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Summary: A 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial (the TWICE study) conducted in Japanese primary osteoporosis patients with a high risk of fractures demonstrated that a 28.2-μg twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-μg once-weekly regimen of teriparatide, while also improving safety. Introduction: While a 56.5-μg once-weekly regimen of teriparatide has high efficacy for osteoporosis, treatment continuation rates are low, with one of the major causes being adverse drug reactions such as nausea or vomiting. The TWICE study was therefore conducted to investigate whether a twice-weekly regimen with 28.2-μg teriparatide can provide comparable efficacy to the 56.5-μg once-weekly regimen while improving safety. Methods: A 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial was conducted in Japan. Patients with primary osteoporosis aged ≥ 65 years at high risk of fractures (n = 553) were randomly allocated to the 28.2-μg twice-weekly group (n = 277) or the 56.5-μg once-weekly group (n = 276). The primary endpoint was the percentage change in lumbar spine (L2–L4) bone mineral density (BMD) at final follow-up. Results: The percentage changes in lumbar spine (L2–L4) BMD at final follow-up in the 28.2-μg twice-weekly and 56.5-μg once-weekly groups were 7.3% and 5.9%, respectively; the difference (95% confidence interval [CI]) in percentage change was 1.3% (0.400–2.283%). Since the lower limit of the 95% CI was above the pre-specified non-inferiority margin (− 1.6%), non-inferiority of the 28.2-μg twice-weekly group was demonstrated. Adverse drug reactions were significantly less frequent in the 28.2-μg twice-weekly group (39.7% vs 56.2%; p < 0.01); the incidence of major adverse drug reactions was lower, and the number of subjects who discontinued due to adverse drug reactions was less in the 28.2-μg twice-weekly group. Conclusions: A 28.2-μg twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-μg once-weekly regimen while improving safety. Clinical trial registration: JapicCTI-163477. [ABSTRACT FROM AUTHOR]

Mass mortality of fagaceous trees caused by Japanese oak wilt has occurred widely in Japan. Although virulence of the causal fungus, Raffaelea quercivora, appeared to differ among isolates, its relation to the fungal growth within trees was unknown. To clarify the differences in fungal virulence against susceptible Quercus crispula, we examined fungal growth of four R. quercivora isolates within trees and the resulting virulence. In our study, the isolates were multiple-inoculated in seedlings and single-inoculated in twigs of mature trees. In the multiple-inoculation test, mortality rates were examined by the observation of external symptoms. In the single-inoculation test, water conductance and hyphal growth within the trees were examined by applying aqueous dyes and fluorescence microscopy, respectively. Mortality rates, the proportion of the cross-sectional area comprising non-conductive sapwood and horizontal hyphal growth differed significantly among the isolates. Univariate logistic regression analyses showed that both the proportion of non-conductive sapwood and hyphal growth were significantly positively related to mortality rates. For three isolates, hyphal growth was significantly positively correlated with the proportion of non-conductive sapwood. These results suggested that the virulence against Q. crispula varies among R. quercivora isolates and that the extent of fungal colonization of the tree determines fungal virulence. [ABSTRACT FROM AUTHOR]

Summary: The MOVEST study evaluated the efficacy and safety of monthly oral ibandronate versus licensed monthly IV ibandronate in Japanese osteoporotic patients. Relative BMD gains after 12 months were 5.22 % oral and 5.34 % IV, showing non-inferiority of oral to IV ibandronate (primary endpoint). No new safety concerns were identified. Introduction: The randomized, phase 3, double-blind MOVEST (Monthly Oral VErsus intravenouS ibandronaTe) study evaluated the efficacy and safety of monthly oral ibandronate versus the licensed monthly intravenous (IV) ibandronate regimen in Japanese patients with osteoporosis. Methods: Ambulatory patients aged ≥55 years with primary osteoporosis were randomized to receive oral ibandronate 100 mg/month plus monthly IV placebo, or IV ibandronate 1 mg/month plus monthly oral placebo. The primary endpoint was non-inferiority of oral versus IV ibandronate with respect to bone mineral density (BMD) gains at the lumbar spine after 12 months of treatment. Results: Four hundred twenty-two patients were enrolled with 372 patients in the per-protocol set (183 and 189 in the oral and IV ibandronate groups, respectively). The relative change from baseline in lumbar spine BMD values for the oral and IV ibandronate groups, respectively, was 5.22 % (95 % confidence interval [CI] 4.65, 5.80) and 5.34 % (95 % CI 4.78, 5.90). The least squares mean difference between the two groups was −0.23 % (95 % CI −0.97, 0.51), showing non-inferiority of oral ibandronate to IV ibandronate (non-inferiority limit = −1.60). Changes in BMD values at other sites, and bone turnover marker levels in the oral ibandronate group, were comparable with those of the IV group. The safety profile was similar to that previously demonstrated; no new safety concerns were identified. Conclusions: This study demonstrated the non-inferiority of oral ibandronate 100 mg/month to IV ibandronate 1 mg/month (licensed dose in Japan) in increasing lumbar spine BMD in Japanese patients with primary osteoporosis. [ABSTRACT FROM AUTHOR]

Summary: Combined treatment with alendronate and eldecalcitol was found to be more effective in reducing the bone turnover markers and increasing bone mineral density than alendronate treatment with vitamin D3 and calcium supplementation in the osteoporotic patients. Introduction: We compared the clinical efficacy and safety of combined treatment with alendronate plus eldecalcitol (ALN + ELD) with those of treatment with ALN plus vitamin D and calcium (ALN + VitD). Methods: Osteoporotic 219 patients were randomly assigned to the ALN + ELD, or the ALN + VitD group. Primary endpoint was the inter-group differences in lumbar spine BMD (L-BMD) at patient's last visit. Secondary endpoints included the differences in BMD at other sites and the bone turnover marker (BTM) levels. Results: L-BMD, total hip BMD and femoral neck (FN-BMD) increased from baseline by 7.30, 2.41, and 2.70 % in the ALN + ELD group, and by 6.52, 2.27, and 1.18 % in the ALN + VitD group, respectively. Inter-group differences of the L-BMD and total hip BMD values were not significant. The increase of the FN-BMD was larger in the ALN + ELD group than the ALN + VitD group. Reductions of the BTMs were greater in the ALN + ELD group than the ALN + VitD group. Interaction of the percent increase of the L-BMD with the baseline values of the BTMs was observed in the ALN + VitD group only. The increases of the FN-BMD in patients with lower baseline values of type-I-collagen C-telopeptide (sCTX) and serum 25(OH) D levels <20 ng/mL were significantly larger in the ALN + ELD group than the other group. Conclusion: Combination treatment of ALN plus ELD was more effective in reducing the BTMs and increasing the FN-BMD than ALN treatment with vitamin D3 and calcium. [ABSTRACT FROM AUTHOR]

Summary: A 12-month extension phase of DIRECT in Japanese subjects with osteoporosis showed that total 3 years of denosumab treatment in Japanese postmenopausal women and men with osteoporosis was associated with low fracture rates, persistent bone turnover marker (BTM) reductions, continuous bone mineral density (BMD) increases, and a favorable overall benefit/risk profile. Introduction: The DIRECT trial demonstrated that 2 years of treatment with denosumab 60 mg subcutaneously every 6 months significantly reduced the incidence of vertebral fracture compared to placebo in Japanese postmenopausal women and men with osteoporosis. The purpose of this study is to evaluate the efficacy and safety of denosumab treatment for up to 3 years. Methods: This study includes a 2-year randomized, double-blind, placebo-controlled phase and a 1-year open-label extension phase in which all subjects received denosumab. The data correspond to 3 years of denosumab treatment in subjects who received denosumab (long-term group) and 1 year of denosumab treatment in subjects who received placebo (cross-over group) in the double-blind phase. Results: Eight hundred and ten subjects who completed the double-blind phase enrolled into the extension phase, and 775 subjects completed the study. All subjects received denosumab with daily supplements of calcium and vitamin D. The cumulative 36-month incidences of new or worsening vertebral fractures and new vertebral fractures were 3.8 and 2.5 %, respectively, in the long-term group. In this group, the BMD continued to increase, and the reduction in BTMs was maintained. In the cross-over group, comparable BMD increases and BTMs reductions to those of in their first year of the long-term group were confirmed. Adverse events did not show a notable increase with long-term denosumab administration. One event of osteonecrosis of the jaw occurred in the cross-over group. Conclusions: Three-year denosumab treatment in Japanese subjects with osteoporosis showed a favorable benefit/risk profile. [ABSTRACT FROM AUTHOR]

