Introduction In 2014 the Consensus Document produced by the Spanish Paediatric Societies (SEIP-SE... more Introduction In 2014 the Consensus Document produced by the Spanish Paediatric Societies (SEIP-SERPE-SEOP) was published to help in the diagnosis and treatment of osteoarticular infections (OAI). In 2015 the RIOPed was considered as a multidisciplinary national network for the investigation into OAI. The aim of this study was to assess the level of adaption to the recommendations established in the Consensus during one year of follow-up. Material and methods A prospective, national multicentre study was carried out in 37 hospitals between September 2015 and September 2016. The study included patients >16 years-old with a diagnosis of OAI, confirmed by microbiological isolation, or probable: septic arthritis (SA) with >40,000 white cells in synovial fluid, or osteomyelitis (OM)/spondylodiscitis (SD) with a compatible imaging test. The results were compared with those obtained in a retrospective study conducted between 2008 and 2012. Results A total of 235 cases were included, o...
Objectives We analysed the prevalence of M184V/I and/or K65R/E/N mutations archived in proviral D... more Objectives We analysed the prevalence of M184V/I and/or K65R/E/N mutations archived in proviral DNA (pDNA) in youths with perinatal HIV, virological control and who previously carried these resistance mutations in historic plasma samples. Methods We included vertically HIV-infected youths/young adults aged ≥10 years in the Madrid Cohort of HIV-1 Infected Children and Adolescents, exposed to lamivudine and/or emtricitabine, with M184V/I and/or K65R/E/N in historic plasma samples, on antiretroviral therapy (ART), virologically suppressed (HIV-1 RNA <50 copies/mL), and with available PBMCs in the Spanish HIV BioBank. Genomic DNA was extracted from PBMCs and HIV-1 RT gene was amplified and sequenced for resistance testing by Stanford HIV Resistance tool. Results Among the 225 patients under follow-up in the study cohort, 13 (5.8%) met selection criteria, and RT sequences were recovered in 12 (92.3%) of them. All but one were Spaniards, carrying subtype B, with a median age at PBMCs s...
OBJECTIVES To assess the performance of interferon-gamma release assays (IGRAs) in the differenti... more OBJECTIVES To assess the performance of interferon-gamma release assays (IGRAs) in the differential diagnosis between Mycobacterium avium complex (MAC) and tuberculosis (TB) in children affected with subacute/chronic submandibular/cervical lymphadenitis. STUDY DESIGN Multicenter observational study comparing children with microbiologically-confirmed MAC lymphadenitis from the European NontuberculouS MycoBacterial Lymphadenitis in childrEn (ENSeMBLE) study with children with TB lymphadenitis from the Spanish Network for the Study of Pediatric TB (pTBred) database. RESULTS Overall, 78 patients with MAC and 34 with TB lymphadenitis were included. Among MAC cases, 44/74 (59.5%) had positive tuberculin skin test (TST) results at the 5 mm cutoff, compared with 32/33 (97%) TB cases (p<0.001); at the 10 mm cutoff TST results were positive in 23/74 (31.1%) vs. 26/31 (83.9%), respectively (P < .001). IGRA results were positive in only 1/32 (3.1%) MAC cases who had undergone IGRA testing, compared with 21/23 (91.3%) TB cases (p<0.001). Agreement between TST and IGRA results was poor in MAC (23.3%;κ=0.017), but good in TB cases (95.6%;κ=0.646). IGRAs had a specificity of 96.9% (95%CI:84.3-99.8%), positive predictive value (PPV) of 95.4% (95%CI:78.2-99.8%), and negative predictive value (NPV) of 93.9% (95%CI:80.4-98.9%) for TB lymphadenitis. CONCLUSIONS In contrast to TST, IGRAs have high specificity, NPV and PPV for TB lymphadenitis in children with subacute/chronic lymphadenopathy, and consequently can help to discriminate between TB and MAC disease. Therefore, IGRAs are useful tools in the diagnostic work-up of children with lymphadenopathy, particularly when culture- and PCR-results are negative.
