Intracerebroventricular B7-H3-targeting CAR T cells for diffuse intrinsic pontine glioma: a phase 1 trial.

Diffuse intrinsic pontine glioma (DIPG) is a fatal central nervous system (CNS) tumor that confers a median survival of 11 months. As B7-H3 is expressed on pediatric CNS tumors, we conducted BrainChild-03, a single-center, dose-escalation phase 1 clinical trial of repetitive intracerebroventricular (ICV) dosing of B7-H3-targeting chimeric antigen receptor T cells (B7-H3 CAR T cells) for children with recurrent or refractory CNS tumors and DIPG. Here we report results from Arm C, restricted to patients with DIPG.

Patient With an Anomalous Left Coronary Artery and Hypertrophic Obstructive Cardiomyopathy.

A 39-year-old man presented with angina and a high-sensitivity troponin-T of 61 ng/L. Initial workup revealed the presence of left ventricular hypertrophy, an anomalous left main coronary artery, and no coronary atherosclerosis. This case demonstrates how multimodality imaging was used to elucidate the primary cause of the patient's angina.

Locoregional CAR T Cells for the Treatment of CNS Tumors in Children: Investigational Drug Service Pharmacy Activities.

Background: A major obstacle in translating the therapeutic potential of chimeric antigen receptor (CAR) T cells to children with central nervous system (CNS) tumors is the blood-brain barrier. To overcome this limitation, preclinical and clinical studies have supported the use of repeated, locoregional intracranial CAR T-cell delivery. However, there is limited literature available describing the process for the involvement of an investigational drug service (IDS) pharmacy, particularly in the setting of a children's hospital with outpatient dosing for CNS tumors.

Drug-regulated CD33-targeted CAR T cells control AML using clinically optimized rapamycin dosing.

Chimeric antigen receptor (CAR) designs that incorporate pharmacologic control are desirable; however, designs suitable for clinical translation are needed. We designed a fully human, rapamycin-regulated drug product for targeting CD33+ tumors called dimerizaing agent-regulated immunoreceptor complex (DARIC33). T cell products demonstrated target-specific and rapamycin-dependent cytokine release, transcriptional responses, cytotoxicity, and in vivo antileukemic activity in the presence of as little as 1 nM rapamycin.

Context-specific synthetic T cell promoters from assembled transcriptional elements.

Genetic engineering of human lymphocytes for therapeutic applications is constrained by a lack of transgene transcriptional control, resulting in a compromised therapeutic index. Incomplete understanding of transcriptional logic limits the rational design of contextually responsive genetic modules1. Here, we juxtaposed rationally curated transcriptional response element (TRE) oligonucleotides by random concatemerization to generate a library from which we selected context-specific inducible synthetic promoters (iSynPros).

Locoregional CAR T cells for children with CNS tumors: Clinical procedure and catheter safety.

Central nervous system (CNS) tumors are the most common solid malignancy in the pediatric population. Based on adoptive cellular therapy's clinical success against childhood leukemia and the preclinical efficacy against pediatric CNS tumors, chimeric antigen receptor (CAR) T cells offer hope of improving outcomes for recurrent tumors and universally fatal diseases such as diffuse intrinsic pontine glioma (DIPG). However, a major obstacle for tumors of the brain and spine is ineffective T cell chemotaxis to disease sites.

Midterm Durability and Structural Valve Degeneration of Transcatheter Aortic Valve Replacement in a Federal Facility.

Objective: Transcatheter aortic valve replacement (TAVR), previously reserved for patients of intermediate to prohibitive surgical risk, has now been expanded to patients of any surgical risk with severe aortic stenosis. Bioprostheses are prone to structural valve degeneration (SVD), a progressive and multifactorial process that limits valve durability. As the population undergoing TAVR shifts toward a lower-risk and younger profile, long-term durability is a crucial determinant for patient outcomes.

Thymic adenocarcinoma presenting as an incidental mediastinal mass.

Background: Primary thymic adenocarcinoma represents an exceptionally rare malignancy, for which the cornerstone of therapy is margin-negative resection, with radiation and systemic therapy reserved for invasive and advanced disease. Thymic adenocarcinoma has not been previously reported in the setting of a concomitant malignancy, as reported herein.

Case Presentation: We present a case of a 55-year-old previously healthy male diagnosed with acute myeloid leukemia, also found to have a mediastinal mass.

Total anomalous origin of the coronary arteries from the pulmonary artery: a systematic review.

Background: Although rare, coronary artery anomalies can have significant clinical implications. Total anomalous origin of the coronary arteries from the pulmonary artery (TCAPA) represents a rare subtype of coronary artery anomaly for which little is known. The aim of this review was to characterise the presentation, utilised diagnostic modalities, associated cardiac lesions, and treatment strategies in patients with TCAPA.

