Stepped Palliative Care for Patients With Advanced Lung Cancer: A Randomized Clinical Trial.

Importance: Despite the evidence for early palliative care improving outcomes, it has not been widely implemented in part due to palliative care workforce limitations. Objective: To evaluate a stepped-care model to deliver less resource-intensive and more patient-centered palliative care for patients with advanced cancer. Design, Setting, and Participants: Randomized, nonblinded, noninferiority trial of stepped vs early palliative care conducted between February 12, 2018, and December 15, 2022, at 3 academic medical centers in Boston, Massachusetts, Philadelphia, Pennsylvania, and Durham, North Carolina, among 507 patients who had been diagnosed with advanced lung cancer within the past 12 weeks. Intervention: Step 1 of the intervention was an initial palliative care visit within 4 weeks of enrollment and subsequent visits only at the time of a change in cancer treatment or after a hospitalization. During step 1, patients completed a measure of quality of life (QOL; Functional Assessment of Cancer Therapy-Lung [FACT-L]; range, 0-136, with higher scores indicating better QOL) every 6 weeks, and those with a 10-point or greater decrease from baseline were stepped up to meet with the palliative care clinician every 4 weeks (intervention step 2). Patients assigned to early palliative care had palliative care visits every 4 weeks after enrollment. Main Outcomes and Measures: Noninferiority (margin = -4.5) of the effect of stepped vs early palliative care on patient-reported QOL on the FACT-L at week 24. Results: The sample (n = 507) mostly included patients with advanced non-small cell lung cancer (78.3%; mean age, 66.5 years; 51.4% female; 84.6% White). The mean number of palliative care visits by week 24 was 2.4 for stepped palliative care and 4.7 for early palliative care (adjusted mean difference, -2.3; P < .001). FACT-L scores at week 24 for the stepped palliative care group were noninferior to scores among those receiving early palliative care (adjusted FACT-L mean score, 100.6 vs 97.8, respectively; difference, 2.9; lower 1-sided 95% confidence limit, -0.1; P < .001 for noninferiority). Although the rate of end-of-life care communication was also noninferior between groups, noninferiority was not demonstrated for days in hospice (adjusted mean, 19.5 with stepped palliative care vs 34.6 with early palliative care; P = .91). Conclusions and Relevance: A stepped-care model, with palliative care visits occurring only at key points in patients' cancer trajectories and using a decrement in QOL to trigger more intensive palliative care exposure, resulted in fewer palliative care visits without diminishing the benefits for patients' QOL. While stepped palliative care was associated with fewer days in hospice, it is a more scalable way to deliver early palliative care to enhance patient-reported outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT03337399.

Preliminary Outcomes of Scapholunate Ligament Augmentation with Internal Brace Technique.

Purpose: Injury to the scapholunate (SL) interosseous ligament (SLIL) is a common cause of carpal instability. Internal brace augmentation has been used in various ligament repair procedures; however, further investigation of its outcomes in hand surgery is needed. This study aimed to examine outcomes for patients who underwent SLIL repair with internal brace augmentation. Methods: Patients who underwent SLIL repair with the internal brace technique and had at least 1 year of follow-up were contacted. Available patients returned for an in-person evaluation with new radiographs and physical examination. If patients could not be contacted but had x-rays and physical examinations performed at greater than 1 year after surgery, these data were collected from their medical records. Participating patients completed the QuickDASH and Patient-Rated Wrist Evaluation surveys and rated their satisfaction with the surgery. Outcomes assessed included wrist range of motion, grip strength, scaphoid shift test, SL gap, SL angle, and radiographic evidence of radiocarpal arthritis. Results: We collected outcomes for 14 SLIL repairs among 13 patients (12 male). Mean length of the follow-up was 41 months (n = 14, 17-64). Mean QuickDASH and Patient-Rated Wrist Evaluation scores were 6.1 (0-43.2) and 9.6 (0-65), respectively. Radiographic measurements remained stable from immediate to latest follow-up, and no radiocarpal arthritic changes were noted. However, SL gap decreased from a mean of 5.33 mm (3.4-6.7) before surgery to 3.34 mm (2-4.6) at the latest follow-up, and SL angle decreased from a mean of 79.5° (67°-97°) before surgery to 67.3° (51°-85°) at the latest follow-up. All scaphoid shift tests were stable. Conclusions: Therefore, SL internal brace augmentation has favorable short-term results with improvements in pain, function, satisfaction, and carpal alignment at greater than 1 year postoperatively. This technique can be an effective option for the management of SL instability in the short term. Type of study/level of evidence: Therapeutic IV.

