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"Echevarria, Ana"
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Treatments for multi-system inflammatory syndrome in children — discharge, fever, and second-line therapies
Scarce evidence exists about the best treatment for multi-system inflammatory syndrome (MIS-C). We analyzed the effects of steroids, intravenous immunoglobulin (IVIG), and their combination on the probability of discharge over time, the probability of switching to second-line treatment over time, and the persistence of fever 2 days after treatment. We did a retrospective study to investigate the effect of different treatments on children with MIS-C from 1 March 2020 to 1 June 2021. We estimated the time-to-event probability using a Cox model weighted by propensity score to balance the baseline characteristics. Thirty of 132 (22.7%) patients were initially treated with steroids alone, 29/132 (21.9%) with IVIG alone, and 73/132 (55%) with IVIG plus steroids. The probability of early discharge was higher with IVIG than with IVIG plus steroids (hazard ratio [HR] 1.65, 95% CI 1.11–2.45,
p
= 0.013), but with a higher probability of needing second-line therapy compared to IVIG plus steroids (HR 3.05, 95% CI 1.12–8.25,
p
= 0.028). Patients on IVIG had a higher likelihood of persistent fever than patients on steroids (odds ratio [OR] 4.23, 95% CI 1.43–13.5,
p
= 0.011) or on IVIG plus steroids (OR 4.4, 95% CI 2.05–9.82,
p
< 0.001). No differences were found for this endpoint between steroids or steroids plus IVIG.
Conclusions
: The benefits of each approach may vary depending on the outcome assessed. IVIG seemed to increase the probability of earlier discharge over time but also of needing second-line treatment over time. Steroids seemed to reduce persistent fever, and combination therapy reduced the need for escalating treatment.
What is Known:
• Steroids plus intravenous immunoglobulin, compared with intravenous immunoglobulin alone for multi-system inflammatory syndrome (MIS-C) might reduce the need for hemodynamic support and the duration of fever, but the certainty of the evidence is low.
What is New:
• Intravenous immunoglobulin, steroids, and their combination for MIS-C may have different outcomes.
•
In this study, intravenous immunoglobulin increased the probability of discharge over time, steroids reduced persistent fever, while combination therapy reduced the need for second-line treatments.
Journal Article
الوجود الإسلامي في مدينة آبلة من القرن الحادي عشر إلى القرن السادس عشر
يتناول الكتاب فترة تاريخية لم تحظ من الباحثين العرب بكثير من الاهتمام هي فترة المدجنين أي مسلمي الأندلس الذين عاشوا في ممالك مسيحية في شمال شبه جزيرة إيبيريا على مدى ثمانية فصول وقعت في مائتين وثماني صفحات تتناول جوانب تشمل وصف المنطقة التي سكنها المدجنون، وحديث عن آبلة كمنطقة حدودية خلال القرنين الحادي عشر والثاني عشر، ووضع مسلمي آبلة تحت النفوذ الكنسي في القرنين الثاني عشر والثالث عشر، وتطور جماعة آبلة، وفهم مدجني شمال قشتالة للفقه الإسلامي، وأداء المدجنين للشعائر الاسلامية، وبناء الأسرة المدجنة، ثم تراث المدجنين الثقافي.
BOOK
Ex vivo effect of JAK inhibition on JAK-STAT1 pathway hyperactivation in patients with dominant-negative STAT3 mutations
Purpose
STAT1 gain-of-function (GOF) and dominant-negative (DN) STAT3 syndromes share clinical manifestations including infectious and inflammatory manifestations. Targeted treatment with Janus-kinase (JAK) inhibitors shows promising results in treating STAT1 GOF-associated symptoms while management of DN STAT3 patients has been largely supportive. We here assessed the impact of ruxolitinib on the JAK-STAT1/3 pathway in DN STAT3 patients’ cells.
Methods
Using flow cytometry, immunoblot, qPCR, and ELISA techniques, we examined the levels of basal STAT1 and phosphorylated STAT1 (pSTAT1) of cells obtained from DN STAT3, STAT1 GOF patients, and healthy donors following stimulation with type I/II interferons (IFNs) or interleukin (IL)-6. We also describe the impact of ruxolitinib on cytokine-induced STAT1 signaling in these patients.
Results
DN STAT3 and STAT1 GOF resulted in a similar phenotype characterized by increased STAT1 and pSTAT1 levels in response to IFNα (CD3
+
cells) and IFNγ (CD14
+
monocytes). STAT1-downstream gene expression and C-X-C motif chemokine 10 secretion were higher in most DN STAT3 patients upon stimulation compared to healthy controls. Ex vivo treatment with the JAK1/2-inhibitor ruxolitinib reduced cytokine responsiveness and normalized STAT1 phosphorylation in DN STAT3 and STAT1 GOF patient’ cells. In addition, ex vivo treatment was effective in modulating STAT1 downstream signaling in DN STAT3 patients.
Conclusion
In the absence of effective targeted treatment options for AD-HIES at present, modulation of the JAK/STAT1 pathway with JAK inhibitors may be further explored particularly in those AD-HIES patients with autoimmune and/or autoinflammatory manifestations.
Journal Article
Characterization of methicillin‐resistant Staphylococcus aureus strains colonizing the nostrils of Spanish children
Objective To characterize the Staphylococcus aureus strains colonizing healthy Spanish children. Methods Between March and July 2018, 1876 Spanish children younger than 14 years attending primary healthcare centers were recruited from rural and urban areas. Staphylococcus aureus colonization of the anterior nostrils was analyzed. MecA and mecC genes, antibiotic susceptibility, and genotyping according to the spa were determined in all strains, and the following toxins were examined: Panton‐Valentine leucocidin (pvl), toxic shock syndrome toxin (tst), and exfoliative toxins (eta, etb, etd). Multilocus sequence typing (MLST) and staphylococcal cassette chromosome (SCCmec) typing were performed on methicillin‐resistant Staphylococcus aureus (MRSA) strains, as well as pulsed‐field gel electrophoresis (PFGE). Results 619 strains were isolated in 1876 children (33%), and 92% of them were sent for characterization to the Spanish National Centre of Microbiology (n = 572). Twenty (3.5%) of these strains were mecA‐positive. Several spa types were detected among MRSA, being t002 the most frequently observed (30%), associating with SCCmec IVc. Among MSSA, 33% were positive for tst, while only 0.73% were positive for pvl. The 20 MRSA strains were negative for pvl, and 6 (30%) harbored the tst gene. Conclusions methicillin‐resistant Staphylococcus aureus nasal colonization in Spanish children is rare, with t002 being the most observed spa type, associated with SCCmec IVc. None of the MRSA strains produced pvl, but up to 30% of S. aureus strains were positive for tst. This is one of the largest epidemiological studies in which we have screened up to 1876 healthy Spanish children for methicillin‐resistant Staphylococcus aureus (MRSA) colonization. All the isolated strains have been characterized by analyzing their genotype, the presence of mecA and mecC genes, and their antibiotic susceptibility. In addition, Panton‐Valentine leucocidin, toxic shock syndrome toxin, and exfoliative toxins production were analyzed. This epidemiological surveillance study leads to a better understanding of the strain flow and the rate of MRSA nasal carriage among Spanish children, and the prevalence of virulence genes and antimicrobial sensitivities of colonizing strains throughout the country.
Journal Article
Risk factors for antibiotic-resistant bacteria colonisation in children with chronic complex conditions
To assess drug-resistant bacterial colonisation rates and associated risk factors in children with complex chronic conditions admitted to a national reference unit in Spain. Cross-sectional study that included all children admitted to our unit from September 2018 to July 2019. Rectal swabs were obtained to determine multidrug-resistant Gram-negative bacilli (MR-GNB) colonisation, and nasal swab to determine
S. aureus
and methicillin-resistant
S. aureus
(MRSA) colonisation. Medical records were reviewed. 100 children were included, with a median of four complex chronic conditions. Sixteen percent had
S. aureus
colonisation, including two MRSA.
