Citations

We report a case of a triazole and echinocandin-resistant C. glabrata right shoulder prosthetic joint infection in a 60-year-old woman. The patient underwent surgery and received the novel triterpenoid antifungal agent ibrexafungerp. She initially improved, but relapsed four months post-treatment. This case highlights the potential role of ibrexafungerp in multidrug-resistant Candida infections.

Background and purpose New Zealand White Rabbits are a useful preclinical model for neurovascular research. Inducing right common carotid artery aneurysms in New Zealand White Rabbits gives researchers the ability to test neurovascular devices in vivo. This study takes advantage of archived angiograms to obtain vascular measurements of interest for future research in rabbit models. Methods Rabbit angiograms from endovascular studies conducted in-house between 2005 and 2024 were analyzed using ImageJ at points of interest along the thoracic and abdominal aorta. Using scale references, the diameters of various New Zealand White Rabbit (2.5–3.5 kg) arteries were measured for aneurysm models and controls. Anatomic vascular variations were categorized and recorded. Results Measurable artery diameters at 39 points of interest were recorded for 170 female New Zealand White Rabbits. Type 1 vascular anatomy was the most common rabbit aortic arch, characterizing 85% of identifiable rabbit anatomies in this study. Conclusion By making these measurements available, this study simplifies future neurovascular studies, allowing for vasculature to be selected by size depending on the application. Additionally, the study offers insight into the relationship between elastase-induced aneurysms and surrounding vasculature size and draws size comparisons between some key arteries of interest.

Background: Supracondylar humerus fractures (SCH) are the most common type of elbow fracture in children, with many cases requiring surgery. Treatment of postoperative pain for SCH has high variability, but can often be treated effectively with minimal or no opioids. Furthermore, there is significant morbidity related to pediatric opioid consumption. The goal of this study was to characterize prescription patterns in the United States following closed reduction and percutaneous pinning (CRPP) of SCH. Methods: All patients aged 10 or younger years who underwent CRPP of SCH from January 2010 to December 2021 were identified in the PearlDiver Mariner Claims Database. The primary outcome was postoperative pain medication prescriptions in the 30 days following SCH CRPP. Patient demographics, prescription duration, and morphine milligram equivalents (MME) were analyzed. Multivariable-log-binomial mixed regression models were constructed to assess factors associated with increased opioid prescription. Results: In total, 43,611 SCH CRPP cases in patients aged 10 or younger were identified from 2010 to 2021. Throughout the study period, 48.6% of patients (21,191/43,611) received and filled a narcotic pain prescription. The percentage of patients receiving opioid medication decreased from 54.7% in 2010 to 27.4% in 2021. Opioid prescriptions totaled a mean of 6.1±2.1 days of narcotics with a mean of 79.2 MME prescribed per patient. Increased patient age, increased Elixhauser comorbidity index, and Medicaid insurance were all associated with increased opioid prescription (P<0.001). Living in the Northeast, increased family income, and commercial insurance were associated with decreased opioid prescriptions (P<0.001). Conclusions: Nearly half of the patients over the past decade treated with CRPP for SCH received a narcotic prescription. However, there has been a steady decline in the proportion of patients being prescribed opioids, with only 27.4% receiving opioids in 2021. Further, patients with increased comorbidities or those insured by Medicaid with lower mean family income may be at risk for increased opioid prescription. While efforts have been made to reduce opioid overprescribing, there continues to be room for further reduction in opioid utilization after CRPP for SCH moving forward.

