BACKGROUND: There are scarce data available on upadacitinib in children with Crohn's disease (CD). AIM: To evaluate the effectiveness and safety of upadacitinib as an induction therapy in paediatric CD. METHODS: This was a multicentre retrospective study between 2022 and 2024 of children treated with upadacitinib for induction of remission of active CD conducted in 30 centres worldwide affiliated with the IBD Interest and Porto group of the ESPGHAN. We recorded demographic, clinical and laboratory data and adverse events (AEs) at week 8 post-induction. The analysis of the primary outcome was based upon the intention-to-treat (ITT) principle. RESULTS: We included 100 children (median age 15.8 [interquartile range 14.3-17.2]). All were previously treated with biologic therapies including 89 with ≥ 2 biologics. At the end of the 8-week induction period, we observed clinical response, clinical remission and corticosteroid- and exclusive enteral nutrition-free clinical remission (CFR) in 75%, 56% and 52%, respectively. By the end of induction, 68% had achieved normalisation of C-reactive protein, and 58% had faecal calprotectin (FC) < 150 mcg/g. There was combined CFR and FC remission in 13/31 children with available data at 8 weeks (13% of the ITT population). AEs were recorded in 24 children; the most frequent was acne in 12. Two AEs (severe acne and hypertriglyceridemia) led to discontinuation of therapy. CONCLUSION: Upadacitinib is an effective induction therapy for refractory paediatric CD. Efficacy should be weighed against the potential risks of AEs.
- MeSH
- Crohn Disease * drug therapy MeSH
- Child MeSH
- Heterocyclic Compounds, 3-Ring * therapeutic use MeSH
- Remission Induction * methods MeSH
- Humans MeSH
- Adolescent MeSH
- Retrospective Studies MeSH
- Treatment Outcome MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
Methoxphenidine (MXP) is classified as a new psychoactive substance that has recently emerged on the illicit drug market. Understanding the pharmacological and behavioural profiles of newly emerging drugs is essential for a better understanding of their psychotropic effects and potential toxicity. Therefore, in this study, we investigated a broad range of effects of acute MXP administration: pharmacokinetics in the brain and serum; behaviour (open field and prepulse inhibition), systemic toxicity (lethal dose; LD 50), and histopathology changes in parenchymal organs of Wistar rats. MXP rapidly crossed the blood-brain barrier, reaching peak median concentrations in both serum and brain 30 min post-administration, followed by an elimination phase with a half-life of 2.15 h. Locomotor activity in the open field test displayed a dose-response effect at low to moderate doses (10-20 mg/kg MXP). At higher doses (40 mg/kg), locomotor activity decreased. All doses of MXP significantly disrupted prepulse inhibition and the effect was present during the onset of its action as well as 60 min after treatment. Additionally, MXP demonstrated moderate acute toxicity, with an estimated LD50 of 500 mg/kg when administered subcutaneously. In summary, MXP exhibited a profile similar to typical dissociative anesthetics, producing stimulant and anxiogenic effects at lower doses, sedative effects at higher doses, and disrupting sensorimotor gating. The accumulation of MXP in brain tissue is likely to contribute to acute intoxication in humans, potentially leading to negative experiences. Our findings highlight the potentially dangerous effects of recreational MXP use and underscore the risks of inducing serious adverse health outcomes.
- MeSH
- Behavior, Animal drug effects MeSH
- Rats MeSH
- Lethal Dose 50 MeSH
- Brain drug effects metabolism MeSH
- Piperidines pharmacokinetics pharmacology MeSH
- Motor Activity drug effects MeSH
- Rats, Wistar * MeSH
- Prepulse Inhibition drug effects MeSH
- Open Field Test drug effects MeSH
- Dose-Response Relationship, Drug * MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
RNA secondary (2D) structure visualization is an essential tool for understanding RNA function. R2DT is a software package designed to visualize RNA 2D structures in consistent, recognizable, and reproducible layouts. The latest release, R2DT 2.0, introduces multiple significant features, including the ability to display position-specific information, such as single nucleotide polymorphisms or SHAPE reactivities. It also offers a new template-free mode allowing visualization of RNAs without pre-existing templates, alongside a constrained folding mode and support for animated visualizations. Users can interactively modify R2DT diagrams, either manually or using natural language prompts, to generate new templates or create publication-quality images. Additionally, R2DT features faster performance, an expanded template library, and a growing collection of compatible tools and utilities. Already integrated into multiple biological databases, R2DT has evolved into a comprehensive platform for RNA 2D visualization, accessible at https://r2dt.bio.
