exRNA Atlas Analysis Reveals Distinct Extracellular RNA Cargo Types and Their Carriers Present across Human Biofluids.

To develop a map of cell-cell communication mediated by extracellular RNA (exRNA), the NIH Extracellular RNA Communication Consortium created the exRNA Atlas resource (https://exrna-atlas.org). The Atlas version 4P1 hosts 5,309 exRNA-seq and exRNA qPCR profiles from 19 studies and a suite of analysis and visualization tools. To analyze variation between profiles, we apply computational deconvolution. The analysis leads to a model with six exRNA cargo types (CT1, CT2, CT3A, CT3B, CT3C, CT4), each detectable in multiple biofluids (serum, plasma, CSF, saliva, urine). Five of the cargo types associate with known vesicular and non-vesicular (lipoprotein and ribonucleoprotein) exRNA carriers. To validate utility of this model, we re-analyze an exercise response study by deconvolution to identify physiologically relevant response pathways that were not detected previously. To enable wide application of this model, as part of the exRNA Atlas resource, we provide tools for deconvolution and analysis of user-provided case-control studies.

Single-stranded pre-methylated 5mC adapters uncover the methylation profile of plasma ultrashort Single-stranded cell-free DNA.

Whole-genome bisulfite sequencing (BS-Seq) measures cytosine methylation changes at single-base resolution and can be used to profile cell-free DNA (cfDNA). In plasma, ultrashort single-stranded cfDNA (uscfDNA, ∼50 nt) has been identified together with 167 bp double-stranded mononucleosomal cell-free DNA (mncfDNA). However, the methylation profile of uscfDNA has not been described. Conventional BS-Seq workflows may not be helpful because bisulfite conversion degrades larger DNA into smaller fragments, leading to erroneous categorization as uscfDNA. We describe the '5mCAdpBS-Seq' workflow in which pre-methylated 5mC (5-methylcytosine) single-stranded adapters are ligated to heat-denatured cfDNA before bisulfite conversion. This method retains only DNA fragments that are unaltered by bisulfite treatment, resulting in less biased uscfDNA methylation analysis. Using 5mCAdpBS-Seq, uscfDNA had lower levels of DNA methylation (∼15%) compared to mncfDNA and was enriched in promoters and CpG islands. Hypomethylated uscfDNA fragments were enriched in upstream transcription start sites (TSSs), and the intensity of enrichment was correlated with expressed genes of hemopoietic cells. Using tissue-of-origin deconvolution, we inferred that uscfDNA is derived primarily from eosinophils, neutrophils, and monocytes. As proof-of-principle, we show that characteristics of the methylation profile of uscfDNA can distinguish non-small cell lung carcinoma from non-cancer samples. The 5mCAdpBS-Seq workflow is recommended for any cfDNA methylation-based investigations.

Discovery and validation of plasma, saliva and multi-fluid plasma-saliva metabolomic scores predicting insulin resistance and diabetes progression or regression among Puerto Rican adults.

AIMS/HYPOTHESIS: Many studies have examined the relationship between plasma metabolites and type 2 diabetes progression, but few have explored saliva and multi-fluid metabolites. METHODS: We used LC/MS to measure plasma (n=1051) and saliva (n=635) metabolites among Puerto Rican adults from the San Juan Overweight Adults Longitudinal Study. We used elastic net regression to identify plasma, saliva and multi-fluid plasma-saliva metabolomic scores predicting baseline HOMA-IR in a training set (n=509) and validated these scores in a testing set (n=340). We used multivariable Cox proportional hazards models to estimate HRs for the association of baseline metabolomic scores predicting insulin resistance with incident type 2 diabetes (n=54) and prediabetes (characterised by impaired glucose tolerance, impaired fasting glucose and/or high HbA1c) (n=130) at 3 years, along with regression from prediabetes to normoglycaemia (n=122), adjusting for traditional diabetes-related risk factors. RESULTS: Plasma, saliva and multi-fluid plasma-saliva metabolomic scores predicting insulin resistance included highly weighted metabolites from fructose, tyrosine, lipid and amino acid metabolism. Each SD increase in the plasma (HR 1.99 [95% CI 1.18, 3.38]; p=0.01) and multi-fluid (1.80 [1.06, 3.07]; p=0.03) metabolomic scores was associated with higher risk of type 2 diabetes. The saliva metabolomic score was associated with incident prediabetes (1.48 [1.17, 1.86]; p=0.001). All three metabolomic scores were significantly associated with lower likelihood of regressing from prediabetes to normoglycaemia in models adjusting for adiposity (HRs 0.72 for plasma, 0.78 for saliva and 0.72 for multi-fluid), but associations were attenuated when adjusting for lipid and glycaemic measures. CONCLUSIONS/INTERPRETATION: The plasma metabolomic score predicting insulin resistance was more strongly associated with incident type 2 diabetes than the saliva metabolomic score. Only the saliva metabolomic score was associated with incident prediabetes.

