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Simple Summary: Brachytherapy is a key component of radiation treatment in the curative treatment of locally advanced cervical cancer. To improve the delivery of brachytherapy, recent studies have explored the use of imaging, such as magnetic resonance imaging (MRI), in treatment planning. In this review, we reviewed the current evidence for image-guided brachytherapy and discussed future directions for research. Purpose: The standard of care for patients with locally advanced cervical cancer is definitive chemoradiation followed by a brachytherapy boost. This review describes the current status and future directions of image-guided adaptive brachytherapy for locally advanced cervical cancer. Methods: A systematic search of the PubMed and Clinicaltrials.gov databases was performed, focusing on studies published within the last 10 years. The search queried "cervical cancer [AND] image-guided brachytherapy [OR] magnetic resonance imaging (MRI) [OR] adaptive brachytherapy". Discussion: The retroEMBRACE and EMBRACE-I trials have established the use of MRI as the standard imaging modality for brachytherapy application and planning. Quantitative imaging and radiomics have the potential to improve outcomes, with three ongoing prospective studies examining the use of radiomics to further risk-stratify patients and personalize brachytherapy. Another active area of investigation includes utilizing the superior soft tissue contrast provided by MRI to increase the dose per fraction and decrease the number of fractions needed for brachytherapy, with several retrospective studies demonstrating the safety and feasibility of three-fraction courses. For developing countries with limited access to MRI, trans-rectal ultrasound (TRUS) appears to be an effective alternative, with several retrospective studies demonstrating improved target delineation with the use of TRUS in conjunction with CT guidance. Conclusions: Further investigation is needed to continue improving outcomes for patients with locally advanced cervical cancer treated with image-guided brachytherapy. [ABSTRACT FROM AUTHOR]

A dataset may exhibit multiple class labels for each observation; sometimes, these class labels manifest in a hierarchical structure. A textbook analogy would be that a book can be labelled as statistics as well as the encompassing label of non-fiction. To capture this behaviour in a model-based clustering context, we describe a model formulation and estimation procedure for performing clustering with nested Gaussian clusters in orthogonal intrinsic variable subspaces. We elucidate a two-stage clustering model, whereby the observed manifest variables are assumed to be a rotation of intrinsic primary and secondary clustering subspaces with additional noise subspaces. In a hierarchical sense, secondary clusters are presumed to be subclusters of primary clusters and so share Gaussian cluster parameters in the primary cluster subspace. An estimation procedure using the expectation-maximization algorithm is provided, with model selection via Bayesian information criterion. Real-world datasets are evaluated under the proposed model. [ABSTRACT FROM AUTHOR]

PURPOSE: With increased adoption of next-generation sequencing, tailored therapy on the basis of molecular status is being delivered for patients with early-stage resectable non–small-cell lung cancer (NSCLC). The purpose of this narrative review was to focus on recent developments of targeted therapies in the adjuvant and neoadjuvant/adjuvant setting for early-stage disease. METHODS: A systematic search of the MEDLINE/PubMed database was performed, focusing on studies published within the past 10 years. Our search queried "early-stage NSCLC (AND) tyrosine kinase inhibitor (TKI; OR) epidermal growth factor receptor (EGFR; OR) anaplastic lymphoma kinase (ALK)" and was limited only to prospective and ongoing studies. RESULTS: Most studies examining the benefit of targeted therapies in early-stage resectable NSCLC have been for EGFR-TKIs in the adjuvant setting. Currently, only one study, the ADAURA trial of adjuvant osimertinib, has demonstrated an overall survival benefit with the use of an EGFR-TKI in the adjuvant setting. Future work to build on the success of the ADAURA trial is focused on determining the optimal duration of targeted therapies and using biomarkers, such as circulating tumor DNA, to risk-stratify patients and guide maintenance targeted therapy duration. CONCLUSION: The results of several ongoing studies are eagerly awaited regarding the use of targeted therapies in the neoadjuvant/adjuvant setting and for more uncommon or rare mutations such as ALK , ROS proto-oncogene 1, rearranged during transfection, mesenchymal-epithelial transition factor, and B-Raf proto-oncogene V600E. The treatment landscape for early-stage NSCLC harboring actionable mutations is likely to shift dramatically in the upcoming decade. [ABSTRACT FROM AUTHOR]

Background: Molecular testing (MT) is emerging as a potential prognostic factor that can be available before treatment of differentiated thyroid carcinoma begins. Among patients eligible for either lobectomy or total thyroidectomy as their initial therapy, our study aims were to assess (1) if conventionally available preoperative factors are associated with incomplete response to initial therapy, and (2) if MT results can be a surrogate for the ATA Risk Stratification System (RSS) to estimate risk of recurrence. Methods: The data of consecutive thyroid cancer patients without preoperative lateral neck disease or distant metastasis who underwent index thyroidectomy between November 1, 2017 and October 31, 2021 were reviewed. Logistic regression models including preoperative variables such as MT and/or the postoperatively available RSS were constructed to predict disease recurrence, either structural or biochemical. Model discrimination using the c-statistic and goodness-of-fit test were compared. Results: Among 945 patients studied, 50 (5.2%) recurred with 18-month median follow-up. Recurrences were detected in 17 (2.9%), 20 (6.7%), and 13 (22.8%) patients with RSS-low, -intermediate, and -high cancers, respectively (p < 0.001). In multivariable analysis, only tumor size was associated with recurrence (odds ratio [OR] 1.3, 95% confidence interval [CI] 1.1–1.5). In a different model analyzing 440 (46.6%) patients with available MT results, recurrence was associated with both larger tumor size (OR 1.4 [95% CI 1.1–1.8]) and MT results (p < 0.001). Including MT improved the c-statistic by 27%, which was statistically no different than the model incorporating only the RSS (p = 0.15). Conclusions: Disease recurrence was observed across all ATA RSS categories in short-term follow-up, and tumor size was the only conventional preoperative factor associated with recurrence. When MT results were incorporated, they not only improved predictive ability beyond tumor size alone, but also yielded similar ability as the gold standard ATA RSS. Thus, MT results might aid the development of novel preoperative risk stratification algorithms. [ABSTRACT FROM AUTHOR]

