The entity of thermal-crush-avulsion hand injury (hot-press roller burns) treated with fast acting debriding enzymes (nexobrid): literature review and report of first case.

Hand burns are present in >60% of all burn cases and in fire mass casualty incidents even up to 100%. Most trauma and especially burns may be detrimental to the complex and delicate structures of the hand by direct injury, indirect BICS (Burn Induced Compartment Syndrome and interstitial high pressure) or by delayed or faulty treatment. BICS represents a special threat as the increasing swelling and oedema of the small diameter hand and forearm will exert pressure on the capillary/venous system, eventually ending in irreversible damage to the skin, nerves, muscle and vascular bed. Immediate release of constricting skin by incisional escharotomy and sometimes fasciotomy may arrest this vicious cycle: escharotomy is simple for experienced hand or burn surgeons, but they are not always present at the primary treatment site. The diagnosis of BICS is not simple either, as the direct measurement of interstitial/compartment pressure is rarely done. Burns caused by hot rollers such as industrial linen ironing machines are especially traumatic as besides the "simple" thermal burn, the hot rollers exert immense crushing pressure to the hand caught between the rollers. Over the last few years, several publications have described the role of a newly approved Bromelain derived enzymatic debriding agent (NexoBrid) for burns in general and hand burns in particular, and its ability to resolve or prevent BICS. We present a rare severe thermal/crush hand injury case where we were able to successfully treat the patient with NexoBrid enzymatic debridement-escharotomy.

Une atteinte des mains est observée dans plus de 60% des brûlures, et dans quasiment tous les cas de catastrophes. La plupart des traumaitismes, en particulier les brûlures, peuvent être délétères pour les structures complexes et délicates de la main. Ceci peut être dû à la brûlure elle même, à un syndrome compartimental (SC), à un traitement tardif ou mal conduit. Le SC est particulièrement dangereux dans les espaces ténus de l'avant bras et de la main. L'augmentation de pression consécutive à l'oedème obère la microcirculation, entraînant au bout du compte des lésions cutanées, nerveuses, vasculaires et musculaires irréversibles. La libération immédiate des tissus ainsi comprimés par incision de décharge cutanée voire aponévrotomie peut interrompre le cercle vicieux. Il s'agit d'un geste simple pour des chirurgiens spécialisés, malheureusement pas toujours disponibles sur le site du traitement initial. Le diagnostic de SC n'est pas toujours aisé si la mesure directe des pressions tissulaires n'est pas réalisée. Les brûlures dues à des rouleaux chauffés comme ceux des presses à repasser industrielles car, outre le dégagement de chaleur, les rouleaux exercent une pression intense sur la main coincée entre eux. Depuis quelques années, plusieurs articles on décrit le rôle d'un nouvel agent de débridement enzymatique à base de bromélaïne (Nexobrid) pour le traitement des brûlures dont celles des mains ainsi que ses capacité à prévenir et traiter les SC. Nous présentons ici un cas de main de presse avec utilisation, couronnée de succès, de Nexobrid.

Weekly docetaxel versus CMF as adjuvant chemotherapy for older women with early breast cancer: final results of the randomized phase III ELDA trial.

BACKGROUND: Evidence on adjuvant chemotherapy in older women with breast cancer is poor. We tested whether weekly docetaxel is more effective than standard chemotherapy. PATIENTS AND METHODS: We carried out a multicenter, randomized phase III study. Women aged 65-79, operated for breast cancer, with average to high risk of recurrence, were allocated 1 : 1 to CMF (cyclophosphamide 600 mg/m², methotrexate 40 mg/m², fluorouracil 600 mg/m², days 1, 8) or docetaxel (35 mg/m(2) days 1, 8, 15) every 4 weeks, for four or six cycles according to hormone receptor status. Primary end point was disease-free survival (DFS). A geriatric assessment was carried out. Quality of life (QoL) was assessed with EORTC C-30 and BR-23 questionnaires. RESULTS: From July 2003 to April 2011, 302 patients were randomized and 299 (152 allocated CMF and 147 docetaxel) were eligible. After 70-month median follow-up, 109 DFS events were observed. Unadjusted hazard ratio (HR) of DFS for docetaxel versus CMF was 1.21 [95% confidence interval (CI) 0.83-1.76, P = 0.32]; DFS estimate at 5 years was 0.69 with CMF and 0.65 with docetaxel. HR of death was 1.34 (95% CI 0.80-2.22, P = 0.26). There was no interaction between treatment arms and geriatric scales measuring patients' ability or comorbidities. Hematological toxicity, mucositis and nausea were worse with CMF; allergy, fatigue, hair loss, onychopathy, dysgeusia, diarrhea, abdominal pain, neuropathy, cardiac and skin toxicity were worse with docetaxel. One death was attributed to CMF and two to docetaxel. Increasing age, impairment in instrumental daily living activities, number of comorbidities and docetaxel treatment were independently associated with severe nonhematological toxicity. QoL was worse with docetaxel for nausea-vomiting, appetite loss, diarrhea, body image, future perspective, treatment side-effects and hair loss items. CONCLUSIONS: Weekly docetaxel is not more effective than standard CMF as adjuvant treatment of older women with breast cancer and worsens QoL and toxicity. CLINICALTRIALSGOV: NCT00331097.

