Effect of colchicine on perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery (COP-AF): an international randomised trial.

BACKGROUND: Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications. METHODS: COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing major non-cardiac thoracic surgery were randomly assigned (1:1) to receive oral colchicine 0·5 mg twice daily or matching placebo, starting within 4 h before surgery and continuing for 10 days. Randomisation was done with use of a computerised, web-based system, and was stratified by centre. Health-care providers, patients, data collectors, and adjudicators were masked to treatment assignment. The coprimary outcomes were clinically important perioperative atrial fibrillation and MINS during 14 days of follow-up. The main safety outcomes were a composite of sepsis or infection, and non-infectious diarrhoea. The intention-to-treat principle was used for all analyses. This trial is registered with ClinicalTrials.gov, NCT03310125. FINDINGS: Between Feb 14, 2018, and June 27, 2023, we enrolled 3209 patients (mean age 68 years [SD 7], 1656 [51·6%] male). Clinically important atrial fibrillation occurred in 103 (6·4%) of 1608 patients assigned to colchicine, and 120 (7·5%) of 1601 patients assigned to placebo (hazard ratio [HR] 0·85, 95% CI 0·65 to 1·10; absolute risk reduction [ARR] 1·1%, 95% CI -0·7 to 2·8; p=0·22). MINS occurred in 295 (18·3%) patients assigned to colchicine and 325 (20·3%) patients assigned to placebo (HR 0·89, 0·76 to 1·05; ARR 2·0%, -0·8 to 4·7; p=0·16). The composite outcome of sepsis or infection occurred in 103 (6·4%) patients in the colchicine group and 83 (5·2%) patients in the placebo group (HR 1·24, 0·93-1·66). Non-infectious diarrhoea was more common in the colchicine group (134 [8·3%] events) than the placebo group (38 [2·4%]; HR 3·64, 2·54-5·22). INTERPRETATION: In patients undergoing major non-cardiac thoracic surgery, administration of colchicine did not significantly reduce the incidence of clinically important atrial fibrillation or MINS but increased the risk of mostly benign non-infectious diarrhoea. FUNDING: Canadian Institutes of Health Research, Accelerating Clinical Trials Consortium, Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario, Population Health Research Institute, Hamilton Health Sciences, Division of Cardiology at McMaster University, Canada; Hanela Foundation, Switzerland; and General Research Fund, Research Grants Council, Hong Kong.

[Association of illicit drug use in pregnant women and congenital syphilis in a public hospital in Mexico]. / Asociación del consumo de drogas ilícitas en mujeres embarazadas y sífilis congénita en un Hospital Público de México.

We conducted a nested case-control study within a cohort with the aim of studying the association between illicit drug use and congenital syphilis (CS). Cases were diagnosed based on treponemal and non-treponemal tests conducted both in the mother and the newborn (NB). Multivariate analysis with logistic regression was performed. A total of 6171 births with a mean gestational age of 37.8 weeks were recorded and 62 CS events were diagnosed (incidence 10.5 events/1000 NB). Associated maternal factors were illicit drug use (OR 14.08, 95% CI 1.19-166.6), <5 prenatal visits (OR 2.9, 95% CI 1.12-7.53), more than two sexual partners (OR 3.76, 95% CI 1.62-8.71) and professional education level (OR 0.06, 95% CI 0.005-0.85). Among the mothers of the cases presented, the prevalence of illicit drug use was 22.6% and the most frequent drugs were methamphetamines and cannabis.

Mendelian Susceptibility to Mycobacterial Disease: Retrospective Clinical and Genetic Study in Mexico.

