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1.
Immunity ; 54(1): 44-52.e3, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33338412

RESUMO

Memory T cell responses have been demonstrated in COVID-19 convalescents, but ex vivo phenotypes of SARS-CoV-2-specific T cells have been unclear. We detected SARS-CoV-2-specific CD8+ T cells by MHC class I multimer staining and examined their phenotypes and functions in acute and convalescent COVID-19. Multimer+ cells exhibited early differentiated effector-memory phenotypes in the early convalescent phase. The frequency of stem-like memory cells was increased among multimer+ cells in the late convalescent phase. Cytokine secretion assays combined with MHC class I multimer staining revealed that the proportion of interferon-γ (IFN-γ)-producing cells was significantly lower among SARS-CoV-2-specific CD8+ T cells than those specific to influenza A virus. Importantly, the proportion of IFN-γ-producing cells was higher in PD-1+ cells than PD-1- cells among multimer+ cells, indicating that PD-1-expressing, SARS-CoV-2-specific CD8+ T cells are not exhausted, but functional. Our current findings provide information for understanding of SARS-CoV-2-specific CD8+ T cells elicited by infection or vaccination.


Assuntos
Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , Receptor de Morte Celular Programada 1/metabolismo , SARS-CoV-2/imunologia , Reação de Fase Aguda/imunologia , Reação de Fase Aguda/virologia , COVID-19/patologia , COVID-19/virologia , Convalescença , Epitopos de Linfócito T , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Memória Imunológica , Imunofenotipagem , Interferon gama/metabolismo , Ativação Linfocitária , Carga Viral
2.
N Engl J Med ; 384(9): 795-807, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33306283

RESUMO

BACKGROUND: Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known. METHODS: We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients received remdesivir (≤10 days) and either baricitinib (≤14 days) or placebo (control). The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15. RESULTS: A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval [CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P = 0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0% vs. 21.0%; difference, -5.0 percentage points; 95% CI, -9.8 to -0.3; P = 0.03), as were new infections (5.9% vs. 11.2%; difference, -5.3 percentage points; 95% CI, -8.7 to -1.9; P = 0.003). CONCLUSIONS: Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04401579.).


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Azetidinas/uso terapêutico , Tratamento Farmacológico da COVID-19 , Purinas/uso terapêutico , Pirazóis/uso terapêutico , Sulfonamidas/uso terapêutico , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/uso terapêutico , Adulto , Idoso , Alanina/efeitos adversos , Alanina/uso terapêutico , Antivirais/efeitos adversos , Azetidinas/efeitos adversos , COVID-19/mortalidade , COVID-19/terapia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Inibidores de Janus Quinases/efeitos adversos , Inibidores de Janus Quinases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Oxigenoterapia , Purinas/efeitos adversos , Pirazóis/efeitos adversos , Respiração Artificial , Sulfonamidas/efeitos adversos , Resultado do Tratamento
3.
J Korean Med Sci ; 39(4): e19, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38288533

RESUMO

BACKGROUND: Mpox is a viral illness with a characteristic skin rash caused by the monkeypox virus. In 2022, Mpox spread throughout the world, and an epidemic through domestic transmission started in South Korea in early 2023. This study aimed to summarize the clinical features of Mpox patients in South Korea. METHODS: This is a multicenter retrospective study conducted at four hospitals in South Korea. All adult patients diagnosed with Mpox who were admitted to the study hospitals between June 1, 2022 and May 26, 2023 and were discharged by June 30, 2023 were reviewed. RESULTS: Sixty patients were included, accounting for 65.9% of Mpox cases reported in South Korea during the study period. Median age was 32 years and 97% (58/60) of patients were male. In total, 85% (51/60) of patients reported their sexual orientation as homosexual or bisexual. The most common route of transmission was sexual or close contact (55/60). Every patient had a skin rash and 88% (53/60) had constitutional symptoms. In total, 42% (25/60) of patients had human immunodeficiency virus and 25% (15/60) had concomitant sexually transmitted infections. Severe manifestations of Mpox were identified in only two patients. CONCLUSION: Mpox patients in South Korea were mainly young adult males and were infected through sexual contact. The clinical outcomes were favorable.


