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1.
Cell Host Microbe ; 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39059396

ABSTRACT

The gut microbiome significantly influences immune responses and the efficacy of immune checkpoint inhibitors. We conducted a clinical trial (NCT04264975) combining an anti-programmed death-1 (PD-1) inhibitor with fecal microbiota transplantation (FMT) from anti-PD-1 responder in 13 patients with anti-PD-1-refractory advanced solid cancers. FMT induced sustained microbiota changes and clinical benefits in 6 of 13 patients, with 1 partial response and 5 stable diseases, achieving an objective response rate of 7.7% and a disease control rate of 46.2%. The clinical response correlates with increased cytotoxic T cells and immune cytokines in blood and tumors. We isolated Prevotella merdae Immunoactis from a responder to FMT, which stimulates T cell activity and suppresses tumor growth in mice by enhancing cytotoxic T cell infiltration. Additionally, we found Lactobacillus salivarius and Bacteroides plebeius may inhibit anti-tumor immunity. Our findings suggest that FMT with beneficial microbiota can overcome resistance to anti-PD-1 inhibitors in advanced solid cancers, especially gastrointestinal cancers.

2.
Sci Rep ; 14(1): 15472, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38969796

ABSTRACT

This study evaluated the determinants of mortality and the T cell immune response in patients with persistent Staphylococcus aureus bacteremia (SAB). This was a prospective cohort study and patients with confirmed SAB were enrolled from 2008 to 2020. We compared clinical, microbiological, and genotypic features between surviving and deceased patients with persistent SAB. The concentrations of cytokines and the proportions of IFN-γ secreting CD4+ T cells were measured serially during the bacteremia period. Of the 1760 patients, 242 had persistent bacteremia (PB), and 49 PB patients died within 30 days. In the multivariate analysis, the APACHE II score and female sex were independently associated with 30 days mortality. The level of IL-10 was significantly increased in the plasma of patients with a high Pitt bacteremia score and those who died within 12 weeks from the index day. The proportion of IFN-γ-secreting CD4+ T cells were the highest just before the positive-to-negative conversion of blood cultures in patients with a low Pitt bacteremia score and those who survived for 12 weeks. The level of IL-10 is correlated with clinical outcomes in PB patients. IFN-γ secreting CD4+ T cells might play a pivotal role in SAB PB.


Subject(s)
Bacteremia , CD4-Positive T-Lymphocytes , Staphylococcal Infections , Staphylococcus aureus , Humans , Male , Female , Bacteremia/mortality , Bacteremia/microbiology , Bacteremia/immunology , CD4-Positive T-Lymphocytes/immunology , Staphylococcal Infections/mortality , Staphylococcal Infections/immunology , Staphylococcal Infections/microbiology , Staphylococcus aureus/immunology , Middle Aged , Risk Factors , Aged , Prospective Studies , Interferon-gamma/blood , Interferon-gamma/metabolism , Interleukin-10/blood , Adult , Cytokines/blood , Cytokines/metabolism
3.
J Korean Med Sci ; 39(25): e208, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38952349

ABSTRACT

A 30-year-old Korean man with myelodysplastic syndrome admitted hospital due to undifferentiated fever and recurrent skin lesions. He received combination therapy with high doses of meropenem, tigecycline and amikacin, yielding carbapenem resistant Klebsiella pneumoniae (CRKP) harboring K. pneumoniae carbapenemase (KPC)-2 from blood cultures on hospital day (HD) 23. Ceftazidime/avibactam was started at HD 37 and CRKP was eradicated from blood cultures after 5 days. However, ceftazidime/avibactam-resistant CRKP carrying KPC-44 emerged after 26 days of ceftazidime/avibactam treatment and then ceftazidime/avibactam-resistant, carbapenem-susceptible K. pneumoniae carrying KPC-135 was isolated on HD 65. The 3-D homology of KPC protein showed that hot spot changes in the omega loop could be attributed to ceftazidime/avibactam resistance and loss of carbapenem resistance. Whole genome sequencing of serial isolates supported that phenotypic variation was due to clonal evolution than clonal replacement. The treatment regimen was changed from CAZ/AVI to meropenem-based therapy (meropenem 1 g iv q 8 hours and amikacin 600 mg iv per day) starting with HD 72. CAZ/AVI-susceptible CRKP was presented again from blood cultures on HD 84, and the patient expired on HD 85. This is the first Korean report on the acquisition of ceftazidime/avibactam resistance through the emergence of blaKPC variants.


