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Although B cells and B cell activating factor (BAFF) have been previously implicated in MS pathogenesis, data regarding the genetic influence of BAFF polymorphisms on MS susceptibility are limited. Here we aim to explore whether BAFF polymorphisms could contribute to MS susceptibility. 156 RRMS patients fulfilling the revised McDonald criteria for MS diagnosis and 220 HCs were enrolled. Clinical, laboratory, and imaging characteristics were recorded. BAFF rs9514827, rs1041569, and rs9514828 polymorphisms were assessed by RFLP-PCR in DNA samples extracted from whole peripheral blood. The BAFF rs1041569 TT genotype along with the CTT and TTC haplotypes were associated with significantly increased risk for MS development in female MS patients compared to healthy female counterparts. These findings were not confirmed in males. The rs1041569 BAFF variant together with the CTT and TTC BAFF haplotypes derived from the BAFF rs9514827, rs1041569, and rs9514828 polymorphisms may represent novel genetic contributors to the development of MS in females.
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Predisposición Genética a la Enfermedad , Esclerosis Múltiple , Femenino , Humanos , Masculino , Factor Activador de Células B/genética , Frecuencia de los Genes , Genotipo , Esclerosis Múltiple/genética , Polimorfismo de Nucleótido SimpleRESUMEN
PURPOSE: The aim of the study was to evaluate extraocular muscle (EOM) atrophy and fatty replacement in ocular myasthenia gravis (OMG) and generalized myasthenia gravis (GMG) patients with chronic and untreated ocular symptoms or with inadequate response to immunotherapy and unprovoked ocular exacerbations despite chronic immunotherapy. METHODS: Nineteen patients with either OMG or GMG and 19 healthy age-matched controls underwent an orbital MRI. Visually obvious muscle atrophy and muscle fatty replacement were evaluated by two raters independently. Maximum thickness of EOM was measured. Measurements of the muscles of each participant were added up, in order to calculate the total thickness. RESULTS: Eleven patients suffered from AChR-positive GMG, and 8 patients from OMG. All patients had chronic ocular symptoms or inadequate response to corticosteroids and unprovoked ocular exacerbations in spite of immunotherapy. Fatty replacement was reported in 6/19 (31.6%) patients and 0/19 (0%) controls (p = 0.02). Obvious atrophy in at least one muscle was reported in 8/19 (42.1%) patients and 1/19 (5.3%) controls (p = 0.019). Statistically significant differences between the two groups were also found in the mean total thickness, as well as in the thickness of superior recti, levator palpebrae, inferior recti, and superior oblique muscles. CONCLUSION: EOM atrophy and fatty replacement were seen frequently in our series of MG patients with treatment difficulties and frequent relapses of ocular involvement.
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Miastenia Gravis , Músculos Oculomotores , Atrofia , Humanos , Imagen por Resonancia Magnética , Miastenia Gravis/diagnóstico por imagen , Miastenia Gravis/terapia , Recurrencia Local de Neoplasia , Músculos Oculomotores/diagnóstico por imagenRESUMEN
Glucocerebrosidase gene (GBA) mutations are the most common genetic contributor to Parkinson's disease (PD) and are associated with decreased glucocerebrosidase (GCase) enzymatic activity in PD. PD patients without GBA mutations also exhibit lower levels of GCase activity in the central nervous system suggesting a potential contribution of the enzyme activity in disease pathogenesis, possibly by alteration of lysosomal function. α-synuclein (ASYN), a protein with a central role in PD pathogenesis, has been shown to be secreted partly in association with exosomes. It is possible that a dysfunction of the endocytic pathway through GCase may result in altered exosome release of ASYN. The aim of this study was to examine whether manipulating GCase activity in vivo and in vitro could affect ASYN accumulation and secretion. GCase overexpression in vitro resulted in a significant decrease of exosome secretion. Chronic inhibition of GCase activity in vivo, by administration of the covalent inhibitor conduritol-B epoxide in A53T-synuclein alpha gene Tg mice significantly elevated intracellular oligomeric ASYN species. Importantly, GCase inhibition, induced a profound increase in the number of brain exosomes released, as well as exosome-associated ASYN oligomers. Finally, virus-mediated expression of mutant GBA in the mouse striatum increased ASYN secretion in the same region. Together, these results provide for the first time evidence that a decrease of GCase or overexpression of mutant GCase in a chronic in vivo setting can affect ASYN secretion. Such effects may mediate enhanced propagation of ASYN, driving pathology in GBA-associated PD.
