A comparative study of microbial changes in dental plaque before and after single- and multiappointment treatments in patients with severe early childhood caries.

BACKGROUND: The status of dental caries is closely related to changes in the oral microbiome. In this study, we compared the diversity and structure of the dental plaque microbiome in children with severe early childhood caries (S-ECC) before and after general anaesthesia and outpatient treatment. METHODS: Forty children aged 3 to 5 years with S-ECC who had completed whole-mouth dental treatment under general anaesthesia (C1) or in outpatient settings (C2) were selected, 20 in each group. The basic information and oral health status of the children were recorded, and the microbial community structure and diversity of dental plaque before treatment (C1, C2), the day after treatment(C2_0D), 7 days after treatment (C1_7D, C2_7D), 1 month after treatment (C1_1M, C2_1M), and 3 months after treatment (C1_3M, C2_3M) were analysed via 16 S rRNA high-throughput sequencing technology. RESULTS: (1) The alpha diversity test showed that the flora richness in the multiappointment group was significantly greater at posttreatment than at pretreatment (P < 0.05), and the remaining alpha diversity index did not significantly differ between the 2 groups (P > 0.05). The beta diversity analysis revealed that the flora structures of the C1_7D group and the C2_3M group were significantly different from those of the other time points within the respective groups (P < 0.05). (2) The core flora existed in both the pre- and posttreatment groups, and the proportion of their flora abundance could be altered depending on the caries status of the children in both groups. Leptotrichia abundance was significantly (P < 0.05) lower at 7 days posttreatment in both the single- and multiappointment groups. Corynebacterium and Corynebacterium_matruchotii were significantly more abundant in the C1_1M and C1_3M groups than in the C1 and C1_7D groups (P < 0.05). Streptococcus, Haemophilus and Haemophilus_parainfluenzae were significantly more abundant in the C1_7D group than in the other groups (P < 0.05). CONCLUSION: A single session of treatment under general anaesthesia can cause dramatic changes in the microbial community structure and composition within 7 days after treatment, whereas treatment over multiple appointments may cause slow changes in oral flora diversity.

Real-world study on HBsAg loss of combination therapy in HBeAg-negative chronic hepatitis B patients.

Combination therapy with pegylated interferon (PEG-IFN) and nucleos(t)ide analogues (NAs) can enhance hepatitis B surface antigen (HBsAg) clearance. However, the specific treatment strategy and the patients who would benefit the most are unclear. Therefore, we assessed the HBsAg loss rate of add-on PEG-IFN and explored the factors associated with HBsAg loss in chronic hepatitis B (CHB) patients. This was a real-world cohort study of adults with CHB. Hepatitis B e antigen (HBeAg)-negative NAs-treated patients with baseline HBsAg ≤1500 IU/ml and HBV DNA < the lower limit of detection, or 100 IU/ml, received 48 weeks of add-on PEG-IFN. The primary outcome of the study was the rate of HBsAg loss at 48 weeks of combination treatment. Using multivariable logistic regression analysis, we determined factors associated with HBsAg loss. HBsAg loss in 2579 patients (mean age: 41.2 years; 80.9% male) was 36.7% (947 patients) at 48 weeks. HBsAg loss was highest in patients from south-central and southwestern China (40.0%). Factors independently associated with HBsAg loss included: increasing age (odds ratio = 0.961); being male (0.543); baseline HBsAg level (0.216); HBsAg decrease at 12 weeks (between 0.5 and 1.0 log10 IU/ml [2.405] and >1.0 log10 IU/ml [7.370]); alanine aminotransferase (ALT) increase at 12 weeks (1.365); haemoglobin (HGB) decrease at 12 weeks (1.558). There was no difference in the primary outcomes associated with the combination regimen. In conclusion, HBsAg loss by combination therapy was higher in patients from southern China than those from the north. An increased chance of HBsAg loss was associated with baseline characteristics and dynamic changes in clinical indicators.

Increased interleukin 1α and interleukin 1ß expression is involved in the progression of periapical lesions in primary teeth.

