Publications by authors named "Anita Aggarwal"

43 Publications

Gender Disparity in Breast Cancer: A Veteran Population-Based Comparison.

Clin Breast Cancer 2021 Jan 26. Epub 2021 Jan 26.

Veterans Affairs Medical Center, 50 Irving Street NW, Washington DC.

Background: Male breast cancer (MBC) comprises <1% of all cancers and continues to rise. Because of rarity, there is paucity in the literature; therefore, management of MBC is generalized from female breast cancer (FBC).

Methods: Data from 152 VA Medical Centers were used to analyze the database of Veteran patient with breast cancer diagnosed between 1998 and 2016 using biostatistical software (SAS 9.3). Our primary objective is to compare patient's demographics, breast cancer characteristics, and outcomes for male and female Veterans.

Finding: In total, 8864 patients' records were reviewed;1528 MBC were compared with 7336 FBC with a mean follow up time of 5.5 years (SD 4.17). The mean age at diagnosis was 68.6 years and 57.3 years for MBC and FBC, respectively (P < .0001). Higher numbers of MBC patients (95%) were >50 years of age compared to FBC patients (72%). More MBC patients (16.8 vs. 9.1% and 9 vs. 4%) presented with higher disease stage (III and IV, respectively). Estrogen receptor-positive tumors were more common in MBC (59 versus 52%). Hormonal treatment was received by 27% of MBC versus 19% FBC; chemotherapy 21.3% versus 41.5% and radiation 23.5% versus 60.9%. Forty-two percent MBC and 20% FBC Veterans died during study. Male patients had higher death rate 1.285 (95% CI: 1.150, 1.434, P < .0001) compared to females after adjusting data for age, race, stage, and grade.

Interpretation: To the best of our knowledge, this is the largest comparison series of MBC and FBC to date in the Veterans population. The higher mortality rate in MBC patients may be due to late presentation, higher stage at the time of diagnosis and/or tumor biology. Veteran's exposures to hazardous materials during their military deployments as an additional factor for worse prognosis need further investigation.
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http://dx.doi.org/10.1016/j.clbc.2021.01.013DOI Listing
January 2021

A Case Report of Small Lymphocytic Lymphoma Mimicking Primary Cutaneous Marginal Zone Lymphoma With Plasmacytic Differentiation.

Am J Dermatopathol 2021 Feb 16. Epub 2021 Feb 16.

Department of Pathology, The George Washington University, Washington, DC; Department of Medicine, Hematology/Oncology, Veterans Affairs Medical Center, Washington, DC; Department of Medicine, The George Washington University, Washington, DC; and Department of Pathology, Veterans Affairs Medical Center, Washington, DC.

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http://dx.doi.org/10.1097/DAD.0000000000001928DOI Listing
February 2021

Retraction Note: Engineered Polyallylamine Nanoparticles for Efficient In Vitro Transfection.

Pharm Res 2020 Dec 3;37(12):253. Epub 2020 Dec 3.

Institute of Genomics and Integrative Biology, Delhi University Campus, Mall Road, Delhi, 110007, India.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1007/s11095-020-02971-0.
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http://dx.doi.org/10.1007/s11095-020-02971-0DOI Listing
December 2020

High Viral Load and Poor Ventilation: Cause of High Mortality From COVID-19.

Asia Pac J Public Health 2020 Sep-Oct;32(6-7):377-378. Epub 2020 Jul 25.

Sir Ganga Ram Hospital, New Delhi, India.

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http://dx.doi.org/10.1177/1010539520944725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521001PMC
July 2020

ABO Blood Group as a Prognostic Factor in Patients with Diffuse Large B Cell Lymphoma.

Clin Lymphoma Myeloma Leuk 2020 08 16;20(8):561-562. Epub 2020 Mar 16.

Department of Pathology, George Washington University, Washington, DC; Department of Pathology, Veterans Health Administration, Washington, DC.

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http://dx.doi.org/10.1016/j.clml.2020.03.001DOI Listing
August 2020

Breast Cancer Risk Assessment and Chemoprevention Use Among Veterans Affairs Primary Care Providers: A National Online Survey.

Mil Med 2020 03;185(3-4):512-518

Huntsman Cancer Institute 1950, 2000 Cir of Hope Dr, Salt Lake City, UT 84112, George E Wahlen VA 500 Foothill Dr Salt Lake City, UT 84148.

