Network meta-analysis of pembrolizumab as monotherapy and in combination with chemotherapy for first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma / Metanálise em rede comparativa de pembrolizumabe como monoterapia e em combinação com quimioterapia para tratamento de primeira linha de carcinoma de células escamosas da cabeça e pescoço recorrente ou metastático

Pembrolizumab monotherapy or in combination with chemotherapy is approved as first-line treatment in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) based on improved overall survival (OS) versus EXTREME regimen in the KEYNOTE-048 trial. The clinical outcomes of pembrolizumab were compared with other recommended first-line treatments in R/M HNSCC in this study through a Bayesian network meta-analysis. A systematic literature review was conducted in July 2022, from which six trials that matched the KEYNOTE-048 patient eligibility criteria were included in the network. The OS and progression-free survival (PFS) outcomes were compared in the approved pembrolizumab indication (i.e., total population for pembrolizumab in combination with chemotherapy and combined positive score [CPS] ≥ 1 population for pembrolizumab monotherapy). A significant OS improvement was observed for pembrolizumab in combination with chemotherapy and pembrolizumab monotherapy versus EXTREME regimen (hazard ratio, 95% credible interval: 0.72, 0.60-0.86; 0.73, 0.60-0.88), platinum+5- FU (0.58, 0.43-0.76; 0.58, 0.44-0.78), and platinum+paclitaxel (0.53, 0.35-0.79; 0.53, 0.35-0.81), respectively. A non-significant numeric trend in OS improvement was observed versus the TPEx regimen. PFS was comparable with most first-line treatments and was improved versus platinum+5-FU (0.48, 0.36-0.64; 0.59, 0.45-0.79). Additional analyses in higher CPS subgroups also showed consistent results. Overall, our study results showed an improvement in OS outcomes versus alternative first-line treatments, consistent with the findings of the KEYNOTE-048 trial. These data support using pembrolizumab as a suitable firstline treatment option in R/M HNSCC.

Pembrolizumabe em monoterapia ou em combinação com quimioterapia é aprovado como tratamento de primeira linha em carcinoma de células escamosas recorrente/metastático de cabeça e pescoço (CECCP R/M) com base na melhora da sobrevida global (OS), em comparação com o esquema EXTREME no estudo KEYNOTE-048. Esse estudo comparou os resultados clínicos de pembrolizumabe com outros tratamentos recomendados de primeira linha em CECCP R/M por meio de uma metanálise de rede bayesiana. Uma revisão sistemática da literatura foi conduzida em julho de 2022, a partir da qual seis ensaios clínicos que atendiam aos critérios de elegibilidade de pacientes do KEYNOTE-048 foram incluídos na rede. Os desfechos de OS e sobrevida livre de progressão (PFS) foram comparados na indicação de pembrolizumabe (população total para pembrolizumabe em combinação com quimioterapia e população com escore positivo combinado [CPS] ≥ 1 em monoterapia com pembrolizumabe). Foi observada melhora significativa na OS para pembrolizumabe em combinação com quimioterapia e monoterapia com pembrolizumabe versus o esquema EXTREME (razão de risco, intervalo de confiança de 95%: 0,72, 0,60-0,86; 0,73, 0,60-0,88), platina+5-FU (0,58, 0,43-0,76; 0,58, 0,44-0,78) e platina+paclitaxel (0,53, 0,35-0,79; 0,53, 0,35-0,81), respectivamente. Uma tendência numérica não significativa de melhoria na OS foi observada em relação ao esquema TPEx. A PFS foi comparável com a maioria dos tratamentos de primeira linha e melhor em relação à platina+5-FU (0,48, 0,36-0,64; 0,59, 0,45-0,79). Análises adicionais em subgrupos com CPS mais elevado também mostraram resultados consistentes. No geral, os resultados de nosso estudo mostraram melhora nos desfechos de OS em comparação aos tratamentos de primeira linha alternativos, consistentes com os achados do estudo KEYNOTE-048. Esses dados apoiam o uso de pembrolizumabe como opção de tratamento em primeira linha em pacientes com CECCP R/M.

