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1.
JMIR Public Health Surveill ; 10: e53580, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39226091

RESUMEN

BACKGROUND: Following the initial acute phase of COVID-19, health care resource use has escalated among individuals with SARS-CoV-2 infection. OBJECTIVE: This study aimed to compare new diagnoses of long COVID and the demand for health services in the general population after the Omicron wave with those observed during the pre-Omicron waves, using similar assessment protocols for both periods and to analyze the influence of vaccination. METHODS: This matched retrospective case-control study included patients of both sexes diagnosed with acute SARS-CoV-2 infection using reverse transcription polymerase chain reaction or antigen tests in the hospital microbiology laboratory during the pandemic period regardless of whether the patients were hospitalized. We included patients of all ages from 2 health care departments that cover 604,000 subjects. The population was stratified into 2 groups, youths (<18 years) and adults (≥18 years). Patients were followed-up for 6 months after SARS-CoV-2 infection. Previous vaccination, new diagnoses, and the use of health care resources were recorded. Patients were compared with controls selected using a prospective score matched for age, sex, and the Charlson index. RESULTS: A total of 41,577 patients with a history of prior COVID-19 infection were included, alongside an equivalent number of controls. This cohort encompassed 33,249 (80%) adults aged ≥18 years and 8328 (20%) youths aged <18 years. Our analysis identified 40 new diagnoses during the observation period. The incidence rate per 100 patients over a 6-month period was 27.2 for vaccinated and 25.1 for unvaccinated adults (P=.09), while among youths, the corresponding rates were 25.7 for vaccinated and 36.7 for unvaccinated individuals (P<.001). Overall, the incidence of new diagnoses was notably higher in patients compared to matched controls. Additionally, vaccinated patients exhibited a reduced incidence of new diagnoses, particularly among women (P<.001) and younger patients (P<.001) irrespective of the number of vaccine doses administered and the duration since the last dose. Furthermore, an increase in the use of health care resources was observed in both adult and youth groups, albeit with lower figures noted in vaccinated individuals. In the comparative analysis between the pre-Omicron and Omicron waves, the incidence of new diagnoses was higher in the former; however, distinct patterns of diagnosis were evident. Specifically, depressed mood (P=.03), anosmia (P=.003), hair loss (P<.001), dyspnea (<0.001), chest pain (P=.04), dysmenorrhea (P<.001), myalgia (P=.011), weakness (P<.001), and tachycardia (P=.015) were more common in the pre-Omicron period. Similarly, health care resource use, encompassing primary care, specialist, and emergency services, was more pronounced in the pre-Omicron wave. CONCLUSIONS: The rise in new diagnoses following SARS-CoV-2 infection warrants attention due to its potential implications for health systems, which may necessitate the allocation of supplementary resources. The absence of vaccination protection presents a challenge to the health care system.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Masculino , Estudios de Casos y Controles , Femenino , Adulto , Adolescente , Estudios Retrospectivos , Persona de Mediana Edad , Niño , Adulto Joven , Anciano , SARS-CoV-2 , Preescolar , Vacunas contra la COVID-19/administración & dosificación , Pandemias , Costo de Enfermedad , Lactante , Síndrome Post Agudo de COVID-19
2.
Mediterr J Hematol Infect Dis ; 16(1): e2024065, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39258183

RESUMEN

Background: Cytomegalovirus (CMV) infection is a common complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and in patients receiving novel hematological therapies. Its impact on morbidity and mortality necessitates effective management strategies. Despite recent advances in diagnostics and treatment, unresolved questions persist regarding monitoring and treatment, prompting the need for updated recommendations. Methods: A consensus was reached among a panel of experts selected for their expertise in CMV research and clinical practice. Key clinical areas and questions were identified based on previous surveys and literature reviews. Recommendations were formulated through consensus and graded using established guidelines. Results: Recommendations were provided for virological monitoring, including the timing and frequency of CMV DNAemia surveillance, especially during letermovir (LMV) prophylaxis. We evaluated the role of CMV DNA load quantification in diagnosing CMV disease, particularly pneumonia and gastrointestinal involvement, along with the utility of specific CMV immune monitoring in identifying at-risk patients. Strategies for tailoring LMV prophylaxis, managing breakthrough DNAemia, and implementing secondary prophylaxis in refractory cases were outlined. Additionally, criteria for initiating early antiviral treatment based on viral load dynamics were discussed. Conclusion: The consensus provides updated recommendations for managing CMV infection in hematological patients, focusing on unresolved issues in monitoring, prophylaxis, treatment, and resistance. These recommendations aim to guide clinical practice and improve outcomes in this high-risk population. Further research is warranted to validate these recommendations and address ongoing challenges in CMV management with emerging antiviral combinations, particularly in pediatric populations.

