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Copyright of Revista Española de Cardiología (18855857) is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Dietary interventions have been proposed as therapeutic approaches for several diseases, including cancer. A low-inflammatory Mediterranean dietary intervention, conducted as a pilot study in subjects with Familial Adenomatous Polyposis (FAP), reduced markers of local and systemic inflammation. We aim to determine whether this diet may modulate faecal microRNA (miRNA) and gene expression in the gut. Changes in the faecal miRNome were evaluated by small RNA sequencing at baseline (T0), after the three-month intervention (T1), and after an additional three months (T2). Changes in the transcriptome of healthy rectal mucosa and adenomas were evaluated by RNA sequencing at T0 and T2. The identification of validated miRNA-gene interactions and functional analysis of miRNA targets were performed using in silico approaches. Twenty-seven subjects were included in this study. It was observed that the diet modulated 29 faecal miRNAs (p < 0.01; |log2 Fold Change|>1), and this modulation persisted for three months after the intervention. Levels of miR-3612-3p and miR-941 correlated with the adherence to the diet, miR-3670 and miR-4252-5p with faecal calprotectin, and miR-3670 and miR-6867 with serum calprotectin. Seventy genes were differentially expressed between adenoma and normal tissue, and most were different before the dietary intervention but reached similar levels after the diet. Functional enrichment analysis identified the proinflammatory ERK1/2, cell cycle regulation, and nutrient response pathways as commonly regulated by the modulated miRNAs and genes. Faecal miRNAs modulated by the dietary intervention target genes that participate in inflammation. Changes in levels of miRNAs and genes with oncogenic and tumour suppressor functions further support the potential cancer-preventive effect of the low-inflammatory Mediterranean diet. NCT04552405, Registered in ClinicalTrials.gov. • Low-inflammatory Mediterranean diet-induced changes in faecal miRNA levels. • The diet reduced differences in gene expression between adenoma and normal tissue. • The diet may help prevent and reduce inflammation and cancer in FAP subjects. [ABSTRACT FROM AUTHOR]

The benefit of an anterior mitral line (AML) in patients with persistent atrial fibrillation (AF) and anterior atrial scar undergoing ablation has never been investigated. The purpose of this study was to evaluate the outcomes of AML in addition to standard treatment compared to standard treatment alone (no AML) in this subset of patients. Patients with persistent AF and anterior low-voltage zone (LVZ) treated with AML in 3 centers were retrospectively enrolled. The patients were matched in 1:1 fashion with patients having persistent AF and anterior LVZ who underwent conventional ablation in the same centers. Matching parameters were age, LVZ burden, and repeated ablation. Primary endpoint was AF/atrial tachycardia (AT) recurrence. One hundred eight-six patients (age 66 ± 9 years; 34% women) were selected and divided into 2 matched groups. Bidirectional conduction block was achieved in 95% of AML. After median follow-up of 2 years, AF/AT recurrence occurred in 29% of the patients in the AML group vs 48% in the no AML group (log-rank P =.024). On Cox regression multivariate analysis, left atrial volume (hazard ratio [HR] 1.03; P =.006) and AML (HR 0.46; P =.003) were significantly associated with the primary endpoint. On univariate logistic regression, lower body mass index, older age, extensive anterior LVZ, and position of the left atrial activation breakthrough away from the AML were associated with first-pass AML block. In this retrospective matched analysis of patients with persistent AF and anterior scar, AML in addition to standard treatment was associated with improved AF/AT-free survival compared to standard treatment alone. [Display omitted] [ABSTRACT FROM AUTHOR]

Carboxytherapy involves injecting carbon dioxide in the dermal and subcutaneous layers to achieve an increase in the local microvascularization of the tissue where it is applied. Our aim is to analyze its effectiveness in the treatment of pathological scars, as well as its adverse effects. We conducted a prospective single-center study in patients under 18 years of age with atrophic and hypertrophic scars caused by surgical interventions or trauma, mainly burns. Each patient underwent two sessions, 6 weeks apart in time. Scar quality was evaluated using the Vancouver Scar Scale before the first session and 6 weeks after the second session. Adverse effects observed during the procedure and at follow-up in outpatient clinic were collected. A total of 16 patients were included (5 males; 11 females), with a median age of 12.7 years (interquartile range 8.5–15.2), in whom 25 pathologic scars were treated (14 atrophic and 11 hypertrophic). All sessions were performed under sedation, and patients were discharged the same day, without the need for hospitalization. Regarding scar quality, an improvement was observed in the median Vancouver scale score at 6 weeks after the second session (7 points) compared to the initial median score (12 points), this difference being statistically significant (p = 0.031). No serious adverse effects were observed during the procedure or during subsequent follow-up, with a median follow-up of 14 weeks. Carboxytherapy is an effective and safe minimally invasive therapy for pathologic scars, achieving a significant improvement in scar quality, with almost no contraindications. Level IV. Prospective Single-Center Case Series. • What is currently known about this topic? • Carboxytherapy has been used in recent years in the treatment of diabetic feet or aesthetic medicine (cellulite, alopecia). • What new information is contained in this article? • The use of carboxytherapy in children with pathological scars improves functional and cosmetic outcomes with scarce adverse effects. [ABSTRACT FROM AUTHOR]

Copyright of Revista Española de Cardiología (18855857) is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Despite the advances in machine learning techniques, similarity assessment among multimedia data remains a challenging task of broad interest in computer science. Substantial progress has been achieved in acquiring meaningful data representations, but how to compare them, plays a pivotal role in machine learning and retrieval tasks. Traditional pairwise measures are widely used, yet unsupervised affinity learning approaches have emerged as a valuable solution for enhancing retrieval effectiveness. These methods leverage the dataset manifold to encode contextual information, refining initial similarity/dissimilarity measures through post-processing. In other words, measuring the similarity between data objects within the context of other data objects is often more effective. This survey provides a comprehensive discussion about unsupervised post-processing methods, addressing the historical development and proposing an organization of the area, with a specific emphasis on image retrieval. A systematic review was conducted contributing to a formal understanding of the field. Additionally, an experimental study is presented to evaluate the potential of such methods in improving retrieval results, focusing on recent features extracted from Convolutional Neural Networks (CNNs) and Transformer models, in 8 distinct datasets, and over 329.877 images analyzed. State-of-the-art comparison for Flowers, Corel5k, and ALOI datasets, the Rank Flow Embedding method outperformed all state-of-art approaches, achieving 99.65%, 96.79%, and 97.73%, respectively. • Comprehensive survey on unsupervised post-processing methods for image retrieval. • Discussion including a brief history, organization, and evolution of the area. • Analysis of literature trends through keywords network analysis. • A systematic review including organization and summarization of the main works. • Experimental study involving various unsupervised methods, features, and datasets. [ABSTRACT FROM AUTHOR]

