-
Enzyme and Microbial Technology Jun 2024Esomeprazole is the most popular proton pump inhibitor for treating gastroesophageal reflux disease. Previously, a phenylacetone monooxygenase mutant LnPAMOmu15 (LM15)...
Esomeprazole is the most popular proton pump inhibitor for treating gastroesophageal reflux disease. Previously, a phenylacetone monooxygenase mutant LnPAMOmu15 (LM15) was obtained by protein engineering for asymmetric synthesis of esomeprazole using pyrmetazole as substrate. To scale up the whole cell asymmetric synthesis of esomeprazole and reduce the cost, in this work, an Escherichia coli whole-cell catalyst harboring LM15 and formate dehydrogenase from Burkholderia stabilis 15516 (BstFDH) were constructed through optimized gene assembly patterns. CRISPR/Cas9 mediated insertion of P promoter in genome was done to enhance the expression of key genes to increase the cellular NADP supply in the whole cell catalyst, by which the amount of externally added NADP for the asymmetric synthesis of esomeprazole decreased to 0.05 mM from 0.3 mM for reducing the cost. After the optimization of reaction conditions in the reactor, the scalable synthesis of esomeprazole was performed using the efficient LM15-BstFDH whole-cell as catalyst, which showed the highest reported space-time yield of 3.28 g/L/h with 50 mM of pyrmetazole loading. Isolation procedure was conducted to obtain esomeprazole sodium of 99.55 % purity and > 99.9 % ee with 90.1 % isolation yield. This work provides the basis for production of enantio-pure esomeprazole via cost-effective whole cell biocatalysis.
PubMed: 38878426
DOI: 10.1016/j.enzmictec.2024.110469 -
Medicine Jun 2024Approximately 10% to 40% of patients with gastroesophageal reflux disease (GERD) exhibit poor response to proton pump inhibitors (PPIs), indicating refractory GERD... (Randomized Controlled Trial)
Randomized Controlled Trial
Approximately 10% to 40% of patients with gastroesophageal reflux disease (GERD) exhibit poor response to proton pump inhibitors (PPIs), indicating refractory GERD (RGERD). Banxia Houpu Decoction is a traditional Chinese medicine formula used for treating GERD, particularly for atypical symptoms. This study aimed to investigate the improvement of different symptoms in RGERD patients treated with Banxia Houpu Decoction and identify relevant factors influencing its efficacy. From November 2021 to November 2022, a total of 89 RGERD patients voluntarily participated in this clinical study at our hospital. They were randomly assigned to 2 treatment groups: the Banxia Houpu Decoction group and the Western medicine group. The former received standard-dose Banxia Houpu Decoction, while the latter had a switch in PPI type with double-dose maintenance and the addition of magnesium aluminum carbonate as an acid suppressant. The improvement of different symptoms was compared between the 2 groups. Clinical data, including age, gender, gastric mucosal status, and esophagitis severity, were collected. Univariate analysis was performed to explore factors influencing the therapeutic effect of Banxia Houpu Decoction. Both treatment groups showed significant improvement in Frequency Scale for the Symptoms of GERD (FSSG) scores. The Banxia Houpu Decoction group exhibited the most significant efficacy in relieving throat burning sensation (P = .003) and frequent hiccups (P = .003). It also demonstrated improvement in swallowing difficulty (P = .048) and postprandial abdominal distension (P = .041), surpassing the Western medicine group. The Western medicine group had the most significant improvement in heartburn sensation (P = .008) and showed significant improvement in gastric burning sensation (P = .022), surpassing Banxia Houpu Decoction. Age (P = .025) and gastroesophageal flap valve (GEFV) grade (P = .014) were identified as factors influencing the efficacy of Banxia Houpu Decoction. Banxia Houpu Decoction exhibits superior efficacy compared to double-dose PPI combined with acid suppressants in relieving symptoms such as throat burning sensation, swallowing difficulty, and frequent hiccups. It shows significant efficacy in patients under 60 years of age and with GEFV grades I-II.
