A Novel Use of a Not So "EZ-Blocker" For Lung Isolation During a Direct Transaortic Transcatheter Aortic Valve Replacement.

Alternate access transcatheter aortic valve replacement presents unique challenges for anesthesiologists, including the possible need for lung isolation while working with space constraints around the patient's airway. Troubleshooting lung isolation in these cases can be challenging, requiring quick thinking and adaptability while maintaining patient safety. We present a case of direct transaortic transcatheter aortic valve replacement with an endobronchial blocker ("EZ-blocker") used for lung isolation that required a novel use of the "EZ-blocker" to achieve adequate lung isolation.

Effects of Short-Term Hand Tractor Operation on Upper Limb Responses of Users.

OBJECTIVES: Continuous exposure to hand-arm vibration integrated with poor posture and forceful movements are known causes of musculoskeletal disorders (MSD). In most related studies, force and vibration levels in experimental research is controlled. This study aims to determine how actual hand tractor field operation can affect the upper limb of users. It intends to characterize upper limb muscle activation applied during actual hand tractor usage. Lastly, it determines the immediate impacts on hand strength and perceived upper limb discomfort after the operation. METHODS: We recruited 15 farm operators with a mean working experience of 20.1 ± 12.2 years. They were asked to operate a hand tractor on paddy fields for at most 8 minutes. Handle vibration was measured using a tri-axial accelerometer. The total unweighted vibration acceleration was computed and used to represent the handle vibration magnitude. Muscle activation was measured using surface electromyography (sEMG). Six sEMG sensors were attached to the dominant and non-dominant side of the extensor carpi radialis (ECR), bicep, and deltoid. Pre- and post-task hand strength and subjective discomfort rating were also taken. RESULTS: The total unweighted handle vibration acceleration is 17.45 ± 7.53 m/s2. This exceeds the allowable safe value. Meanwhile, the percentage of maximum voluntary contraction (% MVC) of the muscles ranged from 6% to 14% with the ECR having a significantly higher activation (p < .05) than the bicep and deltoid. The post-task grip strength of the dominant hand was lower than its pre-task value (p < .01) while that of the non-dominant side did not vary significantly. There is a modest trend of higher hand discomfort of the non-dominant side on post-task than pre-task rating (p < .10). Although, overall, the perceived discomfort ranged from none to mild discomfort. CONCLUSION: In conclusion, the study showed an indication that the effects of vibration on humans are evident even at mild muscle exertion, with the exertion predominantly concentrated on the distal arm area clearly affecting grip strength and hand discomfort. In such cases, future recommendations can revolve around the improvement of the hand tractor handle grip to impose grip comfort and ease.

Caught by POCUS: Post-TAVR Pericardial Effusion.

Point-of-care ultrasound (POCUS) is becoming increasingly popular in the field of anesthesiology and is being incorporated into anesthesia resident education. Ultrasound provides a portable, quick, and inexpensive diagnostic tool to help guide clinicians in their decision making and management of medically complex patients. One important utilization of POCUS is helping to guide management of undifferentiated hypotension. We present a case of a patient who underwent a Transcatheter Aortic Valve Replacement (TAVR) procedure who then suffered from hypotension in the post-anesthesia care unit (PACU). POCUS was used to help identify the cause of the patient's hypotension and led to the diagnosis of a pericardial effusion.

Lessons learned from the COVID-19 pandemic for improved influenza control.

