BACKGROUND Effective acid suppression significantly enhances the eradication rate of Helicobacter pylori(H.pylori).AIM To assess the efficacy and safety of high-dose dual therapy(HDDT)utilizing various highly potent a...BACKGROUND Effective acid suppression significantly enhances the eradication rate of Helicobacter pylori(H.pylori).AIM To assess the efficacy and safety of high-dose dual therapy(HDDT)utilizing various highly potent antisecretory medications,thereby providing additional clinical guidance for H.pylori eradication.METHODS The study population comprised untreated H.pylori patients from three medical centers in central China.From February 10,2024 to March 31,2024,439 subjects were randomly allocated to either the esomeprazole-amoxicillin(EA)or esomeprazole-amoxicillin-clarithromycin-bismuth(B-quadruple)group.Subsequently,from April 1,2024 to May 10,2024,367 subjects were randomly assigned to either the vonoprazan-amoxicillin(VA)or vonoprazan-amoxicillin-clarithromycin(VAC)group.The study recorded treatment efficacy,adverse events,compliance,symptom alleviation,and associated costs.RESULTS EA-dual demonstrated non-inferiority to B-quadruple regimen in modified intention-to-treat(mITT)and perprotocol(PP)analyses(P<0.025).However,the eradication rate of EA was lower than that of the B-quadruple group[70.59%vs 83.49%,92.86%vs 98.38%,93.94%vs 98.38%,intention-to-treat(ITT),mITT,PP respectively,P<0.05].In ITT,mITT,and PP analyses,VA-dual was non-inferior to VAC treatment(84.15%vs 83.15%,96.25%vs 92.73%,96.75%vs 93.75%,P<0.025).No significant differences were observed in adverse events,compliance,and symptom relief between groups.VA exhibited the lowest cost.Antibiotic use within 2 years,poor compliance,and suburban residence were associated with reduced eradication efficacy(P<0.05).CONCLUSION The HDDT based on vonoprazan demonstrated non-inferiority to the VAC triple regimen,suggesting its potential as a recommended first-line treatment for H.pylori eradication.While B-quadruple therapy showed better eradication rate than EA therapy,the latter proved non-inferior in mITT and PP analyses.Notably,antibiotic use within the preceding two years,adherence to treatment protocols,and patient residence emerged as critical factors influencing eradication success.展开更多
BACKGROUND Occult hepatitis B virus infection(OBI)is defined by the detection of replication-competent hepatitis B virus(HBV)DNA in the liver and/or blood despite the ab-sence of detectable hepatitis B surface antigen...BACKGROUND Occult hepatitis B virus infection(OBI)is defined by the detection of replication-competent hepatitis B virus(HBV)DNA in the liver and/or blood despite the ab-sence of detectable hepatitis B surface antigen(HBsAg)using conventional ser-ological assays.Although OBI has been well-documented in individuals with resolved HBV infection or those receiving immunosuppressive therapy,reports of its occurrence during sequential antiviral treatment remain scarce.This report describes a case of chronic hepatitis B(CHB)transitioning through OBI during sequential combination therapy before ultimately achieving a functional cure.This case provides new insights into the emergence of OBI as a transitional phase during CHB treatment and emphasizes the importance of monitoring its clinical significance.CASE SUMMARY A 33-year-old Chinese male was diagnosed with HBV infection in 2001.The patient first presented in 2012 with abnormal liver function tests and received initial treatment with conventional interferon therapy,which failed to achieve a virological response.Antiviral therapy was subsequently switched to entecavir monotherapy.By August 2019,the patient exhibited an HBsAg level of 29.93 IU/mL with undetectable HBV DNA(<25 IU/mL).At this point,combination therapy with entecavir and pegylated interferonα(PEG-IFNα)was initiated.Remarkably,while HBsAg declined to 0.42 IU/mL by April 2020,a paradoxical HBV DNA rebound to 173 IU/mL was observed.The regimen was consequently modified to tenofovir alafenamide and PEG-IFNα.By October 2020,the patient achieved HBsAg seroconversion(HBsAg 0.01 IU/mL,hepatitis B surface antibody 52.18 mIU/mL)for the first time,while maintaining low-level viremia(37 IU/mL),consistent with transition to OBI.The patient was then switched to PEG-IFNαmonotherapy.In November 2021,he discontinued PEG-IFNαtherapy,and one month later,both HBV DNA(<10 IU/mL)and HBsAg(<0.05 IU/mL)were negative.This response has been sustained through follow-up.CONCLUSION This case study illustrates the efficacy of sequential combination therapy in achieving functional cure in CHB patients,including those with a prolonged infection history.It highlights OBI as a transitional yet underrecognized phase during sequential antiviral therapy.While the patient ultimately achieved functional cure,the transient persistence of HBV DNA despite HBsAg clearance suggests the need for continued monitoring.This case provides new insights into OBI development during treatment and underscores the importance of further research into its long-term implications.展开更多
AIM: To compare the effectiveness of standard triple, bismuth pectin quadruple and sequential therapies for Helicobacter pylori (H. pylori ) eradication in a randomized, double-blinded, comparative clinical trial in C...AIM: To compare the effectiveness of standard triple, bismuth pectin quadruple and sequential therapies for Helicobacter pylori (H. pylori ) eradication in a randomized, double-blinded, comparative clinical trial in China. METHODS: A total of 215 H. pylori -positive patients were enrolled in the study and randomly allocated into three groups: group A (n = 72) received a 10-d bismuth pectin quadruple therapy (20 mg rabeprazole bid , 1000 mg amoxicillin bid , 100 mg bismuth pectin qid , and 500 mg levofloxacin qd ); group B (n = 72) received the sequential therapy (20 mg omeprazole bid , 1000 mg amoxicillin bid , in 5 d, followed by 20 mg omeprazole bid , 500 mg tinidazole bid , 500 mg clarithromycin bid , for another 5 d); group C (n = 71) received a standard 1-wk triple therapy (20 mg omeprazole bid , 1000 mg amoxicillin bid , 500 mg clarithromycin bid ). After all these treatments, 20 mg omeprazole bid was administrated for 3 wk. H. pylori status was assessed by histology, 13C-urea breath test and rapid urease test at baseline and 4-6 wk after completion of treatment. Ulcer cicatrization was assessed by gastroscopy. χ 2 test (P < 0.05) was used to compare the eradication rates and ulcer cicatrisation rates among the three groups. RESULTS: The eradication rate was 83.33% (60/72) in group A, 88.89% (64/72) in group B, and 80.56% (58/71) in group C. The ulcer cicatrisation rate was 86.44% (51/59) in group A, 90.16% (55/61) in group B, and 84.91% (45/53) in group C. The sequential therapy yielded a higher eradication rate and ulcer cicatrisation rate than the standard triple and bismuth pectin quadruple therapies. Statistically, the eradication rate of group B was significantly different from groups A and C (P < 0.05), but the difference of ulcer cicatrisation rate and side effects was not statistically significant among the three groups (P > 0.05). The three protocols were generally well tolerated. CONCLUSION: The sequential therapy has achieved a significantly higher eradication rate, and is a more suitable first-line alternative protocol for anti-H. pylori infection compared with the standard triple and bismuth pectin quadruple therapies.展开更多
AIM: To compare hybrid therapy(HT) with traditional sequential therapy(ST) and concomitant therapy(CT) for Helicobacter pylori(H. pylori) eradication.METHODS: We performed an electronic search of Pub Med, Embase, and ...AIM: To compare hybrid therapy(HT) with traditional sequential therapy(ST) and concomitant therapy(CT) for Helicobacter pylori(H. pylori) eradication.METHODS: We performed an electronic search of Pub Med, Embase, and the CENTRAL database. Randomized controlled trials(RCTs) of HT were included in the meta-analysis. The primary outcome was the eradication rate of H. pylori. The secondary outcomes included the compliance rate and adverse event rate. Effect estimates were pooled using the random-effects model.RESULTS: Twelve studies were included. Pooled results showed no significant differences in eradication rate between HT and ST in per-protocol(PP) analysis(RR = 1.03, 95%CI: 0.94-1.12, P = 0.59) or in intention-totreat(ITT) analysis(RR = 1.00, 95%CI: 0.89-1.12, P = 0.94). HT and ST showed similarly high compliance rate(96% vs 98%, P = 0.55) and acceptable adverse event rate(30.3% vs 28.2%, P = 0.63). No significant results were seen in the eradication rate between HT and CT in PP analysis(RR = 1.01, 95%CI: 0.96-1.05, P = 0.76) or in ITT analysis(RR = 0.99, 95%CI: 0.95-1.03, P = 0.47). HT displayed a slightly higher compliance rate than CT(95.8% vs 93.2%, P < 0.05). The adverse event rates of HT and CT were similar(39.5% vs 44.2%, P = 0.24).CONCLUSION: Compared with ST or CT, HT yields a similar eradication rate, high compliance rate, and acceptable safety profiles.展开更多
Objective: Crizotinib is recommended as the first-line therapy for advanced anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC). Despite its initial efficacy, patients ultimately acquire resista...Objective: Crizotinib is recommended as the first-line therapy for advanced anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC). Despite its initial efficacy, patients ultimately acquire resistance to crizotinib within 1 year. In such patients, the optimal sequential therapy after crizotinib treatment remains unknown. This study explored which sequential therapy option confers the greatest benefit.Methods: A total of 138 patients with advanced ALK-positive NSCLC resistant to crizotinib were studied. Based on patterns of disease progression of metastases, patients were divided into 3 groups: brain progression, non-liver progression, and liver progression. Sequential therapies included crizotinib continuation plus local therapy, nextgeneration ALK inhibitors(ALKi's), and chemotherapy. The primary endpoint was overall survival(OS) from the time of crizotinib resistance to death or last follow-up.Results: The 138 patients included 64 cases with progression in brain, 57 cases in non-liver sites and 17 cases in liver. A significant difference in OS was observed among the distinct progression pattern(median OS, 25.4 months in brain, 15.8 months in non-liver, and 10.8 months in liver, respectively, P=0.020). The difference in OS among sequential therapies was statistically significant in the non-liver progression group(median OS, 27.6 months with next-generation ALKi's, 13.3 months with crizotinib continuation, and 10.8 months with chemotherapy,respectively, P=0.019). However, crizotinib continuation plus local therapy seems to provide non-inferior median OS compared with next-generation ALKi's for patients with brain progression(median OS, 28.9 months vs.32.8 months, P=0.204). And no significant differences in OS were found in patients with progression in liver(P=0.061).Conclusions: Crizotinib continuation together with local therapy might be a feasible strategy for patients with progression in brain beyond crizotinib resistance, as well as next-generation ALKi's. Next-generation ALKi's tended to provide a survival benefit in patients with non-liver progression.展开更多
