Pleural Uptake Patterns in F18Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) Scans Improve the Identification of Malignant Pleural Effusions.

BACKGROUND: The confirmation of malignant pleural effusions (MPE) requires an invasive procedure. Diagnosis can be difficult and may require repeated thoracentesis or biopsies. F18Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) can characterize the extent of malignant involvement in areas of increased uptake. Patterns of uptake in the pleura may be sufficient to obviate the need for further invasive procedures. METHODS: This is a retrospective review of patients with confirmed malignancy and suspected MPE. Patients who underwent diagnostic thoracentesis with cytology and contemporaneous FDG-PET were identified for analysis. Some underwent confirmatory pleural biopsy. The uptake pattern on FDG-PET underwent blinded review and was categorized based on the pattern of uptake. RESULTS: One hundred consecutive patients with confirmed malignancy, suspected MPE and corresponding FDG-PET scans were reviewed. MPE was confirmed in 70 patients with positive pleural fluid cytology or tissue pathology. Of the remaining patients, 15 had negative cytopathology, 14 had atypical cells and 1 had reactive cells. Positive uptake on FDG-PET was noted in 76 patients. The concordance of malignant histology and positive FDG-PET occurred in 58 of 76 patients (76%). Combining histologically confirmed MPE with atypical cytology, positive pleural FDG-PET uptake had a positive predictive value of 91% for MPE. An encasement pattern had a 100% PPV for malignancy. CONCLUSION: Positive FDG-PET pleural uptake represents an excellent method to identify MPE, especially in patients with an encasement pattern. This may eliminate the need for additional invasive procedures in some patients, even when initial pleural cytology is negative.

Percutaneous Tracheostomy in Respiratory Failure Due to COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can lead to hypoxemic respiratory failure resulting in prolonged mechanical ventilation. Typically, tracheostomy is considered in patients who remain ventilator dependent beyond 2 weeks. However, in the setting of this novel respiratory virus, the safety and benefits of tracheostomy are not well-defined. Our aim is to describe our experience with percutaneous tracheostomy in patients with COVID-19. MATERIALS AND METHODS: This is a single center retrospective descriptive study. We reviewed comorbidities and outcomes in patients with respiratory failure due to COVID-19 who underwent percutaneous tracheostomy at our institution from April 2020 to September 2020. In addition, we provide details of our attempt to minimize aerosolization by using a modified protocol with brief periods of planned apnea. RESULTS: A total of 24 patients underwent percutaneous tracheostomy during the study. The average body mass index was 33.0±10.0. At 30 days posttracheostomy 17 (71%) patients still had the tracheostomy tube and 14 (58%) remained ventilator dependent. There were 3 (13%) who died within 30 days. At the time of data analysis in November 2020, 9 (38%) patients had died and 7 (29%) had been decannulated. None of the providers who participated in the procedure experienced signs or symptoms of COVID-19 infection. CONCLUSION: Percutaneous tracheostomy in prolonged respiratory failure due to COVID-19 appears to be safe to perform at the bedside for both the patient and health care providers in the appropriate clinical context. Morbid obesity did not limit the ability to perform percutaneous tracheostomy in COVID-19 patients.

Validation of an acoustic gastrointestinal surveillance biosensor for postoperative ileus.

BACKGROUND: Postoperative ileus (POI) can worsen outcomes, increase cost, and prolong hospitalization. An objective marker could help identify POI patients who should not be prematurely fed. We developed a disposable, non-invasive acoustic gastro-intestinal surveillance (AGIS) biosensor. We tested whether AGIS can distinguish healthy controls from patients recovering from abdominal surgery. STUDY DESIGN: AGIS is a disposable plastic device embedded with a microphone that adheres to the abdominal wall and connects to a computer that measures acoustic event rates. We compared intestinal rates of healthy subjects using AGIS for 60 min after a standardized meal to recordings of two postoperative groups: (1) patients tolerating standardized feeding and (2) POI patients. We compared intestinal rates among groups using ANOVA and t tests. RESULTS: There were 8 healthy controls, 7 patients tolerating feeding, and 25 with POI; mean intestinal rates were 0.14, 0.03, and 0.016 events per second, respectively (ANOVA p < 0.001). AGIS separated patients from controls with 100 % sensitivity and 97 % specificity. Among patients, rates were higher in fed versus POI subjects (p = 0.017). CONCLUSION: Non-invasive, abdominal acoustic monitoring distinguishes POI from non-POI subjects. Future research will test whether AGIS can identify patients at risk for development of POI and assist with postoperative feeding decisions.

Aldosterone deficiency and mineralocorticoid receptor antagonism prevent angiotensin II-induced cardiac, renal, and vascular injury.

