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1.
Nat Immunol ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138384

RESUMO

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. These results suggest that in patients with severe SARS-CoV-2 pneumonia, alveolar T cell interferon responses targeting structural SARS-CoV-2 proteins characterize individuals who recover, whereas responses against nonstructural proteins and activation of NF-κB are associated with poor outcomes.

2.
Nature ; 602(7896): 321-327, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34937051

RESUMO

It is not fully understood why COVID-19 is typically milder in children1-3. Here, to examine the differences between children and adults in their response to SARS-CoV-2 infection, we analysed paediatric and adult patients with COVID-19 as well as healthy control individuals (total n = 93) using single-cell multi-omic profiling of matched nasal, tracheal, bronchial and blood samples. In the airways of healthy paediatric individuals, we observed cells that were already in an interferon-activated state, which after SARS-CoV-2 infection was further induced especially in airway immune cells. We postulate that higher paediatric innate interferon responses restrict viral replication and disease progression. The systemic response in children was characterized by increases in naive lymphocytes and a depletion of natural killer cells, whereas, in adults, cytotoxic T cells and interferon-stimulated subpopulations were significantly increased. We provide evidence that dendritic cells initiate interferon signalling in early infection, and identify epithelial cell states associated with COVID-19 and age. Our matching nasal and blood data show a strong interferon response in the airways with the induction of systemic interferon-stimulated populations, which were substantially reduced in paediatric patients. Together, we provide several mechanisms that explain the milder clinical syndrome observed in children.


Assuntos
COVID-19/sangue , COVID-19/imunologia , Células Dendríticas/imunologia , Interferons/imunologia , Células Matadoras Naturais/imunologia , SARS-CoV-2/imunologia , Linfócitos T Citotóxicos/imunologia , Adulto , Brônquios/imunologia , Brônquios/virologia , COVID-19/patologia , Chicago , Estudos de Coortes , Progressão da Doença , Células Epiteliais/citologia , Células Epiteliais/imunologia , Células Epiteliais/virologia , Feminino , Humanos , Imunidade Inata , Londres , Masculino , Mucosa Nasal/imunologia , Mucosa Nasal/virologia , SARS-CoV-2/crescimento & desenvolvimento , Análise de Célula Única , Traqueia/virologia , Adulto Jovem
3.
Semin Respir Crit Care Med ; 45(2): 158-168, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38196061

RESUMO

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. Viruses remain the most commonly identified etiology of SCAP. Atypical organisms are also important etiologies of SCAP and are critical to identify for public health. With the increased number of immunocompromised individuals, less common pathogens may also be found as the causative agent of SCAP. Traditional diagnostic tests, including semi-quantitative respiratory cultures, blood cultures and urinary antigens continue to hold an important role in the evaluation of patients with SCAP. Many of the limitations of the aforementioned tests are addressed by rapid, molecular diagnostic tests. Molecular diagnostics utilize culture-independent technology to identify species-specific genetic sequences. These tests are often semi-automated and provide results within hours, which provides an opportunity for expedient antibiotic stewardship. The existing literature suggests molecular diagnostic techniques may improve antibiotic stewardship in CAP, and future research should investigate optimal methods for implementation of these assays into clinical practice.


Assuntos
Infecções Comunitárias Adquiridas , Pneumonia , Vírus , Humanos , Pneumonia/diagnóstico , Pneumonia/microbiologia , Streptococcus pneumoniae , Enterobacteriaceae , Staphylococcus aureus , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/microbiologia
4.
Am J Respir Crit Care Med ; 207(5): 566-576, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36095143