3.
Transplant Rev (Orlando) ; 38(4): 100875, 2024 08 05.
Artículo en Inglés | MEDLINE | ID: mdl-39168020

RESUMEN

Cytomegalovirus (CMV) infection remains a significant challenge in solid organ transplantation (SOT). The last international consensus guidelines on the management of CMV in SOT were published in 2018, highlighting the need for revision to incorporate recent advances, notably in cell-mediated immunity monitoring, which could alter the current standard of care. A working group including members from the Group for the Study of Infection in Transplantation and the Immunocompromised Host (GESITRA-IC) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Transplantation (SET), developed consensus-based recommendations for managing CMV infection in SOT recipients. Recommendations were classified based on evidence strength and quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The final recommendations were endorsed through a consensus meeting and approved by the expert panel.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39112116

RESUMEN

Pneumonia continues to be one of the most frequent infectious syndromes and a relevant cause of death and health resources utilization. The OPENIN ("Optimización de procesos clínicos para el diagnóstico y tratamiento de infecciones") Group is composed of Infectious Diseases specialists and Microbiologists and aims at generating recommendations that can contribute to improve the approach to processes with high impact on the health system. Such task relies on a critical review of the available scientific evidence. The first Group meeting (held in October 2023) aimed at answering the following questions: Can we optimize the syndromic and microbiological diagnosis of pneumonia? Is it feasible to safely shorten the length of antibiotic therapy? And, is there any role for the immunomodulatory strategies based on the adjuvant use of steroids, macrolides or immunoglobulins? The present review summarizes the literature reviewed for that meeting and offers a series of expert recommendations.

5.
J Med Virol ; 96(7): e29790, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38994662

RESUMEN

The effect of COVID-19 booster vaccination on SARS-CoV-2 T-cell mediated immune responses in elderly nursing home residents has not been explored in depth. Thirty-nine elderly nursing home residents (median age, 91 years) were included, all fully vaccinated with mRNA vaccines. The frequency of and the integrated mean fluorescence (iMFI) for peripheral blood SARS-CoV-2-Spike reactive IFN-γ-producing CD4+ or CD8+ T cells before and after the first (Pre-3D and Post-3D) and second (Pre-4D and Post-4D) vaccine booster doses was determined using flow cytometry for an intracellular staining method. 3D increased significantly (p = 0.01) the percentage of participants displaying detectable SARS-CoV-2-T-cell responses compared with pre-3D (97% vs. 74%). The magnitude of the increase was statistically significant for CD8+ T cells (p = 0.007) but not for CD4+ T cells (p = 0.77). A trend towards higher frequencies of peripheral blood SARS-CoV-2-CD8+ T cells was observed post-3D compared with pre-3D (p = 0.06). The percentage of participants with detectable SARS-S-CoV-2 CD4+ T-cell responses decreased post-4D (p = 0.035). Following 4D, a nonsignificant decrease in the frequencies of both T cell subsets was noticed (p = 0.94 for CD8+ T cells and p = 0.06 for CD4+ T cells). iMFI data mirrored that of T-cell frequencies. The kinetics of SARS-CoV-2 CD8+ and CD4+ T cells following receipt of 3D and 4D were comparable across SARS-CoV-2-experienced and -naïve participants and between individuals receiving a homologous or heterologous vaccine booster. 3D increased the percentage of elderly nursing home residents displaying detectable SARS-CoV-2 T-cell responses but had a marginal effect on T-cell frequencies. The impact of 4D on SARS-CoV-2 T-cell responses was negligible; whether this was due to suboptimal priming or rapid waning could not be ascertained.


