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BACKGROUND: Community infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have increased rapidly since the emergence of the Omicron strain. During the eighth and ninth pandemic waves-when movement restrictions in the community were eased-the all-case registration system was changed, and the actual status of infection became uncertain. METHODS: We conducted regular rapid antigen tests (R-RATs) once or twice a week as self-testing to examine the actual state of coronavirus disease (COVID-19) diagnosis among healthcare employees. RESULTS: Overall, 320 (1.42/day) and 299 (1.76/day) employees were infected in the eighth and ninth pandemic waves. During both periods, 59/263 doctors (22.4%), 335/806 nurses (41.6%), 92/194 administrative employees (47.4%), and 129/218 clinical laboratory technicians (59.2%) were infected. In the eighth wave, 56 of 195 employees were infected through close contact; in the ninth wave, 26 of 62 employees were infected. No significant difference was observed in the number of vaccinations between infected and non-infected employees. The positivity rate of R-RATs was 0.41% and 0.45% in the eighth and ninth waves. R-RATs detected infection in 212 and 229 employees during the eighth and ninth waves, respectively; the ratio of R-RAT-detected positive employees to those who reported infection was significantly higher during the ninth wave (odds ratio: 1.67, 95% confidence interval: 1.17-2.37, p < 0.001). CONCLUSIONS: The number of infected healthcare employees remained high during the eighth and ninth pandemic waves in Japan. The R-RAT is considered effective for detecting mild or asymptomatic COVID-19 at an early stage and at a high rate in healthcare employees.
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Prostate cancer (PCa) ranks as the second most common cancer in Japanese males, while bladder cancer (BC) holds the tenth spot. Among double urological cancers, the incidence of synchronous or metachronous BC and PCa is the highest. Reports on upper urinary tract (UUT) urothelial cancer (UC) in PCa patients are limited. Here, we present three cases of metachronous PCa and BC, with subsequent diagnosis of ureteral and renal pelvic cancer during the course of the disease. In the follow-up of patients with urological cancers, it is important to be aware not only of the progression of the initial cancer but also the potential development of a second cancer.
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(1) Background: Inflammatory responses induce the formation of both anti-tumor and pro-tumor neutrophils known as myeloid-derived suppressor cells (MDSCs). Intermittent intravesical infusion of Bacillus Calmette-Guérin (BCG) is an established cancer immunotherapy for non-muscle-invasive bladder cancer (NMIBC). However, the types of neutrophils induced via the inflammatory response to both tumor-bearing and BCG remain unclear. (2) Methods: We therefore analyzed neutrophil dynamics in the peripheral blood and urine of patients with NMIBC who received BCG therapy. Further, we analyzed the effects of BCG in a mouse intraperitoneal tumor model. (3) Results: BCG therapy induced the formation of CXCL10 and MHC class II-positive neutrophils in the urine of patients with NMIBC but did not induce MDSC formation. CXCL10- and MHC class II-expressing neutrophils were detected in peritoneal exudate cells formed after BCG administration. Partial neutrophil depletion using an anti-Ly6G antibody suppressed the upregulation of CXCL10 and MHC class II in neutrophils and reversed the anti-tumor activity of BCG in mouse models. (4) Conclusions: These results indicated that intracellular MHC class II- and CXCL10-expressing neutrophils indicate the state of anti-tumor activity induced via BCG. The status of neutrophils in mixed inflammation of immunosuppressive and anti-tumor responses may therefore be useful for evaluating immunological systemic conditions.