Subject(s)
Anti-Bacterial Agents , Azabicyclo Compounds , Bacteremia , Ceftazidime , Drug Combinations , Klebsiella Infections , Klebsiella pneumoniae , Microbial Sensitivity Tests , beta-Lactamases , Humans , Ceftazidime/therapeutic use , Ceftazidime/pharmacology , Klebsiella pneumoniae/isolation & purification , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/drug effects , Male , Azabicyclo Compounds/therapeutic use , Adult , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacology , beta-Lactamases/genetics , beta-Lactamases/metabolism , Klebsiella Infections/drug therapy , Klebsiella Infections/microbiology , Bacteremia/drug therapy , Bacteremia/microbiology , Carbapenems/therapeutic use , Carbapenems/pharmacology , Whole Genome Sequencing , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Meropenem/therapeutic use , Meropenem/pharmacology , Drug Resistance, Multiple, Bacterial/genetics
4.
Vaccines (Basel) ; 12(7)2024 Jul 08.
Article in English | MEDLINE | ID: mdl-39066390

ABSTRACT

Background: We aimed to identify the risk factors for impaired cellular and humoral immunity after three doses of the SARS-CoV-2 vaccine. Methods: Six months after the third vaccine dose, T-cell immunity was evaluated using interferon-gamma release assays (IGRAs) in 60 healthy and 139 immunocompromised (IC) individuals, including patients with hematologic malignancy (HM), solid malignancy (SM), rheumatic disease (RD), and kidney transplantation (KT). Neutralizing antibody titers were measured using the plaque reduction neutralization test (PRNT) and surrogate virus neutralization test (sVNT). Results: T-cell immunity results showed that the percentages of IGRA-positive results using wild-type/alpha spike protein (SP) and beta/gamma SP were 85% (51/60) and 75% (45/60), respectively, in healthy individuals and 45.6% (62/136) and 40.4% (55/136), respectively, in IC individuals. IC with SM or KT showed a high percentage of IGRA-negative results. The underlying disease poses a risk for impaired cellular immune response to wild-type SP. The risk was low when all doses were administered as mRNA vaccines. The risk factors for an impaired cellular immune response to beta/gamma SP were underlying disease and monocyte%. In the sVNT using wild-type SP, 12 of 191 (6.3%) individuals tested negative. In the PRNT of 46 random samples, 6 (13%) individuals tested negative for the wild-type virus, and 19 (41.3%) tested negative with omicrons. KT poses a risk for an impaired humoral immune response. Conclusions: Underlying disease poses a risk for impaired cellular immune response after the third dose of the SARS-CoV-2 vaccine; KT poses a risk for impaired humoral immune response, emphasizing the requirement of precautions in patients.

5.
J Korean Med Sci ; 39(28): e224, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39048304

ABSTRACT

The seropositivity of measles antibodies among 261 autologous stem cell transplant recipients (ASCTs) in Korea, assessed approximately 1-2 years after transplant (median, 11 months; interquartile range, 9-14), was significantly lower than age- and sex-matched control healthcare workers (83.1% [217/261] vs. 90.3% [539/597], P = 0.002). The findings underscore the vulnerability of adult ASCT recipients to measles. Clinicians should prioritize testing for measles IgG after ASCT and consider vaccination for ASCT recipients who remain seronegative 2 years after ASCT.


