Validation of a Host Response Assay, SeptiCyte LAB, for Discriminating Sepsis from Systemic Inflammatory Response Syndrome in the ICU.

RATIONALE: A molecular test to distinguish between sepsis and systemic inflammation of noninfectious etiology could potentially have clinical utility. OBJECTIVES: This study evaluated the diagnostic performance of a molecular host response assay (SeptiCyte LAB) designed to distinguish between sepsis and noninfectious systemic inflammation in critically ill adults. METHODS: The study employed a prospective, observational, noninterventional design and recruited a heterogeneous cohort of adult critical care patients from seven sites in the United States (n = 249). An additional group of 198 patients, recruited in the large MARS (Molecular Diagnosis and Risk Stratification of Sepsis) consortium trial in the Netherlands ( www.clinicaltrials.gov identifier NCT01905033), was also tested and analyzed, making a grand total of 447 patients in our study. The performance of SeptiCyte LAB was compared with retrospective physician diagnosis by a panel of three experts. MEASUREMENTS AND MAIN RESULTS: In receiver operating characteristic curve analysis, SeptiCyte LAB had an estimated area under the curve of 0.82-0.89 for discriminating sepsis from noninfectious systemic inflammation. The relative likelihood of sepsis versus noninfectious systemic inflammation was found to increase with increasing test score (range, 0-10). In a forward logistic regression analysis, the diagnostic performance of the assay was improved only marginally when used in combination with other clinical and laboratory variables, including procalcitonin. The performance of the assay was not significantly affected by demographic variables, including age, sex, or race/ethnicity. CONCLUSIONS: SeptiCyte LAB appears to be a promising diagnostic tool to complement physician assessment of infection likelihood in critically ill adult patients with systemic inflammation. Clinical trial registered with www.clinicaltrials.gov (NCT01905033 and NCT02127502).

Randomized Open Investigation Determining Steroid Dose in Severe COVID-19: The ROIDS-Dose Clinical Trial.

Introduction Treatment with dexamethasone reduces mortality in patients with coronavirus disease 2019 (COVID-19) pneumonia requiring supplemental oxygen, but the optimal dose has not been determined. Objective To determine whether weight-based dexamethasone of 0.2 mg/kg is superior to 6 mg daily in reducing 28-day mortality in patients with COVID-19 and hypoxemia. Materials and methods A multicenter, open-label, randomized clinical trial was conducted between March 2021 and December 2021 at seven hospitals within Northwell Health. A total of 142 patients with confirmed COVID-19 and hypoxemia were included. Participants were randomized in a 1:1 ratio to dexamethasone 0.2 mg/kg intravenously daily (n = 70) or 6 mg daily (n = 72) for up to 10 days. Results There was no statistically significant difference in the primary outcome of 28-day all-cause mortality with deaths in 12 of 70 patients (17.14%) in the intervention group and 15 of 72 patients (20.83%) in the control group (p = 0.58). There were no statistically significant differences among the secondary outcomes. Conclusion In patients with COVID-19 and hypoxemia, the use of weight-based dexamethasone dosing was not superior to dexamethasone 6 mg in reducing all-cause mortality at 28 days. Clinical trial registration This study was registered under ClinicalTrials.gov (identifier: NCT04834375).

Rapid Eye Movement Behavior Disorder and Other Parasomnias.

Rapid eye movement (REM) behavior disorder (RBD) is characterized by loss of skeletal muscle atonia that can lead to dream enactment. This condition can cause harm to patients and their bed partners if appropriate safety measures are not ensured. This condition is often the initial presenting symptom in a group of complex neurodegenerative processes. Definitive diagnosis requires a thorough history and an in-laboratory polysomnogram to look for evidence of REM sleep without atonia. Treatment options are limited but consist of sleep safety measures and pharmacotherapy. Patients diagnosed with idiopathic RBD associated with alpha-synucleinopathy are likely to have progression of disease.

Space invader: pleural penetration of a hypoglossal nerve stimulator sensor lead.

