Self-Reported Everyday Functioning After COVID-19 Infection.

Importance: Changes in everyday functioning are crucial to assessing the long-term impact of COVID-19 infection. Objective: To examine the impact of COVID-19 infection on everyday functioning 18 months after infection among veterans with and without histories of COVID-19 infection. Design, Setting, and Participants: This cohort study used data from the US Veterans Affairs (VA) and included 186 veterans who had COVID-19 between October 2020 and April 2021 (ie, COVID-19 cohort) and 186 matched comparators who did not have documented COVID-19 infections (ie, control cohort). This match balanced the risk of COVID-19 based on 39 variables measured in the 24 months before infection or match, using principles of target trial emulation. Data were analyzed from December 2022 to December 2023. Exposure: First documented COVID-19. Main Outcome and Measures: The differences in self-reported everyday functioning 18 months after COVID-19 infection were estimated and compared with their matched comparators. Within-matched pair logistic and linear regressions assessed differences in outcomes and were weighted to account for sampling and nonresponse. Results: Among the 186 matched pairs of participants, their weighted mean age was 60.4 (95% CI, 57.5 to 63.2) years among veterans in the COVID-19 cohort (weighted sample, 91 459 of 101 133 [90.4%] male; 30 611 [30.3%] Black or African American veterans; 65 196 [64.4%] White veterans) and 61.1 (95% CI, 57.8 to 64.4) years among their comparators in the control cohort (91 459 [90.4%] male; 24 576 [24.3%] Black or African American veterans; 70 157 [69.4%] White veterans). A high proportion of veterans in the COVID-19 cohort (weighted percentage, 44.9% [95% CI, 34.2% to 56.2%]) reported that they could do less than what they felt they could do at the beginning of 2020 compared with the control cohort (weighted percentage, 35.3%; [95% CI, 25.6% to 46.4%]; within-matched pair adjusted odds ratio [OR], 1.52 [95% CI, 0.79 to 2.91]). There was no association of documented COVID-19 infection with fatigue, substantial pain, limitations in either activities of daily living and instrumental activities of daily living, severely curtailed life-space mobility, employment, or mean health-related quality of life on a utility scale. Conclusions and Relevance: In this cohort study of veterans with and without documented COVID-19, many reported a substantial loss of everyday functioning during the pandemic regardless of whether or not they had a documented infection with COVID-19. Future work with larger samples is needed to validate the estimated associations.

DYNATE: Localizing rare-variant association regions via multiple testing embedded in an aggregation tree.

Rare-variants (RVs) genetic association studies enable researchers to uncover the variation in phenotypic traits left unexplained by common variation. Traditional single-variant analysis lacks power; thus, researchers have developed various methods to aggregate the effects of RVs across genomic regions to study their collective impact. Some existing methods utilize a static delineation of genomic regions, often resulting in suboptimal effect aggregation, as neutral subregions within the test region will result in an attenuation of signal. Other methods use varying windows to search for signals but often result in long regions containing many neutral RVs. To pinpoint short genomic regions enriched for disease-associated RVs, we developed a novel method, DYNamic Aggregation TEsting (DYNATE). DYNATE dynamically and hierarchically aggregates smaller genomic regions into larger ones and performs multiple testing for disease associations with a controlled weighted false discovery rate. DYNATE's main advantage lies in its strong ability to identify short genomic regions highly enriched for disease-associated RVs. Extensive numerical simulations demonstrate the superior performance of DYNATE under various scenarios compared with existing methods. We applied DYNATE to an amyotrophic lateral sclerosis study and identified a new gene, EPG5, harboring possibly pathogenic mutations.

Group physical therapy for knee osteoarthritis: protocol for a hybrid type III effectiveness-implementation trial.

