Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 55
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Cell ; 184(12): 3205-3221.e24, 2021 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-34015271

RESUMEN

Monoclonal antibodies (mAbs) are a focus in vaccine and therapeutic design to counteract severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants. Here, we combined B cell sorting with single-cell VDJ and RNA sequencing (RNA-seq) and mAb structures to characterize B cell responses against SARS-CoV-2. We show that the SARS-CoV-2-specific B cell repertoire consists of transcriptionally distinct B cell populations with cells producing potently neutralizing antibodies (nAbs) localized in two clusters that resemble memory and activated B cells. Cryo-electron microscopy structures of selected nAbs from these two clusters complexed with SARS-CoV-2 spike trimers show recognition of various receptor-binding domain (RBD) epitopes. One of these mAbs, BG10-19, locks the spike trimer in a closed conformation to potently neutralize SARS-CoV-2, the recently arising mutants B.1.1.7 and B.1.351, and SARS-CoV and cross-reacts with heterologous RBDs. Together, our results characterize transcriptional differences among SARS-CoV-2-specific B cells and uncover cross-neutralizing Ab targets that will inform immunogen and therapeutic design against coronaviruses.


Asunto(s)
Anticuerpos Neutralizantes/inmunología , Linfocitos B/metabolismo , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/química , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/química , Anticuerpos Antivirales/inmunología , Complejo Antígeno-Anticuerpo/química , Complejo Antígeno-Anticuerpo/metabolismo , Reacciones Antígeno-Anticuerpo , Linfocitos B/citología , Linfocitos B/virología , COVID-19/patología , COVID-19/virología , Microscopía por Crioelectrón , Cristalografía por Rayos X , Perfilación de la Expresión Génica , Humanos , Inmunoglobulina A/inmunología , Región Variable de Inmunoglobulina/química , Región Variable de Inmunoglobulina/genética , Dominios Proteicos/inmunología , Multimerización de Proteína , Estructura Cuaternaria de Proteína , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/metabolismo , Análisis de Secuencia de ARN , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/metabolismo
2.
Clin Infect Dis ; 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38466039

RESUMEN

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I2) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multi-societal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multi-focal or diffuse heterogenous intense 18F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more.

3.
J Nucl Cardiol ; 34: 101786, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38472038

RESUMEN

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I2) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multi-societal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multi-focal or diffuse heterogenous intense 18F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more.


Asunto(s)
Infecciones Cardiovasculares , Endocarditis , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fluorodesoxiglucosa F18 , Consenso , Tomografía Computarizada por Rayos X , Imagen Multimodal , Endocarditis/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único
4.
Transpl Infect Dis ; : e14305, 2024 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-38881210

RESUMEN

BACKGROUND: Better access to direct-acting antiviral (DAA) therapy has broadened the utilization of hepatitis C virus (HCV) nucleic acid testing (NAT) positive organs with excellent outcomes. However, DAA therapy has been associated with hepatitis B virus (HBV) reactivation. AIM: To determine the risk of HBV transmission or reactivation with utilization of HBV core antibody positive (HBcAb+) and HCV NAT positive (HCV+) organs, which presumably required DAA therapy. METHODS: The number of HBcAb+ donors with delineated HCV NAT status was obtained from the Organ Procurement and Transplantation Network (OPTN) database. The number of unexpected HBV infections from transplanted organs adjudicated as "proven" or "probable" transmission was obtained from the OPTN Ad Hoc Disease Transmission Advisory Committee database. A chart review of the donors of "proven" or "probable" cases was conducted. RESULTS: From January 1, 2016, to December 31, 2021, 7735 organs were procured from 3767 HBcAb+ donors and transplanted into 7469 recipients; 545 (14.5%) donors were also HCV+. HBV transmission or reactivation occurred in seven recipients. The rate is not significantly different between recipients of HCV+ (0.18%, 2/1115) and the HCV NAT negative (HCV-) organs (0.08%, 5/6354) (p = 0.28) or between recipients of HCV+ and HCV- livers as well as non-liver organs. HBV transmission or reactivation occurred within a median of 319 (range, 41-1117) days post-transplant in the setting of missing, inadequate, or truncated prophylaxis. CONCLUSION: HBV reactivation associated with DAA therapy for HBcAb+ HCV+ organs is less frequent than reported in the non-transplant population, possibly due to the common use of HBV prophylaxis in the at-risk transplant population.

