A Care Step Pathway for the Diagnosis and Treatment of COVID-19-Associated Invasive Fungal Infections in the Intensive Care Unit.

BACKGROUND: In March 2020, the World Health Organization declared COVID-19, caused by the SARS-CoV-2 virus, a pandemic. Patients with severe cases resulting in hospitalization and mechanical ventilation are at risk for COVID-19-associated pulmonary aspergillosis, an invasive fungal infection, and should be screened for aspergillosis if they have persistent hemodynamic instability and fever. Early detection and treatment of this fungal infection can significantly reduce morbidity and mortality in this population. OBJECTIVE: To develop an evidence-based care step pathway tool to help intensive care unit clinicians assess, diagnose, and treat COVID-19-associated pulmonary aspergillosis. METHODS: A panel of 18 infectious disease experts, advanced practice registered nurses, pharmacists, and clinical researchers convened in a series of meetings to develop the Care Step Pathway tool, which was modeled on a tool developed by advanced practice nurses to evaluate and manage side effects of therapies for melanoma. The Care Step Pathway tool addresses various aspects of disease management, including assessment, screening, diagnosis, antifungal treatment, pharmacological considerations, and exclusion of other invasive fungal coinfections. RESULTS: The Care Step Pathway tool was applied in the care of a patient with COVID-19-associated aspergillosis. The patient was successfully treated. CONCLUSION: The Care Step Pathway is an effective educational tool to help intensive care unit clinicians consider fungal infection when caring for COVID-19 patients receiving mechanical ventilation in the intensive care unit, especially when the clinical course is deteriorating and antibiotics are ineffective.

Letter to the Editor: "Use of inhaled epoprostenol with high flow nasal oxygen in non-intubated patients with severe COVID-19".

PURPOSE: Acute lung injury associated with COVID-19 contributes significantly to its morbidity and mortality. Though invasive mechanical ventilation is sometimes necessary, the use of high flow nasal oxygen may avoid the need for mechanical ventilation in some patients. For patients approaching the limits of high flow nasal oxygen support, addition of inhaled pulmonary vasodilators is becoming more common but little is known about its effects. This is the first descriptive study of a cohort of patients receiving inhaled epoprostenol with high flow nasal oxygen for COVID-19. MATERIALS AND METHODS: We collected clinical data from the first fifty patients to receive inhaled epoprostenol while on high flow nasal oxygen at our institution. We compared the characteristics of patients who did and did not respond to epoprostenol addition. RESULTS: The 18 patients that did not stabilize or improve following initiation of inhaled epoprostenol had similar rates of invasive mechanical ventilation as those who improved or stabilized (50% vs 56%). Rates of mortality were not significantly different between the two groups (17% and 31%). CONCLUSIONS: In patients with COVID-19 induced hypoxemic respiratory failure, the use of inhaled epoprostenol with high flow nasal oxygen is feasible, but physiologic signs of response were not related to clinical outcomes.

Acute Respiratory Distress Syndrome in a Patient With Acute Promyelocytic Leukemia: Overlapping Between Differentiation Syndrome and COVID-19.

Differentiation syndrome (DS) is a relatively common and severe complication in acute promyelocytic leukemia (APL) patients undergoing induction therapy with all-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO). DS is a multisystem disorder with pulmonary involvement. The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is also a systemic disorder with similar pulmonary and other clinical manifestations as DS. Here, we report an APL case with overlapping between DS and COVID-19. After admission to the hospital, the patient was diagnosed with APL and underwent differentiation therapy with ATRA/ATO. In the meantime, COVID-19 was diagnosed with a positive polymerase chain reaction test of SARS-CoV-2 from an oropharyngeal swab. The patient developed acute respiratory distress syndrome, coagulopathy, and acute kidney injury, which fit the clinical pictures of both DS and COVID-19. The patient died at last and this complicate case imposed big challenges for clinicians due to the laboratory and imaging findings of DS disguised in the context of COVID-19. Therefore, comprehensive treatment strategy should be considered to balance the risk and benefit of differentiation therapy in the context of COVID-19.

What is the diagnostic accuracy of single nerve conduction studies and muscle ultrasound to identify critical illness polyneuromyopathy: a prospective cohort study.

