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T cell development and selection are coordinated in the thymus by a specialized niche of diverse stromal populations1-3. Although much progress has been made over the years in identifying the functions of the different cell types of the thymic stromal compartment, there is no comprehensive characterization of their diversity and heterogeneity. Here we combined massively parallel single-cell RNA-sequencing4,5, spatial mapping, chromatin profiling and gene targeting to characterize de novo the entire stromal compartment of the mouse thymus. We identified dozens of cell states, with thymic epithelial cells (TECs) showing the highest degree of heterogeneity. Our analysis highlights four major medullary TEC (mTEC I-IV) populations, with distinct molecular functions, epigenetic landscapes and lineage regulators. Specifically, mTEC IV constitutes a new and highly divergent TEC lineage with molecular characteristics of the gut chemosensory epithelial tuft cells. Mice deficient in Pou2f3, a master regulator of tuft cells, have complete and specific depletion of mTEC IV cells, which results in increased levels of thymus-resident type-2 innate lymphoid cells. Overall, our study provides a comprehensive characterization of the thymic stroma and identifies a new tuft-like TEC population, which is critical for shaping the immune niche in the thymus.
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Células Epiteliais/citologia , Células Epiteliais/metabolismo , Interleucina-17/metabolismo , Interleucinas/metabolismo , Análise de Célula Única , Timo/citologia , Timo/imunologia , Animais , Epigênese Genética , Células Epiteliais/imunologia , Feminino , Humanos , Interleucina-17/biossíntese , Interleucinas/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Modelos Moleculares , Fatores de Transcrição/biossíntese , Fatores de Transcrição/deficiência , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteína AIRERESUMO
On average, arterial oxygen saturation measured by pulse oximetry (SpO2) is higher in hypoxemia than the true oxygen saturation measured invasively (SaO2), thereby increasing the risk of occult hypoxemia. In the current article, measurements of SpO2 on 17 cyanotic newborns were performed by means of a Nellcor pulse oximeter (POx), based on light with two wavelengths in the red and infrared regions (660 and 900 nm), and by means of a novel POx, based on two wavelengths in the infrared region (761 and 820 nm). The SpO2 readings from the two POxs showed higher values than the invasive SaO2 readings, and the disparity increased with decreasing SaO2. SpO2 measured using the two infrared wavelengths showed better correlation with SaO2 than SpO2 measured using the red and infrared wavelengths. After appropriate calibration, the standard deviation of the individual SpO2-SaO2 differences for the two-infrared POx was smaller (3.6%) than that for the red and infrared POx (6.5%, p < 0.05). The overestimation of SpO2 readings in hypoxemia was explained by the increase in hypoxemia of the optical pathlengths-ratio between the two wavelengths. The two-infrared POx can reduce the overestimation of SpO2 measurement in hypoxemia and the consequent risk of occult hypoxemia, owing to its smaller increase in pathlengths-ratio in hypoxemia.
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Oximetria , Saturação de Oxigênio , Recém-Nascido , Humanos , Hipóxia , Oxigênio , CalibragemRESUMO
OBJECTIVES: The European League Against Rheumatism and American College of Rheumatology 2019 (EULAR/ACR-19) criteria for the diagnosis of SLE were recently published, with the stated goal of maintaining the level of sensitivity and raising the level of specificity for classification of SLE in adults. The aim of this study is to examine their application to juvenile SLE (jSLE) patients. METHODS: In this multicentre study the charts of jSLE patients from three tertiary medical centres were reviewed and compared with patients with non-jSLE diagnosis. Paediatric rheumatologists, blinded to the original diagnosis, reviewed and diagnosed all cases. Paediatric patients' clinical and laboratory data were retrospectively extracted and then examined with regard to how they met the new and old criteria. RESULTS: Included were 225 patients (112 jSLE, 113 non-SLE). When applied to juvenile SLE classification, the sensitivity of the new EULAR/ACR-19 criteria was 0.96 (95% CI: 0.9, 0.99) and the specificity was 0.89 (95% CI: 0.82, 0.94). These were comparable to the SLICC criteria. The sensitivity of the EULAR/ACR-19 criteria improves over time and was 0.83 12 months following disease onset, reaching 0.96 after longer than 24 months. CONCLUSION: Among a cohort of jSLE patients, sensitivity of the new EULAR/ACR-19 criteria was found to be high and specificity may have improved slightly compared with the SLICC-12 criteria. We support the use of the new classification criteria for paediatric patients in future jSLE studies, but it should be noted that its specificity is lower than for adults.
