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Dai Aoki,1,2 Nobuyuki Kajiwara,3,4 Keiko Irishio,5 Yasuhiro Kato,6 Shinya Suezaki,1 Misaki Kageyama,1 Masahiro Misago,1 Daisuke Tamai,7 Shinichiro Nakao,1 Takato Ueoka,1 Mototoshi Ito,1 Shinichiro Murakami1,4 1Department of Emergency and General Medicine, Ikeda City Hospital, Ikeda, Osaka, Japan; 2Fukuchiyama City Hospital Ooe-Branch, Fukuchiyama, Kyoto, Japan; 3Department of Nephrology, Ikeda City Hospital, Ikeda, Osaka, Japan; 4Toyono Town National Health Insurance Clinic, Toyono, Osaka, Japan; 5Department of Clinical Research, Ikeda City Hospital, Ikeda, Osaka, Japan; 6Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan; 7Tamai Medical Clinic, Hannan, Osaka, JapanCorrespondence: Dai AokiDepartment of Emergency and General Medicine, Ikeda City Hospital, 3-1-18 Johnan, Ikeda, Osaka, 563-8510, JapanTel +81-72-751-2881Fax +81-72-754-6380Email 1000.0.d511@gmail.comObjective: A total of 105 patients (64 women) who were started on glucocorticoid (GC) treatment for polymyalgia rheumatica (PMR) and/or remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome at Ikeda City Hospital from July 2004 to December 2019 were reviewed (PMR: 81, overlap: 20, pure RS3PE syndrome: 4). Then, 32 cases that had stopped GC and 17 cases that had continued GC for 7.5 years or longer were evaluated (women:men, stopped GC 12:20, continued GC 13:4, respectively) (PMR:overlap:pure RS3PE syndrome, stopped GC 26:6:0, continued GC 14:2:1, respectively).Methods: The GC continuation rate in all patients was examined using the Kaplan–Meier method. The following were compared between the two groups: age at starting GC; sex; erythrocyte sedimentation rate, C-reactive protein, hemoglobin, ferritin, aspartate aminotransferase, and alanine aminotransferase before starting GC; days from the onset of symptoms to GC initiation; GC maximum dose; GC dose half a year after its start; presence of relapse; and existence of concomitant malignant disease.Results: The GC continuation rate 7.5 years after GC initiation was 52.5%, higher in women (69.2%), than in men (27.1%). The rates then remained unchanged for 15 years. Hemoglobin was high, and relapse was uncommon in the group that stopped GC. There were no differences in other items.Conclusion: It is difficult to stop GC therapy for PMR in women in Japan, especially in cases with severe anemia.Keywords: discontinuation of therapy, glucocorticoid, polymyalgia rheumatica, remitting seronegative symmetrical synovitis with pitting edema syndrome, sex difference

BackgroundSchool urinary screening has been performed in Japan.MethodsIkeda City and Toyono Town introduced, in 2012 and 2013, urinary protein/creatinine (Cr) ratio measurement into the urine-screening protocols designed for students aged between 4 and 15 years. For each student whose urinary protein/Cr ratio was ≥ 0.15 g/gCr (positive case), an appointment was made with a specialist at Ikeda City Hospital. The results of these screening urinalyses conducted through 2018 are summarized.Results14,606 junior high and elementary school students aged between 6 and 15 years were included. On average, they underwent 4.16 screening tests. 77 positive cases were detected, and seven students were diagnosed with high-risk chronic kidney disease (CKD). Of these, four underwent renal biopsy, and two, one, and one were diagnosed with IgA nephropathy, MPGN, and FSGS, respectively. In three students, detection of CKD would have been difficult without urinary screening. Incident rates of high-risk CKD and IgA nephropathy are estimated as 11.5 and 3.3 cases/100,000 students/year. 78.0% of positive cases without high-risk CKD showed no urinary abnormality after one year. 2301 kindergarten students aged between 4 and 6 years received an average of 1.74 screening urinalyses; none was positive or high-risk CKD. The estimated cost of detecting one high-risk CKD student whose detection would have been difficult without this screening was 3,156,711 Japanese yen.ConclusionSchool urinary screening using the urinary protein/Cr ratio can efficiently refer to a specialist. It detects a few children with high-risk CKD early with spending high cost.

Key Clinical Message Membranous nephropathy associated with malignant neoplasm may remit completely with treatment of the underlying disease. In such cases, recurrence is very rare. However, after a recurrence, attention should be paid to the possible recurrence of the underlying disease.