Corrigendum to "Androgen Deprivation and Radiotherapy with or Without Docetaxel for Localized High-risk Prostat Cancer: Long-term Follow-up from the Randomized NRG Oncology RTOG 0521 Trial" [Eur. Eurol. 84(2) (2023) 156-163].

BACKGROUND: Intensification of therapy may improve outcomes for patients with high-risk localized prostate cancer. OBJECTIVE: To provide long-term follow-up data from phase III RTOG 0521, which compared a combination of androgen deprivation therapy (ADT) + external beam radiation therapy (EBRT) + docetaxel with ADT + EBRT. DESIGN, SETTING, AND PARTICIPANTS: High-risk localized prostate cancer patients (>50% of patients had Gleason 9-10 disease) were prospectively randomized to 2 yr of ADT + EBRT or ADT + EBRT + six cycles of docetaxel. A total of 612 patients were accrued, and 563 were eligible and included in the modified intent-to-treat analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was overall survival (OS). Analyses with Cox proportional hazards were performed as prespecified in the protocol; however, there was evidence of nonproportional hazards. Thus, a post hoc analysis was performed using the restricted mean survival time (RMST). The secondary endpoints included biochemical failure, distant metastasis (DM) as detected by conventional imaging, and disease-free survival (DFS). RESULTS AND LIMITATIONS: After 10.4 yr of median follow-up among survivors, the hazard ratio (HR) for OS was 0.89 (90% confidence interval [CI] 0.70-1.14; one-sided log-rank p = 0.22). Survival at 10 yr was 64% for ADT + EBRT and 69% for ADT + EBRT + docetaxel. The RMST at 12 yr was 0.45 yr and not statistically significant (one-sided p = 0.053). No differences were detected in the incidence of DFS (HR = 0.92, 95% CI 0.73-1.14), DM (HR = 0.84, 95% CI 0.73-1.14), or prostate-specific antigen recurrence risk (HR = 0.97, 95% CI 0.74-1.29). Two patients had grade 5 toxicity in the chemotherapy arm and zero patients in the control arm. CONCLUSIONS: After a median follow-up of 10.4 yr among surviving patients, no significant differences are observed in clinical outcomes between the experimental and control arms. These data suggest that docetaxel should not be used for high-risk localized prostate cancer. Additional research may be warranted using novel predictive biomarkers. PATIENT SUMMARY: No significant differences in survival were noted after long-term follow-up for high-risk localized prostate cancer patients in a large prospective trial where patients were treated with androgen deprivation therapy + radiation to the prostate ± docetaxel.

Dangerous Variation or Patient-Centered Care? Palliative Care and Pain Providers' Comfort, Experiences, and Approaches when Treating Cancer Pain With Coexisting Aberrant Behaviors.

BACKGROUND: Patients with cancer-related pain are at high risk for aberrant drug use behaviors (ADB), including self-escalation, diversion and concurrent illicit substance or opioid misuse; however, limited evidence is available to guide opioid prescribing for patients with life-limiting illness and concurrent or suspected ADB. We sought to characterize how specialists evaluate for and manage these high-risk behaviors in patients with cancer-related pain. METHODS: We conducted telephonic semi-structured interviews with palliative care and pain medicine providers. Participants discussed their own comfort and experience level with identifying and managing ADB in patients with life-limiting illness. They were subsequently presented with a series of standardized scenarios and asked to describe their concerns and management strategies. RESULTS: 95 interdisciplinary pain and palliative care specialists were contacted; 37 agreed to participate (38.9%). Analysis of interview contents revealed several central themes: (1) widespread discomfort and anxiety regarding safe and compassionate opioid prescribing for high-risk patients, (2) belief that widely used risk-mitigation tools such as opioid contracts and urine drug screens provided inadequate support for decision-making, and (3) lack of institutional and organizational support and guidance for safe prescribing strategies. Most clinicians reported self-education regarding addiction and alternative prescribing/pain management strategies. Providers varied widely in their willingness to discontinue opioid prescribing in a patient with aberrant behavior and pain associated with life-limiting illness. CONCLUSION: Providers caring for patients demonstrating ADB and cancer-related pain struggle to balance safe prescribing with symptom management. Increased guidance is needed regarding opioid prescribing, monitoring, and discontinuation in high-risk patients.