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Exosomas/genética , Glucosilceramidasa/genética , Enfermedad de Parkinson/genética , alfa-Sinucleína/genética , Animales , Encéfalo/metabolismo , Encéfalo/fisiopatología , Modelos Animales de Enfermedad , Exosomas/metabolismo , Glucosilceramidasa/metabolismo , Humanos , Inositol/administración & dosificación , Inositol/análogos & derivados , Lisosomas/genética , Lisosomas/metabolismo , Ratones , Mutación , Enfermedad de Parkinson/fisiopatologíaRESUMEN
BACKGROUND: Listeria monocytogenes is an opportunistic pathogen of the central nervous system commonly associated with impaired cell-mediated immunity. We hereby present a case of adult neurolisteriosis where the only immunological feature persistently present was serum IgM deficiency, suggesting that non-specific humoral immunity may also play a central role in the control of neuroinvasion by Listeria monocytogenes. CASE PRESENTATION: A 62-year-old male who had never experienced severe infections presented with headache, nuchal rigidity and confusion. Neuroimaging was normal and lumbar puncture revealed pleiocytosis (760 leukocytes/mm3) and hypoglycorrhachia (34 mg/dL). The patient was treated empirically for bacterial meningitis. Indeed, further analysis of the CSF showed infection by Listeria monocytogenes, which was accompanied by reduced serum IgM levels that persisted well beyond the period of acute bacterial infection. Levels of IgG and IgA isotypes, along with peripheral blood counts of major leukocyte subsets, were at the same time largely preserved. Intriguingly, the absence of membrane-bound IgM on B cells was essentially complete in the acute post-infection period leading to a remarkable recovery after 12 months, suggesting that mechanisms other than defective membrane expression are underlying serum deficiency. CONCLUSIONS: As far as we know, this is the first reported case of neurolisteriosis associated with IgM deficiency in an adult individual without a history of severe infections or other underlying conditions. A possible role of circulating IgM against invasive disease caused by Listeria monocytogenes, particularly in the early course of host-pathogen interaction, is discussed.
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Huésped Inmunocomprometido , Inmunoglobulina M/deficiencia , Meningitis por Listeria/inmunología , Humanos , Síndromes de Inmunodeficiencia/complicaciones , Masculino , Persona de Mediana EdadRESUMEN
AIM: In the current review study, we present recent data regarding the importance of intertwin estimated fetal weight (EFW) and crown rump length (CRL) discordance for the prediction of adverse perinatal outcome both in monochorionic and in dichorionic diamniotic gestations. RESULTS: Twins with significant weight disparity are associated with higher rates of perinatal morbidity and mortality, regardless of gestational age at delivery. However, there is no agreement regarding as to the cut off value above which the perinatal outcome is unfavorably affected and the threshold range from 10 to 30%. On the other hand, CRL discrepancy has proved to be a weak predictor of adverse outcomes, such as fetal or neonatal death in fetuses without chromosomal and structural abnormalities. In clinical practice, decisions about obstetric surveillance of discordant twin gestations, frequency of fetal sonographic monitoring and time of delivery are usually based on amniotic fluid volume and Doppler assessments on a weekly basis. CONCLUSION: Significant EFW discordance leads to adverse perinatal outcome, although the cut-off value has not yet been estimated. CRL discrepancy is not correlated well with adverse perinatal outcome. However, increased monitoring of women with EFW and CRL discrepancy is suggested.
