A Reassessment of Sodium Correction Rates and Hospital Length of Stay Accounting for Admission Diagnosis.

Background: Recent studies have challenged assumptions about slow correction of severe hyponatremia and have shown that rapid correction is associated with shorter hospital length of stay. However, the confounding effect of admission diagnosis has not been fully explored. The objective of this study was to determine whether rapid correction is still associated with shorter length of stay when controlling for admission diagnosis. Methods: This retrospective cohort study is based on the Medical Information Mart for Intensive Care, including data from both MIMIC-III (2001-2012) and MIMIC-IV (2008-2019). Patients were identified who presented to the hospital with initial sodium <120 mEq/L and were categorized according to total sodium correction achieved in the first day (<6 mEq/L; 6-10 mEq/L; >10 mEq/L). Linear regression was used to assess for an association between correction rate and hospital length of stay, and to determine if this association was significant when controlling for admission diagnosis classifications based on diagnosis related groups (DRGs). Results: There were 636 patients included in this study. Median [IQR] hospital length of stay was 7 [4, 11] days. Patients had a median [IQR] initial sodium value of 117 [114, 118] mEq/L and final sodium value of 124 [119, 128] mEq/L. In a univariate linear regression, the highest rate of correction (>10 mEq/L) was associated with a shorter length of stay than a moderate rate of correction (coef. -2.363, 95% CI [-4.710, -0.017], p=0.048), but the association was not significant when controlling for admission diagnosis group (coef. -1.685, 95% CI [-3.836, 0.467], p=0.125). Conclusions: Faster sodium correction was not associated with shorter length of stay when controlling for admission diagnosis categories, suggesting that the disease state confounds this association. While some patients may be discharged earlier if sodium is corrected more rapidly, others may not benefit or may be harmed by this strategy.

A Retrospective Cohort Study of the Association of Inpatient Amlodipine Dose With Renal Complication Rates and Hospital Length of Stay.

Background Correct hospital medication reconciliation is important for continuity of care, but optimal home antihypertensive medication ordering has not been adequately studied. Since excessive hospital blood pressure control is associated with adverse renal and cardiovascular outcomes, we assessed the association of inpatient doses of amlodipine (10mg vs. 5mg) with length of stay and renal failure and fluid and electrolyte disorders (RF/FED). Methods In this retrospective cohort study, clinical and demographic data on patients not initially admitted to the ICU between 2008 and 2019 were extracted from the Medical Information Mart for Intensive Care (MIMIC-IV). Multivariable logistic regression was used to assess the association between amlodipine dose during the first 24 hours of admission and RF/FED. Multivariable linear regression was used to assess the association between amlodipine dose and length of stay when controlling for RF/FED or maximum blood urea nitrogen (BUN) concentration and other confounders. Results There were 5,932 patients included in this study, and 3,038 of whom received 10mg of amlodipine. A 10mg dose of amlodipine was associated with an increased likelihood of RF/FED (OR: 1.248, 95% CI (1.104, 1.412), p<0.001). It was also associated with a longer length of stay (coef.: 0.338, 95% CI (0.067, 0.609), p=0.015). This was not significant when controlling for RF/FED (dose coef.: 0.197, 95% CI (-0.070, 0.464), p=0.147) or maximum BUN (dose coef.: 0.082, 95% CI (-0.147, 0.312), p=0.482). Interpretation Higher amlodipine dose was associated with longer length of stay, and this is likely mediated by RF/FED. Randomized trials are needed to determine which home blood pressure medications should be ordered in the hospital.

Estimated GFR With Cystatin C and Creatinine in Clinical Practice: A Retrospective Cohort Study.

