Effects of corticosteroids in hospitalized patients with Legionella pneumonia: A retrospective cohort study.

INTRODUCTION: Legionella pneumophila is an important cause of pneumonia, however there is scant literature assessing the therapeutic benefit of corticosteroids in treatment. We sought to investigate the association between corticosteroid use and in-hospital mortality for patients hospitalized with Legionella pneumonia. METHODS: Data was collected retrospectively from January 2012 to July 2019 at a 705 bed hospital in New York City. Patients were included if they received a positive Legionella test. Exclusion criteria included age <18, concurrent immunosuppression, and HIV diagnosis. We assessed the relationship between corticosteroid use and in-hospital mortality. Statistical analyses were performed in RStudio. RESULTS: The study included 160 patients, among which 32 (20%) received steroids. Overall mortality was 7.5% (12.5% among steroid recipients, 6.2% among controls). 25% of patients were admitted to the ICU (37.5% among steroid recipients, 21.9% among controls). Adjusted analysis showed steroid recipients did not have significantly different mortality (aOR = 2.56, p = 0.436). Steroid use was not significantly associated with longer LOS (p = 0.22). Steroid use was significantly associated with hyperglycemia (aOR = 2.91, p = 0.018) and GI bleed (OR = 9.0, p = 0.014). CONCLUSIONS: We found that in patients hospitalized with Legionella pneumonia, corticosteroid administration was not significantly associated with longer hospitalization or mortality. All findings held true when adjusting for known predictors of pneumonia severity. Corticosteroid use was associated with increased rates of hyperglycemia and GIB requiring blood transfusion. The results of this study are consistent with guidelines recommending against routine use of corticosteroids in CAP.

Inhaled pulmonary vasodilators are not associated with improved gas exchange in mechanically ventilated patients with COVID-19: A retrospective cohort study.

PURPOSE: Measure the effect of inhaled pulmonary vasodilators on gas exchange in mechanically ventilated patients with COVID-19. METHODS: A retrospective observational cohort study at three New York University Hospitals was performed including eighty-four mechanically ventilated SARS Cov-2 nasopharyngeal PCR positive patients, sixty nine treated with inhaled nitric oxide (iNO) and fifteen with inhaled epoprostenol (iEPO). The primary outcomes were change in PAO2:FIO2 ratio, oxygenation Index (OI), and ventilatory ratio (VR) after initiation of inhaled pulmonary vasodilators. RESULTS: There was no significant change in PAO2:FIO2ratio after initiation of iNO (mean - 4.1, 95% CI -17.3-9.0, P = 0.54) or iEPO (mean - 3.4, 95% CI -19.7-12.9, P = 0.66), in OI after initiation of iNO (mean 2.1, 95% CI-0.04-4.2, P = 0.054) or iEPO (mean - 3.4, 95% CI -19.7-12.9, P = 0.75), or in VR after initiation of iNO (mean 0.17, 95% CI -0.03-0.36, P = 0.25) or iEPO (mean 0.33, 95% CI -0.0847-0.74, P = 0.11). PAO2:FIO2, OI and VR did not significantly change over a five day period starting the day prior to drug initiation in patients who received either iNO or iEPO assessed with a fixed effects model. CONCLUSION: Inhaled pulmonary vasodilators were not associated with significant improvement in gas exchange in mechanically ventilated patients with COVID-19.

Spatial frequency-dependent pulse-height spectrum and method for analyzing detector DQE(f) from ensembles of single X-ray images.

