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Cytokinesis in plants is fundamentally different from that in animals and fungi. In plant cells, a cell plate forms through the fusion of cytokinetic vesicles and then develops into the new cell wall, partitioning the cytoplasm of the dividing cell. The formation of the cell plate entails multiple stages that involve highly orchestrated vesicle accumulation, fusion and membrane maturation, which occur concurrently with the timely deposition of polysaccharides such as callose, cellulose and cross-linking glycans. This review summarizes the major stages in cytokinesis, endomembrane components involved in cell plate assembly and its transition to a new cell wall. An animation that can be widely used for educational purposes further summarizes the process.

Background: Difficult facemask ventilation is perilous in children whose tracheas are difficult to intubate. We hypothesised that certain physical characteristics and anaesthetic factors are associated with difficult mask ventilation in paediatric patients who also had difficult tracheal intubation. Methods: We queried a multicentre registry for children who experienced “difficult” or “impossible” facemask ventilation. Patient and case factors known before mask ventilation attempt were included for consideration in this regularised multivariable regression analysis. Incidence of complications, and frequency and efficacy of rescue placement of a supraglottic airway device were also tabulated. Changes in quality of mask ventilation after injection of a neuromuscular blocking agent were assessed. Results: The incidence of difficult mask ventilation was 9% (483 of 5453 patients). Infants and patients having increased weight, being less than 5th percentile in weight for age, or having Treacher-Collins syndrome, glossoptosis, or limited mouth opening were more likely to have difficult mask ventilation. Anaesthetic induction using facemask and opioids was associated with decreased risk of difficult mask ventilation. The incidence of complications was significantly higher in patients with “difficult” mask ventilation than in patients without. Rescue placement of a supraglottic airway improved ventilation in 71% (96 of 135) of cases. Administration of neuromuscular blocking agents was more frequently associated with improvement or no change in quality of ventilation than with worsening. Conclusions: Certain abnormalities on physical examination should increase suspicion of possible difficult facemask ventilation. Rescue use of a supraglottic airway device in children with difficult or impossible mask ventilation should be strongly considered.

Purpose To help ensure that we were accurately and consistently evaluating applicants to our postgraduate year 1 (PGY1) pharmacy residency program, we performed a job analysis to inform a redesign of our selection process. Summary A diverse panel of subject matter experts from our program was convened to develop a task inventory; a list of knowledge, skills, abilities, and other characteristics necessary for success in our program; and behavioral snapshots representing especially strong or weak resident performance (ie, critical incidents). After achieving a priori thresholds of consensus, these items were used to augment our application screening instrument (eg, development of anchored rating scales), build an online supplemental application consisting of a personality test and situational judgment test, develop a work sample consisting of a patient case presentation, and enhance the structure of our interviews (eg, by asking a consistent pattern of questions for all candidates). Preceptors reported that the redesigned process was more organized, easier to complete, and facilitated greater rating consistency. Conclusion Job analysis represents an approach to designing selection processes that are more valid, reliable, transparent, and fair. Based on our experiences, recommendations for those who are considering changes to their selection process are provided.

Surgical treatment of craniosynostosis with cranial vault reconstruction in infants is associated with significant blood loss. The optimal blood management approach is an area of active investigation. Thromboelastography (TEG) was used to examine changes in coagulation after surgical blood loss that was managed by transfusion with either whole blood or blood components. Transfusion type was determined by availability of whole blood from the blood bank.This retrospective study examined differences in posttransfusion TEG maximum amplitude (MA), a measure of the maximum clot strength, for patients transfused with whole blood or blood components. We included all patients less than 24 months old who underwent cranial vault remodeling, received intraoperative transfusions with whole blood or blood components, and had baseline and posttransfusion TEG measured. Whole blood was requested for all patients and was preferentially used when it was available from the American Red Cross.Of 48 eligible patients, 30 received whole blood and 18 received blood components. All patients received an intraoperative antifibrinolytic agent. The posttransfusion MA in the whole blood group was 61.8 mm (IQR 59.1, 64.1) compared to 57.9 mm (IQR 50.5, 60.9) in the blood components group (P = 0.010). There was a greater posttransfusion decrease in MA for patients transfused with blood components (median decrease of 7.7 mm [IQR -3.4, 6.3]) compared with whole blood (median decrease of 2.1 mm [IQR -9.6, 7.5] P 0.001).Transfusion with blood components was associated with a greater decrease in MA that was likely related to decreased postoperative fibrinogen in this group. Patients who received whole blood had higher postoperative fibrinogen levels.

Introduction: Pretransplant cardiovascular risk may be amplified after renal transplant, but little is known about its impact on graft outcomes. Research question: The purpose of this study was to determine if pretransplant cardiovascular risk was associated with graft outcomes. Design: This retrospective study included deceased-donor renal transplant recipients from 2010-2015. Atherosclerotic cardiovascular disease risk for patients without prior disease was calculated and patients were categorized into high (score >20%), intermediate (7.5-20%), and low risk (Results: In patients without prior atherosclerotic cardiovascular disease (N = 115), graft failure rates (4.5% vs 11.3% vs 12.5%; ( P = 0.64) and major adverse cardiovascular events (9.1% vs 13.2% vs 5.0%; P = 0.52) were similar in the high, intermediate, and low risk groups. In those with prior disease (N = 220), rates of primary nonfunction (6.8% vs 1.7%; P = 0.04), major adverse cardiovascular events (7.3% vs 2.6%; P = 0.01), and heart failure (10.9% vs 3.5%; P = 0.02) were higher than those without cardiovascular; rates of major adverse cardiovascular events and heart failure were insignificant after adjusting for age, gender, and race. Other outcomes were not different. Outcomes did not differ based on pretransplant cardiovascular risk. Discussion: Pretransplant atherosclerotic cardiovascular disease was associated with increased early graft failure but similar outcomes at 3-years, suggesting cardiac risk alone should not exclude transplantation.

