Osaka City University Hospital Research Articles

A Case of Bariatric Surgery for a Japanese Kidney Transplant Recipient With Diabetes Mellitus: A Case Report

The patient, a 54-year-old woman, underwent a living donor kidney transplant at Osaka City University Hospital 7 years before the bariatric surgery. Her comorbidities were diabetes, sleep apnea, and severe obesity (weight 103 kg, body mass index [BMI] 36 kg/m2), and her diabetes was poorly controlled with an HbA1c of 8.5%. On admission, she weighed 99 kg, BMI was 34 kg/m2, Serum creatinine (S-Cre) was 1.54 mg/dL, and HbA1c was 7.1%. A laparoscopic sleeve gastrectomy was performed, and her weight decreased without complications during the perioperative period. She was discharged on postoperative day 28. Two months after surgery, her weight was 87 kg, BMI 30 kg/m2, S-Cre 1.34 mg/dL, HbA1c 6.7 %, renal function improved, urine protein decreased, and insulin dosage decreased dramatically. We report this valuable case because there are no reports of bariatric surgery in Japanese renal transplant recipients.

Impact of a circular powered stapler on preventing anastomotic leakage in patients with left-sided colorectal cancer: a retrospective study

BackgroundThe powered circular stapler, which was developed with the aim of providing reliable and reproducible anastomosis, provides complete anastomosis, resulting in a reduced risk of anastomotic leakage. The aim of this study was to compare the incidence of anastomotic leakage between a conventional manual circular stapler (MCS) and the ECHELON CIRCULAR™ Powered Stapler (ECPS) in patients with left-sided colorectal cancer who underwent anastomosis with the double stapling technique.MethodsA total of 187 patients with left-sided colorectal cancer who underwent anastomosis with the double stapling technique with a conventional MCS or the ECPS during surgery at Osaka City University Hospital between January 2016 and July 2022 were enrolled in this study.ResultsThe incidence of anastomotic leakage in the ECPS group was significantly lower than that in the MCS group (4.4% versus 14.3%, p = 0.048). Furthermore, even after propensity score matching, an association was found between the use of the ECPS and a reduced incidence of anastomotic leakage.ConclusionThe ECPS has the potential to help reduce the rate of anastomotic leakage in left-sided colorectal surgery.

Efficacy of the polyglycolic acid sheet for preventing anastomotic leakage in double-stapling technique anastomosis for left-sided colon or rectal cancer surgery: a propensity score-matched study

BackgroundTo prevent anastomotic leakage in patients with left-sided colorectal cancer who underwent double-stapling technique (DST) anastomosis, we investigated a new method: DST anastomosis with a polyglycolic acid (PGA) sheet. This procedure has been shown to have the potential to decrease the rate of anastomotic leakage. However, due to the small number of cases enrolled in our previous study, it was not possible to compare the outcomes of the new and conventional procedures. The aim of this study was to evaluate the effect of the PGA sheet on preventing anastomotic leakage in patients with left-sided colorectal cancer who underwent DST anastomosis by retrospectively comparing the anastomotic leakage rate between the PGA sheet and conventional groups.MethodsA total of 356 patients with left-sided colorectal cancer who underwent DST anastomosis during surgery at Osaka City University Hospital between January 2016 and April 2022 were enrolled in this study. Propensity score matching was performed to reduce the confounding effects secondary to imbalances in the use of PGA sheets.ResultsThe PGA sheet was used in 43 cases (PGA sheet group) and it was not used in 313 cases (conventional group). After propensity score matching, the incidence of anastomotic leakage in the PGA sheet group was significantly lower than that in the conventional group.ConclusionDST anastomosis with PGA sheet, which is easy to perform, contributes to the reduction of anastomotic leakage rate by increasing the strength of the anastomotic site.

Impact of the COVID-19 pandemic on bone and soft tissue tumor treatment: A single-institution study.