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Lúpus Eritematoso Sistêmico/diagnóstico , Adolescente , Criança , Feminino , Humanos , Masculino , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: We investigated the risk of kidney injury among adolescents with and without a congenital single functioning kidney (SFK). METHODS: This retrospective study is based on a medical evaluation database of 17-year-old Israeli conscripts, born during 1989-1999. Those with congenital SFK diagnosis, verified by a pediatric nephrologist's review of the original military medical committee classifications, were compared to the rest of the cohort. Kidney injury (KI) was defined as proteinuria, high blood pressure (BP), or estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73 m2 prior to army recruitment. Risk factors for KI were examined using logistic regression. RESULTS: Of 979,630 screened candidates, 353 were diagnosed with SFK. The yearly incidence of SFK gradually increased in the first years of the study, reaching a plateau in 1995 (5.5 ± 1.2/10,000 births/year). The male to female ratio was 2.7:1. Concomitant genital malformations were documented in 5.5% of those with SFK. KI was more prevalent in the SFK than the control group (42.2% vs. 23.5%, p < 0.001). All three components of KI were more common in the SFK than the control group: high BP (31.7% vs. 23.1%, p < 0.001), proteinuria (18.2% vs. 0.4%, p < 0.001), and eGFR <90 ml/min/1.73m2 (12.0% vs 0.1%, p < 0.001). Multivariate analysis of the SFK group revealed associations of higher mean BMI, male sex, and smaller ultrasonographic kidney length with KI. CONCLUSIONS: This large population-based study documents a significant risk for KI among adolescents with SFK. Obesity represents a major modifiable risk factor for KI, implicating the need for closer follow-up in this group during childhood.
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Rim Único , Adolescente , Feminino , Taxa de Filtração Glomerular , Humanos , Hipertensão , Rim , Masculino , Prognóstico , Proteinúria/epidemiologia , Estudos Retrospectivos , Rim Único/epidemiologiaRESUMO
Acute urinary tract infection (UTI) is the most common bacterial infection in childhood. Although hyponatremia was described in ~ 2/3 of these children, its clinical significance is still unclear. Herein, we evaluated the prevalence and clinical implications of hyponatremia in children hospitalized with a UTI. Medical records of previously healthy children hospitalized between January 2011 and December 2016 with UTI were retrospectively reviewed. Patients (median age 5.5 months) were divided into two groups according to their sodium levels: normonatremia (Na ≥ 135 mEq/L) and hyponatremia (Na < 135 mEq/L). Hyponatremia diagnosed on admission was found in 114/219 children (49%). Hyponatremic patients experienced a more severe disease manifested by a longer hospital stay (3.8 vs 3.4 days, p = 0.003), a higher prevalence of abnormal findings on renal ultrasound (10 vs 2, p = 0.01), higher C-reactive protein (CRP) levels (8.6 vs 3.4 mg/dl, p = <0.001), and a negative correlation between sodium levels and CRP (r = - 0.38, p < 0.001).Conclusion:Hyponatremia occurs frequently in children hospitalized with UTI and is associated with elevated inflammatory markers and a more severe disease course. What is Known: ⢠Hyponatremia, one of the most common electrolyte abnormalities, occurs in approximately 1/3 of hospitalized children and in 2/3 of children with pyelonephritis. ⢠In certain cases of various medical conditions, hyponatremia has been shown to correlate with disease severity. What is New: ⢠Hyponatremia in hospitalized children with UTI correlates with elevated inflammatory markers and a more severe disease course.
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Hiponatremia , Pielonefrite , Infecções Urinárias , Criança , Humanos , Hiponatremia/epidemiologia , Hiponatremia/etiologia , Lactente , Estudos Retrospectivos , Sódio , Infecções Urinárias/complicações , Infecções Urinárias/epidemiologiaRESUMO
Familial Mediterranean Fever (FMF), the most common monogenic inflammatory disease, is mainly treated by oral Colchicine. However, 5% of patients are considered non-responders and, therefore, candidates for biologic therapy. Intravenous (IV) Colchicine treatment has been shown to be effective and safe in adult patients. The objective of this study was to evaluate the safety of IV Colchicine for pediatric FMF patients in our hospital, refractory to oral Colchicine, by reviewing their medical records. Inclusion criteria were all patients with FMF who commenced treatment with IV Colchicine before the age of 18 years, and received at least 6 months of IV therapy. The patients completed questionnaires to assess the efficacy of the treatment. Between 2004 and 2017, 7 pediatric FMF patients receiving maximal oral Colchicine doses and deemed non-responders were treated with weekly IV Colchicine, including 38 cumulative patient years of follow-up data (a full blood count, renal and liver function tests). All patients were homozygous for the M694V genotype. Long-term follow-up showed normal laboratory results with no Colchicine-related hospital admissions or toxicity. Global health assessment and the number of disease-free days have significantly improved (P < 0.05). Prolonged IV Colchicine use is described in pediatric FMF patients for the first time, with an excellent safety profile in our population, and decrease in intensity and frequency of attacks. In the biological era, IV Colchicine, although not leading to complete remission, may be considered a second-line option in countries where anti-interleukin 1 blockers are not available, or as a third-line option in case of failure to respond to biologics.
