Introduction

Colonoscopy is a critical diagnostic and therapeutic procedure in gastroenterology. However, it carries risks, including hypoxemia, which can impact patient safety. Understanding the factors that contribute to the incidence of severe hypoxemia, specifically the role of procedure duration, is essential for improving patient outcomes.

Aims & Methods

This study aims to elucidate the relationship between the length of colonoscopy procedures and the occurrence of severe hypoxemia. We conducted a retrospective cohort study at Sheba Medical Center, Israel, including 21,524 adult patients who underwent colonoscopy from January 2020 to January 2024. The study focused on the incidence of severe hypoxemia, defined as a drop in oxygen saturation below 90%. Sedation protocols, involving a combination of Fentanyl, Midazolam, and Propofol, were personalized based on the endoscopist's discretion. Data were collected from electronic health records, covering patient demographics, clinical scores, sedation and procedure details, and outcomes. Statistical analyses, including logistic regression, were used to examine the association between procedure duration and hypoxemia, adjusting for various patient and procedural factors.

Results

The study found a significant correlation between colonoscopy duration and the risk of hypoxemia. Short procedures (under 20 minutes) had a 17.3% incidence of hypoxemia, which increased to 36.1% for procedures lasting over 60 minutes. Age and procedure duration were significant predictors of hypoxemia, with older patients and longer procedures associated with higher risks. The analysis highlighted the need for careful sedation management, especially in longer procedures.
Table 1- patient characteristics and outcomes based on the colonoscopy duration

Conclusion

The duration of colonoscopy procedures significantly impacts the risk of severe hypoxemia, with longer durations associated with higher risks. This study underscores the importance of optimizing procedural efficiency and tailoring sedation protocols to individual patient risk profiles to enhance the safety of colonoscopy. Further research is needed to develop strategies that minimize procedure duration without compromising the quality of care, thereby reducing the risk of hypoxemia and improving patient safety.

Introduction

Upadacitinib, a selective JAK inhibitor, is approved for moderate-to-severe Crohn’s disease (CD). However, real-world data on its effectiveness and safety, particularly in highly refractory populations, remain scarce. The UPITA-Crohn registry was established to evaluate the outcomes of upadacitinib in clinical practice across multiple centers in Andalusia, Spain.

Aims & Methods

This ambispective, multicenter registry included 142 patients with refractory CD treated with upadacitinib in 12 Andalusian hospitals. Clinical and biochemical data were collected at baseline, weeks 12 and 16, and at 6 months. Clinical remission (CR) was defined as a Harvey-Bradshaw Index (HBI) <5; clinical-biochemical remission (CBR) as HBI <5, CRP <5 mg/L, and fecal calprotectin <250 μg/g; and steroid-free remission (SFR) as HBI <5 without corticosteroids from week 12. Outcomes were also analyzed overall and according to prior exposure to advanced therapies.

Results

The UPITA-Crohn registry cohort included 142 patients with refractory Crohn’s disease. The mean age was 40.8 years (range 18–76), with 40% male. The mean disease duration at the time of upadacitinib initiation was 13.3 years (range 1–42), with a mean of 2.7 failed advanced therapies, highlighting a population with longstanding and complex disease. Most patients had ileocolonic involvement (50%), 22% had perianal disease, and 32% had previously undergone resective surgery.
The majority (74.4%) received induction with upadacitinib 45 mg for 12 weeks. At week 12, clinical remission was achieved by 54% of patients, with 15% reaching clinical-biochemical remission. At 6 months, among those still on treatment, 48.3% maintained clinical remission, 16.1% achieved clinical-biochemical remission, and 18.4% achieved steroid-free remission (Table 1).
When stratified by prior therapy, 6-month clinical remission was similar between patients with ≥2 prior advanced therapies (48.5%) and those with only 1 prior therapy (47.4%), with no significant difference. Steroid-free and clinical-biochemical remission rates were also slightly higher among less refractory patients, but differences were modest.
A total of 31 patients (21.8%) discontinued upadacitinib before 6 months, mainly due to primary non-response (70.9%). Adverse events were reported in 21.1% of patients, most commonly infections (9 cases), acne (7), transient transaminase elevation (5), and herpes zoster (2). Seven discontinuations were due to serious adverse events, including thrombosis, stroke, myocardial infarction, fever, and severe infections.

Table 1: Effectiveness Outcomes

Conclusion

Upadacitinib demonstrated meaningful effectiveness and a manageable safety profile in a real-world cohort of refractory Crohn’s disease patients. Notably, clinical remission rates remained stable even in those with multiple prior advanced therapies, suggesting upadacitinib may be a valuable option for patients with limited alternatives.

Introduction

Direct-acting antivirals (DAA) have revolutionized the treatment landscape for chronic hepatitis C (CHC), yielding notably high sustained virological response (SVR) rates. While SVR is associated with reduced hepatocellular carcinoma (HCC) risk, recent studies emphasize the importance of ongoing surveillance, particularly in patients with advanced fibrosis (F3-F4), mainly within the initial three years post-SVR.

