Vonoprazan-amoxicillin dual regimen with Saccharomyces boulardii as a rescue therapy for Helicobacter pylori:Current perspectives and implications

Yu et al’s study in the World Journal of Gastroenterology(2023)introduced a novel regimen of Vonoprazan-amoxicillin dual therapy combined with Saccharomyces boulardii(S.boulardii)for the rescue therapy against Helicobacter pylori(H.pylori),a pathogen responsible for peptic ulcers and gastric cancer.Vonoprazan is a potassium-competitive acid blocker renowned for its rapid and long-lasting acid suppression,which is minimally affected by mealtime.Compared to proton pump inhibitors,which bind irreversibly to cysteine residues in the H+/K+-ATPase pump,Vonoprazan competes with the K+ions,prevents the ions from binding to the pump and blocks acid secretion.Concerns with increasing antibiotic resistance,effects on the gut microbiota,patient compliance,and side effects have led to the advent of a dual regimen for H.pylori.Previous studies suggested that S.boulardii plays a role in stabilizing the gut barrier which improves H.pylori eradication rate.With an acceptable safety profile,the dual-adjunct regimen was effective regardless of prior treatment failure and antibiotic resistance profile,thereby strengthening the applicability in clinical settings.Nonetheless,S.boulardii comes in various formulations and dosages,warranting further exploration into the optimal dosage for supplementation in rescue therapy.Additionally,larger,randomized,double-blinded controlled trials are warranted to confirm these promising results.

Third-line and rescue therapy for refractory Helicobacter pylori infection: A systematic review

BACKGROUND Due to increasing resistance rates of Helicobacter pylori(H.pylori)to different antibiotics,failures in eradication therapies are becoming more frequent.Even though eradication criteria and treatment algorithms for first-line and second-line therapy against H.pylori infection are well-established,there is no clear recommendation for third-line and rescue therapy in refractory H.pylori infection.AIM To perform a systematic review evaluating the efficacy and safety of rescue therapies against refractory H.pylori infection.METHODS A systematic search of available rescue treatments for refractory H.pylori infection was conducted on the National Library of Medicine’s PubMed search platform based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Randomized or non-randomized clinical trials and observational studies evaluating the effectiveness of H.pylori infection rescue therapies were included.RESULTS Twenty-eight studies were included in the analysis of mean eradication rates as rescue therapy,and 21 of these were selected for analysis of mean eradication rate as third-line treatment.For rifabutin-,sitafloxacin-,levofloxacin-,or metronidazole-based triple-therapy as third-line treatment,mean eradication rates of 81.6%and 84.4%,79.4%and 81.5%,55.7%and 60.6%,and 62.0%and 63.0%were found in intention-to-treat(ITT)and per-protocol(PP)analysis,respectively.For third-line quadruple therapy,mean eradication rates of 69.2%and 72.1%were found for bismuth quadruple therapy(BQT),88.9%and 90.9%for bismuth quadruple therapy,three-in-one,Pylera®(BQT-Pylera),and 61.3%and 64.2%for non-BQT)in ITT and PP analysis,respectively.For rifabutin-,sitafloxacin-,levofloxacin-,or metronidazole-based triple therapy as rescue therapy,mean eradication rates of 75.4%and 78.8%,79.4 and 81.5%,55.7%and 60.6%,and 62.0%and 63.0%were found in ITT and PP analysis,respectively.For quadruple therapy as rescue treatment,mean eradication rates of 76.7%and 79.2%for BQT,84.9%and 87.8%for BQT-Pylera,and 61.3%and 64.2%for non-BQT were found in ITT and PP analysis,respectively.For susceptibility-guided therapy,mean eradication rates as third-line and rescue treatment were 75.0%in ITT and 79.2%in PP analysis.CONCLUSION We recommend sitafloxacin-based triple therapy containing vonoprazan in regions with low macrolide resistance profile.In regions with known resistance to macrolides or unavailability of bismuth,rifabutin-based triple therapy is recommended.

