Enhanced recovery pathways in colorectal surgery: a consensus paper by the Associazione Chirurghi Ospedalieri Italiani (ACOI) and the PeriOperative Italian Society (POIS).

Enhanced Recovery After Surgery (ERAS) pathway is a multi-disciplinary, patient-centered protocol relying on the implementation of the best evidence-based perioperative practice. In the field of colorectal surgery, the application of ERAS programs is associated with up to 50% reduction of morbidity rates and up to 2.5 days reduction of postoperative hospital stay. However, widespread adoption of ERAS pathways is still yet to come, mainly because of the lack of proper information and communication. Purpose of this paper is to support the diffusion of ERAS pathways through a critical review of the existing evidence by members of the two national societies dealing with ERAS pathways in Italy, the PeriOperative Italian Society (POIS) and the Associazione Italiana Chirurghi Ospedalieri (ACOI), showing the results of a consensus development conference held at Matera, Italy, during the national ACOI Congress on June 10, 2019.

Effect of pomegranate peel extract on shelf life of strawberries: computational chemistry approaches to assess antifungal mechanisms involved.

In Italy Botrytis cinerea represents the most significant disease in strawberry crops and causes major quality and quantity losses in postharvest storage. An alternative strategy to the synthetic fungicides in crop defence could be the use of bioactive compounds with high antifungal activity. This research regards the use of Punica granatum peel extract to extend the shelf life of strawberry and the proposal of a possible mechanism for its antifungal activity. In vitro and in vivo tests showed the ability of pomegranate peel extract to control strawberry gray mould. Fourier transform near infrared spectroscopy showed a high correlation between spectra and disease severity then, a putative molecular mechanism for the interaction of punicalagin on ergosterol of fungal membrane was described by means of computational chemistry approaches. Molecular dynamics simulations were performed by using Gromacs to gain multiconformational representations of either punicalagin and an antifungal compound of clinical relevance, i.e. amphotericin B. The use of grid-based procedures, allowed to shed some light on the molecular mechanism featuring the antifungal activity of punicalagin.

Metachronous elastofibromas.

Elastofibroma Dorsi (EFD) is a rare pseudo-tumor characterized by the overgrowth of elastic fibers mixed to adipose and connective tissues typically growing in the subscapular region. This can be bilateral but only rarely synchronous affecting different anatomical sites at the same time. Hereby we present a case of a 42-year-old male patient found with three different metachronous elastofibromas: bilateral EFD and a further third localization by the right elbow. The two EFs in the subscapular region were resected. After surgery pain reoccurred on the right side. This required the implantation of a spinal electro-stimulator. The elbow lesion was not excised as it was asymptomatic.

Angiomegaly and arterial aneurysms.

Angiomegaly is characterized by an alteration in the elastic component of arterial and venous vessels determining their elongation and tortuousness. This involves an increased risk of thromboembolism and aneurysmal degeneration in affected subjects, even if they have been asymptomatic for a long time. The aim of this study is to demonstrate the correlation between angiomegaly and aneurysmal disease. A total of 163 patients suffering from a peripheral arterial aneurysm were included, 74 of these with an iliac aneurysm, 41 with a femoral aneurysm and 48 suffering from popliteal aneurysm. All patients were examined by color Doppler ultrasonography (CDU) and angio-CT with contrast medium. Eighteen cases of arteriomegaly were diagnosed, and the prevalence in the examined population was 11%. This study demonstrates the close association existing between aneurysms in peripheral arteries and arteriomegaly. Peripheral arterial aneurysms in association with arteriomegaly involve an increased risk of complications like thrombosis, embolism and rupture. The showed familiarity in the arteriomegaly incidence leads to predisposition of screening programs, using CDU, among relatives of patients affected by arteriomegaly and/or peripheral arterial aneurysms.

[Micromedullary thyroid carcinoma: school experience]. / Il microcarcinoma midollare della tiroide: esperienza di Scuola.

