Complexo Hospitalario Universitario A Coruña

Introduction: The clinical outcome of switching to levodopa-entacapone-carbidopa intestinal gel (LECIG) after failure of subcutaneous foslevodopa/foscarbidopa (fLD/fCD) is unknown. We analyze it in people with Parkinson's disease (PwP) treated in Spain. Methods: Retrospective analysis of PwP who had previously received fLD/fCD but dropped out for different reasons and started before this LECIG in Spain up to 30 November 2025. Non-parametric tests were applied to evaluate the changes between the pre- (Vpre) and post-treatment (Vpost) (LECIG) periods. Results: Data about 14 patients (57.1% males; 66.6 ± 8.6 years old) from 12 hospitals out of a total of 15 who were treated with LECIG were included. The mean time with fLD/fCD was 98.6 ± 92.3 days, with 92.9% and 57.1% experiencing side effects and lack of response, respectively. Specifically, significant subcutaneous nodules were reported in up to 64.3% of the patients. LECIG was a direct switch from fLD/fCD in 35.7% of the patients. LECIG was well tolerated, with only one dropout due to complications related to dementia. Adverse events were reported in 28.6% and 35.7% of the patients in the optimization and final follow-up evaluation (mean follow-up of 233.7 ± 157.4 days) phases, respectively. From Vpre to Vpost, "Off" time was reduced in 2.9 ± 1.9 h (p = 0.002) and motor symptoms burden improved significantly (p = 0.013), whereas a trend of significance was found for non-motor symptoms burden (p = 0.050) and quality of life (p = 0.126). Conclusions: LECIG could be an alternative therapeutic option in PwP who failed fLD/fCD.

ABSTRACT BACKGROUND Peak oxygen uptake (pVO 2 ) is a strong, independent predictor of adverse cardiovascular outcomes, supporting cardiopulmonary exercise testing as a primary end point assessing efficacy of novel drug therapies in obstructive hypertrophic cardiomyopathy (oHCM) clinical trials. However, characterizing changes in pVO 2 that patients perceive as beneficial or meaningful (ie, minimal important difference [MID]) has not been determined. METHODS Data from patients with symptomatic oHCM enrolled in SEQUOIA-HCM and MAPLE-HCM were pooled. A total of 282 patients were randomized 1:1 to aficamten (5–20 mg daily) or matching placebo in SEQUOIA-HCM, and 175 patients were randomized 1:1 to aficamten (5-20mg daily) or to metoprolol (50–200 mg) in MAPLE-HCM; follow-up in both trials was 24 weeks. Primary outcome was change from baseline to week 24 (Δ) in pVO 2 using Patient Global Impression of Change with anchor-based analysis to define MID. RESULTS At week 24, ΔpVO 2 (mL/kg/min) that corresponded to no change, one-category improvement, and one-category worsening were –0.05 (95% CI, –0.58 to 0.48), +0.35 (95% CI, –0.22 to 0.91), and –0.61 (95% CI, –1.36 to 0.13), respectively. Similarly, minute ventilation to carbon dioxide production ratio (VE/VCO 2 ) slope that corresponded to no change, one-category improvement, and one-category worsening were 0.16 (95% CI, –0.59 to 0.90), –1.15 (95% CI, – 1.89 to –0.42), and 0.88 (95% CI, –0.42 to 2.19), respectively. In a responder analysis using this new threshold for pVO 2 , 60% of patients receiving aficamten achieved a ΔpVO 2 ≥0.35 versus 31% of patients on placebo or metoprolol (odds ratio, 3.4 [95% CI, 2.3–4.9], P <0.001). Consistent findings were seen with VE/VCO 2 responder analysis. CONCLUSIONS Changes in pVO 2 of +0.35 and –0.61 mL/kg/min were associated with a small but perceptible clinical improvement and worsening, respectively, in patients with oHCM. Applying this newly defined threshold resulted in excellent differentiation of treatment effect in a clinical trial. These novel data provide a measure of clarity to patients and clinicians regarding the interpretation of changes in pVO 2 following therapeutic interventions, with potential impact on HCM management strategies and future clinical trials. Clinical Trial Registration SEQUOIA-HCM ( NCT05186818 ; https://clinicaltrials.gov/study/NCT05186818?term=sequoia-hcm&rank=1 ); MAPLE-HCM ( NCT05767346 ; https://clinicaltrials.gov/study/NCT05767346?term=maple-hcm&rank=1 ) Clinical Perspective What Is New? Using pooled data from over 440 patients with symptomatic obstructive hypertrophic cardiomyopathy enrolled in two phase 3 clinical trials, we define, for the first time, the minimally important difference for peak oxygen uptake (pVO 2 ) and ventilatory efficiency (VE/VCO 2 ) using patient-anchored and distribution-based methodologies. A change in pVO 2 of +0.35 mL/kg/min and a change in VE/VCO 2 of –1.15 represent the minimal thresholds associated with patient-perceived clinical improvement. Responder analyses using these thresholds demonstrated robust differentiation between aficamten and placebo/metoprolol, with an odds ratio exceeding 3 for achieving a meaningful improvement in pVO 2 . What Are the Clinical Implications? These newly defined thresholds bridge the gap between statistically significant changes in cardiopulmonary exercise testing measures and clinically meaningful benefit as perceived by patients with obstructive hypertrophic cardiomyopathy. Clinicians can use these benchmarks to contextualize individual patient responses to medical therapy, informing shared decision-making regarding treatment continuation or modification. These data provide a standardized, patient-centered framework for designing and interpreting primary end points in future hypertrophic cardiomyopathy clinical trials.

