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In recent years, the prevalence of large spectrum of gluten-related disorders (GRDs) has increased. Gluten is one of the most widely distributed components of food in both industrialized and developing countries. The main structural protein complex of wheat and its proteins are classified into albumins, salt-soluble globulins, and insoluble prolamins (gliadins and glutenins). Gluten is also included in other cereals, including rye and barley. GRDs can be classified, based on their pathogenic mechanism, into (i) Autoimmune disorders, (ii) Allergic disorders, (iii) No autoimmune, not allergic disorders. Coeliac disease (CD) is an autoimmune disorder that occurs in genetically predisposed individuals who develop an immune reaction to gluten. It affects about 1% of people in most populations. The disease primarily interests the small intestine, but it is characterized by a wide range of clinical presentations, with both intestinal and extra-intestinal symptoms. Wheat allergy (WA) is an adverse immunologic reaction to wheat proteins. In the large field of WA a further classification can be made, distinguishing IgE-dependent WA, triggered by ingestion, inhalation or cutaneous and/or mucosal contact of wheat, and IgE-non-dependent WA. Its prevalence varies depending on the age and region, from 0.4% to 4%. Urticaria and/or angioedema, and anaphylaxis with or without exercise as a trigger, appear typically during childhood, asthma and/or rhinitis (Baker’s asthma) are more common during adulthood. Non-coeliac gluten sensitivity (NCGS) is a condition in which gluten ingestion leads to one or more of a variety of immunological, morphological or symptomatic (both gastrointestinal or extra gastrointestinal) manifestations in people in whom CD has been excluded. It is supposed it’s due to an activated innate immune response.

Objectives The diagnosis of cystic fibrosis related diabetes (CFRD) is not often easy as glucose homeostasis may be influenced by various disease-related conditions such as enteral continuous drip feeding, frequent acute illness, use of systemic corticosteroids and other concomitant medications. Other forms of diabetes should be considered in the diagnostic work-up, particularly in the first decade of life. Case presentation We hereby present the case of a cystic fibrosis 6-year-old female child diagnosed with glucokinase-maturity onset of diabetes of the young (GCK-MODY). The choice of treatment plan was doubtful since GCK-MODY does not usually require insulin treatment, but hyperglycemia could pose a threat to the respiratory tract. After intensive glucose monitoring, we decided to defer pharmacological treatment based on acceptable daily glycemic control. To date, no worsening in her respiratory function has been revealed. Conclusions Recognition of non-CFRD forms of diabetes is fundamental to plan the most suitable treatment and follow-up.

CFTR modulators (CFTRm) were introduced recently but they are already profoundly changing Cystic Fibrosis (CF) landscape. This survey was conducted in 2018 to evaluate how their perception and use evolved in Italy, with focus on factors that could influence physician treatment decisions. Response rate was 75.6% and the majority of physicians (81%) had been working in CF for over 5 years. While traditional parameters such as lung function and nutritional status remain key evaluation criteria in relation to initiation and monitoring of CFTRm, pulmonary exacerbations ranked at least at the same level of importance in both pediatric and adolescent/adult patients homozygous for F508del, as well as those with residual function mutations. Increasing interest is shown for tools that can help detect early manifestations of disease such as Lung Clearance Index and imaging. Patient-related outcomes, such as ability to conduct daily activities, are also deemed relevant in decision to start and continue CFTRm. Physician decision to initiate treatment according to clinical presentation was similar in all groups, showing that more importance was given to severity/instability of disease rather than mutation type or age range. A relatively low percentage of physicians would treat asymptomatic patients, in particular very young or those with residual function mutations, showing reluctance to treat early in some patient groups in the absence of clear manifestations of CF. Increasing experience with CFTRm will allow to gain more long term evidence and will help shape new guidelines.

What is known and objective The off-label use of vedolizumab (VDZ) for inflammatory bowel disease in children is increasing. We report on possibly the first case of VDZ-associated pulmonary manifestations in paediatrics. Case summary This report details the case of a 13-year-old child with ulcerative colitis who was initiated on VDZ due to persistent active disease. After the first three doses, he developed a persistent and productive cough. Microbiological work-up was normal. VDZ discontinuation led to the resolution of symptoms. What is new and conclusion To our knowledge, this is the first case report of VDZ-associated pulmonary manifestations in paediatrics. A direct, pro-inflammatory effect of VDZ has been hypothesized, but further studies are warranted.

COVID-19 vaccination has been rapidly implemented among patients with cancer. We present the case of a patient with high-risk resected cutaneous melanoma, who was a candidate for adjuvant treatment, with postsurgery 18-fluorodeoxyglucose (FDG) PET/computed tomography (CT) scan showing positive axillary lymph nodes after COVID-19 vaccination. This report presents a 50-year-old man with a history of stage IIA cutaneous melanoma. During follow-up, the patient experienced subcutaneous and lymph-node disease progression, documented with 18FDG PET/CT scan. The patient underwent laparoscopic left para-aortic lymphadenectomy and excision of subcutaneous lesion. Histologic examination showed presence of melanoma metastases in 2 lymph nodes out of total 17 excised and neoplastic emboli to the subcutaneous tissue. In view of starting adjuvant nivolumab, the patient underwent CT scan restaging, with evidence of suspect centimetric periaortic and paracaval lymph nodes, which were deemed worthy of 18FDG PET investigation. The 18FDG PET/CT was negative for abdominal hypercaptation, but showed left axillary pathologic lymph nodes. The medical history of the patient revealed that he had received intramuscular Moderna COVID-19 mRNA vaccine in the left deltoid, one week before 18FDG PET examination. Since the patient's clinical examination was negative and suspecting postvaccination false-positive adenopathy, bilateral axillary ultrasound was performed, excluding the presence of pathologic lymph nodes. The patient has started adjuvant treatment with nivolumab, which is currently ongoing. This case demonstrates unexpected findings in response to COVID-19 vaccination in a patient with melanoma. In this specific case, the detection of 18FDG PET hypercaptation could significantly change the patient's management. With growing evidence about the pattern and occurrence of adenopathies after mRNA COVID-19 vaccination, recommendations for scheduling and interpretation of 18FDG PET/CT scans among cancer patients will be implemented, in order to reduce equivocal findings and improve outcomes.

