Mucosal adjuvanticity and mucosal booster effect of colibactin-depleted probiotic Escherichia coli membrane vesicles.

There is a growing interest in development of novel vaccines against respiratory tract infections, due to COVID-19 pandemic. Here, we examined mucosal adjuvanticity and the mucosal booster effect of membrane vesicles (MVs) of a novel probiotic E. coli derivative lacking both flagella and potentially carcinogenic colibactin (ΔflhDΔclbP). ΔflhDΔclbP-derived MVs showed rather strong mucosal adjuvanticity as compared to those of a single flagellar mutant strain (ΔflhD-MVs). In addition, glycoengineered ΔflhDΔclbP-MVs displaying serotype-14 pneumococcal capsular polysaccharide (CPS14+MVs) were well-characterized based on biological and physicochemical parameters. Subcutaneous (SC) and intranasal (IN) booster effects of CPS14+MVs on systemic and mucosal immunity were evaluated in mice that have already been subcutaneously prime-immunized with the same MVs. With a two-dose regimen, an IN boost (SC-IN) elicited stronger IgA responses than homologous prime-boost immunization (SC-SC). With a three-dose regimen, serum IgG levels were comparable among all tested regimens. Homologous immunization (SC-SC-SC) elicited the highest IgM responses among all regimens tested, whereas SC-SC-SC failed to elicit IgA responses in blood and saliva. Furthermore, serum IgA and salivary SIgA levels were increased with an increased number of IN doses administrated. Notably, SC-IN-IN induced not only robust IgG response, but also the highest IgA response in both serum and saliva among the groups. The present findings suggest the potential of a heterologous three-dose administration for building both systemic and mucosal immunity, e.g. an SC-IN-IN vaccine regimen could be beneficial. Another important observation was abundant packaging of colibactin in MVs, suggesting increased applicability of ΔflhDΔclbP-MVs in the context of vaccine safety.

Association between Hospital-acquired Disability and Clinical Outcomes in Older Patients Who Underwent Cardiac Surgical.

OBJECTIVE: This study aimed to clarify the association between hospital-acquired disability (HAD) and prognosis in older patients who underwent cardiac surgery. METHODS: This single-center, retrospective, observational study included 141 patients aged ≥65 years who underwent cardiac surgery at our hospital from November 2016 to August 2021. The primary endpoint of this study was the occurrence of major adverse cardiac and cerebrovascular events (MACCEs) within 2 years of hospital discharge. HAD was defined as a score of ≤5 on any one of the functional independence measure (FIM) subitems at discharge compared to preoperatively. RESULTS: MACCE was observed in 16.3%, and the incidence of MACCE was significantly higher in the HAD group than that in the non-HAD group (12.1 vs. 34.5%, log-rank, p = 0.003). HAD was also significantly associated with the MACCE (hazard ratio [HD]: 2.575, 95% confidence interval [CI]: 1.001-9.655, p = 0.046). The incidence rate of HAD was 20.6%, with age (odds ratio [OR]: 1.260, 95% CI: 1.080-1.470, p = 0.004), preoperative short physical performance battery (SPPB) score (OR: 0.462, 95% CI: 0.301-0.708, p <0.001), and postoperative delirium (OR: 6.660, 95% CI: 1.480-30.000, p = 0.014) identified as significant factors. CONCLUSION: HAD is an independent predictor of MACCE in older patients who underwent cardiac surgery.

Iliofemoral Aneurysm in Patients with Type 1 Neurofibromatosis: A Case Report and a Literature Review.

Vascular involvement, especially in the iliofemoral segment, is rare in type 1 neurofibromatosis. We herein report a case involving a 49-year-old male diagnosed with type 1 neurofibromatosis who presented with right inguinal pain and swelling. CT angiography revealed a 50-mm aneurysm extending from the right external artery to the common femoral artery. Although surgical reconstruction was performed successfully, the patient required an additional operation 6 years later for aneurysm enlargement in the deep femoral artery. Histopathological examination confirmed the proliferation of neurofibromatosis cells in the aneurysm wall.

[Pulmonary Adenocarcinoma in Situ with Positive Findings in Pleural Lavage Cytology].