5.
Ann Intern Med ; 176(1): 77-84, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36508742

RESUMEN

BACKGROUND: In the EPIC-HR (Evaluation of Protease Inhibition for Covid-19 in High-Risk Patients) trial, nirmatrelvir plus ritonavir led to an 89% reduction in hospitalization or death among unvaccinated outpatients with early COVID-19. The clinical impact of nirmatrelvir plus ritonavir among vaccinated populations is uncertain. OBJECTIVE: To assess whether nirmatrelvir plus ritonavir reduces risk for hospitalization or death among outpatients with early COVID-19 in the setting of prevalent SARS-CoV-2 immunity and immune-evasive SARS-CoV-2 lineages. DESIGN: Population-based cohort study analyzed to emulate a clinical trial using inverse probability-weighted models to account for anticipated bias in treatment. SETTING: A large health care system providing care for 1.5 million patients in Massachusetts and New Hampshire during the Omicron wave (1 January to 17 July 2022). PATIENTS: 44 551 nonhospitalized adults (90.3% with ≥3 vaccine doses) aged 50 years or older with COVID-19 and no contraindications for nirmatrelvir plus ritonavir. MEASUREMENTS: The primary outcome was a composite of hospitalization within 14 days or death within 28 days of a COVID-19 diagnosis. RESULTS: During the study period, 12 541 (28.1%) patients were prescribed nirmatrelvir plus ritonavir, and 32 010 (71.9%) were not. Patients prescribed nirmatrelvir plus ritonavir were more likely to be older, have more comorbidities, and be vaccinated. The composite outcome of hospitalization or death occurred in 69 (0.55%) patients who were prescribed nirmatrelvir plus ritonavir and 310 (0.97%) who were not (adjusted risk ratio, 0.56 [95% CI, 0.42 to 0.75]). Recipients of nirmatrelvir plus ritonavir had lower risk for hospitalization (adjusted risk ratio, 0.60 [CI, 0.44 to 0.81]) and death (adjusted risk ratio, 0.29 [CI, 0.12 to 0.71]). LIMITATION: Potential residual confounding due to differential access to COVID-19 vaccines, diagnostic tests, and treatment. CONCLUSION: The overall risk for hospitalization or death was already low (1%) after an outpatient diagnosis of COVID-19, but nirmatrelvir plus ritonavir reduced this risk further. PRIMARY FUNDING SOURCE: National Institutes of Health.


Asunto(s)
COVID-19 , Adulto , Humanos , Antivirales , Estudios de Cohortes , COVID-19/epidemiología , Tratamiento Farmacológico de COVID-19 , Prueba de COVID-19 , Vacunas contra la COVID-19 , Ritonavir/uso terapéutico , SARS-CoV-2
6.
N Engl J Med ; 383(24): 2333-2344, 2020 12 10.
Artículo en Inglés | MEDLINE | ID: mdl-33085857

RESUMEN

BACKGROUND: The efficacy of interleukin-6 receptor blockade in hospitalized patients with coronavirus disease 2019 (Covid-19) who are not receiving mechanical ventilation is unclear. METHODS: We performed a randomized, double-blind, placebo-controlled trial involving patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hyperinflammatory states, and at least two of the following signs: fever (body temperature >38°C), pulmonary infiltrates, or the need for supplemental oxygen in order to maintain an oxygen saturation greater than 92%. Patients were randomly assigned in a 2:1 ratio to receive standard care plus a single dose of either tocilizumab (8 mg per kilogram of body weight) or placebo. The primary outcome was intubation or death, assessed in a time-to-event analysis. The secondary efficacy outcomes were clinical worsening and discontinuation of supplemental oxygen among patients who had been receiving it at baseline, both assessed in time-to-event analyses. RESULTS: We enrolled 243 patients; 141 (58%) were men, and 102 (42%) were women. The median age was 59.8 years (range, 21.7 to 85.4), and 45% of the patients were Hispanic or Latino. The hazard ratio for intubation or death in the tocilizumab group as compared with the placebo group was 0.83 (95% confidence interval [CI], 0.38 to 1.81; P = 0.64), and the hazard ratio for disease worsening was 1.11 (95% CI, 0.59 to 2.10; P = 0.73). At 14 days, 18.0% of the patients in the tocilizumab group and 14.9% of the patients in the placebo group had had worsening of disease. The median time to discontinuation of supplemental oxygen was 5.0 days (95% CI, 3.8 to 7.6) in the tocilizumab group and 4.9 days (95% CI, 3.8 to 7.8) in the placebo group (P = 0.69). At 14 days, 24.6% of the patients in the tocilizumab group and 21.2% of the patients in the placebo group were still receiving supplemental oxygen. Patients who received tocilizumab had fewer serious infections than patients who received placebo. CONCLUSIONS: Tocilizumab was not effective for preventing intubation or death in moderately ill hospitalized patients with Covid-19. Some benefit or harm cannot be ruled out, however, because the confidence intervals for efficacy comparisons were wide. (Funded by Genentech; ClinicalTrials.gov number, NCT04356937.).


