Publications by authors named "Ami N Shah"

35 Publications

Outcomes of Laparoscopic Versus Open Ladd Procedures and Risk Factors for Conversion.

J Laparoendosc Adv Surg Tech A 2021 Jan 11. Epub 2021 Jan 11.

Division of Pediatric Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.

Malrotation is a common congenital anomaly that can lead to bowel obstruction and ischemia if not corrected with a Ladd procedure. Controversy exists between open and laparoscopic approaches. We sought to compare postoperative outcomes and determine risk factors for conversion to an open procedure. The National Surgical Quality Improvement Program (NSQIP)-Pediatric was used to identify patients undergoing Ladd procedures from 2013 to 2018. Propensity score matching was used to account for differences in patient characteristics between open and laparoscopically treated cohorts. Chi-square tests and adjusted logistic regression analysis were used to determine patient outcomes differences between treatment groups and factors associated with conversion. A total of 2437 patients were identified, 1889 (77.5%) open, 548 (22.5%) laparoscopic, and 193 (35.2%) laparoscopic converted to open. Patients undergoing laparoscopic compared with open procedures had shorter length of stay (5 versus 7 days,  < .001) and lower overall complication rates (13.1% versus 18.1%,  = .025), despite longer operative times (108.9 versus 93.7 minutes,  < .001). Patients requiring conversion were more likely to be younger, have an urgent/emergent case, sepsis/septic shock, and nutritional support requirement. After risk adjustment, laparoscopic Ladd procedure is associated with decreased complications and minimal operative time increases compared with an open approach. Risk factors associated with conversion should be considered during operative planning.
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http://dx.doi.org/10.1089/lap.2020.0712DOI Listing
January 2021

The Use of Serial Circulating Tumor DNA to Detect Resistance Alterations in Progressive Metastatic Breast Cancer.

Clin Cancer Res 2021 Mar 15;27(5):1361-1370. Epub 2020 Dec 15.

Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Purpose: Circulating tumor DNA (ctDNA) is a promising tool for noninvasive longitudinal monitoring of genomic alterations. We analyzed serial ctDNA to characterize genomic evolution in progressive metastatic breast cancer.

Experimental Design: This was a retrospective cohort between 2015 and 2019 obtained under an Institutional Review Board-approved protocol at Northwestern University (Chicago, IL). ctDNA samples were analyzed with Guardant360 next-generation sequencing (NGS) assay. A total of 86 patients had at least two serial ctDNA collections with the second drawn at first post-NGS progression (PN1) by imaging and clinical assessment. A total of 27 participants had ctDNA drawn at second post-NGS clinical progression (PN2). We analyzed alterations, mutant allele frequency (MAF), number of alterations (NOA), and sites of disease on imaging in close proximity to ctDNA evaluation. Matched pairs' variations in MAF, NOA, and alterations at progression were tested through Wilcoxon test. We identified an independent control cohort at Massachusetts General Hospital (Boston, MA) of 63 patients with serial ctDNA sampling and no evidence of progression.

Results: We identified 44 hormone receptor-positive, 20 HER2, and 22 triple-negative breast cancer cases. The significant alterations observed between baseline and PN1 were ( < 0.0075), ( < 0.0126), ( < 0.0126), ( < 0.0455), and ( < 0.0143). Paired analyses revealed increased MAF and NOA from baseline to PN1 ( = 0.0026, and < 0.0001, respectively). When compared with controls without progression, patients with ctDNA collection at times of progression were associated with increased MAF and NOA ( = 0.0042 and < 0.0001, respectively).

Conclusions: Serial ctDNA testing identified resistance alterations and increased NOA and MAF were associated with disease progression. Prospective longitudinal ctDNA evaluation could potentially monitor tumor genomic evolution.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-1566DOI Listing
March 2021

Understanding the organ tropism of metastatic breast cancer through the combination of liquid biopsy tools.

Eur J Cancer 2021 Jan 8;143:147-157. Epub 2020 Dec 8.

Department of Medicine-Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. Electronic address:

Background: Liquid biopsy provides real-time data about prognosis and actionable mutations in metastatic breast cancer (MBC). The aim of this study was to explore the combination of circulating tumour DNA (ctDNA) analysis and circulating tumour cells (CTCs) enumeration in estimating target organs more susceptible to MBC involvement.

Methods: This retrospective study analysed 88 MBC patients characterised for both CTCs and ctDNA at baseline. CTCs were isolated through the CellSearch kit, while ctDNA was analysed using the Guardant360 NGS-based assay. Sites of disease were collected on the basis of imaging. Associations were explored both through uni- and multivariate logistic regression and Fisher's exact test and the random forest machine learning algorithm.

Results: After multivariate logistic regression, ESR1 mutation was the only significant factor associated with liver metastases (OR 8.10), while PIK3CA was associated with lung localisations (OR 3.74). CTC enumeration was independently associated with bone metastases (OR 10.41) and TP53 was associated with lymph node localisations (OR 2.98). The metastatic behaviour was further investigated through a random forest machine learning algorithm. Bone involvement was described by CTC enumeration and alterations in ESR1, GATA3, KIT, CDK4 and ERBB2, while subtype, CTC enumeration, inflammatory BC diagnosis, ESR1 and KIT aberrations described liver metastases. PIK3CA, MET, AR, CTC enumeration and TP53 were associated with lung organotropism. The model, moreover, showed that AR, CCNE1, ESR1, MYC and CTC enumeration were the main drivers in HR positive MBC metastatic pattern.

Conclusions: These results indicate that ctDNA and CTCs enumeration could provide useful insights regarding MBC organotropism, suggesting a possible role for future monitoring strategies that dynamically focus on high-risk organs defined by tumourbiology.
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http://dx.doi.org/10.1016/j.ejca.2020.11.005DOI Listing
January 2021

Appendicitis Within a Pseudocyst: Rare Presentation in a Child With a Ventriculoperitoneal Shunt.

Am Surg 2020 Nov 11:3134820940628. Epub 2020 Nov 11.

Department of Surgery, Division of Pediatric Surgery Rush University Medical Center, Chicago, IL, USA.

