Radiological response to nivolumab in patients with hepatocellular carcinoma: A multicenter analysis of real-life practice

Background and aims: Immune-checkpoint inhibitors are effective in many advanced tumors. However, there is scarce information regarding the radiological response to these agents in hepatocellular carcinoma outside clinical trials. We aimed to describe the radiological response in a retrospective cohort of hepatocellular carcinoma patients treated with nivolumab and to analyze the radiological evolution according to tumor response at first post-treatment radiological assessment. Methods: We reviewed pre-treatment and post-treatment images (CT or MRI) obtained at different time-points in patients with hepatocellular carcinoma treated with nivolumab outside clinical trials at seven Spanish centers, assessing the response according to RECIST 1.1 and iRECIST and registering atypical responses. We also analyzed the imaging findings on subsequent assessments according to tumor status on the first posttreatment imaging assessment. Results: From the 118 patients with hepatocellular carcinoma treated with nivolumab, we finally analyzed data from 31 patients (71 % Child-Pugh A; 74 % BCLC-C). Median follow-up was 8.39 months [IQR 5.00-10.92]; median overall survival was 12.82 months (95 %CI 10.92-34.79). According to RECIST 1.1, the objective response rate was 16 % and according to iRECIST, the objective response rate was 22.6 %. Findings at the first post-treatment assessment varied, showing stable disease in 44.8 % of patients; findings during follow-up also varied widely, including 4 hyperprogressions and 3 pseudoprogressions. Conclusion: Imaging findings during nivolumab treatment are heterogeneous between and within patients. Progression of disease does not always signify treatment failure, and surrogate end-points may not reflect survival outcomes, making the management of hepatocellular carcinoma patients under immunotherapy challengin

COVID-19 Severity and Survival over Time in Patients with Hematologic Malignancies: A Population-Based Registry Study

Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified into early (February–June 2020; n = 769 (66%)) and later (July 2020–February 2021; n = 397 (34%)) cohorts. Propensity-score matched non-cancer patients were identified from the SEMI-COVID registry. A lower proportion of patients were hospitalized in the later waves (54.2%) compared to the earlier (88.6%), OR 0.15, 95%CI 0.11–0.20. The proportion of hospitalized patients admitted to the ICU was higher in the later cohort (103/215, 47.9%) compared with the early cohort (170/681, 25.0%, 2.77; 2.01–3.82). The reduced 30-day mortality between early and later cohorts of non-cancer inpatients (29.6% vs. 12.6%, OR 0.34; 0.22–0.53) was not paralleled in inpatients with hematologic malignancies (32.3% vs. 34.8%, OR 1.12; 0.81–1.5). Among evaluable patients, 27.3% had post COVID-19 condition. These findings will help inform evidence-based preventive and therapeutic strategies for patients with hematologic malignancies and COVID-19 diagnosis.Depto. de MedicinaFac. de MedicinaTRUEFundación Madrileña de Hematología y HemoterapiaFundación Leucemia y LinfomaAsociación Madrileña de Hematología y Hemoterapiapu

Fomento del espíritu emprendedor a través del análisis de las tendencias actuales del mercado informático basado en el uso de software libre y soluciones de automatización de servidores

Seleccionado en la convocatoria: Ayudas a la innovación e investigación educativa en centros docentes de niveles no universitarios, Gobierno de Aragón 2010-11El IES Santiago Hernández propone a sus alumnos del primer curso del ciclo formativo de grado superior de desarrollo de aplicaciones informáticas un proyecto de creación de una aplicación informática con un enfoque práctico. Sus objetivos son: fomentar en los alumnos el espíritu emprendedor; saber analizar las tendencias actuales en el mundo de la informática; habilitarse al trabajo en servidores remotos; familiarizarse con las ventajas del desarrollo de aplicaciones y gestión de datos desde la nube; habituarse al uso de entornos de producción; saber configurar distintos servicios de red; y establecer políticas de seguridad. Se realizan charlas orientativas, estudios de negocios y revisión de aplicaciones similares. Cada alumno aplica los conocimientos adquiridos al desarrollo de un programa de gestión de negocios aplicable a la vida real.Gobierno de Aragón. Departamento de Educación, Cultura y DeporteAragónDirección General de Política Educativa; Avda. Gómez Laguna, 25, planta 2; 50009 Zaragoza; Tel. +34976715416; Fax +34976715496ES

Unusual Clinical Manifestations in a Mexican Patient with Sanfilippo B Syndrome

We present an unusual Mexican patient affected with mucopolysaccharidosis type IIIB (MPS IIIB; also called Sanfilippo B syndrome, MIM #252920) bearing clinical features that have not previously been described for MPS IIIB (growth arrest, hypogonadotropic hypogonadism, and congenital heart disease). Chromosomal microarray analysis was useful in identifying runs of homozygosity at 17q11.1–q21.33 and supporting the diagnosis of an underlying autosomal recessive condition. Sanger sequencing of NAGLU (17q21.2, MIM*609701) allowed us to identify a pathogenic homozygous p.(Arg234Cys) genotype. This NAGLU allele could be related to that previously described in an Iberian MPS IIIB founder haplotype; results from the polymorphic marker D17S800 and rs2071046 led us to hypothesize that it may have been introduced to Mexico through the Spanish settlement. The analysis of a clinical exome sequencing ruled out other monogenic etiologies for the previously undescribed clinical MPS IIIB manifestations. Our findings contribute to further delineating the MPS IIIB phenotype and suggest possible phenotype–genotype correlations

