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Background: Floods and torrential rains are natural disasters caused by climate change. Unfortunately, such events are more frequent and are increasingly severe in recent times. The 2018 Japan Floods in western Japan were one of the largest such disasters. This study aimed to evaluate the effect of the 2018 Japan Floods on healthcare costs and service utilization., Methods: This retrospective cohort study included all patients whose receipts accrued between July 2017 and June 2019 in Hiroshima, Okayama, and Ehime prefectures using the National Database of Health Insurance Claims. We used Generalized Estimating Equations (GEEs) to investigate yearly healthcare costs during the pre-and post-disaster periods, quarterly high-cost patients (top 10%), and service utilization (outpatient care, inpatient care, and dispensing pharmacy) during the post-disaster period. After the GEEs, we estimated the average marginal effects as the attributable disaster effect., Results: The total number of participants was 5,534,276. Victims accounted for 0.65% of the total number of participants (n = 36,032). Although there was no significant difference in pre-disaster healthcare costs (p = 0.63), post-disaster costs were $3,382 (95% CI: 3,254-3,510) for victims and $3,027 (95% CI: 3,015-3,038) for non-victims (p < 0.001). The highest risk difference among high-cost patients was 0.8% (95% CI: 0.6-1.1) in the fourth quarter. In contrast, the highest risk difference of service utilization was in the first quarter (outpatient care: 7.0% (95% CI: 6.7-7.4), inpatient care: 1.3% (95% CI: 1.1-1.5), and dispensing pharmacy: 5.9% (95% CI: 5.5-6.4))., Conclusion: Victims of the 2018 Japan Floods had higher medical costs and used more healthcare services than non-victims. In addition, the risk of higher medical costs was highest at the end of the observation period. It is necessary to estimate the increase in healthcare costs according to the disaster scale and plan for appropriate post-disaster healthcare service delivery., (© 2023. The Author(s).)

Background: Brazil has been dramatically hit by the SARS-CoV-2 pandemic and is a world leader in COVID-19 morbidity and mortality. Additionally, the largest country of Latin America has been a continuous source of SARS-CoV-2 variants and shows extraordinary variability of the pandemic strains probably related to the country´s outstanding position as a Latin American economical and transportation hub. Not all regions of the country show sufficient infrastructure for SARS-CoV-2 diagnosis and genotyping which can negatively impact the pandemic response., Methods: Due to this reason and to disburden the diagnostic system of the inner São Paulo State, the Butantan Institute established the Mobile Laboratory (in Portuguese: LabMovel) for SARS-CoV-2 testing which started a trip of the most important "hotspots" of the most populous Brazilian region. The LabMovel initiated in two important cities of the State: Aparecida do Norte (an important religious center) and the Baixada Santista region which incorporates the port of Santos, the busiest in Latin America. The LabMovel was fully equipped with an automatized system for SARS-CoV-2 diagnosis and sequencing/genotyping. It also integrated the laboratory systems for patient records and results divulgation including in the Federal Brazilian Healthcare System., Results: Currently,16,678 samples were tested, among them 1,217 from Aparecida and 4,564 from Baixada Santista. We tracked the delta introductio in the tested regions with its high diversification. The established mobile SARS-CoV-2 laboratory had a major impact on the Public Health System of the included cities including timely delivery of the results to the healthcare agents and the Federal Healthcare system, evaluation of the vaccination status of the positive individuals in the background of exponential vaccination process in Brazil and scientific and technological divulgation of the fieldwork to the most vulnerable populations., Conclusions: The SARS-CoV-2 pandemic has demonstrated worldwide the importance of science to fight against this viral agent and the LabMovel shows that it is possible to integrate researchers, clinicians, healthcare workers and patients to take rapid actions that can in fact mitigate this and other epidemiological situations., (© 2022. The Author(s).)

Introduction: Warm ischemia time (WIT) is a primary concern for robot-assisted laparoscopic partial nephrectomy (RALPN) patients because longer WIT is significantly associated with postoperative deteriorating kidney function. Tumor complexity, determined by the RENAL nephrometry score (RENAL score), can help predict surgical outcomes, but it is unclear what RENAL score and clinical factors affect WIT. This study explored the clinical factors predicting long WIT in experienced surgeon to RALPN., Materials and Methods: In our institute, 174 RALPNs were performed between November 2013 and February 2021, of which 114 were performed by a single surgeon and included in this study. Clinical staging and the total RENAL score were determined based on preoperative CT scans. The cases were divided into three groups based on experience: period 1: 1-38, period 2: 39-76, and period 3: 77-114. The clinical factors associated with longer WIT were analyzed per period., Results: The overall median tumor diameter was 32 mm, and one patient had a positive surgical margin, but there were no cancer-related deaths. In total, there were 18 complications (15.8%). Periods 2 and 3 had larger tumor diameters (p < 0.01) and worse preoperative kidney function (p = 0.029) than period 1. A RENAL L-component score of 3 was associated with longer WIT in period 3 (odds ratio: 3.900; 95% confidence interval: 1.004-15.276; p = 0.044), but the tumor diameter and the total RENAL score were not., Conclusions: A large tumor in the central lesion indicated by the RENAL L-component score was associated with increased WIT in RALPN., (© 2022. The Author(s).)