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http://dx.doi.org/10.1177/0003134820940628DOI Listing
November 2020

Silo placement in gastroschisis: A pilot study of simulation-based training for general surgery residents.

J Pediatr Surg 2020 Oct 6. Epub 2020 Oct 6.

Division of Pediatric Surgery, Department of Surgery, Rush University Medical Center, 1750 W. Harrison, Suite 785, Chicago, IL, 60612, USA. Electronic address:

Introduction: General surgery residents often feel unprepared for rotations on pediatric surgical services as case volume and experience performing pediatric procedures may be inadequate for high acuity, low volume procedures. We designed a single institution pilot study to assess whether simulation-based training (SBT) for placement of a silastic silo for gastroschisis was feasible and lead to skill acquisition, retention and increased resident confidence.

Methods: We used our newly created gastroschisis module within our pediatric surgery SBT curriculum for general surgery residents. Residents completed two simulation sessions three months apart, completed confidence testing before and after each session, and were assessed using a standardized case scenario and procedure checklist. Wilcoxon Signed-Rank Tests evaluated changes in residents' confidence and performance.

Results: Ten post-graduate-year three general surgery residents completed this curriculum. Residents reported improved confidence completing each step of the procedure initially (p=0.008) and at 3 months (p=0.005). They had improved technical scores across all steps of the procedure (p=0.005). The number of residents deemed proficient significantly improved (p=0.008).

Conclusion: We demonstrated the feasibility of assessing the technical skills of general surgery residents performing a simulated placement of a silastic silo for gastroschisis. Residents' confidence and proficiency improved over the three-month period.

Study Type: Prospective LEVEL OF EVIDENCE: Level II.
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http://dx.doi.org/10.1016/j.jpedsurg.2020.09.063DOI Listing
October 2020

Risk-based Approaches for Optimizing Treatment in HER2-Positive Early Stage Breast Cancer.

Semin Oncol 2020 Oct 20;47(5):249-258. Epub 2020 Aug 20.

Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois. Electronic address:

Advancements in the care for patients with early stage HER2-positive breast cancer is a story of incremental successes aimed at optimizing efficacy and reducing the toxicities of administered therapies. HER2 drives an aggressive breast cancer subtype that represents 15%-20% of breast cancers, for which HER2-targeted therapy is very active. In addition to trastuzumab, pertuzumab, neratinib, and ado-trastuzumab emtansine have been approved in recent years for the treatment of high-risk early stage HER2-positive breast cancer. As a result of both a high response rate to neoadjuvant therapy and the opportunity for response-adapted adjuvant therapy, the treatment paradigm has evolved so that most patients with stage II and III disease now receive neoadjuvant therapy. Additionally, the efficacy of HER2-therapy allows for de-escalation of treatment in many patients with stage I disease. As a result, multidisciplinary evaluation is essential for the optimal care of patients with HER2-positive breast cancer. Important areas of further research include tailoring the duration and intensity of therapy based on disease risk and response to neoadjuvant therapy. This article will review the evaluation of patients with early stage HER2-positive breast cancer and provide an evidence- and guideline-based summary of risk-based treatment strategies.
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http://dx.doi.org/10.1053/j.seminoncol.2020.07.007DOI Listing
October 2020

Landscape of circulating tumour DNA in metastatic breast cancer.

EBioMedicine 2020 Aug 21;58:102914. Epub 2020 Jul 21.

Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, 710N. Fairbanks Court- Olson Pavilion, Suite 8-250A, Chicago, IL 60611, United States. Electronic address:

Background: We describe the genomic landscape of circulating tumour DNA (ctDNA) across pathological subtypes of metastatic breast cancer.

Methods: 255 clinically annotated patients with ctDNA testing by Guardant360 were stratified into HR+, HER2+, and TNBC cohorts. Frequency and heterogeneity of alterations were reported. Paired ctDNA and tissue sequencing were compared for a subset of patients. The association of ctDNA and metastatic sites of disease on imaging was also assessed.

Findings: 89% of patients had at least one ctDNA alteration detected. The most common single nucleotide variants (SNVs) for HR+ patients were PIK3CA, ESR1, and TP53. For HER2+, these were TP53, PIK3CA, and ERBB2 with ERBB2 as the most frequent copy number variant (CNV). For TNBC, the most common SNVs were TP53 and PIK3CA, and the most frequent CNVs were MYC, CCNE1, and PIK3CA. TNBC patients had a significantly higher mutant allele frequency (MAF) of the highest variant compared to HR+ or HER2+ patients (P<0.05). Overall, alterations in PIK3CA, ESR1, and ERBB2 were observed in 39.6%, 16.5%, and 21.6% of patients, respectively. Agreement between blood and tissue was 79-91%. MAF and number of alterations were significantly associated with number of metastatic sites on imaging (P<0.0001).

Interpretation: These data demonstrate the genetic heterogeneity of metastatic breast cancer in blood, the high prevalence of clinically actionable alterations, and the potential to utilise ctDNA as a surrogate for tumour burden on imaging.

Funding: Lynn Sage Cancer Research Foundation, OncoSET Precision Medicine Program, and REDCap support was funded by the National Institutes of Health UL1TR001422.
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http://dx.doi.org/10.1016/j.ebiom.2020.102914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381501PMC
August 2020

Early Diagnosis and Treatment of Chylous Mesenteric Cysts.

Am Surg 2020 Sep 19;86(9):1205-1207. Epub 2020 Jun 19.

