Search

Background: After considerable weight loss, the breast suffers significant deformation. The ptotic breast is characterized by a lack of superior pole, tissue excess in the inferior pole, down-migration of nipple-areola complex (NAC) with redundancy of skin tissue. The authors describe a mastopexy technique based on a modulated and progressive reshaping, back rotation, and suspension of mammary gland parenchyma without parenchymal incisions., Methods: Forty-five patients with bilateral moderate or severe breast ptosis underwent mastopexy from January 2011 to January 2014 with complete detachment of breast from the pectoralis major muscle and the plication of parenchyma without any parenchymal incision. Patients were followed up for one year, reporting any complication, and measuring the jugulum-NAC distance. The outcomes were assessed by the patients as well as the surgical team., Results: The aesthetic outcomes were good or excellent in all patients. The new mammary contour and the distance between the jugular fossa and the nipple were stable during this time with a good filling of upper pole. No major complications were reported., Conclusions: This technique gave good breast shape, long-term projection, and upper pole fullness, without parenchymal incisions. It restores breast shape and projection, especially in post-bariatric patients. A similar technique has not been described yet.

Ketorolac is a powerful non-steroidal anti-inflammatory drug (NSAID), with a great analgesic activity, present on the Italian market since 1991. Despite the excellent therapeutic activity, the chronic use of ketorolac has long been limited owing to the high incidence of gastrointestinal and kidney side events. In our previous study, we demonstrated that ketorolac-galactose conjugate (ketogal), synthesized and tested in a single-dose study, was able to reduce ulcerogenicity, while preserving the high pharmacological efficacy of its parent drug. In this paper, in order to verify the suitability of this compound, for repeated administration, ex vivo experiments on naïve mice were performed. Mice were treated for 5 or 7 days with the highest doses of two drugs (ketorolac 10 mg/kg and ketogal 16.3 mg/kg), and the expression of both gastric COX-1 and PGsyn was evaluated. Results showed that oral ketorolac treatment significantly reduced both enzymes; surprisingly, oral treatment with ketogal did not produce significant variation in the expression of the two constitutive enzymes. Moreover, histological experiments on stomach and kidneys clearly indicated that repeated administration of ketogal induced lower toxicity than ketorolac. At same time, in vivo results clearly showed that both ketorolac and ketogal had a similar therapeutic activity in a model of inflammation and in pain perception. These effects were accompanied by the reduction of enzyme expression such as COX-2 and iNOS, and by the modulation of levels of nuclear NF-κB and cytosolic IκB-α in the inflamed paws. These very encouraging results demonstrate for the first time that ketogal could represent a valid and novel therapeutic alternative to the ketorolac and might pave the way for clinical studies.

Background: The authors want to evaluate the efficacy of fibrillary tabotamp dressing in skin graft-donor site. A comparison was made with Vaseline gauzes. Tabotamp is an absorbable haemostatic product of Ethicon (Johnson and Johnson) obtained by sterile and oxidized regenerated cellulose (Rayon). It is used for mild to moderate bleeding., Materials and Methods: 276 patients were subject to skin graft and divided into two group: Group A and Group B. The donor site of patients in Group A was medicated with fibrillary tabotamp, while the patients of Group B were medicated only with Vaseline gauze. We recorded infection, timing of healing, number of dressing change, the pain felt during and after the dressing change with visual analog scale (VAS) and a questionnaire., Results: Patients allocated in Group A healed faster than the Group B. Questionnaires and VAS analysis showed lower pain felt, lower intake of pain drugs and lower infection rate in the Group A than the Group B. Analysis of coast showed lower dressing change in Group A than the Group B., Conclusion: We believe that the use of tabotamp is a very viable alternative to improve healing.

Background: The high incidence of venous leg ulcers and the difficult to give a complete healing involves in an increase of costs for National Health System. Main therapies to obtain a fast healing are compressive bandages, treatment of abnormal venous flow and in-situ-strategies of wound care. Negative pressure therapy does not conventionally used, because these systems not allow the use of compression bandages. Recently the development of ultraportable devices has improved the compliance and the results., Methods: Ten patients with venous chronic ulcer on the lower extremities were recruited for this study: all patients had venous leg ulcers from at least one year. We treated the patients with autologous partial thickness skin graft and subsequently we applied NANOVA device included in compressive bandage. We used NANOVA for fourteen days and after we made traditional medications. We submitted a questionnaire to evaluate the impact of dressing and NANOVA device in the quality of life of patients., Results: The device contributed to the formation of granulation tissue and increased the success rate of autologous skin graft without limiting mobility of patient. In addition to this, we have been able to perform compression bandages thanks to small size of this device. Eight ulcers healed within 90 days of medication., Conclusions: We believe that ultraportable negative pressure systems are useful devices for treatment of venous leg ulcers because them allows to realize a compressive bandage without mobility limitations.

Despite the effectiveness of combined anti-retroviral therapy, human immunodeficiency virus (HIV) infected-patients frequently report diarrhea and neuropsychological deficits. It is claimed that the viral HIV-1 Trans activating factor (HIV-1 Tat) protein is responsible for both diarrhea and neurotoxic effects, but the underlying mechanisms are not known. We hypothesize that colonic application of HIV-1 Tat activates glial cells of the enteric nervous system (EGCs), leading to a neuroinflammatory response able to propagate to the central nervous system. We demonstrated that HIV-1 Tat-induced diarrhea was associated with a significant activation of glial cells within the colonic wall, the spinal cord and the frontal cortex, and caused a consistent impairment of the cognitive performances. The inhibition of glial cells activity by lidocaine, completely abolished the above-described effects. These observations point out the role of glial cells as putative effectors in HIV-1 Tat-associated gastrointestinal and neurological manifestations and key regulators of gut-brain signaling.

Background: Micro-inflammation and changes in gut microbiota may play a role in the pathogenesis of diverticular disease (DD)., Objective: The objective of this article is to evaluate the expression of nitric oxide (NO)-related mediators and S100B in colonic mucosa of patients with DD in an ex vivo model of bacterial infection., Methods: Intestinal biopsies obtained from patients with diverticulosis, symptomatic uncomplicated diverticular disease (SUDD) and SUDD with previous acute diverticulitis (SUDD+AD) were stimulated with the probiotic L. casei DG® (LCDG) and/or the pathogen enteroinvasive Escherichia coli (EIEC). S100B, NO release and iNOS expression were then evaluated., Results: Basal iNOS expression was significantly increased in SUDD and SUDD+AD patients. Basal NO expression was significantly increased in SUDD+AD. No differences in S100B release were found. In all groups, iNOS expression was significantly increased by EIEC and reduced by LCDG. In all groups, except for SUDD+AD, EIEC significantly increased NO release, whereas no increase was observed when LCDG was added to biopsies. EIEC did not induce significant changes in S100B release., Conclusions: Colonic mucosa of patients with DD is characterized by a different reactivity toward pathogenic stimuli. LCDG plays a role in counteracting the pro-inflammatory effects exerted by EIEC, suggesting a beneficial role of this probiotic in DD.

