Heterogenous thinning of peripapillary tissues occurs early during high myopia development in juvenile tree shrews.

Myopia is an independent risk factor for glaucoma, but the link between both conditions remains unknown. Both conditions induce connective tissue remodeling at the optic nerve head (ONH), including the peripapillary tissues. The purpose of this study was to investigate the thickness changes of the peripapillary tissues during experimental high myopia development in juvenile tree shrews. Six juvenile tree shrews experienced binocular normal vision, while nine received monocular -10D lens treatment starting at 24 days of visual experience (DVE) to induce high myopia in one eye and the other eye served as control. Daily refractive and biometric measurements and weekly optical coherence tomography scans of the ONH were obtained for five weeks. Peripapillary sclera (Scl), choroid-retinal pigment epithelium complex (Ch-RPE), retinal nerve fiber layer (RNFL), and remaining retinal layers (RRL) were auto-segmented using a deep learning algorithm after nonlinear distortion correction. Peripapillary thickness values were quantified from 3D reconstructed segmentations. All lens-treated eyes developed high myopia (-9.8 ± 1.5 D), significantly different (P < 0.001) from normal (0.69 ± 0.45 D) and control eyes (0.76 ± 1.44 D). Myopic eyes showed significant thinning of all peripapillary tissues compared to both, normal and control eyes (P < 0.001). At the experimental end point, the relative thinning from baseline was heterogeneous across tissues and significantly more pronounced in the Scl (-8.95 ± 3.1%) and Ch-RPE (-16.8 ± 5.8%) when compared to the RNFL (-5.5 ± 1.6%) and RRL (-6.7 ± 1.8%). Furthermore, while axial length increased significantly throughout the five weeks of lens wear, significant peripapillary tissue thinning occurred only during the first week of the experiment (until a refraction of -2.5 ± 1.9 D was reached) and ceased thereafter. A sectorial analysis revealed no clear pattern. In conclusion, our data show that in juvenile tree shrews, experimental high myopia induces significant and heterogeneous thinning of the peripapillary tissues, where the retina seems to be protected from profound thickness changes as seen in Ch-RPE and Scl. Peripapillary tissue thinning occurs early during high myopia development despite continued progression of axial elongation. The observed heterogeneous thinning may contribute to the increased risk for pathological optic nerve head remodeling and glaucoma later in life.

Predictors and Etiologies of Clinical Relapse Among Patients With Ulcerative Colitis in Deep Remission.

GOAL: The objective of this study was to evaluate for potential predictors and etiologies of clinical relapse among patients with ulcerative colitis in deep remission. BACKGROUND: Patients displaying deep (endoscopic and histologic) remission have a decreased cumulative risk of relapse in ulcerative colitis of <10% per year, but predictors and etiologies of relapse in this population are poorly understood. MATERIALS AND METHODS: We performed a retrospective cohort study utilizing electronic medical records at Tufts Medical Center to identify patients in deep remission, classified as having both endoscopic remission (Mayo Endoscopic Score of 0 or 1) and histologic remission (Simplified Geboes Score 0.2). We evaluated the cumulative risk of clinical relapse following attainment of deep remission and examined predictors and etiologies of relapse. RESULTS: Among 139 patients with ulcerative colitis in deep remission, the cumulative risk of relapse was <10% and <20% at 1 and 2 years. Patients with complete normalization of mucosa (Geboes=0) and normalization of C-reactive protein (<7.48 mg/dL) at the time of remission were associated with a lower risk of relapse. Discontinuation of therapy was the most commonly identified etiology of relapse. CONCLUSIONS: Patients in deep remission have a 1-year risk of clinical relapse of <10%, with those demonstrating a non-normalized mucosa or elevated C-reactive protein predictive of persistent relapse risk. Discontinuation of therapy or minor histologic changes may drive relapse among those in deep remission.

