Search Results (2,861)

This narrative review examines topical anti-inflammatory therapies in veterinary medicine through the lens of the One Health framework, integrating pharmacology, dermatology, ecotoxicology, food safety, and regulatory science. It discusses the interconnected roles of veterinarians, pharmacists, environmental scientists, public health authorities, and regulatory bodies in addressing antimicrobial resistance, environmental contamination, zoonotic transmission, and drug residues in food-producing animals. By emphasising cross-sector collaboration, the review highlights how coordinated strategies can enhance animal welfare, safeguard human health, and reduce ecological burden. The article analyses inflammatory conditions in companion and farm animals and compares systemic versus topical anti-inflammatory approaches. Particular attention is given to corticosteroids, NSAIDs, immunomodulators, pro-resolving lipid mediators, and plant-derived bioactives, alongside advances in vehicles such as lipid nanocarriers and biodegradable film-forming systems designed to minimise systemic absorption and environmental dispersion. Regulatory considerations, residue control, pharmacovigilance gaps, and sustainability-oriented formulation strategies are critically addressed. Topical anti-inflammatory therapies, when rationally designed and monitored under One Health principles, represent a strategic opportunity to improve therapeutic precision while limiting systemic toxicity and ecological impact. Future directions should prioritise translational research, eco-compatible formulation design, and harmonised regulatory frameworks. Full article

The increasing consumption of pharmaceuticals associated with global population growth has intensified concerns regarding their release into aquatic environments and potential ecotoxicological effects. In this context, this study evaluated the ecotoxicity and biodegradation of the widely used corticosteroid prednisone. Ecotoxicity assays were performed using aquatic organisms representing different trophic levels: Artemia salina (microcrustacean), Aliivibrio fischeri (marine bacterium), and the cyanobacterium Microcystis novacekii. Biodegradation assays were conducted using M. novacekii. Prednisone was tested at concentrations ranging from 5 to 100 mg/L, corresponding to its maximum solubility in water. All experiments were carried out in accordance with standardized protocols (ABNT NBR 16530, ABNT NBR 15411-3, ISO 11348-3, and OECD 201). No toxic effects were observed for prednisone in any of the tested organisms, as responses at all tested concentrations, including the highest, were not significantly different from the control. Therefore, it was not possible to estimate EC50 values within the tested concentration range. According to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS), substances with effect concentrations above 100 mg/L are considered non-toxic to aquatic organisms. During biodegradation assays, a reduction in prednisone concentration was observed during the growth of M. novacekii, which was associated with an increase in the pH of the culture medium. These results suggest that prednisone degradation occurred indirectly through pH changes caused by cyanobacterial growth rather than through direct metabolic pathways. Full article

Background/Objectives: Pericardial effusion (PEf) is a frequent finding after cardiac surgery. Progression to cardiac tamponade (CT) is a rare but life-threatening complication. Current evidence remains limited due to insufficient data on prevalence, progression predictors and management strategies. Methods: We retrospectively analyzed anamnestic, clinical, laboratory, echocardiographic and therapeutic data from 2662 patients (74 ± 11 years) admitted to the Cardiac Rehabilitation ward between 2022 and 2024. Results: Among 2152 (81%) cardiac surgery patients, 382 (18%) developed PEf: 58% mild, 38% moderate, and 4% severe. Patients developing PEf tended to be younger and more frequently male. In addition, PEf development was seen more commonly after aortic and combined surgeries. All patients with severe PEf or CT had undergone surgery via sternotomy, whereas minithoracotomy was inversely associated with PEf severity. Postoperative complications occurred in 92% of PEf patients, mainly due to arrhythmia, hemodynamic deterioration, or heart failure. Overall outcome was favourable in 98% of patients. CT occurred in eight patients (2%). Anticoagulation therapy was more frequent among patients who developed PEf or CT. Preventive colchicine was prescribed in only 16% of cases. No PEf-specific therapy was administered in 56% of PEf patients, while corticosteroids and nonsteroidal anti-inflammatory drugs were used in 28% and 8% of cases, respectively, without surgical wound complications. No PEf recurrences were observed during follow up (517 ± 424 days). Conclusions: PEf is a common complication after cardiac surgery, more frequently in young males, usually of mild or moderate severity. The majority of these cases resolve using either a conservative or pharmacological approach, predominantly via corticosteroids. Patients undergoing aortic surgery, experiencing postoperative complications (especially arrhythmias), and receiving anticoagulation therapy were associated with severe PEf or CT. Despite guideline recommendations, colchicine remains markedly underutilized. Full article

