ABO incompatibility is no longer considered a contraindication for adult living donor liver transplantation (ALDLT) due to various strategies to overcome the ABO blood group barrier. We report the ...largest single‐center experience of ABO‐incompatible (ABOi) ALDLT in 235 adult patients. The desensitization protocol included a single dose of rituximab and total plasma exchange. In addition, local graft infusion therapy, cyclophosphamide, or splenectomy was used for a certain time period, but these treatments were eventually discontinued due to adverse events. There were three cases (1.3%) of in‐hospital mortality. The cumulative 3‐year graft and patient survival rates were 89.2% and 92.3%, respectively, and were comparable to those of the ABO‐compatible group (n = 1301). Despite promising survival outcomes, 17 patients (7.2%) experienced antibody‐mediated rejection that manifested as diffuse intrahepatic biliary stricture; six cases required retransplantation, and three patients died. ABOi ALDLT is a feasible method for expanding a living liver donor pool, but the efficacy of the desensitization protocol in targeting B cell immunity should be optimized.
This article presents the clinical results of ABO‐incompatible adult living donor liver transplantation in a single institution.
Near infrared spectroscopy (NIRS) is a non-invasive method to measure brain activity via changes in the degree of hemoglobin oxygenation through the intact skull. As optically measured hemoglobin ...signals strongly correlate with BOLD signals, simultaneous measurement using NIRS and fMRI promises a significant mutual enhancement of temporal and spatial resolutions. Although there exists a powerful statistical parametric mapping tool in fMRI, current public domain statistical tools for NIRS have several limitations related to the quantitative analysis of simultaneous recording studies with fMRI. In this paper, a new public domain statistical toolbox known as NIRS-SPM is described. It enables the quantitative analysis of NIRS signal. More specifically, NIRS data are statistically analyzed based on the general linear model (GLM) and Sun's tube formula. The
p-values are calculated as the excursion probability of an
inhomogeneous random field on a representation manifold that is dependent on the structure of the error covariance matrix and the interpolating kernels. NIRS-SPM not only enables the calculation of activation maps of oxy-, deoxy-hemoglobin and total hemoglobin, but also allows for the super-resolution localization, which is not possible using conventional analysis tools. Extensive experimental results using finger tapping and memory tasks confirm the viability of the proposed method.
Over the past two decades, the age of liver transplantation (LT) recipients has been increasing. We reviewed our experience with LT for patients aged ≥70 years (range: 70–78 years) and investigated ...the feasibility of performing LT, especially living donor LT (LDLT), for older patients. We retrospectively reviewed the medical records of 25 patients (15 LDLT recipients, 10 deceased donor LT recipients) aged ≥70 years who underwent LT from January 2000 to April 2016. Their perioperative morbidity rate was 28.0%, and the in‐hospital mortality rate was 16.0%; these results were comparable to those of matched patients in their 60s (n = 73; morbidity, p = 0.726; mortality, p = 0.816). For patients in their 70s, the 1‐ and 5‐year patient survival rates were 84.0% and 69.8%, and the 1‐ and 5‐year graft survival rates were 83.5% and 75.1%, respectively. Comparisons of patient and graft survival rates between matched patients in their 60s and 70s showed no statistically significant differences (patient survival, p = 0.372; graft survival, p = 0.183). Our experience suggests that patients aged ≥70 years should not be excluded from LT, or even LDLT, based solely on age and implies that careful selection of recipients and donors as well as meticulous surgical technique are necessary for successful results.
Patients aged 70 years or older should not be excluded from undergoing liver transplant or even living donor liver transplant based solely on chronological age.
ABO‐incompatible (ABOi) dual‐graft (DG) adult living donor liver transplantation (ALDLT) is not commonly performed due to its inherently intricate surgical technique and immunological complexity. ...Therefore, data are lacking on the short‐ and long‐term clinical outcomes of ABOi DG ALDLT. We performed a retrospective study by reviewing the medical records of patients who underwent ABOi DG ALDLT between 2008 and 2014. Additionally, computed tomography volumetric analysis was conducted to assess the graft regeneration rate. The mean age of a total of 28 recipients was 50.2 ± 8.5 years, and the mean model for end‐stage liver disease score was 12.2 ± 4.6. The 1‐, 3‐, and 5‐year patient survival rate was 96.4% during the mean follow‐up period of 57.0 ± 22.4 months. The 1‐, 3‐, and 5‐year graft survival rate was 96.4%, 94.2%, and 92.0%, respectively, and no significant differences were observed between ABO‐compatible (ABOc) and ABOi grafts (P = .145). The biliary complication rate showed no significant difference (P = .195) between ABOc and ABOi grafts. Regeneration rates of ABOi grafts were not significantly different from those of ABOc grafts. DG ALDLT with ABOi and ABOc graft combination seems to be a feasible option for expanding the donor pool without additional donor risks.
