Search

No description supplied

Background: Covid-19 pandemic by the new coronavirus SARS-Cov-2 has produced devastating effects on the health care system, affecting also cancer patient care. Data about COVID-19 infection in cancer patients are scarce, and they point out a higher risk of complications due to the viral infection in this population. Moreover, cancer treatments could increase viral complications, specially those treatments based on the use of immunotherapy with checkpoints antibodies. There are no clinical data about the safety of immune check point antibodies in cancer patients when they become infected by SARS-CoV-2. As checkpoint inhibitors, mainly anti PD-1 and anti CTLA-4 antibodies, are an effective treatment for most melanoma patients, avoiding their use during the pandemic could lead to a decrease in the chances of curing melanoma. Methods: In Spain we have started a national registry of melanoma patients infected by SARS-Cov-2 since April 1st, 2020. A retrospective analysis of patients included in the Spanish registery has been performed weekly since the activation of the study. Interim analysis shows unexpected findings about cancer treatment safety in SARS-Cov-2 infected melanoma patients, so a rapid communication to the scientific community is mandatory Results: Fifty patients have been included as of May 17th, 2020. Median age is 69 years (range 6 to 94 years), 27 (54%) patients are males and 36 (70%) patients have stage IV melanoma. Twenty-two (44%) patients were on active anticancer treatment with anti PD-1 antibodies, 16 (32%) patients were on treatment with BRAF plus MEK inhibitors and 12 (24%) patients were not on active cancer treatment. COVID-19 episode has been resolved in 43 cases, including 30 (70%) patients cured, four (9%) patients that have died due to melanoma progression, and nine (21%) patients that have died from COVID-19. Mortality rates from COVID-19 according to melanoma treatment type were 16%, 15% and 36% for patients on immunotherapy, targeted drugs, and for those that were not undergoing active cancer treatment, respectively. Conclusion: These preliminary findings show that the risk of death in those patients undergoing treatment with anti PD-1 antibodies does not exceed the global risk of death in this population. These results could be relevant in order to select melanoma therapy during the COVID-19 pandemic

Background: Cemiplimab is a programmed cell death receptor-1 inhibitor with antitumour activity for cutaneous squamous cell carcinoma (CSCC) and acceptable safety proved in its pivotal trial. We provide the first data on cemiplimab safety in daily practice from the named patient programme (NPP) for advanced CSCC in Spain. Methods: This cemiplimab NPP was performed from March 2019 to March 2020. It included patients aged ≥18 years with advanced CSCC and ineligible for surgery, radiation therapy or clinical trials. The cemiplimab safety was assessed according to treatment-emergent adverse events (TEAEs) reported until March 2021. Results: 140 patients were included (median age [interquartile range, IQR] 77.0 [65.0-84.0] years;age ≥80 38%;men 71.7%;≥1 comorbidity 83%;ECOG 0-1 86.3%;locally advanced CSCC 60.7%;cemiplimab as first-line therapy 67.7%). Cemiplimab was received for a median (IQR) of 8.0 (3.0-14.0) cycles. Fifty-eight (41.4%) patients showed ≥1 of the 163 TEAEs reported, which most frequently included diarrhoea n=7, asthenia n=6, constipation n=4 and abdominal pain n=4. Fourteen (8.6%) were immune-mediated, mainly bronchitis n=2, pneumonitis n=2 and hepatitis n=2. Seventy-eight (47.9%) TEAEs were grade ≥3, most frequently pneumonia n=3, COVID-19 n=3, general physical health deterioration n=2, pyrexia n=2, renal transplant failure n=2, sepsis n=2, acute kidney injury n=2 and respiratory failure n=2. Twenty-one (12.9%) were treatment-related (TREAEs): 11 (6.7%) were grade 1-2 (diarrhoea n=3 and asthenia, hepatotoxicity, malnutrition, odynophagia, polymyalgia rheumatica, pneumonitis, pruritus, and skin toxicity), 9 (5.5%) grade 3 (acute kidney injury, adrenal insufficiency, abdominal pain, blood creatinine increased, dysphagia, haematuria, immune-mediated enterocolitis, panniculitis, surgical wound infection) and 1 (0.6%) unknown grade. Cemiplimab was withdrawn due to TREAEs in only 5 (3.6%) patients. The TEAE outcome was fatal in 29 (17.8%);none related to cemiplimab. Conclusions: This NPP supports the real-life safety of cemiplimab for CSCC, showing an acceptable safety profile consistent