Effectiveness of endoscopic ultrasound-guided simple puncture-aspiration (non-stenting) in the management of abdominal collections

Background: Endoscopic management of abdominal collections includes endoscopic ultrasound (EUS)-guided transmural drainage, transpapillar via endoscopic retrograde cholangiopancreatography (ERCP), and EUS-guided simple puncture-aspiration (SPA). The latter is little reported, and there are some doubts about its real usefulness.Objectives: The aim of this study was to assess the effectiveness of EUS-guided SPA as a first-line approach for treatment in selected abdominal collections.Design: Retrospective observational study performed in two tertiary centers (Barcelona area).Methods: Inclusion of all consecutive patients with abdominal collections that underwent EUS-guided SPA from July 2007 to July 2021. The decision was based on endoscopist criteria and collection characteristics. Clinical success was defined as avoidance of an additional interventional approach (endoscopic stenting, percutaneous drainage, surgery).Results: Of 241 patients with abdominal collections treated endoscopically, 55 were included for analysis (mean age, 56 +/- 12 years). Collection features: mean size 63.3 +/- 24.8 mm; positive culture in 22 (40%) and pancreatic nature in 45 (81.8%). EUS-SPA was performed successfully in all cases, and clinical success was achieved in 76.3% (95% confidence interval (CI), 65.5-87.3) of cases (n-42/55). The most frequently used needle size was 19 Ga (85%). A nonsignificant trend for success was detected for noninfected collections (84.8 vs 63.6; p = 0.07) and lower size (mean +/- SD; 60.2 +/- 22.9 vs 73.8 +/- 29 mm; p = 0.09). Two related adverse events were detected: one bleeding and one abdominal pain. Recurrence was detected in five pseudocysts after clinical success. Median follow-up was 629 days (IQR 389-877).Conclusion: EUS-SPA of selected abdominal collections seems to be a safe and effective technique, avoiding a more aggressive strategy such as transmural stenting. EUS-SPA may be a viable alternative in collections with limited size and preferably noninfected

Half of the patients with subepithelial tumours present borderline or pathologic anxiety-distress and carcinophobia: multicentre cohort study

Background and aims: minor nonspecific gastrointestinal sub-epithelial lesions (usually defined by the term 'tumor') are usually associated with a malignant illness and cancer. The aim of this study was to assess anxiety-distress and carcinophobia in patients referred to specialized monographic outpatient clinics for evaluation and treatment of this type of lesion.Methods: prospective, multicenter, cohort study. Specific self-reported questionnaires were used to report threat-ening life-experiences and to assess levels of distress (The Hospital Anxiety and Depression Scale) and cancer-related worries (The Cancer Worry Scale).Results: forty participants were included and analyzed at baseline. Pathologic and borderline anxiety were detected in 13 % (5/40, 95 % CI: 4-27 %) and 35 % (14/40, 95 % CI: 21-52 %) of participants, respectively, whereas, cancer-relat-ed worries (moderate to very high) were observed in 48 % (19/40, 95 % CI: 32-64 %) of participants. Pathologic global distress was identified in 25 % (10/40, 95 % CI: 13-42 %) of subjects. Higher educational level (university studies), a lack of lifetime psychiatric comorbidity and a lack of family history of cancer were associated with less anxiety, global distress and carcinophobia.Conclusions: almost half of the patients diagnosed with a minor nonspecific gastrointestinal subepithelial lesion pre-sented anxiety-distress and/or carcinophobia. Specific associ-ations with anxiety-distress reaction and fears were detected

Outcomes of a multicenter registry on EUS-guided gallbladder drainage as a rescue technique for malignant distal biliary obstruction after failed endoscopic retrograde cholangiopancreatography

