Association between hospital case volume and maternal adverse events in patients with placental abruption: An analysis using a Japanese national inpatient database.

OBJECTIVE: To clarify the relationship between the prognosis of patients with placental abruption (PA) and the healthcare delivery system using data from a large national inpatient database in Japan. METHODS: Using the Diagnosis Procedure Combination database, we conducted a retrospective cohort study with the data of patients in almost 1000 hospitals with the primary diagnosis of PA who were hospitalized from April 2014 to March 2021. We divided the hospitals into four groups based on the number of deliveries per month. We performed multilevel logistic regression analysis to analyze the relationship between hospital case volume and maternal end-organ injury (MEOI). RESULTS: Altogether, 8222 patients were included for analysis; among whom, 3575 (44%) were transferred by ambulance. MEOI was noted in 977 patients (12%) with no obvious difference by hospital case volume. Ambulance transfer, age, gestational weeks at admission, delivery on the first day of hospitalization, and history of eclampsia were significantly associated with a higher incidence of MEOI, but the hospital case volume was not. CONCLUSION: Using a Japanese administrative database, our study shows that hospital case volume was not significantly associated with the severity of maternal illness among patients with PA.

Analyzing attempt and success factors for amputated digit replantation in Japan using the diagnosis procedure combination database.

The number of amputated finger replantation has declined in the USA and Germany in recent years; however, there have been no reports on recent trends in Japan. We examined the current practices, attempts, and success factors of digit replantation in Japan. We hypothesized that the rates of digit replantation and success rates were consistently standardized in Japan. The diagnosis procedure combination database was used to analyze 14004 cases from April 2014 to March 2020, excluding multiple-digit amputations, thus focusing on 13484 patients. We evaluated replantation success rates and identified factors influencing replantation decisions using multiple logistic regression analysis. The key findings included a higher frequency of replantation in thumb cases and surgeries during overtime hours, on Sundays, and in educational institutions. Success rates were notably higher for thumb replantations and patients under 20 years of age. Patients over 65 years of age treated with urokinase showed higher failure rates, unrelated to regional or hospital case volumes. The number of amputated digit replantation surgeries in Japan was high during overtime hours, on Sundays, and in educational institutions. Region, hospital type, and hospital case volume were not associated with a low success rate across Japan.

Diffusible fraction of niche BMP ligand safeguards stem-cell differentiation.

Drosophila male germline stem cells (GSCs) reside at the tip of the testis and surround a cluster of niche cells. Decapentaplegic (Dpp) is one of the well-established ligands and has a major role in maintaining stem cells located in close proximity. However, the existence and the role of the diffusible fraction of Dpp outside of the niche have been unclear. Here, using genetically-encoded nanobodies called Morphotraps, we physically block Dpp diffusion without interfering with niche-stem cell signaling and find that a diffusible fraction of Dpp is required to ensure differentiation of GSC daughter cells, opposite of its role in maintenance of GSC in the niche. Our work provides an example in which a soluble niche ligand induces opposed cellular responses in stem cells versus in differentiating descendants to ensure spatial control of the niche. This may be a common mechanism to regulate tissue homeostasis.

Epidemiologic evaluation of pulmonary paragonimiasis in Japan using a Japanese nationwide administrative database.

BACKGROUND: Paragonimiasis is a parasitic disease primarily contracted through consumption of undercooked freshwater crustaceans or wild boar meat. Large-scale nationwide epidemiological data on paragonimiasis are lacking. In this study, we aimed to investigate the nationwide epidemiology of hospitalized patients with paragonimiasis in Japan using a comprehensive nationwide Japanese administrative database. METHODS: We evaluated the Japanese Diagnosis Procedure Combination (DPC) data of patients diagnosed with pulmonary paragonimiasis between April 1, 2012 and March 30, 2020. The patients' address and information, including age, sex, treatment (medication: praziquantel; surgery: open thoracotomy or intracranial mass extirpation), Japan coma scale, comorbidities, and length of hospital stay, were extracted. RESULTS: Of the 49.6 million hospitalized patients, data were extracted on 73 patients with paragonimiasis, of whom 36 were male and 37 were female. The mean age was 49.7 years and the mean length of stay was 12.5 days. The most frequent comorbidity was pleural effusion (31.5 %), followed by pneumothorax (13.7 %). The sites of ectopic paragonimiasis in organs other than the lung included the liver (5.5 %), skin (4.1 %), and brain (2.7 %). Geographically, most patients were from the Kyushu region (54.8 %), followed by the Kanto region (22.0 %). Fukuoka Prefecture had the highest number of patients (22.0 %) by prefecture. During the study period, an average of 9.1 patients/year were hospitalized with lung paragonimiasis in Japan. CONCLUSION: Paragonimiasis has not completely disappeared in Japan; thus, physicians should be aware of paragonimiasis in the Kyushu region, especially in the Fukuoka Prefecture.

