Introduction

The mainstay first-line treatment of acute severe ulcerative colitis (ASUC) is high dose steroids. One-third of ASUC patients are steroid refractory and will require rescue therapy, either with cyclosporine (CYC) or infliximab (IFX) to reduce the risk of colectomy. It is recommended that patients are assessed on day 3 of steroid therapy to stratify risk of colectomy and therefore guide need of rescue therapy. It is generally understood that prolonged exposure to high dose steroids carries risk of infection, poor wound healing and mood disturbances. However, the optimum duration of intravenous steroids that mitigates risk and improves patient outcomes has not been well-established. Similarly, early rescue therapy in steroid refractory ASUC is also recommended. Delayed rescue therapy initiation may predict a longer hospital length of stay (LOS), but there is limited literature that assesses the effect of delayed rescue therapy on other patient outcomes.

Aims & Methods

All ASUC presentations to a Quaternary Sydney hospital over a 10-year period were included. A modified True-love Witts’ Criteria was used to identify ASUC as ≥6 bloody bowel motions daily and presence of at least one systemic feature, including heart rate >90 bpm, temperature >37.8°C, haemoglobin <105 g/L, and C-reactive protein (CRP) ≥30 mg/L. IV hydrocortisone was given at a dose of 100 mg four times daily. Short course IV steroids was defined as ≤5 days and prolonged course of IV steroids was defined as >5 days. Rescue therapy used were either Cyclosporine (CYC), Infliximab (IFX) or JAK inhibitors (Upadacitinib or Tofacitinib). Early and delayed rescue therapy was defined as rescue therapy given within ≤5 days and at >5 days, respectively.

Results

A total of 172 presentations met criteria for ASUC. Of these presentations, 69.7% (n=120) received ≤5 days of IV steroid therapy, whilst 30.2% (n=52) received >5 days. A total of 34.9% (n=60) of patients required rescue therapy. Of those requiring rescue therapy, CYC was used in 26.3% (n=15), IFX was used in 73.7% (n=42) and JAK inhibitors in 5% (n=3). The mean time to rescue therapy was 5.67 days. Rescue therapy was given in ≤5 days for 53.3% (n=32) and >5 days in 46.7% (n=28) of presentations. The mean days on IV steroids in those who required rescue therapy was 6.95 days compared to 4.03 days in those who did not (p<0.01). Table 1 compares outcomes in those who received short and prolonged courses of IV steroids. Table 2 compares outcomes in those who received early and delayed rescue therapy.

Table 1. Comparison of outcomes in patients who received short and prolonged courses of IV steroids, and early and delayed rescue therapy

Conclusion

Patients who received shorter courses of IV steroids and early rescue therapy were less likely to receive total parenteral nutrition (TPN) but no impact was seen on other clinical outcomes. Patients requiring rescue therapy were on IV steroids for a longer period of time compared to those who did not. However, giving early rescue therapy significantly reduces the amount of time on IV steroids and overall length of stay. Further research is required to assess whether this may significantly reduce the risk of steroid side-effects and hospital-associated infections.

Introduction

Recent studies have revealed that liquid-liquid phase separation (LLPS) plays a critical role in tumorigenesis. Myotilin (MYOT), a key component of actin cross-linking protein complexes, is involved in regulating myofibril assembly and maintaining the structural integrity of Z-discs in muscle cells. Intriguingly, MYOT contains intrinsically disordered regions (IDRs) and has been implicated in the migration of gastric cancer. However, whether MYOT undergoes LLPS and whether this process contributes to gastric cancer progression remains unexplored.

Aims & Methods

We aimed to investigate whether MYOT undergoes LLPS and its potential role in gastric cancer progression.
Differential gene expression analysis was performed on gastric cancer samples from our sequencing data and validated using public databases. The Disprot, Database of Protein Disorder was used to predict the IDRs of MYOT. Fluorescence recovery after photobleaching (FRAP) and cellular immunofluorescence were explored to assess MYOT’s ability to undergo LLPS. Cell proliferation, apoptosis and migration assay were conducted to investigate the potential role of MYOT in gastric cancer. Actin polymerization assays were performed to evaluate the qualitative effects of purified MYOT on actin polymerization.

Results

Differential gene expression analysis revealed that MYOT was significantly downregulated in gastric cancer tissues compared to adjacent normal tissues, a finding further confirmed by RT-qPCR. In the prediction of protein structure, it can be found that MYOT contains extensive IDRs. FRAP analysis demonstrated rapid fluorescence recovery in GFP-MYOT droplets within minutes, suggesting dynamic LLPS behavior. Similarly, purified GFP-MYOT exhibited fusion behaviors, further supporting its capacity for LLPS in vitro. Overexpression of MYOT did not significantly affect gastric cancer cell proliferation or apoptosis, but reduced cell migration. Actin polymerization failed to occur both in the GFP-MYOT and GFP control samples.

Conclusion

Our findings demonstrate that MYOT suppresses gastric cancer cell migration and purified GFP-MYOT does not directly promote on actin polymerization, implicating its potential role as a tumor suppressor. Additionally, MYOT undergoes LLPS both in vitro and in vivo, as evidenced by FRAP. We propose that MYOT may exert its anti-tumor effects through LLPS-mediated mechanisms, offering a novel perspective on its function in gastric cancer progression.