Abstract Normal pressure hydrocephalus is typically defined by the triad of gait disturbance, cognitive impairment, and urinary incontinence, and is characterized on MRI by disproportionately enlarged subarachnoid-space. Gait disturbance is also a commonly reported symptom in Parkinsonian disorders, especially progressive supranuclear palsy, although the frequency, clinical significance and mechanisms of hydrocephalus in these disorders are unclear. We aimed to assess the prevalence of hydrocephalic MRI parameters in a large cohort of Parkinsonian disorders and evaluate associations with clinical features and abnormalities on MRI and PET. Two hundred and thirty-eight participants with a Parkinsonian disorder, including 181 progressive supranuclear palsy, 36 corticobasal syndrome and 21 Parkinson’s disease, were enrolled from Mayo Clinic by the Neurodegenerative Research Group between September 2009 to October 2023. Automated detection of disproportionately enlarged subarachnoid-space hydrocephalus (D) was applied and using Evans’ index (E) cut-off point &gt;0.3, participants were classified based on both measures as imaging-suggestive of hydrocephalus (D+E+), enlarged subarachnoid-space only (D+E−), large Evans’ index only (D−E+) and no imaging evidence of hydrocephalus (D−E−). Demographic, clinical and imaging features, including magnetic resonance parkinsonism index, cortical and subcortical volumes, white matter hyperintensities, diffusion tractography metrics, and metabolism on PET, were compared across groups. Among the 238 participants, 24 had borderline subarachnoid space scores and were excluded. The remaining 214 participants were classified as: D+E+ (n = 20, 9%); D+E− (n = 8, 4%); D−E+ (n = 71, 33%) and D−E− (n = 115, 54%). Among the progressive supranuclear palsy participants, 11% were D+E+, 4% D+E−, 34% D−E+ and 51% D−E−. Most cases (n = 18) in the imaging-suggestive of hydrocephalus D+E+ group had progressive supranuclear palsy. The D+E+ participants were older, had more disorientation, more downgaze palsy, greater midbrain and cortical atrophy, lower striatal metabolism, greater degeneration of long-range white matter tracts, larger cistern areas and more periventricular and deep white matter hyperintensities compared to the D−E− participants without imaging evidence of hydrocephalus. The D+E− participants had the highest metabolism in the paracentral lobule and superior parietal gyrus. The D−E+ participants showed worse disease severity and greater midbrain and cortical atrophy compared to the D−E− participants. These findings demonstrate that disproportionately enlarged subarachnoid-space hydrocephalus occurs in ∼15% of progressive supranuclear palsy participants, and is associated with worse clinical and imaging outcomes, as well as white matter hyperintensities. We hypothesize that disproportionately enlarged subarachnoid-space may be a mechanistic byproduct of degeneration and subsequent cerebrospinal fluid flow re-distribution in progressive supranuclear palsy.

PURPOSE Tumor treating fields (TTFields) use alternating electric fields to disrupt cancer cell proliferation. Feasibility of TTFields therapy with gemcitabine/nab-paclitaxel was previously demonstrated in patients with advanced pancreatic adenocarcinoma. PANOVA-3 was designed to confirm safety and efficacy of TTFields in patients with unresectable locally advanced pancreatic adenocarcinoma (LA-PAC). METHODS In this global phase III trial, 571 patients with newly diagnosed LA-PAC were randomly assigned to receive gemcitabine 1,000 mg/m 2 and nab-paclitaxel 125 mg/m 2 by intravenous infusion once a day on days 1, 8, and 15 of a 28-day cycle with or without TTFields. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), local PFS, pain-free survival, and overall response rate (ORR). Distant PFS was analyzed post hoc. RESULTS OS was significantly prolonged using TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel (median, 16.2 months [95% CI, 15.0 to 18.0] v 14.2 months [95% CI, 12.8 to 15.4]; hazard ratio [HR], 0.82 [95% CI, 0.68 to 0.99]; P = .039). PFS, local PFS, and ORR were not improved. Pain-free survival was significantly prolonged with TTFields with gemcitabine/nab-paclitaxel (median, 15.2 months [95% CI, 10.3 to 22.8] v 9.1 months [95% CI, 7.4 to 12.7]; HR, 0.74 [95% CI, 0.56 to 0.97]; P = .027), as was distant PFS (median, 13.9 months [95% CI, 12.2 to 16.8] v 11.5 months [95% CI, 10.4 to 12.9]; HR, 0.74 [95% CI, 0.57 to 0.96]; P = .022). Device-related skin adverse events (AEs) were experienced by 76.3% of patients. Most device-related skin AEs were mild to moderate, with 7.7% of patients reporting a grade 3 AE. CONCLUSION This study demonstrated significant OS, pain-free survival, and distant PFS benefits for TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in patients with unresectable LA-PAC, with no additive systemic toxicity.

