Receipt Of Corticosteroids Research Articles

Evaluation of Etomidate Use and Association with Mortality Compared with Ketamine among Critically Ill Patients.

Rationale: Uncertainty remains regarding the risks associated with single-dose use of etomidate. Objectives: To assess the use of etomidate in critically ill patients and compare outcomes for patients who received etomidate versus ketamine. Methods: We assessed patients who received invasive mechanical ventilation (IMV) and were admitted to an ICU in the Premier Healthcare Database between 2008 and 2021. The exposure was receipt of etomidate on the day of IMV initiation, and the main outcome was hospital mortality. Using multivariable regression, we compared patients who received IMV within the first 2 days of hospitalization who received etomidate with propensity score-matched patients who received ketamine. We also assessed whether receipt of corticosteroids in the days after intubation modified the association between etomidate and mortality. Measurements and Main Results: Of 1,689,945 patients who received IMV, nearly half (738,855; 43.7%) received etomidate. Among those who received IMV in the first 2 days of hospitalization, we established 22,273 matched pairs administered either etomidate or ketamine. In the primary analysis, receipt of etomidate was associated with greater hospital mortality relative to ketamine (21.6% vs. 18.7%; absolute risk difference, 2.8%; 95% confidence interval, 2.1%, 3.6%; adjusted odds ratio, 1.28, 95% confidence interval, 1.21,1.34). This was consistent across subgroups and sensitivity analyses. We found no attenuation of the association with mortality with receipt of corticosteroids in the days after etomidate use. Conclusions: Use of etomidate on the day of IMV initiation is common and associated with a higher odds of hospital mortality than use of ketamine. This finding is independent of subsequent treatment with corticosteroids.

Incidence and outcomes of cytomegalovirus reactivation after chimeric antigen receptor T-cell therapy

AbstractCytomegalovirus (CMV) reactivation is a major complication among seropositive allogeneic hematopoietic cell transplantation recipients; however, data on CMV reactivation after chimeric antigen receptor (CAR) T-cell therapy are limited. We report the incidence and outcomes of 95 adult CMV-seropositive patients who received CAR T-cell therapy between February 2018 and February 2023. CMV outcomes were CMV reactivation (any viremia) and clinically significant CMV infection (cs-CMV). Thirty-one patients (33%) had evidence of CMV reactivation (any viremia), and 10 patients (11%) had cs-CMV. The median time from CAR T-cell infusion to CMV reactivation was 19 days (interquartile range [IQR], 9-31). The cumulative incidence of CMV (any viremia) was significantly higher among patients with grade 3 to 4 cytokine release syndrome (67 vs 28%; P = .01), and those who received corticosteroids (39 vs 21%; P = .03), anakinra (56 vs 28%; P = .02), or ≥2 immunosuppressants (41 vs 21%; P = .02). Receipt of corticosteroids (18 vs 0%; P = .004), tocilizumab (14 vs 0%; P = .04), anakinra (33 vs 7%; P = .008), and ≥2 immunosuppressants (20 vs 0%; P = .001) were all associated with cs-CMV. Receiving ≥2 immunosuppressants was associated with a twofold increase in CMV reactivation in multivariate analyses (adjusted odds ratio [aOR], 2.27; 95% confidence interval, 1.1-4.8; P = .03). Overall, the 1-year mortality was significantly higher in those with CMV reactivation (57% vs 23%; P = .001). Immunosuppression, particularly with corticosteroids, for the management of CAR T-cell toxicities, is a major risk factor for CMV reactivation.

Implementation of Recommendations on the Use of Corticosteroids in Severe COVID-19