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare genetic disorder characterized by impaired immunity against intracellular pathogens, such as mycobacteria, attenuated Mycobacterium bovis-Bacillus Calmette-Guérin (BCG) vaccine strains, and environmental mycobacteria in otherwise healthy individuals. Retrospective study reviewed the clinical, immunological, and genetic characteristics of patients with MSMD in Mexico. Overall, 22 patients diagnosed with MSMD from 2006 to 2021 were enrolled: 14 males (64%) and eight females. After BCG vaccination, 12 patients (70%) developed BCG infection. Furthermore, 6 (22%) patients developed bacterial infections mainly caused by Salmonella, as what is described next in the text is fungal infections, particularly Histoplasma. Seven patients died of disseminated BCG disease. Thirteen different pathogenic variants were identified in IL12RB1 (n = 13), IFNGR1 (n = 3), and IFNGR2 (n = 1) genes. Interleukin-12Rß1 deficiency is the leading cause of MSMD in our cohort. Morbidity and mortality were primarily due to BCG infection.

Rationale and design of the colchicine for the prevention of perioperative atrial fibrillation in patients undergoing major noncardiac thoracic surgery (COP-AF) trial.

BACKGROUND: Perioperative atrial fibrillation (AF) and myocardial injury after noncardiac surgery (MINS) are common complications after noncardiac surgery. Inflammation has been implicated in the pathogenesis of both disorders. The COP-AF trial tests the hypothesis that colchicine reduces the incidence of perioperative AF and MINS in patients undergoing major noncardiac thoracic surgery. METHODS AND RESULTS: The 'COlchicine for the Prevention of Perioperative Atrial Fibrillation' (COP-AF) trial is an international, blinded, randomized trial that compares colchicine to placebo in patients aged at least 55 years and undergoing major noncardiac thoracic surgery with general anesthesia. Exclusion criteria include a history of AF and a contraindication to colchicine (eg, severe renal dysfunction). Oral colchicine at a dose of 0.5 mg or matching placebo is given within 4 hours before surgery. Thereafter, patients receive colchicine 0.5 mg or placebo twice daily for a total of 10 days. The 2 independent co-primary outcomes are clinically important perioperative AF (including atrial flutter) and MINS during 14 days of follow-up. The main safety outcomes are sepsis or infection and non-infectious diarrhea. We aim to enroll 3,200 patients from approximately 40 sites across 11 countries to have at least 80% power for the independent evaluation of the 2 co-primary outcomes. The COP-AF main results are expected in 2023. CONCLUSIONS: COP-AF is a large randomized and blinded trial designed to determine whether colchicine reduces the risk of perioperative AF or MINS in patients who have major noncardiac thoracic surgery.

Congenital infection by cytomegalovirus in newborns with very low birth weight.

Not available.

Brain metastases from non-small cell lung carcinoma: an overview of classical and novel treatment strategies.

Background: The development of brain metastases is a common problem in patients diagnosed with non-small cell lung carcinoma (NSCLC). Technological advances in surgery and radiotherapy have allowed greater local control. Moreover, the emergence of targeted therapies and immunotherapy with greater activity on the central nervous system than classical chemotherapy have given way to new strategies in the treatment of brain metastases. We review the current role of local treatments, surgery and radiotherapy, and the most effective combination strategies with the new systemic treatments. Relevance for patients: Brain metastases frequently occur during the course of NSCLC. In recent years, a range of treatments have appeared, such as targeted treatments or immunotherapy, with greater activity at the brain level than classical chemotherapy. Radiotherapy treatment is also now much more conformal and ablative doses can be delivered to the volume of the metastatic area, providing greater local control and less neurological toxicity. However, surgery is still required in cases where anatomopathological specimens are needed and when compressive effects appear. An important challenge is how to combine these treatments to achieve the best control and minimise patients' neurological impairments, especially because of limited experience with the new target drugs, and the unknown toxicity of the different combinations. Future research should therefore focus on these areas in order to establish the best strategies for the treatment of brain metastases from non-small cell lung cancer. Core tips: In this work, we intend to elucidate the best therapeutic options for patients diagnosed with brain metastases of NSCL, which include: surgery, WBRT, radiosurgery or systemic treatment, and the most effective combinations and timings of them, and the ones with the lowest associated toxicity.