Background: Influenza is a common cause of hospitalization in young children, particularly infants. While most infections are self-limited, severe and life-threatening complications may occur. Diffuse alveolar hemorrhage (DAH) is a rare pulmonary manifestation of influenza, predominantly reported in adults, and is exceedingly uncommon in immunocompetent infants. Case Presentation: We report the case of an 8-month-old previously healthy female infant who presented with influenza A infection and rapidly progressed to acute respiratory failure and shock despite antiviral therapy. Bleeding was noted from the nasal cavity prior to clinical deterioration, and during emergent endotracheal intubation, blood was observed flooding the bronchial tree, consistent with massive pulmonary hemorrhage. Flexible bronchoscopy showed diffusely erythematous and friable airway mucosa without an identifiable focal bleeding source, and early bronchoalveolar lavage was nondiagnostic. Nasopharyngeal testing confirmed influenza A (H3). Laboratory findings revealed severe systemic inflammation, leukopenia with neutropenia, and anemia with normal coagulation parameters. Chest imaging demonstrated bilateral pulmonary infiltrates. After exclusion of autoimmune, coagulation, immunodeficiency, and alternative infectious causes, a diagnosis of diffuse alveolar hemorrhage secondary to influenza A infection was established. The patient was successfully managed with supportive care, antiviral therapy, tranexamic acid, and empiric antibiotics, without corticosteroid treatment, and made a full recovery. Conclusions: This case emphasizes that influenza-associated DAH in infants may occur without overt hemoptysis and may not demonstrate classical BAL findings early in the disease course. Clinicians should maintain a high index of suspicion in rapidly deteriorating infants with influenza and diffuse pulmonary infiltrates. The optimal role of corticosteroids remains uncertain and should be individualized. Full article

Background: Infantile hepatic hemangiomas (IHH) are common benign vascular tumors in infancy with diverse presentations. Methods: We report a 7-week-old infant presenting with hepatosplenomegaly, multiple skin and hepatic hemangiomas, anemia, and recurrent lung infections. Results: Treatment included propranolol, corticosteroids, and sirolimus, along with antifungal prophylaxis with fluconazole. The patient developed pneumothorax and pulmonary aspergillosis. Despite antifungal therapy with voriconazole and liposomal amphotericin B, along with surgical intervention, her condition deteriorated, resulting in multi-organ failure and death at 8.5 months of age. Conclusions: This case illustrates the complexity of IHH management and highlights the risk of severe infections during immunosuppressive therapy even when standard prophylaxis protocols are applied. Full article

