Technical Considerations in Laparoscopic-Assisted Endoscopic Retrograde Cholangiography.

The use of endoscopic retrograde cholangiography (ERCP) for diagnostic and therapeutic interventions on the pancreaticobiliary system has steadily increased, but the standard approach through the oropharynx is prohibited after Roux-en-Y (RYGB) gastric bypass surgery. Laparoscopic access to the gastric remnant allows for the completion of ERCP using the standard side-viewing duodenoscope to facilitate the completion of standard and advanced endoscopic maneuvers. Here, we describe our experience with the technical aspects of safe and effective performance of laparoscopic-assisted ERCP.

Clinical Impacts of Omalizumab on the Psychiatric Comorbidities of Chronic Spontaneous Urticaria: A Systematic Review and Meta-Analysis.

Individuals with chronic spontaneous urticaria (CSU) experience significant sleep disturbances and are at risk of anxiety and depression.

Three Year Outcomes of the Paul Glaucoma Implant for Treatment of Glaucoma.

PRECIS: In our case series, the three-year failure for PGI implantation was 14.6%. At three years post-operatively, there was a significant reduction in mean intraocular pressure and number of glaucoma medications used. PURPOSE: To determine 3-year efficacy and safety of the PAUL Glaucoma Implant (PGI), a novel glaucoma tube shunt in patients with glaucoma. METHODS: Retrospective review of all patients who had undergone PGI implantation in a single tertiary institution in Singapore between May 1, 2017, and Jan 1, 2022. Data was extracted from electronic health records (Computerized Patient Support System 2 and Epic). Primary outcome measure was failure, defined as IOP ≥18 mmHg or ≤6 mmHg on 2 consecutive visits after 3 months, reoperation for IOP-related indication, explantation of implant or loss of light perception vision. Complete success was defined as the absence of failure without medications at 36 months, and qualified success similarly, but with medications. Post-operative mean IOP, mean number of IOP-lowering medications used and visual acuity were also assessed. RESULTS: Forty-eight eyes in 48 patients were identified. Thirty-one patients (64.6%) had primary open angle and angle closure glaucoma, and 18 (37.5%) had previous existing tube implants or trabeculectomy. At 3 years post-operatively, 7 cases (14.6%) fulfilled criteria for failure and 36 (75%) met criteria for complete success. Mean IOP at 36 months was 14.9±4.11 mmHg, from mean pre-operative IOP of 20.6±6.13 mmHg ( P <0.001). Mean number of IOP-lowering medications used was reduced from 3.13±0.959 pre-operatively to 0.167±0.476 at 36 months ( P <0.001). The most common post-operative complication was hypotony (n=17, 35.4%), of which majority were self-limiting, followed by hyphema (n=5, 10.4%) and tube exposure (n=4, 8.3%). CONCLUSION: The PGI demonstrated sustained IOP reduction and a reduction of medication burden at 3 years post-operatively.

Oncogenic GNAS drives a gastric pylorus program in intraductal papillary mucinous neoplasms of the pancreas.