Total proctocolectomy with ileal J-pouch-anorectal anastomosis (IPAA) remains the preferred surgical treatment for ulcerative colitis (UC) in children. Considering the well-known advantages of minimally invasive approach, and its main application for the deep pelvis, robotic surgery may be used in UC reconstructive procedures. The aim of the study is to report our experience with Robotic IPAA in children. Single surgeon experience on Robotic IPAA were prospectively included. Data on patient demographics, surgical details, complications, and length of stay (LOS), were collected. Fifteen patients were included. Median age was 13.2 years, median body weight 45 kg. Median operative time was 240 min. Median LOS was 7 days and mean follow-up time 1 year. No intraoperative complication occurred. Five postoperative complications happened: 3 minors treated conservatively (CD I–II), 2 majors needing reintervention under anesthesia (CD IIIb). No mortality was observed. Our preliminary experience reveals that Robotic IPAA is a safe and feasible option for the surgical treatment of UC in children. A bigger patient sample and a long-term follow-up are needed to confirm our findings.

We propose here a spectroscopic method to diagnose and differentiate inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn&rsquo, s disease (CD) with pediatric onset, in a complete noninvasive way without performing any duodenal biopsy. In particular, the Raman technique was applied to proteic extract from fecal samples in order to achieve information about molecular vibrations that can potentially furnish spectral signatures of cellular modifications occurring as a consequence of specific pathologic conditions. The attention was focused on the investigation of the amide I region, quantitatively accounting the spectral changes in the secondary structures by applying deconvolution and curve-fitting. Inflammation is found to give rise to a significant increasing of the nonreducible (trivalent)/reducible (divalent) cross-linking ratio of the protein network. This parameter revealed an excellent marker in order to distinguish IBD subjects from non-IBD ones, and, among IBD patients, to differentiate between UC and CD. The proposed methodology was validated by statistical analysis using the receiver operating characteristic (ROC) curve.

Background Rome IV criteria for functional gastrointestinal disorders state that children suspected of having Irritable Bowel Syndrome (IBS) with Constipation (IBS-C) should be preliminarily treated for constipation. We aimed at verifying if functional constipation may indeed lead to an erroneous diagnosis of IBS with diarrhea (IBS-D) or IBS with mixed pattern of diarrhea and constipation (IBS-M). Methods We prospectively enrolled in an unblinded fashion 10 and 16 consecutive children referred to our center who met Rome IV criteria for a diagnosis of IBS-D and IBS-M, respectively. Patients who fulfilled criteria for suspect “occult constipation” were then given a bowel cleaning regimen with Polyethylene glycol 3350, re-evaluated at 2 months and followed up for at least 6 months. Sixteen additional patients with IBS with Constipation (IBS-C) referred in the same period served as control. The endpoints were: 1) a decrease of more than 50% in abdominal pain intensity and frequency scores; and 2) for patients with IBS-D and IBS-M: resolution of diarrhea. Results The endpoints were met by 8 (80%) and 14 (87%) of the patients with IBS-D and IBS-M, respectively, with decrease of abdominal pain and resolution of “diarrhea”. The response was not significantly different from that observed in 15 (93%) of the IBS-C control group. Conclusion Acknowledging the limitations of the small number of patients and of the uncontrolled nature of the study, we suggest that a possibly large number of patients labeled as IBS-D or IBS-M may actually simply present functional constipation and should be managed as such.

Background Analyzing the data of the International Register of Open Abdomen (IROA), the feasibility of open abdomen treatment has been demonstrated at every age. This new analysis on the IROA database investigates the risk factors for mortality in elderly patients treated with open abdomen for intra-abdominal infection. Methods Data were derived from the IROA, a prospective observational international cohort study that enrolled patients treated with open abdomen worldwide. A univariate analysis of potential risk factors was performed. Inclusion criteria were patients older than 65 years and treated with open abdomen for intra-abdominal infection. End point was overall mortality, calculated within 30 days after open abdomen management, after 1-month and 1-year follow-up. Results A total of 116 patients was analyzed with mean age of 76 ± 7 years. Definitive closure was achieved in 93 patients (93/116, 80.2%) for a mean open abdomen duration of 5.0 ± 5.0 days. Complicated patients were 101 (101/116, 87.1%) for a total of 201 complications. Overall, 62 out of 116 patients (53.4%) died: 23 patients (23/62, 37.1%) during open abdomen management, 29 patients (46.8%) within 30 days after abdominal closure, 9 patients (14.5%) after 1-month follow-up, and 1 patient (1.6%) after 1-year follow-up. Age did not affect mortality (75 ± 6 years in alive patients versus 77 ± 7 years in dead patients, p = 0.773). Definitive abdominal closure was the most important factor to prevent mortality. Conclusions This study confirmed that age alone cannot be considered a determinant for death, even in elderly patients managed with open abdomen for severe intra-abdominal infection.

Celiac disease (CD) is diagnosed by a combination of specific serology and typical duodenal lesions. The histological confirmation of CD, mandatory in the majority of patients with suspected CD, is based on invasive and poorly tolerated procedures, such as upper gastrointestinal endoscopy. In this study we propose an alternative and non-invasive methodology able to confirm the diagnosis of CD based on the analysis of serum samples using the Raman spectroscopy technique. Three different bands centered at 1650, 1450 and 1003 cm−1 have been considered and the A1450/A1003 and A1650/A1003 ratios have been computed to discriminate between CD and non-CD subjects. The reliability of the methodology was validated by statistical analysis using receiver operating characteristic (ROC) curves. The Youden index was also determined to obtain optimal cut-off points. The obtained results highlighted that the proposed methodology was able to distinguish between CD and non-CD subjects with 98% accuracy. The optimal cut-off points revealed, for both the A1450/A1003 and A1650/A1003 ratios, high values of sensitivity and specificity (&gt, 95.0% and &gt, 92.0% respectively), confirming that Raman spectroscopy may be considered a valid alternative to duodenal biopsy and demonstrates spectral changes in the secondary structures of the protein network.

