Development and Validation of Scores to Predict Prolonged Mechanical Ventilation after Cardiac Surgery.

OBJECTIVES: To optimize the early prediction of prolonged postoperative mechanical ventilation after cardiac surgery (>24 hours postoperatively). DESIGN: The authors performed a retrospective analysis. SETTING: The Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) database was utilized. PARTICIPANTS: All patients included in the ANZSCTS database between January 2015 and December 2018 were analyzed. INTERVENTIONS: No interventions were performed in this observational study. MEASUREMENTS AND MAIN RESULTS: A previously developed model was modified to allow retrospective risk calculation and model assessment (Modified Hessels score). The database was split into development and validation sets. A new risk model was developed using forward and backward stepwise elimination (ANZ-PreVent score). The authors assessed 48,382 patients, of whom 5004 (10.3%) were ventilated mechanically for >24 hours post-operatively. The Modified Hessels score demonstrated good performance in this database, with a c-index of 0.78 (95% CI 0.77-0.78) and a Brier score of 0.08. The newly developed ANZ-PreVent score demonstrated better performance (validation cohort, n = 12,229), with a c-index of 0.84 (95% CI 0.83-0.85) (p < 0.0001) and a Brier score of 0.07. Both scores performed better than the severity of illness scores commonly used to predict outcomes in intensive care. CONCLUSIONS: The authors validated a modified version of an existing prediction score and developed the ANZ-PreVent score, with improved performance for identifying patients at risk of ventilation for >24 hours. The improved score can be used to identify high-risk patients for targeted interventions in future randomized controlled trials.

Complete genome sequences of cluster F1 and cluster B1 Mycobacterium smegmatis phages Karhdo and Basato.

We present the complete genome sequences of Mycobacterium smegmatis phages Karhdo and Basato, isolated in Clark County, Nevada. The phages were isolated and annotated by students enrolled in undergraduate research courses over two semesters at the University of Nevada, Las Vegas.

Hyperoncotic Albumin Solution in Continuous Renal Replacement Therapy Patients.

AIM: The aim of this study was to investigate the association of hyperoncotic (20%) human albumin solution (HAS) with outcomes among critically ill patients receiving continuous renal replacement therapy (RRT). METHODS: Analysis of the Randomized Evaluation of Normal versus Augmented Level (RENAL) RRT trial data. RESULTS: Of 1,508 patients, 771 (51%) received albumin. Of these, 345 (45%) received 4% HAS only, 155 (20%) received 20% HAS only, and 271 (35%) received both. Patients who received combined 4% and 20% HAS were more severely ill, received more days of RENAL trial therapy and required mechanical ventilation for longer. Mean daily fluid balance was -288 mL (-904 to 261) with 20% HAS only versus 245 mL (-248 to 1,050) with 4% HAS only (p < 0.001). On Cox proportional hazards regression, 20% HAS exposure was not associated with greater 90-day mortality (odds ratio 1.12, 95% confidence interval [CI]: 0.77-1.62; p = 0.55) or longer recovery to RRT independence (sub-hazard ratio 1.04, 95% CI: 0.84-1.30; p = 0.70) compared to those who received 4% HAS only. CONCLUSIONS: RENAL trial patients commonly received albumin in varying concentrations. The administration of 20% HAS was associated with a more negative fluid balance but was not independently associated with increased mortality or RRT dependence when compared to 4% HAS only.

Varying association of laboratory values with reference ranges and outcomes in critically ill patients: an analysis of data from five databases in four countries across Asia, Europe and North America.

BACKGROUND: Despite wide usage across all areas of medicine, it is uncertain how useful standard reference ranges of laboratory values are for critically ill patients. OBJECTIVES: The aim of this study is to assess the distributions of standard laboratory measurements in more than 330 selected intensive care units (ICUs) across the USA, Amsterdam, Beijing and Tarragona; compare differences and similarities across different geographical locations and evaluate how they may be associated with differences in length of stay (LOS) and mortality in the ICU. METHODS: A multi-centre, retrospective, cross-sectional study of data from five databases for adult patients first admitted to an ICU between 2001 and 2019 was conducted. The included databases contained patient-level data regarding demographics, interventions, clinical outcomes and laboratory results. Kernel density estimation functions were applied to the distributions of laboratory tests, and the overlapping coefficient and Cohen standardised mean difference were used to quantify differences in these distributions. RESULTS: The 259 382 patients studied across five databases in four countries showed a high degree of heterogeneity with regard to demographics, case mix, interventions and outcomes. A high level of divergence in the studied laboratory results (creatinine, haemoglobin, lactate, sodium) from the locally used reference ranges was observed, even when stratified by outcome. CONCLUSION: Standardised reference ranges have limited relevance to ICU patients across a range of geographies. The development of context-specific reference ranges, especially as it relates to clinical outcomes like LOS and mortality, may be more useful to clinicians.

Early Treatment with Human Albumin Solution in Continuous Renal Replacement Patients.