Key Clinical Message Sjögren's syndrome concurrent with protein‐losing gastroenteropathy can develop into secondary systemic capillary leak syndrome. Thus, it is important to diagnose the condition as soon as possible and simultaneously administer treatment for Sjögren's syndrome, protein‐losing gastroenteropathy, and systemic capillary leak syndrome.

Nobuyuki Kajiwara,1 Kazuyuki Hayashi,1 Masahiro Misago,2 Shinichiro Murakami,2 Takato Ueoka2 1Department of Nephrology, Ikeda City Hospital, 2Department of General Medicine, Ikeda City Hospital, Johnan, Osaka, Japan Purpose: We sought to profile first-time patients without a referral who sought medical care at the Department of Internal Medicine at a medium-sized acute care hospital in Japan. We anticipated that the analysis would highlight the demand for medical care needs from acute care hospitals and help confirm one of the problems associated with primary care in Japan. Patients and methods: The study population comprised 765 patients who sought outpatient consultation without a referral at “the Department of General Internal Medicine” at the Ikeda City Hospital on Fridays over 4 years. Data on the following variables were collected: age, sex, examination date, reason for encounter (RFE), diagnosis, as well as history of consultation with or without antibiotic treatment at another medical institution for the same RFE. We used the International Classicication of Primary Care, Revised Second edition (ICPC-2-R) codes for RFEs and diagnoses. Results: The main RFE fields were digestive (ICPC-2-R Chapter D), general and unspecified (A), and respiratory (R). The main diagnosis fields were digestive (D), respiratory (R), general and unspecified (A), and musculoskeletal (L). In total, 27.6% of patients had sought consultation at another medical institution for the same RFE. Of these, 64.7% of patients for whom the RFE was cough (ICPC-2-R code, R05), and 72.0% for whom the RFE was fever (A03) were prescribed antibiotics. In total, 62.4% of patients underwent emergency investigations and waited for the results; 4.3% were hospitalized on the same day; and 60.5% were medicated at the initial examination. In 11.5%, the main underlying problem appeared to be psychosomatic. Conclusion: We used the ICPC-2-R to analyze the state of first-visit patients without a referral visiting the Department of Internal Medicine at a medium-sized acute care hospital in Japan. Common RFEs were abdominal pain, cough, and fever. A tendency toward overprescription of antibiotics was observed among primary care physicians. Keywords: medium-sized hospital, general internal medicine, general practice, reason for encounter, International Classification of Primary Care, antibiotic overuse

The insertion of a catheter into the mediastinum can occur in any patient as a complication. We must check for blood regurgitation not only in the blood removal line but also in the blood return line.

The cover image is based on the Case Report Case report: Gastric cancer‐associated membranous nephropathy that recurred after complete remission and formation of peritoneal dissemination by Nobuyuki Kajiwara et al., DOI: 10.1002/ccr3.2002.

Aim Renal damage has been reported as an important complication during combination treatment of peginterferon (PEG IFN), ribavirin (RBV) and telaprevir (TVR) for chronic hepatitis C. However, very little is known about this complication. We investigated the role TVR plays in renal damage during this triple therapy. Methods Twenty-five chronic hepatitis C patients with genotype 1 and high viral load received TVR in combination with PEG IFN and RBV for 12 weeks followed by treatment with PEG IFN and RBV. Renal function of these patients was prospectively evaluated for 16 weeks. Results Creatinine clearance decreased significantly during PEG IFN/RBV/TVR treatment. Consequently, serum creatinine and cystatin C significantly rose during PEG IFN/RBV/TVR treatment. Serum creatinine returned to pretreatment levels after the termination of TVR. The increase of serum creatinine and cystatin C from baseline significantly correlated with serum TVR level at day 7, which was determined by starting dose of TVR per bodyweight . When the patients were classified according to the starting dose of TVR per bodyweight, renal impairment was observed only in the high-dose (TVR ≥33 mg/kg per day) group, not in the low-dose (TVR

In order to explore the possible contribution of insulin-like growth factor I to the development of diabetic nephropathy, the effect of glucose on the mitogenic and metabolic actions of insulin-like growth factor I in cultured rat glomerular mesangial cells was examined. The stimulation of [3H]-thymidine incorporation by insulin-like growth factor I in the cells exposed to high concentrations (55 mmol/l) of glucose (4.6 +/- 1.3 fold stimulation) was significantly suppressed as compared with that in the cells cultured in 11 mmol/l glucose (17.5 +/- 0.8 fold). In contrast, [3H]-amino-isobutylic acid uptake into the mesangial cells was significantly enhanced by glucose (2.03 +/- 0.03 nmol.mg protein-1. 15 min-1 at 55 mmol/l glucose vs 0.59 +/- 0.01 at 11 mmol/l glucose), while 2-deoxyglucose uptake remained unchanged. [125I]-insulin-like growth factor I binding was slightly but significantly increased in the cells exposed to high concentrations of glucose. Thus, glucose may modulate the mitogenic and metabolic actions of insulin-like growth factor I differently in cultured mesangial cells probably at the post-insulin-like growth factor I receptor level. These results may indicate that the differential modulation of the actions of insulin-like growth factor I by glucose could result in the increase in amino acid uptake and decrease in the cell proliferation in the mesangial cells, possibly leading to enhanced mesangial matrix synthesis with a relatively small increase in mesangial cell volume as seen in diabetic nephropathy.

