Systematic treatment in gastric cancer patients with overt bleeding:A propensity score matching analysis

BACKGROUND Hemorrhage,which is not a rare complication in patients with gastric cancer(GC)/gastroesophageal junction cancer(GEJC),can lead to a poor prognosis.However,no study has examined the effectiveness and safety of chemotherapy as an initial therapy for GC/GEJC patients with overt bleeding(OB).AIM To investigate the impact of OB on the survival and treatment-related adverse events(TRAEs)of GC/GEJC patients.METHODS Patients with advanced or metastatic GC/GEJC who received systematic treatment at Peking University Third Hospital were enrolled in this study.Propensity score matching(PSM)analysis was performed.RESULTS After 1:2 PSM analysis,93 patients were assessed,including 32 patients with OB before treatment(OBBT)and 61 patients without OBBT.The disease control rate was 90.6%in the group with OBBT and 88.5%in the group without OBBT,and this difference was not statistically significant.There was no difference in the incidence of TRAEs between the group with OBBT and the group without OBBT.The median overall survival(mOS)was 15.2 months for patients with OBBT and 23.7 months for those without OBBT[hazard ratio(HR)=1.101,95%confidence interval(CI):0.672-1.804,log rank P=0.701].The mOS was worse for patients with OB after treatment(OBAT)than for those without OBAT(11.4 months vs 23.7 months,HR=1.787,95%CI:1.006-3.175,log rank P=0.044).CONCLUSION The mOS for GC/GEJC patients with OBBT was similar to that for those without OBBT,but the mOS for patients with OBAT was worse than that for those without OBAT.

Research Progress of Radical Treatment of Helicobacter Pylori Based on Drug Sensitivity Test as First-Line Treatment

Helicobacter pylori (HP) infection is a global problem that affects about half of the world’s population and requires sufficient attention in clinical and scientific work. Due to differences in economic and medical conditions among countries around the world, there is currently no unified treatment plan for anti-HP. In China, empirical quadruple therapy is mainly used. With the abuse of antibiotics, many patients face the problem of secondary eradication after failure, and the resistance rate of HP is gradually increasing. After eradication failure, drug sensitivity cultivation is carried out to choose sensitive antibiotics for treatment. A new strategy is currently needed to address how to improve the eradication rate of HP during the first eradication. This article aims to discuss the first-line treatment plans and research progress for eradicating HP based on drug sensitivity testing before eradication. Compared with traditional empirical therapies, treatment based on drug sensitivity results can effectively improve the eradication rate of HP, and reduce drug resistance rates, and adverse reactions, among other benefits. .

First-line endoscopic treatment with over-the-scope clips significantly improves the primary failure and rebleeding rates in high-risk gastrointestinal bleeding: A single-center experience with 100 cases

AIM To evaluate rebleeding, primary failure(PF) and mortality of patients in whom over-the-scope clips(OTSCs) were used as first-line and second-line endoscopic treatment(FLET, SLET) of upper and lower gastrointestinal bleeding(UGIB, LGIB).METHODS A retrospective analysis of a prospectively collected database identified all patients with UGIB and LGIB in a tertiary endoscopic referral center of the University of Freiburg, Germany, from 04-2012 to 05-2016(n= 93) who underwent FLET and SLET with OTSCs. The complete Rockall risk scores were calculated from patients with UGIB. The scores were categorized as < or ≥ 7 and were compared with the original Rockall data. Differences between FLET and SLET were calculated. Univariate and multivariate analysis were performed to evaluate the factors that influenced rebleeding after OTSC placement.RESULTS Primary hemostasis and clinical success of bleeding lesions(without rebleeding) was achieved in 88/100(88%) and 78/100(78%), respectively. PF was significantly lower when OTSCs were applied as FLET compared to SLET(4.9% vs 23%, P = 0.008). In multivariate analysis, patients who had OTSC placement as SLET had a significantly higher rebleeding risk compared to those who had FLET(OR 5.3; P = 0.008). Patients with Rockall risk scores ≥ 7 had a significantly higher in-hospital mortality compared to those with scores < 7(35% vs 10%, P = 0.034). No significant differences were observed in patients with scores < or ≥ 7 in rebleeding and rebleeding-associated mortality.CONCLUSION Our data show for the first time that FLET with OTSC might be the best predictor to successfully prevent rebleeding of gastrointestinal bleeding compared to SLET. The type of treatment determines the success of primary hemostasis or primary failure.

