A phase 1b/2 study evaluating efficacy and safety of MP0250, a designed ankyrin repeat protein (DARPin) simultaneously targeting vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), in combination with bortezomib and dexamethasone, in patients with relapsed or refractory multiple myeloma.

MP0250 is a designed ankyrin repeat protein that specifically inhibits both vascular endothelial growth factor A (VEGF-A) and hepatocyte growth factor (HGF), aiming at potentiating cancer therapy by disrupting the tumour microenvironment. Encouraging results from a phase 1 trial of MP0250 in patients with solid tumours prompted further investigation in multiple myeloma (MM) as both MP0250 targets are reported to be drivers of MM pathogenesis. In this open-label, single-arm phase 1b/2 study (NCT03136653) in patients with proteasome inhibitor- and/or immunomodulatory drug-relapsed or refractory MM, MP0250 was administered every 3 weeks with standard bortezomib/dexamethasone regimen.

Protecting the health of the most vulnerable in the overlooked Democratic Republic of Congo crisis.

Background And Aim: The Democratic Republic of Congo (DRC) is facing a humanitarian crisis due to prolonged conflicts, human rights abuses, and gender-based violence. This perspective article aims to discuss the challenges faced by vulnerable populations in the DRC, including the impact of interventions and broader humanitarian strategies.

Methods: A search on Google Scholar was carried out to identify relevant journal articles.

Recognition, diagnosis, and operability assessment of chronic thromboembolic pulmonary hypertension (CTEPH): A global cross-sectional scientific survey (CLARITY).

Early recognition and diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is crucial for improving prognosis and reducing the disease burden. Established clinical practice guidelines describe interventions for the diagnosis and evaluation of CTEPH, yet limited insight remains into clinical practice variation and barriers to care. The CTEPH global cross-sectional scientific survey (CLARITY) was developed to gather insights into the current diagnosis, treatment, and management of CTEPH and to identify unmet medical needs.

Exercise Training Decreases Nitrite Concentration in the Heart and Locomotory Muscles of Rats Without Changing the Muscle Nitrate Content.

Background: Skeletal muscles are postulated to be a potent regulator of systemic nitric oxide homeostasis. In this study, we aimed to evaluate the impact of physical training on the heart and skeletal muscle nitric oxide bioavailability (judged on the basis of intramuscular nitrite and nitrate) in rats.

Methods And Results: Rats were trained on a treadmill for 8 weeks, performing mainly endurance running sessions with some sprinting runs.

A challenging diagnosis of idiopathic multicentric Castleman disease with complex systemic presentation: A case report.

Key Clinical Message: Idiopathic multicentric Castleman disease (iMCD) is challenging to diagnose due to clinical similarities with other conditions, such as Still's disease. Once diagnosed, iMCD may be effectively managed with the anti-interleukin-6 antibody siltuximab.

Abstract: Here, we present the case of a 19-year-old Polish woman with persistent fever and enlarged lymph nodes and whose diagnosis remained inconclusive following initial clinical assessments and extensive laboratory analyses.

Strengthening rural surgery in the Philippines: Essential in achieving universal health care.

The Lancet Commission on Global Surgery (LCoGS) launched Global Surgery 2030 to address the surgical services inequities with a bias toward low-income and middle-income countries like the Philippines. The same inequity is observed particularly when it comes to the urban-rural divide. With more than half of the population living in rural areas, access to surgery becomes a major challenge that further impedes the much-needed health of an economically productive workforce.

Machine learning in the diagnosis of asthma phenotypes during coronavirus disease 2019 pandemic.

Background: During the coronavirus disease 2019 (COVID-19) pandemic, it has become a pressing need to be able to diagnose aspirin hypersensitivity in patients with asthma without the need to use oral aspirin challenge (OAC) testing. OAC is time consuming and is associated with the risk of severe hypersensitive reactions. In this study, we sought to investigate whether machine learning (ML) based on some clinical and laboratory procedures performed during the pandemic might be used for discriminating between patients with aspirin hypersensitivity and those with aspirin-tolerant asthma.

Pru du 1, the Bet 1-homologue from almond, is a major allergen in patients with birch pollen associated almond allergy.

Background: Almond allergy is common and can manifest in two different forms. Primary almond allergy has been reported to be associated with sensitization to almond legumin Pru du 6. In birchendemic regions, there is a link between birch-pollinosis which is likely based on a cross-reactive Bet v 1 homologue, a yet unidentified allergen in almond.

Contact allergens in moisturizers in preventative emollient therapy - A systematic review.

Background: Results of preventative emollient therapy on atopic dermatitis and food allergy trials are inconsistent. In addition to the ingredients considered beneficial, the moisturizers may contain potentially harmful haptens. This study aimed to assess the prevalence of haptens in moisturizers used in studies to prevent atopic dermatitis or food allergy and assess their correlations to the trial results.

Comparison of six risk scores for the prediction of atrial fibrillation recurrence after cryoballoon-based ablation and development of a simplified method, the 0-1-2 PL score.

Introduction: There are several prognostic scores for the assessment of risk of atrial fibrillation (AF) recurrence post ablation procedure. However, the use of these complex scores is difficult and the validation on different populations brought divergent results. Our goal was to compare the performance of these risk scores as the basis for the development of a new, simplified score based only on few universally predictive variables.

Illustrated State-of-the-Art Capsules of the ISTH 2020 Congress.

This year's Congress of the International Society of Thrombosis and Haemostasis (ISTH) was hosted virtually from Philadelphia July 17-21, 2021. The conference, now held annually, highlighted cutting-edge advances in basic, population and clinical sciences of relevance to the Society. Despite being held virtually, the 2021 congress was of the same scope and quality as an annual meeting held in person.

