Impact of consensus guidelines for breast-conserving surgery in patients with ductal carcinoma in situ

BACKGROUND: Consensus guidelines published in 2016 recommended a 2 mm free margin as the standard for negative margins in patients undergoing breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). The goal of the guideline recommendation was standardization of re-excision practices. AIMS: To evaluate the impact of this consensus guideline on our institutional practices. METHODS: We identified all patients at our institution with pure DCIS who were initially treated with BCS from September 2014 to August 2018 using a prospectively-maintained institutional database. A retrospective chart review was performed to determine margin status and re-excision rates during the 2 years before and the 2 years after the guideline was published in order to determine the effect on our re-excision rates. Close margins were defined as \u3c2 mm. RESULTS: In the 2 years before the consensus guideline was published, 184 patients with DCIS underwent BCS. Twenty-six patients had positive margins and 24 underwent re-excision, including three who had completion mastectomy. Of the remaining 159 patients, 76 had ≥2 mm (negative) margins. The remaining 82 patients had close margins and 48 of these patients (58.5%) underwent re-excision, including one who had a completion mastectomy. Excluding the patients with positive margins, our re-excision rate was 30.4% prior to the guideline. In the 2 years after the consensus guideline was published, 192 patients with DCIS underwent initial BCS. Twenty-four patients had positive margins and 22 underwent re-excision, including three who had completion mastectomy. Of the remaining 168 patients, 95 patients had ≥2 mm (negative) margins. The remaining 73 patients had close margins and 45 of those patients (61.6%) underwent re-excision, including six who had completion mastectomy. Excluding the patients with positive margins, our re-excision rate was 26.8% after the guideline. CONCLUSIONS: Our institution\u27s re-excision rate did not change significantly during the 2 years before and after the publication of the consensus guideline on adequate margins for patients undergoing BCT for DCIS. Our overall re-excision rate decreased slightly. However, of the patients who had close margins, a larger proportion underwent re-excision after the guideline was published. The guideline publication appears to have affected our institutional practices slightly, but not dramatically as many of our surgeons\u27 practices were comparable to the guideline recommendations prior to 2016. We continue to use clinical judgment based on patient and tumor characteristics in deciding which patients will benefit from margin re-excision

An absence of equipoise: Examining surgeons\u27 decision talk during encounters with women considering breast cancer surgery

Shared decision-making is recommended for decisions with multiple reasonable options, yet clinicians often subtly or explicitly guide choices. Using purposive sampling, we performed a secondary analysis of 142 audio-recorded encounters between 13 surgeons and women eligible for breast-conserving surgery with radiation or mastectomy. We trained 9 surgeons in shared decision-making and provided them one of two conversation aids; 4 surgeons practiced as usual. Based on a published taxonomy of treatment recommendations (pronouncements, suggestions, proposals, offers, assertions), we examined how surgeons framed choices with patients. Many surgeons made assertions providing information and advice (usual care 71% vs. intervention 66%; p = 0.54). Some made strong pronouncements (usual care 51% vs. intervention 36%; p = .09). Few made proposals and offers, leaving the door open for deliberation (proposals usual care 21% vs. intervention 26%; p = 0.51; offers usual care 40% vs. intervention 40%; p = 0.98). Surgeons were significantly more likely to describe options as comparable when using a conversation aid, mentioning this in all intervention group encounters (usual care 64% vs. intervention 100%; p\u3c0.001). Conversation aids can facilitate offers of comparable options, but other conversational actions can inhibit aspects of shared decision-making

Lymphovascular space invasion and lack of downstaging after neoadjuvant chemotherapy are strong predictors of adverse outcome in young women with locally advanced breast cancer

Younger age diagnosis of breast cancer is a predictor of adverse outcome. Here, we evaluate prognostic factors in young women with locally advanced breast cancer (LABC). We present a retrospective review of 104 patients younger than 40 years with LABC treated with surgery, radiotherapy (RT), and chemotherapy from 2003 to 2014. Patient‐, tumor‐, and treatment‐related factors important for overall survival (OS), local/regional recurrence (LRR), distant metastasis (DM), and recurrence‐free survival (RFS) were evaluated. Mean age at diagnosis was 34 years (23–39 years) with a median follow‐up of 47 months (8–138 months). Breast‐conserving surgery was performed in 27%. Axillary lymph node dissection was performed in 85%. Sixty percent of patients received neoadjuvant chemotherapy with 19% achieving pathologic complete response (pCR), and 61% downstaged. Lymph node positivity was present in 91% and lymphovascular space invasion (LVSI) in 35%. Thirty‐two percent of patients had triple negative tumors (TN, ER‐/PR‐/HER2 nonamplified). Four‐year OS and RFS was 84% and 71%, respectively. Factors associated with worse OS on multivariate analysis include TN status, LVSI, and number of positive lymph nodes. LVSI was also associated with DM and LRR, as well as worse RFS. Downstaging was associated with improved 4 year RFS in patients receiving neoadjuvant chemotherapy (74% vs. 38%, P = 0.002). With high risks of recurrence and inferior OS compared to older women, breast cancer in young women can be difficult to treat. Among additional factors, presence of LVSI and lack of downstaging portends a particularly worse prognosis

