Subcuticular suture and incisional surgical-site infection in elective hepatobiliary and pancreatic surgery: an open-label, pragmatic randomized clinical trial (CLOSKIN trial).

BACKGROUND: Subcuticular suture has proven to reduce superficial incisional SSI (si-SSI) in clean surgery. However, question remains regarding clean-contaminated procedures. The aim of this study is to assess if subcuticular suture is superior to staples in reducing si-SSI incidence in elective HBP surgery. METHODS: Single-centre, open-label, parallel, pragmatic randomized clinical trial conducted at a referral tertiary Hospital between January 2020 and April 2022. Patients eligible for elective HBP surgery were randomly assigned (1:1) to subcuticular suture or surgical staples wound closure using a minimisation method based on previously confirmed risk factors. The primary endpoint was the incidence of si-SSI. Considered secondary endpoints were major postoperative morbidity in both groups, additional wound complications, median hospital length of stay and need for re-hospitalisation. RESULTS: Of the 379 patients, 346 patients were randomly assigned to receive skin closure with staples (n = 173) or subcuticular suture (n = 173). After further exclusion of 11 participants, 167 and 168 patients, respectively in the control and the experimental group received their allocated intervention. For the primary endpoint, no significant differences in si-SSI rate were found: 17 (9.82%) staples group vs. 8 (4.62%) in subcuticular suture group (p = 0.062). Subset analysis confirmed absence of significant differences. As for secondary endpoints, overall wound complications did not differ significantly between two procedures: 19 (10.98%) vs. 10 (6.35%) (p = 0.127). There were no treatment related adverse events. However, occurrence of si-SSI contributed to major postoperative morbidity in both groups (p < 0.001 and p = 0.018) and to a substantially prolonged postoperative hospitalization (p = 0.015). CONCLUSIONS: Subcuticular suture might offer a relative benefit for skin closure reducing incidence of si-SSI after elective HBP surgery, although this was found not to be clinically relevant. Yet, this should not be interpreted as equivalence among both treatments. Therefore, wound closure strategy should not be based only on these grounds. TRIAL REGISTRATION NUMBER: ISRCTN Registry number ISRCTN37315612 (registration date: 14/01/2020).

Barreras y facilitadores del programa de ejercicio EfiKroniK para pacientes con enfermedad crónica en atención primaria / Barriers and facilitators of the EfiKroniK exercise program for people with chronic diseases in Primary Care

Objetivo: Explorar las percepciones de los pacientes durante el programa de ejercicio y detectar las barreras y los facilitadores que influyen en la adherencia al ejercicio al término de la supervisión. Diseño: Estudio observacional cualitativo con grupos de discusión como principal técnica de recogida de datos. Lugar: Centros de atención primaria de Vizcaya. Participantes: De los 175 pacientes aleatorizados del ensayo híbrido de efectividad-implementación se incluyeron 19 pacientes del grupo intervención (12 pacientes oncohematológicos en estadios avanzados y 7 con trastorno mental grave). Métodos: Se ha realizado un análisis de contenido de las transcripciones generadas, combinando un enfoque deductivo, basado en los dominios del marco teórico PRACTIS y uno inductivo, basado en los postulados de la teoría fundamentada. Resultados: Los participantes se mostraron satisfechos con el programa EfiKroniK y los beneficios fueron: descubrimiento de los beneficios del ejercicio físico, la gestión psicológica y emocional de la enfermedad, los beneficios de la comunicación entre iguales y del apoyo emocional y romper con la rutina de la enfermedad. Los participantes disminuyeron los niveles de ejercicio físico al término de la supervisión por la confluencia de diferentes barreras. Conclusión:Un programa de ejercicio supervisado realizado en atención primaria contribuyó a mejorar la calidad de vida, el bienestar emocional y social de pacientes en estadios avanzados de su enfermedad. Nuestro estudio ha identificado barreras potenciales y facilitadores asociados con la participación en el ejercicio y su continuidad; sin embargo, es necesario promover la coordinación intersectorial en el espacio sociosanitario para fomentar una atención integrada y continuada a los pacientes crónicos.(AU)

