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AIMS/INTRODUCTION: The study aim was to investigate sulfonylurea prescription patterns in elderly patients (age ≥65 years) with type 2 diabetes mellitus in Japan. Sulfonylurea use among older adults has been insufficiently examined, despite the associated risks of hypoglycemia. MATERIALS AND METHODS: This retrospective cross-sectional survey entailed analysis of Japanese pharmacy data, extracted from the Musubi database, for patients (age 20-100 years) prescribed sulfonylureas between November 2022 and October 2023. Dose distribution, adherence to the Diabetes Treatment Guidelines for the Elderly 2023 and coprescription of other diabetes medications were investigated. RESULTS: Of the total 91,229 patients, 80.1% were prescribed glimepiride, 16.3% gliclazide and 3.6% glibenclamide. In patients aged ≥65 years, exceeding the recommended dose (>1 mg/day for glimepiride, >40 mg/day for gliclazide) was numerically higher for glimepiride (25.0%) than for gliclazide (7.8%). The most common prescribing patterns were quadruple therapy with a sulfonylurea, a dipeptidyl peptidase-4 inhibitor, an sodium-glucose transporter 2 inhibitor and a biguanide in patients aged 65 to <75 years, and dual therapy with a sulfonylurea and a dipeptidyl peptidase-4 inhibitor in patients aged ≥75 years. Unfortunately, glinide was coprescribed for 338 (0.5%) of elderly patients. Insulin was coprescribed for 3,682 (5.6%) of elderly patients. CONCLUSIONS: Analysis of real-world sulfonylurea prescription data found guideline non-adherence, namely, excessive prescription of glimepiride, use of glibenclamide in elderly patients, and common coprescription with dipeptidyl peptidase-4 inhibitors. These findings might provide an opportunity to reconsider the treatment of patients with type 2 diabetes mellitus who are over-prescribed sulfonylureas to reduce residual risks, such as hypoglycemia.

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The coexistence of anti-glomerular basement membrane (anti-GBM) disease with thrombotic microangiopathy (TMA) is rarely encountered, and the clinical characteristics of this phenomenon are not well known.A 76-year-old Japanese woman with a history of idiopathic pulmonary disease was diagnosed with anti-GBM disease due to rapidly progressive glomerulonephritis and a positive anti-GBM antibody test result. We treated the patient with hemodialysis, glucocorticoids, and plasmapheresis. During treatment, the patient suddenly became comatose. TMA was then diagnosed because of thrombocytopenia and microangiopathic hemolytic anemia. The activity of a disintegrin-like and metalloproteinase with thrombospondin type 1 motif 13 (ADAMTS-13) was retained at 48%. Although we continued the treatment, the patient died of respiratory failure. An autopsy revealed the cause of respiratory failure to be an acute exacerbation of interstitial pneumonia. The clinical findings of the renal specimen indicated anti-GBM disease; however, there were no lesions suggestive of TMA. A genetic test did not reveal an apparent genetic mutation of the atypical hemolytic uremic syndrome.We conducted a literature review of past case reports of anti-GBM disease with TMA. The following clinical characteristics were obtained. First, 75% of the cases were reported in Asia. Second, TMA tended to appear during the treatment course for anti-GBM disease and usually resolved within 12 weeks. Third, ADAMTS-13 activity was retained above 10% in 90% of the cases. Fourth, central nervous system manifestations occurred in more than half of the patients. Fifth, the renal outcome was very poor. Further studies are required to understand the pathophysiology of this phenomenon.

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Purpose: Most previous studies that described associations between adult attention-deficit/hyperactivity disorder (ADHD) and sociodemographic characteristics were focused on individuals diagnosed with ADHD, and few studies investigated ADHD traits in the general population. Additionally, some workers, who experienced no problems while at university and successfully graduated from university, developed ADHD traits after finding employment. This study described associations between ADHD traits and sociodemographic characteristics among Japanese workers who were university graduates. Patients and Methods: Participants were randomly selected workers (n=1240) from across Japan who completed a self-administered online survey. ADHD traits were measured using an adult ADHD Self-report Scale, with scoring rules applied to reflect the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Information was collected on sociodemographic characteristics including sex, age, socioeconomic status, working time, and health-related behaviors. We performed partial correlation analysis to estimate trend associations and used analysis of covariance to compare adjusted averages. This model was adjusted for all variables. Results: Males had higher levels of ADHD traits than females (p = 0.001), and younger age was associated with higher levels of ADHD traits (p < 0.001). Workers with low incomes had higher levels of ADHD traits than workers with high incomes (p = 0.009). More frequent consumption of midnight meals was associated with higher levels of ADHD traits (p < 0.001), although there were no differences for breakfast, lunch, and dinner. Those who did not get enough rest from sleep had higher levels of ADHD traits (p = 0.007). Conclusion: Results for high levels of ADHD traits among workers were consistent with previous studies for adults diagnosed with ADHD, even though all participants had successfully graduated from university. Assessment of these ADHD traits may support prevention of health deterioration related to these ADHD traits.

