Blood pressure classification using the Japanese Society of Hypertension Guidelines for the Management of Hypertension and cardiovascular events among young to middle-aged working adults.

The Japanese Society of Hypertension updated guidelines for hypertension management (JSH2019), changing the blood pressure (BP) classification. However, evidence is sparse regarding the association of the classification with cardiovascular disease (CVD) events among young to middle-aged workers in Japan. We examined this issue using longitudinal data from Japan Epidemiology Collaboration on Occupational Health Study with a prospective cohort design. Participants were 81,876 workers (aged 20-64 years) without taking antihypertensive medication at baseline. BP in 2011 or 2010 was used as exposure. CVD events that occurred from 2012 to 2021 were retrieved from a within-study registry. Cox regression was used to calculate multivariable-adjusted hazard ratios of CVD events. During 0.5 million person-years of follow-up, 334 cardiovascular events, 75 cardiovascular deaths, and 322 all-cause deaths were documented. Compared with normal BP (systolic BP [SBP] < 120 mmHg and diastolic BP [DBP] < 80 mmHg), multivariable-adjusted hazard ratios (95% confidence intervals) of cardiovascular events were 1.98 (1.49-2.65), 2.10 (1.58-2.77), 3.48 (2.33-5.19), 4.12 (2.22-7.64), and 7.81 (3.99-15.30) for high normal BP (SBP120-129 mmHg and DBP < 80 mmHg), elevated BP (SBP130-139 mmHg and/or DBP80-89 mmHg), stage 1 hypertension (SBP140-159 mmHg and DBP90-99 mmHg), stage 2 hypertension (SBP160-179 mmHg and/or DBP100-109 mmHg), and stage 3 hypertension (SBP ≥ 180 mmHg and/or DBP ≥ 110 mmHg), respectively. The highest population attributable fraction was observed in elevated BP (17.8%), followed by stage 1 hypertension (14.1%). The present data suggest that JSH2019 may help identify Japanese workers at a higher cardiovascular risk.

Structural Elucidation and Prognostic Relevance of 297-11A-Sulfated Glycans in Ovarian Carcinoma.

Ovarian carcinoma is usually diagnosed at an advanced stage with peritoneal dissemination and/or lymph node metastasis, and the prognosis for such advanced carcinoma is very poor. Therefore, new biomarkers to predict patient prognosis are needed. Miyamoto et al. previously showed that keratan sulfate (KS) detected by the 5D4 monoclonal antibody was expressed in ovarian carcinoma. However, the detailed structure of such KS was not determined, and the biological significance of this finding remained to be clarified. We previously generated the 297-11A monoclonal antibody, which recognizes galactose (Gal)-6-O-sulfated N-acetyllactosamine (LacNAc) located at the nonreducing terminus. Because the 297-11A epitope overlaps with that of 5D4, here we chose to use the 297-11A antibody as a tool to analyze KS and related structures. We conducted immunohistochemical analysis of 98 ovarian carcinoma cases with 297-11A antibody combined with a series of glycosidases and performed mass spectrometry analysis of the human serous ovarian carcinoma cell line OVCAR-3 to deduce the glycan structure of 297-11A-sulfated glycans. We also performed western blot analysis to assess a potential association of 297-11A-sulfated glycans with the mucin core protein mucin 16 (MUC16; also known as cancer antigen 125 (CA125)). Finally, we examined the relationship between 297-11A expression and patient prognosis. Consequently, 297-11A-sulfated glycans were primarily expressed in serous and endometrioid carcinomas and poorly expressed in mucinous and clear cell carcinomas. We reveal that structurally, 297-11A-sulfated glycans expressed in ovarian carcinoma are O-glycans carrying partially sialylated, Gal-6-O-sulfated LacNAc and that these glycans are likely displayed on MUC16 mucin core proteins. Of clinical importance is that expression of 297-11A-sulfated glycans correlated with shorter progression-free survival in patients. Thus, 297-11A-sulfated glycans may serve as a predictor of ovarian carcinoma recurrence.

Galectin-10 in serum extracellular vesicles reflects asthma pathophysiology.