Assuntos
Exantema , Mpox , Adulto Jovem , Humanos , Feminino , Masculino , Adulto , Estudos Retrospectivos , República da Coreia/epidemiologia , Comportamento Sexual , Exantema/etiologia
4.
J Korean Med Sci ; 39(12): e118, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38565175

RESUMO

BACKGROUND: Since the emergence of hypervirulent strains of Clostridioides difficile, the incidence of C. difficile infections (CDI) has increased significantly. METHODS: To assess the incidence of CDI in Korea, we conducted a prospective multicentre observational study from October 2020 to October 2021. Additionally, we calculated the incidence of CDI from mass data obtained from the Health Insurance Review and Assessment Service (HIRA) from 2008 to 2020. RESULTS: In the prospective study with active surveillance, 30,212 patients had diarrhoea and 907 patients were diagnosed with CDI over 1,288,571 patient-days and 193,264 admissions in 18 participating hospitals during 3 months of study period; the CDI per 10,000 patient-days was 7.04 and the CDI per 1,000 admission was 4.69. The incidence of CDI was higher in general hospitals than in tertiary hospitals: 6.38 per 10,000 patient-days (range: 3.25-12.05) and 4.18 per 1,000 admissions (range: 1.92-8.59) in 11 tertiary hospitals, vs. 9.45 per 10,000 patient-days (range: 5.68-13.90) and 6.73 per 1,000 admissions (range: 3.18-15.85) in seven general hospitals. With regard to HIRA data, the incidence of CDI in all hospitals has been increasing over the 13-year-period: from 0.3 to 1.8 per 10,000 patient-days, 0.3 to 1.6 per 1,000 admissions, and 6.9 to 56.9 per 100,000 population, respectively. CONCLUSION: The incidence of CDI in Korea has been gradually increasing, and its recent value is as high as that in the United State and Europe. CDI is underestimated, particularly in general hospitals in Korea.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Infecção Hospitalar , Humanos , Estudos Prospectivos , Incidência , Conduta Expectante , Infecção Hospitalar/epidemiologia , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/epidemiologia , República da Coreia/epidemiologia , Centros de Atenção Terciária , Seguro Saúde
5.
Emerg Infect Dis ; 29(5): 997-1001, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36856759

RESUMO

We report a case of occupational monkeypox virus infection from a needlestick injury in a healthcare worker in South Korea and review similar reports in the literature during 2022. Postexposure prophylactic treatment with a third-generation smallpox vaccine and antiviral agent tecovirimat inhibited local virus spread and alleviated lesion pain.


Assuntos
Mpox , Ferimentos Penetrantes Produzidos por Agulha , Vacina Antivariólica , Humanos , Monkeypox virus , Pessoal de Saúde , República da Coreia/epidemiologia , Mpox/diagnóstico , Mpox/epidemiologia
6.
J Med Virol ; 95(11): e29199, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37916645

RESUMO

Despite the importance of antigen-specific T cells in infectious disease, characterizing and tracking clonally amplified T cells during the progression of a patient's symptoms remain unclear. Here, we performed a longitudinal, in-depth single-cell multiomics analysis of samples from asymptomatic, mild, usual severe, and delayed severe patients of SARS-CoV-2 infection. Our in-depth analysis revealed that hyperactive or improper T-cell responses were more aggressive in delayed severe patients. Interestingly, tracking of antigen-specific T-cell receptor (TCR) clonotypes along the developmental trajectory indicated an attenuation in functional T cells upon severity. In addition, increased glycolysis and interleukin-6 signaling in the cytotoxic T cells were markedly distinct in delayed severe patients compared to usual severe patients, particularly in the middle and late stages of infection. Tracking B-cell receptor clonotypes also revealed distinct transitions and somatic hypermutations within B cells across different levels of disease severity. Our results suggest that single-cell TCR clonotype tracking can distinguish the severity of patients through immunological hallmarks, leading to a better understanding of the severity differences in and improving the management of infectious diseases by analyzing the dynamics of immune responses over time.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T Citotóxicos , Linfócitos B
7.
J Med Virol ; 95(12): e29329, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38140877

