Complement activation and blockade in massive post-partum haemorrhage, thrombotic microangiopathy and acute kidney injury: a case report.

BACKGROUND: Thrombotic microangiopathy (TMA)-mediated acute kidney injury (AKI) following massive haemorrhage is a rare but severe complication of the post-partum period. It is associated with a poor renal prognosis and a high risk of end-stage kidney disease. Complement activation may occur in this picture. However, whether complement activation, and thus complement blockade, may be critically relevant in this setting is unknown. CASE PRESENTATION: A 50 year-old woman presented with massive delayed post-partum haemorrhage (PPH). Despite bleeding control and normalization of coagulation parameters, she rapidly developed AKI stage 3 associated with dysmorphic microhematuria and proteinuria up to 2 g/day with the need of renal replacement therapy. Blood tests showed signs of TMA associated with markedly increased sC5b-9 and factor Bb plasma levels, respectively markers of terminal and alternative complement pathway over-activation. This clinical picture prompted us to initiate anti-C5 therapy. sC5b-9 normalized within 12 h after the first dose of eculizumab, factor Bb and C3 after seven days, platelet count after nine days and haptoglobin after 3 weeks. The clinical picture improved rapidly with blood pressure control within 48 h. Diuresis resumed after three days, kidney function rapidly improved and haemodialysis could be discontinued after the sixth and last dose. Serum creatinine returned to normal two years after presentation. CONCLUSIONS: We suggest that massive PPH induced major activation of complement pathways, which ultimately lead to TMA-induced AKI. Various causes, such as oocyte-donation, the potential retention of placental material and the use of tranexamic acid may have contributed to complement activation due to PPH. The prompt administration of anti-C5 therapy may have rapidly restored kidney microcirculation patency, thus reversing signs of TMA and AKI. We propose that complement activation may represent a major pathophysiological player of this complication and may provide a novel therapeutic avenue to improve renal prognosis in TMA-induced AKI following massive PPH.

A Randomized Placebo-Controlled Efficacy Study of a Prime Boost Therapeutic Vaccination Strategy in HIV-1-Infected Individuals: VRI02 ANRS 149 LIGHT Phase II Trial.

In this placebo-controlled phase II randomized clinical trial, 103 human immunodeficiency virus type 1 (HIV-1)-infected patients under cART (combined antiretroviral treatment) were randomized 2:1 to receive either 3 doses of DNA GTU-MultiHIV B (coding for Rev, Nef, Tat, Gag, and gp160) at week 0 (W0), W4, and W12, followed by 2 doses of LIPO-5 vaccine containing long peptides from Gag, Pol, and Nef at W20 and W24, or placebo. Analytical treatment interruption (ATI) was performed between W36 to W48. At W28, vaccinees experienced an increase in functional CD4+ T-cell responses (P < 0.001 for each cytokine compared to W0) measured, predominantly against Gag and Pol/Env, and an increase in HIV-specific CD8+ T cells producing interleukin 2 (IL-2) and tumor necrosis factor alpha (TNF-α) (P = 0.001 and 0.013, respectively), predominantly against Pol/Env and Nef. However, analysis of T-cell subsets by mass cytometry in a subpopulation showed an increase in the W28/W0 ratio for memory CD8+ T cells coexpressing exhaustion and senescence markers such as PD-1/TIGIT (P = 0.004) and CD27/CD57 (P = 0.044) in vaccinees compared to the placebo group. During ATI, all patients experienced viral rebound, with the maximum observed HIV RNA level at W42 (median, 4.63 log10 copies [cp]/ml; interquartile range [IQR], 4.00 to 5.09), without any difference between arms. No patient resumed cART for CD4 cell count drop. Globally, the vaccine strategy was safe. However, a secondary HIV transmission during ATI was observed. These data show that the prime-boost combination of DNA and LIPO-5 vaccines elicited broad and polyfunctional T cells. The contrast between the quality of immune responses and the lack of potent viral control underscores the need for combined immunomodulatory strategies. (This study has been registered at ClinicalTrials.gov under registration no. NCT01492985.)IMPORTANCE In this placebo-controlled phase II randomized clinical trial, we evaluated the safety and immunogenicity of a therapeutic prime-boost vaccine strategy using a recombinant DNA vaccine (GTU-MultiHIV B clade) followed by a boost vaccination with a lipopeptide vaccine (HIV-LIPO-5) in HIV-infected patients on combined antiretroviral therapy. We show here that this prime-boost strategy is well tolerated, consistently with previous studies in HIV-1-infected individuals and healthy volunteers who received each vaccine component individually. Compared to the placebo group, vaccinees elicited strong and polyfunctional HIV-specific CD4+ and CD8+ T-cell responses. However, these immune responses presented some qualitative defects and were not able to control viremia following antiretroviral treatment interruption, as no difference in HIV viral rebound was observed in the vaccine and placebo groups. Several lessons were learned from these results, pointing out the urgent need to combine vaccine strategies with other immune-based interventions.

