Citations

AbstractBackgroundBefore the 2014 policy change pertaining to infectious disease screening, many organ procurement organizations (OPOs) were supplementing serologic screening of deceased organ donors with nucleic acid testing (NAT) for human immunodeficiency virus (HIV‐1), hepatitis B virus (HBV), and hepatitis C virus (HCV). The number of seronegative,NAT‐positive donors has not been directly measured.MethodsHIV,HBV, andHCVscreening results of 11 229 donor referrals evaluated from 2010 to 2013 were obtained from 3OPO‐affiliated laboratories, capturing 35% of all donors in the United States. Laboratories used either polymerase chain reaction assay or transcription‐mediated amplification assay to test 9643 deceased donors byNAT.ResultsTheNATresults were positive in 21 (0.2%), 1 (0.02%), and 11 (0.1%) donors who were seronegative forHIV,HBV, andHCV, respectively. All discordantHIV‐1 results were from one laboratory using a polymrease chain reaction assay. Thirteen of the reactiveHIV NATresults in seronegative referrals were repeated and were non‐reproducibly positive (NRP). Ten (0.1%), 452 (7.8%), and 197 (2.2%) ofHIV‐,HBV‐, andHCV‐seropositive donors, respectively, were negative byNAT.ConclusionsThis study highlights the importance of robust quality assurance to minimizeNRP NATresults.NATmay allow for increased utilization of organs fromHBV‐ andHCV‐seropositive,NAT‐negative donors.

Abstract Clinical translation of intravenous therapies to treat disseminated or metastatic cancer is imperative. Comparative oncology, the evaluation of novel cancer therapies in animals with spontaneous cancer, can be utilized to inform and accelerate clinical translation. Preclinical murine studies demonstrate that single-shot systemic therapy with a vesicular stomatitis virus (VSV)-IFNβ-NIS, a novel recombinant oncolytic VSV, can induce curative remission in tumor-bearing mice. Clinical translation of VSV-IFNβ-NIS therapy is dependent on comprehensive assessment of clinical toxicities, virus shedding, pharmacokinetics, and efficacy in clinically relevant models. Dogs spontaneously develop cancer with comparable etiology, clinical progression, and response to therapy as human malignancies. A comparative oncology study was carried out to investigate feasibility and tolerability of intravenous oncolytic VSV-IFNβ-NIS therapy in pet dogs with spontaneous cancer. Nine dogs with various malignancies were treated with a single intravenous dose of VSV-IFNβ-NIS. Two dogs with high-grade peripheral T-cell lymphoma had rapid but transient remission of disseminated disease and transient hepatotoxicity that resolved spontaneously. There was no shedding of infectious virus. Correlative pharmacokinetic studies revealed elevated levels of VSV RNA in blood in dogs with measurable disease remission. This is the first evaluation of intravenous oncolytic virus therapy for spontaneous canine cancer, demonstrating that VSV-IFNβ-NIS is well-tolerated and safe in dogs with advanced or metastatic disease. This approach has informed clinical translation, including dose and target indication selection, leading to a clinical investigation of intravenous VSV-IFNβ-NIS therapy, and provided preliminary evidence of clinical efficacy and potential biomarkers that correlate with therapeutic response. Mol Cancer Ther; 17(1); 316–26. ©2017 AACR.

ObjectiveTo determine whether machine learning can accurately classify human papillomavirus (HPV) status of oropharyngeal squamous cell carcinoma (OPSCC) using computed tomography (CT)-based texture analysis.MethodsTexture analyses were retrospectively applied to regions of interest from OPSCC primary tumors on contrast-enhanced neck CT, and machine learning was used to create a model that classified HPV status with the highest accuracy. Results were compared against the blinded review of 2 neuroradiologists.ResultsThe HPV-positive (n = 92) and -negative (n = 15) cohorts were well matched clinically. Neuroradiologist classification accuracies for HPV status (44.9%, 55.1%) were not significantly different (P= 0.13), and there was a lack of agreement between the 2 neuroradiologists (κ = −0.145). The best machine learning model had an accuracy of 75.7%, which was greater than either neuroradiologist (P< 0.001,P= 0.002).ConclusionsUseful diagnostic information regarding HPV infection can be extracted from the CT appearance of OPSCC beyond what is apparent to the trained human eye.

Alignment between institutions and graduate medical education (GME) regarding quality and safety initiatives (QI) has not been measured. The objective was to determine US internal medicine residency program directors’ (IM PDs) perceived resourcing for QI and alignment between GME and their institutions. A national survey of IM PDs was conducted in the Fall of 2013. Multivariable linear regression was used to test association between a novel Integration Score (IS) measuring alignment between GME and the institution via PD perceptions. The response rate was 72.6% (265/365). According to PDs, residents were highly engaged in QI (82%), but adequate funding (14%) and support personnel (37% to 61%) were lower. Higher IS correlated to reports of funding for QI (76.3% vs 54.5%, P = .012), QI personnel (67.3% vs 41.1%, P < .001), research experts (70.5% vs 50.0%, P < .001), and computer experts (69.0% vs 45.8%, P < .001) for QI assistance. Apparent mismatch between GME and institutional resources exists, and the IS may be useful in measuring GME–institutional leadership alignment in QI.

