hematology Oncology emergencies

PURPOSE OF REVIEW: Our review delves into the progress across urological malignancies and discusses ongoing challenges and future directions in antibody-drug conjugate (ADC) development, emphasising their transformative potential in cancer care. RECENT FINDINGS: ADCs have advanced from hematologic to solid tumours, notably in breast cancer, and are now pivotal in metastatic urological cancers as both monotherapies and in combination regimens, underscored by the FDA's approval of enfortumab vedotin and sacituzumab govitecan for metastatic urothelial cancer...

To external validate the risk assessment model (RAM) of venous thromboembolism (VTE) in multicenter internal medicine inpatients. We prospectively collected 595 internal medical patients (310 with VTE patients, 285 non-VTE patients) were from Beijing Shijitan Hospital, Beijing Chaoyang Hospital, and the respiratory department of Beijing Tsinghua Changgeng Hospital from January 2022 to December 2022 for multicenter external validation. The prediction ability of Caprini RAM, Padua RAM, The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) RAM, and Shijitan (SJT) RAM were compared...

In Germany, physicians qualify for emergency medicine by combining a specialty medical training-e.g. internal medicine-with advanced training in emergency medicine according to the statutes of the State Chambers of Physicians largely based upon the Guideline Regulations on Specialty Training of the German Medical Association. Internal medicine and their associated subspecialities represent an important column of emergency medicine. For the internal medicine aspects of emergency medicine, this curriculum presents an overview of knowledge, skills (competence levels I-III) as well as behaviours and attitudes allowing for the best treatment of patients...

Ferroptosis is an unconventional programmed cell death mode caused by phospholipid peroxidation dependent on iron. Emerging immunotherapies (especially immune checkpoint inhibitors) have the potential to enhance lung cancer patients' long-term survival. Although immunotherapy has yielded significant positive applications in some patients, there are still many mechanisms that can cause lung cancer cells to evade immunity, thus leading to the failure of targeted therapies. Immune-tolerant cancer cells are insensitive to conventional death pathways such as apoptosis and necrosis, whereas mesenchymal and metastasis-prone cancer cells are particularly vulnerable to ferroptosis, which plays a vital role in mediating immune tolerance resistance by tumors and immune cells...

In the tumor microenvironment (TME), myeloid cells play a pivotal role. Myeloid-derived immunosuppressive cells, including tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), are central components in shaping the immunosuppressive milieu of the tumor. Within the TME, a majority of TAMs assume an M2 phenotype, characterized by their pro-tumoral activity. These cells promote tumor cell growth, angiogenesis, invasion, and migration. In contrast, M1 macrophages, under appropriate activation conditions, exhibit cytotoxic capabilities against cancer cells...

Although immune checkpoint inhibitors have revolutionized the treatment of several advanced solid cancers, in colorectal cancer, the transformative benefit of these innovative medicines is currently limited to those with deficient mismatch repair or high microsatellite instability. Tumor mutational burden (TMB) has emerged as a potential predictor of immunotherapy benefit, but the lack of standardization in its assessment and reporting has hindered the introduction of this biomarker in routine clinical practice...

Pediatric neoplasms represent a complex group of malignancies that pose unique challenges in terms of diagnosis, treatment, and understanding of the underlying molecular pathogenetic mechanisms. Erythropoietin-producing hepatocellular receptors (EPHs), the largest family of receptor tyrosine kinases and their membrane-tethered ligands, ephrins, orchestrate short-distance cell-cell signaling and are intricately involved in cell-pattern morphogenesis and various developmental processes. Unraveling the role of the EPH/ephrin signaling pathway in the pathophysiology of pediatric neoplasms and its clinical implications can contribute to deciphering the intricate landscape of these malignancies...

Cervical cancer (CaCx) ranks as the fourth most prevalent cancer among women globally. Persistent infection of high-risk human papillomaviruses (HR-HPVs) is major etiological factor associated with CaCx. Signal Transducer and Activator of Transcription 3 (STAT3), a prominent member of the STAT family, has emerged as independent oncogenic driver. It is a target of many oncogenic viruses including HPV. How STAT3 influences HPV viral gene expression or gets affected by HPV is an area of active investigation. A better understanding of host-virus interaction will provide a prognostic and therapeutic window for CaCx control and management...

PURPOSE: Recognizing unmet care needs among cancer patients is crucial for improving a person-centered and tailored approach to survivorship care. This study aimed to explore the prevalence of unmet supportive care needs, pinpointing entity-specific areas of burden, and to identify factors associated with unmet needs within a diverse sample of cancer patients. METHODS: In this cross-sectional sub-study of a large multicenter study, 944 adult cancer patients reported supportive care needs via the well-validated SCNS...

INTRODUCTION: Chimeric antigen receptor (CAR) T cells have revolutionized treatment of multiple hematologic malignancies. Engineered cellular therapies now offer similar hope to transform management of solid tumors and autoimmune disease. However, toxicities can be serious and often require hospitalization. AREAS COVERED: We review the two chief toxicities of CAR T therapy, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and the rarer immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome...

