Nabilone as an adjunctive to gabapentin for multiple sclerosis-induced neuropathic pain: a randomized controlled trial.

BACKGROUND: Neuropathic pain (NPP) is a chronic syndrome suffered by patients with multiple sclerosis (MS), for which there is no cure. Underlying cellular mechanisms involved in its pathogenesis are multifaceted, presenting significant challenges in its management. METHODS: A randomized, double-blind, placebo-controlled study involving 15 relapsing-remitting MS patients with MS-induced NPP was conducted to evaluate nabilone combined with gabapentin (GBP). Eligible patients stabilized on GBP (≥1,800 mg/day) with inadequate pain relief were recruited. Nabilone or placebo was titrated over 4 weeks (0.5 mg/week increase) followed by 5-week maintenance of 1 mg oral nabilone (placebo) twice daily. Primary outcomes included two daily patient-reported measures using a 100-mm visual analog scale (VAS), pain intensity (VASpain), and impact of pain on daily activities (VASimpact). Hierarchical regression modeling was conducted on each outcome to determine if within-person pain trajectory differed across study groups, during 63-day follow-up. RESULTS: After adjustment for key patient-level covariates (e.g., age, sex, Expanded Disability Status Scale, duration of MS, baseline pain), a significant group × time(2) interaction term was reported for both the VASpain (P < 0.01) and VASimpact score (P < 0.01), demonstrating the adjusted rate of decrease for both outcomes was statistically greater in nabilone vs placebo study group. No significant difference in attrition rates was noted between treatments. Nabilone was well tolerated, with dizziness/drowsiness most frequently reported. CONCLUSION: Nabilone as an adjunctive to GBP is an effective, well-tolerated combination for MS-induced NPP. The results of this study identify a novel therapeutic combination for use in this population of patients predisposed to tolerability issues that may otherwise prevent effective pain management.

Second primary common bile duct neuroendocrine tumor after 10 years in a patient with rectal adenocarcinoma: A case report.

Background: With the improvement of cancer treatment methods and increased life expectancy of patients, the prevalence of second primary cancers has gradually increased. Case Presentation: In the present study, the case was a 58-year-old man diagnosed with rectal adenocarcinoma and underwent chemotherapy and neoadjuvant radiotherapy 10 years ago. After 5 years, he underwent a lobectomy due to lung metastasis. At the research time, he presented with itching; in ERCP, a 16-millimeter hypoechoic lesion was detected, and an FNA biopsy was performed, indicating malignancy. The patient underwent Whipple surgery, and pathology revealed a well-differentiated neuroendocrine tumor. He was discharged in good general condition. Conclusion: This article emphasized the necessity of early detection and diagnosis of second primary cancer, as well as acting as if it was primary cancer to treat.

Physical properties of food or bile redirection do not contribute to the intestinal adaptations after Roux-en-Y Gastric Bypass in rats.

Objective: Metabolic and morphological adaptations of the intestine have been suggested to play a role in the various therapeutic benefits of Roux-en-Y Gastric Bypass (RYGB) surgery. However, the precise underlying mechanisms remain unclear. In this study, the effects of physical properties of ingested food and redirection of biliopancreatic secretions on intestinal remodeling were investigated in RYGB operated rats. Methods: RYGB employing two different Roux Limb (RL) lengths was performed on high fat diet induced obese rats. Post-operatively, rats were fed either Solid or isocaloric Liquid diets. Metabolic and morphological remodeling of intestine was compared across both diet forms (Solid and Liquid diets) and surgical models (Short RL and Long RL). Results: RYGB surgery in rats induced weight loss and improved glucose tolerance which was independent of physical properties of ingested food and biliopancreatic secretions. Intestinal glucose utilization after RYGB was not determined by either food form or biliopancreatic secretions. The GLUT-1 expression in RL was not influenced by physical properties of food. Furthermore, both physical properties of food and biliopancreatic secretions showed no effects on intestinal morphological adaptations after RYGB. Conclusion: Results of this study demonstrate that physical properties of food and bile redirection are not major determinants of intestinal remodeling after RYGB in rats.

