Randomized controlled trial of nasogastric tube use after esophagectomy: study protocol for the kinetic trial.

Esophagectomy is a complex and complication laden procedure. Despite centralization, variations in perioparative strategies reflect a paucity of evidence regarding optimal routines. The use of nasogastric (NG) tubes post esophagectomy is typically associated with significant discomfort for the patients. We hypothesize that immediate postoperative removal of the NG tube is non-inferior to current routines. All Nordic Upper Gastrointestinal Cancer centers were invited to participate in this open-label pragmatic randomized controlled trial (RCT). Inclusion criteria include resection for locally advanced esophageal cancer with gastric tube reconstruction. A pretrial survey was undertaken and was the foundation for a consensus process resulting in the Kinetic trial, an RCT allocating patients to either no use of a NG tube (intervention) or 5 days of postoperative NG tube use (control) with anastomotic leakage as primary endpoint. Secondary endpoints include pulmonary complications, overall complications, length of stay, health related quality of life. A sample size of 450 patients is planned (Kinetic trial: https://www.isrctn.com/ISRCTN39935085). Thirteen Nordic centers with a combined catchment area of 17 million inhabitants have entered the trial and ethical approval was granted in Sweden, Norway, Finland, and Denmark. All centers routinely use NG tube and all but one center use total or hybrid minimally invasive-surgical approach. Inclusion began in January 2022 and the first annual safety board assessment has deemed the trial safe and recommended continuation. We have launched the first adequately powered multi-center pragmatic controlled randomized clinical trial regarding NG tube use after esophagectomy with gastric conduit reconstruction.

Factors affecting consonant production accuracy in children with cochlear implants: Expressive vocabulary and maternal education.

BACKGROUND: Despite the ability of cochlear implants (CIs) to provide children with access to speech, there is considerable variability in spoken language outcomes. Research aimed at identifying factors influencing speech production accuracy is needed. AIMS: To characterize the consonant production accuracy of children with cochlear implants (CWCI) and an age-matched group of children with typical hearing (CWTH) and to explore several factors that potentially affect the ability of both groups to accurately produce consonants. METHODS & PROCEDURES: We administered the Bankson-Bernthal Test of Phonology (BBTOP) to a group of 25 CWCI (mean age = 4;9, SD = 1;6, range = 3;2-8;5) implanted prior to 30 months of age with a mean duration of implant usage of 3;6 and an age-matched group of 25 CWTH (mean age = 5;0, SD = 1;6, range = 3;1-8;6). The recorded results were transcribed, and the accuracy of the target consonants was determined. Expressive vocabulary size estimates were obtained from a language sample using the number of different words (NDW). A parent questionnaire provided information about maternal education, duration of CIs experience and other demographic characteristics of each child. OUTCOMES & RESULTS: The CWCI group demonstrated some similarities to, and some differences from, their hearing peers. The CWCI demonstrated poorer consonant production accuracy overall and in various phonetic categories and word positions. However, both groups produced initial consonants more accurately than final consonants. Whilst CWCI had poorer production accuracy than CWTH for all phonetic categories (stops, nasals, fricatives, affricates, liquids and glides and consonant clusters), both groups exhibited similar error patterns across categories. For CWCI, the factors most related to consonant production accuracy when considered individually were expressive vocabulary size, followed by duration of CI experience, chronological age, maternal education and gender. The combination of maternal education and vocabulary size resulted in the best model of consonant production accuracy for this group. For the CWTH, chronological age followed by vocabulary size were most related to consonant production accuracy. No combination of factors yielded an improved model for the CWTH. CONCLUSIONS & IMPLICATIONS: Whilst group differences in production accuracy between the CWCI and CWTH were found, the pattern of errors was similar for the two groups of children, suggesting that the children are at earlier stages of overall consonant production development. Although duration of CI experience was a significant covariate in a single-variable model of consonant production accuracy for CWCI, the best multivariate model of consonant production accuracy for these children was based on the combination of expressive vocabulary size and maternal education. WHAT THIS PAPER ADDS: What is already known on the subject Research has shown that a range of factors is associated with consonant production accuracy by CWCIs, including factors such as the age at implant, duration of implant use, gender, other language skills and maternal education. Despite numerous studies that have examined speech sound production in these children, most have explored a limited number of factors that might explain the variability in scores obtained. Research that examines the potential role of a range of child-related and environmental factors in the same children is needed to determine the predictive role of these factors in speech production outcomes. What this paper adds to the existing knowledge Whilst the consonant production accuracy was lower for the CWCIs than for their typically hearing peers, there were some similarities suggesting that these children are experiencing similar, but delayed, acquisition of consonant production skills to that of their hearing peers. Whilst several factors are predictive of consonant production accuracy in children with implants, vocabulary diversity and maternal education, an indirect measure of socio-economic status, were the best combined predictors of consonant production accuracy. What are the potential or actual clinical implications of this work? Understanding the factors that shape individual differences in CWCI speech production is important for effective clinical decision-making and intervention planning. The present findings point to two potentially important factors related to speech sound production beyond the duration of robust hearing in CWCI, namely, a lexical diversity and maternal education. This suggests that intervention is likely most efficient that addresses both vocabulary development and speech sound development together. The current findings further suggest the importance of parental involvement and commitment to spoken language development and the importance of receiving early and consistent intervention aimed both at skill development and parental efficacy.