Dally is not essential for Dpp spreading or internalization but for Dpp stability by antagonizing Tkv-mediated Dpp internalization.

Dpp/BMP acts as a morphogen to provide positional information in the Drosophila wing disc. Key cell-surface molecules to control Dpp morphogen gradient formation and signaling are heparan sulfate proteoglycans (HSPGs). In the wing disc, two HSPGs, the glypicans Division abnormally delayed (Dally) and Dally-like (Dlp) have been suggested to act redundantly to control these processes through direct interaction of their heparan sulfate (HS) chains with Dpp. Based on this assumption, a number of models on how glypicans control Dpp gradient formation and signaling have been proposed, including facilitating or hindering Dpp spreading, stabilizing Dpp on the cell surface, or recycling Dpp. However, how distinct HSPGs act remains largely unknown. Here, we generate genome-engineering platforms for the two glypicans and find that only Dally is critical for Dpp gradient formation and signaling through interaction of its core protein with Dpp. We also find that this interaction is not sufficient and that the HS chains of Dally are essential for these functions largely without interacting with Dpp. We provide evidence that the HS chains of Dally are not essential for spreading or recycling of Dpp but for stabilizing Dpp on the cell surface by antagonizing receptor-mediated Dpp internalization. These results provide new insights into how distinct HSPGs control morphogen gradient formation and signaling during development.

Short-term effectiveness and safety of rituximab versus cyclophosphamide for life-threatening ANCA-associated vasculitis: a propensity score analysis of the real-world nationwide database.

OBJECTIVES: Life-threatening antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with rapidly progressive glomerulonephritis (RPGN) and/or alveolar haemorrhage (AH) has a poor prognosis. Rituximab (RTX) is as effective as cyclophosphamide (CY) in remission induction therapy; however, the effectiveness and safety of RTX have not been established in life-threatening AAV. This study aimed to investigate the short-term effectiveness and safety of RTX in life-threatening AAV with RPGN and/or AH. METHODS: Between April 2018 and March 2020, cases treated with systemic glucocorticoids and RTX or intravenous CY (IVCY) was extracted from a Japanese nationwide inpatient database. Effectiveness was evaluated by in-hospital mortality and severe renal dysfunction requiring haemodialysis (HD) at discharge. Safety was evaluated by the in-hospital incidence of infections. The propensity score (PS) for RTX was estimated. Multivariable Cox and logistic regression with adjustment for PS were conducted to estimate the association of RTX with outcomes. RESULTS: From 16 001 612 hospitalised records, 687 life-threatening AAV cases were extracted. No significant difference in in-hospital mortality (adjusted HR 1.06; 95% CI 0.62 to 1.80) was found between the groups. Although the RTX group had a lower risk of fungal infections (adjusted OR (aOR) 0.45; 95% CI 0.23 to 0.84) and pneumocystis pneumonia (aOR 0.58; 95% CI 0.32 to 1.00), they might have an increased risk of severe renal dysfunction requiring HD at discharge (aOR 2.58; 95% CI 1.02 to 6.91). CONCLUSIONS: In life-threatening AAV, RTX has similar short-term effectiveness on mortality to IVCY. Although RTX might have a lower risk of fungal infections and pneumocystis pneumonia, the short-term renal prognosis might be inferior to IVCY.

