Performance of the EuroSCORE II and the Society of Thoracic Surgeons Score in patients undergoing aortic valve replacement for aortic stenosis.

Aim. The aim of this study was to evaluate the performance of the new European System for Cardiac Operative Risk Evaluation (EuroSCORE) II and the Society of Thoracic Surgeons (STS) score in patients undergoing aortic valve replacement (AVR) for aortic stenosis (AS). This study also evaluated the performance of the EuroSCORE II in high-risk patients. Methods. Three hundred and six consecutive adult patients underwent AVR with or without coronary artery bypass grafting at our institution from August 2002 to June 2012. The cut-off value of 6% for the EuroSCORE II and 10% for the STS score was used to identify high-risk in this study. Results. Operative mortality was 3.5% (N.=11). The mean expected mortality for all patients was 3.1% (O/E ratio=1.12) for the EuroSCORE II and 5.1% (O/E ratio=0.68) for the STS score. Observed versus expected mortality for the high-risk patients was 17.2% versus 11.9% (O/E ratio=1.44) for the EuroSCORE II (N.=29) and 19.3% versus 18.5% (O/E ratio=1.04) for the STS score (N.=31), and that for the low-risk was 2.1% versus 2.2% (O/E ratio=0.95) for the EuroSCORE II and 1.8% versus 3.5% (O/E ratio=0.51) for the STS score. Discrimination power of the STS score was good (area under the receiver operating characteristics curve [AUC] 0.74), but that of the EuroSCORE II was suboptimal (AUC 0.66). Conclusion. Good calibration ability of the EuroSCORE II for low-risk patients and that of the STS score for high-risk are observed. However, the EuroSCORE II underestimates the operative mortality in high-risk patients and the STS score overestimates the risk in low-risk patients.

Pro-angiogenic cytokines for prediction of outcomes in patients with advanced hepatocellular carcinoma.

BACKGROUND: We previously reported that expressions of the pro-angiogenic cytokines angiopoietin-2 (Ang-2), follistatin, granulocyte colony-stimulating factor, hepatocyte growth factor, leptin, platelet-derived growth factor-BB, platelet endothelial cell adhesion molecule-1, and vascular endothelial growth factor were associated with the response to sorafenib in patients with advanced hepatocellular carcinoma (HCC). The aim of the present study is to examine the same relationship in a larger cohort. METHODS: In the current retrospective cohort study, we measured serum levels of the eight cytokines in 120 consecutive HCC patients who were treated with sorafenib. We evaluated the effects of increased expression of serum cytokines on progression-free survival (PFS) and overall survival (OS). RESULTS: Elevated expression of Ang-2 correlated both with significantly shorter PFS (hazard ratio (HR), 1.84; 95% confidence interval (CI), 1.21-2.81), and OS (HR, 1.95; 95% CI, 1.21-3.17). Patients with more than three cytokines expressed above the median similarly had significantly shorter PFS (HR, 1.98; 95% CI, 1.30-3.06) and OS (HR, 1.94; 95% CI, 1.19-3.22). Differences in OS were evident in cases with the evidence of macroscopic vascular invasion or extrahepatic metastasis. CONCLUSION: High expression of Ang-2 or more than cytokines in serum is associated with poor PFS and OS in HCC patients treated with sorafenib.

Effect of hepatic arterial infusion chemotherapy of 5-fluorouracil and cisplatin for advanced hepatocellular carcinoma in the Nationwide Survey of Primary Liver Cancer in Japan.

BACKGROUND: The efficacy of hepatic arterial infusion chemotherapy for the treatment of advanced hepatocellular carcinoma (HCC) remains unclear. METHODS: The outcome of 476 patients with HCC who underwent hepatic arterial infusion chemotherapy with 5-fluorouracil and cisplatin (HAIC) were compared with 1466 patients who did not receive active therapy. RESULTS: A survival benefit of the therapy after adjusting for known risk factors was observed (hazard ratio, 0.48; 95% CI, 0.41-0.56; P<0.0001). In propensity score-matched analysis (n=682), median survival time was longer for patients who underwent chemotherapy (14.0 months) than for patients who did not receive active treatment (5.2 months, P<0.0001). CONCLUSION: For advanced HCC, HAIC is considered to be an effective treatment.