Topics: Humans; Gastroesophageal Reflux; Male; Female; Middle Aged; Drugs, Chinese Herbal; Proton Pump Inhibitors; Adult; Treatment Outcome; Aged
PubMed: 38875370
DOI: 10.1097/MD.0000000000038045 -
Molecular Biology Reports Jun 2024Gastrointestinal cancer is the most fatal cancer worldwide. The etiology of gastrointestinal cancer has yet to be fully characterized. Alcohol consumption, obesity,... (Review)
Review
Gastrointestinal cancer is the most fatal cancer worldwide. The etiology of gastrointestinal cancer has yet to be fully characterized. Alcohol consumption, obesity, tobacco, Helicobacter pylori and gastrointestinal disorders, including gastroesophageal reflux disease, gastric ulcer, colon polyps and non-alcoholic fatty liver disease are among the several risks factors for gastrointestinal cancers. Phycocyanin which is abundant in Spirulina. Phycocyanin, a member of phycobiliprotein family with intense blue color, is an anti-diabetic, neuroprotective, anti-oxidative, anti-inflammatory, and anticancer compound. Evidence exists supporting that phycocyanin has antitumor effects, exerting its pharmacological effects by targeting a variety of cellular and molecular processes, i.e., apoptosis, cell-cycle arrest, migration and Wnt/β-catenin signaling. Phycocyanin has also been applied in treatment of several gastrointestinal disorders such as, gastric ulcer, ulcerative colitis and fatty liver that is known as a risk factor for progression to cancer. Herein, we summarize various cellular and molecular pathways that are affected by phycocyanin, its efficacy upon combined drug treatment, and the potential for nanotechnology in its gastrointestinal cancer therapy.
Topics: Humans; Phycocyanin; Gastrointestinal Neoplasms; Antineoplastic Agents; Animals; Apoptosis; Gastrointestinal Diseases
PubMed: 38874869
DOI: 10.1007/s11033-024-09675-3 -
Surgery For Obesity and Related... May 2024Insufficient weight loss after primary laparoscopic sleeve gastrectomy (LSG) occasionally requires revisional surgery. A few single-institution studies have examined the...
BACKGROUND
Insufficient weight loss after primary laparoscopic sleeve gastrectomy (LSG) occasionally requires revisional surgery. A few single-institution studies have examined the safety of redo LSG (RSG) and have shown mixed results.
OBJECTIVES
The aim of this study was to evaluate the safety of RSG compared with LSG over a period of 30 days.
SETTING
University of Southern California, United States; Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database.
METHODS
The 2020-2021 MBSAQIP registry was used to evaluate patients who underwent RSG. Thirty-day outcomes were evaluated using univariable analysis and multivariable logistic and linear regression.
RESULTS
A total of 226,029 patients were reviewed, of whom 1454 (.7%) underwent RSG and 224,575 (99.3%) underwent initial LSG. Patients who underwent RSG were older (45 versus 42 yr), predominantly female (86.2% versus 81.3%), had a lower body mass index (40.0 versus 43.4), fewer co-morbidities, and greater rates of gastroesophageal reflux (38.7% versus 25.1%). They demonstrated increased overall complications (3.6% versus 2.1%, P < .001) and a longer operative time (81 versus 62 min, P < .001), but there was no difference in mortality. On multivariable analysis, patients who underwent RSG were independently associated with an increased risk of overall postoperative complications (odds ratio [OR]: 1.493, P = .018), organ space infection (OR: 6.231, P < .001), staple line leak (OR: 12.838, P < .001), pneumonia (OR: 3.85, P = .013), ventilator requirement over 48 hours (OR: 6.404, P = .035), sepsis (OR: 4.397, P = .010), septic shock (OR: 8.669, P < .001), reoperation (OR: 1.808, P = .013), readmission (OR: 2.104, P < .001), reintervention (OR: 4.435, P < .001), and longer operative times (β = 12.790, P < .001).
CONCLUSIONS
In this national database study, RSG was associated with increased rates of postoperative complications and a longer operative time. Although these results are concerning, further studies are required to examine long-term outcomes.
