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OBJECTIVES: We aimed to report the emergence of azole-resistant invasive aspergillosis in hematologic patients admitted to a tertiary hospital in Spain during the last 4 months. METHODS: Prospective, descriptive study was performed to describe and follow all consecutive proven and probable invasive aspergillosis resistant to azoles from hematological cohort during the last 4 months. All patients had fungal cultures and antifungal susceptibility or real-time PCR detection for Aspergillus species and real-time PCR detection for azole-resistant mutation. RESULTS: Four cases of invasive aspergillosis were diagnosed in 4 months. Three of them had azole-resistant aspergillosis. Microbiological diagnosis was achieved in three cases by means of fungal culture isolation and subsequent antifungal susceptibility whereas one case was diagnosed by PCR-based aspergillus and azole resistance detection. All the azole-resistant aspergillosis presented TR34/L98H mutation. Patients with azole-resistant aspergillosis had different hematologic diseases: multiple myeloma, lymphoblastic acute leukemia, and angioimmunoblastic T lymphoma. Regarding risk factors, one had prolonged neutropenia, two had corticosteroids, and two had viral co-infection. Two of the patients developed aspergillosis under treatment with azoles. CONCLUSION: We have observed a heightened risk of azole-resistant aspergillosis caused by A. fumigatus harboring the TR34/L98H mutation in patients with hematologic malignancies. The emergence of azole-resistant aspergillosis raises concerns for the community, highlighting the urgent need for increased surveillance and the importance of susceptibility testing and new drugs development.
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BACKGROUND: Cytomegalovirus (CMV) infection in patients with cellular immune deficiencies is associated with significant morbidity and mortality. However, data on CMV end-organ disease (CMV-EOD) in critically ill, immunocompromised patients are scarce. Our objective here was to describe the clinical characteristics and outcomes of CMV-EOD in this population. METHODS: We conducted a multicenter, international, retrospective, observational study in adults who had CMV-EOD and were admitted to any of 18 intensive care units (ICUs) in France, Israel, and Spain in January 2010-December 2021. Patients with AIDS were excluded. We collected the clinical characteristics and outcomes of each patient. Survivors and non-survivors were compared, and multivariate analysis was performed to identify risk factors for hospital mortality. RESULTS: We studied 185 patients, including 80 (43.2%) with hematologic malignancies, 55 (29.7%) with solid organ transplantation, 31 (16.8%) on immunosuppressants, 16 (8.6%) with solid malignancies, and 3 (1.6%) with primary immunodeficiencies. The most common CMV-EOD was pneumonia (n = 115, [62.2%] including 55 [47.8%] with a respiratory co-pathogen), followed by CMV gastrointestinal disease (n = 64 [34.6%]). More than one organ was involved in 16 (8.8%) patients. Histopathological evidence was obtained for 10/115 (8.7%) patients with pneumonia and 43/64 (67.2%) with GI disease. Other opportunistic infections were diagnosed in 69 (37.3%) patients. Hospital mortality was 61.4% overall and was significantly higher in the group with hematologic malignancies (75% vs. 51%, P = 0.001). Factors independently associated with higher hospital mortality were hematologic malignancy with active graft-versus-host disease (OR 5.02; 95% CI 1.15-27.30), CMV pneumonia (OR 2.57; 95% CI 1.13-6.03), lymphocytes < 0.30 × 109/L at diagnosis of CMV-EOD (OR 2.40; 95% CI 1.05-5.69), worse SOFA score at ICU admission (OR 1.18; 95% CI 1.04-1.35), and older age (OR 1.04; 95% CI 1.01-1.07). CONCLUSIONS: Mortality was high in critically ill, immunocompromised patients with CMV-EOD and varied considerably with the cause of immunodeficiency and organ involved by CMV. Three of the four independent risk factors identified here are also known to be associated with higher mortality in the absence of CMV-EOD. CMV pneumonia was rarely proven by histopathology and was the most severe CMV-EOD.
