Patient and Operative Factors Predict Risk of Discretionary Prolonged Postoperative Mechanical Ventilation in a Broad Surgical Cohort.

BACKGROUND: Patients undergoing surgery with general anesthesia and endotracheal intubation are ideally extubated upon case completion, as prolonged postoperative mechanical ventilation (PPMV) has been associated with poor outcomes. However, some patients require PPMV for surgical reasons, such as airway compromise, while others remain intubated at the discretion of the anesthesia provider. Incidence and risk factors for discretionary PPMV (DPPMV) have been described in individual surgical subspecialties and intensive care unit (ICU) populations, but are relatively understudied in a broad surgical cohort. The present study seeks to fill this gap and identify the perioperative risk factors that predict DPPMV. METHODS: After obtaining institutional review board (IRB) exemption, existing electronic health record databases at our large referral center were retrospectively queried for adult surgeries performed between January 2018 and December 2020 with general anesthesia, endotracheal intubation, and by surgical services that do not routinely leave patients intubated for surgical reasons. Patients who arrived to the ICU intubated after surgery were identified as experiencing DPPMV. Selection of candidate risk factors was performed with LASSO-regularized logistic regression, and surviving variables were used to generate a multivariable logistic regression model of DPPMV risk. RESULTS: A total of 32,915 cases met inclusion criteria, of which 415 (1.26%) experienced DPPMV. Compared to extubated patients, those with DPPMV were more likely to have undergone emergency surgery (42.9% versus 3.4%; P < .001), surgery during an existing ICU stay (30.8% versus 2.8%; P < 0.001), and have 20 of the 31 elixhauser comorbidities ( P < .05 for each comparison), among other differences. A risk model with 12 variables, including American Society of Anesthesiologists (ASA) physical classification status, emergency surgery designation, four Elixhauser comorbidities, surgery during an existing ICU stay, surgery duration, estimated number of intraoperative handoffs, and vasopressor, sodium bicarbonate, and albuterol administration, yielded an area under the receiver operating characteristic curve of 0.97 (95% confidence interval, 0.96-0.97) for prediction of DPPMV. CONCLUSIONS: DPPMV was uncommon in this broad surgical cohort but could be accurately predicted using readily available patient-specific and operative factors. These results may be useful for preoperative risk stratification, postoperative resource allocation, and clinical trial planning.

Reliability of the ASA Physical Status Classification System in Predicting Surgical Morbidity: a Retrospective Analysis.

The American Society of Anesthesiologists (ASA) Physical Status Classification System has been used to assess pre-anesthesia comorbid conditions for over 60 years. However, the ASA Physical Status Classification System has been criticized for its subjective nature. In this study, we aimed to assess the correlation between the ASA physical status assignment and more objective measures of overall illness. This is a single medical center, retrospective cohort study of adult patients who underwent surgery between November 2, 2017 and April 22, 2020. A multivariable ordinal logistic regression model was developed to examine the relationship between the ASA physical status and Elixhauser comorbidity groups. A secondary analysis was then conducted to evaluate the capability of the model to predict 30-day postoperative mortality. A total of 56,820 cases meeting inclusion criteria were analyzed. Twenty-seven Elixhauser comorbidities were independently associated with ASA physical status. Older patient (adjusted odds ratio, 1.39 [per 10 years of age]; 95% CI 1.37 to 1.41), male patient (adjusted odds ratio, 1.24; 95% CI 1.20 to 1.29), higher body weight (adjusted odds ratio, 1.08 [per 10 kg]; 95% CI 1.07 to 1.09), and ASA emergency status (adjusted odds ratio, 2.11; 95% CI 2.00 to 2.23) were also independently associated with higher ASA physical status assignments. Furthermore, the model derived from the primary analysis was a better predictor of 30-day mortality than the models including either single ASA physical status or comorbidity indices in isolation (p < 0.001). We found significant correlation between ASA physical status and 27 of the 31 Elixhauser comorbidities, as well other demographic characteristics. This demonstrates the reliability of ASA scoring and its potential ability to predict postoperative outcomes. Additionally, compared to ASA physical status and individual comorbidity indices, the derived model offered better predictive power in terms of short-term postoperative mortality.

Etiology and Timing of Postoperative Rapid Response Team Activations.

