Evaluation of clinical practice guideline-derived clinical decision support systems using a novel quality model.

Over the last decade, clinical practice guidelines (CPGs) have become an important asset for daily life in healthcare organizations. Efficient management and digitization of CPGs help achieve organizational objectives and improve patient care and healthcare quality by reducing variability. However, digitizing CPGs is a difficult, complex task because they are usually expressed as text, and this often leads to the development of partial software solutions. At present, different research proposals and CPG-derived CDSS (clinical decision support system) do exist for managing CPG digitalization lifecycles (from modeling to deployment and execution), but they do not all provide full lifecycle support, making it more difficult to choose solutions or proposals that fully meet the needs of a healthcare organization. This paper proposes a method based on quality models to uniformly compare and evaluate technological tools, providing a rigorous method that uses qualitative and quantitative analysis of technological aspects. In addition, this paper also presents how this method has been instantiated to evaluate and compare CPG-derived CDSS by highlighting each phase of the CPG digitization lifecycle. Finally, discussion and analysis of currently available tools are presented, identifying gaps and limitations.

Association between Asymptomatic Hyperuricemia with Adiposity Indices: A Cross-Sectional Study in a Spanish Population.

INTRODUCTION: New anthropometric indices have been developed as an alternative to body mass index (BMI) and waist circumference (WC) to assess body mass and visceral fat. Asymptomatic hyperuricemia is considered an independent cardiovascular risk factor. Currently, little is known about the relationship between asymptomatic hyperuricemia and several new anthropometric indices. This study aimed to assess the association between the presence of asymptomatic hyperuricemia and anthropometric indices, both novel and traditional. METHODS: This study analyzed 1094 Spanish subjects who consecutively visited the cardiovascular risk consultation of the University Hospital San Pedro de Alcántara of Cáceres, Spain, between June 2021 and September 2022. Anthropometric measures, including traditional and novel indices, were determined. The asymptomatic hyperuricemia group was defined according to serum uric acid levels. RESULTS: All the anthropometric indices studied, including new and traditional, were significantly greater among patients with asymptomatic hyperuricemia, except for WWI. In multiple linear regression analysis, serum uric acid levels were significantly correlated with BMI, WHR, WHtR, AVI, BAI, BRI, CUN-BAE, and WWI but not ABSI or CI. In the univariate analysis, all indices were associated with asymptomatic hyperuricemia (p < 0.05); however, only WHtR (adjusted OR: 2.93; 95% CI: 1.03-8.37; p = 0.044), AVI (adjusted OR: 1.46; 95% CI: 1.04-2.04; p = 0.026), and BRI (adjusted OR: 1.66; 95% CI: 1.19-2.32; p = 0.003) were significantly associated in multivariate analysis. Finally, WHtR, AVI, and BRI provided the largest AUCs. CONCLUSIONS: Our findings showed that WHtR, AVI, and BRI were independently positively associated with asymptomatic hyperuricemia and could be good predictors.

A prospective observational concordance study to evaluate computational model-driven clinical practice guidelines for Type 2 diabetes mellitus.

BACKGROUND: Clinical Practice Guidelines (CPGs) provide healthcare professionals with performance and decision-making support during the treatment of patients. Sometimes, however, they are poorly implemented. The IDE4ICDS platform was developed and validated with CPGs for type 2 diabetes mellitus (T2DM). OBJECTIVE: The main objective of this paper is to present the results of the clinical validation of the IDE4ICDS platform in a real clinical environment at two health clinics in the Andalusian Public Health System (SSPA) in the southern Spanish region of Andalusia. METHODS: National and international knowledge sources on T2DM were selected and reviewed and used to define a diabetes CPG model on the IDE4ICDS platform. Once the diabetes CPG was configured and deployed, it was validated. A total of 506 patients were identified as meeting the inclusion criteria, of whom 130 could be recruited and 89 attended the appointment. RESULTS: A concordance analysis was performed with the kappa value. Overall agreement between the recommendations provided by the system and those recorded in each patient's EHR was good (0.61 - 0.80) with a total kappa index of 0.701, leading to the conclusion that the system provided appropriate recommendations for each patient and was therefore well-functioning. CONCLUSIONS: A series of possible improvements were identified based on the limitations for the recovery of variables related to the quality of these recolected variables, the detection of duplicate recommendations based on different input variables for the same patient, and clinical usability, such as the capacity to generate reports based on the recommendations generated. Nevertheless, the project resulted in the IDE4ICDS platform: a Clinical Decision Support System (CDSS) capable of providing appropriate recommendations for improving the management and quality of patient care and optimizing health outcomes. The result of this validation is a safe and effective pathway for developing and adopting digital transformation at the regional scale of the use of biomedical knowledge in real healthcare.

Molecular Characterization of Trypanosoma cruzi Reactivation and Follow-up in a Case Series of People With HIV.

We characterize Trypanosoma cruzi infections from blood and cerebrospinal fluid samples in a case series of people with human immunodeficiency virus and Chagas disease. We identify different infecting T. cruzi populations, highlighting the usefulness of real-time polymerase chain reaction for Chagas disease reactivation diagnosis and evaluation of treatment response.

Relationship between the novel and traditional anthropometric indices and subclinical atherosclerosis evaluated by carotid intima-media thickness (c-IMT).

Introduction: Over the last few years, novel anthropometric indices have been developed as an alternative to body mass index (BMI) and other traditional anthropometric measurements to enhance the estimate of fat proportion and its relationship to a future cardiovascular event. The purpose of this study was to investigate the association of carotid intima-media thickness (c-IMT) estimated by Doppler ultrasound with current anthropometric indices (traditional and novel). Methods: A cross-sectional study was conducted on a total of 789 Spanish patients. Traditional (BMI, WHR, and WHtR) and new (WWI, AVI, ABSI, BRI, BAI, CUN-BAE, and CI) anthropometric indices were determined, and carotid Doppler ultrasound was performed to evaluate c-IMT (≥0.90 mm). Results: Most of the anthropometric indices analyzed were significantly higher among patients with pathological c-IMT, except for BMI, BAI, and CUN-BAE. In multiple linear regression analysis, c-IMT was positively related to ABSI, AVI, BRI, CI, and WWI but not to CUN-BAE, BAI, or traditional anthropometric indices. Similarly, in univariate analysis, all indices were associated with a c-IMT of ≥0.90 mm (p < 0.05), except BMI, BAI, and CUN-BAE; however, only ABSI (adjusted OR: 1.61; 95% CI: 1.08-2.40; p = 0.017), CI (adjusted OR: 1.73; 95% CI: 1.15-2.60; p = 0.008), and WWI (adjusted OR: 1.74; 95% CI: 1.14-2.64; p = 0.009) were significantly associated in multivariate analysis. Finally, CI, ABSI, and WWI provided the largest AUC, and BMI and CUN-BAE showed the lowest AUC. Conclusion: ABSI, CI, and WWI were positively associated with pathological c-IMT (≥0.90 mm), independent of other confounders.

Antihypertensive medication use during pregnancy in a real-world cohort of patients diagnosed with a hypertensive disorder of pregnancy.

Hypertensive disorders of pregnancy (HDP) are rising in prevalence and associated with adverse maternal and infant health outcomes. Current guidelines recommend labetalol, nifedipine, and methyldopa as acceptable first-line agents to treat HDP in outpatient settings. However, the current practice regarding antihypertensive medication usage and selection remain unclear. A retrospective, observational cohort study was conducted in 1,641 patients with a physician diagnosis of HDP who delivered at two academic medical centers in North Carolina from 2014 to 2017. Use of any antihypertensive medication, and the agent selected, at any encounter during pregnancy or on the delivery date was collected from the electronic health record. Proportions were compared across HDP diagnosis (eclampsia/severe preeclampsia, chronic hypertension with superimposed preeclampsia, preeclampsia, gestational hypertension) by Chi-square tests and multivariable logistic regression. Antihypertensive medications were used in 1,276 (77.8%) patients overall. Among treated patients, labetalol (74.9%) was the most frequently used medication followed by nifedipine (29.6%) and hydralazine (20.5%). Methyldopa was used infrequently (4.4%). HDP type was the strongest factor associated with use of an antihypertensive agent. Relative to gestational hypertension, antihypertensive use was significantly more likely [odds ratio (95% CI)] in patients with severe preeclampsia [5.94 (3.85-9.16)], chronic hypertension with superimposed preeclampsia [4.99 (3.46-7.19)], and preeclampsia [2.13 (1.61-2.82)]. In a real-world setting, antihypertensive medication use among HDP patients was common, labetalol, nifedipine, and hydralazine were the most commonly selected agents, and increasing HDP severity was associated with a higher likelihood of antihypertensive use. Future studies comparing medication effectiveness in pregnant patients with distinct HDP diagnoses are needed.

