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We aimed at evaluating extension listing under UNOS status 1 (VA ECMO) and 2 (IABP and percutaneous endovascular device (PED)) with temporary devices. The UNOS thoracic transplant database for adult patients (Age>17years) listed after October 2018 was queried to identify patients listed as status 1 or 2 at anytime during their waiting period. Patients listed with temporary device receiving extension were identified and their waiting list outcomes were evaluated. A total of 15112 patients were listed since October 2018 of which 6533 (43%) were listed as status 2 and 1376 (9%) as status 1 at anytime during their waiting period. Of the status 2 patients 59% had IABP, 15% had PED. Of the status 1 patients, 64% had VAECMO. At least one extension was allowed for 11% VAECMO, 24% IABP and 30% PED patients. The median waiting list duration for extension patients was significantly higher (Table 1). Higher creatinine, Non-ischemic cardiomyopathy and blood group O were major factors associated with extension of status (Table 1). 25% VAECMO, 15% IABP and 12% PED patients downgraded their status to 3 or below. Figure 2 shows waiting list outcomes status 1 and 2 patients with temporary devices. 8% ECMO, 5% IABP and 5% PED patients coverted a durable VAD beyond their allowed period. Irrespective of guidelines, new UNOS heart allocation system allows temporary device patients extension in higher listing statutes and is commonly used by programs and is associated blood group, kidney function and etiology. The temporary device extensions should be re-evaluated by the UNOS committee with more objective criteria for adherence. [ABSTRACT FROM AUTHOR]

The United Network for Organ Sharing (UNOS) updated the heart transplant (HTx) allocation system in 2018, which led to significant changes in listing strategy and waitlist outcomes. Clinical predictors of post-transplant mortality since the allocation system change have not been well characterized. The UNOS database from October 2018 to June 2022 was queried for adult patients listed for HTx (n=11489). The dataset was divided in a test cohort (n=6872, 60%) and validation cohort (n=4617, 40%). A Cox Regression analysis was performed on the test cohort to identify risk-factors for adverse post HTx survival. Based on the risk-factors, a score (max 16) was developed to classify patients in the validation cohort into risk groups of Low (<2), Mid (2-4), High (5-7) and Very High (8+). The post-transplant survival was evaluated in the validation stratified by the risk groups. In the test cohort the higher age, female sex, recipient blood group O, etiology of heart failure, BMI, mean PA pressure, Creatinine, Bilirubin, listing with a durable LVAD, or listing on ECMO or ventilator were associated with higher post-transplant mortality (Table 1, also shows HR based risk score for individual variables). The total risk profile was associated with increased risk of post-transplant mortality. 1-year survival for low, mid, high and very high risk group was 95%, 91%, 82% and 66%, respectively (Figure 1). Easily obtainable clinical characteristics at time of heart transplant can predict post-transplant outcomes in the current era. The new risk score highlights the expected one year survival at time of transplant, and uses common clinical variables. [ABSTRACT FROM AUTHOR]

The UNOS heart transplant policy was changed in October 2018 giving priority to temporary mechanical support devices (tMCS). The primary aim of the study was to evaluate the distribution of patients listed and transplanted based on new priority status and their waitlist and post-transplant outcome. The UNOS thoracic transplant data was queried after October 2018 to identify adult patients listed for heart transplant (n=10957) based on their UNOS priority status. The 30-day transplant rate based on listing status was evaluated. Kaplan Meier curves were used for post-transplant survival stratified by the transplant UNOS status (1, 2, 3, 4). The initial listing status 1, 2, 3, 4, 5 and 6 was in 511 (6%), 2296 (21%), 1242 (11%), 4098 (37%), 316 (3%) and 2352 (22%) patients respectively. 142 (1%) patients at listing and 1359 (12%) after listing became inactive. Of all transplants (n=7025), 50% (n=3505) had end priority status 2, half (48%) of which were upgraded from lower statuses (Status 4=21%). Over 75% Status 1 and 2 patients are transplanted in 30 days of listing (Figure 1). 33% in status 4 and 47% status 6 are upgraded to prior to transplant. Status 1 patients had worst port transplant survival at 1 year (82% v. 91% v. 87% v. 90%, p<.01) compared to statuses 2, 3, 4 (Figure 2). Over 60% of patients listed for heart transplant under new UNOS policy are Status 4, 5 or 6 whereas more than 50% of patients transplanted are Status 1 and 2. Over 33% patients from status 4 and 6 are upgraded to higher statuses before transplant. Status 1 and 2 patients have higher rate of transplant within 30 days of listing. Status 1 patients have worst post-transplant survival. [ABSTRACT FROM AUTHOR]

