THE USE OF IONTOPHORESIS WITH HYALURONIC ACID ASSOCIATED WITH GOLD NANOPARTICLES ACCELERATES WOUND HEALING IN RATS

This study aimed to investigate the effects of iontophoresis with HA associated to GNPs solution in an epithelial lesion model. Fifty Wistar rats (n=10/group) were randomly assigned to the following groups: epithelial lesion (EL); (EL+MIC); (EL+MIC+HA); (EL+MIC+GNPs); (EL+MIC+HA-GNPs). The animals induced to an epithelial lesion and treatment started 24 hours after injury with microcurrents (300µA) containing gel with HA (0.9%) and/or GNPs (30mg/Kg) in the electrodes (1mL) for seven days. The animals were sacrificed 12 hours after the last treatment application. Results demonstrated a reduction in the levels of pro-inflammatory cytokines (IFNϒ, IL-1β, TNFα, IL6) in the group in which the therapies were combined; an increase in the levels of anti-inflammatory cytokines (IL-4, IL-10) and growth factors (FGF, TGFβ) in EL+MIC+HA and EL+MIC+HA-GNPs groups. As for dichlorofluorescein (DCF) and nitrite levels, decreased in the combined therapy group when compared to the control group, as well as the oxidative damage (carbonyl and sulfhydryl). In antioxidant defense, there was an increase in glutathione (GSH) and a decrease in superoxide dismutase (SOD) in the combination therapy group. Histological analysis showed a reduction in the inflammatory infiltrate in groups treated with MIC and in the combination therapy group. An increase in contraction of the wound area was obtained in all treated groups when compared to the control group, proving that the proposed therapies are effective in the process of epithelial healing. The results of this study demonstrated that the associated therapies favor the tissue repair process more significantly compared to the isolated therapies.

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Abstract 14134: Effects of Statin Plus Ezetimibe versus Statin Alone on Coronary Atherosclerosis in Acute Coronary Syndrome

Circulation ◽

10.1161/circ.132.suppl_3.14134 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Kiyoshi Hibi ◽

Kazuo Kimura ◽

Shinjo Sonoda ◽

Yutaka Otsuji ◽

Toyoaki Murohara ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Combination Therapy ◽

Therapy Group ◽

Combined Therapy ◽

Coronary Plaque ◽

Statin Treatment ◽

Combination Therapy Group ◽

Plaque Volume ◽

Coronary Syndrome ◽

Percent Change

Introduction: IMPROVE-IT trial showed that ezetimibe plus statin treatment, as compared with statin alone, decreased cardiovascular events in patients with acute coronary syndrome (ACS). However, proir studies have failed to show a beneficial effect of ezetimibe on carotid plaque progression when added to statin treatment. Hypothesis: The addition of ezetimibe to statin therapy affects coronary plaque behavior in the non-culprit vessel. Methods: We conducted a prospective, randomized open-label parallel group study with blind endpoint evaluation conducted at 10 centers in Japan. A total of 128 statin naïve patients with ACS undergoing intravascular ultrasound (IVUS) guided percutaneous coronary intervention were randomized and nonculprit coronary lesions associated with mild-to-moderate stenosis in 103 patients had evaluable IVUS examinations at baseline and at 8 to 12 months follow-up. Conventional IVUS and integrated backscatter (IB)-IVUS measurements at 1-mm intervals were calculated. Patients were randomly assigned to receive either 2mg/day of pitavastatin plus 10mg/day ezetimibe or 2mg/day of pitavastatin. Primary endpoints were the percentage change in non-culprit coronary plaque volume and percent change in lipid plaque volume. Results: Mean low density lipoprotein cholesterol was reduced from 125mg/dl to 65mg/dl in the combination therapy group receiving statin plus ezetimibe (n=50) and 126mg/dl to 87 mg/dl in the statin alone group (n=53)(between group difference of 16.9%, P<0.0001). Length of analyzed segment did not differ between the groups (median 38.0 vs. 41.2 mm, p=0.40). The primary endpoint, percent change in plaque volume, was -5.1% in the combination therapy group and -6.2% in the statin alone group (P=0.66), although both groups resulted in reduction of plaque volume compared with baseline (both p=0.001). The percent change in lipid plaque volume did not differ between the groups (4.3 vs. -3.0%, P=0.37). Conclusions: Among patients with acute coronary syndrome, combined therapy with ezetimibe and statin did not result in a significant change in coronary plaque regression or tissue component compared with statin alone.