Acute colonic pseudo-obstruction syndrome in patients with severe COVID-19 in Buenos Aires, Argentina.

BACKGROUND: Several gastrointestinal complications have been reported in patients with COVID-19, including motility disorders, such as acute colonic pseudo-obstruction (ACPO). This affection is characterized by colonic distention in the absence of mechanical obstruction. ACPO in the context of severe COVID-19 may be related to neurotropism and direct damage of SARS-CoV-2 in enterocytes. METHOD: We conducted a retrospective study of patients who were hospitalized for critical COVID-19 and developed ACPO between March 2020 and September 2021. The diagnostic criteria to define ACPO was the presence of 2 or more of the following: abdominal distension, abdominal pain, and changes in the bowel movements, associated with distension of the colon in computed tomography. Data of sex, age, past medical history, treatment, and outcomes were collected. RESULTS: Five patients were detected. All required admission to the Intensive Care Unit. The ACPO syndrome developed with a mean of 33.8 days from the onset of symptoms. The mean duration of the ACPO syndrome was 24.6 days. The treatment included colonic decompression with placement of rectal and nasogastric tubes, endoscopy decompression in two patients, bowel rest, fluid, and electrolytes replacement. One patient died. The remaining resolved the gastrointestinal symptoms without surgery. CONCLUSIONS: ACPO is an infrequent complication in patients with COVID-19. It occurs especially in patients with critical condition, who require prolonged stays in intensive care and multiple pharmacological treatments. It is important to recognize its presence early and thus establish an appropriate treatment, since the risk of complications is high.

Social Learning versus Individual Learning in the Division of Labour.

Division of labour, or the differentiation of the individuals in a collective across tasks, is a fundamental aspect of social organisations, such as social insect colonies. It allows for efficient resource use and improves the chances of survival for the entire collective. The emergence of large inactive groups of individuals in insect colonies sometimes referred to as laziness, has been a puzzling and hotly debated division-of-labour phenomenon in recent years that is counter to the intuitive notion of effectiveness. It has previously been shown that inactivity can be explained as a by-product of social learning without the need to invoke an adaptive function. While highlighting an interesting and important possibility, this explanation is limited because it is not yet clear whether the relevant aspects of colony life are governed by social learning. In this paper, we explore the two fundamental types of behavioural adaptation that can lead to a division of labour, individual learning and social learning. We find that inactivity can just as well emerge from individual learning alone. We compare the behavioural dynamics in various environmental settings under the social and individual learning assumptions, respectively. We present individual-based simulations backed up by analytic theory, focusing on adaptive dynamics for the social paradigm and cross-learning for the individual paradigm. We find that individual learning can induce the same behavioural patterns previously observed for social learning. This is important for the study of the collective behaviour of social insects because individual learning is a firmly established paradigm of behaviour learning in their colonies. Beyond the study of inactivity, in particular, the insight that both modes of learning can lead to the same patterns of behaviour opens new pathways to approach the study of emergent patterns of collective behaviour from a more generalised perspective.

Genetic basis for the biodegradation of a polyether-polyurethane-acrylic copolymer by a landfill microbial community inferred by metagenomic deconvolution analysis.

