Project description:Objetivo Pretendemos determinar los factores predictores de enfermedad tromboembólica pulmonar (ETEP) en pacientes con infección por SARS-CoV-2 (COVID-19) atendidos en el servicio de urgencias de un hospital terciario durante la primera ola pandémica. Métodos Estudio observacional unicéntrico realizado en una cohorte retrospectiva de pacientes con infección confirmada por SARS-CoV-2 (o alta sospecha clínico-radiológica de COVID-19) sometidos a despistaje de ETEP mediante tomografía computarizada de arterias pulmonares (TCAP). Se exploraron los factores predictores de ETEP mediante regresión logística, creándose dos modelos predictivos (sin o con los valores de dímeros-D). Resultados De un total de 274 TCAP realizados, 70 procedimientos presentaron hallazgos diagnósticos de ETEP, representando una incidencia acumulada del 25,54% (intervalo de confianza [IC] 95%: 20,49-31,14). En el modelo no ajustado por el nivel de dímeros-D, la frecuencia respiratoria > 22 rpm (odds ratio [OR]: 3,162; IC 95%: 1,627-6,148; p = 0,001) y la ausencia de hallazgos sugerentes de COVID-19 en la radiología simple de tórax (OR: 3,869; IC 95%: 0,869-17,225; p = 0,076) fueron predictores de ETEP. En el segundo modelo se mantuvo la presencia de taquipnea (OR: 4,967; IC 95%: 2,053-12,018; p < 0,001), identificándose además un nivel de dímeros-D > 3.000 ng/mL (OR: 7,494; IC 95%: 3,038-18,485; p < 0,001). Conclusiones La presencia de taquipnea (> 22 rpm) y la ausencia de hallazgos radiológicos sugestivos de infección por SARS-CoV-2 en la radiografía simple de tórax, además de los valores de dímero-D > 3.000 ng/mL, fueron identificados como factores predictores de ETEP en pacientes con COVID-19.
Project description:Introduction After the World Health Organization declared the COVID-19 outbreak a pandemic, the number of patients with confirmed SARS-CoV-2 infection (COVID-19) has increased exponentially, and gastroenterologists and other specialists most likely will be involved in the care of those patients. Aim To evaluate the knowledge Latin American gastroenterologists and endoscopists (staff physicians and residents) have about the characteristics of COVID-19, as well as the prevention measures to be taken during endoscopic procedures. Materials and methods We conducted a cross-sectional study that included gastroenterologists and endoscopists from 9 Latin American countries. An electronic questionnaire was applied that was designed to evaluate the knowledge of symptoms, risk groups for severe disease, prevention measures, and the reprocessing of endoscopes utilized in patients with COVID-19. Results Information was obtained from 133 physicians. Ninety-five percent of them correctly identified the most frequent symptoms of the virus, and 60% identified the 3 risk groups for severe disease. Sixty-six percent of those surveyed did not consider it necessary to use standard precautions during endoscopic procedures, and 30% did not consider contact precautions necessary. Forty-eight percent of the participants surveyed were not familiar with the protocol for reprocessing the endoscopes utilized in patients with COVID-19. Conclusion The majority of the gastroenterologists and endoscopists surveyed were familiar with the signs and symptoms of COVID-19 and the populations at risk for complications. There was a lack of knowledge about prevention measures (during clinical care and endoscopic procedures) and the reprocessing of endoscopic equipment by 70% and 48%, respectively, of those surveyed. Dissemination and teaching strategies that increase the knowledge of specific biosafety measures must be carried out.
Project description:ObjectiveTo describe the clinical features and outcome of anti-NMDA receptor (NMDAR) encephalitis in patients ?45 years old.MethodObservational cohort study.ResultsIn a cohort of 661 patients with anti-NMDAR encephalitis, we identified 31 patients ?45 years old. Compared with younger adults (18-44 years), older patients were more often male (45% vs. 12%, p < 0.0001), had lower frequency of tumors (23% vs. 51%, p = 0.002; rarely teratomas), had longer median time to diagnosis (8 vs 4 weeks, p = 0.009) and treatment (7 vs. 4 weeks, p = 0.039), and had less favorable outcome (modified Rankin Scale score 0-2 at 2 years, 60% vs. 80%, p < 0.026). In multivariable analysis, younger age (odds ratio [OR] 0.15, confidence interval [CI] 0.05-0.39, p = 0.0001), early treatment (OR 0.60, CI 0.47-0.78, p < 0.0001), no need for intensive care (OR 0.09, CI 0.04-0.22, p < 0.0001), and longer follow-up (p < 0.0001) were associated with good outcome. Rituximab and cyclophosphamide were effective when first-line immunotherapies failed (OR 2.93, CI 1.10-7.76, p = 0.031). Overall, 60% of patients older than 45 years had full or substantial recovery at 24 months follow-up.ConclusionsAnti-NMDAR encephalitis is less severe in patients ?45 years old than in young adults, but the outcome is poorer in older patients. In this age group, delays in diagnosis and treatment are more frequent than in younger patients. The frequency of underlying tumors is low, but if present they are usually carcinomas instead of teratomas in younger patients. Early and aggressive immunotherapy will likely improve the clinical outcome.
