Search Results (83)

Background: Paediatric hepatocellular carcinoma (HCC), including its fibrolamellar variant (FLC), is a rare malignancy with distinct biological behaviour and limited therapeutic options. While complete surgical resection is a key determinant of survival, many patients present with unresectable tumours at diagnosis. The role of neoadjuvant chemotherapy in improving resectability, particularly in histologically distinct subtypes, remains inconclusive. Methods: We retrospectively analysed 43 patients (<18 years) with histologically confirmed conventional HCC (cHCC, n = 27) or FLC (n = 16) enrolled in the German Pediatric Liver Tumour Registry. We assessed clinical characteristics, treatment response, surgical outcomes, and survival. Special focus was placed on the impact of neoadjuvant chemotherapy in initially unresectable tumours. Results: FLC and cHCC exhibited significant differences in clinical presentation, such as age of presentation, AFP elevation, or presence of underlying liver disease. Although overall survival did not significantly differ between groups, cHCC tumours showed a markedly higher response to chemotherapy (62.5% partial remission vs. 0% in FLC). Complete resection (R0) was achieved in 77% of all patients and was the strongest predictor of survival. Importantly, a subset of cHCC patients who initially had unresectable tumours became eligible for curative surgery following neoadjuvant chemotherapy. Notably, delayed resection after chemotherapy led to outcomes comparable to those with upfront surgery, whereas progression during chemotherapy was associated with a universally poor prognosis. Conclusions: This study supports upfront resection as the preferred strategy in paediatric HCC and FLC whenever feasible. In cHCC, neoadjuvant chemotherapy demonstrated a favourable response profile and contributed to secondary resectability in a subset of initially unresectable cases, supporting a potential role within a multimodal treatment approach. In contrast, FLC showed limited responsiveness to current systemic therapies. These findings emphasise the importance of histology-specific strategies and highlight the ongoing need for more effective systemic options, particularly for unresectable FLC. Full article

Introduction: Total temporomandibular joint replacement (TMJR) is a well-established surgical solution for patients with severe TMJ disorders. It aims to relieve chronic pain, restore jaw mobility, and significantly enhance quality of life. This systematic review evaluates QoL outcomes following TMJR, analyzes complication profiles, compares custom versus stock prostheses, explores pediatric applications, and highlights technological innovations shaping the future of TMJ reconstruction. Methods: A systematic search of PubMed, Embase, and the Cochrane Library was conducted throughout April 2025 in accordance with PRISMA 2020 guidelines. Sixty-four studies were included, comprising 2387 patients. Results: Primary outcomes assessed were QoL improvement, pain reduction, and functional gains such as maximum interincisal opening (MIO). Secondary outcomes included complication rates and technological integration. TMJR consistently led to significant pain reduction (75–87%), average MIO increases of 26–36 mm, and measurable QoL improvements across physical, social, and psychological domains. Custom prostheses were particularly beneficial in anatomically complex or revision cases, while stock devices generally performed well for standard anatomical conditions. Pediatric TMJR demonstrated functional and airway benefits with no clear evidence of growth inhibition over short- to medium-term follow-up. Complications such as heterotopic ossification (~20%, reduced to <5% with fat grafting), infection (3–4.9%), and chronic postoperative pain (~20–30%) were reported but were largely preventable or manageable. Recent advancements, including CAD/CAM planning, 3D-printed prostheses, augmented-reality-assisted surgery, and biofilm-resistant materials, are enhancing personalization, precision, and implant longevity. Conclusions: TMJR is a safe and transformative treatment that consistently improves QoL in patients with end-stage TMJ disease. Future directions include long-term registry tracking, growth-accommodating prosthesis design, and biologically integrated smart implants. Full article