Advances in diagnosis and management of cancer of the esophagus.

Esophageal cancer is the seventh most common malignancy worldwide, with over 470 000 new cases diagnosed each year. Two distinct histological subtypes predominate, and should be considered biologically separate disease entities.1 These subtypes are esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). Outcomes remain poor regardless of subtype, with most patients presenting with late stage disease.2 Novel strategies to improve early detection of the respective precursor lesions, squamous dysplasia, and Barrett's esophagus offer the potential to improve outcomes. The introduction of a limited number of biologic agents, as well as immune checkpoint inhibitors, is resulting in improvements in the systemic treatment of locally advanced and metastatic esophageal cancer. These developments, coupled with improvements in minimally invasive surgical and endoscopic treatment approaches, as well as adaptive and precision radiotherapy technologies, offer the potential to improve outcomes still further. This review summarizes the latest advances in the diagnosis and management of esophageal cancer, and the developments in understanding of the biology of this disease.

Chronic suppurative otitis media.

Chronic suppurative otitis media (CSOM) is a leading global cause of potentially preventable hearing loss in children and adults, associated with socioeconomic deprivation. There is an absence of consensus on the definition of CSOM, which complicates efforts for prevention, treatment, and monitoring. CSOM occurs when perforation of the tympanic membrane is associated with severe or persistent inflammation in the middle ear, leading to hearing loss and recurrent or persistent ear discharge (otorrhoea). Cholesteatoma, caused by the inward growth of the squamous epithelium of the tympanic membrane into the middle ear, can also occur. The optimal treatment of discharge in CSOM is topical antibiotics. In resource-limited settings where topical antibiotics might not be available, topical antiseptics are an alternative. For persistent disease, surgery to repair the tympanic membrane or remove cholesteatoma might offer long-term resolution of otorrhoea and potential improvement to hearing. Recent developments in self-fitted air-conduction and bone-conduction hearing aids offer promise as new options for rehabilitation.

Gas-Induced Electrical and Magnetic Modulation of Two-Dimensional Conductive Metal-Organic Framework.

Controlled modulation of electronic and magnetic properties in stimuli-responsive materials provides valuable insights for the design of magnetoelectric or multiferroic devices. This paper demonstrates the modulation of electrical and magnetic properties of a semiconductive, paramagnetic metal-organic framework (MOF) Cu3(C6O6)2 with small gaseous molecules, NH3, H2S, and NO. This study merges chemiresistive and magnetic tests to reveal that the MOF undergoes simultaneous changes in electrical conductance and magnetization that are uniquely modulated by each gas. The features of response, including direction, magnitude, and kinetics, are modulated by the physicochemical properties of the gaseous molecules. This study advances the design of multifunctional materials capable of undergoing simultaneous changes in electrical and magnetic properties in response to chemical stimuli.

A novel classification of intraoperative ulnar nerve instability to aid transposition surgery.

HYPOTHESIS: The purpose of this study was to compare inter- and intraobserver agreement of a novel intraoperative subluxation classification for patients undergoing ulnar nerve surgery at the elbow. We hypothesize there will be strong inter- and intraobserver agreement of the 4-category classification system, and reviewers will have substantial confidence while reviewing the classification system. METHODS: Four blinded fellowship-trained orthopedic hand surgeons reviewed 25 videos in total on 2 separate viewings, 21 days apart. Variables collected were ulnar subluxation classification (A, B, C, or D) and a confidence metric. Subsequent to primary data collection, classification grading was stratified into A/B or C/D subgroups for further analysis. Cohen κ scores were used to evaluate all variables collected in this study. The interpretation of κ scores included ≤0.0 as no agreement, 0.01-0.20 as none to slight, 0.21-0.40 as fair, 0.41-0.60 as moderate, 0.61-0.80 as substantial, and 0.81-1.0 as almost perfect agreement. RESULTS: Interobserver agreement of subluxation classification as a 4-category scale demonstrated a moderate agreement on first viewing, second viewing, and when both viewings were combined (κ = 0.51, 0.51, and 0.51 respectively). Seventy-five percent (3 of 4) of reviewers had moderate intraobserver agreement for ulnar nerve subluxation classification, whereas 1 reviewer had substantial intraobserver classification (κ = 0.72). Overall, there was high confidence in 65% of classification scores in the second round of viewing, which improved from 58% in the first viewing round. When ulnar subluxation classification selections were regrouped into classes A/B or C/D, 100% of reviewers had substantial interobserver (κ = 0.74-0.75) and substantial to almost perfect intraobserver (κ = 0.71-0.91) agreement. CONCLUSIONS: The 4-category classification was reproducible within and between reviewers. Agreement appeared to increase when simplifying the classification to 2 categories, which may provide guidance to surgical decision making. The validation of a reproducible classification scheme for intraoperative ulnar subluxation may aid with decision making and further postoperative outcomes research.

