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1.
Artículo en Inglés | MEDLINE | ID: mdl-38569875

RESUMEN

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a demyelinating disorder of the central nervous system. We aimed to evaluate the diagnostic performance of recently proposed MOGAD diagnostic criteria in a real-world patient cohort at a tertiary referral centre. METHODS: We identified all patients who were evaluated at Johns Hopkins and were MOG-IgG seropositive by cell-based assay. We retrospectively applied the proposed MOGAD diagnostic criteria. RESULTS: Among the 122 patients included in this study, 109 fulfilled the diagnostic criteria. Of 64 patients with clear positive MOG-IgG titre, 63 patients also satisfied the supporting clinical or MRI features. Of 58 patients with low positive or unknown MOG-IgG titre, 46 met criteria by fulfilment of the supporting features. The medical records were independently reviewed by two investigators with expertise in demyelinating disease, and patients were assigned empirical clinical diagnoses, with agreement with the application of the MOGAD diagnostic criteria in the majority of cases (90%). CONCLUSIONS: Our findings support the diagnostic utility of the proposed MOGAD diagnostic criteria. Patients with MOGAD met the supporting clinical or MRI features almost universally, which suggests that the criteria can be used to accurately differentiate MOGAD from mimics with low-titre MOG-IgG seropositivity.

2.
Mult Scler ; 30(4-5): 594-599, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38018493

RESUMEN

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a distinct demyelinating disease of the central nervous system. Immunoglobulin (Ig) has been used as a maintenance therapy to prevent relapses in MOGAD, but the impact of Ig on serum MOG-IgG titers is unclear. OBJECTIVE: To characterize the variation in serum MOG-IgG titers after initiation of Ig treatment in people with MOGAD. METHODS: We conducted a retrospective study of 10 patients with a diagnosis of MOGAD and available serum MOG-IgG titers before and after initiation of maintenance Ig treatment. RESULTS: We found that most of the patients remained MOG-IgG seropositive while on Ig treatment with a reduced or unchanged titer, despite a lack of disease activity. CONCLUSIONS: This case series suggests that the mechanism of action of Ig therapy in MOGAD is not exclusively dependent on MOG-IgG titer reduction.


Asunto(s)
Cognición , Investigación , Humanos , Estudios Retrospectivos , Sistema Nervioso Central , Inmunoglobulina G , Glicoproteína Mielina-Oligodendrócito , Autoanticuerpos
3.
Ann Neurol ; 92(3): 476-485, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35703428

RESUMEN

OBJECTIVE: Patients with myelin oligodendrocyte glycoprotein antibody (MOG-IgG)-associated disease (MOGAD) suffer from severe optic neuritis (ON) leading to retinal neuro-axonal loss, which can be quantified by optical coherence tomography (OCT). We assessed whether ON-independent retinal atrophy can be detected in MOGAD. METHODS: Eighty patients with MOGAD and 139 healthy controls (HCs) were included. OCT data was acquired with (1) Spectralis spectral domain OCT (MOGAD: N = 66 and HCs: N = 103) and (2) Cirrus high-definition OCT (MOGAD: N = 14 and HCs: N = 36). Macular combined ganglion cell and inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) were quantified. RESULTS: At baseline, GCIPL and pRNFL were lower in MOGAD eyes with a history of ON (MOGAD-ON) compared with MOGAD eyes without a history of ON (MOGAD-NON) and HCs (p < 0.001). MOGAD-NON eyes had lower GCIPL volume compared to HCs (p < 0.001) in the Spectralis, but not in the Cirrus cohort. Longitudinally (follow-up up to 3 years), MOGAD-ON with ON within the last 6-12 months before baseline exhibited greater pRNFL thinning than MOGAD-ON with an ON greater than 12 months ago (p < 0.001). The overall MOGAD cohort did not exhibit faster GCIPL thinning compared with the HC cohort. INTERPRETATION: Our study suggests the absence of attack-independent retinal damage in patients with MOGAD. Yet, ongoing neuroaxonal damage or edema resolution seems to occur for up to 12 months after ON, which is longer than what has been reported with other ON forms. These findings support that the pathomechanisms underlying optic nerve involvement and the evolution of OCT retinal changes after ON is distinct in patients with MOGAD. ANN NEUROL 2022;92:476-485.


Asunto(s)
Síndromes de Inmunodeficiencia/complicaciones , Glicoproteína Mielina-Oligodendrócito/inmunología , Neuritis Óptica/complicaciones , Degeneración Retiniana/etiología , Estudios de Casos y Controles , Estudios de Cohortes , Humanos , Estudios Longitudinales , Neuritis Óptica/diagnóstico por imagen , Neuritis Óptica/etiología , Retina/diagnóstico por imagen , Neuronas Retinianas , Tomografía de Coherencia Óptica/métodos
4.
Curr Allergy Asthma Rep ; 23(9): 481-496, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37402064