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Largo Cráneo-Cadera , Peso Fetal , Embarazo Gemelar , Corion/patología , Corion/fisiopatología , Enfermedades en Gemelos/diagnóstico por imagen , Enfermedades en Gemelos/etiología , Femenino , Retardo del Crecimiento Fetal/diagnóstico por imagen , Retardo del Crecimiento Fetal/etiología , Humanos , Recién Nacido , Placenta/irrigación sanguínea , Embarazo , Resultado del Embarazo , Ultrasonografía PrenatalRESUMEN
OBJECTIVE: Pre- or early-pregnancy obesity carries significant health implications. This retrospective cohort study investigates the association between pre- or early-pregnancy body mass index (BMI) and the risk of fetal and neonatal death in pregnancies implicated by obesity in a Mediterranean country. STUDY DESIGN: Data on pregnancies delivered during 2003-2008 at a University hospital was linked to data from regional registry. Logistic regression models were used to determine the odds ratios of a spontaneous fetal death and perinatal death among overweight, obese, and morbid obese women. RESULTS: Independent predictors of fetal death were maternal prepregnancy BMI over 25, maternal age, maternal co-morbidities, and maternal residence in an island. Perinatal mortality was independently correlated to neonatal birthweight, maternal age, maternal residence in towns and villages, and maternal BMI over 40. Overall, maternal residence in an island, maternal autoimmune disease, and maternal prepregnancy BMI (over 25) were independent risk factors predicting offspring death (both intrauterine and perinatal). CONCLUSIONS: Maternal obesity is correlated to offspring's mortality during fetal and/or perinatal period. This is one of the very few studies in a Mediterranean country. This study underlines the need for public health interventions to prevent obesity in young women.
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Muerte Fetal/etiología , Obesidad/complicaciones , Mortalidad Perinatal , Complicaciones del Embarazo/epidemiología , Adulto , Femenino , Grecia/epidemiología , Humanos , Embarazo , Complicaciones del Embarazo/etiología , Resultado del Embarazo , Estudios RetrospectivosRESUMEN
INTRODUCTION: Progressive multifocal leukoencephalopathy (PML) is a potentially life-threatening complication among Multiple Sclerosis (MS) patients under natalizumab treatment, with serum anti-JCV antibody titers being used for stratification risk. Given the critical role of interferon (IFN)/B-cell activating factor (BAFF) axis in humoral immune responses against viruses, we explored whether it is involved in the generation of serum anti-JCV antibodies among these patients. METHODS: 162 consecutive patients with relapsing-remitting MS under natalizumab treatment were included. Serum anti-JCV antibodies were measured at baseline, as well as 12 and 24 months after treatment initiation. Type I and II IFN-inducible genes and BAFF expression were quantitated in peripheral blood by qRT-PCR. Moreover, BAFF rs9514828, rs1041569, and rs9514827 gene variants were assessed by RFLP-PCR. RESULTS: While type I and II IFN inducible gene expression were not associated with anti-JCV serum titers, the latter were significantly correlated with BAFF gene expression. Of interest, the TTT haplotype of the studied BAFF variants was more frequently detected in male, but not female anti-JCV (+) MS patients compared to anti-JCV (-) counterparts at baseline, as well as at 12 months and 24 months of natalizumab treatment. Measures of clinical validity/utility for the BAFF TTT haplotype showed 88% specificity, 45%, positive predictive value, and sensitivity of 70% for the discrimination of anti-JCV (+) male MS patients after 24 months of treatment. CONCLUSIONS: Our study suggests an implication of the BAFF axis in the production of serum anti-JCV antibodies. Additionally, the BAFF TTT haplotype derived from the rs9514828, rs1041569, and rs9514827 variants may represent a novel risk factor for anti-JCV seropositivity and indirectly for PML development among male MS patients treated with natalizumab.