Efficacy and Safety of Hyperbaric Oxygen Therapy in Fistulizing Crohn's Disease: A Systematic Review and Meta-analysis.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) delivers 100% oxygen in a pressurized chamber, increasing tissue oxygen levels and regulating inflammatory pathways. Mounting evidence suggests that HBOT may be effective for inflammatory bowel disease. Our systematic review and meta-analysis aimed to quantify the efficacy and safety of HBOT in fistulizing Crohn's disease (CD). METHODS: A systematic review was conducted using the EMBASE, Web of Science, Pubmed, and Cochrane Library databases according to the "Preferred Reporting Items for Systematic Reviews and Meta-analyses" criteria. Study bias was assessed using the Cochrane Handbook guidelines. RESULTS: Sixteen studies with 164 patients were included in the analysis. For all fistula subtypes, the pooled overall clinical response was 87% (95% CI: 0.70-0.95, I2 = 0) and the pooled clinical remission was 59% (95% CI: 0.35-0.80, I2 = 0). The overall clinical response was 89%, 84%, and 29% for perianal, enterocutaneous, and rectovaginal fistulas, respectively. On meta-regression, hours in the chamber and the number of HBOT sessions were not found to correlate with clinical response. The pooled number of adverse events was low at 51.7 per 10,000 HBOT sessions for all fistula types (95% CI: 16.8-159.3, I2 = 0). The risk of bias was observed across all studies. CONCLUSION: HBOT is a safe and potentially effective treatment option for fistulizing CD. Randomized control trials are needed to substantiate the benefit of HBOT in fistulizing CD.

Prognostic Value of Inflammatory Bowel Disease-associated Biomarkers in Patients With Immune Checkpoint Inhibitor Enterocolitis: A Retrospective Cohort Study.

In the emerging field of immune checkpoint inhibitor enterocolitis, biomarkers to predict disease course are lacking. Select genetic polymorphisms (ATG16L1T300A) and serum amyloid A warrant further study as potential biomarkers associated with severe ICI enterocolitis.

Longitudinal Changes of Bruch's Membrane Opening, Anterior Scleral Canal Opening, and Border Tissue in Experimental Juvenile High Myopia.

Purpose: To investigate the relative positional changes between the Bruch's membrane opening (BMO) and the anterior scleral canal opening (ASCO), and border tissue configuration changes during experimental high myopia development in juvenile tree shrews. Methods: Juvenile tree shrews were assigned randomly to two groups: binocular normal vision (n = 9) and monocular -10 D lens treatment starting at 24 days of visual experience to induce high myopia in one eye while the other eye served as control (n = 12). Refractive and biometric measurements were obtained daily, and 48 radial optical coherence tomography B-scans through the center of the optic nerve head were obtained weekly for 6 weeks. ASCO and BMO were segmented manually after nonlinear distortion correction. Results: Lens-treated eyes developed high degree of axial myopia (-9.76 ± 1.19 D), significantly different (P < 0.001) from normal (0.34 ± 0.97 D) and control eyes (0.39 ± 0.88 D). ASCO-BMO centroid offset gradually increased and became significantly larger in the experimental high myopia group compared with normal and control eyes (P < 0.0001) with an inferonasal directional preference. The border tissue showed a significantly higher tendency of change from internally to externally oblique configuration in the experimental high myopic eyes in four sectors: nasal, inferonasal, inferior, and inferotemporal (P < 0.005). Conclusions: During experimental high myopia development, progressive relative deformations of ASCO and BMO occur simultaneously with changes in border tissue configuration from internally to externally oblique in sectors that are close to the posterior pole (nasal in tree shrews). These asymmetric changes may contribute to pathologic optic nerve head remodeling and an increased risk of glaucoma later in life.

Predictive Model for Positive Video Capsule Endoscopy in Iron Deficiency Anemia.