Gender Differences With Ibutilide Effectiveness and Safety in Cardioversion of Atrial Fibrillation.

INTRODUCTION: Few studies have examined the use of ibutilide in noncardiac surgical populations. Our study considered the effectiveness and safety of ibutilide in cardioversion of atrial fibrillation (AF) in medical and surgical intensive care patients. METHODS: A retrospective chart review was performed for patients with a confirmed diagnosis of AF who were hemodynamically stable and received ibutilide after the initial diagnosis. Patients were administered 1 mg of ibutilide fumarate intravenous for 10 min with a second dose administered if AF persisted after 30 min. Patients were pretreated with intravenous magnesium sulfate if their blood magnesium level was <2 mg/dL. RESULTS: Fifty seven total female patients and 99 male patients received ibutilide. Females had an 88% conversion rate to normal sinus rhythm (NSR) compared to 68% in males (P = 0.008). A 70% successful return to NSR was observed in patients from all groups pretreated with magnesium sulfate (P = 0.045). One year after discharge, 74% of the patients stayed in the NSR. CONCLUSIONS: Within our population, pretreatment with magnesium sulfate followed by ibutilide was associated with increased conversion to NSR. Additionally, we noted that females had a higher conversion rate to NSR compared to males, regardless of whether they were pretreated with magnesium sulfate.

The Kinetics of COVID-19 Vaccine Response in a Community-Vaccinated Population.

We used a noninvasive electrochemical quantitative assay for IgG Abs to SARS-CoV-2 S1 Ag in saliva to investigate the kinetics of Ab response in a community-based population that had received either the Pfizer or Moderna mRNA-based vaccine. Samples were received from a total of 97 individuals, including a subset of 42 individuals who collected samples twice weekly for 3 mo or longer. In all, >840 samples were collected and analyzed. In all individuals, salivary SARS-CoV-2 S1 IgG Ab levels rose sharply in the 2-wk period after their second vaccination, with peak Ab levels seen at 10-20 d after vaccination. We observed that 20%, 10%, and 2.4% of individuals providing serial samples had a 90%, 95%, and 99% drop, respectively, from peak levels during the duration of monitoring, and in two patients, Abs fell to prevaccination levels (5%). The use of noninvasive quantitative salivary Ab measurement can allow widespread, cost-effective monitoring of vaccine response.

PIGMENT EPITHELIAL DETACHMENT THICKNESS AND VARIABILITY AFFECTS VISUAL OUTCOMES IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To evaluate the impact of pigment epithelial detachment (PED) thickness (i.e., height) and thickness variability on best-corrected visual acuity outcomes in patients with neovascular age-related macular degeneration in the Phase 3 HAWK and HARRIER trials. METHODS: Optical coherence tomography images from the pooled brolucizumab 6 mg and aflibercept 2 mg arms were analyzed for the maximum PED thickness across the macula at baseline through to week 96. Best-corrected visual acuity outcomes were compared in patients with different PED thickness and variability cut-off thresholds. RESULTS: Greater PED thickness at baseline or at week 12 was associated with lower mean best-corrected visual acuity gain from baseline to week 96 (baseline PED ≥200 µ m: +4.6 letters; <200 µ m: +7.0 letters; week 12 PED ≥100 µ m: +5.6 letters; <100 µ m: +6.6 letters). Eyes with the largest PED thickness variability from week 12 through week 96 gained fewer letters from baseline at week 96 (≥33 µ m: +3.3 letters; <9 µ m: +6.2 letters). Furthermore, increased PED thickness at week 48 was associated with higher prevalence of intraretinal and subretinal fluid. CONCLUSION: In this treatment-agnostic analysis, greater PED thickness and PED thickness variability were associated with poorer visual outcomes in patients with neovascular age-related macular degeneration and greater neovascular activity.

