Infections and Colon Surgery: Preliminary Results from a Surveillance Program in an Italian Hospital.

Surgical site infections (SSIs) represent a valid indicator of the healthcare quality. This study described the preliminary results of one-year active surveillance program on colon surgeries in a hospital in Molise region, central Italy. Patients who had undergone colon surgery according to National Healthcare Safety Network were included. Data on intervention, perioperative antibiotic prophylaxis, and SSIs occurrence were collected. Chi-square and Fisher's Exact test were used to evaluate any association between risk factors and SSIs. Sixty-eight patients (mean age 70.6 years) were included, and 44 (64.7%) were males. The most frequent interventions were right (n = 17, 25.0%) and left (n = 15, 22.0%) hemicolectomy. Surgical interventions were largely elective (n = 43, 63.2%) and with laparotomy (n = 56, 82.4%). During hospital stay, 10 (14.7%) SSIs were detected, including five superficial, three deep and two organ/space infections. Three (4.4%) additional SSIs were detected at post-discharge follow-up, for 13 (19.1%; CI95%: 9.7%-28.5%) total cases detected. Metronidazole plus Ceftriaxone (third generation cephalosporin) was the antibiotics combination mostly used (n = 36, 52.9%) for the perioperative antibiotic prophylaxis within 60 minutes of incision. The study underlines the need of improvements of the practices currently adopted, since SSIs could be significantly reduced through a multimodal strategy generating bundles. As third generation cephalosporins may facilitate resistant strains emergence, for perioperative prophylaxis in clean-contaminated interventions with entry into gastrointestinal tract, Cefazolin plus Metronidazole or only second generation cephalosporin are recommended. Due to the large variability of post-intervention antibiotic therapy, antimicrobial stewardship approach is strictly necessary.

Structural and biochemical studies of actin in complex with synthetic macrolide tail analogues.

The actin filament-binding and filament-severing activities of the aplyronine, kabiramide, and reidispongiolide families of marine macrolides are located within the hydrophobic tail region of the molecule. Two synthetic tail analogues of aplyronine C (SF-01 and GC-04) are shown to bind to G-actin with dissociation constants of (285±33) and (132±13) nM, respectively. The crystal structures of actin complexes with GC-04, SF-01, and kabiramide C reveal a conserved mode of tail binding within the cleft that forms between subdomains (SD) 1 and 3. Our studies support the view that filament severing is brought about by specific binding of the tail region to the SD1/SD3 cleft on the upper protomer, which displaces loop-D from the lower protomer on the same half-filament. With previous studies showing that the GC-04 analogue can sever actin filaments, it is argued that the shorter complex lifetime of tail analogues with F-actin would make them more effective at severing filaments compared with plasma gelsolin. Structure-based analyses are used to suggest more reactive or targetable forms of GC-04 and SF-01, which may serve to boost the capacity of the serum actin scavenging system, to generate antibody conjugates against tumor cell antigens, and to decrease sputum viscosity in children with cystic fibrosis.

Concomitant boost radiotherapy and multidrug chemotherapy in the neoadjuvant treatment of locally advanced rectal cancer: results of a phase II study.

BACKGROUND: An intensified multidrug chemotherapy regimen (raltitrexed plus oxaliplatin, Tom-Ox) plus concomitant boost radiotherapy, in the neoadjuvant treatment of locally advanced rectal cancer patients, was shown feasible in our previous study. The aim of this study was to evaluate the efficacy in terms of pathologic complete response to pre-operative therapy. MATERIAL AND METHODS: A Phase II study was designed and clinical stage T3-T4 and/ or N ≥ 1 patients were treated with concomitant boost radiotherapy (55 Gy/5 weeks) plus concurrent chemotherapy (Tom-Ox). The primary endpoint was the assessment of efficacy in terms of clinical and pathologic response to pre-operative therapy. According to the Gehan's design study, 25 patients were enrolled. Toxicity was assessed according to the RTOG-EORTC and CTCAE v.3.0 criteria. RESULTS: Twenty-five consecutive patients were treated. Twenty-two of the 25 (88%) patients had a partial clinical response at the time of pre-operative magnetic resonance imaging (MRI). Only one patient showed progressive systemic disease at pre-surgical revaluation and was subjected only to biopsy to evaluate pathological response. Twenty-four patients (96%) underwent surgery. Overall, pathologic complete response was observed in eight patients (32%; CI 0.95:12-55%) and only microscopic tumor foci (pTmic) in two patients (pT0-mic: 40%; CI 0.95:18-63%). Nineteen patients (76%) showed tumor down-staging. Proctitis and/or diarrhea were the most frequent acute side effects experienced. Eighteen patients had grade 1-2 toxicity (77%); whereas two patients experienced grade 3 toxicity (8%). Two-year Local control and actuarial Disease Free Survival were 100% and 91%, respectively. CONCLUSION. An intensified regimen of concomitant boost radiotherapy plus concurrent raltitrexed and oxaliplatin, can be safely administered in patients with locally advanced rectal cancer. This regimen produces high rates of pathological complete response. Based on available data, this type of treatment could be offered to patients with more advanced tumors (T4 or local recurrence).

Synthetic mimetics of actin-binding macrolides: rational design of actin-targeted drugs.

Actin polymerization and dynamics are involved in a wide range of cellular processes such as cell division and migration of tumor cells. At sites of cell lysis, such as those occurring during a stroke or inflammatory lung diseases, actin is released into the serum where it polymerizes, leading to problems with clot dissolution and sputum viscosity. Therefore, drugs that target these actin-mediated processes may provide one mechanism to treat these conditions. Marine-organism-derived macrolides, such as reidispongiolide A, can bind to, sever, and inhibit polymerization of actin. Our studies show that the function of these complex macrolides resides in their tail region, whereas the head group stabilizes the actin-drug complex. Synthetic compounds derived from this tail region could therefore be used as a mimetic of the natural product, providing a range of designer compounds to treat actin-associated diseases or as probes to study actin polymerization.