401 General Military Hospital of Athens

Abstract Background Upadacitinib (UPA) is a reversible selective Janus kinase 1 (JAK 1) inhibitor indicated for the treatment of moderate to severe inflammatory bowel disease (IBD). Common adverse events (AEs) include upper respiratory tract infections, anaemia and increased blood creatine phosphokinase (CPK), whereas concern has been raised about cardiovascular events (CV). Additionally, uncommon adverse events may involve herpes zoster and acne. We present the real-world experience of UPA in patients with IBD, from two tertiary centres in Greece, focusing on safety. Methods We retrospectively reviewed the medical records of IBD patients who continue or had received UPA in our departments. Demographic and clinical characteristics, as well as reported AEs during UPA treatment, were documented. Severity and frequency of AEs were monitored according to standard clinical practice. Results We identified 77 patients on UPA treatment: 23 (29.9%) experienced at least 1 AE during treatment; 69.8% were male, with a mean age of 36.8 years (±11.9), 47.8% with CD, and a median disease duration of 9 years (IQR 8.5). Demographics and clinical characteristics are summarised in Table 1. A total of 30 AEs were recorded. Respiratory tract infections represented the most prevalent AE (36.3%), followed by any other infection (16.6%) and metabolic disorders (hyperlipidaemia) (13.3%) (Fig. 1). Fourteen AEs (46.7%) manifested during the induction phase of the treatment (45mg), 20% led eventually to permanent discontinuation of UPA (due to recurrent respiratory tract infections, severe acne, small bowel perforation and cutaneous staphylococcus infection), 46.6% required both temporary drug interruption and AE focused treatment and 3.33% improved after dosage adjustment. In the remaining cases, therapy withdrawal was unnecessary. Four out of 30 were documented as serious AEs. No death has been reported. Patients who experienced serious adverse events were all male, and 75% of them had previously received anti–TNFα therapy. Potential risk factors for the development of adverse events, such as smoking, age, duration of the disease and BMI, were not shown to have a statistically significant difference. No major cardiac or thrombotic events were observed, nor was any cancer case reported. At this time point, 73.1% of the patients continue UPA treatment. Conclusion Most adverse events were non-serious (86.7%) and manageable after a temporary interruption of UPA or after dosage adjustment. Most of them were consistent with the drug’s known safety profile. Further studies are warranted to validate these observations and better characterise the treatment’s safety profile. Conflict of interest: Mr. Neokleous, Antonis: No conflict of interest Pagoni, Anna: No conflict of interest Liatsos, Christos: No conflict of interest Kyriakos, Nikolaos: No conflict of interest Zacharopoulou, Eirini: No conflict of interest Tsokanta, Konstantina: No conflict of interest Aravantinoy Koytsoyvi, Artemis Stavroyla: No conflict of interest Tzouvala, Maria: No conflict of interest

Within the framework of the ongoing development of application of Machine Learning models in Medicine and Physical Therapy, the development of accurate prognosis algorithms for postoperative patients during the rehabilitation phase remains an area requiring further refinement. This paper examines hybrid Deep Learning models that integrate Convolution Neural Networks, Long Short-Term Memory and Gated Recurrent Unit networks, as well as genetic algorithm optimization for feature selection for predicting the time needed for a patient to rehabilitate. Patient data included features like age, passive range of available movements (preoperative and postoperative) and total rehabilitation time. Genetic Algorithm optimization for feature selection indicated that 4 out of the 16 available features are adequate for predicting rehabilitation time. Hybrid Deep Learning models achieved a Root Mean Squared Error (RMSE) of 12 days (less than 0.4 months) in rehabilitation time prediction, demonstrating good performance on a relatively small dataset of 120 patients.

