Implantation of a double allogeneic human engineered tissue graft on damaged heart: insights from the PERISCOPE phase I clinical trial.

BACKGROUND: In preclinical studies, the use of double allogeneic grafts has shown promising results in promoting tissue revascularization, reducing infarct size, preventing adverse remodelling and fibrosis, and ultimately enhancing cardiac function. Building upon these findings, the safety of PeriCord, an engineered tissue graft consisting of a decellularised pericardial matrix and umbilical cord Wharton's jelly mesenchymal stromal cells, was evaluated in the PERISCOPE Phase I clinical trial (NCT03798353), marking its first application in human subjects. METHODS: This was a double-blind, single-centre trial that enrolled patients with non-acute myocardial infarction eligible for surgical revascularization. Seven patients were implanted with PeriCord while five served as controls. FINDINGS: Patients who received PeriCord showed no adverse effects during post-operative phase and one-year follow-up. No significant changes in secondary outcomes, such as quality of life or cardiac function, were found in patients who received PeriCord. However, PeriCord did modulate the kinetics of circulating monocytes involved in post-infarction myocardial repair towards non-classical inflammation-resolving macrophages, as well as levels of monocyte chemoattractants and the prognostic marker Meteorin-like in plasma following treatment. INTERPRETATION: In summary, the PeriCord graft has exhibited a safe profile and notable immunomodulatory properties. Nevertheless, further research is required to fully unlock its potential as a platform for managing inflammatory-related pathologies. FUNDING: This work was supported in part by grants from MICINN (SAF2017-84324-C2-1-R); Instituto de Salud Carlos III (ICI19/00039 and Red RICORS-TERAV RD21/0017/0022, and CIBER Cardiovascular CB16/11/00403) as a part of the Plan Nacional de I + D + I, and co-funded by ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER) and AGAUR (2021-SGR-01437).

Hemicolectomy versus appendectomy for patients with appendiceal neuroendocrine tumours 1-2 cm in size: a retrospective, Europe-wide, pooled cohort study.

BACKGROUND: Awareness of the potential global overtreatment of patients with appendiceal neuroendocrine tumours (NETs) of 1-2 cm in size by performing oncological resections is increasing, but the rarity of this tumour has impeded clear recommendations to date. We aimed to assess the malignant potential of appendiceal NETs of 1-2 cm in size in patients with or without right-sided hemicolectomy. METHODS: In this retrospective cohort study, we pooled data from 40 hospitals in 15 European countries for patients of any age and Eastern Cooperative Oncology Group performance status with a histopathologically confirmed appendiceal NET of 1-2 cm in size who had a complete resection of the primary tumour between Jan 1, 2000, and Dec 31, 2010. Patients either had an appendectomy only or an appendectomy with oncological right-sided hemicolectomy or ileocecal resection. Predefined primary outcomes were the frequency of distant metastases and tumour-related mortality. Secondary outcomes included the frequency of regional lymph node metastases, the association between regional lymph node metastases and histopathological risk factors, and overall survival with or without right-sided hemicolectomy. Cox proportional hazards regression was used to estimate the relative all-cause mortality hazard associated with right-sided hemicolectomy compared with appendectomy alone. This study is registered with ClinicalTrials.gov, NCT03852693. FINDINGS: 282 patients with suspected appendiceal tumours were identified, of whom 278 with an appendiceal NET of 1-2 cm in size were included. 163 (59%) had an appendectomy and 115 (41%) had a right-sided hemicolectomy, 110 (40%) were men, 168 (60%) were women, and mean age at initial surgery was 36·0 years (SD 18·2). Median follow-up was 13·0 years (IQR 11·0-15·6). After centralised histopathological review, appendiceal NETs were classified as a possible or probable primary tumour in two (1%) of 278 patients with distant peritoneal metastases and in two (1%) 278 patients with distant metastases in the liver. All metastases were diagnosed synchronously with no tumour-related deaths during follow-up. Regional lymph node metastases were found in 22 (20%) of 112 patients with right-sided hemicolectomy with available data. On the basis of histopathological risk factors, we estimated that 12·8% (95% CI 6·5 -21·1) of patients undergoing appendectomy probably had residual regional lymph node metastases. Overall survival was similar between patients with appendectomy and right-sided hemicolectomy (adjusted hazard ratio 0·88 [95% CI 0·36-2·17]; p=0·71). INTERPRETATION: This study provides evidence that right-sided hemicolectomy is not indicated after complete resection of an appendiceal NET of 1-2 cm in size by appendectomy, that regional lymph node metastases of appendiceal NETs are clinically irrelevant, and that an additional postoperative exclusion of metastases and histopathological evaluation of risk factors is not supported by the presented results. These findings should inform consensus best practice guidelines for this patient cohort. FUNDING: Swiss Cancer Research foundation.

Validation of an indirect in-house ELISA using synthetic peptides to detect antibodies anti-gp90 and gp45 of the equine infectious anaemia virus.

