Trend change of the transmission route of COVID-19-related symptoms in Japan.

OBJECTIVES: The Japanese prime minister declared a state of emergency on April 7 2020 to combat the outbreak of coronavirus disease 2019 (COVID-19). This declaration was unique in the sense that it was essentially driven by the voluntary restraint of the residents. We examined the change of the infection route by investigating contact experiences with COVID-19-positive cases. STUDY DESIGN: This study is a population-level questionnaire-based study using a social networking service (SNS). METHODS: To assess the impact of the declaration, this study used population-level questionnaire data collected from an SNS with 121,375 respondents (between March 27 and May 5) to assess the change in transmission routes over the study period, which was measured by investigating the association between COVID-19-related symptoms and (self-reported) contact with COVID-19-infected individuals. RESULTS: The results of this study show that the declaration prevented infections in the workplace, but increased domestic infections as people stayed at home. However, after April 24, workplace infections started to increase again, driven by the increase in community-acquired infections. CONCLUSIONS: While careful interpretation is necessary because our data are self-reported from voluntary SNS users, these findings indicate the impact of the declaration on the change in transmission routes of COVID-19 over time in Japan.

A Longer History of Hemodialysis Can Lead to Sarcopenia in Renal Transplantation Patients.

BACKGROUND: Sarcopenia is a condition in which the amount of skeletal muscle decreases. Recent studies have suggested that sarcopenia is a risk factor for the incidence of postoperative complications, longer hospitalization, and a poorer prognosis. In this study, we examined the impact of sarcopenia in association with a history of hemodialysis in renal transplantation patients. METHODS: A total of 157 patients who underwent renal transplantation at Yokohama City University Medical Center (Yokohama, Japan) from 2005 to 2016 were analyzed in this study. We determined the presence of sarcopenia using the psoas muscle index (PMI). The PMI was calculated based on the left psoas muscle area of L3 (mm2) divided by the square of the body height (m2). RESULTS: The mean/median length of time that the patients received hemodialysis was 2059/850 days. The PMI in men was significantly higher than that in women (321.9 ± 10.0 vs 226.6 ± 17.3, P < .001). The group with a longer history of hemodialysis (≥851 days) showed a significantly lower PMI than the short-history group (≤850 days) (355.8 ± 15.1 vs 289.7 ± 11.3, P = .001). The PMI showed a negative correlation according to the dialysis period and a positive correlation according to the sex and triglyceride levels. CONCLUSIONS: A longer history of hemodialysis was shown to be associated with a lower PMI in renal transplantation patients. In addition, the higher PMI group showed higher serum triglyceride levels than the lower PMI group.

Long-term Survival in a Kidney Transplantation Patient With Progressive Multifocal Leukoencephalopathy: A Case Report.

Post-kidney transplantation progressive multifocal leukoencephalopathy (PML) is a rare disease on which there are very few published reports on record. PML is a demyelinating disease caused by a destructive infection of the oligodendrocytes by the JC polyomavirus. No effective therapeutic protocol has been established other than measures to revive the immune function by reducing or discontinuing the administration of immunosuppressive agents. Most cases are progressive and show a poor prognosis. We herein report a case in which renal function has been maintained for 2 years following the onset of PML, which was initially diagnosed 3 years after kidney transplantation.

Effective Treatment With Everolimus for Recurrent Granulomatous Interstitial Nephritis in a Renal Transplant Recipient: A Case Report.

BACKGROUND: Granulomatous interstitial nephritis (GIN) is a rare renal disease, and its etiology remains unknown. We report recurrent GIN in renal allograft successfully treated with everolimus (EVR). CASE REPORT: A 22-year-old man with GIN received a kidney from his mother. On follow-up 8 months later, his serum creatinine level was increased, from 1.3 mg/dL to 1.7 mg/dL, and he had microhematuria and proteinuria. A protocol graft biopsy at 1 year after transplantation showed epithelioid granuloma with multinucleated giant cells. He received steroid pulse therapy for recurrent GIN twice, but he developed allograft dysfunction, hematuria, and proteinuria. EVR was started in combination with maintenance immunosuppressants at 28 months after transplantation. Thereafter, the serum creatinine level decreased, from 2.1 mg/dL to 1.6 mg/dL, and microhematuria and proteinuria were stable despite reduction of steroid dose. CONCLUSIONS: Maintenance immunosuppressive therapy combined with EVR may be effective for the recurrence of idiopathic GIN in renal allograft.