CO2 laser and the genitourinary syndrome of menopause: a randomized sham-controlled trial.

PURPOSE: This study aimed to clarify the efficacy of intravaginal CO2-laser treatment in postmenopausal women with genitourinary syndrome of menopause (GSM). MATERIALS AND METHODS: This double-blind, randomized, sham-controlled trial included postmenopausal women diagnosed with GSM and bothersome dryness and dyspareunia. Treatment consisted of three sessions. Active CO2-laser treatments (active group) were compared to sham treatments (sham group) with the primary endpoints being changes in dryness and dyspareunia intensity, as assessed by the 10-cm visual analog scale. Secondary endpoints were as follows: changes in Female Sexual Function Index (FSFI; total score and all domains), itching, burning, dysuria, and Urogenital Distress Inventory (UDI-6); incidence of symptoms; and presence of adverse events. All outcomes were evaluated at baseline and 4 months post baseline. RESULTS: Fifty-eight women (28 in the active group and 30 in the sham group) were eligible for inclusion. In the active group, dryness, dyspareunia, FSFI (total score), itching, burning, dysuria, and UDI-6 were significantly improved (mean [standard deviation] -5.6 [2.8], -6 [2.6], 12.3 [8.9], -2.9 [2.8], -2.3 [2.8], -0.9 [2.1], and -8.0 [15.3], respectively). In the sham group, dryness, itching, and burning were significantly improved (-1.9 [2], -1.4 [1.9], and -1 [1.9], respectively). All changes were in favor of the active group. After completion of the protocol, the proportion of participants with dryness, dyspareunia, and sexual dysfunction was significantly lower in the active group compared to those in the sham group (all p < 0.005). CONCLUSIONS: CO2 laser could be proposed as an effective alternative treatment for the management of GSM as it is superior to sham treatments.

Dental implants survival rate in controlled type I diabetic patients: a prospective longitudinal study with a 2-year follow-up.

The aim of the study was to evaluate implant treatment for partial edentulism in a population of controlled type I diabetic patients. The research hypothesis was that implant survival rate, prevalence of peri-implant tissue infection and marginal bone loss at 2 years follow-up would not differ from a non diabetic population. A total of 106 patients (47=women, 59=men, mean age 38.36 years) presented with partially edentulous jaws. All patients underwent a two stage implant surgery (105 maxillary, 100 mandibular). Diabetic type I patients (53) were scheduled in Group A, while 53 healthy patients formed the Control Group. Clinical and radiological controls were performed from baseline up to 24 months and implants survival rate, presence of peri-implant tissue infections and marginal bone loss were assessed in all ptients. Group A and Control Group were compared by analyzing data at implant level, through either an independent sample t-test, with respect to bone loss, or Fisher Exact tests, with respect to (a) peri-implant mucositis, (b) peri-implantitis, and (c) post-operative wound infection. At the 24-month follow-up, 5 and 3 implants failed in diabetic and non-diabetic patients, respectively. No statistically significant difference was found in implant survival rate between the two groups (Group A: 95.19%; Control Group: 97.03%). Moreover, no statistical significant differences were found in infections occurrence, nor in marginal bone loss. The preliminary results of this prospective study showed how implant treatment for partial edentulism may a be safe and predictable procedure for diabetic type I patients, provided controlled glycemic levels and regular professional oral hygiene sessions.

