Intrathecal B cell activation and memory impairment in multiple sclerosis.

BACKGROUND: Cognitive impairment (CI) is a common and disabling feature of people with multiple sclerosis (pwMS), but its underlying mechanisms are heterogenous and not fully understood. A role of infiltrating immune cells in the meninges and brain parenchyma has been hypothesized. This study aimed to explore the hypothesis that intrathecal B cells might influence cognitive performance in pwMS. METHODS: A retrospective study was performed on 39 newly diagnosed pwMS who underwent cerebrospinal fluid (CSF) analysis. Kappa (κ)-index was measured as a biomarker of intrathecal B cell activation. Cognitive performance was assessed using the Brief Repeatable Battery of Neuropsychological Tests (BRBN). Brain T2 lesions number (T2LN) and volume (T2LV) together with brain, cortical grey matter, thalamic and hippocampal volumes were calculated to account for MRI-visible damage. RESULTS: κ-index was higher in pwMS with verbal memory impairment (median 99.6, range 58.5-195.2 vs. median 37.2, range 2.3-396.9, p < 0.001), and it was negatively associated with BRBN tests exploring verbal memory and information processing speed. In multivariate models, higher κ-index was confirmed to be independently associated with worse scores of BRBN tests exploring verbal memory and with a higher probability of verbal memory impairment. CONCLUSION: Intrathecal B cells might drive memory impairment in pwMS independently of brain damage visible on MRI scans.

Impaired neutralizing antibody efficacy of tixagevimab-cilgavimab 150+150 mg as pre-exposure prophylaxis against Omicron BA.5. A real-world experience in booster vaccinated immunocompromised patients.

BACKGROUND: Tixagevimab-cilgavimab has been approved as primary pre-exposure prophylaxis in immunocompromised patients as support or replacement for vaccination, even though the Omicron variant of concern (VOC) was spreading at the time. OBJECTIVES: The aim of our study was to evaluate the post-injection neutralising activity (NT90-Abs titre) against the Omicron BA.5 variant in fully vaccinated immunocompromised patients. STUDY DESIGN: NT90-Abs titres against BA.5 and 20A.EU1 as well as anti-spike and anti-receptor-binding domain IgG were evaluated 0, 14, and 30 d after tixagevimab-cilgavimab administration. The primary end point was NT90-Abs titres ≥ 80 against BA.5 in ≥ 25% of patients, and the secondary end point was NT90-Abs titres ≥ 1280 against 20A.EU1 in >50% of patients on day 14. RESULTS: At baseline, 35.2%, 37.02%, and 32.5% of booster vaccinated patients exhibited undetectable levels of anti-S and anti-RBD IgG antibodies such as NT90-Abs titres against A20.EU1. Moreover, 35 patients (61.5%) had undetectable NT90-Abs titres against BA.5. On day 14, IgG anti-S and anti-RBD levels were 3880 BAU/mL and 776.6 AU/mL, respectively. Only 12.5% of patients met a NT90-Abs titres ≥ 80 against BA.5, whereas the median NT90-Abs titre against 20A.EU1 was 1280. NT90-Abs titres against BA.5 were 64-fold lower than those against A20.EU1. Four patients (7.5%) had a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the 3 months after treatment, all with a time gap between the booster vaccination and injection. CONCLUSIONS: To date, tixagevimab-cilgavimab cannot be considered a substitute for vaccination but may be a useful supporting therapy if the recommended dose for pre-exposure prophylaxis is doubled.

Hypomagnesemia and incident delirium in hospitalized older persons.

BACKGROUND: Altered serum magnesium (Mg) levels in older persons have been hypothesized to have a role in predicting hospitalization and mortality. Hypomagnesemia and delirium are frequent problems in older patients, but no study has evaluated such an association in acute geriatric setting. AIMS: We investigated the impact of hypomagnesemia on the incidence of delirium in an acute geriatric setting. METHODS: This retrospective study was conducted on 209 older hospitalized patients. All subjects underwent a comprehensive geriatric assessment. Mg was measured in serum by routine laboratory methods. The presence of incident delirium was determined by the 4AT screening tool. A logistic regression model was used to assess the association between serum Mg and delirium controlling for multiple covariates. RESULTS: 209 patients (77.9% women) were included in the study. The mean age of the participants was 85.7 ± 6.50 years (range 65-100). 27 subjects (12.9%) developed delirium during the hospitalization, with no difference between genders. Subjects with delirium had lower serum magnesium levels than those without (1.88 ± 0.34 versus 2.04 ± 0.28; p = 0.009). Delirium risk was significantly higher in patients with lower serum magnesium levels (OR 5.80 95% CI 1.450-23.222; p = 0.013), independent of multiple covariates. CONCLUSION: Our data show that low serum Mg level is a good predictor of incident delirium in acute geriatric settings. Present findings have relevant implications for clinical management, highlighting the need for analyzing Mg concentration carefully. Whether Mg supplementation in patients with hypomagnesemia could lead to delirium prevention and/or control needs further investigation.

