Primary Care Patient Interest in Multi-Cancer Early Detection for Cancer Screening.

Multi-cancer early detection (MCED) tests are being developed, but little is known about patient receptivity to their use for cancer screening. The current study assessed patient interest in such testing. Our team conducted a prospective, observational study among primary care patients in a large, urban health system. They were asked to complete a telephone survey that briefly described a new blood test in development to identify multiple types of cancer, but was not currently recommended or covered by insurance. The survey included items to assess respondent background characteristics, perceptions about MCED testing, and interest in having such an MCED test. We also used multivariable analyses to identify factors associated with patient interest in test use. In 2023, we surveyed 159 (32%) of 500 identified patients. Among respondents, 125 (79%) reported a high level of interest in having an MCED test. Interest was not associated with personal background characteristics, but was positively associated with the following expectations: testing would be recommended for cancer screening, be convenient, and be effective in finding early-stage disease (OR = 11.70, 95% CI: 4.02, 34.04, p < 0.001). Research is needed to assess patient interest and actual uptake when detailed information on testing is presented in routine care.

Respiratory Diaphragm Motion-Based Asynchronization and Limitation Evaluation on Chronic Obstructive Pulmonary Disease.

Background: Chronic obstructive pulmonary disease (COPD) typically causes airflow blockage and breathing difficulties, which may result in the abnormal morphology and motion of the lungs or diaphragm. Purpose: This study aims to quantitatively evaluate respiratory diaphragm motion using a thoracic sagittal magnetic resonance imaging (MRI) series, including motion asynchronization and limitations. Method: First, the diaphragm profile is extracted using a deep-learning-based field segmentation approach. Next, by measuring the motion waveforms of each position in the extracted diaphragm profile, obvious differences in the independent respiration cycles, such as the period and peak amplitude, are verified. Finally, focusing on multiple breathing cycles, the similarity and amplitude of the motion waveforms are evaluated using the normalized correlation coefficient (NCC) and absolute amplitude. Results and Contributions: Compared with normal subjects, patients with severe COPD tend to have lower NCC and absolute amplitude values, suggesting motion asynchronization and limitation of their diaphragms. Our proposed diaphragmatic motion evaluation method may assist in the diagnosis and therapeutic planning of COPD.

Adjuvanted Fusion Protein Vaccine Induces Durable Immunity to Onchocerca volvulus in Mice and Non-Human Primates.

Onchocerciasis remains a debilitating neglected tropical disease. Due to the many challenges of current control methods, an effective vaccine against the causative agent Onchocerca volvulus is urgently needed. Mice and cynomolgus macaque non-human primates (NHPs) were immunized with a vaccine consisting of a fusion of two O. volvulus protein antigens, Ov-103 and Ov-RAL-2 (Ov-FUS-1), and three different adjuvants: Advax-CpG, alum, and AlT4. All vaccine formulations induced high antigen-specific IgG titers in both mice and NHPs. Challenging mice with O. volvulus L3 contained within subcutaneous diffusion chambers demonstrated that Ov-FUS-1/Advax-CpG-immunized animals developed protective immunity, durable for at least 11 weeks. Passive transfer of sera, collected at several time points, from both mice and NHPs immunized with Ov-FUS-1/Advax-CpG transferred protection to naïve mice. These results demonstrate that Ov-FUS-1 with the adjuvant Advax-CpG induces durable protective immunity against O. volvulus in mice and NHPs that is mediated by vaccine-induced humoral factors.

Prognostic Nutritional Index (PNI) as a Potential Prognostic Tool for Exacerbation of COPD in Elderly Patients.