Introduction: Breast cancer is the most common cancer diagnosed among women and the second most common cause of cancer death among women. There are ways to reduce a woman's risk of breast cancer; however, most eligible women in the United States are neither offered personalized screening nor chemoprevention. Surveys have found that primary care providers are largely unaware of breast cancer risk assessment models or chemoprevention. This survey aims to investigate Veterans Health Administration primary care providers' comfort level, practice patterns, and knowledge of breast cancer risk assessment and chemoprevention.

Materials And Methods: An online, Research Electronic Data Capture-generated survey was distributed to VHA providers in internal medicine, family medicine, and obstetrics/gynecology. Survey domains were provider demographics, women's health experience, comfort level, practice patterns, barriers to using risk models and chemoprevention, and knowledge of chemoprevention.

Results: Of the 167 respondents, 33.1% used the Gail model monthly or more often and only 2.4% prescribed chemoprevention in the past 2 years. Most VHA primary care providers did not answer chemoprevention knowledge questions correctly. Designated women's health providers were more comfortable with risk assessment (P < 0.018) and chemoprevention (P < 0.011) and used both breast cancer risk models (P < 0.0045) and chemoprevention more often (P < 0.153). Reported barriers to chemoprevention were lack of education and provider time.

Conclusions: VHA providers and women Veterans would benefit from a system to ensure that women at increased risk of breast cancer are identified with risk modeling and that risk reduction options, such as chemoprevention, are offered when appropriate. VHA providers requested risk reduction education, which could improve primary care provider comfort level with chemoprevention.
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http://dx.doi.org/10.1093/milmed/usz291DOI Listing
March 2020

Chronic Myeloid Leukemia as Secondary Malignancy Following the Treatment of Hodgkin Lymphoma: A Case Series.

Anticancer Res 2019 Aug;39(8):4333-4335

The George Washington University School of Medicine, Washington, DC, U.S.A.

Secondary malignancies are relatively common and clinically important phenomena following both chemotherapy and radiotherapy. The majority of these cases are acute leukemias, the occurrence of which have been thoroughly documented and studied. More rarely, chronic myeloid leukemias (CML) may arise subsequent to treatment of a primary malignancy. Literature review on such developments following treatment of Hodgkin's Lymphoma (HL) is scant. Herein, the authors present three cases of CML diagnosed within five years of treatment initiation for Hodgkin's Lymphoma (HL); one of the three patients had CML with atypical variant carrying a rare mutation with BCR-JAK2 fusion.
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http://dx.doi.org/10.21873/anticanres.13600DOI Listing
August 2019

Treatment and Long-Term Clinical Outcomes of Incidental Pulmonary Embolism in Patients With Cancer: An International Prospective Cohort Study.

J Clin Oncol 2019 07 22;37(20):1713-1720. Epub 2019 May 22.

25 University G D'Annunzio, Chieti-Pescara, Italy.

Purpose: Pulmonary embolism is incidentally diagnosed in up to 5% of patients with cancer on routine imaging scans. The clinical relevance and optimal therapy for incidental pulmonary embolism, particularly distal clots, is unclear. The aim of the current study was to assess current treatment strategies and the long-term clinical outcomes of incidentally detected pulmonary embolism in patients with cancer.

Patients And Methods: We conducted an international, prospective, observational cohort study between October 22, 2012, and December 31, 2017. Unselected adults with active cancer and a recent diagnosis of incidental pulmonary embolism were eligible. Outcomes were recurrent venous thromboembolism, major bleeding, and all-cause mortality during 12 months of follow-up. Outcome events were centrally adjudicated.

Results: A total of 695 patients were included. Mean age was 66 years and 58% of patients were male. Most frequent cancer types were colorectal (21%) and lung cancer (15%). Anticoagulant therapy was initiated in 675 patients (97%), of whom 600 (89%) were treated with low-molecular-weight heparin. Recurrent venous thromboembolism occurred in 41 patients (12-month cumulative incidence, 6.0%; 95% CI, 4.4% to 8.1%), major bleeding in 39 patients (12-month cumulative incidence, 5.7%; 95% CI, 4.1% to 7.7%), and 283 patients died (12-month cumulative incidence, 43%; 95% CI, 39% to 46%). The 12-month incidence of recurrent venous thromboembolism was 6.4% in those with subsegmental pulmonary embolism compared with 6.0% in those with more proximal pulmonary embolism (subdistribution hazard ratio, 1.1; 95% CI, 0.37 to 2.9; = .93).