The mainstay of treatment for obstructive sleep apnea is positive airway pressure therapy, which may be difficult for some patients to tolerate leading to compromised adherence and requiring alternative therapies. Hypoglossal nerve stimulation has become an option for those who meet implantation criteria. Implantation of the device is an ambulatory surgical procedure and is generally well-tolerated, though rare adverse events have been reported. We report an unusual complication of hypoglossal nerve stimulation in a patient who had initial success with this therapy. After 3 years of treatment, the sensor lead penetrated into the pleural space. Components of the hypoglossal nerve stimulation were explanted, and a new sensor lead and generator were reimplanted. The new device was activated, and therapy was successfully resumed. This case demonstrates that there is a potential for a delayed complication of sensor lead penetration into the pleural space, which has only rarely been reported. CITATION: Lou B, Hahn S, Korotun M, Quintero L, Shikowitz M, Greenberg H. Space invader: pleural penetration of a hypoglossal nerve stimulator sensor lead. J Clin Sleep Med. 2021;17(11):2329-2332.

Effective use of monoclonal antibodies for treatment of persistent COVID-19 infection in a patient on rituximab.

As we are over a year into the COVID-19 pandemic, we have made many forward strides in therapeutics. These treatments, such as monoclonal antibodies, have help mitigate the detrimental and often fatal consequences of COVID-19. The current indication for the use of monoclonal antibodies is mild to moderate COVID-19 infection within 10 days of symptom onset in those who are at high risk of progression to severe disease. However, their role in patients with prolonged symptoms is not clear. We present a unique case of monoclonal antibodies use after 54 days of symptom onset in an immunosuppressed patient with persistent COVID-19 infection despite standard treatment. This case illustrates the potential use of monoclonal antibodies outside of the current recommended therapeutic window in immunosuppressed patients, who may have difficulty with viral clearance.

Pneumothorax in COVID-19 Acute Respiratory Distress Syndrome: Case Series.

Objective The study aims to describe the clinical characteristics and outcomes of patients with COVID-19 related acute respiratory distress syndrome (ARDS) who developed pneumothorax. Design and setting A retrospective chart review was performed of the electronic medical record. Patients were included if they were identified as having confirmed COVID-19 as well as pneumothorax from March 16, 2020 to May 31, 2020. Patients' demographic and clinical characteristics, mechanical ventilator parameters, lung compliance measurements and outcomes during hospitalization were collected. This case series was conducted in intensive care units at two large tertiary care centers within the Northwell Health System, located in New York State. Patients A total of 75 patients were identified who were predominantly male (73.3%) with an average age of 62.8 years. Thirty (40%) were Hispanic, 20 (26.7%) were White, 16 (21.3%) were Asian, and nine (12%) were Black. Common comorbid conditions were hypertension (52%), diabetes mellitus (26.7%), hyperlipidemia (32.0%), and chronic pulmonary disease (8, 10.7%). Measurements and main results Most of the patients were diagnosed with pneumothorax while on mechanical ventilation (92%) despite overall adherence with lung-protective ventilation strategies. Average tidal volume was 6.66 mL/kg) of ideal body weight. The average positive end-expiratory pressure (PEEP) was 10.83 (cm) H2O. Lung compliance was poor, with average peak and plateau pressures of 41.9 cm H2O and 35.2 cm H2O, respectively. Inpatient mortality was high in these patients (76%). Conservative management with initial observation had a success rate (73.3%) with similar mortality and shorter length of stay (LOS) on average. Significant factors in the conservatively managed group included lack of tension physiology, the smaller size of pneumothorax, lack of underlying diabetes, presence of pneumomediastinum, and not being on mechanical ventilation during diagnosis. Conclusion Despite overall adherence to best practice ventilator management in ARDS, we observed a large number of pneumothoraces during the COVID-19 pandemic. Conservative management may be appropriate if there are no clinical signs or symptoms of tension physiology and pneumothorax size is small.

Physician agreement on the diagnosis of sepsis in the intensive care unit: estimation of concordance and analysis of underlying factors in a multicenter cohort.