Background/Objectives: Given the narrow therapeutic range of tacrolimus and substantial inter-individual variability in trough levels, both total daily dose and the trough level-to-dose ratio are commonly used to guide dose optimization. In this study, Life-Cycle Pharma tacrolimus was compared with immediate-release tacrolimus in a real-world setting. Methods: This longitudinal observational study included kidney transplant recipients at two Hungarian university clinics. Sixty-three (63) patients completed the study and were included in the statistical analysis. They received either Life-Cycle Pharma-tacrolimus (n = 40) or immediate-release tacrolimus (n = 23) as maintenance therapy in the two study arms, each combined with everolimus or mycophenolic acid and corticosteroids. Patients were enrolled 4–6 weeks after transplantation and prospectively followed for 48 months. Tacrolimus trough level, total daily dose and their ratio were recorded at each of the seven follow-up visits during the 48-month study period. Epidemiological data, patient characteristics, laboratory parameters (including eGFR, de novo donor-specific antibodies, and CMV and BK virus incidence), and acute rejection episodes were monitored. Results: The mean age at enrolment was 53.35 years, and 41 patients (65.08%) were male. A stable therapeutic maintenance trough level was achieved in both study arms. Life-Cycle Pharma tacrolimus required a 30% lower total daily dose than immediate-release tacrolimus to achieve comparable exposure. A gradual decline in eGFR was observed in the immediate-release tacrolimus arm (a mean decrease of 6.06 mL/min/1.73 m² over 4 years) from a baseline level of 58.52 mL/min/1.73 m² (±16.69), whereas GFR increased in the Life-Cycle Pharma tacrolimus arm (a mean increase of 4.76 mL/min/1.73 m² over the same period) from a significantly lower baseline level of 46.55 mL/min/1.73 m² (±17.04). Conclusions: Both formulations provided effective long-term maintenance immunosuppression in kidney transplant recipients and maintained stable trough levels. Life-Cycle Pharma tacrolimus represents a potential option for dose minimization, and it also helped to stabilize renal function despite the worse baseline condition. Full article

Alcohol-associated Hepatitis (AH) is a rare acute injury caused by alcohol consumption, which can lead to one of the most severe manifestations of liver disease. It is part of the alcohol-related liver diseases (ArLD) spectrum, which represents a major global health burden, with oxidative stress and inflammation serving as central, interconnected pathogenic mechanisms. Chronic alcohol (ethanol) consumption induces hepatic reactive oxygen species (ROS) generation through multiple pathways, including cytochrome P450 2E1 (CYP2E1) induction, mitochondrial dysfunction, and NADPH oxidase activation. These oxidative insults trigger a cascade of cellular damage encompassing lipid peroxidation, protein adduct formation, DNA damage, and endoplasmic reticulum stress, ultimately leading to hepatocyte dysfunction and multiple forms of cell death, including apoptosis, necroptosis, pyroptosis, and ferroptosis. The inflammatory response, orchestrated primarily by Kupffer cells and infiltrating neutrophils through Toll-like receptor (TLR) signalling and inflammasome activation, not only amplifies hepatic injury but also promotes fibrogenesis through hepatic stellate cell activation. Neutrophils, characterised by elevated lipocalin-2 expression and spontaneous NETosis in AH, exhibit a paradoxical role by driving both tissue damage and repair. Current therapeutic strategies include corticosteroids, which remain the first-line treatment for severe AH, while emerging therapies targeting the gut–liver axis, hepatic regeneration, and specific molecular targets show promise in clinical trials. This review comprehensively examines the molecular crosstalk between oxidative stress and inflammation in the pathogenesis of AH to highlight current and investigational therapeutic approaches targeting these interconnected pathways. Full article

Background/Objectives: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammatory disease frequently associated with recurrence after endoscopic sinus surgery (ESS). Although biologic therapies such as dupilumab have demonstrated efficacy in severe CRSwNP, the optimal timing of treatment initiation in relation to surgery remains unclear. This study aimed to evaluate the clinical outcomes of early postoperative initiation of dupilumab after revision ESS using a multidimensional assessment of disease control. Methods: This retrospective observational study included adult patients with severe CRSwNP treated with dupilumab at a tertiary referral centre. All patients had undergone at least two previous ESS procedures and initiated dupilumab within 30 days following revision surgery. Clinical outcomes were assessed at baseline and after 12 months, including Nasal Polyp Score (NPS), Sinonasal Outcome Test-22 (SNOT-22), nasal congestion and olfactory visual analogue scale (VAS) scores, and asthma control in patients with comorbid asthma. Treatment response was evaluated using a multidomain assessment. Results: Ten patients were included. After 12 months, significant improvements were observed in NPS (from 4.7 ± 2.3 to 0.4 ± 1.0; p = 0.0019) and SNOT-22 (from 61.9 ± 17.3 to 26.5 ± 14.7; p = 0.0019). Nasal congestion and olfactory VAS scores also improved significantly. Most patients (70%) achieved an excellent multidimensional response, while 30% showed a moderate response. No patients required systemic corticosteroids or revision surgery during follow-up. Conclusions: Early postoperative initiation of dupilumab after revision ESS was associated with improvements in endoscopic findings, symptom severity, and quality of life. These findings suggest that the early postoperative period may represent a therapeutic window in selected patients with severe recurrent CRSwNP. However, results should be interpreted with caution and considered hypothesis-generating. Full article

