Real-life efficacy and safety of Ustekinumab as second- or third-line therapy in Crohn's disease: results from a large Italian cohort study.

OBJECTIVE: Ustekinumab (UST) is an anti-IL12/23 antibody for the treatment of Crohn's Disease (CD). The aim of this study was to compare the efficacy and safety of UST in a large population-based cohort of CD patients who failed previous treatment with other biologics. PATIENTS AND METHODS: 194 CD patients (108 males and 86 females, mean age 48 years (range 38-58 years) were retrospectively reviewed. 147 patients were already treated with anti-TNFα (75.8%), and 47 (24.2%) patients were already treated with anti-TNFα and vedolizumab. Concomitant treatment with steroids was present in 177 (91.2%) patients. RESULTS: At week 12, clinical remission was achieved in 146 (75.2%) patients. After a mean follow-up of 6 months, clinical remission was maintained in 135 (69.6%) patients; at that time, mucosal healing was assessed in 62 (31.9%) patients, and it was achieved in 33 (53.2) patients. Three (1.5%) patients were submitted to surgery. Steroid-free remission was achieved in 115 (59.3%) patients. Both serum C-Reactive Protein and Fecal Calprotectin (FC) levels were significantly reduced with respect to baseline levels during follow-up. A logistic regression, UST therapy as third-line therapy (after both anti-TNFα and vedolizumab), FC >200 µg/g, and HBI ≥8 were significantly associated with lack of remission. Adverse events occurred in 5 (2.6%) patients, and four of them required suspension of treatment. CONCLUSIONS: UST seemed to be really effective and safe in CD patients unresponsive to other biologic treatments, especially when used as second-line treatment.

Spondylodiscitis (Andersson lesion) in psoriatic spondyloarthritis: a rare event successfully treated with an anti-TNF therapy.

Spondylodiscitis (Andersson lesion) is an infrequent and late complication of advanced ankilosing arthritis. Scanty data on the efficacy of anti-TNF therapy for these lesions are available. To our knowledge, only few cases of spondylodiscitis occurring in patients with psoriatic arthritis were reported in literature. We describe the case of a patient with psoriatic arthritis who early developed Andersson lesions successfully treated with infliximab plus methotrexate therapy.

Análise produtiva e econômica de suínos criados nos sistemas wean-to-finish e convencional de produção / Productive and economic analysis of pigs raised in wean-to-finish and conventional production systems

O modelo de produção de suínos denominado Wean-to-Finish (WF) é considerado uma alternativa que busca alcançar melhor desempenho produtivo, redução de estresse aos animais e melhorias na logística. Nesse sistema, os leitões são desmamados e transferidos diretamente a um galpão WF (creche-crescimento-terminação), onde permanecem até o abate. Com o objetivo de avaliar os comportamentos produtivo e econômico de suínos alojados no sistema WF em comparação ao sistema convencional de produção (CC), foram avaliados dois grupos de suínos provenientes das mesmas unidades produtoras de leitões, nascidos e desmamados na mesma semana. Um grupo foi alojado em uma creche do sistema convencional de produção (grupo CC), e o outro em um galpão WF adaptado (grupo WF), ambos em baias coletivas. Para análise de produção, foram calculados o consumo médio diário de ração (CMDR), o ganho de peso médio diário (GPMD) e a conversão alimentar (CA). Para análise econômica, foi determinado o custo por quilograma de ganho de peso vivo. Os dados foram submetidos à análise de variância utilizando-se o pacote estatístico SAS, previamente testados para normalidade dos resíduos pelo teste de Shapiro-Wilk, e as médias dos grupos comparadas pelo teste de Tukey (5%). Na fase de creche, o GPMD foi de 0,468 e 0,449, e a CA de 1,48 e 1,42 para os Grupos WF e CC, respectivamente. Nas fases de crescimento e terminação, o GPMD foi de 0,924kg no grupo WF e de 0,909kg no grupo CC. A conversão alimentar foi de 2,41 para ambos os grupos, não sendo diferentes estatisticamente entre si (P>0,05) nas diferentes fases de produção nos parâmetros analisados. No aspecto econômico, o grupo WF apresentou os menores custos, com diferença de R$ 0,08 por quilograma de ganho de peso vivo em comparação ao grupo CC. Os resultados do desempenho produtivo associado ao aspecto econômico indicam que o sistema WF pode ser uma alternativa viável dentro da cadeia produtiva de suínos.

