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Background: Previous studies identified gender disparities in surgical conference presenters and moderators. We sought to assess disparities in the representation of women in terms of speakers and moderators, but with particular emphasis on panels and topics of discussion at vascular surgery conferences. Methods: Data regarding presenters and moderators from the Southern Association of Vascular Surgery, Western Vascular Society, Vascular and Endovascular Surgical Society, Society for Clinical Vascular Surgery, and Society for Vascular Surgery conferences was obtained from online meeting archives and via email correspondence. Scientific session speakers, moderators, and panelists were identified by sex. Specific vascular topics for each discussion were also identified. Keynote speakers or special guests were excluded. Results: Compared to men, women were less often presenters (18% versus 82%, p <.002) and moderators (16% versus 84%, p <.001) of conference sessions. Women were most likely to present on dialysis access and least likely to present on venous disease overall. Women were more likely to present on aortic (24% vs 19%; p <.013) and cerebrovascular disease (33% vs 27%; p <.021) at regional compared to national conferences. Of panels assessed, 68% were all-male. Subgroup analysis suggests that some improvements have been made over time. Conclusions: Significant disparities persist in the topics presented and in panel composition suggesting potential areas for improvement in equity. Further study should focus on evaluating trends in the training level of the presenter and the topics presented, and assessing parity in structural factors that impact research presentation opportunities. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this narrative review is to provide the vascular surgery community with updated recommendations and information regarding the use of Targeted Muscle Reinnervation (TMR) for both the prevention and treatment of chronic pain and phantom limb pain occurring in patients after undergoing lower extremity amputation for peripheral artery disease. Methods: Current available literature discussing TMR is reviewed and included in the article in order to provide a succinct overview on the indications, clinical applications, and surgical technique for TMR. Additionally, early studies showing favorable long-term results after TMR are discussed. Patient consent for publication was obtained for this investigation. Results: TMR has been demonstrated to be an effective means of both treating and preventing neuroma-related symptoms including chronic pain and phantom limb pain. It has been proven to be technically feasible, and can help patients to have improved utilization of prostheses for ambulation, which can conceivably lead to a reduction in mortality. Conclusions: TMR is an important tool to consider for any patient undergoing lower extremity amputation for a vascular-related indication. A vascular-plastic surgeon dual team approach is an effective means to prevent and reduce neuromas and associated chronic pain in this patient population. [ABSTRACT FROM AUTHOR]

A WSe2 field effect transistor integrated with a lead zirconium titanate (PZT) pyroelectric device has been designed, fabricated, and tested and is described as the integrated pyroelectric device. The integrated device has been compared to a standalone pyroelectric device, which consists of PZT sandwiched between platinum electrodes. A pyroelectric coefficient of 1.755 × 10−4 C/m2K has been realized for our thin-film PZT (650 nm). The integrated device amplifies the output of the standalone device by over ten orders of magnitude as the current density calculated for the devices is 16 nA/mm2 and 1 nA/mm2, respectively. The interplay between the pyro- and ferro-induced polarization of the integrated device has been studied. From our observations, the ferroelectric gating controls directly the drain-source current output of the integrated device, showing anti-clockwise hysteresis behavior. The device shows promise for application in infrared sensing. [ABSTRACT FROM AUTHOR]

Objective: Renal impairment after repair of ruptured abdominal aortic aneurysm has been associated with post-operative mortality. Acute kidney injury (AKI) risk specifically related to contrast administration in endovascular aneurysm repair (EVAR) for intact vs ruptured aneurysms has not been previously described. It was our objective to evaluate the risk of AKI and the association with contrast administration in EVAR for ruptured (rEVAR) and intact (iEVAR) aneurysm repair in the Vascular Quality Initiative (VQI). Methods: Adult patients less than 90 years old undergoing EVAR in the VQI without prior abdominal aortic surgery or who were not actively on dialysis preoperatively were included. Patients immediately converted to an open repair were excluded. Patients were grouped by repair urgency, and patient and operative characteristics and outcomes compared. Univariable and multivariable analyses were performed to identify factors associated with the primary outcome of AKI. Survival was evaluated by Kaplan-Meier analysis. Results: Of 38,775 EVAR patients identified, 86.5% underwent elective surgery for an intact aneurysm, 8.4% had urgent surgery for a symptomatic, intact aneurysm, and 5.1% had emergent repair for a ruptured aneurysm. Significant risk factors for AKI included contrast volume, a preoperative eGFR <30 mL/min, procedure urgency, COPD, congestive heart failure (CHF), and total procedure time. The factor most associated with AKI was aneurysm rupture prior to repair (OR 8.6, CI 7.2-10.3, P <.01). The association of contrast volume with the outcome was the least strong with a 4% increase in risk per 25 mL of contrast (OR 1.04, 95% CI 1.01-1.07). With the development of AKI, postoperative survival was reduced regardless of indication. Conclusions: Of all factors assessed, aneurysm rupture was the most and contrast volume the least associated with AKI after EVAR. Further studies should evaluate methods of preventing post-EVAR AKI. [ABSTRACT FROM AUTHOR]

