Improvement of renal dysfunction in a patient with hepatitis C virus‐related liver cirrhosis by daclatasvir and asunaprevir combination therapy: A case report

Recently, treatments for chronic hepatitis C virus (HCV) infection have been drastically improved by the development of direct‐acting antiviral agents. In September 2014, dual oral therapy using daclatasvir (DCV) and asunaprevir (ASV) was approved for the treatment of chronic HCV infection in Japan. We treated a patient with HCV‐related liver cirrhosis with severe leg edema due to chronic renal dysfunction using this dual oral therapy. Although serum alanine aminotransferase increased rapidly during the first week of treatment, the antiviral therapy was able to continue, and liver function recovered spontaneously. After 1 month of treatment, serum HCV RNA became continuously undetectable, and serum albumin level gradually increased. Throughout the therapy, serum creatinine level nearly normalized, and leg edema gradually improved. These improvements continued after the combination therapy was completed. HCV RNA remained undetectable following the end of therapy, and sustained virological response at 12 weeks was achieved. It has been reported that chronic HCV infection is associated with renal dysfunction and that HCV eradication can improve it. DCV and ASV combination therapy is safe for patients who have renal dysfunction and may be a suitable therapy for chronic hepatitis C patients with renal dysfunction.     

Pathological autopsy of a patient that underwent a successful ablation of an electrical storm from the left ventricular summit

A 65-year-old man with non-ischemic cardiomyopathy, underwent an autopsy 2 months after the successful ablation of a sustained left ventricular (LV) summit ventricular tachycardia (VT). The patient died due to interstitial pneumonia from amiodarone use. The earliest activation sites of the VT were documented from both inside the anterior interventricular vein (AIV) and epicardial surface. The diameter of the AIV was 3–4 mm, and the radiofrequency (RF) lesion inside the AIV was a slight lesion due to high impedance with a high temperature. The lesion from the epicardial surface was also superficial and insufficient due to neighboring coronary arteries and the existence of epicardial fat. A successful application was performed from the LV endocardium, and diffuse myocardial fibrosis was observed in the mid-myocardium including inside the RF lesions. The actual relationship between the myocardial fibrosis and LV summit VT remains unclear, but this case showed the difficulty of achieving a successful ablation from the epicardial side, when the focus exists in the mid-myocardium around the LV summit.     

Pro- vs anti-stenotic capacities of type-I vs type-II human induced pluripotent-derived endothelial cells

AIM: To verify in vivo relevance of the categorization of human vascular endothelial cells (VECs) into type-I (pro-proliferative) and type-II (anti-proliferative). METHODS: Endothelial layers of murine femoral arteries were removed by wire injury (WI) operation, a common technique to induce arteriostenosis. Type-I and type-II VECs produced from human induced pluripotent stem cells (iPSCs), whose characters were previously determined by their effects on the proliferation of vascular smooth muscle cells in in vitro co-culture experiments, were mixed with Matrigel^® Matrix. The mixtures were injected into subcutaneous spaces around WI-operated femoral arteries for the transplanted human iPSC-derived VECs (iPSdECs) to take a route to the luminal surface via vasa vasorum, a nutrient microvessel for larger arteries. Histologies of the femoral arteries were examined over time. The presence of human iPSdECs was checked by immunostaining studies using an antibody that specifically recognizes human VECs. Degrees of stenosis of the femoral arteries were calculated after three weeks. To determine the optimal experimental condition, xenotransplantation experiments were performed under various conditions using immunocompromised mice as well as immunocompetent mice with or without administration of immunosuppressants. RESULTS: Because immunocompromised mice showed unexpected resistance to WI-induced arteriostenosis, we performed xenotransplantation experiments using immunocompetent mice along with immunosuppressant administrations. After one week, luminal surfaces of the WI-operated arteries were completely covered by human iPSdECs, showing the efficacy of our novel transplantation technique. After three weeks, type-I-iPSdECs-transplanted arteries underwent total stenosis, while type-II-iPSdECs-transplanted arteries remained intact. However, untransplanted arteries of immunosuppressant-treated mice also remained intact by unknown reasons. We found that transplanted human VECs had already been replaced by murine endothelial cells by this time, indicating that a transient existence of human type-II-iPSdECs on arterial luminal surfaces can sufficiently prevent the development of stenosis. Thus, we re-performed xenotransplantation experiments using immunocompetent mice without administrating immunosuppressants and found that arteriostenosis was accelerated or prevented by transplantation of type-I or type-II iPSdECs, respectively. Similar results were obtained from the experiments using human embryonic stem cell-derived VECs at early passages (i.e., type-II) and late passages (i.e., type-I). CONCLUSION: Pro- and anti-stenosis capacities of type-I and type-II human iPSdECs were verified, respectively, promising a therapeutic application of allogenic iPSdECs.     

Laparoscope-assisted anal sphincter-preserving operation preceded by transanal procedure

BACKGROUND: Transanal intersphincteric resection (ISR) was introduced and has been increasingly performed as an ultimate surgical treatment for extremely low rectal cancer. We considered that high quality and less invasive surgery could be achieved if ISR and laparoscopic surgery were combined. METHODS: Between December 2003 and June 2004, we performed laparoscope-assisted ISR for two patients with very low rectal cancer and total colectomy for two patients with ulcerative colitis complicated by colorectal cancer. In all patients, the transanal procedure was preceded by trans-abdominal laparoscopic rectal excision. RESULTS: Preceding transanal dissection facilitated muscle layer-oriented curative dissection, and more importantly, made subsequent laparoscopic rectal excision effortless as a result of penetrating to the dissected pelvic cavity. All patients showed favorable recovery including postoperative anal function with no complication or recurrent disease. CONCLUSIONS: This procedure is feasible and has favorable short-term results for radical treatment of very low rectal disease, while preserving anal function.     

Sustained progression and loss of the gender-related difference in atherosclerosis in the very old: a pathological study of 1074 consecutive autopsy cases

INTRODUCTION: Epidemiological surveys show decrease or reversal of male predominance in cardiovascular mortality in the very old, but the actual condition of atherosclerosis in the very old is largely unknown. The objective of this paper is to reveal whether the atherosclerosis continues to progress, or the gender-related difference exists in the very old. METHODS: The subjects were 1074 consecutive autopsy cases of in-hospital death. The male:female ratio was 1.1:1 and the average age was 80 years. Macroscopic evaluation was performed on the degree of atherosclerosis in 10 arteries including the intracranial arteries, carotid artery, aorta, coronary artery, and femoral artery. RESULTS: The severity of atherosclerosis differed greatly among arteries. The age-related increase of the atherosclerotic degree was evident, even after 80 years of age. The atherosclerosis was more severe in males than in females in their 60s, but this male predominance decreased with ageing and finally disappeared in their 90s. CONCLUSION: The sustained progression of atherosclerosis and loss of the gender-related difference probably account for the increase of cardiovascular mortality in very old females. They also suggest that the prevention of the atherosclerotic progression is still important in the seventh and eighth decade of life.