2461 Division of Pediatric Surgery, Department of Surgery, Rush University Medical center, Chicago, IL, USA.

Mesenteric cysts are benign congenital cysts typically discovered incidentally during abdominal explorations for other reasons. When feasible, they should be excised to prevent recurrence, bowel obstruction or volvulus, and resulting complications. We present a unique case of an infant, diagnosed prenatally by ultrasound with possible bowel obstruction, found to have micro and macro chylous mesenteric cysts. Although initially asymptomatic with normal abdominal x-ray and discharged on day of life 2, the parents were taught how to recognize symptoms of bowel obstruction. He presented at 1 month with obstructive symptoms, was confirmed to have large mesenteric cystic structures on ultrasound, and was immediately taken to the operating room. Due to the extensive number of cysts and intimate involvement of the largest cyst with the superior mesenteric artery, he was treated with partial excision and observation since resection may have resulted in short gut syndrome. Given a prenatal ultrasound suggestive of mesenteric cysts, we recommend abdominal imaging at birth with close follow-up until the appropriate time for elective resection. When disease is extensive precluding full enucleation and resection, we advocate for enucleation in combination with unroofing of as many cysts as possible followed by postoperative surveillance ultrasounds and family counseling.
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http://dx.doi.org/10.1177/0003134820933603DOI Listing
September 2020

Pediatric Surgery Simulation-Based Training for the General Surgery Resident.

J Surg Res 2021 02 16;258:339-344. Epub 2020 Jun 16.

Division of Pediatric Surgery, Department of Surgery, Rush University Medical Center, Chicago, Illinois; Rush Center For Clinical Skills and Simulation, Rush University Medical Center, Chicago, Illinois.

Background: Surgical simulation-based training (SBT) can increase resident confidence and improve performance. SBT in pediatric surgery is in its infancy and often geared toward training pediatric surgery fellows. Since case volume for various pediatric surgery-specific procedures can be low based on the rarity of the pathology involved and the level of care provided by the institution, our aim was to create a pediatric surgery simulation-based curriculum for general surgery residents to address this need.

Materials And Methods: We performed an institutional needs assessment consisting of 4 pediatric surgeons' and 28 general surgery residents' confidence in resident ability to independently perform pediatric surgery-specific tasks and procedures using a Likert-scaled survey. These included the placement of a silastic silo for gastroschisis, a percutaneous drain for perforated necrotizing enterocolitis, and completion of a laparoscopic pyloromyotomy for pyloric stenosis. Models simulating these pathologies and curriculum for performing each procedure were generated.

Results: We successfully created a model and SBT curriculum to teach general surgery residents how to place a silastic silo for patients with gastroschisis, a percutaneous drain for patients with perforated necrotizing enterocolitis, and how to complete a laparoscopic pyloromyotomy for patients with pyloric stenosis. These were deemed high fidelity models based on a survey of our pediatric surgeons.

Conclusions: We created a pediatric surgery SBT curriculum for general surgery residents, which can be used to supplement learning of various high-acuity, low-occurrence procedures. Assessment of residents and validation of scores is underway.
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http://dx.doi.org/10.1016/j.jss.2020.05.038DOI Listing
February 2021

The influence of prematurity on neonatal surgical morbidity and mortality.

J Pediatr Surg 2020 Dec 1;55(12):2608-2613. Epub 2020 Apr 1.

Division of Pediatric Surgery, Department of Surgery, Northwestern University Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, 60611, USA. Electronic address:

Background: As survival rates amongst premature infants have improved, prematurity remains a leading contributor to neonatal surgical morbidity and mortality. This study aims to better assess the influence of prematurity on surgical outcomes.

Methods: The NSQIP-Pediatric database was used to compare outcomes between preterm and term infants undergoing surgical repair of select congenital anomalies from 2012 to 2017. Prematurity was categorized as extremely preterm (EP) (<29 weeks), very preterm (VP) (29-32 weeks), moderate to late preterm (MLP) (33-36 weeks), and term (≥37 weeks). Significance was determined using Chi-square tests, Fisher exact tests and adjusted logistic regression analysis.

Results: 4852 infants were identified with 45 (0.9%) EP, 211 (4.3%) VP, 1492 (30.8%) MLP, and 3104 (64.0%) term. Compared to term, preterm infants have increased odds of surgical morbidity (EP Odds Ratio (OR) 3.2 95% Confidence Interval (CI) 1.6-6.4, VP OR 1.2 95%CI 0.9-1.7, and MLP OR 1.2 95%CI 1.0-1.4). 30-day mortality decreased as neonatal age increased from 22.2% EP to 2.9% term (p < 0.001). Premature populations had higher rates of sepsis, pneumonia, bleeding requiring transfusion and 30-day mortality.

Conclusions: Prematurity increases morbidity and mortality amongst neonates undergoing surgery. Risk-adjustment for prematurity is needed and premature infants may have unique quality improvement targets.

Level Of Evidence: Level III.
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http://dx.doi.org/10.1016/j.jpedsurg.2020.03.024DOI Listing
December 2020

Hormone Receptor-Positive/Human Epidermal Growth Receptor 2-Negative Metastatic Breast Cancer in Young Women: Emerging Data in the Era of Molecularly Targeted Agents.

Oncologist 2020 06 16;25(6):e900-e908. Epub 2020 Mar 16.

Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Breast cancer is the most common malignancy in young women worldwide, accounting for an estimated 30% of new cancer diagnoses and 25% of cancer deaths. Approximately two thirds of young women with breast cancer have hormone receptor-positive (HR+)/human epidermal growth receptor 2-negative (HER2-) tumors. Numerous studies, primarily in early-stage breast cancer, have demonstrated that young age is an independent risk factor for more aggressive disease and worse outcomes. Although more limited data are available regarding outcomes in young patients with advanced disease, these age-related disparities suggest that breast cancer in premenopausal women has distinct clinicopathologic and molecular features that can impact treatment outcomes. Until recently, limited data were available on the intrinsic molecular subtypes and genetics of young patients with HR+/HER2- metastatic breast cancer (mBC). In this review, we explore insights into the clinical and pathologic features of HR+/HER2- mBC in younger women derived from recent clinical trials of the cyclin-dependent kinase 4/6 inhibitors palbociclib (PALOMA-3), ribociclib (MONALEESA-7), and abemaciclib (MONARCH 2) and the implications of these findings for clinical practice, guideline development, and future research. IMPLICATIONS FOR PRACTICE: This review provides clinicians with an overview of emerging data on the unique clinicopathologic and molecular features of hormone receptor-positive/human epidermal growth receptor 2-negative metastatic breast cancer (mBC) in premenopausal women, summarizes findings from the most recent clinical trials of endocrine-based treatment in this patient population, and explores the implications of these findings for clinical practice, guideline development, and future research. Improved understanding of the key factors influencing disease course and treatment response in premenopausal patients with mBC may lead to more timely incorporation of evidence-based treatment approaches, thereby improving patient care and outcomes.
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http://dx.doi.org/10.1634/theoncologist.2019-0729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288640PMC
June 2020

Phase II study of pembrolizumab and capecitabine for triple negative and hormone receptor-positive, HER2-negative endocrine-refractory metastatic breast cancer.

