Peripartum patient with epigastric pain

A 44-year-old female, gravida 2, para 1, abortus 1, presented to the emergency department with epigastric pain, vomiting and nosebleed at 36 weeks gestation. She had right upper quadrant tenderness and was hypertensive at 138/90 mmHg. Laboratory studies demonstrated decreased platelets of 122 k/mcL, Hb of 11.2 g/dL and RBC of 3.48 M/mcL, elevated AST of 371 U/L and ALT of 522 U/L, and proteinuria of 13 mg/dL

Promoting microbial utilization of phenolic substrates from bio-oil

The economic viability of the biorefinery concept is limited by the valorization of lignin. One possible method of lignin valorization is biological upgrading with aromatic-catabolic microbes. In conjunction, lignin monomers can be produced by fast pyrolysis and fractionation. However, biological upgrading of these lignin monomers is limited by low water solubility. Here, we address the problem of low water solubility with an emulsifier blend containing approximately 70 wt% Tween® 20 and 30 wt% Span® 80. Pseudomonas putida KT2440 grew to an optical density (OD600) of 1.0 ± 0.2 when supplied with 1.6 wt% emulsified phenolic monomer-rich product produced by fast pyrolysis of red oak using an emulsifier dose of 0.076 ± 0.002 g emulsifier blend per g of phenolic monomer-rich product. This approach partially mitigated the toxicity of the model phenolic monomer p-coumarate to the microbe, but not benzoate or vanillin. This study provides a proof of concept that processing of biomass-derived phenolics to increase aqueous availability can enhance microbial utilization

Correlation between subcutaneous knee fat thickness and chondromalacia patellae on magnetic resonance imaging of the knee

AbstractPurposeChondromalacia patellae is a common cause of anterior knee pain in young patients and can be detected noninvasively with magnetic resonance imaging (MRI). The purpose of our study was to evaluate the correlation between subcutaneous fat thickness around the knee joint on axial MRIs as a surrogate marker of obesity, with the presence or absence of chondromalacia patellae.MethodsA retrospective review was conducted of knee MRIs in 170 patients who satisfied the inclusion criteria. Imaging was performed over a 12-month period on a 1.5T MRI system with a dedicated extremity coil. Two radiologists experienced in musculoskeletal imaging assessed each examination in consensus for the presence or absence of chondromalacia patellae and graded positive studies from 0 (absent) to 3 (full cartilage thickness defect). Measurement of subcutaneous knee fat thickness was obtained on the medial aspect of the knee.ResultsMRI findings of chondromalacia patellae were present in 33 patients (19.4%), of which, there were 11 grade 1 lesions (33.3%), 9 grade 2 lesions (27.3%), and 13 grade 3 lesions (39.4%). The mean subcutaneous knee fat thickness was significantly higher in the chondromalacia patellae group for all grades compared with the normal group (P < .001), and there was a significant correlation between subcutaneous knee fat thickness and grades of chondromalacia patellae (R = 0.48 [95% confidence interval, 0.38-0.68]; P < .001). Female patients had thicker subcutaneous knee fat and more severe grades of chondromalacia patellae.ConclusionSubcutaneous knee fat thickness as a surrogate marker of obesity was positively associated with the presence and severity of chondromalacia patellae on MRI

