Introduction

Gastric linitis is a kind of adenocarcinoma that invades the stomach and is composed of separate cells. The predicted survival rate for this condition over a five-year period ranges from 3 to 10%. The excessive cell growth that characterizes gastric linitis also results in the formation of fibrous tissue, which makes the stomach wall thicker and less flexible. Consequently, mucous biopsies frequently do not provide useful information.

Aims & Methods

The aim of this study is to evaluate the diagnostic performance of echo-endoscopic biopsy puncture (EUS-FNB) in the diagnosis of gastric linitis.This study is an observational retrospective monocentric analysis conducted over a period of 4 years from January 2018 to December 2022. It includes all patients who underwent a parietal gastric and/or ganglionary puncture under echo endoscopic guidance using a 20G or 22G Procore® or Acquire® type 22G FNB needle. The purpose of the procedure was to investigate suspected cases of gastric linitis. The study is conducted at the University Hospital Centre in Marrakech, which serves as a tertiary care department and is a point of reference for all regional and provincial hospitals. The appearance of parietal gastric thickness, abdominal DMT, an infiltrated aspect of the stomach, folds, or gastric stenosis in high digestive endoscopy led to the suspicion of gastric linitis.The data was obtained from various sources, including hospital registers, patient medical records, the computerized system "Hosix" for morphological and anatomopathological data, and the collaboration of the medical and paramedical staff from the departments of gastroenterology, visceral surgery, and anatomopathology. The statistical analysis was conducted using SPSS version 22.0. Socio-demographic, clinical and para-clinical data were collected taking into account the global ethical rules relating to confidentiality and protection of patient-specific data.

Results

Out of 42 patients who performed biopsy puncture under high echo-endoscopy on suspicion of diagnosis, ten patients had gastric linitis. The diagnosis of gastric linitis was obtained by puncture in 90% of cases (9/10). Eight patients (80%) had previously undergone at least one oeso-gastro-duodenal fibroscopy with returning negative mucous biopsies. Six patients were diagnosed as early as 1st EEH while 3 others required a second series of biopsies. While the mucous biopsies were also unsuccessful, echo-guided biopsy allowed the diagnosis of other more serious diseases in 43% of cases (n = 18/42) including gastric metastases of a breast cancer (n=2), other gastric adenocarcinomas of the intestinal type (N=8), and cases of T-type gastric lymphoma in one case and MALT type in 2 cases.

Conclusion

In case of suspicion of gastric linitis, guided biopsy puncture under echo-endoscopy is a cost-effective approach in 90% of cases, without noticeable side effects. It should be considered the procedure of choice for early diagnosis of gastric linitis when mucous biopsies return negative.

Introduction

Informed consent (IC) serves as the ethical foundation for all medical interventions, empowering patients to make informed, autonomous decisions while safeguarding clinicians. Barriers such as limited health literacy and document complexity may hinder comprehension^1,2. This study evaluated the comprehensibility, readability, and effectiveness of the documents provided for IC and instructions for endoscopic procedures.

Aims & Methods

Outpatients undergoing endoscopic procedures completed a questionnaire assessing their understanding of IC, preparation instructions, and adherence to guidelines. Patient confidence and document comprehensibility were assessed through self-reported scales. Readability was assessed using Flesch Reading Ease score adapted for portuguese (FRE-PT)³.

Results

Among 186 participants (mean age: 58.1 ± 16.1 years), 76.9% reported full-extent reading of the provided instructions and IC document. Patients with primary education (≤4th grade) were less likely to read the documents fully (59.2% vs. 83.2%, p < 0.001) and were independently associated with the need for additional assistance (OR 5.65, 95% CI: 1.92 - 16.68, p = 0.002). Full-extent reading was independently associated with greater risk awareness (OR 5.52, 95% CI: 2.37 - 11.55, p < 0.001), reduced need for additional assistance (OR 0.22, 95% CI: 0.09 - 0.51, p < 0.001), and higher compliance with medication guidelines (75.7% vs. 45.8%, OR 3.42, 95% CI: 1.28 - 9.20, p = 0.015). Patients with primary education rated document’s comprehensibility lower (median:8, IQR 7-10) compared to those with higher education (median: 10, IQR 8 - 10, p < 0.001) and reported lower levels of confidence and preparation for the procedure (median: 8, IQR 7 - 10 vs. median: 9, IQR 8 - 10; p = 0.018). Outcomes did not differ significantly between patients aged 65 years or older compared to younger patients. FRE-PT scores classified readability as ‘’very difficult’’ for both upper endoscopy (20.87) and colonoscopy (26.00).