Objective: Aortic aneurysms and dissections are prevalent causes of morbidity and mortality. The management of aortic pathologies may be called into question in malpractice suits. Malpractice claims were analyzed to understand common reasons for litigation, medical specialties involved, patient injuries, and outcomes. Methods: Litigation cases in the Westlaw database from September 1st, 1987 to October 23 rd, 2019 were analyzed. Search terms included "aortic aneurysm" and "aortic dissection." Data on plaintiff, defendant, litigation claims, patient injuries, misdiagnoses, and case outcomes were collected and compared for aortic aneurysms, aortic dissections, and overall cases. Results: A total of 346 cases were identified, 196 involving aortic aneurysms and 150 aortic dissections. Physician defendants were emergency medicine (29%), cardiology (20%), internal medicine (14%), radiology (11%), cardiothoracic (10%) and vascular surgery (10%). Litigation claims included "failure to diagnose and treat" (61%), "delayed diagnosis and treatment" (21%), "post-operative complications after open repair" (10%) and "negligent post-operative care" (10%). Patients with aneurysms presented with abdominal (63%) and back pain (37%), while dissections presented with chest pain (78%), abdominal pain (15%), and shortness of breath (14%). Misdiagnoses included gastrointestinal (12%), other cardiovascular (9%), and musculoskeletal conditions (9%), but many were not specified (58%). Overall, 83% of cases were wrongful death suits. Injuries included loss of consortium (23%), emotional distress (19%), and bleeding (17%). In 53% of the cases, the jury ruled in favor of the defendant. 25% of cases ruled for the plaintiff. 22% of cases resulted in a settlement. The mean rewarded for each case was $1,644,590.66 (SD: $5,939,134.58; Range: $17,500-$68,035,462). Conclusion: For aortic pathologies, post-operative complications were not prominent among the reasons why suits were brought forth. This suggests improvements in education across all involved medical specialties may allow for improved diagnostic accuracy and efficient treatment, which could then translate to a decrease in associated litigation cases. [ABSTRACT FROM AUTHOR]

Background: In many facilities, the coronavirus disease (COVID-19) pandemic caused suspension of elective surgery. We therefore sought to determine the impact of this on the surgical experience of vascular trainees. Methods: Surgical case volume, breadth, and the participating trainee post-graduate level from 3 large New York City Hospitals with integrated residency and fellowship programs (Mount Sinai, Montefiore Medical Center/Albert Einstein College of Medicine, and New York University) were reviewed. Procedures performed between February 26 to March 25, 2020 (pre-pandemic month) and March 26 to April 25, 2020 (peak pandemic period) were compared to those performed during the same time period in 2019. The trainees from these programs were also sent surveys to evaluate their subjective experience during this time. Results: The total number of cases during the month leading into the peak pandemic period was 635 cases in 2019 and 560 cases in 2020 (12% decrease). During the peak pandemic period, case volume decreased from 445 in 2019 to 114 in 2020 (74% reduction). The highest volume procedures during the peak pandemic month in 2020 were amputations and peripheral cases for acute limb ischemia; during the 2019 period, the most common cases were therapeutic endovascular procedures. There was a decrease in case volume for vascular senior residents of 77% and vascular junior and midlevel residents of 75%. There was a 77% survey response rate with 50% of respondents in the senior years of training. Overall, 20% of respondents expressed concern about completing ACGME requirements due to the COVID-19 pandemic. Conclusions: Vascular surgery-specific clinical educational and operative experiences during redeployment efforts have been limited. Further efforts should be directed to quantify the impact on training and to evaluate the efficacy of training supplements such as teleconferences and simulation. [ABSTRACT FROM AUTHOR]

Objectives: While the use of protamine sulfate as a heparin reversal agent has been extensively reviewed in patients undergoing carotid endarterectomy and coronary artery bypass grafting, there is a lack of literature on protamine's effects on lower extremity bypasses. The purpose of this study was to determine the risk of protamine sulfate dosing after tibial bypass on thrombotic or bleeding events, including early bypass failure. Methods: We performed a retrospective review of our institutional database for patients undergoing primary distal peripheral bypass from January 2009 through December 2015 (contralateral bypass was considered to be a new primary bypass). Primary endpoints include composite thrombotic events (myocardial infarction, stroke, amputation at 30 days and patency less than 30 days) and composite bleeding events (bleeding or transfusion). Results: A total of 152 tibial or peroneal bypasses in 136 patients with critical limb ischemia were identified. Of these, 78 (57.4%) patients received protamine sulfate intraoperatively and 58 (42.6%) did not. There were no differences in composite thrombotic or hemorrhagic outcomes. Protamine use had no effect on the rates of perioperative MI (9.0% versus 3.5%, p = 0.20), stroke (1.3% versus 1.7%, p = 0.83), or perioperative mortality (5.1% versus 3.5%, p = 0.64). There was no significant difference in composite post-operative bleeding events (20.7% versus 14.1%, p = 0.31) or composite thrombotic events (17.2% versus 18.0%, p = 0.91). Patients who received protamine undergoing bypass with non-autogenous conduit had significantly higher-recorded median operative blood loss (250 mL versus 150 mL, p = 0.0097) and median procedure lengths (265 min versus 201 min, p = 0.0229). No difference in 30-day amputation-free survival was noted (91.0% versus 91.4%, p = 0.94). Follow-up Kaplan–Meier estimation did not demonstrate a difference in 30-day patency (91.7% versus 88.5%, p = 0.52). Conclusions: Heparin reversal with protamine sulfate after tibial or peroneal bypass grafting is not associated with higher cardiovascular morbidity, bypass thrombosis, amputation, or mortality. Additionally, there was no statistically significant difference in post-operative bleeding or thrombosis complications for patients who did not receive protamine, although the findings are suggestive of a potential difference in a more adequately powered study. Our results suggest that protamine sulfate is safe for intraoperative use without increased risk of thrombotic complications or early tibial bypass graft failure. [ABSTRACT FROM AUTHOR]