BACKGROUND: Novel biomarkers (BMs) are urgently needed for bronchial asthma (BA) with various phenotypes and endotypes. OBJECTIVE: We sought to identify novel BMs reflecting tissue pathology from serum extracellular vesicles (EVs). METHODS: We performed data-independent acquisition of serum EVs from 4 healthy controls, 4 noneosinophilic asthma (NEA) patients, and 4 eosinophilic asthma (EA) patients to identify novel BMs for BA. We confirmed EA-specific BMs via data-independent acquisition validation in 61 BA patients and 23 controls. To further validate these findings, we performed data-independent acquisition for 6 patients with chronic rhinosinusitis without nasal polyps and 7 patients with chronic rhinosinusitis with nasal polyps. RESULTS: We identified 3032 proteins, 23 of which exhibited differential expression in EA. Ingenuity pathway analysis revealed that protein signatures from each phenotype reflected disease characteristics. Validation revealed 5 EA-specific BMs, including galectin-10 (Gal10), eosinophil peroxidase, major basic protein, eosinophil-derived neurotoxin, and arachidonate 15-lipoxygenase. The potential of Gal10 in EVs was superior to that of eosinophils in terms of diagnostic capability and detection of airway obstruction. In rhinosinusitis patients, 1752 and 8413 proteins were identified from EVs and tissues, respectively. Among 11 BMs identified in EVs and tissues from patients with chronic rhinosinusitis with nasal polyps, 5 (including Gal10 and eosinophil peroxidase) showed significant correlations between EVs and tissues. Gal10 release from EVs was implicated in eosinophil extracellular trapped cell death in vitro and in vivo. CONCLUSION: Novel BMs such as Gal10 from serum EVs reflect disease pathophysiology in BA and may represent a new target for liquid biopsy approaches.

Diabetes, Prediabetes, and the Risk of a Composite Outcome of Long-term Sickness Absence and Pre-retirement Death Due to Physical Disorders.

BACKGROUND: Diabetes and prediabetes have been linked with morbidity or mortality from cardiovascular disease, cancer, or other physical disorders among working-age populations, but less is known about outcomes directly related to labor loss (eg, Tlong-term sickness absence [LTSA] or pre-retirement death due to physical disorders).This prospective study aimed to examine the association of diabetes and prediabetes with the risk of a composite outcome of LTSA and pre-retirement death due to physical disorders. The present study also examined the associations of severe outcomes (LTSA or death) due to specific physical disorders or injuries/external causes in relation to diabetes and prediabetes. METHODS: Data were derived from the Japan Epidemiology Collaboration on Occupational Health study. A total of 60,519 workers from 12 companies were followed for 8 years. Diabetes and prediabetes were defined based on the American Diabetes Association criteria. A Cox proportional hazards regression model was used to examine the association between diabetes/prediabetes and severe outcomes due to physical disorders or injuries/external causes. RESULTS: The adjusted hazard ratios of severe outcomes due to all physical disorders were 1.22 (95% confidence interval [CI], 1.02-1.45) and 2.32 (95% CI, 2.04-2.64) for prediabetes and diabetes, respectively. In cause-specific analyses, an increased risk was observed for severe outcomes due to cancers, cardiovascular diseases, diseases of the musculoskeletal system, and injuries/external causes in relation to either or both diabetes and prediabetes. CONCLUSION: Diabetes and prediabetes were associated with an increased risk of severe outcomes due to physical disorders or injuries/external causes among Japanese workers.

Hemodynamic and morphological differences in cerebral aneurysms between before and after rupture.

