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.

iMusta4SLC: Database for the structural property and variations of solute carrier transporters.

Membrane transporter proteins play important roles in transport of nutrients into the cell, in transport of waste out of the cell, in maintenance of homeostasis, and in signal transduction. Solute carrier (SLC) transporter is the superfamily, which has the largest number of genes (>400 in humans) in membrane transporter and consists of 52 families. SLC transporters carry a wide variety of substrates such as amino acids, peptides, saccharides, ions, neurotransmitters, lipids, hormones and related materials. Despite the apparent importance for the substrate transport, the information of sequence variation and three-dimensional structures have not been integrated to the level of providing new knowledge on the relationship to, for instance, diseases. We, therefore, built a new database named iMusta4SLC, which is available at http://cib.cf.ocha.ac.jp/slc/, that connected the data of structural properties and of pathogenic mutations on human SLC transporters. iMusta4SLC helps to investigate the structural features of pathogenic mutations on SLC transporters. With this database, we found that the mutations at the conserved arginine were frequently involved in diseases, and were located at a border between the membrane and the cytoplasm. Especially in SLC families 2 and 22, the conserved residues formed a large cluster at the border. In SLC2A1, one third of the reported pathogenic missense mutations were found in this conserved cluster.

Employment status and termination among survivors of pediatric brain tumors: a cross-sectional survey.

BACKGROUND: Some childhood cancer survivors experience employment difficulties. This study aimed to describe pediatric brain-tumor survivors' employment status. METHODS: A cross-sectional, observational study was conducted, with questionnaires distributed to 101 pediatric brain-tumor survivors (aged 15 years or older) and their attending physicians from nine institutions in Japan. We compared category and time-series histories for participants' first-time employment using national census information. Factors related to delayed employment or early employment termination were examined using survival-time analyses. RESULTS: Excluding students and homemakers, 38 brain-tumor survivors (median age 27 years, with 15 years since diagnosis) were of working age. Of these, 12 (32%) were unemployed and 9 (24%) had never been employed. First-time employment occurred later for brain-tumor survivors than the general population, particularly in those with lower educational levels. The number of brain-tumor survivors whose first job was terminated within the first year was higher than that for the general population, particularly in male survivors and germ cell-tumor survivors. Brain-tumor survivors described their working patterns (irregular), job types (specialist or professional), reasons for early termination (unsuitable job), and thoughts about working (they wished to serve their communities but lacked confidence). CONCLUSION: Brain-tumor survivors are associated with high unemployment rates and multiple unemployment-related factors. Education and welfare systems should identify individual methods of social participation for this group.

Impact of age on postoperative complication rates among elderly patients with hip fracture: a retrospective matched study.

This study was performed to assess the impact of age of ≥ 90 years on predicting postoperative complications. We retrospectively identified all patients aged ≥ 65 years who underwent surgical repair of hip fractures over a 4.5-year period in our hospital. In total, 261 patients were identified (mean age, 86.2 ± 6.8 years). Ninety-one patients were aged ≥ 90 years (oldest-old group), and the remaining 170 were aged < 89 years (control old group). Postoperative complications developed in 54 of 261 patients (20.7%). The oldest-old group had a significantly higher proportion of patients with a Japanese long-term care insurance need level and trochanteric fracture than the control group. Spinal anesthesia was more frequently performed in the oldest-old group. After propensity adjustment for these characteristics, postoperative complication rates in the oldest-old group remained significantly higher than those in the matched control group (odds ratio (OR) 2.76, 95% confidence interval (95% CI) 1.24-6.49; P = 0.011). Major complications also developed more frequently in the oldest-old group than control group (OR 9.78, 95% CI 1.31-4.36; P = 0.018). Anesthesiologists and surgeons should pay attention to potential complications following hip fracture surgery for patients aged ≥ 90 years regardless of American Society of Anesthesiologists class or social dependency.

A case of descending mediastinitis caused by Streptococcus pyogenes harboring genotype emm25 and sequence type 660.

