Hemodynamic Effects of a High-Frequency Oscillatory Ventilation Open-Lung Strategy in Critically Ill Children With Acquired or Congenital Cardiac Disease

OBJECTIVES: To study the hemodynamic consequences of an open-lung high-frequency oscillatory ventilation (HFOV) strategy in patients with an underlying cardiac anomaly with or without intracardiac shunt or primary pulmonary hypertension with severe lung injury.DESIGN: Secondary analysis of prospectively collected data.SETTING: Medical-surgical PICU.PATIENTS: Children less than 18 years old with cardiac anomalies (± intracardiac shunt) or primary pulmonary hypertension.INTERVENTIONS: None.MEASUREMENTS AND MAIN RESULTS: Data from 52 subjects were analyzed, of whom 39 of 52 with cardiac anomaly (23/39 with intracardiac shunt) and 13 of 52 with primary pulmonary hypertension. Fourteen patients were admitted postoperatively, and 26 patients were admitted with acute respiratory failure. Five subjects (9.6%) were canulated for ECMO (of whom four for worsening respiratory status). Ten patients (19.2%) died during PICU stay. Median conventional mechanical ventilation settings prior to HFOV were peak inspiratory pressure 30 cm H 2 O (27-33 cm H 2 O), positive end-expiratory pressure 8 cm H 2 O (6-10 cm H 2 O), and F io2 0.72 (0.56-0.94). After transitioning to HFOV, there was no negative effect on mean arterial blood pressure, central venous pressure, or arterial lactate. Heart rate decreased significantly over time ( p &lt; 0.0001), without group differences. The percentage of subjects receiving a fluid bolus decreased over time ( p = 0.003), especially in those with primary pulmonary hypertension ( p = 0.0155) and without intracardiac shunt ( p = 0.0328). There were no significant differences in the cumulative number of daily boluses over time. Vasoactive Infusion Score did not increase over time. Pa co2 decreased ( p &lt; 0.0002) and arterial pH significantly improved ( p &lt; 0.0001) over time in the whole cohort. Neuromuscular blocking agents were used in all subjects switched to HFOV. Daily cumulative sedative doses were unchanged, and no clinically apparent barotrauma was found.CONCLUSIONS: No negative hemodynamic consequences occurred with an individualized, physiology-based open-lung HFOV approach in patients with cardiac anomalies or primary pulmonary hypertension suffering from severe lung injury.</p

Early Neuromuscular Blockade in Moderate-to-Severe Pediatric Acute Respiratory Distress Syndrome

Objectives: The use of neuromuscular blocking agents (NMBAs) in pediatric acute respiratory distress syndrome (PARDS) is common but unsupported by efficacy data. We sought to compare the outcomes between patients with moderate-to-severe PARDS receiving continuous NMBA during the first 48 hours of endotracheal intubation (early NMBA) and those without. Design: Secondary analysis of data from the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) clinical trial, a pediatric multicenter cluster randomized trial of sedation. Setting: Thirty-one PICUs in the United States. Patients: Children 2 weeks to 17 years receiving invasive mechanical ventilation (MV) for moderate-to-severe PARDS (i.e., oxygenation index >= 8 and bilateral infiltrates on chest radiograph on days 0-1 of endotracheal intubation). Interventions: NMBA for the entire duration of days 1 and 2 after intubation. Measurements and Main Results: Among 1,182 RESTORE patients with moderate-to-severe PARDS, 196 (17%) received early NMBA for a median of 50.0% ventilator days (interquartile range, 33.3-60.7%). The propensity score model predicting the probability of receiving early NMBA included high-frequency oscillatory ventilation on days 0-2 (odds ratio [OR], 7.61; 95% CI, 4.75-12.21) and severe PARDS on days 0-1 (OR, 2.16; 95% CI, 1.50-3.12). After adjusting for risk category, early use of NMBA was associated with a longer duration of MV (hazard ratio, 0.57; 95% CI, 0.48-0.68; p < 0.0001), but not with mortality (OR, 1.62; 95% CI, 0.92-2.85; p = 0.096) compared with no early use of NMBA. Other outcomes including cognitive, functional, and physical impairment at 6 months post-PICU discharge were similar. Outcomes did not differ when comparing high versus low NMBA usage sites or when patients were stratified by baseline PaO2/FIO2 less than 150. Conclusions: Early NMBA use was associated with a longer duration of MV. This propensity score analysis underscores the need for a randomized controlled trial in pediatrics

