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1.
Int J Clin Oncol ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38884877

ABSTRACT

BACKGROUND: It remains unclear which patients with biochemical recurrence after prostatectomy are most suitable for salvage radiotherapy. We evaluated the parameters related to outcomes. METHODS: We retrospectively evaluated patients who underwent salvage therapy for biochemical recurrence after prostatectomy between 2005 and 2019. This study aimed to evaluate biochemical recurrence-free survival (bRFS) after salvage radiotherapy and elucidate the parameters associated with bRFS. The bRFS rate was calculated using the Kaplan-Meier method, and the parameters associated with bRFS were evaluated using Cox regression analysis. RESULTS: This study included 67 patients treated with salvage radiotherapy with a median age of 67 years at salvage radiotherapy. The median follow-up period after salvage radiotherapy was 7.3 years. The 5-year bRFS rate following salvage radiotherapy was 47.1%. Univariate analysis showed that PSA doubling time < 6 months, positive surgical margin, and pathological Gleason score ≥ 8 were significantly associated with shorter bRFS (p < 0.001, p = 0.036, p = 0.047, respectively). Multivariable analysis showed that a PSA doubling time < 6 months and positive surgical margins were significantly associated with shorter bRFS (p = 0.001 and p = 0.018, respectively). No serious adverse events were observed. CONCLUSIONS: In our hospital, approximately half of the patients are under long-term control with salvage radiotherapy. A PSA doubling time of < 6 months and positive surgical margins were suggested to be associated with poor outcomes of salvage radiotherapy.

2.
Int J Urol ; 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822533

ABSTRACT

OBJECTIVES: To determine the effects of prophylactic urethrectomy (PU) on oncological and perioperative outcomes in patients with bladder cancer (BC) undergoing radical cystectomy (RC). METHODS: This retrospective study analyzed data on 1976 evaluable patients with BC who underwent RC. Patients were drawn from 36 institutions within the Japanese Urological Oncology Group. Oncological outcomes were compared using restricted mean survival times (RMSTs) based on inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves for non-urinary tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS). Interaction terms within IPTW-adjusted Cox regression models were examined to assess the heterogeneity of treatment effect based on the risk of urethral recurrence (UR). The association between PU, estimated blood loss (EBL), and the incidence of severe postoperative surgical complications (SPSCs) (Clavien-Dindo grade 3 or higher) was analyzed. RESULTS: Of 1976 patients, 1448 (73.3%) received PU. IPTW adjustment was used to balance baseline characteristics between the treatment groups. Within the 107-month window of patient monitoring, PU showed no survival benefits (NUTRFS difference: 0.2 months [95% confidence interval: -6.8 to 7.3]; CSS, 1.2 [-4.9 to 7.3]; OS, 0 [-6.5 to 6.5]). No significant interactions were observed with factors associated with UR, and PU was associated with unfavorable perioperative outcomes (EBL, 1179 mL vs. 983 mL; SPSC, 14.6% vs. 7.0%). CONCLUSIONS: This study showed that (1) PU was not associated with survival in patients with BC undergoing RC, regardless of UR-associated factors, and (2) PU was associated with unfavorable perioperative outcomes.

