Francisco José Cambra

New approach to osteopenia in phenylketonuric patients.

Aim: To study bone mineralization in a group of phenylketonuric patients and to search for a possible relationship between bone mineral density, dietary control, serum minerals and nutrition intake. The response to treatment with low‐dose 1.25‐(OH)2 vitamin D in patients with osteopenia was evaluated. Methods: Twenty‐eight phenylketonuric patients (age range: 10–33 y) on dietary treatment were investigated. Bone density at the lumbar spine (Dual Energy X‐ray Absorptiometry), bone formation markers (osteocalcin and bone alkaline phosphatase), serum minerals, index of dietary control and protein, vitamin D and mineral intakes were determined. Results: Of the patients studied, 78.6% had good dietary compliance (462 ± 89 μmol/L). Mean protein, vitamin D and mineral intakes met the recommended dietary allowances (RDAs). Nevertheless, 8 patients had calcium intakes lower than 1000 g/d, and a positive correlation between Z‐score and calcium (r= 0.585; p= 0.002) or phosphorus intake (r= 0.546; p= 0.005) was observed. Osteopenia was detected in 14 patients (50%). Moreover, bone alkaline phosphatase in phenylketonuric patients older than 18 y of age was significantly lower than that in controls (p > 0.0001). No correlation was found between bone mineral density, age, serum minerals, bone formation markers or index of dietary control. Treatment with 0.25 μg/d calcitriol significantly increased bone density in 6 patients.

Do adult patients with phenylketonuria improve their quality of life after introduction/resumption of a phenylalanine-restricted diet?

Aim: To evaluate the possible influence of dietary treatment on the quality of life of adult patients with PKU (phenylketonuria) following late introduction or resumption of a Phe‐restricted diet. Methods: Fifteen adult patients with classical PKU (10F, 5M; mean age: 27.5 y, range: 16.4–37.5 y) were selected for the study. These patients had either resumed a restricted diet after a period of discontinuation, or were placed on a restricted diet after late diagnosis. All of them were interviewed about their quality of life using a 24‐item questionnaire. Results: The index of dietary control was poor (median Phe: 954 μmol/L) in 8/15 patients, regular (Phe: 514 μmol/L) in 4/15 and good (Phe: 354 μmol/L) in 3/15 patients. Fifty‐three percent of patients reported that their state of health was very good, 47% described it as good, and 40% felt that their present health on‐diet was better than it had been off‐diet; 53% believed that they were calmer, quieter and less easily upset and 40% were more alert and were more able to maintain attention while on‐diet. Thirty‐three percent of the patients felt happier, and 27% felt more vital; 20% thought that they were less impulsive and aggressive, and that they were now less argumentative than before. Sixty percent of the patients felt that their quality of life had improved on‐diet compared with the situation off‐diet.

Is there a relationship between plasma phenylalanine and cholesterol in phenylketonuric patients under dietary treatment

OBJECTIVES To study the lipid profile in a group of treated phenylketonuric patients (PKU; n = 61) compared with a group of inborn error of intermediary metabolism patients (IEM; n = 22), a group of hyperphenylalaninemic children (HPA; n = 37), and a control group without dietary restriction (n = 41). DESIGN AND METHODS Phenylalanine was analyzed by ion exchange chromatography and triglycerides, cholesterol and HDL were determined by standard procedures with the Cobas Integra analyzer. RESULTS Serum total cholesterol concentrations were significantly lower in PKU patients compared with IEM patients (whose cholesterol daily intake was similar to those of PKU patients), HPA children and the control group. A negative correlation was observed between cholesterol and phenylalanine concentrations in the PKU patients. CONCLUSIONS Our findings support the hypothesis of a relationship between high plasma phenylalanine levels and an inhibition of cholesterogenesis, although the low cholesterol intake of the special diets may also decrease serum cholesterol values.

Glutamine effects on heat shock protein 70 and interleukines 6 and 10: Randomized trial of glutamine supplementation versus standard parenteral nutrition in critically ill children.

BACKGROUND & AIMS To determine whether glutamine (Gln) supplementation would have a role modifying both the oxidative stress and the inflammatory response of critically ill children. METHODS Prospective, randomized, double-blind, interventional clinical trial. Selection criteria were children requiring parenteral nutrition for at least 5 days diagnosed with severe sepsis or post major surgery. Patients were randomly assigned to standard parenteral nutrition (SPN, 49 subjects) or standard parenteral nutrition with glutamine supplementation (SPN + Gln, 49 subjects). RESULTS Glutamine levels failed to show statistical differences between groups. At day 5, patients in the SPN + Gln group had significantly higher levels of HSP-70 (heat shock protein 70) as compared with the SPN group (68.6 vs 5.4, p = 0.014). In both groups, IL-6 (interleukine 6) levels showed a remarkable descent from baseline and day 2 (SPN: 42.24 vs 9.39, p < 0.001; SPN + Gln: 35.20 vs 13.80, p < 0.001) but only the treatment group showed a statistically significant decrease between day 2 and day 5 (13.80 vs 10.55, p = 0.013). Levels of IL-10 (interleukine 10) did not vary among visits except in the SPN between baseline and day 2 (9.55 vs 5.356, p < 0.001). At the end of the study, no significant differences between groups for PICU and hospital stay were observed. No adverse events were detected in any group. CONCLUSIONS Glutamine supplementation in critically-ill children contributed to maintain high HSP-70 levels for longer. Glutamine supplementation had no influence on IL-10 and failed to show a significant reduction of IL-6 levels.

