Difference between Keratinized- and Non-Keratinized-Originating Epithelium in the Process of Immune Escape of Oral Squamous Cell Carcinoma.

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are significantly changing treatment strategies for human malignant diseases, including oral cancer. Cancer cells usually escape from the immune system and acquire proliferative capacity and invasive/metastatic potential. We have focused on the two immune checkpoints, PD-1/PD-L1 and CD47/SIRPα, in the tumor microenvironment of oral squamous cell carcinoma (OSCC), performed a retrospective analysis of the expression of seven immune-related factors (PD-L1, PD-1, CD4, CD8, CD47, CD56 and CD11c), and examined their correlation with clinicopathological status. As a result, there were no significant findings relating to seven immune-related factors and several clinicopathological statuses. However, the immune checkpoint-related factors (PD-1, PD-L1, CD47) were highly expressed in non-keratinized epithelium-originated tumors when compared to those in keratinized epithelium-originated tumors. It is of interest that immunoediting via immune checkpoint-related factors was facilitated in non-keratinized sites. Several researchers reported that the keratinization of oral mucosal epithelia affected the immune response, but our present finding is the first study to show a difference in tumor immunity in the originating epithelium of OSCC, keratinized or non-keratinized. Tumor immunity, an immune escape status of OSCC, might be different in the originating epithelium, keratinized or non-keratinized.

Cost of illness for colorectal cancer in Japan - a time trend and future projections (1996-2035) based on governmental statistics.

BACKGROUND: In Japan, the crude mortality rate of colorectal cancer is the second highest among men and highest among women by site. We aimed to calculate the social burden of colorectal cancer using the cost of illness (COI) method and identify the main factors that drove changes in the COI. METHODS: From 1996 to 2020, the COI was estimated by summing direct, morbidity, and mortality costs. In addition, the COI by 2035 was projected by fitting approximate curves obtained from historical data to health-related indicators by sex and age. Future projections of the number of patients by the stage of disease were also made to explore the factors that changed the COI. RESULTS: The number of deaths and incidence from colorectal cancer was expected to continue increasing due to population aging. However, the COI was projected to rise from 850.3 billion yen in 1996 to 1.451 trillion yen in 2020, and peaked at 1.478 trillion yen in 2023 before it declined. CONCLUSION: Although the increased number of deaths associated with population aging increased COI, it was expected that the COI would decrease around 2023 due to a decrease in the human capital value of the deceased. In addition, the mortality rate was expected to decrease in the future due to an increase in the percentage of early detection of colorectal cancer via widespread screening and advances in medical technology.

Involvement of methodological experts and the quality of clinical practice guidelines: a critical appraisal of clinical practice guidelines and a questionnaire survey of the development groups in Japan.

OBJECTIVE: To evaluate whether the involvement of methodological experts improves the quality of clinical practice guidelines (CPGs) after adjusting for other factors. SETTING: The quality of Japanese CPGs published in 2011-2019 was assessed using the Appraisal of Guidelines, Research, and Evaluation (AGREE) II instrument. A questionnaire survey targeting CPG development groups was conducted through postal mail. PARTICIPANTS: 405 CPGs were retrieved from a Japanese CPG clearinghouse. Questionnaires were distributed to the 405 CPG development groups. Of the 178 respondents, 22 were excluded because of missing values. Finally, 156 participants representing their CPG development groups were included in the analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: CPG quality was assessed using the AGREE II tool. The characteristics of CPGs, including publication year, development organisation, versions, number of members in the development group and involvement of methodological experts, were corrected from the description in the CPGs and the questionnaire survey. We performed multiple logistic regressions using the quality of CPGs as the dependent variable and the involvement of experts as the independent variable, adjusting for other possible factors. RESULTS: A total of 156 CPGs were included. Expert involvement was significantly associated with the AGREE II instrument scores in domains 1 (ß=0.207), 2 (ß=0.370), 3 (ß=0.413), 4 (ß=0.289), 5 (ß=0.375), 6 (ß=0.240) and overall (ß=0.344). CONCLUSION: This study revealed that the involvement of methodological experts in the CPG development process improves the quality of CPGs. The results suggest the importance of establishing a training and certification programme for experts and constructing expert referral systems that meet CPG developers' needs to improve the quality of CPGs.

