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A series of laboratory experiments were conducted to study the fate and transport of Toxoplasma gondii oocysts in soils as a function of soil physicochemical properties and soil water chemistry properties. Soil columns were homogeneously packed with loamy sand soils (Lewiston and Greenson series) and sandy loam soils (Sparta and Gilford series), and subject to hydrologic conditions characterized by the absence and presence of an anionic surfactant-Aerosol 22 in the artificial rainfall. Quantitative polymerase chain reaction (qPCR) was utilized for the detection and enumeration of oocysts in soil leachates to evaluate their breakthrough and in soil matrices to examine their spatial distribution. Differences in the rate and extent of transport of oocysts were observed as a function of physical and chemical parameters tested. The breakthrough of oocysts was observed for all the soils irrespective of the presence of surfactant. However, in the absence of surfactant, the predominant fate of oocysts in soils subject to simulated rainfall was their retention in the soil profile. The presence of surfactant induced a change in the fate of oocysts in these soils exposed to rainfall simulation as the predominant fate of oocysts was found to be in the soil leachates., (© 2023 The Authors. Environmental Microbiology Reports published by Applied Microbiology International and John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: The identification of biomarkers to select patients with metastatic renal cell carcinoma (mRCC) most likely to respond to combination immunotherapy (IO) is needed. We sought to investigate an association of the baseline neutrophil-to-eosinophil ratio (NER) with outcomes to nivolumab plus ipilimumab for patients with mRCC., Methods: We performed a retrospective review of patients with clear cell mRCC treated with nivolumab plus ipilimumab from Vanderbilt-Ingram Cancer Center and Duke Cancer Institute. Patients with prior receipt of immunotherapy and those without available baseline complete blood count with differential were excluded. Patients were divided into groups by the median baseline NER and analyzed for overall survival (OS), progression free survival (PFS), and objective response rate (ORR). Patients were also divided by median baseline neutrophil-to-lymphocyte ratio (NLR) and analyzed for clinical outcome. Further analyses of patients above/below the median NER and NLR were performed in subgroups of IMDC intermediate/poor risk, IMDC favorable risk, and treatment naïve patients., Results: A total of 110 patients were included: median age was 61 years and 75% were treatment naïve. The median NER (mNER) at baseline was 26.4. The ORR was 40% for patients with mNER (OR 2.39, p = 0.04). The median PFS for patients with mNER (HR 0.50, p < 0.01). Median OS was not reached (NR) for patients with mNER (HR 0.31, p < 0.01). The median NLR (mNLR) was 3.42. While patients with mNLR group., Conclusions: A lower baseline NER was associated with improved clinical outcomes (PFS, OS, and ORR) in patients with mRCC treated with nivolumab plus ipilimumab, and prospective validation of the baseline NER as a predictive biomarker for response to immunotherapy-based combinations in mRCC is warranted., (© 2021. The Author(s).)

The combination of ipilimumab plus nivolumab (I+N) has greatly improved outcomes in patients with intermediate or poor-risk untreated metastatic renal cell carcinoma (mRCC). However, little is known about the outcomes of patients with brain metastasis (BrM) treated with I+N. A search was performed to retrospectively identify all patients with mRCC treated with I+N in the Duke Cancer Institute and the Cleveland Clinic Taussig Cancer Center, followed by a chart review. Patients were included if they had BrM at the time of I+N initiation. Cohort characteristics are summarized with descriptive statistics. Kaplan-Meier method was used to estimate overall survival (OS) and global, intracranial, and extracranial progression-free survival (PFS) for the cohort and log rank test was used to compare OS and PFS between patient groups. Radiographic response was categorized by RECIST. Fisher's exact test was used to correlate patient factors with radiographic response. From October 2017 to December 2020, 19 patients with BrM received I+N for mRCC with a median follow-up time of 27.1 months (range 15.0-35.6). By International Metastatic RCC Database Consortium (IMDC) risk criteria, 16% had favorable, 58% had intermediate, and 26% had poor-risk disease. 68% were systemic therapy naïve, and 77% of patients had clear cell histology. 