Refractory celiac disease (RCeD) is a rare complication of celiac disease (CeD) with a severe prognosis. We describe a cohort of patients with RCeD, their clinical and histological features at diagnosis, after therapy and at lymphoma onset, and the rate and causes of death over a 17-year follow-up. We retrospectively enrolled RCeD-I and RCeD-II patients attending our center between January 2002 and October 2019. Medical data were collected at diagnosis and during monitoring. Response to therapy, changes in RCeD molecular markers, number of hospitalizations, discharge diagnosis, and cause and date of death were evaluated. The control cohort consisted of 1015 responsive CeD patients. Compared with RCeD-I, RCeD-II more frequently exhibits diarrhea (83 vs 64%), anemia (61 vs 50%), hypoalbuminemia (70 vs 21%), parenteral nutrition need (48 vs 7%), ulcerative jejuno-ileitis (7 vs 39%), and extended small intestinal atrophy (62 vs 21%). One RCeD-I and six RCeD-II patients developed lymphoma. Ten RCeD-II patients died, four from lymphoma progression. Among RCeD-II patients, atrophy extension was the only parameter correlated with hypoalbuminemia and mortality. Clinical severity, response to therapy, and mortality differ between RCeD-I and RCeD-II. Atrophy extension, evaluated at capsule endoscopy, was associated with disease severity and mortality. [ABSTRACT FROM AUTHOR]

To evaluate ultrasonographic findings as a first-line imaging tool to indirectly predict the presence of parametrial endometriosis (PE) in women with suspected deep endometriosis (DE) undergoing surgery. Retrospective analysis of a prospectively collected database (ULTRA-PARAMETRENDO I study; NCT05239871). Referral center for DE. Consecutive patients undergoing laparoscopic surgery for DE. Preoperative transvaginal ultrasonography was done according to the International Deep Endometriosis Analysis consensus statement. A stepwise forward regression analysis was performed considering the simultaneous presence of DE nodules and the following ultrasonographic indirect signs of DE: diffuse adenomyosis, endometriomas, ovary fixed to the lateral pelvic wall or the uterine wall, absence of anterior/posterior sliding sign, and hydronephrosis. The gold standard for the presence of PE was surgery with histologic confirmation. Of 1079 patients, 212 had a surgical diagnosis of PE (left: 18.5%; right: 17.0%; bilateral: 15.9%). The obtained prediction model (χ2 = 222.530; p <.001) for PE included, as independent indirect DE signs presence of hydronephrosis (odds ratio [OR] = 14.5; p =.002), complete absence of posterior sliding sign (OR = 3.3; p <.001), presence of multiple endometriomas per ovary (OR = 3.0; p =.001), and ovary fixation to the uterine wall (OR = 2.4; p <.001); as independent concomitant DE nodules, presence of uterosacral nodules with the largest diameter >10 mm (OR = 3.2; p <.001), presence of rectal endometriosis with the largest diameter >25 mm (OR = 2.3; p =.004), and rectovaginal septum infiltration (OR = 2.3; p =.003). The optimal diagnostic balance was obtained considering at least 2 concomitant DE nodules and at least 1 indirect DE sign (area under the curve 0.75; 95% confidence interval, 0.72–0.79). Specific indirect ultrasonographic findings should raise suspicion of PE in women undergoing preoperative assessment for DE. The suspicion of parametrial invasion may be critical to address patients to expert leading centers, where proper diagnosis and surgical treatment for PE can be performed. [ABSTRACT FROM AUTHOR]

Prehabilitation (Prehab) programs aim to optimize patients psycho-physical condition before surgery, to improve post-operative outcomes. Although functional benefits of Prehab are known, the clinical impact does not yet have concrete evidence. The objective of this study is to evaluate the efficacy of Prehab, associated with Enhanced Recovery After Surgery (ERAS) and surgical rehabilitation (Rehab), in frail colorectal oncological patients in terms of morbidity and hospitalization. The cohort of patients undergoing Prehab between January 2020 and December 2022 (Prehab group) is compared with the historical cohort of patients operated on in the period 01/2018-12/2019, not undergoing Prehab (no-Prehab group). Prehab scheme: multimodal (physiotherapy, clinical nutrition and psychological support). All patients followed an ERAS path. Only Prehab patients followed a surgical Rehab by a dedicated nurse case-manager. Propensity score matching (PSM) and weighting (PSW) analyses were used for statistical analysis. Primary objectives: complications at 30 days and hospital stay. Secondary objectives: functional outcomes. In 3 years of preliminary enrollment, 36 patients completed the program: 22 in person, 16 in tele-prehab. The Prehab group experienced fewer complications than the no-Prehab group (PSM: 31 % vs 53 % p = 0.02; PSW: 31 % vs 51 % p = 0.02), less severe complications (CCI>20 PSM: 17 % vs 33 % p = 0.074; PSW: 17 % vs 53 % 0.026) and shorter hospital stay (4.5 vs 6 days; p = 0.02). Finally, prehabilitated patients improved their preoperative functional capacity and reduced anxiety levels. The strategy of combining Prehab with ERAS and Rehab has positively influenced post-operative clinical outcomes as well as functional parameters in our series. [ABSTRACT FROM AUTHOR]

Genetic And Morphological Evaluation (GAME) score is the newest prognostic model for patient with colorectal liver metastases (CRLMs). Pathological and radiological responses to neoadjuvant chemotherapy (NAC) are key factors for prognostic stratification of these patients. The present study aims to evaluate the GAME-score's ability to predict pathological and radiologic responses to NAC. CRLM patients who underwent liver resection after NAC from January 2010 to December 2021 were categorized by GAME scores: low risk (LR, 0–1), moderate risk (MR, 2–3), and high risk (HR, ≥4). Correlations between groups and radiological/pathological features were analyzed. Poor pathological response was defined as Tumor Regression Grade 4–5. Of 1054 liver resections for CRLMs, 448 were included. GAME scores were LR: 80 (18 %), MR: 228 (51 %), and HR: 140 (31 %). In this cohort, HR-GAME scores were associated with lower pathological response (LR: 67.1 %, MR: 74.9 %, HR: 82.6 %; p = 0.010). Radiologic progression occurred in 10 % of HR patients, significantly more than in LR (3.8 %) and MR (3.5 %) groups (p = 0.011). Multivariable analysis for independent predictors of pathological response confirmed HR-GAME (RR 1.843, p=0.025) along with age higher than 70 years (RR 2.111, p=0.022) and irinotecan-based NAC (RR 3.066, p < 0.001). For radiological progression disease after NAC, the HR-GAME score (RR 2.77, p=0.016) was the only independent predictor. HR-GAME scores were also associated with higher rates of mucinous differentiation (p = 0.021), satellitosis (p = 0.001), vascular invasion (p = 0.011), and perineural invasion (p = 0.010). GAME score category should be considered into planning of therapeutic strategy of patients with CRLMs. [ABSTRACT FROM AUTHOR]