Bronchiolitis Score of Sant Joan de Déu: BROSJOD Score, validation and usefulness

To validate the bronchiolitis score of Sant Joan de Déu (BROSJOD) and to examine the previously defined scoring cutoff. Patients and Methods: Prospective, observational study. BROSJOD scoring was done by two independent physicians (at admission, 24 and 48 hr). Internal consistency of the score was assessed using Cronbachs α. To determine inter‐rater reliability, the concordance correlation coefficient estimated as an intraclass correlation coefficient (CCC) and limits of agreement estimated as the 90% total deviation index (TDI) were estimated. An expert opinion was used to classify patients according to clinical severity. A validity analysis was conducted comparing the 3‐level classification score to that expert opinion. Volume under the surface (VUS), predictive values, and probability of correct classification (PCC) were measured to assess discriminant validity. Results: About 112 patients were recruited, 62 of them (55.4%) males. Median age: 52.5 days (IQR: 32.75–115.25). The admission Cronbachs α was 0.77 (CI95%: 0.71; 0.82) and at 24 hr it was 0.65 (CI95%: 0.48; 0.7). The inter‐rater reliability analysis was: CCC at admission 0.96 (95%CI 0.94–0.97), at 24 h 0.77 (95%CI 0.65–0.86), and at 48 hr 0.94 (95%CI 0.94–0.97); TDI 90%: 1.6, 2.9, and 1.57, respectively. The discriminant validity at admission: VUS of 0.8 (95%CI 0.70–0.90), at 24 h 0.92 (95%CI 0.85–0.99), and at 48 hr 0.93 (95%CI 0.87–0.99). The predictive values and PCC values were within 38–100% depending on the level of clinical severity. Conclusion: There is a high inter‐rater reliability, showing the BROSJOD score to be reliable and valid, even when different observers apply it. Pediatr Pulmonol. 2017;52:533–539.

Adrenomedullin is a useful biomarker for the prognosis of critically ill septic children

AIM To measure midregional pro-adrenomedullin (MR-pro-ADM) in critically ill septic patients to determine its prognostic usefulness as compared with other used biomarkers in pediatric intensive care units, C-reactive protein (CRP) and procalcitonin (PCT). MATERIALS & METHODS Prospective observational study conducted on 95 patients. RESULTS Mean levels of MR-pro-ADM were significantly higher when patients needed mechanical ventilation (3.2 ± 4.3 vs 1.6 ± 2.4) and inotropes (4.4 ± 5.2 vs 1.3 ± 1.2). Receiver operating characteristic curves of mortality were higher for MR-pro-ADM (cut-off value of 2.2). This marker showed higher positive predictive prognostic value than PCT and CRP (31 vs 21.6% and 15.8%, respectively). CONCLUSION MR-pro-ADM levels are good indicators of disease severity and show better reliability than PCT and CRP for predicting in-hospital mortality.

Traumatismo craneoencefálico grave

cion de la presion endocraneal, es imprescindible para medir la presion de perfusion cerebral, que queda definida mediante la diferencia entre la presion arterial media y la PIC, y que deberia ser mayor de 60 mmHg en adolescentes y de 50 mmHg en ninos pequenos y lactantes. Aunque algunos autores admiten como suficientes presiones de perfusion menores, estas son peligrosas al poder aparecer hipoperfusion cerebral y lesiones graves, ya que por debajo de 40 mmHg existe un elevado riesgo de muerte o estado vegetativo permanente5-7. El patron de referencia es la presion medida mediante un cateter intraventricular, que ademas permite la extraccion de liquido cefalorraquideo en caso de aumento de la PIC (fig. 1). En ocasiones puede ser dificil su colocacion dado que el aumento de la PIC puede colapsar los ventriculos. Los sistemas intraparenquimatosos con transductores situados en la punta del sensor (tipo Camino®) les siguen en fiabilidad y estabilidad, y son ampliamente utilizados. Los sensores subdurales, subaracnoideos y epidurales son menos precisos y se usan poco. Las cifras normales de PIC se situan por debajo de 15 mmHg en el paciente sedado y exento de estimulos. Para realizar los calculos de la manera mas exacta, el transductor de la presion arterial se colocara a la misma altura que el orificio de Monro8-10.

