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World Journal of Gastrointestinal... May 2024Most endoscopic anti-reflux interventions for gastroesophageal reflux disease (GERD) management are technically challenging to practice with inadequate data to support...
BACKGROUND
Most endoscopic anti-reflux interventions for gastroesophageal reflux disease (GERD) management are technically challenging to practice with inadequate data to support it utility. Therefore, this study was carried to evaluate the effectiveness and safety newer endoscopic full-thickness fundoplication (EFTP) device along with Argon Plasma Coagulation to treat individuals with GERD.
AIM
To evaluate the effectiveness and safety newer EFTP device along with Argon Plasma Coagulation to treat individuals with GERD.
METHODS
This study was a single-center comparative analysis conducted on patients treated at a Noble Institute of Gastroenterology, Ahmedabad, hospital between 2020 and 2022. The research aimed to retrospectively analyze patient data on GERD symptoms and proton pump inhibitor (PPI) dependence who underwent EFTP using the GERD-X system along with argon plasma coagulation (APC). The primary endpoint was the mean change in the total gastroesophageal reflux disease health-related quality of life (GERD-HRQL) score compared to the baseline measurement at the 3-month follow-up. Secondary endpoints encompassed enhancements in the overall GERD-HRQL score, improvements in GERD symptom scores at the 3 and changes in PPI usage at the 3 and 12-month time points.
RESULTS
In this study, patients most were in Hill Class II, and over half had ineffective esophageal motility. Following the EFTP procedure, there were significant improvements in heartburn and regurgitation scores, as well as GERD-HRQL scores ( < 0.001). PPI use significantly decreased, with 82.6% not needing PPIs or prokinetics at end of 1 year. No significant adverse events related to the procedures were observed in either group.
CONCLUSION
The EFTP along with APC procedure shows promise in addressing GERD symptoms and improving patients' quality of life, particularly for suitable candidates. Moreover, the application of a lone clip with APC yielded superior outcomes and exhibited greater cost-effectiveness.
PubMed: 38813575
DOI: 10.4253/wjge.v16.i5.250 -
Heliyon May 2024In this study, the proton-induced reactions of Zn and Ga aimed at generating Ga were simulated and modeled using Talys code and neural network software. In the first...
In this study, the proton-induced reactions of Zn and Ga aimed at generating Ga were simulated and modeled using Talys code and neural network software. In the first step, both targets were simulated under different proton energies and at different bombardments times to generate a total of six thousand data. Then, the obtained data from the Talys, including the various cross-sections, contaminations, the main product i.e. Ga, and other options were completely saved in the output file. Afterwards, the inputs of the neural network were selected from the output of the Talys by analyzing and considering most of the key features. A total of four inputs, two of which are different energies related to the reaction, the other is the process sequence and the fourth input is the bombardment time, were recognized as suitable inputs and the model was trained differently depending on the type of target. The selected model was a feed-forward neural network with 5 nodes in a middle layer, which was able to estimate the output of Talys code by changing the input parameters with extremely high accuracy. Two different models including the main model for estimating the output of the main sample (product) and the sub-model for estimating process pollution or impurity were trained, and then the trained model was tested on the deduced process data. The implementation results fully demonstrated the high accuracy of the method. The neural network model is much easier to implement than the Talys code, and its execution speed is very high. In addition, it can be used appropriately as a system alternative for optimization and different structures in medical and biological engineering.
PubMed: 38813197
DOI: 10.1016/j.heliyon.2024.e31499 -
World Journal of Gastroenterology May 2024Difficulty in obtaining tetracycline, increased adverse reactions, and relatively complicated medication methods have limited the clinical application of the classic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Difficulty in obtaining tetracycline, increased adverse reactions, and relatively complicated medication methods have limited the clinical application of the classic bismuth quadruple therapy. Therefore, the search for new alternative drugs has become one of the research hotspots. In recent years, minocycline, as a semisynthetic tetracycline, has demonstrated good potential for eradicating () infection, but the systematic evaluation of its role remains lacking.
AIM
To explore the efficacy, safety, and compliance of minocycline in eradicating infection.
