Double-Blind Multicenter Randomized Clinical Trial Comparing Glucagon vs Placebo in the Resolution of Alimentary Esophageal Impaction.

INTRODUCTION: The aim of this study was to compare the effectiveness of glucagon vs placebo in resolving esophageal foreign body impaction (EFBI), as well as the length of the procedure and adverse events. METHODS: This was a multicenter, randomized, double-blind trial involving consecutive patients diagnosed with alimentary EFBI. Participants were randomized to receive either 1 mg of intravenous glucagon or placebo. All patients underwent upper endoscopy, and adverse events were assessed through a protocolized telephonic interview 7 days later. RESULTS: The study included 72 subjects in the glucagon group and 68 in the placebo group. The foreign body was not identified in 23.6% of subjects in the glucagon group and 20.6% of subjects in the placebo group (difference 3%, 95% confidence interval -10.7% to 16.8%, P = 0.67). The median time required to remove the foreign body was similar in both groups 4 minutes (range 2-10) in the glucagon group and 3.5 minutes (range 2-7) in the placebo group (difference 0.5 minutes, 95% confidence interval -1.3 to 2.3; P = 0.59). The most common adverse event reported in both groups was mild pharyngeal pain. DISCUSSION: Glucagon is no more effective than placebo in resolving EFBI or shortening the time required to remove the foreign body (EUDRA-CT number 2019-004920-40).

Endoscopic ultrasound-guided gallbladder drainage with long-term lumen-apposing metal stent indwell: 1-year results from a prospective nationwide observational study.

BACKGROUND AND AIM: This study aimed to determine safety and risk factors for adverse events (AEs) of endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) with long-term indwell of lumen-apposing metal stents (LAMS). METHODS: This study is a multicenter prospective observational study on consecutive high surgical-risk patients requiring gallbladder drainage who underwent EUS-GBD with LAMS over 12 months. Centralized telephone follow-up interviews were conducted every 3 months for 1 year. Patients were censored at LAMS removal, cholecystectomy, or death. AE-free survival was determined using log-rank tests. Cumulative risks were estimated using life-table analysis. RESULTS: Eighty-two patients were included (53.7% male, median [interquartile range] age of 84.6 [76.5-89.8] years, and 85.4% with acute cholecystitis). Technical success was achieved in 79 (96.3%), and clinical success in 73 (89%). No patient was lost to follow-up; 45 patients (54.9%) completed 1-year follow-up with in situ LAMS. Median (interquartile range) LAMS indwell time was 364 (47-367) days. Overall, 12 (14.6%) patients presented 14 AEs, including 5 (6.1%) recurrent biliary events (3 acute cholangitis, 1 mild acute pancreatitis, and 1 acute cholecystitis). Patients with pancreatobiliary malignancy had an increased risk of recurrent biliary events (33% vs 1.5%, P = 0.001). The overall 1-year cumulative risk of recurrent biliary events was 9.7% (4.1-21.8%). The 1-year risk of AEs and of severe AEs was 18.8% (11-31.2%) and 7.9% (3.3-18.2%), respectively. Pancreatobiliary malignancy was the single risk factor for recurrent biliary events; LAMS misdeployment was the strongest risk factor for AEs. CONCLUSIONS: Long-term LAMS indwell does not increase the risk of delayed AEs following EUS-GBD.

Could driving help us to "see better"? A comparative assessment of saccadic efficiency, visual speed, and attention.