RESUMEN

PURPOSE OF REVIEW: In this review, we provide a comprehensive update on current scientific advances and emerging therapeutic approaches in the field of multiple sclerosis. RECENT FINDINGS: Multiple sclerosis (MS) is a common disorder characterized by inflammation and degeneration within the central nervous system (CNS). MS is the leading cause of non-traumatic disability in the young adult population. Through ongoing research, an improved understanding of the disease underlying mechanisms and contributing factors has been achieved. As a result, therapeutic advancements and interventions have been developed specifically targeting the inflammatory components that influence disease outcome. Recently, a new type of immunomodulatory treatment, known as Bruton tyrosine kinase (BTK) inhibitors, has surfaced as a promising tool to combat disease outcomes. Additionally, there is a renewed interested in Epstein-Barr virus (EBV) as a major potentiator of MS. Current research efforts are focused on addressing the gaps in our understanding of the pathogenesis of MS, particularly with respect to non-inflammatory drivers. Significant and compelling evidence suggests that the pathogenesis of MS is complex and requires a comprehensive, multilevel intervention strategy. This review aims to provide an overview of MS pathophysiology and highlights the most recent advances in disease-modifying therapies and other therapeutic interventions.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Esclerosis Múltiple , Humanos , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/etiología , Infecciones por Virus de Epstein-Barr/patología , Herpesvirus Humano 4
5.
J Neuroophthalmol ; 43(2): 220-226, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-36000788

RESUMEN

BACKGROUND: Anti-NMDA receptor (NMDAR) encephalitis patients have been reported to exhibit visual dysfunction without retinal thinning. The objective of our study was to examine the involvement of the visual pathway structure and function in anti-NMDAR encephalitis by assessing postrecovery visual function and retinal structure, and acute-phase occipital cortex function. METHODS: In this cross-sectional study, patients diagnosed with anti-NMDAR encephalitis per consensus criteria underwent postrecovery visual acuity (VA) testing and optical coherence tomography (OCT) with automated retinal layer segmentation. Clinical data and acute-phase brain 18F-fluorodeoxyglucose (FDG) PET/CT (performed within 90 days of symptom onset, assessed qualitatively and semi-quantitatively) were retrospectively analyzed. VA and OCT measures were compared between anti-NMDAR and age, sex, and race-matched healthy controls (HC). When available, FDG-PET/CT metabolism patterns were analyzed for correlations with VA, and OCT measures. RESULTS: A total of 16 anti-NMDAR (32 eyes) and 32 HC (64 eyes) were included in the study. Anti-NMDAR exhibited lower low-contrast VA (2.5% contrast: -4.4 letters [95% CI; -8.5 to -0.3]; P = 0.04, 1.25% contrast: -6.8 letters [95%CI; -12 to -1.7]; P = 0.01) compared with HC, but no differences were found on OCT-derived retinal layer thicknesses. Acute-phase FDG-PET/CT medial occipital cortex metabolism did not correlate with follow-up low-contrast VA or ganglion cell/inner plexiform layer thickness (GCIPL) (n = 7, 2.5% contrast: r = -0.31; P = 0.50, 1.25% contrast: r = -0.34; P = 0.45, GCIPL: r = -0.04; P = 0.94). CONCLUSIONS: Although the visual system seems to be involved in anti-NMDAR encephalitis, no retinal structural or occipital cortex functional abnormalities seem to be responsible for the visual dysfunction. When detected acutely, occipital lobe hypometabolism in anti-NMDAR encephalitis does not seem to associate with subsequent retrograde trans-synaptic degenerative phenomena, potentially reflecting reversible neuronal/synaptic dysfunction in the acute phase of the illness rather than neuronal degeneration.


Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato , Células Ganglionares de la Retina , Humanos , Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Coherencia Óptica/métodos , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Estudios Retrospectivos , Vías Visuales/diagnóstico por imagen , Estudios Transversales , Fibras Nerviosas , Agudeza Visual
6.
Brain ; 144(12): 3664-3673, 2021 12 31.
Artículo en Inglés | MEDLINE | ID: mdl-34718423