A systematic review of circulating predictive and prognostic biomarkers to aid the personalised use of radiotherapy in the radical treatment of patients with oesophageal cancer.

BACKGROUND: The availability of circulating biomarkers that are predictive of treatment response or prognostic of overall outcome could enable the personalised and adaptive use of radiotherapy (RT) in patients with oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC). METHODS: A systematic review was carried out following Preferred Reporting Items for Systematic Reviews guidance. Medline, EMBASE, PubMed, Cochrane Library, CINAHL, Scopus and the Web of Science databases were searched for studies published between January 2005-February 2023 relating to circulating biomarkers evaluated in the context of neoadjuvant or definitive RT delivered for OAC/OSCC. Study quality was assessed using predefined criteria. RESULTS: A total of 3012 studies were screened and 57 subsequently included, across which 61 biomarkers were reported. A majority (43/57,75.4%) of studies were of Asian origin and retrospective (40/57, 70.2%), with most (52/57, 91.2%) biomarkers reported in the context of patients with OSCC. There was marked inter-study heterogeneity in patient populations, treatment characteristics, biomarker measurement and the cut points used to define biomarker positivity. Nevertheless, there is evidence for the prognostic and predictive value of circulating tumour DNA and numerous miRNAs in OAC and OSCC, as well as for the prognostic and predictive value of circulating levels of CYFRA21.1 in OSCC. CONCLUSIONS: There is consistent evidence for the potential predictive and prognostic value of a small number of biomarkers in OSCC and OAC, though these data are insufficient for translation to current clinical practice. Well-designed prospective studies are now required to validate their role in stratified and personalised RT treatment approaches.

Practical Considerations When Choosing Chemoembolization versus Radioembolization for Hepatocellular Carcinoma.

Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) are common liver-directed therapies (LDTs) for unresectable HCC. While both deliver intra-arterial treatment directly to the site of the tumor, they differ in mechanisms of action and side effects. Several studies have compared their side effect profile, time to progression, and overall survival data, but often these lack practical considerations when choosing which treatment modality to use. Many factors can impact operator's choice for treatment, and the choice depends on treatment availability, cost, insurance coverage, operator's comfort level, patient-specific factors, tumor location, tumor biology, and disease stage. This review discusses survival data, time to progression data, as well as more practical patient and tumor characteristics for personalized LDT with TACE or TARE.

Post-traumatic stress and future substance use outcomes: leveraging antecedent factors to stratify risk.

Background: Post-traumatic stress disorder (PTSD) and substance use (tobacco, alcohol, and cannabis) are highly comorbid. Many factors affect this relationship, including sociodemographic and psychosocial characteristics, other prior traumas, and physical health. However, few prior studies have investigated this prospectively, examining new substance use and the extent to which a wide range of factors may modify the relationship to PTSD. Methods: The Advancing Understanding of RecOvery afteR traumA (AURORA) study is a prospective cohort of adults presenting at emergency departments (N = 2,943). Participants self-reported PTSD symptoms and the frequency and quantity of tobacco, alcohol, and cannabis use at six total timepoints. We assessed the associations of PTSD and future substance use, lagged by one timepoint, using the Poisson generalized estimating equations. We also stratified by incident and prevalent substance use and generated causal forests to identify the most important effect modifiers of this relationship out of 128 potential variables. Results: At baseline, 37.3% (N = 1,099) of participants reported likely PTSD. PTSD was associated with tobacco frequency (incidence rate ratio (IRR): 1.003, 95% CI: 1.00, 1.01, p = 0.02) and quantity (IRR: 1.01, 95% CI: 1.001, 1.01, p = 0.01), and alcohol frequency (IRR: 1.002, 95% CI: 1.00, 1.004, p = 0.03) and quantity (IRR: 1.003, 95% CI: 1.001, 1.01, p = 0.001), but not with cannabis use. There were slight differences in incident compared to prevalent tobacco frequency and quantity of use; prevalent tobacco frequency and quantity were associated with PTSD symptoms, while incident tobacco frequency and quantity were not. Using causal forests, lifetime worst use of cigarettes, overall self-rated physical health, and prior childhood trauma were major moderators of the relationship between PTSD symptoms and the three substances investigated. Conclusion: PTSD symptoms were highly associated with tobacco and alcohol use, while the association with prospective cannabis use is not clear. Findings suggest that understanding the different risk stratification that occurs can aid in tailoring interventions to populations at greatest risk to best mitigate the comorbidity between PTSD symptoms and future substance use outcomes. We demonstrate that this is particularly salient for tobacco use and, to some extent, alcohol use, while cannabis is less likely to be impacted by PTSD symptoms across the strata.