Meta-analysis of the Efficacy and Safety of High-dose Dual Therapy for the First-line Helicobacter pylori Infection / 医学研究杂志

Objective To systematically evaluate the efficacy and safety of high-dose dual therapy(HDDT)versus quadruple ther-apy(QT)for the first-line helicobacter pylori(Hp)infection.Methods The randomized controlled trial(RCT)about HDDT versus QT for the first-line treatment of Hp infection were searched from CNKI,VIP,Wanfang,CBM,PubMed,Embase,Cochrane Library and other databases from the establishment of databases to 3 July 2022.RevMan 5.4 and Stata 17.0software were used for Meta-analysis.Results A total of 1l studies with 4015 patients were included.The results of Meta-analysis showed that:the eradication rate of HDDT was statistically superior to that of QT(RR=1.04,95％CI:1.01-1.06,P＜0.01)in the intention-to-treat analysis;the eradica-tion rate of the two groups was not statistically significant(RR=1.02,95％CI:1.00-1.04,P=0.08)in the coincidence protocol a-nalysis.HDDT had a significantly lower rate of adverse reactions than QT(RR=0.47,95％CI:0.36-0.61,P＜0.01);but HDDT and QT both had achieved a similar eradication rate(RR=1.01,95％CI:1.00-1.02,P=0.06)in the per-protocol analysis.Conclusion The efficacy of HDDT in eradicating Hp infection for the first time is better than that of QT,and the safety is better,so it can be used as a first-line treatment in clinic.

The biotin synthesis pathway in Mycobacteria tuberculosis is a new target for the development of anti-tuberculosis drugs / 药学学报

italic>Mycobacterium tuberculosis, responsible for tuberculosis (TB), remains a major health problem worldwide and is one of the infectious diseases causing increased morbidity and mortality worldwide. Biotin, namely vitamin H, is an important cofactor necessary for fatty acid biosynthesis, gluconeogenesis and amino acid metabolism in organisms including Mycobacterium tuberculosis. Due to its inability to ingestion biotin from outside, Mycobacterium tuberculosis can only obtain biotin through biotin biosynthesis. Different from the classical BioC-BioH, BioI-BioW and non-classical BioZ pathways, Mycobacterium tuberculosis synthesized biotin by "BioC-BioH(2)" pathway in the early stage. This review focuses on the unique biotin synthesis pathway of Mycobacterium tuberculosis and its key genes, especially the response of this pathway and biotin-dependent carboxylase to tuberculosis first-and second-line drugs, as well as inhibitors and natural products targeting biotin synthesis.

Prevalence of depression in healthcare workers of a COVID-19 First Line Treatment Centre in North Kerala

Background: The COVID-19 pandemic had a widespread impact over the health-care system all over the world. This had resulted in varying degrees of psychological issues on healthcare workers. Aim and Objectives: The aim of the study was to assess the prevalence of depression among healthcare workers of a COVID-19 first line treatment center (CFLTC). Materials and methods: In this cross-sectional study, 240 healthcare workers who volunteered for the study at COVID first line treatment centre-3 NIT mega boys’ hostel, Kozhikode, Kerala were recruited. They were interviewed, basic demographic data and patient health questionnaire-9 was administered. The data were analyzed with Microsoft Excel. The prevalence among various categories of healthcare workers were compared. Results: The prevalence of depression among healthcare workers was 52%. The prevalence of depression is each category of staff-doctors, staff nurses, cleaning staffs, and patient caretakers-separately. It was found that depression is inversely proportional to the knowledge, experience, medical qualification, and training. Conclusion: The prevalence of undetected depression is high among healthcare workers working in unconventional environment as in warfront situations such as COVID pandemic. The present study emphasizes the importance of proper screening of depression among healthcare workers in such circumstances in years to come.

Drug resistance surveillance in Mycobacterium tuberculosis in Jiaxing City / 预防医学

Objective@#To investigate the resistance of Mycobacterium tuberculosis to first-line anti-tuberculosis drugs in Jiaxing City, Zhejiang Province from 2017 to 2019, so as to provide insights into improvements of the therapeutic effect of pulmonary tuberculosis. @*Methods@#Data pertaining to pulmonary tuberculosis in Jiaxing City from 2017 to 2019 were collected from the Tuberculosis Surveillance System of Chinese Disease Prevention and Control Information System, including demographics, treatment classification, sputum culture and drug resistance. The spectrum, types and prevalence of drug resistance in M. tuberculosis to four first-line tuberculosis drugs, including isoniazid (INH), rifampicin (RFP), streptomycin (SM) and ethambutol (EMB), was analyzed using a descriptive epidemiological method.@*Results@#A total of 1 310 M. tuberculosis isolates were cultured from pulmonary tuberculosis patients in Jiaxing City from 2017 to 2019, and there were 259 M. tuberculosis isolates that were resistant to anti-tuberculosis drugs, with an overall drug resistance rate of 19.77%. The prevalence rates of drug resistance to INH, SM, RFP and EMB were 13.36%, 11.83%, 5.50% and 3.59%, respectively. The prevalence of drug resistance was lower in M. tuberculosis isolates from treatment-naïve patients than from retreated patients (18.45% vs. 34.58%, P<0.05). M. tuberculosis isolates presented high resistance to SM (4.50%) and INH alone (4.35%), the highest resistance to INH-SM combinations (3.28%), and the highest resistance to INH+RFP+SM combinations (1.83%). Sixteen isolates were resistant to all the four drugs, with a drug resistance rate of 1.22%. The proportions of resistance to a single drug, RFP resistance, multidrug resistance and resistance to two and more drugs were 10.31%, 5.50%, 4.73% and 4.73%, respectively. In addition, the prevalence of RFP resistance among all patients and treatment-naïve patients both showed a tendency towards a rise from 2017 to 2019 (P<0.05). The prevalence of RFP resistance (7.01% vs. 3.76%) and resistance to two and more drugs (6.01% vs. 3.25%) was both higher among interprovincial mobile tuberculosis patients than among local non-mobile patients (P<0.05). @*Conclusions@#The overall prevalence of drug resistance was lower in M. tuberculosis isolates in Jiaxing City from 2017 to 2019 than in Zhejiang Province, with INH and RFP resistance as predominant types.

