Citations

Mayo Clinic

Clear

1172 citation(s) found for "Ma, Cynthia".

Establishing a SARS-CoV-2 (COVID-19) Drive-Through Collection Site: A Community-Based Participatory Research Partnership With a Federally Qualified Health Center
Woods, Cynthia , Patel, Aarti , Weis, Jennifer A., Abbenyi, Adeline, Sia, Irene G. , Berbari, Elie F. , Crane, Sarah J. , Brewer, LaPrincess C. , Weis, Jennifer, Brockman, Tabetha A. , Berbari, Elie, Crane, Sarah, Doubeni, Chyke A. , Sia, Irene G , Jones, Clarence

American Journal of Public Health | February 18, 2021 | Volume: 111 | Issue: 4 | Pages: 658-662

10.2105/ajph.2020.306097 | PMID 33600248 Get It

The COVID-19 pandemic has disproportionately affected underserved and minority populations in the United States. This is partially attributable to limited access to diagnostic testing from deeply rooted structural inequities precipitating higher infection and mortality rates. We describe the process of establishing a drive-through collection site by leveraging an academic–community partnership between a medical institution and a federally qualified health center in Minnesota. Over 10 weeks, 2006 COVID-19 tests were provided to a socioeconomically disadvantaged population of racial/ethnic minorities and low-income essential workers.
Abstract PD2-10: Validation of a predictive model for potential response to neoadjuvant endocrine therapy (NET) in postmenopausal women with clinical stage II or III estrogen receptor positive (ER+) and HER2 negative (HER2-) breast cancer (BC): An ALTERNAT
Leitch, A. Marilyn , Sanati, Souzan , Unzeitig, Gary, Hahn, Olwen, Guenther, Joseph M., Caudle, Abigail S. , Crouch, Erika C., Maluf, Horacio , Tiersten, Amy , Mita, Monica , Razaq, Wajeeha, Dockter, Travis , Zujewski, Jo Anne , Weiss, Anna , Hudis, Clifford A. , Cynthia, X. , Ellis, Matthew J. , Suman, Vera J. , Vij, Kiran R , Hoog, Jeremy , Watson, Mark A. , Dowsett, Mitch , Hieken, Tina J. , Wang, Yang , Winer, Eric P. , Hunt, Kelly K. , Partridge, Ann H. , Carey, Lisa A.

Cancer Research | February 15, 2021 | Volume: 81 | Issue: 4_Supplement | Pages: PD2-10-PD2-10