RESUMEN

Disease course in multiple sclerosis is notably heterogeneous, and few prognostic indicators have been consistently associated with multiple sclerosis severity. In the general population, socioeconomic disparity is associated with multimorbidity and may contribute to worse disease outcomes in multiple sclerosis. Herein, we assessed whether indicators of socioeconomic status are associated with disease progression in patients with multiple sclerosis using highly sensitive imaging tools such as optical coherence tomography, and determined whether differential multiple sclerosis management or comorbidity mediate any observed socioeconomic status-associated effects. We included 789 participants with longitudinal optical coherence tomography and low contrast letter acuity (at 1.25 and 2.5%) in whom neighbourhood- (derived via nine-digit postal codes) and participant-level socioeconomic status indicators were available ≤10 years of multiple sclerosis symptom onset. Sensitivity analyses included participants with socioeconomic status indicators available ≤3years of symptom onset (n = 552). Neighbourhood-level indicators included state and national area deprivation indices, median household income and the Agency for Healthcare Research and Quality (AHRQ) Socioeconomic Status Index. Participant-level indicators included education level. Biannual optical coherence tomography scans were segmented to quantify thickness of the composite macular ganglion cell+inner plexiform (GCIPL) layer. We assessed the association between socioeconomic status indicators and GCIPL atrophy or low contrast letter acuity loss using mixed models adjusting for demographic (including race and ethnicity) and disease-related characteristics. We also assessed socioeconomic status indicators in relation to multiple sclerosis therapy changes and comorbidity risk using survival analysis. More disadvantaged neighbourhood-level and patient-level socioeconomic status indicators were associated with faster retinal atrophy. Differences in rate of GCIPL atrophy for individuals in the top quartile (most disadvantaged) relative to the bottom quartile (least) for state area deprivation indices were -0.12 µm/year faster [95% confidence interval (CI): -0.19, -0.04; P = 0.003], for national area deprivation indices were -0.08 µm/year faster (95% CI: -0.15, -0.005; P = 0.02), for household income were -0.11 µm/year faster (95% CI: -0.19, -0.03; P = 0.008), for AHRQ Socioeconomic Status Index were -0.12 µm/year faster (95% CI: -0.19, -0.04) and for education level were -0.17 µm/year faster (95% CI: -0.26, -0.08; P = 0.0002). Similar associations were observed for socioeconomic status indicators and low contrast letter acuity loss. Lower socioeconomic status was associated with higher risk of incident comorbidity during follow-up. Low socioeconomic status individuals had faster rates of therapy escalation, suggesting the association between socioeconomic status and GCIPL atrophy may not be explained by differential contemporaneous multiple sclerosis therapy management. In conclusion, socioeconomic disparity is associated with faster retinal neurodegeneration in multiple sclerosis. As low socioeconomic status was associated with a higher risk of incident comorbidities that may adversely affect multiple sclerosis outcomes, comorbidity prevention may mitigate some of the unfavourable socioeconomic status-associated consequences.


Asunto(s)
Progresión de la Enfermedad , Disparidades en Atención de Salud , Esclerosis Múltiple/patología , Degeneración Retiniana/patología , Factores Socioeconómicos , Humanos , Esclerosis Múltiple/complicaciones , Degeneración Retiniana/etiología , Tomografía de Coherencia Óptica , Agudeza Visual
7.
J Neuroophthalmol ; 42(1): e40-e47, 2022 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-34108402

RESUMEN

BACKGROUND: A limited number of studies have investigated the presence of ongoing disease activity independent of clinical relapses in neuromyelitis optica spectrum disorder (NMOSD), and data are conflicting. The objective of our study was to examine whether patients with aquaporin-4 (AQP4)-IgG seropositive NMOSD exhibit progressive retinal neuroaxonal loss, independently of optic neuritis (ON) attacks. METHODS: In this single-center, longitudinal study, 32 AQP4-IgG+ NMOSD patients and 48 healthy controls (HC) were followed with serial spectral-domain optical coherence tomography and visual acuity (VA) assessments. NMOSD patients with ON less than 6 months before baseline were excluded, whereas data from patients with ON during follow-up were censored at the last visit before ON. VA worsening was defined as a decrease in monocular letter acuity ≥5 letters for high-contrast VA and ≥7 letters for low-contrast VA. Analyses were performed with mixed-effects linear regression models adjusted for age, sex, and race. RESULTS: The median follow-up duration was 4.2 years (interquartile range: 1.8-7.5). Relative to HC, NMOSD eyes had faster peripapillary retinal nerve fiber layer (pRNFL) (ß = -0.25 µm/year faster, 95% confidence interval [CI]: -0.45 to -0.05, P = 0.014) and GCIPL thinning (ß = -0.09 µm/year faster, 95% CI: -0.17 to 0, P = 0.05). This difference seemed to be driven by faster pRNFL and GCIPL thinning in NMOSD eyes without a history of ON compared with HC (GCIPL: ß = -0.15 µm/year faster; P = 0.005; pRNFL: ß = -0.43 µm/year faster, P < 0.001), whereas rates of pRNFL (ß: -0.07 µm/year, P = 0.53) and GCIPL (ß = -0.01 µm/year, P = 0.90) thinning did not differ between NMOSD-ON and HC eyes. Nine NMOSD eyes had VA worsening during follow-up. CONCLUSIONS: In this longitudinal study, we observed progressive pRNFL and GCIPL atrophy in AQP4-IgG+ NMOSD eyes unaffected by ON. These results support that subclinical involvement of the anterior visual pathway may occur in AQP4-IgG+ NMOSD.


Asunto(s)
Neuromielitis Óptica , Neuritis Óptica , Acuaporina 4 , Atrofia/patología , Humanos , Inmunoglobulina G , Estudios Longitudinales , Neuromielitis Óptica/complicaciones , Neuromielitis Óptica/diagnóstico , Neuritis Óptica/diagnóstico , Retina/diagnóstico por imagen , Retina/patología , Tomografía de Coherencia Óptica/métodos
8.
Mult Scler ; 27(10): 1506-1519, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33307993