HLA-DRB1

Background: Persistent infection with high-risk human papillomavirus (HPV) is a major risk factor for malignant lesions and cervical cancer. A widely studied element in the search for genetic factors influencing risk HPV infection diseases is allelic variation of the human leukocyte antigen (HLA) locus. The study was designed to search for HLA susceptibility alleles contributing to the persistence of HPV infection in Mexican women. Methods: A total of 172 subjects were divided into three groups: 1) HPV–persistent patients; 2) HPV–cleared; and 3) HPV–reinfected patients. They were screened for HPV types using a polymerase chain reaction (PCR). PCR-sequence specific oligonucleotide probes (PCR-SSOP) was used for HLA DRB1 and DQB1 typing. Results: We observed that HLA-DQB1*0501 allele might be associated with susceptibility of reinfection with HPV (p = 0.01, OR = 4.9, CI 95% = 1.3 -18.7). Allele frequency of HLA-DRB1*14 was particularly reduced in patients with cancer when compared with the HPV–persistent group (p = 0.04), suggesting that this allele is a possible protective factor for the development of cervical cancer (OR = 2.98). HLA-DRB1*07 might be associated with viral clearance (p = 0.04). Conclusions: Genetic markers for HPV infection susceptibility are different in each population, in Mexicans several HLA-DQB1 alleles might be associated with an enhanced risk for viral persistence. In contrast, DRB1*14, seems to confer protection against cervical cancer

Dominantly inherited Alzheimer's disease in Latin America: Genetic heterogeneity and clinical phenotypes

Introduction: A growing number of dominantly inherited Alzheimer's disease (DIAD) cases have become known in Latin American (LatAm) in recent years. However, questions regarding mutation distribution and frequency by country remain open. Methods: A literature review was completed aimed to provide estimates for DIAD pathogenic variants in the LatAm population. The search strategies were established using a combination of standardized terms for DIAD and LatAm. Results: Twenty-four DIAD pathogenic variants have been reported in LatAm countries. Our combined dataset included 3583 individuals at risk; countries with highest DIAD frequencies were Colombia (n = 1905), Puerto Rico (n = 672), and Mexico (n = 463), usually attributable to founder effects. We found relatively few reports with extensive documentation on biomarker profiles and disease progression. Discussion: Future DIAD studies will be required in LatAm, albeit with a more systematic approach to include fluid biomarker and imaging studies. Regional efforts are under way to extend the DIAD observational studies and clinical trials to Latin America.Fil: Llibre Guerra, Jorge J.. Washington University in St. Louis; Estados UnidosFil: Li, Yan. Washington University in St. Louis; Estados UnidosFil: Allegri, Ricardo Francisco. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chrem Mendez, Patricio Alexis. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Surace, Ezequiel Ignacio. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Llibre Rodriguez, Juan J.. Universidad de La Habana; CubaFil: Sosa, Ana Luisa. Instituto Nacional de Neurología y Neurocirugía; MéxicoFil: Aláez Verson, Carmen. Instituto Nacional de Medicina Genómica; MéxicoFil: Longoria, Erika Mariana. Instituto Nacional de Neurología y Neurocirugía; MéxicoFil: Tellez, Alberto. Instituto Nacional de Neurología y Neurocirugía; MéxicoFil: Carrillo Sánchez, Karol. Instituto Nacional de Medicina Genómica; MéxicoFil: Flores Lagunes, Luis Leonardo. Instituto Nacional de Medicina Genómica; MéxicoFil: Sánchez, Victor. Universidade de Sao Paulo; BrasilFil: Takada, Leonel Tadao. General Hospital of Fortaleza; BrasilFil: Nitrini, Ricardo. General Hospital of Fortaleza; BrasilFil: Ferreira Frota, Norberto Anizio. Grupo de Neurociencias de Antioquia; ColombiaFil: Benevides Lima, Joyce. Grupo de Neurociencias de Antioquia; ColombiaFil: Lopera, Francisco. Universidad de Puerto Rico; Puerto RicoFil: Ramírez, Laura. Universidad de Puerto Rico; Puerto RicoFil: Jiménez Velázquez, Ivonne. Universidad Nacional Pedro Henríquez Ureña; República DominicanaFil: Schenk, Christian. Universidad Nacional Pedro Henríquez Ureña; República DominicanaFil: Acosta, Daisy. Universidad de Chile.; Chile. Universidad del Desarrollo. Facultad de Medicina Clínica Alemana; ChileFil: Behrens, María Isabel. Washington University in St. Louis; Estados UnidosFil: Doering, Michelle. Washington University in St. Louis; Estados UnidosFil: Ziegemeier, Ellen. Washington University in St. Louis; Estados UnidosFil: Morris, John C.. Washington University in St. Louis; Estados UnidosFil: McDade, Eric. Washington University in St. Louis; Estados UnidosFil: Bateman, Randall J.. Washington University in St. Louis; Estados Unido