Research diversity and representativeness are paramount in building trust, generating valid biomedical knowledge, and possibly in implementing clinical guidelines. To compare variations over time and across World Health Organization (WHO) geographic regions of corticosteroid use for treatment of severe COVID-19; secondary objectives were to evaluate the association between the timing of publication of the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial (June 2020) and the WHO guidelines for corticosteroids (September 2020) and the temporal trends observed in corticosteroid use by region and to describe the geographic distribution of the recruitment in clinical trials that informed the WHO recommendation. This prospective cohort study of 434 851 patients was conducted between January 31, 2020, and September 2, 2022, in 63 countries worldwide. The data were collected under the auspices of the International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC)-WHO Clinical Characterisation Protocol for Severe Emerging Infections. Analyses were restricted to patients hospitalized for severe COVID-19 (a subset of the ISARIC data set). Corticosteroid use as reported to the ISARIC-WHO Clinical Characterisation Protocol for Severe Emerging Infections. Number and percentage of patients hospitalized with severe COVID-19 who received corticosteroids by time period and by WHO geographic region. Among 434 851 patients with confirmed severe or critical COVID-19 for whom receipt of corticosteroids could be ascertained (median [IQR] age, 61.0 [48.0-74.0] years; 53.0% male), 174 307 (40.1%) received corticosteroids during the study period. Of the participants in clinical trials that informed the guideline, 91.6% were recruited from the United Kingdom. In all regions, corticosteroid use for severe COVID-19 increased, but this increase corresponded to the timing of the RECOVERY trial (time-interruption coefficient 1.0 [95% CI, 0.9-1.2]) and WHO guideline (time-interruption coefficient 1.9 [95% CI, 1.7-2.0]) publications only in Europe. At the end of the study period, corticosteroid use for treatment of severe COVID-19 was highest in the Americas (5421 of 6095 [88.9%]; 95% CI, 87.7-90.2) and lowest in Africa (31 588 of 185 191 [17.1%]; 95% CI, 16.8-17.3). The results of this cohort study showed that implementation of the guidelines for use of corticosteroids in the treatment of severe COVID-19 varied geographically. Uptake of corticosteroid treatment was lower in regions with limited clinical trial involvement. Improving research diversity and representativeness may facilitate timely knowledge uptake and guideline implementation.

Longitudinal patient-reported outcomes in patients receiving chimeric antigen receptor T-cell therapy.

Chimeric antigen receptor T-cell therapy (CAR-T) has transformed the treatment for relapsed/refractory hematologic malignancies; however, data on patient-reported outcomes in CAR-T are limited. We conducted a longitudinal study of adults with hematologic malignancies receiving CAR-T. We assessed quality of life (QOL; functional assessment of cancer therapy-general), psychological distress (hospital anxiety and depression scale, patient health questionnaire-9, posttraumatic stress disorder [PTSD] checklist), and physical symptoms (Edmonton symptom assessment scale-revised) at baseline, 1week, 1, 3, and 6months after CAR-T. We used linear mixed models to identify factors associated with QOL trajectory. We enrolled 103 of 142 eligible patients (3 did not receive CAR-T). QOL (B= 1.96; P< .001) and depression (B=-0.32; P= .001) worsened by 1week and improved by 6months after CAR-T. At 6months, 18%, 22%, and 22% reported clinically significant depression, anxiety, and PTSD symptoms, respectively. At 1week, 52% reported severe physical symptoms, declining to 28% at 6months after CAR-T. In unadjusted linear mixed models, worse Eastern Cooperative Oncology Group performance status (B= 1.24; P= .042), receipt of tocilizumab (B= 1.54; P= .042), and receipt of corticosteroids for cytokine release syndrome and/or neurotoxicity (B= 2.05; P= .006) were associated with higher QOL trajectory. After CAR-T, QOL declined, and depression increased early, followed by improvements in QOL, psychological distress, and physical symptoms by6months after infusion. A significant minority of patients reported substantial psychological distress and physical symptoms longitudinally.

Impact of Adjunct Corticosteroid Therapy on Quality of Life for Children With Suspected Pneumonia.

To determine the association between adjunct corticosteroid therapy and quality of life (QoL) outcomes in children with signs and symptoms of lower respiratory tract infection and clinical suspicion for community-acquired pneumonia (CAP) in the emergency department (ED). Secondary analysis from a prospective cohort study of children aged 3 months to 18 years with signs and symptoms of LRTI and a chest radiograph for suspected CAP in the ED, excluding children with recent (within 14 days) systemic corticosteroid use. The primary exposure was receipt of corticosteroids during the ED visit. Outcomes were QoL measures and unplanned visits. Multivariable regression was used to evaluate the association between corticosteroid therapy and outcomes. Of 898 children, 162 (18%) received corticosteroids. Children who received corticosteroids were more frequently boys (62%), Black (45%), had history of asthma (58%), previous pneumonia (16%), presence of wheeze (74%), and more severe illness at presentation (6%). Ninety-six percent were treated for asthma as defined by report of asthma or receipt of ß-agonist in the ED. Receipt of corticosteroids was not associated with QoL measures: days of activity missed (adjusted incident rate ratio [aIRR], 0.84; 95% confidence interval [CI], 0.63-1.11) and days of work missed (aIRR, 0.88; 95% CI, 0.60-1.27). There was a statistically significant interaction between age (>2 years) and corticosteroids receipt; the patients had fewer days of activity missed (aIRR, 0.62; 95% CI, 0.46-0.83), with no effect on children 2 years or younger (aIRR, 0.83; 95% CI, 0.54-1.27). Corticosteroid treatment was not associated with unplanned visit (odds ratio, 1.37; 95% CI, 0.69-2.75). In this cohort of children with suspected CAP, receipt of corticosteroids was associated with asthma history and was not associated with missed days of activity or work, except in a subset of children aged older than 2 years.

