Intravascular imaging methods for venous disorders

The purposes are to assess the problems associated with intravascular imaging methods such as angioscopy and intravascular ultrasound (IVUS) and to evaluate their efficacy through the results of our observations. A total of 54 limbs in 53 patients, 50 patients with chronic venous insufficiency and 3 patients with deep vein thrombosis, were diagnosed and operated on using angioscopy (Olympus OES, order made type) and IVUS (Endosonics, model 82700). The imaging catheters were inserted through a branch of the long saphenous vein and the valves and the intraluminal views were observed. By angioscopy, intraluminal views were clearly observed in 98% of all lesions. However, observation became more difficult in iliac veins compared to in femoral and in long saphenous veins (p<0.01). Venous wall and thrombus were detected more by IVUS than by angioscopy (p<0.01), but only 21 valves (24%) were visualized by IVUS among the 88 valves observed by angioscopy. The intravascular imaging method of angioscopy is more suitable for observing valves and intraluminal views compared with IVUS, whereas IVUS is more suitable for observing the cross-sectional venous wall.     

Repeated unconsciousness due to chronic carbon monoxide poisoning in an older patient: a case report

Objective: Although much is known about acute carbon monoxide (CO) poisoning, little is known about chronic CO poisoning. Chronic CO poisoning is often diagnosed based on the patient’s living environment and medical history. Herein, we report the case of an older patient who presented with repeated unconsciousness due to chronic CO poisoning.Case presentation: A 90-year-old man was brought to the emergency department after being found at home with a disturbance of consciousness. Arterial blood gas measurements in room air revealed a carboxyhemoglobin level of 18.0%. Impaired consciousness was caused by chronic CO poisoning. The patient received high-flow oxygen therapy, which promptly improved his condition. According to his family, briquette kotatsu was the cause of chronic CO poisoning.Conclusion: Although high-flow oxygen therapy has been said to be less effective than hyperbaric oxygen therapy in CO poisoning treatment, recent studies have demonstrated that high-flow oxygen has similar effects and benefits. Thus, in institutions that do not have hyperbaric oxygen, high-flow oxygen may be sufficient to treat patients with CO poisoning, as seen in the present case. It should be noted that briquette kotatsu can lead to CO poisoning. This case highlights the need for clinicians to consider patients’ living conditions.     

Target epitopes of HTLV-1 recognized by class I MHC-restricted cytotoxic T lymphocytes in patients with myelopathy and spastic paraparesis and infected patients with autoimmune disorders

Human T-cell lymphotropic virus type I (HTLV-1) causes adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The different patterns of clinical diseases are thought to be linked to immunogenetic host factors. A variety of autoimmune diseases, such as Sj?gren's syndrome, have been reported in persons infected with HTLV-1, although the precise relationship between these disorders and HTLV-1 infection remains unknown. There is no report on the repertoire of HTLV-1-specific CD8+ T-cells in HAM/TSP patients or carriers with autoimmune diseases, both characterized by an abnormal immune state. In this study, to characterize HTLV-1-specific CD8+ T-cells in asymptomatic HTLV-1 carriers, HAM/TSP patients and carriers with autoimmune diseases, we examined the frequency and diversity of HTLV-1-specific CD8+ T-cells using HTLV-1 tetramers. HTLV-1 Env-specific CD8+ T-cells were significantly more frequent in HAM/TSP and carriers with autoimmune diseases compared with asymptomatic HTLV-1 carriers, while the frequency of HTLV-1 Tax-specific CD8+ T-cells was not significantly different among them. CD8+ cells binding to HTLV-1 Tax tetramers in carriers with autoimmune diseases were significantly reduced compared with HAM/TSP patients. This study demonstrates the importance of CD8+ T-cells recognizing HTLV-1 Env-tetramers in HAM/TSP patients and carriers with autoimmune diseases, thereby suggesting that the diversity, frequency and repertoire of HTLV-1 Env-specific CD8+ T-cell clones may be related to the hyperimmune response in HAM/TSP and carriers with autoimmune diseases, although different immunological mechanisms may mediate the hyperimmunity in these conditions.     

The Association of Work-related Stress According to the Demand–Control Model With Aggravation of Pre-existing Disease During the First State of COVID-19 Emergency in Japan

BackgroundThe job environment has changed a lot during the period of the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to investigate the association between work-related stress and aggravation of pre-existing disease in workers during the first state of COVID-19 emergency in Japan.MethodsData were obtained from a large internet survey conducted between August 25 and September 30, 2020 in Japan. Participants who reported that they had a job as well as current history of disease(s) (ie, pre-existing conditions) were included (n = 3,090). Aggravation of pre-existing disease during the state of emergency was self-reported. Work-related stress from April 2020 (since the state of COVID-19 emergency) was assessed according to a job demand–control model. Multivariable logistic regression models were used to analyze the association.ResultsAggravation of pre-existing diseases was reported by 334 participants (11%). The numbers of participants with high demand and low control were 112 (18%) and 100 (14%), respectively. Compared to medium demand, high demand was significantly associated with aggravation of pre-existing diseases (odds ratio 1.77; 95% confidence interval, 1.30–2.42). Low control compared to medium control was also significantly associated with aggravation of pre-existing diseases (odds ratio 1.39; 95% confidence interval, 1.02–1.92).ConclusionWork-related stress during the first state of COVID-19 emergency was associated with aggravation of pre-existing disease during that period.Key words: work-related stress, pre-existing disease, job demand, job control, COVID-19     

Sulphur metabolism in colon cancer tissues: a case report and literature review

Sulphur-containing compounds have been linked to colorectal cancer by factors such as the presence of methyl mercaptan in intestinal gas and long-term dietary intake associated with sulphur-metabolizing microbiota. Therefore, this current case report hypothesized that active sulphur metabolism in colorectal cancer results in the formation of sulphur compounds in the intestine and, thus, examined sulphur metabolites possibly associated with sulphur respiration in colon cancer tissues. The patient was a 73-year-old female that underwent laparoscopic right hemicolectomy for ascending colon cancer. During the surgery, colon cancer tissues and normal intestinal mucosa samples were collected. After optimizing the sample concentrations for homogenization (pre-treatment), the samples were stabilized using a hydroxyphenyl-containing derivative and the relevant metabolites were quantified using liquid chromatography with tandem mass spectrometry. The results showed that cysteine persulfide and cysteine trisulfide levels were higher in colon cancer tissues than in normal mucosal tissues. Thus, sulphur metabolism, possibly sulphur respiration, is enhanced in colon cancer tissues.     