Purpose of review Children are at risk of severe hypoxemia in the perioperative period owing to their unique anatomy and physiology. Safe and effective airway management strategies are therefore key to the practice of pediatric anesthesia. The goal of this review is to highlight recent publications (2019-2021) aimed to advance pediatric airway safety and to highlight a proposed simple, pediatric-specific, universal framework to guide clinical practice. Recent findings Recent investigations demonstrate that infants with normal and difficult airways experience high incidences of multiple laryngoscopy attempts and resulting hypoxemia. Video laryngoscopy may improve tracheal intubation first attempt success rate in infants with normal airways. In infants with difficult airways, standard blade video laryngoscopy is associated with higher first attempt success rates over non-standard blade video laryngoscopy. Recent studies in children with Pierre Robin sequence and mucopolysaccharidoses help guide airway equipment and technique selection. Department airway leads and hospital difficult airway services are necessary to disseminate knowledge, lead quality improvement initiatives, and promote evidence-based practice guidelines. Summary Pediatric airway management morbidity is a common problem in pediatric anesthesia. Improvements in individual practitioner preparation and management strategies as well as systems-based policies are required. A simple, pediatric-specific, universal airway management framework can be adopted for safe pediatric anesthesia practice.

To use large-scale electronic health record (EHR) data to develop machine learning models predicting malignant transformation of oral lesions.A multi-institutional health system database was used to identify a retrospective cohort of patients with biopsied oral lesions. The primary outcome was malignant transformation. Chart review and automated system database queries were used to identify a range of demographic, clinical, and pathologic variables. Machine learning was used to develop predictive models for progression to malignancy.There were 2192 patients with a biopsied oral lesion, of whom 1232 had biopsy proven oral dysplasia. There was malignant transformation in 34% of patients in the oral lesions dataset, and in 54% of patients in the dysplasia subset. Multiple machine learning-based models were trained on the data in two experiments, (a) including all patients with biopsied oral lesions and (b) including only patients with biopsy-proven dysplasia. In the first experiment, the best machine learning models predicted malignant transformation among the biopsied oral lesions with an area under the curve (AUC) of 86%. In the second experiment, the random forest model predicted malignant transformation among lesions with dysplasia with an AUC of 0.75. The most influential features were dysplasia grade and the presence of multiple lesions, with smaller influences from other features including anemia, histopathologic description of atypia, and other prior cancer history.With diverse features from EHR data, machine learning approaches are feasible and allow for generation of models that predict which oral lesions are likely to progress to malignancy.3 Laryngoscope, 2022.

Alison Dillman,1 Michael J Zoratti,2 Jay JH Park,3 Grace Hsu,2 Louis Dron,2 Gerald Smith,2 Ofir Harari,2 Craig R Rayner,4 Noor-E Zannat,2 Alind Gupta,2 Eric Mackay,5 Paul Arora,6 Zelyn Lee,7 Edward J Mills2 1School of Public Health, Faculty of Medicine, Imperial College London, London, England; 2Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada; 3Department of Experimental Medicine, University of British Columbia, Vancouver, British Columbia, Canada; 4Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia; 5Department of Statistical Sciences, University of Toronto, Toronto, Canada; 6Dalla Lana School of Public Health, University of Toronto, Toronto, Canada; 7Department of Physiology & Department of Neuroscience, University of Toronto, Toronto, CanadaCorrespondence: Jay JH Park Tel +1 604 294-3823Email jayhpark1@alumni.ubc.caPurpose: A multitude of randomized controlled trials (RCTs) have emerged in response to the novel coronavirus disease (COVID-19) pandemic. Understanding the distribution of trials among various settings is important to guide future research priorities and efforts. The purpose of this review was to describe the emerging evidence base of COVID-19 RCTs by stages of disease progression, from pre-exposure to hospitalization.Methods: We collated trial data across international registries: ClinicalTrials.gov; International Standard Randomised Controlled Trial Number Registry; Chinese Clinical Trial Registry; Clinical Research Information Service; EU Clinical Trials Register; Iranian Registry of Clinical Trials; Japan Primary Registries Network; German Clinical Trials Register (up to 7 October 2020). Active COVID-19 RCTs in international registries were eligible for inclusion. We extracted trial status, intervention(s), control, sample size, and clinical context to generate descriptive frequencies, network diagram illustrations, and statistical analyses including odds ratios and the Mann–Whitney U-test.Results: Our search identified 11503 clinical trials registered for COVID-19 and identified 2388 RCTs. After excluding 45 suspended RCTs and 480 trials with unclear or unreported disease stages, 1863 active RCTs were included and categorized into four broad disease stages: pre-exposure (n=107); post-exposure (n=208); outpatient treatment (n=266); hospitalization, including the intensive care unit (n=1376). Across all disease stages, most trials had two arms (n=1500/1863, 80.52%), most often included (hydroxy)chloroquine (n=271/1863, 14.55%) and were US-based (n=408/1863, 21.90%). US-based trials had lower odds of including (hydroxy)chloroquine than trials in other countries (OR: 0.63, 95% CI: 0.45– 0.90) and similar odds of having two arms compared to other geographic regions (OR: 1.05, 95% CI: 0.80– 1.38).Conclusion: There is a marked difference in the number of trials across settings, with limited studies on non-hospitalized persons. Focus on pre- and post-exposure, and outpatients, is worthwhile as a means of reducing infections and lessening the health, social, and economic burden of COVID-19.Keywords: COVID-19, novel coronavirus 2019, systematic review, randomized controlled trials

Children have unique characteristics that make them particularly vulnerable to perioperative adverse events. Skilled airway management is a cornerstone of high-quality anesthetic management. The use of hybrid airway techniques is a critical tool for the pediatric anesthesiologist. Point-of-care ultrasonography has an expanding role in airway management, from preoperative assessment of airway pathology and gastric contents to confirmation of tracheal intubation and identification of the cricothyroid membrane. The exciting fields of 3-dimensional printing, artificial intelligence, and machine learning are areas of innovation that will transform pediatric difficult airway management in years to come.