Inter-Laboratory Concordance of Cerebrospinal Fluid and Serum Kappa Free Light Chain Measurements.

The kappa index (K-Index), calculated by dividing the cerebrospinal fluid (CSF)/serum kappa free light chain (KFLC) ratio by the CSF/serum albumin ratio, is gaining increasing interest as a marker of intrathecal immunoglobulin synthesis. However, data on inter-laboratory agreement of these measures is lacking. The aim was to assess the concordance of CSF and serum KFLC measurements, and of K-index values, across different laboratories. KFLC and albumin of 15 paired CSF and serum samples were analyzed by eight participating laboratories. Four centers used Binding Site instruments and assays (B), three used Siemens instruments and assays (S), and one center used a Siemens instrument with a Binding Site assay (mixed). Absolute individual agreement was calculated using a two-way mixed effects intraclass correlation coefficient (ICC). Cohen's kappa coefficient (k) was used to measure agreement on positive (≥5.8) K-index values. There was an excellent agreement in CSF KFLC measurements across all laboratories (ICC (95% confidence interval): 0.93 (0.87-0.97)) and of serum KFLC across B and S laboratories (ICC: 0.91 (0.73-0.97)), while ICC decreased (to 0.81 (0.53-0.93)) when including the mixed laboratory in the analysis. Concordance for a positive K-Index was substantial across all laboratories (k = 0.77) and within S laboratories (k = 0.71), and very good (k = 0.89) within B laboratories, meaning that patients rarely get discordant results on K-index positivity notwithstanding the testing in different laboratories and the use of different platforms/assays.

Anti-severe acute respiratory syndrome coronavirus-2 adenoviral-vector vaccines trigger subclinical antiplatelet autoimmunity and increase of soluble platelet activation markers.

To slow down the coronavirus disease 2019 (COVID-19) pandemic an unequalled vaccination campaign was initiated. Despite proven efficacy and safety, a rare but potentially fatal complication of adenoviral-vector vaccines, called vaccine-induced immune thrombotic thrombocytopenia (VITT), has emerged the pathogenesis of which seems to be related to the development of platelet-activating anti-platelet factor 4 (PF4) antibodies. While a few studies have evaluated the incidence of anti-PF4 positivity in anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine recipients, to date no studies have assessed whether an antiplatelet immunological response develops and if this associates with platelet and blood clotting activation. We carried out a prospective study in healthy subjects who received the first dose of ChAdOx1 or Ad26.COV2.S or BNT162b2 vaccines to evaluate platelet-specific and non-specific immune response and in vivo platelet activation and blood clotting activation. Individuals receiving ChAdOx1 and, less so, Ad26.COV2.S developed with high frequency auto- or alloantiplatelet antibodies, increased circulating platelet-derived microvesicles and soluble P-selectin associated with mild blood clotting activation. Our study shows that an immunological reaction involving platelets is not uncommon in individuals receiving anti-SARS-CoV-2 vaccination, especially after ChAdOx1 and Ad26.COV2.S, and that it associates with in vivo platelet and blood clotting activation.

Cerebrospinal fluid free light chains compared to oligoclonal bands as biomarkers in multiple sclerosis.

Cerebrospinal fluid (CSF) free light chains (FLC) may be an alternative biomarker to oligoclonal bands (OCB) in multiple sclerosis (MS). Herein, we compared the diagnostic accuracy of CSF OCB and FLC and we tested the prognostic value of FLC in a cohort of 64 MS patients and 106 controls. A κ-index >7.83 was more sensitive but less specific than OCB in discriminating MS patients from controls. Additionally, a κ-index >10.61 performed better than OCB in the discrimination between MS and controls with inflammatory neurological diseases (p < .001). In clinically isolated syndrome (CIS) patients, a κ-index >10.61 significantly predicted time to conversion to MS (p = .020). κ-index might be a valid alternative to OCB as a diagnostic biomarker for MS and might also be a prognostic marker in CIS.

Lower serum levels of IL-13 is associated with increased carotid intima-media thickness in old age subjects.