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Receptores de Interleucina-6/antagonistas & inhibidores , Adulto , Anciano , Anciano de 80 o más Años , Boston , COVID-19/mortalidad , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Humanos , Intubación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Terapia Respiratoria , Insuficiencia del Tratamiento , Adulto Joven
7.
Transpl Infect Dis ; 25(1): e14013, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36694448

RESUMEN

BACKGROUND: Decisions to transplant organs from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test-positive (NAT+) donors must balance risk of donor-derived transmission events (DDTE) with the scarcity of available organs. METHODS: Organ Procurement and Transplantation Network (OPTN) data were used to compare organ utilization and recipient outcomes between SARS-CoV-2 NAT+ and NAT- donors. NAT+ was defined by either a positive upper or lower respiratory tract (LRT) sample within 21 days of procurement. Potential DDTE were adjudicated by OPTN Disease Transmission Advisory Committee. RESULTS: From May 27, 2021 (date of OTPN policy for required LRT testing of lung donors) to January 31, 2022, organs were recovered from 617 NAT+ donors from all OPTN regions and 53 of 57 (93%) organ procurement organizations. NAT+ donors were younger and had higher organ quality scores for kidney and liver. Organ utilization was lower for NAT+ donors compared to NAT- donors. A total of 1241 organs (776 kidneys, 316 livers, 106 hearts, 22 lungs, and 21 other) were transplanted from 514 NAT+ donors compared to 21 946 organs from 8853 NAT- donors. Medical urgency was lower for recipients of NAT+ liver and heart transplants. The median waitlist time was longer for liver recipients of NAT+ donors. The match run sequence number for final acceptor was higher for NAT+ donors for all organ types. Outcomes for hospital length of stay, 30-day mortality, and 30-day graft loss were similar for all organ types. No SARS-CoV-2 DDTE occurred in this interval. CONCLUSIONS: Transplantation of SARS-CoV-2 NAT+ donor organs appears safe for short-term outcomes of death and graft loss and ameliorates the organ shortage. Further study is required to assure comparable longer term outcomes.


Asunto(s)
COVID-19 , Ácidos Nucleicos , Trasplante de Órganos , Obtención de Tejidos y Órganos , Humanos , SARS-CoV-2 , Comités Consultivos , Donantes de Tejidos
8.
Anesth Analg ; 136(1): 70-78, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36219579

RESUMEN

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) can present with severe respiratory distress requiring intensive care unit (ICU)-level care. Such care often requires placement of an arterial line for monitoring of pulmonary disease progression, hemodynamics, and laboratory tests. During the first wave of the COVID-19 pandemic in March 2020, experienced physicians anecdotally reported multiple attempts, decreased insertion durations, and greater need for replacement of arterial lines in patients with COVID-19 due to persistent thrombosis. Because invasive procedures in patients with COVID-19 may increase the risk for caregiver infection, better defining difficulties in maintaining arterial lines in COVID-19 patients is important. We sought to explore the association between COVID-19 infection and arterial line thrombosis in critically ill patients. METHODS: In this primary exploratory analysis, a multivariable Fine-Gray subdistribution hazard model was used to retrospectively estimate the association between critically ill COVID-19 (versus sepsis/acute respiratory distress syndrome [ARDS]) patients and the risk of arterial line removal for thrombosis (with arterial line removal for any other reason treated as a competing risk). As a sensitivity analysis, we compared the number of arterial line clots per 1000 arterial line days between critically ill COVID-19 and sepsis/ARDS patients using multivariable negative binomial regression. RESULTS: We retrospectively identified 119 patients and 200 arterial line insertions in patients with COVID-19 and 54 patients and 68 arterial line insertions with non-COVID ARDS. Using a Fine-Gray subdistribution hazard model, we found the adjusted subdistribution hazard ratio (95% confidence interval [CI]) for arterial line clot to be 2.18 (1.06-4.46) for arterial lines placed in COVID-19 patients versus non-COVID-19 sepsis/ARDS patients ( P = .034). Patients with COVID-19 had 36.3 arterial line clots per 1000 arterial line days compared to 19.1 arterial line clots per 1000 arterial line days in patients without COVID-19 (adjusted incidence rate ratio [IRR] [95% CI], 1.78 [0.94-3.39]; P = .078). CONCLUSIONS: Our study suggests that arterial line complications due to thrombosis are more likely in COVID-19 patients and supports the need for further research on the association between COVID-19 and arterial line dysfunction requiring replacement.