Expresión de infección por SARS-CoV-2 en niños: infección aguda sintomática y síndrome inflamatorio multisistémico.

No disponible.

Injection Partners, HCV, and HIV Status among Rural Persons Who Inject Drugs in Puerto Rico.

BACKGROUND: The prevalence of hepatitis C (HCV) and HIV among persons who inject drugs (PWID) and the ability of these diseases to spread through injection networks are well documented in urban areas. However, less is known about injection behaviors in rural areas. OBJECTIVES: This study focuses on the association between the number of self-reported injection partners with the PWID's self-reported HCV and HIV status. Injection networks provide paths for infection and information to flow, and are important to consider when developing prevention and intervention strategies. METHODS: Respondent driven sampling was used to conduct 315 interviews with PWID in rural Puerto Rico during 2015. Negative binomial regression was used to test for associations between the number of self-reported injection partners and self-reported HCV and HIV statuses. Multinomial logistic regression was used to test for associations with the participant's self-reported HCV and HIV statuses. RESULTS: Self-reported HCV status is significantly associated with injection risk network size. Injection partner networks of self-reported HCV- respondents are half what is reported by those with a positive or unknown status. Self-reported HIV statuses are not associated with different numbers of injection partners. CONCLUSIONS: Smaller injection networks among those who self-report a HCV- status suggests that those who believe their status to be negative may take protective action by reducing their injection network compared to those have a self-reported HCV+ or an unknown status. Although the cross-sectional design of the study makes it difficult verify, such behavior has implications for prevention programs attempting to prevent HCV transmission.

The North American Forest Database: going beyond national-level forest resource assessment statistics.

Forests cannot be managed sustainably without reliable data to inform decisions. National Forest Inventories (NFI) tend to report national statistics, with sub-national stratification based on domestic ecological classification systems. It is becoming increasingly important to be able to report statistics on ecosystems that span international borders, as global change and globalization expand stakeholders' spheres of concern. The state of a transnational ecosystem can only be properly assessed by examining the entire ecosystem. In global forest resource assessments, it may be useful to break national statistics down by ecosystem, especially for large countries. The Inventory and Monitoring Working Group (IMWG) of the North American Forest Commission (NAFC) has begun developing a harmonized North American Forest Database (NAFD) for managing forest inventory data, enabling consistent, continental-scale forest assessment supporting ecosystem-level reporting and relational queries. The first iteration of the database contains data describing 1.9 billion ha, including 677.5 million ha of forest. Data harmonization is made challenging by the existence of definitions and methodologies tailored to suit national circumstances, emerging from each country's professional forestry development. This paper reports the methods used to synchronize three national forest inventories, starting with a small suite of variables and attributes.

Using Network Sampling and Recruitment Data to Understand Social Structures Related to Community Health in a Population of People Who Inject Drugs in Rural Puerto Rico.

OBJECTIVE: This research examined the social network and recruitment patterns of a sample of people who inject drugs (PWIDs) in rural Puerto Rico, in an attempt to uncover systematic clustering and between-group social boundaries that potentially influence disease spread. METHODS: Respondent driven sampling was utilized to obtain a sample of PWID in rural Puerto Rico. Through eight initial "seeds", 317 injection drug users were recruited. Using recruitment patterns of this sample, estimates of homophily and affiliation were calculated using RDSAT. RESULTS: Analyses showed clustering within the social network of PWID in rural Puerto Rico. In particular, females showed a very high tendency to recruit male PWID, which suggests low social cohesion among female PWID. Results for (believed) HCV status at the time of interview indicate that HCV+ individuals were less likely to interact with HCV- individuals or those who were unaware of their status, and may be acting as "gatekeepers" to prevent disease spread. Individuals who participated in a substance use program were more likely to affiliate with one another. The use of speedballs was related to clustering within the network, in which individuals who injected this mixture were more likely to affiliate with other speedball users. CONCLUSION: Social clustering based on several characteristics and behaviors were found within the IDU population in rural Puerto Rico. RDS was effective in not only garnering a sample of PWID in rural Puerto Rico, but also in uncovering social clustering that can potentially influence disease spread among this population.

