Transmission Bottleneck Size Estimation from De Novo Viral Genetic Variation.

Sequencing of viral infections has become increasingly common over the last decade. Deep sequencing data in particular have proven useful in characterizing the roles that genetic drift and natural selection play in shaping within-host viral populations. They have also been used to estimate transmission bottleneck sizes from identified donor-recipient pairs. These bottleneck sizes quantify the number of viral particles that establish genetic lineages in the recipient host and are important to estimate due to their impact on viral evolution. Current approaches for estimating bottleneck sizes exclusively consider the subset of viral sites that are observed as polymorphic in the donor individual. However, these approaches have the potential to substantially underestimate true transmission bottleneck sizes. Here, we present a new statistical approach for instead estimating bottleneck sizes using patterns of viral genetic variation that arise de novo within a recipient individual. Specifically, our approach makes use of the number of clonal viral variants observed in a transmission pair, defined as the number of viral sites that are monomorphic in both the donor and the recipient but carry different alleles. We first test our approach on a simulated dataset and then apply it to both influenza A virus sequence data and SARS-CoV-2 sequence data from identified transmission pairs. Our results confirm the existence of extremely tight transmission bottlenecks for these 2 respiratory viruses.

Imaging micrometer-sized aerosol particles with digital holography.

Small particles that are trapped, deposited, or otherwise fixed can be imaged by digital holography with a resolution approaching that of optical microscopy. When such particles are in motion as an aerosol, a comparable resolution is challenging to achieve. Using a simplified bi-telecentric lens system, we demonstrate that 1µm free-flowing aerosol particles can be imaged at the single-particle level using digital in-line holography. The imaging is demonstrated with an aerosol of 1µm polystyrene latex microspheres and a ragweed pollen aerosol.

A Pilot Study of Pembrolizumab Combined With Stereotactic Ablative Radiotherapy for Patients With Advanced or Metastatic Sarcoma.

OBJECTIVES: Immunotherapy with immune checkpoint inhibitors has shown only limited success in the management of metastatic soft tissue sarcoma. Overall response rates (ORR) with single agent pembrolizumab were 18% and median PFS was 18 weeks on the clinical trial SARC028. One strategy to improve the responses to immunotherapy is with stereotactic body radiation therapy (SBRT), which can enhance the antitumor CD8 T cell response through the release of tumor-specific antigens, potentially priming a more diverse class of T cell receptors. METHODS: This is a phase 0, pilot prospective study taking place at a single center with 2 arms. In Arm A, patients are treated with pembrolizumab 400 mg IV infusion on day 1 of a 42-day cycle. Stereotactic body radiation therapy (SBRT) is delivered in 1-5 fractions starting on C1D15-28 and given every other day. In Arm B, patients who have started an immune checkpoint inhibitor within 60 days are treated with SBRT in addition to the current therapy. RESULTS: In this study we outline testing the feasibility of adding SBRT to pembrolizumab. CONCLUSION: The ultimate goal of combination therapy is improved overall response, including tumors not treated with SBRT. This trial can be found registered online: NCT05488366.

Cellular co-infection can modulate the efficiency of influenza A virus production and shape the interferon response.

During viral infection, the numbers of virions infecting individual cells can vary significantly over time and space. The functional consequences of this variation in cellular multiplicity of infection (MOI) remain poorly understood. Here, we rigorously quantify the phenotypic consequences of cellular MOI during influenza A virus (IAV) infection over a single round of replication in terms of cell death rates, viral output kinetics, interferon and antiviral effector gene transcription, and superinfection potential. By statistically fitting mathematical models to our data, we precisely define specific functional forms that quantitatively describe the modulation of these phenotypes by MOI at the single cell level. To determine the generality of these functional forms, we compare two distinct cell lines (MDCK cells and A549 cells), both infected with the H1N1 strain A/Puerto Rico/8/1934 (PR8). We find that a model assuming that infected cell death rates are independent of cellular MOI best fits the experimental data in both cell lines. We further observe that a model in which the rate and efficiency of virus production increase with cellular co-infection best fits our observations in MDCK cells, but not in A549 cells. In A549 cells, we also find that induction of type III interferon, but not type I interferon, is highly dependent on cellular MOI, especially at early timepoints. This finding identifies a role for cellular co-infection in shaping the innate immune response to IAV infection. Finally, we show that higher cellular MOI is associated with more potent superinfection exclusion, thus limiting the total number of virions capable of infecting a cell. Overall, this study suggests that the extent of cellular co-infection by influenza viruses may be a critical determinant of both viral production kinetics and cellular infection outcomes in a host cell type-dependent manner.