Background The AABB (American Association of Blood Banks) and the College of American Pathologists (CAP) regulations call on blood banks to address the risk of misidentification of a patient's blood type, which can result in transfusion of a mismatched product. Transfusion of mismatched blood product is potentially fatal due to acute hemolytic transfusion reaction and is considered a preventable event. CAP regulations outline options to reduce risk of mistransfusion by either documenting the ABO group of the intended recipient on a second sample collected at a separate phlebotomy, or utilizing a mechanical barrier system or electronic identification verification system that ensures the patient from whom the pretransfusion specimen was collected is the same patient who is about to be transfused. Study design and methods An electronic or barrier system was not available for implementation at our institution, therefore we developed a protocol for a two-sample verification system. The first determination is performed on a current sample and the second by one of the following methods: (a) comparison with previous laboratory records, (b) testing a second sample collected at a time different from the first sample (i.e., laboratory specimen available with a different timestamp, or a new blood sample). Results We improved our transfusion process and implemented a policy to require a second sample to confirm a patient's blood type. We also implemented workflows to obtain blood type confirmation from history of a second blood type result from previous laboratory records, including a policy to accept previous blood type records from an outside laboratory. Conclusions We describe a practice change for two-sample verification for type and screen in a large-scale pediatric hospital. We outline specific workflows for pre-operative and emergency transfusion scenarios, and pediatric-specific challenges.

The severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]) pandemic has challenged medical systems and clinicians globally to unforeseen levels. Rapid spread of COVID-19 has forced clinicians to care for patients with a highly contagious disease without evidence-based guidelines. Using a virtual modified nominal group technique, the Pediatric Difficult Intubation Collaborative (PeDI-C), which currently includes 35 hospitals from 6 countries, generated consensus guidelines on airway management in pediatric anesthesia based on expert opinion and early data about the disease. PeDI-C identified overarching goals during care, including minimizing aerosolized respiratory secretions, minimizing the number of clinicians in contact with a patient, and recognizing that undiagnosed asymptomatic patients may shed the virus and infect health care workers. Recommendations include administering anxiolytic medications, intravenous anesthetic inductions, tracheal intubation using video laryngoscopes and cuffed tracheal tubes, use of in-line suction catheters, and modifying workflow to recover patients from anesthesia in the operating room. Importantly, PeDI-C recommends that anesthesiologists consider using appropriate personal protective equipment when performing aerosol-generating medical procedures in asymptomatic children, in addition to known or suspected children with COVID-19. Airway procedures should be done in negative pressure rooms when available. Adequate time should be allowed for operating room cleaning and air filtration between surgical cases. Research using rigorous study designs is urgently needed to inform safe practices during the COVID-19 pandemic. Until further information is available, PeDI-C advises that clinicians consider these guidelines to enhance the safety of health care workers during airway management when performing aerosol-generating medical procedures. These guidelines have been endorsed by the Society for Pediatric Anesthesia and the Canadian Pediatric Anesthesia Society.

Background: Maximal dosing of early antimicrobials with high loading and maintenance doses may optimize pharmacokinetic parameters to achieve and maintain therapeutic concentrations at the site of infection in septic shock. Little is known about the current practice of early antimicrobial dosing in septic shock. Objective: To characterize early antimicrobial dosing in patients in the resuscitation phase of septic shock. Methods: This retrospective cohort study included patients admitted to the medical intensive care unit (ICU) with septic shock. The primary outcome was the percentage of early antibiotic orders that were maximal or conservative during the resuscitation (0 to 48 hours) phase based on predefined dosing criteria. The secondary outcomes were the correlations of different dosing strategies on hospital length of stay (LOS), ICU LOS, and hospital mortality. Results: This study evaluated 161 patients and 692 antibiotic orders; 504 (72.8%) of the orders during the resuscitation phase were conservative. There were no differences in mortality (odds ratio = 0.66; 95% confidence interval = 0.35-1.25; P = .20), hospital LOS (median = 20 [interquartile range (IQR) = 10-34] vs 19 [IQR = 11-32] days; P = .93), or ICU LOS (median = 8 [IQR = 5-16] vs 9 [IQR = 5-15] days; P = .63) between maximal and conservative dosing groups, respectively, in the resuscitation phase. Limitations of this study included the use of institution-specific antimicrobial dosing guidelines and its retrospective nature. Conclusions: Early antibiotic dosing is conservative for a majority of patients in septic shock. Future studies are needed to evaluate the impact of dosing strategy on patient-centered outcomes in septic shock.

Tweetable abstract Recent RWD studies suggest that the performance of immunotherapy in NSCLC is not as good as that seen in RCTs. However, analyses using RWD (and their interpretation) require careful appraisal and quantification of possible sources of bias.