Background: The frequency and intensity of natural disasters are increasing worldwide, which makes our understanding of disaster-related diseases more important than ever. Natural disasters cause mental stress and infectious diarrhea, but the causal relationship between disasters and a potential consequence of these conditions, irritable bowel syndrome (IBS), is unreported. The 2018 Japan Floods, which took place in July 2018 was one of the largest water disasters in Japan's recorded history. We investigate the change of drug prescriptions for IBS between disaster-suffers and non-sufferers throughout the disaster period to examine the relationship., Methods: This is a retrospective cohort study based on the Japanese National Database of Health Insurance Claims and Specific Health Checkups in flood-stricken areas between July 2017 and June 2019. We included subjects older than 15 years of age who had visited a medical institution or been hospitalized in the hardest-hit areas of the disaster. Ramosetron, polycarbophil calcium, and mepenzolate bromide (IBS drugs) approved solely for the treatment of IBS in Japan were analyzed. The monthly rate of prescriptions for IBS drugs was compared between municipality-certified disaster victims and non-victims using a controlled interrupted time series analysis. For those who were not prescribed IBS drugs before the disaster (non-users), the occurrence of an IBS drug prescription after the disaster was evaluated using a multivariable logistic regression analysis adjusted for gender and age., Results: Of 5,287,888 people enrolled, 32,499 (0.61%) were certified victims. The prescription rate for IBS drugs among victims increased significantly by 128% immediately after the disaster, while it was stable among non-victims. The trend for the post-disaster prescription rate among victims moved upward significantly when compared to non-victims (0.01% per month; 95% confidence interval (CI) 0.004-0.015; P = 0.001). Among non-users, the occurrence of an IBS drug prescription for victims was 0.71% and was significantly higher than non-victims (0.35%, adjusted odds ratio 2.05; 95% CI 1.81-2.32)., Conclusions: The 2018 Japan Floods increased the rate of prescriptions for IBS drugs, suggesting that the disaster caused or worsened IBS among victims., (© 2022. The Author(s).)

Background: Reconstruction surgery-associated stricture frequently occurs in patients with long-gap esophageal atresia (LGEA). While several endoscopic dilatation methods have been applied and would be desirable, endoscopic recanalization is very difficult in cases with complete esophageal closure. Surgical treatment has been performed for a severe stricture, which causes extensive damage to the infant. No reports have described successful endoscopic recanalization for complete closure due to scarring after surgery for LGEA. We herein report the case of successful endoscopic recanalization by single endoscopist in an LGEA patient with complete closure after reconstruction surgery., Case Presentation: A seven-month-old boy with LGEA who received reconstruction surgery and gastrostomy immediately after birth presented to our unit due to vomiting and malnutrition. Contrast radiography and peroral endoscopy detected complete closure of the esophagus at the anastomotic site. After confirming the length of stricture as several millimeters, we punctured the center of the lumen with a 25-G puncture needle under fluoroscopy. An endoscope was then inserted via the gastrostomy and the puncture hole was detected at the center of the lumen. After passing the guidewire, endoscopic balloon dilation was performed three times, and the hole was sufficiently dilatated. Oral ingestion was feasible, and his nutritional condition was improved., Conclusions: To our knowledge, this is the first report to propose a less invasive endoscopic approach to recanalize a site of complete esophageal closure in a LGEA patient after reconstruction surgery by single endoscopist. Our endoscopic procedure using an ultrathin endoscope and puncture needle may be a therapeutic option for the treatment of patients with complete esophageal closure in a LGEA patient after reconstruction surgery., (© 2022. The Author(s).)

Background: Many epidemiological studies have reported the association between exposure to particulate matter and mortality, but long-term prospective studies from Asian populations are sparse. Furthermore, associations at low levels of air pollution are not well clarified. Here, we evaluated associations between long-term exposure to particulate matter <2.5 µg/m 3 (PM 2.5 ) and mortality in a Japanese cohort with a relatively low exposure level., Methods: The Japan Public Health Center-based Prospective Study (JPHC Study) is a prospective cohort study of men and women aged 40-69 years in 1990 who were followed up through 2013 for mortality. In this cohort of 87,385 subjects who did not move residence during follow-up, average PM 2.5 levels from 1998 to 2013 by linkage with 1-km 2 grids of PM 2.5 concentration were assigned to the residential addresses of all participants. To avoid exposure misclassification, we additionally evaluated the association between 5-year (1998-2002) cumulative exposure level and mortality during the follow-up period from 2003 to 2013 in 79,078 subjects. Cox proportional hazards models were used to calculate the association of long-term exposure to PM 2.5 on mortality, with adjustment for several individual confounding factors., Results: Average PM 2.5 was 11.6 µg/m 3 . Average PM 2.5 exposure was not associated with all-cause mortality or cancer and respiratory disease mortality. However, average PM 2.5 was positively associated with mortality from cardiovascular disease (hazard ratio (HR) of 1.23 (95%CI=1.08-1.40) per 1-µg/m 3 increase; in particular, HR in mortality from cerebrovascular disease was 1.34 (95%CI=1.11-1.61) per 1-µg/m 3 increase. Additionally, these results using cumulative 5-year PM 2.5 data were similar to those using average PM 2.5 over 15 years., Conclusions: We found evidence for a positive association between PM 2.5 exposure and mortality from cardiovascular disease in a Japanese population, even in an area with relatively low-level air pollution., (© 2022. The Author(s).)

