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ABSTRACTObjectiveClinical outcome measures for autoimmune encephalitis (AE) are not yet well defined. Cognitive outcome measures (CogOs) and patient‐reported outcomes (PROs) may capture the symptoms of AE, beyond clinician‐reported outcomes (ClinROs) (the Modified Rankin Scale [mRS] and Clinical Assessment Scale in Autoimmune Encephalitis [CASE]).MethodsThis retrospective cohort study examined LGI‐1‐IgG AE patients at Cleveland Clinic. CogOs included the Rey Auditory Verbal Learning Test (RAVLT) and Brief Visuospatial Memory Test (BVMT). PROs included Neuro‐QoL, PROMIS Global Physical (GPH) and Mental Health (GMH). Abnormal RAVLT, BVMT (≤ −1.5 SD), Neuro‐QoL, and PROMIS (≥ 10 T‐scores) proportions were analyzed. CogOs and PROs were correlated with ClinROs using Spearman's rank correlation.ResultsForty‐four patients (64% male, mean age 68 [SD = 11], median follow‐up 19 months) were included. ClinROs improved, with median mRS decreasing from 2.5 (IQR = 2–3) to 2 (IQR = 1–2), and CASE from 5 (IQR = 3–6) to 3 (IQR = 2–3) (all p < 0.05). RAVLT (n = 15), BVMT (n = 16), Neuro‐QoL (n = 21), and PROMIS (n = 34) were available. At > 12 months from diagnosis, cognition was impaired on BVMT (56%) and RAVLT (20%). PROs showed impairments in Neuro‐QoL lower (38%) and upper (27%) extremity function, cognition (31%), and PROMIS‐GPH (25%). RAVLT correlated with Neuro‐QoL cognition, depression, and stigma, while BVMT correlated with PROMIS‐GMH (all unadjusted p < 0.05). Neither RAVLT nor BVMT correlated with ClinROs. ClinROs correlated with Neuro‐QoL lower extremity function, cognition, and social roles (all p < 0.05).InterpretationLGI‐1‐IgG AE patients have long‐term impairments in cognition, physical health, and social roles, which can be objectively measured using CogOs and PROs and are not captured by ClinROs.

Background/Objective: Noninvasive PET imaging-based assessment of PD-L1 expression is of high clinical value for better patient selection and treatment response rates to PD-L1 immunotherapies. Due to their shorter biological half-life and faster clearance from the blood pool, radiolabeled antibody fragments are an attractive alternative for imaging than their full-length IgG counterpart. This work investigated the radiosynthesis and in vitro cell uptake of anti-PD-L1-B11-nanobody radiolabeled with 44Sc (t1/2 = 4.04 h) as an alternative to anti-PD-L1-B11-IgG, better suited for longer half-life radioisotopes such as 89Zr (t1/2 = 78.41 h). Methods: The proteins were conjugated with p-SCN-Bn-DTPA and radiolabeled at room temperature with 44Sc, achieving a radiochemical yield of a RCY of 94.8 ± 3.1% (n = 3) for [44Sc]Sc-B11-IgG and 73.6 ± 12.1% (n = 3) for [44Sc]Sc-B11-nanobody, before purification. Results: Significantly higher uptake in the PD-L1+ cells than PD-L1KO cells was observed for both probes. However, high non-specific uptake, particularly of the radiolabeled B11-nanobody, was also observed which may negatively impact its potential as a molecular imaging probe. Conclusions: Due to the high non-specific uptake in vitro, the 44Sc radiolabeled nanobody was not progressed to further in vivo evaluation. These results should, however, not discourage future evaluations of other nanobody based probes radiolabeled with 44Sc, due to their well-matched biological and physical half-life.

Abstract Organoids, which are tiny, lab-grown 3D structures that mimic some organizational and functional properties of human organs, are slowly transforming the face of systems and developmental biology, biomedical research, pharmaceutical testing, environmental toxin testing, and healthcare. Significant investments are essential for the mass production, preservation, and distribution of organoids, with the aim to accelerate innovation and progress across multiple fields—much like the investments made in cell and biologics manufacturing over the past 2 decades.

