Long-term follow-up of efficacy and safety of selinexor maintenance treatment in patients with TP53wt advanced or recurrent endometrial cancer: A subgroup analysis of the ENGOT-EN5/GOG-3055/SIENDO study.

Objective: To report long-term efficacy and safety of selinexor maintenance therapy in adults with TP53 wild-type (TP53wt) stage IV or recurrent endometrial cancer (EC) who achieved partial remission (PR) or complete remission (CR) following chemotherapy.

Methods: Analysis of the prespecified, exploratory subgroup of patients with TP53wt EC from the phase 3 SIENDO study was performed. Progression-free survival (PFS) benefit in patients with TP53wt EC and across other patient subgroups were exploratory endpoints.

Clinical Practice Guideline: Microhematuria in Children and Young Adults.

Background: Occult blood in the urine, or microhematuria, is a common finding (about 10%) in children and young adults. It is often of brief duration and therefore harmless. In persistent microhematuria, acanthocytes in the urine are a frequently unrecognized early marker of glomerular kidney disease.

Multimodal binding and inhibition of bacterial ribosomes by the antimicrobial peptides Api137 and Api88.

Proline-rich antimicrobial peptides (PrAMPs) inhibit bacterial protein biosynthesis by binding to the polypeptide exit tunnel (PET) near the peptidyl transferase center. Api137, an optimized derivative of honeybee PrAMP apidaecin, inhibits protein expression by trapping release factors (RFs), which interact with stop codons on ribosomes to terminate translation. This study uses cryo-EM, functional assays and molecular dynamic (MD) simulations to show that Api137 additionally occupies a second binding site near the exit of the PET and can repress translation independently of RF-trapping.

ENGOT-EN20/GOG-3083/XPORT-EC-042 - A phase III, randomized, placebo-controlled, double-blind, multicenter trial of selinexor in maintenance therapy after systemic therapy for patients with p53 wild-type, advanced, or recurrent endometrial carcinoma: rationale, methods, and trial design.

Background: Patients with advanced/recurrent endometrial cancer have a poor prognosis and limited treatment options. Biomarkers such as tumor protein 53 () in endometrial cancer can integrate novel strategies for improved and individualized treatment that could impact patient outcomes. In an exploratory analysis of the phase III ENGOT-EN5/GOG-3055/SIENDO study of selinexor maintenance monotherapy 80 mg in advanced/recurrent endometrial cancer, a pre-specified subgroup of patients with wild type (wt) endometrial cancer showed preliminary activity at long-term follow-up with a generally manageable safety profile (median progression-free survival 27.

ESGO-ESMO-ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease.

The European Society of Gynaecological Oncology, the European Society for Medical Oncology (ESMO) and the European Society of Pathology held a consensus conference (CC) on ovarian cancer on 15-16 June 2022 in Valencia, Spain. The CC panel included 44 experts in the management of ovarian cancer and pathology, an ESMO scientific advisor and a methodologist. The aim was to discuss new or contentious topics and develop recommendations to improve and harmonise the management of patients with ovarian cancer.

Gaucher-like Cells in Thalassemia Intermedia: Is It a Challenge?

We describe two cases of thalassemia intermedia (TI) patients with the presence of Gaucher-like cells in hematopoietic tissue biopsies, raising diagnostic dilemmas. The first is a 56-year-old female with bone lesions, splenomegaly, hypochromic microcytic anemia and Gaucher-like cells in the bone marrow, with a final diagnosis of TI, and the second is a 69-year-old male with TI, monoclonal gammopathy of undetermined significance (MGUS) that accelerated to multiple myeloma (MM) requiring treatment, bone disease and Gaucher-like cells in the bone marrow and the spleen, and heterozygoty of Gaucher disease (GD). Gaucher-like cells are difficult to differentiate from true Gaucher cells, that are the hallmark of GD suspicion.

Oral Selinexor as Maintenance Therapy After First-Line Chemotherapy for Advanced or Recurrent Endometrial Cancer.

Purpose: Selinexor inhibits exportin-1 (XPO1) resulting in nuclear accumulation of tumor suppressor proteins including p53 and has clinical activity in endometrial cancer (EC). The primary end point was to assess progression-free survival (PFS) with once-weekly oral selinexor in patients with advanced or recurrent EC.

Patients And Methods: ENGOT-EN5/GOG-3055/SIENDO was a randomized, prospective, multicenter, double-blind, placebo-controlled, phase III study at 107 sites in 10 countries.

Traumatized German soldiers with moral injury - value-based cognitive-behavioral group therapy to treat war-related shame.