BACKGROUND: Equine infectious anaemia (EIA) is controlled by the identification of seropositive animals. The official diagnostic method is the agar gel immunodiffusion (AGID) test, which detects antibodies against a viral core protein (p26). Although AGID is inexpensive and specific, the report of results takes considerable time and the test has low analytical sensitivity. OBJECTIVE: To validate our in-house indirect ELISAgp90/45 , following the World Organization of Animal Health (OIE) criteria. STUDY DESIGN: Test validation. METHODS: Synthetic peptides gp90 and gp45 were used as antigens in ELISAgp90/45 . Tests used for validation, calibration and linear working operating range, analytical and diagnostic sensitivity and specificity, repeatability and reproducibility were assessed by comparing them with the AGID test and using 1844 equine sera grouped into five different panels. RESULTS: We were able to replace the National References Sera with our Internal Reference Sera. ELISAgp90/45 had acceptable repeatability and reproducibility. Analytical sensitivity of the ELISAgp90/45 was 800 times greater than that of AGID test for positive sera and 400 times greater for weak positive sera. ELISAgp90/45 also showed optimal analytical specificity, since no cross-reactivity was detected with antibodies against other equine viruses. One sample was positive by AGID test and negative by ELISAgp90/45. ELISAgp90/45 was performed using 243 EIA positive and 878 negative equid sera, and showed a diagnostic sensitivity of 99.59% [CI 97.73%-99.99%] and a diagnostic specificity of 90.32% [CI 88.17%-92.19%], compared to AGID test; thus, it was demonstrated to be a robust test. MAIN LIMITATIONS: Samples were derived from naturally infected equid populations showing heterogeneous clinical states: therefore, their status was uncertain and some horses were sampled more than once. The AGID test may not be the most useful gold standard. CONCLUSION: ELISAgp90/45 is a useful tool for the diagnosis of EIAV infection and meets validation requirements established by the OIE.

Long-term outcomes with the On-X bileaflet mitral valve: clinical events up to 17 years in 661 patients.

OBJECTIVES: This study reports long-term clinical outcomes-up to 17 years-among patients undergoing mitral valve replacement with the On-X bileaflet mechanical valve. Prior data regarding long-term outcomes with the On-X mitral valve have been limited. METHODS: This retrospective observational study included all patients who underwent mitral valve replacement with the On-X (Standard or Conform-X) valve at 2 major Spanish cardiac surgery centres between 2001 and 2018. The primary study end point was freedom from death. The secondary study end points included surgical mortality and freedom from any valve-related events. Data were obtained from an institutional database, medical records review, direct telephone interviews or the Spanish population registry. Statistical and Kaplan-Meier analyses were performed. RESULTS: A total of 661 patients (mean age 63.1 ± 10.9 years, 63% female) were followed for a mean of 5.6 years (range, 0-17.4 years). Survival at 5, 10 and 15 years was 85%, 71% and 63%, respectively. Surgical mortality was 7.3% (48/661). The linearized rate of global mortality was 1.3% patient-year. Freedom from reoperation was 97%, 95% and 92% at 5, 10 and 15 years, respectively; freedom from anticoagulation-related events was 94%, 89% and 89%, respectively. Multivariable analysis showed that mortality increased with total length of stay, age, smoking history, severe pulmonary hypertension and a permanent pacemaker. Patients who received the On-X 25 -mm valve had decreased long-term survival relative to patients who received other On-X valve sizes, possibly due to underlying risk factors. CONCLUSIONS: Patients in this study showed good long-term survival and freedom from valve-related events.

Characterization of ADAT2/3 molecules in Trypanosoma cruzi and regulation of mucin gene expression by tRNA editing.

Adenosine-to-inosine conversion at position 34 (A34-to-I) of certain tRNAs is essential for expanding their decoding capacity. This reaction is catalyzed by the adenosine deaminase acting on tRNA (ADAT) complex, which in Eukarya is formed by two subunits: ADAT2 and ADAT3. We herein identified and thoroughly characterized the ADAT molecules from the protozoan pathogen Trypanosoma cruzi, the causative agent of Chagas Disease. TcADAT2 and TcADAT3 spontaneously form a catalytically active complex, as shown by expression in engineered bacteria and/or by the increased ex vivo tRNA A-to-I deamination activity of T. cruzi epimastigotes overexpressing TcADAT subunits. Importantly, enhanced TcADAT2/3 activity in transgenic parasites caused a shift in their in vivo tRNAThrAGU signature, which correlated with significant changes in the expression of the Thr-rich TcSMUG proteins. To our knowledge, this is the first evidence indicating that T. cruzi tRNA editing can be modulated in vivo, in turn post-transcriptionally changing the expression of specific genes. Our findings suggest tRNA editing/availability as a forcible step in controlling gene expression and driving codon adaptation in T. cruzi. Moreover, we unveil certain differences between parasite and mammalian host tRNA editing and processing, such as cytosine-to-uridine conversion at position 32 of tRNAThrAGU in T. cruzi, that may be exploited for the identification of novel druggable targets of intervention.

