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.

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.

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.

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.

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.

Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia.

Some patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop severe pneumonia and acute respiratory distress syndrome1 (ARDS). Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus differs from that in other types of pneumonia2. Here we investigate SARS-CoV-2 pathobiology by characterizing the immune response in the alveoli of patients infected with the virus. We collected bronchoalveolar lavage fluid samples from 88 patients with SARS-CoV-2-induced respiratory failure and 211 patients with known or suspected pneumonia from other pathogens, and analysed them using flow cytometry and bulk transcriptomic profiling. We performed single-cell RNA sequencing on 10 bronchoalveolar lavage fluid samples collected from patients with severe coronavirus disease 2019 (COVID-19) within 48 h of intubation. In the majority of patients with SARS-CoV-2 infection, the alveolar space was persistently enriched in T cells and monocytes. Bulk and single-cell transcriptomic profiling suggested that SARS-CoV-2 infects alveolar macrophages, which in turn respond by producing T cell chemoattractants. These T cells produce interferon-γ to induce inflammatory cytokine release from alveolar macrophages and further promote T cell activation. Collectively, our results suggest that SARS-CoV-2 causes a slowly unfolding, spatially limited alveolitis in which alveolar macrophages containing SARS-CoV-2 and T cells form a positive feedback loop that drives persistent alveolar inflammation.

Imaging Review of Peripheral Nerve Injuries in Patients with COVID-19.

With surging numbers of patients with coronavirus disease 2019 (COVID-19) throughout the world, neuromuscular complications and rehabilitation concerns are becoming more apparent. Peripheral nerve injury can occur in patients with COVID-19 secondary to postinfectious inflammatory neuropathy, prone positioning-related stretch and/or compression injury, systemic neuropathy, or nerve entrapment from hematoma. Imaging of peripheral nerves in patients with COVID-19 may help to characterize nerve abnormality, to identify site and severity of nerve damage, and to potentially elucidate mechanisms of injury, thereby aiding the medical diagnosis and decision-making process. This review article aims to provide a first comprehensive summary of the current knowledge of COVID-19 and peripheral nerve imaging.

Bronchoscopy on Intubated COVID-19 Patients is Associated with Low Infectious Risk to Operators at a High-Volume Center Using an Aerosol-minimizing Protocol.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic raised concern for exposure to healthcare providers through aerosol generating procedures, such as bronchoalveolar lavage (BAL). Current society guidelines recommended limiting use of BAL to reduce operators' risk for infection, yet data on the infection rate for providers after BAL is sparse. Since March 2020, our institution used a modified protocol to perform over 450 BALs on intubated COVID-19 patients. We therefore sought to describe the subsequent infectious risks to providers associated with BAL. METHODS: Fifty-two pulmonary and critical care providers (faculty and fellows) at our tertiary-care, urban medical center were surveyed. Survey participants were asked to provide the number of BALs on COVID-19 patients they performed, the number of weeks they cared for intensive care unit (ICU) patients with COVID-19, and the results of any SARS-CoV-2 testing that they received. Participants were asked to assess the difficulty of BAL on intubated COVID-19 patients as compared to routine ICU BAL using a numeric perceived difficulty score ranging from 1 (easier) to 10 (harder). RESULTS: We received forty-seven responses from fifty-two surveyed (90% response rate), with 2 declining to participate. Many respondents (19/45, 42%) spent >5 weeks on an ICU service with COVID-19 patients. The number of BALs performed by providers ranged from 0 to >60. Sixteen of the 35 providers (46%) who performed BALs underwent at least one nasopharyngeal (NP) swab to test for SARS-CoV-2, but none were positive. Twenty-seven of the 35 providers (77%) who performed BALs underwent SARS-CoV-2 serology testing, and only one (3.7%) was positive. Respondents indicated occasionally not being able to follow aerosol-minimizing steps but overall felt BALs in COVID-19 patients was only slightly more difficult than routine ICU BAL. DISCUSSION: At a high-volume center having performed >450 BALs on intubated COVID-19 patients with aerosol-limiting precautions, our survey of bronchoscopists found no positive NP SARS-CoV-2 tests and only one positive antibody test result. While the optimal role for COVID-19 BAL remains to be determined, these data suggest that BAL can be safely performed in intubated COVID-19 patients if experienced providers take precautions to limit aerosol generation and wear personal protective equipment.