PubMed: 38871494
DOI: 10.1016/j.soard.2024.04.016 -
International Journal of Surgery... Jun 2024Cholecystectomy is the standard surgery for patients with gallbladder disease, but the impact of cholecystectomy on gastroesophageal reflux disease (GERD) is not clear.
BACKGROUND
Cholecystectomy is the standard surgery for patients with gallbladder disease, but the impact of cholecystectomy on gastroesophageal reflux disease (GERD) is not clear.
METHODS
We obtained genetic variants associated with cholecystectomy at a genome-wide significant level (P value<5 × 10-8) as instrumental variables (IVs) and performed Mendelian randomization (MR) to explore the relationship with GERD.
RESULTS
The Inverse Variance Weighted analysis (IVW) showed that the risk of GERD in patients after cholecystectomy increased (OR=2.19; 95% CI: 1.18 - 4.09). At the same time, the analysis results of weighted median (OR=2.30; 95% CI: 1.51 - 3.48) and weighted mode (OR=2.21; 95% CI: 1.42 - 3.45) were also consistent with the direction of the IVW analysis and were statistically significant (P<0.05).
CONCLUSIONS
This study shows that patients who have undergone cholecystectomy are a susceptible population of GERD.
PubMed: 38869973
DOI: 10.1097/JS9.0000000000001806 -
Journal of Clinical Gastroenterology Jun 2024As a GABAB receptor agonist, baclofen has demonstrated efficacy in alleviating symptoms of refractory gastroesophageal reflux disease (r-GERD). This meta-analysis aims...
OBJECTIVES
As a GABAB receptor agonist, baclofen has demonstrated efficacy in alleviating symptoms of refractory gastroesophageal reflux disease (r-GERD). This meta-analysis aims to evaluate the safety and effectiveness of baclofen as an add-on therapy for this condition.
METHOD
We conducted a comprehensive search of the PubMed, Embase, and Web of Science databases for studies published up until October 2023. Subsequently, we performed a meta-analysis encompassing all eligible trials.
RESULTS
From 719 records, 10 studies were included, most of these studies were moderate risk. The findings demonstrated that the addition of baclofen as a supplementary treatment effectively improves symptoms (GERD Q score) in r-GERD (standardized mean difference=-0.78, 95% CI: -1.06 to -0.51, I2=0%). The addition of this treatment also resulted in a decrease in the frequency of nonacidic reflux episodes (standardized mean difference=-0.93, 95% CI: -1.49 to -0.37, I2=63%) and an improvement in DeMeester scores (standardized mean difference=-0.82, 95% CI: -1.61 to -0.04, I2=81%) among patients with r-GERD when compared with the use of proton pump inhibitor (PPI) drugs alone. However, no significant disparity was observed in terms of reducing acid reflux episodes (standardized mean difference=-0.12, 95% CI: -0.49 to 0.19, I2=0%) and proximal reflux (standardized mean difference=-0.47, 95% CI: -1.08 to 0.14, I2=60%).
CONCLUSION
Baclofen as an add-on treatment can effectively improve the symptoms of patients with r-GERD and reduce the incidence of nonacidic reflux and improve DeMeester score. However, long-term use of baclofen leads to an increased incidence of side effects and is not effective in reducing the occurrence of acid reflux.
PubMed: 38869961
DOI: 10.1097/MCG.0000000000002021 -
Expert Review of Gastroenterology &... Jun 2024Although gastrointestinal (GI) comorbidities are experienced by over 90% of individuals with Rett syndrome (RTT), a neurodevelopmental disorder associated with mutations...
INTRODUCTION
Although gastrointestinal (GI) comorbidities are experienced by over 90% of individuals with Rett syndrome (RTT), a neurodevelopmental disorder associated with mutations in the MECP2 gene, many neurologists and pediatricians do not rank the management of these comorbidities among the most important treatment goals for RTT. Trofinetide, the first approved pharmacologic treatment for RTT, confers improvements in RTT symptoms but is associated with adverse GI events, primarily diarrhea and vomiting. Treatment strategies for GI comorbidities and drug-associated symptoms in RTT represent an unmet clinical need.
