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Rationale: Current guidelines recommend patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia receive empirical antibiotics for suspected bacterial superinfection on the basis of weak evidence. Rates of ventilator-associated pneumonia (VAP) in clinical trials of patients with SARS-CoV-2 pneumonia are unexpectedly low. Objectives: We conducted an observational single-center study to determine the prevalence and etiology of bacterial superinfection at the time of initial intubation and the incidence and etiology of subsequent bacterial VAP in patients with severe SARS-CoV-2 pneumonia. Methods: Bronchoscopic BAL fluid samples from all patients with SARS-CoV-2 pneumonia requiring mechanical ventilation were analyzed using quantitative cultures and a multiplex PCR panel. Actual antibiotic use was compared with guideline-recommended therapy. Measurements and Main Results: We analyzed 386 BAL samples from 179 patients with SARS-CoV-2 pneumonia requiring mechanical ventilation. Bacterial superinfection within 48 hours of intubation was detected in 21% of patients. Seventy-two patients (44.4%) developed at least one VAP episode (VAP incidence rate = 45.2/1,000 ventilator days); 15 (20.8%) initial VAPs were caused by difficult-to-treat pathogens. The clinical criteria did not distinguish between patients with or without bacterial superinfection. BAL-based management was associated with significantly reduced antibiotic use compared with guideline recommendations. Conclusions: In patients with SARS-CoV-2 pneumonia requiring mechanical ventilation, bacterial superinfection at the time of intubation occurs in <25% of patients. Guideline-based empirical antibiotic management at the time of intubation results in antibiotic overuse. Bacterial VAP developed in 44% of patients and could not be accurately identified in the absence of microbiologic analysis of BAL fluid.

Objectives: Determine the variation in outcomes and respiratory mechanics between the subjects who are intubated earlier versus later in their coronavirus disease 2019 course., Design: Retrospective cohort study., Setting: Northwestern Memorial Hospital ICUs., Patients: All patients intubated for coronavirus disease 2019 between March 2020 and June 2020., Interventions: Patients were stratified by time to intubation: 30 subjects were intubated 4-24 hours after presentation and 24 subjects were intubated 5-10 days after presentation. Baseline characteristics, hospitalization, ventilator mechanics, and outcomes were extracted and analyzed. Ten clinically available CT scans were manually reviewed to identify evidence of pulmonary vascular thrombosis and intussusceptive angiogenesis., Measurements and Main Results: Median time from symptom onset to intubation was significantly different between the early and late intubation cohorts, with the latter being intubated later in the course of their illness (7.9 vs 11.8 d; p = 0.04). The early intubation cohort had a lower mortality rate than the late intubation cohort (6% vs 30%, p < 0.001) without significantly different respiratory mechanics at the time of intubation. The late intubation cohort was noted to have higher dead space ratio (0.40 vs 0.52; p = 0.03). On review of CT scans, the late intubation cohort also had more dilated peripheral segments on imaging (two segments vs five segments)., Conclusions: The question as to whether delaying intubation is beneficial or harmful for patients with coronavirus disease 2019-induced hypoxemic respiratory failure has yet to be answered. As our approaches to coronavirus disease 2019 continue to evolve, the decision of timing of intubation remains paramount. Although noninvasive ventilation may allow for delaying intubation, it is possible that there are downstream effects of delayed intubation that should be considered, including the potential for pulmonary vascular thrombosis and intussusceptive angiogenesis with delayed intubation., Competing Interests: Dr. Cuttica reports personal fees from Actelion Pharmaceuticals, personal fees from Bayer, personal fees from United Therapeutics, personal fees from Gilead, and other from Reatta Pharmaceuticals, outside the submitted work. Dr. Agarwal reports personal fees from Boehringer Ingelheim Pharmaceuticals, outside the submitted work. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Severe community-acquired pneumonia secondary to SARS-CoV-2 is a leading cause of death. Current guidelines recommend patients with SARS-CoV-2 pneumonia receive empirical antibiotic therapy for suspected bacterial superinfection, but little evidence supports these recommendations., Methods: We obtained bronchoscopic bronchoalveolar lavage (BAL) samples from patients with SARS-CoV-2 pneumonia requiring mechanical ventilation. We analyzed BAL samples with multiplex PCR and quantitative culture to determine the prevalence of superinfecting pathogens at the time of intubation and identify episodes of ventilator-associated pneumonia (VAP) over the course of mechanical ventilation. We compared antibiotic use with guideline-recommended care., Results: The 179 ventilated patients with severe SARS-CoV-2 pneumonia discharged from our hospital by June 30, 2020 were analyzed. 