3.
Microbiome ; 12(1): 89, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38745230

ABSTRACT

BACKGROUND: Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets sensitised bladder tumours to irradiation by modifying the gut microbiota, along with clinical evidence of prebiotics enhancing anti-cancer immunity, we hypothesised that dietary fibre and its gut microbiota modification can radiosensitise tumours via secretion of metabolites and/or immunomodulation. We investigated the efficacy of high-fibre diets combined with irradiation in immunoproficient C57BL/6 mice bearing bladder cancer flank allografts. RESULT: Psyllium plus inulin significantly decreased tumour size and delayed tumour growth following irradiation compared to 0.2% cellulose and raised intratumoural CD8+ cells. Post-irradiation, tumour control positively correlated with Lachnospiraceae family abundance. Psyllium plus resistant starch radiosensitised the tumours, positively correlating with Bacteroides genus abundance and increased caecal isoferulic acid levels, associated with a favourable response in terms of tumour control. Psyllium plus inulin mitigated the acute radiation injury caused by 14 Gy. Psyllium plus inulin increased caecal acetate, butyrate and propionate levels, and psyllium alone and psyllium plus resistant starch increased acetate levels. Human gut microbiota profiles at the phylum level were generally more like mouse 0.2% cellulose profiles than high fibre profiles. CONCLUSION: These supplements may be useful in combination with radiotherapy in patients with pelvic malignancy. Video Abstract.


Subject(s)
Dietary Fiber , Dietary Supplements , Gastrointestinal Microbiome , Inulin , Mice, Inbred C57BL , Psyllium , Urinary Bladder Neoplasms , Animals , Mice , Gastrointestinal Microbiome/drug effects , Inulin/administration & dosage , Urinary Bladder Neoplasms/radiotherapy , Urinary Bladder Neoplasms/pathology , Humans , Female , Radiation Injuries/prevention & control , Intestines/microbiology , Intestines/radiation effects , CD8-Positive T-Lymphocytes
4.
J Microbiol Methods ; 221: 106929, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38599390

ABSTRACT

Utility of a recently developed long-read pipeline, Emu, was assessed using an expectation-maximization algorithm for accurate read classification. We compared it to conventional short- and long-read pipelines, using well-characterized mock bacterial samples. Our findings highlight the necessity of appropriate data-processing for taxonomic descriptions, expanding our understanding of the precise microbiome.


Subject(s)
Bacteria , High-Throughput Nucleotide Sequencing , Microbiota , RNA, Ribosomal, 16S , RNA, Ribosomal, 16S/genetics , Bacteria/genetics , Bacteria/classification , Bacteria/isolation & purification , Microbiota/genetics , High-Throughput Nucleotide Sequencing/methods , Sequence Analysis, DNA/methods , Algorithms , Nanopores , DNA, Bacterial/genetics
5.
Int J Urol ; 31(6): 662-669, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38424729

ABSTRACT

OBJECTIVES: The American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) 8th edition has proposed micrometastasis as a lymph node metastasis (LN+) of diameter ≤2 mm in prostate cancer. However, supporting evidence has not described. We evaluated LN+ patients' survival after radical prostatectomy (RP) based on the LN maximum tumor diameter (MTD). METHODS: Data from 561 LN+ patients after RP and pelvic LN dissection (PLND) treated between 2006 and 2019 at 33 institutions were retrospectively investigated. Patients were stratified by a LN+ MTD cutoff of 2 mm. Outcomes included castration resistance-free survival (CRFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: In total, 282 patients were divided into two groups (LN+ MTD >2 mm [n = 206] and ≤2 mm [n = 76]). Patients of LN+ status >2 mm exhibited significantly decreased CRFS and MFS, and poorer CSS and OS. No patients developed CRPC in the LN+ status ≤2 mm group when the PLND number was ≥14. Multivariate analysis showed the number of LN removed, RP Gleason pattern 5, and MTD in LN+ significantly predicted CRFS. CONCLUSIONS: Patients of LN+ status ≤2 mm showed better prognoses after RP. In all the patients in the ≤2-mm group, the progression to CRPC could be prevented with appropriate interventions, particularly when PLND is performed accurately. Our findings support the utility of the pN substaging proposed by the AJCC/UICC 8th edition; this will facilitate precision medicine for patients with advanced prostate cancer.