Pharmacoeconomic evaluation of serplulimab combined with chemotherapy regimens for the first-line treatment of extensive-stage small cell lung cancer / 中国药房

OBJECTIVE To evaluate the economics of serplulimab combined with chemotherapy regimens for the first-line treatment of extensive-stage small cell lung cancer （ES-SCLC） from the perspective of health system in China. METHODS A partitioned survival model was constructed based on the ASTRUM-005 clinical trial and related literature data， with a model simulation time frame of 10 years and a 3-week cycle， and both cost and utility values were discounted using a 5% discount rate. The quality-adjusted life year （QALY） was used as a model output indicator and the incremental cost-effectiveness ratio （ICER） was calculated to evaluate the economics of serplulimab combined with chemotherapy regimens （serplulimab group） versus chemotherapy alone regimens （chemotherapy alone group） for the first-line treatment of ES-SCLC. One-way sensitivity analysis and probabilistic sensitivity analysis were used to verify the robustness of the results of the base-case analysis and to conduct a scenario analysis for the serplulimab patient assistance program. RESULTS The results of the base-case analysis showed that compared with chemotherapy alone group， ICER of serplulimab group was 758 690.27 yuan/QALY， which was higher than 3 times China’s per capita gross domestic product （GDP） in 2022 as the willingness-to-pay （WTP） threshold. The results of the scenario analysis showed that compared with chemotherapy alone group， the ICER of serplulimab group was 172 275.74 yuan/QALY， which was below above WTP threshold. The one-way sensitivity analysis showed that the progress-free survival utility value， serplulimab price and so on had a significant impact on the model results. The results of the probabilistic sensitivity analysis showed that the probability of the serplulimab group being economic was 0 when the serplulimab patient assistance program was not considered， but 100% when the patient assistance program was considered. CONCLUSIONS At a WTP threshold of 3 times China’s per capita GDP in 2022， the serplulimab group is no cost-effectiveness compared to the chemotherapy alone group； however， this result is reversed when the patient assistance program is taken into account.

Analysis of the short-term efficacy of ustekinumab as the first-line treatment for Crohn′s disease / 中华消化杂志

