A prospective compound screening contest identified broader inhibitors for Sirtuin 1.

Potential inhibitors of a target biomolecule, NAD-dependent deacetylase Sirtuin 1, were identified by a contest-based approach, in which participants were asked to propose a prioritized list of 400 compounds from a designated compound library containing 2.5 million compounds using in silico methods and scoring. Our aim was to identify target enzyme inhibitors and to benchmark computer-aided drug discovery methods under the same experimental conditions. Collecting compound lists derived from various methods is advantageous for aggregating compounds with structurally diversified properties compared with the use of a single method. The inhibitory action on Sirtuin 1 of approximately half of the proposed compounds was experimentally accessed. Ultimately, seven structurally diverse compounds were identified.

Performance of laboratory tests for detection for Clostridioides difficile: A multicenter prospective study in Japan.

BACKGROUND: The optimal and practical laboratory diagnostic approach for detection of Clostridioides difficile to aid in the diagnosis of C. difficile infection (CDI) is controversial. A two-step algorithm with initial detection of glutamate dehydrogenase (GDH) or nucleic acid amplification test (NAAT) alone are recommended as a predominant method for C. difficile detection in developed countries. The aim of this study was to compare the performance of enzyme immunoassays (EIA) detecting toxins A and B, NAAT detecting the toxin B gene, and GDH compared to toxigenic culture (TC) for C. difficile as the gold standard, in patients prospectively and actively assessed with clinically significant diarrhea in 12 medical facilities in Japan. METHODS: A total of 650 stool specimens were collected from 566 patients with at least three diarrheal bowel movements (Bristol stool grade 6-7) in the preceding 24 h. EIA and GDH were performed at each hospital, and NAAT and toxigenic C. difficile culture with enriched media were performed at the National Institute of Infectious Diseases. All C. difficile isolates recovered were analyzed by PCR-ribotyping. RESULTS: Compared to TC, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of EIA were 41%, 96%, 75% and 84%, respectively, and for NAAT were 74%, 98%, 91%, and 92%, respectively. In 439 specimens tested with GDH, the sensitivity, specificity, PPV, and NPV were 73%, 87%, 65%, and 91%, and for an algorithm (GDH plus toxin EIA, arbitrated by NAAT) were 71%, 96%, 85%, and 91%, respectively. Among 157 isolates recovered, 75% of isolates corresponded to one of PCR-ribotypes (RTs) 002, 014, 018/018", and 369; RT027 was not isolated. No clear differences in the sensitivities of any of EIA, NAAT and GDH for four predominant RTs were found. CONCLUSION: The analytical sensitivities of NAAT and GDH-algorithm to detect toxigenic C. difficile in this study were lower than most previous reports. This study also found low PPV of EIAs. The optimal method to detect C. difficile or its toxins to assist in the diagnosis of CDI needs further investigation.

[Perceptions toward Employment and Support Needs in Medical Institutions and Workplace among AYA Cancer Survivors].

We conducted a cross-sectional questionnaire study to explore perceptions of employment, job-related help-seeking behaviors at the time of cancer diagnosis, illness disclosure at the workplace, and support needs for continuous employment among adolescent and young adult cancer survivors. The mean age at the time of cancer diagnosis was 27.8(range, 15-37) years. For survivors in this age category, employment is the foundation for economic development and contributions to society. Approximately half of the participants sought job-related help from medical staff and employment experts. Approximately 90%of the participants disclosed their illness to their workplace, and most were given consideration for their situation. To ensure continuous employment, the participants required environmental improvement at the workplace rather than consultation services at hospitals. This study suggests the need to further investigate when and where certain support is required and to consider ways to improve support at both hospitals and workplaces.

Preferences Regarding End-of-Life Care Among Adolescents and Young Adults With Cancer: Results From a Comprehensive Multicenter Survey in Japan.

