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.

Multiple Perianal Ulcers Related to Use of a Hemorrhoidal Ointment With the Active Ingredients Triamcinolone Acetonide, Lidocaine, and Pentosan Polysulfate Sodium: A Series of 11 Spanish Patients. / Múltiples úlceras perianales en relación con el uso de una pomada antihemorroidal con acetónido de triamcinolona, lidocaína y pentosano polisulfato sódico como principios activos: una serie de 11 pacientes españoles.

The development of perianal ulcers related to the use of a hemorrhoidal ointment has not been reported in the literature. We describe a series of 11 patients who were treated for perianal ulcers in 10 Spanish hospitals after they used the same ointment containing the active ingredients triamcinolone acetonide, lidocaine, and pentosan polysulfate sodium. No prior or concomitant conditions suggesting an alternative cause for the condition could be identified, and after the patients stopped using the ointment, their ulcers cleared completely in 8 weeks on average. This case series shows the damage that can be caused by an over-the-counter pharmaceutical product used without medical follow-up. It also illustrates the need to ask patients with perianal ulcers about any topical agents used before the lesions appeared.

Randomised clinical trial: mesalazine and/or probiotics in maintaining remission of symptomatic uncomplicated diverticular disease--a double-blind, randomised, placebo-controlled study.

BACKGROUND: Placebo-controlled studies in maintaining remission of symptomatic uncomplicated diverticular disease (SUDD) of the colon are lacking. AIM: To assess the effectiveness of mesalazine and/or probiotics in maintaining remission in SUDD. METHODS: A multicentre, double-blind, placebo-controlled study was conducted. Two hundred and ten patients were randomly enrolled in a double-blind fashion in four groups: Group M (active mesalazine 1.6 g/day plus Lactobacillus casei subsp. DG placebo), Group L (active Lactobacillus casei subsp. DG 24 billion/day plus mesalazine placebo), Group LM (active Lactobacillus casei subsp. DG 24 billion/day plus active mesalazine), Group P (Lactobacillus casei subsp. DG placebo plus mesalazine placebo). Patients received treatment for 10 days/month for 12 months. Recurrence of SUDD was defined as the reappearance of abdominal pain during follow-up, scored as ≥5 (0: best; 10: worst) for at least 24 consecutive hours. RESULTS: Recurrence of SUDD occurred in no (0%) patient in group LM, in 7 (13.7%) patients in group M, in 8 (14.5%) patients in group L and in 23 (46.0%) patients in group P (LM group vs. M group, P = 0.015; LM group vs. L group, P = 0.011; LM group vs. P group, P = 0.000; M group vs. P group, P = 0.000; L group vs. P group, P = 0.000). Acute diverticulitis occurred in six group P cases and in one group L case (P = 0.003). CONCLUSION: Both cyclic mesalazine and Lactobacillus casei subsp. DG treatments, particularly when given in combination, appear to be better than placebo for maintaining remission of symptomatic uncomplicated diverticular disease. (ClinicalTrials.gov: NCT01534754).

[Comparison of sevoflurane and propofol in the maintenance of and recovery from anesthesia]. / Comparación entre sevoflurano y propofol en el mantenimiento y recuperación de la anestesia.

OBJECTIVE: To compare the recovery of patients after anesthesia with sevoflurane or propofol during open urological surgery or lumbar column surgery of intermediate duration. PATIENTS AND METHODS: Thirty-six ASA I, II or II patients were enrolled prospectively and randomly assigned to two groups to receive either sevoflurane (n = 19) or proporol (n = 17). Anesthetic induction was accomplished with thiopental, fentanil and vecuronium. During anesthetic maintenance a mixture of 60% nitrous oxide in oxygen plus the drug under study was adjusted to keep blood pressure and/or heart rate within +/- 20% of baseline. After surgery we recorded time until eye opening, spontaneous breathing, extubation, orientation, and identification of parts of the body. Side effects were likewise recorded. In the postanesthetic recovery ward patient condition was assessed using the Aldrete scale, the Newman-Trieger test and a visual analog scale for postoperative pain. Consumption of analgesic during the first 24 h after surgery was monitored. RESULTS: No significant differences were found in demographic data; duration of anesthesia; anesthetic doses; or time until spontaneous breathing, extubation, orientation or identification of parts of the body. Only time until eye opening was shorter in the sevoflurane group than in the propofol group (6.9 +/- 3.3 vs 11.5 +/- 4.8 min; p < 0.05). No differences were recorded on scales reflecting intermediate-term recovery. Analgesic consumption and the incidence of side effects were similar in both groups. CONCLUSIONS: Sevoflurane and propofol are comparable for anesthetic maintenance in urological and neurological procedures of intermediate duration.

[Prevalence and features of peptic ulcers in the elderly: a retrospective study on a not hospitalized population aged 65 or over]. / Caratteristiche e prevalenza dell'ulcera peptica nell'anziano: studio endoscopico retrospettivo su una coorte di pazienti ultrasessantacinquenni non istituzionalizzati.