Rationale & Objective: Estimation of glomerular filtration rate (eGFR) and staging of chronic kidney disease (CKD) are essential to guide management. Although creatinine is routinely used, a recent national task force recommended the use of cystatin C for confirmation. The objective of this study was to examine the following parameters: (1) how cystatin C correlates with creatinine eGFR; (2) how it indicates differences in CKD staging; and (3) how it may affect kidney care delivery. Study Design: Retrospective observational cohort study. Setting & Participants: 1,783 inpatients and outpatients who had cystatin C and creatinine levels drawn within 24 hours at Brigham Health-affiliated clinical laboratories. Predictors: Serum creatinine levels, basic clinical/sociodemographic variables, and reasons for ordering cystatin C from a structured partial chart review. Analytical Approach: Univariate and multivariable linear and logistic regression. Results: Cystatin C-based eGFR was very strongly correlated with creatinine-based eGFR (Spearman correlation ρ = 0.83). Cystatin C eGFR resulted in a change to a later CKD stage in 27%, an earlier stage in 7%, and no change in 66% of patients. Black race was associated with a lower likelihood of change to a later stage (OR, 0.53; 95% CI [0.36, 0.75]; P < 0.001), whereas age (OR per year OR, 1.03; 95% CI [1.02, 1.04]; P < 0.001) and Elixhauser score (OR per point OR, 1.22; 95% CI [1.10, 1.36]; P < 0.001) were associated with a higher likelihood of change to a later stage. Limitations: Single center, no direct measurement of clearance for comparison, and inconsistent self-identification of race/ethnicity. Conclusions: Cystatin C eGFR correlates strongly with creatinine eGFR but can have a substantial effect on CKD staging. As cystatin C is adopted, clinicians must be informed on this impact.

Machine Learning for Acute Kidney Injury Prediction in the Intensive Care Unit.

Machine learning is the field of artificial intelligence in which computers are trained to make predictions or to identify patterns in data through complex mathematical algorithms. It has great potential in critical care to predict outcomes, such as acute kidney injury, and can be used for prognosis and to suggest management strategies. Machine learning can also be used as a research tool to advance our clinical and biochemical understanding of acute kidney injury. In this review, we introduce basic concepts in machine learning and review recent research in each of these domains.

Assessment of Racial and Ethnic Differences in Oxygen Supplementation Among Patients in the Intensive Care Unit.

Importance: Pulse oximetry (SpO2) is routinely used for transcutaneous monitoring of blood oxygenation, but it can overestimate actual oxygenation. This is more common in patients of racial and ethnic minority groups. The extent to which these discrepancies are associated with variations in treatment is not known. Objective: To determine if there are racial and ethnic disparities in supplemental oxygen administration associated with inconsistent pulse oximeter performance. Design, Setting, and Participants: This retrospective cohort study was based on the Medical Information Mart for Intensive Care (MIMIC)-IV critical care data set. Included patients were documented with a race and ethnicity as Asian, Black, Hispanic, or White and were admitted to the intensive care unit (ICU) for at least 12 hours before needing advanced respiratory support, if any. Oxygenation levels and nasal cannula flow rates for up to 5 days from ICU admission or until the time of intubation, noninvasive positive pressure ventilation, high-flow nasal cannula, or tracheostomy were analyzed. Main Outcomes and Measures: The primary outcome was time-weighted average supplemental oxygen rate. Covariates included race and ethnicity, sex, SpO2-hemoglobin oxygen saturation discrepancy, data duration, number and timing of blood gas tests on ICU days 1 to 3, partial pressure of carbon dioxide, hemoglobin level, average respiratory rate, Elixhauser comorbidity scores, and need for vasopressors or inotropes. Results: This cohort included 3069 patients (mean [SD] age, 66.9 [13.5] years; 83 were Asian, 207 were Black, 112 were Hispanic, 2667 were White). In a multivariable linear regression, Asian (coefficient, 0.602; 95% CI, 0.263 to 0.941; P = .001), Black (coefficient, 0.919; 95% CI, 0.698 to 1.140; P < .001), and Hispanic (coefficient, 0.622; 95% CI, 0.329 to 0.915; P < .001) race and ethnicity were all associated with a higher SpO2 for a given hemoglobin oxygen saturation. Asian (coefficient, -0.291; 95% CI, -0.546 to -0.035; P = .03), Black (coefficient, -0.294; 95% CI, -0.460 to -0.128; P = .001), and Hispanic (coefficient, -0.242; 95% CI, -0.463 to -0.020; P = .03) race and ethnicity were associated with lower average oxygen delivery rates. When controlling for the discrepancy between average SpO2 and average hemoglobin oxygen saturation, race and ethnicity were not associated with oxygen delivery rate. This discrepancy mediated the effect of race and ethnicity (-0.157; 95% CI, -0.250 to -0.057; P = .002). Conclusions and Relevance: In this cohort study, Asian, Black, and Hispanic patients received less supplemental oxygen than White patients, and this was associated with differences in pulse oximeter performance, which may contribute to known race and ethnicity-based disparities in care.