BACKGROUND: This study aimed at comparing drivers' and non-drivers' results in the Adult Developmental Eye Movement with Distractors test (ADEMd) and the Useful Field of View test (UFOV). METHODS: One hundred and twenty Spaniards (mean age 50.90 ± 17.32 years) without eye disease voluntarily participated in this cross-sectional descriptive study. Participants in a single experimental session completed a questionnaire on sociodemographic, health, eyesight, and driving information. They also performed the ADEMd and UFOV tests randomly following standardized protocols. The ADEMd is a visual-verbal test that measures saccadic efficiency and visual attention. Brown-Forsythe (B-F) tests with Games-Howell post-hoc adjustments were conducted to assess differences between groups. Groups were formed according to sex, age (young adults, adults, and older adults), and driver/non-driver for further analysis. Additionally, associations between dependent variables were assessed through Spearman's correlations. RESULTS: Drivers obtained significantly better results in the ADEMd compared with non-drivers. Non-significant differences between drivers and non-drivers were encountered in the UFOV. Additionally, significant differences were observed between sexes and age groups. It is worth highlighting that non-driver's age significantly correlated with worse ADEMd performance (rho = .637 to .716). This correlation was non-significant in drivers. Similarly, reading hours significantly correlated with better ADEMd performance in non-drivers (rho = - .291 to - .363), but not in drivers. The only significant correlations between ADEMd and UFOV tests were found in drivers (rho = .307 to .410). CONCLUSION: Considering all the discussed results, it could be hypothesized that the driving task promotes abilities, such as oculomotor and cognitive function, which are relevant for the performance in the ADEMd. However, this hypothesis is based on correlational outcomes and further studies should causally assess this possible relation.

Description of a new method to calculate the equator of the crystalline lens using AS-OCT images: Accuracy in non-dilated measurements.

OBJECTIVE: To establish a methodology for objectively estimating the Lens Equatorial Plane (LEP) from clinical images, comparing LEP with dilated versus non-dilated pupils. METHODS: A cohort of 91 eyes from 60 patients undergoing preoperative assessments for cataract surgery was evaluated. Anterior Segment Optical Coherence Tomography (AS-OCT) images were analysed under conditions of pharmacologically induced pupil dilation versus a non-dilated pupil. Geometrical parameters, including LEP, intersection diameter (ID), lens thickness (LT), anterior and posterior lens thickness were automatically calculated by applying standard image processing techniques to clinical AS-OCT images. RESULTS: Significant differences in lens parameters, including LEP, were observed between dilated and non-dilated conditions (all p < 0.001). A strong linear correlation was found across all geometrical variables under both conditions (r[LEP] = 0.64, r[ID] = 0.78, r[LT] = 0.99, all p < 0.001); enabling reliable correction of these differences. CONCLUSION: The study introduces an objective methodology for LEP calculation, emphasising the need to consider the eye's physiological state during preoperative measurements. Incorporating LEP into future intraocular lens (IOL) power calculation formulas and replacing the habitual effective lens position may potentially improve the accuracy of IOL power estimation and thus postoperative visual outcomes.

Long-Term Outcomes of Biological Therapy in Crohn's Disease Complicated With Internal Fistulizing Disease: BIOSCOPE Study From GETECCU.

INTRODUCTION: The prevalence of penetrating complications in Crohn's disease (CD) increases progressively over time, but evidence on the medical treatment in this setting is limited. The aim of this study was to evaluate the effectiveness of biologic agents in CD complicated with internal fistulizing disease. METHODS: Adult patients with CD-related fistulae who received at least 1 biologic agent for this condition from the prospectively maintained ENEIDA registry were included. Exclusion criteria involved those receiving biologics for perianal disease, enterocutaneous, rectovaginal, anastomotic, or peristomal fistulae. The primary end point was fistula-related surgery. Predictive factors associated with surgery and fistula closure were evaluated by multivariate logistic regression and survival analyses. RESULTS: A total of 760 patients from 53 hospitals (673 receiving anti-tumor necrosis factors, 69 ustekinumab, and 18 vedolizumab) were included. After a median follow-up of 56 months (interquartile range, 26-102 months), 240 patients required surgery, with surgery rates of 32%, 41%, and 24% among those under anti-tumor necrosis factor, vedolizumab, or ustekinumab, respectively. Fistula closure was observed in 24% of patients. Older patients, ileocolonic disease, entero-urinary fistulae, or an intestinal stricture distal to the origin of the fistula were associated with a higher risk of surgery, whereas nonsmokers and combination therapy with an immunomodulator reduced this risk. DISCUSSION: Biologic therapy is beneficial in approximately three-quarters of patients with fistulizing CD, achieving fistula closure in 24%. However, around one-third still undergo surgery due to refractory disease. Some patient- and lesion-related factors can identify patients who will obtain more benefit from these drugs.