10.1158/1538-7445.sabcs20-pd2-10 Get It

Abstract Background: NET is offered to postmenopausal patients (pts) with clinical stage 2/3 ER+/HER2- BC to promote breast-conserving surgery. Also limited surgical accessibility during the COVID19 pandemic has increased NET utility. Inability to identify ET-resistant disease at diagnosis risks disease progression (PD) and delays more effective treatments. Dowsett et al. recently demonstrated that baseline levels of ER, progesterone receptor (PR), Ki67 (>15% vs ≤15%), and Ki67 (>10% vs ≤10%) 2-4 weeks (wks) after starting NET may improve appropriate patient (pt) selection for NET (PMC7280290). The ER, PR and Ki67-based prediction model divides pts with primary ER+/HER2- BC into 3 groups for appropriateness for NET: (Group 1) NET is likely to be inappropriate (Allred ER <6 or ER 6 and PgR <6), (Group 2) NET may be appropriate and a biopsy for on-treatment Ki67 analysis may be considered after 2-4 wks of NET (2A: ER 7 or 8 and PgR <6 and 2B: ER 6 or 7 and PgR ≥6) given that on-treatment Ki67 >10% has been associated with worse outcome (PMC5455353), or (Group 3) NET is appropriate (ER 8 and PgR ≥6). The ALTERNATE trial (NCT01953588) randomized postmenopausal women with clinical stage II or III, ER+ (Allred score 6-8)/HER2- BC to receive anastrozole (ANA), fulvestrant (FUL), or ANA + FUL for 6 months, unless Ki67 was >10% on wk 4 or 12 biopsy, in which case pts were triaged to receive neoadjuvant chemotherapy (NCT) or surgery. As previously reported, the ET-sensitive disease (mPEPI 0 plus pCR) rates were similar across the treatment arms and overall 22% (286 of 1,299) pts had Ki67 >10% at wk 4 or 12. The ALTERNATE trial therefore provides a large independent data set to evaluate the NET appropriateness model. Results: Among 1,299 eligible pts randomized to receive 6 months of NET, 214 were excluded due to absent HR Allred score (n=41) or absence of pre-treatment and wk 4 Ki67 determinations (n=173). The proportions of the remaining 1,085 pts in Group 1, 2 and 3 were 1% (n=10), 43% (n= 468), and 56% (n=607), respectively. On-study Ki67 >10% prompting conversion from NET to NCT/Surgery occurred in: Group 1 90% (9 of 10), Group 2 30% (141 of 468), and Group 3 17% (104 of 607) (Table 1). Among the 1,075 pts in Groups 2 and 3, 260 (24%) pts had Ki67 ≤15% at baseline (BL), among whom only 14 (5.4%) had Ki67 >10% at wk 4, compared to 231 of the 815 (28.3%) who had BL Ki67 >15% and subsequent Ki67 >10% at wk 4. 2% of pts who remained on NET due to on-treatment Ki67 <10% had PD. Response and PEPI-0 rates by group will be reported. Conclusion: ALTERNATE trial data support a model whereby levels of ER, PR and Ki67 at diagnosis can be used for the identification of postmenopausal pts with primary ER+/HER2- BC who are appropriate for NET. When baseline ER Allred scores are >6 and Ki67 ≤15%, there is a low likelihood of ET-resistant disease. When BL Ki67 is >15%, ET sensitivity is variable, and on-treatment biopsy for Ki67 may assist in triaging regarding NET appropriateness, particularly given the extremely low local PD rates seen in ALTERNATE when on-treatment Ki67 was <10%. Support: U10CA180821, U10CA180882, U24CA196171, UG1CA189856, U10CA180868 (NRG); NCI BIQSFP, BCRF, Genentech, AstraZeneca. https://acknowledgments.alliancefound.org; Clinical Trials.gov Identifier: NCT01953588 Table 1 Baseline levels of ER, PR, and Ki67 in Relation to Wk 4 Ki67 (N=1,085)BaselineWeek 4GroupNERAllred ScorePRAllred ScoreKi67Ki67 ≤10%N (%)Ki67 >10%N (%)1N=26<6≤15%0 (0%)2 (100%)9 (90)N=86<6>15%1 (12.5%)7 (87.5%)2AN=647 or 8<6≤15%61 (95.3%)3 (4.7%)90 (30.1)N=2357 or 8<6>15%148 (63%)87 (37%)2BN=466 or 7≥6≤15%42 (91.3%)4 (8.7%)51 (30.2)N=1236 or 7≥6>15%76 (61.8%)47 (38.2%)3N=1508≥6≤15%143 (95.3%)7 (4.7%)104 (17.1)N=4578≥6>15%360 (78.8%)97 (21.2%) Citation Format: Matthew J Ellis, Vera Suman, A. Marilyn Leitch, Souzan Sanati, Kiran Vij, Gary W Unzeitig, Jeremy Hoog, Mark Watson, Olwen Hahn, Joseph Guenther, Abigail Caudle, Erika Crouch, Horacio Maluf, Mitch Dowsett, Amy Tiersten, Monica Mita, Wajeeha Razaq, Tina J Hieken, Yang Wang, Travis Dockter, Jo Anne Zujewski, Anna Weiss, Clifford Hudis, Eric P Winer, Kelly Hunt, Ann H Partridge, Cynthia X Ma, Lisa A Carey. Validation of a predictive model for potential response to neoadjuvant endocrine therapy (NET) in postmenopausal women with clinical stage II or III estrogen receptor positive (ER+) and HER2 negative (HER2-) breast cancer (BC): An ALTERNATE trial analysis (Alliance A011106) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD2-10.
Abstract GS4-05: Neoadjuvant chemotherapy (NCT) response in postmenopausal women with clinical stage II or III estrogen receptor positive (ER+) and HER2 negative (HER2-) breast cancer (BC) resistant to endocrine therapy (ET) in the ALTERNATE trial (Allianc
Cynthia, X. , Leitch, A. Marilyn , Sanati, Souzan , Unzeitig, Gary, Hahn, Olwen, Guenther, Joseph M., Caudle, Abigail S. , Crouch, Erika C., Maluf, Horacio , Tiersten, Amy , Mita, Monica , Razaq, Wajeeha, Dockter, Travis , Zujewski, Jo Anne , Weiss, Anna , Hudis, Clifford A. , Suman, Vera J. , Vij, Kiran R , Hoog, Jeremy , Watson, Mark A. , Hieken, Tina J. , Wang, Yang , Hunt, Kelly K. , Winer, Eric P. , Ellis, Matthew J. , Carey, Lisa A. , Partridge, Ann H.

