Analysis of B-cell receptor repertoire to evaluate immunogenicity of monovalent Omicron XBB.1.5 mRNA vaccines.

Monovalent Omicron XBB.1.5 mRNA vaccines were newly developed and approved by the FDA in Autumn 2023 for preventing COVID-19. However, clinical efficacy for these vaccines is currently lacking. We previously established the quantification of antigen-specific antibody sequence (QASAS) method to assess the response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination at the mRNA level using B-cell receptor (BCR) repertoire assay and the coronavirus antibody database (CoV-AbDab). Here, we used this method to evaluate the immunogenicity of monovalent XBB.1.5 vaccines. We analyzed repeated blood samples of healthy volunteers before and after monovalent XBB.1.5 vaccination (BNT162b2 XBB.1.5 or mRNA-1273.815) for the BCR repertoire to assess BCR/antibody sequences that matched SARS-CoV-2-specific sequences in the database. The number of matched unique sequences and their total reads quickly increased 1 week after vaccination. Matched sequences included those bound to the Omicron strain and Omicron XBB sublineage. The antibody sequences that can bind to the Omicron strain and XBB sublineage revealed that the monovalent XBB.1.5 vaccines showed a stronger response than previous vaccines or SARS-CoV-2 infection before the emergence of XBB sublineage. The QASAS method was able to demonstrate the immunogenic effect of monovalent XBB.1.5 vaccines for the 2023-2024 COVID-19 vaccination campaign.

Growing Renal Vein Aneurysm Treated by Endovascular Repair: A Case Report and Literature Review.

Renal vein aneurysm (RVA) is extremely rare and often asymptomatic, disclosed only incidentally on diagnostic imaging modalities such as computed tomography and ultrasonography. Management is often just watchful follow-up, but some patients require intervention. We present the case of a 74-year-old man complaining of lower back pain in whom a 53-mm RVA was identified. He underwent successful endovascular repair using Amplatzer vascular plugs. The aneurysm had completely resolved by 12 months. Endovascular treatment of a primary RVA does not seem to have been reported previously. This is a milestone case in the management of RVA.

Mitral valve nonbacterial thrombotic endocarditis: a rare multi-surgery-tolerant survivor of Trousseau's syndrome.

BACKGROUND: Few previous reports have documented cases of nonbacterial thrombotic endocarditis associated with Trousseau's syndrome for which surgery proved possible for both the primary tumor and the cardiac lesion. The effectiveness of direct oral anticoagulants in patients with Trousseau's syndrome has also received scant attention. CASE PRESENTATION: A 69-year-old man with repeated episodes of cerebral infarction was diagnosed as having nonbacterial thrombotic endocarditis after mitral valve replacement surgery. Stroke recurred preoperatively under apixaban administration. A stomach biopsy also identified gastric adenocarcinoma, and gastric surgery was performed on the 40th postoperative day. The patient was discharged from the hospital and has been free of thromboembolism under a regime of subcutaneous heparin self-injection thereafter. CONCLUSIONS: We have reported a rare multi-surgery-tolerant survivor of Trousseau's syndrome in whom subcutaneous heparin injection was useful for preventing thromboembolic events over a long period.

Platypnea-orthodeoxia syndrome associated with aortic insufficiency and aortic elongation.

An 81-year-old female developed dyspnea only upon assuming a sitting position. Trans-esophageal echocardiography demonstrated left-to-right shunt flow across the atrial septum when the patient was sitting, and right-to-left shunt flow when she was supine, along with severe aortic insufficiency. She was diagnosed as having platypnea-orthodeoxia syndrome and her symptoms were completely resolved following aortic valve replacement, closure of a patent foramen ovale, and shortening of an elongated ascending aorta.

[Surgical treatment in an adult with coronary artery aneurysm at proximal site of left anterior descending artery; report of a case].

A 52-year-old man was admitted to our hospital with complaint of chest pain and abnormal electrocardiogram (ECG) findings showing ST depression in V2-V6. Coronary computed tomography (CT) and coronary arteriography (CAG) showed coronary artery aneurysm at #5 [left main trunk (LMT)] 20 mm, #11 [circumflex artery (Cx)] 8.3 mm, RV branch 4 mm, and severe stenosis at #5 and #11. Therefore, his chest pain was due to thromboembolism from coronary artery aneurysm. In the present case, Kawasaki disease was not diagnosed in childhood. Coronary artery aneurysms were rare in the elderly and were usually found in association with Kawasaki disease. Morphological evaluation findings strongly suggested that the coronary artery aneurysm were related to Kawasaki disease. Resection of coronary artery aneurysm and coronary artery bypass grafting [left internal thoracic artery (LITA) to #8 and saphenous vein graft (SVG): aorta (Ao) to #14] were successfully performed. We report a case of coronary artery aneurysms presumed to be due to childhood Kawasaki disease in an elderly man.

