Inflammatory Bowel Diseases (IBD) still represent a significant medical challenge. The course of IBD is characterized by the development of fibrotic, inflammatory, or dysplastic lesions over time. Recent advancements in operative endoscopy have introduced new strategies to address these issues. Inflammatory and fibrotic strictures pose a challenge for clinicians and represent a surgical risk. Endoscopic treatments include dilation, stent placement, and electroincisional techniques. Moreover, endoscopic approaches can also be considered in the management of IBD-related surgical complications. Addressing colorectal dysplastic lesions is a crucial concern, and several resection endoscopic techniques are available, including endoscopic mucosal resection and endoscopic submucosal dissection. This review aimed to summarize the pros and cons of advanced therapeutic endoscopic approaches in the management of IBD.

Clostridioides difficile infection (CDI) is associated with significant morbidity and mortality and carries a high risk of recurrence. Given the substantial healthcare burden and the evolving nature of CDI, understanding the role of emerging treatment strategies is essential. While oral vancomycin remains a mainstay of CDI treatment, the past decade has brought several notable advances in agents and practices that may be used for CDI treatment and prevention. Fidaxomicin or vancomycin are now recommended for an initial episode of CDI, with several guidelines giving preference to fidaxomicin based on its demonstrated ability to reduce recurrent CDI. Promising developments have emerged regarding the use of fecal microbiota-based therapies in the management of CDI, including conventional fecal microbiota transplantation and the approved live biotherapeutic products, Rebyota and Vowst. These therapies help restore the microbiota of the colon to treat severe CDI and prevent recurrence in select patients. Several strategies have emerged to prevent recurrent CDI, including bezlotoxumab, a single-dose, weight-based IgG1 monoclonal antibody that may be given to patients at high risk of recurrence. Additional pipeline therapies, such as vaccines, beta-lactamases, and bacteriophages, may provide future opportunities for CDI management. This narrative review aimed to summarize societal guideline recommendations for CDI management, describe the evidence for key therapies used in CDI treatment, and review recent updates on emerging treatment modalities.

Molecular testing has emerged as a valuable tool for stratifying cytologically indeterminate thyroid nodules (ITNs), with Harvey rat sarcoma viral oncogene homolog/neuroblastoma RAS viral oncogene homolog (HRAS/NRAS) mutations being among the most prevalent molecular alterations. The study aimed to evaluate the malignancy risk of ITNs with these mutations.

We conducted a retrospective study involving ITNs (Bethesda category III and IV) that underwent ThyroSeq testing between February 2016 and January 2022. A smaller subset of ITNs also underwent Afirma testing. We specifically identified nodules with HRAS/NRAS mutations and collected radiological, clinical, histological, and follow-up data.

Our analysis identified 45 ITNs with NRAS (29 cases) and HRAS (15 cases) mutations. Of the 29 nodules with NRAS mutations, 25 underwent surgical treatment (14 total thyroidectomies and 11 hemithyroidectomies), resulting in a surgical resection rate of approximately 86%. Among the resected nodules, six were malignant, yielding a calculated risk of malignancy (ROM) ranging from 20.6% to 25%. Three of these malignant nodules were managed with total thyroidectomy, while the other three underwent hemithyroidectomy. During a follow-up period of 43.8 months for total thyroidectomy and 32.9 months for hemithyroidectomy, no recurrence or metastasis was detected among the patients. Among the four nodules treated conservatively, three remained stable, with an average follow-up duration of 34.7 months, while one patient was lost to follow-up. Regarding HRAS mutations, 15 nodules were identified, with 12 of them undergoing surgical treatment (six total thyroidectomies and 6 hemithyroidectomies), resulting in an 80% surgical resection rate. Two of the resected nodules were malignant, with a calculated ROM of 13.3% to 16.7%. Both malignant nodules were managed with total thyroidectomy, and during a follow-up period of 37.9 months, no recurrence or metastasis occurred. Of the three nodules managed conservatively, all remained stable, with an average follow-up duration of 31.1 months.

The ROM for nodules with NRAS (20.6–25%) or HRAS (13.3–16.7%) mutations was found to be low. Therefore, before opting for total thyroidectomy, conservative management, including limited resection, should be considered as a viable alternative.