RESUMEN

BACKGROUND: Sphingolipids are myelin components and inflammatory signaling intermediates. Sphingolipid metabolism may be altered in people with multiple sclerosis (PwMS), but existing studies are limited by small sample sizes. OBJECTIVES: To compare the levels of serum ceramides between PwMS and healthy controls (HCs) and to determine whether ceramide levels correlate with disability status, as well as optical coherence tomography (OCT)-derived rates of retinal layer atrophy. METHODS: We performed targeted lipidomics analyses for 45 ceramides in PwMS (n = 251) and HCs (n = 68). For a subset of PwMS, baseline and 5-year Expanded Disability Status Scale (EDSS) assessments (n = 185), or baseline and serial spectral-domain OCT (n = 180) were assessed. RESULTS: Several ceramides, including hexosylceramides, lactosylceramides, and dihydroceramides, were altered in PwMS compared with HCs. Higher levels of Cer16:0 were associated with higher odds of EDSS worsening at 5 years in univariable (odds ratio (OR) = 3.84, 95% confidence interval (CI) = 1.41-10.43) and multivariable analyses accounting for age, sex, and race (OR = 2.97, 95% CI = 1.03-8.59). Each 1 ng/mL higher concentration of Hex-Cer22:0 and DH-HexCer22:0 was associated with accelerated rates (µm/year) of ganglion cell + inner plexiform layer (-0.138 ± 0.053, p = 0.01; -0.158 ± 0.053, p = 0.003, respectively) and peripapillary retinal nerve fiber layer thinning (-0.305 ± 0.107, p = 0.004; -0.358 ± 0.106, p = 0.001, respectively). CONCLUSION: Ceramide levels are altered in PwMS and may be associated with retinal neurodegeneration and physical disability.


Asunto(s)
Esclerosis Múltiple , Ceramidas , Humanos , Retina , Células Ganglionares de la Retina , Tomografía de Coherencia Óptica
9.
Mult Scler ; 27(11): 1738-1748, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33307967

RESUMEN

BACKGROUND: Prior studies have suggested that subclinical retinal abnormalities may be present in aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive neuromyelitis optica spectrum disorder (NMOSD), in the absence of a clinical history of optic neuritis (ON). OBJECTIVE: Our aim was to compare retinal layer thicknesses at the fovea and surrounding macula between AQP4-IgG+ NMOSD eyes without a history of ON (AQP4-nonON) and healthy controls (HC). METHODS: In this single-center cross-sectional study, 83 AQP4-nonON and 154 HC eyes were studied with spectral-domain optical coherence tomography (OCT). RESULTS: Total foveal thickness did not differ between AQP4-nonON and HC eyes. AQP4-nonON eyes exhibited lower outer nuclear layer (ONL) and inner photoreceptor segment (IS) thickness at the fovea (ONL: -4.01 ± 2.03 µm, p = 0.049; IS: -0.32 ± 0.14 µm, p = 0.029) and surrounding macula (ONL: -1.98 ± 0.95 µm, p = 0.037; IS: -0.16 ± 0.07 µm, p = 0.023), compared to HC. Macular retinal nerve fiber layer (RNFL: -1.34 ± 0.51 µm, p = 0.009) and ganglion cell + inner plexiform layer (GCIPL: -2.44 ± 0.93 µm, p = 0.009) thicknesses were also lower in AQP4-nonON compared to HC eyes. Results were similar in sensitivity analyses restricted to AQP4-IgG+ patients who had never experienced ON in either eye. CONCLUSIONS: AQP4-nonON eyes exhibit evidence of subclinical retinal ganglion cell neuronal and axonal loss, as well as structural evidence of photoreceptor layer involvement. These findings support that subclinical anterior visual pathway involvement may occur in AQP4-IgG+ NMOSD.


Asunto(s)
Neuromielitis Óptica , Acuaporina 4 , Estudios Transversales , Humanos , Inmunoglobulina G , Neuromielitis Óptica/diagnóstico por imagen , Agudeza Visual
10.
J Pediatr Hematol Oncol ; 43(5): 176-179, 2021 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-32890077

RESUMEN

Mucormycosis is an invasive, life-threatening fungal infection that mainly affects immunocompromised hosts. We collected data of pediatric mucormycosis cases from all 7 Greek Hematology-Oncology Departments for the years 2008-2017. Six cases of invasive mucormycosis diagnosed during treatment for malignancies were included in the study. In 4 children (66%) mucormycosis occurred within the first 20 days after diagnosis of the underlying disease. Two cases were classified as proven mucormycosis and 4 as probable. The most frequently recorded species was Rhizopus arrhizus (2 patients), followed by Mucor spp (1), and Lichtheimia spp (1). All patients received liposomal amphotericin B. Combined antifungal treatment was used in 5 cases. Surgical excision was performed in 4 cases (66%). Two patients died at 6 and 12 months after the diagnosis, respectively, 1 (17%) because of mucormycosis. Our data suggest that mucormycosis may occur early after the initiation of intensive chemotherapy in children with malignancies.