IssueDespite evidence supporting early rehabilitation integration in trauma care, systematic approaches remain inconsistent across European healthcare systems. Implementation gaps between policy frameworks and clinical practice may compromise patient outcomes and increase costs, requiring evidence-based analysis of effective integration strategies.DescriptionThis policy analysis examined rehabilitation integration across six countries (UK, Netherlands, Italy, Ireland, Norway, Ukraine) using clinical guidelines, service specifications, research studies, and registry data spanning 2013-2025, focusing on service integration, workforce development, information systems, leadership structures, and financing mechanisms.ResultsIntegration approaches varied significantly. The UK operates the most comprehensive multilevel framework combining NICE NG211 guidelines, D15/S/a specifications, 22 regional networks with dedicated leadership, and mandatory TARN monitoring. The Netherlands demonstrated strongest economic evidence through their Transmural Trauma Care Model, achieving €875-€1,553 cost savings with 17% quality of life improvement and 23% pain reduction. Norway’s registry system enables quality improvement, though research reveals poor guideline adherence requiring intervention. Italy shows policy evolution from basic integration (2015) to intensive rehabilitation guidelines (2024). Ukraine demonstrates adaptive emergency frameworks through international cooperation.LessonsPolicy frameworks are insufficient without implementation monitoring. Norway’s experience shows registries and guidelines require active intervention. Successful integration requires multilevel coordination, research validation with economic evidence, dedicated leadership, and systematic monitoring addressing policy-practice gaps.Key messages• Policy frameworks require implementation architecture: The UK’s approach combining guidelines, specifications, network coordination, and quality assurance represents optimal design, while Norway’s gaps demonstrate necessity of systematic monitoring.• Economic validation supports investment: The Netherlands’ TTCM provides evidence that systematic integration achieves clinical improvement and cost reduction, creating compelling arguments for healthcare investment.TopicRehabilitation, trauma care, comparative analysis.

The results of a previous phase IIa trial suggested efficacy of the anti-C5a compound vilobelimab in a small number of patients with severe hidradenitis suppurativa (HS) refractory to adalimumab treatment. To study the efficacy of vilobelimab in a larger-scale randomized phase IIb trial (SHINE) of patients with moderate-to-severe HS. In total, 177 patients with moderate-to-severe HS were treated either with placebo or one of four doses of vilobelimab, a monoclonal antibody that targets the complement split product C5a. Hidradenitis Suppurativa Clinical Response (HiSCR) at 16 weeks was the primary endpoint. Those who achieved HiSCR switched to open-label low-dose vilobelimab; those who did not were switched to medium-dose vilobelimab. The trial was registered with the EU Clinical Trials Register (EudraCT number 2017-004501-40) and ClinicalTrials.gov (NCT03487276). The study did not meet the primary endpoint, perhaps due, in part, to an unexpectedly high HiSCR placebo response rate of 47.1%. HS flares decreased and post hoc analysis showed that high-dose vilobelimab significantly decreased the median draining tunnel counts and IHS4 score by 63%. Following the switch to medium-dose vilobelimab at week 16, 45.5% of those who did not respond to treatment achieved HiSCR at week 40. Compared with placebo, vilobelimab treatment did not result in significant HiSCR improvements in patients with moderate-to-severe HS. Post hoc analysis revealed significant effects for the highest tested dose on draining tunnel reduction and IHS4 score, which captures reductions in draining tunnels. These findings warrant further investigation.

Background/Objectives: The aim was to provide a comprehensive, systematic review on the Lateral Extra-articular Tenodesis (LET) methods used in anterior cruciate ligament (ACL) reconstruction in the light of recent data. Methods: To identify all of the essential studies that reported relevant data concerning primary outcomes: indications for surgery, surgical technique, graft type, fixation method, and tibial fixation location, an extensive search of the major and significant electronic databases (PubMed, Cochrane Central, ScienceDirect, Web of Science, Embase) was performed by three independent authors. A systematic investigation was conducted in November 2023, with no limits regarding the year of publication. After the database search, three independent reviewers screened all the papers, which followed strictly the inclusion and exclusion criteria, identifying a title, abstract, and full text concerning LET, surgical technique, femoral attachment, tibial attachment, graft type, fixation method, knee angle during fixation, and graft tension at fixation in ACL reconstruction. A systematic review of the collected literature was carried out according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Study quality was assessed using the Cochrane Risk of Bias Tool. Results: Of the 35 papers reviewed, seven surgical techniques of LET differing in the way the procedure was performed were separated. The majority of papers were from Italy (n = 11), USA (n = 3), France (n = 3), and Canada (n = 3). The number of total participants across all studies was 6253. The majority of studies (17 papers) used the Lemaire modified procedure, and 10 papers used the MacIntosh technique modified by the Coker–Arnold approach. Most of the papers mentioned fixation location on the lateral distal part of the femur including six articles referring directly to lateral femoral epicondyle. Most authors (25 papers) defined tibial attachment as Gerdy’s tubercle. The most common graft was the iliotibial band and fixation method was sutures. The types of fixation in the surgical techniques of the collected papers were Sutures, Staples, Anchor, Interference screw, K-wire, Bioabsorbable Screw and Titanium Screw with a serrated polyethylene washer. Conclusions: Despite variability in technique, the Lemaire-modified procedure emerged as the preferred approach for Lateral Extra-articular Tenodesis, suggesting a general consensus around its reliability and reproducibility in clinical practice. The frequent use of the iliotibial band as graft material reflects its accessibility and suitability for reinforcing anterolateral stability. Similarly, the consistent use of sutures and fixation at Gerdy’s tubercle may indicate a favorable balance between technical ease and biomechanical strength. The variability in femoral fixation points—either at the lateral femoral condyle or epicondyle—highlights the ongoing debate or surgeon preference, underscoring the need for further comparative studies to establish optimal fixation strategy. Collectively, these patterns may help guide surgical decision-making, particularly when tailoring procedures to individual patient anatomy or surgical expertise.

