Modifications of lung microbiota structure in traumatic brain injury ventilated patients according to time and enteral feeding formulas: a prospective randomized study.

BACKGROUND: Specialized diets enriched with immune nutrients could be an important supplement in patients (pts) with acute traumatic brain injury (TBI). Omega-3 and arginine may interact with immune response and microbiota. No data are available about the role of the specialized diets in modulating the lung microbiota, and little is known about the influence of lung microbiota structure in development of ventilator-associated pneumonia (VAP) in TBI pts. The aims of this study are to evaluate the impact of specific nutrients on the lung microbiota and the variation of lung microbiota in TBI pts developing VAP. METHODS: A cohort of 31 TBI pts requiring mechanical ventilation in ICU was randomized for treatment with specialized (16pts) or standard nutrition (15pts). Alpha and beta diversity of lung microbiota were analyzed from bronco Alveolar Lavage (BAL) samples collected at admission and 7 days post-ICU admission in both groups. A further analysis was carried out on the same samples retrospectively grouped in VAP or no VAP pts. RESULTS: None developed VAP in the first week. Thereafter, ten out of thirty-one pts developed VAP. The BAL microbiota on VAP group showed significant differences in beta diversity and Staphylococcus and Acinetobacter Genera were high. The specialized nutrition had influence on beta diversity that reached statistical significance only in Bray-Curtis distance. CONCLUSION: Our data suggest that TBI patients who developed VAP during ICU stay have different structures of BAL microbiota either at admission and at 7 days post-ICU admission, while no correlation has been observed between different enteral formulas and microbiota composition in terms of richness and evenness. These findings suggest that targeting the lung microbiota may be a promising approach for preventing infections in critically ill patients.

Accountable care organization reform: past challenges and future opportunities for public health.

OBJECTIVES: This study aimed to analyze the regulatory landscape that governs accountable care organizations (ACOs) in the United States and the effects on organizational participation. STUDY DESIGN: This was a descriptive study of existing and prior regulations that govern ACOs in the United States. In addition, we analyze data on ACO participation over time. METHODS: We used content analysis methods to the regulatory framework governing ACOs. Authors read and analyzed all regulations since 2012. RESULTS: ACO participation has been undermined by a shifting regulatory landscape. Under the Trump administration, ACOs have had to take on additional risk earlier and that has contributed to the lowest number of participating organizations in the program's history. CONCLUSIONS: The Biden administration has the opportunity to remake regulations governing ACO development and support.

Validation of carbon dioxide production (VCO2) as a tool to calculate resting energy expenditure (REE) in mechanically ventilated critically ill patients: a retrospective observational study.

BACKGROUND: Indirect calorimetry (IC) measurement is considered the gold standard for the assessment of resting energy expenditure (REE). It is based on the measurement of oxygen and carbon dioxide consumption (VO2 and VCO2, respectively). However, its use is limited by cost and technical issues. It has been proposed that, in critically ill patients, the analysis of VCO2 obtained from the ventilator alone may be used as an accurate method to assess REE in ventilated patients. This retrospective study aimed to assess the accuracy of VCO2 measurement alone in the determination of REE. METHODS: This was a retrospective study conducted at the general intensive care unit of a single university-affiliated tertiary medical center. Patients included were invasively ventilated and their REE was measured by using IC. The respiratory quotients (RQs) were set at 0.8, 0.85, and 0.89. Data were collected from computerized patient files. REE obtained from the ventilator by using VCO2 (REE-VCO2) alone was compared with REE obtained from IC (REE-IC). RESULTS: Measurements were obtained for 80 patients, and 497 REE-IC measurements were compared with REE-VCO2 obtained at the same time. The mean REE-IC was 2059.5 ± 491.7 kcal/d. The mean REE-RQs corresponding to RQs of 0.80, 0.85, and 0.89 were 1936.8 ± 680.0, 2017.8 ± 708.8, and 2122.1 ± 745.4 kcal/d, respectively. REE-VCO2 derived from an RQ of 0.85 had the lowest mean difference from REE-IC. Whereas accuracy was higher using an RQ of 0.85, agreement (between 85% and 115%) was highest using an RQ of 0.89. CONCLUSIONS: The level of agreement of REE obtained from VCO2 readings with REE obtained from IC was generally low. IC continues to be the recommended method for REE assessment.

