Molecular Profiling Identifies CD49d and CD79b as Predictive Markers for Acquired Acalabrutinib Resistance in Patients With Chronic Lymphocytic Leukemia.

Contemporary studies of Bruton tyrosine kinase inhibitor (BTKi) resistance focus on mutations in the B-cell receptor (BCR) pathway, but alternative mechanisms of resistance remain undefined. Here, we sought to identify novel predictive markers of acquired resistance to acalabrutinib, a second-generation BTKi, in patients with chronic lymphocytic leukemia (CLL). Clinical samples from 41 patients with relapsed/refractory or treatment-naive CLL receiving acalabrutinib as part of a clinical trial (NCT02029443) were divided into two groups: those who continued to respond to treatment (NP, n = 23) and those who developed progressive disease on acalabrutinib therapy (PD, n = 18).

Cytoreductive Nephrectomy Following Immunotherapy: Evolution, Pearls, and Pitfalls of Treatment.

Introduction: Renal Cell Carcinoma (RCC) is among the most frequently diagnosed malignancies in both genders with over 81,000 estimated cases in 2024. Despite increasing incidence of renal cell carcinomas <4 cm, up to 1/3 of patients diagnosed with RCC exhibit metastatic disease (mRCC) at time of diagnosis. Cytoreductive nephrectomy (CN), a procedure which encompasses the surgical removal of the primary tumor in patients with metastatic disease, was offered upfront as standard of care during the cytokine era; however, as systemic treatment has evolved, the role of CN in mRCC patients has become less clear.

Features of disposable e-cigarettes and their association with pricing and consumer preference: Evidence from web data of US online stores.

Background And Aims: Disposable e-cigarettes designed for one-time use are the most popular option among youth users in the United States (US). Product-level data (e.g.

Inhibiting de novo lipogenesis identifies a therapeutic vulnerability in therapy-resistant colorectal cancer.

A significant clinical challenge in patients with colorectal cancer (CRC), which adversely impacts patient survival, is the development of therapy resistance leading to a relapse. Therapy resistance and relapse in CRC is associated with the formation of lipid droplets (LD) by stimulating de novo lipogenesis (DNL). However, the molecular mechanisms underlying the increase in DNL and the susceptibility to DNL-targeted therapies remain unclear.

The Fifth Annual Symposium of the Midwest Aging Consortium.

As the healthcare burden caused by an increasingly aging population rapidly rises, a pressing need exists for innovative geroscience research that can elucidate aging mechanisms and precipitate the development of therapeutic interventions to support healthy aging. The Fifth Annual Midwest Aging Consortium Aging Research symposium, held from April 28-30, 2024, was hosted by The Ohio State University in Columbus, Ohio and featured presentations from investigators across the Midwestern United States. This report summarizes the research presented at the symposium, whose topics included cellular senescence and the aging brain, metabolism and metabolic interventions, nutrition, redox mechanisms and biomarkers, and stress mechanisms.

Olutasidenib demonstrates significant clinical activity in mutated IDH1 acute myeloid leukaemia arising from a prior myeloproliferative neoplasm.

Acute myeloid leukaemia (AML) arising from a myeloproliferative neoplasm (MPN) is more aggressive and less responsive to therapies compared to de novo AML. Olutasidenib, an oral small-molecule inhibitor of mutated IDH1 (mIDH1), showed encouraging and durable responses in a phase 1/2 study of adults with post-MPN mIDH1 AML. Patients received olutasidenib 150 mg BID monotherapy or in combination with azacitidine.

Dynamic human gut microbiome and immune shifts during an immersive psychosocial intervention program.

Background: Although depression is a leading cause of disability worldwide, the pathophysiological mechanisms underlying this disorder-particularly those involving the gut microbiome-are poorly understood.

Method: To investigate, we conducted a community-based observational study to explore complex associations between changes in the gut microbiome, cytokine levels, and depression symptoms in 52 participants (M = 49.56, SD = 13.

Long-Term Follow-Up and Overall Survival in NRG258, a Randomized Phase III Trial of Chemoradiation Versus Chemotherapy for Locally Advanced Endometrial Carcinoma.