Impact of fee-revision policy for gastrostomy on its implementation among older adults with dementia in Japan.

OBJECTIVES: This study aimed to evaluate the impact of the policy to reduce the reimbursement fee for percutaneous endoscopic gastrostomy (PEG) on the number of PEG procedures performed among older adults with dementia. STUDY DESIGN: Interrupted time series (ITS). METHODS: We used the monthly aggregated data of the number of PEG procedures in older adults with dementia (both broad and narrow definitions), between 2012 and 2018, from the claims data in Fukuoka Prefecture, Japan. A single ITS design was used to estimate changes in the outcome following each intervention (i.e., first, second, and third interventions performed in 2014, 2015, and 2016, respectively). A controlled ITS design was applied to estimate the effects after the sequence of interventions (pre-intervention: 2012-2014; post-intervention: 2016-2018). The control group comprised patients with malignant head and neck tumors who underwent PEG procedures outside the scope of this policy restriction. RESULTS: The number of PEG procedures decreased significantly only in the month wherein the third intervention was introduced (broad definition: IRR = 0.11, CI = 0.03-0.49; narrow definition: IRR = 0.15, CI = 0.03-0.75). No significant difference was observed between the treatment and control groups during the post-intervention phase. CONCLUSIONS: The impact of fee-revision policy for PEG on the decrease in PEG procedures among older adults with dementia is remarkably minimal. It is difficult to reduce unnecessary PEG procedures by relying on this financial incentive alone. Policy decision-makers should consider methods to prevent inappropriate use of artificial nutrition for older adults at their end-of-life stage by reforming the health delivery system.

The Relationship Between Preoperative Frailty Risk as Assessed by the Hospital Frailty Risk Score and the Outcome at Discharge in Coronary Artery Bypass Grafting (CABG) Patients: A Retrospective Observational Study Using the Diagnosis Procedure Combination Database.

The relationship between the Hospital Frailty Risk Score (HFRS)-based frailty risk and outcomes after coronary artery bypass grafting (CABG) is yet unclear. The objective of this study was to investigate the relationship between preoperative frailty risk as assessed by the HFRS and postoperative outcomes in patients undergoing CABG. This observational study used the diagnosis procedure combination (DPC) system in Japan (2014-2017). In total, 35,015 adults aged ≥ 65 years and diagnosed with angina pectoris and acute myocardial infarction who had undergone CABG were enrolled. We investigated the association between the HFRS-based frailty risk and the home discharge rate, as well as the prevalence of complications. Multilevel logistic regression analysis revealed that having an HFRS ≥ 5 was a determinant of lower home discharge rate (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.49-0.74, P <0.01), aspiration pneumonia (OR 2.25, 95%CI 1.27-3.96, P <0.01) and disuse syndrome (OR 1.90, 95%CI 1.23-2.94, P <0.01). Preoperative stratification of frailty risk using HFRS may help in predicting postoperative progress and in planning postoperative rehabilitation.

Physical Rehabilitation and Post-Stroke Pneumonia: A Retrospective Observational Study Using the Japanese Diagnosis Procedure Combination Database.

In this study, the relationship between the duration of physical rehabilitation and occurrence of pneumonia after ischemic stroke was examined. We included 426,508 patients aged ≥75 years with acute ischemic stroke. A multilevel logistic regression analysis nested at the hospital level was conducted to examine the association between the duration of physical rehabilitation and occurrence of pneumonia. The duration of physical rehabilitation refers to the hours of physical rehabilitation performed daily until the 7th day of hospitalization. In the multivariable analysis, the intensity of rehabilitation for durations of 20-39 min/day (adjusted odds ratio [aOR]: 0.78, 95% Confidence Interval [CI]: 0.75-0.81, p < 0.001), 40-59 min/day (aOR: 0.68, 95% CI: 0.66-0.71, p < 0.001), 60-79 min/day (aOR:0.56, 95% CI: 0.53-0.58, p < 0.001), and ≥80 min/day (aOR: 0.46, 95% CI: 0.44-0.48, p < 0.001) were significantly associated with a reduced incidence of pneumonia. In addition, the trend identified for duration of rehabilitation was significant (p < 0.001). The results of this study suggest the usefulness of high-duration physical rehabilitation for preventing pneumonia in older patients with ischemic stroke.