ImportanceThe external validity of survival outcomes derived from clinical practice data from US patients with advanced non–small cell lung cancer (NSCLC) is not known and is of potential importance because it may be used to support regulatory decision-making and health technology assessment outside of the US.ObjectiveTo evaluate whether overall survival (OS) estimates for a selected group of patients with advanced NSCLC from a large US clinical practice database are transportable to Canadian patients receiving the same systemic therapies.Design, Setting, and ParticipantsThis retrospective multicenter cohort study used transportability analysis to assess whether adjustment for pretreatment characteristics of eligible patient cohorts could reliably approximate OS estimated from US-based samples to Canadian populations. A total of 17 432 eligible adult patients who were diagnosed de novo with advanced NSCLC on or after January 1, 2011, were included in the analysis and followed up until September 30, 2020. Because data on race and ethnicity were available in the US database but not the Canadian database and because racial and ethnic distribution was likely to be similar between US and Canadian patients, these characteristics were not analyzed.ExposuresInitiation of platinum-doublet chemotherapy or pembrolizumab monotherapy as first-line systemic treatment for advanced NSCLC.Main Outcomes and MeasuresOS measured from the time of initiation of the respective treatment regimen.ResultsAmong 17 432 eligible patients, 15 669 patients from the US and 1763 patients from Canada were included in the analysis. Of those, 11 863 patients (sample size–weighted estimates of mean [SD] age, 68.0 [9.3] years; 6606 [55.7%] male; 10 100 from the US and 1763 from Canada) were included in the subset of patients with complete data for baseline covariates. A total of 13 532 US patients received first-line chemotherapy, and 2137 received first-line pembrolizumab monotherapy. Of those, 8447 patients (62.4%) in the first-line chemotherapy group and 1653 patients (77.3%) in the first-line pembrolizumab group had complete data on baseline covariates for outcome model estimation. A total of 1476 Canadian patients who received first-line chemotherapy and 287 patients who received first-line pembrolizumab monotherapy were identified from the target population. After standardization to baseline patient covariates in the Canadian cohorts, transported OS estimates revealed a less than 5% mean absolute difference from the observed OS in the target population (0.56% over 60 months of follow-up in the first-line chemotherapy group and 4.54% over 30 months of follow-up in the first-line pembrolizumab group). Negative control analysis using a mismatched outcome model revealed a 6.64% discrepancy and an incompatible survival curve shape. The results were robust to assumptions of random missingness for baseline covariates, to unadjusted differences in baseline metastases and comorbidities, and to differences in the standard of care between the US and Canada related to administration of second-line anti–programmed cell death 1 ligand 1 immunotherapy for patients who initiated first-line chemotherapy.Conclusions and RelevanceThe results of this cohort study suggest that, under specific circumstances, OS estimates from US clinical practice data can be adjusted using baseline clinical characteristics to closely approximate OS in selected groups of Canadian patients with advanced NSCLC. These results may have implications for regulatory decision-making and health technology assessment in target populations outside of the US.

Background: The design of a videolaryngoscope blade may affect its efficacy. We classified videolaryngoscope blades as standard and non-standard shapes to compare their efficacy performing tracheal intubation in children enrolled in the Paediatric Difficult Intubation Registry. Methods: Cases entered in the Registry from March 2017 to January 2020 were analysed. We compared the success rates of initial and eventual tracheal intubation, complications, and technical difficulties between the two groups and by weight stratification. Results: Videolaryngoscopy was used in 1313 patients. Standard and non-standard blades were used in 529 and 740 patients, respectively. Both types were used in 44 patients. In children weighing

IntroductionSocial determinants of health (SDOH) has a significant impact on access to health. Risk stratification of patients who have difficulty accessing care could allow for triaging of peri-operative resources. Unfortunately, there is a limited amount of SES factors available to study in electronic health records (EHR). Objectives and ApproachOur objective was to understand the SES and location risk factors that are associated with paediatric patients arriving late to the hospital for elective surgery. We conducted a retrospective study of paediatric patients requiring elective surgery from 2015-2019. Spatial linkage of EHR data with US Census–ACS 2017 data was conducted. Analysis was at patient and neighbourhood block group levels. Statistical analysis was conducted utilizing SAS, Python and ArcGIS. ResultsOur study had 40,943 patients with 7,453 patients (18.2%) who arrived ≥15 minutes late from their scheduled arrival. Patient level risk factors for arriving late included younger age, Black and Indian patients, non-English speaking, government insurance, increased co-morbidities and earlier appointments. The median time of arrival for patients arriving late was 23.0 minutes (18.0-33.0 minutes IQR), versus the on-time group of 7 min (4-22 minutes IQR) early. Median drive time and distance, using network analysis was not a significant factor. Statistically significant neighbourhood risk factors for arriving late included block groups with high unemployment, households receiving public assistance, low income households, higher number of high-school drop outs, female-headed households, more renter-occupied houses, and areas with high turnover. Logistic regression demonstrated neighbourhoods with the lowest quintile SES were 30% more likely to be late than the areas with the highest SES (p

The aim of this study was to identify the features and independent risk factors associated with recurrence and mortality in patients with brain abscesses of head and neck origin.We designed a retrospective study of patients diagnosed with a brain abscess at the Massachusetts General Hospital between 1980 and 2017. Inclusion criteria were complete medical records, including medical and surgical history; and radiographic and microbiologic data. Multinomial logistic regression and Gray's test were used to evaluate the independent variables associated with recurrence and mortality.Eighty-eight cases met the inclusion criteria. Of these, 48 patients (54.5%) were men (mean age 50.5 ± 18.8 years). Significant association between etiology and cultured organisms was found only in cases of neurosurgical intervention with staphylococcal or streptococcal isolates (P.05). Seizure activity was the only significant predictor of recurrence. Predictors of mortality included advanced age (P = .005); staphylococcal infection (P = .029); low monocyte count (P = .004); hyponatremia (P = .002); elevated blood urea nitrogen (P = .000); elevated creatinine (P = .002); hyperglycemia (P = .023); and status at discharge (P = .000).Independent risk factors, such as low monocyte count, hyponatremia, renal dysfunction, and hyperglycemia, were found to be associated with higher mortality rates in patients with brain abscesses of head and neck origin. These abnormalities should be promptly recognized and aggressively treated.