• Geometry optimization in schematic design phases is crucial to minimize energy needs. • Annual energy needs are highly influenced by local climatic conditions. • An in-house developed aNSGA-II is used in the optimization process. • Results among 19 European cities with different latitudes and climates are analyzed. The ongoing transition towards resilient and energy-efficient cities highlights the design of new buildings as a critical concern. With the increasing urbanization in Europe and the concurrent need for energy reduction and decarbonization, it is crucial to address energy efficiency in the construction sector, as by the recently adopted European Energy Performance of Building Directive. In this context, the article focuses on the role of geometry optimization in the schematic design phase of low-energy buildings, by considering it among different European climates. Indeed, this study aims to propose a multi-objective optimization approach (using a genetic algorithm) to optimize the "genes" of the building, e.g., shape, proportions, orientation and window-to-wall ratio of residential buildings in the early design phase, to cut off a significant portion of energy consumptions. The objective is thus to minimize heating and cooling energy needs based on the best combination of the above-mentioned genes. The research investigates optimal solutions across various European climates based on the Köppen-Geiger classification, comparing the results for 19 European cities with varying climate. The findings confirm that the energy needs of buildings are strongly influenced by the climate conditions of their location. The study, which comprehends almost 250.00 different configurations, assesses, as expected, the strong effect of climate conditions on the energy needs and highlights the cross-shaped buildings as the best performing in 17 over 19 sites investigated. The optimal solution for each site leads to total energy needs that are comprised between 4.58 kWh m-2 y-1 in Porto and 19.84 kWh m-2 y-1 in Goteborg, with an average across all cities of 12.45 kWh m-2 y-1. The research provides valuable insights for professional in the construction sector, aiding them in making informed decisions during the schematic design phase to achieve low-energy buildings that are adapted to specific climates. [ABSTRACT FROM AUTHOR]

Taxanes are one of the most effective chemotherapies (CT) in breast cancer (BC), but the efficacy of taxanes rechallenge in early metastatic relapse has been poorly studied in patients previously treated by taxanes in the (neo)adjuvant setting. Our study aimed to analyse the efficacy of taxane rechallenge in case of early metastatic relapse in a multicentre retrospective observational study compared with other chemotherapies. We analysed the French national ESME metastatic BC (MBC) database and selected HER2- MBC patients who received CT in first-line treatment for a metastatic relapse occurring 3–24 months after previous (neo)adjuvant taxanes treatment. Of 23,501 female patients with MBC in ESME, 1057 met the selection criteria. 58.4% received a taxane-based regimen (75.4% concomitant bevacizumab) and 41.6% received other CT. In hormone-receptor positive (HR+)/HER2- MBC, multivariate analysis showed no difference in OS between taxanes without bevacizumab compared to other CT (HZR = 1.3 [0.97; 1.74], but taxanes was significantly associated with worse PFS (HZR = 1.48 [1.14; 1.93]). In TNBC, taxanes without bevacizumab and carboplatin/gemcitabine were not superior to other CT for OS (HZR = 1.07 [0.79; 1.44] and HZR = 0.81 [0.58; 1.13], respectively), while for PFS, taxanes was inferior (HZR = 1.33 [1.06–1.67]) and carboplatin plus gemcitabine was superior to other CT (HZR = 0.63 [0.46; 0.87]). For both subtypes, the worse outcome observed with paclitaxel was no longer observed with the addition of bevacizumab. With the limitation of retrospective design, taxanes rechallenge in early metastatic relapse of BC may result in a worse PFS in TNBC and HR+/HER2- MBC, which was not observed with the addition of bevacizumab. • Patients with HER2-advanced breast cancer (ABC) have often previously received taxanes in the (neo)adjuvant setting. • Current guidelines suggest a rechallenge by taxanes in ABC with DFI≥12 months, few data are available for DFI ≤24 months. • Taxane rechallenge in early metastatic relapse of BC (DFI ≤24 months) may result in a worse PFS in TNBC and HR+/HER2- ABC. • In TNBC, the addition of bevacizumab to taxanes improves PFS and OS for DFI ≤24 months. [ABSTRACT FROM AUTHOR]

Myocarditis is a rare extra-intestinal complication of inflammatory bowel disease (IBD), in particular, ulcerative colitis. We report a case of acute myocarditis as first manifestation of severe ulcerative colitis. A 22-year-old man was admitted with fever, bloody diarrhea, and fatigue. He had suffered from frequent bloody diarrhea, abdominal pain, fatigue, and weight loss for one month. A 12-lead-electrocardiogram showed sinus rhythm with QRS fragmentation and T waves inversion. High sensitivity troponin-I was elevated and the echocardiogram showed a mild pericardial effusion and inferior hypokinesia with normal ejection fraction. Cardiac magnetic resonance disclosed late enhancement in the inferior wall, corroborating the hypothesis of myocarditis. One week later, a colonoscopy revealed severe ulcerative extensive colitis (Mayo subscore 3). 5-aminosalicylic acid (mesalazine) and systemic steroid were started with good clinical and biochemical response. The following days the patient developed mesalazine hepatic and pancreatic induced toxicity requiring drug discontinuation and strict multi-disciplinary follow-up. At 7 months follow-up intestinal symptoms were well controlled with complete normalization of liver and pancreatic enzymes. Transthoracic echocardiography showed normal biventricular function and pericardial effusion resolution. This case underscores the importance of a high suspicion for extra intestinal involvement in patients with IBD. These complications may be multifactorial and need multidisciplinary management. • When a patient was first-time diagnosed with a severe form of inflammatory bowel disease or has a disease relapse, bear in mind myocarditis as possible extra intestinal manifestation. • Multidisciplinary management is crucial to ensure the best level of care and follow-up in a such challenging and insidious clinical picture. [ABSTRACT FROM AUTHOR]

