Quality of life of survivors of paediatric intensive care

OBJECTIVE: The mortality rate in paediatric intensive care units (PICU) has fallen over the last two decades. More advanced treatment is offered to children with life-threatening disease and there is substantial interest in knowing whether long term outcome and quality of life after intensive care are acceptable. SETTING: 12-bed paediatric and neonatal intensive care unit. INTERVENTION: Prospective follow-up study with telephone interview 1 and 2 years after discharge. METHODS: Four domains of quality of life (physical function, role function, social-emotional function and health problem) were recorded by calculating the health state classification (HSC) index. Outcome was classified good (HSC 1.0-0.7), moderate (HSC 0.69-0.3), poor (HSC 0.29-0) and very poor (HSC <0). RESULTS: 661 patients were admitted to the PICU in the year 2001 with a mortality within the unit of 3.9%. Over 2 years follow-up there were 21 additional deaths (3.2%). 574 patients could be followed up after 1 year and 464 patients after 2 years. After two years the outcome was good in 77%, moderate in 15% and poor in 8%. Patients with respiratory disease had the best outcome, similar to those admitted for neurological and medical reasons. Patients admitted for postoperative care and for cardiovascular disease had a poorer quality of life. 31% of the children had preexisting health care problems and 21% of all patients had new chronic disease after intensive care. CONCLUSION: The majority of survivors admitted to the PICU have a good outcome. The overall mortality rate doubled if assessed two years after discharge.

Oxygen-sensitive 3He-MRI in bronchiolitis obliterans after lung transplantation

Oxygen-sensitive 3He-MRI was studied for the detection of differences in intrapulmonary oxygen partial pressure (pO2) between patients with normal lung transplants and those with bronchiolitis obliterans syndrome (BOS). Using software developed in-house, oxygen-sensitive 3He-MRI datasets from patients with normal lung grafts (n = 8) and with BOS (n = 6) were evaluated quantitatively. Datasets were acqiured on a 1.5-T system using a spoiled gradient echo pulse sequence. Underlying diseases were pulmonary emphysema (n = 10 datasets) and fibrosis (n = 4). BOS status was verified by pulmonary function tests. Additionally, 3He-MRI was assessed blindedly for ventilation defects. Median intrapulmonary pO2 in patients with normal lung grafts was 146 mbar compared with 108 mbar in patients with BOS. Homogeneity of pO2 distribution was greater in normal grafts (standard deviation pO2 34 versus 43 mbar). Median oxygen decrease rate during breath hold was higher in unaffected patients (-1.75 mbar/s versus -0.38 mbar/s). Normal grafts showed fewer ventilation defects (5% versus 28%, medians). Oxygen-sensitive 3He-MRI appears capable of demonstrating differences of intrapulmonary pO2 between normal lung grafts and grafts affected by BOS. Oxygen-sensitive 3He-MRI may add helpful regional information to other diagnostic techniques for the assessment and follow-up of lung transplant recipients.

Effects of clinically used antioxidants in experimental pneumococcal meningitis

Reactive oxygen intermediates mediate brain injury in bacterial meningitis. Several antioxidant drugs are clinically available, including N-acetylcysteine (NAC), deferoxamine (DFO), and trylizad-mesylate (TLM). The present study evaluated whether these antioxidants are beneficial in a model of pneumococcal meningitis. Eleven-day-old rats were infected intracisternally with Streptococcus pneumoniae and randomized to intraperitoneal treatment every 8 h with NAC (200 mg/kg), DFO (100 mg/kg), TLM (10 mg/kg), or saline (250 microL). TLM-treated animals showed a significantly reduced mortality compared with controls (P<.03). Meningitis led to extensive cortical injury at 22+/-2.2 h after infection (median, 14. 6% of cortex; range, 0-61.1%). Injury was significantly (P<.01) reduced to 1.1% (range, 0-34.6%) by NAC, to 2.3% (range, 0-19.6%) by DFO, and to 0.2% (range, 0-36.9%) by TLM (the difference was not significant among the 3 groups). None of the drugs reduced hippocampal injury. Thus, several clinically used antioxidants reduced cortical injury in experimental pneumococcal meningitis.