Ambient-pressure lignin valorization to high-performance polymers by intensified reductive catalytic deconstruction.

Chemocatalytic lignin valorization strategies are critical for a sustainable bioeconomy, as lignin, especially technical lignin, is one of the most available and underutilized aromatic feedstocks. Here, we provide the first report of an intensified reactive distillation­reductive catalytic deconstruction (RD-RCD) process to concurrently deconstruct technical lignins from diverse sources and purify the aromatic products at ambient pressure. We demonstrate the utility of RD-RCD bio-oils in high-performance additive manufacturing via stereolithography 3D printing and highlight its economic advantages over a conventional reductive catalytic fractionation/RCD process. As an example, our RD-RCD reduces the cost of producing a biobased pressure-sensitive adhesive from softwood Kraft lignin by up to 60% in comparison to the high-pressure RCD approach. Last, a facile screening method was developed to predict deconstruction yields using easy-to-obtain thermal decomposition data. This work presents an integrated lignin valorization approach for upgrading existing lignin streams toward the realization of economically viable biorefineries.

High resolution data modifies intensive care unit dialysis outcome predictions as compared with low resolution administrative data set.

High resolution clinical databases from electronic health records are increasingly being used in the field of health data science. Compared to traditional administrative databases and disease registries, these newer highly granular clinical datasets offer several advantages, including availability of detailed clinical information for machine learning and the ability to adjust for potential confounders in statistical models. The purpose of this study is to compare the analysis of the same clinical research question using an administrative database and an electronic health record database. The Nationwide Inpatient Sample (NIS) was used for the low-resolution model, and the eICU Collaborative Research Database (eICU) was used for the high-resolution model. A parallel cohort of patients admitted to the intensive care unit (ICU) with sepsis and requiring mechanical ventilation was extracted from each database. The primary outcome was mortality and the exposure of interest was the use of dialysis. In the low resolution model, after controlling for the covariates that are available, dialysis use was associated with an increased mortality (eICU: OR 2.07, 95% CI 1.75-2.44, p<0.01; NIS: OR 1.40, 95% CI 1.36-1.45, p<0.01). In the high-resolution model, after the addition of the clinical covariates, the harmful effect of dialysis on mortality was no longer significant (OR 1.04, 95% 0.85-1.28, p = 0.64). The results of this experiment show that the addition of high resolution clinical variables to statistical models significantly improves the ability to control for important confounders that are not available in administrative datasets. This suggests that the results from prior studies using low resolution data may be inaccurate and may need to be repeated using detailed clinical data.

Polyene-Free Photoluminescent Polymers via Hydrothermal Hydrolysis of Polyacrylonitrile in Neutral Water.