BACKGROUND: Cardiovascular diseases due to atherosclerosis represent the major cause of disability and mortality in old age subjects. The atherosclerotic process is linked to a low grade of systemic inflammation with the involvement of many cytokines and inflammatory proteins. Among them, evidence from animal studies suggests that IL-13 has a protective property. However, the role of IL-13 in the pathogenesis of atherosclerosis in humans is still unknown. AIMS: With this study, we aim to investigate a potential association between IL-13 and carotid intima-media thickness (IMT) in old age subjects. METHODS: This is a retrospective study conducted among 79 old age subjects (over 75 years old). All subjects underwent IMT assessment by high-resolution B-mode ultrasonography and IL-13 measurement in serum by ELISA. RESULTS: Subjects (41 M/38F) had a mean age of 81.0 ± 4.5 years and were mostly overweight. Stratifying the whole cohort by IMT thickness (IMT ≤ 0.9, n = 17; IMT ≥ 1 and ≤ 1.3, n = 50; IMT ≥ 1.4, n = 12) among the main variables explored, only BMI and triglycerides differed among groups, having subjects with higher IMT significantly higher BMI and lower triglycerides. Serum IL-13 levels significantly differed among groups having subjects with IMT ≥ 1.4 lower levels as compared to other groups (p < 0.0001). In all sample population, IMT values significantly correlate with IL-13 levels (r = - 0.454, p < 0.0001). Indeed, a linear regression analysis showed that independent of age, gender, body mass index, triglycerides, systolic blood pressure, statin use and smoking habit, lower IL-13 serum levels were associated with higher IMT values. CONCLUSIONS: IL-13, an anti-inflammatory cytokine, may have a protective role in the human atherosclerotic process. It could be used as an effective and promising novel therapeutic target development.

Cognitive Decline and Alzheimer's Disease in Old Age: A Sex-Specific Cytokinome Signature.

BACKGROUND: Elevated peripheral levels of different cytokines and chemokines in subjects with Alzheimer's disease (AD), as compared with healthy controls (HC), have emphasized the role of inflammation in such a disease. Considering the cross-talking between the central nervous system and the periphery, the inflammatory analytes may provide utility as biomarkers to identify AD at earlier stages. OBJECTIVE: Using an advanced statistical approach, we can discriminate the interactive network of cytokines/chemokines and propose a useful tool to follow the progression and evolution of AD, also in light of sex differences. METHODS: A cohort of 289 old-age subjects was screened for cytokine and chemokine profiling, measured in plasma, after a thorough clinical and neuropsychological evaluation. A custom algorithm based on Fisher linear discriminant analysis was applied to ascertain a classification signature able to discriminate HC from mild cognitive impairment (MCI) and AD. RESULTS: We observed that a joint expression of three proteins (a "signature" composed by IFN-α2, IL-1α, TNFα) can discriminate HC from AD with an accuracy of 65.24%. Using this signature on MCI samples, 84.93% of them were classified as "non-HC". Stratifying MCI samples by sex, we observed that 87.23% of women were classified as "non-HC", and only 57.69% of males. Indeed, in a scatter plot of IFN-α2 and IL-1α, the HC group was better separated from MCI and AD in women as compared with men. CONCLUSION: These findings suggest that AD is accompanied by a peripheral inflammatory response that can already be present in MCI subjects, thus providing a mean for detecting this at-risk status and allow an anticipated intervention.

Levels of Empathy Orientation after the Implementation of a New Curriculum

Objective: To compare the level of empathy orientation of the students in the Dentistry Program from the Universidad Metropolitana according to gender and levels of education after the implementation of a new curriculum. Material and Methods: An exploratory and transversal research was made. The studied population are the students from the first and the fifth academic year in the Dentistry Undergraduate Program from the Universidad Metropolitana (Barranquilla, Colombia) (n = 371, N = 482; 76.97% of the population) First: 92; Second: 83; Third: 60; Fourth: 71 and Fifth: 65, being females = 235 and males = 136. Data collection was done in March 2016 for the present study and in 2012. The Jefferson Scale of Physician Empathy was applied to participants. Results: For the "Academic Years" factor, the means in the first undergraduate years are similar with an increase in the last two undergraduate years; females have superior values than males. However, the behavior of these means is different when analyzing the combined levels of both factors. The female gender increases steadily in the first four years and decreases in the fifth year; The male gender goes down from first to second place and increases steadily until the fifth year surpassing the female in this last year. Conclusion: The general results obtained on empathy have improved compared to those results from 2012. The questions that obtained significant scores were those related to the cognitive component. This could be explained by the incorporation of a greater number of community activities into vulnerable population.

Thromboelastographic profiles of the premature infants with and without intracranial hemorrhage at birth: a pilot study.