NMR spin-rotation relaxation and diffusion of methane.

The translational diffusion-coefficient and the spin-rotation contribution to the 1H NMR relaxation rate for methane (CH4) are investigated using MD (molecular dynamics) simulations, over a wide range of densities and temperatures, spanning the liquid, supercritical, and gas phases. The simulated diffusion-coefficients agree well with measurements, without any adjustable parameters in the interpretation of the simulations. A minimization technique is developed to compute the angular velocity for non-rigid spherical molecules, which is used to simulate the autocorrelation function for spin-rotation interactions. With increasing diffusivity, the autocorrelation function shows increasing deviations from the single-exponential decay predicted by the Langevin theory for rigid spheres, and the deviations are quantified using inverse Laplace transforms. The 1H spin-rotation relaxation rate derived from the autocorrelation function using the "kinetic model" agrees well with measurements in the supercritical/gas phase, while the relaxation rate derived using the "diffusion model" agrees well with measurements in the liquid phase. 1H spin-rotation relaxation is shown to dominate over the MD-simulated 1H-1H dipole-dipole relaxation at high diffusivity, while the opposite is found at low diffusivity. At high diffusivity, the simulated spin-rotation correlation time agrees with the kinetic collision time for gases, which is used to derive a new expression for 1H spin-rotation relaxation, without any adjustable parameters.

Role of internal motions and molecular geometry on the NMR relaxation of hydrocarbons.

The role of internal motions and molecular geometry on 1H NMR relaxation rates in liquid-state hydrocarbons is investigated using MD (molecular dynamics) simulations of the autocorrelation functions for intramolecular and intermolecular 1H-1H dipole-dipole interactions. The effects of molecular geometry and internal motions on the functional form of the autocorrelation functions are studied by comparing symmetric molecules such as neopentane and benzene to corresponding straight-chain alkanes n-pentane and n-hexane, respectively. Comparison of rigid versus flexible molecules shows that internal motions cause the intramolecular and intermolecular correlation-times to get significantly shorter, and the corresponding relaxation rates to get significantly smaller, especially for longer-chain n-alkanes. Site-by-site simulations of 1H's across the chains indicate significant variations in correlation times and relaxation rates across the molecule, and comparison with measurements reveals insights into cross-relaxation effects. Furthermore, the simulations reveal new insights into the relative strength of intramolecular versus intermolecular relaxation as a function of internal motions, as a function of molecular geometry, and on a site-by-site basis across the chain.

Time-resolved IR spectroscopy of a trinuclear palladium complex in solution.

This paper presents a combined spectroscopic and theoretical analysis of a trinuclear [Pd3{Si(mt(Me))3}2] complex (mt(Me) = methimazole) which has been demonstrated to be a potential catalyst for coupling reactions. It is a highly symmetric model system (D3 in the electronic ground state) for the investigation of electronic states and the structure of polynuclear transition metal complexes. Different time-resolved IR spectroscopic methods covering the femtosecond up to the microsecond range as well as density functional computations are performed to unravel the structure and character of this complex in the electronically excited state. These are the first time-resolved IR studies on a trinuclear Pd complex. Based on the interplay between the computational results and those from the IR studies a (3)A state is identified as the lowest lying triplet state which has C2 symmetry.

Brain death determination in Israel: the first two years experience following changes to the brain death law-opportunities and challenges.

