Volume-targeted modes of modern neonatal ventilators: how stable is the delivered tidal volume?

Objective: Volume-targeted modes are designed to deliver aconstant tidal volume (Vt) at lowest possible pressure independently of changes in compliance, resistance, and leak of the respiratory system. We examined whether these volume-targeted modes respond rapidly enough to sudden changes in respiratory mechanics (e.g., selective intubation, surfactant administration, endotracheal tube kinking, de-kinking, obstruction), resulting in insufficient or excessive Vt delivery. Design and setting: Bench study of six neonatal ventilators in the volume-targeted mode simulating preterm and full-term infant settings on atest lung. Measurements and results: Breath-to-breath expiratory Vt were measured after rapid compliance, resistance, and leak changes. Under our test settings all ventilators showed important volume overshooting following rapid increase in compliance or decrease in resistance. Between one and 16 inflations were required to return to the set Vt. Some ventilators delivered inaccurate Vt under steady state condition while others showed considerable breath-to-breath Vt variability. Conclusions: We observed inaccurate Vt delivery under specific conditions as well as immediate and sometimes prolonged volume overshooting after arapid respiratory system compliance increase or resistance decrease in volume-targeted modes of modern neonatal ventilators. Similar discrepancies between the set Vt and the delivered inflations can be harmful in clinical situations, especially in newborns. Their clinical relevance needs to be clarified with safety studies in the neonatal population and we encourage manufacturers to further improve the ventilators algorithm

Safety, tolerability, and efficacy of maralixibat in adults with primary sclerosing cholangitis: Open-label pilot study

BACKGROUND: Primary sclerosing cholangitis (PSC) is frequently associated with pruritus, which significantly impairs quality of life. Maralixibat is a selective ileal bile acid transporter (IBAT) inhibitor that lowers circulating bile acid (BA) levels and reduces pruritus in cholestatic liver diseases. This is the first proof-of-concept study of IBAT inhibition in PSC. METHODS: This open-label study evaluated the safety and tolerability of maralixibat ≤10 mg/d for 14 weeks in adults with PSC. Measures of pruritus, biomarkers of BA synthesis, cholestasis, and liver function were also assessed. RESULTS: Of 27 enrolled participants, 85.2% completed treatment. Gastrointestinal treatment-emergent adverse events (TEAEs) occurred in 81.5%, with diarrhea in 51.9%. TEAEs were mostly mild or moderate (63.0%); 1 serious TEAE (cholangitis) was considered treatment related. Mean serum BA (sBA) levels decreased by 16.7% (-14.84 µmol/L; 95% CI, -27.25 to -2.43; p = 0.0043) by week 14/early termination (ET). In participants with baseline sBA levels above normal (n = 18), mean sBA decreased by 40.0% (-22.3 µmol/L, 95% CI, -40.38 to -4.3; p = 0.004) by week 14/ET. Liver enzyme elevations were not significant; however, increases of unknown clinical significance in conjugated bilirubin levels were observed. ItchRO weekly sum scores decreased from baseline to week 14/ET by 8.4% (p = 0.0495), by 12.6% (p = 0.0275) in 18 participants with pruritus at baseline, and by 70% (p = 0.0078) in 8 participants with ItchRO daily average score ≥3 at baseline. CONCLUSIONS: Maralixibat was associated with reduced sBA levels in adults with PSC. In participants with more severe baseline pruritus, pruritus improved significantly from baseline. TEAEs were mostly gastrointestinal related. These results support further investigation of IBAT inhibitors for adults with PSC-associated pruritus. ClinicalTrials.gov: NCT02061540

Evolution de la résistance aux antibiotiques des germes respiratoires à Genève entre 1989 et 2000

L'augmentation de la résistance des bactéries aux antibiotiques est désormais un problème de santé publique. Cette thèse étudie l'évolution de ces résistances chez l'enfant <16 ans. La sensibilité aux antibiotiques de 694 souches de "Streptococcus pneumoniae", 831 souches de "Haemophilus influenzae" et 246 souches de "Moraxella catarrhalis" isolés à l'Hôpital des Enfants à Genève entre 1989 et 2000. La sensibilité du "S. pneumoniae" à la pénicilline a passé de 98% à 69%, avec surtout une augmentation des souches de sensibilité intermédiaire, et à l'érythromycine de 97% à 85%. La sensibilité à l'ampicilline de "H. influenzae" reste autour de 80% alors que celle de "M. catarrhalis" a largement diminué (29% vs. 5%). L'amoxicilline/acide clavulanique et les céphalosporines de 2ème et 3ème génération restent uniformément actif sur ces deux espèces. Une surveillance continue de cette évolution est indispensable et seule une limitation de la prescription des antibiotiques, associée à une information sur leur emploi judicieux permettront d'enrayer ce phénomène

Volume-targeted modes of modern neonatal ventilators: how stable is the delivered tidal volume?

