Gut microbiome correlates of response and toxicity following anti-CD19 CAR T cell therapy.

Anti-CD19 chimeric antigen receptor (CAR) T cell therapy has led to unprecedented responses in patients with high-risk hematologic malignancies. However, up to 60% of patients still experience disease relapse and up to 80% of patients experience CAR-mediated toxicities, such as cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. We investigated the role of the intestinal microbiome on these outcomes in a multicenter study of patients with B cell lymphoma and leukemia.

Paracrine signal emanating from stressed cardiomyocytes aggravates inflammatory microenvironment in diabetic cardiomyopathy.

Myocardial inflammation contributes to cardiomyopathy in diabetic patients through incompletely defined underlying mechanisms. In both human and time-course experimental samples, diabetic hearts exhibited abnormal ER, with a maladaptive shift over time in rodents. Furthermore, as a cardiac ER dysfunction model, mice with cardiac-specific p21-activated kinase 2 (PAK2) deletion exhibited heightened myocardial inflammatory response in diabetes.

Venetoclax in combination with hypomethylating agents or low dose cytarabine for relapsed and refractory acute myeloid leukemia.

Limited treatment options exist for patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). Venetoclax (VEN) in combination with a hypomethylating agent (HMA) or low-dose cytarabine (LDAC) has been recently approved for treatment-naïve patients unfit for intensive induction. Limited data are available to characterize the efficacy of VEN combinations in R/R AML.

Day 4 vs. day 12 G-CSF administration following reduced intensity peripheral blood allogeneic stem cell transplant.

Introduction: Granulocyte colony-stimulating factor (G-CSF) hastens neutrophil engraftment and reduces infections after allogeneic hematopoietic cell transplant (alloHCT), yet the optimal start date is unknown. Additionally, concurrent G-CSF and methotrexate for graft-vs-host disease (GVHD) prophylaxis may potentiate myelosuppression, and prolonged G-CSF is costly. Our institution changed from day + 4 to day + 12 G-CSF initiation following reduced intensity (RIC) alloHCT with methotrexate GVHD prophylaxis.

Letermovir vs. high-dose valacyclovir for cytomegalovirus prophylaxis following haploidentical or mismatched unrelated donor allogeneic hematopoietic cell transplantation receiving post-transplant cyclophosphamide.

Patients undergoing haploidentical or mismatched unrelated donor (haplo/MMUD) allogeneic hematopoietic cell transplantation (alloHCT) receiving post-transplant cyclophosphamide (PTCy) are at high risk of cytomegalovirus (CMV) infection. Experience with letermovir (LET) in this population is limited. This single center retrospective cohort study compared CMV and transplant outcomes between LET and a historical control with high-dose valacyclovir (HDV) prophylaxis in adults undergoing haplo/MMUD alloHCT.

Diagnostic performance and predictive value of D-dimer testing in patients referred to the emergency department for suspected myocardial infarction.

Purpose: The study sought to assess the performance of D-dimer testing for the diagnosis of acute coronary syndrome (ACS) and prediction of outcomes in patients admitted for suspected myocardial infarction (MI).

Results: A total of 3,557 patients with suspected ACS presenting to a single center with a broad range of symptoms including atypical chest pain were retrospectively recruited between 02/2012-01/2019. Of the study cohort, 435 patients had unstable angina (UA), 420 non-ST-segment elevation myocardial infarction (NSTEMI), 22 ST-segment elevation myocardial infarction (STEMI), and 2,680 non-coronary chest pain.

[Deep vein thrombosis as a primary symptom of abdominal aortic aneurysm : Bilateral deep vein thrombosis caused by infrarenal abdominal aortic aneurysm (15 cm in diameter) with complete compression of the inferior vena cava].

This article presents the case of a 70-year-old obese patient with severe bilateral leg pain due to deep vein thrombosis. After unsuccessful venous recanalization, computed tomography angiography revealed an abdominal aortic aneurysm 15 cm in diameter with total compression of the inferior vena cava. For venous decompression as well as rupture prophylaxis, conventional open surgical repair was performed.

