Project description:Chromosomal translocations harbored by cancer genomes are important oncogenic drivers. In MLL rearranged acute leukemia (MLLre) MLL/KMT2A fuses with over 90 partner genes. Mechanistic studies provided clues of MLL fusion protein leukemogenic potential, but models failed to fully recapitulate the disease. Recently, expression of oncogenic fusion circular RNAs (f-circ) by MLL-AF9 fusion was proven. This discovery, together with emerging data on the importance and diversity of circRNAs formed the incentive to study the circRNAs of the MLL recombinome. Through interactions with other RNAs, such as microRNAs, and with proteins, circRNAs regulate cellular processes also related to cancer development. CircRNAs can translate into functional peptides too. MLL and most of the 90 MLL translocation partners do express circRNAs and exploration of our RNA-seq dataset of sorted blood cell populations provided new data on alternative circular isoform generation and expression variability of circRNAs of the MLL recombinome. Further, we provided evidence that rearrangements of MLL and three of the main translocation partner genes can impact circRNA expression, supported also by preliminary observations in leukemic cells. The emerging picture underpins the view that circRNAs are worthwhile to be considered when studying MLLre leukemias and provides a new perspective on the impact of chromosomal translocations in cancer cells at large.
Project description:ObjectivesDuring the COVID-19 pandemic, face-to-face rheumatology follow-up appointments were mostly replaced with telephone or virtual consultations in order to protect vulnerable patients. We aimed to investigate the perspectives of rheumatology patients on the use of telephone consultations compared with the traditional face-to-face consultation.MethodsWe carried out a retrospective survey of all rheumatology follow-up patients at the Royal Wolverhampton Trust who had received a telephone consultation from a rheumatology consultant during a 4-week period via an online survey tool.ResultsSurveys were distributed to 1213 patients, of whom 336 (27.7%) responded, and 306 (91.1%) patients completed all components of the survey. Overall, an equal number of patients would prefer telephone clinics or face-to-face consultations for their next routine appointment. When divided by age group, the majority who preferred the telephone clinics were <50 years old [χ2 (d.f. = 3) = 10.075, P = 0.018]. Prevalence of a smartphone was higher among younger patients (<50 years old: 46 of 47, 97.9%) than among older patients (≥50 years old: 209 of 259, 80.7%) [χ2 (d.f. = 3) = 20.919, P < 0.001]. More patients reported that they would prefer a telephone call for urgent advice (168, 54.9%).ConclusionMost patients interviewed were happy with their routine face-to-face appointment being switched to a telephone consultation. Of those interviewed, patients >50 years old were less likely than their younger counterparts to want telephone consultations in place of face-to-face appointments. Most patients in our study would prefer a telephone consultation for urgent advice. We must ensure that older patients and those in vulnerable groups who value in-person contact are not excluded. Telephone clinics in some form are here to stay in rheumatology for the foreseeable future.
Project description:IntroductionAdvancing age is the most important risk factor for cancer. Collaborations with medical and surgical-oncology divisions, and supportive services are required to assist older adults with cancer through their assessment and treatment trajectories. This often requires numerous clinical encounters which can increase treatment burden on the patient and caregivers. One solution that may lighten this load is the use of telemedicine.MethodsAt Memorial Sloan Kettering, the Cancer and Aging Interdisciplinary Team (CAIT) clinic risk stratifies and optimizes older adults planned for medical cancer treatment. We analyzed patients seen in the CAIT clinic between May 2021 and December 2023, focusing on their utilization of telemedicine, and on the differences in characteristics of the visits and the results of the Geriatric Assessment based on visit type.ResultsOf the 288 patients (age range 67-100) evaluated, the majority (77%) chose telemedicine visits. Older age, lower educational status, living in New York City, abnormal cognitive screen, impaired performance measures, IADL dependency and having poor social support were all associated with choosing an in-person visit as opposed to telemedicine.ConclusionOlder patients with cancer frequently choose and can complete telemedicine visits. Efforts should be directed to develop an infrastructure for remote engagement, improving reach into rural and underserved areas, decreasing the burden generated by multiple appointments.
Project description:Immune escape and impaired immune surveillance have been identified as emerging hallmarks of cancer.1 Multiple myeloma represents a genuine example of disrupted immune surveillance characterized by: impaired antibody production, deregulation of the T and natural killer cell compartment, disruption of antigen presentation machinery, upregulation of inhibitory surface ligands, and recruitment of immunosuppressive cells. Although the potential value of immunotherapeutic interventions had a clear antecedent in the graft-versus-myeloma effect induced by allogeneic stem cell transplant and donor lymphocyte infusions, it is only recently that this field has faced a real revolution. In this review we discuss the current results obtained with immune approaches in patients with multiple myeloma that have placed this disease under the scope of immuno-oncology, bringing new therapeutic opportunities for the treatment of multiple myeloma patients.
Project description:Chromosomal translocations harbored by cancer genomes are important oncogenic drivers. In MLL rearranged acute leukemia (MLLre) MLL/KMT2A fuses with over 90 partner genes. Mechanistic studies provided clues of MLL fusion protein leukemogenic potential, but models failed to fully recapitulate the disease. Recently, expression of oncogenic fusion circular RNAs (f-circ) by MLL-AF9 fusion was proven. This discovery, together with emerging data on the importance and diversity of circRNAs formed the incentive to study the circRNAs of the MLL recombinome. Through interactions with other RNAs, such as microRNAs, and with proteins, circRNAs regulate cellular processes also related to cancer development. CircRNAs can translate into functional peptides too. MLL and most of the 90 MLL translocation partners do express circRNAs and exploration of our RNA-seq dataset of sorted blood cell populations provided new data on alternative circular isoform generation and expression variability of circRNAs of the MLL recombinome. Further, we provided evidence that rearrangements of MLL and three of the main translocation partner genes can impact circRNA expression, supported also by preliminary observations in leukemic cells. The emerging picture underpins the view that circRNAs are worthwhile to be considered when studying MLLre leukemias and provides a new perspective on the impact of chromosomal translocations in cancer cells at large.
Project description:IntroductionSafety concerns surrounding the coronavirus 2019 pandemic led to the prohibition of student rotations outside their home institutions. This resulted in emergency medicine (EM)-bound students having less specialty experience and exposure to outside programs and practice environments, and fewer opportunities to gain additional Standardized Letters of Evaluation, a cornerstone of the EM residency application. We filled this void by implementing a virtual clerkship.MethodsWe created a two-week virtual, fourth-year visiting clerkship focused on advanced medical knowledge topics, social determinants of health, professional development, and professional identity formation. Students completed asynchronous assignments and participated in small group-facilitated didactic sessions. We evaluated the virtual clerkship with pre- and post-medical knowledge tests and evaluative surveys.ResultsWe hosted 26 senior medical students over two administrations of the same two-week virtual clerkship. Students had a statistically significant improvement on the medical knowledge post-tests compared to pre-tests (71.7% [21.5/30] to 76.3% [22.9/30]). Students reported being exposed to social determinants of health concepts they had not previously been exposed to. Students appreciated the interactive nature of the sessions; networking with other students, residents, and faculty; introduction to novel content regarding social determinants of health; and exposure to future career opportunities. Screen time, technological issues, and mismatch between volume of content and time allotted were identified as potential challenges and areas for improvement.ConclusionWe demonstrate that a virtual EM visiting clerkship is feasible to implement, supports knowledge acquisition, and is perceived as valuable by participants. The benefits seen and challenges faced in the development and implementation of our clerkship can serve to inform future virtual clerkships, which we feel is a complement to traditional visiting clerkships even though in-person clerkships have been re-established.