AIM: To evaluate the efficacy and safety of modified sequential therapy and to compare modified sequential therapy with standard quadruple therapy for Helicobacter pylori(H. pylori) eradication.METHODS: In total, 200 ...AIM: To evaluate the efficacy and safety of modified sequential therapy and to compare modified sequential therapy with standard quadruple therapy for Helicobacter pylori(H. pylori) eradication.METHODS: In total, 200 consecutive patients who were diagnosed with H. pylori-infected chronic gastritis by electronic endoscopy and rapid urease testing from December 2012 to October 2013 were enrolled in this study. The patients had not previously received H. pylori eradication treatment, and were randomized into two groups. The patients in Group A(n = 101) were treated with ilaprazole + bismuth potassium citrate + amoxicillin and clavulanate potassium + levofloxacin, and the patients in Group B(n = 99) were administered a modified sequential therapy composed of ilaprazole at 5 mg bid and amoxicillin and clavulanate potassium at 914 mg for the first five days followed by ilaprazole at 5 mg bid, furazolidone at 100 mg bid and levofloxacin at 500 mg qid for the next five days. Four to six weeks after the end of treatment, a 14C-urea breath test was performed for all the subjects to confirm the eradication of H. pylori. The intention-to-treat and per-protocol eradication rates were determined.RESULTS: A total of 190 of the 200 patients completed the study. All 200 patients were included in the intention-to-treat analysis, whereas 190 patients were included in the per-protocol analysis. In the intentionto-treat analysis, the rates of H. pylori eradication in Groups A and B were 85.15%(86/101) and 81.82%(81/99), respectively. In the per-protocol analysis, the H. pylori eradication rates in Groups A and B were 88.66%(86/97) and 87.09%(81/93), respectively. No significant difference was observed(χ2 = 0.109, P = 0.741) in the eradication rate between Groups A and B. The rates of adverse effects observed in the groups were similar at 6.19%(6/97) for Group A and 7.53%(7/93) for Group B(P > 0.05). No mortality or major morbidities were observed in any of the patients. Symptomatic improvements in the presentation of stomachache, acid regurgitation, and burning sensation were not significantly different between the two groups.CONCLUSION: Ilaprazole-based 10-d standard quadruple therapy does not offer an incremental benefit over modified sequential therapy for the treatment of H. pylori infection, as both treatment regimens appear to be effective, safe, and well-tolerated as initial treatment options.展开更多
AIM: To evaluate the efficacy of sequential vs hybrid therapy in patients with Helicobacter pylori(H. pylori) infection.METHODS: From March 2013 to May 2014,one hundred and seventy-five H. pylori infected patients who...AIM: To evaluate the efficacy of sequential vs hybrid therapy in patients with Helicobacter pylori(H. pylori) infection.METHODS: From March 2013 to May 2014,one hundred and seventy-five H. pylori infected patients who had not been treated for H. pylori before wererandomized to receive either sequential therapy(rabeprazole 20 mg and amoxicillin 1 g twice daily for 5 d,followed by rabeprazole 20 mg,clarithromycin 500 mg and metronidazole 500 mg twice daily for 5 d) or hybrid therapy(rabeprazole 20 mg and amoxicillin 1 g for 7 d,followed by rabeprazole 20 mg,amoxicillin 1 g,clarithromycin 500 mg and metronidazole 500 mg twice daily for 7 d). H. pylori status was confirmed by positive results of both rapid urease test and histology examination or a positive result of culture. Eradication efficacy was assessed by follow-up endoscopy with rapid urease test and histological examination 8 wk after the end of anti-H. pylori therapy,or 13C-urea breath test at least 4 wk after completion of treatment. The primary outcome was H. pylori eradication by intension-to-treat(ITT) and per-protocol(PP) analyses.RESULTS: One hundred and sixty-seven patients(83 patients in the sequential group and 84 patients in the hybrid group) completed the study. The compliance rates were 97.6% and 97.7% for the two groups,respectively. The eradication rate was 78.2% for the sequential group and 92% for the hybrid group by ITT analysis(P = 0.01). The eradication rate was 81.9% for the sequential group and 96.4% for the hybrid group by PP analysis(P = 0.01). Univariate analysis for the clinical and bacterial factors did not identify any risk factors associated with treatment failure. Severe adverse events were observed in 2.3% of patients in the sequential group and 2.4% of those in the hybrid group.CONCLUSION: Due to a grade A(> 95%) success rate for H. pylori eradication by PP analysis,similar compliance and adverse events,hybrid therapy seems to be an appropriate eradication regimen in Taiwan.展开更多
AIM:To evaluate the efficacy of 14-d moxifloxacinbased sequential therapy as first-line eradication treatment of Helicobacter pylori(H.pylori) infection.METHODS:From December 2013 to August 2014, 161 patients with con...AIM:To evaluate the efficacy of 14-d moxifloxacinbased sequential therapy as first-line eradication treatment of Helicobacter pylori(H.pylori) infection.METHODS:From December 2013 to August 2014, 161 patients with confirmed H.pylori infection randomly received 14 d of moxifloxacin-based sequential group(MOX-ST group, n = 80) or clarithromycin-based sequential group(CLA-ST group, n = 81) therapy.H.pylori infection was defined on the basis of at least one of the following three tests:a positive 13C-urea breath test; histologic evidence of H.pylori by modified Giemsa staining; or a positive rapid urease test(CLOtest; Delta West, Bentley, Australia) by gastric mucosal biopsy.Successful eradication therapy for H.pylori infection was defined as a negative 13C-urea breath test four weeks after the end of eradication treatment.Compliance was defined as good when drug intake was at least 85%.H.pylori eradication rates, patient compliance with drug treatment, adverse event rates, and factors influencing the efficacy of eradication therapy were evaluated.RESULTS:The eradication rates by intention-to-treat analysis were 91.3%(73/80;95%CI:86.2%-95.4%)in the MOX-ST group and 71.6%(58/81;95%CI:65.8%-77.4%)in the CLA-ST group(P=0.014).The eradication rates by per-protocol analysis were 93.6%(73/78;95%CI:89.1%-98.1%)in the MOX-ST group and 75.3%(58/77;95%CI:69.4%-81.8%)in the CLAST group(P=0.022).Compliance was 100%in both groups.The adverse event rates were 12.8%(10/78)and 24.6%(19/77)in the MOX-ST and CLA-ST group,respectively(P=0.038).Most of the adverse events were mild-to-moderate in intensity;there was none serious enough to cause discontinuation of treatmentin either group.In multivariate analysis,advanced age(≥60 years)was a significant independent factor related to the eradication failure in the CLA-ST group(adjusted OR=2.13,95%CI:1.97-2.29,P=0.004),whereas there was no significance in the MOX-ST group.CONCLUSION:The 14-d moxifloxacin-based sequential therapy is effective.Moreover,it shows excellent patient compliance and safety compared to the 14-d clarithromycin-based sequential therapy.展开更多
AIM:To compare the effectiveness of sequential therapy for Helicobacter pylori(H.pylori) infection with that of triple therapy of varying durations.METHODS:The 460 patients enrolled in this study had H.pylori-associat...AIM:To compare the effectiveness of sequential therapy for Helicobacter pylori(H.pylori) infection with that of triple therapy of varying durations.METHODS:The 460 patients enrolled in this study had H.pylori-associated gastritis or a gastric or duodenal ulcer.After screening,H.pylori-infected patients were randomly assigned to receive either conventional triple therapy for 7,10 or 14 d,or a new 10-d sequential therapy.Each of the 4 treatment groups included 115 patients.The outcomes of eradication therapy were assessed 4 wk after treatment by the urea breath test and histology.RESULTS:The overall eradication rate was 81.0%,and eradication rates were 75.7% for 7-d conventional triple therapy,81.9% for 10-d conventional triple therapy,84.4% for 14-d conventional triple therapy,and 82.0% for 10-d sequential therapy.Neither intention-to-treat analysis nor per protocol analysis showed significant differences in eradication rates using sequential therapy or the standard triple therapy(P = 0.416 and P = 0.405,respectively).CONCLUSION:There are no significant differences between 10-d sequential eradication therapy for H.pylori and any duration of standard triple treatment in Korean patients.展开更多
