Comparison of Exercise Echocardiography in Patients with 18mm ATS-AP Aortic Prosthesis

There have been various arguments concerning the patient-prosthesis mismatch (PPM) after aortic valve replacement (AVR) for small valves. The objective of this study was to evaluate the postoperative hemodynamics in patients. Methods: The subjects were 6 patients [6 females aged 64 (17~74) years, with a median body surface area (BSA) of 1.37 (1.29~1.51) m2] who underwent AVR at our facility using the 18-mm ATS-AP and tolerated exercise loading. We estimated pressure gradient(PG) ,ejection fraction(EF), left ventricular mass Index(LVMI)at pre-operation and post-operation. Exercise echocardiography on an ergometer was performed before and 29.0 ± 14.4 months after surgery. We estimated PG and effective orifice area(EOAI) at rest and at exercise. We compared echo data between pre-operation and post-operation, between at rest and at exercise. Results: The effective orifice area index(EOAI) at rest was 0.92(0.75~1.06) cm2/m2. There was a significant change in the LVMI between pre-operation and post-operation[158.5(104.0~222.2) g/m2 versus 102.4(92.3~146.4) g/m2; P 0.05] and mean PG[11.0(6.6~16) mmHg versus 14.0(6.3~16) mmHg; P > 0.05], on maximal exercise. Conclusion: In patients whose BSA were 1.37(1.29~1.51) m2,the 18-mm ATS-AP was suggested to be a prosthetic valve that improves myocardial remodeling and provides stable hemodynamics even during exercise

Operative Outcome of Cardiac Surgery in Patients with Liver Cirrhosis

Introduction: A retrospective study was performed to investigate the relationship between the severity of liver cirrhosis and the outcome of cardiac surgery. Methods and Results: Twenty-one patients with liver cirrhosis underwent cardiac surgery in our institution. According to the Child-Pugh classification, 13 patients were in class A, 7 in class B, and 1 in class C. Coronary artery bypass grafting was performed in 7 patients, surgery for valvular disease in 10 and other procedures in 4. Major postoperative complications occurred in 8%, 29%, and 100% for Child-Pugh class A, B, and C, respectively. Preoperative hemoglobin level was significantly lower in the patients with postoperative complications. None of 4 patients underwent coronary revascularization using off-pump procedure or mini-pump system experienced major complication. The operative mortality was 0%, 14%, and 0% for Child-Pugh class A, B, and C, respectively. Conclusions: Although the overall mortality rate in patients with liver cirrhosis was acceptable in our study, the incidence of severe complications, such as prolonged ventilation, mediastinitis and irreversible hepatic insufficiency was problematic in Child-Pugh class B and class C patients. Application of less invasive cardiac surgery, such as mini-pump system or off-pump procedure will improve the operative outcome in such patient group.長崎大学学位論文 学位記番号:博（医）甲第1,272号学位授与年月日:平成20年7月16

Surgical experience with chronic constrictive pericarditis

Objective: Constrictive pericarditis is a disease characterized by marked thickening of the pericardium which causes restriction of diastolic cardiac function. The purpose of this report is to review the outcome of pericardiectomy for constrictive pericarditis and to discuss its problems. Methods: Sixteen consecutive patients who underwent pericardiectomy for constrictive pericarditis in our institution between March 2000 and June 2011 were reviewed. All patients underwent decortication including at least the anterior surface from the right atrium to the left phrenic nerve and the diaphragmatic surface of the heart. The epicardium was concomitantly resectioned because it was usually sclerotic and constrictive. Results: Postoperatively, mean central venous pressure decreased to 8.8 ± 3.1 mmHg and was significantly lower than the preoperative value 15.3 ± 3.7 mmHg (p < 0.001). The mean postoperative duration of hospitalization was 25.6 ± 13.5 days. There were 2 in-hospital deaths and early mortality rate was 12.5 %; however, excluding hospital deaths, there were no significant postoperative complications and all survivors recovered and maintained good cardiac function during the mean follow-up period of 3.7 ± 2.8 years. Conclusion: For an acceptable outcome, surgical intervention should be performed at an appropriate time and the pericardiectomy should have proper scope and depth to prevent irreversible changes in the heart, liver, and other organs

