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Differences in presenting symptoms of primary hyperparathyroidism and outcomes of parathyroidectomy between sexes have been described, but whether these can be assessed by perioperative use of a validated tool, such as the Pasieka Parathyroidectomy Assessment Score, is unknown. All patients with primary hyperparathyroidism were asked to complete symptom assessment at the preoperative and postoperative visits. The assessment included a query for 13 Pasieka Parathyroidectomy Assessment Score parameters evaluated using a visual analog scale as described by Pasieka (summative score 0–1,300), and general quality of life and wellness. A review of a prospectively maintained database of primary hyperparathyroidism patients (January 2016–December 2019) was performed, and those who had a 6-month cure after initial parathyroidectomy were included. The study cohort was mostly women (77%, 541/701). The median preoperative Pasieka Parathyroidectomy Assessment Score was higher in women (155, 0–1,190) than in men (80.5, 0–855, P <.001), although there were similar rates of asymptomatic primary hyperparathyroidism (Pasieka Parathyroidectomy Assessment Score = 0, 12.5% vs 7%, P =.042). After curative parathyroidectomy, women reported a substantial reduction in symptomatology, with Pasieka Parathyroidectomy Assessment Score declining by 35% at initial postoperative visit (median, 155 vs 100, P <.001), further decreasing to 48% by 6 months (155 vs 80, P <.001). The Pasieka Parathyroidectomy Assessment Score in men did change but to a much smaller degree at both the initial postoperative visit (80.5 vs 70; P =.036) and at 6 months (80.5 vs 57.5; P =.048). When assessed with the Pasieka Parathyroidectomy Assessment Score, improvement in symptoms was clearly demonstrated for women after curative parathyroidectomy. Whether symptom improvement also occurs in men is less apparent but may be due to disparities in the development and validation of outcomes tools in general. [ABSTRACT FROM AUTHOR]

The American College of Radiology Thyroid Imaging Reporting and Data System for ultrasound classification of malignancy risk was developed to better triage thyroid nodules for fine-needle aspiration biopsy. To examine further, we compared thyroid cytologic classification rates in nodules before and after institutional Thyroid Imaging Reporting and Data System implementation. Cytology diagnoses by Bethesda criteria (categories I–VI) from January 2014 to October 2021 were retrieved; observed changes in yearly category frequency were analyzed by linear regression; and pooled cohorts of pre– (2014–2018) and post–Thyroid Imaging Reporting and Data System (2019–2021) cytology call rates were compared. Overall, 7,413 cytologic specimens were included (range/year 715–1,444). From 2014 to 2021, the proportion of benign (Bethesda category II) diagnosis per year declined stepwise from 49.7% to 19.4%, and atypia of undetermined significance/follicular lesion of undetermined significance (Bethesda category III) increased sequentially from 21.3% to 51.5%. Between 2014 and 2021, Bethesda category III diagnosis increased on average by 4.8% per year (95% confidence internal, 3.29–5.54; P <.001) and Bethesda category II results decreased on average by 4.4% per year (95% confidence interval, 6.29–3.42; P <.001). When comparing pre– and post–Thyroid Imaging Reporting and Data System, the proportion of Bethesda category II cytology results decreased (43.1% vs 21%; P =.001) while Bethesda category III (28.3% vs 47.7%; P =.002) and Bethesda category V (1.1% vs 1.7%; P =.015) results increased. After implementation of American College of Radiology Thyroid Imaging Reporting and Data System ultrasound criteria, we observed a 2.5-fold decline in the rate of benign cytology and an increase in the proportion of atypia of undetermined significance/follicular lesion of undetermined significance results. [ABSTRACT FROM AUTHOR]

Molecular testing improves the diagnostic accuracy of thyroid cancer. Whether specific molecular testing results are associated with tumor phenotype or provide prognostic information needs further delineation. Consecutive thyroid cancer patients after index thyroidectomy with ThyroSeq version 3 (Rye Brook, NY) molecular testing obtained on preoperative fine-needle aspiration or thyroidectomy specimens from patients with thyroid cancer were categorized into 3 molecular risk groups based on detected mutations, fusions, copy number alterations, and/or gene expression alterations and correlated with histopathology and recurrence, defined as biochemical or structural. Of 578 patients, 49.9%, 37.5%, and 12.6% had molecular risk group–low, molecular risk group–intermediate, and molecular risk group–high cancers, respectively. With a median 19-month follow-up, 9.1% patients recurred. Compared with molecular risk group–low, molecular risk group–intermediate cancers were diagnosed in younger patients and more often had microscopic extrathyroidal extension, involved margins, and nodal disease. Compared with molecular risk group–intermediate, molecular risk group–high cancers were diagnosed in older patients and more often had gross extrathyroidal extension and vascular invasion. In multivariable analysis, recurrence was more likely in molecular risk group–high cancers than in molecular risk group–intermediate (hazard ratio = 4.0; 95% confidence interval, 1.9–8.6; P <.001) and more likely in molecular risk group–intermediate than in molecular risk group–low (hazard ratio = 5.0; 95% confidence interval, 2.0–12.5; P <.001). Using modern comprehensive genotyping, the genetic profile of thyroid cancers can be categorized into 3 novel molecular risk groups that were associated with histopathologic phenotype and recurrence in short-term follow-up. [ABSTRACT FROM AUTHOR]