Variability in Oral Iron Prescription and the Effect on Spanish Mothers' Health: A Prospective Longitudinal Study.

BACKGROUND: No consensus exists regarding the hemoglobin (Hb) values that define postpartum anemia. Knowledge is currently lacking regarding prescription and consumption practices, which prevents evaluating the rational use of iron supplementation postpartum. AIM: In this study, our objective was to describe this practice and analyze its association with maternal health outcomes. METHODS: A prospective observational study was conducted with 1010 women aged between 18 and 50. The hemoglobin value on the first postpartum day; the prescription schedule at hospital discharge; iron consumption; and data on hemoglobin, serum ferritin, maternal fatigue, type of breastfeeding, and perceived health six weeks after delivery were collected. FINDINGS: Oral iron was prescribed to 98.1% of mothers with anemia and 75.8% without anemia. At the same Hb value, the maximum amount of total iron prescribed was between 8 and 10 times greater than the minimum amount. Iron intake was significantly lower than prescribed (p < 0.01). At six weeks, anemic mothers who took iron presented a 3.6-, 3-, and 2.4-times lower probability of iron deficiency, anemia, and abandoning breastfeeding, respectively. DISCUSSION: Postpartum iron intake shows a protective effect on iron deficiency and anemia at six weeks, but not on fatigue or self-perceived health level. CONCLUSION: We conclude that there is wide variability in the prescription regimen. Oral iron supplementation can benefit mothers with anemia and harm those without. Subsequent studies should further explore the Hb figure that better discriminates the need for postpartum iron.

Internet das Coisas e blockchain no Sistema Único de Saúde: a proteção dos dados sensíveis diante da Lei Geral de Proteção de Dados / Internet of Things and blockchain used in the Brazilian Unified Health System: how to protect sensitive data considering the imminence of the Data Protection Law / Internet de las cosas y cadena de bloques utilizado en el Sistema Único de Salud brasileño: cómo proteger los datos confidenciales ante la Ley General de Protección de Datos

Objetivo: O Sistema Único de Saúde (SUS) vem investido nas tecnologias da internet das coisas ­ Internet of Things (IoT), em inglês ­ para coletar dados dos pacientes. Esse artigo aponta as fragilidades quanto à privacidade de usuários do SUS e propor uma solução teórica, ainda a ser testada a partir de uma infraestrutura pautada em armazenamento pessoal de dados ­ personal data stores (PDS), em inglês ­ ou, a partir da segurança da blockchain. Metodologia: realizou-se revisão narrativa da literatura nacional e internacional relacionados a instrumentos, políticas e casos voltados a tecnologias de informação e comunicação na saúde a fim de apontar as fragilidades quanto à privacidade de usuários desse sistema. Resultados: percebeu-se que ainda existe uma falta de transparência no tratamento dos dados pessoais e pouco accountability por parte dos cidadãos, se fazendo necessária uma mudança de estratégia tecnológica e de governança. Conclusão: o PDS, de fato, empodera o usuário na medida que dá maior controle e transparência sobre o tratamento de seus dados. No entanto, essa solução, em um sistema como o utilizado pelo Departamento de Informática do SUS, pode comprometer a precisão dos dados usados nas políticas públicas, ao mesmo tempo que pode comprometer alguns direitos dos cidadãos, pois são dados salvos em registros e os metadados estão disponíveis publicamente. A implementação do PDS ainda não possui perspectiva de resultado ótimo. Ainda existem algumas restrições metodológicas quanto aos direitos dos cidadãos ou à eficiência do Estado, mas é um passo no empoderamento civil e uma melhoria exigida por lei quanto à privacidade e à proteção de dados pessoais.

Objective: Brazilian Unified Health System (SUS, in Portuguese) has invested in Internet of Things (IoT) technologies to collect data from patients. This article aims to point out the weaknesses regarding the privacy of users of the SUS and to propose a theoretical solution, yet to be evaluated, and based on a Personal Data Storages (PDS) infrastructure or on blockchain security. Methods: aA narrative review of national and international literature related to instruments, policies, and cases related to information and communication technologies in health was conducted to point out the weaknesses regarding the privacy of users of this system. Results: there is still a lack of transparency in the treatment of personal data and little accountability on the part of citizens, making it necessary to change the technological and governance strategy. Conclusion: PDS empowers users as it gives greater control and transparency over the treatment of data. However, this solution, in a system like the one used by their Computer Department, can compromise the accuracy of the data used in public policies, while it can compromise some citizens' rights, as this data is saved in records and the metadata is publicly available. The implementation of a solution like this does not yet have the prospect of an optimal result, without any methodological restriction on citizens' rights or the efficiency of the State, but it is a step in civil empowerment and an improvement required by law concerning privacy and protection of personal data. The implementation of the PDS does not yet have the prospect of an optimal result. There are still methodological restrictions regarding the rights of citizens or the efficiency of the State. But it is a step in civil empowerment and an improvement required by law in terms of privacy and the protection of personal data.

