Resection Ratios and Tumor Eccentricity in Breast-Conserving Surgery Specimens for Surgical Accuracy Assessment.

This study aims to evaluate several defined specimen parameters that would allow to determine the surgical accuracy of breast-conserving surgeries (BCS) in a representative population of patients. These specimen parameters could be used to compare surgical accuracy when using novel technologies for intra-operative BCS guidance in the future. Different specimen parameters were determined among 100 BCS patients, including the ratio of specimen volume to tumor volume (resection ratio) with different optimal margin widths (0 mm, 1 mm, 2 mm, and 10 mm). Furthermore, the tumor eccentricity [maximum tumor-margin distance - minimum tumor-margin distance] and the relative tumor eccentricity [tumor eccentricity ÷ pathological tumor diameter] were determined. Different patient subgroups were compared using Wilcoxon rank sum tests. When using a surgical margin width of 0 mm, 1 mm, 2 mm, and 10 mm, on average, 19.16 (IQR 44.36), 9.94 (IQR 18.09), 6.06 (IQR 9.69) and 1.35 (IQR 1.78) times the ideal resection volume was excised, respectively. The median tumor eccentricity among the entire patient population was 11.29 mm (SD = 3.99) and the median relative tumor eccentricity was 0.66 (SD = 2.22). Resection ratios based on different optimal margin widths (0 mm, 1 mm, 2 mm, and 10 mm) and the (relative) tumor eccentricity could be valuable outcome measures to evaluate the surgical accuracy of novel technologies for intra-operative BCS guidance.

Angiographic patterns in spontaneous coronary artery dissection: novel diagnostic insights.

INTRODUCTION: Spontaneous coronary artery dissection (SCAD) is a rare but well-recognized cause of acute coronary syndrome, especially important in women. Invasive coronary angiography (ICA) is the fundamental diagnostic technique for the confirmation of SCAD. Knowing the angiographic patterns suggestive of SCAD is essential for the correct identification of patients with this entity. AREAS COVERED: In this narrative review, the main angiographic characteristics of SCAD lesions as detected by ICA are presented and discussed. EXPERT OPINION: In addition to the specific angiographic classification of SCAD, several authors have described complementary angiographic patterns suggestive of SCAD. Knowledge and correct identification of these angiographic patterns is essential for the correct diagnosis of patients with clinical suspicion of SCAD.

Margin assessment during breast conserving surgery using diffuse reflectance spectroscopy.

Significance: During breast-conserving surgeries, it is essential to evaluate the resection margins (edges of breast specimen) to determine whether the tumor has been removed completely. In current surgical practice, there are no methods available to aid in accurate real-time margin evaluation. Aim: In this study, we investigated the diagnostic accuracy of diffuse reflectance spectroscopy (DRS) combined with tissue classification models in discriminating tumorous tissue from healthy tissue up to 2 mm in depth on the actual resection margin of in vivo breast tissue. Approach: We collected an extensive dataset of DRS measurements on ex vivo breast tissue and in vivo breast tissue, which we used to develop different classification models for tissue classification. Next, these models were used in vivo to evaluate the performance of DRS for tissue discrimination during breast conserving surgery. We investigated which training strategy yielded optimum results for the classification model with the highest performance. Results: We achieved a Matthews correlation coefficient of 0.76, a sensitivity of 96.7% (95% CI 95.6% to 98.2%), a specificity of 90.6% (95% CI 86.3% to 97.9%) and an area under the curve of 0.98 by training the optimum model on a combination of ex vivo and in vivo DRS data. Conclusions: DRS allows real-time margin assessment with a high sensitivity and specificity during breast-conserving surgeries.

Impact of sex differences on the feasibility and safety of distal radial access for coronary procedures: a multicenter prospective observational study.