PURPOSE: Scintillators and photoconductors used in energy integrating detectors (EIDs) have inherent variations in their imaging response to single-detected X-rays due to variations in X-ray energy deposition and secondary quanta generation and transport, which degrades DQE(f). The imaging response of X-ray scintillators to single X-rays may be recorded and studied using single X-ray imaging (SXI) experiments; however, no method currently exists for relating SXI experimental results to EID DQE(f). This work proposes a general analytical framework for computing and analyzing the DQE(f) performance of EIDs from single X-ray image ensembles using a spatial frequency-dependent pulse-height spectrum. METHODS: A spatial frequency (f)-dependent gain, g ∼ ( f ) $\tilde{g}(f)$ , is defined as the Fourier transform of the imaging response of an EID to a single-detected X-ray. A f-dependent pulse-height spectrum, Pr [ g ∼ ( f ) ] $\Pr [\tilde{g}(f)]$ , is defined as the 2D probability density function of g ∼ ( f ) $\tilde{g}(f)$ over the complex plane. Pr [ g ∼ ( f ) ] $\Pr [\tilde{g}(f)]$ is used to define a f-dependent Swank factor, AS (f), which fully characterizes the DQE(f) degradation due to single X-ray noise. AS (f) is analyzed in terms of its degradation due to Swank noise, variations in the frequency-dependent attenuation of | g ∼ ( f ) | $| {\tilde{g}(f)} |$ , and noise in arg g ∼ ( f ) $\arg \tilde{g}(f)$ which occurs due to variations in the asymmetry in each single X-ray's imaging response. Three example imaging systems are simulated to demonstrate the impact of depth-dependent variation in g ∼ ( f ) $\tilde{g}(f)$ , remote energy deposition, and a finite number of secondary quanta, on Pr [ g ∼ ( f ) ] $\Pr [\tilde{g}(f)]$ , AS (f), MTF(f), and NPS(f)/NPS(0), which are computed from ensembles of single X-ray images. The same is also demonstrated by simulating a realistic imaging system; that is, a Gd2 O2 S-based EID. Using the latter imaging system, the convergence of AS (f) estimates is investigated as a function of the number of detected X-rays per ensemble. RESULTS: Depth-dependent g ∼ ( f ) $\tilde{g}(f)$ variation resulted in AS (f) degradation exclusively due to depth-dependent optical Swank noise and the Lubberts effect. Conversely, the majority of AS (f) degradation caused by remote energy deposition and finite secondary quanta occurred due to variations in arg g ∼ ( f ) $\arg \tilde{g}(f)$ . When using input X-ray energies below the K-edge of Gd, variations in the frequency-dependent attenuation of | g ∼ ( f ) | $| {\tilde{g}(f)} |$ accounted for the majority of AS (f) degradation in the GOS-based EID, and very little Swank noise and variations in arg g ∼ ( f ) $\arg \tilde{g}(f)$ were observed. Above the K-edge, however, AS (f) degradation due to Swank noise and variations in arg g ∼ ( f ) $\arg \tilde{g}(f)$ greatly increased. The convergence of AS (f) was limited by variation in arg g ∼ ( f ) $\arg \tilde{g}(f)$ ; imaging systems with more variation in arg g ∼ ( f ) $\arg \tilde{g}(f)$ required more detected X-rays per ensemble. CONCLUSIONS: An analytical framework is proposed that generalizes the pulse-height spectrum and Swank factor to arbitrary f. The impact of single X-ray noise sources, such as the Lubberts effect, remote energy deposition, and finite secondary quanta on detector performance, may be represented using Pr [ g ∼ ( f ) ] $\Pr [\tilde{g}(f)]$ , and quantified using AS (f). The approach may be used to compute MTF(f), NPS(f), and DQE(f) from ensembles of single X-ray images and provides an additional tool to analyze proposed EID designs.

Microbial signatures in the lower airways of mechanically ventilated COVID-19 patients associated with poor clinical outcome.

Respiratory failure is associated with increased mortality in COVID-19 patients. There are no validated lower airway biomarkers to predict clinical outcome. We investigated whether bacterial respiratory infections were associated with poor clinical outcome of COVID-19 in a prospective, observational cohort of 589 critically ill adults, all of whom required mechanical ventilation. For a subset of 142 patients who underwent bronchoscopy, we quantified SARS-CoV-2 viral load, analysed the lower respiratory tract microbiome using metagenomics and metatranscriptomics and profiled the host immune response. Acquisition of a hospital-acquired respiratory pathogen was not associated with fatal outcome. Poor clinical outcome was associated with lower airway enrichment with an oral commensal (Mycoplasma salivarium). Increased SARS-CoV-2 abundance, low anti-SARS-CoV-2 antibody response and a distinct host transcriptome profile of the lower airways were most predictive of mortality. Our data provide evidence that secondary respiratory infections do not drive mortality in COVID-19 and clinical management strategies should prioritize reducing viral replication and maximizing host responses to SARS-CoV-2.

Use of a Multidisciplinary Mechanical Ventilation Weaning Protocol to Improve Patient Outcomes and Empower Staff in a Medical Intensive Care Unit.

BACKGROUND: Prolonged duration of mechanical ventilation is associated with higher mortality and increased patient complications; conventional physician-directed weaning methods are highly variable and permit significant time that weaning is inefficient and ineffective. OBJECTIVES: The primary objective of this quality improvement project was to implement a registered nurse (RN)- and respiratory therapist (RT)-driven mechanical ventilation weaning protocol in a medical intensive care unit (ICU) at a tertiary care academic medical center. METHODS: This quality improvement project used a quasi-experimental design with a retrospective usual care group who underwent physician-directed (conventional) weaning (n = 51) and a prospective intervention group who underwent protocol-directed weaning (n = 54). Outcomes included duration of mechanical ventilation, ICU length of stay, reintubation rates, and RN and RT satisfaction with the weaning protocol. RESULTS: Patients in the RN- and RT-driven mechanical ventilation weaning protocol group had significantly lower duration of mechanical ventilation (74 vs 152 hours; P = .002) and ICU length of stay (6.7 vs 10.2 days; P = .031). There was no significant difference in reintubation rates between groups. Staff surveys indicate that both RN and RTs were satisfied with the process change. DISCUSSION: Implementation of a multidisciplinary mechanical ventilation weaning protocol is a safe and effective way to improve patient outcomes and empower ICU staff.

