This study evaluates the prognostic performance of a 15 gene expression profiling (GEP) assay that assigns primary posterior uveal melanomas to prognostic subgroups: class 1 (low metastatic risk) and ...class 2 (high metastatic risk).
Prospective, multicenter study.
A total of 459 patients with posterior uveal melanoma were enrolled from 12 independent centers.
Tumors were classified by GEP as class 1 or class 2. The first 260 samples were also analyzed for chromosome 3 status using a single nucleotide polymorphism assay. Net reclassification improvement analysis was performed to compare the prognostic accuracy of GEP with the 7th edition clinical Tumor-Node-Metastasis (TNM) classification and chromosome 3 status.
Patients were managed for their primary tumor and monitored for metastasis.
The GEP assay successfully classified 446 of 459 cases (97.2%). The GEP was class 1 in 276 cases (61.9%) and class 2 in 170 cases (38.1%). Median follow-up was 17.4 months (mean, 18.0 months). Metastasis was detected in 3 class 1 cases (1.1%) and 44 class 2 cases (25.9%) (log-rank test, P<10(-14)). Although there was an association between GEP class 2 and monosomy 3 (Fisher exact test, P<0.0001), 54 of 260 tumors (20.8%) were discordant for GEP and chromosome 3 status, among which GEP demonstrated superior prognostic accuracy (log-rank test, P = 0.0001). By using multivariate Cox modeling, GEP class had a stronger independent association with metastasis than any other prognostic factor (P<0.0001). Chromosome 3 status did not contribute additional prognostic information that was independent of GEP (P = 0.2). At 3 years follow-up, the net reclassification improvement of GEP over TNM classification was 0.43 (P = 0.001) and 0.38 (P = 0.004) over chromosome 3 status.
The GEP assay had a high technical success rate and was the most accurate prognostic marker among all of the factors analyzed. The GEP provided a highly significant improvement in prognostic accuracy over clinical TNM classification and chromosome 3 status. Chromosome 3 status did not provide prognostic information that was independent of GEP.
We used high-resolution spectral-domain optical coherence tomography (SD-OCT) with retinal segmentation to determine how ganglion cell loss relates to history of acute optic neuritis (ON), retinal ...nerve fiber layer (RNFL) thinning, visual function, and vision-related quality of life (QOL) in multiple sclerosis (MS).
Cross-sectional study.
A convenience sample of patients with MS (n = 122; 239 eyes) and disease-free controls (n = 31; 61 eyes). Among MS eyes, 87 had a history of ON before enrollment.
The SD-OCT images were captured using Macular Cube (200×200 or 512×128) and ONH Cube 200×200 protocols. Retinal layer segmentation was performed using algorithms established for glaucoma studies. Thicknesses of the ganglion cell layer/inner plexiform layer (GCL+IPL), RNFL, outer plexiform/inner nuclear layers (OPL+INL), and outer nuclear/photoreceptor layers (ONL+PRL) were measured and compared in MS versus control eyes and MS ON versus non-ON eyes. The relation between changes in macular thickness and visual disability was also examined.
The OCT measurements of GCL+IPL and RNFL thickness; high contrast visual acuity (VA); low-contrast letter acuity (LCLA) at 2.5% and 1.25% contrast; on the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and 10-Item Neuro-Ophthalmic Supplement composite score.
Macular RNFL and GCL+IPL were significantly decreased in MS versus control eyes (P<0.001 and P = 0.001) and in MS ON versus non-ON eyes (P<0.001 for both measures). Peripapillary RNFL, macular RNFL, GCL+IPL, and the combination of macular RNFL+GCL+IPL were significantly correlated with VA (P≤0.001), 2.5% LCLA (P<0.001), and 1.25% LCLA (P≤0.001). Among OCT measurements, reductions in GCL+IPL (P<0.001), macular RNFL (P = 0.006), and the combination (macular RNFL+GCL+IPL; P<0.001) were most strongly associated with lower (worse) NEI-VFQ-25 and 10-Item Supplement QOL scores; GCL+IPL thinning was significant even accounting for macular RNFL thickness (P = 0.03 for GCL+IPL, P = 0.39 for macular RNFL).
We demonstrated that GCL+IPL thinning is most significantly correlated with both visual function and vision-specific QOL in MS, and may serve as a useful structural marker of disease. Our findings parallel those of magnetic resonance imaging studies that show gray matter disease is a marker of neurologic disability in MS.
Proprietary or commercial disclosure may be found after the references.