Development and usability of a hospital standardized ADL ratio (HSAR) for elderly patients with cerebral infarction: a retrospective observational study using administrative claim data from 2012 to 2019 in Japan.

BACKGROUND: Maintenance of activities of daily living (ADL) during acute hospitalization is an important treatment goal, especially for elderly inpatients with diseases that often leave disabilities, such as cerebral infarction. However, studies assessing risk-adjusted ADL changes are limited. In this study, we developed and calculated a hospital standardized ADL ratio (HSAR) using Japanese administrative claims data to measure the quality of hospitalization care for patients with cerebral infarction. METHODS: This study was designed as a retrospective observational study using the Japanese administrative claim data from 2012 to 2019. The data of all hospital admissions with a primary diagnosis of cerebral infarction (ICD-10, I63) were used. The HSAR was defined as the ratio of the observed number of ADL maintenance patients to the expected number of ADL maintenance patients multiplied by 100, and ratio of ADL maintenance patients was risk-adjusted using multivariable logistic regression analyses. The c-statistic was used to evaluate the predictive accuracy of the logistic models. Changes in HSARs in each consecutive period were assessed using Spearman's correlation coefficient. RESULTS: A total of 36,401 patients from 22 hospitals were included in this study. All variables used in the analyses were associated with ADL maintenance, and evaluations using the HSAR model showed predictive ability with c-statistics (area under the curve, 0.89; 95% confidence interval, 0.88-0.89). CONCLUSIONS: The findings indicated a need to support hospitals with a low HSAR because hospitals with high/low HSAR were likely to produce the same results in the subsequent periods. HSAR can be used as a new quality indicator of in-hospital care and may contribute to the assessment and improvement of the quality of care.

Difference in prioritization of patient safety interventions between experts and patient safety managers in Japan.

Although a variety of patient safety interventions have been implemented, prioritizing them in a limited resource environment is important. The intervention priorities of patient safety managers may differ from those of patient safety experts. This study aimed to clarify the difference in prioritization of interventions between experts and safety managers to better identify interventions that should be promoted in Japan. We performed a secondary data analysis of two surveys: the Delphi survey for Japanese experts and a nationwide questionnaire survey for safety managers in hospitals. Regarding the 32 interventions constituting 14 organizational-level and 18 clinical-level interventions examined in the previous studies, we assessed three correlations to examine the difference in prioritization between experts and safety managers: correlations between experts and safety managers in the three perspectives (contribution, dissemination, and priority), those between priorities of experts and safety managers at the clinical and organizational level, and those among the three perspectives in experts and safety managers. Contribution (r = 0.768) and dissemination (r = 0.689) of patient safety interventions evaluated by experts and safety managers were positively correlated, but priorities were not. Interventions with priorities that differed between experts and safety managers were identified. In experts, there was no significant correlation between contribution and priority or between dissemination and priority. For safety managers, contributions (r = 0.812) and dissemination (r = 0.691) were positively correlated with priority. Our results suggest that patient safety managers evaluated future priority based on past contributions and current dissemination, whereas experts evaluated future priority based on other factors, such as expected impacts in the future, as mentioned in the previous study. In health policymaking, promotion of patient safety interventions that were given high priority by experts, but low priority by safety managers, should be considered with possible incentives.

Primary syphilis with a tongue ulcer mimicking tongue cancer: a case report.

The main symptom in primary syphilis is a small, painless, sore or ulcer called a chancre on the penis, vagina, or around the anus, although chancres can sometimes appear in the mouth or on the lips, fingers, or buttocks. We present the case of a man in his early 60 s with a chief complaint of a painful tongue ulcer. An ulcerated, indurated, and hemorrhagic lesion (23 × 14 mm) was found on the ventral tongue surface, near the oral floor. Palpation identified several swollen, mobile, elastic cervical lymph nodes, with no tenderness. We initially diagnosed tongue cancer; however, during a subsequent detailed examination for a malignant tumor, including biopsy and obtaining additional history, his disease was finally identified as primary syphilis with multiple swollen cervical lymph nodes. Oral amoxicillin and probenecid were started, and after 14 days, there was partial reduction in the size of the submandibular lymph nodes and the ulcer on the left tongue margin. The number of patients with syphilis in Japan increased by eight times from 2012 to 2018. We suggest that dentists consider primary syphilis as a differential diagnosis for oral refractory ulcer with induration and obtain a detailed patient history.