Microbial signatures in the lower airways of mechanically ventilated COVID19 patients associated with poor clinical outcome.

Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal ( Mycoplasma salivarium ), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized.

Microbial signatures in the lower airways of mechanically ventilated COVID19 patients associated with poor clinical outcome.

Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal ( Mycoplasma salivarium ), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized.

Uninterrupted Continuous and Intermittent Nebulizer Therapy in a COVID-19 Patient Using Sequential Vibratory Mesh Nebulizers: A Case Report.

Interruptions in continuous nebulized pulmonary vasodilators, such as epoprostenol, can potentially result in clinical deterioration in respiratory status. Coadministration of other intermittent nebulized therapies may require opening the ventilator circuit to facilitate administration. However, in patients with SARS-CoV2 infection, it is preferred to avoid opening the circuit whenever feasible to prevent aerosolization of the virus and exposure of health care workers. In this study, we describe a unique method of administering continuous epoprostenol nebulization and intermittent nebulized antibiotics, mucolytics, and bronchodilators, using Aerogen vibrating mesh nebulizers without interruptions in epoprostenol or opening the ventilator circuit. This technique set up consisted of stacking two Aerogen nebulizer cups, each with its own controller. This approach was successful in allowing concomitant delivery of intermittent and continuous nebulized therapy without interruptions. To our knowledge, this method has not been previously described in the literature and may be helpful to bedside clinicians facing a similar clinical scenario.

Evaluation of a hybrid direct-indirect active matrix flat-panel imager using Monte Carlo simulation.

Purpose: Monte Carlo simulations were used to evaluate the imaging properties of a composite direct-indirect active matrix flat-panel imager (AMFPI) with potentially more favorable tradeoffs between x-ray quantum efficiency and spatial resolution than direct or indirect AMFPIs alone. This configuration, referred to as a hybrid AMFPI, comprises a scintillator that is optically coupled to an a-Se direct AMFPI through a transparent electrode and hole blocking layer, such that a-Se acts as both a direct x-ray converter and an optical sensor. Approach: GEANT4 was used to simulate x-ray energy deposition, optical transport, and charge signal generation processes in various hybrid AMPFI configurations under RQA5 and RQA9 x-ray beam conditions. The Fujita-Lubberts-Swank method was used to quantify the impact of irradiation geometry, x-ray converter thicknesses, conversion gain of each layer, and x-ray cross talk between layers on detective quantum efficiency (DQE). Results: Each hybrid configuration had a greater DQE than its direct AMFPI layer alone. The DQE improvement was largest at low spatial frequencies in both front- and back-irradiation (BI) geometries due to increased x-ray quantum efficiency provided by the scintillator. DQE improvements persisted at higher frequencies in BI geometry due to preferential x-ray absorption in a-Se. Matching the x-ray-to-charge conversion gains of a hybrid AMFPI's direct and indirect detection layers affects its Swank factor and, thus, DQE(0). X-ray cross talk has a negligible impact on the DQE ( f ) of hybrid AMFPIs with sufficiently high optical quantum efficiency. Conclusion: An optimized hybrid AMFPI can achieve greater DQE performance than current direct or indirect AMFPIs.

Erratum: Back-irradiated and dual-screen sandwich detector configurations for radiography (Erratum).

[This corrects the article DOI: 10.1117/1.JMI.6.3.033501.].

Back-irradiated and dual-screen sandwich detector configurations for radiography.

Recent advances in thin film transistor array technology have enabled the possibility of "back-irradiated" (BI) indirect active-matrix flat-panel imagers (AMFPIs), in which x-rays first expose the scintillator through the optical sensor, and "dual-screen" AMFPIs, in which two scintillating screens are sandwiched around a bidirectional active matrix. We developed a theoretical treatment of such detectors. The theory is used to investigate possible imaging performance improvements over conventional "front-irradiation" (FI) AMFPIs, where the active matrix is opposite the x-ray entrance surface. Simple expressions for the modulation transfer function, normalized noise power spectrum, Swank factor ( A s ), Lubberts function L ( f ) , and spatial frequency-dependent detective quantum efficiency DQE ( f ) are derived and used to compute these quantities for a variety of FI, BI, and dual-screen detector configurations. DQE ( f ) is used as the figure of merit for optimizing and comparing the performance of the various configurations. Large performance improvements over FI single-screen systems are found possible with BI. Further improvements are found possible with dual-screen configurations. The ratio of the thicknesses of the two screens that optimizes DQE is generally asymmetric, with the thinner screen facing the incident flux. The optimum ratio depends on the x-ray attenuation length in the screen.