The selection of aircraft and engine models poses a significant challenge for Low-Cost Carriers (LCCs) striving for profitability. This decision is compounded by numerous subjective and objective variables and the vast array of available aircraft and engine configurations. Current methodologies, utilizing Multi-Criteria Decision Making (MCDM) and fuzzy logic, often simplify the problem, neglecting the engine consideration and limiting variables and alternatives. In this paper, we propose a novel methodology that circumvents these simplifications, considering engine configurations within the aircraft selection and addressing this problem for 27 parameters and real 51 selection alternatives. Through the consultation of different experts in the aeronautic field, we establish a comprehensive approach to assess the relative and overall performance of multiple variables, as well as their weights and hierarchy in the selection scheme. We apply this methodology to the aircraft selection problem in the medium-haul market, providing a framework and a solution for this currently unexplored literature domain. The results provide valuable insights for validating the devised methodology and providing relevant insights on the characteristics of the medium-haul market for LCCs. • The integration of the engine consideration within the aircraft selection. • The definition of a novel framework of LCC medium-haul aircraft selection parameters. • A new method for systematically defining relative and absolute parameter performance. [ABSTRACT FROM AUTHOR]

Carbon ion therapy treatments can be monitored non-invasively with in-beam Positron Emission Tomography (PET). At CNAO the INSIDE in-beam PET scanner has been used in a clinical trial (NCT03662373) to monitor cancer treatments with proton and carbon therapy. In this work we present the analysis results of carbon therapy data, acquired during the first phase of the clinical trial, analyzing data of nine patients treated at CNAO for various malignant tumors in the head-and-neck region. The patient group contained two patients requiring replanning, and seven patients without replanning, based on established protocols. For each patient the PET images acquired along the course of treatment were compared with a reference, applying two analysis methods: the beam-eye-view (BEV) method and the γ -index analysis. Time trends in several parameters were investigated, as well as the agreement with control CTs, if available. Regarding the BEV-method, the average sigma value σ was 3.7 mm of range difference distributions for patients without changes (sensitivity of the INSIDE detector). The 3D-information obtained from the BEV analysis was partly in agreement with what was observed in the control CT. The data quality and quantity was insufficient for a definite interpretation of the time trends. We analyzed carbon therapy data acquired with the INSIDE in-beam PET detector using two analysis methods. The data allowed to evaluate sensitivity of the INSIDE detector for carbon therapy and to make several recommendations for the future. • Nine carbon therapy patients were monitored with in-beam PET (NCT03662373). • Two analysis methods were applied: gamma-index and Beam-Eye-View analysis. • The sensitivity of the INSIDE detector was evaluated for carbon therapy. • More data is needed to verify time trends in the analysis parameters and to relate them to anatomical changes. • The reliability of the 3D information should be studied in the future. [ABSTRACT FROM AUTHOR]

Adipose tissue plasticity is orchestrated by molecularly and functionally diverse cells within the stromal vascular fraction (SVF). Although several mouse and human adipose SVF cellular subpopulations have by now been identified, we still lack an understanding of the cellular and functional variability of adipose stem and progenitor cell (ASPC) populations across human fat depots. To address this, we performed single-cell and bulk RNA sequencing (RNA-seq) analyses of >30 SVF/Lin− samples across four human adipose depots, revealing two ubiquitous human ASPC (hASPC) subpopulations with distinct proliferative and adipogenic properties but also depot- and BMI-dependent proportions. Furthermore, we identified an omental-specific, high IGFBP2- expressing stromal population that transitions between mesothelial and mesenchymal cell states and inhibits hASPC adipogenesis through IGFBP2 secretion. Our analyses highlight the molecular and cellular uniqueness of different adipose niches, while our discovery of an anti-adipogenic IGFBP2+ omental-specific population provides a new rationale for the biomedically relevant, limited adipogenic capacity of omental hASPCs. [Display omitted] • A single-cell transcriptomic atlas integrating Lin− SVF cells from four different human adipose depots • In-depth transcriptional analysis of stromal populations across four human adipose depots • Adipogenic characterization of five stromal populations across three human adipose depots • Omental-specific cells characterized by high IGFBP2 expression repress adipogenesis Ferrero, Rainer, et al. perform single-cell and bulk RNA-seq of >30 samples across four human adipose depots. Different Lin− stromal cell subpopulations were transcriptionally cataloged, isolated, and functionally characterized, uncovering an omental-specific, high IGFBP2- expressing stromal population able to repress adipogenesis of adipose stem and progenitor cells via integrin receptor signaling. [ABSTRACT FROM AUTHOR]

Trastuzumab-emtansine (T-DM1), as well as lapatinib plus capecitabine were proven effective in two Phase III studies, following first-line trastuzumab plus a taxane. The introduction of dual HER2 blockade by trastuzumab and pertuzumab as first-line has positioned T-DM1 into second-line, and lapatinib plus capecitabine beyond, without formal evaluation of these strategies. ESME Data Platform (NCT03275311) included individual data from all patients aged ≥18 years, in whom first-line treatment for metastatic breast cancer (MBC) was initiated between January 1, 2008 and December 31, 2016 in one of the 18 French Comprehensive Cancer Centers. The efficacy of T-DM1 and lapatinib plus capecitabine combination, following double blockade associating trastuzumab and pertuzumab were evaluated in this national real-life database. Eligibility criteria were: female, MBC, HER2+ tumor, first-line taxane-based chemotherapy and dual HER2-blockage by trastuzumab plus pertuzumab. Cohort A received second-line T-DM1, and Cohort B second-line T-DM1 and third or fourth-line lapatinib plus capecitabine. Cohort A comprised 233 patients, and Cohort B 47 patients. Median progression-free survival (PFS) was 7.1 months in Cohort A and 4.6 months in Cohort B. Median overall survival were 36.7 months and 12.9 months, respectively. PFS was significantly dependent on the preceding treatment line's duration. In cohort A, HER2 expression status was a significant predictive factor of PFS. First-line trastuzumab plus pertuzumab do not markedly diminish T-DM1's efficacy in second-line. Similarly, sequential treatment with trastuzumab plus pertuzumab then T-DM1 does not noticeably modify the efficacy of lapatinib plus capecitabine. • French real-life cohort. • Dual blockade HER2 does not markedly diminish T-DM1's activity in second-line and lapatinib's activity in third or fourth line. • The second-line (T-DM1) PFS was significantly longer when the first-line treatment with trastuzumab plus pertuzumab was ≥12 months. [ABSTRACT FROM AUTHOR]

