A real-world characterization of a cohort with eosinophilic esophagitis: looking for severity biomarkers.

Summary: Background. Eosinophilic esophagitis (EoE) is an immune-mediated chronic esophageal disease, with frequent association with atopy. A validated non/minimally invasive biomarker of disease severity has not been identified. We aimed to determine if sensitization to airborne and food allergens correlates with disease severity, and to evaluate the association between clinical and laboratory characteristics with the severity of EoE. Methods. Retrospective study of EoE patients observed in a differentiated center, 2009-2021. The association between patients' diagnosis age, disease duration before diagnosis, sensitization to airborne/food allergens, serum total IgE and peripheral blood eosinophil values and severe clinical disease (presence of symptoms with a significant impact on quality of life and/or ≥ 1 hospital admission due to EoE complications, namely severe dysphagia, food impaction or esophageal perforation) and histological severe disease (≥ 55 eos/hpf and/or microabscesses in esophageal biopsies) was evaluated. Results. 92 patients were observed, 83% male, 87% atopic. There was a mean delay in diagnosis of 4 years (range 0-31). 84% had aeroallergen sensitization and 71% food sensitization. Food impaction and dysphagia were the most frequent symptoms, and severe clinical disease was observed in 55%. Histologically, 37% had severity criteria. Patients with severe clinical disease had a significantly longer mean disease duration before diagnosis than patients without severe clinical disease (79 vs 15 months, p = 0.021). Patients who described food impaction were significantly older at time of diagnosis than those who have never had impaction (18 vs 9 years, p less than 0.001). There was no significant association (p less than 0.05) between sensitization, serum total IgE and peripheral blood eosinophil values and clinical or histological severity. Conclusions. An older age at diagnosis and a longer disease duration before diagnosis appear to be useful for predicting EoE clinical severity. Despite having been demonstrated a high prevalence of allergic disease, the presence of sensitization to airborne and/or food allergens do not seem to be useful for predicting clinical or histological severity.

Neutralizing Autoantibodies to Type I IFNs in >10% of Patients with Severe COVID-19 Pneumonia Hospitalized in Madrid, Spain.

BACKGROUND: In a recent study, autoantibodies neutralizing type I interferons (IFNs) were present in at least 10% of cases of critical COVID-19 pneumonia. These autoantibodies neutralized most type I IFNs but rarely IFN-beta. OBJECTIVES: We aimed to define the prevalence of autoantibodies neutralizing type I IFN in a cohort of patients with severe COVID-19 pneumonia treated with IFN-beta-1b during hospitalization and to analyze their impact on various clinical variables and outcomes. METHODS: We analyzed stored serum/plasma samples and clinical data of COVID-19 patients treated subcutaneously with IFN-beta-1b from March to May 2020, at the Infanta Leonor University Hospital in Madrid, Spain. RESULTS: The cohort comprised 47 COVID-19 patients with severe pneumonia, 16 of whom (34%) had a critical progression requiring ICU admission. The median age was 71 years, with 28 men (58.6%). Type I IFN-alpha- and omega-neutralizing autoantibodies were found in 5 of 47 patients with severe pneumonia or critical disease (10.6%), while they were not found in any of the 118 asymptomatic controls (p = 0.0016). The autoantibodies did not neutralize IFN-beta. No demographic, comorbidity, or clinical differences were seen between individuals with or without autoantibodies. We found a significant correlation between the presence of neutralizing autoantibodies and higher C-reactive protein levels (p = 5.10e-03) and lower lymphocyte counts (p = 1.80e-02). No significant association with response to IFN-beta-1b therapy (p = 0.34) was found. Survival analysis suggested that neutralizing autoantibodies may increase the risk of death (4/5, 80% vs 12/42, 28.5%). CONCLUSION: Autoantibodies neutralizing type I IFN underlie severe/critical COVID-19 stages in at least 10% of cases, correlate with increased C-RP and lower lymphocyte counts, and confer a trend towards increased risk of death. Subcutaneous IFN-beta treatment of hospitalized patients did not seem to improve clinical outcome. Studies of earlier, ambulatory IFN-beta treatment are warranted.

