The CD3-Zeta Chimeric Antigen Receptor Overcomes TCR Hypo-Responsiveness of Human Terminal Late-Stage T Cells

Adoptive therapy of malignant diseases with tumor-specific cytotoxic T cells showed remarkable efficacy in recent trials. Repetitive T cell receptor (TCR) engagement of target antigen, however, inevitably ends up in hypo-responsive cells with terminally differentiated KLRG-1+ CD57+ CD7− phenotype limiting their therapeutic efficacy. We here revealed that hypo-responsiveness of CMV-specific late-stage CD8+ T cells is due to reduced TCR synapse formation compared to younger cells. Membrane anchoring of TCR components contributes to T cell hypo-responsiveness since dislocation of galectin-3 from the synapse by swainsonine restored both TCR synapse formation and T cell response. Transgenic expression of a CD3-zeta signaling chimeric antigen receptor (CAR) recovered hypo-responsive T cells to full effector functions indicating that the defect is restricted to TCR membrane components while synapse formation of the transgenic CAR was not blocked. CAR engineered late-stage T cells released cytokines and mediated redirected cytotoxicity as efficiently as younger effector T cells. Our data provide a rationale for TCR independent, CAR mediated activation in the adoptive cell therapy to avoid hypo-responsiveness of late-stage T cells upon repetitive antigen encounter

The Transcriptome of the Nosocomial Pathogen Enterococcus faecalis V583 Reveals Adaptive Responses to Growth in Blood

gains access to the bloodstream and establishes a persistent infection is not well understood.. infections

Malignant Transformation of Endometriosis in the Ischioanal Fossa

We present the case of a 28-year-old nulliparous female with malignant transformation of an ectopic focus of endometriosis in the right ischioanal fossa. A 28-year-old nulliparous patient with a past medical history of polycystic ovarian syndrome (PCOS) was diagnosed with endometrioid adenocarcinoma in her right ischioanal fossa. Initially, patient presented to an emergency department and underwent a CT scan of the appendix to rule out appendicitis. A multiloculated cystic lesion adjacent to the right obturator internus muscle was found. She underwent surgical resection of the mass, which confirmed FIGO grade 2 endometrioid adenocarcinoma, followed by localized radiation therapy. Malignancy arising in endometriosis is rare, and the influence of PCOS on the rate of malignant transformation is not well established

Robotic surgery during the COVID pandemic: why now and why for the future.

Health care has changed in unprecedented ways since the first reported cases of COVID-19. With global case rates continuing to rise and government restrictions beginning to loosen, many worry that a second wave in our future. In many hospitals around the world, non-emergent surgeries were put on hold as hospitals were transformed into COVID centers. As surgeons and administrators do their best to reinstate non-emergent procedures, guidance is sought from any and all reliable sources. Robotic surgery has many known and demonstrated benefits over open surgery and often over conventional laparoscopy. In this commentary, we aim to highlight some of the advantages robotic surgery may offer during this uniquely challenging time in health care

Robotic surgery during the COVID pandemic: why now and why for the future.

Health care has changed in unprecedented ways since the first reported cases of COVID-19. With global case rates continuing to rise and government restrictions beginning to loosen, many worry that a second wave in our future. In many hospitals around the world, non-emergent surgeries were put on hold as hospitals were transformed into COVID centers. As surgeons and administrators do their best to reinstate non-emergent procedures, guidance is sought from any and all reliable sources. Robotic surgery has many known and demonstrated benefits over open surgery and often over conventional laparoscopy. In this commentary, we aim to highlight some of the advantages robotic surgery may offer during this uniquely challenging time in health care

A narrative review of platelet-rich plasma (PRP) in reproductive medicine.

PURPOSE: Platelet-rich plasma (PRP) has become a novel treatment in various aspects of medicine including orthopedics, cardiothoracic surgery, plastic surgery, dermatology, dentistry, and diabetic wound healing. PRP is now starting to become an area of interest in reproductive medicine more specifically focusing on infertility. Poor ovarian reserve, menopause, premature ovarian failure, and thin endometrium have been the main areas of research. The aim of this article is to review the existing literature on the effects of autologous PRP in reproductive medicine providing a summation of the current studies and assessing the need for additional research. METHODS: A literature search is performed using PubMed, MEDLINE, and CINAHL Plus to identify studies focusing on the use of PRP therapy in reproductive medicine. Articles were divided into 3 categories: PRP in thin lining, PRP in poor ovarian reserve, and PRP in recurrent implantation failure. RESULTS: In women with thin endometrium, the literature shows an increase in endometrial thickness and increase in chemical and clinical pregnancy rates following autologous PRP therapy. In women with poor ovarian reserve, autologous intraovarian PRP therapy increased anti-Mullerian hormone (AMH) levels and decreased follicle-stimulating hormone (FSH), with a trend toward increasing clinical and live birth rates. This trend was also noted in women with recurrent implantation failure. CONCLUSIONS: Limited literature shows promise in increasing endometrial thickness, increasing AMH, and decreasing FSH levels, as well as increasing chemical and clinical pregnancy rates. The lack of standardization of PRP preparation along with the lack of large randomized controlled trials needs to be addressed in future studies. Until definitive large RCTs are available, PRP use should be considered experimental

Augmented Realities, Artificial Intelligence, and Machine Learning: Clinical Implications and How Technology Is Shaping the Future of Medicine.

Technology has been integrated into every facet of human life, and whether it is completely advantageous remains unknown, but one thing is for sure; we are dependent on technology. Medical advances from the integration of artificial intelligence, machine learning, and augmented realities are widespread and have helped countless patients. Much of the advanced technology utilized by medical providers today has been borrowed and extrapolated from other industries. There remains no great collaboration between providers and engineers, which may be why medicine is only in its infancy of innovation with regards to advanced technologic integration. The purpose of this narrative review is to highlight the different technologies currently being utilized in a variety of medical specialties. Furthermore, we hope that by bringing attention to one shortcoming of the medical community, we may inspire future innovators to seek collaboration outside of the purely medical community for the betterment of all patients seeking care