Robotic-assisted pancreatectomy continues to proliferate despite limited evidence supporting its benefits from the patient's perspective. We compared patient-reported outcomes (PROs) between patients undergoing robotic and open pancreatectomies. PROs, measured with the FACT-Hep, FACT-G, and HCS, were assessed in the immediate postoperative (i.e., preoperative to discharge) and recovery (i.e., discharge to three months postoperative) periods. Linear mixed models estimated the association of operative approach on PROs. Minimally important differences (MIDs) were also considered. Among 139 patients, 105 (75.5%) underwent robotic pancreatectomies. Compared to those who underwent open operations, those who underwent robotic operations experienced worse FACT-Hep scores that were both statistically and clinically significant (mean difference [MD] 8.6 points, 95% CI 1.0–16.3). Declines in FACT-G (MD 4.3, 95% CI −1.0 to 9.6) and HCS (MD 4.3, 95% CI 0.8–7.9) scores appeared to contribute equally in both operative approaches to the decline in total FACT-Hep score. Patients who underwent robotic versus open operations both statistically and clinically significantly improved due to improvements in HCS (MD 6.1, 95% CI 2.3–9.9) but not in FACT-G (MD 1.2, 95% CI − 5.1-7.4). The robotic approach to pancreas surgery might offer, from the patient's perspective, greater improvement in symptoms over the open approach by three months postoperatively. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to sample the opinions of radiation oncologists and trainees in the United States regarding residency expansion, what action(s) should be taken to limit residency supply, if any, and the proposed Accreditation Council for Graduate Medical Education (ACGME) changes.Methods and Materials: An online survey was distributed to 1048 attending radiation oncologists by e-mail and approximately 800 residents through their program coordinators. The survey asked respondents to rank how strongly they agreed with certain statements regarding residency supply, possible solutions to address any perceived oversupply, and the proposed ACGME changes on a 1-to-10 disagreement-to-agreement scale. The 16% response rate yielded 294 responses for analysis.Results: Of the respondents, 90 (30%) were residents, and 204 (70%) were attendings, of whom 117 (57%) were academic and 87 (43%) were nonacademic. Eighty-six percent agreed that there is a residency oversupply issue, and 91% agreed that actions should be taken to limit residency expansion. On χ2 test, residents and attendings were similarly likely to agree that there is a residency oversupply issue (93% and 89%, P = .27), although residents were more likely to agree that this oversupply should be acted upon compared with attendings (100% and 88%, P < .01). Regarding possible solutions, respondents were most likely to agree that further expansion should be limited (90%), program requirements should be made more stringent (76%), and the use of the Supplemental Offer and Acceptance Program should be limited (69%). Proposed ACGME changes that respondents were most likely to agree with included requiring that programs have modern image guidance, stereotactic radiation therapy, and brachytherapy techniques (98%) and have 4+ faculty members and maintain a faculty-to-resident ratio of >1.5:1 (86%). Case log minimums most supported to be increased were 4 uterus (65%) and 11 postmastectomy breast (61%) simulations.Conclusions: The majority of respondents agree that there is a residency oversupply issue and that actions should be taken to limit residency expansion and make program requirements more stringent. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate for age, racial, and ethnic disparities among clinical studies where patients can potentially receive brachytherapy treatment. Trials involving brachytherapy for breast, cervical, prostate, and uterine cancers were identified using ClinicalTrials.gov. The age, racial, and ethnic breakdown of the identified trials were compared to US population-estimates derived from the Surveillance, Epidemiology, and End Results (SEER) Program. Primary outcomes were gaps between gaps between mean age and race and ethnic proportions in trials and the US population. Secondary outcomes included proportions of racial and ethnic data reporting. Descriptive statistics, t-tests, χ2 tests, and univariate analysis were used to analyze the data. A total of 77 trials with reported data were identified, representing 13,580 patients. The overall difference in mean age in the identified trials compared to US population estimates was -2.29 years (p < 0.001), with the largest difference occurring in prostate cancer at -2.72 years (p < 0.001). With the exception of ethnicity in cervical cancer (p = 0.18), all racial and ethnic distributions were statistically significantly different. Overall, the largest disparity was among Asian (-2.65%) and Hispanic patients (-1.05%). Of the 77 trials, 76 (98.7%) reported age, 36 (46.8%) reported race, and 24 (31.2%) reported ethnicity. Diversity data is underreported among clinical studies where brachytherapy is a potential treatment component. However, among reported trials, disparities are present albeit relatively small compared to previous studies reporting on disparities in clinical trials. Future efforts should emphasize increased reporting of racial and ethnicity data as well as ensuring inclusion of older patients and minorities. [ABSTRACT FROM AUTHOR]