Conclusion

Full-extent reading IC and instruction documents reduces the need for assistance, improves compliance with pre-procedural measures, risk awareness and patient confidence. However, the document’s complexity and difficult readability disproportionately challenge and discourage patients with limited education. Future research should explore strategies to foster more equitable informed decision-making.

References

1. Protheroe J, Rowlands G. Matching clinical information with levels of patient health literacy. Nurs Manag (Harrow). 2013;20(3):20-21. doi:10.7748/nm2013.06.20.3.20.e1095
2. Ley R, Forio T. The use of readability formulas in health care. Psychol Health Med. 1996;1(1):7-28.
3. Martins TBF, Ghiraldelo CM, Nunes MGV, Oliveira Junior ON. Readability formulas applied to textbooks in Brazilian Portuguese. 1996.

Introduction

Metabolic dysfunction-associated fatty liver disease (MAFLD) has become the most common chronic liver disease in recent years. However, medications to improve MAFLD has no standard. Several potential agents have been widely investigated for the treatment of MAFLD. Pemafibrate, a selective peroxisome proliferator-activated receptor-α modulator, has been reported to improve dyslipidemia. Sodium-glucose cotransporter-2 inhibitor (SGLT2i) is an oral antidiabetes drug that promotes glucose excretion into the urine. These medications have potential therapeutic effects on MAFLD.

Aims & Methods

This retrospective study aimed to evaluate the effects of long-term administration of pemafibrate plus SGLT2i in patients with dyslipidemia and type 2 diabetes complicated by MAFLD. Transient elastography (FiboScan; Echosens, Paris, France) was used for liver stiffness measurement (LSM) and assessment of the controlled attenuation parameter (CAP). In total, 594 patients with dyslipidemia and type 2 diabetes complicated by MAFLD started pemafibrate plus SGLT2i treatment between 2019 and 2020 at our hospital. Pre- and post-treatment transient elastography data were compared.

Results

Following 3 years of pemafibrate plus SGLT2i treatment, the median LSM significantly decreased from 10.1 kPa to 6.4 kPa (P < 0.001) and the median CAP significantly decreased from 321 dB/m to 219 dB/m (P < 0.001), in spite of no significant reductions of the studied patients’ weight. Moreover, serum parameters, including hemoglobin A1c, alanine aminotransferase, and gamma-glutamyl transferase, significantly decreased over the study period.

Conclusion

The findings of our study confirm that long-term administration of pemafibrate plus SGLT2i can improve hepatic fibrosis by ameliorating hepatic steatosis and inflammation in patients with dyslipidemia and type 2 diabetes complicated by MAFLD.

References

Castera L, Forns X, Alberti A. Non-invasive evaluation of liver fibrosis using transient elastography. J Hepatol. 2008; 48(5): 835-847.
Yamashita S, Masuda D, Matsuzawa Y. Clinical Applications of a Novel Selective PPARα Modulator, Pemafibrate, in Dyslipidemia and Metabolic Diseases. J Atheroscler Thromb. 2019; 26(5): 389-402.
Mantovani A, Petracca G, Csermely A, et al. Sodium-Glucose Cotransporter-2 Inhibitors for Treatment of Nonalcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trials. Metabolites. 2020; 11(1): 22.
Murakami K, Sasaki Y, Asahiyama M, et al. Selective PPARα Modulator Pemafibrate and Sodium-Glucose Cotransporter 2 Inhibitor Tofogliflozin Combination Treatment Improved Histopathology in Experimental Mice Model of Non-Alcoholic Steatohepatitis. Cells. 2022;11(4):720.

