Targeting Protein Kinase C-α Prolongs Survival and Restores Liver Function in Sepsis: Evidence from Preclinical Models.

Sepsis is a life-threatening organ failure resulting from a poorly regulated infection response. Organ dysfunction includes hepatic involvement, weakening the immune system due to excretory liver failure, and metabolic dysfunction, increasing the death risk. Although experimental studies correlated excretory liver functionality with immune performance and survival rates in sepsis, the proteins and pathways involved remain unclear.

The Safety and Late Hemodynamics of Donor Cardiac Undersizing in Heart Transplantation.

Background: Predicted heart mass ratio (PHMr) has become the standard donor-recipient size matching method in heart transplantation. While utilization of small PHMr hearts is associated with increased one-year mortality, the underlying mechanisms and time horizon of mortality remain uncertain.

Methods: A single institution analysis of isolated heart transplant recipients (01/2019-7/2022) was performed (N=334).

Out of the ice age: Preservation of cardiac allografts with a reusable 10 °C cooler.

Objective: Static cold storage with ice has been the mainstay of cardiac donor preservation. Early preclinical data suggest that allograft preservation at 10 °C may be beneficial. We tested this hypothesis by using a static 10 °C storage device to preserve and transport cardiac allografts.

Standardizing Nutritional Care for Cancer Patients: Implementation and Evaluation of a Malnutrition Risk Screening.

Introduction: Cancer-related malnutrition is a highly prevalent, yet often overlooked concern in clinical practice. Although cancer-related management guidelines recommend standardized nutritional care, its implementation is scarce. The aim of this study was to investigate the prevalence of malnutrition and the medical need for nutrition counseling in cancer patients employing a novel standardized nutritional management program (containing malnutrition risk screening, nutritional assessment, and counseling).

Impact of TP53 Mutation Status in Elderly AML Patients When Adding All-Trans Retinoic Acid or Valproic Acid to Decitabine.

In a randomized phase II trial (AMLSG 14-09, NCT00867672) of elderly, newly diagnosed AML patients, ATRA combined with decitabine (DEC) significantly improved the overall response rate (ORR) and survival also in patients with adverse-risk genetics, without adding toxicity. We performed a post hoc analysis to determine the predictive impact of TP53 status. Despite a nominally higher ORR, the clinically meaningful survival benefit when adding ATRA to DEC was diminished, but not completely negated, in TP53-mutated patients.

Single or Double Induction With 7 + 3 Containing Standard or High-Dose Daunorubicin for Newly Diagnosed AML: The Randomized DaunoDouble Trial by the Study Alliance Leukemia.

Purpose: To determine the optimal daunorubicin dose and number of 7 + 3 induction cycles in newly diagnosed AML, this randomized controlled trial compared a once daily dose of 60 mg/m with 90 mg/m daunorubicin in the first 7 + 3 induction and one versus two cycles of 7 + 3 induction.

Patients And Methods: Patients age 18-65 years with newly diagnosed AML were randomly assigned to 60 versus 90 mg/m daunorubicin once daily plus cytarabine. Patients with marrow blasts below 5% on day 15 after first induction were randomly assigned to receive a second induction cycle or no second induction cycle.

Assessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma (HD21): a randomised, multicentre, parallel, open-label, phase 3 trial.

Background: Intensified systemic chemotherapy has the highest primary cure rate for advanced-stage, classical Hodgkin lymphoma but this comes with a cost of severe and potentially life long, persisting toxicities. With the new regimen of brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD), we aimed to improve the risk-to-benefit ratio of treatment of advanced-stage, classical Hodgkin lymphoma guided by PET after two cycles.

Methods: This randomised, multicentre, parallel, open-label, phase 3 trial was done in 233 trial sites across nine countries.

Effective bridging strategies prior to infusion with tisagenlecleucel results in high response rates and long-term remission in relapsed/refractory large B-cell lymphoma: findings from a German monocentric study.

Background: Incorporating chimeric antigen receptor (CAR)-T cell therapy into relapsed or refractory large B-cell lymphoma (rr LBCL) treatment algorithms has yielded remarkable response rates and durable remissions, yet a substantial portion of patients experience progression or relapse. Variations in outcomes across treatment centers may be attributed to different bridging strategies and remission statuses preceding CAR-T cell therapy.

Patients: Twenty-nine consecutive adult patients receiving tisagenlecleucel (tisa-cel) for rr LBCL from December 2019 to February 2023 at Jena University Hospital were analyzed.

