RESUMO
Chimeric antigen receptor (CAR) modified T-cell therapy, a unique platform technology highlighting precision medicine through utilization of molecular biology and cell-based therapeutics has shown unprecedented rates in patients with hematological malignancies such as acute lymphocyte leukemia, non-Hodgkin's lymphoma and multiple myeloma (MM). With the approval of CD19-targeted CAR T-cells by the Food and Drug Administration in acute lymphoblastic leukemia (ALL) and NHL, this technology is positioned for aggressive expansion to combination therapeutic opportunities and proof of principle towards utility in other malignant disorders. However, despite the impressive results seen with hematological malignancies, CAR T-cells have shown limited efficacy in solid tumors with several unsuccessful preclinical studies. Regardless, these attempts have provided us with a better understanding of the imminent challenges specific to solid tumors even if they have not so far led to expanded clinical treatment opportunities outside ALL/NHL/MM. This review summarizes our current understanding of CAR T-cell mechanism of action, while presenting the major limitations of CAR T-cell derived treatments in solid tumors. We further discuss recent findings and present new potential strategies to overcome the challenges facing solid tumor targeting by CAR T-cell platforms.
Assuntos
Imunoterapia Adotiva , Linfoma não Hodgkin/terapia , Mieloma Múltiplo/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Receptores de Antígenos Quiméricos/imunologia , Antígenos CD19/imunologia , Humanos , Estudo de Prova de ConceitoRESUMO
Natural killer (NK) cells lead immune surveillance against cancer and early elimination of small tumors. Owing to their ability to engage tumor targets without the need of specific antigen, the therapeutic potential of NK cells has been extensively explored in hematological malignancies. In solid tumors, however, their role in the clinical arena remains poorly exploited despite a broad accumulation of preclinical data. In this article, we review our current knowledge of NK cells' biology, and highlight the challenges facing NK cell antitumor strategies in solid tumors. We further summarize the abundant preclinical attempts at overcoming these challenges, present past and ongoing clinical trial data and finally discuss the potential impact of novel insights on the development of NK cell-based therapies.
Assuntos
Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Animais , Humanos , Vigilância Imunológica , Imunoterapia Adotiva , Neoplasias/etiologia , Neoplasias/metabolismo , Neoplasias/terapia , Células-Tronco Neoplásicas/metabolismo , Receptores KIR/metabolismo , Transdução de Sinais , Evasão Tumoral/genética , Evasão Tumoral/imunologiaRESUMO
PURPOSE OF STUDY: Hospital overcrowding and delays in discharge are serious issues in the modern health care landscape and can lead to poor patient outcomes and health care personnel (HCP) burnout. The goal of this project was to develop a collaborative forum where HCP representing the entire spectrum of the inpatient care team, including case management team members, could connect to discuss challenges and barriers to patient discharge. The following describes the development, implementation, and outcomes of the discharge SWAT (Solutions, Wins, Actions, and Tactics) team, which is a 30-min virtual daily meeting where discussion is primarily centered around challenges in discharging individual patients and addressing case manager needs. The primary aim of SWAT meetings is fostering a positive atmosphere to address barriers to discharge while prioritizing patient care and outcomes. PRIMARY PRACTICE SETTING: This study was conducted in a 40-hospital academic health system in the United States. METHODOLOGY AND SAMPLE: SWAT meetings were first implemented at a representative flagship facility in a health system. HCP at this first facility were surveyed to assess satisfaction with SWAT meetings. SWAT meetings then were implemented at the majority of facilities in a 40-hospital academic health system. During SWAT implementation, average inpatient length of stay (LOS) and patient care transitions were monitored for participating and nonparticipating service lines. RESULTS: Among surveyed HCP, the majority view SWAT meetings favorably and reported that it was a valuable use of their time and positively impacted their work in the patient discharge space. Nonprovider and case management staff in particular valued the SWAT meetings and found them beneficial. LOS remained stable for patients under the care of participating providers, despite the upheaval of the ongoing COVID-19 pandemic, and the research team also observed a positive impact of SWAT meetings on appropriate inpatient care transitions.
Assuntos
COVID-19 , Moral , Pandemias , Alta do Paciente , Humanos , COVID-19/epidemiologia , Alta do Paciente/normas , SARS-CoV-2 , Masculino , Feminino , Estados Unidos , Equipe de Assistência ao Paciente/organização & administração , Adulto , Pessoa de Meia-Idade , Administração de Caso/organização & administração , Comunicação , Pessoal de Saúde/psicologiaRESUMO
Accessory spleen (AS) is a benign condition, where ectopic spleen tissue can be found elsewhere in the abdomen and pelvis, with approximately 20% of cases located at or in the tail of the pancreas. When discovered on imaging, it can be mistaken for conditions that do require surgical removal, including neuroendocrine tumor, and so accurate diagnosis of AS can prevent unnecessary surgery. Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is a commonly performed diagnostic modality that can lead to a confirmatory diagnosis of AS. We present a case of AS diagnosed at our institution by EUS-FNA and review the literature for all reported cases of AS that have been confirmed by EUS-FNA.
Assuntos
Coristoma/patologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Pancreatopatias/patologia , Neoplasias Pancreáticas/patologia , Baço , Algoritmos , Diagnóstico Diferencial , Feminino , Humanos , Adulto JovemRESUMO
BACKGROUND: Internists commonly perform invasive procedures, but serious deficiencies exist in procedure training during residency. OBJECTIVE: Evaluate a comprehensive, inpatient procedure service rotation (MPS) to improve Internal Medicine residents' comfort and self-perceived knowledge in performing lumbar puncture, abdominal paracentesis, thoracentesis, arthrocentesis, and central venous catheterization (CVC). DESIGN: The MPS comprised 1 faculty physician and 1-3 residents rotating for 2 weeks. It incorporated lectures, a textbook, instructional videos, supervised practice on mannequins, and inpatient procedures directly supervised by the faculty physician. We measured MPS impact using pre- and post-MPS rotation surveys, and surveyed all residents at academic year-end. MEASUREMENTS AND MAIN RESULTS: Thirty-nine categorical Internal Medicine residents completed the required rotation and surveys over the 2004-2005 academic year, performing 325 procedures. Post-MPS, the percentage of residents reporting comfort performing procedures rose 15-36% (p < .05 except for arthrocentesis, and CVC via internal jugular and femoral veins). The fraction desiring more training fell 26-51% (all p < .05). After the MPS rotation, self-rated knowledge increased in all surveyed aspects of the procedures. The year-end survey showed that improvements persisted. Comfort at year-end, for all procedures except abdominal paracentesis, was significantly higher among residents who rotated through the MPS than among those who had not. Self-reported compliance with recommended antiseptic measures was 75% for residents who completed the MPS, and 28% for those who had not (p < 0.001). CONCLUSIONS: A comprehensive procedure service rotation of 2 weeks duration substantially improved residents' comfort and self-perceived knowledge in performing invasive procedures. These benefits persisted at least to the end of the academic year.