Individualized Prediction for Risk of Recurrence in Stage I/II Melanoma Patients With Negative Sentinel Lymph Node.

Background: Despite the favorable prognosis of AJCC stage I/II melanoma patients, up to 20%-30% will develop metastases. Our objective is to predict long-term risk (probability) of recurrence in early-stage melanoma patients.

Methods: A Risk Score to predict long-term recurrence was developed using Cox regression based on 2668 patients.

Propensity scores used as overlap weights provide exact covariate balance.

Overlap weighting, using weights defined as the probability of receiving the opposite treatment, is a relatively new, alternative propensity score-based weighting technique used to adjust for confounding when estimating causal treatment effects. It has preferable properties compared to inverse probability of treatment weighting, such as exact covariate balance, safeguards against extreme weights and emphasis on medical equipoise, where treatment decisions are most uncertain. In this article, we introduce the overlap weighting methodology, compare it to inverse probability of treatment weighting and provide some strategies for assessing weighting impact, through an applied example of hospital mortality.

A simplified pneumonia severity index (PSI) for clinical outcome prediction in COVID-19.

Background: The Pneumonia Score Index (PSI) was developed to estimate the risk of dying within 30 days of presentation for community-acquired pneumonia patients and is a strong predictor of 30-day mortality after COVID-19. However, three of its required 20 variables (skilled nursing home, altered mental status and pleural effusion) are not discreetly available in the electronic medical record (EMR), resulting in manual chart review for these 3 factors. The goal of this study is to compare a simplified 17-factor version (PSI-17) to the original (denoted PSI-20) in terms of prediction of 30-day mortality in COVID-19.

Characterization of Lymph Node Tumor Burden in Node-Positive Prostate Cancer Patients after Robotic-Assisted Radical Prostatectomy with Extended Pelvic Lymph Node Dissection.

Background: Prostate cancer (PCa) nodal staging does not account for lymph node (LN) tumor burden. The LN anatomical compartment involved with the tumor or the quantified extent of extranodal extension (ENE) have not yet been studied in relation to biochemical recurrence-free survival (BRFS).

Methods: Histopathological slides of 66 pN1 PCa patients who underwent extended pelvic lymph node dissection were reviewed.

Impact of Adherence to Operative Standards and Stage-Specific Guideline-Recommended Therapy in Nonmetastatic Pancreatic Adenocarcinoma.

Background: Achieving optimal surgical outcomes in pancreatic adenocarcinoma requires a combination of both curative-intent resection to oncologic standards and stage-specific neoadjuvant or adjuvant therapy. This investigation sought to examine factors associated with receipt of standard-adherent surgery (SAS) and guideline-recommended therapy (GRT) and determine the impact of compliance on patient survival.

Patients And Methods: From the 2006-2016 National Cancer Database, 21,304 patients underwent resection for nonmetastatic pancreatic adenocarcinoma.

Impact of Mediating and Confounding Variables on the Volume-Outcome Association in the Treatment of Pancreatic Cancer.

Background: High-volume centers (HVC), academic centers (AC), and longer travel distances (TD) have been associated with improved outcomes for patients undergoing surgery for pancreatic adenocarcinoma (PAC). Effects of mediating variables on these associations remain undefined. The purpose of this study is to examine the direct effects of hospital volume, facility type, and travel distance on overall survival (OS) in patients undergoing surgery for PAC and characterize the indirect effects of patient-, disease-, and treatment-related mediating variables.

Clinical Factors and Outcomes When Real-World Heart Teams Overruled STS Risk Scores in TAVR Cases.

Objectives: This study was conducted to determine why heart teams recommended transcatheter aortic valve replacement (TAVR) versus surgical AVR (SAVR) for patients at low predicted risk of mortality (PROM) and describe outcomes of these cases.

Background: Historically, referral to TAVR was based predominately on the Society of Thoracic Surgeons (STS) risk model's PROM >3%. In selected cases, heart teams had latitude to overrule these scores.