Radiotherapy (RT) is an integral component of various multidisciplinary treatment approaches for pelvic malignancies, used both in the radical and adjuvant setting. Despite the improvement of radiotherapy modalities, pelvic radiotherapy often induces permanent erectile dysfunction (ED). However, post-treatment ED receives little medical attention, since patient follow-up focuses mainly on cancer recurrence surveillance. The present review aims to summarize the current treatment modalities against radiation-induced erectile dysfunction (RIED) for patients who have received pelvic radiotherapy. A literature review on emerging treatment strategies for RIED was conducted to summarize existing evidence. Research in medical literature was conducted through the PubMed Central databases, from 1996 up until June 2024, in the English language. All relevant clinical trials on RIED management were included. The efficacy of PDE5i was investigated by 12 research studies. The majority of studies revealed that PDE5i have a potentially positive effect on maintaining EF, mainly in the shortterm after pelvic RT. Despite penile prostheses' high efficacy, their role remains limited due to various factors. Regarding yoga, a randomised clinical trial demonstrated clinical effectiveness only during the first 4 weeks of the twice/week regimen of sessions. Treatment strategies for RIED range from oral medication to more invasive treatment modalities that present high efficacy. Penile prosthesis remains the most invasive, yet the most effective and definitive treatment. Stem cell therapy, platelet-rich plasma intracavernosal injections, and penile vibratory stimulation feature an efficient profile, but their beneficial role has not yet been established. Further randomized controlled trials are required to assess the effectiveness of these interventions. Establishing strategies for the needs of survivors with RIED should also be prioritized in the therapeutic management, because patients' quality of life can be substantially improved.