Prospective multicenter assessment of the impact of EUS-guided gastroenterostomy on patient quality of life in unresectable malignant gastric outlet obstruction.

BACKGROUND AND AIMS: EUS-guided gastroenterostomy (EUS-GE) is increasingly used for malignant gastric outlet obstruction (GOO) in inoperable patients. However, the impact of EUS-GE on patient quality of life (QoL) has not been evaluated prospectively. METHODS: Consecutive patients with unresectable malignant GOO who underwent EUS-GE between August 2019 and May 2021 at 4 Spanish centers were prospectively assessed using the European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 at baseline and 1 month after the procedure. Centralized follow-up by telephone calls was undertaken. The Gastric Outlet Obstruction Scoring System (GOOSS) was used to assess oral intake, defining clinical success as a GOOSS ≥2. Differences between baseline and 30-day QoL scores were assessed using a linear mixed model. RESULTS: Sixty-four patients were enrolled, 33 (51.6%) men, with a median age of 77.3 years (interquartile range, 65.5-86.5). The most common diagnoses were pancreatic (35.9%) and gastric (31.3%) adenocarcinoma. Thirty-seven patients (57.9%) presented a 2/3 baseline Eastern Cooperative Oncology Group performance status score. Oral intake was restarted within 48 hours in 61 patients (95.3%), and the median postprocedure hospital stay was 3.5 days (interquartile range, 2-5). The 30-day clinical success rate was 83.3%. A clinically significant increase of 21.6 points (95% confidence interval, 11.5-31.7) in the global health status scale was documented, with significant improvements in nausea and vomiting, pain, constipation, and appetite loss. CONCLUSIONS: EUS-GE relieves GOO symptoms in patients with unresectable malignancy, allowing rapid oral intake and hospital discharge. It also provides a clinically relevant increase in QoL scores at 30 days from baseline. (Clinical trial registration number: NCT04660695.).

Endoscopic removal of lumen-apposing metal stents - risk factors for stent embedment, complex removals, and adverse events: analysis from a multicenter prospective case series.

BACKGROUND: Removing lumen-apposing metal stents (LAMSs) may be difficult and even harmful, but these features have seldom been analyzed. We aimed to generate a comprehensive assessment of the feasibility and safety of LAMS retrieval procedures. METHODS: A prospective multicenter case series including all technically successfully deployed LAMSs between January 2019 and January 2020 that underwent endoscopic stent removal. All retrieval-related data were prospectively recorded using standardized telephone questionnaires as part of centralized follow-up that ended after stent removal had been performed. Multivariable logistic regression models assessed the potential risk factors for complex removal. RESULTS: For the 407 LAMSs included, removal was attempted in 158 (38.8 %) after an indwell time of 46.5 days (interquartile range [IQR] 31-70). The median (IQR) removal time was 2 (1-4) minutes. Removal was labelled as complex in 13 procedures (8.2 %), although advanced endoscopic maneuvers were required in only two (1.3 %). Complex removal risk factors were stent embedment (relative risk [RR] 5.84, 95 %CI 2.14-15.89; P = 0.001), over-the-wire deployment (RR 4.66, 95 %CI 1.60-13.56; P = 0.01), and longer indwell times (RR 1.14, 95 %CI 1.03-1.27; P = 0.01). Partial and complete embedment were observed in 14 (8.9 %) and five cases (3.2 %), respectively. The embedment rate during the first 6 weeks was 3.1 % (2/65), reaching 15.9 % (10/63) during the following 6 weeks (P = 0.02). The adverse event rate was 5.1 %, including seven gastrointestinal bleeds (5 mild, 2 moderate). CONCLUSIONS: LAMS removal is a safe procedure, mostly requiring basic endoscopic techniques attainable in conventional endoscopy rooms. Referral to advanced endoscopy units should be considered for stents with known embedment or long indwell times, which may require more technically demanding procedures.

Erdafitinib in the Treatment of Metastatic Urothelial Carcinoma.