Conclusion: In patients with cancer with incidental pulmonary embolism, risk of recurrent venous thromboembolism is significant despite anticoagulant treatment. Patients with subsegmental pulmonary embolism seemed to have a risk of recurrent venous thromboembolism comparable to that of patients with more proximal clots.
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http://dx.doi.org/10.1200/JCO.18.01977DOI Listing
July 2019

Natural history of benign ethnic neutropenia in individuals of African ancestry.

Blood Cells Mol Dis 2019 07 15;77:12-16. Epub 2019 Mar 15.

Molecular and Clinical Hematology Branch, NHLBI, NIH, United States of America. Electronic address:

Background: Benign ethnic neutropenia (BEN), defined by neutrophil count <1.5 k/μL in the absence of other causes, is an asymptomatic condition more commonly observed in individuals of African ancestry. However, the natural history of this condition has been less well described.

Methods: Individuals with BEN were retrospectively identified by chart review or referral to hematology clinics. They were then invited to enroll in a prospective natural history study. Retrospective and prospective clinical and laboratory data were combined for descriptive analyses.

Findings: 46 participants, younger and older adults from 2 institutions, had BEN. Hypertension was reported in 30%, musculoskeletal disorders in 15%, and upper respiratory infection in 33% of these adults. Their leukopenia resulted from isolated neutropenia, ranging from 1000 and 1500 cells/μL. The severity of infections was mild and the frequency was similar to other healthy individuals in the ambulatory clinic.

Interpretation: In this group of BEN participants, their leukopenia was stable over time, and they had low rates of infections or common medical disorders, confirming the benign nature of this condition. The presence of BEN in children, younger adults, and older adults suggest a hereditary pattern for BEN.
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http://dx.doi.org/10.1016/j.bcmd.2019.01.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541485PMC
July 2019

Retraction notice to "Imidazolyl-PEI modified nanoparticles for enhanced gene delivery" [International Journal of Pharmaceutics 335 (2007) 180-192].

Int J Pharm 2019 04;560:416

Institute of Genomics and Integrative Biology, Mall Road, Delhi University Campus, Delhi 110007, India.

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http://dx.doi.org/10.1016/j.ijpharm.2019.03.023DOI Listing
April 2019

Why Am I Being Treated Like a Female Breast Cancer Patient?

Fed Pract 2018 Feb;35(Suppl 1):S20-S21

is a Past President, AVAHO (2016), Hematologist/Oncologist at Washington DC VAMC and Associate Professor of Hematology/Oncology at Georgetown University School of Medicine in Washington DC. is a male breast cancer advocate and is pursuing a MS in psychology.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375517PMC
February 2018

Targeting protein disulfide isomerase with the flavonoid isoquercetin to improve hypercoagulability in advanced cancer.

JCI Insight 2019 02 21;4(4). Epub 2019 Feb 21.

Division of Hemostasis and Thrombosis and.

Background: Protein disulfide isomerase (PDI) is a thiol isomerase secreted by vascular cells that is required for thrombus formation. Quercetin flavonoids inhibit PDI activity and block platelet accumulation and fibrin generation at the site of a vascular injury in mouse models, but the clinical effect of targeting extracellular PDI in humans has not been studied.

Methods: We conducted a multicenter phase II trial of sequential dosing cohorts to evaluate the efficacy of targeting PDI with isoquercetin to reduce hypercoagulability in cancer patients at high risk for thrombosis. Patients received isoquercetin at 500 mg (cohort A, n = 28) or 1000 mg (cohort B, n = 29) daily for 56 days, with laboratory assays performed at baseline and the end of the study, along with bilateral lower extremity compression ultrasound. The primary efficacy endpoint was a reduction in D-dimer, and the primary clinical endpoint included pulmonary embolism or proximal deep vein thrombosis.

Results: The administration of 1000 mg isoquercetin decreased D-dimer plasma concentrations by a median of -21.9% (P = 0.0002). There were no primary VTE events or major hemorrhages observed in either cohort. Isoquercetin increased PDI inhibitory activity in plasma (37.0% in cohort A, n = 25, P < 0.001; 73.3% in cohort B, n = 22, P < 0.001, respectively). Corroborating the antithrombotic efficacy, we also observed a significant decrease in platelet-dependent thrombin generation (cohort A median decrease -31.1%, P = 0.007; cohort B median decrease -57.2%, P = 0.004) and circulating soluble P selectin at the 1000 mg isoquercetin dose (median decrease -57.9%, P < 0.0001).

Conclusions: Isoquercetin targets extracellular PDI and improves markers of coagulation in advanced cancer patients.