Predictors of hospital mortality and multidrug-resistant pathogens in hospitalized pneumonia patients residing in the community.

Background and objective: The 2019 ATS/ADSA guidelines for adult community-acquired pneumonia (CAP) eliminated healthcare-associated pneumonia (HCAP) and considered it to be a form of CAP. This concept, however, was based on studies with relatively small sample sizes. Methods: We investigated the risk factors of 30-day mortality, and methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa infections in patients with pneumonia coming from the community using the Diagnosis Procedure Combination database, a nationwide discharge database of acute care hospitals. Furthermore, we compared these factors between CAP and HCAP. Results: A total of 272,337 patients aged ≥20 years with pneumonia were grouped into 145,082 CAP patients and 127,255 HCAP patients. The 30-day mortality rate (8.9 % vs.3.3 %), MRSA infection (2.4 % vs. 1.4 %), and Pseudomonas aeruginosa infection (1.6 % vs. 1.0 %) were significantly higher in HCAP than in CAP patients. Multivariable logistic regression analysis showed that 12 of 13 identified predictors of mortality (i.e., high age, male, underweight, non-ambulatory status, bedsore, dehydration, respiratory failure, consciousness disturbance, hypotension, admitted in critical care, comorbidity of heart failure, and chronic obstructive pulmonary disease) were identical in CAP and HCAP patients. Similarly, five of six distinct risk factors for MRSA infection, and three of three for Pseudomonas aeruginosa infection were identical between the patients. Conclusion: The risk factors for mortality and MRSA or Pseudomonas aeruginosa infection were almost identical in patients with CAP and HCAP. The assessment of individual risk factors for mortality and MRSA or Pseudomonas aeruginosa infection in CAP and abandoning categorization as HCAP can improve and simplify empiric therapy.

Short-term outcomes of pancreatoduodenectomy in older individuals over a 9-year period using real-world data: A multilevel analysis based on a nationwide administrative database in Japan.

BACKGROUND: We aimed to evaluate the short-term outcomes of pancreatoduodenectomy (PD) in older individuals. METHODS: Data from the Japanese Diagnosis Procedure Combination database on 62 275 patients who underwent PD from 1 April 2012 to 31 March 2020 were analyzed. Patients were divided into five age groups: <70, 70-74, 75-79, 80-84, and ≥85 years. The associations between postoperative outcomes and age were investigated using multilevel analysis. The mean differences in length of hospital stay and cost were also compared. RESULTS: The rate of PD in older individuals increased annually. Compared with the youngest age group (< 70 years), the incidence rate ratios for in-hospital mortality were 1.52 (95% confidence interval [CI]: 1.30-1.76), 2.07 (1.82-2.37), 2.29 (1.94-2.71), and 2.92 (2.20-3.87) in the 70-74, 75-79, 80-84, and ≥ 85-year-old age groups, respectively (all p < .001). Postoperative complications, length of postoperative hospital stay, and cost increased significantly with increasing age. CONCLUSIONS: These real-world data emphasize the higher levels of morbidity, mortality, and cost in older patients. Careful attention should be paid when considering the indication for PD in older individuals.

Atrial fibrillation and mortality after ischemic stroke: An observational study using an insurance claim database.