This study aims to explore how personal ties and organizational ties between a distributor and its manufacturer influence the altruistic extra-role behavior of the focal distributor and the mediating effect of organizational learning, as well as the moderating effect of environmental dynamism, on the relationship between interfirm relationships and organizational learning. The authors collect data from 618 household appliance distributors from Mainland China to support most hypotheses. The multilevel regression analysis and bootstrap test are used to test the hypotheses. Both personal ties and organizational ties positively affect distributor organizational learning. Environmental dynamism strengthens the positive relationship between organizational ties and distributor organizational learning; distributor organizational learning plays a mediating role in the positive relationship between interfirm and altruistic extra-role behavior. At the same time, the mediating effect of distributor organizational learning between interfirm relationships and altruistic extra-role behavior becomes stronger with the increase of environmental dynamism. This study integrates the concept of organizational learning into the framework of research on the relationship between inter-firm relationships and extra-role altruistic behavior. In the background of a global epidemic, the concept of environmental dynamics is used as a boundary effect to deepen our understanding of relationships. The study also offers suggestions on how managers consider inter-firm relationships and extra-role altruistic behavior. This study explores organizational learning as an intermediary mechanism between interfirm relationships and altruistic extra-role behavior, enriching the literature on altruistic extra-role behavior. It uncovers the boundary effect of environmental dynamics to deepen our understanding of the effect of interfirm relationships on organizational learning. It also discusses the antecedents of altruistic extra-role behavior by integrating previous studies and considering the impact of the two types of interfirm relationships simultaneously. This study provides several insightful implications for the managers in understanding the impacts of interfirm relationships on altruistic extra-role behavior in business-to-business marketing. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to improve the understanding of the interrelationships between sociodemographic factors, pregnancy intention, and antenatal care by: (1) identifying sociodemographic predictors of unintended pregnancy; (2) examining associations between unintended pregnancy types and antenatal care (ANC) inadequacy; (3) examining how the association between unintended pregnancy and ANC inadequacy is modified by maternal characteristics; and (4) identifying sociodemographic predictors of ANC inadequacy by pregnancy intention status. Methods: We analyzed women 15–49 years of age who participated in the nationwide cross-sectional Vietnam Multiple Indicator Cluster Survey. Pregnancy intention and ANC adequacy were assessed for the most recent live birth within two years preceding survey completion. Weighted Poisson regression was used to estimate risk ratios. Results: Of the 1,474 study participants, 17.8% had unintended pregnancy and 29.0% had inadequate ANC. There was no significant confounding-adjusted association between unintended pregnancy and ANC inadequacy, except in those currently not working. Women with intended pregnancy or unintended pregnancy had significantly higher ANC inadequacy risk if they lived in rural areas, were less educated, and had no media exposure, lower wealth status, or more than two children. Younger age, ever given birth, having child loss, and positive attitude towards partner violence were significant predictors of ANC inadequacy only in women with intended pregnancy. Conclusions for Practice: ANC inadequacy was more strongly predicted by sociodemographic characteristics rather than pregnancy intention, and the sociodemographic variables' prediction of ANC inadequacy was stronger in women with intended pregnancy than unintended pregnancy. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic cancers are highly aggressive tumors that carry a poor prognosis. With recent advances in radiation therapy techniques and systemic therapy, there is hope that the treatment landscape for pancreatic cancers will improve in the near future. This review summarizes radiation dose escalation strategies to improve outcomes in locally advanced pancreatic cancer as well as novel neoadjuvant therapy strategies to improve outcomes in resectable and borderline resectable pancreatic cancers. This review aims to summarize the recent advances in radiation oncology for pancreatic cancer. A systematic search of the MEDLINE/PubMed database and Clinicaltrials.gov was performed, focusing on studies published within the last 10 years. Our search queried "locally advanced pancreatic cancer [AND] stereotactic body radiation therapy (SBRT) [OR] hypofractionation [OR] magnetic resonance guidance radiation therapy (MRgRT) [OR] proton" and "borderline resectable pancreatic cancer [AND] neoadjuvant radiation" and was limited only to prospective and retrospective studies and metanalyses. For locally advanced pancreatic cancers (LAPC), retrospective evidence supports the notion of radiation dose escalation to improve overall survival (OS). Novel methods for increasing the dose to high risk areas while avoiding dose to organs at risk (OARs) include SBRT or ablative hypofractionation using a simultaneous integrated boost (SIB) technique, MRgRT, or charged particle therapy. The use of molecularly targeted agents with radiation to improve radiosensitization has also shown promise in several prospective studies. For resectable and borderline resectable pancreatic cancers (RPC and BRPC), several randomized trials are currently underway to study whether current neoadjuvant regimens using radiation may be improved with the use of the multi-drug regimen FOLFIRINOX or immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

This article focuses on the design of proportional‐derivative (PD) controllers for positive linear systems in the continuous‐time domain, which is a well‐known open problem in positive systems theory. The main objective is to design a PD controller subject to interval gain variations, which simultaneously preserves the closed‐loop system stability and positivity. The provided results fill the literature gap by considering both the PD controller structure and positivity. Although various feedback control strategies of positive systems have been developed recently, the work provides, for the first time, a systematic and tractable framework for finding nonfragile PD controller gains for positive stabilization. Finally, the theory and algorithm performance are evaluated and illustrated by numerical examples. [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]

