Plasma Exchange Therapy to Reduce Mortality in Japanese Patients With Diffuse Alveolar Hemorrhage and Microscopic Polyangiitis

Diffuse alveolar hemorrhage (DAH) is well known as a serious complication of microscopic polyangiitis (MPA). We examined the effectiveness of plasma exchange (PLEX) therapy to reduce mortality in Japanese DAH patients with MPA. This retrospective, double‐center, observational cohort study included 20 DAH patients with MPA who were admitted to Juntendo University Hospital or Juntendo Koto Geriatric Medical Center between April 1998 and March 2018. The primary outcome was non–disease‐specific mortality. The 1‐year survival rate of patients with PLEX therapy (N = 4) was higher than that of patients with conventional therapy (N = 16, 75% and 13%, respectively, P = 0.037). Higher values of the 1996 Five‐Factor Score (FFS) and 2009 FFS were associated with increased mortality, with hazard ratios of 2.29 (P = 0.040) and 2.41 (P = 0.043), respectively, by Cox univariate analysis. We investigated PLEX therapy for reducing mortality in DAH patients with MPA, and the 1996 FFS and 2009 FFS were both independent prognostic factors.     

Association of sleep‐disordered breathing with decreased cognitive function among patients with dementia

Sleep is known to be essential for proper cognitive functioning. Sleep disturbance, especially respiratory disturbance during sleep, is a risk factor for the development of dementia. However, it is not known whether hypopnoea during sleep is related to severity of cognitive function in patients already diagnosed with dementia. Considering the high prevalence of sleep problems in aged people, it is important to determine if hypopnoea during sleep contributes to dementia. In addition, it would be desirable to develop a feasible method for objectively evaluating sleep in patients with dementia. For this purpose, a simple sleep recorder that employs single or dual bioparameter recording, which is defined as a type‐4 portable monitor, is suitable. In this study, a type‐4 sleep recorder was used to evaluate respiratory function during sleep in 111 patients with dementia, and data suggesting a possible relationship with cognitive function levels were examined. Multivariate logistic regression was used to investigate the association of severity of dementia with sleep‐disordered breathing, age, diabetes, dyslipidaemia and hypertension. It was found that the respiratory disturbance index was associated with severity of cognitive dysfunction in our subjects. Furthermore, patients younger than 80 years were more susceptible to lower cognitive function associated with sleep‐disordered breathing than patients 80 years old or over, because an increase in the respiratory disturbance index was associated with deteriorated cognitive function only in the former age group. These results suggest that proper treatment of sleep apnea is important for the preservation of cognitive function, especially in patients with early‐stage dementia.     

Short‐ and long‐term effect of sitagliptin after near normalization of glycemic control with insulin in poorly controlled Japanese type 2 diabetic patients

Aims/Introduction

The aim of the present study was to examine the short‐ and long‐term effect of sitagliptin on glucose tolerance after near normalization of glycemic control with insulin in poorly controlled type 2 diabetic patients.

Materials and Methods

We consecutively enrolled a total of 30 type 2 diabetic patients whose glycated hemoglobin levels (National Glycohemoglobin Standardization Program) were ≥7.4%, stopped all oral antidiabetic drugs and started insulin therapy. When fasting plasma glucose levels became <140 mg/dL, we carried out the first oral glucose tolerance test (OGTT). After 1‐week sitagliptin treatment (50 mg/day), the second OGTT was carried out. Furthermore, we evaluated the long‐term efficacy of sitagliptin on glucose tolerance after near normalization of glycemic control with insulin.

Results

After 1‐week sitagliptin treatment, the area under the curve of insulin was markedly increased, and the area under the curve of glucagon and glucose was markedly decreased. Duration of diabetes and insulin secretory capacity were correlated with the effect of sitagliptin. Furthermore, interestingly, near normalization of glycemic control with insulin therapy for 1–2 weeks brought out the long‐term effectiveness of sitagliptin on glucose tolerance for 24 weeks, which was not observed with other antidiabetic drugs.

Conclusions

These findings suggest that near normalization of glycemic control with insulin improves the clinical response to sitagliptin in poorly controlled type 2 diabetic patients.     