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Colchicina/administração & dosagem , Febre Familiar do Mediterrâneo/tratamento farmacológico , Moduladores de Tubulina/administração & dosagem , Administração Intravenosa , Administração Oral , Adolescente , Criança , Pré-Escolar , Colchicina/uso terapêutico , Resistência a Medicamentos , Feminino , Humanos , Masculino , Resultado do Tratamento , Moduladores de Tubulina/uso terapêuticoRESUMO
BACKGROUND: Decreased production of erythropoietin (EPO) is a major cause of anemia associated with chronic kidney disease (CKD). Treatment with recombinant human EPO (rHuEPO) improves patients' quality of life and survival; however, there is a marked variability in response to rHuEPO. At present, no available laboratory test is capable of evaluating responsiveness to EPO treatment. The aim of the present study was to use an in vitro bioassay to estimate the effect of uremic environment on EPO-dependent erythroid cell proliferation. METHODS: EPO-dependent human erythroleukemia cells (UT-7) were incubated with exogenous EPO (2 u/ml) and sera obtained from 60 pediatric patients (aged 1-23 years). Three groups were studied: (1) 12 children on dialysis (4 peritoneal, 8 hemodialysis); (2) 28 patients with CKD 1-5 (not on dialysis), and (3) 20 healthy children. RESULTS: Sera from dialysis patients inhibited UT-7 cell growth compared to the CKD group and healthy controls at 48 h (p = 0.003 and p = 0.04, respectively) and 72 h of culture (p = 0.02 and p = 0.07, respectively). In 18 patients treated with rHuEPO, a significant inverse correlation was found between the EPO resistance index and cell proliferation at 48 h (p = 0.007, r = - 0.63) and 72 h (p = 0.03, r = - 0.52). CONCLUSIONS: Our findings support the presence of erythropoiesis inhibitory substances in uremic sera. EPO/EPO-R-dependent mechanisms may play a role in inhibiting erythropoiesis. The in vitro bioassay described herein may serve as an indicator of rHuEPO responsiveness which may encourage further investigation of underlying mechanisms of EPO resistance.
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Anemia/tratamento farmacológico , Bioensaio , Eritropoetina/farmacologia , Insuficiência Renal Crônica/sangue , Uremia/sangue , Adolescente , Adulto , Anemia/sangue , Anemia/etiologia , Linhagem Celular Tumoral , Criança , Pré-Escolar , Resistência a Medicamentos , Eritropoese/efeitos dos fármacos , Eritropoetina/uso terapêutico , Feminino , Humanos , Lactente , Masculino , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Diálise Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Resultado do Tratamento , Uremia/etiologia , Uremia/terapia , Adulto JovemRESUMO
OBJECTIVE: Because of an increased resistance of urinary pathogens to penicillin derivatives, nitrofurantoin is commonly used as an alternative in treating urinary tract infection because a wide range of both Gram negative and positive organisms are sensitive to it. The safety of the fetus after exposure to nitrofurantoin remains controversial. METHODS: We conducted a systematic review and meta-analysis to evaluate the fetal safety of nitrofurantoin. We searched Medline, EMBASE, references from published reports, and meeting abstracts for relevant studies. Articles were included in the review if they were human studies, reported pregnancy outcomes, reported the use of nitrofurantoin in the first trimester of pregnancy, and included a comparator group of unexposed pregnancies. The primary outcome was the rate of major malformations; secondary outcomes were rates of craniosynostosis, cleft lip or palate defects, cardiovascular defects, and hypoplastic left heart syndrome. RESULTS: Eight studies reporting on 91 115 exposed cases and 1 578 745 unexposed controls were included in the primary meta-analysis examining the risk of major malformation. Five cohort studies reported on 9275 exposed and 1 491 933 unexposed infants, resulting in an overall RR of 1.01 (95% CI 0.81 to 1.26); however, three case-control studies with a total of 39 268 cases of major malformations and 129 394 controls gave an overall OR of 1.22 (95% CI 1.02 to 1.45). No increased risk for cardiovascular malformations, oral cleft, or craniosynostosis was identified. For assessing risk of hypoplastic left heart syndrome, only three articles were eligible; these demonstrated an OR of 3.07 (95% CI 1.59 to 5.93). CONCLUSION: While no association was found between fetal exposure to nitrofurantoin and major malformation in cohort studies, there was a slight but significant teratogenic risk in case-control studies, which are more sensitive to adverse effects.