Complications from vascular access are the leading cause of morbidity in the hemodialysis population. The use of tunneled catheters is associated with a greater risk of bacteremia and mortality when compared to other types of hemodialysis access. Infective endocarditis is a serious complication occurring in 2–5% of patients undergoing hemodialysis and is likely secondary to transient bacteremia from repetitive vascular access. Objective: To review outcomes in hemodialysis-dependent patients requiring cardiac valve replacement for infective endocarditis. Methods: A retrospective chart review was conducted to identify all patients who underwent valve replacement within a six-year period (January 2009–December 2014). Inclusion criteria included a diagnosis of infective endocarditis and end stage renal disease on hemodialysis. Relevant clinical information including demographics, comorbidities, valve involvement, causative organisms, and type of hemodialysis access (arteriovenous fistula, arteriovenous graft, or tunneled catheter) was collected. Results: A total of 1497 patients underwent cardiac valve replacement within the six-year period. Of these, 167 patients (11.2%) had infective endocarditis and 119 patients (7.9%) had end stage renal disease on hemodialysis. Overall 30-day mortality for valve replacement was 5.0% (75/1497). Mortality for patients with infective endocarditis was 7.2% (12/167) and for patients with end stage renal disease on hemodialysis was 10.1% (12/119). Thirty-three patients (2.2%) had infective endocarditis and end stage renal disease on hemodialysis. Of these, 12 patients were being dialyzed via arteriovenous fistula, 4 via arteriovenous graft, and 17 via tunneled catheter. Mortality occurred in 2 of 12 patients with arteriovenous fistula, 1 of 4 patients with arteriovenous graft, and 2 of 17 patients with tunneled catheter for an overall mortality of 15.2% (5/33). Conclusion: Infective endocarditis remains a significant problem in patients with end stage renal disease on hemodialysis, particularly when tunneled catheters are utilized for hemodialysis access. Although appropriate algorithms have been developed to minimize long term use of tunneled catheters, bacteremia remains a significant problem. We reviewed our institutional experience and the medical literature to determine outcomes in hemodialysis-dependent patients with infective endocarditis requiring valve replacement. Despite mortality rates between 42 and 73% reported in the literature, our mortality rate was 15.2%. 1 Care of these critically ill patients must emphasize early diagnosis and aggressive management to optimize outcomes. [ABSTRACT FROM AUTHOR]

We present the performance characteristics of a digital output thin-film pyroelectric sensor for use in non-dispersive infra-red detection. The single channel pyroelectric sensor device was fitted with band-pass optical filter with a central wavelength of $4.26~\mu \text{m}$ for the detection of carbon dioxide. The classification reported here is concerned with the stability of the device for long-term measurements, with systematic drift not dominating measurement error even after 10 h operation. Comparative NDIR measurements were made for this novel pyroelectric device using two different optical sources, a standard filament lamp and a black body radiation source, operated at 5 Hz repetition rates. The overall limit of detection for the NDIR sensor was calculated to be 6 and 3 ppm for CO2 for the filament and blackbody source respectively, when the sensor was temperature stabilised at 35 °C and data was averaged over 110 min. The single shot measurement error was calculated to be 48 and 22 ppm for the lamp and blackbody, respectively, when the sensor temperature was stabilised at 35°C. The response of the detector to increasing temperature was found to exhibit a trend in the signal output directly proportional to the pyroelectric coefficient, this was also evident during flow tests when the flowing gas cooled the device. The result of changing both the concentration of analyte and flow rate is also covered. This is the first time the performance of a fully digital output pyroelectric detector has been reported. [ABSTRACT FROM AUTHOR]

Background We report a symptomatic carotid web successfully treated with carotid endarterectomy. A healthy 43-year-old woman presented with acute-onset left-sided weakness. Carotid web was evident on computed tomography angiography as a focal filling defect in the right common carotid artery. This right common carotid artery web extended into the ICA created an eddy resulting in turbulent flow. Subsequent acute embolus formation led to embolization and acute stroke. Method Review of the literature was performed using Medline Plus and PubMed databases. Result The patient underwent carotid endarterectomy with primary closure. Procedure was well tolerated and there was an uneventful recovery. Conclusion Arterial webs are a rare arteriopathy and a usual arrangement of fibromuscular intralumenal in-growth with unclear etiology. It is however, an important potential etiology of stroke in patients without traditional atherosclerotic risk factors. Carotid web and atypical carotid fibromuscular dysplasia should be considered in young, otherwise healthy patients presenting with stroke and without the typical risk factors for atherosclerotic carotid disease and stroke. [ABSTRACT FROM AUTHOR]