Subject(s)
Lymph Node Excision , Lymph Nodes , Lymphatic Metastasis , Neoplasm Staging , Prostatectomy , Prostatic Neoplasms , Humans , Male , Prostatectomy/methods , Prostatic Neoplasms/surgery , Prostatic Neoplasms/pathology , Prostatic Neoplasms/mortality , Aged , Middle Aged , Retrospective Studies , Lymphatic Metastasis/pathology , Japan , Lymph Node Excision/methods , Lymph Nodes/pathology , Lymph Nodes/surgery , Neoplasm Micrometastasis/pathology , Prognosis , East Asian People
6.
Asian J Endosc Surg ; 17(2): e13290, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38355902

ABSTRACT

In cases of rectal invasion by locally invasive prostate cancer (LAPC) leading to severe pain or bleeding, total pelvic exenteration (TPE) is necessary. Here, we present two cases of successful minimally invasive TPE: one performed laparoscopically for local recurrence with rectal bleeding after laparoscopic radical prostatectomy, and another done robotically for LAPC (clinical T4N1M0) accompanied by rectal bleeding. Medical treatments were ineffective in the latter case, and the tumor occupied a significant portion of the pelvis. We adopted a simultaneous transperineal approach and performed intracorporeal ileal conduit formation. Our cases highlight the challenging nature of minimally invasive TPE for symptomatic LAPC. Despite its complexity, these techniques prove viable and valuable in managing LAPC-related symptoms, emphasizing their practical utility in clinical settings.


Subject(s)
Pelvic Exenteration , Prostatic Neoplasms , Rectal Neoplasms , Male , Humans , Rectal Neoplasms/surgery , Rectal Neoplasms/pathology , Pelvic Exenteration/methods , Rectum/surgery , Prostatic Neoplasms/surgery , Prostatic Neoplasms/pathology , Prostatectomy , Neoplasm Recurrence, Local/surgery , Retrospective Studies
7.
BJU Int ; 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38344879

ABSTRACT

OBJECTIVE: To analyse the impact of histological discordance of subtypes (subtypes or divergent differentiation [DD]) in specimens from transurethral resection (TUR) and radical cystectomy (RC) on the outcome of the patients with bladder cancer receiving RC. PATIENTS AND METHODS: We analysed data for 2570 patients from a Japanese nationwide cohort with bladder cancer treated with RC between January 2013 and December 2019 at 36 institutions. The non-urinary tract recurrence-free survival (NUTR-FS) and overall survival (OS) stratified by TUR or RC specimen histology were determined. We also elucidated the predictive factors for OS in patients with subtype/DD bladder cancer. RESULTS: At median follow-up of 36.9 months, 835 (32.4%) patients had NUTR, and 691 (26.9%) died. No statistically significant disparities in OS or NUTR-FS were observed when TUR specimens were classified as pure-urothelial carcinoma (UC), subtypes, DD, or non-UC. Among 2449 patients diagnosed with pure-UC or subtype/DD in their TUR specimens, there was discordance between the pathological diagnosis in TUR and RC specimens. Histological subtypes in RC specimens had a significant prognostic impact. When we focused on 345 patients with subtype/DD in TUR specimens, a multivariate Cox regression analysis identified pre-RC neutrophil-lymphocyte ratio and pathological stage as independent prognostic factors for OS (P = 0.016 and P = 0.001, respectively). The presence of sarcomatoid subtype in TUR specimens and lymphovascular invasion in RC specimens had a marginal effect (P = 0.069 and P = 0.056, respectively). CONCLUSION: This study demonstrated that the presence of subtype/DD in RC specimens but not in TUR specimens indicated a poor prognosis. In patients with subtype/DD in TUR specimens, pre-RC neutrophil-lymphocyte ratio and pathological stage were independent prognostic factors for OS.

