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Encefalitis autoinmune tras vacunación e infección por el SARS-CoV-2 en un paciente con narcolepsia de tipo 1.
No full text20.500.12530/87858We present a narcolepsy type 1 patient that develop an autoimmune encephalitis post vaccine and/or a SARS-CoV-2 infection. At 23 years old, the patient was referred to the emergency room with difficult speaking, headache and tremor followed by changes in behavior, autonomic dysfunction, right focal motor seizure and lethargy. He has received seven weeks before mRNA-1273 (Moderna) vaccine followed by a SARS-CoV-2 infection four weeks after vaccination (positive antigen test). The neurological examination was normal (visual fields, cranial nerves, motor, sensory and reflexes). Nasopharyngeal swab polymerase chain reaction (PCR) testing for COVID-19 was negative. Cerebrospinalfluid (CSF) had highly elevated protein and lymphocytic pleocytosis. CSF bacterial and fungal cultures for viral infections were negative. Brain magnetic resonance imaging (MRI) showed no abnormality on the non-enhanced sequences but the diffusion weighted imaging showed restricted diffusion with high signal on the left hemisphere mainly in the cerebral cortex with a gyro morphology, patched distribution with involvement of the temporal and frontal lobes. Chest, abdomen and pelvis computed tomography; pelvic and scrotum ultrasound, showed no malignancy. Onconeural antibodies were negative. The patient was treated with plasmapheresis and corticosteroids with a good clinical outcome and near complete resolution of the MRI abnormalities. The patient fulfilled the diagnostic criteria for autoimmune encephalitis with subacute onset. COVID-19 infection and vaccination could constitute a risk in a patient with narcolepsy as in this case and, could help to provide better understanding of the implication of immune-mediated processes in the pathophysiology of the diseases
The small MAF transcription factor MAFG co-opts MITF to promote melanoma progression.
No full text20.500.12530/87857Transcription factor deregulation potently drives melanoma progression by dynamically and reversibly controlling gene expression programs. We previously identified the small MAF family transcription factor MAFG as a putative driver of melanoma progression, prompting an in-depth evaluation of its role in melanoma. MAFG expression increases with human melanoma stages and ectopic MAFG expression enhances the malignant behavior of human melanoma cells in vitro, xenograft models, and genetic mouse models of spontaneous melanoma. Moreover, MAFG induces a melanoma phenotype switch from a melanocytic state to a more dedifferentiated state. Mechanistically, MAFG interacts with the lineage transcription factor MITF which is required for the pro-tumorigenic effects of MAFG. MAFG and MITF co-occupy numerous genomic sites and MAFG overexpression influences the expression of genes harboring binding sites for the MAFG~MITF complex. These results establish MAFG as a potent driver of melanomagenesis through dimerization with MITF and uncover an unappreciated mechanism of MITF regulation
National Diagnostic Reference Levels for Standard Descending Thoracic Endovascular Aortic Repair and Optimisation Strategies.
No full text20.500.12530/87908The International Commission on Radiological Protection has highlighted the large number of medical specialties that use fluoroscopy outside diagnostic imaging departments without radiation protection programmes for patients and staff. Vascular surgery is one of these specialties. Thoracic endovascular aortic repair (TEVAR) is a complicated procedure requiring radiation protection guidance and optimisation. The recent EU Basic Safety Standards Directive requires the use and periodic updating of diagnostic reference levels (DRLs) for interventional procedures. The aim of this study was to determine doses for patients undergoing TEVAR with mobile Xray systems and hybrid rooms (fixed Xray systems) to obtain national DRLs and to suggest optimisation actions. This was a retrospective cross sectional study. The Spanish Chapter of Endovascular Surgery conducted a national survey in 11 autonomous communities representing around 77.6% of the Spanish population (47.33 million inhabitants). A total of 266 TEVAR procedures from 17 Spanish centres were analysed, of which 53.0% were performed in hybrid operating rooms. National DRLs were obtained and defined as the third quartile of the median values from the different participating centres. The proposed national DRLs are: for kerma area product (KAP), 113.81 Gy·cm2 for mobile Xray systems and 282.59 Gy·cm2 for hybrid rooms; and for cumulative air kerma (CAK) at the patient entry reference point, 228.38 mGy for mobile systems and 910.64 mGy for hybrid rooms. Based on the requirement to know radiation doses for standard endovascular procedures, this study of TEVARs demonstrated that there is an increased factor of 2.48 in DRLs for KAP when the procedure is performed in a hybrid room compared with mobile C-arm systems, and an increased factor of 3.98 in DRLs for CAK when the procedure is performed with hybrid equipment. These results will help to optimise strategies to reduce radiation doses during TEVAR procedures
Probiotic Supplementation With Saccharomyces boulardii and Enterococcus faecium Improves Gastric Pain and Bloating in Airline Pilots With Chronic Non-atrophic Gastritis: An Open-Label Study.
