RESUMEN
Immunoglobulins and/or therapeutic antibody preparations are associated with a high rate of false-positive (1,3)-ß-D-glucan (BDG) tests in onco-hematological patients routinely screened for fungal infections. The benefit of BDG monitoring shall be balanced against the risk of false-positive tests leading to unnecessary investigations and costs in this population.
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Glucanos , beta-Glucanos , Humanos , Inmunoglobulinas , Proteoglicanos , Sensibilidad y EspecificidadRESUMEN
PURPOSE: Germline heterozygous mutations of GATA2 underlie a variety of hematological and clinical phenotypes. The genetic, immunological, and clinical features of GATA2-deficient patients with mycobacterial diseases in the familial context remain largely unknown. METHODS: We enrolled 15 GATA2 index cases referred for mycobacterial disease. We describe their genetic and clinical features including their relatives. RESULTS: We identified 12 heterozygous GATA2 mutations, two of which had not been reported. Eight of these mutations were loss-of-function, and four were hypomorphic. None was dominant-negative in vitro, and the GATA2 locus was found to be subject to purifying selection, strongly suggesting a mechanism of haploinsufficiency. Three relatives of index cases had mycobacterial disease and were also heterozygous, resulting in 18 patients in total. Mycobacterial infection was the first clinical manifestation in 11 patients, at a mean age of 22.5 years (range: 12 to 42 years). Most patients also suffered from other infections, monocytopenia, or myelodysplasia. Strikingly, the clinical penetrance was incomplete (32.9% by age 40 years), as 16 heterozygous relatives aged between 6 and 78 years, including 4 older than 60 years, were completely asymptomatic. CONCLUSION: Clinical penetrance for mycobacterial disease was found to be similar to other GATA2 deficiency-related manifestations. These observations suggest that other mechanisms contribute to the phenotypic expression of GATA2 deficiency. A diagnosis of autosomal dominant GATA2 deficiency should be considered in patients with mycobacterial infections and/or other GATA2 deficiency-related phenotypes at any age in life. Moreover, all direct relatives should be genotyped at the GATA2 locus.
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Deficiencia GATA2/diagnóstico , Deficiencia GATA2/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Haploinsuficiencia , Penetrancia , Fenotipo , Adolescente , Adulto , Alelos , Línea Celular , Niño , Análisis Mutacional de ADN , Bases de Datos Genéticas , Femenino , Deficiencia GATA2/epidemiología , Genes Dominantes , Estudios de Asociación Genética/métodos , Genotipo , Mutación de Línea Germinal , Enfermedades Hematológicas/diagnóstico , Enfermedades Hematológicas/etiología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Infecciones por Mycobacterium/diagnóstico , Infecciones por Mycobacterium/etiología , Evaluación de Resultado en la Atención de Salud , Linaje , Secuenciación del Exoma , Adulto JovenRESUMEN
To determine the distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) respiratory viral loads (VL) during the acute phase of infection and their correlation with clinical presentation and inflammation-related biomarkers. Nasopharyngeal swabs from 453 adult SARS-CoV-2-infected patients from the Department of Infectious Diseases, Besançon, France, were collected at the time of admission or consultation for reverse transcriptase polymerase chain reaction (RT-PCR) analysis. Clinical information and concentrations of biological parameters (C-reactive protein [CRP], fibrinogen, lactate dehydrogenase [LDH], prealbumin) were noticed. Mean respiratory VL homogeneously decreased from 7.2 log10 copies/ml (95% confidence interval [CI]: 6.6-7.8) on the first day of symptoms until 4.6 log10 copies/ml (95% CI: 3.8-5.4) at day 10 (slope = -0.24; R2 = .95). VL were poorly correlated with COVID-19 symptoms and outcome, excepted for dyspnea and anosmia, which were significantly associated with lower VL (p < .05). CRP, fibrinogen, and LDH concentrations significantly increased over the first 10 days (median CRP concentrations from 36.8 mg/L at days 0-1 to 99.5 mg/L at days 8-10; p < .01), whereas prealbumin concentrations tended to decrease. Since SARS-CoV-2 respiratory VL regularly decrease in the acute phase of infection, determining the level of VL may help predicting the onset of virus shedding in a specific patient. However, the role of SARS-CoV-2 VL as a biomarker of severity is limited.