A Hispanic man, aged 42 years, was diagnosed with stage IV metastatic urothelial bladder cancer (MUBC) with nonregional lymphadenopathies and lung, bone, and skin involvement. He received first-line treatment with gemcitabine and cisplatin for 6 cycles, achieving a partial response (PR). Next, he received immunotherapy maintenance with avelumab for 4 months until disease progression. A next-generation sequencing test of paraffin-embedded tumor tissue identified a fibroblast growth factor receptor 3 (FGFR3) S249C missense mutation.

Risk factors determining adherence to tyrosine kinase inhibitors in chronic myeloid leukaemia.

OBJECTIVE: Tyrosine kinase inhibitors (TKIs) have successfully changed the natural course of chronic myeloid leukaemia (CML). Although they are highly effective drugs, their clinical benefit is conditioned by adherence. This study aims to analyse the adherence of CML patients treated with TKIs and to identify the main factors influencing their adherence to TKIs treatment. MATERIAL AND METHODS: An 8-month prospective, observational, multicentre study which included patients diagnosed with CML on treatment with TKIs attending the outpatient departments (OPD) of the Pharmacy Services of the participating hospitals. Adherence was assessed using two methods: the Simplified Medication Adherence Questionnaire (SMAQ) and the register of treatment dispensations from the OPDs. To analyse the predictors of adherence, a questionnaire was developed to report demographic and socio-economic information on the patients. RESULTS: A total of 130 patients enrolled in this study. Adherence rate was 56.9% (n = 74) among individuals, not conditioned by the type of drug used: imatinib (54.8%), nilotinib (63.6%) or dasatinib (54.3%) (p = 0.67). The patient educational level (p = 0.047) and employment status (p = 0.028) were predictors of non-adherence to treatment. CONCLUSIONS: Adherence is one of the most relevant parameters affecting the effectiveness of highly effective chronic treatments. Approximately half of our patients showed inadequate adherence to treatment with TKIs, with employment status and the individual's level of education emerging as the determining factors.

Electrochemical monitoring of enzymatic cleavage in nanochannels with nanoparticle-based enhancement: determination of MMP-9 biomarker.

For the first time the use of nanoparticles as carriers of an enzymatic substrate immobilized inside nanoporous alumina membranes is proposed with the aim of amplifying the nanochannel blocking produced and, consequently, improving the efficiency of an enzyme determination through enzymatic cleavage. Streptavidin-modified polystyrene nanoparticles (PSNPs) are proposed as carrier agents, contributing to the steric and the electrostatic blockage due to the charge they present at different pH values. Electrostatic blockage is the predominant effect that governs the blockage in the interior of the nanochannel and is dependent not just in the charge inside the channel, but also in the polarity of the redox indicator used. Hence, the effect of using negatively charged ([Fe(CN)6]4-) and positively charged ([Ru(NH3)6]3+) redox indicator ions is studied for the first time. Under the optimum conditions, matrix-metalloproteinase 9 (MMP-9) is detected at clinically relevant levels (100-1200 ng/mL) showing a detection limit of 75 ng/mL and a quantification limit of 251 ng/mL with good reproducibility (RSD: 8%) and selectivity, also showing an excellent performance in real samples with acceptable recovery percentages (in the range around 80-110%). Overall, our approach represents a cheap and fast sensing methodology of great potential in point-of-care diagnostics.

Prospective cohort study to evaluate premedication with simethicone and n-acetilcysteine for upper diagnostic gastrointestinal endoscopy.

INTRODUCTION: The use of premedication for upper gastrointestinal endoscopy (UGE) is not widely established in western countries. The primary aim of the study was to compare gastric visibility according to the total visibility score (TVS). The secondary aim was to assess complications, diagnostic yield, endoscopic procedure time, sedation dose and patient satisfaction. METHODS: A single center prospective cohort study was performed of consecutive adults undergoing an UGE in the afternoon working shift. After completing enrolment in the control group, patients were administered 200 mg simethicone and 500 mg N-acetylcysteine diluted in 100 ml of water >15 minutes before the procedure. All procedures were recorded and a single, blinded endoscopist evaluated the TVS after recruitment of both cohorts. Patient satisfaction was evaluated using the Spanish translation of the American Society of Gastrointestinal Endoscopy satisfaction questionnaire. RESULTS: 205 patients were included in the study, 103 females (50.2%) with a median age of 54.8-years (IQR: 41.2-65.2). 104 were enrolled to the control group and 101 to the intervention group. Patients receiving premedication presented a higher rate of adequate (74.3% vs 45.2; difference 95% CI: 16,3-41,9%, p<0.001) and excellent gastric visibility (23.8% vs 7.7%; difference 95% CI: 6,3-25,8%, p=0.002). Propofol dose was similar, although the median procedure time was lower in the group of no intervention [5 (IQR: 4-7) vs 6 minutes (IQR: 5-7); p=0.03]. Procedure related adverse events were similar, except that patient without premedication experienced more nausea episodes. Major and minor endoscopic findings and the satisfaction questionnaire showed no differences between both groups. CONCLUSION: Patients receiving premedication with simethicone and N-acetylcysteine had a better gastric visibility score, without any increase in adverse events or affecting the patients' satisfaction.

