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Advanced Doppler Ultrasound Insights: A Multicenter Prospective Study on Healthy Skin
Full text linkCutaneous doppler ultrasound; Healthy skin; Visible vesselsEcografía doppler cutánea; Piel sana; Vasos visiblesEcografia doppler cutània; Pell sana; Vasos visiblesBackground: There have been multiple studies on the use of Doppler ultrasound to define skin inflammation, but the visible vessels of healthy skin have yet to be described. Objective: This study aimed to evaluate the visible vessels of healthy skin using Doppler ultrasound. Methods: Prospective multicenter study using Doppler ultrasound to analyze healthy skin. The color percentage, flow velocity, and maximum vessel diameter were calculated. Results: 943 images from 152 patients were recorded. The most frequently used mode was color Doppler (40.6%), followed by power Doppler (30.4%). Visible vessels were detected in 18.23%; in positive Doppler images, color occupied less than 5%. The malar region exhibited the highest visible vessels. The 22 MHz probe detected smaller vessels with slower flows than the 18 MHz probe. Spectral Doppler showed peak systolic values of less than 10 cm/s and a vessel diameter of less than 1 mm. In most of the participating centers, the operators had less than 10 years of experience in performing skin ultrasound examinations. Sensitivity of the Doppler may vary according to the device. Conclusions: With the used ultrasound equipment, it was uncommon to visualize vessels in healthy skin. When seen, they covered less than 5% of the image with low flow and small size
Efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal cancer
Full text linkColorectal cancer; Gastrointestinal cancer; TRK fusionCàncer colorectal; Càncer gastrointestinal; Fusió TRKCáncer colorrectal; Cáncer gastrointestinal; Fusión TRKBackground
Larotrectinib is the first-in-class, highly selective TRK inhibitor with demonstrated efficacy in various TRK fusion solid tumours. We report the efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal (GI) cancer.
Methods
Patients with TRK fusion GI cancer from NAVIGATE (NCT02576431) were included. Response was independent review committee (IRC)-assessed per RECIST v1.1.
Results
As of July 2023, 44 patients were enrolled. Tumour types included colorectal (CRC; n = 26), pancreatic (n = 7), cholangiocarcinoma (n = 4), gastric (n = 3), and one each of appendiceal, duodenal, oesophageal and hepatic cancers. Of the 26 patients with CRC, 16 (62 %) had known microsatellite instability-high (MSI-H) status. For the 43 IRC-eligible patients, overall response rate was 28 % (95 % confidence interval [CI] 15–44) for all patients and 44 % (95 % CI 24–65) for those with CRC. In patients overall and in those with CRC, median duration of response was 27 months (95 % CI 6–not estimable [NE]) and 27 months (95 % CI 6–NE), median progression-free survival was 6 months (95 % CI 5–9) and 7 months (95 % CI 6–NE), and median overall survival was 13 months (95 % CI 7–29) and 29 months (95 % CI 7–NE), respectively. Grade 3/4 treatment-related adverse events (TRAEs) occurred in seven (16 %) patients. There were no deaths due to TRAEs.
Conclusion
Larotrectinib demonstrated long durability, extended survival and manageable safety in patients with TRK fusion GI cancer, including those with MSI-H CRC. This supports the wider adoption of next-generation sequencing testing for NTRK gene fusions in patients with GI cancer.These studies were funded by Bayer Healthcare and Loxo Oncology, Inc., a wholly owned subsidiary of Eli Lilly and Company. Dr Drilon was supported in part by the National Cancer Institute of the National Institutes of Health P30 CA008748, 1R01CA226864–01A1 and Nonna’s Garden
Mobilizing community health assets through intersectoral collaboration for social connection: Associations with social support and well-being in a nationwide population-based study in Catalonia
Full text linkCol·laboració intersectorial; Àmbit social; AssociacionismeColaboración intersectorial; Ámbito social; AsociacionismoIntersectoral collaboration; Social connection; AssociationismLimited social connection among older adults poses a global public health challenge, reducing sources of support and affecting health and well-being. National public health strategies that leverage local intersectoral collaboration between key sectors such as primary and social care, community organizations, and society, have been advocated, yet their impact remains underexplored.
This study examines the regional variability in the uptake of a public health strategy in Catalonia that mobilizes community health assets, such as social clubs and leisure activities, through intersectoral collaboration and its associations with social support and mental well-being in older adults.