OBJECTIVE:To evaluate the clinical efficacy of nourishing Yin and tonifying Yang sequential therapy(NYTYST)in combination with the Western Medicine Climen in treating diminished ovarian reserve(DOR).METHODS:From Septe...OBJECTIVE:To evaluate the clinical efficacy of nourishing Yin and tonifying Yang sequential therapy(NYTYST)in combination with the Western Medicine Climen in treating diminished ovarian reserve(DOR).METHODS:From September 2014 to September2016,46 patients with DOR who received NYTYST and Climen(treatment group)and 51 patients who received Climen only(control group)at the Jiangsu Provincial Traditional Chinese Medicine Hospital(Nanjing,China)were retrospectively reviewed.Before and at 3 months after treatment,serum levels of follicle-stimulating hormone(FSH),FSH/luteinizing hormone(LH),estradiol(E2),and anti-Mullerian hormone(AMH),the antral follicle count(AFC),stromal peak systolic velocity(PSV),symptom scores,and the clinical effectiveness rate were measured and compared between the two groups.RESULTS:After treatment,serum levels of FSH,FSH/LH and E2,and symptom scores were significantly decreased compared with before treatment(all P<0.05)in the two groups.AMH levels,AFC,and PSV were significantly increased after treatment compared with before treatment in both groups(all P<0.05).Serum levels of FSH,FSH/LH,and E2 after treatment were significantly lower in the treatment group than in the control group(all P<0.05).However,AMH levels and the AFC were significantly higher after treatment in the treatment group than in the control group(both P<0.05).The clinical effectiveness rate was significantly higher in the treatment group than in the control group(87%vs 68.6%,P<0.05).CONCLUSION:NYTYST combined with Climen may be more effective in treating DOR than Climen alone.展开更多
AIM:To evaluate the role of sequential therapy and Lactobacillus reuteri (L. reuteri ) supplementation, in the eradication treatment of Helicobacter pylori (H. pylori ). METHODS:H. pylori infection was diagnosed in 90...AIM:To evaluate the role of sequential therapy and Lactobacillus reuteri (L. reuteri ) supplementation, in the eradication treatment of Helicobacter pylori (H. pylori ). METHODS:H. pylori infection was diagnosed in 90 adult dyspeptic patients. Patients were excluded if previously treated for H. pylori infection or if they were taking a proton pump inhibitor (PPI), H2-receptor antagonist or antibiotics. Patients were assigned to receive one of the following therapies:(1) 7-d triple therapy (PPI plus clarithromycin and amoxicillin or metronidazole) plus L. reuteri supplementation dur- ing antibiotic treatment; (2) 7-d triple therapy plus L. reuteri supplementation after antibiotic treatment; (3) sequential regimen (5-d PPI plus amoxicillin therapy followed by a 5-d PPI, clarithromycin and tinidazole) plus L. reuteri supplementation during antibiotic treatment; and (4) sequential regimen plus L. reuteri supplementation after antibiotic treatment. Successful eradication therapy was defined as a negative urea breath test at least 4 wk following treatment. RESULTS:Ninety adult dyspeptic patients were en- rolled, and 83 (30 male, 53 female; mean age 57 ± 13 years) completed the study. Nineteen patients were administered a 7-d triple treatment:11 with L. reuteri supplementation during and 8 after therapy. Sixty-four patients were administered a sequential regimen:32 with L. reuteri supplementation during and 32 after therapy. The eradication rate was significantly higher in the sequential group compared with the 7-d triple regimen (88% vs 63%, P = 0.01). No difference was found between two types of PPI. No difference in erad- ication rates was observed between patients submitted to L. reuteri supplementation during or after antibiotic treatment. Compliance with therapy was excellent in all patients. No difference in adverse effects was observed between the different antibiotic treatments and between patients submitted to L. reuteri supplementation during and after antibiotic treatment. There was a low incidence of adverse effects in all groups of patients with sequential therapy, probably due to the presence of the L. reuteri supplementation. CONCLUSION:The sequential treatment regimen achieved a significantly higher eradication rate of H. pylori compared with standard 7-d regimen. L. reuteri supplementation could reduce the frequency and the intensity of antibiotic-associated side-effects.展开更多
BACKGROUND:This meta-analysis aimed to assess the efficacy of high-dose glucose-insulinpotassium(GIK) therapy on clinical outcomes in acute coronary syndrome(ACS) patients receiving reperfusion therapy.METHODS:We sear...BACKGROUND:This meta-analysis aimed to assess the efficacy of high-dose glucose-insulinpotassium(GIK) therapy on clinical outcomes in acute coronary syndrome(ACS) patients receiving reperfusion therapy.METHODS:We searched the PubMed,Web of Science,MEDLINE,Embase,and Cochrane Library databases from inception to April 26,2022,for randomized controlled trials(RCTs) that compared high-dose GIK and placebos in ACS patients receiving reperfusion therapy.The primary endpoint was major adverse cardiovascular events(MACEs).RESULTS:Eleven RCTs with 884 patients were ultimately included.Compared with placebos,high-dose GIK markedly reduced MACEs(risk ratio [RR] 0.57,95% confidence interval [95% CI]:0.35 to 0.94,P=0.03) and the risk of heart failure(RR 0.48,95% CI:0.25 to 0.95,P=0.04) and improved the left ventricular ejection fraction(LVEF)(mean difference [MD] 2.12,95% CI:0.40 to 3.92,P=0.02) at 6 months.However,no difference was observed in all-cause mortality at 30 d or 1 year.Additionally,high-dose GIK was significantly associated with increased incidences of phlebitis(RR 4.78,95% CI:1.36 to 16.76,P=0.01),hyperglycemia(RR 9.06,95% CI:1.74 to 47.29,P=0.009) and hypoglycemia(RR 6.50,95% CI:1.28 to 33.01,P=0.02) but not reinfarction,hyperkalemia or secondary reperfusion.In terms of oxidative stress-lowering function,high-dose GIK markedly reduced superoxide dismutase(SOD) activity but not glutathione peroxidase(GSH-Px) or catalase(CAT) activity.CONCLUSION:Patients with ACS receiving reperfusion therapy exhibited a reduction in MACEs and good oxidative stress-lowering eflcacy in response to high-dose GIK.Moreover,with a higher incidence of complications such as phlebitis,hyperglycemia,and hypoglycemia.Furthermore,there were no observed survival benefits associated with high-dose GIK.More trials with long-term follow-up are still needed.展开更多
Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin(PLD), a less cardiotoxic anthracycline, ...Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin(PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2(HER2)-positive early breast cancer(BC).Methods: In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD(30-35 mg/m^(2)) and cyclophosphamide(600 mg/m^(2)), followed by four cycles of taxanes(docetaxel,90-100 mg/m^(2) or nab-paclitaxel, 260 mg/m^(2)), concomitant with eight cycles of trastuzumab(8 mg/kg loading dose,then 6 mg/kg) and pertuzumab(840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response(tp CR, yp T0/is yp N0). Secondary endpoints included breast p CR(bp CR),objective response rate(ORR), disease control rate, rate of breast-conserving surgery(BCS), and safety(with a focus on cardiotoxicity).Results: Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42(53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval(95% CI), 48.5%-71.2%] patients achieved tp CR, and 49(62.8%) achieved bp CR. ORRs were 76.9%(95% CI, 66.0%-85.7%) and 93.6%(95% CI,85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine(11.5%) patients experienced asymptomatic left ventricular ejection fraction(LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP(NT-pro BNP), troponin I, or high-sensitivity troponin.Conclusions: This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety profile,especially a low risk of cardiac events, suggesting it as an attractive treatment approach with a favorable risk-benefit balance.展开更多
BACKGROUND A cure for Helicobacter pylori(H.pylori)remains a problem of global concern.The prevalence of antimicrobial resistance is widely rising and becoming a challenging issue worldwide.Optimizing sequential thera...BACKGROUND A cure for Helicobacter pylori(H.pylori)remains a problem of global concern.The prevalence of antimicrobial resistance is widely rising and becoming a challenging issue worldwide.Optimizing sequential therapy seems to be one of the most attractive strategies in terms of efficacy,tolerability and cost.The most common sequential therapy consists of a dual therapy[proton-pump inhibitors(PPIs)and amoxicillin]for the first period(5 to 7 d),followed by a triple therapy for the second period(PPI,clarithromycin and metronidazole).PPIs play a key role in maintaining a gastric pH at a level that allows an optimal efficacy of antibiotics,hence the idea of using new generation molecules.This open-label prospective study randomized 328 patients with confirmed H.pylori infection into three groups(1:1:1):The first group received quadruple therapy consisting of twice-daily(bid)omeprazole 20 mg,amoxicillin 1 g,clarith-romycin 500 mg and metronidazole 500 mg for 10 d(QT-10),the second group received a 14 d quadruple therapy following the same regimen(QT-14),and the third group received an optimized sequential therapy consisting of bid rabe-prazole 20 mg plus amoxicillin 1 g for 7 d,followed by bid rabeprazole 20 mg,clarithromycin 500 mg and metronidazole 500 mg for the next 7 d(OST-14).AEs were recorded throughout the study,and the H.pylori eradication rate was determined 4 to 6 wk after the end of treatment,using the 13C urea breath test.RESULTS In the intention-to-treat and per-protocol analysis,the eradication rate was higher in the OST-14 group compared to the QT-10 group:(93.5%,85.5%P=0.04)and(96.2%,89.5%P=0.03)respectively.However,there was no statist-ically significant difference in eradication rates between the OST-14 and QT-14 groups:(93.5%,91.8%P=0.34)and(96.2%,94.4%P=0.35),respectively.The overall incidence of AEs was significantly lower in the OST-14 group(P=0.01).Furthermore,OST-14 was the most cost-effective among the three groups.CONCLUSION The optimized 14-d sequential therapy is a safe and effective alternative.Its eradication rate is comparable to that of the 14-d concomitant therapy while causing fewer AEs and allowing a gain in terms of cost.展开更多