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A combination of cognitive training and physical exercise for elderly with the mild cognitive impairment

Journal of Health Research ◽

10.1108/jhr-11-2018-0135 ◽

2019 ◽

Vol 33 (6) ◽

pp. 504-516 ◽

Cited By ~ 2

Author(s):

Ida Untari ◽

Achmad Arman Subijanto ◽

Dyah Kurnia Mirawati ◽

Ari Natalia Probandari ◽

Rossi Sanusi

Keyword(s):

Combination Therapy ◽

Physical Exercise ◽

Cognitive Training ◽

Therapy Group ◽

Meta Analysis ◽

Control Group ◽

Combination Therapy Group ◽

National Library ◽

Content Type ◽

Treatment Services

Purpose The purpose of this paper is to conduct systematic reviews on Indonesian papers, to examine the most recent evidence of the efficacy of the combination of cognitive training and physical exercise, and to make recommendations in order to improve prevention, care and treatment services in elderly patients with mild cognitive impairment (MCI). Design/methodology/approach The databases of Cochrane, Medline, NIH (US National Library Medicine), ProQuest, EbscoHost, Clinical Key, EMBASE, Medical Librarian (TWE) in Ovid, Science Direct, Scopus, The Lancet Global Health, PubMed, Emerald, Indonesian National Library, Google Scholar, Google Indonesia, and Garuda Portal were systematically searched using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to obtain empirical papers published between June 1976 and January 2018. Findings Out of the 3,293 articles collected, 10 were included in this analysis. The result of this combined meta-analysis compares the combination therapy group (cognitive therapy and physical exercise) with a control group. It shows that the control group was likely to experience MCI 1.65 times more often than the combination therapy group. According to the result acquired from the synthesized meta-analysis, the control group experienced MCI 1.65 times higher than the combination therapy. The finding is proven to be statistically significant (95% CI= 1.42–1.93). Research limitations/implications The research considers only English and Indonesian articles. Practical implications It is important to explore the most effective training characteristics in a special combined intervention differentiated by the duration, frequency, intervention, type and combination mode. There is a need for further investigation that focuses on the physiological mechanisms underlying the positive effects, by inserting a more comprehensive neuro-imaging measurement to assess specifically the domain that benefits in terms of cognitive functions and molecular markers. Finally, exploratory studies are definitely required, which will specifically examine maintenance and treatment effects as well as derive theoretical explanations related to the interventions and predictors. Social implications A combination of cognitive training and physical exercise intervention may improve the global health or cognitive functions. Originality/value A combination of cognitive training and physical exercise has been found to improve prevention, care and treatment services in elderly patients with MCI. There is an increase in value in comparison to the study of Karssemeijer, which considered five Indonesian articles.

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Effectiveness and Safety of Combination Therapy of Transarterial Chemoembolization and Apatinib for Unresectable Hepatocellular Carcinoma in the Chinese Population: A Meta-Analysis

Chemotherapy ◽

10.1159/000502510 ◽

2019 ◽

Vol 64 (2) ◽

pp. 94-104 ◽

Cited By ~ 1

Author(s):

Yan Wei ◽

Jianjun Liu ◽

Min Yan ◽

Shuguang Zhao ◽

Yong Long ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Combination Therapy ◽