The Association Between Retinal Thickness Fluctuations and Visual Outcomes Under Anti-VEGF Therapy: A Systematic Review and Meta-Analysis.

INTRODUCTION: To examine the association between retinal thickness (RT) fluctuations and best-corrected visual acuity (BCVA) in eyes with neovascular AMD, macular edema secondary to RVO, and DME treated with anti-VEGF therapy. METHODS: A systematic search of Ovid MEDLINE, EMBASE, and the Cochrane Library was performed from January 2006 to March 2024. Studies comparing visual or anatomic outcomes of patients treated with anti-VEGF therapy, stratified by magnitudes of RT fluctuation, were included. ROBINS-I and Cochrane RoB 2 tools were used to assess risk of bias, and certainty of evidence was evaluated with GRADE criteria. Meta-analysis was performed with a random effects model. Primary outcomes were final BCVA and change in BCVA relative to baseline. RESULTS: 15725 articles were screened; 15 studies were identified in the systematic review and 5 studies were included in the meta-analysis. Final ETDRS VA was significantly worse in eyes with the highest level of RT fluctuation (weighted mean difference (WMD) = 7.86 letters; 95% CI, 4.97, 10.74; p < 0.00001; I² = 81%; 3136 eyes). RT at last observation was significantly greater in eyes with high RT fluctuations (WMD = -27.35 µm; 95% CI, -0.04, 54.75; p = 0.05; I2 = 88%; 962 eyes). CONCLUSIONS: Final visual outcome is associated with magnitude of RT fluctuation over the course of therapy. It is unclear whether minimizing RT fluctuations would help to optimize visual outcomes in patients treated with anti-VEGF therapy. These findings are limited by a small set of studies, risk of bias, and considerable heterogeneity.

Tracheal ulcer development from high volume, low-pressure cuffed endotracheal tubes.

INTRODUCTION: Iatrogenic injury to the larynx, particularly the vocal cords from prolonged intubation, has been well-studied; however, tracheal injuries are rarely reported. This study investigates the effectiveness of cuffed, high-volume, low-pressure endotracheal tubes in preventing the development of tracheal ulcers in intubated subjects. METHODS: A retrospective, IRB-approved review was performed on 1355 subjects who underwent percutaneous tracheostomy from 2002 to 2018. The presence and severity of tracheal ulcers were collected using documentation and photos during percutaneous tracheostomy placement. Primary outcome measures included: the length of time on a ventilator until tracheostomy (LOVT), length of hospitalization (LOH), and mortality in relationship to the severity of the tracheal injury. Data was reported as n (%) and median (IQR). The differences in means between groups were analyzed by ANOVA and Chi-square test with an alpha of 0.05. RESULTS: 206 subjects met the inclusion criteria; 65 subjects had an absence of tracheal injury, and 141 subjects developed tracheal ulcers. Subjects with tracheal ulcers were grouped by the following severity scale: no ulcer; mild ulcer (minimal mucosal erosion with exudate); moderate ulcer (mucosal erosion); and severe (tracheal ring exposure). There were no statistically significant differences in age (p = 0.99), gender (p = 0.83), BMI (p = 0.44), LOH (p = 0.88), LOVT (p = 0.93), and mortality (p = 0.306) between subjects with differing severity of ulcers. The average annual incidence of clinically significant ulcers (moderate and severe) was 2.2 %. CONCLUSIONS: The lack of statistical correlation between the duration of intubation and tracheal ulcer severity, along with a low annual incidence of tracheal ulcers, supports the improved safety of high-volume, low-pressure cylindrical, cuffed endotracheal tubes. This study is among the first to specifically focus on injuries at the level of the cuff and tip of endotracheal tubes with implications in preventive measures and potential product design changes.

Distinct Features of Plasma Ultrashort Single-Stranded Cell-Free DNA as Biomarkers for Lung Cancer Detection.