J Immunother Cancer 2020 02;8(1)

Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA.

Background: Response rates to single agent immune checkpoint blockade in unselected pretreated HER2-negative metastatic breast cancer (MBC) are low. However, they may be augmented when combined with chemotherapy.

Methods: We conducted a single-arm, phase II study of patients with triple negative (TN) or hormone receptor-positive endocrine-refractory (HR+) MBC who were candidates for capecitabine. Patients were treated with pembrolizumab 200 mg intravenously day 1 and capecitabine 1000 mg/m by mouth twice daily on days 1-14 of a 21-day cycle. The primary end point was median progression-free survival (mPFS) compared with historic controls and secondary end points were overall response rate (ORR), safety and tolerability. The study had 80% power to detect a 2-month improvement in mPFS with the addition of pembrolizumab over historic controls treated with capecitabine alone.

Results: Thirty patients, 16 TN and 14 HR+ MBC, were enrolled from 2017 to 2018. Patients had a median age of 51 years and received a median of 1 (range 0-6) prior lines of therapy for MBC. Of 29 evaluable patients, the mPFS was 4.0 (95% CI 2.0 to 6.4) months and was not significantly longer than historic controls of 3 months. The median overall survival was 15.4 (95% CI 8.2 to 20.3) months. The ORR was 14% (n=4), stable disease (SD) was 41% (n=12) and clinical benefit rate (CBR=partial response+SD>6 months) was 28% (n=8). The ORR and CBR were not significantly different between disease subtypes (ORR 13% and 14%, CBR 25% and 29% for TN and HR+, respectively). The 1-year PFS rate was 20.7% and three patients have ongoing responses. The most common adverse events were low grade and consistent with those seen in MBC patients receiving capecitabine, including hand-foot syndrome, gastrointestinal symptoms, fatigue and cytopenias. Toxicities at least possibly from pembrolizumab included grade 3 or 4 liver test abnormalities (7%), rash (7%) and diarrhea (3%), as well as grade 5 hepatic failure in a patient with liver metastases.

Conclusions: Compared with historical controls, pembrolizumab with capecitabine did not improve PFS in this biomarker unselected, pretreated cohort. However, some patients had prolonged disease control.

Trial Registration Number: NCT03044730.
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http://dx.doi.org/10.1136/jitc-2019-000173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057426PMC
February 2020

Mother's own milk dose is associated with decreased time from initiation of feedings to discharge and length of stay in infants with gastroschisis.

J Perinatol 2020 08 28;40(8):1222-1227. Epub 2020 Jan 28.

Section of Neonatology, Department of Pediatrics, Rush University Medical Center, Chicago, IL, 60612, USA.

Objective: To determine if mother's own milk (MOM) dose after gastroschisis repair is associated with time from feeding initiation to discharge. Secondary outcomes included parenteral nutrition (PN) duration and length of stay (LOS).

Study Design: Retrospective study of 44 infants with gastroschisis examined demographics, gastroschisis type, PN days, timing of nutrition milestones, feeding composition, and LOS.

Results: MOM dose was significantly associated with shorter time to discharge from feeding initiation (adjusted hazard ratio [HR] for discharge per 10% increase in MOM dose, 1.111; 95% CI, 1.011-1.220, p = 0.029). MOM dose was also significantly associated with shorter LOS (adjusted HR for discharge per 10% increase in MOM dose, 1.130; 95% CI, 1.028-1.242, p = 0.011).

Conclusions: MOM dose was significantly associated with a decrease in time to discharge from feeding initiation and LOS in a dose-dependent manner. Mothers of gastroschisis patients should receive education and proactive lactation support to optimize MOM volume for feedings.
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http://dx.doi.org/10.1038/s41372-020-0595-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223788PMC
August 2020

Association of a novel circulating tumor DNA next-generating sequencing platform with circulating tumor cells (CTCs) and CTC clusters in metastatic breast cancer.

Breast Cancer Res 2019 12 4;21(1):137. Epub 2019 Dec 4.

Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Purpose: Liquid biopsies, including circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs), can be used to understand disease prognosis, tumor heterogeneity, and dynamic response to treatment in metastatic breast cancer (MBC). We explored a novel, 180-gene ctDNA panel and the association of this platform with CTCs and CTC clusters.

Methods: A total of 40 samples from 22 patients with MBC were included in the study. For the primary analysis, all patients had ctDNA sequencing using the PredicinePLUS™ platform. CTCs and CTC clusters were examined using the CellSearch™ System. Clinical and pathological variables were reported using descriptive analyses. Associations between CTC count and specific genomic alterations were tested using the Mann-Whitney U test.

Results: Of 43 sequenced patients, 40 (93%) had at least one detectable genomic alteration with a median of 6 (range 1-22). Fifty-seven different genes were altered, and the landscape of genomic alterations was representative of MBC, including the commonly encountered alterations TP53, PTEN, PIK3CA, ATM, BRCA1, CCND1, ESR1, and MYC. In patients with predominantly hormone-receptor-positive MBC, the number of CTCs was significantly associated with alterations in ESR1 (P < 0.005), GATA3 (P < 0.05), CDH1 (P < 0.0005), and CCND1 (P < 0.05) (Mann-Whitney U test). Thirty-six percent of patients had CTC clusters, which were associated with alterations in CDH1, CCND1, and BRCA1 (all P < 0.05, Mann-Whitney U test). In an independent validation cohort, CTC enumeration confirmed significant associations with ESR1 and GATA3, while CTC clusters were significantly associated with CDH1.