Objectif : Compte tenu de la résistance accrue des pathogènes urinaires aux dérivés de la pénicilline, la nitrofurantoïne est couramment utilisée à titre de solution de rechange pour la prise en charge de l'infection des voies urinaires, et ce, en raison de la vaste gamme des organismes tant Gram négatifs que Gram positifs qui y sont sensibles. L'innocuité de l'exposition du fÅtus à la nitrofurantoïne demeure controversée. Méthodes : Nous avons mené une analyse systématique et une méta-analyse afin d'évaluer l'innocuité fÅtale de la nitrofurantoïne. Nous avons mené des recherches dans Medline, EMBASE, les références de rapports publiés et des résumés de réunion en vue d'en tirer les études pertinentes. Les articles ont été inclus dans l'analyse s'il s'agissait d'études menées chez l'homme, s'ils faisaient état des issues de grossesse, s'ils traitaient de l'utilisation de nitrofurantoïne au cours du premier trimestre de grossesse et s'ils comprenaient un groupe témoin de grossesses non exposées. Le taux de malformations majeures constituait le critère d'évaluation principal; les taux de craniosynostose, de fente labiale ou palatine, d'anomalies cardiovasculaires et d'hypoplasie du cÅur gauche constituaient les critères d'évaluation secondaires. Résultats : Huit études couvrant un total de 91 115 cas exposés et de 1 578 745 témoins non exposés ont été incluses dans la méta-analyse primaire examinant le risque de malformation majeure. Cinq études de cohorte se sont penchées sur 9 275 nouveau-nés exposés et sur 1 491 933 nouveau-nés non exposés, le tout donnant lieu à un RR global de 1,01 (IC à 95 %, 0,81 - 1,26); toutefois, trois études cas-témoins s'étant penchées sur un total de 39 268 cas de malformations majeures et de 129 394 cas témoins ont donné lieu à un RC global de 1,22 (IC à 95 %, 1,02 - 1,45). Aucune hausse du risque de malformations cardiovasculaires, de fente orale ou de craniosynostose n'a été identifiée. Pour ce qui est de l'évaluation du risque d'hypoplasie du cÅur gauche, seuls trois articles étaient admissibles; ces articles ont donné lieu à un RC de 3,07 (IC à 95 %, 1,59 - 5,93). Conclusion : Bien qu'aucune association n'ait été constatée entre l'exposition du fÅtus à la nitrofurantoïne et la manifestation de malformations majeures dans le cadre d'études de cohorte, un risque léger mais significatif de tératogénicité a été constaté dans le cadre d'études cas-témoins (lesquelles sont plus sensibles aux effets indésirables).
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Anormalidades Induzidas por Medicamentos/etiologia , Anti-Infecciosos Urinários/efeitos adversos , Nitrofurantoína/efeitos adversos , Feminino , Humanos , Exposição Materna , Gravidez , Primeiro Trimestre da GravidezRESUMO
During the COVID-19 pandemic wearing face masks was mandatory. Nowadays, face masks are still encouraged indoors, especially in hospitals. People climbing stairs with masks describe unpredictable dyspnea. In this study, healthy adults climbed 5 floors with and without a mask. Various cardio-respiratory parameters were measured, including O2-saturation (O2-Sat) and end-tidal CO2(EtCO2), at baseline and on the top floor. Subjective indexes, such as Borg's scale, were evaluated. Thirty-two volunteers (16 males), median age 39 years (IQR 32.5-43), median BMI = 23.6 (IQR 21.5-25.1), with good fitness levels, participated. Comparing baseline to end-activity, median (IQR): O2-Sat change was -1.0% (-2-0) without mask, versus -3.0% (-4-0) with mask,p= 0.003; EtCO2+ 7.0 (+3.3-+9) without mask, versus +8.0 (+6-+12) with mask,p= 0.0001. Hypercarbia was seen in 5 (15.6%) participants without mask, median = 48 mmHg (IQR 47.5-51), and in 11 (34%) participants with mask, median = 50 mmHg (IQR 47-54),p< 0.001. Desaturation (O2-Sat < 95%) was seen in 5 (15.6%) participants without mask, median = 94% (IQR 93%-94%), and in 10 (31%) participants with mask, median = 91.5% (IQR 90%-93%),p= 0.06. Regression analysis demonstrated that only male sex was significantly associated with abnormal EtCO2(OR = 26.4, 95% CI = 1.9-366.4,p= 0.005). Ascent duration increased from median (IQR) of 94 s (86-100) without mask to 98 s (89-107) with mask,p< 0.001. Borg's scale of perceived exertion (range 0-10) increased from median (IQR) of 3.0 (2.5-3.87) without mask to 4.0 (3.0-4.37) with mask,p< 0.001. To conclude, during routine daily activities, such as stair-climbing, face masks cause dyspnea, and have measurable influences on ventilation, including true desaturation and hypercapnia, especially in males.