Introduction: During deployment, soldiers are confronted with potentially morally injurious events. In many cases, these events violate their personal values and belief systems, resulting in feelings of anger, alienation, guilt, and shame. The psychological distress caused by such transgressions is defined as moral injury.

Digital therapeutic to improve cancer-related well-being: a pilot randomized controlled trial.

Objective: This randomized waitlist controlled pilot study aimed to evaluate the feasibility and preliminary efficacy of Mika, an app-based digital therapeutic intervention hypothesized to improve management and the support of cancer patients.

Methods: Patients with gynecological malignancies undergoing post-operative or routine outpatient chemotherapy were randomized (5:2) into intervention (Mika plus treatment-as-usual) and control (treatment-as-usual alone). Feasibility outcomes including dropout rate, reasons for dropout, and intervention adherence, as well as efficacy outcomes including depression, fatigue, and health literacy were assessed at baseline, 4, 8, and 12 weeks.

Effects of a brief mindfulness meditation practice on Pavlovian-to-instrumental transfer in alcohol use disorder - a pilot study.

Introduction: Pavlovian conditioned contextual cues have been suggested to modulate instrumental action and might explain maladaptive behavior such as relapse in participants suffering from alcohol use disorder (AUD). Pavlovian-to-Instrumental transfer (PIT) experimentally assesses the magnitude of this context-dependent effect and studies have shown a larger PIT effect in AUD populations. Taken this into account, a reduction of the influence of cues on behavior seems warranted and one approach that could alter such cue reactivity is mindfulness.

INOVATYON/ ENGOT-ov5 study: Randomized phase III international study comparing trabectedin/pegylated liposomal doxorubicin (PLD) followed by platinum at progression vs carboplatin/PLD in patients with recurrent ovarian cancer progressing within 6-12 months after last platinum line.

Background: This trial investigated the hypothesis that the treatment with trabectedin/PLD (TP) to extend the platinum-free interval (TFIp) can improve overall survival (OS) in patients with recurrent ovarian cancer (OC).

Methods: Patients with OC (up to two previous platinum-based lines), with a TFIp of 6-12 months, were randomised to receive carboplatin/PLD (CP) or TP followed by platinum therapy at relapse. The primary endpoint was OS (HR: 0.

The attention-emotion interaction in healthy female participants on oral contraceptives during 1-week escitalopram intake.

Previous findings in healthy humans suggest that selective serotonin reuptake inhibitors (SSRIs) modulate emotional processing earlier changes in attention. However, many previous studies have provided inconsistent findings. One possible reason for such inconsistencies is that these studies did not control for the influence of either sex or sex hormone fluctuations.

Iron metabolism regulation in females and males exposed to simulated microgravity: results from the randomized trial Artificial Gravity Bed Rest-European Space Agency (AGBRESA).

Background: Iron metabolism imbalance could contribute to physical deconditioning experienced by astronauts due to its essential role in energy metabolism, cellular respiration, and oxygen transport.

Objectives: In this clinical exploratory study, we wanted to determine whether artificial gravity (AG) training modulated iron metabolism, RBC indices, and body lean mass in healthy male and female participants exposed to head-down tilt (HDT) bed rest, the reference ground-based model of microgravity.

Methods: We recruited 8 healthy female and 16 healthy male participants who were all exposed to HDT bed rest for 60 d.

The State of Microbiology Diagnostic of Prosthetic Joint Infection in Europe: An In-Depth Survey Among Clinical Microbiologists.

Background: This study aims to give an overview on how microbiology diagnosis tests of Prosthetic joint infections (PJI) is performed in Europe, and to explore whether any factor influences the decision on implementing a test.

Methods: An extensive online survey of clinical microbiologists from seven European countries (Belgium, Estonia, Germany, Italy, Netherlands, Switzerland, and Spain). Following items were assessed: (i).

The Interdisciplinary Diagnosis of Rare Diseases.

Background: Patients with rare diseases often undergo a diagnostic odyssey that can last many years until the diagnosis is definitively established. To improve the diagnosis and treatment of these patients, the German National Task Force for Patients With Rare Diseases (Nationales Aktionsbündnis für Menschen mit Seltenen Erkrankungen, NAMSE) has recommended the creation of Rare Disease Centers (RDCs).

Methods: As part of the joint Translate-NAMSE project, sponsored by the G-BA Innovation Fund (G-BA, German Federal Joint Committee), we investigated the performance of RDCs in establishing the diagnosis of patients suspected to have a rare disease.

Discovering a new part of the phenotypic spectrum of Coffin-Siris syndrome in a fetal cohort.