This was a clinical study of total neoadjuvant therapy (TNT) for rectal cancer. To assess the use and outcomes of TNT in routine practice. This international, multicenter study was conducted at 61 centers across 21 countries and included consecutive patients treated off trial with TNT for stage II/III rectal adenocarcinoma from September 2012 to December 2023. Data were analyzed between August and October 2024. TNT, defined as the delivery of radiotherapy and nonradiosensitizing chemotherapy before surgery or watch and wait. The primary outcome was type of TNT administered. Secondary outcomes were patient characteristics, treatment adherence, safety, and efficacy overall and by type of TNT in the entire population and after propensity vector matching. A total of 1585 patients (588 female [37.1%]; median [IQR] age, 61 [53-68] years) were included, 1260 (79.5%) of whom had 1 or more high-risk features (eg, cT4, cN2, extramural venous invasion, threatened/involved mesorectal fascia, and lateropelvic lymphadenopathy). Patients were treated with the PRODIGE 23-like regimen (FOLFIRINOX/FOLFOXIRI followed by long-course chemoradiotherapy) (271 [17.7%]), RAPIDO-like regimen (short-course radiotherapy followed by consolidation FOLFOX/CAPOX) (529 [33.4%]), OPRA induction-like (induction FOLFOX/CAPOX followed by long-course chemoradiotherapy) (190 [12.0%]), OPRA consolidation-like (long-course chemoradiotherapy followed by consolidation FOLFOX/CAPOX) (257 [16.2%]), and other regimens (360 [22.7%]). After TNT, 192 (12.1%) underwent watch and wait, and 30 (1.9%) underwent local excision. Pathological or clinical complete response was reported in 23.2% of cases. At treatment failure, 8.5% was local and 16.4% was distant progression. Three-year event-free survival (EFS) was 68% (95% CI, 64%-71%), and 5-year overall survival (OS) was 79% (95% CI, 75%-83%). In the overall population, patients treated with the PRODIGE 23-like regimen were most likely to have serious adverse events (61 [23.5%]) but had better local control and survival outcomes than those treated with the RAPIDO-like (EFS: hazard ratio [HR], 0.68; 95% CI, 0.49-0.95; P = .03; OS: HR, 0.51; 95% CI, 0.27-0.97; P = .04), OPRA induction-like (EFS: HR, 0.66; 95% CI, 0.44-0.98; P = .04; OS: HR, 0.35; 95% CI, 0.18-0.70; P = .003), and OPRA consolidation-like (EFS: HR, 0.64; 95% CI, 0.44-0.93; P = .02; OS: HR, 0.50; 95% CI, 0.25-1.00; P = .05) regimens. In the matched population (928 patients [58.5%]), no differences in survival outcomes were observed between the TNT regimens. The findings of this case series study show substantial variation in the choice of the TNT regimen and were overall aligned with those reported in clinical trials, suggesting the efficacy of TNT in a clinical setting regardless of the specific regimen.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease globally. Current diagnostic methods, such as liver biopsies, are invasive and have limitations, highlighting the need for non-invasive alternatives. To investigate extracellular vesicles (EVs) as potential biomarkers for diagnosing and staging steatosis in patients with MASLD using machine learning (ML) and explainable artificial intelligence (XAI). In this single-center observational study, 798 patients with metabolic dysfunction were enrolled. Of these, 194 met the eligibility criteria, and 76 successfully completed all study procedures. Transient elastography was used for steatosis and fibrosis staging, and circulating plasma EV characteristics were analyzed through nanoparticle tracking. Twenty ML models were developed: Six to differentiate non-steatosis (S0) from steatosis (S1-S3); and fourteen to identify severe steatosis (S3). Models utilized EV features (size and concentration), clinical (advanced fibrosis and presence of type 2 diabetes mellitus), and anthropomorphic (sex, age, height, weight, body mass index) data. Their performance was assessed using receiver operating characteristic (ROC)-area under the curve (AUC), specificity, and sensitivity, while correlation and XAI analysis were also conducted. The CatBoost C1a model achieved an ROC-AUC of 0.71/0.86 (train/test) on average across ten random five-fold cross-validations, using EV features alone to distinguish S0 from S1-S3. The CatBoost C2h-21 model achieved an ROC-AUC of 0.81/1.00 (train/test) on average across ten random three-fold cross-validations, using engineered features including EVs, clinical features like diabetes and advanced fibrosis, and anthropomorphic data like body mass index and weight for identifying severe steatosis (S3). Key predictors included EV mean size and concentration. Correlation, XAI, and SHapley Additive exPlanations analysis revealed non-linear feature relationships with steatosis stages. The EV-based ML models demonstrated that the mean size and concentration of circulating plasma EVs constituted key predictors for distinguishing the absence of significant steatosis (S0) in patients with metabolic dysfunction, while the combination of EV, clinical, and anthropomorphic features improved the diagnostic accuracy for the identification of severe steatosis. The algorithmic approach using ML and XAI captured non-linear patterns between disease features and provided interpretable MASLD staging insights. However, further large multicenter studies, comparisons, and validation with histopathology and advanced imaging methods are needed.

To report on the efficacy and safety of elective switching from intravenously (IV) to subcutaneously (SC) administered Infliximab (IFX) in patients with immune mediated diseases. Retrospective analysis of patients with Crohn's disease (CD), Ulcerative Colitis (UC), Spondyloarthritis (SpA), Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) and chronic plaque Psoriasis (PsO) who were receiving IFX-IV for maintenance of remission in tertiary referral centers and were switched to IFX-SC based on their physician's choice. All patients with gastrointestinal and skin diseases were in clinical remission, while those with musculoskeletal disease had inactive disease or low disease activity. The primary endpoint was disease deterioration during a follow up period, of at least 6 months, according to disease specific composite measures. Between April 2023 and April 2024, a total of 344 patients (CD = 136, UC = 62, SpA = 52, PsA = 38, RA = 7, PsO = 44, co-existence of more than one disease = 5) were switched from IFX-IV to IFX-SC. After a mean±SD follow up period of 8 ± 4 months, 12 patients (3.5%) discontinued treatment with IFX-SC. Five of them (1.5%) because of disease worsening and the remaining 7 (2.0%) because of the occurrence of side effects. All 332 other patients (96.5%) showed favorable response, none of them requested an unscheduled visit, or developed an adverse event (clinical or laboratory) or needed escalation of treatment. Elective switching from IFX-IV to IFX-SC seems to be an effective and safe approach in real-world every day clinical practice to maintain long-term clinical remission, inactive disease or low disease activity in patients with immune-mediated diseases.