BACKGROUND: Knee osteoarthritis (OA) is a leading cause of chronic pain and disability and one of the most common conditions treated in outpatient physical therapy (PT). Because of the high and growing prevalence of knee OA, there is a need for efficient approaches for delivering exercise-based PT to patients with knee OA. A prior randomized controlled trial (RCT) showed that a 6-session Group Physical Therapy Program for Knee OA (Group PT) yields equivalent or greater improvements in pain and functional outcomes compared with traditional individual PT, while requiring fewer clinician hours per patient to deliver. This manuscript describes the protocol for a hybrid type III effectiveness-implementation trial comparing two implementation packages to support delivery of Group PT. METHODS: In this 12-month embedded trial, a minimum of 16 Veterans Affairs Medical Centers (VAMCs) will be randomized to receive one of two implementation support packages for their Group PT programs: a standard, low-touch support based on Replicating Effective Programs (REP) versus enhanced REP (enREP), which adds tailored, high-touch support if sites do not meet Group PT adoption and sustainment benchmarks at 6 and 9 months following launch. Implementation outcomes, including penetration (primary), adoption, and fidelity, will be assessed at 6 and 12 months (primary assessment time point). Additional analyses will include patient-level effectiveness outcomes (pain, function, satisfaction) and staffing and labor costs. A robust qualitative evaluation of site implementation context and experience, as well as site-led adaptations to the Group PT program, will be conducted. DISCUSSION: To our knowledge, this study is the first to evaluate the impact of tailored, high-touch implementation support on implementation outcomes when compared to standardized, low-touch support for delivering a PT-based intervention. The Group PT program has strong potential to become a standard offering for PT, improving function and pain-related outcomes for patients with knee OA. Results will provide information regarding the effectiveness and value of this implementation approach and a deeper understanding of how healthcare systems can support wide-scale adoption of Group PT. TRIAL REGISTRATION: This study was registered on March 7, 2022 at ClinicalTrials.gov (identifier NCT05282927 ).

A telehealth-delivered intervention to extend the veteran HIV treatment cascade for cardiovascular disease prevention: V-EXTRA-CVD study protocol for a randomized controlled trial.

Background: Veterans living with HIV have up to twice the risk of atherosclerotic cardiovascular disease (ASCVD) compared to those without HIV.Objective: Our study seeks to test a non-physician led virtual self-management implementation strategy to reduce ASCVD risk among people living with HIV (PWH). We aim to conduct a randomized control trial among PWH (n = 300) with a diagnosis of hypertension (HTN) who are enrolled in Veterans Health Administration (VHA) clinics, on suppressive antiretroviral therapy (ART), randomized 1:1 to intervention vs. education control for a 12-month duration.Methods: Using human centered design approach, we have adapted a previous 5-component telehealth focused, non-physician led intervention to a Veteran population. The education control arm receives enhanced education in addition to usual care. The primary outcome is 6 mmHg reduction in systolic BP over 12-month in the intervention arm compared to the control arm. The secondary outcome is a 12-month difference in non-HDL cholesterol. While each component of our intervention has an evidence base, they have not been tested together in an HIV context.Conclusion: The proposed multicomponent intervention has the potential to improve cardiovascular outcomes in PWH using novel virtual care methods in a patient centered care approach.

Late Mortality After COVID-19 Infection Among US Veterans vs Risk-Matched Comparators: A 2-Year Cohort Analysis.

Importance: Despite growing evidence of persistent problems after acute COVID-19, how long the excess mortality risk associated with COVID-19 persists is unknown. Objective: To measure the time course of differential mortality among Veterans who had a first-documented COVID-19 infection by separately assessing acute mortality from later mortality among matched groups with infected and uninfected individuals who survived and were uncensored at the start of each period. Design, Settings, and Participants: This retrospective cohort study used prospectively collected health record data from Veterans Affairs hospitals across the US on Veterans who had COVID-19 between March 2020 and April 2021. Each individual was matched with up to 5 comparators who had not been infected with COVID-19 at the time of matching. This match balanced, on a month-by-month basis, the risk of developing COVID-19 using 37 variables measured in the 24 months before the date of the infection or match. A primary analysis censored comparators when they developed COVID-19 with inverse probability of censoring weighting in Cox regression. A secondary analysis did not censor. Data analyses were performed from April 2021 through June 2023. Exposure: First-documented case of COVID-19 (SARS-CoV-2) infection. Main Outcome Measures: Hazard ratios for all-cause mortality at clinically meaningful intervals after infection: 0 to 90, 91 to 180, 181 to 365, and 366 to 730 days. Results: The study sample comprised 208 061 Veterans with first-documented COVID-19 infection (mean [SD] age, 60.5 (16.2) years; 21 936 (10.5) women; 47 645 [22.9] Black and 139 604 [67.1] White individuals) and 1 037 423 matched uninfected comparators with similar characteristics. Veterans with COVID-19 had an unadjusted mortality rate of 8.7% during the 2-year period after the initial infection compared with 4.1% among uninfected comparators, with censoring if the comparator later developed COVID-19-an adjusted hazard ratio (aHR) of 2.01 (95% CI, 1.98-2.04). The risk of excess death varied, being highest during days 0 to 90 after infection (aHR, 6.36; 95% CI, 6.20-6.51) and still elevated during days 91 to 180 (aHR, 1.18; 95% CI, 1.12-1.23). Those who survived COVID-19 had decreased mortality on days 181 to 365 (aHR, 0.92; 95% CI, 0.89-0.95) and 366 to 730 (aHR, 0.89; 95% CI, 0.85-0.92). These patterns were consistent across sensitivity analyses. Conclusion and Relevance: The findings of this retrospective cohort study indicate that although overall 2-year mortality risk was worse among those infected with COVID-19, by day 180 after infection they had no excess mortality during the next 1.5 years.