The Eschenmoser's Salt as a Formylation Agent for the Synthesis of Indolizinecarbaldehydes and Their Use for Colorimetric Nitrite Detection.

C-H bond formylation is the most immediate way to incorporate the versatile formyl group into (hetero)aromatics. However, the type of reagents and severe conditions involved in the classical formylation methods often curtail their application, especially in the presence of other functional groups. Herein, we present the Eschenmoser's salt, a commercially available (dimethylamino)methylating chemical, as a useful reagent for the C-H formylation of indolizines and other compounds. The method is straightforward and mild, furnishing indolizinecarbaldehydes in modest-to-good yields with exclusive and remote regioselectivity. Furthermore, these compounds can be easily transformed into push-pull dyes and are highly selective in the colorimetric detection of nitrite, a substance extensively employed as preservative in the food industry, the concentration of which is crucial to control to prevent harmful effects in living organisms. The assay is simple, allowing the naked-eye detection of nitrite in solution or on a cotton swab for a wide range of concentrations.

Efficacy and safety of cold versus hot snare polypectomy for small (5-9 mm) colorectal polyps: a multicenter randomized controlled trial.

BACKGROUND: Resection techniques for small polyps include cold snare polypectomy (CSP) and hot snare polypectomy (HSP). This study compared CSP and HSP in 5-9 mm polyps in terms of complete resection and adverse events. METHODS: This was a multicenter, randomized trial conducted in seven Spanish centers between February and November 2019. Patients with ≥ 1 5-9 mm polyp were randomized to CSP or HSP, regardless of morphology or pit pattern. After polypectomy, two marginal biopsies were submitted to a pathologist who was blinded to polyp histology. Complete resection was defined as normal mucosa or burn artifacts in the biopsies. Abdominal pain was only assessed in patients without < 5 mm or > 9 mm polyps. RESULTS: 496 patients were randomized: 237 (394 polyps) to CSP and 259 (397 polyps) to HSP. Complete polypectomy rates were 92.5 % with CSP and 94.0 % with HSP (difference 1.5 %, 95 % confidence interval -1.9 % to 4.9 %). Intraprocedural bleeding occurred during three CSPs (0.8 %) and seven HSPs (1.8 %) (P = 0.34). One lesion per group (0.4 %) presented delayed hemorrhage. Post-colonoscopy abdominal pain presented similarly in both groups 1 hour after the procedure (CSP 18.8 % vs. HSP 18.4 %) but was higher in the HSP group after 5 hours (5.9 % vs. 16.5 %; P = 0.02). A higher proportion of patients were asymptomatic 24 hours after CSP than after HSP (97 % vs. 86.4 %; P = 0.01). CONCLUSIONS: We observed no differences in complete resection and bleeding rates between CSP and HSP. CSP reduced the intensity and duration of post-colonoscopy abdominal pain.

Photosensitized selective semi-oxidation of tetrahydroisoquinoline: a singlet oxygen path.