OBJECTIVE: Intraductal Papillary Mucinous Neoplasms (IPMNs) are cystic lesions and bona fide precursors for pancreatic ductal adenocarcinoma (PDAC). Recently, we showed that acinar to ductal metaplasia, an injury repair program, is characterized by a transcriptomic program similar to gastric spasmolytic polypeptide expressing metaplasia (SPEM), suggesting common mechanisms of reprogramming between the stomach and pancreas. The aims of this study were to assay IPMN for pyloric markers and to identify molecular drivers of this program. DESIGN: We analyzed RNA-seq studies of IPMN for pyloric markers, which were validated by immunostaining in patient samples. Cell lines expressing Kras G12D +/- GNAS R201C were manipulated to identify distinct and overlapping transcriptomic programs driven by each oncogene. A PyScenic-based regulon analysis was performed to identify molecular drivers in the pancreas. Expression of candidate drivers was evaluated by RNA-seq and immunostaining. RESULTS: Pyloric markers were identified in human IPMN. GNAS R201C drove expression of these markers in cell lines and siRNA targeting of GNAS R201C or Kras G12D demonstrates that GNAS R201C amplifies a mucinous, pyloric phenotype. Regulon analysis identified a role for transcription factors SPDEF, CREB3L1, and CREB3L4, which are expressed in patient samples. siRNA-targeting of Spdef inhibited mucin production. CONCLUSION: De novo expression of a SPEM phenotype has been identified in pancreatitis and a pyloric phenotype in Kras G12D -driven PanIN and Kras G12D ;GNAS R201C -driven IPMN, suggesting common mechanisms of reprogramming between these lesions and the stomach. A transition from a SPEM to pyloric phenotype may reflect disease progression and/or oncogenic mutation. IPMN-specific GNAS R201C amplifies a mucinous phenotype, in part, through SPDEF.

Treatment of Pyoderma Gangrenosum.

Pyoderma gangrenosum is a rare neutrophilic dermatosis that results in painful cutaneous ulcers and is frequently associated with underlying hematologic disorders, inflammatory bowel disease, or other autoimmune disorders. Pathogenesis involves an imbalance between proinflammatory and anti-inflammatory mediators, leading to tissue damage from neutrophils. First-line treatment options with the greatest evidence include systemic corticosteroids, cyclosporine, and tumor necrosis factor alpha inhibitors. Other steroid-sparing therapies such as dapsone, mycophenolate mofetil, intravenous immunoglobulin, and targeted biologic or small molecule inhibitors also have evidence supporting their use. Wound care and management of underlying associated disorders are critical parts of the treatment regimen.

Oncogenic Fatty Acid Metabolism Rewires Energy Supply Chain in Gastric Carcinogenesis.

BACKGROUND & AIMS: Gastric carcinogenesis develops within a sequential carcinogenic cascade from precancerous metaplasia to dysplasia and adenocarcinoma, and oncogenic gene activation can drive the process. Metabolic reprogramming is considered a key mechanism for cancer cell growth and proliferation. However, how metabolic changes contribute to the progression of metaplasia to dysplasia remains unclear. We have examined metabolic dynamics during gastric carcinogenesis using a novel mouse model that induces Kras activation in zymogen-secreting chief cells. METHODS: We generated a Gif-rtTA;TetO-Cre;KrasG12D (GCK) mouse model that continuously induces active Kras expression in chief cells after doxycycline treatment. Histologic examination and imaging mass spectrometry were performed in the GCK mouse stomachs at 2 to 14 weeks after doxycycline treatment. Mouse and human gastric organoids were used for metabolic enzyme inhibitor treatment. The GCK mice were treated with a stearoyl- coenzyme A desaturase (SCD) inhibitor to inhibit the fatty acid desaturation. Tissue microarrays were used to assess the SCD expression in human gastrointestinal cancers. RESULTS: The GCK mice developed metaplasia and high-grade dysplasia within 4 months. Metabolic reprogramming from glycolysis to fatty acid metabolism occurred during metaplasia progression to dysplasia. Altered fatty acid desaturation through SCD produces a novel eicosenoic acid, which fuels dysplastic cell hyperproliferation and survival. The SCD inhibitor killed both mouse and human dysplastic organoids and selectively targeted dysplastic cells in vivo. SCD was up-regulated during carcinogenesis in human gastrointestinal cancers. CONCLUSIONS: Active Kras expression only in gastric chief cells drives the full spectrum of gastric carcinogenesis. Also, oncogenic metabolic rewiring is an essential adaptation for high-energy demand in dysplastic cells.

Differential spatial distribution of HNF4α isoforms during dysplastic progression of intraductal papillary mucinous neoplasms of the pancreas.

