Publications by authors named "C Veronica Smith"

17,586 Publications

Phase II trial of the IDO pathway inhibitor indoximod plus pembrolizumab for the treatment of patients with advanced melanoma.

J Immunother Cancer 2021 Jun;9(6)

University of Iowa Holden Comprehensive Cancer Center, Iowa City, Iowa, USA.

Background: The indoleamine 2,3-dioxygenase (IDO) pathway is a key counter-regulatory mechanism that, in cancer, is exploited by tumors to evade antitumor immunity. Indoximod is a small-molecule IDO pathway inhibitor that reverses the immunosuppressive effects of low tryptophan (Trp) and high kynurenine (Kyn) that result from IDO activity. In this study, indoximod was used in combination with a checkpoint inhibitor (CPI) pembrolizumab for the treatment for advanced melanoma.

Methods: Patients with advanced melanoma were enrolled in a single-arm phase II clinical trial evaluating the addition of indoximod to standard of care CPI approved for melanoma. Investigators administered their choice of CPI including pembrolizumab (P), nivolumab (N), or ipilimumab (I). Indoximod was administered continuously (1200 mg orally two times per day), with concurrent CPI dosed per US Food and Drug Administration (FDA)-approved label.

Results: Between July 2014 and July 2017, 131 patients were enrolled. (P) was used more frequently (n=114, 87%) per investigator's choice. The efficacy evaluable population consisted of 89 patients from the phase II cohort with non-ocular melanoma who received indoximod combined with (P).The objective response rate (ORR) for the evaluable population was 51% with confirmed complete response of 20% and disease control rate of 70%. Median progression-free survival was 12.4 months (95% CI 6.4 to 24.9). The ORR for Programmed Death-Ligand 1 (PD-L1)-positive patients was 70% compared with 46% for PD-L1-negative patients. The combination was well tolerated, and side effects were similar to what was expected from single agent (P).

Conclusion: In this study, the combination of indoximod and (P) was well tolerated and showed antitumor efficacy that is worth further evaluation in selected patients with advanced melanoma.
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http://dx.doi.org/10.1136/jitc-2020-002057DOI Listing
June 2021

Valve Sparing Root Replacement versus Bio-Bentall: Inverse Propensity Weighting of 796 Patients.

Ann Thorac Surg 2021 Jun 8. Epub 2021 Jun 8.

Columbia University Vagelos College of Physicians and Surgeons, New York, NY; Division of Cardiothoracic and Vascular Surgery, New York Presbyterian Hospital, Columbia University Medical Center, New York, NY. Electronic address:

Background: This large cohort, single center study aims to compare the 10-year survival and freedom from aortic valve reintervention between valve sparing root replacement (VSRR) and bioprosthetic Bentall (bio-Bentall).

Methods: All patients undergoing elective VSRR or bio-Bentall for aortic root aneurysm between March 2005 through October 2019 were retrospectively reviewed (n=796 [VSRR = 360]). Inverse probability of treatment weighting (IPTW) balanced clinical variables between groups. Mean follow-up was 58.0 +/- 45.4 (range 0-167) months.

Results: After IPTW adjustment, 10-year survival did not differ between groups (VSRR: 87.0% vs bio-Bentall: 92.7%, p=0.780). Cumulative incidence of aortic valve reintervention was 5.9% for VSRR (95% CI, 2.9%-10.4%) and 10.6% for bio-Bentall (95% CI, 6.2%-16.4%, p=0.798). Fine and Gray computing risk regression model identified age at surgery (sHR 0.97, 95% CI, 0.95-0.99, p=0.015), body surface area (sHR 6.21, 95% CI, 1.97-19.59, p=0.002) and bicuspid aortic valve (sHR 2.15, 95% CI, 1.04-4.44, p =0.038) as independently associated with aortic valve reintervention. For patients ≤50-year-old, cumulative incidence of aortic valve reintervention was 16.2% for VSRR (95% CI, 7.0%-28.8%) and 17.8% for bio-Bentall (95% CI, 6.9%-32.8%)(p=0.363).