METHODS
We comprehensively retrieved the electronic databases of PubMed, Embase, Web of Science, China National Knowledge Infrastructure, SinoMed, and Wanfang database as of October 30, 2023, and finally included 22 research reports on eradication with minocycline-containing regimens as per the inclusion and exclusion criteria. The eradication rates of were calculated using a fixed or a random effect model, and the heterogeneity and publication bias of the studies were measured.
RESULTS
The single-arm meta-analysis revealed that the minocycline-containing regimens achieved good overall eradication rates, reaching 82.3% [95% confidence interval (CI): 79.7%-85.1%] in the intention-to-treat analysis and 90.0% (95%CI: 87.7%-92.4%) in the per-protocol analysis. The overall safety and compliance of the minocycline-containing regimens were good, demonstrating an overall incidence of adverse reactions of 36.5% (95%CI: 31.5%-42.2%). Further by traditional meta-analysis, the results showed that the minocycline-containing regimens were not statistically different from other commonly used eradication regimens in eradication rate and incidence of adverse effects. Most of the adverse reactions were mild to moderate and well-tolerated, and dizziness was relatively prominent in the minocycline-containing regimens (16%).
CONCLUSION
The minocycline-containing regimens demonstrated good efficacy, safety, and compliance in eradication. Minocycline has good potential to replace tetracycline for eradicating infection.
Topics: Humans; Minocycline; Helicobacter Infections; Helicobacter pylori; Anti-Bacterial Agents; Drug Therapy, Combination; Treatment Outcome; Proton Pump Inhibitors; Medication Adherence
PubMed: 38813048
DOI: 10.3748/wjg.v30.i17.2354 -
Therapeutic Advances in Gastroenterology 2024Eosinophilic esophagitis (EoE) is recognized as a chronic type 2 inflammatory disease characterized by the eosinophilic infiltration of the esophageal tissue, posing a... (Review)
Review
BACKGROUND
Eosinophilic esophagitis (EoE) is recognized as a chronic type 2 inflammatory disease characterized by the eosinophilic infiltration of the esophageal tissue, posing a significant disease burden and highlighting the necessity for novel management strategies to address unmet clinical needs.
OBJECTIVES
To critically evaluate the existing literature on the epidemiology and management of EoE, identify evidence gaps, and assess the efficacy of current and emerging treatment modalities.
DESIGN
An extensive literature review was conducted, focusing on the epidemiological trends, diagnostic challenges, and therapeutic interventions for EoE. This was complemented by a survey among physicians and consultations with a scientific expert panel, including a patient's association (ESEO Italia), to enrich the study findings.
DATA SOURCES AND METHODS
The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, scrutinizing epidemiological studies and management research to compile comprehensive insights into the disease's landscape. The physician survey and expert panel discussions aimed to bridge identified evidence gaps.
RESULTS
The review included 59 epidemiological and 51 management studies, uncovering variable incidence and prevalence rates of EoE globally, with an estimated diagnosed prevalence of 41 per 100,000 in Italy. Diagnostic challenges were identified, including nonspecific symptoms and the lack of definitive biomarkers, which complicate the use of endoscopy. Treatment options such as elimination diets, proton-pump inhibitors, and swallowed corticosteroids were found to have varying success rates, while Dupilumab, an emerging therapy targeting interleukin (IL)-4 and IL-13, shows promise.
CONCLUSION
Despite advancements in understanding and managing EoE, significant unmet clinical needs remain, particularly in biomarker identification, therapy personalization, and cost-effectiveness evaluation. A comprehensive, multidimensional approach to patient management is required, emphasizing the importance of early symptom recognition, accurate diagnosis, and tailored treatment strategies. Dupilumab offers potential as a novel treatment, underscoring the need for future research to explore the economic and social dimensions of EoE care pathways.
PubMed: 38812705
DOI: 10.1177/17562848241249570 -
BMC Pediatrics May 2024To evaluate the effects of local radiotherapy (RT) on growth, we evaluated the chronological growth profiles and vertebral features of children with high-risk...
BACKGROUND
To evaluate the effects of local radiotherapy (RT) on growth, we evaluated the chronological growth profiles and vertebral features of children with high-risk neuroblastoma.