Background: Open abdomen is the cornerstone of damage control strategies in acute care and trauma surgery. The role of BMI has not been well investigated. The aim of the study was to assess the role of BMI in determining outcomes after open abdomen. Methods: This is an analysis of patients recorded into the International Register of Open Abdomen; patients were classified in two groups according to BMI using a cutoff of 30 kg/m2. The primary outcome was in-hospital mortality; secondary outcomes were primary fascia closure rate, length of treatment, complication rate, entero-atmospheric fistula rate and length of ICU stay. Results: A total of 591 patients were enrolled from 57 centers, and obese patients were 127 (21.5%). There was no difference in mortality between the two groups; complications developed during the open treatment were higher in obese patients (63.8% vs. 53.4%, p = 0.038) while post-closure complications rate was similar. Obese patients had a significantly longer duration of the open treatment (9.1 ± 11.5 days vs. 6.3 ± 7.5 days; p = 0,002) and lower primary fascia closure rate (75.5% vs. 89.5%; p < 0,001). No differences in fistula rate were found. There was a linear correlation between the duration of open abdomen and the BMI (Pearson’s linear correlation coefficient = 0,201; p < 0,001). Conclusions: Open abdomen in obese patients seems to be safe as in non-obese patients with similar mortality; however, in obese patients the length of open abdomen is significantly higher with higher complication rate, longer ICU length of stay and lower primary fascia closure rate. Trial registration number: ClinicalTrials.gov, Identifier: NCT02382770.

Atopic dermatitis (AD) is the most common chronic skin disease in children, with an increasing prevalence in the past three decades. Adequate treatment is prescribed for individual patient based on symptoms and disease severity. However, further underlying diagnosis should be researched when therapeutic strategies for symptoms fail and skin lesions and pruritus persist. We reported herein the case of a 19-month-old infant with a history of AD unresponsive to treatment due to the type 2 progressive familial intrahepatic cholestasis (PFIC). A new homozygous mutation of the ABCB11 gene was found. The severe pruritus, the early onset jaundice, poor growth and raised transaminase levels with normal gamma glutamyl transpeptidase have led to the suspicion of PFIC. The presence of severe AD and intrahepatic chronic cholestasis, both pruritus associated, could delay a proper diagnosis. To our knowledge, for the first time, a case of comorbidity between type 2 PFIC and AD-like disease had been described.

Purpose Several studies have demonstrated the oncologic equivalence of laparoscopic (LS) and open (OS) rectal cancer surgeries and have shown how challenging LS may become. Robotic surgery (RS) has emerged as a practical alternative, offering interesting advantages in comparison to both LS and OS. The aim of this study is to resolve the clinicopathologic outcome advantages of RS with respect to OS and LS techniques. Methods Patients with rectal cancer undergoing OS, RS, or LS were evaluated within the period from April 2009 to August 2011. The evaluations were carried out in 4 Italian hospitals. Perioperative clinicopathologic data, postoperative complications, and 3-year overall and disease-free survival (DFS) rates were analyzed. Results A total of 160 patients (94 male, 66 female) were included. A total of 105 patients underwent mini-invasive procedure (40 LS; 65 RS), whereas OS was performed in 55 patients. Anterior resection of rectal cancer was the most performed surgical procedure (139; 87%). Median operation time was significantly longer in the RS group (pConclusions Although RS for rectal cancer requires more time to be performed than LS and OS techniques, the analysis shows comparatively the feasibility and safety of RS in terms of perioperative clinicopathologic and medium-term outcomes.

Background A relationship between IgA nephropathy (IgAN) and celiac disease (CD) has been reported. We show the pathogenetic link for the first time. Case presentation A 39-year-old man with cystic fibrosis (CF) and CF-related diabetes started to present gross hematuria, back pain and headache. At admission, laboratory analysis showed increase in serum creatinine of 1.5 mg/dl, together with hematuria and mild proteinuria (1 g/24 h). He underwent a renal biopsy to investigate the cause of hematuria and renal failure. Biopsy was consistent with IgAN. In view of patient reported dyspepsia, an upper gastrointestinal endoscopy with duodenal biopsies was undertaken and was normal. We looked for mucosal deposits of tTG-2 in the duodenum and the renal mesangium. tTG-2 deposits were found both in the duodenum and in renal biopsies, where they topographically replicated mesangial IgA deposits. After one year on a continued gluten containing diet, the patient developed a Marsh 2 type duodenal pathology. Conclusions Our findings suggest a connection between CD and IgAN in terms of an immune-mediated gluten-induced pathogenesis even in the absence of villous atrophy and serum celiac autoantibodies. Electronic supplementary material The online version of this article (10.1186/s12876-018-0792-0) contains supplementary material, which is available to authorized users.

Background C3 glomerulonephritis is a rare glomerulopathy characterized at renal biopsy by C3 deposition, alone or with scanty immunoglobulins, as well as by an electron-dense material in mesangium, subendothelial and subepithelial space. An abnormal systemic activation of the alternative pathway of the complement cascade is responsible for the development of the disease if triggered by several possible environmental conditions. We report the first case in literature of a patient affected by cystic fibrosis and C3GN. Case presentation Our case involves a young woman with cystic fibrosis, who had persistent microscopic hematuria, proteinuria and hypocomplementemia C3 for over three months. Renal biopsy confirmed the diagnosis of C3 glomerulopathy. Complement system dysregulation was tested and resulted in a strong terminal pathway activation proved by high levels of sC5b-9 complex, amounting to 1588 ng/ml (normal value

Anastomotic leakage (AL) is a serious complication in colorectal surgery leading to significant morbidity and mortality. Progressively lower anastomoses are associated with a greater leak rate. Adequate bowel perfusion has been stressed as one of the key elements for suture healing. Currently, there is no widespread method to assess and quantify the perfusion of gastrointestinal anastomoses intraoperatively, besides the subjective evaluation by the surgeon. The aim of this paper is to describe the basis of Indocyanine Green (ICG) fluorescence guided surgery applied to assessment of bowel perfusion and to highlight studies on the use of fluorescence angiography (FA) in laparoscopic rectal surgery. ICG fluorescence guided surgery has increasingly been used as a tool for intraoperative diagnostics to assess microperfusion and viability of tissues by means of a real-time FA; this technique has achieved the role of major contribution to intraoperative decision making during surgical procedures, especially in order to assess bowel perfusion before anastomosis creation in colorectal surgery. Several studies in literature already reported that ICG FA as a feasible technique to decrease AL rate in colorectal surgery; to date no randomized controlled trials have been completed but large series and prospective studies that focus on fluorescence perfusion assessment in rectal surgery have been published. Real time intraoperative ICG fluorescent angiography (FA) is a safe and feasible technique to guide the surgeon in intraoperative decision-making process. ICG FA seems to reduce AL rates following rectal surgery for cancer. However large well-designed RCTs are needed to provide evidence for its routine use.