Descending mediastinitis caused by Streptococcus pyogenes (group A streptococcus, GAS) is rare among cases of invasive GAS infection. In this report, we describe a case of a cervical abscess and secondary descending mediastinitis in a previously healthy 39-year-old Japanese man. The patient presented with a 2-week history of a sore throat, and subsequently developed an abscess and descending mediastinitis. We treated the cervical abscess using ampicillin/sulbactam and drainage, and GAS was subsequently isolated in two blood cultures from the patient's admission. Microbiological analyses revealed that the isolate harbored genotype emm25 and sequence type (ST) 660. This strain was susceptible to erythromycin (minimum inhibitory concentration [MIC]: ≤0.12 µg/mL), resistant to minocycline (MIC: >4 µg/mL), and possessed the tet(M) determinant. Although we have reviewed the literature regarding the clinical and microbiological characteristics of descending mediastinitis cause by GAS, little is known regarding epidemiological and clinical characteristics of emm25/ST660 GAS. Furthermore, to best of our knowledge, this is the first reported case of descending mediastinitis caused by emm25/ST660 GAS. Therefore, physicians should be aware of case with a cervical abscess and secondary descending mediastinitis caused by GAS infection, even if the patient is immunocompetent.

Peripherally inserted central catheter-related bloodstream infection caused by Kocuria marina in an elderly man.

BACKGROUND: Kocuria species are Gram-positive, aerobic cocci, and members of the Micrcoccaceae family that are known to be opportunistic pathogens. Although there have been sporadic reports of infections caused by Kocuria species, little is known regarding their human pathogenicity and clinical characteristics. CASE REPORT: We herein report a case of a peripherally inserted central catheter (PICC)-related bloodstream infection caused by Kocuria marina in a 90-year-old Japanese with multiple cancer. The patient, who was admitted due to adhesive intestinal obstruction, suddenly developed sepsis on day 29 following admission. Three sets of blood cultures and a culture of the PICC tip revealed the growth of Gram-positive cocci arranged in clusters. The patient improved quickly after treatment with an antimicrobial agent and catheter removal. The organism was identified as Kocuria varians using the MicroScan Walkaway system and K. varians/Kocuria rosea with a 99.7% probability using an API Staph system. However, 16S rRNA gene sequencing analysis identified the pathogen as K. marina. CONCLUSION: Although K. marina is a rare pathogen, physicians should consider it in case of catheter-related infections in patients with serious underlying conditions. As commercial identification systems can misidentify species within the Kocuria genus, the use of genomic methods such as 16S rRNA sequencing and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry may be useful for the precise identification of Kocuria to the species level.

Role of Caveolin-1 for Blocking the Epithelial-Mesenchymal Transition in Proliferative Vitreoretinopathy.

Purpose: Proliferative vitreoretinopathy (PVR) is one of the most severe ocular diseases. Fibrotic changes in retinal cells are considered to be involved in the pathogenesis of PVR. Epithelial-mesenchymal transition (EMT) of RPE cells is one of the main concepts in the pathogenesis of fibrovascular membranes (FVMs) in PVR. In this study, we examined the expression of Caveolin-1 in human FVMs from patients with PVR. We also examined the role of Caveolin-1 in the pathogenesis of PVR. Methods: Western blotting, real-time PCR, and immunohistochemistry were performed with human FVMs and mouse eyes with PVR. Cell migration assays were performed to evaluate the involvement of Caveolin-1 in EMT using primary human and mouse RPE cells. Results: Caveolin-1 was expressed in human FVMs and upregulated in the mouse eyes with PVR. The alpha-smooth muscle actin (αSMA) expression and migration ability were increased in RPE cells with knockout or knockdown of Caveolin-1, whereas zonula occludens-1 (ZO-1) immunohistochemistry showed reduced morphology and expression of ZO-1. In addition, migration assays showed that Caveolin-1 reduction increased RPE cell migration abilities. Conclusions: These results indicated that Caveolin-1 in RPE cells prevents PVR by blocking EMT.

Characteristics of mucoid Streptococcus pyogenes isolated from two patients with pneumonia in a local community.

Streptococcus pyogenes (Group A Streptococcus, GAS) infections can develop into life-threatening disorders. However, the occurrence of some GAS pneumonia cases is relatively rare in a local community. We report here characteristics of mucoid GAS isolates obtained from the sputum of two patients with pneumonia in a local community. Although case-patients did not have contact with each other, case-patient 1's child and case-patient 2's grandchild attended the same kindergarten where a GAS pharyngitis epidemic had occurred. We conducted phenotypic and genotypic analyses with the GAS isolates from sputum of both patients, to examine (1) colony appearance between the isolates, (2) numerical profile based on API-20 Strep system, (3) similarity to the type strain using 16S rRNA sequencing, (4) emm type (subtype) and emm full-length sequence, (5) sequence type, (6) sic allele, (7) antimicrobial susceptibility result and the resistance determinant, (8) genome profile following a random amplified polymorphic DNA fragments, and (9) pattern of digested DNA fragments by pulse-field gel electrophoresis. These phenotypic and genotypic analyses revealed similar matching between the isolates from both cases. Our findings suggest that when clinicians examine adult patients having infection with the mucoid GAS, they should confirm whether anyone within the same household also developed the infection and need to investigate epidemic situations in local communities, including kindergartens and elementary schools.

