p53 and p16 expression profiles in vulvar cancer: a translational analysis by the Arbeitsgemeinschaft Gynäkologische Onkologie Chemo and Radiotherapy in Epithelial Vulvar Cancer study group.

Background: There are 2 known pathways for tumorigenesis of vulvar squamous cell carcinoma-a human papillomavirus-dependent pathway characterized by p16 overexpression and a human papillomavirus-independent pathway linked to lichen sclerosus, characterized by TP53 mutation. A correlation of human papillomavirus dependency with a favorable prognosis has been proposed.

Objective: The objective of the study was to further understand the role of human papillomavirus and p53 status in vulvar squamous cell carcinoma and characterize its clinical relevance.

High cut-off dialysis mitigates pro-calcific effects of plasma on vascular progenitor cells.

Mortality of patients with end-stage renal disease tremendously exceeds that of the general population due to excess cardiovascular morbidity. Large middle-sized molecules (LMM) including pro-inflammatory cytokines are major drivers of uremic cardiovascular toxicity and cannot be removed sufficiently by conventional high-flux (HFL) hemodialysis. We tested the ability of plasma from 19 hemodialysis patients participating in a trial comparing HFL with high cut-off (HCO) membranes facilitating removal of LMM to induce calcification in mesenchymal stromal cells (MSC) functioning as vascular progenitors.

B cell depletion and signs of sepsis-acquired immunodeficiency in bone marrow and spleen of COVID-19 deceased.

Objectives: In coronavirus disease 2019 (COVID-19), the adaptive immune response is of considerable importance, and detailed cellular immune reactions in the hematological system of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are yet to be clarified.

Methods: This study reports the morphological characterization of both bone marrow and spleen in 11 COVID-19 decedents with respect to findings in the peripheral blood and pulmonary SARS-CoV-2 burden.

Results: In the bone marrow, activation and left shift were found in at least 55% of patients, which was mirrored by peripheral anaemia, granulocytic immaturity and multiple thromboembolic events.

Complications after CD19+ CAR T-Cell Therapy.

Clinical trials demonstrated that CD19+ chimeric antigen receptor (CAR) T-cells can be highly effective against a number of malignancies. However, the complete risk profile of CAR T-cells could not be defined in the initial trials. Currently, there is emerging evidence derived from post approval studies in CD19+ CAR T-cells demonstrating both short-term and medium-term effects, which were unknown at the time of regulatory approval.

Clinical outcome of older adults with acute myeloid Leukemia: An analysis of a large tertiary referral Center over two decades.

Objective: In older adults with acute myeloid leukemia (AML), the overall outcome is still dismal and long-term data on survival are scarce, particularly outside of clinical trials. Here, we assess characteristics, prognostic factors and long-term survival in patients ≥60 years who were treated for AML at our center over the past 17 years.

Methods: 590 older adults with newly diagnosed AML were characterized according to Eastern Cooperative Oncology Group (ECOG) score, Charlson comorbidity index (CCI), European LeukemiaNet (ELN) risk, type of therapy, serum ferritin (SF) and further baseline characteristics.

ERRα inhibitor acts as a potential agonist of PPARγ to induce cell apoptosis and inhibit cell proliferation in endometrial cancer.

Two transcriptional factors, peroxisome proliferator-activated receptor-γ (PPARγ) and estrogen-related receptor-α (ERRα), have been reported to be key regulators of cellular energy metabolism. However, the relationship between ERRα and PPARγ in the development of endometrial cancer (EC) is still unclear. The expression levels of PPARγ and ERRα in EC were evaluated by quantitative real-time PCR, western blot, tissue array and immunohistochemistry.

Management of Acute Myocarditis and Chronic Inflammatory Cardiomyopathy: An Expert Consensus Document.

Myocarditis is an inflammatory disease of the heart that may occur because of infections, immune system activation, or exposure to drugs. The diagnosis of myocarditis has changed due to the introduction of cardiac magnetic resonance imaging. We present an expert consensus document aimed to summarize the common terminology related to myocarditis meanwhile highlighting some areas of controversies and uncertainties and the unmet clinical needs.