BACKGROUND: Conventional transradial access in women is associated with a lower success rate and a higher incidence of spasm compared to men. To date, the effect of sex on the performance of distal radial access (DRA) has not been fully elucidated. The aim of this study was to assess the impact of sex on catheterization success and other performance parameters of DRA procedures. METHODS: This is a prospective three-center observational study. From August 2020 to September 2022, data from all consecutive patients who underwent DRA for coronary procedures were collected. RESULTS: A total of 868 procedures were registered and stratified into two groups according to sex: women (n = 258) and men (n = 610). Female patients had less favorable baseline characteristics than male patients in terms of absent or weak pulse (29% vs. 17%; P  < 0.001), distal radial diameter (2.2 ±â€…0.3 vs. 2.4 ±â€…0.4 mm; P  < 0.001) and proximal radial diameter (2.5 ±â€…0.7 vs. 2.7 ±â€…0.7 mm; P  = 0.001). No differences in success rates were found in women compared to men (94.2% vs. 96.6%; P  = 0.135), with a higher presence of arterial spasm in women (5.8% vs. 3.0%; P  = 0.044). The preprocedural ultrasound evaluation was the only predictor of DRA success [odds ratio = 20.0 (4.739-83.333); P  < 0.001]. CONCLUSION: In patients undergoing coronary procedures, the success rate of DRA was high regardless of sex, with a higher incidence of arterial spasm in women.

Point Projection Mapping System for Tracking, Registering, Labeling, and Validating Optical Tissue Measurements.

The validation of newly developed optical tissue-sensing techniques for tumor detection during cancer surgery requires an accurate correlation with the histological results. Additionally, such an accurate correlation facilitates precise data labeling for developing high-performance machine learning tissue-classification models. In this paper, a newly developed Point Projection Mapping system will be introduced, which allows non-destructive tracking of the measurement locations on tissue specimens. Additionally, a framework for accurate registration, validation, and labeling with the histopathology results is proposed and validated on a case study. The proposed framework provides a more-robust and accurate method for the tracking and validation of optical tissue-sensing techniques, which saves time and resources compared to the available conventional techniques.

Electric control of optically-induced magnetization dynamics in a van der Waals ferromagnetic semiconductor.

Electric control of magnetization dynamics in two-dimensional (2D) magnetic materials is an essential step for the development of novel spintronic nanodevices. Electrostatic gating has been shown to greatly affect the static magnetic properties of some van der Waals magnets, but the control over their magnetization dynamics is still largely unexplored. Here we show that the optically-induced magnetization dynamics in the van der Waals ferromagnet Cr2Ge2Te6 can be effectively controlled by electrostatic gates, with a one order of magnitude change in the precession amplitude and over 10% change in the internal effective field. In contrast to the purely thermally-induced mechanisms previously reported for 2D magnets, we find that coherent opto-magnetic phenomena play a major role in the excitation of magnetization dynamics in Cr2Ge2Te6. Our work sets the first steps towards electric control over the magnetization dynamics in 2D ferromagnetic semiconductors, demonstrating their potential for applications in ultrafast opto-magnonic devices.

Non-atherosclerotic acute cardiac syndromes: spontaneous coronary artery dissection and Takotsubo syndrome. Comparison of long-term clinical outcomes.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) and Takotsubo syndrome (TTS) constitute two common causes of nonatherosclerotic acute cardiac syndrome particularly frequent in women. Currently, there is no information comparing long-term clinical outcomes in unselected patients with these conditions. METHODS: We compared the baseline characteristics, in-hospital outcomes, and the 12-month and long-term clinical outcomes of two large prospective registries on SCAD and TTS. RESULTS: A total of 289 SCAD and 150 TTS patients were included; 89% were women. TTS patients were older with a higher prevalence of cardiovascular risk factors. Precipitating triggers were more frequent in TTS patients, while emotional triggers and depressive disorders were more common in the SCAD group. Left ventricular ejection fraction was lower in TTS patients, but SCAD patients showed higher cardiac biomarkers. In-hospital events (43.3% vs. 5.2%, P <0.01) occurred more frequently in TTS patients. TTS patients also presented more frequent major adverse events at 12-month (14.7% vs. 7.1%, HR 5.3, 95% CI: 2.4-11.7, P <0.01) and long-term (median 36 vs. 31 months, P =0.41) follow-up (25.8% vs. 9.6%, HR 4.5, 95% CI: 2.5-8.2, P <0.01). Atrial fibrillation was also more frequent in TTS patients. Moreover, TTS patients presented a higher 12-month and long-term mortality (5.6% vs. 0.7%, P =0.01; and 12.6% vs. 0.7%, P <0.01) mainly driven by noncardiovascular deaths. CONCLUSION: Compared to SCAD, TTS patients are older and present more cardiovascular risk factors but less frequent depressive disorder or emotional triggers. TTS patients have a worse in-hospital, mid-term, and long-term prognosis with higher noncardiac mortality than SCAD patients.