BACKGROUND: Interleukin 1 (IL-1) is involved in bone resorption. However, the role of IL-1 in periapical lesions characterized by periapical bone destruction in primary teeth has not yet been fully elucidated. This study aimed to detect the distribution and expression of IL-1 in periapical lesions in primary teeth and assess the relationship between the cytokines and the degree of inflammatory cell infiltration. METHODS: A total of 106 chronic periapical lesions in primary teeth were harvested. Haematoxylin and eosin (H&E) staining was used to determine the histological type and the inflammatory cell infiltration grade (mild, moderate, and severe), and immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were used to detect the distribution and expression of IL-1α and IL-1ß. RESULTS: Of the 106 chronic periapical lesion samples, there were 85 cases of periapical granuloma, accounting for 80.19% of the total samples, and 21 cases of radicular cysts, accounting for 19.81%; no cases of abscess were detected. Immunohistochemistry results showed that both IL-1α and IL-1ß were expressed in periapical granulomas and cysts. ELISA results showed that IL-1α and IL-1ß levels were higher in the periapical granuloma group than in the radicular cyst and normal control groups (P < 0.05). In the periapical granuloma group, IL-1α and IL-1ß were detected at higher levels in the severe inflammatory cell infiltration subgroup than in the mild-inflammatory cell infiltration subgroup (P < 0.05), and IL-1ß expression was also higher in the moderate inflammatory cell infiltration subgroup than in the mild inflammatory cell infiltration subgroup (P < 0.01). A significant positive correlation was observed between the protein expression levels of IL-1α and IL-1ß and the inflammation grade in periapical granulomas from primary teeth (P < 0.05). CONCLUSION: Expression levels of the cytokines IL-1α and IL-1ß in periapical granulomas from primary teeth increased with increasing inflammatory severity and appeared to be a contributing factor to the progression of periapical lesions.

Nationwide survey of specialist knowledge on current standard of care (Peg-IFN/RBV) and barriers of care in chronic hepatitis C patients in China.

BACKGROUND AND AIM: Chronic hepatitis C virus (HCV) infection is the leading cause of liver diseases including cirrhosis and hepatocellular carcinoma. In China, it is a major national health problem that demands nationwide coordinated emphasis on prevention and treatment. To inform these initiatives, a nationwide survey was conducted from January to April 2015 to evaluate the knowledge, awareness, and perceived obstacles to HCV care. METHODS: A sample of 1000 HCV specialists across mainland China were recruited. Respondents were asked a series of 30 open-ended single or multiple response and Likert-scale questions about their HCV treatment knowledge, experience, assessment of HCV care status in China, and perceptions about treatment barriers. RESULTS: Sixty percent of the respondents answered incorrectly to more than half of the questions on basic HCV treatment principles. Over half of them incorrectly believed that maintenance therapy should be prescribed for non-responders (72%) and longer treatment duration improved sustained viral response rates (62%), regardless of HCV RNA level changes. Sixty-six percent of them believed that HCV treatment would still be interferon-based therapy in the next 5 years in China. Patient-related barriers, in particular lack of disease awareness, were considered to be the most significant barriers to HCV care. Payer and medical-provider barriers included affordability issues, lack of reimbursement coverage for testing and treatments, and lack of referral to HCV specialists. CONCLUSIONS: Focused and intense patient and provider education should be carried out to increase awareness. More effective direct-acting antivirals should be made available and affordable in China.

Simeprevir plus peginterferon/ribavirin for HCV genotype 1-infected treatment-naïve patients in China and South Korea.

