Escalation

PURPOSE: Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate consisting of a humanized antitrophoblast cell-surface antigen 2 (TROP2) monoclonal antibody linked to a potent, exatecan-derived topoisomerase I inhibitor payload via a plasma-stable, selectively cleavable linker. PATIENTS AND METHODS: TROPION-PanTumor01 (ClinicalTrials.gov identifier: NCT03401385) is a phase I, dose-escalation, and dose-expansion study evaluating Dato-DXd in patients with previously treated solid tumors...

PURPOSE: This phase 1 trial aimed to determine the maximum tolerated fraction dose (MTFD) of hypofractionated radiotherapy (hypo-RT) combined with concurrent chemotherapy and subsequent consolidation immune checkpoint inhibitors (cICI) for patients with locally advanced non-small cell lung cancer (LA-NSCLC). PATIENTS AND METHODS: Split-course hypo-RT and hypo-boost combined with concurrent chemotherapy were administered at three dose levels (DLs), using a stepwise dose-escalation protocol...

ConspectusIn the ever-increasing renewable-energy demand scenario, developing new photovoltaic technologies is important, even in the presence of established terawatt-scale silicon technology. Emerging photovoltaic technologies play a crucial role in diversifying material flows while expanding the photovoltaic product portfolio, thus enhancing security and competitiveness within the solar industry. They also serve as a valuable backup for silicon photovoltaic, providing resilience to the overall energy infrastructure...

PURPOSE OF THE REVIEW: Antiphospholipid syndrome (APS) is a rare systemic autoimmune disorder that can escalate into a 'thrombotic storm' called the catastrophic antiphospholipid syndrome (CAPS), frequently requiring ICU admission for multiple organ failure. This review aims to offer insight and recent evidence on critically-ill APS patients. RECENT FINDINGS: The CAPS classification criteria define this condition as the involvement of at least three organs/systems/tissues within less than a week, caused by small vessel thrombosis, in patients with elevated antiphospholipid antibodies levels...

PURPOSE: ARO-HIF2 is an siRNA drug designed to selectively target hypoxia-inducible factor-2α (HIF2α) interrupting downstream pro-oncogenic signaling in clear cell renal cell carcinoma (ccRCC). The aims of this Phase 1 study (AROHIF21001) were to evaluate safety, tolerability, pharmacokinetics, and establish a recommended Phase 2 dose. PATIENTS AND METHODS: Subjects with ccRCC and progressive disease after at least 2 prior therapies that included VEGF and immune checkpoint inhibitors were progressively enrolled into dose-escalation cohorts of ARO-HIF2 administered intravenously at 225, 525, or 1,050 mg weekly...

BACKGROUND: Left ventricular assist devices (LVAD) improve survival for patients with cardiac failure, but LVAD specific infections (VSI) remain a challenge with poorly understood predictive risk factors. Furthermore, the indications and utility of escalating medical treatment to surgical debridement and potential flap reconstruction are not well-characterized. STUDY DESIGN: A retrospective review of consecutive patients undergoing primary LVAD implantation at a tertiary academic center was performed...

In response to the escalating demand for sustainable agricultural methodologies, the utilization of microbial volatile organic compounds (VOCs) as antagonists against phytopathogens has emerged as a viable eco-friendly alternative. Microbial volatiles exhibit rapid diffusion rates, facilitating prompt chemical interactions. Moreover, microorganisms possess the capacity to emit volatiles constitutively, as well as in response to biological interactions and environmental stimuli. In addition to volatile compounds, these bacteria demonstrate the ability to produce soluble metabolites with antifungal properties, such as APE Vf, pyoverdin, and fragin...

Background: The imminent increase in overweight and obesity prevalence constitutes a pervasive concern for the adult and pediatric Colombian population. Nonetheless, the unequal distribution across distinct social groups limits the implementation of public health policies targeting these escalating rates. Aim: This study aimed to compile existing evidence regarding the prevalence of overweight and obesity in relation to the socioeconomic status (SES) of the Colombian population. Methods: A scoping review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews parameters in MEDLINE (PubMed), EMBASE, and LILACS databases for inclusion of investigations published up to January 2024...

Preparing enrolled nurses (ENs) to effectively work with mental health consumers is crucial to meeting Australia's healthcare demands. This qualitative study aimed to explore various stakeholders' perceptions regarding the mental health knowledge, skills, and attributes (KSAs) required by ENs to engage with individuals experiencing mental health issues, thus guiding future training priorities. The sample comprised 44 participants including 18 students, 3 graduate ENs, 5 experienced ENs, 5 registered nurses (RNs), 4 nurse unit managers (NUMs), 5 teachers, and 5 consumers of mental health services...