CONTEXT: Patient preferences influence end-of-life (EOL) care which patients receive. However, preferences regarding EOL care among adolescent and young adult (AYA) cancer population remain unclear. OBJECTIVES: The objective of the study was to evaluate preferences regarding EOL care among AYA cancer population. METHODS: We evaluated preferences regarding EOL care as a part of a comprehensive multicenter questionnaire study investigating the experience and needs of Japanese AYA cancer population. RESULTS: A total of 349 AYA cancer population (213 AYA cancer patients and 136 AYA cancer survivors) were evaluated. Eighty-six percent (296/344), 53% (180/338), 88% (301/341), and 61% (207/342) of participants with valid response preferred to have prognostic disclosure, receive palliative chemotherapy for incurable cancer with limited efficacy at the expense of considerable toxicity, actively use palliative care, and stay home at EOL, respectively. In multivariate analysis, the preference regarding prognostic disclosure was associated positively with no child status (odds ratio [OR] = 3.05, P = 0.003) and negatively with history of chemotherapy (OR = 0.23, P = 0.009), the preference regarding palliative chemotherapy for incurable cancer with limited efficacy at the expense of considerable toxicity was associated positively with status under active cancer treatment (OR = 1.74, P = 0.03), and the preference of staying home at EOL was positively associated with anxiety (OR = 1.72, P = 0.04). CONCLUSION: This study elucidated preferences regarding EOL care among Japanese AYA cancer population. These findings may help health care practitioners to have better understanding of preferences regarding EOL care among this population.

Clostridioides (Clostridium) difficile infection burden in Japan: A multicenter prospective study.

Clostridioides (Clostridium) difficile is the leading cause of healthcare-associated infectious diarrhea in the developed world. Retrospective studies have shown a lower incidence of C. difficile infection (CDI) in Japan than in Europe or North America. Prospective studies are needed to determine if this is due lack of testing for C. difficile or a true difference in CDI epidemiology. A prospective cohort study of CDI was conducted from May 2014 to May 2015 at 12 medical facilities (20 wards) in Japan. Patients with at least three diarrheal bowel movements (Bristol stool grade 6-7) in the preceding 24 h were enrolled. CDI was defined by positive result on enzyme immunoassay for toxins A/B, nucleic acid amplification test for the toxin B gene or toxigenic culture. C. difficile isolates were subjected to PCR-ribotyping (RT), slpA-sequence typing (slpA-ST), and antimicrobial susceptibility testing. The overall incidence of CDI was 7.4/10,000 patient-days (PD). The incidence was highest in the five ICU wards (22.2 CDI/10,000 PD; range: 13.9-75.5/10,000 PD). The testing frequency and CDI incidence rate were highly correlated (R2 = 0.91). Of the 146 isolates, RT018/018″ was dominant (29%), followed by types 014 (23%), 002 (12%), and 369 (11%). Among the 15 non-ICU wards, two had high CDI incidence rates (13.0 and 15.9 CDI/10,000 PD), with clusters of RT018/slpA-ST smz-02 and 018"/smz-01, respectively. Three non-RT027 or 078 binary toxin-positive isolates were found. All RT018/018" isolates were resistant to moxifloxacin, gatifloxacin, clindamycin, and erythromycin. This study identified a higher CDI incidence in Japanese hospitals than previously reported by actively identifying and testing patients with clinically significant diarrhea. This suggests numerous patients with CDI are being overlooked due to inadequate diagnostic testing in Japan.

Fertility preservation in adolescent and young adult cancer patients: From a part of a national survey on oncofertility in Japan.

PURPOSE: This study evaluated the current status of reproductive disorders and provision of information on oncofertility to female adolescent and young adult (AYA) cancer patients in Japan. METHODS: A national survey of AYA cancer survivors was conducted. Children were <15 years old, and AYAs were 15-39 years old. Results from the survivors of other than gynecological disease who underwent chemotherapy were analyzed. RESULTS: Among the survivors, 41.4% were concerned about their reproductive function and infertility, and 36.2% were aware of menstrual cycle abnormalities. Among them, 15.5% (n = 20) of all and 21.2% (n = 17) of the AYA-onset survivors suffered infertility due to chemo- or radiotherapy and gave up childbearing. These rates were significantly higher than those of healthy AYAs. Although 80.8% of AYA-onset survivors answered that they had received information on reproductive function and infertility, only 55.8% had received information on fertility preservation methods. Furthermore, only 22.4% of all and 42.3% of AYA-onset survivors had received pretreatment information on fertility preservation methods. CONCLUSIONS: Not a few AYA cancer survivors reported reproductive dysfunction. These findings indicate that information provided on therapy-related problems before cancer treatment in Japan was insufficient and highlight the need to improve patient decision-making and support systems for fertility preservation.