BACKGROUND AND AIM: Approximately one-third of patients with hepatitis C virus (HCV) genotype (GT) 1 infection live in East Asia. This study evaluated the efficacy, pharmacokinetics, safety, and tolerability of simeprevir plus peginterferon alpha-2a and ribavirin (PR) in HCV GT1-infected, treatment-naïve, Asian patients with compensated liver disease. METHODS: This phase III, randomized study (NCT01725529) was conducted in China and South Korea. Patients received simeprevir 150 mg once daily (QD), simeprevir 100 mg QD, or placebo, in combination with PR for 12 weeks. Patients in the simeprevir groups received PR alone for a further 12 or 36 weeks based on response-guided treatment criteria. Patients in the placebo group received a further 36 weeks of PR alone. The primary efficacy endpoint was sustained virologic response 12 weeks after planned end of treatment (SVR12). Secondary endpoints were safety, pharmacokinetics, tolerability, and patient-reported outcomes. RESULTS: Overall, 457 patients were treated; the majority had GT1b infection (452/457 [99%]) and IL28B CC GT (364/457 [80%]). Of the 454 patients who had liver biopsy, 26 had cirrhosis (6%). SVR12 rates were superior for both the simeprevir 100 mg (89%; P = 0.003) and 150 mg (91%; P < 0.001) groups versus placebo (76%). Adverse events were mainly grade 1/2 and occurred at a similar incidence across all treatment groups. Overall, eight patients (2%) discontinued simeprevir or placebo treatment because of adverse events. CONCLUSIONS: Both simeprevir (100 mg and 150 mg QD) plus PR achieved superiority in SVR12 versus placebo plus PR in treatment-naïve, HCV GT1-infected, Asian patients and were well tolerated.

[The efficacy and prognostic predictors of different treatment courses with pegylated interferon α-2a and ribavirin combination in recurrent chronic hepatitis C patients].

OBJECTIVE: To study the efficacy and outcome predictors of combined re-treatment with pegylated interferon (Peg-IFN) α-2a and ribavirin in recurrent chronic hepatitis C (CHC) patients. METHODS: A multicenter, prospective, randomized trial was designed. A total of 125 recurrent CHC patients were recruited in 16 clinical centers and randomly assigned into two groups: one was Peg-IFNα-2a combined with ribavirin for 48 weeks (group A) and the other the same combination for 72 weeks (group B). HCV RNA levels in patients' serum were detected at baseline, week 4, 12, 24, 48, 72 (group B) after treatment initiation, and 24 weeks after treatment. RESULTS: Of all the 90 patients who completed treatment and 24 weeks follow-up, 80.0% achieved sustained virological response (SVR) yet 12.2% relapsed. There was no significant difference between two groups. The SVR rate in patients previously treated with interferon alone was higher than that in patients with interferon plus ribavirin (92.6% vs 74.6%), but the difference was of no statistical significance (P = 0.05). Moreover, patients previously treated with common interferon (c-IFN) showed a higher SVR rate than patients with Peg-IFN (84.7% vs 71.0%, P > 0.05). The positive predictive value (PV) of rapid virological response (RVR) and complete early virological response for SVR was 92.3% and 86.4% respectively, and the negative PV of RVR, early virological response and delayed virological response for SVR was 36.8%, 66.7% and 100.0% respectively. Overall, 62.1% patients reported adverse events (AEs) and 1.6% patients were severe AEs. CONCLUSIONS: A high SVR rate has been achieved in recurrent CHC patients who were retreated with Peg-IFNα-2a and ribavirin for 48 weeks. Better SVR cannot be achieved in spite of a prolonged course of 72 weeks. Early virological response at week 12 was the most important predictor for SVR.

Hepatitis C virus core antigen, an earlier and stronger predictor on sustained virological response in patients with genotype 1 HCV infection.

