Bronchiolitis Admissions in a Lebanese Tertiary Medical Center: A 10 Years' Experience

Bronchiolitis and more specifically respiratory syncytial virus (RSV) bronchiolitis is a leading cause of global childhood morbidity and mortality. Despite the previous identification of possible risk factors associated with the severity of bronchiolitis, the data from Lebanon remains limited. We described the burden of bronchiolitis hospitalizations in children under 5 years of age in a tertiary care center in Lebanon from October 2004 to October 2014 and identified the risk factors associated with severe bronchiolitis. This was a retrospective cohort study conducted at the American University of Beirut Medical Center. Records of children younger than 5 years of age admitted with a diagnosis of bronchiolitis were reviewed. More than half the patients were RSV positive. RSV bronchiolitis was found to be significantly associated with longer hospital stay compared to children with non-RSV bronchiolitis (P = 0.007). Children exposed to smoking had an increased risk for longer hospital stay (P = 0.002) and were more likely to require ICU admission (P < 0.001) and supplemental oxygen (P = 0.045). Congenital heart disease was found to be a significant risk factor for severe bronchiolitis (P < 0.005).Conclusion: Patients with RSV bronchiolitis had a longer hospital stay compared to patients with non-RSV bronchiolitis. Exposure to smoking was associated with a more severe and complicated RSV infection. Congenital heart disease was the only risk factor significantly associated with all markers of bronchiolitis disease severity

Multisystem inflammatory syndrome in children (MIS-C) and “Near MIS-C”: A continuum?

IntroductionReports of multisystem inflammatory syndrome in children (MIS-C), following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, have been increasing worldwide, with an incidence varying significantly across studies based on the definition used for the diagnosis. At our tertiary medical center in Lebanon, we encountered several cases that presented a diagnostic challenge because they mimicked MIS-C but did not meet the US Centers for Disease Control and Prevention (CDC) definition. We decided to review these cases and describe their features in comparison with cases that met the CDC criteria of MIS-C and those that had an alternative diagnosis.MethodsThis is a retrospective chart review of subjects aged <19 years old admitted to the American University of Beirut Medical Center (AUBMC) between March 1, 2020, and May 31, 2021, with suspected or confirmed MIS-C, following documented COVID-19 infection, with sufficient or insufficient criteria for diagnosis. Subjects were classified into 3 groups: “MIS-C”, “Near MIS-C” and “Alternative Diagnosis”.ResultsA total number of 29 subjects were included in our cohort. Fever was present in all subjects. In the MIS-C group, evidence for cardiovascular system involvement was the most common feature followed by the mucocutaneous and gastrointestinal systems. In the “Near MIS-C” and “Alternative Diagnosis” group, gastrointestinal symptoms were the most common with only one patient with cardiac abnormalities and none with coagulopathy. Subjects with typical MIS-C presentation had higher inflammatory markers when compared to subjects in the other groups. Almost all the subjects had positive IgG for SARS-CoV-2. Of the 29 subjects, the Royal College of Paediatrics and Child Health (RCPCH) case definition would have identified all suspected cases without an alternative diagnosis as MIS-C, whereas the World Health Organization (WHO) and the CDC definitions would have excluded 6 and 10 subjects, respectively.ConclusionMIS-C presents a diagnostic challenge due to the nonspecific symptoms, lack of pathognomonic findings, and potentially fatal complications. More research is needed to fully understand its pathogenesis, clinical presentation spectrum, and diagnostic criteria. Based on our experience, we favor the hypothesis that MIS-C has a continuum of severity that necessitates revisiting and unifying the current definitions

Short-Lived IFN-γ Effector Responses, but Long-Lived IL-10 Memory Responses, to Malaria in an Area of Low Malaria Endemicity

Immunity to malaria is widely believed to wane in the absence of reinfection, but direct evidence for the presence or absence of durable immunological memory to malaria is limited. Here, we analysed malaria-specific CD4+ T cell responses of individuals living in an area of low malaria transmission in northern Thailand, who had had a documented clinical attack of P. falciparum and/or P. vivax in the past 6 years. CD4+ T cell effector memory (CD45RO+) IFN-γ (24 hours ex vivo restimulation) and cultured IL-10 (6 day secretion into culture supernatant) responses to malaria schizont antigens were detected only in malaria-exposed subjects and were more prominent in subjects with long-lived antibodies or memory B cells specific to malaria antigens. The number of IFN-γ-producing effector memory T cells declined significantly over the 12 months of the study, and with time since last documented malaria infection, with an estimated half life of the response of 3.3 (95% CI 1.9–10.3) years. In sharp contrast, IL-10 responses were sustained for many years after last known malaria infection with no significant decline over at least 6 years. The observations have clear implications for understanding the immunoepidemiology of naturally acquired malaria infections and for malaria vaccine development