METHODS
Thirty-eight children who received local photon or proton beam therapy to the abdomen or retroperitoneum between January 2014 and September 2019 were included. Simple radiography of the thoracolumbar spine was performed before and every year after RT. The height and vertical length of the irradiated vertebral bodies (VBs) compared with the unirradiated VBs (vertebral body ratio, VBR) were analyzed using the linear mixed model. Shape feature analysis was performed to compare the irradiated and unirradiated vertebrae.
RESULTS
The follow-up was a median of 53.5 months (range, 21-81 months) after RT. A decline in height z-scores was mainly found in the early phase after treatment. In the linear mixed model with height, the initial height (fixed, p < 0.001), sex (time interaction, p = 0.008), endocrine dysfunction (time interaction, 0.019), and age at diagnosis (fixed and time interaction, both p = 0.002) were significant. Unlike the trend in height, the change in VBR (ΔVBR) decreased gradually (p < 0.001). The ΔVBR in the group that received more than 30 Gy decreased more than in the group that received smaller doses. In the shape feature analysis, the irradiated VBs changed to a more irregular surface that were neither round nor rectangular.
CONCLUSION
The irradiated VBs in children were gradually restricted compared to the unirradiated VBs in long-term follow-up, and higher RT doses were significantly affected. Radiation-induced irregular features of VBs were observed.
Topics: Humans; Neuroblastoma; Male; Female; Child, Preschool; Child; Infant; Follow-Up Studies; Retrospective Studies; Body Height; Thoracic Vertebrae; Lumbar Vertebrae; Abdominal Neoplasms; Vertebral Body; Proton Therapy; Retroperitoneal Neoplasms
PubMed: 38811872
DOI: 10.1186/s12887-024-04813-z -
BMC Gastroenterology May 2024Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such...
BACKGROUND
Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such as gastric polyps and enterochromaffin-like cell hyperplasia. Current research indicates that the abovementioned adverse reactions are mainly related to hypergastrinemia. We investigated whether low-frequency administration of omeprazole could effectively repair aspirin-induced mucosal damage and reduce the increase in gastrin levels associated with long-term use of PPIs.
METHODS
Sprague‒Dawley rats were divided into four treatment groups: daily aspirin, daily aspirin and omeprazole once every day (qd), daily aspirin and omeprazole once every other day (qod), and daily aspirin and omeprazole once every three days (1/d3). After 15 days of feeding, blood samples were collected, and the stomachs of sacrificed rats were subjected to macroscopic, histological, and immunohistochemical studies. Moreover, in clinical practice, patients with peptic ulcers caused by aspirin took a standard dose of omeprazole (20 mg) every other day. Two months later, gastroscopy was performed to examine the healing of the ulcers.
RESULTS
Both the omeprazole qd and omeprazole qod administrations effectively prevented aspirin-induced gastric peptic ulcers, with no significant difference between the two groups in the inhibition of parietal cell secretion of gastric acid and cell apoptosis. However, omeprazole 1/d3 failed to completely prevent aspirin-induced gastric mucosal injury. Notably, the gastrin levels, cell proliferation ability and cholecystokinin B receptor expression of the omeprazole qd group were significantly higher than those of the omeprazole qod group. In clinical work, patients with peptic ulcers caused by aspirin were given a standard dose of omeprazole every other day, and their ulcers healed after 2 months, as observed by gastroscopy.
CONCLUSIONS
Omeprazole administration once every other day can effectively prevent aspirin-induced peptic ulcers and reduce hypergastrinemia, which may reduce the long-term adverse effects of PPI treatment.
Topics: Animals; Aspirin; Omeprazole; Rats, Sprague-Dawley; Proton Pump Inhibitors; Gastric Mucosa; Gastrins; Male; Rats; Drug Administration Schedule; Humans; Peptic Ulcer; Intestinal Mucosa; Stomach Ulcer
PubMed: 38811868
DOI: 10.1186/s12876-024-03265-0 -
Bone Research May 2024Wnt/β-catenin signaling is critical for various cellular processes in multiple cell types, including osteoblast (OB) differentiation and function. Exactly how...