Immune checkpoints inhibitors (ICIs) have markedly improved the therapeutic management of advanced NSCLC and, more recently, they have demonstrated efficacy also in the early-stage disease. Despite better survival outcomes with ICIs compared to standard chemotherapy, a large proportion of patients can derive limited clinical benefit from these agents. So far, few predictive biomarkers, including the programmed death-ligand 1 (PD-L1), have been introduced in clinical practice. Therefore, there is an urgent need to identify novel biomarkers to select patients for immunotherapy, to improve efficacy and avoid unnecessary toxicity...

Chimeric antigen receptor (CAR) T adoptive cell therapy has transformed the treatment of human hematologic malignancies. However, its application for the treatment of solid tumors remains challenging. An exciting avenue for advancing this field lies in the use of pet dogs, in which cancers that recapitulate the biology, immunological features, and clinical course of human malignancies arise spontaneously. Moreover, their large size, outbred genetic background, shared environment with humans, and immunocompetency make dogs ideal for investigating and optimizing CAR therapies before human trials...

Hematopoiesis is a tightly regulated process that produces all adult blood cells and immune cells from multipotent hematopoietic stem cells (HSCs). HSCs usually remain quiescent, and in the presence of external stimuli like infection or inflammation, they undergo division and differentiation as a compensatory mechanism. Normal hematopoiesis is impacted by systemic inflammation, which causes HSCs to transition from quiescence to emergency myelopoiesis. At the molecular level, inflammatory cytokine signaling molecules such as tumor necrosis factor (TNF), interferons, interleukins, and toll-like receptors can all cause HSCs to multiply directly...

Adoptive immunotherapy in the T cell landscape exhibits efficacy in cancer treatment. Over the past few decades, genetically modified T cells, particularly chimeric antigen receptor T cells, have enabled remarkable strides in the treatment of hematological malignancies. Besides, extensive exploration of multiple antigens for the treatment of solid tumors has led to clinical interest in the potential of T cells expressing the engineered T cell receptor (TCR). TCR-T cells possess the capacity to recognize intracellular antigen families and maintain the intrinsic properties of TCRs in terms of affinity to target epitopes and signal transduction...

Cancer immunotherapy and vaccine development have significantly improved the fight against cancers. Despite these advancements, challenges remain, particularly in the clinical delivery of immunomodulatory compounds. The tumor microenvironment (TME), comprising macrophages, fibroblasts, and immune cells, plays a crucial role in immune response modulation. Nanoparticles, engineered to reshape the TME, have shown promising results in enhancing immunotherapy by facilitating targeted delivery and immune modulation...

Multiple myeloma (MM) is a hematologic malignancy notorious for its high relapse rate and development of drug resistance, in which cell adhesion-mediated drug resistance plays a critical role. This study integrated four RNA sequencing datasets (CoMMpass, GSE136337, GSE9782, and GSE2658) and focused on analyzing 1706 adhesion-related genes. Rigorous univariate Cox regression analysis identified 18 key prognosis-related genes, including KIF14, TROAP, FLNA, MSN, LGALS1, PECAM1, and ALCAM, which demonstrated the strongest associations with poor overall survival (OS) in MM patients...

BACKGROUND: Invasive fungal disease (IFD) is typically aggressive and related with high mortality in children with a hematological malignancy. The association of medical and surgical treatment may ameliorate the outcome. The aim of this study was to analyze the surgical treatment of fungal infections in pediatric oncological populations. METHODS: Retrospective study (2000-2022) of a single-center experience. We reviewed the medical record of all patients with hematologic malignancies and IFD, analyzing the outcome...

Adults and children with sickle cell disease (SCD) are predominantly African American, with pain-related health disparities. We examined opioid prescription fill patterns in adults and children with SCD and compared factors associated with fills in North Carolina Medicaid enrollees. Our retrospective cohort study included 955 enrollees diagnosed with SCD having at least one opioid fill. Associations were measured between two cohorts (12 and 24 mo of continuous enrollment) for the following characteristics: sex, age, enrollee residence, hydroxyurea adherence, comanagement, enrollment in Community Care North Carolina, prescription for short versus short and long-acting opioids, and emergency department reliance...

Background: Pediatric oncology patients receive multiple modalities of therapy to treat their malignancies. These modalities have the potential for acute toxicity and late effects. In the last decade, a new modality known as targeted biological therapy, has become an integral part of treatment for pediatric cancers. As targeted therapy use has increased, adverse events specific to these targeted agents have emerged, requiring a new effort focused on providing education to patients and families regarding how best to report, monitor, and manage these adverse events...

BACKGROUND: Patients with acute myeloid leukaemia have high rates of relapse, especially if they are unable to complete standard consolidation strategies or allogeneic haematopoietic stem-cell transplantation (HSCT). The phase 3 QUAZAR AML-001 study showed an overall survival benefit with oral azacitidine maintenance. The BCL2 inhibitor venetoclax is highly active in acute myeloid leukaemia and synergistic with azacitidine. We aimed to evaluate the efficacy and safety of low dose azacitidine plus venetoclax as maintenance therapy in acute myeloid leukaemia...