Mechanoscopy: A Novel Device and Procedure for in vivo Detection of Chronic Colitis in Mice.

BACKGROUND: Gut stiffening caused by fibrosis plays a critical role in the progression of inflammatory bowel disease (IBD) and colon cancer. Previous studies have characterized the biomechanical response of healthy and pathological gut, with most measurements obtained ex vivo. METHODS: Here, we developed a device and accompanying procedure for in vivo quantification of gut stiffness, termed mechanoscopy. Mechanoscopy includes a flexible balloon catheter, pressure sensor, syringe pump, and control system. The control system activates the balloon catheter and performs automated measurements of the gut stress-strain biomechanical response. RESULTS: A gut stiffness index (GSI) is identified based on the slope of the obtained stress-strain response. Using a colitis mouse model, we demonstrated that GSI positively correlates with the extent of gut fibrosis, the severity of mucosal damage, and the infiltration of immune cells. Furthermore, a critical strain value is suggested, and GSI efficiently detects pathological gut fibrotic stiffening when the strain exceeds this value. CONCLUSIONS: Based on these results, we envision that mechanoscopy and GSI will facilitate the clinical diagnosis of IBD.

Here, we present a novel procedure/device, termed mechanoscopy, which we have demonstrated to accurately detect and differentiate between fibrosis and inflammation in rodent models of colitis. Thus, mechanoscopy offers a translationally relevant approach for ultrasensitive and minimally invasive IBD diagnosis.

Staphylococcus aureus harbouring Enterotoxin A as a possible risk factor for multiple sclerosis exacerbations.

BACKGROUND: Staphylococcus aureus may produce superantigens that can non-specifically activate CD4(+) cells to potentially target the myelin basic protein. OBJECTIVE: This study examined the association between individuals with multiple sclerosis (MS) and colonization with S. aureus harbouring superantigens. METHODS: Nasal swabs were collected from non-MS subjects and patients with MS who had not experienced a relapse in the past six months (MS stable group) and who had suffered a relapse within 30 days of study recruitment (MS exacerbation group). S. aureus was isolated from the anterior nares of participants following standard procedures and staphylococcal superantigen genes (sea, seb, and tsst-1) were detected using standard laboratory PCR techniques. RESULTS: The study enrolled 204 patients, 80 in the non-MS and MS stable groups and 44 patients in the MS exacerbation group. Overall, 27.0% of patients were colonized with S. aureus with no significant differences identified between study groups. Amongst individuals colonized with S. aureus, the prevalence of sea was significantly greater in the MS exacerbation versus non-MS study group (p < 0.05; odds ratio 7.9; 95% confidence interval 1.2-49.5). CONCLUSIONS: The ability to rapidly screen patients for the presence of S. aureus producing sea may serve as a useful marker of a potential MS exacerbation.

Effective Factors on the Disappearance of Residual Cavity Following Conservative Surgery of Liver Hydatid Cysts.

BACKGROUND: Surgery is one of the treatments commonly used to treat liver hydatid cyst. Remaining of the residual cavity after conservative surgery may lead to some harmful complications. In this study, we evaluated the role of different factors affecting the disappearance of the residual cyst. MATERIALS AND METHODS: Seventy-five patients were evaluated in 2.5 years. Patients were divided into two groups based on the remaining or disappearance of the residual cavity in follow-up visits. The baseline demographic features, preoperative cysts' size, type of technique used to eliminate the residual cavity, and cavity wall characteristics were compared in the two groups. RESULTS: Residual cavity was disappeared in 46 (61%) patients after 2 years. Calcification of the wall and wall stiffness were more common in patients with the remained residual cavity (89.6% vs. 8.7% [P < 0.001] and 58.6% vs. 30.4% [P < 0.01], respectively). Demographic features, preoperative cysts' characteristics, and the procedure used during surgery were not statistically different between groups. CONCLUSIONS: Cyst wall calcification and wall stiffness had a role in predicting residual cavity disappearance. These factors can help surgeons to predict patients at higher risk of posthydatid cyst resection residual cavity.