Purpose: In COPD, exacerbation of the disorder causes a deterioration in the quality-of-life and worsens respiratory dysfunction, leading to a poor prognosis. In recent years, nutritional indices have been reported as significant prognostic factors in various chronic diseases. However, the relationship between nutritional indicators and prognosis in elderly subjects with COPD has not been investigated. Patients and methods: We enrolled 91 subjects who received COPD assessment tests (CAT), spirometry, blood tests, and multidetector computed tomography (MDCT). We divided the subjects into two groups according to age (<75 years (n=57) and ≥ 75 years (n=34)). The prognostic nutritional index (PNI) was used to assess immune-nutritional status and was calculated as 10 x serum albumin + 0.005 x total lymphocyte count. We then examined the relationship between PNI and clinical parameters, including exacerbation events. Results: There was no significant correlation between the PNI and CAT, the FEV1%pred, or low attenuation volume percentage (LAV%). In the elderly group, there were significant differences between the groups with or without exacerbation in the CAT and PNI (p=0.008, p=0.004, respectively). FEV1%pred, neutrophil-to-lymphocyte ratio (NLR) and LAV% did not differ between the two groups. The analytical model combining CAT and PNI improved the prediction of exacerbations in the elderly subjects (p=0.0068). Conclusion: In elderly subjects with COPD, CAT were associated significantly with the risk of COPD exacerbation, with PNI also a potential predictor. The combined assessment of CAT and PNI may be a useful prognostic tool in subjects with COPD.

Physician Perceptions on Cancer Screening for LGBTQ+ Patients.

The LGBTQ+ community experiences cancer disparities due to increased risk factors and lower screening rates, attributable to health literacy gaps and systemic barriers. We sought to understand the experiences, perceptions, and knowledge base of healthcare providers regarding cancer screening for LGBTQ+ patients. A 20-item IRB-approved survey was distributed to physicians through professional organizations. The survey assessed experiences and education regarding the LGBTQ+ community and perceptions of patient concerns with different cancer screenings on a 5-point Likert scale. Complete responses were collected from 355 providers. Only 100 (28%) reported past LGBTQ+-related training and were more likely to be female (p = 0.020), have under ten years of practice (p = 0.014), or practice family/internal medicine (p < 0.001). Most (85%) recognized that LGBTQ+ subpopulations experience nuanced health issues, but only 46% confidently understood them, and 71% agreed their clinics would benefit from training. Family/internal medicine practitioners affirmed the clinical relevance of patients' sexual orientation (94%; 62% for medical/radiation oncology). Prior training affected belief in the importance of sexual orientation (p < 0.001), confidence in understanding LGBTQ+ health concerns (p < 0.001), and willingness to be listed as "LGBTQ+-friendly" (p = 0.005). Our study suggests that despite a paucity of formal training, most providers acknowledge that LGBTQ+ patients have unique health needs. Respondents had a lack of consensus regarding cancer screenings for lesbian and transgender patients, indicating the need for clearer screening standards for LGBTQ+ subpopulations and educational programs for providers.

Engaging community members in cancer research: an assessment of an NCI-designated cancer center.

PURPOSE: Despite the importance of engaging community members in research, multiple barriers exist. We conducted a mixed-methods evaluation to understand the opportunities and challenges of engaging community members in basic, clinical, translational, and population science research. METHODS: We designed a survey and an interview guide based on the constructs of the Consolidated Framework for Implementation Research. Surveys were distributed electronically to all cancer center investigators and interviews were conducted virtually with a select group of basic, clinical, and population science investigators. Survey data (n = 77) were analyzed across all respondents using frequency counts and mean scores; bivariate analyses examined differences in responses by research program affiliation, gender, race, and faculty rank. Interviews (n = 16) were audio recorded, transcribed verbatim, and analyzed using a reflective thematic approach. RESULTS: There was strong agreement among investigators that "Community engagement in research will help the SKCC address cancer disparities in the catchment area" (M 4.2, SD 0.9) and less agreement with items such as "I know how to find and connect with community members who I can engage in my research" (M 2.5, SD 1.3). Investigators mentioned challenges in communicating complex science to a lay audience but were open to training and workshops to acquire skills needed to integrate community members into their research. CONCLUSION: Cancer centers should develop and promote training and collaborative opportunities for investigators and community members. Overcoming challenges will lead to more patient- and community-centered cancer research in the future.

The impact of preclinical clerkship in general surgery on medical students' attitude to a surgical career.

