SAS - Hospital Universitario Virgen de la Victoria
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Publication Vol. 30, nº 26. Oportunidades perdidas y diagnostico tardío de VIH en el distrito de salud Málaga-Valle del Guadalhorce.(Consejería de Salud y Consumo, 2025-07-11) Servicio de Vigilancia y Salud LaboralEnfermedades de Declaración Obligatoria por provincias. Semana 27/2025 y acumulado desde la semana 01/2025. Datos provisionales. Incluye además el artículo titulado “Oportunidades perdidas y diagnostico tardío de VIH en el distrito de salud Málaga-Valle del Guadalhorce”, de “Mishel Renata Heredia Ruiz, María Ángeles Fernández Gómez”.Publication Efficacy and safety of cosibelimab, an anti-PD-L1 antibody, in metastatic cutaneous squamous cell carcinoma(BMJ Group, 2023-10-17) Clingan, Philip; Ladwa, Rahul; Brungs, Daniel; Harris, Dean Laurence; McGrath, Margaret; Arnold, Susan; Coward, Jermaine; Fourie, Samuel; Kurochkin, Andriy; Malan, Daniel R.; Mant, Andrew; Sharma, Vinay; Shue, Hong; Tazbirkova, Andrea; Berciano-Guerrero, Miguel-Angel; Charoentum, Chaiyut; Dalle, Stephane; Dechaphunkul, Arunee; Dudnichenko, Oleksandr; Koralewski, Piotr; Lugowska, Iwona; Montaudie, Henri; Munoz-Couselo, Eva; Sriuranpong, Virote; Oliviero, James; Desai, Jayesh; Checkpoint TherapeuticsProgrammed cell death receptor-1 (PD-1)-blocking antibodies are approved to treat metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) cases ineligible for curative surgery or radiation. Notwithstanding, some patients experience inadequate responses or severe immune-related adverse events (AEs), indicating the need for improved therapies. Cosibelimab is a high-affinity programmed cell death-ligand 1 (PD-L1)-blocking antibody that activates innate and adaptive immunity by blocking PD-L1 interaction with PD-1 and B7-1 receptors. It is an unmodified immunoglobulin G1 subtype with a functional Fc domain capable of inducing antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Here, we present results of the pivotal study of patients with metastatic CSCC from an open-label, multicenter, multiregional, multicohort, phase 1 trial of cosibelimab.MethodsIn this trial, participants with metastatic CSCC received cosibelimab 800 mg intravenously every 2 weeks. Primary endpoint was objective response rate (ORR) by independent central review using Response Evaluation Criteria in Solid Tumors, V.1.1. Secondary endpoints included duration of response (DOR) and safety.ResultsObjective response was observed in 37 of 78 participants (47.4% (95% CI: 36.0% to 59.1%)), with median follow-up of 15.4 months (range: 0.4 to 40.5) as of data cut-off. Median DOR was not reached (range: 1.4+ to 34.1+ months), with response ongoing in 73.0% of participants. Common treatment-emergent AEs (>= 15%) were fatigue (26.9%), rash (16.7%), and anemia (15.4%). Eighteen participants (23.1%) experienced immune-related AEs (grade 3: n=2 (2.6%); no grade 4/5). No treatment-related deaths were reported.ConclusionsCosibelimab demonstrated clinically meaningful ORR and DOR and was associated with a manageable safety profile.Publication Access to systemic treatment of non-melanoma skin cancer in Spain: a survey analysis.(Springer, 2024-07-01) Cerezuela-Fuentes, Pablo; Gonzalez-Cao, Maria; Puertolas, Teresa; Manzano, Jose Luis; Maldonado, Cayetana; Yelamos, Oriol; Berciano-Guerrero, Miguel A; Martin-Liberal, Juan; Muñoz-Couselo, Eva; Espinosa, Enrique; Drozdowskyj, Ana; Berrocal, Alfonso; Soria, Ainara; Marquez-Rodas, Ivan; Martin-Algarra, Salvador; Quindos, Maria; Puig, Susana; Spanish Melanoma Group (GEM)Background Novel and highly efective drugs for non-melanoma skin cancer (NMSC) improve patient outcomes, but their high cost strains healthcare systems. Spain’s decentralized public health system, managed by 17 autonomous communities (AaCc), raises concerns about equitable access. Methods A cross-sectional survey (July–September 2023) was sent to Spanish Multidisciplinary Melanoma Group (GEM Group) members to assess access to new drugs. Findings Fifty physicians from 15 Spanish AaCc responded to the survey. Access for drug with approved public reimbursement, Hedgehog inhibitors in basal-cell carcinoma and anti PD-L1 antibody in Merkel carcinoma, was observed in 84% and 86% of centers, respectively. For other EMA-approved treatments, but without reimbursement in Spain access decreased to 78% of centers. Heterogeneity in access was mainly observed intra regions. Conclusion Unequal fnancial support for drugs for NMSC with creates a patchwork of access across Spanish hospitals, with variations even within the same AaCc.Publication A Phase II Trial of the CD40 Agonistic Antibody Sotigalimab (APX005M) in Combination with Nivolumab in Subjects with Metastatic Melanoma with Confirmed Disease Progression on Anti-PD-1 Therapy.