Summary: Once-weekly administration of 56.5 μg teriparatide improved cortical bone parameters and biomechanical parameters at the proximal femur by CT geometry analysis. Introduction: The aim of this study was to evaluate the effects of weekly administration of teriparatide [human PTH (1-34)] on bone geometry, volumetric bone mineral density (vBMD), and parameters of bone strength at the proximal femur which were longitudinally investigated using computed tomography (CT). Methods: The subjects were a subgroup of a recent, randomly assigned, double-blind study (578 subjects) comparing the anti-fracture efficacy of a once-weekly subcutaneous injection of 56.5 μg teriparatide with placebo (TOWER trial). Results: Sixty-six ambulatory postmenopausal women with osteoporosis were enrolled at 15 study sites having multi-detector row CT, and included women injected with teriparatide ( n = 29, 74.2 ± 5.1 years) or with placebo ( n = 37, 74.8 ± 5.3 years). CT data were obtained at baseline and follow-up scans were performed at 48 and 72 weeks. The data were analyzed to obtain cross-sectional densitometric, geometric, and biomechanical parameters including the section modulus (SM) and buckling ratio (BR) of the femoral neck, inter-trochanter, and femoral shaft. We found that once-weekly teriparatide increased cortical thickness/cross-sectional area (CSA) and total area, and improved biomechanical properties (i.e., decreasing BR) at the femoral neck and shaft. Teriparatide did not change the cortical perimeter. Conclusions: Our longitudinal analysis of proximal femur geometry by CT revealed that once-weekly administration of 56.5 μg teriparatide improved cortical bone parameters at the femoral neck and shaft and also improved biomechanical parameters. [ABSTRACT FROM AUTHOR]

Summary: We used quantitative computed tomography and finite element analysis to classify women with and without hip fracture. Highly accurate classifications were achieved indicating the potential for these methods to be used for subject-specific assessment of fracture risk. Introduction: Areal bone mineral density (aBMD) is the current clinical diagnostic standard for assessing fracture risk; however, many fractures occur in people not defined as osteoporotic by aBMD. Finite element (FE) analysis based on quantitative computed tomography (QCT) images takes into account both bone material and structural properties to provide subject-specific estimates of bone strength. Thus, our objective was to determine if FE estimates of bone strength could classify women with and without hip fracture. Methods: Twenty women with femoral neck fracture and 15 women with trochanteric fractures along with 35 age-matched controls were scanned with QCT at the hip. Since it is unknown how a specific subject will fall, FE analysis was used to estimate bone stiffness and bone failure load under loading configurations with femoral neck internal rotation angles ranging from −30° to 45° with 15° intervals. Support vector machine (SVM) models and a tenfold cross-validation scheme were used to classify the subjects with and without fracture. Results: High accuracy was achieved when using only FE analysis for classifying the women with and without fracture both when the fracture types were pooled (82.9 %) and when analyzed separately by femoral neck fracture (87.5 %) and trochanteric fracture (80.0 %). The accuracy was further increased when FE analysis was combined with volumetric BMD (pooled fractures accuracy, 91.4 %) Conclusions: While larger prospective studies are needed, these results demonstrate that FE analysis using multiple loading configurations together with SVM models can accurately classify individuals with previous hip fracture. [ABSTRACT FROM AUTHOR]

Pattern classification is very unique in traditional medicine. Kampo medical patterns have transformed over time during Japan's history. In the 17th to 18th centuries, Japanese doctors advocated elimination of the Ming medical theory and followed the basic concepts put forth by Shang Han Lun and Jin Gui Yao Lue in the later Han dynasty (25-220 AD). The physician Todo Yoshimasu (1702-1773) emphasized that an appropriate treatment could be administered if a set of patterns could be identified. This principle is still referred to as "matching of pattern and formula" and is the basic concept underlying Kampo medicine today. In 1868, the Meiji restoration occurred, and the new government changed its policies to follow that of the European countries, adopting only Western medicine. Physicians trained in Western medicine played an important role in the revival of Kampo medicine,modernizing Kampo patterns to avoid confusion with Western biomedical terminology. In order to understand the Japanese version of traditional disorders and patterns, background information on the history of Kampo and its role in the current health care system in Japan is important. In this paper we overviewed the formation of Kampo patterns. [ABSTRACT FROM AUTHOR]

Experienced peer support groups ( EPSG) are expected to improve self-care and complement professional health care for haemophilic patients, even those living in inconvenient clinical setting. However, these benefits have not been verified quantitatively. The structural equation modelling ( SEM) was used to evaluate the effects of contact with EPSG on self-care for haemophilic patients in the Japanese clinical settings. Factors affecting self-care were compared between groups with and without EPSG contact. Self-reported questionnaires were mailed to 652 haemophilic patients with HIV in Japan (September 2005-January 2006). SEM demonstrated significant associations between EPSG contact, self-care scores and other social and individual factors. The total effect of EPSG contact on self-care was calculated. The structural differences between models were analysed in a multi-group analysis. Of the 257 respondents (response rate, 39.4%), 109 reported having contact with an EPSG ( EPSG+ group) and 139 reported no contact ( EPSG− group). EPSG contact was significantly associated with better self-care. In the multi-group analysis, the total effect of inconvenient access to medical services on self-care in the EPSG+ group was 10% of that in the EPSG− group and was significantly associated with poor illness-related knowledge and high anxiety level only in the EPSG− group. In the EPSG+ group, patient age was strongly associated with self-care than in the EPSG− group. These findings suggest that EPSG contact may alleviate inconvenience in medical services. Factors associated with self-care differed between groups. Health care professionals must carefully assess self-care behaviours and service accessibility based on these results. [ABSTRACT FROM AUTHOR]

Summary: Monthly minodronate at 30 or 50 mg had similar efficacy as 1 mg daily in terms of change in bone mineral density (BMD) and bone turnover markers with similar safety profiles. This new regimen provides patients with a new option for taking minodronate. Introduction: Minodronate at a daily oral dose of 1 mg has been proven to have antivertebral fracture efficacy. In the present study, the efficacy and safety of oral minodronate at monthly doses of either 30 mg or 50 mg were compared with a daily dose of 1 mg. Methods: A total of 692 patients with involutional osteoporosis were randomized to receive minodronate at either 30 or 50 mg monthly or a daily dose of 1 mg. The primary endpoint was the percent change from baseline in lumbar spine (LS) BMD at 12 months. Total hip BMD, bone turnover markers, serum calcium (Ca), and parathyroid hormone (PTH) levels were also evaluated. Results: Minodronate at monthly doses of 30 or 50 mg were noninferior to the 1 mg daily dose in terms of change in LS-BMD. Changes in total hip BMD were also comparable. Although a transient decrease in serum Ca and increase in PTH levels were observed in all three groups at slightly different magnitudes and time courses, changes in bone turnover markers were comparable among the different dosage groups with a similar time course. Safety profiles were also comparable. Conclusion: Minodronate at monthly doses of 30 or 50 mg has similar efficacy to the daily 1 mg dose in terms of BMD and bone turnover markers with similar tolerability. [ABSTRACT FROM AUTHOR]

Long columns of migrating larval sciarid armyworms were discovered in central and northern Japan, specifically Kanagawa, Gunma, Miyagi and Akita prefectures, as well as Hokkaido. This is the first examination of armyworms in East Asia. In Europe, armyworms have been identified as Sciara militaris, belonging to the family Sciaridae (sciarid flies or black fungus gnats), by rearing them to adulthood. In Japan, we were unable to obtain live samples for rearing; therefore, DNA barcodes were obtained from the samples of armyworms collected in the Gunma and Miyagi prefectures. The DNA barcodes were compared with those obtained from the following samples: pupae of S. militaris from UK, adults of Sciara kitakamiensis, Sciara humeralis, Sciara hemerobioides, Sciara thoracica, Sciara helvola and Sciara melanostyla from Japan, and adults of one undescribed Sciara species from Malaysia. Neighbour-joining, maximum parsimony, and maximum likelihood analyses revealed that the armyworms discovered in Japan are S. kitakamiensis. Although adults of this species have been recorded in several locations in Japan, this is the first report of migrating larval armyworms. DNA barcodes were effectively used to link different life stages of this species. The average intraspecific and interspecific pairwise genetic distances of the genus Sciara were 0.3% and 12.6%, respectively. The present study illustrates that DNA barcodes are an effective means of identifying sciarid flies in Japan. [ABSTRACT FROM AUTHOR]

