Indocyanine green (TCG) clearance as a monitor to evaluate right heart function

Systemic venous return to the heart is disturbed as a result of right heart failure. ICG clearance is known to be influenced by hepatic venous return to the right atrium. Under a hypothesis that right heart function could be evaluated by ICG clearance test, patients with mitral valve disease (Group M, n = 29), aortic valve disease (Group A, n = 16), ischemic heart disease (Group CABG, n = 19) were studied. Preoperative K-ICG (normal range > 0.17) in the Group M was significantly lower than those in the Group A and Group CABG (0.097 +/- 0.037 vs 0.166 +/- 0.032 and 0.171 +/- 0.027, p < 0.05). In the Group M, patients who underwent tricuspid annuloplasty (TAP) had significantly lower K-ICG than the others (0.077 +/- 0.026 vs 0.113 +/- 0.038, p < 0.05). Postoperatively, K-ICG of TAP patients significantly increased (0.092 +/- 0.031, p < 0.05) when compared to their preoperative value. ICG clearance test was useful to quantify the right heart function, especially in the postoperative evaluation.     

Pathological findings of multifocal choroiditis with panuveitis and punctate inner choroidopathy

PURPOSE: To compare the pathological findings between multifocal choroiditis with panuveitis (MCP) and punctate inner choroidopathy (PIC). METHODS: Fourteen eyes of 14 patients clinically diagnosed as having MCP or PIC who underwent surgical excision of choroidal neovascularization (CNV) were studied. Immunohistochemical findings of the excised CNV in MCP (eight eyes) and PIC (six eyes) cases were compared. Antibodies against vascular endothelial growth factor (VEGF), CD68, CD3, and CD20 were used as primary antibodies. RESULTS: Expression of VEGF and CD68 in the CNV was observed in all MCF and PIC cases. In three of eight eyes with MCP, intraocular inflammatory findings were found clinically, while immunohistochemical study demonstrated infiltration of CD20-positive B lymphocytes in the CNV. No B lymphocyte infiltration was found in the six eyes with PIC. No differences in pathological findings were found between the five MCP eyes without intraocular inflammation and the six PIC eyes, with all eyes showing no B lymphocyte infiltration. CONCLUSIONS: In MPC cases showing clinical inflammatory findings, infiltration of B lymphocytes was also observed histopathologically, suggesting that the presence of inflammatory cells in the anterior chamber or vitreous body clinically is an indicator of active inflammatory CNV. However, this study clarifies that MCP eyes without intraocular inflammation and PIC eyes are not different in histopathological findings.     

Metabolism of 2- and 3-tert-butyl-4-hydroxyanisole (2- and 3-BHA) in the rat. (II): Metabolism in forestomach and covalent binding to tissue macromolecules

The mechanism of action of 2(3)-tert-butyl-4-hydroxyanisole (2-BHA or 3-BHA) on rat forestomach epithelium was studied by examining the metabolites of BHA in the stomach and the covalent binding of BHA to macromolecules in the forestomach epithelium. Male F344 rats 6 weeks old were given a single intragastric injection of 1 g/kg body wt of [tert-14C]-3-BHA (Bu-3-BHA) or [methyl-14C]-3-BHA (Me-3-BHA), and 6 h later BHA metabolites in the forestomach, glandular stomach and stomach contents were examined by thin-layer chromatography. No significant amounts of metabolites were detected in the forestomach or glandular stomach epithelium and almost all the radioactivity in these tissues was extracted with organic solvents. In in vitro experiments also, no significant amounts of metabolites were detected when the 9000 g supernatant of the forestomach or glandular stomach epithelium, or gastric juice was incubated with Bu-3-BHA in the absence or presence of NADPH. In binding studies, rats were given Bu-3-BHA, [tert-14C]-2-BHA (Bu-2-BHA), Me-3-BHA or [methyl-14C] butylated hydroxytoluene (Me-BHT) intragastrically at a dose of 1 g/kg body wt with or without pretreatment with unlabelled 1% 3-BHA or BHT in the diet for 6 days. Six hours after treatment with a labelled compound, the rats were sacrificed and the DNA, RNA and protein of their forestomach, glandular stomach, liver and kidney were isolated. Bu-3-BHA, Bu-2-BHA and Me-3-BHA did not bind covalently to forestomach DNA or RNA, and the amounts of radioactivity of these compounds bound to proteins in the 4 tissues were similar. These findings suggest that BHA acts on the forestomach epithelium directly without metabolic activation, and that its action is not related to its binding to DNA or RNA.     

