Safety and immunogenicity of the H56:IC31 tuberculosis vaccine candidate in adults successfully treated for drug-susceptible pulmonary TB: a phase 1 randomized trial.

BACKGROUND: H56:IC31 is a candidate vaccine against tuberculosis (TB) with the potential to reduce TB recurrence rate. It is thus important for future clinical trials to demonstrate safety and immunogenicity of H56:IC31 in individuals treated for TB. METHODS: 22 adults confirmed to be Mtb negative (by 2 GeneXpert tests or 2 sputum cultures) after four-five months of TB treatment, and not more than 28 days after completion of TB treatment, were randomized to receive two doses of H56:IC31 (5 mg H56:500 nmol IC31; N=16) or placebo (N=6) 56 days apart. Participants were followed for 420 days for safety and immunogenicity. RESULTS: H56:IC31 vaccination was associated with an acceptable safety profile, consisting mostly of mild self-limited injection site reactions. No serious adverse events, and no vaccine-related severe adverse events, were reported. H56:IC31 induced a CD4+ T-cell response for Ag85B and ESAT-6, with ESAT-6 being immunodominant, which persisted through six months after the last vaccination. There was some evidence of CD8+ T-cell responses for both Ag85B and ESAT-6, but to a lesser extent than CD4+ responses. CONCLUSIONS: H56:IC31 was associated with an acceptable safety profile, and induced a predominant CD4+ T-cell response, in adults recently treated for drug-susceptible, uncomplicated pulmonary TB. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02375698.

Measures of Longitudinal Immune Dysfunction and Risk of AIDS and Non-AIDS Defining Malignancies in Antiretroviral-Treated People With Human Immunodeficiency Virus.

BACKGROUND: Human immunodeficiency virus (HIV) infection leads to chronic immune activation/inflammation that can persist in virally suppressed persons on fully active antiretroviral therapy (ART) and increase risk of malignancies. The prognostic role of low CD4:CD8 ratio and elevated CD8 cell counts on the risk of cancer remains unclear. METHODS: We investigated the association of CD4:CD8 ratio on the hazard of non-AIDS defining malignancy (NADM), AIDS-defining malignancy (ADM) and most frequent group of cancers in ART-treated people with HIV (PWH) with a CD4 and CD8 cell counts and viral load measurements at baseline. We developed Cox proportional hazard models with adjustment for known confounders of cancer risk and time-dependent cumulative and lagged exposures of CD4:CD8 ratio to account for time-evolving risk factors and avoid reverse causality. RESULTS: CD4:CD8 ratios below 0.5, compared to above 1.0, were independently associated with a 12-month time-lagged higher risk of ADM and infection-related malignancies (adjusted hazard ratio 2.61 [95% confidence interval {CI }1.10-6.19] and 2.03 [95% CI 1.24-3.33], respectively). CD4 cell counts below 350 cells/µL were associated with an increased risk of NADMs and ADMs, as did infection, smoking, and body mass index-related malignancies. CONCLUSIONS: In ART-treated PWH low CD4:CD8 ratios were associated with ADM and infection-related cancers independently from CD4 and CD8 cell counts and may alert clinicians for cancer screening and prevention of NADM.

Investigation of Causal Effects of Protein Biomarkers on Cardiovascular Disease in Persons With HIV.

BACKGROUND: There is an incompletely understood increased risk for cardiovascular disease (CVD) among people with HIV (PWH). We investigated if a collection of biomarkers were associated with CVD among PWH. Mendelian randomization (MR) was used to identify potentially causal associations. METHODS: Data from follow-up in 4 large trials among PWH were used to identify 131 incident CVD cases and they were matched to 259 participants without incident CVD (controls). Tests of associations between 460 baseline protein levels and case status were conducted. RESULTS: Univariate analysis found CLEC6A, HGF, IL-6, IL-10RB, and IGFBP7 as being associated with case status and a multivariate model identified 3 of these: CLEC6A (odds ratio [OR] = 1.48, P = .037), HGF (OR = 1.83, P = .012), and IL-6 (OR = 1.45, P = .016). MR methods identified 5 significantly associated proteins: AXL, CHI3L1, GAS6, IL-6RA, and SCGB3A2. CONCLUSIONS: These results implicate inflammatory and fibrotic processes as contributing to CVD. While some of these biomarkers are well established in the general population and in PWH (IL-6 and its receptor), some are novel to PWH (HGF, AXL, and GAS6) and some are novel overall (CLEC6A). Further investigation into the uniqueness of these biomarkers in PWH and the role of these biomarkers as targets among PWH is warranted.