Biological activity differences between TGF-β1 and TGF-β3 correlate with differences in the rigidity and arrangement of their component monomers

[Image: see text] TGF-β1, -β2, and -β3 are small, secreted signaling proteins. They share 71–80% sequence identity and signal through the same receptors, yet the isoform-specific null mice have distinctive phenotypes and are inviable. The replacement of the coding sequence of TGF-β1 with TGF-β3 and TGF-β3 with TGF-β1 led to only partial rescue of the mutant phenotypes, suggesting that intrinsic differences between them contribute to the requirement of each in vivo. Here, we investigated whether the previously reported differences in the flexibility of the interfacial helix and arrangement of monomers was responsible for the differences in activity by generating two chimeric proteins in which residues 54–75 in the homodimer interface were swapped. Structural analysis of these using NMR and functional analysis using a dermal fibroblast migration assay showed that swapping the interfacial region swapped both the conformational preferences and activity. Conformational and activity differences were also observed between TGF-β3 and a variant with four helix-stabilizing residues from TGF-β1, suggesting that the observed changes were due to increased helical stability and the altered conformation, as proposed. Surface plasmon resonance analysis showed that TGF-β1, TGF-β3, and variants bound the type II signaling receptor, TβRII, nearly identically, but had small differences in the dissociation rate constant for recruitment of the type I signaling receptor, TβRI. However, the latter did not correlate with conformational preference or activity. Hence, the difference in activity arises from differences in their conformations, not their manner of receptor binding, suggesting that a matrix protein that differentially binds them might determine their distinct activities

Faecal Matrix Metalloprotease-9 Is a More Sensitive Marker For Diagnosing Pouchitis Than Faecal Calprotectin – Results From a Pilot Study

Background. Potential non-invasive markers of pouchitis would have a great deal of significance within clinical practice. This study is aimed at assessing the diagnostic accuracy of faecal calprotectin and matrix metalloprotease-9 as potential markers in patients both with and without pouchitis. Patients and methods. Stool and blood samples were collected from 33 ileal pouch-anal anastomosis patients before a follow-up pouchoscopy. Biopsy samples were taken for histological purposes. The presence of cuffitis and stenosis was evaluated with an endoscopy. Calprotectin and matrix metalloprotease-9 were quantified with an enzyme-linked immunosorbent assay. Results. Pouchitis was detected in 30.3% of the patients. The levels of faecal calprotectin and matrix metalloprotease-9 increased significantly in patients with pouchitis. The sensitivity and specificity of matrix metalloprotease-9 was higher than that of faecal calprotectin. Only matrix metalloprotease-9 correlated significantly with the severity of pouchitis. Conclusions. Faecal matrix metalloprotease-9 has a high specificity in the diagnosis of pouchitis

The relationship of the neo-angiogenic marker, endoglin, with response to neoadjuvant chemotherapy in breast cancer