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Prueba de COVID-19/métodos , COVID-19/diagnóstico , COVID-19/epidemiología , Carga Viral/métodos , Adulto , Anciano , Anciano de 80 o más Años , Anosmia/patología , Proteína C-Reactiva/análisis , Disnea/patología , Femenino , Fibrinógeno/análisis , Francia/epidemiología , Humanos , L-Lactato Deshidrogenasa/sangre , Masculino , Persona de Mediana Edad , Nasofaringe/virología , Prealbúmina/análisis , ARN Viral/análisis , SARS-CoV-2 , Resultado del Tratamiento , Esparcimiento de Virus , Adulto JovenRESUMEN
The objective of this study was to identify predictive factors of mortality in older adults with coronavirus disease 2019 (COVID-19), including the level of clinical frailty by using the clinical frailty scale (CFS). We analyzed medical records of all patients aged of 75 and older with a confirmed diagnosis of COVID-19 hospitalized in our Hospital between March 3 and April 25, 2020. Standardized variables were prospectively collected, and standardized care were provided to all patients. One hundred and eighty-six patients were included (mean 85.3 ± 5.78 year). The all cause 30-day mortality was 30% (56/186). At admission, dead patients were more dyspneic (57% vs. 38%, p = .014), had more often an oxygen saturation less than 94% (70% vs. 47%, p < .01) and had more often a heart rate faster than 90/min (70% vs. 42%, p < .001). Mortality increased in parallel with CFS score (p = .051) (20 deaths (36%) in 7-9 category). In multivariate analysis, CFS score (odds ratio [OR] = 1.49; confidence interval [CI] 95%, 1.01-2.19; p = .046), age (OR = 1.15; CI 95%, 1.01-1.31; p = .034), and dyspnea (OR = 5.37; CI 95%, 1.33-21.68; p = .018) were associated with all-cause 30-day mortality. It is necessary to integrate the assessment of frailty to determine care management plan of older patients with COVID-19, rather than the only restrictive criterion of age.
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COVID-19/mortalidad , Fragilidad/mortalidad , Anciano , Anciano de 80 o más Años , Femenino , Francia/epidemiología , Mortalidad Hospitalaria , Hospitalización , Humanos , Tiempo de Internación , Masculino , Mortalidad , SARS-CoV-2/aislamiento & purificaciónRESUMEN
OBJECTIVE: The aim of this study was to define whether rapidly reallocating health care workers not experienced with PP for performing PP in ICU is feasible and safe. SUMMARY BACKGROUND DATA: In the setting of severe acute respiratory distress syndrome (ARDS), the use of prone and supine positioning procedures (PP) has been associated with improved oxygenation resulting in decreased mortality. Nevertheless, applying PP is time consuming for ICU staffs that are at risk of mental of physical exhaustion, especially with the constant surge of admitted COVID-19 patients with severe ARDS. METHODS: This prospective cohort study conducted at a single regional university hospital between March 27 and April 15, 2020. Among 117 patients admitted to ICU, 67 patients (57.3%) presented with proven SARS-CoV-2 infection with severe ARDS requiring PP. After accelerated simulation training, 109 volunteers including surgeons, physicians, nurses and physiotherapists, multiple dedicated teams performed daily multiple PP following a systematic checklist. Patient demographics and PP data were collected. Patient safety and health care workers safety were assessed. RESULTS: Among 117 patients admitted to ICU, 67 patients (57.3%) required PP. Overall, 53 (79%) were male, with a median age of 68.5 years and median body mass index of 29.3âkg/m. A total of 384 PP were performed. Overall, complication occurred in 34 PP (8.8%) and led to PP cancelation in 4 patients (1%). Regarding health care workers safety, four health care workers presented with potential COVID-19 related symptoms and none was positive. CONCLUSIONS: To overcome the surge of critically ill COVID-19 patients, reallocating health care workers to targeted medical tasks beyond their respective expertise such as PP was safe.