A cross-sectional study on clinical characteristics and severity of children with COVID-19 admitted to a teaching institute in North India.

Background: SARS-CoV-2 infection presentation in children is usually milder than in adults but can be severe and fatal as well. Data on the pediatric population regarding severity and clinical presentation are still limited, and there is a need to have a better understanding of clinical features, severity, and laboratory parameters. Aims and Objective: To document clinical and laboratory characteristics and outcomes of children with SARS-CoV-2 in a low-middle-income country and to evaluate clinicodemographic factors and biochemical markers associated with severity and mortality. Materials and Methods: A hospital-based cross-sectional study was conducted among 112 COVID-19-positive children at a designated Level-3 center in North India. Clinical characteristics, laboratory parameters, and severity of COVID-19 cases as well as factors associated with the severity of the disease, were analyzed by descriptive statistics and a Chi-square test. Results: The adolescent age group (age 12-18 years) was affected most (64.3%). Male patients accounted for 56.3% of total cases. Fever was the most common symptom (41.1%) followed by cough. Presenting complaints were highest from the respiratory system (32.1%) followed by the gastrointestinal (8.9%) and the neurological system (7.1%). Majority of patients had mild disease (87%) while 13% had the moderate-severe disease. Spo2 < 95% (P = 0.00001), neutrophilia (P < 0.000001), lymphopenia (P < 0.000001), elevated values of C-reactive protein (P < 0.00001), Interleukin-6 (P = 0.002), D- dimer (P = 0.00014) and respiratory symptoms as presenting complaints (P < 0.000001) were found to be significantly associated with severity of disease. Conclusion: The male and adolescent age group was affected most. Presenting complaints were highest from the respiratory system. Unusual presentation may have gastrointestinal or neurological presentation. Most children with COVID-19 had mild disease. Moderate to severe disease was not uncommon. Factors including neutrophilia, lymphopenia, elevated lab values of C-reactive protein, D-dimer, and interleukin-6 had a significant association with the severity of the disease. These biomarkers can help predict the severity of the disease.

Toward Personalized Interventions for Psoriasis Vulgaris: Molecular Subtyping of Patients by Using a Metabolomics Approach.

Aim: Psoriasis vulgaris (PV) is a complicated autoimmune disease characterized by erythema of the skin and a lack of available cures. PV is associated with an increased risk of metabolic syndrome and cardiovascular disease, which are both mediated by the interaction between systemic inflammation and aberrant metabolism. However, whether there are differences in the lipid metabolism between different levels of severity of PV remains elusive. Hence, we explored the molecular evidence for the subtyping of PV according to alterations in lipid metabolism using serum metabolomics, with the idea that such subtyping may contribute to the development of personalized treatment. Methods: Patients with PV were recruited at a dermatology clinic and classified based on the presence of metabolic comorbidities and their Psoriasis Area and Severity Index (PASI) from January 2019 to November 2019. Age- and sex-matched healthy controls were recruited from the preventive health department of the same institution for comparison. We performed targeted metabolomic analyses of serum samples and determined the correlation between metabolite composition and PASI scores. Results: A total of 123 participants, 88 patients with PV and 35 healthy subjects, were enrolled in this study. The patients with PV were assigned to a "PVM group" (PV with metabolic comorbidities) or a "PV group" (PV without metabolic comorbidities) and further subdivided into a "mild PV" (MP, PASI <10) and a "severe PV" (SP, PASI ≥10) groups. Compared with the matched healthy controls, levels of 27 metabolites in the MP subgroup and 28 metabolites in the SP subgroup were found to be altered. Among these, SM (d16:0/17:1) and SM (d19:1/20:0) were positively correlated with the PASI in the MP subgroup, while Cer (d18:1/18:0), PC (18:0/22:4), and PC (20:0/22:4) were positively correlated with the PASI in the SP subgroup. In the PVM group, levels of 17 metabolites were increased, especially ceramides and phosphatidylcholine, compared with matched patients from the PV group. In addition, the correlation analysis indicated that Cer (d18:1/18:0) and SM (d16:1/16:1) were not only correlated with PASI but also has strongly positive correlations with biochemical indicators. Conclusion: The results of this study indicate that patients with PV at different severity levels have distinct metabolic profiles, and that metabolic disorders complicate the disease development. These findings will help us understand the pathological progression and establish strategies for the precision treatment of PV.

