RESUMEN
Background: Acinetobacter baumannii (AB) has emerged as one of the most challenging pathogens worldwide, causing invasive infections in the critically ill patients due to their ability to rapidly acquire resistance to antibiotics. This study aimed to analyze antibiotic resistance genes harbored in AB and non-baumannii Acinetobacter calcoaceticus-baumannii (NB-ACB) complex causing invasive diseases in Korean children. Methods: ACB complexes isolated from sterile body fluid of children in three referral hospitals were prospectively collected. Colistin susceptibility was additionally tested via broth microdilution. Whole genome sequencing was performed and antibiotic resistance genes were analyzed. Results: During January 2015 to December 2020, a total of 67 ACB complexes were isolated from sterile body fluid of children in three referral hospitals. The median age of the patients was 0.6 (interquartile range, 0.1-7.2) years old. Among all the isolates, 73.1% (n=49) were confirmed as AB and others as NB-ACB complex by whole genome sequencing. Among the AB isolates, only 22.4% susceptible to carbapenem. In particular, all clonal complex (CC) 92 AB (n=33) showed multi-drug resistance, whereas 31.3% in non-CC92 AB (n=16) (P<0.001). NB-ACB showed 100% susceptibility to all classes of antibiotics except 3rd generation cephalosporin (72.2%). The main mechanism of carbapenem resistance in AB was the bla oxa23 gene with ISAba1 insertion sequence upstream. Presence of pmr gene and/or mutation of lpxA/C gene were not correlated with the phenotype of colistin resistance of ACB. All AB and NB-ACB isolates carried the abe and ade multidrug efflux pumps. Conclusions: In conclusion, monitoring and research for resistome in ACB complex is needed to identify and manage drug-resistant AB, particularly CC92 AB carrying the bla oxa23 gene.
Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Antibacterianos , Pruebas de Sensibilidad Microbiana , Secuenciación Completa del Genoma , Humanos , Niño , Preescolar , Lactante , República de Corea/epidemiología , Infecciones por Acinetobacter/microbiología , Infecciones por Acinetobacter/epidemiología , Acinetobacter baumannii/genética , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/aislamiento & purificación , Antibacterianos/farmacología , Femenino , Masculino , COVID-19/epidemiología , Colistina/farmacología , Acinetobacter calcoaceticus/genética , Acinetobacter calcoaceticus/efectos de los fármacos , Acinetobacter calcoaceticus/aislamiento & purificación , Farmacorresistencia Bacteriana/genética , Farmacorresistencia Bacteriana Múltiple/genética , SARS-CoV-2/genética , SARS-CoV-2/efectos de los fármacos , Estudios Prospectivos , beta-Lactamasas/genética , beta-Lactamasas/metabolismoRESUMEN
The Korean Society of Infectious Diseases has been regularly developing guidelines for adult immunization since 2007. In 2023, the guidelines for the following seven vaccines were revised: influenza, herpes zoster, pneumococcal, tetanus-diphtheria-pertussis (Tdap), human papillomavirus (HPV), meningococcal, and rabies vaccines. For the influenza vaccine, a recommendation for enhanced vaccines for the elderly was added. For the herpes zoster vaccine, a recommendation for the recombinant zoster vaccine was added. For the pneumococcal vaccine, the current status of the 15-valent pneumococcal conjugate vaccine and 20-valent PCV was described. For the Tdap vaccine, the possibility of using Tdap instead of tetanus-diphtheria vaccine was described. For the HPV vaccine, the expansion of the eligible age for vaccination was described. For the meningococcal vaccine, a recommendation for the meningococcal B vaccine was added. For the rabies vaccine, the number of pre-exposure prophylaxis doses was changed. This manuscript documents the summary and rationale of the revisions for the seven vaccines. For the vaccines not mentioned in this manuscript, the recommendations in the 3rd edition of the Vaccinations for Adults textbook shall remain in effect.
