Microenvironment actuated CAR T cells improve solid tumor efficacy without toxicity.

A major limiting factor in the success of chimeric antigen receptor (CAR) T cell therapy for the treatment of solid tumors is targeting tumor antigens also found on normal tissues. CAR T cells against GD2 induced rapid, fatal neurotoxicity because of CAR recognition of GD2 normal mouse brain tissue. To improve the selectivity of the CAR T cell, we engineered a synthetic Notch receptor that selectively expresses the CAR upon binding to P-selectin, a cell adhesion protein overexpressed in tumor neovasculature.

A robust benchmark for detecting low-frequency variants in the HG002 Genome In A Bottle NIST reference material.

Somatic mosaicism is an important cause of disease, but mosaic and somatic variants are often challenging to detect because they exist in only a fraction of cells. To address the need for benchmarking subclonal variants in normal cell populations, we developed a benchmark containing mosaic variants in the Genome in a Bottle Consortium (GIAB) HG002 reference material DNA from a large batch of a normal lymphoblastoid cell line. First, we used a somatic variant caller with high coverage (300x) Illumina whole genome sequencing data from the Ashkenazi Jewish trio to detect variants in HG002 not detected in at least 5% of cells from the combined parental data.

Comprehensive genome analysis and variant detection at scale using DRAGEN.

Research and medical genomics require comprehensive, scalable methods for the discovery of novel disease targets, evolutionary drivers and genetic markers with clinical significance. This necessitates a framework to identify all types of variants independent of their size or location. Here we present DRAGEN, which uses multigenome mapping with pangenome references, hardware acceleration and machine learning-based variant detection to provide insights into individual genomes, with ~30 min of computation time from raw reads to variant detection.

Identification of allele-specific KIV-2 repeats and impact on Lp(a) measurements for cardiovascular disease risk.

The abundance of Lp(a) protein holds significant implications for the risk of cardiovascular disease (CVD), which is directly impacted by the copy number (CN) of KIV-2, a 5.5 kbp sub-region. KIV-2 is highly polymorphic in the population and accurate analysis is challenging.

Multi-modality imaging parameters that predict rapid tumor regression in head and neck radiotherapy.

Background And Purpose: Volume regression during radiotherapy can indicate patient-specific treatment response. We aimed to identify pre-treatment multimodality imaging (MMI) metrics from positron emission tomography (PET), magnetic resonance imaging (MRI), and computed tomography (CT) that predict rapid tumor regression during radiotherapy in human papilloma virus (HPV) associated oropharyngeal carcinoma.

Materials And Methods: Pre-treatment FDG PET-CT, diffusion-weighted MRI (DW-MRI), and intra-treatment (at 1, 2, and 3 weeks) MRI were acquired in 72 patients undergoing chemoradiation therapy for HPV+ oropharyngeal carcinoma.

Auto-segmentation of neck nodal metastases using self-distilled masked image transformer on longitudinal MR images.

Objectives: Auto-segmentation promises greater speed and lower inter-reader variability than manual segmentations in radiation oncology clinical practice. This study aims to implement and evaluate the accuracy of the auto-segmentation algorithm, "Masked Image modeling using the vision Transformers (SMIT)," for neck nodal metastases on longitudinal T-weighted (Tw) MR images in oropharyngeal squamous cell carcinoma (OPSCC) patients.

Methods: This prospective clinical trial study included 123 human papillomaviruses (HPV-positive [+]) related OSPCC patients who received concurrent chemoradiotherapy.

Comprehensive and accurate genome analysis at scale using DRAGEN accelerated algorithms.

Research and medical genomics require comprehensive and scalable solutions to drive the discovery of novel disease targets, evolutionary drivers, and genetic markers with clinical significance. This necessitates a framework to identify all types of variants independent of their size (e.g.

Concurrent carboplatin and paclitaxel definitive radiation therapy for locally advanced head and neck cancer.

Background: We report the outcomes of cisplatin-ineligible HNSCC patients treated with definitive chemoradiation and concurrent carboplatin and paclitaxel.

Materials And Methods: We included consecutive HNSCC patients treated from 2013 to 2021 that received definitive chemoradiation with carboplatin and paclitaxel. Locoregional recurrences (LRR) and distant metastases (DM) were estimated using cumulative incidence functions.

Change of mortality of patients with acute ischemic stroke before and after 2015.

Introduction: Advances in the diagnosis and management of acute ischemic stroke (AIS) and the increased use of mechanical thrombectomy (MT) have improved the quality of care and prognosis of patients with AIS since 2015. We investigated the changing trends in mortality of patients with AIS in Korea before and after 2015.

Materials And Methods: A retrospective cohort study was conducted using combined anonymized data from the Acute Stroke Assessment Registry of Korea and the Health Insurance Review & Assessment Service database.

Proton Therapy Outcomes for Head and Neck Cutaneous Melanoma: Proton Collaborative Group Analysis.

Purpose: Reports of proton beam therapy (PBT) utilization for cutaneous melanoma of the head and neck (HN) region is virtually non-existent. This study reports on the efficacy and acute toxicities of PBT for primary HN cutaneous melanoma.

Materials And Methods: We queried the prospectively collected, multi-institutional Proton Collaborative Group registry for all consecutive patients with HN cutaneous melanoma receiving PBT from May 2010 to December 2019.

Short- and long-term mortality of subarachnoid hemorrhage according to hospital volume and severity using a nationwide multicenter registry study.

Introduction: Recent improvements in treatment for subarachnoid hemorrhage (SAH) have decreased the mortality rates; however, the outcomes of SAH management are dependent on many other factors. In this study, we used nationwide, large-scale, observational data to investigate short- and long-term mortality rates after SAH treatment and the influence of patient severity and hospital volume.

Patients And Methods: We selected patients with SAH treated with clipping and coiling from the South Korean Acute Stroke Assessment Registry.

Hospital Lawsuits Over Unpaid Bills Increased By 37 Percent In Wisconsin From 2001 To 2018.

We analyzed Wisconsin court records from the period 2001-18 to document trends in hospital lawsuits to recover patients' unpaid medical bills. These lawsuits increased 37 percent during this period, from 1.12 per 1,000 residents in 2001 to 1.

Metastatic Testicular Embryonal Carcinoma Presenting as Gastrointestinal Hemorrhage.

Testicular cancer is the most common malignancy in men aged 20-35 years, usually presenting with painless scrotal swelling. Metastases, should they occur, frequently involve retroperitoneal lymph nodes, which drain the testes. Gastrointestinal (GI) metastases are rare, and metastatic disease may not initially be considered in a young man presenting with GI hemorrhage.

Optimal surgical timing and radiotherapy dose for trimodality therapy in locally advanced non-small cell lung cancer.

Purpose/objectives: Data are conflicting on the effects of time interval from neoadjuvant chemoradiation (NCRT) to surgery for locally advanced non-small-cell lung cancer (LA-NSCLC). This study investigated the impact of surgical timing after NCRT and radiation dose on postoperative mortality and overall survival (OS).

Materials And Methods: Using the National Cancer Database, we identified 3489 LA-NSCLC patients treated with NCRT and surgery.

Brachytherapy of the head and neck: An University of California Los Angeles guide to morbidity reduction.

The head and neck (H&N) region is among the most intricate and functional part of our anatomy. Major functional nerves and blood vessels with importance that affect the entire body emanate from the base of skull. Brachytherapy plays an important role as a single modality therapy in early cancer of the lip and oral cavity and a supplemental role in the pharynx or in advanced or recurrent disease.

Interactions Between Enhanced Polygenic Risk Scores and Lifestyle for Cardiovascular Disease, Diabetes, and Lipid Levels.

Background: Both lifestyle and genetic factors confer risk for cardiovascular diseases, type 2 diabetes, and dyslipidemia. However, the interactions between these 2 groups of risk factors were not comprehensively understood due to previous poor estimation of genetic risk. Here we set out to develop enhanced polygenic risk scores (PRS) and systematically investigate multiplicative and additive interactions between PRS and lifestyle for coronary artery disease, atrial fibrillation, type 2 diabetes, total cholesterol, triglyceride, and LDL-cholesterol.

Treatment interruptions affect biochemical failure rates in prostate cancer patients treated with proton beam therapy: Report from the multi-institutional proton collaborative group registry.

Introduction: To date, no studies examining the effect of treatment interruptions (TI) with proton beam therapy (PBT) have been published. The goal of our study was to determine the predictors of TI amongst patients with prostate cancer (PCa) treated with PBT and to determine whether TI are associated with biochemical failure (BF). We hypothesized that any correlation between TI and biochemical control would be more pronounced in high risk groups.

Oral IBGard™ Before Colonoscopy: A Single-Center Double-Blinded, Randomized, Placebo-Controlled Trial.

Background: Peppermint oil is well known to inhibit smooth muscle contractions, and its topical administration during colonoscopy is reported to reduce colonic spasms.

Aims: We aimed to assess whether oral administration of IBGard™, a sustained-release peppermint oil formulation, before colonoscopy reduces spasms and improves adenoma detection rate (ADR).  METHODS: We performed a single-center randomized, double-blinded, placebo-controlled trial.

Intestinal Tuberculosis Masquerading as Crohn's Disease? A Case of Disseminated Tuberculosis after Anti-TNF Therapy for Suspected Crohn's Disease.

Intestinal tuberculosis (ITB) and Crohn's disease (CD) very closely resemble each other in symptomatology, imaging, appearance, and pathology. While ITB is rare in the United States, its prevalence is significantly higher in endemic areas, thus presenting a diagnostic dilemma in immigrant populations from high-risk countries. This patient was diagnosed with CD and treated with anti-TNF agents after indeterminate screening for latent tuberculosis.

Neoadjuvant chemotherapy improves survival compared with concurrent chemoradiation alone in nasopharyngeal carcinoma patients with N3 disease.

Background: Neoadjuvant chemotherapy (NAC) trials in endemic regions of nasopharyngeal carcinoma (NPC) found improved survival, but studies are lacking in nonendemic regions. We assessed whether adding NAC to concurrent chemoradiation (CRT) improves overall survival (OS), especially in high-risk nonendemic patients.

Methods: Definitively treated NPC patients (n = 5424) from the National Cancer Database were analyzed for predictors of NAC and NAC effects on OS with multivariate Cox proportional hazards analysis (multivariate analysis [MVA]).

Hemobilia: Etiology, diagnosis, and treatment.

Hemobilia refers to bleeding from and/or into the biliary tract and is an uncommon but important cause of gastrointestinal hemorrhage. Reports of hemobilia date back to the 1600s, but due to its relative rarity and challenges in diagnosis, only in recent decades has hemobilia been more critically studied. The majority of cases of hemobilia are iatrogenic and caused by invasive procedures involving the liver, pancreas, bile ducts and/or the hepatopancreatobiliary vasculature, with trauma and malignancy representing the two other leading causes.