AREAS COVERED
This perspective covers GI comorbidities experienced by those with RTT, either with or without trofinetide treatment. PubMed literature searches were undertaken on treatment recommendations for the following conditions: constipation, diarrhea, vomiting, aspiration, dysphagia, gastroesophageal reflux, nausea, gastroparesis, gastritis, and abdominal bloating.
EXPERT OPINION
The authors recommend a proactive approach to management of symptomatic GI comorbidities and drug-associated symptoms in RTT to enhance drug tolerance and improve the quality of life of affected individuals. Management strategies for common GI comorbidities associated with RTT are reviewed based on authors' clinical experience and augmented by recommendations from the literature.
PubMed: 38869952
DOI: 10.1080/17474124.2024.2368014 -
Zhongguo Zhen Jiu = Chinese Acupuncture... Jun 2024To observe the effect of acupuncture on gastroesophageal reflux disease (GERD) based on the "heart-stomach connection" theory, and to explore its possible mechanisms. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To observe the effect of acupuncture on gastroesophageal reflux disease (GERD) based on the "heart-stomach connection" theory, and to explore its possible mechanisms.
METHODS
Seventy patients with GERD were randomly divided into an acupuncture group (35 cases, 2 cases dropped out) and a medication group (35 cases, 1 case dropped out). The patients in the acupuncture group received acupuncture at bilateral Shenmen (HT 7), Neiguan (PC 6), Burong (ST 19), Tianshu (ST 25), Zusanli (ST 36), Gongsun (SP 4), and Zhongwan (CV 12), with needles retained for 30 min, every other day, three times a week. The patients in the medication group were treated with oral omeprazole capsules, once daily, 20 mg each time. Both groups were treated for 8 weeks. Before and after treatment, the GERD questionnaire (GERDQ), GERD-quality of life scale (GERD-QOL), Hamilton depression scale-24 (HAMD-24), Zung self-rating depression scale (SDS), and Zung self-rating anxiety scale (SAS) scores were observed. Serum levels of gastrointestinal hormones (gastrin [GAS], motilin [MTL], and vasoactive intestinal peptide [VIP]) were measured, and the clinical efficacy of both groups was evaluated. Correlation between pre-treatment GERDQ score and GERD-QOL score, HAMD-24 score, SDS score, and SAS score was analyzed.
RESULTS
After treatment, the scores of GERDQ, HAMD-24, SDS, and SAS were decreased (<0.001) and the scores of GERD-QOL were increased (<0.001), serum levels of GAS and MTL were increased (<0.001) in both groups, while the serum level of VIP in the acupuncture group was decreased (<0.001) compared with those before treatment. The acupuncture group had higher GERD-QOL score and lower SAS score than the medication group (<0.05), with lower serum VIP level (<0.05). The total effective rate was 75.8% (25/33) in the acupuncture group, and 76.5% (26/34) in the medication group, with no significant difference between the two groups (>0.05). GERDQ score was negatively correlated with GERD-QOL scores ( =-0.762, <0.01) and positively correlated with HAMD-24 score, SDS score, and SAS score ( =0.709, 0.649, 0.689, <0.01) before treatment.
CONCLUSION
Based on the "heart-stomach connection" theory, acupuncture could effectively improve clinical symptoms, quality of life, and negative emotions in patients with GERD. Its mechanism may be related to the regulation of gastrointestinal hormone levels, thereby promoting the contraction of the lower esophageal sphincter.
Topics: Humans; Gastroesophageal Reflux; Acupuncture Therapy; Male; Female; Middle Aged; Adult; Aged; Gastrointestinal Hormones; Acupuncture Points; Young Adult; Stomach; Heart; Motilin
PubMed: 38867622
DOI: 10.13703/j.0255-2930.20230818-0004 -
Obesity Surgery Jun 2024The incidence of unresolved postoperative reflux after bariatric surgery varies considerably. Consistent perioperative patient characteristics predictive of unresolved...