Efficacy of the femoral neck system in femoral neck fracture treatment in adults: A systematic review and meta-analysis

BACKGROUND Controversy remains around the available choices for the internal fixation of a femoral neck fracture.The femoral neck system(FNS)was developed in 2018 and has been widely applied since then as it can provide rigid fixation stability with less damage to the bone mass around the fracture.However,no systematic reviews and meta-analyses have investigated the efficacy of the FNS in comparison with that of traditional internal fixation in the treatment of femoral fractures.AIM To assess the efficacy of the FNS in comparison with that of cannulated compression screws(CCS)in the treatment of femoral fractures through systematic review and meta-analysis.METHODS Five electronic databases(PubMed,Embase,Cochrane Central Register of Controlled Trials,China National Knowledge Infrastructure,and Wanfang)were searched from the earliest publication date to December 31,2021.Reference Citation Analysis(https://www.referencecitationanalysis.com/)was used to check the results and further analyze the related articles.Controlled trials were included if the FNS was applied for the femoral neck fracture in adults and if it was compared with CCS for the achievement of internal fixation.The measurement outcomes included the required operation time,observed patient’s blood loss,extent of fracture healing,patient’s Harris Hip score(HHS)at the last follow-up,and records of any complications(such as failure of internal fixation,femoral neck shortness,avascular necrosis of the femoral head,and delayed union or nonunion).RESULTS Ten retrospective controlled studies(involving 711 participants)were included in this metaanalysis.The meta-analysis showed that compared with CCS,use of the FNS could not decrease the operation time[standardized mean difference(SMD):-0.38,95%confidence interval(CI):-0.98 to 0.22,P=0.21,I2=93%),but it could increase the intraoperative blood loss(SMD:0.59,95%CI:0.15 to 1.03,P=0.009,I2=81%).The pooled results also showed that compared with CCS,the FNS could better promote fracture healing(SMD:-0.97,95%CI:-1.65 to-0.30,P=0.005,I2=91%),improve the HHS at the last follow-up(SMD:0.76,95%CI:0.31 to 1.21,P=0.0009,I2=84%),and reduce the chances of developing femoral neck shortness(OR:0.29,95%CI:0.14 to 0.61,P=0.001,I2=0%)and delayed union or nonunion(OR:0.47,95%CI:0.30 to 0.73,P=0.001;I2=0%)in adult patients with femoral neck fractures.However,there was no statistically significant difference between the FNS and CCS in terms of failure of internal fixation(OR:0.49,95%CI:0.23 to 1.06,P=0.07,I2=0%)and avascular necrosis of the femoral head(OR:0.46,95%CI:0.20 to 1.10,P=0.08,I2=0%).CONCLUSION Compared with CCS,the FNS could decrease the chances of developing femoral neck shortness and delayed union or nonunion in adults with femoral neck fractures.Simultaneously,it could accelerate fracture healing and improve the HHS in these patients.

Comparing the efficacy and safety of low,medium,and high dosages of selexipag for treating pulmonary hypertension:A systematic review and meta-analysis

Background:The maintenance dosage of selexipag is categorized as low,medium or high.In order to assess the efficacy and safety of different dosages of selexipag for the risk stratification of pulmonary arterial hypertension(PAH),we performed a sys-tematic review and meta-analysis.Methods:Studies assessing PAH risk stratification indices,such as the World Health Organization functional class(WHO-FC),six-minute walk distance(6MWD),N-terminal pro-B-type natriuretic peptide(NT-proBNP)level,right atrial pressure(RAP),cardiac index(CI)and mixed venous oxygen saturation(SvO2),were included.Results:Thirteen studies were included.Selexipag led to improvements in the 6MWD(MD:24.20 m,95%CI:10.74-37.67),NT-proBNP(SMD:-0.41,95%CI:-0.79-0.04),CI(MD:0.47 L/min/m^(2),95%CI:0.17-0.77)and WHO-FC(OR:0.564,95%CI:0.457-0.697).Subgroup analysis demonstrated that all three dosages improved the 6MWD.A moderate dosage led to improvements in the CI(MD:0.30 L/min/m^(2),95%CI:0.15-0.46)and WHO-FC(OR:0.589,95%CI:0.376-0.922).Within 6 months of treatment,only the WHO-FC and CI were significantly improved(OR:0.614,95%CI:0.380-0.993;MD:0.30 L/min/m^(2),95%CI:0.16-0.45,respectively).More than 6 months of treatment significantly improved the 6MWD,WHO-FC and NT-proBNP(MD:40.87 m,95%CI:10.97-70.77;OR:0.557,95%CI:0.440-0.705;SMD:-0.61,95%CI:-1.17-0.05,respectively).Conclusions:Low,medium,and high dosages of selexipag all exhibited good effects.When treatment lasted for more than 6 months,selexipag exerted obvious effects,even in the low-dosage group.This finding is important for guiding individualized treatments.