We report a rare case of positive findings in pleural lavage cytology(PLC) in the patient with pulmonary adenocarcinoma in situ (AIS). A 78-year-old woman was presented with a 30 mm pure groundglass nodule (GGN) in the left upper lobe on chest computed tomography (CT). After 2 years follow- up, thoracoscopic surgery was performed to resect the nodule. PLC was performed before pulmonary resection. Histopathological diagnosis was 25 mm AIS. However, PLC showed positive findings of malignant cells. CT examination at 1 year and 6 months postoperatively showed pleural dissemination findings and the patient died of lung cancer at 3 years and 2 months postoperatively. PLC's contribution to TNM staging has not yet been clarified. The positive findings in PLC and large size of pure GGN were considered likely to be poor prognostic indicators.

A Case of Severe Aortic Stenosis after Aortic Valve Neocuspidization Using Autologous Pericardium (Ozaki Procedure).

A 56-year-old man with a history of left nephrectomy for Wilms' tumor on chronic hemodialysis underwent aortic valve neocuspidization using autologous pericardium (Ozaki procedure) for aortic stenosis (AS) due to a bicuspid aortic valve 6 years ago. The AS gradually progressed and a decrease in the left ventricular ejection fraction was observed. Because of this, we decided to perform reoperative aortic valve replacement using a mechanical valve. Intraoperative findings showed severe calcification at the site where the autologous pericardium was sutured to the annulus. However, the degeneration of the valve leaflets themselves was mild. While excellent mid-term results have been reported for the Ozaki procedure, the long-term results are still unclear. In this case, the annulus was severely calcified, which reduced the mobility of the leaflet. We report the first case of AS progression requiring reoperation in the long-term period after the Ozaki procedure.

[Simultaneous Resection of Mediastinal and Liver Hydatid Disease].

Cystic echinococcosis is an uncommon zoonosis in Japan. Typical location of the cyst is the liver and the lung. Mediastinal hydatidosis is found in less than 0.1% of all hydatid disease patients. We report a rare case of 68 years old male with mediastinal and liver hydatid cysts. Serological test confirmed the diagnosis of hydatidosis. The patient underwent complete resection of mediastinal and liver cysts successfully. Postoperative follow-up for two years has not shown any signs of recurrence. Simultaneous resection of the cysts in different sites including mediastinum is rare and has not been reported in Japan. Hydatid disease is an important differential diagnosis for patient who has cryptogenic liver cyst and history of contact to wildlife or unsterile water.

Morphological changes of the tricuspid valve complex in functional tricuspid regurgitation on contrast-enhanced computed tomography.

BACKGROUND: Whether it is possible to perform morphological evaluation of functional tricuspid regurgitation (FTR) on contrast-enhanced computed tomography (CT) was examined by evaluating the relationships between the parameters measured on contrast-enhanced CT and TR severity on transthoracic echocardiography. METHODS: Fifty patients underwent contrast-enhanced CT. Tricuspid annulus area (TAA), tricuspid annulus circumference (TAC), right ventricular volume (RVV), and the distances between the tips and bases of the papillary muscles were measured on contrast-enhanced CT in diastole and systole. The 50 cases were divided into 34 in the TR ≤ mild group (no TR: 3 cases, trivial TR: 24 cases, mild TR: 7 cases), and 16 in the TR ≥ moderate group (moderate TR: 8 cases, severe TR: 8 cases) using the TR grade measured by transthoracic echocardiography, and then differences between the groups were examined. RESULTS: Significant differences were found in TAA, TAC, and RVV (p < 0.01) and the distances between the tips of the anterior and posterior papillary muscles (p < 0.05) in both diastole and systole. Since the septal papillary muscle could not be identified in 18 cases (36.0%), only the distance between the anterior and posterior papillary muscles was measurable in all cases. On receiver-operating characteristic (ROC) curve analysis, the areas under the ROC curves (AUCs) of TAA, TAC, and RVV were all > 0.7, and the maximum AUC was 0.925 for dRVV. CONCLUSIONS: TAA, TAC, RVV, and the distance between the tips of the anterior and posterior papillary muscles measured on contrast-enhanced CT were shown to be significantly increased in the TR ≥ moderate group. Detailed morphological assessment of FTR is possible by contrast-enhanced CT.

Efficacy of intravenous propranolol for life-threatening diffuse neonatal hemangiomatosis.

Oral propranolol is recommended as the first-line agent for infantile hemangioma requiring systemic treatment. Life-threatening complications such as obstructive infantile hemangioma of the airway or infantile hepatic hemangioma associated with high-output congestive heart failure are major indications for the consideration of early treatment. We present the case of an infant with life-threatening diffuse neonatal hemangiomatosis, including airway obstruction due to subglottic hemangioma, heart failure due to multiple hepatic hemangiomas with portohepatic venous shunts, and severe anemia due to continuous gastrointestinal bleeding, in which treatment with intravenous propranolol proved successful.