Recombinant HIV-1 vaccine candidates based on replication-defective flavivirus vector.

Multiple approaches utilizing viral and DNA vectors have shown promise in the development of an effective vaccine against HIV. In this study, an alternative replication-defective flavivirus vector, RepliVax (RV), was evaluated for the delivery of HIV-1 immunogens. Recombinant RV-HIV viruses were engineered to stably express clade C virus Gag and Env (gp120TM) proteins and propagated in Vero helper cells. RV-based vectors enabled efficient expression and correct maturation of Gag and gp120TM proteins, were apathogenic in a sensitive suckling mouse neurovirulence test, and were similar in immunogenicity to recombinant poxvirus NYVAC-HIV vectors in homologous or heterologous prime-boost combinations in mice. In a pilot NHP study, immunogenicity of RV-HIV viruses used as a prime or boost for DNA or NYVAC candidates was compared to a DNA prime/NYVAC boost benchmark scheme when administered together with adjuvanted gp120 protein. Similar neutralizing antibody titers, binding IgG titers measured against a broad panel of Env and Gag antigens, and ADCC responses were observed in the groups throughout the course of the study, and T cell responses were elicited. The entire data demonstrate that RV vectors have the potential as novel HIV-1 vaccine components for use in combination with other promising candidates to develop new effective vaccination strategies.

Accuracy of Periapical Radiography and CBCT in Endodontic Evaluation.

INTRODUCTION: A radiological evaluation is essential in endodontics, for diagnostic purposes, planning and execution of the treatment, and evaluation of the success of therapy. The periapical radiography is nowadays the main radiographic investigations used but presents some limits as 3D anatomic alteration, geometric compression, and possible anatomical structures overlapping that can obscure the area of interest. CBCT (cone beam computed tomography) in endodontics allows a detailed assessment of the teeth and surrounding alveolar anatomy for endodontic diagnosis, treatment planning, and follow-up. OBJECTIVE: The purpose of this study was to evaluate the accuracy of CBCT in comparison with conventional intraoral radiographs used in endodontic procedures. MATERIALS AND METHODS: Statistical analysis was performed on 101 patients with previous endodontic treatments with the relative radiographic documentation (preoperative, postoperative, and follow-up intraoral X-ray) that had underwent at CBCT screening for surgical reasons. The CBCT scans were evaluated independently by two operators and compared with the corresponding periapical images. RESULTS: Our analysis shows that the two radiological investigations statistically agree in 100% of cases in the group of patients without any endodontic sign. In the group of patients with an endodontic pathology, detected with CBCT, endodontic under extended treatments (30.6%), MB2 canals in nontreated maxillary molars (20.7%), second canals in nontreated mandibular incisors (9%), root fractures (2.7%), and root resorption (2.7%) were not always visible in intraoral X-ray. Otherwise, positivity in the intraoral X-ray was always confirmed in CBCT. A radiolucent area was detected in CBCT exam in 46%, while the intraoral X-ray exam was positive only in 18%. CONCLUSIONS: Our study shows that some important radiological signs acquired using CBCT are not always visible in periapical X-ray. Furthermore, CBCT is considered as a II level exam and could be used to solve diagnostic questions, essential to a proper management of the endodontic problems.

The association between minor recurrent aphthous stomatitis (RAS), children's poor oral condition, and underlying negative psychosocial habits and attitudes towards oral hygiene.