Objective:To evaluate the short-term efficacy of ustekinumab (UST) as the first-line treatment of Crohn′s disease (CD).Methods:From October 1, 2020 to March 1, 2023, at the First Affiliated Hospital of Soochow University, 64 CD patients treated with UST as first-line biologics were enrolled. The patients were classified using the Montreal classification. Clinical and endoscopic response and remission were assessed by Crohn′s disease activity index (CDAI) and simple endoscopic score for crohn′s disease (SES-CD), respectively. Clinical response was defined as a reduction in CDAI score ≥70, and clinical remission was defined as a CDAI score <150; Endoscopic response was defined as ≥50% reduction from baseline in SES-CD score, and endoscopic remission was defined as SES-CD score ≤2. The clinical response rate and clinical remission rate at week 24 and week 48, as well as the endoscopic response rate and endoscopic remission rate at week 48 were observed in CD patients (only 21 patients with endoscopic prognostic results). Mann-Whitney rank sum test was used for statistical analysis.Results:Among 64 CD patients, there were 47 males and 17 females, with an age of (33.5±13.7) years old. According to Montreal classification, there were 3 cases (4.7%) of type A1 (≤16 years old), 44 cases (68.8%) of type A2 (17 to 40 years old), and 17 cases (26.6%) of type A3 (>40 years old); 43 cases (67.2%) of type L1 (terminal ileum type), 10 cases (15.6%) of type L2 (colonic type), 8 cases (12.5%) of type L3 (ileocolonic type), 1 case (1.6%) of type L4 (upper gastrointestinal type), 2 cases (3.1%) of type L1+ L4; 23 cases (35.9%) of type B1 (non-stricturing, non-penetrating), 34 cases (53.1%) of type B2 (stricturing), 2 cases (3.1%) of type B3 (penetrating), 5 cases (7.8%) of type B2+ B3; 44 cases (68.8%) complicated with perianal lesions. Among 56 CD patients with UST maintenance therapy once every 8 weeks, the CDAI scores at week 24 and 48 after treatment were both lower than that at week 0 (64.46(30.61, 123.30), 34.24(15.77, 64.83) vs. 353.40(290.40, 391.30)), and the CDAI score at week 48 after treatment was lower than that at week 24 after treatment, and the differences were statistically significant ( Z=-9.01, -9.13, and -3.14; P<0.001, <0.001, and =0.002). The clinical response rate was 100.0% (56/56) and the clinical remission rate was 91.1% (51/56) at week 24; the clinical response rate was 100.0% (56/56) and the clinical remission rate was 98.2% (55/56) at week 48. Among 39 CD patients complicated with perianal lesions, the closure rate of anal lesions at week 24 was 87.2% (34/39) and at week 48 was 100.0% (39/39). Among 8 CD patients who received UST maintenance therapy once every 12 weeks, the CDAI scores at week 24 and 48 were both lower than that at week 0 (100.40(71.20, 171.30), 38.49(18.25, 143.50) vs. 268.00(242.60, 364.90)), and the differences were statistically significant ( Z=-3.26 and -3.36; both P<0.001). At week 24, 7 CD patients achieved clinical response and 5 CD patients achieved clinical remission. At week 48, 8 CD patients achieved clinical response and 6 CD patients achieved clinical remission. Among 5 CD patients complicated with perianal lesions, 3 CD patients achieved perianal closure at week 24 and all 5 CD patients achieved closure of perianal lesions at week 48. Among 21 CD patients who underwent endoscopic evaluation, 16 CD patients received UST maintenance therapy once every 8 weeks, the SES-CD score at week 48 was lower than that at week 0 (4.00(3.00, 7.75) vs. 9.50(7.25, 10.75)), and the difference was statistically significant ( Z=-3.43, P<0.001), among them, 9 CD patients achieved endoscopic response and 2 CD patients achieved endoscopic remission; 5 CD patients received UST maintenance therapy once every 12 weeks, there was no statistically significant difference in the SES-CD score at week 48 compared with that at week 0 (4.00(1.50, 6.50) vs. 7.00(3.50, 10.00)) ( P>0.05), among them, 3 CD patients achieved endoscopic response and 1 CD patients achieved endoscopic remission. Conclusion:UST as the first-line treatment for CD patients can achieve clinical efficacy (response or remission), and the maintenance therapy is beneficial for endoscopic remission and closure of perianal lesions.

Effect of the area under the curve of carboplatin dosage on therapeutic efficacy and safety in Chinese patients with epithelial ovarian cancer / 西安交通大学学报(医学版)

【Objective】 To retrospectively analyze the average carboplatin dosage and calculate the area under the curve (AUC) using the Calvert formula in first-line chemotherapy in patients with epithelial ovarian cancer in The First Affiliated Hospital of Xi’an Jiaotong University so as to evaluate the effect of the AUC difference in the Chinese population on therapeutic efficacy and safety. 【Methods】 We enrolled patients who underwent first-line chemotherapy with paclitaxel and carboplatin 3-week regimen in our hospital from January 1, 2012 to January 1, 2022. According to the median of AUC, the patients were divided into high-dose group and low-dose group. The overall response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), and the incidence of adverse events (AEs) were compared. 【Results】 A total of 153 patients were enrolled in this study and the median AUC of carboplatin was 3.981 (range 2.314-5.446). Only 10.46% patients (16/153) had an AUC above 5. There were 77 patients with the AUC0.05). The ORR in the low-dose group and the high-dose group was 59.74% and 57.89%, respectively, and the DCR was 87.01% and 85.53%, respectively. The median PFS of the two groups was 14 and 15.5 months, respectively, and the median OS was 50 and 55 months, respectively. None of the above outcomes were statistically different between the two groups (P>0.05). The two groups showed significant differences in the incidence of anemia, neutropenia, and thrombocytopenia (P<0.05). The incidence of nausea and vomiting, grade 1-2 diarrhea or constipation, and grade 1-2 fever showed significant differences (P<0.05). In addition, the incidence of dose limiting toxicity (DLT), including grade 4 thrombocytopenia and febrile neutropenia (FN), was significantly increased in the high-dose group (P<0.05). 【Conclusion】 Compared with the recommended AUC 5-6 of carboplatin abroad, the actual carboplatin dosage in the first-line chemotherapy for patients with epithelial ovarian cancer was generally insufficient in our hospital. There was no difference in therapeutic efficacy between the patients with AUC<4 and AUC≥4. However, considering the increased risk of some AEs and DLT in the high-dose group, it is not recommended to increase the carboplatin AUC blindly.