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COVID-19/complicaciones , Fuerza Laboral en Salud/organización & administración , Posicionamiento del Paciente/métodos , Posición Prona , SARS-CoV-2 , Síndrome Respiratorio Agudo Grave/terapia , Síndrome Respiratorio Agudo Grave/virología , Procedimientos Quirúrgicos Operativos , Anciano , COVID-19/epidemiología , Lista de Verificación , Brotes de Enfermedades , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Asignación de Recursos/métodos , Asignación de Recursos/organización & administraciónRESUMEN
PCR-based viral RNA to confirm the diagnosis of SARS-CoV-2 infection has a sensitivity of around 70%. We report three cases of patients with negative initial PCR and CT scan lesions that led us to suspect COVID-19, but which one(s) are really COVID-19?
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COVID-19/diagnóstico , COVID-19/virología , SARS-CoV-2/genética , Tomografía Computarizada por Rayos X , Corticoesteroides/uso terapéutico , Adulto , Anciano , Biomarcadores , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , ARN Viral , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento , Tratamiento Farmacológico de COVID-19RESUMEN
Importance: Antibiotic overuse drives antibiotic resistance. Gram-negative bacteremia is a common infection that results in substantial antibiotic use. Objective: To compare the clinical effectiveness of C-reactive protein (CRP)-guided, 7-day, and 14-day antibiotic durations 30, 60, and 90 days after treatment initiation. Design, Setting, and Participants: Multicenter, noninferiority, point-of-care randomized clinical trial including adults hospitalized with gram-negative bacteremia conducted in 3 Swiss tertiary care hospitals between April 2017 and May 2019, with follow-up until August 2019. Patients and physicians were blinded between randomization and antibiotic discontinuation. Adults (aged ≥18 years) were eligible for randomization on day 5 (±1 d) of microbiologically efficacious therapy for fermenting, gram-negative bacteria in blood culture(s) if they were afebrile for 24 hours without evidence for complicated infection (eg, abscess) or severe immunosuppression. Intervention: Randomization in a 1:1:1 ratio to an individualized CRP-guided antibiotic treatment duration (discontinuation once CRP declined by 75% from peak; n = 170), fixed 7-day treatment duration (n = 169), or fixed 14-day treatment duration (n = 165). Main Outcomes and Measures: The primary outcome was the clinical failure rate at day 30, defined as the presence of at least 1 of the following, with a non-inferiority margin of 10%: recurrent bacteremia, local suppurative complication, distant complication (growth of the same organism causing the initial bacteremia), restarting gram-negative-directed antibiotic therapy due to clinical worsening suspected to be due to the initial organism, or death due to any cause. Secondary outcomes included the clinical failure rate on day 90 of follow-up. Results: Among 504 patients randomized (median [interquartile range] age, 79 [68-86] years; 306 of 503 [61%] were women), 493 (98%) completed 30-day follow-up and 448 (89%) completed 90-day follow-up. Median antibiotic duration in the CRP group was 7 (interquartile range, 6-10; range, 5-28) days; 34 of the 164 patients (21%) who completed the 30-day follow-up had protocol violations related to treatment assignment. The primary outcome occurred in 4 of 164 (2.4%) patients in the CRP group, 11 of 166 (6.6%) in the 7-day group, and 9 of 163 (5.5%) in the 14-day group (difference in CRP vs 14-day group, -3.1% [1-sided 97.5% CI, -∞ to 1.1]; P < .001; difference in 7-day vs 14-day group, 1.1% [1-sided 97.5% CI, -∞ to 6.3]; P < .001). By day 90, clinical failure occurred in 10 of 143 patients (7.0%) in the CRP group, 16 of 151 (10.6%) in the 7-day group, and 16 of 153 (10.5%) in the 14-day group. Conclusions and Relevance: Among adults with uncomplicated gram-negative bacteremia, 30-day rates of clinical failure for CRP-guided antibiotic treatment duration and fixed 7-day treatment were noninferior to fixed 14-day treatment. However, interpretation is limited by the large noninferiority margin compared with the low observed event rate, as well as low adherence and wide range of treatment durations in the CRP-guided group. Trial Registration: ClinicalTrials.gov Identifier: NCT03101072.