Bone strength is reduced In various neuromuscular disorders (NMDs). We aimed to assess the awareness and practice of bone strength management in NDMs among clinicians and patients. We performed two online surveys; among health care providers (HCPs) of the European Reference Network for Neuromuscular Disorders (ERN EURO-NMD) and among patients. The survey among 52 HCPs showed that awareness of potentially impaired bone strength in people with NMDs was reasonable to good: the vast majority of HCPs asked often or almost always about bone fractures during history-taking (81 %). Bone strength was less often assessed: often or almost always at diagnosis (50 %) and at follow-up (58 %). Medical training on this topic was considered poor to very poor in 50 % of HCPs. Prevention and treatment of reduced bone strength was variable and multidisciplinary care was sub-optimal. The survey among 581 patients provided important additional insights. Many patients were followed-up outside ERN EURO-NMD centers and treatment was variable. These parallel surveys provided a broad view on the awareness and management of bone strength in people with NMDs. The findings are expected to increase the appreciation of this important aspect of NMD care, and direct future research foci and care guidelines.
- MeSH
- Adult MeSH
- Bone Density * physiology MeSH
- Middle Aged MeSH
- Humans MeSH
- Neuromuscular Diseases * complications physiopathology therapy epidemiology MeSH
- Surveys and Questionnaires MeSH
- Aged MeSH
- Awareness * MeSH
- Health Knowledge, Attitudes, Practice * MeSH
- Health Personnel MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe MeSH
OBJECTIVE: This study aimed to evaluate the association between pre-operative progesterone receptor (PR) and p53 expression and prognosis in pre-operative grade 2 endometrioid endometrial carcinoma compared with grade 1 and grade 3 carcinomas. METHODS: Three European endometrial carcinoma cohort studies were included. Patients with pre-operative grade 2 endometrioid carcinoma and known pre-operative PR and p53 status were included (n = 400), as were patients with pre-operative grade 1 (n = 602) or grade 3 (n = 148) endometrioid carcinomas. Kaplan-Meier and Cox regression analyses were performed to analyze disease-specific and disease-free survival. RESULTS: Patients with pre-operative grade 2 endometrial carcinoma and wild-type p53 plus PR-positive expression showed a similar 7-year disease-specific survival to grade 1 endometrial carcinoma patients (95.8% vs 97.5%, p = .13), while the 7-year disease-specific survival of patients with grade 2 endometrial carcinoma with p53 aberrant and/or negative PR expression (83.5%) was significantly lower (p < .001). The combination of these markers was an independent prognostic factor in multivariate Cox regression analyses. CONCLUSIONS: The prognostic impact of pre-operative p53 and PR expression in patients with grade 2 endometrioid endometrial carcinoma supports a modified binary grading system in which grade 2 patients should be pre-operatively classified as low- or high-grade depending on p53 and PR expression.
- MeSH
- Adult MeSH
- Carcinoma, Endometrioid * pathology metabolism surgery mortality MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Biomarkers, Tumor metabolism MeSH
- Tumor Suppressor Protein p53 * metabolism biosynthesis MeSH
- Endometrial Neoplasms * pathology metabolism surgery mortality MeSH
- Prognosis MeSH
- Receptors, Progesterone * metabolism biosynthesis MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Neoplasm Grading MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: Nerve grafting with the sural nerve is a standard treatment method for radial nerve injury that requires another incision at the lateral ankle distal from the injured upper limb. The aim of this study was to investigate the common trunk (CTCB) of the inferior lateral brachial cutaneous nerve (ILBCN) and posterior antebrachial cutaneous nerve (PACN) as a possible donor inside the lateral intermuscular septum. MATERIALS AND METHODS: The arms and legs of 8 formalin-embalmed cadaver specimens were studied. The radial nerve, common trunk of the ILBCN and PACN, and the sural nerve were identified and measured in length and diameter. For histological examination, nerve samples from 6 fresh cadavers were harvested and processed for further axonal counting. RESULTS: The average length of the CTCB was 114.92 ± 18.9 mm. To match the diameter of the radial nerve at its proximal third, 3 cables of CTCB graft were necessary, which corresponds to a defect length of 3.8 cm. At the level of the distal third, the number of grafts was reduced to 2 with a corresponding defect length of 5.7 cm. The radial nerve contained 15162 ± 318 axons, and the CTCB comprised 3959 ± 176 axons. To match the axon count of the recipient nerve, 4 grafts of CTCB were necessary, which corresponded to a defect length of 2.8 cm. CONCLUSION: CTCB is a consistent and easily dissected cutaneous nerve branch of the radial nerve that can be used for bridging small gaps after neuroma-in-continuity in radial nerve palsy.