Cost-utility analysis of pembrolizumab combined with chemotherapy in the first-line treatment of advanced or metastatic esophageal carcinoma / 中国药房

OBJECTIVE To evaluate the cost-utility of pembrolizumab combined with chemotherapy versus chemotherapy alone in the first-line treatment of advanced or metastatic esophageal carcinoma. METHODS Cost-utility analysis of pembrolizumab combined with chemotherapy versus chemotherapy alone for advanced or metastatic esophageal carcinoma was conducted by using a three-state partitioned survival model from the perspective of health system in China. The model use d a lifetime simulation time frame with 3 weeks as a cycle. The survival data were extrapolated using KEYNOTE- 590 data；cost data were obtained from the median of 2022 public winning bid on Yaozhi network ，among which the price of pembrolizumab was obtained after discounting by a patient assistance program ；utility data were obtained from the literatures ，and a 5％ discount rate was used for both cost and utility. One-way sensitivity analysis and probabilistic sensitivity analysis were also conducted to examine model robustness. RESULTS Analysis of the base case results showed that compared to chemotherapy alone ，the incremental cost-effectiveness ratio （ICER）of pembrolizumab combined with chemotherapy regimens were 950 528.42 yuan/QALY，107 845.39 yuan/QALY and 315 754.56 yuan/QALY for esophageal squamous cell carcinoma （ESCC），programmed deathligand- 1 combined positive score （PD-L1 CPS）≥10 and intention-to-treat population （ITT），respectively. The results of sensitivity analysis verified the robustness of the basic analysis results. CONCLUSIONS Under our healthcare system ，using a threshold of willingness-to-pay of 1-3 times our GDP per capita in 2021，pembrolizumab combined with chemotherapy regimen isn ’t cost-utility compared with chemotherapy alone in the ESCC and ITT subgroups of patients ，while it is cost-utility in the PD-L 1 CPS≥10 subgroup of patients.

Kinetics of MDSC in Patients Treated Steroids-Ruxolitinib as the First Line Therapy for aGVHD / 中国实验血液学杂志

OBJECTIVE@#To analyze the kinetic characteristics of lymphocyte subsets and myeloid-derived suppressor cell (MDSC) in patients who newly diagnosed intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy from a single-arm, open clinical trial (NCT04061876).@*METHODS@#We prospectively observed the efficacy of 23 patients having intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy. The kinetic characteristics of lymphocyte subsets and MDSC were monitored, and then we compared them in steroids-ruxolitinib group (n=23), free-aGVHD group (n=20) and steroids group (n=23).@*RESULTS@#Of the 23 patients, the CR rate was 78.26% (18/23) on day 28 after first-line treatment with steroids-ruxolitinib. On day 28 after treatment, patients had lower level of CD4+CD29+ T cells (P=0.08) than that of pre-treatment, whereas levels of other lymphocyte subsets in this study were higher than that of pre-treatment; CD4+CD29+ T cells in CR patients decreased, compared with refractory aGVHD patients. On day 28 of treatment, CD8+CD28- T cells (P=0.03) significantly increased in patients with aGVHD than that in patients without aGVHD, so did CD8+CD28- T / CD8+CD28+ T cell ratio (P=0.03). Compared with patients without aGVHD, patients with aGVHD had lower level of G-MDSC, especially on day 14 after allo-HSCT (P=0.04). Compared with pre-treatment, M-MDSC was higher in CR patients on day 3 and 7 post-treatment (P3=0.01, P7=0.03), e-MDSC was higher on day 28 post-treatment (P=0.01). Moreover, compared with CR patients, M-MDSC was lower in refractory aGVHD patients on day 3 post-treatment (P=0.01) and e-MDSC was lower on day 28 post-treatment (P=0.01). Compared with steroids group, MDSC in steroids-ruxolitinib group was higher, with the most significant difference in M-MDSC (P3=0.0351; P7=0.0142; P14=0.0369).@*CONCLUSION@#We found that patients newly diagnosed intermediate- to high-risk aGVHD receiving first-line therapy with steroids-ruxolitinib achieved high response rate. Moreover, the novel first-line therapy has a small impact on the immune reconstitution of patients after allo-HSCT. Elevated MDSC might predict a better response in aGVHD patients receiving this novel first-line therapy. M-MDSC responded earlier to steroids-ruxolitinib than e-MDSC, G-MDSC.

