Association of Statins and 28-Day Mortality Rates in Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

BACKGROUND: Statins may be protective in severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 infection. The aim of the current study was to evaluate the effect of in-hospital statin use on 28-day mortality rates and intensive care unit (ICU) admission among patients with SARS-CoV-2, stratified into 4 groups: those who used statins before hospitalization (treatment continued or discontinued in the hospital) and those who did not (treatment newly initiated in the hospital or never initiated). METHODS: In a cohort study of 1179 patients with SARS-CoV-2, record review was used to assess demographics, laboratory measurements, comorbid conditions, and time from admission to death, ICU admission, or discharge. Using marginal structural Cox models, we estimated hazard ratios (HRs) for death and ICU admission. RESULTS: Among 1179 patients, 676 (57%) were male, 443 (37%) were >65 years old, and 493 (46%) had a body mass index ≥30 (calculated as weight in kilograms divided by height in meters squared). Inpatient statin use reduced the hazard of death (HR, 0.566; P=.008). This association held among patients who did and those who did not use statins before hospitalization (HR, 0.270 [P=.003] and 0.493 [P=.04], respectively). Statin use was associated with improved time to death for patients aged >65 years but not for those ≤65 years old. CONCLUSION: Statin use during hospitalization for SARS-CoV-2 infection was associated with reduced 28-day mortality rates. Well-designed randomized control trials are needed to better define this relationship.

High-throughput interaction screens illuminate the role of c-di-AMP in cyanobacterial nighttime survival.

The broadly conserved signaling nucleotide cyclic di-adenosine monophosphate (c-di-AMP) is essential for viability in most bacteria where it has been studied. However, characterization of the cellular functions and metabolism of c-di-AMP has largely been confined to the class Bacilli, limiting our functional understanding of the molecule among diverse phyla. We identified the cyclase responsible for c-di-AMP synthesis and characterized the molecule's role in survival of darkness in the model photosynthetic cyanobacterium Synechococcus elongatus PCC 7942. In addition to the use of traditional genetic, biochemical, and proteomic approaches, we developed a high-throughput genetic interaction screen (IRB-Seq) to determine pathways where the signaling nucleotide is active. We found that in S. elongatus c-di-AMP is produced by an enzyme of the diadenylate cyclase family, CdaA, which was previously unexplored experimentally. A cdaA-null mutant experiences increased oxidative stress and death during the nighttime portion of day-night cycles, in which potassium transport is implicated. These findings suggest that c-di-AMP is biologically active in cyanobacteria and has non-canonical roles in the phylum including oxidative stress management and day-night survival. The pipeline and analysis tools for IRB-Seq developed for this study constitute a quantitative high-throughput approach for studying genetic interactions.

Scientific globalism during a global crisis: research collaboration and open access publications on COVID-19.

This study sought to understand the nature of scientific globalism during a global crisis, particularly COVID-19. Findings show that scientific globalism occurs differently when comparing COVID-19 publications with non-COVID-19 publications during as well as before the pandemic. Despite the tense geopolitical climate, countries increased their proportion of international collaboration and open-access publications during the pandemic. However, not all countries engaged more globally. Countries that have been more impacted by the crisis and those with relatively lower GDPs tended to participate more in scientific globalism than their counterparts.

Unique attributes of cyanobacterial metabolism revealed by improved genome-scale metabolic modeling and essential gene analysis.

The model cyanobacterium, Synechococcus elongatus PCC 7942, is a genetically tractable obligate phototroph that is being developed for the bioproduction of high-value chemicals. Genome-scale models (GEMs) have been successfully used to assess and engineer cellular metabolism; however, GEMs of phototrophic metabolism have been limited by the lack of experimental datasets for model validation and the challenges of incorporating photon uptake. Here, we develop a GEM of metabolism in S. elongatus using random barcode transposon site sequencing (RB-TnSeq) essential gene and physiological data specific to photoautotrophic metabolism. The model explicitly describes photon absorption and accounts for shading, resulting in the characteristic linear growth curve of photoautotrophs. GEM predictions of gene essentiality were compared with data obtained from recent dense-transposon mutagenesis experiments. This dataset allowed major improvements to the accuracy of the model. Furthermore, discrepancies between GEM predictions and the in vivo dataset revealed biological characteristics, such as the importance of a truncated, linear TCA pathway, low flux toward amino acid synthesis from photorespiration, and knowledge gaps within nucleotide metabolism. Coupling of strong experimental support and photoautotrophic modeling methods thus resulted in a highly accurate model of S. elongatus metabolism that highlights previously unknown areas of S. elongatus biology.