The spread of coronavirus disease 2019 (COVID-19) has caused a great deal of damage to daily medical care. We investigated the impact of the COVID-19 pandemic on bone and soft tissue tumor treatment at our hospital. We conducted a retrospective comparative study of two groups of patients at Osaka City University Hospital during the period of increasing COVID-19 infections (February-December 2020, group C) and the same period the previous year (February- December 2019, group NC). Clinical data, including patient's age, gender, type of tumor, neoplasms, number of surgical cases for inpatients and outpatients, operation time, use of implants, length of hospital stay, inpatient hospital costs, number of inpatients receiving anticancer drugs, and postoperative complications in these two groups were retrospectively evaluated. The number of cases of malignant bone and soft tissue tumors that were resected during hospitalization was predominantly higher in group C than in group NC (P = 0.01). There were no significant differences in operation time, use of implants, and postoperative complications between group C and group NC, but there were significant differences in the length of hospital stay and hospital costs (P<0.001). The COVID-19 pandemic has been recognized throughout the world to have adverse effects in a variety of areas. It had a negative impact on hospital costs and the length of hospital stay in the field of bone and soft tissue tumor treatment.

Neutrophil-to-lymphocyte ratio may predict clinical relapse in ulcerative colitis patients with mucosal healing.

Endoscopic mucosal healing (MH) is an important treatment goal for patients with ulcerative colitis (UC). The neutrophil-to-lymphocyte ratio (NLR) reflects systemic inflammation and has been reported to be a useful predictive marker for UC. This study aimed to evaluate the clinical utility of the NLR for predicting clinical relapse in UC patients with MH. We retrospectively enrolled patients with UC who underwent colonoscopy at the Osaka City University Hospital between January 2010 and December 2010, whose Mayo Endoscopic Subscore was 0 or 1. The correlation between the incidence of relapse and demographic factors, including the NLR, was analyzed. We included 129 patients in the present study. The median NLR at the time of endoscopy was 1.98, and differences in the high NLR group and the low NLR group were compared. During a median follow-up period of 46.4 months, 58 patients (45.0%) experienced relapse. The cumulative relapse-free rate was significantly higher in the low NLR group than in the high NLR group (P = 0.03, log-rank test). Multivariate analysis identified high NLR as an independent prognostic factor for clinical relapse (hazard ratio, 1.74; 95% confidence interval, 1.02-2.98; P = 0.04). NLR is a novel and useful predictor of clinical relapse in UC patients with MH, and it can potentially be a strong indicator to determine the appropriate treatment strategy and decision-making in clinical practice.

Histology of the tricuspid valve annulus and right atrioventricular muscle distance.

OBJECTIVESHistologically, the mitral valve annulus comprises a collection of collagen fibres. However, the existence of collagen fibres in the tricuspid valve annulus has not been elucidated. Our goal was to clarify the histology of the tricuspid annulus.METHODSFifty human hearts without heart disease that were autopsied at Osaka City University Hospital between January 2009 and December 2017 were examined. The tricuspid valve was sectioned at 12 sites around the annulus, and the atrioventricular junction distance was measured.RESULTSNone of the tricuspid valve annulus samples had a continuous aggregation of collagen fibres that could be called an annulus. The interventricular space between the right atria and ventricles was composed of adipose tissue only on the anterosuperior and inferior sides, and no adipose tissue was found on the septal side. Comparing the atrioventricular muscle distance of the anterosuperior and inferior sides, the distance at the inferior side was statistically significantly larger than that of the anterosuperior side in 47 cases (P < 0.0001).CONCLUSIONSThere was no continuous circumferential aggregation of collagen fibres in the right atrioventricular junction. The distance between the right atrial and ventricular myocardium was greater at the inferior side than that at the anterosuperior side, which might lead to more inferior annular dilation versus anterosuperior dilation. These anatomical features will be fundamental for future discussions of the suturing method used in prosthetic ring annuloplasty for tricuspid regurgitation.