Predictive value of tumor-infiltrating lymphocytes for neoadjuvant therapy response in triple-negative breast cancer: A systematic review and meta-analysis

BACKGROUND The association between tumor-infiltrating lymphocyte(TIL)levels and the res-ponse to neoadjuvant therapy(NAT)in patients with triple-negative breast cancer(TNBC)remains unclear.AIM To investigate the predictive potential of TIL levels for the response to NAT in TNBC patients.METHODS A systematic search of the National Center for Biotechnology Information PubMed database was performed to collect relevant published literature prior to August 31,2023.The correlation between TIL levels and the NAT pathologic com-plete response(pCR)in TNBC patients was assessed using a systematic review and meta-analysis.Subgroup analysis,sensitivity analysis,and publication bias analysis were also conducted.RESULTS A total of 32 studies were included in this meta-analysis.The overall meta-ana-lysis results indicated that the pCR rate after NAT treatment in TNBC patients in the high TIL subgroup was significantly greater than that in patients in the low TIL subgroup(48.0%vs 27.7%)(risk ratio 2.01;95%confidence interval 1.77-2.29;P<0.001,I2=56%).Subgroup analysis revealed that the between-study hetero-geneity originated from differences in study design,TIL level cutoffs,and study populations.Publication bias could have existed in the included studies.The meta-analysis based on different NAT protocols revealed that all TNBC patients with high levels of TILs had a greater rate of pCR after NAT treatment in all protocols(all P≤0.01),and there was no significant between-protocol difference in the statistics among the different NAT protocols(P=0.29).Additionally,sensitivity analysis demonstrated that the overall results of the meta-analysis remained consistent when the included studies were individually excluded.CONCLUSION TILs can serve as a predictor of the response to NAT treatment in TNBC patients.TNBC patients with high levels of TILs exhibit a greater NAT pCR rate than those with low levels of TILs,and this predictive capability is con-sistent across different NAT regimens.

Combining GLP-1 receptor agonists and SGLT-2 inhibitors for cardiovascular disease prevention in type 2 diabetes:A systematic review with multiple network meta-regressions

BACKGROUND Glucagon-like peptide-1 receptor agonists(GLP-1RA)and sodium-glucose co-transporter-2 inhibitors(SGLT-2I)are associated with significant cardiovascular benefit in type 2 diabetes(T2D).However,GLP-1RA or SGLT-2I alone may not improve some cardiovascular outcomes in patients with prior cardiovascular co-morbidities.AIM To explore whether combining GLP-1RA and SGLT-2I can achieve additional benefit in preventing cardiovascular diseases in T2D.METHODS The systematic review was conducted according to PRISMA recommendations.The protocol was registered on PROSPERO(ID:42022385007).A total of 107049 participants from eligible cardiovascular outcomes trials of GLP-1RA and SGLT-2I were included in network meta-regressions to estimate cardiovascular benefit of the combination treatment.Effect modification of prior myocardial infarction(MI)and heart failure(HF)was also explored to provide clinical insight as to when the INTRODUCTION The macro-and micro-vascular benefits of glucagon-like peptide-1 receptor agonists(GLP-1RA)and sodium-glucose co-transporter-2 inhibitors(SGLT-2I)are independent of their glucose-lowering effects[1].In patients with type 2 diabetes(T2D),the major cardiovascular outcome trials(CVOT)showed that dipeptidyl peptidase-4 inhibitors(DPP-4I)did not improve cardiovascular outcomes[2],whereas cardiovascular benefit of GLP-1RA or SGLT-2I was significant[3,4].Further subgroup analyses indicated that the background cardiovascular risk should be considered when examining the cardiovascular outcomes of these newer glucose-lowering medications.For instance,prevention of major adverse cardiovascular events(MACE)was only seen in those patients with baseline atherosclerotic cardiovascular disease[3,4].Moreover,a series of CVOT conducted in patients with heart failure(HF)have demonstrated that(compared with placebo)SGLT-2I significantly reduced risk of hospitalization for HF or cardiovascular death,irrespective of their history of T2D[5-8].However,similar cardiovascular benefits were not observed in those with myocardial infarction(MI)[9,10].Cardiovascular co-morbidities are not only approximately twice as common but are also associated with dispropor-tionately worse cardiovascular outcomes in patients with T2D,compared to the general population[11].Therefore,it is of clinical importance to investigate whether the combination treatment of GLP-1RA and SGLT-2I could achieve greater cardiovascular benefit,particularly when considering patients with cardiovascular co-morbidities who may not gain sufficient cardiovascular protection from the monotherapies.This systematic review with multiple network meta-regressions was mainly aimed to explore whether combining GLP-1RA and SGLT-2I can provide additional cardiovascular benefit in T2D.Cardiovascular outcomes of these newer antidiabetic medications were also estimated under effect modification of prior cardiovascular diseases.This was to provide clinical insight as to when the combination treatment might be prioritized.