Angiotensin II causes cardiovascular injury in part by aldosterone-induced mineralocorticoid receptor activation, and it can also activate the mineralocorticoid receptor in the absence of aldosterone in vitro. Here we tested whether endogenous aldosterone contributes to angiotensin II/salt-induced cardiac, vascular, and renal injury by the mineralocorticoid receptor. Aldosterone synthase knockout mice and wild-type littermates were treated with angiotensin II or vehicle plus the mineralocorticoid receptor antagonist spironolactone or regular diet while drinking 0.9% saline. Angiotensin II/salt caused hypertension in both the knockout and wild-type mice, an effect significantly blunted in the knockout mice. Either genetic aldosterone deficiency or mineralocorticoid receptor antagonism reduced cardiac hypertrophy, aortic remodeling, and albuminuria, as well as cardiac, aortic, and renal plasminogen activator inhibitor-1 mRNA expression during angiotensin II treatment. Mineralocorticoid receptor antagonism reduced angiotensin II/salt-induced glomerular hypertrophy, but aldosterone deficiency did not. Combined mineralocorticoid receptor antagonism and aldosterone deficiency reduced blood urea nitrogen and restored nephrin immunoreactivity. Angiotensin II/salt also promoted glomerular injury through the mineralocorticoid receptor in the absence of aldosterone. Thus, mineralocorticoid antagonism may have protective effects in the kidney beyond aldosterone synthase inhibition.

Context mediates antimicrobial efficacy of kinocidin congener peptide RP-1.

Structure-mechanism relationships are key determinants of host defense peptide efficacy. These relationships are influenced by anatomic, physiologic and microbiologic contexts. Structure-mechanism correlates were assessed for the synthetic peptide RP-1, modeled on microbicidal domains of platelet kinocidins. Antimicrobial efficacies and mechanisms of action against susceptible ((S)) or resistant ((R)) Salmonella typhimurium (ST), Staphylococcus aureus (SA), and Candida albicans (CA) strain pairs were studied at pH 7.5 and 5.5. Although RP-1 was active against all study organisms, it exhibited greater efficacy against bacteria at pH 7.5, but greater efficacy against CA at pH 5.5. RP-1 de-energized SA and CA, but caused hyperpolarization of ST in both pH conditions. However, RP-1 permeabilized ST(S) and CA strains at both pH, whereas permeabilization was modest for ST(R) or SA strain at either pH. Biochemical analysis, molecular modeling, and FTIR spectroscopy data revealed that RP-1 has indistinguishable net charge and backbone trajectories at pH 5.5 and 7.5. Yet, concordant with organism-specific efficacy, surface plasmon resonance, and FTIR, molecular dynamics revealed modest helical order increases but greater RP-1 avidity and penetration of bacterial than eukaryotic lipid systems, particularly at pH 7.5. The present findings suggest that pH- and target-cell lipid contexts influence selective antimicrobial efficacy and mechanisms of RP-1 action. These findings offer new insights into selective antimicrobial efficacy and context-specificity of antimicrobial peptides in host defense, and support design strategies for potent anti-infective peptides with minimal concomitant cytotoxicity.

Structured interdisciplinary rounds in a medical teaching unit: improving patient safety.

BACKGROUND: Effective collaboration and teamwork is essential to providing safe hospital care. The objective of this study was to assess the effect of an intervention designed to improve interdisciplinary collaboration and lower the rate of adverse events (AEs). METHODS: The study was a controlled trial of an intervention, Structured Inter-Disciplinary Rounds, implemented in 1 of 2 similar medical teaching units in a tertiary care academic hospital. The intervention combined a structured format for communication with a forum for regular interdisciplinary meetings. We conducted a retrospective medical record review evaluating 370 randomly selected patients admitted to the intervention and control units (n = 185 each) in the 24 weeks after and 185 admitted to the intervention unit in the 24 weeks before the implementation of Structured Inter-Disciplinary Rounds (N = 555). Medical records were screened for AEs. Two hospitalists confirmed the presence of AEs and assessed their preventability and severity in a masked fashion. We used multivariable Poisson regression models to compare the adjusted incidence of AEs in the intervention unit to that in concurrent and historic control units. RESULTS: The rate of AEs was 3.9 per 100 patient-days for the intervention unit compared with 7.2 and 7.7 per 100 patient-days, respectively, for the concurrent and historic control units (adjusted rate ratio, 0.54; P = .005; and 0.51; P = .001). The rate of preventable AEs was 0.9 per 100 patient-days for the intervention unit compared with 2.8 and 2.1 per 100 patient-days for the concurrent and historic control units (adjusted rate ratio, 0.27; P = .002; and 0.37; P = .02). The low number of AEs rated as serious or life-threatening precluded statistical analysis for differences in rates of events classified as serious or serious and preventable. CONCLUSION: Structured Inter-Disciplinary Rounds significantly reduced the adjusted rate of AEs in a medical teaching unit.

Dynamics of intrapulmonary bacterial growth in a murine model of repeated microaspiration.

To study the change in intrapulmonary bacterial growth rate over time during Gram-negative pneumonia, a two-hit model of recurrent bacterial aspiration was developed in mice. A mutant of Klebsiella pneumoniae was isolated that could be distinguished from the wild type when cultured on appropriate media. These strains were intranasally administered, 4 h apart, to mice whose lungs were quantitatively cultured 24 h later. The relative burden of each aspirated inoculum was determined, and, using the administered dose and the number of bacteria from each inoculum present at the end of the experiment, first-order growth constants for each inoculum were calculated. Results indicate that after an initial aspiration of this organism, subsequently aspirated bacteria proliferate more slowly. When two aspirations occurred 4 h apart, the bacteria aspirated first represented 96% of total lung burden at 24 h. The growth constant of the second inoculum was related to the magnitude of the first inoculum in an inverse, nonlinear fashion. When parallel experiments were performed in complement C3-deficient mice, no suppression of the second inoculum was noted, suggesting that early upregulation of antibacterial activity in the lung is a C3-mediated event.