Influence of cytochrome P450 3A5 polymorphisms on viral infection incidence in kidney transplant patients treated with tacrolimus.

OBJECTIVE: The aim of this retrospective study was to determine the risk of viral infection in tacrolimus-treated kidney transplant patients. METHODS: We analyzed kidney transplant recipients from 2002 to 2012, reporting all episodes of viral infection. All patients received induction with basiliximab followed by a standard regimen with tacrolimus, steroids, and antimetabolites. Genotypes of cytochrome P450 (CYP) 3A5 were determined with the use of the polymerase chain reaction method. RESULTS: Fifty-one patients (17 women, 34 men; mean age, 41.6 ± 65.7 years) underwent kidney transplantation with tacrolimus-based immunosuppressive therapy. Thirty patients were diagnosed with 34 viral infections, including herpes simplex, adenovirus, mumps, varicella, and cytomegalovirus (CMV). CMV was the most common viral infection. In multivariate analysis, the CYP3A5 1 allele (P = .049) and negative serology for CMV (P = .018) were factors independently associated with the incidence of viral infection. After excluding CMV infection in CMV-seropositive donor/CMV-seronegative (D+R-) recipients in the analysis, the presence of the CYP3A5 1 allele was found to be an independent risk factor for viral infection. Recipients with the CYP3A5 3/3 genotype (nonexpressors) showed significantly higher dose-adjusted tacrolimus trough concentrations than patients with the CYP3A5 1 allele (expressors; respectively, 104.6 ± 65.6 vs 52.6 ± 62.3 ng/mL per mg/kg/d). CONCLUSIONS: The CYP3A5 1 allele is associated with viral infection, possibly as a result of higher peak concentrations of tacrolimus. Further analyses, such as area under the concentration-time curve (AUC) for tacrolimus and polymorphisms of drug metabolism enzymes such as CYP3A4 are required to evaluate the influence of CYP3A5 on viral infection in kidney transplantation.

Efficacy of rebamipide enemas in active distal ulcerative colitis and proctitis: a prospective study report.

Rebamipide has a broad spectrum of pharmacological actions that include suppression of neutrophil functions and stimulation of mucosal epithelial cell regeneration by increasing the expression of epithelial growth factor (EGF) and the EGF receptor. Sixteen patients with active ulcerative colitis (UC; mild in 1 patient, moderate in 11, and severe in 4) were recruited. Enemas containing 150 mg rebamipide per dosing were administered during the daytime after passage of stool, twice a day for 4 weeks. UC disease activity index (UC-DAI), endoscopic activity index (EAI), and Floren's grading (FG) of mucosal biopsy specimens were measured at entry and at 4 weeks. Five of 16 patients did not complete the study, and therefore, final efficacy assessment was done on 11 patients who completed the 4 weeks of treatment. Improvements were observed in UC-DAI (P = 0.0049), EAI (P = 0.0043), and FG (P = 0.0084). There was no serious rebamipide-related side effect in any of the 16 patients. In conclusion, rebamipide topical therapy appears to be effective for the treatment of mildly to moderately active distal UC. Further controlled studies are warranted for this promising drug.

Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis.