Frailty: A Strong Impact on Lung Transplant Outcomes?

Frailty: A Strong Impact on Lung Transplant Outcomes?

Impact of initial fluid resuscitation volume on clinical outcomes in patients with heart failure and septic shock

BackgroundFluid resuscitation is a key treatment for sepsis, but limited data exists in patients with existing heart failure (HF) and septic shock. The objective of this study was to determine the impact of initial fluid resuscitation volume on outcomes in HF patients with reduced or mildly reduced left ventricular ejection fraction (LVEF) with septic shock. MethodsThis multicenter, retrospective, cohort study included patients with known HF (LVEF ≤50%) presenting with septic shock. Patients were divided into two groups based on the volume of fluid resuscitation in the first 6 h; <30 mL/kg or ≥30 mL/kg. The primary outcome was a composite of in-hospital mortality or renal replacement therapy (RRT) within 7 days. Secondary outcomes included acute kidney injury (AKI), initiation of mechanical ventilation, and length of stay (LOS). All related data were collected and compared between the two groups. A generalized logistic mixed model was used to assess the association between fluid groups and the primary outcome while adjusting for baseline LVEF, Acute Physiology and Chronic Health Evaluation (APACHE) II score, inappropriate empiric antibiotics, and receipt of corticosteroids. ResultsOne hundred and fifty-four patients were included (93 patients in <30 mL/kg group and 61 patients in ≥30 mL/kg group). The median weight-based volume in the first 6 h was 17.7 (12.2–23.0) mL/kg in the <30 mL/kg group vs. 40.5 (34.2–53.1) mL/kg in the ≥30 mL/kg group (P <0.01). No statistical difference was detected in the composite of in-hospital mortality or RRT between the <30 mL/kg group compared to the ≥30 mL/kg group (55.9% vs. 45.9%, P=0.25), respectively. The <30 mL/kg group had a higher incidence of AKI, mechanical ventilation, and longer hospital LOS. ConclusionsIn patients with known reduced or mildly reduced LVEF presenting with septic shock, no difference was detected for in-hospital mortality or RRT in patients who received ≥30 mL/kg of resuscitation fluid compared to less fluid, although this study was underpowered to detect a difference. Importantly, ≥30 mL/kg fluid did not result in a higher need for mechanical ventilation.

Systemic postnatal corticosteroid use for the prevention of bronchopulmonary dysplasia and its relationship to early neurodevelopment in extremely preterm infants

BackgroundSystemic postnatal corticosteroid use in extremely preterm infants poses a risk of adverse neurodevelopmental outcomes. This study explores their use beyond seven days of age with early neurodevelopmental assessments during the fidgety period (9–20 weeks postterm age).MethodsThis retrospective single-center cohort study included inborn extremely preterm infants from 1 January 2014 to 31 December 2018. Outborn infants, those with congenital or genetic abnormalities, and those who received postnatal corticosteroids for nonrespiratory reasons were excluded. The cohort was dichotomized based on the status of corticosteroid receipt. Early neurodevelopmental outcomes were reported using Prechtl’s General Movements Assessment.ResultsOf the 282 infants, 67 (23.75%) received corticosteroids. Of these, 34 (50.75%) received them for dependency on invasive ventilation (intermittent positive-pressure ventilation), and the remainder received them for dependency on non-invasive ventilation continuous positive airway pressure (CPAP) or bi-level positive airway pressure (BiPAP). Abnormal or absent fidgety movements were observed in 13% of infants (7/54) who received corticosteroids compared to 2% of infants (3/146) who did not. An increased odds for an abnormal general movements assessment from corticosteroid use after adjusting for gestational age [adjusted odds ratio (aOR) = 5.5, 95% confidence interval (CI) = 1.14–26.56] was observed. The motor optimality scores differed between the two groups [corticosteroid group: 25.5 (23–26) versus no-corticosteroid group: 26 (24–28); z = − 2.02]. A motor optimality score < 20 was observed in 14.8% of infants (8/54) in the corticosteroid group compared to 2% of infants (3/146) in the noncorticosteroid group. This difference was significant after adjustment for gestational age (aOR 5.96, 95% CI 1.28–27.74).ConclusionsAbnormal early neurodevelopment was observed in infants who received systemic postnatal corticosteroids. The relationship between these findings and other factors influencing early neurodevelopment needs further exploration.

