Intraprocedural Thrombotic Events during Percutaneous Coronary Intervention Due to Acquired Antithrombin Deficiency-related Heparin Resistance Successfully Treated with Antithrombin Gamma Supplementation.

A 75-year-old man receiving treatment for necrotizing pancreatitis developed septic disseminated intravascular coagulation and acute coronary syndrome (ACS). During percutaneous coronary intervention (PCI), a large amount of fresh thrombi appeared after balloon dilatation for the ACS-culprit lesion. Given the low plasma antithrombin (AT) activity and poorly prolonged activated clotting time (ACT), we suspected that acquired AT deficiency-related heparin resistance (HR) was responsible for the thrombus formation. Administration of AT gamma markedly improved ACT, and we successfully completed PCI. We suggest that AT gamma be considered a treatment option for AT deficiency-related HR and subsequent intraprocedural thrombotic events.

Double-Stranded Structure of the Polyinosinic-Polycytidylic Acid Molecule to Elicit TLR3 Signaling and Adjuvant Activity in Murine Intranasal A(H1N1)pdm09 Influenza Vaccination.

Polyinosinic-polycytidylic acid (PIC) is a potent double-stranded RNA (dsRNA) adjuvant useful in intranasal influenza vaccination. In mice, the intensity and duration of immune responses to PIC correlated with the double-stranded chain length. A rational method to avoid PIC chain extension in PIC production is to use multiple short poly(I) molecules and one long poly(C) molecule for PIC assembly. In this study, we elucidate that a newly developed uPIC100-400 molecule comprising multiple 0.1 kb poly(I) molecules and one 0.4 kb poly(C) molecule effectively enhanced the immune responses in mice, by preventing the challenged viral propagation and inducing hemagglutinin-specific IgA, after intranasal A(H1N1)pdm09 influenza vaccination. Reduced intraperitoneal toxicity of PIC prepared with multiple short poly(I) molecules in mice indicates the widened effective range of uPIC100-400 as an adjuvant. In contrast to uPIC100-400, the PIC molecule comprising multiple 0.05 kb poly(I) molecules failed to elicit mouse mucosal immunity. These results were consistent with TLR3 response but not retinoic acid inducible gene I (RIG-I)-like receptor response in the cell assays, which suggests that the adjuvant effect of PIC in mouse intranasal immunization depends on TLR3 signaling. In conclusion, the double-stranded PIC with reduced toxicity developed in this study would contribute to the development of PIC-adjuvanted vaccines.

Clot regression effects of rivaroxaban in the treatment of venous thromboembolism in patients with cancer (CRERIT-VTE cancer): study protocol.

INTRODUCTION: Anticoagulant therapy in patients with cancer with venous thromboembolism (VTE) increases the risk of both VTE recurrence and haemorrhagic complication. Direct oral anticoagulants (DOACs) have been shown to be effective in preventing VTE recurrence, and comparable to conventional therapy in preventing VTE recurrence in patients with advanced cancer. Rivaroxaban is a DOAC that causes thrombus regression, possibly through a profibrinolytic effect. Thrombus regression with initial treatment is essential for VTE patients. However, the thrombolytic effect of DOAC for VTE patients with cancer has not been fully examined. Therefore, in this study, we investigate the thrombolytic effect of rivaroxaban in patients with cancer who develop VTE. METHODS AND ANALYSIS: This study is a single-arm, open-label, prospective interventional study. Forty patients aged from 20 to 75 years old at the time of consent who have been diagnosed with acute VTE and have active cancer are included. Patients are excluded if they have received thrombolytic therapy, have creatinine clearance of less than 30 mL/min, have expected a life expectancy of less than 6 months or have deep vein thrombosis limited to the distal lower leg. Eligible patients receive standard treatment with rivaroxaban (15 mg two times daily for 3 weeks, followed by 15 mg QD). The primary study endpoint is clot regression ratio as evaluated by contrast-enhanced CT imaging. CT imaging is obtained at baseline, 21±4 and 90±14 days after the start of rivaroxaban treatment. Secondary endpoints are the recurrence of VTE and haemorrhagic complications. ETHICS AND DISSEMINATION: This study was approved by the institutional review board of the Kyoto Prefectural University of Medicine. Study results will be disseminated through peer-reviewed journals.Trial registration numberUMIN000027793.

Chondroitinase injection improves keloid pathology by reorganizing the extracellular matrix with regenerated elastic fibers.

Keloids are a proliferative fibrotic disease characterized by abnormal accumulation of extracellular matrix in the dermis. Keloid lesions lack skin plasticity due to deficiencies in elastic fiber formation in the extracellular matrix. The loss of elastic fiber is caused by excessive accumulation of chondroitin sulfate (CS), a sulfated glycosaminoglycan. However, there is no radical cure for keloids. Using a model system, we show herein that treatment of keloid tissues with chondroitinase ABC, an enzyme that specifically digests CS, improves clinical features of keloids. Keloid tissues obtained from patients were grafted on nude mice, and chondroitinase ABC was injected into the grafted keloid tissues. Chondroitinase ABC treatment significantly reduced the volume of keloid implants concomitant with recovery of elastic fiber formation. These results suggest that chondroitinase ABC injection is an effective therapy for keloid.