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Antibacterianos/administración & dosificación , Bacteriemia/tratamiento farmacológico , Duración de la Terapia , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Algoritmos , Antibacterianos/efectos adversos , Bacteriemia/microbiología , Bacteriemia/mortalidad , Proteína C-Reactiva/análisis , Esquema de Medicación , Femenino , Bacterias Gramnegativas , Infecciones por Bacterias Gramnegativas/mortalidad , Humanos , Análisis de Intención de Tratar , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Análisis Multivariante , Recurrencia , Análisis de Regresión , Insuficiencia del TratamientoRESUMEN
Invasive aspergillosis (IA) is a life-threatening infection affecting haematological cancer patients with chemotherapy-induced neutropenia. The diagnosis of IA often relies on the detection of galactomannan (GM) in serum or bronchoalveolar lavage fluid (BAL). Bi-weekly serum GM screening has been proposed for a pre-emptive therapeutic approach of IA in patients not receiving mold-active prophylaxis. We have analysed all IA cases among patients with haematological malignancies and prolonged chemotherapy-induced neutropenia (>14 days) in our institution over a 10-year period (2007-2017). Serum GM was measured twice weekly and mold-active prophylaxis was not routinely administered. Thirty IA cases were observed and a positive serum GM was the first indicator of IA in 10 (33%) of them, which represents a need of approximately 500 GM tests for the detection of a single IA case. In the other 20 (67%) cases, suggestive chest CT lesion was the first sign of IA and bronchoscopy was required in 15 (50%) cases with negative serum GM for establishing the diagnosis of probable/proven IA. A positive serum GM was associated with a worse prognosis (57% 12-week survival vs 100% among serum GM-negative patients, P = .006), irrespective of the timing of GM positivity compared to CT. We concluded that bi-weekly serum GM screening demonstrated limited benefit in this population.
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Neoplasias Hematológicas/complicaciones , Aspergilosis Pulmonar Invasiva/diagnóstico , Mananos/sangre , Adulto , Anciano , Aspergillus/genética , Aspergillus/aislamiento & purificación , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/microbiología , Femenino , Galactosa/análogos & derivados , Neoplasias Hematológicas/microbiología , Humanos , Aspergilosis Pulmonar Invasiva/epidemiología , Aspergilosis Pulmonar Invasiva/microbiología , Masculino , Persona de Mediana Edad , Neutropenia/complicaciones , Reacción en Cadena de la Polimerasa , Pronóstico , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Invasive infections of the central nervous system (CNS) or digestive tract caused by commensal fungi of the genus Candida are rare and life-threatening. The known risk factors include acquired and inherited immunodeficiencies, with patients often displaying a history of multiple infections. Cases of meningoencephalitis, colitis, or both caused by Candida species remain unexplained. OBJECTIVE: We studied 5 previously healthy children and adults with unexplained invasive disease of the CNS, digestive tract, or both caused by Candida species. The patients were aged 39, 7, 17, 37, and 26 years at the time of infection and were unrelated, but each was born to consanguineous parents of Turkish (2 patients), Iranian, Moroccan, or Pakistani origin. Meningoencephalitis was reported in 3 patients, meningoencephalitis associated with colitis was reported in a fourth patient, and the fifth patient had colitis only. METHODS: Inherited caspase recruitment domain family, member 9 (CARD9) deficiency was recently reported in otherwise healthy patients with other forms of severe disease caused by Candida, Trichophyton, Phialophora, and Exophiala species, including meningoencephalitis but not colitis caused by Candida and Exophiala species. Therefore we sequenced CARD9 in the 5 patients. RESULTS: All patients were found to be homozygous for rare and deleterious mutant CARD9 alleles: R70W and Q289* for the 3 patients with Candida albicans-induced meningoencephalitis, R35Q for the patient with meningoencephalitis and colitis caused by Candida glabrata, and Q295* for the patient with Candida albicans-induced colitis. Regardless of their levels of mutant CARD9 protein, the patients' monocyte-derived dendritic cells responded poorly to CARD9-dependent fungal agonists (curdlan, heat-killed C albicans, Saccharomyces cerevisiae, and Exophiala dermatitidis). CONCLUSION: Invasive infections of the CNS or digestive tract caused by Candida species in previously healthy children and even adults might be caused by inherited CARD9 deficiency.