Background: Most older people with disabilities or illnesses continue to use long-term care (LTC) services for the rest of their lives. However, disasters can cause a discontinuation of LTC services, which usually means tragic outcomes of affected persons. In view of the recent progression of population aging and the increase in natural disasters, this study focuses on the impact of disasters on older people's discontinuation of LTC services, and those more risk of such discontinuation than others. However, current evidence is scarce., Methods: We conducted a retrospective cohort study with 259,081 subjects, 2,762 of whom had been affected by disaster and 256,319 who had not been affected during the 2018 Japan Floods. The sample in the three most disaster-affected prefectures was drawn from the Long-term Care Insurance Comprehensive Database and included older people certified with care-need level. The observation period was two months before the disaster and five months after it. We calculated the hazard ratio (HR) of municipality-certified subjects affected by the disaster versus those who were not. Subgroup analyses were conducted for categories of individual-, facility- and region-associated factors., Results: Affected persons were twice as likely to discontinue LTC services than those who were not affected (adjusted HR, 2.06 95% CI, 1.91-2.23). 34% of affected persons whose facilities were closed discontinued their LTC services at five months after the disaster. A subgroup analysis showed that the risk of discontinuing LTC services for affected persons compared to those who were not affected in the relatively younger subgroup (age < 80: adjusted HR, 2.55; 95% CI, 2.20-2.96 vs. age ≥ 80 : 1.91; 1.75-2.10), and the subgroup requiring a lower level of care (low: 3.16; 2.74-3.66 vs. high: 1.71; 1.50-1.96) were more likely to discontinue than the older and higher care level subgroups., Conclusions: A natural disaster has a significant effect on the older people's discontinuation of LTC services. The discontinuations are supposedly caused by affected persons' death, hospitalization, forced relocation of individuals, or the service provider's incapacity. Accordingly, it is important to recognize the risk of disasters and take measures to avoid discontinuation to protect older persons' quality of life., (© 2022. The Author(s).)

Background: Climate change has increased the frequency and severity of torrential rains and floods around the world. Estimating the costs of these disasters is one of the five global research priorities identified by WHO. The 2018 Japan Floods hit western Japan causing extensive destruction and many deaths, especially among vulnerable elderly. Such affected elderly would need long-term care due to the various health problems caused by the disaster. A Long-Term Care Insurance (LTCI) system provides care services in Japan. The aim of this study was to evaluate the effect of the 2018 Japan Floods on LTCI costs and service utilization., Methods: The participants of this retrospective cohort study were all verified persons utilizing LTCI services in Hiroshima, Okayama and Ehime prefectures. The observation period was from 2 months before to 6 months after the disaster. We used Generalized Estimating Equations (GEEs) to examine the association between disaster status (victims or non-victims) and the monthly total costs of LTCI service (with gamma-distribution/log-link) by residential environment (home or facility). Among home residents, we also examined each service utilization (home-based service, short-stay service and facility service), using the GEEs. After the GEEs, we estimated Average Marginal Effects (AME) over all observation periods by months as the attributable disaster effect., Results: The total number of participants was 279,578. There were 3024 flood victims. The disaster was associated with significantly higher total costs. The AME for home residents at 2 months after was $214 (Standard Error (SE): 12, p < 0.001), which was the highest through the observation period. Among facility residents, the AME immediately after the disaster increased by up to $850 (SE: 29, p < 0.001). The service utilization among home residents showed a different trend for each service. The AME of home-based services decreased by up to - 15.2% (SE:1.3, p < 0.001). The AME for short-stay service increased by up to 8.2% (SE: 0.9, p < 0.001) and the AME for facility service increased by up to 7.4% (SE: 0.7, p < 0.001), respectively., Conclusions: The 2018 Japan Floods caused an increase in LTCI costs and the utilization of short-stay and facility services, and a decrease in utilization of home-based services., (© 2022. The Author(s).)