We report the hydrothermally enhanced hydrolysis of polyacrylonitrile (PAN) in neutral water, which generates photoluminescent polymers with low unsaturation degrees. Despite the hydrophobic nature of PAN, the product can be dissolved in water at a high concentration (≥100 g/L). The product exhibits complete absence of alkenes or aromatic structures, and photoluminescence originates from newly formed N- and O-containing groups. The presence of both n to π* and π to π* transitions is confirmed by time-dependent density functional theory (TD-DFT) calculations. The efficient transformation of PAN benefits from the enhanced hydrolysis of nitrile groups. While similar reactions have been reported previously under alkaline environments, we demonstrate that efficient hydrolysis can also occur in neutral water under the hydrothermal condition. Two additional methods based on different mechanisms are discussed to demonstrate the simplicity and efficiency of the hydrothermal reaction.

Heads up: don't forget the ordinary.

A 72-year-old woman presented to the emergency department with shortness of breath, diffuse swelling and a haemoglobin of 4.2 g/dl. Her history was notable for an unusual necrotic occipital neck mass that had begun to enlarge and intermittently bleed over the past year. The patient was initially unable to tolerate a CT scan because of the neck mass, and care was further complicated by extended boarding for more than 24 h in the emergency department. Initial fevers were attributed to blood transfusion, but she subsequently developed septic shock and disseminated intravascular coagulation from Escherichia coli bacteraemia, which led to anuric renal failure requiring haemodialysis. When the CT was performed, it revealed an obstructing ureteric stone which was the source of her infection, not the neck mass as had been assumed. This case underscores the importance of maintaining a broad and impartial differential diagnosis.

Immunoglobulin G subclass and antibody avidity responses in Malian children immunized with Plasmodium falciparum apical membrane antigen 1 vaccine candidate FMP2.1/AS02A.

BACKGROUND: A malaria vaccine based on Plasmodium falciparum apical membrane antigen 1 (AMA1) elicited strain specific efficacy in Malian children that waned in the second season after vaccination despite sustained AMA1 antibody titers. With the goal of identifying a humoral correlate of vaccine-induced protection, pre- and post-vaccination sera from children vaccinated with the AMA1 vaccine and from a control group that received a rabies vaccine were tested for AMA1-specific immunoglobulin G (IgG) subclasses (IgG1, IgG2, IgG3, and IgG4) and for antibody avidity. METHODS: Samples from a previously completed Phase 2 AMA1 vaccine trial in children residing in Mali, West Africa were used to determine AMA1-specific IgG subclass antibody titers and avidity by ELISA. Cox proportional hazards models were used to assess correlation between IgG subclass antibody titers and risk of time to first or only clinical malaria episode and risk of multiple episodes. Asexual P. falciparum parasite density measured for each child as area under the curve were used to assess correlation between IgG subclass antibody titers and parasite burden. RESULTS: AMA1 vaccination did not elicit a change in antibody avidity; however, AMA1 vaccinees had a robust IgG subclass response that persisted over the malaria transmission season. AMA1-specific IgG subclass responses were not associated with decreased risk of subsequent clinical malaria. For the AMA1 vaccine group, IgG3 levels at study day 90 correlated with high parasite burden during days 90-240. In the control group, AMA1-specific IgG subclass rise and persistence over the malaria season was modest and correlated with age. In the control group, titers of several IgG subclasses at days 90 and 240 correlated with parasite burden over the first 90 study days, and IgG3 at day 240 correlated with parasite burden during days 90-240. CONCLUSIONS: Neither IgG subclass nor avidity was associated with the modest, strain-specific efficacy elicited by this blood stage malaria vaccine. Although a correlate of protection was not identified, correlations between subclass titers and age, and correlations between IgG subclass titers and parasite burden, defined by area under the curve parasitaemia levels, were observed, which expand knowledge about IgG subclass responses. IgG3, known to have the shortest half-life of the IgG subclasses, might be the most temporally relevant indicator of ongoing malaria exposure when examining antibody responses to AMA1.

Polymer-Based Synthetic Routes to Carbon-Based Metal-Free Catalysts.