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The therapeutic outcome of immune checkpoint inhibition (ICI) can be improved through combination treatments with ICI therapy. Myeloid-derived suppressor cells (MDSCs) strongly suppress tumor immunity. MDSCs are a heterogeneous cell population, originating from the unusual differentiation of neutrophils/monocytes induced by environmental factors such as inflammation. The myeloid cell population consists of an indistinguishable mixture of various types of MDSCs and activated neutrophils/monocytes. In this study, we investigated whether the clinical outcomes of ICI therapy could be predicted by estimating the status of the myeloid cells, including MDSCs. Several MDSC indexes, such as glycosylphosphatidylinositol-anchored 80 kD protein (GPI-80), CD16, and latency-associated peptide-1 (LAP-1; transforming growth factor-ß1 precursor), were analyzed via flow cytometry using peripheral blood derived from patients with advanced renal cell carcinoma (n = 51) immediately before and during the therapy. Elevated CD16 and LAP-1 expressions after the first treatment were associated with a poor response to ICI therapy. Immediately before ICI therapy, GPI-80 expression in neutrophils was significantly higher in patients with a complete response than in those with disease progression. This is the first study to demonstrate a relationship between the status of the myeloid cells during the initial phase of ICI therapy and clinical outcomes.
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INTRODUCTION: Macrolides (MCs) are broad-spectrum antimicrobials with activity against many microorganisms. They are widely used, and the development of MC-resistant bacteria is a serious problem in Japan. It is therefore necessary to clarify the purpose and duration of administration, with the aim of promoting appropriate use. METHODS: Patients of all ages, for whom oral MCs were prescribed between 2016 and 2020 were included. They were divided into four groups based on the number of days per prescription. In the long-term treatment group, patients treated with MCs for ≥1000 days were specifically investigated for the purpose of treatment. RESULTS: Macrolide prescriptions increased from 2019 to 2020. Most patients received ≥28 days of treatment based on one prescription. During the study period, 1212 patients (28.6%) received a total of ≥50 days and 152 patients (3.6%) received a total of ≥1000 days of treatment. Approximately a third of long-term administrations were for nontuberculous mycobacterial infections (NTMs), and 18.3% of patients with NTMs were treated with MCs alone. In addition, many MCs were administered for their anti-inflammatory effects on neutrophils. CONCLUSIONS: Owing to their pleiotropic effects, MCs may also be administered for the treatment of noninfectious diseases. In general, the long-term administration of antimicrobials contradicts the strategy for the suppression of resistant bacteria. It is thus important to understand the actual clinical utility of MCs and the purpose and duration of administration. In addition, strategies for the appropriate use of MCs are required for each medical institution.
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Antibacterianos , Antiinfecciosos , Humanos , Antibacterianos/uso terapéutico , Antiinfecciosos/uso terapéutico , Macrólidos/uso terapéutico , Prescripciones de Medicamentos , Inhibidores de la Síntesis de la ProteínaRESUMEN
Chronic heart failure (HF) has various phenotypes. It is accompanied by repeated hospitalizations over a long period. Therefore, accumulating long-term observational data of patients with various backgrounds is important to establish a prediction technology for the exacerbation of HF. In a patient with chronic right-sided HF caused by cor pulmonale, heart sounds and electrocardiograms were recorded at home or our hospital twice a week for 7â¯months including the stable (31â¯days), pre-exacerbation (2â¯weeks just before the onset of exacerbation), and hospitalization periods and quantified as cardiac acoustic biomarkers (CABs) using AUDICOR technology (Inovise Medical, Inc., Portland, OR, USA). The relationship between the change in CABs and hospitalization events due to HF were investigated. During the pre-exacerbation period just before the onset of exacerbation of HF leading to hospitalization, inaudible changes in the third heart sound (S3) strength that were probably derived from the right heart were observed. Although the values of the fourth heart sound (S4) strength were high during the stable and pre-exacerbation period, values decreased markedly during hospitalization. These findings suggest that CABs including S3 and S4 are useful for the early detection of signs of HF exacerbation. Learning Objective: In a case of chronic right-sided heart failure, the change in the third heart sound (S3) caused by the right ventricle could be detected using cardiac acoustic biomarkers in exacerbations of heart failure. Even if S3 is inaudible by auscultation, it is possible to observe its changes using quantification technology.