Background: Inflammatory bowel disease (IBD) is chronic inflammation of the gastrointestinal tract, although its etiology has largely been unclear. Tumor necrosis factor inhibitors (TNF-I) are effective for the treatment. Recently, biosimilars of TNF-I, such as CT-P13, have been developed and are thought to possess equal efficacy and safety to the original TNF-I. Sarcoidosis is also a systemic granulomatous disease of unknown etiology. In steroid-resistant cases of sarcoidosis, TNF-I have been reported effective for achieving resolution. However, the progression of sarcoidosis due to the TNF-I also has been reported. We herein report a case of pulmonary sarcoidosis with a Crohn's disease (CD) patient developed after a long period administration (15 years) of TNF-I., Case Presentations: A 37-year-old woman with CD who had been diagnosed at 22 years old had been treated with the TNF-I (original infliximab; O-IFX and infliximab biosimilar; IFX-BS). Fifteen years after starting the TNF-I, she developed a fever and right chest pain. Chest computed tomography (CT) revealed clustered small nodules in both lungs and multiple enlarged hilar lymph nodes. Infectious diseases including tuberculosis were negative. Bronchoscopic examination was performed and the biopsy specimens were obtained. A pathological examination demonstrated noncaseating granulomatous lesions and no malignant findings. TNF-I were discontinued because of the possibility of TNF-I-related sarcoidosis. After having discontinued for four months, her symptoms and the lesions had disappeared completely. Fortunately, despite the discontinuation of TNF-I, she has maintained remission., Conclusions: To our knowledge, this is the first case in which sarcoidosis developed after switching from O-IFX to IFX-BS. To clarify the characteristics of the cases with development of sarcoidosis during administration of TNF-I, we searched PubMed and identified 106 cases. When developing an unexplained fever, asthenia, uveitis and skin lesions in patients with TNF-I treatment, sarcoidosis should be suspected. Once the diagnosis of sarcoidosis due to TNF-I was made, the discontinuation of TNF-I and administration of steroid therapy should be executed promptly. When re-starting TNF-I, another TNF-I should be used for disease control. Clinicians should be aware of the possibility of sarcoidosis in patients under anti-TNF therapy., (© 2021. The Author(s).)

Background: Japan has established comprehensive education-scholarship programs to supply physicians in rural areas. Their entrants now comprise 16% of all medical students, and graduates must work in rural areas for a designated number of years. These programs are now being adopted outside Japan, but their medium-term outcomes and inter-program differences are unknown., Methods: A nationwide prospective cohort study of newly licensed physicians 2014-2018 (n = 2454) of the four major types of the programs-Jichi Medical University (Jichi); regional quota with scholarship; non-quota with scholarship (scholarship alone); and quota without scholarship (quota alone)-and all Japanese physicians in the same postgraduate year (n = 40,293) was conducted with follow-up workplace information from the Physician Census 2018, Ministry of Health, Labour and Welfare. In addition, annual cross-sectional survey for prefectural governments and medical schools 2014-2019 was conducted to obtain information on the results of National Physician License Examination and retention status for contractual workforce., Results: Passing rate of the National Physician License Examination was highest in Jichi, followed in descending order by quota with scholarship, the other two programs, and all medical graduates. The retention rate for contractual rural service of Jichi graduates 5 years after graduation (n = 683; 98%) was higher than that of quota with scholarship (2868; 90%; P < 0.001) and scholarship alone (2220; 81% < 0.001). Relative risks of working in municipalities with the least population density quintile in Jichi, quota with scholarship, scholarship alone, and quota alone in postgraduate year 5 were 4.0 (95% CI 3.7-4.4; P < 0.001), 3.1 (2.6-3.7; < 0.001), 2.5 (2.1-3.0; < 0.001), and 2.5 (1.9-3.3; < 0.001) as compared with all Japanese physicians. There was no significant difference between each program and all physicians in the proportion of those who specialized in internal medicine or general practice in postgraduate years 3 to 5 CONCLUSIONS: Japan's education policies to produce rural physicians are effective but the degree of effectiveness varies among the programs. Policymakers and medical educators should plan their future rural workforce policies with reference to the effectiveness and variations of these programs., (© 2021. The Author(s).)

Background: Granulocyte and monocyte adsorptive apheresis (GMA) is widely used as a remission induction therapy for active ulcerative colitis (UC) patients. However, there are no available biomarkers for predicting the clinical outcome of GMA. We investigated the utility of Fecal calprotectin (FC) as a biomarker for predicting the clinical outcome during GMA therapy in active UC patients., Methods: In this multicenter prospective observation study, all patients received 10 sessions of GMA, twice a week, for 5 consecutive weeks. FC was measured at entry, one week, two weeks, and at the end of GMA. Colonoscopy was performed at entry and after GMA. The clinical activity was assessed based on the partial Mayo score when FC was measured. Clinical remission (CR) was defined as a partial Mayo score of ≤ 2 and endoscopic remission (ER) was defined as Mayo endoscopic subscore of either 0 or 1. We analyzed the relationships between the clinical outcome (CR and ER) and the change in FC concentration., Result: Twenty-six patients were included in this study. The overall CR and ER rates were 50.0% and 19.2%, respectively. After GMA, the median FC concentration in patients with ER was significantly lower than that in patients without ER (469 mg/kg vs. 3107 mg/kg, p = 0.03). When the cut-off value of FC concentration was set at 1150 mg/kg for assessing ER after GMA, the sensitivity and specificity were 0.8 and 0.81, respectively. The FC concentration had significantly decreased by one week. An ROC analysis demonstrated that the reduction rate of FC (ΔFC) at 1 week was the most accurate predictor of CR at the end of GMA (AUC = 0.852, P = 0.002). When the cut-off value of ΔFC was set at ≤ 40% at 1 week for predicting CR at the end of GMA, the sensitivity and specificity were 76.9% and 84.6%, respectively., Conclusion: We evaluated the utility of FC as a biomarker for assessing ER after GMA and predicting CR in the early phase during GMA in patients with active UC. Our findings will benefit patients with active UC by allowing them to avoid unnecessary invasive procedures and will help establish new strategies for GMA., (© 2021. The Author(s).)