BACKGROUND: Using broad range cell-free DNA sequencing (BRcfDNA-Seq), a nontargeted next-generation sequencing (NGS) methodology, we previously identified a novel class of approximately 50 nt ultrashort single-stranded cell-free DNA (uscfDNA) in plasma that is distinctly different from 167 bp mononucleosomal cell-free DNA (mncfDNA). We hypothesize that uscfDNA possesses characteristics that are useful for disease detection. METHODS: Using BRcfDNA-Seq, we examined both cfDNA populations in the plasma of 18 noncancer controls and 14 patients with late-stage nonsmall cell lung carcinoma (NSCLC). In comparison to mncfDNA, we assessed whether functional element (FE) peaks, fragmentomics, end-motifs, and G-Quadruplex (G-Quad) signatures could be useful features of uscfDNA for NSCLC determination. RESULTS: In noncancer participants, compared to mncfDNA, uscfDNA fragments showed a 45.2-fold increased tendency to form FE peaks (enriched in promoter, intronic, and exonic regions), demonstrated a distinct end-motif-frequency profile, and presented with a 4.9-fold increase in G-Quad signatures. Within NSCLC participants, only the uscfDNA population had discoverable FE peak candidates. Additionally, uscfDNA showcased different end-motif-frequency candidates distinct from mncfDNA. Although both cfDNA populations showed increased fragmentation in NSCLC, the G-Quad signatures were more discriminatory in uscfDNA. Compilation of cfDNA features using principal component analysis revealed that the first 5 principal components of both cfDNA subtypes had a cumulative explained variance of >80%. CONCLUSIONS: These observations indicate that the distinct biological processes of uscfDNA and that FE peaks, fragmentomics, end-motifs, and G-Quad signatures are uscfDNA features with promising biomarker potential. These findings further justify its exploration as a distinct class of biomarker to augment pre-existing liquid biopsy approaches.

Biological biomarkers of oral cancer.

The oral squamous cell carcinoma (OSCC) 5 year survival rate of 41% has marginally improved in the last few years, with less than a 1% improvement per year from 2005 to 2017, with higher survival rates when detected at early stages. Based on histopathological grading of oral dysplasia, it is estimated that severe dysplasia has a malignant transformation rate of 7%-50%. Despite these numbers, oral dysplasia grading does not reliably predict its clinical behavior. Thus, more accurate markers predicting oral dysplasia progression to cancer would enable better targeting of these lesions for closer follow-up, especially in the early stages of the disease. In this context, molecular biomarkers derived from genetics, proteins, and metabolites play key roles in clinical oncology. These molecular signatures can help predict the likelihood of OSCC development and/or progression and have the potential to detect the disease at an early stage and, support treatment decision-making and predict treatment responsiveness. Also, identifying reliable biomarkers for OSCC detection that can be obtained non-invasively would enhance management of OSCC. This review will discuss biomarkers for OSCC that have emerged from different biological areas, including genomics, transcriptomics, proteomics, metabolomics, immunomics, and microbiomics.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY MORPHOLOGY AFTER RHEGMATOGENOUS RETINAL DETACHMENT REPAIR: ALIGN Post Hoc Analysis.

PURPOSE: To compare foveal avascular zone (FAZ) geometric indices using optical coherence tomography angiography (OCTA) in pneumatic retinopexy (PnR) versus pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD). FAZ morphology was assessed as a possible imaging feature of retinal displacement. METHODS: This ALIGN post hoc analysis included primary fovea-off RRDs that underwent successful PnR or PPV, and performed OCTA, and fundus autofluorescence at (FAF) 3 months postoperatively at St. Michael's Hospital, Toronto, Canada. FAZ area (mm 2 ), axial ratio, circularity, and roundness were measured, and FAF images were assessed for retinal displacement. RESULTS: Seventy-two patients were included, 78% (56/72) were male mean age was 60 ± 9 years, and 60% (43/72) were phakic. Sixty-five percent (47/72) and 35% (25/72) underwent PnR and PPV, respectively. The mean baseline logarithm of the minimum angle of resolution visual acuity was 1.49 ± 0.76. FAZ circularity was lower after PPV (0.629 ± 0.120) versus PnR (0.703 ± 0.122); P = 0.016. Sixty-six patients had gradable FAF images. Retinal displacement was present in 29% (19/66), 84.2% (16/19) of which had displacement in the macula. FAZ circularity was lower in eyes with displacement in the macula (0.613 ± 0.110) versus those without displacement (0.700 ± 0.124); P = 0.015. There was a moderate negative correlation between 12-month aniseikonia and FAZ circularity(r = -0.262; P = 0.041). CONCLUSION: FAZ circularity was lower after PPV and in eyes with retinal displacement in the macula. Circularity was negatively correlated with 12-month aniseikonia scores. FAZ circularity may be another imaging feature to consider postoperatively after RRD repair.