Objectives: We wished to evaluate the safety profile of the Janus kinase (JAK) inhibitors used in the Spanish population; to study the onset of major adverse cardiovascular events (MACEs) and thrombotic events (arterial and venous); and to analyze the factors associated with the onset of these events. Methods: We conducted a retrospective observational study of a cohort of patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA) included in the biological therapy registry of the Rheumatology Department of Virgen Macarena University Hospital (HUVM), Seville, Spain, who started targeted treatment between 2019 and late 2024. We collected data on disease activity, traditional cardiovascular risk factors, the Charlson comorbidity index, previous synthetic or biologic drug therapy, the use of corticosteroids (and their dose), severity data (structural damage, extra-articular manifestations), and adverse events at the end of follow-up (e.g., MACEs, infections, neoplasms, and herpes zoster). We performed a descriptive bivariate analysis and a multivariate logistic regression analysis (dependent variable: MACEs) to identify factors that were independently associated with MACEs. Results: The study population comprised 137 patients (110 with RA, 18 with PsA, and 9 with SpA) who were followed up for a mean of 3.9 (2.6) years. Most patients had received JAK inhibitors as their second-line or subsequent treatment. At the end of the follow-up, 82 patients (66.7%) continued their treatment. Nine patients (6.6%) experienced a MACE, and five experienced a heart attack. All of these patients had RA. We found no differences between JAK inhibitors in terms of the incidence of the adverse events studied. Patients who experienced MACEs were more often male and smokers (current or former) and more often had hypertension and diabetes. No significant differences were found in the association with disease activity or previous or concomitant treatment. The factors that were independently associated with MACEs were a previous cardiovascular event (OR, 10.74; 95%CI, 1.05–113.7; p = 0.036), male sex (OR, 9.7; 95%CI, 1.6–76.5; p = 0.016), diabetes mellitus (OR, 10.3; 95%CI, 1.75–83; p = 0.013), and the duration of treatment with JAK inhibitors (OR, 1.47; 95%CI, 1.13–2.01; p = 0.005). Conclusions: We found no differences in the onset of adverse events, specifically MACEs, between the different JAK inhibitors analyzed. These events are more common in patients who already have cardiovascular risk factors, such as diabetes mellitus, or who have already experienced a cardiovascular event. JAK inhibitors broadly suppress cytokines in patients whose disease is refractory to other treatments. However, we must continue to evaluate their long-term safety in real-world studies. Full article

Background: Thymic carcinoids are rare neuroendocrine tumors arising in the anterior mediastinum, often diagnosed at an advanced stage due to nonspecific clinical manifestations. Their management remains challenging because of the paucity of data, rarity of occurrence, and aggressive biological behavior compared to other well-differentiated neuroendocrine neoplasms. Methods: We conducted a comprehensive review of the current literature focusing on the classification, clinical presentation, diagnostics, treatment options, prognostic factors, and emerging experimental therapies for thymic carcinoids. Emphasis was placed on integrating recent molecular and therapeutic advances into clinical practice. Results: Surgical resection remains the cornerstone of treatment for localized disease, while systemic therapies such as everolimus, somatostatin analogs, platinum-based chemotherapy, and peptide receptor radionuclide therapy (PRRT) are options for advanced cases. Novel diagnostic modalities, including NETest, 64Cu-DOTATATE PET, and 18F-FDOPA PET, offer promise in early detection and disease monitoring. Molecular insights, particularly involving MEN1, ATRX, and DAXX mutations, pave the way for individualized targeted therapies. Immunotherapy and radioimmunotherapy represent emerging, albeit still experimental, approaches. Prognosis largely depends on tumor stage, differentiation, resectability, and functional activity, with a high recurrence rate necessitating prolonged surveillance. Conclusions: Thymic carcinoids pose significant diagnostic and therapeutic challenges. Advances in molecular profiling, novel imaging techniques, and systemic therapies offer hope for improved outcomes. Given the disease rarity, continued collaboration through registries and multicenter studies is essential to refine evidence-based management strategies. Full article