with previous reports. Editorial acknowledgement: Editorial assistance was provided by Esther Alvarez-Garcia at Dynamic Science S.L., funded by Sanofi. Legal entity responsible for the study: Sanofi. Funding: Sanofi. Disclosure: E. Munoz Couselo: Financial Interests, Personal, Advisory Board: Amgen;Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb;Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme;Financial Interests, Personal, Advisory Board: Novartis;Financial Interests, Personal, Advisory Board: Pierre Fabre;Financial Interests, Personal, Advisory Board: Roche;Financial Interests, Personal, Advisory Board: Sanofi;Financial Interests, Personal, Other, Honoraria: Amgen;Financial Interests, Personal, Other, Honoraria: Bristol-Myers Squibb;Financial Interests, Personal, Other, Honoraria: Merck Sharp & Dohme;Financial Interests, Personal, Other, Honoraria: Novartis;Financial Interests, Personal, Other, Honoraria: Pierre Fabre;Financial Interests, Personal, Other, Honoraria: Roche;Financial Interests, Personal, Principal Investigator: Amgen;Financial Interests, Personal, Principal Investigator: Bristol-Myers Squibb;Financial Interests, Personal, Principal Investigator: GlaxoSmithKline;Financial Interests, Personal, Principal Investigator: Merck Sharp & Dohme;Financial Interests, Personal, Principal Investigator: Novartis;Financial Interests, Personal, Principal Investigator: Pierre Fabre;Financial Interests, Personal, Principal Investigator: Roche;Financial Interests, Personal, Principal Investigator: Sanofi. A. Soria: Financial Interests, Personal, Invited Speaker: Novartis;Financial Interests, Personal, Invited Speaker: Sanofi Aventis;Financial Interests, Personal, Invited Speaker: Roche Pharma;Financial Interests, Personal, Invited Speaker: Merck Serono;Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme;Financial Interests, Perso al, Invited Speaker: Bristol-Myers Squibb;Financial Interests, Personal, Invited Speaker: Pierre Fabre;Financial Interests, Personal, Advisory Board: Novartis;Financial Interests, Personal, Advisory Board: Sanofi Aventis;Financial Interests, Personal, Advisory Board: Roche Pharma;Financial Interests, Personal, Advisory Board: Merck Serono;Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme;Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb;Financial Interests, Personal, Advisory Board: Pierre Fabre;Financial Interests, Personal, Principal Investigator: Novartis;Financial Interests, Personal, Principal Investigator: Sanofi Aventis;Financial Interests, Personal, Principal Investigator: Roche Pharma;Financial Interests, Personal, Principal Investigator: Merck Serono;Financial Interests, Personal, Principal Investigator: Merck Sharp & Dohme;Financial Interests, Personal, Principal Investigator: Bristol-Myers Squibb;Financial Interests, Personal, Principal Investigator: Pierre Fabre. O. Sanmartin: Financial Interests, Personal, Invited Speaker: Sanofi Genzyme;Financial Interests, Personal, Advisory Board: Sanofi Genzyme;Financial Interests, Personal, Officer: Sanofi Genzyme;Financial Interests, Personal, Principal Investigator: Sanofi Genzyme;Financial Interests, Personal, Invited Speaker: Roche Pharma;Financial Interests, Personal, Advisory Board: Roche Pharma;Financial Interests, Personal, Officer: Roche Pharma;Financial Interests, Personal, Principal Investigator: Roche Pharma. J. Canueto: Financial Interests, Personal, Invited Speaker: Hoffman-La Roche;Financial Interests, Personal, Invited Speaker: Sanofi-Genzyme;Financial Interests, Personal, Invited Speaker: AbbVie;Financial Interests, Personal, Invited Speaker: LeoPharma;Financial Interests, Personal, Other, Consultancy: Sanofi-Genzyme;Financial Interests, Personal, Other, Consultancy: InflaRx;Financial Interests, Personal, Other, Consultancy: Almirall. S. Bea Ardebol: Financial Interests, Personal, Invited Speaker: Meda;Financial Interests, Personal, Advisory Board: Sanofi;Financial Interests, Personal, Advisory Board: SunPharma;Financial Interests, Personal, Other, Trial subinvestigator: Sanofi Aventis;Financial Interests, Personal, Other, Trial subinvestigator: SunPharma;Financial Interests, Personal, Other, Trial subinvestigator: PellePharma. R. Fernandez-de-Misa Cabrera: Financial Interests, Personal, Advisory Board: Sanofi. A.J. Cunquero-Tomas: Financial Interests, Personal, Invited Speaker: BMS;Financial Interests, Personal, Invited Speaker: Pierre-Fabre;Financial Interests, Personal, Writing Engagements: Sanofi;Financial Interests, Personal, Other, 