The World Health Organization noted that COVID-19 vaccination programmes could be leveraged to deliver influenza vaccination. In 2008, the International Federation of Pharmaceutical Manufacturers and Associations' (IFPMA) Influenza Vaccine Supply International Task Force (IVS) developed a survey method using the number of influenza vaccine doses distributed globally to estimate vaccination coverage rates. Seven hundred and ninety-seven million doses were distributed in 2021, representing a 205% increase over the 262 million doses distributed in 2004, exceeding the number of doses distributed during and after the 2009-2010 influenza pandemic. The most obvious explanation for the global increase is the enabling of critical elements of the vaccine ecosystem by decision-makers during the COVID-19 pandemic to reinforce implementation of influenza vaccination programs. Most of the improvements in performance of influenza programs during the COVID-19 pandemic can be classified in four categories: 1) promoting vaccination using tailored approaches for specific populations; 2) improving convenient access to influenza vaccines in COVID-safe settings; 3) improving reimbursement of seasonal influenza vaccination for priority groups; 4) maintaining the timing of vaccination to the autumn. In spite of the increase in rates of seasonal influenza vaccines distributed during the COVID-19 pandemic, globally, the rate of influenza dose distribution is sub-optimal, and a considerable proportion of the influenza infections remains preventable. To sustain the benefits from increased uptake of influenza vaccines, governments need to sustain the efforts made during the COVID-19 pandemic, and a number of global policy endeavours should be undertaken, including developing a clear global roadmap for achieving influenza control objectives, adopted by a WHA resolution, in line with the strategic objective 3 of the Global Influenza Strategy 2030, embedded in the Immunization Agenda 2030 (IA2030).

The non-classical major histocompatibility complex II protein SLA-DM is crucial for African swine fever virus replication.

African swine fever virus (ASFV) is a lethal animal pathogen that enters its host cells through endocytosis. So far, host factors specifically required for ASFV replication have been barely identified. In this study a genome-wide CRISPR/Cas9 knockout screen in porcine cells indicated that the genes RFXANK, RFXAP, SLA-DMA, SLA-DMB, and CIITA are important for productive ASFV infection. The proteins encoded by these genes belong to the major histocompatibility complex II (MHC II), or swine leucocyte antigen complex II (SLA II). RFXAP and CIITA are MHC II-specific transcription factors, whereas SLA-DMA/B are subunits of the non-classical MHC II molecule SLA-DM. Targeted knockout of either of these genes led to severe replication defects of different ASFV isolates, reflected by substantially reduced plating efficiency, cell-to-cell spread, progeny virus titers and viral DNA replication. Transgene-based reconstitution of SLA-DMA/B fully restored the replication capacity demonstrating that SLA-DM, which resides in late endosomes, plays a crucial role during early steps of ASFV infection.

Validity of the hydrogen ion mobilisation model during haemodialysis with time-dependent dialysate bicarbonate concentrations.

BACKGROUND: The hydrogen ion (H+) mobilisation model has been previously shown to accurately describe blood bicarbonate (HCO3) kinetics during haemodialysis (HD) when the dialysate bicarbonate concentration ([HCO3]) is constant throughout the treatment. This study evaluated the ability of the H+ mobilization model to describe blood HCO3 kinetics during HD treatments with a time-dependent dialysate [HCO3]. METHODS: Data from a recent clinical study where blood [HCO3] was measured at the beginning of and every hour during 4-h treatments in 20 chronic, thrice-weekly HD patients with a constant (Treatment A), decreasing (Treatment B) and increasing (Treatment C) dialysate [HCO3] were evaluated. The H+ mobilization model was used to determine the model parameter (Hm) that provided the best fit of the model to the clinical data using nonlinear regression. A total of 114 HD treatments provided individual estimates of Hm. RESULTS: Mean ± standard deviation estimates of Hm during Treatments A, B and C were 0.153 ± 0.069, 0.180 ± 0.109 and 0.205 ± 0.141 L/min (medians [interquartile ranges] were 0.145 [0.118,0.191], 0.159 [0.112,0.209], 0.169 [0.115,0.236] L/min), respectively; these estimates were not different from each other (p = 0.26). The sum of squared differences between the measured blood [HCO3] and that predicted by the model were not different during Treatments A, B and C (p = 0.50), suggesting a similar degree of model fit to the data. CONCLUSIONS: This study supports the validity of the H+ mobilization model to describe intradialysis blood HCO3 kinetics during HD with a constant Hm value when using a time-dependent dialysate [HCO3].

Diet-mediated gut microbial community modulation and signature metabolites as potential biomarkers for early diagnosis, prognosis, prevention and stage-specific treatment of colorectal cancer.