The pig production model called "Wean-to-Finish" (WF) is considered an alternative to better productive performance, reducing stress to the animals and improvements in logistics. In this system, the piglets are weaned and transferred directly to a WF shed (nursery-grower-finisher), where they remain until slaughter. Aiming to evaluate the productive and economic behavior of pigs housed in the WF system compared to conventional production system (CC), two groups of pigs from the same sow farm, born and weaned in the same week were evaluated. One group was housed in a conventional nursery production system (CC group) and the other in a WF shed adapted (WF group), both in collective pens. For analysis of the average production, average daily feed intake (ADFI), average daily weight gain (ADWG) and feed conversion ratio (FCR) were calculated. For economic analysis the cost per kilogram of live weight gain was determined. Data were subjected to analysis of variance using the SAS statistical package, previously tested for normality of the residuals using the Shapiro-Wilk test, and the means of groups were compared by the Tukey test (5 %). In the nursery phase ADWG was 0.468 and 0.449, and the FCR was 1.48 and 1.42 for the WF and CC groups respectively. During the growing and finishing ADWG was 0.924kg in the WF group and 0.909 in the CC group. The FCR was 2.41 for both groups, not being statistically different from each other (P>0.05) at different stages of production in the analyzed parameters. In the economic aspect, the WF group had the lowest costs, with a difference of R$ 0.08 per kilogram of live weight gain compared to the CC group. The results of productive performance associated with the economic aspect indicate that the WF system can be a viable alternative in the pig production chain.

Efficacy and safety of endoscopic submucosal dissection for colorectal neoplasia: a systematic review.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) has been proposed for large colorectal lesions, due to the high risk of recurrence following endoscopic mucosal resection. However, data on the efficacy and safety of colorectal ESD are still controversial. The aim of the current systematic review was to assess the efficacy and safety of colorectal ESD. METHODS: A detailed Medline search of papers published during the period 1999-2010 was performed, using the search terms "Endoscopic submucosal dissection," "Colorectal neoplasia," "Colon," or "Rectum." Published studies that evaluated ESD for colorectal lesions were assessed using well-defined inclusion/exclusion criteria, including histological confirmation and surgery for complications. The process was independently performed by two authors. Forest plots on primary (i.e. histologically verified R0 resection and surgery for ESD complications) and secondary end-points were produced based on random-effect models. Heterogeneity was assessed using the I2 statistic. Risk for within-study bias was also ascertained. RESULTS: A total of 22 studies (20 Asian, two European) provided data on 2841 ESD-treated lesions. The per-lesion summary estimate of R0 resection rate was 88% (95%CI 82%-92%; I2=91%). At meta-regression, carcinoid vs. non-carcinoid series (R0 93% vs. 87%; P=0.04) and Asian vs. European series (R0 88% vs. 65%; P=0.03) appeared to explain the detected heterogeneity. The per-lesion summary estimate of surgery for ESD complications was 1% (95%CI 0%-1%) with a moderate degree of heterogeneity (I2=49%). However, subgrouping of these results according to histological tumor types was not available in the reviewed studies. CONCLUSIONS: ESD appeared to be an extremely effective technique to achieve R0 resection of large colorectal lesions. The very low rate of surgery for complications also shows the potential safety of this approach.

Investigation on Opisthorchis felineus occurrence and life cycle in Italy.