Diffuse reflectance spectroscopy for accurate margin assessment in breast-conserving surgeries: importance of an optimal number of fibers.

During breast-conserving surgeries, it remains challenging to accomplish adequate surgical margins. We investigated different numbers of fibers for fiber-optic diffuse reflectance spectroscopy to differentiate tumorous breast tissue from healthy tissue ex vivo up to 2 mm from the margin. Using a machine-learning classification model, the optimal performance was obtained using at least three emitting fibers (Matthew's correlation coefficient (MCC) of 0.73), which was significantly higher compared to the performance of using a single-emitting fiber (MCC of 0.48). The percentage of correctly classified tumor locations varied from 75% to 100% depending on the tumor percentage, the tumor-margin distance and the number of fibers.

Primary Percutaneous Coronary Intervention in Patients With Spontaneous Coronary Artery Dissection vs Coronary Artery Disease.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a rare cause of acute myocardial infarction. Revascularization in SCAD remains very challenging and therefore is not recommended as the initial management strategy in stable SCAD without high-risk features. OBJECTIVES: The aim of this study was to compare in-hospital mortality and 30-day readmission rates between patients with SCAD with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PPCI) and patients with STEMI without SCAD undergoing PPCI. METHODS: This study was conducted using the administrative minimum dataset of the Spanish National Health System (2016-2020). Risk-standardized in-hospital mortality ratios and readmission ratios were calculated, and results were adjusted using propensity score (PS) analyses. RESULTS: A total of 65,957 episodes of PPCI were identified after exclusions. The crude in-hospital mortality rate was 4.8%. Of these, 315 (0.5%) were SCAD PPCI and 65,642 were non-SCAD PPCI. SCAD PPCI patients were younger and more frequently women than non-SCAD PPCI patients. Crude mortality (5.7% vs 4.8%), risk-standardized in-hospital mortality ratio (5.3% vs 5.3%), and PS-adjusted (315 pairs) mortality (5.7% vs 5.7%) were similar in SCAD PPCI and non-SCAD PPCI patients. In addition, crude (3% vs 3.3%) and PS-adjusted (297 pairs) 30-day readmission rates (3% vs 4%) were also similar in both groups. CONCLUSIONS: PPCI, when indicated in patients with STEMI and SCAD, has similar in-hospital mortality and 30-day readmission rates compared with PPCI for atherothrombotic STEMI. These findings support the value of PPCI in selected patients with SCAD.

Study protocol for the epigenetic characterization of angor pectoris according to the affected coronary compartment: Global and comprehensive assessment of the relationship between invasive coronary physiology and microRNAs.

BACKGROUND: MicroRNAs (miRNAs) are noncoding RNAs involved in post-transcriptional genetic regulation with a proposed role in intercellular communication. miRNAs are considered promising biomarkers in ischemic heart disease. Invasive physiological evaluation allows a precise assessment of each affected coronary compartment. Although some studies have associated the expression of circulating miRNAs with invasive physiological indexes, their global relationship with coronary compartments has not been assessed. Here, we will evaluate circulating miRNAs profiles according to the coronary pattern of the vascular compartment affectation. STUDY AND DESIGN: This is an investigator-initiated, multicentre, descriptive study to be conducted at three centres in Spain (NCT05374694). The study will include one hundred consecutive patients older than 18 years with chest pain of presumed coronary cause undergoing invasive physiological evaluation, including fractional flow reserve (FFR) and index of microvascular resistance (IMR). Patients will be initially classified into four groups, according to FFR and IMR: macrovascular and microvascular affectation (FFR≤0.80 / IMR≥25), isolated macrovascular affectation (FFR≤0.80 / IMR<25), isolated microvascular affectation (FFR>0.80 / IMR ≥25) and normal coronary indexes (FFR>0.80 / IMR<25). Patients with isolated microvascular affectation or normal indexes will also undergo the acetylcholine test and may be reclassified as a fifth group in the presence of spasm. A panel of miRNAs previously associated with molecular mechanisms linked to chronic coronary syndrome will be analysed using RT-qPCR. CONCLUSIONS: The results of this study will identify miRNA profiles associated with patterns of coronary affectation and will contribute to a better understanding of the mechanistic pathways of coronary pathology.