Summary: Bone mineral density (BMD) of the lumbar spine, ultradistal radius, and calcaneus were significantly higher in the developmental dysplasia of the hip (DDH) patients than in the controls. Therefore, our data suggest that BMDs at different skeletal sites are greater in patients with DDH than in healthy women. Introduction: DDH has been acknowledged as a potentially preosteoarthritic condition that results in the development of hip osteoarthritis. Patients with DDH have been reported to have abnormal morphology of the pelvis and spine. Additional research, including that of bone quality, needs to be conducted to elucidate the pathogenetic mechanism of this disease. We therefore sought to determine whether BMD differs between healthy women and women with DDH. Methods: We measured BMD in 40 women who were scheduled to undergo pelvic osteotomy for DDH (average age, 45.3 years) and in 31 healthy women used as age-matched controls (average age, 47.5 years). BMDs of the lumbar spine, radius, and calcaneus were measured. Results: BMDs of the lumbar spine, ultradistal radius, and calcaneus were significantly higher in the DDH patients than in the controls. Conclusions: Therefore, our data suggest that BMDs at different skeletal sites are greater in patients with DDH than in healthy women. [ABSTRACT FROM AUTHOR]

Internationally, nurses and physicians are increasingly expected to undertake roles in communication and patient advocacy, including in Japan, where the reigning principle underlying medical ethics is in transition from paternalism to respect for patient autonomy. The study reports the results of a survey in two Japanese teaching hospitals that clarified the perspectives of 128 patients and 41 family members regarding their current and desired involvement in health decision-making. The commonest process that was desired by patients and their family was for patients to make decisions after consultation with both the physician and their family. The decision-making preferences for competent patients varied among the participants, who believed that families have a crucial role to play in health-care decision-making, even when patients are competent to make their own decisions. The findings will inform health professionals about contemporary Japanese health-care decision-making and the ethical issues involved in this process, as well as assist the future development of a culturally relevant model to support patients' preferences for ethical decision-making. [ABSTRACT FROM AUTHOR]

Background Few studies have compared the efficacy of proton pump inhibitors in resolving the symptoms of non-erosive reflux disease (NERD) and of erosive gastro-oesophageal reflux disease (GERD) in Japan. Aim To investigate and compare the efficacy of 4-week course of rabeprazole 10 mg/day on symptom resolution in NERD and erosive GERD in Japan. Methods The modified Los Angeles classification was used to grade endoscopically GERD in patients with heartburn (Grades N and M: NERD, Grades A and B: mild reflux oesophagitis (RO), and Grades C and D: severe RO). Rabeprazole 10 mg/day was administered for 4 weeks to 180 patients who kept symptom diaries. Results Complete relief of the symptoms was achieved in 35.8% of the NERD group and 55.4% of the erosive GERD group (mild RO: 51.1% and severe RO: 77.8%). Rabeprazole was significantly more effective in erosive GERD than in NERD patients. Among the NERD subgroups (Grades N and M), no difference in symptom improvement was observed. Conclusions Four-week, rabeprazole 10 mg/day acid suppression therapy was effective in resolving symptoms in Japanese GERD patients. This therapy was more effective in erosive GERD than in NERD patients, and in those with severe RO than in those with mild RO. [ABSTRACT FROM AUTHOR]

Areas infested with Solanum carolinense, an introduced perennial weed, have increased quickly in Japan. The genetic structure of a S. carolinense population along the Takano River in Kyoto, Japan was investigated using amplified fragment length polymorphism (AFLP) analysis to reveal how introductions and local spread have contributed to the development of this population. Along a terrace beside the river and an adjacent roadside, we defined a cluster of above-ground shoots in the population as a subpopulation and 60 subpopulations were identified. Seventeen of these were selected and 165 shoots were analyzed by AFLP analysis using three primer pairs. The AFLP profiles revealed 69 genotypes and the presence of several clones, i.e. genotypes that were present in more than one individual. In total, 19 clones, comprising 2–34 identical genotypes, could be identified in the population. Each of these clones, except one, was allocated within each of the subpopulations. Clustering of the subpopulations was supported by high bootstrap values in all cases. Therefore, introductions from distant regions have mainly contributed to the development of this population, and local spread by seed or vegetative reproduction has rarely been important. The most likely introduction route of S. carolinense to this population was via planting associated with construction works. [ABSTRACT FROM AUTHOR]

A multicentre study on the epidemiology of perinatal depression was conducted among Japanese women expecting the first baby (N = 290). The incidence rate of the onset of the DSM-III-R Major Depressive Episode during pregnancy (antenatal depression) and within 3 months after delivery (postnatal depression) were 5.6% and 5.0%, respectively. Women with antenatal depression were characterised by young age and negative attitude towards the current pregnancy, whereas women with postnatal depression were characterised by poor accommodation, dissatisfaction with sex of the newborn baby and with the emotional undermining. Antenatal depression was a major risk factor for postnatal depression. [ABSTRACT FROM AUTHOR]

Aim: This study was conducted to explore the meaning of health for Japanese elders who have had a stroke.Methods: A secondary analysis of existing data was conducted by using phenomenological methods. Twenty-four male and female stroke patients, whose average age was 76 +/- 7.2 years, described the meaning of health with one researcher. Researchers from Japan and the USA analysed the data through email communication and scheduled visits. The five-step analysis method began from the English transcriptions of descriptions to finally identify a structural definition of health for Japanese elders who have had a stroke.Results: The structural definition identifies health as a fundamentally valuable gift recognized by stroke patients as they try to adjust to their present circumstance, defined by their past experience, and as they consider dimensions of everyday living from a new perspective. Judgments about how they are doing are created through the eyes and expressions of others who interact with them and through everyday markers of usual life, like a good appetite, easy breathing and smooth thinking and moving.Conclusions: Comparable with other studies, elderly Japanese stroke survivors seek a revised but familiar, stable 'self' based on a new frame of reference incorporating their past with the person they are now. Unlike other stroke survivors of previous studies, these Japanese elders considered fundamental human patterns such as breathing and eating as markers for good health, and they used the assessments of others to judge their progress. There is a need for health-care providers to thoughtfully engage with stroke survivors to determine the most meaningful approaches to care and engagement demands and understand that their interactions are intricately woven into the patient's health experience. [ABSTRACT FROM AUTHOR]

Summary Aim : To investigate whether curing Helicobacter pylori infection improves symptoms over the long-term in Japanese patients with nonulcer dyspepsia and fundic atrophic gastritis. Methods : Ninety H. pylori -positive dyspeptic patients with fundic atrophic gastritis were enrolled in this study. We performed a randomized double-blind placebo-controlled trial comparing triple therapy (n = 45) with that of placebo alone (n = 45). Inflammation and mucosal atrophy were scored according to the Updated Sydney System. Symptoms were scored on a scale of 0 to 3 for six items. Fasting samples of gastric juice were taken before endoscopy, and gastric pH was determined. Serum gastrin and pepsinogen levels were measured, and body mass index was determined. These patients were followed up for 3 years, and all measures were evaluated both before and after therapy. Results : Significant improvement in dyspeptic symptoms and gastritis scores, significant decrease in gastric pH, and significant increase in body mass index were found after 3 years eradication in nonulcer dyspepsia patients treated successfully for H. pylori infection. There were no significant changes in the placebo group. Conclusion : Our study shows that eradicating of H. pylori results in significant long-term reduction in symptoms of nonulcer dyspepsia with fundic atrophic gastritis. [ABSTRACT FROM AUTHOR]