Social burden of three major diseases in Japan: A time trend and future projections using the comprehensive cost of illness method.

BACKGROUND: Three major diseases in Japan, cancer, heart disease, and cerebrovascular disease (CVD) are the leading causes of death in Japan. This study aimed to clarify the social burden of these diseases, including long-term care (LTC), and to predict future trends. METHODS: The comprehensive cost of illness (C-COI), a modification of the cost of illness (COI), was used to estimate the social burden of the three major diseases in Japan. The C-COI can macroscopically estimate both direct and indirect costs, including the LTC. A new method for future projections of the C-COI was developed according to the method for future projections of the COI. All data sources were government statistics. RESULTS: The C-COI of cancer, heart diseases, and CVD in 2017 amounted to 11.0 trillion JPY, 5.3 trillion JPY, and 6.5 trillion JPY, respectively. The projected future C-COI in 2029 was 10.3 trillion JPY, 5.3 trillion JPY, and 4.4 trillion JPY, respectively. In 2029, the LTC costs accounted for 4.4%, 12.8%, and 44.1% of the total C-COI, respectively. Informal care costs are projected to be approximately 1.7 times higher, assuming that all family caregivers will be replaced by professional caregivers in 2029. CONCLUSION: Indirect costs for all three diseases were projected to decrease owing to aging of the patient. In contrast to the other two diseases, the LTC cost of CVD accounted for a large proportion of the burden. The burden of CVD is expected to decrease in the future, but informal care by older family caregivers is suggested to reach its limits. In the future, the focus of resource allocation should shift from medical care to LTC, especially support for family caregivers. A method of future projections for the social burden based on the C-COI was considered effective for identifying issues for healthcare policy in the context of the times.

Cost of illness in a super-aged society-comparison of breast, lung, and prostate cancer in Japan.

BACKGROUND: Aging increases the disease burden because of an increase in disease prevalence and mortality among older individuals. This could influence the perception of the social burden of different diseases and treatment prioritization within national healthcare services. Cancer is a disease with a high disease burden in Japan; however, the age-specific frequency and age-specific mortality rates differ according to site. In this study, we evaluated the relationship between the aging of the Japanese society and the disease burden by comparing the features of three cancers with different age-specific frequency rates in Japan. Furthermore, we made projections for the future to determine how the social burden of these cancers will change. METHODS: We calculated the social burden of breast, lung, and prostate cancers by adding the direct, morbidity, and mortality costs. Estimates were made using the cost of illness (COI) method. For future projections, approximate curves were fitted for mortality rate, number of hospital admissions per population, number of outpatient visits per population, and average length of hospital stay according to sex and age. RESULTS: The COI of breast, lung, and prostate cancers in 2017 was 903.7, 1,547.6, and 390.8 billion yen, respectively. Although the COI of breast and prostate cancers was projected to increase, that of lung cancer COI was expected to decrease. In 2017, the average age at death was 68.8, 76.8, and 80.7 years for breast, lung, and prostate cancers, respectively. CONCLUSIONS: Patients with breast cancer die earlier than those with other types of cancer. The COI of breast cancer ("young cancer") was projected to increase slightly because of an increase in mortality costs, whereas that of prostate cancer ("aged cancer") was projected to increase because of an increase in direct costs. The COI of lung cancer ("aging cancer") was expected to decrease in 2020, despite the increase in deaths, as the impact of the decrease in human capital value outweighed that of the increase in deaths. Our findings will help prioritize future policymaking, such as cancer control research grants.

The mutational spectrum in whole exon of p53 in oral squamous cell carcinoma and its clinical implications.