Medullary microcarcinomas occurrence are rare and fortuitous, it's usually related to the calcitonin measurement, that's the gold standard for the diagnosis. In other cases performing a thyroidectomy for a benign thyroid disease it's found a sub-centimeter tumor. Actually it's not clear the most appropriate surgical treatment for those kind of tumors because the number of cases in literature is limited and because there are different surgical approaches. In this study 17 patients were operated for medullary thyroid microcarcinoma and the Authors found central lymph node metastases in 33.3% of cases. The Authors, analyzing those results, think that total thyroidectomy with lymphadenectomy of the central compartement is the best choice in a sporadic microcarcinoma, while a total thyroidectomy without lymphadenectomy should be performed when the microcarcinomas are incidentals.

[Case-mix index and length of hospitalization]. / L'indice di case-mix e la durata della degenza.

The ACG (Adjusted Clinical Groups) case-mix system is a classification method of diseases of patients, focused on the person. Depending on the pattern of these morbid conditions, the ACG system assigns each patient to a single group (an ACG group), which allows to capture the effects of a group of diseases in estimates of resource use. Diseases are classified into a diagnostic group (ADG) according to 5 clinical dimensions: duration (acute, recurrent or chronic), severity (minor/major vs stable/unstable), diagnostic assessment (symptoms vs diseases), etiology (infectious, traumatic or other), specialty (medical, surgical, obstetric, ...). All diseases can be classified into these dimensions and into one of 32 groups. The ACG case-mix system uses an algorithm to classify each patient into one of 93 ACG categories. Each person is assigned to an ACG according to his ADG combination, his age and his gender. With the repayment system "case-mix", surgery has become central for all great hospitals in virtue of its great productive potential. The case-mix index is one of the factors which influence the duration of hospitalization. The case-mix system has emphasized the importance of the duration of hospitalization, encouraging the planning of programs in order to discharge patients early after surgical operations. It has also stimulated the surgical activity in operating units with "budget" forecasts in which resources are provided according to an expected level of specialist surgery.

Nitrogen management is essential to prevent tropical oil palm plantations from causing ground-level ozone pollution.

More than half the world's rainforest has been lost to agriculture since the Industrial Revolution. Among the most widespread tropical crops is oil palm (Elaeis guineensis): global production now exceeds 35 million tonnes per year. In Malaysia, for example, 13% of land area is now oil palm plantation, compared with 1% in 1974. There are enormous pressures to increase palm oil production for food, domestic products, and, especially, biofuels. Greater use of palm oil for biofuel production is predicated on the assumption that palm oil is an "environmentally friendly" fuel feedstock. Here we show, using measurements and models, that oil palm plantations in Malaysia directly emit more oxides of nitrogen and volatile organic compounds than rainforest. These compounds lead to the production of ground-level ozone (O(3)), an air pollutant that damages human health, plants, and materials, reduces crop productivity, and has effects on the Earth's climate. Our measurements show that, at present, O(3) concentrations do not differ significantly over rainforest and adjacent oil palm plantation landscapes. However, our model calculations predict that if concentrations of oxides of nitrogen in Borneo are allowed to reach those currently seen over rural North America and Europe, ground-level O(3) concentrations will reach 100 parts per billion (10(9)) volume (ppbv) and exceed levels known to be harmful to human health. Our study provides an early warning of the urgent need to develop policies that manage nitrogen emissions if the detrimental effects of palm oil production on air quality and climate are to be avoided.

Thyroid tissue remnants after "total thyroidectomy".