BACKGROUND: The newer 5-ASA preparations were intended to avoid the adverse effects of SASP while maintaining its therapeutic benefits. The efficacy and safety of 5-ASA preparations have been evaluated in numerous clinical trials that have often lacked sufficient statistical power to arrive at definitive conclusions. Previously, it was found that newer 5-ASA drugs were more effective than placebo but no more effective than SASP in inducing remission in ulcerative colitis. This updated review includes more recent studies and evaluates the effectiveness, dose-responsiveness, and safety of 5-ASA preparations in terms of more precise outcome measures. OBJECTIVES: To assess the efficacy, dose-responsiveness and safety of the newer release formulations of 5-aminosalicylic acid (5-ASA) compared to placebo or sulfasalazine (SASP) in the maintenance of remission in ulcerative colitis. SEARCH STRATEGY: A computer-assisted literature search for relevant studies (1981-2002) was performed using MEDLINE, BIOS, the Cochrane Controlled Trials Register, the Cochrane IBD Group Specialized Trials Register, and the Science Citation Index, followed by a manual search of reference lists from previously retrieved articles, review articles, symposia proceedings, and abstracts from major gastrointestinal conferences. SELECTION CRITERIA: Studies were accepted for analysis if they were prospective, randomized, double-blinded, and placebo- or SASP-controlled clinical trials of parallel design with treatment duration of at least six months. DATA COLLECTION AND ANALYSIS: Based on an intention to treat principle, the primary outcome was the failure to maintain clinical or endoscopic remission. Secondary outcomes were the number of patients experiencing adverse events, the number of patients withdrawn due to adverse events, and exclusions or withdrawals after entry into the study (not due to relapse). All data were analyzed using the Peto odds ratio and corresponding 95% confidence intervals (CI). MAIN RESULTS: The Peto odds ratio for the failure to maintain clinical or endoscopic remission (withdrawals and relapses) for 5-ASA versus placebo was 0.47 (95% CI, 0.36 to 0.62) with an NNT of 6. These values were also calculated for the trials in which SASP and 5-ASA were compared, revealing an odds ratio of 1.29 (95% CI, 1.05 to 1.57), with a negative NNT value (-19), suggesting a higher degree of therapeutic effectiveness for SASP. SASP and 5-ASA had similar adverse event profiles, with odds ratios of 1.16(0.62 to 2.16), and 1.31(0.86 to 1.99), respectively. The NNH values were determined to be 171 and 78 respectively. REVIEWER'S CONCLUSIONS: The newer 5-ASA preparations were superior to placebo in maintenance therapy. However, the newer preparations had a statistically significant therapeutic inferiority relative to SASP. This review updates the existing review of oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis which was published in the Cochrane Library (Issue 3, 2002).

Efficacy of treatment with chimeric monoclonal antibody (Infliximab) to tumor necrosis factor-alpha for Crohn's disease in Japan: evaluation by rapid turnover proteins, and radiologic and endoscopic findings.

BACKGROUND: Several studies have reported that the chimeric monoclonal antibody to tumor necrosis factor (TNF)-alpha (Infliximab) is extremely valuable in the treatment of Crohn's disease. The aim of this study was to clarify the efficacy of this treatment in Japanese patients with Crohn's disease. METHODS: A 12-week multicenter, open trial of Infliximab was carried out and involved 25 patients with moderate to severe Crohn's disease who were resistant to conventional treatment. Patients received a single 2-h intravenous infusion of Infliximab at a dose of 1, 3, 5 or 10 mg/kg bodyweight. Clinical evaluation of this treatment response was defined as a reduction in the index of the inflammatory bowel disease (IOIBD) and of the Crohn's disease activity index scores (CDAI), and in serum levels of C-reactive protein (CRP) at 2, 4, 8 and 12 weeks, and as an increase in serum levels of rapid turnover proteins as well as improvement of radiologic and endoscopic findings at 4 weeks. RESULTS: The IOIBD score was reduced after 4 weeks in 66.7% of the group receiving 1 mg/kg Infliximab, 71.4% in the group receiving 3 mg/kg, 80.0% in the group receiving 5 mg/kg, and 85.7% in the group receiving 10 mg/kg. Improvement was better maintained over 12 weeks in the 5 and 10 mg/kg groups compared with the 1 and 3 mg/kg groups. Similar results were obtained for the CDAI scores. Serum levels of rapid turnover proteins significantly increased to within the normal ranges after infusion in all groups. Seven of the 11 (63.6%) patients evaluated showed improvement of radiologic and endoscopic findings. CONCLUSIONS: A single infusion of Infliximab was effective for the treatment of Japanese patients with Crohn's disease. Serum rapid turnover proteins reflected the clinical response to antibody for TNF-alpha well.

The syllable method: proportion of impaired syllables as an indicator of spasmodic dysphonia severity.

We have previously proposed the 'mora method' to evaluate the degree of impairment in spasmodic dysphonia (SD) in Japanese-speaking patients. With this method, impairment is judged as the proportion of impaired morae in a 25-mora sentence in a longer passage read aloud. As the mora is the phonologically isochronic unit in Japanese, the proportion of impaired morae in speech can be used to represent the temporal proportion of impaired Japanese speech. This proportional measure of impairment reflects the perceived severity of the impairment, and is a more reliable measure than a 4-point perceptual rating scale completed either by patients or by voice professionals. In this paper, we propose a 'syllable method' to characterize the severity of impairment in English-speaking SD patients. Instead of morae, the severity of SD was represented by the proportion of impaired syllables. It should be possible to characterize SD impairments more reliably and precisely with this method than using a 4-point rating scale completed by voice professionals. Ultimately, the syllable method should become a simple and effective method for evaluating the severity of SD. Furthermore, such methods can be applied to other languages, using the appropriate phonological unit (either mora or syllable).