A retrospective study on optimal number of cycles of the first-line platinum-based chemotherapy for metastatic urothelial carcinoma

Recently, switch maintenance with avelumab has been approved for the treatment of advanced or metastatic urothelial carcinoma (UC), with no progression after four to six cycles of first-line platinum-based chemotherapy. However, the optimal number of cycles of platinum-based chemotherapy has not been determined. To analyze the clinical characteristics of patients with advanced UC who were treated with platinum-based chemotherapy and investigate the association between the number of cycles of the treatment and the patients' overall survival. A total of 124 patients with advanced UC who were treated with first-line platinum-based chemotherapy at Osaka City University Hospital between April 2009 and January 2020 were retrospectively reviewed. Of the 124 patients, clinical information regarding overall survival was available for 115 patients. The median age was 72 years (range, 43-95 years). Only 59 patients (51.3 %) were treated with gemcitabine and cisplatin, and 52 patients (45.2 %) were treated with gemcitabine and carboplatin. The median number of cycles was three (1-8), and the percentage of patients who discontinued chemotherapy due to progressive disease was 80.3%, 64.0%, and 86.4% in those receiving one to three, four, and five or more cycles, respectively. Moreover, no difference in overall survival was observed between patients who received four cycles and those who received five or more cycles at both univariate and multivariate levels. The present study shows that five or more cycles of first-line platinum-based chemotherapy did not prolong overall survival compared with four cycles, suggesting that four cycles of chemotherapy might be sufficient, considering the new treatment strategy involving switch maintenance with avelumab.

Associations Between Chronic Irritability and Sensory Processing Difficulties in Children and Adolescents.

Irritability is one of the most common reasons for which children and adolescents are referred for psychiatric evaluation and care. However, clinical irritability is difficult to define; thus, its prevalence varies widely. Chronic irritability may be associated with sensory processing difficulties (SPD), but little is known about the relationship between these two factors in clinical populations. In this study, we examined the prevalence of chronic irritability and its association with SPD in 166 children aged 5–16 years who were referred to the psychiatric outpatient clinic of the Osaka City University Hospital. Chronic irritability and parent-reported scores for the Short Sensory Profile, Infant Behavior Checklist-Revised, Child Behavior Checklist, and Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children (Present and Lifetime version) questionnaires were used for assessment. A total of 22 children (13.2%) presented with chronic irritability (i.e., the irritability group) and were more likely to have oppositional defiant disorder, externalizing problems, and attention issues than those without chronic irritability (i.e., the control group). SPD were reported in eight (36%) patients in the irritability group and in 21 (15%) in the control group (p = 0.029). Moreover, compared to the control group, the irritability group showed a significant difference in almost all items of the Short Sensory Profile. Chronic irritability was associated with more severe overall SPD, even after adjusting for possible confounding factors (internalizing and externalizing problems, age, sex, and low income). We provide evidence to support our hypothesis that chronic irritability is associated with SPD in children and adolescents. Therefore, SPD should be assessed to provide appropriate interventions in children and adolescents with chronic irritability.

Development and validation of a deep learning model for detection of breast cancers in mammography from multi-institutional datasets.

ObjectivesThe objective of this study was to develop and validate a state-of-the-art, deep learning (DL)-based model for detecting breast cancers on mammography.MethodsMammograms in a hospital development dataset, a hospital test dataset, and a clinic test dataset were retrospectively collected from January 2006 through December 2017 in Osaka City University Hospital and Medcity21 Clinic. The hospital development dataset and a publicly available digital database for screening mammography (DDSM) dataset were used to train and to validate the RetinaNet, one type of DL-based model, with five-fold cross-validation. The model’s sensitivity and mean false positive indications per image (mFPI) and partial area under the curve (AUC) with 1.0 mFPI for both test datasets were externally assessed with the test datasets.ResultsThe hospital development dataset, hospital test dataset, clinic test dataset, and DDSM development dataset included a total of 3179 images (1448 malignant images), 491 images (225 malignant images), 2821 images (37 malignant images), and 1457 malignant images, respectively. The proposed model detected all cancers with a 0.45–0.47 mFPI and had partial AUCs of 0.93 in both test datasets.ConclusionsThe DL-based model developed for this study was able to detect all breast cancers with a very low mFPI. Our DL-based model achieved the highest performance to date, which might lead to improved diagnosis for breast cancer.

Effect of the Coronavirus Disease 2019 Lockdown on Lifestyle Factors in Japanese Patients with Inflammatory Bowel Disease.