The new United Network for Organ Sharing (UNOS) policy has resulted in significantly higher number of temporary mechanical support device use including IMPELLA due to provision of higher priority with its use while on waitlist. We aimed to identify temporal changes in IMPELLA use and its outcomes in patients awaiting heart transplant (HTx). The UNOS thoracic organ transplant database was queried between years 2015 and 2019 for patients aged >17 years, listed to undergo HTx. The available dataset was stratified in 2 groups based on implementation of UNOS policy (Oct 18, 2018); new and old era. Basic descriptive statistics were used to analyze the data. A total of 378 patients had IMPELLA awaiting HTx. The IMPELLA use skyrocketed from 2015 (1%) to 2019 (4%, Cochran-Armitage p <0.01, Figure 1A). The risk profile of IMPELLA patients before and after the policy change in terms of listing age, PA pressure, creatinine and heart failure etiology were comparable.. More patients with IMPELLA directly transplanted (81% vs. 56%, p<.01), had lower waiting time (median 12 vs. 45 days, p<.01), waitlist mortality (24% vs. 12%, p<.01), and converted to a durable support (13% vs. 5%) after policy change (Figure 1B). The IMPELLA use as a temporary support device for bridge to HTx has significantly increased after UNOS policy change. This increase has resulted in more patients transplanted while supported by Impella on waiting list. This increase in IMPELLA use shows a substantial change in practice patterns of listing and managing patients on the HTx waitlist. [ABSTRACT FROM AUTHOR]

Abstract: Intentional islanding of a power system can be an emergency response for isolating failures that might propagate and lead to major disturbances. Some of the islanding techniques suggested previously do not consider the power flow model; others are designed to minimize load shedding only within the islands. Often these techniques are computationally expensive. We aim to find approaches to partition power grids into islands to minimize the load shedding not only in the region where the failures start, but also in the topological complement of the region. We propose a new constraint programming formulation for optimal islanding in power grid networks. This technique works efficiently for small networks but becomes expensive as size increases. To address the scalability problem, we propose two grid partitioning methods based on modularity, properly modified to take into account the power flow model. They are modifications of the Fast Greedy algorithm and the Bloom algorithm, and are polynomial in running time. We tested these methods on the available IEEE test systems. The Bloom type method is faster than the Fast Greedy type, and can potentially provide results in networks with thousands of nodes. Our methods provide solutions which retain at least 40–50% of the system load. Overall, our methods efficiently balance load shedding and scalability. [Copyright &y& Elsevier]

Load shedding has always been a commonly adopted method in emergency situations to maintain power system reliability. Several load-reduction strategies have been suggested in the past, but most are complex and not scalable. This article proposes and thoroughly investigates three load-shedding strategies to prevent cascading failures in the power grid. The first strategy is a baseline case called the homogeneous load-shedding strategy. It homogeneously reduces load in all of the buses of the system. This strategy is extremely simple and fast, and these properties motivate its use in some specific scenarios in spite of its inefficiencies. Next, to accurately find the location and amount of load shedding, a polynomial complexity optimization formulation is proposed, which is much more efficient in overall load shedding in the system. A novel tree heuristic is proposed to overcome the drawbacks of the optimization, namely fairness and scalability. The tree heuristic is linear and very simple to implement. In general, it gives close to optimal results. The results of the tree strategy are compared with that of another existing heuristic, and it is found that the tree performs equal to or better than the existing heuristic for all cases. [ABSTRACT FROM AUTHOR]