Benefits of EUS-guided gastroenterostomy over surgical gastrojejunostomy in the palliation of malignant gastric outlet obstruction: a large multicenter experience.

BACKGROUND AND AIMS: Palliation of malignant gastric outlet obstruction (mGOO) allows resumption of peroral intake. Although surgical gastrojejunostomy (SGJ) provides durable relief, it may be associated with a higher morbidity, interfere with chemotherapy, and require an optimum nutritional status. EUS-guided gastroenterostomy (EUS-GE) has emerged as a minimally invasive alternative. We aimed to conduct the largest comparative series to date between EUS-GE and SGJ for mGOO. METHODS: This multicenter retrospective study included consecutive patients undergoing SGJ or EUS-GE at 6 centers. Primary outcomes included time to resumption of oral intake, length of stay (LOS), and mortality. Secondary outcomes included technical and clinical success, reintervention rates, adverse events (AEs), and resumption of chemotherapy. RESULTS: A total of 310 patients were included (EUS-GE, n = 187; SGJ, n = 123). EUS-GE exhibited significantly lower time to resumption of oral intake (1.40 vs 4.06 days, P < .001), at lower albumin levels (2.95 vs 3.33 g/dL, P < .001), and a shorter LOS (5.31 vs 8.54 days, P < .001) compared with SGJ; there was no difference in mortality (48.1% vs 50.4%, P = .78). Technical (97.9% and 100%) and clinical (94.1% vs 94.3%) success was similar in the EUS-GE and SGJ groups, respectively. EUS-GE had lower rates of AEs (13.4% vs 33.3%, P < .001) but higher reintervention rates (15.5% vs 1.63%, P < .001). EUS-GE patients exhibited significantly lower interval time to resumption of chemotherapy (16.6 vs 37.8 days, P < .001). Outcomes between the EUS-GE and laparoscopic (n = 46) surgical approach showed that EUS-GE had shorter interval time to initiation/resumption of oral intake (3.49 vs 1.46 days, P < .001), decreased LOS (9 vs 5.31 days, P < .001), and a lower rate of AEs (11.9% vs 17.9%, P = .003). CONCLUSIONS: This is the largest study to date showing that EUS-GE can be performed among nutritionally deficient patients without affecting the technical and clinical success compared with SGJ. EUS-GE is associated with fewer AEs while allowing earlier resumption of diet and chemotherapy.

Effectiveness and Safety of EUS Rendezvous After Failed Biliary Cannulation With ERCP: A Systematic Review and Proportion Meta-analysis.

BACKGROUND: Endoscopic ultrasound-guided rendezvous (EUS-RV) endoscopic retrograde cholangiopancreatography (ERCP) is an alternative to interventional radiology-guided rendezvous ERCP in patients who failed biliary cannulation with conventional ERCP. However, there is significant variation in reported rates of success and adverse events associated with EUS-RV-assisted ERCP. We performed a systematic review and a proportion meta-analysis to reliably assess the effectiveness and safety of the EUS-RV-assisted ERCP. MATERIALS AND METHODS: We conducted a comprehensive search of multiple electronic databases and conference proceedings (from inception through August 2020) to identify studies reporting EUS-RV-assisted ERCP in patients who failed biliary cannulation with conventional ERCP techniques. Using the random-effects model described by DerSimonian and Laird, we calculated the pooled rates of technical success, clinical success, and adverse events of EUS-RV-assisted ERCP. RESULTS: Twelve studies reporting a total of 342 patients were included in the meta-analysis. The pooled rate of technical success (12 studies reporting a total of 342 patients) was 86.1% [95% confidence interval (CI): 78.4-91.3]. The pooled rate of clinical success (4 studies reporting a total of 94 patients) was 80.8% (95% CI: 64.1-90.8). The pooled rate of overall adverse events (12 studies; 42 events in 342 patients) was 14% (95% CI: 10.5-18.4). Low to moderate heterogeneity was noted in the analyses. CONCLUSIONS: EUS-RV-assisted ERCP appears to be effective and safe in patients who failed biliary cannulation with conventional ERCP. Given the risk of adverse events, it should be performed in centers with expertise in therapeutic endoscopic ultrasound.

