Prognostic significance of immune reconstitution following CD19 CAR T-cell therapy for relapsed/refractory B-cell lymphoma.

Immune deficits after CD19 chimeric antigen receptor (CAR) T-cell therapy can be long-lasting, predisposing patients to infections and non-relapse mortality. In B-cell non-Hodgkin lymphoma (B-NHL), the prognostic impact of immune reconstitution (IR) remains ill-defined, and detailed cross-product comparisons have not been performed to date. In this retrospective observational study, we longitudinally characterized lymphocyte subsets and immunoglobulin levels in 105 B-NHL patients to assess patterns of immune recovery arising after CD19 CAR-T.

Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges.

Loss of Kmt2c or Kmt2d primes urothelium for tumorigenesis and redistributes KMT2A-menin to bivalent promoters.

Members of the KMT2C/D-KDM6A complex are recurrently mutated in urothelial carcinoma and in histologically normal urothelium. Here, using genetically engineered mouse models, we demonstrate that Kmt2c/d knockout in the urothelium led to impaired differentiation, augmented responses to growth and inflammatory stimuli and sensitization to oncogenic transformation by carcinogen and oncogenes. Mechanistically, KMT2D localized to active enhancers and CpG-poor promoters that preferentially regulate the urothelial lineage program and Kmt2c/d knockout led to diminished H3K4me1, H3K27ac and nascent RNA transcription at these sites, which leads to impaired differentiation.

Combining a WT1 Vaccine (Galinpepimut-S) With Checkpoint Inhibition (Nivolumab) in Patients With WT1-Expressing Diffuse Pleural Mesothelioma: A Phase 1 Study.

Introduction: WT1 often presents on the surface of diffuse pleural mesotheliomas (DPMs) and is an ideal therapeutic target. Galinpepimut-S (GPS), a tetravalent, non-human leukocyte antigen-restricted, heteroclitic WT1-specific peptide vaccine was safe and effective in early phase clinical trials and upregulates T-cell suppressive programmed death-ligand 1 in the tumor microenvironment of other malignancies. A randomized phase 2 study of adjuvant GPS in patients with DPM trended toward improved median overall survival.

Brief Report: Clinical Characteristics and Outcomes of Patients With Thoracic SMARCA4-Deficient Undifferentiated Tumors.

Introduction: Thoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UTs) are a recently defined group of aggressive cancers in which the effectiveness of standard treatments for lung cancer is unknown.

Methods: We collected clinical, pathologic, and demographic variables from five institutions for patients whose tumors met criteria for SMARCA4-UTs (undifferentiated phenotype and loss of SMARCA4 (BRG1) by immunohistochemistry).

Results: We identified 92 patients with SMARCA4-UTs; 58 (63%) had stage IV disease at diagnosis and 16 (17%) developed recurrent or metastatic disease after initial diagnosis.

Effects of a Revision to the Standard Admission Order Set on Laxative Prescribing for Opioid-Induced Constipation.

Purpose: Opioid-induced constipation (OIC) is highly prevalent in patients with cancer-related pain on opioid analgesics and has negative consequences on physical and psychological well-being and quality of life. Oncology clinical practice guidelines recommend the use of osmotic and stimulant laxatives for the prevention and management of opioid-induced constipation, not stool softeners such as docusate sodium. Prescribing practices continue to fall behind these recommendations.

SGLT2i and Primary Prevention of Cancer Therapy-Related Cardiac Dysfunction in Patients With Diabetes.

Background: Specific cancer treatments can lead to cancer therapy-related cardiac dysfunction (CTRCD). Sodium glucose cotransporter-2 inhibitors (SGLT2is) can potentially prevent these cardiotoxic effects.

Objectives: This study sought to determine whether SGLT2i use is associated with a lower incidence of CTRCD in patients with type 2 diabetes mellitus (T2DM) and cancer, exposed to potentially cardiotoxic antineoplastic agents, and without a prior documented history of cardiomyopathy or heart failure.

