Anastomotic aneurysms present as a life-threatening emergency after descending aortic replacement for aortic dissection. Thoracic endovascular aneurysm repair (TEVAR) has been performed since the ...early 2000s for complicated cases in which re-thoracotomy cannot be adopted. We report the case of a 57-year-old male patient, during a 5-year follow-up after descending aortic replacement for aortic dissection, developed aneurysm expansion around the false lumen on the peripheral side of the artificial graft. Considering the risk and the patient's desires, we opted to perform TEVAR with different calibers into the true and false lumens "modified kissing stents technique". His postoperative course was uneventful without any complications. This case highlights the utility of the modified kissing stents technique for anastomotic aneurysms after descending aortic replacement for aortic dissection using stent grafts with different calibers into the true and false lumens.
Fulminant myocarditis (FM) is a form of severe inflammatory carditis with rapidly developing acute heart failure.
We report three cases of successful intensive treatment by Impella of FM without any ...complications. In all cases, impairment of microcirculation as measured by blood lactate level and the hemodynamic value as indicated by cardiac index were improved within 24-48 h and 7 days after Impella implantation, respectively. Interestingly, our data also suggested that treatment by Impella CP or 5.0 may lead to faster recovery of microcirculation and cardiac function than treatment by Impella 2.5.
Our findings demonstrate that the appropriate selection of Impella devices guided by body surface area measurements may help to improve clinical outcomes of severe heart failure including FM.
Pancreatic invasive ductal adenocarcinoma (PDAC) has a poor prognosis, and the detection of PDAC during the early stage is thought to improve prognosis. In this study, we retrospectively investigated ...pancreatic morphological abnormalities that lead to the early diagnosis of PDAC with computed tomography (CT) imaging. In total, 41 out of 308 patients diagnosed with pancreatic cancer between 2011 and 2017 in our institution were enrolled. As a control group for the group with pancreatic cancer, 4277 patients without pancreato-biliary diseases were enrolled. We retrospectively reviewed and analyzed the clinical data including patient characteristics, the clinical course and preoperative CT imaging with pancreatic morphological features. Out of 41 patients, 24 patients (58.5%) showed local K-shaped constriction of the pancreatic parenchyma “K-sign” on preoperative CT images. Eight patients (19.5%) showed localized fatty change. Out of 4277 control patients, seven patients (0.16%) showed K-sign. “K-sign” may be used for the early diagnosis of PDAC by CT imaging.
•We investigated the efficacy of cardiac graft function using echocardiography in a murine cardiac allograft transplant model.•The evaluation of cardiac allograft function may be evaluable and ...feasible by using echocardiography.•Left heart function evaluations may be useful from the viewpoint of whether time-course rejection can be evaluated.
Generally, graft function in the murine cardiac allograft transplant model is assessed daily by palpating the heart for evidence of contraction. To our knowledge, few reports have investigated the correlation of cardiac graft function using echocardiography and immunohistochemical studies. In this study, we investigated the efficacy of echocardiographic and histologic evaluation of alloimmune responses in the acute phase of murine cardiac allografts.
Fully vascularized heterotopic hearts from CBA (allogeneic group) or C57BL/6 (syngeneic group) donors were transplanted into C57BL/6 recipients using microsurgical techniques. Fluctuations in heart rate, left ventricular ejection fraction (LVEF), left ventricular functional shortening (LVFS), right ventricular outflow tract maximal systolic velocity (RVOT Vmax), and RVOT velocity time integral (RVOT VTI) were evaluated on postoperative days (PODs) 1, 3, 5, 7, and 9 after transplantation using an ultrasonic device. Histologic studies were also performed.
The syngeneic group did not show a complete cessation of heartbeat or deterioration of cardiac function. CBA recipients in the allogeneic group rejected cardiac allografts on POD 9 after grafting. LVEF and LVFS in the allogeneic group gradually decreased on POD 9. Consistent with the time-course echocardiographic evaluation, histologic studies showed gradual atrophy of the left ventricle. In contrast, RVOT Vmax and RVOT VTI in the allogeneic group were not significantly different during the observation period. Additionally, the thickness of the right ventricular wall did not change until POD 7.
