IntroductionCell sheets using myoblasts have been developed for the treatment of heart failure after myocardial infarction (MI) bridging to heart transplantation. Stem cells are supposed to be better than myoblasts as a source of cells, since they possess a potential to proliferate and differentiate into cardiomyocytes, and also have capacity to secrete angiogenic factors. Adipose-derived stem cells (ASCs) obtained from fat tissues are expected to be a new cell source for ASC sheet therapies. Administration of angiotensin II receptor blockers (ARBs) is a standard therapy for heart failure after MI. However, it is not known whether ARBs affect the cell sheet therapy. This study aimed to examine ameliorating effects of ASC sheets on heart failure and remodeling after MI, and how pretreatment with ARBs prior to the creation of MI and ASC sheet transplantation modifies the effects of ASC sheets.MethodsASCs were isolated from fat tissues of wild-type rats, and ASC sheets were engineered on temperature-responsive dishes. In in vitro studies using cultured cells, mRNA levels of vascular endothelial growth factor (VEGF) in ASCs were determined by RT-PCR in the presence of angiotensin II and/or an ARB, irbesartan, under normoxia and hypoxia; mRNA and protein levels of angiotensin II receptor type 1a (AT1aR), type 1b (AT1bR) and type 2 (AT2R) were also determined by RT-PCR and western blotting. In in vivo studies using a rat MI model, effects of transplanted ASC sheets and/or irbesartan on cardiac functions and remodeling after MI were evaluated by echocardiography, histological analysis and molecular biological techniques.ResultsIn the in vitro studies, ASCs expressed higher levels of VEGF mRNA under hypoxia. They also expressed mRNA and protein of AT1aR but not AT1bR or AT2R. Under normoxia, angiotensin II increased the level of VEGF mRNA in ASCs, which was abolished by irbesartan. Under hypoxia, irbesartan reduced the level of VEGF mRNA in ASCs regardless of whether angiotensin II was present or not. In the in vivo studies, ASC sheets improved cardiac functions after MI, leading to decreased interstitial fibrosis and increased capillary density in border zones. These effects of ASC sheets were abolished by oral administration of irbesartan before MI and their transplantation.ConclusionsASC sheets ameliorated cardiac dysfunctions and remodeling after MI via increasing VEGF expression, which was abolished by pretreatment with irbesartan before the creation of MI and transplantation.

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Pigmented squamous cell carcinoma is a rare variant of squamous cell carcinoma. We report a case of pigmented squamous cell carcinoma with dermoscopic examination probably arisen from actinic keratosis in a 101-year-old woman who was surgically treated under general anesthesia. In addition, we discuss indications of general anesthesia in elderly patients with skin cancer, differential diagnosis and dermoscopic features of pigmented squamous cell carcinoma.

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Background Although head and neck reconstruction using free flaps has become a common procedure, flap complications remain a concern. This study aimed to analyze the risk factors of free flap complications and to identify the causes of these complications. Methods We studied 97 patients with head and neck cancer with intraoral defects who underwent reconstruction using free flaps at Tottori University Hospital between 2011 and 2020. We used a retrospective cohort study design to investigate whether flap complications, including f lap necrosis (total and partial) and f lap dehiscence, were related to various factors, including the underlying disease condition, treatment status, and surgical factors. Results Of the 97 patients analyzed, total flap necrosis was observed in one patient (1.0%). The incidence rate of flap complications, including flap necrosis and flap dehiscence, was 29.9%. When the time taken to perform one vascular anastomosis, including preparation of the recipient vessel and flap vessel, exceeded 30 min, the incidence rates of flap necrosis (total and partial) (odds ratio, 8.30; 95% confidence interval, 1.91-36.00; P = 0.005) and flap dehiscence (odds ratio, 3.46; 95% confidence interval, 1.05-11.36; P = 0.041) increased significantly. ConclusionThe time taken to perform one vessel anastomosis was the factor that contributed the most to the incidence of flap complications. Reconstructive surgeons should reduce the incidence of flap complications by keeping the known risk factors of the surgery in mind and by aiming to complete a vascular anastomosis time, including the time taken for the preparation of vessels, of ≤ 30 min per vessel during surgery.