Volume-targeted modes are designed to deliver a constant tidal volume (V(t)) at lowest possible pressure independently of changes in compliance, resistance, and leak of the respiratory system. We examined whether these volume-targeted modes respond rapidly enough to sudden changes in respiratory mechanics (e.g., selective intubation, surfactant administration, endotracheal tube kinking, de-kinking, obstruction), resulting in insufficient or excessive V(t) delivery

Trends in antibiotic resistance of respiratory tract pathogens in children in Geneva, Switzerland

Bacteria increasingly resistant to antibiotics are a major treatment concern of respiratory tract pathogens in children. The aim of this study was to assess the trends of resistance of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis to several classes of antibiotics in children<16 years of age and to compare its prevalence with surrounding countries. We studied retrospectively the susceptibility of respiratory tract pathogens isolated from specimens collected from patients at the Geneva Children's Hospital between 1989 and 2004. The susceptibility of S. pneumoniae to penicillin decreased from 98% to 58% (P<0.001) within 16 years, mainly due to strains intermediately resistant (MICs 0.12-1.0 microg/ml). Also erythromycin-susceptible pneumococci decreased from 97% to 63% (P<0.001). The susceptibility of H. influenzae to amoxicillin also significantly declined (87% vs. 82%, P<0.001), and the susceptibility of M. catarrhalis to this drug almost disappeared (29% vs. 5%, P<0.001). However, in 2004 these two bacteria remained 100% susceptible to amoxicillin-clavulanic acid, second and third generation cephalosporins. Invasive H. influenzae strains were significantly more resistant to ampicillin than non-invasive strains, but no susceptibility difference between invasive and non-invasive S. pneumoniae was determined

Management of congenital fourth branchial arch anomalies: a review and analysis of published cases

BACKGROUND/PURPOSE: Congenital fourth branchial arch anomalies are uncommon entities, heretofore described only in case reports, affecting primarily children, and typically presenting as a cervical inflammatory process. The aim of the study was to collect appropriate data on the diagnosis, treatment, and outcome of this condition and to suggest guidelines for its management. METHODS: We conducted a structured review of the literature for cases explicitly identified as congenital fourth branchial arch anomalies or meeting anatomical criteria for this condition. We computed descriptive statistics and performed several post hoc 2-way comparisons of subgroups of cases. RESULTS: We located and critically evaluated 526 cases. Fourth arch anomalies were usually located on the left (94%) and generally presented as acute suppurative thyroiditis (45%) or recurrent neck abscess (42%). Barium swallow and direct laryngoscopy were the most useful diagnostic tools. Treatment options differed mainly in recurrence rates: incision and drainage, 89%; open neck surgery and tract excision, 15%; endoscopic cauterization of the sinus tract opening, 15%; and open neck surgery with partial thyroidectomy, 8%. Complications after surgery occurred primarily in children 8 years or younger. CONCLUSION: Fourth arch anomalies are more common than once thought. Treatment of these disorders with repeated incision and drainage yields high rates of recurrence; thus, complete excision of the entire fistula tract during a quiescent period appears preferable. Combining this surgery with partial thyroidectomy may further decrease recurrence rates. Complications can likely be minimized by using antibiotic treatment of acute infections or endoscopic cauterization in children 8 years or younger, and delaying open neck surgery

Multitracer Stable Isotope Quantification of Arginase and Nitric Oxide Synthase Activity in a Mouse Model of Pseudomonas Lung Infection

Cystic fibrosis airways are deficient for L-arginine, a substrate for nitric oxide synthases (NOSs) and arginases. The rationale for this study was to quantify NOS and arginase activity in the mouse lung. Anesthetized unventilated mice received a primed constant stable isotope intravenous infusion containing labeled L-arginine, ornithine, and citrulline. The isotopic enrichment of each of the infused isotopomers and its product amino acids were measured in plasma and organ homogenates using liquid chromatography-tandem mass spectrometry. The effect of infection was studied three days after direct tracheal instillation of Pseudomonas-coated agar beads. In the infusion model, lung infection resulted in a significant (28-fold) increase in NOS activity in lung but not in trachea, kidney, liver, or plasma. Absolute rates of arginase activity in solid tissues could not be calculated in this model. In an isolated lung perfusion model used for comparison increased NOS activity in infected lungs was confirmed (28.5-fold) and lung arginase activity was increased 9.7-fold. The activity of L-arginine metabolizing enzymes can be measured using stable isotope conversion in the mouse. Accumulation of L-ornithine in the whole mouse model hindered the exact quantification of arginase activity in the lung, a problem that was overcome utilizing an isolated lung perfusion model

Multitracer Stable Isotope Quantification of Arginase and Nitric Oxide Synthase Activity in a Mouse Model of Pseudomonas Lung Infection

Cystic fibrosis airways are deficient for L-arginine, a substrate for nitric oxide synthases (NOSs) and arginases. The rationale for this study was to quantify NOS and arginase activity in the mouse lung. Anesthetized unventilated mice received a primed constant stable isotope intravenous infusion containing labeled L-arginine, ornithine, and citrulline. The isotopic enrichment of each of the infused isotopomers and its product amino acids were measured in plasma and organ homogenates using liquid chromatography-tandem mass spectrometry. The effect of infection was studied three days after direct tracheal instillation of Pseudomonas-coated agar beads. In the infusion model, lung infection resulted in a significant (28-fold) increase in NOS activity in lung but not in trachea, kidney, liver, or plasma. Absolute rates of arginase activity in solid tissues could not be calculated in this model. In an isolated lung perfusion model used for comparison increased NOS activity in infected lungs was confirmed (28.5-fold) and lung arginase activity was increased 9.7-fold. The activity of L-arginine metabolizing enzymes can be measured using stable isotope conversion in the mouse. Accumulation of L-ornithine in the whole mouse model hindered the exact quantification of arginase activity in the lung, a problem that was overcome utilizing an isolated lung perfusion model.Peer Reviewe