Clinical activity after fingolimod cessation: disease reactivation or rebound?

BACKGROUND AND PURPOSE: There is debate as to whether the apparent rebound after fingolimod discontinuation is related to the discontinuation itself or whether it is due to the natural course of highly active multiple sclerosis (MS). Our aim was to survey the prevalence of severe reactivation and rebound after discontinuation of fingolimod in a cohort of Italian patients with MS. METHODS: Patients with relapsing-remitting MS who were treated with fingolimod for at least 6 months and who stopped treatment for reasons that were unrelated to inefficacy were included in the analysis. RESULTS: A total of 100 patients who had discontinued fingolimod were included in the study. Fourteen patients (14%) had a relapse within 3 months after fingolimod discontinuation, and an additional 12 (12%) had a relapse within 6 months. According to this study's criteria, 10 patients (10%) had a severe reactivation. Amongst these patients, five (5%) had a reactivation that was considered to be a rebound. CONCLUSIONS: The present study showed that more than 26% of patients are at risk of having a relapse within 6 months after fingolimod discontinuation. Nevertheless, the risk of severe reactivations and rebound is lower than has been previously described.

A multicenter, observational, prospective study of self- and parent-reported quality of life in adolescent multiple sclerosis patients self-administering interferon-ß1a using RebiSmart™-the FUTURE study.

Besides the impact of disease per se, the use of immunomodulatory therapies in adolescents with relapsing-remitting multiple sclerosis (RRMS) may have an effect on quality of life (QL). The FUTURE (Quality of liFe in adolescent sUbjecTs affected by mUltiple sclerosis treated with immunomodulatoRy agEnt using self-injecting device) study was designed to evaluate the changes in QL of Italian adolescents with RRMS receiving treatment with IFN-ß1a (Rebif; 22 µg), administered subcutaneously three times weekly using the RebiSmart™ electronic autoinjection device over a 52-week period. Fifty adolescents with RRMS were enrolled and 40 completed the study. Changes from baseline to end of treatment (EoT) in adolescent self-reported and parent-reported QL were assessed using the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL), which has been validated for use in pediatric MS and for which an Italian version is available. The adolescent self-reported total PedsQL4.0 score and all of its subscales tended to increase from baseline to EoT, the only exception being "Emotional functioning." In parent-reported measures, the total PedsQL4.0 score increased significantly from baseline to EoT (+ 5.27 points, p = 0.041). Significant increases were also evident for parent-reported "Psychosocial health summary score" (+ 5.90 points; p = 0.015) and "School functioning" (+ 7.84 points; p = 0.029). Our results indicate that adolescents with RRMS using the electronic injection device RebiSmart™ for self-administration of Rebif® can experience long-term improvements in QL.

Striatal hand in Parkinson's disease: the re-evaluation of an old clinical sign.

Among postural abnormalities in Parkinson's disease (PD), striatal hand (SH) is a particularly underexplored phenomenon. It leads to extreme abnormalities of hand posture, causing altered dexterity, pain and disfigurement. In our study, three blinded investigators examined several pictures of the hands of individuals with PD (N = 40) and controls (N = 15). The investigators quantified postural alterations using the Striatal Hand Score. Demographic and clinical data were also collected. As no differences were detected among investigators agreement, a final Hand Score (HS, range 0-4) was obtained for each hand. The Striatal Hand Score in both the left and right hand was significantly different in PD compared to controls (p < 0.001 for both left and right hand). Striatal hand was significantly worse on the side of PD onset, and on the side with greater PD symptomatology. The finding of a striatal hand was 100 % specific for a diagnosis of PD. Nine PD subjects were evaluated both on and off medication, and dopaminergic treatment did not significantly change the Striatal Hand Score. Our findings suggest that in patients without any explanation for hand deformities other than PD, striatal hand occurs very often, and is highly specific for the side of worst PD involvement. We recommend including an evaluation for SH as part of routine practice. This study emphasizes the importance of a careful observation of the patient in order to improve diagnostic accuracy.

Narrow band imaging with magnification endoscopy for celiac disease: results from a prospective, single-center study.