Background/Objectives: Psoriatic arthritis (PsA) is a chronic inflammatory condition that primarily affects the musculoskeletal system and skin. While biologic and targeted synthetic DMARDs have improved treatment, many patients still fail to achieve remission. Combining conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) with biologic (b) DMARDs or targeted synthetic (ts) DMARDs shows no added benefit over monotherapy with IL-17, IL-23 inhibitors, or JAK inhibitors, unlike TNFi, which benefit from csDMARD co-administration. Guselkumab (GUS) and risankizumab (RKZ) target IL-23 with high specificity. RCTs (DISCOVER 1 and 2, COSMOS) have confirmed GUS efficacy regardless of methotrexate (MTX) use, though liver toxicity was higher with MTX. Real-world data on GUS remain limited, with gaps in understanding its long-term effectiveness and drug survival. The aim of this study is to assess the following three points within a multicenter Italian real-life cohort of PsA patients treated with guselkumab (GUS) and followed for 12 months: (1) effectiveness and safety of GUS; (2) drug retention rate (DRR) and reasons for discontinuation; (3) impact of comorbidities on achieving minimal disease activity (MDA). Methods: This study utilized data from the GISEA registry, which includes centers in different parts of Italy (north, center, south, and islands), and included patients aged 18 and older diagnosed with PsA according to the CASPAR criteria. Results: Data on 170 PsA patients treated with GUS were collected. In the first 6 months, a prompt mean percentage improvement in all clinimetric indexes was observed compared to the baseline. At 6-month follow-up, ACR 20 was reached by 60% of patients, ACR 50 by 30%, ACR 70 by 15%, MDA by 28%, and DAPSA < 14 by 50% of patients in the overall group. Significant differences were found in the rate of ACR 50 in the bDMARD-naive group (50%) compared to one bDMARDs non-responder (NR) (8%) (p = 0.021). At 12-month follow-up, a notable gap was observed in the rate of patients reaching MDA between bDMARD-naive (60%) and one bDMARDs NR (22%) (p = 0.035) and between bDMARD-naive (60%) and ≥2 bDMARDs NRs (22%) (p = 0.024). By using multivariate binary logistic analysis, the predictors of reaching MDA at 12-month follow-up were naive bDMARDs (OR: 7.9, 95% CI: 1.3–44.8, p = 0.019) and a higher value of pGA at baseline (OR: 1.1, 95% CI: 1–1.5; p = 0.046). The presence of comorbidities, including fibromyalgia and obesity, did not seem to affect the reaching of MDA. At 12-month follow-up, the GUS retention rate was 76%, with a mean survival time of 10.5 months ± 0.2 (95% CI: 10–10.9). No significant differences in GUS survival time were found among bDMARD-naive, one bDMARDs NR, and ≥2 bDMARDs NR patients (in the latter, regardless of the previous mechanism of action: TNFi or other mechanism), as well as between patients treated with GUS in monotherapy and those treated in combination with csDMARDs. A low rate (17%) of discontinuation was found due to both primary NR and secondary NR. The high safety of GUS was recorded. In fact, discontinuation due to adverse events (all definable as minor) was observed in just 4% of patients. By using COX regression multivariate analysis, the factors associated with higher GUS discontinuation risk were a more severe baseline PASI (HR: 1.05, 95% CI: 1–1.1, p = 0.038) and higher baseline ESR (HR:1.06, 95% CI: 1–1.03, p = 0.05). Conclusions: Good performance of GUS was observed in both biologic-naive patients and those with failure of previous bDMARDs (regardless of the mechanism of action of the previous drug: TNFi or non-TNFi), presenting good persistence in therapy even when used as a third mechanism of action. Its high safety profile allows the use of GUS even in particularly complex patients. Full article

