The Optimal Cutoff Value to Predict HIV Infection Using the Architect HIV Ag/Ab Combo.

BACKGROUND: The Architect HIV Ag/Ab Combo has been implemented worldwide as a screening test for more than ten years. However, its high sensitivity may lead to false-positive results in a low-prevalence setting. METHODS: This study was carried out to evaluate the performance of the Architect HIV Ag/Ab Combo based on the sample-to-cutoff (S/CO) ratios, to explore the optimal cutoff value to predict HIV infection and reduce the frequency of false-positive results. A retrospective analysis of clinical samples using the Architect HIV Ag/Ab Combo between July 2011 and February 2020 was performed. The sensitivity, specificity, positive predictive value (PPV), and false-positive rate (FPR) were evaluated and the receiver operating characteristic curve (ROC) analysis was used to determine the optimal cutoff value to predict HIV infection. RESULTS: During the study period, 531 out of 692,155 samples were repeatedly reactive by the Architect HIV Ag/Ab Combo. The median S/CO value of HIV-positive were significantly higher than that of false-positive. The PPV of males (85.68%) was significantly higher than that of females (47.89%). The optimal cutoff value estimated by ROC analysis was 8.96 with the highest sum of sensitivity (100.00%) and specificity (100.00%) for males. However, for females, the optimal cutoff value was 26.97 with the highest sum of sensitivity (100.00%) and specificity (100.00%). CONCLUSIONS: For the Architect HIV Ag/Ab Combo, the optimal cutoff value needs to be set for the different genders to predict the final status of HIV infection reliably.

Dexamethasone impairs the differentiation and maturation of murine dendritic cells by Toll-like receptor 4-nuclear factor-kappaB pathway.

BACKGROUND: Recent studies have demonstrated that dexamethasone (DEX) interferes with immune responses by targeting key functions of dendritic cells (DCs) at the earliest stage. However, the cellular and molecular mechanisms are still incompletely understood. This study aimed to explore the possible mechanisms by investigating the roles of DEX on differentiation, maturation & function of murine DCs and the effects of DEX on DCs via Toll-like receptor 4 (TLR4)-nuclear factor (NF)-kappaB mediated signal pathway. METHODS: Immature DCs (imDCs) were cultured from murine bone marrow (BM) cells. We added DEX into culture medium at different time. The expression of CD11c, CD86 and I-A(b) (mouse MHC class II molecule) was determined by flow cytometry. We determined the expression of NF-kappaB and its inhibitory protein I-kappaBalpha by electrophoretic mobility shift assay (EMSA) and Western blotting, respectively. The productions of interleukin (IL)-12p70 and IL-10 in cell culture supernatants were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: DEX impaired differentiation of DCs from murine bone marrow progenitors, and inhibited lipopolysaccharide (LPS) induced maturation of DCs. DEX significantly inhibited NF-kappaB expression of normal DCs, the higher the DEX concentration or the longer the DEX treatment time, the more obvious the effect. However, DEX had little effect on LPS-induced NF-kappaB activation, and partially impaired LPS-induced I-kappaBalpha degradation. DEX significantly decreased LPS induced IL-12p70 production by DCs. Interestingly, our results showed a synergistic effect between DEX and LPS on the production of IL-10 by DCs. CONCLUSIONS: DEX inhibits the differentiation and maturation of murine DCs involved in TLR4-I-kappaB-NF-kappaB pathway, and also indirectly impairs Th1 development and interferes with the Th1-Th2 balance through IL-12 and/or IL-10 secretion by DCs.

Is circumferential pulmonary vein isolation preferable to stepwise segmental pulmonary vein isolation for patients with paroxysmal atrial fibrillation?

BACKGROUND: Stepwise segmental pulmonary vein isolation (SPVI) and circumferential pulmonary vein isolation (CPVI) have been developed to treat patients with atrial fibrillation (AF), but the preferable approach for paroxysmal AF (PAF) has not been established. METHODS AND RESULTS: One hundred and ten patients with symptomatic PAF were randomized into a stepwise SPVI group (n=55) or CPVI group (n=55). Systemic SPVI combined with left atrial linear ablation tailored by inducibility of AF was performed in the stepwise SPVI group. Circumferential linear ablation around the left and right-sided pulmonary veins (PVs) guided by 3-dimensional electroanatomic mapping was performed in the CPVI group. The endpoints of ablation are non-induciblity of AF in the stepwise SPVI group and continuity of circular lesions combined with PV isolation in the CPVI group. After the initial procedures, atrial tachyarrhythmis (ATa) recurred within the first 3 months in 23 of the 55 patients (41.8%) who underwent stepwise SPVI and in 20 of the 55 patients (36.4%) who had CPVI (p=0.69). Repeat procedures were performed in 7 patients from the stepwise SPVI group and 5 from the CPVI group (p=0.76). During the 3-9 months after the last procedure, 46 patients (83.6%) from the CPVI group and 43 (78.2%) from the stepwise SPVI group did not have symptomatic ATa while not taking anti-arrhythmic drugs (p=0.63). Severe subcutaneous hematoma or PV stenosis occurred in 3 patients. CONCLUSIONS: The efficacy of stepwise SPVI is comparable to that of CPVI for patients with PAF.

Achievement of pulmonary vein isolation in patients undergoing circumferential pulmonary vein ablation: a randomized comparison between two different isolation approaches.

INTRODUCTION: Circumferential pulmonary vein ablation (CPVA) with the endpoint of pulmonary vein (PV) isolation has been developed as an effective therapy for atrial fibrillation (AF). This endpoint can be achieved either by closing gaps along circular lines or by segmental PV isolation inside the circular lines after creation of initial CPVA lesions. We investigated whether the clinical outcome depends on the PV isolation approach used during the first-time CPVA procedure. METHODS AND RESULTS: One hundred consecutive patients (69 male; age, 56.7 +/- 11.6 years) who underwent first-time CPVA for treatment of symptomatic AF were enrolled. PV isolation was randomly achieved either by CPVA alone (aggressive CPVA [A-CPVA] group, n = 50) or by a combination of CPVA with segmental PV ostia ablation (modified CPVA [M-CPVA] group, n = 50). Recurrence of atrial tachyarrhythmias (ATa) within 3 months after the initial procedure occurred in 30 patients (60%) in the M-CPVA group and in only 15 patients (30%) in the A-CPVA group (P < 0.01). ATa relapse after the first 3 months was detected in 21 patients (42%) in the M-CPVA group, compared with 9 patients (18%) in the A-CPVA group (P = 0.01). At 13 +/- 4 months, patients treated by the A-CPVA approach had greater freedom from ATa recurrence than patients who underwent M-CPVA (P = 0.01). The M-CPVA approach was the only independent predictor associated with procedural failure (RR 0.318; 95% CI 0.123-0.821; P = 0.02). CONCLUSIONS: When PV isolation is the endpoint of CPVA, the efficacy of the A-CPVA approach is better than that of M-CPVA.