OBJECTIVE: Although it has been proposed that aneurysm morphology is different after rupture, detailed research of the morphological changes using 3D imaging acquired before and after rupture has not been conducted because of the difficulty of data collection. Similarly, hemodynamic changes due to morphological alterations after rupture have not been analyzed. The aim of this study was to investigate the changes in morphology and hemodynamics observed after aneurysm rupture. METHODS: For 21 cerebral aneurysms (21 patients) that ruptured during observation, 3D geometry of the aneurysms and parent arteries were reconstructed based on the angiographic images before and after their rupture. In addition, using the reconstructed geometry, blood flow was simulated by computational fluid dynamics (CFD) analysis. Morphological and hemodynamic parameters were calculated both before and after rupture, and their changes from before to after were compared. RESULTS: In the morphological parameters, statistically significantly higher values were observed after rupture in height (before: 5.5 ± 2.1 mm, after: 6.1 ± 2.0 mm; p < 0.0001), aspect ratio (p = 0.002), aneurysm volume (p = 0.04), and undulation index (p = 0.005). In terms of hemodynamic changes, the mean normalized wall shear stress (NWSS) decreased significantly (before: 5.4 × 10-1 ± 2.9 × 10-1, after: 4.4 × 10-1 ± 2.8 × 10-1; p < 0.001) as well as the other NWSS parameters, including maximum and minimum NWSS, which were associated with stagnant flow due to the morphological changes after rupture. CONCLUSIONS: Aneurysm morphology was found to change after rupture into an elongated and irregular geometry, accompanied by an increase in aneurysm volume. These morphological changes were also associated with statistically significant hemodynamic alterations that produced low wall sheer stress by stagnant flow. The authors' results also provide the opportunity to explore and develop a risk evaluation method for aneurysm rupture based on prerupture morphology and hemodynamics by further exploration in this direction.

Successful second-line treatment with cabozantinib for hepatocellular carcinoma harboring cytoplasmic mesenchymal-epithelial transition factor amplification.

A 72-year-old man with metastatic hepatocellular carcinoma previously received first-line systemic therapy with atezolizumab plus bevacizumab. His disease was judged to be progressing 5 months after treatment initiation. Comprehensive genomic profiling revealed cytoplasmic mesenchymal-epithelial transition factor amplification. On the basis of an expert panel's recommendation, he received cabozantinib as second-line therapy. The tumors shrank markedly and continued to shrink 6 months after treatment. Comprehensive genomic profiling could provide useful information for selecting effective second-line treatments for patients with hepatocellular carcinoma after first-line immunotherapy.

Development of Machine Learning Model for Selecting the 1st Coil in the Treatment of Cerebral Aneurysms by Coil Embolization.

To achieve good treatment outcomes in coil embolization for cerebral aneurysms, it is important to select an appropriate 1st coil for each aneurysm since it serves as a frame to support the subsequent coils to be deployed. However, its selection as appropriate size and length from a wide variety of lineups is not easy, especially for inexperienced neurosurgeons. We developed a machine learning model (MLM) to predict the optimal size and length of the 1st coil by learning information on patients and aneurysms that were previously treated with coil embolization successfully. The accuracy rates of the MLM for the test data were 86.3% and 83.4% in the prediction of size and length, respectively. In addition, the accuracy rates for the 30 cases showed good prediction by the MLM when compared with two different skilled neurosurgeons. Although the accuracy rate of the well-experienced neurosurgeon is similar to MLM, the inexperienced neurosurgeon showed a worse rate and can benefit from the method.Clinical Relevance- The developed MLM has the potential to assist in the selection of the 1st coil for aneurysms. A technically and cost efficient supply chain in the treatment of aneurysms may also be achieved by MLM application.

Novel Utility of Leucine-Rich Alpha-2-Glycoprotein as a Biomarker in Ulcerative Colitis: A Predictor of Endoscopic Remission Independent of Symptoms.