Background: Although Alzheimer’s disease (AD) has been intensively investigated for many years, the effective treatments are largely missing. Commonly used conventional therapy, such as cholinesterase inhibitors (ChE...Background: Although Alzheimer’s disease (AD) has been intensively investigated for many years, the effective treatments are largely missing. Commonly used conventional therapy, such as cholinesterase inhibitors (ChEI) and N-methyl D-asparate receptor antagonist, have been generally considered as having symptom-relieving rather than disease-modifying effects. Thus, how to improve cognitive function beyond such effect & time limitations has become a serious challenge. Aim: In order to solve this challenge, a sequential therapy with the integration of conventional therapy and herbal therapy was applied to AD patients. Careful clinical observation was conducted in our outpatient setting. Case Presentation: A case of probable AD received the sequential therapy has achieved relative stable cognition and overall status in eight years. Conclusion: During the treatment of this AD case in eight years, sequential therapy showed great potential in stabilizing and improving cognition and overall status. Well designed preclinical and clinical studies are needed to investigate the efficacy of sequential therapy for AD and other type of dementia.展开更多
Background: Increasing clarithromycin resistance has undermined the effectiveness of traditional clarithromycin-containing triple eradication therapy of Helicobacter pylori infections. Sequential and concomitant thera...Background: Increasing clarithromycin resistance has undermined the effectiveness of traditional clarithromycin-containing triple eradication therapy of Helicobacter pylori infections. Sequential and concomitant therapies show improved outcome with clarithromycin resistance. Aim: To evaluate the effectiveness of sequential and concomitant 4-drug non-bismuth therapies for eradication of Helicobacter pylori in a prospective, randomized, clinical trial conducted in Palestine. Patients and Methods: Patients who underwent upper endoscopy for a clinical indication and tested positive for rapid urease test were included. Subjects randomly allocated into two groups: One received a modified sequential therapy: esomeprazole 40 mg OD and amoxicillin 1 g BID for 5 days then esomeprazole 40 mg OD, clarithromycin 500 mg BID and tinidazole 500 mg BID for another 5 days. The other group received concomitant therapy in which the same 4 drugs and doses were all given daily for 10 days. Stool antigen was tested 4 weeks after completion of treatment. Results: Five hundred thirty three (533) patients were tested for H. pylori and 180 (34%) were positive;141 patients were included in the study and 112 patients completed. The overall per protocol eradication rate was (74%;95% CI = 65.9% - 82.1%). The eradication rates for sequential therapy was, (70.9%;95% CI = 58.9% - 82.9%) and for concomitant therapy (77.2%;95% CI = 66.3% - 88.1%). The results intention-to-treat were: sequential 61%, concomitant 57%. Conclusion: Neither sequential nor concomitant therapy achieved an acceptable H. pylori eradiation rate in Palestine.展开更多
BACKGROUND Perihilar cholangiocarcinoma(pCCA)is a highly malignant tumor arising from the biliary tree.Radical surgery is the only treatment offering a chance of long-term survival.However,limited by the tumor’s anat...BACKGROUND Perihilar cholangiocarcinoma(pCCA)is a highly malignant tumor arising from the biliary tree.Radical surgery is the only treatment offering a chance of long-term survival.However,limited by the tumor’s anatomic location and peri-vascular invasion,most patients lose the chance for curative treatment.Therefore,more methods to increase the resectability of tumors as well as to improve outcomes are needed.CASE SUMMARY A 68-year-old female patient had a hepatic hilar mass without obvious symptoms.Laboratory results showed hepatitis B positivity.Magnetic resonance imaging indicated that the mass(maximum diameter:41 mm)invaded the left and right branches of the main portal vein,as well as the middle,left and right hepatic veins;enlarged lymph nodes were also detected in the hilum.The patient was diagnosed with pCCA,and the clinical stage was determined to be T4N1M0(stage IIIC).Considering the tumor’s anatomic location and vascular invasion,systematic conversion therapy followed by ex vivo liver resection and autotrans-plantation(ELRA)was determined as personalized treatment for this patient.Our original systemic sequential therapeutic strategy(lenvatinib and tislelizumab in combination with gemcitabine and cisplatin)was successfully adopted as conversion therapy because she achieved partial response after three cycles of treatment,without severe toxicity.ELRA,anastomotic reconstruction of the middle hepatic vein,right hepatic vein,root of portal vein,inferior vena cava and right hepatic artery,and lymph node dissection were performed at one month after systemic therapy.Pathological and immunohistochemical examination confirmed the diagnosis of pCCA with lymph node metastasis.Although the middle hepatic vein was partially obstructed four months later,hepatic vein stent implantation successfully addressed this problem.The patient has survived for 22 mo after the diagnosis,with no evidence of recurrence or metastasis.CONCLUSION An effective therapeutic strategy for conversion therapy greatly increases the feasibility and efficiency of ELRA.展开更多
Vertical root fracture(VRF)in molars is a complex and frequently encountered dental condition.Successful management relies on accurate diagnosis,sequential treatment strategies,and systematic care.This paper provides ...Vertical root fracture(VRF)in molars is a complex and frequently encountered dental condition.Successful management relies on accurate diagnosis,sequential treatment strategies,and systematic care.This paper provides a comprehensive review of the sequential therapeutic approaches and systematic management models for molar VRF over the past five years.Particular attention is given to the diagnostic value of cone-beam computed tomography(CBCT),recent advances in tooth-preserving techniques,and the establishment of full-course management frameworks.By constructing an integrated pathway encompassing diagnostic assessment,treatment decision-making,clinical intervention,and long-term maintenance,a“dentist–nurse–patient community”model is proposed to promote standardized clinical guidance.This collaborative model aims to extend the lifespan of affected teeth and restore optimal masticatory function.展开更多
AIM： To analyze the reasons that may lead to the different vision result by combining the ranibizumab and triamcinolone acetate（TA） in sequence to treat macular edema in retinal vein occlusion（RVO）.METHODS： Rani...AIM： To analyze the reasons that may lead to the different vision result by combining the ranibizumab and triamcinolone acetate（TA） in sequence to treat macular edema in retinal vein occlusion（RVO）.METHODS： Ranibizumab and TA were combined in sequence to treat 43 patients with macular edema secondary to RVO.Six months after the treatment,patients with central fovea thickness（CFT） less than 300 μm in optical coherence tomography（OCT） were collected into Groups I and II,based on vision acuity（VA） better than 78 letters or less than 60 letters.The age,baseline VA,duration from onset to treatment,CFT at the baseline,sub-retinal fluid（SRF）,sub-foveal exudates and injection times of TA and ranibizumab were taken into comparison.RESULTS： The mean age of the subjects was 46.4y in Group I but 57.5y in Group II.The difference of age was significant between groups（P〈0.01）.The mean baseline VA was 51.4 letters in Group I and 43.9 letters in Group II（P〈0.05）.The baseline CFT were 670.9 μm in Group I with SRF in 54.3% patients and 678.1 μm in Group II with SRF in 52.9%（P〉0.05）.The mean number of injections of TA was 0.9 and the mean number of injections of ranibizumab was 2.3 in Group I but 1.7 and 2.9 respectively in Group II.The treatment times of ranibizumab had no difference between the 2 groups（P〉0.05） but the difference of TA injection times was significant（P〈0.05）.Subfoveal exudates at final stage happened in no subjects in Group I but in 45.83% subjects in Group II.CONCLUSION： This combined treatment is safer than TA injection and cheaper than ranibizumab injection alone.Younger patients and earlier treatment will help to get better vision outcome.Subfoveal exudates at the final stage have significant relationship with vision outcome.No relationship existed between the baseline CFT,SRF and the vision outcome.展开更多
AIM： To evaluate the daily high-dose induction therapy with interferon-α2b （IFN-α2b） in combination with ribavirin for the treatment of patients who failed with interferon monotherapy and had a relapse, based on ...AIM： To evaluate the daily high-dose induction therapy with interferon-α2b （IFN-α2b） in combination with ribavirin for the treatment of patients who failed with interferon monotherapy and had a relapse, based on the assumption that the viral burden would decline faster, thus increasing the likelihood of higher response rates in this difficult-totreat patient group. METHODS： Seventy patients were enrolled in this study. Treatment was started with 10 NU IFN-α2b daily for 3 wk, followed by IFN-α2b 5 NU/TIW in combination with ribavirin （1 000-1 200 mg/d） for 21 wk. In case of a negative HCV RNA PCR, treatment was continued until wk 48 （IFN-α2b 3MU/TIW＋1000-1200 mg ribavirin/daily）. RESULTS： The dose of IFN-α2b or ribavirin was reduced in 16% of patients because of hematologic side effects, and treatment was discontinued in 7% of patients. An early viral response （EVR） was achieved in 60% of patients. Fifty percent of all patients achieved an end-oftreatment response （EOT） and d0% obtained a sustained viral response （SVR）. Patients with no response had a significantly lower response rate than those with a former relapse （SVR 30% vs 53%; P=0.049）. Furthermore, lower response rates were observed in patients infected with genotype la/b than in patients with non-1-genotype （SVR 28% vs7d%; P=0.001）. As a significant predictive factor for a sustained response, a rapid initial decline of HCV RNA could be identified. No patient achieving a negative HCV-RNA PCR at wk 18 or later eventually eliminated the virus. CONCLUSION： Daily high-dose induction therapy with interferon-α2b is well tolerated and effective for the treatment of non-responders and relapsers, when interferon monotherapy fails. A fast decline of viral load during the first 12 wk is strongly associated with a sustained viral response.展开更多
基金Supported by the National Natural Science Foundation of China,No.82270594the National Natural Science Foundation for Youths of China,No.82103151+1 种基金the Outstanding Youth Foundation of Hunan Province,No.2022JJ20092the Wisdom Accumulation and Talent Cultivation Project of Third Xiangya Hospital of Central South University,No.YX202103.
