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Context.— The diagnosis and characterization of well-differentiated neuroendocrine tumors (WDNETs) on cytology is challenging, with recognized pitfalls that may have therapeutic and prognostic implications. Objective.— To analyze data curated by the College of American Pathologists educational slide program for accuracy in the cytologic diagnosis of WDNET. The current state of cytologic diagnosis of WDNET is also reviewed for educational purposes. Design.— The study cohort included non-gynecologic cytology slides reviewed by participants in the College of American Pathologists Non-Gynecologic Cytopathology Education program. Individual responses for cytotechnologists or cytologists (CT) and pathologists were collated for WDNET. The data were analyzed for concordance with the correct general diagnosis and concordance with the correct reference diagnosis. The exact reference diagnosis available for each site was “pancreatic neuroendocrine tumor,” “liver, well/moderately differentiated neuroendocrine tumor,” and “lung, well/moderately differentiated neuroendocrine tumor.” Performance measures were assessed. Results.— The WDNET analysis includes 8941 responses from 1382 laboratories. The selection of the general diagnosis of “malignant” or “suspicious for malignancy” was greater than 90% in all body sites. Pathologists correctly identifying WDNET was highest in the pancreas (2501/2738, 91.3%) compared with the lung (805/1019, 79.0%) and liver (1444/1966, 73.4%). Pathologists had better concordance with the diagnosis of WDNET in all sites than CTs ( P < .001). Conclusions.— This large study, encompassing pathologists and CTs, confirms that although participants can identify WDNET on cytology, opportunities for greater accuracy and education persist. The most common incorrect response in the pancreas was adenocarcinoma, while the most common misdiagnosis was small cell carcinoma in the lung and liver.

Importance Ischemia-reperfusion injury contributes to graft dysfunction after liver transplant. Hypothermic oxygenated perfusion (HOPE) has been shown to improve liver function, but its benefit in extended criteria donors in a US population remains unclear. Objective To assess whether back-to-base portal-venous HOPE impacts outcomes after liver transplant in the US. Design, Setting, and Participants The Bridge to HOPE Trial is a multicenter, randomized, open-label trial with 1-year follow-up. The study took place at 15 US liver transplant centers and patients were enrolled between January 2021 and May 2023. Central assessment of complications and cholangiograms for nonanastomotic biliary strictures (NAS) was blinded to treatment arm. Participants included 219 recipients of extended-criteria donor livers after brain death (DBD) and after circulatory death (DCD) who were randomized 1:1 to HOPE after static cold storage (SCS) (n = 109) or SCS only (n = 110). Randomization was performed after liver inspection and acceptance for transplant. Data were analyzed from December 2024 to July 2025. Intervention After SCS and transport, livers underwent portal-venous HOPE until implant, using the VitaSmart HOPE System. Main Outcomes and Measures The primary efficacy end point was early allograft dysfunction (EAD). Other main outcomes included model for early allograft function (MEAF) score, hospital length of stay (LOS), patient and graft survival, and biliary complications. Additional post hoc analyses were performed. Results Overall, 219 patients (82 female [37.4%] and 137 male[62.6%]) were included (DCD, 57 of 219 [26%]) with 97% (212 of 219) completing 12-month follow-up. EAD incidence was 20.2% (22 of 109) with HOPE vs 37.3% (41 of 110) with SCS (rate difference, −17.1%; 95% CI, −27.2 to −7.0; noninferiority P &amp;lt; .001; superiority P = .005). HOPE treatment led to significantly lower MEAF mean (SD) scores (HOPE group, 4.28 [1.75]; control group, 4.82 [1.85]; mean difference, −0.54; 95% CI, −1.02 to −0.06; P = .03) and shorter median LOS (hazard ratio, 1.32; 95% CI, 1.01-1.73; P = .04). NAS on imaging and 1-year survivals were comparable between groups (patients: HOPE group, 106 of 109 [97.2%] vs SCS, 106 of 110 [96.4%]; graft: HOPE group, 104 of 109 [95.4%] vs SCS, 102 of 110 [92.7%]). Post hoc analyses showed numerically less graft loss due to NAS after HOPE (4 vs 1) and less major complications (Clavien-Dindo classification ≥IIIa) per patient, respectively. Conclusions and Relevance Back-to-base portal-venous HOPE was compared with SCS alone for extended risk DBD and DCD livers. The HOPE approach was safe and associated with reduced EAD, MEAF score, and LOS. These findings support the use of HOPE as a pragmatic strategy to improve early posttransplant outcomes. Trial Registration ClinicalTrials.gov Identifier: NCT05045794 .

