Nighttime hypoglycemia in Japanese children with type 1 diabetes mellitus treated with multiple daily injection insulin therapy.

Prevention of hypoglycemia is an important strategy for glycemic management in patients with type 1 diabetes mellitus (T1D). Hypoglycemia is difficult to recognize at night while sleeping, particularly when using multiple daily injection (MDI) insulin therapy rather than sensor-augmented insulin-pump therapy. Therefore, it is possible that patients with T1D are at higher risk of nocturnal hypoglycemia when insulin is administered using an MDI regimen. We investigated nocturnal hypoglycemia in 50 pediatric patients with T1D on MDI insulin therapy using data from an intermittently scanned continuous glucose monitoring (isCGM) system. Hypoglycemia was observed on 446 of the 1,270 nights studied. Most of the hypoglycemic episodes were severe (blood glucose <54 mg/dL). On nights when hypoglycemia occurred, the blood glucose concentrations measured using finger-stick blood glucose monitoring (FSGM) before sleep and the next morning were lower than nights when hypoglycemia did not occur. However, few values were below the normal blood glucose range, suggesting that FSGM alone may be insufficient to detect nocturnal hypoglycemia. Approximately 7% of time was spent below the normal glucose range during the 10 hours from 21:00 to 7:00 the next morning. This result suggests that the patients on MDI insulin therapy could end up spending more time in hypoglycemia than is recommended by the American Diabetes Association (time below range <4.0% of time per day). Monitoring glucose levels overnight using an isCGM sensor may improve glycemic management via automatic detection of blood glucose peaks and troughs.

Epidemiology conduction of paediatric rheumatic diseases based on the registry database of the Pediatric Rheumatology Association of Japan.

OBJECTIVES: Although epidemiological surveys of paediatric rheumatic diseases in Japan have been conducted, they were single surveys with no continuity. This is the first report of the Pediatric Rheumatology Association of Japan registry database, which was established to continuously collect data for paediatric rheumatic diseases. METHODS: Pediatric Rheumatology International Collaborate Unit Registry version 2 (PRICUREv2) is a registry database established by the Pediatric Rheumatology Association of Japan. The registry data were analysed for the age of onset, time to diagnosis, sex differences, seasonality, and other factors. RESULTS: Our data showed the same trend regarding rates of paediatric rheumatic diseases reported in Japan and other countries. The age of onset was lower in juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis and higher in systemic lupus erythematosus and Sjögren's syndrome. The time to diagnosis was relatively short in JIA and systemic lupus erythematosus but longer in juvenile dermatomyositis and Sjögren's syndrome. Rheumatoid factor-positive polyarticular JIA showed a seasonality cluster with regard to onset. CONCLUSION: PRICUREv2 aided the retrieval and evaluation of current epidemiological information on patients with paediatric rheumatic diseases. It is expected that the data collection will be continued and will be useful for expanding research in Japan.

Potentially harmful excipients in neonatal medications: a multicenter nationwide observational study in Japan.

BACKGROUND: A multicenter investigation of neonate exposure to potentially harmful excipients (PHEs) in neonatal intensive care units (NICUs) in Japan has not been conducted. METHODS: A multicenter nationwide observational study was conducted. Neonate patient demographic data and information on all medicines prescribed and administered during hospitalization on 1 day between November 2019 and March 2021 were extracted from the medical records. Nine PHEs, paraben, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol, benzalkonium chloride, and aspartame, were selected. PHEs were identified from the package insert and the Interview Form. The quantitative daily exposure was calculated if quantitative data were available for each product containing the PHE. RESULTS: Prescription data was collected from 22 NICUs in Japan. In total, 343 neonates received 2360 prescriptions for 426 products containing 228 active pharmaceutical ingredients. PHEs were found in 52 (12.2%) products in 646 (27.4%) prescriptions for 282 (82.2%) neonates. Benzyl alcohol, sodium benzoates, and parabens were the most common PHEs in parenteral, enteral, and topical formulations, respectively. Quantitative analysis showed that 10 (10%), 38 (42.2%), 37 (94.9%), and 9 (39.1%) neonates received doses exceeding the acceptable daily intake of benzyl alcohol, polysorbate 80, propylene glycol, and sorbitol, respectively. However, due to the lack of quantitative information for all enteral and topical products, accurate daily PHE exposure could not be quantified. CONCLUSIONS: Neonates admitted to NICUs in Japan were exposed to PHEs, and several of the most commonly prescribed medicines in daily clinical practice in NICUs contained PHEs. Neonate PHE exposure could be reduced by replacing these medicines with available PHE-free alternatives.

