VITAL phase 2 study: Upfront 5-fluorouracil, mitomycin-C, panitumumab and radiotherapy treatment in nonmetastatic squamous cell carcinomas of the anal canal (GEMCAD 09-02).

AIM: VITAL, a phase II single-arm study, aimed to evaluate efficacy and safety of panitumumab addition to 5-fluorouracil (5-FU), mitomycin-C (MMC) and radiotherapy (RT) in patients with localized squamous cell carcinoma of the anal canal (SCCAC). METHODS: Adult, treatment-naïve SCCAC patients (Stage T2-T4, any N, M0) and ECOG-PS ≤2, received panitumumab (6 mg/kg, day 1 and Q2W; 8 weeks), 5-FU (1000 mg/m2 /d, days 1-4 and 29-32), MMC (10 mg/m2 , days 1 and 29) and RT 45 Gy (1.8 Gy/fraction) to the primary tumor and mesorectal, iliac and inguinal lymph nodes, plus 10-15 Gy boost dose to the primary tumor and affected lymph nodes. The primary objective was disease free survival rate (DFS) at 3-years (expected 3-year DFS rate: 73.7 ± 12%). RESULTS: Fifty-eight patients (31 women; median age: 59 years; ECOG-PS 0-1:98%; TNM II [29%] (T2 or T3/N0/M0)/IIIA (T1-T3/N1/M0 or T4/N0/M0) [21%]/IIIB (T4/N1/M0 or any T/N2 or N3/M0) [47%]/nonevaluable [4%]) were included. The median follow-up was 45 months. The 3-year DFS rate was 61.1% (95% CI: 47.1, 72.4). The 3-year overall survival rate was 78.4% (95% CI: 65.1, 87.1). Eighteen patients (31.0%) required a colostomy within 2 years posttreatment. Grade 3-4 toxicities were experienced by 53 (91%) patients. Most common grade 3-4 treatment-related events were radiation skin injury (40%) and neutropenia (24%). No toxic deaths occurred. Improved efficacy in colostomy-free survival and complete response rate was observed in human papilloma virus positive patients. CONCLUSIONS: Panitumumab addition to MMC-5FU regimen in SCCAC patients increases toxicity and does not improve patients' outcomes. RT plus MMC-5FU remains the standard of care for localized SCCAC patients.

Preliminary readings of antimicrobial susceptibility panels: A simple, fast and inexpensive way to detect bacterial resistance and enhance antibiotic treatment of bloodstream infections.

Increasing incidence of resistant bacteria needs faster identification (ID) and antibiotic susceptibility testing (AST) in order to improve antimicrobial treatment of severe infections. We propose a preliminary reading of the AST MicroScan® panels coupled with mass spectrometry ID. A total of 157 bacterial clinical isolates were processed for routine ID and AST (in 22 cases, ID and AST were performed directly from positive blood culture bottles). For gram-negatives, data from the initial and final readings were recorded and compared [89.9% category agreement (CA), 6.9% very major errors (VME)]. In adition all the 32 ESBL producers were detected at 5.3-8.6 hours. For Staphylococcus aureus, all the 16 MRSA isolates were detected at 4.5 to 7.5 hours. Thus, we find our preliminary readings approach as a simple, inexpensive and reliable way to detect and identify the most prevalent resistant bacteria in our institution on the same day that ID/AST is performed.

Biodistribution of different sized nanoparticles assessed by positron emission tomography: a general strategy for direct activation of metal oxide particles.

The extraordinary small size of NPs makes them difficult to detect and quantify once distributed in a material or biological system. We present a simple and straightforward method for the direct proton beam activation of synthetic or commercially available aluminum oxide NPs (Al2O3 NPs) via the 16O(p,α)13N nuclear reaction in order to assess their biological fate using positron emission tomography (PET). The radiolabeling of the NPs does not alter their surface or structural properties as demonstrated by TEM, DLS, and ζ-potential measurements. The incorporation of radioactive 13N atoms in the Al2O3 NPs allowed the study of the biodistribution of the metal oxide NPs in rats after intravenous administration via PET. Despite the short half-life of 13N (9.97 min), the accumulation of NPs in different organs could be measured during the first 68 min after administration. The percentage amount of radioactivity per organ was calculated to evaluate the relative amount of NPs per organ. This simple and robust activation strategy can be applied to any synthetic or commercially available metal oxide particle.

