Consensus paper on postural dysfunction: recommendations for prevention, diagnosis and therapy.

Good fundamentals of posture and balance are essential for the efficient performance of both simple daily tasks and more complex movement patterns. In particular, postural balance is the ability to keep the body in equilibrium and to regain balance after the shift of body segments: postural control mechanisms of integration of the visual, vestibular and foot afferential channels contribute to this. This document provides recommendations based on scientific evidence, clinical practice, and consensus between experts concerning the prevention, diagnosis, and treatment of postural dysfunction at the three stages of life as the developmental age, adult age, and old age > 65 years and follows the "National Guidelines on Classification and Measuring of Posture and its Dysfunctions" per the Italian Ministry of Health (December 2017). The paper answers four main questions: i) "Which measures can be adopted to prevent postural dysfunctions?" ii) "What can we do in order to make a correct diagnosis of postural dysfunction?" iii) "What are the correct treatment programs for postural dysfunctions?" iv) Which professional competencies and experiences are useful for preventing, diagnosing and treating postural dysfunctions? By the Consensus of the Experts and the scientific evidence, emerge that the approach to postural dysfunctions requires a multidisciplinary and interdisciplinary team. Furthermore, rehabilitation treatment interventions must be specific to the age groups that have been indicated, to consider the integration of the main systems and subsystems of postural control that change with age.

Prospective study of the effects of concomitant medications on thiopurine metabolism in inflammatory bowel disease.

BACKGROUND: Thiopurines are increasingly used in the treatment of inflammatory bowel disease (IBD), being the most common immunosuppressive therapy; however, potentially harmful interactions between thiopurines and other drugs (especially 5-aminosalicylic acid, 5-ASA) were described. AIM: To explore potential interactions between thiopurines and concomitant medications. METHODS: A total of 183 consecutive IBD patients were enrolled. Clinical characteristics and concomitant medications were recorded. Thiopurine metabolism was analysed with thiopurine S-methyl transferase (TPMT) genetic variants and enzyme activity assays. Comparisons were carried out with stratification of patients according to clinical characteristics and active treatments. RESULTS: Based on TPMT genetics, 95% IBD patients were wild-type homozygous, the remaining being heterozygous. Median TPMT activity was 24.9 U/Hgb g (IQR 20.7-29.5). No difference in TPMT activity was noted according to 5-ASA exposure. IBD patients on thiopurines had higher TPMT activity levels, but no dose-effect was evident. No difference in TPMT activity was observed in 41 (63%) patients co-treated with 5-ASA. In patients on active thiopurines also, 6-TGN and 6-MMP levels were evaluated and no significant difference was observed based on co-medication. TPMT activity was independently associated only with thiopurines dose (P = 0.016). CONCLUSIONS: Our data suggest the absence of significant interactions between thiopurines and 5-ASA.

Epidural plus general anesthesia vs general anesthesia alone for elective aortic surgery: effects on gastric electrical activity and serum gastrin secretion.

BACKGROUND: The aim of this study was to evaluate differences in electrogastrographic activity and serum gastrin secretion in patients subjected to general anesthesia (GA) vs blended anesthesia (BA = GA plus epidural analgesia) for abdominal aortic surgery. METHODS: Thirty-four patients (all males: 28 with abdominal aorta aneurysm, 6 with obstructive aorto-iliac disease; mean age: 68+/-7 years) were randomly assigned either to GA (N.=17) or to BA (N.=17) for abdominal aortic surgery. Each patient was evaluated for serum gastrin secretion at the time of electrogastrography (EGG) 24 h before and after surgery, using ambulatory equipment. Gastrin levels were tested under fasting conditions and after a standard meal. EGG shows gastric electrical activity that parallels gastric motor activity. RESULTS: Before surgery, no significant difference was found for any of the EGG parameters or the serum gastrin integrated value (area under the curve [AUC]) between the two groups of patients. After surgery, an increased frequency of electrical waves (tachygastria) was observed in 22% of those undergoing GA and in 5% of patients undergoing BA. The power ratio (postprandial/fasting total power) was exceedingly high (>4) in 53% of the GA patients and in 11% of the BA patients (P<0.05). The gastrin AUC was 263+/-58 pg/mL in the GA group and 179+/-92 pg/mL in the BA group (P<0.01). CONCLUSIONS: An excess of EGG activity and serum gastrin secretion was observed in patients undergoing GA vs those submitted to BA. Thus, the latter procedure seems to affect gastric function less than GA alone.