Longitudinal Analysis of Mental Disorder Burden Among Elderly Patients With Gastrointestinal Malignancies.

BACKGROUND: Patients with cancer are at high risk for having mental disorders, resulting in widespread psychosocial screening efforts. However, there is a need for population-based and longitudinal studies of mental disorders among patients who have gastrointestinal cancer and particular among elderly patients. PATIENTS AND METHODS: We used the SEER-Medicare database to identify patients aged ≥65 years with colorectal, pancreatic, gastric, hepatic/biliary, esophageal, or anal cancer. Earlier (12 months before or up to 6 months after cancer diagnosis) and subsequent mental disorder diagnoses were identified. RESULTS: Of 112,283 patients, prevalence of an earlier mental disorder was 21%, 23%, 20%, 20%, 19%, and 26% for colorectal, pancreatic, gastric, hepatic/biliary, esophageal, and anal cancer, respectively. An increased odds of an earlier mental disorder was associated with pancreatic cancer (odds ratio [OR], 1.17; 95% CI, 1.11-1.23), esophageal cancer (OR, 1.10; 95% CI, 1.02-1.18), and anal cancer (OR, 1.17; 95% CI, 1.05-1.30) compared with colorectal cancer and with having regional versus local disease (OR, 1.09; 95% CI, 1.06-1.13). The cumulative incidence of a subsequent mental disorder at 5 years was 19%, 16%, 14%, 13%, 12%, and 10% for patients with anal, colorectal, esophageal, gastric, hepatic/biliary, and pancreatic cancer, respectively. There was an association with having regional disease (hazard ratio [HR], 1.08; 95% CI, 1.04-1.12) or distant disease (HR, 1.36; 95% CI, 1.28-1.45) compared with local disease and the development of a mental disorder. Although the development of a subsequent mental disorder was more common among patients with advanced cancers, there continued to be a significant number of patients with earlier-stage disease at risk. CONCLUSIONS: This study suggests a larger role for incorporating psychiatric symptom screening and management throughout oncologic care.

VarSight: prioritizing clinically reported variants with binary classification algorithms.

BACKGROUND: When applying genomic medicine to a rare disease patient, the primary goal is to identify one or more genomic variants that may explain the patient's phenotypes. Typically, this is done through annotation, filtering, and then prioritization of variants for manual curation. However, prioritization of variants in rare disease patients remains a challenging task due to the high degree of variability in phenotype presentation and molecular source of disease. Thus, methods that can identify and/or prioritize variants to be clinically reported in the presence of such variability are of critical importance. METHODS: We tested the application of classification algorithms that ingest variant annotations along with phenotype information for predicting whether a variant will ultimately be clinically reported and returned to a patient. To test the classifiers, we performed a retrospective study on variants that were clinically reported to 237 patients in the Undiagnosed Diseases Network. RESULTS: We treated the classifiers as variant prioritization systems and compared them to four variant prioritization algorithms and two single-measure controls. We showed that the trained classifiers outperformed all other tested methods with the best classifiers ranking 72% of all reported variants and 94% of reported pathogenic variants in the top 20. CONCLUSIONS: We demonstrated how freely available binary classification algorithms can be used to prioritize variants even in the presence of real-world variability. Furthermore, these classifiers outperformed all other tested methods, suggesting that they may be well suited for working with real rare disease patient datasets.

Prognostic Significance of P16 Expression and P53 Expression in Primary Vaginal Cancer.