Case Report First-in-Man Method Description: Left Ventricular Unloading With iVAC2L During Veno-Arterial Extracorporeal Membrane Oxygenation: From Veno-Arterial Extracorporeal Membrane Oxygenation to ECMELLA to EC-iVAC®.

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is increasingly used in bi-ventricular failure with cardiogenic shock to maintain systemic perfusion. Nonetheless, it tends to increase left ventricular (LV) afterload and myocardial oxygen demand. In order to mitigate these negative effects on the myocardium, an Impella CP® (3.

Factor H-related protein 1: a complement regulatory protein and guardian of necrotic-type surfaces.

Factor H-related protein 1 (FHR-1) is a member of the factor H protein family, which is involved in regulating innate immune complement reactions. Genetic modification of the encoding gene, CFHR1 on human chromosome 1, is involved in diseases such as age-related macular degeneration, C3 glomerulopathy and atypical haemolytic uraemic syndrome, indicating an important role for FHR-1 in human health. Recent research data demonstrate that FHR-1 levels increase in IgA nephropathy and anti-neutrophilic cytoplasmic autoantibodies (ANCA) vasculitis and that FHR-1 induces strong inflammation in monocytes on necrotic-type surfaces, suggesting a complement-independent role.

Real-Life Multimarker Monitoring in Patients with Heart Failure: Continuous Remote Monitoring of Mobility and Patient-Reported Outcomes as Digital End Points in Future Heart-Failure Trials.

Aims: Heart failure (HF) affects approximately 26 million people worldwide. With an aging global population, innovative approaches to HF evaluation and management are needed to cope with the worsening HF epidemic. The aim of the Real-Life Multimarker Monitoring in Patients with Heart Failure (REALIsM-HF) study (NCT03507439) is to evaluate a composite instrument comprising remote, real-time, activity-monitoring devices combined with daily electronic patient-reported outcome (ePRO) items in patients who have been hospitalized for HF and are undergoing standard HF assessment (e.

Myocarditis and inflammatory cardiomyopathy: current evidence and future directions.

Inflammatory cardiomyopathy, characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function, has a heterogeneous aetiology. Inflammatory cardiomyopathy is predominantly mediated by viral infection, but can also be induced by bacterial, protozoal or fungal infections as well as a wide variety of toxic substances and drugs and systemic immune-mediated diseases. Despite extensive research, inflammatory cardiomyopathy complicated by left ventricular dysfunction, heart failure or arrhythmia is associated with a poor prognosis.

Long-term results of robotic radiosurgery for non brachytherapy patients with cervical cancer.

Background: Consolidation brachytherapy is a critical treatment component for cervical cancer patients undergoing primary chemoradiation. Some patients are unsuitable for brachytherapy for a variety of reasons. The use of alternatives (LINAC-based stereotactic radiosurgery or external beam boosts) compromise oncologic results in cervical cancer patients.

Disease progression patterns and risk factors associated with mortality in deceased patients with COVID-19 in Hubei Province, China.

Background: Detailed descriptions of the patterns of disease progression of deceased coronavirus disease 2019 (COVID-19) patients have not been well explored.

Objectives: This study sought to explore disease progression patterns and risk factors associated with mortality of deceased patients with COVID-19.

Materials And Methods: Epidemiological, clinical, laboratory, and imaging data (from 15 January to 26 March 2020) of laboratory-confirmed COVID-19 patients were collected retrospectively from two hospitals, Hubei province, China.

Head-to-head comparison of cardiovascular MR feature tracking cine versus acquisition-based deformation strain imaging using myocardial tagging and strain encoding.

Purpose: Myocardial feature-tracking (FT) deformation imaging is superior for risk stratification compared with volumetric approaches. Because there is no clear recommendation regarding FT postprocessing, we compared different FT-strain analyses with reference standard techniques, including tagging and strain-encoded (SENC) MRI.

Methods: Feature-tracking software from four different vendors (TomTec, Medis, Circle [CVI], and Neosoft), tagging (Segment), and fastSENC (MyoStrain) were used to determine left ventricular global circumferential strains (GCS) and longitudinal strains (GLS) in 12 healthy volunteers and 12 patients with heart failure.

Reduced Calcium Signaling Is Associated With Severe Graft-Versus-Host Disease: Results From Preclinical Models and From a Prospective EBMT Study.