162 (90.5%) patients had at least one BAL procedure; 133 (74.3%) within 48 hours after intubation and 112 (62.6%) had at least one subsequent BAL during their hospitalization. A superinfecting pathogen was identified within 48 hours of intubation in 28/133 (21%) patients, most commonly methicillin-sensitive Staphylococcus aureus or Streptococcus species (21/28, 75%). BAL-based treatment reduced antibiotic use compared with guideline-recommended care. 72 patients (44.4%) developed at least one VAP episode. Only 15/72 (20.8%) of initial VAPs were attributable to multidrug-resistant pathogens. The incidence rate of VAP was 45.2/1000 ventilator days., Conclusions: With use of sensitive diagnostic tools, bacterial superinfection at the time of intubation is infrequent in patients with severe SARS-CoV-2 pneumonia. Treatment based on current guidelines would result in substantial antibiotic overuse. The incidence rate of VAP in ventilated patients with SARS-CoV-2 pneumonia are higher than historically reported.

Purpose: Pulmonary vein isolation (PVI) by cryoballoon ablation (CBA) has emerged as a commonly used technique for the treatment of atrial fibrillation. We sought to explore the incidence, risk factors for, and characterization of post-CBA-PVI atrial flutter., Methods: We analyzed a prospective registry of patients who underwent CBA-PVI at a single institution. We included patients with more than 3 months of follow-up data and excluded those with a history of cavotricuspid isthmus (CTI) ablation. Locations of post-CBA-PVI atrial flutters were determined by analysis of intracardiac electrograms and electroanatomic maps., Results: There were 556 patients included in the analysis. The mean age was 61.0 ± 10.6 years, 67.4% were male, the number of failed anti-arrhythmic medication trials was 1.2 ± 0.8, and the duration of atrial fibrillation pre-CBA was 54.3 ± 69.1 months. The 28-mm second-generation cryoballoon was used almost exclusively. Over a median follow-up time of 22.7 ± 17.9 months, 25 (4.5%) patients developed post-CBA-PVI atrial flutter after the 3-month blanking period. Of those 25 patients, 15 (60%) underwent subsequent ablation to eliminate the atrial flutter circuit, with 60% being CTI-dependent and the remainder left-sided (p value not significant). Risk factors for the development of atrial flutter included NYHA class ≥ 2 (OR 5.02, p < 0.001), presence of baseline bundle branch block (OR 4.33, p = 0.006), and left ventricular ejection fraction < 50% (OR 3.36, p = 0.007)., Conclusions: The rate of post-CBA-PVI atrial flutter is low after the blanking period even with medium-term follow-up. The origin of atrial flutter is equally divided between the right and left atria.

Background: While several studies have evaluated predictors for atrial fibrillation (AF) recurrence following catheter ablation, there are limited data specific to cryoballoon ablation (CBA)., Methods: We analyzed a prospective registry of patients at a single institution who underwent CBA. Recurrence of AF (RAF) was defined as recurrence of AF by 12-month follow-up, excluding the 3-month blanking period. Univariate analysis was performed to evaluate predictors of RAF. Receiver operating characteristic analysis was used to compare and evaluate the performance of various risk scores for discriminating risk of RAF., Results: There were 542 patients included in the analysis with mean age 61.3 ± 10.6 years, 67.9% male, and 51.6% paroxysmal AF (PAF). Overall, only left atrial diameter (LAD) > 40 mm and ERAF (early recurrence of AF within 0-3 month blanking period) were significant predictors of RAF. In the PAF specific subgroup, LAD > 40 mm, AF duration > 12 months, prior stroke or transient ischemic attack, ERAF, and having previously failed an antiarrhythmic drug were significant predictors of RAF. In persistent AF (PeAF) subgroup, obstructive sleep apnea (OSA) and ERAF were significant predictors of RAF. Out of clinical risk scores tested, BASEAF2 had the highest performance with area under the curve of 0.646 (95% confidence interval [0.548, 0.708]; P < .01)., Conclusions: In this single-center retrospective study of CBA, we found only LAD > 40 mm and ERAF to be predictors of RAF. We identified OSA as a potential targetable risk factor in PeAF patients undergoing CBA. Out of risk scores tested for discriminating risk of RAF, BASEAF2 had the best performance., (© 2019 Wiley Periodicals, Inc.)