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Estado Terminal , Infecções por Citomegalovirus , Hospedeiro Imunocomprometido , Humanos , Estudos Retrospectivos , Masculino , Feminino , Infecções por Citomegalovirus/imunologia , Pessoa de Meia-Idade , Idoso , Espanha/epidemiologia , Estudos de Coortes , Unidades de Terapia Intensiva/estatística & dados numéricos , Unidades de Terapia Intensiva/organização & administração , França/epidemiologia , Adulto , Israel/epidemiologia , Mortalidade Hospitalar , Citomegalovirus/imunologia , Citomegalovirus/patogenicidade , Fatores de RiscoRESUMO
BACKGROUND: Recently, validated clinical decision rules have been developed that avoid unnecessary use of computed tomographic pulmonary angiography (CTPA) in patients with suspected pulmonary embolism (PE) in the emergency department (ED). OBJECTIVE: To measure any resulting change in CTPA use for suspected PE. DESIGN: Retrospective analysis. SETTING: 26 European EDs in 6 countries. PATIENTS: Patients with CTPA performed for suspected PE in the ED during the first 7 days of each odd month between January 2015 and December 2019. MEASUREMENTS: The primary end points were the CTPAs done for suspected PE in the ED and the number of PEs diagnosed in the ED each year adjusted to an annual census of 100 000 ED visits. Temporal trends were estimated using generalized linear mixed regression models. RESULTS: 8970 CTPAs were included (median age, 63 years; 56% female). Statistically significant temporal trends for more frequent use of CTPA (836 per 100 000 ED visits in 2015 vs. 1112 in 2019; P < 0.001), more diagnosed PEs (138 per 100 000 in 2015 vs. 164 in 2019; P = 0.028), a higher proportion of low-risk PEs (annual percent change [APC], 13.8% [95% CI, 2.6% to 30.1%]) with more ambulatory management (APC, 19.3% [CI, 4.1% to 45.1%]), and a lower proportion of intensive care unit admissions (APC, -8.9% [CI, -17.1% to -0.3%]) were observed. LIMITATION: Data were limited to 7 days every 2 months. CONCLUSION: Despite the recent validation of clinical decision rules to limit the use of CTPA, an increase in the CTPA rate along with more diagnosed PEs and especially low-risk PEs were instead observed. PRIMARY FUNDING SOURCE: None specific for this study.
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Embolia Pulmonar , Tomografia Computadorizada por Raios X , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Embolia Pulmonar/diagnóstico por imagem , Serviço Hospitalar de Emergência , AngiografiaRESUMO
Accurate prediction of COVID-19 severity remains a challenge. Torque teno virus (TTV), recognized as a surrogate marker of functional immunity in solid organ transplant recipients, holds the potential for assessing infection outcomes. We investigated whether quantifying TTV in nasopharyngeal samples upon emergency department (ED) admission could serve as an early predictor of COVID-19 severity. Retrospective single-center study in the ED of Saint-Louis Hospital in Paris, France. TTV DNA was quantified in nasopharyngeal swab samples collected for SARS-CoV-2 testing. Among 295 SARS-CoV-2 infected patients, 92 returned home, 160 were admitted to medical wards, and 43 to the intensive care unit (ICU). Elevated TTV loads were observed in ICU patients (median: 3.02 log copies/mL, interquartile range [IQR]: 2.215-3.825), exceeding those in discharged (2.215, [0; 2.962]) or hospitalized patients (2.24, [0; 3.29]) (p = 0.006). Multivariate analysis identified diabetes, obesity, hepatitis, fever, dyspnea, oxygen requirement, and TTV load as predictors of ICU admission. A 2.91 log10 copies/mL TTV threshold independently predicted ICU admission. Nasopharyngeal TTV quantification in SARS-CoV-2 infected patients is linked to the likelihood of ICU admission and might reflect respiratory immunosuppression.