Despite its involvement in various immune functions, including the allogeneic activation of T-lymphocytes, the relevance of calcium (Ca) for GVHD pathobiology is largely unknown. To elucidate a potential association between Caand GVHD, we analyzed Ca-sensing G-protein coupled receptor 6a (GPRC6a) signaling in preclinical GVHD models and conducted a prospective EBMT study on Ca serum levels prior alloSCT including 363 matched sibling allogeneic peripheral blood stem cell transplantations (alloSCTs). In experimental models, we found decreased expression during intestinal GVHD.

Early conversion to a CNI-free immunosuppression with SRL after renal transplantation-Long-term follow-up of a multicenter trial.

Introduction: Early conversion to a CNI-free immunosuppression with SRL was associated with an improved 1- and 3- yr renal function as compared with a CsA-based regimen in the SMART-Trial. Mixed results were reported on the occurrence of donor specific antibodies under mTOR-Is. Here, we present long-term results of the SMART-Trial.

NAFLD and cardiovascular diseases: a clinical review.

Non-alcoholic fatty liver DISEASE (NAFLD) is the most common chronic liver disease in Western countries and affects approximately 25% of the adult population. Since NAFLD is frequently associated with further metabolic comorbidities such as obesity, type 2 diabetes mellitus, or dyslipidemia, it is generally considered as the hepatic manifestation of the metabolic syndrome. In addition to its potential to cause liver-related morbidity and mortality, NAFLD is also associated with subclinical and clinical cardiovascular disease (CVD).

Post-operative management and follow-up of surgical treatment in the case of rectovaginal and retrocervical endometriosis.

Introduction: Deep infiltrating endometriosis (DIE) affects between 3.8% and 37% of all endometriosis patients, mostly affecting rectovaginal septum or retrocervical space and characterized by the severe endometriosis-related complaints. Nowadays, generally managed with surgery.

A Genetics-First Approach Revealed Monogenic Disorders in Patients With ARM and VACTERL Anomalies.

The VATER/VACTERL association (VACTERL) is defined as the non-random occurrence of the following congenital anomalies: Vertebral, Anal, Cardiac, Tracheal-Esophageal, Renal, and Limb anomalies. As no unequivocal candidate gene has been identified yet, patients are diagnosed phenotypically. The aims of this study were to identify patients with monogenic disorders using a genetics-first approach, and to study whether variants in candidate genes are involved in the etiology of VACTERL or the individual features of VACTERL: Anorectal malformation (ARM) or esophageal atresia with or without trachea-esophageal fistula (EA/TEF).

Intestinal Virome Signature Associated With Severity of Nonalcoholic Fatty Liver Disease.

Background & Aims: Alterations in the gut microbiome have been associated with the severity of nonalcoholic fatty liver disease (NAFLD). Previous studies focused exclusively on the bacteria in the microbiome; we investigated changes in the viral microbiome (virome) in patients with NAFLD.

Methods: In a prospective, cross-sectional, observational study, we extracted RNA and DNA virus-like particles from fecal samples from 73 patients with NAFLD: 29 patients had an NAFLD Activity Score (NAS) of 0-4, 44 patients had an NAS of 5-8 or liver cirrhosis (LCI), 37 patients had F0-F1 fibrosis, and 36 patients had F2-F4 fibrosis.

Splenic Switch-Off for Determining the Optimal Dosage for Adenosine Stress Cardiac MR in Terms of Stress Effectiveness and Patient Safety.

Background: Adenosine stress MRI is well established for the evaluation of known and suspected coronary artery disease. However, a proportion of patients might be "under-stressed" using the standard adenosine dose.

Purpose: To compare three different adenosine dosages for stress MRI in terms of stress adequacy based on splenic switch-off (SSO) and limiting side effects.

The NLRP3 Inflammasome in Alcoholic and Nonalcoholic Steatohepatitis.

Nonalcoholic steatohepatitis (NASH) and alcoholic hepatitis (ASH) are advanced forms of fatty liver diseases that are associated with a high morbidity and mortality worldwide. Patients with ASH or NASH are more susceptible to the progression of fibrosis and cirrhosis up to the development of hepatocellular carcinoma. Currently, there are limited medical therapies available.