To evaluate the correlation between p16 expression and clinical outcomes in patients with primary vaginal cancer treated with definitive radiotherapy. P16 immunohistochemical was performed on 25 patient samples and recorded from pathology reports in 7 patients. P53 immunohistochemical was performed on 3 p16-negative samples. Baseline characteristics were compared using the Fisher exact test. Outcomes were compared using log-rank tests, and cox proportional hazards models. Survival and recurrence analysis was performed with the Kaplan-Meier method and cumulative incidence estimates. P16 expression was positive in 29 patients and negative in 3 patients. Two of the p16-negative tumors showed positive expression of p53. The median overall survival, progression-free survival and 2-yr cumulative incidence of recurrence were 66 mo [95% confidence interval (CI), 31-96], 34 mo (95% CI, 21-86), and 19% (95% CI, 7%-34%), respectively. P16-positive tumors had higher median overall survival and progression-free survival compared with p16-negative tumors (82 vs. 31 mo, P=0.02 and 35 vs 16 mo, P=0.04, respectively). The 2-yr cumulative incidence of recurrence was 14% for p16-positive tumors compared with 67% for p16-negative tumors (P=0.07). On univariable analysis, p16-negative status, age older than 65, and advanced stage were associated with inferior overall survival. P16 negativity is an independent predictor of inferior overall survival. P16-positive vaginal cancers have a better prognosis and decreased incidence of recurrence compared with p16-negative tumors. These prognostic findings associated with p16-negative vaginal cancers will need to be confirmed in larger patient cohorts.

Accounting for cellular-level variation in lysis: implications for virus-host dynamics.

Viral impacts on microbial populations depend on interaction phenotypes-including viral traits spanning the adsorption rate, latent period, and burst size. The latent period is a key viral trait in lytic infections. Defined as the time from viral adsorption to viral progeny release, the latent period of bacteriophage is conventionally inferred via one-step growth curves in which the accumulation of free virus is measured over time in a population of infected cells. Developed more than 80 years ago, one-step growth curves do not account for cellular-level variability in the timing of lysis, potentially biasing inference of viral traits. Here, we use nonlinear dynamical models to understand how individual-level variation of the latent period impacts virus-host dynamics. Our modeling approach shows that inference of the latent period via one-step growth curves is systematically biased-generating estimates of shorter latent periods than the underlying population-level mean. The bias arises because variability in lysis timing at the cellular level leads to a fraction of early burst events, which are interpreted, artefactually, as an earlier mean time of viral release. We develop a computational framework to estimate latent period variability from joint measurements of host and free virus populations. Our computational framework recovers both the mean and variance of the latent period within simulated infections including realistic measurement noise. This work suggests that reframing the latent period as a distribution to account for variability in the population will improve the study of viral traits and their role in shaping microbial populations.IMPORTANCEQuantifying viral traits-including the adsorption rate, burst size, and latent period-is critical to characterize viral infection dynamics and develop predictive models of viral impacts across scales from cells to ecosystems. Here, we revisit the gold standard of viral trait estimation-the one-step growth curve-to assess the extent to which assumptions at the core of viral infection dynamics lead to ongoing and systematic biases in inferences of viral traits. We show that latent period estimates obtained via one-step growth curves systematically underestimate the mean latent period and, in turn, overestimate the rate of viral killing at population scales. By explicitly incorporating trait variability into a dynamical inference framework that leverages both virus and host time series, we provide a practical route to improve estimates of the mean and variance of viral traits across diverse virus-microbe systems.

Refining Target Volume Coverage After Parotidectomy for Cutaneous Squamous Cell Carcinoma: Omission of the Cervical Neck From the Radiation Field.