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COVID-19 , Infecções por Vírus de DNA , Torque teno virus , Humanos , Torque teno virus/genética , SARS-CoV-2/genética , Estudos Retrospectivos , Teste para COVID-19 , COVID-19/diagnóstico , DNA Viral , Unidades de Terapia Intensiva , Carga ViralRESUMO
BACKGROUND: At the end of 2021, the B.1.1.529 SARS-CoV-2 variant (Omicron) wave superseded the B.1.617.2 variant (Delta) wave. OBJECTIVE: To compare baseline characteristics and in-hospital outcomes of patients with SARS-CoV-2 infection with the Delta variant versus the Omicron variant in the emergency department (ED). DESIGN: Retrospective chart reviews. SETTING: 13 adult EDs in academic hospitals in the Paris area from 29 November 2021 to 10 January 2022. PATIENTS: Patients with a positive reverse transcriptase polymerase chain reaction (RT-PCR) test result for SARS-CoV-2 and variant identification. MEASUREMENTS: Main outcome measures were baseline clinical and biological characteristics at ED presentation, intensive care unit (ICU) admission, mechanical ventilation, and in-hospital mortality. RESULTS: A total of 3728 patients had a positive RT-PCR test result for SARS-CoV-2 during the study period; 1716 patients who had a variant determination (818 Delta and 898 Omicron) were included. Median age was 58 years, and 49% were women. Patients infected with the Omicron variant were younger (54 vs. 62 years; difference, 8.0 years [95% CI, 4.6 to 11.4 years]), had a lower rate of obesity (8.0% vs. 12.5%; difference, 4.5 percentage points [CI, 1.5 to 7.5 percentage points]), were more vaccinated (65% vs. 39% for 1 dose and 22% vs. 11% for 3 doses), had a lower rate of dyspnea (26% vs. 50%; difference, 23.6 percentage points [CI, 19.0 to 28.2 percentage points]), and had a higher rate of discharge home from the ED (59% vs. 37%; difference, 21.9 percentage points [-26.5 to -17.1 percentage points]). Compared with Delta, Omicron infection was independently associated with a lower risk for ICU admission (adjusted difference, 11.4 percentage points [CI, 8.4 to 14.4 percentage points]), mechanical ventilation (adjusted difference, 3.6 percentage points [CI, 1.7 to 5.6 percentage points]), and in-hospital mortality (adjusted difference, 4.2 percentage points [CI, 2.0 to 6.5 percentage points]). LIMITATION: Patients with COVID-19 illness and no SARS-CoV-2 variant determination in the ED were excluded. CONCLUSION: Compared with the Delta variant, infection with the Omicron variant in patients in the ED had different clinical and biological patterns and was associated with better in-hospital outcomes, including higher survival. PRIMARY FUNDING SOURCE: None.
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COVID-19 , SARS-CoV-2 , Adulto , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paris/epidemiologia , Estudos Retrospectivos , SARS-CoV-2/genéticaRESUMO
STUDY OBJECTIVE: We seek to describe the medical history and clinical findings of patients attending the emergency department (ED) with suspected coronavirus disease 2019 (COVID-19) and estimate the diagnostic accuracy of patients' characteristics for predicting COVID-19. METHODS: We prospectively enrolled all patients tested for severe acute respiratory syndrome coronavirus 2 by reverse-transcriptase polymerase chain reaction in our ED from March 9, 2020, to April 4, 2020. We abstracted medical history, physical examination findings, and the clinical probability of COVID-19 (low, moderate, and high) rated by emergency physicians, depending on their clinical judgment. We assessed diagnostic accuracy of these characteristics for COVID-19 by calculating positive and negative likelihood ratios. RESULTS: We included 391 patients, of whom 225 had positive test results for severe acute respiratory syndrome coronavirus 2. Reverse-transcriptase polymerase chain reaction result was more likely to be negative when the emergency physician thought that clinical probability was low, and more likely to be positive when he or she thought that it was high. Patient-reported anosmia and the presence of bilateral B lines on lung ultrasonography had the highest positive likelihood ratio for the diagnosis of COVID-19 (7.58, 95% confidence interval [CI] 2.36 to 24.36; and 7.09, 95% CI 2.77 to 18.12, respectively). The absence of a high clinical probability determined by the emergency physician and the absence of bilateral B lines on lung ultrasonography had the lowest negative likelihood ratio for the diagnosis of COVID-19 (0.33, 95% CI 0.25 to 0.43; and 0.26, 95% CI 0.15 to 0.45, respectively). CONCLUSION: Anosmia, emergency physician estimate of high clinical probability, and bilateral B lines on lung ultrasonography increased the likelihood of identifying COVID-19 in patients presenting to the ED.
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Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Serviço Hospitalar de Emergência/normas , Pneumonia Viral/diagnóstico , Adulto , Idoso , Betacoronavirus , COVID-19 , Teste para COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Feminino , França , Humanos , Pulmão/diagnóstico por imagem , Masculino , Anamnese , Pessoa de Meia-Idade , Transtornos do Olfato/virologia , Pandemias , Exame Físico , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Probabilidade , Estudos Prospectivos , Radiografia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2 , UltrassonografiaRESUMO
Immune checkpoint inhibitors (ICIs) are of growing importance in new cancer therapies, exposing patients to various and potentially severe immune-related adverse events and placing emergency physicians on the front line when they occur. If endocrine toxicity is a well-known complication of ICIs, fulminant diabetes with diabetic ketoacidosis is exceptional. We present a case of fulminant diabetes after only two cycles of pembrolizumab in a 53-year-old man with a history of metastatic lung cancer who presented to our emergency department with coma and acidosis revealing diabetic ketoacidosis. The patient was rehydrated and treated with insulin and recovered quickly. Lung toxicity was also suspected on CT-scan findings. This rare and life-threatening complication that developed unusually early during the treatment course may be challenging in a cancer patient. Therefore, emergency physicians should investigate symptoms in patients treated with checkpoint inhibitors and consider toxicity when they present to the ED with complaints compatible with an immune-related adverse event.