In this retrospective cohort study we sought to evaluate the association between the etiology and timing of rapid response team (RRT) activations in postoperative patients at a tertiary care hospital in the southeastern United States. From 2010 to 2016, there were 2,390 adult surgical inpatients with RRT activations within seven days of surgery. Using multivariable linear regression, we modeled the correlation between etiology of RRT and timing of the RRT call, as measured from the conclusion of the surgical procedure. We found that respiratory triggers were associated with an increase in time after surgical procedure to RRT of 10.6 h compared to activations due to general concern (95% CI 3.9 - 17.3) (p = 0.002). These findings may have an impact on monitoring of postoperative patients, as well as focusing interventions to better respond to clinically deteriorating patients.

Observational Study of Clinician Attentional Reserves (OSCAR): Acuity-Based Rounds Help Preserve Clinicians' Attention.

OBJECTIVES: Team rounding in the ICU can tax clinicians' finite attentional resources. We hypothesized that a novel approach to rounding, where patients are seen in a decreasing order of acuity, would decrease attentional attrition. DESIGN: Prospective interventional internal-control cohort study in which stop signal task testing was used as a proxy for attentional reserves. Stop signal task is a measure of cognitive control and response inhibition in addition to performance monitoring, all reflective of executive control abilities, and our surrogate for attentional reserves. SETTING: The ICUs of Vanderbilt University Medical Center (site 1) and the University of Pennsylvania (site 2) from November 2014 to August 2017. SUBJECTS: Thirty-three clinicians at site 1, and 24 clinicians at site 2. INTERVENTIONS: Acuity-based rounding, in which clinicians round from highest to lowest acuity as determined by Sequential Organ Failure Assessment score or an equivalent acuity score. MEASUREMENTS AND MAIN RESULTS: The stop signal task results of ICU staff at two sites were compared for conventional (in room order) versus novel (in decreasing order of acuity) rounding order. At site 1, the difference in stop signal reaction time change between two rounding types was -39.0 ms (95% CI, -50.6 to -27.4 ms; p < 0.001), and at site 2, the performance stop signal reaction time was -15.6 ms (95% CI, -29.1 to -2.1 ms; p = 0.023). These sub-second changes, while small, are significant in the neuroscience domain. CONCLUSIONS: Rounding in decreasing order of patient acuity mitigated attrition in attentional reserves when compared with the traditional rounding method.

Development and Validation of an Automated Tool to Retrieve and Curate Faculty Publications of Academic Departments.

Introduction Academic departments need to monitor their faculty's academic productivity for various purposes, such as reporting to the medical school dean, assessing the allocation of non-clinical research time, evaluating for rank promotion, and reporting to the Accreditation Council for Graduate Medical Education (ACGME). Our objective was to develop and validate a simple method that automatically generates query strings to identify and process distinct department faculty publications listed in PubMed and Scopus. Methods We created a macro-enabled Excel workbook (Microsoft, Redmond, WA) to automate the retrieval of faculty publications from the PubMed and Scopus bibliometric databases (available at https://bit.ly/get-pubs). Where the returned reference includes the digital object identifier (doi), a link is provided in the workbook. Duplicate publications are removed automatically, and false attributions are managed. Results At the University of Miami, between 2020 and 2021, there were 143 anesthesiology faculty-authored publications with a PubMed identifier (PMID), 95.8% identified by the query and 4.2% missed. At Vanderbilt University Medical Center, between 2019 and 2021, there were 760 anesthesiology faculty-authored publications with a PMID, 94.3% identified by the query and 5.7% missed. Recall, precision, and the F1 score were all above 93% at both medical centers. Conclusions We developed a highly accurate, simple, transportable, scalable method to identify publications in PubMed and Scopus authored by anesthesiology faculty. Manual checking and faculty feedback are required because not all names can be disambiguated, and some references are missed. This process can greatly reduce the burden of curating a list of faculty publications. The methodology applies to other academic departments that track faculty publications.

Leukemogenic transformation by HOXA cluster genes.

HOX homeobox genes are important regulators of normal and malignant hematopoiesis. Abdominal-type HOXA genes like HOXA9 are highly leukemogenic. However, little is known about transformation by anterior HOXA genes. Here we performed a comprehensive assessment of the oncogenic potential of every HOXA gene in primary hematopoietic cells. With exception of HOXA2 and HOXA5, all HOXA genes caused a block or delay of hematopoietic differentiation and cooperated with Meis1. No evidence for the alleged tumor-suppressor function of HOXA5 could be found. Whereas all active HOXA genes immortalized mixed granulocytic/monocytic populations, HOXA13 preferentially specified monocytoid development. The anterior HOXA genes HOXA1, HOXA4, and HOXA6 transformed cells, generating permanent cell lines, although they did so less potently than HOXA9. Upon transplantation these lines induced myeloproliferation and acute myeloid leukemia in recipient animals. Kinetic studies with inducible HOX derivatives demonstrated that anterior HOXA genes autonomously contributed to cellular transformation. This function was not mediated by endogenous Hoxa9, which was persistently expressed in cells transformed by anterior HOX genes. In summary our results demonstrate a hitherto unexpected role of anterior HOXA genes in hematopoietic malignancy.

