G-CSF drives autoinflammation in APLAID.

Missense mutations in PLCG2 can cause autoinflammation with phospholipase C gamma 2-associated antibody deficiency and immune dysregulation (APLAID). Here, we generated a mouse model carrying an APLAID mutation (p.Ser707Tyr) and found that inflammatory infiltrates in the skin and lungs were only partially ameliorated by removing inflammasome function via the deletion of caspase-1. Also, deleting interleukin-6 or tumor necrosis factor did not fully prevent APLAID mutant mice from autoinflammation. Overall, these findings are in accordance with the poor response individuals with APLAID have to treatments that block interleukin-1, JAK1/2 or tumor necrosis factor. Cytokine analysis revealed increased granulocyte colony-stimulating factor (G-CSF) levels as the most distinct feature in mice and individuals with APLAID. Remarkably, treatment with a G-CSF antibody completely reversed established disease in APLAID mice. Furthermore, excessive myelopoiesis was normalized and lymphocyte numbers rebounded. APLAID mice were also fully rescued by bone marrow transplantation from healthy donors, associated with reduced G-CSF production, predominantly from non-hematopoietic cells. In summary, we identify APLAID as a G-CSF-driven autoinflammatory disease, for which targeted therapy is feasible.

Germline NLRP1 Mutations Cause Skin Inflammatory and Cancer Susceptibility Syndromes via Inflammasome Activation.

Inflammasome complexes function as key innate immune effectors that trigger inflammation in response to pathogen- and danger-associated signals. Here, we report that germline mutations in the inflammasome sensor NLRP1 cause two overlapping skin disorders: multiple self-healing palmoplantar carcinoma (MSPC) and familial keratosis lichenoides chronica (FKLC). We find that NLRP1 is the most prominent inflammasome sensor in human skin, and all pathogenic NLRP1 mutations are gain-of-function alleles that predispose to inflammasome activation. Mechanistically, NLRP1 mutations lead to increased self-oligomerization by disrupting the PYD and LRR domains, which are essential in maintaining NLRP1 as an inactive monomer. Primary keratinocytes from patients experience spontaneous inflammasome activation and paracrine IL-1 signaling, which is sufficient to cause skin inflammation and epidermal hyperplasia. Our findings establish a group of non-fever inflammasome disorders, uncover an unexpected auto-inhibitory function for the pyrin domain, and provide the first genetic evidence linking NLRP1 to skin inflammatory syndromes and skin cancer predisposition.

SIDT2 Transports Extracellular dsRNA into the Cytoplasm for Innate Immune Recognition.

Double-stranded RNA (dsRNA) is a common by-product of viral infections and acts as a potent trigger of antiviral immunity. In the nematode C. elegans, sid-1 encodes a dsRNA transporter that is highly conserved throughout animal evolution, but the physiological role of SID-1 and its orthologs remains unclear. Here, we show that the mammalian SID-1 ortholog, SIDT2, is required to transport internalized extracellular dsRNA from endocytic compartments into the cytoplasm for immune activation. Sidt2-deficient mice exposed to extracellular dsRNA, encephalomyocarditis virus (EMCV), and herpes simplex virus 1 (HSV-1) show impaired production of antiviral cytokines and-in the case of EMCV and HSV-1-reduced survival. Thus, SIDT2 has retained the dsRNA transport activity of its C. elegans ortholog, and this transport is important for antiviral immunity.

Holocene variations in Lake Titicaca water level and their implications for sociopolitical developments in the central Andes.

Holocene climate in the high tropical Andes was characterized by both gradual and abrupt changes, which disrupted the hydrological cycle and impacted landscapes and societies. High-resolution paleoenvironmental records are essential to contextualize archaeological data and to evaluate the sociopolitical response of ancient societies to environmental variability. Middle-to-Late Holocene water levels in Lake Titicaca were reevaluated through a transfer function model based on measurements of organic carbon stable isotopes, combined with high-resolution profiles of other geochemical variables and paleoshoreline indicators. Our reconstruction indicates that following a prolonged low stand during the Middle Holocene (4000 to 2400 BCE), lake level rose rapidly ~15 m by 1800 BCE, and then increased another 3 to 6 m in a series of steps, attaining the highest values after ~1600 CE. The largest lake-level increases coincided with major sociopolitical changes reported by archaeologists. In particular, at the end of the Formative Period (500 CE), a major lake-level rise inundated large shoreline areas and forced populations to migrate to higher elevation, likely contributing to the emergence of the Tiwanaku culture.