Abstract Sinonasal cancers are malignant neoplasms arising from the nasal cavity and paranasal sinuses, including squamous cell carcinoma (SCC), adenocarcinoma, and undifferentiated carcinoma. Due to their rarity, comprehensive genomic data remain limited. Treatments include surgery, radiation, and chemotherapy, with ongoing trials investigating agents like cetuximab, cisplatin, and Tazemetostat. We analyzed sinonasal cancer cases from the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database via cBioPortal (v16.1-public, accessed July 22, 2024). Common gene mutations, correlations, and mutual exclusivities were assessed using statistical analyses with false discovery rate correction. Of 2,595 head and neck cancer samples, 122 (4.7%) were sinonasal carcinoma: 70 (57.4%) SCC, 31 (25.4%) undifferentiated carcinoma, and 21 (17.2%) adenocarcinomas. The most frequent mutations were TP53 (tumor protein 53; 40%), PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; 14%), KMT2D (lysine methyltransferase 2D; 11%), and CDKN2A (cyclin-dependent kinase inhibitor 2A; 9%). Subtype-specific mutations included IDH2 (isocitrate dehydrogenase; 230%) in undifferentiated carcinoma and FAT1 (15%) in adenocarcinoma. TP53 frequently co-occurred with PRKDC (protein kinase, DNA-activated, catalytic subunit; p = 0.020), while KMT2D co-occurred with PIK3CA (p = 0.018). TP53, PIK3CA, and KMT2D mutations are prevalent in sinonasal carcinoma, highlighting potential targets for therapy. Tazemetostat, targeting KMT2D-related DNA (deoxyribonucleic acid) methylation, and cetuximab, targeting the PIK3CA signaling cascade, may offer therapeutic benefits. Further research on mutation-specific therapies could improve treatment strategies.

Abstract Olfactory neuroblastoma (ONB) is a rare head and neck cancer arising from the upper nasal cavity, with limited systemic therapeutic options due to a poor understanding of its genomic landscape. This study aims to utilize a patient-level genomic repository to identify potential therapeutic targets and improve disease modeling in ONB. Retrospective genomic analysis. Data analysis was performed using the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database. Patients with confirmed ONB who have undergone targeted sequencing within GENIE. Data were analyzed for recurrent somatic mutations, along with their clinical and demographic correlations, with significance set at p < 0.05. A high prevalence of mutations in TP53 (tumor protein p53) and FRK (fibroblast growth factor receptor kinase) genes was identified. A moderate prevalence of mutations in NOTCH3 (notch receptor 3), SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4), RET (rearranged during transfection), and CTCF (CCCTC-binding factor) was also identified. The mutation patterns differed between pediatric and adult ONB cases. Specific mutations were enriched in metastatic tumors compared with primary tumors. This study provides a genomic profile for ONB, identifying key mutations and potential therapeutic targets. The identification of frequently mutated genes like TP53 and FRK suggests potential targets for novel therapies. The observation that certain genes are mutated in pediatric ONB but not adult ONB (and vice versa), and the presence of specific mutations in metastatic tumors that are absent in primary tumors, offers valuable insights for future precision medicine and the design of targeted therapeutic interventions for these distinct clinical presentations.

Aims Testicular sex cord‐stromal tumours (TSCSTs) are relatively rare, accounting for ~5% of all testicular neoplasms. They were historically classified into Leydig cell tumour, Sertoli cell tumour, granulosa cell tumour, and unclassified sex cord‐stromal tumour. More recently, classification was expanded to incorporate additional histologic types, including some associated with inherited cancer predisposition syndromes. However, the classification of TSCSTs still relies entirely on morphology, with some tumour types being defined based on their resemblance to ovarian counterparts. In recent years, molecular studies have identified drivers and genomic alterations associated with aggressive behaviour and progression; however, these findings have not yet impacted classification and management. Methods and results Under sponsorship of the International Society of Urological Pathology (ISUP) and the Genitourinary Pathology Society (GUPS), a group of genitourinary pathologists was assembled in 2023 with the aim of assessing how to use these new data to improve the classification and management of TSCSTs. Conclusions This paper summarizes the recommendations derived from the consensus activities and the first meeting of the te sticular s ex cord‐ s tromal t umour (TESST) group (held at Johns Hopkins Hospital, Baltimore, USA, 3/23/2024).