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

A Case of Pulmonary Artery Aneurysm Related to Pulmonary Valve Regurgitation

A 56-year old woman was admitted to our institution for the treatment of pulmonary artery aneurysm and pulmonary valve regurgitation. Multislice three-dimensional computed tomography showed a very large (61 mm in diameter) pulmonary artery aneurysm. Transthoracic echocardiography revealed severe pulmonary valve regurgitation and an enlarged right ventricle. Pulmonary artery aneurysmorrhaphy and pulmonary valve replacement were performed. Postoperative hemodynamics were stable. No recurrent dilatation of the pulmonary artery or cardiac failure was observed 9 months after surgery

Vacuum-assisted closure therapy for salvaging a methicillin-resistant Staphylococcus aureus-infected prosthetic graft

Infection of a vascular prosthesis after a bypass surgery is relatively rare. However, once developed, serious complications can occur, such as bleeding, sepsis, and organ ischemia, occasionally resulting in leg amputation or even death in some cases. The treatment of a vascular prosthesis infection involves the necessary removal of the infected graft, subsequently, an extra-anatomical bypass surgery is often considered. We herein report a case in which postoperative methicillin-resistant Staphylococcus aureus infection caused dehiscence of the femoral vessels and exposure of the graft vessel and anastomosed area. The infected tissue was surgically removed (debridement), and the patients condition was successfully treated by the application of a nonadherent dressing and vacuum-assisted closure therapy combined with the bridging technique

Expression of CXCL12 in esophageal high grade dysplasia characterized pathologically by lymphocyte accumulation directly under the lesion

Squamous dysplasia of the esophagus is an unequivocal neoplastic alteration of the esophageal squamous epithelium without invasion. Esophageal high grade dysplasia (EHGD) is characterized by >50% epithelial involvement or severe cytological atypia. Frequently, lymphocytes accumulate below EHGD lesions even though there is no invasion. If this lymphocytic accumulation is active, a transmitter should exist between the EHGD cells and the lymphocytes. CX-C motif chemokine ligand (CXCL) 12, CXCL10 and C-C motif chemokine ligand 18 (CCL18) are all lymphocyte chemoattractants in vivo, but there are no reports on the relationship between these chemokines and EHGDs. In this study, we investigated these chemokines and C-X-C motif chemokine receptor 4 (CXCR4) (receptor for CXCL12) in 30 EHGDs using immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). For comparison, we enrolled 30 samples of normal esophageal squamous epithelium (NESE). We confirmed CXCL12 expression (H-score≥50 points) in 70% of EHGD and 0% of NESE samples, CXCL10 expression in 3% of EHGD and 3% of NESE samples, CCL18 expression in 3% of EHGD and 0% of NESE samples, and CXCR4 expression in 53% of EHGD and 0% of NESE samples by immunohistochemistry. EHGD and NESE cases were significantly different in their expressions between the tissue types (CXCL12, p<0.001; CXCR4, p<0.001). We examined CXCL12 and CXCR4 mRNA expressions of 3 representative EHGD samples, each having their respective immunostained areas detected by RT-PCR. Finding CXCL12 expression may indicate that this chemokine plays a part in the lymphocyte accumulation that occurs directly under EHGDs

Vacuum-assisted closure therapy for salvaging a methicillin-resistant Staphylococcus aureus-infected prosthetic graft

Infection of a vascular prosthesis after a bypass surgery is relatively rare. However, once developed, serious complications can occur, such as bleeding, sepsis, and organ ischemia, occasionally resulting in leg amputation or even death in some cases. The treatment of a vascular prosthesis infection involves the necessary removal of the infected graft; subsequently, an extra-anatomical bypass surgery is often considered. We herein report a case in which postoperative methicillin-resistant Staphylococcus aureus infection caused dehiscence of the femoral vessels and exposure of the graft vessel and anastomosed area. The infected tissue was surgically removed (debridement), and the patient's condition was successfully treated by the application of a nonadherent dressing and vacuum-assisted closure therapy combined with the bridging technique