Locally narrow droplet size distributions are ubiquitous in stratocumulus clouds.

Marine stratocumulus clouds are the "global reflectors," sharply contrasting with the underlying dark ocean surface and exerting a net cooling on Earth's climate. The magnitude of this cooling remains uncertain in part owing to the averaged representation of microphysical processes, such as the droplet-to-drizzle transition in global climate models (GCMs). Current GCMs parameterize cloud droplet size distributions as broad, cloud-averaged gammas. Using digital holographic measurements of discrete stratocumulus cloud volumes, we found cloud droplet size distributions to be narrower at the centimeter scale, never resembling the cloud average. These local distributions tended to form pockets of similar-looking cloud regions, each characterized by a size distribution shape that is diluted to varying degrees. These observations open the way for new modeling representations of microphysical processes.

Central serous chorioretinopathy: An evidence-based treatment guideline.

Central serous chorioretinopathy (CSC) is a relatively common disease that causes vision loss due to macular subretinal fluid leakage and it is often associated with reduced vision-related quality of life. In CSC, the leakage of subretinal fluid through defects in the retinal pigment epithelial layer's outer blood-retina barrier appears to occur secondary to choroidal abnormalities and dysfunction. The treatment of CSC is currently the subject of controversy, although recent data obtained from several large randomized controlled trials provide a wealth of new information that can be used to establish a treatment algorithm. Here, we provide a comprehensive overview of our current understanding regarding the pathogenesis of CSC, current therapeutic strategies, and an evidence-based treatment guideline for CSC. In acute CSC, treatment can often be deferred for up to 3-4 months after diagnosis; however, early treatment with either half-dose or half-fluence photodynamic therapy (PDT) with the photosensitive dye verteporfin may be beneficial in selected cases. In chronic CSC, half-dose or half-fluence PDT, which targets the abnormal choroid, should be considered the preferred treatment. If PDT is unavailable, chronic CSC with focal, non-central leakage on angiography may be treated using conventional laser photocoagulation. CSC with concurrent macular neovascularization should be treated with half-dose/half-fluence PDT and/or intravitreal injections of an anti-vascular endothelial growth factor compound. Given the current shortage of verteporfin and the paucity of evidence supporting the efficacy of other treatment options, future studies-ideally, well-designed randomized controlled trials-are needed in order to evaluate new treatment options for CSC.

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.

Longitudinal Measurements of Blood Biomarkers in Patients with Crohn's Disease or Ulcerative Colitis Treated with Infliximab: Only the Latest Values in the Induction Period Predict Treatment Failure.

Background: Few studies have incorporated longitudinal assessments or used combinations of blood biomarkers as predictors of loss of response to biologic therapy for patients with Crohn's disease (CD) or ulcerative colitis (UC). Methods: This is a population-based cohort study comprising Danish patients with CD or UC from 2008 to 2018. We used logistic regression to analyze whether levels and changes in levels of C-reactive protein (CRP), serum albumin, and hemoglobin, routinely measured during a 14-week infliximab induction period, predicted a change to another biologic medication or cessation of biologic therapy. Results: During the induction period, 2883 (1626 CD, 1257 UC) patients had 12,730, 12,040, and 13,538 specimens with CRP, serum albumin, and hemoglobin, respectively. In all, 284 patients (9.9%) switched to another biologic medication, and 139 (4.8%) ceased biologic therapy in the follow-up period. Only the most recent CRP and hemoglobin levels predicted the efficacy of infliximab treatment at approximately 14 weeks, a time point when the clinician often determines whether to continue treatment. Conclusion: Measurement of blood biomarkers prior to the clinical assessment does not predict the effectiveness of infliximab.

Heritability of tear fluid cytokines in healthy twins.