Genesis Mission to Return Solar Wind Samples to Earth

The Genesis spacecraft, launched on 8 August 2001 from Cape Canaveral, Florida, will be the first spacecraft ever to return from interplanetary space. The fifth in NASAs line of low-cost, Discovery-class missions, its goal is to collect samples of solar wind and return them to Earth for detailed isotopic and elemental analysis. The spacecraft is to collect solar wind for over 2 years, while circling the L1 point 1.5 million km Sunward of the Earth, before heading back for a capsule-style re-entry in September 2004. After parachute deployments mid-air helicopter recovery will be used to avoid a hard landing. The mission has been in development over 10 years, and its cost, including development, mission operations, and initial sample analysis, is approximately $209 million

Characterization of an Orphan Diterpenoid Biosynthetic Operon from Salinispora arenicola

While more commonly associated with plants than microbes, diterpenoid natural products have been reported to have profound effects in marine microbe–microbe interactions. Intriguingly, the genome of the marine bacterium Salinispora arenicola CNS-205 contains a putative diterpenoid biosynthetic operon, terp1. Here recombinant expression studies are reported, indicating that this three-gene operon leads to the production of isopimara-8,15-dien-19-ol (4). Although 4 is not observed in pure cultures of S. arenicola, it is plausible that the terp1 operon is only expressed under certain physiologically relevant conditions such as in the presence of other marine organisms

Assay precision and risk of misclassification at rule-out cut-offs for high-sensitivity cardiac troponin

Clinical trials and guidelines support the use of very low high-sensitivity cardiac troponin (hs-cTn) results to rule-out a myocardial infarction (MI) ( 1) ). The International Federation of Clinical Chemistry and Laboratory Medicine Committee on Clinical Applications of Cardiac Biomarkers committee, through a modeling approach, suggests assays need to have a lower limit near 3 ng/L and an analytical variation of 10% below 7 ng/L if these low values are to perform consistently in practice ( 2) ). Our objectives for the present study were to assess: i) if any type of instrument or individual instrument could achieve a coefficient of variation (CV) of ≤10% at very low hs-cTn cut-offs (i.e., targets) recommended in clinical pathways; ii) the frequency of results at the hs-cTn target, above the target and below the target, with the latter group representing potential misclassification to the low risk group where the target level would in the intermediate risk range.<br/

Seasonality of the Meridional Overturning Circulation in the subpolar North Atlantic

Understanding the variability of the Atlantic Meridional Overturning Circulation is essential for better predictions of our changing climate. Here we present an updated time series (August 2014 to June 2020) from the Overturning in the Subpolar North Atlantic Program. The 6-year time series allows us to observe the seasonality of the subpolar overturning and meridional heat and freshwater transports. The overturning peaks in late spring and reaches a minimum in early winter, with a peak-to-trough range of 9.0 Sv. The overturning seasonal timing can be explained by winter transformation and the export of dense water, modulated by a seasonally varying Ekman transport. Furthermore, over 55% of the total meridional freshwater transport variability can be explained by its seasonality, largely owing to overturning dynamics. Our results provide the first observational analysis of seasonality in the subpolar North Atlantic overturning and highlight its important contribution to the total overturning variability observed to date

CMB-S4: Forecasting Constraints on Primordial Gravitational Waves

CMB-S4---the next-generation ground-based cosmic microwave background (CMB) experiment---is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the Universe, from the highest energies at the dawn of time through the growth of structure to the present day. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semi-analytic projection tool, targeted explicitly towards optimizing constraints on the tensor-to-scalar ratio, $r$, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2--3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments given a desired scientific goal. To form a closed-loop process, we couple this semi-analytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for $r > 0.003$ at greater than $5\sigma$, or, in the absence of a detection, of reaching an upper limit of $r < 0.001$ at $95\%$ CL.Comment: 24 pages, 8 figures, 9 tables, submitted to ApJ. arXiv admin note: text overlap with arXiv:1907.0447

CMB-S4: Forecasting Constraints on Primordial Gravitational Waves

Abstract: CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL