Multiset partial least squares with rank order of groups for integrating multi-omics data

As more multi-omics data such as metabolome, proteome and transcriptome data are acquired, statistical analyses to integrate multi-omics data has been required. Multivariate analysis for integration of multi-omics data has been proposed such as multiset partial least squares (PLS). However, when we want to extract scores about the rank order of groups such as severity of disease as well as difference of groups, we could not always extract scores with rank order of groups by using multiset PLS. Therefore, we proposed multiset PLS with rank order of groups (multiset PLS-ROG) to integrate multiple omics dataset. We visualized multiple omics data by using multiset PLS-ROG in two studies of multi-omics and multi-organ derived metabolome data. After we visualize data and focus on a specific score with phenotype of interest, it is important to select compounds to identify biomarker candidates or make biological inferences. In ordinary principal component analysis (PCA) or PLS, we could select statistical significantly compounds correlated with PC or PLS score by using PC or PLS loadings. However, multiset PLS loading has not been used because its statistical property has not been clarified. Then, we clarified statistical property of multiset PLS and multiset PLS-ROG loading, and we could identify statistically significant compounds by using statistical hypothesis testing. We implemented multiset PLS-ROG to R loadings package, freely available in CRAN.

Subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques

SARS-CoV-2 infection presents clinical manifestations ranging from asymptomatic to fatal respiratory failure. Despite the induction of functional SARS-CoV-2-specific CD8+ T-cell responses in convalescent individuals, the role of virus-specific CD8+ T-cell responses in the control of SARS-CoV-2 replication remains unknown. In the present study, we show that subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques. Eight macaques were intranasally inoculated with 105 or 106 TCID50 of SARS-CoV-2, and three of the eight macaques were treated with a monoclonal anti-CD8 antibody on days 5 and 7 post-infection. In these three macaques, CD8+ T cells were undetectable on day 7 and thereafter, while virus-specific CD8+ T-cell responses were induced in the remaining five untreated animals. Viral RNA was detected in nasopharyngeal swabs for 10-17 days post-infection in all macaques, and the kinetics of viral RNA levels in pharyngeal swabs and plasma neutralizing antibody titers were comparable between the anti-CD8 antibody treated and untreated animals. SARS-CoV-2 RNA was detected in the pharyngeal mucosa and/or retropharyngeal lymph node obtained at necropsy on day 21 in two of the untreated group but undetectable in all macaques treated with anti-CD8 antibody. CD8+ T-cell responses may contribute to viral control in SARS-CoV-2 infection, but our results indicate possible containment of subacute viral replication in the absence of CD8+ T cells, implying that CD8+ T-cell dysfunction may not solely lead to viral control failure. Author SummarySARS-CoV-2 infection presents a wide spectrum of clinical manifestations ranging from asymptomatic to fatal respiratory failure. The determinants for failure in viral control and/or fatal disease progression have not been elucidated fully. Both acquired immune effectors, antibodies and CD8+ T cells, are considered to contribute to viral control. However, it remains unknown whether a deficiency in either of these two arms is directly linked to failure in the control of SARS-CoV-2 replication. In the present study, to know the requirement of CD8+ T cells for viral control after the establishment of infection, we examined the effect of CD8+ cell depletion by monoclonal anti-CD8 antibody administration in the subacute phase on SARS-CoV-2 replication in cynomolgus macaques. Unexpectedly, our analysis revealed no significant impact of CD8+ cell depletion on viral replication, indicating that subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells. CD8+ T-cell responses may contribute to viral control in SARS-CoV-2 infection, but this study suggests that CD8+ T-cell dysfunction may not solely lead to viral control failure or fatal disease progression.