Design and analysis of outcomes following SARS-CoV-2 infection in veterans.

BACKGROUND: Understanding how SARS-CoV-2 infection impacts long-term patient outcomes requires identification of comparable persons with and without infection. We report the design and implementation of a matching strategy employed by the Department of Veterans Affairs' (VA) COVID-19 Observational Research Collaboratory (CORC) to develop comparable cohorts of SARS-CoV-2 infected and uninfected persons for the purpose of inferring potential causative long-term adverse effects of SARS-CoV-2 infection in the Veteran population. METHODS: In a retrospective cohort study, we identified VA health care system patients who were and were not infected with SARS-CoV-2 on a rolling monthly basis. We generated matched cohorts within each month utilizing a combination of exact and time-varying propensity score matching based on electronic health record (EHR)-derived covariates that can be confounders or risk factors across a range of outcomes. RESULTS: From an initial pool of 126,689,864 person-months of observation, we generated final matched cohorts of 208,536 Veterans infected between March 2020-April 2021 and 3,014,091 uninfected Veterans. Matched cohorts were well-balanced on all 39 covariates used in matching after excluding patients for: no VA health care utilization; implausible age, weight, or height; living outside of the 50 states or Washington, D.C.; prior SARS-CoV-2 diagnosis per Medicare claims; or lack of a suitable match. Most Veterans in the matched cohort were male (88.3%), non-Hispanic (87.1%), white (67.2%), and living in urban areas (71.5%), with a mean age of 60.6, BMI of 31.3, Gagne comorbidity score of 1.4 and a mean of 2.3 CDC high-risk conditions. The most common diagnoses were hypertension (61.4%), diabetes (34.3%), major depression (32.2%), coronary heart disease (28.5%), PTSD (25.5%), anxiety (22.5%), and chronic kidney disease (22.5%). CONCLUSION: This successful creation of matched SARS-CoV-2 infected and uninfected patient cohorts from the largest integrated health system in the United States will support cohort studies of outcomes derived from EHRs and sample selection for qualitative interviews and patient surveys. These studies will increase our understanding of the long-term outcomes of Veterans who were infected with SARS-CoV-2.

Veterans Health Administration National TeleOncology Service.

PURPOSE: As the largest integrated health care system in the United States, the Veterans Health Administration (VA) is a leader in telehealth-delivered care. All 10 million Veterans cared for within the VA are eligible for telehealth. The VA cares for approximately 46,000 Veteran patients with newly diagnosed cancer and an estimated 400,000 prevalent cases annually. With nearly 38% of VA health care system users residing in rural areas and only 44% of rural counties having an oncologist, many Veterans lack local access to specialized cancer services. METHODS: We describe the VA's National TeleOncology (NTO) Service. NTO was established to provide Veterans with the opportunity for specialized treatment regardless of geographical location. Designed as a hub-and-spoke model, VA oncologists from across the country can provide care to patients at spoke sites. Spoke sites are smaller and rural VA medical centers that are less able to independently provide the full range of services available at larger facilities. In addition to smaller rural spoke sites, NTO also provides subspecialized oncology care to Veterans located in larger VA medical facilities that do not have subspecialties available or that have limited capacity. RESULTS: As of fiscal year 2021, 23 clinics are served by or engaged in planning for delivery of NTO and there are 24 physicians providing care through the NTO virtual hub. Most NTO physicians continue to provide patient care in separate traditional in-person clinics. Approximately 4,300 unique Veterans have used NTO services. Approximately half (52%) of Veterans using NTO lived in rural areas. Most of these Veterans had more than one remote visit through NTO. CONCLUSION: NTO is a state-of-the-art model that has the potential to revolutionize the way cancer care is delivered, which should improve the experience of Veterans receiving cancer care.

BMI Trends for Veterans Up to 10 Years After VA Enrollment Following Military Discharge.