AIMS: To study the impact of early human albumin solution (HAS) in continuous renal replacement therapy (RRT) patients. METHODS: Analysis of Randomized Evaluation of Normal versus Augmented Level (RENAL) RRT trial data. RESULTS: Of 1,464 patients, 500 (34%) received early albumin. These patients had higher illness severity scores, greater use of mechanical ventilation, and 90-day mortality (51 vs. 41%; p < 0.001). However, early albumin carried similar RRT dependence risk among survivors at day 90 (4.9 vs. 5.8%; p = 0.62). On Cox proportional hazards regression, with standardized inverse probability of treatment weighting, early albumin was not associated with increased mortality (hazard ratio [HR]: 1.23, 95% CI: 0.97-1.55; p = 0.09) or recovery to RRT independence (HR: 0.92, 95% CI: 0.78-1.10; p = 0.38). CONCLUSIONS: Early albumin was administered to one-third of RENAL trial patients and in those with greater illness severity. Early albumin was not independently associated with mortality risk or rate of recovery to RRT independence.

Haemodynamic effect of a 20% albumin fluid bolus in post-cardiac surgery patients.

OBJECTIVE: To study the cardiovascular effect over 30 minutes following the end of fluid bolus therapy (FBT) with 20% albumin in patients after cardiac surgery. DESIGN: Prospective observational study. SETTING: Intensive care unit of a tertiary university-affiliated hospital. PARTICIPANTS: Twenty post-cardiac surgery mechanically ventilated patients with a clinical decision to administer FBT. INTERVENTION: FBT with a 100 mL bolus of 20% albumin. MAIN OUTCOME MEASURES: Cardiac index (CI) response was defined by a ≥ 15% increase, while mean arterial pressure (MAP) response was defined by a ≥ 10% increase. RESULTS: The most common indication for FBT was hypotension (40%). Median duration of infusion was 7 minutes (interquartile range [IQR], 3-9 min). At the end of FBT, five patients (25%) showed a CI response, which increased to almost half in the following 30 minutes and dissipated in one patient. MAP response occurred in 11 patients (55%) and dissipated in five patients (45%) by a median of 6 minutes (IQR, 6-10 min). CI and MAP responses coexisted in four patients (20%). An intrabolus MAP response occurred in 17 patients (85%) but dissipated in 11 patients (65%) within a median of 7 minutes (IQR, 2-11 min). On regression analysis, faster fluid bolus administration predicted MAP increase at the end of the bolus. CONCLUSION: In post-cardiac surgery patients, CI response to 20% albumin FBT was not congruous with MAP response over 30 minutes. Although hypotension was the main indication for FBT and a MAP response occurred in most of patients, such response was maximal during the bolus, dissipated in a few minutes, and was dissociated from the CI response.

Sex and mortality in septic severe acute kidney injury.

PURPOSE: To investigate the relationship between sex and mortality and whether menopause or the intensity of renal replacement therapy (RRT) modify this relationship in patients with severe septic acute kidney injury (AKI). MATERIALS AND METHODS: Post-hoc analysis of patients with sepsis included in the Randomized Evaluation of Normal versus Augmented Level renal replacement therapy (RENAL) trial. RESULTS: Of 724 patients, 458 (63.3%) were male and 266 (36.7%) were female. The mean delivered effluent flow rate was 25.6 ±â€¯7.4 ml/kg/h (80 ±â€¯15% of prescribed dose) in males and 27.4 ±â€¯7.6 ml/kg/h (83 ±â€¯15% of prescribed dose) in females (p = .01). A total of 237 (51.7%) males and 118 (44.5%) females died within 90 days of randomization (p = .06). The adjusted hazard ratio (HR) for 90-day mortality was significantly decreased in females as compared with males (HR 0.74, 95% CI 0.57 to 0.96, p = .02). The relationship between sex and mortality was not significantly altered by menopausal status (adjusted P value for interaction 0.99) or by RRT intensity allocation (adjusted P value for interaction 0.27). CONCLUSIONS: In a cohort of patients with sepsis and severe AKI, female sex was associated with improved survival. The relationship between sex and survival was not altered by menopausal status or RRT intensity.

Higher versus Lower Continuous Renal Replacement Therapy Intensity in Critically ill Patients with Liver Dysfunction.

AIMS: To study the association between higher versus lower continuous renal replacement therapy (CRRT) intensity and mortality in critically ill patients with combined acute kidney injury and liver dysfunction. METHODS: Post-hoc analysis of patients with liver dysfunction (Sequential Organ Failure Assessment liver score ≥2 or diagnosis of liver failure/transplant) included in the Randomized Evaluation of Normal versus Augmented Level renal replacement therapy (RENAL) trial. RESULTS: Of 444 patients, 210 (47.3%) were randomized to higher intensity (effluent flow 40 mL/kg/h) and 234 (52.7%) to lower intensity (effluent flow 25 mL/kg/h) therapy. Overall, 79 and 86% of prescribed effluent flow was delivered in the higher-intensity and lower-intensity groups, respectively (p < 0.001). In total, 113 (54.1%) and 120 (51.3%) patients died in each group. On multivariable Cox regression analysis, we found no independent association between higher CRRT intensity and mortality (HR 0.93, 95% CI 0.70-1.24; p = 0.642). CONCLUSIONS: In RENAL patients with liver dysfunction, higher CRRT intensity was not associated with reduced mortality.