Introduction: Among aortic diseases in children, congenital defects such as coarctation of the aorta (CoA), interrupted aortic arch (IAA), hypoplastic aortic arch (HAA), and hypoplastic left heart syndrome (HLHS) predominate. Tissue patches are applied in pediatric cardiovascular surgery for the repair of congenital aortic defects as a filling material to replenish missing tissue or as a substitute material for the complete reconstruction of the vascular wall along the course of the vessel. This retrospective single-center study aimed to present the safety and feasibility of extracellular matrix (ECM) biological scaffolds in pediatric aortic surgery. Patients and methods: There were 26 patients (17 newborns and nine children), who underwent surgical procedures in the Department of Pediatric Cardiac Surgery (Poznań, Poland) between 2023 and 2024. The patients’ population was divided into two subgroups according to the hemodynamic nature of the primary diagnosis of the congenital heart defect and the performed pediatric cardiovascular surgery. The first group included 18 (72%) patients after aortic arch repair for interrupted aortic arch and/or hypoplastic aortic arch, while the second group included seven (28%) patients after aortopulmonary anastomosis. In the first group, patches were used to reconstruct the aortic arch by forming an artificial arch with three separate patches sewn together, primarily addressing the hypoplastic or interrupted segments. In the second group, patches were applied to augment the anastomosis site between the pulmonary trunk and the aortic arch, specifically at the connection points in procedures, such as the Damus–Kaye–Stansel or Norwood procedures. The analysis was based on data acquired from the national cardiac surgery registry. Results: The overall mortality in the presented group was 15%. All procedures were performed using median sternotomy with a cardiopulmonary bypass. The cardiopulmonary bypass (CPB) and aortic cross-clamp (AoX) median times were 144 (107–176) and 53 (33–79) min, respectively. There were two (8%) cases performed in deep hypothermic circulatory arrest (DHCA). The median postoperative stay in the intensive care unit (ICU) was 284 (208–542) h. The median mechanical ventilation time was 226 (103–344) h, including 31% requiring prolonged mechanical ventilation support. Postoperative acute kidney failure requiring hemodiafiltration (HDF) was noticed in 12% of cases. Follow-up data, collected via routine transthoracic echocardiography (TTE) and clinical assessments over a median of 418 (242.3–596.3) days, showed no evidence of patch-related complications such as restenosis, aneurysmal dilation, or calcification in surviving patients. One patient required reintervention on the same day due to a significantly narrow ascending aorta, unrelated to patch failure. No histological data from explanted patches were available, as no patches were removed during the study period. The median (Q1–Q3) hospitalization time was 21 (16–43) days. Conclusions: ProxiCor^® biological patches derived from the extracellular matrix can be safely used in pediatric patients with congenital aortic arch disease. Long-term follow-up is necessary to confirm the durability and growth potential of these patches, particularly regarding their resistance to calcification and dilation. Full article

