Citations

Background Sex-based disparities in liver transplantation (LT) are incompletely understood. We assessed the role of height, Model for End-Stage Liver Disease (MELD), MELD-Na, and exception points in the disparate access to LT. Methods Adults waitlisted for LT at Organ Procurement and Transplantation Network between 2002 and 2013 were included. Covariates associated with likelihood of LT were analyzed by Cox proportional model. In a separate cohort of waitlisted adults with glomerular filtration rate measurement by iothalamate clearance (n = 611), we determined the number of creatinine-derived MELD points in men versus women, across all ranges of glomerular filtration rate. The impact of correcting the MELD score deficit in women on LT was modeled. Results Among 90 720 Organ Procurement and Transplantation Network registrants, women had higher mortality than men (4 years after listing: 22% vs 18%, P < 0.0001), and lower likelihood of LT (49% vs 58%, P < 0.0001); women were 20% less likely to be transplanted (hazard ratio, 0.80; 95% confidence interval, 0.78-0.81). Differences in height and MELD exception scores accounted for most of the LT deficit in women (hazard ratio, 0.91; 95% confidence interval, 0.89-0.94). Women received between 1 and 2.4 fewer creatinine-derived MELD points than men with similar renal dysfunction. MELD-Na worsened the gender disparity. Addition of 1 or 2 MELD points to women significantly impacted LT access. Conclusions Differences in height and MELD exception points explained most of the sex-based disparity in LT. Additionally, MELD score underestimated disease severity in women by up to 2.4 points and MELD Na exacerbated this disparity. The degree of underestimation based on MELD had significant impact on allocation.

AbstractBackgroundVorinostat combined with retinoids produces additive antitumor effects in preclinical studies of neuroblastoma. Higher systemic exposures of vorinostat than achieved in pediatric phase I trials with continuous daily dosing are necessary for in vivo increased histone acetylation and cytotoxic activity. We conducted a phase I trial in children with relapsed/refractory neuroblastoma to determine the maximum tolerated dose (MTD) of vorinostat on an interrupted schedule, escalating beyond the previously identified pediatric MTD.MethodsIsotretinoin (cis‐13‐retinoic acid) 80 mg/m2/dose was administered by mouth twice daily on days 1–14 in combination with escalating doses of daily vorinostat up to 430 mg/m2/dose (days 1–4; 8–11) in each 28‐day cycle using the standard 3 + 3 design. Vorinostat pharmacokinetic testing and histone acetylation assays were performed.ResultsTwenty‐nine patients with refractory or relapsed neuroblastoma were enrolled and 28 were evaluable for dose escalation decisions. Median number of cycles completed was two (range 1–15); 11 patients received four or more cycles. Three patients experienced cycle 1 dose‐limiting toxicities. A total of 18 patients experienced grade 3/4 toxicities related to study therapy. The maximum intended dose of vorinostat (430 mg/m2/day, days 1–4; 8–11) was tolerable and led to increased histone acetylation in surrogate tissues when compared to lower doses of vorinostat (P = 0.009). No objective responses were seen.ConclusionsIncreased dose vorinostat (430 mg/m2/day) on an interrupted schedule is tolerable in combination with isotretinoin. This dose led to increased vorinostat exposures and demonstrated increased histone acetylation. Prolonged stable disease in patients with minimal residual disease warrants further investigation.

BackgroundAppropriate use criteria (AUC) provide physicians guidance in test selection, and can affect health care delivery, reimbursement policy and physician decision‐making.ObjectivesThe American Society of Dermatopathology, with input from the American Academy of Dermatology and the College of American Pathologists, sought to develop AUC in dermatopathology.MethodsThe RAND/UCLA appropriateness methodology, which combines evidence‐based medicine, clinical experience and expert judgment, was used to develop AUC in dermatopathology.ResultsWith the number of ratings predetermined at 3, AUC were developed for 211 clinical scenarios involving 12 ancillary studies. Consensus was reached for 188 (89%) clinical scenarios, with 93 (44%) considered “usually appropriate,” 52 (25%) “rarely appropriate” and 43 (20%) “uncertain appropriateness.”LimitationsThe methodology requires a focus on appropriateness without comparison between tests and irrespective of cost.ConclusionsThe ultimate decision of when to order specific test rests with the physician and is one where the expected benefit exceeds the negative consequences. This publication outlines the recommendations of appropriateness—AUC for 12 tests used in dermatopathology. Importantly, these recommendations may change considering new evidence. Results deemed “uncertain appropriateness” and where consensus was not reached may benefit from further research.