[A Case of Effective Endovascular Treatment for Recurrent Bleeding from Advanced Breast Cancer].

A-58-year-old woman was diagnosed with breast cancer 8 years ago at another hospital, but refused surgical treatment. From 2 years ago, her skin invasion of cancer lesions began bleeding. The patient required frequent blood transfusions due to anemia associated with repeated bleeding. She was referred to our department for local treatment and palliative care. Diagnostic imaging revealed multiple lung, bone and liver metastasis. The patient refused to receive systemic chemotherapy, and she was recommended radiation therapy for repeated massive bleeding, but her consent was not obtained. She agreed to receive arterial embolization from the tumor-bearing vessels plus intravenous anti-cancer drug therapy. The hemostatic effect was observed for 4 to 5 weeks per treatment, and tumor reduction was also observed. She received a total of 6 treatments during 8 months until her death. These treatments were effective in maintaining quality of life at the end of life.

Zinc monotherapy for young children with presymptomatic Wilson disease: A multicenter study in Japan.

BACKGROUND AND AIM: Few studies of zinc monotherapy for presymptomatic Wilson disease have focused on young children. We therefore evaluated long-term efficacy and safety of zinc monotherapy for such children and established benchmarks for maintenance therapy. METHODS: We retrospectively and prospectively examined children under 10 years old with presymptomatic Wilson disease who received zinc monotherapy from time of diagnosis at 12 participating pediatric centers in Japan. RESULTS: Twenty-four patients met entry criteria. Aspartate aminotransferase and alanine aminotransferase decreased significantly beginning 1 month after initiation of treatment and usually remained under 50 U/L from 1 to 8 years of treatment. Twenty four-hour urinary copper decreased significantly at 6 months and usually remained under 75 µg/day and between 1 and 3 µg/kg/day for the remainder of the study. All patients continued to take zinc, and none became symptomatic. In patients under 6 years old who received 50 mg/day of zinc as an initial dose, aspartate aminotransferase and alanine aminotransferase significantly decreased at 1 month after initiation of treatment, as did γ-glutamyltransferase and 24-h urinary copper at 6 months. CONCLUSIONS: To our knowledge, this is the first multicenter study of zinc monotherapy for young children with presymptomatic Wilson disease. Such monotherapy proved highly effective and safe. Maintaining normal transaminase values (or values under 50 U/L when normalization is difficult) and 24-h urinary copper excretion between 1 and 3 µg/kg/day and under 75 µg/day is a reasonable goal. An initial dose of 50 mg/day is appropriate for patients under 6 years old.

A novel option for preoperative endoscopic marking with India ink in totally laparoscopic distal gastrectomy for gastric cancer: A useful technique considering the morphological characteristics of the stomach.

In totally laparoscopic distal gastrectomy (TLDG) for gastric cancer, accurately determining the proximal resection line may be difficult. This is because identifying the lesion intracorporeally is impossible, due to the lack of tactile sense, and, in addition, unlike the intestine, the most proximal site of the lesion is often different from the main site due to the distorted shape of the stomach. The aim of this study was to introduce a novel method of preoperative endoscopic marking with India ink, taking into consideration the morphological characteristics of the stomach. Between July, 2013 and April, 2016, 20 patients who underwent TLDG were enrolled in this study. Within the 3 days preceding the operation, after identifying the most proximal site of the lesion on the overlooking image of an endoscope, India ink was injected into the spot on the oral side of this site. The stomach was transected along the proximal border of the marked area. In all cases, the marked sites were localized and clearly identified during the operation, and the proximal resection margins were found to be negative on postoperative pathological examination. The mean length of the proximal margin was 46.0±14.0 mm. In conclusion, this preoperative endoscopic marking method may be useful in TLDG for gastric cancer.

Age-Adjusted Glycated Albumin at Diagnosis is more Correlated with the Product of Age and Plasma Glucose than Plasma Glucose Alone in Patients with Neonatal Diabetes Mellitus.