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Granulocyte colony-stimulating factor (G-CSF) is commonly used to stimulate bone marrow production. G-CSF is usually safe but sometimes causes serious adverse effects and, in rare cases, exacerbates glomerulonephritis. We report a case of immunoglobulin A (IgA) nephropathy that was aggravated by G-CSF. A 56-year-old Japanese man with no relevant medical history was admitted to our hospital as a donor of peripheral blood stem cells (PBSCs) for transplantation. To mobilize PBSCs, he received subcutaneous G-CSF (lenograstim), 500 µg for 4 days. Three days after the first dose of lenograstim, gross hematuria appeared, and after administration on the fourth day, renal dysfunction and nephrotic-range proteinuria were observed. Renal biopsy and light microscopic study revealed mild mesangial proliferation with expansion in association with the presence of cellular segmental crescents. Immunofluorescence study revealed diffuse, granular staining in the mesangium for IgA, complement component 3 (C3), and lambda light chains. We diagnosed highly active IgA nephropathy and initiated treatment with prednisolone and azathioprine. Three months later, renal function returned to normal. Screening for hidden chronic glomerulonephritis should be performed when G-CSF is administered, as in PBSC donors. Immunosuppressant therapy, such as prednisolone or azathioprine, is considered for exacerbations of highly active glomerulonephritis.

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BACKGROUND: Previous studies have shown that GFR estimated from serum creatinine (eGFRcr) is higher in smokers although the implications remain unclear. We aimed to clarify the associations of smoking with eGFRcys (GFR estimated from serum cystatin C) and eGFRcr, cys (the surmised most precise GFR estimate based on serum creatinine and cystatin C) in a working population. METHODS: Cross-sectional observation in 1,587 male workers aged 25-64 years. For eGFRcr, JEQcr proposed by the Japanese Society of Nephrology (JSN) and jEPIcr by the Chronic Kidney Disease Epidemiological Collaboration (CKD-EPI) modified for Japanese, and for eGFRcys, JEQcys proposed by JSN and EPIcys by CKD-EPI were calculated together with eGFRcr,cys of JEQaver (the average of JEQcr and JEQcys) and jEPIcr,cys by CKD-EPI modified for Japanese. RESULTS: Mean JEQcys was 95.1 mL/min/1.73 m(2) in contrast to 80.9 in JEQcr, with this difference considerable. Serum cystatin C was higher in smokers and obese subjects while serum creatinine was lower in smokers and slender subjects. JEQcys and EPIcys were lower in smokers while JEQcr and jEPIcr were higher in smokers adjusting for body mass index (BMI). eGFRcr,cys (JEQaver and jEPIcr,cys) did not differ between the never smokers and current smokers. eGFRcr,cys predicted by the equations composed of eGFRcr, BMI, and smoking habits showed a good accordance with calculated eGFRcr,cys. CONCLUSIONS: Either eGFRcr, eGFRcys or both were not reliable indicators of renal function in workers who smoked. The possibly more precise estimate of eGFRcr,cys could be predicted by eGFRcr, BMI and smoking in such a generally healthy population.