Fatigue and cognition in patients with relapsing multiple sclerosis treated with interferon ß.

INTRODUCTION: Fatigue and cognitive deficits are common symptoms affecting patients with multiple sclerosis. METHODS: The effects of interferon beta on fatigue and cognitive deficits were assessed in 50 patients with relapsing multiple sclerosis (recruited at a single center). The pre-treatment assessments were performed on visits 1 and 2 (Months 0 and 3). Patients started treatment with subcutaneous interferon beta-1a or beta-1b, or intramuscular interferon beta-1a at Month 3, with reassessment at visits 3 and 4 (6 and 12 months, respectively). Co-primary endpoints were change in fatigue (Modified Fatigue Impact Scale) and change in cognition (Brief Repeatable Battery of Neuropsychological Tests) from pre-treatment to visits 3 and 4. Follow-up data were obtained for 40 patients. RESULTS: The pre-treatment demographic and disease characteristics did not differ between groups. Improvements in fatigue levels were reported for patients receiving subcutaneous interferon beta-1a versus patients in the intramuscular interferon beta-1a group (p = .04) and in the interferon beta-1b group (p = .09). Improvements were also reported in five out of 17 cognitive indices for all the treatment groups. CONCLUSION: The data suggest that interferon beta may reduce fatigue and cognitive deficits in patients with relapsing multiple sclerosis. Larger, randomized, and controlled studies are required to confirm our findings.

The effect of Punica granatum L. flower extract on post-surgical peritoneal adhesions in a rat model.

OBJECTIVE: Peritoneal adhesions may develop after every abdominopelvic surgery. Many agents and technical modifications have been investigated to minimize adhesions. Punica granatum (pomegranate) flower has some anti-inflammatory and antioxidative effects that would reduce the formation of peritoneal adhesions. In the present study, the effects of different doses of oral Punica granatum flower extract on postoperative peritoneal adhesions were evaluated in a rat model. STUDY DESIGN: Thirty-two female Wistar rats were divided into four groups: one control group (CG) and three experimental groups, treated with 100 (EG100), 200 (EG200), and 400 (EG400) mg/kg/day Punica granatum extract orally for eight days. Induction of peritoneal adhesions was done in all groups using the same method. Two weeks after the first surgery, all rats re-operated and adhesions were evaluated via both macroscopic and microscopic changes. RESULTS: We observed that rats in the control group had statistically higher adhesion area and more severe adhesions when compared to all experimental groups. Besides, those in the EG-400 group had a significantly lower rate of foreign body reaction in serosal layer when compared to the other three study groups. Other microscopic findings were comparable between the four groups. CONCLUSION: Administration of the oral Punica granatum flower extract was associated with a decreased quantity and quality of the adhesions in the animal model of rat in this study. This therapy might be an effective and safe strategy to reduce intraperitoneal adhesion after abdominal surgeries in animal models.

A treatment algorithm for neuropathic pain: an update.