Elevated Levels of Interleukin-1ß and Interleukin-10 Are Associated With Faster Lung Function Decline in People With Well-Treated Human Immunodeficiency Virus.

BACKGROUND: People with human immunodeficiency virus (PWH) have an increased risk of chronic lung diseases and chronic inflammation. We aimed to investigate if inflammatory markers and monocyte activation are associated with faster lung function decline in PWH. METHODS: We included 655 PWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study. Eligible participants were aged ≥25 years and had 2 spirometries separated by >2 years. Inflammatory markers (interleukin [IL]-1ß, IL-2, IL-6, IL-10, tumor necrosis factor-α, and interferon-γ) were measured at baseline by Luminex, and soluble CD14 and soluble CD163 by enzyme-linked immunosorbent assay. Using linear mixed models, we investigated whether elevated cytokine levels were associated with faster lung function decline. RESULTS: The majority of PWH were males (85.2%) with undetectable viral replication (95.3%). We found a faster decline in forced expiratory volume in 1 second (FEV1) in PWH with elevated IL-1ß and IL-10, with an additional decline of 10.3 mL/year (95% confidence interval [CI], 2.1-18.6; P = .014) and 10.0 mL/year (95% CI, 1.8-18.2; P = .017), respectively. We found no interaction between smoking and IL-1ß or IL-10 on FEV1 decline. CONCLUSIONS: Elevated IL-1ß and IL-10 were independently associated with faster lung function decline in PWH, suggesting that dysregulated systemic inflammation may play a role in the pathogenesis of chronic lung diseases.

Qualification of the differential leukocyte count and immunophenotyping in cryopreserved ex vivo whole blood assay.

We developed a flow cytometry-based assay, termed Differential Leukocyte Counting and Immunophenotyping in Cryopreserved Ex vivo whole blood (DLC-ICE), that allows quantification of absolute counts and frequencies of leukocyte subsets and measures expression of activation, phenotypic and functional markers. We evaluated the performance of the DLC-ICE assay by determining inter-operator variability for processing fresh whole blood (WB) from healthy donors collected at multiple clinical sites. In addition, we assessed inter-operator variability for staining of fixed cells and robustness across different anticoagulants. Accuracy was evaluated by comparing DLC-ICE measurements to real-time cell enumeration using an accredited hematology analyzer. Finally, we developed and tested the performance of a 27-colour immunophenotyping panel on cryopreserved fixed WB and compared results to matched fresh WB. Overall, we observed <20% variability in absolute counts and frequencies of granulocytes, monocytes and lymphocytes (T, B and NK cells) when fresh WB was collected in different anti-coagulant tubes, processed or stained by independent operators. Absolute cell counts measured across operators and anti-coagulants using the DLC-ICE method exhibited excellent correlation with the reference method, complete blood count (CBC) with differential, measured using a hematology analyzer (r2 > 0.9 for majority of measurements). A comparison of leukocyte immunophenotyping on fresh WB versus DLC-ICE processed blood yielded equivalent and linear results over a wide dynamic range (r2 = 0.94 over 10-104 cells/µL). These results demonstrate low variability across trained operators, high robustness, linearity and accuracy, supporting utility of the DLC-ICE assay for large cohort studies involving multiple clinical research sites.

Independent Association of Interleukin 6 With Low Dynamic Lung Function and Airflow Limitation in Well-Treated People With Human Immunodeficiency Virus.

BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with an increased risk of chronic pulmonary diseases. We compared cytokine concentrations (interleukin 6 [IL-6], interleukin 1ß, 2, 4, 10, and 17A, tumor necrosis factor α, interferon γ, soluble CD14 [sCD14] and soluble CD163 [sCD163]) in people with HIV (PWH) and uninfected controls and investigated whether elevated cytokine concentrations were independently associated with lung function indices in PWH. METHODS: We performed spirometry and measured cytokine concentrations by Luminex immunoassays or enzyme-linked immunoassay in 951 PWH and 79 uninfected controls from the Copenhagen Comorbidity in HIV Infection study. Regression analyses were used to explore associations between elevated cytokine concentrations and lung function indices. RESULTS: PWH were predominantly male (84.6%) and 94.2% had undetectable viral replication. In PWH, elevated IL-6 was associated with lower forced expiratory volume in 1 second (-212 mL [95% confidence interval, -308 to -116 mL]), lower forced vital capacity (-208 mL [-322 to -93 mL]), and airflow limitation (aOR, 2.62 [1.58-4.36]) (all P < .001) in models adjusted for age, sex, ethnicity, smoking status, body mass index, and CD4 T-cell nadir. The association between IL-6 and dynamic lung function was modified by smoking (P for interaction = .005). CONCLUSION: IL-6 levels were elevated and independently associated with low dynamic lung function and airflow limitation in well-treated PWH, suggesting that systemic inflammation may contribute to the pathogenesis of chronic pulmonary diseases.

Fraction of Exhaled Nitric Oxide Levels Are Elevated in People Living With Human Immunodeficiency Virus Compared to Uninfected Controls, Suggesting Increased Eosinophilic Airway Inflammation.

BACKGROUND: Increased risk of asthma and chronic obstructive pulmonary disease has been reported in people living with human immunodeficiency virus (PLWH). Fraction of exhaled nitric oxide (FeNO) is a marker of eosinophilic airway inflammation. We assessed FeNO levels in PLWH and matched uninfected controls and investigated whether human immunodeficiency virus (HIV) status is independently associated with elevated FeNO. METHODS: FeNO was quantified by NIOX Vero and pulmonary function was assessed by spirometry in 432 PLWH from the Copenhagen Comorbidity in HIV Infection Study and in 1618 age- and sex-matched uninfected controls from the Copenhagen General Population Study. Elevated FeNO was defined as ≥25 parts per billion. Associations between FeNO and HIV status were adjusted for known potential confounders. RESULTS: Mean age of PLWH was 50.7 (standard deviation [SD], 11.1) years and 97.4% received combination antiretroviral therapy. PLWH had higher FeNO than uninfected controls (median, 17.0 [interquartile range {IQR}, 11.0-26.0] vs 13.0 [IQR, 9.0-19.0]; P < .001). Also, PLWH had a higher prevalence of elevated FeNO than uninfected controls (27.5% vs 12.3%; P < .001). This association remained after adjusting for age, sex, height, smoking status, use of airway medication, blood eosinophils, and immunoglobulin E (adjusted OR [aOR], 3.56 [95% CI, 2.51-5.04]; P < .001). Elevated FeNO was associated with self-reported asthma (aOR, 2.65 [95% CI, 1.66-4.24]; P < .001) but not with airflow limitation (aOR, 1.07 [95% CI, .71-1.62]; P = .745). CONCLUSIONS: HIV status was independently associated with elevated FeNO, suggesting increased eosinophilic airway inflammation. The potential impact on chronic lung disease pathogenesis needs further investigation.

The Effect of Interrupted/Deferred Antiretroviral Therapy on Disease Risk: A SMART and START Combined Analysis.

Background: Pooled data from the SMART and START trials were used to compare deferred/intermittent versus immediate/continuous antiretroviral therapy (ART) on disease risk. Methods: Endpoints assessed were AIDS, serious non-AIDS (SNA), cardiovascular disease (CVD), cancer, and death. Pooled (stratified by study) hazard ratios (HRs) from Cox models were obtained for deferred/intermittent ART versus immediate/continuous ART; analyses were conducted to assess consistency of HRs across baseline-defined subgroups. Results: Among 10156 participants, there were 124 AIDS, 247 SNA, 117 cancers, 103 CVD, and 120 deaths. Interventions in each trial led to similar differences in CD4 count and viral suppression. Pooled HRs (95% confidence interval) of deferred/intermittent ART versus immediate/continuous ART were for AIDS 3.63 (2.37-5.56); SNA 1.62 (1.25-2.09); CVD 1.59 (1.07-2.37); cancer 1.93 (1.32-2.83); and death 1.80 (1.24-2.61). Underlying risk was greater in SMART than START. Given the similar HRs for each trial, absolute risk differences between treatment groups were greater in SMART than START. Pooled HRs were similar across subgroups. Conclusions: Treatment group differences in CD4 count and viral suppression were similar in SMART and START. Likely as a consequence, relative differences in risk of AIDS and SNA between immediate/continuous ART and deferred/intermittent ART were similar. Clinical Trials Registration: NCT00027352 and NCT00867048.