Abstract We evaluated outcomes by management type for patients with stage IA nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) in the Global NLPHL One Working Group retrospective database of 2243 patients with stages I to IV disease diagnosed from 1992 to 2021 at 38 international institutions. A total of 779 patients had stage IA disease with median age of 35 years (range, 3-89) and median follow-up of 6.1 years. The 6-year progression-free survival (PFS) and overall survival were 86.3% and 97.7%, respectively. Outcomes were analyzed for the 2 groups: complete resection and unresected disease. Patients with a complete resection and observation alone (n = 99) had a 6-year PFS of 65.5% vs 90.5% for those who received radiotherapy (RT) (n = 53). Patients with unresected disease (n = 627; 80.5%) had a 6-year PFS of 62.0% for rituximab alone (n = 31), 89.6% for RT alone (n = 325), 76.8% for ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) alone (n = 40), and 94.3% for ABVD plus RT (n = 130). A total of 127 patients relapsed (16.3%), of which 25 (19.7%) had transformation. Our analysis suggests the following: (1) RT improves the PFS in patients with completely resected disease; (2) rituximab or ABVD alone does not appear to achieve a durable response; and (3) chemotherapy was not observed to add additional PFS benefit when used in combination with RT. Thus, for stage IA NLPHL, RT alone is likely sufficient for definitive treatment.

Abstract INTRODUCTION Guidelines recommend non-surgical biopsy for indeterminate pulmonary lesions &gt; 8 mm. Shape-sensing robotic-assisted bronchoscopy (ssRAB) is growing in use to biopsy small pulmonary nodules; however current literature is limited to single center studies with limited follow-up. This study, PRECIsE, assessed safety and performance of the first ssRAB iteration across multiple sites and nascent users. METHODS Prospective, multicenter, observational study evaluating ssRAB without cone-beam CT guidance in patients with nodules 10–30 mm located in or beyond the sub-segmental airways. Patients were followed for 2 years; the primary endpoint was sensitivity for malignancy with diagnostic yield, and safety as secondary endpoints. Multilevel logistic regression models were used to control for factors associated with sensitivity and diagnostic yield. RESULTS A total of 305 procedures were performed across 6 centers. Median nodule size was 17.0 mm (IQR: 14.0–23.0) with bronchus sign present in 37% of cases. Sensitivity for malignancy through 2 years was 81.3% (95% CI: 75.7, 86.1). Multi-level modelling demonstrated female sex, smaller nodule size, lower lobe location, semi-solid density, and higher body-mass-index were associated with lower sensitivity. Diagnostic yield was 74.1% (95% CI: 68.8, 78.9) according to the ATS/ACCP criteria and 77.5% [95% CI: 72.4, 81.8] according to the intermediate criteria. Multi-level modeling demonstrated a non-significant site/center level effect on ATS/ACCP diagnostic yield (P = .36). Pneumothorax requiring intervention was 1.6% (5/305); bleeding was 1.0% (3/305) with two (2) Nashville grade 2 and one (1) Nashville grade 3 events. CONCLUSIONS The first iteration of ssRAB demonstrated encouraging performance and a strong safety profile among nascent users for the biopsy of small peripheral nodules.