Asunto(s)
Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Vacunas contra la COVID-19 , COVID-19 , Inmunización Secundaria , Casas de Salud , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , Anciano de 80 o más Años , Masculino , Glicoproteína de la Espiga del Coronavirus/inmunología , Femenino , Linfocitos T CD8-positivos/inmunología , COVID-19/inmunología , COVID-19/prevención & control , Linfocitos T CD4-Positivos/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , SARS-CoV-2/inmunología , Anciano , Interferón gamma , Vacunas de ARNm
6.
Clin Infect Dis ; 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39041385

RESUMEN

Cytomegalovirus (CMV) infection and disease are important causes of morbidity and mortality in transplant recipients. For the purpose of developing consistent reporting of CMV outcomes in clinical trials, definitions of CMV infection and disease were developed and most recently published in 2017. Since then, there have been major developments, including registration of new antiviral agents. Therefore, the Transplant Associated Virus Infections Forum, which consists of scientists, clinicians, regulators, and industry representatives, has produced an updated version of these definitions that incorporates recent knowledge with the aim of supporting clinical research and drug development. This also includes an update regarding the definition of resistant and refractory CMV infections previously published in 2019. As the field evolves, the need for updates of these definitions is clear, and collaborative efforts among clinicians, scientists, regulators, and industry representatives can provide a platform for this work.

8.
Eur J Clin Microbiol Infect Dis ; 43(9): 1699-1709, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38958810

RESUMEN

PURPOSE: Molecular screening for Mycobacterium tuberculosis (MTB) can lead to rapid empirical treatment inception and reduce hospitalization time and complementary diagnostic tests. However, in low-prevalence settings, the cost-benefit balance remains controversial due to the high cost. METHODS: We used a Markov model to perform an economic analysis to evaluate the profit after implementing molecular MTB screening (Period B) compared with conventional culture testing (Period A) in respiratory samples from 7,452 consecutive subjects with presumed tuberculosis (TB). RESULTS: The proportion of positivity was comparable between both periods (P > 0.05), with a total of 2.16 and 1.78 samples/patient requested in periods A and B, respectively (P < 0.001). The mean length of hospital stay was 8.66 days (95%CI: 7.63-9.70) in Period B and 11.51 days (95%CI: 10.15-12.87) in Period A (P = 0.001). The healthcare costs associated with diagnosing patients with presumed TB were reduced by €717.95 per patient with PCR screening. The probability of remaining hospitalized and the need for a greater number of outpatient specialty care visits were the variables with the most weight in the model. CONCLUSION: Employing PCR as an MTB screening method in a low-prevalence setting may increase the profits to the system.


Asunto(s)
Análisis Costo-Beneficio , Técnicas de Diagnóstico Molecular , Mycobacterium tuberculosis , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Femenino , Masculino , Persona de Mediana Edad , Técnicas de Diagnóstico Molecular/economía , Técnicas de Diagnóstico Molecular/métodos , Adulto , Anciano , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/microbiología , Tuberculosis Pulmonar/economía , Cadenas de Markov , Tuberculosis/diagnóstico , Tuberculosis/microbiología , Tuberculosis/economía , Adulto Joven
9.
Microbiol Spectr ; 12(8): e0391023, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-38916338

RESUMEN

The Platelia Aspergillus Antigen immunoassay is the "gold standard" for Aspergillus galactomannan (GLM) measurement in sera and bronchoalveolar lavage (BAL) for the diagnosis of invasive pulmonary aspergillosis (IPA). We evaluated the performance of the Aspergillus GLM antigen Virclia Monotest compared to the Platelia assay. A total of 535 specimens [320 sera, 86 bronchial aspirates (BAs), 70 BAL, and 59 tracheal aspirates (TAs)] from 177 adult patients (72 hematological, 32 Intensive Care Unit, and 73 hospitalized in other wards) were processed for GLM testing upon clinical request. One patient had proven IPA, and 11 had probable disease. After excluding indeterminate Virclia results (n = 38), 396 specimens yielded concordant results (56 positive and 340 negative) and 101 discordant results (Virclia positive/Platelia negative, n = 95). The overall agreement between immunoassays was higher for sera (κ 0.56) than for BAL (κ ≤ 0.24) or BAS and TA (κ ≤ 0.22). When considering all specimen types in combination, the overall sensitivity and specificity of the Virclia assay for the diagnosis of proven/probable IPA were 100% and 65%, respectively, and for the Platelia immunoassay, sensitivity and specificity were 91.7% and 89.4%, respectively. The correlation between index values by both immunoassays was strong for serum/BAL (ρ = 0.73; P < 0.001) and moderate for BAS/TA (Rho = 0.52; P = 0.001). The conversion of Virclia index values into the Platelia index could be derived by the formula y = (11.97 * X)/3.62 + X). Data from GLM-positive serum/BAL clinical specimens fitted the regression model optimally (R2 = 0.94), whereas that of BAS and TA data did not (R2 = 0.11). Further studies are needed to determine whether the Virclia assay may be an alternative to the Platelia assay for GLM measurement in sera and lower respiratory tract specimens.IMPORTANCEGalactomannan detection in serum or bronchoalveolar fluid specimens is pivotal for the diagnosis of invasive pulmonary aspergillosis (IPA). The Platelia Aspergillus Antigen immunoassay has become the "gold standard" for Aspergillus GLM measurement. Here, we provide data suggesting that the Virclia Monotest assay, which displays several operational advantages compared with the Platelia assay, may become an alternative to the Platelia assay, although further studies are needed to validate this assumption. We also provide a formula allowing the conversion of Virclia index values into Platelia values. The study may contribute toward positioning the Virclia assay within the diagnostic algorithm of IPA.