Wnt/β-catenin signaling is critical for various cellular processes in multiple cell types, including osteoblast (OB) differentiation and function. Exactly how Wnt/β-catenin signaling is regulated in OBs remain elusive. ATP6AP2, an accessory subunit of V-ATPase, plays important roles in multiple cell types/organs and multiple signaling pathways. However, little is known whether and how ATP6AP2 in OBs regulates Wnt/β-catenin signaling and bone formation. Here we provide evidence for ATP6AP2 in the OB-lineage cells to promote OB-mediated bone formation and bone homeostasis selectively in the trabecular bone regions. Conditionally knocking out (CKO) ATP6AP2 in the OB-lineage cells (Atp6ap2) reduced trabecular, but not cortical, bone formation and bone mass. Proteomic and cellular biochemical studies revealed that LRP6 and N-cadherin were reduced in ATP6AP2-KO BMSCs and OBs, but not osteocytes. Additional in vitro and in vivo studies revealed impaired β-catenin signaling in ATP6AP2-KO BMSCs and OBs, but not osteocytes, under both basal and Wnt stimulated conditions, although LRP5 was decreased in ATP6AP2-KO osteocytes, but not BMSCs. Further cell biological studies uncovered that osteoblastic ATP6AP2 is not required for Wnt3a suppression of β-catenin phosphorylation, but necessary for LRP6/β-catenin and N-cadherin/β-catenin protein complex distribution at the cell membrane, thus preventing their degradation. Expression of active β-catenin diminished the OB differentiation deficit in ATP6AP2-KO BMSCs. Taken together, these results support the view for ATP6AP2 as a critical regulator of both LRP6 and N-cadherin protein trafficking and stability, and thus regulating β-catenin levels, demonstrating an un-recognized function of osteoblastic ATP6AP2 in promoting Wnt/LRP6/β-catenin signaling and trabecular bone formation.
Topics: Animals; Low Density Lipoprotein Receptor-Related Protein-6; Wnt Signaling Pathway; beta Catenin; Mice, Knockout; Osteoblasts; Osteogenesis; Mice; Vacuolar Proton-Translocating ATPases; Protein Transport; Cell Differentiation; Osteocytes; Prorenin Receptor
PubMed: 38811544
DOI: 10.1038/s41413-024-00335-7 -
Endocrine Journal May 2024The beneficial effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in people with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver...
Prolonged impacts of sodium glucose cotransporter-2 inhibitors on metabolic dysfunction-associated steatotic liver disease in type 2 diabetes: a retrospective analysis through magnetic resonance imaging.
The beneficial effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in people with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD) have been suggested in several reports based on serological markers, imaging data, and histopathology associated with steatotic liver disease. However, evidence regarding their long-term effects is currently insufficient. In this retrospective observational study, 34 people with T2D and MASLD, treated with SGLT2 inhibitors, were examined by proton density fat fraction derived by magnetic resonance imaging (MRI-PDFF) and other clinical data before, one year after the treatment. Furthermore, 22 of 34 participants underwent MRI-PDFF five years after SGLT2 inhibitors were initiated. HbA1c decreased from 8.9 ± 1.8% to 7.8 ± 1.0% at 1 year (p = 0.006) and 8.0 ± 1.1% at 5 years (p = 0.122). Body weight and fat mass significantly reduced from baseline to 1 and 5 year(s), respectively. MRI-PDFF significantly decreased from 15.3 ± 7.8% at baseline to 11.9 ± 7.6% (p = 0.001) at 1 year and further decreased to 11.3 ± 5.7% (p = 0.013) at 5 years. Thus, a 5-year observation demonstrated that SGLT2 inhibitors have beneficial effects on liver steatosis in people with T2D and MASLD.
PubMed: 38811192
DOI: 10.1507/endocrj.EJ24-0005 -
Korean Journal of Radiology Jun 2024Differentiating intracranial aneurysms from normal variants using CT angiography (CTA) or MR angiography (MRA) poses significant challenges. This study aimed to evaluate... (Comparative Study)
Comparative Study
Diagnosis of Unruptured Intracranial Aneurysms Using Proton-Density Magnetic Resonance Angiography: A Comparison With High-Resolution Time-of-Flight Magnetic Resonance Angiography.
OBJECTIVE
Differentiating intracranial aneurysms from normal variants using CT angiography (CTA) or MR angiography (MRA) poses significant challenges. This study aimed to evaluate the efficacy of proton-density MRA (PD-MRA) compared to high-resolution time-of-flight MRA (HR-MRA) in diagnosing aneurysms among patients with indeterminate findings on conventional CTA or MRA.