Posttranslational Modification as a Critical Determinant of Cytoplasmic Innate Immune Recognition.

Cell surface innate immune receptors can directly detect a variety of extracellular pathogens to which cytoplasmic innate immune sensors are rarely exposed. Instead, within the cytoplasm, the environment is rife with cellular machinery and signaling pathways that are indirectly perturbed by pathogenic microbes to activate intracellular sensors, such as pyrin, NLRP1, NLRP3, or NLRC4. Therefore, subtle changes in key intracellular processes such as phosphorylation, ubiquitination, and other pathways leading to posttranslational protein modification are key determinants of innate immune recognition in the cytoplasm. This concept is critical to establish the "guard hypothesis" whereby otherwise homeostatic pathways that keep innate immune sensors at bay are released in response to alterations in their posttranslational modification status. Originally identified in plants, evidence that a similar guardlike mechanism exists in humans has recently been identified, whereby a mutation that prevents phosphorylation of the innate immune sensor pyrin triggers a dominantly inherited autoinflammatory disease. It is also noteworthy that even when a cytoplasmic innate immune sensor has a direct ligand, such as bacterial peptidoglycan (NOD1 or NOD2), RNA (RIG-I or MDA5), or DNA (cGAS or IFI16), it can still be influenced by posttranslational modification to dramatically alter its response. Therefore, due to their existence in the cytoplasmic milieu, posttranslational modification is a key determinant of intracellular innate immune receptor functionality.

Pyrin variant E148Q potentiates inflammasome activation and the effect of pathogenic mutations in cis.

OBJECTIVE: The p.E148Q variant in pyrin is present in different populations at a frequency of up to 29%, and has been associated with diseases, including vasculitis and FMF. The pathogenicity of p.E148Q in FMF is unclear, even when observed in cis or in trans to a single, typically recessive, pathogenic mutation. We performed functional validation to determine whether p.E148Q increases the ability of pyrin to form an active inflammasome complex in cell lines. METHODS: We interrogated the Australian Autoinflammatory Disease RegistrY (AADRY) to find candidate inheritance patterns for the p.E148Q variant in pyrin. Different pyrin variant combinations were tested in HEK293T cells stably expressing the adaptor protein apoptosis-associated speck-like (ASC), which were analysed by flow cytometry to visualize inflammasome formation, with and without stimulation by Clostridioides difficile toxin B (TcdB). Inflammasome-dependent cytokine secretion was also quantified by ELISA of supernatants from THP-1 cells transduced with lentiviral expression vectors. RESULTS: In AADRY, we observed the p.E148Q allele in individuals with autoinflammatory diseases alone or in conjunction with other pyrin variants. Two FMF families harboured the allele p.E148Q-M694I in cis with dominant heritability. In vitro, p.E148Q pyrin could spontaneously potentiate inflammasome formation, with increased IL-1ß and IL-18 secretion. p.E148Q in cis to classical FMF mutations provided significant potentiation of inflammasome formation. CONCLUSION: The p.E148Q variant in pyrin potentiates inflammasome activation in vitro. In cis, this effect is additive to known pathogenic FMF mutations. In some families, this increased effect could explain why FMF segregates as an apparently dominant disease.

Paediatric emergency front-of-neck airway: issues of ethics, law, and philosophy.

