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[18F]FDG PET/CT in Short-Term Complications of COVID-19: Metabolic Markers of Persistent Inflammation and Impaired Respiratory Function.
No full textSARS-CoV-2 virus infects organs other than the lung, such as mediastinal lymph nodes, spleen, and liver, but, to date, metabolic imaging studies obtained in short-term follow-ups of patients hospitalized with severe COVID-19 infection are rare. Our objective was to evaluate the usefulness of [18F]FDG-PET/CT in the short-term follow-up of patients admitted for COVID-19 pneumonia and to explore the association of the findings with clinical prognostic markers. The prospective study included 20 patients with COVID-19 pneumonia (November 2020-March 2021). Clinical and laboratory test findings were gathered at admission, 48-72 h post-admission, and 2-3 months post-discharge, when [18F]FDG-PET/CT and respiratory function tests were performed. Lung volumes, spirometry, lung diffusion capacity for carbon monoxide (DLCO), and respiratory muscle strength were measured. Volumetric [18F]FDG-PET/CT results were correlated with laboratory and respiratory parameters. Eleven [18F]FDG-PET/CT (55%) were positive, with hypermetabolic mediastinal lymphadenopathy in 90.9%. Mediastinal lesion's SUVpeak was correlated with white cells' count. Eleven (55%) patients had impaired respiratory function, including reduced DLCO (35%). SUVpeak was correlated with %predicted-DLCO. TLG was negatively correlated with %predicted-DLCO and TLC. In the short-term follow-up of patients hospitalized for COVID-19 pneumonia, [18F]FDG-PET/CT findings revealed significant detectable inflammation in lungs and mediastinal lymph nodes that correlated with pulmonary function impairment in more than half of the patients.S
Exploring Next Generation Probiotics for Metabolic and Microbiota Dysbiosis Linked to Xenobiotic Exposure: Holistic Approach.
No full textVariation of gut microbiota in metabolic diseases seems to be related to dysbiosis induced by exposure to multiple substances called Microbiota Disrupting Chemicals (MDCs), which are present as environmental and dietary contaminants. Some recent studies have focused on elucidating the alterations of gut microbiota taxa and their metabolites as a consequence of xenobiotic exposures to find possible key targets involved in the severity of the host disease triggered. Compilation of data supporting the triad of xenobiotic-microbiota-metabolic diseases would subsequently allow such health misbalances to be prevented or treated by identifying beneficial microbe taxa that could be Next Generation Probiotics (NGPs) with metabolic enzymes for MDC neutralisation and mitigation strategies. In this review, we aim to compile the available information and reports focused on variations of the main gut microbiota taxa in metabolic diseases associated with xenobiotic exposure and related microbial metabolite profiles impacting the host health status. We performed an extensive literature search using SCOPUS, Web of Science, and PubMed databases. The data retrieval and thorough analyses highlight the need for more combined metagenomic and metabolomic studies revealing signatures for xenobiotics and triggered metabolic diseases. Moreover, metabolome and microbiome compositional taxa analyses allow further exploration of how to target beneficial NGP candidates according to their alleged variability abundance and potential therapeutic significance. Furthermore, this holistic approach has identified limitations and the need of future directions to expand and integrate key knowledge to design appropriate clinical and interventional studies with NGPs. Apart from human health, the beneficial microbes and metabolites identified could also be proposed for various applications under One Health, such as probiotics for animals, plants and environmental bioremediation.S
Molecular stratification of arrhythmogenic mechanisms in the Andersen Tawil Syndrome.
