Conclusive demonstration of iatrogenic Alzheimer's disease transmission in a model of stem cell transplantation.

The risk of iatrogenic disease is often underestimated as a concern in contemporary medical procedures, encompassing tissue and organ transplantation, stem cell therapies, blood transfusions, and the administration of blood-derived products. In this context, despite the prevailing belief that Alzheimer's disease (AD) manifests primarily in familial and sporadic forms, our investigation reveals an unexpected transplantable variant of AD in a preclinical context, potentially indicating iatrogenic transmission in AD patients. Through adoptive transplantation of donor bone marrow stem cells carrying a mutant human amyloid precursor protein (APP) transgene into either APP-deficient knockout or normal recipient animals, we observed rapid development of AD pathological hallmarks. These pathological features were significantly accelerated and emerged within 6-9 months post transplantation and included compromised blood-brain barrier integrity, heightened cerebral vascular neoangiogenesis, elevated brain-associated ß-amyloid levels, and cognitive impairment. Furthermore, our findings underscore the contribution of ß-amyloid burden originating outside of the central nervous system to AD pathogenesis within the brain. We conclude that stem cell transplantation from donors harboring a pathogenic mutant allele can effectively transfer central nervous system diseases to healthy recipients, mirroring the pathogenesis observed in the donor. Consequently, our observations advocate for genomic sequencing of donor specimens prior to tissue, organ, or stem cell transplantation therapies, as well as blood transfusions and blood-derived product administration, to mitigate the risk of iatrogenic diseases.

The clinical impact of COVID-19 on patients with cancer in British Columbia: An observational study.

Objective: We evaluated survival outcomes for patients with cancer and COVID-19 in this population-based study. Methods: A total of 631 patients who tested positive for severe acute respiratory syndrome coronavirus 2 and were seen at BC Cancer between 03/03/2020 and 01/21/2021 were included, of whom 506 had a diagnosis of cancer and PCR-confirmed positive test for coronavirus disease 2019. Patient clinical characteristics were retrospectively reviewed and the influence of demographic data, cancer diagnosis, comorbidities, and anticancer treatment(s) on survival following severe acute respiratory syndrome coronavirus 2 infection were analyzed. Results: Age ≥65 years (Hazard Ratio [HR] 4.77, 95% Confidence Interval [CI] 2.72-8.35, P < 0.0001), those with Eastern Cooperative Oncology Group Performance Status ≥2 (HR 8.36, 95% CI 2.89-24.16, P < 0.0001), hypertension (HR 3.17, 95% CI 1.77-5.66, P < 0.0001), and metastatic/advanced stage (HR 3.70, 95% CI 1.77-7.73, P < 0.0001) were associated with worse coronavirus disease 2019 specific survival outcomes following severe acute respiratory syndrome coronavirus 2 infection. Patients with lung cancer had the highest 30-day COVID-19 specific mortality (25.0%), followed by genitourinary (18.1%), gastrointestinal (16.0%), and other cancer types (<10.0%). Patients with the highest 30-day coronavirus disease 2019 specific mortality according to treatment type were those on chemotherapy (23.0%), rituximab (22.2%), and immunotherapy (16.7%) while patients on hormonal treatments (2.2%) had better survival outcomes (P = 0.041) compared to those on other anticancer treatments. Conclusion: This study provides further evidence that patients with cancer are at increased risk of mortality from coronavirus disease 2019 and emphasizes the need for vaccination.

Well-Differentiated Grade 3 Neuroendocrine Tumors: Characteristics, Treatments, and Outcomes From a Population-Based Study.

OBJECTIVES: We evaluated a population-based cohort of metastatic well-differentiated grade 3 gastroenteropancreatic neuroendocrine tumors (G3 NETs) to describe their characteristics, prognosis, and treatment outcomes. METHODS: The British Columbia provincial database was queried for G3 NETs diagnosed 2004 to 2021, and charts were reviewed to describe clinical features and outcomes. RESULTS: Forty-one patients were identified, most were diagnosed with pancreatic (58.5%) or midgut (26.8%) primary tumor and Ki-67 was less than 55% in 68.3%. The primary was resected in 19 (46.3%) with median disease-free survival of 25.2 months. Once metastatic, patients received a median of one line of systemic therapy. Median overall survival with metastatic disease was 33.8 months. Median progression-free survival was longest in patients treated with capecitabine-temozolomide (20.6 months) or somatostatin analogs (7.9 months), while etoposide-platinum provided little benefit (2.4 months). Limited data of efficacy for targeted therapies and radionuclide therapy was available. Seven patients (17.1%) were also treated with local therapies, which were associated with improved overall survival (median not reached, hazard ratio, 0.23; P = 0.012). CONCLUSIONS: Capecitabine-temozolomide and somatostatin analogs were associated with clinically meaningful benefit, and use of local therapies provided benefits in selected patients. Multidisciplinary discussion is essential to optimize individual outcomes in this heterogeneous population.