BACKGROUND: We previously showed that glycated albumin (GA) is a useful glycemic control indicator in patients with neonatal diabetes mellitus (NDM), and that age-adjusted GA (Aa-GA) can reflect more accurately glycemic control status. Here, we investigated whether the age at diagnosis influences Aa-GA at diagnosis of NDM. METHODS: Eight patients with NDM whose GA was measured at diagnosis (age at diagnosis: 39 ± 18 days; GA: 31.3 ± 7.6%; Aa-GA: 47.1 ± 10.3%; plasma glucose: 525 ± 194 mg/dl) were included. Aa-GA was calculated as follows: Aa-GA = GA × 14.0/[1.77 × log-age (days) + 6.65]. Correlations of GA or Aa-GA at diagnosis with its logarithmically transformed age in days (log-age), plasma glucose, and their product were investigated. RESULTS: GA at diagnosis was not significantly correlated with log-age or plasma glucose. On the other hand, Aa-GA at diagnosis was significantly positively correlated with plasma glucose (R = 0.75, P = 0.031) and was more strongly positively correlated with the product of plasma glucose and log-age (R = 0.82, P = 0.012) although it was not correlated with log-age. CONCLUSION: Aa-GA at diagnosis is influenced by both age in days and plasma glucose. This finding is likely to show the aspect that age in days is almost equal to diabetes duration because glycemic control indicators including GA reflect the weighted mean of plasma glucose.

A new option for intracorporeal circular-stapled esophagojejunostomy in laparoscopic total gastrectomy: Roux-en-Y reconstruction with its efferent loop located at the left side of the patient to prevent twisting of the esophagojejunostomy.

BACKGROUND/AIMS: Laparoscopic total gastrectomy (LTG) has not gained widespread acceptance because of the difficult reconstruction technique, especially for esophagojejunostomy. Although various modified procedures using a circular stapler for esophagojejunostomy have been reported, an optimal technique has not yet been established. In addition, in intracorporeal techniques, twisting of the esophagojejunostomy, which might be the cause of stenosis, is often encountered because application of the shaft is restricted. To prevent twisting of the esophagoejunostomy, we underwent LTG with Roux-en-Y reconstruction with its efferent loop located at the left side of the patient. METHODOLOGY: From November 2013 to November 2014, a series of 9 patients underwent LTG with Roux-en-Y reconstruction using the transorally inserted anvil (OrVil™, Covidien, Mansfield, MA, USA), whose efferent loop was located at the left side of the patient. RESULTS: No twisting of the esophagojejunostomy was encountered in all cases. In addition, no stenosis or leakage of the esophagojejunostomy occurred. CONCLUSIONS: This reconstruction system may be a feasible surgical procedure in LTG.

Vitamin K deficiency evaluated by serum levels of undercarboxylated osteocalcin in patients with anorexia nervosa with bone loss.

BACKGROUND & AIMS: Osteoporosis is a chief complication in patients with anorexia nervosa. Serum levels of undercarboxylated osteocalcin reflect serum and bone vitamin K deficiency. We investigated vitamin K status in patients with anorexia nervosa to help establish prevention and treatment recommendations for osteoporosis. METHODS: Fifty-four female amenorrheic patients with anorexia nervosa (29 restricting-type and 25 binge eating/purging type) (age, 28.0 (26.7-31.1) (mean (95% CI)) years; body mass index, 14.8 (14.1-15.5) kg/m(2), duration of illness; 107.3 (88.5-126.0) months) and 15 age-matched healthy females were included in this study. We measured serum levels of undercarboxylated osteocalcin, biochemical and nutritional markers, and bone metabolic markers. Dietary vitamin K intake was evaluated by a questionnaire. RESULTS: Lumbar bone mineral density and T-scores in patients with anorexia nervosa were 0.756 (0.721-0.790) g/cm(2) and -2.4 (-2.1 to -2.7), respectively, indicating bone loss. Serum levels of undercarboxylated osteocalcin in patients with anorexia nervosa were significantly higher than those of controls. The 17% of restricting type and 40% of binge eating/purging type anorexia nervosa patients, serum levels of undercarboxylated osteocalcin were higher than 4.5 ng/ml and were diagnosed with vitamin K deficiency. Serum levels of undercarboxylated osteocalcin correlated significantly and negatively with vitamin K intake in patients with anorexia nervosa. CONCLUSIONS: Patients with anorexia nervosa had vitamin K deficiency. Since a supplement of vitamin K might be effective for maintaining bone quality, we provide recommendations regarding vitamin K intake for prevention and treatment of osteoporosis in patients with AN.

Home parenteral nutrition therapy in seven patients with anorexia nervosa: the role and indications.

