Early diagnosis of anastomotic leakage after colorectal surgery by the Dutch leakage score, serum procalcitonin and serum C-reactive protein: study protocol of a prospective multicentre observational study by the Italian ColoRectal Anastomotic Leakage (iC.

BACKGROUND: Anastomotic leakage (AL) is a dreaded major complication after colorectal surgery. There is no uniform definition of anastomotic dehiscence and leak. Over the years many risk factors have been identified (distance of anastomosis from anal verge, gender, BMI, ASA score) but none of these allows an early diagnosis of AL. The DUtch LeaKage (DULK) score, C reactive protein (CRP) and procalcitonin (PCT) have been identified as early predictors for anastomotic leakage starting from postoperative day (POD) 2-3. The study was designed to prospectively evaluate AL rates after colorectal resections, in order to give a definite answer to the need for clear risk factors, and testing the diagnostic yeld of DULK score and of laboratory markers. Methods and analysis. A prospective enrollment for all patients undergoing elective colorectal surgery with anastomosis carried out from September 2017 to September 2018 in 19 Italian surgical centers. OUTCOME MEASURES: preoperative risk factors of anastomotic leakage; operative parameters; leukocyte count, serum CRP, serum PCT and DULK score assessment on POD 2 and 3. Primary endpoint is AL; secondary endpoints are minor and major complications according to Clavien-Dindo classification; morbidity and mortality rates; readmission and reoperation rates, length of postoperative hospital stay (Retrospectively registered at ClinicalTrials.gov Identifier: NCT03560180, on June 18, 2018). Ethics. The ethics committee of the "Comitato Etico Regionale delle Marche - C.E.R.M." reviewed and approved this study protocol on September 7, 2017 (protocol no. 2017-0244-AS). All the participating centers submitted the protocol and obtained authorization from the local Institutional Review Board.

HIV-1 Tat mimetic of VEGF correlates with increased microvessels density in AIDS-related diffuse large B-cell and Burkitt lymphomas.

Angiogenic switch marks the beginning of tumor's strategy to acquire independent blood supply. In some subtypes of non-Hodgkin's lymphomas, higher local vascular endothelial growth factor (VEGF) expression correlates with increased microvessel density. However, this local VEGF expression is higher only in tumors with elevated expression of the receptors of the growth factor, suggesting an autocrine growth-promoting feedback loop. Several studies have indicated that VEGF receptors are also targeted by Tat protein from the HIV-1-infected cells. Given the similarity of the basic region of Tat to the angiogenic factors (basic fibroblast growth factor, VEGF), Tat mimics these proteins and binds to their receptors. We evaluated the role of HIV-1 Tat in regulating the level of VEGF expression and microvessel density in the AIDS-related diffuse large B-cell (DLBCL) and Burkitt lymphomas (BL). By luciferase assay, we showed that VEGF promoter activity was downregulated in vitro in cells transfected with Tat. Reduced VEGF protein expression in primary HIV-1 positive BL and DLBCL, compared to the negative cases, supported the findings of promoter downregulation from the cell lines. Microvascular density assessed by CD34 expression was, however, higher in HIV-1 positive than in HIV-1 negative tumors. These results suggest that Tat has a wider angiogenic role, besides the regulation of VEGF expression. Thus, targeting Tat protein itself and stabilizing transient silencing of VEGF expression or use of monoclonal antibodies against their receptors in the AIDS-associated tumors will open a window for future explorable pathways in the management of angiogenic phenotypes in the AIDS-associated non-Hodgkin's lymphomas.

Alcohol-free red wine enhances plasma antioxidant capacity in humans.

Moderate wine consumption is reputed to exert a protective effect against coronary heart disease (CHD). The nature of the protective compounds is unclear and the mechanisms are incompletely understood. We studied whether the nonalcoholic component of wine increases plasma antioxidant capacity measured as total radical-trapping antioxidant parameter (TRAP), and whether such an effect is associated with the presence of phenolic compounds in plasma. The TRAP and plasma levels of phenolic compounds were measured in 10 healthy subjects after the ingestion of 113 mL of tap water (control) and alcohol-free red and white wine at 1-wk intervals. Both alcohol-free wines possessed an in vitro dose-dependent peroxyl-radical activity, but red wine, with a polyphenol concentration of 363 +/- 48.0 mg/L quercetin equivalent (QE), was 20 times more active (40.0 +/- 0.1 mmol/L) than white wine (1.9 +/- 0.1 mmol/L), which has a polyphenol concentration of 31 +/- 1 mg QE/L. The ingestion of alcohol-free red wine caused significant increases in plasma TRAP values and polyphenol concentrations 50 min after ingestion. Alcohol-free white wine and water had no effects on either of the plasma values. The parallel and prompt increase of antioxidant status and of circulating levels of polyphenols in fasting subjects after bolus ingestion of a moderate amount of alcohol-free red wine suggests that polyphenols are absorbed in the upper gastrointestinal tract and might be directly involved in the in vivo antioxidant defenses.

