Fracture Prevention with Infrequent Zoledronate in Women 50 to 60 Years of Age.

Background: Zoledronate prevents fractures in older women when administered every 12 to 18 months, but its effects on bone density and bone turnover persist beyond 5 years. Whether infrequent zoledronate administration would prevent vertebral fractures in early postmenopausal women is unknown.

Methods: We conducted a 10-year, prospective, double-blind, randomized, placebo-controlled trial involving early postmenopausal women (50 to 60 years of age) with bone mineral density T scores lower than 0 and higher than -2.

Enhancing NK cell-mediated tumor killing of B7-H6 cells with bispecific antibodies targeting allosteric sites of NKp30.

In this work, we report the discovery and engineering of allosteric variable domains of the heavy chain (VHHs) derived from camelid immunization targeting NKp30, an activating receptor on natural killer (NK) cells. The aim was to enhance NK cell-mediated killing capacities by identifying VHHs that do not compete with the natural ligand of NKp30:B7-H6, thereby maximizing the recognition of B7-H6 tumor cells. By relying on the DuoBody technology, bispecific therapeutic antibodies were engineered, creating a panel of bispecific antibodies against NKp30xEGFR (cetuximab moiety) or NKp30xHER2 (trastuzumab moiety), called natural killer cell engagers (NKCEs).

The impact of highly effective modulator therapy on sinusitis and dysosmia in young children with cystic fibrosis: a prospective study protocol.

Background: Chronic rhinosinusitis (CRS) and olfactory dysfunction (OD) are prevalent disease complications in people with cystic fibrosis. These understudied comorbidities significantly impact quality of life. The impact of highly effective modulator therapy (HEMT) in young children with cystic fibrosis (YCwCF) on these disease complications is unknown.

Iron management and exercise training in individuals with chronic kidney disease: lived experiences.

Background: Non-anaemic iron deficiency is highly prevalent in people living with chronic kidney disease (CKD) but is underdiagnosed and undertreated, especially in earlier stages of CKD. A multicentre trial assessing the effect of intravenous iron supplementation in iron-deficiency but not anaemic people with CKD included a qualitative sub-study that aimed to explore the patient experience and psychosocial impact of living with CKD and iron deficiency, and the experience of the therapeutic intervention (intravenous iron and exercise).

Methods: Semi-structured interviews were conducted with 23 trial participants blinded to treatment.

A comparison of some existing and novel methods for integrating historical models to improve estimation of coefficients in logistic regression.

Model integration refers to the process of incorporating a fitted historical model into the estimation of a current study to increase statistical efficiency. Integration can be challenging when the current model includes new covariates, leading to potential model misspecification. We present and evaluate seven existing and novel model integration techniques, which employ both likelihood constraints and Bayesian informative priors.

[Functional disorders in chronic inflammatory bowel disease: the gut-brain axis].

Background: In patients with inflammatory bowel diseases (IBD), functional complaints frequently persist after the clearing of inflammation and are clinically difficult to distinguish from symptoms of inflammation. In recent years, the influence of bidirectional communication between the gut and brain on gut physiology, emotions, and behavior has been demonstrated.

Research Questions: What mechanisms underlie the development of functional gastrointestinal complaints in patients with irritable bowel syndrome (IBS) and IBD? What therapeutic approaches arise from this?

Materials And Methods: Narrative review.

ZBP1-driven cell death in severe influenza.

Influenza A virus (IAV) infections can cause life-threatening illness in humans. The severity of disease is directly linked to virus replication in the alveoli of the lower respiratory tract. In particular, the lytic death of infected alveolar epithelial cells (AECs) is a major driver of influenza severity.

Microproteins: emerging roles as antibiotics.

Recent advances in computational prediction and experimental techniques have detected previously unknown microproteins, particularly in the human microbiome. These small proteins, produced by diverse microbial species, are emerging as promising candidates for new antibiotics.

Analysis of Body Fluid Distribution, Phase Angle and Its Association With Maximal Oxygen Consumption in Facioscapulohumeral Dystrophy: An Observational Study.