Background/Objectives: Inflammatory bowel diseases (IBDs) comprise a group of chronic idiopathic disorders, including ulcerative colitis (UC), Crohn’s disease (CD), and indeterminate colitis (IC). Complex genetic factors, in addition to environmental triggers, have been shown to play a fundamental role in the pathogenesis of IBD, contributing to disease susceptibility. The transition of adolescents with inflammatory bowel disease (IBD) to adult care represents a significant challenge for patients, their families, and healthcare providers. Approximately 25% of individuals with IBD receive a diagnosis before the age of 16, and this population is at increased risk for adverse clinical outcomes. As a result, the transition of care has garnered substantial attention in the scientific and clinical communities over the past decade. This study aims to analyze a cohort of pediatric Sardinian patients with IBD to assess clinical characteristics at diagnosis and at the time of transition and determine potential correlations between NOD2/CARD15 gene variants and HLA class II with the disease phenotype. Methods: From January 2014 to August 2024, we performed an observational, cross-sectional study that included pediatric patients with IBD enrolled in the only pediatric IBD reference center in Sardinia. Data were obtained from the patients’ medical records and from a questionnaire administered at the inclusion visit. In addition, we genotyped a portion of our cohort for the Leu1007fsinsC (SNP13), Gly908Arg (SNP12), and Arg702Trp (SNP8) variants of the NOD2/CARD15 gene, as well as for HLA-DRB1, -DQA1, and -DQB1 class II genes. The obtained results were compared with pediatric data from the national epidemiological IBD registry and existing literature. Results: Seventy-one IBD patients were enrolled (UC 43, CD 28, M 34, F 37). Median age at diagnosis was 12.2 years (IQR 2–17). After a median disease duration of 5 years (IQR: 1–16), only three UC patients experienced proximal extension of proctitis or left-sided colitis, and no CD patients experienced new localizations of disease. Fifteen patients developed extraintestinal manifestations. No significant difference was found in median diagnostic delay (DD) between UC [4 months (IQR: 1–84)] and CD patients [4.5 months (IQR: 1–48)]. At the transition visit, overall, twenty-nine patients (42%) were exposed to one biologic agent (vs. 3% at baseline; p < 0.02); 3 patients (4%) were exposed to two or more biologic agents. 7% of patients (5/71) underwent surgery. By comparing the distribution of NOD2/CARD15 SNPs between pediatric patients and an adult CD population, we found a significant association between gene allelic variants and pediatric onset (p = 0.00048). Our study also revealed a statistically significant association between Sardinian pediatric patients carrying NOD2/CARD15 mutations and early-onset CD (p < 0.009492), along with a stenosing phenotype (p < 0.024) and increased surgical risk (p < 0.026). No significant associations were observed between HLA class II alleles and IBD in our population. Conclusions: Our results provide important insights into the clinical and epidemiological features of the pediatric IBD population. In addition, our study highlights the significant role of NOD2/CARD15 gene polymorphisms in pediatric onset CD. These variants influence the age of onset and disease phenotype, characterized by greater severity and a higher risk of surgical intervention in pediatric patients. Full article

Total Hip Arthroplasty (THA) is a widely used surgical procedure to restore mobility and reduce pain in patients with hip joint disorders. Implant success and longevity are influenced by the selection of appropriate materials. This study presents a comprehensive literature review based on structured searches in Scopus and Web of Science, focusing on material selection criteria and methods in THA. The inclusion criteria targeted original studies and reviews addressing material properties, selection techniques, and clinical performance. A bibliometric analysis and keyword co-occurrence network were used to highlight major research themes. The review examines traditional materials such as Metal-on-Polyethylene (MoP), as well as advanced options like ceramics, composites, and Functionally Graded Materials (FGMs). Key challenges discussed include aseptic loosening, wear resistance, and stress shielding. Selection methodologies such as Multi-Criteria Decision-Making (MCDM), Weighted Properties Methods (WPM), and computational tools like Ashby charts and CES Selector are analyzed. The findings from international arthroplasty registries show that more than half of implant failures are linked to material-related factors. This study therefore aims to guide material selection processes in THA by aligning clinical performance with biomechanical and biological requirements, supporting improved implant outcomes and long-term surgical success. Future developments should focus on patient-specific solutions and continuous innovation. Full article

Background: Pediatric-onset familial inflammatory bowel disease (IBD) may differ from sporadic pediatric-onset IBD in its genetic and environmental background and may have distinct clinical and therapeutic implications. Objective: To evaluate the influence of a positive family history of IBD on the use of medical therapies and surgical interventions in adult patients with pediatric-onset IBD. Methods: Retrospective case–control study using the Spanish ENEIDA registry, including adults diagnosed with pediatric-onset IBD since 2006. Familial forms (FFs) (defined by a first-degree relative with IBD) and sporadic forms (SF) (with no relatives of any grade with IBD) were matched 1:4 by type of IBD, sex, age at IBD diagnosis, disease location, disease pattern, development of perianal disease and smoking status at diagnosis. The study outcomes were the use of immunomodulators, biological therapies, intestinal surgery, and perianal surgery during follow-up. Results: Six-hundred and fifty-five Crohn’s disease (CD) (131 FF) and 440 ulcerative colitis (UC) (88 FF) patients were included. Immunomodulators, biological therapy, and intestinal surgery were used evenly among FF and SF patients for both UC and CD. However, a higher requirement for perianal surgery among FF-CD patients (18.3% vs. 10.5%, p = 0.014), together with a shorter time to perianal surgery (11 vs. 20 months, log-rank p = 0.004), was observed. Conclusions: Patients with FF of pediatric-onset IBD do not exhibit an increased use of immunomodulators, biological agents, or intestinal surgery, but do exhibit a higher need for perianal surgery, as compared to patients with SF pediatric-onset IBD. Full article