2029. Risk factors for a Central Line Associated Bloodstream Infection Amongst Hospitalized Patients with COVID

Abstract Background Central line associated bloodstream infections (CLABSI) are serious healthcare associated infections. During the COVID pandemic, we observed an increased incidence of CLABSIs in our healthcare system. We sought to identify risk factors for CLABSI among patients with COVID. Methods We performed a single-center, matched case-control study in patients admitted between Mar 2020 and Dec 2020 who were 1) diagnosed with COVID based on laboratory results or diagnosis code, and who were 2) at risk for developing a CLABSI based on the presence of a central line for ≥3 days. Cases were those diagnosed, based on National Healthcare Safety Network criteria, with CLABSI; controls were patients not diagnosed with CLABSI. Cases and controls were 1:4 matched based on age at admission (+/- 5 years) and COVID diagnosis date (+/- 45 days). Descriptive statistics were calculated for continuous and categorical variables. For comparisons, p values are from generalized estimating equations accounting for clustering by case-control matches. All analyses were performed in SAS version 9.4 (SAS Institute Inc., Cary, NC). Approval was granted by our institutional IRB. Results Characteristics of the patients who were diagnosed with COVID and at risk for developing a CLABSI are presented in table 1. Compared to patients with COVID and no CLABSI, patients with a CLABSI were more likely to be of a non-white race (p=0.0435). A longer length of stay was observed among CLABSI patients, (p=0.0011) and patients with CLABSI were less likely to be discharged to home (p=0.0084). There was a non-statistically significant trend toward a history of diabetes (p=0.0554), receipt of corticosteroids (p=0.052) and receipt of tocilizumab (p=0.0952) among CLABSI patients. Conclusion Patients hospitalized for COVID who developed a CLABSI had longer hospitalizations and were less likely to be discharged home. Race other than white was a risk factor for CLABSI among patients with COVID. The relationships between race, racism, and CLABSI should be further explored. Disclosures All Authors: No reported disclosures.

Clinical Outcomes of Zinc Supplementation Among COVID-19 Patients

Zinc supplementation is frequently prescribed during the treatment of COVID-19. However, the evidence supporting the efficacy of this intervention is mixed. Establish the clinical utility of zinc supplementation to alter disease severity in COVID- 19 illness. We performed a multicenter, retrospective, observational chart review of patients admitted to Ascension St. John Hospital or Detroit Medical Center from January 1st, 2020 to May 31st, 2020. All included patients received concomitant hydroxychloroquine due to its zinc ionophore activity. Our primary outcome was a change in Sequential Organ Failure Assessment (SOFA) score with secondary outcomes including all-cause mortality, need for intubation, and QTc prolongation as a safety outcome. We identified 489 patients who received zinc and 587 patients who did not. The primary outcome showed a small difference in the change in SOFA score in patients receiving zinc in univariate analysis (1.08 vs. 1.43, p=0.02), but this difference was not significant after adjustment for confounding factors such as receipt of corticosteroids and ICU admission. Mortality was not different between those that received zinc compared to those that did not (32.7% vs. 35.9%, p=0.268). Our retrospective study, including 1064 patients hospitalized in Detroit, demonstrated no differences in mortality or disease severity with zinc combination. Furthermore, prospective studies are needed to establish the utility of zinc in the treatment of COVID-19.