Sequential chemotherapy and icotinib as first-line treatment for advanced epidermal growth factor receptor-mutated non-small cell lung cancer

BACKGROUND Icotinib could have potential effect and tolerability when used sequentially with chemotherapy for advanced epidermal growth factor receptor(EGFR)-mutated non-small cell lung cancer(NSCLC).AIM To evaluate the efficacy and safety of chemotherapy followed by icotinib maintenance therapy as first-line treatment for advanced EGFR-mutated NSCLC.METHODS This multicenter,open-label,pilot randomized controlled trial enrolled 68 EGFRmutated stage IIIB/IV NSCLC patients randomized 2:3 to the icotinib alone and chemotherapy+icotinib groups.RESULTS The median progression-free survival in the icotinib alone and chemotherapy+icotinib groups was 8.0 mo(95%CI:3.84-11.63)and 13.4 mo(95%CI:10.18-16.33),respectively(P=0.0249).No significant differences were found in the curative effect when considering different cycles of chemotherapy or chemotherapy regimen(all P>0.05).CONCLUSION A sequential combination of chemotherapy and EGFR-tyrosine kinase inhibitor is feasible for stage IV EGFR-mutated NSCLC patients.

Efficacy of gefitinib as a first-line single agent treatment in patients with advanced non-small cell lung cancer

Objective： To assess the efficacy and toxicity of gefitinib as a single agent treatment in Chinese patients with advanced non-small cell lung cancer （NSCLC）. Methods： Forty-five patients with advanced NSCLC were treated with gefitinib at 250 mg daily until the disease progressed or the patient could not tolerate the toxicity. Results： None of the patients achieved a complete response （CR）, while 15 patients achieved a partial remission （PR） and 17 experienced a stable disease （SD）. Thirteen patients continued to have a progressive disease （PD）. The response rate and the disease control rate were 33.3% and 71.1%, respectively. The symptom remission rate was 72.5%, and the median remission time was 8 days. The median survival time was 15.3 months. The median progression-free survival time was 6.0 months. The most common toxicities included rash （53.3%） and diarrhea （33.3%）. Dehydration and pruritus of the skin developed in 26.7% and 22.2% of the patients, respectively. Hepatic toxicity occurred in 6.7% of patients and oral ulceration occurred in 4.4% of patients. Conclusion： Single agent treatment with gefitinib is effective against advanced NSCLC, and is well tolerated in Chinese patients.

