Finerenone attenuates downregulation of the kidney GLP-1 receptor and glucagon receptor and cardiac GIP receptor in mice with comorbid diabetes.

Background: Several new treatments have recently been shown to have heart and kidney protective benefits in people with diabetes. Because these treatments were developed in parallel, it is unclear how the different molecular pathways affected by the therapies may overlap. Here, we examined the effects of the mineralocorticoid receptor antagonist finerenone in mice with comorbid diabetes, focusing on the regulation of expression of the glucagon-like peptide-1 receptor (GLP-1R), gastric inhibitory polypeptide receptor (GIPR) and glucagon receptor (GCGR), which are targets of approved or investigational therapies in diabetes.

Impact of induction regimens intensity and allogeneic stem cell transplantation on survival of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: A multi-institutional study.

Intensive chemotherapy (IC) combination with second- or third-generation TKI improves survival compared to non-IC with first-generation TKI. Allo-HCT was suggestive of improving RFS/OS after propensity score matching and multivariable analysis.

Patient, family and caregiver engagement in diabetes care: a scoping review protocol.

Introduction: New treatments and technologies have advanced diabetes care; however, diabetes continues to have a major impact on the daily lives of affected individuals, especially among equity-deserving groups. Evidence from patient engagement literature suggests that involving diverse patients in healthcare can create cost-effective improvements and enhanced efficiency in care that has high patient acceptability and numerous health benefits, as well as improved provider satisfaction. A scoping review will be conducted to provide a cohesive and comprehensive understanding of patient engagement practices and the resulting outcomes.

Impact of prior inotuzumab ozogamicin treatment on brexucabtagene autoleucel outcomes in adults with B-cell ALL.

The effect of prior inotuzumab ozogamicin (InO) treatment on brexucabtagene autoleucel (brexu-cel) outcomes remains unclear in adults with acute lymphoblastic leukemia (ALL). We conducted a retrospective multicenter analysis of 189 patients with relapsed/refractory ALL treated with brexu-cel. Over half of the patients received InO before brexu-cel (InO exposed).

Inotuzumab ozogamicin in adult acute lymphoblastic leukemia: Development, current status, and future directions.

Inotuzumab ozogamicin (InO) is an antibody-drug conjugate approved for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (ALL). Several clinical trials are investigating InO in combination with low-intensity chemotherapy or other anti-ALL-targeted therapies in the salvage and frontline settings, notably in older adults who often cannot tolerate intensive chemotherapy and tend to have higher-risk disease. InO is also increasingly used to bridge patients to hematopoietic stem cell transplantation (HSCT), in sequence with chimeric antigen receptor T-cell therapy, to eliminate measurable residual disease and to prevent post-HSCT relapse.

Blinatumomab for MRD-Negative Acute Lymphoblastic Leukemia in Adults.

Background: Many older adults with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) have a relapse despite having a measurable residual disease (MRD)-negative complete remission with combination chemotherapy. The addition of blinatumomab, a bispecific T-cell engager molecule that is approved for the treatment of relapsed, refractory, and MRD-positive BCP-ALL, may have efficacy in patients with MRD-negative remission.

Methods: In a phase 3 trial, we randomly assigned patients 30 to 70 years of age with -negative BCP-ALL (with :: indicating fusion) who had MRD-negative remission (defined as <0.

Effect of hyperglycemia and empagliflozin on markers of cardiorenal injury and inflammation in patients with type 1 diabetes.

Aims: To investigate the effect of hyperglycemia and empagliflozin on cardiorenal injury and inflammation in patients with uncomplicated type 1 diabetes (T1D).

Methods: Serum cardiac (sST2, Gal-3, cTnT), kidney injury (KIM-1, NGAL), inflammatory (sTNFR1, sTNFR2), and hemodynamic (NT-proBNP, EPO) markers were assessed post-hoc in two separate T1D cohorts. The glycemic clamp trial (NCT02344602) evaluated 49 adults with T1D and 27 controls under euglycemic and acute hyperglycemic conditions.

Interferons and interferon-related pathways in heart disease.

Interferons (IFNs) and IFN-related pathways play key roles in the defence against microbial infection. However, these processes may also be activated during the pathogenesis of non-infectious diseases, where they may contribute to organ injury, or function in a compensatory manner. In this review, we explore the roles of IFNs and IFN-related pathways in heart disease.

Association of leukemic molecular profile with efficacy of inotuzumab ozogamicin in adults with relapsed/refractory ALL.

The phase 3 INO-VATE trial demonstrated higher rates of remission, measurable residual disease negativity, and improved overall survival for patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) who received inotuzumab ozogamicin (InO) vs standard-of-care chemotherapy (SC). Here, we examined associations between genomic alterations and the efficacy of InO. Of 326 randomized patients, 91 (InO, n = 43; SC, n = 48) had samples evaluable for genomic analysis.

Efficacy and safety of mitoxantrone, etoposide, and cytarabine for treatment of relapsed or refractory acute myeloid leukemia.

Background/rationale: Most patients with acute myeloid leukemia (AML) develop relapsed or refractory (R/R) disease after receiving initial induction chemotherapy. Salvage chemotherapy followed by allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only curative therapy for R/R AML. Mitoxantrone, etoposide, and cytarabine (MEC) is the current standard of care salvage regimen for R/R AML at Cleveland Clinic.

Characteristics of Health Care Settings Where Adolescents and Young Adults Receive Care for ALL.

Purpose: Individuals diagnosed with cancer between 15 and 39 years (adolescent and young adult [AYA]) face unique vulnerability. Detail is lacking about care delivery for these patients, especially those with ALL. We address these knowledge gaps by describing AYA ALL care delivery details at National Cancer Institute Community Oncology Research Program (NCORP) (sub)affiliates by model of care.