Intrahepatic cholangiocarcinoma is a rare disease with a poor prognosis. In patients where surgical resection is possible, outcome is influenced by perioperative morbidity and lymph node status. Laparoscopic liver resection is associated with improved clinical and oncological outcomes in primary and metastatic liver cancer compared with open liver resection, but evidence on intrahepatic cholangiocarcinoma is still insufficient. The primary aim of this study was to compare overall survival for a large series of patients treated for intrahepatic cholangiocarcinoma by open or laparoscopic approach. Secondary objectives were to compare disease-free survival, predictors of death, and recurrence. Patients treated with laparoscopic or open liver resection for intrahepatic cholangiocarcinoma from 2000 to 2018 from 3 large international databases were analyzed retrospectively. Each patient in the laparoscopic resection group (case) was matched with 1 open resection control (1:1 ratio), through a propensity score calculated on clinically relevant preoperative covariates. Overall and disease-free survival were compared between the matched groups. Predictors of mortality and recurrence were analyzed with Cox regression, and the Textbook Outcomes were described. During the study period, 855 patients met the inclusion criteria (open liver resection = 709, 82.9%; laparoscopic liver resection = 146, 17.1%). Two groups of 89 patients each were analyzed after propensity score matching, with no significant difference regarding pre- and postoperative variables. Overall survival at 1, 3, and 5 years was 92%, 75%, and 63% in the laparoscopic liver resection group versus 92%, 58%, and 49% in the open liver resection group (P =.0043). Adjusted Cox regression revealed severe postoperative complications (hazard ratio: 10.5, 95% confidence interval [1.01–109] P =.049) and steatosis (hazard ratio: 13.8, 95% confidence interval [1.23–154] P =.033) as predictors of death, and transfusion (hazard ratio: 19.2, 95% confidence interval [4.04–91.4] P <.001) and severe postoperative complications (hazard ratio: 4.07, 95% confidence interval [1.15–14.4] P =.030) as predictors of recurrence. The survival advantage of laparoscopic liver resection over open liver resection for intrahepatic cholangiocarcinoma is equivocal, given historical bias and missing data. [ABSTRACT FROM AUTHOR]

There exists a misalignment between the information given by a surgeon and the information retained by the patient. Inability to assimilate relevant information can be a factor of preoperative anxiety. The aim of this study was to assess patients' information retention according to a Fédération de Chirurgie Viscérale et Digestive (FCVD) questionnaire. From 29 June 2020 to 2 August 2020, a prospective, comparative multicenter study was conducted among 89 patients who were about to undergo digestive surgery. They were included either in a standard group (management in accordance with the usual French guidelines) or experimental group, which received a second consultation, one week before surgery. The day before being operated, all the patients filled out 3 questionnaires analyzing their percentage of retention according to two scales: the Amsterdam Preoperative Anxiety and information Scale (APAIS) and the visual analogue scale for anxiety (VAS-A). Patient comprehension of the FCVD information was 94% and 63% in the experimental and the control groups, respectively (P < 0.001). The standard group was significantly more anxious than the experimental group, with VAS-A rates of 6.2 and 4.6 (P = 0.014), respectively. On the other hand, according to the APAIS scale, they were similarly anxious, with scores of 11.3 versus 11.9, respectively (P = 0.200). A second transmission of exhaustive information shortly before digestive surgery was conducive to improved retention. Enhanced comprehension and memorization reduced preoperative anxiety. [ABSTRACT FROM AUTHOR]

Extracellular matrix (ECM) hydrogels obtained from decellularized tissues are promising biocompatible materials for tissue regeneration. These biomaterials may provide important options for endometrial pathologies such as Asherman's syndrome and endometrial atrophy, which lack effective therapies thus far. First, we performed a proteomic analysis of a decellularized endometrial porcine hydrogel (EndoECM) to describe the specific role of ECM proteins related to regenerative processes. Furthermore, we investigated the ability of a bioengineered system—EndoECM alone or supplemented with growth factors (GFs)—to repair the endometrium in a murine model of endometrial damage. For this model, the uterine horns of female C57BL/6 mice were first injected with 70% ethanol, then four days later, they were treated with: saline (negative control); biotin-labeled EndoECM; or biotin-labeled EndoECM plus platelet-derived GF, basic fibroblast GF, and insulin-like GF 1 (EndoECM+GF). Endometrial regeneration and fertility restoration were evaluated by assessing the number of glands, endometrial area, cell proliferation, neaoangiogenesis, reduction of collagen deposition, and fertility restoration. Interestingly, regenerative effects such as an increased number of endometrial glands, increased area, high cell proliferative index, development of new blood vessels, reduction of collagen deposition, and higher pregnancy rate occurred in mice treated with EndoECM+GF. Thus, a bioengineered system based on EndoECM hydrogel supplemented with GFs may be promising for the clinical treatment of endometrial conditions such as Asherman's syndrome and endometrial atrophy. In the last years, the bioengineering field has developed new and promising approaches to regenerate tissues or replace damaged and diseased tissues. Bioengineered hydrogels offer an ideal option because these materials can be used not only as treatments but also as carriers of drugs and other therapeutics. The present work demonstrates for the first time how hydrogels derived from pig endometrium loaded with growth factors could treat uterine pathologies in a mouse model of endometrial damage. These findings provide scientific evidence about bioengineered hydrogels based on tissue-specific extracellular matrix offering new options to treat human infertility from endometrial causes such as Asherman's syndrome or endometrial atrophy. [Display omitted] [ABSTRACT FROM AUTHOR]

Despite promising early results, midterm failures of the Nellix endovascular aneurysm sealing (EVAS) system (Endologix Inc, Irvine, Calif) have been reported at higher than expected rates. The management of proximal endoleaks and migration differs from those after conventional endovascular aortic aneurysm repair (EVAR) owing to the peculiar design of the Nellix device. In the present study, we report a monocentric experience in the management of EVAS complications using various techniques. We also performed a comprehensive review of the relevant literature on both open surgical and endovascular management of proximal failure of EVAS from the MEDLINE database. We retrospectively analyzed the reinterventions for type Ia endoleak and migration after elective infrarenal EVAS at our institution. We collected preoperative, intraoperative, and follow-up data. Open and endovascular techniques are described. Overall survival, aortic-related mortality, and the technical success rate (rate of exclusion of endoleaks) with endovascular techniques were the primary outcomes. We performed 101 infrarenal elective EVAS procedures from 2013 to 2018. Of the 101 patients, 20 (19.8%) had required reintervention for proximal sealing failure. The indications were type Ia (Is2, Is3) endoleak, migration >5 mm, sac expansion >5 mm, and secondary rupture. Of the 20 patients, 6 (30%) were treated with endovascular techniques—2 with a chimney Nellix-in-Nellix application and 4 with proximal relining with a covered stent. The remaining 14 patients (70%) were treated with late open conversion (OC). The average time from EVAS to reintervention was 36.1 months (range, 3-65 months). Six patients (30%) had undergone OC in an emergent setting because of secondary rupture. The technical success rate for the patients treated with endovascular reinterventions was 100%. The 30-day mortality was 20% (4 of 20), all emergent cases (four of six emergent repairs; 67%). The overall survival for the 20 patients was 75% (n = 15) at a mean follow-up of 15.1 months (range, 2-47 months). One patient had died after 7 months of non–aortic-related causes. The high reintervention rate of the Nellix graft mandates careful evaluation for its further use with the revised instructions for use, and it should not be used off-label. OC remains the strategy of choice when managing Nellix proximal sealing failures in fit patients. Chimney Nellix-in-Nellix application and transcatheter embolization are feasible alternative techniques. Proximal relining also appears to be an effective alternative to more complex interventions, although it requires further studies for validation. [ABSTRACT FROM AUTHOR]

