Citations

Objectives. Increasing number of mechanical circulatory assist devices (MCADs) are being placed in heart failure patients. Morbidity from device placement is high and the outcome of patients who require noncardiac surgery after, is unclear. As laparoscopic interventions are associated with decreased morbidity, we examined the impact of such procedures in these patients. Methods. A retrospective review was conducted on 302 patients who underwent MCAD placement from 2005 to 2012. All laparoscopic abdominal surgeries were included and impact on postoperative morbidity and mortality studied. Results. Ten out of 16 procedures were laparoscopic with 1 conversion to open. Seven patients had a HeartMate II, 2 had Total Artificial Hearts, and 1 had CentriMag. Four patients had devices for ischemic cardiomyopathy and 6 cases were emergent. Surgeries included 6 laparoscopic cholecystectomies, 2 exploratory laparoscopies, 1 laparoscopic colostomy takedown, and 1 laparoscopic ventral hernia repair with mesh. Median age of the patients was 63 years (range, 29-79 years). Median operative time was 123 minutes (range, 30-380 minutes). Five of 10 patients were on preoperative anticoagulation with average intraoperative blood loss of 150 mL (range, 20-700 mL). There were 3 postoperative complications; acute respiratory failure, acute kidney injury and multisystem organ failure resulting in death not related to the surgical procedure. Conclusion. The need for noncardiac surgery in post-MCAD patients is increasing due to limited donors and due to more durable and longer support from newer generation assist devices. While surgery should be approached with caution in this high-risk group, laparoscopic surgery appears to be a safe and successful treatment option.

Purpose CALGB 49907 showed the superiority of standard therapy, which included either cyclophosphamide/doxorubicin (AC) or cyclophosphamide/methotrexate/fluorouracil over single-agent capecitabine in the treatment of patients age ≥ 65 with early-stage breast cancer. The treatment allowed dosing adjustments of methotrexate and capecitabine for pretreatment renal function. The purpose of the current analysis was to assess the relationship between pretreatment renal function and five end points: toxicity, dose modification, therapy completion, relapse-free survival, and overall survival. Methods Pretreatment renal function was defined as creatinine clearance (CrCl) using the Cockcroft-Gault equation. Multivariable logistic and proportional hazards regression were used to model separately for each regimen the relationship between CrCl and the first three binary end points and the last two time-to-event end points, respectively, after adjusting for variables of prognostic importance. Results Six hundred nineteen assessable patients were analyzed. The incidence of stage III (moderate) or stage IV (severe) renal dysfunction was 72%, 64%, and 75% for treatment with cyclophosphamide/methotrexate/fluorouracil, AC, and capecitabine, respectively. There was no relationship for any regimen between pretreatment renal function and the five end points. For AC, as CrCl increased, the odds of nonhematologic toxicity decreased (P = .008), whereas for capecitabine, as CrCl increased, the odds of experiencing toxicity of any type also increased (P = .035). Patients with renal insufficiency who received dose modifications were not at increased risk for complications compared with those who did not have renal insufficiency and received a full dose. Conclusion Excluding from clinical trials patients with renal insufficiency but good performance status on the basis of concern of excessive hematologic toxicity or poor outcomes may not be justified with appropriate dosing modifications. Results should be considered in the design of clinical trials for older patients.

