Use of an Asynchronous Discussion Platform During the Pre-clerkship Curriculum: A Multiyear Retrospective Study.

Introduction: Asynchronous online message boards (OMBs) allow users to write questions or comments and share them with an online group. While the use of OMBs has been associated with positive outcomes in several educational settings, their use has not been studied in pre-clerkship undergraduate medical education (UME). Methods: This multiyear, observational, longitudinal study examined patterns of OMB use in pre-clerkship UME. Descriptive statistics were used to report the number of students and instructors who logged on and contributed, the number of posts, instructor answers, post views, and the average time to answer. Patterns of use by first- and second-year medical students as well as students undergoing remote versus in-person learning were compared using Wilcoxon signed-rank tests. Results: A total of 9870 posts were made to OMBs, initiated by 3869 student questions. There were 3078 total posts made by instructors and academic support staff and 1024 student answers to student questions. First-year medical students posted significantly more questions (149.83 vs. 83.7, p < 0.001), which resulted in significantly more instructor answers (125.0 vs. 59.1, p < 0.001). Modules during the remote learning period received more student questions (152.0 vs. 96.7, p < 0.001) and produced more instructor answers (123.8 vs. 74.7, p < 0.001) as compared to modules that took place during in-person learning. Discussion: Online message boards represent a readily available tool to stimulate asynchronous discussion in pre-clerkship UME. First-year medical students and students during remote learning were more active on OMBs.

Development of a Simulation-Based Mastery Learning Curriculum for Late Goals of Care Discussions.

INTRODUCTION: Fellows in critical care medicine (CCM) routinely help patients and families navigate complex decisions near the end of life. These "late goals of care" (LGOC) discussions require rigorous skills training and impact patient care. Innovation is needed to ensure that fellow training in leading these discussions is centered on reproducible competency-based standards. The aims of this study were to (1) describe the development of a simulation-based mastery learning (SBML) curriculum for LGOC discussions and (2) set a defensible minimum passing standard (MPS) to ensure uniform skill acquisition among learners. INNOVATION: We developed an SBML curriculum for CCM fellows structured around REMAP, a mnemonic outlining foundational components of effective communication around serious illness. A multidisciplinary expert panel iteratively created an LGOC discussion assessment tool. Pilot testing was completed to refine the checklist, set the MPS, and assess skill acquisition. OUTCOMES: The LGOC discussion assessment tool included an 18-item checklist and 6 scaled items. The tool produced reliable data (k ≥ 0.7 and ICC of ≥ 0.7). Using the Mastery Angoff method, the panel set the MPS at 87%. Ten CCM fellows participated in the pilot study. Performance on the checklist significantly improved from a median score of 52% (IQR 44%-72%) at pretest to 96% (IQR 82%-97%) at post-test (P = 0.005). The number of learners who met the MPS similarly improved from 10% during pre-testing to 70% during post-testing (P = 0.02). COMMENT: We describe the development of a LGOC SBML curriculum for CCM fellows which includes a robust communication skills assessment and the delineation of a defensible MPS.

An observational cohort study of bronchoalveolar lavage fluid galactomannan and Aspergillus culture positivity in patients requiring mechanical ventilation.