Resistive polymer versus forced-air warming: comparable heat transfer and core rewarming rates in volunteers

BACKGROUND: Mild perioperative hypothermia increases the risk of several severe complications. Perioperative patient warming to preserve normothermia has thus become routine, with forced-air warming being used most often. In previous studies, various resistive warming systems have shown mixed results in comparison with forced-air. Recently, a polymer-based resistive patient warming system has been developed. We compared the efficacy of a standard forced-air warming system with the resistive polymer system in volunteers. METHODS: Eight healthy volunteers participated, each on two separate study days. Unanesthetized volunteers were cooled to a core temperature (tympanic membrane) of 34 degrees C by application of forced-air at 10 degrees C and a circulating-water mattress at 4 degrees C. Meperidine and buspirone were administered to prevent shivering. In a randomly designated order, volunteers were then rewarmed (until their core temperatures reached 36 degrees C) with one of the following active warming systems: (1) forced-air warming (Bair Hugger warming cover #300, blower #750, Arizant, Eden Prairie, MN); or (2) polymer fiber resistive warming (HotDog whole body blanket, HotDog standard controller, Augustine Biomedical, Eden Prairie, MN). The alternate system was used on the second study day. Metabolic heat production, cutaneous heat loss, and core temperature were measured. RESULTS: Metabolic heat production and cutaneous heat loss were similar with each system. After a 30-min delay, core temperature increased nearly linearly by 0.98 (95% confidence interval 0.91-1.04) degrees C/h with forced-air and by 0.92 (0.85-1.00) degrees C/h with resistive heating (P = 0.4). CONCLUSIONS: Heating efficacy and core rewarming rates were similar with full-body forced-air and full-body resistive polymer heating in healthy volunteers.

Respiratory nitric oxide and pulmonary artery pressure in children of aymara and European ancestry at high altitude

Invasive studies suggest that healthy children living at high altitude display pulmonary hypertension, but the data to support this assumption are sparse. Nitric oxide (NO) synthesized by the respiratory epithelium regulates pulmonary artery pressure, and its synthesis was reported to be increased in Aymara high-altitude dwellers. We hypothesized that pulmonary artery pressure will be lower in Aymara children than in children of European ancestry at high altitude, and that this will be related to increased respiratory NO. We therefore compared pulmonary artery pressure and exhaled NO (a marker of respiratory epithelial NO synthesis) between large groups of healthy children of Aymara (n = 200; mean +/- SD age, 9.5 +/- 3.6 years) and European ancestry (n = 77) living at high altitude (3,600 to 4,000 m). We also studied a group of European children (n = 29) living at low altitude. The systolic right ventricular to right atrial pressure gradient in the Aymara children was normal, even though significantly higher than the gradient measured in European children at low altitude (22.5 +/- 6.1 mm Hg vs 17.7 +/- 3.1 mm Hg, p < 0.001). In children of European ancestry studied at high altitude, the pressure gradient was 33% higher than in the Aymara children (30.0 +/- 5.3 mm Hg vs 22.5 +/- 6.1 mm Hg, p < 0.0001). In contrast to what was expected, exhaled NO tended to be lower in Aymara children than in European children living at the same altitude (12.4 +/- 8.8 parts per billion [ppb] vs 16.1 +/- 11.1 ppb, p = 0.06) and was not related to pulmonary artery pressure in either group. Aymara children are protected from hypoxic pulmonary hypertension at high altitude. This protection does not appear to be related to increased respiratory NO synthesis.