Background: Enrollment of participants to control arms in clinical trials can be challenging. This is particularly an issue in oncology trials where the standard-of-care is shifting rapidly and several promising experimental treatments are undergoing phase III testing. Novel methods for utilizing external control data may mitigate these challenges, but applied examples are sparse. Here, we therefore illustrate how Bayesian dynamic borrowing of external individual patient level control data from similar clinical trials can often reduce randomization to the control intervention without substantially trading-off precision. We further explore which types of scenarios yield viable trade-offs, and which do not. Patients and methods: We obtained individual patient data on patients being treated with second-line therapy for non-small cell lung cancer from Project Data Sphere with minimal in/exclusion criteria restrictions, and applied Bayesian hierarchical models with uninformative priors to generate illustrative synthetic control groups. Results: Four phase III clinical trials were identified and utilized in our analysis. Even when studies which are knowingly incongruent with one another are selected to generate a synthetic control, the nature of this methodology minimizes improper borrowing from historical data. The use of a small concurrent control group within a trial greatly reduces penalized selection, and our results demonstrate the ability to reduce allocation to the control group by up to 80% with a minimal increase in uncertainty when closely matched historical data is available. Conclusion: Dynamic borrowing using Bayesian hierarchical models with uninformative priors represents a novel approach to utilizing external controls for comparative estimates using single arm evidence. Keywords: Synthetic control, NSCLC, Oncology, Bayesian hierarchical model, Dynamic borrowing, External control

Objective The aim of this study was to answer the following clinical question: “In patients admitted to a tertiary care hospital with a diagnosis of brain abscess, how common is odontogenic etiology?” Study Design We designed a retrospective study of patients with brain abscesses diagnosed at the Massachusetts General Hospital between 1980 and 2017. Inclusion criteria were complete medical records outlining clinical course, relevant dental history, and radiographic and microbiologic data. Results Of 167 intracranial abscesses, 88 (52.7%) originated from a head/neck source, and 12 (13.6%) were of odontogenic etiology. Dental radiographs in 7 cases showed active dental infection. The remaining 5 patients reported recent dental procedures. Frontal lobe localization was the most common (7 of 12 [58.3%]). Presenting signs included headache (66.7%), mental status changes (41.6%), visual deficits (41.6%), and speech difficulties (33.3%). Computed tomography (CT) or magnetic resonance imaging (MRI) confirmed all diagnoses. Drainage via open craniotomy was performed in 6 (50%) of 12 patients, and stereotactic CT-guided drainage in 4 (33.3%). The most common pathogens were Streptococcus milleri (45.5%), Staphylococcus species (27.3%), and Fusobacterium (27.3%). All cases had favorable outcomes. Five had residual neurologic deficits, 4 had persistent visual complaints, and a recurrent abscess developed in 1 case. Conclusions These findings showed a higher subset (13.6%) of brain abscesses that could be attributed to odontogenic etiology than previously reported in the literature and highlight the need to rule out dental sources in cryptogenic cases.

Managing the airway of an infant with Pierre Robin sequence (PRS) is particularly challenging for anesthesiologists. Patients with PRS have the triad of micrognathia, glossoptosis, and airway obstruction that potentially and frequently leads to difficulty with both ventilation and intubation. Thus continuous oxygenation and spontaneous ventilation during intubation are essential. We describe a new method to deliver continuous oxygen and volatile anesthetic during nasotracheal intubation in an infant with PRS.

Background and objective In binary classification problems with a rare class of interest, there is relatively little information available for the rare class to build a model. On the other hand, the number of useful variables to develop a model for classification can be high-dimensional. For example, in drug discovery, there are usually a very few bioactive compounds in a large chemical library, whereas thousands of potentially useful explanatory variables characterize a compound's chemical structure. The sparsity of information for the rare class of interest makes it difficult for the standard classification models to exploit the richness of the useful feature variables. Thus, the objective of this paper is to develop an R package which clusters the feature variables into diverse subsets to be aggregated into a powerful ensemble for the detection of a rare class object. Methods The ensemble of phalanxes (EPX) builds a classifier by exploiting the richness of feature variables using several diverse subsets of variables, called phalanxes, and outperforms many competitive state-of-the-art classification methods in terms of predictive ranking of the rare class of interest. Results We present an R package EPX which implements the algorithm to form the ensemble of phalanxes as well as its associated functions. We further show how the ensemble of phalanxes can be constructed using parallel computing to lower the computational burden given high-dimensional data. Conclusions The R package EPX shows a flexible way of clustering feature variable space into smaller and diverse subsets of variables to develop an ensemble of phalanxes which better ranks a rare class object in a highly unbalanced two class classification problem. The ensemble EPX will be useful to detect the rare drug-like active biomolecules for development in drug discovery (Tomal et al., Mar. 2016) [1] and homologous proteins using similarity scores of amino acid sequences in protein homology (Tomal et al., 2019) [2]. The package EPX is freely available to download from CRAN ( https://CRAN.R-project.org/package=EPX ).