RESUMO

Rationale: Obesity affects 40% of U.S. adults, is associated with a proinflammatory state, and presents a significant risk factor for the development of severe coronavirus disease (COVID-19). To date, there is limited information on how obesity might affect immune cell responses in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objectives: To determine the impact of obesity on respiratory tract immunity in COVID-19 across the human lifespan. Methods: We analyzed single-cell transcriptomes from BAL in three ventilated adult cohorts with (n = 24) or without (n = 9) COVID-19 from nasal immune cells in children with (n = 14) or without (n = 19) COVID-19, and from peripheral blood mononuclear cells in an independent adult COVID-19 cohort (n = 42), comparing obese and nonobese subjects. Measurements and Main Results: Surprisingly, we found that obese adult subjects had attenuated lung immune or inflammatory responses in SARS-CoV-2 infection, with decreased expression of IFN-α, IFN-γ, and TNF-α (tumor necrosis factor α) response gene signatures in almost all lung epithelial and immune cell subsets, and lower expression of IFNG and TNF in specific lung immune cells. Peripheral blood immune cells in an independent adult cohort showed a similar but less marked reduction in type-I IFN and IFNγ response genes, as well as decreased serum IFNα, in obese patients with SARS-CoV-2. Nasal immune cells from obese children with COVID-19 also showed reduced enrichment of IFN-α and IFN-γ response genes. Conclusions: These findings show blunted tissue immune responses in obese patients with COVID-19, with implications for treatment stratification, supporting the specific application of inhaled recombinant type-I IFNs in this vulnerable subset.


Assuntos
COVID-19 , Interferon Tipo I , Obesidade Infantil , Adulto , Humanos , Criança , SARS-CoV-2 , Leucócitos Mononucleares , Pulmão/patologia
5.
Semin Respir Crit Care Med ; 44(1): 8-20, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36646082

RESUMO

Community-acquired pneumonia (CAP) is a significant cause of morbidity and mortality, one of the most common reasons for infection-related death worldwide. Causes of CAP include numerous viral, bacterial, and fungal pathogens, though frequently no specific organism is found. Beginning in 2019, the COVID-19 pandemic has caused incredible morbidity and mortality. COVID-19 has many features typical of CAP such as fever, respiratory distress, and cough, and can be difficult to distinguish from other types of CAP. Here, we highlight unique clinical features of COVID-19 pneumonia such as olfactory and gustatory dysfunction, lymphopenia, and distinct imaging appearance.


Assuntos
COVID-19 , Infecções Comunitárias Adquiridas , Pneumonia Bacteriana , Humanos , COVID-19/complicações , Pneumonia Bacteriana/epidemiologia , Pandemias , Infecções Comunitárias Adquiridas/epidemiologia
6.
J Gen Intern Med ; 37(9): 2251-2258, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35710669

RESUMO

BACKGROUND: Animation in medical education has boomed over the past two decades, and demand for distance learning technologies will likely continue in the context of the COVID-19 pandemic. However, experimental data guiding best practices for animation in medical education are scarce. OBJECTIVE: To compare the efficacy of two animated video styles in a diabetes pharmacotherapy curriculum for internal medicine residents. DESIGN: Learners were randomized to receive one of two versions of the same multimodal didactic curriculum. They received identical lectures, group activities, and quizzes, but were randomized to either digital chalk talk (DCT) videos or Sugar-Coated Science (SCS). SCS is an animated series using anthropomorphic characters, stories, and mnemonics to communicate knowledge. PARTICIPANTS: Ninety-two internal medicine residents at a single academic medical center received the curriculum within ambulatory medicine didactics. MAIN MEASURES: Knowledge was measured at multiple time points, as was residents' self-reported comfort using each medication class covered. Surveys assessed video acceptability and telepresence. Key themes were identified from open-ended feedback. KEY RESULTS: Baseline knowledge was low, consistent with prior needs assessments. On immediate posttest, mean scores were higher with SCS than DCT (74.8% versus 68.4%), but the difference was not statistically significant, p = 0.10. Subgroup analyses revealed increased knowledge in the SCS group for specific medication classes. Delayed posttest showed significant knowledge gains averaging 17.6% across all participants (p < 0.05); these gains were similar between animation types. SCS achieved significantly higher telepresence, entertainment, and acceptability scores than DCT. Qualitative data suggested that residents prioritize well-designed, multimodal curricula over specific animation characteristics. CONCLUSION: SCS and DCTs both led to learning within a multimodal curriculum, but SCS significantly enhanced learner experience. Animation techniques exemplified by both SCS and DCTs have roles in the medical educator toolkit. Selection between them should incorporate context, learner factors, and production resources.