(American Association for Cancer Research, 2023-08-03) Weiss, Sarah A; Sznol, Mario; Shaheen, Montaser; Berciano-Guerrero, Miguel-Angel; Muñoz-Couselo, Eva; Rodriguez-Abreu, Delvys; Boni, Valentina; Schuchter, Lynn M; Gonzalez-Cao, Maria; Arance, Ana; Wei, Wei; Ganti, Apar Kishor; Hauke, Ralph J; Berrocal, Alfonso; Iannotti, Nicholas O; Hsu, Frank J; Kluger, Harriet M; Apexigen; Yale Calabresi Immuno-oncology Training Program; Yale SPORE in Skin CancerPurpose: Disease progression during or after anti-PD-1-based treatment is common in advanced melanoma. Sotigalimab is a CD40 agonist antibody with a unique epitope specificity and Fc receptor binding profile optimized for activation of CD40-expressing antigen-presenting cells. Preclinical data indicated that CD40 agonists combined with anti-PD1 could overcome resistance to anti-PD-1. Patients and Methods: Weconductedamulticenter, open-label, phase II trial to evaluate the combination of sotigalimab 0.3 mg/kg and nivolumab 360 mg every 3 weeks in patients with advanced melanoma following confirmed disease progression on a PD-1 inhibitor. The primary objective was to determine the objective response rate (ORR). Results: Thirty-eight subjects were enrolled and evaluable for safety. Thirty-three were evaluable for activity. Five confirmed partial responses (PR) were observed for an ORR of 15%. Two PRs are ongoing at 45.9þ and 26þ months, whereas the other three responders relapsed at 41.1, 18.7, and 18.4 months. The median durationofresponsewasatleast26months.Twoadditionalpatients had stable disease for >6 months. Thirty-four patients (89%) experienced at least one adverse event (AE), and 13% experienced a grade 3 AE related to sotigalimab. The most common AEs were pyrexia,chills, nausea,fatigue, pruritus,elevatedliverfunction, rash, vomiting, headache, arthralgia, asthenia, myalgia, and diarrhea. There were no treatment-related SAEs, deaths, or discontinuation of sotigalimab due to AEs. Conclusions: Sotigalimab plus nivolumab had a favorable safety profile consistent with the toxicity profiles of each agent. The combination resulted in durable and prolonged responses in a subset of patients with anti-PD-1-resistant melanoma, warranting further evaluation in this setting.Publication T-cell changes induced by desensitisation to BRAF inhibitors in two patients with DRESS.(Wiley-Blackwell Publishing, 2021-06-30) Salas, Maria; Berciano-Guerrero, Miguel-Angel; Palomares, Francisca; Rueda, Antonio; Fernandez, Tahia D; Mayorga, Cristobalina; Torres, Maria Jose; Andalusian Regional Ministry Health; Institute of Health “Carlos III” of the Ministry of Economy and CompetitivenessTo the Editor,Melanoma is an aggressive skin cancer, with low survival rates in pa-tients with advanced disease. Melanoma patients present mutationsin genes encoding kinases that participate in the mitogen-activatedprotein kinases (MAPK) cascade, such as RAF, encoded in BRAFgene and MEK.1 The commonest melanoma mutation is the V600E,which produces an abnormal protein that activates the MAPK cas-cade inducing cellular alterations. Besides surgical excision, there are different options according to clinical stage, like the use of drugcombinations as BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi),which inhibit the MAPK cascade activation. 2 This combination in-creases treatment effectiveness, decreases adverse effects andprevents drug resistance. 3 These drugs can induce severe cutane-ous allergic reactions (SCAR). 4 Generally, desensitisation in SCAR iscontraindicated. Moreover, in melanoma patients, desensitisationseems to be the only procedure that allows them to continue withtreatment. We have studied two melanoma patients (P1 and P2)who developed drug rash with eosinophilia and systemic symptoms(DRESS) after BRAFi administration and who tolerated this drugafter desensitisation. We have assessed T-cell involvement in skinbiopsies and peripheral blood samples at acute phase (T0), and im-munological response after desensitisation (T1). Additionally, prolif-erative response was assessed at two times.Publication Immune checkpoint inhibition in metastatic or non-resectable melanoma after failure of adjuvant anti-PD-1 treatment. A EUMelaReg real-world evidence study.(Elsevier, 2025-03-07) Weichenthal, Michael; Ellebaek, Eva; Mangana, Joanna; Asher, Nethanel; Gavrilova, Iva; Kandolf, Lidija; Ugurel, Selma; Hausschild, Axel; Meier, Friedegund; Leiter, Ulrike; Livingstone, Elisabeth; Gebhardt, Christoffer; Gutzmer, Ralf; Ruhlmann, Christina H; Mahncke-Guldbrandt, Louise; Haslund, Charlotte A; Kopec, Sylwia; Teterycz, Paweł; Bender, Marc; Poudroux, Wilfried; Muñoz-Couselo, Eva; Berciano-Guerrero, Miguel-Angel; Shalamanova, Gergana; DePalo, Danielle K; Brozic, Jasmina Maric; Chiarion-Sileni, Vanna; Arance, Anna; Ziogas, Dimitrios; Robert, Caroline; van-de-Velde, Anthonie Obik; Gassama, Awa Aminata; Shapira, Ronnie; BenBetzalel, Guy; Grynberg, Shirly; Ramelyte, Egle; Bertoldo, Fabio; DelPrete, Valerio; Gaudy-Marqueste, Caroline; Mohr, Peter; Dummer, Reinhard; Ascierto, Paolo A; Gogas, Helen; Espinosa, Enrique; Lebbe, Celeste; Rutkowski, Piotr; Haanen, John; Schadendorf, Dirk; Svane, Inge Marie; EUMelaReg Consortium MembersBackground: Adjuvant immune checkpoint inhibition (ICI) with anti-PD-1 antibodies in high-risk resected melanoma has been shown to improve recurrence-free survival. It is unclear whether prior adjuvant anti-PD-1 therapy is associated with altered response to subsequent ICI treatment in the metastatic setting. Methods: Using data from the European Melanoma Registry (EUMelaReg), we analyzed the efficiency of first-line (1L) ICI in non-resectable or metastatic melanoma after failure from prior adjuvant anti-PD-1 treatment. Both single-agent anti-PD-1 and combined anti-PD-1/CTLA-4 (Ipi/Nivo) 1L regimes were included in the analysis. We identified 389 patients receiving 1L ICI with prior adjuvant anti-PD-1 treatment. The control population was selected from a pool of 3390 PD-1-naive cases by 1:1 matching for the type of 1L ICI and various prognostic factors. As outcome measure, overall remission rates (ORR) were calculated and progression-free survival (PFS) was evaluated by Kaplan-Meier and Cox regression analysis. Results: Out of 389 patients, 303 (77.9 %) received Ipi/Nivo and 86 (22.1 %) anti-PD-1 in 1L. ORR was significantly lower in pre-treated patients (31.4 %) as compared to anti-PD-1 naive patients (48.8 %; p < 0.0001). Kaplan-Meier analysis showed significantly shorter median PFS for pre-treated patients. This applied to both anti-PD-1 and Ipi/Nivo treatment. Patients with early recurrence from adjuvant treatment (during or up to 12 weeks after end of treatment) showed lower ORR (28.5 %) and shorter PFS (3.1 months) than those who recurred later (37.7 % and 6.1 months, respectively). Conclusions: Patients with metastatic melanoma, previously exposed to anti-PD-1 ICI in the adjuvant setting showed significantly lower ORR and shorter PFS to 1L ICI with either Ipi/Nivo or single-agent anti-PD-1 retreatment.Publication Vol. 30, nº 14. Influencia de los determinantes sociales sobre la calidad de vida en pacientes con multimorbilidad y polifarmacia.(Consejería de Salud y Consumo, 2025-04-04) Servicio de Vigilancia y Salud LaboralEnfermedades de Declaración Obligatoria por provincias. Semana 13/2025 y acumulado desde la semana 01/2025. Datos provisionales. Incluye además el artículo titulado “Influencia de los determinantes sociales sobre la calidad de vida en pacientes con multimorbilidad y polifarmacia”, de “José María Ruiz-Baena, Aida Moreno-Juste, Beatriz Poblador-Plou, Marcos Castillo-Jimena, Amaia Calderón-Larrañaga, Cristina Lozano-Hernández, Antonio Gimeno-Miguel, Luis A. Gimeno-Feliú".Publication Surgical treatment for infective endocarditis in elderly patients(Elsevier, 2011-06-06) Ramirez-Duque, N.; García-Cabrera, Emilio; Ivanova-Georgieva, R.; Noureddine, Mariam; Lomas, J. M.; Hidalgo-Tenorio, Carmen; Plata, A.; Gálvez-Acebal, Juan; Ruiz-Morales, J.; de la Torre-Lima, J.; Reguera-Iglesias, José María; Martinez-Marcos, F. J.; de Alarcón, Arístides; [Ramirez-Duque,N; Garcia-Cabrera,E; Alarcon,A] Hospital Virgen del Rocio, Sevilla, Spain.; [Ivanova-Georgieva,R; Ruiz-Morales;J;] Hospital Virgen de la Victoria, Málaga, Spain.; [Noureddine,M; de la Torre-Lima,J;] Hospital Costa del Sol, Marbella, Spain.; [Lomas,JM; Martinez-Marcos,FJ] Hospital Juan Ramón Jiménez, Huelva, Spain.; [Hidalgo-Tenorio,C] Hospital Virgen de las Nieves, Granada, Spain.; [Plata,A; Reguera,JM] Hospital Carlos Haya, Malaga, Spain.; Ministerio de Sanidad y Consumo; Instituto de Salud Carlos III; Spanish Network for the Research in Infectious Diseases; Grupo para el Estudio de las Infecciones Cardiovasculares de la Sociedad Andaluza de Enfermedades Infecciosas (SAEI)Objectives: We evaluate the clinical, echographic and prognostic characteristics of infective endocarditis (IE) in a large population of elderly patients, and the results of surgical approach.Methods: Multicentric, prospective, observational cohort study with 961 consecutive left-sided IE: ;356 patients aged >= 65 years were compared with 605 younger. Indications for cardiac surgery, potential surgical risk, time and outcome, were compared.Results: Hospital-acquired endocarditis, comorbidity, renal failure and septic shock were more frequent in elderly, but embolisms were less. Intracardiac destruction and ventricular failure were similar in both groups, but significantly fewer elderly patients underwent cardiac surgery (36% vs 51%; p < 0.01), and this group showed a worse outcome (43.2% of mortality vs 27% in younger; p < 0.01), resulting age as an independent predictor of mortality (OR: 1.02 CI95%: 1.01-1.03). Compared with medical treatment, surgery showed lower percentages ofmortality compared with medical treatment (23.3% vs 31.3%; p = 0.03) in younger group, but a high mortality was observed with both procedures (47.6% vs 40.3%; p = 0.1) in the elderly.Conclusions: Although similar percentages of heart failure and intracardiac complications, increasing age is associated with higher mortality in IE. Lower rates of surgical treatment and a worse outcome after operation are common features in elderly patients.Item Phase II study of high-sensitivity genotyping of KRAS, NRAS, BRAF and PIK3CA to ultra-select metastatic colorectal cancer patients for panitumumab plus FOLFIRI: the ULTRA trial.