Objective: Explore patients’ perceptions during a supervised exercise program and detect the barriers and facilitators that influence exercise adherence after the supervision period. Design: A qualitative observational study with three focus groups as the main data collection technique was conducted. Site: Primary Health centers of Bizkaia. Participants: Out of the 175 randomized patients in the hybrid effectiveness-implementation trial, a sample of 19 patients from the intervention group were included in the qualitative study (12 advanced-stage onco-haematological patients and seven with severe mental disorders). Methods: Content analysis of the generated transcripts was performed by combining a deductive approach, based on the domains of the PRACTIS theoretical framework, and an inductive one, based on the postulates of the Grounded Theory. Results: The data analysis showed that participants were satisfied with the EfiKroniK program and that the main identified benefits were discovery of the benefits of physical exercise, the psychological and emotional management of the disease, the benefits from peer communication and emotional support, and the break from routine of their illness. Participants decreased the levels of physical exercise at the end of the supervision6 due to the confluence of several barriers. Conclusion: A supervised exercise program carried out in Primary Care contributed to the improvement of the quality of life as well as the emotional and social well-being of patients with advanced-stage diseases. Our study identified potential barriers and facilitators associated with exercise participation and its continuity, however, it is necessary to encourage inter-sectoral coordination within the socio-health system to promote integrated and continuous care for chronic patients.(AU)

Toxoplasma gondii infection and peripheral-blood gene expression profiling of older people reveals dysregulation of cytokines and identifies hub genes as potential therapeutic targets.

Infections of humans with the protozoan parasite Toxoplasma gondii (T. gondii) can lead to the disease's development, even in an asymptomatic status. However, the mechanisms that result in these clinical outcomes after infection are poorly understood. This study aimed to explore the molecular pathogenesis of toxoplasmosis-related inflammation through next-generation sequencing, to assess RNA expression profiles in peripheral blood from 5 female patients with chronic toxoplasmosis and 5 healthy female controls. All plasma samples were analyzed for anti-Toxoplasma IgG and IgM antibody titers by using electrochemiluminescence. Detection of acute and chronic toxoplasmosis was carried out using the ELISA IgG avidity. We evaluated the levels of INF-γ, IL-2, IL-12, TNF-α, IL-10, and IL-1ß in culture supernatants of Peripheral Blood Mononuclear Cells infected with Toxoplasma lysate antigen (TLA) prepared with tachyzoites of strain T. gondii RH. Differential expression analysis was performed using DESeq2, pathway and enrichment analysis of DEGs was done on WEB-based Gene SeT AnaLysis Toolkit (WebGestalt) and Protein-protein interaction was carried out using NetworkAnalyst with STRING. In older people with chronic asymptomatic infection, a significant difference in the levels of inflammatory cytokines INF-γ and IL-2 was observed compared to seronegative individuals. Our results revealed differences in the regulation of critical biological processes involved in host responses to chronic T. gondii infection. Gene ontology analysis revealed several biologically relevant inflammatory and immune-related pathways.

[Barriers and facilitators of the EfiKroniK exercise program for people with chronic diseases in Primary Care]. / Barreras y facilitadores del programa de ejercicio EfiKroniK para pacientes con enfermedad crónica en atención primaria.

OBJECTIVE: Explore patients' perceptions during a supervised exercise program and detect the barriers and facilitators that influence exercise adherence after the supervision period. DESIGN: A qualitative observational study with three focus groups as the main data collection technique was conducted. SITE: Primary Health centers of Bizkaia. PARTICIPANTS: Out of the 175 randomized patients in the hybrid effectiveness-implementation trial, a sample of 19 patients from the intervention group were included in the qualitative study (12 advanced-stage onco-haematological patients and seven with severe mental disorders). METHODS: Content analysis of the generated transcripts was performed by combining a deductive approach, based on the domains of the PRACTIS theoretical framework, and an inductive one, based on the postulates of the Grounded Theory. RESULTS: The data analysis showed that participants were satisfied with the EfiKroniK program and that the main identified benefits were discovery of the benefits of physical exercise, the psychological and emotional management of the disease, the benefits from peer communication and emotional support, and the break from routine of their illness. Participants decreased the levels of physical exercise at the end of the supervision6 due to the confluence of several barriers. CONCLUSION: A supervised exercise program carried out in Primary Care contributed to the improvement of the quality of life as well as the emotional and social well-being of patients with advanced-stage diseases. Our study identified potential barriers and facilitators associated with exercise participation and its continuity, however, it is necessary to encourage inter-sectoral coordination within the socio-health system to promote integrated and continuous care for chronic patients.