Noncovalent Bonding Controls Selectivity in Heterogeneous Catalysis: Coupling Reactions on Gold.

Enhancing the selectivity of catalytic processes has potential for substantially increasing the sustainability of chemical production. Herein, we establish relationships between reaction selectivity and molecular structure for a homologous series of key intermediates for oxidative coupling of alcohols on gold using a combination of experiment and theory. We establish a scale of binding for molecules with different alkyl structures and chain lengths and thereby demonstrate the critical nature of noncovalent van der Waals interactions in determining the selectivity by modulating the stability of key reaction intermediates bound to the surface. The binding hierarchy is the same for Au(111) and Au(110), which demonstrates a relative lack of sensitivity to the surface structure. The hierarchy of binding established in this work provides guiding principles for predicting how molecular structure affects the competition for binding sites more broadly. Besides the nature of the primary surface-molecule bonding, three additional factors that affect the stabilities of the reactive intermediates are clearly established: (1) the number of C atoms in the alkyl chain, (2) the presence of C-C bond unsaturation, and (3) the degree of branching of the alkyl group of the adsorbed molecules. We suggest that this is a fundamental principle that is generally applicable to a broad range of reactions on metal catalysts.

Understanding differences in HIV/HCV prevalence according to differentiated risk behaviors in a sample of PWID in rural Puerto Rico.

BACKGROUND: Blood contained in needles and injection equipment has been identified as a vector for HIV and HCV transmission among people who inject drugs (PWID). Yet, there is often a wide discrepancy in prevalence for both viruses. While microbiological differences between viruses influence prevalence, other variables associated with the way drugs are acquired and used, also play a role. METHODS: Respondent-driven sampling (RDS) methods recruited a sample of 315 current intravenous drug users in rural Puerto Rico. Information about type and frequency of use, HIV and HVC risk behaviors (sharing needles, cookers, cotton, and water), sexual behaviors, and alcohol use was collected. HIV and HCV statuses were assessed via rapid antibody tests. T tests compare means of participants who tested positive (reactive) to those who tested negative. Logistic regression analyses were used to validate the association of the risk factors involved. RESULTS: Tests showed a significant difference in HIV (6%) and HCV (78.4%) prevalence among a population of current PWID. The main risk behaviors in HCV transmission are the sharing of injection "works", (e.g., cookers, cotton, and water). Sharing works occurred more than twice as often as the sharing of needles, and HCV+ and HCV- individuals reported the same needle sharing habits. CONCLUSIONS: Washing and rinsing injection works with water seems to prevent HIV transmission, but it is unable to prevent HCV infection. While education about the need to clean injection equipment with bleach might be beneficial, equipment sharing--and the subsequent risk of HVC--might be unavoidable in a context where participants are forced to pool resources to acquire and use intravenous drugs.

Demographic and High-Risk Behaviors associated with HPV and HPV Vaccine Awareness among Persons Aged 15-74 Years in Puerto Rico.

OBJECTIVE: Studies of human papillomavirus (HPV) awareness in Puerto Rico (PR) are limited and are of interest given low HPV vaccine uptake in this population. This cross-sectional study aimed to determine factors associated to HPV and HPV vaccine awareness among persons aged 15-74 years living in Puerto Rico. METHODS: We analysed data from a sub-sample of 1,476 men and women who participated in a 2008 population-based island-wide household survey and who completed an HPV module. Multivariate logistic regression models were used to examine factors associated with HPV and HPV vaccine awareness. RESULTS: Overall, 37.2% of participants had heard about HPV and 33.4% had heard of the vaccine. Multivariate logistic regression showed that women were more likely to have heard of HPV (OR adjusted: 4.54; 95% CI=3.45, 5.98) or of the HPV vaccine (OR adjusted: 6.15; 95% CI=4.50, 8.40) as compared to men. HPV awareness was also lower among older adults, persons with lower income and with lower educational attainment, those without children and smokers (p < 0.05). CONCLUSION: In 2008, two years after the introduction of the first HPV vaccine in PR and the US, public awareness about HPV infection and the HPV vaccine was lower in Hispanics in PR as compared to other populations. Identified high-risk populations should be targeted in preventive care strategies. Future efforts should increase HPV knowledge and vaccine use in this population in order to maximize the impact of vaccination programs.