PURPOSE: Ocular surface disease is common and it is associated with elevated concentration levels of cytokines in tear fluid. Studies of the normal variation in tear fluid inflammatory markers are lacking. New knowledge may help guide research into ocular surface disease biomarkers and therapeutics. METHODS: In this prospective twin cohort study, healthy individuals were recruited from a population-based registry. Tear fluid was collected with the Schirmer test strips was submerged in phosphate buffered saline and stored at -80° before undergoing 27-cytokine multiplex immunoassay analysis. Broad-sense heritability (h2) of cytokine concentrations was analyzed. RESULTS: 90 participants (23 monozygotic and 22 dizygotic twin pairs) were included. Data availability allowed for heritability analysis of 15 cytokines, and a h2 >50% was seen for 10 cytokines. A statistical power of >80% was achieved for heritability analyses of the cytokines interferon gamma induced protein 10 (h2 = 94.8%), eotaxin (89.8%), interleukin 7 (86.6%), interleukin 1ß (82.2%) and monocyte chemoattractant protein 1 (68.2%). CONCLUSIONS: The tear fluid concentration of several analyzed cytokines was found to be highly heritable. A considerable amount of the inter-individual variation observed for the concentration of certain tear fluid cytokines can be linked to hereditary factors that cannot easily be modified by changing factors in the environment of patients. This suggests that a higher success in ocular surface disease drug discovery may be anticipated for drugs that have targets in specific populations, and points to the importance of emphasizing known preventive measures of ocular surface disease and examinations of close relatives of patients with ocular surface disease, such as dry eye disease.

Protocol for the combined cardiometabolic deep phenotyping and registry-based 20-year follow-up study of the Inter99 cohort.

INTRODUCTION: The population-based Inter99 cohort has contributed extensively to our understanding of effects of a systematic screening and lifestyle intervention, as well as the multifactorial aetiology of type 2 diabetes (T2D) and cardiovascular disease. To understand causes, trajectories and patterns of early and overt cardiometabolic disease manifestations, we will perform a combined clinical deep phenotyping and registry follow-up study of the now 50-80 years old Inter99 participants. METHODS AND ANALYSIS: The Inter99 cohort comprises individuals aged 30-60 years, who lived in a representative geographical area of greater Copenhagen, Denmark, in 1999. Age-stratified and sex-stratified random subgroups were invited to participate in either a lifestyle intervention (N=13 016) or questionnaires (N=5264), while the rest served as a reference population (N=43 021). Of the 13 016 individuals assigned to the lifestyle intervention group, 6784 (52%) accepted participation in a baseline health examination in 1999, including screening for cardiovascular risk factors and prediabetic conditions. In total, 6004 eligible participants, who participated in the baseline examination, will be invited to participate in the deep phenotyping 20-year follow-up clinical examination including measurements of anthropometry, blood pressure, arterial stiffness, cardiometabolic biomarkers, coronary artery calcification, heart rate variability, heart rhythm, liver stiffness, fundus characteristics, muscle strength and mass, as well as health and lifestyle questionnaires. In a subsample, 10-day monitoring of diet, physical activity and continuous glucose measurements will be performed. Fasting blood, urine and faecal samples to be stored in a biobank. The established database will form the basis of multiple analyses. A main purpose is to investigate whether low birth weight independent of genetics, lifestyle and glucose tolerance predicts later common T2D cardiometabolic comorbidities. ETHICS AND DISSEMINATION: The study was approved by the Medical Ethics Committee, Capital Region, Denmark (H-20076231) and by the Danish Data Protection Agency through the Capital Region of Denmark's registration system (P-2020-1074). Informed consent will be obtained before examinations. Findings will be disseminated in peer-reviewed journals, at conferences and via presentations to stakeholders, including patients and public health policymakers. TRIAL REGISTRATION NUMBER: NCT05166447.

Frail inner limiting membrane maculopathy suggested to describe a new retinal Alport-like condition with two variants in three generations of females.