Introduction: Leucine-rich alpha-2-glycoprotein (LRG) is a potential biomarker for disease activity and reflects mucosal healing in patients with ulcerative colitis (UC). However, only a few studies have described a detailed sensitivity analysis of LRG in predicting mucosal healing in patients. This study aimed to evaluate the association between LRG and the endoscopic activity of UC and its predictability for mucosal healing and explore the utility and clinical application of LRG. Methods: The diagnostic accuracy of biomarkers, including LRG, in predicting the endoscopic activity of UC was evaluated. All consecutive patients who underwent total colonoscopy between April 2021 and September 2022 were included. The Mayo endoscopic subscore (MES) was used for assessing endoscopic activity. Furthermore, endoscopic remission was defined as an MES of ≤1. Clinical activity was evaluated based on stool frequency and bloody stool. Receiver operating characteristic curve analysis and binary logistic regression were performed to assess the diagnostic accuracy of the biomarkers. We evaluated LRG trends and treatment response in patients with MES ≥2 who underwent induction therapy. Results: This study comprised 214 patients. The proportions of endoscopically and clinically active patients were 33.6% and 49.1%, respectively. LRG had an area under the curve (AUC) of 0.856, with a higher diagnostic accuracy than other biomarkers, such as C-reactive protein, leukocyte, neutrophil, platelet, and albumin. The cutoff value for LRG was 15.6 µg/mL (sensitivity, 72.2%; specificity, 86.6%). Using the MES, patients with higher scores had higher LRG levels than those with lower scores. The cutoff value, AUC, sensitivity, and specificity varied with a higher AUC for left-sided colitis and pancolitis than for proctitis. Logistic regression analysis showed that LRG was an independent predictor of endoscopic remission using multivariate analysis, even with the factor of clinical activity. The change ratio of LRG pre- and post-treatment was statistically significant in the higher LRG group. Conclusion: LRG reflected endoscopic activity independently, regardless of clinical symptoms. An LRG below the cutoff value could indicate a significantly low probability of endoscopic activity in asymptomatic patients, and follow-up endoscopy (not for cancer screening) may be unnecessary. Furthermore, a higher LRG level might be more useful as an indicator of treatment efficacy.

Metabolic syndrome and the risk of severe cancer events: a longitudinal study in Japanese workers.

BACKGROUND: Metabolic syndrome (MetS) is associated with cancer risk; however, little is known regarding its relationship with the risk of cancer-related premature death and long-term sick leave (LTSL), which can lead to a substantial loss in working years. The present study aimed to quantify the all-site and site-specific associations between MetS and the risk of severe cancer events (a composite outcome of LTSL and mortality due to cancer) in a large working population in Japan. METHODS: We recruited 70,875 workers (59,950 men and 10,925 women), aged 20-59 years, who attended health check-ups in 2011 (10 companies) and 2014 (2 companies). All workers underwent follow up for severe cancer events until March 31, 2020. MetS was defined in accordance with the Joint Interim Statement. Cox regression models were used to quantify the association between baseline MetS and severe cancer events. RESULTS: During 427,379 person-years of follow-up, 523 participants experienced the outcome consisting of 493 LTSLs of which 124 eventually resulted in death, and 30 deaths without taking LTSL. The adjusted hazard ratios (HR) (95% confidence intervals [CI]) for composite severe events due to all-site, obesity-related, and non-obesity-related cancer among those with vs. without MetS were 1.26 (1.03, 1.55), 1.37 (1.04, 1.82), and 1.15 (0.84, 1.56), respectively. In cancer site-specific analyses, MetS was associated with an increased risk of severe events due to pancreatic cancer (HR, 2.06; 95% CI, 0.99-4.26). When mortality was treated solely as the endpoint, the association was significant for all-site (HR, 1.58; 95% CI, 1.10-2.26), and obesity-related (HR, 1.59; 95% CI, 1.00-2.54) cancer. Additionally, a greater number of MetS components was associated with a greater risk of both severe cancer events and cancer-related mortality (P trend < 0.05). CONCLUSION: Among Japanese workers, MetS was associated with an increased risk of severe cancer events, especially those due to obesity-linked cancer.

Secondary subcutaneous abscess due to mixed infections by Peptoniphilus olsenii and Gleimia europaea after COVID-19.

This report described a rare case of subcutaneous anaerobic bacterial abscess due to Peptoniphilus olsenii and Gleimia europaea after COVID-19. The patient received incision and drainage of the abscess and antibiotics, thereby achieving recovery. Immunodeficiency related to COVID-19 and its treatment might contribute to secondary skin and subcutaneous bacterial infections.

Metabolic Syndrome and the Increased Risk of Medically Certified Long-term Sickness Absence: A Prospective Analysis Among Japanese Workers.