Genetic Variation in Genes Underlying Diverse Dementias May Explain a Small Proportion of Cases in the Alzheimer's Disease Sequencing Project.

BACKGROUND/AIMS: The Alzheimer's Disease Sequencing Project (ADSP) aims to identify novel genes influencing Alzheimer's disease (AD). Variants within genes known to cause dementias other than AD have previously been associated with AD risk. We describe evidence of co-segregation and associations between variants in dementia genes and clinically diagnosed AD within the ADSP. METHODS: We summarize the properties of known pathogenic variants within dementia genes, describe the co-segregation of variants annotated as "pathogenic" in ClinVar and new candidates observed in ADSP families, and test for associations between rare variants in dementia genes in the ADSP case-control study. The participants were clinically evaluated for AD, and they represent European, Caribbean Hispanic, and isolate Dutch populations. RESULTS/CONCLUSIONS: Pathogenic variants in dementia genes were predominantly rare and conserved coding changes. Pathogenic variants within ARSA, CSF1R, and GRN were observed, and candidate variants in GRN and CHMP2B were nominated in ADSP families. An independent case-control study provided evidence of an association between variants in TREM2, APOE, ARSA, CSF1R, PSEN1, and MAPT and risk of AD. Variants in genes which cause dementing disorders may influence the clinical diagnosis of AD in a small proportion of cases within the ADSP.

Chronic Mesenteric Ischemia from Diaphragmatic Compression of the Celiac and Superior Mesenteric Arteries.

Median arcuate ligament syndrome (MALS) is caused by extrinsic compression of the celiac axis leading to postprandial epigastric abdominal pain, weight loss, and vomiting. The condition is most often identified in young women, and it is a controversial, unusual cause of chronic mesenteric ischemia. Rarely, the median arcuate ligament can compress the superior mesenteric artery (SMA) in addition to the celiac artery. We present a case of MALS in a young female patient with chronic abdominal pain resulting from external compression of not only the celiac artery but also the SMA. This patient was treated with release of the median arcuate ligament via an open retroperitoneal approach in addition to limited endarterectomy and patch angioplasty of the SMA. Preoperative and postoperative 3-dimensional computed tomographic angiographic images depict the lesions and their resolution after surgery. Few other cases of MALS caused by compression of both the celiac artery and SMA have ever been described in the literature. Although rare, it is important to keep the diagnosis of MALS in mind when encountering certain patients with chronic mesenteric ischemia of unclear etiology. Updated diagnostic work-up and treatment options for this condition are described.

Late-Onset COL4A1 Mutation with Recurrent Ischemic and Hemorrhagic Strokes.

INTRODUCTION: Mutations in type IV collagen gene COL4A1 are identified as a cause of autosomal dominant cerebrovascular disease. We report an unusual late-onset presentation. CASE REPORT: A 64-year-old male was found to have an ischemic stroke and diffuse white matter changes. Genetic testing revealed COL4A1 gene mutation of heterozygous Alu insertion at intron 16. Alu elements are known as "jumping genes," and Alu insertion is not previously reported in COL4A1 genetic syndromes. Our case has attributes consistent with a heritable leukoencephalopathy: (1) late-onset presentation, (2) intracerebral hemorrhages and microbleeds, (3) bilateral symmetrical leukoencephalopathy, (4) recurrence over a short period of time, (5) bilateral retinopathy, and (6) family history notable for brain aneurysm, kidney diseases, and early-onset stroke. CONCLUSIONS: Although the majority of COL4A1 genetic syndromes featuring cerebral small vessel disease are in children, this case highlights a late-onset patient with key features of COL4A1 syndromes associated with a heterozygous Alu intronic insertion.

Black Emerging Adults With Uncontrolled Asthma: A Qualitative Study.