Problems of reproductive function in survivors of childhood- and adolescent and young adult-onset cancer revealed in a part of a national survey of Japan.

PURPOSE: This study aimed to evaluate the current status of reproductive disorders as long-term complications in adolescent and young adult (AYA) cancer patients by comparing survivors of childhood-onset with those of AYA-onset cancer in Japan. METHODS: We conducted a national survey of AYA cancer survivors and healthy AYAs and analyzed the results from survivors who underwent chemotherapy and reported fertility problems as their current concern. RESULTS: Among all of the childhood-onset survivors, 27 (35.5%; nine males [28.1%] and 18 females [40.9%]) listed reproduction fertility problems as their current concern. Among all AYA-onset survivors, 25 (69.5%; 1/4 males [25.0%] and 24/32 females [75.0%]) listed these problems as a current concern. In contrast, 96.3% (26/27) of all childhood-onset cancer survivors and 68.0% (17/25) of all AYA-onset cancer survivors who received chemotherapy listed these problems as a current concern. CONCLUSIONS: A considerable number of both childhood-onset and AYA-onset cancer survivors, and especially those who had undergone chemotherapy, reported reproductive dysfunction as a delayed complication. It is vitally important to establish a supportive care system both for the patients whose fertility was abolished after the completion of cancer treatment and prophylactically for patients before they begin treatment.

A Pilot Study of Prediction of Creatinine Clearance by Ellipsoid Volumetry of Kidney Using Noncontrast Computed Tomography.

INTRODUCTION: Aging is associated with a decline in kidney volume and function. The purpose of this study is to investigate a direct relationship between kidney volume and function in the elderly population and to challenge whether kidney function could be predictable by using the kidney volume. METHODS: We conducted a chart review of 366 patients who underwent abdominal computed tomography (CT) and renal function measurement prior to gastrointestinal surgery. The kidney volume was calculated by the ellipsoid method using a coronal section of noncontrast CT images. RESULTS: The patients were 72.2 ± 13.2 years of age, and 39.0% were female. Their average measured creatinine clearance (mCCr) was 72.0 ± 21.5 mL/min. The average kidney volume was 100.3 ± 27.6 cm3 in the right kidney and 109.3 ± 30.9 cm3 in the left. There was a significant positive correlation between the total kidney volume and mCCr. Multivariate regression analysis showed that age, diabetes mellitus, and total kidney volume were dependent variables with which to predict mCCr. The use of total kidney volume predicted mCCr of ≥50 mL/min with moderate accuracy (area under the curve = 0.782; 95% confidence interval = 0.692-0.871). CONCLUSIONS: These results indicate a direct relationship between kidney volume and function in the elderly and might provide a pilot method which estimates the renal function using kidney morphology obtained from pre-existing CT images.

Correction to: Current situation of cancer among adolescents and young adults in Japan.

In the original publication, Tables 4 and 5 have not been published in a readable format. The corrected clear version is given in this Correction.

Current situation of cancer among adolescents and young adults in Japan.

BACKGROUND: Cancer is rare among adolescents and young adults (AYA). Affected persons need generation-specific attention and care; however, no nationwide study has investigated the medical care structure for AYA cancer treatment in Japan. METHODS: We conducted a nationwide survey of AYA cancer for frequency of AYA patients, type of cancer, medical facilities, and certified cancer professionals. Data were collected from 14,713 patients at 218 Core Cancer Treatment Hospitals. RESULTS: The average proportion of AYA cancer patients to all cancer patients was 3.6%. The median number of patients aged 15 to 24 years per hospital was small (n = 5, range 1-51). The most frequent primary site of AYA cancer was the cervix uteri, but when cancer in situ was excluded, the hematopoietic malignancies were the most frequent cancer in males and females aged 15-24 years. In the age group 25-39 years, testicular and breast cancers were the most frequent cancers in males and females, respectively. Certified cancer professionals and facilities are necessary for appropriate care of AYA cancer patients, but the availability of such professionals varied greatly among hospitals. Hospitals with few AYA cancer patients were less likely to employ such physicians. CONCLUSIONS: The present findings suggest that medical care for AYA cancer in Japan requires further refinement and a multidisciplinary approach.