To increase support for the concept of brain death, changes accommodating requirements of the religious authorities were made to the Brain Death Act in Israel. These included (1) considering patient wishes regarding brain death determination (BDD); (2) mandatory performance of apnea and ancillary testing; (3) establishment of an accreditation committee and (4) requirement for physician training courses. We describe the first 2 years experience following implementation (2010-2011). During 2010, the number of BDD decreased from 21.9/million population (during the years 2007-2009) to 16.0 (p < 0.001). Reasons included family resistance to brain death testing (27 cases), inability to perform apnea testing (7) and logistic problems related to ancillary testing (26 cases). The number of physicians available to declare brain death also decreased (210 vs. 102). During 2011, BDDs increased to 20.5/million following the introduction of radionuclide angiography as an ancillary test; other reasons for nondetermination persisted (family resistance 26 cases, inability to perform apnea testing 10 cases). Instead of increasing opportunities, many obstacles were encountered following the changes to the Brain Death Act. Although some of these challenges have been met, longer term follow-up is required to assess their complete impact.

Off-hour effects on stroke care and outcome in stroke centres.

BACKGROUND AND PURPOSE: Poorer stroke care processes and outcomes have been reported for acute stroke patients arriving at centres during off hours and weekends. OBJECTIVE: To compare each step of the continuous specialized care that Stroke Centres (SC) provide according to time of admission and final outcome. METHODS: Observational study of consecutive stroke patients admitted to SC during 2008 and 2009. Patients were classified into two groups according to their arrival time: Work Hours (WH) and Off Hour (OH) (weekends and any time other than 8:00 am to 3:00 pm on weekdays). Differences in time to diagnostic procedures, tPA administration, stroke outcome [modified Rankin Scale, (mRS)] and in-hospital fatality rates were analysed. RESULTS: A total of 912 patients were admitted. Data from 674 patients fulfilling study criteria were analysed. A total of 434 (64.4%) patients arrived during OH. No differences in stroke severity were found when comparing OH and WH. Time to blood test results was higher for WH (median 67 min vs. 47 min; P < 0.01), but time to cranial CT scan was similar. Intravenous tPA was administered to 58 (16.4%) OH vs. 26 (13.1%) WH patients (P = 0.33). OH arrival was not associated with poorer outcome (mRS ≥ 3) at discharge (32.8% vs. 37%; P = 0.27), or at the 3-month follow-up (30.6% vs. 27.6%, P = 0.52). No differences were found for in-hospital fatality rates (5.8% vs. 5.4%, P = 1.00). CONCLUSIONS: The care provided by SC with neurologists on call 24/7 prevents differences in outcomes associated with time of admission and guarantees equal attention to stroke patients.

Organ transplantation from a donor colonized with a multidrug-resistant organism: a case report.

The number of intensive care unit patients with infections caused by multidrug-resistant organisms is increasing in most developed countries. We report the case of a deceased multiorgan donor, who was an asymptomatic carrier of carbapenem-resistant Klebsiella pneumoniae (CR-KP) in the respiratory tract, a condition that was not diagnosed before organ harvesting and transplantation. The outcome of the 2 kidney recipients, the liver recipient, and 1 of the lung recipients was uneventful; in particular, no evidence of infection transmission or adverse graft outcomes was noted. The other lung recipient had a complicated postoperative course and, 4 weeks post transplantation, he developed a bacteremic pneumonia with CR-KP from which he subsequently died. These results suggest that, in well defined conditions, organs from donors who are CR-KP positive may be considered for transplantation.

[Omega-3 fatty acids as an option in the treatment of NAFLD]. / Omega-3-Fettsäuren alsTherapieoption für NAFLD.