Induction of mucosal immunity is critical for protection from enteric pathogens. Heat shock protein gp96 is one of the primary peptide and protein chaperones located in the endoplasmic reticulum. We reported previously that a cell-secreted gp96-Ig fusion protein (gp96-Ig) mediated strong systemic, antigen-specific CD8-CTL expansion in vivo. We now evaluate the mucosal immune response to stimulation by secreted gp96 using allogeneic NIH-3T3 transfected with ovalbumin (OVA) and gp96-Ig. A single intraperitoneal NIH-3T3-OVA-gp96-Ig immunization caused significant homing of OVA-specific TCR transgenic CD8 cells (OT-I) to Peyer's patches, to the intraepithelial compartment and to the lamina propria. Intraperitoneal immunization with cells secreting gp96-Ig provided stronger mucosal immunity than the same dose instilled vaginally or rectally or injected subcutaneously or intradermally. Our results provide the first evidence that cell-based gp96-Ig-secreting vaccines may serve as a potent modality to induce mucosal immunity. [ABSTRACT FROM AUTHOR]

The use of temporary mechanical circulatory support, IABP and Impella, for UNOS Status 2 patients has increased since the new policy implementation. The aim of the study was to evaluate overall listing transplant trends and outcomes of status 2 patients We evaluated the UNOS database from October 2018 to March 2021 for adult heart patients listed (n=10957) and transplanted (n=7025) based on their priority status. We analyzed the characteristics and outcomes of patients listed under Status 2 classifying them in two groups: with IABP or percutaneous mechanical circulatory support (pMCS) using descriptive, univariate and survival statistics During the study period 3687 patients were listed (3505 (95%) transplanted) as Status 2 of which 1823 (52%) were original Status 2 while the remainder (1682, 48%) were upgraded (21% status 4). Of Status 2 patients, 2033 (55%) had IABP and 423 (11%) had pMCS. The median age (57 v. 57) and BMI (26 v. 27) were comparable between the groups. The IABP patients had higher cardiac index (1.64 v. 1.6, p=0.08) and albumin (3.6 v. 3.2, p<.01), lower creatinine (1.2 v. 1.3, p<.01) and bilirubin (0.9 v. 1.1, p<.01) at time of device placement. Patients with pMCS were more likely male (87% v. 75%, p<.01) and on inotropes (82% v. 72%, p<.01) with dobutamine (28% v. 36%, p<.01) and epinephrine (2% v. 15%, p<.01). The 14 day transplant rate was better in IABP group (80% v. 73%) while post-transplant survival was comparable at 1 year (92% v. 88%, p=0.09). 72% of all IABPs were placed at IABP predominant centers (>80% Status 2 devices IABP) while 15% pMCS were implanted at pMCS predominant centers (p<.01) Since the new policy, 50% of all transplants are performed with UNOS Status 2 of which 48% are after being upgraded and 66% have either an IABP or pMCS. Compared to IABP, patients requiring pMCS are more likely to be male, with end-organ dysfunction and higher requirement of inotropes which could be useful in choosing appropriate device. Center level variation exist in type of device used in favor of IABP [ABSTRACT FROM AUTHOR]

OBJECTIVE: In this study, we tested the hypothesis that the CD4(+)/CD8(+) T cell ratio could predict HIV infection status in HIV-exposed infants. METHODS: CD4(+)/CD8(+) T cell ratios were determined from data for live-born singleton infants who had been prospectively enrolled in the Women and Infants Transmission Study. Data for 2208 infants with known HIV infection status (179 HIV-infected and 2029 uninfected infants) were analyzed. RESULTS: Receiver operating characteristic curves indicated that the CD4(+)/CD8(+) T cell ratio performed better than the proportion of CD4(+) T cells for diagnosis of HIV infection as early as 2 months of age, and this relationship was unaffected by adjustment for maternal race/ethnicity, infant birth weight, gestational age, and gender. At 4 months of age, 90% specificity for HIV diagnosis was associated with 60% sensitivity. For ease of use, graphical estimates based on cubic splines for the time-dependent parameters in a Box-Cox transformation (L), the median (M), and the coefficient of variation (S) were used to create LMS centile curves to show the sensitivity and specificity of CD4(+)/CD8(+) T cell ratios in HIV-infected and uninfected infants until 12 months of age. At 6 months of age, a simplified equation that incorporated sequential CD4(+)/CD8(+) T cell ratios and hematocrit values resulted in improved receiver operating characteristic curves, with 94% positive predictive value and 98% negative predictive value. The positive and negative predictive values remained above 90% in simulated infant populations over a wide range of HIV infection prevalence values. CONCLUSIONS: In the absence of virological diagnosis, a presumptive diagnosis of HIV infection status can be made on the basis of CD4(+)/CD8(+) T cell ratios in HIV-1-exposed infants after 2 months of age; sensitivity and specificity can be improved at 6 months by using a discriminant analysis equation. [ABSTRACT FROM AUTHOR]