Opisthorchiasis is a fish borne parasitic infection caused by helminths of the genus Opisthorchis (Digenea, Opisthorchiidae), affecting humans and other fish-eating mammals. Despite Opisthorchis felineus was first described in Italy in 1884, no cases of human opisthorchiasis were reported in this country until 2004; from then on, 4 outbreaks due to this species have been recorded in Central Italy. Following the more relevant of these outbreaks, involving 34 people in August 2007, snails, fishes and fecal samples collected from the Bolsena and Bracciano lakes (Central Italy) were analyzed in order to define the cycle of O. felineus in the area and investigate its prevalence in the different hosts. Pools of 20-40 snails each (4983 specimens altogether) of the genus Bithynia were analyzed by PCR for parasite DNA detection. Eight hundred and ninety-four fish belonging to 12 species were collected from the two lakes and tested for metacercariae both by muscle compression and digestion techniques. Eighty-seven fecal samples of 5 putative definitive host species were collected very close to the two lakes and tested for parasite eggs detection by formalin-ethyl acetate concentration technique. Identification at the species level of metacercariae and eggs, respectively, from fish and stool was confirmed by PCR analysis and sequencing. O. felineus DNA was detected in 0.08% (overall minimum infection rate) of snails of the genus Bithynia from the two lakes. The tench, Tinca tinca, was the only fish found infested in both lakes (prevalence 88.5%). O. felineus eggs were found only in cat feces (prevalence 46.4%). The tench represents the only threat for the human consumption in the study area while Coregonus sp., the most economically important species for the local fishery and frequently consumed raw marinated, resulted to be not infected. The high prevalence recorded both in fish and in definitive host suggests a widespread and massive presence of the parasite in the area. Further studies are needed to better investigate the possible role of some cyprinids species as intermediate hosts, in order to check their safety for human consumption.

Heterogeneity among methicillin-resistant Staphylococcus aureus from Italian pig finishing holdings.

A survey for methicillin-resistant Staphylococcus aureus (MRSA) in finishing pig holdings was carried out in Italy in 2008. MRSA isolates were characterised by spa-, MLST-, SCCmec- and antimicrobial susceptibility typing. A prevalence of 38% (45/118, 95% CI 29.4-46.9%) positive holdings was observed. Eleven different spa-types were found among 102 MRSA isolates, clustering in lineages associated with farm animals (ST398, ST9, ST(CC)97 in 36 holdings) and humans (ST1, 7 holdings). Nine (7.6%) holdings were positive for two, three or four different and unrelated spa-types in various combinations. ST398 was the most prevalent lineage (33 positive holdings). The most prevalent spa-type was t899 (ST398), detected in 22 positive holdings. Three novel spa-types (t4794 of ST9; t4795 of ST97; t4838 of ST398) were detected. Ten holdings were positive for spa-type t1730, that proved to be a new single-locus variant of ST97, within the CC97 (ST1476). The most prevalent SCCmec was Type V (79 isolates), while Type IVb was found in 10 isolates. None of the isolates was positive for Panton-Valentine Leukocidin, while most of the t127 and t1730 isolates, one t4794, one t4795, and one t2922 were positive for LukE-LukD genes. All 64 antimicrobial susceptibility tested isolates were resistant to tetracyclines, with high resistance rates to trimethoprim (68.8%), erythromycin (60.9%), and ciprofloxacin (35.4%). All t127, ST1 isolates were resistant to tetracycline-ciprofloxacin-erythromycin. This survey provides the first report of MRSA ST1 and ST(CC)97 among pigs and the first report of MRSA ST9 from pigs in Europe. The presence of human-associated CA-MRSA (t127, ST1, SCCmec type V) in 6% holdings surveyed can represent an additional MRSA reservoir for infections in humans.

[The impact of vertebral fractures on quality of life in postmenopausal women with osteoporosis. Validity of the Italian version of mini-Osteoporosis Quality of Life Questionnaire.]. / Impatto sulla qualità della vita delle fratture vertebrali in donne in età postmenopausale affette da osteoporosi. Validità della versione italiana del mini-Osteoporosis Quality of Life Questionnaire.