Assuntos
Tratamento Farmacológico da COVID-19 , Diabetes Mellitus , Internato e Residência , Carbonato de Cálcio , Currículo , Educação de Pós-Graduação em Medicina , Humanos , Pandemias
7.
Artif Organs ; 46(4): 688-696, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34694655

RESUMO

BACKGROUND: Veno-venous extracorporeal membrane oxygenation (V-V ECMO) support is increasingly used in the management of COVID-19-related acute respiratory distress syndrome (ARDS). However, the clinical decision-making to initiate V-V ECMO for severe COVID-19 still remains unclear. In order to determine the optimal timing and patient selection, we investigated the outcomes of both COVID-19 and non-COVID-19 patients undergoing V-V ECMO support. METHODS: Overall, 138 patients were included in this study. Patients were stratified into two cohorts: those with COVID-19 and non-COVID-19 ARDS. RESULTS: The survival in patients with COVID-19 was statistically similar to non-COVID-19 patients (p = .16). However, the COVID-19 group demonstrated higher rates of bleeding (p = .03) and thrombotic complications (p < .001). The duration of V-V ECMO support was longer in COVID-19 patients compared to non-COVID-19 patients (29.0 ± 27.5 vs 15.9 ± 19.6 days, p < .01). Most notably, in contrast to the non-COVID-19 group, we found that COVID-19 patients who had been on a ventilator for longer than 7 days prior to ECMO had 100% mortality without a lung transplant. CONCLUSIONS: These findings suggest that COVID-19-associated ARDS was not associated with a higher post-ECMO mortality than non-COVID-19-associated ARDS patients, despite longer duration of extracorporeal support. Early initiation of V-V ECMO is important for improved ECMO outcomes in COVID-19 ARDS patients. Since late initiation of ECMO was associated with extremely high mortality related to lack of pulmonary recovery, it should be used judiciously or as a bridge to lung transplantation.


Assuntos
COVID-19 , Oxigenação por Membrana Extracorpórea , Síndrome do Desconforto Respiratório , COVID-19/complicações , COVID-19/terapia , Oxigenação por Membrana Extracorpórea/efeitos adversos , Hemorragia/etiologia , Humanos , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/terapia , Estudos Retrospectivos , Fatores de Tempo
8.
Am J Respir Crit Care Med ; 204(8): 921-932, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34409924

RESUMO

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.

9.
Pain Pract ; 21(1): 75-82, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32654360

RESUMO

OBJECTIVES: Spinal cord stimulation (SCS) therapies are used in the management of patients with complex regional pain syndrome I (CRPS I) and failed back surgery syndrome (FBSS). The purpose of this study was to investigate the racial and health insurance inequalities with SCS therapy in patients with chronic pain who had CRPS I and FBSS. METHODS: Patients with chronic pain who had a discharge diagnosis of FBSS and CRPS I were identified using the National Inpatient Sample database. Our primary outcome was defined as the history of SCS utilization by race/ethnicity, income quartile, and insurance status. Multivariable logistic regression was used to determine the variables associated with utilization of SCS therapy. RESULTS: Between 2011 and 2015, 40,858 patients who were hospitalized with a primary diagnosis of FBSS and/or CRPS I were identified. Of these patients, 1,082 (2.7%) had a history of SCS therapy. Multivariable regression analysis revealed that compared to White patients, Black and Hispanic patients had higher odds of having SCS therapy (Black patients: odds ratio [OR] = 1.41; 95% confidence interval [CI], 1.12 to 1.77; P = 0.003; Hispanic patients: OR = 1.41; 95% CI, 1.10 to 1.81; P = 0.007). Patients with private insurance had significantly higher odds of having SCS therapy compared with those with Medicare (OR = 1.24; 95% CI, 1.08 to 1.43; P = 0.003). Compared to patients with Medicare, Medicaid patients had lower odds of having SCS therapy (OR = 0.50; 95% CI, 0.36 to 0.70; P < 0.001). CONCLUSIONS: Our study suggests that socioeconomic disparities may exist in the utilization of SCS among hospitalized patients with CRPS I and FBSS the United States. However, confirming these data from other administrative databases, in the outpatient setting, may shed more insight.