This survey study measured the communication effectiveness of 176 nurses working on a variety of clinical units within one large university hospital in western Japan. The vast majority of the nurses demonstrated fair effectiveness in their communication skills. Although some of the nurses did demonstrate slightly higher communication effectiveness scores, few of the nurses' demographic characteristics appeared to influence how well they communicated. The major limitations of the present study were the use of one hospital for data gathering, and the possible lack of cultural sensitivity of the communication questionnaire. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori plays an important part in the progression of atrophic gastritis; however, markers for predicting the progression of atrophic gastritis remain unidentified. We investigated the relation between the degree of atrophic gastritis and the amount of anti-parietal cell antibodies (APCAs) present. Methods: In 219 Japanese patients, APCA was investigated by enzyme-linked immunosorbent assay (ELISA) and by Western blotting. The grade of corpus atrophy was estimated by histology and serum pepsinogen levels. Serum levels of pepsinogen were evaluated by radio-immunoassay. Results: Helicobacter pylori infection did not affect the APCA levels determined by ELISA. Long-term administration of proton-pump inhibitors and H. pylori eradication did not influence the levels of APCAs. However, in H. pylori-positive patients, the levels of APCA determined by ELISA were statistically higher in patients with severe atrophy than in those with mild atrophy as determined histologically (0.67 ± 0.48 versus 0.45 ± 0.40; A492, mean ± s, P = 0.01) and serologically by pepsinogen levels (0.66 ± 0.51 versus 0.44 ± 0.40, P = 0.002). The levels of pepsinogen I/II ratio were correlated with APCA levels only in the H. pylori-positive group. Western blotting showed that major antigen was identical with the β-subunit of H+,K+-ATPase. Conclusion: APCA plays an important part in the progression of corpus atrophy after H. pylori infection. [ABSTRACT FROM AUTHOR]

Scrotal calcinosis has been classified as a form of idiopathic calcinosis cutis. However, the pathogenesis of the calcified nodules has not been fully elucidated: it is still unclear whether the condition is truly idiopathic, or the result of breakdown of calcified epithelial cysts. We describe a 29-year-old Japanese patient with scrotal calcinosis originating from epithelial cysts. Light microscopy revealed a large epithelial cyst containing von Kossa-positive material and several small dilated ductal structures beside the cyst. The epithelia of the cyst and ductal structures were connected, showing similar eccrine duct differentiation on immunohistochemical staining and electron microscopy. In the cyst lumen, calcium was present as needle-shaped crystals. The pathogenetic mechanism of calcium deposition seemed to be due to excessive production and discharge of matrical debris and sulphated mucopolysaccharides, which derived from luminal cells, and their accumulation in the lumina. [ABSTRACT FROM AUTHOR]

SummaryBackground: Hepatic artery thrombosis after liver transplantation remains a significant cause of graft loss and death. Retransplantation is a difficult option after living-related liver transplantation in Japan. Methods: Twenty-seven patients underwent living-related liver transplantation with left-sided liver grafts donated from their relatives. The hepatic artery was anastomosed end to end under a surgical microscope. Anticoagulant therapy was maintained for 2 weeks after operation. Routine post-transplant Doppler ultrasonography together with serum blood tests were performed twice a day during the first 2 weeks. Results: Three patients developed hepatic artery occlusion, which was identified by routine Doppler ultrasonography before the serum transaminase values increased on days 7, 7 and 3 after surgery respectively. In two of the three patients, no apparent arterial thrombosis was recognized and vasospasm was therefore considered to be the cause of the occlusion. Arterial patency was restored by urgent revascularization with reanastomosis in all patients, but one patient with a functional graft died from a cerebral haemorrhage on day 47. Conclusion: Early diagnosis of hepatic artery occlusion by routine Doppler ultrasonography and revascularization of the graft is an indispensable strategy for preventing graft loss after living-related liver transplantation. [ABSTRACT FROM AUTHOR]

The article discusses asymmetric palladium catalysis by using ion-paired chiral ligands. It mentions that ion pair composed of an achiral ammonium-phosphine and a chiral binaphtholate ion acts as an efficient chiral ligand for palladium-catalyzed asymmetric allylic alkylation of alpha-nitro carboxylates. It informs that the strategy was developed by Takashi Ooi, professor at the Department of Applied Chemistry at the Graduate School of Engineering of Nagoya University in Japan.

Clin Microbiol Infect 2012; 18: 260-267 Abstract Japanese spotted fever (JSF) is caused by Rickettsia japonica, and lethal cases are reported yearly in southwest Japan. We thus established the method of diagnosing JSF by immunohistochemistry (IHC) and real-time PCR (RT-PCR) using formalin-fixed, paraffin-embedded skin biopsy specimens. Two monoclonal antibodies were used for IHC, and the 17k genus common antigen gene served as the target of RT-PCR. We collected skin biopsy ( n = 61) and autopsy ( n = 1) specimens from 50 patients clinically suspected of JSF. Immunohistochemically, the rickettsial antigens were localized as coarse dots in the cytoplasm of endothelial cells and macrophages. Thirty-one seropositive cases plus one autopsy case (group A) and nine seronegative cases but with positive IHC and/or RT-PCR (group B) were judged as JSF. Nine cases were regarded as non-JSF disorders based on negative serology, IHC and RT-PCR (group C). Of 50 biopsies (eschar 34, eruptions 10, and scabs 6) from groups A and B, IHC and RT-PCR positivities were 94% (32/34) and 62% (21/34) for eschar, 80% (8/10) and 30% (3/10) for eruptions, and 33% (2/6) and 50% (3/6) for scabs. For IHC, eschar was most suitable, and scabs were insufficient. Unexpectedly, 18 biopsies happened to be fixed in 100% formalin, and this lowered the detection rate by RT-PCR, but IHC was tolerant. Sequence analysis using five skin biopsy specimens confirmed a 114 bp DNA stretch homologous to that reported for the target gene of R. japonica. In 26 (84%) of the 31 seropositive patients, the diagnosis was made by IHC and/or RT-PCR earlier than serology. [ABSTRACT FROM AUTHOR]

Abstract: A lot of even and uneven settlement is expected to occur due to the heavy weight of the buildings and shields located at the Materials and Life Science Experimental Facility (MLF) and in the proton beam line (3NBT) that runs from the 3GeV Rapid-Cycling Synchrotron (RCS) to the neutron target at the Japan Proton Accelerator Research Complex (J-PARC). Because of this, and in order to achieve the necessary alignment of less than 1mm in precision, the settlement that has occurred with the MLF building and the 3NBT tunnel has been periodically surveyed (level measurement) since June 2004 until now when the MLF building has been completed. The survey results were used in determining the levels at which the beam line components were installed. The survey results indicated that the values of the settlement that had taken place were almost proportional to the located weight and could be used in estimating the settlement that would take place in the future. These results were reflected in the alignment of the proton and beam line components. [Copyright &y& Elsevier]

In the Solar System, extra-terrestrial organic molecules have been found on cometary primitive objects, on Titan and Enceladus icy moons and on Mars. Identification could be achieved for simple organic species by remote sensing based on spectroscopic methods. However in situ mass spectrometry is a key technology to determine the nature of more complex organic matter. A large panel of mass spectrometers has already been developed for space exploration combining different types of analysers and ion sources. Up to now the highest mass resolution reached with a space instrument is 9000 at m/z 28 and corresponds to the DFMS-ROSINA instrument (Balsiger et al., 2007) dedicated to the study of the comet 67P/Churyumov-Gerasimenko's atmosphere and ionosphere, in a low pressure environment. A new concept of mass analyser offering ultra-high mass resolving power of more than 50,000 at m/z 56 (under high vacuum condition about 10−9 mbar) is currently being developed for space applications: the CosmOrbitrap (Briois et al., 2016), based on the Orbitrap™ technology. This work challenges the use of LAb-CosmOrbitrap, a space instrument prototype combining Laser Ablation ionisation and the CosmOrbitrap mass analyser, to identify solid organic molecules of relevance to the future space exploration. For this purpose a blind test was jointly organised by the JAXA-HRMS team (Japan Aerospace Exploration Agency-High Resolution Mass Spectrometry) and the CosmOrbitrap consortium. The JAXA team provided two organic samples, whereas the CosmOrbitrap consortium analysed them without prior information. Thanks to the high analytical performances of the prototype and our HRMS data post-processing, we successfully identified the two molecules as HOBt, hydroxybenzotriazole (C 6 H 5 N 3 O) and BBOT, 2,5-Bis(5-tert-butyl-benzoxazol-2-yl)thiophene (C 26 H 26 N 2 O 2 S), with a mass resolving power of, respectively, 123 540 and 69 219. The success of this blind test on complex organic molecules shows the strong potential of LAb-CosmOrbitrap for future space applications. • Efficient ionisation of solid sample by nano-pulsed single laser shot. • Powerful analytical performances of CosmOrbitrap mass analyser. • Successful blind test identification of organics ionised by Laser-CosmOrbitrap. • Laser-CosmOrbitrap relevant technique for space exploration of organic rich worlds. [ABSTRACT FROM AUTHOR]

Serotype 23B Streptococcus pneumoniae was isolated from a 67-year-old Japanese patient with meningitis. This isolate was susceptible to penicillin G, while genotyped as gPISP with a mutation in a penicillin-binding motif in PBP2b. The 23B isolate was assigned to ST11996 that is related to CC439, a dominant group among serotype 23B. [ABSTRACT FROM AUTHOR]

We present the case of a 58-year-old female patient with primary ciliary dyskinesia (PCD). She was born to parents with a consanguineous marriage. Chest computed tomography conducted at age 41 years indicated no situs inversus, and findings of bronchiectasis were limited to the middle and lingular lobes. Despite long-term macrolide therapy, bronchiectasis exacerbations frequently occurred. PCD was suspected because of the low nasal nitric oxide level (20.7 nL/min). Electron microscopy revealed outer and inner dynein arm defects, and a genetic analysis identified a homozygous single-nucleotide deletion in the DNAAF1 gene. Based on these results, the patient was diagnosed with PCD due to a biallelic DNAAF1 mutation.

