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Abstract This study aims to figure out the worldwide prevalence of anticancer therapy-associated acute kidney injury (AKI) and tubulointerstitial nephritis (TIN) and the relative risk of each cancer drug. We conducted an analysis of VigiBase, the World Health Organization pharmacovigilance database, 1967–2023 via disproportionate Bayesian reporting method. We further categorized the anticancer drugs into four groups: cytotoxic therapy, hormone therapy, immunotherapy, and targeted therapy. Reporting odds ratio (ROR) and information component (IC) compares observed and expected values to investigate the associations of each category of anticancer drugs with AKI and TIN. We identified 32,722 and 2056 reports (male, n = 17,829 and 1,293) of anticancer therapy-associated AKI and TIN, respectively, among 4,592,036 reports of all-drug caused AKI and TIN. There has been a significant increase in reports since 2010, primarily due to increased reports of targeted therapy and immunotherapy. Immunotherapy exhibited a significant association with both AKI (ROR: 8.92; IC0.25: 3.06) and TIN (21.74; 4.24), followed by cytotoxic therapy (7.14; 2.68), targeted therapy (5.83; 2.40), and hormone therapy (2.59; 1.24) for AKI, and by cytotoxic therapy (2.60; 1.21) and targeted therapy (1.54; 0.61) for TIN. AKI and TIN were more prevalent among individuals under 45 years of age, with a female preponderance for AKI and males for TIN. These events were reported in close temporal relationship after initiation of the respective drug (16.53 days for AKI and 27.97 days for TIN), and exhibited a high fatality rate, with 23.6% for AKI and 16.3% for TIN. These findings underscore that kidney-related adverse drug reactions are of prognostic significance and strategies to mitigate such side effects are required to optimize anticancer therapy.

Abstract Background IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis, although the definitive markers are unknown. We aimed to investigate the clinical significance of urinary cytokines in patients with IgAN. Methods From 2009 to 2018, the patients were divided into three groups: IgAN (n = 191), disease control (n = 53), and normal control (n = 76). We used a multiplex enzyme-linked immunosorbent assay to measure 16 selected urinary inflammatory cytokines, evaluated the correlation between clinical and pathological features following regression analysis on progression. Results The IgAN group exhibited significantly different levels of urinary cytokines compared to the normal control and disease control groups. Urinary levels of B-cell-activating factor, vascular endothelial growth factor receptor-2, monocyte chemoattractant protein-1, C–X–C motif chemokine 10, C–X–C motif ligand 16, epidermal growth factor (EGF), endocan, endostatin, growth/differentiation factor-15 (GDF-15), interleukin-6 (IL-6), mannose-binding lectin, transferrin receptor, and kidney injury molecule-1 were significantly correlated with both the estimated glomerular filtration rate and urine protein–creatinine ratio. In a multivariate Cox regression analysis, urinary EGF (hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.17–0.95, P = 0.04), GDF-15 (HR 2.45, 95% CI 1.01–5.94, P = 0.048), and IL-6 (HR 3.02, 95% CI 1.05–8.64, P = 0.04) were associated with progression in IgAN. Conclusions Urinary inflammatory biomarkers may serve as alternative predictive biomarkers in patients with IgAN. Further studies are needed to elucidate the physiological mechanisms and confirm the results.

Abstract Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. The clinical relevance of 11 urinary exosomal microRNAs (miRNAs) was evaluated in patients with IgAN. From January 2009 to November 2018, IgAN (n = 93), disease control (n = 11), and normal control (n = 19) groups were enrolled. We evaluated the expression levels of urinary exosomal miRNAs at the baseline and their relationship with clinical and pathologic features. This study aimed to discriminate statistically powerful urinary exosomal miRNAs for the prognosis of IgAN. Urinary miRNA levels of miR-16-5p, miR-29a-3p, miR-124-3p, miR-126-3p, miR-199a-3p, miR-199b-5p, and miR-335-3p showed significant correlation with both estimated glomerular filtration rate (eGFR) and urine protein-to-creatinine ratio (uPCR). In univariate regression analysis, age, body mass index, hypertension, eGFR, uPCR, Oxford classification E, and three miRNAs (miR-16-5p, miR-199a-3p, and miR-335-3p) were associated with disease progression in patients with IgAN. The area under the curve (AUC) of miR-199a-3p was high enough (0.749) without any other clinical or pathologic factors, considering that the AUC of the International IgAN Risk Prediction Tool was 0.853. Urinary exosomal miRNAs may serve as alternative prognostic biomarkers of IgAN with further research.