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Proteínas Adaptadoras de Señalización CARD/genética , Candidiasis Invasiva/genética , Sistema Nervioso Central/patología , Colitis/genética , Tracto Gastrointestinal/patología , Meningoencefalitis/genética , Adolescente , Adulto , Proteínas Adaptadoras de Señalización CARD/deficiencia , Proteínas Adaptadoras de Señalización CARD/inmunología , Candida/inmunología , Candidiasis Invasiva/inmunología , Candidiasis Invasiva/microbiología , Candidiasis Invasiva/patología , Sistema Nervioso Central/inmunología , Sistema Nervioso Central/microbiología , Niño , Colitis/inmunología , Colitis/microbiología , Colitis/patología , Consanguinidad , Femenino , Tracto Gastrointestinal/inmunología , Tracto Gastrointestinal/microbiología , Expresión Génica , Sitios Genéticos , Estudio de Asociación del Genoma Completo , Homocigoto , Humanos , Masculino , Meningoencefalitis/inmunología , Meningoencefalitis/microbiología , Meningoencefalitis/patología , Linaje , Análisis de Secuencia de ADNRESUMEN
Total joint replacement comes with a high success rate and has been shown to have a very positive impact on our patients suffering from arthritis. Against all efforts about 2 % of our patients will suffer an implant related infection. As the treatment of infected arthroplasties is difficult and expensive the knowledge of risk factors is becoming more and more important for the treatment team in order to improve our preventive measures. Prevention must be performed pre-, intra- and postoperatively. Preoperative optimization of blood sugar levels, nutritional status and correction of general anaemia for example are paramount and the general practitioner as well as the surgeon should be aware of these and other modifiable risk factors in order to operate on the patient in the best possible conditions.
La chirurgie prothétique est une chirurgie dont l'impact est extrêmement favorable pour nos patients souffrant d'une arthrose. Malgré des progrès considérables pour diminuer le taux d'infections postopératoires, cette complication grave survient dans encore environ 2 % des cas. La prévention joue un rôle très important pour diminuer l'incidence de ces infections, à la fois en pré, péri et postopératoire. Le chirurgien et le médecin traitant doivent connaître, rechercher et prendre en charge les facteurs de risque connus d'infection avant toute chirurgie orthopédique. Les principaux facteurs de risque souvent modifiables comme les hyperglycémies, les anémies et la dénutrition seront discutés dans cet article.
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Artroplastia de Reemplazo/métodos , Médicos Generales/organización & administración , Infecciones Relacionadas con Prótesis/prevención & control , Anemia/terapia , Artroplastia de Reemplazo/efectos adversos , Humanos , Procedimientos Ortopédicos/efectos adversos , Procedimientos Ortopédicos/métodos , Rol del Médico , Infecciones Relacionadas con Prótesis/etiología , Factores de RiesgoRESUMEN
During testing for Staphylococcus aureus in an intensive care unit in France in 2011, we found that methicillin-sensitive S. aureus clonal complex 398 was the most frequent clone (29/125, 23.2%). It was isolated from patients (5/89, 5.6%), health care workers (2/63, 3.2%), and environmental sites (15/864, 1.7%). Results indicate emergence of this clone in a hospital setting.