Bentall procedure in a patient with severely calcified "porcelain" aorta.

Patients with severe calcified "porcelain" aorta carry a high operative risk during cardiac surgery. We report the successful case of Bentall procedure in a patient with severe porcelain aorta. A 65-year-old woman was diagnosed with aortic prosthetic valve failure and enlargement of the ascending aorta. Preoperative chest X-ray and computed tomography scan revealed heavy calcification throughout the aorta. At operation, cardiopulmonary bypass was established through the right axillary artery. The calcified aorta was transected by an oscillating saw under hypothermic circulatory arrest. Distal anastomosis was performed after endarterctomy of the calcified plate, which allowed us to complete the Bentall procedure without the postoperative bleeding.

Enhanced angiogenesis by gelatin hydrogels incorporating basic fibroblast growth factor in rabbit model of hind limb ischemia.

Recently we have developed new sustained release system of basic fibroblast growth factor (bFGF) using gelatin hydrogel as a carrier. Using this system, we examined the effect of topical sustained release of bFGF on angiogenesis and tissue blood perfusion in a rabbit model of hind limb ischemia. Thirty-two rabbits underwent excision of right femoral artery under general anesthesia. Two weeks later the rabbits were randomized into four groups (n = 8 each): no treatment, intramuscular injection of gelatin hydrogel alone, and intramuscular injection of gelatin hydrogel incorporating 30 microg and 100 microg of bFGF. Four weeks after each treatment, selective angiography, tissue blood flowmetry using laser Doppler perfusion imaging, and histological examination of thigh muscle were performed. In groups treated with bFGF incorporating gelatin hydrogel, tissue blood flow, number of arterioles, and vascular density were significantly increased in a dose-dependent manner 4 weeks after the treatment. Serum concentrations of bFGF and vascular endothelial growth factor were not elevated 4 weeks after the treatment. In conclusion, sustained release of bFGF using gelatin hydrogel augmented angiogenesis and improved tissue blood flow after excision of the femoral artery.

Multislice computed tomography accurately quantifies left atrial size and function after the MAZE procedure.

BACKGROUND: Although the MAZE procedure allows for the recovery of sinus rhythm and left atrial (LA) mechanical function in the great majority of patients with chronic atrial fibrillation (AF), the effects of MAZE on the precise LA geometry and wall motion remain to be elucidated. We hypothesized that LA size and mechanical function in patients with chronic AF and mitral valvular disease are well restored after MAZE. METHODS AND RESULTS: We studied 14 patients (MAZE group: mean+/-SD age, 63.9+/-8.6 years; 8 men and 6 women) who underwent MAZE for chronic AF and mitral valve surgery and 10 patients with sinus rhythm (coronary artery bypass graft [CABG] group: age, 70.0+/-7.9 years; 5 men and 5 women) who underwent CABG at Takeda Hospital between February 2002 and September 2005. MAZE was conducted by the endocardial application of radiofrequency ablation with a temperature-controlled multipolar radiofrequency catheter. LA volume and booster function were quantitatively evaluated by multislice computed tomography at 17.9+/-10.0 months (MAZE group) and 15.3+/-13.6 months (CABG group) postoperatively. All patients with MAZE were free of AF and other atrial arrhythmias during the follow-up period. In the CABG group, LA maximal and minimal volumes and ejection fraction were 109+/-12 mL, 82+/-11 mL, and 26+/-10%, respectively. In the MAZE group, LA maximal volume was 139+/-17 mL (P=0.187 versus CABG), and LA minimal volume was 121+/-16 mL (P=0.082 versus CABG), with an ejection fraction of 15+/-7% (P=0.004 versus CABG). In both groups, all parts of the LA wall contracted toward the geometric center of the LA. The extent of wall motion was significantly worse in the MAZE group compared with the CABG group. In both groups, LA booster function was inversely correlated with LA maximal volume. CONCLUSIONS: MAZE with radiofrequency ablation is safe and effective for the restoration of sinus rhythm in patients with chronic AF and mitral valve disease. However, chronic AF associated with mitral valve disease deteriorates LA mechanical function diffusely throughout the LA wall. Further studies with the use of multislice computed tomography are needed to sequentially evaluate LA function after MAZE in patients with and without mitral valve surgery.