Background Despite substantial evidence demonstrating clear benefit, rates of preemptive kidney transplantation (PreKTx) remain low in the United States. Our goal was to identify barriers to PreKTx. Methods Using a telephone-administered questionnaire including questions about barriers, timing of referral, timing of education, we retrospectively studied first living donor kidney transplant recipients (2006-2010) at Mayo Clinic, Rochester, MN. Of 235 patients, 145 (62%) responded to the questionnaire (74 PreKTx and 71 non-PreKTx). We compared categorical data with Fisher exact test and median times with Wilcoxon rank sum test. Results Polycystic kidney disease (PCKD), longer median time between diagnosis and transplant, and time between education about transplant and transplant correlated with PreKTx (P < 0.01). The presence of at least 1 patient-identified barrier (lack of referral, financial barriers, medical barriers, no identified living donor and donor evaluation delays) was associated with non-PreKTx (0.034) though no single barrier predominated. Age, education level, insurance status and source of referral (primary care, nephrology, and nonphysician referral) were not associated with the rate of PreKTx. Univariate logistic regression identified white race, PCKD, and increased time from diagnosis as factors favoring PreKTx; PCKD and increased time remained significant factors after multivariate analysis. Conclusions Even among a patient population that is primarily white, educated, and has a spouse or first-degree relative donor, PreKTx rates remain concerningly low. Increased time between diagnosis or education and transplant are predictors of PreKTx. Greater emphasis on transplant education earlier in the stages of chronic kidney disease and community outreach from transplant centers may help to increase the rate of PreKTx.

Objectives/HypothesisHuman papillomavirus (HPV)‐positive and HPV‐negative oropharyngeal squamous cell carcinoma (OPSCC) are distinct disease entities. Prognostic factors specific to each entity have not been adequately explored. Goals for this study were: 1) to determine whether HPV‐positive and HPV‐negative OPSCCs have distinct prognostic factors, and 2) to explore the prognostic significance of sex and race in OPSCC after HPV stratificationStudy DesignRetrospective case series.MethodsA retrospective review of 239 incident OPSCC patients from 1995 to 2012, treated at Johns Hopkins and University of California–San Francisco was conducted. Women and nonwhite races were oversampled. All analyses were stratified by tumor HPV in situ hybridization status. The effects of sex and race on survival were considered in Kaplan‐Meier and unadjusted and adjusted Cox regression models.ResultsOne hundred thirty‐four (56.1%) OPSCC patients were HPV positive. On univariate analysis, women had better overall survival than men among HPV‐positive (hazard ratio [HR]: 0.47, 95% confidence interval [CI]: 0.20‐1.07; P = .06) but not HPV‐negative (HR: 0.73, 95% CI: 0.43‐1.24; P = .24) OPSCCs. On multivariate analysis, women with HPV‐positive OPSCCs remained at lower risk of death (adjusted hazard ratio [aHR]: 0.34, 95% CI: 0.12‐0.96; P = .04). Survival did not vary significantly by race among HPV‐positive patients. Among HPV‐negative patients, Hispanic patients had significantly better survival in unadjusted (HR: 0.27, 95% CI: 0.08‐0.91; P = .04) but not adjusted (aHR: 0.93, 95% CI: 0.11‐7.36; P = .94) analysis.ConclusionsWomen with HPV‐positive OPSCC may have improved overall survival compared to men. Sex does not play a prognostic role in HPV‐negative OPSCC. There are no differences in prognosis by race among HPV‐positive or HPV‐negative patients.Level of Evidence4 Laryngoscope, E288–E296, 2018

Background: The purpose of this study was to report our long-term outcomes following reconstruction of the forearm interosseous membrane (IOM) with bone-patellar tendon-bone (BPTB) graft for treatment of chronic Essex-Lopresti injuries. Methods: We identified 33 patients who underwent IOM reconstruction with BPTB graft for chronic Essex-Lopresti injuries over a 20-year treatment interval. Twenty male and 13 female patients, with a mean age of 42.1 years (range, 19 to 73 years) and a minimum follow-up interval of 5 years, were included. Preinjury clinical examination and radiographic measurements were obtained from records for comparison with prospectively collected data. Additional functional outcome data collected postoperatively included QuickDASH (an abbreviated version of the Disabilities of the Arm, Shoulder and Hand [DASH]), modified Mayo wrist (MMW), and Broberg-Morrey elbow function scores. Results: IOM reconstruction was performed at a mean interval (and standard deviation) of 44.9 ± 60.0 months (range, 6.4 to 208 months) from the time of the initial injury. At a mean follow-up of 10.9 ± 4.4 years (range, 5.5 to 24.2 years), significant improvements were observed in mean elbow flexion-extension arc (+13° [95% confidence interval (CI), 4° to 22°]; p = 0.005), wrist flexion-extension arc (+19° [95% CI, 4° to 34°]; p = 0.016), forearm pronation-supination (+23° [95% CI, 8° to 39°]; p = 0.004), and grip strength (+25% of that of the contralateral side [95% CI, 18% to 32% of contralateral side]; p < 0.001). Improvements in ulnar variance were sustained over the long term from +3.9 mm (95% CI, 3.2 to 4.6 mm) preoperatively to −1.6 mm (95% CI, −2.3 to −0.9 mm) immediately postoperatively and −1.1 mm (95% CI, −1.8 to −0.4 mm) at the time of the final follow-up (p < 0.001). The mean QuickDASH, MMW, and Broberg-Morrey scores were 29.8 (range, 5 to 61), 82.7 (range, 60 to 100), and 91.6 (range, 64 to 100), respectively. Conclusions: IOM reconstruction with a BPTB graft is an effective treatment option for chronic Essex-Lopresti injuries, with satisfactory clinical and functional outcomes over the long term. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.