Subclonal TP53 and KRAS variants combined with poor treatment response identify ultra-high-risk pediatric T-ALL patients.

Variations in the TP53 and KRAS genes indicate a particularly adverse prognosis in relapsed pediatric T-ALL. We hypothesized that these variations might be subclonally present at disease onset and contribute to relapse risk. To test this, we examined two cohorts of children diagnosed with T-ALL: one with 81 patients who relapsed and 79 matched non-relapsing controls, and another with 226 consecutive patients, 30 of whom relapsed.

The burden of Alagille syndrome: uncovering the potential of emerging therapeutics - a comprehensive systematic literature review.

Alagille syndrome (ALGS) is a rare, cholestatic multiorgan disease associated with bile duct paucity, leading to cholestasis. Clinical symptoms of cholestasis include debilitating pruritus, xanthomas, fat-soluble vitamin deficiencies, growth failure, renal disease and impaired health-related quality of life (HRQoL). The main objective was to review the current literature on the epidemiological, clinical, psychosocial and economic burden of ALGS in view of the development of ileal bile acid transporter (IBAT) inhibitors.

Identifying genetic differences between bipolar disorder and major depression through multiple genome-wide association analyses.

Background: Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

Aims: We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

Frequency, demographics, diagnoses and consultation patterns associated with low-acuity attendances in German emergency departments: a retrospective routine healthcare data analysis from the INDEED project.

Objective: Evidence suggests interventions targeting low-acuity attendances have been hampered by insufficient characterisation of potential target groups. This study aimed to estimate the frequency of low-acuity emergency department (ED) attendances and to provide an overview of their demographic, diagnosis and consultation patterns.

Design: Observational analyses of routine healthcare data.

Predictive equation derived from 6,497 doubly labelled water measurements enables the detection of erroneous self-reported energy intake.

Nutritional epidemiology aims to link dietary exposures to chronic disease, but the instruments for evaluating dietary intake are inaccurate. One way to identify unreliable data and the sources of errors is to compare estimated intakes with the total energy expenditure (TEE). In this study, we used the International Atomic Energy Agency Doubly Labeled Water Database to derive a predictive equation for TEE using 6,497 measures of TEE in individuals aged 4 to 96 years.

Bimolecular Fluorescence Complementation (BiFC) Technique for Exocytic Proteins in Murine Hippocampal Neurons.

The bimolecular fluorescence complementation (BiFC) technique is a powerful tool for visualizing protein-protein interactions in vivo. It involves genetically fused nonfluorescent fragments of green fluorescent protein (GFP) or its variants to the target proteins of interest. When these proteins interact, the GFP fragments come together, resulting in the reconstitution of a functional fluorescent protein complex that can be observed using fluorescence microscopy.

[Quintessence of the new guidelines on physical training and fracture prophylaxis].

The guidelines on physiotherapy and exercise for osteoporosis from 2008 have recently been extensively revised on the basis of new scientific findings and possible applications. The S3 guidelines have not yet been approved by consensus and the planned completion date (Association of the Scientific Medical Societies in Germany, AWMF online, registry number 183-002) is autumn 2024. Based on the publication in Issue 3 Osteology (August 2023), key points of the guidelines on physical training and fracture prophylaxis are summarized in abridged form.

Dysregulated autoantibodies targeting AGTR1 are associated with the accumulation of COVID-19 symptoms.

Coronavirus disease 2019 (COVID-19) presents a wide spectrum of symptoms, the causes of which remain poorly understood. This study explored the associations between autoantibodies (AABs), particularly those targeting G protein-coupled receptors (GPCRs) and renin‒angiotensin system (RAS) molecules, and the clinical manifestations of COVID-19. Using a cross-sectional analysis of 244 individuals, we applied multivariate analysis of variance, principal component analysis, and multinomial regression to examine the relationships between AAB levels and key symptoms.

Evaluation of Drug-Drug Interactions in Pharmacoepidemiologic Research.

Drug-drug interactions (DDIs) represent a significant concern for clinical care and public health, but the health consequences of many DDIs remain largely underexplored. This knowledge gap underscores the critical need for pharmacoepidemiologic research to evaluate real-world health outcomes of DDIs. In this review, we summarize the definitions commonly used in pharmacoepidemiologic DDI studies, discuss common sources of bias, and illustrate through examples how these biases can be mitigated.

Long-Term Success and Survival of Post-Endodontic Restorations Without Posts After up to18 Years: A Practice-Based Study.

Objectives: The aim of this non-interventional, multi-center, prospective, practice-based study was, firstly, to evaluate the longevity of composite build-ups in endodontically treated teeth, treated with root canal therapy (ETT), without post placement and secondly, to identify and analyze factors influencing the success of these reconstructions.

Methods: Each of seven general dental practitioners placed up to 50 composite build-ups without additional posts in ETT. Teeth were restricted to incisors, canines and premolars.

Metacognitive Training for Subjects with Bipolar Disorder: A Randomized Controlled Trial.

Introduction: Impairments in social cognition in bipolar disorder (BD) have been extensively described in the last decade but few treatment strategies have been studied to address this issue. This study presents findings from a randomized controlled trial (RCT) investigating the efficacy of metacognitive training for bipolar disorder (MCT-BD) compared to Treatment as Usual (TAU) among individuals with BD in remission. The aim was to determine whether MCT-BD could improve social cognition and overall functioning in this population.

ADAMTS4-Specific MR Peptide Probe for the Assessment of Atherosclerotic Plaque Burden in a Mouse Model.

