Anti-SARS CoV-2 IgG in COVID-19 Patients with Hematological Diseases: A Single-center,Retrospective Study in Japan

Objective Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally. Although the relationship between anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies and COVID-19 severity has been reported, information is lacking regarding the seropositivity of patients with particular types of diseases, including hematological diseases. Methods In this single-center, retrospective study, we compared SARS-CoV-2 IgG positivity between patients with hematological diseases and those with non-hematological diseases. Results In total, 77 adult COVID-19 patients were enrolled. Of these, 30 had hematological disorders, and 47 had non-hematological disorders. The IgG antibody against the receptor-binding domain of the spike protein was detected less frequently in patients with hematological diseases (60.0%) than in those with non-hematological diseases (91.5%; p=0.029). Rituximab use was significantly associated with seronegativity (p=0.010). Conclusion Patients with hematological diseases are less likely to develop anti-SARS-CoV-2 antibodies than those with non-hematological diseases, which may explain the poor outcomes of COVID-19 patients in this high-risk group.     

Efficacy of hand-assisted laparoscopic surgery (HALS) in older adult patients (≥80 years) with primary colorectal cancer

BackgroundFrom 2004 to 2014, 821 colorectal cancer primary resections were conducted at our institution. Of these, 102 patients (12.4%) were older adults over 80 years old. underwent either the conventional laparotomy group (72 patients) or the hand-assisted laparoscopic surgery (HALS) group (30 patients).MethodsData were extracted for 102 patients over 80 years old who underwent primary resection for colorectal cancer and were divided into two groups: conventional laparotomy (CL) (n=72) and hand-assisted laparoscopy (n=30). Pre-operative characteristics and outcomes were compared.ResultsBaseline characteristics were similar between groups, except for age: CL group median 83.5 years old (range, 80–92 years old) and hand-assisted laparoscopy (HALS) group median 81.5 years old (range, 80–88 years old) (P=0.027). Pre-operative cardiac and lung function risk, performance status, and pathological classification stage (pStage) were almost similar between groups (P=0.668, P=0.176, P>0.999, P=0.217). No significant differences were found for operation time. The HALS group resulted in less blood loss (median 204 mL in the CL group and median 68 mL in the HALS group, P=0.003), shorter postoperative hospital stay (median was 18 days in the CL group and median was 12 days in the HALS group, P<0.001), and fewer postoperative wound infections (18 cases in the CL group and 2 cases in the HALS group, P=0.034). Five-year relapse-free survival (5Y-RFS) was 48.1% in the CL group and 73.3% in the HALS group (P=0.028). Five-year overall survival (5Y-OS) was 48.2% in the CL group and 73.3% in the HALS group (P=0.027).ConclusionsApproximately 70% of surgical treatment for patients over 80 years old with colorectal carcinoma were performed by CL. However, HALS had significant advantages including less blood loss, fewer wound infections, and shorter hospital stays. Therefore, HALS could proactively be considered to older adult patients with colorectal cancer.     

A tumor metastasis‐associated molecule TWIST1 is a favorable target for cancer immunotherapy due to its immunogenicity

Although neoantigens are one of the most favorable targets in cancer immunotherapy, it is less versatile and costly to apply neoantigen‐derived cancer vaccines to patients due to individual variation. It is, therefore, important to find highly immunogenic antigens between tumor‐specific or associated antigens that are shared among patients. Considering the cancer immunoediting theory, immunogenic tumor cells cannot survive in the early phase of tumor progression including two processes: elimination and equilibrium. We hypothesized that highly immunogenic molecules are allowed to be expressed in tumor cells after an immune suppressive tumor microenvironment was established, if these molecules contribute to tumor survival. In the current study, we focused on TWIST1 as a candidate for highly immunogenic antigens because it is upregulated in tumor cells under hypoxia and promotes tumor metastasis, which is observed in the late phase of tumor progression. We demonstrated that TWIST1 had an immunogenic peptide sequence TWIST1_140–162, which effectively activated TWIST1‐specific CD4⁺ T‐cells. In a short‐term culture system, we detected more TWIST1‐specific responses in breast cancer patients compared with in healthy donors. Vaccination with the TWIST1 peptide also showed efficient expansion of TWIST1‐reactive HTLs in humanized mice. These findings indicate that TWIST1 is a highly immunogenic shared antigen and a favorable target for cancer immunotherapy.     

Dual Effects of Liquiritigenin on the Proliferation of Bone Cells: Promotion of Osteoblast Differentiation and Inhibition of Osteoclast Differentiation

Bone is constantly controlled by a balance between osteoblastic bone formation and osteoclastic bone resorption. Liquiritigenin is a plant‐derived flavonoid and has various pharmacological effects, such as antioxidative, antitumor, and antiinflammatory effects. Here, we show that liquiritigenin has dual effects on the proliferation of bone cells, regarding the promotion of osteoblast differentiation and the inhibition of osteoclast differentiation. Liquiritigenin‐treated murine osteoblastic MC3T3‐E1 cells showed an increased alkaline phosphatase activity and enhanced phosphorylation of Smad1/5 compared with untreated cells. Moreover, liquiritigenin inhibited osteoclast differentiation, its bone‐resorption activity through slightly decreased the phosphorylation of extracellular signal‐regulated kinase, c‐Jun N‐terminal kinase, and inhibitor of nuclear factor kappa Bα; however, the phosphorylation of Akt and p38 slightly increased in bone marrow‐derived osteoclasts. The expression levels of the osteoclast marker proteins nuclear factor of activated T‐cell cytoplasmic‐1, Src, and cathepsin K diminished. These results suggest that liquiritigenin may be useful as a therapeutic and/or preventive agent for osteoporosis or inflammatory bone diseases. Copyright © 2015 John Wiley & Sons, Ltd.     