Background Recently, the target systolic blood pressure (BP) 20 years old and had estimated glomerular filtration rate 15 to 60 mL/min per 1.73 m2 during 2009 to 2011 were included from the database of Korean National Health Insurance Service and were followed up to 2018. Participants were categorized by BP as

Abstract Little is known about the prevalence of chronic kidney disease (CKD) during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to investigate the long-term trends in CKD prevalence from South Korea including the early pandemic. We used data from 108,152 Korean adults from 2007 to 2020 obtained from a representative longitudinal serial study. We defined CKD as a condition when the participant’s estimated glomerular filtration rate was

Dialysis patients are more likely to die or become hospitalized from coronavirus disease 2019 (COVID-19). Currently, only a few studies have evaluated the efficacy of a fourth booster vaccination in hemodialysis (HD) patients and there is not enough evidence to recommend for or against a fourth booster vaccination. This study compared the humoral response and disease severity of patients on HD who received either three or four doses of COVID-19 vaccine. A total of 88 patients were enrolled. Humoral response to vaccination was measured by quantifying immunoglobulin G levels against the receptor binding domain of SARS-CoV-2 (anti-RBD IgG) at five different times and plaque reduction neutralization tests (PRNT) at two different times after vaccination over a period of 18 months. Antibody levels were measured at approximately two-month intervals after the first and second dose, then four months after the third dose, and then one to six months after the fourth dose of vaccine. PRNT was performed two months after the second and four months after the third dose of vaccine. We classified patients into four groups according to the number of vaccine doses and presence of COVID-19 infection. Severe infection was defined as hospital admission for greater than or equal to two weeks or death. There was no difference in antibody levels between naïve and infected patients except after a fourth vaccination, which was effective for increasing antibodies in infection-naïve patients. Age, sex, body mass index (BMI), dialysis vintage, and presence of diabetes mellitus (DM) did not show a significant correlation with antibody levels. Four patients who experienced severe COVID-19 disease tended to have lower antibody levels prior to infection. A fourth dose of SARS-CoV-2 vaccine significantly elevated antibodies in infection-naïve HD patients and may be beneficial for HD patients who have not been previously infected with SARS-CoV-2 for protection against severe infection.