Isolation and characterization of a novel short peptide associated with Crohn's disease.

Phage display technology has been utilized to select target molecules against circulating antibodies. The aims of this study were to isolate a peptide that binds with serum from Crohn's disease (CD) patients and to examine its diagnostic and pathogenic significance. A phage display library was constructed using cDNA from Caco-2 cells. Affinity selection using this cDNA library and serum samples from patients with CD was then performed. Phage clones that specifically reacted with the CD sera were then selected using a phage enzyme-linked immunosorbent assay (ELISA). After the DNA sequences of the selected phages were determined and converted to amino acid sequences, the synthesized peptides were examined using an ELISA. The effect of the synthesized peptides on cytokine release from cultured blood mononuclear cells was investigated. An ELISA analysis for TCP-353 demonstrated that while 61·7% of the samples from CD patients were seroreactive, seroreactivity was less common among patients with ulcerative colitis (7·3%), acute colitis (0%) or colon cancer (11·4%) and among normal subjects (2·8%). The induction of interleukin (IL)-1ß, IL-6 and tumour necrosis factor (TNF)-α release, but not IL-10 release, in response to TCP-353 peptide was enhanced in CD mononuclear cells only. We isolated a novel peptide that specifically binds to CD sera and stimulates the proinflammatory responses of CD mononuclear cells. TCP-353 may have diagnostic, pathogenic and therapeutic significance with regard to the treatment of CD.

Evolution of prognostic factors in hepatocellular carcinoma in Japan.

BACKGROUND: The surveillance of hepatocellular carcinoma (HCC) has become prevalent, and the modalities for its treatment have improved. AIM: To understand the changes that occur in the characteristics and prognostic factors of HCC with time. METHODS: Newly diagnosed HCC patients were divided into two groups; patients treated before 31 December 2000 (n = 504), and after 1 January 2001 (n = 746), and their clinical backgrounds and prognostic factors were analysed. RESULTS: The number of patients negative for both Hepatitis B surface antigen (HBsAg) and Hepatitis C virus antibody (HCVAb) increased with time (NBNC-HCC). The size of HCC decreased in patients who were positive for HBsAg (B-HCC) or HCVAb (C-HCC), whereas no difference was observed in NBNC-HCC. The patient survival of C-HCC improved; however, no difference was detected for NBNC-HCC. In multivariate analysis, low albumin, high aspartate aminotransferase (AST), ascites, large tumour size, multiple tumour number and high alpha-fetoprotein were risk factors for survival before 2000, whereas the presence of HBsAg was additionally selected as a good prognostic factor and AST was excluded after 2001. CONCLUSIONS: The prognostic factors as well as clinical background of HCC changed with time, and the presence of HBsAg was found to be an additional good prognostic factor after 2001.

[Infective endocarditis with acute embolism to the lower extremity artery caused by a vegetation: report of a case].

Successful surgical treatment of a case of infective endocarditis with embolism to a lower extremity artery is reported. A 71-year-old man was referred to our hospital for the treatment of infective endocarditis. Echocardiography showed a vegetation on the non-coronary cusp of the aortic valve measuring 19 mm in diameter. We planned surgical treatment, including aortic valve replacement, however, embolism of a lower extremity artery by the vegetation occurred during the waiting period for the operation. We removed the offending vegetation from the popliteal artery and replaced the peccant aortic valve with a prosthetic valve in separate operations. The postoperative course was uneventful and the patient was transferred to another hospital on the 33rd day after the valve replacement surgery.

Clinical trial: comparison of alendronate and alfacalcidol in glucocorticoid-associated osteoporosis in patients with ulcerative colitis.