Safety and effectiveness of vonoprazan-based rescue therapy for Helicobacter pylori infection

BACKGROUND Vonoprazan(VPZ)-based regimens are an effective first-line therapy for Helicobacter pylori(H.pylori)infection.However,their value as a rescue therapy needs to be explored.AIM To assess a VPZ-based regimen as H.pylori rescue therapy.METHODS This prospective,single-center,clinical trial was conducted between January and August 2022.Patients with a history of H.pylori treatment failure were administered 20 mg VPZ twice daily,750 mg amoxicillin 3 times daily,and 250 mg Saccharomyces boulardii(S.boulardii)twice daily for 14 d(14-d VAS regimen).VPZ and S.boulardii were taken before meals,while amoxicillin was taken after meals.Within 3 d after the end of eradication therapy,all patients were asked to fill in a questionnaire to assess any adverse events they may have experienced.At least 4-6 wk after the end of eradication therapy,eradication success was assessed using a 13C-urea breath test,and factors associated with eradication success were explored.RESULTS Herein,103 patients were assessed,and 68 patients were finally included.All included patients had 1-3 previous eradication failures.The overall eradication rates calculated using intention-to-treat and per-protocol analyses were 92.6%(63/68)and 92.3%(60/65),respectively.The eradication rate did not differ with the number of treatment failures(P=0.433).The rates of clarithromycin,metronidazole,and levofloxacin resistance were 91.3%(21/23),100.0%(23/23),and 60.9%(14/23),respectively.There were no cases of resistance to tetracycline,amoxicillin,or furazolidone.In 60.9%(14/23)patients,the H.pylori isolate was resistant to all 3 antibiotics(clarithromycin,metronidazole,and levofloxacin);however,eradication was achieved in 92.9%(13/14)patients.All patients showed metronidazole resistance,and had an eradication rate of 91.3%(21/23).The eradication rate was higher among patients without anxiety(96.8%)than among patients with anxiety(60.0%,P=0.025).No severe adverse events occurred;most adverse events were mild and disappeared without intervention.Good compliance was seen in 95.6%(65/68)patients.Serological examination showed no significant changes in liver and kidney function.CONCLUSION VAS is a safe and effective rescue therapy,with an acceptable eradication rate(>90%),regardless of the number of prior treatment failures.Anxiety may be associated with eradication failure.

Third-line rescue therapy for Helicobacter pylori infection

H pylori gastric infection is one of the most prevalent infectious diseases worldwide. The discovery that most upper gastrointestinal diseases are related to Hpylori infection and therefore can be treated with antibiotics is an important medical advance. Currently, a first-line triple therapy based on proton pump inhibitor （PPI） or ranitidine bismuth citrate （RBC） plus two antibiotics （darithromycin and amoxicillin or nitroimidazole） is recommended by all consensus conferences and guidelines. Even with the correct use of this drug combination, infection can not be eradicated in up to 23% of patients. Therefore, several second line therapies have been recommended. A 7 d quadruple therapy based on PPI, bismuth, tetracycline and metronidazole is the more frequently accepted. However, with second-line therapy, bacterial eradication may fail in up to 40% of cases. When Hpylori eradication is striclly indicated the choice of further treatment is controversial. Currently, a standard third-line therapy is lacking and various protocols have been proposed. Even after two consecutive failures, the most recent literature data have demonsbated that Hpylori eradication can be achieved in almost all patients, even when antibiotic susceptibility is not tested. Different possibilities of empirical treatment exist and the available third-line strategies are herein reviewed.

Furazolidone,amoxicillin,bismuth and rabeprazole quadruple rescue therapy for the eradication of Helicobacter pylori