Objetivo: el Sistema Único de Salud de Brasil (SUS) ha invertido en tecnologías de Internet de las cosas (IoT) para recopilar datos de los pacientes. Este artículo tiene como objetivo señalar las debilidades con respecto a la privacidad de los usuarios del SUS y proponer una solución teórica, aún por probar basada en una infraestructura basada en Personal Data Storages (PDS) o almacenamiento personal de datos, basado en la seguridad de blockchain. Metodología: se realizó una revisión narrativa de la literatura nacional e internacional relacionada con instrumentos, políticas y casos relacionados con las tecnologías de la información y la comunicación en salud con el fin de señalar las debilidades en cuanto a la privacidad de los usuarios de este sistema. Resultados: se notó, entonces, que aún existe falta de transparencia en el tratamiento de estos datos personales y poca rendición de cuentas por parte de la ciudadanía, por lo que es necesario cambiar la estrategia tecnológica y de gobernanza. Conclusión: se concluye que PDS, de hecho, empodera a los usuarios ya que brinda un mayor control y transparencia sobre el tratamiento de sus datos. Sin embargo, esta solución, en un sistema como el utilizado por el Departamento de Computación del SUS, puede comprometer la precisión de los datos utilizados en las políticas públicas, al mismo tiempo que puede comprometer algunos derechos civiles, ya que estos datos se guardan en registros y metadatos están disponibles públicamente. La implementación de una solución como esta todavía no tiene la perspectiva de un resultado óptimo, sin ninguna restricción metodológica sobre los derechos de los ciudadanos o la eficiencia del Estado, pero es un paso en el empoderamiento civil y una mejora requerida por la ley con respecto a la privacidad y protección de datos personales. La implementación del PDS aún no tiene la perspectiva de un resultado óptimo. Aún existen algunas restricciones metodológicas en cuanto a los derechos de los ciudadanos o la eficiencia del Estado. Pero es un paso en el empoderamiento civil y una mejora requerida por la ley en términos de privacidad y protección de datos personales.

Perfil epidemiológico de los casos notificados de covid-19 residentes del área programática del Hospital Parmenio Piñero Período del 5 de marzo al 20 de agosto de 2020 / Epidemiological profile of the notified cases of covid-19 in residents of the programmatic area of the Parmenio Piñero Hospital Period from March 5 to August 20 of 2020

Introducción. La pandemia de covid-19 afecta al país. El objetivo de este estudio fue describir características clínicas y epidemiológicas de las personas con covid-19 residentes del área programática del Hospital P. Piñero. Metodología. Estudio descriptivo y transversal. Se analizaron los denominados "Caso sospechoso de covid-19, influenza y otros virus respiratorios" del SNVS 2.0. Se calculó la estadística descriptiva y la tasa de incidencia acumulada y letalidad. Resultados. Se notificaron hasta el 20 de agosto 33.847 casos sospechosos, de los cuales 14.418 fueron confirmados (42,6%). La tasa de incidencia acumulada fue 4674,6 por 100.000 habitantes. Hubo aumento de casos confirmados hasta la semana epidemiológica 26, luego se verifica el amesetamiento y la irregular distribución. La distribución de la edad fue similar en ambos sexos, la mediana fue de 33 años (RIC: 22-48). Los síntomas más frecuentes fueron respiratorios y neurológicos. Fallecieron 248 personas de covid-19. La tasa de letalidad fue 1,7%. Las comorbilidades más frecuentes fueron hipertensión arterial y diabetes, con una media de 70,7 años (DE 15,0). Aumentó la letalidad a mayor edad, y la Villa 1-11-14 tuvo una mayor letalidad. Conclusión. Hubo mayor riesgo de morbilidad y mortalidad por covid-19 en el área programática, mostrando una situación más crítica en la Villa 1-11-14, lo que refleja una desigualdad en el riesgo de enfermar y de morir dentro del área programática del Hospital P. Piñero

Introduction. The covid-19 pandemic affects the country. The objective of this study was to describe the clinical and epidemiological characteristics of people with covid-19 who live in the programmatic area of the Piñero Hospital. Methodology. Descriptive and cross-sectional study. SNVS 2.0 "Suspected cases of covid-19, influenza and other respiratory viruses" were analyzed. Descriptive statistics and cumulative incidence rate and fatality were calculated. Results. 33,847 suspected cases were reported up to august 20, 14,418 were confirmed (42.6%). The cumulative incidence rate was 4674.6 per 100,000 populations. There was an increase in the number of confirmed cases until the 26th epidemiologic week 26, when we observed a plateau. The age distribution was similar in both sexes; the median was 33 years (IQR: 22-48). The most frequent symptoms were respiratory and neurological. 248 people died of covid-19. The fatality rate was 1.7%. The most frequent comorbidities were arterial hypertension and diabetes, with a mean of 70.7 years (SD 15.0). The lethality increased at an older age, presenting in the Villa 1-11-14 higher lethality. Conclusion. There was a higher risk of morbility and mortality from covid-19 in the programmatic area, showing a more critical situation in Villa 1-11-14, reflecting an inequality about illness and death, in the Piñero hospital programmatic area

Removal of Phenolic Compounds from Water Using Copper Ferrite Nanosphere Composites as Fenton Catalysts.