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Infección Hospitalaria , Unidades de Cuidados Intensivos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/microbiología , ADN Bacteriano , Francia/epidemiología , Genes Bacterianos , Genotipo , Humanos , Staphylococcus aureus Resistente a Meticilina/clasificación , Staphylococcus aureus Resistente a Meticilina/genética , Tipificación de Secuencias Multilocus , Neumonía Estafilocócica/epidemiología , Neumonía Estafilocócica/microbiología , Prevalencia , Estudios Prospectivos , Factores de Virulencia/genéticaRESUMEN
INTRODUCTION: Some patients with unexplained neurological symptoms sought care for presumed Lyme neuroborreliosis (LNB). We aimed to compare patients' characteristics with and without LNB. MATERIAL AND METHODS: All patients consulting for LNB suspicion and having a lumbar puncture between 2014 and 2020 in a high endemic area of Lyme borreliosis were included in the study. RESULTS: One hundred fifty-five patients were included. Forty-five patients (29 %) had LNB (mean age: 57.6 years, 28.9 % of women) including 17 with isolated intrathecal synthesis. One hundred and ten patients had no LNB (mainly neurological (29 %) and rheumatological diseases (19 %)). Non-neurological symptoms were similar in patients with LNB and patients with no LNB (asthenia, 31 % vs. 46 %, p = 0.14, arthralgia 20 % vs. 31 %, p = 0.14) with the exception of myalgia, which was less frequent in patients with LNB (4.4 % vs. 19.1 % p = 0.02). In multivariable analysis, factors associated with LNB were presence of facial nerve palsy (OR = 5.7), radiculopathy (OR = 11.3), positive Lyme serology (OR = 5.4) and duration of symptoms less than 3 months (OR = 4.48). Patients with isolated intrathecal synthesis had a longer duration of symptoms (3 vs 1 months) than patients with pleocytosis. Asthenia (5.9 % vs. 32.1 %), headaches (0 % vs. 39.3 %) neuropathic pain (17.6 % vs. 50 %) and facial palsy (11.8 % vs. 39.3 %) were less frequent in patients with isolated intrathecal synthesis than patients with pleocytosis. The presence of isolated subjective neurological symptoms (paresthesia, memory disorders, insomnia, irritability, asthenia, headaches) was reported in 7/17 (41 %) of patients with isolated intrathecal synthesis, 2/28 (7.1 %) in patients with pleocytosis and 75/110 (68 %) in patients without LNB (p < 0.001). CONCLUSION: More than one quarter of patients consulted for suspected LNB had non-neurologic symptoms, whether or not they have a LNB. Concerning patients with isolated intrathecal synthesis, the question of presence of sequelae with a spontaneously cured disease or an active Lyme borreliosis requiring antibiotic remain.
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Enfermedades Endémicas , Neuroborreliosis de Lyme , Humanos , Neuroborreliosis de Lyme/epidemiología , Neuroborreliosis de Lyme/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Adulto , Radiculopatía/epidemiologíaRESUMEN
This large, multicenter, retrospective cohort study including onco-hematological neutropenic patients with Pseudomonas aeruginosa bloodstream infection (PABSI) found that among 1213 episodes, 411 (33%) presented with septic shock. The presence of solid tumors (33.3% vs. 20.2%, p < 0.001), a high-risk Multinational Association for Supportive Care in Cancer (MASCC) index score (92.6% vs. 57.4%; p < 0.001), pneumonia (38% vs. 19.2% p < 0.001), and infection due to multidrug-resistant P. aeruginosa (MDRPA) (33.8% vs. 21.1%, p < 0.001) were statistically significantly higher in patients with septic shock compared to those without. Patients with septic shock were more likely to receive inadequate empirical antibiotic therapy (IEAT) (21.7% vs. 16.2%, p = 0.020) and to present poorer outcomes, including a need for ICU admission (74% vs. 10.5%; p < 0.001), mechanical ventilation (49.1% vs. 5.6%; p < 0.001), and higher 7-day and 30-day case fatality rates (58.2% vs. 12%, p < 0.001, and 74% vs. 23.1%, p < 0.001, respectively). Risk factors for 30-day case fatality rate in patients with septic shock were orotracheal intubation, IEAT, infection due to MDRPA, and persistent PABSI. Therapy with granulocyte colony-stimulating factor and BSI from the urinary tract were associated with improved survival. Carbapenems were the most frequent IEAT in patients with septic shock, and the use of empirical combination therapy showed a tendency towards improved survival. Our findings emphasize the need for tailored management strategies in this high-risk population.