(2019) Santos, C; Azuara, D; Viéitez, J M; Páez, D; Falcó, E; Élez, E; López-López, C; Valladares, M; Robles-Díaz, L; García-Alfonso, P; Bugés, C; Durán, G; Salud, A; Navarro, V; Capellá, G; Aranda, E; Salazar, RSeveral studies show the importance of accurately quantifying not only KRAS and other low-abundant mutations because benefits of anti-EGFR therapies may depend on certain sensitivity thresholds. We assessed whether ultra-selection of patients using a high-sensitive digital PCR (dPCR) to determine KRAS, NRAS, BRAF and PIK3CA status can improve clinical outcomes of panitumumab plus FOLFIRI. This was a single-arm phase II trial that analysed 38 KRAS, NRAS, BRAF and PIK3CA hotspots in tumour tissues of irinotecan-resistant metastatic colorectal cancer patients who received panitumumab plus FOLFIRI until disease progression or early withdrawal. Mutation profiles were identified by nanofluidic dPCR and correlated with clinical outcomes (ORR, overall response rate; PFS, progression-free survival; OS, overall survival) using cut-offs from 0% to 5%. A quantitative PCR (qPCR) analysis was also performed. Seventy-two evaluable patients were enrolled. RAS (KRAS/NRAS) mutations were detected in 23 (32%) patients and RAS/BRAF mutations in 25 (35%) by dPCR, while they were detected in 7 (10%) and 11 (15%) patients, respectively, by qPCR. PIK3CA mutations were not considered in the analyses as they were only detected in 2 (3%) patients by dPCR and in 1 (1%) patient by qPCR. The use of different dPCR cut-offs for RAS (KRAS/NRAS) and RAS/BRAF analyses translated into differential clinical outcomes. The highest ORR, PFS and OS in wild-type patients with their lowest values in patients with mutations were achieved with a 5% cut-off. We observed similar outcomes in RAS/BRAF wild-type and mutant patients defined by qPCR. High-sensitive dPCR accurately identified patients with KRAS, NRAS, BRAF and PIK3CA mutations. The optimal RAS/BRAF mutational cut-off for outcome prediction is 5%, which explains that the predictive performance of qPCR was not improved by dPCR. The biological and clinical implications of low-frequent mutated alleles warrant further investigations. NCT01704703. 2012-001955-38.Item Clinical and Ultrasound Thyroid Nodule Characteristics and Their Association with Cytological and Histopathological Outcomes: A Retrospective Multicenter Study in High-Resolution Thyroid Nodule Clinics.(2019-12-09) Molina-Vega, María; Rodríguez-Pérez, Carlos Antonio; Álvarez-Mancha, Ana Isabel; Baena-Nieto, Gloria; Riestra, María; Alcázar, Victoria; Romero-Lluch, Ana Reyes; Galofré, Juan C; Fernández-García, José CThyroid nodules are a common finding. A high-resolution thyroid nodule clinic (HR-TNC) condenses all tests required for the evaluation of thyroid nodules into a single appointment. We aimed to evaluate the clinical outcomes at HR-TNCs. A retrospective cross-sectional multicenter study including data from four HR-TNCs in Spain. We evaluated fine-needle aspiration (FNA) indications and the association between clinical and ultrasound characteristics with cytological and histopathological outcomes. A total of 2809 thyroid nodules were included; FNA was performed in 82.1%. Thyroid nodules that underwent FNA were more likely larger, isoechoic, with microcalcifications, and in younger subjects. The rate of nondiagnostic FNA was 4.3%. A solid component, irregular margins or microcalcifications, significantly increased the odds of Bethesda IV-V-VI (vs. Bethesda II). Irregular margins and a solid component were independently associated with increased odds of malignancy. Thyroid nodules In this large multicenter study, we found that the presence of a solid component and irregular margins are factors independently related to malignancy in thyroid nodules. Since nodule size ≥40 mm was associated with the lowest odds of malignancy, this cut-off should not be a factor leading to indicate thyroid surgery. HR-TNCs were associated with a low rate of nondiagnostic FNA.Item Decision Making Impairment: A Shared Vulnerability in Obesity, Gambling Disorder and Substance Use Disorders?(2016-09-30) Mallorquí-Bagué, Nuria; Fagundo, Ana B; Jimenez-Murcia, Susana; de la Torre, Rafael; Baños, Rosa M; Botella, Cristina; Casanueva, Felipe F; Crujeiras, Ana B; Fernández-García, Jose C; Fernández-Real, Jose M; Frühbeck, Gema; Granero, Roser; Rodríguez, Amaia; Tolosa-Sola, Iris; Ortega, Francisco J; Tinahones, Francisco J; Alvarez-Moya, Eva; Ochoa, Cristian; Menchón, Jose M; Fernández-Aranda, FernandoAddictions are associated with decision making impairments. The present study explores decision making in Substance use disorder (SUD), Gambling disorder (GD) and Obesity (OB) when assessed by Iowa Gambling Task (IGT) and compares them with healthy controls (HC). For the aims of this study, 591 participants (194 HC, 178 GD, 113 OB, 106 SUD) were assessed according to DSM criteria, completed a sociodemographic interview and conducted the IGT. SUD, GD and OB present impaired decision making when compared to the HC in the overall task and task learning, however no differences are found for the overall performance in the IGT among the clinical groups. Results also reveal some specific learning across the task patterns within the clinical groups: OB maintains negative scores until the third set where learning starts but with a less extend to HC, SUD presents an early learning followed by a progressive although slow improvement and GD presents more random choices with no learning. Decision making impairments are present in the studied clinical samples and they display individual differences in the task learning. Results can help understanding the underlying mechanisms of OB and addiction behaviors as well as improve current clinical treatments.Item Phosphorylated-insulin growth factor I receptor (p-IGF1R) and metalloproteinase-3 (MMP3) expression in advanced gastrointestinal stromal tumors (GIST). A GEIS 19 study.