Different niches for stem cells carrying the same oncogenic driver affect pathogenesis and therapy response in myeloproliferative neoplasms.

Aging facilitates the expansion of hematopoietic stem cells (HSCs) carrying clonal hematopoiesis-related somatic mutations and the development of myeloid malignancies, such as myeloproliferative neoplasms (MPNs). While cooperating mutations can cause transformation, it is unclear whether distinct bone marrow (BM) HSC-niches can influence the growth and therapy response of HSCs carrying the same oncogenic driver. Here we found different BM niches for HSCs in MPN subtypes.

Hospitalisations Related to Adverse Drug Reactions in Switzerland in 2012-2019: Characteristics, In-Hospital Mortality, and Spontaneous Reporting Rate.

Introduction: Adverse drug reactions (ADRs) contribute to morbidity, and serious ADRs may cause hospitalisation and death. This study characterises and quantifies ADR-related hospitalisations and subsequent in-hospital deaths, and estimates the spontaneous reporting rate to regulatory authorities in Switzerland, where healthcare professionals are legally obliged to report ADRs.

Methods: This retrospective cohort study from 2012 to 2019 analysed nationwide data from the Federal Statistical Office.

Frequency-based rare diagnoses as a novel and accessible approach for studying rare diseases in large datasets: a cross-sectional study.

Background: Up to 8% of the general population have a rare disease, however, for lack of ICD-10 codes for many rare diseases, this population cannot be generically identified in large medical datasets. We aimed to explore frequency-based rare diagnoses (FB-RDx) as a novel method exploring rare diseases by comparing characteristics and outcomes of inpatient populations with FB-RDx to those with rare diseases based on a previously published reference list.

Methods: Retrospective, cross-sectional, nationwide, multicenter study including 830,114 adult inpatients.

The Effects of Vitamin D Supplementation on Musculoskeletal Health: The VITAL and DO-Health Trials.

Previous clinical trials and systematic reviews on the effects of supplemental vitamin D on musculoskeletal outcomes are conflicting. In this paper, we review the literature and summarize the effects of a high daily dose of 2 000 IU vitamin D on musculoskeletal outcomes in generally healthy adults, in men (≥50 years) and women (≥55 years) in the 5.3-year US VITamin D and OmegA-3 TriaL (VITAL) trial (n = 25 871) and women and men (≥70 years) in the 3-year European DO-HEALTH trial (n = 2 157).

Guidance on C-reactive protein point-of-care testing and complementary strategies to improve antibiotic prescribing for adults with lower respiratory tract infections in primary care.

The world faces the threat of increasing antimicrobial resistance, and there is growing consensus that swift action must be taken to improve the rational use of antibiotics and increase the stewardship of antibiotics to safeguard this key resource in modern healthcare. This paper provides the perspective of an international group of experts on the role of C-reactive protein point-of-care testing (CRP POCT) and other complementary strategies to improve antibiotic stewardship in primary care, with regards to the diagnosis and treatment of adult patients presenting symptoms of lower respiratory tract infections (LRTIs). It provides guidance regarding the clinical assessment of symptoms in combination with C-reactive protein (CRP) results, at the point of care, to support the management decision, and discusses enhanced patient communication and delayed prescribing as complementary strategies to decrease the inappropriate use of antibiotics.

Mortality and morbidity related to hepatitis C virus infection in hospitalized adults-A propensity score matched analysis.

The World Health Organization (WHO) aims to reduce HCV mortality, but estimates are difficult to obtain. We aimed to identify electronic health records of individuals with HCV infection, and assess mortality and morbidity. We applied electronic phenotyping strategies on routinely collected data from patients hospitalized at a tertiary referral hospital in Switzerland between 2009 and 2017.

The Impact of COVID-19 on Mental Healthcare Utilization in Switzerland Was Strongest Among Young Females-Retrospective Study in 2018-2020.

To provide a thorough assessment of the impact of the COVID-19 pandemic on the utilization of inpatient and outpatient mental healthcare in Switzerland. Retrospective cohort study using nationwide hospital data ( > 8 million) and claims data from a large Swiss health insurer ( > 1 million) in 2018-2020. Incidence proportions of different types of psychiatric inpatient admissions, psychiatric consultations, and psychotropic medication claims were analyzed using interrupted time series models for the general population and for the vulnerable subgroup of young people.

Adolescents' self-reported health status, behaviours and health issues addressed during routine school doctor consultations in Switzerland: an observational study.

Background: We aimed to investigate the self-reported health status and behaviours of 7th-grade adolescents, associations with gender and educational track, as well as health issues addressed during routine school doctor consultations in Switzerland.

Methods: Data on health status and behaviours, specifically general well-being, stimulant and addictive substance use, bullying/violence, exercise, nutrition and health protection, and puberty/sexuality, were drawn from routinely collected self-assessment questionnaires from 1076 (of a total of 1126) students from 14 schools in the Swiss canton of Zug in 2020. Data on health issues addressed in school doctor consultations were collected by nine school doctors (for 595 individual consultations).

Optimising prescribing in older adults with multimorbidity and polypharmacy in primary care (OPTICA): cluster randomised clinical trial.

Objective: To study the effects of a primary care medication review intervention centred around an electronic clinical decision support system (eCDSS) on appropriateness of medication and the number of prescribing omissions in older adults with multimorbidity and polypharmacy compared with a discussion about medication in line with usual care.

