Cell-Free DNA Maps Tissue Injury and Correlates with Disease Severity in Lung Transplant Candidates.

Rationale: Plasma cell-free DNA levels correlate with disease severity in many conditions. Pretransplant cell-free DNA may risk stratify lung transplant candidates for post-transplant complications. Objectives: To evaluate if pretransplant cell-free DNA levels and tissue sources identify patients at high risk of primary graft dysfunction and other pre- and post-transplant outcomes. Methods: This multicenter, prospective cohort study recruited 186 lung transplant candidates. Pretransplant plasma samples were collected to measure cell-free DNA. Bisulfite sequencing was performed to identify the tissue sources of cell-free DNA. Multivariable regression models determined the association between cell-free DNA levels and the primary outcome of primary graft dysfunction and other transplant outcomes, including Lung Allocation Score, chronic lung allograft dysfunction, and death. Measurements and Main Results: Transplant candidates had twofold greater cell-free DNA levels than healthy control patients (median [interquartile range], 23.7 ng/ml [15.1-35.6] vs. 12.9 ng/ml [9.9-18.4]; P < 0.0001), primarily originating from inflammatory innate immune cells. Cell-free DNA levels and tissue sources differed by native lung disease category and correlated with the Lung Allocation Score (P < 0.001). High pretransplant cell-free DNA increased the risk of primary graft dysfunction (odds ratio, 1.60; 95% confidence interval [CI], 1.09-2.46; P = 0.0220), and death (hazard ratio, 1.43; 95% CI, 1.07-1.92; P = 0.0171) but not chronic lung allograft dysfunction (hazard ratio, 1.37; 95% CI, 0.97-1.94; P = 0.0767). Conclusions: Lung transplant candidates demonstrate a heightened degree of tissue injury with elevated cell-free DNA, primarily originating from innate immune cells. Pretransplant plasma cell-free DNA levels predict post-transplant complications.

Peri-Ictal Changes in Depression and Anxiety in Persons With Epileptic and Non-epileptic Seizures.

Objective: We tested the hypothesis that epileptic, but not non-epileptic, seizures would produce an improvement in comorbid depression and anxiety symptoms in the peri-ictal period, much like the antidepressant effects of electroconvulsive therapy. Methods: We examined depression and anxiety symptoms in patients admitted to an inpatient unit for continuous video electroencephalography as part of routine clinical care. Patients completed three questionnaires that included the Beck Depression Inventory-II (BDI), Montgomery Asberg Depression Rating Scale (MADRS), and Beck Anxiety Inventory (BAI) after admission, in the 24 h following a seizure, then again 2 weeks after the last seizure. Results: In patients with epilepsy, depression and anxiety scores improved in the 24 hrs following a seizure (change in BDI = 24%; change in MADRS = 19%; change in BAI = 21%) but returned toward baseline after 2 weeks. In patients with non-epileptic seizures, depression and anxiety scores also improved in the 24 hrs following a psychogenic non-epileptic seizure (change in BDI = 17%, change in MADRS = 27%, change in BAI = 36%). There was a greater improvement in depression and anxiety scores in patients with focal-onset epilepsy (BDI = 30%, MADRS = 22%, BAI = 30%) compared to generalized seizure onset (BDI = 6%, MADRS = 12%, BAI = 8%). Conclusion: We conclude that single seizures can result in transient improvements in mood. Because seizures need not be generalized or epileptic to exert this effect, the underlying mechanisms are uncertain.

A qualitative assessment of the diagnosis and management of ventilator-associated pneumonia among critical care clinicians exploring opportunities for diagnostic stewardship.

BACKGROUND: Prompt diagnosis and intervention for ventilator-associated pneumonia (VAP) is critical but can lead to overdiagnosis and overtreatment. OBJECTIVES: We investigated healthcare provider (HCP) perceptions and challenges associated with VAP diagnosis, and we sought to identify opportunities for diagnostic stewardship. METHODS: We conducted a qualitative study of 30 HCPs at a tertiary-care hospital. Participants included attending physicians, residents and fellows (trainees), advanced practice providers (APPs), and pharmacists. Interviews were composed of open-ended questions in 4 sections: (1) clinical suspicion and thresholds for respiratory culture ordering, (2) preferences for respiratory sample collection, (3) culture report interpretation, and (4) VAP diagnosis and treatment. Interviews transcripts were analyzed using Nvivo 12 software, and responses were organized into themes. RESULTS: Overall, 10 attending physicians (75%) and 16 trainees (75%) trainees and APPs believed they were overdiagnosing VAP; this response was frequent among HCPs in practice 5-10 years (91%, n = 12). Increased identification of bacteria as a result of frequent respiratory culturing, misinterpretation of culture data, and fear of missing diagnosis were recognized as drivers of overdiagnosis and overtreatment. Although most HCPs rely on clinical and radiographic changes to initiate work-up, the fear of missing a diagnosis leads to sending cultures even in the absence of those changes. CONCLUSIONS: HCPs believe that VAP overdiagnosis and overtreatment are common due to fear of missing diagnosis, overculturing, and difficulty distinguishing colonization from infection. Although we identified opportunities for diagnostic stewardship, interventions influencing the ordering of cultures and starting antimicrobials will need to account for strongly held beliefs and ICU practices.