PURPOSE: With the advent of a new program for postgraduate medical students in 2004, the number of applicants choosing surgical careers in Japan has been declining. We conducted this study to evaluate the impact of preclinical clerkship and how it affects students' attitudes toward a surgical career. METHODS: The subjects of our study were fifth-year medical students who participated in a clinical clerkship in general surgery in our department between April 2021 and March 2022. We conducted pre- and post-preclinical clerkship surveys to assess the perceived image of surgeons and the impact of clerkship on surgical career interest. RESULTS: Among 132 medical students (77 men and 55 women) who rotated through preclinical clerkship in our department, 125 participated in the survey and 66% expressed interest in a surgical career. In the post-clerkship survey, an increased interest in a surgical career was expressed by 79% of the students; notably, including those who initially expressed interest. Approximately 77% of students were satisfied with the practical skill training they received. CONCLUSION: Engaging medical students early in surgical experience through a preclinical clerkship for general surgery appears to promote their interest in a surgical career.

The Imperative of Assessing Quality of Life in Patients Presenting to a Pancreaticobiliary Surgery Clinic.

OBJECTIVE: The objective of this study was to determine baseline health-related quality of life (QoL) in patients with pancreatic adenocarcinoma, periampullary cancers, and benign pancreaticobiliary (PB) conditions at the time of the first visit to a PB surgery clinic, and to explore the relationship between QoL, demographics, clinical parameters, complications, and survival. SUMMARY BACKGROUND DATA: Few studies have examined baseline QoL measures, the impact of comorbidities, age, sex, and smoking on subsequent postoperative complications and survival in patients with pancreatic adenocarcinoma, related PB cancers, and with benign PB conditions. METHODS: Data were collected from scheduled patients at a PB surgery clinic between 2013 and 2018. The Brief Pain Inventory, Fact-Hepatobiliary Scale, and Facit-Fatigue questionnaires were administered. QoL parameters were compared between PB cancer patients and those with benign disease. RESULTS: A total of 462 individuals with PB cancers and benign diseases exhibited baseline physical well-being, functional well-being, fatigue, and overall QoL at or below the 75th percentile of wellness at the time of the first office visit. Younger age, smoking, and mental health comorbidities contributed significantly to decreased QoL. PA patients were 7 times more likely to die in the follow-up period than the benign disease group. Black patients had higher pain scores and were 3 times more likely to have a postsurgery complication. Sex differences were identified regarding fatigue, pain, and overall QoL. CONCLUSIONS: This large cohort of PB cancer and benign disease patients exhibited significantly impaired baseline QoL. GI problems, weight loss, smoking, cardiovascular, pulmonary disease, and history of anxiety and depression contributed significantly to reduced QoL. The study sheds a cautionary light on the burden of PB disease at the time of surgical evaluation and its relationship to diminished QoL.

Communicating Diagnostic Uncertainty at Emergency Department Discharge: A Simulation-Based Mastery Learning Randomized Trial.

PURPOSE: There are no standardized approaches for communicating with patients discharged from the emergency department with diagnostic uncertainty. This trial tested efficacy of the Uncertainty Communication Education Module, a simulation-based mastery learning curriculum designed to establish competency in communicating diagnostic uncertainty. METHOD: Resident physicians at 2 sites participated in a 2-arm waitlist randomized controlled trial from September 2019 to June 2020. After baseline (T1) assessment of all participants via a standardized patient encounter using the Uncertainty Communication Checklist (UCC), immediate access physicians received training in the Uncertainty Communication Education Module, which included immediate feedback, online educational modules, a smartphone-based application, and telehealth deliberate practice with standardized patients. All physicians were retested 16-19 weeks later (T2) via in-person standardized patient encounters; delayed access physicians then received the intervention. A final test of all physicians occurred 11-15 weeks after T2 (T3). The primary outcome measured the percentage of physicians in the immediate versus delayed access groups meeting or exceeding the UCC minimum passing standard at T2. RESULTS: Overall, 109 physicians were randomized, with mean age 29 years (range 25-46). The majority were male (n = 69, 63%), non-Hispanic/Latino (n = 99, 91%), and White (n = 78, 72%). At T2, when only immediate access participants had received the curriculum, immediate access physicians demonstrated increased mastery (n = 29, 52.7%) compared with delayed access physicians (n = 2, 3.7%, P < .001; estimated adjusted odds ratio of mastery for the immediate access participants, 31.1 [95% CI, 6.8-143.1]). There were no significant differences when adjusting for training site or stage of training. CONCLUSIONS: The Uncertainty Communication Education Module significantly increased mastery in communicating diagnostic uncertainty at the first postintervention test among emergency physicians in standardized patient encounters. Further work should assess the impact of clinical implementation of these communication skills.

