Diagnostic criteria for atypical hemolytic uremic syndrome proposed by the joint committee of the Japanese society of nephrology and the Japan pediatric society

Atypical hemolytic uremic syndrome (aHUS) is rare and comprises the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Recently, abnormalities in the mechanisms underlying complement regulation have been focused upon as causes of aHUS. The prognosis for patients who present with aHUS is very poor, with the first aHUS attack being associated with a mortality rate of ~25 %, and with ~50 % of cases resulting in end-stage renal disease requiring dialysis. If treatment is delayed, there is a high risk of this syndrome progressing to renal failure. Therefore, we have developed diagnostic criteria for aHUS to enable its early diagnosis and to facilitate the timely initiation of appropriate treatment. We hope these diagnostic criteria will be disseminated to as many clinicians as possible and that they will be used widely.     

Significance of combined cyclosporine−prednisolone therapy and cyclosporine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome: a randomized controlled multicenter trial

Background

Combined treatment with cyclosporine microemulsion preconcentrate (CyA MEPC) and steroids has been widely used for idiopathic membranous nephropathy (IMN) associated with steroid-resistant nephrotic syndrome (SRNS). Recent studies have shown that once-a-day and preprandial administration of CyA MEPC is more advantageous than the conventional twice-a-day administration in achieving the target blood CyA concentration at 2 h post dose (C2). We designed a randomized trial to compare these administrations.

Methods

IMN patients with SRNS (age 16–75 years) were divided prospectively and randomly into 2 groups. In group 1 (n = 23), 2–3 mg/kg body weight (BW) CyA MEPC was given orally once a day before breakfast. In group 2 (n = 25), 1.5 mg/kg BW CyA MEPC was given twice a day before meals. CyA + prednisolone was continued for 48 weeks.

Results

Group 1 showed a significantly higher cumulative complete remission (CR) rate (p = 0.0282), but not when incomplete remission 1 (ICR1; urine protein 0.3–1.0 g/day) was added (p = 0.314). Because a C2 of 600 ng/mL was determined as the best cut-off point, groups 1 and 2 were further divided into subgroups A (C2 ≥600 ng/mL) and B (C2 <600 ng/mL). Groups 1A and 2A revealed significantly higher cumulative remission (CR + ICR1) (p = 0.0069) and CR-alone (p = 0.0028) rates. On the other hand, 3 patients with high CyA levels (C2 >900 ng/mL) in Group 1A were withdrawn from the study because of complications.

Conclusion

CyA + prednisolone treatment is effective for IMN with associated SRNS at a C2 of ≥600 ng/mL. To achieve remission, preprandial once-a-day administration of CyA at 2–3 mg/kg BW may be the most appropriate option. However, we should adjust the dosage of CyA by therapeutic drug monitoring to avoid complications.     

Effects of etizolam and ethyl loflazepate on the P300 event-related potential in healthy subjects

Background

Benzodiazepines carry the risk of inducing cognitive impairments, which may go unnoticed while profoundly disturbing social activity. Furthermore, these impairments are partly associated with the elimination half-life (EH) of the substance from the body. The object of the present study was to examine the effects of etizolam and ethyl loflazepate, with EHs of 6 h and 122 h, respectively, on information processing in healthy subjects.

Methods

Healthy people were administered etizolam and ethyl loflazepate acutely and subchronically (14 days). The auditory P300 event-related potential and the neuropsychological batteries described below were employed to assess the effects of drugs on cognition. The P300 event-related potential was recorded before and after drug treatments. The digit symbol test, trail making test, digit span test and verbal paired associates test were administered to examine mental slowing and memory functioning.

Results

Acute administration of drugs caused prolongation in P300 latency and reduction in P300 amplitude. Etizolam caused a statistically significant prolongation in P300 latency compared to ethyl loflazepate. Furthermore, subchronic administration of etizolam, but not ethyl loflazepate, still caused a weak prolongation in P300 latency. In contrast, neuropsychological tests showed no difference.