Anti-Vascular Endothelial Growth Factor Therapy Regimens for Polypoidal Choroidal Vasculopathy: A Systematic Review.

INTRODUCTION: There are no guidelines on the optimal anti-vascular endothelial growth factor (anti-VEGF) monotherapy regimen for patients with polypoidal choroidal vasculopathy (PCV). In this study, we aimed to assess the comparative safety and efficacy of different treatment regimens of anti-VEGF monotherapy for PCV. METHODS: We conducted a systematic literature search on Ovid MEDLINE, Embase, and Cochrane Library from January 2000 to May 2023 for comparative articles reporting on different treatment regimens of anti-VEGF agents in PCV. Our primary outcomes were the final best-corrected visual acuity (BCVA) and the change in BCVA from baseline. Secondary outcomes were the final retinal thickness (RT), the change in RT from baseline, the rate of polyp closure, and the incidence of adverse events. RESULTS: A total of 10,440 studies were screened, and seven studies reporting on 636 eyes with PCV at baseline were included in this systematic review. One RCT of 53 eyes found a similar final BCVA, change in BCVA from baseline, final RT, and complete polyp closure rate between a treat-and-extend (T&E) regimen and a bimonthly fixed-dosing regimen of aflibercept. This trial also found superiority of T&E for change in RT from baseline. One observational study of 33 eyes found a similar BCVA at last study observation between a pro re nata (PRN) regimen and bimonthly fixed-dosing regimen of aflibercept. One observational study of 42 eyes found a similar change in BCVA from baseline and complete polyp closure rate between a PRN regimen and bimonthly fixed-dosing regimen of aflibercept. One RCT of 249 eyes found a similar change in BCVA and RT from baseline, as well as polyp closure, between a T&E regimen and fixed 12-week dosing regimen of conbercept. One observational study of 30 eyes found a superiority of T&E aflibercept for change in BCVA and risk of polyp recurrence, compared to a PRN regimen. CONCLUSION: Overall, there is a paucity of evidence comparing various treatment regimens of anti-VEGF therapy in patients with PCV. This limited evidence suggests that current treatment regimens are similarly efficacious, though T&E aflibercept achieved superior outcomes when compared to bimonthly dosing or PRN in some individual studies. Further trials are needed to confirm or refute these findings.

Single-Droplet Microsensor for Ultra-Short Circulating EFGR Mutation Detection in Lung Cancer Based on Multiplex EFIRM Liquid Biopsy.

Liquid biopsy is a rapidly emerging field that involves the minimal/non-invasive assessment of signature somatic mutations through the analysis of circulating tumor DNA (ctDNA) shed by tumor cells in bodily fluids. Broadly speaking, the unmet need in liquid biopsy lung cancer detection is the lack of a multiplex platform that can detect a mutation panel of lung cancer genes using a minimum amount of sample, especially for ultra-short ctDNA (usctDNA). Here, we developed a non-PCR and non-NGS-based single-droplet-based multiplexing microsensor technology, "Electric-Field-Induced Released and Measurement (EFIRM) Liquid Biopsy" (m-eLB), for lung cancer-associated usctDNA. The m-eLB provides a multiplexable assessment of usctDNA within a single droplet of biofluid in only one well of micro-electrodes, as each electrode is coated with different probes for the ctDNA. This m-eLB prototype demonstrates accuracy for three tyrosine-kinase-inhibitor-related EGFR target sequences in synthetic nucleotides. The accuracy of the multiplexing assay has an area under the curve (AUC) of 0.98 for L858R, 0.94 for Ex19 deletion, and 0.93 for T790M. In combination, the 3 EGFR assay has an AUC of 0.97 for the multiplexing assay.