We conducted a population-based cross-sectional study using the Catalan Health Survey (2017-2021) with 6011 adults aged ≥ 60 years across 31 Health Sectors. Survey data were linked with area-level uptake metrics, generated using data analytic techniques. Individuals were categorized into three uptake groups based on the number and territorial distribution of asset-based initiatives within their area of residence. Multilevel regressions tested associations with social support (OSSS-3) and mental well-being (SWEMWBS), controlling for individual, contextual, and temporal factors.
Participants' average age was 74.1 years ± 10.0 with 53.3% women. From 2017 to 2021, 2312 asset-based initiatives were registered across Health Sectors, ranging from 0 to 342 per sector. Residing in sectors with the highest uptake of initiatives (>15 initiatives per 10,000 population) was associated with higher social support (β = .34, p < .01) and mental well-being scores (β = 1.11, p < .01).
Residing in areas with greater health assets mobilized through intersectoral collaboration was associated with higher social support and well-being among older adults. This study represents one of the first national evaluations of an intersectoral strategy aimed at mitigating the mental health impacts of limited social networks. Future public health strategies should prioritize equitable access for inclusive benefits
Valor clínico y económico de la bulevirtida en el tratamiento de la hepatitis D crónica
Full text linkTratamiento antiviral; Hepatitis delta crónica; Virus de la hepatitis DAntiviral therapy; Chronic hepatitis delta; Hepatitis D virusTeràpia antiviral; Hepatitis delta crònica; Virus de l'hepatitis DBackground/Aims
Bulevirtide (Hepcludex®) is the first drug approved for the treatment of chronic hepatitis D (CHD), unlike the current off-label treatment (PEG-IFN-α), limited in clinical practice and associated with post-treatment relapses. In a hypothetical cohort of CHD patients in Spain, the study aim was to compare the efficiency of bulevirtide with PEG-IFN-α in terms of clinical events avoided and associated cost savings.
Methods
A validated economic model reflecting the natural history of the disease was used to project lifetime liver complications and costs for two hypothetical cohorts treated with bulevirtide or PEG-IFN-α. The model considered progression to complications such as decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), liver transplantation (LT), and death. The efficacy rates used at 24 and 48 weeks were defined as the combined response rate for bulevirtide and undetectable HDV RNA to PEG-IFN-α. The numbers of clinic events and associated costs were evaluated from the perspective of the National Healthcare System.
Results
In a hypothetical cohort of 3882 patients, bulevirtide reduced the numbers of complications events in comparison to PEG-IFN-α (152 DCC, 113 HCC, 11 LT, and 321 deaths over a lifetime). This was associated with a reduction of event-related costs of €11,837,044 (DCC €1,138,059; HCC €1,503,583; LT €7,834,291; and death €1,361,111).
Conclusion
In patients with CHD, bulevirtide could prevent a significant number of clinical events compared to PEG-IFN-α and contribute to cost savings through these reduction in liver complications. Further testing for hepatitis D virus is needed so that more patients can benefit from bulevirtide.Antecedentes/Objetivos
La bulevirtida (Hepcludex®) es el primer tratamiento aprobado para la hepatitis D crónica (HDC), a diferencia del tratamiento con PEG-IFN-α (fuera de indicación) limitado en la práctica clínica por estar asociado a recidivas tras el tratamiento. El objetivo fue comparar la eficacia de bulevirtida vs. PEG-IFN-α en términos de eventos clínicos evitados y ahorro de costes asociados en una cohorte hipotética de pacientes con HDC en España.
Métodos
Se utilizó un modelo económico validado que refleja la historia natural de la enfermedad mediante la simulación de complicaciones hepáticas (cirrosis descompensada [CD], carcinoma hepatocelular [CHC], trasplante hepático [TH] y muerte) durante la vida del paciente. Se emplearon tasas de eficacia a las 24 y 48 semanas, considerando la tasa de respuesta combinada para bulevirtida y el ARN-VHD indetectable para PEG-IFN-α. Los eventos clínicos y sus costes asociados se evaluaron desde la perspectiva del Sistema Nacional de Salud.
Resultados
En una cohorte hipotética de 3.882 pacientes, bulevirtida redujo el número de complicaciones en comparación con PEG-IFN-α (152 CD, 113 CHC, 11 TH y 321 muertes, a lo largo de la vida). Esto supuso una reducción de 11.837.044 € (1.138.059 € CD, 1.503.583 € CHC, 7.834.291 € TH y 1.361.111 € muertes hepáticas).