Synergistic Effects of the RAR Agonist Tamibarotene and the Menin Inhibitor Revumenib in Acute Myeloid Leukemia Cells with KMT2A Rearrangement or NPM1 Mutation.

Inhibition of menin in acute myeloid leukemia (AML) harboring histone-lysine--methyltransferase 2A rearrangement (KMT2Ar) or the mutated Nucleophosmin gene (NPM1c) is considered a novel and effective treatment approach in these patients. However, rapid acquisition of resistance mutations can impair treatment success. In patients with elevated retinoic acid receptor alpha (RARA) expression levels, promising effects are demonstrated by the next-generation RAR agonist tamibarotene, which restores differentiation or induces apoptosis.

Systematic assessment of tumor necrosis at baseline in cervical cancer - An independent factor associated with poor outcome.

Cervical cancer (CC) is a leading challenge in oncology worldwide, with high prevalence and mortality rates in young adults, most prominent in low to middle-income countries with marginal screening facilities. From the prospectively collected BioRAIDS (NCT02428842) cohort of primary squamous CC conducted in 7 European countries, a central pathology review was carried out on 294 patients' tumors. The focus was on identification of tumor-stromal characteristics such as CD8, CD45, CD68 staining cells, PD-L1 expression, tumor infiltrating lymphocytes (TILs) together with the degree of tumor necrosis.

Phase Ib study of sabatolimab (MBG453), a novel immunotherapy targeting TIM-3 antibody, in combination with decitabine or azacitidine in high- or very high-risk myelodysplastic syndromes.

The safety and efficacy of sabatolimab, a novel immunotherapy targeting T-cell immunoglobulin domain and mucin domain-3 (TIM-3), was assessed in combination with hypomethylating agents (HMAs) in patients with HMA-naive revised International Prognostic System Score (IPSS-R) high- or very high-risk myelodysplastic syndromes (HR/vHR-MDS) or chronic myelomonocytic leukemia (CMML). Sabatolimab + HMA had a safety profile similar to that reported for HMA alone and demonstrated durable clinical responses in patients with HR/vHR-MDS. These results support the ongoing evaluation of sabatolimab-based combination therapy in MDS, CMML, and acute myeloid leukemia.

Inotuzumab Ozogamicin as Induction Therapy for Patients Older Than 55 Years With Philadelphia Chromosome-Negative B-Precursor ALL.

Purpose: Despite recent advances in adapting the intensity of treatment for older patients with ALL, current protocols are associated with high rates of early deaths, treatment-related toxicity, and dismal prognosis. We evaluated inotuzumab ozogamicin and dexamethasone (Dex) as induction therapy in older patients with ALL within the German Multicenter Study Group for Adult ALL (GMALL).

Patients And Methods: The open-label, multicenter, phase II, INITIAL-1 trial enrolled 45 patients older than 55 years with newly diagnosed, CD22-positive, -negative B-precursor ALL (B-ALL).

Mutated IKZF1 is an independent marker of adverse risk in acute myeloid leukemia.

Genetic lesions of IKZF1 are frequent events and well-established markers of adverse risk in acute lymphoblastic leukemia. However, their function in the pathophysiology and impact on patient outcome in acute myeloid leukemia (AML) remains elusive. In a multicenter cohort of 1606 newly diagnosed and intensively treated adult AML patients, we found IKZF1 alterations in 45 cases with a mutational hotspot at N159S.

RAIDS atlas of significant genetic and protein biomarkers in cervical cancer.

Loss of function in epigenetic acting genes together with driver alterations in the PIK3CA pathway have been shown significantly associated with poor outcome in cervical squamous cell cancer. More recently, a CoxBoost analysis identified 16 gene alterations and 30 high level activated proteins to be of high interest, due to their association with either good or bad outcome, in the context of treatment received by chemoradiation. The objectives here were to review and confirm the significance of these molecular alterations as suggested by literature reports and to pinpoint alternate treatments options for poor-responders to chemoradiation.

Cell fate determinant Llgl1 is required for propagation of acute myeloid leukemia.

Scribble complex proteins can influence cell fate decisions and self-renewal capacity of hematopoietic cells. While specific cellular functions of Scribble complex members are conserved in mammalian hematopoiesis, they appear to be highly context dependent. Using CRISPR/Cas9-based genetic screening, we have identified Scribble complex-related liabilities in AML including LLGL1.