Treatment options for rumination syndrome: A systematic review

BACKGROUND Rumination syndrome (RS) is characterized by recurrent effortless postprandial regurgitation of recently ingested food from the stomach to the oral cavity and has been associated with quality of life impairment and malnutrition. There is a general lack of consensus on the most appropriate treatment options for RS. AIM To summarize the literature on treatment options for RS. METHODS We conducted a systematic review according to PRISMA guidelines. We searched Medline (1946 to February 2019), EMBASE (1947 to February 2019), PsycINFO (1806 to February 2019) and Cochrane central register of controlled trials for articles discussing treatment options for adult patients (> 18 years) with RS. All relevant articles were accessed in full text. We extracted data on study designs, patient profiles, duration of symptoms, follow up periods, date, diagnostic criteria, interventions and outcomes. Risk of bias assessment was carried out independently by 3 reviewers via Cochrane Risk of Bias tool and Newcastle Ottawa Scale for randomized controlled trials and Cohort studies respectively. RESULTS Twelve articles were identified. A total of 254 patients were included in the analysis, with a mean age of 36.1 (range 18-89). 185 patients (72.8%) were females. 5 studies looked into behavioral therapies, primarily diaphragmatic breathing (DB) 2 studies looked at baclofen, 1 fundoplication and 1 supportive lifestyle changes. 3 studies looked at a combination of therapies involving pharmacological, behavioral and psychotherapies. CONCLUSION Although evidence for treatment options is still limited, the strongest evidence point towards the use of DB and Baclofen, and both should be considered depending on their availabilities.

A Radiotherapy Treatment Margin Formula When Systematic Positioning Errors are Relatively Small Compared to Random Positioning Errors: A First-Order Approximation

A radiotherapy treatment margin formula has been analytically derived when a standard deviation (SD) of systematic positioning errors &#425;is relatively small compared to an SD of random positioning errors &sigma;. The margin formula for 0 ≤ &#425;≤ &sigma;was calculated by linearly interpolating two boundaries at &#425;= 0 and &#425;= &sigma;, assuming that the van Herk margin approximation of k1&#425;+ k2&sigma;is valid at &#425;= &sigma;. It was shown that a margin formula for 0 ≤ &#425;≤ &sigma;may be approximated by k1&sigma;+ k2&#425;, leading to a more general form of k1 max(&#425;,&sigma;) + k2 min(&#425;,&sigma;) which is a piecewise linear approximation for any values of &#425;and &sigma;.

Treatment failure and associated factors among first line patients on highly active antiretroviral therapy in Ethiopia:a systematic review and meta-analysis

Background:Antiretroviral therapy(ART)restores immune function and reduces human immunodeficiency virus(HIV)related adverse outcomes.The results of previous studies in Ethiopia were replete with inconsistent findings;nonexistence of national representative figures and determinant factors are found as significant gap.The aim of this systematic review and meta-analysis was to assess the existing evidence on ART treatment failure and associated factors in Ethiopia.Methods:Relevant studies on ART treatment failure were retrieved from international databases:PubMed,Google Scholar,Scopus,and Science Direct systematically prior to March 14,2019.All identified studies reporting the proportion of first line treatment failure among HIV patients in Ethiopia were included.Two authors independently extracted all necessary data using a standardized data extraction format.A random-effects model was used to calculate pooled estimates and associated factors in Stata/se Version-14.The Cochrane Q test statistics and I2 tests were used to assess the heterogeneity of the studies.Results:From 18 articles reviewed;the pooled proportion of first line treatment failure among ART users in Ethiopia was 15.3%(95%CI:12,18.6)with(I2=97.9%,p<0.001).The subgroup analysis by World Health Organization(WHO)treatment failure assessment criteria were carried out,accordingly the highest prevalence(11.5%)was noted on immunological and the lowest(5.8%)was observed virological treatment failure.We had found poor adherence(OR=8.6,95%CI:5.6,13.4),not disclosed(OR=2.1,95%CI:1.5,3.0),advanced WHO clinical stage III/IV(OR=2.4,95%CI:1.5,3.8),change in regimen(OR=2.5,95%CI:1.6,3.9)and being co-infected(OR=2.56,95%CI:2.2,3.0)were statistically significant factors for treatment failure.Conclusion:In this study,treatment failure among ART users in Ethiopia was significant.Adherence,co-infection,advanced WHO clinical stage,regimen change,and disclosure are determinant factors for treatment failure.Therefore,improve drug adherence,prevent co-infection,close follow up,and prevent HIV-drug resistance are required in future remedial efforts.