OBJECTIVES: In this study, we aimed to examine the association between atrial fibrillation and mortality after ischemic stroke and evaluate the use of anticoagulation therapy for atrial fibrillation before stroke onset in patients who experienced stroke. METHODS: In this retrospective observational study, we used a combined database of medical and long-term care insurance claims data from one prefecture in Japan. The data of 25,352 patients aged ≥ 65 years who were hospitalized in acute care hospitals with a diagnosis of ischemic stroke between April 2012 and March 2015 were extracted. Cox proportional hazard modeling, with adjustment for age, sex, comorbidities, and long-term care dependency level (based on the activities of daily living), was performed to evaluate the relationship between mortality and atrial fibrillation. RESULTS: The prevalence of atrial fibrillation was 21.8% in the study population. A significant association was noted between mortality and atrial fibrillation (adjusted hazard ratio: 1.28, 95% confidence interval: 1.16-1.41, p < 0.001). Anticoagulant drugs were used in 32.2% of the patients with atrial fibrillation. CONCLUSIONS: These results indicate that atrial fibrillation is associated with mortality after stroke; however, the use of anticoagulation therapy for atrial fibrillation is unsatisfactory. Efforts to improve the use of atrial fibrillation therapy are required in Japan.

The Current Status of Suicide and Medical Care System in Japan: An Analysis of 81,407 Patients Using the Diagnosis Procedure Combination Database.

Japan has a high suicide mortality rate compared to other developed countries. To reduce suicide mortality in Japan, it is important to systematically analyze factors related to death of patients with suicide attempt. This study aimed to analyze the characteristics of patients with suicide attempt, and the factors related to their death using the Diagnosis Procedure Combination (DPC) data- a nationally representative inpatient database. We collected 81,407 cases of suicide attempt from 2016 to 2018 from DPC data and performed a multilevel logistic analysis of factors associated with death discharges. The analysis results showed that patients who received psychiatric liaison care had a lower mortality rate, but only 0.6% of surviving patients received psychiatric liaison care after admission. The odds ratio (OR) of death was high for hanging (28.86; p < 0.001) and jumping (16.28; p < 0.001), compared to wrist cutting. Patients without a psychiatric diagnosis were more likely to choose means such as hanging (14.1%) than those with a psychiatric disorder. The weekend cases had a higher OR of death than weekday (Wednesday as reference) cases (Friday 1.14, p = 0.011; Saturday 1.60, p < 0.001; Sunday 1.67, p < 0.001). Based on these findings, we suggest that improving the availability and quality of psychiatric care in acute care hospitals and primary care settings, as well as enhancing the emergency department system on weekends, could help reduce the mortality of suicide attempts.

Association of Preoperative Rehabilitation With Postoperative Length of Hospital Stay for Elderly Lung Cancer Patients.

This study aimed to evaluate the effect of preoperative rehabilitation on postoperative hospital stay in elderly lung cancer patients following lung resection. This was a retrospective observational study using the Japanese Diagnosis Procedure Combination database. Data of patients diagnosed between April 2016 and March 2020 were collected. Patients were identified using the International Statistical Classification of Disease and Related Health Problems Version 10-10 codes, C34.0-C34.3 and C34.8. Multilevel linear regression analysis was performed to evaluate the effect of preoperative rehabilitation on the length of hospital stay. A total of 9,393 patients were included in the study. Univariate analysis showed that preoperative rehabilitation was significantly associated with postoperative length of hospital stay (coefficient: -1.61; 95% confidence interval: -2.42, -0.81; P <0.001). In addition, multivariate analysis showed preoperative rehabilitation to be associated with a significant decrease in postoperative length of hospital stay (coefficient=-1.38; 95% confidence interval: -2.19, -0.58; P =0.001). Preoperative rehabilitation may shorten length of hospital stay in elderly patients with lung cancer.

Facility staffing associated with potentially avoidable hospitalizations in nursing home residents in Japan: a retrospective cohort study.