BACKGROUND: Bone loss is often observed in patients with ulcerative colitis, particularly if they require glucocorticoids. AIM: To determine whether the bisphosphonate, alendronate, is safe and effective in preserving bone mass compared to the active vitamin D3, alfacalcidol, in ulcerative colitis patients receiving glucocorticoids. METHODS: Thirty-nine patients with ulcerative colitis and treated with glucocorticoids were randomized to receive alendronate (5 mg/day) or alfacalcidol (1 microg/day) daily for 12 months. Loss of bone mass was evaluated by bone mineral density, bone resorption by urinary N-telopeptide for type I collagen, and bone formation by serum bone alkaline phosphatase. RESULTS: Alendronate, but not alfacalcidol, significantly increased bone mineral density in the lumbar spine. Alendronate decreased serum bone alkaline phosphatase levels, but alfacalcidol did not. Urinary N-telopeptide for type I collagen levels decreased in both groups, but were significantly lower in the alendronate group. There were no significant differences in the adverse events in the two groups. CONCLUSION: Our study indicates that alendronate is a safe, well-tolerated and more effective therapy than alfacalcidol for preventing glucocorticoid-associated bone loss in patients with ulcerative colitis.

Rejection of cardiac xenografts transplanted from alpha1,3-galactosyltransferase gene-knockout (GalT-KO) pigs to baboons.

The use of alpha1,3-galactosyltransferase gene-knockout (GalT-KO) swine donors in discordant xenotransplantation has extended the survival of cardiac xenografts in baboons following transplantation. Eight baboons received heterotopic cardiac xenografts from GalT-KO swine and were treated with a chronic immunosuppressive regimen. The pathologic features of acute humoral xenograft rejection (AHXR), acute cellular xenograft rejection (ACXR) and chronic rejection were assessed in the grafts. No hyperacute rejection developed and one graft survived up to 6 months after transplantation. However, all GalT-KO heart grafts underwent graft failure with AHXR, ACXR and/or chronic rejection. AHXR was characterized by interstitial hemorrhage and multiple thrombi in vessels of various sizes. ACXR was characterized by TUNEL(+) graft cell injury with the infiltration of T cells (including CD3 and TIA-1(+) cytotoxic T cells), CD4(+) cells, CD8(+) cells, macrophages and a small number of B and NK cells. Chronic xenograft vasculopathy, a manifestation of chronic rejection, was characterized by arterial intimal thickening with TUNEL(+) dead cells, antibody and complement deposition, and/or cytotoxic T-cell infiltration. In conclusion, despite the absence of the Gal epitope, acute and chronic antibody and cell-mediated rejection developed in grafts, maintained by chronic immunosupression, presumably due to de novo responses to non-Gal antigens.

Prognostic factors and treatment effects for hepatocellular carcinoma in Child C cirrhosis.

The aim of this study is to elucidate the prognostic factors and the treatment effect on survival in hepatocellular carcinoma (HCC) patients with Child C cirrhosis. Out of 3330 newly discovered HCC patients, 157 consecutive HCC individuals with Child C cirrhosis were enrolled. The prognostic factors were examined by Cox proportional hazards regression analysis and their survival was compared by propensity score-matched analysis. Multivariate analysis revealed that high serum bilirubin (>3 mg dl(-1)), the presence of uncontrollable ascites, and a high platelet count (>8 x 10(4) mm(-3)), so-called background liver factors, as well as multiple tumours, large tumours (>3 cm), high alpha-fetoprotein (>400 ng ml(-1)), and the presence of portal vein thrombus, so-called tumour factors, were factors of poor prognosis. While transcatheter arterial chemoembolisation (TACE) was a factor of good prognosis (relative risk=0.50, 95%CI=0.27-0.89, P=0.019), local ablation therapy and transcatheter arterial chemoinfusion (TAI) were not significant prognostic factors. The survival of patients who received TACE was superior to matched patients without active treatment (P=0.009); however, we did not observe survival benefit after local ablation therapy or TAI. These results suggested that tumour factors as well as background liver factors are prognostic factors of HCC even in patients with Child C cirrhosis, and selective use of TACE in these patients provides survival benefit.

Development of granulocyte and monocyte adsorptive apheresis in the rat dextran sodium sulfate-induced colitis model.