Antibiotic treatment of bacterial vaginosis to prevent preterm delivery: Systematic review and individual participant data meta-analysis.

BACKGROUND: Bacterial vaginosis (BV) increases preterm delivery (PTD) risk, but treatment trials showed mixed results in preventing PTD. OBJECTIVES: Determine, using individual participant data (IPD), whether BV treatment during pregnancy reduced PTD or prolonged time-to-delivery. DATA SOURCES: Cochrane Systematic Review (2013), MEDLINE, EMBASE, journal searches, and searches (January 2013-September 2022) ("bacterial vaginosis AND pregnancy") of (i) clinicaltrials.gov; (ii) Cochrane Central Register of Controlled Trials; (iii) World Health Organization International Clinical Trials Registry Platform Portal; and (iv) Web of Science ("bacterial vaginosis"). STUDY SELECTION AND DATA EXTRACTION: Studies randomising asymptomatic pregnant individuals with BV to antibiotics or control, measuring delivery gestation. Extraction was from original data files. Bias risk was assessed using the Cochrane tool. Analysis used "one-step" logistic and Cox random effect models, adjusting gestation at randomisation and PTD history; heterogeneity by I2 . Subgroup analysis tested interactions with treatment. In sensitivity analyses, studies not providing IPD were incorporated by "multiple random-donor hot-deck" imputation, using IPD studies as donors. RESULTS: There were 121 references (96 studies) with 23 eligible trials (11,979 participants); 13 studies (6915 participants) provided IPD; 12 (6115) were incorporated. Results from 9 (4887 participants) not providing IPD were imputed. Odds ratios for PTD for metronidazole and clindamycin versus placebo were 1.00 (95% CI 0.84, 1.17), I2  = 62%, and 0.59 (95% CI 0.42, 0.82), I2  = 0 before; and 0.95 (95% CI 0.81, 1.11), I2  = 59%, and 0.90 (95% CI: 0.72, 1.12), I2  = 0, after imputation. Time-to-delivery did not differ from null with either treatment. Including imputed IPD, there was no evidence that either drug was more effective when administered earlier, or among those with a PTD history. CONCLUSIONS: Clindamycin, but not metronidazole, was beneficial in studies providing IPD, but after imputing data from missing IPD studies, treatment of BV during pregnancy did not reduce PTD, nor prolong pregnancy, in any subgroup or when started earlier in gestation.

A unidirectional mapping of ICD-8 to ICD-10 codes, for harmonized longitudinal analysis of diseases.

Periodic revisions of the international classification of diseases (ICD) ensure that the classification reflects new practices and knowledge; however, this complicates retrospective research as diagnoses are coded in different versions. For longitudinal disease trajectory studies, a crosswalk is an essential tool and a comprehensive mapping between ICD-8 and ICD-10 has until now been lacking. In this study, we map all ICD-8 morbidity codes to ICD-10 in the expanded Danish ICD version. We mapped ICD-8 codes to ICD-10, using a many-to-one system inspired by general equivalence mappings such that each ICD-8 code maps to a single ICD-10 code. Each ICD-8 code was manually and unidirectionally mapped to a single ICD-10 code based on medical setting and context. Each match was assigned a score (1 of 4 levels) reflecting the quality of the match and, if applicable, a "flag" signalling choices made in the mapping. We provide the first complete mapping of the 8596 ICD-8 morbidity codes to ICD-10 codes. All Danish ICD-8 codes representing diseases were mapped and 5106 (59.4%) achieved the highest consistency score. Only 334 (3.9%) of the ICD-8 codes received the lowest mapping consistency score. The mapping provides a scaffold for translation of ICD-8 to ICD-10, which enable longitudinal disease studies back to and 1969 in Denmark and to 1965 internationally with further adaption.

Safety and clinical outcomes of early dual modality drainage (< 28 days) compared to later drainage of pancreatic necrotic fluid collections: a propensity score-matched study.

BACKGROUND: Necrotizing pancreatitis can be complicated by Necrotic Fluid Collections (NFC). Guidelines recommend waiting for 4 weeks from the onset of acute pancreatitis (AP) before considering endoscopic drainage. We aimed to compare outcomes and safety in patients undergoing early versus late drainage of NFC. METHODS: We performed a retrospective review of all patients who underwent Dual Modality Drainage (DMD) [combined endoscopic and percutaneous drainage] for NFC from January 2007 to December 2020. Patients were stratified into the "early" group (DMD < 28 days from AP onset) and were matched to "late" (DMD ≥ 28 days) drainage group using propensity- core-matching. Primary outcomes of interest were technical success and adverse events. Secondary outcomes included clinical success, late complication rates, and mortality. RESULTS: We identified 278 patients who underwent DMD for NFC. Thirty-nine belonged to the early group and were matched to 174 patients from the late group. Technical success was similar in both early and late groups (97.4% vs 99.4%: P = 0.244) as were the procedural and early post-procedural (< 14 days) adverse events rates (23.1% vs 27.6%: P = 0.565). Clinical success (92.3% vs 93.1%; P = 0.861) and late complication rates (23.1% vs 31.6%; P = 0.294) were similar. There were 2 deaths (5.7%) in the early vs. 9 (5.2%) in the late group, P = 0.991. CONCLUSIONS: When performed in a tertiary care center with expertise in therapeutic endoscopic ultrasound, early drainage of NFC appears to be feasible and safe. Further studies are needed to validate our results.