Rationale: Critically ill patients who develop invasive pulmonary aspergillosis (IPA) have high mortality rates despite antifungal therapy. Diagnosis is difficult in these patients. Bronchoalveolar lavage (BAL) fluid galactomannan (GM) is a helpful marker of infection, although the optimal cutoff for IPA is unclear. We aimed to evaluate the BAL fluid GM and fungal culture results, demographics, and outcomes among a large cohort of mechanically ventilated patients with suspected pneumonia. Methods: A single-center cohort study of patients enrolled in the Successful Clinical Response in Pneumonia Therapy (SCRIPT) study from June 2018 to March 2023. Demographics, BAL results, and outcomes data were extracted from the electronic health record and compared between groups of patients who grew Aspergillus on a BAL fluid culture, those who had elevated BAL fluid GM levels (defined as >0.5 or >0.8) but did not grow Aspergillus on BAL fluid culture, and those with neither. Results: Of over 1700 BAL samples from 688 patients, only 18 BAL samples grew Aspergillus. Patients who had a BAL sample grow Aspergillus (n=15) were older (median 71 vs 62 years, p=0.023), had more days intubated (29 vs 11, p=0.002), and more ICU days (34 vs 15, p=0.002) than patients whose BAL fluid culture was negative for Aspergillus (n=672). The BAL fluid galactomannan level was higher from samples that grew Aspergillus on culture than those that did not (median ODI 7.08 vs 0.11, p<0.001), though the elevation of BAL fluid GM varied across BAL samples for patients who had serial sampling. Patients who grew Aspergillus had a similar proportion of underlying immunocompromise compared with the patients who did not, and while no statistically significant difference in overall unfavorable outcome, had longer duration of ventilation and longer ICU stays. Conclusions: In this large cohort of critically ill patients with a high number of BAL samples with GM levels, we found a relatively low rate of Aspergillus growth. Patients who eventually grew Aspergillus had inconsistently elevated BAL fluid GM, and many patients with elevated BAL fluid GM did not grow Aspergillus. These data suggest that the pre-test probability of invasive pulmonary aspergillosis should be considered low in a general ICU population undergoing BAL evaluation to define the etiology of pneumonia. Improved scoring systems are needed to enhance pre-test probability for diagnostic test stewardship purposes.

Clinical significance of culture-negative, PCR-positive bronchoalveolar lavage results in severe pneumonia.

Some culture-negative, PCR-positive BAL samples may represent true infection. A subset of patients with a culture-negative, PCR-positive BAL result will have a subsequent BAL culture positive for the organism initially identified by PCR alone. https://bit.ly/3DWoFPo.

Improved genomic prediction using machine learning with Variational Bayesian sparsity.

BACKGROUND: Genomic prediction has become a powerful modelling tool for assessing line performance in plant and livestock breeding programmes. Among the genomic prediction modelling approaches, linear based models have proven to provide accurate predictions even when the number of genetic markers exceeds the number of data samples. However, breeding programmes are now compiling data from large numbers of lines and test environments for analyses, rendering these approaches computationally prohibitive. Machine learning (ML) now offers a solution to this problem through the construction of fully connected deep learning architectures and high parallelisation of the predictive task. However, the fully connected nature of these architectures immediately generates an over-parameterisation of the network that needs addressing for efficient and accurate predictions. RESULTS: In this research we explore the use of an ML architecture governed by variational Bayesian sparsity in its initial layers that we have called VBS-ML. The use of VBS-ML provides a mechanism for feature selection of important markers linked to the trait, immediately reducing the network over-parameterisation. Selected markers then propagate to the remaining fully connected feed-forward components of the ML network to form the final genomic prediction. We illustrated the approach with four large Australian wheat breeding data sets that range from 2665 lines to 10375 lines genotyped across a large set of markers. For all data sets, the use of the VBS-ML architecture improved genomic prediction accuracy over legacy linear based modelling approaches. CONCLUSIONS: An ML architecture governed under a variational Bayesian paradigm was shown to improve genomic prediction accuracy over legacy modelling approaches. This VBS-ML approach can be used to dramatically decrease the parameter burden on the network and provide a computationally feasible approach for improving genomic prediction conducted with large breeding population numbers and genetic markers.

An Adjudication Protocol for Severe Pneumonia.

Background: Clinical end points that constitute successful treatment in severe pneumonia are difficult to ascertain and vulnerable to bias. The utility of a protocolized adjudication procedure to determine meaningful end points in severe pneumonia has not been well described. Methods: This was a single-center prospective cohort study of patients with severe pneumonia admitted to the medical intensive care unit. The objective was to develop an adjudication protocol for severe bacterial and/or viral pneumonia. Each episode of pneumonia was independently reviewed by 2 pulmonary and critical care physicians. If a discrepancy occurred between the 2 adjudicators, a third adjudicator reviewed the case. If a discrepancy remained after all 3 adjudications, consensus was achieved through committee review. Results: Evaluation of 784 pneumonia episodes during 593 hospitalizations achieved only 48.1% interobserver agreement between the first 2 adjudicators and 78.8% when agreement was defined as concordance between 2 of 3 adjudicators. Multiple episodes of pneumonia and presence of bacterial/viral coinfection in the initial pneumonia episode were associated with lower interobserver agreement. For an initial episode of bacterial pneumonia, patients with an adjudicated day 7-8 clinical impression of cure (compared with alternative impressions) were more likely to be discharged alive (odds ratio, 6.3; 95% CI, 3.5-11.6). Conclusions: A comprehensive adjudication protocol to identify clinical end points in severe pneumonia resulted in only moderate interobserver agreement. An adjudicated end point of clinical cure by day 7-8 was associated with more favorable hospital discharge dispositions, suggesting that clinical cure by day 7-8 may be a valid end point to use in adjudication protocols.