We present a case of splenosis of the abdomen and pelvis complicated by torsion of a splenic implant in a young female patient clinically mimicking an acute bowel ischemia. Splenosis is a benign condition defined as heterotopic auto-transplantation of splenic tissue throughout different body areas. It may occur after rupture of the spleen, either traumatic or secondary to surgical procedures. Although the presence of heterotopic splenic tissue is often asymptomatic and an incidental finding, it may present with sudden abdominal pain and bleeding. CT and MRI play a critical role in the detection of splenosis-related complications, such as torsion of the vascular pedicle and infarction. Splenosis torsion is extremely rare and it is still a diagnostic dilemma; the complication of abdominal splenosis should be considered in the differential diagnosis in patients with previous splenectomy.

The aim of this report is to assess whether the research issues priorities are perceived differently according to the Stakeholders (SH)'s individual knowledge of research topics and degree of training in biomedical research. Four groups of SH were enrolled in this study: 1. Skilled SH, specifically trained in biomedicine; 2. Unskilled untrained SH who responded to a written questionnaire in 2015; 3. SH who were trained for one year in a course delivered by professionals; 4. Untrained SH who responded to an online questionnaire in 2017. The large ranking order variability observed among groups addresses the question that the choices are markedly influenced by the SH's backgrounds. Such results emphasize the need to consider the education level and the delivery of ad hoc training activities by professionals to broaden the base of SH who may be considered qualified to transfer the Patient Centered Outcome Research principles into practice.

Maecenas’ character has been handed down variously and sometimes contradictorily by ancient sources; modern critics have contributed even more to stress extravagant features of his personality and writings. This paper aims to highlight the most important ways of interpretation and to suggest new hints of research starting from a re-analysis of texts.

A wireless local area network (WLAN) was first implemented at the University of Colorado at Boulder (UCB) in April of 2017. Only four 5.8 GHz band transceivers were present at the time. Now, there are eight different radios in place with the purpose of evaluating their performance. A long distance link was recently installed, as well as a medium distance link utilizing different radios. This network serves as a testbed for future installations to be made in the developing world as a part of the IEEE Smart Village program. Each radio is accompanied by a self-sustaining solar micro-grid. This micro-grid uses Maximum Power Point Tracking (MPPT) charge controllers to ensure maximum longevity of the LiFePO4 cells that are present at each station. An Arduino and a Raspberry Pi help monitor the hardware and try to mitigate as many failures as possible without requiring human intervention. The stations are also equipped with multiple radios that are used to relay information to a central server. The testbed is currently running two LigoWave LigoDLB Propeller 5s, two LigoWave LigoDLB 5-90-17 PROs, two LigoWave LigoPTP 5–23 PROs, and two MikroTik mANT 30 PA paired with MikroTik BaseBox 5s. The central server is located on the Engineering Tower at CU Boulder, behaving as a central node that can collect data and monitor all parts of the network. This data includes the energy production of the renewable energy sources (RESs), the consumption of the energy storage systems (ESSs), and the consumption of the loads attached to these. The server is consistently analyzing this data and has the ability to raise alerts when a station behaves erroneously. Additionally, continuous ping and network throughput tests are run, in order to compare the behavior of different radios at different distances. The availability of this data allows for close analysis regarding the suitability of certain components and communication methods in remote areas of the world.

Genetic traceability has a key role in the product certification, but it is rarely implemented in sheep so far, especially in the fresh meat sector. In this study, the case of the Sambucana sheep is analysed with the aim of developing a genetic system able to certify the origin of its traditional product, the Sambucano lamb, protected by a registered trademark. A set of 14 microsatellite markers was identified as an efficient tool to genetically discriminate the Sambucana sheep from other breeds potentially involved in mislabelling and to allow for an effective allocation test of meat cuts labelled as ‘Guaranteed Sambucano lamb’. The paternity test proved to be an additional means to improve the reliability of the control. The traceability system here described is easy to implement in local minor sheep breeds and is recommended in the framework of meat certification.

Background We assessed how the diagnosis of Celiac Disease (CD) is made and how the new ESPGHAN guidelines can be applied in children from countries with different resources. Methods A real life prospective study was performed in 14 centres of 13 different Mediterranean countries. Participants were asked to apply the usual diagnostic work-up for CD according to their diagnostic facilities. Results There were 1974 patients enrolled in the study, mean age 4 years, 10 months; 865 male, 1109 female. CD was confirmed in 511 (25.9%) and was unconfirmed in 1391 (70.5%) patients; 14 patients were diagnosed as having CD according to the new ESPGHAN guidelines, 43 patients were classified as having potential CD. In all participating countries the diagnosis of CD relied on histology of duodenal biopsy; in 5 countries, HLA, and in one country endomysial antibodies (EMA) were not available. Symptoms did not add a significant increase to the pre-test probability of serological tests. The positive predictive value of tissue transglutaminase type 2 (tTG) antibodies performed with different kits but all corresponding to those recommended by ESPGHAN was 96.1% (95% CI 94–97.9%) in presence of tTG > 10xULN. In 135 patients with tTG >10xULN, HLA genotyping was performed and in all it was compatible with CD. Conclusions The results of our study show that CD diagnosis still relies on intestinal biopsy in the Mediterranean area. New ESPGHAN criteria are not applicable in 5 countries due to lack of resources needed to perform HLA genotyping and, in one country, EMA assay. Further simplification of the new ESPGHAN guidelines might be made according to what preliminarily the present results suggest if confirmed by new prospective studies.