Prior statin use, intracranial hemorrhage, and outcome after intra-arterial thrombolysis for acute ischemic stroke

BACKGROUND AND PURPOSE: There are only limited data on whether prior statin use and/or cholesterol levels are associated with intracranial hemorrhage (ICH) and outcome after intra-arterial thrombolysis. The purpose of this study was to evaluate the association of statin pretreatment and cholesterol levels with the overall frequency of ICH, the frequency of symptomatic ICH, and clinical outcome at 3 months. METHODS: We analyzed 311 consecutive patients (mean age, 63 years; 43% women) who received intra-arterial thrombolysis. RESULTS: Statin pretreatment was present in 18%. The frequency of any ICH was 20.6% and of symptomatic ICH 4.8%. Patients with any ICH were more often taking statins (30% versus 15%, P=0.005), more often had atrial fibrillation (45% versus 30%, P=0.016), had more severe strokes (mean National Institute of Health Stroke Scale score 16.5 versus 14.7, P=0.022), and less often good collaterals (16% versus 24%, P=0.001). Patients with symptomatic ICH were more often taking statins (40% versus 15%, P=0.009) and had less often good collaterals (0% versus 24%, P<0.001). Any ICH or symptomatic ICH were not associated with cholesterol levels. After multivariate analysis, the frequency of any ICH remained independently associated with previous statin use (OR, 3.1; 95% CI, 1.53 to 6.39; P=0.004), atrial fibrillation (OR, 2.5; CI, 1.35 to 4.75; P=0.004), National Institutes of Health Stroke Scale score (OR, 1.1; CI, 1.00 to 1.10; P=0.037), and worse collaterals (OR, 1.7; CI, 1.19 to 2.42; P=0.004). There was no association of outcome with prior statin use, total cholesterol level, or low-density lipoprotein cholesterol level. CONCLUSIONS: Prior statin use, but not cholesterol levels on admission, is associated with a higher frequency of any ICH after intra-arterial thrombolysis without impact on outcome.

Resuspension of the aortic valve in acute type A dissection: long-term results

BACKGROUND AND AIM OF THE STUDY: Preservation of the aortic valve during the repair of acute type A aortic dissection (AADA) is a viable option to prevent lifelong oral anticoagulation. The study aim was to assess aortic valve function following resuspension and supracoronary ascending aortic grafting. METHODS: Among a collective of 210 consecutive patients undergoing surgery for AADA, 140 (66.7%) with resuspension of the aortic valve and supracoronary ascending graft were analyzed. Of these patients, 83 (59.3%) had a complete follow up (mean 61.2 +/- 40.8 months), with 65 of the subgroup (78.3%) being followed by computed tomography scanning and echocardiography. RESULTS: Reoperation due to severe aortic valve regurgitation was required in seven patients (10.8%). The perioperative characteristics were similar in these patients; notably, no significant difference was evident with regards to the aortic annulus diameter and the severity of regurgitation at the time of surgery. The left ventricular mass index was significantly higher in patients requiring reoperation due to aortic valve regurgitation (219.3 +/- 146.6 versus 123.9 +/- 146.6 g/m2; p <0.05). None of the patients died as a result of reoperation. CONCLUSION: The long-term functional results following resuspension of the aortic valve in AADA were very good. A close echocardiographic follow up was necessary, as reoperation of the aortic valve was required in more than 10% of the collective, with an average follow up of five years. Reoperation was mainly related to secondary dilatation of the aortic root.

Dispersal and seed limitation affect diversity and productivity of montane grasslands

So far, seed limitation as a local process, and dispersal limitation as a regional process have been largely neglected in biodiversity-ecosystem functioning research. However, these processes can influence both local plant species diversity and ecosystem processes, such as biomass production. We added seeds of 60 species from the regional species pool to grassland communities at 20 montane grassland sites in Germany. In these sites, plant species diversity ranged from 10 to 34 species m(-2) and, before manipulation, diversity was not related to aboveground biomass, which ranged from 108 to 687 g m(-2). One year after seed addition, local plant species richness had increased on average by six species m(-2) (29%) compared with control plots, and this increase was highest in grasslands with intermediate productivity. The increased diversity after adding seeds was associated with an average increase of aboveground biomass of 36 g m(-2) (14.8%) compared with control plots. Thus, our results demonstrate that a positive relationship between changes in species richness and productivity, as previously reported from experimental plant communities, also holds for natural grassland ecosystems. Our results show that local plant communities are dispersal limited and a hump-shaped model appears to be the limiting outline of the natural diversity-productivity relationship. Hence, the effects of dispersal on local diversity can substantially affect the functioning of natural ecosystems.