Abstract The treatment of patients with metastatic non–small cell lung cancer (NSCLC) is slowly evolving from empirical cytotoxic chemotherapy to personalized treatment based on specific molecular alterations. Despite this 10-year evolution, targeted therapies have not been studied adequately in patients with resected NSCLC who have clearly defined actionable mutations. The advent of next-generation sequencing has now made it possible to characterize genomic alterations in unprecedented detail. The efforts begun by The Cancer Genome Atlas project to understand the complexities of the genomic landscape of lung cancer will be supplemented further by studying a large number of tumor specimens. The Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST) is an NCI-sponsored national clinical trials network (NCTN) initiative to address the needs to refine therapy for early-stage NSCLC. This program will screen several thousand patients with operable lung adenocarcinoma to determine whether their tumors contain specific molecular alterations [epidermal growth factor receptor mutation (EGFR) and anaplastic lymphoma kinase rearrangement (ALK)], making them eligible for treatment trials that target these alterations. Patients with EGFR mutation or ALK gene rearrangement in their tumor will be randomized to placebo versus erlotinib or crizotinib, respectively, after completion of their standard adjuvant therapy. ALCHEMIST will also contain a large discovery component that will provide an opportunity to incorporate genomic studies to fully understand the clonal architecture, clonal evolution, and mechanisms of resistance to therapy. In this review, we describe the concept, rationale, and outline of ALCHEMIST and the plan for genomic studies in patients with lung adenocarcinoma. Clin Cancer Res; 21(24); 5439–44. ©2015 AACR.

Abstract Objective The objective of the Strategic Health IT Advanced Research Project area four (SHARPn) was to develop open-source tools that could be used for the normalization of electronic health record (EHR) data for secondary use—specifically, for high throughput phenotyping. We describe the role of Intermountain Healthcare’s Clinical Element Models ([CEMs] Intermountain Healthcare Health Services, Inc, Salt Lake City, Utah) as normalization “targets” within the project. Materials and Methods Intermountain’s CEMs were either repurposed or created for the SHARPn project. A CEM describes “valid” structure and semantics for a particular kind of clinical data. CEMs are expressed in a computable syntax that can be compiled into implementation artifacts. The modeling team and SHARPn colleagues agilely gathered requirements and developed and refined models. Results Twenty-eight “statement” models (analogous to “classes”) and numerous “component” CEMs and their associated terminology were repurposed or developed to satisfy SHARPn high throughput phenotyping requirements. Model (structural) mappings and terminology (semantic) mappings were also created. Source data instances were normalized to CEM-conformant data and stored in CEM instance databases. A model browser and request site were built to facilitate the development. Discussion The modeling efforts demonstrated the need to address context differences and granularity choices and highlighted the inevitability of iso-semantic models. The need for content expertise and “intelligent” content tooling was also underscored. We discuss scalability and sustainability expectations for a CEM-based approach and describe the place of CEMs relative to other current efforts. Conclusions The SHARPn effort demonstrated the normalization and secondary use of EHR data. CEMs proved capable of capturing data originating from a variety of sources within the normalization pipeline and serving as suitable normalization targets.

Background— Severe primary (degenerative) mitral regurgitation (MR) is repaired with durable results when simple single-scallop disease is addressed. The midterm quality outcomes of minimally invasive repair for complex disease are unknown, however. Methods and Results— From January 2008 to January 2015, 487 patients (56±11 years, 360 men, ejection fraction 65±6%, 98.8% complete follow-up) underwent robotic mitral valve repair for severe nonischemic degenerative MR. Simple pathology was addressed in 289 of 487 (59%) patients, and complex repair (all others) was performed in 198 of 487 (41%). Four patients died during follow-up with a 5-year survival rate 99.5% (99.4% simple; 99.5% complex; hazard ratio, 0.48; 95% confidence interval, 0.05–4.59); and New York Heart Association functional class I/II was documented in 97.9% (477/487). Eight patients had recurrence of moderate-to-severe MR (4 simple, 4 complex), with a 5-year freedom from MR of 94.6% (96.2% simple; 92.7%, complex; P =0.67; hazard ratio, 1.36; 95% confidence interval, 0.34–5.43). Seven patients (2 simple, 5 complex), underwent mitral reoperation, with a 5-year freedom from reoperation of 97.7% (99.1% simple; 95.7% complex; P =0.13; hazard ratio, 3.35; 95% confidence interval, 0.65–17.32). Conclusions— At a large tertiary care referral center, midterm quality outcomes after robotic correction of degenerative MR are excellent, with very high survival, infrequent complications, and a low likelihood of MR recurrence, regardless of mitral valve repair complexity. Awareness of these improvements in outcome is important to inform contemporary decisions regarding high-quality alternatives to conventional and percutaneous mitral repair.