Plasma (carotenoids, retinol, alpha-tocopherol) and tissue (carotenoids) levels after supplementation with beta-carotene in subjects with precancerous and cancerous lesions of sigmoid colon.

OBJECTIVES: (1) To compare tissue and plasma carotenoids status of healthy subjects and subjects with pre-cancer and cancer lesions; (2) to evaluate the effect of beta-carotene supplementation on the concentrations of other carotenoids in tissue (luteine + zeaxanthin, cryptoxanthin, lycopene, alpha-carotene) and in plasma and also retinol and alpha-tocopherol levels. DESIGN: Eighteen subjects were divided into three groups on the basis of colonoscopy and histological analytical findings: four healthy subjects (control group A); seven subjects affected by adenomatous polyps (group B with pre-cancer lesions); seven subjects suffering from colonic cancer (group C). Blood and colonic biopsy samples were taken (of colon and rectal mucosa) before and after beta-carotene supplementation in all subjects. Groups A and B received a daily dose of beta-carotene (30 mg/die) for 43 d. Group C's supplementation was terminated at the time which was performed, usually within 15 d. The tissue and plasma concentration of carotenoids, retinol and alpha-tocopherol were determined by high-performance liquid chromatography. RESULTS: The tissue concentrations of each carotenoid were similar in all the intestinal sites examined as regards groups A and B, although there was a high degree of intra individual variability within each group. Only beta-carotene made significant increases (P < 0.001) after supplementation. The subjects with cancer show tissue levels for each carotenoid lower than those of healthy subjects or subjects with polypous. The plasma levels of alpha-tocopherol did not change after supplementation while significant increases were noted of retinol, alpha-carotene (P < 0.01) and of beta-carotene (P < 0.001). CONCLUSIONS: The patients with colonic cancer seemed to undergo a significant reduction in their antioxidant reserves with respect to the normal subjects and or polyps. We can confirm that oral B-carotene supplementation induces also an increase in plasma alpha-carotene in all groups.

Application of a new high-performance liquid chromatographic method for measuring selected polyphenols in human plasma.

We developed a method to measure plasma levels of selected polyphenols before and after ingestion of green tea. Blood samples were obtained from four healthy women before and 30 and 50 min after the ingestion of 300 ml of green tea infusion. A 1-ml volume of plasma was hydrolysed with 0.5 M HCl-methanol (1:1, v/v) for 30 min at room temperature, extracted with ethyl acetate and separated by reversed-phase chromatography. Polyphenols were identified on the basis of their retention times and by spectrum analysis. Green tea caffeine has the same retention times as caffeic acid. Consumption of green tea produces a notable increase in the plasma levels of caffeine plus caffeic acid and the appearance of measurable levels of epigallocatechingallate. In conclusion, the method was found to have the requisite features of specificity and sensitivity for monitoring plasma levels of selected tea polyphenols.

Adult malnutrition: simple assessment techniques for use in emergencies.

The recent recognition of the problem of adult malnutrition requires methods for specifying the severity of undernutrition. The measurement of mid upper arm circumference (MUAC) can now be used as a screening method for underweight (normally assessed from the BMI) or as an additional criterion with the BMI to identify the preferential loss of peripheral tissue stores of fat and protein. By analysing and extrapolating anthropometric data from nine detailed adult surveys from Asia, Africa and the Pacific a series of MUAC cut-off points have now been identified to allow the screening of individual adults under extreme conditions, e.g. during famine. Grade 4 malnutrition is now specified for those with a MUAC < 200 mm for men and < 190 mm for women since these MUAC values correspond to the loss of fat stores at BMI of < 13. Food supplementation is clearly needed in these individuals. Extreme wasting (grade 5 malnutrition) corresponds to MUAC values of < 170 and < 160 mm for men and women respectively. These adults have extremely low BMI, i.e. about 10, have lost most, if not all, of their protein stores and are at a high risk of imminent death. These individuals will need immediate special feeding regimens to ensure their survival. The sex-specific MUAC values corresponding to BMI of 16, 13 and 10 can now therefore be used for rapid screening and the choice of remedial action.

