Underwater Endoscopic Mucosal Resection Vs Conventional Endoscopic Mucosal Resection for Superficial Nonampullary Duodenal Epithelial Tumors in the Western Setting.

BACKGROUND & AIMS: Conventional endoscopic mucosal resection (C-EMR) is established as the primary treatment modality for superficial nonampullary duodenal epithelial tumors (SNADETs), but recently underwater endoscopic mucosal resection (U-EMR) has emerged as a potential alternative. The majority of previous studies focused on Asian populations and small lesions (≤20 mm). We aimed to compare the efficacy and outcomes of U-EMR vs C-EMR for SNADETs in a Western setting. METHODS: This was a retrospective multinational study from 10 European centers that performed both C-EMR and U-EMR between January 2013 and July 2023. The main outcomes were the technical success, procedure-related adverse events (AEs), and the residual/recurrent adenoma (RRA) rate, evaluated on a per-lesion basis. We assessed the association between the type of endoscopic mucosal resection and the occurrence of AEs or RRAs using mixed-effects logistic regression models (propensity scores). Sensitivity analyses were performed for lesions ≤20 mm or >20 mm. RESULTS: A total of 290 SNADETs submitted to endoscopic resection during the study period met the inclusion criteria and were analyzed (C-EMR: n = 201, 69.3%; U-EMR: n = 89, 30.7%). The overall technical success rate was 95.5% and comparable between groups. In logistic regression models, compared with U-EMR, C-EMR was associated with a significantly higher frequency of overall delayed AEs (odds ratio [OR], 4.95; 95% CI, 2.87-8.53), postprocedural bleeding (OR, 7.92; 95% CI, 3.95-15.89), and RRAs (OR, 3.66; 95% CI, 2.49-5.37). Sensitivity analyses confirmed these results when solely considering either small (≤20 mm) or large (>20 mm) lesions. CONCLUSIONS: Compared with C-EMR, U-EMR was associated with a lower rate of overall AEs and RRAs, regardless of lesion size. Our results confirm the possible role of U-EMR as an effective and safe technique in the management of SNADETs.

Multisegmented esophageal fully covered self-expandable metal stent for palliation of malignant dysphagia: a prospective, multicenter feasibility and safety study.

BACKGROUND AND AIMS: A novel multisegmented esophageal fully covered self-expandable metal stent (FCSEMS) was designed to reduce stent migration, which is seen in up to 30% of patients. The goal of this study was to evaluate the safety and efficacy of the multisegmented FCSEMS. METHODS: This multicenter prospective study aimed to include 30 patients undergoing palliative stent placement. Efficacy, defined as technically successful stent placement and dysphagia scores, and safety, defined as the number of adverse events (AEs) and serious AEs (SAEs), were measured. RESULTS: The study was prematurely terminated due to safety concerns after including 23 patients (mean ± standard deviation age, 72 ± 10 years; 78% male). Stent placement was technically successful in 21 patients (91%), and dysphagia scores had improved in all patients with successful stent placement. SAEs were reported in 16 (70%) patients. Stent-related mortality occurred in 3 patients (13%). CONCLUSIONS: The multisegmented FCSEMS successfully treated malignant dysphagia. The study was prematurely terminated, however, because stent placement was associated with a relatively high SAE rate. (Clinical trial registration number: NCT04415463.).

Best Practices in Pancreatico-biliary Stenting and EUS-guided Drainage.

Indications for endoscopic placement of endoluminal and transluminal stents have greatly expanded over time. Endoscopic stent placement is now a well-established approach for the treatment of benign and malignant biliary and pancreatic diseases (ie, obstructive jaundice, intra-abdominal fluid collections, chronic pancreatitis etc.). Ongoing refinement of technical approaches and development of novel stents is increasing the applicability and success of pancreatico-biliary stenting. In this review, we discuss the important developments in the field of pancreatico-biliary stenting, with a specific focus on endoscopic retrograde cholangiopancreatography and endoscopic ultrasound-associated developments.

Barriers and facilitators for safe sex behaviors in students from universidad de Santiago de Chile (USACH) through the COM-B model.