US evaluation of patients affected by IBD: how to do it, methods and findings.

Intestinal US has to be performed very accurately, to obtain an exploration of both small bowel and cholical loops that will be the most complete that is possible; so, this technique requires adequately trained operators. Convex and linear probes with frequency between 3.5 and 7.5 MHz are used: the first ones for the panoramic evaluation and to study the middle-distal sigma and rectum; the second ones to perform a detailed examination of the bowel wall. US allows to evaluate not only the thickness and structure of the bowel wall, but also the content and peristalsis of the loops, their compressibility and movability, the perivisceral spaces and the abdominal organs. In Crohn's disease, US, completed everytime by the color-power-Doppler, shows wall thickening until 20 mm and above, with multi-stratified structure that could be regular, or more and more altered until the hypoechogenic view; the bowel vascularisation could be absent or less or more increased, due to the stadium of the disease itself. Furthermore, US allows to demonstrate the presence of stenosis and various other complications (abscesses inside or outside the walls, fistulas, involvement of other organs, free fluid collections); the use of II generation US contrast media could afford information about the activity of the disease. US has a very important role in the follow-up of patients with diagnosis of Crohn's disease, to monitor the response to the medical therapy and to discover complications; US must be performed as first in subjects with abdominal pain and diarrhea, to select the ones that need more invasive examinations.

The role of endoscopic assessment in ulcerative colitis in the era of infliximab.

Endoscopic evaluation of mucosal appearance is important for the clinical management of ulcerative colitis patients, as it offers valuable prognostic tools and data useful to change the management and treatment strategies. In the field of severe ulcerative colitis, partial endoscopy and bioptic sampling allows to obtain additional and relevant prognostic information: if severe endoscopic lesions are present, response to standard treatment is less likely, and if CMV superinfection is detected, anti-viral treatment should be added to conventional treatments. When clinical remission is obtained with conventional treatments, distal colonoscopy may add valuable data: the occurrence of complete endoscopic healing is a major predictor of long-term remission with no clinical activity. Finally, biologic treatments, and mainly infliximab, were shown to induce remarkable and significant mucosal healing also in ulcerative colitis, and patients with complete endoscopic healing in response to infliximab were shown to be more likely to experience fewer clinical relapses during the follow-up. Therefore endoscopic evaluation has to be considered a major prognostic marker in ulcerative colitis. In this review data from the Literature supporting this role will be reviewed.

Reproducibility of bowel ultrasonography in the evaluation of Crohn's disease.

BACKGROUND: Bowel ultrasonography is increasingly used in the detection and follow-up of patients with Crohn's disease, but a limitation to its further diffusion is the lack of standardisation of ultrasonography parameters. AIMS: This study aimed to standardise the most common bowel ultrasonography parameters in order to develop an unequivocal imaging interpretation and to assess bowel ultrasonography reproducibility. PATIENTS: Twenty patients with Crohn's disease were examined. METHODS: Six ultrasonographers (mean bowel ultrasonography experience=16 years) performed the study. They chose and discussed a common assessment methodology concerning eight ultrasonography parameters: bowel wall thickness, bowel wall pattern, bowel wall blood flow, enlarged mesenteric lymph nodes, mesenteric hypertrophy, abdominal free fluid, and stenosis or fistulae at four preliminary meetings. The day of the study operators were randomised to two rooms where they independently and in turn performed ultrasonography scans. Interobserver agreement was scored by kappa statistics. RESULTS: Excellent k values were observed for bowel wall thickness (0.72-1). k Values were poor for bowel wall pattern (-0.22-0.85) and good for bowel wall blood flow (0.53-0.89). The presence of lymph nodes was reproducible (0.56-0.90) except in one case (0.25). Concordance on free fluid was excellent (0.85-1), whereas that on mesenteric hypertrophy was generally poor (0.14-0.69). Agreement was excellent for stenosis (0.81-1) whereas that for fistula was fair in room abscesses (0.31-0.48) and very good in room B (0.87-1). CONCLUSION: Bowel ultrasonography signs used in Crohn's disease can be standardised as most of them showed a fair to good reproducibility. In particular, bowel wall thickness, the most relevant parameter for Crohn's disease detection, showed an excellent reproducibility.