Cardiovascular Considerations During Cancer Therapy: Gaps in Evidence and Expert Panel Recommendations.

The administration of certain cancer therapies can be associated with the development of cardiovascular toxicity or complications. This spectrum of toxicities is broad and requires nuanced approaches for prevention, identification, and management. This expert panel summarizes the consensus of opinions of diverse health care professionals in several key areas: 1) cardioprotection involves strategies aimed at the primary prevention of cancer therapy-related cardiovascular toxicity; 2) surveillance entails monitoring for cancer therapy-related cardiovascular toxicity during cancer therapy; 3) permissive cardiotoxicity is the informed continuation of cancer therapy in the presence of cardiovascular toxicity, along with the implementation of mitigating cardiovascular treatments; and 4) special considerations include the invasive management of severe cardiovascular disease in patients receiving treatments for advanced cancer and the exploration of drug-drug interactions in cardio-oncology.

Overview of Molecular Prognostication for Common Solid Tumor Histologies - What the Surgeon Should Know.

Study Design: Narrative Literature review.

Objective: To provide a general overview of important molecular markers and targeted therapies for the most common neoplasms (lung, breast, prostate and melanoma) that metastasize to the spine and offer guidance on how to best incorporate them in the clinical setting.

Methods: A narrative review of the literature was performed using PubMed, Google Scholar, Medline databases, as well as the histology-specific National Comprehensive Cancer Network guidelines to identify relevant articles limited to the English language.

Defining Spine Cancer Pain Syndromes: A Systematic Review and Proposed Terminology.

Study Design: Systematic Review.

Objectives: Formalized terminology for pain experienced by spine cancer patients is lacking. The common descriptors of spine cancer pain as mechanical or non-mechanical is not exhaustive.

Enhanced Recovery After Surgery for patients undergoing radical cystectomy: Surgeons' perspectives and recommendations ten years after its implementation.

Background And Objectives: Enhanced Recovery After Surgery (ERAS) guidelines for Radical Cystectomy (RC) were published over ten years ago. Aim of this systematic review is to update ERAS recommendations for patients undergoing RC and to give an expert opinion on the relevance of each single ERAS item.

Methods: A systematic review was performed to identify the impact of each single ERAS item on RC outcomes.

Automatic medical imaging segmentation via self-supervising large-scale convolutional neural networks.

Purpose: This study aims to develop a robust, large-scale deep learning model for medical image segmentation, leveraging self-supervised learning to overcome the limitations of supervised learning and data variability in clinical settings.

Methods And Materials: We curated a substantial multi-center CT dataset for self-supervised pre-training using masked image modeling with sparse submanifold convolution. We designed a series of Sparse Submanifold U-Nets (SS-UNets) of varying sizes and performed self-supervised pre-training.

Durvalumab with or without bevacizumab with transarterial chemoembolisation in hepatocellular carcinoma (EMERALD-1): a multiregional, randomised, double-blind, placebo-controlled, phase 3 study.

Background: Transarterial chemoembolisation (TACE) is standard of care for patients with unresectable hepatocellular carcinoma that is amenable to embolisation; however, median progression-free survival is still approximately 7 months. We aimed to assess whether adding durvalumab, with or without bevacizumab, might improve progression-free survival.

Methods: In this multiregional, randomised, double-blind, placebo-controlled, phase 3 study (EMERALD-1), adults aged 18 years or older with unresectable hepatocellular carcinoma amenable to embolisation, an Eastern Cooperative Oncology Group performance status of 0 or 1 at enrolment, and at least one measurable intrahepatic lesion per modified Response Evaluation Criteria in Solid Tumours (RECIST) were enrolled at 157 medical sites including research centres and general and specialist hospitals in 18 countries.

Ovarian cancer staging and follow-up: updated guidelines from the European Society of Urogenital Radiology female pelvic imaging working group.