Purpose: For patients without pathologic evidence of cervical disease after neck dissection for cutaneous squamous cell carcinoma involving the parotid region, inclusion of the ipsilateral cervical neck in the postparotidectomy radiation volume is routinely performed. We report our experience with selective avoidance of the ipsilateral neck for patients undergoing postoperative radiation to the parotid bed. Methods and Materials: From January 2014 to December 2023, a total of 30 consecutive patients underwent postoperative radiation after parotidectomy for cutaneous squamous cell carcinoma involving the parotid area. All patients had previously had a neck dissection confirming pathologic N0 disease. Treatment was delivered using intensity modulated radiation therapy to a median dose of 60 Gy (range, 56-66 Gy). The radiation target volumes included the parotid bed only, with deliberate avoidance of the ipsilateral cervical neck. The median pathologic tumor size of the parotid tumor was 3.3 cm (range, 0.2-9.4 cm). Final pathologic evaluation showed positive microscopic margins in 8 patients (27%), perineural invasion in 17 patients (57%), and facial nerve involvement in 6 patients (20%). Results: There were no isolated nodal failures. One patient developed an ipsilateral neck recurrence approximately 8 months after completion of radiation therapy. This occurred 2 months subsequent to the development of local recurrence. The 5-year actuarial rates of local (parotid) control, neck control, and overall survival were 87%, 97%, and 76%, respectively. Conclusions: Omission of the ipsilateral neck from the parotid volume does not compromise disease control for pathologically N0 patients undergoing postoperative radiation for cutaneous squamous cell carcinoma involving the parotid region. Practical implications are discussed.

Re-irradiation versus systemic therapy for the management of local-regionally recurrent head and neck cancer.

PURPOSE: The optimal management of local-regionally recurrent head and neck cancer that is not amenable to surgical resection is uncertain. We sought to compare outcomes among patients treated with and without re-irradiation in this setting. METHODS AND MATERIALS: A review of institutional registries identified 65 patients with local-regionally recurrent squamous cell carcinoma of the head and neck who were ineligible for surgery. Forty patients (62 %) opted for re-irradiation with the remaining 25 patients (38 %) undergoing initial systemic therapy alone. All patients had measurable disease. Forty-three patients (66 %) were male and twenty-two (33 %) were female. The median age at the time of recurrence was 59 years (range, 39-84 years). The most common primary sites of disease were the oropharynx, (n = 25), oral cavity (N = 19), and nasopharynx (n = 11). The median interval from completion of prior radiation to the diagnosis of recurrent disease was 35 months (range, 2-102 months). RESULTS: Re-irradiation improved 2-year overall survival, (32 % versus 11 %), progression-free survival (31 % versus 7 %), and local-regional control (39 % versus 3 %) compared to systemic therapy alone (p < 0.05, for both). The likelihood of developing any new grade 3+ toxicity was significantly higher among patients treated by re-irradiation compared to those treated by systemic therapy (53 % vs. 28 %, p < 0.001). There were 3 treatment-related fatalities, all of which occurred in the re-irradiation group. The incidence of grade 3+ late toxicity was 48 % and 12 % for patients in the re-irradiation and systemic therapy cohorts, respectively (p < 0.001). CONCLUSION: Although re-irradiation improved overall survival compared to systemic therapy for appropriately selected patients with local-regionally recurrent head and neck cancer, the relatively high risk of toxicity must be considered.

Severity of Financial Toxicity for Patients Receiving Palliative Radiation Therapy.

Introduction: Financial toxicity has negative implications for patient well-being and health outcomes. There is a gap in understanding financial toxicity for patients undergoing palliative radiotherapy (RT). Methods: A review of patients treated with palliative RT was conducted from January 2021 to December 2022. The FACIT-COST (COST) was measured (higher scores implying better financial well-being). Financial toxicity was graded according to previously suggested cutoffs: Grade 0 (score ≥26), Grade 1 (14-25), Grade 2 (1-13), and Grade 3 (0). FACIT-TS-G was used for treatment satisfaction, and EORTC QLQ-C30 was assessed for global health status and functional scales. Results: 53 patients were identified. Median COST was 25 (range 0-44), 49% had Grade 0 financial toxicity, 32% Grade 1, 15% Grade 2, and 4% Grade 3. Overall, cancer caused financial hardship among 45%. Higher COST was weakly associated with higher global health status/Quality of Life (QoL), physical functioning, role functioning, and cognitive functioning; moderately associated with higher social functioning; and strongly associated with improved emotional functioning. Higher income or Medicare or private coverage (rather than Medicaid) was associated with less financial toxicity, whereas an underrepresented minority background or a non-English language preference was associated with greater financial toxicity. A multivariate model found that higher area income (HR .80, P = .007) and higher cognitive functioning (HR .96, P = .01) were significantly associated with financial toxicity. Conclusions: Financial toxicity was seen in approximately half of patients receiving palliative RT. The highest risk groups were those with lower income and lower cognitive functioning. This study supports the measurement of financial toxicity by clinicians.

