Dysimmunity in common variable immunodeficiency is associated with alterations in oral, respiratory, and intestinal microbiota.

Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency characterized by decreased immunoglobulins and recurrent infections. Its aetiology remains unknown, and some patients present with severe non-infectious autoimmune or inflammatory complications with elevated associated morbimortality. Recently, intestinal dysbiosis has been proposed as a driver of immune dysregulation. In this study, we assessed the oral, respiratory, and gastrointestinal microbiota of 41 CVID patients (24 with dysimmune and 17 with infection complications) and 15 healthy volunteers using 16S rRNA gene sequencing to explore associations between microbiome profiles and CVID phenotypes. Profound differences in the composition of the microbiota in saliva, sputum, and stool were detected between dysimmune CVID patients and healthy individuals. Globally, respiratory species diversity and faecal bacterial richness were lower in CVID individuals with immune complications. Although a single species could not be identified as a robust predictor of dysimmunity, a combination of around 5-7 bacterial species in each type of sample could predict this severe phenotype with an accuracy of around 90% in the study population. Our study provides new insights into these previously unexplored but highly interrelated ecological niches among themselves and with patient profiles. Our data suggest that this disease-related systemic dysbiosis could be implicated in the immune dysregulation associated with severe cases of CVID.

Current clinical spectrum of common variable immunodeficiency in Spain: The multicentric nationwide GTEM-SEMI-CVID registry.

Common variable immunodeficiency (CVID) constitutes a heterogenic group of primary immunodeficiency disorders with a wide-ranging clinical spectrum. CVID-associated non-infectious morbidity constitutes a major challenge requiring a full understanding of its pathophysiology and its clinical importance and global variability, especially considering the broad clinical, genetic, and regional heterogeneity of CVID disorders. This work aimed to develop a nationwide, multicenter, retrospective study over a 3-year period describing epidemiological, clinical, laboratory, therapeutic, and prognostic features of 250 CVID patients in Spain. The mean diagnostic delay was around 10 years and most patients initially presented with infectious complications followed by non-infectious immune disorders. However, infectious diseases were not the main cause of morbimortality. Non-infectious lung disease was extraordinarily frequent in our registry affecting approximately 60% of the patients. More than one-third of the patients in our cohort showed lymphadenopathies and splenomegaly in their follow-up, and more than 33% presented immune cytopenias, especially Evans' syndrome. Gastrointestinal disease was observed in more than 40% of the patients. Among biopsied organs in our cohort, benign lymphoproliferation was the principal histopathological alteration. Reaching 15.26%, the global prevalence of cancer in our registry was one of the highest reported to date, with non-Hodgkin B lymphoma being the most frequent. These data emphasize the importance of basic and translational research delving into the pathophysiological pathways involved in immune dysregulation and diffuse lymphocytic infiltration. This would reveal new tailored strategies to reduce immune complications, and the associated healthcare burden, and ensure a better quality of life for CVID patients.

Norovirus infection as a model of chronic or recurrent infection in common variable immunodeficiency

Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency (PID) in general population. PID are genetic diseases that share a dysfunction in the immune system entailing a greater risk of both chronic and recurrent infections. These patients can also develop chronic gastrointestinal infections caused by norovirus with persistent viral dissemination, which can be detect ed months after primoinfection. Additionally, a proportion of CVID patients show a typical severe enteropathy presenting with recurrent diarrhoea, intestinal malabsorption, inflammatory lesions, and villous atrophy. Some studies have related this enteropathy with chronic intestinal infection caused by norovirus. (AU)

Integrating Clinics, Laboratory, and Imaging for the Diagnosis of Common Variable Immunodeficiency-Related Granulomatous-Lymphocytic Interstitial Lung Disease.

Background: Granulomatous-lymphocytic interstitial lung disease (GLILD) is a distinct clinic-radio-pathological interstitial lung disease (ILD) that develops in 9% to 30% of patients with common variable immunodeficiency (CVID). Often related to extrapulmonary dysimmune disorders, it is associated with long-term lung damage and poorer clinical outcomes. The aim of this study was to explore the potential use of the integration between clinical parameters, laboratory variables, and developed CT scan scoring systems to improve the diagnostic accuracy of non-invasive tools. Methods: A retrospective cross-sectional study of 50 CVID patients was conducted in a referral unit of primary immune deficiencies. Clinical variables including demographics and comorbidities; analytical parameters including immunoglobulin levels, lipid metabolism, and lymphocyte subpopulations; and radiological and lung function test parameters were collected. Baumann's GLILD score system was externally validated by two observers in high-resolution CT (HRCT) scans. We developed an exploratory predictive model by elastic net and Bayesian regression, assessed its discriminative capacity, and internally validated it using bootstrap resampling. Results: Lymphadenopathies (adjusted OR 9.42), splenomegaly (adjusted OR 6.25), Baumann's GLILD score (adjusted OR 1.56), and CD8+ cell count (adjusted OR 0.9) were included in the model. The larger range of values of the validated Baumann's GLILD HRCT scoring system gives it greater predictability. Cohen's κ statistic was 0.832 (95% CI 0.70-0.90), showing high concordance between both observers. The combined model showed a very good discrimination capacity with an internally validated area under the curve (AUC) of 0.969. Conclusion: Models integrating clinics, laboratory, and CT scan scoring methods may improve the accuracy of non-invasive diagnosis of GLILD and might even preclude aggressive diagnostic tools such as lung biopsy in selected patients.

