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.

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.

Severe imbalance of cell proliferation and apoptosis in the left colon and in the rectosigmoid tract in subjects with a history of large adenomas.

BACKGROUND: Alterations in epithelial proliferation and apoptosis in colonic mucosa are associated with an increased risk of colon cancer. It is unclear if these alterations represent a generalised "field defect". AIMS: To analyse segmental patterns of cell proliferation and apoptosis in the colon of subjects with a high and no apparent risk of colon cancer. METHODS: Pancolonoscopy was performed in 15 patients with resected adenomas (> or =1.5 cm) and in nine subjects without an apparent risk of colorectal cancer. Mucosal biopsies were taken from the right colon, left colon, and sigmoid rectum. Crypt cell proliferation and apoptosis were evaluated, respectively, with bromodeoxyuridine immunohistochemistry and terminal deoxyuridine nucleotidyl nick end labelling of DNA strand breaks. Results are expressed as total labelling index (TLI) and labelling index (LI) for each of the five compartments in which colonic crypts were divided (fourth and fifth compartments were evaluated together) for cell proliferation and as apoptotic index (AI) for apoptosis assessment. RESULTS: No significant segmental variations in proliferation were found in either group. Compared with controls, adenoma patients had higher TLIs for the right (p>0.05), left (p<0.005), and sigmoid rectum (p<0.05) segments, and higher left colon LIs for crypt compartments (compartment 1, p<0.01; compartment 2, p<0.005; compartment 3, p<0.001; compartments 4-5, p<0.01). Control AIs were similar in all segments but in the adenoma patients left colon and sigmoid rectum AIs were lower than their right colon indexes (p<0.05, p<0.05) and corresponding values for controls (p<0.01, p<0.05). CONCLUSIONS: The colonic mucosa of patients with past adenomas presents diffuse hyperproliferation and, distally, abnormally distributed proliferating cells and markedly reduced apoptosis. These changes represent a significant risk for malignancies and could account for the high prevalence of left colon tumours.

Esophageal dysmotility and gastroesophageal reflux in intrinsic asthma.

This study was undertaken to determine the prevalence of esophageal motor abnormalities, the incidence of gastroesophageal reflux, and the coexistence of gastroesophageal reflux with esophageal dysmotility in patients with intrinsic asthma. Based on clinical criteria, 34 consecutive asthmatics, 15 patients with gastroesophageal reflux, and 10 subjects with upper gastrointestinal symptoms with normal results of esophageal manometry and 24-hr esophageal pH test (controls) were studied. Esophageal motor disorders were noted in 23 of 34 asthmatics, and in 10 of 15 patients with acid reflux but in none of the subjects of the control group. A positive result of the prolonged esophageal pH study (pH in the distal esophagus less than 4 for more than 4.2% of the recording time) was obtained in 14 of 17 patients with asthma (only 17 of the original patients were tested because the others did not give informed consence for this test) and in all patients with gastroesophageal reflux. None of the members of the control group had positive test results. The findings of this study show that: (1) it is possible to identify a group of subjects with nonallergic asthma presenting with esophageal dysmotility, (2) the 24-hr esophageal pH study must be properly done in such patients; (3) esophageal motor abnormalities are often associated with positive pH results; and (4) more reflux was observed while in a supine position (especially during the night) than that observed either in control or reflux patients. Based on these results, patients with intrinsic asthma with reflux can benefit from both acid suppressive and prokinetic drugs with notable clinical implications regarding standard treatment for asthma, and those with prevalent supine compared to upright reflux could even benefit from surgery.

Isolation and characterization of a gene encoding alpha-tubulin from Candida albicans.

A gene encoding the alpha-tubulin of Candida albicans has been cloned and characterized. Nucleotide sequence analysis reveals the presence of an intron within the structural gene and predicts the synthesis of a polypeptide of 448 amino acid residues. Comparison of nucleotide and amino acid sequences with the Saccharomyces cerevisiae alpha-tubulin encoding genes shows a 75% homology and about 92% similarity respectively. In contrast to S. cerevisiae, C. albicans appears to possess only one gene for alpha-tubulin which is able to functionally complement a S. cerevisiae cold-sensitive tub1 mutant.

Plain film identification of inverted Meckel diverticulum.

Inversion is a potentially serious complication of Meckel diverticulum. Since inversion provokes gangrene and small bowel obstruction, diagnosis by enteroclysis or imaging studies can conflict with the need for timely surgical intervention. We have noted that plain films may predict this lesion when a solitary mottled polypoid lesion occupies the ileum at the site of a small bowel obstruction.