Prostaglandin E2 EP4 receptor-selective agonist facilitates sternal healing after harvesting bilateral internal thoracic arteries in diabetic rats.

OBJECTIVE: Sternal wound complications are devastating events occurring in coronary artery bypass surgery, particularly in patients with diabetes. Prostaglandin E2 receptors have 4 subtypes, and the activation of the EP4 receptor induces bone regeneration. The present study investigated the utility of a prostaglandin E2 EP4 receptor-selective agonist in sternal healing after median sternotomy with the removal of the bilateral internal thoracic arteries in diabetic rats. METHODS: Diabetic Wistar rats with blood glucose levels of greater than 400 mg/dL were established by means of a single intraperitoneal injection of streptozotocin. After median sternotomy and bilateral internal thoracic artery removal in 16 diabetic rats, 8 rats were administered the EP4 agonist (300 microg) on the posterior table of the sternum (EP4 group), whereas 8 did not receive any treatment (control group). Sternal healing and incidence of sternal wound complications were evaluated 4 weeks after the operation. RESULTS: Sternal wound complications developed in 5 rats in the control group but in only 1 rat in the EP4 group (P < .01). Histologic examination revealed an almost completely healed sternum filled with regenerated bone tissue only in the EP4 group. Both bone mineral content and bone mineral density, as assessed with dual-energy x-ray absorptiometry, were higher in the EP4 group than in the control group (71.7 +/- 12.1 vs 48.9 +/- 11.7 mg for bone mineral content [P < .01] and 66.8 +/- 14.6 vs 47.9 +/- 6.3 mg/mm2 for bone mineral density [P < .05]). CONCLUSIONS: The prostaglandin E2 EP4 agonist accelerated the sternal healing and decreased the incidence of sternal wound complications in the diabetic ischemic sternum. This method might help in decreasing sternal necrosis in high-risk patients or permit wider application of bilateral internal thoracic arteries in coronary artery bypass surgery, even in patients with diabetes.

Simultaneous application of basic fibroblast growth factor and hepatocyte growth factor to enhance the blood vessels formation.

OBJECTIVE: The present study investigated whether the simultaneous application of basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF) enhances blood vessel formation in murine ischemic hindlimb compared with bFGF or HGF applied alone. METHODS: Unilateral hindlimb ischemia was created in C57BL/6 mice. Hindlimb blood flow was evaluated by laser Doppler perfusion image index (LDPII) (ratio (%) of ischemic-to-normal-limb blood flow). The ischemic limbs were treated with bFGF and HGF separately, or bFGF and HGF together, and their therapeutic effects were assessed. Collagen microspheres (CM) were used as a sustained-release carrier for bFGF and HGF. RESULTS: A single intramuscular injection of 5 microg or less of bFGF-incorporated CM (bFGF/CM) into the ischemic limb did not significantly increase the LDPII compared with the control (no treatment) 4 weeks after the treatment. Similarly, 20 microg or less of HGF/CM did not increase LDPII. Based on these results, we compared the dual release of CM incorporating 5 microg of bFGF and 20 microg of HGF with either the single release of 5 mug of bFGF/CM alone or 20 microg of HGF/CM alone. The LDPII of the dual release (94.2% +/- 10.9%) was higher than either single release (51.2% +/- 5.8% or 52.5% +/- 8.0%, P < .01). Furthermore, the LDPII in the dual release (94.2% +/- 10.9%) was equivalent to that with 80 microg of bFGF/CM (95.1% +/- 7.6%) alone or 80 microg of HGF/CM (92.8% +/- 7.6%) alone. A histologic evaluation at 4 weeks showed capillary density in the dual release (868 +/- 173 vessels/mm(2)) was higher than that in either single release (204 +/- 68 vessels/mm(2) or 185 +/- 98 vessels/mm(2) , P < .01). The percentage of mature vessels assessed by alpha-smooth muscle actin staining was also higher in the dual release (43.8% +/- 7.8% vs 9.5% +/- 3.0% or 11.7% +/- 3.8%, respectively; P < .01). CONCLUSIONS: This study demonstrates that the sustained dual release of a lower dose of bFGF and HGF from a carrier matrix can achieve equivalent blood perfusion recovery and more mature vasculature in the ischemic limb than a higher dose of bFGF or HGF alone. This approach may be a highly promising strategy for the future treatment of peripheral vascular disease.

