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Immune mediators affect multiple biological functions of intestinal epithelial cells (IECs) and, like Paneth and Paneth-like cells, play an important role in intestinal epithelial homeostasis. IFN-γ a prototypical proinflammatory cytokine disrupts intestinal epithelial homeostasis. However, the mechanism underlying the process remains unknown. In this study, using in vivo and in vitro models we demonstrate that IFN-γ is spontaneously secreted in the small intestine. Furthermore, we observed that this cytokine stimulates mitochondrial activity, ROS production, and Paneth and Paneth-like cell secretion. Paneth and Paneth-like secretion downstream of IFN-γ, as identified here, is mTORC1 and necroptosis-dependent. Thus, our findings revealed that the pleiotropic function of IFN-γ also includes the regulation of Paneth cell function in the homeostatic gut.
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BACKGROUND AND PURPOSE: Information on Guillain-Barré syndrome (GBS) as an adverse event following immunization (AEFI) against SARS-CoV-2 remains scarce. We aimed to report GBS incidence as an AEFI among adult (≥18 years) recipients of 81,842,426 doses of seven anti-SARS-CoV-2 vaccines between December 24, 2020, and October 29, 2021, in Mexico. METHODS: Cases were retrospectively collected through passive epidemiological surveillance. The overall observed incidence was calculated according to the total number of administered doses. Vaccines were analyzed individually and by vector as mRNA-based (mRNA-1273 and BNT162b2), adenovirus-vectored (ChAdOx1 nCov-19, rAd26-rAd5, Ad5-nCoV, and Ad26.COV2-S), and inactivated whole-virion-vectored (CoronaVac) vaccines. RESULTS: We identified 97 patients (52 males [53.6%]; median [interquartile range] age 44 [33-60] years), for an overall observed incidence of 1.19/1,000,000 doses (95% confidence interval [CI] 0.97-1.45), with incidence higher among Ad26.COV2-S (3.86/1,000,000 doses, 95% CI 1.50-9.93) and BNT162b2 recipients (1.92/1,00,000 doses, 95% CI 1.36-2.71). The interval (interquartile range) from vaccination to GBS symptom onset was 10 (3-17) days. Preceding diarrhea was reported in 21 patients (21.6%) and mild COVID-19 in four more (4.1%). Only 18 patients were tested for Campylobacter jejuni (positive in 16 [88.9%]). Electrophysiological examinations were performed in 76 patients (78.4%; axonal in 46 [60.5%] and demyelinating in 25 [32.8%]); variants were similar across the platforms. On admission, 91.8% had a GBS disability score ≥3. Seventy-five patients (77.3%) received intravenous immunoglobulin, received seven plasma exchange (7.2%), and 15 (15.5%) were treated conservatively. Ten patients (10.3%) died, and 79.1% of survivors were unable to walk independently. CONCLUSIONS: Guillain-Barré syndrome was an extremely infrequent AEFI against SARS-CoV-2. The protection provided by these vaccines outweighs the risk of developing GBS.
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Vacina BNT162 , COVID-19 , ChAdOx1 nCoV-19 , Síndrome de Guillain-Barré , Adulto , Humanos , Masculino , Vacina BNT162/efeitos adversos , ChAdOx1 nCoV-19/efeitos adversos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Síndrome de Guillain-Barré/induzido quimicamente , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/epidemiologia , Imunoglobulinas Intravenosas/uso terapêutico , Incidência , Sistema de Registros , Estudos Retrospectivos , SARS-CoV-2 , Vacinação/efeitos adversos , Feminino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: The antiphospholipid syndrome (APS) is an autoimmune disease associated with thrombotic and non-thrombotic neurologic manifestations. APS is classified as primary (PAPS) or secondary (SAPS) when it co-exists with another autoimmune disease. We aim to describe the spectrum of acute cerebrovascular disease among patients with APS, their differences between stroke subtypes, and long-term functional outcomes. METHODS: Retrospective cohort study including adult (≥18 years) patients with APS followed in the stroke clinic of a tertiary-care reference center for autoimmune diseases in Mexico from 2009 to 2019. RESULTS: We studied 120 cases; 99 (82.5%) women; median age 43 years (interquartile range 35-52); 63.3% with SAPS. Demographics, comorbidities, and antiphospholipid antibodies (aPL) positivity were similar between APS type and stroke subtypes. Amongst index events, we observed 84 (70%) acute ischemic strokes (AIS), 19 (15.8%) cerebral venous thromboses (CVT), 11 (9.2%) intracerebral hemorrhages (ICH), and six (5%) subarachnoid hemorrhages (SAH). Sixty-seven (55.8%) were known patients with APS; the median time from APS diagnosis to index stroke was 46 months (interquartile range 12-96); 64.7% of intracranial hemorrhages (ICH or SAH) occurred ≥4 years after APS was diagnosed (23.5% anticoagulation-related); 63.2% of CVT cases developed before APS was diagnosed or simultaneously. Recurrences occurred in 26 (22.8%) patients, AIS, in 18 (69.2%); intracranial hemorrhage, in eight (30.8%). Long-term functional outcomes were good (modified Rankin Scale ≤2) in 63.2% of cases, during follow-up, the all-cause mortality rate was 19.2%. CONCLUSION: We found no differences between stroke subtypes and APS types. aPL profiles were not associated with any of the acute cerebrovascular diseases described in this cohort. CVT may be an initial thrombotic manifestation of APS with low mortality and good long-term functional outcome.