Abstract Objective This study examined a primary care-based program to address the health needs of women recently released from incarceration by facilitating access to primary medical, mental health, ...and substance use disorder (SUD) treatment. Study Design Peer community health workers recruited women released from incarceration within the past 9 months into the Women's Initiative Supporting Health Transitions Clinic (WISH-TC). Located within an urban academic medical center, WISH-TC uses cultural, gender, and trauma-specific strategies grounded in the self-determination theory of motivation. Data abstracted from intake forms and medical charts were examined using bivariate and multivariable regression analyses. Results Of the 200 women recruited, 100 attended the program at least once. Most (83.0%) did not have a primary care provider before enrollment. Conditions more prevalent than in the general population included psychiatric disorders (94.0%), substance use (90.0%), intimate partner violence (66.0%), chronic pain (66.0%), and hepatitis C infection (12.0%). Patients received screening and vaccinations (65.9%–87.0%), mental health treatment (91.5%), and SUD treatment (64.0%). Logistic regression revealed that receipt of mental health treatment was associated with number of psychiatric (adjusted odds ratio AOR, = 4.09; p < .01), and social/behavioral problems (AOR, 2.67; p = .04), and higher median income (AOR, 1.07; p = .05); African American race predicted lower receipt of SUD treatment (AOR, 0.08; p < .01). Conclusions An innovative primary care transitions program successfully helped women recently released from incarceration to receive medical, mental health, and SUD treatment. Primary care settings with specialty programs, including community health workers, may provide a venue to screen, assess, and help recently incarcerated women access needed care.
Objectives Anatomic segmentectomy is increasingly being considered as a means of achieving an R0 resection for peripheral, small, stage I non–small-cell lung cancer. In the current study, we compare ...the results of video-assisted thoracic surgery (n = 104) versus open (n = 121) segmentectomy in the treatment of stage I non–small-cell lung cancer. Methods A total of 225 consecutive anatomic segmentectomies were performed for stage IA (n = 138) or IB (n = 87) non–small-cell lung cancer from 2002 to 2007. Primary outcome variables included hospital course, complications, mortality, recurrence, and survival. Statistical comparisons were performed utilizing the t test and Fisher exact test. The probability of overall and recurrence-free survival was estimated with the Kaplan-Meier method, with significance being estimated by the log-rank test. Results Mean age (69.9 years) and gender distribution were similar between the video-assisted thoracic surgery and open groups. Average tumor size was 2.3 cm (2.1 cm video-assisted thoracic surgery; 2.4 cm open). Mean follow-up was 16.2 (video-assisted thoracic surgery) and 28.2 (open) months. There were 2 perioperative deaths (2/225; 0.9%), both in the open group. Video-assisted thoracic surgery segmentectomy was associated with decreased length of stay (5 vs 7 days, P < .001) and pulmonary complications (15.4% vs 29.8%, P = .012) compared with open segmentectomy. Overall mortality, complications, local and systemic recurrence, and survival were similar between video-assisted thoracic surgery and open segmentectomy groups. Conclusions Video-assisted thoracic surgery segmentectomy can be performed with acceptable morbidity, mortality, recurrence, and survival. The video-assisted thoracic surgery approach affords a shorter length of stay and fewer postoperative pulmonary complications compared with open techniques. The potential benefits and limitations of segmentectomy will need to be further evaluated by prospective, randomized trials.
Summary Background Most patients with multiple sclerosis without previous optic neuritis have thinner retinal layers than healthy controls. We assessed the role of peripapillary retinal nerve fibre ...layer (pRNFL) thickness and macular volume in eyes with no history of optic neuritis as a biomarker of disability worsening in a cohort of patients with multiple sclerosis who had at least one eye without optic neuritis available. Methods In this multicentre, cohort study, we collected data about patients (age ≥16 years old) with clinically isolated syndrome, relapsing-remitting multiple sclerosis, and progressive multiple sclerosis. Patients were recruited from centres in Spain, Italy, France, Germany, Czech Republic, Netherlands, Canada, and the USA, with the first cohort starting in 2008 and the latest cohort starting in 2013. We assessed disability worsening using the Expanded Disability Status Scale (EDSS). The pRNFL thickness and macular volume were assessed once at study entry (baseline) by optical coherence tomography (OCT) and was calculated as the mean value of both eyes without optic neuritis for patients without a history of optic neuritis or the value of the non-optic neuritis eye for patients with previous unilateral optic neuritis. Researchers who did the OCT at baseline were masked to EDSS results and the researchers assessing disability with EDSS were masked to OCT results. We estimated the association of pRNFL thickness or macular volume at baseline in eyes without optic neuritis with the risk of subsequent disability worsening by use of proportional hazards models that included OCT metrics and age, disease duration, disability, presence of previous unilateral optic neuritis, and use of disease-modifying therapies as covariates. Findings 879 patients with clinically isolated syndrome (n=74), relapsing-remitting multiple sclerosis (n=664), or progressive multiple sclerosis (n=141) were included in the primary analyses. Disability worsening occurred in 252 (29%) of 879 patients with multiple sclerosis after a median follow-up of 2·0 years (range 0·5–5 years). Patients with a pRNFL of less than or equal to 87 μm or less than or equal to 88 μm (measured with Spectralis or Cirrus OCT devices) had double the risk of disability worsening at any time after the first and up to the third years of follow-up (hazard ratio 2·06, 95% CI 1·36–3·11; p=0·001), and the risk was increased by nearly four times after the third and up to the fifth years of follow-up (3·81, 1·63–8·91; p=0·002). We did not identify meaningful associations for macular volume. Interpretation Our results provide evidence of the usefulness of monitoring pRNFL thickness by OCT for prediction of the risk of disability worsening with time in patients with multiple sclerosis. Funding Instituto de Salud Carlos III.