Invasive Aspergillosis in Patients with Acute Leukemia: Comparison Between Acute Myeloid and Acute Lymphoid Leukemia.

The epidemiology of invasive aspergillosis (IA) in patients with acute lymphoid leukemia (ALL) has not been well characterized. To identify potential peculiarities in the natural history, treatment response and outcome of IA diagnosed in patients with ALL and AML. This is a retrospective cohort study conducted in seven tertiary-care hospitals between 2009 and 2017 of all consecutive episodes of IA occurring in adult patients with acute leukemia. Demographic characteristics, underlying disease and recent treatment, antifungal prophylaxis, neutropenia, receipt of corticosteroids, clinical and radiological findings, mycological results, antifungal therapy, and 6-week and 12-week survival were recorded. We identified 77 cases of IA in 54 patients with AML and 23 patients with ALL. The majority of patients developed IA in the context of induction chemotherapy for newly diagnosed (48.0%) or relapsed (41.6%) leukemia, with no differences between ALL and AML. Lung involvement was more frequent in AML (96.3% vs. 82.6%, p = 0.06) and rhinosinusitis was more common in ALL (43.5% vs. 24.1%, p = 0.09). Galactomannan was the microbiologic documentation of IA in 76.6%, with similar patterns of positivity in AML and ALL. The 6-week survival of IA in patients with AML and ALL was 63.0% and 56.5%, respectively (p = 0.60). The epidemiology, clinical presentation, diagnosis and outcome of IA in ALL patients are similar to patients with AML.

Single-Fraction vs. Fractionated Radiosurgery and the Development of Post-Treatment Hemorrhage for Intact Melanoma Brain Metastases

<h3>Purpose/Objective(s)</h3> To assess whether intracranial stereotactic radiotherapy fractionation is associated with increased risk of post-treatment lesional hemorrhage in patients with intact melanoma brain metastases (MBM). <h3>Materials/Methods</h3> A single institution retrospective review was performed of patients with previously unresected MBM treated with robotic SRS/fSRT between 2013 to 2021. The presence of lesional hemorrhage was determined by multi-disciplinary neuroradiology review of magnetic resonance imaging (MRI). Dosimetric variables were reported as biologically effective doses using an estimated α/β ratio of 2.5 (BED_2.5) for melanoma to permit comparison across varying fractionation schedules. The effect of fractionation and additional prognostic factors on the rate of post-treatment development of hemorrhage was statistically analyzed using logistic regression with random effects to account for interactions between lesions of the same patient. A Cox model was used for local control (LC) with a frailty term to account for dependence between lesions. <h3>Results</h3> The cohort included 48 patients with 226 intact MBM treated with SRS/fSRT. Evidence of hemorrhage prior to treatment was demonstrated in 69 of 226 metastases (30.5%). For lesions without signs of prior hemorrhage, 65 of 157 (41.4%) demonstrated evidence of hemorrhage after radiosurgical treatment. 63 of 133 lesions (47.4%) receiving single-fraction SRS demonstrated evidence of post-treatment hemorrhage versus 2 of 24 lesions (8.3%) treated with fSRT (<i>p=0.01</i>). Treatment factors including lesion size, prescription isodose line, as well as receipt of corticosteroids, targeted, or immune therapy were not predictive of hemorrhage occurrence. A larger maximum BED_2.5 was observed in lesions developing hemorrhage compared to no hemorrhage (mean 238.3 Gy vs. 211.4 Gy; <i>p=0.022</i>). LC at twelve-months was 65.7% (95% CI 37.2-87.3%) and 77.5% (95% CI 58.5-91.2%) for lesions demonstrating pre-treatment and post-treatment hemorrhage, respectively, with no local failure events observed in non-hemorrhagic lesions (<i>p=<0.001</i>). <h3>Conclusion</h3> Intact MBM without prior evidence of hemorrhage receiving single-fraction SRS were associated with an increased incidence of post-treatment hemorrhage when compared to those treated with fractionated stereotactic radiotherapy. The presence of lesion hemorrhage, either pre- or post-treatment, was associated with inferior local control. Post-treatment hemorrhage was correlated with a larger maximum BED_2.5. Further investigations of the clinical impact of lesional hemorrhage, factors influencing lesion control, as well as optimal dose and fractionation schedules for treatment of MBM in the era of immunotherapy are warranted.

