Low dose infliximab for prevention of postoperative recurrence of crohn's disease: Long term follow-up and impact of infliximab trough levels and antibodies to infliximab

Objective In patients with postoperative recurrence of Crohn's disease endoscopic and clinical remission can be maintained for up to 1 year with low infliximab doses (3 mg/Kg). However, in theory low-dose infliximab treated patients could develop subtherapeutic trough levels, infiximab antibodies, and might loose response to therapy. To verify this hypothesis infliximab pharmacokinetics and clinical/endoscopic response were checked in a group of patients treated in the long term with low infliximab doses. Design Infliximab antibodies, infliximab levels, highly-sensitive CRP and fecal calprotectin were measured during the 8-week interval in 5 consecutive patients in clinical (Crohn's Disease Activity Index < 150) and endoscopic (Rutgeerts scores 0-1) remission after one year of therapy with infliximab 3 mg/Kg. For comparison with reported standards, infliximab pharmacokinetics and inflammatory parameters were also tested in 6 Crohn's disease patients who did not undergo surgery and who were in clinical remission while on infliximab 5 mg/ Kg. Patients on low infliximab dose also underwent colonoscopy after 18 additional months of therapy. Results Highly sensitive CRP and fecal calprotectin increased in all patients during the 8-week interval. Infliximab trough levels were lower in patients treated with the low dose compared to controls (mean\ub1SE: 2.0\ub10.3 vs 4.75\ub10.83 \uceg/mL respectively p<0.05). Infliximab antibodies were present in two of the subjects treated with low infliximab dose and in none of the controls. However, in low dose-treated patients after 18 additional months of therapy endoscopy continued to show mucosal remission and none of them developed clinical recurrence or side effects. Conclusions Patients treated with low infliximab doses had lower trough levels compared to patients treated with 5 mg/Kg and some developed antibodies to infliximab. However, low infliximab doses sustained clinical and endoscopic remission for a total of 30 months of treatment

Prospective validation of the CLIP score: a new prognostic system for patient with cirrhosis and hepatocellular carcinoma

Prognosis of patients with cirrhosis and hepatocellular carcinoma (HCC) depends on both residual liver function and tumor extension. The CLIP score includes Child-Pugh stage, tumor morphology and extension, serum alfa-fetoprotein (AFP) levels, and portal vein thrombosis. We externally validated the CLIP score and compared its discriminatory ability and predictive power with that of the Okuda staging system in 196 patients with cirrhosis and HCC prospectively enrolled in a randomized trial. No significant associations were found between the CLIP score and the age, sex, and pattern of viral infection. There was a strong correlation between the CLIP score and the Okuda stage, As of June 1999, 150 patients (76.5%) had died. Median survival time was 11 months, overall, and it was 36, 22, 9, 7, and 3 months for CLIP categories 0, 1, 2, 3, and 4 to 6, respectively. In multivariate analysis, the CLIP score had additional explanatory power above that of the Okuda stage. This was true for both patients treated with locoregional therapy or not. A quantitative estimation of 2-year survival predictive power showed that the CLIP score explained 37% of survival variability, compared with 21% explained by Okuda stage. In conclusion, the CLIP score, compared with the Okuda staging system, gives more accurate prognostic information, is statistically more efficient, and has a greater survival predictive power. It could be useful in treatment planning by improving baseline prognostic evaluation of patients with RCC, and could be used in prospective therapeutic trials as a stratification variable, reducing the variability of results owing to patient selection

Study Design.

<p>Patients subjected to prophylactic infliximab [IFX] 5 mg/Kg after surgery and in full remission after 3 years of therapy showed endoscopic recurrence in 83% of cases when the medication was stopped. Those with recurrence (n = 10) re-started IFX in a dose optimization study in which we showed that 3 mg/Kg were sufficient to re-induce and maintain endoscopic remission for 1 year in all patients (ref.2). Five of these ten patients participated in the current study. Antibodies To Infliximab [ATI] and Infliximab Trough Levels [ITL] were measured and compared to those of CD patients who did not undergo surgery in remission on a standard 5 mg/Kg IFX dose. After an additional 18 months the patients treated with 3 mg/Kg IFX underwent colonoscopy.</p

Effects of nizatidine on gastric acid and bicarbonate secretion

The effects of nizatidine on human gastric parietal secretion (volume and acid output) and nonparietal secretion (volume and bicarbonate concentration and secretion) were evaluated in 18 patients with duodenal ulcer. Nizatidine reduced the volume of pentagastrin-stimulated gastric secretion and gastric acid secretion. Nizatidine also decreased the volume of nonparietal secretion and bicarbonate secretion, although bicarbonate concentration remained unchanged. © 1993 Excerpta Medica, Inc. All rights reserved