Effects of Immediate and Delayed Cementations for CAD/CAM Resin Block after Alumina Air Abrasion on Adhesion to Newly Developed Resin Cement

The purpose of this study was to evaluate the effect of one week of Computer-aided design/Computer-aided manufacturing (CAD/CAM) crown storage on the μTBS between resin cement and CAD/CAM resin composite blocks. The micro-tensile bond strength (μTBS) test groups were divided into 4 conditions. There are two types of CAD/CAM resin composite blocks, namely A block and P block (KATANA Avencia Block and KATANA Avencia P Block, Kuraray Noritake Dental, Tokyo, Japan) and two types of resin cements. Additionally, there are two curing methods (light cure and chemical cure) prior to the μTBS test—Immediate: cementation was performed immediately; Delay: cementation was conducted after one week of storage in air under laboratory conditions. The effect of Immediate and Delayed cementations were evaluated by a μTBS test, surface roughness measurements, light intensity measurements, water sorption measurements and Scanning electron microscope/Energy dispersive X-ray spectrometry (SEM/EDS) analysis. From the results of the μTBS test, we found that Delayed cementation showed significantly lower bond strength than that of Immediate cementation for both resin cements and both curing methods using A block. There was no significant difference between the two types of resin cements or two curing methods. Furthermore, water sorption of A block was significantly higher than that of P block. Within the limitations of this study, alumina air abrasion of CAD/CAM resin composite restorations should be performed immediately before bonding at the chairside to minimize the effect of humidity on bonding.     

Histone methyltransferase SUV420H1/KMT5B contributes to poor prognosis in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) has a high rate of recurrence and poor prognosis, even after curative surgery. Multikinase inhibitors have been applied for HCC patients, but their effect has been restricted. This study aims to clarify the clinical impact of SUV420H1/KMT5B, one of the methyltransferases for histone H4 at lysine 20, and elucidate the novel mechanisms of HCC progression. We retrospectively investigated SUV420H1 expression using HCC clinical tissue samples employing immunohistochemical analysis (n = 350). We then performed loss-of-function analysis of SUV420H1 with cell cycle analysis, migration assay, invasion assay and RNA sequence for Gene Ontology (GO) pathway analysis in vitro, and animal experiments with xenograft mice in vivo. The SUV420H1-high-score group (n = 154) had significantly poorer prognosis for both 5-year overall and 2-year/5-year disease-free survival than the SUV420H1-low-score group (n = 196) (p < 0.001 and p < 0.05, respectively). The SUV420H1-high-score group had pathologically larger tumor size, more tumors, poorer differentiation, and more positive vascular invasion than the SUV420H1-low-score group. Multivariate analysis demonstrated that SUV420H1 high score was the poorest independent factor for overall survival. SUV420H1 knockdown could suppress cell cycle from G1 to S phase and cell invasion. GO pathway analysis showed that SUV420H1 contributed to cell proliferation, cell invasion, and/or metastasis. Overexpression of SUV420H1 clinically contributed to poor prognosis in HCC, and the inhibition of SUV420H1 could repress tumor progression and invasion both in vitro and in vivo; thus, further analyses of SUV420H1 are necessary for the discovery of future molecularly targeted drugs.     

Long-term experience with tepotinib in Japanese patients with MET exon 14 skipping NSCLC from the Phase II VISION study

Tepotinib is a highly selective MET tyrosine kinase inhibitor (TKI) that has demonstrated robust and durable clinical activity in patients with MET exon 14 (METex14) skipping non–small-cell lung cancer (NSCLC). In the Phase II VISION study, patients received oral tepotinib 500 mg once daily. The primary endpoint was an objective response by an independent review committee (IRC) according to RECIST v1.1 criteria. The secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Here we report the analysis of the efficacy and safety of tepotinib in all Japanese patients with advanced METex14 skipping NSCLC from VISION (n = 38) with >18 months' follow-up. The median age of the Japanese patients was 73 years (range 63–88), 39.5% of patients were ≥75 years old, 68.4% were male, 55.3% had a history of smoking, 76.3% had adenocarcinoma, and 10.5% of patients had known brain metastases at baseline. Overall, the objective response rate (ORR) was 60.5% (95% confidence interval (CI): 43.4, 76.0) with a median DOR of 18.5 months (95% CI: 8.3, not estimable). ORR in treatment-naïve patients (n = 18) was 77.8% (95% CI: 52.4, 93.6), and in patients aged ≥75 years (n = 15), ORR was 73.3% (95% CI: 44.9, 92.2). The most common treatment-related adverse event (AE) with any grade was blood creatinine increase (65.8%), which resolved following tepotinib discontinuation. Other common treatment-related AEs were peripheral edema (60.5%), hypoalbuminemia (34.2%), diarrhea (28.9%), and nausea (15.8%). In summary, tepotinib demonstrated robust and durable clinical activity irrespective of age or therapy line, with a manageable safety profile in Japanese patients with METex14 skipping NSCLC enrolled in VISION.