Asunto(s)
Antígenos Fúngicos , Aspergillus , Galactosa , Mananos , Sensibilidad y Especificidad , Humanos , Galactosa/análogos & derivados , Mananos/análisis , Mananos/sangre , Antígenos Fúngicos/análisis , Antígenos Fúngicos/sangre , Antígenos Fúngicos/inmunología , Aspergillus/inmunología , Aspergillus/aislamiento & purificación , Aspergillus/química , Femenino , Masculino , Inmunoensayo/métodos , Persona de Mediana Edad , Aspergilosis Pulmonar Invasiva/diagnóstico , Adulto , Líquido del Lavado Bronquioalveolar/microbiología , Líquido del Lavado Bronquioalveolar/química , Anciano , Anciano de 80 o más Años
10.
Plant J ; 119(4): 1844-1858, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38900073

RESUMEN

Fruit ripening is an essential developmental stage in Angiosperms triggered by hormonal signals such as ethylene, a major player in climacteric ripening. Melon is a unique crop showing both climacteric and non-climacteric cultivars, offering an ideal model for dissecting the genetic mechanisms underpinning this process. The major quantitative trait locus ETHQV8.1 was previously identified as a key regulator of melon fruit ripening. Here, we narrowed down ETHQV8.1 to a precise genomic region containing a single gene, the transcription factor CmERF024. Functional validation using CRISPR/Cas9 knock-out plants unequivocally identified CmERF024 as the causal gene governing ETHQV8.1. The erf024 mutants exhibited suppression of ethylene production, leading to a significant delay and attenuation of fruit ripening. Integrative multi-omic analyses encompassing RNA-seq, DAP-seq, and DNase-seq revealed the association of CmERF024 with chromatin accessibility and gene expression dynamics throughout fruit ripening. Our data suggest CmERF024 as a novel regulator of climacteric fruit ripening in melon.


Asunto(s)
Cucurbitaceae , Etilenos , Frutas , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Factores de Transcripción , Frutas/genética , Frutas/crecimiento & desarrollo , Frutas/metabolismo , Etilenos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Cucurbitaceae/genética , Cucurbitaceae/crecimiento & desarrollo , Cucurbitaceae/metabolismo , Sitios de Carácter Cuantitativo/genética , Reguladores del Crecimiento de las Plantas/metabolismo , Plantas Modificadas Genéticamente
11.
Angew Chem Int Ed Engl ; 63(34): e202405823, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-38856634

RESUMEN

Invasive fungal disease accounts for about 3.8 million deaths annually, an unacceptable rate that urgently prompts the discovery of new knowledge-driven treatments. We report the use of camelid single-domain nanobodies (Nbs) against fungal ß-1,3-glucanosyltransferases (Gel) involved in ß-1,3-glucan transglycosylation. Crystal structures of two Nbs with Gel4 from Aspergillus fumigatus revealed binding to a dissimilar CBM43 domain and a highly conserved catalytic domain across fungal species, respectively. Anti-Gel4 active site Nb3 showed significant antifungal efficacy in vitro and in vivo prophylactically and therapeutically against different A. fumigatus and Cryptococcus neoformans isolates, reducing the fungal burden and disease severity, thus significantly improving immunocompromised animal survival. Notably, C. deneoformans (serotype D) strains were more susceptible to Nb3 and genetic Gel deletion than C. neoformans (serotype A) strains, indicating a key role for ß-1,3-glucan remodelling in C. deneoformans survival. These findings add new insight about the role of ß-1,3-glucan in fungal biology and demonstrate the potential of nanobodies in targeting fungal enzymes to combat invasive fungal diseases.