Transarterial Chemoembolization ◽

Therapy Group ◽

Meta Analysis ◽

Cochrane Library ◽

Control Group ◽

Advanced Hepatocellular Carcinoma ◽

Combination Therapy Group ◽

Advanced Hcc

Background: The combination of transarterial chemoembolization (TACE) and apatinib has been used in the treatment of intermediate or advanced hepatocellular carcinoma (HCC). However, its effectiveness and safety are also argued. Methods: Eligible studies were collected from a computer search of literatures published from the database establishment to May 2019 in PubMed, Web of Science, EMBASE, Ovid, the Cochrane Library, Wanfang Database, China National Knowledge Infrastructure, and China Biology Medicine Disc. The objective response rate (ORR), the disease control rate (DCR), survival rate (SR), and the incidences of treatment-related adverse effects (AEs) were collected as the relevant outcomes. Data were analyzed through fixed/random effects of meta-analysis models with RevMan 5.3 software. Results: Eight randomized controlled clinical trials comprising 528 patients and 4 cohort studies comprising 226 patients were eventually included. Compared to the control group treated with TACE solely, combination therapy group, in which intermediate or advanced HCC patients were treated with TACE and apatinib, significantly enhanced ORR (relative risk [RR] 2.06, 95% CI 1.63–2.61, p < 0.001), DCR (RR 1.65, 95% CI 1.24–2.20, p < 0.001), and whole SRs of 6-month (RR 1.52, 95% CI 1.08–2.14, p = 0.02), 1-year (RR 1.52, 95% CI 1.25–1.84, p < 0.001), and 2-year (RR 1.84, 95% CI 1.34–2.54, p < 0.001). The incidence of hand foot syndrome, proteinuria, hypertension, and diarrhea was significantly increased in the combination therapy group compared with the control group (p < 0.05), and the incidence of nausea and vomiting, fever, and myelosuppression, respectively, was similar in 2 groups (p > 0.05). Conclusions: The combination therapy of TACE and apatinib can enhance the clinical effectiveness better than TACE solely in patients with intermediate or advanced HCC, while increase in the AEs is usually tolerable.

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The Comparison of Hypomethylating Agents (HMA) Monotherapy with HMA Combined with Intensive Chemotherapy for Intermediate / High-Risk MDS or AML

Blood ◽

10.1182/blood-2019-123335 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3903-3903

Author(s):

Jiang Ji ◽

Zhao Wang ◽

Bing Han

Keyword(s):

High Risk ◽

Combination Therapy ◽

Death Rate ◽

Therapy Group ◽

Meta Analysis ◽

Combination Group ◽

Combination Therapy Group ◽

Hypomethylating Agents ◽

Monotherapy Group ◽

Significant Difference

Introduction: Hypomethylating agents (HMA) azacitidine and decitabine were the first-line therapy for intermediate/ higher-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) patients unsuitable for hematopoietic cell transplantation (HSCT). HMA combined with chemotherapy was recently used to achieve for a better outcome. However, few studies were carried out to compare the HMA monotherapy to the HMA and chemotherapy combination therapy. This meta-analysis aimed to compare the efficacy, survival benefit and safety of HMA monotherapy and combination therapy (with chemotherapy) in patients with intermediate/high-risk MDS or AML. Methods: Related articles published between January 2009 and April 2019 were selected and patients were separated as monotherapy group and combination group for meta-analysis. To further eliminate the potential influence of differences in patients' baseline characteristic between the two groups, subgroups with similar patients' baseline characteristics were selected for further analysis. Complete response (CR) rate, overall response (ORR) rate, 1-year overall survival (OS) rate, 1-month death rate and the proportion of adverse event (AE) were pooled and compared. Results: 13 RCT or cohort studies with 997 patients (790 in monotherapy group, 207 in HMA combination group) were selected for meta-analysis. For the pooled data, there was no significant difference in sex and cytogenetic risk between the 2 groups, but the age of combination therapy group was significantly younger than that of the monotherapy group (61.3±13.2 year-old vs 67.7±10.2 year-old, p=0.000). The CR and ORR rate were significantly higher in combination therapy group (53% vs 17%, p=0.000 for CR and 67% vs 44%, p=0.000 for ORR). However, the 1-year OS (56% for combination therapy vs 51% for HMA monotherapy group, p=0.282) and 1-month death rate (5% for combination therapy vs 4% for HMA monotherapy group, p=0.965) were similar between the two groups. The incidence of CTCAE grade 3-4 infection and bleeding were significantly higher (infection: 50% for combination therapy vs 25.7% for monotherapy group, p=0.003; bleeding: 27.5%% for combination therapy vs 7.8% for monotherapy group, p=0.004) in combination group. In subgroup analysis, 117 and 179 patients were included in combination group and HMA monotherapy group, respectively. There was no significant difference in age (69.5±4.6 vs 69.0±6.8 years old, p=0.451) and proportion of favorable/intermediate cytogenetic risk (62% vs 71%, p=0.114) between the two groups, but a significantly lower proportion of male was found in combination therapy group (57% vs 74%, p=0.003). Although combination group had a higher CR rate (49% vs 17%, p=0.000), it had similar ORR rate (58% vs 49%, p=0.140) to monotherapy group. Meanwhile, combination therapy came with higher 1-month death rate (12% vs 3%, p=0.008) and lower 1-year OS (54% vs 68%, p=0.013) compared with monotherapy group. Conclusions: HMA combined with chemotherapy could increase CR rate in all patients and ORR rate in younger patients, but could not improve OS. For patients with similar older age, combination therapy could result in higher 1-month death rate and less 1-year OS. Disclosures No relevant conflicts of interest to declare.

