Elucidating PTEN conformational dynamics and phosphatase regulation via integrative modeling and mutation prediction.

PTEN (Phosphatase and TENsin homolog deleted on chromosome ten) is a major tumor suppressor gene that is frequently mutated or lost under cancerous conditions. PTEN is a dual-specificity phosphatase that negatively regulates the PI3K/AKT/mTOR signaling pathway at the plasma membrane (PM). Its functional regulation and cellular localization are known to be conformationally driven.

AA amyloidosis with multiorgan involvement secondary to familial Mediterranean fever (FMF): dreadful consequences of delayed diagnosis and management.

Familial Mediterranean fever (FMF) is an autoinflammatory disorder that can lead to progressive AA amyloidosis if not diagnosed and treated promptly. We present a case of a middle-aged male with extensive multiorgan involvement due to AA amyloidosis secondary to FMF. His medical journey spans over a decade, with disease progression affecting the kidneys, bone marrow, liver, heart, lungs and gastrointestinal tract.

Multipotent lineage potential in B cell acute lymphoblastic leukemia is associated with distinct cellular origins and clinical features.

Developmental origins and their associations with lineage plasticity and treatment response in B-cell progenitor acute lymphoblastic leukemia (B-ALL) are mostly unexplored. Here, we integrated single-cell transcriptome sequencing (scRNA-seq) of 89 B-ALL samples with a single-cell atlas of normal human B cell development incorporating functional and molecular assays. We observed subtype- and sample-dependent correlation with normal developmental stage, with intra-subtype and intra-patient heterogeneity.

Plasmablastic Lymphoma-A Crosstalk Between Myeloma and Lymphoma.

Plasmablastic lymphoma (PBL) is a rare type of large B-cell lymphoma that primarily affects immunocompromised individuals, often associated with viral infections such as Human Immunodeficiency Virus (HIV) and Epstein-Barr Virus (EBV). The diagnosis of PBL is often difficult to ascertain due to its overlapping clinical and pathological features with multiple myeloma and large B cell lymphoma. The primary organs of involvement are typically the gastrointestinal system, lymph nodes, oral mucosa, with some involvement of the skin.

Transcriptomic Profiling of Relapsed Rhabdomyosarcoma: Pre- and Post-Treatment Tissue Analysis Reveals Molecular Characteristics of Treatment Failure.

Background: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. Historically classified based on histology, advances in molecular profiling have allowed further sub-classification, which has improved risk stratification. Although molecular profiling has improved our understanding of disease progression and risk, the molecular evolution of therapy resistance in RMS remains poorly characterized.

Outcomes of teclistamab in patients with relapsed/refractory multiple myeloma with prior exposure to BCMA-directed therapy: a multicenter study from the U.S. Multiple Myeloma Immunotherapy Consortium.

Data describing outcomes of teclistamab in multiple myeloma patients with prior exposure to BCMA-directed therapy (BCMA-DT) are limited. The goal of this multicenter retrospective analysis was to report the efficacy and safety of standard-of-care teclistamab in patients with prior BCMA-DT. A total of 385 patients were included, of whom 193 (50%) had received prior BCMA-DT, including 47 (24%) patients with prior antibody-drug conjugate (ADC)-only, 99 (51%) with chimeric antigen receptor T-cell therapy (CAR T)-only, 36 (19%) with both ADC and CAR T, 6 (3%) with bispecific antibody-only, and 5 (3%) with other combinations.

Infections in VEXAS syndrome: a systematic review of the literature.

Vacuolation, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a multisystem disease for which chronic immunosuppression is needed. Opportunistic infections are common; however, a clear prophylaxis regimen is not defined. A systematic review of the literature was undertaken.

Up-front alternative donor HCT in severe aplastic anemia: gaps and opportunities to translate evidence into practice.

Severe aplastic anemia (SAA) is a rare and life-threatening bone marrow failure disorder. Immunosuppressive therapy (IST) with antithymocyte globulin and cyclosporine has long been a frontline treatment option in SAA; however, its limited durability and risk of long-term complications such as secondary malignancies remain a drawback in this treatment modality. Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative option with significantly improved outcomes over the long term, particularly with HLA-matched related donors.

Association between Exposure to Statin Choice and Adherence to Statins: An Observational Cohort Study.

BackgroundStatin Choice is a shared decision-making encounter tool embedded in the electronic health record.ObjectiveTo describe the association between the use of Statin Choice, statin prescriptions by clinicians, prescription fills (primary adherence), and statin adherence at 12 mo (secondary adherence).DesignObservational cohort study at the Cleveland Clinic Health System.

Risk Factors for Solid Organ Graft Failure and Death in Hematopoietic Cell Transplant Recipients Undergoing Solid Organ Transplantation: A Retrospective Center for International Blood and Marrow Transplant Research and Organ Procurement and Transplantation Network Study.

Background: There is a growing population of hematopoietic cell transplantation (HCT) survivors who later require a solid organ transplant (SOT). However, there are limited data on survival, risk factors (RFs) for SOT graft loss, and death.

Methods: This is a retrospective Center for International Blood and Marrow Transplant Research study that included recipients of HCT followed by SOT between 2001 and 2017.

Risk Factors for Solid Organ Graft Failure and Death in Solid Organ Transplant Recipients Undergoing Hematopoietic Cell Transplantation: A Retrospective Center for International Blood and Marrow Transplant Research (CIBMTR) and Organ Procurement and Transplantation Network (OPTN) Study.