Background and Purpose— The ABC/2 score estimates intracerebral hemorrhage (ICH) volume, yet validations have been limited by small samples and inappropriate outcome measures. We determined accuracy of the ABC/2 score calculated at a specialized reading center (RC-ABC) or local site (site-ABC) versus the reference-standard computed tomography–based planimetry (CTP). Methods— In Minimally Invasive Surgery Plus Recombinant Tissue-Type Plasminogen Activator for Intracerebral Hemorrhage Evacuation-II (MISTIE-II), Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage (CLEAR-IVH) and CLEAR-III trials. ICH volume was prospectively calculated by CTP, RC-ABC, and site-ABC. Agreement between CTP and ABC/2 was defined as an absolute difference up to 5 mL and relative difference within 20%. Determinants of ABC/2 accuracy were assessed by logistic regression. Results— In 4369 scans from 507 patients, CTP was more strongly correlated with RC-ABC ( r 2 =0.93) than with site-ABC ( r 2 =0.87). Although RC-ABC overestimated CTP-based volume on average (RC-ABC, 15.2 cm 3 ; CTP, 12.7 cm3), agreement was reasonable when categorized into mild, moderate, and severe ICH (κ=0.75; P <0.001). This was consistent with overestimation of ICH volume in 6 of 8 previous studies. Agreement with CTP was greater for RC-ABC (84% within 5 mL; 48% of scans within 20%) than for site-ABC (81% within 5 mL; 41% within 20%). RC-ABC had moderate accuracy for detecting ≥5 mL change in CTP volume between consecutive scans (sensitivity, 0.76; specificity, 0.86) and was more accurate with smaller ICH, thalamic hemorrhage, and homogeneous clots. Conclusions— ABC/2 scores at local or central sites are sufficiently accurate to categorize ICH volume and assess eligibility for the CLEAR-III and MISTIE III studies and moderately accurate for change in ICH volume. However, accuracy decreases with large, irregular, or lobar clots. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: MISTIE-II NCT00224770; CLEAR-III NCT00784134.

Abstract Congenital heart diseases (CHDs) requiring surgical palliation mandate new treatment strategies to optimize long-term outcomes. Despite the mounting evidence of cardiac regeneration, there are no long-term safety studies of autologous cell-based transplantation in the pediatric setting. We aimed to establish a porcine pipeline to evaluate the feasibility and long-term safety of autologous umbilical cord blood mononuclear cells (UCB-MNCs) transplanted into the right ventricle (RV) of juvenile porcine hearts. Piglets were born by caesarean section to enable UCB collection. Upon meeting release criteria, 12 animals were randomized in a double-blinded fashion prior to surgical delivery of test article (n = 6) or placebo (n = 6). The UCB-MNC (3 × 106 cells per kilogram) or control (dimethyl sulfoxide, 10%) products were injected intramyocardially into the RV under direct visualization. The cohorts were monitored for 3 months after product delivery with assessments of cardiac performance, rhythm, and serial cardiac biochemical markers, followed by terminal necropsy. No mortalities were associated with intramyocardial delivery of UCB-MNCs or placebo. Two animals from the placebo group developed local skin infection after surgery that responded to antibiotic treatment. Electrophysiological assessments revealed no arrhythmias in either group throughout the 3-month study. Two animals in the cell-therapy group had transient, subclinical dysrhythmia in the perioperative period, likely because of an exaggerated response to anesthesia. Overall, this study demonstrated that autologous UCB-MNCs can be safely collected and surgically delivered in a pediatric setting. The safety profile establishes the foundation for cell-based therapy directed at the RV of juvenile hearts and aims to accelerate cell-based therapies toward clinical trials for CHD.