Cancer Research | February 15, 2021 | Volume: 81 | Issue: 4_Supplement | Pages: GS4-05-GS4-05

10.1158/1538-7445.sabcs20-gs4-05 Get It

Abstract Background: Ki67 values >10% 2-4 weeks (wks) after starting neoadjuvant ET (NET) indicates persistent cell proliferation, resistance to ET, and is associated with increased risk of recurrence. The ACOSOG Z1031 trial suggested that these tumors are also relatively chemotherapy (chemo) resistant with a low pathologic complete response (pCR) rate to NCT. The ALTERNATE trial (NCT01953588) is a randomized study of neoadjuvant anastrozole (ANA), fulvestrant (FUL), or ANA + FUL in postmenopausal patients (pt) with newly diagnosed clinical stage II or III ER+ (Allred score 6-8)/HER2- BC. Ki67 >10% at wk 4 or 12 after starting NET triggered triage to NCT of physician choice or weekly paclitaxel. Pts who refused protocol-directed therapy, were not candidates for NCT, or decided to undergo immediate surgery are being followed per protocol. Here we report the rates of pCR and residual cancer burden (RCB) following NCT for pts triaged to NCT due to Ki67 >10% at wk 4 or 12. Results: Of the 1,299 eligible pts randomized to receive ANA, FUL, or ANA + FUL, 286 (22%) had Ki67 >10% at wk 4 or 12. 168 of these 286 pts (58.7%) chose to switch to NCT, 32 went to surgery (11.2%), and 86 discontinued further protocol-directed therapy (30.1%). Among the 168 pts who underwent NCT, the presenting clinical T stages were cT2 (n=113; 67.26%), cT3 (n=47; 27.98%) and cT4 (n=8; 4.76%) and N stages were cN0 (n=82; 48.8%), cN1 (n=75; 44.6%), cN2/3 (n=9; 5.4%) and cNx (n=2; 1.2%). Central ER testing was performed on pre-treatment biopsies and confirmed ER Allred score 6-8 in 155 of 168 (92.2%) pts, with the rest being ER Allred score 4-5 (n=5; 3%), ER- (Allred score 0) (n=2; 1.2%), or not tested (n=6; 3.6%). Most (n=139; 82.7%) were ER+/PR+, while 17.3% (n=29) were ER+/PR-, and tumor grades were G1 (n=10; 6%), G2 (n=99; 58.9%), G3 (n=54; 32.1%), not reported (n=5; 3%). Baseline Ki67 levels prior to NET were >10% in 94% (n=158), ≤10% in 3% (n=5), and not done in 3% (n=5). NCT regimens administered included doxorubicin/cyclophosphamide (AC) followed by paclitaxel (T) (n=60; 35.71%); weekly paclitaxel (n=56; 33.33%), docetaxel/cyclophosphamide (TC) (n=33; 19.65%), other doxorubicin and/or taxane containing regimen (n=17; 10.12%), and cyclophosphamide/methotrexate/fluorouracil (CMF) (n=2; 1.19%). 35 (20.8%) pts did not complete planned course of NCT due to toxicity (n=27) or refusal (n=8). 154 NCT pts underwent surgery (mastectomy in 40.3%, and breast conserving surgery in 59.7%). The path ypT stages were Tis/0 (n=10; 6.5%), T1 (n=62; 40.3%), T2 (n=61; 39.6%), and T3/4 (n=21; 13.6%), and the ypN stages were N0 (n=66; 42.9%), N1 (n=57; 37%), N2/3 (n=30; 19.5%), and Nx (n=1; 0.6%). Among the 168 pts who started on NCT (intent to treat population), there were 8 pCRs (no invasive disease in the breast or lymph nodes) (4.8%; 95% CI: 2.1% to 9.2%). Residual Cancer Burden (RCB) categories include RCB 0 (n=8; 4.8%), RCB 1 (n=15; 8.9%), RCB 2 (n=82; 48.8%), RCB 3 (n=42; 25.0%), and not determined (n=21; 12.5%). Correlations of baseline pt and tumor characteristics with pathology response to NCT will also be presented. Conclusion: In pts with NET-resistant ER+/HER2- BC, salvage NCT is not likely to induce a complete or near complete response. More effective treatments are needed for this high-risk ER+/HER2- pt population. Support: U10CA180821, U10CA180882, U24CA196171, UG1CA189856, U10CA180868 (NRG); NCI BIQSFP, BCRF, Genentech, AstraZeneca. https://acknowledgments.alliancefound.org. Clinical Trials.gov Identifier: NCT01953588 Citation Format: Cynthia X Ma, Vera Suman, A. Marilyn Leitch, Souzan Sanati, Kiran Vij, Gary W Unzeitig, Jeremy Hoog, Mark Watson, Olwen Hahn, Joseph Guenther, Abigail Caudle, Erika Crouch, Horacio Maluf, Amy Tiersten, Monica Mita, Wajeeha Razaq, Tina J Hieken, Yang Wang, Travis Dockter, Jo Anne Zujewski, Anna Weiss, Kelly Hunt, Clifford Hudis, Eric P Winer, Matthew J Ellis, Lisa A Carey, Ann H Partridge. Neoadjuvant chemotherapy (NCT) response in postmenopausal women with clinical stage II or III estrogen receptor positive (ER+) and HER2 negative (HER2-) breast cancer (BC) resistant to endocrine therapy (ET) in the ALTERNATE trial (Alliance A011106) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS4-05.
Abstract GS3-09: Chances of pregnancy after breast cancer, reproductive and disease outcomes: A systematic review and meta-analysis
Poorvu, Philip D. , Kim, Hee Jeong , Pistilli, Barbara , Ruddy, Kathryn J. , Sertoli, Chiara, Azim, Hatem A. , Pagani, Olivia , Blondeaux, Eva , Perachino, Marta , Bruzzone, Marco , Anderson, Richard A. , Azambuja, Evandro de , Villarreal‐Garza, Cynthia , Vaz-Luís, Inês , Saura, Cristina , Franzoi, Maria Alice , Ceppi, Marcello , Amant, Frédéric , Demeestere, Isabelle , Mastro, Lucia Del , Partridge, Ann H. , Peccatori, Fedro A , Lambertini, Matteo