BACKGROUND: Metabolic syndrome (MetS) has been associated with various chronic diseases that may lead to long-term sickness absence (LTSA), but there is lacking information on the direct association between MetS and LTSA. The present study aimed to investigate the all-cause and cause-specific associations between MetS and the risk of medically certified LTSA among Japanese workers. METHODS: We recruited 67,403 workers (57,276 men and 10,127 women), aged 20-59 years from 13 companies in Japan during their health check-ups in 2011 (11 companies) and 2014 (2 companies), and we followed them for LTSA events (≥30 consecutive days) until March 31, 2020. MetS was defined according to the Joint Interim Statement. A Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and its 95% confidence intervals (CIs) for LTSA associated with MetS and its components. RESULTS: During 408,324 person-years of follow-up, 2,915 workers experienced LTSA. The adjusted HR for all-cause LTSA was 1.54 (95% CI, 1.41-1.68) among those with MetS compared to those without MetS. In cause-specific analysis, HRs associated with MetS significantly increased for LTSA due to overall physical disorders (1.76); cardiovascular diseases (3.16); diseases of the musculoskeletal system and connective tissue (2.01); cancers (1.24); obesity-related cancers (1.35); mental, behavioral, and neurodevelopmental disorders (1.28); reaction to severe stress and adjustment disorders (1.46); and external causes (1.46). The number of MetS components were also significantly associated with increased LTSA risk. CONCLUSION: MetS was associated with an increase in the risk of LTSA due to various diseases among Japanese workers.

Large-cell Neuroendocrine Carcinoma of the Lung with Carcinoid Syndrome.

A 76-year-old woman was admitted to our hospital for refractory diarrhea with a poor antidiarrheal effect. Chest and abdominal computed tomography revealed a 24×22-mm mass in the left upper lobe of lung and multiple masses in the liver. Urine 5-Hydroxy indol acetic acid was markedly elevated. A liver biopsy revealed large-cell neuroendocrine carcinoma with serotonin production, suggestive of a lung origin, and a lung biopsy revealed combined large-cell neuroendocrine carcinoma and squamous cell carcinoma. Therefore, we made a definitive diagnosis of carcinoid syndrome caused by large-cell neuroendocrine carcinoma of the lung. Although chemotherapy was performed after diagnosis, the patient died 50 days postadmission.

Next-generation proteomics of serum extracellular vesicles combined with single-cell RNA sequencing identifies MACROH2A1 associated with refractory COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is widespread; however, accurate predictors of refractory cases have not yet been established. Circulating extracellular vesicles, involved in many pathological processes, are ideal resources for biomarker exploration. METHODS: To identify potential serum biomarkers and examine the proteins associated with the pathogenesis of refractory COVID-19, we conducted high-coverage proteomics on serum extracellular vesicles collected from 12 patients with COVID-19 at different disease severity levels and 4 healthy controls. Furthermore, single-cell RNA sequencing of peripheral blood mononuclear cells collected from 10 patients with COVID-19 and 5 healthy controls was performed. RESULTS: Among the 3046 extracellular vesicle proteins that were identified, expression of MACROH2A1 was significantly elevated in refractory cases compared to non-refractory cases; moreover, its expression was increased according to disease severity. In single-cell RNA sequencing of peripheral blood mononuclear cells, the expression of MACROH2A1 was localized to monocytes and elevated in critical cases. Consistently, single-nucleus RNA sequencing of lung tissues revealed that MACROH2A1 was highly expressed in monocytes and macrophages and was significantly elevated in fatal COVID-19. Moreover, molecular network analysis showed that pathways such as "estrogen signaling pathway," "p160 steroid receptor coactivator (SRC) signaling pathway," and "transcriptional regulation by STAT" were enriched in the transcriptome of monocytes in the peripheral blood mononuclear cells and lungs, and they were also commonly enriched in extracellular vesicle proteomics. CONCLUSIONS: Our findings highlight that MACROH2A1 in extracellular vesicles is a potential biomarker of refractory COVID-19 and may reflect the pathogenesis of COVID-19 in monocytes.