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Síndrome Antifosfolipídica , Doenças Autoimunes , Lúpus Eritematoso Sistêmico , Acidente Vascular Cerebral , Hemorragia Subaracnóidea , Trombose , Adulto , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/epidemiologia , Hemorragia Cerebral/patologia , Feminino , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Trombose/epidemiologia , Trombose/etiologiaRESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) is a systemic disease that can rapidly progress into acute respiratory failure and death. Timely identification of these patients is crucial for a proper administration of health-care resources. OBJECTIVE: To develop a predictive score that estimates the risk of invasive mechanical ventilation (IMV) among patients with COVID-19. STUDY DESIGN: Retrospective cohort study of 401 COVID-19 patients diagnosed from March 12, to August 10, 2020. The score development cohort comprised 211 patients (52.62% of total sample) whereas the validation cohort included 190 patients (47.38% of total sample). We divided participants according to the need of invasive mechanical ventilation (IMV) and looked for potential predictive variables. RESULTS: We developed two predictive scores, one based on Interleukin-6 (IL-6) and the other one on the Neutrophil/Lymphocyte ratio (NLR), using the following variables: respiratory rate, SpO2/FiO2 ratio and lactic dehydrogenase (LDH). The area under the curve (AUC) in the development cohort was 0.877 (0.823-0.931) using the NLR based score and 0.891 (0.843-0.939) using the IL-6 based score. When compared with other similar scores developed for the prediction of adverse outcomes in COVID-19, the COVID-IRS scores proved to be superior in the prediction of IMV. CONCLUSION: The COVID-IRS scores accurately predict the need for mechanical ventilation in COVID-19 patients using readily available variables taken upon admission. More studies testing the applicability of COVID-IRS in other centers and populations, as well as its performance as a triage tool for COVID-19 patients are needed.
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COVID-19/terapia , Hospitalização , Intubação , Respiração Artificial , Adulto , Idoso , Biomarcadores/metabolismo , COVID-19/epidemiologia , Feminino , Humanos , Interleucina-6/metabolismo , Masculino , México , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Neutrófilos/patologia , Taxa Respiratória , Estudos Retrospectivos , Medição de Risco , TriagemRESUMO
OBJECTIVE: Cyclophosphamide (CYC) is an alkylating agent with immunosuppressive effect by inhibiting DNA synthesis and producing apoptosis used in many autoimmune diseases, including multiple sclerosis (MS). Here, we analyze the efficacy of CYC treatment in relapsing-remitting (RRMS) and active secondary progressive MS (SPMS) in our center with a monthly scheme. METHODS: Patients with MS treated with CYC and a follow up of at least 36 months were eligible for inclusion. All participants had received a standard CYC regimen. The EDSS score mean annualized relapse rate (ARR) and progression index (PI) were measured as efficacy outcomes at 12, 24, and 36 months. Outcomes were also analyzed comparing disease course and activity. RESULTS: A total of 16 patients were included (50% male, 18.75% RRMS and 81.25% SPMS). EDSS remained stable along the follow-up period, with 62.5% improving or maintaining the same EDSS score at 12 months. PI decreased 14% and 21% at 12 and 24-36 months of follow-up, respectively. ARR decreased 20% after 12 months, 19% after 24 months, and 30.23% after 36 months. Median differences in ARR were higher in patients with high relapse activity (0.60 vs 0.07, p = 0.001) and malignant course (0.60 vs 0.17, p = 0.027). PI also differed with higher mean differences in patients with high relapse activity (0.70 vs 0.03, p = 0.016) and malignant course (1.17 vs 0.03, p = 0.003). CONCLUSIONS: CYC continues to be a valid therapeutic option, especially in regions with limited access to high-efficiency therapies particularly in patients with high relapsing activity and malignant course.