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Factor Activador de Células B , Factores Inmunológicos , Virus JC , Leucoencefalopatía Multifocal Progresiva , Natalizumab , Humanos , Natalizumab/uso terapéutico , Factor Activador de Células B/sangre , Factor Activador de Células B/genética , Masculino , Leucoencefalopatía Multifocal Progresiva/sangre , Leucoencefalopatía Multifocal Progresiva/genética , Adulto , Femenino , Factores Inmunológicos/uso terapéutico , Virus JC/inmunología , Virus JC/genética , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/sangre , Esclerosis Múltiple Recurrente-Remitente/genética , Esclerosis Múltiple Recurrente-Remitente/inmunología , Persona de Mediana Edad , Anticuerpos Antivirales/sangre , Polimorfismo de Nucleótido SimpleRESUMEN
SCLC is an aggressive cancer type with high metastatic potential and bad prognosis. CTCs are a valuable source of tumor cells in blood circulation and are among the major contributors to metastasis. In this study we evaluated the number of CTCs that express PD-L1 in treatment-naïve ES-SCLC patients receiving ICI in a front-line setting. Moreover, we explored the percentages of different immune T-cell subsets in circulation to assess their potential role in predicting responses. A total of 43 patients were enrolled-6 of them with LS-SCLC, and 37 with ES-SCLC disease. In addition, PBMCs from 10 healthy donors were used as a control group. Different T-cell subtypes were examined through multicolor FACS analysis and patients' CTCs were detected using immunofluorescence staining. SCLC patients had higher percentages of PD-1-expressing CD3+CD4+ and CD3+CD8+ T-cells, as well as elevated PD-1 protein expression compared to healthy individuals. Additionally, in ES-SCLC patients, a positive correlation between CD3+CD8+PD-1+ T-cells and PD-L1+ CTCs was detected. Importantly, patients harboring higher numbers of CD3+CD8+PD-1+ T-cells together with PD-L1+CTCs had a survival advantage when receiving front-line immunotherapy. Thus, this study proposes, for first time possible, immune cell-CTCs interaction, as well as a potential novel clinical biomarker for ICI responses in ES-SCLC patients.
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The Mediterranean Sea has been sampled irregularly by research vessels in the past, mostly by national expeditions in regional waters. To monitor the hydrographic, biogeochemical and circulation changes in the Mediterranean Sea, a systematic repeat oceanographic survey programme called Med-SHIP was recommended by the Mediterranean Science Commission (CIESM) in 2011, as part of the Global Ocean Ship-based Hydrographic Investigations Program (GO-SHIP). Med-SHIP consists of zonal and meridional surveys with different frequencies, where comprehensive physical and biogeochemical properties are measured with the highest international standards. The first zonal survey was done in 2011 and repeated in 2018. In addition, a network of meridional (and other key) hydrographic sections were designed: the first cycle of these sections was completed in 2016, with three cruises funded by the EU project EUROFLEETS2. This paper presents the physical and chemical data of the meridional and key transects in the Western and Eastern Mediterranean Sea collected during those cruises.
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Antibodies to glutamic acid decarboxylase (GAD) have been predominantly associated with stiff-person syndrome (SPS), which is often accompanied by organ-specific autoimmune diseases, such as late-onset type 1 diabetes. Autoimmune retinal pathology in SPS has recently been suggested to coexist in patients suffering from this disease; however, evidence reporting potential treatment options for the neurological and visual symptoms these patients experience remains scarce. We provide a review of the relevant literature, presenting a rare case of a middle-aged woman with autoimmune retinopathy (AIR) followed by stiff-leg syndrome who responded to intravenous immune globulin treatment (IVIg). Our report adds to previously reported data supporting the efficacy of IVIg in SPS spectrum disorders while also proposing the potential effect of IVIg in treating SPS spectrum patients with coexisting AIR.