Plastic accumulation in the world amounts to approximately 8300 million tons. Polyurethanes (PU) account for 7.7 % of total plastics production worldwide, and their diverse chemical composition makes them highly recalcitrant to biodegradation. Several works have reported polyurethane-degrading microbial communities. However, it is still necessary to learn more about the chemical, biochemical, and genetic bases linked to the polyurethanolytic phenotype and the microbial taxonomic determinants responsible for metabolizing the PU polymer and its associated chemical additives. To shed light on this problem, we applied physical, chemical, biochemical, metagenomic, and bioinformatic analyses to explore the biodegradation capability and related biochemical and genetic determinants of the BP6 microbial community that can grow in PolyLack, a commercial coating containing a polyether polyurethane acrylate (PE-PU-A) copolymer and several additives, as sole carbon source. We observed complete additives (isopropanol, N-methyl-2-pyrrolidone, 2-butoxyethanol, alkyl glycol ethers) biodegradation and the appearance of released polymer components (toluene diisocyanate (TDI) and methylene diphenyl diisocyanate (MDI) derivatives), and multiple degradation products since early cultivation times. The Hi-C metagenomic analysis identified a complex microbiome with 35 deconvolved Metagenome-Assembled Genomes (MAGs) - several new species - and biodegradation markers that suggest the coexistence of hydrolytic, oxidative, and reductive metabolic strategies for degrading the additives and the PU copolymer. This work also provides evidence of the metabolic capability the BP6 community has for biodegrading polyether polyurethane foams. Based on these analyses, we propose a novel metabolic pathway for 4,4'-methylenedianiline (MDA), an initial biodegradation intermediate of MDI-based PU, encoded in the complex BP6 community metagenome and suggest that this community is a potential biotechnological tool for PU bio-recycling.

Metabolic Performance and Fate of Electrons during Nitrate-Reducing Fe(II) Oxidation by the Autotrophic Enrichment Culture KS Grown at Different Initial Fe/N Ratios.

Autotrophic nitrate-reducing Fe(II)-oxidizing (NRFeOx) microorganisms fix CO2 and oxidize Fe(II) coupled to denitrification, influencing carbon, iron, and nitrogen cycles in pH-neutral, anoxic environments. However, the distribution of electrons from Fe(II) oxidation to either biomass production (CO2 fixation) or energy generation (nitrate reduction) in autotrophic NRFeOx microorganisms has not been quantified. We therefore cultivated the autotrophic NRFeOx culture KS at different initial Fe/N ratios, followed geochemical parameters, identified minerals, analyzed N isotopes, and applied numerical modeling. We found that at all initial Fe/N ratios, the ratios of Fe(II)oxidized to nitratereduced were slightly higher (5.11 to 5.94 at Fe/N ratios of 10:1 and 10:0.5) or lower (4.27 to 4.59 at Fe/N ratios of 10:4, 10:2, 5:2, and 5:1) than the theoretical ratio for 100% Fe(II) oxidation being coupled to nitrate reduction (5:1). The main N denitrification product was N2O (71.88 to 96.29% at Fe/15N ratios of 10:4 and 5:1; 43.13 to 66.26% at an Fe/15N ratio of 10:1), implying that denitrification during NRFeOx was incomplete in culture KS. Based on the reaction model, on average 12% of electrons from Fe(II) oxidation were used for CO2 fixation while 88% of electrons were used for reduction of NO3- to N2O at Fe/N ratios of 10:4, 10:2, 5:2, and 5:1. With 10 mM Fe(II) (and 4, 2, 1, or 0.5 mM nitrate), most cells were closely associated with and partially encrusted by the Fe(III) (oxyhydr)oxide minerals, whereas at 5 mM Fe(II), most cells were free of cell surface mineral precipitates. The genus Gallionella (>80%) dominated culture KS regardless of the initial Fe/N ratios. Our results showed that Fe/N ratios play a key role in regulating N2O emissions, for distributing electrons between nitrate reduction and CO2 fixation, and for the degree of cell-mineral interactions in the autotrophic NRFeOx culture KS. IMPORTANCE Autotrophic NRFeOx microorganisms that oxidize Fe(II), reduce nitrate, and produce biomass play a key role in carbon, iron, and nitrogen cycles in pH-neutral, anoxic environments. Electrons from Fe(II) oxidation are used for the reduction of both carbon dioxide and nitrate. However, the question is how many electrons go into biomass production versus energy generation during autotrophic growth. Here, we demonstrated that in the autotrophic NRFeOx culture KS cultivated at Fe/N ratios of 10:4, 10:2, 5:2, and 5:1, ca. 12% of electrons went into biomass formation, while 88% of electrons were used for reduction of NO3- to N2O. Isotope analysis also showed that denitrification during NRFeOx was incomplete in culture KS and the main N denitrification product was N2O. Therefore, most electrons stemming from Fe(II) oxidation seemed to be used for N2O formation in culture KS. This is environmentally important for the greenhouse gas budget.