Misguided transcriptional elongation causes mixed lineage leukemia.

Fusion proteins composed of the histone methyltransferase mixed-lineage leukemia (MLL) and a variety of unrelated fusion partners are highly leukemogenic. Despite their prevalence, particularly in pediatric acute leukemia, many molecular details of their transforming mechanism are unknown. Here, we provide mechanistic insight into the function of MLL fusions, demonstrating that they capture a transcriptional elongation complex that has been previously found associated with the eleven-nineteen leukemia protein (ENL). We show that this complex consists of a tight core stabilized by recursive protein-protein interactions. This central part integrates histone H3 lysine 79 methylation, RNA Polymerase II (RNA Pol II) phosphorylation, and MLL fusion partners to stimulate transcriptional elongation as evidenced by RNA tethering assays. Coimmunoprecipitations indicated that MLL fusions are incorporated into this complex, causing a constitutive recruitment of elongation activity to MLL target loci. Chromatin immunoprecipitations (ChIP) of the homeobox gene A cluster confirmed a close relationship between binding of MLL fusions and transcript levels. A time-resolved ChIP utilizing a conditional MLL fusion singled out H3K79 methylation as the primary parameter correlated with target expression. The presence of MLL fusion proteins also kept RNA Pol II in an actively elongating state and prevented accumulation of inhibitory histone methylation on target chromatin. Hox loci remained open and productive in the presence of MLL fusion activity even under conditions of forced differentiation. Finally, MLL-transformed cells were particularly sensitive to pharmacological inhibition of RNA Pol II phosphorylation, pointing to a potential treatment for MLL. In summary, we show aberrant transcriptional elongation as a novel mechanism for oncogenic transformation.

Anesthetic Considerations for Functional Neurosurgery.

Functional neurosurgery is a rapidly growing field that uses surgical resection, ablation, or neuromodulation to treat an assortment of neurologic and psychiatric disorders, the most common of which are movement disorders and epilepsy. Anesthesiologists caring for patients undergoing neurofunctional procedures should be aware of the anesthetic implications of patients' underlying disease as well as procedure-specific concerns, such as the effects of anesthetics on intraoperative neuromonitoring and limited access to patients due to stereotactic frames or intraoperative imaging.

Natural Language Mapping of Electrocardiogram Interpretations to a Standardized Ontology.

BACKGROUND: Interpretations of the electrocardiogram (ECG) are often prepared using software outside the electronic health record (EHR) and imported via an interface as a narrative note. Thus, natural language processing is required to create a computable representation of the findings. Challenges include misspellings, nonstandard abbreviations, jargon, and equivocation in diagnostic interpretations. OBJECTIVES: Our objective was to develop an algorithm to reliably and efficiently extract such information and map it to the standardized ECG ontology developed jointly by the American Heart Association, the American College of Cardiology Foundation, and the Heart Rhythm Society. The algorithm was to be designed to be easily modifiable for use with EHRs and ECG reporting systems other than the ones studied. METHODS: An algorithm using natural language processing techniques was developed in structured query language to extract and map quantitative and diagnostic information from ECG narrative reports to the cardiology societies' standardized ECG ontology. The algorithm was developed using a training dataset of 43,861 ECG reports and applied to a test dataset of 46,873 reports. RESULTS: Accuracy, precision, recall, and the F1-measure were all 100% in the test dataset for the extraction of quantitative data (e.g., PR and QTc interval, atrial and ventricular heart rate). Performances for matches in each diagnostic category in the standardized ECG ontology were all above 99% in the test dataset. The processing speed was approximately 20,000 reports per minute. We externally validated the algorithm from another institution that used a different ECG reporting system and found similar performance. CONCLUSION: The developed algorithm had high performance for creating a computable representation of ECG interpretations. Software and lookup tables are provided that can easily be modified for local customization and for use with other EHR and ECG reporting systems. This algorithm has utility for research and in clinical decision-support where incorporation of ECG findings is desired.

Rethinking Clinical Workflow.