Asunto(s)
Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Neoplasias Hematológicas/complicaciones , Mucormicosis/complicaciones , Mucormicosis/tratamiento farmacológico , Adolescente , Niño , Preescolar , Femenino , Neoplasias Hematológicas/inmunología , Humanos , Huésped Inmunocomprometido , Masculino , Mucor/efectos de los fármacos , Mucor/inmunología , Mucor/aislamiento & purificación , Mucorales/efectos de los fármacos , Mucorales/inmunología , Mucorales/aislamiento & purificación , Mucormicosis/inmunología , Rhizopus oryzae/efectos de los fármacos , Rhizopus oryzae/inmunología , Rhizopus oryzae/aislamiento & purificación
11.
J Antimicrob Chemother ; 74(12): 3573-3578, 2019 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-31504563

RESUMEN

BACKGROUND: Posaconazole is a recommended option for antifungal prophylaxis in paediatric patients >12 years of age. However, little is known about plasma exposures and safety following administration of the delayed-release tablets (DRTs) in children and adolescents. METHODS: In a retrospective observational study, we analysed steady-state trough concentrations of posaconazole in all paediatric patients who had received the DRT formulation between May 2015 and December 2018 for antifungal prophylaxis. Dosing was guided by a published population pharmacokinetic model with weight-based dosing. Drug concentrations in plasma were measured by a validated tandem MS method. Liver function and drug discontinuations due to adverse effects were also assessed. RESULTS: A total of 34 patients (21 male, 13 female; median age 12 years, range 5-17 years; median body weight 43.5 kg, range 16-84 kg) undergoing treatment for haemato-oncological disorders (n=23) or immunosuppression for polyarthritis (n=1) or post-allogeneic HSCT (n=11) received posaconazole DRTs for a median of 70 days (range 9-391 days). The median first steady-state trough plasma concentration following model-derived dosing was 1607 ng/mL (range 501-8485 ng/mL) with trough concentrations being above the dosing target of ≥700 ng/mL in 32/34 patients (94%). Considering all (first and subsequent) trough concentrations, target attainment was 90% (63/70 samples). Posaconazole was well tolerated without adverse event-related discontinuations or breakthrough infections. CONCLUSIONS: Administration of posaconazole DRTs to paediatric patients guided by a population pharmacokinetic-derived dosing algorithm resulted in predictable and potentially effective exposures and was well tolerated over prolonged time periods.


Asunto(s)
Antifúngicos/administración & dosificación , Antifúngicos/sangre , Huésped Inmunocomprometido , Triazoles/administración & dosificación , Triazoles/sangre , Administración Oral , Adolescente , Antifúngicos/farmacocinética , Quimioprevención , Niño , Preescolar , Preparaciones de Acción Retardada , Femenino , Humanos , Hígado/efectos de los fármacos , Pruebas de Función Hepática , Masculino , Micosis/prevención & control , Plasma , Estudios Retrospectivos , Comprimidos , Triazoles/farmacocinética
12.
Environ Monit Assess ; 191(5): 317, 2019 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-31041530

RESUMEN

In the present study, we approach the geochemical processes affecting the hydrochemistry and resulting in elevated concentrations of hexavalent chromium (Cr6+) in groundwater of the Psachna basin, central Euboea, Greece. Sixty-five groundwater samples and 16 topsoil (5-20 cm) samples were studied in order to examine groundwater and soil quality in relation to geogenic processes and anthropogenic activities. Specifically, the origin of Cr and Cr6+ in groundwater was investigated by co-evaluating (a) hydrochemical cross plots of major ions; (b) spatial distribution maps of Cl-, Mg2+, NO3-, and Cr6+; (c) multivariate statistical analyses such as factor analysis (FA) and hierarchical cluster analysis (HCA) of groundwater geochemistry; (d) chemical analyses of soil samples; and (e) chemical analyses of fertilizers. The major factors that control the hydrochemistry of the study area are reverse ion exchange, dissolution of silicate minerals, and intense agricultural activities. According to FA, three factors explain 73.2% of the total variance of data, whereas according to HCA, the groundwater samples were classified into three groups indicating both geogenic (water-rock interaction) and anthropogenic (agricultural activities) impact. The high concentration of NO3-, up to 540 mg L-1; the strong positive correlation between NO3- and Cr as well as between NO3- and other parameters such as SO42- and Mg2+ in groundwater samples; and the very high content of P, up to 2444 mg kg-1, in soil samples of the Psachna basin, imply the synergistic, although commonly neglected, role of the use of fertilizers in groundwater quality.


Asunto(s)
Cromo/análisis , Monitoreo del Ambiente/métodos , Fertilizantes/análisis , Agua Subterránea/química , Suelo/química , Contaminantes Químicos del Agua/análisis , Agricultura , Grecia , Intercambio Iónico , Análisis Multivariante
13.
Environ Monit Assess ; 191(8): 509, 2019 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-31342188

RESUMEN

The aim of this paper is to provide a methodology including statistical tools and spatial techniques, in order to identify the various potential sources of chromium (Crtot) in the Sarigkiol basin, Western Macedonia, Greece, where elevated concentrations of Crtot in groundwater have been recorded since 1996. Integrated hydrochemical approach and statistical analyses including Pearson's correlation coefficient, multivariate statistical analyses (factor analysis and hierarchical cluster analysis), and spatial techniques (Moran's I spatial autocorrelation index and bivariate local indicator spatial association cluster map) were applied to evaluate the chemical analyses of 73 water samples, from irrigation wells, natural springs, and surface water. Both natural and anthropogenic sources of Crtot were recorded; the first (ultramafic-dominated environment) is strongly depicted on the natural spring water, in which Crtot concentrations as high as ~ 130 µg/L were recorded, whereas the second (agricultural activities) acts synergistically in the irrigation wells of the Sarigkiol basin, in which strong correlations of Crtot, P, and NO3- were defined. The paper highlights its findings by outlining the potential sources of elevated concentrations of Cr6+ in the Sarigkiol basin, stressing the need for a closer attention on the role of agricultural activities as an important, though commonly neglected, anthropogenic source of Crtot in groundwater.