Mutations in p53 are common in human oral squamous cell carcinoma (OSCC). However, in previous analyses, only detection of mutant p53 protein using immunohistochemistry or mutations in some exons have been examined. Full length mutant p53 protein in many cases shows a loss of tumor suppressor function, but in some cases possibly shows a gain of oncogenic function. In this study, we investigate relationships of outcomes with the mutational spectrum of p53 (missense and truncation mutations) in whole exon in OSCC. Specimens from biopsy or surgery (67 cases) were evaluated using next-generation sequencing for p53, and other oncogenic driver genes. The data were compared with overall survival (OS) and disease-free survival (DFS) using univariate and multivariate analyses. p53 mutations were detected in 54 patients (80.6%), 33 missense mutations and 24 truncation mutations. p53 mutations were common in the DNA-binding domain (43/52) and many were missense mutations (31/43). Mutations in other regions were mostly p53 truncation mutations. We detected some mutations in 6 oncogenic driver genes on 67 OSCC, 25 in NOTCH1, 14 in CDKN2A, 5 in PIK3CA, 3 in FBXW7, 3 in HRAS, and 1 in BRAF. However, there was no associations of the p53 mutational spectrum with mutations of oncogenic driver genes in OSCC. A comparison of cases with p53 mutations (missense or truncation) with wild-type p53 cases showed a significant difference in lymph node metastasis. DFS was significantly poorer in cases with p53 truncation mutations. Cases with p53 truncation mutations increased malignancy. In contrast, significant differences were not found between cases with p53 missense mutations and other mutations. The p53 missense mutation cases might include cases with mostly similar function to that of the wild-type, cases with loss of function, and cases with various degrees of gain of oncogenic function.

Cross-cultural adaptation and validation of the Chinese version of the revised surveys on patient safety culture™ (SOPS®) hospital survey 2.0.

BACKGROUND: Surveys on Patient Safety Culture™ (SOPS®) Hospital Survey (HSOPS 1.0), developed by the U.S. Agency for Healthcare Research and Quality in 2004, has been widely adopted in the United States and internationally. An updated version, the SOPS Hospital Survey 2.0 (HSOPS 2.0), released in 2019, has not yet been applied in China. The aim of the present study was to translate HSOPS 2.0 into Chinese version with cross-cultural adaptations and test its psychometric properties. METHODS: A convenience sample was used. Hospital nurses (N = 1013) and a sub-set (n = 200) was invited for the re-test. A three-stage study was conducted. Firstly, the HSOPS 2.0 was translated by a panel. Secondly, the content validity was tested using the two-round Delphi method and cognitive interview. Next, the construct validity was tested by the confirmatory factor analysis and further demonstrated by the convergent validity, discriminant validity, and correlations with the outcome of patient safety. Thirdly, the reliability was tested by internal consistency reliability and re-test reliability. RESULTS: The "float or PRN" and "manager" words were deleted as considered unfitted for the Chinese health care system. The content validity index provided evidence of strong content validity (I-CVI = 0.84 ~ 1.00, S-CVI = 0.98). Confirmatory factor analysis revealed a good model fit (χ2/df = 4.05, RMSEA = 0.06, CFI = 0.94) and acceptable factor loadings (0.41 ~ 0.97). Convergent validity, and discriminant validity supported the factorial structure of the Chinese version of HSOPS 2.0. Further evidence for the construct validity was derived from correlations with the outcome of patient safety (r = 0.10 ~ 0.41). A good internal consistency (Cronbach's α = 0.68 ~ 0.93, McDonald's omega = 0.84 ~ 0.96) and test-retest reliability (ICC = 0.78 ~ 0.95) showed acceptable reliability. Additionally, Chinese nurses reported markedly lower scores for three dimensions, including "Response to Error", "Communication Openness", and "Reporting Patient Safety Events", when comparing the findings of this study with those from U.S. research utilizing the HSOPS 2.0. CONCLUSION: The Chinese version of HSOPS 2.0 demonstrated good validity and reliability in a Chinese sample of hospital nurses, which suggests that it can be used to measure nurse-perceived patient safety culture in future research and practice. Psychometric properties of the Chinese version of HSOPS 2.0 among other Chinese healthcare professionals remain to be confirmed.

Evaluating the Hospital Standardized Home-Transition Ratios for Cerebral Infarction in Japan: A Retrospective Observational Study from 2016 through 2020.