BACKGROUND: Obesity (body mass index [BMI]≥30kg/m2) among US adults has tripled over the past 45 years, but it is unclear how this population-level weight change has occurred. OBJECTIVE: We sought to identify distinct long-term BMI trajectories and examined associations with demographic and clinical characteristics. DESIGN: The design was latent trajectory modeling over 10 years of a retrospective cohort. Subgroups were identified via latent class growth mixture models, separately by sex. Weighted multinomial logistic regressions identified factors associated with subgroup membership. PARTICIPANTS: Participants were a retrospective cohort of 292,331 males and 62,898 females enrolled in VA. MAIN MEASURES: The main outcome measure was 6-month average VA-measured BMI over the course of 10 years. Additional electronic health record measures on demographic, clinical, and services utilization characteristics were also used to characterize latent trajectories. KEY RESULTS: Four trajectories were identified for men and for women, corresponding to standard BMI categories "normal weight" (BMI <25), "overweight" (BMI 25-29.99), and "with obesity" (BMI ≥30): "normal weight" and increasing (males: 28.4%; females: 22.8%), "overweight" and increasing (36.4%; 35.6%), "with obesity" and increasing (33.6%; 40.0%), and "with obesity" and stable (males: 1.6%) or decreasing (females: 1.6%). Race, ethnicity, comorbidities, mental health diagnoses, and mental health service utilization discriminated among classes. CONCLUSIONS: BMI in the 10 years following VA enrollment increased modestly. VA should continue prioritizing weight management interventions to the large number of veterans with obesity upon VA enrollment, because the majority remain with obesity.

TEAM: A MULTIPLE TESTING ALGORITHM ON THE AGGREGATION TREE FOR FLOW CYTOMETRY ANALYSIS.

In immunology studies, flow cytometry is a commonly used multivariate single-cell assay. One key goal in flow cytometry analysis is to detect the immune cells responsive to certain stimuli. Statistically, this problem can be translated into comparing two protein expression probability density functions (pdfs) before and after the stimulus; the goal is to pinpoint the regions where these two pdfs differ. Further screening of these differential regions can be performed to identify enriched sets of responsive cells. In this paper, we model identifying differential density regions as a multiple testing problem. First, we partition the sample space into small bins. In each bin, we form a hypothesis to test the existence of differential pdfs. Second, we develop a novel multiple testing method, called TEAM (Testing on the Aggregation tree Method), to identify those bins that harbor differential pdfs while controlling the false discovery rate (FDR) under the desired level. TEAM embeds the testing procedure into an aggregation tree to test from fine- to coarse-resolution. The procedure achieves the statistical goal of pinpointing density differences to the smallest possible regions. TEAM is computationally efficient, capable of analyzing large flow cytometry data sets in much shorter time compared with competing methods. We applied TEAM and competing methods on a flow cytometry data set to identify T cells responsive to the cytomegalovirus (CMV)-pp65 antigen stimulation. With additional downstream screening, TEAM successfully identified enriched sets containing monofunctional, bifunctional, and polyfunctional T cells. Competing methods either did not finish in a reasonable time frame or provided less interpretable results. Numerical simulations and theoretical justifications demonstrate that TEAM has asymptotically valid, powerful, and robust performance. Overall, TEAM is a computationally efficient and statistically powerful algorithm that can yield meaningful biological insights in flow cytometry studies.

Consensus elements for observational research on COVID-19-related long-term outcomes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its long-term outcomes may be jointly caused by a wide range of clinical, social, and economic characteristics. Studies aiming to identify mechanisms for SARS-CoV-2 morbidity and mortality must measure and account for these characteristics to arrive at unbiased, accurate conclusions. We sought to inform the design, measurement, and analysis of longitudinal studies of long-term outcomes among people infected with SARS-CoV-2. We fielded a survey to an interprofessional group of clinicians and scientists to identify factors associated with SARS-CoV-2 infection and subsequent outcomes. Using an iterative process, we refined the resulting list of factors into a consensus causal diagram relating infection and 12-month mortality. Finally, we operationalized concepts from the causal diagram into minimally sufficient adjustment sets using common medical record data elements. Total 31 investigators identified 49 potential risk factors for and 72 potential consequences of SARS-CoV-2 infection. Risk factors for infection with SARS-CoV-2 were grouped into five domains: demographics, physical health, mental health, personal social, and economic factors, and external social and economic factors. Consequences of coronavirus disease 2019 (COVID-19) were grouped into clinical consequences, social consequences, and economic consequences. Risk factors for SARS-CoV-2 infection were developed into a consensus directed acyclic graph for mortality that included two minimally sufficient adjustment sets. We present a collectively developed and iteratively refined list of data elements for observational research in SARS-CoV-2 infection and disease. By accounting for these elements, studies aimed at identifying causal pathways for long-term outcomes of SARS-CoV-2 infection can be made more informative.