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In the period 1987-2017, a series of physical and chemical measurements related to oxygen variability at a trough area with a maximum depth of ~420 m in the West Saronikos Gulf, reveal the following: In the early 90s, deep winter mixing occurred resulting in an oxygenation down to ~420 m followed by an oxygen decline. This decline reached near-bottom hypoxic conditions (O2 < ~62 µM (µmol/L)) after 1998, while a denitrification phase occurred after 2000 and a complete bottom anoxia in 2005. In June 2012, an oxygenation down to ~350 m was detected that most likely occurred in winter 2012. The 2012 oxygenation raised the until-then anoxic bottom concentrations to hypoxic ones in the years towards 2017 via vertical diffusive oxygen transfer. Observations of the benthic communities during the hypoxia, severe hypoxia (O2 < ~15 µM) and oxygen recovery phases showed a peak of opportunists in the hypoxia and a long faunal depletion in the severe hypoxia phases. A reversal in the benthic community structure appeared after the oxygenation of 2012 with the (re)appearance of opportunists while, in 2017, the community showed signs of retreat to earlier stages. The main anthropogenic pressure that could tentatively affect the oxygen concentration in the study area is posed by the Athens treated-sewage outfall at ~40 km away from the trough, which inputs organic matter into the Saronikos Gulf through effluent water of reduced salinity that, in addition, may alter the stratification opposing the vertical mixing. We show that the treated sewage output had no influence on a) the stratification, b) the particulate and dissolved organic carbon and c) the sewage-derived organic matter. Instead, the long-term dissolved oxygen variability with the deep renewal events was mostly driven by the large-scale atmosphere-ocean conditions (heat exchange and evaporation-minus-precipitation budget) that determine the hydrographic characteristics and the winter mixing.
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BACKGROUND: Some reports suggest that psychotic features may occur in the early stages of Parkinson's disease (PD), but sensitive tools have not been utilized. OBJECTIVE: The aim was to evaluate the presence of psychotic symptoms using detailed scales and to assess the association with clinical characteristics. METHODS: Healthy controls and patients within three years of PD onset were recruited. Participants were examined for psychotic symptoms using two different instruments: the Comprehensive Assessment of At-Risk Mental States (CAARMS) and a 10 question PD specific psychosis severity scale (10PDQ). In the PD group, medication use, motor and non-motor symptoms were documented. RESULTS: Based on CAARMS and 10PDQ scales, psychotic features were present in 39% (27/70) of patients and 4% (3/74) of controls. The prevalence of passage hallucinations and illusions was significantly higher in PD compared to the control group. The presence of PD-associated psychotic features was not significantly affected by medication, motor severity or global cognitive status. Higher prevalence of overall non-motor manifestations, REM sleep behavior disorder (RBD) and depressive symptoms was significantly associated with the manifestation of psychotic features in PD [(adjusted OR:1.3; 95% CI:1.1-1.6; pâ=â0.003), (adjusted OR:1.3; 95% CI:1.0-1.6; pâ=â0.023), and (adjusted OR:1.2; 95% CI:1.0-1.4;pâ=â0.026)]. CONCLUSIONS: Psychotic phenomena mainly of minor nature are highly common in early PD. Cumulative non-motor symptoms, RBD and depressive features are associated with the presence of psychotic symptoms in this non-demented, early-stage PD population. More studies are needed to clarify the mechanisms that contribute to the onset of psychotic features in early PD.