Landmark work has demonstrated that the hemocompatibility-related adverse event (HRAE) burden is significantly lower with the newest centrifugal flow pump; however, no study has specifically examined this HRAE burden on the prior commercially available pumps and the impact on functional outcomes. We performed a retrospective analysis of HRAE (non-surgical bleeding, thrombo-embolic event, pump thrombosis, or neurological event) burden in patients following surgical implantation of Heart-Mate II (HMII) or Heart-Ware (HW) devices through 1 year of clinical follow-up. An HRAE were categorized by the type and severity of an adverse event and then assigned a net Hemocompatibility Score (HCS) of 0 through 4 for no HRAE through life-ending or disabling HRAE. Statistical analysis included comparison of net HCS using proportional regression, as well as impact on functional outcomes [NYHA class, dyspnea score, 6-minute walk, and peak venous oxygen consumption (VO 2)] The study cohort included a total of 331 patients, with 268 patients (81%) in the HMII group and 63 patients (19%) in HW group. The overall median age was 62.2 years; patients receiving HMII were older (median 63.5 versus 58.1years, p<0.001). Net HCS per patient in the HMII group was 0.7 (±1.4), reported as mean (± standard deviation). This was similar to the net HCS per patient of 0.5 (±1.2) in the HW group (p=0.36). A scatter-plot analysis demonstrates no significant impact on functional outcomes between the comparison groups for NYHA class (p=0.06), 6-minute walk distance (p=0.54), Borg dyspnea rating (p=0.12) or peak VO 2 (p=0.83) (Figure 1). Burden of HRAE does not adversely affect measures of functional capacity after device implantation. Furthermore, this did not differ with the use of prior commercially-available devices. These findings indicate that overall functional quality of life may not be significantly impacted by burden of HRAE regardless of pump technology. [ABSTRACT FROM AUTHOR]

To investigate the role that DC-SIGN neck-region length variation plays in HIV-1 transmission, we studied 530 HIV-1-positive and 341 HIV-1-negative individuals in China. The carrier frequency of a DC-SIGN allele with <5 repeat units in the neck-region was 0.9% in HIV-1-positive and 3.8% in HIV-1-negative individuals (P=.007), an observation suggesting that this DC-SIGN variation plays a role in HIV-1 transmission. These naturally occurring DC-SIGN neck-region variants were significantly more frequent in the Chinese population than in the US population (P <.001) and in a worldwide population (P=.006). [ABSTRACT FROM AUTHOR]