Learning Curves of Ivor Lewis Totally Minimally Invasive Esophagectomy by Hospital and Surgeon Characteristics: A Retrospective Multinational Cohort Study.

OBJECTIVE: To describe the pooled learning curves of Ivor Lewis totally minimally invasive esophagectomy (TMIE) in hospitals stratified by predefined hospital- and surgeon-related factors. BACKGROUND: Ivor Lewis (TMIE is known to have a long learning curve which is associated with considerable learning associated morbidity. It is unknown whether hospital and surgeon characteristics are associated with more efficient learning. METHODS: A retrospective analysis of prospectively collected data of consecutive Ivor Lewis TMIE patients in 14 European hospitals was performed. Outcome parameters used as proxy for efficient learning were learning curve length, learning associated morbidity, and the plateau level regarding anastomotic leakage and textbook outcome. Pooled incidences were plotted for the factor-based subgroups using generalized additive models and 2-phase models. Casemix predicted outcomes were plotted and compared with observed outcomes. The investigated factors included annual volume, TMIE experience, clinic visits, courses and fellowships followed, and proctor supervision. RESULTS: This study included 2121 patients. The length of the learning curve was shorter for centers with an annual volume >50 compared to centers with an annual volume <50. Analysis with an annual volume cut-off of 30 cases showed similar but less pronounced results. No outcomes suggesting more efficient learning were found for longer experience as consultant, visiting an expert clinic, completing a minimally invasive esophagectomy fellowship or implementation under proctor supervision. CONCLUSIONS: More efficient learning was observed in centers with higher annual volume. Visiting an expert clinic, completing a fellowship, or implementation under a proctor's supervision were not associated with more efficient learning.

Infliximab Is Not Associated With a General Long-Term Weight Gain in Patients With Inflammatory Bowel Disease: A Nationwide Study.

INTRODUCTION: Patients with Crohn's disease (CD) and ulcerative colitis (UC) may lose weight during periods of active disease and may gain weight when inflammation heals. Studies have hypothesized an association between antitumor necrosis factor-alpha (anti-TNF-α) and unintended weight gain during maintenance therapy, and this association has not been previously clarified. METHODS: In a nationwide observational study based on Danish national health registries, we included patients who initiated therapy with infliximab and followed changes in weight during induction therapy (0-90 days) and maintenance therapy (91-270 days). The association between the use of infliximab and weight gain was analyzed by a multilevel mixed-effects linear regression model. RESULTS: Among 851 patients with CD and UC who initiated infliximab therapy, long-term weight gain was not observed during maintenance therapy in most of the patients. Women with CD who were underweight at the initiation of therapy had an average weight gain of 7.5 kg. Men and women with CD and UC with normal or increased body mass index had an average weight gain of <2 kg during maintenance therapy. Underweight men with CD and UC gained 2.9 kg (95% confidence interval 2.1-3.6) and 2.9 kg (95% confidence interval 1.9-3.9), respectively, in the first 90 days, although neither group had statistically significant weight gain in the maintenance period. Less than 3% of the patients had weight gain greater than 10% of their baseline body weight during the study period. DISCUSSION: Weight gain among patients treated with anti-TNF-α therapies is unlikely to be due to an effect from anti-TNF-α therapy.

Smoking in pregnancy is associated with increased adiposity and retinal arteriolar wall-to-lumen ratio in adolescence: The Copenhagen Child Cohort Study 2000.