Molecular and cellular evolution of the primate dorsolateral prefrontal cortex.

The granular dorsolateral prefrontal cortex (dlPFC) is an evolutionary specialization of primates that is centrally involved in cognition. We assessed more than 600,000 single-nucleus transcriptomes from adult human, chimpanzee, macaque, and marmoset dlPFC. Although most cell subtypes defined transcriptomically are conserved, we detected several that exist only in a subset of species as well as substantial species-specific molecular differences across homologous neuronal, glial, and non-neural subtypes. The latter are exemplified by human-specific switching between expression of the neuropeptide somatostatin and tyrosine hydroxylase, the rate-limiting enzyme in dopamine production in certain interneurons. The above molecular differences are also illustrated by expression of the neuropsychiatric risk gene FOXP2, which is human-specific in microglia and primate-specific in layer 4 granular neurons. We generated a comprehensive survey of the dlPFC cellular repertoire and its shared and divergent features in anthropoid primates.

Mechanisms of Binding Specificity among bHLH Transcription Factors.

The transcriptome of every cell is orchestrated by the complex network of interaction between transcription factors (TFs) and their binding sites on DNA. Disruption of this network can result in many forms of organism malfunction but also can be the substrate of positive natural selection. However, understanding the specific determinants of each of these individual TF-DNA interactions is a challenging task as it requires integrating the multiple possible mechanisms by which a given TF ends up interacting with a specific genomic region. These mechanisms include DNA motif preferences, which can be determined by nucleotide sequence but also by DNA's shape; post-translational modifications of the TF, such as phosphorylation; and dimerization partners and co-factors, which can mediate multiple forms of direct or indirect cooperative binding. Binding can also be affected by epigenetic modifications of putative target regions, including DNA methylation and nucleosome occupancy. In this review, we describe how all these mechanisms have a role and crosstalk in one specific family of TFs, the basic helix-loop-helix (bHLH), with a very conserved DNA binding domain and a similar DNA preferred motif, the E-box. Here, we compile and discuss a rich catalog of strategies used by bHLH to acquire TF-specific genome-wide landscapes of binding sites.

Prophylactic HIPEC in pT4 Colon Tumors: Proactive Approach or Overtreatment?

BACKGROUND: The peritoneum is the second most common site for metastasis in patients with colorectal cancer. Various factors have been studied to identify patients at risk of developing peritoneal carcinomatosis (PC), including T4 tumors. The objectives were to assess the incidence of synchronous and metachronous PC, explore potential risk factors for developing PC as the only site of metastasis, and identify which patients might be candidates for prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: We conducted a retrospective analysis of 125 patients with pT4 colon cancer who underwent surgery in a single center between January 2010 and December 2014. RESULTS: Of the 947 colon cancer patients who underwent surgery, 125 (13.2%) were diagnosed with pT4a or b colon carcinoma. The median follow-up was 3.7 years. The overall rate of PC was 34.3%, being synchronous in 12% and metachronous in 22.3% of cases. The 8% and 6% of synchronous and metachronous cases of PC respectively were isolated (single site) metastasis. The incidence of PC was 6.1% at 1 year and 14.5% at 3 years after surgery. pT4 was not found to be an independent risk factor for the development of PC (p = 0.231). Nonetheless, the rate of metachronous PC as a single site of metastasis was higher in patients with pT4 tumors and peritoneal nodules around the primary tumor and/or tumor perforation (p = 0.027) and/or who underwent emergency surgery (p = 0.043) than other patients. CONCLUSIONS: Considering pT4 tumor stage as the only risk factor for the development of PC in deciding whether to administer prophylactic HIPEC would lead to unjustified overtreatment.