Background Thalidomide is an effective therapy in children with inflammatory bowel disease refractory to standard treatments, but thalidomide-induced peripheral neuropathy (TiPN) limits its long-term use. We aimed to investigate the risk factors and the outcome of TiPN in children with inflammatory bowel disease. Methods Within a retrospective multicenter cohort study, we evaluated prevalence and evolution of TiPN. Clinical data and candidate genetic profiles of patients with and without TiPN were compared with detect predisposing factors. Results One hundred forty-two patients were identified. TiPN was found in 72.5% of patients (38.7% clinical and instrumental alterations, 26.8% exclusive electrophysiological anomalies, and 7.0% exclusive neurological symptoms). Median TiPN-free period of treatment was 16.5 months; percentage of TiPN-free patients was 70.0% and 35.6% at 12 and 24 months of treatment, respectively. The risk of TiPN increased depending on the mean daily dose (50-99 mg/d adjusted hazard ratio 2.62; 95% confidence interval [CI], 1.31-5.21; 100-149 mg/d adjusted hazard ratio 6.16; 95% CI, 20.9-13.06; >150 mg/d adjusted hazard ratio 9.57; 95% CI, 2.6-35.2). Single nucleotide polymorphisms in ICAM1 (rs1799969) and SERPINB2 (rs6103) genes were found to be protective against TiPN (odds ratio 0.15; 95% CI, 0.03-0.82 and 0.36; 95% CI, 0.14-0.88, respectively). TiPN was the cause of drug suspension in 41.8% of patients. Clinical symptoms resolved in 89.2% of cases, whereas instrumental alteration persisted in more than half of the patients during a short follow-up. Conclusions In children with inflammatory bowel disease, TiPN is common but mild and generally reversible. Cumulative dose seems to be the most relevant risk factor, whereas polymorphisms in genes involved in neuronal inflammation may be protective.

Background: No definitive data about open abdomen (OA) epidemiology and outcomes exist. The World Society of Emergency Surgery (WSES) and the Panamerican Trauma Society (PTS) promoted the International Register of Open Abdomen (IROA). Methods: A prospective observational cohort study including patients with an OA treatment. Data were recorded on a web platform (Clinical Registers (R)) through a dedicated website: www.clinicalregisters.org. Results: Four hundred two patients enrolled. Adult patients: 369 patients; Mean age: 57.39 +/- 18.37; 56% male; Mean BMI: 36 +/- 5.6. OA indication: Peritonitis (48.7%), Trauma (20.5%), Vascular Emergencies/Hemorrhage (9.4%), Ischemia (9.1%), Pancreatitis (4.2%), Post-operative abdominal-compartment-syndrome (3.9%), Others (4.2%). The most adopted Temporary-abdominal-closure systems were the commercial negative pressure ones (44.2%). During OA 38% of patients had complications; among them 10.5% had fistula. Definitive closure: 82.8%; Mortality during treatment: 17.2%. Mean duration of OA: 5.39(+/- 4.83) days; Mean number of dressing changes: 0.88(+/- 0.88). After-closure complications: (49.5%) and Mortality: (9%). No significant associations among TACT, indications, mortality, complications and fistula. A linear correlationexists between days of OA and complications (Pearson linear correlation = 0.326 p

BACKGROUND Diaphragmatic rupture (DR) is a rare and potentially life-threatening event caused by trauma or spontaneously. DR occasionally occurs several months after the injury. Chest X-ray and computed tomography are the most effective diagnostic methods. Delay in DR diagnosis occurs frequently. This study aimed to examine and improve our understanding of the etiology, clinical presentation, and management of DR. METHODS This study was performed at the Emergency and General Surgery Department of Fondazione I.R.R.C.S. Ca Granda, Ospedale Policlinico in Milan (Italy). Patients diagnosed with DR between 2001 and 2011 who underwent surgery were included, and their data were retrospectively collected. RESULTS Fourteen patients were diagnosed with DR, mainly left-sided DR. Road traffic collisions were the main causes (86%). DR diagnosis was preoperatively established in eight patients (57%). Chest X-ray was diagnostic in 50% of the patients and computed tomography in three patients (60%). Twelve patients had a diaphragmatic hernia. DR was repaired with a mesh in two patients. Mean hospital stay was 16.6 days. CONCLUSION Difficulty in achieving early diagnosis of DR is due to its nonspecific presentation. High index of suspicion is needed. Its treatment is using surgery involving reduction of the viscera and repair of the diaphragm defect.

Dear Editor: Perianal manifestations are quite frequent in Crohn’s disease (CD): simple or complex fistulas, skin tags, haemorrhoids, ulcers, fissures and anal strictures may develop in association with active colorectal inflammation [1, 2]. Symptoms of perianal Crohn’s disease (PCD) vary in terms of severity but are usually recurrent and persistent; combined surgical and medical approach is the gold standard for therapy [1, 2]. Conversely, fistula-associated malignancies are very rare, but few cases among CD patients have been reported in literature; advanced stage at diagnosis and poor outcome are common features [3]. Detection of anorectal carcinoma arising on chronic complex PCD may be challenging, and delayed diagnosis could impair chances of radical treatment. Out of 344 CD-related operations conducted between January 2007 and June 2014 at a single tertiary referral institution, 83 procedures were performed for perianal disease on 60 patients. Four patients were found to have anorectal carcinoma associated with perianal fistula; clinical characteristics, diagnostic and treatment modalities for these patients are presented and discussed. Case 1 A 31-year-old female with a 13-year history of perianal CD and terminal ileitis underwent examination under anaesthesia (EUA) for transsphincteric fistula refractory to treatment. Multiple biopsies demonstrated mucinous anal adenocarcinoma. Abdominoperineal resection extended to the posterior vaginal wall, and coccyx, inguinal linfectomy and ileocecal resection were performed (p T4b N0). She received postoperative chemotherapy and steroids for recurrence of ileal CD. Four years after resection, a pelvic recurrence was detected and chemoradiotherapy started; the patient however died at 53 months from surgery due to disseminate disease. Case 2 A 45-year-old female was admitted for persistent rectovaginal fistula and active colitis. She was diagnosed with perianal CD 23 years before and had previous resection of terminal ileum and right colon. Sphincter-sparing proctocolectomy was performed. On histology, colloid adenocarcinoma of the anus associated with fistula was demonstrated (pT3 N0); she received chemoradiotherapy postoperatively. After 20 months, she developed a pelvic recurrence on the vaginal wall and underwent surgical excision; no signs of further recurrences were seen at 32month follow-up. Case 3 A 44-year-old male was diagnosed with perianal and ileocoecal CD at 21 and underwent ileocecal resection at that time. He was referred to our institution for recurrent abscesses and refractory perianal fistulas; although there was high suspicion for tumour degeneration on first clinical examination, office biopsies failed to demonstrate malignancy. EUAwith deeper biopsies showed mucinous adenocarcinoma of the Electronic supplementary material The online version of this article (doi:10.1007/s00384-015-2140-y) contains supplementary material, which is available to authorized users. A. Zefelippo (*) : S. Costa : E. Contessini-Avesani General and Emergency Surgery Unit, Ospedale Maggiore Policlinico, via F. Sforza 28, 20122 Milan, Italy e-mail: arianna.zefelippo@policlinico.mi.it