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COVID-19 , Máscaras , Humanos , Masculino , Máscaras/efeitos adversos , Máscaras/estatística & dados numéricos , Feminino , Adulto , COVID-19/prevenção & controle , Dispneia/fisiopatologia , Dispneia/etiologia , SARS-CoV-2 , Saturação de OxigênioRESUMO
Importance: Severe respiratory disease declined during the COVID-19 pandemic, partially due to decreased circulation of respiratory pathogens. However, the outcomes of children with higher risk have not been described using population-based data. Objective: To compare respiratory-related hospitalizations, intensive care unit (ICU) admissions, and mortality during the pandemic vs prepandemic, among children with medical complexity (CMC) and without medical complexity (non-CMC). Design, Setting, and Participants: This population-based repeated cross-sectional study used Canadian health administrative data of children aged younger than 18 years in community and pediatric hospitals during a pandemic period (April 1, 2020, to February 28, 2022) compared with a 3-year prepandemic period (April 1, 2017, to March 31, 2020). The pandemic period was analyzed separately for year 1 (April 1, 2020, to March 31, 2021) and year 2 (April 1, 2021, to February 28, 2022). Statistical analysis was performed from October 2022 to April 2023. Main Outcomes and Measures: Respiratory-related hospitalizations, ICU admissions, and mortality before and during the pandemic among CMC and non-CMC. Results: A total of 139â¯078 respiratory hospitalizations (29â¯461 respiratory hospitalizations for CMC and 109â¯617 for non-CMC) occurred during the study period. Among CMC, there were fewer respiratory hospitalizations in both 2020 (rate ratio [RR], 0.44 [95% CI, 0.42-0.46]) and 2021 (RR, 0.55 [95% CI, 0.51-0.62]) compared with the prepandemic period. Among non-CMC, there was an even larger relative reduction in respiratory hospitalizations in 2020 (RR, 0.18 [95% CI, 0.17-0.19]) and a similar reduction in 2021 (RR, 0.55 [95% CI, 0.54-0.56]), compared with the prepandemic period. Reductions in ICU admissions for respiratory illness followed a similar pattern for CMC (2020: RR, 0.56 [95% CI, 0.53-0.59]; 2021: RR, 0.66 [95% CI, 0.63-0.70]) and non-CMC (2020: RR, 0.22 [95% CI, 0.20-0.24]; RR, 0.65 [95% CI, 0.61-0.69]). In-hospital mortality for these conditions decreased among CMC in both 2020 (RR, 0.63 [95% CI, 0.51-0.77]) and 2021 (RR, 0.72 [95% CI, 0.59-0.87]). Conclusions and Relevance: This cross-sectional study found a substantial decrease in severe respiratory disease resulting in hospitalizations, ICU admissions, and mortality during the first 2 years of the pandemic compared with the 3 prepandemic years. These findings suggest that future evaluations of the effect of public health interventions aimed at reducing circulating respiratory pathogens during nonpandemic periods of increased respiratory illness may be warranted.
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COVID-19 , Transtornos Respiratórios , Doenças Respiratórias , Criança , Humanos , Pandemias , Estudos Transversais , COVID-19/epidemiologia , Canadá/epidemiologiaRESUMO
OBJECTIVES: Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease. Intra-articular corticosteroids joint injection (IAJI), with triamcinolone hexacetonide (TH) or triamcinolone acetonide (TA), is an effective additional treatment for oligo and polyarticular JIA. Previous studies have shown the benefits of TH over TA; however, TA is still used in many pediatric rheumatology centers. Our unit has experience with both regimens, and therefore we aimed to compare the efficacy and safety of TA versus TH for JIA patients. METHODS: Chart review of JIA patients who were randomly (based on drug availability) treated with TA or TH IAJI during 2010-2019. Primary outcomes for efficacy were defined as full recovery from arthritis one month after IAJI and a relapse rate of arthritis 3 months after IAJI. Primary outcome for safety was defined as the occurrence of adverse events (AEs) during the follow up period after IAJI. RESULTS: Overall, 292 joints of 102 JIA patients were treated (138 TA/154 TH joints). Complete recovery after one month was documented in 107 (69.6%) of TA treated joints and 96 (69.5%) of TH treated joints (P = 0.232). However, rate of relapse after 3 months was significantly higher for TA treated joints (27 (20.1%) vs. 13 (8.8%), respectively, P < 0.01). No AEs were documented except minor scars at four joint injection sites. CONCLUSION: The recovery from arthritis was similar (~ 70%) with both regimens, however relapse rate was more than double in TA as compared to TH injected joints. These findings are important due to a contemporary shortage of TH in the US market.