Effect of Dextroamphetamine on Poststroke Motor Recovery: A Randomized Clinical Trial.

Importance: Data from animal models show that the administration of dextroamphetamine combined with task-relevant training facilitates recovery after focal brain injury. Results of clinical trials in patients with stroke have been inconsistent. Objectives: To collect data important for future studies evaluating the effect of dextroamphetamine combined with physiotherapy for improving poststroke motor recovery and to test the efficacy of the approach. Design, Setting, Participants: This pilot, double-blind, block-randomized clinical trial included patients with cortical or subcortical ischemic stroke and moderate or severe motor deficits from 5 rehabilitation hospitals or units. Participants were screened and enrolled from March 2001 through March 2003. The primary outcome was assessed 3 months after stroke. Study analysis was completed December 31, 2015. A total of 1665 potential participants were screened and 64 were randomized. Participants had to begin treatment 10 to 30 days after ischemic stroke. Data analysis was based on intention to treat. Interventions: Participants were allocated to a regimen of 10 mg of dextroamphetamine (n = 32) or placebo (n = 32) combined with a 1-hour physical therapy session beginning 1 hour after drug or placebo administration every 4 days for 6 sessions in addition to standard rehabilitation. Main Outcomes and Measures: The primary outcome was the difference between groups in change in Fugl-Meyer motor scores from baseline to 3 months after stroke (intention to treat with dextroamphetamine). Secondary exploratory measures included the National Institutes of Health Stroke Scale, Canadian Neurological Scale, Action Research Arm Test, modified Rankin Scale score, Functional Independence Measure, Ambulation Speed and Distance, Mini-Mental State Examination, Beck Depression Inventory, and Stroke Impact Scale. Results: Among the 64 patients randomized to dextroamphetamine vs placebo (55% men; median age, 66 years; age range, 27-91 years), no overall treatment-associated difference in the mean (SEM) change in Fugl-Meyer motor scores from baseline to 3 months after stroke was noted (-18.65 [2.27] points with dextroamphetamine vs -20.83 [2.94] points with placebo; P = .58). No overall treatment-associated differences in any of the study's secondary measures and no differences in subgroups based on stroke location or baseline severity were found. No adverse events were attributed to study treatments. Conclusions and Relevance: Treatment with dextroamphetamine combined with physical therapy did not improve recovery of motor function compared with placebo combined with physical therapy as assessed 3 months after hemispheric ischemic stroke. The studied treatment regimen was safe. Trial Registration: ClinicalTrials.gov identifier: NCT01905371.

A Bedside Risk Calculator to Preoperatively Distinguish Follicular Thyroid Carcinoma from Follicular Variant of Papillary Thyroid Carcinoma.

BACKGROUND: Follicular thyroid carcinoma (FTC) and follicular variant of papillary thyroid carcinoma (FV-PTC) are difficult entities to distinguish based on cytology prior to pathologic evaluation of surgical specimens but may have different treatment algorithms. The current study describes trends in rates of FTC versus FV-PTC in the U.S. and develops a risk assessment tool to aid clinicians in predicting final diagnosis and shaping treatment plans. METHODS: Relative rates of FTC and FV-PTC in the surveillance, epidemiology, and end results (SEER) database were evaluated for temporal trends from 1988 to 2011. Using multivariable logistic regression, a simplified scoring system was developed to estimate the risk of FTC versus FV-PTC using patient and tumor characteristics. The National Cancer Data Base was used for model validation. RESULTS AND DISCUSSION: Of 115,091 thyroid cancer cases in the SEER database from 1988 to 2011, 23,980 involved FTC (n = 5056; 21 %) or FV-PTC (n = 18,924; 79 %). In 1988, half of follicular cases were FV-PTC; however, FV-PTC accounted for over 85 % of these lesions by 2010. Increasing age >45 years, male gender, black race, increasing tumor size, and distant metastases were strongly associated with increased risk of FTC, while lymph node disease and extrathyroidal extension were associated with FV-PTC. A bedside risk assessment nomogram using these preoperative variables classified patient risk of FTC from 2 to 70 %. FV-PTC has become the dominant malignancy with follicular cytology, accounting for >85 % of these cases. A simple bedside risk assessment tool can risk stratify patients with follicular lesions and inform patient and clinician discussions and decision making.

Evaluation of Selvester QRS score for use in presence of conduction abnormalities in a broad population.