No full textAndersen Tawil Syndrome (ATS) is a rare inheritable disease associated with loss-of-function mutations in KCNJ2, the gene coding the strong inward rectifier potassium channel Kir2.1, which forms an essential membrane protein controlling cardiac excitability. ATS is usually marked by a triad of periodic paralysis, life-threatening cardiac arrhythmias and dysmorphic features, but its expression is variable and not all patients with a phenotype linked to ATS have a known genetic alteration. The mechanisms underlying this arrhythmogenic syndrome are poorly understood. Knowing such mechanisms would be essential to distinguish ATS from other channelopathies with overlapping phenotypes and to develop individualized therapies. For example, the recently suggested role of Kir2.1 as a countercurrent to sarcoplasmic calcium reuptake might explain the arrhythmogenic mechanisms of ATS and its overlap with catecholaminergic polymorphic ventricular tachycardia (CPVT). Here we summarize current knowledge on the mechanisms of arrhythmias leading to sudden cardiac death in ATS. We first provide an overview of the syndrome and its pathophysiology, from the patient´s bedside to the protein, and discuss the role of essential regulators and interactors that could play a role in cases of ATS. The review highlights novel ideas related to some post-translational channel interactions with partner proteins that might help define the molecular bases of the arrhythmia phenotype. We then propose a new all-embracing classification of the currently known ATS loss-of-function mutations according to their position in the Kir2.1 channel structure and their functional implications. We also discuss specific ATS pathogenic variants, their clinical manifestations and treatment stratification. The goal is to provide a deeper mechanistic understanding of the syndrome toward the development of novel targets and personalized treatment strategies
Vol. 27, nº 13. Estrategia de vigilancia y control frente a COVID-19 tras la fase aguda de la pandemia
No full textEnfermedades de Declaración Obligatoria por provincias. Semana 12/2022 y acumulado desde semana 01/2022. Datos provisionales. Incluye además el artículo titulado 'Estrategia de vigilancia y control frente a COVID-19 tras la fase aguda de la pandemia', de Servicio de Vigilancia y Salud Laboral.Ye
Comparación entre cinco técnicas de PCR para el diagnóstico del SARS-CoV-2.
No full textSince the first cases of SARS-CoV-2 appeared, there have been numerous techniques that have been developed for the diagnosis or monitoring of infection, both direct and serological techniques. Choosing a good diagnostic tool is essential for epidemiological control. The objective was to compare five commercialized RT-PCR techniques in real time, in sensitivity, specificity and agreement for the detection of SARS-CoV-2. Five commercial RT-PCR kits for the detection of SARS-CoV-2 were compared. Eight known positive samples were taken and subjected to seven different dilutions or concentrations, and another 135 negative samples were used to determine sensitivity, specificity, and agreement values. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the Palex, Roche and GeneXpert techniques with respect to Seegene were identical, corresponding to 98.21%, 100%, 100% and 99.26% respectively. For Becton Dickinson the sensitivity was 89.28%, the specificity of 100%, the PPV of 100% and the NPV of 95.74%. The agreement using the Kappa index for Palex, Roche and GeneXpert was 0.9892, while the agreement for Becton Dickinson was with a Kappa index of 0.9215. All commercial RT-PCR kits had high sensitivities and specificities, as well as PPV, NPV, and concordance
Standards for practical intravenous rapid drug desensitization & delabeling: A WAO committee statement
No full textDrug hypersensitivity reactions (DHRs) to intravenous drugs can be severe , might leave pa-tients and doctors in a difficult position where an essential treatment or intervention has to be suspended. Even if virtually any intravenous medication can potentially trigger a life-threatening DHR, chemotherapeutics, biologics , antibiotics are amongst the intravenous drugs most frequently involved in these reactions. Admittedly, suspending such treatments may negatively impact the survival outcomes or the quality of life of affected patients. Delabeling pathways and rapid drug desensitization (RDD) can help reactive patients stay on first -choice therapies instead of turning to less efficacious, less cost-effective, or more toxic alternatives. However, these are high-complexity and high-risk techniques, which usually need expert teams and allergy-specific techniques (skin testing, in vitro testing, drug provocation testing) to ensure safety, an accurate diagnosis, and personalized management. Unfortunately, there are significant inequalities within and among countries in access to allergy departments with the necessary expertise and resources to offer these techniques and tackle these DHRs optimally. The main objective of this consensus document is to create a great benefit for patients worldwide by aiding allergists to expand the scope of their practice and support them with evidence, data, and experience from leading groups from around the globe. This statement of the Drug Hypersensitivity Committee of the World Allergy Organization (WAO) aims to be a comprehensive practical guide on the technical aspects of implementing acute-onset intravenous hypersensitivity delabeling and RDD for a wide range of drugs. Thus, the manuscript does not only focus on clinical pathways. Instead, it also provides guidance on topics usually left unaddressed, namely, internal validation, continuous quality improvement, creating a healthy multidisciplinary environment, and redesigning care (including a specific supplemental section on a real-life example of how to design a dedicated space that can combine basic and complex diagnostic and therapeutic techniques in allergy).S
CROSS-SECTIONAL OBSERVATIONAL AND MULTICENTER STUDY FOR THE VALIDATION OF THE SPANISH VERSION OF THE PURE-4 QUESTIONNAIRE
No full textEffect of an Interdisciplinary Weight Loss and Lifestyle Intervention on Obstructive Sleep Apnea Severity: The INTERAPNEA Randomized Clinical Trial.