Ketoconazole Associated Hepatotoxicity: A Systematic Review and Metaanalysis

Objective To evaluate the incidence of Ketoconazole associated hepatotoxicity and related factors Methods Literature retrieval was conducted by using multi-databases for meta-analysis on Ketoconazole associated hepatotoxicity. The data were collected with a standardized form. Overall estimation of incidence of hepatotoxicity for specific study type was calculated by using a DerSimonian-Laird random-effects model owing to the substantial differences among the studies. Results Totally 204 eligible studies were included in the analysis. The incidence of Ketoconazole associated hepatotoxicity was 3.6%-4.2%. The dosage and duration specific subgroup analyses did not show any significant difference among groups, while the age specific subgroup analysis showed the incidence in children and people aged 〉60 years was 1.4% （95% CI 0.5%-4.2%） and 3.2% （95% Cl： 1.1%-8.7%） respectively. Additionally, the incidence of the hepatotoxicity was higher in people who had oral administration of ketoconazole beyond the provisions of the usage instructions, and the incidence was 5.7% （95% CI： 4.5%-7.2%）. Conclusion Ketoconazole associated hepatotoxicity was common. Off-label use might increase the risk of liver damage. Well-designed large sample studies are needed to identify the risk factors in future.

Clinical guidelines of non-alcoholic fatty liver disease: A systematic review

AIM To perform a systematic review to grade guidelines and present recommendations for clinical management of non-alcoholic fatty liver disease(NAFLD).METHODS A database search was conducted on Pub Med for guidelines published before May 2016, supplemented by reviewing relevant websites. The Appraisal of Guidelines for Research and Evaluation(ARGEE) instrument Ⅱ was a tool designed to appraise the methodological rigor and transparency in which a clinical guideline is developed and it is used internationally. it was used to appraise the quality of guidelines in this study. The inclusion criteria include: clinical NAFLD guidelines for adults, published in English, and released by governmental agencies or key organizations.RESULTS Eleven guidelines were included in this study. Since 2007, guidelines have been released in Asia(3 in China, 1 in South Korea, and 1 in Japan), Europe(1 in italy),America(1 in United States and 1 in Chile) and three international agencies [European associations joint, Asia-Pacific Working Party and World Gastroenterology Organization(WGO)]. Using the ARGEE Ⅱ instrument, we found US 2012 and Europe 2016 had the highest scores, especially in the areas of rigor of development and applicability. Additionally, italy 2010 and Korea 2013 also presented comprehensive content, rigorous procedures and good applicability. And WGO 2014 offered various algorithms for clinical practice. Lastly, a practical algorithm for the clinical management was developed, based on the recommended guidelines.CONCLUSION This is the first systematic review of NAFLD guidelines. it may yield insights for physicians and policy-makers in the development and application of guidelines.

Burden and outcomes for complex perianal fistulas in Crohn's disease:Systematic review

AIM To systematically review the literature on epidemiology,disease burden, and treatment outcomes for Crohn's disease(CD) patients with complex perianal fistulas.METHODS PubMed, Embase, and Cochrane were searched for relevant articles(published 2000-November 2016) and congress abstracts(published 2011-November 2016).RESULTS Of 535 records reviewed, 62 relevant sources were identified(mostly small observational studies). The cumulative incidence of complex perianal fistulas in CD from two referral-centre studies was 12%-14%(follow-up time, 12 years in one study; not reported in the second study). Complex perianal fistulas result in greatly diminished quality of life; up to 59% of patients are at risk of faecal incontinence. Treatments include combinations of medical and surgical interventions and expanded allogeneic adipose-derived stem cells. High proportions of patients experience lack of or inadequate response to treatment(failure and relapse rates,respectively: medical, 12%-73% and 0%-41%; surgical:0%-100% and 11%.20%; combined medical/surgical:0%-80% and 0%-50%; stem cells: 29%-47% and not reported). Few studies(1 of infliximab; 3 of surgical interventions)have been conducted in treatment-refractory patients, a population with high unmet needs. Limited data exist on the clinical value of anti-tumour necrosis factor-α dose escalation in patients with complex perianal fistulas in CD.CONCLUSION Complex perianal fistulas in CD pose substantial clinical and humanistic burden. There is a need for effective treatments, especially for patients refractory to antitumour necrosis factor-α agents, as evidenced by high failure and relapse rates.