Relapsing Polychondritis: A Case of Marked Improvement After Steroid Administration for Airway Obstruction.

Relapsing polychondritis is a rare disease that causes progressive and recurrent destruction of cartilage in the auricles, eyes, nose, and airways. A 90-year-old man was brought to the emergency department with fever, low SpO2, and effortful breathing. Arterial blood gas analysis showed that PaCO2 levels had accumulated to 120 mmHg. Although CT showed marked thickening of the bronchial wall from the central to the peripheral region, the cause was unknown. At the family's request, the patient was not placed on a ventilator, and treatment was started with steroids alone. After admission, the patient's condition improved with only intravenous steroids, and he was discharged to the facility with continued oral steroid medication. After a short treatment period, the possibility of relapsing polychondritis was considered and confirmed. The patient met Levine's diagnostic criteria, with findings of destruction of the bilateral auricular cartilage and the airway and a response to steroid administration. Although it is very difficult to diagnose relapsing polychondritis at the initial emergency department visit, early administration of steroids is worth trying in patients with asphyxia with extensive thickening of the airway on CT findings, as relapsing polychondritis may be considered, and early steroid administration may improve patient symptoms.

Semiautomatic assessment of respiratory dynamics using cine MRI in chronic obstructive pulmonary disease.

Purpose: The quantitative assessment of impaired lung motions and their association with the clinical characteristics of COPD patients is challenging. The aim of this study was to measure respiratory kinetics, including asynchronous movements, and to analyze the relationship between lung area and other clinical parameters. Materials and methods: This study enrolled 10 normal control participants and 21 COPD patients who underwent dynamic MRI and pulmonary function testing (PFT). The imaging program was implemented using MATLAB®. Each lung area was detected semi-automatically on a coronal image (imaging level at the aortic valve) from the inspiratory phase to the expiratory phase. The Dice index of the manual measurements was calculated, with the relationship between lung area ratio and other clinical parameters, including PFTs then evaluated. The asynchronous movements of the diaphragm were also evaluated using a sagittal image. Results: The Dice index for the lung region using the manual and semi-automatic extraction methods was high (Dice index = 0.97 ± 0.03). A significant correlation was observed between the time corrected lung area ratio and percentage of forced expiratory volume in 1 s (FEV1%pred) and residual volume percentage (RV%pred) (r = -0.54, p = 0.01, r = 0.50, p = 0.03, respectively). The correlation coefficient between each point of the diaphragm in the group with visible see-saw like movements was significantly lower than that in the group without see-saw like movements (value = -0.36 vs 0.95, p = 0.001). Conclusion: Semi-automated extraction of lung area from Cine MRI might be useful for detecting impaired respiratory kinetics in patients with COPD.

Weight changes in patients with sustained viral suppression switching tenofovir disoproxil fumarate to tenofovir alafenamide.

OBJECTIVE: Switching from tenofovir disoproxil fumarate (TDF)- to tenofovir alafenamide (TAF)-containing antiretroviral therapy may negatively influence weight, cholesterol, and atherosclerotic cardiovascular disease risk. The extent of these changes and their association with TAF remain unclear. METHODS: This retrospective cohort evaluated metabolic changes in virologically suppressed patients with HIV infection who switched from TDF to TAF without switching other antiretroviral therapy medications. Adult patients on TDF and with no HIV viral load values >200 copies/mL for ≥2 years prior to and following a TAF switch were included. Weight and other variables were collected for 2 years before and after the switch. Longitudinal linear mixed-effects models evaluated changes at 1 and 2 years after the switch. RESULTS: In the unadjusted analysis, there were increases in weight, BMI, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, fasting glucose, and atherosclerotic cardiovascular disease risk scores 2 years after switching to TAF (each p ≤ 0.03). However, only increases in total and low-density lipoprotein cholesterol were associated with TAF and were significantly different from expected changes predicted in the adjusted longitudinal models. CONCLUSIONS: Despite observing significant unadjusted metabolic changes after switching to TAF, only changes in cholesterol were associated with TAF and were different from changes expected in time-trend adjusted models.