Therapeutic angiogenesis by the controlled release of basic fibroblast growth factor for ischemic limb and heart injury: toward safety and minimal invasiveness.

We review our studies on therapeutic angiogenesis using basic fibroblast growth factor (bFGF) released in a controlled manner from biodegradable gelatin hydrogel (GH). The bFGF-GH was intramuscularly injected in rabbits with limb ischemia. The group treated with bFGF showed an increase in tissue blood flow under laser Doppler imaging and histology showed a greater vascular density compared with controls. Also, bFGF-GH was subepicardially injected into old heart infarcts in rats. In the group treated with bFGF, improved left ventricular function was shown by echocardiography and cardiac catheterization, increased regional blood flow in the peri-infarct area was detected by pinhole single-photon emission computed tomography using (201)Tl, and increased vascular density was demonstrated by histology. In rabbits with acute myocardial infarction, the heart was wrapped with the omentum (including the gastroepiploic artery) and a bFGF-GH sheet was applied. Postoperative assessment revealed rich communication from the gastroepiploic artery to the coronary artery and improved cardiac function. The controlled release of bFGF was effective for both limb and heart ischemia and is considered to be suitable for clinical use because its application in animals was feasible and safe with minimal invasiveness.

Development of biologic coronary artery bypass grafting in a rabbit model: revival of a classic concept with modern biotechnology.

OBJECTIVE: We have developed a technique for biologic coronary artery bypass grafting, which is a revival of a classic concept with modern biotechnology. METHODS: Acute myocardial infarction was created by ligating the major branch of the circumflex artery in rabbits. Animals were divided into four groups: a nontreated group (group N), a group in which omentum was used to wrap the infarcted area (group G), a group in which a gelatin hydrogel sheet incorporating 100 microg basic fibroblast growth factor was placed over the infarcted area (group F), and a group in which the infarcted area was similarly treated with basic fibroblast growth factor followed by omental wrapping (group FG). Cardiac function was subsequently assessed by echocardiography. Postmortem angiography through the gastroepiploic artery was done in groups G and FG. Infarct size and arteriolar density were evaluated. RESULTS: Group FG showed a better fractional area change than did the other groups (group N P <.001, group G P =.002, group F P <.001). Angiography revealed that communication from the gastroepiploic artery to the coronary artery was created through a rich bed of neovascularization in all 7 animals of group FG, whereas poor collaterals were recognized in only 2 of 7 animals in group G. Infarct size was reduced to a greater extent in group FG than in groups F, G, and N (10% +/- 3%, 16% +/- 5%, 19% +/- 7%, 23% +/- 2%, respectively, group F P =.04, groups G and N P <.01). The number of arterioles 20 to 100 microm in diameter was increased to a greater extent in group FG than in groups F, G, and N (23 +/- 5 arterioles/mm(2), 14 +/- 3 arterioles/mm(2), 10 +/- 1 arterioles/mm(2), 4 +/- 2 arterioles/mm(2), respectively), with the differences being significant. CONCLUSIONS: These results show that bypass from the gastroepiploic artery to coronary arteries can be achieved without surgical anastomosis through slow release of basic fibroblast growth factor in this rabbit acute myocardial infarction model. This new revascularization concept, biologic coronary artery bypass grafting, could be applicable for revascularizing many tiny coronary vessels in patients who are difficult to treat with conventional surgery or catheter intervention.

Pericardial fluid level of heart-type cytoplasmic fatty acid-binding protein (H-FABP) is an indicator of severe myocardial ischemia.