BACKGROUND: Unsafe sex is one of the main morbidity and mortality risk factors associated with sexually transmitted infections (STIs) in young people. Behavioral change interventions for promoting safe sex have lacked specificity and theoretical elements about behavior in their designs, which may have affected the outcomes for HIV/AIDS and STI prevention, as well as for safe sex promotion. This study offers an analysis of the barriers and facilitators that, according to the university students who participated in the focus groups, impede or promote the success of interventions promoting healthy sexuality from the perspective of the actions stakeholders should undertake. In turn, this study proposes intervention hypotheses based on the Behavior Change Wheel which appears as a useful strategy for the design of intervention campaigns. METHODS: Two focus groups were organized with students from Universidad de Santiago de Chile (USACH). The focus groups gathered information about the perceptions of students about sex education and health, risk behaviors in youth sexuality, and rating of HIV/AIDS and STI prevention campaigns. In the focus groups, participants were offered the possibility of presenting solutions for the main problems and limitations detected. After identifying the emerging categories related to each dimension, a COM-B analysis was performed, identifying both the barriers and facilitators of safe sex behaviors that may help orient future interventions. RESULTS: Two focus groups were organized, which comprised 20 participants with different sexual orientations. After transcription of the dialogues, a qualitative analysis was performed based on three axes: perception about sex education, risk behaviors, and evaluation of HIV/AIDS and STI prevention campaigns. These axes were classified into two groups: barriers or facilitators for safe and healthy sexuality. Finally, based on the Behavior Change Wheel and specifically on its 'intervention functions', the barriers and facilitators were integrated into a series of actions to be taken by those responsible for promotion campaigns at Universidad de Santiago. The most prevalent intervention functions are: education (to increase the understanding and self-regulation of the behavior); persuasion (to influence emotional aspects to promote changes) and training (to facilitate the acquisition of skills). These functions indicate that specific actions are necessary for these dimensions to increase the success of promotional campaigns for healthy and safe sexuality. CONCLUSIONS: The content analysis of the focus groups was based on the intervention functions of the Behavior Change Wheel. Specifically, the identification by students of barriers and facilitators for the design of strategies for promoting healthy sexuality is a useful tool, which when complemented with other analyses, may contribute improving the design and implementation of healthy sexuality campaigns among university students.

The importance of inflammatory biomarkers in non-specific acute and chronic low back pain: a systematic review.

OBJECTIVE: The purpose of this study was to systematically review the evidence on inflammatory biomarkers as analytic predictors of non-specific low back pain (NsLBP). Low back pain (LBP) is the number one cause of disability globally, posing a major health problem that causes an enormous social and economic burden, and there is an increasing interest on the importance of biomarkers in quantifying and even emerge as potential therapeutic tools to LBP. METHODS: A systematic search was conducted on July 2022 in Cochrane Library, MEDLINE and Web of Science for all the available literature. Cross-sectional, longitudinal cohort or case-control studies that evaluated the relationship between inflammatory biomarkers collected from blood samples and low back pain in humans were considered eligible for inclusion, as well as prospective and retrospective studies. RESULTS: The systematic database search resulted in a total of 4016 records, of which 15 articles were included for synthesis. Sample size comprised a total of 14,555 patients with LBP (acute LBP (n = 2073); chronic LBP (n = 12482)) and 494 controls. Most studies found a positive correlation between classic pro-inflammatory biomarkers and NsLBP, namely C-reactive protein (CRP), interleukin 1 (IL-1) and IL-1ß, interleukin 6 (IL-6) and tumour necrosis factor α (TNF-α). On the other hand, anti-inflammatory biomarker interleukin 10 (IL-10) demonstrated a negative association with NsLBP. Four studies have made direct comparisons between ALBP and CLBP groups regarding their inflammatory biomarkers profile. CONCLUSIONS: This systematic review found evidence of increased levels of pro-inflammatory biomarkers CRP, IL-6 and TNF-α and decreased levels of anti-inflammatory biomarker IL-10 in patients with LBP. Hs-CRP was not correlated with LBP. There is insufficient evidence to associate these findings with the degree of pain severity or the activity status of the lumbar pain over time.

Clinical and Urodynamic results of the Argus T® sling in moderate and severe male stress urinary incontinence after radical prostatectomy - a 5 year prospective study.