Subject(s)
Antibodies, Viral , Hematopoietic Stem Cell Transplantation , Immunoglobulin G , Measles , Transplantation, Autologous , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Measles/immunology , Measles/prevention & control , Republic of Korea , Male , Female , Adult , Antibodies, Viral/blood , Middle Aged , Immunoglobulin G/blood , Measles Vaccine/immunology , Measles virus/immunology
6.
Microbiol Spectr ; : e0033324, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38916352

ABSTRACT

The incidence of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) infection is increasing and is associated with vancomycin treatment failures. However, studies investigating the risk factors for treatment failure in hVISA infection are limited. Patients with hVISA bacteremia treated with vancomycin over 7 days between August 2008 and June 2020 were enrolled in this study. Clinical and microbiological characteristics were compared between vancomycin treatment failure and success groups to identify the risk factors for vancomycin treatment failure. Among the 180 patients with hVISA bacteremia, 102 patients treated with vancomycin over 7 days were included. Vancomycin treatment failed in 80 (78%) patients. Patients in the vancomycin treatment failure group were older (P < 0.001) and more frequently had solid cancer (P = 0.04) than those in the vancomycin treatment success group. Solid organ transplantation (SOT) was more frequent (P < 0.001) in the vancomycin treatment success group. The Charlson comorbidity index (P = 0.01) and Acute Physiology and Chronic Health Evaluation II scores (P < 0.001) were higher in the vancomycin treatment failure group. In multivariate analysis, independent risk factors for vancomycin treatment failure were old age and severity of bacteremia. SOT and vancomycin minimal inhibitory concentration (MIC) ≤ 1.0 mg/L using the broth microdilution (BMD) method were associated with successful vancomycin treatment. Old age and infection severity were independent risk factors for vancomycin treatment failure. Vancomycin MIC using the BMD method is an important risk factor for vancomycin treatment failure, and its use should be considered in hVISA bacteremia.IMPORTANCEIn this study, we assessed the clinical and microbiological characteristics of heterogeneous vancomycin-intermediated Staphylococcus aureus (hVISA) bacteremia and identified risk factors for vancomycin treatment failure. We found that advanced age and severity of infection were independent risk factors for vancomycin treatment failure. On the other hand, solid organ transplantation and a low vancomycin minimal inhibitory concentration were associated with successful vancomycin treatment. This study highlights the importance of vancomycin minimal inhibitory concentration in hVISA bacteremia.

7.
Am J Infect Control ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38945300

ABSTRACT

BACKGROUND: The mounted UV-C lamp requires no separate space or labor for transport, but data on its effectiveness for surface disinfection are scarce. We aimed to evaluate the performance of ceiling-mounted UV-C lamps. METHODS: This study was conducted in an empty room with UV-C lamps in the biocontainment unit of a tertiary care hospital in South Korea. UV-C lamps were installed on the ceiling of the patient room, anteroom, and toilet. Each pathogen (Staphylococcus aureus, Escherichia coli, Candida krusei, Bacillus cereus, and Mycobacterium peregrinum) was inoculated on blood agar plates and placed in 20 selected places from the UV-C lamp, and irradiation was applied for 15 min. As a control group, the bacterial solution was diluted 10,000 times and UV was not applied. RESULTS: A mean ± SD of 5.95 ± 0.91 log reduction was observed with UV irradiation compared with the control. The log reduction was greatest for S. aureus [median, 7.05 (IQR, 6.49-7.26)] and least for M. peregrinum [median, 4.88 (IQR, 4.58-5.24)]. The degree of log reduction was inversely proportional to the square of the distance from the UV-C lamp (R2 = -0.12, p < 0.001). CONCLUSIONS: In this study, ceiling-mounted UV-C demonstrated effective disinfection of at least 4-log reduction of the test organisms within a 4-m distance. Mounted UV-C lighting is a considerable option for improving surface disinfection.