Management of diverticular disease has significantly improved in the last decade. Antibiotic treatment is used for symptom relief and prevention of complications. In Italy, the non-absorbable antibiotic rifaximin is one of the most frequently used drugs, and it is perceived as the reference drug to treat symptomatic diverticular disease. Its non-systemic absorption and high faecal concentrations have oriented rifaximin use to the gastrointestinal tract, where rifaximin exerts eubiotic effects representing an additional value to its antibiotic activity. This position paper was commissioned by the Italian Society of Gastroenterology governing board for a panel of experts (RC, GB, BA) to highlight the indications for treatment of diverticular disease. There is a lack of rationale for drug use for the primary prevention of diverticulitis in patients with diverticulosis; thus, rifaximin use should be avoided. The cyclic use of rifaximin, in association with high-fibre intake, is safe and useful for the treatment of symptomatic uncomplicated diverticular disease, even if the cost-efficacy of long-term treatment remains to be determined. The use of rifaximin in the prevention of diverticulitis recurrence is promising, but the low therapeutic advantage needs to be verified. No evidence is available on the efficacy of rifaximin treatment on acute uncomplicated diverticulitis., (Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: Symptomatic uncomplicated diverticular disease (SUDD) is one of the possible clinical manifestations of diverticular disease. It is a common disorder characterized by chronic abdominal symptoms ranging from lower left abdominal pain to alteration of bowel habit, that significantly reduce quality of life of subject affected. The present article aims to review the current data for medical management of SUDD., Evidence Acquisition: We analyzed the existing literature on the factors involved in the pathogenesis of SUDD and we highlighted the possible target for treatment. Treatment for SUDD should be direct to relieve chronic symptoms and prevent diverticulitis and its complications. In particular we focused on the role of probiotics, fiber-diet, mesalazine and rifaximin on these two aspects. In this setting, we conducted a PubMed search for guidelines, systematic reviews and meta-analyses and updated information to October 2016., Evidence Synthesis: Each topic was evaluated according to the best evidences available. Best results seemed to be obtained with combined therapies and in particular with rifaximin associated to high fiber-diet. This regimen seems to guarantee better symptoms control compared to fiber alone and it is more effective in preventing acute diverticulitis. On the contrary, no clear evidences about the efficacy of mesalazine and probiotics are available., Conclusions: The results of the studies available in literature are controversial and debatable, for this reason a clear and defined algorithm for treatment of SUDD has not yet been defined. Further randomized, double-blind, placebo controlled study are necessary.

Extramammary Paget disease (EMPD) is a rare neoplasm. The clinical case of a 55-year-old man with a two-year history of a pruritic, painless erythematous skin rash on the inguinal region and scrotum is described. After a delay due to improper diagnosis and improper treatments, the patient came to the attention of the Division of plastic surgery. He underwent a punch biopsy and the pathology report came back as EMPD. Surgical excision was carried out, and an abdominal advancement cutaneous flap was performed for the defect repair. This is the first description of a reconstruction after surgical removal of inguinal EMPD with a flap of this type and we think that this type of treatment can be useful and reliable for disease localization in the groin area, especially for patients that present an excess of abdominal skin.

Background: Polymorphisms of genes involved in the regulation of the immune response are risk factors for achalasia, but their contribution to disease pathogenesis is unknown. Nitric oxide is involved both in immune function and inhibitory neurotransmission., Objective: The objective of this article is to assess the association and the functional relevance of the CCTTT-inducible nitric oxide synthase ( NOS2 ) gene promoter polymorphism in achalasia., Methods: Genomic DNA was isolated from 181 achalasia patients and 220 controls. Genotyping of the (CCTTT)n repeats was performed by PCR and capillary electrophoresis, and data analyzed by considering the frequency of the different alleles. HT29 cells were transfected with iNOS luciferase promoter-reporter plasmids containing different (CCTTT)n., Results: The alleles' distribution ranged from 7 to 18, with a peak frequency at 12 repeats. Analysis of the allele frequencies revealed that individuals carrying 10 and 13 CCTTT repeats were respectively less and more frequent in achalasia (OR 0.5, 95% CI 0.3-0.5 and OR 1.6, 95% CI 1-2.4, all p  < 0.05). Long repeats were also significantly associated with an earlier onset of the disease (OR 1.69, 95% CI 1.13-2.53, p  = 0.01). Transfection experiments revealed a similar allele-specific iNOS transcriptional activity., Conclusion: The functional polymorphism (CCTTT) of NOS2 promoter is associated with achalasia, likely by an allele-specific modulation of nitric oxide production.

Introduction: In patients with gastroesophageal reflux disease (GORD), co-existence of functional dyspepsia (FD) is known to be associated with poor response to proton pump inhibitors (PPIs), but the contribution of specific dyspepsia symptoms has not yet been systematically investigated., Objective: We aimed to characterize the impact of dyspepsia symptoms on response to PPIs in patients with GORD., Methods: The enrolled subjects were consecutive patients with a diagnosis of GORD. All patients underwent a 24 hour pH-impedance test, while on PPI therapy. Patients were divided into two groups, refractory and responders, according to the persistence of GORD symptoms. A standardized questionnaire for FD was also administered to assess presence of dyspepsia symptoms., Results: In the subgroup of refractory patients FD was more prevalent than in responders, with post-prandial fullness, nausea, vomiting, early satiation and epigastric pain being significantly prevalent in refractory GORD patients. In the multivariate analysis only early satiation and vomiting were significantly associated with poor response to PPIs., Conclusion: Co-existence of FD is associated with refractory GORD. We showed that only early satiation and vomiting are risk factors for poor response to therapy with PPIs. Our findings suggest that symptoms of early satiation and vomiting would help to identify the subset of PPI-refractory GORD patients.

Background: Total gastrectomy (TG) is responsible for symptoms or disturbance of alimentary status (changes in body weight, food intake per meal and frequency of meal per day) which, in turn are responsible for weight loss and malnutrition. The study evaluates the gut hormone responses in totally gastrectomized (TG) patients after a liquid meal test., Methods: Twenty total gastrectomized cancer-free patients (12 M, 8 F, 56.4 ± 10.2 years, BMI 21.4 ± 2.2 kg/m2) and 10 healthy volunteers (4 M, 6 F, 48.0 ± 12.7 years, BMI 26.7 ± 3.0 kg/m2 ) drank a liquid meal (1.25 kcal/mL) at the rate of 50 mL/5' min for a maximum of 30 min. Satiety score was assessed and blood sample was taken at different time points., Results: The time response course, particularly for insulin, glucose-like pepetide-1, and cholecystokinin, significantly differed between TG patients and controls., Conclusions: Our results may help to better understand hormone responses triggered by the faster arrival of nutrients in the small bowel and to explain some post-TG symptoms., (© 2017 S. Karger AG, Basel.)

