Abstract
The major indicators of breast cancer health disparities may include higher incidence, earlier onset, faster progression, and poorer outcomes. The ultimate goal of health disparities ...research is to elucidate actionable mechanisms of these differences to define the means of intervention that will help reduce the disparity. Breast cancer is the most common cancer and second leading cause of cancer death in American women and the new cases of invasive cancer have been increased lately in the United State. It is a heterogeneous disease with few modifiable risk factors, characterized by multiple subtypes that influence different populations with varying incidence, morbidity and mortality. Though recent genomic advances have enabled the stratification of breast cancer into numerous subtypes with differing therapeutic and prognostic values, it remains unclear why the incidence and outcome of certain breast cancers show an uneven distribution across different race/ethnic populations. For example, the higher frequency of more aggressive forms of breast cancer in young women of African descent is well known, yet why this occurs remains to be determined. To understand the mechanisms of breast cancer health disparity, we performed a molecular and genomic profiling on a unique cohort of racially diverse breast cancer patients from a catchment area in the northern part of east North Carolina and found earlier onset of breast cancer in women of African Ancestry (AA) with 32.1 % occurring before age 50 compared to 22.5 % for women of European Ancestry (EA). Furthermore, women of AA have higher levels of obesity with 35.5 % having a Body mass index (BMI) above 35 compared to 17.9 % for women of EA. Notably, women of AA also showed presence of higher stage of breast cancer with more than 26 % having stage 3 or 4 compared to 16.5 % for women of EA. We also found that women of AA showed poorer overall survival outcome from breast cancer compare to EA with Hazard Ratio of 1.67. The panel of exome sequencing of 147 tumors from this cohort revealed differential mutational frequencies in African Ancestry versus European Ancestry. The insertion/deletion mutated genes found only in African Ancestry included PAX5, CYP2A7, UGT2B17, CYP4A11, ACAA1, KIT and NAT2 with high percentage of cases with mutation account, whereas those genes unique to European Ancestry included GSTP1, PRSS53, AURKA, ATF1, BIRC2, PGAP3 and GSTA4. In addition to this, there are differentially mutated genes across specific breast cancer subtypes where ABL2, UBA1, CYP4F8, PIK3CG, CTNNA1, CYP39A1 genes are only associated with Triple Negative Breast Cancer patients. By characterizing the risk of breast cancer among ethnically diverse groups, we provide needed insights that will not only improve the development of personalized prognostic and predictive biomarkers but may also enhance breast cancer screening, treatment, survival and prevention.
Citation Format: Jung S. Byun, Tingfen Yan, Adam Sowalsky, Jack Zhu, Paul Meltzer, Nasreen Vohra, Peter Kragel, Anna Napoles, Eliseo Perez-Stable, Kevin Gardner. Characterizing breast cancer health disparities through molecular and genomic profiling of a diverse breast cancer cohort abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4246.
Abstract Aim Abdominal aortic aneurysm (AAA) is associated with chronic mural inflammation and a pro-thrombotic diathesis. It has been suggested that both may be related to biologically active ...intra-sac thrombus. The aim of this study was to examine the relationship between thrombin generation, fibrinolysis, platelet activity and AAA sac thrombus volume. Methods 30 patients (29 men) of median (IQR) age 75 (71–82) years with an infra-renal AAA > 5.5 cm in antero-posterior diameter were prospectively studied. AAA, lumen and thrombus volumes were calculated using a CT workstation (Vitrea). Plasma thrombin-antithrombin (TAT), plasminogen activator inhibitor (PAI)-1, and soluble (s) P-selectin were measured as biomarkers of coagulation, fibrinolysis and platelet activity, respectively Results Median (IQR) AAA total, lumen and thrombus volumes were 188 (147–247) cm3 , 80 (54.3-107) cm3 and 97.6 (63–127) cm3 respectively. TAT levels were significantly higher (median, QR, 7.15 4.7-31.3 μg/L, p = < 0.001) and sP-selectin levels significantly lower (median, IQR, 80.5 68–128 ng/ml, p = < 0.0001) than the normal range. PAI-1 levels (median, IQR, 20.9 8.4-50.7 ng/ml) were normal. There was no correlation between AAA thrombus volume and PAI-1 (r = − 0.25, p = 0.47), sP-Selectin (r = 0.26, p = 0.43) or TAT plasma levels (r = − 0.21, p = 0.54). Conclusion The present study confirms that patients with AAA demonstrate haemostatic derangement, but the extent of the haemostatic derangement does not correlate with AAA sac thrombus volume.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Cystatin C (Cyst C) is more sensitive marker for early renal injury. However, serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) are still used as the standard renal markers after ...endovascular aortic aneurysm repair (EVAR). The goal of this study was to compare the efficacy of Cyst C, sCr, and eGFR as markers of renal function after EVAR.