Explaining workers' inactivity in social colonies from first principles.

Social insects are among the ecologically most successful collectively living organisms, with efficient division of labour a key feature of this success. Surprisingly, these efficient colonies often have a large proportion of inactive workers in their workforce, sometimes referred to as lazy workers. The dominant hypotheses explaining this are based on specific life-history traits, specific behavioural features or uncertain environments where inactive workers can provide a 'reserve' workforce that can spring into action quickly. While there is a number of experimental studies that show and investigate the presence of inactive workers, mathematical and computational models exploring specific hypotheses are not common. Here, using a simple mathematical model, we show that a parsimonious hypothesis can explain this puzzling social phenomenon. Our model incorporates social interactions and environmental influences into a game-theoretical framework and captures how individuals react to environment by allocating their activity according to environmental conditions. This model shows that inactivity can emerge under specific environmental conditions as a by-product of the task allocation process. Our model confirms the empirical observation that in the case of worker loss, prior homeostatic balance is re-established by replacing some of the lost force with previously inactive workers. Most importantly, our model shows that inactivity in social colonies can be explained without the need to assume an adaptive function for this phenomenon.

Prevalence of pulp canal obliteration and periapical pathology in human anterior teeth: A three-dimensional analysis based on CBCT scans.

This study aimed to determine the prevalence of pulp canal obliteration (PCO) and its association with periapical pathology (Hypodense areas) in cone-beam computed tomography (CBCT) scans of anterior teeth. A total of 2161 CBCT scans from patients 18 years or older taken between 2000 and 2020 were selected. Patient-, tooth- and scan-related data were registered. Two calibrated evaluators recorded the number of teeth with PCO ≥4 mm in the cervical third of the roots and the presence or absence of periapical hypodensities (PH). The length of the root canal that was calcified was also determined. Logistic regression analysis was used to determine whether any of the recorded factors influenced the presence of PCO and the presence of periapical pathology in teeth presenting with PCO. The only factor significantly related to the presence of PCO was patient age. The prevalence of PH in teeth exhibiting PCO was 10%.

Optimal Control of all Modifiable Vascular Risk Factors Among Patients With Atherosclerotic Disease. A Real-Life Study.

The effects of maintaining all classical, vascular risk factors on target among patients with stabilized atherosclerotic cardiovascular disease (ASCVD) are uncertain. Factores de Riesgo y ENfermedad Arterial (FRENA) was a prospective registry of consecutive outpatients with coronary, cerebrovascular, or peripheral artery disease. We analyzed the incidence of recurrent events and mortality according to sustained, optimal control of principal risk factors including the following: LDL cholesterol, glucose, blood pressure, and smoking. As of December 2018, 4285 stable outpatients were eligible for this study. Over a median follow-up of 21 months, 664 (15%) maintained all risk factors on target (Group 1), while 3621 (85%) did not (Group 2). During follow-up, no differences in recurrent major adverse cardiovascular events (MACEs) or death were observed between groups. On multivariable analysis, patients with previous known dyslipidemia (hazard ratio [HR]: 95% confidence interval (95% CI): ([HR]: 1.20 [95% CI, 1.03-1.40]), polyvascular disease ([HR]: 1.98 [95% CI, 1.69-2.32]), insulin therapy ([HR]: 1.56 [95% CI, 1.24-1.95]) and associated conditions ([HR]: 1.47 [95% CI, 1.24-1.74]) were associated with a higher risk for subsequent MACE. The presence of associated medical conditions was also strongly associated with all-cause death ([HR]: 3.49 [95% CI, 2.35-5.19]). Only a minority of patients with atherosclerotic cardiovascular disease achieved sustained optimal control for all principal risk factors although without discernible clinical, therapeutic benefit. The findings of the present study provide some insights into what factors may be used to guide physicians in adapting intensive, multifactorial therapy to the individual patient in clinical practice.

