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Objectives: The aim of this study was to determine the long-term results of mitral valve (MV) repair with anterior leaflet patch augmentation., Methods: Between 2012 and 2015, 45 patients underwent MV repair using the anterior leaflet patch augmentation technique at our institution. The mean age of the patients was 65.9 ± 13.0 years (16 males). We reviewed the MV pathology and the surgical techniques used and assessed the early and late results., Results: In terms of MV pathology, 43 patients (95.6%) had pure mitral regurgitation (MR) and 2 patients (4.4%) had mixed mitral stenosis and MR. Rheumatic changes were seen in 18 patients (40.0%). Postoperative echocardiography showed that 95.6% of patients had none to mild MR. During a median follow-up period of 5.5 years (range 0.1-8.3 years), there were 8 late deaths. Nine patients (20%) required reoperation. The mean interval between the initial operation and redo operation was 3.7 ± 3.1 years (range: 0.4-7.8 years). The causes of reoperation included patch dehiscence (n = 4), progression of mitral stenosis (n = 2), band dehiscence (n = 1), patch enlargement (n = 1) and unknown (n = 1). Eight patients underwent MV replacement and 1 underwent repeat MV repair. The freedom from reoperation at 3 and 5 years was 85.7 ± 6.7% and 81.2 ± 7.7%, respectively., Conclusions: Anterior leaflet patch augmentation can provide excellent early results in the majority of the patients even in the presence of rheumatic pathology; however, we observed late reoperation in 20% of patients. Thus, this technique should be used with caution and careful follow-up with serial echocardiography is essential., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Objectives: Debate continues on whether a bilateral (BLT) or a single lung transplantation (SLT) is preferred for patients with end-stage chronic obstructive pulmonary disease (COPD). The purpose of this study is to examine the interplay between patient age and transplant type on survival outcomes., Methods: We performed a retrospective study of lung transplants for COPD at our centre from February 2012 to March 2020 (n = 186). Demographics and clinical parameters were compared between patients based on their age (≤65 vs >65 years old) and type of transplant (single vs bilateral). Cox proportional hazards regression was also performed. P-values <0.05 were considered significant., Results: Of the 186 patients with COPD who received lung transplants, 71 (38.2%) received BLTs and 115 (61.8%) received SLTs. There was no significant difference in survival outcomes when looking at patients with single versus BLTs (P = 0.870). There was also no difference in survival between the 2 age groups ≤65 versus > 65 years (P = 0.723). The Cox model itself also did not show a statistically significant improvement in survival outcomes (P = 0.126)., Conclusions: Lung transplant outcomes in patients with end-stage COPD demonstrated non-inferior results in patients with an SLT compared to patients with a BLT. When we compared the age groups, neither transplant type showed superior survival benefits, suggesting there may be some utility in an SLT in younger recipients., (Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery 2021.)

AB-FUBINACA M3 was reported to be a major metabolite of the drug, but its in vivo concentration in authentic human solid tissues has not been quantified yet. Another metabolite AB-FUBINACA M4 did not receive much attention previously and also has not been quantified yet in any authentic human specimens. The aims of this study are to establish a sensitive method for quantification of M3 and M4 in solid tissues and to compare the metabolite profile of AB-FUBINACA in authentic human specimens in vivo with that produced by human hepatocytes in vitro. The quantification was performed by liquid chromatography (LC)-quadrupole-ion trap-tandem mass spectrometry (MS-MS), and the characterization by LC-quadrupole Orbitrap MS-MS The limits of quantification of M3 were 10 pg/mL and 60 pg/g, and those of M4 were 100 pg/mL and 600 pg/g in urine and tissues, respectively. In the present work, M3 and M4 were identified and quantified in human lung, liver and kidney obtained from a cadaver for the first time; the concentrations of M3 were 226, 255, 202 and 155 pg/mL or g, and those of M4 14,400, 768, 637 and 1,390 pg/mL or g in urine, lung, liver and kidney, respectively. The peak intensity profiles of seven metabolites in these specimens were compared with that produced by human hepatocytes; the top three metabolites in urine specimen were completely different from those of hepatocytes. M3 was reported as the predominant metabolite in several previous works and M4 was listed as a minor metabolite in only one work, but, in this work, M4 has been found to be the major metabolite in all of the authentic urine, lung, liver and kidney specimens. The M3 plus M4 metabolites in lung or kidney were found most recommendable to prove AB-FUBINACA consumption, when urine specimen is lacking., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In this study, solid tissues such as the lung, liver, kidney and urine were highlighted to profile the AB-PINACA in vivo metabolites in a fatal abuse case, although such