Asunto(s)
Aspergillus fumigatus , Dominio Catalítico , Anticuerpos de Dominio Único , Anticuerpos de Dominio Único/química , Anticuerpos de Dominio Único/inmunología , Anticuerpos de Dominio Único/farmacología , Aspergillus fumigatus/inmunología , Aspergillus fumigatus/enzimología , Cryptococcus neoformans/enzimología , Cryptococcus neoformans/inmunología , Antifúngicos/química , Antifúngicos/farmacología , Animales , Ratones , Glucano Endo-1,3-beta-D-Glucosidasa
13.
Microbiol Spectr ; 12(7): e0420123, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38842363

RESUMEN

Quantitation of cytomegalovirus (CMV) DNA load in specimens other than blood such as bronchoalveolar lavages, intestinal biopsies, or urine has become a common practice as an ancillary tool for the diagnosis of CMV pneumonitis, intestinal disease, or congenital infection, respectively. Nevertheless, most commercially available CMV PCR platforms have not been validated for CMV DNA detection in these specimen types. In this study, a laboratory-developed test based on Alinity m CMV ("Alinity LDT") was evaluated. Reproducibility assessment using spiked bronchial aspirate (BAS) or urine samples showed low standard deviations of 0.08 and 0.27 Log IU/mL, respectively. Evaluating the clinical performance of Alinity LDT in comparison to a laboratory-developed test based on RealTime CMV ("RealTime LDT") showed good concordance across 200 clinical specimens including respiratory specimens, intestinal biopsies, urine, and stool. A high Pearson's correlation coefficient of r = 0.92, a low mean bias of -0.12 Log IU/mL, a good qualitative agreement of 90%, and a Cohen's kappa value of 0.76 (substantial agreement) were observed. In separate analyses of the sample types BAS, tracheal aspirates, bronchoalveolar lavage, biopsies, and urine, the assay results correlated well between the two platforms with r values between 0.88 and 0.99 and a bias <0.5 Log IU/mL. Overall, the fully automated, continuous, random access Alinity LDT yielded good reproducibility, high concordance, and good correlation to RealTime LDT in respiratory, gastrointestinal, and urine samples and may enhance patient management with rapid result reporting.IMPORTANCEIn transplant recipients, a major cause for morbidity and mortality is end-organ disease by primary or secondary CMV infection of the respiratory or gastrointestinal tract. In addition, sensorineural hearing loss and neurodevelopmental abnormalities are frequent sequelae of congenital CMV infections in newborns. Standard of care for highly sensitive detection and quantitation of the CMV DNA load in plasma and whole blood specimens is real-time PCR testing. Beyond that, there is a need for quantitative determination of CMV DNA levels in respiratory, gastrointestinal, and urinary tract specimens using a highly automated, random access CMV PCR assay with a short turnaround time to enable early diagnosis and treatment. In the present study, clinical performance of the fully automated Alinity m analyzer in comparison to the current RealTime LDT assay was evaluated in eight different off-label sample types.


Asunto(s)
Infecciones por Citomegalovirus , Citomegalovirus , ADN Viral , Tracto Gastrointestinal , Humanos , Citomegalovirus/aislamiento & purificación , Citomegalovirus/genética , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/virología , ADN Viral/genética , ADN Viral/aislamiento & purificación , Reproducibilidad de los Resultados , Tracto Gastrointestinal/virología , Carga Viral/métodos , Sistema Respiratorio/virología , Líquido del Lavado Bronquioalveolar/virología , Sensibilidad y Especificidad
14.
Nutrients ; 16(11)2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38892725