Respiratory care in familial dysautonomia: Systematic review and expert consensus recommendations.

BACKGROUND: Familial dysautonomia (Riley-Day syndrome, hereditary sensory autonomic neuropathy type-III) is a rare genetic disease caused by impaired development of sensory and afferent autonomic nerves. As a consequence, patients develop neurogenic dysphagia with frequent aspiration, chronic lung disease, and chemoreflex failure leading to severe sleep disordered breathing. The purpose of these guidelines is to provide recommendations for the diagnosis and treatment of respiratory disorders in familial dysautonomia. METHODS: We performed a systematic review to summarize the evidence related to our questions. When evidence was not sufficient, we used data from the New York University Familial Dysautonomia Patient Registry, a database containing ongoing prospective comprehensive clinical data from 670 cases. The evidence was summarized and discussed by a multidisciplinary panel of experts. Evidence-based and expert recommendations were then formulated, written, and graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. RESULTS: Recommendations were formulated for or against specific diagnostic tests and clinical interventions. Diagnostic tests reviewed included radiological evaluation, dysphagia evaluation, gastroesophageal evaluation, bronchoscopy and bronchoalveolar lavage, pulmonary function tests, laryngoscopy and polysomnography. Clinical interventions and therapies reviewed included prevention and management of aspiration, airway mucus clearance and chest physical therapy, viral respiratory infections, precautions during high altitude or air-flight travel, non-invasive ventilation during sleep, antibiotic therapy, steroid therapy, oxygen therapy, gastrostomy tube placement, Nissen fundoplication surgery, scoliosis surgery, tracheostomy and lung lobectomy. CONCLUSIONS: Expert recommendations for the diagnosis and management of respiratory disease in patients with familial dysautonomia are provided. Frequent reassessment and updating will be needed.

Deriving depth-dependent light escape efficiency and optical Swank factor from measured pulse height spectra of scintillators.

PURPOSE: Pulse height spectroscopy has been used by investigators to deduce the imaging properties of scintillators. Pulse height spectra (PHS) are used to compute the Swank factor, which describes the variation in scintillator light output per x-ray interaction. The spread in PHS measured below the K-edge is related to the optical component of the Swank factor, i.e., variations in light escape efficiency from different depths of x-ray interaction in the scintillator, denoted ε¯(z). Optimizing scintillators for medical imaging applications requires understanding of these optical properties, as they determine tradeoffs between parameters such as x-ray absorption, light yield, and spatial resolution. This work develops a model for PHS acquisition such that the effect of measurement uncertainty can be removed. This method allows ε¯(z) to be quantified on an absolute scale and permits more accurate estimation of the optical Swank factor of scintillators. METHODS: The pulse height spectroscopy acquisition chain was modeled as a linear system of stochastic gain stages. Analytical expressions were derived for signal and noise propagation through the PHS chain, accounting for deterministic and stochastic aspects of x-ray absorption, scintillation, and light detection with a photomultiplier tube. The derived expressions were used to calculate PHS of thallium-doped cesium iodide (CsI) scintillators using parameters that were measured, calculated, or known from literature. PHS were measured at 25 and 32 keV of CsI samples designed with an optically reflective or absorptive backing, with or without a fiber-optic faceplate (FOP), and with thicknesses ranging from 150-1000 µm. Measured PHS were compared with calculated PHS, then light escape model parameters were varied until measured and modeled results reached agreement. Resulting estimates of ε¯(z) were used to calculate each scintillator's optical Swank factor. RESULTS: For scintillators of the same optical design, only minor differences in light escape efficiency were observed between samples with different thickness. As thickness increased, escape efficiency decreased by up to 20% for interactions furthest away from light collection. Optical design (i.e., backing and FOP) predominantly affected the magnitude and relative variation in ε¯(z). Depending on interaction depth and scintillator thickness, samples with an absorptive backing and FOP were estimated to yield 4.1-13.4 photons/keV. Samples with a reflective backing and FOP yielded 10.4-18.4 keV-1 , while those with a reflective backing and no FOP yielded 29.5-52.0 keV-1 . Optical Swank factors were approximately 0.9 and near-unity in samples featuring an absorptive or reflective backing, respectively. CONCLUSIONS: This work uses a modeling approach to remove the noise introduced by the measurement apparatus from measured PHS. This method allows absolute quantification of ε¯(z) and more accurate estimation of the optical Swank factor of scintillators. The method was applied to CsI scintillators with different thickness and optical design, and determined that optical design more strongly affects ε¯(z) and Swank factor than differences in CsI thickness. Despite large variations in ε¯(z) between optical designs, the Swank factor of all evaluated samples is above 0.9. Information provided by this methodology can help validate Monte Carlo simulations of structured CsI and optimize scintillator design for x-ray imaging applications.