Trial Registration: Clinicaltrials.gov NCT02195232.

Funding: Quercegen Pharmaceuticals; National Heart, Lung, and Blood Institute (NHLBI; U54HL112302, R35HL135775, and T32HL007917); and NHLBI Consortium Linking Oncology and Thrombosis (U01HL143365).
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http://dx.doi.org/10.1172/jci.insight.125851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478409PMC
February 2019

Human Case of Streptococcus suis Disease, Ontario, Canada.

Emerg Infect Dis 2017 12;23(12):2107-2109

We report a case of Streptococcus suis human disease in Ontario, Canada, caused by a serotype 2 strain genotypically similar to those commonly isolated from pigs in North America. Initially, the isolate was misidentified as a viridans group Streptococcus. Human S. suis infections may be underdiagnosed in North America.
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http://dx.doi.org/10.3201/eid2312.171005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5708224PMC
December 2017

DA-EPOCH-R for post-transplant lymphoproliferative disorders.

Eur J Haematol 2017 Sep 13;99(3):283-285. Epub 2017 Jul 13.

Department of Hematology, MedStar Washington Cancer Institute, Washington, DC, USA.

Background: Post-transplant lymphoproliferative disorders (PTLD) are a potentially fatal group of neoplasms arising in an immunodeficient environment. Although the cornerstone of treatment is reduced immunosuppression (RI), advanced cases often warrant treatment with chemoimmunotherapy. The chemoimmunotherapy regimen of dose-adjusted (DA)-EPOCH-R is superior to R-CHOP in HIV associated aggressive lymphomas, suggesting that it might also be favorable in the setting of PTLD.

Methods: We performed a retrospective analysis of patients with advanced monomorphic PTLD treated with first line DA-EPOCH-R in addition to RI at our institution from 2003-2016.

Results: Seven patients were included. Mean age was 51 and mean time from transplant to diagnosis was 71 months. Six of the seven patients received a kidney transplant, six had stage III or IV disease, six had tumors that were EBV positive, and six completed therapy. All six patients who completed therapy achieved a complete response. Mean PFS and OS were 46.6 and 52.6 months, respectively. Treatment was well-tolerated with no significant treatment related morbidity or mortality.

Conclusions: Our findings support several observations in the literature that DA-EPOCH-R is efficacious and well-tolerated for the treatment of advanced, monomorphic PTLD.
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http://dx.doi.org/10.1111/ejh.12904DOI Listing
September 2017

Cancer Care Collaborative Approach to Optimize Clinical Care.

Fed Pract 2017 May;34(Suppl 3):S42-S49

is an associate director and is an industrial engineer for clinical partnerships for healthcare transformation at the VA-Center for Applied Systems Engineering at the Detroit VAMC in Michigan. is the VHA national program manager for Prevention Policy for the National Center for Health Promotion and Disease Prevention, and is the VHA national program director for oncology and patient care services chief of hematology and oncology, both at Durham VAMC in North Carolina. is a hemotology and medical oncology physician at the Washington DC VAMC, and Ms. Hoffman-Hōgg also is the VHA national oncology clinical advisor for the Office of Nursing Services, both in Washington, DC. is the specialty chief of hematology and oncology, and is research coordinator for the Bronx Veterans Medical Research Foundation, both at James J. Peters VAMC in Bronx, New York.

A collaboration between clinicians and industrial engineers resulted in significant improvements in cancer screening, the development of toolkits, and more efficient care for hepatocellular carcinoma and breast, colorectal, lung, head and neck, and prostate cancers.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375583PMC
May 2017

Best Practices in Hematology and Oncology Care.

Fed Pract 2016 Feb;33(Suppl 1):13S-14S

Washington DC VA Medical Center, AVAHO Immediate Past President.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375408PMC
February 2016

TMSB4Y is a candidate tumor suppressor on the Y chromosome and is deleted in male breast cancer.