Analysis of cost and outcomes in bony versus soft tissue midface free flap reconstruction.

BACKGROUND: Outcomes and cost of soft tissue versus bony midface free flap reconstruction (MR) with and without virtual surgical planning (VSP) were evaluated. METHODS: Retrospective review of MR including ischemic time (IT), operative duration (OD), length of stay (LOS), and total cost (TC). Eighty-one soft tissue and 76 bony MR (VSP = 23) were reviewed. RESULTS: Bony MR was used for higher complexity defects (p = 0.003) and was associated with higher IT (p < 0.001), OD (p < 0.001), LOS (p = 0.032), and TC (p < 0.001). VSP was associated with a mean 111.2 ± 37.9 minute reduction in OD (p = 0.004) compared to non-VSP bony flaps. VSP was associated with higher itemized cost, but no increase in TC (p = 0.327). CONCLUSIONS: Bony MR was used for higher complexity MR and was associated with increased TC, LOS, OD, and IT. VSP shortened OD with no significant increase in TC.

COVID-19-Associated Pulmonary Aspergillosis in a Patient Treated With Remdesivir, Dexamethasone, and Baricitinib: A Case Report.

Remdesivir, dexamethasone, and baricitinib have recently been used to treat patients with coronavirus disease 2019 (COVID-19) and respiratory failure. However, the adverse effects of combination therapy have not been fully explored. A 64-year-old man was diagnosed with COVID-19 and was treated with remdesivir, dexamethasone, and baricitinib. His respiratory condition worsened on day 17, and in the following days, he was diagnosed with pneumomediastinum and COVID-19-associated pulmonary aspergillosis (CAPA). His condition improved with a reduction in the corticosteroid regime and antifungal treatment. This is the first case of pulmonary aspergillosis in a patient with COVID-19 that was treated with remdesivir, dexamethasone, and baricitinib.

A Pilot Feasibility Study of Digital Health Coaching for Men With Prostate Cancer.

PURPOSE: Prostate cancer is the most common cancer among men in the United States. The majority of prostate cancer treatment occurs in the ambulatory setting, and patients and their caregivers take on significant responsibility for monitoring and managing treatment and disease-related toxicity. Digital health coaching has shown promise as a tool to positively influence outcomes. We completed a single-arm pilot study to assess the feasibility of digital health coaching in men with prostate cancer. METHODS: Men with a history of prostate cancer requiring treatment in the past 2 years were eligible for inclusion. Participants engaged in a 12-week health coaching program, consisting of a combination of at least one telephone call and up to four digital nudges (defined as content delivered via text, e-mail, or app on the basis of the participant's preference) per week. Prostate cancer-specific content addressed one of the following topics each week: fatigue, pain management, healthy eating, exercise, managing incontinence, sexual health, managing stress and anxiety, financial toxicity, goal setting during treatment, managing side effects, communicating with the health care team, and medication adherence. Services were provided at no cost to the participant. RESULTS: A hundred patients were consented for the study, and 88 enrolled. The feasibility threshold of 60% was met with 63 of the 88 enrolled individuals completing the 3-month program (proportion = 71.6%; 90% CI, 62.6 to 79.4; P = .016). CONCLUSION: Digital health coaching for men with prostate cancer is feasible. These findings support further evaluation of digital health coaching for men with prostate cancer in larger randomized controlled trials.

Utility of Concurrent Surgical Treatment Strategy with Thoracoscopic Esophagectomy for Patients with Synchronous Esophageal and Head and Neck Cancer.