Project description:Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis is an acute autoimmune neurological disorder. The cause of this disease is often unknown, and previous studies revealed that it might be caused by a virus, vaccine or tumor. It occurs more often in females than in males. Several cases were reported to be related to vaccination such as the H1N1 vaccine and tetanus/diphtheria/pertussis and polio vaccines. In this study, we reported an anti-NMDA receptor encephalitis case that may be caused by Japanese encephalitis vaccination. To investigate the association between anti-NMDA receptor encephalitis and vaccination, we analyzed the phylogenetic relationship of the microRNAs, which significantly regulate these vaccine viruses or bacteria, and the phylogenetic relationship of these viruses and bacteria. This reveals that anti-NMDA receptor encephalitis may be caused by Japanese encephalitis vaccination, as well as H1N1 vaccination or tetanus/diphtheria/pertussis and polio vaccinations, from the phylogenetic viewpoint.
Project description:Introducción en 2019 surgió el SARS-CoV-2, causante de la pandemia por la COVID-19 que se extendió rápidamente alrededor del mundo; en casos graves, este puede desencadenar un síndrome de tormenta de citoquinas y conllevar a la muerte. Las manifestaciones cutáneas pueden asociarse a la expresión del receptor ACE2 en queratinocitos, estas se han descrito en la literatura de diversos países. La presente revisión busca documentar las presentaciones cutáneas que se han descrito en los pacientes con COVID-19 en América Latina. Metodología realizamos una búsqueda en 9 bases de datos de artículos en español, portugués e inglés, hasta el 10 de marzo del 2021, utilizando los términos: «Skin», «Cutaneous manifestations», «COVID 19», «SARS-CoV-2», asociándolos al nombre de los países latinoamericanos. Se obtuvieron los datos básicos de los pacientes incluidos, luego se creó una tabla en Microsoft Excel para analizar y comparar los datos. Resultados se identificaron 22 publicaciones de 9 países. Obtuvimos información de 92 pacientes, predominantemente de sexo femenino y edad promedio de 31,6 años. Fueron documentadas 99 lesiones dermatológicas, en orden de frecuencia correspondieron a erupciones cutáneas, habones, petequias-púrpura y pápulas. En 70 pacientes se describió el segmento corporal afectado, principalmente el tronco, los miembros inferiores y superiores. Encontramos 39 fotografías y 5 histopatologías. Los tratamientos más comunes fueron los corticoides, los antipalúdicos y el interferón recombinante. Conclusiones se observan diferencias en las manifestaciones cutáneas por la COVID-19, entre las publicaciones latinoamericanas en comparación a los demás países. Parece haber un patrón propio, donde predomina la erupción cutánea eritematosa con habones, mientras que la pseudo-perniosis fue menos representativa.
Project description:Dysregulated immune responses contribute to the excessive and uncontrolled inflammation observed in severe COVID-19. However, how immunity to SARS-CoV-2 is induced and regulated remains unclear. Here we uncover a role of the complement system in the induction of innate and adaptive immunity to SARS-CoV-2. Complement rapidly opsonizes SARS-CoV-2 particles via the lectin pathway. Complement-opsonized SARS-CoV-2 efficiently induces type-I interferon and pro-inflammatory cytokine responses via activation of dendritic cells, which are inhibited by antibodies against the complement receptors (CR) 3 and 4. Serum from COVID-19 patients, or monoclonal antibodies against SARS-CoV-2, attenuate innate and adaptive immunity induced by complement-opsonized SARS-CoV-2. Blocking of CD32, the FcγRII antibody receptor of dendritic cells, restores complement-induced immunity. These results suggest that opsonization of SARS-CoV-2 by complement is involved in the induction of innate and adaptive immunity to SARS-CoV-2 in the acute phase of infection. Subsequent antibody responses limit inflammation and restore immune homeostasis. These findings suggest that dysregulation of the complement system and FcγRII signaling may contribute to severe COVID-19.