BACKGROUND: The Selvester QRS score is an electrocardiographic tool designed to quantify myocardial scar. It was updated in 2009 to expand its usefulness in patients with conduction abnormalities such as bundle-branch and fascicular blocks. There is need to further validate the updated score in a broader group of patients with cardiovascular disease and conduction abnormalities. We primarily hypothesized that the updated score could distinguish between presence and absence of scar by cardiac magnetic resonance imaging (CMR) with late gadolinium enhancement in 4 groups of patients with distinct conduction abnormalitites. METHODS: A total of 193 patients were retrospectively identified that had received an electrocardiogram (ECG) and a CMR scan at Duke University Medical Center between January 2011 and August 2013: 62 with left bundle-branch block, 51 with right bundle-branch block (RBBB), 43 with left anterior fascicular block (LAFB), and 37 with RBBB + LAFB. Scar sizes estimated by ECG and by CMR were compared using scatterplots, modified Bland-Altman plots, and receiver operating characteristics curves. RESULTS: Of 193 patients, 96 (50%) had no scar by CMR. The QRS score generally overestimated CMR scar. The area under the curve ranged between 0.62 and 0.65 for the different conduction types, and 95% confidence intervals included 0.5 for all conduction types. Performance was slightly improved in LAFB and RBBB + LAFB by excluding all points derived from leads V4-V6. CONCLUSIONS: The Selvester QRS score for use in conduction abnormalities needs to be improved, primarily its specificity, to enable effective clinical use in a population with a wide range of left ventricular ejection fraction and low pretest probability of myocardial scar.

Presence and Number of Lymph Node Metastases Are Associated With Compromised Survival for Patients Younger Than Age 45 Years With Papillary Thyroid Cancer.

PURPOSE: Cervical lymph node metastases are recognized as a prognostic indicator only in patients age 45 years or older with papillary thyroid cancer (PTC); patients younger than age 45 years are perceived to have low-risk disease. The current American Joint Committee on Cancer staging for PTC in patients younger than age 45 years does not include cervical lymph node metastases. Our objective was to test the hypothesis that the presence and number of cervical lymph node metastases have an adverse impact on overall survival (OS) in patients younger than age 45 years with PTC. PATIENTS AND METHODS: Adult patients younger than age 45 years undergoing surgery for stage I PTC (no distant metastases) were identified from the National Cancer Data Base (NCDB; 1998-2006) and from SEER 1988-2006 data. Multivariable models were used to examine the association of OS with the presence of lymph node metastases and number of metastatic nodes. RESULTS: In all, 47,902 patients in NCDB (11,740 with and 36,162 without nodal metastases) and 21,855 in the SEER database (5,188 with and 16,667 without nodal metastases) were included. After adjustment, OS was compromised for patients with nodal metastases compared with patients who did not have them (NCDB: hazard ratio (HR), 1.32; 95% CI, 1.04 to 1.67; P = .021; SEER: HR, 1.29; 95% CI, 1.08 to 1.56; P = .006). After adjustment, increasing number of metastatic lymph nodes was associated with decreasing OS up to six metastatic nodes (HR, 1.12; 95% CI, 1.01 to 1.25; P = .03), after which more positive nodes conferred no additional mortality risk (HR, 0.99; 95% CI, 0.99 to 1.05; P = .75). CONCLUSION: Our results suggest that cervical lymph node metastases are associated with compromised survival in young patients, warranting consideration of revised American Joint Committee on Cancer staging. A change point of six or fewer metastatic lymph nodes seems to carry prognostic significance, thus advocating for rigorous preoperative screening for nodal metastases.

Comparison of 2-Year Outcomes of Extended Criteria Cardiac Transplantation Versus Destination Left Ventricular Assist Device Therapy Using Continuous Flow.

Alternatives have emerged for patients ineligible for cardiac transplantation under standard criteria. The purpose of our study was to compare outcomes in patients ineligible for cardiac transplantation under standard criteria, treated either with extended criteria cardiac transplantation (ECCT) or a continuous flow destination therapy left ventricular assist device (CF DT-LVAD). From 2005 to 2012, patients treated with either ECCT or CF DT-LVAD at our institution were retrospectively analyzed. In the overall unmatched cohort, we examined mortality and other outcomes, including index hospitalization length of stay, renal function, stroke, and readmission rates. After propensity score (PS) matching, outcomes were compared between ECCT and CF DT-LVAD recipients. Overall, 62 patients underwent ECCT, and 146 patients were treated with CF DT-LVAD. The 2-year mortality estimate for ECCT recipients was 27.3% (95% confidence interval 15.5% to 39.1%) and for CF DT-LVAD recipients was 11.2% (95% confidence interval 4.8% to 17.6%). After PS matching of 39 patients from each treatment group, there was no significant difference in overall survival after 2 years (p = 0.346). In both unmatched and PS-matched analyses, CF DT-LVAD patients compared with ECCT had a significantly higher estimated glomerular filtration rate at 1 year but also had significantly higher hospital readmission rates. Stroke also more commonly occurred after CF DT-LVAD compared with ECCT (17 vs 5, unmatched; and 2 vs 1, PS matched). However, there was no significant difference between PS-matched groups in 2-year stroke-free survival (p = 0.371). In conclusion, ECCT and CF DT-LVAD in select patients are comparable therapies with respect to 2-year survival.

