BioClinica (United States)

To provide an ESSKA-ESA formal Consensus to help general practitioners in their daily clinical decisions regarding the diagnosis and treatment of traumatic anterior shoulder instability (TASI) according to age and timing after injury. Part 1 is dedicated to the history-taking, physical examination and imaging studies. Patients were categorised into three age groups: adolescents (<20 years), young adults (20-40 years) and older adults (>40 years). Two clinical scenarios were addressed: first-time and recurrent dislocations. A formal consensus process was followed, including a steering group (15 experts from 9 countries), a rating group (18 experts from 18 countries) and a reader group (28 experts from 13 countries). The steering group formulated 35 clinical questions, 12 of which related to Part 1. Each question was answered with a statement and grade of recommendation (A-D), based on literature and expert opinion. The rating group reviewed and refined the statements, followed by validation from the reader group for cultural adaptability. Consensus was reached with high agreement: median (range) 9 (8-9). One question received a grade A recommendation, nine were B, and two were C. Most debated topics included imaging to guide treatment decisions in first-time dislocations, assessment of glenoid bone loss, and soft tissue quality. Each age group presents unique diagnostic considerations: younger patients have higher recurrence risk and activity levels; older patients more often present with associated soft-tissue injuries. While physical exam findings were consistent across ages, associated injuries gain importance with age. The distinction between first-time and recurrent dislocations significantly impacts imaging needs. The ESSKA-ESA Consensus highlights that age and timing (first-time versus recurrent) influence the decision-making when managing TASI. All parameters related to history taking, physical exam and imaging studies should be considered according to the patient's age and the number of dislocation episodes. Level II.

Abstract Background: HER3-targeted antibody-drug conjugates (ADCs) have shown benefits in breast cancer (BC). DB-1310 is a novel ADC comprised of a humanized anti-HER3 IgG1 monoclonal antibody with a highly internalizing unique Domain I epitope, a cleavable peptide linker, and a potent DNA topoisomerase I inhibitor P1021. Initial clinical data demonstrated a manageable safety profile and encouraging anti-tumor activity, particularly in patients with EGFR-mutant NSCLC (Lisberg ASCO 2025). Here, we present the efficacy and safety results of DB-1310 in pretreated hormone receptor-positive (HR+), HER2-negative (HER2-) BC patients. Methods: In the Phase 1 part of this trial (NCT05785741), patients with advanced solid tumors, including HR+/HER2- BC, received DB-1310 monotherapy intravenously every three weeks (Q3W). Safety was the primary endpoint, with efficacy endpoints including objective response rate (ORR), duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) as secondary endpoints. Results: As of July 04, 2025, a total of 207 patients with solid tumors were enrolled and treated with DB-1310 monotherapy (1.5-6.5 mg/kg, Q3W) in Phase 1 (ECOG PS 1, 84.1%; White, 26.1%; Asian, 69.1%). Among these, 16 HR+/HER2- BC patients were enrolled (3.0-5.5 mg/kg, Q3W), with 15 of them being efficacy-evaluable, and a median prior line of systemic therapy was 2 (range, 1-7). Efficacy Results (N=15 HR+/HER2- BC patients from Phase 1): nine achieved a partial response (one pending confirmation), and four achieved stable disease, resulting in a confirmed ORR of 53.3% (95%CI: 26.59, 78.73) and a DCR of 86.7% (95%CI: 59.54, 98.34). Notably, all partial responses occurred in patients treated with 5-5.5 mg/kg (N=13), yielding an unconfirmed ORR of 69.2%, a confirmed ORR of 61.5%, and a DCR of 92.3% for this dose range. The median DoR is not reached. Median PFS is 14.78 months (95% CI: 11.60, not evaluable) and median OS is 14.69 months (95% CI: 11.89, not evaluable). Safety Results (N=207, all enrolled patients from Phase 1): The safety profile was assessed in the entire Phase 1 part. Treatment-related adverse events (TRAEs) of Grade (G) ≥ 3 occurred in 89 (43.0%) patients, and 25 patients (12.1%) had treatment-related serious adverse events. TRAEs led to dose reduction in 38 (18.4%) and discontinuation in 9 (4.3%) patients. No TRAE-related deaths were reported. Most common TRAEs (any grade/≥G3; &amp;gt;20% overall) were neutrophile count decreased (49.3%/ 26.1%), anemia (47.8%/ 6.8%), platelet count decreased (45.4%/ 15.9%), white blood cell count decreased (43.5%/ 11.1%), nausea (40.6%/ 1.0%), decreased appetite (29.5%/ 0.5%), aspartate aminotransferase increased (26.6%/ 0), alopecia (26.1%/ 0), vomiting (24.6%/ 0), and hypoalbuminemia (21.7%/ 0). Interstitial lung disease/pneumonitis occurred in 10 pts (4.8%; one Grade 2, all others G1). The safety profile in the 16 HR+/HER- BC patients was consistent with the overall Phase 1 part. Conclusion: DB-1310 showed promising anti-tumor activity in heavily pretreated HR+/HER2- BC patients. The manageable safety profile observed in the larger Phase 1 part, involving 207 patients, is consistent with that of the BC subpopulation, supporting its further development. Citation Format: Y. Yin, A. Spira, H. Lan, M. Zhao, Y. Mao, W. Yao, Y. Sun, J. Wu, X. Sun, S. Liu, H. Mu, K. Wang, Y. Qiu, E. Hamilton. First clinical data of DB-1310 (HER3-targeted antibody-drug-conjugate), in patients with pretreated hormone receptor-positive/HER2-negative breast cancer: efficacy and safety data from a phase 1/2a trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-06-17.

