Safety and immunogenicity of a bivalent HPV16/18 vaccine in Chinese females.

As global supply is still inadequate to address the worldwide requirements for HPV vaccines, we assessed the safety and immunogenicity of a new bivalent HPV16/18 vaccine. In this randomized, double-blind, placebo-controlled, phase 2 trial, healthy 9-45-year-old Chinese females in three age cohorts (600 aged 9-17 years; 240 aged 18-26 years; 360 aged 27-45 years) were randomized 1:1 to receive three doses (0,2,6 months) of HPV16/18 vaccine or placebo. We measured neutralizing antibodies against HPV 16 and 18 at 7 months and monitored safety to 12 months in all age cohorts; 9-17-year-old girls were monitored for safety and immunogenicity to 48 months. In vaccinees, 99.8% seroconverted for HPV 16 and 18 types at 7 months; respective GMTs of 5827 (95% CI: 5249, 6468) and 4223 (3785, 4713) were significantly (p < .001) higher than controls for all comparisons. GMTs in the 9-17-year-olds, which were significantly higher than in older women at 7 months, gradually declined to 48 months but remained higher than placebo with seropositivity rates maintained at 98.5% and 97.6% against HPV 16 and 18, respectively. Adverse events occurred at similar rates after vaccine and placebo (69.8% vs. 72.5%, p = .308), including solicited local reactions and systemic adverse events which were mainly mild-to-moderate. The bivalent HPV16/18 vaccine was well tolerated and induced high levels of neutralizing antibodies in all age groups which persisted at high levels to 48 months in the 9-17-year-old age group which would be the target for HPV vaccination campaigns.

Safety and immunogenicity of a pichia pastoris-expressed bivalent human papillomavirus (types 16 and 18) L1 virus-like particle vaccine in healthy Chinese women aged 9-45 years: A randomized, double-blind, placebo-controlled phase 1 clinical trial.

BACKGROUND: We evaluated the safety and immunogenicity of high and low doses of a novel pichia pastoris-expressed bivalent (types 16 and 18) human papillomavirus (HPV) virus-like particle vaccine. METHODS: In this randomized, double-blind, placebo-controlled phase 1 trial, we enrolled 160 healthy females aged 9-45 years in Guangxi, China who were randomized (1:1:2) to receive either low (0.5 mL) or high (1.0 mL) dosages of bivalent HPV vaccine, or placebo (aluminum adjuvant) in a 0, 2, 6 months schedule. Adverse events and other significant conditions that occurred within 30 days after each vaccination were recorded throughout the trial. Sera were collected at days 0, 60, 180 and 210 to measure anti-HPV 16/18 neutralizing antibodies. RESULTS: A total of 160 participants received at least one dose of the HPV vaccine and 152 completed the three dose vaccination series. Reporting rates of adverse events in placebo, low dose (0.5 mL) and high dose (1.0 mL) groups were 47.5 %, 55.0 % and 55.0 %, respectively. No serious adverse events occurred during this trial. 100 % of the participants who received three doses of the HPV vaccine produced neutralizing antibodies against HPV 16/18 vaccine. For HPV 16 and HPV 18, the geometric mean titers (GMTs) were similar between the low dose group (GMTHPV 16 = 10816 [95 % CI: 7824-14953]), GMTHPV 18 = 3966 [95 % CI: 2693-5841]) and high dose group (GMT HPV 16 = 14482 [95 % CI: 10848-19333], GMT HPV 18 = 3428 [95 % CI: 2533-4639]). CONCLUSION: The pichia pastoris-expressed bivalent HPV vaccine was safe and immunogenic in Chinese females aged 9-45 years. The low dosage (0.5 mL) was selected for further immunogenicity and efficacy study.

Effectiveness of vero cell inactivated vaccine against severe acute respiratory infections (SARI) in Sibu, Malaysia: A retrospective test-negative design.

