Citations

Abstract Pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive forms of pancreatic cancer, is associated with poor survival outcomes and currently ranks as the third leading cause of cancer-related death in the United States. Despite its clinical significance, the mechanisms of PDAC development and progression remain, in part, poorly understood. In this study, we provide evidence of a novel role of sorting nexin 10 (SNX10), a member of the sorting nexin family, in the regulation of KRAS-induced pancreatic carcinogenesis. We demonstrate that SNX10 is downregulated in PDAC, especially in advanced cases. Furthermore, mutational analysis revealed SNX10 genetic alterations in PDAC cases. Functional studies demonstrated that SNX10 overexpression in human PDAC cells inhibited cell proliferation and colony formation. Moreover, SNX10 overexpression induced G1-phase cell-cycle arrest and decreased KRAS signaling activity. Using a novel Snx10 knockout mouse crossed with a Kras-driven PDAC model, we observed reduced survival, increased tumor cell proliferation, enhanced aggression, and heightened inflammation. Collectively, these findings highlight SNX10 as a tumor suppressor candidate in PDAC and underscore its promise as a foundation for new therapeutic approaches. Significance: SNX10 plays a crucial role in reducing pancreatic tumorigenesis. This discovery offers valuable insights into PDAC’s biology and the development of new effective treatments.

BACKGROUND: Hemorrhoidal disease and immunosuppression are prevalent. Management of hemorrhoidal disease in this patient population is challenging. Most societies recommend conservative management due to the presumed risks of morbid complications, including sepsis and impaired healing. Data on the risks of office-based and operative procedures in immunocompromised patients are scant. OBJECTIVE: To evaluate postoperative outcomes after both office-based procedures and operative intervention for hemorrhoidal disease in immunocompromised patients. DESIGN: Retrospective medical record review. SETTINGS: Single-center, tertiary referral center. PATIENTS: Adult patients were included who had hemorrhoidal disease and primarily medication-induced immunosuppression and were undergoing an office-based procedure or operative intervention for hemorrhoidal disease while on immunosuppression at Mayo Clinic in Rochester between 2010 and 2023. MAIN OUTCOME MEASURES: The primary outcome was the development of infectious complications or wound complications. RESULTS: Fifty-five immunocompromised patients, with a median age of 60 years, underwent a total of 68 hemorrhoidal procedures during the study time frame. All patients had immunosuppression induced by medication, except for 1 patient with bone marrow failure syndrome. The most common reason for immunosuppression was rheumatoid arthritis, followed by prior kidney transplant. The most common medications were chronic corticosteroids and methotrexate in more than one-third of patients each. Of 68 total interventions, hemorrhoidectomy (32%) and excision of a thrombosed hemorrhoid (26%) were the 2 most common operations performed. Sixteen adverse events were reported in 14 patients (25%). Three cases of postoperative cellulitis were documented after thrombosed external hemorrhoid excision, hemorrhoidopexy, and Whitehead hemorrhoidectomy. No postoperative intravenous antibiotics were administered. No cases of pelvic sepsis were documented. LIMITATIONS: The retrospective nature of the study and the heterogeneity of the study population. CONCLUSIONS: These data suggest that office-based and surgical procedures are safe and feasible in patients with immunosuppression. See Video Abstract . SEGURIDAD DE LOS PROCEDIMIENTOS PARA EL TRATAMIENTO DE HEMORROIDES EN PACIENTES INMUNODEPRIMIDOS: LA EXPERIENCIA DE LA CLÍNICA MAYO ANTECEDENTES: La enfermedad hemorroidal y la inmunosupresión son prevalentes. El tratamiento de la enfermedad hemorroidal en esta población de pacientes es difícil. La mayoría de las sociedades recomiendan un tratamiento conservador debido a los riesgos presuntos de complicaciones mórbidas, como sepsis y alteración de la cicatrización. Los datos sobre los riesgos de los procedimientos ambulatorios y quirúrgicos en pacientes inmunodeprimidos son escasos. OBJETIVO: Evaluar los resultados posoperatorios tras procedimientos ambulatorios y cirugía para la enfermedad hemorroidal en pacientes inmunodeprimidos. DISEÑO: Revisión retrospectiva de historias clínicas. ENTORNO: Centro terciario de referencia único. PACIENTES: Pacientes adultos con enfermedad hemorroidal e inmunosupresión inducida principalmente por medicamentos que se sometieron a un procedimiento ambulatorio o a una intervención quirúrgica para la enfermedad hemorroidal mientras estaban en tratamiento inmunosupresor en la Clínica Mayo de Rochester entre 2010 y 2023. PPRINCIPALES MEDIDAS DE RESULTADO: El resultado principal fue la aparición de complicaciones infecciosas o complicaciones de la herida. RESULTADOS: Cincuenta y cinco pacientes inmunodeprimidos, con una mediana de edad de 60 años, se sometieron a un total de 68 procedimientos hemorroidales durante el periodo de estudio. Todos los pacientes presentaban inmunosupresión inducida por medicación, excepto uno con síndrome de insuficiencia medular. La causa más frecuente de inmunosupresión fue la artritis reumatoide, seguida de un trasplante renal previo. Los medicamentos más frecuentes fueron los corticosteroides crónicos y el metotrexato, en más de un tercio de los pacientes. De las 68 intervenciones totales, la hemorroidectomía (32 %) y la extirpación de una hemorroide trombosada (26 %) fueron las dos operaciones más comunes realizadas. Se notificaron 16 eventos adversos en 14 (25 %) pacientes. Se documentaron tres casos de celulitis posoperatoria tras la extirpación de una hemorroide externa trombosada, una hemorroidopexia y una hemorroidectomía de Whitehead. No se administraron antibióticos intravenosos postoperatorios. No se documentaron casos de sepsis pélvica. LIMITACIONES: El carácter retrospectivo del estudio y la heterogeneidad de la población estudiada. CONCLUSIONES: Estos datos sugieren que los procedimientos ambulatorios y quirúrgicos son seguros y viables en pacientes con inmunosupresión. (AI-generated translation )