Dual‐graft adult living donor liver transplantation with ABO‐incompatible grafts demonstrates an acceptable outcome in patient and graft survival, and proves to be safe in regards to biliary complications associated with the ABO incompatibility, which suggests its feasibility to expand the living liver donor pool without increasing donor risks.
Objective. To analyse factors associated with endocervical cone margin involvement and suggest appropriate cone depth for the conization procedure. Design. Retrospective cohort study. Setting. ...Gynecological oncology center. Population. One thousand two hundred and twenty women undergoing conization for cervical intraepithelial neoplasia (CIN) II or III or stage IA1 microinvasive cervical carcinoma. Methods. The following factors were analysed: age, parity, gravida, conization type, margin status, disease severity and specimen depth. Receiver operating characteristic curve analyses were used to determine the best cut‐off points to define appropriate cone depth. Main outcome measures. Cone depth to avoid endecervical margin involvement. Results. Ninety‐one women had endocervical margin involvement (7.5%). This was positively associated with disease severity and age and inversely related to cone depth. In women under 50 years of age, the cut‐off value was achieved at 1.8 cm cone depth, with high sensitivity and relatively low specificity area under the curve (AUC) 0.64, sensitivity 0.86, specificity 0.27, p= 0.005. For a subset of CIN II patients aged ≤50 years, the cut‐off value was 1.2 cm (AUC 0.75, sensitivity 0.90, specificity 0.47, p= 0.008). In women <40 years of age, the cut‐off value was 1.8 cm (AUC 0.60, sensitivity 0.88, specificity 0.25, p= 0.036). In a subset of CIN II, the cut‐off value was 0.9 cm (AUC 0.87, sensitivity 0.83, specificity 0.69, p= 0.002). Conclusions. Age, disease severity and cone depth are predictive factors for endocervical margin involvement. In women of reproductive age, the appropriate cone depth to avoid endocervical margin involvement can be changed depending on age and disease severity.
The present study aimed to investigate the difference in major adverse cardiac events (MACE) at 12 months in patients with coronary bifurcation lesions after double kissing double crush (DK crush) or ...provisional stenting (PS) techniques.
Provisional side branch (SB) stenting is preferable to DK crush because it has been associated with fewer complications. It is unknown which strategy would provide the best results.
From April 2007 to June 2009, 370 unselected patients with coronary bifurcation lesions from 7 Asian centers were randomly assigned to either the DK or the PS group. Additional SB stenting in PS was required if final results were suboptimal. The primary end point was the occurrence of MACE at 12 months, including cardiac death, myocardial infarction, or target vessel revascularization (TVR). Secondary end point was the angiographic restenosis at 8 months.
There were 3 procedural occlusions of SB in the PS group. At 8 months, angiographic restenosis rates in the main vessel and SB were significantly different between the DK (3.8% and 4.9%) and the PS groups (9.7% and 22.2%, p = 0.036 and p < 0.001, respectively). Additional SB stenting in the PS group was required in 28.6% of lesions. TVR was 6.5% in the DK group, occurring significantly less often than in the PS group (14.6%, p = 0.017). There were nonsignificant differences in MACE and definite stent thrombosis between the DK (10.3% and 2.2%) and PS groups (17.3%, and 0.5%, p = 0.070 and p = 0.372, respectively).
DK crush was associated with a significant reduction of TLR and TVR in this unselected patient population. However, there was no significant difference in MACE between DK and the PS groups. (Randomized Study on DK Crush Technique Versus Provisional Stenting Technique for Coronary Artery Bifurcation Lesions; ChicTR-TRC-00000015).
The study aimed to investigate the difference in major adverse cardiac event (MACE) at 1-year after double kissing (DK) crush versus Culotte stenting for unprotected left main coronary artery ...(UPLMCA) distal bifurcation lesions.
DK crush and Culotte stenting were reported to be effective for treatment of coronary bifurcation lesions. However, their comparative performance in UPLMCA bifurcation lesions is not known.