BACKGROUND: Earlier kinetics of serum HCV core antigen (HCVcAg) and its predictive value on sustained virological response (SVR) were investigated in patients with genotype 1 HCV infection during antiviral treatment. METHODS: In a multi-centered, randomized and positive drug-controlled phase IIb clinical trial on type Y peginterferon α-2b ( NCT01140997), forty-eight CHC patients who participated in pharmacokinetics were randomly divided into 4 cohorts and treated with PegIFNα (type Y peginterferon α-2b 90 µg, 135 µg, 180 µg and PegIFNα-2a 180 µg, respectively, once a week) and ribavirin (< 75 kg, 1000 mg daily and ≥ 75 kg, 1200 mg daily) for 48 weeks, and then followed up for 24 weeks. 32 patients infected with genotype 1 HCV and completed the whole process were included in this study. HCV RNAs were detected at baseline, and weeks 4, 12, 24, 48 and 72 using Cobas TaqMan. ARCHITECT HCVcAg was performed at 24, 48, 72, 96, 120 and 144 h in addition to the above time points. The receiver operating curves (ROCs) were performed to study the predictive values of HCVcAg decline on SVR. RESULTS: Following antiviral treatment, serum HCVcAg levels rapidly declined within the first week and correlated well with corresponding HCV RNA at baseline, weeks 4, 12, 24, 48 and 72 (rs = 0.969, 0.928, 0.999, 0.983, 0.985 and 0.946, respectively, P < 0.001). All of the areas under the receiver operating curves (AUROCs) were more than 0.80 and showed good predictive power on SVR at 24, 48, 72, 96, 120 and 144 h. The144 h was the best predictive time point of HCVcAg decline on SVR because of its largest AUROC (more than 0.90). CONCLUSIONS: Early kinetics of serum HCVcAg predicts SVR very well in genotype 1 CHC patients during antiviral treatment, and its reduction value at 144 h is an earlier and stronger predictor on SVR than rapid virological response and early virological response. (TRN: NCT01140997).

[Efficacy of standard antiviral therapy retreatment following interferon treatment failure in chronic hepatitis C patients].

OBJECTIVE: To investigate the therapeutic efficacy of standard antiviral therapy applied after interferon (IFN) treatment failure in patients with chronic hepatitis C (CHC). METHODS: CHC patients who completed a 48-week course of IFN therapy (pegylated (Peg)-IFNa-2a at 180 mug, qw, ih with or without ribavirin (RBV) at 15 mg/kg/w) in our hospital between January 2009 and June 2012 but who showed no response (at week 48) or who relapsed (at week 72) were enrolled in the study. Prior to initiating the 48-week course of retreatment therapy (Peg-IFNa-2a plus RBV as above), the hepatitis C virus (HCV) genotype was detected and the viral load measured (baseline) by PCR of HCV RNA. Each patient's response to therapy was classified as follows: baseline vs. week 4 (rapid virological response, RVR), vs. weeks 12 and 24 (early virological response, EVR), vs. week 48 (end of treatment virological response, ETVR) and vs. week 72 (sustained virological response, SVR). RESULTS: Of the total 235 cases administered retreatment therapy, 60.0% (n = 140) achieved RVR, 77.4% (n = 182) achieved EVR, 83.8% (n = 197) achieved ETVR, 68.0% (n = 68%) achieved SVR, and 15.7% (n = 37) relapsed. Stratification analysis of recurrence (n = 158) and non-responsive (n = 77) sub-groups showed that the recurrence group experienced significantly higher rates of RVR, EVR, ETVR and SVR, but a significantly lower rate of relapse. Stratification analysis of genotype 1b carrier (n = 206) and non-1b carrier (n = 29) sub-groups showed that the 1b carriers had significantly lower rates of RVR, EVR, ETVR and SVR, but a significantly higher rate of relapse. Finally, the patients who achieved RVR (vs. non RVR, n = 95) and EVR (vs. non-EVR, n = 53) showed higher rates of SVR and ETVR. CONCLUSION: CHC patients who fail to respond to the initial course of standard IFN-based therapy may achieve SVR upon retreatment, especially those infected with the HCV genotype 1b.

[Clinical features of antiviral therapy-induced thyroid disease in patients with chronic hepatitis C].