PURPOSE: To investigate the association between prenatal exposures and anthropometric data and cardiovascular risk factors including retinal arteriolar wall-to-lumen ratio in adolescence. METHODS: This longitudinal observational study included all 1445 adolescents from the Copenhagen Child Cohort 2000 who attended the 2016-2017 examination. Outcome measures included retinal arteriolar wall-to-lumen ratio, height, body mass index, waist-to-hip ratio, body composition measured by bioimpedance, and blood pressure. Information on prenatal exposures (birth weight, gestational age, maternal smoking during pregnancy) as well as sex, parental age, household income and parental educational levels were obtained from national registries. Associations between exposures and outcome measures were analyzed using general linear models. RESULTS: Maternal smoking during pregnancy was associated with a higher retinal arteriolar wall-to-lumen ratio (0.004 or 1.9%, P = 0.009) at age 16/17 years, an association driven exclusively by the female participants (0.008 or 3.7%, P < 0.0001). Maternal smoking during pregnancy was also associated to higher body-mass index (1.43 kg/m2, P < 0.0001), waist-to-hip ratio (0.02, P < 0.0001) and fat mass index (0.93 kg/m2, P < 0.0001). Birth weight, gestational age, and parental age had no detectable impact on retinal arteriolar wall-to-lumen ratios. CONCLUSION: Prenatal exposure to tobacco smoking is associated with a higher risk of obesity and, predominantly in girls, to a greater retinal arteriolar wall thickness, which suggests that maternal smoking may induce an unfavorable cardiovascular and metabolic risk profile in the child.

Thermodynamic, kinetic, and mechanistic studies of the thermal guanidine metathesis reaction.

We describe studies of the thermal guanidine metathesis (TGM) reaction, a reversible transformation that results in exchange of N-substituents of the guanidine functional group. By comparing the effects of discrete structural variations, we find that steric congestion is an important factor in determining both the equilibrium guanidine composition and the reaction kinetics. The alkyl versus aryl nature of N-substitution also plays an essential role in the reaction rate, up to the point that minimal TGM reactivity is observed when the guanidine contains wholly alkyl substituents. Furthermore, we demonstrate that TGM occurs under thermodynamic control and present evidence that it proceeds by a dissociative mechanism, supported by direct observation of a carbodiimide intermediate.

Physical activity measured by accelerometry in paediatric and young adult patients with inflammatory bowel disease.

OBJECTIVES: Physical activity in paediatric and young adult patients suffering from inflammatory bowel disease (IBD) may play an important role in the overall health status. However, physical activity in these patients has not been reported using objective methods. We aimed to describe accelerometry-measured physical activity levels in paediatric and young adult IBD patients with either ulcerative colitis (UC) or Crohn's disease (CD). METHODS: We recruited Danish patients with IBD aged 10-20 years in clinical remission and with a faecal calprotectin below 200 µg/mg. Physical activity was assessed using tri-axial wrist accelerometry over seven days and quantified using the activity-related acceleration derived as the conventional Euclidian Norm Minus One (ENMO) metric expressed in milli-gravity units (mg). Time spent in Moderate-to-Vigorous Physical Activity (MVPA) was classified as ENMO > 210 mg in 5 s epoch resolution (unbouted). RESULTS: We included 61 patients with a median age of 17 years [Inter Quartile Range, IQR 14-19]. The total volume of activity expressed as average acceleration (ENMO) per day was 31.5 mg (95% CI 29.1-33.9). Time spent in unbouted MVPA was 32 min per day (95% CI 26-37). There was no significant difference in activity volume between patients with UC to patients with CD, the adjusted linear regression coefficient was - 1.7 mg (95% CI -6.2-2.7). Activity volume was higher for males (36.2 mg, 95% CI 31.9-40.5) than for females (27.8 mg, 95% CI 25.6-30.0), and younger patients were more active than older patients; Activity volume in 10-13 year olds was 37.2 mg (95% CI 28.6-45.7), whereas it was 28.5 mg (95% CI 25.2-31.7) for those aged 18-20 years. CONCLUSIONS: We collected tri-axial accelerometry in young patients with IBD in clinical remission, and described their level of physical activity by the conventional ENMO measure. We found no statistically significant difference in patients with UC compared to patients with CD. The volume of physical activity was higher in males compared to females, and inversely associated with age.

Biliary Sphincterotomy Alone versus Biliary Stent with or without Biliary Sphincterotomy for the Management of Post-Cholecystectomy Bile Leak: A Systematic Review and Meta-Analysis.

BACKGROUND: Endoscopic therapy with endoscopic retrograde cholangiopancreatography is considered the first-line treatment in the management of post-cholecystectomy bile leak (PCBL). Currently, there is no consensus on the most effective endoscopic intervention for PCBL. Hence, we performed a systematic review and meta-analysis to compare the effectiveness and safety of the two interventional groups (biliary sphincterotomy [BS] alone vs. biliary stent ± BS) in management of PCBL. METHODS: We conducted a comprehensive search of multiple electronic databases and conference proceedings (from inception through January 2021). The primary outcome was to compare the pooled rate of clinical success between the 2 groups. The secondary outcome was to estimate the pooled rate of adverse events. RESULTS: The pooled rate of clinical success with BS alone (5 studies, 299 patients) was 88% (95% confidence interval (CI): 84-92%, I2: 0%) and for biliary stent ± BS (5 studies, 864 patients) was 97% (CI: 93-100%, I2: 79%). The rate of clinical success in biliary stent ± BS group was significantly higher than BS alone group (OR: 3.91 95% CI: 2.29-6.69, p < 0.001, I2: 13%). The rate of adverse events was numerically lower in biliary stent ± BS group compared to BS alone (3 studies; OR: 0.65 95% CI: 0.41-1.03, p = 0.07) without statistical significance. Low heterogeneity was noted in the analysis. CONCLUSIONS: Biliary stent ± BS is more effective in endoscopic management of PCBL compared to BS alone. This may be related to inter-endoscopist variation in completeness of sphincterotomy and post-sphincterotomy edema, which can influence the preferential trans-papillary flow of bile.

