Heart-lung interactions during neurally adjusted ventilatory assist

Introduction Assist in unison to the patient’s inspiratory neural effort and feedback-controlled limitation of lung distension with neurally adjusted ventilatory assist (NAVA) may reduce the negative effects of mechanical ventilation on right ventricular function. Methods Heart–lung interaction was evaluated in 10 intubated patients with impaired cardiac function using esophageal balloons, pulmonary artery catheters and echocardiography. Adequate NAVA level identified by a titration procedure to breathing pattern (NAVAal), 50% NAVAal, and 200% NAVAal and adequate pressure support (PSVal, defined clinically), 50% PSVal, and 150% PSVal were implemented at constant positive end-expiratory pressure for 20 minutes each. Results NAVAal was 3.1 ± 1.1cmH2O/μV and PSVal was 17 ± 2 cmH20. For all NAVA levels negative esophageal pressure deflections were observed during inspiration whereas this pattern was reversed during PSVal and PSVhigh. As compared to expiration, inspiratory right ventricular outflow tract velocity time integral (surrogating stroke volume) was 103 ± 4%, 109 ± 5%, and 100 ± 4% for NAVAlow, NAVAal, and NAVAhigh and 101 ± 3%, 89 ± 6%, and 83 ± 9% for PSVlow, PSVal, and PSVhigh, respectively (p < 0.001 level-mode interaction, ANOVA). Right ventricular systolic isovolumetric pressure increased from 11.0 ± 4.6 mmHg at PSVlow to 14.0 ± 4.6 mmHg at PSVhigh but remained unchanged (11.5 ± 4.7 mmHg (NAVAlow) and 10.8 ± 4.2 mmHg (NAVAhigh), level-mode interaction p = 0.005). Both indicate progressive right ventricular outflow impedance with increasing pressure support ventilation (PSV), but no change with increasing NAVA level. Conclusions Right ventricular performance is less impaired during NAVA compared to PSV as used in this study. Proposed mechanisms are preservation of cyclic intrathoracic pressure changes characteristic of spontaneous breathing and limitation of right-ventricular outflow impedance during inspiration, regardless of the NAVA level.

A clinical prediction model to identify patients at high risk of death in the emergency department.

PURPOSE Rapid assessment and intervention is important for the prognosis of acutely ill patients admitted to the emergency department (ED). The aim of this study was to prospectively develop and validate a model predicting the risk of in-hospital death based on all available information available at the time of ED admission and to compare its discriminative performance with a non-systematic risk estimate by the triaging first health-care provider. METHODS Prospective cohort analysis based on a multivariable logistic regression for the probability of death. RESULTS A total of 8,607 consecutive admissions of 7,680 patients admitted to the ED of a tertiary care hospital were analysed. Most frequent APACHE II diagnostic categories at the time of admission were neurological (2,052, 24 %), trauma (1,522, 18 %), infection categories [1,328, 15 %; including sepsis (357, 4.1 %), severe sepsis (249, 2.9 %), septic shock (27, 0.3 %)], cardiovascular (1,022, 12 %), gastrointestinal (848, 10 %) and respiratory (449, 5 %). The predictors of the final model were age, prolonged capillary refill time, blood pressure, mechanical ventilation, oxygen saturation index, Glasgow coma score and APACHE II diagnostic category. The model showed good discriminative ability, with an area under the receiver operating characteristic curve of 0.92 and good internal validity. The model performed significantly better than non-systematic triaging of the patient. CONCLUSIONS The use of the prediction model can facilitate the identification of ED patients with higher mortality risk. The model performs better than a non-systematic assessment and may facilitate more rapid identification and commencement of treatment of patients at risk of an unfavourable outcome.

Measuring the mechanical properties of plant cells by combining micro-indentation with osmotic treatments

Growth in plants results from the interaction between genetic and signalling networks and the mechanical properties of cells and tissues. There has been a recent resurgence in research directed at understanding the mechanical aspects of growth, and their feedback on genetic regulation. This has been driven in part by the development of new micro-indentation techniques to measure the mechanical properties of plant cells in vivo. However, the interpretation of indentation experiments remains a challenge, since the force measures results from a combination of turgor pressure, cell wall stiffness, and cell and indenter geometry. In order to interpret the measurements, an accurate mechanical model of the experiment is required. Here, we used a plant cell system with a simple geometry, Nicotiana tabacum Bright Yellow-2 (BY-2) cells, to examine the sensitivity of micro-indentation to a variety of mechanical and experimental parameters. Using a finite-element mechanical model, we found that, for indentations of a few microns on turgid cells, the measurements were mostly sensitive to turgor pressure and the radius of the cell, and not to the exact indenter shape or elastic properties of the cell wall. By complementing indentation experiments with osmotic experiments to measure the elastic strain in turgid cells, we could fit the model to both turgor pressure and cell wall elasticity. This allowed us to interpret apparent stiffness values in terms of meaningful physical parameters that are relevant for morphogenesis.

Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV infection.

BACKGROUND Pneumocystis jiroveci pneumonia (PCP) remains the most common opportunistic infection in patients infected with the human immunodeficiency virus (HIV). Among patients with HIV infection and PCP the mortality rate is 10% to 20% during the initial infection and this increases substantially with the need for mechanical ventilation. It has been suggested that corticosteroids adjunctive to standard treatment for PCP could prevent the need for mechanical ventilation and decrease mortality in these patients. OBJECTIVES To assess the effects of adjunctive corticosteroids on overall mortality and the need for mechanical ventilation in HIV-infected patients with PCP and substantial hypoxaemia (arterial oxygen partial pressure < 70 mmHg or alveolar-arterial gradient > 35 mmHg on room air). SEARCH METHODS For the original review we searched The Cochrane Library (2004, Issue 4), MEDLINE (January 1980 to December 2004) and EMBASE (January 1985 to December 2004) without language restrictions. We further reviewed the reference lists from previously published overviews, searched UptoDate version 2005 and Clinical Evidence Concise (Issue 12, 2004), contacted experts in the field and searched the reference lists of identified publications for citations of additional relevant articles.In this update of our review, we searched the above-mentioned databases in September 2010 and April 2014 for trials published since our original review. We also searched for ongoing trials in ClinicalTrials.gov and the World Health Organization International Clinical Trial Registry Platform (ICTRP). We searched for conference abstracts via AEGIS. SELECTION CRITERIA Randomised controlled trials that compared corticosteroids to placebo or usual care in HIV-infected patients with PCP in addition to baseline treatment with trimethoprim-sulfamethoxazole, pentamidine or dapsone-trimethoprim, and reported mortality data. We excluded trials in patients with no or mild hypoxaemia (arterial oxygen partial pressure > 70 mmHg or an alveolar-arterial gradient < 35 mmHg on room air) and trials with a follow-up of less than 30 days. DATA COLLECTION AND ANALYSIS Two teams of review authors independently evaluated the methodology and extracted data from each primary study. We pooled treatment effects across studies and calculated a weighted average risk ratio of overall mortality in the treatment and control groups using a random-effects model.In this update of our review, we used the GRADE methodology to assess evidence quality. MAIN RESULTS Of 2029 screened records, we included seven studies in the review and six in the meta-analysis. Risk of bias varied: the randomisation and allocation process was often not clearly described, five of seven studies were double-blind and there was almost no missing data. The quality of the evidence for mortality was high. Risk ratios for overall mortality for adjunctive corticosteroids were 0.56 (95% confidence interval (CI) 0.32 to 0.98) at one month and 0.59 (95% CI 0.41 to 0.85) at three to four months of follow-up. In adults, to prevent one death, numbers needed to treat are nine patients in a setting without highly active antiretroviral therapy (HAART) available, and 23 patients with HAART available. The three largest trials provided moderate quality data on the need for mechanical ventilation, with a risk ratio of 0.38 (95% CI 0.20 to 0.73) in favour of adjunctive corticosteroids. One study was conducted in infants, suggesting a risk ratio for death in hospital of 0.81 (95% CI 0.51 to 1.29; moderate quality evidence). AUTHORS' CONCLUSIONS The number and size of trials investigating adjunctive corticosteroids for HIV-infected patients with PCP is small, but the evidence from this review suggests a beneficial effect for adult patients with substantial hypoxaemia. There is insufficient evidence on the effect of adjunctive corticosteroids on survival in infants.

Measuring localized viscoelasticity of the vitreous body using intraocular microprobes.

