The present guideline summarizes all aspects of patch testing for the diagnosis of contact allergy in patients suspected of suffering, or having been suffering, from allergic contact dermatitis or other delayed-type hypersensitivity skin and mucosal conditions. Sections with brief descriptions and discussions of different pertinent topics are followed by a highlighted short practical recommendation. Topics comprise, after an introduction with important definitions, materials, technique, modifications of epicutaneous testing, individual factors influencing the patch test outcome or necessitating special considerations, children, patients with occupational contact dermatitis and drug eruptions as special groups, patch testing of materials brought in by the patient, adverse effects of patch testing, and the final evaluation and patient counselling based on this judgement. Finally, short reference is made to aspects of (continuing) medical education and to electronic collection of data for epidemiological surveillance.
LBA5500 Background: Optimal timing of cytoreduction in non-frail patients (pts) with seemingly resectable stage IIIB-IVB ovarian, tubal, and peritoneal carcinoma (OC) remains controversial. Methods: TRUST is an international randomized multicenter phase III trial in pts with stage IIIB-IVB OC and good performance status (ECOG 0/1) comparing primary cytoreductive surgery (PCS) followed by 6 cycles of intravenous (iv) chemotherapy to 3 cycles of neoadjuvant iv chemotherapy (NACT) followed by interval cytoreductive surgery (ICS) and 3 further iv cycles. Maintenance treatment with bevacizumab and/or PARP inhibitors was allowed if selection criteria was similar for both arms. Pts were eligible for the study if preoperative clinical and radiologic assessment identified them as potential candidates for PCS. To ensure surgical quality, participating centers complied with an onsite surgery quality assurance audit, had adequate infrastructure, surgical proficiency (complete resection rates ≥50% in PCS) and sufficient volume (≥36 PCS/year). The intent to treat analysis population included all eligible pts with confirmed stage IIIB-IVB disease. The primary endpoint was overall survival (OS). Superiority was tested using a two-sided stratified log-rank test with significance level 0.05. Secondary endpoints were progression-free survival (PFS) and surgical complications. Results: A total of 688 eligible pts (median age: 63y; range: 32-83) underwent randomization: 345 were assigned to PCS and 343 to NACT/ICS. 91% had high-grade serous histology. Complete resection was achieved in 61.7%/62.9% of all randomized/all operated pts in the PCS group and 72%/76.6% in the ICS group. Median PFS was 22.2 months in the PCS group, and 19.7 months in the ICS group (HR 0.80 95%CI: 0.66-0.96; p=0.02). Median OS was 54.3 months in the PCS group and 48.3 months in the ICS group (HR 0.89 95%CI: 0.74-1.08; p=0.24). Pts with complete cytoreduction after PCS had the most favorable outcome, with a median PFS and OS of 27.9 and 67.0 months, respectively. A long-term benefit from PCS was seen in all analyzed subgroups. The benefit of PCS was most prominent in stage III pts (n=468): median PFS for PCS vs ICS, 26.3 vs 21.4 mos; median OS for PCS vs ICS, 63.7 vs 53.2 months. Major postoperative complication rates were acceptable, with a 30-day postoperative mortality rate of < 1% in both groups. Conclusions: In expert centers with proven surgical quality, PCS followed by iv chemotherapy resulted in a significantly longer median PFS and a numerically longer OS compared to NACT/ICS in non-frail OC pts. Although statistical significance in the primary endpoint was not reached, this is the first randomized trial to show a benefit of PCS over ICS. This benefit is likely to be associated with the high complete resection rate, reinforcing PCS as a standard of care in non-frail pts with seemingly resectable advanced OC. Clinical trial information: NCT02828618 .
Peripheral nerves are increasingly recognized as regulators of vascular pathology, shaping arterial tone, inflammation, and structural remodeling. This review delineates how neural circuits interface with the aortic wall, considers sympathetic and sensory pathways in atherosclerosis and aneurysm pathophysiology, and discusses emerging experimental approaches and therapeutic strategies. Autonomic and sensory neural circuits are increasingly recognized as modulators of arterial disease. In experimental atherosclerosis, neuroimmune crosstalk shapes vascular inflammation and influences plaque stability. Limited available evidence from human and experimental studies suggest increased sympathetic innervation within aneurysm tissue. In preclinical models, aneurysm remodeling was linked with sympathetic input, and interventions that reduce noradrenergic signaling via sympathetic denervation or pharmacological adrenergic blockade attenuated disease severity. Improved understanding of the role for innervation in vascular pathophysiology may open therapeutic opportunities, including neuromodulation and pharmacological interventions. Clarifying sources of heterogeneity between models and clinical data can potentially refine therapeutic targets and patient selection, and advance opportunities for precision interventions. Peripheral neural circuits are integral to vascular homeostasis in health and disease, interfacing with blood vessels and regulating their physiology. Converging human and preclinical evidence implicates sympathetic innervation in disease development, and that dampening adrenergic signaling via denervation or adrenergic blockade may mitigate disease progression. This review discusses mechanistic neuroimmune crosstalk across atherosclerosis and aneurysm biology and outlines some potential translational opportunities. Together, the advances position neurovascular crosstalk as a potentially tractable axis for disease-modifying interventions.
Abstract Transgenic mouse models expressing predefined T-cell receptors (TCRs) have been instrumental in advancing our understanding of T-cell biology. However, these traditional models rely on random genomic insertion of large constructs, require labor-intensive embryo manipulation, and frequently result in aberrant TCR expression and phenotypes. These limitations render traditional models insufficient to meet the mounting demands for rapid and precise model systems to evaluate TCR specificities. In this study, we developed a streamlined method that uses adeno-associated virus (AAV) and CRISPR/Cas9-mediated genome editing to precisely integrate pre-rearranged TCRα/β sequences into the mouse TCRβ (Trb) locus, enabling the rapid generation of TCR knock-in mice with physiological TCR expression and functional T-cell differentiation upon antigenic challenge. This approach bypasses the need for screening multiple founders for faithful TCR expression, enhancing the versatility and utility of monoclonal TCR mice in basic immunology and preclinical research, such as in the fields of cancer immunotherapy and vaccine development.
The developmental trajectories of internalizing and externalizing symptoms, including ADHD, vary widely among individuals, yet the factors that contribute to these diverse patterns are not fully understood. Our specific objectives are to empirically identify developmental trajectories of internalizing, externalizing, and ADHD symptoms from ages 4 to 15, and to explore how early-life risk factors are linked to these trajectory groups. The study included 551 mother–child pairs of the Rhea mother–child cohort in Crete, Greece. Children’s internalizing, externalizing, and ADHD symptoms were evaluated using maternal reports at ages 4 (Strengths and Difficulties Questionnaire, ADHD Test), 6, 11 and 15 years (Child Behavior Checklist, Conners’ Parent Rating Scale-Revised). Group-based trajectory modeling was applied to identify trajectory groups from 4 to 15 years and multinomial logistic regression models were implemented to examine the associations between early-life risk factors and group trajectories. The analysis revealed four distinct trajectories for each outcome (internalizing, externalizing, and ADHD symptoms): stable low, high-decreasing, low-increasing, and stable high symptoms. Furthermore, several early-life sociodemographic and perinatal factors, such as sex, maternal and paternal age, paternal education, maternal smoking during pregnancy, and breastfeeding duration were significantly linked to the development of internalizing, externalizing, and ADHD symptoms. The study highlights the complex and dynamic nature of emotional and behavioral symptom development and the critical role of early-life determinants in shaping these trajectories. Findings suggest that early identification and intervention are crucial for preventing the persistence of psychopathology into adolescence.