In celiac disease (CD), the intestinal lesions can be patchy and partial villous atrophy may elude detection at standard endoscopy (SE). Narrow Band Imaging (NBI) system in combination with a magnifying endoscope (ME) is a simple tool able to obtain targeted biopsy specimens. The aim of the study was to assess the correlation between NBI-ME and histology in CD diagnosis and to compare diagnostic accuracy between NBI-ME and SE in detecting villous abnormalities in CD. Forty-four consecutive patients with suspected CD undergoing upper gastrointestinal endoscopy have been prospectively evaluated. Utilizing both SE and NBI-ME, observed surface patterns were compared with histological results obtained from biopsy specimens using the k-Cohen agreement coefficient. NBI-ME identified partial villous atrophy in 12 patients in whom SE was normal, with sensitivity, specificity, and accuracy of 100%, 92.6%, and 95%, respectively. The overall agreement between NBI-ME and histology was significantly higher when compared with SE and histology (kappa score: 0.90 versus 0.46; P = 0.001) in diagnosing CD. NBI-ME could help identify partial mucosal atrophy in the routine endoscopic practice, potentially reducing the need for blind biopsies. NBI-ME was superior to SE and can reliably predict in vivo the villous changes of CD.

Prospective multicenter randomized trial comparing banding ligation with sclerotherapy of esophageal varices.

BACKGROUND/AIMS: Endoscopic variceal banding ligation (EVL), first described by Stiegmann in 1988, is now an accepted alternative to sclerotherapy (EVS) for esophageal varices with previous bleeding. However, results are conflicting in terms of complications, eradication, recurrence, rebleeding and mortality rate. We aimed to compare EVL with EVS in a prospective randomized trial in patients with previous esophageal bleeding proved by endoscopy. End points were rebleeding rate and death during a short (eradication period) or long-term follow-up (> 1 year). METHODOLOGY: One hundred patients (50 EVL, 50 EVS) were enrolled. Eradication rate, number of treatments needed to achieve eradication, recurrence of varices, rebleeding and complications were recorded and analyzed. RESULTS: No differences were observed between the two groups regarding age, sex and Child class. One patient dropped out in the EVL group and 6 in the EVS group. Eradication was obtained in 44 (88%) with EVL and 41 (82%) with EVS with a mean of 3.41 and 5.29 treatments (p<0.001), respectively. Rebleeding occurred during eradication in 6 patients (12%) in the EVL group and 21 (42%) in the EVS group (p=0.001); after eradication, 7 patients (14%) rebled in the EVL group and 4 (8%) in the EVS group (not significant). Non-variceal bleeding was observed in 5 patients (2 EVL and 3 EVS) during follow-up. Two patients in the EVL group died after variceal rebleeding; 3 died of gastric bleeding; and, 15 from non-hemorrhagic events (8 EVL and 7 EVS). In the EVL group 14 patients had recurrent varices and 7 rebled; in the EVS group 11 recurred, with rebleeding in 5. Major complications were fewer in the EVL group (1 stenosis, 4 chronic ulcers) compared to 18 patients in the EVS group (9 stenosis and 9 chronic ulcers) (p<0.005). CONCLUSIONS: EVL might be preferable to EVS for faster reduction and obliteration of varices, with a lower rate of complications and rebleeding before eradication. No differences were observed in recurrence.

Effects of early ductal decompression in human biliary acute pancreatitis.

It was recently demonstrated in experimental models that, after pancreatic outflow obstruction, serum amylase levels first increase and then progressively decline regardless of whether the obstruction was maintained or relieved. Furthermore, early decompression of the ductal biliary system may prevent the progression of the disease. This finding prompted us to look for a similar pattern in patients with obstructive acute pancreatitis due to biliary stones. Forty-two patients with biliary acute pancreatitis were prospectively studied. Twenty-one patients underwent urgent endoscopic sphincterotomy (ES), and 21 received conservative medical treatment (CMT). The two groups were comparable for sex, age, onset of pain, and severity. Serum amylase and lipase were determined in all patients on admission and 24 h later. The percentage variation of serum amylase and lipase was calculated considering, for each patient, the concentrations of the two enzymes assayed on admission and 24 h later. On admission, all patients had elevated serum concentrations of amylase (mean +/- SEM: ES, 2,560+/-473 U/L; CMT, 1,783+/-481 U/L) and lipase (ES, 3,037+/-574 U/L; CMT, 3,179+/-724 U/L). The serum amylase variation (mean +/- SEM) was -65.6+/-5.5% in the ES and -47.2.1+/-8.1% in the CMT patients. The serum lipase variation was -59.1+/-7.7 and -33.1+/-18% in the same groups, respectively. These differences were not statistically significant. Acute pancreatitis worsened in one patient in the ES group and in seven in the CMT group; this difference was statistically significant (p < 0.02). The mean length of hospitalization was 8.9 days in the ES group and 19.7 days in the CMT group (p < 0.001). Serum pancreatic enzymes determination is not useful to evaluate the results of the early decompression of biliary duct in human acute pancreatitis. Indeed, early endoscopic sphincterotomy may result in a substantial improvement in the outcome of biliary acute pancreatitis.