The Multicenter AIDS Cohort Study was designed to 1) elucidate the natural history of the infection causing acquired immunodeficiency syndrome (AIDS), 2) identify risk factors for occurrence and clinical expression of the infection, and 3) establish a repository of biologic specimens for future study. A variety of recruitment techniques, including special assurance of confidentiality, were used to enroll participants. Nearly 5,000 homosexual men volunteered for semiannual interview, physical examination, and laboratory testing in four metropolitan areas. A significant majority of these men in each center (69-83%) reported having 50 or more lifetime sexual partners, and over 80% had engaged in receptive anal intercourse with at least some of their partners in the previous two years. By the time of the participants' initial evaluation (April 1984-April 1985), infection with the human immunodeficiency virus (HIV) had occurred in higher proportions of men in Los Angeles (51%) and Chicago (43%) than in Baltimore/Washington, DC (31%) and Pittsburgh (21%), presumably as a result of the higher number of partners and proportion with whom these men had engaged in high-risk practices (e.g., receptive anal intercourse). Follow-up evaluations are underway in this comprehensive longitudinal investigation of HIV infection. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis is common among HIV-infected persons and contributes to risk of fragility fracture. While ART initiation is associated with decreases in bone mineral density and increases in bone turnover, the impact of HIV on bone metabolism is unclear.Methods: We identified men at the Chicago site of the Multicenter AIDS Cohort Study who HIV seroconverted while under observation. Concentrations of 25-OH vitamin D, bone turnover markers [procollagen type 1 N terminal propeptide (P1NP), osteocalcin (OC), C-telopeptide (CTX)] and sclerostin were measured from stored serum obtained at pre-HIV infection, pre-ART and post-ART initiation timepoints. Mixed models, with each biomarker as an outcome, were fitted. Timepoint, age, CD4 count (cells/mm 3 ), HIV-viral suppression, season and an age by timepoint interaction term were considered as fixed effects.Results: Data from 52 participants revealed that median duration between HIV seroconversion and ART initiation was 8.7 years (IQR 3.7-11.6). Median CD4 and plasma HIV-RNA concentrations were 445 (IQR 298.5-689) and 20 184 copies/mL (IQR 6237-64 340), respectively, at the pre-ART timepoint. Multivariate analyses demonstrated pre-HIV infection levels of OC that were higher than pre-ART levels (6.8 versus 5.7 ng/mL, P  =   0.04); and pre-ART levels of sclerostin that were higher than post-ART levels (0.033 versus 0.02 ng/mL, P  <0.001). No changes in P1NP, CTX and 25-OH vitamin D levels were detected.Conclusions: HIV seroconversion was associated with decreased OC levels while ART initiation was associated with decreases in sclerostin, a negative regulator of bone formation. Our results suggest that both HIV infection and ART have an impact on bone metabolism in white men. [ABSTRACT FROM AUTHOR]

Background: Men who have sex with men (MSM) are at high risk for hepatitis B virus (HBV) infection. Data on the effect of highly active antiretroviral therapy (HAART) on incident HBV infection in HIV-infected and HIV-uninfected MSM are limited.Objective: To determine predictors of incident HBV infection in MSM during pre-HAART and HAART periods.Design: Observational cohort study.Setting: Cohort of MSM who have, or are at risk for, HIV infection.Patients: 2375 HBV-uninfected MSM in the Multicenter AIDS Cohort Study.Measurements: Poisson regression was used to compare incidence rates of HBV infection in the pre-HAART and HAART eras and to identify factors associated with incidence of HBV infection.Results: In 25,322 person-years of follow-up, 244 incident HBV infections occurred. The unadjusted incidence rate was higher in HIV-infected MSM than in HIV-uninfected MSM (incidence rate ratio [IRR], 1.9 [95% CI, 1.5 to 2.4]) and was significantly lower in the HAART era than in the pre-HAART era among HIV-infected (IRR, 0.2 [CI, 0.1 to 0.4]) and HIV-uninfected (IRR, 0.3 [CI, 0.2 to 0.4]) MSM. Age younger than 40 years (IRR, 2.3 [CI, 1.7 to 3.0]), more than 1 recent sexual partner (IRR, 3.1 [CI, 2.3 to 4.2]), and HIV infection (IRR, 2.4 [CI, 1.8 to 3.1]) were independently associated with higher incidence of HBV infection, whereas HBV vaccination was protective (IRR, 0.3 [CI, 0.2 to 0.4]). Highly active antiretroviral therapy with HIV RNA levels less than 400 copies/mL was associated with protection (IRR, 0.2 [CI, 0.1 to 0.5]), but HAART in those with HIV RNA levels of 400 copies/mL or greater was not.Limitation: The observational nature limits inferences about causality.Conclusion: Effective HAART is associated with lower incidence of HBV infection; however, even in the HAART era, incidence of HBV infection remains high among MSM.Primary Funding Source: National Institute of Allergy and Infectious Diseases. [ABSTRACT FROM AUTHOR]

Background: The probability of spontaneous hepatitis C virus (HCV) clearance ranges from 11% to 49%. Our previous cross-sectional study suggests that mode of acquisition explains some of this heterogeneity. We performed this prospective study to determine factors associated with spontaneous HCV clearance among men who have sex with men (MSM). Methods: A mixture-cure model was used to evaluate the probability of spontaneous HCV clearance among 101 MSM in the Multicenter AIDS Cohort Study with acute HCV infection between 1984 and 2012. Results: Spontaneous HCV clearance occurred in 46% of MSM (49% in non-injection drug users [IDUs] and 23% in IDUs). In the multivariable analysis, age <30 years (clearance ratio [CR] = 2.43; 95% confidence interval [CI], 1.53-3.87) and being human immunodeficiency virus (HIV) uninfected (CR = 2.97; 95% CI, 1.98-4.46) were independently associated with spontaneous clearance. Among men aged =30 years, being HIV uninfected, not having unprotected anal intercourse, older age, and being on highly active antiretroviral therapy were independently associated with higher clearance. The interferon lambda rs12979860 single nucleotide polymorphism (SNP) was not associated with spontaneous clearance among the 88 MSM who were not active IDUs (CR = 0.74; 95% CI, .46-1.21 for CC vs CT/TT genotype). Conclusions: The high probability of spontaneous HCV clearance together with the lack of an association between the rs12979860 SNP and spontaneous clearance among MSM who do not use injection drugs suggests that the immune mechanisms involved with a successful response to acute HCV differ by mode of virus acquisition. Understanding potential mechanistic differences could be important for HCV vaccine development. [ABSTRACT FROM AUTHOR]