No full textObesity is the leading cause of obstructive sleep apnea (OSA); however, the effects of weight loss and lifestyle interventions on OSA and comorbidities remain uncertain. To evaluate the effect of an interdisciplinary weight loss and lifestyle intervention on OSA and comorbidities among adults with moderate to severe OSA and overweight or obesity. The Interdisciplinary Weight Loss and Lifestyle Intervention for OSA (INTERAPNEA) study was a parallel-group open-label randomized clinical trial conducted at a hospital-based referral center in Granada, Spain, from April 1, 2019, to October 23, 2020. The study enrolled 89 Spanish men aged 18 to 65 years with moderate to severe OSA and a body mass index (calculated as weight in kilograms divided by height in meters squared) of 25 or greater who were receiving continuous positive airway pressure (CPAP) therapy. The sole inclusion of men was based on the higher incidence and prevalence of OSA in this population, the differences in OSA phenotypes between men and women, and the known effectiveness of weight loss interventions among men vs women. Participants were randomized to receive usual care (CPAP therapy) or an 8-week weight loss and lifestyle intervention involving nutritional behavior change, aerobic exercise, sleep hygiene, and alcohol and tobacco cessation combined with usual care. The primary end point was the change in the apnea-hypopnea index (AHI) from baseline to the intervention end point (8 weeks) and 6 months after intervention. Secondary end points comprised changes in other OSA sleep-related outcomes, body weight and composition, cardiometabolic risk, and health-related quality of life. Among 89 men (mean [SD] age, 54.1 [8.0] years; all of Spanish ethnicity; mean [SD] AHI, 41.3 [22.2] events/h), 49 were randomized to the control group and 40 were randomized to the intervention group. The intervention group had a greater decrease in AHI (51% reduction; change, -21.2 events/h; 95% CI, -25.4 to -16.9 events/h) than the control group (change, 2.5 events/h; 95% CI, -2.0 to 6.9 events/h) at the intervention end point, with a mean between-group difference of -23.6 events/h (95% CI, -28.7 to -18.5 events/h). At 6 months after intervention, the reduction in AHI was 57% in the intervention group, with a mean between-group difference of -23.8 events/h (95% CI, -28.3 to -19.3 events/h). In the intervention group, 18 of 40 participants (45.0%) no longer required CPAP therapy at the intervention end point, and 6 of 40 participants (15.0%) attained complete OSA remission. At 6 months after intervention, 21 of 34 participants (61.8%) no longer required CPAP therapy, and complete remission of OSA was attained by 10 of 34 participants (29.4%). In the intervention vs control group, greater improvements in body weight (change, -7.1 kg [95% CI, -8.6 to -5.5 kg] vs -0.3 kg [95% CI, -1.9 to 1.4 kg]) and composition (eg, change in fat mass, -2.9 kg [95% CI, -4.5 to -1.3 kg] vs 1.4 kg [95% CI, -0.3 to 3.1 kg]), cardiometabolic risk (eg, change in blood pressure, -6.5 mm Hg [95% CI, -10.3 to -2.6 mm Hg] vs 2.2 mm Hg [95% CI, -2.1 to 6.6 mm Hg]), and health-related quality of life (eg, change in Sleep Apnea Quality of Life Index, 0.8 points [95% CI, 0.5-1.1 points] vs 0.1 points [95% CI, -0.3 to 0.4 points]) were also found at the intervention end point. In this study, an interdisciplinary weight loss and lifestyle intervention involving Spanish men with moderate to severe OSA and had overweight or obesity and were receiving CPAP therapy resulted in clinically meaningful and sustainable improvements in OSA severity and comorbidities as well as health-related quality of life. This approach may therefore be considered as a central strategy to address the substantial impact of this increasingly common sleep-disordered breathing condition. ClinicalTrials.gov Identifier: NCT03851653