BACKGROUND: Wide variations in facility staffing may lead to differences in care, and consequently, adverse outcomes such as hospitalizations. However, few studies focused on types of occupations. Therefore, we aimed to examine the association between a wide variety of facility staffing and potentially avoidable hospitalizations of nursing home residents in Japan. METHODS: In this retrospective cohort study using long-term care and medical insurance claims data in Ibaraki Prefecture from April 2018 to March 2019, we identified individuals aged 65 years and above who were newly admitted to nursing homes. In addition, facility characteristic data were obtained from the long-term care insurance service disclosure system. Subsequently, we conducted a multivariable Cox regression analysis and evaluated the association between facility staffing and potentially avoidable hospitalizations. RESULTS: A total of 2909 residents from 235 nursing homes were included. The cumulative incidence of potentially avoidable hospitalizations at 180 days was 14.2% (95% confidence interval [CI] 12.7-15.8). Facilities with full-time physicians (adjusted hazard ratio [HR]: 0.59, 95% CI: 0.37-0.94) and a higher number of dietitians (HR: 0.72, 95% CI: 0.54-0.97) were significantly associated with a lower likelihood of potentially avoidable hospitalizations. In contrast, having nurses or trained caregivers during the night shift (HR: 1.72, 95% CI: 1.25-2.36) and a higher number of care managers (HR: 1.37, 95% CI: 1.03-1.83) were significantly associated with a high probability of potentially avoidable hospitalizations. CONCLUSIONS: We revealed that variations in facility staffing were associated with potentially avoidable hospitalizations. The results suggest that optimal allocation of human resources, such as dietitians and physicians, may be essential to reduce potentially avoidable hospitalizations. To provide appropriate care to nursing home residents, it is necessary to establish a system to effectively allocate limited resources. Further research is warranted on the causal relationship between staff allocation and unnecessary hospitalizations, considering the confounding factors.

Frailty and occupational falls among older Japanese workers: An Internet-based cross-sectional study.

OBJECTIVES: Occupational falls are a major problem for older workers, especially those in the tertiary industry. Recently, it has been suggested that frailty is associated with occupational falls, but it is unclear whether this holds true for older workers in the tertiary industry. This study examined the relationship between frailty and occupational falls among older workers in the tertiary industry. METHODS: This was an Internet-based cross-sectional study. We recruited 5000 older workers (age, 60-75 years) employed in the tertiary industry who were registered with an Internet research company. Frailty was assessed using the Frailty Screening Index's five items, and participants were classified into robust, pre-frailty, or frailty groups. Occupational falls were defined as falls experienced in the past 12 months while at work. The relationship between frailty and occupational falls was analyzed by logistic regression analysis. RESULTS: It was found that 6.1% of participants had experienced at least one occupational fall in the past 12 months. On the multivariate analysis, the adjusted odds ratio (aOR) for falls was higher with pre-frailty (aOR: 1.95, 95% confidence interval: 1.30-2.94, P = .001) and frailty (aOR: 4.26, 95% confidence interval: 2.74-6.65, P < .001) compared with robust. Similar results were obtained when the outcome was occupational falls with injury. CONCLUSION: Our findings suggest that frailty is associated with occupational falls among older workers in tertiary industries. We recommend that employers introduce frailty screening, and consider countermeasures based on the screening results to prevent occupational falls among older workers.

Evaluation of the Effectiveness and Use of Anti-Methicillin-Resistant Staphylococcus aureus Agents for Aspiration Pneumonia in Older Patients Using a Nationwide Japanese Administrative Database.

Studies indicated potential harm from empirical broad-spectrum therapy. A recent study of hospitalizations for community-acquired pneumonia suggested that empirical anti-methicillin-resistant Staphylococcus aureus (MRSA) therapy was associated with an increased risk of death and other complications. However, limited evidence supports empirical anti-MRSA therapy for older patients with aspiration pneumonia. In a nationwide Japanese database, patients aged ≥65 years on admission with aspiration pneumonia were analyzed. Patients were divided based on presence of respiratory failure and further sub-categorized based on their condition within 3 days of hospital admission, either receiving a combination of anti-MRSA agents and other antibiotics, or not using MRSA agents. An inverse probability weighting method with estimated propensity scores was used. Out of 81,306 eligible patients, 55,098 had respiratory failure, and 26,208 did not. In the group with and without respiratory failure, 0.93% and 0.42% of the patients, respectively, received anti-MRSA agents. In patients with respiratory failure, in-hospital mortality (31.38% vs. 19.03%, p < 0.001), 30-day mortality, and 90-day mortality were significantly higher, and oxygen administration length was significantly longer in the anti-MRSA agent combination group. Anti-MRSA agent combination use did not improve the outcomes in older patients with aspiration pneumonia and respiratory failure, and should be carefully and comprehensively considered.