Eosinofilia, elevación de proteína C-reactiva y fiebre inducidos por clozapina / Clozapine-induced eosinophilia, elevated C-reactive protein and fever

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Prognostic Factors of Death in 151 Adults With Hemophagocytic Syndrome: Etiopathogenically Driven Analysis.

OBJECTIVE: To characterize the etiologies and clinical features at diagnosis of patients with hemophagocytic lymphohistiocytosis (HLH) and correlate these baseline features with survival using an etiopathogenically guided multivariable model. PATIENTS AND METHODS: The Spanish Group of Autoimmune Diseases HLH Study Group, formed in 2013, is aimed at collecting adult patients with HLH diagnosed in internal medicine departments between January 3, 2013, and October 28, 2017. RESULTS: The cohort consisted of 151 patients (91 men; mean age, 51.4 years). After a mean follow-up of 17 months (range, 1-142 months), 80 patients died. Time-to-event analyses for death identified a worse survival curve for patients with neoplasia (P<.001), mixed microbiological infections (P=.02), and more than 1 infection (P=.01) and glucocorticoid monotherapy (P=.02). According to univariate analyses, platelets of less than 100,000/mm3 (hazard ratio [HR], 3.39; 95% CI, 1.37-8.40), leukopenia (HR, 1.81; 95% CI, 1.01-3.23), severe hyponatremia (HR, 1.61; 95% CI, 1.02-2.54), disseminated intravascular coagulation (HR, 1.87; 95% CI, 1.05-3.34), bacterial infection (HR, 1.99; 95% CI, 1.09-3.63), mixed microbiological infections (HR, 3.42; 95% CI, 1.38-8.46), and 2 or more infectious triggers (HR, 2.95; 95% CI, 1.43-6.08) were significantly associated with death. In contrast, peripheral adenopathies (HR, 0.63; 95% CI, 0.40-0.98) and the immunosuppressive drug/intravenous immunoglobulin/biological therapies (HR, 0.44; 95% CI, 0.20-0.96) were protective against all-cause mortality. Multivariable Cox proportional hazards regression analysis identified 2 or more infectious triggers (HR, 3.14; 95% CI, 1.28-7.68) as the only variable independently associated with death. CONCLUSION: The mortality rate of adult patients diagnosed with HLH exceeds 50%. Infection with more than 1 microbiological agent was the only independent variable associated with mortality irrespective of the underlying disease, epidemiological profile, clinical presentation, and therapeutic management.

Prevalencia de desnutrición en una unidad de media y larga estancia hospitalaria / Prevalence of malnutrition in a mind-long term stay unit

Introducción: La desnutrición es un problema de salud frecuente, especialmente en el ámbito hospitalario donde se asocia con estancias más prolongadas y mayor tasa de morbi-mortalidad. Por otro lado, los avances científicos actuales y la mayor expectativa de vida, han producido un aumento progresivo de unidades de media y larga estancia (UMLE). Objetivos: Determinar la prevalencia de desnutrición en una UMLE mediante el uso del MNA y la VGS, así como analizar los factores/características clínicas asociadas a la misma y sus repercusiones. Métodos: Estudio transversal, descriptivo de una cohorte formada por 201 pacientes ingresados en la UMLE de un Hospital universitario de forma consecutiva durante 12 meses. Se recogieron variables clínicas, antropométricas, bioquímicas e historia nutricional, así como escala de comorbilidad de Charlson, escala cognitiva de Pfeiffer, escala funcional de Barthel y presencia de edemas, ascitis y úlceras por presión. El estado nutricional fue evaluado en las primeras 24-72 horas de ingreso mediante el MNA y la VGS. La presencia de disfagia se evaluó mediante el cuestionario EAT-10 y el MECV-V. Resultados: La prevalencia global de desnutrición fue del 76,6%, siendo la desnutrición mixta grave la más prevalente (20.4%). Los pacientes desnutridos tenían más edad (p=0,002), mayor grado de dependencia (p<0,0001), mayor deterioro cognitivo (p<0,0001) y mayor prevalencia de infecciones urinarias (p=0,026) y presencia de escaras (p=0,005). En el 43.6% de los pacientes se diagnosticó disfagia (MECV-V patológico). Conclusiones: La prevalencia de desnutrición es muy elevada en unidades médicas de larga estancia, generalmente es grave y se asocia con mayor comorbilidad. Casi la mitad de los pacientes presentaban disfagia. El cribaje y valoración nutricional son imprescindibles para el adecuado diagnóstico y tratamiento del estado nutricional en estas unidades (AU)