BACKGROUND: We report a three-generation family with isolated Alport-like retinal abnormalities in the absence of lenticonus, hearing loss, kidney disease, and detectable molecular genetic defects in known Alport-related genes. METHODS: Clinical examination includes ocular biomicroscopy, fundus photography, optical coherence tomography, dipstick urinalysis, serum creatinine assessment, and molecular genetic analysis. RESULTS: The proband, her mother, and her maternal grandmother had normal best-corrected visual acuity and normal visual fields in both eyes. The macula presented a petaloid stair-case profile with scarce vessels in both eyes of the proband and a flat temporal macula lacking a foveal avascular zone in her mother and her grandmother. No family member had renal symptoms, unexplained subnormal hearing, or lenticonus. Sequencing and MLPA found no defect in COL4A3, COL4A4, and COL4A5. Common SNPs around the genes ± 1Mb showed no segregation. Furthermore, none of the variants shared between the affected individuals in genes from a gene panel of genes relevant for ophthalmopathy nor whole exome- and genome sequencing explained the phenotype. CONCLUSION: A new condition with two retinal Alport-like phenotypes was found. No abnormalities of the kidneys and lens were found, neither abnormalities of the type IV collagen genes related to Alport syndrome. Homology with retinal abnormalities seen in patients after surgical removal of the inner limiting membrane of the retina suggests that this is where the defect is located. We therefore suggest that the new retinal phenotypes and similar phenotypes can be described with the new definition "frail inner limiting membrane maculopathy."

Paternal preconception exposure to non-steroid anti-inflammatory drugs or opioids and adverse birth outcomes: A nationwide registry-based cohort study.

BACKGROUND AND AIM: Paternal use of analgesics during the time of conception and adverse birth outcomes are poorly studied. We investigated the association between paternal exposure to non-steroid anti-inflammatory drugs and opioids within 3 months before the date of conception and the risk of adverse birth outcomes (preterm birth, small for gestational age, low Apgar score, and major congenital malformations). METHODS: We used nationwide data from the Danish health registers. We included information on all singleton live births, and their fathers and mothers from 1997 to 2018. We created two exposed cohorts, children with preconception paternal exposure to (1) non-steroid anti-inflammatory drugs and (2) opioids. The unexposed cohort was children without preconception paternal exposure to non-steroid anti-inflammatory drugs or opioids, and we performed a sub-analysis against paternal use of acetaminophen (paracetamol). We used logistic regression models to estimate the odds ratios of adverse birth outcomes including 95% confidence intervals. RESULTS: We identified 1,260,934 children, 45,667 children with paternal exposure to non-steroid anti-inflammatory drugs, 10,086 children with paternal exposure to opioids, and 1,205,181 unexposed children. The adjusted odds ratio for preterm birth was 1.08 (95% confidence interval, 1.03-1.13) after paternal exposure to non-steroid anti-inflammatory drugs and 1.21 (95% confidence interval, 1.08-1.35) after paternal exposure to opioids. The adjusted odds ratio for small for gestational age was 1.09 (95% confidence interval, 1.03-1.17) after paternal exposure to non-steroid anti-inflammatory drugs, and 1.03 (95% confidence interval, 0.88-1.21) after paternal exposure to opioids. We found null-associations for a low Apgar score and major congenital malformations. Estimates were attenuated when compared against paternal paracetamol exposure. CONCLUSIONS: Overall, we found null-associations across the comparisons made. Weak associations were found for paternal exposure to non-steroid anti-inflammatory drugs or opioids and preterm birth and small for gestational age, but not with low Apgar score or major congenital malformation. All associations were attenuated when compared against an active comparator of paternal paracetamol exposure. The effect sizes were small and less likely to be of clinical relevance.

Retraction of cystoid macular edema from the fovea after intravitreal anti-VEGF therapy for birdshot chorioretinopathy.

PURPOSE: To report the effect of anti-vascular endothelial growth factor inhibitor (anti-VEGF) on fovea-involving cystoid macular edema in a patient with Birdshot chorioretinopathy. METHODS: A 42-year-old male patient presented to our hospital with bilateral posterior uveitis with retinal vasculitis, cystoid macular edema and optic disc edem a. He was diagnosed with birdshot chorioretinopathy based on clinical appearance and tissue type HLA-A29. RESULTS: The patient underwent vitrectomy in the right eye without any change in visual acuity. Retinal leakage was reduced by oral prednisolone, which could not be tapered below 50 mg per day without relapse. Oral prednisolone, topical dexamethasone and subtenonal kenalog were associated with intraocular pressure rise in both eyes. Hence, his uveitis responded to steroids, but there was no detectable effect of any steroid-sparing immunomodulatory drugs. The patient had been on oral prednisolone 50 mg for five years when it was decided to attempt intravitreal VEGF inhibitor injection therapy. The anti-VEGF therapy diminished cystoid macular edema in the fovea and improved the visual acuity. CONCLUSION: Here we report for the first time the long-term outcomes of anti-VEGF injections on fovea-involving cystoid macular edema in Birdshot chorioretinopathy to keep steroid at the minimal possible doses and preserve a satisfying visual acuity level.