#4Corners4Health Social Media Cancer Prevention Campaign for Emerging Adults: Protocol for a Randomized Stepped-Wedge Trial.

BACKGROUND: Many emerging adults (EAs) are prone to making unhealthy choices, which increase their risk of premature cancer morbidity and mortality. In the era of social media, rigorous research on interventions to promote health behaviors for cancer risk reduction among EAs delivered over social media is limited. Cancer prevention information and recommendations may reach EAs more effectively over social media than in settings such as health care, schools, and workplaces, particularly for EAs residing in rural areas. OBJECTIVE: This pragmatic randomized trial aims to evaluate a multirisk factor intervention using a social media campaign designed with community advisers aimed at decreasing cancer risk factors among EAs. The trial will target EAs from diverse backgrounds living in rural counties in the Four Corners states of Arizona, Colorado, New Mexico, and Utah. METHODS: We will recruit a sample of EAs (n=1000) aged 18 to 26 years residing in rural counties (Rural-Urban Continuum Codes 4 to 9) in the Four Corners states from the Qualtrics' research panel and enroll them in a randomized stepped-wedge, quasi-experimental design. The inclusion criteria include English proficiency and regular social media engagement. A social media intervention will promote guideline-related goals for increased physical activity, healthy eating, and human papillomavirus vaccination and reduced nicotine product use, alcohol intake, and solar UV radiation exposure. Campaign posts will cover digital and media literacy skills, responses to misinformation, communication with family and friends, and referral to community resources. The intervention will be delivered over 12 months in Facebook private groups and will be guided by advisory groups of community stakeholders and EAs and focus groups with EAs. The EAs will complete assessments at baseline and at 12, 26, 39, 52, and 104 weeks after randomization. Assessments will measure 6 cancer risk behaviors, theoretical mediators, and participants' engagement with the social media campaign. RESULTS: The trial is in its start-up phase. It is being led by a steering committee. Team members are working in 3 subcommittees to optimize community engagement, the social media intervention, and the measures to be used. The Stakeholder Organization Advisory Board and Emerging Adult Advisory Board were formed and provided initial input on the priority of cancer risk factors to target, social media use by EAs, and community resources available. A framework for the social media campaign with topics, format, and theoretical mediators has been created, along with protocols for campaign management. CONCLUSIONS: Social media can be used as a platform to counter misinformation and improve reliable health information to promote health behaviors that reduce cancer risks among EAs. Because of the popularity of web-based information sources among EAs, an innovative, multirisk factor intervention using a social media campaign has the potential to reduce their cancer risk behaviors. TRIAL REGISTRATION: ClinicalTrials.gov NCT05618158; https://classic.clinicaltrials.gov/ct2/show/NCT05618158. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/50392.

Multimodal Pain Management After Outpatient Orthopedic Hand Surgery: A Prospective Randomized Trial.

