Validation of the graded prognostic assessment and recursive partitioning analysis as prognostic tools using a modern cohort of patients with brain metastases.

Background: Prognostic indices for patients with brain metastases (BM) are needed to individualize treatment and stratify clinical trials. Two frequently used tools to estimate survival in patients with BM are the recursive partitioning analysis (RPA) and the diagnosis-specific graded prognostic assessment (DS-GPA). Given recent advances in therapies and improved survival for patients with BM, this study aims to validate and analyze these 2 models in a modern cohort.

Alpha- to Beta-Cell Transdifferentiation in Neonatal Compared with Adult Mouse Pancreas in Response to a Modest Reduction in Beta-Cells Using Streptozotocin.

Following the near-total depletion of pancreatic beta-cells with streptozotocin (STZ), a partial recovery of beta-cell mass (BCM) can occur, in part due to the alpha- to beta-cell transdifferentiation with an intermediary insulin/glucagon bi-hormonal cell phenotype. However, human type 2 diabetes typically involves only a partial reduction in BCM and it is not known if recovery after therapeutic intervention involves islet cell transdifferentiation, or how this varies with age. Here, we used transgenic mouse models to examine if islet cell transdifferentiation contributes to BCM recovery following only a partial depletion of BCM.

Tumour-selective activity of RAS-GTP inhibition in pancreatic cancer.

Broad-spectrum RAS inhibition has the potential to benefit roughly a quarter of human patients with cancer whose tumours are driven by RAS mutations. RMC-7977 is a highly selective inhibitor of the active GTP-bound forms of KRAS, HRAS and NRAS, with affinity for both mutant and wild-type variants. More than 90% of cases of human pancreatic ductal adenocarcinoma (PDAC) are driven by activating mutations in KRAS.

Single-cell RNA sequencing comparison of the human metastatic prostate spine tumor microenvironment.

Spinal column tumors can be difficult to process for single-cell omic studies, given the heterogeneity in tissue. Here, we present a protocol for operating room-to-benchtop single-cell processing of clinical specimens from a prostate cancer patient. We describe steps for sample homogenization, red blood cell lysis, cryopreservation, and single-cell sequencing analysis.

Gender and Sex Differences in Health-related Quality of Life, Clinical Outcomes and Survival after Treatment of Metastatic Spine Disease.

Study Design: Retrospective review of prospective, multicenter and international cohort study.

Objective: To describe the effect of gender on HRQoL, clinical outcomes and survival for patients with spinal metastases treated with either surgery and/or radiation.

Summary Of Background Data: Gender differences in health-related outcomes are demonstrated in numerous studies, with women experiencing worse outcomes and receiving lower standards of care than men, however, the influence that gender has on low health-related quality of life (HRQoL) and clinical outcomes after spine surgery remains unclear.

Tumor Explants Elucidate a Cascade of Paracrine SHH, WNT, and VEGF Signals Driving Pancreatic Cancer Angiosuppression.

Unlabelled: The sparse vascularity of pancreatic ductal adenocarcinoma (PDAC) presents a mystery: What prevents this aggressive malignancy from undergoing neoangiogenesis to counteract hypoxia and better support growth? An incidental finding from prior work on paracrine communication between malignant PDAC cells and fibroblasts revealed that inhibition of the Hedgehog (HH) pathway partially relieved angiosuppression, increasing tumor vascularity through unknown mechanisms. Initial efforts to study this phenotype were hindered by difficulties replicating the complex interactions of multiple cell types in vitro. Here we identify a cascade of paracrine signals between multiple cell types that act sequentially to suppress angiogenesis in PDAC.

Association Between Urbanicity and Outcomes Among Patients with Spinal Cord Ependymomas in the United States.

Background: Spinal cord ependymomas (SCEs) represent the most common intramedullary spinal cord tumors among adults. Research shows that access to neurosurgical care and patient outcomes can be greatly influenced by patient location. This study investigates the association between the outcomes of patients with SCE in metropolitan and nonmetropolitan areas.

Associations between urbanicity and spinal cord astrocytoma management and outcomes.

Background: The management of spinal cord astrocytomas (SCAs) remains controversial and may include any combination of surgery, radiation, and chemotherapy. Factors such as urbanicity (metropolitan versus non-metropolitan residence) are shown to be associated with patterns of treatment and clinical outcomes in a variety of cancers, but the role urbanicity plays in SCA treatment remains unknown.

Methods: The Central Brain Tumor Registry of the United States (CBTRUS) analytic dataset, which combines data from CDC's National Program of Cancer Registries (NPCR) and NCI's Surveillance, Epidemiology, and End Results Programs, was used to identify individuals with SCAs between 2004 and 2019.

Prophylactic Muscle Flaps Decrease Wound Complication Rates in Patients with Oncologic Spine Disease.

Background: Patients with oncologic spine disease face a high systemic illness burden and often require surgical intervention to alleviate pain and maintain spine stability. Wound healing complications are the most common reason for reoperation in this population and are known to impact quality of life and initiation of adjuvant therapy. Prophylactic muscle flap (MF) closure is known to reduce wound healing complications in high-risk patients; however, the efficacy in oncologic spine patients is not well established.

Fatal Epileptic Seizures in Mice Having Compromised Glutathione and Ascorbic Acid Biosynthesis.

Reduced glutathione (GSH) and ascorbic acid (AA) are the two most abundant low-molecular-weight antioxidants in mammalian tissues. knockout mice lack the gene encoding the modifier subunit of the rate-limiting enzyme in GSH biosynthesis; mice exhibit 10-40% of normal tissue GSH levels and show no overt phenotype. knockout mice, lacking a functional gene encoding L-gulono-γ-lactone oxidase, cannot synthesize AA and depend on dietary ascorbic acid for survival.