Background/Objectives: Patients with inflammatory bowel disease (IBD) have an increased fracture risk, but whether femur fracture risk differs from that of the general population remains unclear. We compared the risks of overall femur fractures and femur fractures requiring surgery in patients with IBD versus matched controls, and evaluated the association between corticosteroid exposure and femur fracture risk in IBD. Methods: Using the Korean National Health Insurance Service database, we identified patients newly diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC) between 2008 and 2018. After 1:3 matching by age and sex, 33,778 patients with IBD (24,370 UC and 9408 CD) and 101,265 non-IBD controls were included. Incidence of femur fractures (overall and requiring surgery) was compared between groups. Multivariable analyses were performed to assess risk factors, including age, sex, disease subtype, comorbidity burden, and corticosteroid use duration. Results: Compared with controls, CD was associated with a higher incidence of femur fracture (HR, 2.10; 95% CI, 1.61–2.74; p < 0.001), whereas UC showed no clear association (HR, 1.15; 95% CI, 0.96–1.38; p = 0.120). In multivariable analysis, CD remained independently associated with femur fracture (HR, 1.74; 95% CI, 1.33–2.29; p < 0.001), while UC did not (HR, 0.99; 95% CI, 0.82–1.19; p = 0.890). Femur fractures requiring surgery were more frequent in both UC (HR, 1.35; 95% CI, 1.09–1.69; p = 0.028) and CD (HR, 1.67; 95% CI, 1.20–2.33; p = 0.003). Older age, female sex, higher comorbidity index, and longer corticosteroid exposure were associated with femur fracture in IBD. Conclusions: Only CD was associated with increased overall femur fracture risk; however, both CD and UC were associated with a higher risk of surgically treated femur fractures. Strategies to optimize bone health and minimize corticosteroid exposure may reduce femoral fracture risk in IBD. Full article

Background and Objectives: Hemodialysis (HD) patients represented a highly vulnerable population during the COVID-19 pandemic, both clinically and psychologically. Data regarding acute anxiety requiring pharmacologic treatment in this setting are limited. The aim of the study was to assess factors influencing clinical evolution, psycho-emotional disturbances reflected by “de novo” anxiolytic use, and vital prognosis of hospitalized COVID-19 patients on HD. Materials and Methods: The study included 211 patients followed between 2020 and 2023 (149 were COVID-19 positive and 80 required hospitalization) and comprised two sequential phases: an in-hospital phase during COVID-19, in which disease severity factors, in-hospital mortality, and the requirement for de novo anxiolytic therapy were assessed, and a follow-up phase, which evaluated overall mortality and the impact of vaccination on long-term outcomes. Results. Hospitalized patients were older, had lower dialysis adequacy, and a lower rate of COVID-19 vaccination. Severe COVID-19, associated with elevated inflammatory markers, prolonged hospitalization, and an increased need for anxiolytic therapy to control acute psychopathological disturbances, was significantly more frequent in patients with underlying oncological comorbidities. Patients who died from COVID-19 during hospitalization were older (69.364 ± 1.973 vs. 66.426 ± 1.546, p = 0.239), predominantly male (66.69% vs. 48.93%, p = 0.064), had similar BMI (26.836 ± 1.120 vs. 26.909 ± 0.943, p = 0.961), and had shorter duration on HD (5.182 ± 4.733 vs. 7.383 ± 6.060, p = 0.085). Patients who received anxiolytic therapy during hospitalization for COVID-19 were younger, predominantly male, and had a longer dialysis vintage as well as a higher body mass index. Although the de novo need for anxiolytics during COVID hospitalization was associated with multiple parameters in the linear regression analysis, the multivariable regression model showed a significant and strong association only with corticosteroid therapy (OR = 16.403, 95% CI = 4.433–62.111, p < 0.001). COVID-19 vaccination was associated with a significant reduction in mortality risk, with vaccinated patients exhibiting a 58% lower hazard of death compared with unvaccinated individuals (HR = 0.42; 95% CI: 0.28–0.62; p < 0.001). Conclusions: COVID-19 in HD patients is a multidimensional pathology, in which clinical severity and preventive strategies, such as vaccination, significantly influence survival. Acute anxiety requiring pharmacologic intervention was highly prevalent in hospitalized HD patients with COVID-19, but was not associated with worse survival (p = 0.903). Psychological burden should be recognized as an important component of care in this population. Full article