ImportanceHip fractures present a substantial public health challenge, with projections of more than 500 000 per year by 2040. As such, frailty indices such as the Revised Risk Analysis Index (RAI) and the Modified Five-Item Frailty Index (mFI-5) have been recently investigated as metrics for preoperative risk stratification for these patients.ObjectiveTo understand the accuracy of frailty, as measured by the RAI and the mFI-5, for estimating 30-day mortality following surgically managed hip fractures.Design, Setting, and ParticipantsThis retrospective cross-sectional analysis used the American College of Surgeons’ National Surgical Quality Improvement database. Patients aged 65 years old with surgically managed traumatic hip fracture from 2015 to 2019 were included. Frailty was evaluated using the RAI, a 5-domain scale with 14 weighted variables graded from 0 to 81, and the mFI-5, a 2-domain scale with 5 unweighted variables graded from 0 to 5; for both, a higher score denotes worse frailty. Data collection occurred from May to June 2024.ExposureDiagnosis of hip fracture and undergoing surgical fixation, hemiarthroplasty, or total hip arthroplasty.Main Outcomes and MeasuresThe primary outcome was 30-day mortality. Multivariable regression was conducted to assess the estimating value of frailty scales. Discriminatory accuracy was assessed using a receiver operating characteristic curve and quantified using a C-statistic.ResultsThe cohort consisted of 114 359 patients (70 038 female [69.9%]; median [IQR] age, 84 [77-89] years) with 51 071 prefrail patients (44.7%) according to the mFI-5 and 31 883 very frail patients (27.9%) according to the RAI comprising the largest frailty groups. Increasing frailty status was associated with greater odds ratio (OR) for 30-day mortality for both the mFI-5 (prefrail OR, 1.35 [95% CI, 1.24-1.47]; frail OR, 2.11 [95% CI, 1.94-2.30]; severely frail OR, 3.53 [95% CI, 3.20-3.90]; P &amp;lt; .001 for all) and RAI (normal OR, 1.55 [95% CI, 1.35-1.79]; frail OR, 2.97 [95% CI, 2.59-3.42]; very frail OR, 6.17 [95% CI, 5.38-7.08]; P &amp;lt; .001 for all). The RAI demonstrated superior discriminatory accuracy for 30-day mortality compared with the mFI-5 (area under the receiver operating characteristic curve, 0.73 [95% CI, 0.72-0.73] vs 0.61 [95% CI, 0.60-0.62]; P &amp;lt; .001).Conclusions and RelevanceIn this cross-sectional study of 114 359 patients, the RAI demonstrated superior odds and discriminatory accuracy for estimating 30-day mortality following surgical management of hip fractures. The RAI may be considered as a risk stratification tool for orthopedic surgeons to adjunct surgical planning, thereby reducing postoperative mortality.