Cancer Research | February 15, 2021 | Volume: 81 | Issue: 4_Supplement | Pages: GS3-09-GS3-09

10.1158/1538-7445.sabcs20-gs3-09 Get It

Abstract Background: Pregnancy-related issues are a priority for young breast cancer (BC) patients. Increasing evidence has shown that pregnancy after prior BC diagnosis is feasible. Nevertheless, few BC survivors conceive following anticancer treatment completion and many physicians remain concerned about the potentially detrimental effects of pregnancy after BC in terms of fetal/obstetrical outcomes and maternal prognosis. This systematic review and meta-analysis aims at providing updated and solid evidence on these important issues. Methods: A systematic literature review up to January 31, 2020 with no language restriction was conducted to identify studies including patients with a pregnancy after prior BC diagnosis. Chances of pregnancy after BC, fetal and obstetrical outcomes, disease-free survival (DFS) and overall survival (OS) were assessed. Pooled relative risks (RRs), hazard ratios (HRs) or odds ratio (ORs) with 95% confidence intervals (CI) were calculated using the random effects models. The study is registered with the PROSPERO registration number CRD42020158324. Results: Overall, 39 studies were included. Out of the 8,265,713 young women included in these studies, 8,093,401 were from the general population, 57,739 had cancers other than BC, 114,573 had BC. Among the 114,573 BC patients, 7,505 had a pregnancy after BC diagnosis and 107,068 did not. Compared to women from the general population, BC patients had 60% reduced chances of having a pregnancy following anticancer treatment completion (RR 0.40, 95% CI 0.32-0.49). Among other cancer patients, only women with prior cervical cancer had lower pregnancy rates (RR 0.33, 95% CI 0.31-0.35) than BC patients. Compared to the general population, BC survivors had significantly increased risks of low birth weight (OR 1.50, 95% CI 1.31-1.73), small for gestational age (OR 1.16, 95% CI 1.01-1.33), preterm delivery (OR 1.45, 95% CI 1.11-1.88) and caesarean section (OR 1.14, 95% CI 1.04-1.25). No significant increased risk of congenital abnormalities (OR 1.63, 95% CI 0.89-2.98) or other pregnancy or delivery complications (spontaneous or induced abortion, gestosis, antepartum or postpartum hemorrhage) was observed. Prior chemotherapy exposure or short pregnancy interval (defined as <2 or <5 years after BC diagnosis) were not associated with additional increased risk of complications. Pregnancy after BC was not associated with a negative impact on patients’ outcomes. Compared to BC patients without subsequent pregnancy, those with pregnancy after BC had better OS (HR 0.56, 95% CI 0.46-0.67) and DFS (HR 0.73, 95% CI 0.56-0.94). Similar results were observed in the studies correcting for the potential “healthy mother effect” (OS: HR 0.52, 95% CI 0.42-0.65; DFS: HR 0.74, 95% CI 0.58-0.96). No detrimental prognostic effect of pregnancy after BC was observed in patients with hormone-receptor positive disease (DFS: HR 1.10, 95% CI 0.73-1.66), while better outcomes were observed for those with hormone-receptor negative disease (DFS: HR 0.72, 95% CI 0.55-0.95). The safety of pregnancy after BC was observed irrespective of BRCA status, nodal status, previous chemotherapy exposure, pregnancy interval and pregnancy outcomes. Conclusions: This large meta-analysis provides solid evidence on the safety of pregnancy after prior BC diagnosis. The increased risk of fetal and obstetrical complications (but not of congenital abnormalities) calls for ensuring a closer monitoring of these pregnancies. The significantly reduced chances of conceiving as compared to the general population and other cancer patients should raise further awareness on the need to improve the oncofertility counseling of young BC patients wishing to complete their family planning following anticancer treatment completion. Citation Format: Eva Blondeaux, Marta Perachino, Marco Bruzzone, Richard A. Anderson, Evandro De Azambuja, Philip D. Poorvu, Hee Jeong Kim, Cynthia Villarreal-Garza, Barbara Pistilli, Ines Vaz-Luis, Cristina Saura, Kathryn J. Ruddy, Maria Alice Franzoi, Chiara Sertoli, Marcello Ceppi, Hatem A. Azim, Jr., Frederic Amant, Isabelle Demeestere, Lucia Del Mastro, Ann H. Partridge, Olivia Pagani, Fedro A. Peccatori, Matteo Lambertini. Chances of pregnancy after breast cancer, reproductive and disease outcomes: A systematic review and meta-analysis [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS3-09.
ProEx C Immunocytochemistry and High-Risk Human Papillomavirus DNA Testing in Papanicolaou Tests With Atypical Squamous Cell (ASC-US) Cytology: Correlation Study With Histologic Biopsy
Hornaman, Kelly, Cohen, Cynthia , Siddiqui, Momin T. , Nassar, Aziza