Endoglin (CD105) is upregulated in endothelial cells of tissues undergoing neovascularisation. A greater number of CD105-positive vessels predicts poor survival in breast cancer. We examine whether CD105 expression predicts response to neoadjuvant chemotherapy. Fifty-seven women (median age 50 years, range 29–70) received neoadjuvant chemotherapy for operable breast cancer. Immunohistochemical staining using monoclonal antibodies to CD105 and CD34 was performed on pretreatment biopsies and post-treatment surgical specimens. Individual microvessels were counted in 10 random fields at × 200 magnification. Median counts were correlated with clinical and pathological response using the Mann–Whitney U-test. Forty-five out of fifty-seven patients (79%) responded clinically, 22 (39%) responded pathologically. On pretreatment biopsies, clinical responders had significantly lower median CD105-positive vessel counts than nonresponders (median counts 5 and 9.3/high-power field (hpf), median difference=4.0/hpf, 95% CI 0.5–8.0/hpf, P=0.02). For pathological responders and nonresponders, median counts were 4.8 and 5.5/hpf (median difference –0.5/hpf, 95% CI=−2.5–2.0/hpf, P=0.77). CD34 expression (total microvessel density) did not correlate with response. Pretreatment CD105 expression predicts for clinical response to chemotherapy, with a lower initial count being favourable. Patients with high baseline new vessel counts or increased counts after conventional therapy may benefit from additional antiangiogenic therapy

Small bowel Crohn’s disease: MR enteroclysis and capsule endoscopy compared to balloon-assisted enteroscopy

New modalities are available to visualize the small bowel in patients with Crohn’s disease (CD). The aim of this study was to compare the diagnostic yield of magnetic resonance enteroclysis (MRE) and capsule endoscopy (CE) to balloon-assisted enteroscopy (BAE) in patients with suspected or established CD of the small bowel. Consecutive, consenting patients first underwent MRE followed by CE and BAE. Patients with high-grade stenosis at MRE did not undergo CE. Reference standard for small bowel CD activity was a combination of BAE and an expert panel consensus diagnosis. Analysis included 38 patients, 27 (71%) females, mean age 36 (20–74) years, with suspected (n = 20) or established (n = 18) small bowel CD: 16 (42%) were diagnosed with active CD, and 13 (34%) by MRE with suspected high-grade stenosis, who consequently did not undergo CE. The reference standard defined high-grade stenosis in 10 (26%) patients. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value of MRE and CE for small bowel CD activity were 73 and 57%, 90 and 89%, 88 and 67%, and 78 and 84%, respectively. CE was complicated by capsule retention in one patient. MRE has a higher sensitivity and PPV than CE in small bowel CD. The use of CE is considerably limited by the high prevalence of stenotic lesions in these patients

Discovery of Yttrium, Zirconium, Niobium, Technetium, and Ruthenium Isotopes

Currently, thirty-four yttrium, thirty-five zirconium, thirty-four niobium, thirty-five technetium, and thirty-eight ruthenium isotopes have been observed and the discovery of these isotopes is discussed here. For each isotope a brief synopsis of the first refereed publication, including the production and identification method, is presented.Comment: To be published in Atomic Data and Nuclear Data Table

Definitive radiotherapy and Single-Agent radiosensitizing Ifosfamide in Patients with localized, irresectable Soft Tissue Sarcoma: A retrospective analysis

<p>Abstract</p> <p>Background and Purpose</p> <p>Standard therapy for soft-tissue sarcomas remains complete resection. For primary radiotherapy local control rates of 30-45% have been reported. We analyzed retrospectively 11 cases of radiochemotherapy with single-agent ifosfamide in patients with macroscopic soft-tissue sarcomas.</p> <p>Patients and Methods</p> <p>The patients were treated in irresectable high risk situations. Radiation therapy was performed with median 60 Gy. During the first and fifth week the concomitant chemotherapy with ifosfamide was added. Two patients received trimodal therapy with additional regional hyperthermia.</p> <p>Results</p> <p>The therapy was completed in 73% of the patients. Average local control time was 91 months, median disease-free-survival/overall-survival was 8/26 months. Five-year rates for local control/disease free survival/overall survival were 70%/34%/34%. The limited prognosis is mainly caused by systemic treatment failure.</p> <p>Conclusions</p> <p>The data strongly suggest a better outcome of radiochemotherapy with ifosfamide compared to radiotherapy alone and radiotherapy in combination with other radiosensitizers.</p