COVID-19 pandemic has had a substantial effect on healthcare systems worldwide, including the care of patients with lung cancer. The impact of healthcare disruptions and behavioral changes on lung cancer mortality is unclear. Patients newly diagnosed with lung cancer during the pandemic period 2020-2021 were compared with those diagnosed in the pre-pandemic 2018-2019. The primary outcome was all-cause mortality within 1 year. Cox proportional hazards regression analyses were conducted to estimate the changes in mortality between pandemic and pre-pandemic. Multiple mediation analyses were performed to determine the factors that accounted for the changes in mortality. In total, 5785 patients with lung cancer were included in this study. The overall mortality rate was significantly higher during the pandemic compared with the pre-pandemic (crude hazard ratio [HR]: 1.19, 95% confidence interval [CI]: 1.05, 1.29). Mediation analyses showed that not receiving tumor-directed treatment, diagnosis at an older age, and decreased diagnosis through cancer screening significantly accounted for 17.5% (95%CI: 4.2, 30.7), 13.9% (95%CI: 0.8, 27.0), and 12.4% (95%CI: 3.0, 21.8) of the increased mortality, respectively. This study revealed a significant increase in mortality risk in patients with lung cancer who have not received tumor-directed treatment or cancer screening, despite potential selection bias for follow-up status. Efforts should be focused on ensuring timely access to healthcare services, optimizing treatment delivery, and addressing the unique challenges faced by patients with lung cancer during the pandemic to mitigate the impact of the pandemic on lung cancer outcomes and provide clinical care to vulnerable populations., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background and Aims: Previous genome-wide association studies (GWAS) have indicated the involvement of shared (population-nonspecific) and nonshared (population-specific) susceptibility genes in the pathogenesis of primary biliary cholangitis (PBC) among European and East-Asian populations. Although a meta-analysis of these distinct populations has recently identified more than 20 novel PBC susceptibility loci, analyses of population-specific genetic architecture are still needed for a more comprehensive search for genetic factors in PBC., Approach and Results: Protein tyrosine phosphatase nonreceptor type 2 ( PTPN2) was identified as a novel PBC susceptibility gene locus through GWAS and subsequent genome-wide meta-analysis involving 2181 cases and 2699 controls from the Japanese population (GWAS-lead variant: rs8098858, p = 2.6 × 10 -8 ). In silico and in vitro functional analyses indicated that the risk allele of rs2292758, which is a primary functional variant, decreases PTPN2 expression by disrupting Sp1 binding to the PTPN2 promoter in T follicular helper cells and plasmacytoid dendritic cells. Infiltration of PTPN2-positive T-cells and plasmacytoid dendritic cells was confirmed in the portal area of the PBC liver by immunohistochemistry. Furthermore, transcriptomic analysis of PBC-liver samples indicated the presence of a compromised negative feedback loop in vivo between PTPN2 and IFNG in patients carrying the risk allele of rs2292758., Conclusions: PTPN2 , a novel susceptibility gene for PBC in the Japanese population, may be involved in the pathogenesis of PBC through an insufficient negative feedback loop caused by the risk allele of rs2292758 in IFN-γ signaling. This suggests that PTPN2 could be a potential molecular target for PBC treatment., (Copyright © 2024 American Association for the Study of Liver Diseases.)

This retrospective cohort study aimed to investigate the association between alcohol consumption and the onset of type 2 diabetes in middle-aged Japanese individuals. Participants were aged 40 and above from Panasonic Corporation, Osaka, Japan's medical health checkup program from 2008 to 2021. Alcohol consumption was calculated by converting the quantity consumed into daily ethanol consumption. We assessed the association between alcohol consumption and the onset of type 2 diabetes using Cox regression analysis. The total and median follow-up duration was 13 years and 7 (3-13) years (748,090 person-years). Among 102,802 participants, 7,510 participants (7.3%) developed type 2 diabetes during the study period. Alcohol consumption at the level of 0 < to < 22 g/day and 22 to < 39 g/day were negatively associated with developing type 2 diabetes compared to complete alcohol abstainers. Alcohol consumption at levels of 39 to < 66 g/day and at levels of ≥ 66 g/day were positively associated with developing type 2 diabetes in participants with BMI < 25 kg/m 2 . All levels of alcohol consumption were negatively associated with developing type 2 diabetes in participants with BMI ≥ 25 kg/m 2 . Moderate-to-heavy alcohol consumption were positively associated with developing type 2 diabetes for participants with BMI < 25 kg/m 2 , whereas alcohol intake was negatively associated with developing type 2 diabetes among participants with BMI ≥ 25 kg/m 2 ., (© 2024. The Author(s).)

Psossibility and appropriate timing of discontinuation of dupilumab for atopic dermatitis (AD) remain unclear. We explored the possibility of patients, who could maintain remission with topical therapy alone after withdrawing dupilumab in the real world. Furthermore, we identified their characteristics. All adult AD patients who initiated dupilumab from June 2018 to July 2022 and were treated with dupilumab for more than 3 months at our hospital were included in this study. The observation period was from June 2018 to July 2023. In 138 patients, 58 (42.0%) discontinued dupilumab at least once. Among them, 18 (13.0%) discontinued dupilumab but reinitiated dupilumab later due to exacerbation. Only seven patients (5.1%) could maintain remission with topical therapy alone after discontinuation of dupilumab, with characteristics of lower POEM, VAS of pruritus, serum levels of TARC and LDH, and neutrophil counts at baseline, and those of longer duration of dupilumab until its discontinuation (24.0 ± 13.3 vs. 12.8 ± 7.3 months) and lower EASI and affected BSA at the discontinuation of dupilumab. In 118 patients treated with dupilumab for at least 1 year, 38 patients (32.2%) discontinued at least once. Only four patients (3.4%) could maintain remission with topical therapy alone after discontinuation of dupilumab, with characteristics of lower POEM at baseline and lower EASI at the discontinuation of dupilumab. In conclusion, maintaining remission after withdrawing dupilumab is challenging. Discontinuation of dupilumab may be considered in patients with low baseline POEM, after more than 2 years of dupilumab treatment, with a substantial decrease in EASI., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Menthae Herba is an herbal medicine whose name is written with the same kanji characters () in both the Japanese Pharmacopoeia, 18th Edition (JP) and in the Pharmacopoeia of the People's Republic of China (CP). However, the original plant are Mentha arvensis Linné var. piperascens Malinvaud in JP and Mentha haplocalyx Briq. in CP. To clarify the similarities and differences between Menthae Herba in Japan and that in China, morphological observations, essential oil component analysis, and DNA analysis were performed on marketed products of Menthae Herba in Japan and in China. The morphological observations based on the description of JP Menthae Herba showed that most of the samples matched the items listed in the description. Essential oil component analysis by gas chromatography-mass spectrometry showed that the amount of menthol varied among samples and that menthol was not always the principal compound in the oil. The original plant species was confirmed by DNA analysis of the rpl16 intron region in chloroplast DNA and all samples matched the sequence of M. canadensis. The results showed that Menthae Herba products distributed in both Japan and China contained M. canadensis, but they had different compositions of essential oil, with menthol-rich Menthae Herba being dominant in the Japanese market., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Background and Objectives: In Japan, cord blood transplantations exceed those done with adult-sourced unrelated stem cells. This study analyses cord blood (CB) storage criteria to maintain high-quality CB units., Materials and Methods: The Kanto-Koshinetsu Cord Blood Bank received 29,795 units from 2014 to 2021, mostly >60 mL, and 5486 (18.4%) were stored as transplantable units. We investigated the mother's gestational period, CB volume, total nucleated cells (TNCs), CD34+ cells, total colony-forming units (CFUs), time from collection to reception and cryopreservation, cell viability, and the reasons for not storing a unit., Results: The average time from collection to reception of 29,795 units was 18.0 h. The most common reason for not storing a CB unit was low cell numbers (pre-processing TNC count <1.2 billion), accounting for 67.9% of the units received. There was no correlation between the CB volume and the CD34+ cell count. The shorter the gestational period, the lower the TNC count, but the higher the CD34+ cell count. There was no correlation between the time from collection to cryopreservation, within a 36-h time limit, and the CD34+ cell recovery rate., Conclusion: We could accept units with a TNC count <1.2 billion and a CB volume <60 mL from a gestational period of 38 weeks or less if we did a pre-processing CD34+ cell count. This would secure more units rich in CD34+ cells., (© 2024 International Society of Blood Transfusion.)