Efficacy of moxifloxacin-based sequential and hybrid therapy for first-line Helicobacter pylori eradication

AIM: To evaluate the efficacy of moxifloxacin-based sequential therapy(MBST) versus hybrid therapy as a first-line treatment for Helicobacter pylori(H. pylori) infection.METHODS: From August 2014 to January 2015, 284 patients with confirmed H. pylori infection were randomized to receive a 14-d course of MBST(MBST group, n = 140) or hybrid(Hybrid group, n = 144) therapy. The MBST group received 20 mg rabeprazole and 1 g amoxicillin twice daily for 7 d, followed by 20 mg rabeprazole and 500 mg metronidazole twice daily, and 400 mg moxifloxacin once daily for 7 d. The Hybrid group received 20 mg rabeprazole and 1 g amoxicillin twice daily for 14 d. In addition, the Hybrid group received 500 mg metronidazole and 500 mg clarithromycin twice daily for the final 7 d. Successful eradication of H. pylori infection was defined as a negative 13C-urea breath test 4 wk after the end of treatment. Patient compliance was defined as "good" if drug intake was at least 85%. H. pylori eradication rates, patient compliance with treatment, and adverse event rates were evaluated.RESULTS: The eradication rates in the intention-totreat(ITT) analysis were 91.4%(128/140; 95%CI: 90.2%-92.9%) in the MBST group and 79.2%(114/144; 95%CI: 77.3%-80.7%) in the Hybrid group(P = 0.013). The eradication rates in the perprotocol(PP) analysis were 94.1%(128/136; 95%CI: 92.9%-95.6%) in the MBST group and 82.6%(114/138; 95%CI: 80.6%-84.1%) in the Hybrid group(P = 0.003). The H. pylori eradication rate in the MBST group was significantly higher than that of the Hybrid group for both the ITT(P = 0.013) and the PP analyses(P = 0.003). Both groups exhibited full compliance with treatment(MBST/Hybrid group: 100%/100%). The rate of adverse events was 11.8%(16/136) and 19.6%(27/138) in the MBST and Hybrid group, respectively(P = 0.019). The majority of adverse events were mild-to-moderate in intensity; none were severe enough to cause discontinuation of treatment in either group.CONCLUSION: MBST was more effective and led to fewer adverse events than hybrid therapy as a first-line treatment for H. pylori infection.

Non-bismuth quadruple therapy for first-line Helicobacter pylori eradication:A randomized study in Japan

AIM:To find the way to improve the eradication rate of first-line therapy in Japanese patients.METHODS:We prospectively compared the effectiveness of 7-d quadruple therapy to standard 7 d triple therapy in Japanese patients infected with Helicobacter pylori(H.pylori).One hundred and nineteen patients were randomly assigned to receive 7-d non-bismuth quadruple therapy with lansoprazole,amoxicillin,clarithromycin and metronidazole(LACM7) or 7-d triple therapy with lansoprazole,amoxicillin and clarithromycin(LAC7).After three months,H.pylori status was analyzed by 13C-urea breath test.Incidence rates of adverse events were evaluated by use of questionnaires.RESULTS:By intention-to-treat(ITT) analysis,the eradication rate in the LACM7 group was 94.9%,which was significantly higher than the LAC7 group(68.3%,P < 0.001).Per protocol analysis also showed a significantly higher eradication rate in the LACM7 group(98.3%) than the LAC7 group(73.2%,P < 0.001).Nevertheless,the incidence of serious adverse events did not differ between the two groups(RR:1.10,95% CI:0.70-1.73,P = 0.67).CONCLUSION:Seven day non-bismuth quadruple therapy(LACM7) was superior to standard 7-d triple therapy(LAC7) for first-line eradication.

Ranibizumab alone or in combination with photodynamic therapy vs photodynamic therapy for polypoidal choroidal vasculopathy: a systematic review and Meta-analysis

AIMTo compare the efficacy of intravitreal ranibizumab (IVR) alone or in combination with photodynamic therapy (PDT) vs PDT in patients with symptomatic polypoidal choroidal vasculopathy (PCV).METHODSA systematic search of a wide range of databases (including PubMed, EMBASE, Cochrane Library and Web of Science) was searched to identify relevant studies. Both randomized controlled trials (RCTs) and non-RCT studies were included. Methodological quality of included literatures was evaluated according to the Newcastle-Ottawa Scale. RevMan 5.2.7 software was used to do the Meta-analysis.RESULTSThree RCTs and 6 retrospective studies were included. The results showed that PDT monotherapy had a significantly higher proportion in patients who achieved complete regression of polyps than IVR monotherapy at months 3, 6, and 12 (All P&#x02264;0.01), respectively. However, IVR had a tendency to be more effective in improving vision on the basis of RCTs. The proportion of patients who gained complete regression of polyps revealed that there was no significant difference between the combination treatment and PDT monotherapy. The mean change of best-corrected visual acuity (BCVA) from baseline showed that the combination treatment had significant superiority in improving vision vs PDT monotherapy at months 3, 6 and 24 (All P&#x0003c;0.05), respectively. In the mean time, this comparison result was also significant at month 12 (P&#x0003c;0.01) after removal of a heterogeneous study.CONCLUSIONIVR has non-inferiority compare with PDT either in stabilizing or in improving vision, although it can hardly promote the regression of polyps. The combination treatment of PDT and IVR can exert a synergistic effect on regressing polyps and on maintaining or improving visual acuity. Thus, it can be the first-line therapy for PCV.