Abstract Background: The estrogen receptor (ER), cyclin-dependent kinase (CDK), and PI3K-AKT-mTOR (PAM) pathways are interconnected and drive hormone receptor (HR)+/HER2- advanced breast cancer (ABC). In the first line setting, endocrine therapy (ET) combined with a CDK4/6 inhibitor is the standard of care regimen for most patients with HR+/HER2- ABC. For patients in the second line setting, several inhibitors targeting components of the PAM pathway (e.g. PI3Kα, AKT, mTORC1) are approved in combination with ET. By only addressing a single target of the PAM pathway, the currently approved PI3Kα, AKT, mTORC1 inhibitors do not prevent adaptive resistance induced by the other uninhibited PAM targets. In a phase 1b clinical trial, gedatolisib, a multi-target PAM inhibitor, combined with ET and palbociclib showed promising efficacy and safety in patients with HR+/HER2- ABC, regardless of PIK3CA mutation status. Here we investigated the effects of gedatolisib and single-target PI3Kα and AKT inhibitors in combination with fulvestrant and/or palbociclib in breast cancer (BC) cell models with and without PAM pathway mutations and with varying levels of sensitivity to fulvestrant and palbociclib. Methods: Gedatolisib (pan-PI3K, mTORC1/2 inhibitor), inavolisib (PI3Kα inhibitor), capivasertib (AKT inhibitor) were tested as single agents or in combination with fulvestrant and/or palbociclib in treatment-naïve BC cell lines with or without PIK3CA mutations as well as in BC cell lines adapted to long-term treatment with fulvestrant and/or palbociclib. Cell viability, growth rate, cell cycle, DNA replication, apoptosis, and cell death were evaluated by luciferase-based and flow cytometry-based functional assays. Results: Gedatolisib reduced growth rates of treatment-naïve or fulvestrant/palbociclib-adapted BC cell lines, regardless of PIK3CA mutational status, and the addition of fulvestrant and/or palbociclib increased growth-inhibitory effects. From a functional standpoint, the gedatolisib/palbociclib/fulvestrant triplet inhibited DNA replication and/or induced apoptotic cell death more effectively than treatment with single drugs or drug doublets. The gedatolisib/palbociclib/fulvestrant triplet was more effective than PI3Kα and AKT inhibitors (inavolisib, capivasertib) combined with palbociclib and/or fulvestrant in the BC cell lines tested, regardless of PIK3CA mutational status or previous adaptation to palbociclib and/or fulvestrant. Conclusions: These results indicate that gedatolisib plus fulvestrant, with and without palbociclib, effectively controls the growth of treatment-naïve BC cells as well as BC cells adapted to palbociclib/fulvestrant treatment. Moreover, in contrast to the currently approved PI3Kα and AKT inhibitors, the gedatolisib/palbociclib/fulvestrant triplet is effective in BC cells with or without PIK3CA mutations. The combination of gedatolisib with ET and a CDK4/6 inhibitor is being evaluated in two ongoing Phase 3 clinical trials as first-line (VIKTORIA-2) or second-line (VIKTORIA-1) treatment of HR+/HER2- ABC with or without PIK3CA mutations. The non-clinical results presented here provide a strong mechanistic rationale for these clinical studies. Citation Format: S. Rossetti, A. Broege, L. Davis, M. Seibel, S. Stokke, J. Molden, I. Gorbatchevsky, B. Sullivan, L. Laing. Functional analysis of gedatolisib combined with fulvestrant and/or palbociclib in breast cancer cell models adapted to estrogen receptor and/or CDK4/6 inhibitors [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-11-30.