Gastrointestinal bleeding (GIB) is a frequent post left ventricular assist device (LVAD) co-morbidity, and many patients require multiple endoscopic interventions. While GI bleeding events have been shown to impact subsequent outcomes, the association of the burden of GI bleeding interventions with subsequent outcomes has not been specifically analyzed. Between February 2007 and June 2019, 389 patients underwent primary LVAD implantation at our Clinic. Median age at implant was 62 years (range, 18-82 years) and 306 (79%) were male. Etiology of heart failure was ischemic in 182 patients (47%) and indication for implant was destination therapy in 266 (69%). Axial flow pump was utilized in 282 (73%) and centrifugal flow in 105 (27%). Median preoperative duration of heart failure was 8.9 years. Early mortality occurred in 27/387 patients (7%). Follow-up was available in all 350 early survivors for a median of 1.8 years (920 years of patient support). There were 462 GI bleeding events in the 350 early survivors during the follow up time period. During these 462 bleeding events, endoscopic procedures were performed in 341/462 instances (74%) and intervention was performed in 96/341 (28%). Figure 1 shows the relative hazard of outcomes as related to burden of GI interventions for bleeding; late survival (p=0.95) and thrombotic complications (p=0.69) were not significantly impacted by increasing number of required GI interventions. However, risk of subsequent stroke (p=0.04) was significantly increased with higher number of procedures required. GI bleeding events are common after LVAD implant and endoscopic interventions are often required. Anticoagulation cessation is often required during these instances, and subsequent risk of stroke may be increased as the number of these procedures required is increased. Careful attention to peri-procedural anticoagulation and management may be critical to reduce subsequent unintended adverse events. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cytokines are important for inducing T cell maturation, proliferation, and survival. Despite the known dysregulation of cytokines in human immunodeficiency virus (HIV) infection, cytokine receptor expression is relatively unexplored. METHODS: We examined maturation markers (naive, central memory, effector memory, and effector); the cytokine receptors interleukin (IL)-2R beta, common gamma (C gamma) chain, IL-7R alpha, IL-15R alpha; and proliferative responses of T cells in a cohort of HIV-infected pediatric patients (median age, 14.82 years) receiving antiretroviral therapy, arbitrarily designated as immunologic responders (group I) and nonresponders (group II) on the basis of a CD4+ T cell count cutoff of 25%. RESULTS: Patients had increased percentages of effector memory CD8+ T cells, in comparison with those in healthy control subjects, with reduced expression of IL-7R alpha in the central memory and effector memory subsets and of the C gamma chain in all maturation subsets of CD8+ T cells. IL-7R alpha +CD8+ T cell percentages were directly correlated with CD4+ T cell percentages. In immunologic nonresponders, anti-CD3+ or HIV Gag antigen-induced CD8+ T cell proliferation was impaired, but proliferation in response to the homeostatic cytokines IL-2 and IL-15 was preserved. Conclusions. Cytokine receptor deficiencies may contribute to immune deficiency in HIV-infected patients, and gamma-chain-utilizing cytokines may play an important role in vivo in maintaining the memory subsets of T cells in patients with CD4+ T cell deficiency. Copyright © 2006 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

The novel early activation antigen, EA1, has been shown to be induced by mitogens, antigens and the tumour promoter, phorbol myristate acetate (PMA), on human lymphocytes. This antigen has been designated to be CD69, EA1 has also been shown to be expressed on thymocytes without exogenous activation stimuli. In order to characterize further the expression of EA1 on thymocytes, the ontogeny of its expression was studied. EA1 appeared between 7 and 9.5 weeks of gestation, after colonization of the thymic rudiment with CD7+ T cell precursors, but before the onset of compartmentalization of the thymus into cortical and medullary zones. After cortico-medullary differentiation, the majority of medullary thymocytes expressed EA1 while only a fraction of the cortical thymocytes expressed this antigen. In the fetal and post-natal cortex. EA1 expression appeared to cluster in the subcapsular cortex. EA1+ cells were also scattered throughout the inner cortex. By two-colour fluorocytometric analysis of post-natal thymocytes, it was shown that EA1 was expressed on 30 to 65% of thymocytes. EA1 was expressed on CD4+ CD8+ as well as on the more immature CD4- CD8- thymocytes. In contrast to circulating T cells, thymocytes were much less responsive to PMA stimulation for the expression of EA1. Molecular characterization showed that EA1 on thymocytes had the same structure as that of activated peripheral T cells. In addition, thymic EA1 was constitutively phosphorylated. Thus, EA1 expression is acquired early during thymic development after colonization of the thymic rudiment by CD7+ T cell precursors. However, the specific role that EA1 may play in the activation and function of developing thymocytes remains to be determined. [ABSTRACT FROM AUTHOR]