Case Report: Structural Changes in the Coronary Vessel Wall in a Patient With Incomplete Kawasaki Disease.

Background: Kawasaki disease (KD) is an acute systemic vasculitis of infants and young children that affects medium-sized vessels. Conventional cardiac imaging techniques, such as cardiac catheterization, are useful for characterizing the coronary arterial lesion (CAL) size and luminal diameter of the diseased coronary artery segment in patients with KD, but there are limitations to the visualization of the detailed vascular anatomy. Optical coherence tomography (OCT) is a high-resolution intracoronary arterial imaging modality that can distinguish the three layers of the coronary arterial wall. Several studies have reported coronary artery wall abnormalities in KD patients with coronary arterial aneurysm or regressed aneurysm. However, there have been no reports on changes in the coronary artery wall in cases of incomplete KD without CAL. Case Presentation: We herein report an 11-year-old girl with a history of incomplete KD without coronary arterial aneurysms. She had been diagnosed with perimembranous ventricular septal defect (VSD) after birth and had experienced incomplete KD at 1 year old. During her hospitalization for KD, she did not receive intravenous immunoglobulin (IVIG), because she did not meet the Harada score or criteria for treatment in patients with incomplete KD established by the American Heart Association. No dilatation or coronary artery aneurysm were observed on transthoracic echocardiography in the acute or follow-up period. At 11 years old, she received cardiac catheterization and coronary angiography (CAG) for the evaluation of a VSD and follow-up of KD. CAG demonstrated no aneurysm, dilatation, or significant stenosis of the coronary arteries. We performed an OCT study, which revealed the presence of intimal thickening, disruption of the media, and neovascularization in the left anterior descending artery. Conclusion: OCT demonstrates the structural changes of CA even in the patient with incomplete KD who have not been treated with IVIG.

Multiple Transport Mechanisms Involved in the Intestinal Absorption of Metformin: Impact on the Nonlinear Absorption Kinetics.

The aim of this study was to investigate the contributions of multiple transport mechanisms to the intestinal absorption of metformin, focusing on OCT3, PMAT, THTR2, SERT and OCTN2. We also assessed the impact of these transporters on the nonlinear absorption of metformin. Uptake studies with MDCKII cells expressing OCT3, PMAT, THTR2 or SERT confirmed that metformin is a substrate of these transporters. Decynium22 strongly inhibited metformin uptake mediated by all the transporters. 7-Cyclopentyl inhibited OCT3- and THTR2-mediated uptake of metformin. AG835, thiamine and paroxetine specifically inhibited PMAT-, THTR2- and SERT-mediated uptake of metformin, respectively. Using these inhibitors, the relative contributions of OCT3, PMAT, THTR2, SERT, OCTN2 and others to the intestinal permeation of metformin across Caco-2 cells were estimated to be 9.77%, 9.68%, 22.2%, 1.52%, 0% and 0.66%, respectively. Concentration-dependent analysis of metformin uptake by Caco-2 cells revealed nonlinear kinetics with the similar Km(app) value to the value for THTR2. Further in situ absorption study demonstrated that rat intestinal permeability of metformin was significantly decreased in the presence of decynium22, 7-cyclopentyl and thiamine. The present study indicated that THTR2 is the major determinant of the nonlinear absorption of metformin, although multiple transport mechanisms contribute to its intestinal absorption.

[Coronary Aneurysm with Fistula].

We successfully treated two rare cases of coronary aneurysm with fistula. Case 1;A 65-year-old female referred to our hospital with the coronary aneurysm and fistula. Right coronary aneurysm with fistula leading to coronary sinus was observed. Coronary bypass surgery using a saphenous vein to #4PD was performed, and two right ventricle branches were reconstructed. Coronary aneurysm was resected. Case 2;A 46-year-old male was admitted with chest discomfort. Coronary aneurysm with fistula from the left main trunk to left ventricle was demonstrated. Ligation of the coronary artery aneurysm and suture closure of the entry site to the left ventricle was performed. Both patients had uneventful recovery.

[Third Tricuspid Valve Replacement:Report of a Case].