Total Thyroidectomy (TT) is a gold standard for benign bilateral pathologies and malignant pathologies of the thyroid. TT has numerous advantages over less radical approaches, such as the resolution of the thyroid pathology, avoidance of recurrences, and improved response to life-long substitutive organotherapy. TT has a negligible rate of recurrence. Near Total Thyroidectomy (NTT) is associated with a low rate of recurrence. Subtotal Thyroidectomy (ST), in which a portion of the thyroid gland is deliberately left in the thyroid lodge, has a considerably higher rate of recurrence. The incidence of complications with TT is similar to that with other techniques of thyroid exeresis. However, despite the radical intent of surgeons, a real TT is not always carried out. The complete removal of all the thyroid tissue employing TT is not the norm and micro/macroscopic remnants almost always remain. The literature on these tissue remnants is often based on techniques that are not very accurate in terms of determining the diameters of the tissue remaining. In our study, conducted by colour echo-doppler of the thyroid lodge in 102 patients who had undergone TT for benign thyroid pathologies, we demonstrated significant thyroid tissue remnants after TT in 34 cases of 102 (33,3%). Therefore, out of a total of 102 so-called "total thyroidectomies", only 68 (66,7%) were really total, whereas 12 patients (11,76%) had near total thyroidectomy, leaving tissue remnants < 1 cm, and 22 patients (21,57%) had subtotal thyroidectomy, with tissue remnants > or = 1 cm.

[Medullary thyroid carcinoma: a study about 28 operated patients]. / Carcinoma midollare della tiroide: studio su 28 casi operati.

In this study on 28 operated patients, the Authors show that total thyroidectomy with elective central neck dissection and ipsilateral neck dissection is the most appropriate surgical treatment for medullary thyroid carcinoma. Pathologic study on lymph nodes removed in central and in latero-cervical compartments showed malignancy respectively in 75% and in 70% of the cases. However the role of elective ipsilateral lateral neck dissection remains controversial.

[Retroperitoneal giant mixed sarcoma. Case report]. / Un caso di sarcoma misto retroperitoneale gigante.

The Authors present a rare case of voluminous retroperitoneal tumor in a 41 years old woman. CT scan showed a solid abdominal expansive mass, with compression and displacement of the left lobe of the liver, spleen, stomach, pancreas, and left kidney. The patient underwent surgery for excision of a giant retroperitoneal mass. Surgery was uneventful. The patients recovered well. Histology showed a mixed liposarcoma and angiosarcoma with high grade of malignancy and positivity for vimentin, factor VIII, CD34, CD31 and negativity for S-100, CD68, AMS, AML. The prognosis of these tumours is closely related to local recurrence, histological type, size and radical surgery. A low-grade malignancy tumor, small sized and completely resected leads to a good prognosis. Radiation therapy and chemotherapy do not seem to have a strong influence on the prognosis. An aggressive surgical approach is the first choice for the treatment of such tumors. The resection of adjacent organs may be required for radical surgery.

Challenges in quantifying biosphere-atmosphere exchange of nitrogen species.

Recent research in nitrogen exchange with the atmosphere has separated research communities according to N form. The integrated perspective needed to quantify the net effect of N on greenhouse-gas balance is being addressed by the NitroEurope Integrated Project (NEU). Recent advances have depended on improved methodologies, while ongoing challenges include gas-aerosol interactions, organic nitrogen and N(2) fluxes. The NEU strategy applies a 3-tier Flux Network together with a Manipulation Network of global-change experiments, linked by common protocols to facilitate model application. Substantial progress has been made in modelling N fluxes, especially for N(2)O, NO and bi-directional NH(3) exchange. Landscape analysis represents an emerging challenge to address the spatial interactions between farms, fields, ecosystems, catchments and air dispersion/deposition. European up-scaling of N fluxes is highly uncertain and a key priority is for better data on agricultural practices. Finally, attention is needed to develop N flux verification procedures to assess compliance with international protocols.

Ipriflavone prevents radial bone loss in postmenopausal women with low bone mass over 2 years.