Biological markers and follow-up after discharge home of patients with COVID-19 pneumonia. / Marcadores y seguimiento tras alta de urgencias en neumonías COVID-19.

OBJECTIVES: We aimed to analyze the clinical course of patients discharged from our emergency departament (ED) with pneumonia symptoms compatible with a diagnosis of COVID-19. MATERIAL AND METHODS: We followed 102 patients discharged home with a diagnosis of pneumonia compatible with COVID19 between March 12 and 21, 2020, in our hospital in the southern part of the autonomous community of Madrid. Descriptive statistics (medians and interquartile ranges or frequencies, as appropriate) were compiled for the main variables. Treatments and prognoses were compared with 􀁆2, Kruskal-Wallis, or Mann-Whitney tests. The data then underwent logistic regression analysis. RESULTS: Most patients (accounting for 74.5% of the discharges) were treated with hydroxychloroquine alone. The readmission rate was 15.7%; the ED revisiting rate was 25.7%. Admission was associated with an elevated lactate dehydrogenase (LDH) level (P=.011), elevated creatine kinase (CK) (P=.004), and lymphopenia (P=.034). Hypertension and chronic obstructive pulmonary disease were also related to admission. Ischemic heart disease was associated with longer duration of symptoms. CONCLUSION: Lymphopenia, and elevated LDH and CK levels predicted the need for hospital admission better than other traditional biological markers in patients with mild to moderate symptoms. Telephone follow-up proved useful for dealing with the overloading of health care services.

OBJETIVO: Analizar la evolución de los pacientes que fueron dados de alta del servicio de urgencias (SU) con neumonía compatible con COVID-19. METODO: Se realiza el seguimiento de 102 pacientes dados de alta desde SU con diagnóstico de neumonía compatible con COVID-19 entre el 12 y el 21 de marzo de 2020 en un hospital del sur de Madrid. Se describen las principales variables utilizando mediana e intervalo intercuartil o usando frecuencias, según corresponda. La comparación entre tratamientos/pronóstico se realizó utilizando el test ji cuadrado, el test de Kruskal Wallis o el test de Mann-Whitney. Finalmente, se realizó un modelo de regresión logística. RESULTADOS: La mayoría de los pacientes (74,5%) fueron tratados con hidroxicloroquina en monoterapia. La tasa de reingreso fue de 15,7% y de revisita a urgencias de 25,7%. El ingreso se relacionó con un LDL (lactato deshidrogenasa) elevado (p = 0,011), creatincinasa (CK) elevada (p = 0,004) y linfopenia (p = 0,034). La hipertensión y la enfermedad pulmonar obstructiva crónica se relacionaron con el ingreso, y la cardiopatía isquémica fue la comorbilidad que se asoció a mayor duración de la sintomatología. CONCLUSIONES: La linfopenia, LDH y CK pronosticaron mejor la necesidad de ingreso que otros marcadores clásicos en pacientes con clínica leve-moderada. El seguimiento telefónico demostró ser de utilidad ante la sobrecarga de recursos sanitarios.

Affinity proteomics within rare diseases: a BIO-NMD study for blood biomarkers of muscular dystrophies.