OBJECTIVES To evaluate electrocardiogram (ECG) markers to predict coronary involvement in patient... more OBJECTIVES To evaluate electrocardiogram (ECG) markers to predict coronary involvement in patients with Kawasaki disease (KD) by assessing measures of ventricular repolarization parameters on the 12-lead ECG. STUDY DESIGN This cross-sectional study included 180 Spanish and Japanese patients <14 years of age with KD, and with/without coronary involvement, from 2011 to 2016. We manually measured the Tp-Te/QT ratio and QTc interval (with Bazett's formula) in 12-lead ECG in the acute and recovery period and explored their potential association with coronary involvement. RESULTS No association was found between Tp-Te/QT ratio obtained manually in V5 and V6 leads and coronary involvement in the acute (V5:0.25 [interquartile range, IQR 0.21-0.27] vs 0.25 [IQR 0.20-0.27] P = .80, V6:0.24 [IQR 0.21-0.27] vs 0.25 [IQR 0.20-0.27] P = .86) or the recovery (V5:0.23 [IQR 0.20-0.25] vs 0.23 [IQR 0.19-0.25] P = .68, V6:0.23 [IQR 0.20-0.25] vs 0.23 [IQR 0.17-0.25] P = .50) period. By contrast, QTc in V5 and V6 was significantly lower in patients with KD and coronary involvement in the acute period (V5:378 [IQR 364-395] vs 390 [IQR 371-411]msec, P = .04; V6:377 [IQR 364-392] vs 390 [IQR 371-410]msec, P = .01). QTc interval <385 msec in lead V6 was associated with a 2.5-fold increased risk of coronary involvement (odds ratio: 2.5 [95% confidence interval 1.2; 5.3] P = .02). CONCLUSION Manually measured QTc interval may be a marker of coronary disease in the acute period of KD.
The aim of this transversal study was to describe the virological and immunological features of H... more The aim of this transversal study was to describe the virological and immunological features of HIV-infected youths transferred from pediatric to adult care units since 1997 vs. the non-transferred patients from the Madrid Cohort of HIV-infected children and adolescents in Spain. We included 106 non-transferred and 184 transferred patients under clinical follow-up in 17 public hospitals in Madrid by the end of December 2017. Virological and immunological outcomes were compared in transferred vs. non-transferred patients. ART drug resistance mutations and HIV-variants were analyzed in all subjects with available resistance pol genotypes and/or genotypic resistance profiles. Among the study cohort, 133 (72.3%) of 184 transferred and 75 (70.7%) of 106 non-transferred patients had available resistance genotypes. Most (88.9%) of transferred had ART experience at sampling. A third (33.3%) had had a triple-class experience. Acquired drug resistance (ADR) prevalence was significantly higher...
In 2016, a new interferon-gamma release assay, QuantiFERON-TB Gold Plus, was introduced. We condu... more In 2016, a new interferon-gamma release assay, QuantiFERON-TB Gold Plus, was introduced. We conducted a cross-sectional multicenter study, involving 158 children and adolescents with tuberculosis disease. The overall sensitivity of the assay was 82.9% (IQR 77.0%-88.8%), indicating that in children this test does not have higher sensitivity than previous generation interferon-gamma release assays.
Background In human immunodeficiency virus (HIV)–positive adults, low CD4 cell counts despite ful... more Background In human immunodeficiency virus (HIV)–positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children receiving suppressive ART. Methods Sixteen cohorts from the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) contributed data. Children <18 years at ART initiation, with sustained viral suppression (VS) (≤400 copies/mL) for ≥1 year were included. The prevalence of PIR (defined as World Health Organization advanced/severe immunosuppression for age) at 1 year of VS was described. Factors associated with PIR were assessed using logistic regression. Rates of acquired immunodeficiency syndrome (AIDS) or death on suppressive ART were calculated by PIR status. Results Of 2318 children included, median age was 6.4 years and 68% had advanced/severe immunosuppression at AR...