RESUMO

Developing new antibody assays for emerging SARS-CoV-2 variants is challenging. SARS-CoV-2 surrogate virus neutralization tests (sVNT) targeting Omicron BA.1 and BA.5 have been devised, but their performance needs to be validated in comparison with quantitative immunoassays. First, using 1749 PRNT-positive sera, we noticed that log-transformed optical density (OD) ratio of wild-type (WT) sVNT exhibited better titer-correlation with plaque reduction neutralization test (PRNT) than % inhibition value. Second, we tried 798 dilutional titration tests with 103 sera, but nonlinear correlation between OD ratio and antibody concentration limited titration of sVNT. Third, the titer-correlations of two sVNT kits for BA.1 and two quantitative immunoassays for WT were evaluated with BA.1 and BA.5 PRNT. All tested kits exhibited a linear correlation with PRNT titers, but the sVNT kits exhibited high false-negative rates (cPass-BA.1 kit, 45.4% for BA.1 and 44.2% for BA.5; STANDARD F-BA.1 kit, 1.9% for BA.1 and 2.2% for BA.5), while quantitative immunoassays showed 100% sensitivity. Linear mixed-effects model suggested superior titer-correlation with PRNT for quantitative immunoassays compared to sVNT kits. Taken together, the use of quantitative immunoassays for WT, rather than rapid development of new kits, would be practical for predicting neutralizing activities against emerging new variants.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Testes de Neutralização , SARS-CoV-2/genética , COVID-19/diagnóstico , Imunoensaio , Anticorpos Neutralizantes , Anticorpos Antivirais
8.
Int Microbiol ; 26(3): 563-577, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36646920

RESUMO

BACKGROUND: Concerns regarding antimicrobial resistance (AMR) have resulted in the World Health Organization (WHO) designating so-called global priority pathogens (GPPs). However, little discussion has focused on the diagnosis of GPPs. To enable the simultaneous identification of pathogens and AMR, we developed a modular real-time nucleic acid amplification test (MRT-NAAT). METHODS: Sequence-specific primers for each modular unit for MRT-NAAT pathogen identification and AMR sets were designed. The composition of the reaction mixture and the real-time PCR program were unified irrespective of primer type so to give MRT-NAAT modularity. Standard strains and clinical isolates were used to evaluate the performance of MRT-NAAT by real-time PCR and melting curve analysis. Probit analysis for the MRT-NAAT pathogen identification set was used to assess the limit of detection (LoD). RESULTS: The MRT-NAAT pathogen identification set was made up of 15 modular units 109-199 bp in product size and with a Tms of 75.5-87.5 °C. The LoD was < 15.548 fg/µL, and nine modular units successfully detected the target pathogens. The MRT-NAAT AMR set included 24 modular units 65-785 bp in product size with a Tms of 75.5-87.5 °C; it showed high performance for detecting GPP target genes and variants. CONCLUSIONS: MRT-NAAT enables pathogen identification and AMR gene detection and is time-effective. By unifying the reaction settings of each modular unit, the modularity where combinations of primers can be used according to need could be achieved. This would greatly help in reflecting the researcher's need and the AMR status of a certain region while successfully detecting pathogens and AMR genes.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Organização Mundial da Saúde , Testes Diagnósticos de Rotina
9.
Vascular ; 31(6): 1230-1239, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35762344

RESUMO

OBJECTIVES: To explore the etiology of May-Thurner syndrome (MTS) with acute iliofemoral deep vein thrombosis (DVT) regarding imaging findings and clinical features. METHODS: We retrospectively analyzed 57 patients with acute left iliofemoral DVT from 2015 to 2020. The diameter of left common iliac vein (LCIV) at the maximal compression site and its percent compression regarding the average diameter of the uncompressed iliac vein were recorded in central and distal portions of the LCIV according to the location in the quadrant of lumbar vertebral body. Compression was categorized into simple and bony MTS; Simple MTS as LCIV compressed by the right common iliac artery (RCIA) versus Bony MTS as LCIV by lower lumbar degenerative changes regardless of RCIA compression. Initial computed tomographic venography (CTV) regarding chronic change of LCIV such as fibrotic atrophy or cordlike obliteration, extent of thrombus, and lumbar degenerative changes were evaluated. Therapeutic effect after initial therapy was assessed in follow-up CTVs after 3-6 months. RESULTS: All patients showed LCIV compression with 19 simple MTS (mean age, 42.8 ± 14.1 years [23-67 years]; 12 females; symptom for 4.4 ± 5.5 days) and 38 bony MTS (mean age, 73.0 ± 10.2 years [49-85 years]; 26 females; symptom for 5.5 ± 4.8 days). There was significant difference in age (p < .001) and no significant difference in sex or symptom duration between two groups (p = .691 and 0.415, respectively). All simple MTS showed compression only in the central LCIV and half of bony MTS showed compression in both central and distal LCIV (p < .001). Among the lumbar degenerative changes, symmetric anterolateral osteophyte (p < .001) and asymmetric osteophyte (p < .001) were significantly associated with bony MTS, but not scoliosis (p = .799), compared to simple MTS. Although there was no significant difference in chronic change of LCIV, thrombosis extent, and therapeutic effect between two groups (p > .05), chronic change of LCIV showed significant difference between single and dual compression (23.7% vs. 57.9%, p = .024) and residual thrombus after initial therapy was occurred in 21.1% of single compression and 47.4% in dual compression with non-significant trend (p = .082). CONCLUSION: Bony MTS related to lumbar degenerative changes with acute iliofemoral DVT occurs in older patients, presenting more than one stenosis at LCIV, inducing more chronic change with possibly weaker therapeutic effect than simple MTS.