PURPOSE: This study aims to evaluate the role of (11)C-choline PET/CT in patients with biochemical relapse after radical prostatectomy (RP) showing prostate-specific antigen (PSA) values lower than 0.5 ng/mL. METHODS: We performed (11)C-choline PET/CT in 71 consecutive patients previously treated with RP showing PSA values lower than 0.5 ng/mL. (11)C-Choline PET/CT was performed following standard procedure. (11)C-Choline PET/CT-positive findings were validated by transrectal ultrasonography + biopsy, repeated (11)C-choline PET/CT, other conventional imaging modality, and histology. RESULTS: (11)C-Choline PET/CT was true positive in 15/71 (21.1%). (11)C-Choline uptake was observed in pelvic lymph nodes (7/71; 9.9%), in the prostatic bed (7/71; 9.9%), and in bone (1/71; 1.4%). Mean PSA, PSA doubling time (PSAdt), and PSA velocity (PSAvel) values ± SD in (11)C-choline PET/CT-positive patients was 0.37 ± 0.1 ng/mL, 3.4 ± 2.1 months, and 0.05 ± 0.1 ng/mL/yr, respectively. (11)C-Choline PET/CT was false negative in 2 patients and false positive in 1 patient. Among all variables, only PSAdt and the ongoing hormonal treatment were statistically significant in the prediction of a positive (11)C-choline PET/CT at multivariate analysis. CONCLUSIONS: (11)C-Choline PET/CT could be used early after biochemical failure even if PSA values are very low, preferentially in hormonal resistant patients showing fast PSA kinetics. An early detection of the site of relapse could lead to a personalized and tailored treatment.

Some studies have shown a direct relationship between nutritional status and survival in Cystic Fibrosis (CF) patients. Body wasting, defined as a percentage of the ideal body weight for age, has been shown to be an independent predictor of mortality in CF. With respect to height only two studies were performed and these studies suggested that stunting is an important determinant of survival but both did not adjust statistical analysis for confounding variables. We aimed at determining the association between stunting and risk of mortality in CF patients.393 CF patients older than 6 years of age, 95 deceased, as cases, and 298 live, as controls, were enrolled in a nested case-control study. Stunting was defined by a height percentile5th. We performed a multivariate statistical analysis including height percentile and the following possible confounding variables: age, gender, Body Mass Index (BMI), Forced Expiratory Volume in 1 s (FEV1), genotype, pancreatic status, CF-related diabetes, colonization with Pseudomonas aeruginosa and/or Burkholderia cepacia.In the adjusted analyses stunting (OR 2.22 [IC 95%1.10-4.46]), wasting (OR 5.27 [IC 95% 2.66-10.41]), and FEV1 40% of predicted (OR 10.60 [IC 95% 5.43-20.67]) resulted the covariates that significantly predict the risk of mortality.Our study shows, for the first time, that stunting is a significant and independent risk factor for mortality in CF patients, and warrants an intervention of nutritional rehabilitation. Considering that nutritional interventions in stunted patients should be prolonged, are invasive and expensive, and might affect self-esteem and body image, their efficacy should be fully assessed by Randomised Controlled Trials.

Background/Aims: We evaluated the diagnostic variability and reproducibility of endoscopic signs in two populations with a different pretest likelihood of celiac disease (CD). Methods: We recruited 289 CD patients (both adults and children) in a multicenter prospective study. Group 1 (high risk) included 111 patients referred for positive serology. Group 2 (low risk) included 178 unselected patients. Mosaic pattern, reduction/loss of Kerckring's folds, scalloping of the valvulae conniventes and a nodular pattern were the endoscopic findings looked for in the duodenum. Results: In group 1, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of endoscopic findings were 100, 84.6, 94.2 and 100% in adults, and 86.8, 9.1, 82.1 and 12.5% in children. In group 2, the sensitivity, specificity, PPV and NPV of endoscopic findings were 33.3, 91.4, 7.7 and 98.5% in adults, and noncalculable, 78.3, 0.0 and 100% in children. Comparing group 1 and group 2, there was a statistically significant difference in sensitivity and PPV in adults, and in specificity, PPV and NPV in children. Concerning the reproducibility of endoscopic findings, a wide variability of κ values was found. Conclusion: Endoscopic signs have low reproducibility for CD, and their diagnostic value in selecting patients for multiple intestinal biopsies is unacceptable, especially in populations with low disease prevalence.

Background: Eosinophilic esophagitis (EoE) has been defined as "asthma of the esophagus" for the large number of similarities between the two diseases. Omalizumab is an anti-Immunoglobulin E (IgE) antibody currently approved only in allergic IgE-mediated severe persistent uncontrolled asthma and in chronic spontaneous urticaria unresponsive to antihistamines, but it has been tried in other diseases, too. Case presentation: We present herein the case of a 13-year-old boy, affected from preschool age by severe chronic allergic asthma poorly controlled despite a generous long-term therapy, and, since he was 8 years old, by eosinophilic esophagitis, responsive to courses of strict elimination diet and semi-elemental diet, even if very burdensome for his quality of life. At the age of 11.5 years, for inadequate asthma control, he started to receive therapy with omalizumab. After the first month and for the entire duration (18 months) of omalizumab treatment, asthma was well controlled, long-term conventional therapy was gradually withdrawn and lung- function improved. Concerning EoE, after an initial clinical but not histological remission during the first few months of treatment with omalizumab, the patient experienced an exacerbation of gastrointestinal symptoms. Therefore, he started treatment with topical steroids which was effective to improve gastrointestinal symptoms. However, EoE is still steroid-dependent. Currently, he continues both treatments: omalizumab for asthma and topical steroid for EoE. Conclusions: This case report confirms that omalizumab is an effective treatment in patients with severe persistent, uncontrolled asthma. On the other hand, in our patient it did not produce persistent improvement neither on symptoms nor on biopsy findings of EoE. The outcome of this case might indicate different pathogenic mechanism(s) of the two diseases.