Impact of extent of surgery on survival for papillary thyroid cancer patients younger than 45 years.

CONTEXT: Papillary thyroid cancer (PTC) patients <45 years old are considered to have an excellent prognosis; however, current guidelines recommend total thyroidectomy for PTC tumors >1.0 cm, regardless of age. OBJECTIVE: Our objective was to examine the impact of extent of surgery on overall survival (OS) in patients <45 years old with stage I PTC of 1.1 to 4.0 cm. DESIGN, SETTING, AND PATIENTS: Adult patients <45 years of age undergoing surgery for stage I PTC were identified from the National Cancer Data Base (NCDB, 1998-2006) and the Surveillance, Epidemiology, and End RESULTS dataset (SEER, 1988-2006). MAIN OUTCOME MEASURE: Multivariable modeling was used to compare OS for patients undergoing total thyroidectomy vs lobectomy. RESULTS: In total, 29 522 patients in NCDB (3151 lobectomy, 26 371 total thyroidectomy) and 13 510 in SEER (1379 lobectomy, 12 131 total thyroidectomy) were included. Compared with patients undergoing lobectomy, patients having total thyroidectomy more often had extrathyroidal and lymph node disease. At 14 years, unadjusted OS was equivalent between total thyroidectomy and lobectomy in both databases. After adjustment, OS was similar for total thyroidectomy compared with lobectomy across all patients with tumors of 1.1 to 4.0 cm (NCDB: hazard ratio = 1.45 [confidence interval = 0.88-2.51], P = 0.19; SEER: 0.95 (0.70-1.29), P = 0.75) and when stratified by tumor size: 1.1 to 2.0 cm (NCDB: 1.12 [0.50-2.51], P = 0.78; SEER: 0.95 [0.56-1.62], P = 0.86) and 2.1 to 4.0 cm (NCDB: 1.93 [0.88-4.23], P = 0.10; SEER: 0.94 [0.60-1.49], P = 0.80). CONCLUSIONS: After adjusting for patient and clinical characteristics, total thyroidectomy compared with thyroid lobectomy was not associated with improved survival for patients <45 years of age with stage I PTC of 1.1 to 4.0 cm. Additional clinical and pathologic factors should be considered when choosing extent of resection.

Effects of left ventricular assist device support on biomarkers of cardiovascular stress, fibrosis, fluid homeostasis, inflammation, and renal injury.

OBJECTIVES: The purpose of this study was to examine changes in a broad panel of biomarkers following left ventricular assist device (LVAD) support in advanced heart failure (HF). BACKGROUND: LVAD therapy mechanically unloads the failing heart and may result in reversal of certain aspects of the end-stage HF phenotype. Changes in markers of myocardial stress, fibrosis, inflammation, fluid homeostasis, and renal injury in this setting are unknown. METHODS: Amino-terminal pro-B-type natriuretic peptide (NT-proBNP), galectin-3, ST2, copeptin, growth differentiation factor (GDF)-15, C-reactive protein (CRP), and neutrophil gelatinase associated lipocalin (NGAL) levels were measured in frozen plasma collected from 37 individuals prior to continuous flow LVAD implantation and a median of 136 (interquartile range: 94 to 180) days after implantation. RESULTS: The median age of patients was 68 years old. LVAD therapy was associated with significant decreases in NT-proBNP (3,093 to 2,090 pg/ml; p = 0.02), ST2 (67.5 to 45.2 ng/ml, p <0.01), galectin-3 (24.7 to 22.0 ng/ml; p = 0.04), GDF-15 (3,232 to 2,613 ng/l;p <0.001), hs-CRP (22.4 to 11.9 mg/l; p = 0.01), and copeptin (103 to 94 pmol/l; p = 0.003) but not NGAL (132 to 135 ng/ml; p = 0.06). Despite improvement over time, absolute values of each biomarker remained extremely abnormal. Greater reductions in biomarkers were noted in individuals with >25% decrease in NT-proBNP concentrations but reached statistical significance only in the case of galectin-3 (p = 0.01). CONCLUSIONS: The biomarker profile in patients after LVAD placement improves but nonetheless remains significantly abnormal. Our results suggest the need for targeted therapeutic interventions to mitigate such abnormalities and potentially increase rates of myocardial recovery.