Design: Cluster randomised clinical trial.

Setting: Swiss primary care, between December 2018 and February 2021.

Growth differentiation factor-15 and prediction of cancer-associated thrombosis and mortality: a prospective cohort study.

Background: Patients with cancer are at increased risk of venous thromboembolism (VTE) and arterial thromboembolic/thrombotic events (ATEs). Growth differentiation factor-15 (GDF-15) improves cardiovascular risk assessment, but its predictive utility in patients with cancer remains undefined.

Objectives: To investigate the association of GDF-15 with the risks of VTE, ATE, and mortality in patients with cancer and its predictive utility alongside established models.

Patient Blood Management in Liver Transplant-A Concise Review.

Transfusion of blood products in orthotopic liver transplantation (OLT) significantly increases post-transplant morbidity and mortality and is associated with reduced graft survival. Based on these results, an active effort to prevent and minimize blood transfusion is required. Patient blood management is a revolutionary approach defined as a patient-centered, systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient's own blood while promoting patient safety and empowerment.

Apoptotic cell death in disease-Current understanding of the NCCD 2023.

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions.

Blocking the CD47-SIRPα interaction reverses the disease phenotype in a polycythemia vera mouse model.

Polycythemia vera (PV) is a hematopoietic stem cell neoplasm driven by somatic mutations in JAK2, leading to increased red blood cell (RBC) production uncoupled from mechanisms that regulate physiological erythropoiesis. At steady-state, bone marrow macrophages promote erythroid maturation, whereas splenic macrophages phagocytose aged or damaged RBCs. The binding of the anti-phagocytic ("don't eat me") CD47 ligand expressed on RBCs to the SIRPα receptor on macrophages inhibits phagocytic activity protecting RBCs from phagocytosis.

Targeting of epigenetic co-dependencies enhances anti-AML efficacy of Menin inhibitor in AML with MLL1-r or mutant NPM1.

Monotherapy with Menin inhibitor (MI), e.g., SNDX-5613, induces clinical remissions in patients with relapsed/refractory AML harboring MLL1-r or mtNPM1, but most patients either fail to respond or eventually relapse.

Avatar-based patient monitoring improves information transfer, diagnostic confidence and reduces perceived workload in intensive care units: computer-based, multicentre comparison study.

Patient monitoring is the foundation of intensive care medicine. High workload and information overload can impair situation awareness of staff, thus leading to loss of important information about patients' conditions. To facilitate mental processing of patient monitoring data, we developed the Visual-Patient-avatar Intensive Care Unit (ICU), a virtual patient model animated from vital signs and patient installation data.

Altered Distribution of Unesterified Cholesterol among Lipoprotein Subfractions of Patients with Diabetes Mellitus Type 2.

Biomarkers are important tools to improve the early detection of patients at high risk for developing diabetes as well as the stratification of diabetic patients towards risks of complications. In addition to clinical variables, we analyzed 155 metabolic parameters in plasma samples of 51 healthy volunteers and 66 patients with diabetes using nuclear magnetic resonance (NMR) spectrometry. Upon elastic net analysis with lasso regression, we confirmed the independent associations of diabetes with branched-chain amino acids and lactate (both positive) as well as linoleic acid in plasma and HDL diameter (both inverse).

Hypoxia-altitude simulation test to predict altitude-related adverse health effects in COPD patients.

Background/aims: Amongst numerous travellers to high altitude (HA) are many with the highly prevalent COPD, who are at particular risk for altitude-related adverse health effects (ARAHE). We then investigated the hypoxia-altitude simulation test (HAST) to predict ARAHE in COPD patients travelling to altitude.

Methods: This prospective diagnostic accuracy study included 75 COPD patients: 40 women, age 58±9 years, forced expiratory volume in 1 s (FEV) 40-80% pred, oxygen saturation measured by pulse oximetry ( ) ≥92% and arterial carbon dioxide tension ( ) <6 kPa.

Oxygen Therapy in Pulmonary Vascular Disease: A Systematic Review, Meta-Analysis, and Comment.

Main pulmonary vascular diseases (PVD) with precapillary pulmonary hypertension (PH) are pulmonary arterial and chronic thromboembolic PH. Guidelines recommend supplemental oxygen therapy (SOT) for severely hypoxemic patients with PH, but evidence is scarce. The authors performed a systematic review and where possible meta-analyses on the effects of SOT on hemodynamics and exercise performance in patients with PVD.

Substances from unregulated drug markets - A retrospective data analysis of customer-provided samples from a decade of drug checking service in Zurich (Switzerland).

Background: Drug checking services (DCS) are harm reduction interventions for people who consume illicit substances. Unregulated drug markets lead to samples with unexpected and variable contents. A retrospective data analysis of Zurich's DCS was performed to determine the nature of these samples.

Impact of low-grade intraventricular hemorrhage on neurodevelopmental outcome in very preterm infants at two years of age.

Background: High-grade intraventricular hemorrhage (IVH) in very preterm infants is a known risk factor for adverse neurodevelopmental outcome. Prognosis is less clear for low-grade (grades I/II) IVH however, with conflicting study results in recent years.

Objective: To evaluate the impact of low-grade IVH on neurodevelopmental outcome at 2 years corrected age in preterm infants born below 32 weeks gestation at the University hospital of Zurich between 2009 and 2014.