Association of Subclinical Carotid Atherosclerosis Assessed by High-Resolution Ultrasound With Traditional and Novel Anthropometric Indices.

Novel anthropometric indices have been proposed as an alternative to body mass index (BMI) and waist circumference (WC) to determine visceral adipose tissue and body mass. Little is known about the relationship of these new anthropometric indices to subclinical carotid atherosclerosis. The objective of this study was to assess the association of anthropometric indices, both new and traditional, with the presence of subclinical carotid artery arteriosclerosis (SCAA) estimated by Doppler ultrasound. This cross-sectional study analyzed 788 Spanish patients who consecutively attended a vascular risk consultation between June 2021 and September 2022. Traditional anthropometric indices (BMI, WHR and WHtR) and novel indices (ABSI, AVI, BAI, BRI, CI, CUNBAE and WWI) were calculated, and Doppler ultrasound in the carotid artery (cIMT and atherosclerosis plaque) was performed to detect SCAA. All analyzed anthropometric indices, except BMI, BAI and CUNBAE, were significantly higher in patients with SCAA. ABSI, BRI, CI, WHR, WHtR and WWI and were associated with SCAA in the univariate analysis (p<0.05); however, only ABSI (adjusted OR: 1.15; 95% CI: 1.10-2.38; p= 0.042) was significantly associated with SCAA in the multivariate analysis. In conclusion, only ABSI was significantly positively associated with SCAA, independent of other confounders.

Protein Kinase G2 Is Essential for Skeletal Homeostasis and Adaptation to Mechanical Loading in Male but Not Female Mice.

We previously showed that the NO/cGMP/protein kinase G (PKG) signaling pathway positively regulates osteoblast proliferation, differentiation, and survival in vitro, and that cGMP-elevating agents have bone-anabolic effects in mice. Here, we generated mice with an osteoblast-specific (OB) knockout (KO) of type 2 PKG (gene name Prkg2) using a Col1a1(2.3 kb)-Cre driver. Compared to wild type (WT) littermates, 8-week-old male OB Prkg2-KO mice had fewer osteoblasts, reduced bone formation rates, and lower trabecular and cortical bone volumes. Female OB Prkg2-KO littermates showed no bone abnormalities, despite the same degree of PKG2 deficiency in bone. Expression of osteoblast differentiation- and Wnt/ß-catenin-related genes was lower in primary osteoblasts and bones of male KO but not female KO mice compared to WT littermates. Osteoclast parameters were unaffected in both sexes. Since PKG2 is part of a mechano-sensitive complex in osteoblast membranes, we examined its role during mechanical loading. Cyclical compression of the tibia increased cortical thickness and induced mechanosensitive and Wnt/ß-catenin-related genes to a similar extent in male and female WT mice and female OB Prkg2-KO mice, but loading had a minimal effect in male KO mice. We conclude that PKG2 drives bone acquisition and adaptation to mechanical loading via the Wnt/ß-catenin pathway in male mice. The striking sexual dimorphism of OB Prkg2-KO mice suggests that current U.S. Food and Drug Administration-approved cGMP-elevating agents may represent novel effective treatment options for male osteoporosis. © 2022 American Society for Bone and Mineral Research (ASBMR).

Conclusiones de las XI Jornadas del Grupo Avilés sobre Medicina del Deporte 3 y 4 de Octubre de 2022 (Barcelona) / Conclusões da XI Conferência do Grupo Aviles de Medicina Esportiva, 3 e 4 de outubro de 2022 (Barcelona) / Conclusions of the XI Conference of the Aviles Group on Sports Medicine, October 3 and 4, 2022 (Barcelona)