BACKGROUND: Over the last decade, studies have shown an increased incidence of colorectal cancer (CRC), particularly early onset colorectal cancer (EOCRC). Researchers have demonstrated that dietary behavior, especially among young adults, influences alterations in the gut microbial community, leading to an increased accumulation of pathogenic gut microbiota and a decrease in beneficial ones. Unfortunately, CRC is likely to be diagnosed at a late stage, increasing CRC-related mortality. However, this alteration in the gut microbiota (gut dysbiosis) can be harnessed as a biomarker for non-invasive diagnosis, prognosis, prevention, and treatment of CRC in an effort to prevent late diagnosis and poor prognosis associated with CRC. AIM OF REVIEW: This review discusses identification of potential biomarkers by targeting diet-mediated gut dysbiosis for the stage-specific diagnosis, prognosis, treatment, and prevention of CRC. Our findings provide a comprehensive insight into the potential of protumorigenic bacteria (e.g.pathogenic Escherichia coli,enterotoxigenic Bacteroides fragilis and Fusobacterium nucleatum) and their metabolites (e.g., colibactin and B. fragilis toxin) from gut dysbiosis as biomarkers for the diagnosis of CRC. KEY SCIENTIFIC CONCEPTS OF REVIEW: Collectively, a detailed understanding of the available data from current studies suggests that, further research on quantification of metabolites and stage-specific pathogenic microbial abundance is required for the diagnosis and treatment of CRC based on microbial dysbiosis. Specifically, future studies on faecal samples, from patient with CRC, should be conducted for F. nucleatum among different opportunistic bacteria, given its repeated occurrence in faecal samples and CRC biopsies in numerous studies. Finally, we discuss the potential of faecal microbial transplantation (FMT) as an intervention to restore damaged gut microbiota during CRC treatment and management.

Computer-aided design of proline-rich antimicrobial peptides based on the chemophysical properties of a peptide isolated from Olivancillaria hiatula.

The chemophysical properties of a peptide isolated from Olivancillaria hiatula were combined with computational tools to design new antimicrobial peptides (AMPs). The in silico peptide design utilized arbitrary sequence shuffling, AMP sequence prediction and alignments such that putative sequences mimicked those of proline-rich AMPs (PrAMPs) and were potentially active against bacteria. Molecular modelling and docking experiments were used to monitor peptide binding to some intracellular targets like bacteria ribosome, DnaK and LasR. Peptide candidates were tested in vitro for antibacterial and antivirulence activities. Chemophysical studies of peptide extract suggested hydrophobic, acidic and proline-rich peptide properties. The amino acid signature of the extract matched that of AMPs that inhibit intracellular targets. Two of the designed PrAMP peptides (OhPrP-3 and OhPrP-5) had high affinity for the ribosome and DnaK. OhPrP-1, 2 and 4 also had favorable interactions with the biomolecular targets investigated. Peptides had bactericidal activity at the minimum inhibitory concentration against Pseudomonas aeruginosa. The designed peptides docked strongly to LasR suggesting possible interference with quorum sensing, and this was corroborated by in vitro data where sub-inhibitory doses of all peptides reduced pyocyanin and pyoverdine expression. The designed peptides can be further studied for the development of new anti-infective agents.

Determining the impact of ex-vivo lung perfusion on hospital costs for lung transplantation: A retrospective cohort study.