Erosive Esophagitis (EE) is the most common complication of gastroesophageal reflux disease. Patients with EE can be asymptomatic or present with severe symptoms such as dysphagia and gastrointestinal bleeding. Approximately 10-15% of patients with EE have refractory disease. Optimal management of EE requires understanding its pathophysiology, clinical presentation, and available evaluation and treatment modalities. While pharmacologic treatment of EE is often successful, procedural options such as surgery and endoscopic therapy may be necessary. This article presents an evidence-based and pragmatic approach to the management of EE, the most common complication of gastroesophageal reflux disease.

The activation of the Kirsten RAS (KRAS) oncogene is one of the factors responsible for the transition from intermediate adenoma to carcinoma in the colon. Approximately 30% to 60% of mutations in colorectal cancer (CRC) occur in the hotspot codons 12 and 13 of exon 1 and codon 61 of exon 2. This study aimed to characterize mutations of the KRAS gene among Filipinos with CRC.

Paired frozen normal and tumor tissues from 35 CRC patients who underwent surgical resection were included. Genomic DNA was extracted, and all five coding exons were amplified by polymerase chain reaction, followed by mutation screening using denaturing high-performance liquid chromatography and DNA sequencing.

From sequencing, 18/35 (51%) samples showed mutations in exon 1 (A11R, G13C, L19W, and silent mutation L23), exon 2 (D54H), and codon 4B (silent mutation D173). Nine mutations could be considered pathogenic as they occurred within the conserved region, potentially contributing to the oncogenic potential of KRAS. Eight of these mutations were also found outside the hotspot region of the KRAS gene. Mutations were significantly associated with tumor stage III (p = 0.007) but not with other clinical parameters or survival.

This study characterizes KRAS mutations in Filipino patients with CRC, suggesting a possible difference in their cancer genetic profiles. Additionally, the use of easily accessible mutation screening techniques, such as denaturing high-performance liquid chromatography, may help increase reports of mutational profiles in Southeast Asian populations.

Early determination of prognosis in patients with acute-on-chronic liver failure (ACLF) is crucial for optimizing treatment options and liver allocation. This study aimed to identify risk factors associated with ACLF and to develop new prognostic models that accurately predict patient outcomes.

We retrospectively selected 1,952 hospitalized patients diagnosed with ACLF between January 2010 and June 2018. This cohort was used to develop new prognostic scores, which were subsequently validated in external groups.

The study included 1,386 ACLF patients and identified six independent predictors of 28-day mortality through multivariate analysis (all p < 0.05). The new score, based on a multivariate regression model, demonstrated superior predictive accuracy for both 28-day and 90-day mortalities, with Areas under the ROC curves of 0.863 and 0.853, respectively (all p < 0.05). This score can be used to stratify the risk of mortality among ACLF patients with ACLF, showing a significant difference in survival between patients categorized by the cut-off value (log-rank (Mantel–Cox) χ2 = 487.574 and 606.441, p = 0.000). Additionally, the new model exhibited good robustness in two external cohorts.

This study presents a refined prognostic model, the Model for end-stage liver disease-complication score, which accurately predicts short-term mortality in ACLF patients. This model offers a new perspective and tool for improved clinical decision-making and short-term prognostic assessment in ACLF patients.

Chlorella vulgaris is a green, photosynthetic microalga in the phylum Chlorophyta. The goal of our study was to perform a bioinformatics analysis of Photosystem I P700 chlorophyll a apoprotein A2, one of its photosynthesis-related proteins, and to hunt for potent bioactive peptides.

To generate peptides and estimate the safety and efficacy of each bioactive peptide, we employed the tools BIOPEP-UWM™, PeptideRanker, DBAASP, and ToxinPred. PepDraw was used to understand the physicochemical properties and primary chemical structures of the selected bioactive peptides.