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Antineoplásicos Imunológicos/efeitos adversos , Cetoacidose Diabética/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Anticorpos Monoclonais Humanizados , Cetoacidose Diabética/tratamento farmacológico , Serviço Hospitalar de Emergência , Humanos , Insulina/uso terapêutico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The evaluation process of French medical students will evolve in the next few years in order to improve assessment validity. Script concordance testing (SCT) offers the possibility to assess medical knowledge alongside clinical reasoning under conditions of uncertainty. In this study, we aimed at comparing the SCT scores of a large cohort of undergraduate medical students, according to the experience level of the reference panel. METHODS: In 2019, the authors developed a 30-item SCT and sent it to experts with varying levels of experience. Data analysis included score comparisons with paired Wilcoxon rank sum tests and concordance analysis with Bland & Altman plots. RESULTS: A panel of 75 experts was divided into three groups: 31 residents, 21 non-experienced physicians (NEP) and 23 experienced physicians (EP). Among each group, random samples of N = 20, 15 and 10 were selected. A total of 985 students from nine different medical schools participated in the SCT examination. No matter the size of the panel (N = 20, 15 or 10), students' SCT scores were lower with the NEP group when compared to the resident panel (median score 67.1 vs 69.1, p < 0.0001 if N = 20; 67.2 vs 70.1, p < 0.0001 if N = 15 and 67.7 vs 68.4, p < 0.0001 if N = 10) and with EP compared to NEP (65.4 vs 67.1, p < 0.0001 if N = 20; 66.0 vs 67.2, p < 0.0001 if N = 15 and 62.5 vs 67.7, p < 0.0001 if N = 10). Bland & Altman plots showed good concordances between students' SCT scores, whatever the experience level of the expert panel. CONCLUSIONS: Even though student SCT scores differed statistically according to the expert panels, these differences were rather weak. These results open the possibility of including less-experienced experts in panels for the evaluation of medical students.
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Estudantes de Medicina , Competência Clínica , Avaliação Educacional , Humanos , Estatísticas não Paramétricas , IncertezaRESUMO
Invasive pulmonary aspergillosis (IPA) is a fungal infection that is the hallmark of severe cellular or complex immune alterations. Evidence that IPA can occur in nonimmunocompromised hosts is increasing. Actually, up to 1% of general intensive care unit (ICU) patients present positive samples with Aspergillus spp. Both colonization and invasive disease are associated with poor outcome. Unexpected IPA has also been reported in approximately 1% of critically ill patients who underwent postmortem biopsies. In nonimmunocompromised patients with acute respiratory distress syndrome (ARDS), IPA prevalence can reach up to 15% of patients in both clinical and autopsy studies. Factors associated with IPA in nonimmunocompromised critically ill hosts include short and long courses of steroids, broad antibiotic therapy, chronic obstructive pulmonary disease, ARDS, liver failure, and the severity of organ dysfunctions.This review aims to appraise the prevalence of IPA in nonimmunocompromised hosts, address diagnostic challenges, and outcomes.
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Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Antifúngicos/uso terapêutico , Estado Terminal/terapia , Humanos , Tolerância Imunológica , Hospedeiro Imunocomprometido , Aspergilose Pulmonar Invasiva/mortalidade , Prevalência , Doença Pulmonar Obstrutiva Crônica/complicações , Síndrome do Desconforto Respiratório/complicações , Fatores de Risco , Sepse/complicaçõesRESUMO
With the overall improvement in survival of cancer patients and the widespread use of novel immunotherapy drugs for malignant as well as nonmalignant diseases, the prevalence of immunosuppression is rising in the population. Immunocompromised patients are particularly exposed to pulmonary infections which remain a leading cause for acute hypoxic respiratory failure and intensive care unit admission. Although fungal or opportunistic infections are always a concern, bacterial pneumonia remains the most common cause of pulmonary infection, is associated with a significant mortality, and has some specificity in this population. Adequate and timely prevention, diagnosis, and management of bacterial pneumonias require knowledge about the complex interplay between host factors (type and severity of immunosuppression) and bacterial pathogenesis, to improve the outcome. We provide an overview of bacterial pneumonias in immunocompromised patients including their epidemiology, risk factors with respect to the pattern of immunosuppression, microbiological characteristics, diagnostic approach, management, and prevention.