Hepatocyte Nuclear Factor 4-alpha (HNF4α) comprises a nuclear receptor superfamily of ligand-dependent transcription factors that yields twelve isoforms in humans, classified into promoters P1 or P2-associated groups with specific functions. Alterations in HNF4α isoforms have been associated with tumorigenesis. However, the distribution of its isoforms during progression from dysplasia to malignancy has not been studied, nor has it yet been studied in intraductal papillary mucinous neoplasms, where both malignant and pre-malignant forms are routinely clinically identified. We examined the expression patterns of pan-promoter, P1-specific, and P2-specific isoform groups in normal pancreatic components and IPMNs. Pan-promoter, P1 and P2 nuclear expression were weakly positive in normal pancreatic components. Nuclear expression for all isoform groups was increased in low-grade IPMN, high-grade IPMN, and well-differentiated invasive adenocarcinoma. Poorly differentiated invasive components in IPMNs showed loss of all forms of HNF4α. Pan-promoter, and P1-specific HNF4α expression showed shifts in subnuclear and sub-anatomical distribution in IPMN, whereas P2 expression was consistently nuclear. Tumor cells with high-grade dysplasia at the basal interface with the stroma showed reduced expression of P1, while P2 was equally expressed in both components. Additional functional studies are warranted to further explore the mechanisms underlying the spatial and differential distribution of HNF4α isoforms in IPMNs.

Comparable outcomes of reverse shoulder arthroplasty for proximal humerus fractures and for rotator cuff arthropathy in a predominantly asian population.

Background: Reverse shoulder arthroplasty (RSA) was initially developed for rotator cuff arthropathy but has been expanded to treat comminuted proximal humerus fractures. Few studies have compared RSA for traumatic and degenerative indications. We present the first report of mid-term outcomes of RSA comparing both indications in an Asian population. Methods: 113 degenerative and 20 fracture patients underwent RSA from 2010 to 2019. Patients with degenerative indications were 4:1 propensity-score matched to fractures and adjusted for age and sex. Patients were assessed for range of motion (ROM), strength, pain, Constant-Murley score (CMS), University of California Los Angeles Shoulder Score (UCLA) and Oxford shoulder score (OSS) preoperatively, at 6-months and 1-year. Patients' satisfaction, expectation fulfilment and minimal clinically important difference (MCID) were analysed. Results: Degenerative patients had better ROM, isometric strength and CMS at 6-months, although at 1-year only abduction was superior (104.8 ± 17.3° vs 86.7 ± 19.8°). No significant differences in pain, UCLA and OSS were observed. Most improvements occurred within 6 months. Similar proportions of patients were satisfied (83.3% vs 73.3%, p = 0.460) and attained MCID (85.0% vs 86.7%, p = 1.000) at 1-year. Discussion: Although initially exhibiting slower recovery, patients with proximal humerus fractures can expect similar functional recovery and satisfaction at 1-year compared to those who received RSA for degenerative indications.

Popular large language model chatbots' accuracy, comprehensiveness, and self-awareness in answering ocular symptom queries.

In light of growing interest in using emerging large language models (LLMs) for self-diagnosis, we systematically assessed the performance of ChatGPT-3.5, ChatGPT-4.0, and Google Bard in delivering proficient responses to 37 common inquiries regarding ocular symptoms. Responses were masked, randomly shuffled, and then graded by three consultant-level ophthalmologists for accuracy (poor, borderline, good) and comprehensiveness. Additionally, we evaluated the self-awareness capabilities (ability to self-check and self-correct) of the LLM-Chatbots. 89.2% of ChatGPT-4.0 responses were 'good'-rated, outperforming ChatGPT-3.5 (59.5%) and Google Bard (40.5%) significantly (all p < 0.001). All three LLM-Chatbots showed optimal mean comprehensiveness scores as well (ranging from 4.6 to 4.7 out of 5). However, they exhibited subpar to moderate self-awareness capabilities. Our study underscores the potential of ChatGPT-4.0 in delivering accurate and comprehensive responses to ocular symptom inquiries. Future rigorous validation of their performance is crucial to ensure their reliability and appropriateness for actual clinical use.