Two hundred and fifty-five postmenopausal women with distal forearm bone mineral density (BMD) 1 SD below the mean value for normal age-matched postmenopausal subjects were randomly allocated to a 2-year treatment with oral ipriflavone (200 mg t.i.d) or a matched placebo, according to a double-masked, parallel group design. All patients also received a 1 g/day calcium supplement. Distal radius BMD and bone metabolism markers were measured at baseline, and every 6 months. Blood haematology and chemistry and physical parameters were monitored at the same time. One hundred and ninety-six patients completed 2 years of treatment. BMD changes from baseline were analysed according to valid completers (VC) and intention to treat (ITT) analyses. In both cases radial BMD was maintained in patients treated with ipriflavone while in decrease in those receiving the placebo, the between-treatment difference being significant at year 1 and year 2. Urinary hydroxyproline/creatinine levels were decreased in the ipriflavone-treated group and increased in the placebo group, with a significant between-treatment difference. Adverse reactions, mainly gastrointestinal, occurred to a similar extent in the two treatment groups.

Effect of chronic treatment with ipriflavone in postmenopausal women with low bone mass.

We present the results of two multicenter, double-blind, placebo-controlled, 2-year studies to evaluate the efficacy and tolerability of ipriflavone in postmenopausal women (PMW) with low bone mass. 453 PMW (aged 50-65 years) with a vertebral (VMD) or radial (RMD) mineral density value 1 SD lower compared with age-matched controls, were randomly selected to receive oral ipriflavone (200 mg T.I.D. at meals) or matching placebo, plus 1 g oral calcium daily. Vertebral (study A, by dual X-ray absorptiometry-DXA) and radial (study B, by dual photon absorptiometry-DPA) bone density, serum bone Gla-protein (BGP), and urinary hydroxyproline/creatinine (HOP/Cr) were measured every 6 months. In both studies, the Valid Completers (VC) analysis showed a maintenance of bone mass in ipriflavone-treated women, whereas in the placebo group, bone mineral density (BMD) was significantly decreased. The final outcome was a bone-sparing effect of 1.6% in study A, and of 3.5% in study B after 2 years. The Intention to Treat (ITT) analysis confirmed the decrease in the placebo group, with no changes in ipriflavone-treated women. A significant (P < 0.05) between-treatment difference was found in both studies. Biochemical markers of bone turnover decreased in patients treated with ipriflavone, thus suggesting a reduction of bone turnover rate. Twenty-six women treated with ipriflavone and 28 receiving the placebo dropped out because of side effects, mainly gastrointestinal. The compliance to the oral long-term treatment was good. The results of these studies show that ipriflavone is able to prevent both axial and peripheral bone loss in PMW with low bone mass, and is well tolerated.

Adducts to nuclear DNA and mitochondrial DNA as biomarkers in chemoprevention.

DNA adducts are biomarkers evaluating the biologically effective dose of carcinogens, which reflects, more realistically than the external exposure dose, an enhanced risk of developing cancer. Likewise, inhibition of DNA adduct formation can be assumed as an indicator of decreased risk. Molecular dosimetry techniques can be exploited in anticarcinogenicity studies in animal models as well as in Phase II clinical chemoprevention trials. We have extensively used these end points in animal studies using individual carcinogens and complex mixtures. As assessed by 32P-postlabelling, DNA adducts were formed in the liver of rats fed a diet supplemented with 2-acetylaminofluorene. DNA adducts were detected by synchronous fluorescence spectrophotometry (SFS) in rat liver, lung, heart and testis following intratracheal (l.t) instillations of benzo[a]pyrene. The whole-body exposure of rats to mainstream cigarette smoke resulted in the appearance of DNA adducts in lung, heart, aorta and kidney, whereas adducts were not detected by SFS in liver, brain, oesophagus and testis. Moreover, typical diagonal radioactive zones and multiple DNA adducts were revealed by 32P-postlabelling in the tracheal epithelium, nasal mucosa, aorta and testis of smoke-exposed rats. Formation of adducts to lung DNA, as assessed by both 32P-postlabelling and SFS, also occurred in rats receiving i.t. instillations of air particulate extracts from polluted urban and rural areas. The oral administration of the thiol N-acetylcysteine (NAC) significantly inhibited the formation of DNA adducts in all organs of the rats exposed to the aforementioned carcinogens, which correlated with the parallel inhibition of biochemical, cytogenetic and histopathological alterations as well as with inhibition of preneoplastic and neoplastic lesions in rodents. Our working hypothesis is that DNA adducts in trachea/lung, heart and aorta may be associated with lung cancer, cardiomyopathies and atherosclerosis, respectively. DNA adducts were consistently detectable in the DNA of smooth muscle cells from abdominal aorta specimens taken at surgery from atherosclerotic patients. Even broader are the consequences of mitochondrial (mt) DNA impairment, which has been associated with aging, cancer, and other degenerative diseases. Our data show that adduct levels are consistently higher in mtDNA than in the nuclear DNA in different organs of rats exposed either to benzo[a]pyrene, 2-acetylaminofluorene or cigarette smoke. NAC significantly decreased the formation of adducts to mtDNA when administered with drinking-water. Inhibition of adducts to nuclear DNA is one of the end points evaluated in ongoing Phase II chemoprevention trials in high-risk individuals.