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Enfermedad de Parkinson , Trastornos Psicóticos , Trastorno de la Conducta del Sueño REM , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/epidemiología , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/epidemiología , Trastornos Psicóticos/etiología , Alucinaciones/diagnóstico , Alucinaciones/epidemiología , Alucinaciones/etiología , Trastorno de la Conducta del Sueño REM/diagnóstico , Trastorno de la Conducta del Sueño REM/epidemiología , Trastorno de la Conducta del Sueño REM/etiología , PrevalenciaRESUMEN
OBJECTIVES: The aim was to explore the correlations between Jumping to Conclusions (JtC) tendency and neuropsychiatric features in patients with early Parkinson's disease (PD). BACKGROUND: According to few reports, PD patients with impulsive-compulsive behaviors (ICBs) are prone to working memory difficulties including JtC bias. The correlation of psychotic features and JtC tendency remains still unclear. METHODS: Healthy controls and patients within 3 years of PD onset were recruited. Participants were examined for psychotic symptoms using a 10 question PD-specific psychosis severity scale. JtC was measured by a probalistic reasoning scenario (beads task). In PD group, medication use, motor and non-motor symptoms were documented. Impulsivity was evaluated using the Questionnaire for Impulsive-Compulsive Disorders in PD (QUIP). RESULTS: The prevalence of JtC bias was 9% (6/70) in healthy individuals, compared to 32% (22/68) of PD group [p = 0.001]. No association was detected between the presence of JtC tendency and PD-associated psychosis (p = 0.216). Patients with JtC had shorter duration of PD, more tremor-dominant PD subtype and higher QUIP scores, regardless of the dopaminergic therapy (p = 0.043, p = 0.015, p = 0.007, respectively). A trend towards attention and inhibition control deficit was noticed in JtC patients. CONCLUSIONS: We found a high prevalence of JtC bias in early, cognitively intact PD population and a potential link between subthreshold ICBs and poor performance on beads task. Additional studies are needed to confirm our results and elaborate on the mechanisms that correlate impulsivity with JtC tendency, which are likely to be different from those mediating psychotic features in early PD.
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Enfermedad de Parkinson , Trastornos Psicóticos , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/epidemiología , Trastornos Psicóticos/epidemiología , Trastornos Psicóticos/etiología , Trastornos Psicóticos/diagnóstico , Conducta Impulsiva/fisiología , Encuestas y Cuestionarios , Memoria a Corto Plazo/fisiologíaRESUMEN
BACKGROUND AND AIM: Cancer cachexia is a metabolic syndrome related with poor outcome. Cytokines play a key role in the pathophysiology of that syndrome. The aim of this study was to investigate the potential correlations between nutritional status, systemic inflammation, and psychological distress in cancer patients. The prognostic significance of the recorded parameters was also assessed. PATIENTS AND METHODS: Patients with metastatic lung cancer were eligible. Mini Nutritional Assessment (MNA) was used for the evaluation of nutritional status, Glasgow Prognostic Score (GPS) for the estimation of systemic inflammation, and Hospital Anxiety and Depression Scale (HADS) for psychological assessment. RESULTS: Totally, 122 patients were enrolled (71.3% with NSCLC and 28.7% with SCLC). The following correlations were observed: MNA and GPS (r = 0.289, p = 0.001), MNA and HADS (depression scale) (r = 0.275, p = 0.002), GPS and HADS (depression scale) (r = 0.256, p = 0.004), and GPS and HADS (anxiety scale) (r =0.194, p =0.033). In univariate analysis, GPS (p = 0.002) and MNA (p = 0.010) emerged as significant predictors of survival. In multivariate analysis, both MNA (p = 0.032) and GPS (p = 0.020) retained their importance. CONCLUSIONS: This study highlights the associations between nutritional status, systemic inflammation, and psychological distress, supporting their common underlying pathophysiological mechanisms and further suggesting the necessity of a holistic anti-cachectic approach.
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Reacción de Fase Aguda/etiología , Depresión/etiología , Neoplasias Pulmonares/psicología , Estado Nutricional , Adulto , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/metabolismo , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Medición de Riesgo , Albúmina Sérica/análisis , Encuestas y CuestionariosRESUMEN
The aim of this study was to evaluate indices of respiratory failure in terms of their ability to predict respiratory impairment and need for ventilatory support in late-preterm neonates with respiratory distress. Arterial blood gas data during the first 12 postnatal hours or until intubation were recorded in 155 neonates with gestational age 34(0/7)-36(6/7) weeks admitted in the NICU with respiratory distress between January 2006 and June 2008. Alveolar-arterial oxygen tension difference (A-aDO(2)), arterial to alveolar oxygen tension ratio (a/A ratio), and partial arterial oxygen tension to inspired oxygen fraction ratio (PaO(2)/FiO(2)) were calculated. Considering the worst single value of each parameter, receiver operating characteristic curve analyses and area under the curve (AUC) comparisons were used to evaluate their predictive performance. Fifty-five neonates (35.5%) required mechanical ventilation. The predictive performances of the maximum A-aDO(2) (AUC 0.97), minimum a/A ratio (AUC 0.95), and minimum PaO(2)/FiO(2) (AUC 0.95) were similar. The A-aDO(2) at a threshold of >200 mmHg proved to be more effective than the other parameters, having excellent positive and negative likelihood ratios of 24.5 and 0.02, respectively. This threshold was achieved by 98.25% of the neonates who developed respiratory failure at a median of 3 h before the ventilatory support to be definitely decided. Composite indices, such as A-aDO(2), a/A ratio, and PaO(2)/FiO(2), can reasonably predict respiratory failure in late-preterm neonates with respiratory distress, allowing for closer monitoring, early medical intervention, or transfer to a level III neonatal unit.