Home parenteral nutrition (HPN) is a well-established intervention to sustain life in malnourished patients at home. Because it is difficult for patients with anorexia nervosa (AN) to gain weight or stop purging, such patients require repeated hospitalizations. Although HPN has not been commonly used for AN patients in Japan, we utilized this approach to treat seven AN patients. We herein present the clinical course and outcome of these seven patients, the application criteria for HPN in our institution, and the potential problems associated with HPN. Despite its complications, HPN may be a useful measure to help patients with persistent AN avoid multiple hospitalizations.

Cosmetic evaluation following volume replacement using lateral tissue flap in breast-conserving surgery.

BACKGROUND: We examined the effectiveness of volume replacement using a lateral tissue flap (LTF) in breast-conserving surgery for a good cosmetic outcome. METHODS: We analyzed the results of 130 patients with breast cancer who underwent breast-conserving surgery with replacement using an LTF from 2006 to 2010 with cosmetic evaluations performed according to the criteria of the Japanese Breast Cancer Society. We examined scores with regard to the following possible contributing factors: partial resection (Bp) or quadrantectomy (Bq), diameter of the specimen, body mass index (BMI), axillary lymphadenectomy, postoperative irradiation, and position of the tumor. RESULTS: The scores for cases with Bp and non-postoperative irradiation were higher than those for Bq and postoperative irradiation cases, though they were not significant factors in multivariate analysis. A negative correlation was seen between score and diameter of the specimen, whereas there was no significant correlation with BMI. There was no significant difference between scores of cases with or without an axillary lymphadenectomy. However, the score for the extended upper-outer area including the upper and outer borders was significantly higher than scores for other portions. In multiple regression analysis, cases with a tumor diameter less than 4 cm in the extended upper-outer area or less than 2 cm in other areas showed good adaptation. CONCLUSION: Tumor location and diameter are important factors for cosmetic evaluation of volume replacement using an LTF.

Extraperitoneal Fluid Collection due to Chronic Pancreatitis.

A 39-year-old man was referred to our hospital for the investigation of abdominal fluid collection. He was pointed out to have alcoholic chronic pancreatitis. Laboratory data showed inflammation and slightly elevated serum direct bilirubin and amylase. An abdominal computed tomography demonstrated huge fluid collection, multiple pancreatic pseudocysts and pancreatic calcification. The fluid showed a high level of amylase at 4,490 IU/l. Under the diagnosis of pancreatic ascites, endoscopic pancreatic stent insertion was attempted but was unsuccessful, so surgical treatment (Frey procedure and cystojejunostomy) was performed. During the operation, a huge amount of fluid containing bile acid (amylase at 1,474 IU/l and bilirubin at 13.5 mg/dl) was found to exist in the extraperitoneal space (over the peritoneum), but no ascites was found. His postoperative course was uneventful and he shows no recurrence of the fluid. Pancreatic ascites is thought to result from the disruption of the main pancreatic duct, the rupture of a pancreatic pseudocyst, or possibly leakage from an unknown site. In our extremely rare case, the pancreatic pseudocyst penetrated into the hepatoduodenal ligament with communication to the common bile duct, and the fluid flowed into the round ligament of the liver and next into the extraperitoneal space.

[Relationship between care staff generativity and perceived job competence in elderly nursing homes].

AIM: According to Erikson's theory of ego development, generativity represents one task of adulthood. Generativity is defined as a concern for establishing and passing on well-being to future generations. The present study aimed to characterize the relationship between staff member generativity and perceived job competence in elderly nursing homes, and to determine the professional value of elderly care. METHODS: A total of 367 care staff at 13 nursing homes for elderly people participated in the present study, the design of which was a questionnaire survey. The survey addressed topics related to generativity and perceived job competence. Path analysis was conducted to examine the relationship between generativity and perceived job competence. RESULTS: Perceived job competence was related to age (ß=0.19, p<0.01) and occupational period (ß=0.14, p<0.05), and generativity was related to perceived job competence (ß=0.67, p<0.001). These results also suggest that perceived job competence promotes generativity development. CONCLUSIONS: The development of staff generativity in nursing homes may yield work satisfaction and elevated vocational identity.

Prediction of reactivity to noninherited maternal antigen in MHC-mismatched, minor histocompatibility antigen-matched stem cell transplantation in a mouse model.