Brain tumor patients face a poor prognosis despite significant advances in tumor imaging, neurosurgery and radiation therapy. Potent chemotherapeutic drugs fail when used to treat brain tumors because biochemical and physiological barriers limit drug delivery into the brain. A retro-convection enhanced delivery (R-CED) method has been developed to improve the entry of intravenously administered therapeutics within solid brain tumors. R-CED uses an osmotic gradient to withdraw brain interstitial fluid in a controlled manner via an implanted microdialysis catheter. The transmembrane osmotic gradient increased the local tissue specific gravity in normal brain and induced movement of small proteins and nanoparticulates from the blood into normal brain and an orthotopic 9L tumor. The magnitude of the R-CED effect decreased to control values within six hours and did not cause acute anatomical damage beyond that of probe insertion. A one hour R-CED treatment applied immediately after intravenous injection of liposomal doxorubicin ten days after tumor implantation showed no therapeutic effect compared to animals treated with intravenous PBS alone. The result suggests that R-CED may be more efficacious by modifying the R-CED probe design, increasing the R-CED treatment time, and improving the chemotherapeutic type and dosing schedule. A mathematical model has been developed to predict the size of the R-CED affected region while varying the interstitial and vascular hydraulic conductivity and the fluid removal rate. The model enables the prediction of non-spherical flow patterns during simultaneous R-CED and CED or dual-probe CED via two catheters, guiding probe placement to achieve drug patterning and enabling wide distribution of therapeutics while sparing normal tissues. The alteration of solute flow was confirmed for dual-probe CED in vitro, but was difficult to visualize in vivo, where tissue inhomogeneities altered the flow from the idealized model prediction. These studies demonstrate that R-CED is a viable and well-tolerated technique to enhance the distribution of systemically administered drugs in both the normal tissue-tumor margin as well as the central tumor core. They also highlight the opportunities to modify the R-CED design and enable future drug distribution and antitumor efficacy studies in larger tumors and possibly humans.

Children with difficult airways are particularly vulnerable. Recognition of a potential difficult airway and preparation are the key to caring for them successfully. A simple checklist and teamwork can help optimize care. Introduce all team members, and review the induction and intubation plan with the entire team, including identifying the clinician making each intubation attempt. Identify an individual who is available to assist before beginning airway management. The following principles should guide the care of these patients: 1. Limit the number of tracheal intubation attempts. 2. Know your equipment. Be prepared. 3. Always attempt to oxygenate during intubation. 4. Ensure an adequate depth of anesthesia before instrumenting the airway. 5. Be wary of cognitive biases that may delay action.

Background The novel coronavirus 2019 (COVID-19) pandemic has mobilized global research at an unprecedented scale. While challenges associated with the COVID-19 trial landscape have been discussed previously, no comprehensive reviews have been conducted to assess the reporting, design, and data sharing practices of randomized controlled trials (RCTs). Purpose The purpose of this review was to gain insight into the current landscape of reporting, methodological design, and data sharing practices for COVID-19 RCTs. Data sources We conducted three searches to identify registered clinical trials, peer-reviewed publications, and pre-print publications. Study selection After screening eight major trial registries and 7844 records, we identified 178 registered trials and 38 publications describing 35 trials, including 25 peer-reviewed publications and 13 pre-prints. Data extraction Trial ID, registry, location, population, intervention, control, study design, recruitment target, actual recruitment, outcomes, data sharing statement, and time of data sharing were extracted. Data synthesis Of 178 registered trials, 112 (62.92%) were in hospital settings, median planned recruitment was 100 participants (IQR: 60, 168), and the majority (n = 166, 93.26%) did not report results in their respective registries. Of 35 published trials, 31 (88.57%) were in hospital settings, median actual recruitment was 86 participants (IQR: 55.5, 218), 10 (28.57%) did not reach recruitment targets, and 27 trials (77.14%) reported plans to share data. Conclusions The findings of our study highlight limitations in the design and reporting practices of COVID-19 RCTs and provide guidance towards more efficient reporting of trial results, greater diversity in patient settings, and more robust data sharing.

Primary trigeminal neuralgia is a common clinical refractory neuralgia characterized by an onset of excruciating pain that can severely affect patients’ quality of life. Long-term suffering from this pain may lead to depression, anxiety, and suicide. Current treatments, however, are associated with high recurrent rates and severe complications. We hypothesize that both the applicability and efficacy of magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) treatment in primary trigeminal neuralgia can be achieved under the following conditions: a specific target focus and incident channel, a temperature measurement system that does not incur damage to surrounding tissues, and an optimal radiation dose. Successful non-invasive treatment of primary trigeminal neuralgia by MR-HIFU systems could represent a breakthrough of this technology applied to the oral and maxillofacial region.

BACKGROUND: Complex cranial vault reconstruction (CCVR) often requires a large-volume transfusion of blood products. We implemented a series of improvement interventions to reduce blood donor exposures (BDE) and transfusion requirements in CCVR. METHODS: We implemented interventions over 4 epochs: (E1) reconstituted blood (1:1 ratio of donor-matched red blood cells and fresh-frozen plasma) for intraoperative transfusions, (E2) reconstituted blood plus postoperative transfusion guidelines, (E3) reconstituted blood plus intraoperative antifibrinolytics and postoperative guidelines, and (E4) fresh whole blood for intraoperative transfusion, antifibrinolytics, and postoperative guidelines. Primary outcomes, BDE, and total volume of blood products transfused are presented by using statistical process control charts, with statistical comparisons between each epoch and baseline data. RESULTS: We included 347 patients CONCLUSIONS: The implementation of sequential clinical improvement strategies resulted in a sustained reduction in BDE whereas only the use of whole blood resulted in a significant reduction in the total volume of blood products transfused in children undergoing CCVR.

