Citations

Bronchial-subarachnoid fistulas are rare occurrences, which are not well defined in the literature. This uncommon clinical phenomenon may result in symptomatic pneumorrhachis and presents unique clinical challenges. This report details a case of a 53-year-old female whose treatment for recurrent chondrosarcoma of the thoracic spine included multiple surgeries and radiotherapy. Two weeks after her most recent debulking surgery, she experienced a rapid onset of unusual symptoms, including headache, back and neck spasms, bladder incontinence, and confusion. The source of her symptoms was found to be secondary to pneumorrhachis from a pre-existing bronchial-pleural fistula that had fistulized to the subarachnoid space discovered on computed tomography (CT) and confirmed intraoperatively. The patient was treated successfully with high-flow oxygen therapy and bed rest, followed by surgical correction of both a pleural air leak and a dural defect with muscular flaps. The patient was discharged home in stable condition and remained clinically free of recurrent bronchial-subarachnoid fistula six months after surgical repair. This case contributes to the existing literature by providing detailed clinical insights into the diagnosis and successful management of a bronchial-subarachnoid fistula leading to pneumorrhachis, thereby highlighting the importance of early recognition and intervention and underscoring the need for further research in this area.

Most patients with metastatic prostate cancer eventually develop resistance to primary androgen deprivation therapy. To identify predictive biomarker for Abiraterone acetate/prednisone resistance, we screened alternative splice variants between responders and non-responders from the PROMOTE clinical study and pinned down the most significant variant, CENPK–delta8. Through preclinical patient-derived mouse xenograft (PDX) and 3D organoids obtained from responders and non-responders, as well as in vitro models, aberrant CENPK–delta8 expression was determined to link to drug resistance via enhanced migration and proliferation. The FLNA and FLOT1 were observed to specifically bind to CENK–delta8 rather than wild-type CENPK, underscoring the role of CENPK–delta8 in cytoskeleton organization and cell migration. Our study, leveraging data from the PROMOTE study, TCGA, and TCGA SpliceReq databases, highlights the important function of alternative splice variants in drug response and their potential to be prognostic biomarkers for improving individual therapeutic outcomes in precision medicine.

Abstract Aims Radiation therapy (RT) is an integral component of cancer therapy but associated with adverse events. Our goal was to establish risk prediction models for major adverse cardiovascular and cerebrovascular events (MACCE) after chest RT. Methods and results A retrospective study of lung/breast cancer patients who had chest RT with planning CT at Mayo Clinic between 01/2010 and 01/2014. Predictive models were developed based on weighted independent predictors using a derivation (406 lung and 711 breast cancer) and validation cohort (179 lung and 234 breast cancer). Patient characteristics, pre-RT CT for coronary artery calcification (CAC), and post-RT MACCE data were reviewed. Post-RT MACCE occurred in 6.1 and 5.6% in the derivation and validation cohort over a mean follow-up of 42 ± 13 months. Post-therapy model (C2AD2) included CAC (two points), MACCE history (two points), age ≥74 (three points), DM (two points), and mean heart radiation dose ≥ 850 mGy (two points), and pre-therapy model (C2AD) included post-therapy model parameters minus mean heart radiation dose. Both models stratified patients into three risk groups: low (0–2), intermediate (3–5), and high (≥6). Post-RT MACCE across these groups were 2.7, 8.9, and 19.8% in the derivation, and 3.9, 6.6, and 16.4% in the validation cohort for post-therapy model (C2AD2) and 2.8, 9.2, and 20.4% in the derivation and 3.7, 9.2, and 13.2% in the validation cohort for pre-therapy model. Both models showed statistically significant graded survival outcome. Conclusion Post-therapy (C2AD2) and pre-therapy (C2AD) models are simple, easy to use and effective tools to stratify breast and lung cancer patients undergoing chest radiation for post-RT MACCE.