Economic Evaluation of Dexamethasone Combined with Rituximab for the First-line Treatment of Chronic Primary Immune Thrombocytopenia in Adults / 中国药房

OBJECTIVE：To evaluate the economy performance of dexamethasone （DXM）combined with rituximab （RTX） for the first-line treatment of chronic primary immune thrombocytopenia （ITP）in adults. METHODS ：From the perspective of China ’s medical and health system ，Markov model for eight states was constructed with a period of 4 weeks and a time limit of 20 years， using DXM regimen as control. The cost-utility of DXM+RTX regimen for the treatment of chronic ITP in adults were evaluated. The parameters of clinical efficacy and utility value were derived from own published literature ；cost parameters were from the MENET website and the official websites of local health committees and medical insurance bureaus ；one-way sensitivity analysis ， probability sensitivity analysis and scenario analysis were performed to observe the uncertainty of model and data source. RESULTS：The average cost of DXM+RTX regimen was 51 064 dollars and that of DXM regimen was 50 455 dollars. Compared with DXM regimen ，DXM+RTX regimen yielded an additional 0.14 QALYs for each patient ；the incremental cost-effectiveness ratio（ICER）was 4 356 dollars/QALY，and was lower than the willingness-to-pay threshold of China ’s per capita gross domestic product（GDP）in 2020. In the one-way sensitivity analysis ，the cost of drugs was the main driver in the model. Probability sensitivity analysis demonstrated that DXM+RTX regimen had 57.5％-61.0％ probability of being cost-effective at a willingness- to-pay threshold of 1-3 times per capita GDP in 2020. The results of scenario analysis showed that DXM+RTX regimen would have obvious long-term benefits ，and the utility value had little impact on the conclusion. CONCLUSIONS ：DXM + RTX is more economical than DXM in the treatment of chronic ITP in adults ，but the results have the uncertainty.

Rituximab as First-line Therapy for Severe Pemphigus: A Case Series and Review of Current Literature

Summary@#Pemphigus refers to a group of life-threatening, autoimmune blistering disease that presents as blisters and erosions involving the skin and mucosa. Systemic corticosteroids and rituximab have been recommended as mainstay therapy for pemphigus vulgaris and pemphigus foliaceus. Herein, we report three cases of pemphigus vulgaris and a case of pemphigus foliaceus treated with rituximab as first-line therapy.

First-line treatment of castration-resistant prostate cancer with enzaluamine / 中华泌尿外科杂志

This case was a 75-year-old prostate cancer patient with multiple cardiovascular diseases. The clinical stage was T 3bN 1M 0.After regular follow-up with androgen deprivation therapy (ADT)(Goserelin+ bicalutamide), the PSA increased slowly at the 13th month, and at the 17th month, the trend of progression to castrated resistant prostate cancer (CRPC) was considered, combined with patients with a variety of cardiovascular diseases, we choose the first-line application of Enzaluamine treatment, the disease has been effectively controlled. Through the diagnosis and treatment of this case, we should consider not only the effectiveness and safety of the treatment, but also the influence and risk of the treatment to the cardiovascular disease.

Therapeutic Effect of Apatinib in First-line Treatment of Advanced Liver Cancer / 肿瘤防治研究

Objective To explore the effect of apatinib in first-line treatment of advanced liver cancer. Methods Retrospective analysis was performed on 35 patients with advanced liver cancer treated in our department from July 2017 to January 2020. All patients were given apatinib mesylate tablet 250-500 mg orally with QD. The patients with effective disease control (including CR, PR and SD) were given administration until PD or intolerance or death occurred. The primary endpoints were PFS and OS, and the secondary endpoints were DCR and ORR. The side effect was observed. Results There was one case of CR, 17 cases of PR and 11 cases of SD. The ORR and DCR were 51.43% and 82.86%. The median PFS and OS were 9.7 and 11.1 months. The main adverse reactions included hand-foot syndrome, hypertension, proteinuria, etc. Most grade 3-5 adverse reactions were reversible with good safety. Conclusion Apatinib can significantly improve the clinical benefits of liver cancer patients. It is an alternative first-line treatment for advanced liver cancer.