Project description:We recently described a severe, potentially lethal, but treatment-responsive encephalitis that associates with autoantibodies to the NMDA receptor (NMDAR) and results in behavioral symptoms similar to those obtained with models of genetic or pharmacologic attenuation of NMDAR function. Here, we demonstrate that patients' NMDAR antibodies cause a selective and reversible decrease in NMDAR surface density and synaptic localization that correlates with patients' antibody titers. The mechanism of this decrease is selective antibody-mediated capping and internalization of surface NMDARs, as Fab fragments prepared from patients' antibodies did not decrease surface receptor density, but subsequent cross-linking with anti-Fab antibodies recapitulated the decrease caused by intact patient NMDAR antibodies. Moreover, whole-cell patch-clamp recordings of miniature EPSCs in cultured rat hippocampal neurons showed that patients' antibodies specifically decreased synaptic NMDAR-mediated currents, without affecting AMPA receptor-mediated currents. In contrast to these profound effects on NMDARs, patients' antibodies did not alter the localization or expression of other glutamate receptors or synaptic proteins, number of synapses, dendritic spines, dendritic complexity, or cell survival. In addition, NMDAR density was dramatically reduced in the hippocampus of female Lewis rats infused with patients' antibodies, similar to the decrease observed in the hippocampus of autopsied patients. These studies establish the cellular mechanisms through which antibodies of patients with anti-NMDAR encephalitis cause a specific, titer-dependent, and reversible loss of NMDARs. The loss of this subtype of glutamate receptors eliminates NMDAR-mediated synaptic function, resulting in the learning, memory, and other behavioral deficits observed in patients with anti-NMDAR encephalitis.
Project description:BACKGROUND:Clinical brain MRI is normal in the majority of patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. However, extensive deep white matter damage wasrecently identifiedin these patients using diffusion weighted imaging. Here, our aim was to study a particularly vulnerable brain compartment, the late myelinating superficial white matter. METHODS:Forty-six patients with anti-NMDAR encephalitis were included. Ten out of these were considered neurologically recovered (modified Rankin scale of zero), while 36 patients were non-recovered. In addition, 30 healthy controls were studied. MRI data were collected from all subjects and superficial white matter mean diffusivity derived from diffusion tensor imaging was compared between groups in whole brain, lobar and vertex-based analyses. Patients underwent comprehensive cognitive testing, and correlation analyses were performed between cognitive performance and superficial white matter integrity. RESULTS:Non-recovered patients showed widespread superficial white matter damage in comparison to recovered patients and healthy controls. Vertex-based analyses revealed that damage predominated in frontal and temporal lobes. In contrast, the superficial white matter was intact in recovered patients. Importantly, persistent cognitive impairments in working memory, verbal memory, visuospatial memory and attention significantly correlated with damage of the superficial white matter in patients. CONCLUSIONS:Anti-NMDAR encephalitis is associated with extensive superficial white matter damage in patients with incomplete recovery. The strong association with impairment in several cognitive domains highlights the clinical relevance of white matter damage in this disorder and warrants investigations of the underlying pathophysiological mechanisms.
Project description:To evaluate the therapeutic potential of bortezomib, a proteasome inhibitor that target plasma cells, in order to revive stalled recovery in patients with anti-N-methyl-d-aspartate (NMDA) receptor encephalitis who remain bedridden even after aggressive immunotherapy.We consecutively enrolled patients with anti-NMDA receptor encephalitis who remained bedridden after first-line immunotherapy (steroids and intravenous immunoglobulin), second-line immunotherapy (rituximab), and tocilizumab treatment, and treated them with subcutaneous bortezomib. Clinical response, functional recovery, and changes in antibody titer in the serum and cerebrospinal fluid were measured.Before the bortezomib treatment, the five patients with severe refractory anti-NMDA receptor encephalitis were in a vegetative state. During the 8 months of follow-up period, three patients improved to minimally conscious states within 2 months of bortezomib treatment, one failed to improve from a vegetative state. However, no patient achieved functional recovery as measured by the modified Rankin Scale score (mRS). Three patients advanced to a cyclophosphamide with bortezomib and dexamethasone regimen, which only resulted in additional adverse events, without mRS improvement. Among the four patients whose antibody titer was followed, two demonstrated a twofold decrease in the antibody titer in serum and/or cerebrospinal fluid after 2 cycles of bortezomib.Although there were some improvements in severe refractory patients, clinical response to bortezomib was limited and not clearly distinguishable from the natural course of the disease. The clinical benefit of bortezomib in recent studies requires further validation in different clinical settings.