Background: Colorectal cancers develop through several pathways, including the adenoma-carcinoma sequence and colitis-associated carcinogenesis. An altered intestinal microflora has been reported to be associated with the development and progression of colorectal cancer via these pathways. We identified Lactobacillus casei-derived ferrichrome as a mediator of the bacterial anti-tumor effect of colorectal cancer cells through the upregulation of DDIT3. In this study, we investigated the anti-tumor effects of ferrichrome on precancerous conditions and cancer cells associated with sporadic as well as colitis-associated colorectal cancer., Methods: SRB and MTT assays were performed to assess growth inhibition in vitro. Eighteen organoids were prepared from biopsy specimens obtained by colonoscopy. An AOM-DSS carcinogenesis model and xenograft model of colorectal cancer cells were generated for the assessment of the tumor suppressive effect of ferrichrome in vivo., Results: Ferrichrome inhibited the cell growth of colorectal cancer cells in vitro and in in vivo xenograft models. Ferrichrome exerted a strong tumor-suppressive effect that was superior to that of currently available anti-tumor agents, including 5-FU and cisplatin, both in vitro and in vivo. The tumor-suppressive effect of the combination of ferrichrome and 5-FU was superior to that of single treatment with either drug. The tumor suppressive effects of ferrichrome were confirmed through the upregulation of DDIT3 in patient-derived organoids of adenoma and carcinoma. Ferrichrome inhibited the tumor progression in the AOM-DSS model while exhibiting no anti-inflammatory effect in the DSS-colitis model, suggesting that ferrichrome inhibited cancer cells, but not a precancerous condition, via the colitis-associated pathway., Conclusions: Ferrichrome exerts a tumor suppressive effect on precancerous conditions and cancer cells associated with sporadic as well as colitis-associated colorectal cancer. The anti-tumor effect of ferrichrome was mediated by the upregulation of DDIT3, and was superior to that of 5-FU or cisplatin. These results suggest that Lactobacillus brevis-derived ferrichrome may be a candidate anti-tumor drug for the treatment of colorectal neoplasms.

Background: Induced pluripotent stem cells (iPSCs) have enormous potential in developmental biology studies and in cellular therapies. Although extensively studied and characterized in human and murine models, iPSCs from animals other than mice lack reproducible results., Methods: Herein, we describe the generation of robust iPSCs from equine and bovine cells through lentiviral transduction of murine or human transcription factors Oct4, Sox2, Klf4, and c-Myc and from human and murine cells using similar protocols, even when different supplementations were used. The iPSCs were analyzed regarding morphology, gene and protein expression of pluripotency factors, alkaline phosphatase detection, and spontaneous and induced differentiation., Results: Although embryonic-derived stem cells are yet not well characterized in domestic animals, generation of iPS cells from these species is possible through similar protocols used for mouse or human cells, enabling the use of pluripotent cells from large animals for basic or applied purposes. Herein, we also infer that bovine iPS (biPSCs) exhibit similarity to mouse iPSCs (miPSCs), whereas equine iPSs (eiPSCs) to human (hiPSCs)., Conclusions: The generation of reproducible protocols in different animal species will provide an informative tool for producing in vitro autologous pluripotent cells from domestic animals. These cells will create new opportunities in animal breeding through transgenic technology and will support a new era of translational medicine with large animal models.

Background: Geographical maldistribution of physicians, and their subsequent shortage in rural areas, has been a serious problem in Japan and in other countries. Family Medicine, a new board-certified specialty started 10 years ago in Japan by Japan Primary Care Association (JPCA), may be a solution to this problem., Methods: We obtained the workplace information of 527 (78.4%) of the 672 JPCA-certified family physicians from an online database. From the national census data, we also obtained the workplace information of board-certified general internists, surgeons, obstetricians/gynaecologists and paediatricians and of all physicians as the same-generation comparison group (ages 30 to 49). Chi-squared test and residual analysis were conducted to compare the distribution between family physicians and other specialists., Results: Five hundred nineteen JPCA-certified family physicians and 137,587 same-generation physicians were analysed. The distribution of family physicians was skewed to municipalities with a lower population density, which shows a sharp contrast to the urban-biased distribution of other specialists. The proportion of family physicians in non-metropolitan municipalities was significantly higher than that expected based on the distribution of all same-generation physicians (p < 0.001)., Conclusions: Family physicians distributed in favour of rural areas much more than any other specialists in Japan. The better balance of family physician distribution reported from countries with a strong primary care orientation seems to hold even in a country where primary care orientation is weak, physician distribution is not regulated, and patients have free access to healthcare. Family physicians comprise only 0.2% of all Japanese physicians. However, if their population grows, they can potentially rectify the imbalance of physician distribution. Government support is mandatory to promote family medicine in Japan.