Assuntos
Dor Crônica/terapia , Disparidades em Assistência à Saúde/etnologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Manejo da Dor/estatística & dados numéricos , Fatores Socioeconômicos , Estimulação da Medula Espinal/estatística & dados numéricos , Adulto , Idoso , Dor Crônica/etiologia , Síndrome Pós-Laminectomia/complicações , Síndrome Pós-Laminectomia/terapia , Feminino , Disparidades em Assistência à Saúde/economia , Humanos , Masculino , Medicaid , Medicare , Pessoa de Meia-Idade , Manejo da Dor/economia , Distrofia Simpática Reflexa/complicações , Distrofia Simpática Reflexa/terapia , Estados Unidos
10.
Semin Respir Crit Care Med ; 40(5): 629-637, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31826263

RESUMO

Circadian rhythms are an integral part of life on earth. Circadian rhythms play a fundamental role in homeostasis as they ensure coordination between the environment and an organism's behavior and physiology. This coordination is called entrainment. Entrainment depends on environmental cues known as zeitgebers. Human zeitgebers include light (primary zeitgeber), sleep, eating, exercise, and activity. Circadian rhythms are disrupted in critically-ill patients due to both critical illness and current intensive care unit (ICU) practices. Disruptions in circadian rhythms are tightly linked with ICU sleep disruption. Together these entities potentiate numerous adverse outcomes including delirium, metabolic derangements, cardiovascular instability, and immune compromise. Herein, we will highlight potential areas for care improvement via chronobundles. We suggest bright light during the day, maintaining darkness, and protecting sleep at night, intermittent rather than continuous feeds, and activity via mobilization during the day. Optimizing circadian rhythms is a low-risk intervention that is underutilized in current ICU practice. This optimization could be a powerful tool in helping to improve outcomes in the critically-ill patient.


Assuntos
Ritmo Circadiano/fisiologia , Estado Terminal , Unidades de Terapia Intensiva , Animais , Cuidados Críticos/métodos , Humanos , Sono/fisiologia , Transtornos do Sono-Vigília/fisiopatologia , Transtornos do Sono-Vigília/prevenção & controle
11.
Teach Learn Med ; 30(3): 266-273, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29377731

RESUMO

Phenomenon: Although most premedical students shadow physicians prior to starting medical school, there is no set of guidelines or expectations to facilitate effective experiences for students and physicians, nor is there data on the value of shadowing medical trainees as a way to learn about the training environment. We sought to understand premedical student perspectives on an intensive resident shadowing experience. APPROACH: This was a qualitative study using anonymous data from focus groups conducted with premedical student participants in a month-long time motion analysis of internal medicine interns at two large academic medical centers. The authors convened, professionally transcribed verbatim, and analyzed data using step-by-step thematic analysis from 3 focus groups in 2012. Focus group questions included goals of participants, shadowing experiences, patient safety experiences, and thoughts on physician training. FINDINGS: Twenty of the 22 students who were involved in the time motion study participated in the focus groups (91%). Three major themes were generated from the transcripts: qualities of a good physician, the inefficiencies of the healthcare system and the hospital, and the realities of graduate medical education. Insights: The intensive shadowing experience exposed premedical students to the hospital environment and many of the challenges they will face as future residents. Observing patient care firsthand, students considered the qualities of good intern physicians and appreciated the teamwork and collaboration essential to patient care in an academic medical center. Students witnessed some of the fundamental challenges of graduate medical training, including time pressures, documentation requirements, and the medical hierarchy. They also observed the difficulties of providing quality care in the current healthcare system, including hospital inefficiencies, interprofessional tensions, and financial barriers to care. Intensive shadowing of residents can begin the process of socialization to the culture of medicine by giving premedical students a realistic perspective of both positive and negative aspects of medical training and inpatient care.


Assuntos
Medicina Interna/educação , Papel do Médico , Competência Clínica , Competência Cultural , Atenção à Saúde , Eficiência Organizacional , Feminino , Grupos Focais , Humanos , Relações Interprofissionais , Masculino , Assistência Centrada no Paciente , Pesquisa Qualitativa , Estudantes de Medicina
14.
PLoS Pathog ; 9(8): e1003579, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24009507