(BioMed Central, 2016-06-29) Maurel, Joan; Lopez-Pousa, Antonio; Calabuig, Silvia; Bague, Silvia; Garcia-Del-Muro, Xavier ; Sanjuan, Xavier; Rubio-Casadevall, Jordi; Cuatrecasas, Miriam; Martinez-Trufero, Javier; Horndler, Carlos; Fra, Joaquin; Valverde, Claudia; Redondo, Andres; Poveda, Andres; Sevilla, Isabel; Lainez, Nuria; Rubini, Michele; Garcia-Albeniz, Xabier; Martin-Broto, Javier; de-Alava, EnriqueMost GISTs have mutations in KIT or PDGFRA. Patients with advanced GIST with KIT exon 9, PDGFRA mutation or WT for KIT and PDGFRA have a worse progression-free survival (PFS) compared to patients with KIT exon 11 mutated tumors. We evaluated the immunohistochemical (IHC) expression of p-IGF1R (Y1316) and MMP3 as predictors of PFS or overall survival (OS). Ninety-two advanced GIST patients included in GEIS-16 study with KIT and PDGFRA mutational information were examined for p-IGF1R (Y1316) and MMP3 expression in a tissue micro-array. To study activation of the IGF1R system, we have used an antibody (anti-pY1316) that specifically recognizes the active phosphorylated form of the IGF1R. DNA was extracted from paraffin-embedded tissues and intronic PCR primers were used to amplify exons 9, 11, 13 and 17 of KIT, 12 and 18 of PDGFRA. Bidirectional sequencing with specific primers was performed on a ABI3100 sequencer using the Big Dye Terminator v3.1 kit. Multivariate model was built using a stepwise automated variable selection approach with criterion to enter the variable in the model of p Phospho-IGF1R was expressed only in 9 % (2/22) of cases without KIT mutation. MMP3 expression was detected in 2/5 patients (40 %) with PDGFRA mutation, 1/16 patients (6 %) with WT genotype and 7/71 patients (10 %) of KIT mutant patients. At univariate analysis KIT exon 11/13 mutation had better PFS than patients with exon 9 mutation, PDGFRA mutation or WT genotype (p = 0.021; HR: 0.46; 95 %CI (0.28-0.76). Less than 24 months disease free-interval (HR 24.2, 95 % CI 10.5-55.8), poor performance status (PS) (HR 6.3, 95 % CI 2.5-15.9), extension of disease; >1 organ (HR 1.89; 95 % CI 1.03-3.4) and genotype analysis (HR 0.57, 95 % CI 0.37-0.97) but not immunophenotype analysis (HR 1.53; 95 % CI 0.76-3.06) were the strongest prognostic factors for PFS in the multivariate analysis. Our results do not support p-IGF-1R and MMP3 evaluation in non-selected GIST patients but evaluation of this immunophenotype in WT and mutant PDGFR mutation in larger group of GIST patients, deserve merits.Item Update of the hyperglycemia Gestational diagnosis during the COVID-19 pandemic.(2020-05-19) Codina, Mercè; Corcoy, Rosa; Goya, María M; en representación del GEDE Consenso del Grupo Español de Diabetes y Embarazo (GEDE); GEDE Consenso del Grupo Español de Diabetes y Embarazo (GEDE)Item 21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer.(Massachusetts Medical Society, 2021-12-16) Kalinsky, Kevin; Barlow, William E; Gralow, Julie R; Meric-Bernstam, Funda; Albain, Kathy S; Hayes, Daniel F; Lin, Nancy U; Perez, Edith A; Goldstein, Lori J; Chia, Stephen K L; Dhesy-Thind, Sukhbinder; Rastogi, Priya; Alba, Emilio; Delaloge, Suzette; Martin, Miguel; Kelly, Catherine M; Ruiz-Borrego, Manuel; Gil-Gil, Miguel; Arce-Salinas, Claudia H; Brain, Etienne G C; Lee, Eun-Sook; Pierga, Jean-Yves; Bermejo, Begoña; Ramos-Vazquez, Manuel; Jung, Kyung-Hae; Ferrero, Jean-Marc; Schott, Anne F; Shak, Steven; Sharma, Priyanka; Lew, Danika L; Miao, Jieling; Tripathy, Debasish; Pusztai, Lajos; Hortobagyi, Gabriel NThe recurrence score based on the 21-gene breast-cancer assay has been clinically useful in predicting a chemotherapy benefit in hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, axillary lymph-node-negative breast cancer. In women with positive lymph-node disease, the role of the recurrence score with respect to predicting a benefit of adjuvant chemotherapy is unclear. In a prospective trial, we randomly assigned women with hormone-receptor-positive, HER2-negative breast cancer, one to three positive axillary lymph nodes, and a recurrence score of 25 or lower (scores range from 0 to 100, with higher scores indicating a worse prognosis) to endocrine therapy only or to chemotherapy plus endocrine (chemoendocrine) therapy. The primary objective was to determine the effect of chemotherapy on invasive disease-free survival and whether the effect was influenced by the recurrence score. Secondary end points included distant relapse-free survival. A total of 5083 women (33.2% premenopausal and 66.8% postmenopausal) underwent randomization, and 5018 participated in the trial. At the prespecified third interim analysis, the chemotherapy benefit with respect to increasing invasive disease-free survival differed according to menopausal status (P = 0.008 for the comparison of chemotherapy benefit in premenopausal and postmenopausal participants), and separate prespecified analyses were conducted. Among postmenopausal women, invasive disease-free survival at 5 years was 91.9% in the endocrine-only group and 91.3% in the chemoendocrine group, with no chemotherapy benefit (hazard ratio for invasive disease recurrence, new primary cancer [breast cancer or another type], or death, 1.02; 95% confidence interval [CI], 0.82 to 1.26; P = 0.89). Among premenopausal women, invasive disease-free survival at 5 years was 89.0% with endocrine-only therapy and 93.9% with chemoendocrine therapy (hazard ratio, 0.60; 95% CI, 0.43 to 0.83; P = 0.002), with a similar increase in distant relapse-free survival (hazard ratio, 0.58; 95% CI, 0.39 to 0.87; P = 0.009). The relative chemotherapy benefit did not increase as the recurrence score increased. Among premenopausal women with one to three positive lymph nodes and a recurrence score of 25 or lower, those who received chemoendocrine therapy had longer invasive disease-free survival and distant relapse-free survival than those who received endocrine-only therapy, whereas postmenopausal women with similar characteristics did not benefit from adjuvant chemotherapy. (Funded by the National Cancer Institute and others; RxPONDER ClinicalTrials.gov number, NCT01272037.).Item Clinical utility of plasma-based digital next-generation sequencing in patients with advance-stage lung adenocarcinomas with insufficient tumor samples for tissue genotyping.(2019) Zugazagoitia, J; Ramos, I; Trigo, J M; Palka, M; Gómez-Rueda, A; Jantus-Lewintre, E; Camps, C; Isla, D; Iranzo, P; Ponce-Aix, S; García-Campelo, R; Provencio, M; Franco, F; Bernabé, R; Juan-Vidal, O; Felip, E; de Castro, J; Sanchez-Torres, J M; Faul, I; Lanman, R B; Garrido, P; Paz-Ares, LApproximately 30% of tumor biopsies from patients with advanced-stage lung adenocarcinomas yield insufficient tissue for successful molecular subtyping. We have analyzed the clinical utility of next-generation sequencing (NGS) of cell-free circulating tumor DNA (ctDNA) in patients with inadequate tumor samples for tissue genotyping. We conducted the study in a multi-institutional prospective cohort of clinically unselected patients with advanced-stage lung adenocarcinomas with insufficient tissue for EGFR, ALK or ROS1 genotyping across 12 Spanish institutions (n = 93). ctDNA NGS was carried out by Guardant Health (Guardant360, Redwood City, CA), using a hybrid-capture-based 73-gene panel. Variants were deemed actionable if they were part of the OncoKB precision oncology knowledge database and classified in four levels of actionability based on their clinical or preclinical evidence for drug response. Eighty-three out of 93 patients (89%) had detectable levels of ctDNA. Potentially actionable level 1-4 genomic alterations were detected in 53 cases (57%), of which 13 (14%) had level 1-2A alterations (Food and Drug Administration-approved and standard-care biomarkers according to lung cancer guidelines). Frequencies of each genomic alteration in ctDNA were consistent with those observed in unselected pulmonary adenocarcinomas. The majority of the patients (62%), particularly those with actionable alterations (87%), had more than one pathogenic variant in ctDNA. The median turnaround time to genomic results was 13 days. Twelve patients (13%) received genotype-matched therapies based on ctDNA results, deriving the expected clinical benefit. Patients with co-occurring pathogenic alterations had a significantly shorter median overall survival as compared with patients without co-occurring pathogenic alteration (multivariate hazard ratio = 5.35, P = 0.01). Digital NGS of ctDNA in lung cancers with insufficient tumor samples for tissue sequencing detects actionable variants that frequently co-occur with other potentially clinically relevant genomic alterations, allowing timely initiation of genotype-matched therapies.Item Adverse prognostic impact of complex karyotype (≥3 cytogenetic alterations) in adult T-cell acute lymphoblastic leukemia (T-ALL).(2021-06-08) Genescà, Eulàlia; Morgades, Mireia; González-Gil, Celia; Fuster-Tormo, Francisco; Haferlach, Claudia; Meggendorfer, Manja; Montesinos, Pau; Barba, Pere; Gil, Cristina; Coll, Rosa; Moreno, María-José; Martínez-Carballeira, Daniel; García-Cadenas, Irene; Vives, Susana; Ribera, Jordi; González-Campos, José; Díaz-Beya, Marina; Mercadal, Santiago; Artola, María-Teresa; Cladera, Antonia; Tormo, Mar; Bermúdez, Arancha; Vall-Llovera, Ferran; Martínez-Sánchez, Pilar; Amigo, María-Luz; Monsalvo, Silvia; Novo, Andrés; Cervera, Marta; García-Guiñon, Antonio; Ciudad, Juana; Cervera, José; Hernández-Rivas, Jesús-María; Granada, Isabel; Haferlach, Torsten; Orfao, Alberto; Solé, Francesc; Ribera, Josep-MariaThe potential prognostic value of conventional karyotyping in adult T-cell acute lymphoblastic leukemia (T-ALL) remains an open question. We hypothesized that a modified cytogenetic classification, based on the number and type of cytogenetic abnormalities, would allow the identification of high-risk adult T-ALL patients. Complex karyotype defined by the presence of ≥3 cytogenetic alterations identified T-ALL patients with poor prognosis in this study. Karyotypes with ≥3 abnormalities accounted for 16 % (22/139) of all evaluable karyotypes, corresponding to the largest poor prognosis