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Anlotinib enhanced penpulimab efficacy through remodeling of tumor vascular architecture and immune microenvironment in hPD-L1/hPD-1 humanized mouse model.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.2581 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 2581-2581

Author(s):

Yunlong Shan ◽

Chongjin Zhong ◽

Qi Ni ◽

Mengying Zhang ◽

Guangji Wang ◽

...

Keyword(s):

Combination Therapy ◽

Mouse Model ◽

Immune Cells ◽

Immune Checkpoint ◽

Tumor Volume ◽

Combined Therapy ◽

Control Group ◽

Tyrosine Kinase Receptor ◽

Humanized Mouse ◽

Humanized Mouse Model

2581 Background: Even though immune checkpoint inhibitor (ICI) such as anti-PD-1 mAb has emerged as effective treatment for tumor regression, the response rate of ICI monotherapy in solid tumor is low. Many studies have demonstrated that the efficacy of combination therapy of ICI and anti-angiogenesis was superior to monotherapy. Penpulimab (AK105), a humanized IgG1 mAb that blocks PD-1 binding to PD-L1, engineered to eliminate FcγR binding and ADCC/ADCP completely. Here, we explore a new combined therapy of penpulimab and anlotinib, an oral multi-targeted tyrosine kinase receptor inhibitor. Methods: MC38-hPD-L1 tumor-bearing B-hPD-1 humanized mouse model were conducted to investigate the effects of anlotinib (1 mg/kg, every day, p.o) or penpulimab (5 mg/kg, twice a week, i.p) alone or in combination. Immunofluorescence was applied to elucidate tumor vessel normalization. In vivo imaging was conducted to detect the distribution of AF647-labelled penpulimab after anlotinib treatment. Flow cytometry and other techniques were performed to investigate intratumoral immune cells. Results: After 3-week treatment, immunotherapeutic administration of anlotinib or penpulimab showed moderate inhibition of tumor growth (tumor volume: 66.5% and 58.4% of control group, respectively), while combined treatment of anlotinib with penpulimab significantly decreased tumor volume to 36.5% of control group. Tissue pathological and blood biochemical results showed no significant toxic and side effects. Immunohistochemistry revealed that anlotinib induced tumor vascular normalization, indicated by decreased CD31+ area, increased α-SMA around tumor vessels and reduced GLUT1+ area. Furthermore, anlotinib markedly enhanced the delivery of AF647-penpulimab into tumors. Combining anlotinib with penpulimab also promoted infiltration and activity of anti-tumoral immune cells by reducing the level of immune checkpoint TIM3 and increasing the IFNγ secretion from T cells. Conclusions: Our work provides a strong scientific rationale for the combination therapy of anlotinib and penpulimab to improve tumor microenvironment and immunotherapy, which highlights the clinical potential for this new combined therapy.

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Effect of regional arterial infusion combined with early enteral nutrition on severe acute pancreatitis

Journal of International Medical Research ◽

10.1177/0300060519880760 ◽

2019 ◽

Vol 47 (12) ◽

pp. 6235-6243

Author(s):

Xiaojuan Wang ◽

Jinbu Xu ◽

Jiguang Li ◽

Yajuan Cheng ◽

Lu Liu ◽

...