Background: Granulocyte colony-stimulating factor (G-CSF) is an essential supportive agent for chemotherapy-induced severe myelosuppression. We proposed two clinical questions (CQ): CQ #1, "Does primary prophylaxis with G-CSF benefit chemotherapy for non-round cell soft tissue sarcoma (NRC-STS)?" and CQ #2, "Does G-CSF-based intensified chemotherapy improve NRC-STS treatment outcomes?" for the Clinical Practice Guidelines for the Use of G-CSF 2022 of the Japan Society of Clinical Oncology., Methods: A literature search was performed on the primary prophylactic use of G-CSF for NRC-STSs. Two reviewers assessed the extracted papers and analyzed overall survival, incidence of febrile neutropenia, infection-related mortality, quality of life, and pain., Results: Eighty-one and 154 articles were extracted from the literature search for CQs #1 and #2, respectively. After the first and second screening, one and two articles were included in the final evaluation, respectively. Only some studies have addressed these two clinical questions through a literature review., Conclusion: The clinical questions were converted to future research questions because of insufficient available data. The statements were proposed: "The benefit of primary G-CSF prophylaxis is not clear in NRC-STS" and "The benefit of intensified chemotherapy with primary G-CSF prophylaxis is not clear in NRC-STSs." G-CSF is often administered as primary prophylaxis when chemotherapy with severe myelosuppression is administered. However, its effectiveness and safety are yet to be scientifically proven., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Aim/introduction: This historical cohort study sought to research the relationship between eating behaviors and the incidence of type 2 diabetes in a large, long-term cohort of Japanese subjects., Materials and Methods: Panasonic Corporation employees who had no history of diabetes and attended yearly health surveys between 2008 and 2018 were included in this study. The main outcome measure was diabetes onset., Results: This study included 128,594 participants and 6,729 participants who developed type 2 diabetes in the study period. Skipping breakfast, fast eating, snacking after dinner, and eating meals before sleeping were linked with the risk of the incidence of type 2 diabetes. In individuals with a BMI < 25 kg/m 2 , fast eating (hazard ratio [HR]: 1.61, 95% confidence interval [CI]: 1.37-1.90), and eating meals before sleeping (HR: 1.09, 95% CI: 1.02-1.17) were likewise associated with an increased risk of incident type 2 diabetes. Nevertheless, fast eating (HR: 1.08, 95% CI: 0.89-1.30) and meals before sleeping (HR: 0.94, 95% CI: 0.88-1.01) were not related to the occurrence of type 2 diabetes in individuals with a BMI ≥25 kg/m 2 (P value for interaction = 0.0007 [fast eating] and 0.007 [meals before sleeping], respectively). No significant interaction effect between sex and eating behavior was found., Conclusions: With respect to Japanese people, especially in people with a BMI < 25 kg/m 2 , eating behaviors may be a risk factor for the occurrence of type 2 diabetes., (© 2024 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: Multidrug chemotherapy for Ewing sarcoma can lead to severe myelosuppression. We proposed two clinical questions (CQ): CQ #1, "Does primary prophylaxis with G-CSF benefit chemotherapy for Ewing sarcoma?" and CQ #2, "Does G-CSF-based intensified chemotherapy improve Ewing sarcoma treatment outcomes?"., Methods: A comprehensive literature search was conducted in PubMed, Cochrane Library, and Ichushi web databases, including English and Japanese articles published from 1990 to 2019. Two reviewers assessed the extracted papers and analyzed overall survival (OS), febrile neutropenia (FN) incidence, infection-related mortality, quality of life (QOL), and pain., Results: Twenty-five English and five Japanese articles were identified for CQ #1. After screening, a cohort study of vincristine, ifosfamide, doxorubicin, and etoposide chemotherapy with 851 patients was selected. Incidence of FN was 60.8% with G-CSF and 65.8% without; statistical tests were not conducted. Data on OS, infection-related mortality, QOL, or pain was unavailable. Consequently, CQ #1 was redefined as a future research question. As for CQ #2, we found two English and five Japanese papers, of which one high-quality randomized controlled trial on G-CSF use in intensified chemotherapy was included. This trial showed trends toward lower mortality and a significant increase in event-free survival for 2-week interval regimen with the G-CSF primary prophylactic use compared with 3-week interval., Conclusion: This review indicated that G-CSF's efficacy as primary prophylaxis in Ewing sarcoma, except in children, is uncertain despite its common use. This review tentatively endorses intensified chemotherapy with G-CSF primary prophylaxis for Ewing sarcoma., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Bronchopulmonary dysplasia (BPD) has a lasting effect on the respiratory function of infants, imposing chronic health burdens. BPD is influenced by various prenatal, postnatal, and genetic factors. This study explored the connection between BPD and home oxygen therapy (HOT), and then we examined the association between HOT and a specific single-nucleotide polymorphism (SNP) in the hyaluronan and proteoglycan link protein 1 ( HAPLN1 ) gene among premature Japanese infants., Materials and Methods: Prenatal and postnatal data from 212 premature infants were collected and analyzed by four SNPs (rs975563, rs10942332, rs179851, and rs4703570) around HAPLN1 using the TaqMan polymerase chain reaction method. The clinical characteristics and genotype frequencies of HAPLN1 were assessed and compared between HOT and non-HOT groups., Results: Individuals with AA/AC genotypes in the rs4703570 SNP exhibited significantly higher HOT rates at discharge than those with CC homozygotes (odds ratio, 1.20, 95% confidence interval, 1.07-1.35, p  = .038). A logistic regression analysis determined that CC homozygotes in the rs4703570 SNP did not show a statistically significant independent association with HOT at discharge., Conclusions: Although our study did not reveal a correlation between HAPLN1 and the onset of BPD, we observed that individuals with CC homozygosity at the rs4703570 SNP exhibit a reduced risk of HOT.