No full text20.500.12530/87855Background Commercial airline pilots (APs) are prone to upper gastrointestinal symptoms, such as epigastric pain and bloating. These issues are often linked to occupational risk factors like irregular diet, sleep disruption, and circadian rhythm disturbance. The use of probiotics to enhance intestinal health is well established, but their efficacy in treating upper gastrointestinal diseases is still debated. This is primarily due to the stomach's small resident microbiota and its low pH, which is inhospitable to most microbes. However, emerging research suggests that specific probiotic strains, such as Enterococcus faecium, can withstand acidic environments. Moreover, certain yeast species, including Saccharomyces boulardii, can survive at a low pH. Consequently, we conducted a preliminary, three-arm, randomized, open-label, dose-finding, four-week study to compare the effects of watchful waiting (WW) with the administration of an oral probiotic supplement containing S. boulardii and E. faecium in APs diagnosed with Helicobacter pylori-negative chronic non-atrophic gastritis (CNG). Methods The study included 39 APs with CNG who were randomized into three groups with a 1:1:1 ratio. The low-dose group (n = 13) received one capsule of the probiotic supplement twice daily, before meals, for four weeks. The high-dose group (n = 13) was administered two capsules of the supplement on the same schedule. The third group (n = 13) underwent WW and served as the control arm. Blinding was maintained for the examining physicians and laboratory staff, but not for the patients. All participants self-rated their experiences of gastric pain and bloating at the beginning and conclusion of the four-week treatment period. Additionally, serum levels of pepsinogen I (PGI) and pepsinogen II (PGII) were measured at these time points. Results Supplementation with probiotics significantly outperformed WW in reducing subjective gastric pain and bloating. This effect was consistent across both tested dosages, with no significant differences observed. However, only high-dose probiotics led to a statistically significant decrease in PGII levels and an increase in the PGI/PGII ratio after the four-week study period, a result not observed with low-dose probiotics. Conclusions Oral administration of S. boulardii and E. faecium demonstrated potential efficacy in reducing gastric pain and bloating symptoms in APs with CNG, as evidenced by statistically significant symptom improvement compared to the control group that did not receive the probiotic supplementation. Notably, high-dose probiotics resulted in a significant increase in the PGI/PGII ratio, indicating potential long-term cytoprotective effects on the gastric mucosa
Near-infrared II fluorescence imaging
No full textFluorescence imaging in the second near-infrared (NIR-II) window enables deep-tissue imaging with high resolution and improved contrast by taking advantage of the reduced light scattering and tissue autofluorescence in this region of the spectrum. NIR-II fluorescence imaging uses photoluminescent contrast agents - including carbon nanotubes, quantum dots, rare earth-doped nanocrystals, gold nanoclusters, small molecules and their aggregates - and fluorescent proteins, which all exhibit fluorescence in the 1,000-3,000 nm range. After administration of these fluorophores in vivo, live animals can be imaged with specialized detectors and optical instruments, yielding images with contrast and resolution unparalleled by conventional visible and near-infrared fluorescence imaging. This powerful approach enables dynamic imaging of vascular structures and haemodynamics; molecular imaging and image-guided surgery of tumours; and visualization of deep-seated structures, such as the gastrointestinal system. NIR-II fluorescence imaging has revolutionized biomedical imaging over the past 15 years and is poised to make comparable advancements in cardiology, neurobiology and gastroenterology. This Primer describes the principles of NIR-II fluorescence imaging, reviews the most used fluorophores, outlines implementation approaches and discusses specific scientific and clinical applications. Furthermore, the limitations of NIR-II fluorescence imaging are addressed and future opportunities across various scientific domains are explored.Deep tissues can be imaged with high resolution and greater contrast by performing fluorescence imaging in the second near-infrared (NIR-II) window. This Primer summarizes how NIR-II fluorescence imaging can be used in animal models, exploring commonly used fluorophores and implementation approaches across a range of scientific and clinical applications