INTRODUCTION: Ex-vivo lung perfusion (EVLP) has improved organ utilization for lung transplantation, but it is not yet known whether the benefits of this technology offset its additional costs. We compared the institutional costs of lung transplantation before vs after EVLP was available to identify predictors of costs and determine the health-economic impact of EVLP. METHODS: We performed a retrospective, before-after, propensity-score weighted cohort study of patients wait-listed for lung transplant at University Health Network (UHN) in Ontario, Canada, between January 2005 and December 2019 using institutional administrative data. We compared costs, in 2019 Canadian Dollars ($), between patients referred for transplant before EVLP was available (Pre-EVLP) to after (Modern EVLP). Cumulative costs were estimated using a novel application of multistate survival models. Predictors of costs were identified using weighted log-gamma generalized linear regression. RESULTS: A total of 1,199 patients met inclusion criteria (352 Pre-EVLP; 847 Modern EVLP). Mean total costs for the transplant hospitalization were $111,878 ($94,123-$130,767) in the Pre-EVLP era and $110,969 ($87,714-$136,000) in the Modern EVLP era. Cumulative five-year costs since referral were $278,777 ($82,575-$298,135) in the Pre-EVLP era and $293,680 ($252,832-$317,599) in the Modern EVLP era. We observed faster progression to transplantation when EVLP was available. EVLP availability was not a predictor of waitlist (cost ratio [CR] 1.04 [0.81-1.37]; p = 0.354) or transplant costs (CR 1.02 [0.80-1.29]; p = 0.425) but was associated with lower costs during posttransplant years 1&2 (CR 0.75 [0.58-1.06]; p = 0.05) and posttransplant years 3+ (CR 0.43 [0.26-0.74]; p = 0.001). CONCLUSIONS: At our center, EVLP availability was associated with faster progression to transplantation at no significant marginal cost.

Oxidative Stress and Apoptosis in Bisphenol AF-Induced Neurotoxicity in Zebrafish Embryos.

Bisphenol AF (BPAF) is a structural counterpart of bisphenol A that is utilized in the food and beverage industry. The present study investigated the potential mechanisms in BPAF-induced neurotoxicity in zebrafish embryos. The BPAF concentrations (0.03, 0.1, 0.3, and 1.0 µM) had no obvious effect on hatching, mortality, and body length of zebrafish larvae, while curved tail and pericardial edema were observed in the 1.0 µM group at 72 and 96 h postfertilization (hpf). Locomotor activity of the larvae (at 120 hpf) significantly decreased from dark to light but increased from light to dark transitions in BPAF groups (0.1, 0.3, and 1.0 µM). Acridine orange showed that BPAF significantly increased green fluorescence protein intensity (22.6%) in the 1.0 µM group. Consistently, the induced apoptosis significantly up-regulated caspase 3 at 0.3 µM (1.95-fold) and 1.0 µM (2.26-fold) and bax at 0.3 µM (1.60-fold) and 1.0 µM (1.78-fold), whereas bcl-2 expression was significantly decreased at 0.3 µM (0.72-fold) and 1.0 µM (0.53-fold). In addition, increased reactive oxygen species concentrations at 0.3 µM (27%) and 1.0 µM (61.4%) resulted in suppressed superoxide dismutase and catalase activities. Moreover, quantitative polymerase chain reaction results showed that BPAF (0.3 and 1.0 µM) significantly altered normal dopaminergic signaling where dat was up-regulated, while drd2a and th1 were down-regulated, in a concentration-dependent manner. Aberrations in dopamine-related genes were congruous with the dysregulations in neurodevelopment genes (sox11b, pax6a, syn2a, and rob2). Our findings suggest that BPAF-evoked oxidative stress and apoptosis could translate into phenotypical behavioral and neurodevelopmental abnormalities. These highlights could provide theoretical reference for risk assessment and act as an early indicator to BPAF exposure. Environ Toxicol Chem 2022;41:2273-2284. © 2022 SETAC.

An international observational study to assess the impact of the Omicron variant emergence on the clinical epidemiology of COVID-19 in hospitalised patients