Long-term analysis of suprapubic cystostomy drainage in patients with neurogenic bladder.

OBJECTIVE: We assessed the roles of suprapubic cystostomy in patients with neurogenic bladder and analyzed the complications and their courses. PATIENTS AND METHODS: We reviewed 118 patients with neurogenic bladder managed with suprapubic cystostomy. The original diseases were spinal cord injury in 90, degenerative disease of the central nervous system in 15, spina bifida in 6, cerebral palsy in 3, pontine bleeding in 1, Parkinson's disease in 1, brain tumor in 1, and dysgenesis of the external sphincter in 1. Fifty-six (62.2%) of spinal cord-injured patients demonstrated cervical damage. Renal function, urinary pH and white blood cell values were measured and evaluated after insertion. The stone-free rate after insertion was estimated by the Kaplan-Meier method. RESULTS: Indications for cystostomy were failure of clean intermittent catheterization in 62 (52.5%) and Credé's maneuver in 2, severe urethral damage in 30 (25.4%), replacement of urethral catheter in 3, worsening of the original disease in 15 (12.7%), deterioration of the general condition in 2, mental retardation in 2, and traumatic vesical rupture in 1. Frequent complications were formation of the bladder calculi in 30 (25%) and urinary leakage through the urethra in 11 (10%). No fatal complications occurred. The stone-free rates 5 and 10 years after insertion were 77 and 64%, respectively. The urinary pH of the stone-forming group was significantly higher than that of the stone-free group. The high urinary pH group (>7.24) had a higher risk of stone formation. CONCLUSIONS: Although continuous cystostomy drainage is not considered to be ideal management for bladder emptying, some patients with neurogenic bladder may benefit from this procedure.

Oral 5-aminosalicylic acid for inducing remission in ulcerative colitis.

OBJECTIVES: To assess the efficacy, dose-responsiveness and safety of the newer release formulations of 5-aminosalicylic acid (5-ASA) compared to placebo or sulfasalazine (SASP) for the induction of remission in active ulcerative colitis. SEARCH STRATEGY: A computer-assisted literature search for relevant studies (1981-1998) was performed using MEDLINE, BIOS, the Cochrane Controlled Trials Register and the Science Citation Index, followed by a manual search of reference lists from previously retrieved articles, review articles, symposia proceedings, and abstracts from major gastrointestinal conferences. SELECTION CRITERIA: Studies were accepted for analysis if they were randomized, double-blinded, and controlled clinical trials of parallel design, with treatment durations of a minimum of four weeks. DATA COLLECTION AND ANALYSIS: Based on an intention to treat principle, the outcomes of interest in the treatment of active disease were the failure to induce global/clinical remission, global/clinical improvement, endoscopic remission, or endoscopic improvement. MAIN RESULTS: 5-ASA was superior to placebo with regard to all measured outcome variables. For the failure to induce global/clinical improvement or remission, the pooled Peto odds ratio was 0.51 (95% CI, 0.35 to 0.76). A dose-response trend for 5-ASA was also observed. When 5-ASA was compared to SASP, the pooled Peto odds ratio was 0.87 (CI, 0.63 to 1.21) for the failure to induce global/clinical improvement or remission, and 0.66 (CI, 0.42 to 1.04) for the failure to induce endoscopic improvement. SASP was not as well tolerated as 5-ASA. REVIEWER'S CONCLUSIONS: The newer 5-ASA preparations were superior to placebo and tended towards therapeutic benefit over SASP. However, considering their relative costs, a clinical advantage to using the newer 5-ASA preparations in place of SASP appears unlikely.

Oral 5-aminosalicylic acid for maintaining remission in ulcerative colitis.