Conclusions

The results indicate that acute administration of ethyl loflazepate induces less effect on P300 latency than etizolam.     

Reduction in the magnitude of serum potassium elevation in combination therapy with esaxerenone (CS‐3150) and sodium–glucose cotransporter 2 inhibitor in patients with diabetic kidney disease: Subanalysis of two phase III studies

Aims/IntroductionWe evaluated the effect of co‐administration of esaxerenone and a sodium–glucose cotransporter 2 (SGLT2) inhibitor on the magnitude of serum potassium elevation in Japanese patients with diabetic kidney disease.Materials and MethodsWe carried out a prespecified subanalysis of data from two phase III studies: a multicenter, randomized, double‐blind, placebo‐controlled trial in patients with type 2 diabetes and microalbuminuria (J308); and a multicenter, single‐arm, open‐label trial in patients with type 2 diabetes and macroalbuminuria (J309). Changes in serum potassium levels during the studies and other measures were evaluated according to SGLT2 inhibitor use.ResultsIn both studies, time‐course changes in serum potassium levels, and incidence rates of serum potassium elevation were lower in patients with co‐administration of SGLT2 inhibitor in both the placebo and esaxerenone groups than those without the inhibitor. In contrast, time‐course changes and mean percentage changes from baseline in urinary albumin‐to‐creatinine ratio, the proportion of patients with albuminuria remission and time‐course changes in blood pressure did not change with or without SGLT2 inhibitor, whereas the albumin‐to‐creatinine ratio and blood pressure were reduced with esaxerenone. The blood glucose‐lowering effect of SGLT2 inhibitor was not affected by esaxerenone.ConclusionsIn Japanese patients with type 2 diabetes and albuminuria treated with esaxerenone, concomitant use of SGLT2 inhibitor reduced the magnitude of serum potassium elevation without any change of its antihypertensive and albuminuria‐suppressing effects. Co‐administration of esaxerenone and SGLT2 inhibitor might be a beneficial treatment option for patients with diabetic kidney disease.     

Possible effect of blonanserin on gambling disorder: A clinical study protocol and a case report

BACKGROUNDGambling disorder is characterized by excessive and recurrent gambling and can have serious negative social consequences. Although several psychotherapeutic and pharmacological approaches have been used to treat gambling disorder, new treatment strategies are needed. Growing evidence suggests that dopamine D3 receptor plays a specific role in the brain reward system.AIMTo investigate if blonanserin, a dopamine D3 receptor antagonist, would be effective in reducing gambling impulses in patients with gambling disorder.METHODSWe developed a study protocol to measure the efficacy and safety of blonanserin as a potential drug for gambling disorder, in which up to 12 mg/d of blonanserin was prescribed for 8 wk.RESULTSA 37-year-old female patient with gambling disorder, intellectual disability, and other physical diseases participated in the pilot study. The case showed improvement of gambling symptoms without any psychotherapy. However, blonanserin was discontinued owing to excessive saliva production.CONCLUSIONThis case suggests that blonanserin is potentially an effective treatment for patients with gambling disorder who resist standard therapies, but it also carries a risk of adverse effects. Further studies are needed to confirm the findings.     

Telecommunication system for children undergoing stem cell transplantation

Background: Isolation in a germ‐free unit is a stressful experience for pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). To reduce the psychological distress of such children, a Web‐based telecommunications system was developed. Methods: The authors developed a telecommunication system that linked a laminar air flow (LAF) room that had a high efficiency particulate air filter with the hospital school/patients' homes via the Internet. Fifteen children isolated in the LAF room for allogeneic HSCT were enrolled in this study. The present study evaluated whether the system was feasible for the patients during the acute phase of HSCT. Results: In 10 patients, the proportion of days when they telecommunicated with teachers and/or other patients in the hospital school was 64.6 ± 32.3%. The telecommunication with the hospital school facilitated the continuation of school study under teachers' guidance, reducing the problem of lost schooling. In 13 patients, the proportion of days when they telecommunicated with their homes was 68.0 ± 34.8%. Ten of them frequently telecommunicated with their family members (especially siblings), and three patients called out to their pets at home. The incidence of telecommunication on the days when the patients had HSCT‐related symptoms including vomiting did not differ from that of telecommunication on the days when no symptoms were evident. Conclusions: A telecommunication system linked to a hospital school and/or the patients' homes is feasible for children undergoing HSCT, and may improve their health‐related quality of life. A larger, prospective study is required to evaluate whether the telecommunication system can reduce HSCT‐associated psychological and psychiatric symptoms.     