Context.— Generative artificial intelligence (AI) technologies are rapidly transforming numerous fields, including pathology, and hold significant potential to revolutionize educational approaches. Objective.— To explore the application of generative AI, particularly large language models and multimodal tools, for enhancing pathology education. We describe their potential to create personalized learning experiences, streamline content development, expand access to educational resources, and support both learners and educators throughout the training and practice continuum. Data Sources.— We draw on insights from existing literature on AI in education and the collective expertise of the coauthors within this rapidly evolving field. Case studies highlight practical applications of large language models, demonstrating both the potential benefits and unique challenges associated with implementing these technologies in pathology education. Conclusions.— Generative AI presents a powerful tool kit for enriching pathology education, offering opportunities for greater engagement, accessibility, and personalization. Careful consideration of ethical implications, potential risks, and appropriate mitigation strategies is essential for the responsible and effective integration of these technologies. Future success lies in fostering collaborative development between AI experts and medical educators, prioritizing ongoing human oversight and transparency to ensure that generative AI augments, rather than supplants, the vital role of educators in pathology training and practice.

ABSTRACTBackgroundFollowing breast cancer (BC), many young women are interested in future childbearing and some may wish to breastfeed. However, limited information is available regarding their lactation experiences.MethodsParticipants in the Young Women's Breast Cancer Study, a multicenter, prospective cohort study of women ≤40 years diagnosed with stage 0–III BC between 2006–2016 and who reported one or more live births following diagnosis, were surveyed about pregnancy and breastfeeding after BC treatment, including reasons for attempting and stopping breastfeeding, satisfaction, and supports.ResultsOf 143 eligible women sent a survey, 115 responded and 94 were included in the analytic cohort. Breastfeeding was attempted by 55% of women (52 of 94). Among those who had not attempted, 93% noted prior bilateral mastectomies (39 of 42). Among those who attempted breastfeeding, 69% had undergone lumpectomy and radiotherapy (36 of 52), 83% of whom reported no milk production from their treated breast (30 of 36). Most (65%, 34 of 52) were at least somewhat satisfied with their ability to breastfeed. Reasons for stopping breastfeeding included: having completed the planned duration (36%, 19 of 52); to start/resume endocrine therapy (21%, 11 of 52); and to resume breast imaging (8%, 4 of 52). Approximately half (27 of 55) of women who had not undergone bilateral mastectomies recalled receiving specific information about breastfeeding after BC, mostly from the oncology team (59%, 16 of 27), online resources (48%, 13 of 27), or a lactation consultant (44%, 12 of 27).ConclusionMost young BC survivors who attempted to breastfeed were able to and were satisfied with the experience, despite challenges. Specific resources to support BC survivors who wish to breastfeed are needed.

Background In this open-label, randomized, non-comparative, multicenter phase II study (Alliance A091401) we report on three expansion cohorts treated with nivolumab (N) with and without ipilimumab (N+I) and provide a multi-omic correlative analysis of actionable biomarkers. Methods Patients were randomized (non-comparative) to receive either N or N+I. The primary endpoint was a 6-month confirmed response rate (CRR) defined by Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included treatment-related adverse events (TRAEs), progression-free survival, and overall survival. Multi-omic correlative analyses were conducted using samples from both the primary and expansion cohorts. Results A total of 66 patients were evaluated for the primary endpoint with disease including gastrointestinal stromal tumor (GIST, n=18), undifferentiated pleomorphic sarcoma (UPS, n=24), and dedifferentiated liposarcoma (DDLPS, n=24). Neither N nor N+I achieved a complete or partial response in the GIST expansion cohort. In DDLPS and UPS, the primary response endpoint of CRR was met with N+I (both 16.6%, 2/12) but not with N alone (both 8.3%, 1/12). In the GIST cohort, TRAE was higher with N+I treatment, halting enrollment as required per protocol. In a correlative analysis of patients for the expansion cohort and the original cohort (n=86), traditional biomarkers of immunotherapy response were not correlated with response in any histological subtype. Markers of genomic instability including the presence of gene fusions and increased subclonal mutations correlated with improved clinical outcomes. Conclusions This expansion cohort reaffirms the outcomes of A091401. There remains a pressing need to determine the role of and predictive biomarkers for immunotherapy in sarcoma. Trial registration number NCT02500797.