Practitioners can face significant challenges when managing the airways of infants and neonates because of their unique anatomical and physiological features. The requirement for emergency airway management in this age group is rare. Details of emergency airway techniques in paediatric practice guidelines are missing or lack consensus, and it is known that outcomes for affected children can be poor. Ideally, these children should be managed by experienced paediatric airway practitioners working in a team. However, situations can arise where practitioners, unfamiliar and inexperienced with infants, find themselves in charge. So, what happens when such a practitioner encounters this life-or-death scenario and feels ill-equipped to act? The ethical and legal issues surrounding the management of this emergency are clearly defined, but they can be unknown or misunderstood by doctors. Compounding the extreme stress of the scenario is the moral and ethical dilemma of whether to act or not. The following discussion explores these issues and examines the philosophical and psychological perspectives.

Hinge prostheses in the revision of unicompartmental knee replacement: a descriptive analysis of data from the national joint registry for England, Wales and Northern Ireland.

INTRODUCTION: Unicompartmental knee replacement (UKR) is an effective surgical strategy in patients with isolated medial or lateral compartment osteoarthritis. Study aims were to (1) describe the epidemiology of patients undergoing revision of UKR to a hinge knee replacement (HKR); (2) identify factors influencing time to revision; (3) evaluate HKR survival. MATERIALS AND METHODS: An analysis of National Joint Registry data was undertaken, exploring revision of UKR to HKR between 2007 and April 2021. Descriptive analysis of eligible patients and Cox Regression to identify key determinants of time to revision were performed. Failure of HKR post-revision was assessed using survival analysis. RESULTS: 111 patients underwent revision of UKR to HKR. Median age at revision was 70 years and most common indications were instability (n = 42) and infection (n = 22). The most common implant was a rotating HKR. Significant independent factors associated with earlier revision were periprosthetic fracture (p = 0.03) and malalignment (p = 0.03). Progressive osteoarthritis (p = 0.01) and higher ASA grades (3: p = 0.01, 4: p < 0.01) delayed time to revision; patient sex and age were not significant factors. Ten patients required subsequent re-revision; median age at re-revision was 61 years. HKR revised from UKR had an 89.3% revision-free risk at 5 years. Male sex (p < 0.01) and younger age (p < 0.01) were associated with re-revision. CONCLUSIONS: Factors associated with time to revision may be used to counsel patients prior to UKR. The survivorship of the HKR of 89.3% at 5 years is concerning and careful consideration should be given when using this level of constraint when revising UKR in younger or male patients.

The left ventricular assist device: a literature review and guidelines for dental care.

About 6.2 million adults in the United States suffer from heart failure (HF). For patients with advanced HF refractory to medical therapy, an orthotopic heart transplant or a ventricular assist device (VAD) is the only long-term survival option. The most commonly used form of these devices is the left VAD (LVAD), implanted to support the left ventricle. As many as 2754 LVADs were implanted annually between 2006 and 2015, allowing recipients to maintain a relatively normal lifestyle, including both elective and emergency dental care in the ambulatory setting. As more LVADs are implanted, oral healthcare providers (OHCPs) are more likely to encounter these patients in an outpatient clinical setting. This study aims to educate OHCPs on the specific needs of these patients and to begin development of clinical guidelines for their dental management. A literature review using electronic resources was conducted to identify all literature relevant to the clinical topic. Appropriate literature was selected based on established inclusion and exclusion criteria, and 3 articles published between 2015 and 2020 were identified. None offered clinical practice guidelines for the care of patients with implanted LVADs. However, it is known that patients supported by an LVAD are at higher risk of thrombotic complications, which can lead to pump system failure and embolic stroke. To reduce the risk of complications, these patients are treated with anticoagulation therapy. Interruption of these drugs prior to dental treatment is not recommended. Due to the side effects of anticoagulation therapy and acquired coagulopathy, patients with an LVAD are also at increased risk of bleeding events. Thus, perioperative hemorrhagic risk during routine oral surgical procedures must be considered. While most dental care can be done in an outpatient setting, OHCPs should be aware of the special needs of these patients and provide appropriate care through close coordination with the LVAD/transplant team.

Endogenous and Therapeutic 25-Hydroxycholesterols May Worsen Early SARS-CoV-2 Pathogenesis in Mice.