Persistence in the Methadone Maintenance Program and Its Relationship with the Medication Regimen Complexity Index in Opioid-Dependent Patients
No full text20.500.12530/87893It has been shown that the Medication Regimen Complexity Index (MRCI) is a useful and reliable tool for calculating the complexity of the pharmacotherapeutic regimen (CPR). Furthermore, a high MRCI is associated with lower adherence. However, the MRCI of opioid-dependent patients (ODP) has not been studied. The aim of this study is to calculate the Methadone Maintenance Program (MMP) persistence and the MRCI score in a ODP cohort. Second, to analyze its relationship and association with other variables. To accomplish this research, an observational study including adults with a confirmed diagnosis of opiate-dependency according to the DSM-5 in a MMP center was carried out. To define MMP-persistence, a group was created by the researchers who defined five weighted items according to their agreed importance. Our first contribution was to create a new definition of MMP-persistence. This study also identified age, comorbidities, and received methadone maintenance doses as successful predictors for MMP-persistence. We have also shown that the MRCI does not seem to be a useful tool to determine MMP-persistence, probably because there are multiple factors that influence it in addition to the CPR. It is necessary to continue searching for more precise selection and stratification tools for ODP to improve their persistence
Impaired high-density lipoprotein function and endothelial barrier stability in severe anaphylaxis.
No full text20.500.12530/87892Growing evidence demonstrates the importance of high- and low-density lipoprotein cholesterol in certain immune and allergy-mediated diseases. This study aimed to evaluate levels of high- and low-density lipoprotein cholesterol and apolipoproteins A1 and B in sera from a cohort of patients presenting with hypersensitivity reactions. We further assessed the function of high-density lipoprotein particles as well as their involvement in the molecular mechanisms of anaphylaxis. Lipid profile determination was performed in paired (acute and baseline) serum samples from 153 patients. Thirty-eight experienced a non-anaphylactic reaction and 115 had an anaphylactic reaction (88 moderate and 27 severe). Lecithin cholesterol acyl transferase activity was assessed in patient sera, and we also evaluated macrophage cholesterol efflux in response to the serum samples. Last, the effect of anaphylactic-derived high-density lipoprotein (HDL) particles on the endothelial barrier was studied. Detailed methods are provided in the Methods section in this article's Online Repository available at www.jacionline.org. Serum samples from severe anaphylactic reactions show statistically significant low levels of HDL cholesterol, low-density lipoprotein cholesterol, and apolipoproteins A1 and B, which points to their possible role as biomarkers. Specifically, HDL particles play a protective role in cardiovascular diseases. Using functional human serum cell assays, we observed impaired capacity of apolipoprotein B-depleted serum to induce macrophage cholesterol efflux in severe anaphylactic reactions. In addition, purified HDL particles from human anaphylactic sera failed to stabilize and maintain the endothelial barrier. These results encourage further research on HDL functions in severe anaphylaxis, which may lead to new diagnostic and therapeutic strategies
Infective endocarditis in HIV-infected patients. Analysis of a national cohort.
