Development and validation of a population based risk algorithm for obesity: The Obesity Population Risk Tool (OPoRT)

<div><p>Background</p><p>Given the dramatic rise in the prevalence of obesity, greater focus on prevention is necessary. We sought to develop and validate a population risk tool for obesity to inform prevention efforts.</p><p>Methods</p><p>We developed the Obesity Population Risk Tool (OPoRT) using the longitudinal National Population Health Survey and sex-specific Generalized Estimating Equations to predict the 10-year risk of obesity among adults 18 and older. The model was validated using a bootstrap approach accounting for the survey design. Model performance was measured by the Brier statistic, discrimination was measured by the C-statistic, and calibration was assessed using the Hosmer-Lemeshow Goodness of Fit Chi Square (HL χ²).</p><p>Results</p><p>Predictive factors included baseline body mass index, age, time and their interactions, smoking status, living arrangements, education, alcohol consumption, physical activity, and ethnicity. OPoRT showed good performance for males and females (Brier 0.118 and 0.095, respectively), excellent discrimination (C statistic ≥ 0.89) and achieved calibration (HL χ² <20).</p><p>Conclusion</p><p>OPoRT is a valid and reliable algorithm that can be applied to routinely collected survey data to estimate the risk of obesity and identify groups at increased risk of obesity. These results can guide prevention efforts aimed at reducing the population burden of obesity.</p></div

Descriptive characteristics of the cohort at baseline.

<p>Descriptive characteristics of the cohort at baseline.</p

Obesity Population Risk Tool (OPoRT) Internal validation characteristics for males and females.

<p>Obesity Population Risk Tool (OPoRT) Internal validation characteristics for males and females.</p

Obesity Population Risk Tool (OPoRT) function for males and females.

<p>Obesity Population Risk Tool (OPoRT) function for males and females.</p

Calibration plot demonstrating the relationship between predicted and observed risk among females.

<p>Calibration plot demonstrating the relationship between predicted and observed risk among females.</p

Nodal yield <15 is associated with reduced survival in esophagectomy and is a quality metric

Background: Surgical resection after neoadjuvant therapy remains the cornerstone of curative management of esophageal adenocarcinoma and is frequently used for squamous cell carcinoma. The optimal extent of lymphadenectomy and whether increasing lymph node yields confer a survival benefit remains unclear. Guidelines suggest resecting and examining a minimum of 15 lymph nodes at esophagectomy. This study assessed the impact of lymph node yield and lymph node ratio (LNR) on survival, identifying factors influencing nodal yield and radicality of resection. Methods: All patients undergoing esophagectomy with curative intent at a single institution (stage 1-4 inclusive) from January 1, 2010, to December 31, 2020, were reviewed. Clinical and pathologic variables were interrogated. LNR was calculated by dividing positive lymph nodes by the total nodes resected. Results: Esophagectomy was performed in 397 patients, with 288 undergoing minimally invasive esophagectomy (MIE). Margin status (hazard ratio [HR], 1.80; 95% CI, 1.15-2.83; P Conclusions: Textbook lymphadenectomy is associated with improved survival. Low lymph node yield and a high LNR are associated with reduced overall survival. A LNR of <0.05 is associated with significant survival benefit. A minimum nodal yield of 15 should remain the standard of care.</p

Nodal yield <15 is associated with reduced survival in esophagectomy and is a quality metric

Background: Surgical resection after neoadjuvant therapy remains the cornerstone of curative management of esophageal adenocarcinoma and is frequently used for squamous cell carcinoma. The optimal extent of lymphadenectomy and whether increasing lymph node yields confer a survival benefit remains unclear. Guidelines suggest resecting and examining a minimum of 15 lymph nodes at esophagectomy. This study assessed the impact of lymph node yield and lymph node ratio (LNR) on survival, identifying factors influencing nodal yield and radicality of resection. Methods: All patients undergoing esophagectomy with curative intent at a single institution (stage 1-4 inclusive) from January 1, 2010, to December 31, 2020, were reviewed. Clinical and pathologic variables were interrogated. LNR was calculated by dividing positive lymph nodes by the total nodes resected. Results: Esophagectomy was performed in 397 patients, with 288 undergoing minimally invasive esophagectomy (MIE). Margin status (hazard ratio [HR], 1.80; 95% CI, 1.15-2.83; P Conclusions: Textbook lymphadenectomy is associated with improved survival. Low lymph node yield and a high LNR are associated with reduced overall survival. A LNR of <0.05 is associated with significant survival benefit. A minimum nodal yield of 15 should remain the standard of care.</p

γ-H2AX formation pre- and post- high dose BLM treatment assessed by flow cytometry.

<p>Experiments were run in triplicate. Cells were subject to high dose BLM exposure (corresponding to ten times their respective maintenance concentrations) for 24 hours. Flow cytometric detection of BLM-induced γ-H2AX foci formation were then obtained in a subset of four cell lines (ACHN, HOP, NCCIT and H322M). * P<0.05 for comparison between cell lines prior and after high dose BLM treatment. All parental lines exhibited significant increase in formation of γ-H2AX. # P<0.05 for comparison between parental and resistant cell lines at baseline (pre-treatment). One of four BLM-resistant cell lines (NCCIT_1.5) had greater γ-H2AX formation than its parental counterpart at baseline. & P<0.05 for comparison between resistant and parental cell lines following BLM treatment. Two of four BLM-resistant cell lines (HOP_0.1 and NCCIT1._5.) revealed significantly less γ-H2AX formation than their parental counterparts post BLM treatment, with a third line (H322M_2.5) being borderline significant (p=0.054).</p

Percent cell apoptosis pre- and post- high dose BLM exposure in four parental/resistant cell line pairs.

<p>* P<0.05 for comparison between cell lines prior to and after high dose BLM treatment. All parental lines but no resistant lines exhibited significant increases in apoptosis post- BLM treatment. & P<0.05 for comparison between resistant and parental cell line following BLM treatment. Less cell apoptosis was found in three (HOP_0.05, NCCIT_1.5, and H322M_2.5) of four BLM-resistant lines, when compared to their parental lines.</p

Effects of 3-week discontinuation of maintenance BLM treatment on IC₅₀ (µg/ml).

<p>Experiments were performed in triplicate. Log IC₅₀ comparisons were performed. Three (HOP_0.05, NT2_0.1, and NCCIT_1.5) of the seven cell lines had significant reductions in IC₅₀ values following three weeks of BLM-free maintenance. * P<0.05 for comparisons between BLM resistant sub-clones and their corresponding counterparts with three weeks of treatment break. </p