Factors associated with intolerance after refeeding in mild acute pancreatitis.

OBJECTIVES: This study aimed to describe the mode of refeeding, frequency of intolerance, and related factors in mild acute pancreatitis (AP). METHODS: We included all cases of mild AP between January 2007 and December 2009 in an observational, descriptive, and retrospective study. We analyzed demographic and etiological data, admission variables, treatment, refeeding mode, intolerance frequency, and treatment. Intolerance-related variables were determined using a Cox regression. RESULTS: Two-hundred thirty-two patients were included (median age, 74.3 years, bedside index for severity in AP score, 1). Oral diet was reintroduced at 3 days (range, 0-11 days) in 90.9% of cases with a liquid diet. Intolerance to refeeding appeared in 28 patients (12.1%) at a median time of 1 day (range, 0-14 days). Oral diet was reduced or suspended in 71.4%; analgesic and antiemetic drugs were required in 64% and 35.7% of patients, respectively. The variables independently associated with intolerance to refeeding were choledocholithiasis (hazard ratio [HR], 12.35; 95% confidence interval [CI], 2.98-51.19; P = 0.001), fasting time (HR, 1.33; 95% CI, 1.09-1.63; P = 0.005), refeeding with complete diet (HR, 4.93; 95% CI, 1.66-14.66; P = 0.04), length of symptoms before admission (HR, 1.004; 95% CI, 1.001-1.006; P = 0.012), and metamizole dose (HR, 1.11; 95% CI, 1.02-1.21; P = 0.014). CONCLUSIONS: Intolerance to refeeding is an infrequent event. We have identified several factors independently associated with intolerance.

Ligaria cuneifolia flavonoid fractions modulate cell growth of normal lymphocytes and tumor cells as well as multidrug resistant cells.

Flavonoids are ubiquitous compounds present in plant extracts. They represent a major active component of the plant extract and are often known for their anti-inflammatory and anti-tumor effects. Previously, we demonstrated that Ligaria cuneifolia (R et P) Tiegh. (Loranthaceae) extracts inhibit proliferation of murine mitogen-activated lymphocytes as well as murine T leukaemia (LB) and breast tumor cells (MMT). The aim of this study was to assess the anti-proliferative and pro-apoptotic activities of three separate flavonoid fractions derived from L. cuneifolia whole extract (aqueous, methanolic and ethyl acetate) on normal and tumor cells. This was performed as a bio-guided approach leading to the isolation and identification of the active compounds responsible for the effects observed with the whole extract. Results showed that the three fractions differed in the amount and type of compounds found. Only the ethyl acetate flavonoid fraction (100 microg/ml) was able to inhibit significantly the proliferation of Con A stimulated splenocytes or LB and MMT cells. Inhibition of proliferation was mediated by apoptosis as determined by morphology and DNA hypodiploidy. The ethyl acetate fraction modified mRNA expression of IL-2, IL-10 and TGF-beta, while the methanol fraction only modified IL-10 mRNA on LB cells. Our results show that the ethyl acetate flavonoid fraction contains the most active compound/s and is the potential candidate to isolate the active compound/s responsible for the effects observed with L. cuneifolia whole extract.

Phoradendron liga (Gill. ex H. et A.) Eichl. (Viscaceae) used in folk medicine: anatomical, phytochemical, and immunochemical studies.

Phoradendron liga (Gill. ex H. et A.) Eichl. is a Viscaceae widely distributed in Argentina. It has been commonly used in folk medicine as a substitute of the European mistletoe (Viscum album L.) to decrease high blood pressure due to their external similarity. In this study, the anatomical features as well as micromolecular and macromolecular analysis of this species are reported. Anatomical study has shown that Phoradendron liga presents as anatomic features: papillous cuticle, clusters in leaves and stems, and isodiametric stone cells only in stems. The analysis of flavonoids showed that this species produces C-glycosylflavones and 3-desoxyproanthocyanidins. Protein study showed a protein pattern with components ranging from 14 to 90 kDa and the presence of related epitopes between the species was demonstrated by cross recognition using anti-Phoradendron and anti-Viscum antisera of both species by Western blot assay. In addition, a galactose specific lectin (L-Phl) was isolated form Phoradendron liga extracts. These results are part of a comprehensive project on Argentine hemiparasite species destinated to be applied to quality control of commercial samples and disclosed their potential use as a potential source for immunomodulatory compounds.