BACKGROUND: Critical illness polyneuromyopathy (CIPNM) is a major cause of weakness in intensive care unit (ICU) patients, but current diagnostic tests are limited. We evaluated the generalizability and validity of single nerve conduction studies (NCS) and muscle ultrasound testing to identify CIPNM, and we also assessed the ability of muscle ultrasound to prognosticate patient outcomes. METHODS: This was a prospective cohort study of mechanically ventilated medical, cardiac, surgical, and neurosurgical ICU patients. We performed weekly strength testing, NCS, electromyography (EMG), and muscle ultrasound. We calculated the sensitivity, specificity, and other test characteristics of single NCS and muscle ultrasound, and we used multivariable regression models to assess the prognostic ability of muscle ultrasound. RESULTS: Ninety-five patients were enrolled. The incidence of probable CIPNM was 18% and did not differ significantly by type of ICU (p = 0.49). For diagnosing probable CIPNM, the peroneal motor NCS had a sensitivity of 94% (95% confidence interval (CI) 71-100%) and specificity of 91% (95% CI 82-96%), the sural sensory NCS had a sensitivity of 100% (95% CI 80-100%) and specificity of 42% (95% CI 31-54%), and abnormal muscle ultrasound echogenicity had a sensitivity of 82% (95% CI 48-98%) and specificity of 57% (95% CI 43-70%). Abnormal echogenicity was associated with reduced likelihood of discharge to home (9% vs 50%, p = 0.0001), fewer ICU-free days (median 3 (interquartile range 0-15) days vs 16 (9.3-19.3) days, p = 0.0002), and increased ICU mortality (42% vs 12%, p = 0.004). CONCLUSIONS: In a diverse cohort of critically ill patients, single NCS and muscle ultrasound achieved diagnostic accuracy for patients at risk for CIPNM. The routine utilization of these tests could be beneficial for all critically ill patients at risk for CIPNM.

Outcomes of ICU Patients With a Discharge Diagnosis of Critical Illness Polyneuromyopathy: A Propensity-Matched Analysis.

OBJECTIVES: To assess the impact of a discharge diagnosis of critical illness polyneuromyopathy on health-related outcomes in a large cohort of patients requiring ICU admission. DESIGN: Retrospective cohort with propensity score-matched analysis. SETTING: Analysis of a large multihospital database. PATIENTS: Adult ICU patients without preexisting neuromuscular abnormalities and a discharge diagnosis of critical illness polyneuropathy and/or myopathy along with adult ICU propensity-matched control patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 3,567 ICU patients with a discharge diagnosis of critical illness polyneuropathy and/or myopathy, we matched 3,436 of these patients to 3,436 ICU patients who did not have a discharge diagnosis of critical illness polyneuropathy and/or myopathy. After propensity matching and adjusting for unbalanced covariates, we used conditional logistic regression and a repeated measures model to compare patient outcomes. Compared to patients without a discharge diagnosis of critical illness polyneuropathy and/or myopathy, patients with a discharge diagnosis of critical illness polyneuropathy and/or myopathy had fewer 28-day hospital-free days (6 [0.1] vs 7.4 [0.1] d; p < 0.0001), had fewer 28-day ventilator-free days (15.7 [0.2] vs 17.5 [0.2] d; p < 0.0001), had higher hospitalization charges (313,508 [4,853] vs 256,288 [4,470] dollars; p < 0.0001), and were less likely to be discharged home (15.3% vs 32.8%; p < 0.0001) but had lower in-hospital mortality (13.7% vs 18.3%; p < 0.0001). CONCLUSIONS: In a propensity-matched analysis of a large national database, a discharge diagnosis of critical illness polyneuropathy and/or myopathy is strongly associated with deleterious outcomes including fewer hospital-free days, fewer ventilator-free days, higher hospital charges, and reduced discharge home but also an unexpectedly lower in-hospital mortality. This study demonstrates the clinical importance of a discharge diagnosis of critical illness polyneuropathy and/or myopathy and the need for effective preventive interventions.

Euglycemic Diabetic Ketoacidosis With Prolonged Glucosuria Associated With the Sodium-Glucose Cotransporter-2 Canagliflozin.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors improve glycemic control by a reversible inhibition of the sodium-glucose cotransporters in the renal proximal tubules resulting in increased urinary glucose. This unique mechanism, independent of insulin secretion and beta cell function, has made this class of medication desirable in patients with type 2 diabetes. However in May 2015, the US Food and Drug Administration issued a safety warning pertaining to the development of diabetic ketoacidosis (DKA) with the use of SGLT2 inhibitors. DKA associated with SGLT2 inhibitors frequently develops in the absence of hyperglycemia, which makes the diagnosis more challenging. Due to the reversible inhibition of SGLT2 by this class of medication, a quick recovery of glucosuria after cessation of medication is expected. In this article, we present a case of a 50-year-old woman with type 2 diabetes who developed euglycemic DKA after initiating therapy with canagliflozin. This case of DKA associated with SGLT2 inhibitor use was unique due to her hypoglycemic presentation and persistent glucosuria. SGLT2 inhibitors such as canagliflozin may predispose patients not only to diabetic ketoacidosis but also to prolonged glucosuria.