Usefulness of Fluoroscopy for Endoscopic Balloon Dilation of Crohn's Disease-Related Strictures.

BACKGROUND: Fluoroscopy is often used for endoscopic balloon dilation (EBD) of Crohn's disease (CD)-related strictures. However, its benefit remains unclear. AIMS: To compare EBD with (EBDF) and without (EBDNF) fluoroscopic guidance in CD patients with strictures. METHODS: Single-center, nested, case-control retrospective study of EBD for CD-related strictures. Technical and clinical success and safety outcomes were compared between EBDF and EBDNF. RESULTS: A total of 122 strictures in 114 CD patients who underwent EBD from 2010 to 2018 at a single institution were reviewed (44 patients EBDF vs. 70 EBDNF). Esophagogastroduodenoscopy was the approach in 8 strictures, colonoscopy in 86, and deep enteroscopy in 28. There were no significant differences in the rates of technical and clinical success, need for repeat dilation and surgery between the two groups, although the mean maximal endoscopic balloon diameter was larger in the EBDNF group (17.1 ± 1.9 vs. 14.1 ± 2.5; p < 0.001). There was one perforation in EBDF and no serious complications in EBDNF. In multivariate analysis, balloon size < 15 mm (odds ratio [OR] 6.388; 95% CI 1.96-20.79; p = 0.002) and multiple strictures (OR 3.897; 95% CI 1.09-14.01; p = 0.037) were associated with repeat EBD, and age < 50 years (OR 7.178; 95% CI 1.38-37.44; p = 0.019) and small bowel (vs. colon) location (OR 7.525; 95% CI 1.51-37.47; p = 0.014) were associated with the need for surgery after EBD. CONCLUSIONS: EBD for CD-related strictures can be performed safely and effectively without fluoroscopic guidance. Balloon size, patient age, stricture location, and multiplicity are associated with clinical success and avoidance of surgery.

Effectiveness and Safety of Lumen-Apposing Metal Stents in Endoscopic Interventions for Off-Label Indications.

BACKGROUND: Although released only for drainage of pseudocyst and walled-off necrosis (WON) with ≤ 30% solid debris, the utilization of lumen-apposing metal stent (LAMS) in "real-world" practice has deviated from approved indications. We evaluated the contemporary use of LAMS and associated clinical, procedural outcomes in the setting of a tertiary referral center in the USA. METHODS: Data from 303 consecutive patients who underwent LAMS placement were analyzed. Outcomes included technical and clinical success rates and adverse events. RESULTS: Of 303 patients, 190 (62.7%) received LAMS for off-label indications. The latter included gallbladder drainage (n = 56, 18.5%), gastroenterostomy (n = 52, 17.2%), treatment of gastrointestinal strictures (n = 37, 12.2%), biliary drainage (n = 20, 6.6%), temporary gastric access for endoscopy (n = 13, 4.3%), symptomatic WON with > 30% solid debris (n = 8, 2.6%), and miscellaneous (n = 4, 1.3%). Technical success rates in the on- and off-label arm were 98.2% and 95.8%, respectively (P = .331; 95% CI 0.08 to 1.96). Clinical success rates in the on- and off-label arm were 89.4% and 83.2%, respectively (P = .137; 95% CI 0.28 to 1.19). The rate of adverse events was 20.5% (n = 39) in the off-label arm and 16.8% (n = 19) in the on-label arm (P = .242; 95% CI 0.69 to 2.34). CONCLUSION: Off-label use of LAMS out-numbered on-label use in our practice. The safety profile between the groups was similar and with the exception of refractory stricture treatment, efficacy was comparable.

Heritability and Risk Factors of Incident Small and Large Drusen in the Copenhagen Twin Cohort Eye Study: A 20-Year Follow-Up.

