Risk factors for intensive care admission in children with severe acute asthma in the Netherlands:a prospective multicentre study

Rationale: Severe acute asthma (SAA) can be fatal, but is often preventable. We previously observed in a retrospective cohort study, a three-fold increase in SAA paediatric intensive care (PICU) admissions between 2003 and 2013 in the Netherlands, with a significant increase during those years of numbers of children without treatment of inhaled corticosteroids (ICS). Objectives: To determine whether steroid-naïve children are at higher risk of PICU admission among those hospitalised for SAA. Furthermore, we included the secondary risk factors tobacco smoke exposure, allergic sensitisation, previous admissions and viral infections. Methods: A prospective, nationwide multicentre study of children with SAA (2-18 years) admitted to all Dutch PICUs and four general wards between 2016 and 2018. Potential risk factors for PICU admission were assessed using logistic regression analyses. Measurements and main results: 110 PICU and 111 general ward patients were included. The proportion of steroid-naïve children did not differ significantly between PICU and ward patients. PICU children were significantly older and more exposed to tobacco smoke, with symptoms >1 week prior to admission. Viral susceptibility was not a significant risk factor for PICU admission. Conclusions: Children with SAA admitted to a PICU were comparable to those admitted to a general ward with respect to ICS treatment prior to admission. Preventable risk factors for PICU admission were >7 days of symptoms without adjustment of therapy and exposure to tobacco smoke. Physicians who treat children with asthma must be aware of these risk factors

New Insight in Loss of Gut Barrier during Major Non-Abdominal Surgery

PG - e3954 AB - BACKGROUND: Gut barrier loss has been implicated as a critical event in the occurrence of postoperative complications. We aimed to study the development of gut barrier loss in patients undergoing major non-abdominal surgery. METHODOLOGY/PRINCIPAL FINDINGS: Twenty consecutive children undergoing spinal fusion surgery were included. This kind of surgery is characterized by long operation time, significant blood loss, prolonged systemic hypotension, without directly leading to compromise of the intestines by intestinal manipulation or use of extracorporeal circulation. Blood was collected preoperatively, every two hours during surgery and 2, 4, 15 and 24 hours postoperatively. Gut mucosal barrier was assessed by plasma markers for enterocyte damage (I-FABP, I-BABP) and urinary presence of tight junction protein claudin-3. Intestinal mucosal perfusion was measured by gastric tonometry (P(r)CO2, P(r-a)CO2-gap). Plasma concentration of I-FABP, I-BABP and urinary expression of claudin-3 increased rapidly and significantly after the onset of surgery in most children. Postoperatively, all markers decreased promptly towards baseline values together with normalisation of MAP. Plasma levels of I-FABP, I-BABP were significantly negatively correlated with MAP at (1/2) hour before blood sampling (-0.726 (p<0.001), -0.483 (P<0.001), respectively). Furthermore, circulating I-FABP correlated with gastric mucosal P(r)CO2, P(r-a)CO2-gap measured at the same time points (0.553 (p = 0.040), 0.585 (p = 0.028), respectively). CONCLUSIONS/SIGNIFICANCE: This study shows the development of gut barrier loss in children undergoing major non-abdominal surgery, which is related to preceding hypotension and mesenterial hypoperfusion. These data shed new light on the potential role of peroperative circulatory perturbation and intestinal barrier los

Influenza A-associated acute necrotising encephalopathy in a 10-year-old child

We report an otherwise healthy 10-year-old boy who was brought to the emergency department with altered mental status, vomiting, diarrhoea and fever (39.5°C), without signs of meningitis. The CT scan revealed bilateral hypodensities of the thalamus and cerebellum, with diffuse oedema and slight compression of the brainstem and a triventricular hydrocephalus. Lumbar puncture and blood examination revealed markedly elevated protein level of 2.4 g/L in cerebrospinal fluid and high serum aminotransferase, characteristic of acute necrotising encephalopathy (ANE). The PCR of the nasopharyngeal swab was influenza A positive. Because of signs of high intracranial pressure, mannitol was given, an external ventricular drain was placed and subsequently, a posterior fossa craniectomy was performed. Postoperatively, he showed signs of cerebellar mutism with emotional instability and diminished speech. Six months after presentation, he showed full recovery. This case illustrates ANE as a rare complication of influenza A infection