Urinary Cell-Free DNA in Liquid Biopsy and Cancer Management.

BACKGROUND: The current methodology used to detect, diagnose, and monitor many types of cancers requires invasive tissue biopsy testing. Recently, liquid biopsy using blood, plasma, urine, saliva, and various other bodily fluids has shown utility to solve many issues associated with tissue biopsy. Blood/plasma has received most of the attention within the liquid biopsy field, however, obtaining blood samples from patients is still somewhat invasive and requires trained professionals. Using urine to detect cell-free DNA cancer biomarkers offers a truly non-invasive sampling method that can be easily and reproducibly conducted by patients. CONTENT: Novel technologies and approaches have made the detection of small quantities of cell-free tumor DNA of varying lengths possible. Recent studies using urine circulating tumor DNA to detect cancer mutations and other biomarkers have shown sensitivity comparable to blood/plasma cell-free DNA liquid biopsy for many cancer types. Thus, urine cell-free DNA liquid biopsy may replace or provide supplementary information to tissue/blood biopsies. Further investigation with larger patient cohorts and standardization of pre-analytical factors is necessary to determine the utility of urine cell-free DNA liquid biopsy for cancer detection, diagnosis, and monitoring in a clinical setting. SUMMARY: In this mini-review we discuss the biological aspects of cell-free DNA in urine, numerous studies using urine cell-free DNA to detect urological cancers, and recent studies using urine cell-free DNA to detect and monitor non-urological cancers including lung, breast, colorectal, and other cancers.

Integrated Multiomics Analysis of Salivary Exosomes to Identify Biomarkers Associated with Changes in Mood States and Fatigue.

Fatigue and other deleterious mood alterations resulting from prolonged efforts such as a long work shift can lead to a decrease in vigilance and cognitive performance, increasing the likelihood of errors during the execution of attention-demanding activities such as piloting an aircraft or performing medical procedures. Thus, a method to rapidly and objectively assess the risk for such cognitive fatigue would be of value. The objective of the study was the identification in saliva-borne exosomes of molecular signals associated with changes in mood and fatigue that may increase the risk of reduced cognitive performance. Using integrated multiomics analysis of exosomes from the saliva of medical residents before and after a 12 h work shift, we observed changes in the abundances of several proteins and miRNAs that were associated with various mood states, and specifically fatigue, as determined by a Profile of Mood States questionnaire. The findings herein point to a promising protein biomarker, phosphoglycerate kinase 1 (PGK1), that was associated with fatigue and displayed changes in abundance in saliva, and we suggest a possible biological mechanism whereby the expression of the PGK1 gene is regulated by miR3185 in response to fatigue. Overall, these data suggest that multiomics analysis of salivary exosomes has merit for identifying novel biomarkers associated with changes in mood states and fatigue. The promising biomarker protein presents an opportunity for the development of a rapid saliva-based test for the assessment of these changes.

Airway Management in Surgical Patients With Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder, and the difficult airway is perhaps the anesthesiologists' quintessential concern. OSA and the difficult airway share certain similar anatomical, morphological, and physiological features. Individual studies and systematic reviews of retrospective, case-control, and large database studies have shown a likely association between patients with OSA and the difficult airway; OSA patients have a 3- to 4-fold higher risk of difficult intubation, difficult mask ventilation, or a combination of both. The presence of OSA should initiate proactive perioperative management in anticipation of a difficult airway. Prudent intraoperative management comprises the use of regional anesthesia where possible and considering an awake intubation technique where there is the presence of notable difficult airway predictors and risk of rapid desaturation following induction of general anesthesia. Familiarity with difficult airway algorithms, cautious extubation, and appropriate postoperative monitoring of patients with OSA are necessary to mitigate perioperative risks.

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.

Anti-VEGF intravitreal injections in the era of COVID-19: responding to different levels of epidemic pressure.