Malignant struma ovarii: a population-level analysis of a large series of 68 patients.

BACKGROUND: Malignant struma ovarii (MSO) is a germ cell tumor of the ovary histologically identical to differentiated thyroid cancers. There is a paucity of data on this neoplasm, with fewer than 200 reported cases. The primary objective of this study was to examine the survival rate of women diagnosed with MSO using data from the Surveillance, Epidemiology, and End RESULTS (SEER) database. Secondary objectives were to describe the demographic, clinical, pathologic, and treatment characteristics of this population. METHODS: A retrospective analysis was performed of prospectively collected cancer registry data. A total of 68 patients were identified in the SEER database, 1973-2011. The chi-square test, Student's t-test, and Kaplan-Meier curves were employed for data analyses. RESULTS: All 68 patients were females with a mean age at diagnosis of 43.0 years. Nearly 33% underwent unilateral oophorectomy, 28.6% bilateral oophorectomy, and 28.6% oophorectomy and omentectomy, and 4.8% were treated with debulking surgery. Pelvic radiation was administered to 12.3% of patients. The mean tumor size was 52.8 mm; 80% of malignant struma ovarii were SEER staged as local. Overall survival rates at 5, 10, and 20 years were 96.7%, 94.3%, and 84.9% respectively. Among the patients, there were six deaths recorded; only one was attributed to MSO. Six individuals (8.8%) had a concomitant or subsequent diagnosis of thyroid cancer. Four patients underwent total thyroidectomy, three patients had radioactive iodine, and one patient underwent external beam radiation. Two thirds of thyroid cancers extended outside the thyroid gland. All six patients with thyroid cancer were alive at the end of follow-up. CONCLUSIONS: It was observed that patients with malignant struma ovarii had an excellent disease-specific survival rate, regardless of the management strategy employed. However, MSO patients had a high risk for developing aggressive thyroid cancers. Therefore, MSO patients may benefit from routine thyroid imaging once the diagnosis of MSO is established.

Extent of surgery for papillary thyroid cancer is not associated with survival: an analysis of 61,775 patients.

OBJECTIVE: To examine the association between the extent of surgery and overall survival in a large contemporary cohort of patients with papillary thyroid cancer (PTC). BACKGROUND: Guidelines recommend total thyroidectomy for PTC tumors >1 cm, based on older data demonstrating an overall survival advantage for total thyroidectomy over lobectomy. METHODS: Adult patients with PTC tumors 1.0-4.0 cm undergoing thyroidectomy in the National Cancer Database, 1998-2006, were included. Cox proportional hazards models were applied to measure the association between the extent of surgery and overall survival while adjusting for patient demographic and clinical factors, including comorbidities, extrathyroidal extension, multifocality, nodal and distant metastases, and radioactive iodine treatment. RESULTS: Among 61,775 PTC patients, 54,926 underwent total thyroidectomy and 6849 lobectomy. Compared with lobectomy, patients undergoing total thyroidectomy had more nodal (7% vs 27%), extrathyroidal (5% vs 16%), and multifocal disease (29% vs 44%) (all Ps < 0.001). Median follow-up was 82 months (range, 60-179 months). After multivariable adjustment, overall survival was similar in patients undergoing total thyroidectomy versus lobectomy for tumors 1.0-4.0 cm [hazard ratio (HR) = 0.96; 95% confidence interval (CI), 0.84-1.09); P = 0.54] and when stratified by tumor size: 1.0-2.0 cm [HR = 1.05; 95% CI, 0.88-1.26; P = 0.61] and 2.1-4.0 cm [HR = 0.89; 95% CI, 0.73-1.07; P = 0.21]. Older age, male sex, black race, lower income, tumor size, and presence of nodal or distant metastases were independently associated with compromised survival (P < 0.0001). CONCLUSIONS: Current guidelines suggest total thyroidectomy for PTC tumors >1 cm. However, we did not observe a survival advantage associated with total thyroidectomy compared with lobectomy. These findings call into question whether tumor size should be an absolute indication for total thyroidectomy.