Vitrectomy is a standard ophthalmic procedure to remove the vitreous body from the eye. The biomechanics of the vitreous affects its duration (by changing the removal rate) and the mechanical forces transmitted via the vitreous on the surrounding tissues during the procedure. Biomechanical characterization of the vitreous is essential for optimizing the design and control of instruments that operate within the vitreous for improved precision, safety, and efficacy. The measurements are carried out using a magnetic microprobe inserted into the vitreous, a method known as magnetic microrheology. The location of the probe is tracked by a microscope/camera while magnetic forces are exerted wirelessly by applied magnetic fields. In this work, in vitro artificial vitreous, ex vivo human vitreous and ex vivo porcine vitreous were characterized. In addition, in vivo rabbit measurements were performed using a suturelessly injected probe. Measurements indicate that viscoelasticity parameters of the ex vivo human vitreous are an order of magnitude different from those of the ex vivo porcine vitreous. The in vivo intra-operative measurements show typical viscoelastic behavior of the vitreous with a lower compliance than the ex vivo measurements. The results of the magnetic microrheology measurements were validated with those obtained by a standard atomic force microscopy (AFM) method and in vitro artificial vitreous. This method allows minimally-invasive characterization of localized mechanical properties of the vitreous in vitro, ex vivo, and in vivo. A better understanding of the characteristics of the vitreous can lead to improvements in treatments concerning vitreal manipulation such as vitrectomy.

Immunodeficiency and the risk of cervical intra-epithelial neoplasia 2/3 and cervical cancer: A nested case-control study in the Swiss HIV Cohort Study.

HIV-infected women are at increased risk of cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer (ICC), but it has been difficult to disentangle the influences of heavy exposure to HPV infection, inadequate screening, and immunodeficiency. A case-control study including 364 CIN2/3 and 20 ICC cases matched to 1,147 controls was nested in the Swiss HIV Cohort Study (1985-2013). CIN2/3 risk was significantly associated with low CD4+ cell counts, whether measured as nadir (odds ratio (OR) per 100-cell/μL decrease=1.15, 95% CI: 1.08, 1.22), or at CIN2/3 diagnosis (1.10, 95% CI: 1.04, 1.16). An association was evident even for nadir CD4+ 200-349 versus ≥350 cells/μL (OR=1.57, 95% CI: 1.09, 2.25). After adjustment for nadir CD4+, a protective effect of >2-year cART use was seen against CIN2/3 (OR versus never cART use=0.64, 95% CI: 0.42, 0.98). Despite low study power, similar associations were seen for ICC, notably with nadir CD4+ (OR for 50 versus >350 cells/μL= 11.10, 95% CI: 1.24, 100). HPV16-L1 antibodies were significantly associated with CIN2/3, but HPV16-E6 antibodies were nearly exclusively detected in ICC. In conclusion, worsening immunodeficiency, even at only moderately decreased CD4+ cell counts (200-349 CD4+ cells/μL), is a significant risk factor for CIN2/3 and cervical cancer. This article is protected by copyright. All rights reserved.

Ventilation/perfusion SPECT/CT in patients with pulmonary emphysema. Evaluation of software-based analysing

UNLABELLED The purpose of this study was to evaluate the reproducibility of a new software based analysing system for ventilation/perfusion single-photon emission computed tomography/computed tomography (V/P SPECT/CT) in patients with pulmonary emphysema and to compare it to the visual interpretation. PATIENTS, MATERIAL AND METHODS 19 patients (mean age: 68.1 years) with pulmonary emphysema who underwent V/P SPECT/CT were included. Data were analysed by two independent observers in visual interpretation (VI) and by software based analysis system (SBAS). SBAS PMOD version 3.4 (Technologies Ltd, Zurich, Switzerland) was used to assess counts and volume per lung lobe/per lung and to calculate the count density per lung, lobe ratio of counts and ratio of count density. VI was performed using a visual scale to assess the mean counts per lung lobe. Interobserver variability and association for SBAS and VI were analysed using Spearman's rho correlation coefficient. RESULTS Interobserver agreement correlated highly in perfusion (rho: 0.982, 0.957, 0.90, 0.979) and ventilation (rho: 0.972, 0.924, 0.941, 0.936) for count/count density per lobe and ratio of counts/count density in SBAS. Interobserver agreement correlated clearly for perfusion (rho: 0.655) and weakly for ventilation (rho: 0.458) in VI. CONCLUSIONS SBAS provides more reproducible measures than VI for the relative tracer uptake in V/P SPECT/CTs in patients with pulmonary emphysema. However, SBAS has to be improved for routine clinical use.

Panels of cytokines and other secretory proteins as potential biomarkers of ovarian endometriosis.