Anomalous Origin of the Circumflex or Left Anterior Descending Artery From the Pulmonary Artery.

Anomalous origin of the circumflex or left anterior descending artery from the pulmonary artery (ACxAPA and ALADAPA, respectively) are rare congenital coronary anomalies with clinical presentation varying from an asymptomatic murmur to sudden cardiac arrest. A systematic review was performed, and 46 cases of ACxAPA and 51 cases of ALADAPA were identified in 87 articles. Data were collected and analyzed from each case.

Development of a porcine model of emergency resternotomy at a low-volume cardiac surgery centre.

Emergency resternotomy in the intensive care unit (ICU) is a rarely performed, yet potentially life-saving intervention. Success relies on recognition of a deteriorating clinical condition, timely deployment of equipment/personnel and rapid execution. Given how infrequently it is performed, we sought to develop a large animal model of resternotomy to prepare ICU nurses and technicians at our low-volume cardiac surgery military centre.

Recurrent Spontaneous Pneumothorax in a 47-Year-Old Woman.

Pneumothorax is a condition where air exists in the chest cavity, outside the lung. The causes of pneumothorax are numerous and determining the etiology can aid in treatment and prevent recurrence. We describe a 47-year-old female patient with past medical history of endometriosis who presented to the emergency room with recurrent right sided pneumothorax, its onset correlating with onset of menses.

Penetrating thoracic injury from a bean bag round complicated by development of post-operative empyema.

Bean bag guns were developed as a nonlethal means for law enforcement personnel to subdue individuals. The large surface area and lower velocities of the bean bag round theoretically result in transfer of most of the energy to the skin/subcutaneous tissue and minimize the likelihood of dermal penetration, thereby 'stunning' intended victims without causing injury to deeper structures. However, this technology has been associated with significant intra-abdominal and intrathoracic injuries, skin penetration and death.

Anomalous Origin of the Right Coronary Artery From the Pulmonary Artery: A Systematic Review.

Background: Anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA) is a rare congenital cardiac lesion that has been diagnosed in both children and adults with symptoms ranging from an asymptomatic murmur to sudden cardiac death. The aim of this review was to characterize published cases of ARCAPA to better understand this rare congenital coronary anomaly.

Methods: A systematic review was performed using PubMed, Embase, and Google Scholar for cases of ARCAPA.

Preclinical Evaluation of Bispecific Adaptor Molecule Controlled Folate Receptor CAR-T Cell Therapy With Special Focus on Pediatric Malignancies.

Chimeric antigen receptor (CAR)-T cell therapy has transformed pediatric oncology by producing high remission rates and potent effects in CD19+ B-cell malignancies. This scenario is ideal as CD19 expression is homogeneous and human blood provides a favorable environment for CAR-T cells to thrive and destroy cancer cells (along with normal B cells). Yet, CAR-T cell therapies for solid tumors remain challenged by fewer tumor targets and poor CAR-T cell performances in a hostile tumor microenvironment.

Cell-Templated Silica Microparticles with Supported Lipid Bilayers as Artificial Antigen-Presenting Cells for T Cell Activation.

Biomaterial properties that modulate T cell activation, growth, and differentiation are of significant interest in the field of cellular immunotherapy manufacturing. In this work, a new platform technology that allows for the modulation of various activation particle design parameters important for polyclonal T cell activation is presented. Artificial antigen presenting cells (aAPCs) are successfully created using supported lipid bilayers on various cell-templated silica microparticles with defined membrane fluidity and stimulating antibody density.

Macrophage silica nanoparticle response is phenotypically dependent.

Phagocytes are important players in host exposure to nanomaterials. Macrophages in particular are believed to be among the "first responders" and primary cell types that uptake and process nanoparticles, mediating host biological responses by subsequent interactions with inflammatory signaling pathways and immune cells. However, variations in local microenvironmental cues can significantly change the functional and phenotype of these cells, impacting nanoparticle uptake and overall physiological response.

A thermo-responsive protein treatment for dry eyes.

Millions of Americans suffer from dry eye disease, and there are few effective therapies capable of treating these patients. A decade ago, an abundant protein component of human tears was discovered and named lacritin (Lacrt). Lacrt has prosecretory activity in the lacrimal gland and mitogenic activity at the corneal epithelium.

Multimeric disintegrin protein polymer fusions that target tumor vasculature.

Recombinant protein therapeutics have increased in number and frequency since the introduction of human insulin, 25 years ago. Presently, proteins and peptides are commonly used in the clinic. However, the incorporation of peptides into clinically approved nanomedicines has been limited.