Early intervention with adalimumab may contribute to favorable clinical efficacy in patients with Crohn's disease.

BACKGROUND: We evaluated the clinical efficacy of adalimumab (ADA) for Crohn's disease (CD) and analyzed predictive factors for clinical remission and long-term prognosis. METHODS: We retrospectively reviewed the medical records of 45 patients treated with ADA for CD at Keio University Hospital between October 2010 and March 2014. Clinical remission was defined as a Harvey-Bradshaw index of ≤4. RESULTS: Twenty-eight of 45 patients (62.2%) achieved clinical remission at week 4. Among these 28 patients, 18 patients (64.3%) maintained clinical remission at week 26, and among these, 16 patients (88.9%) maintained clinical remission at week 52. Absence of a history of bowel resection and absence of prior anti-tumor necrosis factor (anti-TNF) therapy were significant predictive factors for clinical remission at week 4 upon multivariate logistic regression analyses. Younger age and a disease duration of ≤3 years correlated with clinical remission at week 26 upon univariate analyses. Patients without a history of bowel resection showed significantly better long-term prognosis than those with a history of bowel resection (p = 0.01). None of the patients contracted a serious infectious disease. CONCLUSIONS: Younger age, shorter duration of disease, being naive to anti-TNF antagonists, and absence of a history of bowel resection were associated with the efficacy of ADA in CD patients.

A case of intestinal Behçet's disease treated with infliximab monotherapy who successfully maintained clinical remission and complete mucosal healing for six years.

Behçet's disease is a chronic relapsing disease with multiple organ system involvement, including the gastrointestinal tract, which is known as intestinal Behçet's disease. Intestinal Behçet's disease is often resistant to empirical treatments such as 5-aminosalicylic acid, immunomodulators and steroids and often causes a perforation, requiring surgical resection. Therefore, intestinal lesions are considered to be a poor prognostic factor in Behçet's disease. Recently, several reports have demonstrated the efficacy of anti-TNFα monoclonal antibodies, such as infliximab, against intestinal Behçet's disease, however, it remains unknown whether anti-TNFα therapy can improve the prognosis of patients with intestinal Behçet's disease. We herein report the case of an adult female patient with intestinal Behçet's disease who responded well to the induction therapy with infliximab, and has been maintained in remission by scheduled administration of infliximab. Her C-reactive protein level has been sustained at a negative level, and endoscopic findings revealed complete mucosal healing. Therefore, infliximab may have the potential to induce "sustained deep remission" in patients with intestinal Behçet's disease.

A novel fusicoccin derivative preferentially targets hypoxic tumor cells and inhibits tumor growth in xenografts.

Malignant cells in solid tumors survive under prolonged hypoxia and can be a source of resistance to current cancer therapies. Tumor hypoxia is also associated with a more malignant phenotype and poor survival in cancer patients. Recent progress in our understanding of the biology of tumor cells under hypoxia has led to increased attention on targeting hypoxia for cancer therapy. We report here that a novel fusicoccin derivative (ISIR-042), but not its parent or related compounds such as fusicoccin A and cotylenin A, is more cytotoxic to hypoxic cells than to normoxic cells. The hypoxia-induced accumulation of hypoxia-inducible factor (HIF)-1α and the phosphorylation of Akt were effectively inhibited by treatment with ISIR-042, suggesting that the preferential cytotoxicity toward hypoxic cells is associated with a reduction of HIF-1α and Akt activation. ISIR-042 inhibited the growth of human pancreatic cancer MIAPaCa-2 cells while sparing normal endothelial cells, and significantly inhibited the growth of MIAPaCa-2 cells as xenografts without apparent adverse effects. Pancreatic cancer cells expressing CD24 and CD44 exhibited characteristics of stem cells. Treatment with gemcitabine increased this stem cell-enriched population, and this effect was significantly inhibited by ISIR-042, suggesting that ISIR- 042 preferentially inhibits stem/progenitors in pancreatic cancer cell lines compared with chemotherapeutic agents. These results suggest that ISIR-042 may be a potential therapeutic agent for hypoxic tumors such as pancreatic cancer.

Recovery of sensitivity in the hand after reconstruction with arterialised venous flaps.

Loss of soft tissues of the fingers were repaired in 22 patients using 25 arterialised venous flaps harvested from the thenar, hypothenar, or forearm regions. Twenty-one of the flaps survived completely, 16 of which were raised from the thenar or hypothenar region, and the other five from the forearm region. We studied the sensory recovery and skin characteristics of the flaps harvested from the three regions. Good sensory recovery was obtained for the thenar or hypothenar venous flaps, which were characterised by durable skin and suitable texture for replacement of defects in the finger pulp. On the other hand, no moving two-point discrimination was recorded during the follow-up period in the group given forearm venous flaps. These flaps showed instability during pinching and grasping. However, larger flaps and longer veins can be harvested from the forearm region. This type of flap is therefore considered useful for covering dorsal defects of the finger or large and multiple skin defects.