Integrating Overall Survival and Tumor Control Probability Models to Predict Local Progression After Brain Metastasis Radiosurgery.

Purpose: Stereotactic radiosurgery (SRS) for brain metastases is frequently prescribed to the maximum tolerated dose to minimize the probability of local progression. However, many patients die from extracranial disease prior to local progression and may not require maximally aggressive treatment. Recently, improvements in models of SRS tumor control probability (TCP) and overall survival (OS) have been made. We predicted that by combining models of OS and TCP, we could better predict the true risk of local progression after SRS than by using TCP modeling alone. Methods and Materials: Records of patients undergoing SRS at a single institution were reviewed retrospectively. Using established TCP and OS models, for each patient, the probability of 1-year survival [p(OS)] was calculated, as was the probability of 1-year local progression [p(LP)]) for each treated lesion. Joint-probability was used to combine the models [p(LP,OS)=p(LP)*p(OS)]. Analyses were conducted at the individual metastasis and whole-patient levels. Fine-Gray regression was used to model p(LP) or p(LP,OS) on the risk of local progression after SRS, with death as a competing risk. Results: At the patient level, 1-year local progression was 0.08 (95% CI, 0.03-0.15), median p(LP,OS) was 0.13 (95% CI, 0.07-0.2), and median p(LP) was 0.29 (95% CI, 0.22-0.38). At the metastasis level, 1-year local progression was 0.02 (95% CI, 0.01-0.04), median p(LP,OS) was 0.05 (95% CI, 0.02-0.07), and median p(LP) was 0.10 (95% CI, 0.07-0.13). p(LP,OS) was found to be significantly associated with the risk of local progression at the patient level (P = .048) and metastasis level (P = .007); however, p(LP) was not (P = .16 and P = .28, respectively). Conclusions: Simultaneous modeling of OS and TCP more accurately predicted local progression than TCP modeling alone. Better understanding which patients with brain metastases are at risk of local progression after SRS may help personalize treatment to minimize risk without sacrificing efficacy.

The Correlation Between Lymphocyte Nadir and Radiation Therapy for Soft Tissue Sarcoma: Defining Key Dosimetric Parameters and Outlining Clinical Significance.

Purpose: The objectives of this study were to identify key dosimetric parameters associated with postradiation therapy lymphopenia and uncover any effect on clinical outcomes. Methods and Materials: This was a retrospective review of 69 patients (between April 2010 and January 2023) who underwent radiation therapy (RT) as a part of curative intent for soft tissue sarcoma (STS) at a single academic institution. All patients with treatment plans available to review and measurable absolute lymphocyte count (ALC) nadir within a year after completion of RT were included. Results: Median follow-up was 22 months after the start of RT. A decrease in lymphocyte count was noted as early as during treatment and persisted at least 3 months after the completion of RT. On multivariable linear regression, the strongest correlations with ALC nadir were mean body dose, body V10 Gy, mean bone dose, bone V10 Gy, and bone V20 Gy. Five-year overall survival was 60% and 5-year disease-free survival was 44%. Advanced T-stage, chemotherapy use, use of intensity-modulated RT, lower ALC nadir, and the development of grade ≥2 lymphopenia at nadir were associated with worse overall survival and disease-free survival. Conclusions: Post-RT lymphopenia was associated with worse outcomes in STS. There were associations between higher body V10 Gy and bone V10 Gy and lower post-RT ALC nadir, despite the varying sites of STS presentation, which aligns with the well-known radiosensitivity of lymphocyte cell lines. These findings support efforts to reduce treatment-related hematopoietic toxicity as a way to improve oncologic outcomes. Additionally, this study supports the idea that the effect of radiation on lymphocyte progenitors in the bone marrow is more significant than that on circulating lymphocytes in treatments with limited involvement of the heart and lung.