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Antibacterianos/uso terapêutico , Infecção Hospitalar/imunologia , Hospedeiro Imunocomprometido , Pneumonia Bacteriana/imunologia , Antibacterianos/farmacologia , Sobreviventes de Câncer , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Humanos , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/epidemiologia , Fatores de RiscoRESUMO
OBJECTIVES: We sought to estimate the prevalence of patients with cancer presenting to the emergency department (ED) who are undergoing treatment with immune checkpoint blockade (ICB) therapy; report their chief complaints; describe and estimate the prevalence of immune-related adverse events (IRAEs). METHODS: Four abstractors reviewed the medical records of patients with cancer treated with ICB who presented to an ED in Paris, France between January 2012 and June 2017. Chief complaints, underlying malignancy and ICB characteristics, and the final diagnoses according to the emergency physician were recorded. Abstractors noted if an emergency physician identified that a patient was receiving an ICB and if the emergency physician considered the possibility of an IRAE. The gold standard as to whether an IRAE was the cause was the patients' referring oncologist's opinion that the ED symptoms were attributed to ICB and IRAE according to post-ED medical records. Descriptive statistics were reported. RESULTS: Among the 409 patients treated with ICB at our institution, 139 presented to the ED. Chief complaints were fatigue (25.2%), fever (23%), vomiting (13.7%), diarrhoea (13.7%), dyspnoea (12.2%), abdominal pain (11.5%), confusion (8.6%) and headache (7.9%). Symptoms were due to IRAEs in 20 (14.4%) cases. The most frequent IRAEs were colitis (40%), endocrine toxicity (30%), hepatitis (25%) and pulmonary toxicity (5%). Patients with IRAEs compared with those without them more frequently had melanoma; had received more distinct courses of ICB treatment, an increased number of ICB medications and ICB cycles; and had a shorter time course since the last infusion of ICB. Emergency physicians considered the possibility of an IRAE in 24 (17.3%) of cases and diagnosed IRAE in 10 (50%) of those with later confirmed IRAE. IRAE was more likely to be missed when the referring oncologist was not contacted or when the patient had respiratory symptoms, fatigue or fever. CONCLUSIONS: ICB exposes patients to potentially severe IRAEs. Emergency physicians must identify patients treated with ICB and consider their toxicity when patients present to the ED with symptoms compatible with IRAEs.
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Antineoplásicos Imunológicos/toxicidade , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Neoplasias/tratamento farmacológico , Idoso , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/toxicidade , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/toxicidade , Antineoplásicos Imunológicos/uso terapêutico , Serviço Hospitalar de Emergência/organização & administração , Serviço Hospitalar de Emergência/estatística & dados numéricos , Fadiga/etiologia , Feminino , Febre/etiologia , Humanos , Ipilimumab/uso terapêutico , Ipilimumab/toxicidade , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Nivolumabe/uso terapêutico , Nivolumabe/toxicidade , Paris/epidemiologia , Prevalência , Estudos Retrospectivos , Vômito/etiologiaRESUMO
Importance of bedside ultrasonography (BU) is growing in the emergency medicine. Many reasons support the use of the focused ultrasounds in the emergencies services such asâ : helping in diagnosis, improving invasive gestures and other treatments strategies. The implementation of a focused ultrasonography has a low financial impact but a high educational value. In despite of the existent education and training programs, the focused ultrasonography only has a low diffusion/practice in the emergency departments in Suisse romande. Here we describe the implementation on a focused ultrasonography program for our institution (HFRâ : Hôpital fribourgeois).
L'échographie ciblée est un outil essentiel dans la prise en charge des patients en médecine d'urgence. Utilisée comme complément de l'examen clinique elle constitue une aide au diagnostic, permet d'évaluer les traitements entrepris et de sécuriser les gestes invasifs. La mise en place d'un programme de formation à l'échographie ciblée a un faible impact financier mais une grande valeur éducative. En dépit de ses avantages et de l'existence de formations, on constate une faible diffusion de l'échographie ciblée dans les services d'urgences en Suisse romande. Nous écrivons ici le processus de mise en place d'un programme d'implémentation de l'échographie ciblée dans notre institution (HFRâ : Hôpital fribourgeois).