Lifestyle modification is the cornerstone of preventing atherosclerotic cardiovascular disease. When this is not sufficient in reducing risk, statin therapy is first line. Heart Outcomes Prevention Evaluation (HOPE-3) was a randomized controlled trial of rosuvastatin versus placebo, which demonstrated a significant net benefit in a lower-risk population without known atherosclerotic cardiovascular disease. There were many novel characteristics about this trial that should not be overlooked. It contained a diverse population and was the first trial to base inclusion solely on easily ascertainable metabolic risk factors. It had high adherence in the statin arm, likely due to several factors, including a run-in phase, close follow-up, and low intolerance of moderate-dose rosuvastatin. Attempting to simulate these could increase adherence among clinic populations. Although HOPE-3 did not demonstrate a significant decrease in cardiovascular events among women, meta-analysis including prior randomized controlled trials still demonstrates significant benefit, supporting prior guidelines for statin therapy in this group. Finally, HOPE-3 provides data that potentially support the legacy effect of statins. Understanding these key points provides additional insight into the benefits of statin therapy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Circadian rhythms underlie many immune responses and allergic diseases. Subcutaneous immunotherapy (SCIT) can result in adverse reactions; however, it is unclear whether such reactions have a diurnal pattern., Objective: To assess whether the timing of SCIT affects the rate of adverse reactions., Methods: This study was a retrospective medical record review of adult patients (n = 289) who received SCIT at the Northwestern Medical Faculty Foundation, Chicago, Illinois, during a 10-year period (2004-2014). Injections were given in the outpatient setting. There were a total of 17,457 injections with 574 reactions. Covariates included age, sex, median income, asthma status, vial contents, number of injections, and previous immunotherapy reactions. Logistical regression was used to calculate the odds of having a reaction with time of SCIT administration as the primary determinate., Results: Immunotherapy reactions occurred more frequently after afternoon or evening (pm) injections (328/8721 = 3.8%) vs morning (am) injections (246/8736 = 2.8%), (χ 2  = 12.26, P < .01). Systemic reactions, defined as World Allergy Organization grade 1 or higher, did not have diurnal variation (59/8721 = 0.67% for pm vs am 56/8736 = 0.64% for morning; χ 2  = 0.08; P = .77). pm injections resulted in higher odds of reaction compared with am injection in a fully adjusted logistic regression model (odds ratio = 1.43; 95% confidence interval, 1.20-1.70; P < .01). When considering time as 4 categories, the highest odds of reaction were noted for the period from 15:01 to 17:30 (odds ratio, 1.55; 95% confidence interval, 1.21-2.00; P < .01)., Conclusion: pm injections of SCIT are associated with increased cutaneous reaction rates when compared with am injections. In patients experiencing bothersome local reactions, it may be beneficial to administer SCIT in the morning., (Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Children with atopic dermatitis (AD) experience significant sleep disruption, and clinically, the disease is noted to worsen in a circadian manner at night. Epidemiologic findings highlight many negative consequences of AD, such as impaired linear growth, which is uniquely related to disturbed sleep. Clinical guidelines currently recommend assessing sleep in patients with AD as a crucial parameter of disease control with appropriate treatment. In this review we describe our current understanding of the roles of sleep cycles and circadian rhythms in the nighttime exacerbation of AD (nocturnal eczema). We present a schematic to explain the mechanism of nocturnal eczema. Treatment options for sleep disturbance and future directions for research are discussed in the context of AD., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)