Acute diarrhea during azathioprine treatment of type I autoimmune hepatitis.

Sporadic descriptions of acute onset of watery diarrhea within a few hours to a few weeks azathioprine administration beginning have been reported, particularly in inflammatory bowel disease patients. This article reports the case of a woman treated with azathioprine because of type I autoimmune hepatitis, who developed acute watery diarrhea after more than two months of therapy. In two occasions the patient reassumed the drug and in a few hours diarrhea recurred. Subsequent 6-mercaptopurine treatment was well tolerated, suggesting that the previous side-effect could be due to the nitroimidazole moiety of azathioprine.

Endoscopic ultrasound-fine needle aspiration (EUS-FNA) for pancreatic lesions: effectiveness in clinical practice.

BACKGROUND: Diagnosis of pancreatic masses is often difficult. Endoscopic ultrasound-fine needle aspiration has been proposed as the best single-step strategy. AIMS: To prospectively evaluate feasibility, effectiveness and safety of endoscopic ultrasound-fine needle aspiration of pancreatic masses in a consecutive study of unselected patients. METHODS: Two hundred ninety-three patients were enrolled in two referral Hospitals in Northern Italy. All patients were referred either due to the presence of imaging test abnormalities (suspected or evident masses, or features indirectly suggesting the presence of a mass) or due to clinical or biochemical findings suggesting pancreatic cancer in the absence of positive imaging. All patients underwent linear array endoscopic ultrasound and, when indicated, fine needle aspiration. All procedures were recorded prospectively. The final diagnosis was established at the end of follow-up or when the patients underwent surgery or died. RESULTS: Fine needle aspiration was indicated in 246 of 293 cases (84%), considered technically feasible in 232 of 246 cases (94%) and gave adequate samples for histopathological diagnosis in 204 of 232 cases (88%). Endoscopic ultrasound sensitivity, specificity and accuracy were 79, 60 and 72%, respectively; the corresponding figures for endoscopic ultrasound-fine needle aspiration were 80, 86 and 82%. There was good agreement with final diagnosis for endoscopic ultrasound-fine needle aspiration (kappa 0.673, 95%CI 0.592-0.753), greater than that for endoscopic ultrasound alone (kappa 0.515, 95%CI 0.425-0.605). There was one case of intracystic haemorrhage and one case of transient hyperthermia (0.3%). CONCLUSIONS: Endoscopic ultrasound-fine needle aspiration of pancreatic masses seems to be feasible, effective and safe in this consecutive study of patients.

Barrett's oesophagus: long-term follow-up after complete ablation with argon plasma coagulation and the factors that determine its recurrence.

BACKGROUND: Argon plasma coagulation seems to be a promising technique for ablation of Barrett's oesophagus, yet few long-term efficacy data are available. AIM: To report on a long-term follow-up and the factors that determine the recurrence of intestinal metaplasia in a cohort of patients with non dysplastic, intestinal type Barrett's oesophagus, after complete ablation of the metaplastic mucosa with argon plasma coagulation. METHODS: Ninety-six patients underwent endoscopic argon plasma coagulation with adequate acid suppression obtained through a continuous omeprazole therapy (50 patients) or through laparoscopic fundoplication (46 patients). Complete ablation was achieved in 94 patients who underwent follow-up. Endoscopic and histological examinations were performed every 12 months. RESULTS: The median follow-up of the patients was 36 months (range 18-98). A recurrence of intestinal metaplasia was found in 17 patients (18%), with an annual recurrence rate of 6.1%. Neither dysplasia, nor adenocarcinoma were found during the follow-up. Through the use of logistic regression analysis, previous laparoscopic fundoplication was associated with a reduced recurrence rate of intestinal metaplasia (odds ratio 0.30, 95% confidence interval 0.10-0.93). CONCLUSIONS: The long-term recurrence of intestinal type Barrett's oesophagus was low after complete ablation with argon plasma coagulation. The control of oesophageal acidity acid exposure with laparoscopic fundoplication seems to reduce the recurrence rate.