Archives of Pathology & Laboratory Medicine | February 11, 2021 | Volume: 132 | Issue: 10 | Pages: 1648-1652

10.5858/2008-132-1648-pciahh | PMID 18834224 Get It

Abstract Context. —Papanicolaou tests with atypical squamous cells of undetermined significance (ASC-US) cytology and adjunct testing for high-risk human papillomaviruses (hr-HPV) are helpful in detecting high-grade disease. Detection of disease may be further improved with molecular markers known to be overexpressed in cervical carcinoma. ProEx C detects 2 such molecular markers, minichromosome maintenance protein 2 and topoisomerase II, which are associated with abnormal cell cycle regulation. Objective. —To determine the utility of ProEx C as a marker for high-grade cervical intraepithelial neoplasia 2+ disease when compared with hr-HPV status in Papanicolaou tests with ASC-US cytology. Design. —A SurePath slide was prepared on all ASC-US cases from the residual SurePath vial pellet and stained using the ProEx C reagent prediluted with water-bath antigen retrieval, using a Dako autostainer. Nuclear staining of cytologically atypical squamous cells was considered a positive result. Adjunct testing for hr-HPV used Digene Hybrid Capture 2. Follow-up biopsy results were available for review following the Papanicolaou test. Results. —Two hundred patients with ASC-US diagnoses were part of this study. The sensitivities of ProEx C and hr-HPV testing in detecting high-grade cervical intraepithelial neoplasia 2+ disease were 98.04% and 82.35%, respectively, whereas the specificity for detecting high-grade disease was 74.50% and 73.15%, respectively. Conclusions. —ProEx C staining is a more sensitive and specific biomarker for detecting cervical disease than adjunct testing for hr-HPV status in Papanicolaou tests with ASC-US.
Cadherin 2-Related Arrhythmogenic Cardiomyopathy
Ghidoni, Alice , Elliott, Perry , Calkins, Hugh , James, Cynthia A. , Judge, Daniel P. , Murray, Brittney , Barc, Julien , Probst, Vincent , Schott, Jean‐Jacques , Song, Jiangping , Hauer, Richard N.W. , Hoorntje, Edgar T. , Tintelen, J. Peter van , Schulze‐Bahr, Eric , Hamilton, Robert M. , Mittal, Kirti, Semsarian, Christopher , Behr, Elijah R. , Ackerman, Michael J. , Basso, Cristina , Kotta, Maria‐Christina , Crotti, Lia , Crotti, Lia , Behr, Elijah Raphael , van Tintelen, J Peter , Kotta, Maria-Christina , Probst, Vincent , Barc, Julien , Jacques Schott, Jean , Hamilton, Robert , James, Cynthia A , Basso, Cristina , Syrris, Petros , Parati, Gianfranco , Gentilini, Davide , Mayosi, Bongani M. , Schwartz, Peter J. , Judge, Daniel P

Circulation: Genomic and Precision Medicine | February 10, 2021 | Volume: 14 | Issue: 2 | Pages: No page available