BACKGROUND: Vertebral fracture is one of the most commonly occurring osteoporotic fractures. Vertebral fractures associated with osteoporosis are a major cause of pain in elderly people and may hardly affect patient's health-related quality of life (HRQOL), making this an important parameter for assessment in these patients. Studies comparing the performance of HRQOL instruments in osteoporosis are lacking. OBJECTIVES: The purposes of this study were to assess the effect of vertebral fractures on health HRQOL in post-menopausal women with osteoporosis and to investigate the validity of the Italian version of the mini-Osteoporosis Quality of Life Questionnaire (mini-OQOL) in a clinical setting. METHODS: Patients were divided into two study groups, according to fracture status: vertebral fractures (41 patients) and no vertebral fractures (27 patients). Baseline assessments of anthropometric data, medical history, and prevalent fracture status were obtained from all participants. All of the participants were evaluated using both disease-targeted mini-OQOL and QUALEFFO, generic instrument (EUROQoL), disability scale (Roland Morris Disability questionnaire- RMDQ) and chronic pain grade questionnaire. RESULTS: Vertebral fractures due to osteoporosis significantly decreases scores on physical function, socio-emotional status, clinical symptoms, and overall HRQOL. Both disease-targeted questionnaires showing an association between the number of prevalent vertebral fractures and decreased HRQOL. Significant correlations existed between scores of similar domains of mini-OQOL and the QUALEFFO, especially for symptoms, physical function, activities of daily living and social function. The receiver operating characteristic (ROC) curve analysis of mini-OQOL and the QUALEFFO indicated that both questionnaires were significantly predictive of vertebral fractures. Number of concomitant diseases presented a weak significant correlation with EUROQoL (p=0.041). CONCLUSIONS: Our study suggests that the patients with vertebral fractures due to osteoporosis have a relevant impairment in quality of life. Both disease-targeted questionnaires discriminated between patients with and without vertebral fractures though the mini-OQOL, originally developed to measure the effect of vertebral fractures on quality of life, showed slightly better discriminant power. The benefit of the mini-OQOL is that it is efficient, self administered, and requires 3-4 minutes to complete.

Active circulation of bluetongue vaccine virus serotype-2 among unvaccinated cattle in central Italy.

Several seroconversions occurring in 2002 among sentinel cattle during the bluetongue-vaccination campaign in Lazio and Tuscany (central Italy) led to the suspicion of vaccine-virus circulation. Therefore in 2003, 17 seroconverting sentinel herds were investigated for the characteristics of the virus involved. From these farms, 91 unvaccinated animals and 57 Culicoides pools were tested for the presence of the bluetongue vaccine virus (serotype-2) or other strains. The presence of vaccine virus serotype-2 was confirmed by PCR followed by restriction analysis in the whole blood of 17 unvaccinated sentinel cattle and 12 pools of Culicoides imicola or C. obsoletus. Of the 17 herds, five were positive only for vaccine virus serotype-2, four were positive for other strains and two for both the vaccine and other strains; the remaining premises were virologicaly negative. The vaccine virus serotype-2 also was detected in areas not included in the vaccination campaign.

Identification of Culicoides obsoletus (Diptera: Ceratopogonidae) as a vector of bluetongue virus in central Italy.

In 2001 and 2002, 235 outbreaks of bluetongue were observed in the Lazio and Tuscany regions of central Italy. During entomological surveillance Culicoides imicola, the main vector of bluetongue virus in the Mediterranean region, was detected in only 14 of 28 municipalities affected by outbreaks; Culicoides obsoletus was the most abundant species, contributing 83 per cent of individuals in catches, whereas C. imicola contributed only 2 per cent. In affected municipalities the maximum catch of C. obsoletus was 18,000 specimens, compared with 54 of C. imicola. In October 2002 bluetongue virus serotype 2 was isolated from a single pool of wild-caught, non-blood-engorged parous C. obsoletus inoculated on to BHK-21 cells. Its identity was confirmed by reverse transcriptase-PCR.

Development of recombinant capsid antigen/transmembrane epitope fusion proteins for serological diagnosis of animal lentivirus infections.