RESUMEN
BACKGROUND: Antimicrobial resistance (AMR), driven by inappropriate and overuse of antibiotics, poses a significant threat, especially to patients with acute leukaemia. OBJECTIVES: To evaluate the impact of antimicrobial stewardship programmes (ASPs) on antibiotic use and analyse temporal changes in bloodstream infections (BSI) caused by AMR organisms. METHODS: We performed a retrospective, interventional, longitudinal cohort study spanning an 11-year period. ASPs included optimizing antibiotic use, enhancing tracking and reporting systems and delineating leadership and accountability. A segmented regression model of interrupted time series was used to evaluate the trend of antibiotic consumption and BSI with AMR organisms after the interventions. RESULTS: A total of 3296 BSI episodes with 454â419â days of therapy (DOT) from 7754 patients were obtained. ASPs were significantly associated with an immediate reduction [-70.03 DOT/1000 patient-days (PD), Pâ=â0.036] and a decreasing trend (-11.65 DOT/1000 PD per quarter, Pâ<â0.001) in overall antibiotic use. The increasing incidence of BSI with AMR before ASP intervention was notably curbed and revealed a decreasing trend (slope change: -0.06 BSI/1000 PD per quarter, Pâ=â0.002). The decreasing trend was more significant for Enterobacterales: ciprofloxacin-resistant and ESBL-producing isolates showed a slope change of -0.06 BSI/1000 PD and -0.08 BSI/1000 PD per quarter, respectively (all Pâ<â0.05). However, Pseudomonas aeruginosa BSI increased. CONCLUSIONS: Multidimensional ASPs effectively reduced both the immediate and trends in overall antibiotic usage even in patients with acute leukaemia. Additionally, there was a notable decrease in the incidence of BSI caused by AMR organisms, particularly among Enterobacterales.
Asunto(s)
Antibacterianos , Programas de Optimización del Uso de los Antimicrobianos , Análisis de Series de Tiempo Interrumpido , Humanos , Estudios Longitudinales , Antibacterianos/uso terapéutico , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Farmacorresistencia Bacteriana , Leucemia/tratamiento farmacológico , Leucemia/complicaciones , Utilización de Medicamentos/estadística & datos numéricos , Utilización de Medicamentos/normasRESUMEN
The antimicrobial activity of the natural compounds from plant and food have well discovered since the interest on the beneficial effect of the natural compounds was risen. Quercetin, a flavonoid derived from vegetables, including onions, red leaf lettuces and cherries has been studied for diverse biological characteristics as anti-cancer and anti-microbial activities. The aim of current study is to investigate the specific antibacterial modes of action of quercetin against Escherichia coli. Quercetin decreased the E. coli cell viability and induced the severe damages (oxidative stress, DNA fragmentation) leading to cell death. Reactive oxygen species (ROS) generation was observed during the process, which we confirmed that oxidative stress was the key action of antibacterial activity of quercetin exerting its influence potently. Based on the results of Annexin V and Caspace FITC-VAD-FMK assay, the oxidative damage in E. coli has led to the bacterial apoptosis-like death in E. coli. To sum up, the contribution of ROS generation exerts crucial impact in antibacterial activity of quercetin.
Asunto(s)
Antibacterianos , Apoptosis , Escherichia coli , Viabilidad Microbiana , Estrés Oxidativo , Quercetina , Especies Reactivas de Oxígeno , Quercetina/farmacología , Escherichia coli/efectos de los fármacos , Escherichia coli/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Antibacterianos/farmacología , Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Viabilidad Microbiana/efectos de los fármacos , Fragmentación del ADN/efectos de los fármacos , Pruebas de Sensibilidad MicrobianaRESUMEN
Antimicrobial stewardship programs (ASPs) can lower antibiotic use, decrease medical expenses, prevent the emergence of resistant bacteria, and enhance treatment for infectious diseases. This study summarizes the stepwise implementation and effects of ASPs in a single university-affiliated tertiary care hospital in Korea; it also presents future directions and challenges in resource-limited settings. At the study hospital, the core elements of the ASP such as leadership commitment, accountability, and operating system were established in 2000, then strengthened by the formation of the Antimicrobial Stewardship (AMS) Team in 2018. The actions of ASPs entail key components including a computerized restrictive antibiotic prescription system, prospective audit, post-prescription review through quantitative and qualitative intervention, and pharmacy-based interventions to optimize antibiotic usage. The AMS Team regularly tracked antibiotic use, the effects of interventions, and the resistance patterns of pathogens in the hospital. The reporting system was enhanced and standardized by participation in the Korea National Antimicrobial Use Analysis System, and educational efforts are ongoing. Stepwise implementation of the ASP and the efforts of the AMS Team have led to a substantial reduction in the overall consumption of antibiotics, particularly regarding injectables, and optimization of antibiotic use. Our experience highlights the importance of leadership, accountability, institution-specific interventions, and the AMS Team.