BACKGROUND AND AIMS: Bleeding from the gastrointestinal tract can contribute to the development of iron deficiency anemia (IDA) among individuals without another obvious source of bleeding. In order to identify patients most likely to benefit from examination of the small bowel, our aim was to create a risk score for positive video capsule endoscopy (VCE) in IDA utilizing a multicenter collection of studies. METHODS: We performed a retrospective multicenter study utilizing VCE studies performed for an indication of IDA between 1/1/2005 and 7/31/2018. VCE findings were graded based on the P0-P2 grading system. The primary outcome of interest was a positive (P2) VCE. Data were analyzed with Student's t test for continuous variables and the Fisher's exact test for categorical variables. Logistic regression was used to identify independent associations with positive VCE. RESULTS: In total, 765 VCE procedures were included with 355 (46.5%) male subjects and a median age of 63.2 (SD 15.3) years. One hundred ninety studies (24.8%) were positive (P2) for small bowel bleeding. Four variables associated with positive VCE which were incorporated into a point scoring system: (+) 1 for age ≥ 66 years, active smoking and cardiac arrythmia and (-) 1 for preceding hemoglobin level ≥ 8.5. The risk probabilities for positive VCE-assigned scores - 1, 0, 1, and 2 + were 12.3% (95% CI 7.3-17.3%), 20% (14.9-25.1%), 34.8% (28.6-41%), and 39% (30-47.8%). CONCLUSION: In order to improve the diagnostic yield of capsule examinations, risk factors should be applied to clinical decision-making. We created a risk score for positive VCE in IDA, including the risk factors of age, smoking, history of cardiac arrythmia, and preceding hemoglobin level.

Case report: human granulocytic anaplasmosis causes acute myopericarditis with atrial fibrillation.

Background: Tick-borne illness are becoming increasingly common, in a spreading geographic area. Lyme disease is a well-known cause of cardiovascular disease, but anaplasmosis has previously had relatively little reported association with conduction and myocardial disease. Case Summary: A 65-year-old man with fever and malaise was admitted to the intensive care unit in shock. Electrocardiogram showed new atrial fibrillation and conduction abnormalities. Transthoracic echocardiogram demonstrated normal left ventricular ejection fraction but significant right ventricle dysfunction. Cardiac magnetic resonance imaging findings were consistent with myopericarditis. Workup revealed human granulocytic anaplasmosis without Lyme. He recovered with doxycycline. Conclusion: To our knowledge, this is one of the first reported cases of anaplasmosis causing electrical conduction and myocardial disease with haemodynamic instability in an isolated infection. Treatment with appropriate antibiotics and supportive care allowed the patient to recover to his functional baseline within a month from being discharged from the hospital. Recognition of anaplasmosis in the absence of Lyme disease as a potential cause of electrical and myocardial disease is important in the context of increasing anaplasmosis incidence across the United States.

Diagnosis and Classification of Inflammatory Bowel Disease Strictures.

Intestinal strictures are a common complication in inflammatory bowel disease (IBD). Symptoms due to intestinal strictures range from mild bloating and/or abdominal discomfort to complete bowel obstruction. Careful selection of available medical, endoscopic, or surgical therapies is critical for optimizing patient outcomes and is dependent on the effective characterization of the stricture. This article will focus on the diagnosis and classification of IBD strictures.

Recommendations on the Appropriate Management of Steroids and Discharge Planning During and After Hospital Admission for Moderate-Severe Ulcerative Colitis: Results of a RAND Appropriateness Panel.