Stent-Graft Re-expansion Following Axillo-Bifemoral Bypass : A Case of Stent Graft Collapse due to Acute Type B Aortic Dissection / 日本心臓血管外科学会雑誌

We describe a rare complication and treatment progression that occurred in a 64-year-old man with an aortic abdominal aneurysm (AAA) that had been treated by endovascular aneurysm repair (EVAR). He had undergone EVAR to treat an infra-renal type AAA 21 months previously and returned to the emergency department with back pain. Contrast-enhanced computed tomography (CT) revealed acute type B aortic dissection, so he was admitted and conservative medical management was started. Acute stomachache and limb pain appeared on hospital day 7, which prevented him from moving his lower limbs. The main body of the stent graft had collapsed, blocking blood flow, and contrast was not found in arteries from the collapsed stent graft portion to the knee level on emergency contrast CT images of the leg. His legs were revascularized by an extra-anatomical right axial-bilateral external iliac bypass. His symptoms disappeared and reperfusion injury was avoided. The collapsed stent graft had retained its original shape at 11 and 18 days after surgery. Furthermore, follow-up CT 4.5 years later showed that the stent graft retained its original form.

Introduction of Laparoscopic Partial Liver Resection:Analysis of the First 60 Consecutive Cases / 日本農村医学会雑誌

　　Safe introduction of laparoscopic partial liver resection (LPLR) requires the selection of appropriate cases not exceeding the surgeon's skills as well as standardization of surgical procedures. After introduction at our institution, 60 LPLR procedures were performed between April 2010 and May 2016. To identify indices for case selection, short-term perioperative parameters were analyzed, including operative time, blood loss, postoperative complications, and postoperative hospital stay. Operative time was significantly shorter in the last 30 cases compared with the first 30 cases (182.5 min vs. 253 min; p＝0.023) and in 16 cases involving the left lobe (S2-4) compared with 44 cases involving the right lobe (S1, S5-8; 148.5 min vs. 246 min; p＝0.004). Blood loss was significantly less (0 mL vs. 50 mL; p＝0.028) and operative time was significantly shorter (185 min vs. 250 min; p＝0.048) in 27 cases with tumor diameter ＜2.5 cm compared with 33 cases with tumor diameter ≥ 2.5 cm. Operative time tended to be longer in 9 cases of multiple-site resection compared with 51 cases of single-site resection (207 min vs. 260 min; p＝0.085). BMI, pathology, and hepatitis virus status showed no significant difference in perioperative short-term results. For the introduction of LPLR, it may be preferable to select cases located in the left lobe with a tumor diameter ＜2.5 cm and to accumulate a certain amount of experience in similar cases first.

A Case of Late Surgical Conversion for Type II Endoleak after EVAR / 日本心臓血管外科学会雑誌

Type II endoleak after stent graft for abdominal aortic aneurysm generally permits a wait-and-see approach, however, additional second therapy is necessary if the aneurysm increases. A 78-year-old woman had undergone endovascular treatment with a stent-graft for abdominal aortic aneurysm. Computed tomography (CT) 3 months after the operation showed type II endoleak, and enlargement of the aneurysm was noted at 1 year. She underwent transarterial embolization for third and fourth lumbar arteries, but endoleak from the fourth lumbar artery remained, and the aneurysm was further enlarged. Surgical conversion was performed 2 years after the first operation. We applied a ligature to the forth lumbar artery by a laparotomy. Postoperative CT revealed disappearance of the endoleak. As endovascular treatment for abdominal aortic aneurysm is increasing and the number of cases necessitating additional therapy appears to be rising, we need to develop processes and strategies for coping with endoleaks.

A Case of Aortic Valve Papillary Fibroelastoma with Atrial Septal Defect / 日本心臓血管外科学会雑誌

A 68-year-old woman with a diagnosis of atrial septal defect (ASD) presented with dyspnea. Chest radiography demonstrated cardiomegaly and infiltration in both lungs, suggestive of cardiac decompensation due to ASD. Detailed evaluation with transthoracic echocardiography revealed a mobile tumor on the aortic valve. Intraoperatively, tumors were identified on all aortic cusps. Preservation of the aortic valve was difficult. We therefore performed aortic valve replacement and patch closure of the ASD. The existing literature suggests that mobile papillary fibroelastoma should be excised irrespective of size, to prevent the risk of embolism. Excision of the tumor alone is usually sufficient. However, the present case showed clustered tumors on the aortic valve, so preservation of the cusps could not be achieved in this case.