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Oxígeno/sangre , Alveolos Pulmonares/metabolismo , Intercambio Gaseoso Pulmonar , Síndrome de Dificultad Respiratoria del Recién Nacido/sangre , Insuficiencia Respiratoria/sangre , Insuficiencia Respiratoria/diagnóstico , Análisis de los Gases de la Sangre , Femenino , Edad Gestacional , Humanos , Recién Nacido , Recien Nacido Prematuro , Unidades de Cuidado Intensivo Neonatal , Masculino , Terapia por Inhalación de Oxígeno , Valor Predictivo de las Pruebas , Embarazo , Tercer Trimestre del Embarazo , Alveolos Pulmonares/irrigación sanguínea , Respiración Artificial , Síndrome de Dificultad Respiratoria del Recién Nacido/complicaciones , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/prevención & controlRESUMEN
INTRODUCTION: Accumulating data highlights that the dysregulation of type I interferon (IFN) pathways plays a central role in the pathogenesis of several systemic and organ-specific autoimmune diseases. Advances in understanding the role of type I IFNs in these disorders can lead to targeted drug development as well as establishing potential disease biomarkers. AREAS COVERED: Here, we summarize current knowledge regarding the role of type I IFNs in the major systemic, as well as organ-specific, autoimmune disorders, including prominent inflammatory CNS disorders like multiple sclerosis. EXPERT OPINION: Type I IFN involvement and its clinical associations in a wide spectrum of autoimmune diseases represents a promising area for research aiming to unveil common pathogenetic pathways in systemic and organ-specific autoimmunity.
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Enfermedades Autoinmunes , Interferón Tipo I , Enfermedades Autoinmunes/diagnóstico , Autoinmunidad , Humanos , Inmunoterapia , Interferón Tipo I/metabolismo , Transducción de SeñalRESUMEN
Neurobrucellosis presents in various clinical forms and should always be considered in neurological patients in highly endemic areas such as the Mediterranean basin. Establishing a diagnosis can be challenging since serological testing can sometimes yield negative results. We present a rare case of a seronegative relapse of neurobrucellosis in a patient who had been successfully treated for systemic brucellosis. Oligoclonal bands, an agglutination test, and 16S rRNA sequencing of cerebrospinal fluid proved essential in unmasking a confined central nervous system relapse. This case reinforces the need for establishing diagnostic criteria for neurobrucellosis, which could potentially include oligoclonal bands and an agglutination test on the cerebrospinal fluid.