The effectiveness of the vero cell inactivated vaccine (CoronaVac®) against severe acute respiratory infection ( SARI) caused by SARS-CoV-2 in the real world was assessed. A matched test-negative case-control design was employed using the web-based national information system, as well as the hospitalization dataset in Sibu Hospital. Vaccine effectiveness was measured by conditional logistic regression with adjustment for gender, underlying comorbidity, smoking status, and education level. Between 15 March and 30 September 2021, 838 eligible SARI patients were identified from the hospitalization records. Vaccine effectiveness was 42.4% (95% confidence interval [CI]: -28.3 to 74.1) for partial vaccination (after receiving the first dose to 14 days after receiving the second dose), and 76.5% (95% CI: 45.6 to 89.8) for complete vaccination (at 15 days or more after receiving the second dose). This analysis indicated that two doses of CoronaVac® vaccine provided efficacious protection against SARI caused by SARS-CoV-2 in the short term. However, the duration of protection, and performance against new variants need to be studied continuously.

Hepatic Artery Injection of 131I-Metuximab Combined with Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Prospective Nonrandomized, Multicenter Clinical Trial.

This prospective nonrandomized, multicenter clinical trial was performed to investigate the efficacy and safety of 131I-labeled metuximab in adjuvant treatment of unresectable hepatocellular carcinoma. Methods: Patients were assigned to treatment with transcatheter arterial chemoembolization (TACE) combined with 131I-metuximab or TACE alone. The primary outcome was overall tumor recurrence. The secondary outcomes were safety and overall survival. Results: The median time to tumor recurrence was 6 mo in the TACE + 131I-metuximab group (n = 160) and 3 mo in the TACE group (n = 160) (hazard ratio, 0.55; 95% CI, 0.43-0.70; P < 0.001). The median overall survival was 28 mo in the TACE + 131I-metuximab group and 19 mo in the TACE group (hazard ratio, 0.62; 95% CI, 0.47-0.82; P = 0.001). Conclusion: TACE + 131I-metuximab showed a greater antirecurrence benefit, significantly improved the 5-y survival of patients with advanced hepatocellular carcinoma, and was well tolerated by patients.

Validation of the six-and-twelve criteria among patients with hepatocellular carcinoma and performance score 1 receiving transarterial chemoembolization.

BACKGROUND: Transarterial chemoembolization (TACE) is recommended for patients with intermediate hepatocellular carcinoma (HCC) according to treatment guidelines. However, a large number of patients with advanced HCC also receive TACE in clinical practice, especially for those with liver-confined HCC and Eastern Cooperative Oncology Group score (ECOG) 1. In view of previous studies, such patients have different prognoses from advanced HCC patients with macrovascular invasion or extrahepatic spread; therefore, patients with ECOG 1 alone might be classified into the intermediate stage and benefit from TACE treatment, but a study particularly focusing on such patients and exploring the effectiveness of TACE therapy is lacking. AIM: To investigate treatment outcomes of TACE in HCC patients with ECOG 1 alone and propose a specific prognostic model. METHODS: Patients from 24 Chinese tertiary hospitals were selected in this nationwide multicenter observational study from January 2010 to May 2016. Overall survival (OS) was estimated using Kaplan-Meier curves and compared by the log-rank test. Multivariate Cox regression was used to develop the potential prognostic models. The discriminatory ability of the models was compared and validated in various patient subgroups. The individual survival prediction for six-and-twelve (6&12) criteria, defined as the algebraic sum of tumor size (cm) and tumor number, was illustrated by contour plot of 3-year survival probability and nomogram. RESULTS: A total of 792 eligible patients were included. During follow-up, median OS reached 18.9 mo [95% confidence interval (CI): 16.9-21.0]. Three independent multivariate analyses demonstrated that tumor size, tumor number, α-fetoprotein level, albumin-bilirubin grade and total bilirubin were prognostic factors of OS (P < 0.05). The previously proposed 6&12 criteria was comparable or even better than currently proposed with the highest predictive ability. In addition, the 6&12 criteria was correlated with OS in various subgroups of patients. The patients were stratified into three strata with score ≤ 6, > 6 but ≤ 12, and > 12 with different median OS of 39.8 mo (95%CI: 23.9-55.7), 21.1 mo (95%CI: 18.4-23.8) and 9.8 mo (95%CI: 8.3-11.3), respectively (P < 0.001). CONCLUSION: TACE is effective for advanced HCC patients with ECOG 1 alone, and the 6&12 criteria may help with clinical decision-making.