Impact of treatment line on risks and benefits of immune checkpoint inhibitor in patients with advanced non-small cell lung cancer and interstitial lung disease: a systematic review and meta-analysis of cohort studies.

Background: There is no clear consensus regarding the safety and efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC) and pre-existing interstitial lung disease (ILD). We aimed to elucidate the impact of ICIs on pre-existing ILD. Methods: We systematically queried PubMed-MEDLINE, Embase-Scopus, and ISI Web of Science databases up to January 10, 2022. The pooled any-grade and grade 3-5 ICI-associated pneumonitis (ICIP) rate and objective response rate (ORR) in patients with pre-existing ILD were mainly evaluated. The relative risk (RR) was also evaluated for pre-existing ILD and usual interstitial pneumonia (UIP) patterns. Sensitivity and subgroup analyses were performed to assess the heterogeneity. Results: In total, 17 studies involving 5,529 patients were included in the meta-analysis. The pooled ICIP rate was 30% [95% confidence interval (CI): 24-36%]; it was found to be significantly higher in patients with pre-existing ILD relative to those without (RR =3.05, 95% CI: 2.53-3.69; I2=0.0%). The pooled grade 3-5 ICIP rate was 12% (95% CI: 9-15%); this was also significantly higher in patients with pre-existing ILD (RR =3.19, 95% CI: 2.32-4.38; I2=0.0%). According to subgroup analysis, these ICIP rates were not significantly different among the treatment lines (first, ≥ second, and mixed) (P=0.33) whereas the pooled ORR was 36% (95% CI: 24-48%; I2=53.7%) with a significant difference among the treatment lines (P=0.027). The pooled ICIP rate was independent of the UIP pattern (RR =1.06, 95% CI: 0.86-1.32; I2=0.0%). Conclusions: Overall, ICIs should be administered cautiously in patients with pre-existing ILD, regardless of the treatment line. Moreover, the risks of ICIP may outweigh ICI benefits, especially in second-or later-line treatment. These results need to be further confirmed by meta-analyses including more observational cohort studies in clinical setting.

Respiratory Impedance is Associated with Ventilation and Diffusing Capacity in Patients with Idiopathic Pulmonary Fibrosis Combined with Emphysema.

Purpose: Pulmonary fibrosis and emphysema result in relatively maintained ventilation and reduced diffusing capacity. This pulmonary functional impairment complicates the evaluation of pulmonary function in patients with combined pulmonary fibrosis and emphysema (CPFE). Therefore, a single and easy-to-use pulmonary function index to evaluate patients with CPFE warrants further studies. Respiratory impedance can easily be provided by oscillometry and might be a candidate index to evaluate pulmonary function in patients with CPFE. As a preliminary study to assess the utility of respiratory impedance, we investigated the associations of physiological indices, including respiratory impedance, in patients with idiopathic pulmonary fibrosis (IPF) with and without emphysema. Patients and Methods: This retrospective study evaluated patients with IPF who did and did not satisfy the diagnostic criteria of CPFE. All patients underwent oscillometry, spirometry, and diffusing capacity for carbon monoxide (DLCO). Correlations of the obtained physiological indices were analyzed. Results: In total, 47 patients were included (18 and 29 patients with CPFE and IPF, respectively). Respiratory reactance (Xrs) at 5 Hz (X5) in the inspiratory phase was associated with forced vital capacity (FVC) % predicted in patients with CPFE (rS=0.576, P=0.012) and IPF (rS=0.539, P=0.003). Inspiratory X5 positively correlated with DLCO % predicted only in patients CPFE (rS=0.637, P=0.004). Conclusion: Emphysema might associate Xrs with ventilation and diffusing capacity in patients with IPF and emphysema. Given the multiple correlations of Xrs with FVC and DLCO, this study warrants further studies to verify the utility of oscillometry in a large-scale study for patients with CPFE.

Ischemic Stroke Due to Heparin-induced Thrombocytopenia during Severe COVID-19 Infection.

