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1.
Ann Surg ; 277(5): e1157-e1163, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-35417113

RESUMEN

OBJECTIVES: The present study aimed to assess whether high-risk American Society of Anesthesiologists (ASA)-Physical Status was an independent risk factor for the development of surgical site infection (SSI) after infra-inguinal lower extremity bypass (LEB). SUMMARY OF BACKGROUND DATA: The ASA-Physical Status Classification System assesses the overall physical status preoperatively. ASA-Physical Status is associated with postoperative morbidity and mortality. However, limited data are available on how ASA-Physical Status Class affects the development of SSI after infra-inguinal LEB. METHODS: Patients who had undergone infra-inguinal LEB from January 1, 2015 to December 31, 2018, for obliterative arteriopathy or popliteal aneurysm at our university hospital were included. SSI risk factors were identified using multivariable logistic regression. The length of hospital stay, major limb events (MALE), major adverse cardiovascular events (MACE), and all-cause mortality were compared for patients with SSI versus those without SSI 3 months and 1- year of follow-up after the index surgery. RESULTS: Among the 267 patients included, 30 (11.2%) developed SSI during the 3-month period and 32 (12%) at 1 year. ASA-Physical Status ≥3 [odds ratio (OR): 3.7, 95% confidence interval CI) 1.5-11.1], emergency surgery (OR: 2.7, 95% CI 1.2-6.0), general anesthesia (OR: 2.8, 95% CI 1.3-6.1), and procedure performed by a junior surgeon (OR: 2.7, 95% CI 1.3-6.0) were independently associated with SSI. At 3 months and 1 year, SSI was significantly associated with MALE (including surgical wound debridement, subsequent thrombectomy, major amputation), length of hospital stay, and all-cause mortality. CONCLUSION: The ASA-Physical Status should be considered in medical management when an infra-inguinal LEB is considered in frail patients, to prevent surgical complications.


Asunto(s)
Anestesiólogos , Infección de la Herida Quirúrgica , Humanos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/prevención & control , Factores de Riesgo , Extremidad Inferior/cirugía , Extremidad Inferior/irrigación sanguínea , Estudios Retrospectivos
2.
J Antimicrob Chemother ; 77(9): 2532-2535, 2022 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-35696322

RESUMEN

BACKGROUND: Necrotizing external otitis (NEO) is a severe infection of the skull base that occurs generally in the elderly and/or in diabetic recipients. There are few data in the literature about the therapeutic management of this complex bone infection. OBJECTIVES: To analyse relapses after NEO treatment completion, and to describe the clinical features of NEO. METHODS: We performed a retrospective cohort study in the Lyon regional reference centre for the management of complex bone and joint infections. Consecutive cases of NEO from 1 January 2006 to 31 December 2018 were included. The primary outcome was the relapse of NEO. Variables were analysed using Cox regression survival analysis with adjusted hazard ratio (aHR) and Kaplan-Meier curve. RESULTS: Sixty-six patients were included. Median age was 75 (IQR 69-81) years and 46 (70%) patients were diabetic. Eleven patients (17%) had temporomandibular arthritis, 10 (15%) cranial nerve paralysis, 2 (3%) cerebral thrombophlebitis, and 2 (3%) contiguous abscess. Microbiological documentation was obtained in 56 patients and revealed Pseudomonas aeruginosa in 44/56 patients (79%). Nine (14%) cases had no microbiological documentation. Antibiotic therapy was dual for 63 (95%) patients. During a median follow-up of 27 (IQR 12-40) months, 16 out of 63 (25%) patients experienced a relapse. Fungal infection was significantly associated with relapse [aHR 4.1 (95% CI 1.1-15); P = 0.03]. CONCLUSIONS: NEO is a severe bone infection, mainly (but not exclusively) caused by P. aeruginosa, which occurs in elderly and diabetic recipients. Fungal infections at baseline significantly impact the outcome.