Validation and evaluation of clinical prediction systems for first and repeated transarterial chemoembolization in unresectable hepatocellular carcinoma: A Chinese multicenter retrospective study.

BACKGROUND: The treatment outcome of transarterial chemoembolization (TACE) in unresectable hepatocellular carcinoma (HCC) varies greatly due to the clinical heterogeneity of the patients. Therefore, several prognostic systems have been proposed for risk stratification and candidate identification for first TACE and repeated TACE (re-TACE). AIM: To investigate the correlations between prognostic systems and radiological response, compare the predictive abilities, and integrate them in sequence for outcome prediction. METHODS: This nationwide multicenter retrospective cohort consisted of 1107 unresectable HCC patients in 15 Chinese tertiary hospitals from January 2010 to May 2016. The Hepatoma Arterial-embolization Prognostic (HAP) score system and its modified versions (mHAP, mHAP2 and mHAP3), as well as the six-and-twelve criteria were compared in terms of their correlations with radiological response and overall survival (OS) prediction for first TACE. The same analyses were conducted in 912 patients receiving re-TACE to evaluate the ART (assessment for re-treatment with TACE) and ABCR (alpha-fetoprotein, Barcelona Clinic Liver Cancer, Child-Pugh and Response) systems for post re-TACE survival (PRTS). RESULTS: All the prognostic systems were correlated with radiological response achieved by first TACE, and the six-and-twelve criteria exhibited the highest correlation (Spearman R = 0.39, P = 0.026) and consistency (Kappa = 0.14, P = 0.019), with optimal performance by area under the receiver operating characteristic curve of 0.71 [95% confidence interval (CI): 0.68-0.74]. With regard to the prediction of OS, the mHAP3 system identified patients with a favorable outcome with the highest concordance (C)-index of 0.60 (95%CI: 0.57-0.62) and the best area under the receiver operating characteristic curve at any time point during follow-up; whereas, PRTS was well-predicted by the ABCR system with a C-index of 0.61 (95%CI: 0.59-0.63), rather than ART. Finally, combining the mHAP3 and ABCR systems identified candidates suitable for TACE with an improved median PRTS of 36.6 mo, compared with non-candidates with a median PRTS of 20.0 mo (log-rank test P < 0.001). CONCLUSION: Radiological response to TACE is closely associated with tumor burden, but superior prognostic prediction could be achieved with the combination of mHAP3 and ABCR in patients with unresectable liver-confined HCC.

Sorafenib in combination with transarterial chemoembolization improves the survival of patients with unresectable hepatocellular carcinoma: a propensity score matching study.

OBJECTIVE: This prospective non-randomized controlled trial aimed to compare the efficacy of sorafenib in combination with transarterial chemoembolization (TACE) vs TACE alone for the treatment of patients with unresectable intermediate or advanced hepatocellular carcinoma. METHODS: A total of 304 patients were enrolled, in which 82 received concurrent sorafenib (400 mg orally twice daily, initiated within 14 days after TACE), and these patients were matched with 164 patients who received TACE alone at a 1:2 ratio using propensity score matching to minimize selection bias. The response to treatment, time-to-progression (TTP), overall survival (OS) as well as adverse events were compared between the two groups. RESULTS: During a median follow-up period of 21.4 weeks (range 0.5-103 weeks), the addition of sorafenib prolonged TTP (6.3 vs 4.3 months; hazard ratio [HR] 0.60, 95% CI 0.422-0.853, P = 0.004) and median survival (7.5 vs 5.1 months; HR 0.61, 95% CI 0.423-0.884, P = 0.009) compared with TACE alone. Significant prognostic factors for OS by multivariate analysis included the use of sorafenib, Barcelona Clinic Liver Cancer stage, metastasis/vascular invasion and Child-Pugh score. CONCLUSIONS: The combined use of sorafenib and TACE was generally well tolerated and significantly improved OS and TTP compared with TACE alone in patients with intermediate or advanced HCC. Further studies are warranted to confirm the safety and efficacy of this combination therapy.