Malrotación intestinal en adultos: causa infrecuentede obstrucción intestinal / Intestinal malrotation in adults: An uncommon cause of intestinal obstruction

La malrotación intestinal es una malformación congénita que afecta hasta al 1 % de la población. Aproximada-mente, el 90 % de los casos se presenta en la edad pediátrica y, rara vez, en la población adulta, lo que convierte a esta alteración en un reto para los profesionales sanitarios. Se presenta el caso de una paciente que se inició con un cuadro de obstrucción intestinal y abdomen agudo; se le diagnosticó malrotación intestinal, vólvulo y obstrucción por bridas, durante la laparotomía exploradora ur-gente. El conocimiento de condición patológica es imprescindible para poder brindarle un correcto tratamiento quirúrgico

The intestinal malrotation is a congenital malformation that affects up to 1% of the population. Approximately 90% of cases are diagnosed in the pediatric age and rarely in the adult population, which makes this pathology a challenge for health professionals.This is a case of a patient who presented with intestinal obstruction and acute abdomen that was diagnosed during the emergency exploratory laparotomy with intestinal malrotation, volvulus and obstruction. The knowledge of this pathology is essential to perform its correct surgical treatment

A rare presentation of gallstones: Bouveret´s syndrome, a case report.

CT images and endoscopic findings in a case of Bouveret's syndrome.

Síndrome de Bouveret / A rare presentation of gallstones: Bouveret´s syndrome, a case report

No disponible

Obstructive jaundice caused by a pancreaticoduodenal pseudoaneurysm.

Obstructive jaundice caused by a pancreaticoduodenal pseudoaneurysm, probably related to a chronic pancreatitis.

Ictericia obstructiva por pseudoaneurisma de arteria pancreaticoduodenal / Obstructive jaundice caused by a pancreaticoduodenal pseudoaneurysm

No disponible

Oestrogen receptor polymorphisms are an associated risk factor for mild cognitive impairment and Alzheimer disease in women APOE {varepsilon}4 carriers: a case-control study.

OBJECTIVES: Examine the role of single nucleotide polymorphisms (SNPs) in the oestrogen receptor (ER) genes: rs9340799, rs2234693, rs2228480 (in the ESR1 gene) and rs4986938 (in the ESR2 gene) as a risk factor for amnesic mild cognitive impairment (MCIa) and Alzheimer's disease (AD) and its possible association with the apolipoprotein E (APOE) gene. DESIGN: We have investigated the independent and combined association of different alleles of the oestrogen receptor genes and APOE*ε4 allele with cognitive impairment using a case-control design. SETTING: Participants were prospectively recruited from the neurology departments of several Basque Country hospitals. PARTICIPANTS: This study comprised 816 Caucasian participants who were aged 50 years and older: 204 MCIa, 350 sporadic patients with AD and 262 healthy controls. PRIMARY AND SECONDARY OUTCOME MEASURES: Clinical criteria and neuropsychological tests were used to establish the diagnostic groups (MCIa, AD and healthy controls). A dichotomous variable was used for each allele and genotype and the association with MCIa and AD was established using Logistic Regression Models. RESULTS: Neither alleles nor genotypes of SNPs rs9340799, rs2234693, rs2228480 and rs4986938 of oestrogen receptor genes (ESR1 and ESR2) are independently associated with the risk of MCIa or AD. However, the genetic profile created with the combination of the less represented alleles of these SNPs (expressed as XPAA) was associated with an increased risk for MCIa (OR=3.30, 95% CI 1.28 to 8.54, p=0.014) and AD (OR=5.16, 95% CI 2.19 to 12.14, p<0.001) in women APOE*ε4 allele carriers. CONCLUSIONS: The less represented alleles of SNPs studied are associated with MCIa and AD in APOE*E4 carriers. In particular, the genetic profile created with the less represented alleles of ESR1 and ESR2 SNPs are associated with an increased risk for MCIa and AD in women APOEε4 allele carriers.

[Role of genetics in the etiology of synucleinopathies]. / Papel de la genética en la etiología de las sinucleinopatías.

The protein family known as synucleins is composed of α-, ß- and γ-synuclein. The most widely studied is the α-synuclein protein due to its participation in essential processes of the central nervous system. Neurotoxicity of this protein is related to the presence of multiplications (duplications and triplications) and point mutations in the gene sequence of the α-synuclein gene (SNCA), differential expression of its isoforms and variations in post-transductional modifications. Neurotoxicity is also related to cytoplasmic inclusions known as Lewy bodies (LBs) and Lewy neurites (LNs), which are also present in α-synucleinopathies. In general, the ß-synuclein protein, codified by the SNCB gene, acts as a regulator of processes triggered by α-synuclein and its function is altered by variations in the gene sequence, while γ-synuclein, codified by the SNCG gene, seems to play a major role in certain tumoral processes.