BACKGROUND: Human tissues or organs vary in the content of long-chain omega-3 fatty acids, in case of diseases the content may even change. These findings cannot be extrapolated from blood lipids. METHODS: Overview RESULTS: By means of liver biopsies it has been shown that eicosapentaenoic acid (EPA) significantly decreases with raising triglyceride accumulation in hepatocytes. This is associated with increased histological signs of inflammation in liver parenchyma. In a study the intake of omega-3 fatty acids (1 g/d) resulted in a rising percentage of EPA in liver triglycerides associated with a reduction of liver fat and inflammation markers. CONCLUSION: From the results a hitherto widely ignored indication for NAFLD with or without metabolic syndrome can be derived.

TICACOS international: A multi-center, randomized, prospective controlled study comparing tight calorie control versus Liberal calorie administration study.

Since the first TICACOS study, 3 additional studies have been published comparing a medical nutrition therapy guided by indirect calorimetry to a regimen prescribed on the basis of predictive equations. A recent guidelines document included a meta-analysis including these 4 papers and found a trend for improvement (OR 0.98-1.48) in favor of medical nutrition therapy guided by indirect calorimetry in terms of survival. The aim of our study was to perform a multicenter prospective, randomized, controlled non blinded study in critically patients to assess the added value for measuring daily resting energy expenditure as a guide for nutritional support. The primary objective was to decrease infectious rate of these critically ill patients. MATERIAL AND METHODS: This phase III, multi-center, randomized, controlled non blinded study was planned to include 580 newly-admitted, adult ventilated ICU patients that were planned to stay more than 48 h in the ICU departments. The nutritional support was aimed to meet 80-100% of energy requirement measured by indirect calorimetry. The calorie needs were determined by IC in the Study group and by an equation (20-25 kcal/kg ideal body weight/day) in the Control Group. The ICU staff was trained to strive to supply 80-100% of a patient's energy requirements through artificial nutrition, preferably enteral feeding. Primary endpoint was infection rate and secondary endpoints included other morbidities and mortality during ICU, at 90 and 180 days. Comparison between the study and the control group was performed using T test for equality of means (independent samples test). Correlations were performed using the Pearson correlation test. A p level of 0.05 or below was considered as significant. Cross tabs procedure used Chi-square test for testing differences in complication rates, length of stay and length of ventilation. Correlations between energy balances and complications was also be tested using one way analysis as well as ANOVA analysis between groups and within groups. Kaplan Meir curves assessed the proportion of surviving patients in the 2 groups. RESULTS: Seven centers with a calorimeter available participated to the study. Due to slow inclusion rate, the study was stopped after 6 years and after inclusion of 417 patients only. From the 417 intended to treat patients, 339 followed the protocol. There was no differences between control and study groups in terms of age, sex BMI, SOFA (7.1 ± 3.1 vs 7.4 ± 3.3) and APACHE II scores (22.4 ± 7.9 vs 22.2 ± 7.4). The rate of infection (40 vs 31), including pneumonia rate, need for surgery, dialysis requirement, length of ventilation, ICU length of stay, and hospital length of stay were not different between groups. Mortality (30 in the control vs 21 in the study group) was not significantly different between groups. The decreased mortality observed in the study group when added to previous studies may have a positive effect on the meta-analysis previously published. CONCLUSION: Tight Calorie Control guided by indirect calorimetry decreased the rate of infection and mortality but not significantly. This may be explained by the not relatively small sample size. There results together with the previous 4 prospective randomized studies, may improve the results of the meta-analysis exploring the effects of IC guided nutrition on mortality.

Reducing the knowledge to action gap in hospital nutrition care - Developing and implementing nutritionDay 2.0.