Background: There is a growing population of solid organ transplant (SOT) survivors who subsequently require a hematopoietic cell transplant (HCT), although there are limited data on survival, risk factors for SOT graft loss, and death in this cohort.

Methods: This retrospective Center for International Blood and Marrow Transplant Research study included recipients of SOT followed by HCT between 1989 and 2017. HCT data were merged with organ transplant data from the Organ Procurement and Transplantation Network.

Disparities in Access to Multigene Testing in Early-Stage, HR-positive, HER2-negative, Lymph Node-negative Breast Cancer.

Background: Multigene testing (MGT) has refined breast cancer treatment. We examined real-world access to MGT for early-stage (I-II), HR-positive, HER2-negative, node-negative breast cancer and identified factors related to disparities.

Materials And Methods: This retrospective analysis used the National Cancer Database (2007-2017).

Intra-arterial chemotherapy for retinoblastoma: a performance analysis.

Aim: To conduct a performance analysis of intra-arterial chemotherapy (IAC).

Material And Methods: Comprehensive data search in MEDLINE from inception until December 2023. Peer-reviewed, English-language, clinical studies (retrospective, prospective, trials, non-randomised) and case series.

State-wise disparities and temporal trends in acute myeloid leukemia (AML) in the United States of America (USA).

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. We utilized Global Burden of Diseases 2021 data to assess age-standardized incidence rates (ASIR), age-standardized death rates (ASDR) per 100,000 population, and annual percentage changes (APC) of ASIR and ASDR of AML across USA states. Statistical modeling, including 2 two-sample t-test, was done.

Signalling Network Analysis of Blood Mononuclear Cells From Clinical Samples by Bivariate Correlation.

Signalling networks have been assessed in blood cells by assessing individual phosphoantigens. We considered the possibility that bivariate correlations involving a series of signalling molecules could be used to delineate functional signalling networks in cells from clinical samples. Here, we describe a novel approach to signalling network analysis using enhanced flow cytometry to provide increased resolving power and restricted-dimensional cytometry which simplifies the analysis so that the precision of the analysis is optimised.

Artificial Intelligence-Based Digital Histologic Classifier for Prostate Cancer Risk Stratification: Independent Blinded Validation in Patients Treated With Radical Prostatectomy.

Purpose: Artificial intelligence (AI) tools that identify pathologic features from digitized whole-slide images (WSIs) of prostate cancer (CaP) generate data to predict outcomes. The objective of this study was to evaluate the clinical validity of an AI-enabled prognostic test, PATHOMIQ_PRAD, using a clinical cohort from the Cleveland Clinic.

Methods: We conducted a retrospective analysis of PATHOMIQ_PRAD using CaP WSIs from patients who underwent radical prostatectomy (RP) between 2009 and 2022 and did not receive adjuvant therapy.

A phase 2 study of itacitinib alone or in combination with low-dose ruxolitinib in patients with myelofibrosis.

Background: The Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib has demonstrated efficacy/safety in patients with myelofibrosis; however, not all patients experience optimal and/or stable response, in part owing to dose-limiting toxicities. This phase 2 study evaluated itacitinib (JAK1-selective inhibitor) efficacy/safety alone or combined with low-dose ruxolitinib.

Methods: Cohort A received itacitinib 200 mg once daily (QD) plus ruxolitinib at a previous stable dose (≤15 mg total daily dose).

First-in-human phase I/II, open-label study of mRNA-2416 alone or combined with durvalumab in patients with advanced solid tumors and ovarian cancer.

Background: mRNA-2416 is a novel lipid nanoparticle-encapsulated messenger RNA (mRNA) encoding human OX40 ligand (OX40L) for intratumoral (Itu) injection. OX40L plus immune checkpoint inhibitor (ICI) increased preclinical antitumor activity, thus mRNA-2416 plus ICI may potentiate antitumor activity.

Methods: This first-in-human, phase I/II, open-label, multicenter study examined the safety, tolerability, and efficacy of mRNA-2416 alone (arm A) or with durvalumab (arm B) in patients with advanced solid tumors or lymphoma (NCT03323398).

Standard Dose Versus Reduced Dose Single Fraction Preoperative Radiosurgery for Resected Brain Metastases (PROPS-BM) International Multicenter Cohort Study.

Purpose: Single fraction preoperative stereotactic radiosurgery (SRS) has historically used a 10% to 20% dose reduction standard dosing. However, the effects of this dose reduction are not well characterized. The goal of this study was to compare outcomes and toxicity of standard dose (SD) with reduced dose (RD) single fraction preoperative SRS.

Comparing Outcomes of First-Line Intensive Chemotherapeutic Regimens in Adult Patients With Acute Lymphoblastic Leukemia at a Tertiary Center.

Background: Survival outcomes of acute lymphoblastic leukemia (ALL) in adults remain inferior to those in the pediatric population. Limited data is present directly comparing different first-line intensive regimens in adult patients with ALL.

Methods: We conducted a retrospective study comparing outcomes of first-line intensive chemotherapeutic regimens utilized in adult ALL patients at Cleveland Clinic.

Thymomas and Thymic Carcinomas, Version 2.2025, NCCN Clinical Practice Guidelines In Oncology.

Thymomas and thymic carcinomas are rare mediastinal tumors that originate in the thymus. Patients with thymoma may experience symptoms associated with autoimmune paraneoplastic diseases (such as myasthenia gravis), which typically do not occur in patients with thymic carcinoma. The NCCN Guidelines for Thymomas and Thymic Carcinomas provide guidance for the diagnosis, treatment, and surveillance of patients with thymoma and thymic carcinoma.