Aim: To evaluate how different levels of adherence to a mediterranean diet (MD) correlate with the onset of functional gastrointestinal disorders., Methods: As many as 1134 subjects (598 M and 536 F; age range 17-83 years) were prospectively investigated in relation to their dietary habits and the presence of functional gastrointestinal symptoms. Patients with relevant chronic organic disease were excluded from the study. The Mediterranean Diet Quality index for children and adolescents (KIDMED) and the Short Mediterranean Diet Questionnaire were administered. All subjects were grouped into five categories according to their ages: 17-24 years; 25-34; 35-49; 50-64; above 64., Results: On the basis of the Rome III criteria, our population consisted of 719 (63.4%) individuals who did not meet the criteria for any functional disorder and were classified as controls (CNT), 172 (13.3%) patients meeting criteria for prevalent irritable bowel syndrome (IBS), and 243 (23.3%) meeting criteria for prevalent functional dyspepsia (FD). A significantly lower adherence score in IBS (0.57 ± 0.23, P < 0.001) and FD (0.56 ± 0.24, P < 0.05) was found compared to CNT (0.62 ± 0.21). Females with FD and IBS exhibited significantly lower adherence scores (respectively 0.58 ± 0.24, P < 0.05 and 0.56 ± 0.22, P < 0.05) whereas males were significantly lower only for FD (0.53 ± 0.25, P < 0.05). Age cluster analyses showed a significantly lower score in the 17-24 years and 25-34 year categories for FD (17-24 years: 0.44 ± 0.21, P < 0.001; 25-34 years: 0.48 ± 0.22, P < 0.05) and IBS (17-24 years: 0.45 ± 0.20, P < 0.05; 24-34 years: 0.44 ± 0.21, P < 0.001) compared to CNT (17-24 years: 0.56 ± 0.21; 25-34 years: 0.69 ± 0.20)., Conclusion: Low adherence to MD may trigger functional gastrointestinal symptoms, mainly in younger subjects. Moreover, with increasing age, patients tend to adopt dietary regimens closer to MD., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report.

Diverticular disease (DD) is a widespread condition, however limited evidences are available about its management and complications. In the last years, an Italian Consensus Conference promoted by GRIMAD (Gruppo Italiano Malattia Diverticolare, Italian Group on Diverticular Diseases) and a Guideline, by Italian Society of Colorectal Surgery (SICCR) were published. The aim of the Consensus was to provide clinical recommendation for appropriate definition, diagnosis, and management of DD, in particular 4 areas of interest were identified, namely: (i) definition and epidemiology, (ii) pathophysiology, (iii) diagnosis, and (iv) medical and surgical treatment. A total of 55 statements graded according to different level of evidence and strength of recommendation were approved. However, if we consider the grade of recommendation, their strength remains suboptimal, with only 3 statements with grade of evidence A in the area of diagnosis. The Clinical guidelines by SICCR focus mainly on acute diverticulitis, and surgical treatment of complicated DD. One of the main topic analyzed, is represented by the management of the acute uncomplicated diverticulitis, in particular about the use of antibiotics and need of hospitalization. Despite the presence of many recent European and western country guidelines, there is a lack of robust data on epidemiology, risk factors, and medical and surgical management of DD, calling the need of further studies aimed to obtain an evidence-based approach in this condition.

Radiation-induced cardiovascular disease (RICVD) is the most common nonmalignant cause of morbidity and mortality among cancer survivors who have undergone mediastinal radiation therapy (RT). Cardiovascular complications include effusive or constrictive pericarditis, cardiomyopathy, valvular heart disease, and coronary/vascular disease. These are pathophysiologically distinct disease entities whose prevalence varies depending on the timing and extent of radiation exposure to the heart and great vessels. Although refinements in RT dosimetry and shielding will inevitably limit future cases of RICVD, the increasing number of long-term cancer survivors, including those treated with older higher-dose RT regimens, will ensure a steady flow of afflicted patients for the foreseeable future. Thus, there is a pressing need for enhanced understanding of the disease mechanisms, and improved detection methods and treatment strategies. Newly characterized mechanisms responsible for the establishment of chronic fibrosis, such as oxidative stress, inflammation and epigenetic modifications, are discussed and linked to potential treatments currently under study. Novel imaging modalities may serve as powerful screening tools in RICVD, and recent research and expert opinion advocating their use is introduced. Data arguing for the aggressive use of percutaneous interventions, such as transcutaneous valve replacement and drug-eluting stents, are examined and considered in the context of prior therapeutic approaches. RICVD and its treatment options are the subject of a rich and dynamic body of research, and patients who are at risk or suffering from this disease will benefit from the care of physicians with specialty expertise in the emerging field of cardio-oncology., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest.

Competing Interests: There are no conflicts of interest.

Feijoa sellowiana fruit has been shown to possess various biological activities, such as anti-bacterial and anti-cancer properties, in a variety of cellular models, but its activity on human intestinal epithelial cells has never been tested. The purpose of this study was to investigate the effects of the acetonic extract of F. sellowiana fruits on the viability, membrane peroxidation, disaccharidases activities and proliferation of in vitro models of human intestinal epithelial cells. To obtain this goal, Caco-2 and HT-29 cells were exposed to the acetonic extract for 24 h. Cell proliferation, viability, lactase and sucrase-isomaltase activity and H2 O2 -induced membrane lipid peroxidation were tested. We found that, compared to control conditions, the acetonic extract significantly increased lactase and sucrase-isomaltase activity in Caco-2, but not HT-29, cells, decreased proliferation, had no effects on viability and restored lipid peroxidation in both cell models. This study suggests that the acetonic extract improves lactase and sucrase-isomaltase activity, inhibits cell proliferation, have no cytotoxic effects and prevent lipid peroxidation of intestinal epithelial cells. These effects may be exploited in case of disaccharidases deficit and also as an adjuvant treatment of diseases related to oxidative stress. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Activation of intestinal human pregnane X receptor (PXR) has recently been proposed as a promising strategy for the chemoprevention of inflammation-induced colon cancer. The present study was aimed at evaluating the effect of rifaximin, a non-absorbable antibiotic, in inhibiting angiogenesis in a model of human colorectal epithelium and investigating the role of PXR in its mechanism of action. Caco-2 cells were treated with rifaximin (0.1, 1.0 and 10.0 µM) in the presence or absence of ketoconazole (10 µM) and assessed for cell proliferation, migration and expression of proliferating cell nuclear antigen (PCNA). The release of vascular endothelial growth factor (VEGF) and nitric oxide (NO), expression of Akt, mechanistic target of rapamycin (mTOR), p38 mitogen activated protein kinases (MAPK), nuclear factor κB (NF-κB) and metalloproteinase-2 and -9 (MMP-2 and -9) were also evaluated. Treatment with rifaximin 0.1, 1.0 and 10.0 µM caused significant and concentration-dependent reduction of cell proliferation, cell migration and PCNA expression in the Caco-2 cells vs. untreated cells. Treatment downregulated VEGF secretion, NO release, VEGFR-2 expression, MMP-2 and MMP-9 expression vs. untreated cells. Rifaximin treatment also resulted in a concentration-dependent decrease in the phosphorylation of Akt, mTOR, p38MAPK and inhibition of hypoxia-inducible factor 1-α (HIF-1α), p70S6K and NF-κB. Ketoconazole (PXR antagonist) treatment inhibited these effects. These findings demonstrated that rifaximin causes PXR-mediated inhibition of angiogenic factors in Caco-2 cell line and may be a promising anticancer tool.