BackgroundWhilst timely clinical characterisation of infections caused by novel SARS-CoV-2 variants is necessary for evidence-based policy response, individual-level data on infecting variants are typically only available for a minority of patients and settings. MethodsHere, we propose an innovative approach to study changes in COVID-19 hospital presentation and outcomes after the Omicron variant emergence using publicly available population-level data on variant relative frequency to infer SARS-CoV-2 variants likely responsible for clinical cases. We apply this method to data collected by a large international clinical consortium before and after the emergence of the Omicron variant in different countries. ResultsOur analysis, that includes more than 100,000 patients from 28 countries, suggests that in many settings patients hospitalised with Omicron variant infection less often presented with commonly reported symptoms compared to patients infected with pre-Omicron variants. Patients with COVID-19 admitted to hospital after Omicron variant emergence had lower mortality compared to patients admitted during the period when Omicron variant was responsible for only a minority of infections (odds ratio in a mixed-effects logistic regression adjusted for likely confounders, 0.67 [95% confidence interval 0.61 - 0.75]). Qualitatively similar findings were observed in sensitivity analyses with different assumptions on population-level Omicron variant relative frequencies, and in analyses using available individual-level data on infecting variant for a subset of the study population. ConclusionsAlthough clinical studies with matching viral genomic information should remain a priority, our approach combining publicly available data on variant frequency and a multi-country clinical characterisation dataset with more than 100,000 records allowed analysis of data from a wide range of settings and novel insights on real-world heterogeneity of COVID-19 presentation and clinical outcome.

Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses.

The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal outcomes with coronavirus disease 2019 (COVID-19) is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to an intensive care unit (ICU) with fatal COVID-19 outcomes, but not in individuals with nonfatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to an ICU with fatal and nonfatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an "original antigenic sin" type response.

Predicting endoscopic remission in Crohn's disease by the modified multiplier SES-CD (MM-SES-CD).

BACKGROUND AND AIMS: The Simple Endoscopic Score for Crohn's disease (SES-CD) is the primary tool for measurement of mucosal inflammation in clinical trials but lacks prognostic potential. We set to develop and validate a modified multiplier of the SES-CD (MM-SES-CD), which takes into consideration each individual parameter's prognostic value for achieving endoscopic remission (ER) while on active therapy. METHODS: In this posthoc analysis of three CD clinical trial programmes (n=350 patients, baseline SES-CD ≥ 3 with confirmed ulceration), data were pooled and randomly split into a 70% training and 30% testing cohort. The MM-SES-CD was designed using weights for individual parameters as determined by logistic regression modelling, with 1-year ER (SES-CD < 3) being the dependent variable. A cut point score for low and high probability of ER was determined by using the maximum Youden Index and validated in the testing cohort. RESULTS: Baseline ulcer size, extent of ulceration and presence of non-passable strictures had the strongest association with 1-year ER as compared with affected surface area, with differential weighting of individual parameters across disease segments being observed during logistic regression. The MM-SES-CD was generated using this weighted regression model and demonstrated strong discrimination for ER in the training dataset (area under the receiver operator curve (AUC) 0.83, 95% CI 0.78 to 0.94) and in the testing dataset (AUC 0.82, 95% CI 0.77 to 0.92). In comparison to the MM-SES-CD scoring model, the original SES-CD score lacks accuracy (AUC 0.60, 95% CI 0.55 to 0.65) for predicting the achievement of ER. CONCLUSIONS: We developed and internally validated the MM-SES-CD as an endoscopic severity assessment tool to predict one-year ER in patients with CD on active therapy.

SARS-CoV-2 environmental contamination from hospitalised patients with COVID-19 receiving aerosol-generating procedures.

BACKGROUND: Continuous positive airways pressure (CPAP) and high-flow nasal oxygen (HFNO) are considered 'aerosol-generating procedures' in the treatment of COVID-19. OBJECTIVE: To measure air and surface environmental contamination with SARS-CoV-2 virus when CPAP and HFNO are used, compared with supplemental oxygen, to investigate the potential risks of viral transmission to healthcare workers and patients. METHODS: 30 hospitalised patients with COVID-19 requiring supplemental oxygen, with a fraction of inspired oxygen ≥0.4 to maintain oxygen saturation ≥94%, were prospectively enrolled into an observational environmental sampling study. Participants received either supplemental oxygen, CPAP or HFNO (n=10 in each group). A nasopharyngeal swab, three air and three surface samples were collected from each participant and the clinical environment. Real-time quantitative polymerase chain reaction analyses were performed for viral and human RNA, and positive/suspected-positive samples were cultured for the presence of biologically viable virus. RESULTS: Overall 21/30 (70%) participants tested positive for SARS-CoV-2 RNA in the nasopharynx. In contrast, only 4/90 (4%) and 6/90 (7%) of all air and surface samples tested positive (positive for E and ORF1a) for viral RNA respectively, although there were an additional 10 suspected-positive samples in both air and surfaces samples (positive for E or ORF1a). CPAP/HFNO use or coughing was not associated with significantly more environmental contamination than supplemental oxygen use. Only one nasopharyngeal sample was culture positive. CONCLUSIONS: The use of CPAP and HFNO to treat moderate/severe COVID-19 did not appear to be associated with substantially higher levels of air or surface viral contamination in the immediate care environment, compared with the use of supplemental oxygen.