10.
Vaccine ; 42(19): 3953-3960, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-38729909

ABSTRACT

INTRODUCTION: The long-term impact of initial immunogenicity induced by different primary COVID-19 vaccine series remains unclear. METHODS: A prospective cohort study was conducted at 10 tertiary hospitals in Korea from March 2021 to September 2022. Immunogenicity assessments included anti-spike protein antibody (Sab), SARS-CoV-2-specific interferon-gamma releasing assay (IGRA), and multiplex cytokine assays for spike protein-stimulated plasma. Spike proteins derived from wild-type SARS-CoV-2 and alpha variant (Spike1) and beta and gamma variant (Spike2) were utilized. RESULTS: A total of 235 healthcare workers who had received a two-dose primary vaccine series of either ChAdOx1 or BNT162b2, followed by a third booster dose of BNT162b2 (166 in the ChAdOx1/ChAdOx1/BNT162b2 (CCB) group and 69 in the BNT162b2/BNT162b2/BNT162b2 (BBB) group, based on the vaccine series) were included. Following the primary vaccine series, the BBB group exhibited significantly higher increases in Sab levels, IGRA responses, and multiple cytokines (CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1ß, interleukin (IL)-1ra, IFN-γ, IL-2, IL-4, and IL-10) compared to the CCB group (all P < 0.05). One month after the third BNT162b2 booster, the CCB group showed Sab levels comparable to those of the BBB group, and both groups exhibited lower levels after six months without breakthrough infections (BIs). However, among those who experienced BA.1/2 BIs after the third booster, Sab levels increased significantly more in the BBB group than in the CCB group (P < 0.001). IGRA responses to both Spike1 and Spike2 proteins were significantly stronger in the BBB group than the CCB group after the third booster, while only the Spike2 response were higher after BIs (P = 0.007). The BBB group exhibited stronger enhancement of T-cell cytokines (IL-2, IL-4, and IL-17A) after BIs than in the CCB group (P < 0.05). CONCLUSION: Differences in immunogenicity induced by the two primary vaccine series persisted, modulated by subsequent booster vaccinations and BIs.


Subject(s)
Antibodies, Viral , BNT162 Vaccine , COVID-19 Vaccines , COVID-19 , Immunization, Secondary , SARS-CoV-2 , Humans , Male , Female , Prospective Studies , BNT162 Vaccine/immunology , BNT162 Vaccine/administration & dosage , Adult , SARS-CoV-2/immunology , Middle Aged , COVID-19/prevention & control , COVID-19/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Immunogenicity, Vaccine , Spike Glycoprotein, Coronavirus/immunology , Cytokines/blood , Republic of Korea , ChAdOx1 nCoV-19/immunology , Health Personnel , Vaccination/methods , Breakthrough Infections
11.
Article in English | MEDLINE | ID: mdl-38697393

ABSTRACT

OBJECTIVE: The interferon-gamma releasing assay (IGRA) has been widely used to diagnose latent tuberculosis infection (TBI). However, there are limited data on the association between performance in the IGRA and risk of tuberculosis disease (TBD), as well as on the appropriate IGRA threshold for initiating TBI treatment. METHODS: The analysis was performed using the IGRA results in the Korean Military Manpower Administration database (January 2017 to December 2021), and TBD cases reported to the Korean Military Medical Command (January 2017 to June 2023). All Korean candidates for 18-month military service underwent the IGRA in the pre-enlistment examination, and enlistees who tested positive (≥0.35 IU/mL) were advised to receive TBI treatment before enlistment. RESULTS: From 2017 to 2021, 1 647 941 individuals were screened, with 29 574 testing positive for IGRA. Excluding nonenlistees namely individuals with TBD before enlistment, 19 387 individuals were IGRA positive and 1 356 324 IGRA negative. Of the positives, 4351 were excluded due to discontinued or ongoing TBI treatment at or after enlistment. During follow-up of 9219 untreated and 5818 treated positive individuals and 1 356 324 negatives, TBD occurred in 22 of the IGRA-positive individuals (97.5/100 000 person-years [95% CI, 61.1-147.7]), predominantly in the untreated group (18 cases, 130.1/100 000 person-years [95% CI, 77.1-205.7]) compared to the treated group (4 cases, 45.9/100 000 person-years [95% CI 12.5 - 117.4]), whereas 57 cases occurred in the IGRA-negative group (2.8/100 000 person-years [95% CI, 2.2-3.6]). Elevating the cutoff of IGRA from 0.35 IU/mL to 1.33 IU/mL increased positive predictive value (0.2% vs. 0.4%, p 0.03), with insignificant loss of sensitivity (24% vs. 20%, p 0.69) and decreased numbers needing treatment from 790.5 to 415.3. DISCUSSION: Elevated IGRA levels before enlistment are associated with risk of TBD during military service. It is worth considering raising the IGRA threshold for treatment of TBI in cohorts of healthy, young military individuals.