OBJECTIVE: To investigate the clinical features of thyroid disease occurring in response to antiviral therapy in patients with chronic hepatitis C (CHC). METHODS: Eighty-two patients diagnosed with CHC were recruited for study from our hospital between 2009 and 2010. All patients were given a 48-week course of antiviral combination therapy with pegylated-interferon (Peg-IFN; 180 mug qw ih) and ribavirin (RBV; 15 mg/kg bw). Patient sera was collected prior to treatment (baseline), at treatment weeks 24 and 48, and post-treatment week 24, and used to detect changes in levels of thyroid function markers, thyroid-specific and other autoantibodies, complement factors, and immunoglobulins (Igs). Differential expression of biomarkers was assessed between patients who developed thyroid disorder and those who did not. RESULTS: At treatment week 48, 13.4% (11/82) of cases developed hypothyroidism, 3.7% (3/82) developed hyperthyroidism, 20.7% (17/82) tested positive for thyroglobulin antibody, and 22.0% (18/82) tested positive for thyroid peroxidase antibody. The patients who did not develop thyroid disease had significantly higher post-treatment levels (vs. baseline) of IgG (14.84 +/- 2.61 vs. 12.95 +/- 3.32 g/L, F = 10.458, P = 0.002) and C4 (0.26 +/- 0.09 vs. 0.22 +/- 0.08 g/L, F = 6.835, P = 0.011) and significantly lower IgM (0.86 +/- 0.48 vs. 1.00 +/- 0.42 g/L, F = 9.106, P = 0.003). The patients who developed thyroid disease showed no significant differences in the baseline and post-treatment levels of IgG, C4, or IgM. When the two groups of patients who did or did not develop thyroid disease were compared, there was no difference in the amount of patients who achieved sustained virological response. CONCLUSION: Antiviral-induced thyroid disease in patients with refractory hepatitis C manifests as clinically-detectable abnormalities in serum levels of thyroid autoantibody and markers of hypothyroidism. Levels of other autoantibodies and Igs do not correlate with the development of thyroid disease in these patients, and thyroid disease does not appear to affect the efficacy of Peg-IFN + RBV antiviral therapy.

The efficacy and safety of pegylated interferon α-2b-based immunotherapy for inactive hepatitis B surface antigen carriers.

OBJECTIVES: Pegylated interferon α-2b (PegIFNα-2b) therapy can help inactive hepatitis B surface antigen (HBsAg) carriers (IHCs) achieve clinical cure. To explore and compare the efficacy, safety, and relevant influential factors of PegIFNα-2b monotherapy and PegIFNα-2b-based immunotherapy for IHCs. METHODS: This exploratory, prospective, single-center, randomized controlled trial enrolled 40 IHCs who were randomized into group A (PegIFNα-2b treatment for 68 weeks) and group B (two cycles of PegIFNα-2b treatment with a lead-in period of GM-CSF and vaccine treatment before each cycle). The primary endpoint was 68-week HBsAg loss rate. RESULTS: At week 68, the HBsAg loss rates were 45.45% [full analysis set (FAS)] and 46.67% [per-protocol set (PPS)]. There was no statistically significant difference in HBsAg loss rate between groups A and B ( P  > 0.05). Univariate analysis revealed that age ≤40 years old, baseline HBsAg <200 IU/ml, and 24-week HBsAg decline ≥2 log 10 IU/ml were significantly associated with HBsAg loss in FAS population ( P  < 0.05). Multivariate analysis showed that only 24-week HBsAg decline ≥2 log 10 IU/ml was the independent influencing factor in both FAS and PPS populations ( P  < 0.05). The adverse events were common and mild, and the therapies were well-tolerated. CONCLUSION: Treatment of IHCs with PegIFNα-2b-based therapy could result in a high HBsAg loss rate. The HBsAg loss rate of combined immunotherapy was similar to that of PegIFNα-2b monotherapy, and the safety was good. CLINICALTRIALSGOV ID: NCT05451420.

Rapidly decreased HBV RNA predicts responses of pegylated interferons in HBeAg-positive patients: a longitudinal cohort study.