metabolite analysis is usually made with urine specimens. We compared the relative peak intensities of in vivo metabolites of AB-PINACA in lung, liver, kidney and urine specimens collected at the autopsy of its abuser with its in vitro metabolites in human hepatocytes. The metabolites of AB-PINACA in tissues were extracted after homogenization. The urine specimen and portions of the extracted metabolites from tissues were firstly hydrolyzed with β-glucuronidase, and the metabolites were extracted. For in vitro experiment, AB-PINACA was incubated with human hepatocytes for 3 h to produce its metabolites. The identification of the in vivo and in vitro metabolites was performed using liquid chromatography (LC)-high-resolution Orbitrap-tandem mass spectrometry (MS-MS), and the relative intensities of these metabolites were measured using low resolution LC-quadrupole-ion trap-MS-MS. Thirteen metabolites of AB-PINACA were characterized in vivo in several human specimens and in in vitro human hepatocytes. They were produced by the terminal amide hydrolysis to carboxylic acid, hydroxylation, carbonyl formation and/or glucuronidation. The most detectable metabolite in the hepatocytes, lung or liver was the one produced by the terminal amide hydrolysis, whereas the top metabolite in the kidney or urine was the one produced by hydroxylation or carbonyl formation on the pentyl side chain after the terminal amide hydrolysis, respectively. At least 12 metabolites of AB-PINACA were detected in authentic human lung, liver or kidney specimen from a cadaver. It is concluded that the postmortem metabolite profiling of AB-PINACA can be fulfilled with solid tissues, and the lung and kidney were most recommendable especially when urine specimen is not available., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Although conventional open repair is our preference for patients with aortic arch aneurysms, we have often chosen thoracic endovascular aneurysm repair (TEVAR) with a handmade branched stent graft (bTEVAR) in high-risk patients. The aim of this study was to compare the midterm clinical outcomes of our bTEVAR technique to those of the open repair., Methods: Between January 2007 and December 2014, we treated 129 patients with aortic arch aneurysm by means of either conventional open repair (OPEN, n = 61) or bTEVAR (n = 68) at our institution., Results: The mean ages were 70.5 ± 12.7 years in the OPEN group and 72.7 ± 12.5 years in the bTEVAR group (P = 0.32). The aetiologies included true aneurysm in 101 patients (78.3%) and chronic dissection in 26 (20.1%). There were 2 (3.3%) in-hospital deaths in the OPEN group and 3 (4.4%) in the bTEVAR group. The mean follow-up duration was 3.0 ± 2.1 years (2.4 ± 1.9 years in the OPEN group and 3.6 ± 2.3 years in the bTEVAR group). There was no difference in 5-year aneurysm-related mortality between groups (10.7% in OPEN vs 12.8% in bTEVAR, P = 0.50). In terms of late additional procedures, however, none were required in the OPEN group, whereas 10 (15.4%) additional endovascular repairs and 4 (6.2%) open repairs were required in the bTEVAR group., Conclusions: Our bTEVAR could be performed with low early mortality, and it yielded similar midterm aneurysm-related mortality to that of conventional open repair. However, these patients undergoing this technique required more late additional procedures than those undergoing conventional open repair., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: The aim of this study was to investigate the effect of the timing of valve surgery on the clinical outcomes of patients with active infective endocarditis (IE) accompanied by cerebral complications., Methods: We retrospectively analysed a cohort of 568 patients, comprising 118 with non-haemorrhagic cerebral infarction (CI), 54 with intracranial haemorrhage (ICH) and 396 without cerebral events (C; control), who underwent surgery for left-sided active IE in 15 Japanese institutes from 2000 to 2011. The mean age was 58.4 ± 16.9 years in the CI group; 54.5 ± 17.4 years in the ICH group and 56.9 ± 16.0 years in the C group. Clinical outcomes were analysed according to the timing of surgery after the diagnosis of CI or ICH was made., Results: In the CI group, there were 9 (7.6%) hospital deaths, 13 (11%) new cerebral events and 1 (0.8%) redo valve surgery. In the ICH group, there were 3 (5.6%) hospital deaths, 8 (14.8%) new cerebral events and 2 (3.7%) redo valve surgeries. In the C group, there were 36 (9.1%) hospital deaths, 23 (5.8%) new cerebral events and 9 (2.3%) redo valve surgeries. Risk factors for hospital death were prosthetic valve endocarditis (P = 0.045), high C-reactive protein (CRP; P < 0.001) and the elderly (P < 0.001) in the CI group. Delayed surgery (2 weeks after CI) seemed result in a higher incidence of hospital death in the CI group. Patients who had surgery between 15 and 28 days or after 29 days from the onset of CI had higher incidences of hospital death [odds ratio 5.90 (P = 0.107) and 4.92 (P = 0.137), respectively] compared with those who had surgery within 7 days. In the ICH group, risk factors for hospital death were high CRP (P = 0.002) and elderly (P < 0.001). Contrary to CI patients, patients who had surgery between 8 and 21 days or after 22 days after the onset of ICH had