BackgroundWhether or not a single-dose Ad26.COV2.S prime and boost vaccination induces sufficient immunity is unclear. Concerns about the increased risk of breakthrough infections in the Ad26.COV2.S-primed population have also been raised.MethodsA prospective cohort study was conducted. Participants included healthy adults who were Ad26.COV2.S primed and scheduled to receive a booster vaccination with BNT162b2, mRNA-1273, or Ad26.COV2.S. The IgG anti-receptor binding domain (RBD) antibody titers, neutralizing antibody (NAb) titers (against wild type [WT] and Omicron [BA.1 and BA.5]), and Spike-specific interferon-γ responses of the participants were estimated at baseline, 3–4 weeks, 3 months, and 6 months after booster vaccination.ResultsA total of 89 participants were recruited (26 boosted with BNT162b2, 57 with mRNA-1273, and 7 with Ad26.COV2.S). The IgG anti-RBD antibody titers of all participants were significantly higher at 6 months post-vaccination than at baseline. The NAb titers against WT at 3 months post-vaccination were 359, 258, and 166 in the participants from the BNT162b2-, mRNA-1273-, and Ad26.COV2.S-boosted groups, respectively. Compared with those against WT, the NAb titers against BA.1/BA.5 were lower by 23.9/10.9-, 16.6/7.4-, and 13.8/7.2-fold in the participants from the BNT162b2-, mRNA-1273-, and Ad26.COV2.S-boosted groups, respectively, at 3 months post-vaccination. Notably, the NAb titers against BA.1 were not boosted after Ad26.COV2.S vaccination. Breakthrough infections occurred in 53.8%, 62.5%, and 42.9% of the participants from the BNT162b2-, mRNA-1273-, and Ad26.COV2.S-boosted groups, respectively. No significant difference in humoral and cellular immunity was found between individuals with and without SARS-CoV-2 breakthrough infections.ConclusionBooster vaccination elicited acceptable humoral and cellular immune responses in Ad26.COV2.S-primed individuals. However, the neutralizing activities against Omicron subvariants were negligible, and breakthrough infection rates were remarkably high at 3 months post-booster vaccination, irrespective of the vaccine type. A booster dose of a vaccine containing the Omicron variant antigen would be required.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections and hospitalization in infants and young children. Here, we analyzed the genetic diversity of RSV using partial G gene sequences in 84 RSV-A and 78 RSV- B positive samples collected in Seoul, South Korea, for 10 consecutive years, from 2010 to 2019. Our phylogenetic analysis revealed that RSV-A strains were classified into either the ON1 (80.9%) or NA1 (19.0%) genotypes. On the other hand, RSV-B strains demonstrated diversified clusters within the BA genotype. Notably, some sequences designated as BA-SE, BA-SE1, and BA-DIS did not cluster with previously identified BA genotypes in the phylogenetic trees. Despite this, they did not meet the criteria for the assignment of a new genotype based on recent classification methods. Selection pressure analysis identified three positive selection sites (amino acid positions 273, 274, and 298) in RSV-A, and one possible positive selection site (amino acid position 296) in RSV-B, respectively. The mean evolutionary rates of Korean RSV-A from 1999 to 2019 and RSV-B strains from 1991 and 2019 were estimated at 3.51 × 10-3 nucleotides (nt) substitutions/site/year and 3.32 × 10-3 nt substitutions/site/year, respectively. The population dynamics in the Bayesian skyline plot revealed fluctuations corresponding to the emergence of dominant strains, including a switch of the dominant genotype from NA1 to ON1. Our study on time-scaled cumulative evolutionary analysis contributes to a better understanding of RSV epidemiology at the local level in South Korea.

Abstract Background Prompt and accurate identification of carbapenemase production is essential for appropriate treatment and infection control. NG-Test Carba 5 (termed herein “Carba 5”; NG Biotech, Guipry, France) is a multiplex immunochromatographic assay for the rapid phenotypic identification of five major carbapenemases (KPC, NDM, VIM, IMP, and OXA-48-like) from bacterial isolates. This study aimed to evaluate the diagnostic performance of Carba 5 and its impact on the turn-around-time in a clinical microbiology laboratory. Results Carba 5 was retrospectively evaluated using 78 carbapenemase producers and 23 non-carbapenemase producers confirmed by PCR and sequencing. The performance and time required for carbapenemase identification were prospectively evaluated using 47 carbapenem resistant Enterobacteriaceae isolates, and the results were compared to those obtained using Xpert Carba-R (Cepheid, Sunnyvale, CA, USA). For the bacterial isolates included in retrospective and prospective evaluation, the Carba 5 assay correctly identified 147 isolates except one isolate with a sensitivity of 99.13% (95% CI 95.25–99.98%) and specificity of 100% (95% CI 89.42–100%). The Carba 5 assay missed one VIM-1 among 13 VIM producers. The assay showed a sensitivity of 92.31% (95% CI 63.97–99.81%) for detecting VIM and 100% for detecting KPC, NDM, OXA-48-like, and IMP. Compared to the Xpert Carba-R assay, Carba 5 exhibited 100% agreement and was more time-efficient (median time 24 min vs. 1 h 11 min). Conclusions The Carba 5 assay has potential as an alternative to molecular methods for detecting major carbapenemases from bacterial isolates in a clinical microbiology laboratory. Compared to the Xpert Carba-R, Carba 5 turns out to be more affordable and time-efficient while showing a comparable performance, and may accelerate therapeutic and infection control decisions.