Carbons are increasingly important as possible alternatives to expensive metal catalysts owing to the wide range of chemical properties they can exhibit and the growing set of synthetic routes available to produce them. This progress report discusses the process of making catalytic carbons from polymeric precursors, focusing on mechanisms of carbonization and how the polymer structures and synthetic procedures affect the resulting carbons. In considering what is necessary to move laboratory catalytic carbons to industrial and commercial applications, the cost and complexity to produce them are a considerable challenge to overcome. Industrially produced carbons are typically made from biopolymers such as lignin while many of the catalytic carbons studied in literature are from synthetic polymers. Thus, studying polymer-derived carbons can provide insights into the carbonization process and the properties of catalytic carbons, which can subsequently be translated to improve biopolymer-derived carbons in an economical way. Aspects of polymer carbonization discussed include carbonization mechanisms, effects of crosslinkers, polymer microstructure, heteroatom control, and effects of nanostructuring.

Comparison of analogue and electronic stethoscopes for pulmonary auscultation by internal medicine residents.

BACKGROUND: Electronic stethoscopes are becoming more common in clinical practice. They may improve the accuracy and efficiency of pulmonary auscultation, but the data to support their benefit are limited. OBJECTIVE: To determine how auscultation with an electronic stethoscope may affect clinical decision making. METHODS: An online module consisting of six fictional ambulatory cases was developed. Each case included a brief history and lung sounds recorded with an analogue and electronic stethoscope. Internal medicine resident participants were randomly selected to hear either the analogue or electronic lung sounds. Numbers of correct answers, time spent on each case and numbers of times the recordings were played were compared between the groups who heard each mode of auscultation, with a p value of less than 0.05 indicating statistical significance. RESULTS: 61 internal medicine residents completed at least one case, and 41 residents completed all six cases. There were no significant differences in overall scores between participants who heard analogue and electronic lung sounds (3.14±0.10 out of 6 correct for analogue, 3.20±0.10 out of 6 for electronic, p=0.74). There were no significant differences in performance for any of the six cases (p=0.78), time spent on the cases (p=0.67) or numbers of times the recordings were played (p=0.85). CONCLUSION: When lung sounds were amplified with an electronic stethoscope, we did not detect an effect on performance, time spent on the cases or numbers of times participants listened to the recordings.

Effects of cigarette smoke on pulmonary endothelial cells.

Cigarette smoking is the leading cause of preventable disease and death in the United States. Cardiovascular comorbidities associated with both active and secondhand cigarette smoking indicate the vascular toxicity of smoke exposure. Growing evidence supports the injurious effect of cigarette smoke on pulmonary endothelial cells and the roles of endothelial cell injury in development of acute respiratory distress syndrome (ARDS), emphysema, and pulmonary hypertension. This review summarizes results from studies of humans, preclinical animal models, and cultured endothelial cells that document toxicities of cigarette smoke exposure on pulmonary endothelial cell functions, including barrier dysfunction, endothelial activation and inflammation, apoptosis, and vasoactive mediator production. The discussion is focused on effects of cigarette smoke-induced endothelial injury in the development of ARDS, emphysema, and vascular remodeling in chronic obstructive pulmonary disease.

Osteoconductive Enhancement of Polyether Ether Ketone: A Mild Covalent Surface Modification Approach.

Polyether ether ketone (PEEK, 1) is an important material for the fabrication of implants employed in spinal fusion surgery. Although its radiolucency and favorable elastic modulus have made PEEK an attractive choice for interbody fusion devices, its poor osseointegrative properties prevent the formation of a strong union between implant and surrounding bone structures and remain a major liability. Recent advancements in PEEK surface technology have resulted in improved osseointegration; however, the identification of an ideal implant material has proven challenging. In this manuscript, we describe our preliminary investigation into the realm of PEEK-based fusion devices that has culminated in the discovery of a mild, solution-based process for the preparation of covalently surface modified PEEK biomaterials that display enhanced osteoconductive properties. Surface modification occurred under mild reaction conditions via the acid-mediated addition of various commercially available hydrophilic oxyamine and hydrazine nucleophiles to the diaryl ketone moiety of PEEK. The resulting modified surfaces have been confirmed by contact angle measurements and X-ray photoelectron spectroscopy (XPS). Subsequent in vitro studies demonstrated the enhanced capability of several modified PEEK variants to promote osteogenic differentiation and mineralized calcium deposition relative to unmodified PEEK surfaces.