Background: Breast cancer is a complex and heterogeneous disease characterized by distinct molecular subtypes with varying prognoses and treatment responses. Multiple factors influence breast cancer outcomes including tumor biology, patient characteristics, and treatment modalities. Demographic factors such as age, race/ethnicity, menopausal status, and body mass index have been correlated with variations in incidence, mortality, and survival rates. Over the past decade, comprehensive genomic profiling has been widely used to identify molecular biomarkers and signatures to develop novel therapeutic strategies for patients. For instance, the FLEX registry (NCT03053193) enrolled stage I–III breast cancer patients across 90 institutions in the United States and stratified risk groups based on a 70-gene signature (MammaPrint^®-MP) and molecular subtype based on an 80-gene signature (BluePrint^®-BP). This study aimed to identify the gene expression patterns and biomarkers associated with breast cancer risk and progression by integrating transcriptomic and clinical data. Methods: Targeted 111 unique gene expression and clinical data points from 978 breast cancer samples, representing each BP subtype (26% Luminal A, 26% Luminal B, 25% Basal, 23% HER2), obtained from Agendia Inc. These genes were selected based on their involvement in the mercapturic acid pathway, white and brown adipose tissue markers, inflammation markers, tumor-associated genes, apoptosis, autophagy, and ER stress markers. All statistical analyses, including principal component analysis (PCA), were performed using R version [4.4.0]. Prognostic values and genetic alterations were investigated using various web-based programs as described in the Methods section. Results: PCA of gene expression data revealed distinct clustering patterns associated with risk categories and molecular subtypes, particularly with principal component 4 (PC4). Genes related to oxidative stress, autophagy, apoptosis, and histone modification showed altered expression across risk categories and molecular subtypes. Key differentially expressed genes included SOD2, KLK5, KLK7, IL8, GSTM1/2, GLI1, CBS, and IGF1. Pathway analysis highlighted the enrichment of processes related to autophagy, cellular stress response, apoptosis, glutathione metabolism, deacetylation, and oxidative stress in high-risk and basal-like tumors compared with Ultralow and Luminal A tumors, respectively. Conclusions: This study identified gene expression signatures associated with breast cancer risk and molecular subtypes. These findings provide insights into the biological processes that may drive breast cancer progression and could inform the development of prognostic biomarkers and personalized therapeutic strategies. Full article

Background: Hypereosinophilic syndrome (HES) is a heterogeneous group of rare disorders defined by the presence of marked eosinophilia resulting in end organ damage. The diagnostic approach is multidisciplinary and treatment goals include reductions in flares and eosinophils with minimal drug-related side effects. Results: Eleven patients (n = 11) with a diagnosis of idiopathic HES were included in the study [M/F: 6/5, median age: 54 (95% CI: 38.2 to 68.5), smokers/never smokers: 5/6]. Asthma was present in the majority of them (n = 8, 72.7%); four patients (n = 4, 36.4%) presented with eosinophilic pleural effusions, two patients (n = 2, 18.2%) with cardiac arrhythmias, and one with bilateral eyelid angioedema. Eight patients (72.7%) were treated with mepolizumab (300 mg/month) and three (27.3%) with benralizumab (30 mg/4 weeks). The median values of eosinophils at baseline and 12 months after initiation of biologic agent were 3000 (95% CI: 2172 to 11,365) K/μL and 50 (95% CI: 3 to 190) K/μL, respectively, p = 0.0002. All patients with concomitant asthma (n = 8) experienced elimination of asthma flares, asthma control (ACQ < 0.75), functional improvement (mean ΔFEV1: 857 ± 594 mL), and an 82% reduction in oral corticosteroids, p = 0.0001. Materials and Methods: Patients with highly characterized idiopathic HES treated with anti-eosinophilic agents between 1 October 2019 and 1 October 2023 were retrospectively included in the study. The aim of this study was to present clinical, laboratory, and functional features and outcomes in patients with thoroughly investigated idiopathic HES treated with biologic agents targeting eosinophils. Conclusions: Biologic agents in patients with idiopathic HES—following thorough diagnostic investigation—are both safe and effective, sparing the toxicity of immunosuppressive agents. Real-life data from larger registries are greatly anticipated. Full article