Asunto(s)
Diabetes Mellitus , Osteomielitis , Otitis Externa , Infecciones por Pseudomonas , Anciano , Humanos , Osteomielitis/tratamiento farmacológico , Osteomielitis/microbiología , Otitis Externa/tratamiento farmacológico , Otitis Externa/microbiología , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa , Recurrencia , Estudios Retrospectivos , Factores de Riesgo
3.
Clin Infect Dis ; 73(7): 1223-1230, 2021 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-34009270

RESUMEN

BACKGROUND: Infective endocarditis (IE) is a severe disease requiring microbial identification to successfully adapt its treatment. Currently, identification of its etiological microorganism remains unresolved in 5.2% of cases. We aimed to improve IE diagnosis using an ultra-sensitive molecular technique on cardiac samples in microbiologically nondocumented (culture and conventional polymerase chain reaction [PCR]) IE (NDIE) cases. METHODS: Cardiac samples explanted in a tertiary hospital in Lyon, France, from patients with definite IE over a 5-year period were retrospectively analyzed. NDIE was defined as Duke definite-IE associated with negative explorations including cardiac samples culture, bacterial amplification, and serologies. Ultrasensitive molecular diagnosis was achieved using the Universal Microbe Detection kit (Molzym®). Fungal identification was confirmed using 26S-rDNA and internal transcribed spacer amplifications. Fungal infection was confirmed using Grocott-Gromori staining, auto-immunohistochemistry on cardiac samples, and mannan serologies. RESULTS: Among 88 included patients, microbial DNA was detected in all 16 NDIE cases. Bacterial taxa typical of IE etiologies were detected in 13/16 cases and Malassezia restricta in the 3 other cases. In these 3 cases, histological examination confirmed the presence of fungi pathognomonic of Malassezia that reacted with patient sera in an auto-immunohistochemistry assay and cross-reacted with Candida albicans in an indirect immunofluorescent assay. CONCLUSIONS: M. restricta appears to be an underestimated causative agent of NDIE. Importantly, serological cross-reaction of M. restricta with C. albicans may lead to its misdiagnosis. This is of major concern since M. restricta is intrinsically resistant to echinocandins; the reference treatment for Candida-fungal IE.


Asunto(s)
Endocarditis Bacteriana , Endocarditis , Malassezia , Cultivo de Sangre , Endocarditis/diagnóstico , Válvulas Cardíacas , Humanos , Malassezia/genética , ARN Ribosómico 16S , Estudios Retrospectivos
4.
Clin Infect Dis ; 73(3): 393-403, 2021 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-32488236

RESUMEN

BACKGROUND: Diagnostic and patients' management modifications induced by whole-body 18F-FDG-PET/CT had not been evaluated so far in prosthetic valve (PV) or native valve (NV) infective endocarditis (IE)-suspected patients. METHODS: In sum, 140 consecutive patients in 8 tertiary care hospitals underwent 18F-FDG-PET/CT. ESC-2015-modified Duke criteria and patients' management plan were established jointly by 2 experts before 18F-FDG-PET/CT. The same experts reestablished Duke classification and patients' management plan immediately after qualitative interpretation of 18F-FDG-PET/CT. A 6-month final Duke classification was established. RESULTS: Among the 70 PV and 70 NV patients, 34 and 46 were classified as definite IE before 18F-FDG-PET/CT. Abnormal perivalvular 18F-FDG uptake was recorded in 67.2% PV and 24.3% NV patients respectively (P < .001) and extracardiac uptake in 44.3% PV and 51.4% NV patients. IE classification was modified in 24.3% and 5.7% patients (P = .005) (net reclassification index 20% and 4.3%). Patients' managements were modified in 21.4% PV and 31.4% NV patients (P = .25). It was mainly due to perivalvular uptake in PV patients and to extra-cardiac uptake in NV patients and consisted in surgery plan modifications in 7 patients, antibiotic plan modifications in 22 patients and both in 5 patients. Altogether, 18F-FDG-PET/CT modified classification and/or care in 40% of the patients (95% confidence interval: 32-48), which was most likely to occur in those with a noncontributing echocardiography (P < .001) or IE classified as possible at baseline (P = .04), while there was no difference between NV and PV. CONCLUSIONS: Systematic 18F-FDG-PET/CT did significantly and appropriately impact diagnostic classification and/or IE management in PV and NV-IE suspected patients. CLINICAL TRIALS REGISTRATION: NCT02287792.