Neutropenic Fever in Lung Cancer: Clinical Aspects Related to Mortality and Antibiotic Failure / 中国肺癌杂志

BACKGROUND@#Lung cancer (LC) is the leading cause of cancer death. Patients treated with chemotherapy are at risk of developing chemotherapy-induced febrile neutropenia (FN), a potentially life-threatening complication. The aims of this study were (1) to characterize FN admissions of patients with LC in a pulmonology department, and (2) to determine associations between patient profiles, first-line antibiotic failure (FLAF) and mortality.@*METHODS@#Retrospective observational case-series, based on the analysis of medical records of LC patients that required hospitalization due to chemotherapy-induced FN.@*RESULTS@#A total of 42 cases of FN were revised, corresponding to 36 patients, of which 86.1% were male, with a mean age of 66.71±9.83 years. Most patients had a performance status (PS) equal or less than 1, and metastatic disease was present in 40.5% (n=17). Respiratory tract infections accounted for 42.9% (n=18) of FN cases, and multidrug-resistant Staphylococcus aureus was the most isolated agent. The mortality rate was 16.7% (n=7), and the FLAF was 26.2% (n=11). Mortality was associated with a PS≥2 (P=0.011), infection by a Gram-negative agent (P=0.001) and severe anemia (P=0.048). FLAF was associated with longer hospitalizations (P=0.020), PS≥2 (P=0.049), respiratory infections (P=0.024), and infection by a Gram-negative (P=0.003) or multidrug-resistant agent (P=0.014).@*CONCLUSIONS@#Lower PS, severe anemia, and infections by Gram-negative or multi-resistant agents seem to be associated with worse outcomes in FN patients.

Research progression on the first-line biological target therapy of advanced / 中国肿瘤生物治疗杂志

@#With the progress of gene detection technology and the speed-up in new drug development, biological target therapy has fully covered the first-line treatment of advanced NSCLC. Immunotherapy has significantly improved the survival of advanced NSCLC patients with negative driven genes, and the median OS reaches about 2 years (15.6-30 months). EGFR is the most common driven gene. According to different EGFR mutation subtypes (L858R or 19del), different treatment mode (EGFR-TKI single drug, TKI combined with anti-vascular drugs and TKI combined with chemotherapy) is selected as the first-line treatment, which has become a consensus. Depending on the data of median PFS, the treatment efficacy against rare targets is more prominent, which has exceeded the efficacy of standard chemotherap:ALK (alectinib, PFS=34.8 months), ROS1 (ceritinib, PFS=19.3 months), RET (selpercatinib, PFS=18.4 months), BRAF (dabrafenib plus trametinib, PFS=14.6 months), NTRK (larotrectinib, PFS≥12 months) and MET (savolitinib, PFS=9.7 months). In conclusion, the first-line treatment of advanced NSCLC has entered the era of“precision-targeted treatment”based on different molecular typing, and it has become a consensus that high-throughput sequencing is required for newly diagnosed patients.

Comparative efficacy and safety of first-line EGFR-TKIs for advanced non-small cell lung cancer：a network meta-analysis / 中华疾病控制杂志

Objective To compare the efficacy and safety of gefitinib, erlotinib, and afatinib in the first-line treatment of advanced non-small cell lung cancer (NSCLC). Methods PubMed, EMBASE, and The Cochrane Library were searched to identify the relevant literatures published from December 2008 to December 2018. Bayesian network meta-analysis was carried out to rank the three treatments. Results A total of ten eligible studies involving 2275 patients were enrolled. In terms of efficacy, the surface under the cumulative ranking (SUCRA) indicated that erlotinib performed best in progression-free survival(PFS)(0.88), afatinib performed best in objective response rate(ORR)(0.82) and disease control rate(DCR) (0.86), gefitinib performed worst in PFS (0.45), ORR(0.42), and DCR(0.45). For safety, the differences of grade 3 or 4 adverse events rate (OR=0.29,95%CI:0.08-0.98) and discontinuation rate(OR=0.14,95%CI:0.01-0.8) between erlotinib and the platinum-based doublet chemotherapy were statistically significant. The ranking results also supported that erlotinib was the safest. SUCRA results suggested that gefitinib (0.31) had a lower grade 3 or 4 adverse events rate than afatinib (0.57), and the possibility of discontinuation in gefitinib (0.44) was similar to that of afatinib (0.41). Conclusion Erlotinib might be the preferred first-line treatment for advanced NSCLC after weighing and balancing the benefits and risks.

Patients experiences on the use of dihydroartemisinin piperaquine as an alternative first line artemisinin-based combination treatment for uncomplicated malaria in Northern Ghana