Background: Internal mammary artery pseudoaneurysms most commonly develop from thoracic penetrating trauma or procedures. However, other important etiologies should not be overlooked. Case Report: A 27-year-old female presentedwith antiphospholipid antibody syndrome, thrombotic microangiopathy, end-stage renal disease on hemodialysis, and epilepsy. On admission, the patient had pulseless electrical activity and hypertensive emergency. After the patientwas successfully resuscitated, she developed status epilepticus. Laboratoryworkup on admission revealed a subtherapeutic international normalized ratio, elevated C-reactive protein and sedimentation rate, and acute anemia. Imaging showed a right-sided subdural hematoma with amidline shift and likely internal mammary artery pseudoaneurysm. Angiography demonstrated aneurysmal dilation, segmental narrowing, and a string of beads appearance. Because of our patient's demographics, string of beads appearance on diagnostic angiography, history of renal disease, and negative hepatitis serology, fibromuscular dysplasia was considered the etiology of the internal mammary artery pseudoaneurysm. The family opted for 2 burr holes and a subdural drain but declined further diagnostic and therapeutic interventions because of anoxic brain injury and poor prognosis. Conclusion: In this patient, the etiology of the internal mammary artery pseudoaneurysm was attributed to fibromuscular dysplasia. Although this patient's family chose comfortmeasures, treatmentmethods are available for internal mammary artery pseudoaneurysms. [ABSTRACT FROM AUTHOR]

Coeliac disease (CD) is a chronic immune‐mediated enteropathy triggered by ingestion of gluten. The aim of this study was to investigate if the salivary glands as a component of the mucosal immune system are involved in CD, leading to sialadenitis and salivary gland dysfunction and associated oral manifestations. Twenty patients with CD aged 49.2 (SD 15.5 years) and 20 age‐ and gender‐matched healthy controls underwent an interview regarding general and oral health, serological analysis, a clinical oral examination including bitewing radiographs, Candida smear, assessment of salivary mutans streptococci and lactobacilli levels, unstimulated and chewing‐stimulated whole and parotid saliva flow rates, analysis of secretory IgA, and a labial salivary gland biopsy. Xerostomia, mucosal lesions, dry/cracked lips and focal lymphocytic sialadenitis were more prevalent and extensive in patients with CD than in healthy controls. Moreover, the patients had less gingival inflammation and higher whole saliva flow rates than the healthy controls, but did not differ regarding dental health and levels of cariogenic bacteria and Candida. The major salivary gland function appears unaffected, contributing to maintenance of a balanced microbiota and oral health in CD patients. Xerostomia and labial dryness may be related to minor salivary gland inflammation and subsequent impaired mucosal lubrication. [ABSTRACT FROM AUTHOR]

In this paper, we explore the stabilization problem of discrete-time Markov jump linear systems from a new perspective. We establish a novel learning-based framework that combines control theory and learning methods to design stabilizing feedback gains. Firstly, we reformulate the stabilization problems for discrete-time Markov jump linear systems into finite-time counterparts. Subsequently, leveraging techniques from the field of learning, we effectively and efficiently solve the finite-time stabilization problems. We systematically investigate two typical stabilization problems of discrete-time Markov jump linear systems within the proposed framework, namely the detector-based feedback stabilization and the static output feedback stabilization problems. Extensive simulation on various numerical examples demonstrates the advantages of our approach over several existing methods for discrete-time Markov jump linear systems. [ABSTRACT FROM AUTHOR]

Background: The common dermatologie manifestations seen in patients with coronavirus disease 2019 (COVID-19) include morbilliform, pernio-like, urticarial, macular erythematous, vesicular, and papulosquamous disorders, as well as retiform purpura. Although cases of acro-ischemia have been demonstrated, they are not well studied or reported. Case Report: A 73-year-old male was admitted for acute hypoxic respiratory failure secondary to COVID-19 infection. During the patient's hospital course, his oxygen requirement progressively increased, and he developed painful, violaceous purpura on his right lower extremity digits. The patient was treated with therapeutic doses of enoxaparin and nitroglycerin ointment in the hospital and apixaban on discharge. The patient was lost to follow-up. Conclusion: The multiorgan dysfunction associated with COVID-19 includes dermatologic manifestations. This case illustrates that acro-ischemia can resolve with guideline-based medical treatment. [ABSTRACT FROM AUTHOR]

Hybrid species tend to exhibit a mixture of parent characteristics; we propose chimeral clusters as exhibiting a mixture of parent parameters, a type of intercluster structure. Morphometric measurements in the iris dataset describe the hybrid Iris versicolor as intermediate to those of parent species Iris setosa and Iris virginica, which motivates our extension of Gaussian mixture models to allow mixing in the parameter space. We propose a mixing mechanism whereby chimeral clusters are parameterized by a convex combination of fully varying prototype cluster parameters and characterize the identifiability of the postulated mixture model. Estimation of chimeral clustering models is described using variations of the expectation-maximization algorithm and the solution to the continuous-time algebraic Riccati equation. The efficacy of chimeral clustering is demonstrated using morphometric datasets describing iris, Cooper's hawks, and water striders, with comparisons to typical Gaussian mixture models. We evaluate parameter recovery on a synthetic dataset and demonstrate that parsimonious covariance matrices and chimeral clustering capture different kinds of intercluster structure. [ABSTRACT FROM AUTHOR]

Aim and objectives: To explore and understand the current practice, perceptions, and knowledge of general surgery trainees, advanced practice providers, and surgical nurses regarding opioid prescribing and administration. To this end, a novel opioid education and training was introduced to educate these practitioners on safe opioid practices in surgical patients. Background: National awareness of the opioid epidemic has increased significantly in the last several years. However, there remain a disturbingly high number of opioid prescriptions written in the US indicating a need for improved provider and nurse education. This involves increasing awareness and understanding of national guidelines as well as implementing multi‐modal therapy to treat pain. Design: Pre–post‐intervention quality improvement project. Methods: An opioid education and training involving a morphine equivalent daily dosing calculator in the electronic medical record was provided to 26 surgical trainees, eight advanced practice providers and 97 surgical nurses in November 2019. Perceptions, current practice and knowledge were measured using a pre‐ and post‐intervention survey (SQUIRE checklist). Results: The survey results showed a positive clinical change in perception of opioid use in surgical patients following the intervention and a modest decrease in the average morphine equivalent daily dosing at discharge in general and transplant surgery patients. Conclusions: Effective pain management for surgical patients must be individualised. Safe opioid prescribing should involve an interdisciplinary approach with all members of the team undergoing assessment of their opioid knowledge and prescribing habits, easily accessible training tools and opioid calculators in the electronic medical record. Relevance to Clinical Practice: Our initiative may provide useful information to settings that replicate use of a morphine equivalent daily dosing calculator in the electronic medical record. Utilisation of safe opioid prescribing tools in the electronic medical record and continuing education for providers and nurses can help ensure the safety of surgical patients. [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]