The therapy of kidney cancer with biomolecular drugs.

PURPOSE: Over the last few years, targeted agents have assumed a predominant role in treatment of metastatic renal cell carcinoma (mRCC). Our aim is to discuss recent developments on this rapidly evolving topic. EVIDENCE SYNTHESIS: Sunitinib represents front-line standard treatment for the good- and intermediate prognosis groups of patients with clear cell renal carcinoma. Bevacizumab/interferon and pazopanib have also been FDA-approved as first-line agents, while sorafenib has moved toward second-line and later therapy. Temsirolimus, an mTOR inhibitor, is recommended as front line therapy for patients in the poor-risk group and is the best front-line choice for patients with non-clear cell histology. Another mTOR inhibitor, everolimus, has shown clinical benefit post-tyrosine kinasis inhibitors failure in a phase III study and is considered the standard of care in this setting. Novel prognostic and efficacy markers might help to define most appropriate therapeutic strategy. Best sequence of use of these effective agents in mRCC patients remains up to the discretion of treating physician. CONCLUSIONS: In light of the considerable advances in understanding the biology of mRCC, several new drugs have been recently developed, with an increasing number of treatment options. Several markers are under evaluation for diagnostic, prognostic and efficacy purposes. A treatment algorithm, based on the best scientific evidence produce so far, is presented and it will evolve as data from ongoing trials will be available.

Treatment of advanced adenocarcinomas of the exocrine pancreas and the gallbladder with 5-fluorouracil, high dose levofolinic acid and oral hydroxyurea on a weekly schedule. Results of a multicenter study of the Southern Italy Oncology Group (G.O.I.M.).

BACKGROUND: To date there is no established chemotherapeutic treatment for patients with unresectable locally advanced and/or metastatic carcinomas of the exocrine pancreas or the gallbladder. A multicenter Phase II trial has been performed by the Southern Italy Oncology Group with the aim of evaluating the clinical effectiveness and tolerability of weekly 5-fluorouracil (5-FU) in modulation with intravenous (i.v.) high dose levofolinic acid and oral hydroxyurea. METHODS: A total of 70 patients fulfilling the standard eligibility for a Phase II study were enrolled in the trial. Forty patients had advanced pancreatic adenocarcinoma and 30 had advanced gallbladder carcinoma. The treatment schedule was: levofolinic acid, 100 mg/m2, in 500 mL of normal saline over 2-hour infusion followed by 5-FU, 600 mg/m2 i.v. bolus, and oral hydroxyurea, 1000 mg/m2, for 1 day every week for 6 consecutive weeks followed by 15 days of rest. RESULTS: Among the 40 patients with pancreatic adenocarcinoma, 5 (12.5%; 95% confidence level [CL], 8.5-16.5%) showed a partial response with a median duration of 5.6+ months, and 13 had stable disease. Twenty-two patients progressed. Median survival was 5.8 months. Among patients with advanced gallbladder carcinoma, 9 of 30 had a partial response (30%; 95% CL, 26-34%) with a median duration of 6.5 months, and 8 (27%) had stabilization of disease. Thirteen patients showed progressive disease. Median overall survival was 8 months. Toxicity was mild, with Grade 1 to 2 leukopenia and gastrointestinal toxicity the most frequent side effects. No chemotherapy-related deaths were observed. CONCLUSIONS: 5-FU in modulation with i.v. levofolinic acid and oral hydroxyurea on a weekly schedule is well tolerated by the vast majority of patients with locally advanced and/or metastatic carcinoma of the pancreas or the gallbladder. Although response rate and overall survival for patients with pancreatic adenocarcinoma are far from acceptable, the 30% overall response rate achieved in patients with advanced gallbladder carcinoma suggests that 5-FU in modulation with levofolinic acid and hydroxyurea is active in this neoplasm. The combination of modulated 5-FU with other antineoplastic drugs seems worthy of clinical testing in further controlled trials.

A simple method for the assay of Bordetella pertussis adenylate cyclase employing 31P nuclear magnetic resonance spectroscopy.

A simple method for the simultaneous assay of both substrate utilization and product formation by Bordetella pertussis adenylate cyclase has been developed. This method involves measurement of ATP remaining in the reaction mixture and cyclic 3',5'-AMP (cAMP) formation by 31p-NMR spectroscopy. No separation of the nucleotides is required. The measurement of the rate of cAMP formation compared very well with other methods that require separation of product from the substrate. With this method it has been possible to show calmodulin activation of B. pertussis adenylate cyclase and to demonstrate an inhibition of calmodulin activation by melittin. The inhibition of calmodulin-activated adenylate cyclase by melittin is not permanent and can be overcome by long-term incubation.