8.
Int J Clin Oncol ; 29(4): 464-472, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38316710

ABSTRACT

BACKGROUND: This study aimed to investigate factors, including the degree of hydronephrosis, that may be associated with decreased renal function after radical nephroureterectomy (RNU). METHODS: This study included 252 patients who underwent laparoscopic RNU with an estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73 m2 in three institutions. We assessed the association between hydronephrosis grade and perioperative renal function and performed a stepwise multivariate linear regression analysis to identify factors associated with postoperative eGFR. Patients with preoperative eGFR ≥ 50 ml/min/1.73 m2 were divided into a training set and an independent external validation set to develop a predictive model for postoperative renal function. RESULTS: The median preoperative and postoperative eGFR were 61.1 and 46.4 ml/min/1.73 m2, respectively. The eGFR preservation rates were 66.9%, 66.6%, 88.1%, and 100.0% in groups without, with mild, moderate, and severe hydronephrosis, respectively, and this difference was statistically significant (p < 0.001). Multivariate analysis revealed that factors predictive of postoperative eGFR included sex, preoperative eGFR, clinical T stage (cT3-4), and the presence of moderate or severe hydronephrosis. Our predictive model, based on these factors, positively correlated with actual postoperative renal function, and the similarity in categories with or without renal function insufficiency between predicted and actual postoperative renal functions was 78% in both training and validation sets. CONCLUSION: Moderate or severe hydronephrosis is associated with a modest postoperative decline in renal function, while mild hydronephrosis is not. Our predictive model may be useful in predicting postoperative renal function insufficiency and guiding decision-making for perioperative medical treatment.


Subject(s)
Carcinoma, Transitional Cell , Hydronephrosis , Laparoscopy , Renal Insufficiency , Humans , Nephroureterectomy , Nephrectomy , Carcinoma, Transitional Cell/surgery , Hydronephrosis/complications , Glomerular Filtration Rate , Kidney/surgery , Laparoscopy/adverse effects , Retrospective Studies
9.
Ann Surg Oncol ; 31(6): 3872-3879, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38353798

ABSTRACT

BACKGROUND: This study aimed to create a prognostic model to predict disease recurrence among patients with lymph node involvement but no prostate-specific antigen (PSA) persistence and to explore its clinical utility. METHODS: The study analyzed patients with lymph node involvement after pelvic lymph node dissection with radical prostatectomy in whom no PSA persistence was observed between 2006 and 2019 at 33 institutions. Prognostic factors for recurrence-free survival (RFS) were analyzed by the Cox proportional hazards model. RESULTS: Among 231 patients, 127 experienced disease recurrence. The factors prognostic for RFS were PSA level at diagnosis (≥ 20 vs. < 20 ng/mL: hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.09-2.52; P = 0.017), International Society of Urological Pathology grade group at radical prostatectomy (RP) specimen (group ≥ 4 vs. ≤ 3: HR, 1.63; 95% CI 1.12-2.37; P = 0.010), pathologic T-stage (pT3b/4 vs. pT2/3a: HR, 1.70; 95% CI 1.20-2.42; P = 0.0031), and surgical margin status (positive vs. negative: HR, 1.60; 95% CI 1.13-2.28; P = 0.0086). The prognostic model using four parameters were associated with RFS and metastasis-free survival. CONCLUSION: The prognostic model in combination with postoperative PSA value and number of lymph nodes is clinically useful for discussing treatment choice with patients.


Subject(s)
Lymph Nodes , Lymphatic Metastasis , Neoplasm Recurrence, Local , Prostate-Specific Antigen , Prostatectomy , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Prostatic Neoplasms/blood , Prostatectomy/methods , Prostate-Specific Antigen/blood , Middle Aged , Survival Rate , Follow-Up Studies , Prognosis , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/blood , Aged , Lymph Nodes/pathology , Lymph Nodes/surgery , Lymph Node Excision , Retrospective Studies , Neoplasm Staging , Neoplasm Grading , Margins of Excision
10.
Int J Clin Oncol ; 29(5): 602-611, 2024 May.
Article in English | MEDLINE | ID: mdl-38418804