A prospective randomized trial of sclerotherapy versus ligation in the elective treatment of bleeding esophageal varices.

BACKGROUND AND STUDY AIMS: Endoscopic ligation (EVL) and endoscopic variceal sclerotherapy (EVS) are known to be equally effective in eradicating bleeding esophageal varices in patients with hepatic cirrhosis, but the long-term safety and efficacy of the two techniques have not been clearly established. The aim of this study was to determine the relative frequency of rebleeding, recurrence of varices, and survival after treatment with the two techniques during a relatively long follow-up period. PATIENTS AND METHODS: A total of 111 patients without bleeding at the index endoscopy were randomly assigned to either EVL (n = 57) or EVS (n = 54). After eradication of the varices, the patients received endoscopic examinations every three months and for each episode of rebleeding. RESULTS: The mean follow-up periods were 534 +/- 42 days in the EVS group and 496 +/- 40 days in the EVL group. The two techniques were equally effective in eradicating varices (93% in EVL group and 92.5% in EVS group). The mean number of sessions required to obtain eradication was slightly lower (mean +/- SE) in the EVL group (3.5 +/- 0.1 vs. 4.0 +/- 0.1, P = 0.004), while the time required for eradication was longer (33.8 +/- 2.1 vs. 27.3 +/- 1.4, P = 0.01). The comparison of the Kaplan-Meier estimates of survival and time to first rebleeding did not show any statistically significant differences between the two groups. The rate of complications was significantly higher in the EVS group than in the EVL group (31% vs. 11%, P = 0.001), while the rate of recurrent varices during follow-up was higher in the EVL group (30% vs. 13%, P = 0.03). CONCLUSIONS: While the two techniques are equally effective, ligation treatment shows greater advantages in the short-term follow-up, but is associated with more frequent recurrence of varices in the longer term. These two aspects should be considered for evaluation in the cost-benefit ratio and quality of life analysis. All patients should have frequent endoscopic evaluations (every three or four months) throughout the first year of follow-up.

[Oral pefloxacin in the treatment of acute gastroenteritis]. / La pefloxacina per os nel trattamento delle gastroenteriti acute.

UNLABELLED: In the case of travellers' diarrhoea, in order to reduce to a minimum the period of sickness and temporary invalidity, suitable therapy needs to be undertaken, involving the reintegration of fluids and electrolytes, as well as antibiotic treatment whose spectrum of action covers the most commonly isolated microorganisms. The aim of the study was to verify the rapidity of the antibacterial action of pefloxacin in the treatment of this type of gastrointestinal infection. MATERIALS AND METHODS: The patients enrolled were treated for 5 days with pefloxacin in tablets containing 400 mg of the active agent, given orally. Treatment involved a first dose of 800 mg (2 tablets in a single administration), followed by 400 mg twice a day (1 tablet every 12 hours). Administration was carried out prevalently at mealtimes. At the end of treatment a two-week follow-up period was scheduled. At the beginning of the study, and after 5 days' treatment, a coproculture was carried out, with identification of the germ responsible for the infection. The study was carried out in accordance with the principles of the Helsinki declaration and its revisions, in particular each patient gave his/her informed consent to participate in the trial. RESULTS: Thirty patients enrolled in the study (16 males, 14 females), of mean age 48.2 years (18-82 min-max), mean weight of 66.3 kg (46-88 min-max), suffering from acute gastroenteritis. The coproculture carried out at the baseline for all patients led to the isolation in 10 patients, of 10 pefloxacin-sensitive GRAM-negative bacterial strains: Salmonella spp. in 6 cases, Shigella spp. in 2, Escherichia coli in 1 and Yersinia enterocolitica in 1. At the end of treatment and follow-up the coproculture indicated that all the germs isolated initially had been eradicated and no cases of superinfection or reinfection occurred. The number of daily evacuations gradually decreased from a mean of 6.8 at the baseline to 1.1 on the fifth day (p<0.0001). The consistency of faeces had increased in a significant fashion by the third day and at the end of treatment 93.3% of patients had well-formed faeces. In the course of treatment abdominal pain, nausea and vomiting decreased progressively and body temperature returned within normal limits by the third day. Safety was excellent in 93.3% of patients, with one case of nausea and one of erythema, which resolved spontaneously in the course of treatment. At the end of treatment with pefloxacin, the physician expressed his final judgment of efficacy, which was excellent in 86.7% of cases (26/30) and good in 13.3% (4/30), in accordance with the clinical evaluation of recovery in 93.3% of cases (28/30) and of improvement in 6.7% (2/30). CONCLUSIONS: In forms of acute gastroenteritis in which coproculture shows the presence of germs sensitive to pefloxacin, the use of this quinolone guarantees a high percentage of success with a short course of treatment.