Background: Clinical observations or animal studies implicate enteric glial cells in motility disorders, irritable bowel syndrome, inflammatory bowel disease, gastrointestinal (GI) infections, postoperative ileus, and slow transit constipation. Mechanisms underlying glial responses to inflammation in human GI tract are not understood. Our goal was to identify the "reactive human enteric glial cell (rhEGC) phenotype" induced by inflammation, and probe its functional relevance., Methods: Human enteric glial cells in culture from 15 GI-surgical specimens were used to study gene expression, Ca, and purinergic signaling by Ca/fluo-4 imaging and mechanosensitivity. A nanostring panel of 107 genes was designed as a read out of inflammation, transcription, purinergic signaling, vesicular transport protein, channel, antioxidant, and other pathways. A 24-hour treatment with lipopolysaccharide (200 μg/mL) and interferon-γ (10 μg/mL) was used to induce inflammation and study molecular signaling, flow-dependent Ca responses from 3 mL/min to 10 mL/min, adenosine triphosphate (ATP) release, and ATP responses., Results: Treatment induced a "rhEGC phenotype" and caused up-regulation in messenger RNA transcripts of 58% of 107 genes analyzed. Regulated genes included inflammatory genes (54%/IP10; IFN-γ; CxCl2; CCL3; CCL2; C3; s100B; IL-1β; IL-2R; TNF-α; IL-4; IL-6; IL-8; IL-10; IL-12A; IL-17A; IL-22; and IL-33), purine-genes (52%/AdoR2A; AdoR2B; P2RY1; P2RY2; P2RY6; P2RX3; P2RX7; AMPD3; ENTPD2; ENTPD3; and NADSYN1), channels (40%/Panx1; CHRNA7; TRPV1; and TRPA1), vesicular transporters (SYT1, SYT2, SNAP25, and SYP), transcription factors (relA/relB, SOCS3, STAT3, GATA&#95;3, and FOXP3), growth factors (IGFBP5 and GMCSF), antioxidant genes (SOD2 and HMOX1), and enzymes (NOS2; TPH2; and CASP3) (P < 0.0001). Treatment disrupted Ca signaling, ATP, and mechanical/flow-dependent Ca responses in human enteric glial cells. ATP release increased 5-fold and s100B decreased 33%., Conclusions: The "rhEGC phenotype" is identified by a complex cascade of pro-inflammatory pathways leading to alterations of important molecular and functional signaling pathways (Ca, purinergic, and mechanosensory) that could disrupt GI motility. Inflammation induced a "purinergic switch" from ATP to adenosine diphosphate/adenosine/uridine triphosphate signaling. Findings have implications for GI infection, inflammatory bowel disease, postoperative ileus, motility, and GI disorders., Competing Interests: and The authors have declared that no conflict of interest exists.

Idiopathic achalasia is a severe motility disorder of the esophagus and is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. Most recently, we identified an eight-amino-acid insertion in the cytoplasmic tail of HLA-DQβ1 as strong achalasia risk factor in a sample set from Central Europe, Italy and Spain. Here, we tested whether the HLA-DQβ1 insertion also confers achalasia risk in the Polish and Swedish population. We could replicate the initial findings and the insertion shows strong achalasia association in both samples (Poland P=1.84 × 10(-04), Sweden P=7.44 × 10(-05)). Combining all five European data sets - Central Europe, Italy, Spain, Poland and Sweden - the insertion is achalasia associated with Pcombined=1.67 × 10(-35). In addition, we observe that the frequency of the insertion shows a geospatial north-south gradient. The insertion is less common in northern (around 6-7% in patients and 2% in controls from Sweden and Poland) compared with southern Europeans (~16% in patients and 8% in controls from Italy) and shows a stronger attributable risk in the southern European population. Our study provides evidence that the prevalence of achalasia may differ between populations.

Background/aim: Since their introduction in 1991, propeller flaps are increasingly used as a surgical approach to loss of substance. The aim of this study was to evaluate the indications and to verify the outcomes and the complication rates using this reconstructing technique through a literature review., Materials and Methods: A search on PubMed was performed using "propeller flap", "fasciocutaneous flap", "local flap" or "pedicled flap" as key words. We selected clinical studies using propeller flaps as a reconstructing technique., Results: We found 119 studies from 1991 to 2015. Overall, 1,315 propeller flaps were reported in 1,242 patients. Most frequent indications included loss of substance following tumor excision, repair of trauma-induced injuries, burn scar contractures, pressure sores and chronic infections. Complications were observed in 281/1242 patients (22.6%) occurring more frequently in the lower limbs (31.8%). Partial flap necrosis and venous congestion were the most frequent complications. The complications' rate was significantly higher in infants (<10 years old) and in the older population (>70 years old) but there was not a significant difference between the sexes. Trend of complication rate has not improved during the last years., Conclusion: Propeller flaps showed a great success rate with low morbidity, quick recovery, good aesthetic outcomes and reduced cost. The quality and volume of the transferred soft tissue, the scar orientation and the possibility of direct donor site closure should be considered in order to avoid complications. Indications for propeller flaps are small- or medium-sized defects located in a well-vascularized area with healthy surrounding tissues., (Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: The main application of hyaluronic acid filling, in esthetic medicine, is the augmentation of soft tissues. The carbon dioxide therapy, instead, improves quality and elasticity of the dermis and increases the oxygen release to the tissue through an enhancing of the Bohr's effect. The aim of the study was to compare the efficacy, tolerability, and effect duration of hyaluronic acid fillers and the use of carbon dioxide therapy plus hyaluronic acid in the cosmetic correction of nasolabial folds., Materials and Methods: Forty healthy female patients received a blinded and randomized treatment on nasolabial folds (hyaluronic acid in group A and hyaluronic acid plus subcutaneous injections of carbon dioxide in group B) for cosmetic correction of the nasolabial folds. The results were evaluated by two blinded plastic surgeons after the implant (1 week, 4 and 6 months) using a 1-5 graduated scale (GAIS), and at the same time, each patient was asked to express her opinion about the cosmetic result., Results: Any long-term adverse reaction was reported. The blinded evaluation at 4 and 6 months from the implant shows in all patients a maintenance of a good cosmetic result higher for the side treated with carbon dioxide therapy plus hyaluronic acid., Conclusions: At the control visit, 6 months after the treatment, the patients treated with hyaluronic acid plus carbon dioxide therapy maintain a satisfactory esthetic result while the nasolabial fold treated only with hyaluronic acid shows, in almost all patients, a come back to pretreatment appearance., (© 2016 Wiley Periodicals, Inc.)