ABSTRACT

BACKGROUND: Enfortumab vedotin is a novel antibody-drug conjugate used as a third-line therapy for the treatment of urothelial cancer. We aimed to elucidate the effect of enfortumab vedotin-related peripheral neuropathy on its efficacy and whether enfortumab vedotin-induced early electrophysiological changes could be associated with peripheral neuropathy onset. METHODS: Our prospective multicenter cohort study enrolled 34 patients with prior platinum-containing chemotherapy and programmed cell death protein 1/ligand 1 inhibitor-resistant advanced urothelial carcinoma and received enfortumab vedotin. The best overall response, progression-free survival, overall survival, and safety were assessed. Nerve conduction studies were also performed in 11 patients. RESULTS: The confirmed overall response rate and disease control rate were 52.9% and 73.5%, respectively. The median overall progression-free survival and overall survival were 6.9 and 13.5 months, respectively, during a median follow-up of 8.6 months. The patients with disease control had significantly longer treatment continuation and overall survival than did those with uncontrolled disease. Peripheral neuropathy occurred in 12.5% of the patients. The overall response and disease control rates were 83.3% and 100%, respectively: higher than those in patients without peripheral neuropathy (p = 0.028 and p = 0.029, respectively). Nerve conduction studies indicated that enfortumab vedotin reduced nerve conduction velocity more markedly in sensory nerves than in motor nerves and the lower limbs than in the upper limbs, with the sural nerve being the most affected in the patients who developed peripheral neuropathy (p = 0.011). CONCLUSION: Our results indicated the importance of focusing on enfortumab vedotin-induced neuropathy of the sural nerve to maximize efficacy and improve safety.


Subject(s)
Antibodies, Monoclonal , Peripheral Nervous System Diseases , Humans , Male , Female , Peripheral Nervous System Diseases/chemically induced , Aged , Prospective Studies , Middle Aged , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal/adverse effects , Aged, 80 and over , Neural Conduction/drug effects , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Carcinoma, Transitional Cell/drug therapy , Progression-Free Survival , Urologic Neoplasms/drug therapy , Urologic Neoplasms/pathology
11.
BMJ Case Rep ; 17(1)2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38272512

ABSTRACT

Congenital hypogonadotropic hypogonadism (CHH) is a genetically and clinically diverse disorder encompassing Kallmann syndrome (KS) and normosmic CHH (nCHH). Although mutations in numerous genes account for nearly 50% of CHH cases, a significant portion remains genetically uncharacterized. While most mutations follow the traditional Mendelian inheritance patterns, evidence suggests oligogenic interactions between CHH genes, acting as modifier genes to explain variable expressivity and incomplete penetrance associated with certain mutations.In this study, the proband presented with nCHH, while his son exhibited KS. We employed whole-exome sequencing (WES) to investigate the genetic differences between the two, and Sanger sequencing was used to validate the results obtained from WES.Genetic analysis revealed that both the proband and his son harboured a mutation in FGFR1 gene. Notably, an additional rare mutation in PROKR2 gene was exclusively identified in the son, which suggests the cause of the phenotypic difference between KS and nCHH.


Subject(s)
Hypogonadism , Kallmann Syndrome , Humans , Kallmann Syndrome/genetics , Mutation, Missense , Hypogonadism/genetics , Mutation , Family , Receptors, Peptide/genetics , Receptors, G-Protein-Coupled/genetics , Receptor, Fibroblast Growth Factor, Type 1/genetics
12.
Sci Rep ; 13(1): 21493, 2023 12 06.
Article in English | MEDLINE | ID: mdl-38057335