AIM： To compare the efficacy and side effect profiles of three furazolidone and amoxicillin-based quadruple rescue therapies for the eradication of Helicobacter pylori （H pylonS. METHODS： Patients who failed in the Hpylori eradication therapy for at least one course were randomly allocated into three groups. Group A received rebaprazole 10 mg＋ amoxicillin 1 g ＋ furazolidone 100 mg, and bismuth subcitrate 220 mg, twice daily for 1 wk; group B received the same regimen of group A but for 2 wk; and group C received the same regimen of group B, but furazolidone was replaced by furazolidone 100 mg three times daily. To record the side effect profiles at the end of the treatment, Hpylori eradication was assessed with 13C-urea breath test 4 wk after therapy. RESULTS： Sixty patients were enrolled including 28 males, and 20 patients in each group. The average age of the patients was 49.2 years, ranging from 18 to 84 years. H pylori eradication rates with per-protocol analysis were 82%, 89% and 90% in the three groups, respectively. Side effects were found in 11 patients, including mild dizziness, nausea, diarrhea and increased bowel movement. None of the 11 patients needed treatment for their side effects. CONCLUSION： One- or two-week furazolidone and amoxicillin-based quadruple rescue therapy with a low dose furazolidone （100 mg bid） for the eradication of Hpylori is effective. Extending the antibiotic course to 14 d could improve the eradication rates.

Helicobacter pylori:Future perspectives in therapy reflecting three decades of experience

The rising prevalence of antibiotic resistance has created a need to reassess the established Helicobacter pylori(H.pylori)eradication protocols,and to develop new ones.Various bacterial and host factors are evaluated,and their contribution to eradication failure is estimated.For a long time being considered the cornerstone eradication scheme,the standard triple therapy has been replaced with novel,more efficient regimens,namely sequential and concomitant,along with the emergence of a new design of bismuth quadruple therapy.A rescue levofloxacin based regimen has overcome the fear of therapy failure due to higher prevalence of dual resistant(clarithromycin and metronidazole)H.pylori.Culture-free and efficient susceptibility test are reestablishing the concept of tailored therapy,making eradication success close to originally desirable rates.Alleviating therapy side effects and improving patient compliance are as important as choosing appropriate eradication schemes,so various probiotic compound supplements are taken into consideration.Finally,we summarize the emerging efforts and obstacles in creating efficientH.pylori vaccine.

Furazolidone therapy for Helicobacter pylori:Is it effective and safe?

Some aspects related with the use of furazolidone as a rescue therapy for Helicobacter pylori （H pylorl） infection should be remarked, especially regarding its potential oncologic risk. The inclusion of furazolidone in a treatment regimen for H pylori infection is, at least, controversial, and it does not appear to be safe.

Rifabutin as salvage therapy for Helicobacter pylori eradication:Cornerstones and novelties

When several Helicobacter pylori eradication treatments fail,guidelines recommend a cultured guided approach;however,culture is not widely available.Therefore,a rifabutin based regimen could be the best solution.Rifabutin indeed shows a low rate of antibiotic resistance.Rifabutin is generally used in combination with amoxicillin in a triple therapy,with eradication rates about 80%in third-line regimens.The ideal duration of this therapy should range between 10 and 12 d.Combinations with antibiotics other than amoxicillin have demonstrated even better results,such as vonoprazan,which is a type of novel acid suppressor drug.Finally,a new formulation of triple therapy in a single capsule is under investigation,which is a field that deserves further investigation.Some notes of caution about rifabutin should be mentioned.This drug is used to treat tuberculosis or atypical mycobacteria;therefore,before starting a rifabutin-based eradication regimen,Mycobacterium tuberculosis infection should be thoroughly tested,since its use could promote the development of antibiotic resistance,thus affecting its effectiveness against Koch’s bacillus.Additionally,some serious side effects must be evaluated before starting any rifabutin-based therapy.Adverse effects include fever,nausea,vomiting and bone marrow suppression.For this reason,full blood count surveillance is required.

Lessons learned from the TIMI trials in rescue interventions for elderly patients after failed fibrinolytic therapy:look beyond the TIMI flow

In ST-segment elevation myocardial infarction (STEMI), acute reperfusion of the infarct-related artery (IRA)is the main goal in the early minutes after the patient seeks medical attention. Fibrinolytic therapy (FT) and/or primary coronary intervention (PCI) were proven to be effective in opening the IRA.