Enfermedades infecciosas y microbiologia clinica, Jan 12, 2018
Sexual intercourse is currently the main route of HIV infection in Spain. Despite decreases in ne... more Sexual intercourse is currently the main route of HIV infection in Spain. Despite decreases in new infections among women and drug users, the rate remains stable in men. The aim of this study was to assess risk behaviour and HIV awareness in a sample of young adults in Spain. A cross-sectional, observational, descriptive study was performed on a non-HIV infected sample, using a questionnaire on sexual health and HIV awareness adapted from the Spanish National Institute of Statistics. A sexual risk variable was included (high and low), which was classified as high if subjects had had three or more sexual partners and did not always use a condom in all their sexual encounters. 243 subjects were included (65.6% women) aged between 16 and 36years (mean=25.7; SD=4.1) (16-24years: 134 subjects; 25-29years: 60 subjects; over 30years: 47 subjects). Approximately 40.9% said that they used a condom in all sexual relations and 61% did not perceive any risk of infection. There were no significa...
A family with three offspring affected of Giltelman's syndrome is reported. The phenotypic va... more A family with three offspring affected of Giltelman's syndrome is reported. The phenotypic variability of this entity is emphasized. Moreover, the diagnosis criteria of the syndrome, phathophysiology, and genetics and clinical differences with Bartter's syndrome are stated.
Cirugía pediátrica : organo oficial de la Sociedad Española de Cirugía Pediátrica, 2008
The tumors of the salivary glands are infrequent in children, and parotid gland is involved in 80... more The tumors of the salivary glands are infrequent in children, and parotid gland is involved in 80% of them. When a salivary gland tumor is present, the chance of malignancy is greater in the child than in the adult. We reviewed 8 cases identified in patients aged 14 years and younger in our hospital, analyzing its antecedents, signs and symptoms, histological features, diagnosis, treatment and evolution. All the patients displayed preauricular painless, non-inflammatory and slow-growing masses to an age between 10 months and 14 years. Four or them were pleomorphic adenomas, two haemangiomas, one epidermal cysts and one myoepithelial carcinoma. We emphasize the exceptional nature of the carcinoma for its rareness and for the high degree of malignancy expressed. We made a fine needle aspiration biopsy in four cases but they were conclusive only in three. All were treated by surgical resection of the tumour except for the myoepithelial carcinoma and the recurrent pleomorphic adenoma th...
We describe a case of megacalycosis in a newborn female with a probable antenatal ultrasonographi... more We describe a case of megacalycosis in a newborn female with a probable antenatal ultrasonographic diagnosis of left multicystic dysplastic kidney. Uroradiology, ultrasonography and nuclear medicine studies were performed and diagnosis was established by excretory urogram. We have found only one previously published case of megacalycosis in which diagnosis was made during the postnatal study of antenatal hydronephrosis. Megacalycosis should be included in the differential diagnosis of prenatal hydronephrosis.
Serum levels of theophylline were determined in 54 asthmatics children aged 3,92 +/- 2,45 years, ... more Serum levels of theophylline were determined in 54 asthmatics children aged 3,92 +/- 2,45 years, who were taken oral theophylline at doses of 4,99 +/- 0,45 mg. The serum levels at 0 hours (9,22 +/- 4,90 mcg/ml) and at 2 hours (15,22 +/- 5,5 mcg/ml) showed a great variation, although they were taken similar doses. Two hours after ingestion, 34 patients showed levels between 10-20 mcg/ml in 10 children were less than 10 mcg/ml, and another 10 shown serum levels over 20 mcg/ml without symptoms. There was a good correlation between levels at 0 and 2 hours (p less than 0,002). These data may support the utility of doses employed. It is advisable knowing the individual response to theophylline for managing episodes of asthma in children, that can be made by only one determination 2 hours after ingestion.