Asunto(s)
COVID-19 , Síndrome de Dificultad Respiratoria , Sepsis , Trombosis , Humanos , COVID-19/epidemiología , Estudios Retrospectivos , Pandemias , Enfermedad Crítica/epidemiología , Unidades de Cuidados Intensivos , Síndrome de Dificultad Respiratoria/epidemiología
9.
Curr Cardiol Rep ; 25(12): 1873-1881, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38117447

RESUMEN

PURPOSE OF REVIEW: The question of antibiotic prophylaxis and its role in prevention of infective endocarditis (IE) remains controversial, with differing recommendations from international societies. The aim of this review was to compare and contrast current recommendations on antibiotic prophylaxis for IE by the American Heart Association (AHA), the European Society of Cardiology (ESC), and the National Institute for Health and Care Excellence (NICE) and highlight the evidence supporting these recommendations. RECENT FINDINGS: International guidelines for administration of antibiotic prophylaxis for prevention of IE are largely unchanged since 2009. Studies on the impact of the more restrictive antibiotic prophylaxis recommendations are conflicting, with several studies suggesting lack of adherence to current guidance from the ESC (2015), NICE (2016), and AHA (2021). The question of antibiotic prophylaxis in patients with IE remains controversial, with differing recommendations from international societies. Despite the change in guidelines more than 15 years ago, lack of adherence to current guidelines persists. Due to the lack of high-quality evidence and the conflicting results from observational studies along with the lack of randomized clinical trials, the question of whether to recommend antibiotic prophylaxis or not in certain patient populations remains unanswered and remains largely based on expert consensus opinion.


Asunto(s)
Cardiología , Endocarditis Bacteriana , Endocarditis , Estados Unidos , Humanos , Antibacterianos/uso terapéutico , Endocarditis Bacteriana/prevención & control , Endocarditis Bacteriana/tratamiento farmacológico , Endocarditis/prevención & control , Profilaxis Antibiótica
10.
Clin Infect Dis ; 75(9): 1610-1617, 2022 10 29.
Artículo en Inglés | MEDLINE | ID: mdl-35271726

RESUMEN

BACKGROUND: Burkholderia cepacia complex is a group of potential nosocomial pathogens often linked to contaminated water. We report on a cluster of 8 B. cepacia complex infections in cardiothoracic intensive care unit patients, which were attributed to contaminated extracorporeal membrane oxygenation (ECMO) water heaters. METHODS: In December 2020, we identified an increase in B. cepacia complex infections in the cardiothoracic intensive care unit at Brigham and Women's Hospital. We sought commonalities, sequenced isolates, obtained environmental specimens, and enacted mitigation measures. RESULTS: Whole-genome sequencing of 13 B. cepacia complex clinical specimens between November 2020 and February 2021 identified 6 clonally related isolates, speciated as Burkholderia contaminans. All 6 occurred in patients on ECMO. Microbiology review identified 2 additional B. contaminans cases from June 2020 that may have also been cluster related, including 1 in a patient receiving ECMO. All 8 definite or probable cluster cases required treatment; 3 patients died, and 3 experienced recurrent infections. After ECMO was identified as the major commonality, all 9 of the hospital's ECMO water heaters were cultured, and B. contaminans grew in all cultures. Cultures from air sampled adjacent to the water heaters were negative. Water heater touch screens were culture positive for B. contaminans, and the sink drain in the ECMO heater reprocessing room also grew clonal B. contaminans. Observations of reprocessing revealed opportunities for cross-contamination between devices through splashing from the contaminated sink. The cluster was aborted by removing all water heaters from clinical service. CONCLUSIONS: We identified a cluster of 8 B. cepacia complex infections associated with contaminated ECMO water heaters. This cluster underscores the potential risks associated with water-based ECMO heaters and, more broadly, water-based care for vulnerable patients.