Objective To examine the effect of the coronavirus disease 2019 (COVID-19) lockdown on lifestyle factors and psychological stress in patients with inflammatory bowel disease (IBD). Methods A retrospective study was conducted on patients with IBD in Japan 2 months after the initiation of the first state of emergency (June 16 to August 21, 2020). A self-reported questionnaire was used to collect data, and lifestyle factors and psychological stress levels before and after the state of emergency were compared. Patients Patients with IBD who were followed up regularly at Osaka City University Hospital from June 16 to August 21, 2020, were included and were classified into elderly (≥65 years old) and non-elderly groups (<65 years old). Results The study sample comprised 451 responders (241, ulcerative colitis; 210, Crohn's disease; 0, COVID-19). The sleep duration increased, whereas the exercise, working, and walking durations decreased during the COVID-19 lockdown. The proportion of patients with psychological stress due to COVID-19, those with an inability to exercise, and those staying indoors increased significantly during COVID-19 lockdown. Lifestyle factors changed more markedly in non-elderly patients, those who were more stressed due to COVID-19, those with the inability to exercise, and those staying indoors during COVID-19 lockdown. Among elderly patients, no significant changes were identified in stress-causing factors. Conclusion The COVID-19 lockdown affected lifestyle factors and psychological stress in patients with IBD, particularly non-elderly patients. These findings may be helpful in suggesting favorable lifestyle changes for patients with IBD.

Long-term use of foscarnet is associated with an increased incidence of acute kidney injury in hematopoietic stem cell transplant patients: A retrospective observational study.

Foscarnet is an important drug for the treatment of cytomegalovirus infection in patients undergoing hematopoietic stem cell transplantation (HSCT). Foscarnet is often discontinued because of the development of acute kidney injury (AKI). Thus, the identification of factors leading to the development of AKI is beneficial. This study aimed to investigate the incidence of AKI and the factors influencing AKI development in HSCT patients treated with foscarnet. This was a retrospective observational study. Patients who underwent HSCT and received foscarnet at the Department of Hematology, Osaka City University Hospital, were identified from medical records. The patients were classified into AKI and non-AKI groups, and the risk factors associated with AKI were evaluated. For continuous variables, receiver-operating characteristic (ROC) curve analysis was used to calculate the optimal cutoff value. Thirty-five patients (47 cases) were assigned to the AKI (51.1%, 24/47) and non-AKI groups (48.9%, 23/47). The AKI group had a significantly longer foscarnet administration period than the non-AKI group (p=0.049). The appropriate cutoff value for the foscarnet administration period using the ROC curve was 27days. The incidence of AKI was significantly higher in cases who received foscarnet for more than 27days (11/14, 78.6%) compared to those who received less than 27days (13/33, 39.4%) (odds ratio: 5.64, 95% confidence interval 1.32-24.2, p=0.024). The incidence of AKI was 51.1% in HSCT patients treated with foscarnet, and foscarnet administration for more than 27days may be associated with the incidence of AKI.

Body Mass Index of Elderly Patients with Normal Renal Function as a Determining Factor for Initial Vancomycin Regimen Designing

Introduction: Currently, the use of actual body weight is recommended for dosing in vancomycin regimen designs, and it is important to perform therapeutic drug monitoring for efficacy and safety. However, the method to determine the appropriate vancomycin regimen for underweight or obese patients remains controversial. The aim of this study was to evaluate the impact of body mass index (BMI) on the relationship among vancomycin doses, trough concentration, and area under the curve (AUC). In addition, we identified the group of patients who were potentially more affected by BMI and evaluated the optimal dosing regimen to achieve the target AUC. Methods: We retrospectively collected data from 462 patients who received vancomycin at the Osaka City University Hospital between January 2013 and September 2019. Patients were classified by their BMI group (underweight <18.5, normal weight 18.5–24.9, and obese ≥25.0 kg/m2). We assessed the association between vancomycin dose versus trough concentration or AUC as well as dose-adjusted trough concentration and AUC in each BMI subgroup to determine the doses for achieving the target AUC. Results: The dose-adjusted trough concentration and AUC in elderly patients with normal renal function appeared to increase significantly with an increase in BMI (p < 0.05). Vancomycin doses that enabled the achievement of AUC400 in elderly patients with normal renal function decreased with increasing BMI: 17.7, 15.8, and 12.9 mg/kg per time in the underweight, normal weight, and obesity groups, respectively (p < 0.05). Conclusion: Elderly patients with normal renal function were the most affected by BMI on vancomycin trough concentration and AUC. The vancomycin regimen design in these patients should be adjusted carefully, not only based on the patient’s renal function but also based on BMI.