Effects of rituximab on the inflammatory and pro-thrombotic profiles of non-b cells of the immune and vascular systems of rheumatoid arthritis and systemic lupus erythematosus patients
No full textBackground Treatment with B-cell depletion, including rituximab (RTX), has been proven successful in achieving remission from the active disease in Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) patients. However, the effect of RTX on the Cardiovascular disease (CVD) associated to both autoimmune conditions has not been elucidated yet. The aim of this study was to investigate whether B-cell depletion therapy with RTX has an impact on activation of non-B cells of the immune and vascular systems in the context of CVD in RA and SLE patients Methods The analysis was carried out in plasma and purified leucocytes from 25 subjects, including 12 RA and 13 SLE patients. To evaluate the influence of B-cells depletion on the inflammatory profile of T-cells, purified lymphocytes from 6 RA and 7 SLE patients were treated with RTX (1 µg/ml) for 24 hours. B-cells depletion was assessed by flow cytometry and the changes occurred in the inflammatory profile of T cells were analysed by RT-PCR. The changes promoted in the activity of key intracellular regulators of pro-inflammatory cytokines were analysed by western blot in proteins purified from lymphocytes. In a second set of experiments, supernatants from cultured lymphocytes of 6 RA and 7 SLE patients was added –either, in the presence or in the absence of RTX- to cultured endothelial cells (HUVECs), monocytes, and neutrophils isolated from Healthy Donors (HDs) and incubated for 6 hour. The changes induced in the inflammatory/pro-thrombotic profile of these cells was analysed by RT-PCR. Finally, serum obtained from 6 RA and 6 SLE patients at baseline and after 3 months of therapy with RTX, was added to HUVECs, monocytes, and neutrophils isolated from HDs and the response was analysed by RT-PCRS
An example of adaptation: experience of virtual clinical skills circuits of internal medicine students at the Faculty of Medicine, University of Granada (Spain) during the COVID-19 pandemic.
No full textThe state of alarm declared in Spain in response to the Coronavirus pandemic (COVID-19) has had far-reaching consequences in all areas of life. At the University of Granada's (UGR) Faculty of Medicine, online teaching was implemented immediately without any preexisting plan. Second-year undergraduates in medicine, particularly those enrolled in the subject 'Bases of Internal Medicine,' would normally undergo clinical skills circuits in face-to-face group settings. To facilitate undergraduates' acquisition of specific transversal skills by means of an integrated online working system. Before the pandemic, teaching/learning methods consisted of 1) face-to-face group work; 2) teletutoring; 3) written work uploaded to the PRADO online platform for marking by the teletutor; and 4) presentation of written work to the group. As a result of the lockdown, presentations in class were suspended and replaced by online presentations. The means adopted by students in online presentations were freely chosen using various communication techniques: linear projection systems (6); acting/simulation (4); dramatization (1); and role-playing (1). The number of online clinical skills circuits developed was 12, one for each of the clinical skills circuits established for imparting this subject. A total of 12 presentations were made by the 10 groups, each lasting 15 minutes followed by a 5-minute discussion to settle any questions raised. The presentations were marked jointly by the teaching staff, coordinator, and students. The transference of classroom learning to the online environment proved an essential resource for teaching/learning clinical/practical skills during the lockdown, which have never before been imparted at distance