Introduction

Helicobacter pylori eradication with standard triple therapy fails in ≥20% of the cases, mainly due to bacterial antibiotic resistances. Non-bismuth quadruple concomitant therapy is among the most widely used first-line treatments against H. pylori infection, even in high clarithromycin resistance areas.

Aims & Methods

To evaluate the efficacy and safety of non-bismuth quadruple concomitant therapy (proton pump inhibitor, clarithromycin, amoxicillin and nitroimidazole) in the treatment of H. pylori infection, and to compare it with other triple and quadruple regimens.
Bibliographical searches were performed in PubMed up to April 2024. We performed a meta-analysis of the studies evaluating the concomitant therapy as a first-line regimen, and of the randomised controlled trials comparing concomitant vs. standard triple, sequential, hybrid, and bismuth quadruple therapies.

Results

115 studies (78 randomised trials) were included (23,454 patients); 39 studies compared concomitant vs triple (13,494 patients), 38 studies vs sequential (11,907 patients), 12 studies vs hybrid (3,719 patients) and 11 studies vs bismuth quadruple (3,258 patients). Concomitant regimen achieved an overall eradication rate of 86% (95%CI=85-86%) by intention-to-treat, and 90% (90-91%) by per-protocol. Concomitant therapy achieved high eradication rates even in single clarithromycin resistant (89%) and metronidazole resistant (95%) patients, but poor cure rates in dual (clarithromycin and metronidazole) resistance (68%). The overall efficacy by intention-to-treat with concomitant therapy was significantly higher as compared to both triple therapy (risk difference [RD]=0.11; 95%CI=0.09-0.14; 39 studies) and sequential therapy (RD=0.04; 0.02-0.06; 38 studies); however, in the latter comparison, when only 14-day prescriptions were considered, no significant differences were observed (RD=0.01; -0.05-0.06; 4 studies). Likewise, the overall efficacy of concomitant therapy was similar to hybrid (RD=0.01; -0.01-0.03; 12 studies), and to bismuth quadruple therapy (encompassing the classical form and the single-capsule (RD=0.01; -0.03, 0.06; 11 studies). The overall incidence of adverse events with concomitant therapy was 37% (36-38%) (85 studies). When comparing only the studies with the same treatment durations, the incidence of adverse events with concomitant therapy was similar to that of triple (RD=0.04; -0.01-0.09; 15 studies), sequential (RD=0.03; -0.00-0.06; 16 studies), and bismuth quadruple therapies (RD=0.02; -0.06-0.09; 7 studies), but higher than that of hybrid therapies (RD=0.10; 0.04-0.15; 7 studies).

Conclusion

Non-bismuth quadruple concomitant therapy is highly effective for H. pylori eradication (achieving a cure rate of approximately 90%), even in the presence of clarithromycin or metronidazole resistance, being superior to standard triple and sequential therapies, and similar to hybrid and bismuth quadruple regimens. The incidence of adverse events with concomitant treatment is relatively high (37%), similar to that of triple and bismuth quadruple regimens.

Disclosure

Javier P. Gisbert has served as speaker, consultant, and advisory member for or has received research funding from: Mayoly, Allergan/Abbvie, Diasorin, Richen, Juvisé and Biocodex.
Olga P. Nyssen received research funding from: Mayoly, Allergan/Abbvie, Richen, Juvisé and Biocodex.

Introduction

Critically ill patients are at high risk for upper gastrointestinal (GI) bleeding.¹ Proton pump inhibitors (PPIs) are commonly used for prophylaxis, but their safety and efficacy compared to histamine-2 receptor antagonists (H2 blockers) and placebo remain unclear.^1–4

Aims & Methods

Our systematic review and meta-analysis aims to assess the safety and efficacy of PPIs for preventing upper GI bleeding in critically ill adults. We conducted a comprehensive search of Scopus, Web of Science, PubMed, and Cochrane Central for relevant randomized controlled trials (RCTs) from inception until March 2024. Data were extracted from eligible studies and pooled as mean difference (MD) for continuous outcomes and Odds ratio (OR) for dichotomous data in a random-effect model meta-analysis, using R software.

Results

Nineteen RCTs were included in this meta-analysis with a total of 62221 patients. Our study showed that PPI was superior to control in terms of GI bleeding [RR 0.55, (95% CI, 0.42 to 0.72); P = <0.01]. However, the overall effect did not favor either of the two groups in terms of ICU, mortality rate, and nosocomial infection [MD -1.45, (95% CI, -5.31 to 2.42); P = 0.4], [RR 1.04, (95% CI, 1.00 to 1.09); P = 0.07], and [RR 1.27, (95% CI, 0.98 to 1.65); P = 0.07], respectively.

Conclusion

In conclusion, our findings demonstrated a significant reduction in GI bleeding risk associated with PPI use. At the same time, we did not find a statistically significant difference between PPI and control groups regarding ICU mortality rate, overall mortality rate, or nosocomial infection rates. These findings suggest that PPIs may be effective in reducing upper GI bleeding in critically ill patients. However, further research might be necessary to definitively determine the impact of PPIs on mortality and infection risks in this population.