INTRODUCTION: Limited guidance exists for the postdischarge care of patients with ulcerative colitis hospitalized for moderate-severe flares. METHODS: RAND methodology was used to establish appropriateness of inpatient and postdischarge steroid dosing, discharge criteria, follow-up, and postdischarge biologic or small molecule initiation. A literature review informed on the panel's voting, which occurred anonymously during 2 rounds before and after a moderated virtual session. RESULTS: Methylprednisolone 40-60 mg intravenous every 24 hours or hydrocortisone 100 mg intravenous 3 times daily is appropriate for inpatient management, with methylprednisolone 40 mg being appropriate if intolerant of higher doses. It is appropriate to discharge patients once rectal bleeding has resolved (Mayo subscore 0-1) and/or stool frequency has returned to baseline frequency and form (Mayo subscore 0-1). It is appropriate to discharge patients on 40 mg of prednisone after observing patients for 24 hours in hospital to ensure stability before discharge. For patients being discharged on steroids without in-hospital biologic or small molecule therapy initiation, it is appropriate to start antitumor necrosis factor (TNF) therapy after discharge for anti-TNF-naive patients. For anti-TNF-exposed patients, it is appropriate to start vedolizumab or ustekinumab for all patients and tofacitinib for those with a low risk of adverse events. It is appropriate to follow up patients clinically within 2 weeks and with lower endoscopy within 4-6 months after discharge. DISCUSSION: We provide recommendations on the inpatient and postdischarge management of patients with ulcerative colitis hospitalized for moderate-severe flares.

Natural History of New-onset Inflammatory Bowel Disease Among Patients With Multiple Sclerosis.

Patients with MS and IBD were as likely to have stricturing, fistulizing, and extensive IBD as IBD controls. Although MS-IBD patients were less likely to initiate anti-TNF therapy, they did not have worsened risk of progression to surgery on follow-up.

Scleral crosslinking using genipin can compromise retinal structure and function in tree shrews.

Scleral crosslinking using genipin has been identified as a promising treatment approach for myopia control. The efficacy of genipin to alter biomechanical properties of the sclera has been shown in several animal models of myopia but its safety profile remains unclear. In this safety study, we aim to investigate the effect of scleral crosslinking using retrobulbar injections of genipin on retinal structure and function at genipin doses that were shown to be effective in slowing myopia progression in juvenile tree shrews. To this end, three or five retrobulbar injections of genipin at 0 mM (sham), 10 mM, or 20 mM were performed in one eye every other day. Form deprivation myopia was induced in the injected eye. We evaluated retinal function using full-field electroretinography and retinal structure using in vivo optical coherence tomography imaging and ex vivo histology. The optical coherence tomography results revealed significant thinning of the peripapillary retinal nerve fiber layer in all genipin treated groups including the lowest dose group, which showed no significant treatment effect in slowing myopia progression. In contrast, inducing form deprivation myopia alone and in combination with sham injections caused no obvious thinning of the retinal nerve fiber layer. Electroretinography results showed a significant desensitizing shift of the b-wave semi-saturation constant in the sham group and the second highest genipin dose group, and a significant reduction in b-wave maxima in the two highest genipin dose groups. The ex vivo histology revealed noticeable degeneration of photoreceptors and retinal pigment epithelium in one of two investigated eyes of the highest genipin dose group. While scleral crosslinking using genipin may still be a feasible treatment option for myopia control, our results suggest that repeated retrobulbar injections of genipin at 10 mM or higher are not safe in tree shrews. An adequate and sustained delivery strategy of genipin at lower concentrations will be needed to achieve a safe and effective scleral crosslinking treatment for myopia control in tree shrews. Caution should be taken if the proposed treatment approach is translated to humans.

Effect of different preconditioning protocols on the viscoelastic inflation response of the posterior sclera.