Prognostic implications of left ventricular systolic dysfunction in patients with spontaneous coronary artery dissection.

AIMS: Spontaneous coronary artery dissection (SCAD) is a relatively infrequent cause of acute coronary syndrome. Clinical features, angiographic findings, management, and outcomes of SCAD patients who present reduced left ventricular ejection fraction (LVEF) remain unknown. METHODS AND RESULTS: The Spanish multicentre prospective SCAD registry (NCT03607981), included 389 consecutive patients with SCAD. In 348 of these patients, LVEF could be assessed by echocardiography during the index admission. Characteristics and outcomes of patients with preserved LVEF (LVEF ≥50%, n = 295, 85%) were compared with those with reduced LVEF (LVEF <50%, n = 53, 15%). Mean age was 54 years and 90% of patients in both groups were women. The most frequent clinical presentation in patients with reduced LVEF was ST-segment elevation myocardial infarction (STEMI) (62% vs. 36%, P < 0.001), especially anterior STEMI. Proximal coronary segment and multi-segment involvement were also significantly more frequent in these patients. No differences were found on initial revascularization between groups. Patients with reduced LVEF significantly received more often neurohormonal antagonist therapy, and less frequently aspirin. In-hospital events were more frequent in these patients (13% vs. 5%, P = 0.01), with higher rates of death, cardiogenic shock, ventricular arrhythmia, and stroke. During a median follow-up of 28 months, the occurrence of a combined adverse event did not statistically differ between the two groups (19% vs. 12%, P = 0.13). However, patients with reduced LVEF had higher mortality (9% vs. 0.7%, P < 0.001) and readmission rates for heart failure (HF) (4% vs. 0.3%, P = 0.01). CONCLUSION: Patients with SCAD and reduced LVEF show differences in clinical characteristics and angiographic findings compared with SCAD patients with preserved LVEF. Although these patients receive specific medications at discharge, they had higher mortality and readmission rates for HF during follow-up.

Toward Intraoperative Margin Assessment Using a Deep Learning-Based Approach for Automatic Tumor Segmentation in Breast Lumpectomy Ultrasound Images.

There is an unmet clinical need for an accurate, rapid and reliable tool for margin assessment during breast-conserving surgeries. Ultrasound offers the potential for a rapid, reproducible, and non-invasive method to assess margins. However, it is challenged by certain drawbacks, including a low signal-to-noise ratio, artifacts, and the need for experience with the acquirement and interpretation of images. A possible solution might be computer-aided ultrasound evaluation. In this study, we have developed new ensemble approaches for automated breast tumor segmentation. The ensemble approaches to predict positive and close margins (distance from tumor to margin ≤ 2.0 mm) in the ultrasound images were based on 8 pre-trained deep neural networks. The best optimum ensemble approach for segmentation attained a median Dice score of 0.88 on our data set. Furthermore, utilizing the segmentation results we were able to achieve a sensitivity of 96% and a specificity of 76% for predicting a close margin when compared to histology results. The promising results demonstrate the capability of AI-based ultrasound imaging as an intraoperative surgical margin assessment tool during breast-conserving surgery.

Skene's Gland Cyst - Case Report of a 2-Year-Old Girl.