This study examined 29 patients (27 men) with a mean age of 76.9 years (range, 55-89 years) undergoing standard (n = 19) and fenestrated (n = 10) EVAR for abdominal aortic aneurysm (AAA) of mean diameter 6.9 cm (range, 5.5-10 cm). Cyst C and sCr were measured and eGFR calculated before and 1 day and 1, 6, and 12 months after EVAR.
At 24 hours after procedure, a significant increase in Cyst C (P < 0.005) and sCr (P = 0.028) and significant decrease in eGFR (P = 0.04) were seen. Cyst C continued to increase and was significantly higher at 1 (P < 0.002), 6 (P < 0.005), and 12 (P < 0.005) months compared with baseline. By contrast, sCr and eGFR did not show any significant change at 1, 6, and 12 months from the baseline level. Cyst C increased significantly postoperatively regardless of the baseline renal function. None of the patients required renal replacement therapy.
EVAR is associated with a significant increase in Cyst C starting 24 hours after the procedure and is maintained for 12 months. sCr and eGFR only show significant change at 24 hours and therefore may underestimate long-term renal damage after EVAR.
The American College of Medical Toxicology established the Toxicology Investigators Consortium (ToxIC) Case Registry in 2010. The Registry contains all medical toxicology consultations performed at ...participating sites. The Registry has continued to grow since its inception, and as of December 31, 2015, contains 43,099 cases. This is the sixth annual report of the ToxIC Registry, summarizing the additional 8115 cases entered in 2015. Cases were identified by a query of the Registry for all cases entered between January 1 and December 31, 2015. Specific data reviewed for analysis included demographics (age, race, gender), source of consultation, reason for consultation, agents and agent classes involved in exposures, signs, symptoms, clinical findings, fatalities, and treatment. By the end of 2015, there were 50 active sites, consisting of 101 separate health-care facilities; 51.2 % of cases involved females. Adults between the ages of 19 and 65 made up the majority (64.2 %) of Registry cases. Caucasian race was the most commonly reported (55.6 %); 9.6 % of cases were identified as Hispanic ethnicity. Inpatient and emergency department referrals were by far the most common referral sources (92.9 %). Intentional pharmaceutical exposures remained the most frequent reason for consultation, making up 52.3 % of cases. Of these intentional pharmaceutical exposures, 69 % represented an attempt at self-harm, and 85.6 % of these were a suicide attempt. Nonopioid analgesics, sedative-hypnotics, and antidepressant agents were the most commonly reported agent classes in 2015. Almost one-third of Registry cases involved a diagnosed toxidrome (32.8 %), with a sedative-hypnotic toxidrome being the most frequently described. Significant vital sign abnormalities were recorded in 25.3 % of cases. There were 98 fatalities reported in the Registry (1.2 %). Adverse drug reactions were reported in 4.3 % of cases. Toxicological treatment was given in 65.3 % of cases, with 33.0 % receiving specific antidotal therapy. Exposure characteristics and trends overall were similar to prior years. While treatment interventions were required in the majority of cases, fatalities were rare.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The Australian Genomics Cardiovascular Disorders Flagship was a national multidisciplinary collaboration. It aimed to investigate the feasibility of genome sequencing (GS) and functional genomics to ...resolve variants of uncertain significance (VUS) in the clinical management of patients and families with cardiomyopathies, primary arrhythmias, and congenital heart disease (CHD).