PURPOSE: Sling as a therapeutic option for male stress urinary incontinence (SUI) has been reviewed in the last two decades, as it is a relatively simpliest surgery compared to artificial urinary sphincter and has the ability to modulate urethral compression. This study aims to evaluate the efficacy, rate of complications, quality of life and the effects on bladder emptying of the Argus T® compressive and ajustable sling in moderate and severe male SUI treatment. MATERIALS AND METHODS: Men eligible for stress urinary incontinence treatment after radical prostatectomy were recruited and prospectively evaluated, from March 2010 to November 2016. It was selected outpatient men with moderate and severe SUI, after 12 months of radical prostatectomy, who have failed conservative treatment. All patients had a complete clinical and urodynamic pre and post treatment evaluation, by means of clinical history, physical examination, urine culture, 1-hour pad test and ICIq-SF questionnaire. The UDS was performed after 12, 18 and 24 months postoperatively. RESULTS: Thirty-seven men underwent sling surgery, 19 patients (51.4%) with moderate and 18 (48.6%) with severe SUI. The minimum follow-up time was 5 years. Overall, we had a success rate of 56.7% at 60 months follow-up. After surgery, we did not observe significant changes in the urodynamic parameters evaluated during the follow-up. No patient had urodynamic bladder outlet obstruction (BOO) after sling implantation. Readjustment of the Argus T® sling was performed in 16 (41%) of the patients and 51% of the patients reported some adverse event. CONCLUSION: We demonstrate a long-term efficacy and safety of Sling Argus T® as an alternative to moderate and severe male SUI treatment. Furthermore, in our study bulbar urethra compression does not lead to bladder outlet obstruction.

Analysis of Reported Adverse Events With Colonic Stents: An FDA MAUDE Database Study.

BACKGROUND: Colonic stents are indicated for preoperative and palliative decompression of large bowel obstruction. We aim to investigate post Food and Drug Administration (FDA) approval outcomes associated with colonic stents. MATERIALS AND METHODS: We analyzed postmarketing surveillance data from the FDA Manufacturer and User Facility Device Experience (MAUDE) database from January 2011 to December 2020. RESULTS: During the study period, 691 device issues and 742 patient complications were identified. The number of adverse events reported to the FDA mildly increased from 6.40% in 2011 to 7.4% in 2020. Most device complications were due to a positioning problem (n=201, 29%), followed by device break (n=60, 8.6%), delamination (n=41, 6.3%), and migration or expulsion device (n=38, 5.55%). A number of reports described an unclassified adverse event without specifying device or operator problem (n=141, 20.3%). The most reported patient adverse events were perforation (n=150, 20.1%), death (n=47, 6.3%), abdominal pain/discomfort (n=27, 3.6%), and peritonitis (n=24, 3.2%). CONCLUSION: Findings from the MAUDE database highlight rare but important patient and device complications which endoscopists and referring providers should be aware of before consideration for colonic stent placement.

SARS-CoV-2 infection causes pulmonary shunt by vasodilatation.

Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may present a significant hypoxemia. The exactly mechanism of such hypoxemia in patients with coronavirus disease 2019 (COVID-19) is not well described. It has been suggested that microthrombosis contributes to this mechanism, increasing pulmonary dead space. However, dead spaces would not be sensible to oxygen supplementation, and also, enlargement of pulmonary vessels it has been evidenced. Shunt mechanism by vasodilatation, instead, could explain decubitus dependence in oxygenation by blood redistribution as observed in these patients, and moreover, would be more sensible to oxygen supplementation than dead spaces. We hypothesized that SARS-CoV-2 causes an intrapulmonary vascular dilatation (IPVD), determining a shunt mechanism by vasodilatation. We performed contrast-enhanced transthoracic echocardiography to search IPVD shunt in patients with confirmed COVID-19, hospitalized in an intensive care unit. Ten patients were recruited; one patient was excluded due to low quality of echocardiographic image, and nine patients were included. IPVD was found in seven (78%) patients, with different grades, including patient with normal compliance and the one without invasive ventilation. We demonstrated that shunt by IPVD is present among patients with COVID-19, and this mechanism is probably implicated in significant hypoxemia observed.

Retrospective multicenter study on endoscopic treatment of upper GI postsurgical leaks.