Keyword(s):

Treatment Group ◽

Combination Therapy ◽

Conventional Treatment ◽

Therapy Group ◽

Early Enteral Nutrition ◽

Combination Therapy Group ◽

Arterial Infusion ◽

Conventional Treatment Group ◽

Effectiveness Rate ◽

Biochemical Indices

Objective To measure the therapeutic effects of regional arterial infusion (RAI) in combination with early enteral nutrition (EEN) in patients with severe acute pancreatitis (SAP). Methods A prospective randomized controlled study enrolled patients with SAP. They were randomly divided into a conventional treatment group that served as the control and a combination therapy group that received RAI combined with EEN. The Acute Physiology, Age, Chronic Health Evaluation II (APACHE II) scores, the levels of serum biochemical indices, functional recovery, the incidence of complications and total effectiveness rate were evaluated. Results A total of 100 patients were enrolled in the study. The APACHE II scores and the concentrations of blood glucose, serum amylase, white blood cell count, C-reactive protein, tumour necrosis factor-α, interleukin (IL)-6, IL-10 and IL-17 were significantly decreased, while albumin and serum calcium and total effectiveness rate in the combination therapy group were significantly higher than in the conventional treatment group. The combination therapy group had a significantly reduced time to abdominal pain relief, time of first defaecation, hospital stay and incidence of complications compared with the conventional treatment group. Conclusion The combination of RAI and EEN improved clinical biochemical indices, reduced the incidence of complications and promoted early recovery in patients with SAP.

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Efficacy and safety of PD-1/PD-L1 inhibitors plus nab-paclitaxel with or without bevacizumab as second-line therapy or beyond for patients with metastatic non-small-cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e20517 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e20517-e20517

Author(s):

Fan Zhang ◽

Tao Li ◽

Yuzi Zhang ◽

Shangli Cai ◽

Lei Zhao ◽

...

Keyword(s):

Combination Therapy ◽

Therapy Group ◽

Group Versus ◽

Combination Therapy Group ◽

Second Line ◽

Monotherapy Group ◽

Second Line Therapy ◽

Line Therapy ◽

Platinum Based Chemotherapy ◽

Nsclc Patients

e20517 Background: Immunotherapy combined with platinum-based chemotherapy is now standard first line treatment for NSCLC patients. However, limited evidence exists to show the efficacy of immunotherapy plus taxanes for patients who have progressed after platinum-based chemotherapy. Therefore, a retrospective study was conducted to assess whether immunotherapy plus nab-paclitaxel with or without bevacizumb could improve efficacy compared with immune monotherapy as second line therapy or beyond for NSCLC patients. Methods: Patients with metastatic NSCLC receiving anti-PD-1/PD-L1 monotherapy or combination therapy from 2015 to 2018 were identified in Chinese People’s Liberation Army General Hospital. Patients who received PD-1/PD-L1 inhibitors as first-line therapy or combined with therapies other than nab-paclitaxel and bevacizumab were excluded. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR) and safety. Results: Of 59 patients, 42 were treated with anti-PD-1/PD-L1 monotherapy and 17 were treated with anti-PD-1/PD-L1 plus nab-paclitaxel with or without bevacizumab. With a median follow-up of 8.2 months, combination therapy group showed significantly longer PFS compared with monotherapy group (8.4m vs. 3.7m, P = 0.047). When adjusted by covariates in COX proportional regression model, both treatment group (P = 0.007, Hazard ration [HR] 0.32; 95%CI 0.14-0.73) and performance status (P = 0.018, HR 0.44; 95%CI 0.22-0.87) demonstrated significant contribution to longer PFS. In addition, ORR was 23.5% (4/17) in the combination therapy group versus 12.8% (5/39) in the monotherapy group (P = 0.265) and the DCR was 88.2% (15/17) in the combination therapy group versus 61.5% (24/39) in the monotherapy group (P = 0.061). The incidence of grade 3/4 adverse events were 23.5% (4/17) in the combination therapy group and 4.8% (2/42) in monotherapy group (P = 0.052). Conclusions: PD-1/PD-L1 inhibitor plus nab-paclitaxel with or without bevacizumab resulted in significantly longer PFS and higher DCR as second line therapy of beyond in metastatic NSCLC patients. These findings need to be further explored by randomized controlled studies.