cytogenetic subgroup of T-ALL identified so far. Patients carrying karyotypes with ≥3 cytogenetic alterations showed a significantly inferior response to therapy, and a poor outcome in terms of event-free survival (EFS), overall survival (OS) and cumulative incidence of relapse (CIR), independently of other baseline characteristics and the end-induction minimal residual disease (MRD) level. Additional molecular analyses of patients carrying ≥3 cytogenetic alterations showed a unique molecular profile that could contribute to understand the underlying molecular mechanisms of resistance and to evaluate novel targeted therapies (e.g. IL7R directed) with potential impact on outcome of adult T-ALL patients.Item PATTERNS OF INTERSTITIAL LUNG DISEASE IN RHEUMATOID ARTHRITIS AND ABATACEPT. MULTICENTER STUDY OF 63 PATIENTS(Bmj publishing group, 2017-06-01) Fernandez-Diaz, C.; Castaneda, S.; Ojeda, C.; Olive, A.; Carreira, P.; Perez-Sandoval, T.; Retuerto, M.; Cervantes, E.; Rodriguez, S.; Robles, B.; Hernandez, B.; Urruticoechea, A.; Maiz, O.; Palma, D.; Arboleya, L.; Bonilla, G.; Rodriguez, I.; Delgado, C.; Exposito, R.; Ruibal, A.; Blanco, J.; Rodriguez, M.; Bernal, J.; Vela, P.; Alvarez, B.; Fito, C.; Narvaez, J.; Moreno, M.; Lopez, M.; Mena, N.; Romero, S.; Aguilera, C.; Ordonez, S.; Villa, I.; Mora, V.; Gonzalez-Gay, M.; Hernandez, J.; Blanco, R.; [Fernandez-Diaz, C.] HUMV, Santander, Spain; [Mora, V.] HUMV, Santander, Spain; [Gonzalez-Gay, M.] HUMV, Santander, Spain; [Hernandez, J.] HUMV, Santander, Spain; [Blanco, R.] HUMV, Santander, Spain; [Castaneda, S.] Hosp Princesa, Madrid, Spain; [Ojeda, C.] Hosp Macarena, Seville, Spain; [Hernandez, B.] Hosp Macarena, Seville, Spain; [Olive, A.] Hosp Trias, Barcelona, Spain; [Rodriguez, S.] Hosp Trias, Barcelona, Spain; [Carreira, P.] Hosp 12 Octubre, Madrid, Spain; [Perez-Sandoval, T.] Hosp Leon, Leon, Spain; [Retuerto, M.] Hosp Leon, Leon, Spain; [Cervantes, E.] Hosp Santiago, Santiago, Spain; [Robles, B.] Hosp P Hierro, Madrid, Spain; [Urruticoechea, A.] Hosp Ibiza, Ibiza, Spain; [Maiz, O.] Hosp Donostia, Donostia San Sebastian, Spain; [Palma, D.] Hosp Lorca, Lorca, Spain; [Arboleya, L.] Hosp Oviedo, Oviedo, Spain; [Bonilla, G.] Hosp Paz, Madrid, Spain; [Rodriguez, I.] Hosp Vigo, Vigo, Spain; [Delgado, C.] Hosp Zaragoza, Zaragoza, Spain; [Exposito, R.] Hosp Laredo, Laredo, Spain; [Ruibal, A.] Hosp Araba, Araba, Spain; [Alvarez, B.] Hosp Araba, Araba, Spain; [Blanco, J.] Hosp Basurto, Bilbao, Spain; [Rodriguez, M.] Hosp Ourense, Orense, Spain; [Bernal, J.] Hosp Alicante, Alicante, Spain; [Vela, P.] Hosp Alicante, Alicante, Spain; [Fito, C.] Hosp Pamplona, Pamplona, Spain; [Narvaez, J.] Hosp Bellvitge Princeps Espanya, Barcelona, Spain; [Moreno, M.] Hosp Arrixaca, Murcia, Spain; [Lopez, M.] HVHebron, Barcelona, Spain; [Mena, N.] Hosp Malaga, Malaga, Spain; [Romero, S.] Hosp Pontevedra, Pontevedra, Spain; [Aguilera, C.] Hosp Sevilla, Seville, Spain; [Ordonez, S.] Hosp Lleida, Lleida, Spain; [Villa, I.] Hosp Sierrallana, Sierrallana, SpainItem Inducible T cell co-stimulatory (ICOS) receptor agonist, GSK3359609 (GSK609) alone and combination with pembrolizumab: Preliminary results from INDUCE-1 expansion cohorts in head and neck squamous cell carcinoma (HNSCC)(Oxford univ press, 2020-03-01) Le Tourneau, C.; Rischin, D.; Groenland, S.; Lim, A.; Martin-Liberal, J.; Moreno, V.; Trigo, J. M.; Mathew, M.; Cho, D.; Hansen, A.; Baz, D. Vincente; Maio, M.; Italiano, A.; Bauman, J.; Chisamore, M.; Zhou, H.; Ellis, C.; Ballas, M.; Hoos, A.; Angevin, E.; [Le Tourneau, C.] Inst Curie, Paris, France; [Rischin, D.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia; [Rischin, D.] Univ Melbourne, Melbourne, Vic, Australia; [Groenland, S.] Netherlands Canc Inst, Antoni van Leeuwenhoek, Amsterdam, Netherlands; [Lim, A.] Linear Clin Res & Sir Charles Gairdner Hosp, Nedlands, WA, Australia; [Martin-Liberal, J.] Vall dHebron Inst Oncol VHIO Cellex Cente, Barcelona, Spain; [Moreno, V.] Univ Hosp Fdn Jimenez Diaz, START Madrid FJD, Madrid, Spain; [Trigo, J. M.] Hosp Univ Virgen Victoria, Malaga, Spain; [Mathew, M.] Columbia Univ, Med Ctr, New York, NY USA; [Cho, D.] NYU, Langone Med Ctr, New York, NY USA; [Hansen, A.] Princess Margaret Canc Ctr, Toronto, ON, Canada; [Baz, D. Vincente] Hosp Univ Virgen Macarena, Seville, Spain; [Maio, M.] Univ Hosp Siena, Siena, Italy; [Italiano, A.] Inst Bergonie, Bordeaux, France; [Bauman, J.] Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA; [Chisamore, M.] Merck & Co Inc, N Wales, PA USA; [Zhou, H.] GSK, Collegeville, PA USA; [Ellis, C.] GSK, Collegeville, PA USA; [Ballas, M.] GSK, Collegeville, PA USA; [Hoos, A.] GSK, Collegeville, PA USA; [Angevin, E.] Gustave Roussy Inst Cancerol, Villejuif, France; GlaxoSmithKline (GSK); Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USAItem Use of the Bruininks-Oseretsky test of motor proficiency (BOT-2) to assess efficacy of velmanase alfa as enzyme therapy for alpha-mannosidosis.