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Background Resilience refers to the ability to adapt or recover from stress. There is increasing appreciation that it plays an important role in wholistic patient-centered care and may affect patient outcomes, including those of orthopaedic surgery. Despite being a focus of the current orthopaedic evidence, there is no strong understanding yet of whether resilience is a stable patient quality or a dynamic one that may be modified perioperatively to improve patient-reported outcome scores. Questions/purposes (1) Does resilience change postoperatively? (2) How do outcome measures change postoperatively in relation to resilience grouping? (3) For patients who do have resilience instability (change in resilience of ≥ 1 SD between any two follow-up points), how were patient-level factors, surgical characteristics, and outcome measures associated with instability? Methods In this single-surgeon, retrospective, comparative study, we identified all patients who underwent shoulder surgery between March 2021 and March 2023 from the medical records of one US military teaching hospital, resulting in 144 initial patients. Data on resilience (measured by the Brief Resilience Scale) and outcomes (assessed using the Numeric Rating Scale [NRS] and the Single Assessment Numeric Evaluation [SANE]) were collected for all patients and maintained in a longitudinal outcomes score database. Patients younger than 18 years of age (1% [1 of 144]) who underwent surgery for fracture, acute tendon rupture (8% [11 of 144]), or revision surgery (3% [4 of 144]); had concomitant shoulder conditions (such as, instability or rotator cuff tear) (1% [2 of 144]); or had incomplete follow-up data (4% [5 of 144]) were excluded, leaving 84% (121 of 144) of the original sample size for analysis. Among the patients, 12% (15 of 121) were women, the mean age was 41 ± 15 years, and the most common indication for surgery was instability (40% [48 of 121]) followed by rotator cuff repair (29% [35 of 121]). Based on their preoperative Brief Resilience Scale and its deviation from the mean, patients were stratified into low (> 1 SD below mean), intermediate (within 1 SD above and below mean), and high (> 1 SD above mean) resilience groups. Preoperatively, 19% (23 of 121) of patients were classified as low resilience, 62% (75 of 121) as intermediate resilience, and 19% (23 of 121) as high resilience. The mean ± SD preoperative Brief Resilience Scale score was 25 ± 4. The Brief Resilience Scale is a six-item scale with a calculated summary score ranging from 6 to 30. A higher score is suggestive of greater perceived resilience. There were no differences in the preoperative Brief Resilience Scale score with regard to age, gender, type of surgery performed, or outcome measures. Patient resilience was followed during the postoperative period for a minimum of 6 months, and instability in the scale was evaluated. Instability in resilience was defined as change in Brief Resilience Scale score by > 1 SD from one follow-up time point to another. Perioperative NRS and SANE outcomes, in addition to demographic data, were utilized to evaluate the relationship between resilience and patient-level factors. Results Brief Resilience Scale groups across all time points remained consistent with no change in grouping or crossover in groups except for patients with low resilience who had an increase in mean ± SD Brief Resilience Scale score by the final follow-up (18 ± 3 versus 20 ± 4; p < 0.05). Regardless of resilience group, there was a decrease in mean ± SD NRS (4.4 ± 2.2 versus 2.4 ± 2.3; p < 0.001) and an improvement in mean ± SD SANE (46 ± 19 versus 69 ± 21; p < 0.001) scores during the postoperative period. At the 1- to 2-month follow-up and the 6- to 10-month follow-up visits, patients with high resilience were more likely to have lower NRS scores than patients with intermediate resilience (1.8 ± 1.0 versus 3.8 ± 2.3; p = 0.003) and low resilience (1.5 ± 1.8 versus 3.3 ± 2.4; p < 0.001), respectively. No relationship was observed between resilience groups and SANE scores, surgical category, and percentage of patients meeting the minimum clinically important difference (MCID) of the NRS or the SANE. Regarding resilience instability, 46% (56 of 121) of patients were categorized as having a Brief Resilience Scale change of ≥ 1 SD from baseline during the postoperative period. Gender (r = 0.03; p = 0.21), age (p = 0.81), and surgical category (r = 0.01; p = 0.88) were not associated with the likelihood of resilience instability. Individuals whose resilience increased had a lower starting Brief Resilience Scale score than those whose resilience stayed the same (22 ± 4 versus 25 ± 4, respectively; p < 0.001) or those whose resilience decreased (22 ± 4 versus 26 ± 3, respectively; p < 0.001). Conclusion When evaluated by resilience group, the trait appears static; however, at the individual level, resilience appears dynamic and complex. Patients with high resilience may have less postoperative pain. Identification of patients with low resilience may indicate patients who experience more dynamic change in this psychometric property. Level of Evidence Level III, therapeutic study.