10.1161/circgen.120.003097 | PMID 33566628 Get It

Background: Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiac disease characterized by fibrofatty replacement of the right and left ventricle, often causing ventricular dysfunction and life-threatening arrhythmias. Variants in desmosomal genes account for up to 60% of cases. Our objective was to establish the prevalence and clinical features of ACM stemming from pathogenic variants in the nondesmosomal cadherin 2 (CDH2), a novel genetic substrate of ACM. Methods: A cohort of 500 unrelated patients with a definite diagnosis of ACM and no disease-causing variants in the main ACM genes was assembled. Genetic screening of CDH2 was performed through next-generation or Sanger sequencing. Whenever possible, cascade screening was initiated in the families of CDH2 -positive probands, and clinical evaluation was performed. Results: Genetic screening of CDH2 led to the identification of 7 rare variants: 5, identified in 6 probands, were classified as pathogenic or likely pathogenic. The previously established p.D407N pathogenic variant was detected in 2 additional probands. Probands and family members with pathogenic/likely pathogenic variants in CDH2 were clinically evaluated, and along with previously published cases, altogether contributed to the identification of gene-specific features (13 cases from this cohort and 11 previously published, for a total of 9 probands and 15 family members). Ventricular arrhythmic events occurred in most CDH2 -positive subjects (20/24, 83%), while the occurrence of heart failure was rare (2/24, 8.3%). Among probands, sustained ventricular tachycardia and sudden cardiac death occurred in 5/9 (56%). Conclusions: In this worldwide cohort of previously genotype-negative ACM patients, the prevalence of probands with CDH2 pathogenic/likely pathogenic variants was 1.2% (6/500). Our data show that this cohort of CDH2 -ACM patients has a high incidence of ventricular arrhythmias, while evolution toward heart failure is rare.
Predictors of Survival and Time to Progression to Myeloid Neoplasm in Patients with Clonal Cytopenias
Nanaa, Ahmad , Nana, Rama, Nguyen, Phuong L., Hengel, Cynthia, Geyer, Susan M. , He, Rong , Viswanatha, David S., Timm, Michael, Salama, Mohamed E. , Litzow, Mark R. , Patnaik, Mrinal M. , Al‐Kali, Aref , Xie, Zhuoer , Jevremović, Dragan , Shi, Min , Greipp, Patricia T. , Alkhateeb, Hassan B. , Hogan, William J. , Shah, Meera