Oxysterols (i.e., oxidized cholesterol species) have complex roles in biology. 25-Hydroxycholesterol (25HC), a product of the activity of cholesterol-25-hydroxylase (CH25H) on cholesterol, has recently been shown to be broadly antiviral, suggesting therapeutic potential against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, 25HC can also amplify inflammation and be converted by CYP7B1 (cytochrome P450 family 7 subfamily B member 1) to 7α,25-dihydroxycholesterol, a lipid with chemoattractant activity, via the G protein-coupled receptor EBI2 (Epstein-Barr virus-induced gene 2)/GPR183 (G protein-coupled receptor 183). Here, using in vitro studies and two different murine models of SARS-CoV-2 infection, we investigate the effects of these two oxysterols on SARS-CoV-2 pneumonia. We show that although 25HC and enantiomeric-25HC are antiviral in vitro against human endemic coronavirus-229E, they did not inhibit SARS-CoV-2; nor did supplemental 25HC reduce pulmonary SARS-CoV-2 titers in the K18-human ACE2 (angiotensin-converting enzyme 2) mouse model in vivo. Treatment with 25HC also did not alter immune cell influx into the airway, airspace cytokines, lung pathology, weight loss, symptoms, or survival but was associated with increased airspace albumin, an indicator of microvascular injury, and increased plasma proinflammatory cytokines. Conversely, mice treated with the EBI2/GPR183 inhibitor NIBR189 displayed a modest increase in lung viral load only at late time points but no change in weight loss. Consistent with these findings, although Ch25h and 25HC were upregulated in the lungs of SARS-CoV-2-infected wild-type mice, lung viral titers and weight loss in Ch25h-/- and Gpr183-/- mice infected with the ß variant were similar to those in control animals. Taken together, endogenous 25HCs do not significantly regulate early SARS-CoV-2 replication or pathogenesis, and supplemental 25HC may have proinjury rather than therapeutic effects in SARS-CoV-2 pneumonia.

Damming the rivers of the Amazon basin.

More than a hundred hydropower dams have already been built in the Amazon basin and numerous proposals for further dam constructions are under consideration. The accumulated negative environmental effects of existing dams and proposed dams, if constructed, will trigger massive hydrophysical and biotic disturbances that will affect the Amazon basin's floodplains, estuary and sediment plume. We introduce a Dam Environmental Vulnerability Index to quantify the current and potential impacts of dams in the basin. The scale of foreseeable environmental degradation indicates the need for collective action among nations and states to avoid cumulative, far-reaching impacts. We suggest institutional innovations to assess and avoid the likely impoverishment of Amazon rivers.

The impact of Longitudinal Integrated Foundation Training: preliminary experiences in the United Kingdom.

BACKGROUND: The United Kingdom health system is challenged with retaining doctors entering specialty training directly after their second foundation year. Improving doctors' training experience during the foundation programme may aid such retention. The Longitudinal Integrated Foundation Training (LIFT) pilot scheme aimed to provide a programme that improves the quality of their foundation training experience, advance patient-centred care and provide doctors with more experience in the primary care settings. METHODS: During this pilot study, three methods were employed to evaluate and compare doctors' experiences across their 2-year foundation training programme: Horus ePortfolio assessment of six domains for good medical practice analysed using a T-test, online survey assessments analysed using a 2-tailed chi-square test, and focus group feedback sessions with thematic analysis. RESULTS: Doctors completing LIFT (n = 47) scored a higher but non-significant mean score on all six domains for good medical practice versus doctors completing traditional foundation training (n = 94). By the end of foundation training, 100% of LIFT doctors rated their understanding of how primary and secondary care work together as high versus 78.7% of traditional doctors (p < 0.05). Improvements in wellbeing were observed among LIFT doctors, along with a reduction in the proportion of doctors considering leaving medical training. A significantly greater number of LIFT doctors versus traditional doctors rated their compassion for patients as high (100% versus 86.8%; p < 0.05), intended to become general practitioners (23.1% versus 13.5%; p < 0.05) and rated the extent to which they felt well informed and able to consider a general practice career rather than a hospital career as high (91.7% versus 72.3%, respectively; p < 0.05). Some LIFT doctors felt they had reduced exposure to secondary care, received less on-call experience and considered working a half-day to be problematic; challenges ameliorated by the end of the 2-year foundation programme. CONCLUSION: The LIFT programme enhanced the quality of foundation training and improved doctors' experiences and competencies, generating valuable insights for the future of education and healthcare delivery. Applying the principles of LIFT to foundation training helps doctors to be more compassionate and patient-centred, leading to enhanced individualised patient care.