Oncotarget 2015 Dec;6(42):44927-40

The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Male breast cancer comprises less than 1% of breast cancer diagnoses. Although estrogen exposure has been causally linked to the development of female breast cancers, the etiology of male breast cancer is unclear. Here, we show via fluorescence in situ hybridization (FISH) and droplet digital PCR (ddPCR) that the Y chromosome was clonally lost at a frequency of ~16% (5/31) in two independent cohorts of male breast cancer patients. We also show somatic loss of the Y chromosome gene TMSB4Y in a male breast tumor, confirming prior reports of loss at this locus in male breast cancers. To further understand the function of TMSB4Y, we created inducible cell lines of TMSB4Y in the female human breast epithelial cell line MCF-10A. Expression of TMSB4Y resulted in aberrant cellular morphology and reduced cell proliferation, with a corresponding reduction in the fraction of metaphase cells. We further show that TMSB4Y interacts directly with β-actin, the main component of the actin cytoskeleton and a cell cycle modulator. Taken together, our results suggest that clonal loss of the Y chromosome may contribute to male breast carcinogenesis, and that the TMSB4Y gene has tumor suppressor properties.
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http://dx.doi.org/10.18632/oncotarget.6743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792601PMC
December 2015

Deep vein thrombosis (DVT) and pulmonary embolism (PE): awareness and prophylaxis practices reported by patients with cancer.

Cancer Invest 2015 16;33(9):405-10. Epub 2015 Jul 16.

a 1 George Washington University and Veterans Affairs Medical Center , Washington, DC.

Patients with cancer are at increased risk for venous thromboembolism (VTE). An online survey to measure PE/DVT terminology awareness and understanding of VTE risks revealed 24% and 15% of the 500 cancer patients surveyed had heard of term DVT/PE; 19% and 17% could name signs/ symptoms of DVT/PE; 3% recognized cancer treatments as risk factors for DVT/PE. Only 25% of the patients received prevention education from providers; <50% received VTE prophylaxis. Cancer patient awareness of VTE terminology and cancer and/or its treatment as risk for VTE is low. More effective patient/physician dialogue about VTE risk and thromboprophylaxis is needed.
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http://dx.doi.org/10.3109/07357907.2015.1048871DOI Listing
February 2016

New Treatments for Chronic Lymphocytic Leukemia.

Authors:
Anita Aggarwal

Fed Pract 2015 May;32(Suppl 4):54S-55S

is a hematologist/oncologist at the Washington DC VAMC and associate professor at George Washington University and Georgetown University, both in Washington, DC. Dr. Aggarwal is also president elect of the Association of VA Hematology/Oncology.

The treatment of chronic lymphocytic leukemia has undergone a dramatic transformation since the FDA approved new, targeted agents, but patients and doctors must also consider cost and toxicity.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375454PMC
May 2015

Advances in Targeted Therapy for Breast Cancer.

Fed Pract 2015 May;32(Suppl 4):46S-49S

is a fellow in hematology/oncology and is an associate professor of medicine, both at The George Washington University in Washington, DC. Dr. Aggarwal is also an associate professor of medicine at Georgetown University and a hematologist/oncologist at the Washington DC VAMC, both in Washington, DC. She is also president elect of Association of VA Hematology and Oncology..

Recent clinical trials have provided additional first-line therapeutic treatment options that improve overall survival and progression-free survival in women with breast cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375455PMC
May 2015

Breast cancer in male veteran population: an analysis from VA cancer registry.

J Community Support Oncol 2014 Aug;12(8):293-7

Department of Oncology/Hematology, Veterans Afairs Medical Center, Washington DC USA Email:

Background: Male breast cancer is rare and makes up < 1% of all cases of breast cancers. Treatment and survival stage per stage is mainly based on what is known from female breast cancer.

Objectives: We determined the pathological features, stage, treatment of breast cancer in male veterans and their survival outcome.

Methods: Medical records of male patients diagnosed with breast cancer at the Veterans Affairs Medical Centers of Washington DC, Baltimore, Maryland, and Martinsburg, West Virginia, from 1992-2012 were reviewed after iInstitutional review board approval.

Results: From 1995-2012, 51 male patients with breast cancer were identifed from cancer registry. Of those, 57% were African American, 41% white, and 2% other race. Median age was 68 years (range, 44-86 years). Palpable mass was presenting symptoms in 80%, and gynecomastia or bloody nipple discharge in 16%. Family history of breast cancer in immediate family was positive in 11 patients without mention of BRCA genes except in one who was BRCA2-positve. ER/PR (estrogen-/progesterone-receptor) was positive in 71%, ER-positive/PR-negative in 2%, ER-positive/PR-positive /HER2-positive in 4%, ER-negative/PR-negative /HER2-triple negative in 4%. In all, 41% and 57% had right and left breast cancer, respectively; 80% had mastectomy, 36% had lymph node involvement (1-13 LN), 90% had invasive ductal carcinoma, 8% DCIS, and 2% sarcoma. Cancer in 26% was stage I, 38% stage II, 18% stage III and 8% stage IV. Twenty four percent of the patients had combination chemotherapy, and 66% were given tamoxifen. Eight percent had relapsed or recurrent disease within 1-5 years of their diagnosis and died within 2-12 years after the relapse. At median follow-up of 174 months (range, 4 months-19 years), 56% had died, 42% were alive, and 6% had been lost to follow-up.

