Citations

Objectives: The purpose of this study is to investigate the ability of competitive athletes to remain at a high level of competition following osteochondral allograft transplantation (OCA) of the knee. Methods: A retrospective review was performed to identify all competitive athletes (high school, collegiate, professional) who underwent an isolated femoral condyle OCA between 2004 and 2012. Patient reported outcome (PRO) questionnaires (Lysholm, International Knee Documentation Committee (IKDC), Knee Injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMasters Universities Arthritis Index (WOMAC), Short Form-12 (SF-12), Tegner, and Marx) and custom return-to-sport surveys were administered. All subsequent reoperations were documented. Results: A total of 13 (7 male, 6 female) athletes were identified with an average follow-up of 5.9 ± 2.5 years. Four athletes competed at an intercollegiate level, while 9 played high-level high-school sports. Seven athletes returned to competitive sport (54%) at an average of 7.9 ± 3.5 months, five of whom were returned to pre-injury levels of play. Of the eight athletes who either did not return to sport or failed to sustain their high level of play, the most common reasons cited were a change in life circumstances, such as graduation, or a fear of re-injury (Figure 1). At final follow-up, regardless of return-to-play, all athletes had significant improvements in all PRO scores except for KOOS-Sport, WOMAC-Stiffness, and SF-12 Mental subscales. Tegner Activity scores dropped significantly from pre-injury to final follow-up (8.2 ± 2.4, 4.5 ± 2.1, p < 0.01). There were three reoperations and zero instances of graft failure. Conclusion: OCAs provide acceptable rates of return-to-play and excellent long-term outcomes for high-level athletes with large osteochondral defects. Social factors are three times more likely than persistent pain to prevent return to sport.

Abstract Rationale Usual interstitial pneumonia (UIP) is the histopathologic hallmark of idiopathic pulmonary fibrosis. Although UIP can be detected by high-resolution computed tomography of the chest, the results are frequently inconclusive, and pathology from transbronchial biopsy (TBB) has poor sensitivity. Surgical lung biopsy may be necessary for a definitive diagnosis. Objectives To develop a genomic classifier in tissue obtained by TBB that distinguishes UIP from non-UIP, trained against central pathology as the reference standard. Methods Exome enriched RNA sequencing was performed on 283 TBBs from 84 subjects. Machine learning was used to train an algorithm with high rule-in (specificity) performance using specimens from 53 subjects. Performance was evaluated by cross-validation and on an independent test set of specimens from 31 subjects. We explored the feasibility of a single molecular test per subject by combining multiple TBBs from upper and lower lobes. To address whether classifier accuracy depends upon adequate alveolar sampling, we tested for correlation between classifier accuracy and expression of alveolar-specific genes. Results The top-performing algorithm distinguishes UIP from non-UIP conditions in single TBB samples with an area under the receiver operator characteristic curve (AUC) of 0.86, with specificity of 86% (confidence interval = 71–95%) and sensitivity of 63% (confidence interval = 51–74%) (31 test subjects). Performance improves to an AUC of 0.92 when three to five TBB samples per subject are combined at the RNA level for testing. Although we observed a wide range of type I and II alveolar–specific gene expression in TBBs, expression of these transcripts did not correlate with classifier accuracy. Conclusions We demonstrate proof of principle that genomic analysis and machine learning improves the utility of TBB for the diagnosis of UIP, with greater sensitivity and specificity than pathology in TBB alone. Combining multiple individual subject samples results in increased test accuracy over single sample testing. This approach requires validation in an independent cohort of subjects before application in the clinic.

Abstract Background Despite advances in modern therapy, high-grade gliomas continue to portend a dismal prognosis and nearly all patients will experience relapse. Unfortunately, salvage options remain limited. In this study, we assessed outcomes for patients with recurrent gliomas treated with reirradiation. Methods We retrospectively identified 48 glioma patients treated with reirradiation between 2013 and 2016. All had radiographic or pathologic evidence of recurrence. Prognostic factors were abstracted from the electronic medical record. Results Initial surgery included biopsy in 15, subtotal resection in 21, and gross total resection in 12. Initial chemotherapy included temozolomide (TMZ) in 31, TMZ+dasatinib in 7, TMZ+vorinostat in 3, and procarbazine, lomustine, and vincristine in 2. The median dose of primary radiotherapy was 60 Gy delivered in 30 fractions. Median overall survival (OS) and progression-free survival (PFS) from initial diagnosis were 3.2 and 1.7 years, respectively. A total of 36 patients failed salvage bevacizumab before reirradiation. Salvage surgery was performed before reirradiation in 21 patients. Median time to reirradiation was 1.7 years. Median follow-up was 13.7 months from reirradiation. Concurrent systemic therapy was given in 33 patients (bevacizumab in 27, TMZ in 8, and lomustine in 2). Median PFS and OS after reirradiation were 3.2 and 6.3 months, respectively. Radionecrosis occurred in 4 patients and no radionecrosis was seen in patients receiving concurrent bevacizumab with reirradiation (0% vs 19%, P = .03). Conclusions Reirradiation may result in delayed tumor progression with acceptable toxicity. Prospective trials are needed to determine the impact of reirradiation on tumor progression and quality of life.

BackgroundProlongation of the QT on the surface electrocardiogram can be due to either genetic or acquired causes. Distinguishing congenital long QT syndrome (LQTS) from acquired QT prolongation has important prognostic and management implications. We aimed to investigate if quantitative T‐wave analysis could provide a tool for the physician to differentiate between congenital and acquired QT prolongation.MethodsPatients were identified through an institution‐wide computer‐based QT screening system which alerts the physician if the QTc ≥ 500 ms. ECGs were retrospectively analyzed with an automated T‐wave analysis program. Congenital LQTS was compared in a 1:3 ratio to those with an identified acquired etiology for QT prolongation (electrolyte abnormality and/or prescription of known QT prolongation medications). Linear discriminant analysis was performed using 10‐fold cross‐validation to statistically test the selected features.ResultsThe 12‐lead ECG of 38 patients with congenital LQTS and 114 patients with drug‐induced and/or electrolyte‐mediated QT prolongation were analyzed. In lead V5, patients with acquired QT prolongation had a shallower T wave right slope (−2,322 vs. −3,593 mV/s), greater T‐peak‐Tend interval (109 vs. 92 ms), and smaller T wave center of gravity on the x axis (290 ms vs. 310 ms; p < .001). These features could distinguish congenital from acquired causes in 77% of cases (sensitivity 90%, specificity 58%).ConclusionT‐wave morphological analysis on lead V5 of the surface ECG could successfully differentiate congenital from acquired causes of QT prolongation.