References

.1. Wang Y, Ye Z, Ge L, et al. Efficacy and safety of gastrointestinal bleeding prophylaxis in critically ill patients: Systematic review and network meta-analysis. The BMJ. 2020;368. doi:10.1136/bmj.l6744
2. Kondo Y, Ohbe H, Matsui H, Fushimi K, Tanaka H, Yasunaga H. Proton pump inhibitors versus histamine-2 receptor antagonists for stress ulcer prophylaxis during extracorporeal membrane oxygenation: a propensity score-matched analysis. BMJ Open. 2020;10(9):e037534. doi:10.1136/bmjopen-2020-037534
3. Alshamsi F, Belley-Cote E, Cook D, et al. Efficacy and safety of proton pump inhibitors for stress ulcer prophylaxis in critically ill patients: A systematic review and meta-analysis of randomized trials. Crit Care. 2016;20(1). doi:10.1186/S13054-016-1305-6
4. Jung YS, Park JH, Park CH. Impact of proton pump inhibitors on the risk of small bowel or colorectal bleeding: A systematic review and meta-analysis. United European Gastroenterol J. 2023;11(9):861-873. doi:10.1002/ueg2.12448

Introduction

Standard-of-care treatments for gastroesophageal reflux disease (GERD) include proton pump inhibitor (PPI)-based medical management and conventional antireflux surgery (i.e., Nissen fundoplication). However, these modalities are associated with a significant burden of unmet needs, such as irresponsiveness and postoperative adverse events (AEs), respectively. This study presents the results of 158 patients managed with RefluxStop in Germany.

Aims & Methods

One-hundred fifty-eight reflux patients were treated with RefluxStop between July 2021 and November 2023. Clinical endpoints included GERD Health-Related Quality of Life (GERD-HRQL), postoperative AEs, and change in PPI use.

Results

Baseline characteristics are shown in Table 1. Median GERD-HRQL score improved by 90.9% from a baseline of 22 (IQR 19-31.5) to 2 (IQR 0-2) at 20±7-month follow-up (p<.001). A 96.3% reduction in PPI use was also observed; baseline PPI use in 96.5% of n=113 decreased to 3.6% of n=110 at follow-up. All cases of preoperative dysphagia (n=18) resolved after surgery. New-onset dysphagia occurred in five patients (3.2%) postoperatively but did not require esophageal dilation. Hiatal hernia recurred in 1.3% (n=2) of patients and was managed with device repositioning. Device penetration and migration occurred in 1.3% (n=2) of patients due to excessively tight suturing of the fundic pouch in which the device was invaginated. One of these patients was later treated by Toupet fundoplication.

Table 1 Baseline characteristics

Conclusion

This report demonstrates the promising clinical effectiveness of RefluxStop as a novel treatment principle in management of GERD. Additional evaluation is necessary to enhance the evidence supporting this new antireflux procedure.

Disclosure

The authors disclose travel grants and speaking honoraria from Implantica (Zug, Switzerland).

Clinical Case Summary

Introduction: Gastric siderosis (GS) refers to the abnormal deposition of iron within the gastric mucosa, a condition that can be associated with various underlying pathologies. Our case depicts a case of gastric siderosis with iron deposition in the stomach in association with excessive oral iron intake, presenting unusually with chronic diarrhea. Such association has been mentioned previously in the literature but not established.
Case: A 70-year-old lady with a history of iron deficiency anemia and chronic kidney disease presented with 3 weeks of progressively worsening diarrhea. Home medicines included iron pills. She denied any blood in stool, abdominal pain, recent travel, or antibiotic use. Her vitals and her abdominal exam were unremarkable. Stool studies, including stool parasite, C. difficile toxin, calprotectin, and bacterial PCR, were negative.
Colonoscopy showed a normal macroscopic appearance with random biopsies negative for microscopic colitis. An upper endoscopy was performed demonstrating normal esophagus but pitted brown spots mucosa in the gastric body, and antrum. Biopsies were taken, with antral ones demonstrating antral mucosa with iron deposition in the glands and lamina propria concerning gastric siderosis. Oral iron was discontinued and the patient endorsed improvement in symptoms upon outpatient follow-up with endoscopic resolution at 6 months.
Discussion: Iron deposition in gastric mucosa induces a highly oxidative state, producing injury. However, siderosis due to oral iron use is less commonly associated with mucosal injury, with cases seen with changes ranging from erythema to mucosal erosions. Our patient had pattern B on biopsy involving stroma, whereas A involves macrophages in gastric inflammation, and C involves glands in hemochromatosis. No association with the duration or amount of exposure is associated with differences in symptoms. Non-bloody diarrhea occurs without active ulceration being reported, making our patient unique.