Van der Waals interactions determine selectivity in catalysis by metallic gold.

To achieve high selectivity for catalytic reactions between two or more reactants on a heterogeneous catalyst, the relative concentrations of the reactive intermediates on the surface must be optimized. If species compete for binding sites, their concentrations depend on their relative binding strengths to the surface. In this article we describe a general framework for predicting the relative stability of organic intermediates involved in oxygen-assisted reactions on metallic gold with broad relevance to catalysis by metals. Combining theory and experiment, we establish that van der Waals interactions between the reactive intermediates and the surface, although weak, determine relative stabilities and thereby dictate the conditions for optimum selectivity. The inclusion of these interactions is essential for predicting these trends. The concepts and methods employed here have broad applicability for determining the stability of intermediates on the surfaces of catalytic metals and specifically demonstrate the critical role of weak interactions in determining reaction selectivity among reactions of complex molecules.

Tuning the reactivity of semiconductor surfaces by functionalization with amines of different basicity.

Surface functionalization of semiconductors has been the backbone of the newest developments in microelectronics, energy conversion, sensing device design, and many other fields of science and technology. Over a decade ago, the notion of viewing the surface itself as a chemical reagent in surface reactions was introduced, and adding a variety of new functionalities to the semiconductor surface has become a target of research for many groups. The electronic effects on the substrate have been considered as an important consequence of chemical modification. In this work, we shift the focus to the electronic properties of the functional groups attached to the surface and their role on subsequent reactivity. We investigate surface functionalization of clean Si(100)-2 × 1 and Ge(100)-2 × 1 surfaces with amines as a way to modify their reactivity and to fine tune this reactivity by considering the basicity of the attached functionality. The reactivity of silicon and germanium surfaces modified with ethylamine (CH(3)CH(2)NH(2)) and aniline (C(6)H(5)NH(2)) is predicted using density functional theory calculations of proton attachment to the nitrogen of the adsorbed amine to differ with respect to a nucleophilic attack of the surface species. These predictions are then tested using a model metalorganic reagent, tetrakis(dimethylamido)titanium (((CH(3))(2)N)(4)Ti, TDMAT), which undergoes a transamination reaction with sufficiently nucleophilic amines, and the reactivity tests confirm trends consistent with predicted basicities. The identity of the underlying semiconductor surface has a profound effect on the outcome of this reaction, and results comparing silicon and germanium are discussed.

Are the minimally invasive techniques the new gold standard in thymus surgery for myasthenia gravis? Experience of a reference single-site in VATS thymectomy.