Evaluation of the safety and immunogenicity of new vaccine platforms is needed to increase public acceptance of coronavirus disease 2019 (COVID-19) vaccines. Here, we evaluated the association between reactogenicity and immunogenicity in healthy adults following vaccination by analyzing blood samples before and after sequential two-dose vaccinations of BNT162b2 and ChAdOx1 nCoV-19. Outcomes included anti-S IgG antibody and neutralizing antibody responses, adverse events, and proinflammatory cytokine responses. A total of 59 and 57 participants vaccinated with BNT162b2 and ChAdOx1 nCoV-19, respectively, were enrolled. Systemic adverse events were more common after the first ChAdOx1 nCoV-19 dose than after the second. An opposite trend was observed in BNT162b2 recipients. Although the first ChAdOx1 nCoV-19 dose significantly elevated the median proinflammatory cytokine levels, the second dose did not, and neither did either dose of BNT162b2. Grades of systemic adverse events in ChAdOx1 nCoV-19 recipients were significantly associated with IL-6 and IL-1β levels. Anti-S IgG and neutralizing antibody titers resulting from the second BNT162b2 dose were significantly associated with fever. In conclusion, systemic adverse events resulting from the first ChAdOx1 nCoV-19 dose may be associated with proinflammatory cytokine responses rather than humoral immune responses. Febrile reactions after second BNT162b2 dose were positively correlated with vaccine-induced immune responses rather than with inflammatory responses.

Summary: COVID-19 vaccines elicit humoral and cellular immune responses. Durable maintenance of vaccine-induced immunity is required for long-term protection of the host. Here, we examine activation and differentiation of vaccine-induced CD8+ T cells using MHC class I (MHC-I) multimers and correlations between early differentiation and the durability of CD8+ T cell responses among healthcare workers immunized with two doses of BNT162b2. The frequency of MHC-I multimer+ cells is robustly increased by BNT162b2 but decreases 6 months post-second vaccination to 2.4%–65.6% (23.0% on average) of the peak. MHC-I multimer+ cells dominantly exhibit phenotypes of activated effector cells 1–2 weeks post-second vaccination and gradually acquire phenotypes of long-term memory cells, including stem cell-like memory T (TSCM) cells. Importantly, the frequency of TSCM cells 1–2 weeks post-second vaccination significantly correlates with the 6-month durability of CD8+ T cells, indicating that early generation of TSCM cells determines the longevity of vaccine-induced memory CD8+ T cell responses.

Tuberculosis (TB) is one of the leading causes of infectious mortality from a single infectious agent, Mycobacterium tuberculosis (MTB). This study evaluated the performance of the newly developed BZ TB/NTM NALF assay, which integrated loop-mediated isothermal amplification and lateral flow immunochromatographic assay technologies, for the detection of MTB. A total of 80 MTB-positive samples and 115 MTB-negative samples were collected, all of which were confirmed by TB real-time PCR (RT-PCR) using either AdvanSureTM TB/NTM RT-PCR Kit or Xpert® MTB/RIF Assay. The performance of the BZ TB/NTM NALF assay was evaluated by calculating its sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in comparison to those of the RT-PCR methods. Compared to the RT-PCR, the sensitivity, specificity, PPV, and NPV of BZ TB/NTM NALF assay were 98.7%, 99.1%, 98.7%, and 99.1%, respectively. The concordance rate between BZ TB/NTM NALF and RT-PCR was 99.0%. Rapid and simple detection of MTB is essential for global case detection and further elimination of TB. The performance of the BZ TB/NTM NALF Assay is acceptable with a high concordance with RT-PCR, indicating that it is reliable for use in a low-resource environment.