Asunto(s)
Endocarditis , Prótesis Valvulares Cardíacas , Endocarditis/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Estudios Prospectivos , Radiofármacos
5.
Clin Chem ; 67(5): 742-752, 2021 04 29.
Artículo en Inglés | MEDLINE | ID: mdl-33399823

RESUMEN

BACKGROUND: The association between SARS-CoV-2 commercial serological assays and virus neutralization test (VNT) has been poorly explored in mild patients with COVID-19. METHODS: 439 serum specimens were longitudinally collected from 76 healthcare workers with RT-PCR-confirmed COVID-19. The clinical sensitivity (determined weekly) of 9 commercial serological assays were evaluated. Clinical specificity was assessed using 69 pre-pandemic sera. Correlation, agreement, and concordance with the VNT were also assessed on a subset of 170 samples. Area under the ROC curve (AUC) was estimated at 2 neutralizing antibody titers. RESULTS: The Wantai Total Ab assay targeting the receptor binding domain (RBD) within the S protein presented the best sensitivity at different times during the course of disease. The clinical specificity was greater than 95% for all tests except for the Euroimmun IgA assay. The overall agreement with the presence of neutralizing antibodies ranged from 62.2% (95%CI; 56.0-68.1) for bioMérieux IgM to 91.2% (87.0-94.2) for Siemens. The lowest negative percent agreement (NPA) was found with the Wantai Total Ab assay (NPA 33% (21.1-48.3)). The NPA for other total Ab or IgG assays targeting the S or the RBD was 80.7% (66.7-89.7), 90.3% (78.1-96.1), and 96.8% (86.8-99.3) for Siemens, bioMérieux IgG, and DiaSorin, respectively. None of the commercial assays have sufficient performance to detect a neutralizing titer of 80 (AUC < 0.76). CONCLUSIONS: Although some assays show a better agreement with VNT than others, the present findings emphasize that commercialized serological tests, including those targeting the RBD, cannot substitute a VNT for the assessment of functional antibody response.


Asunto(s)
Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , COVID-19/diagnóstico , Adulto , Anciano , COVID-19/sangre , Prueba Serológica para COVID-19/métodos , Estudios de Cohortes , Femenino , Humanos , Estudios Longitudinales , Masculino , Pruebas de Neutralización , Estudios Prospectivos , SARS-CoV-2 , Sensibilidad y Especificidad
6.
Crit Care ; 24(1): 434, 2020 07 14.
Artículo en Inglés | MEDLINE | ID: mdl-32665030

RESUMEN

BACKGROUND: Improving timeliness of pathogen identification is crucial to allow early adaptation of antibiotic therapy and improve prognosis in patients with pneumonia. We evaluated the relevance of a new syndromic rapid multiplex PCR test (rm-PCR) on respiratory samples to guide empirical antimicrobial therapy in adult patients with community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and ventilator-acquired pneumonia (VAP). METHODS: This retrospective multicenter study was conducted in four French university hospitals. Respiratory samples were obtained from patients with clinical and radiological signs of pneumonia and simultaneously tested using conventional microbiological methods and the rm-PCR. A committee composed of an intensivist, a microbiologist, and an infectious diseases specialist retrospectively assessed all medical files and agreed on the most appropriate antimicrobial therapy for each pneumonia episode, according to the results of rm-PCR and blinded to the culture results. The rm-PCR-guided antimicrobial regimen was compared to the empirical treatment routinely administered to the patient in standard care. RESULTS: We included 159 pneumonia episodes. Most patients were hospitalized in intensive care units (n = 129, 81%), and episodes were HAP (n = 68, 43%), CAP (n = 54, 34%), and VAP (n = 37, 23%). Conventional culture isolated ≥ 1 microorganism(s) at significant level in 95 (60%) patients. The syndromic rm-PCR detected at least one bacteria in 132 (83%) episodes. Based on the results of the rm-PCR, the multidisciplinary committee proposed a modification of the empirical therapy in 123 (77%) pneumonia episodes. The modification was a de-escalation in 63 (40%), an escalation in 35 (22%), and undetermined in 25 (16%) patients. In microbiologically documented episodes (n = 95), the rm-PCR increased appropriateness of the empirical therapy to 83 (87%), as compared to 73 (77%) in routine care. CONCLUSIONS: Use of a syndromic rm-PCR test has the potential to reduce unnecessary antimicrobial exposure and increase the appropriateness of empirical antibiotic therapy in adult patients with pneumonia.