INTRODUCTION: The transition from a normal fundus to one with early drusen (≥20 small hard drusen) to age-related macular degeneration (AMD) in the form of drusen ≥63 µm in diameter is of interest, because small hard drusen may be precursors of large drusen. Study of AMD precursor lesions may provide valuable insight into factors that initiate AMD. Here, the progression of drusen was studied over an interval of 20 years in a population-based twin cohort. METHODS: Single-center, 20-year follow-up of 138 twins include biometry, fundus optical coherence tomography, and fundus photography. Macular characteristics were hierarchically classified as (per eye) (1) <20 small hard drusen, (2) ≥20 small hard drusen, (3) drusen ≥63 µm, or (4) ≥20 small hard drusen combined with drusen ≥63 µm. Additive and dominant genetic effects as well as shared and nonshared environmental effects were analyzed in a bivariate biprobit model with a classic liability-threshold approach and polygenic modeling with random effects. RESULTS: Median participant age was 59 (range 41-66) years. Of 25 (18%) cases of incident macular drusen, 7 had ≥20 small hard drusen, and 18 had drusen ≥63 µm at follow-up, whereas no participant had developed both traits simultaneously. Smoking was associated with incident ≥20 small hard drusen (p = 0.04) and incident drusen ≥63 µm (p = 0.003). Having ≥20 small hard drusen at baseline was associated with incident drusen ≥63 µm at follow-up (p = 0.02). Development of drusen ≥63 µm was attributable to 49% genetic effects and 51% environmental effects. CONCLUSION: The risk of progressing from 0 to 19 small hard macular drusen per eye to having ≥20 small hard drusen or drusen ≥63 µm at follow-up was associated with smoking and genetic predisposition. Having ≥20 small hard drusen in the absence of drusen ≥63 µm at baseline was associated with incident drusen ≥63 µm when examined 20 years later. The study confirms that small hard macular drusen is a forewarning of AMD and that progression to AMD may be hindered by avoidance of smoking.

Prevalence of Macular Microcystoid Lacunae in Autosomal Dominant Optic Atrophy Assessed With Adaptive Optics.

BACKGROUND: To assess the prevalence of macular microcystoid lacunae in patients with autosomal dominant optic atrophy (ADOA) and its association with visual function and inner retinal morphology. METHODS: The study included 140 participants with ADOA, with a mean age of 44 (SD ±19, range 7-82) years. Study participants with a genetically verified sequence variant in the OPA1 gene were examined with best-corrected visual acuity, contrast sensitivity, optical coherence tomography (Spectralis, Heidelberg) and adaptive optics fundus photography (rtx1, Imagine Eyes). Optically empty microcystoid spaces in the ganglion cell layer and inner plexiform layer were mapped by inspection of the 2 sets of images. Data were analyzed with a mixed model adjusted for age and sex with family and individual as random effect. RESULTS: Microcystoid lacunae were present in 32 of 140 participants (23%) including 18 males and 14 females. Microcystoid lacunae were associated with younger age ( P = 0.0503) and a smaller nerve fiber layer volume ( P = 0.035). No association was found between presence of microcystoid lacunae and visual acuity ( P = 0.2), contrast sensitivity ( P = 0.8), axial length ( P = 0.7), or ganglion cell layer volume ( P = 0.2). The analysis showed moderately reduced visual acuity in patients with microcystoid lacunae. Normal and severely impaired visual function were seen only in participants without microcystoid lacunae. CONCLUSION: In ADOA, macular microcystoid lacunae were found in 23% of the study participants and tended to be present in younger participants with moderate visual acuity reduction and a smaller nerve fiber layer volume. Further studies are needed to investigate whether cavities left by dead ganglion cells are predictors of decrease in visual function.

Nurse-Administered Propofol Continuous Infusion Sedation for Gastrointestinal Endoscopy in Patients Who Are Difficult to Sedate.

BACKGROUND & AIMS: Patients who chronically use alcohol, marijuana, or opioids, or suffer from post-traumatic stress disorder (PTSD), can be difficult to sedate with midazolam and fentanyl, and often are referred for monitored anesthesia care during endoscopy. Nurse-administered propofol continuous infusion sedation (NAPCIS), which confers the benefit of propofol-based sedation without the added expense of anesthesia, is effective and safe for sedation of healthy patients. We investigated whether NAPCIS also is effective for patients who are difficult to sedate. METHODS: We performed a retrospective study of patients who underwent upper endoscopy or colonoscopy with NAPCIS at a single center from January 2018 through April 2018. We reviewed records from patients who were heavy users of alcohol (n = 105), daily users of marijuana (n = 267) or opioids (n = 178), had a diagnosis of PTSD (n = 91), or were none of these (controls, n = 786). We compared mean fentanyl and propofol doses (adjusted for body weight), procedure and recovery times, procedure success rates, and adverse events. RESULTS: Compared with the controls, the marijuana group required higher mean adjusted sedative doses for colonoscopies (0.6 vs 0.4 mcg/kg fentanyl and 5.0 vs 4.7 mg/kg propofol; P ≤ .025 for both) and upper endoscopies (0.8 vs 0.3 mcg/kg fentanyl and 3.7 vs 3.2 mg/kg propofol; P ≤ .021 for both), the PTSD group required a higher dose of fentanyl for colonoscopies (0.6 vs 0.4 mcg/kg; P = .009), and the alcohol group required a higher dose of fentanyl for upper endoscopies (0.7 vs 0.3 mcg/kg; P < .001). Procedure success rates were high (95.1%-100%) and did not differ significantly between the difficult-to-sedate groups and controls; mean procedure times (7.0-9.0 minutes for upper endoscopies, 21.1-22.9 minutes for colonoscopies) and recovery times (22.5-29.6 minutes) also were similar among groups. Upper endoscopies were associated with lower sedative doses and shorter procedure and recovery times than colonoscopies. Sedation-related adverse events were rare in all groups (only 26 cases total), and there were no serious complications or deaths. CONCLUSIONS: NAPCIS seems to be a safe and effective means of providing sedation for endoscopy to patients who may be difficult to sedate owing to alcohol, marijuana, or opioid use, or PTSD.