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Phenotypic and genetic characteristics of patients with type 2 diabetes with different responses to metformin therapy in Novosibirsk region

Diabetes Mellitus ◽

10.14341/dm2004146-47 ◽

2016 ◽

Vol 19 (2) ◽

pp. 125-131

Author(s):

Irina A. Bondar ◽

Olesya Y. Shabelnikova ◽

Ekaterina A. Sokolova ◽

Olga V. Pyankova ◽

Maksim L. Filipenko

Keyword(s):

Myocardial Infarction ◽

Combination Therapy ◽

Hba1c Level ◽

Therapy Group ◽

Combination Therapy Group ◽

Monotherapy Group ◽

Genetic Characteristics ◽

Novosibirsk Region ◽

Genotype C

Aim: The purpose of this study was to examine the phenotypic and genetic characteristics of patients with type 2 diabetes mellitus (T2DM) with different responses to treatment with metformin (MF) in the Novosibirsk region. Materials and methods: We examined 460 patients with T2DM in the Novosibirsk region. Patients were divided into groups according to their HbA1c level: patients who achieved the target HbA1c level during MF therapy (n = 209) and those who did not reach the target HbA1c level (n=251). Genotyping of ATM (rs11212617) was performed using polymerase chain reaction by TaqMan. Results: Patients who achieved the target HbA1c level during MF treatment (good response) were older (61. 1±9. 1 years vs. 57. 4±8. 4 years, p=0. 001), had later onset of diabetes (54. 6 ± 10. 1 years vs. 49. 2±8. 5 years, p = 0. 0001) and shorter duration of diabetes (6. 5±5. 9 years vs. 8. 2±6. 1 years, p=0. 03) compared with those who did not achieve the target HbA1c level. There was no statistically significant association between ATM rs11212617 and achieving the target HbA1c level among all patients [odds ratio (OR)=0. 94, 95% confidence interval = (0. 73–1. 23), p=0. 67] or those with MF monotherapy [OR=0. 90, (0. 65–1. 25), p=0. 54] or combination therapy [OR=1. 02, (0. 72–1. 43), p=0. 92]. There was an effect of age on response to MF therapy in all three groups (all patients: p=0. 001, MF monotherapy group: p=0. 04, combination therapy group: p=0. 0009). In the MF monotherapy group, low dose MF was associated with a good response (p=0. 03), and in the combination therapy group, males were more likely to have a good response (p=0. 003). Patients with genotype C/C or A/C for ATM (rs11212617) compared with those with genotype A/A were more likely to have high levels of triglycerides [2. 33 (1. 52–4. 2) mmol/l, 2. 09 (1. 35–3. 0) mmol/l and 1. 99 (1. 49–3. 21) mmol/l, respectively, p=0. 001], coronary heart disease (CHD) (13. 4%, 13. 4% and 9. 6%, respectively, p=0. 009) and myocardial infarction (7. 8%, 3. 2% and 4. 0%, respectively, p=0. 001). Conclusion: Patients with T2DM who had a good response to MF therapy were older, more likely to be male and had a later onset of T2DM. Genotype C/C for ATM rs11212617 was associated with high triglycerides, CHD and myocardial infarction. ATM rs11212617 was not associated with response to MF therapy in the Novosibirsk region.

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Efficacy of Different Nucleoside Analog Rescue Therapies for Entecavir-Resistant Chronic Hepatitis B Patients

10.21203/rs.3.rs-64765/v2 ◽

2020 ◽

Author(s):

Jin Shang ◽

Juan Zhou ◽

Huan Liu ◽

You Tu ◽

Jinqiu Ran ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis B ◽

Combination Therapy ◽

Chronic Hepatitis B ◽

Therapy Group ◽

Virologic Response ◽

Hbv Dna ◽

Combination Therapy Group ◽

Clinical Issue ◽

Significant Difference

Abstract Background Entecavir (ETV) is recommended as a first-line anti-HBV treatment. However, many chronic hepatitis B patients initiate anti-HBV treatment such as lamivudine and telbivudine with low genetic barriers in China, which leads to compensatory mutations and increases the rate of ETV resistance. The management of ETV resistance in China is an essential clinical issue. Methods Patients from 2011 to 2017 with nucleos(t)ide analog resistance were screened and 72 patients with ETV resistance were included. These patients received different rescue therapies including an ETV and adefovir (ADV) combination therapy group (n = 25), a tenofovir (TDF) monotherapy group (n = 27), and an ETV and TDF combination therapy group (n = 20). Virologic, biochemical, and serologic responses were compared among the three groups. Results The rate of ETV resistance increased form 6.04% in 2011 to 15.02% in 2017. Regarding the rates of negative HBV DNA at 48 weeks, no significant differences occurred in the TDF monotherapy and TDF combination groups (74.07% vs 70.00%), while the ETV and ADV group showed the worst virologic response (28.00%). TDF monotherapy and TDF combination therapy showed similar decline of HBV DNA at weeks 12, 24, and 48. There was no significant difference in the rates of HBeAg clearance, ALT normalization, and abnormal renal function between the three groups. Conclusions TDF monotherapy showed a comparable virologic response to TDF and ETV combination therapy and a better virologic response than ETV and ADV combination therapy. Thus, TDF monotherapy is the preferred rescue therapy for ETV resistance.