Serious Non-AIDS Conditions in HIV: Benefit of Early ART.

PURPOSE OF REVIEW: Optimal control of HIV can be achieved by early diagnosis followed by the initiation of antiretroviral therapy (ART). Two large randomised trials (TEMPRANO and START) have recently been published documenting the clinical benefits to HIV-positive adults of early ART initiation. Main findings are reviewed with a focus on serious non-AIDS (SNA) conditions. RECENT FINDINGS: Data from the two trials demonstrated that initiating ART early in the course of HIV infection resulted in marked reductions in the risk of opportunistic diseases and invasive bacterial infections. This indicates that HIV causes immune impairment in early infection that is remedied by controlling viral replication. Intriguingly, in START, a marked reduction in risk of cancers, both infection-related and unrelated types of cancers, was observed. Like the findings for opportunistic infections, this anti-cancer effect of early ART shows how the immune system influences important pro-oncogenic processes. In START, there was also some evidence suggesting that early ART initiation preserved kidney function, although the clinical consequence of this remains unclear. Conversely, while no adverse effects were evident, the trials did not demonstrate a clear effect on metabolic-related disease outcomes, pulmonary disease, or neurocognitive function. HIV causes immune impairment soon after acquisition of infection. ART reverses this harm at least partially. The biological nature of the immune impairment needs further elucidation, as well as mechanisms and clinical impact of innate immune activation. Based on the findings from TEMPRANO and START, and because ART lowers the risk of onward transmission, ART initiation should be offered to all persons following their diagnosis of HIV.

Eruption of Impacted Teeth after Alveolar Bone Graft in Cleft Lip and Palate Region.

AIM: This study aimed to assess the eruption of impacted teeth in cleft lip and/or palate (CLP) after alveolar bone graft. MATERIALS AND METHODS: Research was carried out through a cross-sectional study at the Craniofacial Rehabilitation Center of the University General Hospital of the University of Cuiaba, Mato Grosso, Brazil. Variables related to cleft, cleft side, gender, age, laterality of cleft, impacted teeth, and orthodontic traction were analyzed. RESULTS: Forty-two patients treated at the institution from 2004 to 2011 were recruited. There were 54.76% males and 45.24% females. The age group between 9 and 11 years was most affected in 59.53% of cases. The unilateral cleft was the most prevalent (85.71%). A total of 57 impacted teeth were observed. Maxillary canine was the most prevalent impacted teeth (97.61%) and more frequent in transforamen incisor cleft (TIC) (76.3%). The orthodontic traction was needed in both maxillary canines and lateral incisor impacted teeth, 64.3 and 35.7% respectively. The orthodontic traction was needed only in TIC (p = 0.0101). CONCLUSION: The canine teeth were the most prevalent, mainly related to the TIC and all impacted teeth erupted spontaneously in the preforamen incisor cleft (PIC) after placement of the bone graft. CLINICAL SIGNIFICANCE: There was spontaneous eruption of impacted teeth after secondary alveolar bone graft in CLP.

Dentogingival Alterations and Their Influence on Facial and Smile Attractiveness.

AIM: This study aimed to evaluate the influence of labial and dentogingival characteristics on facial and smile attractiveness. MATERIALS AND METHODS: Four different close-up photographs each of six women models with different labial and dentogin-gival characteristics were obtained. One of the models was considered standard. Photographs were arranged in an album were evaluated by 100 laypersons, and 30 dentists who ranked each close-up of the models from according to the degree of attractiveness from first to sixth place, with first being the model considered most attractive and justified the reasons for choosing. RESULTS: The standard model received the best scores for both lips (7.75) and face (5.18). Medium-sized lips were preferred (p < 0.05), and the smile positively or negatively interfered with esthetic perception depending on the dentogingival alteration present. Diastema was the alteration that had the greatest negative influence. CONCLUSION: Not all dentogingival alterations interfere with esthetic evaluation. The lips are not decisive in facial attractiveness. Attraction is assessed significantly differently by laypeople than by dentists. The smile directly influences the analysis of facial beauty. CLINICAL SIGNIFICANCE: Dentogingival alterations may be imperceptible, especially when evaluating the facial joint, so its correction will not always be necessary.