Conclusions: We report on a novel ctDNA platform that detected genomic alterations in the vast majority of tested patients, further indicating potential clinical utility for capturing disease heterogeneity and for disease monitoring. Detection of CTCs and CTC clusters was associated with particular genomic profiles.
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http://dx.doi.org/10.1186/s13058-019-1229-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894208PMC
December 2019

Emerging Role of Genomics and Cell-Free DNA in Breast Cancer.

Curr Treat Options Oncol 2019 06 29;20(8):68. Epub 2019 Jun 29.

Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, 710 N Fairbanks Court, Suite 8-250A, Chicago, IL, 60611, USA.

Opinion Statement: Precision Medicine is gaining momentum as the future gold standard healthcare strategy as it enables treatment optimization and consequently a potential improvement for quality of life and survival. This paradigm shift was possible thanks to new high-throughput genomics technologies, which provide prognostic and predictive information on tumor biology and potential treatment options, as standard pathological procedures are unable to capture both spatial and temporal tumor heterogeneity. As a result of decreasing costs, both solid and liquid-based genomics have an increasingly important role in clinical trials' screening procedures and are gradually being incorporated into clinical practice. Notwithstanding the great potential, its clinical utility is still a matter of debate and clinicians need to be aware of caveats in interpreting resulting data.
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http://dx.doi.org/10.1007/s11864-019-0667-9DOI Listing
June 2019

Adjuvant Anthracyclines in Breast Cancer: What Is Their Role?

Oncologist 2018 10 17;23(10):1153-1161. Epub 2018 Aug 17.

Lynn Sage Breast Cancer Program, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA

Anthracyclines have been a mainstay of breast cancer therapy for decades, with strong evidence demonstrating their impact on breast cancer survival. However, concerns regarding rare but serious long-term toxicities including cardiotoxicity and hematologic malignancies have driven interest in alternative adjuvant therapy options with more favorable toxicity profiles. This article provides an update of data that help inform clinicians of the role anthracyclines should play in adjuvant breast cancer therapy. Two recently reported large randomized trials-the Anthracycline in Early Breast Cancer and Western German Study Plan B studies-compared a taxane and cyclophosphamide regimen with an anthracycline, taxane, and cyclophosphamide regimen. Although the studies had conflicting results, together these studies suggest that the benefit of adjuvant anthracycline therapy over a nonanthracycline taxane-containing regimen is modest at best and may be primarily seen in patients with especially high-risk disease (i.e., triple-negative breast cancer, involvement of multiple lymph nodes). A third study-the MINDACT study-compared an anthracycline-based regimen to a nonanthracycline regimen, with similar outcomes in both groups. Despite the toxicities, no adjuvant breast cancer regimen has been shown to be superior to an anthracycline-taxane regimen in high-risk patients. These data can directly inform clinical decision-making in determining which patients warrant use of adjuvant anthracycline therapy. Future research may focus on confirming subgroups for whom it is reasonable to forgo adjuvant anthracyclines and validating predictive biomarkers or scores for anthracycline benefit.

Implications For Practice: In patients with early breast cancer, the choice of adjuvant chemotherapy should be based on its effectiveness in reducing breast cancer recurrences and its short- and long-term toxicities. Although adjuvant anthracycline and taxane chemotherapy has the most data supporting its effectiveness, anthracyclines carry a small but important increased risk for cardiotoxicity and leukemia. Two recent clinical trials help describe the degree of benefit with adjuvant anthracycline therapy compared with taxane therapy alone. They suggest that in patients with hormone receptor-positive breast cancer and limited lymph node involvement, nonanthracycline taxane-based adjuvant therapy may be adequate.
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http://dx.doi.org/10.1634/theoncologist.2017-0672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6263120PMC
October 2018

Phase I study of alpelisib (BYL-719) and trastuzumab emtansine (T-DM1) in HER2-positive metastatic breast cancer (MBC) after trastuzumab and taxane therapy.

Breast Cancer Res Treat 2018 Sep 30;171(2):371-381. Epub 2018 May 30.

Lynn Sage Breast Cancer Program, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, 676 N St. Clair St. Suite 850, Chicago, IL, 60611, USA.

Purpose: Activation of the phosphoinositide 3-kinase (PI3K) pathway is an important resistance mechanism to anti-HER2 therapies. This study aimed to assess the safety and activity of alpelisib (a PI3Kα isoform-specific inhibitor) with T-DM1 in trastuzumab- and taxane-resistant HER2-positive MBC.

Methods: Patients with HER2-positive MBC that had progressed on trastuzumab-based therapy were treated with alpelisib daily and T-DM1 3.6 mg/kg every 3 weeks. The dose-limiting toxicity (DLT), maximum tolerated dose (MTD), adverse events, overall response rate (ORR), and clinical benefit rate (CBR = CR + PR + SD > 6 months) were assessed with descriptive statistics. Progression-free survival (PFS) was calculated by the Kaplan-Meier method.

Results: Seventeen patients were enrolled with a median of 3 prior therapies for metastatic disease. The DLT was a maculopapular rash and MTD was 250 mg alpelisib daily. The most frequently occurring toxicities included fatigue, rash, gastrointestinal side effects, thrombocytopenia, anemia, elevated liver enzymes, and hyperglycemia. Fourteen patients were evaluable for response with an ORR of 43%. In patients with prior treatment and progression on T-DM1 (n = 10), the ORR was 30%. The CBR was 71% in evaluable patients and 60% in those with prior T-DM1. The median PFS was 8.1 months.

Conclusions: The combination of alpelisib and T-DM1 is tolerable and demonstrates activity in trastuzumab-resistant HER2-positive MBC. Furthermore, activity was observed in T-DM1-resistant disease. These data suggest that PIK3CA inhibition targets an important resistance pathway to anti-HER2 therapy, providing rationale for further study of PI3K inhibition in refractory HER2-positive MBC to validate these results.
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http://dx.doi.org/10.1007/s10549-018-4792-0DOI Listing
September 2018

A pilot study of durvalumab and tremelimumab and immunogenomic dynamics in metastatic breast cancer.