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Artrite Juvenil/tratamento farmacológico , Injeções Intra-Articulares , Triancinolona Acetonida/análogos & derivados , Triancinolona Acetonida/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Criança , Pré-Escolar , Feminino , Glucocorticoides/uso terapêutico , Humanos , Lactente , Masculino , RecidivaRESUMO
Introduction: Several dry-powder inhalers (DPIs) contain lactose which may be contaminated with milk proteins. Confusion exists pertaining to DPI use in patients with cow's milk protein allergy (CMPA). Methods: A computerized survey sent via e-mail to pediatric pulmonologists and allergologists. Results: A total of 77 out of 232 (33.2%) doctors replied, of whom 80.5% were pediatric pulmonologists. A total of 69 of 77 (89.6%) were specialists, 37.6% with more than 15 years of experience. The most commonly used DPIs were formoterol + budesonide and vilanterol + fluticasone. A total of 62 out of 77 (80.5%) responders knew these DPIs contained lactose. A total of 35 out of 77 (45.5%) doctors who replied did not know that DPI leaflets list CMPA as a contra-indication to DPI administration. Of these, 4 (11.4%) stated that they would instruct patients with CMPA to stop DPIs, and 7 (20%) would avoid recommending DPIs. A total of 42 out of 77 (54.5%) responders were aware of this warning, yet 13 of these 42 (30.9%) continued to recommend lactose-containing DPIs without hesitation and 18 of these 42 (42.8%) responders prescribed DPIs but considered allergy severity. Conclusions: Almost half of certified, experienced pediatric pulmonologists and allergologists were unaware of the warning to administer DPIs to patients with CMPA. Most doctors who do know of this warning still continue to prescribe these DPIs.
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Objectives: Neonatal late-onset sepsis work-up is a frequent occurrence in every neonatal department. Blood cultures are the diagnostic gold standard, however, a negative culture prior to 48-72 h is often considered insufficient to exclude sepsis. We aimed to develop a decision tree which would enable exclusion of late-onset sepsis within 24 h using clinical and laboratory variables. Study Design: Infants evaluated for late-onset sepsis during the years 2016-2019, without major malformations, in a tertiary neonatal center were eligible for inclusion. Blood cultures and clinical and laboratory data were extracted at 0 and 24 h after sepsis work-up. Infants with bacteriologically confirmed late-onset sepsis were compared to matched control infants. Univariate logistic regression identified potential risk factors. A decision tree based on Chi-square automatic interaction detection methodology was developed and validated. Results: The study cohort was divided to a development cohort (105 patients) and a validation cohort (60 patients). At 24 h after initial evaluation, the best variables to identify sepsis were C-reactive protein > 0.75 mg/dl, neutrophil-to-lymphocyte ratio > 1.5 and sick-appearance at 24 h. Use of these 3 variables together with blood culture status at 24 h, enabled identification of all infants that eventually developed sepsis through the decision tree model. Our decision tree has an area under the receiver operating characteristic curve of 0.94 (95% CI: 0.90-0.98). Conclusions: In non-sick appearing infants with a negative blood culture at 24 h and normal laboratory values, sepsis is highly unlikely and discontinuing antibiotics after 24 h is a viable option.