Background: Pancreatic cancer is associated with an extremely poor prognosis, so new biomarkers that can detect the initial stages are urgently needed. The significance of serum microRNA (miR) levels in pancreatic neoplasm such as pancreatic cancer and intraductal papillary mucinous neoplasm (IPMN) diagnosis remains unclear. We herein evaluated the usefulness of miRs enclosed in serum exosomes (ExmiRs) as diagnostic markers., Methods: The ExmiRs from patients with pancreatic cancer (n = 32) or IPMN (n = 29), and patients without neoplasms (controls; n = 22) were enriched using ExoQuick-TC™. The expression of ExmiRs was evaluated using a next-generation sequencing analysis, and the selected three miRs through this analysis were confirmed by a quantitative real-time polymerase chain reaction., Results: The expression of ExmiR-191, ExmiR-21 and ExmiR-451a was significantly up-regulated in patients with pancreatic cancer and IPMN compared to the controls (p < 0.05). A receiver operating characteristic curve analysis showed that the area under the curve and the diagnostic accuracy of ExmiRs were 5-20% superior to those of three serum bulky circulating miRs (e.g.; ExmiR-21: AUC 0.826, accuracy 80.8%. Circulating miR-21: AUC 0.653, accuracy 62.3%). In addition, high ExmiR-451a was associated with mural nodules in IPMN (p = 0.010), and high ExmiR-21 was identified as a candidate prognostic factor for the overall survival (p = 0.011, HR 4.071, median OS of high-ExmiR-21: 344 days, median OS of low-ExmiR-21: 846 days) and chemo-resistant markers (p = 0.022)., Conclusions: The level of three ExmiRs can thus serve as early diagnostic and progression markers of pancreatic cancer and IPMN, and considered more useful markers than the circulating miRs (limited to these three miRs).

Objective: Helicobacter pylori (H. pylori) eradication rarely develops into antibiotic-associated hemorrhagic colitis (AAHC), in which the etiology of colitis remains unclear. We herein report a rare case of AAHC caused by second-line therapy for H. pylori eradication., Results: A 65-year-old female was administered second-line therapy for H. pylori composed of 1500 mg of amoxicillin, 500 mg of metronidazole and 40 mg of vonoprazan for 7 days because of first-line therapy failure. A day after completing second-line therapy, she complained of abdominal pain and hematochezia. Colonoscopy revealed a hemorrhage and edematous mucosa with no transparent vascular pattern in the transverse colon. A bacterial culture detected Klebsiella oxytoca (K. oxytoca), but no other pathogenic bacteria. A drug-induced lymphocyte stimulation test (DLST) showed positive reactions for both amoxicillin and metronidazole. According to these findings, the patient was diagnosed with AAHC. Bowel rest for 6 days relieved her abdominal pain and hematochezia., Conclusions: The present case developed AAHC caused by second-line therapy for H. pylori eradication. The pathogenesis is considered to be associated with microbial substitution as well as a delayed-type allergy to antibiotics, suggesting that AAHC is a potential adverse event of second-line therapy for H. pylori eradication.

Background: In Japan, the number of obstetrics facilities has steadily decreased and the selection and concentration of obstetrics facilities is progressing rapidly. Obstetrics services should be concentrated in fewer hospitals to improve quality of care and reduce the workload of obstetricians. However, the impact of this intensification of services on access to obstetrics hospitals is not known. We undertook a simulation to examine how the intensification of obstetrics services would affect access to hospitals based on a variety of scenarios, and the implications for health policy., Methods: The female population aged between 15 and 49 living within a 30-min drive of an obstetrics hospital was calculated using a Geographic Information System for three possible intensification scenarios: Scenario 1 retained facilities with a higher volume of deliveries without considering the geographic boundaries of Medical Service Areas (MSAs, zones of healthcare administration and management); Scenario 2 prioritized retaining at least one hospital in each MSA and then retained higher delivery volume institutions, while Scenario 3 retained facilities to maximize population coverage using location-allocation modeling. We also assessed the impact of concentrating services in academic hospitals and specialist perinatal medical centers (PMCs) alone., Results: In 2011, 95.0% of women aged 15-49 years lived within a 30-min drive of one of 1075 obstetrics hospitals. This would fall to 82.7% if obstetrics services were intensified into academic hospitals and general and regional PMCs. If 55.0% of institutions provided obstetrics services, the coverage would be 87.6% in Scenario 1, whereas intensification based on access would achieve over 90.5% coverage in Scenario 2 and 93.9% in Scenario 3., Conclusions: Intensification of obstetrics facilities impairs access, but a greater caseload and better staffing have the potential advantages of better clinical outcomes and reduced costs. It is essential to consult residents of hospital catchment areas when reorganizing clinical services; a simulation is a useful means of informing these important discussions.