文摘BACKGROUND Effective acid suppression significantly enhances the eradication rate of Helicobacter pylori(H.pylori).AIM To assess the efficacy and safety of high-dose dual therapy(HDDT)utilizing various highly potent antisecretory medications,thereby providing additional clinical guidance for H.pylori eradication.METHODS The study population comprised untreated H.pylori patients from three medical centers in central China.From February 10,2024 to March 31,2024,439 subjects were randomly allocated to either the esomeprazole-amoxicillin(EA)or esomeprazole-amoxicillin-clarithromycin-bismuth(B-quadruple)group.Subsequently,from April 1,2024 to May 10,2024,367 subjects were randomly assigned to either the vonoprazan-amoxicillin(VA)or vonoprazan-amoxicillin-clarithromycin(VAC)group.The study recorded treatment efficacy,adverse events,compliance,symptom alleviation,and associated costs.RESULTS EA-dual demonstrated non-inferiority to B-quadruple regimen in modified intention-to-treat(mITT)and perprotocol(PP)analyses(P<0.025).However,the eradication rate of EA was lower than that of the B-quadruple group[70.59%vs 83.49%,92.86%vs 98.38%,93.94%vs 98.38%,intention-to-treat(ITT),mITT,PP respectively,P<0.05].In ITT,mITT,and PP analyses,VA-dual was non-inferior to VAC treatment(84.15%vs 83.15%,96.25%vs 92.73%,96.75%vs 93.75%,P<0.025).No significant differences were observed in adverse events,compliance,and symptom relief between groups.VA exhibited the lowest cost.Antibiotic use within 2 years,poor compliance,and suburban residence were associated with reduced eradication efficacy(P<0.05).CONCLUSION The HDDT based on vonoprazan demonstrated non-inferiority to the VAC triple regimen,suggesting its potential as a recommended first-line treatment for H.pylori eradication.While B-quadruple therapy showed better eradication rate than EA therapy,the latter proved non-inferior in mITT and PP analyses.Notably,antibiotic use within the preceding two years,adherence to treatment protocols,and patient residence emerged as critical factors influencing eradication success.
文摘BACKGROUND Occult hepatitis B virus infection(OBI)is defined by the detection of replication-competent hepatitis B virus(HBV)DNA in the liver and/or blood despite the ab-sence of detectable hepatitis B surface antigen(HBsAg)using conventional ser-ological assays.Although OBI has been well-documented in individuals with resolved HBV infection or those receiving immunosuppressive therapy,reports of its occurrence during sequential antiviral treatment remain scarce.This report describes a case of chronic hepatitis B(CHB)transitioning through OBI during sequential combination therapy before ultimately achieving a functional cure.This case provides new insights into the emergence of OBI as a transitional phase during CHB treatment and emphasizes the importance of monitoring its clinical significance.CASE SUMMARY A 33-year-old Chinese male was diagnosed with HBV infection in 2001.The patient first presented in 2012 with abnormal liver function tests and received initial treatment with conventional interferon therapy,which failed to achieve a virological response.Antiviral therapy was subsequently switched to entecavir monotherapy.By August 2019,the patient exhibited an HBsAg level of 29.93 IU/mL with undetectable HBV DNA(<25 IU/mL).At this point,combination therapy with entecavir and pegylated interferonα(PEG-IFNα)was initiated.Remarkably,while HBsAg declined to 0.42 IU/mL by April 2020,a paradoxical HBV DNA rebound to 173 IU/mL was observed.The regimen was consequently modified to tenofovir alafenamide and PEG-IFNα.By October 2020,the patient achieved HBsAg seroconversion(HBsAg 0.01 IU/mL,hepatitis B surface antibody 52.18 mIU/mL)for the first time,while maintaining low-level viremia(37 IU/mL),consistent with transition to OBI.The patient was then switched to PEG-IFNαmonotherapy.In November 2021,he discontinued PEG-IFNαtherapy,and one month later,both HBV DNA(<10 IU/mL)and HBsAg(<0.05 IU/mL)were negative.This response has been sustained through follow-up.CONCLUSION This case study illustrates the efficacy of sequential combination therapy in achieving functional cure in CHB patients,including those with a prolonged infection history.It highlights OBI as a transitional yet underrecognized phase during sequential antiviral therapy.While the patient ultimately achieved functional cure,the transient persistence of HBV DNA despite HBsAg clearance suggests the need for continued monitoring.This case provides new insights into OBI development during treatment and underscores the importance of further research into its long-term implications.
文摘AIM: To compare the effectiveness of standard triple, bismuth pectin quadruple and sequential therapies for Helicobacter pylori (H. pylori ) eradication in a randomized, double-blinded, comparative clinical trial in China. METHODS: A total of 215 H. pylori -positive patients were enrolled in the study and randomly allocated into three groups: group A (n = 72) received a 10-d bismuth pectin quadruple therapy (20 mg rabeprazole bid , 1000 mg amoxicillin bid , 100 mg bismuth pectin qid , and 500 mg levofloxacin qd ); group B (n = 72) received the sequential therapy (20 mg omeprazole bid , 1000 mg amoxicillin bid , in 5 d, followed by 20 mg omeprazole bid , 500 mg tinidazole bid , 500 mg clarithromycin bid , for another 5 d); group C (n = 71) received a standard 1-wk triple therapy (20 mg omeprazole bid , 1000 mg amoxicillin bid , 500 mg clarithromycin bid ). After all these treatments, 20 mg omeprazole bid was administrated for 3 wk. H. pylori status was assessed by histology, 13C-urea breath test and rapid urease test at baseline and 4-6 wk after completion of treatment. Ulcer cicatrization was assessed by gastroscopy. χ 2 test (P < 0.05) was used to compare the eradication rates and ulcer cicatrisation rates among the three groups. RESULTS: The eradication rate was 83.33% (60/72) in group A, 88.89% (64/72) in group B, and 80.56% (58/71) in group C. The ulcer cicatrisation rate was 86.44% (51/59) in group A, 90.16% (55/61) in group B, and 84.91% (45/53) in group C. The sequential therapy yielded a higher eradication rate and ulcer cicatrisation rate than the standard triple and bismuth pectin quadruple therapies. Statistically, the eradication rate of group B was significantly different from groups A and C (P < 0.05), but the difference of ulcer cicatrisation rate and side effects was not statistically significant among the three groups (P > 0.05). The three protocols were generally well tolerated. CONCLUSION: The sequential therapy has achieved a significantly higher eradication rate, and is a more suitable first-line alternative protocol for anti-H. pylori infection compared with the standard triple and bismuth pectin quadruple therapies.
基金Supported by National Science and Technology Pillar Program of 12th Five-Year Plan in China,No.2012BAI06B02Clinical Key Projects of Peking University Third Hospital,No.Y76493-03Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal Diseases in Beijing,No.BZ0371
文摘AIM: To compare hybrid therapy(HT) with traditional sequential therapy(ST) and concomitant therapy(CT) for Helicobacter pylori(H. pylori) eradication.METHODS: We performed an electronic search of Pub Med, Embase, and the CENTRAL database. Randomized controlled trials(RCTs) of HT were included in the meta-analysis. The primary outcome was the eradication rate of H. pylori. The secondary outcomes included the compliance rate and adverse event rate. Effect estimates were pooled using the random-effects model.RESULTS: Twelve studies were included. Pooled results showed no significant differences in eradication rate between HT and ST in per-protocol(PP) analysis(RR = 1.03, 95%CI: 0.94-1.12, P = 0.59) or in intention-totreat(ITT) analysis(RR = 1.00, 95%CI: 0.89-1.12, P = 0.94). HT and ST showed similarly high compliance rate(96% vs 98%, P = 0.55) and acceptable adverse event rate(30.3% vs 28.2%, P = 0.63). No significant results were seen in the eradication rate between HT and CT in PP analysis(RR = 1.01, 95%CI: 0.96-1.05, P = 0.76) or in ITT analysis(RR = 0.99, 95%CI: 0.95-1.03, P = 0.47). HT displayed a slightly higher compliance rate than CT(95.8% vs 93.2%, P < 0.05). The adverse event rates of HT and CT were similar(39.5% vs 44.2%, P = 0.24).CONCLUSION: Compared with ST or CT, HT yields a similar eradication rate, high compliance rate, and acceptable safety profiles.