• APBI use is stable since 2008, but with a drop in brachytherapy and a rise in IORT. • There is a steady rise in patients considered "suitable" by ASTRO APBI guidelines. • Trends in APBI modality utilization appears to be influenced by available literature. To examine recent modality utilization trends in accelerated partial breast irradiation (APBI) in the National Cancer Database (NCDB) based on the American Society for Radiation Oncology (ASTRO) guidelines. A total of 58,194 patients treated with APBI were identified. Patients were segregated by APBI modality (brachytherapy, external beam radiotherapy [EBRT], and intraoperative radiotherapy ([IORT]). These patients were then further classified by suitability to receive APBI based on ASTRO guidelines. Temporal trends in utilization were evaluated using linear regression. Logistic regression was applied to study factors contributing to APBI modality choice and treatment within the ASTRO suitability groups. Patients treated with brachytherapy, EBRT, and IORT comprised 70.5%, 17.5%, and 12.0% of patients treated with APBI. From 2008 to 2017, total APBI cases remained relatively stable (−54.1 cases/year, p = 0.161) while brachytherapy cases decreased by 258.7 cases/year (p < 0.001). EBRT and IORT increased by 51.5 cases/year (p = 0.019) and 153.1 cases/year (p < 0.001), respectively. 40.0% of patients treated with APBI were classified as "suitable", which increased from 2010 to 2017 from 35.3% to 45.3% (slope = 1.51%/year, r 2 = 0.61, p = 0.022). In comparison, 36.0% (36.1% in 2010 to 33.1% in 2017) of patients were classified as "cautionary" (slope = −0.33%/year, r 2 = 0.63, p = 0.019) and 23.9% (28.6% in 2010 to 21.6% in 2017) of patients were classified as "unsuitable" (slope = −1.18%/year, r 2 = 0.67, p = 0.012). While overall APBI utilization has remained stable since 2008, this has been accompanied by a decline in brachytherapy and a rise in IORT. The causes of these trends should be the topic of future research. [ABSTRACT FROM AUTHOR]

Apolipoprotein M (ApoM) is a lipocalin produced by the liver that binds to high-density lipoprotein and sphingosine-1-phosphate in circulation. Reduced ApoM in plasma is associated with death and hospitalizations in patients with heart failure (HF). The syndrome of right heart failure (RHF) is also associated with increased level of inflammatory cytokines, in part due to liver and splanchnic congestion. To date, the relationship between ApoM and inflammation in RHF has not been investigated. In this study, we evaluated the impact of RHF on ApoM levels and assessed the correlation between ApoM and multiple circulating cytokines and growth factors. We hypothesized that ApoM levels would be significantly decreased in patients with RHF and would inversely correlate with markers of inflammation. We recruited adult patients undergoing right heart catheterization and excluded those with history of transplant, inflammatory disease, or malignancy. Patients underwent simultaneous blood sampling from hepatic vein and IVC and were classified into normal, HF, and RHF cohorts based on established hemodynamic criteria a priori. ApoM levels in serum were quantified by a validated ELISA and cytokines and growth factors were assessed using multiplex protein assay. A mouse model of RHF was established using pulmonary artery banding (PAB) and circulating ApoM levels were measured at 2 months after PAB. A total of 61 patients were recruited. HF and RHF patients had similar cardiac indices, although RHF patients had higher right atrial pressure (RAP) and higher RAP/pulmonary capillary wedge pressure ratio. ApoM was decreased in HF and RHF patients in a stepwise manner compared to normal controls (p=0.02 and 0.05 respectively, Figure). Using a multiplex protein assay, we identified a distinct inflammatory profile in the RHF population, including elevation of novel factors such as VEGF-A, soluble CD163 (sCD163), and CXCL12. Correlational analysis showed that ApoM was inversely correlated with several inflammatory biomarkers, with the strongest association seen with sCD163 (R=-0.53, p<0.001). Moreover, we found that PAB in mice reduced ApoM levels by 60% compared to controls (p=0.05) and tissue analysis showed upregulation of inflammatory and profibrotic pathways. RHF is associated with a profound reduction in ApoM levels when compared to both normal patients and those with HF and preserved right ventricular function. Circulating ApoM was found to be inversely correlated with multiple inflammatory biomarkers. In a mouse model of RHF, ApoM levels were decreased early in the disease process suggesting this response may be an initiating event. Future studies will investigate the mechanisms and consequences of reduced levels of ApoM in patients with RHF. [ABSTRACT FROM AUTHOR]