No full text20.500.12530/87858There is limited recent evidence about infective endocarditis (IE) in HIV-infected patients. Our aim was to compare IE according to HIV infection presence. Consecutive inclusion of IE patients at 46 Spanish hospitals between 2008 and 2021. From 5667 patients, 99 were HIV-infected (1·7%; 50 intravenous drugs users). Compared to patients without HIV, HIV-infected patients were more frequently male (84% vs. 67%), had younger median age (46 vs. 69 years), and less comorbidities, except liver disease (52% vs. 9%) and intravenous drug use (51% vs. 1%). They had more common tricuspid location (36% vs. 5%) and community-acquired IE (82% vs. 63%), vascular (29% vs. 17%) and cutaneous (22% vs. 7%) foci of infection, and Staphylococcus aureus aetiology (46% vs. 22%). Vegetations (84% vs. 72%), vascular phenomena (17% vs. 9%), splenomegaly (30% vs. 11%), and embolisation (41% vs 21%) were also more common. Surgical indication and surgery were less frequent in HIV-infected patients (54% vs 67%, 28% vs 47%, respectively). Median CD4 count in HIV-infected patients was 318 cells/mm3. In-hospital mortality (23% vs. 26%) and one-year mortality (25% vs. 32%) were similar in both groups. HIV infection was not independently associated with in-hospital (odds ratio 1·1, 95% CI 0·6-1·9) nor one-year mortality (hazard ratio 0·8, 95% CI 0·4-1·3). In the combined antiretroviral therapy era, less than 2% of IE patients have HIV infection. HIV-infected patients have a different clinical profile than those without HIV, but the presence of HIV does not seem to impact on IE prognosis
Transatlantic analysis of patient profiles and mid-term survival after isolated coronary artery bypass grafting: a head-to-head comparison between the European DuraGraft Registry and the US STS Registry.
No full text20.500.12530/87858Although cardiovascular surgery societies in Europe and the USA constantly strive for the exchange of knowledge and best practices in coronary artery bypass grafting (CABG), the available evidence on whether such efforts result in similar patient outcomes is limited. Therefore, in the present analysis, we sought to compare patient profiles and overall survival outcomes for up to 3 years between large European and US patient cohorts who underwent isolated CABG. Patients from the European DuraGraft Registry (n = 2,522) who underwent isolated CABG at 45 sites in eight different European countries between 2016 and 2019 were compared to randomly selected patients from the US STS database who were operated during the same period (n = 294,725). Free conduits (venous and arterial grafts) from the DuraGraft Registry patients were intraoperatively stored in DuraGraft, an endothelial damage inhibitor, before anastomosis, whereas grafts from the STS Registry patients in standard-of-care solutions (e.g., saline). Propensity score matching (PSM) models were used to account for differences in patient baseline and surgical characteristics, using a primary PSM with 35 variables (2,400 patients matched) and a secondary PSM with 25 variables (2,522 patients matched, sensitivity analysis). The overall survival for up to 3 years after CABG was assessed as the primary endpoint. The comparison of patient profiles showed significant differences between the European and US cohorts. The European patients had more left main disease, underwent more off-pump CABG, and received more arterial grafts together with more complete arterial grafting procedures. In contrast, the US patients received more distal anastomoses with more saphenous vein grafts (SVGs) that were mainly harvested endoscopically. Such differences, however, were well balanced after PSM for the mortality comparison. Mortality comparison at 30 days, 12 months, and 24 months between the European and US patients was 2.38% vs. 1.96%, 4.32% vs. 4.79%, and 5.38% vs. 6.96%, respectively. At 36 months, the mortality was significantly lower in the European patients than that of their US counterparts (7.37% vs. 9.65%; p-value = 0.016). The estimated hazard ratio (HR) was 1.29 (95% CI 1.05-1.59). This large-scale transatlantic comparative analysis shows that there are some significant differences in patient profiles between large cohorts of European and US patients. These differences were adjusted by using PSM for the mortality analysis. No significant difference in mortality was detected between groups through 2 years, but survival was significantly better in the European DuraGraft Registry patients at 3 years post-CABG