Older adults with acute severe ulcerative colitis have similar steroid non-response and colectomy rates as younger adults

BACKGROUND There is paucity of data on outcomes of acute severe ulcerative colitis(ASUC)in older adults(≥60 years of age).AIM To assess steroid non-response rates during the index admission for ASUC in older adults.Secondary outcomes were response to medical rescue therapy and colectomy rates;at index admission,3 and 12 mo.METHODS This retrospective multicentre cohort study included ASUC admissions who received intravenous steroids between January 2013 and July 2020 at two tertiary hospitals.Electronic medical records were reviewed to collect clinical,biochemical,and endoscopic data.A modified Poisson regression model was used for analysis.RESULTS Of 226 ASUC episodes,45(19.9%)occurred in patients≥60 years of age.Steroid non-response rates were comparable in older adults and patients<60 years of age[19(42.2%)vs 85(47%),P=0.618],crude risk ratio(RR)=0.89[95%confidence interval(CI):0.61-1.30],adjusted RR=0.99(0.44-2.21).Rates of response to medical rescue therapy in older adults was comparable to the younger cohort[76.5%vs 85.7%,P=0.46,crude RR=0.89(0.67-1.17)].Index admission colectomy[13.3%vs 10.5%,P=0.598,crude RR=1.27(0.53-2.99),adjusted RR=1.43(0.34-6.06)],colectomy at 3 mo[20%vs 16.6%,P=0.66,crude RR=1.18(0.61-2.3),adjusted RR=1.31(0.32-0.53)]and colectomy at 12 mo[20%vs 23.2%,P=0.682,crude RR=0.85(0.45-1.57),adjusted RR=1.21(0.29-4.97)],were similar between the two groups.CONCLUSION In older adults with ASUC,the steroid non-response rate,response to medical rescue therapy,and colectomy rate at index admission,3 and 12 mo is similar to patients less than 60 years of age.

Management of chronic hepatitis B infection: Current treatment guidelines, challenges, and new developments

Chronic hepatitis B(CHB)virus infection is a global public health problem,affecting more than 400 million people worldwide.The clinical spectrum is wide,ranging from a subclinical inactive carrier state,to progressive chronic hepatitis,cirrhosis,decompensation,and hepatocellular carcinoma.However,complications of hepatitis B virus(HBV)-related chronic liver disease may be reduced by viral suppression.Current international guidelines recommend first-line treatment of CHB infection with pegylated interferon,entecavir,or tenofovir,but the optimal treatment for an individualpatient is controversial.The indications for treatment are contentious,and increasing evidence suggests that HBV genotyping,as well as serial on-treatment measurements of hepatitis B surface antigen and HBV DNA kinetics should be used to predict antiviral treatment response.The likelihood of achieving a sustained virological response is also increased by extending treatment duration,and using combination therapy.Hence the paradigm for treatment of CHB is constantly evolving.This article summarizes the different indications for treatment,and systematically reviews the evidence for the efficacy of various antiviral agents.It further discusses the shortcomings of current guidelines,use of rescue therapy in drug-resistant strains of HBV,and highlights the promising clinical trials for emerging therapies in the pipeline.This concise overview presents an updated practical approach to guide the clinical management of CHB.

Helicobacter pylori:Management in 2013

Helicobacter pylori (H. pylori) is a prevalent, worldwide, chronic infection. Choice of treatment can be modified according to antibiotic-resistance rates of H. pylori. The ideal therapeutic regimen for H. pylori infection should achieve an eradication rate of &#x02265; 80%. In some countries, triple therapy with a proton-pump inhibitor (PPI), clarithromycin, and amoxicillin or metronidazole is still the best option. Bismuth-containing quadruple therapy consisting of bismuth salts, tetracycline, metronidazole and PPI, may be the preferred option in countries with clarithromycin resistance &#x0003e; 20%. Sequential therapy including a PPI and amoxicillin given for the first 5 d, followed by triple therapy including a PPI, clarithromycin, and nitroimidazole antimicrobial (all twice daily) for the remaining 5 d, can be another option for the first-line treatment of H. pylori. Recent data suggest that treatment with PPI, levofloxacin, and amoxicillin for 10 d is a good choice for second-line therapy. Concomitant therapy consisting of PPI, amoxicillin, clarithromycin and metronidazole is another option for second-line treatment. If second-line treatment also fails, it is recommended to culture H. pylori from biopsy specimens and perform antimicrobial susceptibility testing. Rescue treatment should be based on antimicrobial susceptibility.