Purpose: Opioid stewardship ensures effective pain management while avoiding overprescribing of opioids after surgery. This prospective randomized study investigates the efficacy of a multimodal postoperative pain regimen compared to a traditional opioid-only pain regimen following elective outpatient orthopedic hand surgery. We hypothesized that patients receiving multimodal pain management would consume fewer opioids and report greater satisfaction than patients receiving only opioids. Methods: Consecutive patients undergoing outpatient hand and upper extremity surgery performed by two board-certified fellowship-trained orthopedic hand surgeons at one institution were recruited and randomized into either a study or control group. The study group received a standing multimodal postoperative regimen consisting of scheduled oral acetaminophen and naproxen as well as oxycodone to be taken as needed. The control group received only oxycodone to be taken as needed. Postoperatively, daily pain levels, medication usage, refills, satisfaction, and adverse events were recorded. Descriptive statistics were performed. Results: Of the 112 patients enrolled, 54 were randomized to the control group, and 58 were randomized to the study group. Study and control group patients did not differ significantly based on daily average pain scores or daily worst pain scores. However, study group patients reported fewer average daily oxycodone intake and total oxycodone pill count (7.0 vs 2.4 total pills, P <.005). In addition, the study group patients were more likely to report satisfaction with their postoperative pain control than control regimen patient's and were more likely to use the same pain regimen again if required. Conclusion: A multimodal postoperative pain regimen reduces opioid usage and has higher patient satisfaction rates in comparison to traditional opioid-only regimens. Use of multimodal pain regimens that use nonopioids, such as acetaminophen and naproxen, over an opioid should be considered for postoperative pain after orthopedic hand surgery. Level of Evidence: Therapeutic II.

Outcomes Following Fully Threaded Intramedullary Nailing of Metacarpal Fractures.

Purpose: Intramedullary screw fixation has emerged as a popular approach for the treatment of displaced metacarpal fractures. The purpose of this study was to investigate the functional and radiographic outcomes of a newly designed, headless noncompressive fully threaded intramedullary nail (TIMN) for the treatment of metacarpal fractures. Methods: A retrospective chart review was performed on patients who were treated with the INnate TIMN (ExsoMed) at a single academic institution with a minimum of 1-year follow-up. Patient-reported functional outcomes included Quick Disabilities for the Arm, Shoulder, and Hand (QuickDASH) questionnaires, return to work and physical activity time, and overall satisfaction. Radiographs were retrospectively reviewed to determine radiographic union, change in angulation, and metacarpal shortening. Results: A total of 49 patients (58 fractures) with a mean age of 36 years (range: 17-75 years) were included. The mean follow-up time was 2.7 years (range: 1.4-4.3 years). Overall, the mean patient satisfaction rating was 4.9 of 5 (range: 3-5). The mean return to work time was 7.2 weeks (range: 0.14-28 weeks), and the mean return to sport or activity was 8.3 weeks (range: 1-28 weeks). Average QuickDASH scores across all patients were 4 (range: 0-56.9). The median radiographic healing time was 6.1 weeks (range: 4.7-15.4 weeks). Mean postoperative shortening in the fifth metacarpal fracture was 3 mm (range: -4.2 to 8 mm) at the initial postoperative visit and 3.6 mm (range: -3.3 to 7.9 mm) at the final radiographic follow-up. Subgroup analysis showed that postoperative shortening was similar, regardless of the fracture pattern. The following four complications were reported: one case of persistent pain and stiffness, one case of carpal tunnel syndrome, one nonunion, and one fractured intramedullary nail. Conclusions: Our findings suggest that the TIMN allows for a reliable return to work and physical activity, high patient satisfaction, low complication rate, and minimal shortening at the final radiographic follow-up. Type of study/level of evidence: Therapeutic IV.

External Validation of a Digital Pathology-based Multimodal Artificial Intelligence Architecture in the NRG/RTOG 9902 Phase 3 Trial.