Background and Objectives: Autologous stem cell transplantation (ASCT) remains the standard of care for relapsed or refractory Hodgkin lymphoma (R/R HL), and an increasing proportion of patients receive programmed cell death protein 1 (PD-1) inhibitors prior to transplantation. Engraftment syndrome (ES) is a noninfectious inflammatory complication classically associated with neutrophil recovery; however, early peri-transplant inflammatory manifestations remain poorly characterized and may mimic infectious complications. We aimed to evaluate peri-transplant inflammatory events after ASCT, with particular emphasis on ES-compatible manifestations occurring before neutrophil engraftment and their association with prior PD-1 inhibitor exposure. Materials and Methods: In this single-center retrospective cohort study, 64 consecutive adult patients with HL undergoing ASCT between 2018 and 2025 were analyzed. ES was defined according to Spitzer and Maiolino criteria. Inflammatory manifestations fulfilling these criteria but occurring prior to neutrophil recovery were classified as pre-engraftment syndrome (pre-ES). Clinically significant events were defined by the requirement for systemic corticosteroid therapy. Clinical and laboratory parameters were compared using non-parametric statistical analyses. Results: No cases fulfilled the Spitzer criteria for classical ES, while three patients (4.7%) met the Maiolino criteria, none requiring corticosteroid therapy. Using the broader Maiolino definition, pre-ES was observed in 34 patients (53.1%) when the conventional engraftment time window was disregarded; however, only three patients required systemic corticosteroid therapy. Importantly, all three cases also fulfilled the Spitzer criteria outside the conventional time window, whereas the remaining Maiolino-defined pre-ES cases were self-limiting. All steroid-requiring pre-ES cases occurred exclusively in PD-1-exposed patients, and prior PD-1 therapy was significantly associated with severe pre-ES (p = 0.0007), although this finding is based on a very small number of events. These patients also demonstrated significantly higher early C-reactive protein (CRP) levels. Conclusions: While classical ES after ASCT was uncommon, clinically significant pre-ES occurred exclusively in PD-1-exposed patients. These early inflammatory events may represent a distinct phenotype and require prompt recognition and timely corticosteroid therapy after exclusion of infection. Prospective studies are warranted to validate these findings and refine risk stratification and monitoring strategies. Full article