Conclusiones
En pacientes con CHD, bulevirtida (Hepcludex®) podría prevenir un número significativo de complicaciones clínicas en comparación con PEG-IFN-α y contribuir al ahorro de costes a través de esta reducción de las complicaciones hepáticas. Es necesario realizar más pruebas de detección del virus de la hepatitis D para que más pacientes puedan beneficiarse de bulevirtida.This work has been funded by Gilead Sciences Spain
An update on diagnosis and treatments of childhood interstitial lung diseases
Full text linkDiagnosis; Treatments; Childhood interstitial lung diseasesDiagnòstic; Tractament; Malalties pulmonars intersticials infantilsDiagnóstico; Tratamiento; Enfermedades pulmonares intersticiales infantilesChildhood interstitial lung diseases (chILDs) are rare and heterogeneous disorders associated with significant morbidity and mortality. The clinical presentation of chILD typically includes chronic or recurrent respiratory signs and symptoms with diffuse radiographic abnormalities on chest imaging. Diagnosis requires a structured, multi-step approach. Treatment options are limited, with disease-specific therapies available only in selected cases and management relying primarily on supportive care. Awareness of chILDs has been steadily increasing. New diagnoses, advanced diagnostic tests, and novel treatments are emerging each year, highlighting the importance of collaborative, multidisciplinary teams in providing comprehensive care for children and families affected by these complex conditions. On behalf of the European Respiratory Society Clinical Research Collaboration for chILD (ERS CRC chILD-EU), this review provides an updated overview of the diagnostic approach and management strategies for chILDs
TROPION-Breast05: a randomized phase III study of Dato-DXd with or without durvalumab versus chemotherapy plus pembrolizumab in patients with PD-L1-high locally recurrent inoperable or metastatic triple-negative breast cancer
Full text linkDurvalumab; Immunotherapy; Triple-negative breast cancerDurvalumab; Inmunoterapia; Cáncer de mama triple negativoDurvalumab; Immunoteràpia; Càncer de mama triple negatiuBackground:
Standard of care (SoC) for patients with advanced triple-negative breast cancer (TNBC) whose tumors express PD-L1 (combined positive score ⩾ 10) is chemotherapy plus anti-PD-(L)1 inhibitors; however, prognosis and survival for most patients is poor. Datopotamab deruxtecan (Dato-DXd), a novel antibody-drug conjugate comprising a humanized anti-TROP2 IgG1 monoclonal antibody conjugated to a potent topoisomerase I inhibitor payload via a plasma-stable, cleavable, tetrapeptide-based linker, has shown preliminary activity as mono or combination therapy in advanced/metastatic TNBC.
Objectives:
TROPION-Breast05 is an ongoing randomized, open-label, multicenter phase III study. The primary objective is to demonstrate the superiority of Dato-DXd in combination with durvalumab (an anti-PD-L1 antibody) versus SoC treatment in patients with PD-L1-high locally recurrent inoperable or metastatic TNBC.
Methods and design:
Patients (⩾18 years) will be randomized 1:1 to receive Dato-DXd (6 mg/kg intravenously (IV) every 3 weeks (Q3W)) plus durvalumab (1120 mg IV Q3W) or investigator’s choice of chemotherapy (ICC; paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin) plus pembrolizumab (200 mg IV Q3W). In selected countries, patients will also be randomized (1:1:1) to a third arm of Dato-DXd monotherapy. The primary study endpoint is progression-free survival (PFS) per blinded independent central review (Dato-DXd plus durvalumab arm vs ICC plus pembrolizumab arm). Overall survival is a key secondary endpoint; other secondary endpoints include PFS (investigator-assessed), objective response rate, duration of response, clinical benefit rate at Week 24 (all assessed in the Dato-DXd plus durvalumab arm vs ICC plus pembrolizumab arm), patient-reported outcomes, and safety.
Ethics:
The study is approved by independent ethics committees or institutional review boards at each study site. All patients will provide written informed consent.
Discussion:
TROPION-Breast05 will assess the potential role of Dato-DXd with or without durvalumab in patients with PD-L1-high advanced or metastatic TNBC. The findings of this trial could lead to a new treatment option for these patients.