Inflammatory Bowel Disease in Adults and Elderly: The Use of Selected Non-IBD Medication Examined in a Nationwide Cohort Study.

BACKGROUND: Real-world data on medications used for conditions other than inflammatory bowel disease (IBD) are sparse. We examined how the onset of IBD affects the prescription pattern of selected non-IBD medication and the risk of becoming an incident user. METHODS: This nationwide cohort study utilized data from Danish health registers. We included incident patients with young adult-onset IBD (18-39 years of age), adult-onset IBD (40-59 years of age), and elderly-onset IBD (60+ years of age), from 1998 to 2018 and followed all for 3 years. We examined redeemed prescriptions before and after the onset of IBD and estimated the risk of becoming a user of non-IBD medications using logistic regression models. RESULTS: We identified 36165 patients, 16 771 (46%) with young adult onset, 10615 (29%) with adult onset, and 8779 (24%) with elderly onset. The onset of IBD increased the use of antidepressants, antipsychotics, sedatives/hypnotics, opioids, nonopioid analgesics, antidiabetics, and proton pump inhibitors, even in patients with no other underlying comorbid diseases. The adjusted odds ratio for using antidepressants 1 year after the onset of IBD in elderly was 1.50 (95% confidence interval [CI], 1.14-1.82), in opioids 1.69 (95% CI, 1.45-1.95), in nonopioid analgesics 2.10 (95% CI, 1.77-2.48), in cardiovascular medication 2.20 (95% CI, 1.86-2.61), and in proton pump inhibitors 1.51 (95% CI, 1.31-1.74) compared with adults. CONCLUSIONS: In all 3 age groups, the proportions of patients with redeemed prescriptions for several groups of non-IBD medication were significantly increased after the IBD diagnosis compared with before. The risk of becoming an incident user for several groups of non-IBD medication was increased in elderly patients.

In patients with young adult onset, adult onset, and elderly onset of inflammatory bowel disease (IBD), the proportions of prescriptions for non-IBD medication was significantly increased after the IBD onset compared with before. The risk of new use of non-IBD medication was increased in elderly-onset IBD patients.

Tissue amount and diagnostic yield of a novel franseen EUS-FNB and a standard EUS-FNA needle-A randomized controlled study in solid pancreatic lesions.

Background and Objectives: Several types of needles are available for EUS-guided tissue sampling of pancreatic lesions. Whereas fine-needle aspiration (FNA) needles typically provide cytological samples, fine-needle biopsy (FNB) needles are designed to obtain microcores with preserved tissue architecture. The aim of this study was to compare tissue amount and diagnostic yield between a modified Franseen-type FNB needle (TopGain; Medi-Globe GmbH, Grassau, Germany) and a standard FNA needle. Methods: We performed a prospective, multicenter randomized controlled study between June 2020 and September 2021, including patients with a solid pancreatic lesion referred for EUS-guided tissue sampling at 3 centers in Denmark. The patients were randomized 1:1 to either FNA needle or the novel FNB needle. Primary outcomes included the number of obtained tissue microcores and total and diagnostic tissue area. Results: Sixty-four patients were included. The median number of tissue microcores procured per pass was significantly higher in the FNB group compared with FNA (3 vs. 2, P < 0.001). Similarly, the mean total tissue area (2.74 vs. 0.44 mm2, P < 0.001) and mean diagnostic tissue area (1.74 vs. 0.28 mm2, P < 0.001) were more than 6-fold larger in the FNB samples compared with FNA. The median number of passes needed for a diagnostic sample was 1 for the FNB needle and 2 for FNA needle (P = 0.12). The novel FNB needle provided a higher percentage of samples of excellent quality (P = 0.002). Conclusions: The novel Franseen-type FNB needle seems to be significantly superior to a conventional FNA needle. The results of this study underline excellent performance of crown-cut needles.

Ocular and systemic associations and heritability of retinal arterial wall-to-lumen ratios in a twin cohort.