- MeSH
- Middle Aged MeSH
- Humans MeSH
- Cadaver MeSH
- Nerve Transfer * methods MeSH
- Radial Nerve * surgery anatomy & histology injuries MeSH
- Sural Nerve * transplantation anatomy & histology MeSH
- Aged MeSH
- Plastic Surgery Procedures * methods MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Donor nerve selection is a crucial factor in determining clinical outcomes of facial reanimation. Although dual innervation approaches using two neurotizers have shown promise, there is a lack of evidence-based comparison in the literature. Furthermore, no animal model of dual reinnervation has yet been published. This study aimed to establish such a model and verify its technical and anatomical feasibility by performing dual-innervated reanimation approaches in Wistar rats. METHODS: Fifteen Wistar rats were divided into four experimental groups and one control group. The sural nerve was exposed and used as a cross-face nerve graft (CFNG), which was then anastomosed to the contralateral buccal branch of the facial nerve through a subcutaneous tunnel on the forehead. The CFNG, the masseteric nerve (MN), and the recipient nerve were coapted in one or two stages. The length and width of the utilized structures were measured under an operating microscope. Return of whisker motion was visually confirmed. RESULTS: Nine out of the eleven rats that underwent surgery survived the procedure. Whisker motion was observed in all experimental animals, indicating successful reinnervation. The mean duration of the surgical procedures did not differ significantly between the experimental groups, ensuring similar conditions for all groups. CONCLUSIONS: Our experimental study confirmed that the proposed reanimation model in Wistar rats is anatomically and technically feasible, with a high success rate, and shows good prospects for future experiments.
- MeSH
- Facial Paralysis * surgery MeSH
- Rats MeSH
- Disease Models, Animal MeSH
- Facial Nerve * surgery physiology MeSH
- Sural Nerve surgery MeSH
- Rats, Wistar MeSH
- Nerve Regeneration * physiology MeSH
- Vibrissae physiology innervation MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Background/Objectives: The DIEP flap is among the preferred techniques in autologous breast reconstruction due to better long-term outcomes, including higher satisfaction and more natural breast shape compared to implant-based breast reconstruction. With the rise in genetic testing, bilateral DIEP reconstructions are becoming more common, though they carry a higher risk of complications. This study aims to compare the risks between unilateral and bilateral procedures to improve surgical decision-making. Methods: A retrospective, single-center review was conducted on female patients who underwent DIEP flap breast reconstruction between January 2018 and May 2024. The study included patients with complete medical records and follow-up data, excluding those with incomplete records. Patient characteristics, operative details, and complications were thoroughly analyzed, with donor site complications assessed per patient and recipient site complications per breast. Results: During the study, 141 DIEP flaps were performed on 114 women, with 87 unilateral and 27 bilateral reconstructions. Age and BMI were similar between groups. However, chemotherapy was more common in the bilateral group (85% vs. 47%, p = 0.0011). Operative time was significantly longer in bilateral procedures (650 vs. 460 min, p < 0.0001). There were no statistically significant differences in recipient and donor site complications across groups. The hospital stay was significantly longer in the bilateral group (11 vs. 8.8 days, p = 0.024). Conclusions: Bilateral and unilateral DIEP flap breast reconstructions have similar complication and early take-back rates.
- Publication type
- Journal Article MeSH
Ischemic stroke is a leading cause of mortality and long-term disability globally. One of its aspects is the breakdown of the blood-brain barrier (BBB). The disruption of BBB's integrity during stroke exacerbates neurological damage and hampers therapeutic intervention. Recent advances in regenerative medicine suggest that mesenchymal stem cells (MSCs) derived extracellular vesicles (EVs) show promise for restoring BBB integrity. This review explores the potential of MSC-derived EVs in mediating neuroprotective and reparative effects on the BBB after ischemic stroke. We highlight the molecular cargo of MSC-derived EVs, including miRNAs, and their role in enhancing angiogenesis, promoting the BBB and neural repair, and mitigating apoptosis. Furthermore, we discuss the challenges associated with the clinical translation of MSC-derived EV therapies and the possibilities of further enhancing EVs' innate protective qualities. Our findings underscore the need for further research to optimize the therapeutic potential of EVs and establish their efficacy and safety in clinical settings.
- Publication type
- Journal Article MeSH
- Review MeSH
This study investigated the combined impact of family dynamics and school environments on physical activity levels in children aged 3-9 years across distinct segments of the school day. Conducted as part of the FAMIPASS project in the Czech Republic, the study collected data in 2022 and 2023 from 502 families affiliated with 36 preschools and primary schools. The device-based monitoring of movement behaviors in children and their parents was conducted over a one-week period using ActiGraph accelerometers, complemented by detailed family questionnaires. Regression analysis revealed that parental physical activity, BMI, and education level significantly influenced children's moderate-to-vigorous physical activity, with educated parents more likely to raise active children. Active transport to school emerged as a key factor associated with higher child activity levels specifically in the time segment before school. This research underscores the role of family and school as critical arenas for promoting health and physical activity. These insights highlight the need for integrated family-school strategies to foster healthy activity habits in children, thereby laying the groundwork for a more active generation.
- Publication type
- Journal Article MeSH