Utility of preoperative laboratory testing in ASA 1 & ASA 2 patients undergoing outpatient surgery in the United States.

STUDY OBJECTIVE: To assess the utility of preoperative testing in ASA physical status 1 and 2 patients undergoing outpatient surgery across several surgical specialties. DESIGN: Retrospective cohort study. PATIENTS: The American College of Surgeons National Surgical Quality Improvement Program database from 2017 to 2018 was queried to extract patients defined as ASA 1 and 2 who underwent outpatient surgeries. A total of 352,775 adult patients underwent outpatient surgery with 186,954 patients had at least one lab drawn within 30 days prior to the surgery. INTERVENTIONS: ASA physical status 1 and 2 patients who underwent outpatient surgeries. MEASUREMENTS: The primary independent variable was the utilization of preoperative laboratory testing. The primary outcomes were the occurrence of any medical or surgical complication adverse events within 30 days of discharge. In addition, we also examined hospital readmissions. A P value of 0.025 was used to avoid type I error for each primary outcome. MAIN RESULTS: In the overall cohort, 186,954 out of 352,775 (53%) of patients had at least one lab test. Hematology was the most common lab test ordered, 172,903 out of 352,755 patients (49%), followed by chemistry (43%), liver function (23%), and coagulation tests (11%). After adjusting for confounding factors, the use preoperative testing was not associated with overall medical complications, OR (95%CI) of 1.09 (1.00 to 1.18), P = 0.05 and overall surgical complications, 1.00 (0.92 to 1.08), P = 0.96 [Bonferroni corrected: medical complications OR (97.5% CI) of 1.09 (0.989 to 1.202), P = 0.0950 and overall surgical complications, 1.00 (0.918 to 1.093), P = 1.00. CONCLUSION: We detected a low utility of preoperative tests for ASA 1 and 2 patients undergoing a large variety of outpatient procedures. Our results support the elimination of preoperative laboratory test for ASA 1 and 2 undergoing ambulatory surgery.

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity.

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management.

Establishing quality indicators for pre-hospital advanced airway management: a modified nominal group technique consensus process.

BACKGROUND: Pre-hospital advanced airway management is a complex intervention composed of numerous steps, interactions, and variables that can be delivered to a high standard in the pre-hospital setting. Standard research methods have struggled to evaluate this complex intervention because of considerable heterogeneity in patients, providers, and techniques. In this study, we aimed to develop a set of quality indicators to evaluate pre-hospital advanced airway management. METHODS: We used a modified nominal group technique consensus process comprising three email rounds and a consensus meeting among a group of 16 international experts. The final set of quality indicators was assessed for usability according to the National Quality Forum Measure Evaluation Criteria. RESULTS: Seventy-seven possible quality indicators were identified through a narrative literature review with a further 49 proposed by panel experts. A final set of 17 final quality indicators composed of three structure-, nine process-, and five outcome-related indicators, was identified through the consensus process. The quality indicators cover all steps of pre-hospital advanced airway management from preoxygenation and use of rapid sequence induction to the ventilatory state of the patient at hospital delivery, prior intubation experience of provider, success rates and complications. CONCLUSIONS: We identified a set of quality indicators for pre-hospital advanced airway management that represent a practical tool to measure, report, analyse, and monitor quality and performance of this complex intervention.