Papel de la genética en la etiología de las sinucleinopatías / Role of genetics in the etiology of synucleinopathies

La familia de las proteínas conocidas como sinucleínas está compuesta por la α, la β y la γ-sinucleína. La proteína α-sinucleína es la más estudiada por su participación en procesos esenciales del sistema nervioso central. La neurotoxicidad de esta proteína está relacionada con la presencia de multiplicaciones (duplicaciones y triplicaciones) y mutaciones puntuales en la secuencia génica del gen de la α-sinucleína (SNCA), expresión diferencial de sus isoformas, así como variaciones en las modificaciones postransduccionales. Está relacionada con las inclusiones citoplasmáticas conocidas como cuerpos de Lewy y las neuritas de Lewy presentes también en las denominadas α-sinucleinopatías. En general, la proteína β-sinucleína codificada por el gen SNCB interviene como regulador de los procesos desencadenados por la α-sinucleína, viéndose alterada su función por variaciones en la secuencia génica, mientras que γ-sinucleína, codificada por el gen SNCG, parece jugar un papel transcendental en determinados procesos tumorales (AU)

The protein family known as synucleins is composed of α-, β- and γ-synuclein. The most widely studied is the α-synuclein protein due to its participation in essential processes of the central nervous system. Neurotoxicity of this protein is related to the presence of multiplications (duplications and triplications) and point mutations in the gene sequence of the α-synuclein gene (SNCA), differential expression of its isoforms and variations in post-transductional modifications. Neurotoxicity is also related to cytoplasmic inclusions known as Lewy bodies (LBs) and Lewy neurites (LNs), which are also present in α-synucleinopathies. In general, the β-synuclein protein, codified by the SNCB gene, acts as a regulator of processes triggered by α-synuclein and its function is altered by variations in the gene sequence, while γ-synuclein, codified by the SNCG gene, seems to play a major role in certain tumoral processes (AU)

Perfiles genéticos de longevidad y envejecimiento saludable en nonagenarios del País Vasco / Genetic profiles of longevity and healthy cognitive aging in nonagenarians from the Basque Country

Introducción. En la actualidad existen notables diferencias en el envejecimiento de los individuos de las poblaciones modernas. Mientras que algunos de ellos disfrutan de un prolongado envejecimiento saludable, otros desarrollan enfermedades neurodegenerativas como la enfermedad de Alzheimer (EA). Los factores ambientales son decisivos en este hecho, pero la genética puede contribuir a explicar las diferencias observadas. Recientemente se ha postulado que los genes de la longevidad podrían ser también neuroprotectores. Objetivos. Evaluar si determinadas variantes genéticas relacionadas con la longevidad pueden tener un carácter neuroprotector. Métodos. Los sujetos a estudio son las personas con una edad superior a 90 años. De cada participante se realizará la recogida de datos sociodemográficos, clínicos y múltiples valoraciones: cognitiva, funcional, antropométrica, nutricional, sensorial y física. Además, se realizará el análisis de 64 loci SNPs, distribuidos en 13 genes candidatos FOXO3, SIRT1, TOMM40, APOE, PICALM, COMT, CETP, CLU, CR1, IL-6, PCK-1, ZNF224 y ACE mediante Taqman array. Resultados. Obtener un mayor conocimiento sobre los alelos infra/sobre representados en las personas nonagenarias. Además, la comparación de las características genéticas de los nonagenarios con EA con aquellos libres de enfermedad permitirá observar vinculaciones entre determinados alelos con la protección o el riesgo de EA. La información asociada de los participantes permitirá crear subgrupos mostrando las interacciones entre el ambiente y las variaciones genéticas en relación al envejecimiento saludable y la EA. Conclusión. El estudio de la variabilidad genética de las personas nonagenarias nos puede dar información sobre los alelos relacionados con la longevidad y la neuroprotección(AU)