We report a case of cellulitis caused by a novel Cupriavidus species identified using whole-genome sequence analysis. Subcutaneous tissue biopsies from the left lower leg of a 67-year-old man who suffered from cellulitis were cultured. Round, convex, gray and non-hemolytic colonies were recovered after 72-h incubation. 16S rRNA sequence analysis showed 98.6% similarity with Cupriavidus basilensis DSM 11853(T) in the NCBI database and 99.9% similarity with C. basilensis KF708 in the EzBioCloud database. Genomic analysis using the MiSeq platform (Illumina, USA) and the TrueBac ID database (ChunLab, Korea) revealed that the average nucleotide identity (ANI) of this strain with C. basilensis DSM 11853(T) was 87.6%. The patient was treated with oral cefditoren pivoxil for 9 weeks. This study is the first to report cellulitis caused by Cupriavidus species strain J1218. (Ann Clin Microbiol 2019;22:105 -109)

Abstract Background There are growing concerns regarding the spread of carbapenemase-producing organisms (CPOs) among patients in long-term care facilities (LTCFs) and hospitals in South Korea. We have established a screening protocol for the detection of CPOs in high-risk patients upon admission to intensive care units (ICUs). The diagnostic performance of the Xpert Carba-R assay was compared to that of rectal culture for CPO detection in high-risk patients upon ICU admission. Methods A total of 408 consecutive rectal swabs were obtained from December 2016 to December 2017. CPO screening was performed using the Xpert Carba-R assay (Cepheid, Sunnyvale, CA, USA). When a carbapenemase gene was detected, additional rectal swabs were incubated overnight and inoculated on chromID CARBA medium (bioMérieux, Marcy l’Etoile, France). Bacterial carbapenemase genes, including bla KPC, bla NDM, bla VIM, bla IMP-1, and bla OXA-48, were confirmed by conventional PCR. The diagnostic performance of the Carba-R assay was ascertained based on the culture results. Results The prevalence of CPO carriage was 7.4% according to the Carba-R assay and 3.7% according to rectal culture. The median Ct values of IMP-1 and KPC were significantly different (35.2 vs. 26.6, P = 0.0143). The overall sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the Carba-R assay were 100.0% (95% confidence interval [CI], 78.2–100.0), 96.7% (94.4–98.2), 53.6% (40.4–66.4) and 100.0% (99.0–100.0), respectively. Conclusions We demonstrated the prevalence of CPO carriage in high-risk patients upon ICU admission and evaluated the diagnostic performance of the Carba-R assay. The combined use of the Xpert Carba-R assay and culture produces rapid and reliable results for the active surveillance of rectal CPO in ICU patients.

Acute kidney injury (AKI) is a common clinical syndrome that is characterized by abnormal renal function and structure. The Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference in 2019 reviewed the stages of AKI and the definitions of AKI-related terminologies, and discussed the advances in the last decade. Along with serum creatinine level and urine output, more accurate novel biomarkers for predicting AKI are being applied for the early detection of renal dysfunction. A literature search was conducted in PubMed, Scopus, Medline, and ClinicalTrials.gov using the terms AKI and biomarker, combined with diagnosis, management, or prognosis. Because of the large volume of data (160 articles) published between 2005 and 2022, representative literature was chosen. A number of studies have demonstrated that new biomarkers are more sensitive in detecting AKI in certain populations than serum creatinine and urine output according to the recommendations from the Acute Disease Quality Initiative Consensus Conference. To be specific, there is a persistently unresolved need for earlier detection of patients with AKI before AKI progresses to a need for renal replacement therapy. Biomarker-guided management may help to identify a high-risk group of patients in progression to severe AKI, and decide the initiation time to renal replacement therapy and optimal follow-up period. However, limitations such as biased data to certain studied populations and absence of cutoff values need to be solved for worldwide clinical use of biomarkers in the future. Here, we provide a comprehensive review of biomarker-based AKI diagnosis and management and highlight recent developments.