A 79-year-old man underwent tricuspid valve replacement (TVR) with a bovine pericardial bioprosthesis, Carpentier-Edwards Perimount (CEP), for tricuspid regurgitation 27 years earlier. Twenty-one years after the first operation, he underwent re-TVR with a bovine pericardial bioprosthesis, Magna Mitral Ease, due to prosthetic valve dysfunction. Since the prosthetic valve dysfunction progressed again, the third TVR was performed six years after the second operation. The findings of the resected bioprosthesis showed sclerosis of the septal cusp, and pannus formation between the septal and posterior cusps. For the third TVR, the porcine bioprosthesis Epic was used. Neither transvalvular nor perivalvular leakage was observed postoperatively, and the patient was discharged without any complications.

[Penetrating Right Ventricular Injury by Suicide Attempt:Report of a Case].

Penetrating heart injury is rare in Japan. A 35-year-old man stabbed himself with a fruit knife that was about 10 cm in length on the left precordium in an attempt to commit suicide and was transferred to our hospital. His vital signs were stable, and the knife remained stabbed in the left precordium. Cardiac injury and cardiac tamponade were suspected on computed tomography, and emergency surgery was performed. A large amount of red hematoma was found in the mediastinum and the pericardial space after median sternotomy. The knife had created a fissure of about 15 mm in the free wall of the right ventricle, and the injury was repairable. The knife passed through the sixth costal cartilage and the left internal thoracic artery, and hemostasis was easy. The patient's postoperative course was uneventful, but due to the suicide attempt and adjustment disorder, the patient was transferred to a psychiatric hospital on postoperative day 10.

Case Report: Disappearance of Coronary Anastomotic Aneurysm by Steroid Therapy in Takayasu Arteritis: Pseudorepair of Pseudoaneurysm?

Background: Takayasu arteritis (TA) is a large vessel vasculitis of unknown etiology characterized by chronic inflammatory changes of the aorta and its major branches. Complications such as anastomotic aneurysm and valve detachment have been reported in active TA patients who received aortic valve replacement and graft replacement of aorta. Case Summary:A 61-year-old man with a history of emergency aortic valve replacement and patch closure of the noncoronary sinus of Valsalva due to acute heart failure induced by acute aortic regurgitation and ruptured sinus of Valsalva 4 years ago was referred for exertional dyspnea. Dilatation of the sinus of Valsalva together with protrusion of the right sinus of Valsalva and ostial stenosis of the left coronary artery were newly found by computed tomography (CT). A Bentall operation with concomitant coronary artery bypass grafting was successfully performed with a composite graft. Diagnosis of TA was made on the basis of histological analyses of the resected sinus of Valsalva, though other arterial manifestations were not detected by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography. Three months later, a follow-up study revealed left coronary ostial pseudoaneurysm at the anastomotic site together with strong 18F-FDG uptake, leading to commencement of steroid therapy. Eight months later, disappearance of left coronary ostial pseudoaneurysm was found by a follow-up CT scan. Conclusion: This is a rare TA case in whom spontaneous resolution of coronary anastomotic aneurysm by steroid therapy was found without reconstructive surgery.

[Papillary Fibroelastoma Arising from the Left Atrial Wall:Report of a Case].

Papillary fibroelastoma (PFE) is a rare benign cardiac tumor generally arising from the valvular endocardium. We report an extremely rare case of PFE arising from the left atrial wall. A 70-year-old male patient was admitted to our hospital with a diagnosis of left atrial tumor. Echocardiography and enhanced computed tomography showed an approximately 14 mm mass on the left atrial wall. Moreover, the magnetic resonance imaging showed hyperintenseness on a T2-weighted image. We diagnosed the tumor as a myxoma. Intraoperatively, we found a mobile tumor on the left atrial wall. It had a sea anemone-like appearance and was suspected to be PFE. We performed the tumor resection including the left atrial wall. Histological examination confirmed PFE. His postoperative course was uneventful.

Open sandwich fluorescence-linked immunosorbent assay for detection of soy isoflavone glycosides.

To detect major soy isoflavone glycosides, namely daidzin (DZ) and genistin (GEN), novel open sandwich fluorescence-linked immunosorbent assay (os-FLISA) was developed by taking advantage of enhanced interactions between variable regions of heavy (VH) and light chain (VL) domains in the presence of an antigen. The VH and VL genes were expressed in Escherichia coli as a chimera protein with green fluorescence protein (AcGFP1) and maltose-binding protein (MBP), respectively. Comprehensive characterization of os-FLISA displayed nearly the same specificity as parental DZ- and GEN-specific monoclonal antibody, demonstrating the potential of the developed assay for detection of both DZ and GEN. Their detectable range in this system exhibited at 0.1-12.5 µg mL-1. Subsequent validation analysis revealed that os-FLISA was reliable and accurate system for detection of total soy isoflavone glycosides. Notably, this is the first FLISA based on an open sandwich system, which can be employed for the detection of small molecules.