Granulocytapheresis (GCAP) selectively removes large numbers of granulocytes and monocytes from peripheral blood by adsorptive apheresis, and in patients with ulcerative colitis GCAP has been associated with significant efficacy. However, the mechanism(s) of efficacy of this strategy is poorly understood. This rat model of dextran sodium sulfate (DSS)-induced colitis was to investigate the effect of GCAP on tumor necrosis factor (TNF)-alpha release by peripheral leukocytes. By using mini columns, an experimental GCAP setting was developed and applied to the DSS-induced colitis model. The production of TNF-alpha by lipopolysaccharide-activated leukocytes in whole blood was measured by enzyme-linked immunosorbent assay. In rats that received GCAP with columns containing leukocytapheresis carriers, TNF-alpha release by leukocytes was significantly (p < 0.05) suppressed, while no change in TNF-alpha production was seen in rats that received GCAP with sham columns. This first experimental setting in the rat colitis model suggests that GCAP is feasible in animals and should shed light on the mechanism(s) of GCAP in clinical settings. Given that TNF-alpha is a major inflammatory cytokine, down-modulation of TNF-alpha might represent one mechanism of antiinflammatory effects of GCAP.

Effect of ruminal administration of Escherichia coli wild type or a genetically modified strain with enhanced high nitrite reductase activity on methane emission and nitrate toxicity in nitrate-infused sheep.

The effects of two kinds of Escherichia coli (E. coli) strain, wild-type E. coli W3110 and E. coli nir-Ptac, which has enhanced NO(2) reduction activity, on oral CH(4) emission and NO(3) toxicity in NO(3)-treated sheep were assessed in a respiratory hood system in a 4 x 6 Youden square design. NO(3) (1.3 g NaNO(3)/kg(0.75) body weight) and/or E. coli strains were delivered into the rumen through a fistula as a single dose 30 min after the morning meal. Escherichia coli cells were inoculated for sheep to provide an initial E. coli cell density of optical density at 660 nm of 2, which corresponded to 2 x 10(10) cells/ml. The six treatments consisted of saline, E. coli W3110, E. coli nir-Ptac, NO(3), NO(3) plus E. coli W3110, and NO(3) plus E. coli nir-Ptac. CH(4) emission from sheep was reduced by the inoculation of E. coli W3110 or E. coli nir-Ptac by 6 % and 12 %, respectively. NO(3) markedly inhibited CH(4) emission from sheep. Compared with sheep given NO(3) alone, the inoculation of E. coli W3110 to NO(3)-infused sheep lessened ruminal and plasma toxic NO(2) accumulation and blood methaemoglobin production, while keeping ruminal methanogenesis low. Ruminal and plasma toxic NO(2) accumulation and blood methaemoglobin production in sheep were unaffected by the inoculation of E. coli nir-Ptac. These results suggest that ruminal methanogenesis may be reduced by the inoculation of E. coli W3110 or E. coli nir-Ptac. The inoculation of E. coli W3110 may abate NO(3) toxicity when NO(3) is used to inhibit CH(4) emission from ruminants.

Potential of aspirin to inhibit thrombotic microangiopathy in alpha1,3-galactosyltransferase gene-knockout pig hearts after transplantation in baboons.

Hearts from alpha1,3-Galactosyltransferase gene-knockout (GaIT-KO) pigs were transplanted heterotopically into 8 baboons that received an anti-CD154 monoclonal antibody (mAb)-based immunosuppressive regimen and heparin. Three baboons died or were euthanized with beating grafts on 16, 23, and 56 days, respectively, and the remaining 5 grafts functioned for 59-179 days. Hyperacute rejection did not occur, and classical features of acute humoral xenograft or acute cellular rejection were rare. However, thrombotic microangiopathy (TM) developed in all cases; its onset was delayed in 2 baboons that received aspirin. Function of a pig organ in a baboon for a period approaching 6 months has not been reported previously and lends encouragement that the barriers to xenotransplantation will be overcome, but TM requires investigation.