95% had received local CNS directed therapy with surgery, radiotherapy, or both. The objective response rate was 44% (0% complete response) with three of six patients treated in the second line or greater setting experiencing a partial response. The median PFS was 7.6 months (95% CI 5.6 to 14.9). The median extracranial PFS was 8.5 months (95% CI 5.6 to 19.7), and median intracranial PFS was 14.7 months (95% CI 7.2 to not reached). No variables assessed were significantly associated with radiographic response (gender, IMDC risk, presence of bone metastasis, line of therapy, or presence of immune related adverse events). In our retrospective cohort of patients with mRCC with BrM, I+N, in combination with CNS-directed local therapy, appears to have clinical efficacy as previously described with responses seen beyond the first-line setting. Further investigation is warranted in this population given exclusion from prior clinical trials., Competing Interests: Competing interests: LCB declares the following relationships: consulting with Seattle Genetics. KD declares the following relationship: consulting with Tyra BioSciences. WW declares that he has no conflicts of interest that might be relevant to the contents of this manuscript. EK declares that she has no conflicts of interest that might be relevant to the contents of this manuscript. CK declares that he has no conflicts of interest that might be relevant to the contents of this manuscript. DG declares the following relationships: Acerta Pharmaceuticals—Research, American Association for Cancer Research—Sr Editor, Astellas—Consultant, Research, Advisory Board, Astrazeneca—Consultant, Advisory Board, Axess Oncology—Independent Contractor, Bayer H/C Pharmaceuticals—Research, Consultant, Speaker, Honorarium, Travel accommodations, SC, BMS—Consultant, Research, Steering Committee, Calithera—Research, Capio Biosciences—Scientific Advisory Board, EMD Serono—Honorarium, Exelixis—Research, Consultant, Speaker, Honorarium, Travel accommodations, Flatiron—Consultant, Ipsen—Honorarium, Janssen Pharmaceuticals—Research, Consultant, Independent Data Monitoring Committee (IDMC), Leidos Biomedical Research—Consultant, Merck Sharp & Dohme—Consultant, Michael J Hennessey Associates—Honorarium, Consultant, Millennium Medical Publishing, Clinical Advances in Hematology & Oncology—Co-Editor-in-Chief, Modra Pharmaceuticals B.V.—Advisory Board, Myovant Sciences—Consultant, Nektar Therapeutics—Steering Committee, Novartis—Research, Physician Education Resource—Consultant, Pfizer—Research, Consultant, Steering Committee, Honorarium, Sanofi—Research, Consultant, Speaker, Honorarium, Travel accommodations, UroGPO—Honorarium, UroToday—Honorarium, Travel accommodations, Vizuri Health Sciences—Consultant, NCI—Steering Committee. BR declares the following relationships: Research funding (to Vanderbilt University) from Pfizer, Hoffman-LaRoche, Incyte, AstraZeneca, Taris, Seattle Genetics, Arrowhead Pharmaceuticals, Immunomedics, BMS, Mirati Therapeutics, Merck, Surface Oncology, Dragonfly Therapeutics, Aravive and Exelixis; Consulting with Bristol Myer Squibb, Pfizer, Roche/Genentech, Aveo, Synthorx, Compugen, Merck, Corvus, Surface Oncology, 3DMedicines, Aravive, Alkermes, Arrowhead, GSK, Shionogi, Eisai. Stock ownership in PTC Therapeutics. MCO declares the following relationships: Consulting with BMS, Merck, Pfizer, Aveo, Exelixis and Eisai. TZ declares the following relationships: Research funding (to Duke University) from Pfizer, Janssen, Acerta, Abbvie, Novartis, Merrimack, OmniSeq, PGDx, Merck, Mirati, Astellas and Genentech; Speaking with Genomic Health and Sanofi Aventis; Consulting with AstraZeneca, Bayer, Pfizer, Foundation Medicine, Janssen, Merck, Amgen, MJH Associates, and BMS. Stock ownership/employment (spouse) from Capio Biosciences, Archimmune Therapeutics and Nanorobotics., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Two separate antiangiogenic tyrosine kinase inhibitors (TKIs) and immunotherapy (IO) combinations are FDA-approved as front-line treatment for metastatic renal cell carcinoma (mRCC). Little is known about off-protocol and post-front-line experience with combination TKI-IO approaches., Methods: We conducted a retrospective analysis of mRCC patients who received combination TKI-IO post-first-line therapy between November 2015 and January 2019 at MD Anderson Cancer Center and Duke Cancer Institute. Chart review detailed patient characteristics, treatments, toxicity, and survival. Independent radiologists, blinded to clinical data, assessed best radiographic response using RECIST v1.1., Results: We identified 48 mRCC patients for inclusion: median age 65 years, 75.0% clear cell histology, 68.8% IMDC intermediate risk, and median two prior systemic therapies. TKI-IO combinations included nivolumab-cabozantinib (N +C; 24 patients), nivolumab-pazopanib (N+P; 13), nivolumab-axitinib (6), nivolumab-lenvatinib (2), and nivolumab-ipilimumab-cabozantinib (3). The median progression-free survival was 11.6 months and the median overall survival was not reached. Response data were available in 45 patients: complete response (CR; n = 3, 6.7%), partial response (PR; 20, 44.4%), stable disease (SD; 19, 42.2%), and progressive disease (3, 6.7%). Overall response rate was 51% and disease control rate (CR+PR+SD) was 93%. Only one patient had a grade ≥3 adverse event., Conclusion: To our knowledge, this is the first case series reporting off-label use of combination TKI-IO for mRCC. TKI-IO combinations, particularly