<h3>Background and Importance</h3> Antimicrobial stewardship programmes (ASP) have gained increasing relevance in recent years, particularly in critically ill patients admitted to intensive care units (ICU). These patients often receive multiple antibiotics due to their clinical complexity, which makes stewardship interventions essential for improving treatment adequacy and reducing unnecessary exposure. <h3>Aim and Objectives</h3> To evaluate the acceptance rate of antibiotic stewardship interventions in critically ill patients. <h3>Material and Methods</h3> A retrospective, observational, single-centre study was conducted over six months (January–June 2024). All ASP interventions regarding antimicrobial therapy in ICU patients were included. Interventions were classified as antibiotic discontinuation, de-escalation, pharmacokinetic/pharmacodynamic (pK/pD) optimisation, escalation, and requests for additional diagnostic tests such as blood cultures. <h3>Results</h3> A total of 197 recommendations were issued, of which 84.7% (n=167) were accepted by treating physicians. The most frequent intervention was antibiotic discontinuation (n=111), accepted in 82.9% (n=92) of cases. Agents most frequently discontinued were J01XX group antibiotics (linezolid, tedizolid, daptomycin) (n=46), with an acceptance rate of 82.6% (n=38). De-escalation accounted for 19.8% (n=39) of interventions, with 82.1% acceptance (n=32). The most frequent targets were ceftolozane/tazobactam, ceftazidime/avibactam, and ceftaroline (n=18), accepted in 66.7% (n=12), followed by carbapenems (n=10), accepted in 90% (n=9). pK/pD optimisation (n=14) achieved the highest acceptance rate among major interventions (85.7%, n=12). Escalation was proposed in 12 cases, accepted in 91.7% (n=11). Additional diagnostic tests were recommended in 13 cases, with full acceptance (100%). <h3>Conclusion and Relevance</h3> Antibiotic discontinuation was the most frequent ASP intervention, whereas de-escalation and pK/pD optimisation achieved the highest acceptance rates. Overall, the high acceptance rate (84.7%) highlights the value of multidisciplinary stewardship teams in optimising antimicrobial therapy and ensuring adequate treatment of critically ill patients. The hospital pharmacist plays a key role in this team due to their knowledge of these medications. <h3>Conflict of Interest</h3> No conflict of interest

<h3>Background and Importance</h3> The evaluation of avoided cost (AC) in investigational medicines addresses the economic dimension of clinical trials, an objectively quantifiable factor. Although sponsors are legally required to provide study drugs free of charge, this aspect remains under-reported in our setting. Quantifying AC is essential to assess the real economic impact of clinical trials, especially in diseases with high pharmaceutical expenditure such as transthyretin amyloidosis. <h3>Aim and Objectives</h3> The aim of this study was to quantify the avoided drug cost associated with the participation of patients in clinical trials on transthyretin amyloidosis, in order to assess their real economic impact on the healthcare system. <h3>Material and Methods</h3> A retrospective observational study was conducted in a tertiary hospital including clinical trials on transthyretin amyloidosis from 2019 to 2024. Trials were included if they were active during this period, investigated medicines already marketed by March 2025, and provided study drugs free of charge by the sponsor. Trials with no patients enrolled were excluded. Data were obtained from the institutional clinical trial management software and the pharmacy department database. For each trial, information was collected on protocol code, phase, scope, sponsor, investigational drug, number of enrolled patients, doses dispensed per patient, and drug cost (ex-factory price + VAT – applied discounts). The primary outcome was the total avoided cost over the period 2019–2024, while the secondary outcome was the mean avoided cost per patient. AC was calculated assuming patients would have received the same treatment, dose and regimen outside the clinical trial. <h3>Results</h3> During 2019–2024, two clinical trials on transthyretin amyloidosis were conducted; only one met the inclusion criteria. This was an international, multicentre, industry-sponsored phase III trial evaluating tafamidis in both hereditary and wild-type forms of the disease. The total avoided cost reached €9,710,268 over the study period, with a mean avoided cost per patient of €134,865, corresponding to an approximate annual saving of €1.9 million. <h3>Conclusion and Relevance</h3> The participation of hospitals and patients in clinical trials contributes significantly to reducing direct drug costs associated with transthyretin amyloidosis. Beyond this economic impact, clinical trials also reinforce the sustainability of healthcare systems, foster scientific progress and facilitate early patient access to innovative therapies. <h3>Conflict of Interest</h3> No conflict of interest