ABSTRACT

Coronavirus disease (COVID-19) has caused extensive mortality globally; therefore, biomarkers predicting the severity and prognosis of COVID-19 are essential. This study aimed to evaluate the application of presepsin (P-SEP) and thrombomodulin (TM), which are biomarkers of sepsis and endothelial dysfunction, respectively, in the prognosis of COVID-19. Serum P-SEP and TM levels from COVID-19 patients (n = 183) were measured. Disease severity was classified as mild, moderate I, moderate II, or severe based on hemoglobin oxygen saturation and the history of intensive care unit transfer or use of ventilation at admission. Patients in the severe group were further divided into survivors and non-survivors. P-SEP and TM levels were significantly higher in the severe group than those in the mild group, even after adjusting for creatinine values. In addition, TM levels were significantly higher in non-survivors than in survivors. Changes in the P-SEP levels at two time points with an interval of 4.1 ± 2.2 days were significantly different between the survivors and non-survivors. In conclusion, TM and continuous P-SEP measurements may be useful for predicting mortality in patients with COVID-19. Moreover, our data indicate that P-SEP and TM values after creatinine adjustment could be independent predictive markers, apart from renal function.


Subject(s)
COVID-19 , Sepsis , Humans , Biomarkers , Creatinine , Lipopolysaccharide Receptors , Peptide Fragments , Prognosis , Prospective Studies , Thrombomodulin
13.
Appl Environ Microbiol ; 89(12): e0161923, 2023 12 21.
Article in English | MEDLINE | ID: mdl-38051072

ABSTRACT

IMPORTANCE: Clostridium perfringens causes gas gangrene and food poisoning in humans, and monitoring this bacterium is important for public health. Although whole-genome sequencing is useful to comprehensively understand the virulence, resistome, and global genetic relatedness of bacteria, limited genomic data from environmental sources and developing countries hamper our understanding of the richness of the intrinsic genomic diversity of this pathogen. Here, we successfully accumulated the genetic data on C. perfringens strains isolated from hospital effluent and provided the first evidence that predicted pathogenic C. perfringens may be disseminated in the clinical environment in Ghana. Our findings suggest the importance of risk assessment in the environment as well as the clinical setting to mitigate the potential outbreak of C. perfringens food poisoning in Ghana.


Subject(s)
Clostridium Infections , Foodborne Diseases , Humans , Clostridium perfringens , Wastewater , Ghana , Foodborne Diseases/microbiology , Clostridium Infections/microbiology
14.
Drug Metab Pharmacokinet ; 53: 100506, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38029470

ABSTRACT

We previously reported that monoclonal antibodies (mAbs) with a high isoelectric point (pI) value tended to exhibit fast plasma clearance (CL) and large steady-state volume of distribution (Vdss) in mice. However, the positive correlation between pI, CL, and Vdss cannot be described by the reported physiologically based pharmacokinetic (PBPK) models, in which FcRn-mediated transcytosis of mAbs is set to be minimal compared to convection-mediated transport. To address this issue, physiological parameters (lymph flow rate, reflection coefficient, endothelial uptake clearance, and FcRn concentration) were optimized based on the pharmacokinetic profiles of mAbs with various pI values in wild type and FcRn-deficient (beta-2-microglobulin knockout [KO]) mice. Simulations using the PBPK model developed in this study showed a positive correlation between pI, CL and Vdss observed in wild-type mice. Therefore, this model successfully characterized our hypothetical mechanism that an electrostatic positive interaction between mAbs and the endothelial membrane enhances FcRn-mediated transcytosis of mAbs, resulting in large Vdss. We sought to determine the right contribution of the two pathways of antibody distribution to the interstitial space and established a new model that could effectively capture the effect of pI on FcRn-mediated distribution of mAbs in the body.


Subject(s)
Antibodies, Monoclonal , Models, Biological , Mice , Animals , Antibodies, Monoclonal/pharmacokinetics , Biological Transport , Kinetics , Mice, Knockout , Receptors, Fc/genetics , Receptors, Fc/metabolism , Histocompatibility Antigens Class I/metabolism
15.
Antimicrob Agents Chemother ; 67(11): e0074423, 2023 11 15.
Article in English | MEDLINE | ID: mdl-37874301