Assuntos
Síndrome de May-Thurner , Osteófito , Trombose , Trombose Venosa , Feminino , Humanos , Idoso , Adulto , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Síndrome de May-Thurner/diagnóstico por imagem , Síndrome de May-Thurner/terapia , Síndrome de May-Thurner/complicações , Estudos Retrospectivos , Flebografia/efeitos adversos , Osteófito/complicações , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/terapia , Trombose Venosa/complicações , Tomografia Computadorizada por Raios X/efeitos adversos , Veia Ilíaca/diagnóstico por imagem
10.
J Korean Med Sci ; 38(25): e189, 2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37365725

RESUMO

BACKGROUND: Although coronavirus disease 2019 (COVID-19) is a viral infection, antibiotics are often prescribed due to concerns about accompanying bacterial infection. Therefore, we aimed to analyze the number of patients with COVID-19 who received antibiotic prescriptions, as well as factors that influenced antibiotics prescription, using the National Health Insurance System database. METHODS: We retrospectively reviewed claims data for adults aged ≥ 19 years hospitalized for COVID-19 from December 1, 2019 to December 31, 2020. According to the National Institutes of Health guidelines for severity classification, we calculated the proportion of patients who received antibiotics and the number of days of therapy per 1,000 patient-days. Factors contributing to antibiotic use were determined using linear regression analysis. In addition, antibiotic prescription data for patients with influenza hospitalized from 2018 to 2021 were compared with those for patients with COVID-19, using an integrated database from Korea Disease Control and Prevention Agency-COVID19-National Health Insurance Service cohort (K-COV-N cohort), which was partially adjusted and obtained from October 2020 to December 2021. RESULTS: Of the 55,228 patients, 46.6% were males, 55.9% were aged ≥ 50 years, and most patients (88.7%) had no underlying diseases. The majority (84.3%; n = 46,576) were classified as having mild-to-moderate illness, with 11.2% (n = 6,168) and 4.5% (n = 2,484) having severe and critical illness, respectively. Antibiotics were prescribed to 27.3% (n = 15,081) of the total study population, and to 73.8%, 87.6%, and 17.9% of patients with severe, critical, and mild-to-moderate illness, respectively. Fluoroquinolones were the most commonly prescribed antibiotics (15.1%; n = 8,348), followed by third-generation cephalosporins (10.4%; n = 5,729) and beta-lactam/beta-lactamase inhibitors (6.9%; n = 3,822). Older age, COVID-19 severity, and underlying medical conditions contributed significantly to antibiotic prescription requirement. The antibiotic use rate was higher in the influenza group (57.1%) than in the total COVID-19 patient group (21.2%), and higher in severe-to-critical COVID-19 cases (66.6%) than in influenza cases. CONCLUSION: Although most patients with COVID-19 had mild to moderate illness, more than a quarter were prescribed antibiotics. Judicious use of antibiotics is necessary for patients with COVID-19, considering the severity of disease and risk of bacterial co-infection.