Thromboelastometry for the assessment of coagulation abnormalities in early and established adult sepsis: a prospective cohort study

INTRODUCTION: The inflammatory response to an invading pathogen in sepsis leads to complex alterations in hemostasis by dysregulation of procoagulant and anticoagulant factors. Recent treatment options to correct these abnormalities in patients with sepsis and organ dysfunction have yielded conflicting results. Using thromboelastometry (ROTEM(R)), we assessed the course of hemostatic alterations in patients with sepsis and related these alterations to the severity of organ dysfunction. METHODS: This prospective cohort study included 30 consecutive critically ill patients with sepsis admitted to a 30-bed multidisciplinary intensive care unit (ICU). Hemostasis was analyzed with routine clotting tests as well as thromboelastometry every 12 hours for the first 48 hours, and at discharge from the ICU. Organ dysfunction was quantified using the Sequential Organ Failure Assessment (SOFA) score. RESULTS: Simplified Acute Physiology Score II and SOFA scores at ICU admission were 52 +/- 15 and 9 +/- 4, respectively. During the ICU stay the clotting time decreased from 65 +/- 8 seconds to 57 +/- 5 seconds (P = 0.021) and clot formation time (CFT) from 97 +/- 63 seconds to 63 +/- 31 seconds (P = 0.017), whereas maximal clot firmness (MCF) increased from 62 +/- 11 mm to 67 +/- 9 mm (P = 0.035). Classification by SOFA score revealed that CFT was slower (P = 0.017) and MCF weaker (P = 0.005) in patients with more severe organ failure (SOFA >or= 10, CFT 125 +/- 76 seconds, and MCF 57 +/- 11 mm) as compared with patients who had lower SOFA scores (SOFA <10, CFT 69 +/- 27, and MCF 68 +/- 8). Along with increasing coagulation factor activity, the initially increased International Normalized Ratio (INR) and prolonged activated partial thromboplastin time (aPTT) corrected over time. CONCLUSIONS: Key variables of ROTEM(R) remained within the reference ranges during the phase of critical illness in this cohort of patients with severe sepsis and septic shock without bleeding complications. Improved organ dysfunction upon discharge from the ICU was associated with shortened coagulation time, accelerated clot formation, and increased firmness of the formed blood clot when compared with values on admission. With increased severity of illness, changes of ROTEM(R) variables were more pronounced.

Virtual implant planning in the edentulous maxilla: criteria for decision making of prosthesis design

OBJECTIVES To evaluate prosthetic parameters in the edentulous anterior maxilla for decision making between fixed and removable implant prosthesis using virtual planning software. MATERIAL AND METHODS CT- or DVT-scans of 43 patients (mean age 62 ± 8 years) with an edentulous maxilla were analyzed with the NobelGuide software. Implants (≥3.5 mm diameter, ≥10 mm length) were virtually placed in the optimal three-dimensional prosthetic position of all maxillary front teeth. Anatomical and prosthetic landmarks, including the cervical crown point (C-Point), the acrylic flange border (F-Point), and the implant-platform buccal-end (I-Point) were defined in each middle section to determine four measuring parameters: (1) acrylic flange height (FLHeight), (2) mucosal coverage (MucCov), (3) crown-Implant distance (CID) and (4) buccal prosthesis profile (ProsthProfile). Based on these parameters, all patients were assigned to one of three classes: (A) MucCov ≤ 0 mm and ProsthProfile≥45(0) allowing for fixed prosthesis, (B) MucCov = 0-5 mm and/or ProsthProfile = 30(0) -45(0) probably allowing for fixed prosthesis, and (C) MucCov ≥ 5 mm and/or ProsthProfile ≤ 30(0) where removable prosthesis is favorable. Statistical analyses included descriptive methods and non-parametric tests. RESULTS Mean values were for FLHeight 10.0 mm, MucCov 5.6 mm, CID 7.4 mm, and ProsthProfile 39.1(0) . Seventy percent of patients fulfilled class C criteria (removable), 21% class B (probably fixed), and 2% class A (fixed), while in 7% (three patients) bone volume was insufficient for implant planning. CONCLUSIONS The proposed classification and virtual planning procedure simplify the decision-making process regarding type of prosthesis and increase predictability of esthetic treatment outcomes. It was demonstrated that in the majority of cases, the space between the prosthetic crown and implant platform had to be filled with prosthetic materials.