Asunto(s)
Antibacterianos , Programas de Optimización del Uso de los Antimicrobianos , Hospitales Universitarios , Centros de Atención Terciaria , Humanos , Antibacterianos/uso terapéutico , Programas de Optimización del Uso de los Antimicrobianos/organización & administración , Farmacorresistencia Bacteriana , Revisión de la Utilización de Medicamentos , Hospitales Universitarios/organización & administración , Pautas de la Práctica en Medicina/normas , Desarrollo de Programa , Evaluación de Programas y Proyectos de Salud , República de Corea , Centros de Atención Terciaria/organización & administración , Centros de Atención Terciaria/normasRESUMEN
BACKGROUND/AIMS: Since the coronavirus disease 2019 (COVID-19) outbreak, hospitals have implemented infection control measures to minimize the spread of the virus within facilities. This study aimed to investigate the impact of COVID-19 on the incidence of healthcare-associated infections (HCAIs) and common respiratory virus (cRV) infections in hematology units. METHODS: This retrospective study included all patients hospitalized in Catholic Hematology Hospital between 2019 and 2020. Patients infected with vancomycin-resistant Enterococci (VRE), carbapenemase-producing Enterobacterales (CPE), Clostridium difficile infection (CDI), and cRV were analyzed. The incidence rate ratio (IRR) methods and interrupted time series analyses were performed to compare the incidence rates before and after the pandemic. RESULTS: The incidence rates of CPE and VRE did not differ between the two periods. However, the incidence of CDI increased significantly (IRR: 1.41 [p = 0.002]) after the COVID-19 pandemic. The incidence of cRV infection decreased by 76% after the COVID-19 outbreak (IRR: 0.240 [p < 0.001]). The incidence of adenovirus, parainfluenza virus, and rhinovirus infection significantly decreased in the COVID-19 period (IRRs: 0.087 [p = 0.003], 0.031 [p < 0.001], and 0.149 [p < 0.001], respectively). CONCLUSION: The implementation of COVID-19 infection control measures reduced the incidence of cRV infection. However, CDI increased significantly and incidence rates of CPE and VRE remained unchanged in hematological patients after the pandemic. Infection control measures suitable for each type of HCAI, such as stringent hand washing for CDI and enough isolation capacities, should be implemented and maintained in future pandemics, especially in immunocompromised patients.
Asunto(s)
COVID-19 , Infección Hospitalaria , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Incidencia , Estudios Retrospectivos , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Infección Hospitalaria/diagnóstico , Infección Hospitalaria/microbiología , República de Corea/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Control de Infecciones , Anciano , Adulto , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/diagnóstico , Hematología , SARS-CoV-2RESUMEN
OBJECTIVES: This study aimed to identify the cause of false-positive serum Aspergillus antigen galactomannan (GM) results in our centre. METHODS: We performed a case-control study aiming to elucidate the factors associated with false-positive GM results. Independent risk factors for false-positive GM were evaluated through a multivariable regression analysis. An interrupted time series analysis was used to evaluate the effectiveness of an intervention removing the identified factors. RESULTS: Among 568 patients tested, GM was positive in 130 patients of whom 97 had false-positive GM (cases). These were compared with 427 patients with true-negative GM (controls). Administration of dextrose-containing fluids within 6 days before GM testing was an independent predictor for false-positive GM results (adjusted odds ratio [aOR], 18.60; 95% CI, 8.95-38.66. An analysis of GM presence in different dextrose-containing fluids revealed positivity in 34.8% (8 of 23) (manufacturer A) and 33.3% (5 of 15) (manufacturer B) of the samples. Investigation of the manufacturing process revealed that the saccharification process employed enzymes derived from Aspergillus niger. After identifying the root cause of false positivity, GM-containing dextrose fluid use was restricted. Interrupted time series analysis showed an immediate reduction of GM false-positivity (-6.5% per week, p = 0.045) and a declining trend (-0.33% per week, p = 0.005) postintervention. CONCLUSIONS: Administering dextrose-containing fluids was the primary factor causing false-positive serum Aspergillus antigen GM assay results. Our investigation led to a modification of the manufacturing process of the dextrose-containing fluids.
