for matched pairs were analysed using Bowker's test of symmetry. Sequential flow analyses of interview content delineated perception patterns through thematic coding. RESULTS: Sixty percent of non-student Oxford participants were employed compared with 41% in Denver (p = 0.023). Forty-four percent of Oxford patients compared with 52% in Denver, reported illness had made it difficult to gain employment (p = 0.88). In Oxford, 32% completed high school as their highest educational achievement, versus 68% in Denver (p = 0.22). Qualitative themes included fatigue, self-esteem loss, social isolation and low mood. The impact of dialysis and poor understanding from educators/employers resulted in lost work time, and/or limited educational attainment. CONCLUSION: ESKD profoundly impacts on education and employment of young adults in the United States and United Kingdom, generating substantial barriers. Poor understanding appears prevalent amongst educators and employers. Healthcare providers must recognise these problems and invest resources towards tailored support in order to improve associated psychosocial and clinical 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.

A Vascular Anastomosis Simulation Can Provide a Safe and Effective Environment for Resident Skills Development.

OBJECTIVE: Vascular anastomoses are complex surgical procedures, performed in time-sensitive circumstances, making intraoperative teaching more challenging. We sought to evaluate whether a vascular anastomosis simulation was effective in developing resident skills. DESIGN, SETTING, PARTICIPANTS: General surgery residents participated in a vascular anastomosis simulation for 1 to 2hours during their transplant rotation. An attending transplant surgeon at the University of Colorado guided the resident through end-to-end and end-to-side anastomoses using bovine carotid artery (Artegraft). The residents completed a presimulation and postsimulation survey which quantitated their confidence. They also completed the MiSSES scale, which assessed the validity of the simulation. RESULTS: Twenty residents participated in the simulation and completed the surveys. The residents reported increased understanding in how to set up an end-to-end anastomosis and an end-to-side anastomosis (p = 0.001 and p = 0.009, respectively). They reported increased ability to suture, forehand and backhand with a Castro-Viejo needle driver (both p < 0.001). The residents reported increased ability to manipulate the needle (p = 0.006), and increased ability to manipulate tissue without causing trauma (p = 0.021). They reported increased confidence in tying a surgical knot with 6-0 Prolene and in operating while wearing loupes (p = 0.002, and p < 0.001, respectively). Overall, the residents reported increased confidence when asked to perform part of a vascular anastomosis in the operating room (p < 0.001). Seventeen residents completed the MiSSES scale with median scores of "somewhat agree" to "strongly agree" on all domains of the scale. CONCLUSIONS: The use of a simple, inexpensive vascular anastomosis simulation is an effective and safe environment to improve residents' surgical skills and the residents felt that the simulation was valid.

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.

De Novo Donor-Specific Antibody Formation in Tacrolimus-Based, Mycophenolate Versus Mammalian Target of Rapamycin Immunosuppressive Regimens.

OBJECTIVES: De novo donor-specific antibody formation posttransplant is associated with decreased graft survival. It is not known whether mammalian target of rapamycin inhibitors may be advantageous or detrimental compared with mycophenolate in the prevention of de novo donor-specific antibody formation. MATERIALS AND METHODS: We compared 66 kidney and kidney-pancreas transplant recipients who received tacrolimus, mammalian target of rapamycin inhibitor, and prednisone (group 1; 36 of whom received everolimus and 30 of whom received sirolimus) versus 132 patients who received tacrolimus, mycophenolate, and prednisone (group 2) matched for age, sex, race, and type/timing of transplant from 2007 to 2012. RESULTS: Rates of de novo donor-specific antibody formation were comparable between groups at 1, 6, and 12 months (16.7%, 25.8%, and 28.8% for group 1 vs 9.8%, 15.2%, and 22.0% for group 2). There were no significant differences in class (I, II, or mixed), strength (mean fluorescence intensity) of de novo donor-specific antibody, glomerular filtration rate, proteinuria levels, or acute rejection between the groups. In those with de novo donor-specific antibody by 6 months, acute rejection was more common versus those without de novo donor-specific antibody formation (24.3% vs 5.6% at 6 mo; P = .002), with rates of 27.0% versus 6.8% at 1 year (P = .001) and 40.7% versus 11.3% at 2 years (P < .001). An associated reduction in glomerular filtration rate also occurred. CONCLUSIONS: Mammalian target of rapamycin inhibitors were neither protective nor permissive for de novo donor-specific antibody formation versus mycophenolate when used with clinically relevant tacrolimus dosing regimens.

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.