The hazardous burden of Herpesviridae in inflammatory bowel disease: the case of refractory severe ulcerative colitis.

BACKGROUND: Herpesviridae infection or spread may be a hazard in immunodepressed patients. In the field of inflammatory bowel disease, refractory severe ulcerative colitis is a challenging condition, closely associated to immunosuppression both for inanition due to the disease activity and for immunosuppressive treatments. Cytomegalovirus (CMV) has been proposed as a major cause of refractoriness, while other Herpesviridae may be a risk factor in the long-term follow-up. AIM OF THE STUDY: To evaluate the positivity rates of CMV, Epstein-Barr (EBV) and Human herpes virus-8 (HHV8) in a consecutive group of ulcerative colitis patients who underwent colectomy for refractoriness to medical treatment compared to a control group, using state of the art methods. PATIENTS AND METHODS: Colonic specimens from 24 consecutive patients with ulcerative colitis submitted to colectomy for refractoriness and from 20 controls (submitted to colectomy for colorectal cancer) were studied. Standard histology and immunohistochemistry (IHC) for CMV and specific polymerase chain-reaction (PCR) for CMV, EBV and HHV8 were carried out. RESULTS: Regarding CMV, 1 case (4%) was positive at histology and IHC, whereas 3 cases (13%) were positive at PCR, compared to none in the control group (p=0.239). For EBV 2 cases (8%) and 2 controls (10%) were positive at PCR. None of the cases or of controls was positive for HHV8. The only clinical characteristic independently associated to CMV positivity was the white blood cell count at admission, higher among CMV positive patients (p<0.001). At the end of the post-surgery follow-up (median 7.3 years) none of the CMV positive cases experienced pouchitis, compared to 3/21 (14%) of the CMV negative cases (p=1.000). DISCUSSION: Our data suggest that CMV is uncommon (13%), even though PCR techniques, considered to be the most sensitive tools, were used for virus detection and the study population is made by highly selected patients with definite refractoriness. EBV and HHV8 may represent a theoretical risk of immunosuppressive therapy because of their potential role as cancer triggers; however in our study, results seem to be reassuring that UC patients undergoing immunosuppressive therapy are not exposed to an excessive risk of viral infection.

Multicentre retrospective study on endoscopic ultrasound complications.

BACKGROUND: Endoscopic ultrasonography, both conventional and interventional, has been used increasingly during the past 20 years and is deemed a safe technique. Its complication rate, however, has been studied to only a limited extent. This multicentre investigation sought to establish the complication rate for a large number of endoscopic ultrasonography procedures. METHODS: By means of a questionnaire, we collected data from six centres on the number of endoscopic ultrasonography examinations performed and divided them into conventional and interventional examinations of the upper and lower gastrointestinal tract. Information was obtained on technical modalities such as instruments and sedation and, for interventional endoscopic ultrasonography, indications, pre-procedural exams and technical details (needle calibre, number of passes) had to be specified. Complications were classified as mild, moderate, severe or fatal and their onset as immediate, early or late. Variables that entered into the analysis of complication rate included type of endoscopic ultrasonography instrument used, type and site of lesion biopsied, number of needle passes and operator experience. RESULTS: Eleven thousand five hundred thirty nine endoscopic ultrasonographic procedures were reported, of which 10,731 were conventional and 808 interventional. No deaths occurred; there were 14 (0.12%) complications, 5 (0.046%) of them following conventional endoscopic ultrasonography and 9 (1.11%) after interventional endoscopic ultrasonography. Seven complications were mild, four moderate and three severe. CONCLUSIONS: Both conventional and interventional endoscopic ultrasonography were confirmed to be acceptably safe techniques.