RESUMEN

Xanthohumol (Xn) is an antioxidant flavonoid mainly extracted from hops (Humulus lupulus), one of the main ingredients of beer. As with other bioactive compounds, their therapeutic potential against different diseases has been tested, one of which is Alzheimer's disease (AD). Adenosine is a neuromodulatory nucleoside that acts through four different G protein-coupled receptors: A1 and A3, which inhibit the adenylyl cyclases (AC) pathway, and A2A and A2B, which stimulate this activity, causing either a decrease or an increase, respectively, in the release of excitatory neurotransmitters such as glutamate. This adenosinergic pathway, which is altered in AD, could be involved in the excitotoxicity process. Therefore, the aim of this work is to describe the effect of Xn on the adenosinergic pathway using cell lines. For this purpose, two different cellular models, rat glioma C6 and human neuroblastoma SH-SY5Y, were exposed to a non-cytotoxic 10 µM Xn concentration. Adenosine A1 and A2A, receptor levels, and activities related to the adenosine pathway, such as adenylate cyclase, protein kinase A, and 5'-nucleotidase, were analyzed. The adenosine A1 receptor was significantly increased after Xn exposure, while no changes in A2A receptor membrane levels or AC activity were reported. Regarding 5'-nucleotidases, modulation of their activity by Xn was noted since CD73, the extracellular membrane attached to 5'-nucleotidase, was significantly decreased in the C6 cell line. In conclusion, here we describe a novel pathway in which the bioactive flavonoid Xn could have potentially beneficial effects on AD as it increases membrane A1 receptors while modulating enzymes related to the adenosine pathway in cell cultures.


Asunto(s)
Adenosina , Flavonoides , Glioma , Humulus , Neuroblastoma , Propiofenonas , Receptor de Adenosina A1 , Humanos , Flavonoides/farmacología , Ratas , Propiofenonas/farmacología , Animales , Adenosina/metabolismo , Adenosina/farmacología , Línea Celular Tumoral , Humulus/química , Neuroblastoma/metabolismo , Neuroblastoma/tratamiento farmacológico , Glioma/metabolismo , Glioma/tratamiento farmacológico , Receptor de Adenosina A1/metabolismo , Transducción de Señal/efectos de los fármacos , Adenilil Ciclasas/metabolismo , Receptor de Adenosina A2A/metabolismo
15.
J Pediatr ; 272: 114084, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38705230

RESUMEN

OBJECTIVE: The objective of this study was to assess the role of T-lymphocyte immune responses in newborns with congenital cytomegalovirus (CMV) infection (cCMV) and their potential association with the development of long-term sequelae. STUDY DESIGN: A multicenter, prospective study from 2017 to 2022 was conducted across 8 hospitals in Spain. Blood samples were collected within the first month of life from neonates diagnosed with cCMV. Intracellular cytokine staining was employed to evaluate the presence of CMV-specific interferon-gamma (IFN-γ)-producing CD8+ and CD4+ T lymphocytes (CMV-IFN-γ-CD8+/CD4+) using flow cytometry. The development of sequelae, including hearing loss and neurologic impairment, was assessed during follow-up. RESULTS: In total, 64 newborns were included; 42 infants (65.6%) had symptomatic cCMV. The median age at the last follow-up visit was 25.3 months (IQR 20.1-34.4). Eighteen infants had long-term sequelae (28.1%), predominantly hearing loss (20.3%) and neurologic disorders (15.6%). No relationship was observed between total count or percentage of CMV-specific IFN-γ-CD8+ or CD4+ lymphocytes and long-term sequelae. Multivariable analysis demonstrated an association between lower total lymphocyte count and long-term sequelae (aOR 0.549, 95% CI: 0.323-0.833), which requires further study. CONCLUSIONS: CMV-specific IFN-γ-CD4+ and CD8+ T-lymphocyte responses in neonates with cCMV were not predictive of long-term sequelae.


