Serially quantifying TERT rearrangement breakpoints in circulating tumor DNA enables minimal residual disease monitoring in patients with neuroblastoma.

Telomerase is reactivated by genomic TERT rearrangements in ~30% of diagnosed high-risk neuroblastomas. Dismal patient prognosis results if the RAS/MAPK/ALK signaling transduction network also harbors mutations. We present a liquid biopsy-based monitoring strategy for this particularly vulnerable pediatric patient subgroup, for whom real-time molecular diagnostic tools are limited to date.

Acral melanoma of the heel mimicking a pressure sore.

Background: The clinical appearance of acral melanoma is diverse and can cause diagnostic difficulties in individual cases.

Case Description: We present a clinical case of an 83-year-old patient with a melanoma in the heel area that was initially interpreted as a pressure ulcer, resulting in delayed and more complicated treatment.

Conclusions: Melanomas should be included in the differential diagnosis even in "typical" pressure ulcer areas.

Ovarian cancer management in an ESGO ovarian cancer center of excellence: a systematic case study of the interprofessional and interdisciplinary interaction.

Purpose: With growing knowledge about ovarian cancer over the last decades, diagnosis, evaluation and treatment of ovarian cancer patients have become highly specialized, and an individually adapted approach should be made in each woman by interdisciplinary cooperation. The present study aims to show the variety and extent of medical specialties involved at our institution according to the European Society of Gynecologic Oncology (ESGO) Quality indicators (QI).

Methods: A woman, diagnosed with high-grade ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) class IVb was selected for a single case observational study.

Molecular determinants of clinical outcomes of pembrolizumab in recurrent ovarian cancer: Exploratory analysis of KEYNOTE-100.

Objective: This prespecified exploratory analysis evaluated the association of gene expression signatures, tumor mutational burden (TMB), and multiplex immunohistochemistry (mIHC) tumor microenvironment-associated cell phenotypes with clinical outcomes of pembrolizumab in advanced recurrent ovarian cancer (ROC) from the phase II KEYNOTE-100 study.

Methods: Pembrolizumab-treated patients with evaluable RNA-sequencing (n = 317), whole exome sequencing (n = 293), or select mIHC (n = 125) data were evaluated. The association between outcomes (objective response rate [ORR], progression-free survival [PFS], and overall survival [OS]) and gene expression signatures (T-cell-inflamed gene expression profile [TcellGEP] and 10 non-TcellGEP signatures), TMB, and prespecified mIHC cell phenotype densities as continuous variables was evaluated using logistic (ORR) and Cox proportional hazards regression (PFS; OS).

New minimally-invasive approach in adult for Chiari I malformation.

Background: Chiari I malformation is defined by tonsillar herniation through the foramen magnum. There is no consensus on the treatment of Chiari malformation. A simple follow-up is recommended for asymptomatic cases.

Overall survival and patient-reported outcome results from the placebo-controlled randomized phase III IMagyn050/GOG 3015/ENGOT-OV39 trial of atezolizumab for newly diagnosed stage III/IV ovarian cancer.

Objective: To determine the impact on overall survival (OS) and patient-reported outcomes (PROs) of combining atezolizumab with standard therapy for newly diagnosed stage III/IV ovarian cancer.

Methods: The placebo-controlled double-blind randomized phase III IMagyn050/GOG 3015/ENGOT-OV39 trial (NCT03038100) assigned eligible patients to 3-weekly atezolizumab 1200 mg or placebo for 22 cycles with platinum-based chemotherapy and bevacizumab. Coprimary endpoints were progression-free survival (already reported) and OS in the PD-L1-positive and intent-to-treat (ITT) populations, tested hierarchically.

Molecular Results and Potential Biomarkers Identified from the Phase 3 MILO/ENGOT-ov11 Study of Binimetinib versus Physician Choice of Chemotherapy in Recurrent Low-Grade Serous Ovarian Cancer.

Purpose: We present the results of a post hoc tumor tissue analysis from the phase 3 MILO/ENGOT-ov11 study (NCT01849874).

Patients And Methods: Mutation/copy-number analysis was performed on tissue obtained pre-randomization. The Kaplan-Meier method was used to estimate progression-free survival (PFS).

Therapeutic Reference Range for Olanzapine in Schizophrenia: Systematic Review on Blood Concentrations, Clinical Effects, and Dopamine Receptor Occupancy.