A total of 419 patients with UPLMCA bifurcation lesions were randomly assigned to DK (n = 210) or Culotte (n = 209) treatment. The primary endpoint was the occurrence of a MACE at 1 year, including cardiac death, myocardial infarction, and target vessel revascularization (TVR). In-stent restenosis (ISR) at 8 months was secondary endpoint, and stent thrombosis (ST) served as a safety endpoint. Patients were stratified by SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) and NERS (New Risk Stratification) scores.
Patients in the Culotte group had significant higher 1-year MACE rate (16.3%), mainly driven by increased TVR (11.0%), compared with the DK group (6.2% and 4.3%, respectively; all p < 0.05). ISR rate in side branch was 12.6% in the Culotte group and 6.8% in the DK group (p = 0.037). Definite ST rate was 1.0% in the Culotte group and 0% in the DK group (p = 0.248). Among patients with bifurcation angle ≥70°, NERS score ≥20, and SYNTAX score ≥23, the 1-year MACE rate in the DK group (3.8%, 9.2%, and 7.1%, respectively) was significantly different to those in the Culotte group(16.5%, 20.4%, and 18.9%, respectively; all p < 0.05).
Culotte stenting for UPLMCA bifurcation lesions was associated with significantly increased MACEs, mainly due to the increased TVR. (Double Kissing DK Crush Versus Culotte Stenting for the Treatment of Unprotected Distal Left Main Bifurcation Lesions: DKCRUSH-III, a Multicenter Randomized Study Comparing Double-Stent Techniques; ChiCTR-TRC-00000151).
Aims Endothelial dysfunction is a key event that links obesity, diabetes, hypertension, and cardiovascular diseases. The aim of the present study was to examine the protective effect of the alkaloid ...drug berberine against hyperglycemia-induced cellular injury and endothelial dysfunction. Methods and results In both cultured endothelial cells and blood vessels isolated from rat aorta, berberine concentration dependently enhanced phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser1177 and promoted the association of eNOS with heat shock protein 90 (HSP90), leading to an increased production of nitric oxide. Furthermore, berberine attenuated high glucose-induced generation of reactive oxygen species, cellular apoptosis, nuclear factor-κB activation, and expression of adhesion molecules, thus suppressing monocyte attachment to endothelial cells. In mouse aortic rings, berberine elicited endothelium-dependent vasodilatations and alleviated high glucose-mediated endothelial dysfunction. All these beneficial effects of berberine on the endothelium were abolished by either pharmacological inhibition of adenosine monophosphate-activated protein kinase (AMPK) or adenovirus-mediated overexpression of a dominant negative version of AMPK. Conclusion Berberine protects against endothelial injury and enhances the endothelium-dependent vasodilatation, which is mediated in part through activation of the AMPK signalling cascade. Berberine or its derivatives may be useful for the treatment and/or prevention of endothelial dysfunction associated with diabetes and cardiovascular disease.
Recent evidence highlights the therapeutic potential of peroxisome proliferator-activated receptor-δ (PPARδ) agonists to increase insulin sensitivity in diabetes. However, the role of PPARδ in ...regulating vascular function is incompletely characterized. We investigate whether PPARδ activation improves endothelial function in diabetic and obese mice. PPARδ knockout (KO) and wild-type (WT) mice fed with high-fat diet and db/db mice were used as diabetic mouse models, compared with PPARδ KO and WT mice on normal diet and db/m(+) mice. Endothelium-dependent relaxation (EDR) was measured by wire myograph. Flow-mediated vasodilatation (FMD) was measured by pressure myograph. Nitric oxide (NO) production was examined in primary endothelial cells from mouse aortae. PPARδ agonist GW1516 restored EDRs in mouse aortae under high-glucose conditions or in db/db mouse aortae ex vivo. After oral treatment with GW1516, EDRs in aortae and FMDs in mesenteric resistance arteries were improved in obese mice in a PPARδ-specific manner. The effects of GW1516 on endothelial function were mediated through phosphatidylinositol 3-kinase (PI3K) and Akt with a subsequent increase of endothelial nitric oxide synthase (eNOS) activity and NO production. The current study demonstrates an endothelial-protective effect of PPARδ agonists in diabetic mice through PI3K/Akt/eNOS signaling, suggesting the therapeutic potential of PPARδ agonists for diabetic vasculopathy.