ABSTRACT

Although we previously reported that some meningococcal isolates in Japan were resistant to penicillin (PCG) and ciprofloxacin (CIP), the antibiotic susceptibilities of Neisseria meningitidis isolates obtained in Japan remained unclear. In the present study, 290 N. meningitidis isolates in Japan between 2003 and 2020 were examined for the sensitivities to eight antibiotics (azithromycin, ceftriaxone, ciprofloxacin, chloramphenicol, meropenem, minocycline, penicillin, and rifampicin). All isolates were susceptible to chloramphenicol, ceftriaxone, meropenem, minocycline, and rifampicin while two were resistant to azithromycin. Penicillin- and ciprofloxacin-resistant and -intermediate isolates (PCGR, CIPR, PCGI and CIPI, respectively) were also identified. Based on our previous findings from whole genome sequence analysis, approximately 40% of PCGI were associated with ST-11026 and cc2057 meningococci, both of which were unique to Japan. Moreover, the majority of ST-11026 meningococci were CIPR or CIPI. Sensitivities to PCG and CIP were closely associated with genetic features, which indicated that, at least for Japanese meningococcal isolates, PCGR/I or CIPI/R would be less likely to be horizontally conferred from other neisserial genomes by transferring of the genes responsible (penA and gyrA genes, respectively), but rather that ancestral N. meningitidis strains conferring PCGR/I or CIPI/R phenotypes clonally disseminated in Japan.


Subject(s)
Ciprofloxacin , Neisseria meningitidis , Ciprofloxacin/pharmacology , Neisseria meningitidis/genetics , Penicillins/pharmacology , Ceftriaxone/pharmacology , Japan , Rifampin , Azithromycin , Meropenem , Minocycline , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Chloramphenicol
16.
Int J Clin Oncol ; 28(12): 1573-1584, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37874429

ABSTRACT

Locally advanced and metastatic urothelial carcinoma (UC) remains a challenging malignancy, though several novel therapeutic drugs have been developed in recent years. Over the past decade, immune checkpoint inhibitors (ICI) have shifted the paradigm of therapeutic strategies for UC; however, only a limited number of patients respond to ICI. Since radiotherapy (RT) is widely known to induce systemic immune activation, it may boost the efficacy of ICI. Conversely, RT also causes exhaustion of cytotoxic T cells, and the activation and recruitment of immunosuppressive cells; ICI may help overcome these immunosuppressive effects. Therefore, the combination of ICI and RT has attracted attention in recent years. The therapeutic benefits of this combination therapy and its optimal regimen have not yet been determined through prospective studies. Therefore, this review article aimed to provide an overview of the current preclinical and clinical studies that illustrate the underlying mechanisms and explore the optimization of the RT regimen along with the ICI and RT combination sequence. We also analyzed ongoing prospective studies on ICI and RT combination therapies for metastatic UC. We noted that the tumor response to ICI and RT combination seemingly differs among cancer types. Thus, our findings highlight the need for well-designed prospective trials to determine the optimal combination of ICI and RT for locally advanced and metastatic UC.


Subject(s)
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Humans , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/radiotherapy , Carcinoma, Transitional Cell/pathology , Immune Checkpoint Inhibitors/therapeutic use , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/radiotherapy , Urinary Bladder Neoplasms/pathology , Prospective Studies , Combined Modality Therapy
17.
Front Microbiol ; 14: 1209195, 2023.
Article in English | MEDLINE | ID: mdl-37664110