BACKGROUND & AIMS: In hospital nutrition care the difficulty of translating knowledge to action often leads to inadequate management of patients with malnutrition. nutritionDay, an annual cross-sectional survey has been assessing nutrition care in healthcare institutions in 66 countries since 2006. While initial efforts led to increased awareness of malnutrition, specific local remedial actions rarely followed. Thus, reducing the Knowledge-to-action (KTA) gap in nutrition care requires more robust and focused strategies. This study describes the strategy, methods, instruments and experience of developing and implementing nutritionDay 2.0, an audit and feedback intervention that uses quality and economic indicators, feedback, benchmarking and self-defined action strategies to reduce the KTA gap in hospital nutrition care. METHODS: We used an evidence based multi-professional mixed-methods approach to develop and implement nutritionDay 2.0 This audit and feedback intervention is driven by a Knowledge-to-Action framework complemented with robust stakeholder analysis. Further evidence was synthesized from the literature, online surveys, a pilot study, World Cafés and individual expert feedback involving international health care professionals, nutrition care scientists and patients. RESULTS: The process of developing and implementing nutritionDay 2.0 over three years resulted in a new audit questionnaire based on 36 nutrition care quality and economic indicators at hospital, unit and patient levels, a new action-oriented feedback and benchmarking report and a unit-level personalizable action plan template. The evaluation of nutritionDay 2.0 is ongoing and will include satisfaction and utility of nutritionDay 2.0 tools and short-, mid- and long-term effects on the KTA gap. CONCLUSION: In clinical practice, nutritionDay 2.0 has the potential to promote behavioural and practice changes and improve hospital nutrition care outcomes. In research, the data generated advances knowledge about institutional malnutrition and quality of hospital nutrition care. The ongoing evaluation of the initiative will reveal how far the KTA gap in hospital nutrition care was addressed and facilitate the understanding of the mechanisms needed for successful audit and feedback. TRIAL REGISTRATION: Registration in clinicaltrials.gov: Identifier: NCT02820246.

Tolerance-related V beta clonal deletions in normal CD4-8-, TCR-alpha/beta + and abnormal lpr and gld cell populations.

We have analyzed tolerance-related clonal deletion of Mls-and I-E-reactive thymocytes at the RNA level using a multi-V beta probe RNAse protection assay, and used this phenomenon to identify the maturation stage of the abnormally expanded CD4-8-, TCR-alpha/beta + subset in lpr and gld homozygous mice, and of the phenotypically similar minor thymocyte subset found in normal mice. Essentially complete V beta clonal deletions were detected in lpr and gld cells of all appropriate background strains. Substantial, but not complete, V beta clonal deletions were also detected in the CD4-8- TCR-alpha/beta + subset of normal mice. Since expression of CD4/CD8 is required for V beta clonal deletions to occur, we conclude that lpr and gld cells, and at least a portion of CD4-8- TCR-alpha/beta + thymocytes in normal mice, are derived by secondary loss of CD4/CD8 accessory molecules from more mature CD4+8+ precursors. One possible interpretation of these findings is that such CD4/CD8 loss may affect a class of self-reactive thymocytes that have escaped direct clonal deletion. Exportation and expansion of such cells in the periphery may be an important contributory factor in the induction of systemic autoimmunity.

Delineation of a defect in T cell receptor beta genes of NZW mice predisposed to autoimmunity.

In an attempt to determine whether genes involved in T cell antigen recognition are structurally abnormal and thereby promote murine systemic lupus, we analyzed the structural integrity of the D, J, and C region elements of the T cell receptor alpha and beta chain genes in all major lupus strains and several normal strains. Within the limits of restriction fragment length polymorphism analysis, all strains had an identical genomic organization, except the NZW mice, in which a deletion of the C beta 1-D beta 2-J beta 2 elements was found. Sequence analysis of NZW genomic elements containing this deletion placed its probable origin within the first exon of C beta 1, and extending to a complementary region within the first exon of C beta 2. The significance of this abnormality in the pathogenesis of systemic autoimmune disease remains to be determined.

Acidic mine drainage: the rate-determining step.

The rate-determining step in the oxidation of iron pyrite and the formation of acidity in streams associated with coal and copper mines is the oxidation of ferrous iron. Effective pollution abatement necessitates control ling this reaction.

Harnessing genomics and biotechnology to improve global health equity.