Growing concerns have emerged over the combined effects of multiple stressors on ecosystems. Empirical evidence shows that the sensitivity of aquatic invertebrates to insecticides varies under thermally fluctuating conditions. Additionally, field surveys in estuarine areas of western Japan confirmed the presence of juvenile kuruma prawns (Penaeus japonicus) carrying the white spot syndrome virus (WSSV). Given the potential of co-exposure to multiple stressors, we performed a combined exposure experiment using a full-factorial design with three stressors: WSSV infection (presence or absence: initial 2 h exposure), fipronil (insecticide) exposure (0 or 0.1 μg/L: 14 d exposure), and temperature (20, 25, or 30 °C). We observed the highest mortality (75 %) in the WSSV + Fipronil treatment at 30 °C, with the associated specimens showing significant changes in the internal load of WSSV and concentrations of fipronil and its metabolite, fipronil sulfone. Severe perturbations of metabolites associated with increased energy expenditure and fatty acid utilization have been identified as potential factors underlying lethality in juvenile kuruma prawns. The results demonstrate that WSSV infection increases the susceptibility of thermally stressed juvenile kuruma prawns to fipronil. Therefore, further studies are required to determine the combined effects of multiple stressors in environmentally relevant scenarios on juvenile kuruma prawns as well as in estuarine ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The significance of resection of para-aortic lymph node metastasis in colorectal cancer is controversial., Objective: To clarify the prognosis of colorectal cancer after para-aortic lymph node metastasis resection., Design: Multicenter retrospective study., Settings: Thirty-six institutions in Japan participated in this study. Database and medical records at each institution were used for data collection., Patients: Patients with resected and pathologically proven para-aortic lymph node metastasis of colorectal cancer between 2010 and 2015 were included., Main Outcome Measures: Overall survival after para-aortic lymph node metastasis resection, recurrence-free survival, and recurrence patterns after R0 resection of para-aortic lymph node metastasis., Results: A total of 133 patients were included in the primary analysis population in this study. The 5-year overall survival rate (95% CI) was 41.0% (32.0-49.8), and the median survival (95% CI) was 4.1 (3.4-4.7) years. Independent prognostic factors for overall survival were the pathological T stage (pT4 vs pT1- 3, adjusted HR: 1.91, p = 0.006), other organ metastasis (present vs absent, adjusted HR: 1.98, p = 0.005), time to metastases (synchronous vs metachronous adjusted HR: 2.02, p = 0.02), and the number of para-aortic lymph node metastasis (3 or more vs less than 3, adjusted HR: 2.13, p = 0.001). The 5-year recurrence-free survival rate (95% CI) was 21.1% (13.5-29.7), with a median (95% CI) of 1.2 (0.9-1.4) years. The primary tumor location (left- vs right-sided colon, adjusted HR: 4.77, p = 0.01; rectum vs right-sided colon, adjusted HR: 5.27, p = 0.006), other organ metastasis (present vs absent, adjusted HR: 1.90, p = 0.03), number of para-aortic lymph node metastases (3 or more vs less than 3, adjusted HR: 2.20, p = 0.001), and hospital volume (less than 10 vs 10 or more, adjusted HR: 2.18, p = 0.02) were identified as independent prognostic factors for recurrence-free survival. Para-aortic lymph node recurrence was the most common at 33.3%., Limitations: Selection bias cannot be ruled out because of the retrospective nature of the study., Conclusions: Less than 3 para-aortic lymph node metastases were a favorable prognostic factor for overall and recurrence-free survival. However, para-aortic lymph node metastases were considered to be a systemic disease, and the significance of resection was limited. See Video Abstract ., Resultado a Largo Plazo Posterior a La Reseccin Quirrgica De Metstasis En Ganglios Linfticos Paraarticos De Cncer Colorrectal Un Estudio Retrospectivo Multicntrico: ANTECEDENTES:La importancia de la resección de metástasis en los ganglios linfáticos paraaórticos (PALNM) en el cáncer colorrectal (CCR) es controvertida.OBJETIVO:Aclarar el pronóstico del CCR después de la resección PALNM.DISEÑO:Estudio retrospectivo multicéntrico.ENTORNO CLINICO:Treinta y seis instituciones en Japón participaron en este estudio.PACIENTES:Pacientes con PALNM de CCR resecado y patológicamente probado entre 2010 y 2015.FUENTES DE DATOS:Base de datos y registros médicos de cada institución.PRINCIPALES MEDIDAS DE RESULTADO:Supervivencia general (SG) después de la resección PALNM, supervivencia libre de recurrencia (SLR) y patrones de recurrencia después de la resección R0 de PALNM.RESULTADOS:Se incluyó un total de 133 pacientes en la población de análisis primario de este estudio. La tasa de SG a 5 años (intervalo de confianza [IC] del 95 %) fue del 41,0 % (32,0, 49,8) y la mediana de supervivencia (IC del 95 %) fue de 4,1 (3,4, 4,7) años. Los factores de pronóstico independientes para la SG fueron el estadio T patológico (pT4 vs. pT1-3, índice de riesgo ajustado [aHR]: 1,91, p = 0,006), metástasis en otros órganos (presente vs. ausente, aHR: 1,98, p = 0,005), tiempo hasta las metástasis (síncronas vs. metacrónicas, aHR: 2,02, p = 0,02) y número de PALNM (≥3 vs. <3, aHR: 2,13, p = 0,001). La tasa de SLR a 5 años (IC del 95%) fue del 21,1% (13,5, 29,7), con una mediana (IC del 95%) de 1,2 (0,9, 1,4) años. La ubicación del tumor primario (colon del lado izquierdo vs. derecho, aHR: 4,77, p = 0,01; recto vs. colon del lado derecho, aHR: 5,27, p = 0,006), metástasis en otros órganos (presente vs. ausente, aHR: 1,90, p = 0,03), el número de PALNM (≥3 vs. <3, aHR: 2,20, p = 0,001) y el volumen hospitalario (<10 vs. ≥10, aHR: 2,18, p = 0,02) se identificaron como independientes factores pronósticos del SLR. La recurrencia de los ganglios linfáticos paraaórticos fue la más común con un 33,3%.LIMITACIONES:No se puede descartar un sesgo de selección debido a la naturaleza retrospectiva del estudio.CONCLUSIONES:Menos de tres PALNM fue un factor pronóstico favorable tanto para la SG como para la SLR. Sin embargo, las PALNM se consideraron una enfermedad sistémica y la importancia de la resección fue limitada. (Traducción- Dr. Francisco M. Abarca-Rendon )., (Copyright © The ASCRS 2024.)

Given Japan's unique social background, it is critical to understand the current risk factors for postpartum hemorrhage (PPH) to effectively manage the condition, especially among specific groups. Therefore, this study aimed to identify the current risk factors for PPH during planned cesarean section (CS) in Japan. This multicenter retrospective cohort study was conducted in two tertiary maternal-fetal medicine units in Fukushima, Japan and included 1,069 women who underwent planned CS between January 1, 2013, and December 31, 2022. Risk factors for PPH (of > 1000 g and > 1500 g) were assessed using multivariate logistic regression analysis, considering variables such as maternal age, parity, assisted reproductive technology (ART) pregnancy, pre-pregnancy body mass index (BMI), uterine myoma, placenta previa, gestational age at delivery, birth weight categories, and hypertensive disorders of pregnancy (HDP). Multivariate linear regression analyses were conducted to predict estimated blood loss during planned CS. ART pregnancy, a pre-pregnancy BMI of 25.0-29.9 kg/m2, and uterine myoma increased PPH risk at various levels. Maternal smoking increased the risk of >1500 g PPH (adjusted odds ratio: 3.09, 95% confidence interval [CI]: 1.16-8.20). Multivariate linear analysis showed that advanced maternal age (B: 83 g; 95% CI: 27-139 g), ART pregnancy (B: 239 g; 95% CI: 121-357 g), pre-pregnancy BMI of 25.0-29.9 kg/m2 (B: 74 g; 95% CI: 22-167 g), uterine myoma (B: 151 g; 95% CI: 47-256 g), smoking (B: 107 g; 95% CI: 13-200 g), and birth weight > 3,500 g (B: 203 g; 95% CI: 67-338 g) were associated with blood loss during planned CS. Considering a patient's clinical characteristic may help predict bleeding in planned CSs and help improve patient safety., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yamaguchi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The outcomes of relapsed or refractory acute myeloid leukemia (AML) remain poor. Although the concomitant use of granulocyte colony-stimulating factor (G-CSF) and anti-chemotherapeutic agents has been investigated to improve the antileukemic effect on AML, its usefulness remains controversial. This study aimed to investigate the effects of G-CSF priming as a remission induction therapy or salvage chemotherapy., Methods: We performed a thorough literature search for studies related to the priming effect of G-CSF using PubMed, Ichushi-Web, and the Cochrane Library. A qualitative analysis of the pooled data was performed, and risk ratios (RRs) with confidence intervals (CIs) were calculated and summarized., Results: Two reviewers independently extracted and accessed the 278 records identified during the initial screening, and 62 full-text articles were assessed for eligibility in second screening. Eleven studies were included in the qualitative analysis and 10 in the meta-analysis. A systematic review revealed that priming with G-CSF did not correlate with an improvement in response rate and overall survival (OS). The result of the meta-analysis revealed the tendency for lower relapse rate in the G-CSF priming groups without inter-study heterogeneity [RR, 0.91 (95% CI 0.82-1.01), p = 0.08; I 2  = 4%, p = 0.35]. In specific populations, including patients with intermediate cytogenetic risk and those receiving high-dose cytarabine, the G-CSF priming regimen prolonged OS., Conclusions: G-CSF priming in combination with intensive remission induction treatment is not universally effective in patients with AML. Further studies are required to identify the patient cohort for which G-CSF priming is recommended., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: The situation of Helicobacter pylori eradication therapy has been changing over time, owing to increases in antimicrobial-resistant strains, lifestyle improvements, and changes in indications for eradication. In Japan, eradication therapy is now available to all H. pylori-positive patients under the medical insurance system, and the potassium-competitive acid blocker vonoprazan has been used for eradication from 2015. Recently, with the aging of society, opportunities to provide eradication to elderly patients are increasing, but the current status and effectiveness of eradication in elderly patients remains unclear. Therefore, we aimed to investigate the trends of H. pylori eradication in a metropolitan area to determine the factors associated with successful H. pylori eradication in elderly patients older than 80 years., Methods: Trends in the eradication rates of patients who received first- or second-line eradication at 20 hospitals in the Tokyo metropolitan area from 2013 to 2023 were investigated., Results: The eradication rates in the per-protocol analysis were 82.3% (95% confidence interval [CI]: 81.2%-83.2%) for the first-line treatment (n = 6481), and 87.9% (86.9%-88.9%) for the second-line treatment (n = 4899). Multivariate analysis showed that independent factors for successful eradication in the first-line treatment were an age of older than 80 years (OR: 0.606; 95% CI: 0.448-0.822), peptic ulcers (vs. atrophic gastritis: 3.817; 3.286-4.433), and vonoprazan (vs. proton pump inhibiters (PPIs), 3.817; 3.286-4.433), and an age of older than 80 years (0.503; 0.362-0.699) and vonoprazan (1.386; 1.153-1.667) in the second-line treatment., Conclusion: After 2015, the eradication rate of both first- and second-line therapies were maintained at a higher level than before 2015, owing to the use of vonoprazan. As the H. pylori eradication rate in patients older than 80 years was low, an effective strategy for these patients needs to be developed in the future., (© 2024 The Author(s). Helicobacter published by John Wiley & Sons Ltd.)