Despite the recent progress in the broad-scaled analysis of proteins in body fluids, there is still a lack in protein profiling approaches for biomarkers of rare diseases. Scarcity of samples is the main obstacle hindering attempts to apply discovery driven protein profiling in rare diseases. We addressed this challenge by combining samples collected within the BIO-NMD consortium from four geographically dispersed clinical sites to identify protein markers associated with muscular dystrophy using an antibody bead array platform with 384 antibodies. Based on concordance in statistical significance and confirmatory results obtained from analysis of both serum and plasma, we identified eleven proteins associated with muscular dystrophy, among which four proteins were elevated in blood from muscular dystrophy patients: carbonic anhydrase III (CA3) and myosin light chain 3 (MYL3), both specifically expressed in slow-twitch muscle fibers and mitochondrial malate dehydrogenase 2 (MDH2) and electron transfer flavoprotein A (ETFA). Using age-matched sub-cohorts, 9 protein profiles correlating with disease progression and severity were identified, which hold promise for the development of new clinical tools for management of dystrophinopathies.

Marcadores y seguimiento tras alta de urgencias en neumonías COVID-19 / Biological markers and follow-up after discharge home of patients with COVID-19 pneumonia

Objetivos: Analizar la evolución de los pacientes que fueron dados de alta del servicio de urgencias (SU) con neumonía compatible con COVID-19. Método: Se realiza el seguimiento de 102 pacientes dados de alta desde SU con diagnóstico de neumonía compatible con COVID-19 entre el 12 y el 21 de marzo de 2020 en un hospital del sur de Madrid. Se describen las principales variables utilizando mediana e intervalo intercuartil o usando frecuencias, según corresponda. La comparación entre tratamientos/pronóstico se realizó utilizando el test ji cuadrado, el test de Kruskal Wallis o el test de Mann-Whitney. Finalmente, se realizó un modelo de regresión logística. Resultados: La mayoría de los pacientes (74,5%) fueron tratados con hidroxicloroquina en monoterapia. La tasa de reingreso fue de 15,7% y de revisita a urgencias de 25,7%. El ingreso se relacionó con un LDL (lactato deshidrogena-sa) elevado (p = 0,011), creatincinasa (CK) elevada (p = 0,004) y linfopenia (p = 0,034). La hipertensión y la enferme-dad pulmonar obstructiva crónica se relacionaron con el ingreso, y la cardiopatía isquémica fue la comorbilidad que se asoció a mayor duración de la sintomatología. Conclusión: La linfopenia, LDH y CK pronosticaron mejor la necesidad de ingreso que otros marcadores clásicos en pacientes con clínica leve-moderada. El seguimiento telefónico demostró ser de utilidad ante la sobrecarga de recursos sanitarios. (AU)

Background and objective: We aimed to analyze the clinical course of patients discharged from our emergency departament (ED) with pneumonia symptoms compatible with a diagnosis of COVID-19. Methods: We followed 102 patients discharged home with a diagnosis of pneumonia compatible with COVID19 between March 12 and 21, 2020, in our hospital in the southern part of the autonomous community of Madrid. Descriptive statistics (medians and interquartile ranges or frequencies, as appropriate) were compiled for the main variables. Treatments and prognoses were compared with c2, Kruskal–Wallis, or Mann–Whitney tests. The data then underwent logistic regression analysis. Results: Most patients (accounting for 74.5% of the discharges) were treated with hydroxychloroquine alone. The readmission rate was 15.7%; the ED revisiting rate was 25.7%. Admission was associated with an elevated lactate dehydrogenase (LDH) level (P=.011), elevated creatine kinase (CK) (P=.004), and lymphopenia (P=.034). Hypertension and chronic obstructive pulmonary disease were also related to admission. Ischemic heart disease was associated with longer duration of symptoms. Conclusions: Lymphopenia, and elevated LDH and CK levels predicted the need for hospital admission better than other traditional biological markers in patients with mild to moderate symptoms. Telephone follow-up proved useful for dealing with the overloading of health care services. (AU)