Arachidonate-enriched triglyceride oil does not promote tumor development in a rat medium-term multi-organ carcinogenesis model

The modifying potential on tumor development of arachidonate-enriched triglyceride oil (ARA-oil) containing approximately 40% arachidonic acid was investigated in a medium-term multi-organ carcinogenesis bioassay using male and female F344 rats. The animals were sequentially given five carcinogens with different target sites in the first 4 weeks, and then administered ARA-oil for 24 weeks at dietary levels of 0% (control), 1.25%, 2.5% or 5.0%. No statistically significant differences in incidences and multiplicities of hyperplastic and neoplastic lesions were showed in the large intestine in either sex. In the liver, kidney, and lung in both sexes, and the mammary gland and uterus in females, tumor promoting potential was not evident with ARA-oil treatment. ARA-oil did not affect the quantitative data for glutathione S-transferase placental form positive foci of the liver. Increased induction of hyperplastic or neoplastic lesions in the urinary bladder and thyroid in ARA-oil-treated groups was without dose dependence. In addition, a second experiment with ARA-oil only administration for 8-week revealed no effects on cellular proliferation in the urinary bladder or thyroid in either sex. These results indicate that ARA-oil has no tumor promoting potential in any organs or tissues initiated with the five carcinogens applied in the present study.     

Adding collagen to adipose tissue transplant increases engraftment by promoting cell proliferation,neovascularisation and macrophage activity in a rat model

To clarify the effect of collagen addition to transplanted adipose tissue on angiogenesis, cell proliferation and tissue remodelling process and reveal whether collagen addition contributes to improving transplanted adipose tissue engraftment in rats. Adipose tissue was harvested from the inguinal and injected into the back of the rat, in addition to collagen. Engraftment tissue was harvested, semi‐quantitatively evaluated and underwent haematoxylin and eosin or Perilipin staining. Moreover, we evaluated viable adipocyte counts and neovascularisation. Macrophages were evaluated using flow cytometry, and the adiponectin or vascular endothelial growth factor (VEGF) mRNA was detected using real‐time polymerase chain reaction. By collagen addition to transplanted adipose tissue, higher engraftment rate semi‐quantitatively and a greater number of new blood vessels histologically were identified. Perilipin staining revealed a higher adipocyte number. The total cell, M1 macrophage and M2 macrophage count were higher. There was increased adiponectin mRNA significantly at week 4 compared to that at week 1 after transplantation. Note that the expression levels of VEGF mRNA increased. In rats, adding collagen enhanced cell proliferation, induced M2 macrophages, which are involved in wound healing, and promoted adipocytes and neovascularisation. Therefore, collagen addition to transplanted adipose tissue could increase the engraftment rate of adipose tissue.     

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.     

Lack of a modifying effect by the diuretic drug furosemide on the development of neoplastic lesions in rat two-stage urinary bladder carcinogenesis

The effect of the diuretic drug furosemide on two-stage urinary bladder carcinogenesis in F344 rats initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was investigated with regard to possible promoting activity. BBN was administered at 2 doses, 0.01 or 0.05%, in drinking water for 4 wk, and thereafter furosemide was given by gavage 3 times weekly for 32 wk, 250 mg/kg body weight. Furosemide ingestion induced diuresis with an alkaline, hypotonic urine. No significant difference with regard to incidences of bladder lesions were apparent between furosemide and control groups. The present investigation indicated that neither furosemide nor its related polyuria acted as a promoter in two-stage urinary bladder carcinogenesis.     

Effects of tranexamic acid on coagulofibrinolytic markers during the early stage of severe trauma: A propensity score–matched analysis

Tranexamic acid (TXA) reduces the risk of bleeding trauma death without altering the need for blood transfusion. We examined the effects of TXA on coagulation and fibrinolysis dynamics and the volume of transfusion during the early stage of trauma. This subanalysis of a prospective multicenter study of severe trauma included 276 patients divided into propensity score–matched groups with and without TXA administration. The effects of TXA on coagulation and fibrinolysis markers immediately at (time point 0) and 3 hours after (time point 3) arrival at the emergency department were investigated. The transfusion volume was determined at 24 hours after admission. TXA was administered to the patients within 3 hours (median, 64 minutes) after injury. Significant reductions in fibrin/fibrinogen degradation products and D-dimer levels from time points 0 to 3 in the TXA group compared with the non-TXA group were confirmed, with no marked differences noted in the 24-hour transfusion volumes between the 2 groups. Continuously increased levels of soluble fibrin, a marker of thrombin generation, from time points 0 to 3 and high levels of plasminogen activator inhibitor-1, a marker of inhibition of fibrinolysis, at time point 3 were observed in both groups. TXA inhibited fibrin(ogen)olysis during the early stage of severe trauma, although this was not associated with a reduction in the transfusion volume. Other confounders affecting the dynamics of fibrinolysis and transfusion requirement need to be clarified.     

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.