Trial registration:
ClinicalTrials.gov identifier: NCT06103864 (Date of registration: 27 October 2023).The TROPION-Breast05 study (NCT06103864) is sponsored by AstraZeneca. In July 2020, Daiichi Sankyo entered into a global development and commercialization collaboration with AstraZeneca for datopotamab deruxtecan (Dato-DXd)
Oral antibiotic prophylaxis induces changes in the microbiology of surgical site infection after colorectal surgery. A matched comparative study
Full text linkColorectal surgery; Surgical site infection; Cohort studiesCirugía colorrectal; Infección del sitio quirúrgico; Estudios de cohorteCirurgia colorrectal; Infecció del lloc quirúrgic; Estudis de cohortsAim: Oral antibiotic prophylaxis (OAP) lowers rates of surgical site infection (SSI) and may aid anastomotic healing in colorectal surgery. The aim of this study was to analyse the understudied impact of OAP on SSI microbiology after colorectal surgery.
Method: A post hoc analysis was performed on a previous prospective, multicentre study of elective colorectal surgery. For 1000 patients with SSI, this study compared the microbiology of SSIs in procedures without OAP (SSI/OAP-) and with OAP (SSI/OAP+).
Results: There were 340 patients in the SSI/OAP- group and 660 in the SSI/OAP+ group. The use of OAP increased the presence of Gram-positive cocci (GPC) (OR 1.542, 95% CI 1.153-2.062) and fungi (OR 2.037, 95% CI 1.206-3.440), but reduced rates of Gram-negative bacteria (GNB) (OR 1.461, 95% CI 1.022-2.088) and anaerobe isolation (OR 0.331, 95% CI 0.158-0.696). Specifically, it led to increases in the isolation of Enterococcus faecium (OR 1.450, 95% CI 0.812-2.591), methicillin-resistant Staphylococcus aureus (OR 2.000, 95% CI 1.043-3.834) and Candida spp. (OR 2.037, 95% CI 1.206-3.440). In colon surgery with OAP, GPC infections were more likely (OR 1.461, 95% CI 1.022-2.088). In rectal surgery, organ/space SSIs had a higher risk of harbouring GPC (OR 1.860, 95% CI 1.153-2.999) and a lower risk of GNB (OR 0.321, 95% CI 0.200-0.515).
Conclusion: OAP reduced the presence of anaerobes and GNB in SSIs, but increased the isolation of GPCs and fungi, with E. faecium and Candida being of particular concern. This information should guide empirical antibiotic therapy for postoperative colorectal SSIs in patients who have received preoperative OAP.The Surveillance of Healthcare Related Infections in Catalonia (VINCat) programme is supported by public funding from the Catalan Health Service, Department of Health, Generalitat de Catalunya
Nedosiran in pediatric patients with PH1 and relatively preserved kidney function, a phase 2 study (PHYOX8)
Full text linkChronic kidney disease; Gene expression; HyperoxaluriaMalaltia renal crònica; Expressió gènica; HiperoxalúriaEnfermedad renal crónica; Expresión génica; HiperoxaluriaBackground: Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder with dysregulated glyoxylate metabolism in the liver. Oxalate over-production leads to renal stones, progressive kidney damage and renal failure, with potentially life-threatening systemic oxalosis. Nedosiran is a synthetic RNA interference therapy, designed to reduce hepatic lactate dehydrogenase (LDH) to decrease oxalate burden in PH.
Methods: Currently, in the PHYOX8 study (NCT05001269), pediatric participants (2-11 years) with PH1 (N = 15) and estimated glomerular filtration rate (eGFR) ≥ 30mL/min/1.73m2 received nedosiran once monthly for 6 months.
Results: Urinary oxalate:creatinine (Uox:Ucr) levels reduced by 64% on average. Mean Uox:Ucr reduction was 52% at day 60 and ˃60% at day 180. At one or more study visits, 93.3% (N = 14) of participants reached Uox:Ucr < 1.5 × upper limit of normal (ULN), and 53.3% (N = 8) reached ≤ 1.0 × ULN. Median percent change in plasma oxalate (12.0 µmol/L at baseline) to day 180 was -39.23% (n = 10). Average number of kidney stones per participant remained stable, whilst a 10.1% average decrease in summed surface area was observed. Median percent change from baseline in eGFR was 2.5%, indicating preservation of renal function.