Objectives This study aimed to characterize the use of cardiovascular testing for patients with incident heart failure (HF) hospitalization who participated in the National Heart, Lung, and Blood Institute sponsored Cardiovascular Research Network (CVRN) Heart Failure study. Background HF is a common cause of hospitalization, and testing and treatment patterns may differ substantially between providers. Testing choices have important implications for the cost and quality of care. Methods Crude and adjusted cardiovascular testing rates were calculated for each participating hospital. Cox proportional hazards regression models were used to examine hospital testing rates after adjustment for hospital-level patient case mix. Results Of the 37,099 patients in the CVRN Heart Failure study, 5,878 patients were hospitalized with incident HF between 2005 and 2008. Of these, evidence of cardiovascular testing was available for 4,650 (79.1%) patients between 14 days before the incident HF admission and ending 6 months after the incident discharge. We compared crude and adjusted cardiovascular testing rates at the hospital level because the majority of testing occurred during the incident HF hospitalization. Of patients who underwent testing, 4,085 (87.9%) had an echocardiogram, 4,345 (93.4%) had a systolic function assessment, and 1,714 (36.9%) had a coronary artery disease assessment. Crude and adjusted testing rates varied markedly across the profiled hospitals, for individual testing modalities (e.g., echocardiography, stress echocardiography, nuclear stress testing, and left heart catheterization) and for specific clinical indications (e.g., systolic function assessment and coronary artery disease assessment). Conclusions For patients with newly diagnosed HF, we did not observe widespread overuse of cardiovascular testing in the 6 months following incident HF hospitalization relative to existing HF guidelines. Variations in testing were greatest for assessment of ischemia, in which testing guidelines are less certain.

Neonates are a patient population with special considerations in relation to blood transfusion. Preterm neonates are among the most frequently transfused patient groups. Because of advances in neonatal intensive care, including advances in blood component administration, smaller and more premature infants are surviving. This chapter discusses blood components and their suggested indications for transfusion in neonates and reviews vascular access, blood product filters, and warmers. This chapter also presents the use of antifibrinolytics and perioperative transfusion monitoring in neonates.

Background— There is scant evidence on the effect that chronic kidney disease (CKD) confers on clinically meaningful outcomes among patients with heart failure with preserved left ventricular ejection fraction (HF-PEF). Methods and Results— We identified a community-based cohort of patients with HF. Electronic medical record data were used to divide into HF-PEF and reduced left ventricular EF on the basis of quantitative and qualitative estimates. Level of CKD was assessed by estimated glomerular filtration rate (eGFR) and by dipstick proteinuria. We followed patients for a median of 22.1 months for outcomes of death and hospitalization (HF-specific and all-cause). Multivariable Cox regression estimated the adjusted relative-risk of outcomes by level of CKD, separately for HF-PEF and HF with reduced left ventricular EF. We identified 14 579 patients with HF-PEF and 9762 with HF with reduced left ventricular EF. When compared with patients with eGFR between 60 and 89 mL/min per 1.73 m 2 , lower eGFR was associated with an independent graded increased risk of death and hospitalization. For example, among patients with HF-PEF, the risk of death was nearly double for eGFR 15 to 29 mL/min per 1.73 m 2 and 7× higher for eGFR2 , with similar findings in those with HF with reduced left ventricular EF. Conclusions— CKD is common and an important independent predictor of death and hospitalization in adults with HF across the spectrum of left ventricular systolic function. Our study highlights the need to develop new and effective interventions for the growing number of patients with HF complicated by CKD.

Limited data exist describing the differences in the medical treatment of patients with heart failure with preserved ejection fraction (HF-PEF) from those with heart failure with reduced ejection fraction (HF-REF) in more generalizable population-based cohorts. We studied patients with incident HF diagnosed from 2005 to 2008 from 4 sites participating in the Cardiovascular Research Network. These patients, their medication profile, and left ventricular systolic function status were identified from the hospital discharge and ambulatory visit diagnoses, pharmacy dispensing information, and imaging reports found in the health plan electronic databases and through chart review. The study population consisted of 6,210 patients with newly diagnosed HF-PEF and 3,914 patients with newly diagnosed HF-REF. The mean age of our study population was 73 years, 48% were women, and 74% were white. The patients with HF-REF were less likely to have been treated with various cardiac and HF-related medications before their index HF event; however, they were significantly more likely to have been treated with new cardiac medications and HF therapies after the diagnosis of HF than were the patients with HF-PEF. After controlling for several potentially confounding factors, the patients with HF-PEF were significantly less likely to have been treated with multiple cardiac drug regimens (adjusted odds ratio 0.69, 95% confidence interval 0.59 to 0.81) and multiple HF-related therapies (adjusted odds ratio 0.40, 95% confidence interval 0.38 to 0.42) than were patients with HF-REF. In conclusion, the present results from a large, population-based sample suggest considerable variation in the previous and new use of different cardiac medication classes of drugs in patients with HF-PEF versus HF-REF.

Terrestrial gastropods have been shown to exert major impacts on the plant structure and species composition of temperate grasslands and other terrestrial plant communities. In order to develop predictions of plant community responses to changing environments, it is critical to understand how factors structuring plant communities will be influenced by global changes. Nevertheless, little is known about the potential for the size and abundance of gastropods to be altered by the individual and combined effects of elevated atmospheric CO 2 and increased deposition of N. Previous work suggests that responses of herbivore abundance to these global changes seem likely to depend, in part, upon the changes in the quantity of plant biomass available for consumption, and changes in the nutritional quality of this plant material for gastropod survival, development, and reproduction. Therefore, in this study we investigated the effect of elevated CO 2 and increased N deposition on gastropod size and abundance, as well as the effects on plant community production and N status. Elevated CO 2 depressed the size of gastropods early in the growing season by 29% to 42%, increased mid-season gastropod abundance by 38% to 43%, and depressed abundance late in the growing season by 21% to 29%. These changes in gastropod size and abundance were due largely to the modification of plant tissue quality and quantity. Increased N deposition, in contrast, influenced neither gastropod abundance nor per capita biomass during any part of the growing season. Neither elevated CO 2 nor increased N deposition disrupted the temporal synchrony between plant production and slug abundance.