Asunto(s)
Antígenos Fúngicos , Aspergilosis , Galactosa/análogos & derivados , Glucosa , Análisis de Series de Tiempo Interrumpido , Mananos , Humanos , Mananos/sangre , Estudios de Casos y Controles , Glucosa/análisis , Reacciones Falso Positivas , Femenino , Masculino , Persona de Mediana Edad , Anciano , Antígenos Fúngicos/sangre , Aspergilosis/diagnóstico , Aspergilosis/sangre , Adulto , Aspergillus/inmunología , Aspergillus/aislamiento & purificación , Factores de Riesgo , Aspergillus nigerRESUMEN
BACKGROUND: The adjuvanted RSV prefusion F protein-based vaccine (RSVPreF3 OA) was efficacious against RSV-related lower respiratory tract disease (RSV-LRTD) in ≥60-years-olds over 1 RSV season. We evaluated efficacy and safety of 1 RSVPreF3 OA dose and of 2 RSVPreF3 OA doses given 1 year apart against RSV-LRTD over 2 RSV seasons post-dose 1. METHODS: In this phase 3, blinded trial, ≥60-year-olds were randomized (1:1) to receive RSVPreF3 OA or placebo pre-season 1. RSVPreF3 OA recipients were re-randomized (1:1) to receive a second RSVPreF3 OA dose (RSV_revaccination group) or placebo (RSV_1dose group) pre-season 2; participants who received placebo pre-season 1 received placebo pre-season 2 (placebo group). Efficacy of both vaccine regimens against RSV-LRTD was evaluated over 2 seasons combined (confirmatory secondary objective, success criterion: lower limits of 2-sided CIs around efficacy estimates >20%). RESULTS: The efficacy analysis comprised 24 967 participants (RSV_1dose: 6227; RSV_revaccination: 6242; placebo: 12 498). Median efficacy follow-up was 17.8 months. Efficacy over 2 seasons of 1 RSVPreF3 OA dose was 67.2% (97.5% CI: 48.2-80.0%) against RSV-LRTD and 78.8% (95% CI: 52.6-92.0%) against severe RSV-LRTD. Efficacy over 2 seasons of a first dose followed by revaccination was 67.1% (97.5% CI: 48.1-80.0%) against RSV-LRTD and 78.8% (95% CI: 52.5-92.0%) against severe RSV-LRTD. Reactogenicity/safety of the revaccination dose were similar to dose 1. CONCLUSIONS: One RSVPreF3 OA dose was efficacious against RSV-LRTD over 2 RSV seasons in ≥60-year-olds. Revaccination 1 year post-dose 1 was well tolerated but did not seem to provide additional efficacy benefit in the overall study population. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov: NCT04886596.
Asunto(s)
Infecciones por Virus Sincitial Respiratorio , Vacunas contra Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Proteínas Virales de Fusión , Humanos , Infecciones por Virus Sincitial Respiratorio/prevención & control , Vacunas contra Virus Sincitial Respiratorio/inmunología , Vacunas contra Virus Sincitial Respiratorio/administración & dosificación , Vacunas contra Virus Sincitial Respiratorio/efectos adversos , Masculino , Femenino , Virus Sincitial Respiratorio Humano/inmunología , Anciano , Persona de Mediana Edad , Proteínas Virales de Fusión/inmunología , Anticuerpos Antivirales/sangre , Anciano de 80 o más Años , Estaciones del Año , Eficacia de las Vacunas , Método Doble Ciego , Inmunización SecundariaRESUMEN
AIMS: The purpose of this paper was to demonstrate the antimicrobial activity of urechistachykinin I (LRQSQFVGSR-NH2) extracted from Urechis unicinctus,and its mode of action dependent on mitochondrial dysfunction. METHODS AND RESULTS: The antifungal activity of urechistachykinin I generated reactive oxygen species (ROS), as demonstrated with MitoSOX Red and hydroxyphenyl fluorescein (HPF). Overaccumulation of ROS caused oxidative damage to cells by inducing mitochondrial dysfunction. Mitochondrial disruption resulted in cell death, creating several hallmarks that included lipid peroxidation, glutathione oxidation, and depolarization. Moreover, the loss of mitochondria changed the calcium ion imbalance by depolarization of the mitochondrial membrane. In particular, iron accumulation and DNA fragmentation measurement determined the type of cell death. Our results indicate that urechistachykinin I treatment induced ferroptosis-like death in Saccharomyces cerevisiae via mitochondrial dysfunction. CONCLUSIONS: Urechistachykinin I treatment induced mitochondrial dysfunction in S. cerevisiae by generating ROS, and the subsequent oxidative damage caused the ferroptosis-like cell death.