文摘Objective: Crizotinib is recommended as the first-line therapy for advanced anaplastic lymphoma kinase(ALK)-positive non-small-cell lung cancer(NSCLC). Despite its initial efficacy, patients ultimately acquire resistance to crizotinib within 1 year. In such patients, the optimal sequential therapy after crizotinib treatment remains unknown. This study explored which sequential therapy option confers the greatest benefit.Methods: A total of 138 patients with advanced ALK-positive NSCLC resistant to crizotinib were studied. Based on patterns of disease progression of metastases, patients were divided into 3 groups: brain progression, non-liver progression, and liver progression. Sequential therapies included crizotinib continuation plus local therapy, nextgeneration ALK inhibitors(ALKi's), and chemotherapy. The primary endpoint was overall survival(OS) from the time of crizotinib resistance to death or last follow-up.Results: The 138 patients included 64 cases with progression in brain, 57 cases in non-liver sites and 17 cases in liver. A significant difference in OS was observed among the distinct progression pattern(median OS, 25.4 months in brain, 15.8 months in non-liver, and 10.8 months in liver, respectively, P=0.020). The difference in OS among sequential therapies was statistically significant in the non-liver progression group(median OS, 27.6 months with next-generation ALKi's, 13.3 months with crizotinib continuation, and 10.8 months with chemotherapy,respectively, P=0.019). However, crizotinib continuation plus local therapy seems to provide non-inferior median OS compared with next-generation ALKi's for patients with brain progression(median OS, 28.9 months vs.32.8 months, P=0.204). And no significant differences in OS were found in patients with progression in liver(P=0.061).Conclusions: Crizotinib continuation together with local therapy might be a feasible strategy for patients with progression in brain beyond crizotinib resistance, as well as next-generation ALKi's. Next-generation ALKi's tended to provide a survival benefit in patients with non-liver progression.
文摘AIM: To evaluate the efficacy and safety of modified sequential therapy and to compare modified sequential therapy with standard quadruple therapy for Helicobacter pylori(H. pylori) eradication.METHODS: In total, 200 consecutive patients who were diagnosed with H. pylori-infected chronic gastritis by electronic endoscopy and rapid urease testing from December 2012 to October 2013 were enrolled in this study. The patients had not previously received H. pylori eradication treatment, and were randomized into two groups. The patients in Group A(n = 101) were treated with ilaprazole + bismuth potassium citrate + amoxicillin and clavulanate potassium + levofloxacin, and the patients in Group B(n = 99) were administered a modified sequential therapy composed of ilaprazole at 5 mg bid and amoxicillin and clavulanate potassium at 914 mg for the first five days followed by ilaprazole at 5 mg bid, furazolidone at 100 mg bid and levofloxacin at 500 mg qid for the next five days. Four to six weeks after the end of treatment, a 14C-urea breath test was performed for all the subjects to confirm the eradication of H. pylori. The intention-to-treat and per-protocol eradication rates were determined.RESULTS: A total of 190 of the 200 patients completed the study. All 200 patients were included in the intention-to-treat analysis, whereas 190 patients were included in the per-protocol analysis. In the intentionto-treat analysis, the rates of H. pylori eradication in Groups A and B were 85.15%(86/101) and 81.82%(81/99), respectively. In the per-protocol analysis, the H. pylori eradication rates in Groups A and B were 88.66%(86/97) and 87.09%(81/93), respectively. No significant difference was observed(χ2 = 0.109, P = 0.741) in the eradication rate between Groups A and B. The rates of adverse effects observed in the groups were similar at 6.19%(6/97) for Group A and 7.53%(7/93) for Group B(P > 0.05). No mortality or major morbidities were observed in any of the patients. Symptomatic improvements in the presentation of stomachache, acid regurgitation, and burning sensation were not significantly different between the two groups.CONCLUSION: Ilaprazole-based 10-d standard quadruple therapy does not offer an incremental benefit over modified sequential therapy for the treatment of H. pylori infection, as both treatment regimens appear to be effective, safe, and well-tolerated as initial treatment options.
文摘AIM: To evaluate the efficacy of sequential vs hybrid therapy in patients with Helicobacter pylori(H. pylori) infection.METHODS: From March 2013 to May 2014,one hundred and seventy-five H. pylori infected patients who had not been treated for H. pylori before wererandomized to receive either sequential therapy(rabeprazole 20 mg and amoxicillin 1 g twice daily for 5 d,followed by rabeprazole 20 mg,clarithromycin 500 mg and metronidazole 500 mg twice daily for 5 d) or hybrid therapy(rabeprazole 20 mg and amoxicillin 1 g for 7 d,followed by rabeprazole 20 mg,amoxicillin 1 g,clarithromycin 500 mg and metronidazole 500 mg twice daily for 7 d). H. pylori status was confirmed by positive results of both rapid urease test and histology examination or a positive result of culture. Eradication efficacy was assessed by follow-up endoscopy with rapid urease test and histological examination 8 wk after the end of anti-H. pylori therapy,or 13C-urea breath test at least 4 wk after completion of treatment. The primary outcome was H. pylori eradication by intension-to-treat(ITT) and per-protocol(PP) analyses.RESULTS: One hundred and sixty-seven patients(83 patients in the sequential group and 84 patients in the hybrid group) completed the study. The compliance rates were 97.6% and 97.7% for the two groups,respectively. The eradication rate was 78.2% for the sequential group and 92% for the hybrid group by ITT analysis(P = 0.01). The eradication rate was 81.9% for the sequential group and 96.4% for the hybrid group by PP analysis(P = 0.01). Univariate analysis for the clinical and bacterial factors did not identify any risk factors associated with treatment failure. Severe adverse events were observed in 2.3% of patients in the sequential group and 2.4% of those in the hybrid group.CONCLUSION: Due to a grade A(> 95%) success rate for H. pylori eradication by PP analysis,similar compliance and adverse events,hybrid therapy seems to be an appropriate eradication regimen in Taiwan.
文摘AIM:To evaluate the efficacy of 14-d moxifloxacinbased sequential therapy as first-line eradication treatment of Helicobacter pylori(H.pylori) infection.METHODS:From December 2013 to August 2014, 161 patients with confirmed H.pylori infection randomly received 14 d of moxifloxacin-based sequential group(MOX-ST group, n = 80) or clarithromycin-based sequential group(CLA-ST group, n = 81) therapy.H.pylori infection was defined on the basis of at least one of the following three tests:a positive 13C-urea breath test; histologic evidence of H.pylori by modified Giemsa staining; or a positive rapid urease test(CLOtest; Delta West, Bentley, Australia) by gastric mucosal biopsy.Successful eradication therapy for H.pylori infection was defined as a negative 13C-urea breath test four weeks after the end of eradication treatment.Compliance was defined as good when drug intake was at least 85%.H.pylori eradication rates, patient compliance with drug treatment, adverse event rates, and factors influencing the efficacy of eradication therapy were evaluated.RESULTS:The eradication rates by intention-to-treat analysis were 91.3%(73/80;95%CI:86.2%-95.4%)in the MOX-ST group and 71.6%(58/81;95%CI:65.8%-77.4%)in the CLA-ST group(P=0.014).The eradication rates by per-protocol analysis were 93.6%(73/78;95%CI:89.1%-98.1%)in the MOX-ST group and 75.3%(58/77;95%CI:69.4%-81.8%)in the CLAST group(P=0.022).Compliance was 100%in both groups.The adverse event rates were 12.8%(10/78)and 24.6%(19/77)in the MOX-ST and CLA-ST group,respectively(P=0.038).Most of the adverse events were mild-to-moderate in intensity;there was none serious enough to cause discontinuation of treatmentin either group.In multivariate analysis,advanced age(≥60 years)was a significant independent factor related to the eradication failure in the CLA-ST group(adjusted OR=2.13,95%CI:1.97-2.29,P=0.004),whereas there was no significance in the MOX-ST group.CONCLUSION:The 14-d moxifloxacin-based sequential therapy is effective.Moreover,it shows excellent patient compliance and safety compared to the 14-d clarithromycin-based sequential therapy.
文摘AIM:To compare the effectiveness of sequential therapy for Helicobacter pylori(H.pylori) infection with that of triple therapy of varying durations.METHODS:The 460 patients enrolled in this study had H.pylori-associated gastritis or a gastric or duodenal ulcer.After screening,H.pylori-infected patients were randomly assigned to receive either conventional triple therapy for 7,10 or 14 d,or a new 10-d sequential therapy.Each of the 4 treatment groups included 115 patients.The outcomes of eradication therapy were assessed 4 wk after treatment by the urea breath test and histology.RESULTS:The overall eradication rate was 81.0%,and eradication rates were 75.7% for 7-d conventional triple therapy,81.9% for 10-d conventional triple therapy,84.4% for 14-d conventional triple therapy,and 82.0% for 10-d sequential therapy.Neither intention-to-treat analysis nor per protocol analysis showed significant differences in eradication rates using sequential therapy or the standard triple therapy(P = 0.416 and P = 0.405,respectively).CONCLUSION:There are no significant differences between 10-d sequential eradication therapy for H.pylori and any duration of standard triple treatment in Korean patients.