PURPOSE: Following the first wave of the COVID-19 pandemic in early 2020, the easing of strict measures to reduce its spread has led to a resurgence of cases in many countries at both the national and local level. This article addresses how guidance for ophthalmologists on managing patients with retinal disease receiving intravitreal injections of anti-vascular endothelial growth factor (VEGF) during the pandemic should be adapted to the local epidemic pressure, with more or less stringent measures implemented according to the ebb and flow of the pandemic. METHODS: The Vision Academy's membership of international retinal disease experts analyzed guidance for anti-VEGF intravitreal injections during the COVID-19 pandemic and graded the recommendations according to three levels of increasing epidemic pressure. The revised recommendations were discussed, refined, and voted on by the 14-member Vision Academy Steering Committee for consensus. RESULTS: Protocols to minimize the exposure of patients and healthcare staff to COVID-19, including use of personal protective equipment, physical distancing, and hygiene measures, should be routinely implemented and intensified according to local infection rates and pressure on the hospital/clinic or healthcare system. In areas with many COVID-19-positive clusters, additional measures including pre-screening of patients, postponement of non-urgent appointments, and simplification of complex intravitreal anti-VEGF regimens should be considered. Treatment prioritization for those at greatest risk of irreversible vision loss should be implemented in areas where COVID-19 cases are increasing exponentially and healthcare resources are strained. CONCLUSION: Consistency in monitoring of local infection rates and adjustment of clinical practice accordingly will be required as we move forward through the COVID-19 era. Ophthalmologists must continue to carefully weigh the risk-benefits to minimize the exposure of patients and healthcare staff to COVID-19, ensure that patients receive sight-saving treatment, and avoid the potential long-term impact of prolonged treatment postponement.

MANAGEMENT OF RETINAL PIGMENT EPITHELIUM TEAR DURING ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY.

PURPOSE: This article aims to review current evidence on the development, diagnosis, and management of retinal pigment epithelium (RPE) tear during anti-vascular endothelial growth factor (VEGF) therapy. METHODS: Literature searches were performed using MEDLINE/PubMed databases (cut-off date: August 2019). RESULTS: Three key recommendations were made based on existing literature and clinical experience: 1) Multimodal imaging with color fundus photography, optical coherence tomography, near-infrared reflectance imaging, fundus autofluorescence imaging, optical coherence tomography-angiography, and/or fluorescein angiography are recommended to diagnose RPE tear and assess risk factors. Retinal pigment epithelium tears can be graded by size and foveal involvement. 2) Patients at high risk of developing RPE tear should be monitored after each anti-VEGF injection. If risk factors worsen, it is not yet definitively known whether anti-VEGF administration should be more frequent, or alternatively stopped in such patients. Prospective research into high-risk characteristics is needed. 3) After RPE tear develops, anti-VEGF treatment should be continued in patients with active disease (as indicated by presence of intraretinal or subretinal fluid), although cessation of therapy should be considered in eyes with multilobular tears. CONCLUSION: Although evidence to support the assumption that anti-VEGF treatment contributes to development of RPE tear is not definitive, some data suggest this link.

Canadian Airway Focus Group updated consensus-based recommendations for management of the difficult airway: part 1. Difficult airway management encountered in an unconscious patient.

PURPOSE: Since the last Canadian Airway Focus Group (CAFG) guidelines were published in 2013, the literature on airway management has expanded substantially. The CAFG therefore re-convened to examine this literature and update practice recommendations. This first of two articles addresses difficulty encountered with airway management in an unconscious patient. SOURCE: Canadian Airway Focus Group members, including anesthesia, emergency medicine, and critical care physicians, were assigned topics to search. Searches were run in the Medline, EMBASE, Cochrane Central Register of Controlled Trials, and CINAHL databases. Results were presented to the group and discussed during video conferences every two weeks from April 2018 to July 2020. These CAFG recommendations are based on the best available published evidence. Where high-quality evidence was lacking, statements are based on group consensus. FINDINGS AND KEY RECOMMENDATIONS: Most studies comparing video laryngoscopy (VL) with direct laryngoscopy indicate a higher first attempt and overall success rate with VL, and lower complication rates. Thus, resources allowing, the CAFG now recommends use of VL with appropriately selected blade type to facilitate all tracheal intubations. If a first attempt at tracheal intubation or supraglottic airway (SGA) placement is unsuccessful, further attempts can be made as long as patient ventilation and oxygenation is maintained. Nevertheless, total attempts should be limited (to three or fewer) before declaring failure and pausing to consider "exit strategy" options. For failed intubation, exit strategy options in the still-oxygenated patient include awakening (if feasible), temporizing with an SGA, a single further attempt at tracheal intubation using a different technique, or front-of-neck airway access (FONA). Failure of tracheal intubation, face-mask ventilation, and SGA ventilation together with current or imminent hypoxemia defines a "cannot ventilate, cannot oxygenate" emergency. Neuromuscular blockade should be confirmed or established, and a single final attempt at face-mask ventilation, SGA placement, or tracheal intubation with hyper-angulated blade VL can be made, if it had not already been attempted. If ventilation remains impossible, emergency FONA should occur without delay using a scalpel-bougie-tube technique (in the adult patient). The CAFG recommends all institutions designate an individual as "airway lead" to help institute difficult airway protocols, ensure adequate training and equipment, and help with airway-related quality reviews.