Copper ferrites containing Cu+ ions can be highly active heterogeneous Fenton catalysts due to synergic effects between Fe and Cu ions. Therefore, a method of copper ferrite nanosphere (CFNS) synthesis was selected that also permits the formation of cuprite, obtaining a CFNS composite that was subsequently calcined up to 400 °C. Composites were tested as Fenton catalysts in the mineralization of phenol (PHE), p-nitrophenol (PNP) and p-aminophenol (PAP). Catalysts were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and magnetic measurements. Degradation of all phenols was practically complete at 95% total organic carbon (TOC) removal. Catalytic activity increased in the order PHE < PNP < PAP and decreased when the calcination temperature was raised; this order depended on the electronic effects of the substituents of phenols. The as-prepared CFNS showed the highest catalytic activity due to the presence of cubic copper ferrite and cuprite. The Cu+ surface concentration decreased after calcination at 200 °C, diminishing the catalytic activity. Cuprite alone showed a lower activity than the CFNS composite and the homogeneous Fenton reaction had almost no influence on its overall activity. CFNS activity decreased with its reutilization due to the disappearance of the cuprite phase. Degradation pathways are proposed for the phenols.

Synthesis and characterization of α-d-Galp-(1 → 3)-ß-d-Galp epitope-containing neoglycoconjugates for chagas disease serodiagnosis.

The immunodominant epitope α-d-Galp-(1 → 3)-ß-d-Galp-(1 → 4)-d-GlcNAc, expressed in the mucins of the infective trypomastigote stage of Trypanosoma cruzi has been proposed for multiple clinical applications, from serodiagnosis of protozoan caused diseases to xenotransplantation or cancer vaccinology. It was previously shown that the analogue trisaccharide, with glucose in the reducing end instead of GlcNAc, was as efficient as the natural trisaccharide for recognition of chagasic antibodies. Here we describe the synthesis of α-d-Galp-(1 → 3)-ß-d-Galp-(1 → 4)-d-Glcp functionalized as the 6-aminohexyl glycoside and its conjugation to BSA using the squarate method. The conjugate of 6-aminohexyl α-d-Galp-(1 → 3)-ß-d-Galp was also prepared. Both neoglycoconjugates were recognized by serum samples of Trypanosoma cruzi-infected individuals and thus, are promising tools for the improvement of Chagas disease diagnostic applications.

Molecular and antigenic characterization of Trypanosoma cruzi TolT proteins.

BACKGROUND: TolT was originally described as a Trypanosoma cruzi molecule that accumulated on the trypomastigote flagellum bearing similarity to bacterial TolA colicins receptors. Preliminary biochemical studies indicated that TolT resolved in SDS-PAGE as ~3-5 different bands with sizes between 34 and 45 kDa, and that this heterogeneity could be ascribed to differences in polypeptide glycosylation. However, the recurrent identification of TolT-deduced peptides, and variations thereof, in trypomastigote proteomic surveys suggested an intrinsic TolT complexity, and prompted us to undertake a thorough reassessment of this antigen. METHODS/PRINCIPLE FINDINGS: Genome mining exercises showed that TolT constitutes a larger-than-expected family of genes, with at least 12 polymorphic members in the T. cruzi CL Brener reference strain and homologs in different trypanosomes. According to structural features, TolT deduced proteins could be split into three robust groups, termed TolT-A, TolT-B, and TolT-C, all of them showing marginal sequence similarity to bacterial TolA proteins and canonical signatures of surface localization/membrane association, most of which were herein experimentally validated. Further biochemical and microscopy-based characterizations indicated that this grouping may have a functional correlate, as TolT-A, TolT-B and TolT-C molecules showed differences in their expression profile, sub-cellular distribution, post-translational modification(s) and antigenic structure. We finally used a recently developed fluorescence magnetic beads immunoassay to validate a recombinant protein spanning the central and mature region of a TolT-B deduced molecule for Chagas disease serodiagnosis. CONCLUSION/SIGNIFICANCE: This study unveiled an unexpected genetic and biochemical complexity within the TolT family, which could be exploited for the development of novel T. cruzi biomarkers with diagnostic/therapeutic applications.