BACKGROUND: Minor Recurrent Aphthous Stomatitis (RAS) represents a disease which is very difficult to prevent. This case-control study focused on possible associations between minor Recurrent Aphthous Stomatitis in children, their oral health, and underlying behavioral indexes of children's attitudes and habits pertaining to (home) oral hygiene, with the further goal of enabling the dentist to prevent these specific kind of lesions, both from a clinical and a broader psychosocial perspective. METHODS: Four hundred one school-children (5-10 years old) in Milan (Italy) were submitted to an intra-oral examination, and interviewed with the aid of a brief psychosocial questionnaire. RESULTS: At the clinical level, statistically significant associations were observed between the presence of decayed teeth and minor Recurrent Aphthous Stomatitis (Odds Ratio: 3.15; 95% CI: lower limit 1.06; upper limit: 9.36; Z-test: 2.07, p = 0.039; Chi-square = 4.71, p = 0.030), and between the Decayed Missing or Filled Teeth (DMFT) index and minor aphthous stomatitis (Odds Ratio: 3.30; 95% CI: lower limit 1.13; upper limit: 9.67; Z-test = 2.18, p = 0.029; Chi-square = 5.27; p = 0.022), both results pointing to a significant increase-by circa 3 times-in the risk of developing minor Recurrent Aphthous Stomatitis in children exposed to the two above-identified factors (i.e., the presence of decayed teeth and a clearly compromised oral condition, as signaled by the DMFT index), if compared with the risk run by their non-exposed counterparts. At the psychosocial level of analysis, statistically significant associations were observed (1) between children's practice of spontaneously brushing teeth when not at home and a comparatively lower (i.e. better) Decayed Missing or Filled Teeth index (Chi-square: 8.95; p = 0.011), and (2) between receiving parental aid (e.g., proper brushing instructions) while practicing home oral hygiene and a significantly reduced presence of decayed teeth (Chi-square = 5.40; p = .067; Spearman's Rho, p = .038). Further, significant associations were also observed between children's reported severity of dental pain and both (a) the presence of decayed teeth (Chi-square = 10.80; p = 0.011), and (b) children's (poor) oral health condition as expressed by the Decayed Missing or Filled Teeth index (Chi-square = 6.29; p = 0.043). Interestingly, specific lifestyles and social status, showed no systematic association to other clinical or psychological/psychosocial indices. CONCLUSIONS: These systematic relations suggest that, in the presence of Recurrent Aphthous Stomatitis in pediatric patients, the dentist should carefully monitor children for potential carious lesions, implement protocols of prevention to control Recurrent Aphthous Stomatitis disease in children affected by caries, and also be particularly aware of the right or wrong habits children may acquire in the course of continued social exchange with their caregivers and peers.

Thermafil: A New Clinical Approach Due to New Dimensional Evaluations.

BACKGROUND: There are a lot of techniques to obturate the root canals, but lateral condensation of gutta-percha is the most used one. An important aspect of thermafil is the error margin tolerated by the manufacturer in the production of plastic carriers. In literature, there is no evidence about discrepancy percentage between different carriers. It is demonstrated that the error margin of gutta-percha is 0.5% and is 0.2% for metal files (ISO standards). OBJECTIVE: The aim of this study was to evaluate the real dimensions of thermafil plastic carriers observed by the stereo microscope measuring the dimensional discrepancy between them. METHODS: For this study, 80 new thermafil (Dentsply Maillefer) have been selected. 40 thermafil 0.25 and 40 thermafil 0.30. Through 60X stereo microscope, the dimensions of the plastic carrier tips have been measured. The dimensions of the plastic carrier were also measured after a heating cycle. ZL GAL 11TUSM (Zetaline stereo evolution) microscope was used to observe the samples. Measurements were made through a dedicated software (Image Focus). All samples were analysed at 60X. RESULTS: A non-parametric paired test (Wilcoxon test) was used to compare baseline and after heating values; p-values ≤ 0.05 were assumed to be statistically significant. CONCLUSION: The samples we measured showed a mean value of the diameters in Thermafil 25 that was 0.27 mm, for Thermafil 30 the mean value was 0.33 mm.We have measured a dimensional variable of 8% in the 25 group while in group 30 the maximum possible variation found was 4%, that's why we propose a new protocol of obturation with thermafil. We can also conclude that a single heating process does not affect clinically the plastic carrier dimensions.