Blood | February 8, 2021 | Volume: 136 | Issue: Supplement 1 | Pages: 26-27

10.1182/blood-2020-142181 Get It

Background: Clonal cytopenias of Undetermined Significance (CCUS) have a higher risk of progression to myeloid neoplasm (MN) compared to idiopathic cytopenias of undetermined significance (ICUS) (Malcovati et al., Blood, 2017). The implementation of flow cytometric (FC) immune-phenotyping and next generation sequencing (NGS) in clinical practice has improved the diagnosis of these entities but the clinical significance and interaction of these abnormal results are still unknown. In this study we investigated predictive factors that play role in survival and progression to MN in patients with ICUS/CCUS. Methods: Patients (Pts) who had undergone evaluation for unexplained cytopenia and had undergone FC and bone marrow morphological assessment between 3/2015-3/2020 at Mayo Clinic Rochester were included. Pts were excluded if a malignant hematological disorder was diagnosed prior to the time of FC. FC included evaluation of the following parameters: Abnormal expression of HLA-DR/CD13, CD2, CD7, CD45, and CD56 on blasts; and abnormal CD13/CD16 expression and side scatter on granulocytic cells. NGS panel up to 2018 included 34 genes, ASXL1, BCOR, BRAF, CALR, CBL, CEBPA, CSF3R, DNMT3A, ETV6, EZH2, FLT3, GATA1, GATA2, IDH1, IDH2, JAK2, KIT, KRAS, MPL, MYD88, NOTCH1, NPM1, NRAS, PHF6, PTPN11, RUNX1, SETBP1, SF3B1, TERT, TET2, TP53, U2AF1, WT1, and ZRSR2; in 2018, BRAF was omitted and 12 genes were added, ANRD26, DDX41, ELANE, ETNK1, KDM6A, MYD88, NOTCH1, RAD21, SH2B3, SRP72, SMC3, and STAG2. Results: Characteristics: Of 490 consecutive pts, 238 (median age 69 years (range 19-92), 66% males) met our inclusion criteria as ICUS. 86 (36%) pts had CCUS (abnormal cytogenetics and/or tested positive for pathogenic mutations on NGS). After a median follow-up of 28 months (95% CI: 20 to 31 months), 21 (25%) patients developed MN and 23 (27%) died during follow-up. Comparing ICUS vs CCUS: upon comparing CCUS pts to ICUS, several factors were found to be significantly different: CCUS pts were older (p= .02); majority male (p= .04), had more abnormal HLA-DR/CD13 (p <.0001), more side-scattered light by FC (p <.0001), more pancytopenia on follow up (p= .02) and more morphologic atypia (<.0001). Overall survival (OS) outcomes in CCUS: Several covariates were significant in univariate models, and model selection was used to generate a risk score based on abnormal CD7, abnormal CD13/CD16, abnormal HLA-DR/CD13, splenomegaly and history of prior chemotherapy or radiotherapy (range: 0 - 4; HR=2.58, [95 CI: 1.69 - 3.94], p<.0001). Risk scores were grouped as low risk (score=0), intermediate risk (score=1), and high risk (score=2+), with estimated 2-yr-OS of 95%, 84%, 40%, respectively (Figure 1). An extended risk score model including NGS factors added ASXL1 and IDH1 mutation status to the previous model (range: 0 - 6; HR=2.72, [95 CI 1.82 - 4.06], p<0.0001). MN-free survival (MNFS) in CCUS: 37 pts either progressed to MN and/or died with a median follow up time for MNFS of 22.4 months. Similar for OS, model selection approaches yielded a composite risk score: splenomegaly, BCOR mutation status, mutation in RAS signaling pathway, abnormal expression of flow markers CD13/CD16, HLA-DR/CD13 or CD7 (HR=3.23, [95 CI: 1.90 - 5.49], p=<0.0001). Risk scores were grouped as low risk (score=0), intermediate risk (score=1), and high risk (score ≥ 2), with estimated 1-yr MNFS of 84%, 74%, and 31%, respectively (Figure 2). Conclusion: CCUS has unique features compared to ICUS. Several factors, including clinical characteristics, immune-phenotyping by FC, and somatic mutations have important impact on risk of progression to MN and on overall survival. Our findings serve as proof-of-concept that such integrated models could help identify CCUS patients at higher risks for progression to MN or death. They can guide treatment accordingly and should be evaluated further. Disclosures Shah: Dren Bio: Consultancy.
Patient-reported sexual function of breast cancer survivors with genitourinary syndrome of menopause after fractional CO2 laser therapy
Zvinovski, Filadelfiya , Hudson, Catherine O., Hundley, Andrew F., Evans, Cynthia, Stephens, Julie , Arthur, Elizabeth , Ramaswamy, Bhuvaneswari , Reinbolt, Raquel E. , VanDeusen, Jeffrey , Williams, Nicole , Sardesai, Sagar , Loprinzi, Charles L. , Lustberg, Maryam B. , Lustberg, Maryam , Quick, Allison , Noonan, Anne M. , Wesolowski, Robert , Stover, Daniel G. , Faubion, Stephanie S.

Menopause | February 6, 2021 | Volume: 28 | Issue: 6 | Pages: 642-649

10.1097/gme.0000000000001738 | PMID 33534429 Get It

Abstract Objective: The objective of this pilot study was to evaluate the change in sexual function following treatment with fractional CO2 laser therapy in breast cancer (BC) survivors with genitourinary syndrome of menopause (GSM). Methods: A single-arm feasibility study of BC survivors with symptoms of GSM, including dyspareunia and/or vaginal dryness, was conducted. Participants who received three treatments with fractional CO2 laser and 4-week follow-up were contacted for patient-reported outcomes and adverse events at 12 months. Sexual function was measured using the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale Revised (FSDS-R). Descriptive statistics were calculated for patient demographics and disease characteristics for the set of participants who agreed to long-term follow-up and those who were lost to follow-up. FSFI and FSDS-R scores were summarized at baseline, 4 weeks and 12 months, as well as the change from baseline, and were compared using a Wilcoxon signed rank test. Results: A total of 67 BC survivors enrolled, 59 completed treatments and 4-week follow-up; 39 participated in the 12 month follow-up. The overall FSFI score improved from baseline to 4-week follow-up (median Δ 8.8 [Q1, Q3] (QS) (2.2, 16.7)], P < 0.001). There were improvements at 4 weeks in all domains of the FSFI (P < 0.001 for each) including desire (median Δ 1.2; QS [0.6, 1.8]), arousal (median Δ 1.2; QS [0.3, 2.7]), lubrication (median Δ 1.8 (0, 3.3), orgasm (median Δ 1.2; QS [0, 3.6]), satisfaction (median Δ 1.6 (0.4, 3.2)), and pain (median Δ 1.6 (0, 3.6). The FSDS-R score also improved from baseline to 4-week follow-up (median Δ −10.0; QS [−16, −5] P < 0.001) indicating less sexually related distress. The scores of the FSFI and FSDS-R remained improved at 12 months and there were no serious adverse events reported. Conclusions: In BC survivors with GSM, the total and individual domain scores of the FSFI and the FSDS-R improved after fractional CO2 laser therapy. Video Summary: http://links.lww.com/MENO/A711.
Eosinophils attenuate hepatic ischemia-reperfusion injury in mice through ST2-dependent IL-13 production
Wang, Yaochun , Yang, Yang , Wang, Meng , Wang, Shuhong , Jeong, Jong‐Min , Xu, Long , Wen, Yankai , Emontzpohl, Christoph , Atkins, Constance L. , Duong, Kevin , Moreno, Nicolas F. , Yuan, Xiaoyi , Hall, David R. , Dar, Wasim , Feng, Dechun , Bynon, John S. , Akira, Shizuo , Brown, Jared M. , Jacobsen, Elizabeth A. , Ju, Cynthia, Atkins, Constance Lynn , Xu, Yong , Czigany, Zoltan , Colgan, Sean P , Bynon, J Steve , Jacobsen, Elizabeth A , Ju, Cynthia , Wen, Yankai , Moreno, Nicolas F , Yang, Yang , Gao, Bin , Eltzschig, Holger K.