Repeated enemas with hepatocyte growth factor selectively stimulate epithelial cell proliferation of injured mucosa in rats with experimental colitis.

AIMS: Hepatocyte growth factor (HGF) modulates intestinal epithelial cell proliferation and migration. We previously reported that systemic administration of recombinant human HGF (rh-HGF) ameliorated experimental colitis. However, an increase in serum HGF concentrations may induce undesired systemic effects, limiting the use of rh-HGF. To avoid possible side effects, we investigated the safety and efficacy of rectally administered rh-HGF as a treatment for experimental colitis. MAIN METHODS: We measured serum human HGF concentration following a single rectal enema of rh-HGF. Rats with 2,4,6-trinitrobenzene sulfonic acid (TNBS)- or dextran sulfate sodium (DSS)-induced colitis were treated with rectal enemas of rh-HGF once a day for seven days. The degree of mucosal injuries and the proliferative activity of the colon epithelium were examined. KEY FINDINGS: Rats administered a rectal enema of rh-HGF at a dose of 0.1 mg/ml or less had no detectable rh-HGF in the serum. Repeated enemas of rh-HGF at this dose significantly reduced mucosal injuries, both with respect to lesion size and inflammatory cell infiltration. This regimen also stimulated proliferation of epithelial cells surrounding injured mucosa; however, the cell proliferation of uninjured mucosa was not affected by this local treatment. SIGNIFICANCE: Rectally administered rh-HGF selectively accelerates the repair of injured mucosa in rat experimental colitis without systemic exposure to HGF. Rectal enemas of HGF are thus a potential novel and safe therapy for IBD.

A safety and survival analysis of neoadjuvant bevacizumab with standard chemoradiation in a phase I/II study compared with standard chemoradiation in locally advanced rectal cancer.

INTRODUCTION: Bevacizumab is increasingly being tested with neoadjuvant regimens in patients with localized cancer, but its effects on metastasis and survival remain unknown. This study examines the long-term outcome of clinical stage II/III rectal cancer patients treated in a prospective phase II study of bevacizumab with chemoradiation and surgery. As a benchmark, we used data from an analysis of 42 patients with locally advanced rectal cancer treated with a contemporary approach of preoperative fluoropyrimidine-based radiation therapy. MATERIALS AND METHODS: Outcome analyses were performed on 32 patients treated prospectively with neoadjuvant bevacizumab, 5-fluorouracil, radiation therapy, and surgery as well as 42 patients treated with standard fluoropyrimidine-based chemoradiation. RESULTS: Overall survival, disease-free survival, and local control showed favorable trends in patients treated with bevacizumab with chemoradiation followed by surgery. Acute and postoperative toxicity appeared acceptable. CONCLUSIONS: Neoadjuvant bevacizumab with standard chemoradiation and surgery shows promising long-term efficacy and safety profiles in locally advanced rectal cancer patients.

[Successful deployment of a stent graft in the popliteal artery for pseudoaneurysm after acupuncture: a case report].

A 71-year-old man was admitted to our hospital because of swelling and pain in his right calf developing after acupuncture for intermittent claudication. Computed tomography with contrast medium revealed a large hematoma with contrast medium leakage in his right calf. Emergent angiography demonstrated a pseudoaneurysm of the right popliteal artery with severe stenosis. Intravascular ultrasound showed lumen narrowing with a large amount of concentric plaque and disruption of the vessel wall communicating to a large cavity outside. A polytetrafluoroethylene-covered Jostent graft was deployed into the stenotic lesion across the opening into the pseudoaneurysm cavity. Subsequent angiography showed no leakage of contrast medium. This unique case of pseudoaneurysm caused by acupuncture in the popliteal artery was treated successfully by endovascular repair.

Signet-ring cell carcinoma of the colon 7mm in size with peritonitis carcinomatosa.

A 72-year-old woman was admitted with a complaint of a sensation of abdominal fullness. Cytologic examination of ascites revealed many poorly differentiated adenocarcinoma cells. Barium enema study and colonoscopy revealed IIa+IIc-type carcinoma of the descending colon. Endoscopic mucosal resection was performed to determine the histological type and the depth of invasion. The resected tumor was 7 x 6 mm in size, and an amorphous pit pattern was observed in the depressed area by stereomicroscopy. Poorly differentiated adenocarcinoma with signet-ring cells had diffusely infiltrated into the deeper part of the submucosal layer. Immunohistochemical findings showed this tumor to have mucin derived from gastric foveolar epithelium, suggesting that the signet-ring cell carcinoma of the colon showed gastric differentiation. Primary signet-ring cell carcinoma of the colon and rectum is a rare form of adenocarcinoma of the large intestine and shows more malignant biological behavior than ordinary colorectal carcinoma. Early diagnosis and curative operation are important.