The immunologic effects of developmental exposure to noninherited maternal Ags (NIMAs) are quite variable. Both tolerizing influence and inducing alloreaction have been observed on clinical transplantation. The role of minor histocompatibility Ags (MiHAs) in NIMA effects is unknown. MiHA is either matched or mismatched in NIMA-mismatched transplantation because a donor of the transplantation is usually limited to a family member. To exclude the participation of MiHA in a NIMA effect for MHC (H-2) is clinically relevant because mismatched MiHA may induce severe alloreaction. The aim of this study is to understand the mechanism of NIMA effects in MHC-mismatched, MiHA-matched hematopoietic stem cell transplantation. Although all offsprings are exposed to the maternal Ags, the NIMA effect for the H-2 Ag was not evident. However, they exhibit two distinct reactivities, low and high responder, to NIMA in utero and during nursing depending on the degree of maternal microchimerism. Low responders survived longer with less graft-versus-host disease. These reactivities were correlated with Foxp3 expression of peripheral blood CD4(+)CD25(+) cells after graft-versus-host disease induction and the number of IFN-γ-producing cells stimulated with NIMA pretransplantation. These observations are clinically relevant and suggest that it is possible to predict the immunological tolerance to NIMA.

Development of a dendritic cell vaccine against measles for patients following hematopoietic cell transplantation.

Most patients who have undergone hematopoietic cell transplantation (HCT) lose specific immunity to measles. However, due to its immunosuppressive potential, it has been recommended that a live attenuated measles vaccination be administered two years following HCT. Measles virus (MV) glycoproteins including hemagglutinin (HA) are expressed on MV-infected dendritic cells (DCs), and they impair efficient antigen presentation between the DC and T cell. We produced a DC-based vaccine against MV by loading DCs with MV-infected autologous DCs. MV in the infected DCs was inactivated using ultraviolet-B. The DC-based vaccine neither expressed HA nor inhibited allogeneic T cell proliferation, while it induced the production of interferon-gamma (IFN-gamma) by autologous CD4 and CD8 naive T cells ex vivo. Importantly, the vaccine derived from patients who had undergone HCT also efficiently induced IFN-gamma producing cells. These findings indicate that our DC-based MV vaccine induces MV-specific immunity even in post-HCT patients without causing immunosuppression.

Discrimination of acute graft-versus-host disease from infections by enumeration of peripheral blood interferon-gamma spot-forming cells.

Infections may coexist and in certain circumstances aggravate acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation. Early detection of aGVHD is often difficult in patients with concurrent infections. Using an enzyme-linked immunospot assay that reflects ongoing immune status in vivo, we enumerated spot-forming cells (SFCs) for interferon (IFN)-gamma, interleukin (IL)-4, and IL-12 in peripheral blood from 56 patients with hematological disorders. Eleven patients had viral, fungal, or bacterial systemic infections during first 10 weeks posttransplant. Of these, six patients with grade 0-I aGVHD showed normal levels of IFN-gamma SFCs. On the other hand, IFN-gamma SFCs were elevated in five patients with grade II-IV aGVHD. These data indicate that increased IFN-gamma SFCs seemed to be correlated with clinically significant aGVHD, but not with infection itself. IL-4 and IL-12 SFCs increased in some patients with infections, irrespective of the presence of aGVHD. Thus, IFN-gamma SFCs may be used to distinguish systemic infections from aGVHD.

Prediction of acute graft-versus-host disease and detection of distinct end-organ targets by enumeration of peripheral blood cytokine spot-forming cells.

BACKGROUND: Acute graft-versus-host disease (aGVHD) remains a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. It was hypothesized that type 1 cytokines promoted aGVHD and type 2 cytokines inhibited it. However, recent publications demonstrated contradictory results in murine models. Type 1/2 paradigm in aGVHD remains to be determined in human. METHODS: Using enzyme-linked immunospot assay that reflects ongoing immune status in vivo, we measured spot-forming cells (SFCs) for interferon (IFN)-gamma, interleukin (IL)-12, IL-4, and IL-10 in peripheral blood from 56 patients with hematological disorders who underwent allogeneic hematopoietic stem cell transplantation. RESULTS: The numbers of IFN-gamma and IL-4 SFCs in patients with grade II approximately IV aGVHD were significantly higher than those in patients with grade 0 approximately I aGVHD. The enumeration of cytokine SFCs predicted aGVHD approximately 4 days before it became clinically evident, since IFN-gamma SFCs in asymptomatic phase that later progressed into grade II approximately IV aGVHD were elevated in 8 out of 8 evaluable patients. Similarly, IL-4 SFCs were elevated in 6 of 8 patients. In addition, Type 1 cytokine SFCs contributed to the intestinal, but not skin and hepatic aGVHD. CONCLUSIONS: Enzyme-linked immunospot assay is clinically useful for predicting aGVHD and detecting distinct end-organ targets following allogeneic hematopoietic stem cell transplantation.