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.

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.

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.

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.

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.

Acetazolamide and N-acetylcysteine in the treatment of chronic mountain sickness (Monge's disease).

Patients suffering from chronic mountain sickness (CMS) have excessive erythrocytosis. Low -level cobalt toxicity as a likely contributor has been demonstrated in some subjects. We performed a randomized, placebo controlled clinical trial in Cerro de Pasco, Peru (4380m), where 84 participants with a hematocrit (HCT) ≥65% and CMS score>6, were assigned to four treatment groups of placebo, acetazolamide (ACZ, which stimulates respiration), N-acetylcysteine (NAC, an antioxidant that chelates cobalt) and combination of ACZ and NAC for 6 weeks. The primary outcome was change in hematocrit and secondary outcomes were changes in PaO2, PaCO2, CMS score, and serum and urine cobalt concentrations. The mean (±SD) hematocrit, CMS score and serum cobalt concentrations were 69±4%, 9.8±2.4 and 0.24±0.15µg/l, respectively for the 66 participants. The ACZ arm had a relative reduction in HCT of 6.6% vs. 2.7% (p=0.048) and the CMS score fell by 34.9% vs. 14.8% (p=0.014) compared to placebo, while the reduction in PaCO2 was 10.5% vs. an increase of 0.6% (p=0.003), with a relative increase in PaO2 of 13.6% vs. 3.0%. NAC reduced CMS score compared to placebo (relative reduction of 34.0% vs. 14.8%, p=0.017), while changes in other parameters failed to reach statistical significance. The combination of ACZ and NAC was no better than ACZ alone. No changes in serum and urine cobalt concentrations were seen within any treatment arms. ACZ reduced polycythemia and CMS score, while NAC improved CMS score without significantly lowering hematocrit. Only a small proportion of subjects had cobalt toxicity, which may relate to the closing of contaminated water sources and several other environmental protection measures.

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.

Reverse Thermal Gel for In Utero Coverage of Spina Bifida Defects: An Innovative Bioengineering Alternative to Open Fetal Repair.

Current state-of-the-art management of open spina bifida defects entails an open fetal surgery approach associated with significant morbidities. In an attempt to reduce these risks and provide for an earlier minimally invasive repair, it is aimed to develop and characterize an innovative alternative using a unique reverse thermal gel. This study focuses on characterization of the physical and biological properties of the polymer and its in vivo applicability. Based on the knowledge and benchmarking, the "ideal" biomaterial should have the following characteristics: stability in amniotic fluid, limited permeability, biocompatibility, biologically functional, nontoxic, ability to support cellular functions, and in vivo applicability. The results demonstrate that the polymer possesses a unique ultrastructure, is stable in amniotic fluid, possesses limited yet predictable permeability, biocompatible with cells exposed in neural tube defects, is nontoxic, and can support cellular migration. These characteristics make it a potential novel alternative to open fetal repairs.

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.

Confidence in Assessment of Lumbar Spondylolysis Using Three-Dimensional Volumetric T2-Weighted MRI Compared With Limited Field of View, Decreased-Dose CT.