Introduction. Currently there are notable differences in the aging of individuals in modern populations. While some of them enjoy a long healthy aging, others develop neurodegenerative diseases, such as Alzheimer's disease (AD). Environmental factors are critical, but genetics could explain the differences observed. It has recently been postulated that longevity genes might also be neuroprotective. Objectives. To assess whether certain genetic variants associated with longevity might have a neuroprotective effect. Methods. The subjects of this study are people older than 90 years. We will collect sociodemographic and clinical data and multiple assessments, cognitive, functional, anthropometric, nutritional, sensory and physical each participant. In addition, 64 SNPs loci distributed in 13 candidate genes FOXO3, SIRT1, TOMM40, APOE, PICALM, COMT, CETP, CLU, CR1, IL-6, PCK-1, ZNF224 and ACE will be analysed by Taqman array. Results. It is hoped to gain more knowledge about under/over-represented alleles in nonagenarians. Furthermore, comparison of the genetic characteristics of nonagenarians with AD with those free of disease will enable links to be seen between certain alleles with protection or the risk of AD. Associated information on the participants will create subgroups showing the interactions between environment and genetic variation in relation to healthy aging and AD. Conclusion. The study of the genetic variability of nonagenarians can give us information on the alleles associated with longevity and neuroprotection(AU)

[Genetic profiles of longevity and healthy cognitive aging in nonagenarians from the Basque Country]. / Perfiles genéticos de longevidad y envejecimiento saludable en nonagenarios del País Vasco.

INTRODUCTION: Currently there are notable differences in the aging of individuals in modern populations. While some of them enjoy a long healthy aging, others develop neurodegenerative diseases, such as Alzheimer's disease (AD). Environmental factors are critical, but genetics could explain the differences observed. It has recently been postulated that longevity genes might also be neuroprotective. OBJECTIVES: To assess whether certain genetic variants associated with longevity might have a neuroprotective effect. METHODS: The subjects of this study are people older than 90 years. We will collect sociodemographic and clinical data and multiple assessments, cognitive, functional, anthropometric, nutritional, sensory and physical each participant. In addition, 64 SNPs loci distributed in 13 candidate genes FOXO3, SIRT1, TOMM40, APOE, PICALM, COMT, CETP, CLU, CR1, IL-6, PCK-1, ZNF224 and ACE will be analysed by Taqman array. RESULTS: It is hoped to gain more knowledge about under/over-represented alleles in nonagenarians. Furthermore, comparison of the genetic characteristics of nonagenarians with AD with those free of disease will enable links to be seen between certain alleles with protection or the risk of AD. Associated information on the participants will create subgroups showing the interactions between environment and genetic variation in relation to healthy aging and AD. CONCLUSION: The study of the genetic variability of nonagenarians can give us information on the alleles associated with longevity and neuroprotection.

The COMT Val158 Met polymorphism as an associated risk factor for Alzheimer disease and mild cognitive impairment in APOE 4 carriers.

BACKGROUND: The aim of this study is to examine the influence of the catechol-O-methyltranferase (COMT) gene (polymorphism Val158 Met) as a risk factor for Alzheimer's disease (AD) and mild cognitive impairment of amnesic type (MCI), and its synergistic effect with the apolipoprotein E gene (APOE).A total of 223 MCI patients, 345 AD and 253 healthy controls were analyzed. Clinical criteria and neuropsychological tests were used to establish diagnostic groups.The DNA Bank of the University of the Basque Country (UPV-EHU) (Spain) determined COMT Val158 Met and APOE genotypes using real time polymerase chain reaction (rtPCR) and polymerase chain reaction (PCR), and restriction fragment length polymorphism (RFLPs), respectively. Multinomial logistic regression models were used to determine the risk of AD and MCI. RESULTS: Neither COMT alleles nor genotypes were independent risk factors for AD or MCI. The high activity genotypes (GG and AG) showed a synergistic effect with APOE epsilon4 allele, increasing the risk of AD (OR = 5.96, 95%CI 2.74-12.94, p < 0.001 and OR = 6.71, 95%CI 3.36-13.41, p < 0.001 respectively). In AD patients this effect was greater in women.In MCI patients such as synergistic effect was only found between AG and APOE epsilon4 allele (OR = 3.21 95%CI 1.56-6.63, p = 0.02) and was greater in men (OR = 5.88 95%CI 1.69-20.42, p < 0.01). CONCLUSION: COMT (Val158 Met) polymorphism is not an independent risk factor for AD or MCI, but shows a synergistic effect with APOE epsilon4 allele that proves greater in women with AD.