lower incidences of hospital death [odds ratio 0.79 (P = 0.843) and 0.12 (P = 0.200), respectively] compared with those who had surgery within 7 days., Conclusions: Although statistically insignificant, early surgery in active IE patients with CI is safe, but very early surgery (within 7 days) should be avoided in patients with ICH., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Living-donor lobar lung transplantation (LDLLT) has been performed as a life-saving procedure for critically ill patients who are unlikely to survive the long wait for cadaveric lungs. The purpose of this study was to compare the preoperative condition and outcome of LDLLT patients with those of conventional cadaveric lung transplantation (CLT) patients., Methods: A new lung transplant programme was established in 2008 at Kyoto University. Between June 2008 and January 2014, we performed 79 lung transplants, including 42 LDLLTs (10 single, 32 bilateral) and 37 CLTs (22 single, 15 bilateral). Data collected included pre- and perioperative variables and mid-term survival. All data were analysed retrospectively as of January 2014., Results: The majority of patients were female (57.1%) in the LDLLT group and male (64.9%) in the CLT group. The average age was similar (36.6 ± 20.7 vs 39.7 ± 12.6 years, P = 0.42) between the two groups. Preoperatively, interstitial lung disease was more common in LDLLT patients than in CLT patients (47.6 vs 24.3%, P = 0.048); prior haematopoietic stem cell transplantation was performed more often in LDLLT patients than in CLT patients (33.3 vs 13.5%, P = 0.040) and there were more steroid-dependent LDLLT patients than CLT patients (64.3 vs 29.7%, P = 0.0022). Based on preoperative criteria of lower body mass index (17.2 ± 4.0 vs 19.3 ± 3.3 kg/m(2), P = 0.013), less ambulatory ability (42.9 vs 86.5%, P = 0.0001) and more ventilator dependence (11.9 vs 2.7%, P = 0.12), LDLLT patients were more debilitated than CLT patients. LDLLT patients required longer postoperative mechanical ventilation than CLT patients (15.6 ± 16.2 vs 8.5 ± 8.1 days, P = 0.025). However, 1- and 3-year survival rates were similar between the two groups (89.7 and 86.1% vs 88.3 and 83.1%, P = 0.55). All living donors returned to their previous lifestyles without restriction., Conclusions: Although LDLLT patients were in a worse preoperative condition than CLT patients, LDLLT patients demonstrated survival rates similar to CLT patients. LDLLT is a viable option for patients too ill to survive a long waiting time for cadaveric donors., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

The reaction of rat liver microsomes with Fe(3+), ADP and NADPH was examined using EPR, HPLC-EPR and HPLC-EPR-MS combined use of spin trapping technique. A prominent EPR spectrum (alpha(N) = 1.58 mT and alpha(H)beta = 0.26 mT) was observed in the complete reaction mixture. The EPR spectrum was hardly observed for the complete reaction mixture without rat liver microsomes. The radicals appear to be derived from microsomal components. The EPR spectrum was also hardly observed in the absence of Fe(3+). Addition of some iron chelators such as EDTA, citrate and ADP resulted in the dramatic change in the EPR intensity. Iron ions seem to be essential for this reaction. For the complete reaction mixture with boiled microsomes, a weak EPR spectrum was observed, suggesting that enzymes participate in the reaction. Five peaks were separated on the HPLC-EPR elution profile of the complete reaction mixture of rat liver microsomes with ADP, Fe(3+) and NADPH. The retention times of the peaks 1 to 5 were 19.4, 22.5, 27.3, 29.8 and 31.4 min, respectively. To identify the radical adducts, HPLC-EPR-MS analyses were performed for the three prominent peaks. The HPLC-EPR-MS analyses showed that a new radical adduct, 4-POBN/1-hydroxypentyl radical, in addition to 4-POBN/ethyl radical adducts, forms in a reaction mixture of rat liver microsomes with ADP, Fe(3+) and NADPH.

Our recent work on the gene structures for human salivary (S-type) cystatins [Saitoh, E. et al. (1987) Gene 61, 329-338] has suggested that the structures of cystatins which we determined previously at the protein level lack N-terminal peptide portions of the full-sized intact forms. In the present study, attempts were made to isolate full-sized S-type cystatins by introducing methanol fractionation into the purification steps to suppress the enzymatic activity present in saliva. Full-sized cystatin SN and two phosphorylated forms of full-sized cystatin S were thus isolated. Analysis of one fraction indicated that this was a mixture of full-sized cystatin SA and non-phosphorylated cystatin S. The phosphorylation sites of cystatin S were determined to be Ser-Ser-Ser1(P)-Lys-Glu-Glu- for monophosphorylated cystatin S and Ser1(P)-Ser-Ser3(P)-Lys-Glu-Glu- for diphosphorylated cystatin S. Immunoblotting analysis with anti-cystatin S antiserum revealed that tears and seminal plasma also contained S-type cystatins, but diphosphorylated cystatin S was detected neither in tears nor in seminal plasma and no cystatin SN was found in seminal plasma. These data indicate that S-type cystatins are secreted into the oral cavity without significant degradation in salivary glands or ducts and that they are expressed tissue specifically.