Promoting microbial utilization of phenolic substrates from bio-oil

The economic viability of the biorefinery concept is limited by the valorization of lignin. One possible method of lignin valorization is biological upgrading with aromatic-catabolic microbes. In conjunction, lignin monomers can be produced by fast pyrolysis and fractionation. However, biological upgrading of these lignin monomers is limited by low water solubility. Here, we address the problem of low water solubility with an emulsifier blend containing approximately 70 wt% Tween® 20 and 30 wt% Span® 80. Pseudomonas putida KT2440 grew to an optical density (OD600) of 1.0 ± 0.2 when supplied with 1.6 wt% emulsified phenolic monomer-rich product produced by fast pyrolysis of red oak using an emulsifier dose of 0.076 ± 0.002 g emulsifier blend per g of phenolic monomer-rich product. This approach partially mitigated the toxicity of the model phenolic monomer p-coumarate to the microbe, but not benzoate or vanillin. This study provides a proof of concept that processing of biomass-derived phenolics to increase aqueous availability can enhance microbial utilization.This is a manuscript of an article published as Davis, Kirsten, Marjorie R. Rover, Davinia Salvachúa, Ryan G. Smith, Gregg T. Beckham, Zhiyou Wen, Robert C. Brown, and Laura R. Jarboe. "Promoting microbial utilization of phenolic substrates from bio-oil." Journal of Industrial Microbiology & Biotechnology (2019). DOI: 10.1007/s10295-019-02208-z. Posted with permission.</p

The Techno-Economic Basis for Coproduct Manufacturing To Enable Hydrocarbon Fuel Production from Lignocellulosic Biomass

Biorefinery process development relies on techno-economic analysis (TEA) to identify primary cost drivers, prioritize research directions, and mitigate technical risk for scale-up through development of detailed process designs. Here, we conduct TEA of a model 2000 dry metric ton-per-day lignocellulosic biorefinery that employs a two-step pretreatment and enzymatic hydrolysis to produce biomass-derived sugars, followed by biological lipid production, lipid recovery, and catalytic hydrotreating to produce renewable diesel blendstock (RDB). On the basis of projected near-term technical feasibility of these steps, we predict that RDB could be produced at a minimum fuel selling price (MFSP) of USD $9.55/gasoline-gallon-equivalent (GGE), predicated on the need for improvements in the lipid productivity and yield beyond current benchmark performance. This cost is significant given the limitations in scale and high costs for aerobic cultivation of oleaginous microbes and subsequent lipid extraction/recovery. In light of this predicted cost, we developed an alternative pathway which demonstrates that RDB costs could be substantially reduced in the near term if upgradeable fractions of biomass, in this case hemicellulose-derived sugars, are diverted to coproducts of sufficient value and market size; here, we use succinic acid as an example coproduct. The coproduction model predicts an MFSP of USD$5.28/GGE when leaving conversion and yield parameters unchanged for the fuel production pathway, leading to a change in biorefinery RDB capacity from 24 to 15 MM GGE/year and 0.13 MM tons of succinic acid per year. Additional analysis demonstrates that beyond the near-term projections assumed in the models here, further reductions in the MFSP toward $2–3/GGE (which would be competitive with fossil-based hydrocarbon fuels) are possible with additional transformational improvements in the fuel and coproduct trains, especially in terms of carbon efficiency to both fuels and coproducts, recovery and purification of fuels and coproducts, and coproduct selection and price. Overall, this analysis documents potential economics for both a hydrocarbon fuel and bioproduct process pathway and highlights prioritized research directions beyond the current benchmark to enable hydrocarbon fuel production via an oleaginous microbial platform with simultaneous coproduct manufacturing from lignocellulosic biomass

Research considerations for prospective studies of patients with coma and disorders of consciousness