A 78-year-old gentleman presented with recurrent symptomatic hemarthrosis after total knee arthroplasty. His workup revealed an iatrogenic arteriovenous fistula (iAVF). The iAVF was embolized with the Onyx Liquid Embolization System with resolution of his symptoms up to 10 months of follow-up. This is the first description to our knowledge of an iatrogenic hemarthrosis after total knee arthroplasty successfully treated with Onyx solution embolization. [ABSTRACT FROM AUTHOR]

Background. Adults aging with HIV infection are at risk for age-related comorbidities and syndromes, such as frailty. The objective of this study was to evaluate the expression and predictors of the frailty phenotype (FP) among HIV-infected (HIV+) and HIV-uninfected (HIV−) men who have sex with men. Methods. A prospective, observational cohort study was nested in the Multicenter AIDS Cohort Study from October 2007–September 2011. FP conversion was defined as the onset of FP over two consecutive study visits. Adjusted odds ratios and 95% confidence intervals ([,]) for FP conversion were estimated using logistic regression models with generalized estimating equations. Results. Of 10,571 completed study visits from 1,946 men who have sex with men, 12% and 9% were FP+ among HIV+ and HIV− men, respectively (p = .002). The proportion of FP+ visits increased with age regardless of HIV status, but was significantly greater in HIV+ compared to HIV− men aged 50–64 years. Of the 10,276 consecutive visit pairs contributed by participants, 5% (537) were classified as FP conversion, and 45% of the men with FP conversion had only one FP+ study visit. FP conversion was significantly associated with a history of AIDS (adjusted odds ratios = 2.26 [1.50, 3.39], but not with HIV+ alone (adjusted odds ratios = 1.26 [0.98, 1.64]). Among men who had one or more FP+ visits, 34% of HIV+ and 38% of HIV− men had less than two comorbidities. Conclusions. These findings suggest that expression of the FP can be measured in men who have sex with men with and without HIV infection and reflects multisystem dysfunction in this population; further investigations are needed to better understand clinical utility. [ABSTRACT FROM PUBLISHER]

Objective: To review the incidence of respiratory conditions and their effect on mortality in HIV-infected and uninfected individuals prior to and during the era of highly active antiretroviral therapy (HAART). Design: Two large observational cohorts of HIV-infected and HIV-uninfected men (Multicenter AIDS Cohort Study [MACS]) and women (Women’s Interagency HIV Study [WIHS]), followed since 1984 and 1994, respectively. Methods: Adjusted odds or hazards ratios for incident respiratory infections or non-infectious respiratory diagnoses, respectively, in HIV-infected compared to HIV-uninfected individuals in both the pre-HAART (MACS only) and HAART eras; and adjusted Cox proportional hazard ratios for mortality in HIV-infected persons with lung disease during the HAART era. Results: Compared to HIV-uninfected participants, HIV-infected individuals had more incident respiratory infections both pre-HAART (MACS, odds ratio [adjusted-OR], 2.4; 95% confidence interval [CI], 2.2–2.7; p<0.001) and after HAART availability (MACS, adjusted-OR, 1.5; 95%CI 1.3–1.7; p<0.001; WIHS adjusted-OR, 2.2; 95%CI 1.8–2.7; p<0.001). Chronic obstructive pulmonary disease was more common in MACS HIV-infected vs. HIV-uninfected participants pre-HAART (hazard ratio [adjusted-HR] 2.9; 95%CI, 1.02–8.4; p = 0.046). After HAART availability, non-infectious lung diseases were not significantly more common in HIV-infected participants in either MACS or WIHS participants. HIV-infected participants in the HAART era with respiratory infections had an increased risk of death compared to those without infections (MACS adjusted-HR, 1.5; 95%CI, 1.3–1.7; p<0.001; WIHS adjusted-HR, 1.9; 95%CI, 1.5–2.4; p<0.001). Conclusion: HIV infection remained a significant risk for infectious respiratory diseases after the introduction of HAART, and infectious respiratory diseases were associated with an increased risk of mortality. [ABSTRACT FROM AUTHOR]

Parametric and semiparametric competing risks methods were used to estimate proportions, timing, and predictors of acquired immune deficiency syndrome (AIDS)-related and non-AIDS-related mortality among individuals both positive and negative for the human immunodeficiency syndrome (HIV) in the Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS) from 1984 to 2008 and 1996 to 2008, respectively. Among HIV-positive MACS participants, the proportion of deaths unrelated to AIDS increased from 6% before the introduction of highly active antiretroviral therapy (HAART) (before 1996) to 53% in the HAART era (P < 0.01); the median age of persons who died from non-AIDS-related causes after age 35 years increased from 49.0 to 66.0 years (P < 0.01). In both cohorts during the HAART era, median ages at time of non-AIDS-related death were younger for HIV-positive individuals than for comparable HIV-negative individuals (8.7 years younger in MACS (P < 0.01) and 7.6 years younger in WIHS (P < 0.01)). In a multivariate proportional cause-specific hazards model, unemployment (for non-AIDS death, hazard ratio (HR) = 1.8; for AIDS death, HR = 2.3), depression (for non-AIDS death, HR = 1.4; for AIDS death, HR = 1.4), and hepatitis B or C infection (for non-AIDS death, HR = 1.8, for AIDS death; HR = 1.4) were significantly (P < 0.05) associated with higher hazards of both non-AIDS and AIDS mortality among HIV-positive individuals in the HAART era, independent of study cohort. The results illuminate the changing face of mortality among the growing population infected with HIV. [ABSTRACT FROM AUTHOR]

