Publications by authors named "Richard Wunderink"

Identifying immunosuppressed patients using structured data can be challenging. Large language models effectively extract structured concepts from unstructured clinical text. Here we show that GPT-4o outperforms traditional approaches in identifying immunosuppressive conditions and medication use by processing hospital admission notes.

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Background: Serotype-specific urinary antigen detection (UAD) assay results can be used to estimate the serotype contribution among adults with pneumococcal community-acquired pneumonia (CAP) and to guide recommendations regarding higher-valency pneumococcal conjugate vaccines (PCVs).

Methods: Adults aged ≥18 years hospitalized with radiographic evidence of CAP were prospectively enrolled in 4 US cities from November 2019 to December 2020, overlapping the coronavirus disease 2019 (COVID-19) pandemic. Data were collected by patient interview and medical chart review.

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Article Synopsis
  • - The EPIC study analyzed data from 2,272 adults hospitalized for pneumonia to understand the prevalence of Mycoplasma pneumoniae (Mp) using PCR testing on throat swabs from 2010 to 2012.
  • - Only 43 patients (1.8%) tested positive for Mp, primarily affecting younger adults (median age: 45), with some experiencing severe cases leading to ICU admissions, but no in-hospital deaths were reported.
  • - Factors linked to higher Mp detection included being younger and having certain radiographic findings, indicating the need for better testing methods to improve diagnosis and treatment options for pneumonia patients.
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Background: Antibiotic stewardship in critically ill pneumonia patients is crucial yet challenging, partly due to the limited diagnostic yield of noninvasive infectious tests. In this study, we report an antibiotic prescription pattern informed by bronchoalveolar lavage (BAL) results, where clinicians de-escalate antibiotics based on the combination of quantitative cultures and multiplex PCR rapid diagnostic tests.

Methods: We analyzed data from SCRIPT, a single-center prospective cohort study of mechanically ventilated patients who underwent a BAL for suspected pneumonia.

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A leading cause of mortality after influenza infection is the development of a secondary bacterial pneumonia. In the absence of a bacterial superinfection, prescribing antibacterial therapies is not indicated but has become a common clinical practice for those presenting with a respiratory viral illness. In a murine model, we found that antibiotic use during influenza infection impaired the lung innate immunologic defenses toward a secondary challenge with methicillin-resistant Staphylococcus aureus (MRSA).

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Article Synopsis
  • - The study focused on the impact of an evidence-based sedation bundle for ICU patients requiring mechanical ventilation during the early phase of the COVID-19 pandemic, addressing the challenges posed by increased patient volumes.
  • - Researchers implemented the sedation bundle using structured training and feedback, aiming to encourage goal-directed sedation to prevent excessive use of sedatives among critically ill COVID-19 patients.
  • - A comparison of sedative use and clinical outcomes was made between patients admitted before and after the bundle implementation, revealing increased use of benzodiazepines and changes in patient care metrics.
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is a common nosocomial pathogen and a major cause of morbidity and mortality in hospitalized patients. Multiple reports highlight that gastrointestinal colonization may precede systemic infections by this pathogen. Gaining a deeper insight into the dynamics of gastrointestinal carriage is an essential step in managing gastrointestinal colonization and could contribute to preventing bacterial transmission and progression to systemic infection.

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The precise microbial determinants driving clinical outcomes in severe pneumonia are unknown. Competing ecological forces produce dynamic microbiota states in health; infection and treatment effects on microbiota state must be defined to improve pneumonia therapy. Here, we leverage our unique clinical setting, which includes systematic and serial bronchoscopic sampling in patients with suspected pneumonia, to determine lung microbial ecosystem dynamics throughout pneumonia therapy.

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The evolution of T cell molecular signatures in the distal lung of patients with severe pneumonia is understudied. Here, we analyzed T cell subsets in longitudinal bronchoalveolar lavage fluid samples from 273 patients with severe pneumonia, including unvaccinated patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or with respiratory failure not linked to pneumonia. In patients with SARS-CoV-2 pneumonia, activation of interferon signaling pathways, low activation of the NF-κB pathway and preferential targeting of spike and nucleocapsid proteins early after intubation were associated with favorable outcomes, whereas loss of interferon signaling, activation of NF-κB-driven programs and specificity for the ORF1ab complex late in disease were associated with mortality.