12.
Emerg Infect Dis ; 30(6): 1088-1095, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38781685

ABSTRACT

The characteristics of severe human parainfluenza virus (HPIV)-associated pneumonia in adults have not been well evaluated. We investigated epidemiologic and clinical characteristics of 143 patients with severe HPIV-associated pneumonia during 2010-2019. HPIV was the most common cause (25.2%) of severe virus-associated hospital-acquired pneumonia and the third most common cause (15.7%) of severe virus-associated community-acquired pneumonia. Hematologic malignancy (35.0%), diabetes mellitus (23.8%), and structural lung disease (21.0%) were common underlying conditions. Co-infections occurred in 54.5% of patients admitted to an intensive care unit. The 90-day mortality rate for HPIV-associated pneumonia was comparable to that for severe influenza virus-associated pneumonia (55.2% vs. 48.4%; p = 0.22). Ribavirin treatment was not associated with lower mortality rates. Fungal co-infections were associated with 82.4% of deaths. Clinicians should consider the possibility of pathogenic co-infections in patients with HPIV-associated pneumonia. Contact precautions and environmental cleaning are crucial to prevent HPIV transmission in hospital settings.


Subject(s)
Community-Acquired Infections , Tertiary Care Centers , Humans , Male , Female , Middle Aged , Community-Acquired Infections/epidemiology , Community-Acquired Infections/virology , Republic of Korea/epidemiology , Aged , Adult , Healthcare-Associated Pneumonia/epidemiology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/mortality , Coinfection/epidemiology , Paramyxoviridae Infections/epidemiology , Paramyxoviridae Infections/mortality , History, 21st Century , Cross Infection/epidemiology , Young Adult , Aged, 80 and over
13.
Sci Rep ; 14(1): 10653, 2024 05 09.
Article in English | MEDLINE | ID: mdl-38724557

ABSTRACT

The efficacy of flow diverters is influenced by the strut configuration changes resulting from size discrepancies between the stent and the parent artery. This study aimed to quantitatively analyze the impact of size discrepancies between flow diverters and parent arteries on the flow diversion effects, using computational fluid dynamics. Four silicone models with varying parent artery sizes were developed. Real flow diverters were deployed in these models to assess stent configurations at the aneurysm neck. Virtual stents were generated based on these configurations for computational fluid dynamics analysis. The changes in the reduction rate of the hemodynamic parameters were quantified to evaluate the flow diversion effect. Implanting 4.0 mm flow diverters in aneurysm models with parent artery diameters of 3.0-4.5 mm, in 0.5 mm increments, revealed that a shift from oversized to undersized flow diverters led to an increase in the reduction rates of hemodynamic parameter, accompanied by enhanced metal coverage rate and pore density. However, the flow diversion effect observed transitioning from oversizing to matching was less pronounced when moving from matching to undersizing. This emphasizes the importance of proper sizing of flow diverters, considering the benefits of undersizing and not to exceed the threshold of advantages.


Subject(s)
Hemodynamics , Stents , Humans , Models, Cardiovascular , Intracranial Aneurysm/physiopathology , Intracranial Aneurysm/surgery , Computer Simulation , Arteries/physiology , Hydrodynamics
14.
J Korean Med Sci ; 39(14): e137, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38622941

ABSTRACT

Our study analyzed 95 solid organ transplant (SOT) and 78 hematopoietic stem cell transplant (HSCT) recipients with prior coronavirus disease 2019 (COVID-19). Patients who underwent transplantation within 30 days of COVID-19 infection comprised the early group, and those who underwent transplantation post-30 days of COVID-19 infection comprised the delayed group. In the early transplantation group, no patient, whether undergoing SOT and HSCT, experienced COVID-19-associated complications. In the delayed transplantation group, one patient each from SOT and HSCT experienced COVID-19-associated complications. Additionally, among early SOT and HSCT recipients, two and six patients underwent transplantation within seven days of COVID-19 diagnosis, respectively. However, no significant differences were observed in the clinical outcomes of these patients compared to those in other patients. Early transplantation following severe acute respiratory syndrome coronavirus 2 infection can be performed without increased risk of COVID-19-associated complications. Therefore, transplantation needs not be delayed by COVID-19 infection.