Background: Epidemiological studies have shown adverse effects of short-term exposure to air pollution on respiratory disease outcomes; however, few studies examined this association on an hourly time scale. We evaluated the associations between hourly changes in air pollution and the risk of respiratory disease in the elderly, using the time of the emergency call as the disease onset for each case., Methods: We used a time-stratified case-crossover design. Study participants were 6,925 residents of the city of Okayama, Japan, aged 65 or above who were taken to hospital emergency rooms between January 2006 and December 2010 for onset of respiratory disease. We calculated city-representative hourly average concentrations of air pollutants from several monitoring stations. By using conditional logistic regression models, we estimated odds ratios per interquartile-range increase in each pollutant by exposure period prior to emergency call, adjusting for hourly ambient temperature, hourly relative humidity, and weekly numbers of reported influenza cases aged ≥60., Results: Suspended particulate matter (SPM) exposure 24 to <72 hours prior to the onset and ozone exposure 48 to <96 hours prior to the onset were associated with the increased risk of respiratory disease. For example, following one interquartile-range increase, odds ratios were 1.05 (95% confidence interval: 1.01, 1.09) for SPM exposure 24 to <48 hours prior to the onset and 1.13 (95% confidence interval: 1.04, 1.23) for ozone exposure 72 to <96 hours prior to the onset. Sulfur dioxide (SO2) exposure 0 to <24 hours prior to onset was associated with the increased risk of pneumonia and influenza: odds ratio was 1.07 per one interquartile-range increase (95% confidence interval: 1.00, 1.14). Elevated risk for pneumonia and influenza of SO2 was observed at shorter lags (i.e., 8-18 hours) than the elevated risks for respiratory disease of SPM or ozone. Overall, the effect estimates for chronic obstructive pulmonary disease and allied conditions were equivocal., Conclusions: This study provides further evidence that hourly changes in air pollution exposure increase the risks of respiratory disease, and that SO2 may be related with more immediate onset of the disease than other pollutants.

Background: Exposure to air pollution has been demonstrated to increase the risk of preterm birth and low birth weight (LBW). Although evidence has accumulated on characteristics associated with increased risk of air pollution-related health effects, most studies have been conducted in the adult population and evidence on reproductive outcomes is limited. We examined whether socio-economic position (SEP) and parental characteristics (parental behavior and co-morbidity) modified the relationship between air pollution and adverse birth outcomes., Methods: Data were extracted from a perinatal hospital database based in Shizuoka, Japan. We restricted the analysis to mothers who delivered live-born single births from January 1997 to December 2010 (n = 16,615). Each birth was assigned proximity to major roads. Multivariate adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated for the outcomes of preterm birth and term LBW. We stratified subjects by individual/area-level SEP and parental characteristics. We then measured interactions on the additive scale between the respective factors and exposure., Results: Lower SEP at both individual and area levels was associated with the increased occurrence of adverse birth outcomes. Living within 200 m from a major road increased the risk of preterm birth by 1.5 times (95% CI: 1.3-1.9) and LBW by 1.2 times (95% CI: 0.9-1.6). Mothers with lower individual SEP defined by household occupation experienced higher ORs for term LBW (OR = 3.1, 95% CI: 1.2-8.2) compared with those with higher individual SEP. In contrast, mothers who lived in the highest area-level SEP region (i.e., affluent areas) showed slightly higher point estimates compared with those who lived in middle or poor areas. In addition, maternal diabetic and hypertensive status modified the association between proximity and preterm birth, while maternal smoking status modified the association between proximity and term LBW., Conclusions: The present study demonstrated that air pollution is an independent risk factor for adverse birth outcomes. Mothers with lower individual SEP and mothers living in higher SEP region may be susceptible to the adverse effect of air pollution. Maternal diabetic, hypertensive, and smoking status may also increase susceptibility to this air pollution-related health effect.

Background: The proportions of preterm birth (PTB, ie., delivered before 37 gestational weeks) and low birth weight (LBW, ie., birth weight less than 2500 g at delivery) have been rising in developed countries. We sought to examine the factors contributing to the rise in Japan, with particular focus on the effects of obstetric interventions., Methods: We used a database maintained by one large regional hospital in Shizuoka, Japan. We restricted the analysis to mothers who delivered live singleton births from 1997 to 2010 (n = 19,221). We assessed the temporal trends in PTB and LBW, then divided the study period into four intervals and compared the proportions of PTB and LBW. We also compared the newborns' outcomes between the intervals., Results: PTB, in particular medically indicated PTB, increased considerably. The increase was largely explained by changes in caesarean sections. The neonatal outcomes did not worsen, and instead the Apgar scores and proportions requiring neonatal intensive care unit (NICU) admission improved. In particular, the risks of NICU admission in the interval from 2007 to 2010 were decreased among all births [odds ratio (OR): 0.84; 95% confidence interval (CI): 0.75, 0.95] and medically indicated births (OR: 0.44; 95% CI: 0.29, 0.68) compared with the interval from 1997 to 2000., Conclusions: Despite the increases in PTB as well as LBW, the present study suggests benefits of obstetric interventions. Rather than simple categorization of PTB or LBW, indicators such as perinatal mortality or other outcomes may be more appropriate for evaluation of perinatal health in developed countries.