Phase III, international, multicentre, double-blind, dose increment, parallel-arm, randomised controlled trial of duloxetine versus pregabalin for opioid-unresponsive neuropathic cancer pain: a JORTC-PAL16 trial protocol

IntroductionManagement of neuropathic cancer pain (NCP) refractory to regular opioids remains an important challenge. The efficacy of pregabalin for NCP except chemotherapy-induced peripheral neuropathy (CIPN) has already been confirmed in...

Hyperpolypharmacy and Frailty in Kidney Transplant Recipients

Kidney transplant recipients (KTRs) take multiple medications including immunosuppressants every day. Although polypharmacy is associated with frailty, the situation remains unknown in KTRs. The aim of the present study is to investigate the association between hyperpolypharmacy and frailty in KTRs. This study was a single-center, cross-sectional investigation carried out on KTRs between August 2018 and February 2019 at Osaka City University Hospital. Frailty was evaluated using the Kihon Checklist (KCL). The number of medications was determined from the regular medicines the participants took by mouth every day. Hyperpolypharmacy was defined as 10 or more medications. Statistical analyses were performed using multivariable logistic regression analyses and multivariable linear regression analyses. Of 211 KTRs enrolled in this study, the mean (SD) number of medicines taken orally regularly was 9.4 (3.4), and hyperpolypharmacy participants accounted for 41%. Hyperpolypharmacy was associated with both the total KCL score (odds ratio, 1.13; P=.016) and being frail compared with being robust (odds ratio, 5.70; P=.007) after adjustments for age, sex, and body mass index. The number of medications was associated with both the total KCL score (β=0.20; P < .001) and being frail compared with being robust (β=2.51; P < .001) after adjustments for age, sex, body mass index, dialysis vintage, time after transplant, serum albumin, and estimated glomerular filtration rate. The optimal cutoff value for the number of medications to detect frailty was 12 (area under the curve, 0.81). In KTRs, hyperpolypharmacy was prevalent and was associated with frailty.

Maximum 11C-methionine PET uptake as a prognostic imaging biomarker for newly diagnosed and untreated astrocytic glioma

This study aimed whether the uptake of amino tracer positron emission tomography (PET) can be used as an additional imaging biomarker to estimate the prognosis of glioma. Participants comprised 56 adult patients with newly diagnosed and untreated World Health Organization (WHO) grade II–IV astrocytic glioma who underwent surgical excision and were evaluated by 11C-methionine PET prior to the surgical excision at Osaka City University Hospital from July 2011 to March 2018. Clinical and imaging studies were retrospectively reviewed based on medical records at our institution. Preoperative Karnofsky Performance Status (KPS) only influenced progression-free survival (hazard ratio [HR] 0.20; 95% confidence interval [CI] 0.10–0.41, p < 0.0001), whereas histology (anaplastic astrocytoma: HR 5.30, 95% CI 1.23–22.8, p = 0.025; glioblastoma: HR 11.52, 95% CI 2.27–58.47, p = 0.0032), preoperative KPS ≥ 80 (HR 0.23, 95% CI 0.09–0.62, p = 0.004), maximum lesion-to-contralateral normal brain tissue (LN max) ≥ 4.03 (HR 0.24, 95% CI 0.08–0.71, p = 0.01), and isocitrate dehydrogenase (IDH) status (HR 14.06, 95% CI 1.81–109.2, p = 0.011) were factors influencing overall survival (OS) in multivariate Cox regression. OS was shorter in patients with LN max ≥ 4.03 (29.3 months) than in patients with LN max < 4.03 (not reached; p = 0.03). OS differed significantly between patients with IDH mutant/LN max < 4.03 and patients with IDH mutant/LN max ≥ 4.03. LN max using 11C-methionine PET may be used in prognostic markers for newly identified and untreated WHO grade II–IV astrocytic glioma.