Study Design. Modified Delphi consensus process Objective. To establish a standardized, consensus-driven definition for postoperative spine infection (PSI) for research, diagnosis, and management. Summary of Background Data. Postoperative infection is a devastating and common complication following spine surgery. Rates of PSI in the literature range from 0% to over 20% depending on surgical indication and invasiveness. Despite the implications of PSI, there is no universally accepted diagnostic standard or consensus definition for infection following spine surgery, hindering research and treatment of this challenging clinical condition. Methods. A multispecialty workgroup convened by the Musculoskeletal Infection Society (MSIS) conducted a systematic literature review. Using data from the systematic review, an expert panel completed a modified Delphi process to achieve consensus. The panel included nine fellowship-trained, board-certified physicians with expertise in infectious diseases, orthopaedic and neurologic spine surgery, and musculoskeletal radiology. Iterative rounds focused on criterion selection, importance ranking, categorical grouping, and final constellation development for PSI diagnosis. Consensus was defined as a 2/3 majority, with a target of 100%. Results. The workgroup achieved 100% consensus on a new PSI definition, which incorporates six clinical domains: wound features, microbiology, imaging, inflammatory biomarkers, intraoperative findings, and histology. A single microbiological stand-alone criterion—identification of a phenotypically indistinguishable organism from two or more deep operative site specimens—was established as pathognomonic for postoperative spine infection. Additional primary and secondary supporting criteria were defined, with specific combinations required to classify cases as definite or probable PSI. Final definitions were ratified by the boards of MSIS and the European Bone & Joint Infection Society (EBJIS) Conclusion. This consensus-based definition provides a standardized framework for diagnosing postoperative spine infection, facilitating research and clinical management. The criteria balance sensitivity and specificity across diverse clinical scenarios and represent the first multispecialty, society-endorsed definition for PSI.

Context.— Though numerous quality assurance (QA) measures are in place for the practice of gynecologic cytopathology, many of them are not clearly defined and may be variably used by laboratories worldwide. Objective.— To assess current practice patterns regarding the implementation of selected gynecologic cytology QA metrics to help develop guidance for laboratories. Design.— A supplemental questionnaire was mailed to laboratories participating in the 2022 College of American Pathologists (CAP) Gynecologic Cytopathology (PAP Education) Program requesting data regarding their QA measures in gynecologic cytology. Results.— A total of 562 laboratories responded to the supplemental questionnaire; responses from 511 laboratories were analyzed further. Of 492 laboratories, most considered Papanicolaou (Pap) tests from patients with untreated abnormal cytology in the previous year (386; 78.5%) or with an abnormal gynecologic biopsy finding (concurrent or within the past year) (331; 67.3%) as high-risk for negative rescreening. Many laboratories (436 of 511; 85.3%) required pathologist review of Pap tests for indications other than reactive/abnormal cells (eg, endometrial cells in women 45 years of age and older). For assessing cytologists’ performance, 88.5% (399 of 451) of respondents recorded the discrepancy rate between cytologist’s and pathologist’s interpretations. For monitoring pathologists’ performance, most laboratories (243 of 389; 62.5%) evaluated cases with significant cytologic-histologic discrepancy. Conclusions.— The CAP survey provided a detailed assessment of current QA practices regarding gynecologic cytology, which can aid laboratories in making decisions related to enhancement of QA in their setting. As the guidelines and tools for cervical cancer screening evolve, QA metrics will need to be accordingly refined.