[Meningococcal Septicemia Revealing Multiple Myeloma: A Case Report].

Meningococcal infection is among the most devastating diseases. It is rarely seen in Japan. However, several environmental and host factors have been associated with increased risks of Neisseria meningitidis infection. We present a case of invasive N. meningitidis infection that revealed the presence of multiple myeloma. A 55-year-old Japanese man was admitted with fever and altered consciousness. He was sent to the intensive care unit for septic shock and disseminated intravascular coagulation. In addition to standard septic shock and multiple organ failure treatment, polymyxin-B immobilized column direct hemoperfusion was performed. His blood culture was positive for N. meningitidis. The patient gradually improved and was discharged on day 35. We evaluated the risk factors for the development of meningococcal infection. A laboratory examination showed that the patient was negative for human immunodeficiency virus antibody and had a normal total complement function. However, his serum immunoglobulin G level was high, and serum and urine protein electrophoresis detected a monoclonal gammopathy. A bone marrow examination led to the diagnosis of multiple myeloma. Because N. meningitidis bacteria spreads between individuals in close contact through the exchange of oral secretions, droplet precautions and antimicrobial chemoprophylaxis (ciprofloxacin, 500 mg) were implemented to prevent the spread of the meningococcal infection. Sporadic meningococcal infection warrants an evaluation for immunodeficiency and the prevention of secondary infection.

Increased Ocular Levels of MicroRNA-148a in Cases of Retinal Detachment Promote Epithelial-Mesenchymal Transition.

PURPOSE: The purpose of this study was to determine microRNA expression in vitreous and subretinal fluid (SRF) samples from patients with retinal detachment (RD). The pathological importance of the identified microRNA transcript levels was analyzed in vitro. METHODS: Vitreous fluid was collected from 10 patients with macular hole (MH), vitreomacular traction syndrome (VMTS), or foveoschisis and from 11 patients with RD. Subretinal fluid was collected from 7 patients with RD. Of these, blood serum was collected in 4 patients. MicroRNA microarray profiling was performed to identify microRNA transcripts that were present in vitreous fluid, and more redundantly detected in SRF, of patients with RD, but not detected in control eyes. Western blotting and scratch assays were performed in ARPE-19 cells and primary human RPE cell lines transfected with microRNA to elucidate the effect of identified microRNA transcripts on epithelial-mesenchymal transition (EMT). RESULTS: MicroRNA microarray profiling revealed that hsa-miR-148a-3p was the most redundantly detected transcript in SRF and vitreous fluid from patients with RD, but not those with the other diseases. Expression levels of hsa-miR-148a-3p were higher in SRF samples than in blood serum samples in 3 out of 4 patients. Following hsa-miR-148a-3p mimic transfection, ARPE-19 and human RPE cells demonstrated increased expression of α-smooth muscle actin by Western blotting and increased migration ability during scratch assays. CONCLUSIONS: The results of the present study indicate that hsa-miR-148a-3p was specifically detected in RD and promotes EMT in RPE.

A higher body mass index attenuates the long-term HbA1c-lowering effects of liraglutide in type 2 diabetes patients treated using sulfonylurea-based therapy.

OBJECTIVE: To identify the attenuating factor of glycated hemoglobin (HbA1c)-lowering effects of liraglutide in type 2 diabetes (T2D) patients over the long term. METHODS: Forty-six T2D patients received liraglutide-glimepiride combination therapy. Clinical characteristics were compared between the following two subgroups: the relapse group (≥0.4 % increase in HbA1c in 48 weeks compared to 12 weeks) and non-relapse group (remaining patients). A glucagon-loading test was performed to evaluate baseline endogenous insulin secretion. RESULTS: In the relapse group, significantly reduced HbA1c, as observed at 12 weeks, tended to increase at 24 and 48 weeks. In the non-relapse group, reduced HbA1c was maintained for 48 weeks. Body weight was decreased at 12 weeks and then recovered at 48 weeks in both groups. Baseline BMI was significantly higher in the relapse group than in the non-relapse group. Age, HbA1c, duration of diabetes, fasting C-peptide, daily glimepiride dose and the duration of glimepiride treatment were comparable between both groups. Multiple logistic regression analysis revealed that baseline BMI was independently associated with the relapse group. CONCLUSION: A higher BMI is the leading factor for attenuating long-term glycemic control by liraglutide in T2D patients undergoing sulfonylurea-based therapy.