RATIONALE: Asthma morbidity and mortality are disproportionately high in the Black population, especially among Black emerging adults (BEAs) (age 18-30 years). Few studies have been done to identify unique challenges to asthma care in BEAs. OBJECTIVE: To assess the challenges and barriers to asthma care BEAs experience. METHODS: We conducted virtual focus groups consisting of BEAs (n = 16) with a physician diagnosis of asthma. Discussion questions regarding asthma triggers, management, and challenges were used. Focus group discussions were recorded and transcribed verbatim. The transcripts were then coded by 3 coders using a thematic saturation approach. RESULTS: Seven major domains were identified: heightened anxiety around asthma management; asthma symptoms interfering with school and/or work; asthma in social group setting; transitioning to adulthood leading to increased autonomy and financial independence; use of technology in asthma management; concerns regarding coronavirus disease 2019; and perceived discrimination and biases. These domains create complex barriers to optimal asthma management and overlapping elements were identified. Technology was described as a potential method to address these challenges. CONCLUSIONS: BEAs with asthma have unique challenges due to age and race. Physicians should address these challenges through innovative means such as technology-based interventions.

Churches as targets for cardiovascular disease prevention: comparison of genes, nutrition, exercise, wellness and spiritual growth (GoodNEWS) and Dallas County populations.

BACKGROUND: We compared cardiovascular (CV) risk factors (CVRFs) of community-based participatory research (CBPR) participants with the community population to better understand how CBPR participants relate to the population as a whole. METHODS: GoodNEWS participants in 20 African-American churches in Dallas, Texas were compared with age/sex-matched African-Americans in the Dallas Heart Study (DHS), a probability-based sample of Dallas County residents. DHS characteristics were sample-weight adjusted to represent the Dallas County population. RESULTS: Despite having more education (college education: 75 versus 51%, P< 0.0001), GoodNEWS participants were more obese (mean body mass index: 34 versus 31 kg/m(2), P< 0.001) and had more diabetes (23 versus 12%, P< 0.001) and hyperlipidemia (53 versus 14%, P< 0.001) compared with African-Americans in Dallas County. GoodNEWS participants had higher rates of treatment and control of most CVRFs (treated hyperlipidemia: 95 versus 64%, P< 0.001; controlled diabetes: 95 versus 21%, P< 0.001; controlled hypertension: 70 versus 52%, P= 0.003), were more physically active (233 versus 177 metabolic equivalent units-min/week, P< 0.0001) and less likely to smoke (10 versus 30%, P< 0.001). CONCLUSIONS: Compared with African-Americans in Dallas County, CBPR participants in church congregations were more educated, physically active and had more treatment and control of most CVRFs. Surprisingly, this motivated population had a greater obesity burden, identifying them as a prime target for CBPR-focused obesity treatment.

VMHdm/cSF-1 neuronal circuits regulate skeletal muscle PGC1-α via the sympathoadrenal drive.

OBJECTIVE: To adapt to metabolically challenging environments, the central nervous system (CNS) orchestrates metabolism of peripheral organs including skeletal muscle. The organ-communication between the CNS and skeletal muscle has been investigated, yet our understanding of the neuronal pathway from the CNS to skeletal muscle is still limited. Neurons in the dorsomedial and central parts of the ventromedial hypothalamic nucleus (VMHdm/c) expressing steroidogenic factor-1 (VMHdm/cSF-1 neurons) are key for metabolic adaptations to exercise, including increased basal metabolic rate and skeletal muscle mass in mice. However, the mechanisms by which VMHdm/cSF-1 neurons regulate skeletal muscle function remain unclear. Here, we show that VMHdm/cSF-1 neurons increase the sympathoadrenal activity and regulate skeletal muscle peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) in mice via multiple downstream nodes. METHODS: Optogenetics was used to specifically manipulate VMHdm/cSF-1 neurons combined with genetically-engineered mice and surgical manipulation of the sympathoadrenal activity. RESULTS: Optogenetic activation of VMHdm/cSF-1 neurons dramatically elevates mRNA levels of skeletal muscle Pgc-1α, which regulates a spectrum of skeletal muscle function including protein synthesis and metabolism. Mechanistically, the sympathoadrenal drive coupled with ß2 adrenergic receptor (ß2AdR) is essential for VMHdm/cSF-1 neurons-mediated increases in skeletal muscle PGC1-α. Specifically, both adrenalectomy and ß2AdR knockout block augmented skeletal muscle PGC1-α by VMHdm/cSF-1 neuronal activation. Optogenetic functional mapping reveals that downstream nodes of VMHdm/cSF-1 neurons are functionally redundant to increase circulating epinephrine and skeletal muscle PGC1-α. CONCLUSIONS: Collectively, we propose that VMHdm/cSF-1 neurons-skeletal muscle pathway, VMHdm/cSF-1 neurons→multiple downstream nodes→the adrenal gland→skeletal muscle ß2AdR, underlies augmented skeletal muscle function for metabolic adaptations.

The number of patent tibial vessels does not influence primary patency after nitinol stenting of the femoral and popliteal arteries.

OBJECTIVE: Initial TransAtlantic Inter-Society consensus (TASC) II classification has been shown to influence the patency of stented femoral and popliteal arteries. Although several studies have shown the effect of the number of runoff vessels on the durability of infrainguinal angioplasty without stenting, the influence of tibial vessel runoff on the patency of primarily stented femoral and popliteal arteries has not been as well defined. The purpose of this study was to determine whether the number of patent tibial vessels affects primary patency after primary stenting of the femoral and popliteal arteries. METHODS: The records of all patients undergoing angioplasty and primary nitinol stenting of the femoral and popliteal arteries, by or under the supervision of one vascular surgeon, were reviewed. Results were analyzed by both the number of patent tibial vessels documented on periprocedural angiography and by using a modified Society for Vascular Surgery runoff score. TASC II classification was also recorded. Kaplan-Meier survival curves were plotted and differences between groups tested by log-rank method. Fisher exact and χ(2) tests were used to compare categoric factors. RESULTS: During a 7-year period, 289 limbs in 236 patients underwent primary stenting of the femoral and popliteal arteries. Overall primary patency was 70.3% at 12 months, 52.4% at 24 months, and 39.1% at 36 months. Limbs classified as TASC A or B had significantly better patency rates than those classified as TASC C or D (P < .001). While the number of runoff vessels decreased with worsening of the TASC classification (P = .024), overall (P = .355), and within individual TASC classes (P ≥ .092 for each), there was no difference in the primary patency of stented segments with good runoff and those with compromised runoff. Limbs with poor runoff (one or no vessels) were no more likely to fail with occlusion than their counterparts with two or three patent tibial vessels (P = .383). The number of patent tibial vessels at the time of initial stenting did not impact ultimate limb salvage (P = .063). CONCLUSIONS: The number of patent tibial vessels does not influence the primary patency of primarily stented femoral and popliteal arteries. TASC II classification appears to be significantly more predictive of initial failure after angioplasty and stenting of these vessels.

Anthropometric measures, presence of metabolic syndrome, and adherence to physical activity guidelines among African American church members, Dallas, Texas, 2008.

INTRODUCTION: The low prevalence of physical activity among African Americans and high risk of cardiovascular disease lends urgency to assessing the association between metabolic syndrome, abdominal obesity, and adherence to current physical activity guidelines. Few studies have examined this association among African American adults. METHODS: We examined the association between demographic characteristics, anthropometric measures, and metabolic syndrome and adherence to the 2008 Department of Health and Human Services guidelines for moderate and vigorous physical activity. Participants were 392 African American church members from congregations in Dallas, Texas. Physical activity levels were assessed via a validated questionnaire (7-Day Physical Activity Recall), and metabolic syndrome was determined on the basis of the American Heart Association/National Heart, Lung, and Blood Institute diagnostic criteria. We used bivariate and multinomial logistic regression to examine the associations. RESULTS: Meeting guidelines for vigorous physical activity was significantly and independently associated with the absence of metabolic syndrome among women (odds ratio, 4.71; 95% confidence interval, 1.63-13.14; P = .003), after adjusting for covariates. No association was found between meeting moderate or vigorous physical activity guidelines and metabolic syndrome among men. Meeting physical activity guidelines was not associated with body mass index or waist circumference among this sample of predominantly overweight and obese African American church members. CONCLUSION: Results indicate that meeting the 2008 guidelines for vigorous physical activity is associated with the absence of metabolic syndrome among African American women. This finding might suggest the need to integrate vigorous physical activity into interventions for African American women as a preventive therapy for cardiovascular risk. 

Statins Are Associated with Improved 28-day Mortality in Patients Hospitalized with SARS-CoV-2 Infection.

BACKGROUND: Statins may be protective in viral infection and have been proposed as treatment in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. OBJECTIVE: We evaluated the effect of statins on mortality in four groups hospitalized with (SARS-CoV-2) infection (continued statin, newly initiated statin, discontinued statin, never on statin). DESIGN: In a single center cohort study of 1179 patients hospitalized with SARS-CoV-2 infection, the outcome of death, Intensive Care Unit (ICU) admission or hospital discharge was evaluated. Patients' statin use, laboratory data, and co-morbidities were determined via chart review and electronic health records. Using marginal structural models to account for timing of statin initiation and competing risks, we compared the likelihood of severe outcomes in the four statin exposure groups. SETTING: Academic medical center in the United States. PARTICIPANTS: Patients hospitalized with SARS-CoV-2 infection. MEASUREMENTS: 28-day mortality, ICU admission, or discharge. RESULTS: Among 1179 patients, 360 were never on a statin, 311 were newly initiated on a statin, 466 were continued on a statin, and 42 had a statin discontinued. In this cohort, 154 (13.1%) patients died by 28-days. With marginal structural model analysis, statin use reduced the hazard of 28-day mortality (HR 0.566 [CI 0.372, 0.862], p = 0.008). Both new initiation of statins (HR 0.493 [CI 0.253, 0.963], p=0.038) and continuing statin therapy reduced the hazard of 28-day mortality (HR 0.270 [CI 0.114, 0.637], p=0.003). Sensitivity analysis found that statin use was associated with improved mortality for patients > 65 years, but not for patients 65 years or younger. LIMITATION: Observational design. CONCLUSION: Statin therapy during hospitalization for SARS-CoV-2 infection, including new initiation and continuation of therapy, was associated with reduced short-term mortality.

The efficacy of blood culture in postoperative patients.

Blood cultures are often obtained in postoperative patients to rule out bloodstream infections. Our study objectives were to determine the efficacy of blood cultures in postoperative patients with suspected sepsis and to determine variables predisposing patients to positive cultures. This was a retrospective study including patients with blood cultures drawn from January to March 2009 at our institution. We recorded demographics, presence of fever (temperature 101.5 degrees F or higher), elevated white blood cell count (12,000/microL or greater), central line, diabetes, intensive care unit admission, postoperative day of blood draw, National Research Council surgical wound classification, and pre- or postoperative antibiotics. Blood cultures were drawn from 150 patients undergoing surgery within 30 days prior. Sixteen had positive cultures and nine were true-positives (6.3%). There was no statistical difference (P > 0.05) between patients with positive and negative cultures except that those with negative cultures were more likely to have received preoperative antibiotics (P = 0.0186). Blood cultures are invasive, expensive tests with low yield. We recommend that blood cultures be drawn in patients not receiving preoperative antibiotics who have undergone surgery more than 4 days before culture.

Intramuscular stimulation vs sham needling for the treatment of chronic midportion Achilles tendinopathy: A randomized controlled clinical trial.

BACKGROUND: The insertion of filiform needles intramuscularly (a.k.a. intramuscular stimulation/dry needling) has been suggested as a possible treatment for various painful musculoskeletal conditions. Our aim was to answer the question, is intramuscular stimulation more effective than sham intramuscular stimulation/dry needling for the treatment of Achilles tendinopathy? METHODS: 52 participants with persistent midportion Achilles tendinopathy began and 46 completed one of three treatment protocols which were randomly assigned: (G3) a 12-week rehabilitation program of progressive tendon loading plus intramuscular stimulation (n = 25), (G2) the same rehabilitation program but with sham intramuscular stimulation (n = 19), or (G1) a reference group of rehabilitation program alone (as an additional control) (n = 8). The a priori primary outcome measure was change in VISA-A score at 12 weeks-VISA-A was also measured at 6 weeks, and at 6 and 12 months. Secondary outcome measures include the proportion of patients who rated themselves as much or very much improved (%), dorsiflexion range of motion (degrees), and tendon thickness (mm). RESULTS: The study retention was 94% at 12 weeks and 88% at 1 year. VISA-A score improved in all three groups over time (p<0.0001), with no significant difference among the three groups in VISA-A score at the start of the study (mean ± SD: G3 59 ± 13, G2 57 ± 17, G1 56 ± 22), at 12 weeks (G3 76 ± 14, G2 76 ± 15, G1 82 ± 11) or at any other timepoint. The percentage of patients who rated themselves as much or very much improved (i.e. treatment success) was not different after 12 weeks (G3 70%, G2 89%, G1 86% p = 0.94), or at 26 (p = 0.62) or 52 weeks (p = 0.71). No clinically significant effects of intervention group were observed in any of the secondary outcome measures. CONCLUSION: The addition of intramuscular stimulation to standard rehabilitation for Achilles tendinopathy did not result in any improvement over the expected clinical benefit achieved with exercise-based rehabilitation alone.