Among animal lentiviruses, Feline immunodeficiency virus (FIV), Equine infectious anaemia virus (EIAV) and Small ruminant lentiviruses (SRLV) are important pathogens associated with a variety of clinical pictures including immunodeficiency, anaemia, arthritis, pneumonia. The detection of viral antibody response represents a practical diagnostic approach in all lentivirus infections since they remain detectable long life. Capsid antigen (CA) is the major viral core protein and specific antibodies against this antigen are usually first recognised in infected sheep, goat and horse, remaining detectable for long period. Transmembrane (TM) domain of envelope glycoprotein contains a well conserved motif known to form an immunodominant epitope in several lentiviruses. In this study a simple strategy was developed to express the entire CA and the TM epitope in a single fusion protein from equine, feline and small ruminant lentiviruses in prokaryotic system and evaluated the diagnostic utility of a purified preparation in an indirect ELISA for each of the three infections. Results demonstrate that, for FIV and SRLV infections, the combination of CA and TM fractions increases the sensitivity of diagnostic tests based only on CA. The corresponding CA/TM antigen from EIAV showed excellent agreement with Coggins test.

An unusual endoscopic finding: Trichuris trichiura. Case report and review of the literature.

Detection of Trichuris trichiura during colonoscopic examination is an unusual finding, at least in developed countries. We report a case of a coincidental endoscopic diagnosis of whipworm infestation performed in a patient referred to our open-access endoscopy even before a faecal examination for ova and/or parasites had been performed. Review of literature on colonoscopic diagnosis of T. trichuria is provided.

A clinical practice viewpoint: to culture or not to culture Helicobacter pylori?

Bacterial culture has played an irreplaceable role in the discovery and characterisation of Helicobacter pylori. The main topic of the present article is to critically review the role of culture in the management of H. pylori infection in clinical practice, from diagnosis to treatment. The available data suggest that H. pylori culture is an invasive, time-consuming method, offering quite low sensitivity, requiring significant cost for the patient, and which, in practice, tests very few antibiotics, with a questionable contribution to the management of non-responder patients. Therefore, whether patients should undergo (and pay for) an upper endoscopy for bacterial culture remains a debatable matter.

A third-line levofloxacin-based rescue therapy for Helicobacter pylori eradication.

BACKGROUND: Helicobacter pylori infection persists in a considerable proportion of patients after both first- and second-line current treatments. A standard therapy for re-treatment in such refractory patients is still lacking. This study aimed to evaluate the efficacy of a levofloxacin-amoxycillin combination in patients who previously failed two or more therapeutic attempts. PATIENTS AND METHODS: Consecutive patients with persistent Helicobacter pylori infection were enrolled. Bacterial infection was assessed by rapid urease test and histology on gastric biopsies at endoscopy. Patients were assigned to receive a 10-day triple therapy, comprising rabeprazole 20 mg b.d., levofloxacin 250 mg b.d., and amoxycillin 1 g b.d. Four to 6 weeks after therapy, Helicobacter pylori eradication was assessed by a further endoscopy or 13C urea breath test. RESULTS: Overall, 36 patients were enrolled, but two patients were lost to follow-up. Helicobacter pylori was successfully cured in 30 patients, giving an 83.3% (95% CI=71.2-95.5) and 88.2% (95% CI=77.4-99) eradication rate at intention-to-treat and per protocol analysis, respectively. Compliance was good in all but two patients, who discontinued the treatment at 8 and 6 days, respectively, on account of glossitis. No major side-effects were reported, whilst 7 (20.1%) patients complained of mild side-effects. CONCLUSIONS: This study demonstrates that a 10-day levofloxacin-amoxycillin triple therapy is a safe and successful third-line therapeutic approach for Helicobacter pylori eradication.

Long-term outcome of endoscopic pneumatic dilatation in Crohn's disease.

BACKGROUND: To avoid multiple surgeries in stenosing Crohn's disease, pneumatic endoscopic dilatation has been introduced. The present study evaluated the long-term clinical outcome in Crohn's disease patients after endoscopic dilatation for ileal or neoileal strictures. PATIENTS AND METHODS: All Crohn's disease patients who underwent pneumatic dilatation of ileal or ileo-colonic strictures between January 1988 and December 2001 were invited to return for a clinical check-up in June 2002. Clinical, endoscopic and radiological reports were reviewed. Symptomatic relief from sub-occlusive symptoms without requiring surgery was considered as a positive outcome, whereas the requirement of surgery was regarded as an unfavourable outcome. Possible predictors of favourable outcome were analysed. RESULTS: Endoscopic dilatation was technically successful in 34/43 (79%) Crohn's disease patients, with a mean number of dilatations per patient of 3 +/- 3.13. During a mean follow-up of 63.7 +/- 44.6 months, a positive long-term outcome was observed in 18 (52.9%) patients, whereas surgery was necessary in the remaining 16 cases. The risk of surgery was distinctly higher within 2 years post-dilatation than in the next 2 years (26.4% versus 8.3%, respectively; P = 0.078). No clear clinical, endoscopic or radiological predictive factors for a successful outcome were identified. CONCLUSIONS: Endoscopic pneumatic dilatation is an effective and safe procedure to be applied to patients with stenosing Crohn's disease, offering a very long-term benefit in a sub-group of patients.

Gastric cardia inflammation: role of Helicobacter pylori infection and symptoms of gastroesophageal reflux disease.

OBJECTIVE: Although high prevalences of both chronic inflammation (carditis) and intestinal metaplasia at the gastric cardia have been reported, the pathogenesis is still unclear. This study assesses the role of Helicobacter pylori (H. pylori) infection and symptoms of gastroesophageal reflux disease (GERD) in these histological alterations. METHODS: Consecutive patients who underwent upper endoscopy were enrolled in the study, irrespective of their symptoms. Patients previously treated for H. pylori infection and those using proton pump inhibitors were excluded. Two biopsies were performed in the antrum, two in the gastric body, and two at the gastric cardia. All biopsies were used to look for H. pylori and for histological assessment. RESULTS: A total of 133 patients were enrolled. Carditis and intestinal metaplasia at the cardia were detected in 100 (75.2%) and in 18 (13.5%) patients, respectively. The H. pylori infection rate was significantly higher in patients with carditis than in those without it (87/100 vs 7/33; p < 0.0001), and was higher in those with intestinal metaplasia at the cardia than in those without it (17/94 vs 1/39; p = 0.03). Conversely, the prevalence of GERD symptoms was not significantly different between patients with and without carditis (34/100 vs 16/33; p = NS), and between those with and without intestinal metaplasia (5/50 vs 13/83; p = NS). Interestingly, the prevalence of both H. pylori (64/94 vs 39/94; p = 0.0005) and intestinal metaplasia (18/133 vs 4/133; p = 0.0042) in the gastric cardia was significantly higher than that in gastric body. CONCLUSION: According to our study data, the gastric cardia is frequently infected with H. pylori with consequent development of both carditis and intestinal metaplasia, whereas GERD does not seem to be involved in these histological changes.

A triple therapy regimen after failed Helicobacter pylori treatments.

BACKGROUND: Following standard triple therapy, up to 20% of patients require further Helicobacter pylori eradication treatment. Data regarding the efficacy of re-treatment in these patients are scarce. AIM: To evaluate the efficacy of a triple therapy after one or more consecutive treatment failures. METHODS: A total of 51 patients with persistent H. pylori infection after at least one unsuccessful standard 1-week regimen were enrolled in the study. H. pylori infection at entry was assessed by rapid urease test and histology on biopsies from the antrum and the corpus. Patients were given a 2-week triple therapy, comprising ranitidine bismuth citrate 400 mg b.d., tetracycline 500 mg t.d.s., and tinidazole 500 mg b.d. Ranitidine bismuth citrate was given during meals, whilst tetracycline and tinidazole was given after meals. Bacterial eradication was assessed by endoscopy (36 patients) or 13C-urea breath test (15 patients) 4-6 weeks after therapy had ended. RESULTS: All 51 patients completed the study and H. pylori eradication was achieved in 46, with an eradication rate of 90% (95% CI: 82-98). In detail, bacterial eradication was obtained in 96% of patients who had previously failed one course of clarithromycin-amoxicillin based triple therapy, in 88% patients who had failed a clarithromycin-tinidazole based triple therapy, in 83% patients who had failed both treatment schedules, and in the only patient who had failed three consecutive therapeutic attempts. Two patients took the therapy for 9 and 10 days instead of the full 14 day-course. No major side-effects were reported, whilst six (12%) patients complained of mild side-effects. CONCLUSION: This study demonstrates that this triple therapy regimen is effective for re-treatment of H. pylori infection.