Discharge to home is considered appropriate as a treatment goal for diseases that often leave disabilities such as cerebral infarction. Previous studies showed differences in risk-adjusted in-hospital mortality and readmission rates; however, studies assessing the rate of hospital-to-home transition are limited. We developed and calculated the hospital standardized home-transition ratio (HSHR) using Japanese administrative claims data from 2016-2020 to measure the quality of in-hospital care for cerebral infarction. Overall, 24,529 inpatients at 35 hospitals were included. All variables used in the analyses were associated with transition to another hospital or facility for inpatients, and evaluation of the HSHR model showed good predictive ability with c-statistics (area under curve, 0.73 standard deviation; 95% confidence interval, 0.72-0.73). All HSHRs of each consecutive year were significantly correlated. HSHRs for cerebral infarction can be calculated using Japanese administrative claims data. It was found that there is a need for support for low HSHR hospitals because hospitals with high/low HSHR were likely to produce the same results in the following year. HSHRs can be used as a new quality indicator of in-hospital care and may contribute to assessing and improving the quality of care.

Hospital-level characteristics of the standardised mortality ratio for ischemic heart disease: a retrospective observational study using Japanese administrative claim data from 2012 to 2019.

Background: Ischemic heart disease (IHD) is one of the leading causes of mortality worldwide and imposes a heavy burden on patients. Previous studies have indicated that the optimal care for IHD during hospitalisation may reduce the risk of in-hospital mortality. The standardised mortality ratio (SMR) is an indicator for assessing the risk-adjusted in-hospital mortality ratio based on case-mix. This indicator can crucially identify hospitals that can be changed to improve patient safety and the quality of care. This study aimed to determine the hospital-level characteristics of the SMR for IHD in Japan. Methods: This study was designed as a retrospective observational study using the Japanese administrative claim data from 2012 to 2019. The data of all hospital admissions with a primary diagnosis of IHD (ICD-10, I20-I25) were used. Patients with complete variables data were included in this study. Hospitals with less than 200 IHD inpatients in each 2-year period were excluded. The SMR was defined as the ratio of the observed number of in-hospital deaths to the expected number of in-hospital deaths multiplied by 100.The observed number of in-hospital deaths was the sum of the actual number of in-hospital deaths at that hospital, and the expected number of in-hospital deaths was the sum of the probabilities of in-hospital deaths. Ratios of in-hospital mortality was risk-adjusted using multivariable logistic regression analyses. The c-statistic and Hosmer-Lemeshow test were used to evaluate the predictive accuracy of the logistic models. Changes in SMRs in each consecutive period were assessed using Spearman's correlation coefficient. Results: A total of 64,831 were admitted patients with IHD in 27 hospitals as complete submission data. The SMRs showed wide variation among hospitals, ranging from 35.4 to 197.6, and analysis models indicated good predictive ability with a c-statistic of 0.93 (95% CI [0.92-0.94]) and Hosmer-Lemeshow test of 0.30. The results of chi-square tests and t-tests for all variables to assess the association with in-hospital mortality were P < 0.001. In the analysis of trends in each consecutive period, the SMRs showed positive correlations. Conclusions: This study denoted that the SMRs for IHD could be calculated using Japanese administrative claim data. The SMR for IHD might contribute to the development of more appropriate benchmarking systems for hospitals to improve quality of care.

Trends in the development process of clinical practice guidelines: a questionnaire survey for the guideline development groups in Japan.