Introduction In 2014 the Consensus Document produced by the Spanish Paediatric Societies (SEIP-SE... more Introduction In 2014 the Consensus Document produced by the Spanish Paediatric Societies (SEIP-SERPE-SEOP) was published to help in the diagnosis and treatment of osteoarticular infections (OAI). In 2015 the RIOPed was considered as a multidisciplinary national network for the investigation into OAI. The aim of this study was to assess the level of adaption to the recommendations established in the Consensus during one year of follow-up. Material and methods A prospective, national multicentre study was carried out in 37 hospitals between September 2015 and September 2016. The study included patients >16 years-old with a diagnosis of OAI, confirmed by microbiological isolation, or probable: septic arthritis (SA) with >40,000 white cells in synovial fluid, or osteomyelitis (OM)/spondylodiscitis (SD) with a compatible imaging test. The results were compared with those obtained in a retrospective study conducted between 2008 and 2012. Results A total of 235 cases were included, o...
Objectives We analysed the prevalence of M184V/I and/or K65R/E/N mutations archived in proviral D... more Objectives We analysed the prevalence of M184V/I and/or K65R/E/N mutations archived in proviral DNA (pDNA) in youths with perinatal HIV, virological control and who previously carried these resistance mutations in historic plasma samples. Methods We included vertically HIV-infected youths/young adults aged ≥10 years in the Madrid Cohort of HIV-1 Infected Children and Adolescents, exposed to lamivudine and/or emtricitabine, with M184V/I and/or K65R/E/N in historic plasma samples, on antiretroviral therapy (ART), virologically suppressed (HIV-1 RNA <50 copies/mL), and with available PBMCs in the Spanish HIV BioBank. Genomic DNA was extracted from PBMCs and HIV-1 RT gene was amplified and sequenced for resistance testing by Stanford HIV Resistance tool. Results Among the 225 patients under follow-up in the study cohort, 13 (5.8%) met selection criteria, and RT sequences were recovered in 12 (92.3%) of them. All but one were Spaniards, carrying subtype B, with a median age at PBMCs s...
OBJECTIVES To assess the performance of interferon-gamma release assays (IGRAs) in the differenti... more OBJECTIVES To assess the performance of interferon-gamma release assays (IGRAs) in the differential diagnosis between Mycobacterium avium complex (MAC) and tuberculosis (TB) in children affected with subacute/chronic submandibular/cervical lymphadenitis. STUDY DESIGN Multicenter observational study comparing children with microbiologically-confirmed MAC lymphadenitis from the European NontuberculouS MycoBacterial Lymphadenitis in childrEn (ENSeMBLE) study with children with TB lymphadenitis from the Spanish Network for the Study of Pediatric TB (pTBred) database. RESULTS Overall, 78 patients with MAC and 34 with TB lymphadenitis were included. Among MAC cases, 44/74 (59.5%) had positive tuberculin skin test (TST) results at the 5 mm cutoff, compared with 32/33 (97%) TB cases (p<0.001); at the 10 mm cutoff TST results were positive in 23/74 (31.1%) vs. 26/31 (83.9%), respectively (P < .001). IGRA results were positive in only 1/32 (3.1%) MAC cases who had undergone IGRA testing, compared with 21/23 (91.3%) TB cases (p<0.001). Agreement between TST and IGRA results was poor in MAC (23.3%;κ=0.017), but good in TB cases (95.6%;κ=0.646). IGRAs had a specificity of 96.9% (95%CI:84.3-99.8%), positive predictive value (PPV) of 95.4% (95%CI:78.2-99.8%), and negative predictive value (NPV) of 93.9% (95%CI:80.4-98.9%) for TB lymphadenitis. CONCLUSIONS In contrast to TST, IGRAs have high specificity, NPV and PPV for TB lymphadenitis in children with subacute/chronic lymphadenopathy, and consequently can help to discriminate between TB and MAC disease. Therefore, IGRAs are useful tools in the diagnostic work-up of children with lymphadenopathy, particularly when culture- and PCR-results are negative.