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Anemia Refractaria con Exceso de Blastos , Aspergilosis/genética , Proteína C-Reactiva/genética , Leucemia Mieloide Aguda , Proteínas de Neoplasias/genética , Polimorfismo de Nucleótido Simple , Leucemia-Linfoma Linfoblástico de Células Precursoras , Componente Amiloide P Sérico/genética , Adulto , Anemia Refractaria con Exceso de Blastos/tratamiento farmacológico , Anemia Refractaria con Exceso de Blastos/genética , Anemia Refractaria con Exceso de Blastos/microbiología , Aspergilosis/inducido químicamente , Femenino , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/microbiología , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/microbiologíaRESUMEN
We investigated single nucleotide polymorphisms (SNPs) possibly involved in immune reconstitution inflammatory syndrome of chronic disseminated candidiasis (IRIS-CDC) through a candidate gene approach and a prospective matched-control study. We found that an SNP located in interleukin-1B at rs1143627 was significantly associated with the risk of developing IRIS-CDC.
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Candida tropicalis is the Candida species that is mostly involved in case of acute disseminated candidiasis. We report here a case with whole body dissemination (pulmonary, cutaneous, muscular, hepatic, spinal and cerebral) highlighted by impressive imagery obtained by positron emission tomography scanner in a patient treated for T cell acute lymphocytic leukemia.
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Candidiasis , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Candida , Candida tropicalis , Candidiasis/complicaciones , Candidiasis/diagnóstico , Candidiasis/patología , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/complicacionesRESUMEN
Objectives: To assess the clinical features and outcomes of Pseudomonas aeruginosa bloodstream infection (PA BSI) in neutropenic patients with hematological malignancies (HM) and with solid tumors (ST), and identify the risk factors for 30-day mortality. Methods: We performed a large multicenter, retrospective cohort study including onco-hematological neutropenic patients with PA BSI conducted across 34 centers in 12 countries (January 2006−May 2018). Episodes occurring in hematologic patients were compared to those developing in patients with ST. Risk factors associated with 30-day mortality were investigated in both groups. Results: Of 1217 episodes of PA BSI, 917 occurred in patients with HM and 300 in patients with ST. Hematological patients had more commonly profound neutropenia (0.1 × 109 cells/mm) (67% vs. 44.6%; p < 0.001), and a high risk Multinational Association for Supportive Care in Cancer (MASCC) index score (32.2% vs. 26.7%; p = 0.05). Catheter-infection (10.7% vs. 4.7%; p = 0.001), mucositis (2.4% vs. 0.7%; p = 0.042), and perianal infection (3.6% vs. 0.3%; p = 0.001) predominated as BSI sources in the hematological patients, whereas pneumonia (22.9% vs. 33.7%; p < 0.001) and other abdominal sites (2.8% vs. 6.3%; p = 0.006) were more common in patients with ST. Hematological patients had more frequent BSI due to multidrug-resistant P. aeruginosa (MDRPA) (23.2% vs. 7.7%; p < 0.001), and were more likely to receive inadequate initial antibiotic therapy (IEAT) (20.1% vs. 12%; p < 0.001). Patients with ST presented more frequently with septic shock (45.8% vs. 30%; p < 0.001), and presented worse outcomes, with increased 7-day (38% vs. 24.2%; p < 0.001) and 30-day (49% vs. 37.3%; p < 0.001) case-fatality rates. Risk factors for 30-day mortality in hematologic patients were high risk MASCC index score, IEAT, pneumonia, infection due to MDRPA, and septic shock. Risk factors for 30-day mortality in patients with ST were high risk MASCC index score, IEAT, persistent BSI, and septic shock. Therapy with granulocyte colony-stimulating factor was associated with survival in both groups. Conclusions: The clinical features and outcomes of PA BSI in neutropenic cancer patients showed some differences depending on the underlying malignancy. Considering these differences and the risk factors for mortality may be useful to optimize their therapeutic management. Among the risk factors associated with overall mortality, IEAT and the administration of granulocyte colony-stimulating factor were the only modifiable variables.