BACKGROUND: Differentiating sepsis from the systemic inflammatory response syndrome (SIRS) in critical care patients is challenging, especially before serious organ damage is evident, and with variable clinical presentations of patients and variable training and experience of attending physicians. Our objective was to describe and quantify physician agreement in diagnosing SIRS or sepsis in critical care patients as a function of available clinical information, infection site, and hospital setting. METHODS: We conducted a post hoc analysis of previously collected data from a prospective, observational trial (N = 249 subjects) in intensive care units at seven US hospitals, in which physicians at different stages of patient care were asked to make diagnostic calls of either SIRS, sepsis, or indeterminate, based on varying amounts of available clinical information (clinicaltrials.gov identifier: NCT02127502). The overall percent agreement and the free-marginal, inter-observer agreement statistic kappa (κ free) were used to quantify agreement between evaluators (attending physicians, site investigators, external expert panelists). Logistic regression and machine learning techniques were used to search for significant variables that could explain heterogeneity within the indeterminate and SIRS patient subgroups. RESULTS: Free-marginal kappa decreased between the initial impression of the attending physician and (1) the initial impression of the site investigator (κ free 0.68), (2) the consensus discharge diagnosis of the site investigators (κ free 0.62), and (3) the consensus diagnosis of the external expert panel (κ free 0.58). In contrast, agreement was greatest between the consensus discharge impression of site investigators and the consensus diagnosis of the external expert panel (κ free 0.79). When stratified by infection site, κ free for agreement between initial and later diagnoses had a mean value + 0.24 (range - 0.29 to + 0.39) for respiratory infections, compared to + 0.70 (range + 0.42 to + 0.88) for abdominal + urinary + other infections. Bioinformatics analysis failed to clearly resolve the indeterminate diagnoses and also failed to explain why 60% of SIRS patients were treated with antibiotics. CONCLUSIONS: Considerable uncertainty surrounds the differential clinical diagnosis of sepsis vs. SIRS, especially before organ damage has become highly evident, and for patients presenting with respiratory clinical signs. Our findings underscore the need to provide physicians with accurate, timely diagnostic information in evaluating possible sepsis.

Early in-hospital clinical deterioration is not predicted by severity of illness, functional status, or comorbidity.

BACKGROUND: Prior studies concentrated on unplanned intensive care unit (ICU) transfer to gauge deterioration occurring shortly following hospital admission. However, examining only ICU transfers is not ideal since patients could stabilize with treatment, refuse ICU admission, or not require ICU evaluation. To further explore etiologies of early clinical deterioration, we used rapid response team (RRT) activation within 48 hours of admission as an index of early clinical worsening. METHODS: A retrospective analysis of prospectively gathered admissions from the emergency department in an academic medical center was done. Data were reviewed independently by two physicians. We assessed severity of illness, functional status, comorbidity, the frequency of ICU and palliative care consultations, and changes in advance health care directives. RESULTS: Of 655 rapid responses (RRs) within the study period, 24.6% occurred within 48 hours of admission. Disease trajectory was the most frequent perceived reason for RRs (55.6% and 58.9%, reviewer 1 and 2, respectively) followed by medical error (15.6% and 15.2%). Acute physiology and chronic health evaluation II (APACHE-II) and modified early warning scores (MEWS) were higher at the time of RR compared to admission (p<0.0001). However, admission APACHE-II, MEWS, functional status, and comorbidity scores did not predict early RRs. One third of RRs resulted in ICU consultation and 95% were accepted. Palliative care consults were requested for 15%, the majority (65%) after RR and all resulting in advance directive change. CONCLUSION: Disease trajectory accounted for most clinical deterioration and medical error contributed to 15%. Our data suggest that it is difficult to predict early clinical deterioration as none of the measured parameters were associated with RRT activation.

A review of therapeutic agents for the management of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is an uncommon, progressive and life threatening disease characterized by a proliferative vasculopathy of the small muscular pulmonary arterioles resulting in elevated pulmonary vascular resistance and eventually right ventricular failure. An increasing understanding of the pathobiology of PAH and its natural history has led to the development of numerous targeted therapies. Despite these advances there is significant progression of disease and the survival rate remains low. This article reviews the agents currently available for the medical management of PAH.