Introduction

Contemporary studies suggest there are racial disparities in the outcomes of acute presentations. This study aimed to investigate the impact of sex and race on the management and outcomes of patients presenting with upper gastrointestinal bleeding (UGIB).

Aims & Methods

Using International Classification of Diseases 10th Revision Codes, all adults >18 admitted from 2016–2020 with a discharge diagnosis of UGIB were extracted from the National Inpatient Sample.

Results

In over 900,000 hospitalisations for UGIB, 69.4%, 14.1%, 9.6%, 3.6%, 0.9% and 2.4% were for admissions in white, black, Hispanic, Asian/pacific islander, native American and ‘other’ patients respectively. Comorbidity burden varied between racial groups (p<0.001). White patients had higher crude rates of endoscopy, and comparable rates of surgery or interventional radiology to control blood loss, in comparison to other racial groups. Adjusted analysis revealed that black and Asian/pacific islander racial group patients had lower odds of in-hospital all cause mortality compared to white patients, but ‘other’ racial group patients had higher odds of mortality (p<0.001). There was no difference for Hispanic or native American patients. For non-variceal bleeding, these outcomes persisted. However, for variceal bleeds, there were no significant differences in outcomes between each racial group.

Conclusion

There are racial disparities in the management and outcomes of admissions for UGIB. These difference persist despite the aetiology of bleeding. Underlying reasons for differences in outcomes must be investigated to ensure improved outcomes across high-risk patient groups.

Introduction

Upper gastrointestinal bleeding (UGIB) is a major cause of mortality in the United States (US). This study aimed to investigate the contemporary trends in the management and outcomes of these patients as well as factors associated with in-hospital mortality, using national data.

Aims & Methods

The US National Inpatient Sample was queried from 2016-2020. Using International Classification of Diseases 10th Revision Codes, all adults >18 admitted with a principal discharge diagnosis of UGIB were extracted along with data about demographics, management and outcomes. Categorical variables were compared using chi-squared and expressed as percentages (%). Logistic regression was performed, adjusting for variables associated with adverse outcomes and reported as adjusted odds ratios (aOR) with 95% confidence intervals (CI). Data were considered significant if p<0.001.

Results

There were 918,925 hospitalizations for UGIB in the study period. Variceal bleeding occurred in 36,050 (3.9%) of admissions. Endoscopy was performed in 451,450 (49.1%) of admissions, with 10,160 (1.1%) of admissions and 9,355 (1.0%) of admissions requiring interventional radiology and gastrointestinal surgery to control blood loss respectively. The crude rate of all-cause in-hospital mortality was 1.9%. Factors associated with death included variceal bleed (aOR 2.84 CI 2.67-3.02), age (aOR 1.03 CI 1.03-1.03), history of cancer (aOR 2.45 CI 2.35-2.56), ulcer disease (aOR 1.44 CI 1.39-1.49), chronic renal failure (aOR 1.34 CI 1.29-1.37), chronic obstructive pulmonary disease (aOR 1.29 CI 1.24-1.34), receipt of endoscopy (aOR 1.33 CI 1.29-1.38), surgery (aOR 3.92 CI 3.63-4.24) and interventional radiology (aOR 3.33 CI 3.09-3.58).

Conclusion

UGIB remains a significant cause of hospitalisation in the US. Knowledge of the contemporary trends and outcomes of this patient group is important to improve management in this at-risk patient group.

Introduction

The prevalence of adenoma in patients with positive fecal immunochemical tests (FIT) is shown to be higher. Increased adenoma detection and removal during colonoscopy have been shown to prevent CRC and interval cancers. However, there is considerable variation in the adenoma detection rate (ADR) among colonoscopies performed for FIT. We hypothesize that the ability of dye-based chromoendoscopy to stain the colorectal lesion and their borders and increase their contrast against the normal colorectal mucosa would enhance the detection of adenoma and non-polypoid colorectal neoplasms (NPCRN) in patients undergoing FIT positive colonoscopy. In this randomized control trial, we aim to compare the effectiveness of pan-colonic indigo carmine chromoendoscopy (PCC) to high-definition white light colonoscopy (WLC) in individuals undergoing colonoscopy for positive FIT test.

Aims & Methods

Patients undergoing colonoscopy after a FIT positive test were randomized 1:1 to undergo PCC or WLC. The study was conducted between January 2021 to May 2023 at the Singapore General Hospital, Singapore. Colonoscopy was performed by general and advanced endoscopists, and all received training on PCC before the study. The primary outcome was ADR between the two groups. The secondary outcomes were advanced adenoma detection rate (AADR), NPCRN detection rate, sessile serrated lesion detection rate (SSLDR), and withdrawal time between the groups. We used the two-tailed Mann–Whitney U test and Chi-squared statistics for comparison. The ethics committee approved the study, and it was registered with clinicaltrials.gov (NCT04512612)

Results

We recruited 256 patients (PCC-128; WLC-128). The mean age of the entire cohort was 66 + 8.4 years. The mean ADR was comparable between PCC and WLC (70.3% vs. 64.8%, p-0.350). Likewise, the AADR (19.5% vs. 14.8%, p-0.320], and SSLDR (6.25% vs. 1.56%, p-0.102] were similar between the two groups. We found PCC detected more diminutive adenomas (0.97% vs. 0.58%, p-0.025] and NPCRN per colonoscopy (0.35% vs. 0.17%, p-0.028). The mean withdrawal time was longer with PCC compared to WLC (13.3 min vs. 10.2 min, p-0.001). General and advanced endoscopists had no difference in performance measures for APC and NPCRN per colonoscopy.