Relación entre actividades de tiempo libre y cognición en adultos mayores: una revisión de estudios argentinos e iberoamericanos / Relationship between leisure activities and cognition in elderly adults: a review of argentine and Iberoamerican studies

El envejecimiento poblacional implica un desafío para la salud pública por las patologías cuyos casos aumentan con la extensión de la vida. Se ha propuesto que ciertas actividades de la vida diaria (AVDs) avanzadas de tiempo libre poseen un efecto bené+co en la cognición de los adultos mayores. El objetivo de este trabajo fue relevar estudios empíricos presentando evidencia respecto a la relación entre dichas actividades y el funcionamiento cognitivo, para países iberoamericanos. Se incluyeron trabajos escritos en español, portugués e inglés, de enero de 2012 a mayo de 2017, involucrando a adultos de 60 y más años de edad no institucionalizados. Se hallaron 15 trabajos. Considerados en su conjunto, existiría evidencia de una relación entre las mencionadas actividades y el rendimiento cognitivo. Los trabajos de diseño prospectivo y los de intervención indicarían que la realización de dichas actividades avanzadas incide bene+ciosamente en el funcionamiento cognitivo.

Population aging implies a challenge to public health for the pathologies whose cases increase with the extension of life. It has been proposed that certain leisure advanced activities of daily living (ATLs) have a bene+cial effect on the cognition of the elderly. The objective of this work was to relieve empirical studies presenting evidence regarding the relationship between these activities and cognitive functioning, for Iberoamerican countries. Works written in Spanish, Portuguese and English were included from January 2012 to May 2017, involving non-institutionalized adults aged 60 and over. Fifteen papers were found. Considered as a whole, there would be evidence of a relationship between these activities and cognitive performance. Prospective design and interventional studies would indicate that such advanced activities has a bene+cial impact on cognitive functioning.

Intermediate Care Unit After Cardiac Surgery: Impact on Length of Stay and Outcomes.

INTRODUCTION AND OBJECTIVES: Current postoperative management of adult cardiac surgery often comprises transfer from the intensive care unit (ICU) to a conventional ward. Intermediate care units (IMCU) permit hospital resource optimization. We analyzed the impact of an IMCU on length of stay (both ICU and in-hospital) and outcomes (in-hospital mortality and 30-day readmissions) after adult cardiac surgery (IMCU-CS). METHODS: From November 2012 to April 2015, 1324 consecutive patients were admitted to a university hospital for cardiac surgery. In May 2014, an IMCU-CS was established for postoperative care. For the purposes of this study, patients were classified into 2 groups, depending on the admission period: pre-IMCU-CS (November 2012-April 2014, n=674) and post-IMCU-CS (May 2014-April 2015, n=650). RESULTS: There were no statistically significant differences in age, sex, risk factors, comorbidities, EuroSCORE 2, left ventricular ejection fraction, or the types of surgery (valvular in 53%, coronary in 26%, valvular plus coronary in 11.5%, and aorta in 1.8%). The ICU length of stay decreased from 4.9±11 to 2.9±6 days (mean±standard deviation; P<.001); 2 [1-4] to 1 [0-3] (median [Q1-Q3]); in-hospital length of stay decreased from 13.5±15 to 12.7±11 days (mean±standard deviation; P=.01); 9 [7-13] to 9 [7-11] (median [Q1-Q3]), in pre-IMCU-CS to post-IMCU-CS, respectively. There were no statistically significant differences in in-hospital mortality (4.9% vs 3.5%; P=.28) or 30-day readmission rate (4.3% vs 4.2%; P=.89). CONCLUSIONS: After the establishment of an IMCU-CS for postoperative cardiac surgery, there was a reduction in ICU and in-hospital mean lengths of stay with no increase in in-hospital mortality or 30-day readmissions.

Extranodal marginal zone B cell lymphoma: An unexpected complication in children with Sjögren's syndrome.

Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by the infiltration of lymphocytes into exocrine glands, resulting in the typical sicca symptoms. Unlike adults, primary SS is a very rare condition in childhood, and the risk of malignancy in juvenile SS (JSS) has not been defined. We report the detection of extranodal marginal zone B-cell lymphoma (EMZL) occurring in two children with SS. Fine needle aspiration of the salivary glands (SG) showed nonspecific findings that led to delayed diagnosis of SS. The diagnosis of B-cell lymphoma associated with JSS was based on morphologic and immunohistochemical staining done during the biopsy. To highlight awareness of EMZL as a timely and appropriate update of an unusual complication in children with SS.

Rationale and design of a multicentre, prospective, randomised, controlled clinical trial to evaluate the efficacy of the adipose graft transposition procedure in patients with a myocardial scar: the AGTP II trial.