Troponin T levels in baboons with pig heterotopic heart transplants.

Troponin T levels have been monitored in baboons (n = 8) undergoing pig heterotopic heart transplantation, and correlated with a decrease in graft contractions and graft survival. Pig heart graft survival was from 12 to 139 days (mean 45, median 33), and graft failure was associated with predominant thrombotic microangiopathy and ischemia, with focal hemorrhage, and edema. An increase in troponin T levels 5 to 6 days before graft failure correlated closely with diminished graft contractions. An increase in troponin T was a reliable indicator that graft dysfunction was occurring.

Bone marrow transplantation from alpha1,3-galactosyltransferase gene-knockout pigs in baboons.

BACKGROUND: Successful hematopoietic cell allotransplantation results in donor-specific tolerance, but this approach has been unsuccessful in the wild-type pig-to-baboon xenotransplantation model, as pig cells were lost from the circulation within 5 days. However, after cessation of immunosuppressive therapy on day 28, all baboons demonstrated non-specific unresponsiveness on mixed leukocyte reaction (MLR) for at least 30 days. We have now investigated the transplantation of bone marrow (BM) cells from miniature swine homozygous for alpha1,3-galactosyltransferase gene-knockout (GalT-KO). METHODS: Baboons (n = 3) were pre-treated with whole body and thymic irradiation, anti-thymocyte globulin, and splenectomy, and received immunosuppressive and supportive therapy for 28 days. BM was harvested from GalT-KO swine (n = 3). The baboons were monitored for the presence of pig cells by flow cytometry and colony-forming units (CFUs), and for cellular reactivity by MLR. RESULTS: A mean of 11 x 10(8) BM cells/kg was infused into each baboon. The mean absolute numbers and percentages of pig cells detected in the blood at 2 h and on days 1, 2 and 4, respectively, were 641/microl (9.5%), 132/microl (3.4%), 242/microl (3.9%), and 156/microl (2.9%). One baboon died (from accidental hemorrhage) on day 6, at which time chimerism was present in the blood (2.0%) and BM (6.4%); pig cell engraftment in the BM was confirmed by polymerase chain reaction (PCR) of CFUs. In the two other baboons, blood chimerism was lost after day 5 but returned at low levels (<1%) between days 9 to 16 and 7 to 17, respectively, indicating transient BM engraftment. Both surviving baboons showed non-specific unresponsiveness on MLR until they were euthanized on days 85 and 110, respectively. CONCLUSIONS: By using BM cells from GalT-KO pigs, chimerism was detected at levels comparable with previous studies when 30-fold more growth factor-mobilized peripheral blood progenitor cells had been transplanted. In addition, cellular hyporesponsiveness was prolonged. However, long-term engraftment and chimerism were not achieved.

Reduction of anti-Galalpha1,3Gal antibodies by infusion of types 2 and 6 gal trisaccharides conjugated to poly-L-lysine.

To investigate the specificity of anti-Galalpha1,3Gal (Gal) antibodies (Abs) with respect to Gal oligosaccharides of types 2 and 6, eight baboons received an intravenous infusion of either a poly-l-lysine conjugate of Gal type 2 (n = 5) or type 6 (n = 3), followed 48 h later by the alternative Gal type 6 or 2 conjugate, respectively. IgM Abs reactive to Gal type 2 were depleted by 80 to 89% by either Gal conjugate. IgM reactive to Gal type 6 was less efficiently depleted by the Gal type 2 conjugate (57% depletion) than the Gal type 6 (82% depletion). Gal-reactive IgG was depleted more slowly and less efficiently by either glycoconjugate (initially by only 28 to 54%). Our results indicate that the Gal type 6 conjugate depletes most anti-Gal IgM, but the Gal type 2 conjugate is less efficient in depleting anti-Gal IgM reactive with type 6. There remain small fractions of antibody that are unadsorbed, particularly of IgG, probably due to their low affinity and distribution in both the intra- and extra-vascular compartments.

Absence of humoral and cellular alloreactivity in baboons sensitized to pig antigens.