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BACKGROUND: Several clear cell renal cell carcinoma (ccRCC) cases harbour fibroblast growth factor receptor 4 (FGFR4) gene copy number (CN) gains. In this study, we investigated the functional contribution of FGFR4 CN amplification in ccRCC. METHODS: The correlation between FGFR4 CN determined via real-time PCR and protein expression evaluated using western blotting and immunohistochemistry was assessed in ccRCC cell lines (A498, A704, and 769-P), a papillary RCC cell line (ACHN), and clinical ccRCC specimens. The effect of FGFR4 inhibition on ccRCC cell proliferation and survival was assessed via either RNA interference or using the selective FGFR4 inhibitor BLU9931, followed by MTS assays, western blotting, and flow cytometry. To investigate whether FGFR4 is a potential therapeutic target, a xenograft mouse model was administered BLU9931. RESULTS: 60% of ccRCC surgical specimens harboured an FGFR4 CN amplification. FGFR4 CN was positively correlated with its protein expression. All ccRCC cell lines harboured FGFR4 CN amplifications, whereas ACHN did not. FGFR4 silencing or inhibition attenuated intracellular signal transduction pathways, resulting in apoptosis and suppressed proliferation in ccRCC cell lines. BLU9931 suppressed tumours at a tolerable dose in the mouse model. CONCLUSION: FGFR4 contributes to ccRCC cell proliferation and survival following FGFR4 amplification, making it a potential therapeutic target for ccRCC.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Animales , Ratones , Carcinoma de Células Renales/patología , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos/metabolismo , Línea Celular Tumoral , Proliferación Celular , Neoplasias Renales/patología , Regulación Neoplásica de la Expresión GénicaRESUMEN
We evaluated the humoral and cellular immune responses and safety of the third severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine with a longer interval after the second vaccination in kidney transplant recipients (KTRs). We enrolled 54 kidney transplant recipients without a history of coronavirus disease 2019 (COVID-19), who received a third dose of the vaccine. We assessed anti-SARS-CoV-2 spike antibody and antigen-specific T cells using enzyme-linked immunospot (ELISpot) against the spike protein at baseline, after the second vaccination, and after the third vaccination. We also evaluated the adverse events related to each dose of the vaccine. The duration between the second and third vaccinations was 7 ± 1 month. All 17 (100%) KTRs with anti-SARS-CoV-2 antibody positivity after the second vaccination and 27 of 37 (73%) KTRs without anti-SARS-CoV-2 antibody positivity after the second vaccination were positive for anti-SARS-CoV-2 antibodies (p=0.022). Anti-SARS-CoV-2 antibody titers were significantly higher than those after the second vaccination (p<0.001). Age ≥ 60 years and lymphocyte count < 1150/mm3 were confirmed as risk factors for anti-SARS-CoV-2 antibody negativity after the third vaccination in multivariate regression analysis. ELISpot cytokine activities were positive after the third vaccination in 26 of 29 (90%) KTRs with ELISpot cytokine activity positivity after the second vaccination and 12 of 24 (50%) KTRs without ELISpot cytokine activity after the second vaccination. The rate of change in cytokine activity after the third vaccination was significantly higher than that after the second vaccination (p<0.001). Only lymphocyte counts less than 1150/mm3 were confirmed as risk factors for ELISpot cytokine activity negativity in the multivariate regression analysis. Systemic adverse events classified as greater than moderate did not differ for each vaccine dose. None of the patients showed clinical symptoms of acute rejection. The third SARS-CoV-2 mRNA vaccine administration, with a longer interval after the second vaccination, improved humoral and cellular immune responses to SARS-CoV-2 mRNA vaccines without severe adverse effects in the KTRs.