RéSUMé: OBJECTIF: Depuis la dernière publication des lignes directrices du Canadian Airway Focus Group (CAFG) en 2013, la littérature sur la prise en charge des voies aériennes s'est considérablement étoffée. Le CAFG s'est donc réuni à nouveau pour examiner la littérature et mettre à jour ses recommandations de pratique. Ce premier article de deux traite de la prise en charge des voies aériennes difficiles chez un patient inconscient. SOURCES: Des sujets de recherche ont été assignés aux membres du Canadian Airway Focus Group, qui compte des médecins anesthésistes, urgentologues et intensivistes. Les recherches ont été menées dans les bases de données Medline, EMBASE, Cochrane Central Register of Controlled Trials et CINAHL. Les résultats ont été présentés au groupe et discutés lors de vidéoconférences toutes les deux semaines entre avril 2018 et juillet 2020. Les recommandations du CAFG sont fondées sur les meilleures données probantes publiées. Si les données probantes de haute qualité manquaient, les énoncés se fondent alors sur le consensus du groupe. CONSTATATIONS ET RECOMMANDATIONS CLéS: La plupart des études comparant la vidéolaryngoscopie à la laryngoscopie directe indiquent un taux de réussite plus élevé à la première tentative et globalement avec la vidéolaryngoscopie, ainsi que des taux de complication inférieurs. Ainsi, les ressources le permettant, le CAFG recommande dorénavant l'utilisation de vidéolaryngoscopes avec le type de lame convenablement sélectionné pour faciliter toutes les intubations trachéales. En cas d'échec de la première tentative d'intubation trachéale ou d'échec de positionnement du dispositif supraglottique (DSG), d'autres tentatives peuvent être entreprises tant que la ventilation et l'oxygénation du patient le permettent. Néanmoins, le nombre total de tentatives devrait être limité, à trois ou moins, avant de déclarer un échec et de considérer les options de « stratégie de retrait ¼. En cas d'échec de l'intubation, les options de stratégie de retrait chez un patient toujours oxygéné comprennent l'éveil (si possible), la temporisation avec un DSG, une dernière tentative d'intubation trachéale à l'aide d'une technique différente, ou une cricothyroïdotomie. L'échec de l'intubation trachéale, de la ventilation au masque facial et de la ventilation via un DSG accompagné d'une hypoxémie présente ou imminente, définit une urgence « impossible de ventiler, impossible d'oxygéner ¼. Le bloc neuromusculaire doit alors être confirmé ou mis en place, et une tentative finale de ventilation au masque, de positionnement du DSG ou d'intubation trachéale avec une lame de vidéolaryngoscopie hyper-angulée peut être réalisée, si cette approche n'a pas encore été essayée. Si la ventilation demeure impossible, une cricothyroïdotomie d'urgence devrait être réalisée sans délai utilisant une technique de scalpel-bougie-tube (chez le patient adulte). Le CAFG recommande à toutes les institutions de désigner une personne comme « leader des voies aériennes ¼ afin d'assister à la mise en place de protocoles pour les voies aériennes difficiles, d'assurer une formation et un équipement adéquats et d'aider aux examens de la qualité en rapport avec les voies aériennes.