ECMO: experiencia en edad pediátrica ☆

INTRODUCTION ECMO (Extracorporeal Membrane Oxygenation) provides a vital support to patients with supposed reversible respiratory and/or cardiac failure, in whom conventional support techniques have been previously unsuccessful. OBJECTIVES To determinate the criteria used in our hospital to put paediatric patients on ECMO, compare their clinical course depending on their pathology (respiratory failure, congenital heart disease or sepsis) and identify the sequelae attributable to this technique. MATERIAL AND METHOD A retrospective review of clinical records of all patients on ECMO support in our centre, excluding those presenting typically in neonatal period. RESULTS ECMO was used on 16 patients from June 2001 to January 2007, of which 50% were males. The median age was 7 months (from 21 days to 11 years). The reason for starting ECMO was respiratory failure in 11 cases (oxygenation index >40 and/or alveolar-arterial oxygen gradient >605), congenital heart disease in 2 and sepsis in 3 (due to shock unresponsive to adequate resuscitation). The median time to starting ECMO from PICU admission was 3.58 days (from 12h to 9 days). Venovenous cannulation was used initially in 8 patients, but 5 of them needed venoarterial ECMO later. The technique was used for a mean of 8 days (from 1 to 28 days). The main complication was the isolation of bacteria in different cultures (8 patients). The overall survival was 50% (6 patients with respiratory failure and both patients submitted to cardiac surgery). Extracorporeal support was withdrawn in 7 children because their clinical situation was irreversible. Another patient died seven days after successful decannulation. We have not found any serious sequel among survivors that could be attributable to this technique. CONCLUSIONS Survival among children supported with ECMO in our hospital is similar to that recorded by the ELSO in 2004, although the prognosis depends on the initial pathology. There are different criteria for starting this technique depending on the underlying diseases: respiratory index of poor prognosis in patients with respiratory failure, haemodynamic instability in those with sepsis or cardiac failure after cardiovascular surgery. We have not found any serious sequel among the survivors which could be attributable to this technique.

Large de novo deletion in chromosome 12 affecting the PAH, IGF1, ASCL1, and TRA1 genes

Phenylketonuria is one of the most common genetic diseases in humans, affecting 1 in 10,000 whites. Deletions are generally uncommon in genes in which no long highly homologous segments are present, and in phenylalanine hydroxylase (PAH) deficiency they represent only 5% of cases. We present the case of a girl affected by classical phenylketonuria who has been screened for mutations in the PAH gene. During the molecular study a large de novo deletion has detected in 12qter, including PAH, and the genes for insulin-like growth factor 1 (IGF1), human achaete-scute homolog 1 (ASCL1), and tumor rejection antigen (TRA1). The patient showed phenylketonuria, short stature, and pathological electro-oculography results in both eyes, with high affectation of the relative electrogenesis of the photoreceptor-pigment epithelium complex. She had previously been misdiagnosed as homozygous for the IVS8nt-7A-G mutation, instead of heterozygous for a mutation and a de novo deletion. As a result incorrect genetic counseling had been given. The deletion of the PAH, IGF1, and ASCL1 genes could explain the patients phenotype corresponding to a contiguous gene syndrome. We stress the relevance of polymorphic marker haplotype analysis and the importance of family study in genetic recessive diseases, such as phenylketonuria, to avoid incorrect diagnosis and genetic counseling.

Clinical, biochemical and microbiological factors associated with the prognosis of pneumococcal meningitis in children

BACKGROUND Pneumococcal meningitis (PM) has a high morbidity and mortality. The aim of the study was to evaluate what factors are related to a poor PM prognosis. METHODS Prospective observational study conducted on patients admitted to the Pediatric Intensive Care Unit in a tertiary hospital with a diagnosis of PM (January 2000 to December 2013). Clinical, biochemical and microbiological data were recorded. Variable outcome was classified into good or poor (neurological handicap or death). A multivariate logistic regression was performed based on the univariate analysis of significant data. RESULTS A total of 88 patients were included. Clinical variables statistically significant for a poor outcome were younger age (p=.008), lengthy fever (p=.016), sepsis (p=.010), lower Glasgow Score (p<.001), higher score on Pediatric Risk Mortality Score (p=0.010) and Sequential Organ Failure Assessment (SOFA) (p<.001), longer mechanical ventilation (p=.004), and inotropic support (p=.008) requirements. Statistically significant biochemical variables were higher level of C-reactive protein (p<.001) and procalcitonin (p=.014) at admission, low cerebrospinal (CSF) pleocytosis (p=.003), higher level of protein in CSF (p=.031), and severe hypoglycorrhachia (p=.002). In multivariate analysis, independent indicators of poor outcome were age less than 2 years (p=.011), high score on SOFA (p=.030), low Glasgow Score (p=.042), and severe hypoglycorrhachia (p=.009). CONCLUSIONS Patients younger than 2 years of age, with depressed consciousness at admission, especially when longer mechanical ventilation is required, are at high risk of a poor outcome.