Background Chemotherapy‐induced nausea and vomiting (CINV) is a distressing side effect that can negatively impact patients' quality of life and could discourage completion of chemotherapy, thereby affecting overall treatment outcomes. Although adherence to antiemetic guidelines can reduce CINV incidence in patients receiving highly or moderately emetogenic chemotherapy, CINV control remains inadequate. Aims The objectives of this survey were to determine oncologists' practice patterns in CINV management, identify factors that contribute to antiemetic treatment failure, and determine the outcomes of uncontrolled CINV on health care resource utilisation and on patients' attitude towards chemotherapy. Methods and results Quantitative market research was performed using an online questionnaire. Responses from 300 European oncologists who prescribe antiemetics and see ≥50 patients/month were analysed. Results showed that the main reasons reported by oncologists for antiemetic treatment failure were underestimating the emetogenic potential of chemotherapy, utilising weaker antiemetic regimens than required, and patient non‐adherence because of administration mistakes or missed/delayed doses. Educational initiatives for the oncology multidisciplinary team may help improve guideline‐consistent prescribing. Also, the availability of simpler, more convenient antiemetic therapies may improve guideline adherence and patient compliance during home administration. Conclusion Achieving effective CINV control is a crucial goal to improve patients' quality of life, which should optimise chemotherapy outcomes, and would ultimately reduce health care costs.

AIM: The aim of this study was to compare C-choline PET/CT, prostate-specific antigen (PSA), PSA kinetics, and C-choline uptake in recurrent metastatic prostate cancer patients with osteoblastic and osteolytic bone metastases. PATIENTS AND METHODS: We retrospectively analyzed 140 patients with the following criteria: (a) positive bone lesions identified with C-choline PET/CT and validated as true positive by histology (14.2%), correlative imaging (33.4%), or clinical follow-up (52.4%); (b) after radical prostatectomy (67.9%) or primary radiotherapy (22.1%); (c) proven biochemical relapse with rising PSA levels; (d) no chemotherapy, zoledronic acid, or palliative bone external beam radiation therapy previously administrated during biochemical relapse; and (f) asymptomatic for bone pain. Lesions were categorized as osteoblastic, osteolytic, or bone marrow lesions. Patients were divided into osteoblastic and osteolytic patient groups. RESULTS: C-Choline PET/CT detected oligometastatic bone disease (1-3 lesions) in 98 (70%) of the 140 patients and multiple bone lesions in 42 (30%) of the 140 patients. By per-lesion analysis of 304 lesions, there were 184 osteoblastic, 99 osteolytic, and 21 bone marrow lesions.By per-patient analysis, 97 (69.3%) of the 140 patients were in the osteoblastic group, whereas 43 (30.7%) of the 140 patients were in the osteolytic group. Statistically significant differences in SUVmax (P < 0.001), fast PSA doubling time (P = 0.01), and PSA velocity (P = 0.01) were observed between osteoblastic (lower values) and osteolytic (higher values) groups. By multivariate analysis, fast PSA doubling time was a significant predictor for osteolytic lesions. CONCLUSIONS: We demonstrated differences in PSA kinetics and SUVmax between osteolytic and osteoblastic lesions. C-Choline PET/CT may identify patients that could benefit from early targeted therapies, depending on the type of bone lesions expressed.

AIM: The aim of this study was to evaluate of C-choline PET/CT in bladder cancer (BC) patients with suspected relapse after primary therapy. METHODS: Twenty-five BC patients with surgery (21 [84%]) or radiotherapy (4 [16%]) with curative intent had PET/CT for suspicion of relapse. Mean TNM was T2b N0 M0 (range, T1a N0 M0 to T4 N2 M0), whereas mean age was 71.3 years (range, 50-85 years). Nine (36%) of 25 were treated with adjuvant or salvage chemotherapy within 6 months before PET/CT. Positive findings were validated by histology or correlative imaging and/or clinical follow-up lasting at least 12 months. Age, TNM, histology, previous chemotherapy, and type of primary treatment were correlated with PET/CT positivity by univariate and multivariate binary logistic regression analysis. RESULTS: C-choline PET/CT was positive in 16 (64%) of 25. Six (37.5%) of 16 were positive in residual bladder/bladder bed, with 2 local false positive (FP) and 1 false negative (FN) on lymph nodes (LNs); 3 of 16 patients had PET-positive LNs with 1 FP; 1 of 16 patients showed distant metastases. Two (12.5%) of 16 had positive residual bladder/bladder bed and locoregional LNs; 1 (6.3%) of 16, residual bladder/bladder bed and bone; metastasis, 1 (6.3%) of 16 residual bladder/bladder bed and lung metastasis; 2 (12.5%) of 16, LN and distant metastasis. Five (56%) of 9 of PET negatives were FN in residual bladder/bladder bed. Eighteen (72%) of 25 were validated by histology, with 7 (18%) of 25 by correlative imaging and/or clinical follow-up. C-choline PET/CT was sensitive, specific, and accurate, with good positive and negative predictive values for local relapse of 66.7%, 84.6%, 76%, 80%, and 73.3% and 90%, 93.3%, 92%, 90%, and 93.3% for LNs and distant relapse, respectively. No FP or FN was detected for distant metastasis. None of the investigated factors were statistically significant. CONCLUSION: C-choline PET/CT is useful for restaging BC suspected of relapse, especially for the evaluation of LN or distant metastases.