Asunto(s)
Infecciones por Burkholderia , Complejo Burkholderia cepacia , Burkholderia cepacia , Infección Hospitalaria , Oxigenación por Membrana Extracorpórea , Humanos , Femenino , Oxigenación por Membrana Extracorpórea/efectos adversos , Agua , Infecciones por Burkholderia/epidemiología , Infecciones por Burkholderia/microbiología , Contaminación de Medicamentos , Infección Hospitalaria/microbiología , Brotes de Enfermedades
11.
Clin Infect Dis ; 74(7): 1275-1278, 2022 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-34363462

RESUMEN

The impact of coronavirus disease 2019 vaccination on viral characteristics of breakthrough infections is unknown. In this prospective cohort study, incidence of severe acute respiratory syndrome coronavirus 2 infection decreased following vaccination. Although asymptomatic positive tests were observed following vaccination, the higher cycle thresholds, repeat negative tests, and inability to culture virus raise questions about their clinical significance.


Asunto(s)
COVID-19 , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19 , Personal de Salud , Humanos , Incidencia , Estudios Prospectivos , SARS-CoV-2 , Vacunación
12.
N Engl J Med ; 380(17): 1606-1617, 2019 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-30946553

RESUMEN

BACKGROUND: Hearts and lungs from donors with hepatitis C viremia are typically not transplanted. The advent of direct-acting antiviral agents to treat hepatitis C virus (HCV) infection has raised the possibility of substantially increasing the donor organ pool by enabling the transplantation of hearts and lungs from HCV-infected donors into recipients who do not have HCV infection. METHODS: We conducted a trial involving transplantation of hearts and lungs from donors who had hepatitis C viremia, irrespective of HCV genotype, to adults without HCV infection. Sofosbuvir-velpatasvir, a pangenotypic direct-acting antiviral regimen, was preemptively administered to the organ recipients for 4 weeks, beginning within a few hours after transplantation, to block viral replication. The primary outcome was a composite of a sustained virologic response at 12 weeks after completion of antiviral therapy for HCV infection and graft survival at 6 months after transplantation. RESULTS: A total of 44 patients were enrolled: 36 received lung transplants and 8 received heart transplants. The median viral load in the HCV-infected donors was 890,000 IU per milliliter (interquartile range, 276,000 to 4.63 million). The HCV genotypes were genotype 1 (in 61% of the donors), genotype 2 (in 17%), genotype 3 (in 17%), and indeterminate (in 5%). A total of 42 of 44 recipients (95%) had a detectable hepatitis C viral load immediately after transplantation, with a median of 1800 IU per milliliter (interquartile range, 800 to 6180). Of the first 35 patients enrolled who had completed 6 months of follow-up, all 35 patients (100%; exact 95% confidence interval, 90 to 100) were alive and had excellent graft function and an undetectable hepatitis C viral load at 6 months after transplantation; the viral load became undetectable by approximately 2 weeks after transplantation, and it subsequently remained undetectable in all patients. No treatment-related serious adverse events were identified. More cases of acute cellular rejection for which treatment was indicated occurred in the HCV-infected lung-transplant recipients than in a cohort of patients who received lung transplants from donors who did not have HCV infection. This difference was not significant after adjustment for possible confounders. CONCLUSIONS: In patients without HCV infection who received a heart or lung transplant from donors with hepatitis C viremia, treatment with an antiviral regimen for 4 weeks, initiated within a few hours after transplantation, prevented the establishment of HCV infection. (Funded by the Mendez National Institute of Transplantation Foundation and others; DONATE HCV ClinicalTrials.gov number, NCT03086044.).