Palmitoylethanolamide (PEA) is a nutraceutical compound that has been demonstrated to improve intestinal inflammation. We aimed at evaluating its antiproliferative and antiangiogenic effects in human colon adenocarcinoma Caco-2 cell line. Caco-2 cells were treated with increasing concentrations of PEA (0.001, 0.01 and 0.1 μM) in the presence of peroxisome proliferator-activated receptor-a (PPAR-α) or PPAR-γ antagonists. Cell proliferation was evaluated by performing a MTT assay. Vascular endothelial growth factor (VEGF) release was estimated by ELISA, while the expression of VEGF receptor and the activation of the Akt/mammalian target of rapamycin (mTOR) pathway were evaluated by western blot analysis. PEA caused a significant and concentration-dependent decrease of Caco-2 cell proliferation at 48 h. PEA administration significantly reduced in a concentration-dependent manner VEGF secretion and VEGF receptor expression. Inhibition of Akt phosphorylation and a downstream decrease of phospho-mTOR and of p-p70S6K were observed as compared with untreated cells. PPAR-α, but not PPAR-γ antagonist, reverted all effects of PEA. PEA is able to decrease cell proliferation and angiogenesis. The antiangiogenic effect of PEA depends on the specific inhibition of the AkT/mTOR axis, through the activation of PPAR-α pathway. If supported by in vivo models, our data pave the way to PEA co-administration to the current chemotherapeutic regimens for colon carcinoma. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background and Aim: Angiogenesis is emerging as a pivotal process in chronic inflammatory pathologies, promoting immune infiltration and prompting carcinogenesis. Ulcerative Colitis (UC) and Crohn's Disease (CD) represent paradigmatic examples of intestinal chronic inflammatory conditions in which the process of neovascularization correlates with the severity and progression of the diseases. Molecules able to target the angiogenesis have thus the potential to synergistically affect the disease course. Beyond its anti-inflammatory effect, palmitoylethanolamide (PEA) is able to reduce angiogenesis in several chronic inflammatory conditions, but no data about its anti-angiogenic activity in colitis have been produced, yet., Methods: The effects of PEA on inflammation-associated angiogenesis in mice with dextran sulphate sodium (DSS)-induced colitis and in patients with UC were assessed. The release of Vascular Endothelial Growth Factor (VEGF), the hemoglobin tissue content, the expression of CD31 and of phosphatidylinositol 3-kinase/Akt/mammalian-target-of-rapamycin (mTOR) signaling axis were all evaluated in the presence of different concentrations of PEA and concomitant administration of PPAR-α and -γ antagonists., Results: Our results demonstrated that PEA, in a selective peroxisome proliferator activated receptor (PPAR)-α dependent mechanism, inhibits colitis-associated angiogenesis, decreasing VEGF release and new vessels formation. Furthermore, we demonstrated that the mTOR/Akt axis regulates, at least partly, the angiogenic process in IBD and that PEA directly affects this pathway., Conclusions: Our results suggest that PEA may improve inflammation-driven angiogenesis in colonic mucosa, thus reducing the mucosal damage and potentially affecting disease progression and the shift towards the carcinogenesis.

Background: Clostridium difficile infections (CDIs) caused by Clostridium difficile toxin A (TcdA) lead to severe ulceration, inflammation and bleeding of the colon, and are difficult to treat., Aim: The study aimed to evaluate the effect of rifaximin on TcdA-induced apoptosis in intestinal epithelial cells and investigate the role of PXR in its mechanism of action., Methods: Caco-2 cells were incubated with TcdA and treated with rifaximin (0.1-10 μM) with or without ketoconazole (10 μM). The transepithelial electrical resistance (TEER) and viability of the treated cells was determined. Also, the expression of zona occludens-1 (ZO-1), toll-like receptor 4 (TLR4), Bcl-2-associated X protein (Bax), transforming growth factor-β-activated kinase-1 (TAK1), myeloid differentiation factor 88 (MyD88), and nuclear factor-kappaB (NF-κB) was determined., Results: Rifaximin treatment (0.1, 1.0, and 10 μM) caused a significant and concentration-dependent increase in the TEER of Caco-2 cells (360, 480, and 680% vs. TcdA treatment) 24 h after the treatment and improved their viability (61, 79, and 105%). Treatment also concentration-dependently decreased the expression of Bax protein (-29, -65, and -77%) and increased the expression of ZO-1 (25, 54, and 87%) and occludin (71, 114, and 262%) versus TcdA treatment. The expression of TLR4 (-33, -50, and -75%), MyD88 (-29, -60, and -81%) and TAK1 (-37, -63, and -79%) were also reduced with rifaximin versus TcdA treatment. Ketoconazole treatment inhibited these effects., Conclusion: Rifaximin improved TcdA-induced toxicity in Caco-2 cells by the PXR-dependent TLR4/MyD88/NF-κB pathway mechanism, and may be useful in the treatment of CDIs.

Many techniques for nipple-areola complex (NAC) reconstruction are described. Clarity is required on the currently available options. Since a complete list of all the techniques described until now is not available, a possibly comprehensive literature overview was carried out from 75 papers (years 1946-2015). The local flap was the most frequently described technique for the nipple reconstruction with no significant difference in complications' rate among the various types of techniques. Complications in nipple reconstruction were 46.9% after graft, 7.9% after local flap, and 5.3% in case of flaps with autologous graft/alloplastic/allograft augmentation, while complications in areola reconstruction were 10.1% after graft, and 1.6% after areola tattoo. Flaps appear to be more reliable than grafts in nipple reconstruction, while tattoo is thought to be safer than graft in areola reconstruction. The loss of projection, although considerable (45%-75%), had not significant impact on patients' satisfaction. Due to contraction, overcorrection of 25-50% of the desired result is advisory when adopting local flaps, in order to prevent loss of projection. The use of flaps with autologous graft/alloplastic/allograft augmentation (cartilage, fat, calcium hydroxylapatite, acellular dermal matrix, polymethylmethacrylate, biologic collagen) showed a minor loss of nipple projection but may expose to a relative increased number of postoperative flap necrosis., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Alzheimer's disease (AD) is characterized by chronic deposition of β-amyloid (Aβ) in the brain, progressive neurodegeneration and consequent cognitive and behavioral deficits that typify the disease. Astrocytes are pivotal in this process because they are activated in the attempt to digest Aβ which starts a neuroinflammatory response that further contributes to neurodegeneration. The intestine is a good source of astrocytes-like cells-referred to as enteric glial cells (EGCs). Here we show that the autologous transplantation of EGCs into the brain of Aβ-injected rats arrested the development of the disease after their engraftment. Transplanted EGCs showed anti-amyloidogenic activity, embanked Aβ-induced neuroinflammation and neurodegeneration, and released neutrophic factors. The overall result was the amelioration of the pathological hallmarks and the cognitive and behavioral deficits typical of Aβ-associated disease. Our data indicate that autologous EGCs transplantation may provide an efficient alternative for applications in cell-replacement therapies to treat neurodegeneration in AD.

The word "glia" is derived from the Greek word "γλoια," glue of the enteric nervous system, and for many years, enteric glial cells (EGCs) were believed to provide mainly structural support. However, EGCs as astrocytes in the central nervous system may serve a much more vital and active role in the enteric nervous system, and in homeostatic regulation of gastrointestinal functions. The emphasis of this review will be on emerging concepts supported by basic, translational, and/or clinical studies, implicating EGCs in neuron-to-glial (neuroglial) communication, motility, interactions with other cells in the gut microenvironment, infection, and inflammatory bowel diseases. The concept of the "reactive glial phenotype" is explored as it relates to inflammatory bowel diseases, bacterial and viral infections, postoperative ileus, functional gastrointestinal disorders, and motility disorders. The main theme of this review is that EGCs are emerging as a new frontier in neurogastroenterology and a potential therapeutic target. New technological innovations in neuroimaging techniques are facilitating progress in the field, and an update is provided on exciting new translational studies. Gaps in our knowledge are discussed for further research. Restoring normal EGC function may prove to be an efficient strategy to dampen inflammation. Probiotics, palmitoylethanolamide (peroxisome proliferator-activated receptor-α), interleukin-1 antagonists (anakinra), and interventions acting on nitric oxide, receptor for advanced glycation end products, S100B, or purinergic signaling pathways are relevant clinical targets on EGCs with therapeutic potential.