RESUMO

In Drosophila, post-transcriptional gene silencing occurs when exogenous or endogenous double stranded RNA (dsRNA) is processed into small interfering RNAs (siRNAs) by Dicer-2 (Dcr-2) in association with a dsRNA-binding protein (dsRBP) cofactor called Loquacious (Loqs-PD). siRNAs are then loaded onto Argonaute-2 (Ago2) by the action of Dcr-2 with another dsRBP cofactor called R2D2. Loaded Ago2 executes the destruction of target RNAs that have sequence complementarity to siRNAs. Although Dcr-2, R2D2, and Ago2 are essential for innate antiviral defense, the mechanism of virus-derived siRNA (vsiRNA) biogenesis and viral target inhibition remains unclear. Here, we characterize the response mechanism mediated by siRNAs against two different RNA viruses that infect Drosophila. In both cases, we show that vsiRNAs are generated by Dcr-2 processing of dsRNA formed during viral genome replication and, to a lesser extent, viral transcription. These vsiRNAs seem to preferentially target viral polyadenylated RNA to inhibit viral replication. Loqs-PD is completely dispensable for silencing of the viruses, in contrast to its role in silencing endogenous targets. Biogenesis of vsiRNAs is independent of both Loqs-PD and R2D2. R2D2, however, is required for sorting and loading of vsiRNAs onto Ago2 and inhibition of viral RNA expression. Direct injection of viral RNA into Drosophila results in replication that is also independent of Loqs-PD. This suggests that triggering of the antiviral pathway is not related to viral mode of entry but recognition of intrinsic features of virus RNA. Our results indicate the existence of a vsiRNA pathway that is separate from the endogenous siRNA pathway and is specifically triggered by virus RNA. We speculate that this unique framework might be necessary for a prompt and efficient antiviral response.


Assuntos
Interferência de RNA , Vírus de RNA/metabolismo , RNA Interferente Pequeno/metabolismo , RNA Viral/biossíntese , Viroses/metabolismo , Animais , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , RNA Helicases/genética , RNA Helicases/metabolismo , Vírus de RNA/genética , RNA Interferente Pequeno/genética , RNA Viral/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Ribonuclease III/genética , Ribonuclease III/metabolismo , Viroses/genética
15.
medRxiv ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38766045

RESUMO

Background: Pneumonia is the leading cause of infectious deaths and the most common infection identified in ICU patients. 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, but unclear operating characteristics in patients with immunocompromise and neutropenia remain unknown. Methods: We analyzed a large cohort of BALF specimens obtained for routine care for suspected pneumonia in mechanically ventilated patients and enrolled in the single-center Successful Clinical Response In Pneumonia Therapy (SCRIPT) study. BALF neutrophils were reported as a percentage of leukocytes by the clinical laboratory. The etiology of each episode of suspected pneumonia was adjudicated by a committee of critical care physicians using a predefined protocol. Immunocompromise was defined using predetermined criteria by the study research team. Neutropenia was defined here as a peripheral ANC <1500 cells/µl. Data are expressed as median [Quartile (Q) 1, Q3] and compared using the Mann-Whitney U test. Results: 688 mechanically ventilated patients with suspected pneumonia were included. 409 (59.4%) were male; median age was 62 [51,71]. 461 patients (67.0%) were immunocompetent, 149 (21.7%) were immunocompromised without neutropenia and 78 (11.3%) were neutropenic at some point during their admission. A total of 1746 BALs were performed. Fifty-seven BALs were obtained on a day where the patient's ANC<1500. Amongst pneumonia episodes classified as bacterial, no difference was found amongst BALF percent neutrophils taken patients who were immunocompetent and those who were immunocompromised but not neutropenic on day of sampling: 84.0% [69.0, 93.0] vs 87.0% [68.3, 93.0], p = 0.878 (Figure 1B). However, BALF percent neutrophils were significantly lower in patients neutropenic on day of sampling, with median BALF percent neutrophils of only 65.0% [22.3, 70.5] (p=0.016 compared with immunocompromised group, p=0.0096 compared with immunocompetent group). Conclusion: Among patients with bacterial pneumonia, BALF neutrophil percentage was not significantly decreased by a spectrum of immunocompromise. However, the subset of patients who were acutely neutropenic at the time of BAL sampling had significantly lower BALF % neutrophils. A traditional approach using BALF<50% to suggest against bacterial pneumonia may be inaccurate in this particular population.