Introduction: Atherosclerosis is the underlying cause of multiple cardiovascular pathologies. The present-day clinical imaging modalities do not offer sufficient information on plaque composition or rupture risk. A disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) is a strongly upregulated proteoglycan-cleaving enzyme that is specific to cardiovascular diseases, inter alia, atherosclerosis.

Influence of Partnership Relationships on Long-Term Neurological Rehabilitation in Germany: Protocol for a Qualitative Retrospective Study.

Background: Acquired neurological diseases entail significant changes and influence the relationship between a patient and their significant other. In the context of long-term rehabilitation, those affected collaborate with health care professionals who are expected to have a positive impact on the lives of the affected individuals.

Objective: This study aims to examine the changes in the relationship between the patient and their loved ones due to acquired neurological disorders and the influence of health care professionals on this relationship.

Enhancing safety in CT-guided lung biopsies: correlation of MinIP imaging with pneumothorax risk prediction.

Objectives: This study aimed to evaluate whether minimum-intensity projection (MinIP) images could predict complications in CT-guided lung biopsies.

Methods: We retrospectively analyzed 72 procedures from January 2019 to December 2023, categorizing patients by pneumothorax and the severity of hemorrhage (grade 2 or higher). Radiodensity measurements were performed using lung window (LW) and MinIP (10-mm slab) images.

Critical reflection on the indication for computed tomography: an interdisciplinary survey of risk and benefit management in patients with sepsis.

Objectives: To survey physicians' views on the risks and benefits of computed tomography (CT) in the management of septic patients and indications for and contraindications to contrast media use in searching for septic foci.

Methods: A web-based questionnaire was administered to physicians at a large European university medical center in January 2022. A total of 371 questionnaires met the inclusion criteria and were analyzed with physicians' work experience, workplace, and medical specialty as independent variables.

Intestinal interstitial fluid isolation provides novel insight into the human host-microbiome interface.

Aims: The gastrointestinal (GI) tract is composed of distinct sub-regions, which exhibit segment-specific differences in microbial colonization and (patho)physiological characteristics. Gut microbes can be collectively considered as an active endocrine organ. Microbes produce metabolites, which can be taken up by the host and can actively communicate with the immune cells in the gut lamina propria with consequences for cardiovascular health.

Machine learning-based blood pressure estimation using impedance cardiography data.

Objective: Accurate blood pressure (BP) measurement is crucial for the diagnosis, risk assessment, treatment decision-making, and monitoring of cardiovascular diseases. Unfortunately, cuff-based BP measurements suffer from inaccuracies and discomfort. This study is the first to access the feasibility of machine learning-based BP estimation using impedance cardiography (ICG) data.

Verbal Encoding Strategies in Visuo-Spatial Working Memory.

Visual working memory and verbal storage are often investigated independently of one another. However, a growing body of evidence suggests that naming visual stimuli can provide an advantage in performance during visual working memory tasks. On the other hand, there is also evidence that labeling could lead to biases in recall.

Panitumumab plus 5-fluorouracil and folinic acid or 5-fluorouracil and folinic acid alone as maintenance therapy in RAS wild-type metastatic colorectal cancer (PanaMa, AIO KRK 0212): final efficacy analysis of a randomised, open-label, phase 2 trial.

Background: The PanaMa trial aimed to compare the efficacy of 5-fluorouracil and folinic acid (FU/FA) ± panitumumab maintenance in untreated wild-type metastatic colorectal cancer (mCRC) patients.

Methods: In this final phase 2 trial analysis, adult mCRC patients responding to six cycles of FU/FA, oxaliplatin and panitumumab were randomized (1:1, open-label) to maintenance of either FU/FA + panitumumab or FU/FA alone. The primary endpoint was superiority of progression-free survival of maintenance (PFS; time from random assignment to progression/death) in favour of FU/FA + panitumumab.

Locus coeruleus signal intensity and emotion regulation in agitation in Alzheimer's disease.

Hyperphosphorylated tau accumulation is seen in the noradrenergic locus coeruleus from the earliest stages of Alzheimer's disease onwards and has been associated with symptoms of agitation. It is hypothesized that compensatory locus coeruleus-noradrenaline system overactivity and impaired emotion regulation could underlie agitation propensity, but to our knowledge this has not previously been investigated. A better understanding of the neurobiological underpinnings of agitation would help the development of targeted prevention and treatment strategies.

Informal care for people with dementia in Europe.

Introduction: Informal care estimates for use in health-economic models are lacking. We aimed to estimate the association between informal care time and dementia symptoms across Europe.

Methods: A secondary analysis was performed on 13,529 observations in 5,369 persons from 9 European pooled cohort or trial studies in community-dwelling persons with dementia.

Endometriosis and risk of depression among oral contraceptive users: a pooled analysis of cohort studies from 13 countries.

Study Question: Does endometriosis affect the mental health of women using oral contraceptives?

Summary Answer: Among oral contraceptive users, women with endometriosis have a higher risk of depression compared to those without endometriosis, although the absolute risk increase is small.

What Is Known Already: Previous studies have suggested a potential link between endometriosis and mental health issues, but the impact of endometriosis on depression among oral contraceptive users remains unclear.

Study Design, Size, Duration: A secondary pooled cohort study utilizing data from two longitudinal patient-centric studies (INAS-VIPOS and PRO-E2) was conducted across 11 European countries, Colombia and Australia.