Background Bacteremia is sometimes observed in patients with prosthetic joint infection (PJI), and it is associated with a lower likelihood of infection control. However, the prevalence and association of bacteremia in chronic PJI remain unknown. Questions/purposes (1) What percentage of patients are diagnosed with bacteremia at the time of hospital admission and before surgery for chronic PJI? (2) What clinical factors are associated with positive blood cultures? (3) To what degree are positive blood cultures associated with infection-free implant survival in patients with chronic PJI? Methods This prospective study was conducted at a single academic institution from June 2021 to August 2022. Within the study period, we treated 124 patients for chronic PJI, defined according to the modified Musculoskeletal Infection Society (MSIS) criteria. Of those, we considered patients who underwent revision surgery because of chronic PJI of the hip or knee as potentially eligible. All patients received two blood cultures within 48 hours after admission but before surgery. The second blood culture was performed on the contralateral arm 1 hour after the first was completed. Based on that, 87% (108 of 124) of patients were eligible; 13% (16 of 124) were excluded because of delayed blood sample transfers in 6% (7 of 124) of patients, contaminated samples in 2% (2 of 124), late hematogenous infection in 2% (3 of 124), and antibiotic use within 2 weeks before sampling in 3% (4 of 124). No patients were lost before the minimum study follow-up of 2 years without having reached a study endpoint (reinfection or persistent PJI) or had incomplete datasets, leaving 74% (92 of 124) for analysis here. The median (range) time from the index surgery (previous primary, debridement, or revision procedure) to the current revision for PJI in these patients was 16 months (2 to 180). Of the included patients, 40% (37 of 92) were men, 39% (36 of 92) had PJI of the hip, and 61% (56 of 92) had PJI of the knee. The mean age of patients was 65 ± 13 years, and the mean BMI was 28 ± 3 kg/m2. The interval between two cultures was at least 1 hour, and one culture was taken from each of the patient’s arms. Patients were divided into blood culture–positive and blood culture–negative groups based on preoperative blood culture results. The chi-square test and the independent t-test were used to compare demographic characteristics (gender, age, BMI, and affected joint) and clinical factors (American Society of Anesthesiologists [ASA] classification, hematological tests, comorbidities) between the two groups. Further multivariable logistic regression analysis was performed to assess the factors associated with positive blood cultures, which controlled for potential confounders including age, gender, BMI, and affected joint. The Firth penalized likelihood was employed when there was monotone likelihood in logistic regression analysis to reduce small-sample bias. A Kaplan-Meier curve tracked infection-free implant survival over 30 months, with differences evaluated using the log-rank test. Results Overall, 15% (14 of 92) of patients had positive blood cultures. After adjusting for age, gender, infection site, BMI, and intraoperative isolation of gram-positive cocci, we found that patients classified as ASA III (OR 4 [95% confidence interval (CI) 1 to 21]; p = 0.04) and those who had diabetes (OR 14 [95% CI 3 to 100]; p < 0.001) had a higher odds of positive blood cultures. We found no difference in the Kaplan-Meier estimate for infection-free implant survival at 30 months between those with positive blood cultures (86% [95% CI 76% to 95%]) and those with negative blood cultures (91% [95% CI 88% to 94%]; p = 0.51). Conclusion In this prospective, observational study, we found that chronic PJI can potentially lead to hematogenous dissemination of pathogens, particularly in patients with poor overall health (such as those classified as ASA III and patients diagnosed with diabetes). Therefore, selective preoperative blood cultures may be crucial in helping clinicians implement early intervention measures to prevent the serious consequences of bacteremia in patients with poor baseline health and those with other implanted devices. Larger studies with longer follow-up are needed to further validate these findings, ensure more robust estimates, and conduct comprehensive evaluations of the risk factors associated with positive blood cultures in chronic PJI. Level of Evidence Level II, therapeutic study.