Subject(s)
COVID-19 , Organ Transplantation , Humans , COVID-19 Testing , SARS-CoV-2 , Transplant Recipients
16.
Am J Cancer Res ; 14(2): 917-930, 2024.
Article in English | MEDLINE | ID: mdl-38455410

ABSTRACT

Cyclophilin B (CypB), encoded by peptidylprolyl isomerase B (PPIB), is involved in cellular transcriptional regulation, immune responses, chemotaxis, and proliferation. Recent studies have shown that PPIB/CypB is associated with tumor progression and chemoresistance in various cancers. However, the clinicopathologic significance and mechanism of action of PPIB/CypB in non-small cell lung cancer (NSCLC) remain unclear. In this study, we used RNA in situ hybridization to examine PPIB expression in 431 NSCLC tissue microarrays consisting of 295 adenocarcinomas (ADCs) and 136 squamous cell carcinomas (SCCs). Additionally, Ki-67 expression was evaluated using immunohistochemistry. The role of PPIB/CypB was assessed in five human NSCLC cell lines. There was a significant correlation between PPIB/CypB expression and Ki-67 expression in ADC (Spearman correlation r=0.374, P<0.001) and a weak correlation in SCC (r=0.229, P=0.007). In ADCs, high PPIB expression (PPIBhigh) was associated with lymph node metastasis (P=0.023), advanced disease stage (P=0.014), disease recurrence (P=0.013), and patient mortality (P=0.015). Meanwhile, high Ki-67 expression (Ki-67high) was correlated with male sex, smoking history, high pT stage, lymph node metastasis, advanced stage, disease recurrence, and patient mortality in ADC (all P<0.001). However, there was no association between either marker or clinicopathological factors, except for old age and PPIBhigh (P=0.038) in SCC. Survival analyses revealed that the combined expression of PPIBhigh/Ki-67high was an independent prognosis factor for poor disease-free survival (HR 1.424, 95% CI 1.177-1.723, P<0.001) and overall survival (HR 1.266, 95% CI 1.036-1.548, P=0.021) in ADC, but not in SCC. Furthermore, PPIB/CypB promoted the proliferation, colony formation, and migration of NSCLC cells. We also observed the oncogenic properties of PPIB/CypB expression in human bronchial epithelial cells. In conclusion, PPIB/CypB contributes to tumor growth in NSCLC, and elevated PPIB/Ki-67 levels are linked to unfavorable survival, especially in ADC.

17.
Infection ; 52(3): 1055-1061, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38347366

ABSTRACT

PURPOSE: Liver transplant (LT) recipients have an increased risk of tuberculosis (TB), which is associated with higher mortality rates. This retrospective cohort study assessed the outcome and tolerability of screening and treatment of latent tuberculosis infection (LTBI) in LT recipients. METHODS: Between March 2020 and February 2022, all adult LT candidates at our institution were screened for LTBI. The candidates who tested positive for interferon-γ-releasing assay or met epidemiological or clinical-radiological criteria for LTBI were treated and monitored. RESULTS: Among the 857 LT recipients, 199 (23.2%) were diagnosed with LTBI, of which 171 (85.9%) initiated LTBI treatment. The median duration of follow-up was 677 days. Adequate LTBI treatment occurred in 141/171 (82.5%) patients and was discontinued prematurely in 30/171 (17.5%) patients. The most common reason for discontinuation was liver enzyme elevation (11/30, 36.7%), although only five discontinued treatment due to suspicion of isoniazid-associated hepatotoxicity. None of the LTBI-treated patients developed active TB during the follow-up period, while 3.6% (1/28) of untreated LTBI patients and 0.6% (4/658) of patients without LTBI developed TB. CONCLUSION: These findings demonstrate that LTBI screening and treatment is a safe and effective strategy to prevent TB in LT recipients. However, monitoring for adverse events and liver enzyme elevation is recommended.


