Management of skin toxicity associated with cetuximab treatment in combination with chemotherapy or radiotherapy

Background.

Cetuximab was demonstrated by clinical trials to improve response rate and survival of patients with metastatic and nonresectable colorectal cancer or carcinoma of the head and neck. Appropriate management of skin toxicity associated with epidermal growth factor receptor inhibitor (EGFR-i) therapy is necessary to allow adequate drug administration and to improve quality of life and outcomes.

Methods.

A group of Italian Experts produced recommendations for skin toxicity management using the RAND/UCLA Appropriateness Method. Statements were generated on the basis of a systematic revision of the literature and voted twice by a panel of 40 expert physicians; the second vote was preceded by a meeting of the panelists.

Results.

Skin toxicity included skin rash, skin dryness, pruritus, paronychia, hair abnormality, and mucositis. Recommendations for prophylaxis and therapeutic interventions for each type of toxicity were proposed.

Conclusions.

Interventions that were considered appropriate to improve compliance and outcomes of cancer patients treated with EGFR-i were identified.     

Denosumab对绝以后骨质疏松妇女发生骨折的预防作用

背景及目的：Denosumab为一种人类单克隆抗体,它是核因子B配体(TANK)的受体激活剂(RANKL),RANKL,能够阻断该受体与RANK结合,从而抑制破骨细胞的生长及作用,减少骨的再吸收,增强骨密度.本研究分析了该药物对绝经后妇女骨质疏松症的预防作用.     

Incidence of neoplastic donors in Organizzazione Centro Sud Trapianti area during the 2003-2005 period

The aim of this study is to evaluate the incidence of malignant tumors in cadaver donors and the possibility of neoplastic disease transmission to the recipients in the Organizzazione Centro Sud Trapianti (OCST) area. Among 1744 potential donors identified from 2003 to 2005, 125 (7.1%) showed an elevated malignant neoplastic risk. In 2003 a malignant tumor was diagnosed in 60 donors of mean age 59.6 +/- 19.9 years (median 62.5, M:36 F:24); in 2004, 33 donors of mean age, 61.4 +/- 15.9 years (median 63, M:19 F:14); in 2005, 32 donors of mean age of 62.8 +/- 15.5 years (median 65.5, M:20 F:12). Prostatic cancer was the most common tumor (23.2%). In 101 of 125 cases (80.8%) the tumor was diagnosed before organ retrieval, in 23 (18.4%) cases, during the donor operation but before the transplant, and in one case (0.8%) after transplantation. Each tumor was evaluated according to the histologic types and grades. From 12 of those donors with neoplasia, 24 organs were retrieved (10 livers, 11 kidneys, 3 hearts) transplanted in 23 recipients (one liver-kidney combined transplant). Three recipients died during the perisurgical period due to causes unrelated to the tumor and therefore were not considered in the follow-up evaluation. Among the remaining nine recipients who had a mean follow-up of 38.83 months (range 9-42), no donor-transmitted disease has become apparent by imaging control. A careful donor evaluation including histologic grading and strict application of Centro Nazionale Trapianti guidelines allowed us to use donors with malignant tumors in selected cases with an apparently reduced risk of transmitted neoplastic disease.     

Role of sildenafil in acute posttransplant right ventricular dysfunction: successful experience in 13 consecutive patients

BACKGROUND: Superimposed acute right ventricular dysfunction in the setting of preexisting pulmonary hypertension is a nearly fatal complication after heart transplantation. The optimal treatment modality remains a matter of debate. Recently, sildenafil citrate, a nonselective pulmonary vasodilator, has gained popularity in the treatment of pulmonary hypertension in transplant candidates. METHODS: Herein we have presented a series of 13 patients in whom sildenafil was used to treat right ventricular dysfunction and pulmonary hypertension as detected by transesophageal echocardiography and Swan-Ganz right heart catheterization after heart transplant. Their characteristics were mean age 49+/-11.4 years; 38.4% with previous cardiac procedures, 30.8% status I, basal pulmonary vascular resistance index 10.4+/-4.6 WoodU, mean transpulmonary gradient 18.7+/-5.4 mmHg. In addition to conventional inodilator support, we administered 1 to 3 mg per kilogram of sildenafil. Complete hemodynamic measurements were obtained before and after the institution of the therapy and at 1-month follow-up. RESULTS: Within the first 72 hours, acute right ventricular dysfunction resolved in all cases without untoward side effects or significant systemic impact. Sildenafil significantly decreased the transpulmonary gradient and pulmonary vascular resistance index relative to baseline values; 5.6+/-1.82 versus 10.4+/-4.6 WU, (P< .05), 13.5+/-3.4 mm Hg versus 18.7+/-5.4 mm Hg (P< .05), respectively. Improved indices of right ventricular function were observed on echocardiographic monitoring. After 1 month, sildenafil treatment was discontinued. CONCLUSION: Management of acute right ventricular dysfunction in heart transplant recipients with pulmonary hypertension using sildenafil proved safe and effective.     

Increased expression of tissue plasminogen activator and its inhibitor and reduced fibrinolytic potential of human endothelial cells cultured in elevated glucose.

In diabetic patients, elevated plasma levels of t-PA and PAI-1 accompany impaired fibrinolysis. To identify mechanisms for these abnormalities, we examined whether vascular endothelial cells exposed to high glucose upregulate t-PA and PAI-1 production and whether ambient PA activity is decreased concomitantly. In 17 cultures of human umbilical vein endothelial cells grown to confluency in 30 mM glucose, the t-PA antigen released to the medium in 24 h was (median) 52 ng/10(6) cells (range 10-384) and the PAI-1 antigen was 872 ng/10(6) cells (range 217-2074)--both greater (P less than 0.02) than the amounts released by paired control cultures grown in 5 mM glucose--29 ng/10(6) cells (range 7.5-216) and 461 ng/10(6) cells (range 230-3215), respectively. In the presence of high glucose, the steady-state levels of t-PA and PAI-1 mRNAs were increased correspondingly (median 142 and 183% of control, respectively, P less than 0.05); high glucose per se and hypertonicity contributed to the upregulation in additive fashion. The PA activity of conditioned medium from cultures exposed to high glucose was 0.4 IU/ml (range 0.2-0.6), which was significantly lower (P less than 0.02) than the PA activity of control medium (0.5 IU/ml, range 0.2-0.9). No difference was observed when comparing the PA activities of acidified conditioned media, expected to be depleted of inhibitors. Thus, high glucose coordinately upregulates endothelial t-PA and PAI-1 expression through effects exerted at the pretranslational level and enhanced by even mild degrees of hypertonicity.(ABSTRACT TRUNCATED AT 250 WORDS)