ABSTRACT Background Existing risk scores assessing geriatric vulnerability in the emergency department (ED) have shown limited predictive power, especially in diverse populations. We investigated the relationship of a quick and easy‐to‐administer geriatric vulnerability scoring system with functional decline and mortality in older patients admitted to multiple hospitals through the ED in the United States (US) and Brazil (BR). Method Federated, international, multicenter observational study of hospitalized ED patients aged ≥ 65 from US and BR. The six criteria from the PRO‐AGE score (Physical impairment, Recent hospitalization, Older age [≥ 90], Acute mental alteration, Getting thinner, and Exhaustion; 0–8; higher scores = greater vulnerability) were assessed on admission. We used proportional hazards models to investigate the relationships between PRO‐AGE score groups and 90‐day mortality and functional decline, defined as new dependence in activities of daily living (ADL) and instrumental ADL (IADL), after adjusting for age, sex, race and ethnicity, education, Charlson comorbidity score, and study site. Death was considered a competing event for the functional decline outcome. Results A total of 1390 patients were included (US = 560; Brazil = 830). The 90‐day risk of death was higher for the upper compared with the lower (reference) PRO‐AGE group in both cohorts (US: HR = 11.76; 95% confidence interval [CI] = 2.56–54.04; BR: HR = 12.29; 95% CI = 3.54–42.59), whereas the risk of new 90‐day ADL disability was higher for upper (HR = 2.08; 95% CI = 1.21–3.56) and middle groups (HR = 2.10; 95% CI = 1.35–3.27) in the US but only the upper group in BR (HR = 1.70; 95% CI = 1.02–2.85). Conclusion A higher PRO‐AGE score was associated with mortality and functional decline in older ED patients admitted to hospitals in the US and BR, demonstrating its generalizability as a geriatric vulnerability risk score.

Abstract Translational large-animal models that can accommodate human-scale implantable devices are essential for advancing neuromodulation therapies in epilepsy. This study establishes a kainic acid (KA)-induced porcine model of mesial temporal lobe epilepsy (mTLE) using clinical imaging, stereotactic surgery, and a fully implantable neural stimulation and recording (INSR) device designed for humans. Seven pigs (six KA-treated and one saline control) underwent MRI-guided stereotactic implantation of electrodes targeting bilateral hippocampus (HPC) and anterior thalamus (ANT), followed by intra-hippocampal KA or saline infusion. Local field potentials (LFP) were recorded continuously with synchronized video monitoring. Seizures and LFP interictal epileptiform-like discharges (IEDs) were quantified using validated automated detectors. Histology was performed in the saline control and the longest surviving KA-treated pig. Intra-hippocampal KA infusion induced acute status epilepticus in all (6/6) treated pigs. Four animals survived to chronic monitoring with spontaneous seizures observed in three pigs (2,733 seizures; mean duration of 27.2 ± 17.6 seconds). IEDs were observed in bilateral HPC of all animals, including saline control, with higher rates in the lesioned HPC (p <0.0001). While the IED morphology is consistent with epileptiform activity; IEDs alone are not specific for epilepsy and physiological transients (e.g. sharp-wave ripples) and injury-related hyperexcitability or strain-specific hyperexcitability cannot be excluded. Histological analysis revealed patchy neuronal loss and cytoarchitectural changes in HPC. This porcine model reproduces electrophysiological features of human mTLE. This approach provides a powerful translational bridge for developing and testing next-generation INSR and neuromodulation strategies in freely behaving large animals.