Importance The modified Japanese Orthopaedic Association (mJOA) scale is the most common scale used to represent outcomes of degenerative cervical myelopathy (DCM); however, it lacks consideration for neck pain scores and neglects the multidimensional aspect of recovery after surgery. Objective To use a global statistical approach that incorporates assessments of multiple outcomes to reassess the efficacy of riluzole in patients undergoing spinal surgery for DCM. Design, Setting, and Participants This was a secondary analysis of prespecified secondary end points within the Efficacy of Riluzole in Surgical Treatment for Cervical Spondylotic Myelopathy (CSM-PROTECT) trial, a multicenter, double-blind, phase 3 randomized clinical trial conducted from January 2012 to May 2017. Adult surgical patients with DCM with moderate to severe myelopathy (mJOA scale score of 8-14) were randomized to receive either riluzole or placebo. The present study was conducted from July to December 2023. Intervention Riluzole (50 mg twice daily) or placebo for a total of 6 weeks, including 2 weeks prior to surgery and 4 weeks following surgery. Main Outcomes and Measures The primary outcome measure was a difference in clinical improvement from baseline to 1-year follow-up, assessed using a global statistical test (GST). The 36-Item Short Form Health Survey Physical Component Score (SF-36 PCS), arm and neck pain numeric rating scale (NRS) scores, American Spinal Injury Association (ASIA) motor score, and Nurick grade were combined into a single summary statistic known as the global treatment effect (GTE). Results Overall, 290 patients (riluzole group, 141; placebo group, 149; mean [SD] age, 59 [10.1] years; 161 [56%] male) were included. Riluzole showed a significantly higher probability of global improvement compared with placebo at 1-year follow-up (GTE, 0.08; 95% CI, 0.00-0.16; P = .02). A similar favorable global response was seen at 35 days and 6 months (GTE for both, 0.07; 95% CI, −0.01 to 0.15; P = .04), although the results were not statistically significant. Riluzole-treated patients had at least a 54% likelihood of achieving better outcomes at 1 year compared with the placebo group. The ASIA motor score and neck and arm pain NRS combination at 1 year provided the best-fit parsimonious model for detecting a benefit of riluzole (GTE, 0.11; 95% CI, 0.02-0.16; P = .007). Conclusions and Relevance In this secondary analysis of the CSM-PROTECT trial using a global outcome technique, riluzole was associated with improved clinical outcomes in patients with DCM. The GST offered probability-based results capable of representing diverse outcome scales and should be considered in future studies assessing spine surgery outcomes.

Study Design. Retrospective cohort study of prospectively accrued data. Objective. To evaluate a large, prospective, multicentre dataset of surgically treated degenerative cervical myelopathy (DCM) cases on the contemporary risk of C5 palsy with surgical approach. Summary of Background Data. The influence of surgical technique on postoperative C5 palsy after decompression for DCM is intensely debated. Comprehensive, covariate-adjusted analyses are needed using contemporary data. Methods. Patients with moderate to severe DCM were prospectively enrolled in the multicenter, randomized, Phase III CSM-Protect clinical trial and underwent either anterior or posterior decompression between Jan 31, 2012 and May 16, 2017. The primary outcome was the incidence of postoperative C5 palsy, defined as the onset of muscle weakness by at least one grade in manual muscle test at the C5 myotome with slight or absent sensory disruption after cervical surgery. Two comparative cohorts were made based on the anterior or posterior surgical approach. Multivariate hierarchical mixed-effects logistic regression was used to estimate odds ratios (OR) with 95% confidence intervals (CI) for C5 palsy. Results. A total of 283 patients were included, and 53.4% underwent posterior decompression. The total incidence of postoperative C5 palsy was 7.4% and was significantly higher in patients who underwent posterior decompression compared with anterior decompression (11.26% vs. 3.03%, P=0.008). After multivariable regression, the posterior approach was independently associated with greater than four times the likelihood of postoperative C5 palsy (P=0.017). Rates of C5 palsy recovery were comparable between the two surgical approaches. Conclusion. The odds of postoperative C5 palsy are significantly higher after posterior decompression compared to anterior decompression for DCM. This may influence surgical decision-making when there is equipoise in deciding between anterior and posterior treatment options for DCM. Level of Evidence. Therapeutic Level—II