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Continued improvements in the treatment of pulmonary infections have paradoxically resulted in a growing challenge of individuals with postinfectious pulmonary complications (PIPCs). PIPCs have been long recognized after tuberculosis, but recent experiences such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have underscored the importance of PIPCs following other lower respiratory tract infections. Independent of the causative pathogen, most available studies of pulmonary infections focus on short-term outcomes rather than long-term morbidity among survivors.

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Introduction: The rapid development of artificial intelligence (AI) in healthcare has exposed the unmet need for growing a multidisciplinary workforce that can collaborate effectively in the learning health systems. Maximizing the synergy among multiple teams is critical for Collaborative AI in Healthcare.

Methods: We have developed a series of data, tools, and educational resources for cultivating the next generation of multidisciplinary workforce for Collaborative AI in Healthcare.

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Introduction: In patients with suspected pneumonia who are tested with respiratory culture and multiplex PCR, the potential added benefit of next-generation sequencing technologies is unknown.

Methods: This was a single-center, retrospective study in which residual bronchoalveolar lavage (BAL) specimens were retrieved from hospitalized patients. We compared its research-use-only Respiratory Pathogen Illumina Panel (RPIP) results to culture and BioFire FilmArray Pneumonia Panel (BioFire PN) results from critically ill patients.

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Rationale: Pneumonia is the most common infection in ICU patients and a leading cause for death. Assessment of bronchoalveolar lavage fluid (BALF) cellularity can aid in pneumonia diagnosis. Low percentages (<50%) of BALF neutrophils have a high negative predictive value for bacterial pneumonia in a general medical ICU population.

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Evidence suggests system-level norms and care processes influence individual patients' medical decisions, including end-of-life decisions for patients with critical illnesses like acute respiratory failure. Yet, little is known about how these processes unfold over the course of a patient's critical illness in the intensive care unit (ICU). Our objective was to map current-state ICU care delivery processes for patients with acute respiratory failure and to identify opportunities to improve the process.

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BACKGROUNDSurvivors of pneumonia, including SARS-CoV-2 pneumonia, are at increased risk for cognitive dysfunction and dementia. In rodent models, cognitive dysfunction following pneumonia has been linked to the systemic release of lung-derived pro-inflammatory cytokines. Microglia are poised to respond to inflammatory signals from the circulation, and their dysfunction has been linked to cognitive impairment in murine models of dementia and in humans.

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Rationale: Critically ill patients who develop invasive pulmonary aspergillosis (IPA) have high mortality rates despite antifungal therapy. Diagnosis is difficult in these patients. Bronchoalveolar lavage (BAL) fluid galactomannan (GM) is a helpful marker of infection, although the optimal cutoff for IPA is unclear.

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There are several novel platforms that enhance detection of pathogens that cause common infections in the intensive care unit. These platforms have a sample to answer time of a few hours, are often higher yield than culture, and have the potential to improve antibiotic stewardship.

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The microbiology of severe community acquired pneumonia (SCAP) has implications on management, clinical outcomes and public health policy. Therefore, knowledge of the etiologies of SCAP and methods to identify these microorganisms is key. Bacteria including Streptococcus pneumoniae, Staphylococcus aureus and Enterobacteriaceae continue to be important causes of SCAP.

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Pathogen clearance and resolution of inflammation in patients with pneumonia require an effective local T cell response. Nevertheless, local T cell activation may drive lung injury, particularly during prolonged episodes of respiratory failure characteristic of severe SARS-CoV-2 pneumonia. While T cell responses in the peripheral blood are well described, the evolution of T cell phenotypes and molecular signatures in the distal lung of patients with severe pneumonia caused by SARS-CoV-2 or other pathogens is understudied.

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It is unclear whether plasma is a reliable surrogate for target attainment in the epithelial lining fluid (ELF). The objective of this study was to characterize meropenem target attainment in plasma and ELF using prospective samples. The first 24-hour T was evaluated vs 1xMIC and 4xMIC targets at the patient (i.

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Neurological impairment is the most common finding in patients with post-acute sequelae of COVID-19. Furthermore, survivors of pneumonia from any cause have an elevated risk of dementia. Dysfunction in microglia, the primary immune cell in the brain, has been linked to cognitive impairment in murine models of dementia and in humans.

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Background: Clinical end points that constitute successful treatment in severe pneumonia are difficult to ascertain and vulnerable to bias. The utility of a protocolized adjudication procedure to determine meaningful end points in severe pneumonia has not been well described.

Methods: This was a single-center prospective cohort study of patients with severe pneumonia admitted to the medical intensive care unit.

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