Serum pepsinogens as markers of Helicobacter pylori eradication

Various methods, both invasive and noninvasive, are used to verify Helicobacter pylori eradication, with varying degrees of accuracy. The purpose of this study was to verify the relationship between H pylori eradication and serum levels of pepsinogen A (PGA) and pepsinogen C (PGC). The study involved 79 patients who tested positive for H pylori infection after histologic examination and the urease test. Patients were treated with various drug regimens for 7 to 25 days. Two months after discontinuing treatment, endoscopy was performed to verify H pylori eradication; 33 of 79 patients were found to be free of infection. Venous blood samples were taken to measure PGA and PGC levels before and after treatment. Patients in whom H pylori infection was eradicated had a significant drop in PGA and PGC levels, whereas in patients with persisting H pylori infection, there was a trend in which pepsinogen levels coincided with the quantity of bacteria detected. These preliminary data suggest that it may be possible to evaluate H pylori eradication by means of serum pepsinogen levels, sparing patients a follow-up endoscopy. © 1995

Do concomitant diseases and therapies affect the persistence of ulcer symptoms in the elderly?

Risk factors of slow healing were previously researched in a large sample of duodenal (DU) and gastric ulcer (GU) patients over 65 years of age; persistence of ulcer symptoms was proven the most reliable factor in predicting nonhealing ulcer, while ulcer size was of importance only for DU. We aimed to complete the analysis, with a more careful evaluation of concomitant diseases and therapies. Ranitidine 300 mg daily was given for four to eight weeks to 310 GU and 699 DU patients. Ninety-three patients dropped out of the study; 79/294 gastric ulcers and 138/635 duodenal ulcers were unhealed after four weeks. Cardiovascular, gastrointestinal, and pulmonary disorders were the most frequent concomitant diseases; NSAIDs, cardiovascular drugs, and antihypertensives were the most frequent concomitant therapies. Esophagitis was diagnosed in 15.5% of patients. Ulcer healing was the major determinant of persistence of ulcer symptoms; esophagitis emerged as an important adjunctive and independent factor. Use of hypoglycemic agents in the whole sample and smoking habit (in GU) may have also a role. With persistence of ulcer symptoms removed from the analysis, ulcer size was the most constant factor affecting ulcer healing. NSAID use, cardiovascular disorders, esophagitis (in GU), and concomitant therapy with cardiovascular drugs (in DU) also play a role. In conclusion, persistence of ulcer symptoms, the major indicator of slow ulcer healing in the elderly, is independently affected also by the presence of esophagitis. Use of hypoglycemic agents and smoking habit may also have a role in persistence of ulcer symptoms. NSAIDs, cardiovascular disorders, cardiovascular drugs, and esophagitis affect ulcer healing, for which the most constant indicators remained persistence of ulcer symptoms and ulcer size

BRAF gene copy number and mutant allele frequency correlate with time to progression in metastatic melanoma patients treated with MAPK inhibitors

Metastatic melanoma is characterized by complex genomic alterations, including a high rate of mutations in driver genes and widespread deletions and amplifications encompassing various chromosome regions. Among them, chromosome 7 is frequently gained in BRAF-mutant melanoma, inducing a mutant allele-specific imbalance. Although BRAF amplification is a known mechanism of acquired resistance to therapy with MAPK inhibitors, it is still unclear if BRAF copy-number variation and BRAF mutant allele imbalance at baseline can be associated with response to treatment. In this study, we used a multimodal approach to assess BRAF copy number and mutant allele frequency in pretreatment melanoma samples from 46 patients who received MAPK inhibitor-based therapy, and we analyzed the association with progression-free survival. found that 65% patients displayed BRAF gains, often supported by chromosome 7 polysomy. In addition, we observed that 64% patients had a balanced BRAF-mutant/wild-type allele ratio, whereas 14% and 23% patients had low and high BRAF mutant allele frequency, respectively. Notably, a significantly higher risk of progression was observed in patients with a diploid BRAF status versus those with BRAF gains [HR, 2.86; 95% confidence interval (CI), 1.29-6.35; P = 0.01] and in patients with low percentage versus those with a balanced BRAF mutant allele percentage (HR, 4.54; 95% CI, 1.33-15.53; P = 0.016). Our data suggest that quantitative analysis of the BRAF gene could be useful to select the melanoma patients who are most likely to benefit from therapy with MAPK inhibitors. (C) 2018 AACR

Le manifestazioni extraepatiche del virus dell'epatite C: inquadramento e gestione clinica

Printed from http://www.webaisf.org target=NewWindow>www.webaisf.org (February 2005)Consiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7 , Rome / CNR - Consiglio Nazionale delle RichercheSIGLEITItal