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Vacunas contra la COVID-19 , COVID-19 , Inmunidad Celular , Inmunidad Humoral , Trasplante de Riñón , Humanos , Persona de Mediana Edad , Anticuerpos Antivirales/sangre , COVID-19/prevención & control , Vacunas contra la COVID-19/inmunología , Citocinas , SARS-CoV-2 , Vacunación , Inmunización SecundariaRESUMEN
Since an elevation of pulmonary artery pressure (PAP) often precedes clinical worsening of heart failure (HF), early and non-invasive detection of this sign is useful in HF care. This study aimed to assess whether cardiac acoustic biomarkers (CABs) are associated with the elevation of PAP in patients with HF. Patients with HF scheduled to undergo right heart catheterization were prospectively enrolled. CABs were concurrently recorded during catheterization at rest (baseline) and while applying a handgrip (exercise). Forty-nine patients were included in the analysis, and their mean PAP significantly increased after exercise compared to baseline. Several CABs correlated significantly with mean PAP by absolute values, among which S2 Width (r = 0.354; p = 0.014 and r = 0.363; p = 0.010) and S3 Strength (r = 0.375; p = 0.009 and r = 0.386; p = 0.007) were consistent throughout baseline and exercise. The response of CABs to exercise-induced PAP elevation was divided into two patterns: increasing and decreasing. The frequency of cardiac index below 2.2 mL/m2 was significantly higher in the decreasing pattern. CABs related to S2 and S3 showed significant correlations with absolute PAP values both at baseline and after exercise in patients with HF, but no significant correlations between their changes from baseline to post-exercise were observed in this study population. Further research is therefore needed to assess whether CABs can sensitively reflect changes in PAP according to HF status and underlying phenotypes.
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(1) Background: Extracellular signal-regulating kinase 5 (ERK5) has been implicated in many cellular functions, including survival, proliferation, and vascularization. Our objectives were to examine the expression and effect of ERK5 in clear cell renal cell carcinoma (ccRCC). (2) Methods: The expressions of ERK5 and its regulating micro-RNA miR-143 were investigated using immunohistochemistry and quantitative reverse transcriptase PCR in surgical specimens of ccRCC patients. With invitro and in vivo studies, we used pharmacologic ERK5 inhibitor XMD8-92, RNA interference, pre-miR-143 transduction, Western blotting, MTS assay, apoptosis assay, and subcutaneous xenograft model. (3) Results: A strong ERK5 expression in surgical specimen was associated with high-grade (p = 0.01), high-recurrence free rate (p = 0.02), and high cancer-specific survival (p = 0.03). Expression levels of ERK5 and miR-143 expression level were correlated (p = 0.049). Pre-miR-143 transduction into ccRCC cell A498 suppressed ERK5 expression. ERK5 inhibition enhanced cyclin-dependent kinase inhibitor p21 expression and decreased anti-apoptotic molecules BCL2, resulting in decreased cell proliferation and survival both in ccRCC and endothelial cells. In the xenograft model, ERK5 inhibitor XMD8-92 suppressed tumor growth. (4) Conclusions: ERK5 is regulated by miR-143, and ERK5 inhibition is a promising target for ccRCC treatment.
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Carcinoma de Células Renales , Neoplasias Renales , MicroARNs , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Proliferación Celular/genética , Células Endoteliales/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Renales/genética , Neoplasias Renales/patología , MicroARNs/metabolismoRESUMEN
We report a case of bacteremia caused by Bacillus subtilis variant natto after a gastrointestinal perforation in a patient in Japan. Genotypic and phenotypic studies of biotin identified B. subtilis var. natto. This case and 3 others in Japan may have been caused by consuming natto (fermented soybeans).
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Bacteriemia , Alimentos de Soja , Bacillus subtilis/genética , Bacteriemia/diagnóstico , Humanos , JapónRESUMEN
OBJECTIVES: We evaluated whether the treatment history of low-dose rituximab affected safety profiles, and humoral and cellular responses induced by severe acute respiratory syndrome coronavirus 2 messenger ribonucleic acid vaccine in healthy controls and kidney transplant recipients. METHODS: We enrolled 10 healthcare workers as controls, 22 kidney transplant recipients with rituximab, and 36 kidney transplant recipients without rituximab without history of coronavirus disease 2019 who received two doses of vaccine. We assessed anti-severe acute respiratory syndrome coronavirus 2 spike antibody and the antigen-specific T cells using enzyme-linked immunospot against spike protein at baseline and after two doses of vaccine. RESULTS: All controls showed anti-severe acute respiratory syndrome coronavirus 2 antibody seroconversion and enzyme-linked immunospot positivity. Only 19/58 (33%) kidney transplant recipients experienced anti-severe acute respiratory syndrome coronavirus 2 antibody seroconversion and 31/58 (53%) kidney transplant recipients developed enzyme-linked immunospot assay positivity after vaccination. The anti-severe acute respiratory syndrome coronavirus 2 antibody seroconversion rate and enzyme-linked immunospot assay positivity rate after vaccination were not significantly different between kidney transplant recipients with or without rituximab. Multivariate regression analysis demonstrated rituximab was not associated with a lack of humoral and cellular responses to the vaccine. CONCLUSIONS: Low-dose rituximab in kidney transplant recipients did not affect humoral or cellular responses to the severe acute respiratory syndrome coronavirus 2 messenger ribonucleic acid vaccine without severe systemic adverse events including the deterioration of kidney function.