Clinical Case Summary

Introduction: Ulcerative colitis (UC) is a chronic inflammatory disease characterized by remitting and relapsing patterns, necessitating multifaceted therapeutic interventions, among which mesalazine, or 5-aminosalicylic acid (5-ASA), is prominently utilized. Despite its typically favorable tolerability profile, mesalazine may occasionally precipitate severe adverse events, such as myocarditis.
Case presentation: A 46-year-old male recently diagnosed with UC presented with a moderate UC flare-up and was initiated on 5-ASA therapy upon admission.
Within a span of two days following initiation of oral therapy, he developed acute chest pain, palpitations, dyspnea, and desaturation, necessitating intensive care due to cardiogenic shock.
Paraclinical assessments revealed elevated troponin levels, along with electrocardiographic and echocardiographic abnormalities, including left ventricular dysfunction and reduced ejection fraction.
Discontinuation of mesalazine resulted in symptom improvement and reduction of cardiac markers. Subsequent evaluations demonstrated a recovery in cardiac function, establishing a causal relationship between myocarditis and the administration of 5-ASA. Consequently, a therapeutic switch to mercaptopurine was instituted.
Conclusion: This case underscores the infrequent yet significant hazard of mesalazine-triggered myocarditis, emphasizing the critical necessity for vigilant patient monitoring during this therapy and prompt consideration of alternative therapeutic options in the presence of severe cardiac complications.

Introduction

Inflammatory Bowel Diseases (IBD) are chronic inflammatory disorders characterized by alterations of acute relapses and remission. The past decades have brought substantial advances in the pharmacological management of IBD by a wide range of medicines. However, the sustained efficacy of the currently available anti-inflammatory therapies is still far from optimal. Therefore, the development of novel therapies represents a major unmet clinical need in this field. Recently, the enrichment of the coagulation pathway genes and among these, Plasminogen activator inhibitor 1 (PAI-1) was described in IBD, whereas PAI-1 emerged as a link between the epithelium and inflammation. Moreover, the genetic deletion of PAI-1 prevented the severity of experimental colitis in mice.

Aims & Methods

Based on these, we aimed to develop and test novel PAI-1 inhibitors for the treatment of IBD.
The novel, amino acid-based PAI-1 inhibitor, LDN-071 was synthesized by the A³SMO^® platform. The inhibitory potential and cytotoxicity effects of the peptide were determined by in vitro assays. Acute and chronic colitis was induced in mice with DSS and 10 mg/bwkg LDN-071 was administered per os. The changes of body weight, spleen weight, and colon length were measured. Haematoxylin eosin (HE) and Periodic acid-Schiff (PAS) staining were performed for histology. ELISA and qRT-PCR measurements were applied to analyze the cytokine expressions. Hydroxyproline assay was used to quantify the mucosal collagen deposition. In vivo, the toxicity of LDN-071 was determined in mice. Human colon organoid and fibroblast (FB) cell cultures were generated from IBD patients and the effects of LDN-071 were observed.

Results

LDN-071 significantly inhibited PAI-1 in vitro without decreasing the cell viability in a concentration range of 1µM-1mM. In the acute mice model, the administration of 10 mg/bwkg LDN-071 in the DSS-treated mice prevented the body weight loss, the development of bloody diarrhea, the decrease of colon length, and the increase of the spleen weight, which were displayed by the DSS+vehicle-treated animals. The histological analysis of the colon revealed that DSS treatment induced severe transmural inflammation, ulceration, loss of crypt structures, and goblet cell depletion. Importantly, all these parameters were significantly ameliorated by the administration of 10 mg/bwkg LDN-071 in the acute and chronic models as well. Additionally, mucosal gene and protein expressions of TNF-α, IL-1β, and IL-6 were significantly decreased by PAI-1 inhibition in the acute phase. Besides, the LDN-071 treatment significantly reduced the inflammation, epithelial erosion, and fibrosis caused by chronic administration of DSS. However, the collagen deposition was significantly lower in the PAI-1-inhibited DSS mice. Importantly, no signs of toxicity were observed in mice exposed to 100 mg/bwkg LDN-071 for 7 days. In our in vitro models, the PAI-1 inhibition reduced the protein level and gene expression of pro-inflammatory cytokines in human colon organoid of IBD patient. Moreover, the gene expression of fibrosis-related genes significantly decreased after the LDN-071 treatment in IBD patients-derived human FB cell culture.

Conclusion

Our results showed that LDN-071, a novel amino acid-based inhibitor of PAI-1, significantly ameliorated the severity of acute and chronic colitis in mice. However, the LDN-071 reduced the expression of inflammation- and fibrosis-related genes and proteins in vitro human models. We propose that the inhibition of PAI-1 could be a potential novel therapeutic strategy in IBD.

Disclosure

LDN-071 PAI-1 inhibitor is owned by Ladon Therapeutics Ltd.