基金Supported by the Clinical Medical Science and Technology Special of Jiangsu Provincial Science and Technology Project(No.BL2013039).
文摘OBJECTIVE:To evaluate the clinical efficacy of nourishing Yin and tonifying Yang sequential therapy(NYTYST)in combination with the Western Medicine Climen in treating diminished ovarian reserve(DOR).METHODS:From September 2014 to September2016,46 patients with DOR who received NYTYST and Climen(treatment group)and 51 patients who received Climen only(control group)at the Jiangsu Provincial Traditional Chinese Medicine Hospital(Nanjing,China)were retrospectively reviewed.Before and at 3 months after treatment,serum levels of follicle-stimulating hormone(FSH),FSH/luteinizing hormone(LH),estradiol(E2),and anti-Mullerian hormone(AMH),the antral follicle count(AFC),stromal peak systolic velocity(PSV),symptom scores,and the clinical effectiveness rate were measured and compared between the two groups.RESULTS:After treatment,serum levels of FSH,FSH/LH and E2,and symptom scores were significantly decreased compared with before treatment(all P<0.05)in the two groups.AMH levels,AFC,and PSV were significantly increased after treatment compared with before treatment in both groups(all P<0.05).Serum levels of FSH,FSH/LH,and E2 after treatment were significantly lower in the treatment group than in the control group(all P<0.05).However,AMH levels and the AFC were significantly higher after treatment in the treatment group than in the control group(both P<0.05).The clinical effectiveness rate was significantly higher in the treatment group than in the control group(87%vs 68.6%,P<0.05).CONCLUSION:NYTYST combined with Climen may be more effective in treating DOR than Climen alone.
文摘AIM:To evaluate the role of sequential therapy and Lactobacillus reuteri (L. reuteri ) supplementation, in the eradication treatment of Helicobacter pylori (H. pylori ). METHODS:H. pylori infection was diagnosed in 90 adult dyspeptic patients. Patients were excluded if previously treated for H. pylori infection or if they were taking a proton pump inhibitor (PPI), H2-receptor antagonist or antibiotics. Patients were assigned to receive one of the following therapies:(1) 7-d triple therapy (PPI plus clarithromycin and amoxicillin or metronidazole) plus L. reuteri supplementation dur- ing antibiotic treatment; (2) 7-d triple therapy plus L. reuteri supplementation after antibiotic treatment; (3) sequential regimen (5-d PPI plus amoxicillin therapy followed by a 5-d PPI, clarithromycin and tinidazole) plus L. reuteri supplementation during antibiotic treatment; and (4) sequential regimen plus L. reuteri supplementation after antibiotic treatment. Successful eradication therapy was defined as a negative urea breath test at least 4 wk following treatment. RESULTS:Ninety adult dyspeptic patients were en- rolled, and 83 (30 male, 53 female; mean age 57 ± 13 years) completed the study. Nineteen patients were administered a 7-d triple treatment:11 with L. reuteri supplementation during and 8 after therapy. Sixty-four patients were administered a sequential regimen:32 with L. reuteri supplementation during and 32 after therapy. The eradication rate was significantly higher in the sequential group compared with the 7-d triple regimen (88% vs 63%, P = 0.01). No difference was found between two types of PPI. No difference in erad- ication rates was observed between patients submitted to L. reuteri supplementation during or after antibiotic treatment. Compliance with therapy was excellent in all patients. No difference in adverse effects was observed between the different antibiotic treatments and between patients submitted to L. reuteri supplementation during and after antibiotic treatment. There was a low incidence of adverse effects in all groups of patients with sequential therapy, probably due to the presence of the L. reuteri supplementation. CONCLUSION:The sequential treatment regimen achieved a significantly higher eradication rate of H. pylori compared with standard 7-d regimen. L. reuteri supplementation could reduce the frequency and the intensity of antibiotic-associated side-effects.
基金supported by grants from the National Natural Science Foundation of China (82370378 and 82070388)Taishan Scholar Program of Shandong Province (tsqn202211310)National Natural Science Foundation of Shandong Province (ZR2020MH035)。
文摘BACKGROUND:This meta-analysis aimed to assess the efficacy of high-dose glucose-insulinpotassium(GIK) therapy on clinical outcomes in acute coronary syndrome(ACS) patients receiving reperfusion therapy.METHODS:We searched the PubMed,Web of Science,MEDLINE,Embase,and Cochrane Library databases from inception to April 26,2022,for randomized controlled trials(RCTs) that compared high-dose GIK and placebos in ACS patients receiving reperfusion therapy.The primary endpoint was major adverse cardiovascular events(MACEs).RESULTS:Eleven RCTs with 884 patients were ultimately included.Compared with placebos,high-dose GIK markedly reduced MACEs(risk ratio [RR] 0.57,95% confidence interval [95% CI]:0.35 to 0.94,P=0.03) and the risk of heart failure(RR 0.48,95% CI:0.25 to 0.95,P=0.04) and improved the left ventricular ejection fraction(LVEF)(mean difference [MD] 2.12,95% CI:0.40 to 3.92,P=0.02) at 6 months.However,no difference was observed in all-cause mortality at 30 d or 1 year.Additionally,high-dose GIK was significantly associated with increased incidences of phlebitis(RR 4.78,95% CI:1.36 to 16.76,P=0.01),hyperglycemia(RR 9.06,95% CI:1.74 to 47.29,P=0.009) and hypoglycemia(RR 6.50,95% CI:1.28 to 33.01,P=0.02) but not reinfarction,hyperkalemia or secondary reperfusion.In terms of oxidative stress-lowering function,high-dose GIK markedly reduced superoxide dismutase(SOD) activity but not glutathione peroxidase(GSH-Px) or catalase(CAT) activity.CONCLUSION:Patients with ACS receiving reperfusion therapy exhibited a reduction in MACEs and good oxidative stress-lowering eflcacy in response to high-dose GIK.Moreover,with a higher incidence of complications such as phlebitis,hyperglycemia,and hypoglycemia.Furthermore,there were no observed survival benefits associated with high-dose GIK.More trials with long-term follow-up are still needed.
基金supported by the National Natural Science Foundation of China (No. 82003311, No. 82061148016, No. 82230057 and No. 82272859)National Key R&D Program of China (No. 2022YFC2505101)+2 种基金Sun Yat-Sen Clinical Research Cultivating Program (No. SYS-Q202004)Beijing Medical Award Foundation (No. YXJL2020-0941-0760)Guangzhou Science and Technology Program (No. 202102010272 and No. 202201020486)。
文摘Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin(PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2(HER2)-positive early breast cancer(BC).Methods: In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD(30-35 mg/m^(2)) and cyclophosphamide(600 mg/m^(2)), followed by four cycles of taxanes(docetaxel,90-100 mg/m^(2) or nab-paclitaxel, 260 mg/m^(2)), concomitant with eight cycles of trastuzumab(8 mg/kg loading dose,then 6 mg/kg) and pertuzumab(840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response(tp CR, yp T0/is yp N0). Secondary endpoints included breast p CR(bp CR),objective response rate(ORR), disease control rate, rate of breast-conserving surgery(BCS), and safety(with a focus on cardiotoxicity).Results: Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42(53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval(95% CI), 48.5%-71.2%] patients achieved tp CR, and 49(62.8%) achieved bp CR. ORRs were 76.9%(95% CI, 66.0%-85.7%) and 93.6%(95% CI,85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine(11.5%) patients experienced asymptomatic left ventricular ejection fraction(LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP(NT-pro BNP), troponin I, or high-sensitivity troponin.Conclusions: This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety profile,especially a low risk of cardiac events, suggesting it as an attractive treatment approach with a favorable risk-benefit balance.
文摘BACKGROUND A cure for Helicobacter pylori(H.pylori)remains a problem of global concern.The prevalence of antimicrobial resistance is widely rising and becoming a challenging issue worldwide.Optimizing sequential therapy seems to be one of the most attractive strategies in terms of efficacy,tolerability and cost.The most common sequential therapy consists of a dual therapy[proton-pump inhibitors(PPIs)and amoxicillin]for the first period(5 to 7 d),followed by a triple therapy for the second period(PPI,clarithromycin and metronidazole).PPIs play a key role in maintaining a gastric pH at a level that allows an optimal efficacy of antibiotics,hence the idea of using new generation molecules.This open-label prospective study randomized 328 patients with confirmed H.pylori infection into three groups(1:1:1):The first group received quadruple therapy consisting of twice-daily(bid)omeprazole 20 mg,amoxicillin 1 g,clarith-romycin 500 mg and metronidazole 500 mg for 10 d(QT-10),the second group received a 14 d quadruple therapy following the same regimen(QT-14),and the third group received an optimized sequential therapy consisting of bid rabe-prazole 20 mg plus amoxicillin 1 g for 7 d,followed by bid rabeprazole 20 mg,clarithromycin 500 mg and metronidazole 500 mg for the next 7 d(OST-14).AEs were recorded throughout the study,and the H.pylori eradication rate was determined 4 to 6 wk after the end of treatment,using the 13C urea breath test.RESULTS In the intention-to-treat and per-protocol analysis,the eradication rate was higher in the OST-14 group compared to the QT-10 group:(93.5%,85.5%P=0.04)and(96.2%,89.5%P=0.03)respectively.However,there was no statist-ically significant difference in eradication rates between the OST-14 and QT-14 groups:(93.5%,91.8%P=0.34)and(96.2%,94.4%P=0.35),respectively.The overall incidence of AEs was significantly lower in the OST-14 group(P=0.01).Furthermore,OST-14 was the most cost-effective among the three groups.CONCLUSION The optimized 14-d sequential therapy is a safe and effective alternative.Its eradication rate is comparable to that of the 14-d concomitant therapy while causing fewer AEs and allowing a gain in terms of cost.