Renal Function and Mortality in Patients with Infective Endocarditis / General Medicine

<b>Objectives:</b> Infective endocarditis (IE) has an extremely poor prognosis unless appropriate treatment is received. Hemodialysis patients with IE show higher rates of morbidity and mortality in comparison with non-dialysis patients with IE. We focused on hemodialysis patients, as well as patients in other stages of chronic kidney disease. We sought to assess the relationship between renal function and mortality in patients with IE.<br><b>Methods:</b> We carried out a retrospective cohort study on 45 consecutive patients with IE in an urban teaching hospital between November 2003 and August 2008. We collected demographic and clinical data as well as pre- and post-discharge outcomes. Patients were subdivided into four groups according to their eGFR level at admission: A: eGFR≧60 ml/min/1.73 m² (n=23); B: eGFR 30-59 ml/min/1.73 m² (n=15); C: eGFR<30 ml/min/1.73 m² (n=3); and, D: dialysis patients (n=3). It was not possible to determine the outcome status of one patient. The Trend Test was used to evaluate the association between renal function and mortality.<br><b>Results:</b> There were 29 male and 16 female patients with IE and the mean age was 67.9+-17.6 (SD). There were 10 diabetic patients (22%). Thirty-nine patients (84%) were either discharged or transferred to another hospital. Seven patients (16%) died: two (9%) Group A patients; three (20%) Group B patients; no Group C patients; and, two (67%) Group D patients. Patients with lower eGFR had higher mortality rates (Trend Test, P=0.046).<br><b>Conclusion:</b> We presume a trend towards a higher mortality rate in conjunction with advancing CKD stage.

Hybrid Endovascular Stent Graft Repair with Reconstruction of Superior Mesenteric and Celiac Arteries for a Ruptured Thoracoabdominal Aortic Aneurysm / 日本心臓血管外科学会雑誌

A 77-year-old woman was referred to our hospital for treatment of a ruptured thoracoabdominal aortic aneurysm (TAAA) with a maximum diameter of 7cm. Considering her age and level of daily activity, the placement of an endovascular stent graft was performed as an emergency rescue procedure. For termination of the endoleak from the distal portion of the stent graft detected by CT the next day, another stent graft placement was added after establishment of blood supply to the superior mesenteric and celiac arteries by placing a Y-shaped graft from the abdominal aorta to each artery with success. The patient was discharged from our hospital 25days after surgery with disappearance of endoleak and good graft patency. A hybrid technique with grafting to abdominal branches, followed by placement of stent graft, can be an alternative treatment for such high-risk patients with ruptured TAAA.

Induction of apoptosis in RKO colon cancer cell line by an aqueous extract of Millingtonia hortensis.

Millingtonia hortensis is an important medicinal plant in Southeast Asia, used for the treatment of asthma, sinusitis and as a cholagogue and tonic. The aim of this study was to compare the effects of aqueous and ethanol extracts of Millingtonia hortensis on the induction of apoptosis in an RKO human colon cancer cell line. Viability of RKO cells was assessed by MTT reduction assay. The aqueous extract, but not the ethanol extract of M. hortensis inhibited cell growth and proliferation in a dose- and time-dependent manner. Apoptotic cells were determined by flow cytometry and DNA fragmentation assay. Apoptotic cell numbers increased in a dose-dependent manner after treatment with aqueous extract. DNA ladders were clearly observed in RKO cells treated with 200, 300 and 400 ?g/ml of the aqueous extract of M. hortensis for 48 h. These results indicate that the aqueous extract of M. hortensis inhibited cell proliferation in an RKO colon cancer cell line via the apoptosis pathway.