We assessed associations of pediatrician demographic characteristics with patient satisfaction (PS) scores. We performed a retrospective analysis of PS scores among pediatricians at a single academic institution and their associations with individual demographic features including gender, race, and geographic location of medical school education. We analyzed PS survey results for 153 pediatricians, 48.4% of whom were female. Males received higher scores in 4 out of 10 questions including “Likelihood of your recommending this care provider to others” ( P = .007). We observed similar findings for white pediatricians compared to Black, Indigenous, and People of Color (BIPOC) ( P = .033) and US medical school graduates compared to international school graduates ( P = .044). Overall, we observed that pediatricians who are female, BIPOC, or international medical school graduates receive lower PS scores than their counterparts. The impact of potential survey responder bias should be acknowledged when interpreting PS scores for pediatricians.

SummaryThe goal of this study was to ascertain the effect of patient body size on clinic‐ or patient‐delayed health care during the COVID‐19 pandemic and factors predicting delay. Primary survey data were collected in August 2021 from 3593 individuals living within the communities near Mayo Clinic facilities in Minnesota, Wisconsin, Arizona, and Florida. More people who identified with the higher‐weight BMI categories reported having their care appointments cancelled (62.3%) compared to those who identified with normative weight (38.0%) or underweight (47.7%; p < .001) and reported more frequently delaying their own care (67.9%) relative to those who identified with normative weight (47.0%) or underweight (62.3%; p < .001). Higher‐weight people were more likely than others to report delay was due to not knowing where to get care (UW: 5.6%, NW: 3.5%, HW: 7.0%, pchi‐square < .001), worrying about weight‐based judgement (UW: 2.1%, NW: 2.1%, HW: 4.5%, pchi‐square < .001), and fearing discrimination (UW: 2.9%, NW: 2.4%, HW: 5.5%, pchi‐square < .001). There was no difference across groups in delay due to fear of COVID‐19 exposure. Weight gain was associated with care delay in higher‐weight and normative weight groups. Having experienced more patient‐centred care pre‐COVID was associated with less care delay in the normative weight group, but more care delay in other groups. Higher‐weight people were more likely to have their care delayed by health care providers and to delay care themselves. Patient weight gain and concerns about discrimination and judgement about weight gain may have driven the delay of needed care during COVID‐19.