Selective semi-oxidation of tetrahydroisoquinoline (THIQ) leads to a valuable dihydroisoquinoline (DHIQ) derivative via singlet oxygen photooxidation process. Typical photosensitisers (i.e., Ru complexes) can activate the reaction even under heterogeneous conditions that facilitate catalyst separation and reusability. In contrast to DHIQ, THIQ acts as an efficient singlet oxygen quencher driving the reaction selectivity. The reaction can also be facilitated by semiconductor catalysts such as MoCo@GW, a glass wool-based catalyst that is easy to separate and reuse and compatible with flow photochemistry. Its role is to mediate the formation of isoquinoline (IQ) and thus an in situ-generated singlet oxygen catalyst. Laser flash photolysis with NIR detection provides proof of the singlet oxygen mechanism proposed and rate constants for the key steps that mediate the oxidation.

Metastatic Renal Cell Carcinoma With Sarcomatoid Features.

A previously healthy woman, aged 38 years, presented with a 3-month history of fatigue, dyspnea on exertion, significant weight loss, and severe left flank pain; her symptoms restricted any work activities. Laboratory test results were notable for hypercalcemia (corrected serum calcium, 12.8 mg/dL), anemia (9.3 g/dL), and lactate dehydrogenase elevation (>1.5 times the upper limit of normal). A CT scan revealed a 14-cm left renal mass and multiple lung and mediastinal lymph node metastases. A surgical open biopsy was performed; histopathological analysis concluded clear cell renal carcinoma (RCC) with 30% sarcomatoid features. The patient was diagnosed with International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) poor-risk metastatic RCC with sarcomatoid features. She started first-line systemic treatment.

A Case Study on Vestibular Sensations in Driving Simulators.

Motion platforms have been used in simulators of all types for several decades. Since it is impossible to reproduce the accelerations of a vehicle without limitations through a physically limited system (platform), it is common to use washout filters and motion cueing algorithms (MCA) to select which accelerations are reproduced and which are not. Despite the time that has passed since their development, most of these algorithms still use the classical washout algorithm. In the use of these MCAs, there is always information that is lost and, if that information is important for the purpose of the simulator (the training simulators), the result obtained by the users of that simulator will not be satisfactory. This paper shows a case study where a BMW 325Xi AUT fitted with a sensor, recorded the accelerations produced in all degrees of freedom (DOF) during several runs, and data have been introduced in mathematical simulation software (washout + kinematics + actuator simulation) of a 6DOF motion platform. The input to the system has been qualitatively compared with the output, observing that most of the simulation adequately reflects the input to the system. Still, there are three events where the accelerations are lost. These events are considered by experts to be of vital importance for the outcome of a learning process in the simulator to be adequate.

Valorization of CO2 through the Synthesis of Cyclic Carbonates Catalyzed by ZIFs.

One way to exploit CO2 is to use it as a feedstock for the production of cyclic carbonates via its reaction with organic epoxides. As far as we know, there is still no heterogeneous catalyst that accelerates the reaction in a selective, efficient and industrially usable way. Cobalt and zinc-based zeolitic imidazole frameworks (ZIFs) have been explored as heterogeneous catalysts for this reaction. In particular, we have prepared ZIF-8 and ZIF-67 catalysts, which have been modified by partial replacement of 2-methylimidazole by 1,2,4-triazole, in order to introduce uncoordinated nitrogen groups with the metal. The catalysts have shown very good catalytic performance, within the best of the heterogeneous catalysts tested in the cycloaddition of CO2 with epichlorohydrin. The catalytic activity is due ultimately to defects on the outer surface of the crystal, and varies in the order of ZIF-67-m > ZIF-67 > ZiF-8-m = ZIF-8. Notably, reactions take place under mild reaction conditions and without the use of co-catalysts.

Reply to: "Does it matter which plastic stents we use for the treatment of post-surgical leaks? Or is it a one-size-fits-all?"

We appreciate the interest of Sánchez-Luna et al. in our article "Endoscopic internal drainage using transmural double-pigtail stents in leaks following upper gastrointestinal tract surgery", and find their suggestion about using softer urological double pigtail stents (DPS) for endoscopic internal drainage (EID) interesting.

Glutaminase isoforms expression switches microRNA levels and oxidative status in glioblastoma cells.