We solve the convergence case of the generalized Baker–Schmidt problem for simultaneous approximation on affine subspaces, under natural diophantine type conditions. In one of our theorems, we do not require monotonicity on the approximation function. In order to prove these results, we establish asymptotic formulae for the number of rational points close to an affine subspace. One key ingredient is a sharp upper bound on a certain sum of reciprocals of fractional parts associated with the matrix defining the affine subspace. [ABSTRACT FROM AUTHOR]

Introduction: Cancer patients are increasingly incorporating medical marijuana into the management of treatment-related side effects. Currently however, data is limited regarding the risks and benefits of therapeutic cannabis for cancer patients. We sought to characterize radiation oncologists' practices and opinions regarding therapeutic cannabis via a nationwide survey. Materials and methods: An anonymous survey was distributed via email to 873 radiation oncologists in the American Society for Radiation Oncology member database. Radiation oncologists were asked their opinions and practices regarding the use of therapeutic cannabis for their patients. Bivariate analyses of potential predictors for responses were conducted using standard statistical techniques. Results: One hundred seven radiation oncologists completed the survey. According to the survey, 36% of respondents would recommend therapeutic cannabis to their patients to mitigate treatment toxicity. Physicians practicing in states where medical marijuana is legal were more likely to recommend it compared to physicians working in states that have not legalized medical marijuana (OR = 3.79, 1.19–12.1, p = 0.01). Seventy-one percent of respondents reported therapeutic cannabis as being effective at least some of the time for managing treatment-related toxicities. Fifty-eight percent of physicians reported lacking sufficient knowledge to advise patients regarding therapeutic cannabis, while 86% of respondents were interested in learning more about therapeutic cannabis for cancer patients. Conclusions: Although a majority of radiation oncologists believe there are benefits to therapeutic cannabis, many are hesitant to recommend for or against its use. Radiation oncologists appear to be interested in learning more about how therapeutic cannabis may play a role in their patients' care. [ABSTRACT FROM AUTHOR]

This article considers the problem of designing lead, lag, and lead-lag compensators for multi-input–multi-output (MIMO) linear systems under the $H_{\infty }$ performance measure. This is the first time that the lead, lag and lead-lag compensators are generalized to the MIMO cases by preserving their classical compensator structures. Theoretical results on the stability analysis and synthesis of MIMO systems under the $H_{\infty }$ control performance with the proposed lead, lag, and lead-lag compensators are obtained. Then relevant algorithms for designing lead, lag, and lead-lag compensators are provided to determine the compensator parameters. Differing from traditional design methods, which mostly rely on some trial-and-error procedures, the proposed methods are algorithmic and the compensators can be synthesized systematically. Illustrative examples are used to demonstrate the effectiveness and advantages of the proposed methods. [ABSTRACT FROM AUTHOR]

This article addresses the real‐time reachable set problem on nonlinear time‐delay switched singular systems with state jump, which is subject to initial state and peak‐bound disturbance. Initially, based on the system state decomposition method, a state jump lemma is proposed, which combines the nonlinear function and the system state at the switching instant. Then, a real‐time bounded lemma is developed, premised on using the idea of average dwell‐time and analyzing subinterval function changes. Afterwards, the sufficient conditions for estimating the real‐time and nonreal‐time reachable set are established, which ensures that the reachable state of system can be restricted within a real‐time or nonreal‐time closed set. Finally, simulation results of the typical Direct Current boost chopper are performed to exhibit the effectiveness of the devised estimation scheme for the real‐time reachable set of system. [ABSTRACT FROM AUTHOR]

Summary: This paper addresses the problem of switching control for systems subject to external disturbances that vary over multiple frequency ranges. Specifically, two different scenarios of disturbance injection are considered; namely, the disturbance may switch between different prescribed frequency ranges, subject to an average dwell time setting, or the disturbance may reside within one of the frequency ranges. To address these scenarios, a disturbance‐triggered control scheme is developed that divides the entire frequency range into low‐, mid‐, and high‐frequency ranges. This scheme ensures closed‐loop stability under average dwell time frequency‐range switching and achieves H∞$$ {H}_{\infty } $$ performance when operated under individual frequency ranges. Synthesis conditions in matrix inequalities are derived to characterize the switching control, and an iterative algorithm is proposed for finding a desired set of controller gains. Finally, two examples are presented to illustrate the effectiveness of the proposed control method. [ABSTRACT FROM AUTHOR]