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COVID-19 , Trasplante de Riñón , Vacunas Virales , Humanos , Vacunas contra la COVID-19/efectos adversos , SARS-CoV-2 , COVID-19/prevención & control , Rituximab/efectos adversos , Trasplante de Riñón/efectos adversos , Vacunas Virales/efectos adversos , Anticuerpos Antivirales , ARN , Receptores de Trasplantes , Vacunas de ARNmRESUMEN
Accompanied by the development of systemic therapy for metastatic renal cell carcinoma, the concept of focal treatment, including surgical treatment, has been changing. Although immediate cytoreductive nephrectomy was essentially considered for synchronous metastatic renal cell carcinoma patients, the CARMENA trial and SURTIME trial revealed the negative impact of immediate cytoreductive nephrectomy. Therefore, immediate cytoreductive nephrectomy is currently considered only for a limited number of patients. Besides, deferred cytoreductive nephrectomy seems to have efficacy for overall survival in prior retrospective studies. Two randomized controlled trials, the PROBE trial (NCT04510597) and the NORDIC-SUN trial (NCT03977571), are underway to elucidate deferred cytoreductive nephrectomy. Metastasectomy is also considered in metastatic renal cell carcinoma patients because previous studies demonstrated the overall survival benefit of metastasectomy. However, since all reports were retrospective studies, physicians could exclude the patients who were not expected to show the efficacy of metastasectomy. Therefore, an adequate patient selection for metastasectomy is important. A common factor predicting better overall survival was complete resection. Radiotherapies for metastatic lesions during systemic therapy showed approximately 90% local disease control rate at 1 year. However, no report has demonstrated that radiotherapy improves survival so far. Since surgical and focal treatments for metastatic renal cell carcinoma patients generally have minimal evidence, further investigations are needed.
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Carcinoma de Células Renales , Neoplasias Renales , Carcinoma de Células Renales/secundario , Carcinoma de Células Renales/cirugía , Procedimientos Quirúrgicos de Citorreducción , Humanos , Neoplasias Renales/cirugía , Nefrectomía , Estudios RetrospectivosRESUMEN
CASE: We experienced 2 cases of these entrapments. In the first case, the entrapment was identified immediately and treated successfully. In the second case, the entrapment was diagnosed after union when the disturbance of wrist flexion became apparent. CONCLUSION: When there is a longitudinal fracture line at the vicinity of the second compartment, the entrapment of extensors should be suspected even when acceptable overall alignment is accomplished.
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Fracturas del Radio , Atrapamiento del Tendón , Humanos , Radio (Anatomía) , Fracturas del Radio/complicaciones , Fracturas del Radio/diagnóstico por imagen , Fracturas del Radio/cirugía , Atrapamiento del Tendón/diagnóstico por imagen , Atrapamiento del Tendón/etiología , Atrapamiento del Tendón/cirugía , Tendones , MuñecaRESUMEN
PURPOSE: Mitochondrial disease can affect many organs, including the brain, nerves, heart, liver, eyes, ears, pancreas, and kidneys. Kidney transplantation is a treatment option for renal failure due to mitochondrial disease; however, the prognosis of patients who undergo kidney transplantation for mitochondrial disease is unknown. Here we evaluated the outcomes of kidney transplant recipients with mitochondrial disease. METHODS: Clinical data were obtained from 4 kidney transplantation recipients who were followed at our department. Of the 4 transplantations, 3 were performed in our department: 2 patients received kidneys from their fathers, and a third from his wife. The fourth recipient received a kidney from her mother-who had a mitochondrial genetic abnormality-at another hospital. Of the 4 recipients, 3 were diagnosed with mitochondrial disease before the transplantation, and the fourth was diagnosed after. All recipients had sensorineural deafness and diabetes mellitus, and only 1 had a history of encephalopathy and stroke-like episodes before the transplantation. RESULTS: One patient died 2 years after transplantation due to encephalopathy progression with stable kidney function. The grafted kidney of the patient who received it from her mother lost function at 5 years post-transplantation. A graft biopsy revealed focal segmental glomerular sclerosis due to mitochondrial disease. The other patients' kidney functions remained stable. None of the recipients experienced rejection. CONCLUSIONS: In kidney transplantation for mitochondrial disease, attention should be paid to the exacerbation of comorbidities, while careful consideration should be given to donors with a mitochondrial genetic abnormality.