Preoperative Risk Prediction for Pancreatectomy: A Comparative Analysis of Three Scoring Systems.

Introduction: Pancreatectomy is associated with high morbidity and mortality. Therefore, patient selection and risk prediction is paramount. In this study, three validated perioperative risk scoring systems were compared among patients undergoing pancreatectomy to identify the most clinically useful model.

The CUSUM Slope Equals Observed Minus Expected Mortality and Can Be Visualized by a "Slope-Meter".

We present an additional advantage of the Risk-Adjusted CUSUM (RA-CUSUM), namely, that its slope can be quantified and is in fact equivalent to Observed (O) minus Expected (E) mortality. That is, the height of the RA-CUSUM is the O minus E deaths, which measures performance since the start of the series, and the slope of the RA-CUSUM is the O minus E mortality which measures performance during a chosen interval. We present a useful graphical tool (Slope-Meter) to allow approximation of this mortality difference by the viewer.

Comparison of 26-mm Evolut and 23-mm Sapien 3 Valves in TAVR for Small Aortic Annulus.

Background: Patients with small aortic annuli (SAA) are prone to higher post-transcatheter aortic valve replacement (TAVR) transvalvular gradients and development of prosthesis-patient mismatch (PPM). In many patients with SAA, the choice of TAVR valve commonly involves choosing between the 26-mm Medtronic Evolut 2 (ME26) or the 23-mm Edwards Sapien 3 valve (ES23). We compared echocardiographic and clinical outcomes in patients with SAA undergoing TAVR with either valve.

Calibration Factors for STS Risk Model Predictions: Why, How and When They Are Used.

The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database is the world's premier adult cardiac surgery outcomes registry. This tutorial explains the following: how STS updates the risk models that are used to calculate the predicted risks of adverse events in the registry; why STS on a quarterly basis adjusts or "calibrates" the observed-to-expected ratios to equal 1 (O/E = 1), thereby effectively making the annual number of adverse events predicted by the model match the annual number of adverse events observed in the entire registry; the differences between the calibrated and uncalibrated O/E ratios; and how and when to use each.

Remdesivir and Mortality in Patients With Coronavirus Disease 2019.

Background: The impact of remdesivir (RDV) on mortality rates in coronavirus disease 2019 (COVID-19) is controversial, and the mortality effect in subgroups of baseline disease severity has been incompletely explored. The purpose of this study was to assess the association of RDV with mortality rates in patients with COVID-19.

Methods: In this retrospective cohort study we compared persons receiving RDV with those receiving best supportive care (BSC).

Is the 21-Gene Recurrence Score on Core Needle Biopsy Equivalent to Surgical Specimen in Early-Stage Breast Cancer? A Comparison of Gene Expression Between Paired Core Needle Biopsy and Surgical Specimens.

Background: Molecular testing on surgical specimens predicts disease recurrence and benefit of adjuvant chemotherapy in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early-stage breast cancer (EBC). Testing on core biopsies has become common practice despite limited evidence of concordance between core/surgical samples. In this study, we compared the gene expression of the 21 genes and the recurrence score (RS) between paired core/surgical specimens.

Continuous Monitoring of Risk-Adjusted Outcomes: Excess Deaths vs Lives Saved.

Reporting of risk-adjusted surgical outcomes is commonly used to compare providers and track changes over time. Preferred graphical methods use the relationship of the observed to the expected values of outcome events, including their ratio (O/E), and the cumulative sum (CUSUM) of their differences over time, called Risk-Adjusted CUSUM (RA-CUSUM) or Variable Life Adjusted Display (VLAD). We demonstrate these methods using operative mortality data for 7255 isolated coronary artery bypass graft patients from January 2014 to June 2017.

Multiplex immunofluorescence to measure dynamic changes in tumor-infiltrating lymphocytes and PD-L1 in early-stage breast cancer.