We have developed CD4+, tetanus antigen-specific T cell clones that proliferate in the presence of tetanus antigen and autologous irradiated peripheral blood leucocytes (PBL) as antigen-presenting cells (APC). There have been several reports that T cells can present antigen themselves. We have used tetanus antigen-specific T cell clones to examine the effects of envelope glycoproteins of HIV-1 on processing and presentation of antigen to T cells. Cloned T cells were pre-incubated with soluble crude preparation of tetanus antigen for 4 h at 37 °C, irradiated, and used as APC (T-APC). These cells could present antigen, as assessed by the ability of the autologous cloned T cells to proliferate. Resting T cells and phytohaemagglutinin-activated T cell blasts from autologous PBL could not present tetanus antigen to the responder cloned T cells. Antigen presentation by T-APC was abrogated by treating cells with anti-HLA-DR but not by anti-HLA-DQ monoclonal antibodies; treatment of tetanus antigen-pulsed T-APC with anti-tetanus antibody also blocked the ability of these cells to induce proliferation in responder T cells. Antigen presentation by cloned T cells was by a chloroquine-resistant pathway. Pretreatment of T-APC with envelope glycoprotein of HIV-1, gp 120, did not affect the proliferalive responses of the responder T cells. These data suggest that gp 120 does not inhibit the antigen-presenting function while suppressing antigen-specific responses. [ABSTRACT FROM AUTHOR]

Two intravenous drug users dually infected with human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type II (HTLV-II) developed an unusual severe dermatitis characterized by progressive brawny induration, fissuring, and ulceration of the skin, with an associated CD8 cell infiltration in one patient. Both patients had persistent eosinophilia. Lymph node biopsy revealed dermatopathic lymphadenopathy, an unusual pathologic finding in HIV-1 infection but one seen in association with mycosis fungoides and other skin disorders. Two new isolates of HTLV-II virus were established from these patients and were identified as HTLV-II by Southern blotting. This type of skin disease and lymph node pathology has not been found in other intravenous drug users who have been infected with HIV-1 alone or in patients in other risk groups for HIV-1 infection. HTLV-II may play a role in this unique new disease pattern in patients infected with HIV-1. [ABSTRACT FROM AUTHOR]

Context: Pediatric human immunodeficiency virus (HIV) infection has unique viral pathogenetic features that preclude routine extrapolation from adult studies and require specific analysis.Objectives: To evaluate the prognostic value of 2 key laboratory markers-plasma RNA and CD4+ lymphocyte count-for HIV disease progression in infants and children and to establish targeted values for optimal outcome.Design: Data from a cohort of 566 infants and children who participated in a randomized, placebo-controlled trial of nucleoside reverse transcriptase inhibitors (ACTG 152) were analyzed. The trial was conducted between 1991 and 1995 and enrolled a heterogeneous cohort of antiretroviral therapy-naive children (age, 3 months to 18 years); patients had a median follow-up of 32 months.Main Outcome Measures: The trial clinical end points consisted of time to first HIV disease progression (growth failure, decline in neurologic or neurodevelopmental function, opportunistic infections) or death.Results: Baseline plasma RNA levels were high (age group medians, 5 x 10(4) to >10(6) copies/mL), and both baseline RNA and CD4+ lymphocyte count were independently predictive of subsequent clinical course. Risk reduction for disease progression between 49% and 64% was observed for each log10 reduction in baseline RNA and was linear without suggestion of a threshold or age effect. Disease progression predictive power was enhanced by the combined use of plasma RNA and CD4+ cell count. Marker values of less than 10000 copies/mL for plasma RNA and greater than 500 x 10(6)/L (<6.5 years of age) or greater than 200 x 10(6)/L (>6.5 years) for CD4+ cell count were associated with a 2-year disease progression rate of less than 5%.Conclusions: Two key laboratory markers--plasma RNA and CD4+ lymphocyte count-are independent predictors of clinical course among HIV-infected infants and children. The linear, age-independent relationship between log10 plasma RNA and relative risk of disease progression strongly supports therapeutic efforts to achieve plasma virus levels as low as possible. [ABSTRACT FROM AUTHOR]