The association between three attitude-related indexes of oral hygiene and secondary implant failures: A retrospective longitudinal study.

OBJECTIVE: This study evaluated the strength of the association between three widely used clinical indexes considered as distal behavioural indicators of attitude-related oral status (an index of oral hygiene, the plaque index [PI] and two periodontal indexes, that is the presence of bleeding on probing [BOP] and of pockets probing depth [PPD]) and secondary implant failure due to peri-implantitis in patients rehabilitated with cemented prosthesis. MATERIALS AND METHODS: The study included patients who underwent implant-prosthetic rehabilitation and had joined the programme of maintenance of the same hospital. Implant failures, number of months between implant insertion and implant loading, and patients' surgical protocol were monitored and recorded. Further, PI, BOP and PPD-all attitude-related indicators of oral hygiene and periodontal inflammation-were recorded and related, in terms of odds ratios (ORs ) and corresponding risk factors, to secondary implant failures. RESULTS: A total of 1427 patients (2673 implants) were enrolled. The follow-up ranged from 1.5 to 9 years (mean 5.3 years±1.3). The cumulative survival rate was 98.01%. Thirty-two patients (36 implants, 1.36% of all implants) had implant failure. A statistically significant association between PI, BOP, PPD and secondary failures due to peri-implantitis was observed. CONCLUSION: Within the limitations of this study, all three attitude-related behavioural indicators-the plaque index (PI), bleeding on probing (BOP) and abnormal probing pocket depth (PPD)-proved to be significant risk indicators for secondary implant failure due to peri-implantitis, both from a clinical and from a socio-psychological attitude-related perspective.

Sequential Vacc-4x and romidepsin during combination antiretroviral therapy (cART): Immune responses to Vacc-4x regions on p24 and changes in HIV reservoirs.

OBJECTIVES: The REDUC clinical study Part B investigated Vacc-4x/rhuGM-CSF therapeutic vaccination prior to HIV latency reversal using romidepsin. The main finding was a statistically significant reduction from baseline in viral reservoir measurements. Here we evaluated HIV-specific functional T-cell responses following Vacc-4x/rhuGM-CSF immunotherapy in relation to virological outcomes on the HIV reservoir. METHODS: This study, conducted in Aarhus, Denmark, enrolled participants (n = 20) with CD4>500 cells/mm3 on cART. Six Vacc-4x (1.2 mg) intradermal immunizations using rhuGM-CSF (60 µg) as adjuvant were followed by 3 weekly intravenous infusions of romidepsin (5 mg/m2). Immune responses were determined by IFN-γ ELISpot, T-cell proliferation to p24 15-mer peptides covering the Vacc-4x region, intracellular cytokine staining (ICS) to the entire HIVGag and viral inhibition. RESULTS: The frequency of participants with CD8+ T-cell proliferation assay positivity was 8/16 (50%) at baseline, 11/15 (73%) post-vaccination, 6/14 (43%) during romidepsin, and 9/15 (60%)post-romidepsin. Participants with CD8+ T-cell proliferation assay positivity post-vaccination showed reductions in total HIV DNA post-vaccination (p = 0.006; q = 0.183), post-latency reversal (p = 0.005; q = 0.183), and CA-RNA reductions post-vaccination (p = 0.015; q = 0.254). Participants (40%) were defined as proliferation 'Responders' having ≥2-fold increase in assay positivity post-baseline. Robust ELISpot baseline responses were found in 87.5% participants. No significant changes were observed in the proportion of polyfunctional CD8+ T-cells to HIVGag by ICS. There was a trend towards increased viral inhibition from baseline to post-vaccination (p = 0.08). CONCLUSIONS: In this 'shock and kill' approach supported by therapeutic vaccination, CD8+ T-cell proliferation represents a valuable means to monitor functional immune responses as part of the path towards functional HIV cure.