In the current study, we analyze the impact of pathologic variables (angiolymphatic invasion, visceral pleural invasion, and tumor inflammation) upon survival outcomes after segmentectomy or ...lobectomy for stage I non-small cell lung cancer.
A retrospective review was made of 524 patients undergoing resection of stage I non-small cell lung cancer through either lobectomy (n = 285) or anatomic segmentectomy (n = 239). Primary outcome variables include recurrence-free and overall survival. Statistical comparisons were performed with the t test and Fisher's exact test. Recurrence-free and overall survival was estimated utilizing the Kaplan-Maier method, with statistical significance being assessed by the log rank test.
The incidence of angiolymphatic invasion, visceral pleural invasion, and degree of tumor inflammation, as well as morbidity, mortality, and length of stay were similar between segmentectomy and lobectomy. The presence of angiolymphatic invasion or visceral pleural invasion was associated with a significant decrease in recurrence-free survival (p < 0.01) and overall survival (p < 0.01). There was a trend for decreased recurrence with increasing tumor inflammation (mild versus severe, p = 0.066). There was no difference in rates of local recurrence (5.6% versus 7.9%, p = 0.59) or survival (p = 0.455) between segmentectomy and lobectomy, respectively.
Angiolymphatic and visceral pleural invasion appear to be strong adverse prognostic factors after anatomic resection by segmentectomy or lobectomy for stage I non-small cell lung cancer. Overall survival is not affected by the extent of anatomical surgical resection. These data may have implications regarding the role of adjuvant systemic therapy after surgical resection for tumors with these pathologic characteristics.
Objectives The aim of this study was to investigate the use of durable mechanical circulatory support (MCS) in patients with chemotherapy-induced cardiomyopathy (CCMP) and determine their outcomes ...and survival in comparison to that of other patients with end-stage heart failure treated similarly. Background Patients with end-stage heart failure as a result of CCMP from anthracyclines are often precluded from heart transplantation because of a history of cancer. In such patients, durable MCS may offer an important chance for life prolongation. Yet, there are no data to support the use of MCS in this increasingly prevalent group of patients. Methods We searched 3,812 MCS patients from June 2006 through March 2011 in the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) database for the diagnosis of CCMP. We compared characteristics, outcomes, and survival between CCMP patients and patients with nonischemic cardiomyopathy and ischemic cardiomyopathy. Results Compared with patients with nonischemic cardiomyopathy and ischemic cardiomyopathy, patients with CCMP were overwhelmingly female (72% vs. 24% vs. 13%, p = 0.001), had MCS more often implanted as destination therapy (33% vs. 14% vs. 22%, p = 0.03), required more right ventricular assist device support (19% vs. 11% vs. 6%, p = 0.006), and had a higher risk of bleeding (p = 0001). Survival of CCMP patients was similar to that of other groups. Conclusions CCMP patients treated with MCS have survival similar to other MCS patients despite more frequent need for right ventricular assist device support and increased bleeding risk.