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BACKGROUND: Respiratory syncytial virus (RSV) bronchiolitis is the most common lower respiratory tract disorder causing hospitalization in infants. Due to decreased hospitalization rates of premature infants following Palivizumab immune prophylaxis, the proportion of infants with chronic diseases not eligible for Palivizumab has increased. AIM: To characterize infants hospitalized during 2014-2018 with RSV bronchiolitis, to compare between those with and without chronic conditions, and to identify risk factors for severe disease. METHODS: This retrospective study analyzed demographic and clinical data of patients younger than 2 years admitted with bronchiolitis during four consecutive RSV seasons. RESULTS: Of 1124 hospitalizations due to RSV bronchiolitis, 244 (22%) were in infants with chronic diseases. Although 20/1124 qualified for RSV prophylaxis, only eight received immune prophylaxis. Compared to otherwise healthy infants, children with chronic diseases had longer hospitalizations, median 4.8 days (interquartile range [IQR]: 3.4-8.3) versus 3.7 days (IQR: 2.7-5.1), p < .001; and higher pediatric intensive care unit (PICU) and readmission rates (9% vs. 4.5%, p = .007% and 3% vs. 1%, p = .055, respectively). Children with Down's syndrome comprised 2% of all hospitalizations, but 8% of PICU admissions; their median length of hospitalization was 10.7 days (IQR: 6.6-17.6). Respiratory tract malformations were present in 2% of hospitalizations, and comprised 4% of PICU admissions. CONCLUSION: Among infants admitted with RSV bronchiolitis, those with chronic diseases had longer hospitalizations and higher rates of transfer to the PICU. Children with multiple comorbidities, and especially those with Down's syndrome, are at particularly high risk for severe hospitalization and may benefit from RSV immune prophylaxis.
Assuntos
Bronquiolite , Infecções por Vírus Respiratório Sincicial , Antivirais/uso terapêutico , Bronquiolite/tratamento farmacológico , Bronquiolite/epidemiologia , Criança , Doença Crônica , Hospitalização , Humanos , Lactente , Palivizumab/uso terapêutico , Infecções por Vírus Respiratório Sincicial/complicações , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/epidemiologia , Vírus Sinciciais Respiratórios , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Hemolytic uremic syndrome (HUS) is a significant cause for complicated acute kidney injury. In Western countries, >90% of HUS are Shiga toxin Escherichia coli (STEC) associated. METHODS: This is a retrospective review of all Israeli children diagnosed with HUS in 4 major medical centers in Israel during 1999-2016. Patients were categorized into 4 HUS etiological groups according to international guidelines: I, inherited or acquired damage to the complement cascade ("atypical HUS" [aHUS]); II, infection associated ("typical" HUS - STEC associated, Pneumococcus); III, coexisting disease; IV: other and unknown causes. RESULTS: Seventy-five children with HUS were identified; the mean annual incidence was 1.5 ± 0.7 cases/106 per year. Distribution according to etiological groups was: I: 24.0%; II: 14.7%; III: 9.3%; IV: 52.0%. Group I comprised high proportions of Arabs (55.6%), children of consanguineous parents (61.0%), and hypertension. Group II included a high proportion of children with diarrhea on presentation and central nervous system involvement. Only 5 (6.6%) had proven STEC-HUS. Group IV was similar in most characteristics to group II. Logistic regression analysis revealed 3 independent factors associated with the diagnosis of aHUS: consanguinity, lack of diarrhea, and lack of leukocytosis at presentation. Receiver operating analysis curve showed an area under the curve of 0.9 (95% CI 0.82-0.98). CONCLUSIONS: HUS incidence is lower in Israel than in most countries, especially because STEC-HUS is very rare. aHUS is the largest defined etiological group; some distinctive characteristics were identified that could facilitate its diagnosis. The current classification system leaves a high rate of "unknown cause" HUS.
Assuntos
Síndrome Hemolítico-Urêmica/etiologia , Adolescente , Criança , Pré-Escolar , Infecções por Escherichia coli/complicações , Feminino , Síndrome Hemolítico-Urêmica/diagnóstico , Síndrome Hemolítico-Urêmica/epidemiologia , Humanos , Lactente , Recém-Nascido , Israel/epidemiologia , Modelos Logísticos , Masculino , Estudos Retrospectivos , Escherichia coli Shiga Toxigênica/patogenicidadeRESUMO
OBJECTIVE: No single test can accurately identify neonatal late-onset sepsis (LOS). Our aim was to use clinical evaluation with laboratory tests to rapidly assess sepsis risk. STUDY DESIGN: A retrospective case-control study was performed in a tertiary Neonatal Center during the years 2016-2019. Infants with bacteriologically confirmed LOS were compared with control infants. A clinical health evaluation score was assigned to each infant. A prediction model was developed and validated by multivariable analysis. RESULTS: The study included 145 infants, 48 with sepsis, and 97 controls. LOS was independently associated with: sick appearance (OR: 5.7, 95% CI: 1.1-29.1), C-reactive protein > 0.75 (OR: 5.4, 95% CI: 1.1-26.3), and neutrophil-to-lymphocyte ratio > 1.5 (OR: 6.7, 95% CI: 1.2-38.5). Our model had an area under the receiver operating characteristic curve of 0.92 (95% CI: 0.86-0.97). CONCLUSIONS: Clinical evaluation with neutrophil-to-lymphocyte ratio and C-reactive protein can rapidly identify LOS enabling decreased health costs and antibiotic use.