OBJECTIVES To evaluate electrocardiogram (ECG) markers to predict coronary involvement in patient... more OBJECTIVES To evaluate electrocardiogram (ECG) markers to predict coronary involvement in patients with Kawasaki disease (KD) by assessing measures of ventricular repolarization parameters on the 12-lead ECG. STUDY DESIGN This cross-sectional study included 180 Spanish and Japanese patients <14 years of age with KD, and with/without coronary involvement, from 2011 to 2016. We manually measured the Tp-Te/QT ratio and QTc interval (with Bazett's formula) in 12-lead ECG in the acute and recovery period and explored their potential association with coronary involvement. RESULTS No association was found between Tp-Te/QT ratio obtained manually in V5 and V6 leads and coronary involvement in the acute (V5:0.25 [interquartile range, IQR 0.21-0.27] vs 0.25 [IQR 0.20-0.27] P = .80, V6:0.24 [IQR 0.21-0.27] vs 0.25 [IQR 0.20-0.27] P = .86) or the recovery (V5:0.23 [IQR 0.20-0.25] vs 0.23 [IQR 0.19-0.25] P = .68, V6:0.23 [IQR 0.20-0.25] vs 0.23 [IQR 0.17-0.25] P = .50) period. By contrast, QTc in V5 and V6 was significantly lower in patients with KD and coronary involvement in the acute period (V5:378 [IQR 364-395] vs 390 [IQR 371-411]msec, P = .04; V6:377 [IQR 364-392] vs 390 [IQR 371-410]msec, P = .01). QTc interval <385 msec in lead V6 was associated with a 2.5-fold increased risk of coronary involvement (odds ratio: 2.5 [95% confidence interval 1.2; 5.3] P = .02). CONCLUSION Manually measured QTc interval may be a marker of coronary disease in the acute period of KD.
The aim of this transversal study was to describe the virological and immunological features of H... more The aim of this transversal study was to describe the virological and immunological features of HIV-infected youths transferred from pediatric to adult care units since 1997 vs. the non-transferred patients from the Madrid Cohort of HIV-infected children and adolescents in Spain. We included 106 non-transferred and 184 transferred patients under clinical follow-up in 17 public hospitals in Madrid by the end of December 2017. Virological and immunological outcomes were compared in transferred vs. non-transferred patients. ART drug resistance mutations and HIV-variants were analyzed in all subjects with available resistance pol genotypes and/or genotypic resistance profiles. Among the study cohort, 133 (72.3%) of 184 transferred and 75 (70.7%) of 106 non-transferred patients had available resistance genotypes. Most (88.9%) of transferred had ART experience at sampling. A third (33.3%) had had a triple-class experience. Acquired drug resistance (ADR) prevalence was significantly higher...
In 2016, a new interferon-gamma release assay, QuantiFERON-TB Gold Plus, was introduced. We condu... more In 2016, a new interferon-gamma release assay, QuantiFERON-TB Gold Plus, was introduced. We conducted a cross-sectional multicenter study, involving 158 children and adolescents with tuberculosis disease. The overall sensitivity of the assay was 82.9% (IQR 77.0%-88.8%), indicating that in children this test does not have higher sensitivity than previous generation interferon-gamma release assays.
Background In human immunodeficiency virus (HIV)–positive adults, low CD4 cell counts despite ful... more Background In human immunodeficiency virus (HIV)–positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children receiving suppressive ART. Methods Sixteen cohorts from the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) contributed data. Children <18 years at ART initiation, with sustained viral suppression (VS) (≤400 copies/mL) for ≥1 year were included. The prevalence of PIR (defined as World Health Organization advanced/severe immunosuppression for age) at 1 year of VS was described. Factors associated with PIR were assessed using logistic regression. Rates of acquired immunodeficiency syndrome (AIDS) or death on suppressive ART were calculated by PIR status. Results Of 2318 children included, median age was 6.4 years and 68% had advanced/severe immunosuppression at AR...