Chronic Pulmonary Disease Caused by Tsukamurella toyonakaense

Unidentified Mycobacterium species are sometimes detected in respiratory specimens. We identified a novel Tsukamurella species (Tsukamurella sp. TY48, RIMD 2001001, CIP 111916^T), Tsukamurella toyonakaense, from a patient given a misdiagnosis of nontuberculous mycobacterial pulmonary disease caused by unidentified mycobacteria. Genomic identification of this Tsukamurella species helped clarify its clinical characteristics and epidemiology.     

The Effect of a Web-Based Cervical Cancer Survivor’s Story on Parents' Behavior and Willingness to Consider Human Papillomavirus Vaccination for Daughters: Randomized Controlled Trial

BackgroundProviding adequate information to parents who have children eligible for human papillomavirus (HPV) vaccination is essential to overcoming vaccine hesitancy in Japan, where the government recommendation has been suspended. However, prior trials assessing the effect of brief educational tools have shown only limited effects on increasing the willingness of parents to vaccinate their daughters.ObjectiveThe aim of this trial is to assess the effect of a cervical cancer survivor’s story on the willingness of parents to get HPV vaccination for their daughters.MethodsIn this double-blinded, randomized controlled trial (RCT) implemented online, we enrolled 2175 participants aged 30-59 years in March 2020 via a webpage and provided them with a questionnaire related to the following aspects: awareness regarding HPV infection and HPV vaccination, and willingness for HPV vaccination. Participants were randomly assigned (1:1) to see a short film on a cervical cancer survivor or nothing, stratified by sex (male vs female) and willingness for HPV vaccination prior to randomization (yes vs no). The primary endpoint was the rate of parents who agreed for HPV vaccination for their daughters. The secondary endpoint was the rate of parents who agreed for HPV vaccination for their daughters and the HPV vaccination rate at 3 months. The risk ratio (RR) was used to assess the interventional effect.ResultsOf 2175 participants, 1266 (58.2%) were men and 909 (41.8%) were women. A total of 191 (8.8%) participants were willing to consider HPV vaccination prior to randomization. Only 339 (15.6%) participants were aware of the benefits of HPV vaccination. In contrast, 562 (25.8%) participants were aware of the adverse events of HPV vaccination. Although only 476 (21.9%) of the respondents displayed a willingness to vaccinate their daughters for HPV, there were 7.5% more respondents in the intervention group with this willingness immediately after watching the short film (RR 1.41, 95% CI 1.20-1.66). In a subanalysis, the willingness in males to vaccinate daughters was significantly higher in the intervention group (RR 1.50, 95% CI 1.25-1.81); however, such a difference was not observed among females (RR 1.21, 95% CI 0.88-1.66). In the follow-up survey at 3 months, 1807 (83.1%) participants responded. Of these, 149 (8.2%) responded that they had had their daughters receive vaccination during the 3 months, even though we could not see the effect of the intervention: 77 (7.9%) in the intervention group and 72 (8.7%) in the control group.ConclusionsA cervical cancer survivor’s story increases immediate willingness to consider HPV vaccination, but the effect does not last for 3 months. Furthermore, this narrative approach to parents does not increase vaccination rates in children eligible for HPV vaccination.Trial RegistrationUMIN Clinical Trials Registry UMIN000039273; https://tinyurl.com/bdzjp4yf     

Evolution of thrombolytic therapy in patients with HeartWare ventricular assist device thrombosis: a single-institutional experience

Open in a separate window OBJECTIVESPump thrombosis remains a major challenge in heart failure patients with left ventricular HeartWare assist device. Current International Society for Heart and Lung Transplantation recommendations favour surgical pump exchange over lysis because safety and efficacy of lysis has been controversially reported. This study summarizes our experience on our HeartWare thrombosis prevention strategy as well as thrombolysis through implementation of our institutional standardized HeartWare assist device protocol.METHODSOutcomes of all HeartWare thrombosis patients admitted between 2010 and 2020 were analysed. Thrombolysis therapy using tissue plasminogen activator was used as the first-line therapy in this study and thrombolysis therapy efficacy was defined as freedom from stroke, bleeding, recurrent HeartWare assist device thrombosis or surgical device exchange within 30 days after lysis application.RESULTSA total of 507 patients have been included in this study and 66 patients (13%) collectively developed a first HeartWare-thrombosis after a median of 12 months (8–22 months) after HeartWare implantation. Forty patients were treated with unstandardized lysis, of whom 7 patients had thrombolysis associated complications, such as incomplete thrombus resolution requiring surgical pump exchange in 4 patients, but also intracranial haemorrhage occurring in 3 patients. Three patients died in the non-protocol group. Eight device thrombosis patients were treated according to our protocol, showing no lysis-associated complication.CONCLUSIONSDespite current recommendations, preferring surgical HeartWare pump exchange in thrombosis, thrombolysis therapy for first HeartWare thrombosis can be safe and effective in a standardized protocol setting, including anticoagulation adjustment and intensified blood pressure control management.     

Single-stage repair for ascending aortic aneurysm,artery stenosis and occlusion of neck vessels caused by Takayasu arteritis

Takayasu arteritis results in a variety of vascular symptoms, and there are some cases in which progressive vascular lesions require surgical intervention. We present a case with ascending aortic aneurysm, right common carotid artery stenosis, left common carotid artery occlusion and left subclavian artery stenosis caused by Takayasu arteritis that was successfully treated with total arch replacement and ascending aorta to right internal carotid artery bypass.