Abstract Artificial intelligence (AI) holds significant potential to enhance various aspects of oncology, spanning the cancer care continuum. This review provides an overview of current and emerging AI applications, from risk assessment and early detection to treatment and supportive care. AI‐driven tools are being developed to integrate diverse data sources, including multi‐omics and electronic health records, to improve cancer risk stratification and personalize prevention strategies. In screening and diagnosis, AI algorithms show promise in augmenting the accuracy and efficiency of medical image analysis and histopathology interpretation. AI also offers opportunities to refine treatment planning, optimize radiation therapy, and personalize systemic therapy selection. Furthermore, AI is explored for its potential to improve survivorship care by tailoring interventions and to enhance end‐of‐life care through improved symptom management and prognostic modeling. Beyond care delivery, AI augments clinical workflows, streamlines the dissemination of up‐to‐date evidence, and captures critical patient‐reported outcomes for clinical decision support and outcomes assessment. However, the successful integration of AI into clinical practice requires addressing key challenges, including rigorous validation of algorithms, ensuring data privacy and security, and mitigating potential biases. Effective implementation necessitates interdisciplinary collaboration and comprehensive education for health care professionals. The synergistic interaction between AI and clinical expertise is crucial for realizing the potential of AI to contribute to personalized and effective cancer care. This review highlights the current state of AI in oncology and underscores the importance of responsible development and implementation.