Asunto(s)
Antiinfecciosos/administración & dosificación , Reacción en Cadena de la Polimerasa Multiplex/métodos , Neumonía/tratamiento farmacológico , Factores de Tiempo , Adulto , Antiinfecciosos/uso terapéutico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neumonía/fisiopatología , Estudios Retrospectivos
8.
J Antimicrob Chemother ; 71(4): 1063-70, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26801082

RESUMEN

OBJECTIVES: The aim of this study was to evaluate pristinamycin in the treatment of MSSA bone and joint infection (BJI). PATIENTS AND METHODS: A retrospective, single-centre cohort study (2001-11) investigated outcome in adults receiving pristinamycin for MSSA BJI and pristinamycin-related adverse events (AEs). RESULTS: One hundred and two MSSA BJIs were assessed in 98 patients [chronic infection, 33.3%; and orthopaedic device-related infection (ODI), 67.6%]. Surgery was performed in 77.5% of total cases, and in all but three ODIs, associated with antibiotic therapy of a median total duration of 29.2 weeks. Pristinamycin was prescribed as a part of the initial intensive treatment phase (29.4%) and/or included in final maintenance therapy (83.3%) at a dose of 47.6 (45.5-52.6) mg/kg/day for 9.3 (1.4-20.4) weeks. AEs occurred in 13.3% of patients, consisting of gastrointestinal disorder (76.9%) or allergic reaction (23.1%), leading to treatment interruption in 11 cases. AEs were related to daily dose (OR, 2.733 for each 10 additional mg/kg/day; P = 0.049). After a follow-up of 76.4 (29.6-146.9) weeks, the failure rate was 34.3%, associated with ODI (OR, 4.421; P = 0.006), particularly when the implant was retained (OR, 4.217; P = 0.007). In most patients, the pristinamycin companion drug was a fluoroquinolone (68.7%) or rifampicin (21.7%), without difference regarding outcome. CONCLUSIONS: Pristinamycin is an effective, well-tolerated alternative therapeutic option in MSSA BJI, on condition that a daily dosage of 50 mg/kg is respected.


Asunto(s)
Antibacterianos/uso terapéutico , Artritis Infecciosa/tratamiento farmacológico , Artritis Infecciosa/microbiología , Enfermedades Óseas Infecciosas/tratamiento farmacológico , Enfermedades Óseas Infecciosas/microbiología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pristinamicina/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , Anciano , Antibacterianos/farmacología , Artritis Infecciosa/mortalidad , Enfermedades Óseas Infecciosas/mortalidad , Estudios de Cohortes , Terapia Combinada , Comorbilidad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pristinamicina/farmacología , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/mortalidad , Resultado del Tratamiento
10.
BMC Infect Dis ; 16(1): 622, 2016 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-27809799

RESUMEN

BACKGROUND: Staphylococci represent the first etiologic agents of bone and joint infection (BJI), leading glycopeptides use, especially in case of methicillin-resistance or betalactam intolerance. Teicoplanin may represent an alternative to vancomycin because of its acceptable bone penetration and possible subcutaneous administration. METHODS: Adults receiving teicoplanin for S. aureus BJI were included in a retrospective cohort study investigating intravenous or subcutaneous teicoplanin safety and pharmacokinetics. RESULTS: Sixty-five S. aureus BJIs (orthopedic device-related infections, 69 %; methicillin-resistance, 17 %) were treated by teicoplanin at the initial dose of 5.7 mg/kg/day (IQR, 4.7-6.5) after a loading dose of 5 injections 12 h apart. The first trough teicoplanin level (Cmin) reached the therapeutic target (15 mg/L) in 26 % of patients, only. An overdose (Cmin >25 mg/L) was observed in 16 % patients, 50 % of which had chronic renal failure (p = 0.049). Seven adverse events occurred in 6 patients (10 %); no predictive factor could be highlighted. After a 91-week follow-up (IQR, 51-183), 27 treatment failures were observed (42 %), associated with diabetes (OR, 5.1; p = 0.057), systemic inflammatory disease (OR, 5.6; p = 0.043), and abscess (OR, 4.1; p < 10-3). A normal CRP-value at 1 month was protective (OR, 0.2; p = 0.029). Subcutaneous administration (n = 14) showed no difference in pharmacokinetics and tolerance compared to the intravenous route. CONCLUSIONS: Teicoplanin constitutes a well-tolerated therapeutic alternative in S. aureus BJI, with a possible subcutaneous administration in outpatients. The loading dose might be increase to 9-12 mg/kg to quickly reach the therapeutic target, but tolerance of such higher doses remains to be evaluated, especially if using the subcutaneous route.