Successful Endovascular Repair of an Abdominal Aortic Aneurysm in a Patient with a Horseshoe Kidney and Accessory Renal Arteries Using an Aortic Cuff to Prevent Type II Endoleak.

A 78-year-old man presented with an abdominal aortic aneurysm (AAA) and a horseshoe kidney coexisting with accessory renal arteries. We performed surgical treatment with endovascular aneurysm repair, sacrificing the accessory renal arteries. We used an aortic cuff to prevent a type II endoleak from the inferior mesenteric and accessory renal arteries. Decreased renal function was transient, and postoperative computed tomography showed no endoleak. This case report supports the feasibility of endovascular surgery for treating AAA in patients with a horseshoe kidney.

Hemodynamic changes in neonates born to mothers with Graves' disease.

PURPOSE: Cardiac insufficiency is a major morbidity in neonatal hyperthyroidism. It is important to assess the hemodynamics in neonates born to mothers with Graves' disease (GD). This study prospectively evaluated the hemodynamic changes in neonates born to mothers with GD. METHODS: Overall, 80 newborns were enrolled. Thirty-six neonates were born to mothers with GD who were positive for thyroid-stimulating hormone (TSH) receptor antibody (TRAb), and 44 were born to mother negative for TRAb. The serum levels of TSH, free triiodothyronine (FT3), free thyroxine (FT4), and N-terminal-pro-B-type natriuretic peptide (NT-proBNP), the cardiac output, and cardiac index (CI) evaluated by echocardiography were compared between the two groups at several postnatal points (day of delivery and 5, 10, and 30 days of life). RESULTS: The TRAb-positive newborns had higher FT4 levels and CI on Day 5 (both p < 0.05) and higher FT3 (p < 0.05) and FT4 levels (p < 0.01) and CI (p < 0.01) but lower TSH levels (p < 0.05) on Day 10 than the TRAb-negative newborns. The TRAb-positive newborns had significantly higher NT-proBNP levels on Days 5 (median 752 vs. 563 pg/mL, p = 0.034) and 10 (median 789 vs. 552 pg/mL, p = 0.002) than the TRAb-negative newborns. CONCLUSIONS: Hemodynamic changes in neonates born to TRAb-positive mothers with GD resulted in a higher CI and NT-proBNP levels than in those with TRAb-negative mothers from postnatal days 5 to 10.

The association between congenital heart disease and small for gestational age with regard to the prevalence and outcomes.

AIM: To evaluate the association between small for gestational age (SGA) and the prevalence of congenital heart disease (CHD) and the association of the SGA status with the outcomes among infants with CHD. METHODS: Echocardiography was performed within the first 5 days of life in 5664 consecutive infants. Infants were classified into four groups according to the presence or absence of SGA and CHD. All CHD infants were followed up until either spontaneous resolution of all cardiac lesions, invasive intervention or death. All newborns without CHD were followed for mortality until the final follow-up date. RESULTS: A total of 303 infants were diagnosed with CHD, while 610 were diagnosed with SGA. Among the CHD infants, 56 were SGA, and 247 were not. A multivariable logistic regression analysis showed that the adjusted odds ratio of SGA (9.71, P < .001) was significantly higher than that of other parameters concerning predictors of invasive intervention or death. The mortality rate in the presence of both SGA and CHD (hazard ratio: 33.6, P < .001) was markedly higher than in the absence of both. CONCLUSION: SGA was a significant predictor of invasive intervention for CHD. The combination of CHD and SGA carried a high risk of death beyond that of either alone.

A rare case of pseudoaneurysm at the site of untreated coarctation of the aorta in an adult patient.

Here we report a rare case of pseudoaneurysm at the site of aortic coarctation. Aortic coarctation and a saccular aortic aneurysm protruding from the site of this coarctation were detected in a 50-year-old woman. Owing to the shape of the aneurysm and high risk of rupture, an open surgical repair was performed. The pathological findings of the removed aneurysm revealed a pseudoaneurysm consisting of only a thin adventitial wall. Adult uncorrected aortic coarctation has a poor prognosis. One of its causes may be the formation of such a pseudoaneurysm.