FACTORS ASSOCIATED TO ADHERENCE TO DIFFERENT TREATMENT SCHEMES WITH MEGLUMINE ANTIMONIATE IN A CLINICAL TRIAL FOR CUTANEOUS LEISHMANIASIS

The favorable outcome of the treatment of a disease is influenced by the adherence to therapy. Our objective was to assess factors associated with adherence to treatment of patients included in a clinical trial of equivalence between the standard and alternative treatment schemes with meglumine antimoniate (MA) in the treatment of cutaneous leishmaniasis (CL), in the state of Rio de Janeiro. Between 2008 and 2011, 57 patients with CL were interviewed using a questionnaire to collect socioeconomic data. The following methods were used for adherence monitoring: counting of vial surplus, monitoring card, Morisky test and modified Morisky test (without the question regarding the schedule); we observed 82.1% (vial return), 86.0% (monitoring card), 66.7% (Morisky test) and 86.0% (modified Morisky test) adherence. There was a strong correlation between the method of vial counting and the monitoring card and modified Morisky test. A significant association was observed between greater adherence to treatment and low dose of MA, as well as with a lower number of people sleeping in the same room. We recommend the use of the modified Morisky test to assess adherence to treatment of CL with MA, because it is a simple method and with a good performance, when compared to other methods.     

Diagnostic criteria for pancreaticobiliary maljunction 2013

Pancreaticobiliary maljunction is a congenital malformation in which the pancreatic and bile ducts join anatomically outside the duodenal wall. The diagnostic criteria for pancreaticobiliary maljunction were proposed in 1987. The committee of The Japanese Study Group on Pancreaticobiliary Maljunction (JSGPM) for diagnostic criteria for pancreaticobiliary maljunction began to revise the diagnostic criteria from 2011 taking recently advanced diagnostic imaging techniques into consideration, and the final revised version was approved in the 36^th Annual Meeting of JSPBM. For diagnosis of pancreaticobiliary maljunction, an abnormally long common channel and/or an abnormal union between the pancreatic and bile ducts must be evident on direct cholangiography, such as endoscopic retrograde cholangiopancreatography, percutaneous transpehatic cholangiography, or intraoperative cholangiography; magnetic resonance cholangiopancreatography; or three‐dimensional drip infusion cholangiography computed tomography. However, in cases with a relatively short common channel, it is necessary to confirm that the effect of the papillary sphincter does not extend to the junction by direct cholangiography. Pancreaticobiliary maljunction can be diagnosed also by endoscopic ultrasonography or multi‐planar reconstruction images provided by multi‐detector row computed tomography. Elevated amylase levels in bile and extrahepatic bile duct dilatation strongly suggest the existence of pancreaticobiliary maljunction.     

The rational design of a synthetic polymer nanoparticle that neutralizes a toxic peptide in vivo

Synthetic polymer nanoparticles (NPs) that bind venomous molecules and neutralize their function in vivo are of significant interest as "plastic antidotes." Recently, procedures to synthesize polymer NPs with affinity for target peptides have been reported. However, the performance of synthetic materials in vivo is a far greater challenge. Particle size, surface charge, and hydrophobicity affect not only the binding affinity and capacity to the target toxin but also the toxicity of NPs and the creation of a "corona" of proteins around NPs that can alter and or suppress the intended performance. Here, we report the design rationale of a plastic antidote for in vivo applications. Optimizing the choice and ratio of functional monomers incorporated in the NP maximized the binding affinity and capacity toward a target peptide. Biocompatibility tests of the NPs in vitro and in vivo revealed the importance of tuning surface charge and hydrophobicity to minimize NP toxicity and prevent aggregation induced by nonspecific interactions with plasma proteins. The toxin neutralization capacity of NPs in vivo showed a strong correlation with binding affinity and capacity in vitro. Furthermore, in vivo imaging experiments established the NPs accelerate clearance of the toxic peptide and eventually accumulate in macrophages in the liver. These results provide a platform to design plastic antidotes and reveal the potential and possible limitations of using synthetic polymer nanoparticles as plastic antidotes.