One-year results following PASCAL-based or MitraClip-based mitral valve transcatheter edge-to-edge repair.

Aims: Mitral valve transcatheter edge-to-edge repair (TEER) has been established as a suitable alternative to mitral valve surgery in patients with severe mitral regurgitation (MR) and high surgical risk. The PASCAL system represents a novel device, potentially augmenting the toolkit for TEER. The aim of this study was to assess and compare short and 1 year safety and efficacy of the PASCAL and MitraClip systems for TEER.

Functional improvement following direct interventional leaflet repair of severe tricuspid regurgitation.

Aims: Several new percutaneous tricuspid repair systems have recently been introduced as new treatment options for severe tricuspid regurgitation (TR). Clinical improvement following percutaneous tricuspid valve leaflet repair has been demonstrated by recent studies. A possible impact on exercise capacity has not yet been reported.

[Drop in oxygen saturation and blood pressure as well as increase in central venous pressure during mitral valve clipping in an 81-year-old female patient].

Background: Atrial septal defects (ASD) following endovascular mitral valve clipping are potentially hemodynamically relevant complications. Immediate closure with an occluder can represent a safe and effective treatment. An 81-year-old female patient suffering from severe dyspnea due to previously known severe mitral valve regurgitation was scheduled for elective mitral valve clipping.

Decade-long leukaemia remissions with persistence of CD4 CAR T cells.

The adoptive transfer of T lymphocytes reprogrammed to target tumour cells has demonstrated potential for treatment of various cancers. However, little is known about the long-term potential and clonal stability of the infused cells. Here we studied long-lasting CD19-redirected chimeric antigen receptor (CAR) T cells in two patients with chronic lymphocytic leukaemia who achieved a complete remission in 2010.

Disease Modeling and Model-Based Meta-Analyses to Define a New Direction for a Phase III Program of Gantenerumab in Alzheimer's Disease.

Selecting the right dose is a significant challenge in designing clinical development programs, especially for slowly progressing diseases lacking predictive biomarkers of efficacy that may require long-term treatment to assess clinical benefit. Gantenerumab, a fully human monoclonal antibody (mAb) that binds to aggregated amyloid-beta, was tested in two 24-month phase III studies (NCT01224106, NCT02051608) in participants with prodromal and mild Alzheimer's disease (AD), respectively. Dosing in the first phase III study was suspended after a preplanned interim futility analysis in 2014.

HFA-PEFF score: prognosis in patients with preserved ejection fraction after transcatheter aortic valve implantation.

Aims: Many transcatheter aortic valve implantation (TAVI) candidates have underlying heart failure with preserved ejection fraction (HFpEF) in addition to symptomatic aortic stenosis. Diagnosis of HFpEF is challenging. The Heart Failure Association of the European Society of Cardiology proposed the HFA-PEFF score as part of a novel diagnostic algorithm.

The orphan receptor GPRC5B activates pro-inflammatory signaling in the vascular wall via Fyn and NFκB.

Background And Aims: Atherosclerosis is driven by an inflammatory process of the vascular wall. The novel orphan G-protein coupled receptor 5B of family C (GPRC5B) is involved in drosophila sugar and lipid metabolism as well as mice adipose tissue inflammation. Here, we investigated the role of GPRC5B in the pro-atherogenic mechanisms of hyperglycemia and vascular inflammation.

BAMM (BRAF Autophagy and MEK Inhibition in Melanoma): A Phase I/II Trial of Dabrafenib, Trametinib, and Hydroxychloroquine in Advanced BRAFV600-mutant Melanoma.

Purpose: Autophagy is a resistance mechanism to BRAF/MEK inhibition in BRAFV600-mutant melanoma. Here we used hydroxychloroquine (HCQ) to inhibit autophagy in combination with dabrafenib 150 mg twice daily and trametinib 2 mg every day (D+T).