ImportanceChronic obstructive pulmonary disease (COPD) is often undiagnosed. Although genetic risk plays a significant role in COPD susceptibility, its utility in guiding spirometry testing and identifying undiagnosed cases is unclear.ObjectiveTo determine whether a COPD polygenic risk score (PRS) enhances the identification of undiagnosed COPD beyond a case-finding questionnaire (eg, the Lung Function Questionnaire) using conventional risk factors and respiratory symptoms.Design, Setting, and ParticipantsThis cross-sectional analysis of participants 35 years or older who reported no history of physician-diagnosed COPD was conducted using data from 2 observational studies: the community-based Framingham Heart Study (FHS) and the COPD-enriched Genetic Epidemiology of COPD (COPDGene) study.ExposuresModified Lung Function Questionnaire (mLFQ) scores and COPD PRS.Main Outcomes and MeasuresThe primary outcome was spirometry-defined moderate to severe COPD (forced expiratory volume in the first second of expiration/forced vital capacity [FEV1/FVC] &amp;lt;0.7 and FEV1 [percent predicted] &amp;lt;80%). The performance of logistic models was assessed using the PRS, mLFQ score, and PRS plus mLFQ score for predicting spirometry-defined COPD.ResultsAmong 3385 FHS participants (median age, 52.0 years; 45.9% male) and 4095 COPDGene participants (median age, 56.8 years; 55.5% male) who reported no history of COPD, 160 (4.7%) FHS and 775 (18.9%) COPDGene participants had spirometry-defined COPD. Adding the PRS to the mLFQ score significantly improved the area under the curve from 0.78 to 0.84 (P &amp;lt; .001) in FHS, 0.69 to 0.72 (P = .04) in COPDGene non-Hispanic African American, and 0.75 to 0.78 (P &amp;lt; .001) in COPDGene non-Hispanic White participants. At a risk threshold for spirometry referral of 10%, the addition of the PRS to the mLFQ score correctly reclassified 13.8% (95% CI, 6.6%-21.0%) of COPD cases in FHS, but not in COPDGene.Conclusions and RelevanceA COPD PRS enhances the identification of undiagnosed COPD beyond a conventional case-finding approach in the general population. Further research is needed to assess its impact on COPD diagnosis and outcomes.

Purpose: Trabecular micro-bypass devices (TBDs) such as the iStent series (Glaukos Corporation), are effective in reducing intraocular pressure (IOP). However, precise placement of TBDs is crucial in achieving surgical efficacy, as device malpositioning may lead to suboptimal IOP reduction. We demonstrate 2 novel intraoperative signs to aid confirmation of accurate iStent placement, without reliance on imaging technologies. Methods: Surgical technique report with video accompaniment. Surgical Technique: Two intraoperative clinical signs that confirm optimal iStent placement are described: (1) Luminal Blood Reflux—achieved by gently decompressing the anterior chamber, with or without flushing of the stent lumen with balanced salt solution (BSS), thereby confirming stent positioning in the Schlemm canal (SC). (2) Schlemm’s Bidirectional Fluid Wave (SBFW)—observable when flushing with BSS, suggesting fluid movement in the canal segments adjacent to the iStent device, thereby confirming stent patency and positioning in the SC. Conclusion: The identified signs are useful, feasible, and reproducible indicators of accurate iStent placement. Future studies may evaluate the application of these confirmatory maneuvers in diverse clinical contexts and further establish a correlation with clinical outcomes.

PURPOSE Over 50% of households in the United States have at least one musician—many musicians are also breast cancer survivors. This group has not been well studied, and given the level of fine sensory-motor skill required for musicianship, we hypothesized that musicians experience unique manifestations of breast cancer treatment toxicities. METHODS A nine-item Musical Toxicity Questionnaire (MTQ) was distributed to patients who had consented to participate in the Mayo Clinic Breast Cancer Registry. The MTQ screened participants by asking if they played a musical instrument or sang in the last 10 years: questions populated for those who answered yes. Respondents were asked if they noticed difficulty with their musical endeavor during or after breast cancer treatment, defined as acute musical toxicity (AMT). The questionnaire asked which side effect and cancer-directed therapy most influenced musical ability, what musical attributes were affected, and the timeline of resolution. Multivariable and classification tree analyses assessed relationships between AMT and treatment characteristics. RESULTS Of 1,871 survey respondents, 29% (535/1,871) self-identified as musicians. Over a quarter (27%, 144/535) reported AMT, and for 57% (82/144), AMT had not resolved at the time of survey. Of the treatments each participant received, chemotherapy was most often reported as most negatively impactful (63/89 who received chemotherapy, 71%). Decreased endurance was the most common musical difficulty (64% of those with AMT, 92/144), followed by decreased accuracy, trouble playing/singing quickly, and difficulty using proper technique. Multivariable and classification tree analyses revealed that receipt of chemotherapy was most strongly correlated with AMT. CONCLUSION These results will help oncology care teams counsel musicians, answer questions about impacts on musicality, and provide a timeline for resolution of musical symptoms.

ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by clinicians and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and 2 (online only) for more . PURPOSE To provide updated guidance regarding neoadjuvant chemotherapy (NACT) and primary cytoreductive surgery (PCS) among patients with stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer (epithelial ovarian cancer [EOC]). METHODS A multidisciplinary Expert Panel convened and updated the systematic review. RESULTS Sixty-one studies form the evidence base. RECOMMENDATIONS Patients with suspected stage III-IV EOC should be evaluated by a gynecologic oncologist, with cancer antigen 125, computed tomography of the abdomen and pelvis, and chest imaging included. All patients with EOC should be offered germline genetic and somatic testing at diagnosis. For patients with newly diagnosed advanced EOC who are fit for surgery and have a high likelihood of achieving complete cytoreduction, PCS is recommended. For patients fit for PCS but deemed unlikely to have complete cytoreduction, NACT is recommended. Patients with newly diagnosed advanced EOC and a high perioperative risk profile should receive NACT. Before NACT, patients should have histologic confirmation of invasive ovarian cancer. For NACT, a platinum-taxane doublet is recommended. Interval cytoreductive surgery (ICS) should be performed after ≤four cycles of NACT for patients with a response to chemotherapy or stable disease. For patients with stage III disease, good performance status, and adequate renal function treated with NACT, hyperthermic intraperitoneal chemotherapy may be offered during ICS. After ICS, chemotherapy should continue to complete a six-cycle treatment plan with the optional addition of bevacizumab. Patients with EOC should be offered US Food and Drug Administration–approved maintenance treatments. Patients with progressive disease on NACT should have diagnosis reconfirmed via tissue biopsy. Patients without previous comprehensive genetic or molecular profiling should be offered testing. Treatment options include alternative chemotherapy regimens, clinical trials, and/or initiation of end-of-life care. Additional information is available at www.asco.org/gynecologic-cancer-guidelines . This guideline has been endorsed by the Society of Gynecologic Oncology.

Abstract Background The underlying cause of fever of unknown origin (FUO) remains unidentified in up to 51% of cases despite systematic evaluation. Microbial cell-free DNA next-generation sequencing (mcfDNA-NGS) offers an agnostic, noninvasive approach to pathogen identification, but the utility and clinical impact of this assay in FUO remain unknown. Methods This retrospective cohort study evaluated adult patients referred for FUO evaluation at a tertiary medical center between November 2019 and November 2023. Patients underwent both standard microbiologic testing (ST) and mcfDNA-NGS. Diagnostic impact was assessed in 4 domains: new diagnoses, earlier time to diagnosis, avoidance of invasive procedures, and non-hypothesis-driven diagnoses. Logistic regression was used to identify predictors of positive mcfDNA-NGS testing. Results Among 176 patients, mcfDNA-NGS was positive in 44.3%, with 49% of these cases considered clinically significant. Infectious cause of FUO was identified in 39% of patients, noninfectious in 35%, and unknown in 26%. mcfDNA-NGS contributed to a positive diagnostic impact in 30% of cases, mainly by earlier diagnosis (16%) and potential for avoidance of invasive procedures (10%). Positive mcfDNA-NGS was significantly associated with higher Charlson comorbidity index score (odds ratio [OR], 1.22; P &lt; .001) and white blood cell (WBC) count ≤4.5 × 109 cells/L (OR, 8.61; P &lt; .001). Conversely, FUO without localization was associated with a decreased likelihood of positive mcfNDA testing (OR, 0.18; P &lt; .001). Conclusions mcfDNA-NGS effectively complements ST in diagnosing FUO, providing earlier detection and minimizing invasive testing. Clinical predictors such as high comorbidity and low WBC count may guide the optimal use of mcfDNA-NGS in FUO. Prospective evaluation of optimal timing and use of mcfDNA-NGS and cost-benefit analysis in FUO is needed.