Eruption of Impacted Teeth in Cleft Lip and Palate Patients following Alveolar Bone Graft.

INTRODUCTION: This study aimed to assess the eruption of impacted teeth in cleft lip and/or palate (CLP) after alveolar bone graft. MATERIALS AND METHODS: Research was carried out through a cross-sectional study at the Craniofacial Rehabilitation Center of the University General Hospital of the University of Cuiabá, Mato Grosso, Brazil. Variables related to cleft, cleft side, gender, age, laterality of cleft, impacted teeth, and orthodontic traction were analyzed. RESULTS: Forty-two patients treated at the institution from 2004 to 2011 had their charts retrospectively reviewed. They were 54.7% male and 45.2% female. The group aged 9 to 11 years was most affected, representing 59.5% of cases. A unilateral cleft was the most prevalent craniofacial anomaly (85.7%). A total of 57 impacted teeth were observed. Maxillary canines were the most commonly impacted teeth (97.6%) and the most frequently identified in patients with a transforamen incisor cleft (TIC) (76.3%). Orthodontic traction was required for both impacted maxillary canines and impacted lateral incisors (64.3 and 35.7% respectively). The orthodontic traction was required only in patients with a TIC (p = 0.0101). CONCLUSION: The canine teeth were the most commonly impacted teeth, found mainly in patients with a TIC. After placement of the alveolar bone graft in patients with a preforamen incisor cleft (PIC), all impacted teeth erupted spontaneously. CLINICAL SIGNIFICANCE: An impacted tooth can have negative consequences on a patient's quality of life. Thus, a survey evaluating the incidence and prognosis of impacted teeth after an alveolar bone graft for CLP was important.

Effect of the Curing Temperature of Dental Composites evaluated with a Fluorescent Dye.

AIM: With the development of the light-emitting diode (LED) to photo-activate composite resin, greater intensities could be reached without greater elevation of temperature in the mass of the composite resin and in the dental structure arisen from the irradiance in comparison to halogen equipments. This new scenario created a necessity to investigate the influence of temperature over the composite polymerization. MATERIALS AND METHODS: Several curing temperatures (Tcure- 0, 25, 50, 75, and 100°C) were used to polymerize a composite resin (Filtek Z250, 3M ESPE) for 40 and 60 s, using the halogen equipment Gnatus Optilight Digital (halogen) and two LEDs that use a new technology to assembly the diodes: LEC 1000 and bright LEC (MM Optics) (LED 1 and LED 2 respectively). The influence of curing temperature, added by the other variables studied, was evaluated using a methodology developed and improved at IFSC/USP, in which the penetration of a fluorescent dye in the body of the photopolymerized composite resin was quantified using fluorescence spectroscopy. RESULTS: According to the final data submitted to an analysis of variance, the presence of two groups of results could be verified: Between 0 and 25°C, both had a great percentage of the dye penetration compared with other Tcure with a variation in penetration from 69.26 ± 8.19% to 90.99 ± 3.38%. In this analysis, the effects of time and temperature were highly notable (p < 0.05) and the lesser value of dye penetration took place at 60 s of photoactivation This penetration was, in average, smaller with the Tcure of 25°C. The results showed that there was an interaction between the equipment and time and between time and temperature; the other group is regarding the Tcure was from 50, 75, and 100°C, despite the p = 0.05, the effect of temperature was notable. The penetration of the dye ranged from 8.87 ± 3.55 to 39.47 ± 8.9%. The effects of equipment and time were highly notable. The penetration with the time of 60 s was in average smaller. Except with the equipment LED 1, the percentages of the dye penetration were greater with the Tcure of 100°C. The smallest average was the Tcure of 50°C and 60 s of photoactivation. CONCLUSION: Based on the available data regarding the influence of curing temperature on the polymerization process of composite resins, was possible to concluded that small increments of heat increased the degree of conversion. We can assume that the energy supply through the generation of heat by the photopolymerizing devices can function as a heating medium for the reagent system by reducing its viscosity and increasing the mobility and agitation of its components. CLINICAL SIGNIFICANCE: The dentist must be aware of the effects that exist between the activation devices on the light output and their heat transmission to the composite and the tooth itself. This heat transmission might create a polymer with better characteristics.