Asunto(s)
Infecciones por Citomegalovirus , Humanos , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/complicaciones , Recién Nacido , Estudios Prospectivos , Masculino , Femenino , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD4-Positivos/inmunología , España , Interferón gamma/sangre , Lactante , Estudios de Seguimiento , Inmunidad Celular , Citomegalovirus/inmunología , Pérdida Auditiva/inmunología
16.
Vaccine ; 42(19): 4011-4021, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-38760269

RESUMEN

OBJECTIVE: This study aimed to evaluate the effectiveness of SARS-CoV-2 mRNA vaccines in preventing infection and hospitalization among healthcare workers (HCWs) in the Valencian Community (Spain), considering vaccination timing, dose number, and predominant variant. METHODS: A test-negative case-control design estimated vaccine effectiveness against symptomatic disease and hospitalization due to SARS-CoV-2. HCWs who underwent PCR or antigen testing for SARS-CoV-2 from January 2021 to March 2022 were included. Cases had a positive diagnostic test, while controls had negative tests. Adjusted vaccine effectiveness (aVE) was calculated using the formula: aVE = (1 - Odds ratio) × 100. RESULTS: During the Delta variant's predominance, aVE against infection within 12-120 days post-second dose was 64.8 % (BNT162b2) and 59.4 % (mRNA-1273), declining to 21.2 % and 42.2 %, respectively, after 120 days. For the Omicron variant, aVE within 12-120 days post-second dose was 61.1 % (BNT162b2) and 85.1 % (mRNA-1273), decreasing to 36.7 % and 24.9 %, respectively, after 120 days. After a booster dose of mRNA-1273, aVE was 64.0 % (BNT162b2 recipients) and 65.9 % (initial mRNA-1273 recipients). Regardless of variant, aVE for hospitalization prevention after 2 doses was 87.0 % (BNT162b2) and 89.0 % (mRNA-1273). CONCLUSION: The administration of two doses of Moderna-mRNA-1273 against SARS-CoV-2 in HCWs proved to be highly effective in preventing infections and hospitalizations in the first 120 days after the second dose during the predominance of the Omicron variant. The decline in VE after 120 days since the administration of the second dose was significantly restored by the booster dose administration. This increase in VE was greater for the Pfizer vaccine. COVID-19 hospitalization prevention remained stable with both mRNA vaccines throughout the study period.


Asunto(s)
Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19 , Personal de Salud , Hospitalización , Inmunización Secundaria , SARS-CoV-2 , Eficacia de las Vacunas , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , España/epidemiología , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Masculino , Femenino , Hospitalización/estadística & datos numéricos , Adulto , Persona de Mediana Edad , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Vacuna BNT162/inmunología , Vacuna BNT162/administración & dosificación , Estudios de Casos y Controles , Vacuna nCoV-2019 mRNA-1273/inmunología , Vacunación/métodos
17.
Eur J Clin Microbiol Infect Dis ; 43(7): 1427-1436, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38777919

RESUMEN

PURPOSE: Comparing the performance of commercially available SARS-CoV-2 T-cell immunoassay responses may provide useful information for future observational or intervention studies as well as to their potential customers. METHOD: Whole blood was collected from a total of 183 subjects fully vaccinated against COVID-19: 55 healthy controls (Group 1), 50 hematological patients (Group 2), 50 chronic kidney disease patients (Group 3), and 28 elderly nursing home residents (Group 4). Samples were tested with the Roche Elecsys® IGRA (Interferon-gamma release assay) SARS-CoV-2 test (Roche Diagnostics, Rotkreuz, Switzerland), the Euroimmun SARS-CoV-2 test (Euroimmun, Lubeck, Germany), the SARS-CoV-2 T Cell Analysis Kit (Miltenyi Biotec, Bergisch Gladbach, Germany), and a flow-cytometry for intracellular cytokine (IFN-γ) staining-based immunoassay (FC-ICS). RESULTS: Overall, the Roche Elecsys® assay returned the highest number of positive results (151/179; 84.3%), followed by the Euroimmun test (127/183; 69%), and the FC-ICS (135/179; 75%). The Kappa coefficient of agreement was best between IGRAs (0.64). Most discordant results across assays involved patients from Group 2. Overall, IFN-γ concentrations measured by both IGRAs correlated strongly (rho = 0.78; 95% CI 0.71-0.84; P < 0.001) irrespective of the study group. The frequencies of SARS-CoV-2-reactive IFN-γ T cells and IFN-γ concentrations measured by the IGRAs correlated moderately for CD4+ T cells, however, weakly for CD8+ T cells. SARS-CoV-2-experienced participants displayed stronger responses than SARS-CoV-2-naïve when IGRAs, rather than FC-ICS, were used. CONCLUSION: The SARS-CoV-2 immunoassays evaluated in the present study did not return interchangeable qualitative or quantitative results either in seemingly healthy individuals or in immunosuppressed patients.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Huésped Inmunocomprometido , Ensayos de Liberación de Interferón gamma , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , COVID-19/inmunología , Masculino , Femenino , Persona de Mediana Edad , SARS-CoV-2/inmunología , Ensayos de Liberación de Interferón gamma/métodos , Ensayos de Liberación de Interferón gamma/normas , Anciano , Adulto , Vacunas contra la COVID-19/inmunología , Linfocitos T/inmunología , Anciano de 80 o más Años , Interferón gamma/sangre , Interferón gamma/inmunología , Inmunoensayo/métodos
19.
Bone Marrow Transplant ; 59(8): 1118-1126, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38730040