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Trasplante de Riñón , Enfermedades Mitocondriales , Trasplantes , Femenino , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Trasplante de Riñón/efectos adversos , Enfermedades Mitocondriales/complicaciones , Enfermedades Mitocondriales/genética , Enfermedades Mitocondriales/cirugía , Donantes de TejidosRESUMEN
BACKGROUND: Body composition changes 1 year after kidney transplant (KT) have been studied extensively. However, the number of reports on midterm body composition changes has been limited. METHODS: The medical records and computed tomography scans of 10 living kidney recipients (6 men, 4 women) before KT and at 1, 3, and 5 years post KT were analyzed. Each patient's body mass index was calculated, and the skeletal muscle mass was evaluated using the skeletal muscle mass index and psoas muscle mass index. Each patient's abdominal adipose tissue mass was also quantified by examining the visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and VAT/SAT ratios. These changes were assessed using repeated-measures analysis of variance. RESULTS: The body mass index, skeletal muscle mass index, and psoas muscle mass index values did not differ significantly between the pre-KT and 1-, 3-, and 5-year post KT measurements. Conversely, a significant difference was found in the average VAT, SAT, and VAT/SAT ratio values between the pre-KT and at 1, 3, and 5 years post KT (P < .05). The average VAT measurements before and at 1, 3, and 5 years post KT were 66, 94, 108, and 113 cm2, respectively, indicating an increasing trend over time. CONCLUSIONS: We observed an increase in the VAT, SAT, and VAT/SAT ratio in patients at 1, 3, and 5 years post KT.
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Trasplante de Riñón , Tejido Adiposo , Composición Corporal , Índice de Masa Corporal , Femenino , Humanos , Grasa Intraabdominal/diagnóstico por imagen , Trasplante de Riñón/efectos adversos , Masculino , Grasa Subcutánea/diagnóstico por imagenRESUMEN
There are limited reports of patients with prosthetic valve infective endocarditis (IE) or recurrent IE due to highly beta-lactam-resistant viridans group streptococci. We present a case in which a patient with native valve IE due to beta-lactam-susceptible Streptococcus oralis developed prosthetic valve IE due to highly beta-lactam-resistant S. oralis . A 79-year-old man with a history of native aortic valve IE caused by beta-lactam-susceptible S. oralis 21 months prior to admission and aortic valve replacement was admitted to our hospital with a 2-week history of general malaise and low-grade fever. Transesophageal echocardiography showed a 20 mm vegetation on the prosthetic aortic valve, and emergency cardiovascular surgery was performed on admission day 2. Three sets of blood cultures on admission were positive for highly beta-lactam-resistant S. oralis . Vancomycin and cefazolin were administered as initial treatment. After the surgery, the patient was given vancomycin and gentamicin for 2 weeks, followed by vancomycin for 4 weeks. He was relapse-free at the 6-month follow-up. For patients with native valve IE due to S. oralis who have undergone valve replacement more than 1 year earlier, given the possibility of methicillin-resistant Staphylococcus aureus as well as S. oralis resistance to beta-lactams, it may be advisable to start vancomycin as an initial treatment and continue it until the infecting micro-organism has been proven to be susceptible to beta-lactams.