Simulation-based Mastery Learning Improves Critical Care Skills of Advanced Practice Providers.

Background: Advanced practice providers (APPs) are essential members of intensive care unit (ICU) interprofessional teams and are expected to be competent in performing procedures. There are no published criteria for establishing when APPs can independently perform procedures. Simulation-based mastery learning (SBML) is an effective strategy for improving critical care skills but has not been applied to practicing ICU APPs. Objective: The purpose of this study was to evaluate if an SBML curriculum could improve the critical care skills and procedural self-confidence of ICU APPs. Methods: We performed a pretest-posttest study of central venous catheter (CVC) insertion, thoracentesis, and mechanical ventilation (MV) management skills among ICU APPs who participated in an SBML course at an academic hospital. For each skill, APPs underwent baseline skills assessments (pretests) on a simulator using previously published checklists, followed by didactic sessions and deliberate practice with individualized feedback. Within 2 weeks, participants were required to meet or exceed previously established minimum passing standards (MPS) on simulated skills assessments (posttests) using the same checklists. Further deliberate practice was provided for those unable to meet the MPS until they retested and met this standard. We compared pretest to posttest skills checklist scores and procedural confidence. Results: All 12 eligible ICU APPs participated in internal jugular CVC, subclavian CVC, and MV training. Five APPs participated in thoracentesis training. At baseline, no APPs met the MPS on all skills. At training completion, all APPs achieved the mastery standard. Internal jugular CVC pretest performance improved from a mean of 67.2% (standard deviation [SD], 28.8%) items correct to 97.1% (SD, 3.8%) at posttest (P = 0.005). Subclavian CVC pretest performance improved from 29.2% (SD, 32.7%) items correct to 93.1% (SD 3.9%) at posttest (P < 0.001). Thoracentesis pretest skill improved from 63.9% (SD, 30.6%) items correct to 99.2% (SD, 1.7%) at posttest (P = 0.054). Pretest MV skills improved from 54.8% (SD, 19.7%) items correct to 92.3% (SD, 5.0%) at posttest (P < 0.001). APP procedural confidence improved for each skill from pre to posttest. Conclusion: SBML is effective for training APPs to perform ICU skills. Relying on traditional educational methods does not reliably ensure that APPs are adequately prepared to perform skills such as CVC insertion, thoracentesis, and MV management.

Machine learning links unresolving secondary pneumonia to mortality in patients with severe pneumonia, including COVID-19.