RESUMEN

In the general population, influenza virus, respiratory syncytial virus, and SARS-CoV-2 are considered the most severe community-acquired respiratory viruses (CARVs). However, allogeneic stem cell transplant (allo-SCT) recipients may also face severe courses from other CARVs. This retrospective study compared outcomes of various CARV lower respiratory tract diseases (LRTD) in 235 adult allo-SCT recipients, excluding co-infection episodes. We included 235 adults allo-SCT recipients experiencing 353 CARV LRTD consecutive episodes (130 rhinovirus, 63 respiratory syncytial virus, 43 influenza, 43 human parainfluenza virus, 23 human metapneumovirus, 19 Omicron SARS-CoV-2, 17 common coronavirus, 10 adenovirus and 5 human bocavirus) between December 2013 and June 2023. Day 100 overall survival ranged from 78% to 90% without significant differences among CARV types. Multivariable analysis of day 100 all-cause mortality identified corticosteroid use of >1 to <30 mg/d [Hazard ratio (HR) 2.45, p = 0.02) and ≥30 mg/d (HR 2.20, p = 0.015) along with absolute lymphocyte count <0.2 × 109/L (HR 5.82, p < 0.001) and number of CARV episodes as a continuous variable per one episode increase (HR 0.48, p = 0.001) as independent risk factors for all-cause mortality. Degree of immunosuppression, rather than intrinsic CARV virulence, has the most significant impact on mortality in allo-SCT recipients with CARV-LRTD.


Asunto(s)
Infecciones del Sistema Respiratorio , Humanos , Masculino , Persona de Mediana Edad , Adulto , Femenino , Estudios Retrospectivos , Infecciones del Sistema Respiratorio/virología , Anciano , Trasplante Homólogo , Trasplante de Células Madre Hematopoyéticas/efectos adversos , COVID-19/mortalidad , COVID-19/terapia , Adulto Joven , Tasa de Supervivencia , SARS-CoV-2
20.
BMC Med Educ ; 24(1): 510, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38720261

RESUMEN

BACKGROUND: Bioinstrumentation is essential to biomedical engineering (BME) undergraduate education and professional practice. Several strategies have been suggested to provide BME students with hands-on experiences throughout the curriculum, promoting their preparedness to pursue careers in industry and academia while increasing their learning and engagement. This paper describes the implementation of challenge-based learning (CBL) in an undergraduate bioinstrumentation blended course over the COVID-19 pandemic. METHODS: The CBL experience was implemented in a third-year bioinstrumentation course from the BME program at Tecnologico de Monterrey. Thirty-nine students enrolled in two sections formed fourteen teams that tackled blended learning activities, including online communication, lab experiments, and in-person CBL activities. Regarding the latter, students were challenged to design, prototype, and test a respiratory or cardiac gating device for radiotherapy. An institutional student opinion survey was used to assess the success of our CBL implementation. RESULTS: Student responses to the end-of-term survey showed that they strongly agreed that this course challenged them to learn new concepts and develop new skills. Furthermore, they rated the student-lecturer interaction very positively despite the blended format. Overall, students assessed their learning experience positively. However, implementing this CBL experience required a substantial time increase in planning, student tutoring, and constant communication between lecturers and the industry partner. CONCLUSION: This work provides an effective instance of CBL for BME education to improve students' learning experience despite decreased resource efficiency. Our claim is supported by the student's performance and the positive feedback from our industrial partner.


Asunto(s)
Ingeniería Biomédica , COVID-19 , Curriculum , Aprendizaje Basado en Problemas , Humanos , Ingeniería Biomédica/educación , SARS-CoV-2 , Pandemias , Educación a Distancia/organización & administración
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