Evaluation of undiluted N-butyl-2-cyanoacrylate in the endoscopic treatment of upper gastrointestinal tract varices.

BACKGROUND AND STUDY AIMS: Endoscopic obliteration of upper gastrointestinal tract varices using N-butyl-2-cyanoacrylate has been proposed by some authors. The aim of the present study was to evaluate prospectively the efficacy and safety of this technique, using the undiluted substance, in obtaining hemostasis of bleeding upper gastrointestinal tract varices, as well as definitive eradication of varices located in the gastric fundus and duodenum. PATIENTS AND METHODS: We carried out variceal injections of N-butyl-2-cyanoacrylate in 80 patients (51 males, 29 females, mean age 68 years, range 19-80) with upper gastrointestinal tract varices. In 24 patients, the varices were located in the esophagus, in 54 in the gastric fundus, and in the remaining two they were in the duodenum. Forty-eight patients were treated for active variceal bleeding, and the other 32 were treated electively. RESULTS: Hemostasis was achieved in 43 of the 48 patients (89.6%) treated for active variceal bleeding. Eradication was obtained in 49 of the 56 patients (87.5%) with gastric or duodenal varices. Overall complications occurred in 11 patients (10.4%). In two patients, embolization was found, and in a further two patients it was clinically suspected, but could not be proved. Ten patients (12.5%) died during the treatment period, six due to uncontrolled bleeding, two due to rebleeding, and two due to liver failure. CONCLUSIONS: Endoscopic injection of N-butyl-2-cyanoacrylate appears to be both safe and effective in the treatment of bleeding gastrointestinal tract varices. The relative value of the undiluted substance versus the diluted one should be further evaluated.

Role of esophageal brushing cytology in monitoring patients treated with sclerotherapy for esophageal varices.

Recent reports claim that there might be a relationship between sclerotherapy for esophageal varices and cancer of the esophagus. The discovery of a squamous cell cancer of the lower esophagus in a patient treated three years previously with sclerotherapy led us to set up a follow-up protocol. In order to assess this relationship and to monitor the evolution of such lesions, 68 patients treated with sclerotherapy with polidocanol because of esophageal varices were examined endoscopically at six-month intervals, and brushing samples were taken. The ages of the patients ranged between 35 and 81 years, and all had portal hypertension due to cirrhosis; 10 patients with the same disease but without bleeding varices were also examined. The interval between sclerotherapy and the first cytologic follow-up examination averaged 34 months, while the interval to the last follow-up examination averaged 40 months. One patient was examined four times (1.4%), 10 three times (14.7%), 39 twice (57.4%) and 18 only once (26.5%). Two cases were interpreted as nuclear hyperplasia associated with inflammation and were found to have regressed at a subsequent examination; all the other cases were reported as negative although sometimes associated with inflammation. None of the controls showed any abnormalities. While the occurrence of esophageal cancer after sclerotherapy might be associated with other risk factors, such as alcohol intake and smoking, esophageal brushing cytology can successfully monitor these patients and detect early stages of neoplasia.