• The PD controller design problem of positive discrete-time systems with constant delay is tackled in this work. • A systematic formulation is proposed to design non-fragile PD controllers for such kind of systems. • Based on the necessary and sufficient conditions derived, two tractable linear-programming-based and semi-definite-programming-based algorithms are developed for calculating the solution. This paper addresses the issue of proportional-derivative (PD) controllers design for positive linear systems in the discrete-time domain, which still remains a challenging problem in positive systems theory. The specific aim is to design a PD controller for a system with constant time delay, which simultaneously ensures closed-loop system stability and preserves positivity. Moreover, additive gain variation of the controller is considered in the synthesis process. Systematic formulation and tractable algorithms are developed to find the PD controller gains for positive stabilization. The performance of such methods is validated by numerical examples. [ABSTRACT FROM AUTHOR]

With the recent success of immunotherapy, there is a growing interest in combining radiation with immunotherapy to boost abscopal response rates. Several challenges exist in determining how to synergize these two modalities in the treatment of metastatic NSCLC. References for this review were identified through searches of MEDLINE/PubMed and Clinicaltrials.gov databases with the search terms "abscopal", "radiation OR radiotherapy," "NSCLC", and "lung" on the index date of July 2022 from 2000-2022. This systematic review focuses primarily on clinical papers. Early work combining radiotherapy with immunotherapy show promise in unlocking the abscopal effect. Preliminary evidence suggests that radiotherapy regimens with <5 fractions and smaller fields may be superior to regimens with 15 fractions and larger fields. There does not appear to be enough evidence to draw conclusions about the optimal timing of radiotherapy in relation to immunotherapy or the optimal anatomical location of radiation to induce the abscopal effect. Several studies suggest selecting patients with a higher absolute lymphocyte count (ALC) and lower neutrophil-to-lymphocyte ratio (NLR) may help to further boost abscopal response rates. Furthermore, selecting tumors with programmed death ligand-1 (PD-L1) expression, mismatch repair deficiency, and higher tumor mutational burden may similarly achieve this goal. Lastly, additional work is needed to minimize and predict for severe toxicity associated with combination therapy. [ABSTRACT FROM AUTHOR]

Purpose: To conduct an updated and comprehensive study on the risks of subsequent primary urogenital cancers for childhood and adolescent cancer survivors.Methods: This longitudinal study was conducted using 9 cancer registries from the Surveillance, Epidemiology and End Results (SEER) Program with follow-up from 1975 to 2017. There were 43,991 patients diagnosed with first primary cancer from 1975 to 2016 before the age of 20 years who subsequently survived for at least 1 year. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) for urogenital cancers were calculated.Results: Compared with the general population, the risk of urinary system cancer was significantly higher in both female (SIR = 5.18, 95% CI: 3.65-7.14) and male (SIR = 2.80, 95% CI: 1.94-3.92) survivors of any first cancer, with shorter median interval length between first cancer and subsequent urinary system cancer for male survivors (19.9 years) than female survivors (29.3 years). Females also had significantly higher SIR than males for subsequent urinary system cancer (SIRfemale:male=1.86, 95% CI: 1.13-3.03) and kidney cancer (SIRfemale:male = 1.97, 95% CI: 1.11-3.53). Compared with the general population, females with any first cancer had significantly higher risks for cancers of the corpus uteri (SIR = 2.32, 95% CI: 1.49-3.45) and vulva (SIR = 4.27, 95% CI: 1.38-9.95).Conclusions: Childhood and adolescent cancer survivors may have greater female susceptibility for developing subsequent urinary system and kidney cancers, and these survivors may have higher risks for specific types of reproductive system cancers. Our findings may lead to better awareness and surveillance for urogenital cancer by these cancer survivors and their physicians. [ABSTRACT FROM AUTHOR]