BACKGROUND: Accurate risk stratification is critical to guide management decisions in localized prostate cancer (PCa). Previously, we had developed and validated a multimodal artificial intelligence (MMAI) model generated from digital histopathology and clinical features. Here, we externally validate this model on men with high-risk or locally advanced PCa treated and followed as part of a phase 3 randomized control trial. OBJECTIVE: To externally validate the MMAI model on men with high-risk or locally advanced PCa treated and followed as part of a phase 3 randomized control trial. DESIGN, SETTING, AND PARTICIPANTS: Our validation cohort included 318 localized high-risk PCa patients from NRG/RTOG 9902 with available histopathology (337 [85%] of the 397 patients enrolled into the trial had available slides, of which 19 [5.6%] failed due to poor image quality). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Two previously locked prognostic MMAI models were validated for their intended endpoint: distant metastasis (DM) and PCa-specific mortality (PCSM). Individual clinical factors and the number of National Comprehensive Cancer Network (NCCN) high-risk features served as comparators. Subdistribution hazard ratio (sHR) was reported per standard deviation increase of the score with corresponding 95% confidence interval (CI) using Fine-Gray or Cox proportional hazards models. RESULTS AND LIMITATIONS: The DM and PCSM MMAI algorithms were significantly and independently associated with the risk of DM (sHR [95% CI] = 2.33 [1.60-3.38], p < 0.001) and PCSM, respectively (sHR [95% CI] = 3.54 [2.38-5.28], p < 0.001) when compared against other prognostic clinical factors and NCCN high-risk features. The lower 75% of patients by DM MMAI had estimated 5- and 10-yr DM rates of 4% and 7%, and the highest quartile had average 5- and 10-yr DM rates of 19% and 32%, respectively (p < 0.001). Similar results were observed for the PCSM MMAI algorithm. CONCLUSIONS: We externally validated the prognostic ability of MMAI models previously developed among men with localized high-risk disease. MMAI prognostic models further risk stratify beyond the clinical and pathological variables for DM and PCSM in a population of men already at a high risk for disease progression. This study provides evidence for consistent validation of our deep learning MMAI models to improve prognostication and enable more informed decision-making for patient care. PATIENT SUMMARY: This paper presents a novel approach using images from pathology slides along with clinical variables to validate artificial intelligence (computer-generated) prognostic models. When implemented, clinicians can offer a more personalized and tailored prognostic discussion for men with localized prostate cancer.

Posterior Interosseous Neuropathy Related to a Loose Distal Biceps Cortical Button: A Case Series.

Posterior interosseous nerve (PIN) injury is an uncommon yet debilitating complication following distal bicep tendon repair. There are case reports of acute intraoperative PIN injury related to retractor placement, drill trajectory, and nerve incarceration. We report three cases of delayed PIN neuropathy in the setting of a loose cortical button. All patients had resolution of their pain with removal of the cortical button and decompression of the radial tunnel. The purpose of this case series is to: 1) highlight the possibility of a loose cortical bicep button as the cause of proximal forearm pain and PIN neuropathy in the early or late postoperative timeframe; and 2) emphasize the importance of proper surgical technique and use of intraoperative fluoroscopy to assure the cortical button is well-fixed and flush with the radial shaft. .

Surrogate endpoints in clinical trials of p16-positive squamous cell carcinoma of the oropharynx: an individual patient data meta-analysis.

BACKGROUND: The increased incidence of human papillomavirus (HPV)-related cancers has motivated efforts to optimise treatment for these patients with excellent prognosis. Validation of surrogates for overall survival could expedite the investigation of new therapies. We sought to evaluate candidate intermediate clinical endpoints in trials assessing definitive treatment of p16-positive oropharyngeal cancer with chemotherapy or radiotherapy. METHODS: We did a retrospective review of five multicentre, randomised trials (NRG/RTOG 9003, 0129, 0234, 0522, and 1016) that tested radiotherapy with or without chemotherapy in patients (aged ≥18 years) with p16-positive localised head or neck squamous-cell carcinomas. Eight intermediate clinical endpoints were considered as potential surrogates for overall survival: freedom from local progression, freedom from regional progression, freedom from distant metastasis, freedom from locoregional progression, freedom from any progression, locoregional progression-free survival, progression-free survival, and distant metastasis-free survival. We used a two-stage meta-analytical framework, which requires high correlation between the intermediate clinical endpoint and overall survival at the patient level (condition 1), and high correlation between the treatment effect on the intermediate clinical endpoint and the treatment effect on overall survival (condition 2). For both, an r2 greater than 0·7 was used as criteria for clinically relevant surrogacy. FINDINGS: We analysed 1373 patients with oropharyngeal cancer from May 9, 2020, to Nov 22, 2023. 1231 (90%) of patients were men, 142 (10%) were women, and 1207 (88%) were White, with a median age of 57 years (IQR 51-62). Median follow-up was 4·2 years (3·1-5·1). For the first condition, correlating the intermediate clinical endpoints with overall survival at the individual and trial level, the three composite endpoints of locoregional progression-free survival (Kendall's τ 0·91 and r2 0·72), distant metastasis-free survival (Kendall's τ 0·93 and r2 0·83), and progression-free survival (Kendall's τ 0·88 and r2 0·70) were highly correlated with overall survival at the patient level and at the trial-group level. For the second condition, correlating treatment effects of the intermediate clinical endpoints and overall survival, the composite endpoints of locoregional progression-free survival (r2 0·88), distant metastasis-free survival (r2 0·96), and progression-free survival (r2 0·92) remained strong surrogates. Treatment effects on the remaining intermediate clinical endpoints were less strongly correlated with overall survival. INTERPRETATION: We identified locoregional progression-free survival, distant metastasis-free survival, and progression-free survival as surrogates for overall survival in p16-positive oropharyngeal cancers treated with chemotherapy or radiotherapy, which could serve as clinical trial endpoints. FUNDING: NRG Oncology Operations, NRG Oncology SDMC, the National Cancer Institute, Eli Lilly, Aventis, and the University of Michigan.