BACKGROUND AND AIMS: Therapeutic endoscopy plays a critical role in the management of upper GI (UGI) postsurgical leaks. Data are scarce regarding clinical success and safety. Our aim was to evaluate the effectiveness of endoscopic therapy for UGI postsurgical leaks and associated adverse events (AEs) and to identify factors associated with successful endoscopic therapy and AE occurrence. METHODS: This was a retrospective, multicenter, international study of all patients who underwent endoscopic therapy for UGI postsurgical leaks between 2014 and 2019. RESULTS: Two hundred six patients were included. Index surgery most often performed was sleeve gastrectomy (39.3%), followed by gastrectomy (23.8%) and esophagectomy (22.8%). The median time between index surgery and commencement of endoscopic therapy was 16 days. Endoscopic closure was achieved in 80.1% of patients after a median follow-up of 52 days (interquartile range, 33-81.3). Seven hundred seventy-five therapeutic endoscopies were performed. Multimodal therapy was needed in 40.8% of patients. The cumulative success of leak resolution reached a plateau between the third and fourth techniques (approximately 70%-80%); this was achieved after 125 days of endoscopic therapy. Smaller leak initial diameters, hospitalization in a general ward, hemodynamic stability, absence of respiratory failure, previous gastrectomy, fewer numbers of therapeutic endoscopies performed, shorter length of stay, and shorter times to leak closure were associated with better outcomes. Overall, 102 endoscopic therapy-related AEs occurred in 81 patients (39.3%), with most managed conservatively or endoscopically. Leak-related mortality rate was 12.4%. CONCLUSIONS: Multimodal therapeutic endoscopy, despite being time-consuming and requiring multiple procedures, allows leak closure in a significant proportion of patients with a low rate of severe AEs.

Esophageal stenting for benign and malignant disease: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2021.

MALIGNANT DISEASE: 1: ESGE recommends placement of partially or fully covered self-expandable metal stents (SEMSs) for palliation of malignant dysphagia over laser therapy, photodynamic therapy, and esophageal bypass.Strong recommendation, high quality evidence. 2 : ESGE recommends brachytherapy as a valid alternative, alone or in addition to stenting, in esophageal cancer patients with malignant dysphagia and expected longer life expectancy.Strong recommendation, high quality evidence. 3: ESGE recommends esophageal SEMS placement for sealing malignant tracheoesophageal or bronchoesophageal fistulas. Strong recommendation, low quality evidence. 4 : ESGE does not recommend SEMS placement as a bridge to surgery or before preoperative chemoradiotherapy because it is associated with a high incidence of adverse events. Other options such as feeding tube placement are preferable. Strong recommendation, low quality evidence. BENIGN DISEASE: 5: ESGE recommends against the use of SEMSs as first-line therapy for the management of benign esophageal strictures because of the potential for adverse events, the availability of alternative therapies, and their cost. Strong recommendation, low quality evidence. 6: ESGE suggests consideration of temporary placement of self-expandable stents for refractory benign esophageal strictures. Weak recommendation, moderate quality evidence. 7: ESGE suggests that fully covered SEMSs be preferred over partially covered SEMSs for the treatment of refractory benign esophageal strictures because of their very low risk of embedment and ease of removability. Weak recommendation, low quality evidence. 8: ESGE recommends the stent-in-stent technique to remove partially covered SEMSs that are embedded in the esophageal wall. Strong recommendation, low quality evidence. 9: ESGE recommends that temporary stent placement can be considered for the treatment of leaks, fistulas, and perforations. No specific type of stent can be recommended, and the duration of stenting should be individualized. Strong recommendation, low quality of evidence. 10 : ESGE recommends considering placement of a fully covered large-diameter SEMS for the treatment of esophageal variceal bleeding refractory to medical, endoscopic, and/or radiological therapy, or as initial therapy for patients with massive bleeding. Strong recommendation, moderate quality evidence.

Development of an Online App to Predict Post-Endoscopic Retrograde Cholangiopancreatography Adverse Events Using a Single-Center Retrospective Cohort.

INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP) is a technically demanding procedure with a high risk for adverse events (AEs). AIM: evaluate patient- and procedure-related risk factors for ERCP-related AEs and develop an online app to estimate risk of AEs. METHODS: retrospective study of 1,491 consecutive patients who underwent 1,991 ERCPs between 2012 and 2017 was conducted. AEs definition and severity were classified according to most recent ESGE guidelines. Each variable was tested for association with occurrence of overall AEs, post-ERCP pancreatitis (PEP) and cholangitis. For each outcome, 2 regression models were built, from which an online Shiny-based app was created. RESULTS: Overall AE rate was 15.3%; in 19 procedures, >1 AE occurred. Main post-ERCP AE was PEP (7.5%), followed by cholangitis (4.9%), bleeding (1.3%), perforation (1%), cardiopulmonary events (0.9%), and cholecystitis (0.3%). Seventy-eight percent of AEs were mild/moderate; of severe (n = 55) and fatal (n = 20) AEs, more than half were related to infection, cardiac/pulmonary AEs, and perforation. AE-related mortality rate was 1%. When testing precannulation, procedural covariates, and ERCP findings, AE occurrence was associated with age (odds ratio [OR] 0.991), previous PEP (OR 2.198), ERCP complexity grade III/IV (OR 1.924), standard bile duct cannulation (OR 0.501), sphincterotomy (OR 1.441), metal biliary stent placement (OR 2.014), periprocedural bleeding (OR 3.024), and biliary duct lithiasis (OR 0.673). CONCLUSION: Our app may allow an optimization of the patients' care, by helping in the process of decision-making, not only regarding patient or endoscopist's selection but also definition of an adequate and tailored surveillance plan after the procedure.

Self-expandable metal stents in esophageal cancer before preoperative neoadjuvant therapy: efficacy, safety, and long-term outcomes.

BACKGROUND: Self-expandable metal stent (SEMS) placement for malignant dysphagia before preoperative neoadjuvant therapy (NT) is controversial. AIM: Evaluate SEMS placement impact on clinical and oncologic outcomes in patients with esophageal cancer who underwent surgery after NT. METHODS: Retrospective study of esophageal cancer patients referred for esophagectomy after NT. A propensity score was built consisting of the conditional probability of having had a SEMS given a set of baseline variables. In the SEMS group, patients underwent SEMS placement followed by NT and esophagectomy, whereas in the non-SEMS group, patients underwent only NT and esophagectomy. RESULTS: One hundred patients were included, 29 in the SEMS group and 71 in the non-SEMS group. Median follow-up was 18 months. SEMS-related adverse events occurred in 20.7% of the patients. After propensity score analysis, SEMS use decreased delta dysphagia score (regression coefficient [RC]: - 2.69, 95% CI - 3.18 to - 2.21), dysphagia grade before surgery (RC: - 0.74, 95% CI - 1.22 to - 0.27), hospital readmissions at 1 month (OR 0.18; p = 0.019), but increased overall morbidity after surgery (OR 3.02; p = 0.045). No significant differences were found regarding delta albumin levels and albumin levels before surgery, delta weight and weight before surgery, death related to surgery, number of lymph nodes harvested, R0 resection rate, tumor recurrence, recurrence-free survival, overall survival, and 30-day, 6-month, and 3-year mortality. CONCLUSION: SEMS placement improved dysphagia and allowed patients to maintain an equal nutritional status compared to patients without dysphagia during NT. Although postsurgical morbidity was higher in patients with SEMS placement, postsurgical mortality and oncological outcome were not different.

Self-expandable metal stents for obstructing colonic and extracolonic cancer: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2020.

The following recommendations should only be applied after a thorough diagnostic evaluation including a contrast-enhanced computed tomography (CT) scan. 1 : ESGE recommends colonic stenting to be reserved for patients with clinical symptoms and radiological signs of malignant large-bowel obstruction, without signs of perforation. ESGE does not recommend prophylactic stent placement.Strong recommendation, low quality evidence. 2 : ESGE recommends stenting as a bridge to surgery to be discussed, within a shared decision-making process, as a treatment option in patients with potentially curable left-sided obstructing colon cancer as an alternative to emergency resection.Strong recommendation, high quality evidence. 3 : ESGE recommends colonic stenting as the preferred treatment for palliation of malignant colonic obstruction.Strong recommendation, high quality evidence. 4 : ESGE suggests consideration of colonic stenting for malignant obstruction of the proximal colon either as a bridge to surgery or in a palliative setting.Weak recommendation, low quality evidence. 5 : ESGE suggests a time interval of approximately 2 weeks until resection when colonic stenting is performed as a bridge to elective surgery in patients with curable left-sided colon cancer.Weak recommendation, low quality evidence. 6 : ESGE recommends that colonic stenting should be performed or directly supervised by an operator who can demonstrate competence in both colonoscopy and fluoroscopic techniques and who performs colonic stenting on a regular basis.Strong recommendation, low quality evidence. 7 : ESGE suggests that a decompressing stoma as a bridge to elective surgery is a valid option if the patient is not a candidate for colonic stenting or when stenting expertise is not available.Weak recommendation, low quality evidence.