Background: Frequent and long-term commuting is a requirement for dialysis patients. Accessibility thus affects their quality of lives. In this paper, a new model for accessibility measurement is proposed in which both geographic distance and facility capacity are taken into account. Simulation of closure of rural facilities and that of capacity transfer between urban and rural facilities are conducted to evaluate the impacts of these phenomena on equity of accessibility among dialysis patients., Methods: Post code information as of August 2011 of all the 7,374 patients certified by municipalities of Hiroshima prefecture as having first or third grade renal disability were collected. Information on post code and the maximum number of outpatients (capacity) of all the 98 dialysis facilities were also collected. Using geographic information systems, patient commuting times were calculated in two models: one that takes into account road distance (distance model), and the other that takes into account both the road distance and facility capacity (capacity-distance model). Simulations of closures of rural and urban facilities were then conducted., Results: The median commuting time among rural patients was more than twice as long as that among urban patients (15 versus 7 minutes, p<0.001). In the capacity-distance model 36.1% of patients commuted to the facilities which were different from the facilities in the distance model, creating a substantial gap of commuting time between the two models. In the simulation, when five rural public facilitiess were closed, Gini coefficient of commuting times among the patients increased by 16%, indicating a substantial worsening of equity, and the number of patients with commuting times longer than 90 minutes increased by 72 times. In contrast, closure of four urban public facilities with similar capacities did not affect these values., Conclusions: Closures of dialysis facilities in rural areas have a substantially larger impact on equity of commuting times among dialysis patients than closures of urban facilities. The accessibility simulations using the capacity-distance model will provide an analytic framework upon which rational resource distribution policies might be planned.

Background: Some patients under close colonoscopic surveillance still develop colorectal cancer, thus suggesting the overlook of colorectal adenoma by endoscopists. AFI detects colorectal adenoma as a clear magenta, therefore the efficacy of AFI is expected to improve the detection ability of colorectal adenoma. The aim of this study is to determine the efficacy of AFI in detecting colorectal adenoma., Methods: This study enrolled 88 patients who underwent colonoscopy at Asahikawa Medical University and Kushiro Medical Association Hospital. A randomly selected colonoscopist first observed the sigmoid colon and rectum with conventional high resolution endosopy (HRE). Then the colonoscopist changed the mode to AFI and handed to the scope to another colonoscopist who knew no information about the HRE. Then the second colonoscopist observed the sigmoid colon and rectum. Each colonoscopist separately recorded the findings. The detection rate, miss rate and procedural time were assessed in prospective manner., Results: The detection rate of flat and depressed adenoma, but not elevated adenoma, by AFI is significantly higher than that by HRE. In less-experienced endoscopists, AFI dramatically increased the detection rate (30.3%) and reduced miss rate (0%) of colorectal adenoma in comparison to those of HRE (7.7%, 50.0%), but not for experienced endoscopists. The procedural time of HRE was significantly shorter than that of AFI., Conclusions: AFI increased the detection rate and reduced the miss rate of flat and depressed adenomas. These advantages of AFI were limited to less-experienced endoscopists because experienced endoscopists exhibited a substantially high detection rate for colorectal adenoma with HRE.

Background: Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF) are Chronic Myeloproliferative Neoplasms (MPN) characterized by clonal myeloproliferation/myeloaccumulation without cell maturation impairment. The JAK2 V617F mutation and PRV1 gene overexpression may contribute to MPN physiopathology. We hypothesized that deregulation of the apoptotic machinery may also play a role in the pathogenesis of ET and PMF. In this study we evaluated the apoptosis-related gene and protein expression of BCL2 family members in bone marrow CD34+ hematopoietic stem cells (HSC) and peripheral blood leukocytes from ET and PMF patients. We also tested whether the gene expression results were correlated with JAK2 V617F allele burden percentage, PRV1 overexpression, and clinical and laboratory parameters., Results: By real time PCR assay, we observed that A1, MCL1, BIK and BID, as well as A1, BCLW and BAK gene expression were increased in ET and PMF CD34+ cells respectively, while pro-apoptotic BAX and anti-apoptotic BCL2 mRNA levels were found to be lower in ET and PMF CD34+ cells respectively, in relation to controls. In patients' leukocytes, we detected an upregulation of anti-apoptotic genes A1, BCL2, BCL-XL and BCLW. In contrast, pro-apoptotic BID and BIMEL expression were downregulated in ET leukocytes. Increased BCL-XL protein expression in PMF leukocytes and decreased BID protein expression in ET leukocytes were observed by Western Blot. In ET leukocytes, we found a correlation between JAK2 V617F allele burden and BAX, BIK and BAD gene expression and between A1, BAX and BIK and PRV1 gene expression. A negative correlation between PRV1 gene expression and platelet count was observed, as well as a positive correlation between PRV1 gene expression and splenomegaly., Conclusions: Our results suggest the participation of intrinsic apoptosis pathway in the MPN physiopathology. In addition, PRV1 and JAK2 V617F allele burden were linked to deregulation of the apoptotic machinery.