Conclusions: Nedosiran was well tolerated, with only 3 participants experiencing at least one serious adverse event, none considered treatment-related. The incidence of injection site reactions was 6.7% (1/15 participants). In conclusion, nedosiran treatment led to a significant and sustained reduction of Uox levels in children with PH1. These findings support nedosiran treatment in pediatric patients to reduce Uox and shows promise for limiting PH1-related complications.The study was supported by Dicerna Pharmaceuticals, Inc., a Novo Nordisk Company (Lexington, MA, USA)
AMIC achieves sustained clinical improvement in isolated patellar cartilage defects over 5 years, correlating with MRI
Full text linkCartilage; Chondral lesion; Magnetic resonance imagingCartílag; Lesió condral; Imatge per ressonància magnèticaCartílago; Lesión condral; Imagen por resonancia magnéticaPurpose
To evaluate 5-year postoperative clinical outcomes of autologous matrix-induced chondrogenesis (AMIC) for isolated ICRS grade 3–4 patellar cartilage defects and correlate outcomes with magnetic resonance imaging (MRI). The hypothesis was that AMIC would improve clinical symptoms and induce neocartilage formation, visible on MRI, making it a safe and effective option for repairing focal patellar cartilage defects.
Methods
The cohort comprised 13 focal patellar lesions in 12 patients. Pain visual analogue scale (VAS), Knee Injury and Osteoarthritis Outcome Score (KOOS), Kujala score, EuroQol-5D Health Survey questionnaire and MRI data were assessed preoperatively and at 2 and 5 years postoperatively. All MRI scans were evaluated using the Magnetic Resonance Observation of Cartilage Repair Tissue System. Descriptive statistics were calculated on all data. Inferential analysis comparing outcome scores before and after surgery employed the nonparametric Wilcoxon signed-rank test, with the nonparametric Friedman test used to detect differences across multiple test attempts. p < 0.05 was considered statistically significant.
Results
Twelve patients (23–52 years old) with patellofemoral chondral full-thickness defects (2–4 cm2) were treated. At a 5-year follow-up, eleven knees showed MRI improvement. Two were asymptomatic and nine showed clear clinical improvement. Only one knee showed no clinical improvement. MRI revealed a defect filling with newly formed cartilage characterized by a less compact and heterogeneous signal. Cartilage degradation or joint damage was observed in two knees, and bone formation within the plate was identified in four. AMIC significantly improved patients' VAS pain, KOOS, EuroQol-5D and Kujala scores compared to preoperative baseline for up to 5 years postoperatively.
Conclusions
Satisfactory clinical outcomes and new cartilage formation, as observed by MRI, are achieved with AMIC at mid-term follow-up for ICRS grade 3–4 in small-to-medium-sized patellar defects in patients under 52 years of age, with improvements maintained for up to 5 years.
Level of Evidence
Level III
Identifying germline pathogenic variants in breast cancer using tumor sequencing
Full text linkBreast cancer; Hereditary cancer; Tumor sequencingCáncer de mama; Cáncer hereditario; Secuenciación del tumorCàncer de mama; Càncer hereditari; Seqüenciació del tumorPurpose
To investigate the performance of an in-house tumor sequencing panel to identify patients with breast cancer and a germline pathogenic variant (gPV).
Patients and methods
Retrospective and blinded tumor sequencing analysis in 90 patients with breast cancer and prior germline genetic testing (45 non-carriers and 45 carriers of a gPV) using an in-house panel (VHIO-300). Sensitivity (S), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) of tumor sequencing were calculated. A Cohen's kappa coefficient ≥0.80 was predefined as minimum to be reliably acceptable for clinical implementation.
Results
The cohort included 84 women and 6 men with a median age of 48 years (29–84). Tumors of germline carriers were mainly stage II (47 % vs 31 %, P = 0.047), luminal B-like (56 % vs 31 %, p = 0.037) or triple negative (22 % vs 16 %, = 0.037). The in-house tumor panel identified 91 % (40/44) of the gPV. The analysis did not detect any of the 2 patients with germline large rearrangement alterations nor 2 of the 7 patients with intronic variants included. The tumor sequencing panel yielded 7 % of false positive results (ie, genetic alterations suggestive of germline origin). Hence, S was 91 %, Sp 93 % and Cohen's kappa coefficient between tumor and germline testing was 0.84 (95 % CI 0.73–0.95).
Conclusion
Tumor tissue sequencing with our in-house panel demonstrated an acceptable performance to identify patients with breast cancer carriers of a gPV.This work was supported by an ESMO Translational Research Fellowship and a postdoctoral grant from Swedish Society for Medical Research (Svenska Sällskapet för Medicinsk Forskning) (A.P.); Tumor sequencing was funded by VHIO; 2023SGR01112/Department of Research and Universities of the Generalitat de Catalunya and AGAUR