Asunto(s)
Cromo/análisis , Monitoreo del Ambiente/métodos , Agua Subterránea/química , Ríos/química , Contaminantes Químicos del Agua/análisis , Pozos de Agua , Agricultura , Monitoreo del Ambiente/estadística & datos numéricos , Grecia , Análisis Multivariante , Análisis Espacial
14.
Cureus ; 16(5): e60901, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38910728

RESUMEN

Preeclampsia is a human-specific hypertensive disorder of gestation. It is associated with short-term adverse effects in the fetus and long-term complications in the neonate, mainly due to disrupted blood flow during critical periods of intrauterine development. An ischemic event in the uterus can affect many systems of the fetus, including a small bowel involvement. We present a case of a preterm, small for gestational age neonate with severe intrauterine growth restriction, small bowel stenosis, and volvulus without malrotation, born to a mother with severe preeclampsia.

15.
Diagnostics (Basel) ; 14(7)2024 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-38611595

RESUMEN

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is the most prevalent childhood malignancy. Despite high cure rates, several questions remain regarding predisposition, response to treatment, and prognosis of the disease. The role of intermediary metabolism in the individualized mechanistic pathways of the disease is unclear. We have hypothesized that children with any (sub)type of ALL have a distinct metabolomic fingerprint at diagnosis when compared: (i) to a control group; (ii) to children with a different (sub)type of ALL; (iii) to the end of the induction treatment. MATERIALS AND METHODS: In this prospective case-control study (NCT03035344), plasma and urinary metabolites were analyzed in 34 children with ALL before the beginning (D0) and at the end of the induction treatment (D33). Their metabolic fingerprint was defined by targeted analysis of 106 metabolites and compared to that of an equal number of matched controls. Multivariate and univariate statistical analyses were performed using SIMCAP and scripts under the R programming language. RESULTS: Metabolomic analysis showed distinct changes in patients with ALL compared to controls on both D0 and D33. The metabolomic fingerprint within the patient group differed significantly between common B-ALL and pre-B ALL and between D0 and D33, reflecting the effect of treatment. We have further identified the major components of this metabolic dysregulation, indicating shifts in fatty acid synthesis, transfer and oxidation, in amino acid and glycerophospholipid metabolism, and in the glutaminolysis/TCA cycle. CONCLUSIONS: The disease type and time point-specific metabolic alterations observed in pediatric ALL are of particular interest as they may offer potential for the discovery of new prognostic biomarkers and therapeutic targets.

16.
J Neurol ; 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39066792

RESUMEN

BACKGROUND: The clinical spectrum and diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has evolved in the setting of an optimized anti-MOG-IgG cell-based assay and expert consensus. The McDonald criteria for MS have been revised multiple times to improve the accuracy and specificity of diagnosis on a framework based on clinical presentation, MRI findings, and CSF results. While the uses of MS and MOGAD diagnostic criteria are helpful for typical cases, such utility for patients with overlapping clinical, laboratorial, and imaging features is unknown, posing diagnostic and management uncertainties. OBJECTIVES: To report a multicenter cohort of patients with overlapping phenotypic features of MOGAD and MS and evaluate the application of new MOGAD diagnostic criteria. METHODS: A collaborative retrospective cohort study was performed to identify patients with both positive serum anti-MOG-IgG and fulfillment of the MS revised 2017 McDonald criteria. Clinical and radiographic features of patients fulfilling inclusion criteria were reviewed longitudinally, including relapses, repeated MRI, and MOG-IgG testing in detail to allow the panel of expert opinion to assign to each case. The International MOGAD Panel proposed criteria were applied at onset and last follow-up to each case and compared to the expert author diagnosis assignment based on presentation, clinical and imaging features, and response to treatment. RESULTS: Ten of 225 (4%) MOG-IgG seropositive cases met study inclusion criteria [seven of 10 were female; age at initial event: eight adults (mean age 26.8 years), two adolescents (mean age 14.5 years)]. AQP4-IgG was negative for all. Apart from serum titers of MOG-IgG, distinguishing clinical and radiographic features [i.e., clinical severity of the initial demyelinating event, radiographic features (optic nerve/spine/brain), and presence/absence of lesion normalization on serial scans] led to consensus of three separate classifications differing by degrees of shared features of MOGAD and MS. Patients were classified by expert panel into (1) Classic MOGAD even with MS-like, well-defined brain lesions, when severe events and most T2 lesions normalized (n = 5; MOG-IgG titers 1:100, 1:20, 1:160, 1:40, 1:200); (2) Classic RRMS included cases thought to have likely false positive or clinically irrelevant MOG-IgG, due to mild clinical events and no radiographic normalization of well-defined MS-like lesions (n = 3; MOG titers 1:20, 1:100, 1:40); (3) MOGAD and MS overlapping phenotype was defined by those with a combination of mild and severe clinical events, partial T2 lesion normalization, both well- and ill-defined lesions (n = 2; MOG titers 1:20, 1:100). The application of the International MOGAD Panel criteria categorized five patients (50%) in agreement with expert assignment. One additional patient was classified in agreement to assignment when MOGAD criteria were applied after serial MOG-IgG titers testing. DISCUSSION: While the International MOGAD Panel diagnostic criteria have helped with accuracy for the diagnosis of this condition, in a group of patients seropositive for MOG-IgG with overlapping clinical and imaging features of RRMS criteria review may lead to increased accuracy. Serial serologies, repeated imaging, close attention to clinical course, and response to therapy are possible variables to consider for further refinement of MOGAD diagnostic criteria.