Background: Patients with esophageal squamous cell cancer (ESCC) have a high frequency to coincide with head and neck cancer (HNC). This study aims to analyze the treatment results and prognosis of patients with synchronous ESCC and HNC. Methods: From January 2016 to December 2019, 5 patients underwent concurrent surgical resection of synchronous ESCC and HNC in our institution. We retrospectively reviewed the surgical outcomes and prognosis of these patients with synchronous ESCC and HNC (HNEC group) and compared the results with those of 20 patients who underwent esophagectomy with three regional lymph node dissections for ESCC during the same period (EC group). Results: The locations of HNCs were pharynx/tongue (4/1) and the clinical stages were Stage IV in all patients. Meanwhile, the clinical stages of ESCCs were Stages 0/I/II/III (1/1/2/1). All patients underwent thoracoscopic esophagectomy. The surgical procedures concurrently performed for HNC were pharyngolaryngectomy with free jejunum transfer in 3 patients, wide tongue and mandibular segment resection with mandibular reconstruction in 1 patient, and mandibular transection with radial forearm flap reconstruction in 1 patient. There was no significant difference in the frequency of postoperative complication between these two groups. The HNEC group had a significantly shorter recurrence-free survival than the EC group (P = .046). Conclusion: Head and neck surgery with thoracoscopic esophagectomy can be safely performed concurrently with local control. The risk of recurrence is higher in ESCC patients with HNC; therefore, it is important to move on to adjuvant therapy without delay.

Outreach to primary care patients in lung cancer screening: A randomized controlled trial.

Current guidelines recommend annual lung cancer screening (LCS), but rates are low. The current study evaluated strategies to increase LCS. This study was a randomized controlled trial designed to evaluate the effects of patient outreach and shared decision making (SDM) about LCS among patients in four primary care practices. Patients 50 to 80 years of age and at high risk for lung cancer were randomized to Outreach Contact plus Decision Counseling (OC-DC, n = 314), Outreach Contact alone (OC, n = 314), or usual care (UC, n = 1748). LCS was significantly higher in the combined OC/OC-DC group versus UC controls (5.5% vs. 1.8%; hazard ratio, HR = 3.28; 95% confidence interval, CI: 1.98 to 5.41; p = 0.001). LCS was higher in the OC-DC group than in the OC group, although not significantly so (7% vs. 4%, respectively; HR = 1.75; 95% CI: 0.86 to 3.55; p = 0.123). LCS referral/scheduling was also significantly higher in the OC/OC-DC group compared to controls (11% v. 5%; odds ratio, OR = 2.02; p = 0.001). We observed a similar trend for appointment keeping, but the effect was not statistically significant (86% v. 76%; OR = 1.93; p = 0.351). Outreach contacts significantly increased LCS among primary care patients. Research is needed to assess the additional value of SDM on screening uptake.

Targeting SOX10-deficient cells to reduce the dormant-invasive phenotype state in melanoma.

Cellular plasticity contributes to intra-tumoral heterogeneity and phenotype switching, which enable adaptation to metastatic microenvironments and resistance to therapies. Mechanisms underlying tumor cell plasticity remain poorly understood. SOX10, a neural crest lineage transcription factor, is heterogeneously expressed in melanomas. Loss of SOX10 reduces proliferation, leads to invasive properties, including the expression of mesenchymal genes and extracellular matrix, and promotes tolerance to BRAF and/or MEK inhibitors. We identify the class of cellular inhibitor of apoptosis protein-1/2 (cIAP1/2) inhibitors as inducing cell death selectively in SOX10-deficient cells. Targeted therapy selects for SOX10 knockout cells underscoring their drug tolerant properties. Combining cIAP1/2 inhibitor with BRAF/MEK inhibitors delays the onset of acquired resistance in melanomas in vivo. These data suggest that SOX10 mediates phenotypic switching in cutaneous melanoma to produce a targeted inhibitor tolerant state that is likely a prelude to the acquisition of resistance. Furthermore, we provide a therapeutic strategy to selectively eliminate SOX10-deficient cells.