MATERIALS AND METHODS
In this retrospective analysis, we included patients who underwent both PD-MRA and HR-MRA from August 2020 to July 2022 to assess lesions deemed indeterminate on prior conventional CTA or MRA examinations. Three experienced neuroradiologists independently reviewed the lesions using HR-MRA and PD-MRA with reconstructed voxel sizes of 0.25 mm or 0.2 mm, respectively. A neurointerventionist established the gold standard with digital subtraction angiography. We compared the performance of HR-MRA, PD-MRA (0.25-mm voxel), and PD-MRA (0.2-mm voxel) in diagnosing aneurysms, both per lesion and per patient. The Fleiss kappa statistic was used to calculate inter-reader agreement.
RESULTS
The study involved 109 patients (average age 57.4 ± 11.0 years; male:female ratio, 11:98) with 141 indeterminate lesions. Of these, 78 lesions (55.3%) in 69 patients were confirmed as aneurysms by the reference standard. PD-MRA (0.25-mm voxel) exhibited significantly higher per-lesion diagnostic performance compared to HR-MRA across all three readers: sensitivity ranged from 87.2%-91.0% versus 66.7%-70.5%; specificity from 93.7%-96.8% versus 58.7%-68.3%; and accuracy from 90.8%-92.9% versus 63.8%-69.5% ( ≤ 0.003). Furthermore, PD-MRA (0.25-mm voxel) demonstrated significantly superior per-patient specificity and accuracy compared to HR-MRA across all evaluators ( ≤ 0.013). The diagnostic accuracy of PD-MRA (0.2-mm voxel) surpassed that of HR-MRA and was comparable to PD-MRA (0.25-mm voxel). The kappa values for inter-reader agreements were significantly higher in PD-MRA (0.820-0.938) than in HR-MRA (0.447-0.510).
CONCLUSION
PD-MRA outperformed HR-MRA in diagnostic accuracy and demonstrated almost perfect inter-reader consistency in identifying intracranial aneurysms among patients with lesions initially indeterminate on CTA or MRA.
Topics: Humans; Intracranial Aneurysm; Male; Female; Middle Aged; Magnetic Resonance Angiography; Retrospective Studies; Aged; Adult; Sensitivity and Specificity; Angiography, Digital Subtraction; Computed Tomography Angiography; Cerebral Angiography
PubMed: 38807339
DOI: 10.3348/kjr.2023.1241 -
CPT: Pharmacometrics & Systems... May 2024A physiologically-based pharmacokinetic (PBPK) model for tipifarnib, which included mechanistic absorption, was built and verified by integrating in vitro data and...
A physiologically-based pharmacokinetic (PBPK) model for tipifarnib, which included mechanistic absorption, was built and verified by integrating in vitro data and several clinical data in healthy subjects and cancer patients. The final PBPK model was able to recover the clinically observed single and multiple-dose plasma concentrations of tipifarnib in healthy subjects and cancer patients under several dosing conditions, such as co-administration with a strong CYP3A4 inhibitor and inducer, an acid-reducing agent (proton pump inhibitor and H2 receptor antagonist), and with a high-fat meal. In addition, the model was able to accurately predict the effect of mild or moderate hepatic impairment on tipifarnib exposure. The appropriately verified model was applied to prospectively simulate the liability of tipifarnib as a victim of CYP3A4 enzyme-based drug-drug interactions (DDIs) with a moderate inhibitor and inducer as well as tipifarnib as a perpetrator of DDIs with sensitive substrates of CYP3A4, CYP2B6, CYP2D6, CYP2C9, and CYP2C19 in healthy subjects and cancer patients. The effect of a high-fat meal, acid-reducing agent, and formulation change at the therapeutic dose was simulated. Finally, the model was used to predict the effect of mild, moderate, or severe hepatic, and renal impairment on tipifarnib PK. This multipronged approach of combining the available clinical data with PBPK modeling-guided dosing recommendations for tipifarnib under several conditions. This example showcases the totality of the data approach to gain a more thorough understanding of clinical pharmacology and biopharmaceutic properties of oncology drugs in development.
PubMed: 38807307
DOI: 10.1002/psp4.13165