References

1. Marginean EC, Bennick M, et al. Gastric siderosis: patterns and significance. Am J Surg Pathol. 2006 Apr;30(4):514-20. doi: 10.1097/00000478-200604000-00013. PMID: 16625099.
2. Abraham SC, Yardley JH, Wu TT. Erosive injury to the upper gastrointestinal tract in patients receiving iron medication: an underrecognized entity. Am J Surg Pathol. 1999 Oct;23(10):1241-7. doi: 10.1097/00000478-199910000-00009. PMID: 10524525.
3. Siah CW, Ombiga et al. Normal iron metabolism and the pathophysiology of iron overload disorders. Clin Biochem Rev. 2006 Feb;27(1):5-16. PMID: 16886043; PMCID: PMC1390789.
4. Idoate Gastearena MA, et al. A comparative study on the gastroduodenal tolerance of different antianaemic preparations. Hum Exp Toxicol. 2003 Mar;22(3):137-41. doi: 10.1191/0960327103ht330oa. PMID: 12723894.
5. Wang J, Pantopoulos K. Regulation of cellular iron metabolism. Biochem J. 2011 Mar 15;434(3):365-81. doi: 10.1042/BJ20101825. PMID: 21348856; PMCID: PMC3048577.
6. Hattori H. High prevalence of haemosiderin accumulation in the cytoplasm of gastric glands in patients with liver cirrhosis. J Clin Pathol. 2004 Jun;57(6):621-4. doi: 10.1136/jcp.2003.010405. PMID: 15166268; PMCID: PMC1770335.
7. De Petris G, Gatius Caldero S, et al. Histopathological changes in the gastrointestinal tract due to drugs: an update for the surgical pathologist (part I of II). Int J Surg Pathol. 2014 Apr;22(2):120-8. doi: 10.1177/1066896913502229. Epub 2013 Sep 10. PMID: 24021899.

Clinical Case Summary

We present the case of a 50-year-old man with six months of persistent, non-bloody watery diarrhea (8–10 episodes/day), unresponsive to antibiotics and probiotics. His past medical history was unremarkable, he took no home medications, and denied raw meat or fish consumption. Notably, he had recently started working in an animal feed production facility one month before symptom onset. Initial labs showed mild leukocytosis (10.04 x 10³/µL; ULN: 8.77) and mildly elevated CRP (7.5 mg/L; ULN: 3.4). Extensive infectious workup, including CMV serology, Quantiferon, stool cultures for Salmonella, and tests for fungi and parasites (e.g., Giardia), fecal elastase, rectal swabs for Klebsiella pneumoniae carbapenemase and Clostridium difficile returned negative. Colonoscopy and upper GI endoscopy were normal, and biopsies from all intestinal segments showed no pathological findings. He was discharged with partial improvement (3–4 bowel movements/day) and normalized CRP, but was readmitted a week later for worsening symptoms. Repeat blood work, thyroid function, serum calcitonin and inflammatory markers were within normal limits. Intestinal ultrasound showed a tubular descending colon suggestive of nonspecific left-sided colitis; other bowel segments were normal. Stool tests remained negative.Urine toxicology was positive for cannabinoids. Upon further questioning, the patient admitted to regular use over the past eight months, including during both hospitalisations (CUDIT-R score = 12). After cessation of cannabinoid use, diarrhea resolved completely. At 3-month follow-up, he was asymptomatic, with normal bowel habits and labs. He reported only sporadic cannabinoid use at present (CUDIT-R score 7). This case illustrates the potential for chronic cannabinoid use to induce persistent diarrhea mimicking infectious or inflammatory disease. Screening for substance use should be considered in chronic unexplained diarrhea.

Introduction

Ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasonography (EUS), and fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) are widely used to evaluate gallbladder disease.
However, there are some cases difficult to diagnose even with those modalities. In recent years, the image quality of diffusion-weighted imaging (DWI) has improved with the development of MRI systems. The usefulness of DWI for gallbladder disease has been reported in several studies. PET has some limitations, such as high cost, radiation exposure, and influence by blood glucose levels. The purpose of this study was to compare the usefulness of DWI with PET in the diagnosis of gallbladder disease.

Aims & Methods

Forty-two patients who underwent preoperative DWI and PET for gallbladder disease were included. The final diagnosis was made histologically on excised specimens. Of the 42 patients, 24 had malignant conditions (23 had gallbladder cancer, and 1 had neuroendocrine cancer), and 18 had benign conditions (9 had chronic cholecystitis, 3 had adenomyomatosis, 4 had polyps, 1 had gallbladder adenoma, and 1 had xanthogranulomatous cholecystitis). We evaluated the accuracy of DWI and the apparent diffusion coefficient (ADC) value of each disease.

Results

The sensitivity of DWI and PET was 88% vs 88% (p = 1.0), the specificity was 61% vs 56% (p = 0.56), and the accuracy was 76% vs 74% (p = 0.56), showing no significant difference. The mean ADC value of malignant diseases was (1.71±0.29) × 10-3mm2/s, and that of benign diseases was (2.33±0.36) × 10-3mm2/s (p < 0.001). The mean ADC value of malignant diseases was significantly lower than that of benign diseases.

Conclusion

In this study, DWI had a similar accuracy compared to PET. DWI compensates for the limitations of PET and can be performed in a more noninvasive manner. The combined use of DWI and ADC was suggested to contribute to the improvement of the diagnostic capability for gallbladder diseases.

References

​