2021 EADO/WMC Congress inscription fee: Sanofi. L. Fernandez Franco: Non-Financial Interests, Personal, Invited Speaker: Merck;Non-Financial Interests, Personal, Invited Speaker: Sanofi;Non-Financial Interests, Personal, Invited Speaker: Servier. I. Romero: Financial Interests, Personal, Invited Speaker: Pharmamar;Financial Interests, Personal, Invited Speaker: Roche;Financial Interests, Personal, Invited Speaker: GSK;Financial Interests, Personal, Invited Speaker: Clovis;Financial Interests, Personal, Invited Speaker: AstraZeneca;Financial Interests, Personal, Advisory Board: Pharmamar;Financial Interests, Personal, Advisory Board: Roche;Financial Interests, Personal, Advisory Board: GSK;Financial Interests, Personal, Advisory Board: Clovis;Financial Interests, Personal, Advisory Board: AstraZeneca. J. Medina Martinez: Non-Financial Interests, Personal, Invited Speaker: Roche;Non-Financial Interests, Personal, Speaker’s Bureau: Roche;Non-Financial Interests, Personal, Advisory Board: Roche;Non-Financial Interests, Personal, Invited Speaker: Novartis;Non-Financial Interests, Personal, Speaker’s Bureau: Novartis;Non-Financial Interests, Personal, Advisory Board: Novartis;Non-Financial Interests, Personal, Invited Speaker: BMS;Non-Financial Interests, Personal, Speaker’s Bureau: BMS;Non-Financial Interests, Personal, Ad isory Board: BMS;Non-Financial Interests, Personal, Invited Speaker: MSD;Non-Financial Interests, Personal, Speaker’s Bureau: MSD;Non-Financial Interests, Personal, Invited Speaker: Pierre Fabre;Non-Financial Interests, Personal, Speaker’s Bureau: Pierre Fabre;Non-Financial Interests, Personal, Advisory Board: Pierre Fabre;Non-Financial Interests, Personal, Invited Speaker: Merk;Non-Financial Interests, Personal, Speaker’s Bureau: Merk;Non-Financial Interests, Personal, Invited Speaker: Sanofi;Non-Financial Interests, Personal, Speaker’s Bureau: Sanofi;Non-Financial Interests, Personal, Advisory Board: Sanofi;Non-Financial Interests, Personal, Invited Speaker: Servier. All other authors have declared no conflicts of interest.

An automated valet parking (AVP) service which vehicles drive and park by itself is presented in this paper. Seamless integration of subsystems such as parking management system, Internet of Things (IoT) platforms, automated driving vehicles, micro-aerial-vehicle and road-side cameras provided by different stakeholders to a working solution is aided by introduction of IoT to the core of the system design. Technical realization of the AVP service with its architectural components and interacting subsystems are explained in the paper. Piloting and testing activities carried out to validate the system prove the merits of the proposed solution.

Background. Mutations in hepatocyte nuclear factor 1B (HNF1B) have been associated with congenital anomalies of the kidney and urinary tract (CAKUT) in humans. Diabetes and other less frequent anomalies have also been described. Variable penetrance and intrafamilial variability have been demonstrated including severe prenatal phenotypes. Thus, it is important to differentiate this entity from others with similar clinical features and perform confirmatory molecular diagnosis. Methods. This study reports the results of HNF1B screening in a cohort of 60 patients from 58 unrelated families presenting with renal structural anomalies and/or non-immune glucose metabolism alterations, and other minor features suggesting HNF1B mutations. Results. This study identified a pathogenic variant in 23 patients from 21 families. The most frequent finding was bilateral cystic dysplasia or hyperechogenic kidneys (87% of patients). Sixty percent of them also fulfilled the criteria for impaired glucose metabolism, and these were significantly older than those patients with an HNF1B mutation but without diabetes or prediabetes (14.4 versus 3.3 years, P < 0.05). Furthermore, patients with HNF1B mutations had higher frequency of pancreatic structural anomalies and hypomagnesaemia than patients without mutations (P < 0.001 and P = 0.003, respectively). Hyperuricaemia and increased liver enzymes were detected in some patients as well. Conclusions. Renal anomalies found in patients with HNF1B mutations are frequently unspecific and may resemble those found in other renal pathologies (CAKUT, ciliopathies). Active searching for extrarenal minor features, especially pancreatic structural anomalies or hypomagnesaemia, could support the indication for molecular diagnosis to identify HNF1B mutations.