A Survey of Academic Intensivists' Use of Neuromuscular Blockade in Subjects With ARDS.

BACKGROUND: Our Cooling to Help Injured Lungs (CHILL) trial of therapeutic hypothermia in ARDS includes neuromuscular blockade (NMB) as an inclusion criterion to avoid shivering. NMB has been used to facilitate mechanical ventilation in ARDS and was shown to reduce mortality in the ACURASYS trial. To assess the feasibility of a multi-center CHILL trial, we conducted a survey of academic intensivists about their NMB use in patients with ARDS. METHODS: We distributed via email a 16-question survey about NMB use in patients with ARDS including frequency, indications, and dosing strategy. RESULTS: 212 (24.3%) of 871 respondents completed the survey: 94.7% were board-certified in internal medicine, 88% in pulmonary and critical care; 90.3% practiced in academic medical centers, with 87% working in medical ICUs; 96.6% of respondents who treat ARDS use NMB, and 39.7% use NMB in ≥ 50% of these patients. Of 4 listed indications for initiating NMB in ARDS, allowing adherence with lung-protective ventilator strategies and patient-ventilator synchrony were cited as the most important reasons, followed by the results of the ACURASYS trial and facilitating prone positioning. CONCLUSIONS: We conclude that NMB is frequently used by academic intensivists to facilitate mechanical ventilation in patients with moderate to severe ARDS.

Ventilator-Associated Pneumonia: Diagnostic Test Stewardship and Relevance of Culturing Practices.

PURPOSE OF REVIEW: Ventilator-associated pneumonia (VAP) is one of the most common infections in the ICU. Prompt diagnosis is vital as mortality increases with delayed antibiotic therapy. However, accurate diagnosis is challenging due to non-specific clinical features in a complicated patient cohort. Microbiological culture data remains a crucial aspect in confirming diagnosis. RECENT FINDINGS: Literature data comparing the benefit of invasive respiratory sampling to non-invasive is inconclusive. Differences in culturing practices translate in overidentification of organisms of unclear significance. Positive culture data in a low pre-test probability does not differentiate between true infection and colonization resulting in overtreatment. Furthermore, there are also opportunities for modifying the reporting of respiratory tract cultures that can better guide antimicrobial therapy. Under the umbrella of antimicrobial stewardship, diagnostic stewardship can be incorporated to create a systematic approach that would target culturing practices to match the right pre-test probability. Ideal outcome will be targeting cultures to the right patient population and minimizing unnecessary treatment.

A Case of Bartonella Quintana Culture-Negative Endocarditis.

BACKGROUND Culture-negative Bartonella quintana endocarditis is challenging to diagnose and is associated with high mortality rates. Diagnostic confirmation of Bartonella quintana infection requires specialized assays, as identifying Bartonella henselae endocarditis by serology can be difficult due to the high rate of serological cross-reactivity. This is a case report of culture-negative Bartonella quintana endocarditis that was diagnosed with epidemiologic data, histology, and nucleic acid amplification testing. CASE REPORT A 28-year-old man with a history of homelessness was admitted to hospital with worsening productive cough, weight loss, and abdominal pain. A transthoracic echocardiogram (TTE) showed pulmonary valve vegetation and several aortic valve vegetations. His hospital course was complicated by cardiogenic shock and septic shock requiring transfer to a tertiary care medical intensive care unit. Although blood cultures remained negative for bacterial infection, serology testing was positive for Bartonella henselae and Bartonella quintana IgM and IgG. Nucleic acid amplification testing for 16S ribosomal RNA (rRNA) using valve tissue was diagnostic for Bartonella quintana. CONCLUSIONS This case of culture-negative Bartonella quintana endocarditis demonstrates the use of diagnostic nucleic acid amplification methods to confirm the diagnosis.

Acute Transverse Myelitis Associated with Salmonella Bacteremia: A Case Report.

BACKGROUND Acute transverse myelitis (ATM) is an uncommon and often overlooked complication of certain bacterial and viral infections that can have a rapid onset and result in severe neurological deficits.  CASE REPORT This case report describes a previously healthy 28-year-old woman who presented to the trauma center after developing acute paralysis and paresthesias of all four extremities within the span of hours. The initial presumptive diagnosis was spinal cord contusion due to a fall versus an unknown mechanism of trauma, but eventual laboratory studies revealed Salmonella bacteremia, indicating a probable diagnosis of parainfectious ATM. CONCLUSIONS This case illustrates the importance of considering the diagnosis of parainfectious ATM in patients presenting with acute paralysis with incomplete or unobtainable medical histories.