S. aureus
colonisation was associated with technology-dependent children, while being on antibiotic prophylaxis or having undergone antibiotic therapy in the previous month were protective factors. The prevalence of MR-GNB colonisation was 27%, which was associated with immunosuppressive therapy (aOR 31; 2.02–47];
p
= 0.01), antibiotic prophylaxis (aOR 4.56; 1.4–14.86;
p
= 0.012), previously treated skin-infections (aOR 2.9; 1.07–8.14;
p
= 0.03), surgery in the previous year (aOR 1.4; 1.06–1.8;
p
= 0.014), and hospital admission in the previous year (aOR 1.79; [1.26–2.56];
p
= 0.001). The rate of
S. aureus
nasal colonisation in this series was not high despite the presence of chronic conditions, and few cases corresponded to MRSA. Antibiotic prophylaxis, immunosuppressive therapies, history of infections, previous surgeries, and length of admission in the previous year were risk factors for MR-GNB colonisation.
Journal Article
Bat-Associated Hemotropic Mycoplasmas in Immunosuppressed Children, Spain, 2024
We report the detection of hemotropic mycoplasmas in 4 immunosuppressed pediatric patients in Spain: 2 solid organ transplant recipients, 1 hematopoietic stem cell transplant recipient, and 1 cancer patient. Sequences were 100% identical to a strain previously identified in Miniopterus schreibersii bats, which raises concerns about unnoticed zoonotic transmission.
Journal Article
Humoral and cellular immune response to mRNA SARS-CoV-2 BNT162b2 vaccine in adolescents with rheumatic diseases
Background
Data about safety and efficacy of the mRNA SARS-CoV-2 vaccine in adolescents with rheumatic diseases (RD) is scarce and whether these patients generate a sufficient immune response to the vaccine remains an outstanding question.
Objective
To evaluate safety and humoral and cellular immunity of the BNT162b2 vaccine in adolescents 12 to 18 years with RD and immunosuppressive treatment compared with a healthy control group.
Methods
Adolescents from 12 to 18 years with RD followed at Hospital La Paz in Madrid (
n
= 40) receiving the BNT162b2 mRNA vaccination were assessed 3 weeks after complete vaccination. Healthy adolescents served as controls (
n
= 24). Humoral response was measured by IgG antiSpike antibodies, and cellular response by the quantity of IFN-γ and IL-2 present in whole blood stimulated with SARS-CoV-2 Spike and M proteins.
Results
There were no differences in spike-specific humoral or cellular response between groups (median IFN-γ response to S specific protein; 528.80 pg/ml in controls vs. 398.44 in RD patients, p 0.78, and median IL-2 response in controls: 635.68 pg/ml vs. 497.30 in RD patients, p 0.22. The most frequent diagnosis was juvenile idiopathic arthritis (26/40, 65%) followed by Lupus (6/40, 15%). 60% of cases (23/40) received TNF inhibitors and 35% (14/40) methotrexate. 40% of patients (26/64) had previous SARS-CoV-2 infection, 9 in the control group and 17 in the RD patients without differences. Of note, 70% of infections were asymptomatic. A higher IFN-γ production was found in COVID-19 recovered individuals than in naive subjects in both groups (controls: median 859 pg/ml in recovered patients vs. 450 in naïve p 0.017, and RD patients: 850 in recovered vs. 278 in naïve p 0.024). No serious adverse events or flares were reported following vaccination.
Conclusions
We conclude that standard of care treatment for adolescents with RD including TNF inhibitors and methotrexate did not affect the humoral and the cellular immunity to BNT162b2 mRNA vaccination compared to a healthy control group. The previous contact with SARS-CoV-2 was the most relevant factor in the immune response.
Journal Article
Islamic Burials and Funerary Rites. Toledo as a Case-Study for the Evolution from Andalusi to Mudejar
This article will use a range of sources to show traces of continuity or breakdown among the Islamic population of Toledo from Andalusi to Mudejar times. The archaeological information from the campaigns in Toledo’s cemeteries will provide a contrast with Christian and Arabic written sources about the location of their grounds and the practical limitations accorded by Christians to burial customs. The corpus of Islamic literature includes theoretical treatises of fiq?, Islamic breviaries –one of them from Ocaña, a nearby town in the cultural zone of influence of Toledo– and the proceedings of the meetings of a sufi confraternity in Toledo (active c. 1400-1420).
Journal Article