Background And Aims: Body composition parameters associated with aerobic fitness, mirrored by maximal oxygen consumption (V̇Omax), have recently gained interest as indicators of physical efficiency in facioscapulohumeral dystrophy (FSHD). Bioimpedance analysis (BIA) allows a noninvasive and repeatable estimate of body composition but is based on the use of predictive equations which, if used in cohorts with different characteristics from those for which the equation was originally formulated, could give biased results. Instead, the phase angle (PhA), a BIA raw bioelectrical parameter reflecting body fluids distribution, could provide reliable data for such analysis.

Improving care experiences for premenstrual symptoms and disorders in the United Kingdom (UK): a mixed-methods approach.

Background: Poor care experiences are reported for premenstrual disorders, which may result in negative outcomes such as distress, reduced healthcare engagement, and delays to diagnosis. This research aimed to explore healthcare experiences for premenstrual symptoms in the United Kingdom and identify areas for potential improvements based on participant responses.

Method: An online survey was delivered, with participants recruited via social media.

Silica Nanoparticles: A Promising Vehicle for Anti-Cancer Drugs Delivery.

The prevalence and death due to cancer have been rising over the past few decades, and eliminating tumour cells without sacrificing healthy cells remains a difficult task. Due to the low specificity and solubility of drug molecules, patients often require high dosages to achieve the desired therapeutic effects. Silica nanoparticles (SiNPs) can effectively deliver therapeutic agents to targeted sites in the body, addressing these challenges.

Benchmarking R&D success rates of leading pharmaceutical companies: an empirical analysis of FDA approvals (2006-2022).

Previous analyses provide an industry benchmark of ∼10% for the success rate in clinical development. However, prior analyses were limited by a narrow timeframe, a diverse research focus, biases in phase-to-phase transition methodology or a focus on specific use cases. We calculated unbiased input:output ratios (Phase I to FDA new drug approval) to analyze the likelihood of first approval using data from clinicaltrials.

Impact of Sex on Clinical Outcomes of Tandem Occlusion in Acute Ischemic Stroke Patients Treated With Mechanical Thrombectomy. A Propensity-Matched Analysis.

Background: Although mechanical thrombectomy (MT) represents the standard of care for ischemic stroke due to large-vessel occlusion (LVO), the impact of sex on outcomes in tandem occlusions remains unclear. We investigated sex-based differences in outcomes after MT for tandem occlusions.

Methods: This multicenter observational study included consecutive patients with tandem occlusion treated with MT across three stroke centers (2021-2023).

Proteomic signature of HIV-associated subclinical left atrial remodeling and incident heart failure.

People living with HIV are at higher risk of heart failure and associated left atrial remodeling compared to people without HIV. Mechanisms are unclear but have been linked to inflammation and premature aging. Here we obtain plasma proteomics concurrently with cardiac magnetic resonance imaging in two independent study populations to identify parallels between HIV-related and aging-related immune dysfunction that could contribute to atrial remodeling and clinical heart failure.

Fractional flow reserve (FFR) and index of microcirculatory resistance (IMR) relationship in patients with chronic or stabilized acute coronary syndromes.

Aims: To investigate the influence of index of microcirculatory resistance (IMR) on fractional flow reserve (FFR) and adenosine-induced hyperemia (ΔPd/Pa-FFR) in patients with chronic (CCS) or stabilized acute coronary syndromes (ACS), utilizing various IMR threshold values.

Methods: Data were extracted from two ongoing Italian registries involving patients with CCS or stabilized ACS who underwent a #FullPhysiology approach [Pd/Pa, FFR, IMR, coronary flow reserve (CFR)] by bolus thermodilution technique in the left anterior descending artery. Correlations between IMR and both FFR and ΔPd/Pa-FFR were analyzed both globally and within three IMR-defined groups: Group 1 (IMR <25), Group 2 (25 ≤ IMR <40), and Group 3 (IMR ≥40).

A multilevel framework for recruitment and retention in implementation trials: An illustrative example.