Gut mucosal cell damage in meningococcal sepsis in children:Relation with clinical outcome

Objective: The pathophysiological sequelae of meningococcal sepsis are mainly caused by deregulated microvasculature function, leading to impaired tissue blood flow. Because mature enterocytes are known to be susceptible to altered perfusion, we aimed to investigate: (1) the development of enterocyte damage; and (2) the relation between enterocyte damage and severity of disease and outcome in children with meningococcal sepsis. Design: Retrospective human study. Setting: Pediatric intensive care unit at a university hospital. Patients: Nineteen consecutive children with meningococcal sepsis were studied during their pediatric intensive care unit stay. Interventions: None. Measurement and Main Results: Circulating levels of intestinal fatty acid binding protein, a small cytosolic protein constitutively present in mature enterocytes and released on cell injury, were assessed. Severity of disease was represented by meningococcal-specific Rotterdam Score, generic Pediatric Risk of Mortality II score, and circulating interleukin-6. Clinical outcome was measured by length of pediatric intensive care unit stay and number of ventilator days. Highest plasma intestinal fatty acid binding protein values were measured on pediatric intensive care unit stay admission. At the time of admission, eight of 19 patients had higher intestinal fatty acid binding protein plasma levels than the upper reference limit of 30 healthy volunteers. In all survivors, intestinal fatty acid binding protein levels declined to normal values within 12 hrs after starting intensive treatment, whereas the three nonsurvivors maintained elevated intestinal fatty acid binding protein plasma levels. A significant correlation was found among intestinal fatty acid binding protein and Rotterdam Score, Pediatric Risk of Mortality II, interleukin-6 at admission (Spearman's r(2) = 0.402, p =.006; r(2) = 0.243, p = .045; r(2) = 0.687, p <.001, respectively). Next, a significant correlation was found between intestinal fatty acid binding protein and clinical outcome. Conclusions: Elevated plasma intestinal fatty acid binding protein is found in eight of 19 children with severe pediatric intensive care unit stay at the time of clinical presentation, suggesting the presence of enterocyte damage. Furthermore, prolonged enterocyte damage is found in nonsurvivors. Further studies are needed to clarify the potential role for assessment of plasma intestinal fatty acid binding protein in monitoring treatment of pediatric intensive care unit stay. (Crit Care Med 2010; 38:133-137

DNA repair mechanisms involved in gemcitabine cytotoxicity and in the interaction between gemcitabine and cisplatin

The influence of DNA repair mechanisms on the interaction between gemcitabine and cisplatin was studied using a panel of Chinese hamster ovary (CHO) cell lines each deficient in one of the following repair pathways: base excision repair (BER), nucleotide excision repair (NER), homologous recombination (HR) and non-homologous end joining (NHEJ). NER and HR are known to be involved in platinum-DNA adduct repair. Single agent experiments demonstrated that each of the repair deficient cell lines had a similar sensitivity towards gemcitabine as the parental cell lines, whereas the NER- and HR-deficient lines showed increased sensitivity towards cisplatin. Furthermore, in the parental cell lines, the administration sequence cisplatin followed by gemcitabine was synergistic, whereas the reversed schedule showed additivity and simultaneous administration revealed antagonistic cytotoxicity. In the repair deficient cell lines, using this synergistic schedule of cisplatin followed by gemcitabine, loss of synergy was observed in the NER- and HR-deficient cell lines. However, the magnitude of the effect in the NER-deficient cells was small. The sensitivity to the combination of cisplatin and gemcitabine shown by the BER- and NHEJ-deficient cell lines did not differ significantly from that of the parental cell line. Cellular accumulation of platinum as well as the formation of GG- and AG-intrastrand adducts in the parental line and in the HR-deficient line were not affected by gemcitabine. In conclusion, our results indicate that BER, NER, HR, and NHEJ are most likely incapable of modulating the cytotoxicity of gemcitabine, and that HR is involved in the synergistic interaction between cisplatin and gemcitabine in our cell system