Asunto(s)
Ferroptosis , Enfermedades Mitocondriales , Neuropéptidos , Humanos , Saccharomyces cerevisiae/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: Older adults with chronic cardiorespiratory or endocrine/metabolic conditions are at increased risk of respiratory syncytial virus (RSV)-related acute respiratory illness (RSV-ARI) and severe respiratory disease. In an ongoing, randomized, placebo-controlled, multicountry, phase 3 trial in ≥60-year-old participants, an AS01E-adjuvanted RSV prefusion F protein-based vaccine (RSVPreF3 OA) was efficacious against RSV-related lower respiratory tract disease (RSV-LRTD), severe RSV-LRTD, and RSV-ARI. We evaluated efficacy and immunogenicity among participants with coexisting cardiorespiratory or endocrine/metabolic conditions that increase the risk of severe RSV disease ("conditions of interest"). METHODS: Medically stable ≥60-year-old participants received 1 dose of RSVPreF3 OA or placebo. Efficacy against first RSV-LRTD and RSV-ARI episodes was assessed in subgroups with/without coexisting cardiorespiratory or endocrine/metabolic conditions of interest. Immunogenicity was analyzed post hoc in these subgroups. RESULTS: In total, 12 467 participants received RSVPreF3 OA and 12 499 received placebo. Of these, 39.6% (RSVPreF3 OA) and 38.9% (placebo) had ≥1 coexisting condition of interest. The median efficacy follow-up was 6.7 months. Efficacy against RSV-LRTD was high in participants with ≥1 condition of interest (94.6%), ≥1 cardiorespiratory (92.1%), ≥1 endocrine/metabolic (100%), and ≥2 conditions of interest (92.0%). Efficacy against RSV-ARI was 81.0% in participants with ≥1 condition of interest (88.1% for cardiorespiratory, 79.4% for endocrine/metabolic conditions) and 88.0% in participants with ≥2 conditions of interest. Postvaccination neutralizing titers were at least as high in participants with ≥1 condition of interest as in those without. CONCLUSIONS: RSVPreF3 OA was efficacious against RSV-LRTD and RSV-ARI in older adults with coexisting medical conditions associated with an increased risk of severe RSV disease. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov: NCT04886596.
Asunto(s)
Infecciones por Virus Sincitial Respiratorio , Vacunas contra Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Humanos , Anciano , Persona de Mediana Edad , Vacunas contra Virus Sincitial Respiratorio/efectos adversos , Anticuerpos Antivirales , Anticuerpos Neutralizantes , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/prevención & controlRESUMEN
INTRODUCTION: To estimate herpes zoster (HZ) incidence rate (IR) and economic burden in individuals with immunocompromised conditions and autoimmune diseases (IC/AID) in the Republic of Korea (ROK). METHODS: The nationwide Health Insurance Review and Assessment Service database was used to identify HZ cases from 2016 to 2020 in ROK. HZ and non-HZ IC/AID cases were matched 1:3 using age, sex, institution, Charlson comorbidity index, IC/AID, and index date. Annual HZ IRs/1000 persons and 1-year HZ-associated all-cause direct medical costs for IC/AID cases were calculated. RESULTS: Among 65,976 individuals with IC/AID (mean age 57.14 years [standard deviation 14.1]; 64.94% female), annual HZ IR (95% confidence interval) fluctuated from 2016 to 2020, averaging 23.41/1000 persons (22.21-24.62) and was higher in women (26.85 [25.40-28.31]) than men (18.96 [18.03-19.89]). IRs were highest in individuals aged ≥ 50 years, and in those with transplants (including solid organ and hematopoietic stem cell transplants; 37.12 [35.45-38.79]) and hemato-oncology conditions (35.5 [31.6-39.3]). Mean 12-month all-cause direct medical costs were higher in individuals with IC/AID and HZ (4,759,671 Korean Republic won [KRW]; approximately 4046 United States dollar [USD; according to the 2020 conversion rate from UNCTAD; 1 KRW = 0.00085 USD]) than those without HZ (3,786,658 KRW; 3219 USD). CONCLUSION: Individuals with IC/AID have a substantial disease and economic burden from HZ in ROK, highlighting the need for appropriate HZ prevention measures in the IC/AID population.