Assuntos
Infecções Bacterianas , COVID-19 , Influenza Humana , Adulto , Masculino , Humanos , Feminino , Antibacterianos/uso terapêutico , Influenza Humana/tratamento farmacológico , Estudos Retrospectivos , Infecções Bacterianas/tratamento farmacológico , Prescrições de Medicamentos , República da Coreia/epidemiologia , Programas Nacionais de Saúde
11.
J Korean Med Sci ; 38(16): e129, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37096312

RESUMO

BACKGROUND: Alpha-toxin (AT), a major virulence factor of Staphylococcus aureus, is an important immunotherapeutic target to prevent or treat invasive S. aureus infections. Previous studies have suggested that anti-AT antibodies (Abs) may have a protective role against S. aureus bacteremia (SAB), but their function remains unclear. Therefore, we aimed to investigate the association between serum anti-AT Ab levels and clinical outcomes of SAB. METHODS: Patients from a prospective SAB cohort at a tertiary-care medical center (n = 51) were enrolled in the study from July 2016 to January 2019. Patients without symptoms or signs of infection were enrolled as controls (n = 100). Blood samples were collected before the onset of SAB and at 2- and 4-weeks post-bacteremia. Anti-AT immunoglobin G (IgG) levels were measured using an enzyme-linked immunosorbent assay. All clinical S. aureus isolates were tested for the presence of hla using polymerase chain reaction. RESULTS: Anti-AT IgG levels in patients with SAB before the onset of bacteremia did not differ significantly from those in non-infectious controls. Pre-bacteremic anti-AT IgG levels tended to be lower in patients with worse clinical outcomes (7-day mortality, persistent bacteremia, metastatic infection, septic shock), although the differences were not statistically significant. Patients who needed intensive care unit care had significantly lower anti-AT IgG levels at 2 weeks post-bacteremia (P = 0.020). CONCLUSION: The study findings suggest that lower anti-AT Ab responses before and during SAB, reflective of immune dysfunction, are associated with more severe clinical presentations of infection.


Assuntos
Bacteriemia , Infecções Estafilocócicas , Humanos , Staphylococcus aureus , Estudos Prospectivos , Formação de Anticorpos , Bacteriemia/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Imunoglobulina G , Antibacterianos/uso terapêutico
12.
J Korean Med Sci ; 38(14): e101, 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37038640

RESUMO

The current guidelines for therapeutic drug monitoring (TDM) of vancomycin suggest a target 24-hour area under the curve (AUC0-24) of 400 to 600 mg*h/L for serious methicillin-resistant Staphylococcus aureus infections. In this study, the predictabilities of acute kidney injury (AKI) of various TDM target parameters, target levels, and sampling methods were evaluated in patients who underwent TDM from January 2020 to December 2020. The AUC0-24 and trough values were calculated by both one- and two-point sampling methods, and were evaluated for the predictability of AKI. Among the AUC0-24 cutoff comparisons, the threshold value of 500 mg*h/L in the two sampling methods was statistically significant (P = 0.042) when evaluated for the predictability of AKI. Analysis by an receiver operating characteristic curve estimated an AUC0-24 cutoff value of 563.45 mg*h/L as a predictor of AKI, and was proposed as the upper limit of TDM target.


Assuntos
Injúria Renal Aguda , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Vancomicina/uso terapêutico , Antibacterianos/uso terapêutico , Monitoramento de Medicamentos/métodos , Estudos Retrospectivos , Área Sob a Curva , Rim , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/prevenção & controle , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/prevenção & controle
13.
Korean J Physiol Pharmacol ; 27(1): 113-125, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36575939

RESUMO

It has been reported that stressful events in early life influence behavior in adulthood and are associated with different psychiatric disorders, such as major depression, post-traumatic stress disorder, bipolar disorder, and anxiety disorder. Maternal separation (MS) is a representative animal model for reproducing childhood stress. It is used as an animal model for depression, and has well-known effects, such as increasing anxiety behavior and causing abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis. This study investigated the effect of MS on anxiety or aggression-like behavior and the number of GABAergic neurons in the hippocampus. Mice were separated from their dams for four hours per day for 19 d from postnatal day two. Elevated plus maze (EPM) test, resident-intruder (RI) test, and counted glutamic acid decarboxylase 67 (GAD67) or parvalbumin (PV) positive cells in the hippocampus were executed using immunohistochemistry. The maternal segregation group exhibited increased anxiety and aggression in the EPM test and the RI test. GAD67-positive neurons were increased in the hippocampal regions we observed: dentate gyrus (DG), CA3, CA1, subiculum, presubiculum, and parasubiculum. PV-positive neurons were increased in the DG, CA3, presubiculum, and parasubiculum. Consistent with behavioral changes, corticosterone was increased in the MS group, suggesting that the behavioral changes induced by MS were expressed through the effect on the HPA axis. Altogether, MS alters anxiety and aggression levels, possibly through alteration of cytoarchitecture and output of the ventral hippocampus that induces the dysfunction of the HPA axis.