Oncotarget 2018 Apr 10;9(27):18985-18996. Epub 2018 Apr 10.

Northwestern University, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois, USA.

Immune checkpoint inhibitors produce modest responses in metastatic breast cancer, however, combination approaches may improve responses. A single arm pilot study was designed to determine the overall response rate (ORR) of durvalumab and tremelimumab, and evaluate immunogenomic dynamics in metastatic endocrine receptor (ER) positive or triple negative breast cancer (TNBC). Simon two-stage design indicated at least four responses from the first 18 patients were needed to proceed with the second stage. T-cell receptor (TCR) sequencing and immune-gene expression profiling were conducted at baseline and two months, whole exome sequencing was conducted at baseline. Eighteen evaluable patients were accrued (11 ER-positive; seven TNBC). Only three patients had a response (ORR = 17%), thus the study did not proceed to the second stage. Responses were only observed in patients with TNBC (ORR = 43%). Responders versus non-responders had upregulation of , , and gene expression, and higher mutational and neoantigen burden. Patients with TNBC had an oligoclonal shift of the most abundant TCR-beta clonotypes compared to those with ER-positive disease, = 0.004. We conclude responses are low in unselected metastatic breast cancer, however, higher rates of clinical benefit were observed in TNBC. Immunogenomic dynamics may help identify phenotypes most likely to respond to immunotherapy.
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http://dx.doi.org/10.18632/oncotarget.24867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922371PMC
April 2018

Anaplastic Lymphoma Kinase Mutation ( F1174C) in Small Cell Carcinoma of the Prostate and Molecular Response to Alectinib.

Clin Cancer Res 2018 06 20;24(12):2732-2739. Epub 2018 Mar 20.

The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Small cell carcinoma of the prostate (SCCP) is an aggressive disease that can arise or by transdifferentiation from prostate adenocarcinoma. Alterations in anaplastic lymphoma kinase () gene are involved in neuroblastoma, lung cancer, and other malignancies, but its role in SCCP has not been documented. We describe a patient with refractory SCCP with F1174C-activating mutation who obtained clinical benefit from treatment with ALK inhibitor. Next-generation sequencing (NGS) was used to analyze primary and circulating tumor DNA (ctDNA). Prostate cancer databases were queried for alterations in gene, mRNA, and its impact in clinical outcomes. prostate cell line/organoid models were generated by lentiviral-mediated expression of ALK and ALK F1174C and assessed for response to ALK inhibitors crizotinib and alectinib. NGS analysis of the primary tumor and ctDNA of a 39-year-old patient with refractory SSCP identified F1174C mutation. Treatment with second-generation ALK inhibitor alectinib resulted in radiographic stable disease for over 6 months, symptomatic improvement, and significant molecular response as reflected by declining ctDNA allele fraction. Analysis of prostate cancer datasets showed that amplification was associated with poor outcome. In prostate cancer cells and organoids, F1174C expression enhanced growth and induced expression of the neuroendocrine marker neuron-specific enolase. Alectinib was more effective than crizotinib in inhibiting F1174C-expressing cell growth. These findings implicate -activating mutations in SCCP pathogenesis and suggest the therapeutic potential of targeting molecular alterations in some patients with SCCP. .
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http://dx.doi.org/10.1158/1078-0432.CCR-18-0332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715284PMC
June 2018

The Growing Role of CDK4/6 Inhibitors in Treating Hormone Receptor-Positive Advanced Breast Cancer.

Curr Treat Options Oncol 2017 01;18(1)

Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, 710 North Fairbanks Ct, Suite 8-250a, Chicago, IL, USA.

Opinion Statement: Single-agent endocrine therapy has been the standard therapeutic choice for the management of hormone receptor (HR)-positive, Her2-negative advanced breast cancer (ABC) for decades. However, the rapidly accumulating data regarding the biological role and safety of CDK4/6 inhibitors and the first-in-class approval of palbociclib have made these novel agents an essential component of treatment for HR-positive ABC. In the frontline setting, palbociclib in combination with endocrine therapy showed an improvement in progression-free survival (PFS) by 10 months to nearly 25 months when compared with endocrine therapy alone and a clinical benefit rate (CBR = stable disease >24 weeks + partial response + complete response) of 85%. Furthermore, clinically meaningful improvements in PFS were seen in combination with fulvestrant for patients with prior endocrine therapy, including premenopausal women. While neutropenia is experienced by most patients, it is typically uncomplicated and palbociclib is otherwise well tolerated. Recent analysis also demonstrated improved quality of life and reassuring evidence of no compromise in benefit from subsequent therapies after progression on palbociclib. Along with palbociclib, the CDK4/6 inhibitors ribociclib and abemaciclib are being evaluated in a variety of settings (metastatic, neoadjuvant, and adjuvant), alone and in combination with endocrine therapy, chemotherapy, and targeted therapies. Future research is needed to address challenges regarding the potential competition of these agents as the preferred partner in endocrine-sensitive disease, their use as single agents or in combination in the endocrine-refractory setting, and the clinical and molecular criteria for use as an alternative to chemotherapy. Unfortunately, despite efforts to determine predictive biomarkers for response, RB1 expression and HR-positive disease have been the only clear predictors of therapeutic benefit. Once more mature data become available, we hope to confirm a significant impact on long-term survival. Meanwhile, given the multiple therapies patients with ABC will receive, prolonged PFS with a well-tolerated oral regimen is a clinically meaningful endpoint. Palbociclib's impact on PFS, high CBR, and tolerability have made its use a preferred option for treating many HR-positive, Her2-negative ABC patients.
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http://dx.doi.org/10.1007/s11864-017-0443-7DOI Listing
January 2017

Targeting Epidermal Growth Factor Receptor in triple negative breast cancer: New discoveries and practical insights for drug development.

Cancer Treat Rev 2017 Feb 5;53:111-119. Epub 2017 Jan 5.

Developmental Therapeutics Program, Division of Hematology/Oncology, Feinberg School of Medicine, Chicago, USA; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, USA.