Post-surgical recurrence of Crohn's disease (CD) after ileocolonic resection is common. Early identification of features associated with recurrence is a standard procedure of postoperative management, but the prognostic role of such features when detected at later time points is unclear. We compared the predictivity for Crohn's disease recurrence of common clinical–instrumental variables when assessed early (<12 months) or late (>36 months) after surgery. This retrospective study considered CD patients who had ileocolonic resection and were followed for a median of 7.6 years. Clinical characteristics, post-surgical therapy, endoscopy recurrence (Rutgeerts' score ≥i2) and ultrasound features were compared between subgroups who had a early or late post-surgical assessment. Univariate and multivariate analyses were done to identify variables associated with recurrence (clinical and surgical). Of 201 patients, 70 (32%) had a early and 39 (19%) had a late post-surgical assessment. The Early and Late subgroups had similar clinical characteristics. Overall, clinical relapse was observed in 131 patients (66%), surgical relapse in 31 (16%), endoscopic recurrence in 149 (75%) and ultrasonographic recurrence in 132 (66%), without significant differences in frequencies between subgroups. By Cox proportional hazard regression, endoscopic recurrence was a significant predictor of clinical recurrence overall (HR=2.31, P = 0.002) and in the Early (HR=3.85, P = 0.002) but not Late subgroup. The most informative postoperative CD assessment is the one done within the first year of surgery. Later endoscopic evaluations have no prognostic value and should be done only for clinical needs or for research purposes. [ABSTRACT FROM AUTHOR]

Preoperative biliary drainage may be essential to reduce the risk of postoperative liver failure after hepatectomy for perihilar cholangiocarcinoma. However, infectious complications related to preoperative biliary drainage may increase the risk of postoperative mortality. The strategy and optimal drainage method continues to be controversial. This is a retrospective multicenter study including patients who underwent hepatectomy for perihilar cholangiocarcinoma between 2000 and 2016 at 14 Italian referral hepatobiliary centers. The primary end point was to evaluate independent predictors for postoperative outcome in patients undergoing liver resection for perihilar cholangiocarcinoma after preoperative biliary drainage. Of the 639 enrolled patients, 441 (69.0%) underwent preoperative biliary drainage. Postoperative mortality was 8.9% (12.5% after right-side hepatectomy versus 5.7% after left-side hepatectomy; P =.003). Of the patients, 40.5% underwent preoperative biliary drainage at the first admitting hospital, before evaluation at referral centers. Use of percutaneous preoperative biliary drainage was significantly more frequent at referral centers than at community hospitals where endoscopic preoperative biliary drainage was the most frequent type. The overall failure rate after preoperative biliary drainage was 43.3%, significantly higher at community hospitals than that at referral centers (52.7% v 36.9%; P =.002). Failure of the first preoperative biliary drainage was one of the strongest predictors for postoperative complications after right-side and left-side hepatectomies and for mortality after right-side hepatectomy. Type of preoperative biliary drainage (percutaneous versus endoscopic) was not associated with significantly different risk of mortality. Failure of preoperative biliary drainage was significantly more frequent at community hospitals and it was an independent predictor for postoperative outcome. Centers' experience in preoperative biliary drainage management is crucial to reduce the risk of failure that is closely associated with postoperative morbidity and mortality. [ABSTRACT FROM AUTHOR]

• Erosive hand osteoarthritis and rheumatism are similar clinically, radiologically, and pathophysiologically. • Methotrexate at 10 mg per week is not effective for pain relief in erosive hand osteoarthritis. • Methorexate at 10 mg per week is safe in hand osteoarthritis patients over 12 months of follow-up. To examine the effect of methotrexate (MTX) on pain and structural progression in symptomatic erosive hand osteoarthritis (HOA). This 1-year prospective, single-centre, randomised, double-blind, placebo-controlled study (www.ClinicalTrial.gov , NCT01068405) followed up patients with symptomatic erosive HOA. Patients were randomised into two groups based on the drug that was administered: 10 mg methotrexate (MTX) per week or a placebo. The primary endpoint was the change in pain (determined using a visual analogue scale [VAS]) from baseline to 3 months. The secondary endpoints were pain VAS score at 12 months, clinical features (pain VAS score and function), radiographic features (the anatomical radiographic Verbruggen–Veys [VV] score and Gent University Score System), and magnetic resonance imaging (MRI) at 12 months. Sixty-four patients with HOA were randomised into either the placebo or MTX group. At 3 months, there was no significant difference in the mean decrease in the pain VAS score (mm) (MTX: 21.1 [standard deviation, 27.4], placebo: 11.7 [24.3]; p = 0.2). At 12 months, according to the VV score, erosive joints progressed significantly more to a remodelling phase in the MTX group than in the placebo group (27% vs 15%; p = 0.03). Joints with space loss appeared to be eroding less in the MTX group compared to the placebo group (8% vs 29%; p = 0.2). Synovitis on MRI at baseline could be associated with the erosive structural evolution of non-erosive joints (p = 0.02). Weekly doses of 10-mg MTX showed no superiority over the placebo in terms of pain relief at 3 or 12 months. Clinical Trial Registration Number: This study was registered at www.ClinicalTrial.gov (NCT01068405). [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: To provide information on evolution over time of leg length discrepancy in patients with syndromic and isolated lateralized overgrowth.Study Design: This retrospective study investigates leg length discrepancy longitudinally in 105 patients with lateralized overgrowth either isolated (n = 37) or associated with Beckwith-Wiedemann spectrum (n = 56) or PIK3CA-related overgrowth spectrum (n = 12). Discrepancy was measured by standard methods and categorized as minor, mild, severe, and critical, based on the thresholds of 1, 2 and 5, respectively.Results: The period of observation from diagnosis was 1.7 ± 2.6 to 9.0 ± 6.0 years. Leg length discrepancy was 11.0 ± 7.2 mm at diagnosis and 17.1 ± 14.4 mm at last visit. Both final leg length discrepancy and change over time were correlated with discrepancy at diagnosis (r2 = 0.45, P < .001 and r2 = 0.05, P = .019, respectively). Among minor leg length discrepancy at diagnosis, 47.5% remained minor, 40.0% become mild, and 12.5% severe. Among patients with discrepancy classified as severe at diagnosis, 84.6% remained severe and 15.4% evolved to critical. The isolated lateralized overgrowth group showed a milder evolution over time compared with Beckwith-Wiedemann spectrum and PIK3CA-related overgrowth spectrum groups. Among patients with Beckwith-Wiedemann, those with paternal chromosome 11 uniparental disomy had more severe leg length discrepancy at diagnosis and evolution over time.Conclusions: Leg length discrepancy associated with isolated or syndromic lateralized overgrowth tends to worsen with growth and correlates with discrepancy at first observation. Among the genotypic groups, isolated lateralized overgrowth tends to have a milder evolution, whereas Beckwith-Wiedemann spectrum predisposes to a more severe outcome, especially if associated with paternal chromosome 11 uniparental disomy genotype. [ABSTRACT FROM AUTHOR]