Chromosome 3p21--22 harbors two clusters of chemokine receptor genes, several of which serve as major or minor coreceptors of HIV-1. Although the genetic association of CCR5 and CCR2 variants with HIV-1 pathogenesis is well known, the role of variation in other nearby chemokine receptor genes remain unresolved. We genotyped exonic single nucleotide polymorphisms (SNPs) in chemokine receptor genes: CCR3, CCRL2, and CXCR6 (at 3p21) and CCR8 and CX3CR1 (at 3p22), the majority of which were non-synonymous. The individual SNPs were tested for their effects on disease progression and outcomes in five treatment-nai ¨ve HIV-1/AIDS natural history cohorts. In addition to the known CCR5 and CCR2 associations, significant associations were identified for CCR3, CCR8, and CCRL2 on progression to AIDS. A multivariate survival analysis pointed to a previously undetected association of a non-conservative amino acid change F167Y in CCRL2 with AIDS progression: 167F is associated with accelerated progression to AIDS (RH = 1.90, P = 0.002, corrected). Further analysis indicated that CCRL2-167F was specifically associated with more rapid development of pneumocystis pneumonia (PCP) (RH = 2.84, 95% CI 1.28--6.31) among four major AIDS--defining conditions. Considering the newly defined role of CCRL2 in lung dendritic cell trafficking, this atypical chemokine receptor may affect PCP through immune regulation and inducing inflammation. [ABSTRACT FROM AUTHOR]

Background. In the general population, frailty, a late stage of the aging process, predicts mortality. We investigated whether manifesting a previously defined frailty-related phenotype (FRP) before initiating highly active antiretroviral therapy (HAART) affects the likelihood of developing clinical AIDS or mortality after HAART initiation. Methods. Among 596 HIV-infected men in the Multicenter AIDS Cohort Study whose date of HAART initiation was known within ±6 months and who had an assessable FRP status within 3 years before HAART, survival analyses were performed to assess the effect of FRP manifestation on clinical AIDS or death after HAART. Results. In men free of AIDS before HAART, AIDS or death after HAART occurred in 13/36 (36%) men who exhibited the FRP before HAART but only in 69/436 (16%) men who did not (hazard ratio = 2.6; 95% confidence interval = 1.4–4.6; p < .01). After adjusting for age, ethnicity, education, nadir CD4+ T-cell count, peak HIV viral load, and hemoglobin in the 3 years before HAART, having the FRP at >25% of visits in the 3 years before HAART significantly predicted AIDS or death (adjusted hazard ratio = 3.8; 95% confidence interval = 1.9–7.9; p < .01). Results were unchanged when the analysis was restricted to the 335 AIDS-free men who were HAART responders, to the 124 men who had AIDS at HAART initiation, or to the subsets of men for whom indices of liver and kidney function could be taken into account. Conclusion. Having a persistent frailty-like phenotype before HAART initiation predicted a worse prognosis after HAART, independent of known risk factors. [ABSTRACT FROM PUBLISHER]

HIV-1-infected adults over the age of 50 years progress to AIDS more rapidly than adults in their twenties or thirties. In addition, HIV-1-infected individuals receiving antiretroviral therapy (ART) present with clinical diseases, such as various cancers and liver disease, more commonly seen in older uninfected adults. These observations suggest that HIV-1 infection in older persons can have detrimental immunological effects that are not completely reversed by ART. As naïve T-cells are critically important in responses to neoantigens, we first analyzed two subsets (CD45RA+CD31+ and CD45RA+CD31-) within the naïve CD4+ T-cell compartment in young (20-32 years old) and older (39-58 years old), ART-naïve, HIV-1 seropositive individuals within 1-3 years of infection and in age-matched seronegative controls. HIV-1 infection in the young cohort was associated with lower absolute numbers of, and shorter telomere lengths within, both CD45RA+CD31+CD4+ and CD45RA+CD31-CD4+ T-cell subsets in comparison to age-matched seronegative controls, changes that resembled seronegative individuals who were decades older. Longitudinal analysis provided evidence of thymic emigration and reconstitution of CD45RA+CD31+CD4+ T-cells two years post-ART, but minimal reconstitution of the CD45RA+CD31-CD4+ subset, which could impair de novo immune responses. For both ART-naïve and ART-treated HIV-1-infected adults, a renewable pool of thymic emigrants is necessary to maintain CD4+ T-cell homeostasis. Overall, these results offer a partial explanation both for the faster disease progression of older adults and the observation that viral responders to ART present with clinical diseases associated with older adults. [ABSTRACT FROM AUTHOR]

Background. The compilation of previous genomewide association studies of AIDS shows a major polymorphism in the HCP5 gene associated with both control of the viral load and long-term nonprogression (LTNP) to AIDS. Methods. To look for genetic variants that affect LTNP without necessary control of the viral load, we reanalyzed the genomewide data of the unique LTNP Genomics of Resistance to Immunodeficiency Virus (GRIV) cohort by excluding "elite controller" patients, who were controlling the viral load at very low levels (<100 copies/mL). Results. The rs2234358 polymorphism in the CXCR6 gene was the strongest signal (P = 2.5 × 10-7; odds ratio, 1.85) obtained for the genomewide association study comparing the 186 GRIV LTNPs who were not elite controllers with 697 uninfected control subjects. This association was replicated in 3 additional independent European studies, reaching genomewide significance of Pcombined = 9.7 × 10-10. This association with LTNP is independent of the CCR2-CCR5 locus and the HCP5 polymorphisms. Conclusions. The statistical significance, the replication, and the magnitude of the association demonstrate that CXCR6 is likely involved in the molecular etiology of AIDS and, in particular, in LTNP, emphasizing the power of extreme-phenotype cohorts. CXCR6 is a chemokine receptor that is known as a minor coreceptor in human immunodeficiency virus type 1 infection but could participate in disease progression through its role as a mediator of inflammation. [ABSTRACT FROM AUTHOR]