Dual mechanism of angiotensin II inhibits ANP-induced mesangial cGMP accumulation. To evaluate an interaction between vasoconstrictive (Ang II) 1 and vasodilating (Ang) peptides, we examined the effect of Ang II on ANP-induced accumulation of cGMP in cultured glomerular mesangial cells. ANP rapidly increased intracellular cGMP levels, with a peak stimulation at one minute in the absence of IBMX and at ten minutes in the presence of IBMX. The ANP-induced cGMP accumulation was significantly inhibited when the cells were treated with Ang II simultaneously with ANP for one minute in the absence of IBMX. This inhibitory effect of Ang II was completely abolished by IBMX and significantly reduced in calcium-free media or by W7, but not affected by H7. Similar inhibitory effect was observed when cells were treated with A23187 but not with TPA for one minute. In the presence of IBMX, Ang II inhibited ANP-induced cGMP accumulation when cells were treated with Ang II for 15 minutes prior to the stimulation by ANP. This inhibition by Ang II was blocked by H7. ANP-induced increase in particulate guanylate cyclase activity was significantly reduced in the cells treated with Ang II or TPA. This reduction of enzyme activity was also prevented by H7. These results indicate that Ang II inhibits ANP-induced cGMP accumulation in cultured glomerular mesangial cells through at least two mechanisms; one is the activation of calcium-dependent, calmodulin-stimulated cyclic nucleotide phosphodiesterase in the initial phase, and the other is the inhibition of guanylate cyclase resulting from protein kinase C activation in the maintenance phase.

Type IV collagen production by cultured glomerular mesangial cells and the effect of glucose on it were evaluated in order to explore the possible contribution of mesangial cells to the accumulation of type IV collagen in mesangial matrix typically seen in diabetes. Type IV collagen was measured quantitatively by enzyme-linked immuno-sorbent assay. The majority of type IV collagen was secreted into culture media and secreted-type IV collagen increased with cell growth in early log phase and decreased in late log phase and after confluency. By exposing the cells to high concentrations of glucose (27.8 mmol/l), both secreted- and cell-associated-type IV collagens increased significantly compared with the cells cultured under normal glucose concentrations (5.6 mmol/l) or under equivalent concentrations of mannitol, resulting in a significant increase in total type IV collagen accumulation from 32.1 +/- 6.4 (under 5.6 mmol/l glucose) to 51.0 +/- 4.6 micrograms/dish (mean +/- SD, n = 4) on day 4, from 113.6 +/- 6.6 to 156.8 +/- 7.1 on day 6, from 248.5 +/- 15.2 to 310.0 +/- 12.6 on day 8 and from 372.4 +/- 14.8 to 507.9 +/- 17.2 on day 12. These results indicate the importance of glucose-induced alteration of mesangial cell function in the development of diabetic mesangial expansion.

Background Annual urinary screening is conducted at municipal kindergartens, elementary schools, and junior high schools in Ikeda City, Osaka, Japan (Ikeda City School System), and the results are reviewed by a general physician, but standards for when to recommend specialist referral have not been clear. Methods In all children attending the Ikeda City School System in 2012, dipstick urinalysis of a first-morning urine specimen was recommended once or twice, and if a second urinalysis showed proteinuria (≥1+), the urinary protein/creatinine ratio was measured. If this showed ≥0.2 g/g of creatinine (g/gCr), it was recommended that the child be evaluated by a specialist at Ikeda City Hospital. Results Urinary screening was performed in about 20% (388) of kindergarten, about 90% (5363) of elementary school, and about 86% (2523) of junior high school children living in Ikeda City. Urine samples were obtained from 387, 5349, and 2476 children, respectively. The urinary protein/creatinine ratio was ≥0.2 g/gCr in 13 children, including 1 elementary and 12 junior high children. In these 13 children, chronic nephritic syndrome (CNS) was suspected in 6 junior high school children, and of these, this was a new finding in 5, and renal biopsy was indicated in 3. In Ikeda City, the prevalence of CNS in elementary school children was