Objectives The goals of this study were to determine: 1) if low-risk patients assessed by a CHADS2 score, a clinical scoring system quantifying a risk of stroke in patients with atrial fibrillation ...(AF), require a routine screening transesophageal echocardiogram (TEE) before pulmonary vein isolation (PVI); and 2) the relationship of a CHADS2 score with left atrial (LA)/left atrial appendage (LAA) spontaneous echo contrast, sludge, and thrombus. Background There is no clear consensus of whether a screening TEE before catheter ablation of AF should be performed in every patient. Methods Initial TEEs for pre-PVI of 1,058 AF patients (age 57 ± 11 years, 80% men) were reviewed and compared with a CHADS2 score. Results CHADS2 scores of 0, 1, 2, 3, 4, 5, and 6 were present in 47%, 33%, 14%, 5%, 1%, 0.3%, and 0% of patients, respectively. The prevalence of LA/LAA thrombus, sludge, and spontaneous echo contrast were present in 0.6%, 1.5%, and 35%. The prevalence of LA/LAA thrombus/sludge increased with ascending CHADS2 score (scores 0 0%, 1 2%, 2 5%, 3 9%, and 4 to 6 11%, p < 0.01). No patient with a CHADS2 score of 0 had LA/LAA sludge/thrombus. In a multivariate model, history of congestive heart failure and left ventricular ejection fraction <35% were significantly associated with sludge/thrombus. Conclusions The prevalence of LA/LAA sludge/thrombus in patients with AF undergoing a pre-PVI screening TEE is very low (<2%) and increases significantly with higher CHADS2 scores. This suggests that a screening TEE before PVI should be performed in patients with a CHADS2 score of ≥1, and in patients with a CHADS2 score of 0 when the AF is persistent and therapeutic anticoagulation has not been maintained for 4 weeks before the procedure.
Abstract Background Venous thromboembolism chemoprophylaxis remains underutilized in hospitalized medical patients at high risk for venous thromboembolism. We assessed the effect of a healthcare ...quality improvement initiative comprised of a targeted electronic alert, comparative practitioner metrics, and practitioner-specific continuing medical education on the rate of appropriate venous thromboembolism chemoprophylaxis provided to medical inpatients at high risk for venous thromboembolism. Methods We performed a multicenter prospective observational cohort study in an urban Utah hospital system. All medical patients admitted to one of two participating hospitals from 1 April 2010 to 31 December 2012 were eligible. Patients were members of the “control” (1 April 2010 to 31 December 2010), “intervention” (1 January 2011 to 31 December 2011), or “subsequent year” (1 January 2012 to 31 December 2012) group. The primary outcome was the rate of appropriate chemoprophylaxis among patients at high risk for venous thromboembolism. Secondary outcomes included rates of symptomatic venous thromboembolism, major bleeding, all-cause mortality, heparin-induced thrombocytopenia, physician satisfaction, and alert fatigue. Results The rate of appropriate chemoprophylaxis among patients at high risk for venous thromboembolism increased (66.1% control period vs. 81.0% intervention period vs 88.1% subsequent year; p<0.001 for each comparison). A significant reduction of 90 day symptomatic venous thromboembolism accompanied the quality initiative (9.3% control period, 9.7% intervention period, 6.7% subsequent year; p=0.009); 30 day venous thromboembolism rates also significantly declined. Conclusions A multifaceted intervention was associated with increased appropriate venous thromboembolism chemoprophylaxis among medical inpatients at high risk for venous thromboembolism and reduced symptomatic venous thromboembolism. The effect of the intervention was sustained.
The recent initiation of screening protocols and greater utilization of computed tomography has led to an increasing proportion of non-small cell lung cancer (NSCLC) patients presenting with ...subcentimeter stage IA tumors. The aim of this study was to compare the oncologic outcomes of lobectomy, segmentectomy, and wedge resection in patients with NSCLC tumors 1 cm or less in diameter.
Data were extracted from medical records of patients undergoing surgical resection for stage IA NSCLC and a pathologically confirmed tumor diameter measuring 1 cm or less. Primary oncologic outcomes were disease recurrence and disease-free survival. Statistical comparisons were performed using Fisher's exact test and unpaired t test. Kaplan-Meier curves were compared using the log rank test. Significance was defined as a two-tailed p value less than 0.05.
A total of 107 patients underwent complete (R0) surgical resection for stage IA NSCLC 1 cm or less in diameter (lobectomy, 32; segmentectomy, 40; wedge, 35). Age, sex distribution, tumor size, and histology were similar between groups. There was 1 perioperative mortality in the lobectomy group (3%). At a mean follow-up of 42.5 months, overall disease recurrence was equivalent, occurring in 3 lobectomy patients (9%), 4 segmentectomy patients (10%), and 3 wedge resection patients (9%; p=0.99). Estimated 5-year disease-free survival was comparable among cohorts (lobectomy, 87%; segmentectomy, 89%; wedge, 89%; p>0.402).
Sublobar resections are associated with oncologic outcomes that are comparable to those of lobectomy for subcentimeter stage IA NSCLC, suggesting that they may be appropriate surgical interventions in this patient cohort. The validity of these observations needs to be assessed in a prospective setting.
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