Individual Nanoporous Carbon Spheres with High Nitrogen Content from Polyacrylonitrile Nanoparticles with Sacrificial Protective Layers.

Functional nanoporous carbon spheres (NPC-S) are important for applications ranging from adsorption, catalysis, separation to energy storage, and biomedicine. The development of effective NPC-S materials has been hindered by the fusion of particles during the pyrolytic process that results in agglomerated materials with reduced activity. Herein, we present a process that enables the scalable synthesis of dispersed NPC-S materials by coating sacrificial protective layers around polyacrylonitrile nanoparticles (PAN NPs) to prevent interparticle cross-linking during carbonization. In a first step, PAN NPs are synthesized using miniemulsion polymerization, followed by grafting of 3-(triethoxysilyl)propyl methacrylate (TESPMA) to form well-defined core-shell structured PAN@PTESPMA nanospheres. The cross-linked PTESPMA brush layer suppresses cross-linking reactions during carbonization. Uniform NPC-S exhibiting diameters of ∼100 nm, with relatively high accessible surface area (∼424 m2/g), and high nitrogen content (14.8 wt %) was obtained. When compared to a regular nanoporous carbon monolith (NPC-M), the nitrogen-doped NPC-S demonstrated better performance for CO2 capture with a higher CO2/N2 selectivity, an increased efficiency in catalytic oxygen reduction reactions, as well as improved electrochemical capacitive behavior. This miniemulsion polymerization-based strategy for the preparation of functional PAN NPs provides a new, facile approach to prepare high-performance porous carbon spheres for diverse applications.

Gold Nanoclusters Promote Electrocatalytic Water Oxidation at the Nanocluster/CoSe2 Interface.

Electrocatalytic water splitting to produce hydrogen comprises the hydrogen and oxygen evolution half reactions (HER and OER), with the latter as the bottleneck process. Thus, enhancing the OER performance and understanding the mechanism are critically important. Herein, we report a strategy for OER enhancement by utilizing gold nanoclusters to form cluster/CoSe2 composites; the latter exhibit largely enhanced OER activity in alkaline solutions. The Au25/CoSe2 composite affords a current density of 10 mA cm-2 at small overpotential of ∼0.43 V (cf. CoSe2: ∼0.52 V). The ligand and gold cluster size can also tune the catalytic performance of the composites. Based upon XPS analysis and DFT simulations, we attribute the activity enhancement to electronic interactions between nanocluster and CoSe2, which favors the formation of the important intermediate (OOH) as well as the desorption of oxygen molecules over Aun/CoSe2 composites in the process of water oxidation. Such an atomic level understanding may provide some guidelines for design of OER catalysts.

Electrochemically Mediated Reversible Addition-Fragmentation Chain-Transfer Polymerization.

An electrochemically mediated reversible addition-fragmentation chain-transfer polymerization (eRAFT) of (meth)acrylates was successfully carried out via electroreduction of either benzoyl peroxide (BPO) or 4-bromobenzenediazonium tetrafluoroborate (BrPhN2+) which formed aryl radicals, acting as initiators for RAFT polymerization. Direct electroreduction of chain transfer agents was unsuccessful since it resulted in the formation of carbanions by a two-electron transfer process. Reduction of BrPhN2+ under a fixed potential showed acceptable control, but limited conversion due to the generation of a passivating organic layer grafted on the working electrode surface. However, using fixed current conditions, easier to implement than fixed potential conditions, conversions > 80% were achieved. Well-defined homopolymers and block copolymers with a broad range of targeted degrees of polymerization were prepared.