A 53-year-old woman with severe coronavirus disease 2019 (COVID-19) pneumonia was admitted and treated with intravenous unfractionated heparin for thromboprophylaxis under general anesthesia with mechanical ventilation. She developed right hemiparesis after hospitalization due to a large hemorrhagic infarction. Her platelet count decreased from 243,000/µL at administration to 121,000/µL. Anti-platelet factor 4-heparin antibody testing was positive according to a latex immunoturbidimetric assay. She was therefore diagnosed with heparin-induced thrombocytopenia. We immediately stopped the heparin and started argatroban; the platelet count recovered, and thrombosis did not relapse. Physicians should consider heparin-induced thrombocytopenia as a cause of ischemic stroke in patients with COVID-19 infection.

Effects of different stent wire mesh densities on hemodynamics in aneurysms of different sizes.

BACKGROUND: Intracranial stents are used to treat aneurysms by diverting the blood flow from entering into the aneurysmal dome. Although delayed rupture is rare, clinical outcomes are extremely poor in such cases. Hemodynamics after stent deployment may be related to delayed rupture and a better understanding of the basic characteristics of pressure changes resulting from stent deployment is needed; therefore, this study investigated the relationships between hemodynamics in aneurysms of different sizes treated using stents of different wire mesh densities. METHODS: Using computational fluid dynamics analysis, parameters related to velocity, volume flow rate, pressure, and residual volume inside the aneurysm were evaluated in digital models of 5 basic aneurysms of differing sizes (Small, Medium, Medium-Large, Large, and Giant) and using 6 different types of stent (varying number of wires, stent pitch and wire mesh density) for each aneurysm. RESULTS: Regardless of the aneurysm size, the velocity inside the aneurysm and the volume flow rate into the aneurysm were observed to continuously decrease up to 89.2% and 78.1%, respectively, with increasing stent mesh density. In terms of pressure, for giant aneurysms, the pressure on the aneurysmal surface elevated to 10.3%, then decreased to 5.1% with increasing stent mesh density. However, in smaller aneurysms, this pressure continuously decreased with increasing stent mesh density. The flow-diverting effect of the stents was limited when a stent with low mesh density (under 20%) was used with a giant aneurysm. CONCLUSIONS: The present results indicate that the selection of appropriate stents according to aneurysm size may contribute to reduced risks of hemodynamic alternations related to stent deployment, which could reduce the incidence of delayed rupture.

Diabetes, prediabetes, and long-term sickness absence due to mental disorders: Japan Epidemiology Collaboration on Occupational Health Study.

OBJECTIVES: To investigate the association of diabetes and prediabetes with long-term sickness absence (LTSA) due to mental disorders or specific mental disorders. METHODS: A prospective cohort study was conducted using data from the Japan Epidemiology Collaboration on Occupational Health Study. A total of 62,065 workers who received health check-ups in 2011 (nine companies) or 2014 (two companies) and were followed up to March 31, 2020 were included in this study. Diabetes status was defined based on the American Diabetes Association criteria, and diabetes was differentiated into diabetes with/without anti-diabetic treatment for additional analysis. A Cox proportional hazards regression model was used to investigate these associations. RESULTS: During maximum 8-year follow-up period, 1024 participants underwent LTSA due to mental disorders. The adjusted hazard ratio (aHR) and corresponding 95% confidence interval (CI) of LTSA due to all mental disorders were 1.10 (0.88-1.38) and 1.45 (1.07-1.98) for prediabetes and diabetes, respectively. Diabetic individuals with/without treatment were both at a high risk of LTSA due to mental disorders. For specific mental disorders, diabetes was associated with a higher risk of LTSA due to reaction to severe stress and adjustment disorders (aHR = 3.02, 95% CI = 2.01-4.52) while it was marginally associated with LTSA due to depressive episode (aHR = 1.25, 95% CI = 0.98-1.60). Prediabetes was also associated with LTSA due to reaction to severe stress and adjustment disorders (aHR = 1.41, 95% CI = 1.08-1.84). CONCLUSIONS: The present study suggests the importance of screening diabetes status and providing psychological support for decreasing the risk of LTSA due to mental disorders within working populations.