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To assess the effect of combination antibiotic empirical therapy on 30-day case-fatality rate in neutropenic cancer patients with Pseudomonas aeruginosa (PA) bacteremic pneumonia. This was a multinational, retrospective cohort study of neutropenic onco-hematological patients with PA bloodstream infection (BSI) (2006−2018). The effect of appropriate empirical combination therapy, appropriate monotherapy and inappropriate empirical antibiotic therapy [IEAT] on 30-day case-fatality was assessed only in patients with PA bacteremic pneumonia. Among 1017 PA BSI episodes, pneumonia was the source of BSI in 294 (28.9%). Among those, 52 (17.7%) were caused by a multidrug-resistant (MDR) strain and 68 (23.1%) received IEAT, mainly when the infection was caused by an MDR strain [38/52 (73.1%) vs. 30/242 (12.4%); p < 0.001]. The 30-day case-fatality rate was higher in patients with PA bacteremic pneumonia than in those with PA BSI from other sources (55.1% vs. 31.4%; p < 0.001). IEAT was associated with increased 30-day case-fatality (aHR 1.44 [95%CI 1.01−2.03]; p = 0.042), whereas the use of appropriate combination empirical treatment was independently associated with improved survival (aHR 0.46 [95%CI 0.27−0.78]; p = 0.004). Appropriate empirical monotherapy was not associated with improved overall survival (aHR 1.25 [95%CI 0.76−2.05]; p = 0.39). Combination antibiotic empirical therapy should be administered promptly in febrile neutropenic patients with suspected pneumonia as the source of infection.
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INTRODUCTION: COVID-19 vaccination seems to be the most pertinent pharmacologic public health measure to control the pandemic. Reactogenicity symptoms were frequent in vaccine recipients mostly mild to moderate and commonly reported after the second dose. However, there is a lack of data in patients with a previous diagnosis of Covid-19. METHODS: We analysed side effects of 311 patients after the first dose of Pfizer-BioNTech COVID-19 vaccine, in a french university hospital. We compared patients with COVID-19 history to naive individuals. All the data collected are based on self-reported, including COVID-19 exposure status. RESULTS: Overall, 229 (74%) patients reported at least one side effect. Among participants with history of Covid-19, 95% reported at least one adverse event versus 70% in naive patients (p < 0.01). However, symptom intensity was not different between the 2 groups. CONCLUSION: Vaccine recipients with prior COVID-19 reported more, but no more serious, side effects than naive participants.
Asunto(s)
COVID-19 , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Vacunas contra la COVID-19 , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Humanos , Pandemias , SARS-CoV-2RESUMEN
INTRODUCTION: Immunocompromised patients are at high-risk for severe influenza and invasive pneumococcal diseases (IPD). Despite the French Public Health Council (FPHC) and the 7th European Conference on Infections in Leukaemia (ECIL7) recommendations, vaccination coverage remains insufficient. This study aimed to estimate the coverage and determinants of influenza, pneumococcal and diphtheria-tetanus-poliomyelitis (dTP) vaccinations in hematological patients underlying chemotherapy. METHODS: A survey was distributed to all patients of the hematology day hospital assessing vaccine uptakes and general opinion about vaccination. Vaccine uptakes were collected from medical and vaccination records; knowledge of and attitudes towards vaccinations in immunocompromised patients were evaluated for each general practitioner (GP) by phone call. Adequacy between vaccine uptakes and indication or not to vaccinate according to ECIL7 guidelines was assessed. Factors associated with vaccine uptakes were assessed by multivariate logistic regression. RESULTS: Among 145 patients, 66 % were aged 65 years or older, 40 % were followed for lymphoma and 38 % for multiple myeloma, 39 % were treated with anti-CD20 antibodies. Vaccination coverage was suboptimal for influenza (45-56 %), dTP (44 %) and IPD (16-19 %) regardless of the guidelines followed, with a wide variation in rates by information source (19-76 %). Adequacy rate with ECIL7 recommendations were 63 % and 87 % for influenza and IPD respectively. Information of patients on specific vaccinations was positively associated with flu and IPD vaccinations, as well as favorable attitude toward vaccination and age ≥ 65 years for flu vaccination, and recommendation by hematologist for pneumococcal vaccination. CONCLUSION: Despite vaccination opportunities, the complexity of these specific recommendations and the lack of communication between the health actors could explain the suboptimal vaccination coverage in this high-risk population. A proactive attitude of all actors in the city and hospital, including better patient information and a personalized and evolving vaccination schedule to help GPs to coordinate vaccination would allow to improve vaccine coverage.