Effect of COVID 19 pneumonia on hyperglycemia: Is it different from non COVID pneumonia?

Background and aimsGlycemic control in critical illness has been linked to outcomes. We sought to investigate if COVID pneumonia was causing disrupted glycemic control compared to historically similar diseases. MethodsAt Intermountain Healthcare, a 23-hospital healthcare system in the intermountain west, we performed a multicenter, retrospective cohort observational study. We compared 13,268 hospitalized patients with COVID pneumonia to 6673 patients with non -COVID-pneumonia. ResultsPatients with COVID-19 were younger had fewer comorbidities, had lower mortality and greater length of hospital stay. Our regression models demonstrated that daily insulin dose, indexed for weight, was associated with COVID-19, age, diabetic status, HgbA1c, admission SOFA, ICU length of stay and receipt of corticosteroids. There was significant interaction between a diagnosis of diabetes and having COVID-19. Time in range for our IV insulin protocol was not correlated with having COVID after adjustment. It was correlated with ICU length of stay, diabetic control (HgbA1C) and prior history of diabetes. Among patients with subcutaneous (SQ) insulin only percent of glucose checks in range was correlated with diabetic status, having Covid-19, HgbA1c, total steroids given and Elixhauser comorbidity score even when controlled for other factors. ConclusionsHospitalized patients with COVID-19 pneumonia who receive insulin for glycemic control require both more SQ and IV insulin than the non-COVID-19 pneumonia counterparts. Patients with COVID-19 who received SQ insulin only had a lower percent of glucose checks in range.

The Landscape of Candidemia During the Coronavirus Disease 2019 (COVID-19) Pandemic.

The COVID-19 pandemic has resulted in unprecedented healthcare challenges, and COVID-19 has been linked to secondary infections. Candidemia, a fungal healthcare-associated infection, has been described in patients hospitalized with severe COVID-19. However, studies of candidemia and COVID-19 coinfection have been limited in sample size and geographic scope. We assessed differences in patients with candidemia with and without a COVID-19 diagnosis. We conducted a case-level analysis using population-based candidemia surveillance data collected through the Centers for Disease Control and Prevention's Emerging Infections Program during April-August 2020 to compare characteristics of candidemia patients with and without a positive test for COVID-19 in the 30 days before their Candida culture using chi-square or Fisher's exact tests. Of the 251 candidemia patients included, 64 (25.5%) were positive for SARS-CoV-2. Liver disease, solid-organ malignancies, and prior surgeries were each >3 times more common in patients without COVID-19 coinfection, whereas intensive care unit-level care, mechanical ventilation, having a central venous catheter, and receipt of corticosteroids and immunosuppressants were each >1.3 times more common in patients with COVID-19. All-cause in-hospital fatality was 2 times higher among those with COVID-19 (62.5%) than without (32.1%). One-quarter of candidemia patients had COVID-19. These patients were less likely to have certain underlying conditions and recent surgery commonly associated with candidemia and more likely to have acute risk factors linked to COVID-19 care, including immunosuppressive medications. Given the high mortality, it is important for clinicians to remain vigilant and take proactive measures to prevent candidemia in patients with COVID-19.

A ten-year surveillance of P aeruginosa bloodstream infections in a tertiary care hospital: Trends and risk factors for mortality.

Pseudomonas aeruginosa (P aeruginosa) is a leading cause of nosocomial bloodstream infections worldwide. This study aimed to evaluate the incidence of P aeruginosa bloodstream infections and to identify predictors of 30-day mortality. A retrospective study was conducted in an academic tertiary hospital in Jordan. The medical records of patients hospitalised over ten years (1 January 2008-31 December 2017) were reviewed to identify patients' positive blood culture of P aeruginosa. Annual incidence, antimicrobial susceptibility patterns and risk factors for 30-day mortality were analysed. A total of 169 cases of P aeruginosa bloodstream infection were identified, with an overall incidence rate of 0.23 case/1000 admission. The overall crude 30-day mortality was 36.7%. Receipt of corticosteroids (OR = 4.5; P=.0017), severe sepsis and septic shock (OR = 2.7; P=.0476), admission to intensive care unit (OR = 5.9; P=.0004), end-stage renal disease (OR = 4.1; P=.0123), inappropriate empirical therapy (OR = 3.2; P=.0143) and inappropriate definitive therapy (OR = 2.9; P=.0110) were identified as independent risk factors for mortality. The annual incidence of P aeruginosa BSIs was fluctuating over ten years period. Several predictors for 30-day mortality in patients with P aeruginosa BSIs were identified, including inappropriate empirical and definitive therapy.