BACKGROUNDDespite guidelines promoting the prevention and aggressive treatment of ventilator-associated pneumonia (VAP), the importance of VAP as a driver of outcomes in mechanically ventilated patients, including patients with severe COVID-19, remains unclear. We aimed to determine the contribution of unsuccessful treatment of VAP to mortality for patients with severe pneumonia.METHODSWe performed a single-center, prospective cohort study of 585 mechanically ventilated patients with severe pneumonia and respiratory failure, 190 of whom had COVID-19, who underwent at least 1 bronchoalveolar lavage. A panel of intensive care unit (ICU) physicians adjudicated the pneumonia episodes and endpoints on the basis of clinical and microbiological data. Given the relatively long ICU length of stay (LOS) among patients with COVID-19, we developed a machine-learning approach called CarpeDiem, which grouped similar ICU patient-days into clinical states based on electronic health record data.RESULTSCarpeDiem revealed that the long ICU LOS among patients with COVID-19 was attributable to long stays in clinical states characterized primarily by respiratory failure. While VAP was not associated with mortality overall, the mortality rate was higher for patients with 1 episode of unsuccessfully treated VAP compared with those with successfully treated VAP (76.4% versus 17.6%, P < 0.001). For all patients, including those with COVID-19, CarpeDiem demonstrated that unresolving VAP was associated with a transitions to clinical states associated with higher mortality.CONCLUSIONSUnsuccessful treatment of VAP is associated with higher mortality. The relatively long LOS for patients with COVID-19 was primarily due to prolonged respiratory failure, placing them at higher risk of VAP.FUNDINGNational Institute of Allergy and Infectious Diseases (NIAID), NIH grant U19AI135964; National Heart, Lung, and Blood Institute (NHLBI), NIH grants R01HL147575, R01HL149883, R01HL153122, R01HL153312, R01HL154686, R01HL158139, P01HL071643, and P01HL154998; National Heart, Lung, and Blood Institute (NHLBI), NIH training grants T32HL076139 and F32HL162377; National Institute on Aging (NIA), NIH grants K99AG068544, R21AG075423, and P01AG049665; National Library of Medicine (NLM), NIH grant R01LM013337; National Center for Advancing Translational Sciences (NCATS), NIH grant U01TR003528; Veterans Affairs grant I01CX001777; Chicago Biomedical Consortium grant; Northwestern University Dixon Translational Science Award; Simpson Querrey Lung Institute for Translational Science (SQLIFTS); Canning Thoracic Institute of Northwestern Medicine.

Rats, Neuregulins and Radical Prostatectomy: A Conceptual Overview.

In the contemporary era of early detection, with mostly curative initial treatment for prostate cancer (PC), mortality rates have significantly diminished. In addition, mean age at initial PC diagnosis has decreased. Despite technical advancements, the probability of erectile function (EF) recovery post radical prostatectomy (RP) has not significantly changed throughout the last decade. Due to virtually unavoidable intraoperative cavernous nerve (CN) lesions and operations with younger patients, post-RP erectile dysfunction (ED) has now begun affecting these younger patients. To address this pervasive limitation, a plethora of CN lesion animal model investigations have analyzed the use of systemic/local treatments for EF recovery post-RP. Most promisingly, neuregulins (NRGs) have demonstrated neurotrophic effects in both neurodegenerative disease and peripheral nerve injury models. Recently, glial growth factor 2 (GGF2) has demonstrated far superior, dose-dependent, neuroprotective/restorative effects in the CN injury rat model, as compared to previous therapeutic counterparts. Although potentially impactful, these initial findings remain limited and under-investigated. In an effort to aid clinicians, our paper reviews post-RP ED pathogenesis and currently available therapeutic tools. To stimulate further experimentation, a standardized preparation protocol and in-depth analysis of applications for the CN injury rat model is provided. Lastly, we report on NRGs, such as GGF2, and their potentially revolutionary clinical applications, in hopes of identifying relevant future research directions.

The distribution of acquired peripheral nerve injuries associated with severe COVID-19 implicate a mechanism of entrapment neuropathy: a multicenter case series and clinical feasibility study of a wearable, wireless pressure sensor.

We diagnosed 66 peripheral nerve injuries in 34 patients who survived severe coronavirus disease 2019 (COVID-19). We combine this new data with published case series re-analyzed here (117 nerve injuries; 58 patients) to provide a comprehensive accounting of lesion sites. The most common are ulnar (25.1%), common fibular (15.8%), sciatic (13.1%), median (9.8%), brachial plexus (8.7%) and radial (8.2%) nerves at sites known to be vulnerable to mechanical loading. Protection of peripheral nerves should be prioritized in the care of COVID-19 patients. To this end, we report proof of concept data of the feasibility for a wearable, wireless pressure sensor to provide real time monitoring in the intensive care unit setting.

Diaphragm and Phrenic Nerve Ultrasound in COVID-19 Patients and Beyond: Imaging Technique, Findings, and Clinical Applications.