Abstract Intracranial hemorrhage (ICH) and resulting neurologic disability are severe complications for a subset of infants with severe hemophilia A (HA). Although prophylactic factor replacement reduces bleeding risk, it is typically delayed until after age 1 year due to risks associated with central venous access placement. Emicizumab, a subcutaneous activated factor VIII (FVIII) mimetic, has demonstrated safety and efficacy in preventing ICH in infants aged <12 months in the HAVEN 7 trial. Despite its high cost, the cost-effectiveness of emicizumab prophylaxis initiated during the first year of life for infants with severe HA is not known. We developed a Markov cohort model to compare emicizumab prophylaxis to standard care (no prophylaxis) in infants aged 0 to 1 year with severe HA without FVIII inhibitors. The analysis was conducted from a US societal perspective over a lifetime horizon across all accepted willingness-to-pay (WTP) thresholds. The primary outcome was the incremental cost-effectiveness ratio (ICER) in US dollar per quality-adjusted life-year (QALY). Emicizumab prophylaxis and standard care accrued 25.6 and 25.1 QALYs at costs of $13.12 million and $13.07 million, respectively, resulting in an ICER of $99 900 per QALY (95% credible interval [CI], 84 000-120 000). Scenario analysis examining prophylaxis with low-dose emicizumab resulted in an ICER of $19 600 per QALY (95% CI, 12 000-29 000). Probabilistic sensitivity analyses showed that standard-dose emicizumab is the cost-effective strategy in 100%, 66%, and 0% of 10 000 Monte Carlo iterations at WTP thresholds of $150 000, $104 000, and $50 000 per QALY, respectively, and in 100% across all WTP thresholds for low-dose emicizumab.

Gastrointestinal (GI) defects pose a significant clinical challenge, impacting patient outcomes and healthcare costs. Endoscopic closure techniques have emerged as effective and minimally invasive approaches to manage these defects. This review explores the various endoscopic techniques, including over-the-scope clips (OTSC), endo suturing systems, through-the-scope (TTS) clips, and the X-Tack system. Each technique offers distinct advantages and limitations, making it suitable for specific clinical scenarios. While these devices have demonstrated promising results in clinical practice, further research is needed to optimize their use and address knowledge gaps. Large-scale randomized controlled trials are essential to establish evidence-based guidelines for device selection and procedural techniques. By embracing technological advancements and addressing research limitations, the field of endoscopic closure devices has the potential to revolutionize GI care, leading to improved patient outcomes and expanded therapeutic possibilities.

BACKGROUND/OBJECTIVE Patient- and family-centered rounds (PFCR) have become a pediatric standard of care. However, rounds experiences of families using languages other than English (LOE)—particularly languages other than English or Spanish (LOES; eg, Arabic)—receive less focus. We aimed to identify differences in PFCR communication and engagement by language. METHODS We analyzed postintervention data from a 21-center structured PFCR study, assessing communication practices, quality, and family and nurse engagement during PFCR. Logistic regression adjusted by site compared PFCR between families using (1) LOE vs English, (2) Spanish vs English, and (3) LOES vs English. RESULTS Among 3051 PFCR encounters, 348 (11.4%) involved LOE (Spanish = 260; LOES = 85). Interpretation was not used in 7.2%, 5.8%, and 9.4% of encounters using LOE, Spanish, and LOES, respectively. PFCR in the following groups had lower adjusted odds (adjusted odds ratio [95% CI]) for the following domains: (1) LOE vs English: including providing verbal patient summaries (0.66 [0.46–0.95]), explaining diagnoses and differentials (0.62 [0.44–0.88]), family engagement (0.34 [0.20–0.57]), nursing inclusion (0.75 [0.60–0.93]), and nursing engagement (0.69 [0.52–0.90]). (2) Spanish vs English: diagnoses/differentials being explained (0.56 [0.37–0.85]), family engagement (0.35 [0.18–0.67]), nursing inclusion (0.77 [0.59–1.00]), and nursing engagement (0.68 [0.52–0.89]). (3) LOES vs English: families sharing concerns (0.66 [0.47–0.93]), family engagement (0.30 [0.16–0.54]), and nursing inclusion (0.74 [0.55–0.99]). CONCLUSION Even after implementing a PFCR intervention, families using LOE—especially LOES—experienced significant disparities in communication and engagement. Future approaches to improving PFCR should emphasize language access and promote nurse and family engagement for families using LOE, particularly LOES.