BACKGROUND: Heart-type cytoplasmic fatty acid-binding protein (H-FABP) has been reported as a sensitive and specific marker for the early diagnosis of acute myocardial infarction. Our hypothesis was that serum or pericardial fluid levels of H-FABP can reflect not only myocardial infarction but also myocardial ischemia. METHODS: A total of 34 patients with unstable angina, who had anginal symptoms and/or ST-changes in ECG monitoring within 24 h before operation, were classified into group A (n=17), and those without these symptoms and changes into group B (n=17). Blood and pericardial fluid samples were obtained immediately after median sternotomy, and serum and pericardial fluid levels of creatine kinase-MB, cardiac troponin-T, and H-FABP were measured. RESULTS: Serum H-FABP levels were slightly elevated compared with their normal values in both groups. While they showed no difference between groups A and B (group A vs. B: 8.5+/-1.0 vs. 7.1+/-0.7 ng/ml, P=0.25), pericardial fluid levels of H-FABP were significantly higher in group A than in group B (16.3+/-2.0 vs. 9.6+/-1.0 ng/ml, P=0.0046). H-FABP showed a weak correlation between its serum levels and pericardial fluid levels (r=0.40). CONCLUSIONS: Pericardial fluid levels of H-FABP reflect myocardial ischemia occurring within 24 h of their measurements. H-FABP may be secreted into the interstitial space by increased permeability of the myocardial cell membrane associated with severe myocardial ischemia. Thus, pericardial fluid reflects pathophysiological conditions of cardiomyocytes more sensitively than circulating blood.

Clinical characteristics relevant to myocardial cell apoptosis: analysis of pericardial fluid.

We investigated the pro-apoptotic potential of pericardial fluids from patients with different clinical conditions on cultured neonatal rat cardiomyocytes. Pericardial fluids were obtained during open heart surgery from 88 patients with ischemic heart disease (n=44), valvular heart disease (n=32), or aortic disease (n=12). The terminal deoxynucleotidyl transfer-mediated end labeling fragmented nuclei assay was performed on primary cardiac myocytes from neonatal rats in the presence of 1% pericardial fluid from each patient. We evaluated relations between these patients' clinical characteristics and the extent of myocardial cell apoptosis. Induction of myocardial cell apoptosis by pericardial fluids was observed in 29 of the 88 patients (33.0%). The prevalence of myocardial cell apoptosis was significantly influenced by diabetes mellitus (DM) (53.6% with vs. 23.3% without, P<0.005), acute coronary syndrome (ACS) (64.7% with vs. 25.4% without, P<0.005), and poor left ventricular systolic function (60.0% with vs. 25.0% without, P<0.005). Multivariate stepwise logistic regression analysis revealed that the presence of DM, ACS, and poor left systolic function were significant predictors of myocardial cell apoptosis. DM, ACS and left ventricular dysfunction may play important roles in the pathogenesis of myocardial cell apoptosis in the clinical setting.

Gelatin sheet incorporating basic fibroblast growth factor enhances sternal healing after harvesting bilateral internal thoracic arteries.

OBJECTIVE: We previously reported that a gelatin sheet incorporating basic fibroblast growth factor accelerated sternal healing after bilateral internal thoracic artery removal in normal and diabetic rats. The aim of this study was to evaluate the effects of this therapeutic modality on sternal healing in a large-animal model before performing a clinical trial. METHODS: After median sternotomy and bilateral internal thoracic artery removal in a pedicled fashion, 14 beagle dogs received either a gelatin sheet incorporating basic fibroblast growth factor (100 mug per sheet) on the posterior table of the sternum (FGF group, n = 7) or did not receive a gelatin sheet (control, n = 7). We compared sternal healing 4 weeks after surgical intervention between the groups. RESULTS: Scintigraphic images obtained by using technetium 99 methylene diphosphonate bone scanning were assessed visually, and the impulse rate was quantified 30 and 60 minutes after injection of technetium 99 methylene diphosphonate to evaluate the sternal perfusion. Sternal uptake was significantly increased in the FGF group (30 minutes: 221% +/- 30% vs 180% +/- 36%; 60 minutes: 267% +/- 26% vs 197% +/- 42%; P <.01). Apparent sternal dehiscence, as assessed radiographically, was observed only in the control animals. Histologically, complete healing of the sternum with marked angiogenesis was observed in the FGF group, whereas poor healing with limited angiogenesis was seen in the control animals. Both bone mineral content (134 +/- 49 vs 52 +/- 32 mg, P <.01) and bone mineral density (133 +/- 53 vs 66 +/- 32 mg/mm(2), P <.05) along the incision line of the sternum, as assessed by means of dual-energy x-ray absorptometry, were higher in the FGF group. CONCLUSIONS: A gelatin sheet incorporating basic fibroblast growth factor enhances sternal perfusion and accelerates sternal bone healing in large animals.23