JAK1/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies

BACKGROUND. Monogenic IFN-mediated autoinflammatory diseases present in infancy with systemic inflammation, an IFN response gene signature, inflammatory organ damage, and high mortality. We used the JAK inhibitor baricitinib, with IFN-blocking activity in vitro, to ameliorate disease. METHODS. Between October 2011 and February 2017, 10 patients with CANDLE (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures), 4 patients with SAVI (stimulator of IFN genes-associated [STING-associated] vasculopathy with onset in infancy), and 4 patients with other interferonopathies were enrolled in an expanded access program. The patients underwent dose escalation, and the benefit was assessed by reductions in daily disease symptoms and corticosteroid requirement. Quality of life, organ inflammation, changes in IFN-induced biomarkers, and safety were longitudinally assessed. RESULTS. Eighteen patients were treated for a mean duration of 3.0 years (1.5-4.9 years). The median daily symptom score decreased from 1.3 (interquartile range [IQR], 0.93-1.78) to 0.25 (IQR, 0.1-0.63) (P < 0.0001). In 14 patients receiving corticosteroids at baseline, daily prednisone doses decreased from 0.44 mg/kg/day (IQR, 0.31-1.09) to 0.11 mg/kg/day (IQR, 0.02-0.24) (P < 0.01), and 5 of 10 patients with CANDLE achieved lasting clinical remission. The patients' quality of life and height and bone mineral density Z-scores significantly improved, and their IFN biomarkers decreased. Three patients, two of whom had genetically undefined conditions, discontinued treatment because of lack of efficacy, and one CANDLE patient discontinued treatment because of BK viremia and azotemia. The most common adverse events were upper respiratory infections, gastroenteritis, and BK viruria and viremia. CONCLUSION. Upon baricitinib treatment, clinical manifestations and inflammatory and IFN biomarkers improved in patients with the monogenic interferonopathies CANDLE, SAVI, and other interferonopathies. Monitoring safety and efficacy is important in benefit-risk assessment

X-linked agammaglobulinemia (XLA) : Phenotype, diagnosis, and therapeutic challenges around the world

Background: X-linked agammaglobulinemia is an inherited immunodeficiency recognized since 1952. In spite of seven decades of experience, there is still a limited understanding of regional differences in presentation and complications. This study was designed by the Primary Immunodeficiencies Committee of the World Allergy Organization to better understand regional needs, challenges and unique patient features. Methods: A survey instrument was designed by the Primary Immunodeficiencies Committee of the World Allergy Organization to collect both structured and semi-structured data on X-linked agammaglobulinemia. The survey was sent to 54 centers around the world chosen on the basis of World Allergy Organization participation and/or registration in the European Society for Immunodeficiencies. There were 40 centers that responded, comprising 32 countries. Results: This study reports on 783 patients from 40 centers around the world. Problems with diagnosis are highlighted by the reported delays in diagnosis>24 months in 34% of patients and the lack of genetic studies in 39% of centers Two infections exhibited regional variation. Vaccine-associated paralytic poliomyelitis was seen only in countries with live polio vaccination and two centers reported mycobacteria. High rates of morbidity were reported. Acute and chronic lung diseases accounted for 41% of the deaths. Unusual complications such as inflammatory bowel disease and large granular lymphocyte disease, among others were specifically enumerated, and while individually uncommon, they were collectively seen in 20.3% of patients. These data suggest that a broad range of both inflammatory, infectious, and autoimmune conditions can occur in patients. The breadth of complications and lack of data on management subsequently appeared as a significant challenge reported by centers. Survival above 20 years of age was lowest in Africa (22%) and reached above 70% in Australia, Europe and the Americas. Centers were asked to report their challenges and responses (n = 116) emphasized the difficulties in access to immunoglobulin products (16%) and reflected the ongoing need for education of both patients and referring physicians. Conclusions: This is the largest study of patients with X-linked agammaglobulinemia and emphasizes the continued morbidity and mortality of XLA despite progress in diagnosis and treatment. It presents a world view of the successes and challenges for patients and physicians alike. A pivotal finding is the need for education of physicians regarding typical symptoms suggesting a possible diagnosis of X-linked agammaglobulinemia and sharing of best practices for the less common complications.Peer reviewe

Global respiratory syncytial virus–related infant community deaths

Background Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with >99% of mortality occurring in low- and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized. Methods The RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths <6 months occurring in the community with in-hospital. Results We studied 829 RSV-related deaths <1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred <6 months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months; IQR: 0.8−3.3) was lower than in-hospital (2.4 months; IQR: 1.5−4.0; P < .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P < 0.0001). Conclusions We observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines

The effects of the principal's leadership style on teacher motivation : a comparative study of missionary schools in Australia and Lebanon

This thesis examines the effects of principal's leadership style on teacher motivation and identifies the motivational strategies if any being used in six schools belonging to Lebanese missionary orders. Three of the schools in the study are located in Australia and three are in Lebanon. The schools are managed by clergy, most of whom have qualifications in theology but few have any qualifications in education