Purpose: Genome-wide sequencing is increasingly being performed during pregnancy to identify the genetic cause of congenital anomalies. The interpretation of prenatally identified variants can be challenging and is hampered by our often limited knowledge of prenatal phenotypes. To better delineate the prenatal phenotype of Coffin-Siris syndrome (CSS), we collected clinical data from patients with a prenatal phenotype and a pathogenic variant in one of the CSS-associated genes.

Dysregulation of Wnt signaling in bone of type 2 diabetes mellitus and diabetic Charcot arthropathy.

Background: Type 2 diabetes mellitus (T2DM) patients show a markedly higher fracture risk and impaired fracture healing when compared to non-diabetic patients. However in contrast to type 1 diabetes mellitus, bone mineral density in T2DM is known to be normal or even regionally elevated, also known as diabetic bone disease. Charcot arthropathy is a severe and challenging complication leading to bone destruction and mutilating bone deformities.

Carbon-mixed dental cement for fixing fiber optic ferrules prevents visually triggered locomotive enhancement in mice upon optogenetic stimulation.

Optogenetics enables activation/silencing of specific neurons with unprecedented temporal and spatial resolution. The method, however, is prone to artefacts associated with biophysics of light used for illuminating opsin-expressing neurons. Here we employed Tph2-mhChR2-YFP transgenic mice, which express channelrhodopsin (ChR2) only in serotonergic neurons in the brain, to investigate behavioral effects of optogenetic stimulation of serotonergic neurons.

Validity and Reliability of the German Version of the CP QOL-Child and CP QOL-Teen Questionnaire.

The aim of the study was to determine the psychometric properties of the German version of the Cerebral Palsy Quality of Life Questionnaire for Children and Adolescents (CP QOL-Child and -Teen). It is a condition-specific questionnaire with a self-report version, measuring well-being rather than ill-being, which differs from existing measurement methods. Fourteen children (9-12 years) and 64 caregivers (4-12 years) answered the child questionnaire.

Decreased thalamo-cortico connectivity during an implicit sequence motor learning task and 7 days escitalopram intake.

Evidence suggests that selective serotonin reuptake inhibitors (SSRIs) reorganize neural networks via a transient window of neuroplasticity. While previous findings support an effect of SSRIs on intrinsic functional connectivity, little is known regarding the influence of SSRI-administration on connectivity during sequence motor learning. To investigate this, we administered 20 mg escitalopram or placebo for 1-week to 60 healthy female participants undergoing concurrent functional magnetic resonance imaging and sequence motor training in a double-blind randomized controlled design.

Self-Reported Medication Use and Urinary Drug Metabolites in the German Chronic Kidney Disease (GCKD) Study.

Background: Polypharmacy is common among patients with CKD, but little is known about the urinary excretion of many drugs and their metabolites among patients with CKD.

Methods: To evaluate self-reported medication use in relation to urine drug metabolite levels in a large cohort of patients with CKD, the German Chronic Kidney Disease study, we ascertained self-reported use of 158 substances and 41 medication groups, and coded active ingredients according to the Anatomical Therapeutic Chemical Classification System. We used a nontargeted mass spectrometry-based approach to quantify metabolites in urine; calculated specificity, sensitivity, and accuracy of medication use and corresponding metabolite measurements; and used multivariable regression models to evaluate associations and prescription patterns.

Phenotypic expansion of the BPTF-related neurodevelopmental disorder with dysmorphic facies and distal limb anomalies.

Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL), defined primarily by developmental delay/intellectual disability, speech delay, postnatal microcephaly, and dysmorphic features, is a syndrome resulting from heterozygous variants in the dosage-sensitive bromodomain PHD finger chromatin remodeler transcription factor BPTF gene. To date, only 11 individuals with NEDDFL due to de novo BPTF variants have been described. To expand the NEDDFL phenotypic spectrum, we describe the clinical features in 25 novel individuals with 20 distinct, clinically relevant variants in BPTF, including four individuals with inherited changes in BPTF.

Clinical effects of cardiac contractility modulation in heart failure with mildly reduced systolic function.

Aims: Increasing attention is being given to patients with heart failure and 'mid-range' left ventricular ejection fraction (LVEF, ≥40% and <50%) for whom there are no approved therapies that improve prognosis. We aim to assess for the first time the effects of cardiac contractility modulation (CCM) therapy in this patient population.

Methods And Results: We assessed the effects of 6-  month CCM therapy on functional status, exercise tolerance and quality of life in a subgroup of 53 patients with a LVEF of 40-45% recruited in previous CCM studies, including 37 patients in the CCM group and 16 in the control group.

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.