Unrecognised oesophageal intubation: time for action.

Patients worldwide die every year from unrecognised oesophageal intubation, which is an avoidable complication of airway management usually resulting from human error. Unrecognised oesophageal intubation can occur in any patient of any age whenever intubation occurs regardless of the seniority or experience of the airway practitioner or others involved in the patient's airway management. The tragic fact is that it continues to happen despite improvements in monitoring, airway devices, and medical education. We review these improvements with strategies to eliminate this problem.

Formation of an Airway Lead Network: an essential patient safety initiative.

We outline the history, implementation and clinical impact of the formation of an Airway Lead Network. Although recommendations to improve patient safety in airway management are published and revised regularly, uniform implementation of such guidelines are applied sporadically throughout the hospital and prehospital settings. The primary roles of an Airway Lead are to ensure supply, quality and storage of airway equipment, promote the use of current practice guidelines as well as the organisation of training and audits. Locally, the Airway Lead may chair a multi-disciplinary airway committee within their organisation; an Airway Lead Network enables Airway Leads to share common problems and solutions to promote optimal airway management on a national level. Support from governing bodies is an essential part of this structure.

The impact of a digital joint school educational programme on post-operative outcomes following lower limb arthroplasty: a retrospective comparative cohort study.

BACKGROUND: As part of an ongoing service improvement project, a digital 'joint school' (DJS) was developed to provide education and support to patients undergoing total hip (THR) and total knee (TKR) replacement surgery. The DJS allowed patients to access personalised care plans and educational resources using web-enabled devices, from being listed for surgery until 12 months post-operation. The aim of this study was to compare a cohort of patients enrolled into the DJS with a cohort of patients from the same NHS trust who received a standard 'non-digital' package of education and support in terms of Health-Related Quality of Life (HRQoL), functional outcomes and hospital length of stay (LoS). METHODS: A retrospective comparative cohort study of all patients undergoing primary TKR/THR at a single NHS trust between 1st Jan 2018 and 31st Dec 2019 (n = 2406) was undertaken. The DJS was offered to all patients attending the clinics of early adopting surgeons and the remaining surgeons offered their patient's standard written and verbal information. This allowed comparison between patients that received the DJS (n = 595) and those that received standard care (n = 1811). For each patient, demographic data, LoS and patient reported outcome measures (EQ-5D-3L, Oxford hip/knee scores (OKS/OHS)) were obtained. Polynomial regressions, adjusting for age, sex, Charlson Comorbidity Index (CCI) and pre-operative OKS/OHS or EQ-5D, were used to compare the outcomes for patients receiving DJS and those receiving standard care. FINDINGS: Patients that used the DJS had greater improvements in their EQ-5D, and OKS/OHS compared to patients receiving standard care for both TKR and THR (EQ-5D difference: TKR coefficient estimate (est) = 0.070 (95%CI 0.004 to 0.135); THR est = 0.114 (95%CI 0.061 to 0.166)) and OKS/OHS difference: TKR est = 5.016 (95%CI 2.211 to 7.820); THR est = 4.106 (95%CI 2.257 to 5.955)). The DJS had a statistically significant reduction on LoS for patients who underwent THR but not TKR. CONCLUSION: The use of a DJS was associated with improved functional outcomes when compared to a standard 'non-digital' method. The improvements between pre-operative and post-operative outcomes in EQ-5D and OKS/OHS were higher for patients using the DJS. Furthermore, THR patients also had a shorter LoS.

Effects of Inertial Load on Sagittal Plane Kinematics of the Lower Extremity During Flywheel-Based Squats.