Identification of a novel HLA-B*18 allele, B*18:119, using sequence-based typing in a caucasoid individual.

HLA-B*18:119 differs from HLA-B*18:01:01 at nucleotide 28 C>T in exon 4 changing histidine to tyrosine.

Clinical and Spectrophotometric Evaluation of LED and Laser Activated Teeth Bleaching.

BACKGROUND: Auxiliary power sources (LED and laser) are used in in-office teeth bleaching techniques to accelerate the redox reaction of the whitening gel to increase ease of use, to improve comfort and safety, and to decrease the procedure time. OBJECTIVE: The aim this study is to evaluate the efficiency of the teeth whitening procedures performed with hydrogen peroxide and carbamide peroxide, LED or Laser activated. METHOD: 18 patients, affected by exogenous dyschromia, were treated with a bleaching agent composed by 35% hydrogen peroxide and 10% carbamide peroxide. They were divided into two groups: in the first group the bleaching agent was activated by a LED lamp; in the second group it was activated by a Laser diode lamp. Both groups were subjected to 3 bleaching cycle of 15' each. The chromatic evaluations were performed before and after one week from the treatment, using a chromatic scale and a spectrophotometer. The mean value of pre, post bleaching and follow-up were analyzed using a T-test, with results statistically significant for P<0,05. RESULTS: Results showed that the variations in brightness, chroma and hue are significantly influenced by the interaction between the whitening agent and the original colour of the teeth. Laser-activation has marginally improved the bleaching effectiveness. All patients treated with laser activation complained an increase in dental sensitivity. CONCLUSION: The use of laser-activating systems did not improve the efficacy of bleaching.

Transcrestal Sinus Lift Procedure Approaching Atrophic Maxillary Ridge: A 60-Month Clinical and Radiological Follow-Up Evaluation.

Aim. The aim of this study was to assess the success and the survival rate of dental implants placed in augmented bone after sinus lifting procedures. Material and Methods. 31 patients were mainly enrolled for a residual upper jaw crest thickness of 3 mm. CBCT scans were performed before and after the augmentation technique and at the follow-up appointments, at 3, 6, 12, 24, and up to 60 months. The follow-up examination included cumulative survival rate of implants, peri-implant marginal bone loss, and the height of sinus floor augmentation. Results. This retrospective study on 31 patients and 45 implants later inserted in a less than 3 mm crest showed excellent survival rates (99.5%), one implant was lost before loading due to an acute infection after 24 days, and two implants did not osteointegrate and were removed after 3 months. The radiological evaluation showed an average bone loss of 0.25 mm (±0.78 mm) at the first follow-up appointment (3 months) up to 0.30 mm (±1.28 mm) after 60-month follow-up. Conclusion. In this study it was reported how even in less than 3 mm thick crest a transcrestal technique can predictably be used with a long-term clinical and radiological outcome, giving patients excellent stability of the grafted material and healthy clinical results.

Increases in Condomless Sex in the Swiss HIV Cohort Study.

Condomless sex is a key driver of sexually transmitted diseases. In this study, we assess the long-term changes (2000-2013) of the occurrence of condomless sex among human immunodeficiency virus (HIV)-infected individuals enrolled in the Swiss HIV Cohort study. The frequencies with which HIV-infected individuals reported condomless sex were either stable or only weakly increasing for 2000-2008. For 2008-2013, these rates increased significantly for stable relationships among heterosexuals and men who have sex with men (MSM) and for occasional relationships among MSM. Our results highlight the increasing public health challenge posed by condomless sex and show that condomless sex has been increasing even in the most recent years.