Prototype electronic stethoscope vs. conventional stethoscope for auscultation of heart sounds.

In an effort to decrease the spread of hospital-acquired infections, many hospitals currently use disposable plastic stethoscopes in patient rooms. As an alternative, this study examines a prototype electronic stethoscope that does not break the isolation barrier between clinician and patient and may also improve the diagnostic accuracy of the stethoscope exam. This study aimed to investigate whether the new prototype electronic stethoscope improved auscultation of heart sounds compared to the standard conventional isolation stethoscope. In a controlled, non-blinded, cross-over study, clinicians were randomized to identify heart sounds with both the prototype electronic stethoscope and a conventional stethoscope. The primary outcome was the score on a 10-question heart sound identification test. In total, 41 clinicians completed the study. Subjects performed significantly better in the identification of heart sounds when using the prototype electronic stethoscope (median = 9 [7-10] vs. 8 [6-9] points, p value <0.0001). Subjects also significantly preferred the prototype electronic stethoscope. Clinicians using a new prototype electronic stethoscope achieved greater accuracy in identification of heart sounds and also universally favoured the new device, compared to the conventional stethoscope.

Faculty staff-guided versus self-guided ultrasound training for internal medicine residents.

OBJECTIVES: Ultrasonography is of growing importance within internal medicine (IM), but the optimal method of training doctors to use it is uncertain. In this study, the authors provide the first objective comparison of two approaches to training IM residents in ultrasonography. METHODS: In this randomised trial, a simulation-based ultrasound training curriculum was implemented during IM intern orientation at a tertiary care teaching hospital. All 72 incoming interns attended a lecture and were given access to online modules. Interns were then randomly assigned to a 4-hour faculty-guided (FG) or self-guided (SG) ultrasound training session in a simulation laboratory with both human and manikin models. Interns were asked to self-assess their competence in ultrasonography and underwent an objective structured clinical examination (OSCE) to assess their competence in basic and procedurally oriented ultrasound tasks. The primary outcome was the score on the OSCE. RESULTS: Faculty-guided training was superior to self-guided training based on the OSCE scores. Subjects in the FG training group achieved significantly higher OSCE scores on the two subsets of task completion (0.9-point difference, 95% confidence interval [CI] 0.27-1.54; p = 0.008) and ultrasound image quality (2.43-point difference, 95% CI 1.5-3.36; p < 0.001). Both training groups demonstrated an increase in self-assessed competence after their respective training sessions and there was little difference between the groups. Subjects rated the FG training group much more favourably than the SG training group. CONCLUSIONS: Both FG and SG ultrasound training curricula can improve the self-reported competence of IM interns in ultrasonography. However, FG training was superior to SG training in both skills acquisition and intern preference. Incorporating mandatory ultrasound training into IM residencies can address the perceived need for ultrasound training, improve confidence and procedural skills, and may enhance patient safety. However, the optimal training method may require significant faculty input.

The effect of omalizumab on ventilation and perfusion in adults with allergic asthma.

Omalizumab promotes clinical improvement in patients with allergic asthma, but its effect on pulmonary function is unclear. One possibility is that omalizumab improves asthma symptoms through effects on the regional distributions of ventilation, perfusion, and ventilation/perfusion matching, metrics which can be assessed with Nitrogen-13-saline Position Emission Tomography (PET). Four adults with moderate to severe uncontrolled allergic asthma underwent symptom assessment, spirometry and functional pulmonary imaging with Nitrogen-13-saline PET before and after 4-5 months of treatment with omalizumab. PET imaging was used to determine ventilation/perfusion ratios, the heterogeneity (coefficient of variation, COV) of ventilation and perfusion, and lung regions with ventilation defects. There were no significant changes in spirometry values after omalizumab treatment, but there was a trend towards an improvement in symptom scores. There was little change in the matching of ventilation and perfusion. The COV of perfusion was similar before and after omalizumab treatment. The COV of ventilation was also similar before (0.57 (0.28)) and after (0.66 (0.13)) treatment, and it was similar to previously published values for healthy subjects. There was a non-significant trend towards an increase in the extent of ventilation defects after omalizumab treatment, from 5 (15)% to 12.8 (14.7)%. Treatment of moderate to severe uncontrolled allergic asthma with omalizumab did not result in a significant improvement in ventilation and perfusion metrics assessed with functional PET imaging. The normal COV of ventilation which was unaffected by treatment supports the hypothesis that omalizumab exerts its clinical effect on lung function during allergen exposure rather than in between exacerbations.