El Grupo de Trabajo Avilés fue impulsado por el Consejo Superior de Deportes en 2009 y está formado por representantes de los Centros de Medicina dela Educación Física y el Deporte de todas las comunidades autónomas que cuentan con estas infraestructuras y representantes de centros de medicinadel deporte de centros de tecnificación, centros municipales de medicina del deporte y la Agencia Española de Protección de la Salud en el Deporte. Comoobjetivos de este grupo de trabajo figuran la coordinación entre estas estructuras autonómicas de la medicina del deporte, el planteamiento de solucionescomunes a las diferentes problemáticas que sufren cada uno de los centros y el ser un grupo de asesoramiento, en los diferentes ámbitos de la medicinade la educación física y el deporte, para el Consejo Superior de Deportes.Este grupo de trabajo se reúne periódicamente; en su última reunión, celebrada en Barcelona el 3 y 4 de octubre de 2022, se acordaron una serie deconclusiones, en relación a la muerte súbita y las arritmias en el deporte, el SARS Cov-2, la prevención, la salud mental, la diversidad sexual y laespecialidad MIR.(AU)

The Avilés Working Group was promoted by the National Sports Council in 2009 and is made up of representatives of Physical Education and SportsMedicine Centers of all the autonomous communities that have these infrastructures, Sports Technification Centers, municipal Sports Medicine Centersand the Spanish Agency for Health Protection in Sport. The objectives of this working group include the coordination between these autonomousstructures of Sports Medicine, the proposal of common solutions to the different problems suffered by each of the centers and to be an advisory group inthe different areas of the Physical Education and Sports Medicine, for the National Sports Council.This working group meets periodically; at its last online meeting, held in Barcelona on October 3-4, 2022, a series of conclusions were agreed in relationto sudden death and arrytmias in sport, SARS Cov-2, prevention, mental health, sexual diversity and the MIR specialty.(AU)

O grupo de Trabalho Avilés foi incentivado pelo Conselho Superior de Esportes em 2009. É composto por representantes dos Centros de Medicina daEducação Física e Esporte de todas as comunidades autônomas que contam com estas infraestruturas, bem como representantes dos centros de medicinado esporte de centros técnicos, centros municipais de medicina do esporte e da Agencia Espanhola de Proteção da saúde no Esporte. Como objetivos detrabalho desde grupo, figuram a coordenação entre estas estruturas autonômicas da medicina do esporte, a criação de soluções comuns as diferentesproblemáticas que sofrem cada um dos centros, além de ser um grupo de assessoramento, nos diferentes âmbitos da medicina da educação física e doesporte, para o Conselho Superior de Esportes.Este grupo de trabalho se reúne periodicamente; Em sua última reunião, realizada em Barcelona de 3 e 4 de outubro de 2022, foi acordada uma série deconclusões em relação à morte súbita e arritmias no esporte, SARS Cov-2, prevenção, saúde mental, diversidade sexual e especialidade MIR.(AU)

Pathophysiology of Age-Related Macular Degeneration: Implications for Treatment.

Age-related macular degeneration (AMD) is a complex, multifactorial, progressive retinal disease that affects millions of people worldwide and has become the leading cause of visual impairment in developed countries. The disease etiopathogenesis is not understood fully, although many triggers and processes that lead to dysfunction and degeneration of the retinal pigment epithelium (RPE) have already been identified. Thus, the lack of cellular control of oxidative stress, altered proteostasis, dysfunction of lipid homeostasis, and mitochondrial dysfunction form an internal feedback loop that causes the RPE to fail and allows accumulation of abnormal misfolded proteins and abnormal lipids that will form drusen. An inadequate antioxidant response, deficits in autophagy mechanisms, and dysregulation of the extracellular matrix (ECM) help to increase the deposition of abnormal drusen material over time. The drusen then act as inflammatory centers that trigger chronic inflammation of the subretinal space in which microglia and recruited macrophages are also involved, and where the complement system is a key component. Choriocapillaris degeneration and nutritional influences are also classic elements recognized in the AMD pathophysiology. The genetic component of the disease is embodied in the recognition of the described risk or protective polymorphisms of some complement and ECM related genes (mainly CFH and ARMS2/HTRA1). Thus, carriers of the risk haplotype at ARMS2/HTRA1 have a higher risk of developing late AMD at a younger age. Finally, gut microbiota and epigenetics may play a role in modulating the progression to advanced AMD with the presence of local inflammatory conditions. Because of multiple implicated processes, different complex combinations of treatments will probably be the best option to obtain the best visual results; they in turn will differ depending on the type and spectrum of disease affecting individual patients or the disease stage in each patient at a specific moment. This will undoubtedly lead to personalized medicine for control and hopefully find a future cure. This necessitates the continued unraveling of all the processes involved in the pathogenesis of AMD that must be understood to devise the combinations of treatments for different concurrent or subsequent problems.