OBJECTIVE: The purpose of this review is to provide an update of the neuropathic pain treatment algorithm previously published by Namaka et al. in 2004. This algorithm focuses on the strategic incorporation of the latest pain therapies while providing an update of any recent developments involving medications previously listed in the algorithm. DATA SOURCES: PubMed, MEDLINE, Cochrane, and Toxnet databases were used to conduct all literature searches on neuropathic pain and targeted treatment strategies. Comprehensive search efforts in the identified databases included studies published between 1980 and 2009. The search term "neuropathic pain" was used along with each of the agents outlined in this review: pregabalin, paroxetine CR, duloxetine, tramadol XL, Tramacet, Sativex, and nabilone. STUDY SELECTION: A total of 90 studies were reviewed and selected based on level 1, 2, and 3 search strategies. DATA EXTRACTION: Level 1 search strategies were initially aimed at evidence-based trials of large sample size (N > 100), with a randomized, double-blind, placebo-controlled design conducted by investigators well versed in the specialty area of interest. A level 2 search was conducted for additional trials that had many, but not all, of the desirable traits of evidence-based trials. In addition, a level 3 search strategy was conducted to compare key findings stated in anecdotal reports of very small (N < 15), poorly designed trials with the results of well-designed, evidence-based trials identified in level 1 and/or level 2 searches. DATA SYNTHESIS: Based on a thorough evaluation of the literature, pregabalin, paroxetine CR, and duloxetine have been placed in the updated algorithm as first-line agents, while tramadol XL, Tramacet, Sativex, and nabilone function primarily as adjunctive agents. CONCLUSION: The updated algorithm provides a baseline framework from which clinicians can justify the medication they prescribe.

Comparison of the Bile Reflux Frequency in One Anastomosis Gastric Bypass and Roux-en-Y Gastric Bypass: a Cohort Study.

INTRODUCTION: One of the most acceptable procedures in bariatric surgery is laparoscopic gastric bypass. Laparoscopic Roux-en-Y gastric bypass (RYGB) is a common technique used in bariatric surgery. Recently, one anastomosis gastric bypass (OAGB) has been suggested as a simple, fast, and effective technique for obesity treatment. This study aims to compare the frequency of histologically proven bile reflux in OAGB and RYGB among patients with morbid obesity. METHODS: This prospective cohort study was performed from 2015 to 2017 in the Department of Bariatric Surgery of Isfahan University of Medical Sciences, Isfahan, Iran. Patients who had undergone RYGB or OAGB surgery were enrolled. Patients who had undergone revisional surgery were excluded. Data on demographics, symptoms, fasting blood sugar, lipid profile, endoscopic, and histologic findings (based on the Sydney bile reflux index) of bile reflux and postoperative complications were collected and compared for the two techniques. RESULTS: A total of 122 obese patients (22 males) who had undergone RYGB or OAGB surgery were included. The Sydney bile reflux index showed no statistically significant difference between RYGB and OAGB groups. Similarly, no statistically significant difference was found in the self-reported history of bile reflux-related symptoms, bile reflux markers in esophagogastroduodenoscopy, and postoperative complications between groups. CONCLUSIONS: OAGB and RYGB appear to be equal with respect to postoperative complications, bile reflux frequency, bile reflux index, and the Sydney system score.

Examining the roles of cannabinoids in pain and other therapeutic indications: a review.

IMPORTANCE OF THE FIELD: In recent times, our knowledge of cannabinoids and the endocannabinoid system has greatly advanced. With expanding knowledge, synthetic cannabinoids - including nabilone, dronabinol and a combination of synthetic Delta9-THC and cannabidiol - have been developed and tested for benefit in a variety of therapeutic indications. AREAS COVERED IN THIS REVIEW: The aim of this article is to provide a summative review of the vast amount of clinical trial data now available on these agents. WHAT THE READER WILL GAIN: To locate clinical trials for review, a literature search was performed using PubMed between the dates of 25 May and 30 June 2009. Search parameters were set to isolate only human randomized controlled trials (RCTs) published between 1990 and 2009. Keywords consistently used for each search include: cannabinoids, marijuana, THC, nabilone and dronabinol. Preferential selection was given to the best-designed trials, focusing on placebo-controlled, double-blind RCTs with the largest patient populations, if available. TAKE HOME MESSAGE: As efficacy and tolerability of these agents remain questionable, it is important that cannabinoids not be considered 'first-line' therapies for conditions for which there are more supported and better-tolerated agents. Instead, these agents could be considered in a situation of treatment failure with standard therapies or as adjunctive agents where appropriate.