Tendon defect is one of the common clinical diseases related to the growing population mean age and the number of athletes. Due to an increasing demand for tendon repair surgical interventions, several tendon augmentation products, capable of guaranteeing the necessary biological and visco-elasticity properties and mechanical support, have been developed. In this regard, commercially available products may be grouped into three main categories: (i) natural, (ii) synthetic, and (iii) hybrid biomaterial-based products. Firstly, to better define the research area of this work, common search engines were employed to acquire information from reports or website portfolios of important competitors in the global tendon repair market. Secondly, public registries and bibliographic databases were also employed to analyse data from registered clinical trials and published clinical studies performed to evaluate the safety and efficacy of each product. Ten new products have been launched on the market in the last fifteen years: advantages, disadvantages, and future perspectives regarding their use for tendon augmentation treatment are discussed. Although hybrid biomaterial-based products may be considered as more oriented to the new frontiers of tendon augmentation technology, future improvements, especially focused on both mechanical properties and biocompatibility, are needed. However, scientific innovations must navigate convoluted clinical regulatory paths, which, due to high costs for investors, long development timelines, and funding shortages, hinder the translation of many scientific discoveries into routine clinical practice. Full article

Background: Biosimilars represent a fundamental advancement in global healthcare, offering significant cost containment while maintaining both therapeutic efficacy and safety in the management of chronic diseases. The cost savings generated by adopting biosimilars could be reinvested to foster innovation in the healthcare sector and enhance patient access to advanced therapies. Methods: A comprehensive analysis was conducted within an Italian healthcare organization which, through its hospital network, serves over 3.5 million individuals. Usage patterns, expenditure, and patient coverage for the principal biosimilar agents across various therapeutic areas were examined. Data were extracted from institutional registries, and a year-over-year comparison from 2022 to 2024 was performed to evaluate trends in consumption, biosimilar adoption among treatment-naïve patients, incurred costs, potential and actual savings, as well as therapeutic switching profiles. Results: The analysis revealed a marked shift towards biosimilar formulations for the majority of the evaluated biological agents between 2022 and 2024. However, for certain active substances, a reduced market penetration of biosimilars was observed, and critical issues persist that will necessitate future interventions. Conclusions: The results demonstrate a consistent upward trajectory in biosimilar adoption, underscoring significant progress toward their integration into routine clinical practice—a transition that has generated substantial savings over the three-year period considered. Assuming a complete transition to biosimilars, the cumulative potential savings over the three-year period would amount to EUR 7,172,372.99 in 2022, EUR 6,209,289.05 in 2023, and EUR 23,536,824.05 in 2024. This trend aligns with strategic objectives to enhance the sustainability of the Italian National Health Service (SSN) through optimized resource allocation and improved patient access. Full article