Minireview: Understanding and targeting inflammatory, hemodynamic and injury markers for cardiorenal protection in type 1 diabetes.

The coexistence of cardiovascular disease (CVD) and diabetic kidney disease (DKD) is common in people with type 1 diabetes (T1D) and is strongly associated with an increased risk of morbidity and mortality. Hence, it is imperative to explore robust tools that can accurately reflect the development and progression of cardiorenal complications. Several cardiovascular and kidney biomarkers have been identified to detect at-risk individuals with T1D.

SINGLE CELL DISSECTION OF DEVELOPMENTAL ORIGINS AND TRANSCRIPTIONAL HETEROGENEITY IN B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA.

Sequencing of bulk tumor populations has improved genetic classification and risk assessment of B-ALL, but does not directly examine intratumor heterogeneity or infer leukemia cellular origins. We profiled 89 B-ALL samples by single-cell RNA-seq (scRNA-seq) and compared them to a reference map of normal human B-cell development established using both functional and molecular assays. Intra-sample heterogeneity was driven by cell cycle, metabolism, differentiation, and inflammation transcriptional programs.

Glucagon-like peptide-1 receptor signaling modifies the extent of diabetic kidney disease through dampening the receptor for advanced glycation end products-induced inflammation.

Glucagon like peptide-1 (GLP-1) is a hormone produced and released by cells of the gastrointestinal tract following meal ingestion. GLP-1 receptor agonists (GLP-1RA) exhibit kidney-protective actions through poorly understood mechanisms. Here we interrogated whether the receptor for advanced glycation end products (RAGE) plays a role in mediating the actions of GLP-1 on inflammation and diabetic kidney disease.

Response-adapted, time-limited venetoclax, umbralisib, and ublituximab for relapsed/refractory chronic lymphocytic leukemia.

Many patients with chronic lymphocytic leukemia (CLL) will develop treatment resistance to Bruton tyrosine kinase (BTK) inhibitors. Phosphatidylinositol-3-kinase (PI3K) inhibitors, including umbralisib, have significant clinical activity in relapsed/refractory CLL, but prolonged exposure is associated with potential toxicities. Owing to the synergistic antitumor effects of combined PI3K and BCL-2 inhibition, we sought to explore the feasibility of response-adapted, time-limited therapy to optimize disease control while mitigating the risks of prolonged treatment.

Altered expression, but small contribution, of the histone demethylase KDM6A in obstructive uropathy in mice.

Epigenetic processes have emerged as important modulators of kidney health and disease. Here, we studied the role of KDM6A (a histone demethylase that escapes X-chromosome inactivation) in kidney tubule epithelial cells. We initially observed an increase in tubule cell Kdm6a mRNA in male mice with unilateral ureteral obstruction (UUO).

Preventing occludin tight-junction disruption via inhibition of microRNA-193b-5p attenuates viral load and influenza-induced lung injury.

Virus-induced lung injury is associated with loss of pulmonary epithelial-endothelial tight junction integrity. While the alveolar-capillary membrane may be an indirect target of injury, viruses may interact directly and/or indirectly with miRs to augment their replication potential and evade the host antiviral defense system. Here, we expose how the influenza virus (H1N1) capitalizes on host-derived interferon-induced, microRNA (miR)-193b-5p to target occludin and compromise antiviral defenses.

Patterns of Diagnostic Evaluation and Determinants of Treatment in Older Patients With Non-transfusion Dependent Myelodysplastic Syndromes.

Background: Older patients with myelodysplastic syndromes (MDS), particularly those with no or one cytopenia and no transfusion dependence, typically have an indolent course. Approximately, half of these receive the recommended diagnostic evaluation (DE) for MDS. We explored factors determining DE in these patients and its impact on subsequent treatment and outcomes.

Pressure overload induces ISG15 to facilitate adverse ventricular remodeling and promote heart failure.

Inflammation promotes adverse ventricular remodeling, a common antecedent of heart failure. Here, we set out to determine how inflammatory cells affect cardiomyocytes in the remodeling heart. Pathogenic cardiac macrophages induced an IFN response in cardiomyocytes, characterized by upregulation of the ubiquitin-like protein IFN-stimulated gene 15 (ISG15), which posttranslationally modifies its targets through a process termed ISGylation.

Single cell G-protein coupled receptor profiling of activated kidney fibroblasts expressing transcription factor 21.

Background And Purpose: Activated fibroblasts deposit fibrotic matrix in chronic kidney disease (CKD) and G-protein coupled receptors (GPCRs) are the most druggable therapeutic targets. Here, we set out to establish a transcriptional profile that identifies activated kidney fibroblasts and the GPCRs that they express.

Experimental Approach: RNA sequencing and single cell qRT-PCR were performed on mouse kidneys after unilateral ureteral obstruction (UUO).

The anti-hypertensive effects of sodium-glucose cotransporter-2 inhibitors.

Introduction: Hypertension is a well-established risk factor for cardiovascular (CV) events in patients with chronic kidney disease (CKD), heart failure, obesity, and diabetes. Despite the usual prescribed antihypertensive therapies, many patients fail to achieve the recommended blood pressure (BP) targets.

Areas Covered: This review summarizes the clinical BP-lowering data presented in major CV and kidney outcome trials for sodium-glucose cotransporter-2 (SGLT2) inhibitors, as well as smaller dedicated BP trials in high-risk individuals with and without diabetes.

When will chemotherapy be replaced in upfront induction therapy for adult acute lymphoblastic leukemia (ALL)?

The treatment of acute lymphoblastic leukemia (ALL) has changed significantly over the last decade. With the approval of novel antibody based therapies in the relapsed/refractory setting, many of these agents are starting to be used in the upfront setting in clinical trials for older patients. These results have been impressive, and further trials are underway.