Tenocytes of chronic rotator cuff tendon tears can be stimulated by platelet-released growth factors

BACKGROUND Bone-to-tendon healing after rotator cuff repairs is mainly impaired by poor tissue quality. The tenocytes of chronic rotator cuff tendon tears are not able to synthesize normal fibrocartilaginous extracellular matrix (ECM). We hypothesized that in the presence of platelet-released growth factors (PRGF), tenocytes from chronically retracted rotator cuff tendons proliferate and synthesize the appropriate ECM proteins. MATERIALS AND METHODS Tenocytes from 8 patients with chronic rotator cuff tears were cultured for 4 weeks in 2 different media: standard medium (Iscove's Modified Dulbecco's Media + 10% fetal calf serum + 1% nonessential amino acids + 0.5 μg/mL ascorbic acid) and media with an additional 10% PRGF. Cell proliferation was assessed at 7, 14, 21, and 28 days. Messenger (m)RNA levels of collagens I, II, and X, decorin, biglycan, and aggrecan were analyzed using real time reverse-transcription polymerase chain reaction. Immunocytochemistry was also performed. RESULTS The proliferation rate of tenocytes was significantly higher at all time points when cultured with PRGF. At 21 days, the mRNA levels for collagens I, II, and X, decorin, aggrecan, and biglycan were significantly higher in the PRGF group. The mRNA data were confirmed at protein level by immunocytochemistry. CONCLUSIONS PRGFs enhance tenocyte proliferation in vitro and promote synthesis of ECM to levels similar to those found with insertion of the normal human rotator cuffs. CLINICAL RELEVANCE Biologic augmentation of repaired rotator cuffs with PRGF may enhance the properties of the repair tissue. However, further studies are needed to determine if application of PRGF remains safe and effective in long-term clinical studies. LEVEL OF EVIDENCE Basic Science Study, Cell Biology.

On new maximal supergravity and its BPS domain-walls

We revise the SU(3)-invariant sector of N  = 8 supergravity with dyonic SO(8) gaugings. By using the embedding tensor formalism, analytic expressions for the scalar potential, superpotential(s) and fermion mass terms are obtained as a function of the electromagnetic phase ω and the scalars in the theory. Equipped with these results, we explore non-supersymmetric AdS critical points at ω ≠ 0 for which perturbative stability could not be analysed before. The ω-dependent superpotential is then used to derive first-order flow equations and obtain new BPS domain-wall solutions at ω ≠ 0. We numerically look at steepest-descent paths motivated by the (conjectured) RG flows.

Short communication: differential immunoglobulin transfer during mastitis challenge by pathogen-specific components

Mastitis induced by Escherichia coli is often characterized by severe clinical signs, indicating a more powerful combat of the immune system against the pathogen compared with Staphylococcus aureus infections, which are often represented by chronic and subclinical diseases. The aim of this study was to test the major pathogenic component lipopolysaccharide (LPS) from E. coli and lipoteichoic acid (LTA) from Staph. aureus for their effects on blood-milk barrier integrity and the related transfer of immunoglobulins and lactate from blood into milk. A similar somatic cell count (SCC) increase was achieved by intramammary challenge of 1 quarter of 5 cows with 20 µg of LTA, and 8 cows with 0.2 µg of LPS (maximum log SCC/mL: 7). Milk IgG(1) concentrations increased in LPS- but not in LTA-challenged quarters. Milk IgG(2) concentrations were increased in treated quarters at 3h after LPS, and 6h after LTA challenge. Higher maximum levels of IgG(2) were reached in milk of LPS-treated quarters (173 ± 58 μg/mL) than of LTA-challenged quarters (62 ± 13 μg/mL). Immunoglobulin G(1) and IgG(2) levels did not change in control quarters. l-Lactate concentrations in milk increased 4h after LPS and 5h after LTA challenge and reached higher maximum levels in LPS- (221 ± 48 mg/L) than in LTA-treated quarters (77 ± 18 mg/L). In conclusion, a mammary inflammation on a quantitatively similar level based on SCC increase achieves a more efficient transfer of blood components such as IgG(2) via the blood-milk barrier if induced by LPS from E. coli than by LTA from Staph. aureus. This pathogen-specific difference may play an important role in the cure rate of the respective intramammary infection, which is usually lower in Staph. aureus- than in E. coli-induced mastitis.