Role of Peroral Cholangioscopy for Diagnosis and Staging of Biliary Tumors.

OBJECTIVES: Peroral cholangioscopy (POC) has shown to be a useful diagnostic procedure in the evaluation of biliary strictures; however, data regarding its role on preoperative staging are scarce. The aim of this study was to evaluate POC role in the diagnosis and preoperative intraductal staging of perihilar cholangiocarcinoma (CCA). METHODS: Retrospective study that included all patients who underwent POC with SpyGlassTM Direct Visualization System for the diagnosis of biliary strictures or for preoperative evaluation of extrahepatic biliary tumors, between 2015 and 2019, in a single tertiary center. RESULTS: Forty-three patients were included, 63% male with a median age of 62 years. Thirty-eight (88.3%) underwent POC due to indeterminate biliary strictures, 3 (7%) due to bile duct filling defect, and 2 (4.7%) for intraductal staging of perihilar CCA. In the follow-up, a final diagnosis of malignancy was established in 56% of the patients. Visual impression accuracy with SpyGlass was 95.1% (with 100% sensitivity and 89.5% specificity). SpyBite biopsies accuracy was 80.5% (63.6% sensitivity and 100% specificity). In the 19 patients with a final perihilar CCA diagnosis, intraductal evaluation with SpyGlass altered anatomic classification (Bismuth-Corlette) defined by previous imagiologic findings in 8 (42.1%) patients. Alteration in anatomic classification changed therapeutic approach in 4 (21%). CONCLUSIONS: POC use for evaluating intraductal spread in potentially resectable perihilar CCA can detect more extensive and change surgical management. In the future, preoperative staging of perihilar CCA with POC combined with imagiologic evaluation of vascular extension of the lesions may optimize surgical results.

Forced degradation studies of norepinephrine and epinephrine from dental anesthetics: Development of stability-indicating HPLC method and in silico toxicity evaluation.

Injectable solutions containing epinephrine (EPI) and norepinephrine (NE) are not stable, and their degradation is favored mainly by the oxidation of catechol moiety. As studies of these drugs under forced degradation conditions are scarce, herein, we report the identification of their degradation products (DP) in anesthetic formulations by the development of stability-indicating HPLC method. Finally, the risk assessment of the major degradation products was evaluated using in silico toxicity approach. HPLC method was developed to obtain a higher selectivity allowing adequate elution for both drugs and their DPs. The optimized conditions were developed using a C18 HPLC column, sodium 1-octanesulfonate, and methanol (80:20, v/v) as mobile phase, with a flow rate of 1.5 mL/min, UV detection at 199 nm. The analysis of standard solutions with these modifications resulted in greater retention time for EPI and NE, which allow the separation of these drugs from their respective DPs. Then, five DPs were identified and analyzed by in silico studies. Most of the DPs showed important alerts as hepatotoxicity and mutagenicity. To the best of our acknowledgment, this is the first report of a stability-indicating HPLC method that can be used with formulations containing catecholamines.

Lewis score: a useful tool for diagnosis and prognosis in Crohn's disease.

BACKGROUND: videocapsule endoscopy (VCE) is currently the most sensitive diagnostic tool to detect early small bowel inflammation. A Lewis score (LS) of ≥ 135 as the cutoff value for the presence of significant inflammatory activity in patients undergoing VCE for suspected Crohn's disease (CD) has been suggested as a useful tool for the diagnosis of CD. The aim of this study was to evaluate the diagnostic and prognostic accuracy of the LS in patients with suspected CD undergoing VCE. METHODS: a retrospective single-center study was performed that included patients who underwent VCE for suspected CD between January 2010 and December 2015. Inflammatory activity was assessed with the LS. Patients were grouped according to the criteria of the International Conference on Capsule Endoscopy (ICCE) for the definition of suspected CD; group 1: patients not fulfilling ICCE and group 2: patients with ≥ 2 ICCE criteria. RESULTS: one hundred and ninety-one patients were included, 61% were female and the mean age was 39 ± 14 years. VCE detected significant inflammatory activity (LS ≥ 135) in 81 patients (42%); 24 patients from group 1 (32%) and 57 patients from group 2 (50%) (p = 0.014). During a mean follow-up period of 41 ± 21 months (12-79), a CD diagnosis was determined in 60 patients (31%); 55 patients with LS ≥ 135 (92%) and five patients with LS < 135 (5%) (p < 0.001). The LS showed a good diagnostic accuracy with an AUROC of 0.93 (p < 0.001). During the first year after diagnosis, there was a significant association between a higher LS and the need for immunomodulatory therapy, biological therapy, bowel resection surgery or hospital admission due to a CD flare-up. CONCLUSIONS: the LS (cutoff ≥ 135) is very useful in the diagnosis of CD in patients undergoing VCE. Moreover, higher values of this score was associated with prognostic variables.