Background and Objectives: Endoscopic retrograde cholangiopancreatography (ERCP) is the primary intervention for malignant distal biliary obstruction (MDBO). However, ERCP may fail for various reasons, requiring alternative interventions such as EUS-guided biliary drainage. Among EUS-guided biliary drainage (EUS-BD) methods, EUS-guided gallbladder drainage (EUS-GBD) is emerging as a viable option for patients who have failed ERCP and EUS-BD. The aim of this study is to evaluate the efficacy and safety of EUS-GBD as salvage therapy for MDBO and its potential role in allowing the initiation of chemotherapy. Methods: This is a retrospective multicenter study of consecutive patients with MDBO with failed ERCP and/or EUS-BD that subsequently underwent EUS-GBD with lumen-apposing metal stent. Results: Ninety-six patients from 9 centers in Spain were included. Technical success was achieved in 99% of patients, while clinical success, defined as bilirubin reduction <50% within 14 days after the procedure, was achieved in 78.1% of patients. Bilirubin levels were normalized in 65.6% of patients. The median time to normalization of bilirubin levels was 15 (7-27) days. Related to continuation of oncological treatment, 44/77 (57.1%) eligible patients were able to start chemotherapy after the procedure, and 12/17 (70.6%) eligible patients underwent surgery in the end. Adverse events were observed in 26.3% of cases, with 3 patients requiring surgery and 3 deaths related to EUS-GBD. Conclusions: EUS-GBD represents a potential alternative to MDBO in cases where ERCP has failed, with an appropriate profile of patients starting chemotherapy. However, in light of the considerable number of adverse events and the moderate efficacy, it may be advisable to consider this approach as a second-line option

Multicenter study of lumen-apposing metal stents with or without pigtail in endoscopic ultrasound-guided biliary drainage for malignant obstruction - BAMPI TRIAL: an open-label, randomized controlled trial protocol

Background It is unclear whether the insertion of an axis-orienting double-pigtail plastic stent (DPS) through biliary lumen-apposing meal stent (LAMS) in EUS-guided choledochoduodenostomy (CDS) improves the stent patency. The aim of this study is to determine whether this technical variant offers a clinical benefit in EUS-guided biliary drainage (BD) for the management of distal malignant biliary obstruction. Methods/design This is a multicenter open-label, randomized controlled trial with two parallel groups. Eighty-four patients with malignant biliary obstruction will undergo EUS-BD (CDS type) using LAMS in 7 tertiary hospitals in Spain and will be randomized to the LAMS and LAMS plus DPS groups. The primary endpoint is the rate of recurrent biliary obstruction, as a stent dysfunction parameter, detected during follow-up. Secondary endpoints: technical and clinical success (reduction in bilirubin > 50% within 14 days of stent placement), safety, and others (number of reinterventions, time to biliary obstruction, prognostic factors, survival rate). Discussion The BAMPI trial has been designed to determine whether the addition of a coaxial axis-orienting DPS through LAMS is superior to LAMS alone to prevent stent dysfunction

Postural control is not systematically related to reading skills:implications for the assessment of balance as a risk factor for developmental dyslexia

Impaired postural control has been associated with poor reading skills, as well as with lower performance on measures of attention and motor control variables that frequently co-occur with reading difficulties. Measures of balance and motor control have been incorporated into several screening batteries for developmental dyslexia, but it is unclear whether the relationship between such skills and reading manifests as a behavioural continuum across the range of abilities or is restricted to groups of individuals with specific disorder phenotypes. Here were obtained measures of postural control alongside measures of reading, attention and general cognitive skills in a large sample of young adults (n = 100). Postural control was assessed using centre of pressure (CoP) measurements, obtained over 5 different task conditions. Our results indicate an absence of strong statistical relationships between balance measures with either reading, cognitive or attention measures across the sample as a whole. © 2014 Loras et al

Endoscopic treatment (endoscopic balloon dilation/self-expandable metal stent) vs surgical resection for the treatment of de novo stenosis in Crohn's disease (ENDOCIR study): an open-label, multicentre, randomized trial.