Aims & Methods

The aim of this study was to assess the risk of hepatocellular carcinoma over a five-year period following DAA-induced SVR in a real-life cohort of F3-F4 patients.
Data were retrospectively collected from CHC F3-F4 patients initiating DAA treatment between February 2015 and January 2017 at a tertiary center. Statistical analysis was performed with SPSS 29.0 (significance level ≤0.05).

Results

Out of 239 patients included (69.5% male; median age: 58 years), a SVR at 12 weeks rate of 96.6% was achieved. Among those with SVR and continued follow-up (n=229), 5.2% (n=12) developed HCC over the five-year period, with 50% occurring more than three years post-SVR.
The annual HCC incidence rate was 1.1 cases/100 person-years (33.3% HCC-related mortality rate). Most HCC cases occurred in males (75%) and cirrhotic patients (75%, Child-Pugh A: 77.8%). The mean alpha-fetoprotein level at HCC diagnosis was 156.1 ng/mL. Additionally, 75% of patients who developed HCC had other co-factors for liver disease, mainly metabolic. Comparing the presence of other liver disease co-factors, no statistically significant difference was found between those who developed HCC and those who did not during the five-year follow-up period (p-value 0.267).

Conclusion

The incidence rate of HCC post- SVR has been reported to be 0.9-2.96/100 person-years for DAA therapy, consistent with the findings of this investigation. Nevertheless, our study underscores that the risk of HCC persists for at least five years following SVR, warranting long-term surveillance. Contrary to previous research, there is insufficient evidence to support the involvement of other co-factors in HCC development.

Disclosure

Hsu CC, Gopalakrishna H, Mironova M, Lee MH, Chen CJ, Yang HI, Wiese M, Chang KM, Wright EC, Abijo T, Feld JJ, Kaplan DE. Risk of Hepatocellular Carcinoma After Spontaneous Clearance of Hepatitis C Virus and in Noncirrhosis Chronic Hepatitis C Patients With Sustained Virological Response: A Systematic Review. Clin Infect Dis. 2023 Aug 14;77(Suppl 3):S245-S256. doi: 10.1093/cid/ciad380. PMID: 37579210; PMCID: PMC10425144.
Li M, Li Y, Zhang Y, Wang X, Lin C. Five-year follow-up of sustained virological response with hepatitis C infection after direct-acting antiviral therapy: A single-center retrospective study. Medicine (Baltimore). 2024 Feb 16;103(7):e37212. doi: 10.1097/MD.0000000000037212. PMID: 38363923; PMCID: PMC10869073.

Introduction

The recommended treatment for severe complications of portal hypertension (PH) is transjugular intrahepatic portosystemic shunt (TIPS) implantation. Despite alcohol-related liver disease (ALD) representing the most frequent cause of advanced chronic liver disease (ACLD) and PH, literature on the effects of ongoing alcohol use (AU) after TIPS placement currently remains scarce.

Aims & Methods

The study population consisted of patients with ALD-related ACLD who had undergone TIPS implantation at two Viennese tertiary care centers (pooled cohort from the prospective AUTIPS study, NCT03409263: 01/2017-11/2022; and a retrospective cohort: 09/2000-09/2019). Through the electronic patient management system, individual demographic, laboratory, and clinical data were retrieved. AU after TIPS placement was investigated according to clinical documentation, serum ethanol quantification if available, and patients' reporting.

Results

Overall, the study population consisted of 276 patients (median follow-up 29 [IQR 54] months), 196 (71.0%) of which had received TIPS for refractory ascites while in 80 (29.0%) the indication for TIPS implantation had been variceal hemorrhage. The median age was 56 (IQR 13) years and 215 (77.9%) of the patients were men. At the time of the TIPS insertion, the median MELD was 11 (IQR 9) and 38 (13.8%) individuals were classified as Child-Pugh C. AU after TIPS placement was documented in 85 (30.8%) study participants. Baseline characteristics at TIPS implantation were similar in patients with and without post-TIPS AU, specifically regarding the prevalence of ascites (p=0.51), variceal hemorrhage (p=0.87), and hepatic encephalopathy (p=0.87).
Bacterial infections were more frequently detected among patients with ongoing AU (log-rank p=0.002). Importantly, patients with ongoing AU showed a higher incidence of acute-on-chronic liver failure (ACLF; log-rank p<0.001) and higher overall mortality (log-rank p=0.005; including liver-related death [log-rank p<0.001]).
Furthermore, cumulative incidence of ACLF (p=0.014) and liver-related death (p=0.004) were significantly higher in patients with ongoing AU. Of note, ongoing AU was independently associated with ACLF (asHR: 1.66; 95%CI: 1.13-2.44; p=0.010) and liver-related death (asHR: 2.09; 95%CI: 1.32-3.33; p=0.002) in multivariable competing risks regression analysis adjusted for age, MELD, and portal pressure gradient after TIPS implantation.

Conclusion

AU represents an independent risk factor for outcome deterioration after TIPS placement. These findings emphasize the paramount role of psychiatric care and harm reduction measures in addition to hepatological optimization after TIPS implantation.

