Ian Metzler

Public clonotype usage identifies protective Gag-specific CD8+ T cell responses in SIV infection

Despite the pressing need for an AIDS vaccine, the determinants of protective immunity to HIV remain concealed within the complexity of adaptive immune responses. We dissected immunodominant virus-specific CD8+ T cell populations in Mamu-A*01+ rhesus macaques with primary SIV infection to elucidate the hallmarks of effective immunity at the level of individual constituent clonotypes, which were identified according to the expression of distinct T cell receptors (TCRs). The number of public clonotypes, defined as those that expressed identical TCR β-chain amino acid sequences and recurred in multiple individuals, contained within the acute phase CD8+ T cell population specific for the biologically constrained Gag CM9 (CTPYDINQM; residues 181–189) epitope correlated negatively with the virus load set point. This independent molecular signature of protection was confirmed in a prospective vaccine trial, in which clonotype engagement was governed by the nature of the antigen rather than the context of exposure and public clonotype usage was associated with enhanced recognition of epitope variants. Thus, the pattern of antigen-specific clonotype recruitment within a protective CD8+ T cell population is a prognostic indicator of vaccine efficacy and biological outcome in an AIDS virus infection.

Obstructed Labor and Caesarean Delivery: The Cost and Benefit of Surgical Intervention

Background Although advances in the reduction of maternal mortality have been made, up to 273,000 women will die this year from obstetric etiologies. Obstructed labor (OL), most commonly treated with Caesarean delivery, has been identified as a major contributor to global maternal morbidity and mortality. We used economic and epidemiological modeling to estimate the cost per disability-adjusted life-year (DALY) averted and benefit-cost ratio of treating OL with Caesarean delivery for 49 countries identified as providing an insufficient number of Caesarean deliveries to meet demand. Methods and Findings Using publicly available data and explicit economic assumptions, we estimated that the cost per DALY (3,0,0) averted for providing Caesarean delivery for OL ranged widely, from

Minor viral and host genetic polymorphisms can dramatically impact the biologic outcome of an epitope-specific CD8 T-cell response

251 per DALY averted in Madagascar to

Emergency Department Imaging Modality Effect on Surgical Management of Nephrolithiasis: A Multicenter, Randomized Clinical Trial.

3,462 in Oman. The median cost per DALY averted was

Cycling, and Male Sexual and Urinary Function: Results from a Large, Multinational, Cross-Sectional Study

304. Benefit-cost ratios also varied, from 0.6 in Zimbabwe to 69.9 in Gabon. The median benefit-cost ratio calculated was 6.0. The main limitation of this study is an assumption that lack of surgical capacity is the main factor responsible for DALYs from OL. Conclusions Using the World Health Organizations cost-effectiveness standards, investing in Caesarean delivery can be considered “highly cost-effective” for 48 of the 49 countries included in this study. Furthermore, in 46 of the 49 included countries, the benefit-cost ratio was greater than 1.0, implying that investment in Caesarean delivery is a viable economic proposition. While Caesarean delivery alone is not sufficient for combating OL, it is necessary, cost-effective by WHO standards, and ultimately economically favorable in the vast majority of countries included in this study.

Micro-costing analysis demonstrates comparable costs for LithoVue™ compared to reusable flexible fiberoptic ureteroscopes

Human immunodeficiency virus-1 subtypes A and C differ in the highly conserved Gag-TL9 epitope at a single amino acid position. Similarly, the TL9 presenting human leukocyte antigen (HLA) class I molecules B42 and B81 differ only at 6 amino acid positions. Here, we addressed the influence of such minor viral and host genetic variation on the TL9-specific CD8 T-cell response. The clonotypic characteristics of CD8 T-cell populations elicited by subtype A or subtype C were distinct, and these responses differed substantially with respect to the recognition and selection of TL9 variants. Irrespective of the presenting HLA class I molecule, CD8 T-cell responses elicited by subtype C exhibited largely comparable TL9 variant cross-recognition properties, expressed T-cell receptors that used almost exclusively the TRBV 12-3 gene, and selected for predictable patterns of viral variation within TL9. In contrast, subtype A elicited TL9-specific CD8 T-cell populations with completely different, more diverse TCRBV genes and did not select for viral variants. Moreover, TL9 variant cross-recognition properties were extensive in B81(+) subjects but limited in B42(+) subjects. Thus, minor viral and host genetic polymorphisms can dramatically alter the immunologic and virologic outcome of an epitope-specific CD8 T-cell response.