ABSTRACT

Introduction: The prevalence of Guiana extended-spectrum (GES)-type carbapenemase producers is increasing worldwide, and hospital water environments are considered as potential reservoirs. However, the genetic features underlying this resistance are not yet fully understood. This study aimed to characterize blaGES-encoding plasmids from a single-hospital sewage sample in Japan. Methods: Carbapenemase producers were screened using carbapenemase-selective agar and polymerase chain reaction. Whole-genome sequencing analyzes were performed on the carbapenemase-producing isolates. Results: Eleven gram-negative bacteria (four Enterobacter spp., three Klebsiella spp., three Aeromonas spp., and one Serratia spp.) with blaGES-24 (n = 6), blaGES-6 (n = 4), and blaGES-5 (n = 1) were isolated from the sewage sample. Five blaGES-24 and a blaGES-5 were localized in IncP-6 plasmids, whereas three blaGES-6 plasmids were localized in IncC plasmids with IncF-like regions. The remaining blaGES-6 and blaGES-24 were, respectively, localized on IncFIB-containing plasmids with IncF-like regions and a plasmid with an IncW-like replication protein. The IncP-6 and IncW-like plasmids had a close genetic relationship with plasmids from Japan, whereas the IncC/IncF-like and IncFIB/IncF-like plasmids were closely related to those from the United States and Europe. All blaGES genes were located on the class 1 integron cassette of the Tn3 transposon-related region, and the IncC/IncF-like plasmid carried two copies of the integron cassette. Eight of the eleven blaGES-encoding plasmids contained toxin-antitoxin system genes. Discussion: The findings on the plasmids and the novel genetic content from a single wastewater sample extend our understanding regarding the diversity of resistance and the associated spread of blaGES, suggesting their high adaptability to hospital effluents. These findings highlight the need for the continuous monitoring of environmental GES-type carbapenemase producers to control their dissemination.

19.
J Infect Chemother ; 29(5): 562-564, 2023 May.
Article in English | MEDLINE | ID: mdl-36758676

ABSTRACT

Meningococcal chemoprophylaxis for people in close contact with patients with invasive meningococcal disease (IMD) is necessary for preventing the spread of Neisseria meningitidis. Ciprofloxacin (CIP) is commonly used to treat IMD. However, CIP-resistant N. meningitidis isolates have rapidly evolved worldwide; therefore, rapid and accurate detection of CIP-resistant N. meningitidis is essential. We developed a mismatch amplification mutation assay for identifying gyrA substitutions T91I and D95Y, associated with reduced CIP susceptibility, using two primer sets to detect these variants. Comparison with gyrA sequencing data showed complete congruency. This method enables reliable detection of CIP-resistant N. meningitidis, thus leading to efficient management and control of IMD infections.


Subject(s)
Meningococcal Infections , Neisseria meningitidis , Humans , Ciprofloxacin/pharmacology , Ciprofloxacin/therapeutic use , Neisseria meningitidis/genetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Drug Resistance, Bacterial/genetics , Meningococcal Infections/diagnosis , Meningococcal Infections/drug therapy , Mutation
20.
Exp Anim ; 72(2): 193-198, 2023 May 17.
Article in English | MEDLINE | ID: mdl-36288979

ABSTRACT

To understand effects of aging and reproductive history in the bones of common marmosets (Callithrix jacchus), mandibles from 79 males and 66 females were analyzed. Dry bone specimen was prepared from dissected mandible, and analyzed using a dual-energy x-ray absorptiometry (DXA) measurement system in terms of bone weight (BnW), bone area (AREA), bone mineral content (BMC), bone mineral density (BMD, ratio of BMC to AREA) and bone mineral ratio (BMR, ratio of BMC to BnW). The mandible bones became porous and thicker with age. The age-related changes in BnW, AREA and BMC showed inflection points at around 1.5-2 Y and 13-15 Y. The period before 1.5-2 Y corresponds to the growth phase, the period between the inflection points is the aging phase, followed by senescence after the second inflection point. BMD increased until 1.5-2 Y and gradually decreased thereafter in males, with a more dramatic decrease in females, probably because of pregnancy and lactation. BMR was stable after reaching its peak by 1 Y, unlike the other parameters we analyzed. BMD of parous female tended to be lower than that of nulliparous female aged 2-5 Y. This study identified some of the particular effects of aging and reproductive history on characteristics of mandible bones in common marmoset.


Subject(s)
Callithrix , Reproductive History , Male , Pregnancy , Female , Animals , Bone Density , Aging , Mandible
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