The concept of clinical workflow borrows from management and leadership principles outside of medicine. The only way to rethink clinical workflow is to understand the neuroscience principles that underlie attention and vigilance. With any implementation to improve practice, there are human factors that can promote or impede progress. Modulating the environment and working as a team to take care of patients is paramount. Clinicians must continually rethink clinical workflow, evaluate progress, and understand that other industries have something to offer. Then, novel approaches can be implemented to take the best care of patients.

The Oncogenic Transcription Factor RUNX1/ETO Corrupts Cell Cycle Regulation to Drive Leukemic Transformation.

Oncogenic transcription factors such as the leukemic fusion protein RUNX1/ETO, which drives t(8;21) acute myeloid leukemia (AML), constitute cancer-specific but highly challenging therapeutic targets. We used epigenomic profiling data for an RNAi screen to interrogate the transcriptional network maintaining t(8;21) AML. This strategy identified Cyclin D2 (CCND2) as a crucial transmitter of RUNX1/ETO-driven leukemic propagation. RUNX1/ETO cooperates with AP-1 to drive CCND2 expression. Knockdown or pharmacological inhibition of CCND2 by an approved drug significantly impairs leukemic expansion of patient-derived AML cells and engraftment in immunodeficient murine hosts. Our data demonstrate that RUNX1/ETO maintains leukemia by promoting cell cycle progression and identifies G1 CCND-CDK complexes as promising therapeutic targets for treatment of RUNX1/ETO-driven AML.

Outbreak report of airborne caterpillar dermatitis in a kindergarten.

BACKGROUND: The oak processionary caterpillar is found in several European countries. The larva of Thaumetopoea processionea Lepidoptera from the third to sixth larval instar develops poisonous hair (setae), filled with an urticating toxin that could lead to serious dermatitis, conjunctivitis and pulmonary problems (summarized as lepidopterism) on contact. OBJECTIVES: To determine the incidence of caterpillar dermatitis in a kindergarten population with three infested oak trees located in its enclosure. METHODS: We made a survey by the use of a questionnaire that was handed out to all parents with children regularly visiting that kindergarten. RESULTS: Twenty-four out of 47 (51%) questionnaires were returned and 10/24 (42%) children showing symptoms of lepidopterism were reported: 8/10 (80%) dermatitis, 5/10 (50%) pruritus, 5/10 (50%) respiratory distress, 4/10 (40%) malaise and/or fever and 1/10 (10%) conjunctivitis. Seven out of 10 visited a physician but the correct diagnosis was not posed in any case. Four out of 7 received medication (topical and/or systemic antihistaminics and/or steroids). CONCLUSIONS: Lepidopterism, an airborne disease caused by the setae of the processionary caterpillar, is a growing public health problem because of the increasing numbers of outbreaks, and it is still underestimated. Children seem to suffer more often from general symptoms and airway affection than adults.

[Nevoid basal cell carcinoma syndrome]. / Naevoid Basalzellkarzinom-syndrom.

Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is an autosomal-dominant disorder characterized by multiple basal cell carcinomas, jaw cysts, palmar/plantar pits, calcification of the falx cerebri, and spine and rib anomalies. The combination of clinical, imaging, and histological findings is helpful in identifying NBCCS patients. Imaging plays a crucial role in evaluation of these patients. We present a wide variety of clinical and radiological findings characteristic of this disease.

A role for the MLL fusion partner ENL in transcriptional elongation and chromatin modification.

Chimeric proteins joining the histone methyltransferase MLL with various fusion partners trigger distinctive lymphoid and myeloid leukemias. Here, we immunopurified proteins associated with ENL, a protein commonly fused to MLL. Identification of these ENL-associated proteins (EAPs) by mass spectrometry revealed enzymes with a known role in transcriptional elongation (RNA polymerase II C-terminal domain kinase [RNAPolII CTD] positive transcription elongation factor b [pTEFb]), and in chromatin modification (histone-H3 methyltransferase DOT1L) as well as other frequent MLL partners (AF4, AF5q31, and LAF4), and polycomb group members (RING1, CBX8, and BCoR). The composition of EAP was further verified by coimmunoprecipitation, 2-hybrid analysis, pull-down, and colocalization experiments. Purified EAP showed a histone H3 lysine 79-specific methylase activity, displayed a robust RNAPolII CTD kinase function, and counteracted the effect of the pTEFb inhibitor 5,6-dichloro-benzimidazole-riboside. In vivo, an ENL knock-down diminished genome-wide as well as gene-specific H3K79 dimethylation, reduced global run-on elongation, and inhibited transient transcriptional reporter activity. According to structure-function data, DOT1L recruitment was important for transformation by the MLL-ENL fusion derivative. These results suggest a function of ENL in histone modification and transcriptional elongation.