Disorders of consciousness are neurological conditions characterized by impaired arousal and awareness of self and environment. Behavioural responses are absent or are present but fluctuate. Disorders of consciousness are commonly encountered as a consequence of both acute and chronic brain injuries, yet reliable epidemiological estimates would require inclusive, operational definitions of the concept, as well as wider knowledge dissemination among involved professionals. Whereas several manifestations have been described, including coma, vegetative state/unresponsive wakefulness syndrome and minimally conscious state, a comprehensive neurobiological definition for disorders of consciousness is still lacking. The scientific literature is primarily observational, and studies-specific aetiologies lead to disorders of consciousness. Despite advances in these disease-related forms, there remains uncertainty about whether disorders of consciousness are a disease-agnostic unitary entity with a common mechanism, prognosis or treatment response paradigm. Our knowledge of disorders of consciousness has also been hampered by heterogeneity of study designs, variables, and outcomes, leading to results that are not comparable for evidence synthesis. The different backgrounds of professionals caring for patients with disorders of consciousness and the different goals at different stages of care could partly explain this variability. The Prospective Studies working group of the Neurocritical Care Society Curing Coma Campaign was established to create a platform for observational studies and future clinical trials on disorders of consciousness and coma across the continuum of care. In this narrative review, the author panel presents limitations of prior observational clinical research and outlines practical considerations for future investigations. A narrative review format was selected to ensure that the full breadth of study design considerations could be addressed and to facilitate a future consensus-based statement (e.g. via a modified Delphi) and series of recommendations. The panel convened weekly online meetings from October 2021 to December 2022. Research considerations addressed the nosographic status of disorders of consciousness, case ascertainment and verification, selection of dependent variables, choice of covariates and measurement and analysis of outcomes and covariates, aiming to promote more homogeneous designs and practices in future observational studies. The goal of this review is to inform a broad community of professionals with different backgrounds and clinical interests to address the methodological challenges imposed by the transition of care from acute to chronic stages and to streamline data gathering for patients with disorders of consciousness. A coordinated effort will be a key to allow reliable observational data synthesis and epidemiological estimates and ultimately inform condition-modifying clinical trials

Research considerations for prospective studies of patients with coma and disorders of consciousness

Disorders of consciousness are neurological conditions characterized by impaired arousal and awareness of self and environment. Behavioural responses are absent or are present but fluctuate. Disorders of consciousness are commonly encountered as a consequence of both acute and chronic brain injuries, yet reliable epidemiological estimates would require inclusive, operational definitions of the concept, as well as wider knowledge dissemination among involved professionals. Whereas several manifestations have been described, including coma, vegetative state/unresponsive wakefulness syndrome and minimally conscious state, a comprehensive neurobiological definition for disorders of consciousness is still lacking. The scientific literature is primarily observational, and studies-specific aetiologies lead to disorders of consciousness. Despite advances in these disease-related forms, there remains uncertainty about whether disorders of consciousness are a disease-agnostic unitary entity with a common mechanism, prognosis or treatment response paradigm. Our knowledge of disorders of consciousness has also been hampered by heterogeneity of study designs, variables, and outcomes, leading to results that are not comparable for evidence synthesis. The different backgrounds of professionals caring for patients with disorders of consciousness and the different goals at different stages of care could partly explain this variability. The Prospective Studies working group of the Neurocritical Care Society Curing Coma Campaign was established to create a platform for observational studies and future clinical trials on disorders of consciousness and coma across the continuum of care. In this narrative review, the author panel presents limitations of prior observational clinical research and outlines practical considerations for future investigations. A narrative review format was selected to ensure that the full breadth of study design considerations could be addressed and to facilitate a future consensus-based statement (e.g. via a modified Delphi) and series of recommendations. The panel convened weekly online meetings from October 2021 to December 2022. Research considerations addressed the nosographic status of disorders of consciousness, case ascertainment and verification, selection of dependent variables, choice of covariates and measurement and analysis of outcomes and covariates, aiming to promote more homogeneous designs and practices in future observational studies. The goal of this review is to inform a broad community of professionals with different backgrounds and clinical interests to address the methodological challenges imposed by the transition of care from acute to chronic stages and to streamline data gathering for patients with disorders of consciousness. A coordinated effort will be a key to allow reliable observational data synthesis and epidemiological estimates and ultimately inform condition-modifying clinical trials

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

BackgroundMultisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments.MethodsThe Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370.FindingsWe enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2-11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75-1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58-1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91-1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70-1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11-0·20]; p&lt;0·0001) and glucocorticoids alone (0·68 [0·50-0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38-0·67]; p&lt;0·0001) or glucocorticoids alone (0·63 [0·45-0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups.InterpretationRecovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries.FundingImperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health