INTRODUCTION: Cardiac adipose tissue is a source of progenitor cells with regenerative capacity. Studies in rodents demonstrated that the intramyocardial delivery of cells derived from this tissue improves cardiac function after myocardial infarction (MI). We developed a new reparative approach for damaged myocardium that integrates the regenerative properties of cardiac adipose tissue with tissue engineering. In the adipose graft transposition procedure (AGTP), we dissect a vascularised flap of autologous pericardial adipose tissue and position it over the myocardial scarred area. Following encouraging results in acute and chronic MI porcine models, we performed the clinical trial (NCT01473433, AdiFLAP trial) to evaluate safety in patients with chronic MI undergoing coronary artery bypass graft. The good safety profile and trends in efficacy warranted a larger trial. STUDY DESIGN: The AGTP II trial (NCT02798276) is an investigator initiated, prospective, randomised, controlled, multicentre study to assess the efficacy of the AGTP in 108 patients with non-revascularisable MI. Patients will be assigned to standard clinical practice or the AGTP. The primary endpoint is change in necrotic mass ratio by gadolinium enhancement at 91 and 365 days. Secondary endpoints include improvement in regional contractibility by MRI at 91 and 365 days; changes in functional MRI parameters (left ventricular ejection fraction, left and right ventricular geometric remodelling) at 91 and 365 days; levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) at 7, 91 and 365 days; appearance of arrhythmias from 24 hour Holter monitoring at 24 hours, and at 91 and 365 days; all cause death or re-hospitalisation at 365 days; and cardiovascular death or re-hospitalisation at 365 days. ETHICS AND DISSEMINATION: The institutional review board approved the trial which will comply with the Declaration of Helsinki. All patients will provide informed consent. It may offer a novel, effective and technically simple technique for patients with no other therapeutic options. The results will be submitted to indexed medical journals and national and international meetings. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT02798276, pre-results.

Evaluation of bond strength of a conventional adhesive system in irradiated teeth / Avaliação da resistência de união de um sistema adesivo convencional em dentes irradiados

Introduction: One of the most common treatments of head and neck cancer patients is radiotherapy, a treatment method which uses ionizing radiation beam and destroys tumor cells, minimizing damage to neighbor cells. Purpose: To evaluate the bond strength of a conventional adhesive system in irradiated teeth. Method: 24 third human molars, 12 of which were randomly exposed to radiation and prepared from the removal of occlusal enamel, then exposed to a flat dentine surface. The adhesive system Stae was applied according to the manufacturer's instructions. Next, two 2 mm increments of resin were implemented. The samples were hemi sectioned specimens, originating shapped toothpick. To evaluate the bond strength, a micro tensile test was done with 500N load and speed of 0.5 mm/minute. Result: There was no statistically significant difference between the bond strength of teeth which were or were not exposed to radiation and which used a conventional adhesive system. Conclusion: Although the radiation doses applied may cause some alterations in microscopic range in dental tissues, it can be concluded that these alterations do not influence in the bond strength in dentin of irradiated teeth.

Introdução: Um dos tratamentos mais comuns dos pacientes portadores de câncer na região de cabeça e pescoço é a radioterapia, um método de tratamento que utiliza feixe de radiação ionizante e tem por finalidade destruir as células tumorais, minimizando danos às células vizinhas. Objetivo: Avaliar a resistência de união de um sistema adesivo convencional em dentes irradiados. Método: 24 terceiros molares, dos quais 12 foram aleatoriamente expostos à irradiação e preparados a partir da remoção do esmalte oclusal, expondo, dessa forma, uma superfície de dentina. O sistema adesivo Stae foi aplicado de acordo com as instruções do fabricante e em seguida acrescentou-se dois incrementos de resina de 2 mm. Os corpos de prova foram hemi-seccionados originando espécimes em forma de palito. Para avaliação da resistência de união, foi realizado o ensaio de microtração com carga de 500N e velocidade de 0,5mm/min. Resultado: Não houve diferença estatística significante entre a resistência de união de dentes que foram ou não expostos à irradiação e que utilizaram um sistema adesivo convencional. Conclusão: Embora as doses de radiação aplicadas causem algum tipo de alteração em escala microscópica nos tecidos dentários, essas alterações não interferiram na resistência de união.

Incidence and predictors of new-onset atrioventricular block requiring pacemaker implantation after sutureless aortic valve replacement.

OBJECTIVES: In high-risk patients with severe aortic stenosis, aortic valve replacement (AVR) with a sutureless Perceval prosthesis (SU-AVR) can be performed instead of conventional AVR or transcatheter aortic valve implantation. Little data are available regarding postoperative conduction disorders after SU-AVR. We aimed to determine the incidence and predictors of new-onset complete atrioventricular block (NO-AVB) requiring permanent cardiac stimulation following SU-AVR. METHODS: We studied consecutive patients who underwent SU-AVR between 2013 and 2015. Early patients underwent partial aortic decalcification and subannular valve implantation (standard technique), while later patients underwent complete/symmetrical decalcification and intra-annular valve deployment (modified technique). Predictive baseline and procedural variables and electrocardiographic parameters were identified using a logistic regression model. RESULTS: We included 140 patients (mean age, 78 ± 6.5 years; mean Log EuroSCORE II, 8.9 ± 10%; 28.6% concomitant myocardial revascularization). The most common postoperative conduction disturbances were LBBB (25%), NO-AVB (12.1%) and first-degree atrioventricular block (AVB) (7.9%). The incidence of NO-AVB was 61% lower with the modified versus the standard technique (P= 0.04). NO-AVB predominantly appeared within 24 h post-surgery, occurring >24 h post-surgery in only 2 patients (both with baseline conduction defects). Independent predictors of NO-AVB included baseline left QRS axis deviation (LaQD; P= 0.03), first-degree AVB (P< 0.01) and standard surgical technique (P= 0.02). CONCLUSIONS: NO-AVB is a frequent complication following SU-AVR, and its incidence strongly depends on the surgical technique. Baseline first-degree AVB and LaQD independently predict NO-AVB and should be considered when deciding the duration of postoperative electrocardiographic monitoring.