Sensitive detection of topiramate degradation products by high-performance liquid chromatography/electrospray ionization mass spectrometry using ion-pairing reagents and polarity switching.

RATIONALE: The chromatographic analysis of topiramate and its degradation products is challenging due to the absence of chromophoric moieties in their structures, the wide polarity range of the compounds and their ionization differences. This work proposes two new mass spectrometry approaches for evaluating these analytes. METHODS: Based on the calculated experimental limit of detection (LOD), a highly sensitive high-performance liquid chromatography (HPLC) paired-ion electrospray ionization mass spectrometry (PIESI-MS) method was developed for the determination of topiramate inorganic degradation products. The influence of different solvent systems on the LODs for topiramate and its main degradation products was determined in both positive/negative ionization modes. In addition, a HPLC method to analyze both organic and inorganic degradation products was proposed by mass spectrometry with positive/negative ion switching electrospray ionization. RESULTS: A sensitive HPLC/PIESI-MS method was achieved for the efficient separation of topiramate inorganic degradation products. Both sulfate and sulfamate were detected in the positive selected ion monitoring (SIM) mode with an increased sensitivity compared with the negative SIM mode. The HPLC/ESI-MS analysis with positive/negative ion switching allowed the simultaneous separation and detection of the major degradation products of topiramate in a 10-min run using a single column and a single detector. CONCLUSIONS: Two new alternative MS approaches for analyzing the main degradation products of topiramate were developed. The proposed methods are considered advantageous over the existing methods and can be applied to quality control studies of topiramate.

Development of USP Apparatus 3 Dissolution Method with IVIVC for Extended Release Tablets of Metformin Hydrochloride and Development of a Generic Formulation.

Metformin is a euglycemic drug for the treatment of type 2 diabetes mellitus. To date, there are 13 dissolution methodologies described in the U.S. Pharmacopoeia (USP) to evaluate the release profile of metformin from extended-release tablets utilizing either a USP apparatus 1 (basket) or 2 (paddle). In the absence of a protocol for a USP apparatus 3 (reciprocating cylinder), the goal of this work was to develop an in vitro dissolution method for metformin extended-release tablets based on an in vivo-in vitro correlation (IVIVC). Following a systematic evaluation, a final dissolution method, M4, was defined. It applied 30 dips per minute (dpm) over a total period of 10 h into a series of solutions that included 2 h in HCl media (pH 1.2), 1 h in an acetate buffer solution (pH 4.5), 1 h in phosphate buffer solution (PBS) (pH 5.8) and 6 h in PBS (pH 6.8). This method showed a significant IVIVC with a calculated R2 > 0.98 (point-to-point correlation, Level A) and it was successfully used as a tool to assist in the development of generic extended release formulations for metformin consisting of a lipophilic matrix system.

(Technically) Difficult colonoscope insertion - Tips and tricks.

Cecal intubation is a critical aspect of effective, complete colonoscopy. Difficult colonoscopy is most often considered as one in which it is challenging or impossible to reach the cecum. It may be a common occurrence due to patient and/or endoscopist factors. Incomplete colonoscopies should be avoided, since patients in this context present an important prevalence of lesions that escape examination. The approach to successful cecal intubation should depend on characterization of the problem as redundant colon or difficult sigmoid colon. Most patients with a prior incomplete colonoscopy can be colonoscoped successfully, if careful attention is paid to technique, using a variety of scopes, colonoscopy methods and additional equipment. Sufficient time should be allotted to make the attempt.