UBR4/POE facilitates secretory trafficking to maintain circadian clock synchrony.

Ubiquitin ligases control the degradation of core clock proteins to govern the speed and resetting properties of the circadian pacemaker. However, few studies have addressed their potential to regulate other cellular events within clock neurons beyond clock protein turnover. Here, we report that the ubiquitin ligase, UBR4/POE, strengthens the central pacemaker by facilitating neuropeptide trafficking in clock neurons and promoting network synchrony. Ubr4-deficient mice are resistant to jetlag, whereas poe knockdown flies are prone to arrhythmicity, behaviors reflective of the reduced axonal trafficking of circadian neuropeptides. At the cellular level, Ubr4 ablation impairs the export of secreted proteins from the Golgi apparatus by reducing the expression of Coronin 7, which is required for budding of Golgi-derived transport vesicles. In summary, UBR4/POE fulfills a conserved and unexpected role in the vesicular trafficking of neuropeptides, a function that has important implications for circadian clock synchrony and circuit-level signal processing.

Improved prediction of electrical storm in patients with prior myocardial infarction and implantable cardioverter defibrillator.

AIMS: To evaluate predictors of electrical storm (ES), including chronic total occlusion in an infarct-related coronary artery (infarct-related artery CTO, IRACTO), in a cohort of patients with prior myocardial infarction (MI) and implantable cardioverter-defibrillators (ICD). METHODS: Multicenter observational cohort study including 643 consecutive patients with prior MI and a first ICD implanted between 2005 and 2018 at three tertiary hospitals. All the patients included in the study had undergone a diagnostic coronary angiography before ICD implantation. The variable prior ventricular arrhythmias (VA+) was positive in patients with secondary prevention ICDs and in those with at least one appropriate ICD therapy after primary prevention implantation. RESULTS: During a median follow-up of 42 months 59 patients (9%) suffered ES. The presence of at least one IRACTO not revascularized (IRACTO-NR) was associated with a significantly higher cumulative incidence of ES (14.5% vs 4.8%, p < 0.001). IRACTO-NR maintained a significant association with ES after adjustment for potential confounders (HR 2.3, p = 0.005) and was an independent predictor of ES together with VA+ and LVEF. The best cut-off of LVEF to predict ES was ≤38%. A risk-prediction model based on IRACTO-NR, VA+ and LVEF≤38% identified three categories of ES risk (low, intermediate and high), with progressively increasing cumulative incidence of ES (2.2%, 9% and 20%). CONCLUSION: In a cohort of patients with prior MI and ICD, IRACTO-NR is an independent predictor of ES. A new risk-prediction model allowed the identification of three categories of risk, with potentially important clinical implications.

Platelets modulate CD4+ T-cell function in COVID-19 through a PD-L1 dependent mechanism.

Severe COVID-19 is associated with a systemic inflammatory response and progressive CD4+ T-cell lymphopenia and dysfunction. We evaluated whether platelets might contribute to CD4+ T-cell dysfunction in COVID-19. We observed a high frequency of CD4+ T cell-platelet aggregates in COVID-19 inpatients that inversely correlated with lymphocyte counts. Platelets from COVID-19 inpatients but not from healthy donors (HD) inhibited the upregulation of CD25 expression and tumour necrosis factor (TNF)-α production by CD4+ T cells. In addition, interferon (IFN)-γ production was increased by platelets from HD but not from COVID-19 inpatients. A high expression of PD-L1 was found in platelets from COVID-19 patients to be inversely correlated with IFN-γ production by activated CD4+ T cells cocultured with platelets. We also found that a PD-L1-blocking antibody significantly restored platelets' ability to stimulate IFN-γ production by CD4+ T cells. Our study suggests that platelets might contribute to disease progression in COVID-19 not only by promoting thrombotic and inflammatory events, but also by affecting CD4+ T cells functionality.