17.
Neurol Neuroimmunol Neuroinflamm ; 11(4): e200257, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38754047

RESUMEN

OBJECTIVES: To assess whether the rate of change in synaptic proteins isolated from neuronally enriched extracellular vesicles (NEVs) is associated with brain and retinal atrophy in people with multiple sclerosis (MS). METHODS: People with MS were followed with serial blood draws, MRI (MRI), and optical coherence tomography (OCT) scans. NEVs were immunocaptured from plasma, and synaptopodin and synaptophysin proteins were measured using ELISA. Subject-specific rates of change in synaptic proteins, as well as brain and retinal atrophy, were determined and correlated. RESULTS: A total of 50 people with MS were included, 46 of whom had MRI and 45 had OCT serially. The rate of change in NEV synaptopodin was associated with whole brain (rho = 0.31; p = 0.04), cortical gray matter (rho = 0.34; p = 0.03), peripapillary retinal nerve fiber layer (rho = 0.37; p = 0.01), and ganglion cell/inner plexiform layer (rho = 0.41; p = 0.006) atrophy. The rate of change in NEV synaptophysin was also correlated with whole brain (rho = 0.31; p = 0.04) and cortical gray matter (rho = 0.31; p = 0.049) atrophy. DISCUSSION: NEV-derived synaptic proteins likely reflect neurodegeneration and may provide additional circulating biomarkers for disease progression in MS.


Asunto(s)
Atrofia , Encéfalo , Vesículas Extracelulares , Esclerosis Múltiple , Retina , Sinaptofisina , Humanos , Masculino , Femenino , Persona de Mediana Edad , Vesículas Extracelulares/metabolismo , Adulto , Encéfalo/patología , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Retina/patología , Retina/diagnóstico por imagen , Retina/metabolismo , Esclerosis Múltiple/patología , Esclerosis Múltiple/metabolismo , Esclerosis Múltiple/diagnóstico por imagen , Sinaptofisina/metabolismo , Tomografía de Coherencia Óptica , Imagen por Resonancia Magnética , Proteínas de Microfilamentos/metabolismo
18.
Environ Sci Pollut Res Int ; 30(30): 74771-74790, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37209349

RESUMEN

The occurrence, mobilization, and origin of Potentially Toxic Eelements (PTEs) in the environment is always a difficult research question that has not been fully addressed to date; solving this problem would be a major achievement for environmental science and pollution research, a significant scientific breakthrough, and an important contribution to environmental analysis and monitoring. The lack of a holistic methodology that uses chemical analysis to determine the origin of each PTE in the environment is the main motivation for this project. Therefore, the hypothesis tested here is to develop a scientific approach applied to each PTE to determine whether its origin is geogenic (i.e., water-rock interaction with dominance of silicate or carbonate mineral phases) or anthropogenic (i.e., agricultural practices, wastewater, industrial activities). A total of 47 groundwater samples from the Psachna Basin in central Euboea, Greece, were used and plotted on geochemical mole ratio diagrams (i.e., Si/NO3 vs. Cl/HCO3) and used to perform a robust geochemical modeling analysis. The proposed method showed that elevated groundwater concentrations of various PTEs in groundwater were mainly related to intensive fertilization (e.g., Cr, U), water-rock interaction (e.g., Ni), and saltwater intrusion. (i.e., As, Se). This work highlights that a comprehensive framework with sophisticated molar ratios combined with modern statistical methods, multi-isotope signatures, and geochemical modeling could provide answers to unresolved scientific questions about the origin of PTEs in water resources and improve environmental resilience.