14.
J Anat ; 241(6): 1477-1488, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36073345

RESUMO

Although the level of neuroscience research is rapidly developing with the introduction of new technologies, the method of neuroanatomy education remains at the traditional level and requires improvement to meet the needs of educators and trainees. We developed a new three-dimensional (3D) printed device (human brain-cutting mold, HBCM) for creating human brain slices; moreover, we demonstrated a simple method for creating semi-permanent ultraviolet (UV) resin-mounted brain slice specimens for neuroanatomy education. We obtained brain slices of uniform thickness (3 mm) through the HBCM; the resultant brain slices were optimal for assessing morphological details of the human brain. Furthermore, we used an agar-embedding method for brain-slicing with the HBCM, which minimized geometrical distortions of the brain slices. Also, we prepared semi-permanent brain serial specimens using an acrylic brain slice frame and UV-curable resin, which was highly compatible with moist bio-specimens. During UV resin curing, neither air bubble formation nor color change occurred. The resultant UV resin-mounted brain slices produced definite coronal sections with high transparency and morphological accuracy. We also performed 3D modeling by stacking brain slice images that differentiated the cortical area and nine subcortical regions via manual segmentation. This method could be a reliable alternative for displaying high-quality human brain slices and would be helpful for students and trainee to understand anatomical orientation from 2D images to 3D structures. Also, this may present an innovative approach for preparing and preserving coronal sections of the normal or pathological human brain.


Assuntos
Encéfalo , Neuroanatomia , Humanos , Encéfalo/anatomia & histologia , Imageamento Tridimensional
15.
Eur J Clin Microbiol Infect Dis ; 41(12): 1407-1413, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36207553

RESUMO

Invasive group B Streptococcus (GBS) infections are increasing among adults with underlying health conditions; however, clinical manifestations and serotype distribution remain unclear. This study investigated the molecular characteristics and antimicrobial resistance of invasive GBS in Korean adults. GBS isolates from patients with invasive diseases during 2006-2015 were investigated for capsular serotype, multilocus sequence type (ST), antimicrobial susceptibility, and resistance genes. Among the 74 isolates analyzed, the most common serotype was Ib (31.1%), followed by III (21.6%), V (20.3%), Ia (12.2%), and VI (12.2%). Thirteen STs were detected, with ST1, ST10, ST19, and ST23 as the most prevalent. The dominant capsular serotype exhibited by ST1 was V, and those expressed by ST10, ST19, and ST23 were Ib, III, and Ia, respectively. Erythromycin and levofloxacin resistance were observed in 33.8% and 31.1% of the isolates, respectively. ST10-Ib (n = 11/11, 100%) and ST654-Ib (n = 3/3, 100%) were dominant levofloxacin-resistant strains. Serotypes Ib, III, and V were most common among adults, which is inconsistent with recent reports in Korea where III, V, and Ia were predominant in infants. The difference in the serotype distribution between adults and children may be associated with the selective pressure imparted by antibiotics.


Assuntos
Levofloxacino , Infecções Estreptocócicas , Lactente , Adulto , Criança , Humanos , Epidemiologia Molecular , Tipagem de Sequências Multilocus , Streptococcus agalactiae , Infecções Estreptocócicas/microbiologia , Sorogrupo , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Encaminhamento e Consulta , Farmacorresistência Bacteriana , Sorotipagem
16.
Eur J Clin Microbiol Infect Dis ; 41(12): 1459-1465, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36227508

RESUMO

This retrospective study aimed to clarify the interspecies differences in the clinical characteristics and risk factors of bloodstream infection (BSI) due to third-generation cephalosporin-resistant (3GC-R) Escherichia coli (EC) and Klebsiella pneumoniae (KP) in patients with liver cirrhosis (LC). KP BSI had more comorbidities and higher treatment failure rate than EC BSI. Non-alcoholic LC was a risk factor for treatment failure in EC, whereas it was not associated with KP. Risk factors for BSI due to 3GC-R strain were nosocomial infection in EC, and ß-lactam/fluoroquinolone treatment ≤ 30 days in KP. These results could help predict outcomes of BSI and improve clinical practice.