Abstract Purpose: Glioblastoma is an aggressive and molecularly heterogeneous cancer with few effective treatment options. We hypothesized that next-generation sequencing can be used to guide treatment recommendations within a clinically acceptable time frame following surgery for patients with recurrent glioblastoma. Experimental Design: We conducted a prospective genomics-informed feasibility trial in adults with recurrent and progressive glioblastoma. Following surgical resection, genome-wide tumor/normal exome sequencing and tumor RNA sequencing were performed to identify molecular targets for potential matched therapy. A multidisciplinary molecular tumor board issued treatment recommendations based on the genomic results, blood–brain barrier penetration of the indicated therapies, drug–drug interactions, and drug safety profiles. Feasibility of generating genomics-informed treatment recommendations within 35 days of surgery was assessed. Results: Of the 20 patients enrolled in the study, 16 patients had sufficient tumor tissue for analysis. Exome sequencing was completed for all patients, and RNA sequencing was completed for 14 patients. Treatment recommendations were provided within the study's feasibility time frame for 15 of 16 (94%) patients. Seven patients received treatment based on the tumor board recommendations. Two patients reached 12-month progression-free survival, both adhering to treatments based on the molecular profiling results. One patient remained on treatment and progression free 21 months after surgery, 3 times longer than the patient's previous time to progression. Analysis of matched nonenhancing tissue from 12 patients revealed overlapping as well as novel putatively actionable genomic alterations. Conclusions: Use of genome-wide molecular profiling is feasible and can be informative for guiding real-time, central nervous system–penetrant, genomics-informed treatment recommendations for patients with recurrent glioblastoma. Clin Cancer Res; 24(2); 295–305. ©2017 AACR. See related commentary by Wick and Kessler, p. 256

We surveyed multiple apheresis centers represented by the authors for their clinical approach to the management of anticoagulation issues during therapeutic plasma exchange (TPE). We present the results of their practices and a review of the pertinent literature. As plasma is removed during TPE, replacement with all or partial non‐plasma‐containing fluids (eg, 5% albumin) may lead to significant changes in hemostasis. These changes are amplified in patients who are receiving anticoagulation. We discuss various anticoagulants as well as the monitoring and adjustment of anticoagulation before, during, and after TPE. No single guideline can be applied, but rather, patients must be monitored individually, taking into account their often complex clinical conditions and medication profiles.

The burden and predictors of hospitalization over time in community-based patients with peripheral artery disease (PAD) have not been established. This study evaluates the frequency, reasons and predictors of hospitalization over time in community-based patients with PAD. We assembled an inception cohort of 1798 PAD cases from Olmsted County, MN, USA (mean age 71.2 years, 44% female) from 1 January 1998 through 31 December 2011 who were followed until 2014. Two age- and sex-matched controls ( n = 3596) were identified for each case. ICD-9 codes were used to ascertain the primary reasons for hospitalization. Patients were censored at death or last follow-up. The most frequent reasons for hospitalization were non-cardiovascular: 68% of 8706 hospitalizations in cases and 78% of 8005 hospitalizations in controls. A total of 1533 (85%) cases and 2286 (64%) controls ( p < 0.001) were hospitalized at least once; 1262 (70%) cases and 1588 (44%) controls ( p < 0.001) ≥ two times. In adjusted models, age, prior hospitalization and comorbid conditions were independently associated with increased risk of recurrent hospitalizations in both groups. In cases, severe PAD (ankle–brachial index < 0.5) (HR: 1.25; 95% CI: 1.15, 1.36) and poorly compressible arteries (HR: 1.26; 95% CI: 1.16, 1.38) were each associated with increased risk for recurrent hospitalization. We demonstrate an increased rate of hospitalization in community-based patients with PAD and identify predictors of recurrent hospitalizations. These observations may inform strategies to reduce the burden of hospitalization of PAD patients.

BACKGROUND: Pulmonary rehabilitation (PR) is an effective intervention for COPD. However, traditional center-based PR programs suffer from low uptake. Home-based PR is a viable solution, but few studies have shown the effectiveness of remote PR, as there is a scarcity of systems that can be easily adopted in clinical practice. The aim of this report is to communicate the development and feasibility of a home PR program that includes commercially available technology that allows the PR health coach to follow the patient through his or her PR process and to present the design of a prospective clinical trial. METHODS: We developed a home PR system that includes a computer tablet, an activity monitor, and an oximeter connected to a cloud server. The home PR consists of 12 min of walking and 6 full-body exercises, to be completed 6 d/week, plus weekly telephone calls with the PR health coach. Two pilot studies were conducted in subjects with moderate-to-severe COPD. The first aimed to fine-tune the system development ( N = 3), and the second tested the program feasibility of the 8-week program ( N = 12). RESULTS: In pilot study 1, PR monitoring data from the subjects' home PR sessions were transmitted to the health coach application successfully. On a 10-point scale, participants rated the system as helpful (median = 8, interquartile range 8–9) and simple to use (median = 10, interquartile range 9–10). In pilot study 2, adherence ± SD for prescribed use was 87 ± 0.24%. Overall, participants gave the home PR system a rating of 6.2 ± 0.94 on a 7-point scale. CONCLUSIONS: A home PR program was developed that integrated health coaching and a home PR system that facilitated remote monitoring. Pilot testing indicated that the program is well-developed and feasible in a population of individuals with COPD. (ClinicalTrials.gov registration NCT02999685.)