The development of mobile-health technology has the potential to revolutionize personalized medicine. Biomedical sensors (e.g. wearables) can assist with determining treatment plans for individuals, provide quantitative information to healthcare providers, and give objective measurements of health, leading to the goal of precise phenotypic correlates for genotypes. Even though treatments and interventions are becoming more specific and datasets more abundant, measuring the causal impact of health interventions requires careful considerations of complex covariate structures, as well as knowledge of the temporal and spatial properties of the data. Thus, interpreting biomedical sensor data needs to make use of specialized statistical models. Here, we show how the Bayesian structural time series framework, widely used in economics, can be applied to these data. This framework corrects for covariates to provide accurate assessments of the significance of interventions. Furthermore, it allows for a time-dependent confidence interval of impact, which is useful for considering individualized assessments of intervention efficacy. We provide a customized biomedical adaptor tool, MhealthCI, around a specific implementation of the Bayesian structural time series framework that uniformly processes, prepares, and registers diverse biomedical data. We apply the software implementation of MhealthCI to a structured set of examples in biomedicine to showcase the ability of the framework to evaluate interventions with varying levels of data richness and covariate complexity and also compare the performance to other models. Specifically, we show how the framework is able to evaluate an exercise intervention's effect on stabilizing blood glucose in a diabetes dataset. We also provide a future-anticipating illustration from a behavioral dataset showcasing how the framework integrates complex spatial covariates. Overall, we show the robustness of the Bayesian structural time series framework when applied to biomedical sensor data, highlighting its increasing value for current and future datasets. Author summary: In this paper, we propose and describe a robust and flexible modelling framework called MhealthCI based on the Bayesian structural time series, for which we have found to excel at analyzing diverse biosensor data. While Bayesian modelling is often employed in various fields such as finance, marketing, and weather forecasting, it is rarely used in biomedicine, specifically for biosensor and wearable data relating to human health and behavior. We use and apply this framework with the goal of interpreting and quantifying the causal impact of an intervention, a widespread goal of biomedicine. We describe the diversity of data types to which it could apply, provide intuition to its mechanics, collect relevant data in various fields, provide a wrapper tool around well-known R packages that prepares and registers diverse biosensor data to be analyzed, and finally apply the method to showcase its strength in quantifying the impact of interventions. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Among survivors from first primary cancers that occurred during childhood and adolescence, their risks of developing subsequent primary digestive system cancers are not well understood. Therefore, we conducted the largest and most comprehensive analysis examining risks for diverse types of digestive system cancers after survival from a wide variety of first primary childhood and adolescent cancers. METHODS: We identified 41,249 patients diagnosed with first primary cancer from 1975 to 2015 before 20 years of age from 9 Surveillance, Epidemiology and End Results Program registries. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) for digestive system cancers were calculated controlling for age, sex, race, and calendar year. RESULTS: Among 41,249 cancer survivors, 133 developed subsequent primary digestive system cancer, with a median digestive system cancer diagnosis age of 37 years. The SIR and AER for any digestive system cancer were highest among survivors of bone cancer, lymphoma, and neuroblastoma. Among survivors from any first primary cancer, the SIR was significantly elevated for cancer of the esophagus, stomach, small intestine, large intestine, liver, and pancreas, whereas the AER was highest for large intestine cancer. DISCUSSION: Childhood and adolescent cancer survivors diagnosed from 1975 to 2015 have significantly elevated risks of digestive system cancers compared with the US general population. Our detailed findings may contribute to surveillance recommendations of childhood and adolescent cancer survivors and promote future studies to further understand mechanisms by which having various first primary cancers lead to subsequent primary digestive system cancers. [ABSTRACT FROM AUTHOR]

Summary: This article investigates the consensus problem for positive multiagent systems via an observer‐based dynamic output‐feedback protocol. The dynamics of the agents are modeled by linear positive systems and the communication topology of the agents is expressed by an undirected connected graph. For the consensus problem, the nominal case is studied under the semidefinite programming framework while the robust and nonfragile cases are investigated under the linear programming framework. It is required that the distributed state‐feedback controller and observer gains should be structured to preserve the positivity of multiagent systems. Necessary and/or sufficient conditions for the analysis of consensus are obtained by using positive systems theory and graph theory. For the nominal case, necessary and sufficient conditions for the codesign of state‐feedback controller and observer of consensus are derived in terms of matrix inequalities. Sufficient conditions for the robust and nonfragile consensus designs are derived and the codesign of state‐feedback controller and observer can be obtained in terms of solving a set of linear programs. Numerical simulations are provided to show the effectiveness and applicability of the theoretical results and algorithms. [ABSTRACT FROM AUTHOR]

Background: During transcription, numerous transcription factors (TFs) bind to targets in a highly coordinated manner to control the gene expression. Alterations in groups of TF-binding profiles (i.e. "co-binding changes") can affect the co-regulating associations between TFs (i.e. "rewiring the co-regulator network"). This, in turn, can potentially drive downstream expression changes, phenotypic variation, and even disease. However, quantification of co-regulatory network rewiring has not been comprehensively studied. Results: To address this, we propose DiNeR, a computational method to directly construct a differential TF co-regulation network from paired disease-to-normal ChIP-seq data. Specifically, DiNeR uses a graphical model to capture the gained and lost edges in the co-regulation network. Then, it adopts a stability-based, sparsity-tuning criterion -- by sub-sampling the complete binding profiles to remove spurious edges -- to report only significant co-regulation alterations. Finally, DiNeR highlights hubs in the resultant differential network as key TFs associated with disease. We assembled genome-wide binding profiles of 104 TFs in the K562 and GM12878 cell lines, which loosely model the transition between normal and cancerous states in chronic myeloid leukemia (CML). In total, we identified 351 significantly altered TF co-regulation pairs. In particular, we found that the co-binding of the tumor suppressor BRCA1 and RNA polymerase II, a well-known transcriptional pair in healthy cells, was disrupted in tumors. Thus, DiNeR successfully extracted hub regulators and discovered well-known risk genes. Conclusions: Our method DiNeR makes it possible to quantify changes in co-regulatory networks and identify alterations to TF co-binding patterns, highlighting key disease regulators. Our method DiNeR makes it possible to quantify changes in co-regulatory networks and identify alterations to TF co-binding patterns, highlighting key disease regulators. [ABSTRACT FROM AUTHOR]

Endoscopic biliary stenting (EBS) and percutaneous transhepatic biliary drainage (PTBD) are two techniques used for preoperative biliary drainage prior to hepatobiliary resection. The objectives of this study were to determine predictors of the drainage technique selection and to evaluate the association between drainage technique and postoperative outcomes. Using ACS NSQIP data (2014–2017), patients who underwent preoperative biliary drainage prior to hepatobiliary resection for malignancy were identified. Separate multivariable-adjusted, propensity score (PS) adjusted, and PS matched logistic regression models were constructed to evaluate the association between drainage technique and postoperative outcomes. Of 527 patients identified, 431 (81.8%) received EBS and 96 (18.2%) received PTBD. Patients who underwent PTBD had more preoperative co-morbidities, including higher ASA class, recent weight loss, and hypoalbuminemia (all p < 0.05). After multivariable adjustment, PTBD was significantly associated with 30-day DSM (OR 1.92, 95% CI 1.24–2.97, p = 0.004), overall SSI (OR 1.74, 95% CI 1.10–2.76, p = 0.019), and superficial SSI (OR 2.08, 95% CI 1.20–3.60, p = 0.010). These findings remained significant for both PS-adjusted and PS-matched models. Patients undergoing hepatobiliary resection selected for PTBD had significantly more preoperative co-morbidities and nutritional deficits. Compared to EBS, PTBD was associated with significantly higher odds of postoperative morbidity and mortality. [ABSTRACT FROM AUTHOR]