Racial disparities in inpatient clinical presentation, treatment, and outcomes in brain metastasis.

Background: Few studies have assessed the impact of race on short-term patient outcomes in the brain metastasis population. The goal of this study is to evaluate the association of race with inpatient clinical presentation, treatment, in-hospital complications, and in-hospital mortality rates for patients with brain metastases (BM).

Method: Using data collected from the National Inpatient Sample between 2004 and 2014, we retrospectively identified adult patients with a primary diagnosis of BM.

Identification and Optimization of a Ligand-Efficient Benzoazepinone Bromodomain and Extra Terminal (BET) Family Acetyl-Lysine Mimetic into the Oral Candidate Quality Molecule I-BET432.

The bromodomain and extra terminal (BET) family of proteins are an integral part of human epigenome regulation, the dysregulation of which is implicated in multiple oncology and inflammatory diseases. Disrupting the BET family bromodomain acetyl-lysine (KAc) histone protein-protein interaction with small-molecule KAc mimetics has proven to be a disease-relevant mechanism of action, and multiple molecules are currently undergoing oncology clinical trials. This work describes an efficiency analysis of published GSK pan-BET bromodomain inhibitors, which drove a strategic choice to focus on the identification of a ligand-efficient KAc mimetic with the hypothesis that lipophilic efficiency could be drastically improved during optimization.

Exercise-induced engagement of the IL-15/IL-15Rα axis promotes anti-tumor immunity in pancreatic cancer.

Aerobic exercise is associated with decreased cancer incidence and cancer-associated mortality. However, little is known about the effects of exercise on pancreatic ductal adenocarcinoma (PDA), a disease for which current therapeutic options are limited. Herein, we show that aerobic exercise reduces PDA tumor growth, by modulating systemic and intra-tumoral immunity.

Use of Nucleic Acid Amplification Testing for Rapid Detection of Complex Among US Tuberculosis Patients, 2011‒2017.

Background: Nucleic acid amplification (NAA) tests rapidly detect complex directly from clinical specimens, providing valuable results for those evaluated for tuberculosis.

Methods: We analyzed characteristics of cases with NAA testing performed, compared cases with positive and negative NAA test results, and calculated turnaround time and time to treatment for all verified cases reported to the National Tuberculosis Surveillance System in the United States during 2011-2017.

Results: Among 67082 verified tuberculosis cases with NAA testing information, 30820 (45.

Pretransplant physical frailty, postoperative delirium, and short-term outcomes among older lung transplant recipients.

Purpose: Delirium is a common, complex medical challenge that faces surgical patients in the postoperative period. Patients undergoing lung transplantation are at especially high risk given their predisposition to physical frailty and prolonged hospitalization. We sought to investigate the relationship between physical frailty, delirium, and short-term lung transplantation outcomes.

Home-Based Hematopoietic Cell Transplantation in the United States.

Patients undergoing allogeneic (allo) and autologous (auto) hematopoietic cell transplantation (HCT) require extensive hospitalizations or daily clinic visits for the duration of their transplantation. Home HCT, wherein patients live at home and providers make daily trips to the patient's residence to perform assessments and deliver any necessary interventions, may enhance patient quality of life and improve outcomes. We conducted the first study of home HCT in the United States to evaluate this model in the US healthcare setting and to determine the effect on clinical outcomes and quality of life.

Robotic navigation in spine surgery: Where are we now and where are we going?

Robotic navigation is a new and rapidly emerging niche within minimally invasive spine surgery. The robotic arms-race began in 2004 and has resulted in no less than four major robotic surgical adjuncts. Current Food and Drug Administration (FDA)-approved applications of robotic navigation are limited to pedicle screw instrumentation, but new indications and experimental applications are rapidly emerging.

Robotic-Assisted Trajectory Into Kambin's Triangle During Percutaneous Transforaminal Lumbar Interbody Fusion-Initial Case Series Investigating Safety and Efficacy.

Background: Minimally invasive spine surgery (MISS) has the potential to further advance with the use of robot-assisted (RA) techniques. While RA pedicle screw placement has been extensively investigated, there is a lack of literature on the use of the robot for other tasks, such as accessing Kambin's triangle in percutaneous lumbar interbody fusion (percLIF).

Objective: To characterize the surgical feasibility and preliminary outcomes of an initial case series of 10 patients receiving percLIF with RA cage placement via Kambin's triangle.

Risk factors for prolonged length of stay in patients undergoing surgery for intramedullary spinal cord tumors.

Unlabelled: Primary spine tumors are rare neoplasms that affect about 0.62 per 100,000 individuals in the US. Intramedullary spinal cord tumors (IMSCTs) are the rarest of all primary tumors involving the spine and can cause pain, imbalance, urinary dysfunction and neurological deficits.

Animal Models of Metastatic Lesions to the Spine: A Focus on Epidural Spinal Cord Compression.

Epidural spinal cord compression (ESCC) secondary to spine metastases is one of the most devastating sequelae of primary cancer as it may lead to muscle weakness, paresthesia, pain, and paralysis. Spine metastases occur through a multistep process that can result in eventual ESCC; however, the lack of a preclinical model to effectively recapitulate each step of this metastatic cascade and the symptom burden of ESCC has limited our understanding of this disease process. In this review, we discuss animal models that best recapitulate ESCC.