Between April 2019 and December 2021, 600 probands meeting cardiovascular disorder criteria from 17 cardiology and genetics clinics across Australia were enrolled in the Flagship and underwent GS. The Flagship adopted a tiered approach to GS analysis. Tier 1 analysis assessed genes with established clinical validity for each cardiovascular condition. Tier 2 analysis assessed lesser-evidenced research-based genes. Tier 3 analysis assessed the functional impact of VUS that remained after tier 1 and tier 2 analysis.
Overall, a pathogenic or likely pathogenic variant was identified in 41% of participants with a cardiomyopathy, 40% with an arrhythmia syndrome, and 15% with a familial CHD/CHD+Extra Cardiac Anomalies. A VUS outcome ranged from 13% for arrhythmias to 34% for CHD/CHD+Extra Cardiac Anomalies participants. Tier 2 research analysis identified a likely pathogenic/pathogenic variant for a further 15 participants and a VUS for an additional 15 participants.
The Flagship successfully facilitated a model of care that harnesses clinical GS and functional genomics for the resolution of VUS in the clinical setting. This valuable data set can be used to inform clinical practice and facilitate research into the future.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective: To assess the outcome of surgical (SR) and endovascular (ER) reconstruction for chronic mesenteric ischemia (CMI). Methods: Retrospective review of consecutive patients who underwent SR or ...ER for CMI in 3 UK vascular surgery units between 1996 and 2006. Early (<30 days; technical success, morbidity, mortality, length of hospital stay) and late (>30 days) outcomes (symptom recurrence, vessel/graft patency, reintervention, mortality) were assessed. Results: A total of 27 patients underwent 32 reconstructions (SR = 17, ER = 15). A total of 44 of 56 (79%) diseased arteries underwent SR (n = 26; bypass = 24, reimplantation = 2; occlusion = 16, stenosis = 10) or ER (n = 18; stenosis = 16, occlusion = 2). Perioperative mortality for SR and ER was 6% and 0%, respectively (P ≥ .99). Hospital stay was shorter following ER (mean, 4.3 vs. 14.2 days, P = .0003). Mean (range) follow-up for SR and ER was 34 (1-94) and 34 (0-135) months, respectively. At 2 years, SR demonstrated superior secondary patency (100% vs. 65%) and clinical patency (100% vs. 73%). Conclusions: Surgical mesenteric reconstruction is associated with significantly longer hospital stay, but superior long-term outcome compared to endovascular reconstruction.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Objective: To determine the prevalence of community‐acquired methicillin‐resistant Staphylococcus aureus (CA‐MRSA) carriage and infection among children living in an Indigenous community in ...Queensland.
Design, setting and participants: Swabs for culture of S. aureus were collected from the nose, throat and skin wounds of primary school children.
Main outcome measures: MRSA carriage, antibiotic sensitivity, genotype, and presence of the virulence factor Panton–Valentine leukocidin (PVL); and epidemiological risk factors for MRSA carriage.
Results: 92 (59%) of 157 eligible children were included in the study. Twenty‐seven (29%) carried S. aureus; 14 of these (15% of total) carried MRSA. MRSA was isolated from 29% of wound swabs, 8% of nose swabs, and 1% of throat swabs. Fourteen of 15 MRSA isolates were sensitive to all non‐β‐lactam antibiotics tested. Eight children (9%) carried CA‐MRSA clonal types: six carried the Queensland clone (ST93), and two carried the South West Pacific clone (ST30). All these isolates carried the virulence factor PVL. The remaining six children carried a hospital‐associated MRSA strain (ST5), negative for PVL.
Conclusions: We have identified a high prevalence of CA‐MRSA carriage in school children from a Queensland Indigenous community. In this setting, antibiotics with activity against CA‐MRSA should be considered for empiric therapy of suspected staphylococcal infection. Larger community‐based studies are needed to improve our understanding of the epidemiology of CA‐MRSA, and to assist in the development of therapeutic guidelines for this important infection.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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