Serum bile acids, programmed cell death and cell proliferation in the mucosa of patients with colorectal adenomas.

BACKGROUND: Deoxycholic acid induced programmed cell death and an imbalance with cell proliferation may favour colorectal tumourigenesis according to 'in vitro' studies, but information is lacking on the relationships occurring 'in vivo' in humans. AIMS: To evaluate whether serum deoxycholic acid is associated with programmed cell death and cell proliferation in colonic mucosa. METHODS: In 10 patients with colorectal adenomas, we measured fasting serum levels of bile acids; and, in normal colonic mucosa, programmed cell death by the TUNEL technique and cell proliferation by immunohistochemical staining with anti-Ki67. Total and compartmental indices for both activities were calculated. RESULTS: Among serum bile acids, only total deoxycholic acid (median: 0.89 micromol/L +/- 0.54 95% CI), showed a significant positive correlation with the total and basal compartments PCD Index (r = 0.68, p < 0.05). Total proliferation index showed no correlation with either total PCD Index, or bile acids. Within the median compartment of the crypt, cell proliferation was negatively associated with all unconjugated bile acids. CONCLUSIONS: The positive association between deoxycholic acid and programmed cell death in the basal compartment of the crypt, and the negative association of cell proliferation and unconjugated bile acids in the median compartment, do not seem to support the co-carcinogenic effect of deoxycholic acid.

A microcosm approach to assessing the effects of earthworm inoculation and oat cover cropping on CO2 fluxes and biological properties in an amended semiarid soil.

We designed a microcosm experiment to assess the influence of inoculation with Eisenia foetida earthworms and the establishment of an Avena sativa cover crop on biological (enzyme activities and labile carbon fractions) soil quality indicators in a soil treated with a composted organic residue, and to determine the contribution of these treatments to carbon dioxide emissions from the soil to the atmosphere of the microcosm. The microcosms were incubated for 53 days under 28 degrees C/18 degrees C day/night temperatures. The addition of earthworms and the planting of A. sativa increased dehydrogenase activity of compost amended soil by about 44% after 23 days of incubation. The metabolic potential, calculated as the ratio dehydrogenase activity/water soluble C, was higher in the compost amended soil planted with A. sativa. The highest total amount of CO2-C evolved occurred in the soil treated with composted residue and earthworms (about 40% of the total amount of CO2 evolved came from earthworm activity). The planting of A. sativa increased the decomposition rate constant of organic matter in the amended soil but decreased the potentially mineralizable C pool. In conclusion, the establishment of an A. sativa cover crop and the addition of E. foetida to a degraded agricultural soil treated with composted residue were effective treatments for improving the biological and biochemical quality and the metabolic potential of the soil.

A convenient method for the stereoselective conversion of aryl peptidyl ketones into the corresponding aryl aminomethin derivatives, a novel class of modified peptides.

In this paper we describe a reductive amination procedure that can be employed in the preparation of a novel class of pseudopeptides in which a specific amide bond is replaced by a CH(Ar)NH group. The developed methodology, performed using NaBH(3)CN and TiCl(4), is characterized by the formation of diastereomeric intermediates in a relative 1:1 ratio. It provides aryl aminomethin pseudopeptides in moderate but satisfactory yields and with definite stereochemistry on the asymmetric centres next to the modified peptide bond.

Therapeutic ERCP in paediatric patients.

