Citations

Recipients of liver transplantation (LT) are at increased risk for symptomatic coccidioidomycosis, primarily because of chronic immunosuppression and impaired cellular immunity. Unfortunately, no consensus exists regarding optimal posttransplant prophylaxis. In a prior study at our institution, we observed both de novo and recurrent coccidioidomycosis despite targeted antifungal prophylaxis. In response, in February 2011, we instituted a universal prophylaxis program consisting of fluconazole (200 mg daily) for the first posttransplant year. In the current study, we retrospectively reviewed the medical records of all patients who underwent LT between the initiation of universal prophylaxis and July 11, 2013. Patients receiving a second transplant or dual‐organ transplant and those who died or did not have follow‐up in the 12‐month post‐LT period were excluded. Data from the universal prophylaxis cohort were compared with previously published data from the targeted prophylaxis era. Of the 160 patients undergoing LT during the study period, 143 met criteria for data analysis. When compared with the 349 patients in the targeted prophylaxis cohort, patients in the universal prophylaxis group were older and had higher rates of pre‐LT coccidioidomycosis, asymptomatic coccidioidal seropositivity, posttransplant diabetes mellitus, and renal insufficiency. Fluconazole‐related toxicity occurred in 13 of the universal prophylaxis patients, 7 of whom were required to discontinue use of the medication. Coccidioidomycosis developed in 10 of the 391 patients (2.6%) in the targeted prophylaxis cohort and in none of the patients in the universal prophylaxis group (P = 0.04). These data strongly support the use of a 1‐year antifungal prophylaxis regimen for LT recipients in endemic regions.Liver Transpl 21:353–361, 2015. © 2015 AASLD.

Key PointsIn this first ALL GWAS in AYAs, we determined that inherited GATA3 variants strongly influence ALL susceptibility in this age group. These findings revealed similarities and differences in the genetic basis of ALL susceptibility between young children and AYAs.

AbstractSarcopenia, or loss of skeletal muscle mass, is associated with increased mortality and morbidity in liver transplant (LT) candidates. Six‐minute walk distance (6MWD) and health‐related quality of life (HRQOL) as assessed by short form 36 scores (SF‐36) also impact clinical outcomes in these patients. This study explored the relationship between the sarcopenia, 6MWD, and HRQOL in LT candidates. Sarcopenia was evaluated based on skeletal muscle mass index (SMI) quantified from abdominal computed tomography. Patients were followed until death, removal from the wait list or the end of the study period. Two hundred and thirteen patients listed for LT were included. The mean SMI, 6MWD and mean gait speed were 54.3 ± 9.7, 370.5 m and 1 m/s, respectively. Sarcopenia was noted in 22.2% of LT candidates. There was no correlation between sarcopenia, 6MWD, and SF‐36 scores. The 6MWD, but not sarcopenia, was an independent predictor of mortality (hazard ratio = 2.1 [0.9–4.7]). In summary, sarcopenia did not emerge as a significant predictor of waitlist mortality and also failed to correlate with either functional capacity or HRQOL in LT candidates. In patients with ESLD awaiting LT, 6MWD appears to be a more useful prognostic indicator than the presence of sarcopenia.

Abstract Objective To examine the association of serum inflammatory markers (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) and serum lipid measures (low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol) with risk of myocardial infarction (MI) and ischaemic stroke (IS) among rheumatoid arthritis (RA) patients. Methods We conducted a retrospective cohort study using 2005–2010 data from a US commercial health plan. Eligible patients had two or more physician diagnoses of RA during a baseline period of at least 180 days with continuous medical and pharmacy coverage. We computed age-adjusted incidence rates of MI and IS, and used spline regression to assess non-linear associations and Cox-regression to quantify the independent association between the laboratory values and the outcomes. Results We identified 44 418 eligible RA patients (mean age 49 years; 76% women). CRP>10 mg/L compared with <1 mg/L was associated with increased MI risk (HR 2.12; 95% CI 1.02 to 4.38). ESR>42 mm/h compared with <14 mm/h was associated with increased risk of MI (HR 2.53; 95% CI 1.48 to 4.31) and IS (HR 2.51; 95% CI 1.33 to 4.75) risk. HDL-cholesterol ≥60 mg/dL (1.6 mmol/L) compared with <40 mg/dL (1.0 mmol/L) was associated with reduced MI risk (HR 0.37; 0.21 to 0.66). The association between LDL and MI was not linear; the lowest risk was observed among patients with LDL between 70 mg/L (1.8 mmol/L) and 100 mg/L (2.6 mmol/L). We did not observe a significant association between LDL and IS. Conclusions This study provides evidence supporting the hypothesis that RA-related systemic inflammation plays a role in determining cardiovascular risk and a complex relationship between LDL and cardiovascular risk.

The majority of intermediate‐risk rhabdomyosarcoma (RMS) patients have gross residual disease (Group III) after their first operative procedure. It is currently not known if local control rates can be maintained when, following induction chemotherapy, the radiation therapy (RT) dose is decreased after a delayed primary excision (DPE). To answer this question we evaluated patients enrolled on COG D9803 (1999–2005) who had Group III tumors of the bladder dome, extremity or trunk (thorax, abdomen and pelvis) were candidates for DPE at Week 12 if the primary tumor appeared resectable. RT dose was then adjusted by the completeness of DPE: no evidence of disease 36 Gy, microscopic residual 41.4 Gy and gross residual disease (GRD) 50.4 Gy. A total of 161 Group III patients were evaluated (24 bladder dome, 63 extremity and 74 trunk). Seventy‐three patients (45%) underwent DPE which achieved removal of all gross disease in 61 (84%) who were then eligible for reduced RT dose (43/73 received 36 Gy, 19/73 received 41.4 Gy). The local 5‐year failure rate (0% for bladder dome, 7% for extremity and 20% for trunk) was similar to IRS‐IV, which did not encourage DPE and did not allow for DPE adapted RT dose reduction. In conclusion, DPE was performed in 45% of Group III RMS patients with tumors at select anatomic sites (bladder dome, extremity and trunk) and 84% of those who had DPE were eligible for RT dose reduction. Local control outcomes were similar to historic results with RT alone.

Background: To assess whether the individual housing-based socioeconomic status (SES) measure termed HOUSES was associated with post-myocardial infarction (MI) mortality. Methods: The study was designed as a population-based cohort study, which compared post-MI mortality among Olmsted County, Minnesota, USA, residents with different SES as measured by HOUSES using Cox proportional hazards models. Subjects’ addresses at index date of MI were geocoded to real property data to formulate HOUSES (a z-score for housing value, square footage, and numbers of bedrooms and bathrooms). Educational levels were used as a comparison for the HOUSES index. Results: 637 of the 696 eligible patients with MI (92%) were successfully geocoded to real property data. Post-MI survival rates were 60% (50–72), 78% (71–85), 72% (60–87), and 87% (81–93) at 2 years for patients in the first (the lowest SES), second, third, and fourth quartiles of HOUSES, respectively (p < 0.001). HOUSES was associated with post-MI all-cause mortality, controlling for all variables except age and comorbidity (p = 0.036) but was not significant after adjusting for age and comorbidity (p = 0.24). Conclusions: Although HOUSES is associated with post-MI mortality, the differential mortality rates by HOUSES were primarily accounted for by age and comorbid conditions. HOUSES may be useful for health disparities research concerning cardiovascular outcomes, especially in overcoming the paucity of conventional SES measures in commonly used datasets.