Asunto(s)
Antibacterianos/uso terapéutico , Artritis Infecciosa/tratamiento farmacológico , Prótesis Articulares , Osteomielitis/tratamiento farmacológico , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Infecciones Estafilocócicas/tratamiento farmacológico , Teicoplanina/uso terapéutico , Adulto , Anciano , Artritis Infecciosa/epidemiología , Artritis Infecciosa/microbiología , Comorbilidad , Sobredosis de Droga/epidemiología , Femenino , Humanos , Infusiones Intravenosas , Infusiones Subcutáneas , Fallo Renal Crónico/epidemiología , Masculino , Staphylococcus aureus Resistente a Meticilina , Persona de Mediana Edad , Osteomielitis/epidemiología , Osteomielitis/microbiología , Infecciones Relacionadas con Prótesis/epidemiología , Infecciones Relacionadas con Prótesis/microbiología , Estudios Retrospectivos , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus , Insuficiencia del Tratamiento , Resultado del Tratamiento , Vancomicina/uso terapéutico
12.
Mycopathologia ; 179(1-2): 135-40, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25253233

RESUMEN

Recent literature has shown the growing importance of opportunistic fungal infections due to Fusarium spp. However, disseminated fusariosis remains rare in patients without neutropenia. We report a case of fungaemia in a 78-year-old French woman without definite immunodeficiency. Fusarium proliferatum grew from both central and peripheral blood cultures. Fever was the only clinical sign of the infection. An appropriate antifungal therapy with voriconazole led to the recovery of the patient. An environmental investigation was undertaken but failed to find a reservoir of Fusarium spores. A contaminated central venous catheter might have been the source of fungaemia.


Asunto(s)
Antifúngicos/uso terapéutico , Fusariosis/diagnóstico , Fusariosis/tratamiento farmacológico , Fusarium/efectos de los fármacos , Infecciones Oportunistas/tratamiento farmacológico , Anciano , Artroplastia de Reemplazo de Cadera/efectos adversos , Infecciones Relacionadas con Catéteres/diagnóstico , Infecciones Relacionadas con Catéteres/tratamiento farmacológico , Infecciones Relacionadas con Catéteres/microbiología , Catéteres Venosos Centrales/microbiología , Femenino , Francia , Fusariosis/microbiología , Humanos , Pruebas de Sensibilidad Microbiana , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/microbiología , Voriconazol/uso terapéutico
13.
Antimicrob Agents Chemother ; 57(1): 517-23, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23147727

RESUMEN

Limited data on the pharmacokinetics and pharmacodynamics (PK/PD) of unboosted atazanavir (uATV) in treatment-experienced patients are available. The aim of this work was to study the PK/PD of unboosted atazanavir in a cohort of HIV-infected patients. Data were available for 58 HIV-infected patients (69 uATV-based regimens). Atazanavir concentrations were analyzed by using a population approach, and the relationship between atazanavir PK and clinical outcome was examined using logistic regression. The final PK model was a linear one-compartment model with a mixture absorption model to account for two subgroups of absorbers. The mean (interindividual variability) of population PK parameters were as follows: clearance, 13.4 liters/h (40.7%), volume of distribution, 71.1 liters (29.7%), and fraction of regular absorbers, 0.49. Seven subjects experienced virological failure after switch to uATV. All of them were identified as low absorbers in the PK modeling. The absorption rate constant (0.38 ± 0.20 versus 0.75 ± 0.28 h(-1); P = 0.002) and ATV exposure (area under the concentration-time curve from 0 to 24 h [AUC(0-24)], 10.3 ± 2.1 versus 22.4 ± 11.2 mg · h · liter(-1); P = 0.001) were significantly lower in patients with virological failure than in patients without failure. In the logistic regression analysis, both the absorption rate constant and ATV trough concentration significantly influenced the probability of virological failure. A significant relationship between ATV pharmacokinetics and virological response was observed in a cohort of HIV patients who were administered unboosted atazanavir. This study also suggests that twice-daily administration of uATV may optimize drug therapy.


Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/farmacocinética , VIH/efectos de los fármacos , Oligopéptidos/farmacocinética , Piridinas/farmacocinética , Adulto , Área Bajo la Curva , Sulfato de Atazanavir , Disponibilidad Biológica , Esquema de Medicación , Femenino , VIH/crecimiento & desarrollo , Infecciones por VIH/virología , Inhibidores de la Proteasa del VIH/sangre , Inhibidores de la Proteasa del VIH/farmacología , Humanos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Oligopéptidos/sangre , Oligopéptidos/farmacología , Piridinas/sangre , Piridinas/farmacología , Insuficiencia del Tratamiento
14.
Med Mycol Case Rep ; 37: 19-22, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35770129

RESUMEN

Immunosuppression is a major feature of septic shock and patients are at increased risk for opportunistic infections. We describe a successful use of immunostimulation to treat mixed mould and bacterial superinfection in a previously healthy 38-year-old female patient admitted for severe extensive fasciitis. Interferon gamma associated with nivolumab reversed successfully deactivation of immune cells assessed by altered expressions of monocyte human leukocyte antigen-DR (HLA-DR) and lymphocyte programmed death receptor-1 (PD-1). Immunosuppressed patients in ICU with invasive bacterial and fungal infections may benefit from immunostimulation.

15.
Front Immunol ; 13: 883638, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36072605

RESUMEN

Background: Mucormycosis is a deadly fungal infection that mainly affects severely immunocompromised patients. We report herein the case of a previously immunocompetent adult woman who developed invasive cutaneous mucormycosis after severe burn injuries. Interferon-gamma (IFN-γ) treatment was added after failure of conventional treatment and confirmation of a sustained profound immunodepression. The diagnosis was based on a reduced expression of HLA-DR on monocytes (mHLA-DR), NK lymphopenia and a high proportion of immature neutrophils. The immune-related alterations were longitudinally monitored using panels of immune-related biomarkers. Results: Initiation of IFN-γ was associated with a rapid clinical improvement and a subsequent healing of mucormycosis infection, with no residual fungi at the surgical wound repair. The serial immunological assessment showed sharp improvements of immune parameters: a rapid recovery of mHLA-DR and of transcriptomic markers for T-cell proliferation. The patient survived and was later discharged from the ICU. Conclusion: The treatment with recombinant IFN-γ participated to the resolution of a progressively invasive mucormycosis infection, with rapid improvement in immune parameters. In the era of precision medicine in the ICU, availability of comprehensive immune monitoring tools could help guiding management of refractory infections and provide rationale for immune stimulation strategies in these high risk patients.


Asunto(s)
Quemaduras , Mucormicosis , Adulto , Quemaduras/complicaciones , Terapia Combinada , Femenino , Antígenos HLA-DR , Humanos , Interferón gamma/uso terapéutico , Mucormicosis/diagnóstico , Mucormicosis/tratamiento farmacológico , Mucormicosis/etiología , Proteínas Recombinantes
16.
Endosc Int Open ; 10(4): E328-E341, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35433214

RESUMEN

Background and study aims Perforations are a known adverse event of endoscopy procedures; a proposal for appropriate management should be available in each center as recommended by the European Society of Gastrointestinal Endoscopy. The objective of this study was to establish a charter for the management of endoscopic perforations, based on local evidence. Patients and methods Patients were included if they experienced partial or complete perforation during an endoscopic procedure between 2008 and 2018 (retrospectively until 2016, then prospectively). Perforations (size, location, closure) and management (imagery, antibiotics, surgery) were analyzed. Using these results, a panel of experts was asked to propose a consensual management charter. Results A total of 105 patients were included. Perforations occurred mainly during therapeutic procedures (91, 86.7%). Of the perforations, 78 (74.3 %) were diagnosed immediately and managed during the procedure; 69 of 78 (88.5 %) were successfully closed. Closures were more effective during therapeutic procedures (60 of 66, 90.9 %) than during diagnostic procedures (9 of 12, 75.0 %, P  = 0.06). Endoscopic closure was effective for 37 of 38 perforations (97.4 %) < 0.5 cm, and for 26 of 34 perforations (76.5 %) ≥ 0.5 cm ( P  < 0.05). For perforations < 0.5 cm, systematic computed tomography (CT) scan, antibiotics, or surgical evaluation did not improve the outcome. Four of 105 deaths (3.8 %) occurred after perforation, one of which was attributable to the perforation itself. Conclusions Detection and closure of perforations during endoscopic procedure had a better outcome compared to delayed perforations; perforations < 0.5 cm had a very good prognosis and CT scan, surgeon evaluation, or antibiotics are probably not necessary when the endoscopic closure is confidently performed. This work led to proposal of a local management charter.