AIM: to study whether sensitization to pig antigens results in humoral and/or cellular sensitization to alloantigens in baboons, and thus increases the risks of organ allotransplantation after xenotransplantation. Serum from baboons that were naive (n = 4), sensitized to Gal alpha 1,3Gal (Gal) antigens (n = 2), or sensitized to Gal + non-Gal pig antigens (n = 2) were tested by flow cytometry for the presence of immunoglobulin G (IgG) and IgM antibodies that bind to pig or baboon peripheral blood mononuclear cells (PBMC). Two allosensitized baboons were used as positive controls. The same 10 sera were tested in a complement-mediated cytotoxicity assay to detect cytotoxic antibodies against pig, allo and self-PBMC. The T-cell responses of the same baboons to allogeneic and pig PBMC stimulators in mixed lymphocyte reaction (MLR) were studied. All baboon sera contained cytotoxic antibodies that bound to pig PBMC. Binding and cytotoxicity were higher in xenosensitized baboons, particularly in those sensitized to Gal + non-Gal antigens (P < 0.001). None of the naive or xenosensitized baboon sera bound to baboon PBMC. Serum from allosensitized baboons showed anti-baboon IgG and IgM binding, but there was no increase in binding to pig PBMC or in cytotoxicity to pig cells. The MLR response to pig stimulators in baboons sensitized to non-Gal pig antigens was greater than that of naive or Gal-sensitized baboons (P < 0.001), but there was no increase in the response to baboon cells. In baboons, no in vitro evidence that a previous pig xenograft might endanger the outcome of a subsequent allograft was documented.

Endoventricular circular patch plasty for end-stage valvular cardiomyopathy.

We present here a case of end-stage non-ischemic valvular dilated cardiomyopathy (DCM) associated with mitral regurgitation (MR). The patient underwent surgery where left ventricular volume reduction using endoventricular circular patch plasty (EVCPP) and mitral valve replacement (MVR) were performed. He has improved much after the operation and is now in New York Heart Association (NYHA) functional class II.

Tricuspid valve surgery for functional tricuspid valve regurgitation associated with left-sided valvular disease.

OBJECTIVES: We have reviewed 260 patients who underwent initial tricuspid valve surgery for functional tricuspid valve regurgitation (TR) and analyzed independent predictors for early and late unfavorable results. MATERIALS AND METHODS: Between 1981 and 1998, 260 tricuspid valve operations were performed for functional TR. There were 94 males and 166 females with a mean age of 55 years. The tricuspid valve surgery procedures consisted of De Vega tricuspid annuloplasty in 240 patients, ring annuloplasty in four patients, and tricuspid valve replacement in 16 patients. The mean duration of follow-up was 7.8 years. RESULTS: Hospital mortality was 8.9% (23 patients). Late deaths occurred in 34 patients including cardiac-related late deaths in 26 patients. The survival rates were 83+/-2% at 5 years and 78+/-3% at 10 years. Late tricuspid valve reoperation was performed on 13 patients due to residual or recurrent TR in 12 patients and thrombosed tricuspid bileaflet mechanical valve in one patient. The tricuspid valve reoperation-free survival rate was 90+/-2% at 5 years and 84+/-3% at 10 years. The only predictor of hospital mortality was preoperative highly elevated right atrial pressure (P=0.01). Variables predictive of cardiac-related late death were preoperative New York Heart Association (NYHA) class IV (P=0.01) and poor left ventricular ejection fraction (LVEF) (P=0.02). Residual TR of more than grade 2+ early after tricuspid annuloplasty was a significant risk factor for late tricuspid valve reoperation (P=0.01). Preoperative TR of grade 4+ was predictive of early residual TR (P=0.04). CONCLUSIONS: Tricuspid valve surgery for functional TR can be performed with acceptable levels of early mortality. Cardiac-related late mortality after tricuspid surgery may be improved by earlier surgical treatment before NYHA class IV or deterioration of LVEF occurs. To prevent late tricuspid reoperation, it is important not to leave residual TR of grade 2+ or more after tricuspid annuloplasty.