BACKGROUND: Retifanlimab is a humanized monoclonal antibody targeting programmed death protein-1, and INCB001158 is an oral arginase inhibitor. This phase Ib study investigated retifanlimab, INCB001158, and their combination in Japanese patients with advanced solid tumors. METHODS: Patients received retifanlimab (500 mg every 4 weeks [Q4W] i.v.) or escalating doses of INCB001158 (75 or 100 mg twice daily [BID]) monotherapy in Part 1 and combination of retifanlimab (500 mg Q4W) and INCB001158 (100 mg BID) in Part 2...

INTRODUCTION: Human papillomavirus Virus (HPV)-associated oropharyngeal squamous cell carcinoma (OSCC) has increased in incidence in recent decades and represents a heterogeneous disease entity in the context of Head and Neck Squamous Cell Carcinoma (HNSCC), in terms of disease prognosis. Treatment of locoregionally advanced OSCC is mainly based on concurrent chemoradiotherapy. Given the younger age of patients, if compared with HPV-negative counterparts, and the high cure rates, the acute- and long-term toxicity in survivors represents a field of interest...

Human ageing, along with the ageing of conventional model organisms, is depicted as a continuous and progressive decline of biological capabilities accompanied by an exponentially increasing mortality risk. However, not all organisms experience ageing identically and our understanding of the phenomenon is coloured by human-centric views. Ageing is multifaceted and influences a diverse range of species in varying ways. Some undergo swift declines post-reproduction, while others exhibit insubstantial changes throughout their existence...

An exploratory mixed methods design was used to explore age-appropriate characteristics of parental response to emotion (PRE) during adolescence in Chinese families and develop the parental response to adolescents' emotions scale (C-PRAES). Qualitative interviews with 21 parent-adolescent dyads were employed to explore characteristics of PRE in adolescence and generate item pools. Structural validity, criterion validity, measurement invariance across informants (adolescents vs. parents, mothers vs. fathers) and consistency reliability were examined in the quantitative phase (Nadolescent  = 702, Nparent  = 476)...

AIM: (1) To assess the release of stable silver nanoparticles (AgNPs) of small scale dimension added to heat polymerized polymethyl methacrylate (PMMA) in 6 months. (2) Assessing the influence of incorporating minimal concentrations of stable AgNPs with nanoscale dimensions into heat polymerized PMMA over a 6 month period on its antifungal efficacy (AF), flexural strength (FS), and impact strength (IS). SETTINGS AND DESIGN: Incorporating nanoparticles with a very small scale may have minimal impact on mechanical properties due to their diminutive size...

The escalating costs of healthcare services and a growing awareness of personal health responsibilities have led individuals to explore natural methods alongside conventional medicines for health improvement and disease prevention. The aging global population is experiencing increased health needs, notably related to conditions like diabetes, heart disease, and hypertension. Lifestyle-related diseases, poor dietary habits, and sedentary lifestyles underscore the importance of foods containing nutrients that can aid in preventing and managing these diseases...

Polygenic variation unrelated to disease contributes to interindividual variation in baseline white blood cell (WBC) counts, but its clinical significance is uncharacterized. We investigated the clinical consequences of a genetic predisposition toward lower WBC counts among 89,559 biobank participants from tertiary care centers using a polygenic score for WBC count (PGSWBC ) comprising single nucleotide polymorphisms not associated with disease. A predisposition to lower WBC counts was associated with a decreased risk of identifying pathology on a bone marrow biopsy performed for a low WBC count (odds-ratio = 0...

Circulating tumor DNA (ctDNA) consists of DNA fragments released from cancer cells into the blood circulation with quick clearance. Analysis of ctDNA can enable real-time assessment of the presence of cancer cells and their genomic characteristics. Therefore, ctDNA is expected to be one of the most useful biomarkers for cancer. In recent years, several ultra-sensitive assays for ctDNA analysis have been developed, and many clinical trials are using these assays to investigate the efficacy of ctDNA-based therapeutic strategies...

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This review addresses the escalating challenge posed by antibiotic resistance, highlighting its profound impact on global public health, including increased mortality rates and healthcare expenditures. The review focuses on the need to adopt the One Health approach to effectively manage antibiotic usage across human, animal, and environmental domains. Antimicrobial stewardship programs (ASPs) are considered as comprehensive strategies that encompass both core and supplementary initiatives aimed at enhancing prudent antibiotic use...

The collapse of the Soviet Union triggered an escalation of the tuberculosis (TB) epidemic in many post-Soviet countries, including Ukraine. The main reasons for this situation include both the approach to TB care and the concentration of TB cases in prisons. The neoliberal approach to TB care system reform promises the optimization of treatment terms, "dehospitalization" and "despecialization" of the system of care, and a different type of control, established through digital technologies. One such technology is the "e-TB Manager", which was designated as a national TB registry, including in the prison system in 2012...