BACKGROUND: Clinical practice guidelines (CPGs) are representative methods for promoting healthcare standardization and improving its quality. Previous studies on the CPG (published by 2006) development process in Japan reported that the involvement of experts and patients, efficient evidence collection and appraisal, and paucity of evidence on Japanese patients should be improved for the efficient CPG development. This study aimed to clarify the trends of CPG development process in Japan, focusing on the involvement of experts and patients, efficient evidence collection and appraisal, and paucity of Japanese evidence. METHODS: A cross-sectional questionnaire survey was conducted for CPG development groups to collect information on the development activities of the CPGs published from 2012 to 2019. These CPGs were identified from the Japanese guideline clearinghouse. The questionnaire included the questions on composing the group, securing funding sources, collecting and appraising the research evidence, and the difficulties in the CPG development process. The questionnaires were distributed to the chairpersons of the CPG development groups through postal mail from November 2020 to January 2021. Combining the data from the current survey with those of previous studies reporting the development process of CPGs published by 2011, we analyzed the trend in the CPG development process. RESULTS: Of the total 265 CPGs included in the analysis, 164 (response rate: 41.4%) were from the current survey and 101 (response rate: 44.5%) were from previous studies. Among these, 40 (15.1%) were published by 2005, 47 (17.7%) in 2006-2010, 77 (29.1%) in 2011-2015, and 101 (38.1%) in 2016-2019. The proportion of CPGs involving methodologists did not increase through the publication periods. The proportion of CPGs involving patients almost doubled from the first period (15.9%) to the fourth period (32.4%). The yield rates of the articles did not change through the publication periods. The difficulty in "Coping with the paucity of Japanese evidence" has been improving consistently (69.2% in the first period to 37.4% in the fourth period). CONCLUSIONS: Our results suggest the need for methodological improvement in the efficient collection and appraisal of evidence and in the system assigning experts to the CPG development groups.

Surveillance for Patients with Oral Squamous Cell Carcinoma after Complete Surgical Resection as Primary Treatment: A Single-Center Retrospective Cohort Study.

BACKGROUND: The surveillance methods oral squamous cell carcinoma (OSCC) patients may be chosen by considering the risk for recurrence, and it is important to establish appropriate methods during the period in which latent/dormant cancer cells become more apparent. To investigate the appropriate surveillance of patients with OSCC based on the individual risk for recurrence and/or metastasis, we performed a retrospective cohort study after the complete surgical resection of OSCC as the primary treatment. METHODS: The study was performed in 324 patients with OSCC who had been primarily treated with surgery from 2007 to 2020 at our hospital. We investigated the period, timing, and methods (visual examination, palpation and imaging using FDG-PET/CT or CECT) for surveillance in each case that comprised postsurgical treatment. RESULTS: Regarding the time to occurrence of postsurgical events, we found that half of cases of local recurrence, cervical lymph node metastasis, and distant metastasis occurred within 200 days, and 75% of all of these events occurred within 400 days. However, the mean time for second primary cancer was 1589 days. The postsurgical events were detected earlier by imaging examinations than they were by visual examination and palpation. CONCLUSIONS: For the surveillance of patients with OSCC after primary surgery, it is desirable to perform FDG-PET/CT within 3-6 months and at 1 year after surgery and to consider CECT as an option in between FDG-PET/CT, while continuing history and physical examinations for about 5 years based on individual risk assessment.

Identification of Binding Proteins for TSC22D1 Family Proteins Using Mass Spectrometry.

TSC-22 (TGF-ß stimulated clone-22) has been reported to induce differentiation, growth inhibition, and apoptosis in various cells. TSC-22 is a member of a family in which many proteins are produced from four different family genes. TSC-22 (corresponding to TSC22D1-2) is composed of 144 amino acids translated from a short variant mRNA of the TSC22D1 gene. In this study, we attempted to determine the intracellular localizations of the TSC22D1 family proteins (TSC22D1-1, TSC-22 (TSC22D1-2), and TSC22(86) (TSC22D1-3)) and identify the binding proteins for TSC22D1 family proteins by mass spectrometry. We determined that TSC22D1-1 was mostly localized in the nucleus, TSC-22 (TSC22D1-2) was localized in the cytoplasm, mainly in the mitochondria and translocated from the cytoplasm to the nucleus after DNA damage, and TSC22(86) (TSC22D1-3) was localized in both the cytoplasm and nucleus. We identified multiple candidates of binding proteins for TSC22D1 family proteins in in vitro pull-down assays and in vivo binding assays. Histone H1 bound to TSC-22 (TSC22D1-2) or TSC22(86) (TSC22D1-3) in the nucleus. Guanine nucleotide-binding protein-like 3 (GNL3), which is also known as nucleostemin, bound to TSC-22 (TSC22D1-2) in the nucleus. Further investigation of the interaction of the candidate binding proteins with TSC22D1 family proteins would clarify the biological roles of TSC22D1 family proteins in several cell systems.