Aiming at revising the therapeutic reference range for olanzapine, the present study highlights the association between blood olanzapine levels, clinical effects, and dopamine D-receptor occupancy for oral and long-acting injectable (LAI) formulations. Databases were systematically searched for randomized controlled trials (RCTs) and uncontrolled trials concerning blood olanzapine levels in relation to clinical outcomes or D-receptor occupancy using MEDLINE (PubMed), Web of Science, PsycINFO, and Cochrane Library (March 2021, updated in December 2021). We excluded articles not written in English or German and non-human data.

The oxygen dissociation curve of blood in COVID-19-An update.

An impressive effect of the infection with SARS-Co-19 is the impairment of oxygen uptake due to lung injury. The reduced oxygen diffusion may potentially be counteracted by an increase in oxygen affinity of hemoglobin. However, hypoxia and anemia associated with COVID-19 usually decrease oxygen affinity due to a rise in [2,3-bisphosphoglycerate].

Chronic Spontaneous Urticaria: The Role and Relevance of Autoreactivity, Autoimmunity, and Autoallergy.

Chronic spontaneous urticaria (CSU) is a frequent and often severely disabling disease. A large number of studies were performed during the last 2 decades to clarify its pathogenesis. These studies shed light on the underlying autoimmune mechanisms of CSU pathogenesis and have led us to understand that different mechanisms may exist and, sometimes, coexist behind the same clinical presentation.

A comparison between different suture techniques in lumbar spine surgery.

As a result of solicited muscles, strong friction, and tensile force on cutaneous tissue, the difference in closure procedure and management strategies and complications of surgical incision healing is a real challenge in lumbar spine surgery. We performed a retrospective study to compare different types of wound closure in lumbar spine surgery. 4383 patients were included in this study.

PDGFRβ promotes oncogenic progression via STAT3/STAT5 hyperactivation in anaplastic large cell lymphoma.

Background: Anaplastic large cell lymphoma (ALCL) is an aggressive non-Hodgkin T cell lymphoma commonly driven by NPM-ALK. AP-1 transcription factors, cJUN and JUNb, act as downstream effectors of NPM-ALK and transcriptionally regulate PDGFRβ. Blocking PDGFRβ kinase activity with imatinib effectively reduces tumor burden and prolongs survival, although the downstream molecular mechanisms remain elusive.

Diverse pharmacological properties, trial results, comorbidity prescribing and neural pathophysiology suggest European hypertension guideline downgrading of beta-blockers is not justified.

Beta-blockers have solid documentation in preventing cardiovascular complications in the treatment of hypertension; atenolol, metoprolol, oxprenolol and propranolol demonstrate proven cardiovascular prevention in hypertension mega-trials. Hypertension is characterised by activation of the sympathetic nervous system from early to late phases, which makes beta-blockers an appropriate treatment seen from a pathophysiological viewpoint, especially in patients with an elevated heart rate. Beta-blockers represent a heterogenous class of drugs with regard to both pharmacodynamic and pharmacokinetic properties.

Remote Patient Management May Reduce All-Cause Mortality in Patients With Heart-Failure and Renal Impairment.

Background: Remote patient management (RPM) in heart failure (HF) patients has been investigated in several prospective randomized trials. The Telemedical Interventional Management in Heart Failure II (TIM-HF2)-trial showed reduced all-cause mortality and hospitalizations in heart failure (HF) patients using remote patient management (RPM) vs. usual care (UC).

Comment on Ceruti et al. Temporal Changes in the Oxyhemoglobin Dissociation Curve of Critically Ill COVID-19 Patients. 2022, , 788.

Ceruti et al. describe in their article very low standard half saturation pressures (P) in COVID-19 patients, calculated with the Dash et al. equations.

Cerebrovascular Events in Suspected Sepsis: Retrospective Prevalence Study in Critically Ill Patients Undergoing Full-Body Computed Tomography.

Purpose: This study aimed at retrospectively evaluating full-body computed tomography (CT) examinations for the prevalence of cerebrovascular events in patients with suspected sepsis treated in the intensive care unit (ICU).

Methods: All full-body CT examinations, i.e.

Guideline Adherence of Paediatric Urolithiasis: An EAU Members' Survey and Expert Panel Roundtable Discussion.

Background: Paediatric nephrolithiasis has increased globally, requiring standardized recommendations. This study aims to assess the paediatric urolithiasis care between EAU members along with the statements of three experts in this field. Methods: The results of an electronic survey among EAU members comparing the guideline recommendations to their current practice managing paediatric nephrolithiasis in 74 centres are contrasted with insights from an expert-panel.