OBJECTIVE: To delineate thromboelastographic profiles of the premature infants with and without intracranial hemorrhage during the first 21 days of life. METHODS: In this study, 49 premature infants (24 female; 25 male) were consecutively admitted at our neonatal intensive care unit during a 6 months period were subject to thromboelastography and standard coagulation assessments at birth and weekly up to 21 days. Sixteen out of 49 infants developed intracranial hemorrhage at birth. RESULTS: The test results of 127/196 were considered eligible for analysis. Overall significant changes of the main thromboelastographic parameters were observed shortly after birth. Newborns with intracranial hemorrhage showed increased thromboelastogram-defined thrombin generation (shorter R and time to maximum amplitude times) from birth onward, suggesting a hypercoagulable state. No significant differences concerning thromboelastographic and coagulation assays parameters were found at birth between infants with and without intracranial hemorrhage, except for higher plasma D-Dimer concentration (p = 0.002) in the former infants. Finally, a positive correlation between clot lysis time and gestational age (Spearman's rho = 0.502, p = 0.002) was observed. CONCLUSIONS: Thromboelastographic profiles of the premature infants suggest an effective hemostatic function during the first post-natal weeks. Further study is needed to determine whether thromboelastography may be more useful than coagulation assays to reflect the bleeding risk of the premature infants.

Diverticulo o dehiscencia de la cicatriz de la cesarea: reporte de seis casos / Diverticuli or dehiscence of cesarean scar

El diagnóstico de deshiscencia o divertículo de la cicatriz de la cesárea es infrecuente. Estas pacientes pueden consultar por sangrado intermenstrual o dolor pélvico y pueden presentar complicaciones en embarazos posteriores (Ruptura uterina, embarazo ectópico y acretismo placentario). Los hallazgos en la ecografía, en la histerosonografía (HSG) o en la histerosalpingografía muestran comunicación entre la cavidad endometrial y la colección de la pared uterina

Esclerosis múltiple: aproximación epidemiológico-genética en habitantes de Antioquia-Colombia. I: Características clinico-epidemiológicas / Multiple sclerosis: an epidemiologic and genetic approach in Antioquia, Colombia

A partir de una cohorte de individuos del departamento de Antioquia, diagnosticados con enfermedad desmielinizante en Colombia, una región tropical con un fuerte componente genético caucásico, se realizó un análisis clínico-epidemiológico y genético con la finalidad de diagnosticar casos de esclerosis multiple (EM) definida, poder determinar las características clínicas y demográficas del conjunto, caracterizarlos étnicamente y evaluar la existencia de posibles desequilibrios de ligamiento a marcadores genéticos sospechosos de estar asociados al desarrollo de EM como el HLA. Este artículo constituye el primer informe clínico, demográfico de los casos diagnosticados con EM definida. 28 individuos se definieron gnosológicamente, 21 de ellos tenían EM definida, cinco con deficiencia de vitamina B12 y dos lupus eritematoso sistémico. El síntoma más frecuente de inicio fue la neuritis óptica. Otras formas de comienzo fueron las alteraciones motoras y sensitivas. Se encontraron diferencias estadísticas significativas en distribución de frecuencia de los síntomas iniciales con otras series descritas en el mundo, lo que podría significar un comportamiento diferente de la esclerosis múltiple

Evaluación de la articulación patelofemoral con RX simple y TAC

Se revisan los diferentes métodos radiológicos y escanográficos para la evaluación de la articulación patelofemoral, comparándose la sensibilidad de las diferentes medidas así como la correlación entre ellas y con el cuadro clínico de los pacientes. Estos datos están basados en un estudio comparativo donde se realizaron estudios radiológicos simples y escanográficos a un grupo de pacientes con sintomatología referente a esta articulación

Higroma quístico fetal: presentación de un caso y revisión de la literatura

Se presenta un caso de higroma quístico cervical asociado a hidrops fetal, diagnosticado mediante ecografía prenatal, Se hace breve revisión de la literatura, haciendo énfasis en las recomendaciones para el diagnóstico y manejo de esta entidad

Hipertensión pulmonar primaria en pacientes con hipertensión portal

Se revisaron las radiografías de tórax de 18 pacientes con hipertensión portal. En 28 por ciento de éstos se encontraron signos radiológicos de hipertensión pulmonar de tipo precapilar. La relación existente entre hipertensión pulmonar primaria e hipertensión portal ha sido establecida en diversos trabajos científicos. En las series publicadas la incidencia de hipertensión pulmonar primaria es menor de la encontrada en estos pacientes. Se revisa la fisiopatología de esta asociación y se postula de manera hipotética el posible papel de la hipoxemia de los residentes a la altura de la ciudad de Bogotá (2.640 mts), como factor coadyuvante en éste fenómeno