Hyperdynamic circulation of advanced cirrhosis: a re-appraisal based on posture-induced changes in hemodynamics.

Little is known about the effect of posture on the circulatory abnormalities of advanced cirrhosis. We evaluated the systemic hemodynamics, measured by Doppler-echocardiography, atrial natriuretic factor, plasma renin activity and plasma norepinephrine, in 10 patients with cirrhosis and ascites and 10 healthy controls, after 2 h of standing and during lying down for a further 2 h. Standing hemodynamic patterns of controls and patients with cirrhosis did not differ significantly. The latter, however, showed higher plasma renin activity, norepinephrine and atrial natriuretic factor. The assumption of the supine position led to greater increases in cardiac index and atrial natriuretic factor, and reduction in systemic vascular resistance in patients with cirrhosis. Norepinephrine and plasma renin activity declined in both groups to a similar extent, while heart rate only slowed in controls. Thus, after 2 h in the supine position, patients with cirrhosis showed hyperdynamic circulation with increased cardiac index and heart rate and reduced systemic vascular resistance. Norepinephrine, plasma renin activity and atrial natriuretic factor were also elevated. The hyperdynamic circulation in advanced cirrhosis appears during or is enhanced by lying down. This finding suggests that this syndrome is, at least in part, attributable to excessive blood volume translocation towards the central area. However, the persistent activation of renin-angiotensin and sympathoadrenergic systems suggests that a concomitant reduced vascular sensitivity to vasoconstrictors concurs in its development.

Renal sodium handling in cirrhosis with ascites: mechanisms of impaired natriuretic response to reclining.

We recently showed that patients with compensated cirrhosis can dispose of their fluid overload while reclining. In contrast, patients with ascites fail to develop supine-induced natriuresis. To assess the effect of reclining on renal sodium handling in patients with advanced cirrhosis and the mechanisms blunting natriuresis in this situation, renal function and plasma concentrations of atrial natriuretic factor, aldosterone and norepinephrine were evaluated in 10 nonazotemic patients with cirrhosis and ascites and 10 healthy controls standing for 2 h and reclining for 2 h. While standing, all patients showed marked sodium retention and significantly elevated plasma atrial natriuretic factor levels, aldosterone and norepinephrine. Glomerular filtration rate did not differ from healthy controls. The reclining increased renal sodium excretion in both groups, but this change was far less marked in patients; natriuresis only rose to the control range in two of them. An increase in atrial natriuretic factor and a depression of plasma aldosterone and norepinephrine was seen in both controls and patients. In the latter, despite the greater change in atrial natriuretic factor and aldosterone, the aldosterone to atrial natriuretic factor ratio, which was inversely correlated with natriuresis during both standing and reclining remained significantly elevated. In the two patients who achieved normal natriuresis during reclining, reclining was associated with both the normalization of the aldosterone/atrial natriuretic factor ratio, and with an increase in glomerular filtration rate. The supine-induced increase in atrial natriuretic factor was not only preserved but was even enhanced in cirrhosis with ascites.(ABSTRACT TRUNCATED AT 250 WORDS)

Detection of p53 and histopathological classification of skin tumours induced by halogen lamps in hairless mice.