Enfermedades infecciosas y microbiologia clinica, Jan 12, 2018
Sexual intercourse is currently the main route of HIV infection in Spain. Despite decreases in ne... more Sexual intercourse is currently the main route of HIV infection in Spain. Despite decreases in new infections among women and drug users, the rate remains stable in men. The aim of this study was to assess risk behaviour and HIV awareness in a sample of young adults in Spain. A cross-sectional, observational, descriptive study was performed on a non-HIV infected sample, using a questionnaire on sexual health and HIV awareness adapted from the Spanish National Institute of Statistics. A sexual risk variable was included (high and low), which was classified as high if subjects had had three or more sexual partners and did not always use a condom in all their sexual encounters. 243 subjects were included (65.6% women) aged between 16 and 36years (mean=25.7; SD=4.1) (16-24years: 134 subjects; 25-29years: 60 subjects; over 30years: 47 subjects). Approximately 40.9% said that they used a condom in all sexual relations and 61% did not perceive any risk of infection. There were no significa...
A family with three offspring affected of Giltelman's syndrome is reported. The phenotypic va... more A family with three offspring affected of Giltelman's syndrome is reported. The phenotypic variability of this entity is emphasized. Moreover, the diagnosis criteria of the syndrome, phathophysiology, and genetics and clinical differences with Bartter's syndrome are stated.
Cirugía pediátrica : organo oficial de la Sociedad Española de Cirugía Pediátrica, 2008
The tumors of the salivary glands are infrequent in children, and parotid gland is involved in 80... more The tumors of the salivary glands are infrequent in children, and parotid gland is involved in 80% of them. When a salivary gland tumor is present, the chance of malignancy is greater in the child than in the adult. We reviewed 8 cases identified in patients aged 14 years and younger in our hospital, analyzing its antecedents, signs and symptoms, histological features, diagnosis, treatment and evolution. All the patients displayed preauricular painless, non-inflammatory and slow-growing masses to an age between 10 months and 14 years. Four or them were pleomorphic adenomas, two haemangiomas, one epidermal cysts and one myoepithelial carcinoma. We emphasize the exceptional nature of the carcinoma for its rareness and for the high degree of malignancy expressed. We made a fine needle aspiration biopsy in four cases but they were conclusive only in three. All were treated by surgical resection of the tumour except for the myoepithelial carcinoma and the recurrent pleomorphic adenoma th...
We describe a case of megacalycosis in a newborn female with a probable antenatal ultrasonographi... more We describe a case of megacalycosis in a newborn female with a probable antenatal ultrasonographic diagnosis of left multicystic dysplastic kidney. Uroradiology, ultrasonography and nuclear medicine studies were performed and diagnosis was established by excretory urogram. We have found only one previously published case of megacalycosis in which diagnosis was made during the postnatal study of antenatal hydronephrosis. Megacalycosis should be included in the differential diagnosis of prenatal hydronephrosis.
Serum levels of theophylline were determined in 54 asthmatics children aged 3,92 +/- 2,45 years, ... more Serum levels of theophylline were determined in 54 asthmatics children aged 3,92 +/- 2,45 years, who were taken oral theophylline at doses of 4,99 +/- 0,45 mg. The serum levels at 0 hours (9,22 +/- 4,90 mcg/ml) and at 2 hours (15,22 +/- 5,5 mcg/ml) showed a great variation, although they were taken similar doses. Two hours after ingestion, 34 patients showed levels between 10-20 mcg/ml in 10 children were less than 10 mcg/ml, and another 10 shown serum levels over 20 mcg/ml without symptoms. There was a good correlation between levels at 0 and 2 hours (p less than 0,002). These data may support the utility of doses employed. It is advisable knowing the individual response to theophylline for managing episodes of asthma in children, that can be made by only one determination 2 hours after ingestion.
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