Effectiveness of non-pyrimethamine-based regimens for toxoplasma encephalitis:A systematic and meta-synthesis study

Objective:To examine the differences in effectiveness and side effects between pyrimethamine-based and non-pyrimethamine-based regimens for toxoplasma encephalitis since the availability of pyrimethamine in Indonesia is currently limited due to its withdrawal from the market.Methods:A systematic review and meta-synthesis study that was carried out by following a protocol guided by the Preffered Reporting Items for Systematic Review and Meta-analysis(PRISMA).Effectiveness measures included clinical improvement,mortality,and radiological improvement.We evaluated selected articles narratively because of the limitations of homogeneity.The risk of bias in RCTs was assessed using the Cochrane Risk of Bias tool for RCT(ROB 2.0)and cohort studies were assessed using the Risk of Bias In Non-Randomized Studies of Interventions(ROBINS-1)tool.Research quality was assessed using the GradePro software.Results:We included two retrospective cohort studies and one RCT.Narrative outcome assessment in these three studies did not show significant difference in effectiveness between pyrimethamine-based and non-pyrimethamine-based regimens for toxoplasma encephalitis treatment.However,drug side effects were consistently higher in the pyrimethamine-based regimen.Conclusions:This study has a high risk of bias.The quality of the research also has a low recommendation value.However,the results may be considered for application if a standard regimen is not available.

Combining of chemotherapy with targeted therapy for advanced biliary tract cancer:A systematic review and meta-analysis

BACKGROUND Targeted therapy(TT)has resulted in controversial efficacy as first-line treatment for biliary tract cancer(BTC).More efficacy comparisons are required to clarify the overall effects of chemotherapy(CT)combined with TT and CT alone on advanced BTC.AIM To conduct a meta-analysis of the available evidence on the efficacy of CT combined with TT for advanced BTC.METHODS The PubMed,EMBASE,ClinicalTrials,Scopus and Cochrane Library databases were systematically searched for relevant studies published from inception to August 2022.Only randomized clinical trials(RCTs)including comparisons between the combination of gemcitabine-based CT with TT and CT alone as firstline treatment for advanced BTC were eligible(PROSPERO-CRD42022313001).The odds ratios(ORs)for the objective response rate(ORR)and hazard ratios(HRs)for both progression-free survival(PFS)and overall survival(OS)were calculated and analyzed.Subgroup analyses based on different targeted agents,CT regimens and tumor locations were prespecified.RESULTS Nine RCTs with a total of 1361 individuals were included and analyzed.The overall analysis showed a significant improvement in ORR in patients treated with CT+TT compared to those treated with CT alone(OR=1.43,95%CI:1.11-1.86,P=0.007)but no difference in PFS or OS.Similar trends were observed in the subgroup treated with agents targeting epidermal growth factor receptor(OR=1.67,95%CI:1.17-2.37,P=0.004)but not in the subgroups treated with agents targeting vascular endothelial growth factor receptor or mesenchymal-epithelial transition factor.Notably,patients who received a CT regimen of gemcitabine+oxaliplatin in the CT+TT arm had both a higher ORR(OR=1.75,95%CI:1.20-2.56,P=0.004)and longer PFS(HR=0.83,95%CI:0.70-0.99,P=0.03)than those in the CT-only arm.Moreover,patients with cholangiocarcinoma treated with CT+TT had significantly increased ORR and PFS(ORR,OR=2.06,95%CI:1.27-3.35,PFS,HR=0.79,95%CI:0.66-0.94).CONCLUSION CT+TT is a potential first-line treatment for advanced BTC that leads to improved tumor control and survival outcomes,and highlighting the importance of CT regimens and tumor types in the application of TT.