The diaphragm, the principle muscle of inspiration, is an under-recognized contributor to respiratory disease. Dysfunction of the diaphragm can occur secondary to lung disease, prolonged ventilation, phrenic nerve injury, neuromuscular disease, and central nervous system pathology. In light of the global pandemic of coronavirus disease 2019 (COVID-19), there has been growing interest in the utility of ultrasound for evaluation of respiratory symptoms including lung and diaphragm sonography. Diaphragm ultrasound can be utilized to diagnose diaphragm dysfunction, assess severity of dysfunction, and monitor disease progression. This article reviews diaphragm and phrenic nerve ultrasound and describes clinical applications in the context of COVID-19.

Outcomes after extracorporeal membrane oxygenation support in COVID-19 and non-COVID-19 patients.

BACKGROUND: Veno-venous extracorporeal membrane oxygenation (V-V ECMO) support is increasingly used in the management of COVID-19-related acute respiratory distress syndrome (ARDS). However, the clinical decision-making to initiate V-V ECMO for severe COVID-19 still remains unclear. In order to determine the optimal timing and patient selection, we investigated the outcomes of both COVID-19 and non-COVID-19 patients undergoing V-V ECMO support. METHODS: Overall, 138 patients were included in this study. Patients were stratified into two cohorts: those with COVID-19 and non-COVID-19 ARDS. RESULTS: The survival in patients with COVID-19 was statistically similar to non-COVID-19 patients (p = .16). However, the COVID-19 group demonstrated higher rates of bleeding (p = .03) and thrombotic complications (p < .001). The duration of V-V ECMO support was longer in COVID-19 patients compared to non-COVID-19 patients (29.0 ± 27.5 vs 15.9 ± 19.6 days, p < .01). Most notably, in contrast to the non-COVID-19 group, we found that COVID-19 patients who had been on a ventilator for longer than 7 days prior to ECMO had 100% mortality without a lung transplant. CONCLUSIONS: These findings suggest that COVID-19-associated ARDS was not associated with a higher post-ECMO mortality than non-COVID-19-associated ARDS patients, despite longer duration of extracorporeal support. Early initiation of V-V ECMO is important for improved ECMO outcomes in COVID-19 ARDS patients. Since late initiation of ECMO was associated with extremely high mortality related to lack of pulmonary recovery, it should be used judiciously or as a bridge to lung transplantation.

miR-221-5p-Mediated Downregulation of JNK2 Aggravates Acute Lung Injury.

Sepsis and acute lung injury (ALI) are linked to mitochondrial dysfunction; however, the underlying mechanism remains elusive. We previously reported that c-Jun N-terminal protein kinase 2 (JNK2) promotes stress-induced mitophagy by targeting small mitochondrial alternative reading frame (smARF) for ubiquitin-mediated proteasomal degradation, thereby preventing mitochondrial dysfunction and restraining inflammasome activation. Here we report that loss of JNK2 exacerbates lung inflammation and injury during sepsis and ALI in mice. JNK2 is downregulated in mice with endotoxic shock or ALI, concomitantly correlated inversely with disease severity. Small RNA sequencing revealed that miR-221-5p, which contains seed sequence matching to JNK2 mRNA 3' untranslated region (3'UTR), is upregulated in response to lipopolysaccharide, with dynamically inverse correlation with JNK2 mRNA levels. miR-221-5p targets the 3'UTR of JNK2 mRNA leading to its downregulation. Accordingly, miR-221-5p exacerbates lung inflammation and injury during sepsis in mice by targeting JNK2. Importantly, in patients with pneumonia in medical intensive care unit, JNK2 mRNA levels in alveolar macrophages flow sorted from non-bronchoscopic broncholaveolar lavage (BAL) fluid were inversely correlated strongly and significantly with the percentage of neutrophils, neutrophil and white blood cell counts in BAL fluid. Our data suggest that miR-221-5p targets JNK2 and thereby aggravates lung inflammation and injury during sepsis.

Prominent rash and multisystem inflammatory syndrome in a 29-year-old patient with COVID-19: a case report.