Cost-effectiveness analysis of well-differentiated thyroid carcinoma surveillance using nuclear medicine procedures

Introduction@#Well-differentiated thyroid carcinoma (WDTC) is the most common type of thyroid cancer with a notable increasing incidence worldwide. It is prevalent among Filipino descent as compared to other nationalities. Its good prognosis and high survival rate predispose patients to lifetime surveillance with incomplete response, instead of death, as outcome measure. This eventually leads to increase in cost of care, utilization, and allocation of medical resources for the survivors of the disease. Thyroglobulin immunoradiometric assay (Tg IRMA) and I-131 diagnostic whole-body scan (dWBS) are two nuclear medicine procedures that are part of WDTC surveillance. Due to their varied availability in Asia-Pacific, most clinicians measure thyroglobulin (Tg) alone due to perceived cost-effectiveness. @*Objective@#This study aims to analyze the cost-effectiveness of two nuclear medicine procedures used in WDTC surveillance, namely thyroglobulin immunoradiometric assay and I-131 diagnostic whole-body scan, in detecting incomplete response. @*Methodology@#Three clinical guidelines on WDTC management were reviewed to identify frequency, total number and expenditure for surveillance, namely from the University of the Philippines-Philippine General Hospital in 2008 (PGH 2008), American Thyroid Association in 2015 (ATA 2015), and the Department of Health (DOH 2021). A Markov model was constructed to simulate a 36-month surveillance with complete and incomplete response to treatment as disease states. Parameter values like rate of incomplete response in WDTC patients, prognostic values per each surveillance test, and other relevant data were collected from literature search and established data. The cost of surveillance was based on the rates offered by Philippine General Hospital (PGH) Radioisotope Laboratory as of November 2022. One-way sensitivity was done to check robustness of results. @*Results@#ATA 2015 incurs the most expenses, amounting to PHP 14,600.00 to 20,450.00 ($ 254.19 – 356.04) for three years of surveillance, followed by DOH 2021 (PHP 11,700.00 – 15,600.00 or $ 203.74 – 271.65), and PGH 2008 (PHP 3,900.00 – 6,825.00 or $ 67.91 – 118.85). The thyroglobulin IRMA arm costs lower (PHP 17,784.00 or $ 309.74) than I-131 dWBS (PHP 271,875.00 or $ 4,735.13) in detecting incomplete response. I-131 dWBS should cost around PHP 570.00 (or $ 9.92) to be as cost-effective as the thyroglobulin IRMA.@*Conclusion@#This study has identified that thyroglobulin IRMA is more cost-effective than I-131 diagnostic whole-body scan in detecting incomplete response in WDTC patients. This supports the perceived cost-effectiveness of thyroglobulin measurement in surveillance, even without diagnostic whole body-scans. This study also identified that the new DOH 2021 guidelines will incur lesser expenditure in using nuclear medicine procedures for surveillance as compared to ATA 2015 guidelines. Local clinicians may also find it easier to follow as it is more suitable to the Philippine setting.

Subtractive CRISPR screen identifies the ATG16L1/vacuolar ATPase axis as required for non-canonical LC3 lipidation.

Although commonly associated with autophagosomes, LC3 can also be recruited to membranes by covalent lipidation in a variety of non-canonical contexts. These include responses to ionophores such as the M2 proton channel of influenza A virus. We report a subtractive CRISPR screen that identifies factors required for non-canonical LC3 lipidation. As well as the enzyme complexes directly responsible for LC3 lipidation in all contexts, we show the RALGAP complex is important for M2-induced, but not ionophore drug-induced, LC3 lipidation. In contrast, ATG4D is responsible for LC3 recycling in M2-induced and basal LC3 lipidation. Identification of a vacuolar ATPase subunit in the screen suggests a common mechanism for non-canonical LC3 recruitment. Influenza-induced and ionophore drug-induced LC3 lipidation lead to association of the vacuolar ATPase and ATG16L1 and can be antagonized by Salmonella SopF. LC3 recruitment to erroneously neutral compartments may therefore represent a response to damage caused by diverse invasive pathogens.