OBJECTIVE--To improve quality and efficiency of care for elderly patients with type 2 diabetes, we introduced elderly-friendly strategies to the clinical decision support system (CDSS)-based ubiquitous healthcare (u-healthcare) service, which is an individualized health management system using advanced medical information technology. RESEARCH DESIGN AND METHODS--We conducted a 6-month randomized, con- trolled clinical trial involving 144 patients aged >60 years. Participants were randomly assigned to receive routine care (control, n = 48), to the self-monitored blood glucose (SMBG, n = 47) group, or to the u-healthcare group (n = 49). The primary end point was the proportion of patients achieving A1C <7% without hypoglycemia at 6 months. U-healthcare system refers to an individualized medical service in which medical instructions are given through the patient's mobile phone. Patients receive a glucometer with a public switched telephone network-connected cradle that automatically transfers test results to a hospital-based server. Once the data are transferred to the server, an automated system, the CDSS rule engine, generates and sends patient-specific messages by mobile phone. RESULTS--After 6 months of follow-up, the mean A1C level was significantly decreased from 7.8 ± 1.3% to 7.4 ± 1.0% (P < 0.001) in the u-healthcare group and from 7.9 ±1.0% to 7.7 ± 1.0% (P = 0.020) in the SMBG group, compared with 7.9 ± 0.8% to 7.8 ± 1.0% (P = 0.274) in the control group. The proportion of patients with A1C <7% without hypoglycemia was 30.6% in the u-healthcare group, 23.4% in the SMBG group (23.4%), and 14.0% in the control group (P < 0.05). CONCLUSIONS--The CDSS-based u-healthcare service achieved better glycemic control with less hypoglycemia than SMBG and routine care and may provide effective and safe diabetes management in the elderly diabetic patients. [ABSTRACT FROM AUTHOR]

We report the performance improvement of low-temperature coplanar indium–gallium–zinc–oxide (IGZO) thin-film transistors (TFTs) with a maximum process temperature of 230 °C. We treated F plasma on the surface of an SiO2 buffer layer before depositing the IGZO semiconductor by reactive sputtering. The field-effect mobility increases from 3.8 to 9.0 cm2 V−1·s−1, and the threshold voltage shift (ΔVth) under positive-bias temperature stress decreases from 3.2 to 0.2 V by F-plasma exposure. High-resolution transmission electron microscopy and atom probe tomography analysis reveal that indium fluoride (In-F) nanoparticles are formed at the IGZO/buffer layer interface. This increases the density of the IGZO and improves the TFT performance as well as its bias stability. The results can be applied to the manufacturing of low-temperature coplanar oxide TFTs for oxide electronics, including information displays.

BackgroundAdvanced information technology can be used when developing diagnostic and treatment strategies to provide better care for diabetic patients. However, the levels of need and demand for the use of technological advances have not been investigated in diabetic patients. We proposed and developed an individualized, ubiquitous (U)-healthcare service using advanced information technology for more effective glucose control. Prior to our service initiation, we surveyed patient needs and other pertinent information.MethodsDuring August 2009, we conducted a 34-item questionnaire survey among patients with diabetes who were older than 40 years in two certain hospitals in Korea.ResultsThe mean age of the 228 participants was 61.2±9 years, and males made up 49.1% of the sample. Seventy-one percent replied that they wanted individualized healthcare service, and they also wanted their health information to be delivered through mobile devices such as a cellular phone or a personal digital assistant (40.4%). Most patients had never heard of U-healthcare services (81.1%); however, after explaining the concept, 71.1% of participants responded that they would use the service if it was provided. Despite their willingness, participants were concerned about technical difficulty in using the service (26.3%) as well as the cost of the service (29.8%).ConclusionThe current study suggests that more than 70% of diabetic patients are interested in using U-healthcare services. To encourage widespread use, the application program or device of U-healthcare services should be simple, easy to use and affordable while also including a policy for the protection of private information.