Oral semaglutide has potent anti-hyperglycemic efficacy in phase III trials. However, the complicated dosing instructions hamper to use this drug; therefore, we evaluated the efficacy and safety of oral semaglutide in subjects with type 2 diabetes in a real-world clinical setting. In this multi-center retrospective observational study, we analyzed subjects with type 2 diabetes newly treated with an oral semaglutide for >6 months at four medical centers located in Sapporo, Japan. The changes in glycated hemoglobin, body weight, and other metabolic parameters were evaluated and any adverse event leading to semaglutide discontinuation were recorded from February 2021 to December 2022. This study was registered with the University Hospital Medical Information Network Center (UMIN000050583). Of 543 subjects who met the inclusion criteria, data for 434 subjects (age 55.5 ± 12.6 years; body mass index 29.6 ± 6.0 kg/m 2 ) were analyzed. After a 6 months of observation period, semaglutide 3 mg, 7 mg, or 14 mg was used by 55 (12.7%), 241 (55.5%), and 138 (31.8%) of subjects, respectively. Both glycated hemoglobin and body weight significantly improved: 7.65 ± 1.11% to 6.88 ± 0.91% (p < 0.001) and 80.2 ± 19.2 kg to 77.6 ± 19.2 kg (p < 0.001), respectively. Efficacy was also confirmed in the subgroup switched from other anti-hyperglycemic agents, including dipeptidyl peptidase-4 inhibitors. In total, 154 subjects had symptomatic gastrointestinal symptoms and 39 (7.2%) were discontinued semaglutide due to the adverse events. None of the participants experienced severe hypoglycemic events. Oral semaglutide in subjects with type 2 diabetes improved glycemic control and body weight in a real-world clinical setting.

Background: Granulocyte colony-stimulating factor (G-CSF) reportedly reduces the risk of neutropenia and subsequent infections caused by cancer chemotherapy. Although several guidelines recommend using G-CSF in primary prophylaxis according to the incidence rate of chemotherapy-induced febrile neutropenia (FN), the effectiveness of G-CSF in digestive system tumor chemotherapy remains unclear. To address these clinical questions, we conducted a systematic review as part of revising the Clinical Practice Guidelines for the Use of G-CSF 2022 published by the Japan Society of Clinical Oncology., Methods: This systematic review addressed two main clinical questions (CQ): CQ1: "Is primary prophylaxis with G-CSF effective in chemotherapy?", and CQ2: "Is increasing the intensity of chemotherapy with G-CSF effective?" We reviewed different types of digestive system tumors, including esophageal, gastric, pancreatic, biliary tract, colorectal, and neuroendocrine carcinomas. PubMed, Cochrane Library, and Ichushi-Web databases were searched for information sources. Independent systematic reviewers conducted two rounds of screening and selected relevant records for each CQ. Finally, the working group members synthesized the strength of evidence and recommendations., Results: After two rounds of screening, 5/0/3/0/2/0 records were extracted for CQ1 of esophageal/gastric/pancreatic/biliary tract/colorectal/ and neuroendocrine carcinoma, respectively. Additionally, a total of 2/6/1 records were extracted for CQ2 of esophageal/pancreatic/colorectal cancer, respectively. The strength of evidence and recommendations were evaluated for CQ1 of colorectal cancer; however, we could not synthesize recommendations for other CQs owing to the lack of records., Conclusion: The use of G-CSF for primary prophylaxis in chemotherapy for colorectal cancer is inappropriate., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Most intraoperative adverse events (iAEs) result from surgeons' errors, and bleeding is the majority of iAEs. Recognizing active bleeding timely is important to ensure safe surgery, and artificial intelligence (AI) has great potential for detecting active bleeding and providing real-time surgical support. This study aimed to develop a real-time AI model to detect active intraoperative bleeding., Methods: We extracted 27 surgical videos from a nationwide multi-institutional surgical video database in Japan and divided them at the patient level into three sets: training (n = 21), validation (n = 3), and testing (n = 3). We subsequently extracted the bleeding scenes and labeled distinctively active bleeding and blood pooling frame by frame. We used pre-trained YOLOv7&#95;6w and developed a model to learn both active bleeding and blood pooling. The Average Precision at an Intersection over Union threshold of 0.5 (AP.50) for active bleeding and frames per second (FPS) were quantified. In addition, we conducted two 5-point Likert scales (5 = Excellent, 4 = Good, 3 = Fair, 2 = Poor, and 1 = Fail) questionnaires about sensitivity (the sensitivity score) and number of overdetection areas (the overdetection score) to investigate the surgeons' assessment., Results: We annotated 34,117 images of 254 bleeding events. The AP.50 for active bleeding in the developed model was 0.574 and the FPS was 48.5. Twenty surgeons answered two questionnaires, indicating a sensitivity score of 4.92 and an overdetection score of 4.62 for the model., Conclusions: We developed an AI model to detect active bleeding, achieving real-time processing speed. Our AI model can be used to provide real-time surgical support., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Febrile neutropenia represents a critical oncologic emergency, and its management is pivotal in cancer therapy. In several guidelines, the use of granulocyte colony-stimulating factor (G-CSF) in patients with chemotherapy-induced febrile neutropenia is not routinely recommended except in high-risk cases. The Japan Society of Clinical Oncology has updated its clinical practice guidelines for the use of G-CSF, incorporating a systematic review to address this clinical question., Methods: The systematic review was conducted by performing a comprehensive literature search across PubMed, the Cochrane Library, and Ichushi-Web, focusing on publications from January 1990 to December 2019. Selected studies included randomized controlled trials (RCTs), non-RCTs, and cohort and case-control studies. Evaluated outcomes included overall survival, infection-related mortality, hospitalization duration, quality of life, and pain., Results: The initial search yielded 332 records. Following two rounds of screening, two records were selected for both qualitative and quantitative synthesis including meta-analysis. Regarding infection-related mortality, the event to case ratio was 5:134 (3.73%) in the G-CSF group versus 6:129 (4.65%) in the non-G-CSF group, resulting in a relative risk of 0.83 (95% confidence interval, 0.27-2.58; p = 0.54), which was not statistically significant. Only median values for hospitalization duration were available from the two RCTs, precluding a meta-analysis. For overall survival, quality of life, and pain, no suitable studies were found for analysis, rendering their assessment unfeasible., Conclusion: A weak recommendation is made that G-CSF treatment not be administered to patients with febrile neutropenia during cancer chemotherapy. G-CSF treatment can be considered for patients at high risk., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)