The liberated peptides exhibit up to 17 distinct bioactivities, as shown by the in silico digestion of the protein using several proteolytic enzymes. The peptides with bioactivities are listed as angiotensin-converting enzyme inhibitor, dipeptidyl peptidase IV inhibitor, dipeptidyl peptidase III inhibitor, antioxidative, renin inhibitor, glucose uptake stimulator, neuropeptide regulator (regulating stomach mucosal membrane activity and ion flow), antithrombotic, anti-amnestic, CaMPDE inhibitor, activators of ubiquitin-mediated proteolysis, alpha-glucosidase inhibitor, immunomodulating, calcium-binding, antibacterial, anti-inflammatory, and hypotensive agent. Using the Database of Antimicrobial Activity and Structure of Peptides (DBAASP) prediction method, the antibacterial activity of the released peptides was predicted, highlighting the existence of potent antibacterial peptides. An examination of their physicochemical properties revealed that most peptides are low molecular weight, mildly acidic, and moderately water-soluble. To further establish the non-toxicity profile of the released peptides (sequence length > 3), a ToxinPred analysis was performed, which revealed that most of the peptides are non-toxic. According to the allergenicity analysis, most of the top-ranked peptides are likely non-allergenic.

Thus, our study reveals a less labor-intensive method for discovering new therapeutic targets derived from C. vulgaris, which hold both pharmacological and medical significance.

Glutathione peroxidase 4 (GPX4) is a key factor in ferroptosis, which is involved in ischemia-reperfusion injury. However, little is known about its role in hepatic ischemia-reperfusion injury (HIRI). This study aimed to investigate the role of GPX4 methylation in ferroptosis during HIRI.

For the in vitro experiments, an oxygen and glucose deprivation cell model was established. For the in vivo experiments, an ischemia-reperfusion model was created by subjecting mice to simulated HIRI. Ferroptosis occurrence, GPX4 promoter methylation, and global methylation levels were then assessed.

Ferroptosis was observed in oxygen and glucose deprivation, characterized by a significant decrease in cellular viability (P < 0.05), an increase in lipid peroxidation (P < 0.01), iron overload (P < 0.05), and down-regulation of GPX4 (P < 0.05). This ferroptosis was exacerbated by GPX4 knockdown (P < 0.01) and mitigated by exogenous glutathione (P < 0.01). Similarly, ferroptosis was evident in mice subjected to HIRI, with a down-regulation of GPX4 mRNA and protein expression (all P < 0.01), and an upregulation of acyl-CoA synthetase long-chain family member 4 mRNA and protein (all P < 0.01), as well as prostaglandin-endoperoxide synthase 2 mRNA and protein expression (all P < 0.05). Methylation levels increased, evidenced by upregulation of DNA methylation transferase expression (P < 0.05) and down-regulation of Ten-eleven translocation family demethylases (P < 0.01), along with an upregulation of GPX4 promoter methylation.

Ferroptosis may be the primary mode of cell death in hepatocytes following ischemia-reperfusion injury. The methylation of the GPX4 promoter and elevated levels of global hepatic methylation are involved in the regulation of ferroptosis.

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists are increasingly used in the management of type 2 diabetes mellitus and obesity due to their ability to stimulate insulin secretion, delay gastric emptying, and suppress appetite. The combination of GLP-1 and GIP agonists improves glycemic control and promotes weight loss. However, the introduction of these novel therapies has raised safety concerns, including the risk of cholestatic hepatitis. We report a case of a patient with obesity who was prescribed a GLP-1/GIP dual-receptor agonist as part of his treatment regimen. Importantly, both before the initiation of this therapy and during the course of treatment, the patient was not taking any other medications. Shortly after receiving four doses of the therapy, the patient developed symptoms of severe cholestatic hepatitis, including jaundice and elevated liver enzyme levels. During hospitalization, no alternative causes for the condition were identified, and a liver biopsy confirmed the diagnosis of drug-induced cholestatic hepatitis. This is the first recorded case of cholestatic hepatitis induced by a GLP-1/GIP dual agonist, and it aimed to raise global awareness of this potential side effect.

The World Health Organization System for Reporting Pancreaticobiliary Cytopathology introduces a seven-tier category system to standardize terminology and nomenclature. This system includes the following categories: Insufficient/non-diagnostic, benign/negative for malignancy, atypia, pancreaticobiliary neoplasm low-risk/grade, pancreaticobiliary neoplasm high-risk/grade, suspicious for malignancy, and malignant categories. Adopting a standardized reporting scheme facilitates consistent diagnostic criteria among pathologists, thereby reducing report variability and enhancing communication with the clinical team for optimal patient management. The report also highlights the role of critical ancillary tests in improving diagnostic accuracy for pancreatic lesions and discusses practical approaches to managing solid and cystic pancreatic lesions.