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).

[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.

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.

Obstructive jaundice caused by a pancreaticoduodenal pseudoaneurysm.

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

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

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

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.

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.

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.