BACKGROUND: Major limitations of endoscopic retrograde cholangiopancreatography in paediatric populations are a low incidence of biliopancreatic disease among children, the equipment dimensions (size of endoscopes and devices) and the increasing role of MR-cholangiopancreatography in the field of diagnostic indications. Aim of this study was to evaluate the diagnostic and therapeutic yields of endoscopic retrograde cholangiopancreatography for biliopancreatic diseases in a paediatric population. METHODS: Between 1996 and 2002, 48 endoscopic retrograde cholangiopancreatographies were performed in 38 children aged 4 weeks to 17 years as part of the diagnostic evaluation for suspected pancreatic or biliary tract disease. Endoscopic retrograde cholangiopancreatography was carried out under general anaesthesia, using prototype paediatric duodenoscopes or standard duodenoscopes in children younger or older than 18 months, respectively. RESULTS: The indications to perform endoscopic retrograde cholangiopancreatography were common bile duct stones (14 children), biliopancreatic abnormalities (8), primary sclerosing cholangitis (2), Wirsung disruption (1), biliary leakage (1), cholestasis (4) and pancreatitis (8). Cannulation was successful in all patients but one. Sphincterotomy together with stone extraction or stent insertion was performed in 30/38 patients. Immediate complications were mild and treated conservatively. CONCLUSIONS: Diagnostic and therapeutic endoscopic retrograde cholangiopancreatography can be used safely and effectively in the management of biliopancreatic diseases in childhood as well. Indications, endoscopic techniques and complications are similar to those reported for adult patients.

[Occupational exposure to endocrine disruptors: state of the art]. / Esposizione professionale a distruttori endocrini: stato dell'arte.

Research into how exposure to "endocrine disrupters chemicals" affects human health is attracting increasing attention among European and international scientists since these contaminants are so widespread in the home and work environment and can have far-reaching effects on mental and physical health. Here we draw a general picture of studies to date on specific occupational exposures to single chemicals such as bisphenol A, styrene, etc., or homogeneous groups such as pesticides, metals, dioxins, phthalates and others. Although the exposure occurs in different ways, the toxic mechanisms of action vary widely, and it is hard to establish precisely the conditions of occupational exposure, significant correlations are nevertheless evident between the potential dose and its effects and further studies are certainly needed. There is still much debate on the epidemiological methods employed, which may overestimate exposure. The "measure" or at least an accurate description of exposure conditions is critical to the whole question and attempts to ensure this involve standardized procedures and statistical tests as the basis for a protocol for assessing the risk of occupational exposure. Investigations to date have focused on the effects on the reproductive system, in males in particular. However, considering the broad range of equilibria and systems on which endocrine destructive compounds can act, the international scientific community needs to persist in its efforts to develop methods for checking the effects on other endocrine organs--particularly the thyroid gland--and on the immune and neurological systems.

Coeliac disease associated with Sjögren's syndrome, renal tubular acidosis, primary biliary cirrhosis and autoimmune hyperthyroidism.

Although coeliac disease may occur in patients affected by another immune-mediated disorder, its coexistence with multiple autoimmune diseases is not frequently described. We report here the case of a 45-year-old woman referred to our centre because of diarrhoea and weight loss, who had already received a diagnosis of primary biliary cirrhosis, Sjögren's syndrome and renal tubular acidosis. Following the development of diarrhoea we established the diagnosis of coeliac disease, based on the presence of anti-endomysium antibodies and a compatible duodenal biopsy. Despite gluten withdrawal she went on to develop an autoimmune hyperthyroidism. The patient tested positive for HLA DRB1*03 and DQB1*02. The association is unlikely to be casual and may be explained by autoimmune mechanisms, genetic susceptibility and favouring environmental factors commonly shared by the diseases of our patient.

An efficient and highly selective deprotection of N-Fmoc-alpha-amino acid and lipophilic N-Fmoc-dipeptide methyl esters with aluminium trichloride and N,N-dimethylaniline.

A novel procedure for the deprotection of the carboxyl group of amino acid methyl esters is presented. The process is carried out by the reagent system aluminium trichloride/N,N-dimethylaniline that can successfully be applied to unblock the carboxyl moiety either of N-Fmoc-protected amino acid methyl esters and N-Fmoc-protected short dipeptide methyl esters. The chiralities of the optically pure amino acid or peptide precursors are maintained totally unchanged.