ABSTRACT: Worcester, KS, Baker, PA, and Bollinger, LM. Effects of inertial load on sagittal plane kinematics of the lower extremity during flywheel-based squats. J Strength Cond Res 36(1): 63-69, 2022-Increasing load increases flexion of lower extremity joints during weighted squats; however, the effects of inertial load on lower extremity kinematics during flywheel-based resistance training (FRT) squats remain unclear. The purpose of this study was to evaluate sagittal plane kinematics of lower extremity joints during FRT squats at various inertial loads. Nine recreationally resistance-trained subjects (3M, 6F) completed a bout of FRT squats with inertial loads of 0.050, 0.075, and 0.100 kg·m2. Two-dimensional sagittal plane kinematics were monitored with retroreflective markers at a rate of 60 Hz. Joint angles and angular velocities of the knee, trunk + hip, trunk inclination, and ankle were quantified throughout concentric and eccentric actions. Effects of inertial load were determined by repeated-measures analysis of variance with α = 0.05. Average power and average vertical velocity decreased with increasing inertial load, whereas average force increased. Minimal and maximal sagittal plane joint angles of the knee, trunk + hip, trunk inclination, and ankle were not significantly different among inertial loads. However, peak joint angular velocities of the knee and trunk + hip tended to decrease with increasing inertial load. Conversely trunk inclination and ankle dorsiflexion velocities were not significantly different among inertial loads. Increasing inertial load from 0.050 to 0.100 kg·m2 significantly reduces average power during FRT squats primarily by decreasing movement velocity, which seems to be specific to the knee and hip joints. It is possible that lower concentric energy input at high inertial loads prevents increased joint flexion during FRT squats.

Searching for Gravitational Waves from Cosmological Phase Transitions with the NANOGrav 12.5-Year Dataset.

We search for a first-order phase transition gravitational wave signal in 45 pulsars from the NANOGrav 12.5-year dataset. We find that the data can be modeled in terms of a strong first order phase transition taking place at temperatures below the electroweak scale. However, we do not observe any strong preference for a phase-transition interpretation of the signal over the standard astrophysical interpretation in terms of supermassive black hole mergers; but we expect to gain additional discriminating power with future datasets, improving the signal to noise ratio and extending the sensitivity window to lower frequencies. An interesting open question is how well gravitational wave observatories could separate such signals.

Emergency Airway Management in Patients with COVID-19: A Prospective International Multicenter Cohort Study.

BACKGROUND: Tracheal intubation for patients with COVID-19 is required for invasive mechanical ventilation. The authors sought to describe practice for emergency intubation, estimate success rates and complications, and determine variation in practice and outcomes between high-income and low- and middle-income countries. The authors hypothesized that successful emergency airway management in patients with COVID-19 is associated with geographical and procedural factors. METHODS: The authors performed a prospective observational cohort study between March 23, 2020, and October 24, 2020, which included 4,476 episodes of emergency tracheal intubation performed by 1,722 clinicians from 607 institutions across 32 countries in patients with suspected or confirmed COVID-19 requiring mechanical ventilation. The authors investigated associations between intubation and operator characteristics, and the primary outcome of first-attempt success. RESULTS: Successful first-attempt tracheal intubation was achieved in 4,017/4,476 (89.7%) episodes, while 23 of 4,476 (0.5%) episodes required four or more attempts. Ten emergency surgical airways were reported-an approximate incidence of 1 in 450 (10 of 4,476). Failed intubation (defined as emergency surgical airway, four or more attempts, or a supraglottic airway as the final device) occurred in approximately 1 of 120 episodes (36 of 4,476). Successful first attempt was more likely during rapid sequence induction versus non-rapid sequence induction (adjusted odds ratio, 1.89 [95% CI, 1.49 to 2.39]; P < 0.001), when operators used powered air-purifying respirators versus nonpowered respirators (adjusted odds ratio, 1.60 [95% CI, 1.16 to 2.20]; P = 0.006), and when performed by operators with more COVID-19 intubations recorded (adjusted odds ratio, 1.03 for each additional previous intubation [95% CI, 1.01 to 1.06]; P = 0.015). Intubations performed in low- or middle-income countries were less likely to be successful at first attempt than in high-income countries (adjusted odds ratio, 0.57 [95% CI, 0.41 to 0.79]; P = 0.001). CONCLUSIONS: The authors report rates of failed tracheal intubation and emergency surgical airway in patients with COVID-19 requiring emergency airway management, and identified factors associated with increased success. Risks of tracheal intubation failure and success should be considered when managing COVID-19.