Obesity Trends and Body Mass Index Changes After Starting Antiretroviral Treatment: The Swiss HIV Cohort Study.

BACKGROUND: The factors that contribute to increasing obesity rates in human immunodeficiency virus (HIV)-positive persons and to body mass index (BMI) increase that typically occurs after starting antiretroviral therapy (ART) are incompletely characterized. METHODS: We describe BMI trends in the entire Swiss HIV Cohort Study (SHCS) population and investigate the effects of demographics, HIV-related factors, and ART on BMI change in participants with data available before and 4 years after first starting ART. RESULTS: In the SHCS, overweight/obesity prevalence increased from 13% in 1990 (n = 1641) to 38% in 2012 (n = 8150). In the participants starting ART (n = 1601), mean BMI increase was 0.92 kg/m(2) per year (95% confidence interval, .83-1.0) during year 0-1 and 0.31 kg/m(2) per year (0.29-0.34) during years 1-4. In multivariable analyses, annualized BMI change during year 0-1 was associated with older age (0.15 [0.06-0.24] kg/m(2)) and CD4 nadir <199 cells/µL compared to nadir >350 (P < .001). Annualized BMI change during years 1-4 was associated with CD4 nadir <100 cells/µL compared to nadir >350 (P = .001) and black compared to white ethnicity (0.28 [0.16-0.37] kg/m(2)). Individual ART combinations differed little in their contribution to BMI change. CONCLUSIONS: Increasing obesity rates in the SHCS over time occurred at the same time as aging of the SHCS population, demographic changes, earlier ART start, and increasingly widespread ART coverage. Body mass index increase after ART start was typically biphasic, the BMI increase in year 0-1 being as large as the increase in years 1-4 combined. The effect of ART regimen on BMI change was limited.

Performance evaluation of a new fourth-generation HIV combination antigen-antibody assay.

Education and diagnostic tests capable of early detection represent our most effective means of preventing transmission of human immunodeficiency virus (HIV). The importance of early detection is underlined by studies demonstrating increased life expectancy following early initiation of antiviral treatment. The Elecsys(®) HIV combi PT assay is a fourth-generation antigen-antibody combination assay developed to allow earlier detection of seroconversion, and to have increased sensitivity and improved specificity. We aimed to determine how early the assay could detect infection compared with existing assays; whether all HIV variants could be detected; and the assay's specificity using samples from blood donors, routine specimens, and patients with potential cross-reacting factors. Samples were identified as positive by the Elecsys(®) assay 4.9 days after a positive polymerase chain reaction result (as determined by the panel supplier), which was earlier than the 5.3-7.1 days observed with comparators. The analytical sensitivity of the Elecsys(®) HIV combi PT assay for the HIV-1 p24 antigen was 1.05 IU/mL, which compares favorably with the comparator assays. In addition, the Elecsys(®) assay identified all screened HIV subtypes and displayed greater sensitivity to HIV-2 homologous antigen and antibodies to HIV-1 E and O and HIV-2 than the other assays. Overall, the specificity of the Elecsys(®) assay was 99.88 % using samples from blood donors and 99.81 % when analyzing unselected samples. Potential cross-reacting factors did not interfere with assay performance. The Elecsys(®) HIV combi PT assay is a sensitive and specific assay that has been granted the CE mark according to Directive 2009/886/EC.

Adjunctive effect of chlorhexidine antiseptics in mechanical periodontal treatment: first results of a preliminary case series.