BACKGROUND: Skene's glands are the two largest paraurethral glands and the female homologue to the prostate glands. When their ducts become obstructed, cysts may be formed. This usually occurs in adult women. Most cases reported in pediatrics are neonatal, with a single report in a prepubertal girl. CASE REPORT: We present a 25-month-old girl with a 7 mm nontender, solid, oval, pink-orange paraurethral mass, with no change over a five-month period. Histopathology revealed the cyst to be lined with transitional epithelium consistent with a Skene's gland cyst. The child did well with no sequalae. CONCLUSION: We describe a Skene's gland cyst found in a prepubertal child.

Intracoronary thrombus assessment with cardiac computed tomography angiography in a deferred stenting strategy: the MATURE prospective study (MSCT to Assess ThrombUs REsolution).

BACKGROUND: Cardiac computed tomography angiography (CCTA) is precise in noninvasive coronary atherosclerosis characterization but its value in the diagnosis of intracoronary thrombus remains unknown. Therefore, our aim was to evaluate CCTA for intracoronary thrombus and stenosis detection in patients with acute coronary syndromes with high thrombus burden selected for a deferred stenting strategy. METHODS: We systematically performed a CCTA in consecutive patients following a deferred stenting strategy, 24 h before the scheduled repeated coronary angiography including optical coherence tomography (OCT) imaging. Intracoronary thrombus and residual stenosis were blindly and independently evaluated by both techniques. Agreement was determined per lesion using the weighted Kappa ( K ) coefficient and absolute intraclass correlation coefficient (ICC). A stratified analysis according to OCT-detected thrombus burden was also performed. RESULTS: Thirty lesions in 28 consecutive patients were analyzed. Concordance between CCTA and repeated coronary angiography in thrombus detection was good ( K = 0.554; P < 0.001), but both showed poor agreement with OCT. CCTA needed >11.5% thrombus burden on OCT to obtain adequate diagnostic accuracy. The lesions detected by angiography were more frequently classified as red thrombus (76.5 vs. 33.3%; P = 0.087) on OCT. CCTA showed an excellent concordance with coronary angiography in diameter measurement (ICC = 0.85; P < 0.001) and was able to identify all the patients with severe residual stenosis. CONCLUSIONS: Although CCTA showed just a good concordance with angiography in intracoronary thrombus detection, the agreement in residual stenosis was excellent. Thus, in patients with a high-thrombus burden selected for a deferred stenting strategy CCTA may substitute repeat angiography.

The Elongin BC Complex Negatively Regulates AXL and Marks a Differentiated Phenotype in Melanoma.

High expression of the receptor tyrosine kinase AXL is implicated in epithelial-to-mesenchymal transition, cancer progression, and therapy resistance. For example, AXL is abundant in BRAF mutant melanomas progressing on targeted BRAF/MEK inhibition. Therefore, AXL is thought to represent an attractive therapeutic target. This notwithstanding, little is known about the mechanisms governing expression of AXL. Here, we describe a FACS-based whole-genome-wide CRISPR-Cas9 screen to uncover regulators of AXL expression. We identified several genes, inactivation of which led to increased AXL expression. Most remarkable was the identification of five components that associate with the Elongin BC heterodimer. Elongin B/C engage in multiple protein-protein interactions, including the transcription factor complex subunit Elongin A, the von Hippel-Lindau (VHL) tumor suppressor protein, and members of the SOCS-box protein family. The screen identified ELOB, ELOC, SOCS5, UBE2F, and RNF7, each of which we demonstrate to serve as an inhibitor of AXL expression. Although the AXL promoter contains hypoxia response elements and Elongin B/C are found in the VHL complex, Elongin B/C unexpectedly regulate AXL independently of hypoxia. Instead, we demonstrate that the Elongin BC complex interacts with AXL through ELOB, and contributes to proteasomal AXL turnover. RNA-sequencing and IHC analyses of melanoma patient-derived xenografts and clinical samples revealed a negative association between Elongin B/C and dedifferentiation. Together, the Elongin BC complex regulates AXL and marks a differentiated melanoma phenotype. IMPLICATIONS: This study identifies the Elongin BC complex as a key regulator of AXL expression and marker of melanoma differentiation.