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Brucelosis , Pruebas de Aglutinación , Brucelosis/diagnóstico , Brucelosis/tratamiento farmacológico , Sistema Nervioso Central , Pruebas Diagnósticas de Rutina , Humanos , ARN Ribosómico 16SRESUMEN
INTRODUCTION: The identification of pregnant women with Gestational Diabetes Mellitus (GDM) who will require insulin therapy, may modify their management to closer monitoring and probable early interventions. The aim of the study was to develop a predictive model for the necessity of insulin treatment in women with GDM. MATERIALS AND METHODS: This was a prospective cohort study. Data from 775 women diagnosed with GDM per the IADPSG criteria were analyzed using logistic regression and a machine learning algorithm, the Classification and Regression Trees (CART). Potential predictors routinely recorded at follow-up visits were tested and used for the development of the model. The resultant model was externally validated using the data from two different perinatology clinics. RESULTS: Preconceptional maternal BMI and morning fasting blood glucose levels at baseline and at 1 h during an Oral Glucose Tolerance Test (OGTT) were independent significant predictors for the treatment modality of GDM. Baseline blood glucose greater than 98 mg/dl and preconceptional maternal Body Mass Index (BMI) between 26 and 31 kg/height2 increased substantially the probability of insulin therapy (odds ratio [OR] 4.04, 95% confidence interval [CI] CI 2.65-6.17 and 2.21, 95%CI 1.42-3.43, respectively). The area under the curve (AUC) for the internal and external validation of the predictive model was 0.74 and 0.77, respectively. CONCLUSIONS: A simple model based on maternal characteristics and the values of an OGTT can predict the need for insulin treatment with accuracy. Overweight women with an abnormal baseline blood glucose at OGTT are at high likelihood for insulin treatment. KEY MESSAGE: Fifteen to 30% of women with Gestational Diabetes Mellitus (GDM) require insulin therapy. Overweight women with baseline blood glucose greater than 98 mg/dl at OGTT are at increased risk for insulin treatment and close monitoring and increased physical exercise are required.
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Diabetes Gestacional/tratamiento farmacológico , Insulina/uso terapéutico , Adulto , Algoritmos , Glucemia/análisis , Índice de Masa Corporal , Diabetes Gestacional/diagnóstico , Femenino , Prueba de Tolerancia a la Glucosa/métodos , Humanos , Modelos Logísticos , Modelos Estadísticos , Oportunidad Relativa , Embarazo , Estudios Prospectivos , Ultrasonografía Prenatal/métodosRESUMEN
BACKGROUND: Acute pancreatitis leads to abdominal hypertension and compartment syndrome. Weeks after the episodes pancreatic fluids sometimes organize to pseudocysts, fluid collections by or in the gland. Aims of the present study were to evaluate the intra-abdominal pressure (IAP) induced by large pancreatic pseudocysts and to examine the effect of their transcutaneous drainage on IAP. METHODS: Twenty seven patients with a pancreatic pseudocyst were included. Nine patients with pseudocysts greater than 1l (group A) had CT drainage and eighteen (volume less than 1l) were the control group. The measurements of group A were taken 6 hours before and every morning after the drainage, while for group B, two measurements were performed, one at the day of the initial CT and one 7 days after. Abdominal compliance (Cabd) was calculated. Data were analyzed using student's t-test. RESULTS: Baseline IAP for group A was 9.3 mmHg (S.D. 1.7 mmHg), while the first post-drainage day (PDD) IAP was 5.1 mmHg (S.D. 0.7 mmHg). The second PDD IAP was 5.6 mmHg (S.D. 0.8 mmHg), the third 6.4 mmH (S.D. 1.2 mmHg)g, the fourth 6.9 mmHg (S.D. 1.6 mmHg), the fifth 7.9 mmHg (S.D. 1.5 mmHg), the sixth 8.2 mmHg (S.D. 1.4 mmHg), and the seventh 8.2 mmHg (S.D. 1.5 mmHg). Group B had baseline IAP 8.0 mmHg (S.D. 1.2 mmHg) and final 8.2 mmHg (S.D. 1.4 mmHg). Cabd after drainage was 185.6 ml/mmHg (SD 47.5 ml/mmHg). IAP values were reduced between the baseline and all the post-drainage measurements in group A. IAPs seem to stabilize after the 5th post-drainage day. Baseline IAP was higher in group A than in group B, while the two values, at day 7, were equivalent. CONCLUSION: The drainage of large pancreatic pseudocyst reduces IAP. Moreover, the IAP seems to rise shortly after the drainage again, but in a way that it remains inferior to the initial value. More chronic changes to the IAP are related to abdominal cavity's properties and have to be further studied.