Objective To evaluate the characteristics of psychotropic medication use under pro re nata (PRN, or "as needed") orders for patients treated in a psychogeriatric hospital ward. Design A retrospective point-prevalence, cross-sectional study comparing PRN order parameters with standards published by the Australian Commission on Quality and Safety in Health Care. Setting An inpatient psychogeriatric unit in a South Australian public teaching hospital. Participants Data were collected from inpatient charts and case notes during a single, continuous 24-hour sampling period. All PRN medication orders were reviewed, including documentation of actual drug administrations, and these were matched with the associated clinical outcomes. Data were collected from 26 patients, for whom a total of 38 PRN psychotropic medication orders were analyzed. Result The majority of PRN orders (81%) met the criteria of the relevant Australian National Standards; however, of the 19 medication administration occasions, only 26% had adequate documentation that included both specific reasons for administration and the outcomes associated with the PRN treatment. Overall, it was noteworthy that a relatively high proportion of these PRN orders (61%) were actioned during the 24-hour snapshot period. Conclusion The use of PRN psychotropic medications remains an important component in the treatment of older patients with mental illness. Continued efforts to improve and optimize the documentation associated with PRN psychotropic drug administration warrant ongoing attention.

This study aimed to evaluate the efficacy and biocompatibility of various absorbable threads from Hans BioMed for facial lifting in a Sprague Dawley rat model, focusing on collagen production, inflammatory responses, and overall skin remodeling. Six types of absorbable threads, PCL, PDO, PDLLA, PLCL, and two P4HB variants (55 and 90% elongation) from Hans BioMed, were analyzed using histological, immunohistochemical, and molecular methods for observation, including 1, 2, 4, and 8weeks post-thread insertion. Total 140 rats were used with 20 rats for each thread group, in which five rats for each time point. Firstly, inflammatory markers, including TNF-α and IL-6, peaked at 1week and subsided significantly by 8weeks, confirming the safety profile of all threads. The overall results demonstrated that all threads induced collagen formation and reduced inflammation over time. Notably, collagen 1 levels in all testing groups steadily increased from 2 to 8weeks, complemented by reduced metalloproteinase expression, indicating preserved collagen stability, observed in Western Blotting. Additionally, RT-PCR highlighted increased expression of collagen-related genes and elevated TGF-β and α-SMA levels, suggesting enhanced skin remodeling capabilities. All tested absorbable threads promoted collagen formation and showed minimal response to inflammation over time. The findings provide a foundation for developing advanced thread-lifting products, offering improved skin elasticity, firmness, and collagen synthesis outcomes. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://link.springer.com/journal/00266 .

Introduction In chronic granulomatous disease (CGD), Aspergillus is the most common cause of invasive fungal infections and accounts for a high percentage of mortality. Methods The current study included 45 patients with a genetic diagnosis of CGD recruited between 2005 and 2024 from seven public hospitals in four Mexican cities. Results We recruited 45 patients of CGD with invasive aspergillosis (IA) events. The median age between the first CGD manifestation and first aspergillosis event was 65 months. Mortality rate was 57.7% for proven aspergillosis events, 23.1% for probable events, and 19.2% for possible events (p = 0.038). Aspergillus fumigatus was the most common species. Of the 45 patients, 26 (58%) had one IA event, nine (20%) had two, five (11%) had three, and five (11%) had four IA events. The median time between the first and second events was 35 months (15–65), between the second and third events was 26 months (17.5–32.5), and between the third and fourth events was 22 months (15.5–43.5). Of the 78 IA events, 43 (55%) were treated with monotherapy, 16 (20.5%) with dual therapy, 15 (19.2%) with triple therapy, three (3.8%) with quadruple therapy, and one (1.5%) with quintuple therapy. Twenty-six (58%) of the 45 patients died, out of which 18 (69%) had IA. The median age at death was 107.5 months (44.7–196). Overall survival of the 45 patients was 80.8% at 64 months. Conclusions The high mortality rate of IA in CGD patients could be reduced by early suspicion, initiating correct antifungal treatment over a long period, and considering the performance of hematopoietic stem cell transplantation.

Coronary artery disease remains one of the leading causes of morbidity and mortality worldwide. Timely and accurate diagnosis is crucial for selecting optimal therapeutic interventions and improving patient outcomes. Various imaging modalities are employed for this purpose, while hybrid imaging techniques combine the advantages of individual modalities, providing a more detailed assessment of the myocardium’s morphological and functional characteristics. This paper provides an overview of the available imaging methods for diagnosing coronary artery disease, with a particular emphasis on the role and application of hybrid techniques as a modern approach that contributes to more effective therapy planning and reduces the need for multiple diagnostic procedures. Special attention is given to the role of radiologic technologists in the entire diagnostic process, their daily professional responsibilities, and the importance of continuous professional development in the use of hybrid systems.