Background: The H&E stromal tumor-infiltrating lymphocyte (sTIL) score and programmed death ligand 1 (PD-L1) SP142 immunohistochemistry assay are prognostic and predictive in early-stage breast cancer, but are operator-dependent and may have insufficient precision to characterize dynamic changes in sTILs/PD-L1 in the context of clinical research. We illustrate how multiplex immunofluorescence (mIF) combined with statistical modeling can be used to precisely estimate dynamic changes in sTIL score, PD-L1 expression, and other immune variables from a single paraffin-embedded slide, thus enabling comprehensive characterization of activity of novel immunotherapy agents.

Methods: Serial tissue was obtained from a recent clinical trial evaluating loco-regional cytokine delivery as a strategy to promote immune cell infiltration and activation in breast tumors.

Trends in Diagnosis Related Groups for Inpatient Admissions and Associated Changes in Payment From 2012 to 2016.

Importance: Hospitals are reimbursed based on Diagnosis Related Groups (DRGs), which are defined, in part, by patients having 1 or more complications or comorbidities within a given DRG family. Hospitals have made substantial investment in efforts to document these complications and comorbidities.

Objective: To examine temporal trends in DRGs with a major complication or comorbidity, compare these findings with 2 alternative measures of disease severity, and estimate associated changes in payment.

Development of a Risk Score and Nomogram to Predict Individual Benefit Attained from the Addition of Adjuvant Chemotherapy in the Treatment of Stage II Colon Cancer.

Background: Current guidelines recommend considering adjuvant chemotherapy (AC) for stage II colon cancer (CC) with poor prognostic clinicopathologic and molecular features. However, the relative impact of individual or constellations of high-risk features remains undefined. We developed an individualized point-of-care tool to predict survival benefit attained from the addition of AC.

Early cost-utility analysis of tissue-engineered heart valves compared to bioprostheses in the aortic position in elderly patients.

Objectives: Aortic valve disease is the most frequent indication for heart valve replacement with the highest prevalence in elderly. Tissue-engineered heart valves (TEHV) are foreseen to have important advantages over currently used bioprosthetic heart valve substitutes, most importantly reducing valve degeneration with subsequent reduction of re-intervention. We performed early Health Technology Assessment of hypothetical TEHV in elderly patients (≥ 70 years) requiring surgical (SAVR) or transcatheter aortic valve implantation (TAVI) to assess the potential of TEHV and to inform future development decisions.

Long-Term Durability of Transcatheter Valves: The Importance of Accurate Data.

As transcatheter valves are offered to progressively lower-risk patients, it is increasingly important to have accurate data about durability. Structural valve deterioration (SVD) implies an adverse change in the morphology of the leaflets and function of the valve compared with the state at implantation. However, a recent European statement allows SVD to be defined solely by a threshold mean gradient ≥20 mm Hg.

Reduction in coronary artery bypass grafting surgery mortality and morbidity during a 3-year multicenter quality improvement project.

Objective: Risk-adjusted operative mortality is a key quality measure for isolated coronary artery bypass grafting. Through a multicenter quality improvement initiative, we sought to improve this measure at 14 surgical programs within a large and geographically dispersed health care system.

Methods: Observed mortality and combined mortality/morbidity rates for isolated coronary artery bypass grafting were collected from January 2014 to June 2017.

Resectable Distal Pancreas Cancer: Time to Reconsider the Role of Upfront Surgery.

Background: Neoadjuvant chemotherapy (NAC) is increasingly utilized to optimize survival in proximal pancreatic adenocarcinoma. However, few studies have explored the impact of NAC in distal pancreas cancer.

Methods: Patients with resectable pancreatic adenocarcinoma of the body or tail treated with either upfront pancreatectomy or NAC followed by surgery were identified in the 2006-2014 National Cancer Database.

Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors.

Identifying tumor antigen-specific T cells from cancer patients has important implications for immunotherapy diagnostics and therapeutics. Here, we show that CD103CD39 tumor-infiltrating CD8 T cells (CD8 TIL) are enriched for tumor-reactive cells both in primary and metastatic tumors. This CD8 TIL subset is found across six different malignancies and displays an exhausted tissue-resident memory phenotype.