Patients And Methods: We conducted a phase I/II clinical trial in four centers of HCQ + D+T in patients with advanced BRAFV600-mutant melanoma.

Impact of Homoarginine on Myocardial Function and Remodeling in a Rat Model of Chronic Renal Failure.

Purpose: Low plasma concentrations of the amino acid homoarginine (HA) have been shown to correlate with adverse cardiovascular outcome, particularly in patients with chronic kidney disease. The present study sought to investigate the effect of HA treatment on cardiac remodeling in rats undergoing artificially induced renal insufficiency by 5/6 nephrectomy (5/6 Nx).

Methods: A total of 33 male Wistar rats were randomly divided into sham and 5/6 Nx groups, receiving either placebo treatment or 400 mg·kg·day HA over a 4-week period.

[Guidelines of the European Resuscitation Council (ERC) on cardiopulmonary resuscitation 2021: update and comments].

The European guidelines on cardiopulmonary resuscitation, which are divided into 12 chapters, have recently been published. In addition to the already known chapters, the topics "epidemiology" and "life-saving systems" have been integrated for the first time. For each chapter five practical key statements were formulated.

Low-Level Elevations of Procalcitonin Are Associated with Increased Mortality in Acute Heart Failure Patients, Independent of Concomitant Infection.

We aimed to evaluate the prognostic value of procalcitonin (PCT) in acute heart failure (AHF) patients, especially in those without underlying infection. We enrolled patients presenting with acute dyspnea to the emergency department (ED) of Heidelberg University Hospital and studied the prognostic role of PCT on all-cause death. Of 312 patients, AHF was diagnosed in 139 patients.

Risk Factors, Treatment and Prognosis of Patients with Lung Cancer after Heart Transplantation.

Long-term survival after heart transplantation (HTX) is impacted by adverse effects of immunosuppressive pharmacotherapy, and post-transplant lung cancer is a common occurrence. This study aimed to examine the risk factors, treatment, and prognosis of patients with post-transplant lung cancer. We included 625 adult patients who received HTX at Heidelberg Heart Center between 1989 and 2018.

Dynamic Handgrip Exercise: Feasibility and Physiologic Stress Response of a Potential Needle-Free Cardiac Magnetic Resonance Stress Test.

Cardiac magnetic resonance (CMR) pharmacological stress-testing is a well-established technique for detecting myocardial ischemia. Although stressors and contrast agents seem relatively safe, contraindications and side effects must be considered. Substantial costs are further limiting its applicability.

Cancer-A Major Cardiac Comorbidity With Implications on Cardiovascular Metabolism.

Cardiovascular diseases have multifactorial causes. Classical cardiovascular risk factors, such as arterial hypertension, smoking, hyperlipidemia, and diabetes associate with the development of vascular stenoses and coronary heart disease. Further comorbidities and its impact on cardiovascular metabolism have gotten more attention recently.

Relapsed ALL: CAR T vs transplant vs novel therapies.

Chimeric antigen receptor T-cell therapy targeting CD19 (CART19) has expanded the treatment options for patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (ALL). The approval of tisagenlecleucel for pediatric and young adult patients with r/r ALL has allowed broader access for some patients, but the treatment of older adults is available (at the time of this writing) only within a clinical trial. High remission rates have been consistently observed with varied CART19 products and treatment platforms, but durability of remissions and thus the potential role of a consolidative allogeneic stem cell transplant (SCT) is more uncertain and likely to vary by product and population treated.

Identification of p.C335R Variant in a Large Family with Dilated Cardiomyopathy and Conduction Disease.

Introduction: Familial dilated cardiomyopathy (DCM) is clinically variable and has been associated with mutations in more than 50 genes. Rapid improvements in DNA sequencing have led to the identification of diverse rare variants with unknown significance (VUS), which underlines the importance of functional analyses. In this study, by investigating human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), we evaluated the pathogenicity of the p.