The Impact of Local Control on Overall Survival after Y-90 Selective Internal Radiotherapy of Liver Metastases in Oligometastatic Cancer: A Retrospective Analysis.

Y-90 Selective Internal Radiotherapy (SIRT) is an ablative therapy used for inoperable liver metastasis. The purpose of this investigation was to examine the impact of local control after SIRT on overall survival (OS) in oligometastatic patients. A retrospective, single-institution study identified oligometastatic patients with ≤5 non-intracranial metastases receiving unilateral or bilateral lobar Y-90 SIRT from 2009 to 2021. The primary endpoint was OS defined from Y-90 SIRT completion to the date of death or last follow-up. Local failure was classified as a progressive disease at the target lesion(s) by RECIST v1.1 criteria starting at 3 months after SIRT. With a median follow-up of 15.7 months, 33 patients were identified who had a total of 79 oligometastatic lesions treated with SIRT, with the majority histology of colorectal adenocarcinoma (n = 22). In total, 94% of patients completed the Y-90 lobectomy. Of the 79 individual lesions treated, 22 (27.8%) failed. Thirteen patients received salvage liver-directed therapy following intrahepatic failure; ten received repeat SIRT. Median OS (mOS) was 20.1 months, and 12-month OS was 68.2%. Intralesional failure was associated with worse 1 y OS (52.3% vs. 86.2%, p = 0.004). These results suggest that intralesional failure following Y-90 may be associated with inferior OS, emphasizing the importance of disease control in low-metastatic-burden patients.

Consolidation Osimertinib Versus Durvalumab Versus Observation After Concurrent Chemoradiation in Unresectable EGFR-Mutant NSCLC: A Multicenter Retrospective Cohort Study.

INTRODUCTION: Durvalumab improves survival when used as consolidation therapy after chemoradiation (CRT) in patients with stage III NSCLC. The optimal consolidation therapy for patients with EGFR-mutant (EGFRmut) stage III NSCLC remains unknown. METHODS: In this multi-institutional, international retrospective analysis across 24 institutions, we evaluated outcomes in patients with stage III EGFRmut NSCLC treated with concurrent CRT followed by consolidation therapy with osimertinib, durvalumab, or observation between 2015 and 2022. Kaplan-Meier method was used to estimate real-world progression-free survival (rwPFS, primary end point) and overall survival (secondary end point). Treatment-related adverse events (trAEs) during consolidation treatment were defined using Common Terminology Criteria for Adverse Events version 5.0. Multivariable Cox regression analysis was used. RESULTS: Of 136 patients with stage III EGFRmut NSCLC treated with definitive concurrent CRT, 56 received consolidation durvalumab, 33 received consolidation osimertinib, and 47 was on observation alone. Baseline characteristics were similar across the three cohorts. With a median follow-up of 46 months for the entire cohort, the median duration of treatment was not reached (NR) for osimertinib (interquartile range: NR-NR) and was 5.5 (interquartile range: 2.4-10.8) months with durvalumab. After adjusting for nodal status, stage III A/B/C, and age, patients treated with consolidation osimertinib had significantly longer 24-month rwPFS compared to those treated with durvalumab or in the observation cohorts (osimertinib: 86%, durvalumab: 30%, observation: 27%, p < 0.001 for both comparisons). There was no difference in rwPFS between the durvalumab and the observation cohorts. No significant difference in overall survival across the three cohorts was detected, likely due to the limited follow-up. Any-grade trAE occurred in 52% (2 [6.1%] grade ≥3) and 48% (10 [18%] grade ≥3) of patients treated with osimertinib and durvalumab, respectively. Of 45 patients who progressed on consolidation durvalumab, 37 (82%) subsequently received EGFR tyrosine kinase inhibitors. Of these, 14 (38%) patients developed trAEs including five patients with pneumonitis (14%; 2 [5.4%] grade ≥3) and five patients with diarrhea (14%; 1 [2.7%] grade ≥3). CONCLUSIONS: This study suggests that among patients with stage III unresectable NSCLC with a sensitizing EGFR mutation, consolidation osimertinib was associated with a significantly longer rwPFS compared to durvalumab or observation. No unanticipated safety signals were observed with consolidation osimertinib.