RESUMEN
The ß-tubulin (benA) gene is a promising target for the identification of Aspergillus species. Assessment of the clinical implementation and performance of benA gene-based Aspergillus polymerase chain reaction (PCR) remains warranted. In this study, we assessed the analytical performance of the BenA probe PCR in comparison with the Aspergenius kit. We prospectively collected bronchoalveolar lavage (BAL) fluid via diagnostic bronchoscopy from adult patients with hematologic diseases. BenA gene-based multiplex real-time PCR and sequential melting temperature analysis were performed to detect the azole resistance of Aspergillus fumigatus. In total, 76 BAL fluids in 75 patients suspicious of invasive pulmonary aspergillosis (IPA) were collected. Before the application of PCR, the prevalence of proven and probable IPA was 32.9%. However, after implementing the benA gene-based PCR, 15.8% (12 out of 76) of potential IPA cases were reclassified as probable IPA. The analytical performance of the BenA probe PCR in BAL samples was comparable to that of the Aspergenius kit. The diagnostic performance was as follows: sensitivity, 52.0%; specificity, 64.7%; positive predictive value, 41.9%; negative predictive value, 73.3%; positive likelihood ratio, 1.473; and negative likelihood ratio, 0.741. Moreover, benA gene-based Aspergillus PCR discriminated all major sections of Aspergillus, including cryptic species such as Aspergillus tubingensis. Sequential melting temperature analysis successfully detected 2 isolates (15.4%) of A. fumigatus carrying resistant mutations. BenA gene-based Aspergillus PCR with melting temperature analysis enhances diagnostic accuracy and detects not only cryptic species but also resistant mutations of A. fumigatus. It shows promise for clinical applications in the diagnosis of IPA.
RESUMEN
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a complex systemic autoimmune disease characterized by small vessel vasculitis. Typically, the relapse rate is lower in patients with end-stage kidney disease (ESKD) than in those with chronic kidney disease, prior to dialysis. Here, we report a rare case of multi-organ relapse in a patient with myeloperoxidase (MPO)-AAV who underwent hemodialysis following coronavirus disease 2019 (COVID-19). A man in his 70s with type 2 diabetes and hypertension was undergoing maintenance hemodialysis for ESKD resulting from MPO-AAV glomerulonephritis. Following severe acute respiratory syndrome coronavirus 2 infection, the patient was hospitalized for persistent nausea and vomiting. No significant findings were observed, including in endoscopy. However, the patient experienced severe symptoms that hindered oral intake and was refractory to pharmacological therapy. Additionally, despite receiving antibiotics and antituberculosis treatment, the patient experienced persistent unexplained pleural effusion. Moreover, the patient's level of consciousness rapidly deteriorated during hospitalization. Although C-reactive protein levels and MPO-ANCA titers were elevated, no evidence of infection was detected on brain imaging or cerebrospinal fluid analysis. Therefore, we diagnosed this case as a relapse of AAV and promptly administered methylprednisolone pulse therapy and rituximab. Subsequently, all aforementioned symptoms in the patient improved, and the current ANCA levels remain negative. Thus, the relapse of AAV after COVID-19 is rare; however, it can present in several ways in patients undergoing dialysis. Therefore, clinicians should closely monitor ANCA titers and subtle symptoms, even in patients with dialysis-dependent AAV.