Advances in pediatric oncology have markedly improved survival, shifting attention toward long-term treatment-related morbidity. Targeted agents and immune-based therapies are now widely used across pediatric malignancies and selected non-malignant conditions, often for prolonged periods and during critical windows of growth and development. Because many therapeutic targets regulate physiological pathways involved in growth, pubertal maturation, gonadal function, bone metabolism, and energy homeostasis, clinically relevant endocrine toxicity may emerge during treatment or become apparent only with extended follow-up. This narrative review summarizes pediatric evidence on endocrine and metabolic effects associated with major classes of targeted and immune-based therapies, including tyrosine kinase inhibitors, mTOR inhibitors, MAPK-pathway inhibitors (BRAF/MEK), TRK inhibitors, ALK inhibitors, immune checkpoint inhibitors, and immune effector therapies. Distinct patterns of endocrine vulnerability emerge across drug classes: growth impairment and bone–mineral alterations are most consistently reported with tyrosine kinase inhibitors; weight gain and metabolic changes predominate with MAPK-, TRK-, and ALK-targeted agents; immune checkpoint inhibitors are characterized by early, multi-axis immune-related endocrinopathies with a high likelihood of permanent hormone deficiency once established. In contrast, endocrine abnormalities observed after immune effector therapies largely reflect indirect effects of systemic inflammation, corticosteroid exposure, and prior hematopoietic stem cell transplantation rather than direct endocrine toxicity. Given the limited pediatric-specific data, frequent confounding by multimodal therapy, and the potential for delayed or irreversible endocrine sequelae, structured endocrine monitoring and long-term survivorship care are essential for children exposed to modern anticancer therapies. Full article

Objective: Clinical remission is a major therapeutic goal in systemic lupus erythematosus (SLE) because of its association with improved long-term outcomes. However, its relationship with patient-reported burden, quality of life, and disease perception remains incompletely understood. This study aimed to evaluate patient-reported outcomes (PROs) in patients with SLE in clinical remission, identify factors associated with impaired health-related quality of life (HRQoL), and assess physician–patient discordance in disease activity perception. Methods: A total of 106 adult patients with SLE in clinical remission according to the definition proposed by Zen et al. were enrolled at a single rheumatology center. Patients were classified into complete remission, clinical remission off corticosteroids, or clinical remission on corticosteroids. Demographic, clinical, and treatment-related data were collected, including organ damage (SLICC-SDI) and disease activity (SLEDAI-2K). Patients completed PRO measures including SF-36, Global Health (GH), pain VAS, STAI-Y1 and STAI-Y2, Zung Depression Scale, Insomnia Severity Index, and HAQ. Disease activity was assessed by both the patient (PGA) and the physician (PhGA); a PGA–PhGA difference >25 mm was considered clinically relevant discordance. Results: Among patients in clinical remission, mild anxiety was observed in 17.1% according to STAI-Y1 and in 27.9% according to STAI-Y2, mild-to-moderate depressive symptoms in 47.1%, and mild insomnia in 25.5%. Of the 106 patients, 24 (22.6%) were in complete remission, 27 (25.5%) in clinical remission off corticosteroids, and 55 (51.9%) in clinical remission on corticosteroids. Patients in clinical remission on corticosteroids showed worse patient-reported outcomes than those in complete remission or clinical remission off corticosteroids. In multivariable analyses, poorer physical HRQoL was independently associated with functional disability, pain intensity, and depressive symptoms, whereas poorer mental HRQoL was independently associated with trait and state anxiety. Clinically relevant physician–patient discordance was observed in 22.6% of the cohort and was almost exclusively driven by higher patient than physician scores. Pain intensity emerged as the most robust independent correlate of discordance. Conclusions: A substantial patient-reported burden may persist in patients with SLE despite clinical remission. Pain, psychological distress, insomnia, and functional disability contribute to impaired HRQoL, while physician–patient discordance appears to reflect a broader mismatch between inflammatory disease control and the patient’s lived experience of illness. These findings support a more comprehensive and patient-centered approach to remission assessment in SLE. Full article