In Vivo Magnetic Resonance Imaging-Based Detection of Heterogeneous Endothelial Response in Thoracic and Abdominal Aorta to Short-Term High-Fat Diet Ascribed to Differences in Perivascular Adipose Tissue in Mice.

Background Long-term feeding with a high-fat diet (HFD) induces endothelial dysfunction in mice, but early HFD-induced effects on endothelium have not been well characterized. Methods and Results Using an magnetic resonance imaging-based methodology that allows characterization of endothelial function in vivo, we demonstrated that short-term (2 weeks) feeding with a HFD to mice or to mice resulted in the impairment of acetylcholine-induced response in the abdominal aorta (AA), whereas, in the thoracic aorta (TA), the acetylcholine-induced response was largely preserved. Similarly, HFD resulted in arterial stiffness in the AA, but not in the TA.

Identification of Key Small Non-Coding MicroRNAs Controlling Pacemaker Mechanisms in the Human Sinus Node.

Background The sinus node (SN) is the primary pacemaker of the heart. SN myocytes possess distinctive action potential morphology with spontaneous diastolic depolarization because of a unique expression of ion channels and Ca-handling proteins. MicroRNAs (miRs) inhibit gene expression.

Combined Influence of Waist and Hip Circumference on Risk of Death in a Large Cohort of European and Australian Adults.

Background Waist circumference and hip circumference are both strongly associated with risk of death; however, their joint association has rarely been investigated. Methods and Results The MONICA Risk, Genetics, Archiving, and Monograph (MORGAM) Project was conducted in 30 cohorts from 11 countries; 90 487 men and women, aged 30 to 74 years, predominantly white, with no history of cardiovascular disease, were recruited in 1986 to 2010 and followed up for up to 24 years. Hazard ratios were estimated using sex-specific Cox models, stratified by cohort, with age as the time scale.

Age-Dependent Impairment in Endothelial Function and Arterial Stiffness in Former High Class Male Athletes Is No Different to That in Men With No History of Physical Training.

Background Physical activity is generally considered to exert positive effects on the cardiovascular system in humans. However, surprisingly little is known about the delayed effect of professional physical training performed at a young age on endothelial function and arterial stiffness in aging athletes. The present study aimed to assess the impact of long-lasting professional physical training (endurance and sprint) performed at a young age on the endothelial function and arterial stiffness reported in older age in relation to glycocalyx injury, prostacyclin and nitric oxide production, inflammation, basal blood lipid profile, and glucose homeostasis.

Influence of anticardiolipin and anti-β2 glycoprotein I antibody cutoff values on antiphospholipid syndrome classification.

Background: Anticardiolipin (aCL) and anti-β2 glycoprotein I (aβ2GPI) immunoglobulin (Ig) G/IgM antibodies are 2 of the 3 laboratory criteria for classification of antiphospholipid syndrome (APS). The threshold for clinically relevant levels of antiphospholipid antibodies (aPL) for the diagnosis of APS remains a matter of debate. The aim of this study was to evaluate the variation in cutoffs as determined in different clinical laboratories based on the results of a questionnaire as well as to determine the optimal method for cutoff establishment based on a clinical approach.

Defects of splicing in antithrombin deficiency.

Background: There is increasing evidence supporting the relevance of aberrant splicing in multiple disorders. In antithrombin deficiency only 22 intronic mutations affecting splicing sites (7% of mutations) are considered as splicing mutations.

Methods: was analyzed by Sanger sequencing and MLPA in 141 unrelated cases with antithrombin deficiency.

Temporary external implantable cardioverter-defibrillator as a bridge to reimplantation after infected device extraction.

Patients with cardiac implantable electronic devices (CIED) and endovascular infection represent a difficult management group. The explantation of an implantable cardioverter-defibrillator (ICD) system deprives the patient of the protection against life-threatening ventricular tachyarrhythmias. In this study, we describe feasibility and clinical outcomes of bridging with temporary dual-coil ICD lead and external ICD following the extraction of a CIED due to endovascular infection and compare the performance of this approach to other available options.

Factors associated with skeletal muscle mass, sarcopenia, and sarcopenic obesity in older adults: a multi-continent study.

Background: The aim of this study was to evaluate the factors associated with low skeletal muscle mass (SMM), sarcopenia, and sarcopenic obesity using nationally representative samples of people aged ≥65 years from diverse geographical regions of the world.

Methods: Data were available for 18 363 people aged ≥65 years who participated in the Collaborative Research on Ageing in Europe survey conducted in Finland, Poland, and Spain, and the World Health Organization Study on global AGEing and adult health survey conducted in China, Ghana, India, Mexico, Russia, and South Africa, between 2007 and 2012. A skeletal muscle mass index (SMI) was created to reflect SMM.

Number of circulating pro-angiogenic cells, growth factor and anti-oxidative gene profiles might be altered in type 2 diabetes with and without diabetic foot syndrome.

Aims/introduction: Type 2 diabetes is often complicated by diabetic foot syndrome (DFS). We analyzed the circulating stem cells, growth factor and anti-oxidant gene expression profiles in type 2 diabetes patients without or with different forms of DFS.

Materials And Methods: Healthy volunteers (n = 13) and type 2 diabetes patients: (i) without DFS (n = 10); or with (ii) Charcot osteoneuropathy (n = 10); (iii) non-infected (n = 17); (iv) infected (n = 11); and (v) healed ulceration were examined (n = 12).