Disclosure

C.S. received travel support from Gilead, Abbvie, Galapagos and Gebro; speaking honoraria from Abbvie and Gilead; and payments for consulting from Gilead.
M.S. received travel support from MSD, Sandoz, BMS, Abbvie and Gilead; and speaking honoraria from BMS.
M.J. received speaking honoraria from Abbvie and Gilead.
T.R. received grant support from Abbvie, Boehringer- Ingelheim, Gilead, MSD, Philips Healthcare, Gore; speaking honoraria from Abbvie, Gilead, Gore, Intercept, Roche, MSD; consulting/advisory board fee from Abbvie, Bayer, Boehringer-Ingelheim, Gilead, Intercept, MSD, Siemens; and travel support from Boehringer-Ingelheim, Gilead, and Roche.
M.M. served as a speaker and/or consultant and/or advisory board member for AbbVie, Bristol-Myers Squibb, Collective Acumen, Gilead, and W. L. Gore & Associates and received travel support from AbbVie, Bristol-Myers Squibb, and Gilead.
B.S. received travel support from AbbVie and Gilead.

Introduction

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a disease that complements Nonalcoholic Fatty Liver Disease (NAFLD) and is newly defined in 2020. It is defined based on metabolic abnormalities, regardless of the presence of liver disease caused by other causes such as alcohol consumption. Regarding the newly defined MAFLD, there has not been many studies related to the prevalence and risk factors in Korea, and no studies were found targeting soldiers, especially pilots.

Aims & Methods

The purpose of this study is to identify prevalence and risk factors for MAFLD in Korean air force army inclusive of pilots. The subjects are 1044 soldiers who underwent health checkups in Korean Air Force Aerospace medical center from January 2020 to December 2022. The data was retrospectively collected including age, height, weight, body mass index, waist circumference, blood pressure, smoking, drinking, exercise intensity, various blood test results, presence of fatty liver, and degree of fatty liver. Risk factors were analyzed using logistic regression.

Results

There were 667 pilots (64%) in our study, of whom 477 (72%) were high-performing pilots. The prevalence of MAFLD was 316 (30%) in all soldier. There was difference in the prevalence of MAFLD between pilot and non-pilot group (pilot group: 185 (28%), non-pilot group: 131 (35%) p-value=0.018). According to the multivariate analysis, body mass index (BMI), diabetes, systolic blood pressure, triglycerides (TG), uric acid (UA), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), alanine aminotransferase (ALT) were a risk factor associated with MAFLD among the entire soldiers. When categorized into pilot and non-pilot group, risk factors were associated with BMI, diabetes, alcohol consumption, and ALT in the non-pilot group. In the pilot group, they were statistically associated with age, BMI, dyslipidemia, TG, UA, HDL and ALT. Among them, UA showed the largest difference between the non-pilot group and the test group (non-pilot group: 1.14 (95% CI: 0.80-1.62), pilot group: 1.80 (95% CI: 1.38-2.36)).

Conclusion

There was a difference in the prevalence of MAFLD between pilot and non-pilot group. In particular, UA could be used to predict MAFLD as a specific risk factor in pilots comparing with non-pilots.

Introduction

Although circulating tumor DNA (ctDNA) has shown promising results in monitoring response/relapse in pancreatic cancer patients, the limited availability of sensitive, cost-effective, and efficient molecular technologies for their detection has restricted its use. Here, we present a fast single-step methodology utilizing the amplification-refractory mutation system (ARMS) coupled with high-resolution melting analysis (HRMA) as a new method to evaluate KRAS mutations in tumor samples and ctDNA.

Aims & Methods

This is a prospective bicentric cohort study including pancreatic ductal adenocarcinoma cancer patients with tumor samples and liquid biopsies collected at diagnosis. Codon-12 KRAS mutations were tested by Sanger-Sequencing (SS) and G12D, G12V, G12R, G12C mutations were tested by ARMS/HRMA. The frequency of KRAS mutations by both techniques was evaluated. Progression-free survival and overall survival were also calculated.

Results

41 patients, 61% male, with median-age at diagnosis of 69 (IQR 62-76) years-old, 40% with metastatic disease at diagnosis were included. SS detected KRAS mutations in 23 (56%) tumor samples (G12D=12, G12V=7, G12R=2, G12C=2) and ARMS/HRMA in 33 (81%) (G12D=18, G12V=9, G12R=2, G12C=1, G12V/G12D=2, G12D/G12C=1), with a moderate concordance in mutation detection (kappa=0.48, p<0.001). Regarding liquid biopsies, no mutations were detected with SS technique, but ARMS/HRMA detected KRAS mutations in 7 patients (G12D=4, G12V=2, G12V/G12D=1), all of which were in agreement with mutations found in primary tumor. In non-operated patients, those with KRAS mutations detected in liquid biopsies showed a trend towards lower OS compared to patients with wildtype tumors (2 vs 10 months, HR 3.143, p=0.133).

Conclusion

The ARMS/HRMA method is a more effective means of detecting KRAS mutations in both PDAC tumor samples and liquid biopsies compared to SS, although its accuracy in liquid biopsies can be optimized. It might become a cost-effective tool to assess response to medical or surgical therapy as well as to detect early relapse. Further studies are required to validate these findings.