Background: Periacetabular osteotomy (PAO) is a complex procedure historically requiring inpatient stay. However, there is increased emphasis for other complex orthopaedic procedures (eg, arthroplasty) to be performed on an outpatient basis by insurance companies. Increasing resistance to insurance approval of inpatient listing for PAO patients at the participating institution suggests that this changing tide is affecting PAO surgery. Purpose: To (1) investigate the proportion of PAOs various surgical listing classifications (outpatient, outpatient-overnight, inpatient, etc), (2) determine the incidence of subsequent denial/request for additional documentation for approval of inpatient stay after PAO, and (3) characterize the accuracy of preoperative patient listing classification as well as mean length of stay (LOS) and incidence of successful same-day discharge after PAO at a single institution. Study Design: Case series; Level of evidence, 3. Methods: A retrospective chart review was performed to identify all PAOs, performed by 4 participating surgeons, at a single academic institution over a 2-year period. The initial listing status as an outpatient-overnight or inpatient procedure was identified. Whether a preoperative peer review was required for approval of inpatient listings as well as if additional documentation was necessary to convert outpatient-overnight listings to inpatient stays were also recorded. Results: A total of 140 PAOs among 117 patients were performed with 25 (17.9%) initially listed as an inpatient stay and 115 (82.1%) listed as outpatient-overnight. Of the 25 PAOs listed as inpatient, 2 (8.0%) required a preoperative peer review process to justify or clarify listing status. The mean LOS was 1.9 ± 1.4 days with 55.7% (78/140) of PAOs staying ≥2 nights in the hospital. Only 6 PAOs (4.3%) went home the same day as surgery. Patients who underwent PAO with concomitant hip arthroscopy stayed on average 2.4 ± 1.2 days in comparison with 1.6 ± 1.4 days for those who underwent PAO alone ( P < .001). Of the 115 PAOs listed as an outpatient-overnight, 53 (46.1%) converted to an inpatient stay, all of which required service documentation to support conversion to inpatient status. Conclusion: Over half of PAOs performed resulted in an inpatient stay with patients spending ≥2 nights in the hospital. Additionally, all conversions from outpatient-overnight to inpatient required additional service documentation to support status conversion. Understanding trends in postoperative hospitalizations and LOS may allow for better informed partnerships between surgeons and insurance companies creating more efficient preauthorizations, billing practices, and expected patterns of patient care and discharge.

TPS2689 Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, existing FDA approved companion diagnostic biomarkers like PD-L1, dMMR/MSI-H and TMB have low accuracy in predicting response. Ex vivo cytokine profiling of live tumor samples has shown promise as an improved means of predicting response to PD-1 blockade (Voabil, et al. Nat Med. 2021), but this approach has been limited to tumor resections given the need for large amounts of tissue. Here we present three clinical trials that leverage a novel approach using limited tissue from a single core needle biopsy (CNB) (20 gauge or larger). A sequential ex vivo treatment strategy is used, eliminating the need for a separate control arm and addressing challenges with tumor heterogeneity, particularly in CNBs where tissue is limiting. Using a specialized instrument, CNBs are cut into live tumor fragments (LTFs) which are viable in culture and retain the native tumor microenvironment, enabling cytokine profiling in response to ICI treatment ex vivo. Methods: ELEPHAS-01 (NCT05478538), ELEPHAS-02 (NCT05520099) and ELEPHAS-04 (NCT06349642) are observational prospective clinical trials initiated to characterize the accuracy of this approach for predicting ICI response. Over 750 patients that are being considered for standard of care (SOC) ICI therapy in the metastatic/relapse or neoadjuvant setting will be enrolled (Table). Fresh live CNBs are collected prior to treatment start and processed within 24 hrs enabling prediction of results within 72 hrs of receipt. LTFs are treated using a strategy where control (IgG) and SOC ICI treatments are performed sequentially on the same tissue in a single well. Changes in the cytokine secretion rates are then compared between ICI and control to characterize immunotherapy response. Additionally, tissue viability and tumor content measurements are used to assess tissue quality. Clinical response is measured using pathologic response in patients receiving neoadjuvant ICI therapy, while RECIST v1.1 is used in all other patients. The primary objective of these trials is to determine the platform’s ex vivo accuracy (e.g., sensitivity, specificity) for predicting clinical response to ICIs and comparing it to the accuracy of PD-L1, dMMR/MSI-H and TMB. Clinical trial information: NCT06349642 , NCT05478538 , NCT05520099 . ELEPHAS-01 (Lung) ELEPHAS-02 (Hoosier) ELEPHAS-04 (Mayo) Setting Metastatic & recurrent Metastatic & recurrent Metastatic, recurrent & neoadjuvant Tumor type Lung Bladder, kidney, colorectal, head and neck, lung, melanoma, endometrial Metastatic/recurrent: lung, skin, esophageal, cervical, endometrial, colon, liver, kidney, bladder Neoadjuvant: breast–TNBC, lung Enrollment as of 1/27/2025 26 44 20 Est. total enrollment 216 216 324 Clinical endpoints RECIST v1.1 RECIST v1.1 RECIST v1.1 & Pathologic response at surgery