The double-lasso loop technique of Biceps tenodesis has lower displacement after cyclic loading, compared to interference screw fixation: Biomechanical analysis in an ovine model.

Background: Biceps tenodesis is an effective treatment for symptomatic long head of biceps tendon pathology. Recently the arthroscopic "double lasso-loop" suture anchor (DLSA) technique was described, advantaged by reduced cost, complexity, and operative time. We aimed to compare the in vitro strength of DLSA with conventional interference screws (IS). Methods: A biomechanical analysis was conducted on 14 sheep shoulders (8 DLSA, 6 IS), consisting of a 500-cycle cyclic loading experiment of 5-70 N and ultimate failure load (UFL) test where each specimen was pulled until failure. Displacement (mm) was recorded every 100 cycles, while stiffness and UFL were observed. Results: Cyclic displacement was significantly lower with DLSA at 100 cycles, but not above. During the UFL test, IS was stiffer (27.68 ± 6.56 N/mm versus 14.10 ± 5.80 N/mm, p = .005) and had higher UFL (453.67 ± 148.55 N versus 234.22 ± 44.57 N, p = .001) than DLSA. All DLSA failures occurred with suture/anchor pull-out, while all IS constructs failed at the muscle/tendon. Discussion: Comparison of the novel DLSA technique with a traditional IS method found lower initial displacement. While our IS constructs could withstand higher UFL, peak load characteristics of DLSA were similar to previous ovine studies. Hence, the DLSA technique is a viable alternative to IS for biceps tenodesis with its purported non-biomechanical advantages.

Investigating the determinants of iridolenticular contact area: a novel parameter for angle closure.

BACKGROUND/AIMS: To identify ocular determinants of iridolenticular contact area (ILCA), a recently introduced swept-source optical coherence tomography (SSOCT) derived parameter, and assess the association between ILCA and angle closure. METHODS: In this population-based cross-sectional study, right eyes of 464 subjects underwent SSOCT (SS-1000, CASIA, Tomey Corporation, Nagoya, Japan) imaging in the dark. Eight out of 128 cross-sectional images (evenly spaced 22.5° apart) were selected for analysis. Matlab (Matworks, Massachusetts, USA) was used to measure ILCA, defined as the circumferential extent of contact area between the pigmented iris epithelium and anterior lens surface. Gonioscopic angle closure (GAC) was defined as non-visibility of the posterior trabecular meshwork in two or more angle quadrants. RESULTS: The mean age of subjects was 62±6.6 years, with the majority being female (65.5%). 143/464 subjects (28.6%) had GAC. In multivariable linear regression analysis, ILCA was significantly associated with anterior chamber width (ß=1.03, p=0.003), pupillary diameter (ß=-1.9, p<0.001) and iris curvature (ß=-17.35, p<0.001). ILCA was smaller in eyes with GAC compared with those with open angles (4.28±1.6 mm2 vs 6.02±2.71 mm2, p<0.001). ILCA was independently associated with GAC (ß=-0.03, p<0.001), iridotrabecular contact index (ß=-6.82, p<0.001) or angle opening distance (ß=0.02, p<0.001) after adjusting for covariates. The diagnostic performance of ILCA for detecting GAC was acceptable (AUC=0.69). CONCLUSIONS: ILCA is a significant predictor of angle closure independent of other biometric factors and may reflect unique anatomical information associated with pupillary block. ILCA represents a novel biometric risk factor in eyes with angle closure.

Benchmarking large language models' performances for myopia care: a comparative analysis of ChatGPT-3.5, ChatGPT-4.0, and Google Bard.