This paper studies the issue of finite-time time-varying output-feedback control for positive time-varying discrete-time linear systems. Finite-time stability for the systems with positivity is defined. To make sure that the system can be finite-time stable with positivity, an analysis condition is established first, and then two conditions for solving the static output-feedback controller are derived in this work where all the obtained results are necessary and sufficient conditions. An iterative algorithm for solving the controller is developed and finally, an example is given in the simulation to verify the effectiveness of our results and algorithm. [ABSTRACT FROM AUTHOR]

The association between higher surgical volume and better perioperative outcomes after pancreatectomy has been extensively demonstrated. However, how different notions of experience impact outcomes of surgeons operating within high-quality scenarios remains unclear. Self-reported experience parameters from ACS-NSQIP HPB-Collaborative surgeons were merged with 2014–2016 ACS-NSQIP clinical data. The association of various experience parameters with outcomes was investigated through uni- and multivariable analyses. Hierarchical regression assessed surgeon performance. 111/151 HPB-Collaborative surgeons provided responses (73.5%). Compared to the other 532 ACS-NSQIP surgeons performing pancreatectomy, HPB-Collaborative surgeons performed 7692/16,239 of the overall pancreatectomies (47.3%), with improved outcomes of serious morbidity, pancreatic fistula, reoperation, duration of stay and readmissions. Median age of respondents was 49 years and 92.8% were fellowship-trained. Median career and annual pancreatectomy volume were 400 and 35, respectively; median annual institutional volume was 100 resections. On unadjusted analyses, several aspects of experience were associated with the outcomes studied, especially for pancreatoduodenectomy; however, none remained significant after multivariable adjustment. Surgeons' profiling showed substantial homogeneity in performance for both pancreatoduodenectomy and distal pancreatectomy. Contemporary data shows that for surgeons operating in high quality settings clinical outcomes are largely independent of indicators of greater experience. [ABSTRACT FROM AUTHOR]

Background: Assessments of surgical quality should consider both surgeon and patient perspectives simultaneously. Focusing on patients undergoing major gastrointestinal cancer surgery, we sought to characterize hospitals, and their patients, on both these axes of quality.Methods: Using the American College of Surgeons' National Surgical Quality Improvement Program registry, hospitals were profiled on a risk-adjusted composite measure of death or serious morbidity (DSM) generated from patients who underwent colectomy, esophagectomy, hepatectomy, pancreatectomy, or proctectomy for cancer between January 1, 2015 and December 31, 2016. These hospitals were also profiled using the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey. Highest-performing hospitals on both quality axes, and their respective patients, were compared to the lowest-performing hospitals.Results: Overall, 60,526 patients underwent their cancer operation at 530 hospitals. There were 38 highest- and 48 lowest-performing hospitals. The correlation between quality axes was poor (ρ = 0.10). Compared to the lowest-performing hospitals, the highest-performing hospitals were more often NCI-designated cancer centers (29.0% vs. 4.2%, p = 0.002) and cared for a lower proportion of Medicaid patients (0.14 vs. 0.23, p < 0.001). Patients who had their operations at the lowest- versus highest-performing hospitals were more often black (17.2% vs. 8.4%, p < 0.001), Hispanic (8.3% vs. 3.5%, p < 0.001), functionally dependent (3.8% vs. 0.9%, p < 0.001), and not admitted from home (4.4% vs. 2.4%, p < 0.001).Conclusions: Hospital performance varied when assessed by both risk-adjusted surgical outcomes and patient experiences. In this study, poor-performing hospitals appeared to be disproportionately serving disadvantaged and minority cancer patients. [ABSTRACT FROM AUTHOR]

Abstract Background Whether the choice of antibiotic prophylaxis, the type of incision, or the use of wound protectors decreases surgical site infections (SSIs) in patients undergoing pancreatoduodenectomy (PD) remains unknown. Methods Patients undergoing open, elective PD between January 1, 2016 and June 30, 2017 were identified from the American College of Surgeons' National Surgical Quality Improvement Program registry. Multivariable logistic regression models were constructed to determine the association of antibiotic prophylaxis type, incision type, and wound protector use on the incidence of any, superficial, and organ/space SSIs, and to profile hospitals. Results Overall, 5969 patients were included from 140 hospitals. The overall rate of SSI was 20.3% (n = 1213). Superficial SSIs occurred in 432 (7.2%) patients and organ/space SSIs in 841 (14.1%). Wound protector use was associated with 23% lower odds of experiencing any SSIs (OR 0.77, 95% CI 0.60–0.98), reflective of the decreased odds associated with superficial SSIs (OR 0.65, 95% CI 0.44–0.97), but not organ/space SSIs (OR 0.89, 95% CI 0.68–1.17). Highest-performing hospitals frequently utilized broad-spectrum antibiotics, midline incisions, and wound protectors. Conclusion Wound protectors reduced superficial, but not organ/space, infections in patients undergoing pancreatoduodenectomy. Routine use of wound protectors in patients undergoing proximal pancreatectomy is recommended. [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]