Effect of Early Postoperative Rehabilitation on Length of Hospital Stay after Robot-assisted Radical Prostatectomy.

Objectives: : This study assessed how early postoperative rehabilitation interventions affected the duration of hospital stay in patients with prostate cancer who had radical prostatectomy with robotic assistance. Methods: : From the Japanese Diagnosis Procedure Combination database, we extracted case data for patients discharged between April 2014 and March 2020. Patients were recognized by code C61 from the International Classification of Diseases, 10th Edition. We ran a multilevel linear regression analysis to investigate the impact of early rehabilitation on the duration of hospital stay. Results: : There were 2151 participants in the trial. In patients with prostate cancer who had resection utilizing robotic-assisted devices, early rehabilitation was related to a substantial decrease in duration of hospital stay (coefficient, -0.86; 95% CI, -1.64 to -0.07; P=0.032). Conclusions: : Early postoperative rehabilitation may contribute to shorter hospital stays in patients with prostate cancer at high risk of both postoperative complications and a decline in their ability to perform activities of daily living.

Clinical characteristics in patients with non-alcoholic steatohepatitis in Japan: a case-control study using a 5-year large-scale claims database.

OBJECTIVES: To examine the clinical characteristics of patients with non-alcoholic steatohepatitis (NASH) and associated comorbidities. DESIGN: A case-control study using the national health insurance and the long-term elderly health insurance claims database. SETTING: Eligible patients diagnosed with NASH (ICD-10 K-75.8, other inflammatory liver disease or K-76.0, other fatty liver) between April 2015 and March 2020 were included. PARTICIPANTS: Patients who met the diagnostic definitions for NASH (n=545) were matched with non-NASH controls (n=185 264) and randomly selected according to sex, birth year and residential area. INTERVENTIONS: No interventions were made. PRIMARY AND SECONDARY OUTCOME MEASURES: ORs were estimated for the relationship between patient background, such as age and sex, body mass index (BMI), NASH-related comorbidities and lifestyle-related diseases. RESULTS: In total, 545 patients with NASH (38.3% men) and 185 264 non-NASH controls (43.2% men) were identified, with median ages of 68 (IQR 63.0-75.0) and 65 (IQR 44.0-74.0) years, respectively. BMI was significantly higher in patients with NASH than in controls (25.8 kg/m2 vs 22.9 kg/m2, p<0.001). The proportions of women, patients with hypertension, patients with dyslipidaemia and patients with type 2 diabetes were higher in the NASH group. In addition, NASH was associated with an increased risk of hepatic cirrhosis (OR 28.81 (95% CI 21.79 to 38.08)), followed by liver cancer (OR 18.38 (95% CI 12.56 to 26.89)). There was no significant association between NASH and risk for depression (OR 1.11 (95% CI 0.87 to 1.41)), insomnia (OR 1.12 (95% CI 0.94 to 1.34)) or chronic kidney diseases (OR 0.81 (95% CI 0.58 to 1.12)). CONCLUSIONS: In the daily medical care of patients, it is necessary to consider sex and age differences and to pay close attention to the risk of liver cancer, as well as other lifestyle-related comorbidities associated with NASH.

Is Drosophila Dpp/BMP morphogen spreading required for wing patterning and growth?

Secreted signaling molecules act as morphogens to control patterning and growth in many developing tissues. Since locally produced morphogens spread to form a concentration gradient in the surrounding tissue, spreading is generally thought to be the key step in the non-autonomous actions. Here, we review recent advances in tool development to investigate morphogen function using the role of decapentaplegic (Dpp)/bone morphogenetic protein (BMP)-type ligand in the Drosophila wing disc as an example. By applying protein binder tools to distinguish between the roles of Dpp spreading and local Dpp signaling, we found that Dpp signaling in the source cells is important for wing patterning and growth but Dpp spreading from this source cells is not as strictly required as previously thought. Given recent studies showing unexpected requirements of long-range action of different morphogens, manipulating endogenous morphogen gradients by synthetic protein binder tools could shed more light on how morphogens act in developing tissues.