We attempted to refine the understanding of an association of Y-chromosomal haplogroup I (hg-I) with enhanced AIDS progression that had been previously reported. First, we compared the progression phenotype between hg-I and its phylogenetically closest haplogroup J. Then, we took a candidate gene approach resequencing DDX3Y, a crucial autoimmunity gene, in hg-I and other common European Y-chromosome haplogroups looking for functional variants. We extended the genetic analyses to CD24L4 and compared and contrasted the roles of disease-based selection, demographic history and population structure shaping the contemporary genetic landscape of hg-I chromosomes. Our results confirmed and refined the AIDS progression signal to hg-I, though no gene variant was identified that can explain the disease association. Molecular evolutionary and genetic analyses of the examined loci suggested a unique evolutionary history in hg-I, probably shaped by complex interactions of selection, demographic history and high geographical differentiation leading to the formation of distinct hg-I subhaplogroups that today are associated with HIV/AIDS onset. Clearly, further studies on Y-chromosome candidate loci sequencing to discover functional variants and discern the roles of evolutionary factors are warranted. [ABSTRACT FROM AUTHOR]

The human APOBEC3 family of cytidine deaminases provides intrinsic immunity to retroviral infection. A naturally occurring 29.5-kb deletion removes the entire APOBEC3B gene. We examined the impact of the APOBEC3B gene deletion in 14000 individuals from 5 human immunodeficiency virus type 1 (HIV-1) natural history cohorts. The hemizygous genotype had no effect on either acquisition of HIV-1 infection or progression to AIDS. However, the homozygous deletion was significantly associated with unfavorable outcomes for HIV-1 acquisition (odds ratio, 7.37; P = .024), progres- sion to AIDS (relative hazard, 4.01; P = .03), and viral set point (P = .04). These findings suggest that the loss of APO- BEC3B may increase host susceptibility to HIV-1 acquisition and progression to AIDS and warrant further study. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding a study on the role of CCL3L1 gene copy number on the risk for HIV infection and AIDS as well as in disease progression.

Background: As availability of primary cells can be limited for genetic studies of human disease, lymphoblastoid cell lines (LCL) are common sources of genomic DNA. LCL are created in a transformation process that entails in vitro infection of human B-lymphocytes with the Epstein-Barr Virus (EBV). Methodology/Principal Findings: To test for genotypic errors potentially induced by the Epstein-Barr Virus transformation process, we compared single nucleotide polymorphism (SNP) genotype calls in peripheral blood mononuclear cells (PBMC) and LCL from the same individuals. The average mismatch rate across 19 comparisons was 0.12% for SNPs with a population call rate of at least 95%, and 0.03% at SNPs with a call rate of at least 99%. Mismatch rates were not correlated across genotype subarrays run on all sample pairs. Conclusions/Significance: Genotypic discrepancies found in PBMC and LCL pairs were not significantly different than control pairs, and were not correlated across subarrays. These results suggest that mismatch rates are minimal with stringent quality control, and that most genotypic discrepancies are due to technical artifacts rather than the EBV transformation process. Thus, LCL likely constitute a reliable DNA source for host genotype analysis. [ABSTRACT FROM AUTHOR]

The host genetic basis of differential outcomes in HIV infection, progression, viral load set point and highly active retroviral therapy (HAART) responses was examined for the common Y haplogroups in European Americans and African Americans. Accelerated progression to acquired immune deficiency syndrome (AIDS) and related death in European Americans among Y chromosome haplogroup I (Y-I) subjects was discovered. Additionally, Y-I haplogroup subjects on HAART took a longer time to HIV-1 viral suppression and were more likely to fail HAART. Both the accelerated progression and longer time to viral suppression results observed in haplogroup Y-I were significant after false-discovery-rate corrections. A higher frequency of AIDS-defining illnesses was also observed in haplogroup Y-I. These effects were independent of the previously identified autosomal AIDS restriction genes. When the Y-I haplogroup subjects were further subdivided into six I subhaplogroups, no one subhaplogroup accounted for the effects on HIV progression, viral load or HAART response. Adjustment of the analyses for population stratification found significant and concordant haplogroup Y-I results. The Y chromosome haplogroup analyses of HIV infection and progression in African Americans were not significant. Our results suggest that one or more loci on the Y chromosome found on haplogroup Y-I have an effect on AIDS progression and treatment responses in European Americans. [ABSTRACT FROM AUTHOR]

We examined the emergence of CXCR4 (i.e., X4) tropism in 67 male human immunodeficiency virus type 1 (HIV-1) seroconverters from the Multicenter AIDS Cohort Study (MACS) who were selected to reflect the full spectrum of rates of HIV-1 disease progression. A mean of 10 serial samples per donor were evaluated by a laboratory-validated, commercially available assay to determine phenotypic coreceptor use.Atotal of52%ofmen had dual- or mixed-tropic HIV-1 detected at 1 or more of the time points tested. Use of X4 by HIV-1 was detected more frequently among men who developed AIDS (defined as a CD4+ T cell count of <200 cells/μL and/or an AIDS-defining illness)⩽11 years after seroconversion thanamongthosewhodid not (P = .005), as well asamong men who exhibited a total T cell count decline (i.e., a CD3+ inflection point), compared with those who did not (P = .03). Formen in whom both X4 virus and an inflection point were detected, emergence of X4 virus preceded the inflection point by a median of 0.83 years. The median CD4+ T cell count at first detection of X4 viruses before the onset of AIDS was 475 cells/μL. We conclude that HIV-1 variants that used X4 frequently emerged at high CD4+ T cell counts and may contribute to the decrease in T cell numbers during late HIV-1 infection. [ABSTRACT FROM AUTHOR]