Background LIPI, based on derived NLR (neutrophils/(leucocytes-neutrophils)) and lactate dehydrogenase (LDH) level, has been correlated to ICI outcomes in advanced non small cell lung cancer. We evaluated if HN-LIPI could offer the same role in R/M SCCHN. Methods This is a multicentric (9 European centers) retrospective study including R/M SCCHN patients (pts) treated with ICI from September 2014 to May 2019 and a control cohort (N = 83) only treated with chemotherapy. Baseline biological and clinicaldata were collected from medical records. According to dNLR>3 and LDH > upper limit of normal, HN-LIPI defines 3 groups (Good: 0 factor; Intermediate: 1 factor; Poor: 2 factors).The primary endpoint was overall survival (OS), and secondary endpoints was progression free survival (PFS). Results We included 273 pts (84% male, 84% smokers and 87% with PS ≤ 1, median age 59 years). Primary tumor locations were: oropharynx (37%), oral cavity (23%) and hypopharynx (17%). p16by immunohistochemistry was positive in 33% oropharynx pts. ICI were administered in 53% of patients as monotherapy and in 47% in combination. The median number of prior lines was 2 (1-7) with 65% of pts receiving ≥2. Median follow up of 13.2 months (mo).The median (m) PFS and OS were 2.84 mo [2.53-3.52] and 11.8mo [9.4-15.8]. dNLR >3 was associated to poor OS(HR 1.6, 95%CI: 1.1-2.3) but not with PFS (p = 0.11). LDH was not associated with endpoints. Median OS for good, intermediate and poor LIPI groups were: 15.9mo, 8.9mo and 6.2mo, respectively (p=.03). In univariate analysis, Intermediate and Poor risk groups were associated with OS (HR:1.5 95%CI:1.1-2.2 and HR:2 95%CI:1.0-4. respectively ). There was trend to better objective response rate in the good risk group compared with intermediate and poor (36%, 22% and 18%, p = 0.09). Conclusions Baseline HN-LIPI is associated with worse OS for ICI in R/M SCCHN but not with PFS. Control cohort results and multivariate models will be further presented at the congress, which would elucidate the prognostic and/or predictive impact in R/M SCCHN population. Legal entity responsible for the study Neus Baste. Funding Has not received any funding. Disclosure V. Cristina: Advisory / Consultancy: Merck-Serono; Advisory / Consultancy: Ely Lilly; Advisory / Consultancy: Servier; Advisory / Consultancy: Celgene; Travel / Accommodation / Expenses: Bayer; Travel / Accommodation / Expenses: Merck-Serono. A. Garcia Castano: Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: MSD; Advisory / Consultancy: BMS; Advisory / Consultancy: Pierre Fabre; Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: Pierre Fabre. R. Mesia Nin: Advisory / Consultancy: Merck; Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: Nanobiotix; Speaker Bureau / Expert testimony: Merck; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: MSD. M. Taberna: Non-remunerated activity/ies: Merck Serono; Non-remunerated activity/ies: AstraZeneca; Travel / Accommodation / Expenses: Merck Serono; Travel / Accommodation / Expenses: Nanobiotics; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: Bristol-Myers. B. Besse: Travel / Accommodation / Expenses: AbbVie; Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Biogen; Travel / Accommodation / Expenses: Blueprint Medicine; Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: Celgene; Travel / Accommodation / Expenses: Eli Lilly; Travel / Accommodation / Expenses: GSK; Travel / Accommodation / Expenses: Ignyta; Travel / Accommodation / Expenses: IPSEN; Travel / Accommodation / Expenses: MERCK; Travel / Accommodation / Expenses: KGaA; Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: Nektar; Travel / Accommodation / Expenses: Onxeo; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Pharma Mar; Travel / Accommodation / Expenses: SANOFI; Travel / Accommodation / Expenses: Spectrum pharmaceuticals; Travel / Accommodation / Expenses: Tiziana Pharma; Travel / Accommodation / Expenses: Takeda. N. Baste-Rotllan: Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Serono; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Nanobiotics; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: MSD. All other authors have declared no conflicts of interest.