Obstructive sleep apnea in obese adolescents referred for bariatric surgery:association with metabolic and cardiovascular variables

Background: obstructive sleep apnea syndrome (OSA) is a well-described disease entity in adults, with a higher prevalence in severely obese individuals, while at the same time associated with several comorbidities independently of BMI. Literature regarding OSA in severely obese adolescents is qualitatively and quantitatively limited, possibly resulting in suboptimal diagnosis and treatment. Methods: polysomnographic, demographic, anthropometric, and comorbidity-related data were prospectively collected in 56 adolescents with morbid obesity refractory to conservative treatment who presented for surgical therapy. Differences between adolescents with no/mild (apnea–hypopnea index (AHI) 0–4.9) and moderate/severe OSA (AHI ≥ 5.0) were evaluated using independent-samples t, chi-square or Fisher's exact tests. Multivariable linear regression analysis was performed to evaluate the association of several variables with AHI, corrected for BMI z-score. Results: of the 53 included subjects, 48 (90.6%) showed some degree of sleep disordered breathing and 20 (37.7%) had moderate/severe OSA. Patients with moderate/severe OSA had on average a higher neck circumference (42.4 versus 40.1 cm, p = 0.008), higher BMI z-score (3.7 versus 3.4, p = 0.003), higher plasma triglyceride level (2.2 versus 1.5 mmol/L, p = 0.012), and lower IGF (29.6 versus 40.2 mmol/L, p = 0.010) than those with no/mild OSA. BMI z-score and plasma triglyceride levels were independently related to AHI. Conclusions: OSA is highly prevalent amongst morbidly obese adolescents and is strongly associated with BMI z-score. Elevated plasma triglyceride levels are associated with AHI, independent of BMI z-score

Burden of respiratory syncytial virus bronchiolitis on the Dutch pediatric intensive care units

Respiratory syncytial virus (RSV) bronchiolitis causes substantial morbidity and mortality in young children, but insight into the burden of RSV bronchiolitis on pediatric intensive care units (PICUs) is limited. We aimed to determine the burden of RSV bronchiolitis on the PICUs in the Netherlands. Therefore, we identified all children Conclusion: The burden of severe RSV bronchiolitis on PICUs has increased in the Netherlands. Concomitantly, the use of non-invasive respiratory support, especially HFNC, has increased. What is Known: center dot RSV bronchiolitis is a major cause of childhood morbidity and mortality and may require pediatric intensive care unit admission. center dot The field of pediatric critical care for severe bronchiolitis has changed due to increased non-invasive respiratory support options. What is New: center dot The burden of RSV bronchiolitis for the Dutch PICUs has increased. These data inform future strategic PICU resource planning and implementation of RSV preventive strategies. center dot There was a significant increase in the use of high flow nasal cannula at the PICU, but the use of invasive mechanical ventilation did not decrease

Burden of respiratory syncytial virus bronchiolitis on the Dutch pediatric intensive care units

Respiratory syncytial virus (RSV) bronchiolitis causes substantial morbidity and mortality in young children, but insight into the burden of RSV bronchiolitis on pediatric intensive care units (PICUs) is limited. We aimed to determine the burden of RSV bronchiolitis on the PICUs in the Netherlands. Therefore, we identified all children ≤ 24 months of age with RSV bronchiolitis between 2003 and 2016 from a nationwide PICU registry. Subsequently we manually checked their patient records for correct diagnosis and collected patient characteristics, additional clinical data, respiratory support modes, and outcome. In total, 2161 children were admitted to the PICU for RSV bronchiolitis. The annual number of admissions increased significantly during the study period (β 4.05, SE 1.27, p = 0.01), and this increase was mostly driven by increased admissions in children up to 3 months old. Concomitantly, non-invasive respiratory support significantly increased (β 7.71, SE 0.92, p < 0.01), in particular the use of high flow nasal cannula (HFNC) (β 6.69, SE 0.96, p < 0.01), whereas the use of invasive ventilation remained stable. Conclusion: The burden of severe RSV bronchiolitis on PICUs has increased in the Netherlands. Concomitantly, the use of non-invasive respiratory support, especially HFNC, has increased. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00431-021-04079-y