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Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Masculino , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , RecidivaRESUMO
Alcoholic liver disease (ALD) may be attributed to multiple hits driving several alterations. The aim of this work was to determine whether nucleoredoxin (NXN) interacts with flightless-I (FLII)/actin complex and how this ternary complex is altered during ALD progression induced by different ALD models. ALD was recapitulated in C57BL/6J female mice by the well-known ALD Lieber-DeCarli model, and by an in vitro human co-culture system overexpressing NXN. The effects of ethanol and low doses of lipopolysaccharides (LPS) and diethylnitrosamine (DEN) were also evaluated in vivo as a first approach of an ALD multi-hit protocol. We demonstrated that NXN interacts with FLII/actin complex. This complex was differentially altered in ALD in vivo and in vitro, and NXN overexpression partially reverted this alteration. We also showed that ethanol, LPS and DEN synergistically induced liver structural disarrangement, steatosis and inflammatory infiltration accompanied by increased levels of proliferation (Ki67), ethanol metabolism (CYP2E1), hepatocarcinogenesis (GSTP1) and LPS-inducible (MYD88 and TLR4) markers. In summary, we provide evidence showing that NXN/FLII/actin complex is involved in ALD progression and that NXN might be involved in the regulation of FLII/actin-dependent cellular functions. Moreover, we present a promising first approach of a multi-hit protocol to better recapitulate ALD pathogenesis.
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Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/patologia , Proteínas dos Microfilamentos/metabolismo , Oxirredutases/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Citocromo P-450 CYP2E1/metabolismo , Dietilnitrosamina/farmacologia , Etanol , Feminino , Lipopolissacarídeos/farmacologia , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos C57BLRESUMO
La arteritis actínica es la lesión producida a las arterias por la exposición a radiaciones ionizantes utilizadas previamente para el tratamiento radioterápico por diagnóstico de una neoplasia maligna y se presenta tras años de la exposición. Presentamos el caso de una paciente con antecedentes de Cáncer del canal anal con exposición a radioterapia en zona pélvica 21 años atrás que presento síntomas 8 años antes con signos de isquemia progresiva recibiendo tratamiento médico hasta llegar a isquemia critica en el miembro inferior izquierdo 7 meses antes con dolor en reposo y presentar lesión en hallux izquierdo 15 días antes de su internación, por lo que tras el fallo del tratamiento médico se optó por la revascularización con la realización de un By Pass extra anatómico.
Actinic arteritis is the lesion produced in the arteries by exposure to ionizing radiation previously used for radiotherapy treatment by diagnosis of a malignant neoplasm and occurs after years of exposure. We present the case of a patient with a history of anal canal cancer with exposure to pelvic radiotherapy 21 years ago who presented symptoms 8 years earlier with signs of progressive ischemia receiving medical treatment until critical ischemia in the left lower limb 7 months before With pain at rest and present lesion in the left hallux 15 days before their hospitalization, so that after the failure of the medical treatment was revascularization with the realization of an extra anatomical By Pass.
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Feminino , Humanos , Idoso , Arteriopatias Oclusivas/diagnóstico , Arteriopatias Oclusivas/cirurgia , Neoplasias , RadioterapiaRESUMO
La hemorragia digestiva alta constituye una de lasemergencias médicas más frecuentes. Es motivo de hospitalizaciónsiempre, y a pesar de los avances terapéuticosactuales, la mortalidad de los episodios agudos siguesiendo considerableSe realizó un estudio observacional, descriptivo, retrospectivo,de corte transverso en la Primera Cátedra deClínica Quirúrgica del Hospital de Clínicas de Asuncióndesde enero 2011 a diciembre 2011. Fueron evaluados 27pacientes con diagnóstico de hemorragia digestiva alta,sometidos a endoscopía digestiva alta, con el objetivo deenumerar las causas, determinar la frecuencia de resangradoy de tratamiento quirúrgico encontradas en el servicio.Se han encontrado como causas más frecuentes dehemorragia digestiva alta a la úlcera gástrica 12 casos(44%) y úlcera duodenal 10 casos (37%), habiendo concomitanciade lesiones. Tres casos (11%) requirieron unasegunda endoscopía por resangrado. En ningún caso senecesitó de una terapéutica quirúrgica para detener el sangrado
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Endoscopia do Sistema Digestório , Úlcera GástricaRESUMO
El presente documento es una recopilación de fuentes que contribuyen con el conocimiento de aspectos considerados de importancia, relacionados con las buenas prácticas del cuidado y manejo del animal de laboratorio (ratón), constituyéndose en un instrumento de referencia para el personal que trabaja en el bioterio, de producción y experimentación animal
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Animais de Laboratório/crescimento & desenvolvimento , Camundongos/crescimento & desenvolvimento , PeruRESUMO
El presente documento es una recopilación de fuentes que contribuyen con el conocimiento de aspectos considerados de importancia, relacionados con las buenas prácticas del cuidado y manejo del animal de laboratorio (ratón), constituyéndose en un instrumento de referencia para el personal que trabaja en el bioterio, de producción y experimentación animal
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Animais de Laboratório/crescimento & desenvolvimento , Camundongos/crescimento & desenvolvimento , PeruRESUMO
El autor presenta el resultado de 25 pacientes con Displejia Cerebral Espástica con 50 rodillas con deformidad en flexión. Fueron tratados con la técnica de Green & Mc Dermott. Los resultados fueron buenos en todos los casos observando en ellos mejoría tanto en el aspecto estático y dinámico; el ángulo papliteo también fue variable