Assuntos
Bacteriemia , Infecções por Escherichia coli , Infecções por Klebsiella , Sepse , Humanos , Klebsiella pneumoniae , Escherichia coli , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Resistência às Cefalosporinas , Estudos Retrospectivos , Bacteriemia/tratamento farmacológico , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/epidemiologia , Fatores de Risco , Sepse/tratamento farmacológico , Cirrose Hepática/complicações , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
17.
J Pediatr Hematol Oncol ; 44(3): e713-e718, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35319510

RESUMO

PURPOSE: Extramedullary infiltration (EMI) is a rare condition defined by the accumulation of myeloid tumor cells beyond the bone marrow. The clinical significance is still controversial. This study was aimed to evaluate the incidence, characteristics, and prognostic significance of EMI on complete magnetic resonance imaging (MRI) investigation in newly diagnosed pediatric acute myeloid leukemia (AML) patients who are asymptomatic without clinical evidence to suspect EMI. MATERIALS AND METHODS: Retrospective clinical and radiologic review of 121 patients with MRI examination at the time of initial diagnosis of AML without any clinical evidence suggestive of EMI was performed. Patients were divided into 2 groups according to the presence or absence of EMI, and the relationship between EMI and established risk factors was analyzed. Initial white blood cell count, the occurrence of an event (including relapse, death, and primary refractory disease), survival status, and detailed information on cytogenetic/molecular status was performed by a thorough review of electronic medical records system. All patients underwent full imaging evaluation with the contrast-enhanced whole body and some regional MRI at the time of initial diagnosis. RESULTS: The median age at diagnosis was 10.77 years (range, 0.37 to 18.83 y). Based on the risk stratification system of AML, 36, 45, and 40 patients are classified as low-risk, intermediate-risk, and high-risk groups, respectively. MRI at the time of the initial diagnosis of AML revealed 35 of 121 patients (28.9%) with EMI. The most common site of EMI was a skull, followed by the lower extremity bone and meninges of the brain. The median age at diagnosis was significantly younger in patients with EMI (7.87 vs. 11.08 y, P=0.0212). Low incidence of FLT3/ITD mutation, low incidence of AML-ETO gene rearrangement, and the larger extent and more severe degree of bone marrow involvement was related with EMI. However, there was no significant prognostic difference in event-free survival and overall survival regardless of the presence of EMI in the overall patient population and each risk group. The location of EMI occurrence was also not related to prognosis. CONCLUSIONS: Even if EMI symptoms are not evident, surveillance MRI scans at the initial diagnosis of pediatric AML patients are very helpful in detecting a significant number of EMIs. Younger age, some molecular features, and more severe bone marrow involvement of AML patients were related with EMI. However, there was no significant prognostic difference between patients with or without EMI regardless of risk group. Further prospective investigation is necessary to validate the prognostic effect of EMI in a larger group of patients with different risk groups.


Assuntos
Leucemia Mieloide Aguda , Imageamento por Ressonância Magnética , Criança , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Prognóstico , Estudos Retrospectivos , Fatores de Risco
18.
J Korean Med Sci ; 37(32): e252, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35971766

RESUMO

BACKGROUND: The clinical features of coronavirus disease 2019 (COVID-19) patients in the COVID-19 vaccination era need to be clarified because breakthrough infection after vaccination is not uncommon. METHODS: We retrospectively analyzed hospitalized COVID-19 patients during a delta variant-dominant period 6 months after the national COVID-19 vaccination rollout. The clinical characteristics and risk factors for severe progression were assessed and subclassified according to vaccination status. RESULTS: A total of 438 COVID-19 patients were included; the numbers of patients in the unvaccinated, partially vaccinated and fully vaccinated groups were 188 (42.9%), 117 (26.7%) and 133 (30.4%), respectively. The vaccinated group was older, less symptomatic and had a higher Charlson comorbidity index at presentation. The proportions of patients who experienced severe progression in the unvaccinated and fully vaccinated groups were 20.3% (31/153) and 10.8% (13/120), respectively. Older age, diabetes mellitus, solid cancer, elevated levels of lactate dehydrogenase and chest X-ray abnormalities were associated with severe progression, and the vaccination at least once was the only protective factor for severe progression. Chest X-ray abnormalities at presentation were the only predictor for severe progression among fully vaccinated patients. CONCLUSION: In the hospitalized setting, vaccinated and unvaccinated COVID-19 patients showed different clinical features and risk of oxygen demand despite a relatively high proportion of patients in the two groups. Vaccination needs to be assessed as an initial checkpoint, and chest X-ray may be helpful for predicting severe progression in vaccinated patients.