Morbidity and mortality reduction associated with polysomnography testing in idiopathic pulmonary fibrosis: a population-based cohort study

BackgroundIt is not well-known if diagnosing and treating sleep breathing disorders among individuals with idiopathic pulmonary fibrosis (IPF) improves health outcomes. We evaluated the association between receipt of laboratory-based polysomnography (which is the first step in the diagnosis and treatment of sleep breathing disorders in Ontario, Canada) and respiratory-related hospitalization and all-cause mortality among individuals with IPF.MethodsWe used a retrospective, population-based, cohort study design, analyzing health administrative data from Ontario, Canada, from 2007 to 2019. Individuals with IPF were identified using an algorithm based on health administrative codes previously developed by IPF experts. Propensity score matching was used to account for potential differences in 41 relevant covariates between individuals that underwent polysomnography (exposed) and individuals that did not undergo polysomnography (controls), in order minimize potential confounding. Respiratory-related hospitalization and all-cause mortality were evaluated up to 12 months after the index date.ResultsOut of 5044 individuals with IPF identified, 201 (4.0%) received polysomnography, and 189 (94.0%) were matched to an equal number of controls. Compared to controls, exposed individuals had significantly reduced rates of respiratory-related hospitalization (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.24–0.75), p = 0.003) and all-cause mortality (HR 0.49, 95% CI 0.30–0.80), p = 0.004). Significantly reduced rate of respiratory-related hospitalization (but not all-cause mortality) was also observed among those with > = 1 respiratory-related hospitalization (HR 0.38, 95% CI 0.15–0.99) and systemic corticosteroid receipt (HR 0.37, 95% CI 0.19–0.94) in the year prior to the index date, which reflect sicker subgroups of persons.ConclusionsUndergoing polysomnography was associated with significantly improved clinically-important health outcomes among individuals with IPF, highlighting the potential importance of incorporating this testing in IPF disease management.

Clinical characteristics and risk factors for the isolation of multi-drug-resistant Gram-negative bacteria from critically ill patients with COVID-19

BackgroundWe investigated the clinical characteristics and risk factors for the isolation of multi-drug-resistant (MDR) Gram-negative bacteria (GNB) from critically ill COVID-19 patients.MethodsWe retrospectively matched (1:2) critical COVID-19 patients with one or more MDR GNB from any clinical specimen (cases), with those with no MDR GNB isolates (controls).ResultsSeventy-eight cases were identified (4.5 per 1000 intensive care unit (ICU) days, 95% confidence interval (CI) 3.6–5.7). Of 98 MDR GNB isolates, the most frequent species were Stenotrophomonas maltophilia (24, 24.5%), and Klebsiella pneumoniae (23, 23.5%). Two (8.7%) K. pneumoniae, and six (85.7%) Pseudomonas aeruginosa isolates were carbapenem resistant. A total of 24 (24.5%) isolates were not considered to be associated with active infection. Those with active infection received appropriate antimicrobial agents within a median of one day. The case group had significantly longer median central venous line days, mechanical ventilation days, and hospital length of stay (P<0.001 for each). All-cause mortality at 28 days was not significantly different between the two groups (P=0.19). Mechanical ventilation days (adjusted odds ratio 1.062, 95% CI 1.012–1.114; P=0.015), but not receipt of corticosteroids or tocilizumab, was independently associated with the isolation of MDR GNB. There was no association between MDR GNB and 28-day all-cause mortality (adjusted odds ratio 2.426, 95% CI 0.833–7.069; P= 0.104).ConclusionIn critically ill COVID-19 patients, prevention of MDR GNB colonization and infections requires minimizing the use of invasive devices, and to remove them as soon as their presence is no longer necessary.