The present findings suggested that echocardiography may help to evaluate time-course murine cardiac graft function through left ventricular parameters such as LVEF and LVFS.
•We investigated the effects of each domain in recombinant human soluble thrombomodulin on alloimmune responses and graft protection.•D1 induced the greatest prolongation of cardiac allografts.•D1 ...promoted regulatory T cells and protected myocardial tissue.
Thrombomodulin is used to manage disseminated intravascular coagulation. In our murine heart transplantation model, the administration of recombinant human soluble thrombomodulin (rTM) could induce the prolongation of cardiac allograft survival. However, there are limited data on the graft protective effects of each r domain (D1, D2, and D3). In this study, we investigated the effects of each domain of rTM on alloimmune responses in a murine model of cardiac allograft transplantation. Fully vascularized heterotopic hearts from C57BL/6 donors were transplanted into CBA recipients using microsurgical techniques. CBA mice that underwent transplantation of C57BL/6 cardiac allografts were assigned to 4 groups: no treatment and each domain-exposed group. The dosage of each domain was determined based on our previous experiments. Flow cytometry and histologic studies were performed to determine whether Foxp3+ regulatory T cells were generated. Untreated and D2-exposed CBA recipients acutely rejected C57BL/6 cardiac allografts within 9 days. Administration of D3 resulted in modest prolongation of allograft survival, and administration of D1 significantly prolonged allograft survival. Histologic studies showed that myocardial damage of allografts from D1- and D3-exposed CBA recipients was controlled compared with that of untreated recipients. In particular, the CD4+CD25+Foxp3+ cell population in the splenocytes of D1-exposed CBA recipients was increased. In conclusion, D1 in rTM could help prolong cardiac allograft survival through regulatory T cell induction and graft protective effects.
Abstract Background We previously demonstrated that the hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (statins) play an important role in the regulation of alloimmune responses. However, ...little is known regarding the effects of statin on allograft protection or donor-specific antibodies (DSA). In this study, we investigated the graft-protective and immunomodulatory effects of rosuvastatin in a model of fully major histocompatibility complex-mismatched murine cardiac allograft transplantation. Methods CBA mice underwent transplantation of C57BL/6 (B6) hearts and received 50 and 500 μg/kg/day of rosuvastatin from the day of transplantation until seven days after the completion of transplantation. To confirm the requirement for regulatory T cells (Tregs), we administered an anti-interleukin-2 receptor alpha antibody (PC-61) to rosuvastatin-treated CBA recipients. Additionally, histological and fluorescent staining, cell proliferation analysis, flow cytometry, and DSA measurements were performed. Results CBA recipients with no treatment rejected B6 cardiac graft acutely (median survival time MST, 7 days). CBA mice treated with 500 μg/kg/day of rosuvastatin prolonged allograft survival (MSTs, 77 days). Fluorescent staining studies showed that rosuvastatin-treated recipients had strong aggregation of CD4 + Foxp3 + cells in the myocardium and around the coronary arteries of cardiac allografts two weeks after grafting. Flow cytometry studies performed two weeks after transplantation showed an increased number of splenic CD4 + CD25 + Foxp3 + T cells in rosuvastatin-treated recipients. The addition of rosuvastatin to mixed leukocyte cultures suppressed cell proliferation by increasing the number of CD4 + CD25 + Foxp3 + Tregs. Additionally, Tregs suppressed DSA production in rosuvastatin-treated recipients. Conclusion Rosuvastatin treatment may be a complementary graft-protective strategy for suppressing DSA production in the acute phase, driven by the promotion of splenic and graft-infiltrating CD4 + CD25 + Foxp3 + Tregs.