Preterm delivery is associated with cardiovascular remodeling and dysfunction in children and adults. However, it is unknown whether these effects are caused by the neonatal consequences of preterm birth or if these are already present in utero. We evaluated fetal cardiac morphology and function in fetuses of mothers admitted for preterm labor or preterm prelabor rupture of membranes and the association of these changes with the presence of intra-amniotic infection and/or inflammation. In this prospective cohort study, fetal echocardiography and amniocentesis were performed at admission in singleton pregnant women with preterm labor and/or preterm prelabor rupture of membranes between 24.0 and 34.0 weeks' gestation with (intra-amniotic infection and/or inflammation group, n=41) and without intra-amniotic infection and/or inflammation (non–intra-amniotic infection and/or inflammation, n=54). Controls (n=48) were outpatient pregnant women without preterm labor or preterm prelabor rupture of membranes. Intra-amniotic infection was defined by a positive amniotic fluid culture or positive 16S ribosomal RNA gene. Intra-amniotic inflammation was defined by using the amniotic fluid interleukin-6 cutoff levels previously reported by our group being >1.43 ng/mL in preterm prelabor rupture of membranes and >13.4 ng/mL in preterm labor. Fetal cardiac morphology and function was evaluated using echocardiography, and troponin-I and N-terminal pro-brain natriuretic peptide concentrations were measured in amniotic fluid from women with preterm labor or preterm prelabor rupture of membranes and compared with 20 amniotic fluid Biobank samples obtained for reasons other than preterm labor or preterm prelabor rupture of membranes or cardiac pathology. The data were adjusted for the estimated fetal weight below the 10th percentile and for preterm prelabor rupture of membranes at admission and also for gestational age at amniocentesis when amniotic fluid biomarkers were compared. From 2018 to 2021, 143 fetuses were included; 95 fetuses were from mothers admitted with a diagnosis of preterm labor or preterm prelabor rupture of membranes, and among those, 41 (28.7%) were in the intra-amniotic infection and/or inflammation group and 54 (37.8%) were in the non–intra-amniotic infection and/or inflammation group. A total of 48 (33.6%) fetuses were included in the control group. Fetuses with preterm labor and/or preterm prelabor rupture of membranes had signs of subclinical cardiac concentric hypertrophy (median left wall thickness of 0.93 [interquartile range, 0.72–1.16] in the intra-amniotic infection and/or inflammation group; 0.79 [0.66–0.92] in the non–intra-amniotic infection and/or inflammation group; and 0.69 [0.56–0.83] in controls; P <.001) and diastolic dysfunction (tricuspid A duration 0.23 seconds [0.21–0.25], 0.24 [0.22–0.25], and 0.21 [0.2–0.23]; P =.007). Systolic function was similar among groups. Higher values of amniotic fluid troponin I (1413 pg/mL [927–2334], 1190 [829–1636], and 841 [671–959]; P <.001) and N-terminal pro-brain natriuretic peptide were detected (35.0%, 17%, and 0%; P =.005) in fetuses with preterm labor or preterm prelabor rupture of membranes when compared with the control group. The highest N-terminal pro-brain natriuretic peptide concentrations were found in the intra-amniotic infection and/or inflammation group. Fetuses with preterm labor or preterm prelabor rupture of membranes showed signs of cardiac remodeling and subclinical dysfunction, which were more pronounced in those exposed to intra-amniotic infection and/or inflammation. These findings support that the cardiovascular effects observed in children and adults born preterm have, at least in part, a prenatal origin. [Display omitted] [ABSTRACT FROM AUTHOR]

• Brain-dedicated PET scanner detects Alzheimer's disease using the Centiloid scale. • The effectiveness of the Centiloid Scale requiring only PET images is demonstrated. • Centiloid Scale in a brain-dedicated PET can reduce the neurology burden on PET/CT. To evaluate whether the Centiloid Scale may be used to diagnose Alzheimer's Disease (AD) pathology effectively with the only use of amyloid PET imaging modality from a brain-dedicated PET scanner. This study included 26 patients with amyloid PET images with 3 different radiotracers. All patients were acquired both on a PET/CT and a brain-dedicated PET scanner (CareMiBrain, CMB), from which 4 different reconstructions were implemented. A new pipeline was proposed and used for the PET image analysis based on the original Centiloid Scale processing pipeline, but with only PET images. The Youden's Index was employed to calculate the optimal cutoffs for diagnosis and evaluated by the AUC, accuracy, precision, and recall metrics. The Centiloid Scale (CL) processing pipeline was validated with and without the use of MR images. The CL cutoffs for AD pathology diagnosis on the PET/CT and the 4 CMB reconstructions were 34.4 ± 2.2, 43.5 ± 3.5, 51.9 ± 12.5, 57.5 ± 6.8 and 41.8 ± 1.2 respectively. Overall, for these cutoffs all metrics obtained the maximum score. The Centiloid scale applied to PET images allows for AD pathology diagnosis. The CMB scanner can be used with the Centiloid scale to automatically assist in the diagnosis of AD pathology, relieving the large burden of neurodegenerative diseases on a traditional PET/CT. [ABSTRACT FROM AUTHOR]