Background:Three different artemisinin-based combination therapies (ACTs) namely; artesunate-amodiaquine, artemether-lumefantrine and dihydroartemisinin-piperaquine (being the latest to be introduced) are concurrently being used forthe treatment of falciparummalaria in Ghana. This study assessed patients’ experience, perceptions and willingness to use dihydroartemisinin-piperaquine, brand name duo-cotecxin as an alternative first line ACT for the treatment of falciparummalaria in Northern Ghana.Methods:This was a qualitative study using phenomenology approach where sixty in-depth interviews were conducted with two groups; thirty patients who were given duo-cotecxin, one group and thirty interviews with patients who were given other ACTs (artesunate-amodiaquine, artemether-lumefantrine) as another group. The interviews were conducted between August and November, 2015 Purposive sampling technique was used to select study participants. The interviews were transcribed andcoded into themes using QSR NVivo 11 software for thematic content analysis.Results:All patients who used duo-cotecxin reported that the drug was very good in treating uncomplicated malaria compared to other ACTs they had used in the past. Some of the patients who used other ACTs could not complete their doses because of the side effects. However, none of the patients who used duo-cotecxin reported side effects. The findings revealed high acceptance and preference to use duo-cotecxin to treat uncomplicated malaria compared with other ACTs. All the participants were also willing to recommend duo-cotexcin to their relatives and friends to use. Conclusions: Duo-cotecxin as an alternative first line ACT for treatment of uncomplicated malaria is highly accepted, preferred and there was willingness to use it compared with other first line recommended ACTs.

Association between the HER2 Gene Status and the Efficacy of First-line Pemetrexed Combined with Platinum Chemotherapy in Patients with Advanced Lung Adenocarcinoma / 中国肺癌杂志

BACKGROUND@#Human epidermal growth factor receptor 2 (HER2) is one of the driver genes of non-small cell lung cancer (NSCLC). Several studies have shown that the efficacy of pemetrexed in HER2-mutant NSCLC is controversial. The aim of this study is to investigate the efficacy of pemetrexed combined with platinum chemotherapy in patients with HER2-mutant and HER2 wild-type lung adenocarcinoma.@*METHODS@#The clinical data of 106 cases of EGFR, ALK, ROS-1, KRAS, BRAF, RET and MET-negative patients with advanced lung adenocarcinoma patients who diagnosed by histopathology in the First Affiliated Hospital of Zhengzhou University were retrospectively reviewed. The relationships between HER2 gene status, clinical characteristics and response and progression-free survival (PFS) were analyzed.@*RESULTS@#All of the 106 patients' HER2 status were determined. HER2 mutations occurred in 32 cases (30.2%), no mutations in 74 cases (69.8%). HER2 mutations were common in young, non-smoking and female patients. All patients received first-line pemetrexed and platinum-based chemotherapy. The objective response rate (ORR) and disease control rate (DCR) of patients with HER2-mutant lung adenocarcinoma were significantly higher than those without HER2 mutations (40.6% vs 14.9%, χ²=8.464, P=0.004; 93.8% vs 68.9%, χ²=6.327, P=0.012), and the difference was statistically significant. According to univariate analysis, the PFS was significantly associated with the brain metastases, maintenance chemotherapy and HER2 gene status (P0.05). Cox multivariate analysis indicated that HER2 mutation was an independent positive prognostic factor of PFS (P=0.038).@*CONCLUSIONS@#HER2-mutant lung adenocarcinoma patients with first-line pemetrexed combined with platinum chemotherapy have greater clinical benefit than HER2 wild-type patients.

Efficacy and Safety of Afatinib for EGFR-mutant Non-small Cell Lung Cancer, Compared with Gefitinib or Erlotinib / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We tried to evaluate whether there are any specific features in treatment outcomes of firstline afatinib in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), compared with gefitinib or erlotinib. MATERIALS AND METHODS: We analyzed patients treated with first-line afatinib, gefitinib, or erlotinib for advanced EGFR-mutant NSCLC at Samsung Medical Center between 2014 and 2016. RESULTS: In total, 467 patients received first-line afatinib (n=165), gefitinib (n=230), or erlotinib (n=72). Afatinib was used more often in patients with tumors harboring deletion in exon 19 (Del19), whereas the gefitinib group had more elderly, females, and never smokers. The median progression-free survival (PFS) time for afatinib, gefitinib, and erlotinib was 19.1 months, 13.7 months, and 14.0 months, respectively (p=0.001). The superior PFS of afatinib was more remarkable in subgroups of Del19 or uncommon EGFR mutations. Overall toxicity profiles of the three drugs were comparable, though more grade 3 or 4 toxicities were detected in afatinib (7.3%) compared with gefitinib (2.6%) or erlotinib (1.8%). The common grade 3 or 4 toxicities of afatinib included diarrhea (3.0%), paronychia (2.4%), and skin rash (1.8%). Dose modification was more frequently required in patients treated with afatinib (112/165, 68%), compared with gefitinib (5/230, 2%) and erlotinib (4/72, 6%). Interestingly, however, dose reduction in the afatinib group did not impair its efficacy in terms of PFS (dose reduction vs. no reduction group, 23.5 months vs. 12.4 months). CONCLUSION: First-line afatinib showed satisfactory efficacy data and manageable toxicity profiles.