Objective Monogenic diabetes can be misdiagnosed as type 1 or type 2 diabetes in children. The right diagnosis is crucial for both therapeutic choice and prognosis and influences genetic counseling. The main objective of this study was to search for monogenic diabetes in Spanish pediatric patients suspected of type 1 diabetes with lack of autoimmunity at the onset of the disease. We also evaluated the extra value of ZnT8A in addition to the classical IAA, GADA and IA2A autoantibodies to improve the accuracy of type 1 diabetes diagnosis. Methods Four hundred Spanish pediatric patients with recent-onset diabetes (mean age 8.9 +/- 3.9 years) were analyzed for IAA, GADA, IA2A and ZnT8A pancreatic-autoantibodies and HLA-DRB1 alleles. Patients without autoimmunity and those with only ZnT8A positive were screened for 12 monogenic diabetes genes by next generation sequencing. Results ZnT8A testing increased the number of autoantibody-positive patients from 373 (93.3%) to 377 (94.3%). An isolated positivity for ZnT8A allowed diagnosing autoimmune diabetes in 14.8% (4/27) of pediatric patients negative for the rest of the antibodies tested. At least 2 of the 23 patients with no detectable autoimmunity (8%) carried heterozygous pathogenic variants: one previously reported missense variant in the INS gene (p.Gly32Ser) and one novel frameshift variant (p.Val264fs) in the HNF1A gene. One variant of uncertain significance was also found. Carriers of pathogenic variants had HLA-DRB1 risk alleles for autoimmune diabetes and clinical characteristics compatible with type 1 diabetes except for the absence of autoimmunity. Conclusion ZnT8A determination improves the diagnosis of autoimmune diabetes in pediatrics. At least 8% of pediatric patients suspected of type 1 diabetes and with undetectable autoimmunity have monogenic diabetes and can benefit from the correct diagnosis of the disease by genetic study., This work was partially supported by grants from Menarini Group Spain (BCA/16/030), University of the Basque Country, UPV/EHU (IT795-13), Department of Health of the Basque Government (GV2016111035) and ISCIII (PI14/01104) integrated into the National R&D&I Plan 2013-2016 and co-financed by FEDER (European Funds for Regional Development). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Objective: Molecular diagnosis is a useful diagnostic tool in calcium metabolism disorders. The calcium-sensing receptor (CaSR) is known to play a central role in the regulation of extracellular calcium homeostasis. We performed clinical, biochemical and genetic characterization of sequence anomalies in this receptor in a cohort of 130 individuals from 82 families with suspected alterations in the CASR gene, one of the largest series described. Methods: The CASR gene was screened for mutations by polymerase chain reaction followed by direct Sanger sequencing. Results: Presumed CaSR-inactivating mutations were found in 65 patients from 26 families. These patients had hypercalcemia (median: 11.3 mg/dL) but normal or abnormally high parathyroid hormone (PTH) levels (median: 52 pg/ mL). On the other hand, presumed CaSR-activating mutations were detected in 17 patients from eight families. These patients had a median serum calcium level of 7.4 mg/dL and hypoparathyroidism (median: PTH 13 pg/mL). Further, common polymorphisms previously associated with high blood ionized calcium levels were found in 27 patients (median calcium: 10.6 mg/dL; median PTH: 65 pg/mL) with no other alterations in CASR. Overall, we found 30 different mutations, of which, 14 have not been previously reported (p.Ala26Ser, p.Cys60Arg, plys119lle, p.Leu123Met, p.Glu133Val, p.Gly222Glu, p.Phe351lle, p.Cys542Tyr, p.Cys546Gly, p.Cys677Tyr, p.lle816Val, p.Ala887Asp, p.Glu934*, p.Pro935_Gln945dup). Conclusions: Patients with CASR mutations may not fit the classic clinical pictures of hypercalcemia with hypocalciuria or hypocalcemia with hypercalciuria. Molecular studies are important for confirming the diagnosis and distinguishing it from other entities. Our genetic analysis confirmed CaSR disorders in 82 patients in the study cohort.