Background: During HIV infection, apart from use of PI-based regimen, low CD4+ T-cell count has also been identified as a vascular risk factor. Initiating ART in patients with higher nadir CD4 counts is speculated to better normalise CVD risks and inflammatory response. We aimed to study effect of nadir CD4 count on CVD and inflammatory response in ART naive and treated HIV patients. Methods & Materials: Cross-sectional enrolment of 169 HIV-infected patients (68 naive; 101 ART experienced) with different nadir CD4 counts; Drug Naive(DN)- Group 1 (n=24;Nadir CD4<350cells/µL); Group2 (n=44;Nadir CD4>350cells/µL); ART experienced- Group 3 (n=32;Nadir CD4 <200cells/µL);Group 4 (n=36;Nadir CD4 200-350cells/µL);Group 5 (n=33;Nadir CD4 >350cells/µL) and Group 6 (n=29 healthy controls (HC) were done. Wemeasured serum lipid profile (LP), C-IMT, cardiac output, TNFR- 1, TNFR-2 for inflammation, sCD14 for microbial translocation (MT) by ELISA. Descriptive statistics were used for demographics; ANOVA to identify differences in LP, C-IMT, cardiac output, inflammation, MT between groups. Results: Mean age, median current and nadir CD4 count for groups 1-5: 37.7±5.6, 123.5(70-273.5), 123.5(70-273.5); 35.36±5.2, 534(440-595), 572(496.5-761.25); 38.7±5.7, 138.5(83- 167.5), 569(430.25-773.5); 38.3±5.9, 273.5(228.5-317.5), 717(564- 867.5); 40.3±5.1, 402(378-438), 777(649-1005); 37±5.9. C-IMT (p<0.05), TC, TG, TNFR-2, sCD14 (p<0.05) increased in DN and ART than HC. Cardiac output (p<0.001) decreased, TNFR-1 (p=NS), TNFR- 2 (p<0.001), sCD14 (p<0.001) higher in DN than ART. No significant difference in C-IMT between groups based on nadir CD4 counts. In naive patients, increased cardiac output (p<0.001), decreased TNFR-1 (p<0.001), TNFR-2 (p<0.001) and sCD14 (p<0.001) was seen in group 2 than group 1. We did not identify statistically significant difference in LP, cardiac output, TNFR-1, TNFR-2, sCD14 levels between groups 3-5. We identified significant correlation (p<0.05) between low CD4 count and increase in C-IMT on ART patients. Conclusion: From clinical perspective, no significant betterment in terms of decrease in inflammatory response, C-IMT and increase in cardiac output was identified during early initiation of ART. However, we found significant increase in inflammatory and MT markers in naive patients with nadir CD4 <350 cells/µL than those with higher nadir CD4 count. [ABSTRACT FROM AUTHOR]

The use of stimulants such as methamphetamine may accelerate HIV disease progression, but scant research has examined stimulant-associated pathophysiologic alterations in treated HIV. In a sample of 55 HIV-positive, methamphetamine-using sexual minority men with a viral load less than 200 copies/mL, 27 participants with a urine sample that was reactive for recent stimulant use (Stimulant Tox+) were compared to 28 who tested negative in urine for stimulants (Stimulant Tox−). Analyses employed the false discovery rate (FDR) under the Benjamini-Hochberg procedure with a 10% cut-off. Stimulant Tox+ participants did not differ from those who were Stimulant Tox− on demographic and clinical characteristics. However, Stimulant Tox+ participants reported more days using methamphetamine in the past 30 days (10.7 versus 4.0; p < 0.01). RNA sequencing provided evidence for differential expression of 32 genes and perturbation of 168 pathways in recent stimulant users. Most notably, we observe upregulation single genes linked to HIV latency (i.e., CD274 and FCGR2A) in Stimulant Tox+ participants. Pathway analyses indicated that recent stimulant use was associated with two-directional perturbation of gene sets governing HIV latency, immune activation, inflammation, neuroendocrine hormone regulation, and neurotransmitter synthesis. Stimulant Tox+ participants also displayed significantly higher log 10 TNF-alpha plasma levels (Mean = 1.74 versus 1.63; p = 0.023). Further research is needed to examine these mechanisms whereby stimulant use may contribute to HIV persistence and disease progression. [ABSTRACT FROM AUTHOR]

An abstract of the research paper "Peripheral T follicular helper cells from H1N1/09 vaccine nonresponders fail to induce antigen-specific antibody production in vitro," by A. Parmigiani and colleagues is presented.

An abstract of the conference paper "Recombinant IL-21 induces perforin and granzyme B in total and virus specific CD8 Tcells in acute and early stages of SIV infection in rhesus macaques" by S. Pallikkuth and colleagues is presented.