OBJECTIVES: To assess the efficacy, dose-responsiveness and safety of the newer release formulations of 5-aminosalicylic acid (5-ASA) compared to placebo or sulfasalazine (SASP) in the maintenance of remission in ulcerative colitis. SEARCH STRATEGY: A computer-assisted literature search for relevant studies (1981-1998) was performed using MEDLINE, BIOS, the Cochrane Controlled Trials Register, the Inflammatory Bowel Disease Trials Register, and Science Citation Index, followed by a manual search of reference lists from previously retrieved articles, review articles, symposia proceedings, and abstracts from major gastrointestinal conferences. SELECTION CRITERIA: Studies were accepted for analysis if they were prospective, randomized, double-blinded, and placebo- or SASP-controlled clinical trials of parallel design with treatment duration of at least six months. DATA COLLECTION AND ANALYSIS: Based on an intention to treat principle, the primary outcome was the failure to maintain clinical or endoscopic remission. Secondary outcomes were the number of patients experiencing adverse events, the number of patients withdrawn due to adverse events, and exclusions or withdrawals after entry into the study (not due to relapse). All data were analyzed using the Peto odds ratio and corresponding 95% confidence intervals (CI). MAIN RESULTS: The Peto odds ratio for the failure to maintain clinical or endoscopic remission (withdrawals and relapses) for 5-ASA versus placebo was 0. 47 (95% CI, 0.36 to 0.62) with an NNT of 6. These values were also calculated for the trials in which SASP and 5-ASA were compared, revealing an odds ratio of 1.29 (95% CI, 1.05 to 1.57), with a negative NNT value (-19), suggesting a higher degree of therapeutic effectiveness for SASP. SASP and 5-ASA had similar adverse event profiles, with odds ratios of 1.16(0.62 to 2.16), and 1.31(0.86 to 1.99), respectively. The NNH values were determined to be 171 and 78 respectively. REVIEWER'S CONCLUSIONS: The newer 5-ASA preparations were superior to placebo in maintenance therapy. However, the newer preparations had a statistically significant therapeutic inferiority relative to SASP.

Effect of intrarectal prostaglandin E2 analogue (enprostil) on trinitrobenzenesulphonic acid-induced colitis in rats.

Prostaglandins exert a protective effect on colonic mucosa in experimentally induced colitis. This study investigated the effect of enprostil, a prostaglandin E2 (PGE2) analogue, on trinitrobenzenesulphonic acid (TNBS)-induced colitis in rats. Each rat received a rectal enema containing TNBS (30 mg), followed 24 h later by intrarectal once-daily enprostil (200 microg). Enprostil-treated and control rats were killed on day 3 (enprostil group, n = 5; control, n = 6) or day 10 (enprostil group, n = 5; control, n = 5) after TNBS treatment. The area of damaged mucosa of the colon was measured relative to the total colonic area. We also determined the macroscopic score of mucosal damage, and measured PGE2, 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) and thromboxane B2 (TXB2) concentration in portal vein blood samples. Enprostil significantly reduced both the area of damaged mucosa (including the ulcer area) and the macroscopic score after 3 days' treatment compared with control. Similarly, enprostil significantly reduced plasma concentration of PGE2, 6-keto-PGF1alpha and TXB2 during the acute phase at day 3 of treatment compared with control, but not at day 10. These results suggest that PGE2 enema may have therapeutic potential for treating patients with proctitis or left-sided colitis.

Cyclin E overexpression in transitional cell carcinoma of the bladder.

We attempted to clarify the relationship between cyclin E to p27(Kip1), Ki-67 and clinicopathologic features in transitional cell bladder carcinoma. Immunohistochemical staining of archival tissue specimens of transitional cell bladder carcinoma obtained from 94 patients was performed by the labeled streptavidin-biotin-peroxidase method. Overexpression of cyclin E protein was observed in 38 of the 94 (40.4%) specimens, and was positively correlated with histological grade, Ki-67 LI and p27(Kip1) labeling index (LI). These data suggest that cyclin E may be associated with aggressive tumor growth, and may have a relationship with p27(Kip1) for the regulation of cell cycle progression in transitional cell bladder carcinoma.

Cyclin-dependent kinase inhibitor p27(Kip1) expression in transitional cell carcinoma of renal pelvis and ureter.

We examined the expression and significance of p27(Kip1) protein in 79 patients with transitional cell carcinoma of the renal pelvis and ureter. Immunohistochemical staining of archival tissue specimens was done using a labeled streptavidin-biotin-peroxidase method. There was no significant association between p27(Kip1) labeling index and histologic grade or pathologic stage. Patients with p27(Kip1) labeling indices of 27 or greater had more favorable prognoses in comparison to those with p27(kip1) labeling indices less than 27 (P<0.01). Multivariate analysis indicated that p27(Kip1) had an independent predictive prognostic value (P<0.05). The p27(Kip1) may be a novel prognostic marker for transitional cell carcinoma of the renal pelvis and ureter.