BACKGROUND: Large language models (LLMs) are garnering wide interest due to their human-like and contextually relevant responses. However, LLMs' accuracy across specific medical domains has yet been thoroughly evaluated. Myopia is a frequent topic which patients and parents commonly seek information online. Our study evaluated the performance of three LLMs namely ChatGPT-3.5, ChatGPT-4.0, and Google Bard, in delivering accurate responses to common myopia-related queries. METHODS: We curated thirty-one commonly asked myopia care-related questions, which were categorised into six domains-pathogenesis, risk factors, clinical presentation, diagnosis, treatment and prevention, and prognosis. Each question was posed to the LLMs, and their responses were independently graded by three consultant-level paediatric ophthalmologists on a three-point accuracy scale (poor, borderline, good). A majority consensus approach was used to determine the final rating for each response. 'Good' rated responses were further evaluated for comprehensiveness on a five-point scale. Conversely, 'poor' rated responses were further prompted for self-correction and then re-evaluated for accuracy. FINDINGS: ChatGPT-4.0 demonstrated superior accuracy, with 80.6% of responses rated as 'good', compared to 61.3% in ChatGPT-3.5 and 54.8% in Google Bard (Pearson's chi-squared test, all p ≤ 0.009). All three LLM-Chatbots showed high mean comprehensiveness scores (Google Bard: 4.35; ChatGPT-4.0: 4.23; ChatGPT-3.5: 4.11, out of a maximum score of 5). All LLM-Chatbots also demonstrated substantial self-correction capabilities: 66.7% (2 in 3) of ChatGPT-4.0's, 40% (2 in 5) of ChatGPT-3.5's, and 60% (3 in 5) of Google Bard's responses improved after self-correction. The LLM-Chatbots performed consistently across domains, except for 'treatment and prevention'. However, ChatGPT-4.0 still performed superiorly in this domain, receiving 70% 'good' ratings, compared to 40% in ChatGPT-3.5 and 45% in Google Bard (Pearson's chi-squared test, all p ≤ 0.001). INTERPRETATION: Our findings underscore the potential of LLMs, particularly ChatGPT-4.0, for delivering accurate and comprehensive responses to myopia-related queries. Continuous strategies and evaluations to improve LLMs' accuracy remain crucial. FUNDING: Dr Yih-Chung Tham was supported by the National Medical Research Council of Singapore (NMRC/MOH/HCSAINV21nov-0001).

Understanding Treatment Preferences Among People Living with HIV in Australia: A Discrete Choice Experiment.

Purpose: To better understand what is most important to people living with human immunodeficiency virus (PLWH) when choosing their treatment. We assessed how PLWH trade off the potential risks and benefits of oral and long acting injectable (LAI) treatments. Participants and Methods: Firstly, in-depth interviews were conducted with 11 PLWH to develop a holistic understanding of experiences and determine attributes that contribute to treatment decision-making. Secondly, a discrete choice experiment (DCE) was used to understand the treatment preferences for PLWH with n = 99 PLWH aged 18 years or over with a diagnosis of human immunodeficiency virus (HIV) and who were currently using anti-retroviral therapy (ART). Study participants were presented with 12 scenarios and asked to select their preferred treatment among two hypothetical injectable treatment alternatives, "injection 1" and "injection 2" and their current oral ART treatment. The DCE data were modelled using a latent class model (LCM). Results: The model revealed significant heterogeneity in preferences for treatment attributes among study participants. Two segments/classes of PLWH were identified. The first segment expressed a strong preference for their current oral treatment; the second segment showed strong preference for the injection treatment and for it to be administered in a GP clinic. Overall, out-of-pocket cost was the most important attribute for participants. One-third of PLWH were willing to switch to an LAI. Conclusion: Not all PLWH valued the same treatment attributes equally. Overall, out-of-pocket costs for treatments were considered by respondents as the most determining factor in making treatment choices. Results have important implications for healthcare policy and will serve to better inform patients and stakeholders involved in the treatment decision-making process about the treatment preferences of PLWH. Clinicians are encouraged to consider shared decision-making to establish the treatment course that best aligns with PLWH's treatment goals.