Assuntos
Sepse Neonatal , Sepse , Estudos de Casos e Controles , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Sepse Neonatal/diagnóstico , Sepse Neonatal/epidemiologia , Estudos Retrospectivos , Sepse/diagnósticoRESUMO
OBJECTIVE: Colchicine has been found to be highly effective for the treatment of familial Mediterranean fever (FMF). However, it is FDA-approved only for children older than 4 years owing to the lack of studies in younger children. Our tertiary pediatric rheumatology department routinely uses colchicine even in very young children with FMF. The aim of the study was to evaluate its safety and efficacy in children with FMF <4 years old. METHODS: The departmental database was searched for all children diagnosed with FMF between 2010-2018. Those who started treatment with colchicine before age 4 years were identified and matched by MEFV variant to children who started treatment at age 4-8 years. Drug efficacy was assessed by the improvement in the frequency and duration of attacks. Adverse events were assessed according to the Rheumatology Common Toxicity Criteria ver. 2.0. RESULTS: The cohort included 89 patients with FMF: 41 first treated before age 4 years, and 48 first treated at age 4-8 years. Rates of complete response to colchicine were 61% in the younger group and 60.4% in the older group, Corresponding rates of partial remission were 24.4% and 29.2% (pâ¯=â¯0.77). The most frequent adverse event was diarrhea, with a prevalence of 24.4% in the younger group and22. 9% in the older group respectively (pâ¯=â¯0.87). There were no significant between-group differences in other adverse events. CONCLUSION: Colchicine is equally effective and safe for use in patients with FMF under 4 years old, with no difference in response from older pediatric patients.
Assuntos
Colchicina/uso terapêutico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Distribuição por Idade , Fatores Etários , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Moduladores de Tubulina/uso terapêuticoRESUMO
OBJECTIVE: This study describes our 5-year experience treating protracted febrile myalgia syndrome (PFMS) with pulsed doses of corticosteroids. METHODS: Eight patients with PFMS who received pulse corticosteroid therapy were identified from the electronic database of a tertiary pediatric medical center (2011-2016). Their clinical and laboratory data were collected. Differences in continuous variables between hospital admission and discharge were analyzed using Wilcoxon's matched pairs test. RESULTS: There were 6 female and 2 male patients of median age 10.45 years (range 6.2-17.1) Six patients were found to be homozygous for the M694V mutation. In 4 patients, PFMS was the first-ever manifestation of familial Mediterranean fever. Pulse corticosteroid therapy was administered at a dose of 10mg/kg for 3 days. Pain was alleviated (visual analog scale score, 0) within hours of initiation of therapy, although pain flare-ups lasting for minutes to hours were still observed during hospitalization. At discharge, all patients were prescribed continuous oral corticosteroids (1-2mg/kg) with gradual tapering down over 6 weeks. CONCLUSION: Pulse corticosteroid therapy is effective in alleviating PFMS pain; however, it does not completely abort a PFMS episode.
Assuntos
Corticosteroides/uso terapêutico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Mialgia/tratamento farmacológico , Adolescente , Corticosteroides/administração & dosagem , Criança , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To assess whether prenatal treatment with betamethasone has a significant influence on cerebral maturation indices as measured by electroencephalographic (EEG) indices. STUDY DESIGN: Infants born less than 35 weeks postmenstrual age (PMA) were prospectively enrolled if their mother received a full course of bethametasone prior to delivery (study group) or not (control group); infants with major intracranial abnormalities were excluded as well as those who were sedated or needed assisted ventilation. EEG was recorded during the first 10 days of life. Interburst intervals and maximal amplitudes of theta and delta bandwidths were calculated by a signal processing software. A multivariate general linear model was used to analyze the relationship between the 2 groups and the different electrophysiologic parameters, adjusting for PMA and mode of delivery. RESULTS: Thirty-eight infants were included in the study group and 36 in the control group. Univariate analysis demonstrated a negative correlation between PMA at test and EEG indices (interburst interval and delta and theta frequencies). Multivariate analysis demonstrated a less robust correlation of PMA and EEG indices and a positive correlation of prenatal betamethasone treatment with Theta frequencies. Repeating the data analysis separately for each study group, the above results remained significant mainly in the study group. CONCLUSIONS: Our findings suggest a possible stabilization effect of corticosteroids on the central nervous system and a possible delay of the maturation of cerebral activity related to prenatal corticosteroids use. These findings may relate to a better neurodevelopmental outcome of infants treated prenatally with corticosteroids.