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Serviços Médicos de Emergência , Medicina de Emergência , Sistemas Automatizados de Assistência Junto ao Leito , Ultrassonografia , Serviço Hospitalar de Emergência , HumanosRESUMO
Detection of viral and bacterial DNA in nasopharyngeal aspirates (NPAs) is now a routine practice in emergency cases of febrile pneumonia. We investigated whether Pneumocystis jirovecii DNA could also be detected in these cases by conducting retrospective screening of 324 consecutive NPAs from 324 adult patients (198 or 61% were immunocompromised) admitted with suspected pulmonary infections during the 2012 influenza epidemic season, using a real-time quantitative polymerase chain reaction (PCR) assay (PjqPCR), which targets the P. jirovecii mitochondrial large subunit ribosomal RNA gene. These NPAs had already been tested for 22 respiratory pathogens (18 viruses and 4 bacteria), but we found that 16 NPAs (4.9%) were PjqPCR-positive, making P. jirovecii the fourth most prevalent of the 23 microorganisms in the screen. Eleven of the 16 PjqPCR-positive patients were immunocompromised, and five had underlying pulmonary conditions. Nine NPAs were also positive for another respiratory pathogen. Six had PjqPCR-positive induced sputa less than 3 days after the NPA procedure, and five were diagnosed with pneumocystis pneumonia (four with chronic lymphoproliferative disorders and one AIDS patient). In all six available pairs quantification of P. jirovecii DNA showed fewer copies in NPA than in induced sputum and three PjqPCR-negative NPAs corresponded to PjqPCR-positive bronchoalveolar lavage fluids, underscoring the fact that a negative PjqPCR screen does not exclude a diagnosis of pneumocystosis. Including P. jirovecii DNA detection to the panel of microorganisms included in screening tests used for febrile pneumonia may encourage additional investigations or support use of anti-pneumocystis pneumonia prophylaxis in immunocompromised patients.
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DNA Fúngico/isolamento & purificação , Febre de Causa Desconhecida/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Nasofaringe/microbiologia , Pneumocystis carinii/isolamento & purificação , Pneumonia/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , DNA Fúngico/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Feminino , Febre de Causa Desconhecida/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pneumocystis carinii/genética , Pneumonia/microbiologia , RNA Ribossômico/genética , Adulto JovemRESUMO
INTRODUCTION: Artificial intelligence (AI) and machine learning (ML) have the potential to revolutionize the management of febrile neutropenia (FN) and drive progress toward personalized medicine. AREAS COVERED: In this review, we detail how the collection of a large number of high-quality data can be used to conduct precise mathematical studies with ML and AI. We explain the foundations of these techniques, covering the fundamentals of supervised and unsupervised learning, as well as the most important challenges, e.g. data quality, 'black box' model interpretation and overfitting. To conclude, we provide detailed examples of how AI and ML have been used to enhance predictions of chemotherapy-induced FN, detection of bloodstream infections (BSIs) and multidrug-resistant (MDR) bacteria, and anticipation of severe complications and mortality. EXPERT OPINION: There is promising potential of implementing accurate AI and ML models whilst managing FN. However, their integration as viable clinical tools poses challenges, including technical and implementation barriers. Improving global accessibility, fostering interdisciplinary collaboration, and addressing ethical and security considerations are essential. By overcoming these challenges, we could transform personalized care for patients with FN.
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Neutropenia Febril Induzida por Quimioterapia , Neoplasias , Humanos , Inteligência Artificial , Aprendizado de Máquina , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Medicina de PrecisãoRESUMO
To estimate the rate of inappropriate diagnosis in patients who visited the ED with thrombotic microangiopathy (TMA) and to assess the factors and outcomes associated with emergency department (ED) misdiagnosis. Retrospective multicenter study of adult patients admitted to the intensive care unit (ICU) for TMA from 2012 to 2021 who had previously attended the ED for a reason related to TMA. Patient characteristics and outcomes were compared in a univariate analysis based on whether a TMA diagnosis was mentioned in the ED or not. Forty patients were included. The diagnosis of TMA was not mentioned in the ED in 16 patients (40%). Patients for whom the diagnosis was mentioned in the ED had more frequently a request for schistocytes research, and therefore had more often objectified schistocytes. They also had more frequently a troponin dosage in the ED (even if the difference was not significant), an ECG performed or interpreted, and were admitted more quickly in the ICU (0 [0-0] vs 2 [0-2] days; P = 0.002). Hemoglobin levels decreased significantly in both groups, and creatinine levels increased significantly in the misdiagnosis group between ED arrival and ICU admission. In patients with a final diagnosis of TTP, the time to platelets durable recovery was shorter for those in whom the diagnosis was mentioned in the ED without reaching statistical significance (7 [5-11] vs 14 [5-21] days; P = 0.3).