文摘Background: Although Alzheimer’s disease (AD) has been intensively investigated for many years, the effective treatments are largely missing. Commonly used conventional therapy, such as cholinesterase inhibitors (ChEI) and N-methyl D-asparate receptor antagonist, have been generally considered as having symptom-relieving rather than disease-modifying effects. Thus, how to improve cognitive function beyond such effect & time limitations has become a serious challenge. Aim: In order to solve this challenge, a sequential therapy with the integration of conventional therapy and herbal therapy was applied to AD patients. Careful clinical observation was conducted in our outpatient setting. Case Presentation: A case of probable AD received the sequential therapy has achieved relative stable cognition and overall status in eight years. Conclusion: During the treatment of this AD case in eight years, sequential therapy showed great potential in stabilizing and improving cognition and overall status. Well designed preclinical and clinical studies are needed to investigate the efficacy of sequential therapy for AD and other type of dementia.
文摘Background: Increasing clarithromycin resistance has undermined the effectiveness of traditional clarithromycin-containing triple eradication therapy of Helicobacter pylori infections. Sequential and concomitant therapies show improved outcome with clarithromycin resistance. Aim: To evaluate the effectiveness of sequential and concomitant 4-drug non-bismuth therapies for eradication of Helicobacter pylori in a prospective, randomized, clinical trial conducted in Palestine. Patients and Methods: Patients who underwent upper endoscopy for a clinical indication and tested positive for rapid urease test were included. Subjects randomly allocated into two groups: One received a modified sequential therapy: esomeprazole 40 mg OD and amoxicillin 1 g BID for 5 days then esomeprazole 40 mg OD, clarithromycin 500 mg BID and tinidazole 500 mg BID for another 5 days. The other group received concomitant therapy in which the same 4 drugs and doses were all given daily for 10 days. Stool antigen was tested 4 weeks after completion of treatment. Results: Five hundred thirty three (533) patients were tested for H. pylori and 180 (34%) were positive;141 patients were included in the study and 112 patients completed. The overall per protocol eradication rate was (74%;95% CI = 65.9% - 82.1%). The eradication rates for sequential therapy was, (70.9%;95% CI = 58.9% - 82.9%) and for concomitant therapy (77.2%;95% CI = 66.3% - 88.1%). The results intention-to-treat were: sequential 61%, concomitant 57%. Conclusion: Neither sequential nor concomitant therapy achieved an acceptable H. pylori eradiation rate in Palestine.
文摘BACKGROUND Perihilar cholangiocarcinoma(pCCA)is a highly malignant tumor arising from the biliary tree.Radical surgery is the only treatment offering a chance of long-term survival.However,limited by the tumor’s anatomic location and peri-vascular invasion,most patients lose the chance for curative treatment.Therefore,more methods to increase the resectability of tumors as well as to improve outcomes are needed.CASE SUMMARY A 68-year-old female patient had a hepatic hilar mass without obvious symptoms.Laboratory results showed hepatitis B positivity.Magnetic resonance imaging indicated that the mass(maximum diameter:41 mm)invaded the left and right branches of the main portal vein,as well as the middle,left and right hepatic veins;enlarged lymph nodes were also detected in the hilum.The patient was diagnosed with pCCA,and the clinical stage was determined to be T4N1M0(stage IIIC).Considering the tumor’s anatomic location and vascular invasion,systematic conversion therapy followed by ex vivo liver resection and autotrans-plantation(ELRA)was determined as personalized treatment for this patient.Our original systemic sequential therapeutic strategy(lenvatinib and tislelizumab in combination with gemcitabine and cisplatin)was successfully adopted as conversion therapy because she achieved partial response after three cycles of treatment,without severe toxicity.ELRA,anastomotic reconstruction of the middle hepatic vein,right hepatic vein,root of portal vein,inferior vena cava and right hepatic artery,and lymph node dissection were performed at one month after systemic therapy.Pathological and immunohistochemical examination confirmed the diagnosis of pCCA with lymph node metastasis.Although the middle hepatic vein was partially obstructed four months later,hepatic vein stent implantation successfully addressed this problem.The patient has survived for 22 mo after the diagnosis,with no evidence of recurrence or metastasis.CONCLUSION An effective therapeutic strategy for conversion therapy greatly increases the feasibility and efficiency of ELRA.
文摘Vertical root fracture(VRF)in molars is a complex and frequently encountered dental condition.Successful management relies on accurate diagnosis,sequential treatment strategies,and systematic care.This paper provides a comprehensive review of the sequential therapeutic approaches and systematic management models for molar VRF over the past five years.Particular attention is given to the diagnostic value of cone-beam computed tomography(CBCT),recent advances in tooth-preserving techniques,and the establishment of full-course management frameworks.By constructing an integrated pathway encompassing diagnostic assessment,treatment decision-making,clinical intervention,and long-term maintenance,a“dentist–nurse–patient community”model is proposed to promote standardized clinical guidance.This collaborative model aims to extend the lifespan of affected teeth and restore optimal masticatory function.
文摘AIM： To analyze the reasons that may lead to the different vision result by combining the ranibizumab and triamcinolone acetate（TA） in sequence to treat macular edema in retinal vein occlusion（RVO）.METHODS： Ranibizumab and TA were combined in sequence to treat 43 patients with macular edema secondary to RVO.Six months after the treatment,patients with central fovea thickness（CFT） less than 300 μm in optical coherence tomography（OCT） were collected into Groups I and II,based on vision acuity（VA） better than 78 letters or less than 60 letters.The age,baseline VA,duration from onset to treatment,CFT at the baseline,sub-retinal fluid（SRF）,sub-foveal exudates and injection times of TA and ranibizumab were taken into comparison.RESULTS： The mean age of the subjects was 46.4y in Group I but 57.5y in Group II.The difference of age was significant between groups（P〈0.01）.The mean baseline VA was 51.4 letters in Group I and 43.9 letters in Group II（P〈0.05）.The baseline CFT were 670.9 μm in Group I with SRF in 54.3% patients and 678.1 μm in Group II with SRF in 52.9%（P〉0.05）.The mean number of injections of TA was 0.9 and the mean number of injections of ranibizumab was 2.3 in Group I but 1.7 and 2.9 respectively in Group II.The treatment times of ranibizumab had no difference between the 2 groups（P〉0.05） but the difference of TA injection times was significant（P〈0.05）.Subfoveal exudates at final stage happened in no subjects in Group I but in 45.83% subjects in Group II.CONCLUSION： This combined treatment is safer than TA injection and cheaper than ranibizumab injection alone.Younger patients and earlier treatment will help to get better vision outcome.Subfoveal exudates at the final stage have significant relationship with vision outcome.No relationship existed between the baseline CFT,SRF and the vision outcome.
文摘AIM： To evaluate the daily high-dose induction therapy with interferon-α2b （IFN-α2b） in combination with ribavirin for the treatment of patients who failed with interferon monotherapy and had a relapse, based on the assumption that the viral burden would decline faster, thus increasing the likelihood of higher response rates in this difficult-totreat patient group. METHODS： Seventy patients were enrolled in this study. Treatment was started with 10 NU IFN-α2b daily for 3 wk, followed by IFN-α2b 5 NU/TIW in combination with ribavirin （1 000-1 200 mg/d） for 21 wk. In case of a negative HCV RNA PCR, treatment was continued until wk 48 （IFN-α2b 3MU/TIW＋1000-1200 mg ribavirin/daily）. RESULTS： The dose of IFN-α2b or ribavirin was reduced in 16% of patients because of hematologic side effects, and treatment was discontinued in 7% of patients. An early viral response （EVR） was achieved in 60% of patients. Fifty percent of all patients achieved an end-oftreatment response （EOT） and d0% obtained a sustained viral response （SVR）. Patients with no response had a significantly lower response rate than those with a former relapse （SVR 30% vs 53%; P=0.049）. Furthermore, lower response rates were observed in patients infected with genotype la/b than in patients with non-1-genotype （SVR 28% vs7d%; P=0.001）. As a significant predictive factor for a sustained response, a rapid initial decline of HCV RNA could be identified. No patient achieving a negative HCV-RNA PCR at wk 18 or later eventually eliminated the virus. CONCLUSION： Daily high-dose induction therapy with interferon-α2b is well tolerated and effective for the treatment of non-responders and relapsers, when interferon monotherapy fails. A fast decline of viral load during the first 12 wk is strongly associated with a sustained viral response.