Background: Implementation and hybrid effectiveness-implementation trials aspire to speed the translation of science into practice by generating crucial evidence for improving the uptake of effective health interventions. By design, they pose unique recruitment and retention challenges due to their aims, units of analysis, and sampling plans, which typically require many clinical sites (i.e.

Food Protein-Induced Allergic Proctocolitis: Real-World Experience from an Italian Cohort.

: Food protein-induced allergic proctocolitis (FPIAP) is a non-IgE-mediated food allergy, usually presenting as bloody stools in breastfed, well-appearing, and regularly growing infants. The aim of our study was to describe the clinical features of Italian infants affected by FPIAP and their management and natural history in a real-life setting. : A retrospective, observational study was performed at two tertiary pediatric hospitals (Florence and Trieste), including FPIAP-diagnosed infants between 2012 and 2022.

Differential Expression of Proteins Involved in Skin Barrier Maintenance and Vitamin D Metabolism in Atopic Dermatitis: A Cross-Sectional, Exploratory Study.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder influenced by proteins involved in skin barrier maintenance and vitamin D metabolism. Using an intra-patient design, this study compared protein expression in intra-lesional (IL) and peri-lesional (PL) skin biopsies from AD patients and examined associations between protein levels, vitamin D status, and clinical features. Forty-four biopsies from twenty-two AD patients were analyzed using antibody microarrays targeting twelve proteins.

Improving the Robustness of Deep-Learning Models in Predicting Hematoma Expansion from Admission Head CT.

Background And Purpose: Robustness against input data perturbations is essential for deploying deep-learning models in clinical practice. Adversarial attacks involve subtle, voxel-level manipulations of scans to increase deep-learning models' prediction errors. Testing deep-learning model performance on examples of adversarial images provides a measure of robustness, and including adversarial images in the training set can improve the model's robustness.

Repurposing Licensed Drugs with Activity Against Epstein-Barr Virus for Treatment of Multiple Sclerosis: A Systematic Approach.

Background: Epstein-Barr virus (EBV) is implicated as a necessary factor in the development of multiple sclerosis (MS) and may also be a driver of disease activity. Although it is not clear whether ongoing viral replication is the driver for MS pathology, MS researchers have considered the prospect of using drugs with potential efficacy against EBV in the treatment of MS. We have undertaken scientific and lived experience expert panel reviews to shortlist existing licensed therapies that could be used in later-stage clinical trials in MS.

Evaluation of efficiency and effectiveness of different recruitment strategies for the FINGER-NL multidomain lifestyle intervention trial via the Dutch Brain Research Registry.

Introduction: Recruitment of participants for intervention studies is challenging. We evaluated the effectiveness and efficiency of a participant recruitment campaign through an online registry for the FINGER-NL study, a multi-domain lifestyle intervention trial targeting cognitively healthy individuals aged 60-79 with dementia prevention potential. Additionally, we explored which recruitment strategy successfully reached individuals from underrepresented groups in research.

Pregnancy & cardiovascular disease: the PREG-CVD-HH registry.

Background: Cardiovascular disease (CVD) remains the leading cause of death in pregnant and peripartal women in western countries. Physiological changes during pregnancy can lead to cardiovascular complications in the mother; women with pre-existing heart disease may not tolerate these changes well, increasing their susceptibility to adverse cardiovascular outcomes during pregnancy. The aim of this study is to characterize pregnancy-induced changes in cardiac function, biomarker concentrations and cardiovascular outcomes in women with CVD during pregnancy at a tertiary care hospital in Germany.

Return to Work, Sport, and Sport- Related Activity After Distal Triceps Tendon Repair: A Systematic Review.

Background: Distal triceps tendon injuries are relatively rare injuries, often occurring in highly active patients with physically demanding jobs or lifestyles. Information on return to work, sport, and activity is essential for patient education and counseling after a distal triceps tendon rupture.

Purpose: To determine the rates of return to work, sport, and sport-related activity after distal triceps tendon repair.