This randomized phase III trial aimed to determine whether treatment with cisplatin and volume-directed radiation followed by carboplatin and paclitaxel for four cycles (chemoradiotherapy [C-RT]) increased recurrence-free survival (RFS) and overall survival (OS) when compared with carboplatin and paclitaxel for six cycles (chemotherapy [CT]) in locally advanced endometrial cancer (UC). Previously reported results showed that C-RT did not improve RFS compared with CT. Here we report the final OS analysis.

Integrating artificial intelligence in renal cell carcinoma: evaluating ChatGPT's performance in educating patients and trainees.

Background: OpenAI's ChatGPT is a large language model-based artificial intelligence (AI) chatbot that can be used to answer unique, user-generated questions without direct training on specific content. Large language models have significant potential in urologic education. We reviewed the primary data surrounding the use of large language models in urology.

Perioperative systemic therapy in high-risk renal cell carcinoma following nephrectomy: a narrative review.

Background And Objective: For patients with resectable renal cell carcinoma (RCC), extirpative surgery with curative intent remains the standard of care. Despite surgical resection, most patients with high-risk features experience disease recurrence. The role of perioperative systemic therapy in the management of these patients' disease remains unclear.

Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric, Version 3.2024, NCCN Clinical Practice Guidelines In Oncology.

Multigene panel testing has allowed for the detection of a growing number of inherited pathogenic/likely pathogenic variants in people at high risk of cancer, including endometrial cancer (EC). Hereditary syndromes associated with EC include Lynch syndrome, PTEN hamartoma tumor syndrome, and Peutz-Jeghers syndrome. This manuscript provides the latest recommendations from the NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric on the screening and management of EC in patients at high risk for these syndromes, as well as the advantages and limitations of multigene panel testing.

NCCN Guidelines® Insights: Survivorship, Version 2.2024.

The NCCN Guidelines for Survivorship include recommendations for screening, evaluation, and treatment of psychosocial and physical problems resulting from adult-onset cancer and its treatment. They also include recommendations to promote healthy behaviors and immunizations in survivors and provide a framework for care coordination. These NCCN Guidelines Insights summarize the panel's current recommendations regarding sexual health and fertility.

Molecular Pathway and Immune Profile Analysis of IPMN-Derived Versus PanIN-Derived Pancreatic Ductal Adenocarcinomas.

Intraductal papillary mucinous neoplasms (IPMN) are commonly detected pancreatic cysts that may transform into pancreatic ductal adenocarcinoma (PDAC). Predicting which IPMNs will progress to PDAC remains a clinical challenge. Moreover, identifying those clinically evident IPMNs for which a surveillance approach is best is a dire clinical need.

Associations of frailty with survival, hospitalization, functional decline, and toxicity among older adults with advanced non-small cell lung cancer.

Introduction: Among older adults with cancer receiving chemotherapy, frailty indices predict OS and toxicity. Given the increased use of immunotherapy and targeted therapy for advanced non-small cell lung cancer (aNSCLC), we evaluated frailty and Karnofsky Performance Status (KPS) among older adults with aNSCLC receiving chemotherapy, immunotherapy, and/or targeted therapy.

Methods: Patients aged ≥ 65 with aNSCLC starting systemic therapy with non-curative intent underwent geriatric assessments over 6 months.

A blueprint for pursuing therapeutic interventions and early phase clinical trials in clonal haematopoiesis.

The age-associated mutational state of clonal haematopoiesis (CH) is linked to multiple adverse health outcomes. As higher risk CH can lead to progressive neoplastic or vascular disease, there is interest in developing clinical trials to mitigate risk associated with CH. Given the high prevalence of CH, data from clinical trials could have broad public health implications for screening and therapy.

Efficacy and Safety of Venetoclax Plus Azacitidine for Patients With Treatment-Naive High-Risk Myelodysplastic Syndromes.

Patients with higher-risk myelodysplastic syndromes (HR MDS) have a median survival of ~1.5 years with azacitidine, and hematopoietic stem cell transplantation is their only curative option. Therefore, improved therapies are needed.

Weekly Cisplatin Cycles and Outcomes for Chemoradiation in Head and Neck Cancer.

Importance: National Comprehensive Cancer Network guidelines recommend weekly cisplatin as an alternative concurrent systemic therapy for definitive chemoradiation in patients with head and neck cancer. However, the impact of different levels of adherence to weekly cisplatin on outcomes stratified by human papillomavirus p16 status remains unclear.