Immune reconstitution and infectious complications following axicabtagene ciloleucel therapy for large B-cell lymphoma

Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has significantly improved outcomes in the treatment of refractory or relapsed large B-cell lymphoma (LBCL). We evaluated the long-term course of hematologic recovery, immune reconstitution, and infectious complications in 41 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) at a single center. Grade 3+ cytopenias occurred in 97.6% of patients within the first 28 days postinfusion, with most resolved by 6 months. Overall, 63.4% of patients received a red blood cell transfusion, 34.1% of patients received a platelet transfusion, 36.6% of patients received IV immunoglobulin, and 51.2% of patients received growth factor (granulocyte colony-stimulating factor) injections beyond the first 28 days postinfusion. Only 40% of patients had recovered detectable CD19+ B cells by 1 year, and 50% of patients had a CD4+ T-cell count <200 cells per μL by 18 months postinfusion. Patients with durable responses to axi-cel had significantly longer durations of B-cell aplasia, and this duration correlated strongly with the recovery of CD4+ T-cell counts. There were significantly more infections within the first 28 days compared with any other period of follow-up, with the majority being mild-moderate in severity. Receipt of corticosteroids was the only factor that predicted risk of infection in a multivariate analysis (hazard ratio, 3.69; 95% confidence interval, 1.18-16.5). Opportunistic infections due to Pneumocystis jirovecii and varicella-zoster virus occurred up to 18 months postinfusion in patients who prematurely discontinued prophylaxis. These results support the use of comprehensive supportive care, including long-term monitoring and antimicrobial prophylaxis, beyond 12 months after axi-cel treatment.

Do high MICs predict the outcome in invasive fusariosis?

Invasive fusariosis (IF) affects mostly severely immunocompromised hosts and is associated with poor outcome. Since Fusarium species exhibit high MICs for most antifungal agents, this could explain the poor prognosis. However, a clear-cut correlation between MIC and outcome has not been established. To evaluate the correlation between MIC and outcome (6 week death rate) in patients with IF. We performed a multicentre retrospective study of patients with IF who received treatment and had MIC levels determined by EUCAST or CLSI for the drug(s) used during treatment. We compared the MIC50 and MIC distribution among survivors and patients who died within 6 weeks from the diagnosis of IF. Among 88 patients with IF, 74 had haematological diseases. Primary treatment was monotherapy in 52 patients (voriconazole in 27) and combination therapy in 36 patients (liposomal amphotericin B + voriconazole in 23). The MIC50 and range for the five most frequent agents tested were: voriconazole 8 mg/L (range 0.5-64), amphotericin B 2 mg/L (range 0.25-64), posaconazole 16 mg/L (range 0.5-64), itraconazole 32 mg/L (range 4-64), and isavuconazole 32 mg/L (range 8-64). There was no difference in MIC50 and MIC distribution among survivors and patients who died. By contrast, persistent neutropenia and receipt of corticosteroids were strong predictors of 6 week mortality. Our study did not show any correlation between MIC and mortality at 6 weeks in patients with IF.

Characteristics and risk factors for microbial infections during cancer immune checkpoint therapy.

ABSTRACTThe risk of infection in patients receiving immune checkpoint inhibitor (ICI) therapy is not well understood. Immune‐related adverse events requiring immunosuppressive therapy may impact infection risk. ICIs may induce an exaggerated immune response to latent infection. We assessed the incidence and risk factors for infections during cancer ICI therapy. A retrospective chart review of solid tumor patients treated with ICIs was conducted. Infectious episodes were defined as those where a microbial organism was cultured or identified through polymerase chain reaction. Infections which occurred during and up to 1 year following ICI therapy were considered “post‐ICI” infections. Of 327 patients, 47% had melanoma and 36% had non‐small cell lung cancer. The majority (77%) received single agent anti‐PD(L)1 antibody, 14% received combination anti‐PD(L)1 and anti‐CTLA4 antibody, and 9% single agent anti‐CTLA4 antibody. Infections occurred in 89 (27%) in the post‐ICI compared with 111 (34%) patients in the pre‐ICI period (p = 0.57). The most common types of infection were respiratory, genitourinary, and cutaneous infections. On multivariate analysis, only age over 67 years significantly predicted for development of infection on ICI (HR 1.73, p = 0.04). We did not find receipt of corticosteroids, combination ICI therapy, diabetes, or gender to significantly impact on infection risk. The rate of microbial infections among solid tumor patients receiving ICI therapy was 27%, comparable to the infection rate of 34% in the same cohort of patients in the period pre‐ICI therapy. Age over 67 years was significantly associated with infection post‐ICI.