Endometriosis is a gynecologic disease that is characterized by nonspecific symptoms and invasive diagnostics. To date, there is no adequate noninvasive method for the diagnosis of endometriosis. Although more than 100 potential biomarkers have been investigated in blood and/or peritoneal fluid, none of these has proven useful in clinical practice. The aim to find a suitable panel of biomarkers that would allow noninvasive diagnosis thus remains of interest. We evaluated the concentrations of 16 cytokines and other secretory proteins in serum and peritoneal fluid of 58 women with ovarian endometriosis (cases) and 40 healthy women undergoing sterilization or patients with benign ovarian cysts (controls) using multiplexed double fluorescence-based immunometric assay platform and enzyme-linked immunosorbent assay. Significantly higher concentrations of glycodelin-A were shown in serum, and significantly higher levels of glycodelin-A, IL-6, and IL-8, and lower levels of leptin were measured in the peritoneal fluid of cases versus controls. In serum, the best performance was shown by models that included the ratio of leptin/glycodelin-A and the ratio of ficolin 2/glycodelin-A, whereas in the peritoneal fluid the best models included the ratio of biglycan/leptin, regulated on activation normal T-cell expressed and secreted/IL-6 and ficolin-2/glycodelin-A, and IL-8 per milligram of total protein, all in combination with age. The models using serum and peritoneal fluid distinguished between ovarian endometriosis patients and controls regardless of the menstrual cycle phase with relatively high sensitivity (72.5% to 84.2%), specificity (78.4% to 91.2%), and area under the curve (0.85 to 0.90).

Mycoplasma-induced minimally conscious state

Mycoplasma pneumoniae (M. pneumoniae) frequently causes community-acquired respiratory tract infection and often presents as atypical pneumonia. Following airborne infection and a long incubation period, affected patients mostly suffer from mild or even asymptomatic and self-limiting disease. In particular in school-aged children, M. pneumoniae is associated with a wide range of extrapulmonary manifestations including central nervous system (CNS) disease. In contrast to children, severe CNS manifestations are rarely observed in adults. We report a case of a 37 year-old previously healthy immunocompetent adult with fulminant M. pneumoniae-induced progressive encephalomyelitis who was initially able to walk to the emergency department. A few hours later, she required controlled mechanical ventilation for ascending transverse spinal cord syndrome, including complete lower extremity paraplegia. Severe M. pneumoniae-induced encephalomyelitis was postulated, and antimicrobial, anti-inflammatory and immunosuppressive therapy was applied on the intensive care unit. Despite early and targeted therapy using four different immunosuppressive strategies, clinical success was limited. In our patient, locked-in syndrome developed followed by persistent minimally conscious state. The neurological status was unchanged until day 230 of follow-up. Our case underlines that severe M. pneumoniae- related encephalomyelitis must not only be considered in children, but also in adults. Moreover, it can be fulminant and fatal in adults. Our case enhances the debate for an optimal antimicrobial agent with activity beyond the blood-brain barrier. Furthermore, it may underline the difficulty in clinical decision making regarding early antimicrobial treatment in M. pneumoniae disease, which is commonly self-limited.

Hyperoxia Exacerbates Myocardial Ischemia in the Presence of Acute Coronary Artery Stenosis in Swine.

BACKGROUND Current guidelines limit the use of high oxygen tension after return of spontaneous circulation after cardiac arrest, focusing on neurological outcome and mortality. Little is known about the impact of hyperoxia on the ischemic heart. Oxygen is frequently administered and is generally expected to be beneficial. This study seeks to assess the effects of hyperoxia on myocardia oxygenation in the presence of severe coronary artery stenosis in swine. METHODS AND RESULTS In 22 healthy pigs, we surgically attached a magnetic resonance compatible flow probe to the left anterior descending coronary artery (LAD). In 11 pigs, a hydraulic occluder was inflated distal to the flow probe. After increasing PaO2 to >300 mm Hg, LAD flow decreased in all animals. In 8 stenosed animals with a mean fractional flow reserve of 0.64±0.02, hyperoxia resulted in a significant decrease of myocardial signal intensity in oxygenation-sensitive cardiovascular magnetic resonance images of the midapical segments of the LAD territory. This was not seen in remote myocardium or in the other 8 healthy animals. The decreased signal intensity was accompanied by a decrease in circumferential strain in the same segments. Furthermore, ejection fraction, cardiac output, and oxygen extraction ratio declined in these animals. Changing PaCO2 levels did not have a significant effect on any of the parameters; however, hypercapnia seemed to nonsignificantly attenuate the hyperoxia-induced changes. CONCLUSIONS Ventilation-induced hyperoxia may decrease myocardial oxygenation and lead to ischemia in myocardium subject to severe coronary artery stenosis.