The Change in Muscle Mass Among Kidney Transplant Recipients: A Prospective Cohort Study

Recovery of renal function after transplantation leads to improved uremic conditions, increased physical activity, and liberation from severe dietary restrictions. Consequently, the muscle mass of kidney transplant recipients increases for several years after their transplant. However, the change in muscle mass and its associated factors among these patients remain largely unknown. Herein, we carried out a prospective cohort study with 1-year follow-up to investigate how muscle mass changes and to identify its risk factors among kidney transplant recipients. We performed a single-center, 1-year, prospective, observational cohort study from August 2017 to February 2019 at Osaka City University Hospital in Japan. The skeletal muscle mass index (SMI) was measured by bioelectrical impedance analysis. The risk factors related to the change in muscle mass were analyzed using multivariate linear regression models of age, sex, body mass index (BMI), dialysis vintage, transplant vintage, diabetes mellitus, hemoglobin, C-reactive protein, estimated glomerular filtration rate, and SMI at baseline. A total of 180 kidney transplant recipients were enrolled in the present study. The median age was 55 years, and the median transplant vintage was 78 months. The median rate of change in SMI was +2.07%, and SMI increased in 118 (66%) patients during the 1-year follow-up. By multivariate analysis, the change in SMI at 1-year follow-up was independently associated with age (P=0.017) and BMI (P=.023). SMI increased in most of the kidney transplant recipients, and age and BMI might be the risk factors for this change in muscle mass among these patients.

Age at menarche in Japanese patients with type 1 diabetes mellitus: a look at changes since 1960s.

Menarche is delayed in patients with type 1 diabetic mellitus (T1DM) compared to non-diabetics. The purpose of this survey study was to define the age of onset of menarche in Japanese patients with T1DM, as well the secular trends in menarcheal age across the period of 1976-2020 and determine the effects of T1DM and disease management on that age. The study subjects (n = 155) were recruited from among Japanese T1DM patients who visited the outpatient clinic of the Department of Pediatrics, Osaka City University Hospital. The study subjects experienced menarche during 1976-2020. They were divided into the menarche-post-T1DM group (n = 117) and the menarche-pre-T1DM group (n = 38), in whom menarche occurred after or before the diagnosis of T1DM, respectively. The time of birth was also stratified into five decade/time bins extending from 1960s to 2000s. The subjects filled a questionnaire on menarche. Other clinical information was obtained from the medical records. The median age at menarche was 12.5 years (11.3-13.4) (25th-75th percentile) for the menarche-post-T1DM group and 11.8 years (10.9-13.0) for the menarche-pre-T1DM group (p = 0.024). Menarche occurred at a significantly younger age in recent years in the menarche-post-T1DM group (r = -0.209, p = 0.023), but no such trend was found in the control group. Analysis of data of subjects born after 1990 still showed significant delay associated with T1DM [post-T1DM group: 12.3 years (11.3-13.2), pre-T1DM group: 11.8 years (11.0-12.2), p = 0.045]. The results suggest that recent advances in insulin therapy seem to improve metabolism under T1DM but might have not enough impact on menarche in Japanese girls.

Relationship Between Bedside Ketone Levels and Time to Resolution of Diabetic Ketoacidosis: A Retrospective Cohort Study

IntroductionThere is no information on the factors that influence the time required to induce resolution of diabetic ketoacidosis (DKA). New methods are currently available for bedside measurement of serum 3-hydroxybutyrate (3HB). The aim of this study was to determine the relationship between serum 3HB and the time to DKA resolution.MethodsWe reviewed the medical records of patients with type 1 diabetes (T1D) and a history of DKA who were admitted to the Department of Pediatrics, Osaka City University Hospital, between November 2008 and October 2018. DKA resolution was defined as 3HB below 1.0 mmol/L as measured by a bedside ketone meter.ResultsData of 52 T1D-DKA episodes were analyzed (median age, 8.0 years; 20 male patients; 32 female patients; new T1D diagnosis, n = 13; established diagnosis, n = 39). In all cases, correction of serum 3HB was an important aspect of T1D management. The median time to DKA resolution (defined as the time from the start of insulin infusion until the fall of 3HB level to below 1.0 mmol/L) was 11 and 10 h in new and established T1D cases, respectively. 3HB on admission and the required insulin infusion dose per body weight, but not blood pH level on admission, correlated with time to DKA resolution. There was no relationship between blood pH level and 3HB on admission.ConclusionsOur results showed that DKA resolution could be achieved within 10–11 h when DKA treatment is guided by bedside 3HB monitoring without any severe complications. Blood 3HB level is a potentially suitable marker for the severity and resolution of DKA.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-021-01167-y.