Summary Background: It is controversial whether CARD15 variants are truly associated with a more severe form of Crohn's disease. The relative role of CARD15 genotype and smoking in Crohn's disease progression is also debated. Aim: To investigate the association between CARD15 variants and history of resective surgery in patients with Crohn's ileal disease, taking into account smoking as a possible confounding factor. Methods: We originally assessed CARD15 genotype in 239 north Italian Crohn's disease patients (mean follow-up: 10.1 ± 8.1 years). We then focused on 193 patients with proven ileal involvement, 70 of whom (36.3%) carried CARD15-mutated alleles (G908R, R702W, L1007fs). Results: Carriage of CARD15 variants was positively associated with family history and ileal-only disease and negatively associated with uncomplicated behaviour at maximal follow-up (P

BACKGROUND: We aimed at assessing the factors that can influence results of the dissemination of an already validated, new generation commercial Point-of-Care Test (POCT) for detecting celiac disease (CD), in the Mediterranean area, when used in settings where it was designed to be administered, especially in countries with poor resources. METHODS: Pragmatic study design. Family pediatricians at their offices in Italy, nurses and pediatricians in Slovenia and Turkey at pediatricians', schools and university primary care centers looked for CD in 3,559 (1-14 yrs), 1,480 (14-23 yrs) and 771 (1-18 yrs) asymptomatic subjects, respectively. A new generation POCT detecting IgA-tissue antitransglutaminase antibodies and IgA deficiency in a finger-tip blood drop was used. Subjects who tested positive and those suspected of having CD were referred to a Celiac Centre to undergo further investigations in order to confirm CD diagnosis. POCT Positive Predictive Value (PPV) at tertiary care (with Negative Predictive Value) and in primary care settings, and POCT and CD rates per thousand in primary care were estimated. RESULTS: At tertiary care setting, PPV of the POCT and 95% CI were 89.5 (81.3-94.3) and 90 (56-98.5) with Negative Predictive Value 98.5 (94.2-99.6) and 98.7% (92-99.8) in children and adults, respectively. In primary care settings of different countries where POCT was performed by a different number of personnel, PPV ranged from 16 to 33% and the CD and POCT rates per thousand ranged from 4.77 to 1.3 and from 31.18 to 2.59, respectively. CONCLUSIONS: Interpretation of POCT results by different personnel may influence the performance of POC but dissemination of POCT is an urgent priority to be implemented among people of countries with limited resources, such as rural populations and school children.

Patients involved on coeliac disease (CD) have atypical symptoms and often remain undiagnosed. Specific oral manifestations are effective risk indicators of CD and for this reason an early diagnosis with a consequent better prognosis can be performed by the dentist. There are not researches analysing the frequency of these oral manifestations in potential coeliac patients. The aim of this study is to investigate the oral hard and soft tissue lesions in potential and ascertained coeliac children in comparison with healthy controls. 50 ascertained children, 21 potential coeliac patients, and 54 controls were recruited and the oral examination was performed. The overall oral lesions were more frequently present in CD patients than in controls. The prevalence of oral soft tissue lesions was 62% in ascertained coeliac, 76.2% in potential coeliac patients, and 12.96% in controls (P<0.05). Clinical dental delayed eruption was observed in 38% of the ascertained coeliac and 42.5% of the potential coeliac versus 11.11% of the controls (P<0.05). The prevalence of specific enamel defects (SED) was 48% in ascertained coeliac and 19% in potential coeliac versus 0% in controls (P<0.05;OR=3.923). The SED seem to be genetically related to the histological damage and villous atrophy.

e18158Background: Antiemetic guidelines recommend the combination of a neurokinin-1 receptor antagonist (NK1 RA), a 5-hydroxytryptamine-3 receptor antagonist (5HT3 RA), and dexamethasone for prophy...

Recently introduced in the treatment algorithms and guidelines for the treatment of ulcerative colitis, biological therapy is an effective treatment option for patients with an acute severe flare not responsive to conventional treatments and for patients with steroid dependent disease. The reduction in hospitalization and surgical intervention for patients affected by ulcerative colitis after the introduction of biologic treatment remains to be proven. Furthermore, these agents seem to be associated with increase in cost of treatment and risk for serious postoperative complications. Restorative proctocolectomy with ileal pouch-anal anastomosis is the surgical treatment of choice in ulcerative colitis patients. Surgery is traditionally recommended as salvage therapy when medical management fails, and, despite advances in medical therapy, colectomy rates remain unchanged between 20% and 30%. To overcome the reported increase in postoperative complications in patients on biologic therapies, several surgical strategies have been developed to maintain long-term pouch failure rate around 10%, as previously reported. Surgical staging along with the development of minimally invasive surgery are among the most promising advances in this field.

Background In the absence of consolidated pipelines to archive biological data electronically, information dispersed in the literature must be captured by manual annotation. Unfortunately, manual annotation is time consuming and the coverage of published interaction data is therefore far from complete. The use of text-mining tools to identify relevant publications and to assist in the initial information extraction could help to improve the efficiency of the curation process and, as a consequence, the database coverage of data available in the literature. The 2006 BioCreative competition was aimed at evaluating text-mining procedures in comparison with manual annotation of protein-protein interactions. Results To aid the BioCreative protein-protein interaction task, IntAct and MINT (Molecular INTeraction) provided both the training and the test datasets. Data from both databases are comparable because they were curated according to the same standards. During the manual curation process, the major cause of data loss in mining the articles for information was ambiguity in the mapping of the gene names to stable UniProtKB database identifiers. It was also observed that most of the information about interactions was contained only within the full-text of the publication; hence, text mining of protein-protein interaction data will require the analysis of the full-text of the articles and cannot be restricted to the abstract. Conclusion The development of text-mining tools to extract protein-protein interaction information may increase the literature coverage achieved by manual curation. To support the text-mining community, databases will highlight those sentences within the articles that describe the interactions. These will supply data-miners with a high quality dataset for algorithm development. Furthermore, the dictionary of terms created by the BioCreative competitors could enrich the synonym list of the PSI-MI (Proteomics Standards Initiative-Molecular Interactions) controlled vocabulary, which is used by both databases to annotate their data content.

Cystic fibrosis (CF) is the most common autosomal-recessive condition affecting the white population, with an incidence ranging between 1:2500 and 1:1800 births. It is caused by a mutation in the CFTR gene, encoding the polyprotein CF transmembrane conductance regulator (CFTR), which functions as an ATP-responsive chloride channel in the apical membrane of epithelial cells. Pathologic changes related to CFTR mutations mostly affect secretory cells, resulting in low secretion volume and increased viscosity and promoting mucosal obstruction in the lung, pancreas, biliary tract, sinuses and reproductive tract [1]. Patients with CF currently show a continuing improvement in their life expectancy, an improvement that allows for better multidisciplinary monitoring and earlier therapeutic interventions. Owing to their longer life expectancy, CF patients present complications that were not recorded before [2]. This is illustrated by the following report of two cases of renal AA amyloidosis in women with CF.