Asunto(s)
Antivirales/uso terapéutico , Carbamatos/uso terapéutico , Trasplante de Corazón , Hepacivirus/aislamiento & purificación , Hepatitis C/transmisión , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Trasplante de Pulmón , Sofosbuvir/uso terapéutico , Adulto , Factores de Edad , Anciano , Femenino , Rechazo de Injerto , Supervivencia de Injerto , Hepacivirus/inmunología , Hepatitis C/prevención & control , Anticuerpos contra la Hepatitis C/sangre , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , ARN Viral/sangre , Donantes de Tejidos
13.
Angew Chem Int Ed Engl ; 60(49): 25966-25972, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-34534408

RESUMEN

Coronavirus disease 2019 (COVID-19) manifests with high clinical variability and warrants sensitive and specific assays to analyze immune responses in infected and vaccinated individuals. Using Single Molecule Arrays (Simoa), we developed an assay to assess antibody neutralization with high sensitivity and multiplexing capabilities based on antibody-mediated blockage of the ACE2-spike interaction. The assay does not require live viruses or cells and can be performed in a biosafety level 2 laboratory within two hours. We used this assay to assess neutralization and antibody levels in patients who died of COVID-19 and patients hospitalized for a short period of time and show that neutralization and antibody levels increase over time. We also adapted the assay for SARS-CoV-2 variants and measured neutralization capacity in pre-pandemic healthy, COVID-19 infected, and vaccinated individuals. This assay is highly adaptable for clinical applications, such as vaccine development and epidemiological studies.


Asunto(s)
Anticuerpos Neutralizantes/inmunología , COVID-19/inmunología , Pruebas de Neutralización/métodos , SARS-CoV-2/inmunología , Enzima Convertidora de Angiotensina 2/inmunología , Enzima Convertidora de Angiotensina 2/metabolismo , Anticuerpos Antivirales/inmunología , Reacciones Antígeno-Anticuerpo , COVID-19/patología , COVID-19/virología , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/inmunología , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Humanos , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/metabolismo , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/metabolismo
14.
N Engl J Med ; 376(10): 939-946, 2017 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-28273010

RESUMEN

Background Babesiosis, a tickborne zoonotic disease caused by intraerythrocytic protozoa of the genus babesia, is characterized by nonimmune hemolytic anemia that resolves with antimicrobial treatment and clearance of parasitemia. The development of warm-antibody autoimmune hemolytic anemia (also known as warm autoimmune hemolytic anemia [WAHA]) in patients with babesiosis has not previously been well described. Methods After the observation of sporadic cases of WAHA that occurred after treatment of patients for babesiosis, we conducted a retrospective cohort study of all the patients with babesiosis who were cared for at our center from January 2009 through June 2016. Data on covariates of interest were extracted from the medical records, including any hematologic complications that occurred within 3 months after the diagnosis and treatment of babesiosis. Results A total of 86 patients received a diagnosis of babesiosis during the 7.5-year study period; 18 of these patients were asplenic. WAHA developed in 6 patients 2 to 4 weeks after the diagnosis of babesiosis, by which time all the patients had had clinical and laboratory responses to antimicrobial treatment of babesiosis, including clearance of Babesia microti parasitemia. All 6 patients were asplenic (P<0.001) and had positive direct antiglobulin tests for IgG and complement component 3; warm autoantibodies were identified in all these patients. No alternative explanation for clinical hemolysis was found. WAHA required immunosuppressive treatment in 4 of the 6 patients. Conclusions We documented post-babesiosis WAHA in patients who did not have a history of autoimmunity; asplenic patients appeared to be particularly at risk.


Asunto(s)
Anemia Hemolítica Autoinmune/parasitología , Babesia microti , Babesiosis/complicaciones , Esplenectomía/efectos adversos , Adulto , Anemia Hemolítica Autoinmune/inmunología , Autoanticuerpos/sangre , Babesia microti/inmunología , Babesia microti/aislamiento & purificación , Babesiosis/tratamiento farmacológico , Femenino , Humanos , Masculino , Factores de Riesgo , Reacción a la Transfusión
18.
Clin Infect Dis ; 65(3): 510-513, 2017 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-28419210

RESUMEN

Viral infections have been reported with dasatinib use, but its cytomegalovirus risk after hematopoietic-cell transplantation (HCT) is not known. We found that post-HCT dasatinib use increased the risk of cytomegalovirus reactivation (adjusted hazard ratio, 7.65; 95% confidence interval, 1.84-31.7), controlling for acute graft-versus-host disease, in 109 patients with Philadelphia-chromosome-positive malignancies.


Asunto(s)
Antineoplásicos/efectos adversos , Infecciones por Citomegalovirus/epidemiología , Citomegalovirus , Dasatinib/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adulto , Anciano , Antineoplásicos/uso terapéutico , Estudios de Cohortes , Infecciones por Citomegalovirus/inducido químicamente , Dasatinib/uso terapéutico , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/epidemiología , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto Joven
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA