Hu8F4-CAR T cells with mutated Fc spacer segment improve target specificity and mediate anti-leukemia activity in vivo.

Background Aims: Hu8F4 is a T-cell receptor-like antibody with high affinity for the leukemia-associated antigen PR1/HLA-A2 epitope. Adapted into a chimeric antigen receptor (CAR) format, Hu8F4-CAR is composed of the Hu8F4 single-chain variable fragment, the human IgG1 CH2CH3 extracellular spacer domain, a human CD28 costimulatory domain and the human CD3ζ signaling domain. We have demonstrated high efficacy of Hu8F4-CAR-T cells against PR1/HLA-A2-expressing cell lines and leukemic blasts from patients with acute myeloid leukemia in vitro.

Determination of the Optimal Volume of 0.5% Ropivacaine in Single-injection Retroclavicular Brachial Plexus Block for Arthroscopic Shoulder Surgery: A Phase I/II Trial.

Background: A brachial plexus block plays an important role in providing perioperative analgesia for shoulder surgery; however, the inherent risk of phrenic nerve block and resulting hemidiaphragmatic paralysis may limit its use in patients with compromised pulmonary function. This study aimed to evaluate the safety, efficacy, maximum tolerated volume, and optimal biologic volume of 0.5% ropivacaine used in a single-injection retroclavicular brachial plexus block for arthroscopic shoulder surgery.

Effects of Recombinant α-Microglobulin on Early Proteomic Response in Risk Organs after Exposure to Lu-Octreotate.

Recombinant α-microglobulin (A1M) is proposed as a protector during Lu-octreotate treatment of neuroendocrine tumors, which is currently limited by bone marrow and renal toxicity. Co-administration of Lu-octreotate and A1M could result in a more effective treatment by protecting healthy tissue, but the radioprotective action of A1M is not fully understood. The aim of this study was to examine the proteomic response of kidneys and bone marrow early after Lu-octreotate and/or A1M administration.

Cefiderocol heteroresistance associated with mutations in TonB-dependent receptor genes in of clinical origin.

The siderophore-cephalosporin cefiderocol (FDC) presents a promising treatment option for carbapenem-resistant (CR) (PA). FDC circumvents traditional porin and efflux-mediated resistance by utilizing TonB-dependent receptors (TBDRs) to access the periplasmic space. Emerging FDC resistance has been associated with loss of function mutations within TBDR genes or the regulatory genes controlling TBDR expression.

Inulin-gel-based oral immunotherapy remodels the small intestinal microbiome and suppresses food allergy.

Despite the potential of oral immunotherapy against food allergy, adverse reactions and loss of desensitization hinder its clinical uptake. Dysbiosis of the gut microbiota is implicated in the increasing prevalence of food allergy, which will need to be regulated to enable for an effective oral immunotherapy against food allergy. Here we report an inulin gel formulated with an allergen that normalizes the dysregulated ileal microbiota and metabolites in allergic mice, establishes allergen-specific oral tolerance and achieves robust oral immunotherapy efficacy with sustained unresponsiveness in food allergy models.

Vessel-targeted compensation of deformable motion in interventional cone-beam CT.

The present standard of care for unresectable liver cancer is transarterial chemoembolization (TACE), which involves using chemotherapeutic particles to selectively embolize the arteries supplying hepatic tumors. Accurate volumetric identification of intricate fine vascularity is crucial for selective embolization. Three-dimensional imaging, particularly cone-beam CT (CBCT), aids in visualization and targeting of small vessels in such highly variable anatomy, but long image acquisition time results in intra-scan patient motion, which distorts vascular structures and tissue boundaries.

Impact of isotype on the mechanism of action of agonist anti-OX40 antibodies in cancer: implications for therapeutic combinations.

Background: OX40 has been widely studied as a target for immunotherapy with agonist antibodies taken forward into clinical trials for cancer where they are yet to show substantial efficacy. Here, we investigated potential mechanisms of action of anti-mouse (m) OX40 and anti-human (h) OX40 antibodies, including a clinically relevant monoclonal antibody (mAb) (GSK3174998) and evaluated how isotype can alter those mechanisms with the aim to develop improved antibodies for use in rational combination treatments for cancer.

Methods: Anti-mOX40 and anti-hOX40 mAbs were evaluated in a number of in vivo models, including an OT-I adoptive transfer immunization model in hOX40 knock-in (KI) mice and syngeneic tumor models.

METTL3-mediated chromatin contacts promote stress granule phase separation through metabolic reprogramming during senescence.

METTL3 is the catalytic subunit of the methyltransferase complex, which mediates mA modification to regulate gene expression. In addition, METTL3 regulates transcription in an enzymatic activity-independent manner by driving changes in high-order chromatin structure. However, how these functions of the methyltransferase complex are coordinated remains unknown.

Etiology of hospital mortality in children living in low- and middle-income countries: a systematic review and meta-analysis.

In 2019, 80% of the 7.4 million global child deaths occurred in low- and middle-income countries (LMICs). Global and regional estimates of cause of hospital death and admission in LMIC children are needed to guide global and local priority setting and resource allocation but are currently lacking.

Chidamide combined with a modified Bu-Cy conditioning regimen improves survival in patients with T-cell acute lymphoblastic leukemia/lymphoma undergoing allogeneic hematopoietic stem cell transplantation.

This study aimed to evaluate the efficacy and safety of chidamide (Chi) combined with a modified Busulfan-Cyclophosphamide (mBuCy) conditioning regimen for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Twenty-two patients received chidamide combined with mBuCy conditioning regimen (Chi group). A matched-pair control (CON) group of 44 patients (matched 1:2) received mBuCy only in the same period.

Total Neoadjuvant Therapy for Rectal Cancer: Which Regimens to Use?

Total neoadjuvant therapy (TNT) is a novel strategy for rectal cancer that administers both (chemo)radiotherapy and systemic chemotherapy before surgery. TNT is expected to improve treatment compliance, tumor regression, organ preservation, and oncologic outcomes. Multiple TNT regimens are currently available with various combinations of the treatments including induction or consolidation chemotherapy, triplet or doublet chemotherapy, and long-course chemoradiotherapy or short-course radiotherapy.

Surgical Management of High-Grade Meningiomas.

Maximal resection with the preservation of neurological function are the mainstays of the surgical management of high-grade meningiomas. Surgical morbidity is strongly associated with tumor size, location, and invasiveness, whereas patient survival is strongly associated with the extent of resection, tumor biology, and patient health. A versatile microsurgical skill set combined with a cogent multimodality treatment plan is critical in order to achieve optimal patient outcomes.

Self-management intervention improves patient adherence to swallowing exercises during radiation for head and neck cancer.

Background: While preventive swallowing exercises reduce the risk of radiation-associated dysphagia in patients with head and neck cancer, strategies are needed to improve patient adherence.

Methods: Before radiation, all participants were taught preventive swallowing exercises and randomized to either an adherence intervention or enhanced usual care. During radiation, all participants met twice with a speech pathologist for swallowing assessment and reinforcement of exercises.

Oral Pre-malignancy: An Update on Novel Therapeutic Approaches.

Purpose Of Review: This review aims to provide a comprehensive overview of the current advances in managing and preventing progression of oral potentially malignant disorders (OPMDs), focusing on their histological and clinicopathological features, and management.

Recent Findings: Recent studies, including a multicenter cross-sectional study, have identified oral leukoplakia as the most prevalent form of OPMD, comprising over half of the cases examined. Advances in histological grading, specifically the World Health Organization's three-tier system (mild, moderate, and severe dysplasia), have significantly enhanced the accuracy of risk assessment for malignant transformation.

Bayesian Learning of Personalized Longitudinal Biomarker Trajectory.

This work concerns the effective personalized prediction of longitudinal biomarker trajectory, motivated by a study of cancer targeted therapy for patients with chronic myeloid leukemia (CML). Continuous monitoring with a confirmed biomarker of residual disease is a key component of CML management for early prediction of disease relapse. However, the longitudinal biomarker measurements have highly heterogeneous trajectories between subjects (patients) with various shapes and patterns.

Colorectal carcinoma cell targeting aromatherapy with Teucrium ramosissimum essential oil to sensitize TRAIL/Apo2L-induced HCT-116 cell death.

This report drives insights for the investigation of the underlying mechanisms of antitumor effects of Teucrium ramosissimum (TrS) essential oil (EO) that elicits colon tumor protection via activation of cell death machinery. A study of the aerial part phytocomplex was performed by FTIR spectra and GC/MS. In vivo colon carcinogenesis induced by LPS was carried out using mouse model.

Free fibula mandible reconstruction for osteoradionecrosis is more challenging than for primary cancer.

Introduction: Osteoradionecrosis (ORN) of the mandible is an unfortunate potential sequela of radiotherapy for head and neck cancer. In advanced cases of ORN, mandibulectomy, and free fibula flap reconstruction are required. We hypothesized that patients undergoing fibula free flap reconstruction and mandibulectomy for ORN pose unique challenges and experience more complications than patients undergoing fibula free flaps after oncologic mandibulectomy.

Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma.

Background: Bortezomib, lenalidomide, and dexamethasone (VRd) is a preferred first-line treatment option for patients with newly diagnosed multiple myeloma. Whether the addition of the anti-CD38 monoclonal antibody isatuximab to the VRd regimen would reduce the risk of disease progression or death among patients ineligible to undergo transplantation is unclear.

Methods: In an international, open-label, phase 3 trial, we randomly assigned, in a 3:2 ratio, patients 18 to 80 years of age with newly diagnosed multiple myeloma who were ineligible to undergo transplantation to receive either isatuximab plus VRd or VRd alone.