BACKGROUND: Glutaminase isoenzymes GLS and GLS2 play apparently opposing roles in cancer: GLS acts as an oncoprotein, while GLS2 (GAB isoform) has context specific tumour suppressive activity. Some microRNAs (miRNAs) have been implicated in progression of tumours, including gliomas. The aim was to investigate the effect of GLS and GAB expression on both miRNAs and oxidative status in glioblastoma cells. METHODS: Microarray profiling of miRNA was performed in GLS-silenced LN229 and GAB-transfected T98G human glioblastoma cells and their wild-type counterparts. Results were validated by real-time quantitative RT-PCR. Oxidative status and antioxidant enzymes were determined by spectrophotometric or fluorescence assays in GLS-silenced LN229 and T98G, and GAB-transfected LN229 and T98G. RESULTS: MiRNA-146a-5p, miRNA-140-3p, miRNA-21-5p, miRNA-1260a, and miRNA-92a-3p were downregulated, and miRNA-1246 was upregulated when GLS was knocked down. MiRNA-140-3p, miRNA-1246, miRNA-1260a, miRNA-21-5p, and miRNA-146a-5p were upregulated when GAB was overexpressed. Oxidative status (lipid peroxidation, protein carbonylation, total antioxidant capacity, and glutathione levels), as well as antioxidant enzymes (catalase, superoxide dismutase, and glutathione reductase) of silenced GLS glioblastoma cells and overexpressed GAB glioblastoma cells significantly changed versus their respective control glioblastoma cells. MiRNA-1246, miRNA-1260a, miRNA-146a-5p, and miRNA-21-5p have been characterized as strong biomarkers of glioblastoma proliferation linked to both GLS silencing and GAB overexpression. Total glutathione is a reliable biomarker of glioblastoma oxidative status steadily associated to both GLS silencing and GAB overexpression. CONCLUSIONS: Glutaminase isoenzymes are related to the expression of some miRNAs and may contribute to either tumour progression or suppression through certain miRNA-mediated pathways, proving to be a key tool to switch cancer proliferation and redox status leading to a less malignant phenotype. Accordingly, GLS and GAB expression are especially involved in glutathione-dependent antioxidant defence.

The role of endoscopic ultrasound guidance for biliary and pancreatic duct access and drainage to overcome the limitations of ERCP: a retrospective evaluation.

BACKGROUND: Endoscopic ultrasound (EUS)-guided ductal access and drainage (EUS-DAD) of biliary/pancreatic ducts after failed endoscopic retrograde cholangiopancreatography (ERCP) is less invasive than percutaneous transhepatic biliary drainage (PTBD). The actual need for EUS-DAD remains unknown. We aimed to determine how often EUS-DAD is needed to overcome ERCP failure. METHODS: Consecutive duct access procedures (n = 2205; 95 % biliary) performed between June 2013 and November 2015 at a tertiary-care center were reviewed. ERCP was used first line, EUS-DAD as salvage after ERCP, and PTBD when both had failed. Procedures were defined as "index" in patients without prior endoscopic duct access and "combined" when EUS-DAD followed successful ERCP. The main outcomes were the EUS-DAD and PTBD rates. RESULTS: EUS-DAD was performed in 7.7 % (170/2205) of overall procedures: 9.1 % (116/1274) index and 5.8 % (54/931) follow-up. Most index EUS-DADs were performed following (46 %) or anticipating (39 %) ERCP failure, whereas 15 % followed successful ERCP (combined procedures). Among index procedures, the EUS-DAD rate was higher in surgically altered anatomy (58.2 % [39 /67)] vs. 6.4 % [77/1207]); PTBD was required in 0.2 % (3/1274). Among follow-up procedures, ERCP represented 85.7 %, cholangiopancreatography through mature transmural fistulas 8.5 %, and EUS-DAD 5.8 %; no patient required PTBD. The secondary PTBD rate was 0.1 % (3/2205). Six primary PTBDs were performed (overall PTBD rate 0.4 % [9/2205]). CONCLUSIONS: EUS-DAD was required in 7.7 % of ERCPs for benign and malignant biliary/pancreatic duct indications. Salvage PTBD was required in 0.1 %. This high EUS-DAD rate reflects disease complexity, a wide definition of ERCP failure, and restrictive PTBD use, not poor ERCP skills. EUS-DAD effectively overcomes the limitations of ERCP eliminating the need for primary and salvage PTBD in most cases.