Aortic Valve Replacement for Severe Aortic Stenosis with Severe Left Ventricular Dysfunction / 日本心臓血管外科学会雑誌

There is disagreement regarding the indications of surgery for cases of severe aortic stenosis (AS) with a decrease in left ventricular ejection fraction (EF) and a low aortic pressure gradient (PG), since there is a high perioperative risk associated with this condition. Hence, we investigated the surgical outcome of AS cases with impaired left ventricular function. Our department performed 144 aortic valve replacements (AVRs) for cases of AS and AS-dominant mild regurgitation (ASr) between January 2000 and September 2005. Among these cases, 9 patients had an EF under 35%, and these patients were selected as subjects and compared with a control group with an EF of more than 35%. Patients with accompanying coronary artery diseases that required treatment were excluded to avoid confounding effects on cardiac function. The mean age of the 9 subjects (4 men and 5 women) was 67.8±10.8 years old, with a range from 53 to 80 years old, and the subjects had the following mean background data: EF, 34.4±0.5%; left ventricular end-diastolic dimension (LVDd), 57.3±5.8mm; left ventricular end-systolic dimension (LVDs), 49.3±5.7mm; interventricular septum thickness (IVSth), 11.9±1.9mm; and left ventricular posterior wall thickness (LVPWth), 11.1±2.6mm. Characteristics such as left ventricular dilatation and thinning of the left ventricle myocardium were noted in these data. The cases were classified as severe AS because the mean aortic valve area (AVA) was 0.58±0.2cm², but the peak aortic pressure gradient (peak PG) (65.2±32.7mmHg) in the 9 subjects was lower than that of the control group (97.0±65.2mmHg). All 9 subjects underwent aortic valve replacements (AVRs), with simultaneous mitral annuloplasty (MAP) in 3 cases, mitral valve replacement (MVR) in 1 case and performance of a Maze procedure in 1 case. No deaths occurred while the patients were in hospital. Postoperative complications included 2 cases of transient atrial fibrillation and 1 case of postoperative bleeding requiring rethoracotomy for hemostasis. The EF in the late postoperative period showed improvement in 8 cases and was unchanged in the remaining case; the mean postoperative EF was 56.9% for the 9 subjects. All cases were rated as improved based on the NYHA classification of cardiac performance, and the significant improvement in EF in 8 of the 9 cases suggests that surgery is safe and can improve prognosis for patients with advanced AS with myocardium thinning and decreased EF.

Comparison of Early and Midterm Result of Endovascular Aneurysm Repair and Open Repair in the Treatment of Abdominal Aortic Aneurysms / 日本心臓血管外科学会雑誌

To evaluate a comparison for endovascular repair (EVAR) versus open repair (OR) for the treatment of abdominal aortic aneurysm (AAA). Data of all patients with infrarenal AAA treated electively, both with OR (107 cases) and EVAR (24 cases), at our institute between January 1999 and March 2004 were retrospectively reviewed. No difference was found between the 2 groups for sex, age, and AAA size. Cases of chronic obstructive pulmonary disease (20.8% vs 6.5%, <i>p</i><0.04) and frequencies of laparotomy (25% vs 2.8%, <i>p</i><0.001) were significantly more in the EVAR group than the OR group. In the initial results, deployment of the stent grafts was successful in all cases and complete thrombosis of the aneurysm was achieved in 21 cases (87.5%). One graft occlusion and a wound infection occurred in the EVAR group. OR was successfully performed in all cases. These were 6 cases of paralytic ileus, 1 of re-operation for hemorrhage, 1 of respiratory failure, and 1 of ischemic colitis in the OR group. One hospital death occurred in each group. Mean blood transfusion (0ml vs 238±345ml) and operation time (131±53min vs 250±76min) were significantly less in the EVAR group than the OR group. In the long term results, the cumulative survival rate was 88.0±6.5% at 1 and 2 years, 80.6±9.2% at 3 years in the EVAR group; 99.0±0.9% at 1 year, 94.1±2.6% at 2 years, 87.7±3.9% at 3 years in the OR group, with no difference between the 2 groups regarding survival rate. Four new endoleak and 3 graft infections were encountered in the EVAR group. Freedom from stent graft-related complications was 81.3±8.5% at 1 year, 61.4±11.9% at 2 years, 47.8±12.6% at 3 years in the EVAR group, but 100% at 1, 2 and 3 years in the OR group. Freedom from procedure-related complications in the EVAR group was significantly lower than that in OR group. In the long term results, EVAR was associated with more procedure-related complications. This finding may justify reappraisal of currently accepted EVAR for AAA management strategies.