N+P and N+C, are well tolerated and efficacious. Although further prospective research is essential, slow disease progression on IO or TKI monotherapy may be safely controlled with addition of either TKI or IO., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Patient selection is critical to determine who benefits from initial cytoreductive nephrectomy and who benefits from initial systemic treatment. Cytoreductive nephrectomy can no longer be considered a one-size-fits-all approach. Multidisciplinary evaluation is key., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: In recent years, the treatment options for metastatic hormone-sensitive prostate cancer (mHSPC) have expanded significantly. In addition to androgen deprivation therapy, the systemic treatments now include docetaxel, abiraterone, enzalutamide, and apalutamide. Radiation to the primary is also an option for select low-volume patients., Methods: We conducted a review of the pivotal trials that have changed the practice of mHSPC., Results: We describe an overview of the trials that investigated docetaxel (CHAARTED and STAMPEDE-Docetaxel), abiraterone (LATTITUDE and STAMPEDE-Abiraterone), enzalutamide (ARCHES, ENZAMET), apalutamide (TITAN), and radiation to the primary (STAMPEDE-Radiation)., Discussion: The treatment of mHSPC is a complex topic, and treatment choice should be individualized. Patient preferences, cost, volume of disease, and side effect profiles are important in determining which option is the best for an individual patient.

Purpose: The purpose of this study is to identify predictors of tumor-positive surgical margins after breast-conserving surgery on dynamic contrast-enhanced (DCE) MRI., Materials and Methods: We conducted a retrospective study of consecutive women who underwent DCE MRI before breast-conserving surgery from 2005 to 2014. Patient demographics, indication for surgery, MRI findings, biopsy pathology results, and surgical outcomes were reviewed. The unpaired t-test and chi-square test were used to compare the positive and negative margins groups., Results: 554 women (mean age, 56; range, 26-90) underwent DCE MRI before 575 breast-conserving surgeries for invasive carcinoma (n = 473) or ductal carcinoma in situ (DCIS) (n = 102). Positive margins requiring re-excision occurred in 19.7% (93/473) of surgeries for invasive carcinoma and 31.4% (32/102) of surgeries for DCIS. For invasive carcinoma surgeries, positive margins were more common when MRI demonstrated the finding of non-mass enhancement (NME) rather than the finding of enhancing mass (33.8% [22/65] versus 16.9% [61/360], p < 0.01). Tumor size on MRI was significantly larger in the positive margins group (2.5 cm versus 1.9 cm, p < 0.001). Positive margins were more common with invasive lobular rather than invasive ductal histology at core biopsy (38.3% [18/47] versus 16.0% [56/350], p < 0.001). For DCIS surgeries, there were no significant differences in positive margin rates related to MRI features., Conclusion: For invasive carcinoma surgeries, positive margins are associated with NME on MRI, larger tumor size on MRI, and lobular histology at core biopsy. These findings may be used to predict which patients are at risk for positive margins after breast-conserving surgery., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Immune checkpoint inhibitors have dramatically changed the prognosis for patients with metastatic melanoma. However, not all patients respond to therapy and toxicities can be severe leaving need for reliable clinical predictive markers., Methods: We examined primary tumor characteristics including ulceration, BRAF mutation status, and Breslow depth in patients who subsequently developed stage IV disease and were treated with ipilimumab at 3 institutions. Patients in this study were not treated on clinical trials. To investigate the relationship between patient characteristics at the time of diagnosis and survival following melanoma diagnosis we utilized Cox proportional hazards models, accounting for delayed entry into the study cohort. Cox models estimate the age and institution adjusted hazard ratios for risk of death., Results: Of patients (n=385) treated with ipilimumab for stage IV melanoma, 302 met inclusion criteria. The complete response to ipilimumab was 5%, partial response was 13%, 18% had stable disease, 62% had progressive disease, and 5 unknown. The median overall survival rate was 2.03 years [95% confidence interval (CI): 0.13, 3.05]. Primary tumor Breslow depth, lymphovascular invasion, BRAF status, and ulceration did not predict sensitivity to ipilimumab. In this study patient cohort, BRAF mutation (adjusted hazard ratio: 1.43, 95% CI: 0.98, 2.07) and presence of ulceration (adjusted hazard ratio: 1.47, 95% CI: 0.95, 2.26) contributed to an increased risk of death., Conclusions: The presence of ulceration did not correlate with sensitivity to ipilimumab. Ulceration of the primary tumor and a BRAF mutation were moderately associated with worse survival in patients with metastatic melanoma treated with ipilimumab.