First-in-man Safety and Efficacy of the Adipose Graft Transposition Procedure (AGTP) in Patients With a Myocardial Scar.

BACKGROUND: The present study evaluates the safety and efficacy of the Adipose Graft Transposition Procedure (AGTP) as a biological regenerative innovation for patients with a chronic myocardial scar. METHODS: This prospective, randomized single-center controlled study included 10 patients with established chronic transmural myocardial scars. Candidates for myocardial revascularization were randomly allocated into two treatment groups. In the control arm (n=5), the revascularizable area was treated with CABG and the non-revascularizable area was left untouched. Patients in the AGTP-treated arm (n=5) were treated with CABG and the non-revascularizable area was covered by a biological adipose graft. The primary endpoint was the appearance of adverse effects derived from the procedure including hospital admissions and death, and 24-hour Holter monitoring arrhythmias at baseline, 1week, and 3 and 12months. Secondary endpoints of efficacy were assessed by cardiac MRI. FINDINGS: No differences in safety were observed between groups in terms of clinical or arrhythmic events. On follow-up MRI testing, participants in the AGTP-treated arm showed a borderline smaller left ventricular end systolic volume (LVESV; p=0.09) and necrosis ratio (p=0.06) at 3months but not at 12months. The AGTP-treated patient with the largest necrotic area and most dilated chambers experienced a noted improvement in necrotic mass size (-10.8%), and ventricular volumes (LVEDV: -55.2mL and LVESV: -37.8mL at one year follow-up) after inferior AGTP. INTERPRETATION: Our results indicate that AGTP is safe and may be efficacious in selected patients. Further studies are needed to assess its clinical value. (ClinicalTrials.org NCT01473433, AdiFlap Trial).

Epirubicin Plus Cyclophosphamide Followed by Docetaxel Versus Epirubicin Plus Docetaxel Followed by Capecitabine As Adjuvant Therapy for Node-Positive Early Breast Cancer: Results From the GEICAM/2003-10 Study.

PURPOSE: Capecitabine is an active drug in metastatic breast cancer (BC). GEICAM/2003-10 is an adjuvant trial to investigate the integration of capecitabine into a regimen of epirubicin and docetaxel for node-positive early BC. PATIENTS AND METHODS: Patients with operable node-positive BC (T1-3/N1-3) were eligible. After surgery, 1,384 patients were randomly assigned to receive epirubicin plus cyclophosphamide (EC; 90 and 600 mg/m(2), respectively, × four cycles), followed by docetaxel (100 mg/m(2) × four cycles; EC-T) or epirubicin plus docetaxel (ET; 90 and 75 mg/m(2), respectively, × four cycles), followed by capecitabine (1,250 mg/m(2) twice a day on days 1 to 14, × four cycles; ET-X); all regimens were given every 3 weeks. The primary end point was invasive disease-free survival. Secondary end points included safety (with an alopecia-specific study) and overall survival (OS). RESULTS: After a median follow-up of 6.6 years and 297 events, 86% of patients who received EC-T and 82% of those who received ET-X were invasive disease free at 5 years (hazard ratio, 1.30; 95% CI, 1.03 to 1.64; log-rank P = .03). The OS difference between arms was not statistically significant (hazard ratio, 1.13; 95% CI, 0.82 to 1.55; log-rank P = .46). The most frequent grade 3 to 4 adverse events in the EC-T versus ET-X arms were neutropenia (19% v 10%), with 7% febrile neutropenia across arms; fatigue (13% v 11%); diarrhea (3% v 11%); hand-foot syndrome (2% v 20%); mucositis (6% v 5%); vomiting (both, 5%); and myalgia (4.5% v 1%). Incomplete scalp hair recovery was more frequent in the EC-T than ET-X arm (30% v 14%), and patients who received EC-T wore wigs significantly longer than those who received ET-X (8.35 v 6.03 months). CONCLUSION: Invasive disease-free survival, but not OS, was significantly superior for patients with node-positive early BC who received the adjuvant standard schedule EC-T than for those who received the experimental ET-X regimen. Toxicity profiles differed substantially across arms.