BACKGROUND: The prevalence of peptic ulcer increases with aging. Data relative to peptic ulcer in the elderly are around 5.2% to 9.9%. The aim of the present study was to evaluate the prevalence and the features of peptic ulcer in a non hospitalized population aged 65 or over. METHODS: We performed, for the first time, EGDS on 706 patients with symptoms related to the superior gastroenteric tract. We considered the following risk factors: familiarity for peptic disease, habits, eventual use of FANS, infection of Hp. RESULTS: Our data show that peptic ulcer increases with aging and with physiopathological age-related changes. 114 (16.1%) patients were affected by DU; 84 (11.9%) patients were affected by GU Symptoms thereafter were not clear: epigastralgy was present in 46.4% of patients affected by GU; pyrosis, belchings, swellings, epigastric headness were present in 37.7% of patients with DU. Several times PU may arise with some complications: melena was present in 14.9% of patients with DU vs 11.9% of patients with GU, hematemesis was present in 1.7% of patients with DU vs 5.9% of patients with G.U. The most important risk factor was the infection of Hp, at was present in 71.9% patients with GU and 81.6% patients with DU FANS assumption, often with high dose, was present in 30.9% of patients with GU and 18.4% of patients with DU.

[Early gastric cancer. Survival and prognostic factors in 95 consecutive cases]. / Early gastric cancer. Sopravvivenza e fattori prognostici in 95 casi consecutivi.

In order to characterize prognostic factors and therapeutic strategies for EGC, we have studied 95 patients operated on from 1980 to 1988. EGC was limited to the mucosa in 36% and extended to the submucosa in 64% of the cases. Lymph nodes involvement was observed in 13 patients; in 12 of them EGC extended to the submucosa. Gastric resection was performed in 73 and total gastrectomy in 22 patients with a postoperative mortality of 6% and 16% respectively. During the follow-up 8 patients died for causes related to EGC, 8 for unrelated causes. The 5 years survival rate was 79, without differences according to site, type, size and histology of EGC, lymph nodes involvement, type of gastrectomy; only EGC limited to the mucosa was associated with a better survival experience (96% vs 70% of tumors extended to the submucosa p less than 0.05). The prognosis of EGC is good and a curative surgery may be accomplished, especially if the lesion is limited to the mucosa. In EGC extended to the submucosa an accurate lymphadenectomy may further improve the prognosis, while total gastrectomy--de principe--carries a higher postoperative mortality, without significant improvement of the long term prognosis.

Bile and biliary lipid secretion in rats with hexachlorobenzene-induced porphyria. Effect of S-adenosyl-L-methionine administration.

We investigated liver morphology and biliary function in vivo in rats made porphyric by hexachlorobenzene (HCB). In one group of HCB rats we also evaluated whether S-adenosyl-L-methionine (SAMe), administered during the last 15 days of HCB treatment, attenuated liver injury and the accumulation of porphyrins (HCB + SAMe group). In HCB rats we found: (a) a 100% increase in liver weight; (b) a 500-fold increase in total liver porphyrins (TLP); (c) significantly increased serum bilirubin and cholesterol levels; (d) unchanged total bile flow (TBF) but enhanced levels of the bile acid independent fraction (BAIF); and (e) decreased excretion in bile of bile acids (BA), phospholipids (PL) and cholesterol (CHO) (58, 65 and 47%, respectively, expressed as mmol/min per kg liver). SAMe was found to partially reverse HCB-related effects. TLP levels were about 65% lower in HCB + SAMe treated rats than in HCB rats. However, while SAMe restored bile CHO excretion to control values, it did not influence bile excretion of BA, PL, or BAIF. In conclusion, HCB-induced porphyria was characterized by a complex derangement of liver morphology and biliary function that was unrelated to the extent of porphyrin accumulation in the liver.

Protective effect of S-adenosyl-L-methionine in hepatic uroporphyria. Evaluation in an experimental model.

The potential use of S-adenosyl-L-methionine (SAMe) as therapy for human porphyria cutanea tarda was investigated in an experimental model of hepatic porphyria--that is, chronic treatment of female rats with 0.2% hexachlorobenzene (HCB) in the diet. Administration of SAMe (25 mg/kg subcutaneously twice daily) during the last 15 days of HCB administration halved porphyrin accumulation in the liver but did not alter HCB-induced massive inhibition of uroporphyrinogen decarboxylase. Equally unaffected were inhibition of glutathione peroxidase and stimulation of lipid peroxide formation induced by HCB. Hypothetically, the beneficial effect of SAMe on hepatic porphyrin accumulation might be linked to modifications of the cellular availability of adenosine triphosphate.

Metabolic fate of plasma diamine oxidase: evidence of isolated and perfused rat liver uptake.

After injection of an intravenous bolus of heparin (15,000 IU) in two groups of subjects, 10 normal volunteers and 6 subjects with external biliary drainage, blood and urine samples were collected; in the latter group bile samples were collected also. All samples were assayed for diamine oxidase (DAO). Persistently high values of this enzyme were found in plasma of both populations after heparin stimulation, while no increase in enzymatic activity was detected in bile and urine. In order to confirm and support the hepatic clearance of DAO, liver uptake of the enzyme derived from porcine kidney, human plasma and human placenta was studied by perfusion of isolated rat liver. Disappearance curves of the enzyme derived from three different sources showed a prompt liver uptake: activity decreased by about 50% in 10 min (endocytic uptake) and a slower but constant reduction during the remaining 110 min of perfusion was observed. These data suggest the hypothesis of liver metabolism of plasma DAO.

Evaluation of heparin toxicity in the isolated and perfused rat liver.

A plasma increase of liver enzymes has been recently reported in patients receiving heparin therapy. In this study we have evaluated the toxic effect of heparin infusion in the whole rat and in the isolated and perfused rat liver. No variation of plasma enzymes was observed in heparin-treated rats (10 IU per gram body weight, daily for 12 days). The heparin addition in the perfusion medium (5,000 IU in all) has shown no difference in the kinetics of hepatic enzymes release and in the other parameters of liver function. These data do not confirm a liver-toxic effect of heparin in the rat.