Conclusion

The ADR in FIT-positive colonoscopy is higher, and both PCC and WLC yielded comparable results. PCC merits consideration because of its increased ability to detect NPCRNs, which are precursors for interval cancer.

Introduction

Thyroidectomy is one of the most common surgical procedures worldwide, yet its potential effects on esophageal function remain inadequately characterized. While post-thyroidectomy issues such as voice changes have been well-documented, alterations in esophageal motility following this procedure have received limited attention in scientific literature.

Aims & Methods

This study aims to evaluate the impact of thyroidectomy on esophageal motility parameters using High-resolution manometry (HRM), with particular attention to upper esophageal sphincter (UES) function. Seventeen patients (11 females), who were to undergo total thyroidectomy or hemithyroidectomy, were prospectively recruited between the months of February and May 2023. Ten of them had goiters, while seven had thyroid nodules. Exclusion criteria were having an age under 30 or over 70 years old, having to also undergo a parathyroid surgery and taking medications that could alter the esophageal sphincter. All of them underwent a pre-operative HRM and a second one thirty days after surgery. HRM were performed according to the Chicago Classification 4.0 and the data were analyzed using the online analysis platform “Swallow Gateway”. Gastrointestinal (GI) symptoms were assessed using a standardized questionnaire, before the first and the second HRM. No after procedural complication was reported.

Results

UES function significatively changed after thyroidectomy, as it is shown by HRM metrics such as Pharyngeal Contractile Integral (CI), Velopharyngeal CI, Hypopharyngeal CI, UES-CI, UES Integrated Relaxation Pressure (UES-IRP), Post-Deglutitive UES CI, Proximal Contractile Integral (PCI), which all significatively decreased (p < 0.05) at the HRM performed after surgery. Compared to Swallow Gateway normal values, there was an important increase of pathological HRM metrics after thyroidectomy. No significant HRM difference was found between the two categories of patients (goiter and thyroid nodules) and no significant correlation was registered between GI symptoms pre- and post-surgery and between GI symptoms and HRM metrics.

Conclusion

Thyroidectomy may significantly affect esophageal motility, especially the function of the upper esophageal sphincter. This finding could be useful in the diagnostic and therapeutic pathway of these patients, although further and larger studies are required to confirm this result.

Introduction

Primary biliary cholangitis (PBC) is often associated with extrahepatic autoimmune diseases (EAIDs) such as Sjögren’s syndrome, autoimmune thyroiditis, and connective tissue disorders. While this association suggests a shared immunological predisposition, its effect on disease prognosis remains unclear.

Aims & Methods

This retrospective study included 69 patients diagnosed with PBC, excluding those with overlap syndromes involving autoimmune hepatitis. Patients were divided into two groups: isolated PBC (n = 35) and PBC associated with EAIDs (n = 34). The two groups were compared based on clinical, immunological, elastometric characteristics, disease progression, and prognostic scores (Paris I, Paris II, Rotterdam, Barcelona, Rochester, GLOBE, UK-PBC). Statistical analysis was conducted using appropriate tests, with a significance threshold set at p < 0.05.

Results

The average age at diagnosis was 55.6 years. The disease was initially suspected based on functional symptoms in 39% of cases (fatigue, pruritus, arthralgia), biological cholestasis in 33.3%, and decompensated cirrhosis in 20.3%. The most common associated autoimmune diseases were Sjögren’s syndrome (17.4%), thyroid disorders (13%), and systemic lupus erythematosus (10.1%). All patients received treatment with ursodeoxycholic acid at 13-15 mg/kg/day. No significant differences were found between the two groups regarding functional symptoms, biological markers (bilirubin, albumin, prothrombin time), autoantibodies (AMA, Anti-GP210, anti-SP100, anti-PML), non-invasive fibrosis scores (Fib4, Fibroindex, Fibroscan, S-index), or hepatic complications (HDH, cirrhosis, hepatic encephalopathy, liver-related death). Prognostic scores were also comparable between both groups: Paris I (p = 0.468), Paris II (p = 0.519), GLOBE score (p = 0.6), UK-PBC (p = 0.49), Rotterdam (p = 0.897), Barcelona (p = 0.181), Rochester (p = 0.727).

Conclusion

The presence of extrahepatic autoimmune diseases in PBC does not appear to affect the clinical, biological, or prognostic profiles of patients. Despite their frequency, these comorbidities do not seem to influence the progression of PBC.

Disclosure

None.