In vivo antioxidant effect of green and black tea in man.

OBJECTIVE: Evaluation of the vitro antioxidant activity of green and black tea, their in vivo effect on plasma antioxidant potential in man and the effect of milk addition. DESIGN: The antioxidant activity of the tea, with and without milk, was tested in vitro by measuring the length of the peroxyl radical induced lag-phase. The in vivo activity was tested on two groups of five healthy adults. Each group ingested 300 ml of either black or green tea, after overnight fast. The experiment was repeated on a separate day, adding 100 ml whole milk to the tea (ratio 1:4 ). Five subjects acted as controls. The human plasma antioxidant capacity (TRAP) was measured before and 30, 50 and 80 min from the ingestion of tea. RESULTS: Both teas inhibited the in vitro peroxidation in a dose-dependent manner. Green tea was sixfold more potent than black tea. The addition of milk to either tea did not appreciably modify their in vitro antioxidant potential. In vivo, the ingestion of tea produced a significant increase of TRAP (P <0.05), similar in both teas, which peaked at 30-50 min. When tea was consumed with milk, their in vivo activity was totally inhibited. CONCLUSIONS: The paper shows that tea possesses a strong antioxidant activity in vitro which is believed to be exerted by its polyphenols moiety. It also provides compelling evidence that tea has also a potent in vivo activity in man. The promptness of the in vivo response suggests that the absorption of the bioactive components of tea takes place in the upper part of the gastrointestinal system. The inhibition of this effect by milk is thought to be due to the complexation of tea polyphenols by milk proteins. These findings might help to clarify the putative role of dietary poly- phenols in modulating oxidative stress in vivo.

Mediterranean diet, Italian-style: prototype of a healthy diet.

Since Keys' first observations in the 1960s, the Mediterranean diet has been under scrutiny by researchers and public health specialists for its health-promoting qualities. Detailed analyses of food surveys carried out in Italy at that time permitted a definition of an Italian-style Mediterranean diet, characterized by low total fat (< 30% of energy), low saturated fat (< 10% of energy), high complex carbohydrates, and high dietary fiber. The importance of the plant components of this dietary pattern became increasingly recognized as a result of advances in the understanding of the pathophysiology of chronic and degenerative diseases. Thus, the Mediterranean diet was found not only to produce favorable effects on blood lipid profiles, but also to protect against oxidative stress and carcinogenesis. However, possible unwanted effects, such as those on micronutrient bioavailability, also must be taken into account. In recent years, despite an increase in consumption of animal foods, the dietary profile of southern Italy has maintained its basic features, and vital statistics still demonstrate a comparative advantage of eating behaviors in Mediterranean countries.

Mediterranean diet pyramid: a cultural model for healthy eating.

We present a food pyramid that reflects Mediterranean dietary traditions, which historically have been associated with good health. This Mediterranean diet pyramid is based on food patterns typical of Crete, much of the rest of Greece, and southern Italy in the early 1960s, where adult life expectancy was among the highest in the world and rates of coronary heart disease, certain cancers, and other diet-related chronic diseases were among the lowest. Work in the field or kitchen resulted in a lifestyle that included regular physical activity and was associated with low rates of obesity. The diet is characterized by abundant plant foods (fruit, vegetables, breads, other forms of cereals, potatoes, beans, nuts, and seeds), fresh fruit as the typical daily dessert, olive oil as the principal source of fat, dairy products (principally cheese and yogurt), and fish and poultry consumed in low to moderate amounts, zero to four eggs consumed weekly, red meat consumed in low amounts, and wine consumed in low to moderate amounts, normally with meals. This diet is low in saturated fat (< or = 7-8% of energy), with total fat ranging from < 25% to > 35% of energy throughout the region. The pyramid describes a dietary pattern that is attractive for its famous palatability as well as for its health benefits.

Accumulation of beta-carotene in normal colorectal mucosa and colonic neoplastic lesions in humans.