The thymus is the primary lymphoid organ responsible for the maturation and proliferation of T lymphocytes. During the first years of our lives, the activation and inactivation of T lymphocytes occur within the thymus, facilitating the correct maturation of central immunity. Alterations in the positive and negative selection of T lymphocytes have been studied as the possible origins of autoimmune diseases, with Myasthenia Gravis (MG) being the most representative example. Structural alterations in the thymus appear to be involved in the initial autoimmune response observed in MG, leading to the consideration of thymectomy as part of the treatment for the disease. However, the role of thymectomy in MG has been a subject of controversy for many years. Several publications raised doubts about the lack of evidence justifying thymectomy's role in MG until 2016 when a randomized study comparing thymectomy via sternotomy plus prednisone versus prednisone alone was published in the New England Journal of Medicine (NEJM). The results clearly favored the group of patients who underwent surgery, showing improvements in symptoms, reduced corticosteroid requirements, and fewer recurrences over 3 years of follow-up. In recent years, the emergence of less invasive surgical techniques has made video-assisted or robotic-assisted thoracoscopic (VATS/RATS) thymectomy more common, replacing the traditional sternotomy approach. Despite the increasing use of VATS, it has not been validated as a technique with lower morbidity compared to sternotomy in the treatment of MG. The results of the 2016 trial highlighted the benefits of thymectomy, but all the patients underwent surgery via sternotomy. Our hypothesis is that VATS thymectomy is a technique with lower morbidity, reduced postoperative pain, and shorter postoperative hospital stays than sternotomy. Additionally, VATS offers better clinical improvement in patients with MG. The primary objective of this study is to validate the VATS technique as the preferred approach for thymectomy. Furthermore, we aim to analyze the impact of VATS thymectomy on symptoms and corticosteroid dosage in patients with MG, identifying factors that may predict a better response to surgery.

Cytotoxic effects on human dental pulp stem Cells after exposure to adhesive bonding agents.

Studies regarding cytotoxic effects attributed to the use of adhesive bonding agents on pulp tissue are not conclusive. To point out whether these materials are safe for clinical use, in vivo exposure of dental pulp to adhesive bonding agents was simulated using an experimental setup in which Human Dental Pulp Stem Cells (hDPSC) are exposed to the action of two kinds of adhesives: self-etching adhesives and two-step bonding agents through a dentine barrier. Cytotoxic effects on these cells were evaluated by MTT assay protocol and fluorescence microscopy, and their results were contrasted to those obtained through Raman spectra taken on single hDPSCs. Overall, no significant cytotoxic effects were observed by combining all the techniques, and cell viability close to 90% was achieved for a dentine barrier of at least 1 mm thick. Moreover, Raman spectroscopy was able to detect structural DNA damage in some dental pulp cells when exposed to two-step bonding agents, suggesting that this technique could be considered a complementary tool with the potential to evaluate cell toxicity beyond cell viability.

Descending necrotizing mediastinitis: key points to reduce the high associated mortality in a consecutive case series.

Background: Descending necrotizing mediastinitis (DNM) is an acute life-threatening infection that originates in the oropharyngeal region. It is an uncommon disease with a mortality rate of about 20-40%. This high mortality is mainly attributed to delays in diagnosis and treatment and poor drainage of the mediastinum. We highlight key points that may help reduce mortality. Case Description: We analyze a retrospective case series of seven patients diagnosed with DNM between March 2019 and July 2022 at Hospital de la Santa Creu i Sant Pau. The primary oropharyngeal infection was peritonsillar abscess in three cases and odontogenic abscess in four. All patients showed symptoms of severe cervical infection and symptoms suggestive of mediastinitis. A cervicothoracic computed tomography (CT) scan confirmed the presence of cervical and mediastinal collections and emphysema in all cases. All patients were simultaneously evaluated by the otorhinolaryngology and thoracic surgery teams. Broad-spectrum antibiotic therapy was instituted pending culture. All the patients underwent urgent surgery, consisting of cervicotomy to control the cervical focus and unilateral or bilateral video-assisted thoracoscopic debridement and drain of the pleural cavities and mediastinum. Regarding the outcomes, no patients died, one patient (14.2%) underwent transcervical mediastino-thoracoscopy drainage only. In six patients (85.8%) we performed a combined transcervical and transthoracic approach. Reoperation was required in 3 (43%) cases. The parameter that indicated a poor clinical evolution in these patients was an increase in C-reactive protein and the infection extension on the cervicothoracic CT scan. The follow-up was 30 days from last surgery; there were no losses. Conclusions: Based on our experience, the key points that can help reduce the high mortality associated with DNM are a rapid multidisciplinary assessment and a combined surgical procedure, considering the minimally invasive approach as the first option to drain the pleural cavities and mediastinum.