Science Translational Medicine | February 3, 2021 | Volume: 13 | Issue: 579 | Pages: No page available

10.1126/scitranslmed.abb6576 | PMID 33536281 Get It

Eosinophils protect against liver injury during orthotopic liver transplantation and other conditions of hepatic ischemia-reperfusion injury in mice.
The feasibility of low iodine dynamic CT angiography with test bolus for evaluation of lower extremity peripheral artery disease
Inoue, Akitoshi , Vrtiska, Terri J., Lee, Yong S. , Vasconcelos, Rogerio N., Weber, Nikkole M. , Halaweish, Ahmed F., Duba, Irene , Williamson, Eric E. , Fletcher, Joel G , Inoue, Akitoshi , Leng, Shuai , McCollough, Cynthia H. , Fletcher, Joel G.

Vascular | January 18, 2021 | Volume: 29 | Issue: 6 | Pages: 927-937

10.1177/1708538120986304 | PMID 33459205 Get It

Objective This study aims to determine if low iodine dynamic computed tomography angiography performed after a fixed delay or test bolus acquisition demonstrates high concordance with clinical computed tomography angiography (using a routine amount of iodinated contrast) to display lower extremity peripheral arterial disease. Methods After informed consent, low iodine dynamic computed tomography angiography examination (using either a fixed delay or test bolus) using 50 ml of iodine contrast media was performed. A subsequent clinical computed tomography angiography using standard iodine dose (115 or 145 ml) served as the reference standard. A vascular radiologist reviewed dynamic and clinical computed tomography angiography images to categorize the lumen into “not opacified”, “<50% stenosis”, “ 50 ̶70% stenosis”, “>70% stenosis”, and “occluded” for seven arterial segments in each lower extremity. Concordance between low iodine dynamic computed tomography angiography and the routine iodine reference standard was calculated. The clinical utility of 4D volume-rendered images was also evaluated. Results Sixty-eight patients (average age 66.1 ± 12.3 years, male; female = 49: 19) were enrolled, with 34 patients each undergoing low iodine dynamic computed tomography angiography using fixed delay and test bolus techniques, respectively. One patient assigned to the test bolus group did not undergo low iodine computed tomography angiography due to unavailable delayed time. The fixed delay was 13 s, with test bolus acquisition resulting in a mean variable delay prior to image acquisition of 19.5 s (range; 8–32 s). Run-off to the ankle was observed using low iodine dynamic computed tomography angiography following fixed delay and test bolus acquisition in 76.4% (26/34) and 100% (33/33) of patients, respectively ( p = 0.005). Considering extremities with run-off to the ankle and without severe artifact, the concordance rate between low iodine dynamic computed tomography angiography and the routine iodine reference standard was 86.8% (310/357) using fixed delay and 97.9% (425/434) using test bolus ( p < 0.001). 4D volume-rendered images using fixed delay and test bolus demonstrated asymmetric flow in 57.7% (15/26) and 58.1% (18/31) ( p = 0.978) of patients, and collateral blood flow in 11.5% (3/26) and 22.6% (7/31) of patients ( p = 0.319), respectively. Conclusion Low iodine dynamic computed tomography angiography with test bolus acquisition has a high concordance with routine peripheral computed tomography angiography performed with standard iodine dose, resulting in improved run-off to the ankle compared to dynamic computed tomography angiography performed after a fixed delay. This method is useful for minimizing iodine dose in patients at risk for contrast-induced nephropathy. 4D volume-rendered computed tomography angiography images provide useful dynamic information.