The application, safety, and future of ex vivo immune cell therapies and prognosis in different malignancies.

Introduction: Immunotherapy has revolutionized how cancer is treated. Many of these immunotherapies rely on ex vivo expansion of immune cells, classically T cells. Still, several immunological obstacles remain, including tumor impermeability by immune cells and the immunosuppressive nature of the tumor microenvironment (TME). Logistically, high costs of treatment and variable clinical responses have also plagued traditional T cell-based immunotherapies. Methods: To review the existing literature on cellular immunotherapy, the PubMed database was searched for publications using variations of the phrases "cancer immunotherapy", "ex vivo expansion", and "adoptive cell therapy". The Clinicaltrials.gov database was searched for clinical trials related to ex vivo cellular therapies using the same phrases. The National Comprehensive Cancer Network guidelines for cancer treatment were also referenced. Results: To circumvent the challenges of traditional T cell-based immunotherapies, researchers have developed newer therapies including tumor infiltrating lymphocyte (TIL), chimeric antigen receptor (CAR), T cell receptor (TCR) modified T cell, and antibody-armed T cell therapies. Additionally, newer immunotherapeutic strategies have used other immune cells, including natural killer (NK) and dendritic cells (DC), to modulate the T cell immune response to cancers. From a prognostic perspective, circulating tumor cells (CTC) have been used to predict cancer morbidity and mortality. Conclusion: This review highlights the mechanism and clinical utility of various types of ex vivo cellular therapies in the treatment of cancer. Comparing these therapies or using them in combination may lead to more individualized and less toxic chemotherapeutics.

Innovations and Implementation of Telemedicine in Surgical Clinics Beyond COVID-19: A Narrative Review.

Introduction: Telemedicine has emerged as a powerful tool in the delivery of health care to surgical patients and innovations are developing to address challenges in the technology, enhancing consumer-provider encounters while located remotely. Our study aims at collating and commenting on the published evidence for how current challenges in telemedicine for surgical clinics are met by innovations currently in development. We also comment on the implementation and monitoring strategies for telemedicine. Methods: Databases searched included: PubMed, OVID Medline, Embase, Scopus, Web of Science, and review of reference lists. Key words used were "telemedicine"; "telehealth"; "videoconference"; "outpatient"; and "surgical clinic." For inclusion, articles required to be in English, published between 2000 and 2021, were in an outpatient surgical setting, and if they had a focus during the COVID-19 pandemic. Results: Three hundred forty-five articles were identified and screened, so that 73 articles were included in the review. Almost all articles were from Western countries (n = 69), mostly in surgical journals (n = 39) and from a range of sub-specialties, but pre-dominantly orthopedics (n = 12) and general surgery (n = 9). The majority were original comparative studies, with 31 studies directly comparing telemedicine with in-person appointments and 22 articles focused on implementation during COVID-19. Discussion/Conclusion: Advanced telecommunication technology has enabled telemedicine to become an effective and safe form of health care delivery, with high consumer and provider satisfaction. Innovative protocol and technology developments have addressed the limitations of telemedicine. Sophisticated and familiar medical software integrates with electronic medical records to automate and streamline documentation, consent, and billing processes. Surgical clinics are investing in telehealth workflow co-ordination and information technology support to troubleshoot any technical difficulties as well as education for providers and consumers to address technology illiteracy. As health care services continue to transition their systems to an online network, further research is required to understand the ability and assess the feasibility of telemedicine to fully integrate.

Current and future use of telemedicine in surgical clinics during and beyond COVID-19: A narrative review.

INTRODUCTION: Telemedicine has emerged as a powerful tool in the delivery of healthcare to surgical patients and enhances clinician-patient encounters during all phases of patient care. Our study aims were: to review the current use and applicability of telemedicine; evaluate its suitability, safety and effectiveness in a surgical outpatient setting, particularly in the era of social distancing restrictions and provide insight into future applications. METHODS: Databases searched included: PubMed, OVID Medline, Embase, Scopus, Web of Science and review of reference lists. Key words used were "telemedicine"; "telehealth"; "videoconference"; "outpatient" and "surgical clinic". For inclusion, articles required to be in English, published between 2000 and 2021, were in an outpatient surgical setting and if they had a focus during the COVID-19 pandemic. RESULTS: 335 articles were identified and screened, so that 63 articles were included in the review. Almost all articles were from Western countries (n = 60), mostly in surgical journals (n = 35) and from a range of sub-specialities, but pre-dominantly orthopaedics (n = 12) and general surgery (n = 7). The majority were original comparative studies where 31 studies directly compared telemedicine to in-person appointments and 14 papers focused on implementation during COVID-19. DISCUSSION/CONCLUSIONS: Telemedicine has been safely used across various phases of surgical outpatient care, with its effectiveness evaluated by clinical outcomes, economics and user/provider satisfaction. Telemedicine has multiple accepted benefits including time efficiency, patient/healthcare cost savings and community access, but with reported limitations of clinical uncertainty, technology infrastructure requirements, cybersecurity vulnerabilities and healthcare regulatory restraints. These limitations are being overcome by accelerated implementation during COVID-19 via fast-tracked practice development. Further work is required via development of research protocols to refine the application of emerging telemedicine technologies and their applicability to different surgical sub-specialties.

TP63 isoform expression is linked with distinct clinical outcomes in cancer.

BACKGROUND: Half of muscle-invasive bladder cancer patients will relapse with metastatic disease and molecular tests to predict relapse are needed. TP63 has been proposed as a prognostic biomarker in bladder cancer, but reports associating it with clinical outcomes are conflicting. Since TP63 is expressed as multiple isoforms, we hypothesized that these conflicting associations with clinical outcome may be explained by distinct opposing effects of differential TP63 isoform expression. METHODS: Using RNA-Seq data from The Cancer Genome Atlas (TCGA), TP63 isoform-level expression was quantified and associated with clinical covariates (e.g. survival, stage) across 8,519 patients from 29 diseases. A comprehensive catalog of TP63 isoforms was assembled using gene annotation databases and de novo discovery in bladder cancer patients. Quantifications and un-annotated TP63 isoforms were validated using quantitative RT-PCR and a separate bladder cancer cohort. FINDINGS: DNp63 isoform expression was associated with improved bladder cancer patient survival in patients with a luminal subtype (HR = 0.89, CI 0.80-0.99, Cox p = 0.034). Conversely, TAp63 isoform expression was associated with reduced bladder cancer patient survival in patients with a basal subtype (HR = 2.35, CI 1.64-3.37, Cox p < 0.0001). These associations were observed in multiple TCGA disease cohorts and correlated with epidermal differentiation (DNp63) and immune-related (TAp63) gene signatures. INTERPRETATION: These results comprehensively define TP63 isoform expression in human cancer and suggest that TP63 isoforms are involved in distinct transcriptional programs with opposing effects on clinical outcome.