Humanized immune system (HIS) mouse models are useful tools for the
investigation of human hematopoiesis. However, the majority of HIS models currently in use are biased towards lymphocyte ...development and fail to support long-term multilineage leucocytes and erythrocytes. Those that achieve successful multilineage reconstitution often require preconditioning steps which are expensive, cause animal morbidity, are technically demanding, and poorly reproducible. In this study, we address this challenge by using HSPC-NBSGW mice, in which NOD,B6.SCID IL-2r
Kit
(NBSGW) mice are engrafted with human CD133
hematopoietic stem and progenitor cells (HSPCs) without the need for preconditioning by sublethal irradiation. These HSPCs are enriched in long-term hematopoietic stem cells (LT-HSCs), while NBSGW mice are permissive to human hematopoietic stem cell (HSC) engraftment, thus reducing the cell number required for successful HIS development. B cells reconstitute with the greatest efficiency, including mature B cells capable of class-switching following allogeneic stimulation and, within lymphoid organs and peripheral blood, T cells at a spectrum of stages of maturation. In the thymus, human thymocytes are identified at all major stages of development. Phenotypically distinct subsets of myeloid cells, including dendritic cells and mature monocytes, engraft to a variable degree in the bone marrow and spleen, and circulate in peripheral blood. Finally, we observe human erythrocytes which persist in the periphery at high levels following macrophage clearance. The HSPC-NBSGW model therefore provides a useful platform for the study of human hematological and immunological processes and pathologies.
Physiological effects of cellular hypoxia are sensed by prolyl hydroxylase (PHD) enzymes which regulate HIFs. Genetic interventions on HIF/PHD pathways reveal multiple phenotypes that extend the ...known biology of hypoxia. Recent studies unexpectedly implicate HIF in aspects of multiple immune and inflammatory pathways. However such studies are often limited by systemic lethal effects and/or use tissue-specific recombination systems, which are inherently irreversible, un-physiologically restricted and difficult to time. To study these processes better we developed recombinant mice which express tetracycline-regulated shRNAs broadly targeting the main components of the HIF/PHD pathway, permitting timed bi-directional intervention. We have shown that stabilization of HIF levels in adult mice through PHD2 enzyme silencing by RNA interference, or inducible recombination of floxed alleles, results in multi-lineage leukocytosis and features of autoimmunity. This phenotype was rapidly normalized on re-establishment of the hypoxia-sensing machinery when shRNA expression was discontinued. In both situations these effects were mediated principally through the Hif2a isoform. Assessment of cells bearing regulatory T cell markers from these mice revealed defective function and pro-inflammatory effects in vivo. We believe our findings have shown a new role for the PHD2/Hif2a couple in the reversible regulation of T cell and immune activity.
Cardiac papillary fibroelastoma (PFE) is a rare tumor, and especially rare when found on the pulmonary valve.
We report the case of a 70-year-old woman patient with a pulmonary valve PFE diagnosed ...incidentally during a follow-up of aortic regurgitation. Computed tomography and magnetic resonance imaging showed no suggestive signs of malignant tumors, and thrombus or myxoma was initially suspected. However, an initial transthoracic and transesophageal echocardiogram did not exclude the possibility of a malignant tumor attached to the wall of the pulmonary artery. Considering the embolization risk, we opted to perform tumorectomy, in which additional surgical procedures could then be conducted if intraoperative diagnosis showed a malignant tumor. Indeed, intraoperative findings showed the tumoral mass attached on the left semilunar cusp of the pulmonary valve, and intraoperative diagnosis of the tumor showed no malignancy. Planned tumorectomy was performed concomitantly with AVR. The pathologic examination of the removed tumor confirmed the diagnosis of PFE. Her postoperative course was uneventful without any sign of recurrence.
This case highlights the difficulty of accurate diagnostic imaging and provides valuable insight into a successful surgical treatment of pulmonary valve PFE without any complications.
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