Crystal Fluidity Reflected by Fast Rotational Motion at the Core, Branches, and Peripheral Aromatic Groups of a Dendrimeric Molecular Rotor.

Low packing densities are key structural features of amphidynamic crystals built with static and mobile components. Here we report a loosely packed crystal of dendrimeric rotor 2 and the fast dynamics of all its aromatic groups, both resulting from the hyperbranched structure of the molecule. Compound 2 was synthesized with a convergent strategy to construct a central phenylene core with stators consisting of two layers of triarylmethyl groups. Single crystal X-ray diffraction analysis confirmed a low-density packing structure consisting of one molecule of 2 and approximately eight solvent molecules per unit cell. Three isotopologues of 2 were synthesized to study the motion of each segment of the molecule in the solid state using variable temperature quadrupolar echo (2)H NMR spectroscopy. Line shape analysis of the spectra reveals that the central phenylene, the six branch phenylenes, and the 18 periphery phenyls all display megahertz rotational dynamics in the crystals at ambient temperature. Arrhenius analysis of the data gives similar activation energies and pre-exponential factors for different parts of the structure. The observed pre-exponential factors are 4-6 orders of magnitude greater than those of elementary site-exchange processes, indicating that the dynamics are not dictated by static energetic potentials. Instead, the activation energies for rotations in the crystals of 2 are controlled by temperature dependent local structural fluctuations and crystal fluidity.

Ferrocenyl chalcones versus organic chalcones: a comparative study of their nematocidal activity.

A series of 30 organic chlacones and 33 ferrocenyl (Fc) chalcones were synthesized and characterized by melting point, elemental analysis, spectroscopy ((1)H NMR and FTIR) and, in two cases, by X-ray crystallography. The biological activity of each compound (10(-4)M in DMSO) against the model nematode Caenorhabditis elegans was examined in terms of % mortality (percent nematodes that died) and % fecundity (percent nematodes that reproduced) and compared to that obtained for the control medium (1% DMSO) over a 14-day period. Detailed conformational analyses for two Fc-chalcones (studied also by X-ray crystallography) were performed via molecular modeling studies. In general, the organic chalcones were found to be less polar than their Fc analogs. Some structure-activity relationships (SARs) were determined: (a) The nematocidal activities of the organic chalcones in this series were found to be much greater than those of their ferrocenyl analogs. (b) The position of the carbonyl group played a central role in the biological activity of both classes of chalcones studied. (c) For both classes of chalcones, lipophilicity of a compound seemed to play a significant role in its nematocidal activity. (d) The planarity of a ferrocenyl-chlacone seems to play a role in its activity.

Solid-state molecular rotors with perdeuterated stators: mechanistic insights from biphenylene rotational dynamics in ordered and disordered crystal forms.

Samples of 4,4'-bis(3,3,3-tri-d(5)-phenylpropynyl)biphenyl 2, 9,10-bis(3,3,3-tri-d(5)-phenylpropynyl)anthracene 3, 1,4-bis(3,3,3-tri-d(5)-phenylpropynyl)naphthalene 4, and 4,4'-bis(3,3,3-tri-d(5)-phenylpropynyl)-1,1'-binaphthyl 5 were prepared via a Sonogashira coupling of 3,3,3-tri-d(5)-phenylpropyne 7 and the appropriate aryl dibromide. Single crystal X-ray diffraction structures were obtained for an o-xylene clathrate of 2 and for solvent-free crystals of 3. All four molecular rotors were characterized by CPMAS (13)C NMR experiments with varying contact times in order to determine whether the carbon signals of the central rotator group could be selectively enhanced and studied without interference or overlap of signals from the deuterated stator, which is insensitive to the {(1)H}-(13)C cross-polarization method. It was shown that the (13)C signals of the natural abundance rotator group can be selectively observed with short contact times (ca. 50 micros) without interference from other (13)C signals in the molecule. Variable-temperature CPMAS (13)C NMR studies with a crystalline o-xylene solvate of biphenylene rotor 2 suggested a 2-fold flipping process in the fast exchange regime, even at temperatures as low as 199 K (-74 degrees C). Indirect support for this was obtained by studies carried out with a disordered, solvent-free solid, obtained by fast precipitation from hexanes and dichloromethane, which displayed slower dynamics within the same temperature range with an activation energy of 8.7 kcal/mol and a pre-exponential factor of 4.9 x 10(9) s(-1). Confirmation of an exchange process in the megahertz regime for the crystalline solvate was obtained by variable-temperature quadrupolar echo (2)H NMR data acquired with samples prepared with a deuterated biphenylene rotator and a natural abundance stator. Although rotational exchange occurs in the solvated samples with a slightly lower barrier of 7.4 kcal/mol, the main difference with the precipitated solid comes from the pre-exponential factor, which is nearly 3 orders of magnitude greater with a value of 2.5 x 10(12) s(-1). On the basis of these differences, we speculate that efficient rotational motion in the solvated crystals may take advantage of long-range lattice vibrations that couple with molecular modes and that the lack of long-range order may be responsible for the low pre-exponential factor observed in the disordered crystals.