BACKGROUND: Limited z-axis-coverage computed tomography (CT) to evaluate for pediatric lumbar spondylolysis, altering the technique such that the dose to the patient is comparable or lower than radiographs, is currently used at our institution. The objective of the study was to determine whether volumetric 3-dimensional fast spin echo magnetic resonance imaging (3D MRI) can provide equal or greater diagnostic accuracy compared with limited CT in the diagnosis of pediatric lumbar spondylolysis without ionizing radiation. HYPOTHESIS: Volumetric 3D MRI can provide equal or greater diagnostic accuracy compared with low-dose CT for pediatric lumbar spondylolysis without ionizing radiation. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 2. METHODS: Three pediatric neuroradiologists evaluated 2-dimensional (2D) MRI, 2D + 3D MRI, and limited CT examinations in 42 pediatric patients who obtained imaging for low back pain and suspected spondylolysis. As there is no gold standard for the diagnosis of spondylolysis besides surgery, interobserver agreement and degree of confidence were compared to determine which modality is preferable. RESULTS: Decreased-dose CT provided a greater level of agreement than 2D MRI and 2D + 3D MRI. The kappa for rater agreement with 2D MRI, 2D + 3D MRI, and CT was 0.19, 0.32, and 1.0, respectively. All raters agreed in 31%, 40%, and 100% of cases with 2D MRI, 2D + 3D MRI, and CT. Lack of confidence was significantly lower with CT (0%) than with 2D MRI (30%) and 2D + 3D MRI (25%). CONCLUSION: For diagnosing spondylolysis, radiologist agreement and confidence trended toward improvement with the addition of a volumetric 3D MRI sequence to standard 2D MRI sequences compared with 2D MRI alone; however, agreement and confidence remain significantly greater using decreased-dose CT when compared with either MRI acquisition. CLINICAL RELEVANCE: Decreased-dose CT of the lumbar spine remains the optimal examination to confirm a high suspicion of spondylolysis, with dose essentially equivalent to radiographs. If clinical symptoms are not classic for spondylolysis, 2D MRI is still very good at detecting spondylolysis while remaining sensitive for detection of alternative diagnoses such as disc abnormalities and pars stress reaction. The data suggest that standard 2D MRI sequences should not be entirely replaced by a volumetric T2-weighted 3D sequence (despite promising features of rapid acquisition time, increased spatial resolution, and reconstruction capability).

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.

CT outperforms radiographs at a comparable radiation dose in the assessment for spondylolysis.

BACKGROUND: Lumbar spondylolysis, a unilateral or bilateral fracture at pars interarticularis, is a common cause of low back pain in children. The initial imaging study in the diagnosis of lumbar spondylolysis has historically been lumbar spine radiographs; however, radiographs can be equivocal or false-negative. Definitive diagnosis can be achieved with computed tomography (CT), but its use has been limited due to the dose of ionizing radiation to the patient. OBJECTIVE: By limiting the z-axis coverage to the relevant anatomy and optimizing the CT protocol, we are able to provide a definitive diagnosis of fractures of the pars interarticularis at comparable or lower radiation dose than commonly performed lumbar spine radiographs. As there is no gold standard for the diagnosis of spondylolysis besides surgery, we compared interobserver agreement and degree of confidence to determine which modality is preferable. MATERIALS AND METHODS: Sixty-two patients with low back pain ages 5-18 years were assessed for the presence of spondylolyis. Forty-seven patients were evaluated by radiography and 15 patients were evaluated by limited field-of-view CT. Both radiographic and CT examinations were assessed anonymously in random order for the presence or absence of spondylolyisis by six raters. Agreement was assessed among raters using a Fleiss Kappa statistic for multiple raters. RESULTS: CT provided a significantly higher level of agreement among raters than radiographs (P < 0.001). The overall Kappa for rater agreement with radiographs was 0.24, 0.34 and 0.40 for 2, 3 or 4 views, respectively, and 0.88 with CT. CONCLUSION: Interobserver agreement is significantly greater using limited z-axis coverage CT when compared with radiographs. Radiologist confidence improved significantly with CT compared to radiographs regardless of the number of views.

Stage of cirrhosis predicts the risk of liver-related death in patients with low Model for End-Stage Liver Disease scores and cirrhosis awaiting liver transplantation.