Triple negative breast cancer (TNBC) accounts for 10-20% of cases in breast cancer. Despite recent advances in the treatment of hormonal receptor+ and HER2+ breast cancers, there are no targeted therapies available for TNBC. Evidence supports that most patients with TNBC express the transmembrane Epidermal Growth Factor Receptor (EGFR). However, early phase clinical trials failed to demonstrate significant activity of EGFR-targeted monoclonal antibodies and/or tyrosine kinase inhibitors. Here, we review the recent discoveries related to the underlying biology of the EGFR pathway in TNBC, clinical progress to date and suggest rational future approaches for investigational therapies in TNBC.
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http://dx.doi.org/10.1016/j.ctrv.2016.12.010DOI Listing
February 2017

Fetus in Fetu-A Case Report with a Variant Host Anastomosis.

Am Surg 2016 Sep;82(9):759-62

Rush University Medical Center, Chicago, Illinois, USA.

Fetus in fetu is a rare congenital condition where a vertebrate fetus is found within the body of its host twin. It features a monozygotic parasitic twin attached via a vascular anastomosis to its host circulation. This report describes an instance of fetus in fetu with a variant presentation of its vascular pedicle to its host via the inferior epigastric vasculature.
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September 2016

Early Closure of Gastroschisis After Silo Placement Correlates with Earlier Enteral Feeding.

J Neonatal Surg 2015 Jul-Sep;4(3):28. Epub 2015 Jul 1.

Division of Pediatric Surgery, Rush University Medical Center. 1653 W. Congress Parkway Jelke Suite 792, Chicago.

Objectives: Gastroschisis is a congenital anomaly affecting 2.3-4.4/10,000 births. Previous studies show initiation of early enteral feeds predicts improved outcomes. We hypothesize that earlier definitive closure after silo placement; can lead to earlier enteral feed initiation. Design/ Setting/ Duration: Retrospective review of patients with gastroschisis from 2005 and 2014 at a single institution.

Material And Methods: The data, including ethnicity, gestational age, birth weight, time to definitive closure, and time of first and full feeds, were analyzed using both Spearman's rho and the Kruskal-Wallis rank sum test where appropriate; a p value less than 0.05 was considered significant.

Results: Forty-three patients (24 males, 19 females) born with gastroschisis were identified. Overall survival rate was 88% (38/43). Forty of the 43 patients had a silo placed prior to definitive closure. Median days to closure were 6 (0 to 85) days. First feeds on average began on day of life (DOL) 17, and full feeds on DOL 25. Earlier closure of gastroschisis correlated with early initiation of feeds (p=0.0001) and shorter time to full feeds (p=0.018), closure by DOL4 showed a trend toward earlier feeding (p=0.13).

Conclusion: Earlier closure of gastroschisis after silo placement was associated with earlier feed initiation and shorter time to full feeds.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518187PMC
August 2015

An update on the risk prediction and prevention of anticancer therapy-induced cardiotoxicity.

Curr Opin Oncol 2014 Nov;26(6):590-9

aInternal Medicine Residents bMedicine-Cardiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois cComprehensive Cancer Center, City of Hope, Duarte, California, USA *Manali Bhave and Ami N. Shah contributed equally to the writing of this article.

Purpose Of Review: Cardiotoxicity is a well established complication of anticancer therapy. As cancer survivorship and life expectancy for cancer patients improves, the morbidity and mortality of anticancer therapy-related cardiotoxicity has become more problematic. It is of utmost importance to identify patients at the highest risk for the development of cardiotoxicity and to determine strategies for prevention, early detection and treatment.

Recent Findings: Clinical risk factors, biomarkers, advanced cardiac imaging and pharmacogenomics may be used to classify patients at risk for therapy-induced cardiotoxicity. A much broader armamentarium of imaging modalities for risk prediction, in addition to simple two-dimensional echocardiogram and radionucleotide angiography, has also shown clinical utility in identifying early-onset cardiotoxicity and areas of reversible myocardial injury. Exciting new research aimed at predicting cardiotoxicity and developing cardioprotective strategies may lead to changes in the administration of cardiotoxic chemotherapies.

Summary: Personalized assessments of the risks and benefits of therapy should be used as opposed to standardized dosing and schedules. Patients at higher risk for cardiotoxicity should receive closer monitoring, cardioprotective agents, dose adjustment or alternative regimens in an effort to reduce cardiovascular morbidity and mortality. Future research will hopefully define specific risk prediction tools and clinical protocols to prevent irreversible cardiotoxicity.
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http://dx.doi.org/10.1097/CCO.0000000000000132DOI Listing
November 2014

Designing effective drug and device development programs for hospitalized heart failure: a proposal for pretrial registries.

Am Heart J 2014 Aug 24;168(2):142-9. Epub 2014 May 24.

Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL. Electronic address:

Recent international phase III clinical trials of novel therapies for hospitalized heart failure (HHF) have failed to improve the unacceptably high postdischarge event rate. These large studies have demonstrated notable geographic and site-specific variation in patient profiles and enrollment. Possible contributors to the lack of success in HHF outcome trials include challenges in selecting clinical sites capable of (1) providing adequate numbers of appropriately selected patients and (2) properly executing the study protocol. We propose a "pretrial registry" as a novel tool for improving the efficiency and quality of international HHF trials by focusing on the selection and cultivation of high-quality sites. A pretrial registry may help assess a site's ability to achieve adequate enrollment of the target patient population, integrate protocol requirements into clinical workflow, and accomplish appropriate follow-up. Although such a process would be associated with additional upfront resource investment, this appropriation may be modest in comparison with the downstream costs associated with maintenance of poorly performing sites, failed clinical trials, and the global health and economic burden of HHF. This review is based on discussions between scientists, clinical trialists, and regulatory representatives regarding methods for improving international HHF trials that took place at the United States Food and Drug Administration on January 12th, 2012.
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http://dx.doi.org/10.1016/j.ahj.2014.05.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4160662PMC
August 2014

The global health and economic burden of hospitalizations for heart failure: lessons learned from hospitalized heart failure registries.