Social isolation and exclusion are associated with poor health status and premature death. A number of related isolation factors, inadequate transportation system and restrictions in individuals' life space, have been associated with malnutrition in older adults. Since eating is a social event, isolation can have a negative effect on nutrition. Cultural involvement and participation in interactive activities are essential tools to fight social isolation, and they can counteract the detrimental effects of social isolation on health. To provide data supporting the hypothesis that encouraging participation might represent an innovative preventive and health promoting strategy for healthy living and aging, we developed an ad hoc questionnaire to investigate the relationship between cultural participation, well-being, and resilience in a sample of residents in the metropolitan area of Naples. The questionnaire includes a question on adherence to diet or to a special nutritional regimen; in addition, the participants are asked to mention their height and weight. We investigated the relationship between BMI, adherence to diet, and perceived well-being (PWB) and resilience in a sample of 571 subjects over 60 years of age. Here, we present evidence that engagement into social and cultural activities is associated with higher well-being and resilience, in particular in females over 60 years of age.

Objective: Low-grade intestinal inflammation plays a role in the pathophysiology of IBS. In this trial, we aimed at evaluating the efficacy and safety of mesalazine in patients with IBS., Design: We conducted a phase 3, multicentre, tertiary setting, randomised, double-blind, placebo-controlled trial in patients with Rome III confirmed IBS. Patients were randomly assigned to either mesalazine, 800 mg, or placebo, three times daily for 12 weeks, and were followed for additional 12 weeks. The primary efficacy endpoint was satisfactory relief of abdominal pain/discomfort for at least half of the weeks of the treatment period. The key secondary endpoint was satisfactory relief of overall IBS symptoms. Supportive analyses were also performed classifying as responders patients with a percentage of affirmative answers of at least 75% or >75% of time., Results: A total of 185 patients with IBS were enrolled from 21 centres. For the primary endpoint, the responder patients were 68.6% in the mesalazine group versus 67.4% in the placebo group (p=0.870; 95% CI -12.8 to 15.1). In explorative analyses, with the 75% rule or >75% rule, the percentage of responders was greater in the mesalazine group with a difference over placebo of 11.6% (p=0.115; 95% CI -2.7% to 26.0%) and 5.9% (p=0.404; 95% CI -7.8% to 19.4%), respectively, although these differences were not significant. For the key secondary endpoint, overall symptoms improved in the mesalazine group and reached a significant difference of 15.1% versus placebo (p=0.032; 95% CI 1.5% to 28.7%) with the >75% rule., Conclusions: Mesalazine treatment was not superior than placebo on the study primary endpoint. However, a subgroup of patients with IBS showed a sustained therapy response and benefits from a mesalazine therapy., Trial Registration Number: ClincialTrials.gov number, NCT00626288., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Youth and adolescent non-medical use of prescription medications (NUPM) has become a national epidemic. However, little is known about the association between promotion of NUPM behavior and access via the popular social media microblogging site, Twitter, which is currently used by a third of all teens., Objective: In order to better assess NUPM behavior online, this study conducts surveillance and analysis of Twitter data to characterize the frequency of NUPM-related tweets and also identifies illegal access to drugs of abuse via online pharmacies., Methods: Tweets were collected over a 2-week period from April 1-14, 2015, by applying NUPM keyword filters for both generic/chemical and street names associated with drugs of abuse using the Twitter public streaming application programming interface. Tweets were then analyzed for relevance to NUPM and whether they promoted illegal online access to prescription drugs using a protocol of content coding and supervised machine learning., Results: A total of 2,417,662 tweets were collected and analyzed for this study. Tweets filtered for generic drugs names comprised 232,108 tweets, including 22,174 unique associated uniform resource locators (URLs), and 2,185,554 tweets (376,304 unique URLs) filtered for street names. Applying an iterative process of manual content coding and supervised machine learning, 81.72% of the generic and 12.28% of the street NUPM datasets were predicted as having content relevant to NUPM respectively. By examining hyperlinks associated with NUPM relevant content for the generic Twitter dataset, we discovered that 75.72% of the tweets with URLs included a hyperlink to an online marketing affiliate that directly linked to an illicit online pharmacy advertising the sale of Valium without a prescription., Conclusions: This study examined the association between Twitter content, NUPM behavior promotion, and online access to drugs using a broad set of prescription drug keywords. Initial results are concerning, as our study found over 45,000 tweets that directly promoted NUPM by providing a URL that actively marketed the illegal online sale of prescription drugs of abuse. Additional research is needed to further establish the link between Twitter content and NUPM, as well as to help inform future technology-based tools, online health promotion activities, and public policy to combat NUPM online.

Objective: The purposes of this study was to assess the effect of repeated subcutaneous injections of CO2 on adipose tissue graft survival in immunosuppressed female nude mice. The authors designed an experimental study using volume measures, histopathological analysis and nuclear magnetic resonance of fat graft. The effect of repeated subcutaneous injection of CO2 is not yet investigated, Materials and Methods: Approximately 0.5 ml of human fat were transplanted in a group of female nude mice. The mice were treated with 3 injections of 80 µl each carbon dioxide (total 240 µl) for 7 weeks. Initially, in vivo measurements were conducted and subsequently a comprehensive histopathological analysis was performed., Results: The presence of inflammation was graded absent to minimal in animals treated with CO2 while a minimal to moderate grade was assigned to the control group., Conclusions: CO2 injection enhances the inflammatory response of the implanted tissue and reduces the reabsorption rate. The treatment may improve the graft survival in a more prolonged time-frame.

Eosinophilic esophagitis (EoE) is a chronic immune disease, characterized by a dense eosinophilic infiltrate in the esophagus, leading to bolus impaction and reflux-like symptoms. Traditionally considered a pediatric disease, the number of adult patients with EoE is continuously increasing, with a relatively higher incidence in western countries. Dysphagia and food impaction represent the main symptoms complained by patients, but gastroesophageal reflux-like symptoms may also be present. Esophageal biopsies are mandatory for the diagnosis of EoE, though clinical manifestations and proton pump inhibitors responsiveness must be taken into consideration. The higher prevalence of EoE in patients suffering from atopic diseases suggests a common background with allergy, however both the etiology and pathophysiology are not completely understood. Elimination diets are considered the first-line therapy in children, but this approach appears less effective in adults patients, who often require steroids; despite medical treatments, EoE is complicated in some cases by esophageal stricture and stenosis, that require additional endoscopic treatments. This review summarizes the evidence on EoE pathophysiology and illustrates the safety and efficacy of the most recent medical and endoscopic treatments.