Objective: To provide up-to-date European Society of Urogenital Radiology (ESUR) guidelines for staging and follow-up of patients with ovarian cancer (OC).

Methods: Twenty-one experts, members of the female pelvis imaging ESUR subcommittee from 19 institutions, replied to 2 rounds of questionnaires regarding imaging techniques and structured reporting used for pre-treatment evaluation of OC patients. The results of the survey were presented to the other authors during the group's annual meeting.

The Society of Thoracic Surgeons (STS) Clinical Practice Guideline on Surgical Management of Oligometastatic Non-small Cell Lung Cancer.

Background: The use of local consolidative therapy (LCT) in patients with oligometastatic non-small cell lung cancer (NSCLC) is rapidly evolving, with a preponderance of data supporting the benefits of such therapeutic approaches incorporating pulmonary resection for appropriately selected candidates. However, practices vary widely institutionally and regionally, and evidence-based guidelines are lacking.

Methods: The Society of Thoracic Surgeons assembled a panel of thoracic surgical oncologists to evaluate and synthesize the available evidence regarding the role of pulmonary resection as LCT.

Abnormal p53 High-Grade Endometrioid Endometrial Cancer: A Systematic Review and Meta-Analysis.

Objective: Our primary objective was to evaluate the oncologic outcomes of patients with abnormal p53 FIGO grade 3 (high-grade) endometrioid endometrial cancer. As secondary objectives, we determined the global prevalence of abnormal p53 in grade 3 endometrioid endometrial carcinomas and the geographical variations.

Methods: The following electronic databases were searched: PubMed/Medline, EMBASE, Cochrane Library, Scopus, and Web of Science.

Chronic obstructive pulmonary disease: A narrative synthesis of its hallmarks for palliative care clinicians.

Chronic obstructive pulmonary disease (COPD) is a life-limiting condition and the third leading cause of death worldwide. People with COPD experience physical and psychological symptoms and functional limitations that impair their quality of life. Their caregivers face adverse clinical outcomes due to personal, social, and financial demands.

Hydroxychloroquine prevents resistance and potentiates the antitumor effect of SHP2 inhibition in NF1-associated malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas and the primary cause of mortality in patients with neurofibromatosis type 1 (NF1). These malignancies develop within preexisting benign lesions called plexiform neurofibromas (PNs). PNs are solely driven by biallelic loss eliciting RAS pathway activation, and they respond favorably to MEK inhibitor therapy.

IL-21 shapes the B cell response in a context-dependent manner.

The T-cell-derived cytokine IL-21 is crucial for germinal center (GC) responses, but its precise role in B cell function has remained elusive. Using IL-21 receptor (Il21r) conditional knockout mice and ex vivo culture systems, we demonstrate that IL-21 has dual effects on B cells. While IL-21 induced apoptosis in a STAT3-dependent manner in naive B cells, it promoted the robust proliferation of pre-activated B cells, particularly IgG1 B cells.

A Social Network Lens to Community Health Worker Influence and Impact.

Community Health Workers (CHWs) are members of healthcare teams that are integrated in, and often share language, beliefs, and lived experiences with their communities. They use their formal and informal social networks to promote healthy behavior, to connect community members to resources, and to build more resilient community networks. We propose a framework to conceptualize CHW interventions aiming to operationalize and optimize CHW social relations and networks.

Benign Soft Tissue Lesions Responsible for Pain: When and How Should the IR Intervene.

In most of the cases Interventional Radiology techniques and therapies are proposed for the management of symptomatic soft tissue benign tumors responsible for pain and/or compression symptoms aiming to offer a curative intent by means of tumor necrosis with subsequent symptoms' management and improvement of life quality. The ablative therapies include chemical, thermal and non-thermal approaches while, trans-arterial (chemo)embolization also has a distinct role. Adjunct ancillary techniques should be performed whenever necessary to increase efficacy and safety and avoid or reduce complications.