Asunto(s)
Agua Subterránea , Contaminantes Químicos del Agua , Monitoreo del Ambiente/métodos , Contaminantes Químicos del Agua/análisis , Agua Subterránea/análisis , Agricultura , Agua/análisis
19.
Artículo en Inglés | MEDLINE | ID: mdl-36418179

RESUMEN

BACKGROUND AND OBJECTIVES: Observational studies suggest low levels of 25-hydroxyvitamin D (25[OH]D) may be associated with increased disease activity in people with multiple sclerosis (PwMS). Large-scale genome-wide association studies (GWAS) suggest 25(OH)D levels are partly genetically determined. The resultant polygenic scores (PGSs) could serve as a proxy for 25(OH)D levels, minimizing potential confounding and reverse causation in analyses with outcomes. Herein, we assess the association of genetically determined 25(OH)D and disease outcomes in MS. METHODS: We generated 25(OH)D PGS for 1,924 PwMS with available genotyping data pooled from 3 studies: the CombiRx trial (n = 575), Johns Hopkins MS Center (n = 1,152), and Immune-Mediated Inflammatory Diseases study (n = 197). 25(OH)D-PGS were derived using summary statistics (p < 5 × 10-8) from a large GWAS including 485,762 individuals with circulating 25(OH)D levels measured. We included clinical and imaging outcomes: Expanded disability status scale (EDSS), timed 25-foot walk (T25FW), nine-hole peg test (9HPT), radiologic activity, and optical coherence tomography-derived ganglion cell inner plexiform layer (GCIPL) thickness. A subset (n = 935) had measured circulating 25(OH)D levels. We fitted multivariable models based on the outcome of interest and pooled results across studies using random effects meta-analysis. Sensitivity analyses included a modified p value threshold for inclusion in the PGS (5 × 10-5) and applying Mendelian randomization (MR) rather than using PGS. RESULTS: Initial analyses demonstrated a positive association between generated 25(OH)D-PGS and circulating 25(OH)D levels (per 1SD increase in 25[OH]D PGS: 3.08%, 95% CI: 1.77%, 4.42%; p = 4.33e-06; R2 = 2.24%). In analyses with outcomes, we did not observe an association between 25(OH)D-PGS and relapse rate (per 1SD increase in 25[OH]D-PGS: 0.98; 95% CI: 0.87-1.10), EDSS worsening (per 1SD: 1.05; 95% CI: 0.87-1.28), change in T25FW (per 1SD: 0.07%; 95% CI: -0.34 to 0.49), or change in 9HPT (per 1SD: 0.09%; 95% CI: -0.15 to 0.33). 25(OH)D-PGS was not associated with new lesion accrual, lesion volume or other imaging-based outcomes (whole brain, gray, white matter volume loss or GCIPL thinning). The results were similarly null in analyses using other p value thresholds or those applying MR. DISCUSSION: Genetically determined lower 25(OH)D levels were not associated with worse disease outcomes in PwMS and raises questions about the plausibility of a treatment effect of vitamin D in established MS.


Asunto(s)
Esclerosis Múltiple , Humanos , Esclerosis Múltiple/genética , Estudio de Asociación del Genoma Completo , Vitamina D , Encéfalo , Factores de Riesgo
20.
Curr Eye Res ; 48(3): 312-319, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36440535

RESUMEN

PURPOSE: To quantify the associations of myopia with longitudinal changes in retinal layer thicknesses in people with multiple sclerosis (PwMS) and healthy controls (HC). METHODS: A cohort of PwMS and HC with recorded refractive error (RE) prospectively scanned on Cirrus HD-OCT at the Johns Hopkins MS Center was assessed for inclusion. Exclusion criteria included OCT follow-up < 6 months, ocular comorbidities, incidental OCT pathologies, and inadequate scan quality. Eyes were classified as having high myopia (HM) (RE≤ -6 diopters), low myopia (LM) (RE> -6 and ≤ -3 diopters), or no myopia (NM) (RE> -3 and ≤ +2.75). Linear mixed-effects regression models were used in analyses. RESULTS: A total of 213 PwMS (eyes: 67 HM, 98 LM, 207 NM) and 80 HC (eyes: 26 HM, 37 LM, 93 NM) were included. Baseline average ganglion cell/inner plexiform (GCIPL) and peri-papillary retinal nerve fiber layer (pRNFL) thicknesses were lower in MS HM compared with MS NM (diff: -3.2 µm, 95% CI: -5.5 to -0.8, p = 0.008 and -5.3 µm, 95% CI: -9.0 to -1.7, p = 0.004, respectively), and similarly in HC HM, as compared with HC NM. Baseline superior, inferior, and nasal pRNFL thicknesses were lower in HM compared with NM, while temporal pRNFL thickness was higher, both in MS and HC (MS: 7.1 µm, 95% CI: 2.7-11.6, p = 0.002; HC: 4.7 µm, 95% CI: -0.3 to 9.7, p = 0.07). No longitudinal differences in rates of GCIPL change were noted between HM and LM vs. NM, either in MS or HC. CONCLUSION: Cross-sectional differences in average GCIPL and pRNFL thicknesses are commonly seen in people with HM as compared to reference normative values from people with NM and can lead to false attribution of pathology if RE is not taken into account. However, our study suggests that longitudinal changes in average GCIPL thickness in PwMS with myopia are similar in magnitude to PwMS with NM, and therefore are appropriate for monitoring disease-related pathology.


Asunto(s)
Esclerosis Múltiple , Miopía , Humanos , Tomografía de Coherencia Óptica/métodos , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/complicaciones , Estudios Transversales , Células Ganglionares de la Retina/patología , Fibras Nerviosas/patología , Miopía/patología
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