OBJECTIVES: The aim of the present case series was to evaluate the clinical and microbiological effects of a single session of mechanical and manual scaling and root planing (SRP) combined with the use of two different chlorhexidine formulations in the treatment for generalized chronic periodontitis. METHODS: Ten patients affected by chronic periodontal disease with periodontal probing depth (PPD) ≥ 5 mm were treated with SRP plus local chlorhexidine. In each patient, similar teeth, treated with SRP with the adjunctive use of chlorhexidine digluconate and dihydrochloride or chlorhexidine gluconate, respectively, were selected and assigned to a test and a control group. In both groups, PPD, bleeding on probing (BOP) parameters, total bacterial counts (TBC) and quality of periodontal bacteria at time 0 and 6 weeks after treatment were measured. RESULTS: PPD significantly decreased over time both in the test and in the control group; however, no significant differences between the two groups were observed. BOP and TBC were significantly lower in the test than in the control group 6 weeks after treatment. In the post-treatment revaluation, a significant decrease both in the treatment and in the control group, for each of the single periodontal pathogens, was observed. CONCLUSION: In this study--a preliminary case series with small sample size and short follow-up--the adjunctive use of chlorhexidine (CHX) to SRP resulted in clinical and microbiological benefits in the treatment for generalized chronic periodontitis. A CHX gel formulation consisting of CHX digluconate and CHX dihydrochloride seems to lead some additional benefits over SRP plus CHX gluconate in the short term. Additional investigations are needed to evaluate the effectiveness of this antiseptic therapy.

Positive and negative regulation of cellular immune responses in physiologic conditions and diseases.

The immune system has evolved to allow robust responses against pathogens while avoiding autoimmunity. This is notably enabled by stimulatory and inhibitory signals which contribute to the regulation of immune responses. In the presence of a pathogen, a specific and effective immune response must be induced and this leads to antigen-specific T-cell proliferation, cytokines production, and induction of T-cell differentiation toward an effector phenotype. After clearance or control of the pathogen, the effector immune response must be terminated in order to avoid tissue damage and chronic inflammation and this process involves coinhibitory molecules. When the immune system fails to eliminate or control the pathogen, continuous stimulation of T cells prevents the full contraction and leads to the functional exhaustion of effector T cells. Several evidences both in vitro and in vivo suggest that this anergic state can be reverted by blocking the interactions between coinhibitory molecules and their ligands. The potential to revert exhausted or inactivated T-cell responses following selective blocking of their function made these markers interesting targets for therapeutic interventions in patients with persistent viral infections or cancer.

High specificity of line-immunoassay based algorithms for recent HIV-1 infection independent of viral subtype and stage of disease.

BACKGROUND: Serologic testing algorithms for recent HIV seroconversion (STARHS) provide important information for HIV surveillance. We have shown that a patient's antibody reaction in a confirmatory line immunoassay (INNO-LIA HIV I/II Score, Innogenetics) provides information on the duration of infection. Here, we sought to further investigate the diagnostic specificity of various Inno-Lia algorithms and to identify factors affecting it. METHODS: Plasma samples of 714 selected patients of the Swiss HIV Cohort Study infected for longer than 12 months and representing all viral clades and stages of chronic HIV-1 infection were tested blindly by Inno-Lia and classified as either incident (up to 12 m) or older infection by 24 different algorithms. Of the total, 524 patients received HAART, 308 had HIV-1 RNA below 50 copies/mL, and 620 were infected by a HIV-1 non-B clade. Using logistic regression analysis we evaluated factors that might affect the specificity of these algorithms. RESULTS: HIV-1 RNA < 50 copies/mL was associated with significantly lower reactivity to all five HIV-1 antigens of the Inno-Lia and impaired specificity of most algorithms. Among 412 patients either untreated or with HIV-1 RNA ≥ 50 copies/mL despite HAART, the median specificity of the algorithms was 96.5% (range 92.0-100%). The only factor that significantly promoted false-incident results in this group was age, with false-incident results increasing by a few percent per additional year. HIV-1 clade, HIV-1 RNA, CD4 percentage, sex, disease stage, and testing modalities exhibited no significance. Results were similar among 190 untreated patients. CONCLUSIONS: The specificity of most Inno-Lia algorithms was high and not affected by HIV-1 variability, advanced disease and other factors promoting false-recent results in other STARHS. Specificity should be good in any group of untreated HIV-1 patients.