The Model for End-Stage Liver Disease (MELD) score has reduced predictive ability in patients with cirrhosis and MELD scores ≤ 20. We aimed to assess whether a 5-stage clinical model could identify liver transplantation (LT) candidates with low MELD scores who are at increased risk for death. We conducted a case-control study of subjects with cirrhosis and MELD scores ≤ 20 who were awaiting LT at a single academic medical center between February 2002 and May 2011. Conditional logistic regression was used to evaluate the risk of liver-related death according to the cirrhosis stage. We identified 41 case subjects who died from liver-related causes with MELD scores ≤ 20 within 90 days of death while they were waiting for LT. The cases were matched with up to 3 controls (66 controls in all) on the basis of the listing year, age, sex, liver disease etiology, presence of hepatocellular carcinoma, and MELD score. The cirrhosis stage was assessed for all subjects: (1) no varices or ascites, (2) varices, (3) variceal bleeding, (4) ascites, and (5) ascites and variceal bleeding. The MELD scores were similar for cases and controls. Clinical states contributing to death in cases were: sepsis 49%, spontaneous bacterial peritonitis 15%, variceal bleeding 24%, and hepatorenal syndrome 22%. In a univariate analysis, variceal bleeding [odds ratio (OR) = 5.6, P = 0.003], albumin (OR = 0.5, P = 0.041), an increasing cirrhosis stage (P = 0.003), reaching cirrhosis stage 2, 3, or 4 versus lower stages (OR = 3.6, P = 0.048; OR = 7.4, P < 0.001; and OR = 4.1, P = 0.008), a sodium level < 135 mmol/L (OR = 3.4, P = 0.006), and hepatic encephalopathy (OR = 2.3, P = 0.082) were associated with liver-related death. In a multivariate model including the cirrhosis stage, albumin, sodium, and hepatic encephalopathy, an increasing cirrhosis stage (P = 0.010) was independently associated with liver-related death. In conclusion, assessing the cirrhosis stage in patients with low MELD scores awaiting LT may help to select candidates for more aggressive monitoring or for living or extended criteria donation.

Sedation-related outcomes in postoperative management of pediatric laryngotracheal reconstruction.

OBJECTIVE: Examine outcomes of varied postoperative sedation management in pediatric patients recovering from single stage laryngotracheal reconstruction. DESIGN: Retrospective review of 34 patients treated with single stage laryngotracheal reconstruction from 2001 through 2011. SETTING: Tertiary children's hospital. METHODS: Patients were divided into 2 groups: those managed postoperatively with sedation, with or without paralysis (group 1), and those managed awake with narcotic pain medication as needed for primary management (group 2). Outcomes were measured as a function of sedation management. Outcomes investigated focused on those related to the success of the airway reconstruction, and those related to sedation management. RESULTS: Out of 68 cases of laryngotracheal reconstruction reviewed from 2001 to 2011, 34 were single stage reconstructions. Nineteen patients were sedated postoperatively (group 1) and fifteen patients were left awake (group 2). There were no significant differences between groups in airway-related outcomes, including risk of accidental decannulation, revision rates, and need for secondary airway procedures such as balloon dilation. Sedation-related outcomes, specifically focusing on differences in medical management, showed significant increases in rates of withdrawal (p<0.0001), nursing concerns of withdrawal (p<0.0001) and sedation level (p<0.0001), pulmonary complications (OR 7.7, p=0.008), and prolonged hospital stay due to withdrawal (p=0.0005) in patients managed with sedation with or without paralysis. Multivariable regression analysis revealed that duration of sedation was the primary risk factor for increased postoperative morbidity, while younger age, lower weight, and use of a posterior graft were also significant variables assessed. CONCLUSION: Avoiding sedation as the standard for postoperative management of single stage laryngotracheal reconstruction airway patients leads to an overall decreased risk of morbidity without increasing risk of airway-specific morbidity. This is specifically as related to withdrawal, pulmonary complications, concerns about sedation level and prolonged hospital course, all of which increase significantly with increased level and duration of sedation.

The impact of human leukocyte antigen mismatching on sensitization rates and subsequent retransplantation after first graft failure in pediatric renal transplant recipients.

BACKGROUND: U.S. allocation policies currently place less emphasis on human leukocyte antigen (HLA) matching in pediatric kidney transplant candidates to minimize dialysis time. The impact this may have on pediatric recipients after graft failure has not been extensively examined. METHODS: Using the Scientific Registry of Transplant Recipients database, we examined HLA sensitization after graft loss and regraft survival of all pediatric primary kidney transplant recipients younger than 18 years transplanted between 1990 and 2008, stratified by HLA-DR mismatch (MM) of first and second kidney transplant. RESULTS: Of 11,916 pediatric primary kidney transplant recipients, 2704 were relisted after first graft failure. 1847 received a retransplants, and 857 remained on the waiting list. Mean % panel reactive antibody increased from 6% to 45% for retransplant and from 8% to 76% for those on the waiting list. The degree of sensitization and waiting time to retransplantation increased with DR MM at first kidney transplantation. Two DR MM statuses at first transplant were associated with a 20% reduction in the hazard of receiving a retransplant (hazard ratio, 0.80 for 2 vs. 0-1 DR MM; P<0.001). Five-year retransplant graft survival was associated with the number of HLA MM at first and second kidney transplant. Retransplant graft survival was similar in the circumstance of a 0-1 DR MM living donor following a deceased donor, and the converse. CONCLUSION: In pediatric recipients, increasing number of initial HLA-DR MMs is associated with HLA sensitization, longer waiting time, decreased rate of retransplant, and decreased regraft survival. Consideration of DR matching at first transplant may mitigate these risks.