Limitations: This is a very small retrospective chart review. Further large prospective studies are desired.

Conclusions: Median age at diagnosis of breast cancer seems to be higher in men (70 years) than it is in women (60 years). Invasive ductal carcinoma is the main pathology, and 73% of the tumors were ER-positive. The survival rate at more than 10 years of follow-up was about 40%. Stage versus survival revealed no difference in mortality.
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http://dx.doi.org/10.12788/jcso.0066DOI Listing
August 2014

Pattern of frequent but nontargeted pharmacologic thromboprophylaxis for hospitalized patients with cancer at academic medical centers: a prospective, cross-sectional, multicenter study.

J Clin Oncol 2014 Jun 5;32(17):1792-6. Epub 2014 May 5.

Jeffrey I. Zwicker, Adam Rojan, and Renee Funches, Beth Israel Deaconess Medical Center and Harvard Medical School; Federico Campigotto and Donna Neuberg, Dana-Farber Cancer Institute, Boston, MA; Nadia Rehman and Ted Wun, University of California at Davis School of Medicine; Nadia Rehman and Ted Wun, VA Northern California Health Care System, Sacramento, CA; Gregory Connolly, University of Rochester Medical Center, Rochester, NY; Jonathan Webster and Michael B. Streiff, Johns Hopkins University School of Medicine, Baltimore, MD; Anita Aggarwal, Dalia Mobarek, Charles Faselis, and Frederick R. Rickles, Veterans Administration Medical Center and The George Washington University, Washington, DC; and Alok A. Khorana, Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH.

Purpose: Hospitalized patients with cancer are considered to be at high risk for venous thromboembolism (VTE). Despite strong recommendations in numerous clinical practice guidelines, retrospective studies have shown that pharmacologic thromboprophylaxis is underutilized in hospitalized patients with cancer.

Patients And Methods: We conducted a prospective, cross-sectional study of hospitalized patients with cancer at five academic hospitals to determine prescription rates of thromboprophylaxis and factors influencing its use during hospitalization.

Results: A total of 775 patients with cancer were enrolled across five academic medical centers. Two hundred forty-seven patients (31.9%) had relative contraindications to pharmacologic prophylaxis. Accounting for contraindications to anticoagulation, the overall rate of pharmacologic thromboprophylaxis was 74.2% (95% CI, 70.4% to 78.0%; 392 of 528 patients). Among the patients with cancer without contraindications for anticoagulation, individuals hospitalized with nonhematologic malignancies were significantly more likely to receive pharmacologic thromboprophylaxis than those with hematologic malignancies (odds ratio [OR], 2.34; 95% CI, 1.43 to 3.82; P=.007). Patients with cancer admitted for cancer therapy were significantly less likely to receive pharmacologic thromboprophylaxis than those admitted for other reasons (OR, 0.37; 95% CI, 0.22 to 0.61; P<.001). Sixty-three percent of patients with cancer classified as low risk, as determined by the Padua Scoring System, received anticoagulant thromboprophylaxis. Among the 136 patients who did not receive anticoagulation, 58.8% were considered to be high risk by the Padua Scoring System.

Conclusion: We conclude that pharmacologic thromboprophylaxis is frequently administered to hospitalized patients with cancer but that nearly one third of patients are considered to have relative contraindications for prophylactic anticoagulation. Pharmacologic thromboprophylaxis in hospitalized patients with cancer is commonly prescribed without regard to the presence or absence of concomitant risk factors for VTE.
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http://dx.doi.org/10.1200/JCO.2013.53.5336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039867PMC
June 2014

Safety and feasibility of a diagnostic algorithm combining clinical probability, d-dimer testing, and ultrasonography for suspected upper extremity deep venous thrombosis: a prospective management study.

Ann Intern Med 2014 Apr;160(7):451-7

Background: Although well-established for suspected lower limb deep venous thrombosis, an algorithm combining a clinical decision score, d-dimer testing, and ultrasonography has not been evaluated for suspected upper extremity deep venous thrombosis (UEDVT).

Objective: To assess the safety and feasibility of a new diagnostic algorithm in patients with clinically suspected UEDVT.

Design: Diagnostic management study. (ClinicalTrials.gov: NCT01324037) SETTING: 16 hospitals in Europe and the United States.