Preconditioning by repeated cyclic loads is routinely used in ex vivo mechanical testing of soft biological tissues. The goal of preconditioning is to achieve a steady and repeatable mechanical response and to measure material properties that are representative of the in vivo condition. Preconditioning protocols vary across studies, and their effect on the viscoelastic response of tested soft tissue is typically not reported or analyzed. We propose a methodology to systematically analyze the preconditioning process with application to inflation testing. We investigated the effect of preconditioning on the viscoelastic inflation response of tree shrew posterior sclera using two preconditioning protocols: (i) continuous cyclic loading-unloading without rest and (ii) cyclic loading-unloading with 15-min rest between cycles. Posterior scleral surface strain was measured using three-dimensional Digital Image Correlation (3D-DIC). We used five variables of characterizing features of the stress-strain loop curve to compare the two preconditioning protocols. Our results showed protocol-dependent differences in the tissue response during preconditioning and at the preconditioned state. Incorporating a resting time between preconditioning cycles significantly decreased the number of cycles (10.5 ± 2.9 cycles vs. 3.1 ± 0.5 cycles, p < 0.001) but increased the total time (15.8 ± 4.4 min vs. 51.2 ± 8.3 min, p < 0.001) needed to reach preconditioned state. At the preconditioned state, 2 of 5 characteristic variables differed significantly between protocols: hysteresis loop area (difference=0.023 kJ/m3, p = 0.0020) and elastic modulus at high IOPs (difference=24.0 MPa, p = 0.0238). Our results suggest that the analysis of the preconditioning process is an essential part of inflation experiments and a prerequisite to properly characterize the tissue viscoelastic response. Furthermore, material properties obtained at the preconditioned state can be impacted by the resting time used during preconditioning and may not be directly compared across studies if the resting time varies by 15 min between studies. STATEMENT OF SIGNIFICANCE: Although applying a preconditioning protocol by repeated cyclic loads is common practice in ex vivo mechanical characterization of soft tissues, the tissue response is typically not reported or analyzed, and the protocol's potential effect on the response remains unclear. This is partially caused by lack of a standardized methodology to precondition soft tissues. We present the first systematic analysis of two representative preconditioning protocols used during inflation testing in ocular biomechanics. Our results show protocol-dependent differences in the viscoelastic response during the preconditioning process and at the preconditioned state. Consequently, the analysis of the preconditioning response represents an essential part of mechanical testing and a prerequisite to properly characterize the tissue viscoelastic response. The effect of preconditioning on the preconditioned state response must be considered when comparing results across studies with different preconditioning protocols.

Effect of Scleral Crosslinking Using Multiple Doses of Genipin on Experimental Progressive Myopia in Tree Shrews.

Purpose: To evaluate the effect of scleral crosslinking (SXL) on slowing experimental progressive myopia in tree shrew eyes using sub-Tenon's injections of genipin (GEN) at different concentrations and number of injections. Methods: Three or five sub-Tenon's injections of GEN at 0 mM (sham), 10 mM, or 20 mM were performed in one eye every other day starting at 18 days of visual experience. Form deprivation (FD) myopia was induced in the injected eye between 24 and 35 days of visual experience; the fellow eye served as control. Tree shrews were randomly assigned to five experimental groups: FD (n = 8); FD + 5 × sham injections (n = 6); FD + 3 × GEN injections at 10 mM (n = 6) and 20 mM (n = 6); and FD + 5 × GEN injections at 20 mM (n = 6). Refractive state and ocular dimensions were measured daily. Results: Compared with the FD group, the sham-injected group showed a transient effect on slowing vitreous chamber elongation. With increasing GEN dose, SXL had an increasing treatment effect on slowing vitreous chamber elongation and myopia progression. In addition, SXL led to a dose-dependent shortening of the aqueous chamber depth and corneal thickening. Lens thickening was observed in the group with the highest concentration. Conclusions: We have shown that SXL using GEN can slow axial elongation and myopia progression in tree shrews. The extent of this treatment effect was dose dependent. Several unexpected effects were observed (corneal thickening, decrease of the anterior chamber depth, and lens thickening), which require further optimization of the GEN delivery approach before clinical consideration. Translational Relevance: The results of this preclinical study suggest that scleral crosslinking using genipin can slow myopia progression.

Endoscopic evaluation of surgically altered bowel in inflammatory bowel disease: a consensus guideline from the Global Interventional Inflammatory Bowel Disease Group.

The majority of patients with Crohn's disease and a proportion of patients with ulcerative colitis will ultimately require surgical treatment despite advances in diagnosis, therapy, and endoscopic interventions. The surgical procedures that are most commonly done include bowel resection with anastomosis, strictureplasty, faecal diversion, and ileal pouch. These surgical treatment modalities result in substantial alterations in bowel anatomy. In patients with inflammatory bowel disease, endoscopy plays a key role in the assessment of disease activity, disease recurrence, treatment response, dysplasia surveillance, and delivery of endoscopic therapy. Endoscopic evaluation and management of surgically altered bowel can be challenging. This consensus guideline delineates anatomical landmarks and endoscopic assessment of these landmarks in diseased and surgically altered bowel.