Background: Stenosis is one of the most common complications in patients with Crohn's disease (CD). Endoscopic balloon dilation (EBD) is the treatment of choice for a short stenosis adjacent to the anastomosis from previous surgery. Self-expandable metal stents (SEMS) may be a suitable treatment option for longer stenoses. To date, however, there is no scientific evidence as to whether endoscopic (EBD/SEMS) or surgical treatment is the best approach for de novo or primary stenoses that are less than 10 cm in length. Methods/design: Exploratory study as "proof-of-concept", multicentre, open-label, randomized trial of the treatment of de novo stenosis in the CD; endoscopic treatment (EBD/SEMS) vs surgical resection (SR). The type of endoscopic treatment will initially be with EDB; if a therapeutic failure occurs, then a SEMS will be placed. We estimate 2 years of recruitment and 1 year of follow-up for the assessment of quality of life, costs, complications, and clinical recurrence. After the end of the study, patients will be followed up for 3 years to re-evaluate the variables over the long term. Forty patients with de novo stenosis in CD will be recruited from 15 hospitals in Spain and will be randomly assigned to the endoscopic or surgical treatment groups. The primary aim will be the evaluation of the patient quality of life at 1 year follow-up (% of patients with an increase of 30 points in the 32-item Inflammatory Bowel Disease Questionnaire (IBDQ-32). The secondary aim will be evaluation of the clinical recurrence rate, complications, and costs of both treatments at 1-year follow-up. Discussion: The ENDOCIR trial has been designed to determine whether an endoscopic or surgical approach is therapeutically superior in the treatment of de novo stenosis in CD

Bi-allelic variants in IPO8 cause a connective tissue disorder associated with cardiovascular defects, skeletal abnormalities, and immune dysregulation.

Dysregulated transforming growth factor TGF-β signaling underlies the pathogenesis of genetic disorders affecting the connective tissue such as Loeys-Dietz syndrome. Here, we report 12 individuals with bi-allelic loss-of-function variants in IPO8 who presented with a syndromic association characterized by cardio-vascular anomalies, joint hyperlaxity, and various degree of dysmorphic features and developmental delay as well as immune dysregulation; the individuals were from nine unrelated families. Importin 8 belongs to the karyopherin family of nuclear transport receptors and was previously shown to mediate TGF-β-dependent SMADs trafficking to the nucleus in vitro. The important in vivo role of IPO8 in pSMAD nuclear translocation was demonstrated by CRISPR/Cas9-mediated inactivation in zebrafish. Consistent with IPO8's role in BMP/TGF-β signaling, ipo8-/- zebrafish presented mild to severe dorso-ventral patterning defects during early embryonic development. Moreover, ipo8-/- zebrafish displayed severe cardiovascular and skeletal defects that mirrored the human phenotype. Our work thus provides evidence that IPO8 plays a critical and non-redundant role in TGF-β signaling during development and reinforces the existing link between TGF-β signaling and connective tissue defects

UNC45A deficiency causes microvillus inclusion disease–like phenotype by impairing myosin VB–dependent apical trafficking

International audienceVariants in the UNC45A cochaperone have been recently associated with a syndrome combining diarrhea, cholestasis, deafness, and bone fragility. Yet the mechanism underlying intestinal failure in UNC45A deficiency remains unclear. Here, biallelic variants in UNC45A were identified by next-generation sequencing in 6 patients with congenital diarrhea. Corroborating in silico prediction, variants either abolished UNC45A expression or altered protein conformation. Myosin VB was identified by mass spectrometry as client of the UNC45A chaperone and was found misfolded in UNC45A(KO) Caco-2 cells. In keeping with impaired myosin VB function, UNC45A(KO) Caco-2 cells showed abnormal epithelial morphogenesis that was restored by full-length UNC45A, but not by mutant alleles. Patients and UNC45A(KO) 3D organoids displayed altered luminal development and microvillus inclusions, while 2D cultures revealed Rab11 and apical transporter mislocalization as well as sparse and disorganized microvilli. All those features resembled the subcellular abnormalities observed in duodenal biopsies from patients with microvillus inclusion disease. Finally, microvillus inclusions and shortened microvilli were evidenced in enterocytes from unc45a-deficient zebrafish. Taken together, our results provide evidence that UNC45A plays an essential role in epithelial morphogenesis through its cochaperone function of myosin VB and that UNC45A loss causes a variant of microvillus inclusion disease

Diagnostic yield of next-generation sequencing in very early-onset inflammatory bowel diseases: a multicenter study (vol 12, pg 1104, 2021)

Transplantation and immunomodulatio