RESUMEN
Assessing immune responses post-SARS-CoV-2 vaccination is crucial for optimizing vaccine strategies. This prospective study aims to evaluate immune responses and breakthrough infection in 235 infection-naïve healthcare workers up to 13-15 months after initial vaccination in two vaccine groups (108 BNT/BNT/BNT and 127 ChAd/ChAd/BNT). Immune responses were assessed using the interferon-gamma enzyme-linked immunospot (ELISPOT) assay, total immunoglobulin, and neutralizing activity through surrogate virus neutralization test at nine different time points. Both groups exhibited peak responses one to two months after the second or third dose, followed by gradual declines over six months. Notably, the ChAd group exhibited a gradual increase in ELISPOT results, but their antibody levels declined more rapidly after reaching peak response compared to the BNT group. Six months after the third dose, both groups had substantial cellular responses, with superior humoral responses in the BNT group (p < 0.05). As many as 55 breakthrough infection participants displayed higher neutralization activities against Omicron variants, but similar cellular responses compared to 127 infection-naïve individuals, suggesting cross-immunity. Distinct neutralization classifications (<30%, >80% inhibition) correlated with different ELISPOT results. Our study reveals diverse immune response patterns based on vaccine strategies and breakthrough infections, emphasizing the importance of understanding these dynamics for optimized vaccination decisions.
RESUMEN
Antimicrobial peptides (AMPs), such as urechistachykinin I (LRQSQFVGSR-NH2), derived from urechis unicinctus, have demonstrated antimicrobial activities. It exhibits low cytotoxicity and selectivity between microbial and mammalian cells suggesting its potent antimicrobial ability. However, the underlying antimicrobial mechanisms remain unknown. Herein, we elucidated the antibacterial action against Vibrio vulnificus, focusing on the reactive oxygen species (ROS). ROS is crucial for antibiotic-mediated killing and oxidative stress. After treatment with urechistachykinin I, superoxide anions and hydroxyl radicals increase, and the overproduction of ROS leads to oxidative damage and destruction of the redox system. Oxidation of the defense system like glutathione or glutathione peroxidase 4 illustrates the dysfunction of cellular metabolism and induces lipid peroxidation attributed to depolarization and integrity brokerage. Cell death demonstrated these properties, and additional experiments, including iron accumulation, liperfluo, and DNA fragmentation, were promoted. The results demonstrated that urechistachykinin I-induced ferroptosis-like death in Vibrio vulnificus is dependent on ROS production. KEY POINTS: ⢠Urechistachykinin I induce reactive oxygen species production ⢠Urechistachykinin I cause oxidative damaged on the V. vulnificus ⢠Urechistachykinin I ferroptosis-like death in V. vulnificus.
Asunto(s)
Antiinfecciosos , Ferroptosis , Vibrio vulnificus , Animales , Especies Reactivas de Oxígeno/metabolismo , Vibrio vulnificus/metabolismo , Mamíferos/metabolismoRESUMEN
The evolution of defects during perovskite film fabrication deteriorates the overall film quality and adversely affects the device efficiency of perovskite solar cells (PSCs). We endeavored to control the formation of defects by applying an additive engineering strategy using FABr, which retards the crystal growth formation of CsPbI2.2Br0.8 perovskite by developing an intermediate phase at the initial stage. Improved crystalline and pinhole-free perovskite film with an optimal concentration of FABr-0.8M% additive was realized through crystallographic and microscopic analysis. Suppressed non-radiative recombination was observed through photoluminescence with an improved lifetime of 125 ns for FABr-0.8M% compared to the control film (83 ns). The champion device efficiency of 17.95% was attained for the FABr-0.8M% PSC, while 15.94% efficiency was achieved in the control PSC under air atmospheric conditions. Furthermore, an impressively high indoor performance of 31.22% was achieved for the FABr-0.8M% PSC under 3200 K (1000 lux) LED as compared to the control (23.15%). With a realistic approach of air processing and controlling the crystallization kinetics in wide-bandgap halide PSCs, this investigation paves the way for implementing additive engineering strategies to reduce defects in halide perovskites, which can further benefit efficiency enhancements in outdoor and indoor applications.