Efficacy of a therapeutic strategy for eradication of Helicobacter pylori infection

AIM: To determine the efficacy of our therapeutic strategy for Helicobacter pylori (H. pylori) eradication and to identify predictive factors for successful eradication. METHODS: From April 2006 to June 2010, we retrospectively assessed 2428 consecutive patients (1025 men, 1403 women; mean age 55 years, age range 18-92 years) with gastric histology positive for H. pylori infection referred to our unit for 13-C urea breath test(UBT), after first-line therapy with proton pump inhibitor (PPI) b.i.d. + amoxicillin 1 g b.i.d. + clarithromycin 500 mg b.i.d. for 7 d. Patients who were still positive to UBT were recommended a second-line therapy (PPI b.i.d. + amoxicillin 1 g b.i.d. + tinidazole 500 mg b.i.d. for 14 d). Third choice treatment was empirical with PPI b.i.d. + amoxicillin 1 g b.i.d. + levofloxacin 250 mg b.i.d. for 14 d. RESULTS: Out of 614 patients, still H. pylori-positive after first-line therapy, only 326 and 19 patients respectively rechecked their H. pylori status by UBT after the suggested second and third-line regimens. "Per protocol" eradication rates for first, second and thirdline therapy were 74.7% (95% CI: 72.7%-76.4%), 85.3% (95% CI: 81.1%-89.1%) and 89.5% (95% CI: 74.9%-103%) respectively. The overall percentage of patients with H. pylori eradicated after two treatments was 97.8% (95% CI: 97.1%-98.4%), vs 99.9% (95% CI: 99.8%-100%) after three treatments. The study found that eradication therapy was most effective in patients with ulcer disease (P < 0.05, P = 0.028), especially in those with duodenal ulcer. Smoking habits did not significantly affect the eradication rate. CONCLUSION: First-line therapy with amoxicillin and clarithromycin produces an H. pylori eradication rate comparable or superior to other studies and secondline treatment can still be triple therapy with amoxicillin and tinidazole.

Do available data support the widespread adoption of pancreatoscopy guided-lithotripsy?

Peroral pancreatoscopy(POPS)is a demanding endoscopic procedure that can be used to perform intracanal lithotripsy in obstructing pancreatic stones but the experience is limited.Most stones can be removed successfully by endoscopic retrograde cholangio-pancreatography but patients with large stones require advanced therapeutic approaches,such as extracorporeal shock wave lithotripsy(alone or followed by endoscopic retrograde cholangio-pancreatography),currently the mainstay of treatment.Unfortunately,in about 10%of cases,extracorporeal shock wave lithotripsy can fail;moreover,it is not be available in many institutions.For this subgroup of patients,POPS guided-lithotripsy can play a role and have benefits.The most consistent study concerns a retrospective multicenter analysis that enrolled few patients per center.Considering the epidemiological scenario and the scant volume of skilled endoscopists,POPS must be developed in very few high-volume referral centers with standardized pathways and capable of performing multi-modality treatment.In addition,we could reasonably assume that POPS-guided-lithotripsy should be used as rescue therapy in special situations,identifying the ideal candidate who can achieve the maximum clinical result,and carefully balancing risk/benefits ratio.

Detection of Mutations Resistant to Lamivudine or Adefovir in HBV and Its Management

Objective Nucleos(t)ide analogues(NAs)na?ve chronic hepatitis B(CHB)patients were given rescue combination therapy after drug resistance to lamivudine or adefovir.Evolution of HBV mutation patterns and its impact on antiviral effects were studied.Methods Total of 142 na?ve CHB patients treated with lamivudine were randomly divided into two groups when lamivudine resistance occurred.One group was added with adefovir,the other was switched to entecavir and adefovir.Seventy-two na?ve CHB patients treated with adefovir were randomly divided into two groups when adefovir resistance occurred.One group was added with lamivudine,the other was added with entecavir.HBV polymerase reverse transcriptase mutations associated with resistance were analyed before and after 48weeks of rescue therapy,respectively.Results The mutation patterns of M204V/I,M204V+L180M were predominantly found in CHB patients after lamivudine resistance.Meanwhile,the entecavir resistance mutation patterns were also detected.Therefore,patients with lamivudine resistance could develop more diverse drug resistance mutations if they were switched to entecavir and adefovir.The mutation patterns of rtA181 were predominantly found in CHB patients after adefovir resistance and rescure therapy with add-on entecavir was more effective than with add-on lamivudine Conclusions Resistance mutation analysis chould help to choose NAs,reduce resistance and ehance antiviral effects.