Epidemiology and preventive direction of periodontology in China.

OBJECTIVE: The aim of this work was to estimate the present periodontal problems of people in China, based on an epidemiological investigation of adults. MATERIAL AND METHODS: The data were collected from the northwest, southwest, northeast and east regions (400 subjects from each region) of China. All subjects were over 25 years of age. About half of the subjects were farmers and about half were urban professionals. Everyone was asked to fill out a questionnaire and to undergo a professional oral examination. Periodontal health status was evaluated by a simplified oral hygiene index (OHI-S), gingival index (GI), bleeding on probing (BOP), probing pocket depth (PD), clinical attachment loss (CAL), and tooth mobility. RESULTS: Of the 1590 subjects enrolled in this investigation, 45.7% were male, 45.5% were farmers, and the remaining were urban professionals, and 27.7% of the subjects were smokers. There was a significant difference in the educational background but not smoking between the rural and urban groups. While 34.9% of the subjects in the urban group brushed only once per day, 56.1% of the subjects in the rural group did so. The prevalence of bleeding during brushing was 71.1%, while about 61.4% of the subjects know nothing about scaling. All periodontal indices were significantly higher in males than in females and higher in the rural group than in the urban group. PD, CAL and tooth mobility increased with age. The percentage of sites with CAL>3 mm in the rural group (49.5%) was significantly higher than that in the urban group (37.5%). Both current and former smokers showed increased CAL than non-smokers. CONCLUSION: Gingivitis and periodontitis are common findings in China. Most Chinese have no knowledge of common periodontal prevention and treatment and very few have regular dental care. The data of this study suggest that age, smoking, and limited education are significantly associated with Chinese adult periodontal attachment loss. Preventive periodontal care and education should be reinforced in the future by establishing relevant oral health projects.

Brain metastasis: experience of the Xi-Jing hospital.

BACKGROUND: The management of metastatic brain tumors is an important issue in patients with malignant tumors or cancer. The authors summarize the results of patients with brain metastases treated at the Xi-Jing Hospital during a 10-year period, in order to assess the best modality of treatment for patients with brain metastases. METHODS: Between 1990 and 2000, 463 patients with brain-metastatic tumors were treated at the Xi-Jing Hospital of the Fourth Military Medical University, Xian, China. In most patients, the pathologic diagnosis of primary cancer was obtained before they were referred for their brain metastasis. There were 34 (8.42%) cases with an unknown primary cancer site at the time of initial presentation. Patients were grouped according to treatment methods, which included neurosurgical craniotomy (NS; 130 patients), whole-brain radiotherapy (WBRT; 120 patients). Linac XKnife radiosurgery (RS; 130 patients) and Linac XKnife radiosurgery plus WBRT (RT; 83 cases). Survival was measured from the time of treatment and was analyzed by the Kaplan-Meier product-limit method and then plotted. Differences between curves were evaluated using the log-rank test. Multivariate factors associated with survival were analyzed using the Cox proportional hazards model. RESULTS: The survival time was 68.4 +/- 7.20 weeks after NS, 51.3 +/- 5.04 weeks after WBRT, 67.9 +/- 3.68 weeks after RS and 89.7 +/- 4.50 weeks after RT. The presence of active systemic cancer in a larger number of metastatic tumors was associated with a poor survival (p = 0.0003 and 0.0000). The female patients showed better survival rates over the male ones (p = 0.0000). Patients treated with RT had a better survival than those treated with NS, WBRT and RS (p = 0.0048, 0.0000 and 0.1222, respectively), although the latter did not show statistical significance. CONCLUSIONS: RS was an effective modality for patients with brain metastases, and if combined with WBRT, survival was better. Progression of systemic cancer and the number of metastatic tumors were the most significant factors for a poor survival after treatment of the brain metastases.