Background: The pathophysiological mechanism of eosinophilic esophagitis (EoE) is complex and is still being investigated. We believe that there is a group of patients with eosinophilic esophagitis which could be differentiated as having an allergic phenotype who exhibit a sensitization profile (aeroallergens, panallergens, foods and specific IgG4 levels) with significant differences compared to patients with conventional allergic disease without associated eosinophilic esophagitis and healthy controls. Method: We measured the prevalence of sensitization to aeroallergens, foods and panallergens by means of molecular diagnostic techniques (ImmunoCAPTM ISAC) and determined the levels of specific IgG4 against foods and eosinophilic-derived neurotoxin (EDN) (ImmunoCAP technology) in patients with EoE of an allergic phenotype to study whether there are statistically significant differences with respect to the control groups (patients with different allergic pathologies without EoE and healthy patients without documented allergies). The total number of patients under study was 118, distributed among the different study groups. The case group (Allergic phenotype EoE patients) had 48 subjects. The food and respiratory allergy control groups had 30 subjects each. Finally, we included 10 in the healthy control group. Results: We were able to identify statistically significant differences when comparing levels of food-specific IgG4. Milk, egg, wheat, nuts, soy, cod, and Pru p3/LTP stood out. We did not observe significant differences in relation to sensitization to aeroallergens, foods, or panallergens. We also did not observe differences in EDN levels. Conclusions: We present a study in which statistically significant differences in IgG4 levels were observed in response to different types of food, comparing patients with eosinophilic esophagitis of allergic phenotype (case group) against subjects with allergic pathology without EoE and healthy subjects (control groups). Determining whether the detected foods are clinically relevant or not in these patients would be fundamental to establishing their usefulness as a treatment alternative in our patients.

Aortitis associated with giant cell arteritis (GCA) is a severe manifestation, potentially leading to aneurysms and aortic dissection. Tocilizumab (TCZ) has demonstrated efficacy in the treatment of GCA, both intravenously or subcutaneously administered. However, pivotal studies did not specifically evaluate aortic involvement, and no comparison of intravenous (IV) versus subcutaneous (SC) TCZ has been performed in patients with GCA-related aortitis. The objective of this study was to compare the effectiveness of TCZ according to the administration route in patients with GCA-associated aortitis under clinical practice conditions. This was a multicenter observational study including 196 patients diagnosed with GCA-associated aortitis by imaging and treated with TCZ. Patients were grouped by administration route: IV or SC. GCA was diagnosed following the 1990 American College of Rheumatology criteria, temporal artery biopsy, and/or vascular imaging. Aortitis was identified using 18F-fluorodeoxyglucose positron emission tomography/computed tomography scan. Main outcomes included EULAR remission, clinical and imaging remission, absence of systemic inflammation, and glucocorticoid-sparing effect. Of 196 patients (148 women; mean age 69.8 ± SD 9.4 years), 110 received IV TCZ and 86 SC TCZ. Baseline clinical characteristics and markers of inflammation were comparable between groups. The glucocorticoid-sparing effect was similar. At 24-month follow-up, EULAR-defined remission was significantly more frequent in the SC group (83.3% vs 80.6%; P < 0.05). However, rates of imaging remission and absence of systemic inflammation were comparable between treatment arms. In this real-world cohort of GCA-associated aortitis, SC TCZ showed slightly greater effectiveness than IV TCZ in achieving EULAR-defined remission, whereas no significant differences were observed between both routes regarding imaging remission.