Nurse-Administered Propofol Continuous Infusion Sedation: A New Paradigm for Gastrointestinal Procedural Sedation.

INTRODUCTION: Nurse-Administered Propofol Continuous Infusion Sedation (NAPCIS) is a new nonanesthesia propofol delivery method for gastrointestinal endoscopy. NAPCIS is adopted from the computer-assisted propofol sedation (CAPS) protocol. We evaluated the effectiveness, efficiency, and safety of NAPCIS in low-risk subjects. METHODS: Between December 2016 and July 2017, patients who underwent esophagogastroduodenoscopy or colonoscopy with NAPCIS at our center were compared against 2 historical control groups of similar patients who had undergone procedures with CAPS or midazolam and fentanyl (MF) sedation. RESULTS: The mean age of the NAPCIS cohort (N = 3,331) was 55.2 years (45.8% male) for 945 esophagogastroduodenoscopies and 57.8 years (48.7% male) for 2,386 colonoscopies. The procedural success rates with NAPCIS were high (99.1%-99.2%) and similar to those seen in 3,603 CAPS (98.8%-99.0%) and 3,809 MF (99.0%-99.3%) controls. NAPCIS recovery times were shorter than both CAPS and MF (24.8 vs 31.7 and 52.4 minutes, respectively; P < 0.001). On arrival at the recovery unit, 86.6% of NAPCIS subjects were recorded as "Awake" compared with 82.8% of CAPS and 40.8% of MF controls (P < 0.001). Validated clinician and patient satisfaction scores were generally higher for NAPCIS compared with CAPS and MF subjects. For NAPCIS, there were only 4 cases of oxygen desaturation requiring transient mask ventilation and no serious sedation-related complications. These low complication rates were similar to those seen with CAPS (8 cases of mask ventilation) and MF (3 cases). DISCUSSION: NAPCIS seems to be a safe, effective, and efficient means of providing moderate sedation for upper endoscopy and colonoscopy in low-risk patients.

Outcome of COVID-19 in hospitalized patients with chronic inflammatory diseases. A population based national register study in Denmark.

OBJECTIVE: COVID-19 has substantial morbidity and mortality. We studied whether hospitalized patients with COVID-19 and chronic inflammatory diseases experienced worse outcomes compared to patients hospitalized with COVID-19 without chronic inflammatory diseases. METHODS: Danish nationwide registers were used to establish a cohort of hospitalized patients with COVID-19 and inflammatory bowel diseases (IBD), rheumatoid arthritis (RA), spondyloarthropathy (SpA), or psoriatic arthritis (PsA) (exposed), and a control cohort without these diseases (unexposed) between March 1, 2020, and October 31, 2020. We compared median length of hospital stay, used median regression models to estimate crude and adjusted differences. When estimating crude and adjusted odds ratio (OR) for continuous positive airway pressure (CPAP) and mechanical ventilation, in-hospital death, 14-day and 30-day mortality, we used logistic regression models. RESULTS: We identified 132 patients with COVID-19 and IBD, RA, SpA, or PsA, and 2811 unexposed admitted to hospital with COVID-19. There were no differences between exposed and unexposed regarding length of hospital stay (6.8 days vs. 5.5 days), need for mechanical ventilation (7.6% vs. 9.4%), or CPAP (11.4% vs. 8.8%). Adjusted OR for in-hospital death was 0.71 (95% CI 0.42-1.22), death after 14-days 0.70 (95% CI 0.42-1.16), and death after 30-days 0.68 (95% CI 0.41-1.13). CONCLUSION: Hospitalized patients with COVID-19 and chronic inflammatory diseases did not have statistically significant increased length of hospital stay, had same need for mechanical ventilation, and CPAP. Mortality was similar in hospitalized patients with COVID-19 and chronic inflammatory diseases, compared to patients hospitalized with COVID-19 and no chronic inflammatory diseases.