Aim: The purpose of the present study was to analyze the use of autologous dermis compared to non-biological meshes in repair of abdominal wall defects in patients with redundant skin and immunosuppression., Patients and Methods: Eighteen patients with abdominal wall defects, immunosuppression and with redundant skin were divided into two groups: Group A consisted of 11 patients treated with autologous dermis. In these patients, autologous dermis was isolated from the amount of skin resected from the inferior abdominal region that was used as a reinforcement of fascial margins above the defect. Group B consisted of seven patients treated with non-biological meshes We evaluated the infection rate of these groups., Results: The infection rate was significantly lower in group A patients., Conclusion: The transplantation of autologous dermis as a reinforcement for the reconstruction of abdominal wall defects is reasonable for highly selected patients. The use of the dermis was proven useful and we found a lower rate of infection and recurrence., (Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background/aim: Dermolipectomy dramatically improves the quality of life of previously obese patients. Fat removal in patients undergoing liposuction and reduction mammoplasty has positive effects, but no data regarding sequelae of abdominal dermolipectomy on metabolism have been reported. Thus, the aim of the present study was to assess metabolic and biochemical modifications occurring after abdominoplasty. A correlation between the results and the rate of complications was also evaluated., Patients and Methods: One hundred and twenty-eight patients with body mass index (BMI) between 30 and 35 kg/m(2) were enrolled. Clinical assessment, anthropometric measurements, blood biochemical analysis (fasting plasma glucose, total cholesterol, free fatty acids, plasma insulin), plasma adipocytokines (leptin, adiponectin,resistin), levels of inflammatory markers [tumor necrosis factor-alpha (TNFα), interleukin-6 (IL6), C-reactive protein (CRP)] and insulin sensitivity by Homeostasis Model Assessment were performed three times., Results: The average age was 37.6 years. At baseline, the mean (±SD) BMI of patients overall was 33.44 (±2.3) kg/m(2) and the amount of fat surgically removed was 1,578.33 (±1,013.02) g. A significant decrease in BMI at 1 year was found. Adiponectin levels were found to have significantly increased (p<0.05) in long-term evaluation. We noted significant increases in the mean TNFα (p<0.05), IL6 (p<0.01) and CRP (p<0.05), with a return to baseline values of all variables. The majority of patients were satisfied with the surgical procedure after 12 months. We noted a lower rate (10%) of complications in patients whose blood analysis showed an increase of adiponectin., Conclusion: Abdominal dermolipectomy is a safe surgical procedure that improves the quality of life of previously obese patients from an aesthetic functional view. A statistically significant increase of adiponectin after the procedure was found. A low level of adiponectin after surgery indicates a higher probability of complications., (Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background/aims: Bitter taste receptors are expressed throughout the digestive tract. Data on animals have suggested these receptors are involved in the gut hormone release, but no data are available in humans. Our aim is to assess whether bitter agonists influence food intake and gut hormone release in healthy subjects., Methods: Twenty healthy volunteers were enrolled in a double-blind cross-over study. On 2 different days, each subject randomly received an acid-resistant capsule containing either placebo or 18 mg of hydrochloride (HCl) quinine. After 60 minutes, all subjects were allowed to eat an ad libitum meal until satiated. Plasma samples were obtained during the experiment in order to evaluate cholecystokinin (CCK) and ghrelin levels. Each subject was screened to determine phenylthiocarbamide (PTC) tasting status., Results: Calorie intake was significantly lower when subjects received HCl quinine than placebo (514 ± 248 vs 596 ± 286 kcal; P = 0.007). Significantly higher CCK ΔT90 vs T0 and ΔT90 vs T60 were found when subjects received HCl quinine than placebo (0.70 ± 0.69 vs 0.10 ± 0.86 ng/mL, P = 0.026; 0.92 ± 0.75 vs 0.50 ± 0.55 ng/mL, P = 0.033, respectively). PTC tasters ingested a significantly lower amount of calories when they received HCl quinine compared to placebo (526 ± 275 vs 659 ± 320 kcal; P = 0.005), whereas no significant differences were found for PTC non-tasters (499 ± 227 vs 519 ± 231 kcal; P = 0.525)., Conclusions: This study showed that intra-duodenal release of a bitter compound is able to significantly affect calorie intake and CCK release after a standardized meal. Our results suggest that bitter taste receptor signaling may have a crucial role in the control of food intake.

The mission of the Italian Society of Colorectal Surgery (SICCR) is to optimize patient care. Providing evidence-based practice guidelines is therefore of key importance. About the present report it concernes the SICCR practice guidelines for the diagnosis and treatment of diverticular disease of the colon. The guidelines are not intended to define the sole standard of care but to provide evidence-based recommendations regarding the available therapeutic options.

Medial contouring of the thigh is frequently requested to improve appearance and function of medial thigh deformities, following massive weight loss or aging process. This surgical procedure can be associated with a significant rate of complications. Our aim was to consider the complications and outcomes according to the performed technique, through a wide and comprehensive review of the literature. A search on PubMed/Medline was performed using "medial thighplasty", "medial thigh lifting" and "technique" as key words. As inclusion criteria, we selected the clinical studies describing techniques of medial thighplasty. We excluded the papers in which complications related to medial thighplasty were not specified. We also excluded literature-review articles. We found 16 studies from 1988 to 2015. Overall, 447 patients were treated. Different techniques were applied. Complications were observed in 191/447 patients (42.72%). The most frequent complications were wound dehiscence(18.34%) and seroma (8.05%). No major complications, such as thromboembolism and sepsis, were observed. Minor complications occurred in a high percent of patients, regardless of the performed surgical procedure. Patients should be informed about the possible occurrence of wound dehiscence and seroma, as common complications associated with this surgical procedure.

An effective and long-term treatment of cellulite has not been well established. To our knowledge, no review has analyzed the whole range of treatments for this condition. We conducted a review of in vivo studies on humans adopting the key words "cellulite" and "treatment." The studies were included according to eligibility criteria. We performed an analysis to estimate the overall effect of cellulite treatments from clinical studies. Medline library was screened up to December 2014 to identify eligible studies. We included 73 original studies in the present review. All of them were clinical studies, in most of them, only women were recruited. Above the studies searched up, 66 tested the effectiveness of an exclusive treatment performed without the association to other procedures: 11 topical agents, 10 shock-wave therapy, 10 radio frequency, eight laser therapy, five oral therapy, four manual massage therapy, three carbon dioxide therapy, two compressive therapy, two infrared therapy, one dermabrasion, and 11 devices that use an association of multiple treatments. Seven papers tested a combination of two or more treatments. The mean difference of clinical morphologic features and ultrastructural changes between the treated group and the controlled showed significant heterogeneity between studies. It is still difficult to indicate an exclusive and effective single treatment for this condition. Our analysis purposed to obtain a complete overview of the available treatments in cellulite reduction., (© 2015 Wiley Periodicals, Inc.)