Utilizing Stems in Primary Total Knee Arthroplasty: Analysis of the Australian Orthopaedic Association National Joint Replacement Registry Data.

BACKGROUND: We compared revision rates and reasons for revision for primary total knee arthroplasty (TKA) performed for osteoarthritis with and without tibial stem extensions. METHODS: Data from the Australian Orthopaedic Association National Joint Replacement Registry were used to compare all-cause revision, reason, and type of revision between primary TKA using stemmed tibial prostheses and non-stemmed prostheses. RESULTS: All-cause revision for TKA with stem extension was higher for the first 6 months (hazard ratio [HR] 1.47; 95% confidence interval [CI]1.19 to 1.82; P < .001); while after 1.5 years TKA with stem extension had a lower rate of revision (HR 0.84; 95% CI 0.73 to 0.97; P = .01). Stemmed components were more likely to be revised for infection between 3 months and 1.5 years after surgery (HR 1.39; 95% CI 1.05 to 1.83; P = .02). The revision rate for aseptic loosening was lower in the stemmed group beyond 2 years (HR = 0.45; 95% CI 0.31 to 0.63; P < .001). Insert-only revision was higher in the stemmed group at all times (HR = 1.42; 95% CI 1.21 to 1.66, P < .001). Isolated tibial component revision was lower in the stemmed group at all times (HR 0.47; 95% CI 0.29 to 0.74; P = .001). Aseptic loosening for tibial component-only revision was significantly lower in the stemmed group at all times (HR 0.23; 95% CI 0.11 to 0.50; P < .001). CONCLUSIONS: Patients undergoing primary stemmed TKA have lower rates of all-cause revision beyond 1.5 years and tibial component-only revision at all times. Further investigation is required to preoperatively select patients that benefit from augmentation with stems.

Grief Training in Palliative Care Fellowships.

INTRODUCTION: No prior study has assessed grief and bereavement curriculum in Hospice and Palliative Medicine (HPM) fellowship programs in the United States. METHODS: A 14-item survey was created and distributed to Accreditation Council for Graduate Medical Education (ACGME)-accredited HPM fellowship Program Directors to assess program demographics, curriculum emphasis, grief and bereavement programming, and attitudes toward grief and bereavement training for HPM fellows. RESULTS: The overall survey response rate was 63%. Most palliative care programs were academic (74%) and had four or fewer fellows (85%). 90% devoted a minority (0%-10%) of their curriculum to grief and bereavement training. Most programs reported at least some program-led grief and bereavement programming (69%); however, 53% endorsed that fellows are not very or not at all involved in this programming. Almost half of programs only have a small amount of programming related to supporting families after loss (49%). The majority endorsed having a great deal of programming for debriefing or supporting fellows through professional grief (55%), and the most common modalities were debriefing sessions (62%) and ensuring access to mental health resources (41%). The most common ways of teaching grief and bereavement were through bedside/anecdotal teaching and lectures/case conferences. Most program directors felt that palliative care fellowships should provide grief and bereavement training (81%) and consider it important or very important for fellows to learn how to process grief and bereavement (92%). DISCUSSION: It was widely reported by program directors that grief and bereavement training are important curricular components for HPM fellows. Acknowledging professional grief remains an underrecognized need in palliative care training and practice. Our study suggests that for grief and bereavement curricula in HPM fellowships, the time dedicated, specific types, and amount of fellow involvement was highly variable. It will be critical for programs to disseminate best practices to help move toward a more uniform approach for ensuring basic competency in grief and bereavement training in HPM fellowship programs in the United States.