Morphometric and histomorphometric evaluations of high-purity macro/microporous beta-tricalcium phosphate in maxillary sinus floor elevation: preliminary results on a retrospective, multi-center, observational study.

BACKGROUND: The present study examined the effectiveness of high-purity macro/microporous beta-tricalcium phosphate (HPMM ß-TCP) as a bone grafting material for maxillary sinus floor elevation by morphometric, histopathological, and histomorphometric evaluations. METHODS: Ten unilateral maxillary sinus floor elevation procedures using 100% HPMM ß-TCP were performed in 10 patients. Morphometric evaluation was carried out by computed tomography (CT) imaging immediately after augmentation and prior to dental implant placement 7 months later. Histopathological and histomorphometric evaluations were carried out by bone biopsy retrieval at the time of dental implant placement 7 months after sinus floor elevation. RESULTS: All 10 sinus floor elevations were successful. Morphometric evaluation by CT showed that the vertical height and volume gained by sinus floor elevation decreased 7 months after surgery. Histopathological evaluation of bone biopsy retrieval specimens showed no signs of inflammation at the newly formed bone area and the native alveolar bone area. New bone formation was observed at the cranial side from the native alveolar bone. The newly formed bone had a trabecular structure and was in intimate contact with the HPMM ß-TCP material. Histomorphometric evaluation of bone biopsy retrieval specimens showed an average new bone volume of 33.97% ± 2.79% and an average residual HPMM ß-TCP volume of 15.81% ± 4.52%. CONCLUSIONS: In this study, HPMM ß-TCP showed osteoconductive properties for vertical augmentation of the atrophied maxilla by means of a maxillary sinus floor elevation procedure allowing subsequent dental implant placement after a 7-month healing period.

Patient safety management systems and activities related to promoting voluntary in-hospital reporting and mandatory national-level reporting for patient safety issues: A cross-sectional study.

Both voluntary in-hospital reporting and mandatory national-level reporting systems for patient safety issues need to work well to develop a patient safety learning system that is effective in preventing the recurrence of adverse events. Some of the hospital systems and activities may increase voluntary in-hospital reporting and mandatory national-level reporting. This study aimed to identify the hospital systems and activities that increase voluntary in-hospital reporting and mandatory national-level reporting for patient safety issues. An anonymous mail survey of hospitals in Japan was conducted in 2017. The hospitals were selected by stratified random sampling according to number of beds. The survey examined the annual number of reported events in the voluntary in-hospital reporting system for patient safety and experience of reporting unexpected patient deaths possibly due to medical interventions to the mandatory national-level reporting system in the last 2 years. The relationship of the answer to the questions with the patient safety management systems and activities at each hospital was analyzed. The response rate was 18.8% (603/3,215). The number of in-hospital reports per bed was positively related to identifying events by referring complaints or questions of patients or family members, using root cause analysis for analyzing reported events, and developing manuals or case studies based on reported events, and negatively related to the unification and standardization of medical devices and equipment. The experience with mandatory national-level reporting of serious adverse events was positively related to identifying problematic cases by a person in charge of patient safety management from the in-hospital reporting system of complications and accidental symptoms. Enhanced feedback for reporters may promote voluntary in-hospital reporting of minor cases with low litigation risks. Developing an in-hospital mechanism that examines all serious complications and accidental symptoms may promote mandatory national-level reporting of serious adverse events with high litigation risks.

Characteristics and Trends of the Hospital Standardized Readmission Ratios for Pneumonia: A Retrospective Observational Study Using Japanese Administrative Claims Data from 2010 to 2018.