Antimicrobial Potential of Laser Diode in Infected Dentin.

AIM: To evaluate the antibacterial effect of diode laser, associated or not with 2.5% sodium hypochlorite (NaOCl), against Enterococcus faecalis. MATERIALS AND METHODS: Eighty dentin blocks were obtained from single-rooted human teeth and sterilized. Seventy were inoculated with 0.01 mL of fresh bacterial inoculum (within 24 hours of preparation from pure culture) standardized to 1 McFarland turbidity. Contaminated blocks were incubated for 7 days at 37°C in humid conditions. Ten uncontaminated samples were incubated at 37°C during the contamination period to serve as a negative control group, while 10 of the infected specimens served as a positive control group. The dentin blocks were randomly divided into eight experimental groups (n = 10 each) according to the method of decontamination: 2.5% NaOCl alone; 2.5% NaOCl + photodynamic therapy (PDT) with methylene blue/660 nm laser at 18 J for 180 seconds; 2.5% NaOCl + PDT with methylene blue/660 nm laser at 8 J for 80 seconds; methylene blue alone; PDT alone with methylene blue/660 nm laser at 18 J for 180 seconds; PDT alone with methylene blue/660 nm laser at 8 J laser for 80 seconds; positive control group; and negative control group. Microbial growth was evaluated by culture medium turbidity and microbial concentration was analyzed by UV spectrophotometry (adjusted to read at wavelength l = 600 nM). RESULTS: Root canals treated with laser alone at 18 J for 180 seconds had higher bacterial contamination compared with groups in which NaOCl was used, with or without laser irradiation at 18 J for 180 seconds (p < 0.05). CONCLUSION: Photodynamic therapy with a 660 nm diode laser effectively reduced E. faecalis contamination. These findings can guide development of further studies in search of better alternatives for endodontic treatment. CLINICAL RELEVANCE: Chemical and mechanical root canal preparation plays an essential role in reducing microbial burden. However, microorganisms present in areas not mechanically reachable by endodontic instruments. As an alternative to fix this problem, the laser can be applied.

Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort.

BACKGROUND: Antiretrovirals (ARVs) affect bone density and turnover, but their effect on risk of fractures and osteonecrosis of the femoral head is less understood. We investigated if exposure to ARVs increases the risk of both bone outcomes. METHODS: EuroSIDA participants were followed to assess fractures and osteonecrosis. Poisson regression identified clinical, laboratory and demographic predictors of either bone outcome. Ever, current, and cumulative exposures to ARVs were assessed. RESULTS: During 86118 PYFU among 11820 included persons (median age 41y, 75% male, median baseline CD4 440/mm3, 70.4% virologically suppressed), there were 619 fractures (incidence/1000 PYFU 7.2; 95% CI 6.6-7.7) and 89 osteonecrosis (1.0; 0.8-1.3). Older age, white race, lower BMI, IV drug use, lower baseline CD4, HCV coinfection, prior osteonecrosis, prior fracture, cardiovascular disease, and recent non-AIDS cancer (last 12 months) were associated with fractures. After adjustment, persons who had ever used tenofovir disoproxil fumarate (TDF) (1.40; 1.15-1.70) or who were currently on TDF (1.25; 1.05-1.49) had higher incidence of fractures. There was no association between cumulative exposure to TDF and fractures (1.08/5 y exposure; 0.94-1.25). No other ARV was associated with fractures (all P > .1). Risk of osteonecrosis was associated with white race, lower nadir CD4, prior osteonecrosis, prior fracture, and prior AIDS. After mutual adjustment, no ARV was associated with osteonecrosis. CONCLUSIONS: In human immunodeficiency virus (HIV) infection, host factors, HIV-specific variables, and comorbidities contribute to risk of fractures and osteonecrosis. Exposure to TDF, but not other ARVs, was an independent risk factor for fractures.

Effects of the Ratio between Pigment and Bleaching Gel on the Fracture Resistance and Dentin Microhardness of endodontically treated Teeth.