Differential effects of donor and recipient IL28B and DDX58 SNPs on severity of HCV after liver transplantation.

BACKGROUND & AIMS: IL28B single nucleotide polymorphisms are strongly associated with spontaneous HCV clearance and treatment response in non-transplant populations. A DDX58 single nucleotide polymorphism is associated with the antiviral response of innate lymphocytes. We aimed at evaluating the associations of donor and recipient IL28B (rs12979860 and rs8099917) and DDX58 (rs10813831) genotypes with severity of HCV recurrence after liver transplantation. METHODS: In a case-control study of 523 liver transplantation recipients with HCV, we matched severe with mild recurrent HCV based on 2-year clinical and histologic follow-up. A total of 440 liver transplantation recipients (severe, n=235; mild, n=205) with recipient DNA and 225 (severe, n=123; mild, n=102) with both recipient and donor DNA were analyzed. RESULTS: IL28B [rs12979860, non-CC (vs. CC) and rs8099917, non-TT (vs. TT)] in the recipient-only analysis had higher risk of severe recurrent HCV [OR 1.57 and 1.58, p<0.05]. However, for the 225 with donor and recipient DNA, IL28B rs12979860 CC (vs. non-CC) and rs8099917 TT (vs. non-TT) and DDX58 rs10813831 non-GG (vs. GG) were associated with more (not less) severe recurrent HCV. The greatest risk of severe recurrent HCV was for rs12979860 CC donors in non-CC recipients (OR 7.02, p <0.001, vs. non-CC donor/recipient) and for rs8099917 TT donors in non-TT recipients (OR 5.78, p=0.001, vs. non-TT donor/recipient). These associations persisted after controlling for donor age, donor race, and donor risk index. CONCLUSIONS: IL28B and DDX58 single nucleotide polymorphisms that are favorable when present in the non-transplant setting or in the recipient are unfavorable when present in a donor liver graft.

Projected future increase in aging hepatitis C virus-infected liver transplant candidates: a potential effect of hepatocellular carcinoma.

In the United States, the peak hepatitis C virus (HCV) antibody prevalence of 4% occurred in persons born in the calendar years 1940-1965. The goal of this study was to examine observed and projected age-specific trends in the demand for liver transplantation (LT) among patients with HCV-associated liver disease stratified by concurrent hepatocellular carcinoma (HCC). All new adult LT candidates registered with the Organ Procurement and Transplantation Network for LT between 1995 and 2010 were identified. Patients who had primary, secondary, or text field diagnoses of HCV with or without HCC were identified. There were 126,862 new primary registrants for LT, and 52,540 (41%) had HCV. The number of new registrants with HCV dramatically differed by the age at calendar year, and this suggested a birth cohort effect. When the candidates were stratified by birth year in 5-year intervals, the birth cohorts with the highest frequency of HCV were as follows (in decreasing order): 1951-1955, 1956-1960, 1946-1950, and 1941-1945. These 4 birth cohorts, spanning from 1941 to 1960, accounted for 81% of all new registrants with HCV. A 4-fold increase in new registrants with HCV and HCC occurred between the calendar years 2000 and 2010 in the 1941-1960 birth cohorts. By 2015, we anticipate that an increasing proportion of new registrants with HCV will have HCC and be ≥60 years old (born in or before 1955). In conclusion, the greatest demand for LT due to HCV-associated liver disease is occurring among individuals born between 1941 and 1960. This demand appears to be driven by the development of HCC in patients with HCV. During the coming decade, the projected increase in the demand for LT from an aging HCV-infected population will challenge the transplant community to reconsider current treatment paradigms.