PURPOSE Nodular lymphocyte–predominant Hodgkin lymphoma (NLPHL) is a rare cancer, and large international cooperative efforts are needed to evaluate the significance of clinical risk factors and immunoarchitectural patterns (IAPs) for all stages of pediatric and adult patients with NLPHL. METHODS Thirty-eight institutions participated in the Global nLPHL One Working Group retrospective study of NLPHL cases from 1992 to 2021. We measured progression-free survival (PFS), overall survival (OS), transformation rate, and lymphoma-specific death rate. We performed uni- and multivariable (MVA) Cox regression stratified by management to select factors for the lymphocyte-predominant international prognostic score (LP-IPS) validated by five-fold cross-validation. RESULTS We identified 2,243 patients with a median age of 37 years (IQR, 23-51). The median follow-up was 6.3 years (IQR, 3.4-10.8). Most had stage I to II (72.9%) and few B symptoms (9.9%) or splenic involvement (5.4%). IAP was scored for 916 (40.8%). Frontline management included chemotherapy alone (32.4%), combined modality therapy (30.5%), radiotherapy alone (24.0%), observation after excision (4.6%), rituximab alone (4.0%), active surveillance (3.4%), and rituximab and radiotherapy (1.1%). The PFS, OS, transformation, and lymphoma-specific death rates at 10 years were 70.8%, 91.6%, 4.8%, and 3.3%, respectively. On MVA, IAPs were not associated with PFS or OS, but IAP E had higher risk of transformation (hazard ratio [HR], 1.81; P < .05). We developed the LP-IPS with 1 point each for age ≥45 years, stage III-IV, hemoglobin <10.5 g/dL, and splenic involvement. Increasing LP-IPS was significantly associated with worse PFS (HR, 1.52) and OS (HR, 2.31) and increased risk of lymphoma-specific death (HR, 2.63) and transformation (HR, 1.41). CONCLUSION In this comprehensive study of all ages of patients with NLPHL, we develop the LP-IPS to identify high-risk patients and inform upcoming prospective clinical trials evaluating de-escalation of therapy for patients with low LP-IPS scores (<2).

Importance Oncocytic (Hürthle cell) thyroid carcinoma is a follicular cell-derived neoplasm that accounts for approximately 5% of all thyroid cancers. Until recently, it was categorized as a follicular thyroid carcinoma, and its management was standardized with that of other differentiated thyroid carcinomas. In 2022, given an improved understanding of the unique molecular profile and clinical behavior of oncocytic thyroid carcinoma, the World Health Organization reclassified oncocytic thyroid carcinoma as distinct from follicular thyroid carcinoma. The International Thyroid Oncology Group and the American Head and Neck Society then collaborated to review the existing evidence on oncocytic thyroid carcinoma, from diagnosis through clinical management and follow-up surveillance. Observations Given that oncocytic thyroid carcinoma was previously classified as a subtype of follicular thyroid carcinoma, it was clinically studied in that context. However, due to its low prevalence and previous classification schema, there are few studies that have specifically evaluated oncocytic thyroid carcinoma. Recent data indicate that oncocytic thyroid carcinoma is a distinct class of malignant thyroid tumor with a group of distinct genetic alterations and clinicopathologic features. Oncocytic thyroid carcinoma displays higher rates of somatic gene variants and genomic chromosomal loss of heterozygosity than do other thyroid cancers, and it harbors unique mitochondrial DNA variations. Clinically, oncocytic thyroid carcinoma is more likely to have locoregional (lymph node) metastases than is follicular thyroid carcinoma—with which it was formerly classified—and it develops distant metastases more frequently than papillary thyroid carcinoma. In addition, oncocytic thyroid carcinoma rarely absorbs radioiodine. Conclusions and Relevance The findings of this review suggest that the distinct clinical presentation of oncocytic thyroid carcinoma, including its metastatic behavior and its reduced avidity to radioiodine therapy, warrants a tailored disease management approach. The reclassification of oncocytic thyroid carcinoma by the World Health Organization is an important milestone toward developing a specific and comprehensive clinical management for oncocytic thyroid carcinoma that considers its distinct characteristics.