Concentrated zirconia pastes require optimization before they can be used in large-scale screen-printing processes in solid oxide fuel cells (SOFC) manufacture. The present article investigates a series of terpineol-based zirconia pastes stabilized with ethyl cellulose of varying concentrations by combined rheological methods. Small additions of ethyl cellulose (up to 0.50 vol%) resulted in a significant increase in the shear viscosity, shear stress, and network strength of the pastes. In comparison with the properties of the ink vehicles, the observed elastic response of the ink pastes on the initiation of flow was attributed to the interaction of ethyl cellulose with the zirconia particles. This interaction was confirmed to be bridging flocculation by rheological methods. Start-up shear flow experiments assessed the elastic deformation of the pastes in greater detail. Application of transient network theory (TNT) to describe the properties of the pastes was confirmed by the linear dependence of the equilibrium shear modulus ( G∞) with increasing ethyl cellulose concentration. TNT provides a basis for explaining the rheological effects of bridging polymers in network suspensions and assessing their interaction with other organic additives in high solids volume suspensions. This is a useful analysis for optimizing suspensions for screen-printing SOFC components among other applications. [ABSTRACT FROM AUTHOR]

Background: Detection of HIV-1 in patients is limited by the sensitivity and selectivity of available tests. The nanotechnology-based bio-barcode-amplification method offers an innovative approach to detect specific HIV-1 antigens from diverse HIV-1 subtypes. We evaluated the efficacy of this protein-detection method in detecting HIV-1 in men enrolled in the Chicago component of the Multicenter AIDS Cohort Study (MACS). Methods: The method relies on magnetic microparticles with antibodies that specifically bind the HIV-1 p24 Gag protein and nanoparticles that are encoded with DNA and antibodies that can sandwich the target protein captured by the microparticle-bound antibodies. The aggregate sandwich structures are magnetically separated from solution, and treated to remove the conjugated barcode DNA. The DNA barcodes (hundreds per target) were identified by a nanoparticle-based detection method that does not rely on PCR. Results: Of 112 plasma samples from HIV-1-infected subjects, 111 were positive for HIV-1 p24 Gag protein (range: 0.11-71.5 ng/ml of plasma) by the bio-barcode-amplification method. HIV-1 p24 Gag protein was detected in only 23 out of 112 men by the conventional ELISA. A total of 34 uninfected subjects were negative by both tests. Thus, the specificity of the bio-barcode-amplification method was 100% and the sensitivity 99%. The bio-barcode-amplification method detected HIV-1 p24 Gag protein in plasma from all study subjects with less than 200 CD4+ T cells/µl of plasma (100%) and 19 out of 20 (95%) HIV-1-infected men who had less than 50 copies/ml of plasma of HIV-1 RNA. In a separate group of 60 diverse international isolates, representative of clades A, B, C and D and circulating recombinant forms CRF01_AE and CRF02_AG, the bio-barcode-amplification method identified the presence of virus correctly. Conclusions: The bio-barcode-amplification method was superior to the conventional ELISA assay for the detection of HIV-1 p24 Gag protein in plasma with a breadth of coverage for diverse HIV-1 subtypes. Because the bio-barcode-amplification method does not require enzymatic amplification, this method could be translated into a robust point-of-care test. [ABSTRACT FROM AUTHOR]

Background. Several long-term cohort studies and in-vitro fitness assays have resulted in inconsistent reports on changes in HIV-1 virulence, including reports of decreasing, stable, and increasing virulence over the course of the AIDS pandemic. We tested the hypothesis of changing HIV-1 virulence by examining trends in prognostic clinical markers of disease progression from 1984 to 2005 among nearly 400 antiretroviral-naïve participants in the United States Multicenter AIDS Cohort Study (MACS), a longitudinal study of HIV infection in men who have sex with men (MSM). Methodology/Principal Findings. Because clinical AIDS endpoints could not be used (due to antiretroviral therapies and prophylaxis), three prognostic markers of disease progression were used as proxies for HIV-1 virulence: plasma viral RNA load and CD4+ T cell count at "set point" (between ∼9 and ∼15 months after seroconversion), and rate of CD4 cell decline within three years after seroconversion. We performed multivariate analyses of the association between these markers and seroconversion year, with covariates including MACS site, race/ethnic group, seroconversion age, and CCR5Δ32 status. No statistically significant association was found between year of seroconversion and "set point" plasma viral load (at ∼9 months after seroconversion: slope =-0.004 log10 copies/mL/year, p = 0.76; at ∼15 months: slope =-0.005 log10 copies/mL/year, p = 0.71), CD4 cell count after seroconversion (at ∼9 months: slope =-0.112 cells/μL/year, p = 0.22; at ∼15 months: slope =-0.047 cells/μL/year, p = 0.64), or rate of CD4 cell decline over the first three years after seroconversion (slope =-0.010 cells/ul/yr2, p = 0.88). Conclusions/Significance. The lack of significant trends from 1984 to 2005 in these prognostic markers of HIV disease progression suggests no major change in HIV-1 virulence over the AIDS pandemic in MSM in the US. [ABSTRACT FROM AUTHOR]