Dosimetric predictors of toxicity in patients treated with definitive chemoradiation for locally advanced non-small cell lung cancer are often identified through trial and error. This study used machine learning (ML) and explainable artificial intelligence to empirically characterize dosimetric predictors of toxicity in patients treated as part of a prospective clinical trial. A secondary analysis of the Radiation Therapy Oncology Group (RTOG) 0617 trial was performed. Multiple ML models were trained to predict grade ≥3 pulmonary, cardiac, and esophageal toxicities using clinical and dosimetric features. Model performance was evaluated using the area under the curve (AUC). The best performing model for each toxicity was explained using the Shapley Additive Explanation (SHAP) framework; SHAP values were used to identify relevant dosimetric thresholds and were converted to odds ratios (ORs) with confidence intervals (CIs) generated using bootstrapping to obtain quantitative measures of risk. Thresholds were validated using logistic regression. The best-performing models for pulmonary, cardiac, and esophageal toxicities, outperforming logistic regression, were extreme gradient boosting (AUC, 0.739), random forest (AUC, 0.706), and naive Bayes (AUC, 0.721), respectively. For pulmonary toxicity, thresholds of a mean dose >18 Gy (OR, 2.467; 95% CI, 1.049-5.800; P =.038) and lung volume receiving ≥20 Gy (V20) > 37% (OR, 2.722; 95% CI, 1.034-7.163; P =.043) were identified. For esophageal toxicity, thresholds of a mean dose >34 Gy (OR, 4.006; 95% CI, 2.183-7.354; P <.001) and V20 > 37% (OR, 3.725; 95% CI, 1.308-10.603; P =.014) were identified. No significant thresholds were identified for cardiac toxicity. In this data set, ML approaches validated known dosimetric thresholds and outperformed logistic regression at predicting toxicity. Furthermore, using explainable artificial intelligence, clinically useful dosimetric thresholds might be identified and subsequently externally validated. [ABSTRACT FROM AUTHOR]

• A significant unmet need for hepatitis B vaccination in adults remained in Viet Nam. • More people in the young age groups should be recommended for hepatitis B vaccination. • The social disparity in hepatitis B vaccination existed in various socioeconomic statuses. • Hepatitis B vaccination should be recommended for the broader population to achieve elimination. Gaps in adult hepatitis B vaccination were undefined in Vietnam, a lower-middle-income country. To address these gaps, this study defined hepatitis B vaccine coverage in adults and its associated factors in Ho Chi Minh City (HCMC), Viet Nam. We also proposed interventional strategies, prioritizing gap identification to facilitate hepatitis B elimination by 2030 and beyond. During 2019–2020, a multi-stage cluster serosurvey with probability proportional to size was conducted to representatively invite 20,000 adults (18 years or older) throughout HCMC for hepatitis B screening (HBsAg, anti-HBs, and anti-HBc). Serologic results defined two dependent variables: vaccine-induced immunity (i.e., isolated anti-HBs) and susceptibility (i.e., HBV naive). Associations of dependent variables with surveyed demographics, socioeconomic statuses, behaviors, and medical history at risk for hepatitis B were evaluated using weighted Poisson regression. The prevalence was 18.5% (95%CI, 17.3-20.0%) for vaccine-induced immunity and 37.7% (35.6-39.8%) for susceptibility. Even though analyses in the general population revealed a falling trend in vaccine-induced immunity prevalence from younger to older age groups, sensitivity analyses in the non-infected population (i.e., those who were both negative for HBsAg and anti-HBc) showed that younger age groups, especially those aged 30 to 50 years, had the lowest prevalence. Social inequalities existed in different ethnicities, residence areas, education levels, house ownership, and health insurance statuses. There was no significant association between vaccine-induced immunity or susceptibility and risky behaviors and medical histories. This study depicts a significant unmet need for hepatitis B vaccination in the general adult population in HCMC, Viet Nam. Indeed, the lack of vaccination was unevenly distributed regarding age groups, geographical areas, and socioeconomic statuses, which reveals profound social disparities. Therefore, to achieve hepatitis B elimination goals, besides the current recommendations for infants and risk-based strategies, hepatitis B vaccination should be recommended for the broader population. [ABSTRACT FROM AUTHOR]