Objective: The objective of our study was to determine the risk of malignancy associated with architectural distortion and to evaluate the imaging and clinical features that may contribute to the prediction of malignancy in the setting of architectural distortion., Materials and Methods: We performed a retrospective review of architectural distortion cases from January 1, 2004, to December 31, 2013. Imaging findings and pathology outcomes were reviewed., Results: Over the 10-year study period, architectural distortion that was considered to be suspicious for or highly suggestive of malignancy was present in 435 of 231,051 (0.2%) mammographic examinations. Cases were excluded if the main finding described was a mass with an associated feature of architectural distortion (n = 62) or if no pathology results were available (n = 4). Two hundred seventy-five cases of invasive adenocarcinoma or ductal carcinoma in situ (DCIS) were identified; the positive predictive value (PPV) was therefore 74.5% (275/369). DCIS alone was identified in only 4.1% (15/369). The most common benign finding on pathology was a radial scar or complex sclerosing lesion (27/369, 7.3%). Architectural distortion was less likely to represent malignancy on screening mammography than on diagnostic mammography (67.0% vs 83.1%, respectively; p < 0.001). Architectural distortion without a sonographic correlate was less likely to represent malignancy than architectural distortion with a correlate (27.9% vs 82.9%, respectively; p < 0.001). There was no statistically significant difference in the malignancy rate between pure architectural distortion and architectural distortion with calcifications or asymmetries (73.0% vs 78.8%; p = 0.26)., Conclusion: The PPV of architectural distortion for malignancy is 74.5%. Architectural distortion is less likely to represent malignancy if detected on screening mammography than on diagnostic mammography or if there is no sonographic correlate.

Background: Low-income women have the lowest rates of breastfeeding in the United States. Greater understanding of factors that predict intention to feed artificial breastmilk substitute is needed to inform the design and timing of interventions to promote breastfeeding among vulnerable women. This study aimed to identify demographic and reproductive characteristics and other factors associated with intent to feed artificial breastmilk substitute among low-income women., Materials and Methods: Data from 520 low-income women interviewed at 24-41 weeks of gestation during enrollment in a prenatal breastfeeding education intervention study were analyzed. Participant characteristics, reasons for feeding decision, and sources and types of information received were compared among women intending to feed only artificial breastmilk substitute and other women., Results: Most participants (95%) had already chosen an infant feeding method at the time of interview. There were no differences in plans to return to work by feeding plan. Women reporting intention to feed only artificial breastmilk substitute were less likely to report receiving information about the benefits of breastfeeding, how to breastfeed, and pumps and were more likely to cite personal preference and convenience as reasons for their decision. Women were more likely to intend to feed artificial breastmilk substitute if they had a previous live birth or had not breastfed a child, including the most recent., Conclusions: These findings suggest breastfeeding promotion should target women early and include sensitive, effective ways to promote breastfeeding among women who have not previously successfully breastfed. Breastfeeding history should be elicited, and plans to pump should be supported prenatally.

Purpose: Report on the anatomic qualification of the snuffbox radial artery (SBRA) and proximal radial artery (PRA) for pAVF.
, Methods: Retrospective analysis of upper extremity mapping in 64 limbs in 55 dialysis patients was performed. The radial artery was assessed for diameter, patency, flow and proximity to the adjacent vein to SBRA and PRA. Sites qualified for pAVF on a binary basis when the in situ radial artery and adjacent vein were straight, parallel, greater than 2 mm in diameter and within 1.5 mm of each other. Effect of age, sex, diabetes, systolic blood pressure and obesity were assessed with logistic regression. Mean, median and frequency distribution of vessel diameter and distance were analyzed.
, Results: Radial artery sites were qualified for pAVF in 47.6% (30/63) at the SBRA and 87.9% (29/33) at the PRA. SBRA sites were disqualified for vessel size in 36.4% (12/33 overall, usually vein 11/12), distance in 24% (8/33) and both 36.4% (12/33). All (4/4) PRA sites were disqualified for vessel size alone. The adjacent vein was the median vein or cephalic vein for the SBRA, and the perforating vein or vena comitans for the PRA. Effects of age, sex, diabetes, systolic blood pressure, obesity and prior fistula did not attain statistical significance.
, Conclusions: Most dialysis patients meet the anatomic requirements for pAVF in the SBRA or PRA. Vessel size is the most common limiting variable followed by distance between vessels.