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BACKGROUND: Smoking is a risk factor for chronic kidney disease (CKD). However, it is speculated that only a small subset of sensitive smokers develop CKD. OBJECTIVES: We aimed to reveal the characteristics of such smokers sensitive to the renal effects of smoking with respect to cardiovascular (CV) risk factors associated with smoking and/or CKD. PATIENTS AND METHODS: Renal functions and CVD risk factors were assessed in middle-aged male workers. The patients were comprised of 336 nonsmokers, 332 smokers currently smoking up to one pack per day, and 38 who smoked more than one pack per day. CKD was determined by estimated glomerular filtration rate (eGFR) from serum creatinine and urinary albumin to creatinine ratio (ACR). The independent and interactive effects of smoking and CKD on the CVD risk factors adjusted for age, body mass index, alcohol consumption, and physical activity were statistically analyzed. RESULTS: In comparison to nonsmokers, smokers had significantly higher waist circumference, white blood cells (WBC), serum triglycerides, γ-glutamyltransferase (GGT), and C-reactive protein (CRP) and lower serum high-density lipoprotein cholesterol and uric acid. On the other hand, blood pressure (BP) and WBC tended to be higher in those showing CKD than others. Serum GGT and fasting plasma glucose were significantly higher, and insulin resistance index of homeostatic model assessment (HOMA-IR) tended to be higher in those with CKD. Serum CRP was especially high in those with moderate to severe CKD. A significant interactive effect of smoking and CKD on BP and serum GGT levels was detected, i.e. BP and GGT were not different in the subjects among nonsmokers with and without CKD, but were conspicuously high among smokers with CKD. No significant interactive effect was found on either HOMA-IR or serum CRP. CONCLUSIONS: Smokers with a higher BP and/or serum GGT may be at a higher risk of developing CKD. The associations of BP and serum GGT with CKD in smokers are not entirely mediated by increased insulin resistance or chronic inflammation caused by smoking.

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BACKGROUND: Elevated serum gamma-glutamyltransferase (GGT) is predictive of various cardiovascular (CV) risk factors including chronic kidney disease (CKD). Elevated serum GGT has been recognized in smokers who are likely to develop CKD, but no study has focused on serum GGT and CKD in smokers. OBJECTIVES: The aim of this study was to clarify the associations between cigarette consumption, elevation of serum GGT and the development of proteinuria and CKD. PATIENTS AND METHODS: A retrospective 6-year observational study was conducted on 2,603 male workers aged between 40 and 64 years. Incidences of proteinuria detected by dipstick and CKD defined by proteinuria and/or reduced estimated glomerular filtration rate (eGFR) measured in health check-ups were determined 6 years later for those who had been free of them at baseline. RESULTS: Higher means of serum GGT in smokers than in nonsmokers at baseline, and a higher incidence of elevated serum GGT in smokers than in nonsmokers during the 6-year period were recognized only for alcohol consumers. Incidences of proteinuria and moderate or severe CKD which has a high risk of future renal failure or CV disease were higher in the subjects with greater cigarette consumption or a higher serum GGT level. Multiple logistic regression analyses adjusting for major CV risk factors showed a significant interactive effect between smoking and elevated serum GGT on the development of proteinuria and an additive effect of smoking and serum GGT on the development of high-risk CKD. CONCLUSIONS: Elevation of serum GGT in smokers, to a large extent, depends on the associated alcohol consumption. Elevated GGT in smokers plays at least a partial role in the development of CKD, mainly proteinuria, and the underlying mechanisms remain to be elucidated.

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Medical errors in pathological diagnosis give a huge amount of physical and psychological damage to patients as well as medical staffs. We discussed here how to avoid medical errors in surgical pathology laboratory through our experience. Handling of surgical specimens and diagnosing process requires intensive labor and involves many steps. Each hospital reports many kinds of accidents or incidents, however, many laboratories share common problems and each process has its specific risk for the certain error. We analyzed the problems in each process and concentrated on avoiding misaccessioning, mislabeling, and misreporting. We have made several changes in our system, such as barcode labels, digital images of all specimens, putting specimens in embedding cassettes directly on the endoscopic biopsied specimens, and using a multitissue control block as controls in immunohistochemistry. Some problems are still left behind, but we have reduced the errors by decreasing the number of artificial operation as much as possible. A pathological system recognizing the status of read or unread the pathological reports by clinician are now underconstruction. We also discussed about quality assurance of diagnosis, cooperation with clinicians and other comedical staffs, and organization and method. In order to operate riskless work, it is important for all the medical staffs to have common awareness of the problems, keeping careful observations, and sharing all the information in common. Incorporation of an organizational management tool such as ISO 15189 and utilizing PDCA cycle is also helpful for safety management and quality improvement of the laboratory.

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