Outcomes after endovascular abdominal aortic aneurysm repair are equivalent between genders despite anatomic differences in women.

OBJECTIVE: Prior work confirms gender-specific anatomic differences in patients undergoing endovascular aneurysm repair, but the clinical implications remain ill defined. The purpose of this study was to compare gender-specific early outcomes after endovascular aneurysm repair using a large international registry. METHODS: Over the 2-year period ending in 2011, 1,262 patients (131 women, 10.4%; 1,131 men, 89.6%) with infrarenal aneurysms treated with the Endurant stent graft were prospectively enrolled in the ENGAGE registry and followed clinically and radiographically. RESULTS: Women were older (75.5 ± 7.0 vs 72.8 ± 8.1; P = .0003) and had smaller aneurysms (57.8 ± 9.5 vs 60.6 ± 11.9 mm; P = .01). Women's infrarenal aortic necks were of narrower diameter (21.8 ± 3.4 vs 24.0 ± 3.5 mm; P < .0001), shorter length (24.3 ± 11.8 vs 27.3 ± 12.4 mm; P = .009), and greater angulation (37.7 ± 26.2° vs 29.4 ± 23.3°; P = .0002). More women had an infrarenal neck angle >60° (19.2% vs 9.1%; P = .001). Technical success was achieved in equal numbers of women and men (97.7% vs 99.2%; P = .10). On completion angiography, the incidence of any endoleak (21.5% vs 15.4%; P = .08) and type I endoleak (1.5% vs 1.1%; P = .60) did not differ between genders. At the 1-month follow-up, there were no differences between women and men with respect to endograft occlusion (2.5% vs 1.9%; P = .70), and differences observed in any endoleak (17.2% vs 11.4%; P = .08) and type I endoleaks (3.3% vs 1.2%; P = .08) did not reach statistical significance. Freedom from major adverse events was similar for women and men at 30 days (98.5% vs 95.8%; P = .23) and 1 year (85% vs 89.8%; P = .40). Survival at 30 days (100% vs 98.6%) and 1 year (92.5% vs 91.6%; P = .99) was similar for women and men. CONCLUSIONS: This large multinational registry confirms the previously observed prevalence of suboptimal neck anatomy in women. Even though women have shorter and more angulated infrarenal necks, their technical outcomes at 30 days and clinical outcomes at 1 year were similar to those of men. Much longer follow-up is necessary to determine whether these outcomes proved durable.

Technical factors are strongest predictors of postoperative renal dysfunction after open transperitoneal juxtarenal abdominal aortic aneurysm repair.

OBJECTIVE: Juxtarenal abdominal aortic aneurysms (AAAs) have predominantly been repaired using an open technique. We present a series of patients with juxtarenal AAAs and analyze multiple factors predictive of postoperative renal dysfunction. METHODS: Between March 2000 and September 2011, all patients in our prospectively maintained database undergoing juxtarenal AAA repair were evaluated for demographics, operative details, and in-hospital outcomes. Postoperative renal dysfunction was classified using the RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria (glomerular filtration rate decrease >25%). The relationship between perioperative factors and postoperative renal dysfunction was explored using both univariate and multivariate analysis (logistic regression). RESULTS: Of 169 patients, 76 (45%) required clamping above one renal artery, whereas 93 patients (55%) required clamping above both renal arteries. Mean (standard deviation) renal ischemia time was 29.2 (8.9) minutes (range, 12-65 minutes). Twenty-seven patients (16%) underwent adjunctive renal procedures, 19 (11.3%) required left renal vein division, and 130 (76.9%) received intraoperative mannitol. Postoperative renal dysfunction occurred in 63 patients (37.3%), with the majority (69%) resolving during hospital stay. Seven patients (4.1%) required postoperative dialysis, which was permanent in two cases. Patients who developed postoperative renal dysfunction had significantly longer mean renal ischemia times (34.7 [9.3] minutes vs 25.9 [6.6] minutes; P < .001), a higher rate of bilateral suprarenal aortic clamping (68.3% vs 47.2%; P = .008), higher rates of adjunctive renal artery procedures (26.7% vs 8.8%; P = .002), and higher rates of left renal vein division (20.6% vs 5.7%; P = .003). Logistic regression identified left renal vein division, renal ischemia time, and aortic clamp position as the strongest predictors of renal dysfunction. The use of mannitol was seen to be protective. Overall in-hospital mortality was 4.1% and was 9.5% among patients with postoperative renal dysfunction. CONCLUSIONS: Postoperative transient renal dysfunction occurred in 37.3% of patients after open juxtarenal AAA repair, with a low incidence of dialysis and a low rate of permanent dysfunction. Technical factors including renal ischemia time, aortic clamp position, and left renal vein division are the strongest predictors of renal dysfunction. The use of intraoperative mannitol was associated with decreased postoperative renal dysfunction.