Background and Objectives: The vedolizumab clinical decision support tool (VDZ-CDST) was developed to predict treatment outcomes in inflammatory bowel disease (IBD). While validated in clinical trial and consortium settings, its real-world performance remains less clear. The aim of our study was to evaluate the predictive value of pre-treatment CDST stratification for clinical and endoscopic outcomes and treatment persistence in real-world VDZ-treated IBD patients. Materials and Methods: We conducted a retrospective analysis of consecutive IBD patients initiating vedolizumab therapy, stratified by CDST risk groups. Clinical remission (CR) and corticosteroid-free remission (CSFR) at weeks 14 and 52 were assessed using PRO-2 in both Crohn’s disease (CD) and ulcerative colitis (UC). Endoscopic outcomes and treatment persistence were also evaluated. Results: 129 IBD patients, 57 with CD and 72 with UC, treated with vedolizumab were retrospectively stratified according to VDZ-CDST. In CD at week 52 the differences in CSFR between CDST groups were statistically significant (p = 0.04). A statistically significant association (p < 0.001) was also observed between CDST groups and endoscopic activity (EA) at follow-up endoscopy. In the low-probability group 69.2% showed persistent EA, whereas in the high-probability group 68.8% achieved endoscopic remission (ER). We also found significant differences (p = 0.004 and p < 0.001, respectively) in treatment persistence between CDST groups in CD. VDZ discontinuation rates were 76.9%, 28.6%, and 6.3% in the low-, intermediate-, and high-response groups, respectively. In UC, no predictive association was observed for either clinical or endoscopic outcomes nor treatment persistence; however, we observed relatively high remission rates despite CDST-based stratification. Conclusions: Although the VDZ-CDST failed to predict CR measured by PRO-2 in real-world IBD patients, it demonstrated meaningful associations with long-term CSFR, endoscopic outcomes and treatment persistence in Crohn’s disease. These findings support its role as a supportive tool in therapeutic decision-making, particularly when objective outcomes such as mucosal healing are prioritized. Prospective multicentre studies incorporating biomarkers and pharmacokinetic data are needed to refine VDZ-CDST for broader clinical application. Full article

Background/Objectives: Severe asthma in routine practice often involves long-standing disease, multimorbidity, and prior biologic failure—settings underrepresented in pivotal tezepelumab trials. This study evaluated 52-week real-world effectiveness and safety of tezepelumab in a highly comorbid, predominantly T2-high, biologic-experienced severe asthma cohort from the Canary Islands. Methods: TEZNERIFE is a multicenter, retrospective study including consecutive adolescents and adults with GINA Step 5 severe uncontrolled asthma treated with tezepelumab 210 mg every 4 weeks for 12 months. Clinical outcomes, lung function, type 2 biomarkers, upper airway symptoms, and Biologics Asthma Response Score (BARS) were assessed at baseline, 26 weeks, and 52 weeks. Results: Fifty-six patients (mean age 53.5 years, 71% female, mean asthma duration 30 years, 84% T2-high; 71% with ≥1 prior biologic) were analyzed. ACT improved from 11.5 ± 3.7 to 15.9 ± 4.7 at 26 weeks and 17.5 ± 4.7 at 52 weeks (both p < 0.0001), while annualized exacerbations declined from 2.79 ± 2.0 to 0.50 ± 0.72 and 0.51 ± 0.89 (both p < 0.0001). Maintenance oral corticosteroid dose fell from 10.2 ± 8.3 to 6.9 ± 2.4 mg/day at 52 weeks (p = 0.014). FEV1% predicted increased from 69.3 ± 19.2% to 75.3 ± 17.7% and 76.2 ± 20.6% (p = 0.004 and p = 0.001), and blood eosinophils decreased from 234 ± 231 to 146 ± 120 and 147 ± 110 cells/µL (p = 0.001 and p = 0.013). At one year, 18.9% and 67.9% were classified as good and intermediate responders by BARS; 13.2% were insufficient responders. Two patients discontinued due to non-serious adverse events, while no treatment-related serious events occurred. Conclusions: In this difficult-to-treat, multimorbid, biologic-experienced population, tezepelumab achieved sustained improvements in asthma control, exacerbations, lung function, eosinophilic inflammation, and corticosteroid exposure over 52 weeks, supporting upstream alarmin inhibition as a versatile strategy in complex severe asthma. Full article