Conclusions: VSRR and bio-Bentall show similar excellent survival and freedom from aortic reintervention rates up to 10 years; however, a durable valve solution for young patients with bicuspid aortic valve remains a challenge.
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http://dx.doi.org/10.1016/j.athoracsur.2021.05.044DOI Listing
June 2021

Chickens, Sex, and Revisiting an Old Paradigm.

Endocrinology 2021 Jul;162(7)

Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3168, Australia.

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http://dx.doi.org/10.1210/endocr/bqab106DOI Listing
July 2021

Assessing the impact of multiple ultraviolet disinfection cycles on N95 filtering facepiece respirator integrity.

Sci Rep 2021 Jun 10;11(1):12279. Epub 2021 Jun 10.

Department of Civil and Resource Engineering, Centre for Water Resources and Studies, Dalhousie University, 1360 Barrington St., Halifax, NS, B3H 4R2, Canada.

During the COVID-19 pandemic, N95 filtering facepiece respirators (FFRs) were recommended to protect healthcare workers when providing care to infected patients. Despite their single-use disposable nature, the need to disinfect and repurpose FFRs is paramount during this global emergency. The objectives of this study were to (1) determine if UV treatment has an observable impact on respirator integrity; (2) test the impact of UV treatment on N95 FFR user fit; and (3) test the impact of UV treatment on FFR integrity. Ultraviolet (UV) disinfection was assessed in maintaining N95 FFR integrity. Two models of FFRs were exposed to UV fluences ranging from 0 to 10,000 mJ cm per side and subsequently tested for fit, respirator integrity, and airflow. Inspection of N95 FFRs before and after UV treatment via microscopy methods showed no observable or tactile abnormalities in the integrity of respirator material or straps. Tensile loading tests on UV-treated and untreated respirator straps also demonstrated no impact on breaking strength. Standardized fit test methods showed no compromise in user fit following UV treatment. Evaluation of particle penetration and airflow through N95 FFRs showed no impact on integrity, and average filtration efficiency did not fall below 95% for any of the respirator types or fluence levels. This work provides evidence that UV disinfection does not compromise N95 FFR integrity at UV fluences up to 10,000 mJ cm. UV disinfection is a viable treatment option to support healthcare professionals in their strategy against the spread of COVID-19.
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http://dx.doi.org/10.1038/s41598-021-91706-1DOI Listing
June 2021

A genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor.

PLoS Genet 2021 Jun 10;17(6):e1009577. Epub 2021 Jun 10.

Shoulder Unit, Princess Elizabeth Orthopaedic Centre, Royal Devon and Exeter Hospital, Exeter, United Kingdom.

Frozen shoulder is a painful condition that often requires surgery and affects up to 5% of individuals aged 40-60 years. Little is known about the causes of the condition, but diabetes is a strong risk factor. To begin to understand the biological mechanisms involved, we aimed to identify genetic variants associated with frozen shoulder and to use Mendelian randomization to test the causal role of diabetes. We performed a genome-wide association study (GWAS) of frozen shoulder in the UK Biobank using data from 10,104 cases identified from inpatient, surgical and primary care codes. We used data from FinnGen for replication and meta-analysis. We used one-sample and two-sample Mendelian randomization approaches to test for a causal association of diabetes with frozen shoulder. We identified five genome-wide significant loci. The most significant locus (lead SNP rs28971325; OR = 1.20, [95% CI: 1.16-1.24], p = 5x10-29) contained WNT7B. This variant was also associated with Dupuytren's disease (OR = 2.31 [2.24, 2.39], p<1x10-300) as were a further two of the frozen shoulder associated variants. The Mendelian randomization results provided evidence that type 1 diabetes is a causal risk factor for frozen shoulder (OR = 1.03 [1.02-1.05], p = 3x10-6). There was no evidence that obesity was causally associated with frozen shoulder, suggesting that diabetes influences risk of the condition through glycemic rather than mechanical effects. We have identified genetic loci associated with frozen shoulder. There is a large overlap with Dupuytren's disease associated loci. Diabetes is a likely causal risk factor. Our results provide evidence of biological mechanisms involved in this common painful condition.
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http://dx.doi.org/10.1371/journal.pgen.1009577DOI Listing
June 2021