Two experiments were conducted with growing and finishing swine to determine the effect of phytase supplementation of sorghum-canola meal diets without added inorganic phosphorus ( iP ) on growth performance, apparent total-tract P, calcium ( Ca ), nitrogen ( N ), and energy utilization, bone strength, bone ash, serum Ca and P concentrations, and serum phosphatase activity. For Exp. 1, 42 crossbred barrows in individual metabolism cages were fed a P-deficient diet for 7 d before starting a 28-d experiment at 24.8 kg body weight ( BW ). Experiment 1 had 7 treatments that were a negative control ( NC ) diet supplemented with 0, 400, 800, 1200, or 1600 U of Aspergillus niger ( AN ) phytase / kg, a positive control ( PC ) diet, and the PC diet supplemented with 1200 U of AN phytase / kg. Fecal and urine collections were made from d 21–26. Blood samples were collected on d 0, 14, and 28. For Exp. 2, 126 growing-finishing crossbred swine with an initial BW of 21.6 kg were group-fed (3 pigs/pen) in 3 phases (grower, early-finisher, and late-finisher). Experiment 2 had 6 treatments that were a NC diet for each phase supplemented with 0, 200, 400, 600, or 800 U of AN phytase / kg and a PC diet. Fecal collections were made from d 49–54. Blood samples were collected on d 35, 63, and 91. For both experiments, 400 U of AN phytase / kg of diet was adequate ( P  ≤ 0.05) for growth performance compared with the PC treatment groups. For Exp. 1, apparent total-tract P absorption and retention plateaued at 1200 U of AN phytase / kg of diet ( P  < 0.01), with fecal Ca and P excretion reduced 22.4% and 28.6%, respectively, compared with the PC treatment group. However, pigs fed the PC + 1200 U of AN phytase / kg absorbed and retained more P (g / d, P  < 0.01) than any other treatment group. For Exp. 2, apparent total-tract P absorption, bone strength, and bone ash weight plateaued at 600 U of AN phytase / kg of diet ( P  < 0.01), with fecal P excretion reduced 29.4% compared with the PC treatment group. For both experiments, the AN phytase treatments did not increase Ca, N, or energy absorption (amount / d or % of intake), and had no effect on serum Ca and P concentrations, or the serum activity of alkaline phosphatase, total acid phosphatase, or tartrate-resistant acid phosphatase. [ABSTRACT FROM AUTHOR]

Background: Current preoperative cardiac risk stratification practices group operations into broad categories, which might inadequately consider the intrinsic cardiac risks of individual operations. We sought to define the intrinsic cardiac risks of individual operations and to demonstrate how grouping operations might lead to imprecise estimates of perioperative cardiac risk.Methods: Elective operations (based on Common Procedural Terminology codes) performed from January 1, 2010 to December 31, 2015 at hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program were studied. A composite measure of perioperative adverse cardiac events was defined as either cardiac arrest requiring cardiopulmonary resuscitation or acute myocardial infarction. Operations' intrinsic cardiac risks were derived from mixed-effects models while controlling for patient mix. Resultant risks were sorted into low-, intermediate-, and high-risk categories, and the most commonly performed operations within each category were identified. Intrinsic operative risks were also examined using a representative grouping of operations to portray within-group variation.Results: Sixty-six low, 30 intermediate, and 106 high intrinsic cardiac risk operations were identified. Excisional breast biopsy had the lowest intrinsic cardiac risk (overall rate, 0.01%; odds ratio, 0.11; 95% CI, 0.02 to 0.25) relative to the average, whereas aorto-bifemoral bypass grafting had the highest (overall rate, 4.1%; odds ratio, 6.61; 95% CI, 5.54 to 7.90). There was wide variation in the intrinsic cardiac risks of operations within the representative grouping (median odds ratio, 1.40; interquartile range, 0.88 to 2.17).Conclusions: A continuum of intrinsic cardiac risk exists among operations. Grouping operations into broad categories inadequately accounts for the intrinsic cardiac risk of individual operations. [ABSTRACT FROM AUTHOR]

Hypocalcemia following total thyroidectomy (TT) is common due to postoperative parathyroid dysfunction and vitamin D deficiency. Given the association between obesity and vitamin D deficiency, we sought to correlate body mass index (BMI) with hypocalcemia after TT. Patients undergoing TT between 2016 and 2020 were identified from the American College of Surgeons National Surgical Quality Improvement Program thyroidectomy-targeted database. Univariable and multivariable regressions, stratified by BMI category (normal, overweight, obese), identified factors associated with hypocalcemia prior to discharge, within 30 d, and severe hypocalcemic events (emergent evaluation, intravenous calcium supplementation, or readmission). Sixteen thousand two hundred seventy seven TT were performed with available BMI data. Three thousand five hundred thirty one (21.7%) patients had normal BMI, 4823 (29.6%) were overweight, and 7772 (47.7%) were obese. Patients with BMI ≥ 25 had decreased risk of hypocalcemia before discharge (9.8% versus 13%, odds ratio [OR] 0.73, P < 0.001), 30 d (8.1% versus 10.4%, OR 0.76, P < 0.001), and severe hypocalcemic events (5.5% versus 6.4%, OR 0.84, P = 0.029) compared to normal BMI patients. On multivariable analysis for normal BMI patients, age < 45 y was a risk factor for hypocalcemia before discharge, 30 d, and severe hypocalcemic events (P < 0.05 for all). Additional risk factors in this group for 30-d hypocalcemia included parathyroid autotransplant and central neck dissection (P < 0.05) and recurrent laryngeal nerve injury for severe hypocalcemic events (P = 0.01). Younger patients with BMI < 25 are at an increased risk for hypocalcemia and severe hypocalcemic events after TT. These patients may benefit from preoperative counseling and increased calcium/vitamin D supplementation to reduce prolonged hospitalization and mitigate morbidity. [ABSTRACT FROM AUTHOR]

There is currently no clear distinction between the treatment of HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma (OPSCC). HPV-positive OPSCC has been demonstrated to be more radiosensitive than its HPV-negative counterpart. Despite this, patients with HPV-positive OPSCC continue to receive a full dose of radiation (70 Gy) outside clinical trials. However, this high dose comes with considerable morbidities, including severe mucositis, dysphagia, and xerostomia. We describe the cases of 2 patients with HPV-positive OPSCC who received two cycles of high-dose cisplatin at 100 mg/m2 on 3 separate days, along with concurrent radiotherapy at 50 Gy in 25 fractions for one and 46 Gy in 23 fractions for the other. During treatment, both patients experienced significant acute-phase toxicities—including grade 3 mucositis, grade 3 nausea, and grade 2 dermatitis—and their treatment regimen was stopped before its planned completion. Nevertheless, after a follow-up of 75 and 78 months, respectively, neither patient exhibited any evidence of disease. Late toxicities included grade 1 xerostomia, grade 1 pharyngeal-phase dysphagia, and grade 1 dysgeusia with some foods. We conclude that de-escalating the dose of radiation for HPV-positive patients by 30% and identifying which patients can safely be treated with this level of dose reduction warrants further study. [ABSTRACT FROM AUTHOR]