The adenosine A2A receptor is associated with methamphetamine dependence/psychosis in the Japanese population

Background

Suicide and major depressive disorders (MDD) are strongly associated, and genetic factors are responsible for at least part of the variability in suicide risk. We investigated whether variation at the tryptophan hydroxylase-2 (TPH2) gene rs7305115 SNP may predispose to suicide attempts in MDD.

Methods

We genotyped TPH2 gene rs7305115 SNP in 215 MDD patients with suicide and matched MDD patients without suicide. Differences in behavioral and personality traits according to genotypic variation were investigated by logistic regression analysis.

Results

There were no significant differences between MDD patients with suicide and controls in genotypic (AG and GG) frequencies for rs7305115 SNP, but the distribution of AA genotype differed significantly (14.4% vs. 29.3%, p < 0.001). The G-allele frequency was significantly higher in cases than control group (58.1% vs.45.6%, p < 0.001), but the A-allele carrier indicated a decreased trend in MDD with suicide behaviors than control group (41.9% vs.54.4%, p < 0.001). The multivariate logistic regression analysis indicated that TPH2 rs7305115 AA (OR 0.33, 95% CI 0.22-0.99), family history of suicide (OR 2.98, 95% CI 1.17-5.04), negative life events half year ago (OR 6.64, 95% CI 2.48-11.04) and hopelessness (OR 7.68, 95% CI 5.79-13.74) were significantly associated with the suicide behaviors in MDD patients.

Conclusions

The study suggested that hopelessness, negative life events and family history of suicide were risk factors of attempted suicide in MDD while the TPH2 rs7305115A remained a significant protective predictor of suicide attempts.     

Improving the effect of NaOCl pretreatment on bonding to caries-affected dentin using self-etch adhesives

Objective

To evaluate the effect of sodium hypochlorite pretreatment on adhesion to normal and caries-affected dentin using self-etch adhesives.

Methods

Forty extracted human molars with coronal carious lesions were used in this experiment. The occlusal dentin surfaces including the caries-affected dentin in each group were treated as follows: group 1, rinsed with water; group 2, treated with 6% NaOCl for 15 s; group 3, treated with 6% NaOCl for 30 s; group 4, application with Accel for 30 s after NaOCl-30 s pretreatment. After rinsing with water and air-drying, the treated dentin surfaces were applied with self-etch systems (Bond Force and Clearfil Protect Bond) according to the manufacturers’ instructions, and built-up with resin composite. After 37 °C water storage for 24 h, the bonded normal or caries-affected dentin areas were isolated to create an hourglass configuration with a cross-sectional area of approximately 1 mm². The specimens were subjected to tensile stress at a cross-head speed of 1.0 mm/min.

Results

NaOCl-15 s pretreatment significantly improved the μTBS of both self-etch adhesives to caries-affected dentin, while the 30 s pretreatment did not affect them. For normal dentin, NaOCl-30 s pretreatment significantly reduced the μTBS of both self-etch adhesives although the 15 s pretreatment did not alter them. Furthermore, the application of Accel with a reducing effect increased the μTBS to normal and caries-affected dentin treated with NaOCl for 30 s.

Conclusions

The effects of NaOCl pretreatment on bonding of both self-etch adhesives were dependent upon type of dentin (normal and caries-affected dentin) and the treatment time.