Previous studies indicated that optimal care for pneumonia during hospitalization might reduce the risk of in-hospital mortality and subsequent readmission. This study was a retrospective observational study using Japanese administrative claims data from April 2010 to March 2019. We analyzed data from 167,120 inpatients with pneumonia ≥15 years old in the benchmarking project managed by All Japan Hospital Association. Hospital-level risk-adjusted ratios of 30-day readmission for pneumonia were calculated using multivariable logistic regression analyses. The Spearman's correlation coefficient was used to assess the correlation in each consecutive period. In the analysis using complete 9-year data including 54,756 inpatients, the hospital standardized readmission ratios (HSRRs) showed wide variation among hospitals and improvement trend (r = -0.18, p = 0.03). In the analyses of trends in each consecutive period, the HSRRS were positively correlated between '2010-2012' and '2013-2015' (r = 0.255, p = 0.010), and '2013-2015' and '2016-2018' (r = 0.603, p < 0.001). This study denoted the HSRRs for pneumonia could be calculated using Japanese administrative claims data. The HSRRs significantly varied among hospitals with comparable case-mix, and could relatively evaluate the quality of preventing readmission including long-term trends. The HSRRs can be used as yet another measure to help improve quality of care over time if other indicators are examined in parallel.

Oral squamous cell carcinoma may originate from bone marrow-derived stem cells.

Molecules that demonstrate a clear association with the aggressiveness of oral squamous cell carcinoma (OSCC) have not yet been identified. The current study hypothesized that tumor cells in OSCC have three different origins: Epithelial stem cells, oral tissue stem cells from the salivary gland and bone marrow (BM) stem cells. It was also hypothesized that carcinomas derived from less-differentiated stem cells have a greater malignancy. In the present study, sex chromosome analysis by fluorescence in situ hybridization and/or microdissection PCR was performed in patients with OSCC that developed after hematopoietic stem cell transplantation (HSCT) from the opposite sex. OSCC from 3 male patients among the 6 total transplanted patients were considered to originate from donor-derived BM cells. A total of 2/3 patients had distant metastasis, resulting in a poor prognosis. In a female patient with oral potentially malignant disorder who underwent HSCT, there were 10.7% Y-containing cells in epithelial cells, suggesting that some epithelial cells were from the donor. Subsequently, gene expression patterns in patients with possible BM stem cell-derived OSCC were compared with those in patients with normally developed OSCC by microarray analysis. A total of 3 patients with BM stem cell-derived OSCC exhibited a specific pattern of gene expression. Following cluster analysis by the probes identified on BM stem cell-derived OSCC, 2 patients with normally developed OSCC were included in the cluster of BM stem cell-derived OSCC. If the genes that could discriminate the origin of OSCC were identified, OSCCs were classified into the three aforementioned categories. If diagnosis can be performed based on the origin of the cancer cells, a more specific therapeutic strategy may be implemented to improve prognosis. This would be a paradigm shift in diagnostic and therapeutic strategies for OSCC.

Effectiveness of cetuximab as preemptive postsurgical therapy for oral squamous cell carcinoma patients with major risk: a single-center retrospective cohort study.

A retrospective cohort study was performed to investigate the effectiveness of preemptive postsurgical therapy with cetuximab for patients with a major risk of recurrence or metastasis after clinical complete resection of primary oral squamous cell carcinoma (OSCC). The study period was from 2007 to 2019 for patients treated at the Department of Oral and Maxillofacial Surgery, Dokkyo Medical University School of Medicine. OSCC patients with major risk (n = 88) in the follow-up period were divided into groups with no postsurgical treatment (NP group), with standard postsurgical treatment (SP group), and with postsurgical treatment including cetuximab (CP group), and prognosis were compared among those groups. The 5-year overall survival rate was significantly higher in patients who received postsurgical treatment with cetuximab (CP) compared to that in the other two groups ((CP vs. NP, p = 0.028; CP vs. SP, p = 0.042). Furthermore, we performed multivariate analysis to evaluate the effects of the main components of the treatment. Among CDDP, radiotherapy, and cetuximab, only cetuximab significantly contributed to improved survival by univariate analysis (crude HR:0.228, 95%CI:0.05-0.968, p = 0.045). cetuximab also showed the same tendency in multivariate analysis, although p value did not reach significant level (Adjusted HR: 0.233, 95%CI: 0.053-1.028, p = 0.054). The results suggest that the postsurgical treatment with cetuximab as a preemptive postsurgical therapy after complete surgical resection of a visible tumor is considerably effective for OSCC patients with major risk, in other words, invisible dormant metastasis.