Mo isotopic composition of the mid-Neoproterozoic ocean: an iron formation perspective

The Neoproterozoic was a major turning point in Earth's surficial history, recording several widespread glaciations, the first appearance of complex metazoan life, and a major increase in atmospheric oxygen. Marine redox proxies have resulted in many different estimates of both the timing and magnitude of the increase in free oxygen, although the consensus has been that it occurred following the Marinoan glaciation, the second globally recorded “snowball Earth” event. A critically understudied rock type of the Neoproterozoic is iron formation associated with the Sturtian (first) glaciation. Samples from the <716 Ma Rapitan iron formation were analysed for their Re concentrations and Mo isotopic composition to refine the redox history of its depositional basin. Rhenium concentrations and Re/Mo ratios are consistently low throughout the bottom and middle of the iron formation, reflecting ferruginous to oxic basinal conditions, but samples from the uppermost jasper layers of the iron formation show significantly higher Re concentrations and Re/Mo ratios, indicating that iron formation deposition was terminated by a shift towards a sulfidic water column. Similarly, the δ98Mo values are close to 0.0‰ throughout most of the iron formation, but rise to ~+0.7‰ near the top of the section. The δ98Mo from samples of ferruginous to oxic basinal conditions are the product of adsorption to hematite, indicating that the Neoproterozoic open ocean may have had a δ98Mo of ~1.8‰. Together with the now well-established lack of a positive Eu anomaly in Neoproterozoic iron formations, these results suggest that the ocean was predominantly oxygenated at 700 Ma.

Combined inhibition of complement C5 and CD14 markedly attenuates inflammation, thrombogenicity, and hemodynamic changes in porcine sepsis

Complement and the TLR family constitute two important branches of innate immunity. We previously showed attenuating effects on inflammation and thromogenicity by inhibiting the TLR coreceptor CD14 in porcine sepsis. In the present study, we explored the effect of the C5 and leukotriene B4 inhibitor Ornithodoros moubata complement inhibitor (OmCI; also known as coversin) alone and combined with anti-CD14 on the early inflammatory, hemostatic, and hemodynamic responses in porcine Escherichia coli-induced sepsis. Pigs were randomly allocated to negative controls (n = 6), positive controls (n = 8), intervention with OmCI (n = 8), or with OmCI and anti-CD14 (n = 8). OmCI ablated C5 activation and formation of the terminal complement complex and significantly decreased leukotriene B4 levels in septic pigs. Granulocyte tissue factor expression, formation of thrombin-antithrombin complexes (p < 0.001), and formation of TNF-α and IL-6 (p < 0.05) were efficiently inhibited by OmCI alone and abolished or strongly attenuated by the combination of OmCI and anti-CD14 (p < 0.001 for all). Additionally, the combined therapy attenuated the formation of plasminogen activator inhibitor-1 (p < 0.05), IL-1β, and IL-8, increased the formation of IL-10, and abolished the expression of wCD11R3 (CD11b) and the fall in neutrophil cell count (p < 0.001 for all). Finally, OmCI combined with anti-CD14 delayed increases in heart rate by 60 min (p < 0.05) and mean pulmonary artery pressure by 30 min (p < 0.01). Ex vivo studies confirmed the additional effect of combining anti-CD14 with OmCI. In conclusion, upstream inhibition of the key innate immunity molecules, C5 and CD14, is a potential broad-acting treatment regimen in sepsis as it efficiently attenuated inflammation and thrombogenicity and delayed hemodynamic changes.