Background: Coffee is an important source of antioxidants, and consumption of this beverage is associated with many health conditions and a lower mortality risk. However, no study, to our knowledge, has examined whether varying coffee or caffeine consumption levels are associated with telomere length, a biomarker of aging whose shortening can be accelerated by oxidative stress.Objective: We performed a large comprehensive study on how coffee consumption is associated with telomere length.Methods: We used data from the Nurses' Health Study (NHS), a prospective cohort study of female nurses that began in 1976. We examined the cross-sectional association between coffee consumption and telomere length in 4780 women from the NHS. Coffee consumption information was obtained from validated food-frequency questionnaires, and relative telomere length was measured in peripheral blood leukocytes by the quantitative real-time polymerase chain reaction. Unconditional logistic regression was used to obtain ORs when the telomere length outcome was dichotomized at the median. Linear regression was used for tests of trend with coffee consumption and telomere length as continuous variables.Results: Higher total coffee consumption was significantly associated with longer telomeres after potential confounding adjustment. Compared with non-coffee drinkers, multivariable ORs for those drinking 2 to <3 and ≥3 cups of coffee/d were, respectively, 1.29 (95% CI: 0.99, 1.68) and 1.36 (95% CI: 1.04, 1.78) (P-trend = 0.02). We found a significant linear association between caffeine consumption from all dietary sources and telomere length (P-trend = 0.02) after adjusting for potential confounders, but not after additionally adjusting for total coffee consumption (P-trend = 0.37).Conclusions: We found that higher coffee consumption is associated with longer telomeres among female nurses. Future studies are needed to better understand the influence of coffee consumption on telomeres, which may uncover new knowledge of how coffee consumption affects health and longevity. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does use of perioperative broad-spectrum antibiotics reduce postoperative surgical site infection after open pancreatoduodenectomy? Findings: In this pragmatic, open-label, registry-linked randomized clinical trial including 778 participants from North America, the percentage of patients with 30-day postoperative surgical site infection was statistically significantly reduced with broad-spectrum piperacillin-tazobactam (19.8%) vs standard care cefoxitin (32.8%). Meaning: The findings support the use of piperacillin-tazobactam as perioperative antimicrobial prophylaxis for open pancreatoduodenectomy. Importance: Despite improvements in perioperative mortality, the incidence of postoperative surgical site infection (SSI) remains high after pancreatoduodenectomy. The effect of broad-spectrum antimicrobial surgical prophylaxis in reducing SSI is poorly understood. Objective: To define the effect of broad-spectrum perioperative antimicrobial prophylaxis on postoperative SSI incidence compared with standard care antibiotics. Design, Setting, and Participants: Pragmatic, open-label, multicenter, randomized phase 3 clinical trial at 26 hospitals across the US and Canada. Participants were enrolled between November 2017 and August 2021, with follow-up through December 2021. Adults undergoing open pancreatoduodenectomy for any indication were eligible. Individuals were excluded if they had allergies to study medications, active infections, chronic steroid use, significant kidney dysfunction, or were pregnant or breastfeeding. Participants were block randomized in a 1:1 ratio and stratified by the presence of a preoperative biliary stent. Participants, investigators, and statisticians analyzing trial data were unblinded to treatment assignment. Intervention: The intervention group received piperacillin-tazobactam (3.375 or 4 g intravenously) as perioperative antimicrobial prophylaxis, while the control group received cefoxitin (2 g intravenously; standard care). Main Outcomes and Measures: The primary outcome was development of postoperative SSI within 30 days. Secondary end points included 30-day mortality, development of clinically relevant postoperative pancreatic fistula, and sepsis. All data were collected as part of the American College of Surgeons National Surgical Quality Improvement Program. Results: The trial was terminated at an interim analysis on the basis of a predefined stopping rule. Of 778 participants (378 in the piperacillin-tazobactam group [median age, 66.8 y; 233 {61.6%} men] and 400 in the cefoxitin group [median age, 68.0 y; 223 {55.8%} men]), the percentage with SSI at 30 days was lower in the perioperative piperacillin-tazobactam vs cefoxitin group (19.8% vs 32.8%; absolute difference, −13.0% [95% CI, −19.1% to −6.9%]; P <.001). Participants treated with piperacillin-tazobactam, vs cefoxitin, had lower rates of postoperative sepsis (4.2% vs 7.5%; difference, −3.3% [95% CI, −6.6% to 0.0%]; P =.02) and clinically relevant postoperative pancreatic fistula (12.7% vs 19.0%; difference, −6.3% [95% CI, −11.4% to −1.2%]; P =.03). Mortality rates at 30 days were 1.3% (5/378) among participants treated with piperacillin-tazobactam and 2.5% (10/400) among those receiving cefoxitin (difference, −1.2% [95% CI, −3.1% to 0.7%]; P =.32). Conclusions and Relevance: In participants undergoing open pancreatoduodenectomy, use of piperacillin-tazobactam as perioperative prophylaxis reduced postoperative SSI, pancreatic fistula, and multiple downstream sequelae of SSI. The findings support the use of piperacillin-tazobactam as standard care for open pancreatoduodenectomy. Trial Registration: ClinicalTrials.gov Identifier: NCT03269994 This phase 3 randomized clinical trial examines the effect of broad-spectrum perioperative antimicrobial prophylaxis on postoperative surgical site infection incidence compared with standard care antibiotics (cefoxitin). [ABSTRACT FROM AUTHOR]