Transcranial electrical motor-evoked potential (tceMEP) monitoring is used in complex intracranial and spinal surgeries to detect and prevent neurological injury. We present a case of transient, reproducible loss of tceMEPs after an infusion of levetiracetam during craniotomy and tumor resection in a child. Cessation of the infusion resulted in restoration of baseline tceMEPs. When the infusion was resumed at the end of the procedure, a similar decrease in tceMEPs was seen as before, after the infusion was stopped. The surgery and postoperative course proceeded without incident, and the patient experienced a full recovery.

Background An improved understanding of racial differences in the natural history, clinical characteristics, and outcomes of heart failure will have important clinical and public health implications. We assessed how clinical characteristics and outcomes vary across racial groups (whites, blacks, and Asians) in adults with heart failure with preserved ejection fraction. Methods We identified all adults with heart failure with preserved ejection fraction between 2005 and 2008 from 4 health systems in the Cardiovascular Research Network using hospital principal discharge and ambulatory visit diagnoses. Results Among 13,437 adults with confirmed heart failure with preserved ejection fraction, 85.9% were white, 7.6% were black, and 6.5% were Asian. After adjustment for potential confounders and use of cardiovascular therapies, compared with whites, blacks (adjusted hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.62-0.85) and Asians (HR, 0.75; 95% CI, 0.64-0.87) had a lower risk of death from any cause. Compared with whites, blacks had a higher risk of hospitalization for heart failure (HR, 1.48; 95% CI, 1.29-1.68); no difference was observed for Asians compared with whites (HR, 1.01; 95% CI, 0.86-1.18). Compared with whites, no significant differences were detected in risk of hospitalization for any cause for blacks (HR, 1.03; 95% CI, 0.95-1.12) and Asians (HR, 0.93; 95% CI, 0.85-1.02). Conclusions In a diverse population with heart failure with preserved ejection fraction, we observed complex relationships between race and important clinical outcomes. More detailed studies of large populations are needed to fully characterize the epidemiologic picture and to elucidate potential pathophysiologic and treatment-response differences that may relate to race.

Background/AimsAtrial fibrillation (AF) and heart failure (HF) are two of the most common cardiovascular conditions nationally and AF frequently complicates HF. We examined how AF impacts adverse outcomes in HF with preserved left ventricular ejection fraction (HF-PEF) vs. reduced ejection fraction (HF-REF) within a large, contemporary cohort.MethodsWe identified all adults diagnosed with HF-PEF or HF-REF based on hospital discharge and ambulatory visit diagnoses and relevant imaging results between 2005–2008 from four health plans in the Cardiovascular Research Network. Data on demographic features, diagnoses, procedures, outpatient pharmacy use, and laboratory results were ascertained from health plan databases. Hospitalizations for HF, stroke, and any other reason were identified from hospital discharge and billing claims databases. Deaths were ascertained from health plan and state death files.ResultsAmong 23,644 patients with HF, 11,429 (48.3%) had documented AF (9,081 pre-existing, 2,348 incident). Compared with patients who did not have AF, patients with AF had higher adjusted rates of ischemic stroke (hazard ratio [HR] 2.47 for incident AF; HR 1.57 for pre-existing AF), hospitalization for HF (HR 2.00 for incident AF; HR 1.22 for pre-existing AF), all-cause hospitalization (HR 1.45 for incident AF; HR 1.15 for pre-existing AF), and death (incident AF HR 1.67; pre-existing AF HR 1.13). The associations of AF with these outcomes were similar for HF-PEF and HF-REF, with the exception of ischemic stroke.ConclusionsAF is a potent risk factor for adverse outcomes in patients with HF-PEF or HF-REF. Effective interventions are needed to improve the prognosis of these high-risk patients.

Background— Although heart failure (HF) is a syndrome with important differences in response to therapy by left ventricular ejection fraction (LVEF), existing risk stratification models typically group all HF patients together. The relative importance of common predictor variables for important clinical outcomes across strata of LVEF is relatively unknown. Methods and Results— We identified all members with HF between 2005 and 2008 from 4 integrated healthcare systems in the Cardiovascular Research Network. LVEF was categorized as preserved (LVEF ≥50% or normal), borderline (41%–49% or mildly reduced), and reduced (≤40% or moderately to severely reduced). We used Cox regression models to identify independent predictors of death and hospitalization by LVEF category. Among 30 094 ambulatory adults with HF, mean age was 74 years and 46% were women. LVEF was preserved in 49.5%, borderline in 16.2%, and reduced in 34.3% of patients. During a median follow-up of 1.8 years (interquartile range, 0.8–3.1), 8060 (26.8%) patients died, 8108 (26.9%) were hospitalized for HF, and 20 272 (67.4%) were hospitalized for any reason. In multivariable models, nearly all tested covariates performed similarly across LVEF strata for the outcome of death from any cause, as well as for HF-related and all-cause hospitalizations. Conclusions— We found that in a large, diverse contemporary HF population, risk assessment was strikingly similar across all LVEF categories. These data suggest that, although many HF therapies are uniquely applied to patients with reduced LVEF, individual prognostic factor performance does not seem to be significantly related to level of left ventricular systolic function.