Electrochemical quantification of d-glucose during the production of bioethanol from thermo-mechanically pre-treated wheat straw.

Mechanical pre-treatment (disc refining) of wheat straw, at both atmospheric and elevated pressure, is shown to be an efficient process to access fermentable monosaccharides, with the potential to integrate within the infrastructure of existing first-generation bioethanol plants. The mild, enzymatic degradation of this sustainable lignocellulosic biomass affords ca. 0.10-0.13 g/g (dry weight) of d-glucose quantifiable voltammetrically in real time, over a two hundred-fold range in experimental laboratory scales (25 mL to 5.0 L), with pressure disc refining of the wheat straw enabling almost twice the amount of d-glucose to be generated during the hydrolysis stage than experiments using atmospheric refining (0.06-0.09 g/g dry weight). Fermentation of the resulting hydrolysate affords 0.08-0.10 g/g (dry weight) of ethanol over similar scales, with ethanol productivity at ca. 37 mg/(L h). These results demonstrate that minimal cellulose decomposition occurs during pressure refining of wheat straw, in contrast to hemicellulose, and suggest that the development of green, mechanochemical processes for the scalable and cost-effective manufacture of second-generation bioethanol requires improved cellulose decomposition.

Difficult Airway Management in Adult Coronavirus Disease 2019 Patients: Statement by the Society of Airway Management.

The coronavirus disease 2019 (COVID-19) disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), often results in severe hypoxemia requiring airway management. Because SARS-CoV-2 virus is spread via respiratory droplets, bag-mask ventilation, intubation, and extubation may place health care workers (HCW) at risk. While existing recommendations address airway management in patients with COVID-19, no guidance exists specifically for difficult airway management. Some strategies normally recommended for difficult airway management may not be ideal in the setting of COVID-19 infection. To address this issue, the Society for Airway Management (SAM) created a task force to review existing literature and current practice guidelines for difficult airway management by the American Society of Anesthesiologists Task Force on Management of the Difficult Airway. The SAM task force created recommendations for the management of known or suspected difficult airway in the setting of known or suspected COVID-19 infection. The goal of the task force was to optimize successful airway management while minimizing exposure risk. Each member conducted a literature review on specific clinical practice section utilizing standard search engines (PubMed, Ovid, Google Scholar). Existing recommendations and evidence for difficult airway management in the COVID-19 context were developed. Each specific recommendation was discussed among task force members and modified until unanimously approved by all task force members. Elements of Appraisal of Guidelines Research and Evaluation (AGREE) Reporting Checklist for dissemination of clinical practice guidelines were utilized to develop this statement. Airway management in the COVID-19 patient increases HCW exposure risk. Difficult airway management often takes longer and may involve multiple procedures with aerosolization potential, and strict adherence to personal protective equipment (PPE) protocols is mandatory to reduce risk to providers. When a patient's airway risk assessment suggests that awake tracheal intubation is an appropriate choice of technique, and procedures that may cause increased aerosolization of secretions should be avoided. Optimal preoxygenation before induction with a tight seal facemask may be performed to reduce the risk of hypoxemia. Unless the patient is experiencing oxygen desaturation, positive pressure bag-mask ventilation after induction may be avoided to reduce aerosolization. For optimal intubating conditions, patients should be anesthetized with full muscle relaxation. Videolaryngoscopy is recommended as a first-line strategy for airway management. If emergent invasive airway access is indicated, then we recommend a surgical technique such as scalpel-bougie-tube, rather than an aerosolizing generating procedure, such as transtracheal jet ventilation. This statement represents recommendations by the SAM task force for the difficult airway management of adults with COVID-19 with the goal to optimize successful airway management while minimizing the risk of clinician exposure.