17.
Emerg Microbes Infect ; 11(1): 2423-2432, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36098494

RESUMEN

Omicron variant is circulating in the presence of a globally acquired immunity unlike the ancestral SARS-CoV-2 isolate. Herein, we investigated the normalized viral load dynamics and viral culture status in 44 fully vaccinated healthcare workers (HCWs) infected with the Omicron BA.1 variant. Viral load dynamics of 38 unvaccinated HCWs infected with the 20A variant during the first pandemic wave was also studied. We then explored the impact of Omicron infection on pre-existing immunity assessing anti-RBD IgG levels, neutralizing antibody titres against 19A, Delta and Omicron isolates, as well as IFN-γ release following cell stimulation with SARS-CoV-2 peptides. We reported that two weeks after diagnosis a greater proportion of HCWs infected with 20A (78.9%, 15/19) than with Omicron BA.1 (44.7%, 17/38; p = 0.02) were still positive by RT-qPCR. We found that Omicron breakthrough infections led to an overall enhancement of vaccine-induced humoral and cellular immunity as soon as a median [interquartile range] of 8 [7-9] days post symptom onset. Among samples with similar high viral loads, non-culturable samples exhibited higher neutralizing antibody titres and anti-RBD IgG levels than culturable samples. Additionally, Omicron infection led to an enhancement of antibodies neutralization capacity against other SARS-CoV-2 isolates. Taken together, the results suggest that Omicron BA.1 vaccine breakthrough infection is associated with a faster viral clearance than that of the ancestral SARS-CoV-2, in addition this new variant leads to a rapid enhancement of the humoral response against multiple SARS-CoV-2 variants, and of the cellular response.


Asunto(s)
COVID-19 , Vacunas Virales , Humanos , SARS-CoV-2/genética , Esparcimiento de Virus , Anticuerpos Antivirales , Inmunoglobulina G , Anticuerpos Neutralizantes
18.
J Hepatol ; 54(3): 489-96, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21056493

RESUMEN

BACKGROUND & AIMS: Nodular regenerative hyperplasia (NRH) leading to non-cirrhotic portal hypertension has been described in HIV-infected patients and has been linked to didanosine. The relation between NRH and other antiretrovirals remains unclear. METHODS: A case-control study was performed in 13 patients with NRH and 78 controls matched for time of inclusion, baseline CD4, and duration of follow-up. Univariate and multivariate conditional logistic regression analyses were performed. RESULTS: Control patients and patients with NRH were similar at baseline regarding demographics and biological data with the exception of older age for patients with NRH (43.9 vs. 33.5 years, p=0.044). At the time of NRH diagnosis, cases had a lower CD4 count (327 vs. 468/mm(3), p=0.013), a similar CD4 percentage (24 vs. 26.2%, p=0.7), a lower platelet count (169 vs. 228 giga/L, p=0.003) and a higher AST level (33 vs. 26 IU/L, p=0.001) than controls. Univariate analysis demonstrated that patients with NRH had been exposed longer than controls to didanosine, stavudine, tenofovir, didanosine+stavudine, and didanosine+tenofovir. The age at baseline [OR 2.2 (1.0-5.0) per 10 years, p=0.053] and didanosine+stavudine cumulative exposure [OR 3.7 (1.4-10.2) per year, p=0.011] were independently associated with NRH. The age at baseline [OR 2.3 (1.0-5.3) per 10 years, p=0.045], cumulative exposure to didanosine [OR 1.4 (1.1-1.9) per year, p=0.023] and to tenofovir [OR 1.7 (1.0-2.8) per year, p=0.04] were independently associated with NRH when didanosine+stavudine exposure was excluded from the model. CONCLUSIONS: NRH in HIV-infected patients seems strongly related to age and the cumulative exposure to didanosine+stavudine, didanosine, and stavudine.