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Síndrome Hemolítico-Urêmica , Púrpura Trombocitopênica Trombótica , Microangiopatias Trombóticas , Adulto , Humanos , Púrpura Trombocitopênica Trombótica/diagnóstico , Síndrome Hemolítico-Urêmica/diagnóstico , Estudos Retrospectivos , Microangiopatias Trombóticas/diagnóstico , Serviço Hospitalar de Emergência , Erros de DiagnósticoRESUMO
BACKGROUND: We aimed to describe a cohort of hematologic patients with COVID-19 treated with antivirals early. METHODS: Non-interventional chart review study. Comparison of baseline characteristics and outcomes in high-risk hematologic patients treated with remdesivir between December 2021 and April 2022 versus those treated with nirmatrelvir/ritonavir between May and August 2022. RESULTS: Eighty-three patients were analyzed. Forty-two received remdesivir, and 41 nirmatrelvir/ritonavir. Patients with remdesivir were younger, vaccinated with lower number of doses, and received prior corticosteroids less frequently and sotrovimab, hyperimmune plasma and corticosteroids more often. Viral shedding median (IQR) duration was 18 (13-23) and 11 (8-21) days in the remdesivir and nirmatrelvir/ritonavir groups, respectively (p = 0.004). Median (IQR) Ct values before treatment were similar in both groups. Within 5 days of treatment, median (IQR) Ct values were 26 (23-29) and 33 (30-37) in the remdesivir and nirmatrelvir/ritonavir groups, respectively (p < 0.0001). All patients were hospitalized for remdesivir administration and only four (9.8%) in the nirmatrelvir/ritonavir group. The overall outcomes in this cohort of COVID-19 patients with Omicron variant was good, as no patient needed oxygen or ICU admission. One patient in remdesivir group died from septic shock. No severe adverse event was recorded in both treatment groups. CONCLUSIONS: Patients with hematologic malignancies and non-severe COVID-19 who received nirmatrelvir/ritonavir experienced faster decrease in viral load and shorter viral shedding. Furthermore, besides the advantage of oral administration, nirmatrelvir/ritonavir administration reduced the need of hospital admission.
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COVID-19 , Neoplasias Hematológicas , Lactamas , Leucina , Nitrilas , Prolina , Humanos , Ritonavir/uso terapêutico , SARS-CoV-2 , Corticosteroides , Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19RESUMO
INTRODUCTION: Identifying infection etiology in febrile neutropenia (FN) is vital. This study explores different microbiological approaches and their impact on diagnosing infections in patients with hematologic malignancies and FN. METHODS: Retrospective analysis conducted at Hospital Clinic of Barcelona details microbiological testing strategies used to diagnose infections at FN onset between January 2020 and July 2022. RESULTS: 4520 microbiological tests were ordered in 462 FN episodes, achieving a 10% test positivity rate with 200 (43.3%) episodes showing microbiological documentation of infection. Blood cultures (40.4%), non-culture blood tests (21.2%), respiratory tract samples (16.2%), were the most requested. Blood cultures exhibited the highest (16.9%) test positivity rates while non-culture blood tests showed the lowest (3.3%). Bacterial infections were present in 149/462 (32.3%) FN episodes. Viral infections (66/462, 14.3%)-notably respiratory viruses-were also frequent. Mortality rate at 60 days was 9.1%; documented infections were associated with a higher risk (15%). CONCLUSIONS: In the current landscape of antimicrobial diagnostics, our findings revealed the highest reported rate of microbiologically documented infections at FN onset. Bacterial infections are common; however, our data reiterates the significance of viral infections in causing fever. Optimizing FN management during respiratory viral infections remains a challenge for antimicrobial de-escalation. The low positivity rates observed in certain diagnostic tests emphasize the need for cost-effective diagnostic stewardship.