Ultra-Wide-Band (UWB) technology allows for partially mitigating the NLOS and multipath effects of time-based localization in low-range applications. Thus, it has been widely proposed for indoor navigation, reaching very promising results with mature technology already available. However, an analysis of the suitability of different synchronous and asynchronous time-based architectures can provide valid conclusions for the future development of this field. For this reason, we perform in this paper a fair comparison of two traditional synchronous architectures (TOA and TDOA) and one asynchronous architecture (A-TDOA) defining the lowest error bounds for each architecture in an indoor industrial scenario devised for UAV navigation. Results have shown that although current industrial time-based localization software is mainly based on TDOA (synchronous) and Two-Way-Range (asynchronous) architectures, asynchronous localization can statistically provide more accurate and stable positioning services in indoor industrial environments. These results encourage further experimentation in other different asynchronous architectures in the coming years. [ABSTRACT FROM AUTHOR]

This paper analyzes how narcissistic CEOs behave regarding irresponsible environmental, social, and governance (ESG) strategies and whether this behavior is influenced by managerial power and the uncertainty of the environment in which the firm operates. Using a sample of Spanish firms from 2015 to 2019, the study finds that narcissistic CEOs avoid engaging in irresponsible ESG practices to safeguard their reputation and receive positive recognition from stakeholders and society. The results also suggest that the effect of CEO narcissism on ESG practices is moderated by CEO power and an uncertain environment. Narcissistic CEOs with more managerial power tend to avoid engaging in unethical ESG practices. Meanwhile, CSR committees and/or independent board directors limit the unethical ESG practices of narcissistic CEOs, confirming the relevance of both governance mechanisms in constraining ESG misconduct. [Display omitted] • CEO narcissism is negatively associated with irresponsible ESG practices. • Narcissistic CEOs reduce irresponsible ESG practices as a self-interest strategy. • By reducing irresponsible ESG practices, narcissistic CEOs improve their reputation. • Narcissistic CEOs' egos boost with power, reducing interest in irresponsible ESG practices. • Narcissistic CEOs' unethical ESG commitment decreases with CSR committee and/or independent board. [ABSTRACT FROM AUTHOR]

In-beam Positron Emission Tomography (PET) is a technique for in-vivo non-invasive treatment monitoring for proton therapy. To detect anatomical changes in patients with PET, various analysis methods exist, but their clinical interpretation is problematic. The goal of this work is to investigate whether the gamma-index analysis, widely used for dose comparisons, is an appropriate tool for comparing in-beam PET distributions. Focusing on a head-and-neck patient, we investigate whether the gamma-index map and the passing rate are sensitive to progressive anatomical changes. We simulated a treatment course of a proton therapy patient using FLUKA Monte Carlo simulations. Gradual emptying of the sinonasal cavity was modeled through a series of artificially modified CT scans. The in-beam PET activity distributions from three fields were evaluated, simulating a planar dual head geometry. We applied the 3D-gamma evaluation method to compare the PET images with a reference image without changes. Various tolerance criteria and parameters were tested, and results were compared to the CT-scans. Based on 210 MC simulations we identified appropriate parameters for the gamma-index analysis. Tolerance values of 3 mm/3% and 2 mm/2% were suited for comparison of simulated in-beam PET distributions. The gamma passing rate decreased with increasing volume change for all fields. The gamma-index analysis was found to be a useful tool for comparing simulated in-beam PET images, sensitive to sinonasal cavity emptying. Monitoring the gamma passing rate behavior over the treatment course is useful to detect anatomical changes occurring during the treatment course. • For the first time the gamma-index method was applied to simulated in-beam PET images. • A patient that gradually changed during the treatment course was considered. • The monitoring PET images were compared with a reference image without changes. • How anatomical changes are visible in the gamma-index map depends on the field. • The gamma passing rate decreased with increasing cavity emptying volume. [ABSTRACT FROM AUTHOR]

High Body mass index (BMI) is a risk factor for breast cancer among postmenopausal women and an adverse prognostic factor in early-stage. Little is known about its impact on clinical outcomes in patients with metastatic breast cancer (MBC). The National ESME-MBC observational cohort includes all consecutive patients newly diagnosed with MBC between Jan 2008 and Dec 2016 in the 18 French comprehensive cancer centers. Of 22 463 patients in ESME-MBC, 12 999 women had BMI data available at MBC diagnosis. Median BMI was 24.9 kg/m2 (range 12.1–66.5); 20% of women were obese and 5% underweight. Obesity was associated with more de novo MBC, while underweight patients had more aggressive cancer features. Median overall survival (OS) of the BMI cohort was 47.4 months (95% CI [46.2–48.5]) (median follow-up: 48.6 months). Underweight was independently associated with a worse OS (median OS 33 months; HR 1.14, 95%CI, 1.02–1.27) and first line progression-free survival (HR, 1.11; 95%CI, 1.01; 1.22), while overweight or obesity had no effect. Overweight and obesity are not associated with poorer outcomes in women with metastatic disease, while underweight appears as an independent adverse prognostic factor. • This is the first large multicenter cohort reporting BMI's effect on outcomes among patients with metastatic breast cancer. • Overweight or obese status does not negatively influence outcome of metastatic breast cancer patients, whatever the subtype. • Underweight is a strong negative independent prognostic factor on outcomes, whatever the subtype. [ABSTRACT FROM AUTHOR]

An in-depth knowledge of the geostructural characteristics of the territory is fundamental for optimizing the design of artificial structures. Feasibility, costs, duration, and issues of the works are strictly correlated with the geological, geomechanical, and in situ stress features of the area. Remotely sensed data represent a source of information for detecting tectonic structures that can be complementary to traditional surveys, with the advantage of being cheaper, of covering large areas and of reducing time for surveying. The study of the regional tectonic setting together with local structural features is fundamental to define the far-field tectonic stress and for correctly modeling the induced stress during excavation activities and monitoring stress variations. A multiscale and multidisciplinary approach was set up and applied to an area in the Alpi Apuane marble district (Tuscany, Italy). Visually and semi-automatically detected geological structures were analyzed and correlated to data from in-situ measurements in four underground marble quarries, to define the far-field stress state. This study is also an attempt to bridge the gap between structural geology analysis and remotely sensed data for far-field stress definition, correlating on-field kinematic observations and in situ stress measurements. [ABSTRACT FROM AUTHOR]

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