Ultrasound Guidance Reduces Percutaneous Nephrolithotomy Cost Compared to Fluoroscopy

Purpose: In the emergency department ultrasonography is emerging as an alternative to computerized tomography for diagnosing patients with nephrolithiasis. In this multicenter randomized clinical trial we examined rates of urological referral and intervention to elucidate whether the initial diagnostic imaging modality affected the management of nephrolithiasis. Materials and Methods: Patients 18 to 76 years old who presented to the emergency department with renal colic across 15 diverse treatment centers were randomized to receive abdominal ultrasonography by an emergency department physician or a radiologist, or abdominal computerized tomography. We analyzed the 90‐day followup for patients diagnosed with nephrolithiasis to assess subsequent urological evaluation, procedure type and time to intervention. Results: Of 1,666 patients diagnosed with nephrolithiasis in the emergency department 241 (14.5%) had a consultation with urology at initial presentation, 503 (30%) saw a urologist in followup and 192 (12%) underwent at least 1 urological procedure. Median time to outpatient procedure and type of procedure performed did not vary significantly among imaging groups. Most patients (78%) had computerized tomography performed before elective intervention. Patients with ultrasonography performed by an emergency department physician were 2.6 times more likely to undergo computerized tomography before intervention than those who had ultrasonography performed by a radiologist. Conclusions: Patients undergoing a urological intervention who had ultrasonography as initial imaging do not experience a significant delay to intervention or different procedure types, but the majority ultimately undergoes computerized tomography before surgery. Formal ultrasonography by a radiologist may encourage less computerized tomography preoperatively.

Suspected penile fracture: to operate or not to operate?

Purpose We explored the relation of cycling to urinary and sexual function in a large multinational sample of men. Materials and Methods Cyclists were recruited to complete a survey through Facebook® advertisements and outreach to sporting clubs. Swimmers and runners were recruited as a comparison group. Cyclists were categorized into low and high intensity cyclists. Participants were queried using validated questionnaires, including SHIM (Sexual Health Inventory for Men), I‐PSS (International Prostate Symptom Score) and NIH‐CPSI (National Institutes of Health Chronic Prostatitis Symptom Index), in addition to questions about urinary tract infections, urethral stricture, genital numbness and saddle sores. Results Of 5,488 complete survey responses 3,932 (72%) were included in our analysis. On multivariate analysis swimmers/runners had a lower mean SHIM score than low and high intensity cyclists (19.5 vs 19.9 and 20.7, p = 0.02 and <0.001, respectively). No significant differences were found in I‐PSS or NIH‐CPSI scores, or urinary tract infection history. Cyclists had statistically higher odds of urethral stricture compared to swimmers/runners (OR 2.5, p = 0.042). Standing more than 20% of the time while cycling significantly reduced the odds of genital numbness (OR 0.4, p = 0.006). Adjusting the handlebar higher or even with the saddle had lower odds of genital numbness and saddle sores (OR 0.8, p = 0.005 and 0.6, p <0.001, respectively). Conclusions Cyclists had no worse sexual or urinary functions than swimmers or runners but cyclists were more prone to urethral stricture. Increased time standing while cycling and a higher handlebar height were associated with lower odds of genital sores and numbness.

Ultrasound-Guided Morcellation During Holmium Laser Enucleation of the Prostate

INTRODUCTION Reusable ureteroscope durability and need for repair are significant sources of expense and inefficiency for patients and urologists. Utilization of LithoVue™, a disposable flexible digital ureteroscope, may address some of these concerns. To identify its economic impact on clinical care, we performed a micro-cost comparison between flexible reusable fiberoptic ureteroscopes (URF-P6™) and LithoVue. PATIENTS AND METHODS For this prospective, single-center micro-costing study, all consecutive ureteroscopies performed during 1 week each in July and August 2016 utilized either URF-P6 or LithoVue ureteroscopes respectively. Workflow data were collected, including intraoperative events, postoperative reprocessing cycle timing, consumables usage, and ureteroscope cost data. RESULTS Intraoperative data analysis showed mean total operating room time for URF-P6 and LithoVue cases were 93.4 ± 32.3 and 73.6 ± 17.4 minutes, respectively (p = 0.093). Mean cost of operating room usage per case was calculated at

MP32-15 CARE PATHWAY VARIATION AND SURGICAL COST MEASUREMENT FOR PERCUTANEOUS NEPHROLITHOTOMY WITH TIME-DRIVEN ACTIVITY-BASED COSTING

1618.72 ± 441.39 for URF-P6 and