The quantity of beta-carotene (BC) accumulated in colonic polyps and colonic cancerous tissue in humans in situ was determined relative to the quantity accumulated in normal colon and rectal tissue. Serum concentration of BC, retinol, and alpha-tocopherol and tissue BC concentration were determined by high-performance liquid chromatography in samples obtained before and after oral supplementation with BC (30 mg/day). The serum BC and retinol concentrations significantly increased in response to supplementation in control, polyp, and cancer patients, but there was no change in serum alpha-tocopherol concentration. The BC concentration in tissue (colon, rectum, and tumor) of cancer patients was significantly less than that in tissue samples from control and polyp patients. Relative to baseline values, BC accumulated to a significant extent in tissues from all patients, including polyp and tumor tissue, during supplementation. The results indicate that BC does accumulate in colonic neoplastic tissue in humans and may potentially be utilized to augment cytotoxicity of chemotherapeutics or to prevent malignant transformation of cells.

Partial calcanectomy for the treatment of osteomyelitis of the os calcis.

Chronic heel ulcerations in the insensate or bedridden patient have always been a difficult and frustrating condition to cure. When complicated by osteomyelitis, the patient must often resort to below-the-knee amputation. Presented here is a case report of the use of partial calcanectomy and primary closure for the treatment of osteomyelitis of the os calcis with ulceration. A discussion of indications, technique, and results is given.

Nonclostridial gas gangrene.

Although nonclostridial gas gangrene is not an unusual occurrence, relatively few cases including the distal lower extremity have been reported. Due to the serious nature of some of these infections, it is important for physicians to familiarize themselves with these nonclostridial crepitant infections, which are often confused with clostridial myonecrosis. Etiology, evaluation, and treatment is described by the authors. Also, a case study is presented.

Determinants of nutritional status in hospital patients in Italy.

The prevalence of protein-calorie malnutrition (PCM) and micronutrient deficiency (MND) at the time of admission and discharge from hospital was evaluated in 91 patients consecutively admitted to the Surgery Clinic of the University Hospital of Rome. Anthropometric parameters and circulating levels of vitamins (A, E, C, B1, and B2) and visceral proteins [retinol-binding protein (RBP, prealbumin (PA), and transferrin] were measured. Twenty-one patients (23%) had moderate to severe PCM, and 70 patients (77%) had normal nutritional status (NNS) at admission. Two patients with PCM died in the hospital. At discharge, the prevalence of PCM was unchanged in the remaining 19 patients. Single or multiple MND was observed initially in 71% of patients with PCM and in 36% with apparently normal nutritional status. Despite vitamin supplementation, MND was present at the time of discharge in 73% of patients with PCM and 44% with NNS. Nutritional status at the time of admission was assessed in hospitals in six different Italian cities. The criterion for admission to the study was the diagnosis of chronic (greater than 1 yr duration) illness (excluding cancer and multiple organ disorders). Two hundred eighty-four patients (145 males, 139 females), ages 25-88 yr, were selected. The findings indicated a high prevalence of MND (64%). Also, in disorders that usually do not have significant alterations of digestion or absorption, such as uncomplicated cardiorespiratory disease, the prevalence of MND was high (9-38%). The prevalence of MND was not related to body mass index (BMI). PCM was more common among patients with chronic gastrointestinal disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Fecalase: a model for activation of dietary glycosides to mutagens by intestinal flora.

Many substances in the plant kingdom and in man's diet occur as glycosides. Recent studies have indicated that many glycosides that are not mutagenic in tests such as the Salmonella test become mutagenic upon hydrolysis of the glycosidic linkages. The Salmonella test utilizes a liver homogenate to approximate mammalian metabolism but does not provide a source of the enzymes present in intestinal bacterial flora that hydrolyze the wide variety of glycosides present in nature. We describe a stable cell-free extract of human feces, fecalase, which is shown to contain various glycosidases that allow the in vitro activation of many natural glycosides to mutagens in the Salmonella/liver homogenate test. Many beverages, such as red wine (but apparently not white wine) and tea, contain glycosides of the mutagne quercetin. Red wine, red grape juice, and tea were mutagenic in the test when fecalase was added, and red wine contained considerable direct mutagenic activity in the absence of fecalase. The implications of quercetin mutagenicity and carcinogenicity are discussed.