Background: Real-world data on currently used biologic agents in patients with severe asthma are lacking. Methods: In this retrospective study, we recorded between 16 May 2020 and 31 December 2024 consecutive patients who presented to our asthma outpatient clinic received a diagnosis of uncontrolled severe asthma and were treated with biologic agents. Outcomes included a comparison of disease phenotypic characteristics, as well as asthma control, lung function, longitudinal use of corticosteroids, and hospitalizations due to exacerbations at baseline and post-biologic treatment at 6-month follow-up. Results: We identified 80 patients with uncontrolled severe asthma treated with biologic agents. The median age (95% CI) at the time of diagnosis was 67.0 (61.0 to 70.0) years. Most patients were female (65.0%, n = 52) and never smokers (51.3%, n = 41). The median value of ACT (95% CI) was 15 (15 to 16) at the time of diagnosis. The mean FEV₁% predicted ±SD at the baseline was 68.9 ± 22.0. The median value of blood eosinophils (95% CI) was 365 (252 to 448) K/μL in the overall population. One-third (36.3%) of patients were hospitalized due to severe asthma exacerbation in the previous year. Longitudinal use of oral corticosteroids was recorded in 11.3% of included patients. Three patients (3.8%) were treated with omalizumab, 23 patients (28.8%) with mepolizumab, 33 patients (41.2%) with benralizumab and 21 patients (26.2%) with tezepelumab. The median value of ACT (95% CI) post-biologic treatment at 6-month follow-up was 20 (20 to 21), p < 0.0001. The mean FEV₁% predicted ±SD at 6-month follow-up was 77.6 ± 25.2, p = 0.12. The median value of blood eosinophils (95% CI) 6 months after initiation of biologic treatment was 100 (40 to 121) K/μL, p < 0.0001. Elimination of hospitalizations due to asthma flares was recorded in 97.5% of patients (p < 0.0001). With regard to the longitudinal use of oral corticosteroids, we noticed that 96.2% of patients achieved discontinuation. No treatment-related adverse events were noticed. Conclusions: The administration of current biologic agents in patients with severe asthma seems to be both effective and safe, sparing the toxicity of oral corticosteroids. Full article

Background and Objectives: Coronavirus disease-2019 (COVID-19) posed unique challenges worldwide, underscoring important gaps in healthcare preparedness for patients receiving immunosuppressive therapies, such as the individuals with axial spondyloarthritis (axSpA), a subgroup of spondyloarthritis (SpA) characterized by chronic inflammation and immune dysregulation. While global registry data exist for SpA, specific data on axSpA alone remain scarce, especially in Central and Eastern European populations. This study aims to identify predictive factors for severe COVID-19 outcomes and provide a descriptive analysis of axSpA patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), using real-world data from the Romanian Registry of Rheumatic Diseases (RRBR). Materials and Methods: This is a three-year retrospective observational cohort study that included 5.786 axSpA patients from the RRBR, of whom 183 (3.16%) were diagnosed with SARS-CoV-2 infection. Data were analyzed using R V4.4.1 and performing univariate and multivariate binary logistic regression to estimate associations using odds ratios (ORs), 95% confidence intervals (CIs), and p-values. A backward selection algorithm was applied to create the final predictive model, accounting for multicollinearity through variance inflation factors (VIFs). Results: The mean age of patients was 48.19 ± 12.26 years, with male predominance (64.5%). Serious COVID-19 (encompassing moderate to critical cases) occurred in 46 cases, with age ≥ 52.5 years (OR 2.64, 95% CI: 1.28–5.48, p = 0.009) and arterial hypertension (OR 2.57, 95% CI: 1.29–5.16, p = 0.007) identified as significant predictors. Individuals with advanced education levels had nearly three times lower odds of experiencing serious COVID-19 (OR 0.38, 95% CI: 0.18–0.76, p = 0.008). Furthermore, our findings confirm the lack of association between HLA-B27 and COVID-19 severity (p = 0.194), contributing to the ongoing discussion regarding its potential immunological role. Moreover, irrespective of the biological therapy administered, the likelihood of experiencing serious SARS-CoV-2 outcomes was not statistically significant (p = 0.882). In the final predictive model, only older age and higher education were deemed as predictive factors. Conclusions: This study highlights key predictors of COVID-19 severity in axSpA patients and emphasizes the protective role of higher education, an underexplored determinant of health outcomes in inflammatory diseases. The lessons learned during these last years can shape a more informed and compassionate healthcare system. Full article