16.
medRxiv ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38370841

RESUMO

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. We aimed to evaluate the BAL fluid GM and fungal culture results, demographics, and outcomes among a large cohort of mechanically ventilated patients with suspected pneumonia. Methods: A single-center cohort study of patients enrolled in the Successful Clinical Response in Pneumonia Therapy (SCRIPT) study from June 2018 to March 2023. Demographics, BAL results, and outcomes data were extracted from the electronic health record and compared between groups of patients who grew Aspergillus on a BAL fluid culture, those who had elevated BAL fluid GM levels (defined as >0.5 or >0.8) but did not grow Aspergillus on BAL fluid culture, and those with neither. Results: Of over 1700 BAL samples from 688 patients, only 18 BAL samples grew Aspergillus. Patients who had a BAL sample grow Aspergillus (n=15) were older (median 71 vs 62 years, p=0.023), had more days intubated (29 vs 11, p=0.002), and more ICU days (34 vs 15, p=0.002) than patients whose BAL fluid culture was negative for Aspergillus (n=672). The BAL fluid galactomannan level was higher from samples that grew Aspergillus on culture than those that did not (median ODI 7.08 vs 0.11, p<0.001), though the elevation of BAL fluid GM varied across BAL samples for patients who had serial sampling. Patients who grew Aspergillus had a similar proportion of underlying immunocompromise compared with the patients who did not, and while no statistically significant difference in overall unfavorable outcome, had longer duration of ventilation and longer ICU stays. Conclusions: In this large cohort of critically ill patients with a high number of BAL samples with GM levels, we found a relatively low rate of Aspergillus growth. Patients who eventually grew Aspergillus had inconsistently elevated BAL fluid GM, and many patients with elevated BAL fluid GM did not grow Aspergillus. These data suggest that the pre-test probability of invasive pulmonary aspergillosis should be considered low in a general ICU population undergoing BAL evaluation to define the etiology of pneumonia. Improved scoring systems are needed to enhance pre-test probability for diagnostic test stewardship purposes.

17.
J Bronchology Interv Pulmonol ; 30(1): 60-65, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35696591

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause severe respiratory failure leading to prolonged mechanical ventilation. Data are just emerging about the practice and outcomes of tracheostomy in these patients. We reviewed our experience with tracheostomies for SARS-CoV-2. METHODS: We retrospectively reviewed the demographics, comorbidities, timing of mechanical ventilation, tracheostomy, and intensive care unit and hospital lengths of stay in SARS-CoV-2 patients who received tracheostomies performed by the interventional pulmonary team. A tertiary care, teaching hospital in Chicago, Illinois. From March 2020 to April 2021, our center had 473 patients intubated for SARS-CoV-2, and 72 (15%) had percutaneous bedside tracheostomy performed by the interventional pulmonary team. RESULTS: Median time from intubation to tracheostomy was 20 (interquartile range: 16 to 25) days. Demographics and comorbidities were similar between early and late tracheostomy, but early tracheostomy was associated with shorter intensive care unit lengths of stay and a shorter total duration of ventilation. To date, 39 (54%) patients have been decannulated, 17 (24%) before hospital discharge; median time to decannulation was 22 (IQR: 18 to 36) days. Patients that were decannulated were younger (56 vs. 69 y). The rate of decannulation for survivors was 82%. No providers developed symptoms or tested positive for SARS-CoV-2. CONCLUSION: Tracheostomy enhances care for patients with prolonged respiratory failure from SARS-CoV-2 since early tracheostomy is associated with shorter duration of critical care, and decannulation rates are high for survivors. It furthermore appears safe for both patients and operators.


Assuntos
COVID-19 , Insuficiência Respiratória , Humanos , SARS-CoV-2 , Traqueostomia/efeitos adversos , Estudos Retrospectivos , Respiração Artificial , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Unidades de Terapia Intensiva
18.
medRxiv ; 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37066228