5108 Background: We previously proposed a hybrid framework combining LLMs and rule based algorithm (RBA) for automating risk stratification in locPCa. Herein, we aim to validate the risk stratification agent (RSA) in a prospective cohort, develop & evaluate the treatment recommendation agent (TRA) based on NCCN guidelines, and develop an interactive interface to facilitate clinicians for accurate risk stratification and treatment recommendations at the point of care. Methods: This study included pts with locPCa (2004-2024) presenting at Mayo Clinic with at least 1 positive prostate biopsy and MRI report available. For RSA prospective validation, GPT4 extracted key phenotypic variables (PSA, T stage, prostate volume, number of cores, Gleason patterns, grade group) from unstructured MRI and biopsy reports using a zeroshot prompt. An RBA then classified pts into NCCN risk groups. The agent performance was compared with the treating clinician's documentation and evaluated against gold-standard labels manually annotated by two independent clinicians. For development of TRA, two experiments were performed using GPT4 with and without retrieval-augmented generation (RAG) to generate treatment plans. Generated treatment plans were evaluated using NCCN guideline-informed treatment decision tree based algorithm (DTA). Evaluation metrics, weighted – accuracy (acc) and F1, were computed. A clinician facing interface (lisr.org/risk) was developed to provide accurate risk stratification and treatment plans. Results: A total of 858 pts were included (500 for prospective validation, 358 for treatment recommendations). Prospective validation for RSA demonstrated a higher F1 score of 0.89 compared to the treating clinician (F1: 0.58). Treatment recommendation experiments showed that GPT4 with RAG achieved higher acc (64% full – all correct treatment options and 36% partial – at least 1 correct treatment option) compared to GPT4 alone (35% and 65%, respectively). Sensitivity analysis using DTA-informed GPT4 note generation achieved 94% full acc and 6% partial acc. GPT4 alone generated hallucinated treatment options in 71% of cases, while GPT4 with RAG reduced this to 32%. Conclusions: The multi-agent framework based on LLM and RBA achieves high accuracy in risk stratification and treatment recommendation for locPCa. A multi-agent framework with an interactive interface holds high promise to enable efficient, accurate decision-making, and improve locPCa management at the point of care Performance evaluation. RSA(acc; F1) % TRA(full acc; partial acc) % Clinician RSA* GPT4 RAG+GPT4 DTA+GPT4 Overall 60; 58 89; 89 29; 71 64; 36 94; 6 V. High 94; 33 96; 96 55; 45 69; 31 93; 7 High 46; 52 92; 89 - - - Int. Unf 80; 61 91; 90 5; 95 38; 62 93; 7 Int. Fav 57; 64 84; 87 0; 100 98; 2 100; 0 Low 57; 65 87; 80 100; 0 95; 5 90; 10 V. Low 8; 13 50; 67^ - - - *Statistical significance (p<0.01) except for ^V. Low.

e17168 Background: Prostate cancer is the most prevalent cancer and the second leading cancer related death in men in the USA. Radical prostatectomy represents the mainstay treatment for patients with localized prostate cancer. Management of metastatic disease requires multidisciplinary practice and innovative approach for individualized favorable outcomes. Treatment sequencing in patients with advanced prostate cancer has been reported to impact patient’s response to subsequent treatment as well as overall survival outcomes. Here in, we thought to investigate the impact of prior chemotherapy treatment on PSA response rates to 177Lut PSMA. Methods: We conduct a single center retrospective study including 164 patients diagnosed with advanced prostate cancer and treated with 177Lut PSMA for metastatic hormone resistant prostate cancer. 92 patients received 177Lut PSMA as a salvage treatment late after chemotherapy (group A), and we compared them with 70 patients received 177Lut PSMA early in an adjuvant fashion within 3 months after chemotherapy (group B). Favorable PSA response was defined by 50% or more reduction in PSA value after complete treatment with 177Lut PSMA. Results: Approximately 43 % of patients in (group B) received their 177Lut PSMA within six months. The average number of chemo cycles received by patients of (group B) is between 3 to 6 cycles. Median patients’ age (IQR) 63 years (57.75 - 68), median (IQR) number of cycles of 177Lut PSMA 5 (5 - 6). Statistical analyses were performed to determine any differences in post lut PSA response in both groups of patients. Approximately 49 % of patients in (group A) had favorable PSA response versus 44 % of patients in (group B) (p-value 0.3853). Conclusions: The use of 177Lut-PSMA in the post-chemotherapy setting demonstrated similar outcomes whether administered early or late. These findings suggest that the timing of treatment may not significantly impact its effectiveness, but further research is needed to confirm these results and explore potential optimizations for patient care.