Skin lesions induced by exposure of three strains of female hairless mice to the light emitted by uncovered halogen quartz lamps were subjected to histopathological analysis. We examined 170 representative specimens out of a total of 597 skin lesions, i.e. 38 out of 74 SKH-1 mice, 110 out of 472 MF-1 mice, and 42 out of 51 C3H mice. The results provided evidence of various types of alterations, including preneoplastic changes, such as epidermal hyperplasia, and benign tumours, such as papillomas, as well as tumours with an increasing degree of malignancy, i.e., keratoacanthoma-like tumours, appendage/basal tumours, actinic keratoses/carcinomas in situ, and squamocellular carcinomas. SKH-1 was the most sensitive strain to the far-ultraviolet wavelengths delivered by halogen lamps, as shown not only by the shortest latency time and the highest multiplicity of skin lesions but also by the highest frequency of malignant tumours. Some areas of atypical melanocyte proliferation were only detected in C3H pigmented mice. Eighty-two of the lesions excised from MF-1 mice were additionally examined for p53 protein by immunohistochemical methods. Formalin-fixed, paraffin-embedded sections and frozen sections were analyzed in parallel by using polyclonal CM-1 antibody and monoclonal PAb240 antibody, respectively. A positive response for p53 was only observed in squamocellular carcinomas, and was related to the size of cancers; in fact, six out of 10 cancers of 10-30 mm in diameter were positive, whereas all 16 cancers of 2-9 mm in diameter were negative. All six positive squamocellular carcinomas were detected by using the CM-1 antibody, which recognizes both wild-type and mutant forms of p53 protein, and five of them were also positive with the PAb 240 antibody, which only recognizes the mutant form. Thus, p53 mutation appears to be a late event in the development of halogen-induced skin tumours in hairless mice, requiring a severe degree of malignancy and an advanced stage of the neoplastic mass growth.

Renal sodium retention during upright posture in preascitic cirrhosis.

BACKGROUND: Renal sodium handling in preascitic cirrhosis is not clearly defined. This issue was addressed by evaluating renal sodium metabolism with different postures. METHODS: Renal function and plasma atrial natriuretic factor (ANF), aldosterone, and norepinephrine levels were determined after 2 hours of standing and 30, 60, and 120 minutes after taking up the supine position in 10 patients and 10 healthy subjects. RESULTS: When upright, patients' glomerular filtration rate and plasma ANF and norepinephrine levels did not differ from those of controls. Conversely, renal sodium excretion was reduced. Plasma aldosterone levels, which were slightly elevated, inversely correlated with renal sodium excretion. In the supine position, natriuresis increased by 308% +/- 99% in patients and 113% +/- 29% in controls (P = 0.016), so that it no longer differed between the two groups. Plasma norepinephrine and aldosterone levels decreased to a similar extent in controls and cirrhotics, whereas the increase in plasma ANF level was greater in patients. The changes in natriuresis correlated with those in plasma ANF levels and plasma aldosterone-ANF ratios in both controls and patients. CONCLUSIONS: Aldosterone-dependent sodium retention develops in preascitic cirrhosis during standing. The supine position is the means whereby standing-induced sodium retention can be balanced.

Juvenile myoclonic epilepsy of Janz: clinical observations in 60 patients.

We studied 60 patients with juvenile myoclonic epilepsy (JME). There was a high positive family history for epilepsy (33.3%). Age at onset of epilepsy ranged from 4 to 18 years with an average of 13.9 years. 88.3% of patients were seizure-free. The most effective drug was valproate. In eight patients drug withdrawal was attempted but all patients relapsed during a follow-up period of 1 year. Video-EEG studies were performed in eight newly diagnosed patients; myoclonic jerks were recorded in five patients.