Endovascular treatment of acute M1 occlusions due to underlying intracranial atherosclerotic severe stenosis

Background:Endovascular treatment(EVT)for acute ischemic stroke with an occlusion of the M1 segment due to intracranial atherosclerotic severe stenosis(ICASS)remains challenging.This study aimed to evaluate the safety and efficacy of EVT for ICASS-related M1 acute occlusion.Methods:We retrospectively reviewed all patients with an ICASS-related M1 acute occlusion who underwent EVT at our institution between January 2015 and December 2020.Clinical presentation,baseline characteristics,angiographic and clinical results,technical feasibility,perioperative complications,and follow-up results were evaluated.Results:Twenty-two patients with ICASS-related M1 acute occlusion were included.Eight patients(36.4%)received bridging therapy,and the other 14 patients(63.6%)directly underwent EVT.Fifteen patients(68.2%)treated with balloon dilations and stenting as rescue treatment.Six patients(27.3%)received single balloon angioplasty,and 5 of these patients were treated with staged stenting.One case(4.5%)failed recanalization at the first EVT,and successful revascularization was achieved a month later.The mean procedure time was 67.2±20.8 min.Successful revascularization(mTICI≥2b)was achieved in 95.5%(21/22)of patients.Perioperative complications developed in two patients(9.1%)including one hemorrhagic event and one thromboembolic event.Angiographic follow-up was available in 20 patients(90.9%)at an average of 8.6±3.0 months.The degree of stenosis was worse(10-30%)in 6 cases(30%)compared with the initial outcomes.The favorable outcomes(mRS≤2)at 3-month follow-up was achieved in 19 patients(86.4%).Conclusions:ICASS-related occlusion in the M1 segment often required a rescue therapy including balloon angioplasty with/without stenting,and this treatment strategy was safe and effective.But single balloon angioplasty at the first EVT generally cannot achieve satisfactory results and often needed staged stenting treatment.

Susceptibility-guided bismuth quadruple therapies for resistant Helicobacter pylori infections

Increasing Helicobacter pylori resistance to antibiotics has ledthat molecular testing is appropriate as a sub to adoption of seven different bismuth quadruple therapies(BQT)in China without differentiation of first-line or second-line regimens.The objective of this study was to evaluate the efficacy of susceptibility-guided BQT for patients who had experienced previous treatment failures.A total of 133 patients was included and H.pylori was successfully cultured from 101 patients(75.9%)for subsequent antimicrobial susceptibility testing(AST).Based on the AST results,88 patients completed one of five AST-guided 14-day BQT regimens:esomeprazole and bismuth colloidal pectin,along with either,amoxicillin and clarithromycin(EBAC),amoxicillin and levofloxacin(EBAL),amoxicillin and furazolidone(EBAF),amoxicillin and tetracycline(EBAT),or tetracycline and furazolidone(EBTF).H.pylori eradication rateswere 100%for EBAC(5/5),EBAL(13/13),EBAF(14/14),and EBTF(43/43),but 76.9%for EBAT(10/13).The three patients that failed the EBAT regimenwere all cured after subsequent treatment with the EBTF regimen.Our study demonstrates the excellent efficacy of the AST-guided BQT for referred H.pylori patients,and that the current EBAT regimen,used in clinics,needs to be optimized.In addition,57 of the isolates were subjected to whole-genome sequencing.Analysis of the sequences revealed that point mutations in 23S rRNA correlated well with the phenotypic clarithromycin resistance with a concordance of 91.2%,while the concordance between phenotypic levofloxacin resistance and gyrA point mutations was 82.3%.This suggests that molecular testing is appropriate as a substitute for AST as a more rapid and cost-effective method for determining clarithromycin and levofloxacin resistance in Chinese patients.