Background: Quality of bowel cleansing in hospitalized patients undergoing colonoscopy is often unsatisfactory. No study has investigated the inpatient or outpatient setting as cause of inadequate cleansing., Aims: To assess degree of bowel cleansing in inpatients and outpatients and to identify possible predictors of poor bowel preparation in the two populations., Methods: Prospective multicentre study on consecutive colonoscopies in 25 regional endoscopy units. Univariate and multivariate analysis with odds ratio estimation were performed., Results: Data from 3276 colonoscopies were analyzed (2178 outpatients, 1098 inpatients). Incomplete colonoscopy due to inadequate cleansing was recorded in 369 patients (11.2%). There was no significant difference in bowel cleansing rates between in- and outpatients in both colonic segments. In the overall population, independent predictors of inadequate cleansing both at the level of right and left colon were: male gender (odds ratio, 1.20 [1.02-1.43] and 1.27 [1.05-1.53]), diabetes mellitus (odds ratio, 2.35 [1.68-3.29] and 2.12 [1.47-3.05]), chronic constipation (odds ratio, 1.60 [1.30-1.97] and 1.55 [1.23-1.94]), incomplete purge intake (odds ratio, 2.36 [1.90-2.94] and 2.11 [1.68-2.65]) and a runway time >12h (odds ratio, 3.36 [2.40-4.72] and 2.53 [1.74-3.67])., Conclusions: We found no difference in the rate of inadequate bowel preparation between hospitalized patients and outpatients., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

S100 calcium-binding protein B (S100B) is highly expressed in glioma cells and promotes cancer cell survival via inhibition of the p53 protein. In melanoma cells, this S100B-p53 interaction is known to be inhibited by pentamidine isethionate, an antiprotozoal agent. Thus, the aim of the present study was to evaluate the effect of pentamidine on rat C6 glioma cell proliferation, migration and apoptosis in vitro . The change in C6 cell proliferation following treatment with pentamidine was determined by performing a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide-formazan assay. Significant dose-dependent decreases in proliferation were observed at pentamidine concentrations of 0.05 µM (58.5±5%; P<0.05), 0.5 µM (40.6±7%; P<0.01) and 5 µM (13±4%; P<0.001) compared with the control (100% viability). Furthermore, treatment with 0.05, 0.5 and 5 µM pentamidine was associated with a significant increase in apoptosis versus the untreated cells, as determined by DNA fragmentation assays, immunofluorescence analysis of C6 chromatin using Hoechst staining, and immunoblot analysis of B-cell lymphoma-2 (Bcl-2)-associated X protein (100%, P<0.05; 453%, P<0.01; and 1000%, P<0.001, respectively) and Bcl-2 (-60%, P<0.001; -80.13%, P<0.001; -95%, P<0.001, respectively). In addition, the administration of 0.05, 0.5 and 5 µM pentamidine significantly upregulated the protein expression levels of p53 (681±87.5%, P<0.05; 1244±94.3%, P<0.01; and 2244±111%, P<0.001, respectively), and significantly downregulated the expression levels of matrix metalloproteinase-2 (42±2.3%, P<0.05; 71±2.5%, P<0.01; and 95.8±3.3%, P<0.001, respectively) and aquaporin 4 (38±2.5%, P<0.05; 69±2.6%, P<0.01; and 88±3.0%, P<0.001, respectively), compared with the untreated cells. The wound healing assay demonstrated that cell migration was significantly impaired by treatment with 0.05, 0.5 and 5 µM pentamidine compared with untreated cells (88±4.2%, P<0.05; 64±2%, P<0.01; and 42±3.1%, P<0.001, respectively). Although additional in vivo studies are required to clarify the current in vitro data, the present study indicates that pentamidine and S100B-p53 inhibitors may represent a novel approach for the treatment of glioma.

Objective: In this study the author proposes to compare eutectic mixture of local anesthetics (EMLA) and an odontoiatric spray solution of 10% Lidocaine (Ecocain) for surgical debridement in venous leg ulcers. Approach: Fifty patients were recruited and randomly assigned into two groups (A, B). All of them have venous leg ulcer in the medial and/or lateral malleolar region. Group A: topical anesthetic EMLA with film occlusion. Group B: topical anesthesia with Ecocain. The author proceeded to surgical debridement after local anesthesia. A questionnaire and a visual analog scale (VAS) were administered to assess the amount of pain felt during the debridement and during the following 6 h. Results: The analysis of the VAS revealed no major significant differences statistically. The analysis of the questionnaires showed patients treated with Ecocain took more analgesic drugs. Analysis of the timing and quality of procedure showed that Ecocain reduced the timing of debridement and dressing change, improving the outpatient management and patient compliance. Innovations: For rapid debridement, the most appropriate is to use Ecocain. Conclusion: Methods of local anesthesia are multiple and must be identified according to the needs of the patient and the surgeon trying to get the best anesthesia with minimal use of time and resources.

Three years have passed since the FDA announced that it had detected counterfeit versions of the injectable anticancer drug bevacizumab (Avastin(®), Genentech, USA) in the US drug-supply chain. Following this discovery, almost 1,000 FDA warning letters were sent to physicians and medical practices in 48 different states and two US territories, as more batches of counterfeit Avastin were uncovered. In response, criminal prosecutions have been pursued against certain distributors and clinicians, and other individuals who trafficked, sold, purchased, and/or administered an unsafe and ineffective treatment while also defrauding the government. Although limited and targeted legal action has been taken, patients potentially affected by this seminal patient safety event have not been appropriately identified. Hence, despite the clear and documented patient-safety and public-health risks posed by the transnational criminal trade in counterfeit medicines, the case study of counterfeit bevacizumab detection in the USA demonstrates the continued lack of information, knowledge, and solutions that would be necessary to protect those who are most affected--the patients. In response, we call for greater investment in multisector, multistakeholder strategies to enhance surveillance for counterfeit medicines and enable improvements in communication of risk information, to better protect patients with cancer.

Background: There exists a wide variation in the reported incidence of coeliac disease in recent decades. We aimed to evaluate the incidence rate of coeliac diagnoses performed in an Italian region, Campania, between 2011 and 2013 and its variation therein., Methods: All coeliac diagnoses made from 2011 to 2013 and registered within the Campania coeliac disease register (CeliacDB) were identified. Incidence rates were analysed by sex, age and province of residence, with a Poisson model fitted to determine incidence rate ratios., Results: We found 2049 coeliac disease diagnoses registered in the CeliacDB between 2011 and 2013; 1441 of these patients were female (70.4%) and 1059 were aged less than 19 years (51.7%). The overall incidence of coeliac disease in Campania was 11.8 per 100,000 person-years (95% CI 11.3-12.3) during the study period, with marked variation by age [27.4 per 100,000 person-years (95% CI 25.8-29.1) in children under 19 years of age and 7.3 per 100,000 (95% CI 6.8-7.8) in adults] and sex [16.1 per 100,000 person-years in females (95% CI 15.3-16.9) and 7.2 per 100,000 person-years in males (95% CI 6.6-7.8)]. Coeliac disease incidence was roughly similar in Naples, Salerno, Caserta and Avellino, but about half in Benevento. More than 80% of our study population was diagnosed by the combination of positive antitransglutaminase IgA and Marsh 3. More than half of the patients were symptomatic at the time of coeliac disease diagnosis (39.7% had a classical presentation and 21.1% a non-classical one according to the Oslo definition)., Conclusions: Coeliac disease incidence was roughly similar among Campania provinces, except in Benevento where it was about half, probably due to less awareness of coeliac disease in this area. The incidence of coeliac disease in Campania appears to be lower than that reported by most of the previous literature, suggesting the necessity of new coeliac awareness programmes.