Patients: 406 inpatients and outpatients with suspected UEDVT.

Measurements: The algorithm consisted of the sequential application of a clinical decision score, d-dimer testing, and ultrasonography. Patients were first categorized as likely or unlikely to have UEDVT; in those with an unlikely score and normal d-dimer levels, UEDVT was excluded. All other patients had (repeated) compression ultrasonography. The primary outcome was the 3-month incidence of symptomatic UEDVT and pulmonary embolism in patients with a normal diagnostic work-up.

Results: The algorithm was feasible and completed in 390 of the 406 patients (96%). In 87 patients (21%), an unlikely score combined with normal d-dimer levels excluded UEDVT. Superficial venous thrombosis and UEDVT were diagnosed in 54 (13%) and 103 (25%) patients, respectively. All 249 patients with a normal diagnostic work-up, including those with protocol violations (n = 16), were followed for 3 months. One patient developed UEDVT during follow-up, for an overall failure rate of 0.4% (95% CI, 0.0% to 2.2%).

Limitations: This study was not powered to show the safety of the substrategies. d-Dimer testing was done locally.

Conclusion: The combination of a clinical decision score, d-dimer testing, and ultrasonography can safely and effectively exclude UEDVT. If confirmed by other studies, this algorithm has potential as a standard approach to suspected UEDVT.

Primary Funding Source: None.
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http://dx.doi.org/10.7326/M13-2056DOI Listing
April 2014

Massive, rapidly growing cardiac lymphoma with rare valvular involvement showing excellent response to chemotherapy.

Can J Cardiol 2013 Sep 18;29(9):1139.e3-4. Epub 2013 Apr 18.

Division of Cardiovascular Medicine, University of Louisville, Louisville, KY 40202, USA.

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http://dx.doi.org/10.1016/j.cjca.2013.01.019DOI Listing
September 2013

Probable carvedilol-induced thrombocytopenia.

Am J Health Syst Pharm 2013 Apr;70(7):598-602

Department of Pharmacy, Veterans Affairs Medical Center, 50 Irving Street NW, Washington, DC 20422, USA.

Purpose: A case of probable carvedilol-induced thrombocytopenia is reported.

Summary: A 64-year-old African-American woman with a history of hypertension, diastolic dysfunction, mild left-ventricular hypertrophy, and pulmonary embolism was hospitalized with a platelet count of 94,000 platelets/mm(3). Dalteparin, warfarin, and carvedilol had recently been added to her medication regimen. Beta-2-glycoprotein immunoglobulin G (IgG) antibody, anticardiolipin IgG, and anticardiolipin immunoglobulin M tests, conducted to rule out antiphospholipid syndrome, revealed values within the normal range. After the exclusion of dalteparin, hydrochlorothiazide, and other causes of drug- and non-drug-related thrombocytopenia, carvedilol was discontinued and replaced with metoprolol tartrate. After this substitution, the patient's platelet count continued to rise. On hospital day 10, the patient was discharged to home on low-molecular-weight heparin bridging therapy, warfarin sodium 5 mg orally daily, ranitidine 150 mg orally daily, metoprolol tartrate 75 mg orally twice daily, lisinopril 20 mg orally daily, amlodipine 10 mg orally daily, cyanocobalamin 1000 mg orally daily, and two tablets of hydrochlorothiazide 25 mg-triamterene 37.5 mg orally daily. Her platelet count was 319,000 platelets/mm(3) on the day of discharge and remained stable thereafter. The recovery time of the platelets coincided with the elimination half-life of carvedilol.

Conclusion: A woman developed thrombocytopenia, first noticed as a reduction in the platelet count to a low-normal value, 17 days after treatment with carvedilol was begun. Other possible culprit drugs were withdrawn, but the platelet count continued to drop until carvedilol was discontinued. The platelet count rose on the day of carvedilol removal and was within the normal range within another day.
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http://dx.doi.org/10.2146/ajhp120383DOI Listing
April 2013

A woman with rheumatoid arthritis, Sjögren's syndrome, leg ulcer, and significant weight loss.

Arthritis Care Res (Hoboken) 2012 May;64(5):785-92

Veterans Affairs Medical Center, 50 Irving Street, Washington, DC 20422, USA.

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http://dx.doi.org/10.1002/acr.21628DOI Listing
May 2012

Acute chest syndrome: sickle cell disease.

Eur J Haematol 2011 Sep 26;87(3):191-207. Epub 2011 Jul 26.