RESUMO

Objective ChatGPT is the first large language model (LLM) to reach a large, mainstream audience. Its rapid adoption and exploration by the population at large has sparked a wide range of discussions regarding its acceptable and optimal integration in different areas. In a hybrid (virtual and in-person) panel discussion event, we examined various perspectives regarding the use of ChatGPT in education, research, and healthcare. Materials and Methods We surveyed in-person and online attendees using an audience interaction platform (Slido). We quantitatively analyzed received responses on questions about the use of ChatGPT in various contexts. We compared pairwise categorical groups with Fisher's Exact. Furthermore, we used qualitative methods to analyze and code discussions. Results We received 420 responses from an estimated 844 participants (response rate 49.7%). Only 40% of the audience had tried ChatGPT. More trainees had tried ChatGPT compared with faculty. Those who had used ChatGPT were more interested in using it in a wider range of contexts going forwards. Of the three discussed contexts, the greatest uncertainty was shown about using ChatGPT in education. Pros and cons were raised during discussion for the use of this technology in education, research, and healthcare. Discussion There was a range of perspectives around the uses of ChatGPT in education, research, and healthcare, with still much uncertainty around its acceptability and optimal uses. There were different perspectives from respondents of different roles (trainee vs faculty vs staff). More discussion is needed to explore perceptions around the use of LLMs such as ChatGPT in vital sectors such as education, healthcare and research. Given involved risks and unforeseen challenges, taking a thoughtful and measured approach in adoption would reduce the likelihood of harm.

19.
PLoS One ; 18(10): e0292216, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37796786

RESUMO

OBJECTIVE: ChatGPT is the first large language model (LLM) to reach a large, mainstream audience. Its rapid adoption and exploration by the population at large has sparked a wide range of discussions regarding its acceptable and optimal integration in different areas. In a hybrid (virtual and in-person) panel discussion event, we examined various perspectives regarding the use of ChatGPT in education, research, and healthcare. MATERIALS AND METHODS: We surveyed in-person and online attendees using an audience interaction platform (Slido). We quantitatively analyzed received responses on questions about the use of ChatGPT in various contexts. We compared pairwise categorical groups with a Fisher's Exact. Furthermore, we used qualitative methods to analyze and code discussions. RESULTS: We received 420 responses from an estimated 844 participants (response rate 49.7%). Only 40% of the audience had tried ChatGPT. More trainees had tried ChatGPT compared with faculty. Those who had used ChatGPT were more interested in using it in a wider range of contexts going forwards. Of the three discussed contexts, the greatest uncertainty was shown about using ChatGPT in education. Pros and cons were raised during discussion for the use of this technology in education, research, and healthcare. DISCUSSION: There was a range of perspectives around the uses of ChatGPT in education, research, and healthcare, with still much uncertainty around its acceptability and optimal uses. There were different perspectives from respondents of different roles (trainee vs faculty vs staff). More discussion is needed to explore perceptions around the use of LLMs such as ChatGPT in vital sectors such as education, healthcare and research. Given involved risks and unforeseen challenges, taking a thoughtful and measured approach in adoption would reduce the likelihood of harm.


Assuntos
Docentes , Inclusão Escolar , Humanos , Escolaridade , Instalações de Saúde , Probabilidade
20.
NPJ Digit Med ; 6(1): 75, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37100871

RESUMO

Large language models such as ChatGPT can produce increasingly realistic text, with unknown information on the accuracy and integrity of using these models in scientific writing. We gathered fifth research abstracts from five high-impact factor medical journals and asked ChatGPT to generate research abstracts based on their titles and journals. Most generated abstracts were detected using an AI output detector, 'GPT-2 Output Detector', with % 'fake' scores (higher meaning more likely to be generated) of median [interquartile range] of 99.98% 'fake' [12.73%, 99.98%] compared with median 0.02% [IQR 0.02%, 0.09%] for the original abstracts. The AUROC of the AI output detector was 0.94. Generated abstracts scored lower than original abstracts when run through a plagiarism detector website and iThenticate (higher scores meaning more matching text found). When given a mixture of original and general abstracts, blinded human reviewers correctly identified 68% of generated abstracts as being generated by ChatGPT, but incorrectly identified 14% of original abstracts as being generated. Reviewers indicated that it was surprisingly difficult to differentiate between the two, though abstracts they suspected were generated were vaguer and more formulaic. ChatGPT writes believable scientific abstracts, though with completely generated data. Depending on publisher-specific guidelines, AI output detectors may serve as an editorial tool to help maintain scientific standards. The boundaries of ethical and acceptable use of large language models to help scientific writing are still being discussed, and different journals and conferences are adopting varying policies.

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