PURPOSE
The incidence of unresolved postoperative reflux after bariatric surgery varies considerably. Consistent perioperative patient characteristics predictive of unresolved reflux remain unknown. We leverage our institution's comprehensive preoperative esophageal testing to identify predictors of postoperative reflux.
MATERIALS AND METHODS
We performed a single-center retrospective review of adult patients with preoperative reflux symptoms who underwent either vertical sleeve gastrectomy (VSG) or Roux-en-Y gastric bypass (RYGB) from 2015 to 2021. All patients had pH and high-resolution manometry preoperatively. Predictors of postoperative unresolved reflux at 1 year were explored via Fisher's exact test, Kruskal Wallis test, and univariate logistic regression.
RESULTS
Unresolved reflux was higher in patients undergoing VSG (n = 60/129,46.5%) vs. RYGB (n = 19/98, 19.4%). Median DeMeester scores were higher (22 vs. 13, p = .07) along with rates of ineffective esophageal motility (IEM) (31.6 vs. 8.9%, p = .01) in the 19 (19.3%) patients with unresolved postoperative reflux after RYGB compared to the resolved RYGB reflux cohort. Sixty (46.5%) of VSG patients had unresolved postoperative reflux. The VSG unresolved reflux cohort had similar median DeMeester and IEM incidence to the resolved VSG group but more preoperative dysphagia (13.3% vs. 2.9%, p = .04) and higher preoperative PPI use (56.7 vs. 39.1%, p = .05). In univariate analysis, only IEM was predictive of unresolved reflux after RYGB (OR 4.74, 95% CI 1.37, 16.4).
CONCLUSION
Unresolved reflux was higher after VSG. Preoperative IEM predicted unresolved reflux symptoms after RYGB. In VSG patients, preoperative dysphagia symptoms and PPI use predicted unresolved reflux though lack of correlation to objective testing highlights the subjective nature of symptoms and the challenges in predicting postoperative symptomatology.
PubMed: 38867101
DOI: 10.1007/s11695-024-07311-4 -
Surgical Endoscopy Jun 2024Treatment options for gastroesophageal reflux disease (GERD) that is unresponsive to proton pump inhibitors (PPIs) remain limited. Therefore, we compared the therapeutic...
Comparative evaluation of endoscopic anti-reflux mucosectomy and stretta radiofrequency ablation in the management of gastroesophageal reflux disease: insights from a retrospective multicenter cohort study.
BACKGROUND
Treatment options for gastroesophageal reflux disease (GERD) that is unresponsive to proton pump inhibitors (PPIs) remain limited. Therefore, we compared the therapeutic effects of anti-reflux mucosectomy (ARMS) and Stretta radiofrequency (SRF) for intractable GERD in over 400 individuals who underwent either procedure.
METHODS
We conducted a retrospective study between 2016 and 2023 to evaluate the effectiveness of SRF and ARMS treatments for refractory GERD. The primary measure of success was the change in the GERD questionnaire (GERDQ) score. The secondary outcomes were various GERD-related indicators, including endoscopic Los Angeles (LA) classification, Hill's type-based flap valve grade (FVG), EndoFLIP™ distensibility index (DI), rate of PPI discontinuation, resolution rate of Barrett's esophagus, and incidence of adverse events.
RESULTS
The ARMS group included patients with high GERDQ scores, FVG, LA grade, and Barrett's esophagus. Both groups had similar rates of improvements in GERDQ score (P = 0.884) and PPI withdrawal (P = 0.866); however, the ARMS group had significantly more side effects and improvements in the median change in GERDQ score (P = 0.011), FVG (P < 0.001), LA grade (P < 0.001), EndoFLIP™ DI (P < 0.001), and resolution of Barrett's esophagus (P < 0.001).
CONCLUSIONS
The ARMS group had a greater GERDQ score improvement than the SRF group but had symptom relief and PPI discontinuation rates similar to those of the SRF group. However, objective measures, including EndoFLIP™ DI and endoscopic evaluations, were better in the ARMS group than in the SRF group.
PubMed: 38866947
DOI: 10.1007/s00464-024-10947-z