Is wide local excision for pilonidal disease still justified?

There is an ongoing debate regarding the optimal operation for chronic pilonidal disease. The current study analyzes the outcome of wide local excision (WLE) compared with unroofing and marsupialization (UM) as primary intervention for chronic pilonidal disease. A retrospective review of a single institution experience over a 5-year period was performed. Sixty-eight patients were treated for pilonidal disease. Their mean age was 25 years. There were 42 males (62%) and 26 females (38%). Twenty-six patients underwent WLE and 42 had UM. The type of operation was based on surgeon preference, but individual surgeons were consistent with their choice. Mean time for final healing was significantly higher for WLE compared with UM (21 vs. 6 weeks, P < 0.01). Postoperative complications and reoperative rate were significantly higher in the WLE group (P < 0.01). Nine patients in the WLE group (35%) required one or more reoperations compared with only one (2%) in the UM group (P < 0.01). This study demonstrates that WLE carries a high complication and reoperative rate. UM should be considered as the initial operation for most patients with pilonidal disease.

The cardiovascular health of urban African Americans: diet-related results from the Genes, Nutrition, Exercise, Wellness, and Spiritual Growth (GoodNEWS) trial.

African Americans have a higher incidence of cardiovascular disease (CVD) than Americans in general and are thus prime targets for efforts to reduce CVD risk. Dietary intake data were obtained from African Americans participating in the Genes, Nutrition, Exercise, Wellness, and Spiritual Growth (GoodNEWS) Trial. The 286 women and 75 men who participated had a mean age of 49 years; 53% had hypertension, 65% had dyslipidemia, and 51% met criteria for metabolic syndrome. Their dietary intakes were compared with American Heart Association and National Heart, Lung, and Blood Institute nutrition parameters to identify areas for improvement to reduce CVD risk in this group of urban church members in Dallas, TX. Results from administration of the Dietary History Questionnaire indicated median daily intakes of 33.6% of energy from total fat, 10.3% of energy from saturated fat, 171 mg cholesterol, 16.3 g dietary fiber, and 2,453 mg sodium. A beneficial median intake of 2.9 cups fruits and vegetables per day was coupled with only 2.7 oz fish/week and an excessive intake of 13 tsp added sugar/day. These data indicate several changes needed to bring the diets of these individuals--and likely many other urban African Americans--in line with national recommendations, including reduction of saturated fat, sodium, and sugar intake, in addition to increased intake of fatty fish and whole grains. The frequent inclusion of vegetables should be encouraged in ways that promote achievement of recommended intakes of energy, fat, fiber, and sodium.

Is the Oncotype DX assay necessary in strongly estrogen receptor-positive breast cancers?

The 21-gene Oncotype DX recurrence score (RS) assay quantifies risk of distant recurrence and predicts benefit from chemotherapy in tamoxifen-treated estrogen receptor (ER)-positive, node-negative breast cancer. Although clinically useful, the assay costs roughly $4650. Because the assay is weighted heavily towards expression of ER, our objective was to determine its clinical utility in strongly ER-positive tumors. This was a retrospective study of Huntington Hospital patients undergoing an Oncotype DX assay between 2007 and 2010. Data collected included patient age, expression of ER, progesterone receptor (PR), HER2/neu, ki67, and p53, tumor size, node status, lymphovascular invasion, and nuclear grade. Of 133 total patients, 84 (63.2%) had strongly ER-positive tumors (≥90% expression). Only seven of 84 patients (8.3%) had a high risk RS (>30), indicating statistically significant predicted benefit from chemotherapy. All seven had intermediate to high ki67 expression (>20%) and lower PR expression (≤50%). Our study demonstrates that the clinical utility of the Oncotype DX assay in these patients is limited as most patients with strongly ER-positive tumors will have a low or intermediate RS. Future studies are needed to identify additional predictive factors in these patients with otherwise good prognosis.