Genomic characterization of triple-carbapenemase-producing Acinetobacter baumannii.

ObjectivesTo characterize Acinetobacter baumannii OCU_Ac16a, a clinical isolate co-harbouring three acquired carbapenemase genes, blaNDM-1, blaTMB-1, and blaOXA-58, and assess the clinical significance of so-called multiple-carbapenemase producers.MethodsOCU_Ac16a and its close relative, OCU_Ac16b, which lacks the blaNDM-1, were isolated from sputum cultures of a patient at Osaka City University Hospital. We subjected these strains to whole-genome analysis, particularly focusing on the genetic context of each carbapenemase gene. The transmissibility and functionality of each carbapenemase gene were analysed by conjugation and transformation experiments and antimicrobial susceptibility tests.Results bla TMB-1 was located in a class 1 integron on the chromosome, whereas blaNDM-1 and blaOXA-58 were found on plasmids named pOCU_Ac16a_2 and pOCU_Ac16a_3, respectively. pOCU_Ac16a_2 (which exhibited highly efficient self-transmissibility) and pOCU_Ac16a_3 (which did not show transmissibility but could be introduced into another A. baumannii strain via electroporation) could both confer carbapenem resistance (MICs ≥512 and ≥32 mg/L, respectively) on the recipient strain. The functionality of blaTMB-1 was evident from the high resistance of OCU_Ac16b to ceftazidime and cefepime (MICs ≥256 and 48 mg/L, respectively), and the high resistance of OCU_Ac16a to cefiderocol (MIC 32 mg/L) could be explained by the additive effect of blaNDM-1 and blaTMB-1.ConclusionsOur data revealed the genomic organization of OCU_Ac16a and demonstrated that all the carbapenemase genes are functional, each contributing to the extremely high broad-spectrum resistance of OCU_Ac16a to β-lactams. As multiple-carbapenemase producers can be serious health threats as drug-resistant pathogens and disseminators of carbapenemase genes, close attention should be paid to their emergence.

Clinical significance of coexisting histological diffuse type in stage II/III gastric cancer.

Since 1965, the Laurén classification has been used most commonly for gastric adenocarcinoma, with two main types: intestinal type and diffuse type. Signet ring cell carcinoma (Sig) and non-solid poorly differentiated adenocarcinoma (Por2) are the histological forms of diffuse type that are often found in advanced tumors, and they seem to be associated with a poor prognosis. S-1-based adjuvant chemotherapy for patients with stage II/III gastric cancer has generally been accepted in Japan, but histological type does not alter treatment strategy. The aim of the present study was to investigate the prognostic impact of the histopathological mixture of Sig and Por2 in patients with stage II/III gastric cancer treated with S-1 adjuvant chemotherapy. The clinicopathological data of 968 patients with gastric carcinoma who underwent gastrectomy between 2007 and 2016 at Osaka City University Hospital were retrospectively analyzed. In the present study, tumors containing Sig or Por2 were classified as diffuse type, and those not containing them were classified as intestinal type. There were 307 cases of diffuse type and 661 cases of intestinal type. Diffuse type included 189 cases with Sig. A pathological diagnosis of Sig was an independent risk factor for peritoneal recurrence in patients with stage II/III gastric cancer. Patients with diffuse type had a worse overall survival rate than those with intestinal type at stage III gastric cancer. Among the patients who received S-1 adjuvant chemotherapy, the prognosis of patients with stage III gastric cancer with Sig but not Por2 was significantly worse compared with that of patients with intestinal type. Therefore, the present study revealed that the coexistence of Sig in the primary tumor was associated with a poor prognosis in patients with stage III gastric cancer. The current findings suggested that, since mixed Sig gastric cancer had a high risk of peritoneal recurrence even if adjuvant chemotherapy was performed, the pathological diagnosis should be considered when determining the therapeutic strategy for adjuvant chemotherapy in patients with stage III gastric cancer.