BACKGROUND: Adult patients with coronavirus disease present primarily with respiratory symptoms, but children and some adults may display a more systemic inflammatory syndrome with rash, fever, mucosal changes, and elevated inflammatory biomarkers. CASE PRESENTATION: Here, we report the case of a 29-year-old Hispanic patient presenting with significant rash and multisystem inflammation. We describe his clinical course, review dermatological manifestations of coronavirus disease, and summarize the pathophysiology of coronavirus disease-associated multisystem inflammation. CONCLUSION: This case should alert physicians to the atypical nature of presenting rash with minimal respiratory symptoms in coronavirus disease.

Diaphragm dysfunction in severe COVID-19 as determined by neuromuscular ultrasound.

Many survivors from severe coronavirus disease 2019 (COVID-19) suffer from persistent dyspnea and fatigue long after resolution of the active infection. In a cohort of 21 consecutive severe post-COVID-19 survivors admitted to an inpatient rehabilitation hospital, 16 (76%) of them had at least one sonographic abnormality of diaphragm muscle structure or function. This corresponded to a significant reduction in diaphragm muscle contractility as represented by thickening ratio (muscle thickness at maximal inspiration/end-expiration) for the post-COVID-19 compared to non-COVID-19 cohorts. These findings may shed new light on neuromuscular respiratory dysfunction as a contributor to prolonged functional impairments after hospitalization for post-COVID-19.

Improved Functional Outcome After Peripheral Nerve Stimulation of the Impaired Forelimb Post-stroke.

Lack of blood flow to the brain, i.e., ischemic stroke, results in loss of nerve cells and therefore loss of function in the effected brain regions. There is no effective treatment to improve lost function except restoring blood flow within the first several hours. Rehabilitation strategies are widely used with limited success. The purpose of this study was to examine the effect of electrical stimulation on the impaired upper extremity to improve functional recovery after stroke. We developed a rodent model using an electrode cuff implant onto a single peripheral nerve (median nerve) of the paretic forelimb and applied daily electrical stimulation. The skilled forelimb reaching test was used to evaluate functional outcome after stroke and electrical stimulation. Anterograde axonal tracing from layer V pyramidal neurons with biotinylated dextran amine was done to evaluate the formation of new neuronal connections from the contralesional cortex to the deafferented spinal cord. Rats receiving electrical stimulation on the median nerve showed significant improvement in the skilled forelimb reaching test in comparison with stroke only and stroke with sham stimulation. Rats that received electrical stimulation also exhibited significant improvement in the latency to initiate adhesive removal from the impaired forelimb, indicating better sensory recovery. Furthermore, axonal tracing analysis showed a significant higher midline fiber crossing index in the cervical spinal cord of rats receiving electrical stimulation. Our results indicate that direct peripheral nerve stimulation leads to improved sensorimotor recovery in the stroke-impaired forelimb, and may be a useful approach to improve post-stroke deficits in human patients.

Artificial Intelligence-Enabled POCUS in the COVID-19 ICU: A New Spin on Cardiac Ultrasound.

We present the novel use of a deep learning-derived technology trained on the skilled hand movements of cardiac sonographers that guides novice users to acquire high-quality bedside cardiac ultrasound images. We illustrate its use at the point of care through a series of patient encounters in the COVID-19 intensive care unit. (Level of Difficulty: Beginner.).

The lung microenvironment shapes a dysfunctional response of alveolar macrophages in aging.

Alveolar macrophages orchestrate the response to viral infections. Age-related changes in these cells may underlie the differential severity of pneumonia in older patients. We performed an integrated analysis of single-cell RNA-Seq data that revealed homogenous age-related changes in the alveolar macrophage transcriptome in humans and mice. Using genetic lineage tracing with sequential injury, heterochronic adoptive transfer, and parabiosis, we found that the lung microenvironment drove an age-related resistance of alveolar macrophages to proliferation that persisted during influenza A viral infection. Ligand-receptor pair analysis localized these changes to the extracellular matrix, where hyaluronan was increased in aged animals and altered the proliferative response of bone marrow-derived macrophages to granulocyte macrophage colony-stimulating factor (GM-CSF). Our findings suggest that strategies targeting the aging lung microenvironment will be necessary to restore alveolar macrophage function in aging.