Subject(s)
Antitubercular Agents , Latent Tuberculosis , Liver Transplantation , Transplant Recipients , Humans , Latent Tuberculosis/drug therapy , Latent Tuberculosis/epidemiology , Liver Transplantation/adverse effects , Male , Female , Middle Aged , Retrospective Studies , Antitubercular Agents/therapeutic use , Antitubercular Agents/adverse effects , Adult , Transplant Recipients/statistics & numerical data , Treatment Outcome , Aged , Isoniazid/therapeutic use , Isoniazid/adverse effects , Cohort Studies
18.
Eur J Clin Microbiol Infect Dis ; 43(5): 841-851, 2024 May.
Article in English | MEDLINE | ID: mdl-38411778

ABSTRACT

PURPOSE: Distinguishing between complicated and uncomplicated Staphylococcus aureus bacteraemia (SAB) is therapeutically essential. However, this distinction has limitations in reflecting the heterogeneity of SAB and encouraging targeted diagnostics. Recently, a new risk stratification system for SAB metastatic infection, involving stepwise approaches to diagnosis and treatment, has been suggested. We assessed its applicability in methicillin-resistant SAB (MRSAB) patients. METHODS: We retrospectively analysed data of a 3-year multicentre, prospective cohort of hospitalised patients with MRSAB. We classified the patients into three risk groups: low, indeterminate, and high, based on the new system and compared between-group management and outcomes. RESULTS: Of 380 patients with MRSAB, 6.3% were classified as low-, 7.6% as indeterminate-, and 86.1% as high-risk for metastatic infection. No metastatic infection occurred in the low-, 6.9% in the indeterminate-, and 19.6% in the high-risk groups (P < 0.001). After an in-depth diagnostic work-up, patients were finally diagnosed as 'without metastatic infection (6.3%)', 'with metastatic infection (17.4%)', and 'uncertain for metastatic infection (76.3%)'. 30-day mortality increased as the severity of diagnosis shifted from 'without metastatic infection' to 'uncertain for metastatic infection' and 'with metastatic infection' (P = 0.09). In multivariable analysis, independent factors associated with metastatic complications were suspicion of endocarditis in transthoracic echocardiography, clinical signs of metastatic infection, Pitt bacteraemia score ≥ 4, and persistent bacteraemia. CONCLUSIONS: The new risk stratification system shows promise in predicting metastatic complications and guiding work-up and management of MRSAB. However, reducing the number of cases labelled as 'high-risk' and 'uncertain for metastatic infection' remains an area for improvement.


Subject(s)
Bacteremia , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Humans , Bacteremia/drug therapy , Bacteremia/microbiology , Bacteremia/diagnosis , Bacteremia/mortality , Staphylococcal Infections/drug therapy , Staphylococcal Infections/diagnosis , Staphylococcal Infections/microbiology , Staphylococcal Infections/mortality , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Male , Female , Aged , Middle Aged , Prospective Studies , Risk Assessment , Retrospective Studies , Anti-Bacterial Agents/therapeutic use , Aged, 80 and over , Adult , Risk Factors
19.
Nat Commun ; 15(1): 1366, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38355558

ABSTRACT

Efficient pathogen enrichment and nucleic acid isolation are critical for accurate and sensitive diagnosis of infectious diseases, especially those with low pathogen levels. Our study introduces a biporous silica nanofilms-embedded sample preparation chip for pathogen and nucleic acid enrichment/isolation. This chip features unique biporous nanostructures comprising large and small pore layers. Computational simulations confirm that these nanostructures enhance the surface area and promote the formation of nanovortex, resulting in improved capture efficiency. Notably, the chip demonstrates a 100-fold lower limit of detection compared to conventional methods used for nucleic acid detection. Clinical validations using patient samples corroborate the superior sensitivity of the chip when combined with the luminescence resonance energy transfer assay. The enhanced sample preparation efficiency of the chip, along with the facile and straightforward synthesis of the biporous nanostructures, offers a promising solution for polymer chain reaction-free detection of nucleic acids.


Subject(s)
Nanostructures , Nucleic Acids , Humans , Microfluidics , Silicon Dioxide , Oligonucleotide Array Sequence Analysis/methods , Nucleic Acid Amplification Techniques
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