INTRODUCTION: The aim of this study was to evaluate the effects of bleaching gel using 35% hydrogen peroxide (HP), associated with red carmine pigment (RC), in the 3:1 or 1:1 ratio, on fracture resistance and dentin microhardness of endodontically treated teeth. MATERIALS AND METHODS: A total of 40 lower incisors were endodontically treated and divided into four groups (n = 10), according to the bleaching protocol: G1 (HP3), 35% HP + RC (3:1); G2 (HP1), 35% HP + RC (1:1); G3 (positive), 38% HP; and G4 (negative), unbleached. Four dental bleaching sessions were performed. The dental crowns were restored after the last session and submitted to the fracture resistance test. Totally, 60 specimens from the endodontically treated lower incisor crowns were prepared to evaluate the effects on dentin microhardness. The analysis was measured (in Knoop) prior to and after the last dental bleaching session using similar bleaching protocols. RESULTS: G2 presented the lowest fracture resistance (p < 0.05). The other groups were similar to each other (p > 0.05). No difference was observed in the reduction of dentin microhardness among the groups (p > 0.05). CONCLUSION: A 1:1 ratio (bleaching gel:pigment) caused a significant fracture resistance reduction in relation to the other protocols. No effect on the dentin microhardness reduction was observed. CLINICAL SIGNIFICANCE: The pigment addition to the bleaching agent accelerates the bleaching chemical reaction. However, no studies have evaluated the ideal proportion to optimize tooth bleaching.

Interleukin 6 Is a Stronger Predictor of Clinical Events Than High-Sensitivity C-Reactive Protein or D-Dimer During HIV Infection.

BACKGROUND: Interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP), and D-dimer levels are linked to adverse outcomes in human immunodeficiency virus (HIV) infection, but the strength of their associations with different clinical end points warrants investigation. METHODS: Participants receiving standard of care in 2 HIV trials with measured biomarker levels were followed to ascertain all-cause death, non-AIDS-related death, AIDS, cardiovascular disease (CVD), and non-AIDS-defining malignancies. Hazard ratios (HRs) and 95% confidence intervals (CIs) of each end point for quartiles and log2-transformed IL-6, hsCRP, and D-dimer levels were calculated using Cox models. Marginal models modelling multiple events tested for equal effects of biomarker levels on different end points. RESULTS: Among 4304 participants, there were 157 all-cause deaths, 117 non-AIDS-related deaths, 101 AIDS cases, 121 CVD cases, and 99 non-AIDS-defining malignancies. IL-6 was more strongly associated with most end points, compared with hsCRP. IL-6 appeared to be a stronger predictor than D-dimer for CVD and non-AIDS-defining malignancies, but 95% CIs overlapped. Independent associations of IL-6 were stronger for non-AIDS-related death (HR, 1.71; 95% CI, 1.43-2.04) and all-cause death (HR, 1.56; 95% CI, 1.33-1.84) and similar for CVD (HR, 1.35; 95% CI, 1.12-1.62) and non-AIDS-defining malignancies (HR, 1.30; 95% CI, 1.06-1.61). There was heterogeneity of IL-6 (P < .001) but not hsCRP (P = .15) or D-dimer (P = .20) as a predictor for different end points. CONCLUSIONS: IL-6 is a stronger predictor of fatal events than of CVD and non-AIDS-defining malignancies. Adjuvant antiinflammatory and antithrombotic therapies should be tested in HIV-infected individuals.

Immediate Antiretroviral Therapy Reduces Risk of Infection-Related Cancer During Early HIV Infection.

BACKGROUND: In the Strategic Timing of Antiretroviral Treatment (START) study, immediate combination antiretroviral therapy (cART) initiation reduced cancer risk by 64%. We hypothesized that risk reduction was higher for infection-related cancer and determined by differences in CD4 cell counts and human immunodeficiency virus (HIV) RNA between the study arms. METHODS: Incident malignancies in START were categorized into infection-related and infection-unrelated cancer. We used Cox models to assess factors associated with both cancer categories. We used sequential adjustment for baseline covariates, cancer risk factors, and HIV-specific variables to investigate potential mediators of cancer risk reduction with immediate cART. RESULTS: There were 14 cancers among persons randomized to immediate cART (6 infection-related and 8 infection-unrelated) and 39 cancers in the deferred arm (23 infection-related and 16 infection-unrelated); hazard ratios of immediate vs deferred cART initiation were 0.26 (95% confidence interval [CI], .11-.64) for infection-related and 0.49 (95% CI, .21-1.15) for infection-unrelated cancer. Independent predictors of infection-related cancer were older age, higher body mass index, low- to middle-income region, HIV RNA, and baseline CD8 cell count. Older age and baseline CD8 cell count were independent predictors of infection-unrelated cancer. Adjustment for latest HIV RNA level had little impact on the protective effect of immediate cART on infection-related cancer. Adjustment for latest HIV RNA level, but not for CD4 cell count or cancer risk factors, attenuated the effect of immediate cART on infection-unrelated cancer. CONCLUSIONS: Immediate cART initiation significantly reduces risk of cancer. Although limited by small sample size, this benefit does not appear to be solely attributable to HIV RNA suppression and may be also mediated by other mechanisms.