Effet d'un chauffage micro-ondes et conventionnel sur la thermorésistance d'une Salmonelle traitée dans un produit à basse activité d'eau. Conséquences sur la qualité du produit

We explored in this study the incidence of traditional heating (water bath) and microwave on the thermotolerance of one strain of Salmonella enterica arizonae treated in a low water activity product (aw = 0.51), the sesame cream bought from the Lebanese market. A sodium chloride solution with a higher water activity (aw = 0.99), was also been artificially contaminated by the same strain of bacteria and treated by the two way of treatment. In addition of water bath and microwave treatments, experiments, under the same thermal ramp were realized in the order to compare the kinetic incidence and the way of heating on the thermotolerance of the bacterial strain treated in the sesame cream. We further examined the influence of the microwave treatment on the quality of the sesame cream in order to build an optimization of the treatment. Three criteria have been studied: viscosity, color and the peroxide index. Thereafter, an optimization of this decontamination treatment was highlighted. For both treatments, the water activity seems to have an influence on the thermotolerance of bacteria: the decimal reduction time (D₅₉) of S. enterica, in the sodium chloride solution (aw = 0.99), is two times higher than that obtained in the sesame cream (aw = 0.49, rich in lipids). On the other hand, the Salmonella treated in the cream of sesame (aw = 0.49), rich in lipids, showed a thermotolerance stronger than that treated in the solution of NaCl (aw = 0.99). This protector effect of lipids was known and has previously been reported by many authors who conclude that the protective effect of lipids is attributable to increase the thermotolerance of bacteria. We noted that the thermotolerance of this strain decrease with the pH. The sesame cream has a pH of 5.80 at 20°C where the sodium chloride solution has a pH of 6.50 at 20°C: pH and aw contribute together to increase the thermotolerance of the bacteria in the sesame cream against the NaCl solution. Furthermore, according to our works, it would appear that the same thermal ramp made with two types of heat treatment: water bath or microwave, does not provide equivalent results in terms of destruction of S. enterica. Indeed, for the same temperature reached, microwave treatment systematically gives higher number of decimal reduction than the water bath treatment.Nous avons exploré dans la présente étude l'incidence des cinétiques de chauffage traditionnel (bain-marie) et micro-ondes sur la thermorésistance d'une souche de Salmonella enterica arizonae traitée dans un produit à faible activité d'eau (aw = 0,51), la crème de sésame achetée sur le marché libanais. Une solution de chlorure de sodium ayant une activité d'eau plus élevée (aw = 0,99), a été également contaminée artificiellement par la même souche bactérienne et traitée selon les 2 modes de traitement. En plus de ces traitements au bain-marie et aux micro-ondes, des expériences, pour une même rampe thermique, ont été effectuées dans le but de comparer l'incidence de la cinétique et du mode de chauffage sur la thermorésistance de la souche étudiée traitée dans la crème de sésame. L'influence du traitement micro-ondes sur la qualité de la crème a elle aussi été examinée en vue d'une optimisation du traitement micro-ondes. Pour cela, trois critères ont été étudiés : la viscosité, la couleur et l'indice de peroxydes. Pour les deux traitements, bain-marie et micro-ondes, l'activité de l'eau semble avoir une influence sur la thermorésistance de la bactérie : le temps de réduction décimale (D₅₉) de S. enterica, dans la solution de chlorure de sodium, est deux fois plus élevé que celui obtenu dans la crème de sésame. D'autre part, la Salmonelle traitée dans la crème de sésame (aw = 0,49), riche en lipides, présente une thermorésistance plus forte que celle traitée dans la solution de NaCl (aw = 0,99). Cet effet protecteur des lipides est connu et a été mis en évidence par plusieurs auteurs qui concluent que celui-ci a pour conséquence d'augmenter la thermorésistance des bactéries. Nous notons aussi que la thermorésistance de cette souche diminue avec le pH. En effet, la crème de sésame a un pH de 5,80 à 20°C, alors que la solution de NaCl a un pH de 6,50 à 20°C : pH et aw contribuent donc conjointement à augmenter la thermorésistance de la souche bactérienne dans la crème de sésame par rapport à la solution de NaCl. Par ailleurs, d'après nos travaux, il semblerait qu'une même rampe thermique réalisée avec deux modes de traitement thermique : bain-marie ou micro-ondes, ne donne pas de résultats équivalents en termes de destruction de S. enterica. En effet, à niveau de température atteinte égal, le traitement micro-onde donne systématiquement un nombre de réduction décimale supérieure à celle du traitement au bain-marie

Effet d'un chauffage micro-ondes et conventionnel sur la thermorésistance d'une Salmonelle traitée dans un produit à basse activité d'eau (conséquences sur la qulité du produit)

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