BACKGROUND: As an important anti-HBV drug, pegylated interferon α (PegIFNα) offers promising clinical efficacy, but biomarkers that accurately forecast treatment responses are yet to be elucidated. Here, we evaluated whether HBV RNA could act as an early monitor of pegylated interferon responses. METHODS: We analyzed a phase 3, multicenter, randomized cohort of 727 HBeAg-positive non-cirrhotic patients receiving a 48-week treatment of PegIFNα-2a or PegIFNα-2b and a 24-week treatment-free follow-up. Serum levels of HBV RNA, HBV DNA, HBeAg, and HBsAg were measured at weeks 0, 12, 24, 48, and 72. RESULTS: HBeAg seroconversion and HBsAg loss at week 72 were observed in 217 (29.8%) and 21 (2.9%) patients, respectively. During the 48-week treatment, HBV RNA decreased more rapidly than HBV DNA and HBsAg, but HBV RNA and HBeAg shared similar dynamics with positive correlations. Multivariate regression analyses consistently revealed the significance of HBV RNA at weeks 0, 12, 24, and 48 to monitor HBeAg seroconversion but not HBsAg loss. Although baseline HBV RNA only showed a modest AUC performance, HBV RNA with a significant increase of AUC at week 12 outperformed other HBV biomarkers to forecast HBeAg seroconversion (p value < 0.05). HBV RNA ≤ 1000 copies/mL was an optimized cutoff at week 12 that offered better prediction than other HBV biomarkers. This optimized cutoff plus patient age, HBV genotype B, and HBeAg offered a strong estimation of HBeAg seroconversion (accuracy 95.2%, true negative rate 99.8%). CONCLUSION: HBV RNA at week 12 is an effective monitor of HBeAg seroconversion in HBeAg-positive patients treated with pegylated interferons.

[Manufacture and evaluation of a spine phantom used in the cross-calibration of DXA bone densitometry].

OBJECTIVE: To design and manufacture a reliable spine phantom used in the cross calibration and quality control of dual X-ray absorptiometry (DXA). METHODS: A hydroxyapatite quality control phantom was designed and made through three steps: solid water, bone phantom material and integration, then evaluated the phantom on four different types of DXA machines made by LUNAR company. RESULTS: Among the four DXA densitometers, the Expert fan beam densitometer had the biggest accuracy errors of bone mineral density (BMD), bone mineral content(BMC) and area values while the other three one narrow fan beam (Prodigy) and two pencil beam densitometers-had small errors. Of the three indexes measured by all the machines, BMD error was the smallest (-15.4%-11.5%), with the Prodigy's BMD was most outstanding. BMD errors at the higher density ends were small, tend to be positive values while the errors at the lower ends were big, tend to be negative. In cross calibration, giving consideration to the differences between the both ends, it is better to use the regression equation to correct. The base line of precision error derived by scanning the phantom once a day for consecutive 25 days was better than that derived by scanning the phantom 25 times consecutively on the same day. As to precision error, the coefficient of variation (CV) of scanning-25 times-a day was the smallest (0.0043) while the CV of 12 adults measurements was the biggest (0.0078). CONCLUSIONS: This phantom can be used in the quality control and cross-calibration of different types of DXA machines.

Preliminary molecular analysis of bacterial composition in periapical lesions with primary endodontic infections of deciduous teeth.

BACKGROUND: The bacterial composition of periapical lesions in deciduous teeth has not been well documented. This study was designed to explore the bacterial compositions, especially the dominant bacteria in periapical lesions using 16S rRNA sequencing. METHODS: Tissue samples were collected from 11 periapical lesions in deciduous teeth with primary endodontic infections. DNA was extracted from each sample and analyzed using 16S rRNA cloning and sequencing for the identification of bacteria. RESULTS: All DNA samples were positive for 16S rRNA gene PCR. One hundred and fifty-one phylotypes from 810 clones were identified to eight phyla, and each sample contained an average of 25.9 phylotypes. In addition, 59 phylotypes were detected in more than two samples, and Fusobacterium (F.) nucleatum (8/11), Dialister (D.) invisus (8/11), Campylobacter (C.) gracilis (7/11), Escherichia (E.) coli DH1 (6/11), Aggregatibacter (A.) segnis (6/11), and Streptococcus (S.) mitis (6/11) were the most prevalent species. Furthermore, 45 as-yet-uncultivated phylotypes were also identified. CONCLUSIONS: Chronic periapical lesions in deciduous teeth contained polymicrobial infections. F. nucleatum, D. invisus, C. gracilis, E. coli DH1, A. segnis, and S. mitis were the most prevalent species detected by 16S rRNA sequencing.