Nonnucleoside Reverse-transcriptase Inhibitor- vs Ritonavir-boosted Protease Inhibitor-based Regimens for Initial Treatment of HIV Infection: A Systematic Review and Metaanalysis of Randomized Trials.

BACKGROUND: Previous studies suggest that nonnucleoside reverse-transcriptase inhibitors (NNRTIs) cause faster virologic suppression, while ritonavir-boosted protease inhibitors (PI/r) recover more CD4 cells. However, individual trials have not been powered to compare clinical outcomes. METHODS: We searched databases to identify randomized trials that compared NNRTI- vs PI/r-based initial therapy. A metaanalysis calculated risk ratios (RRs) or mean differences (MDs), as appropriate. Primary outcome was death or progression to AIDS. Secondary outcomes were death, progression to AIDS, and treatment discontinuation. We calculated RR of virologic suppression and MD for an increase in CD4 cells at week 48. RESULTS: We included 29 trials with 9047 participants. Death or progression to AIDS occurred in 226 participants in the NNRTI arm and in 221 in the PI/r arm (RR, 1.03; 95% confidence interval, .87-1.22; 12 trials; n = 3825), death in 205 participants in the NNRTI arm vs 198 in the PI/r arm (1.04; 0.86-1.25; 22 trials; n = 8311), and progression to AIDS in 140 participants in the NNRTI arm vs 144 in the PI/r arm (1.00; 0.80-1.25; 13 trials; n = 4740). Overall treatment discontinuation (1.12; 0.93-1.35; 24 trials; n = 8249) and from toxicity (1.21; 0.87-1.68; 21 trials; n = 6195) were comparable, but discontinuation due to virologic failure was more common with NNRTI (1.58; 0.91-2.74; 17 trials; n = 5371). At week 48, there was no difference between NNRTI and PI/r in virologic suppression (RR, 1.03; 0.98-1.09) or CD4(+) recovery (MD, -4.7 cells; -14.2 to 4.8). CONCLUSIONS: We found no difference in clinical and viro-immunologic outcomes between NNRTI- and PI/r-based therapy.

Status of Endodontic Treatment and the Correlations to the Quality of Root Canal Filling and Coronal Restoration.

INTRODUCTION: This cross-sectional study evaluated the prevalence and quality of root canal treatment in 1,977 digital radiological files. MATERIALS AND METHODS: Data were statistically analyzed using descriptive analysis, and the chi-square test was performed with a 5% significance level. RESULTS: The mean age of the study population was 34.9 years. The endodontic treatment frequency was 6.14%, significantly higher in premolars. Adequate endodontic treatment was observed in 39.7% of analyzed cases. Molars were significantly more frequent with regard to inadequate filling quality. In 47.6% of cases, the filling's apical limit was classified as adequate, and there was a higher incidence of molars that were inadequate. Restorations were classified as adequate in 79.0% of cases, and molars were responsible for the highest frequency of inadequate restorations. The frequency of teeth with endodontic treatment that showed no periapical changes was 47.7%. There was no significant difference in the presence of periapical change according to gender. An increased presence of periapical change was observed with increasing age. The periapical lesions were observed in 45% of cases and related to inadequate filling quality. The apical limit was considered inadequate and related to periapical changes in 42% of cases. Periapical changes were present in 52% of cases, regardless of the quality of the filling and apical limit. Such changes were present in 42% of cases with adequate coronal restoration. CONCLUSION: It can be concluded that apical periodontitis (AP) is associated with the quality of endodontic treatment. The coronal restoration affects significantly the success rate of endodontic treatment. CLINICAL SIGNIFICANCE: The quality of the root filling and coronal restoration is closely related to periapical health.