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INTRODUCTION: The impact of remdesivir on mortality in patients with COVID-19 is still controversial. We aimed to identify clinical phenotype clusters of COVID-19 hospitalized patients with highest benefit from remdesivir use and validate these findings in an external cohort. METHODS: We included consecutive patients hospitalized between February 2020 and February 2021 for COVID-19. The derivation cohort comprised subjects admitted to Hospital Clinic of Barcelona. The validation cohort included patients from Hospital Universitari Mutua de Terrassa (Terrassa) and Hospital Universitari La Fe (Valencia), all tertiary centers in Spain. We employed K-means clustering to group patients according to reverse transcription polymerase chain reaction (rRT-PCR) cycle threshold (Ct) values and lymphocyte counts at diagnosis, and pre-test symptom duration. The impact of remdesivir on 60-day mortality in each cluster was assessed. RESULTS: A total of 1160 patients (median age 66, interquartile range (IQR) 55-78) were included. We identified five clusters, with mortality rates ranging from 0 to 36.7%. Highest mortality rate was observed in the cluster including patients with shorter pre-test symptom duration, lower lymphocyte counts, and lower Ct values at diagnosis. The absence of remdesivir administration was associated with worse outcome in the high-mortality cluster (10.5% vs. 36.7%; p < 0.001), comprising subjects with higher viral loads. These results were validated in an external multicenter cohort of 981 patients. CONCLUSIONS: Patients with COVID-19 exhibit varying mortality rates across different clinical phenotypes. K-means clustering aids in identifying patients who derive the greatest mortality benefit from remdesivir use.
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Background: This study aimed to describe documented infections associated with postinfusion fever after CAR T-cell therapy and to evaluate daily changes in vital signs, laboratory results, and the National Early Warning Score (NEWS) in patients with and without confirmed bacterial infections following fever onset, with the objective of assisting in antibiotic stewardship. Methods: This was a retrospective, observational study including all consecutive adult patients who received CAR T-cell therapy. Documented infection in the first fever episode after infusion, and clinical and analytic trend comparison of patients with bacterial documented infections and those without documented infections, are described. Results: Among 152 patients treated with CAR T-cell therapy, 87 (57.2%) had fever within 30 days of infusion, with a median time from infusion to fever of 3 (interquartile range, 2-5) days. Of these 87 patients, 82 (94.3%) received broad-spectrum antibiotics. Infection was documented in 9 (10.3%) patients and only 4 (4.6%) had bacterial infections. Clinical signs and biomarkers were similar in patients with bacterial documented infection and in those without documented infection at fever onset. Fever, tachycardia, and high C-reactive protein levels remained high during the first 3 days after CAR T-cell infusion, even when no infection was documented. Conclusions: Fever is a common symptom following CAR T-cell infusion and is largely treated with broad-spectrum antibiotics. However, confirmed bacterial documented infections after the first fever post-CAR T-cell infusion are very unusual. Because clinical parameters and biomarkers are not useful for identifying infectious fever, other methods should be assessed to ensure the proper use of antibiotics.
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OBJECTIVES: Information is scarce on clinical experiences with non-neutropenic patients with invasive fungal infection (IFI) receiving isavuconazole. We aimed to report the safety and effectiveness of this drug as a first-line treatment or rescue in real life. METHODS: A retrospective, observational multicentric study of non-neutropenic patients who received isavuconazole as an IFI treatment at 12 different university hospitals (January 2018-2022). All patients met criteria for proven, probable or possible IFI according to EORTC-MSG. RESULTS: A total of 238 IFIs were treated with isavuconazole during the study period. Combination therapy was administered in 27.7% of cases. The primary IFI was aspergillosis (217, 91.2%). Other IFIs treated with isavuconazole were candidemia (n = 10), mucormycosis (n = 8), histoplasmosis (n = 2), cryptococcosis (n = 2), and others (n = 4). Median time of isavuconazole treatment was 29 days. Only 5.9% (n = 14) of cases developed toxicity, mainly hepatic-related (10 patients, 4.2%). Nine patients (3.8%) had treatment withdrawn. Successful clinical response at 12 weeks was documented in 50.5% of patients. CONCLUSION: Isavuconazole is an adequate treatment for non-neutropenic patients with IFIs. Toxicity rates were low and its effectiveness was comparable to other antifungal therapies previously reported.