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IFN-α, IFN-γ, IL-2 combined with TNF-α for predicting efficacy of PD-1 inhibitors combination therapy in patients with solid cancers.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.2584 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 2584-2584

Author(s):

Penghui Xing ◽

Jinyan Zhang ◽

Rongfeng Liu ◽

Junyan Wang ◽

Ming Ma ◽

...

Keyword(s):

Combination Therapy ◽

Therapy Group ◽

Control Group ◽

Coincidence Rate ◽

Advanced Malignancies ◽

Tnf Α ◽

Significant Difference ◽

Group A ◽

Ifn Γ ◽

Group B

2584 Background: PD-1 inhibitors have transformed the treatment landscape for patients (pts) with many advanced malignancies. Combination therapy with PD-1 inhibitors for cancer is a trend. However, Biomarkers for the efficacy of combination therapy remains unknown. In order for the benefited population to be screened out, biomarkers need to be established. we will conduct the following study, to explore the IFN-α, IFN-γ, IL-2 combined with TNF-α for predicting efficacy of PD-1 inhibitors combination therapy. Methods: Using postoperative without lesions as control group (n=7). Pts with lesions as the experimental group (n=66). 27 of 66 pts received chemoradiotherapy (group A), 39 of 66 pts received PD-1 inhibitors combined with therapy (group B). IFN-α, IFN-γ, IL-2, TNF-α in peripheral blood of all pts were measured using flow cytometry. Results: 1) There was significant difference in proportion above normal concentrations (ANCs) of IFN-α between two groups (57.1% vs 43.5%, P<0.05), but there was no significant difference in IFN-γ, IL-2 and TNF-α between two groups (IFN-γ 57.1% vs 52.2%, IL-2 14.3% vs 5.8%, TNF-α 42.9% vs 43.5%, P>0.05). 2) The normal ratios of IFN-α, IFN-γ and TNF-α in group B was significantly higher than that in group A (IFN-α 64.1% vs 51.9%, IFN-γ 59% vs 37%, TNF-α 69.2% vs 44.4%, P<0.05). The proportion ANCs of IFN-α, IFN-γ, and TNF-α were lower in group A (IFN-α 35.9% vs 63%, P>0.05; IFN-γ 41% vs 63%, P<0.05; TNF-α 30.8% vs 55.6%, P<0.05). However, the proportion ANCs of IL-2 detection was lower (7.4% vs 5.1%). 3) In group B, 21 of 39 pts were evaluable. ORR was 52.4% (11/21) and DCR was 85.7% (18/21). The proportion ANCs of IFN-α, IFN-γ and TNF-α in the pts with PR was higher than that with SD (IFN-α 37.5% vs 28.6%, IFN-γ 37.5% vs 28.6%, TNF-α 50% vs 38.8%, P<0.05). 4) We found that the coincidence rate of IFN-α+ IFN-γ and IFN-α+ IFN-γ+TNF-α was higher in group B (Table). Conclusions: Our results suggest that the proportion ANCs of IFN-α, IFN-γ, and TNF-α in the pts with lesions were lower than that without lesions, it may be the decrease of immune function with lesions. There was positive correlation between proportion ANCs of IFN-α, IFN-γ and TNF-α and efficacy in these pts. IL-2 was not used as a routine detection indicator. The coincidence rate of IFN-α, IFN-γ combined with TNF-α was higher, it may help predict the outcome of PD-1 inhibitors combination therapy in pts with solid cancers, and helpful to screen the benefit population. Further study is needed.[Table: see text]

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