P014 Postoperative Recurrence in Crohn's Disease Patients Treated with Adalimumab versus Infliximab: A Systematic Review and Meta-Analysis.

BACKGROUND: Up to 80% of patients with Crohn's disease (CD) undergo intestinal resection at one point. However, the risk of post-operative recurrence (POR) increases with time, with half of these patients developing recurrence at five years after surgery. Treatment with anti-tumor necrosis factor (anti-TNF) agents has been shown to decrease the risk of clinical and endoscopic recurrence post-operatively. This meta-analysis aims to compare the rate of the two mostly commonly used anti-TNF agents (infliximab (IFX) and adalimumab (ADA)) and their efficacy in maintaining clinical and endoscopic remission in CD patients who were treated with adalimumab versus infliximab after surgery. METHODS: A comprehensive search of Medline, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Scopus was conducted from each database's inception to May 29th 2021. Comparative studies assessing the efficacy and safety of infliximab and adalimumab for postoperative CD patients were included. Primary outcomes included postoperative clinical and endoscopic remission. Secondary outcome was the risk of adverse events due to anti-TNF agents. Pooled event rates were calculated per person-year of follow-up. RESULTS: Four studies with total of 361 CD patients were included in the final analysis. Our meta-analysis showed no statistically significant difference in maintaining clinical and endoscopic remission rates between patients treated with infliximab and those with adalimumab (Pooled incidence rate ratio of 0.75 (95% CI 0.43-1.3), and 0.94 (95% CI 0.71-1.2), respectively) (Figure 1A, 2A). There were low to moderate heterogeneities (I2 = 57.1% for clinical remission and I2 = 0% for endoscopic remission). The funnel plot in each analysis indicated no publication bias, which was supported by Begg's and Egger's tests (Figure 1B, 2B). There was also no significant difference in the risk of adverse events between the two groups (RR= 0.56, 95% CI 0.068-4.5) (Figure 3). CONCLUSION: Our meta-analysis demonstrated comparable efficacy of infliximab and adalimumab in maintaining post-operative clinical and endoscopic remission in Crohn's disease, with similar rates of adverse events. Our meta-analysis was limited by the small number of total studies and patients included and the lack of randomized controlled trials.

Emerging use of artificial intelligence in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a complex, immune-mediated gastrointestinal disorder with ill-defined etiology, multifaceted diagnostic criteria, and unpredictable treatment response. Innovations in IBD diagnostics, including developments in genomic sequencing and molecular analytics, have generated tremendous interest in leveraging these large data platforms into clinically meaningful tools. Artificial intelligence, through machine learning facilitates the interpretation of large arrays of data, and may provide insight to improving IBD outcomes. While potential applications of machine learning models are vast, further research is needed to generate standardized models that can be adapted to target IBD populations.

Management of Incidental Pancreatic Cystic Lesions: Integrating Novel Diagnostic and Prognostic Factors With Current Clinical Guidelines.

Owing to increased detection rates, the diagnosis and management of incidental pancreatic cysts has become a common predicament. Up to 13% of patients undergoing cross-sectional imaging studies for other indications are found to have pancreatic cystic lesions. Although most cystic lesions are benign, the malignant potential of several types of pancreatic cysts makes accurate classification vital to directing therapy. To this end, advances in the last decade led to better characterization of pancreatic cyst morphology and hence enhanced the ability to predict underlying histopathology, and biological behavior. Although accurate classification remains a challenge, the utilization of complementary diagnostic tools is the optimal approach to dictate management. The following review includes a description of pancreatic cysts, a critical review of current and emerging diagnostic techniques and a review of recent guidelines in the management of incidental pancreatic cysts.