With decisive and timely action, genome-related biotechnology can be harnessed to improve global health equity. In June 2002 in Kananaskis, Canada, leaders of the G8 industrial nations will develop an action plan to support implementation of the New African Initiative. By extending their discussion of health issues raised in the New African Initiative to include genomics, G8 leaders could signal their intention to increase global health equity by preventing a health genomics divide from developing. There are already some early and growing examples of genome-related biotechnology being applied successfully to health problems in developing countries. But how can genomics be systematically harnessed to benefit health in developing countries? We propose a five-point strategy, including research, capacity strengthening, consensus building, public engagement, and an investment fund.

The hydrolytic water molecule in trypsin, revealed by time-resolved Laue crystallography.

Crystals of bovine trypsin were acylated at the reactive residue, serine 195, to form the transiently stable p-guanidinobenzoate. Hydrolysis of this species was triggered in the crystals by a jump in pH. The hydrolysis was monitored by three-dimensional Laue crystallography, resulting in three x-ray diffraction structures, all from the same crystal and each representing approximately 5 seconds of x-ray exposure. The structures were analyzed at a nominal resolution of 1.8 angstroms and were of sufficient quality to reproduce subtle features in the electron-density maps for each of the structures. Comparison of the structures before and after the pH jump reveals that a water molecule has positioned itself to attack the acyl group in the initial step of the hydrolysis of this transient intermediate.

Mutagenesis and Laue structures of enzyme intermediates: isocitrate dehydrogenase.

Site-directed mutagenesis and Laue diffraction data to 2.5 A resolution were used to solve the structures of two sequential intermediates formed during the catalytic actions of isocitrate dehydrogenase. Both intermediates are distinct from the enzyme-substrate and enzyme-product complexes. Mutation of key catalytic residues changed the rate determining steps so that protein and substrate intermediates within the overall reaction pathway could be visualized.

Prognostic value of energy expenditure and respiratory quotient measuring in patients with liver cirrhosis.

BACKGROUND & AIMS: Resting energy expenditure (REE) and respiratory quotient (RQ) as measured by indirect calorimetry (IC) may correlate with muscle mass and represent prognostic indicators in treating patients with liver cirrhosis. We aimed to assess the correlation of IC-measured REE and RQ with skeletal muscle mass (SM), mortality, and REE values as estimated by Harris-Benedict, European guidelines (EG), and Brazilian guidelines-DITEN (BG) equations in patients with liver cirrhosis. METHODS: In this prospectively designed study, REE was measured in 126 male patients with liver cirrhosis by IC and predicted by Harris-Benedict, EG (35 kcal/kg current weight), and BG (30 kcal/kg current weight) guidelines. Measurements were obtained at the time of admission to the study. Body composition was determined by whole-body dual-energy X-ray absorptiometry. The association between REE and 3-year survival was investigated. RESULTS: Cirrhosis etiology was classified as alcohol related (59.0%), viral (20.1%), cryptogenic (11.8%), or other (9.0%). Mean Child-Pugh and MELD indexes were 8.30 ± 2.0 and 14.38 ± 6.12, respectively. RQ showed a moderate correlation with SM (r = 0.64), while IC-measured REE was inversely associated with mortality (multivariate Cox Regression, HR = 0.88, 95% CI: 0.78; 1, p = 0.04). Among the predictive equations for REE, only Harris-Benedict yielded values close to the IC, with a positive Pearson correlation (r = 0.77), excellent accuracy (Cb = 0.98), and positive Lin's concordance correlation (CCC = 0.75). However, a large standard deviation was observed; HB-measured REE did not correlate with mortality. CONCLUSIONS: RQ and REE, as measured by IC, may be valuable tools for evaluating the severity of cirrhosis, by reflecting SM and predicting mortality, respectively. The predictive equations for REE included in this study cannot replace IC for this purpose. REGISTERED AT: www.clinicalTrials.gov (NCT02421848).