Introduction: Malnutrition is a common health problem, especially in hospitalized patients, where it’s associated with longer hospital stays and higher rates of morbidity and mortality. Furthermore, current scientific advances and life expectancy increase, have produced a progressive increase of mid- to long-term stay units (UMLE). Aims: To determinate the prevalence of malnutrition on admission to a mid- to long-term stay unit, using MNA and VGS and to analyze the possible factors/clinical features associated with malnutrition and its consequences. Methods: Descriptive and transversal study conducted with 201 patients admitted consecutively for 12 months in an Universitary Hospital mid- to long-term stay unit (Valencia). Clinical, anthropometric, biochemical and nutritional history data were registered, as well as Charlson comorbidity scale, Pfeiffer cognitive scale, Barthel functional scale and presence of edema, ascitis and pressure ulcers. Nutritional status was evaluated in the first 24-72 hours of admission using MNA and VGS. Dysphagia was evaluated using EAT-10 and MECV-V questionaires. Results: The overall rate of malnutrition was 76,6%, being severe protein energy malnutrition the most common type (20,4%). Malnourished patients were older (p=0,002), presented greater dependence (p<0,0001) and greater cognitive impairment (p<0,0001) and they had higher prevalence of urinary tract infections (p=0,026) and presence of pressure ulcer (p=0,005). Dysphagia was diagnosed in 43.6% of the patients. Conclusions: The prevalence of malnutrition is higher Correspondencia: María Argente Pla. in a mid to long-term stay unit, is usually severe and as sociated with greater comorbidity. Almost half of the patients had dysphagia. Nutritional assessment is essential for establishing the correct diagnosis and treatment of the nutritional status in mid to - long term stay unit (AU)

[Prevalence of malnutrition in a mid-long term stay unit]. / Prevalencia de desnutrición en una unidad de media y larga estancia hospitalaria.

INTRODUCTION: Malnutrition is a common health problem, especially in hospitalized patients, where it's associated with longer hospital stays and higher rates of morbidity and mortality. Furthermore, current scientific advances and life expectancy increase, have produced a progressive increase of mid- to long-term stay units (UMLE). AIMS: To determinate the prevalence of malnutrition on admission to a mid- to long-term stay unit, using MNA and VGS and to analyze the possible factors/clinical features associated with malnutrition and its consequences. METHODS: Descriptive and transversal study conducted with 201 patients admitted consecutively for 12 months in an Universitary Hospital mid- to long-term stay unit (Valencia). Clinical, anthropometric, biochemical and nutritional history data were registered, as well as Charlson comorbidity scale, Pfeiffer cognitive scale, Barthel functional scale and presence of edema, ascitis and pressure ulcers. Nutritional status was evaluated in the first 24-72 hours of admission using MNA and VGS. Dysphagia was evaluated using EAT-10 and MECV-V questionnaires. RESULTS: The overall rate of malnutrition was 76,6%, being severe protein energy malnutrition the most common type (20,4%). Malnourished patients were older (p=0,002), presented greater dependence (p.

Introducción: La desnutrición es un problema de salud frecuente, especialmente en el ámbito hospitalario donde se asocia con estancias más prolongadas y mayor tasa de morbi-mortalidad. Por otro lado, los avances científicos actuales y la mayor expectativa de vida, han producido un aumento progresivo de unidades de media y larga estancia (UMLE). Objetivos: Determinar la prevalencia de desnutrición en una UMLE mediante el uso del MNA y la VGS, así como analizar los factores/características clínicas asociadas a la misma y sus repercusiones. Métodos: Estudio transversal, descriptivo de una cohorte formada por 201 pacientes ingresados en la UMLE de un Hospital universitario de forma consecutiva durante 12 meses. Se recogieron variables clínicas, antropométricas, bioquímicas e historia nutricional, así como escala de comorbilidad de Charlson, escala cognitiva de Pfeiffer, escala funcional de Barthel y presencia de edemas, ascitis y úlceras por presión. El estado nutricional fue evaluado en las primeras 24-72 horas de ingreso mediante el MNA y la VGS. La presencia de disfagia se evaluó mediante el cuestionario EAT-10 y el MECV-V. Resultados: La prevalencia global de desnutrición fue del 76,6%, siendo la desnutrición mixta grave la más prevalente (20.4%). Los pacientes desnutridos tenían más edad (p=0,002), mayor grado de dependencia (p.

Hepatitis aguda colestásica por propiltiouracilo / No disponible

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