PURPOSE: To investigate ocular and systemic factors associated with the retinal arterial wall-to-lumen ratio (WLR) and to determine the relative contribution of genetic and environmental variation to WLR in healthy adults. METHODS: This cross-sectional twin study included 78 monozygotic and 67 dizygotic same-sex twin pairs aged 58.4 ± 9.8 (mean ± SD) years. Lumen diameter (LD) and outer diameter (OD) of a superotemporal retinal artery were measured using adaptive optics fundus photography, and the WLR was calculated. Linear mixed model regression analysis of associations with WLR comprised the descriptive variables ocular axial length (AL), intraocular pressure (IOP), height, weight, body mass index (BMI), smoking, blood pressure, high density (HDL), low density (LDL) and very low density (VLDL) lipoproteins, total cholesterol and triglycerides. The relative influence of genes and environment on WLR was calculated through polygenetic modelling. RESULTS: Increasing age and arterial blood pressure were associated with a higher WLR, while increasing retinal artery OD and ocular AL were associated with a lower WLR. Sex, smoking status, BMI, IOP, cholesterol levels or triglycerides had no detectable impact on the WLR. Broad-sense heritability of WLR was 21% (95% CI: 1-41%), while environmental factors accounted for the remaining 79% of the interindividual variance (95% CI: 59-99%). CONCLUSION: Retinal artery wall thickness was closely linked to increasing age and higher arterial blood pressure, the latter being mediated by the environment over genes.

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.

Objective and subjective measures of sleep initiation are differentially associated with DNA methylation in adolescents.

INTRODUCTION: The onset of puberty is associated with a shift in the circadian timing of sleep, leading to delayed sleep initiation [i.e., later sleep onset time (SOT)] due to later bedtimes and/or longer sleep onset latency (SOL). Several genome-wide association studies (GWAS) have identified genes that may be involved in the etiology of sleep phenotypes. However, circadian rhythms are also epigenetically regulated; therefore, epigenetic biomarkers may provide insight into the physiology of the pubertal sleep onset shift and the pathophysiology of prolonged or delayed sleep initiation. RESULTS: The gene-wide analysis indicated differential methylation within or around 1818 unique genes across the sleep initiation measurements using self-report, actigraphy (ACT), and polysomnography (PSG), while GWAS-informed analysis yielded 67 genes. Gene hits were identified for bedtime (PSG), SOL (subjective, ACT and PSG) and SOT (subjective and PSG). DNA methylation within 12 genes was associated with both subjective and PSG-measured SOL, 31 with both ACT- and PSG-measured SOL, 19 with both subjective and ACT-measured SOL, and one gene (SMG1P2) had methylation sites associated with subjective, ACT- and PSG-measured SOL. CONCLUSIONS: Objective and subjective sleep initiation in adolescents is associated with altered DNA methylation in genes previously identified in adult GWAS of sleep and circadian phenotypes. Additionally, our data provide evidence for a potential epigenetic link between habitual (subjective and ACT) SOL and in-lab SOT and DNA methylation in and around genes involved in circadian regulation (i.e., RASD1, RAI1), cardiometabolic disorders (i.e., FADS1, WNK1, SLC5A6), and neuropsychiatric disorders (i.e., PRR7, SDK1, FAM172A). If validated, these sites may provide valuable targets for early detection and prevention of disorders involving prolonged or delayed SOT, such as insomnia, delayed sleep phase, and their comorbidity.

Visual Function and Inner Retinal Structure in Relation to Birth Factors in Autosomal Dominant Optic Atrophy.