RESUMEN
The prevention and management of cytomegalovirus (CMV) reactivation is important to improve the outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) recipients. The aim of this study was to analyze real-world data regarding the incidence and characteristics of CMV infections until 1 year after allo-HCT under 100-day letermovir prophylaxis. A single-center retrospective study was conducted between November 2020 and October 2021. During the study period, 358 patients underwent allo-HCT, 306 of whom received letermovir prophylaxis. Cumulative incidence of clinically significant CMV infection (CS-CMVi) was 11.4%, 31.7%, and 36.9% at 14 weeks, 24 weeks, and 1 year post-HCT, respectively. Through multivariate analysis, the risk of CS-CMVi increased with graft-versus-host disease (GVHD) ≥ grade 2 (adjusted odds ratio 3.640 [2.036-6.510]; p < 0.001). One-year non-relapse mortality was significantly higher in letermovir breakthrough CS-CMVi patients than those with subclinical CMV reactivation who continued receiving letermovir (p = 0.002). There were 18 (15.9%) refractory CMV infection cases in this study population. In summary, letermovir prophylaxis is effective at preventing CS-CMVi until day 100, which increased after the cessation of letermovir. GVHD is still a significant risk factor in the era of letermovir prophylaxis. Further research is needed to establish individualized management strategies, especially in patients with significant GVHD or letermovir breakthrough CS-CMVi.
Asunto(s)
Infecciones por Citomegalovirus , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Estudios de Seguimiento , Estudios Retrospectivos , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/etiología , Infecciones por Citomegalovirus/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/prevención & controlRESUMEN
BACKGROUND AND OBJECTIVE: A double-blind phase 3 study was conducted to compare posaconazole 300 mg intravenously (IV)/300 mg orally once daily (twice daily day 1) with voriconazole 4 mg/kg IV twice daily/200 mg orally twice daily (6 mg/kg day 1) for treatment of invasive aspergillosis. This analysis was conducted to summarize the pharmacokinetics and exposure-response relationships of posaconazole and voriconazole using plasma trough concentration (Ctrough) as a surrogate for exposure from the double-blind phase 3 study. METHODS: The pharmacokinetic evaluable population included all intention-to-treat (ITT) participants with at least one plasma concentration during the treatment period. Treatment blinding was maintained without therapeutic drug monitoring. Ctrough sampling occurred throughout treatment; efficacy and safety were evaluated using quartiles determined by mean Ctrough concentrations. Exposure efficacy variables included day 42 all-cause mortality (primary study endpoint) and global clinical response. Exposure safety variables included all adverse events and treatment-related adverse events. RESULTS: The pharmacokinetic analysis population included 506 of 575 ITT participants (437 with Ctrough concentrations: 228 posaconazole, 209 voriconazole). No trend was seen across quartiles of posaconazole Ctrough for the key efficacy endpoint of all-cause mortality through day 42. Participants in the highest quartile of voriconazole Ctrough had higher all-cause mortality through day 42 than participants in the lower three quartiles of voriconazole Ctrough. Similar findings were observed for global clinical response and Ctrough. No clear exposure safety trend by quartile was seen for posaconazole or voriconazole. CONCLUSIONS: A strong exposure-response relationship was not observed across the range of exposure from the administered doses and formulations for posaconazole or voriconazole. TRIAL REGISTRATION: NCT01782131; registered January 30, 2013.
Asunto(s)
Aspergilosis , Triazoles , Humanos , Voriconazol/efectos adversos , Triazoles/efectos adversos , Aspergilosis/tratamiento farmacológico , Método Doble CiegoRESUMEN
The ongoing coronavirus disease 2019 (COVID-19) pandemic demands rapid and straightforward diagnostic tools to prevent early-stage viral transmission. Although nasopharyngeal swabs are a widely used patient sample collection method for diagnosing COVID-19, using these samples for diagnosis without RNA extraction increases the risk of obtaining false-positive and -negative results. Thus, multiple purification steps are necessary, which are time-consuming, generate significant waste, and result in substantial sample loss. To address these issues, we developed surface-modified polymerase chain reaction (PCR) tubes using the tertiary aminated polymer poly(2-dimethylaminomethylstyrene) (pDMAMS) via initiated chemical vapor deposition. Introducing the clinical samples into the pDMAMS-coated tubes resulted in approximately 100% RNA capture efficiency within 25 min, which occurred through electrostatic interactions between the positively charged pDMAMS surface and the negatively charged RNA. The captured RNA is then detected via chamber digital PCR, enabling a sensitive, accurate, and rapid diagnosis. Our platform provides a simple and efficient RNA extraction and detection strategy that allows detection from 22 nasopharyngeal swabs and 21 saliva specimens with 0% false negatives. The proposed method can facilitate the diagnosis of COVID-19 and contribute to the prevention of early-stage transmission.