Primary squamous cell carcinoma of the vagina: prognostic factors, treatment patterns, and outcomes.

OBJECTIVE: Primary squamous cell carcinoma (SCCA) of the vagina is a rare malignancy with limited data to guide treatment. We evaluated prognostic factors and outcomes for patients with primary vaginal SCCA treated with definitive radiation therapy at a single institution. METHODS: A retrospective analysis was performed on patients treated for primary vaginal SCCA from 1959 to 2011. RESULTS: Ninety-one patients with primary vaginal SCCA were treated with definitive radiation therapy. Thirty-eight patients had FIGO stage I, 28 stage II, 13 stage III, and 12 stage IV disease. The mean total dose was 70.1 Gy. Two-year overall survival (OS), locoregional control rate (LRC), and distant metastasis-free survival by stage were, respectively: stage I: 96.2%, 80.6%, 87.5%; stage II: 92.3%, 64.7%, 84.6%; stage III: 66.6%, 44.4%, 50.0%; and stage IV: 25.0%, 14.3%, 25.0%. Treatment with total dose over 70 Gy was associated with improved OS (p=0.0956) and LRC (p=0.055). There was a significant difference in median dose received by patients who developed grade 3/4 toxicity compared to those who did not (82.9 Gy versus 70.0 Gy, p=0.0019). None of the 10 patients treated with IMRT experienced locoregional recurrence or grade 3/4 toxicity. Tumor size larger than 4 cm was associated with worse OS (p=0.0034) and LRC (p=0.006). CONCLUSIONS: Our analysis suggests that the optimal dose for definitive treatment of SCCA of the vagina lies between 70 and 80 Gy. Treatment with IMRT may allow for dose escalation with reduced toxicity and excellent LRC. Tumor size over 4 cm is associated with inferior outcomes and may require additional treatment modalities.

Understanding surgical preference and practice in hemodialysis vascular access creation.

Understanding healthcare providers' preferences, values, and beliefs around AVF eligibility is important to explain variability in practice. We conducted a survey of international surgeons, using hypothetical patient scenarios, to assess resources used, variables, perceived barriers, and absolute contraindications to access creation. A total of 134 surgeons completed the survey. Venous duplex ultrasound mapping (VDUM) was offered to all patients by 90% of US, 68% Canadian, and 63% European respondents. VDUM altered clinical decision less than 25% of the time for 33% American, 48% Canadian, and 85% European surgeons. Increased comorbidities and previous failed access were deterrents to AVF creation as was vessel size. Second choice access was the AV graft in the US and Europe and the catheter in Canada. Absolute contraindications to AVF creation included patient life expectancy <1 year, left ventricular ejection fraction (LVEF) <15%, and a history of dementia, while 42% surgeons reported no absolute contraindications. Perceived barriers included patient preferences, long wait times for surgery, and late referral to a Nephrologist. Significant variability exists in the surgical preoperative assessment of patients, and the eligibility criteria used for fistula creation. Understanding surgeons' preferences can aid in establishing standardization for VA access eligibility, including surgical assessment.