Objective: To evaluate the association between the number of weekly cisplatin cycles and outcomes.

Phase II study of MEK inhibitor trametinib alone and in combination with AKT inhibitor GSK2141795/uprosertib in patients with metastatic triple negative breast cancer.

Purpose: While MEK inhibitors demonstrated activity in metastatic triple negative breast cancer (mTNBC) preclinical studies, preclinical, and clinical studies implicate rapid development of resistance limiting clinical benefit. The purpose of this study was to determine response rate for Trametinib alone and in combination with Uprosertib in patients with mTNBC previously treated with chemotherapy.

Methods: This was an open-label, two-part, phase II, single-arm, multicenter study.

Analysis of a Pilot Study Delivering Cancer Survivorship Education to Community Healthcare Professionals Utilizing the Project ECHO Model.

As the number and needs of cancer survivors grow, innovative ways to enhance survivorship expertise are needed. This pilot study evaluated a 12-week cancer survivorship curriculum delivered to two cohorts of providers at affiliated sites within the Mercy Health System, utilising the Project ECHO® model, on provider self-efficacy (SE), knowledge (KN), and professional improvement (PI). Providers received six 1-hour sessions, informed by provider needs assessment, over 12 weeks.

Impact of immunological aging on T cell-mediated therapies in older adults with multiple myeloma and lymphoma.

The treatment landscape for lymphoma and multiple myeloma, which disproportionally affect older adults, has been transformed by the advent of T cell-mediated immunotherapies, including immune checkpoint inhibition, T cell-engaging bispecific antibodies, and chimeric antigen receptor (CAR) T cell therapy, during the last decade. These treatment modalities re-enable the patient's own immune system to combat malignant cells and offer the potential for sustained remissions and cure for various diseases.Age profoundly affects the physiological function of the immune system.

Primary Intraosseous Solitary Fibrous Tumor of the Mandible: Report of a Diagnostically Challenging Case with NAB2::STAT6 Fusion and Review of the Literature.

Introduction: Solitary fibrous tumor (SFT) represents an uncommon mesenchymal neoplasm affecting primarily the extremities and deep soft tissues with, overall, benign but locally aggressive biologic behavior and an underlying pathognomonic NAB2::STAT6 fusion. Intraosseous SFTs are infrequent, and involvement of the jawbones is exceedingly rare.

Case Presentation: A 54-year-old woman presented with an asymptomatic, well-demarcated, multilocular radiolucency of the left posterior mandible featuring focally irregular borders, root resorption and lingual cortex perforation.

Impact of Preoperative Systemic Therapy on Cytoreductive Nephrectomy Outcomes in the National Surgical Quality Improvement Program (NSQIP).

Introduction: Management of metastatic renal cell carcinoma (mRCC) is highly individualized and often involves cytoreductive nephrectomy (CN) and systemic therapy (ST). The optimal sequencing of CN and ST is uncertain. A difference in perioperative outcomes based on sequence of CN and ST could influence decisionmaking.

'Authentic' or 'corny': LGBTQ+ young adults respond to visual, thematic and semantic elements of culturally targeted tobacco public education advertisements.

Background: Lesbian, gay, bisexual, transgender and queer (LGBTQ+) young adults (YA) experience disparities in nicotine and tobacco use. Mass-reach health communications can prevent nicotine and tobacco initiation and progression, but LGBTQ+adults report low engagement. Although cultural targeting (CT) could reach LGBTQ+YA, we know little about the strategies that resonate with this population.

Monocyte-derived extracellular vesicles, stimulated by Trypanosoma cruzi, enhance cellular invasion in vitro via activated TGF-β1.

During cell invasion, large Extracellular Vesicle (lEV) release from host cells was dose-dependently triggered by Trypanosoma cruzi metacyclic trypomastigotes (Mtr). This lEV release was inhibited when IP-mediated Ca exit from the ER and further Ca entry from plasma membrane channels was blocked, but whilst any store-independent Ca entry (SICE) could continue unabated. That lEV release was equally inhibited if all entry from external sources was blocked by chelation of external Ca points to the major contributor to Mtr-triggered host cell lEV release being IP/store-mediated Ca release, SICE playing a minor role.