Purpose: The extreme variation in expressivity of autosomal dominant optic atrophy (ADOA) is unexplained. It is present from early childhood, why there is reason to search for pre- and perinatal risk factors for poor vision in ADOA. The process of ganglion cell pruning in the fetus is of interest because mitochondria are involved in apoptosis. We hypothesized that suboptimal mitochondrial function makes the developing retina and optic nerve vulnerable to fetal stress in ADOA. We have examined visual function and inner retinal layer structure in relation to birth parameters in ADOA. Methods: The study included 142 participants with OPA1 ADOA, 62 unaffected first-degree relatives, and 90 unrelated control subjects. Outcome measures included best-corrected visual acuity, microperimetric sensitivity, nerve fiber layer (NFL) volume, and ganglion cell layer (GCL) volume. Descriptive parameters included birth weight, maternal age at birth, birth complications, and gestational age. Analysis was made using mixed modeling. Results: The analysis showed a significant positive association between microperimetric sensitivity and longer gestational age in ADOA (0.5 dB/week, P = 0.017). Interaction analysis showed a significant different association between microperimetric sensitivity and gestational age between participants with ADOA and the control groups (P = 0.007) and a significant difference in association between NFL volume and birth weight (P = 0.04) and gestational age (P = 0.02) between variant types. Conclusions: The study suggests that gestational age and birth weight may affect the expressivity of ADOA. The results support that prospectively collected pre- and perinatal data should be included in future studies of the natural history of ADOA.

Postpolymerization Modification by Nucleophilic Addition to Styrenic Carbodiimides.

Carbodiimides are electrophilic functional groups that react with select nucleophiles under mild conditions. However, their potential as platforms for postpolymerization modification has been relatively underexplored. We describe the synthesis and radical polymerization of a styrenic carbodiimide which undergoes rapid nucleophilic addition with primary and secondary alkyl amines under ambient conditions, even in the presence of other protic nucleophiles. The monomer is amenable to both free and controlled radical (co)polymerization, and we further demonstrate the utility of this approach by preparing covalent adaptable networks through guanylation of the styrenic carbodiimide with difunctional amines. These materials exhibit a variation in relaxation times according to both the guanidine structure and concentration, providing a facile means for tuning dynamic behavior.

Numerical Modeling of the Mixing of Highly Viscous Polymer Suspensions in Partially Filled Sigma Blade Mixers.

This paper presents a non-isothermal, non-Newtonian Computational Fluid Dynamics (CFD) model for the mixing of a highly viscous polymer suspension in a partially filled sigma blade mixer. The model accounts for viscous heating and the free surface of the suspension. The rheological model is found by calibration with experimental temperature measurements. Subsequently, the model is exploited to study the effect of applying heat both before and during mixing on the suspension's mixing quality. Two mixing indexes are used to evaluate the mixing condition, namely, the Ica Manas-Zlaczower dispersive index and Kramer's distributive index. Some fluctuations are observed in the predictions of the dispersive mixing index, which could be associated with the free surface of the suspension, thus indicating that this index might not be ideal for partially filled mixers. The Kramer index results are stable and indicate that the particles in the suspension can be well distributed. Interestingly, the results highlight that the speed at which the suspension becomes well distributed is almost independent of applying heat both before and during the process.

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.

Multicenter retrospective cohort of EUS-guided anterograde pancreatic duct access.

Background and study aims Pancreatic duct (PD) cannulation may be difficult during conventional endoscopic retrograde cholangiopancreatography (ERCP) due to underlying pathology, anatomical variants or surgically altered anatomy. Pancreatic access in these cases previously necessitated percutaneous or surgical approaches. Endoscopic ultrasound (EUS) allows for an alternative and can be combined with ERCP for rendezvous during the same procedure, or for other salvage options. Patients and methods Patients with attempted EUS access of the PD from tertiary referral centers between 2009 and 2022 were included in the cohort. Demographic data, technical data, procedural outcomes and adverse events were collected. The primary outcome was rendezvous success. Secondary outcomes included rates of successful PD decompression and change in procedural success over time. Results The PD was accessed in 105 of 111 procedures (95 %), with successful subsequent ERCP in 45 of 95 attempts (47 %). Salvage direct PD stenting was performed in 5 of 14 attempts (36 %). Sixteen patients were scheduled for direct PD stenting (without rendezvous) with 100 % success rate. Thus 66 patients (59 %) had successful decompression. Success rates improved from 41 % in the first third of cases to 76 % in the final third. There were 13 complications (12 %), including post-procedure pancreatitis in seven patients (6 %). Conclusions EUS-guided anterograde pancreas access is a feasible salvage method if retrograde access fails. The duct can be cannulated, and drainage can be achieved in the majority of cases. Success rates improve over time. Future research may involve investigation into technical, patient and procedural factors contributing to rendezvous success.