Assuntos
Vacinas contra COVID-19 , COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Humanos , Estudos Retrospectivos , SARS-CoV-2 , Vacinação
19.
J Korean Med Sci ; 37(16): e126, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35470600

RESUMO

BACKGROUND: The relationship between changes in anxiety levels and personal protective equipment (PPE) use is yet to be evaluated. The present study assessed this relationship among healthcare workers (HCWs) involved in the care of patients with coronavirus disease 2019 (COVID-19). METHODS: An online survey was conducted in a municipal hospital with 195 nationally designated negative pressure isolation units in Korea. Anxiety level was measured using the self-rating anxiety scale (SAS), and changes in anxiety levels were assessed based on the time when COVID-19 vaccine was introduced in March 2021 in Korea. Monthly PPE usage between June 2020 and May 2021 was investigated. RESULTS: The mean SAS score (33.25 ± 5.97) was within normal range and was lower than those reported in previous studies conducted before COVID-19 vaccination became available. Among the 93 HCWs who participated, 64 (68.8%) answered that their fear of contracting COVID-19 decreased after vaccination. The number of coveralls used per patient decreased from 33.6 to 0. However, a demand for more PPE than necessary was observed in situations where HCWs were exposed to body fluids and secretions (n = 38, 40.9%). Excessive demand for PPE was not related to age, working experience, or SAS score. CONCLUSION: Anxiety in HCWs exposed to COVID-19 was lower than it was during the early period of the pandemic, and the period before vaccination was introduced. The number of coveralls used per patient also decreased although an excessive demand for PPE was observed.


Assuntos
COVID-19 , Equipamento de Proteção Individual , Ansiedade/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Pessoal de Saúde , Humanos , SARS-CoV-2
20.
J Korean Med Sci ; 37(34): e262, 2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36038958

RESUMO

BACKGROUND: This study aimed to investigate the effects of comprehensive rehabilitation management on functional recovery and examine the correlation between clinical parameters and improvements in functional outcomes in severe-to-critical inpatients with coronavirus disease 2019 (COVID-19) in a tertiary hospital. METHODS: Post-acute COVID-19 patients who had a World Health Organization (WHO) ordinal scale of 5-7, underwent intensive care, and received comprehensive rehabilitation management, including exercise programs, nutritional support, dysphagia evaluation, and psychological care were included. The appendicular skeletal muscle mass index (SMI), Medical Research Council sum score, handgrip strength, number of repetitions in the 1-minute sit-to-stand test, gait speed, Berg Balance Scale (BBS), and Functional Ambulation Classification (FAC) were evaluated at hospital stay, discharge, and 1-month follow-up. The correlation between the rehabilitation dose and improvement in each outcome measure was analyzed. RESULTS: Overall, 37 patients were enrolled, of whom 59.5% and 32.4% had a score of 6 and 7 on the WHO ordinal scale, respectively. Lengths of stay in the intensive care unit and hospital were 33.6 ± 23.9 and 63.8 ± 36.5 days. Outcome measures revealed significant improvements at discharge and 1-month follow-up. The SMI was significantly increased at the 1-month follow-up (6.13 [5.24-7.76]) compared with that during the hospital stay (5.80 [5.39-7.05]). We identified dose-response associations between the rehabilitation dose and FAC (ρ = 0.46) and BBS (ρ = 0.50) scores. Patients with older age, longer hospitalization, longer stay at the intensive care unit, longer duration of mechanical ventilation, tracheostomy, a more depressive mood, and poorer nutritional status revealed poorer improvement in gait speed at the 1-month follow-up. CONCLUSION: Comprehensive rehabilitation management effectively improved muscle mass, muscle strength, and physical performance in severe-to-critical COVID-19 patients. Dose-response relationship of rehabilitation and functional improvement emphasizes the importance of intensive post-acute inpatient rehabilitation in COVID-19 survivors. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05104411.


Assuntos
COVID-19 , Estudos de Coortes , Força da Mão , Humanos , Pacientes Internados , Unidades de Terapia Intensiva , Centros de Atenção Terciária
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