Asunto(s)
Fármacos Anti-VIH/efectos adversos , Didanosina/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/patología , Hígado/patología , Estavudina/efectos adversos , Adenina/efectos adversos , Adenina/análogos & derivados , Adulto , Terapia Antirretroviral Altamente Activa/efectos adversos , Estudios de Casos y Controles , Femenino , Infecciones por VIH/complicaciones , Humanos , Hiperplasia , Hipertensión Portal/etiología , Hígado/efectos de los fármacos , Regeneración Hepática/efectos de los fármacos , Masculino , Persona de Mediana Edad , Organofosfonatos/efectos adversos , Inhibidores de la Transcriptasa Inversa/efectos adversos , Tenofovir
19.
Eur J Ophthalmol ; 30(5): 874-885, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31238716

RESUMEN

BACKGROUND: Clinical presentation of Lyme-associated uveitis is poorly described. We reported here a case series of seven patients with uveitis related to Lyme disease and a review of the literature. METHODS: A retrospective study in our university hospital between 1 May 2003 and 31 July 2016 on 1006 uveitis patients and review of Pubmed library. RESULTS: Seven patients (71.4% male, mean age = 53 (38-70)) were diagnosed with a Lyme-associated uveitis. All anatomical types of uveitis were found (four intermediate, three anterior, and three posterior uveitis); most were unilateral (n = 6; 85.7%), one granulomatous and two with synechiae. Peripheral retinal vasculitis was present in four patients. They all had a risk of exposure or extra-ophthalmological symptoms. Antibiotic and steroid treatment was rapidly effective in all patients. Four patients presented recurrences of uveitis, of whom two received a second antibiotic treatment, which is quite common in literature. Persistent or recurrence of symptoms can be explained by three hypotheses: (1) reinfection, (2) relapse of original infection, and (3) autoimmune reaction. CONCLUSION: Lyme-associated uveitis appears varied. Hyalitis and involvement of the posterior segment and retinal vasculitis seem to be rather frequent. Its prognosis is mainly good, even if inflammation can be resistant or recurring.


Asunto(s)
Infecciones Bacterianas del Ojo/etiología , Enfermedad de Lyme/complicaciones , Uveítis/etiología , Adulto , Anciano , Antibacterianos/uso terapéutico , Endoftalmitis/diagnóstico , Endoftalmitis/tratamiento farmacológico , Endoftalmitis/etiología , Infecciones Bacterianas del Ojo/diagnóstico , Infecciones Bacterianas del Ojo/tratamiento farmacológico , Femenino , Glucocorticoides/uso terapéutico , Humanos , Enfermedad de Lyme/diagnóstico , Enfermedad de Lyme/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Recurrencia , Vasculitis Retiniana/diagnóstico , Vasculitis Retiniana/tratamiento farmacológico , Vasculitis Retiniana/etiología , Estudios Retrospectivos , Uveítis/diagnóstico , Uveítis/tratamiento farmacológico
20.
BMJ Open ; 10(11): e041268, 2020 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-33234651

RESUMEN

INTRODUCTION: The COVID-19 pandemic caused by SARS-CoV-2 threatens global public health, and there is an urgent public health need to assess acquired immunity to SARS-CoV-2. Serological tests might provide results that can be complementary to or confirm suspected COVID-19 cases and reveal previous infection. The performance of serological assays (sensitivity and specificity) has to be evaluated before their use in the general population. The neutralisation capacity of the produced antibodies also has to be evaluated. METHODS AND ANALYSIS: We set up a prospective, multicentric clinical study to evaluate the performance of serological kits among a population of healthcare workers presenting mild symptoms suggestive of SARS-CoV-2 infection. Four hundred symptomatic healthcare workers will be included in the COVID-SER study. The values obtained from a control cohort included during the prepandemic time will be used as reference. A workflow was set up to study serological response to SARS-CoV-2 infection and to evaluate antibody neutralisation capacity in patients with a confirmed SARS-CoV-2 infection. The sensitivity and specificity of the tests will be assessed using molecular detection of the virus as a reference. The measurement of IgM and IgG antibodies will be performed once per week for 6 consecutive weeks and then at 6, 12, 18, 24 and 36 months after the diagnosis. The kinetics of IgM and IgG will determine the optimal period to perform serological testing. The proportion of false negative PCR tests in symptomatic subjects will be determined on the basis of subsequent seroconversions. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the national review board for biomedical research in April 2020 (Comité de Protection des Personnes Sud Méditerranée I, Marseille, France) (ID RCB 2020-A00932-37). Results will be disseminated through presentations at scientific meetings and publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04341142.


Asunto(s)
Anticuerpos Antivirales/análisis , COVID-19/diagnóstico , Tamizaje Masivo/métodos , Pandemias , SARS-CoV-2/inmunología , COVID-19/epidemiología , Femenino , Humanos , Masculino , Estudios Prospectivos , Pruebas Serológicas
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