J Am Coll Cardiol 2014 Apr 5;63(12):1123-1133. Epub 2014 Feb 5.

Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, Illinois. Electronic address:

Heart failure is a global pandemic affecting an estimated 26 million people worldwide and resulting in more than 1 million hospitalizations annually in both the United States and Europe. Although the outcomes for ambulatory HF patients with a reduced ejection fraction (EF) have improved with the discovery of multiple evidence-based drug and device therapies, hospitalized heart failure (HHF) patients continue to experience unacceptably high post-discharge mortality and readmission rates that have not changed in the last 2 decades. In addition, the proportion of HHF patients classified as having a preserved EF continues to grow and may overtake HF with a reduced EF in the near future. However, the prognosis for HF with a preserved EF is similar and there are currently no available disease-modifying therapies. HHF registries have significantly improved our understanding of this clinical entity and remain an important source of data shaping both public policy and research efforts. The authors review global HHF registries to describe the patient characteristics, management, outcomes and their predictors, quality improvement initiatives, regional differences, and limitations of the available data. Moreover, based on the lessons learned, they also propose a roadmap for the design and conduct of future HHF registries.
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http://dx.doi.org/10.1016/j.jacc.2013.11.053DOI Listing
April 2014

Recognizing hospitalized heart failure as an entity and developing new therapies to improve outcomes: academics', clinicians', industry's, regulators', and payers' perspectives.

Heart Fail Clin 2013 Jul;9(3):285-90, v-vi

Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, 645 North Michigan Avenue, Chicago, IL 60611, USA.

Hospitalized heart failure (HHF) is associated with unacceptably high postdischarge mortality and rehospitalization rates. This heterogeneous group of patients, however, is still treated with standard, homogenous therapies that are not preventing their rapid deterioration. The costs associated with HHF have added demands from society, government, and payers to improve outcomes. With coordinated and committed efforts in the development of new therapies, improvements may be seen in outcomes for patients with HHF. This article summarizes concepts in developing therapies for HHF discussed during a multidisciplinary panel at the Heart Failure Society of America's Annual Scientific Meeting, September 2012.
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http://dx.doi.org/10.1016/j.hfc.2013.05.002DOI Listing
July 2013

Gender does not affect postdischarge outcomes in patients hospitalized for worsening heart failure with reduced ejection fraction (from the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan [EVEREST] Trial).

Am J Cardiol 2012 Dec 19;110(12):1803-8. Epub 2012 Sep 19.

Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Women have traditionally been underrepresented in heart failure (HF) trials, and their baseline characteristics and outcomes after hospitalization for HF are unclear. We retrospectively analyzed the clinical characteristics and outcomes of patients according to gender in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial. EVEREST randomized 4,133 patients hospitalized for HF and ejection fraction of ≤40% to tolvaptan or placebo, in addition to standard therapy. The median follow-up was 9.9 months. Log-rank tests and multivariate Cox regression models were used to compare the hazards of all-cause mortality and cardiovascular mortality or HF hospitalization. Women constituted 1,058 (26%) of the study population. The baseline characteristics were similar except that the women were older with more hypertension and diabetes and less chronic renal insufficiency, previous myocardial infarction, previous coronary revascularization, and baseline defibrillator implantation (all p <0.001). The baseline use of evidence-based HF medical therapies was similar between genders (all p >0.30). Despite a high event rate, no difference was seen in all-cause mortality (men 27% vs women 24%, multivariate hazard ratio 1.04, p = 0.61) or cardiovascular mortality plus HF hospitalization (men 42% vs women 39%, multivariate hazard ratio 1.11, p = 0.10) on univariate analysis or after adjusting for baseline covariates. In conclusion, women hospitalized for worsening HF with an ejection fraction of ≤40% were older, had more hypertension, and had received fewer procedure-based interventions than men but had relatively similar HF medication usage and clinical findings. After hospitalization for HF, women have a similarly high risk of long-term HF morbidity and mortality compared with men.
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http://dx.doi.org/10.1016/j.amjcard.2012.08.016DOI Listing
December 2012

Anticoagulation in heart failure: current status and future direction.

Heart Fail Rev 2013 Nov;18(6):797-813

Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, 645 N. Michigan Avenue, Suite 1006, Chicago, IL, 60611, USA,

Despite therapeutic advances, patients with worsening heart failure (HF) requiring hospitalization have unacceptably high post-discharge mortality and re-admission rates soon after discharge. Evidence suggests a hypercoagulable state is present in patients with HF. Although thromboembolism as a direct consequence of HF is not frequently clinically recognized, it may contribute to mortality and morbidity. Additionally, many patients with HF have concomitant disorders conferring additional thrombotic risk, including atrial fibrillation (AF) and coronary artery disease (CAD). Acute coronary syndrome (ACS), a known consequence of coronary thrombosis, is a common precipitating factor for worsening HF. Coronary thrombosis may also cause sudden death in patients with HF and CAD. Because data are largely derived from observational studies or trials of modest size, guideline recommendations on anticoagulation for HF vary between organizations. The recently presented Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial of HF patients in sinus rhythm suggested anticoagulation reduces the risk of stroke, although rates of the combined primary endpoint (death, ischemic stroke, or intracerebral hemorrhage) were similar for acetylsalicylic acid and warfarin. Newer oral anticoagulants dabigatran, apixaban, and rivaroxaban have successfully completed trials for the prevention of stroke in patients with AF and have shown benefits in the subpopulation of patients with concomitant HF. Positive results of the Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 51 (ATLAS ACS 2-TIMI 51) trial of rivaroxaban in ACS are also encouraging. These data suggest there is a need to assess the potential role for these newer agents in the management of patients hospitalized for HF who continue to have a high post-discharge event rate despite available therapies.
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http://dx.doi.org/10.1007/s10741-012-9343-xDOI Listing
November 2013

Biomarkers in acute heart failure syndromes - are they fulfilling their promise?

Cardiology 2011 11;120(1):19-21. Epub 2011 Nov 11.

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http://dx.doi.org/10.1159/000332586DOI Listing
February 2012