(2020-04-08) Phillips, Dawn; Hennermann, Julia B; Tylki-Szymanska, Anna; Borgwardt, Line; Gil-Campos, Mercedes; Guffon, Nathalie; Amraoui, Yasmina; Geraci, Silvia; Ardigò, Diego; Cattaneo, Federica; Lund, Allan MAlpha-mannosidosis is a rare autosomal recessive lysosomal storage disorder resulting from deficient lysosomal alpha-mannosidase activity. Clinical manifestations include progressive balance disorders, immune deficiency, skeletal abnormalities and cognitive deficits beginning in early childhood. Enzyme replacement therapy with recombinant human alpha-mannosidase (velmanase alfa) is scheduled for clinical development in the US beginning in 2020 and has been approved in the EU for treatment of non-neurological manifestations in cases of mild to moderate disease. This study assessed effects of velmanase alfa on fine and gross motor proficiency in children and adults. Integrated Bruininks-Oseretsky (BOT-2) test of Motor Proficiency data from velmanase alfa clinical trials was stratified by age for 14 adults and 19 children treated for up to 4 years. Patients showed global developmental delays at baseline. For the combined adult and pediatric group there was a statistically significant increase (improvement) in BOT-2 total point score of 13% (p = .035, 95% CI 1.0, 25.0) from baseline to last observation. When stratified by pediatric versus adult patients, there was improvement in BOT-2 total point score in patients There was limited ability to assess the BOT-2 change responses in adults. Pediatric patients showed stability or improvement in scaled scores relative to healthy peers, indicating continued skill acquisition, which may increase independence and contribute to improved patient quality of life.Item Weaning practices in phenylketonuria vary between health professionals in Europe.(2018-11-25) Pinto, A; Adams, S; Ahring, K; Allen, H; Almeida, M F; Garcia-Arenas, D; Arslan, N; Assoun, M; Atik Altınok, Y; Barrio-Carreras, D; Belanger Quintana, A; Bernabei, S M; Bontemps, C; Boyle, F; Bruni, G; Bueno-Delgado, M; Caine, G; Carvalho, R; Chrobot, A; Chyż, K; Cochrane, B; Correia, C; Corthouts, K; Daly, A; De Leo, S; Desloovere, A; De Meyer, A; De Theux, A; Didycz, B; Dijsselhof, M E; Dokoupil, K; Drabik, J; Dunlop, C; Eberle-Pelloth, W; Eftring, K; Ekengren, J; Errekalde, I; Evans, S; Foucart, A; Fokkema, L; François, L; French, M; Forssell, E; Gingell, C; Gonçalves, C; Gökmen Özel, H; Grimsley, A; Gugelmo, G; Gyüre, E; Heller, C; Hensler, R; Jardim, I; Joost, C; Jörg-Streller, M; Jouault, C; Jung, A; Kanthe, M; Koç, N; Kok, I L; Kozanoğlu, T; Kumru, B; Lang, F; Lang, K; Liegeois, I; Liguori, A; Lilje, R; Ļubina, O; Manta-Vogli, P; Mayr, D; Meneses, C; Newby, C; Meyer, U; Mexia, S; Nicol, C; Och, U; Olivas, S M; Pedrón-Giner, C; Pereira, R; Plutowska-Hoffmann, K; Purves, J; Re Dionigi, A; Reinson, K; Robert, M; Robertson, L; Rocha, J C; Rohde, C; Rosenbaum-Fabian, S; Rossi, A; Ruiz, M; Saligova, J; Gutiérrez-Sánchez, A; Schlune, A; Schulpis, K; Serrano-Nieto, J; Skarpalezou, A; Skeath, R; Slabbert, A; Straczek, K; Giżewska, M; Terry, A; Thom, R; Tooke, A; Tuokkola, J; van Dam, E; van den Hurk, T A M; van der Ploeg, E M C; Vande Kerckhove, K; Van Driessche, M; van Wegberg, A M J; van Wyk, K; Vasconcelos, C; Velez García, V; Wildgoose, J; Winkler, T; Żółkowska, J; Zuvadelli, J; MacDonald, AIn phenylketonuria (PKU), weaning is considered more challenging when compared to feeding healthy infants. The primary aim of weaning is to gradually replace natural protein from breast milk or standard infant formula with solids containing equivalent phenylalanine (Phe). In addition, a Phe-free second stage L-amino acid supplement is usually recommended from around 6 months to replace Phe-free infant formula. Our aim was to assess different weaning approaches used by health professionals across Europe. A cross sectional questionnaire (survey monkey®) composed of 31 multiple and single choice questions was sent to European colleagues caring for inherited metabolic disorders (IMD). Centres were grouped into geographical regions for analysis. Weaning started at 17-26 weeks in 85% (n = 81/95) of centres, >26 weeks in 12% (n = 11/95) and 26 weeks in 12% (n = 11/95) and 26 weeks. First solids were mainly low Phe vegetables (59%, n = 56/95) and fruit (34%, n = 32/95).A Phe exchange system to allocate dietary Phe was used by 52% (n = 49/95) of centres predominantly from Northern and Southern Europe and 48% (n = 46/95) calculated most Phe containing food sources (all centres in Eastern Europe and the majority from Germany and Austria). Some centres used a combination of both methods.A second stage Phe-free L-amino acid supplement containing a higher protein equivalent was introduced by 41% (n = 39/95) of centres at infant age 26-36 weeks (mainly from Germany, Austria, Northern and Eastern Europe) and 37% (n = 35/95) at infant age > 1y mainly from Southern Europe. 53% (n = 50/95) of centres recommended a second stage Phe-free L-amino acid supplement in a spoonable or semi-solid form. Weaning strategies vary throughout European PKU centres. There is evidence to suggest that different infant weaning strategies may influence longer term adherence to the PKU diet or acceptance of Phe-free L-amino acid supplements; rendering prospective long-term studies important. It is essential to identify an effective weaning strategy that reduces caregiver burden but is associated with acceptable dietary adherence and optimal infant feeding development.