e17081 Background: Prostate cancer is the most common cancer in men. In early localized disease, surgery represents the mainstay treatment. However, management of metastatic and advanced stages requires multidisciplinary approach. The prognosis in metastatic prostate cancer has improved recently due to advanced pharmaceutical and interventional methods of treatment with modern diagnostic methods. In our study, we aim to investigate the impact of concomitant treatment with 2nd generation hormonal therapy and 177Lut PSMA on PSA response in patients with metastatic CRPC Methods: In a retrospective observation study including 91male patients with metastatic CRPC treated with 177Lut PSMA, we divided our cohort into 2 groups depending on whether they had 2nd generation hormonal therapy alongside their treatment with 177Lut PSMA. 43 patients received 177Lut PSMA (group A). While the other 48 patients (group B) had 2 nd generation hormone therapy with 177Lut PSMA. Primary endpoint was PSA response after they complete their therapy. Favorable PSA response was defined by PSA reduction more than 50% from baseline PSA before treatment Results: Statistical analysis identified 91 male patients, median (IQR) age of 61.5 years (56,67.75). Median (IQR) Gleason score 8 (7 - 9). Pre-177Lut PSMA PSA had a median of 2 (0.255 - 99), post-177Lut PSMA had a median of 0.15 (0.1 - 2.7). Median (IQR) 177Lut PSMA 6 (5 - 6). There was no significant change in PSA response in patients who received 177Lut PSMA alone versus 177Lut PSMA with concomitant 2 nd generation hormonal therapy. Of that, 54.17% of group B had favorable PSA response compared to 48.84% of group A (P value 0.6115). In multivariable analysis, concomitant treatment with 2nd generation hormone therapy and 177Lut PSMA has no impact on PSA response rates. Conclusions: This data suggests that concomitant treatment with 2nd generation therapy and 177Lut PSMA did not demonstrate superior PSA response than treatment with 177Lut PSMA alone. This data contributes to the current literature and serve in patients counseling. Further studies are warranted.

Abstract Introduction Emerging evidence suggests that positive airway pressure (PAP) treatment for moderate-to-severe obstructive sleep apnea (OSA) in elderly patients does not improve daytime sleepiness, or quality of life outcomes, despite improving apnea-hypopnea index (AHI). While oral appliance therapy (OAT) is known to be an effective treatment for mild-to-moderate OSA, its efficacy in treatment of elderly patients with severe OSA is unknown. Methods Retrospective chart review of patients ≥ 65 years old with diagnosis of OSA, treated with OAT, who underwent subsequent follow-up sleep testing and clinical assessments, including Epworth Sleepiness Scale (ESS), a measure of daytime sleepiness. Results We studied 66 elderly patients with OSA (31 women, 35 men), including 58 with mild-to-moderate OSA (AHI &lt; 30) and 8 with severe OSA (AHI ≥ 30) treated with OAT. At baseline, patients with mild-to-moderate OSA had a median AHI of 11.6 compared to 41.3 in patients with severe OSA (p &lt; 0.0001). There was no difference in ESS score between patients with mild-to-moderate OSA (median ESS = 8; IQR = 4-12) and severe OSA (median ESS = 6; IQR = 3-9). Following their OSA diagnosis, OAT was offered due to PAP intolerance (n = 32), patient preference (n = 28), or as an alternative treatment option (n = 4). After initiation of OAT, 42 patients with mild-to-moderate and 7 with severe OSA underwent follow-up assessment with home sleep testing (n = 32), oximetry (n = 15), or polysomnography (n = 2). At follow-up assessment, ESS was decreased in patients with mild-to-moderate OSA (median ESS = 5; IQR = 3-8) and severe OSA (median ESS = 5; IQR = 3-7), indicating reduction in daytime sleepiness in response to OAT in both groups. Moreover, 50% of patients with mild-to-moderate OSA and 50% of severe OSA patients saw ≥ 50% reduction in AHI. Conclusion Our study findings suggest that treatment with OAT in mild-to-moderate and severe OSA is tolerable and effective in elderly patients who do not have contraindication for this treatment. OAT should be considered as an alternative treatment specifically for elderly adults with severe OSA not tolerating or improving with PAP therapy. Support (if any)