Department of Medicine, Division of Hematology/Oncology, Howard University, 2041 Georgia Ave. NW, Washington, DC 20060, USA.

Acute chest syndrome (ACS) is a common complication and reason for hospital admission in patients with sickle cell disease (SCD). It is also the most common cause of death in this patient population. Most of the time, the trigger for ACS in an individual patient cannot be identified. However, although infection is the most common identifiable cause for ACS, other important triggers are vaso-occlusive crisis (VOC) and asthma. This comprehensive review will focus on the pathogenesis, clinical characteristics, complications and treatment available to manage ACS. But importantly, this review will highlight new possible etiologies, with the goal of improving oxygenation and, therefore, a reduction in sickling and lung damage in this patient population.
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http://dx.doi.org/10.1111/j.1600-0609.2011.01647.xDOI Listing
September 2011

Complete blood count, measures of iron status and inflammatory markers in inner-city African Americans with undiagnosed hepatitis C seropositivity.

Clin Chim Acta 2010 May 1;411(9-10):653-6. Epub 2010 Feb 1.

Department of Medicine, Howard University College of Medicine, Washington, DC, USA.

Background: Hepatitis C virus (HCV) infection may be associated with thrombocytopenia and increased iron stores in patients receiving medical care. We aimed to determine how often changes in hematologic, iron metabolic and inflammatory markers occur in individuals with undiagnosed HCV in the community.

Methods: Inner-city African Americans (n=143) were recruited from the community according to reported ingestion of alcohol. They were divided broadly into those who drank more or less than 56 g alcohol/day as assessed by dietary questionnaire. HCV serology was determined and laboratory values were compared according to HCV seropositivity in analyses that adjusted for alcohol consumption.

Results: The prevalence of HCV seropositivity was 23% among men and 29% among women. Levels of hepatocellular enzymes were higher with HCV seropositivity (P<0.0001) but hemoglobin concentrations, white blood cell and platelet counts and serum ferritin concentrations did not differ. The globulin fraction of the serum protein concentration (P=0.002) was increased with HCV seropositivity as expected with chronic inflammation. However, erythrocyte sedimentation rate and serum iron and haptoglobin levels did not differ significantly according to HCV status. Furthermore, multivariate analysis revealed that C-reactive protein was decreased and transferrin concentration was increased with both HCV and alcohol consumption (P<0.014).

Conclusions: Previously undiagnosed HCV seropositivity has little effect on the complete blood count and body iron stores but appears to perturb the response to an inflammatory stimulus, causing reduced rather than increased circulating CRP concentrations and increased rather than decreased transferrin concentrations.
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http://dx.doi.org/10.1016/j.cca.2010.01.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2847047PMC
May 2010

Crystal structure of the Bacillus anthracis nucleoside diphosphate kinase and its characterization reveals an enzyme adapted to perform under stress conditions.

Proteins 2009 Aug;76(2):496-506

Central Drug Research Institute, Lucknow, India.

Nucleoside diphosphate kinases (Ndks) play an important role in a plethora of regulatory and metabolic functions. Inhibition of the B. anthracis Ndk mRNA results in the formation of nonviable aberrant spores. We report the characterization and crystal structure of the enzyme from B. anthracis nucleoside diphosphate kinase (BaNdk), the first from sporulating bacteria. The enzyme, although from a mesophilic source, is active at extremes of pH (3.5-10.5), temperature (10-95 degrees C) and ionic strength (0.25-4.0M NaCl). It exists as a hexamer that is composed of two SDS-stable trimers interacting in a back-to-back association; mutational analysis confirms that the enzyme is a histidine kinase. The high-resolution crystal structure reported here reveals an unanticipated change in the conformation of residues between 43 and 63 that also regulates substrate entry in other Ndks. A comparative structural analysis involving Ndks from seven mesophiles and three thermophiles has resulted in the delineation of the structure into relatively rigid and flexible regions. The analysis suggests that the larger number of intramolecular hydrogen bonds and to a lesser extent ionic interactions in BaNdk contributes to its high thermostability. Mutational analysis and Molecular Dynamics simulations were used to probe the role of a highly conserved Gly19 (present at the oligomeric interface in most of the Ndks). The results suggest that the mutation leads to a rigidification of those residues that facilitate substrate entry and consequently leads to a large reduction in the kinase activity. Overall, the enzyme characterization helps to understand its apparent adaptation to perform under stress conditions.
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http://dx.doi.org/10.1002/prot.22364DOI Listing
August 2009