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Abstract Background The role of computed tomography (CT) in the diagnosis and characterization of coronavirus disease 2019 (COVID-19) pneumonia has been widely recognized. We evaluated the performance of a software for quantitative analysis of chest CT, the LungQuant system, by comparing its results with independent visual evaluations by a group of 14 clinical experts. The aim of this work is to evaluate the ability of the automated tool to extract quantitative information from lung CT, relevant for the design of a diagnosis support model. Methods LungQuant segments both the lungs and lesions associated with COVID-19 pneumonia (ground-glass opacities and consolidations) and computes derived quantities corresponding to qualitative characteristics used to clinically assess COVID-19 lesions. The comparison was carried out on 120 publicly available CT scans of patients affected by COVID-19 pneumonia. Scans were scored for four qualitative metrics: percentage of lung involvement, type of lesion, and two disease distribution scores. We evaluated the agreement between the LungQuant output and the visual assessments through receiver operating characteristics area under the curve (AUC) analysis and by fitting a nonlinear regression model. Results Despite the rather large heterogeneity in the qualitative labels assigned by the clinical experts for each metric, we found good agreement on the metrics compared to the LungQuant output. The AUC values obtained for the four qualitative metrics were 0.98, 0.85, 0.90, and 0.81. Conclusions Visual clinical evaluation could be complemented and supported by computer-aided quantification, whose values match the average evaluation of several independent clinical experts. Key points We conducted a multicenter evaluation of the deep learning-based LungQuant automated software. We translated qualitative assessments into quantifiable metrics to characterize coronavirus disease 2019 (COVID-19) pneumonia lesions. Comparing the software output to the clinical evaluations, results were satisfactory despite heterogeneity of the clinical evaluations. An automatic quantification tool may contribute to improve the clinical workflow of COVID-19 pneumonia.

Abstract Background Cancers of the Vater ampulla (ampullary cancers, ACs) account for less than 1% of all gastrointestinal tumors. ACs are usually diagnosed at advanced stage, with poor prognosis and limited therapeutic options. BRCA2 mutations are identified in up to 14% of ACs and, differently from other tumor types, therapeutic implications remain to be defined. Here, we report a clinical case of a metastatic AC patient in which the identification of a BRCA2 germline mutation drove a personalized multimodal approach with curative-intent. Case presentation A 42-year-old woman diagnosed with stage IV BRCA2 germline mutant AC underwent platinum-based first line treatment achieving major tumor response but also life-threatening toxicity. Based on this, as well as on molecular findings and expected low impact of available systemic treatment options, the patient underwent radical complete surgical resection of both primary tumor and metastatic lesions. Following an isolated retroperitoneal nodal recurrence, given the expected enhanced sensitivity to radiotherapy in BRCA2 mutant cancers, the patient underwent imaging-guided radiotherapy leading to long-lasting complete tumor remission. After more than 2 years, the disease remains radiologically and biochemically undetectable. The patient accessed a dedicated screening program for BRCA2 germline mutation carriers and underwent prophylactic bilateral oophorectomy. Conclusions Even considering the intrinsic limitations of a single clinical report, we suggest that the finding of BRCA germline mutations in ACs should be taken into consideration, together with other clinical variables, given their potential association with remarkable response to cytotoxic chemotherapy that might be burdened with enhanced toxicity. Accordingly, BRCA1/2 mutations might offer the opportunity of personalizing treatment beyond PARP inhibitors up to the choice of a multimodal approach with curative-intent.

The design of structures submitted to aerodynamic loads usually requires the development of specific computational models considering fluid-structure interactions. Models using structural frame elements are developed in several relevant applications such as, the design of advanced aircraft wings, wind turbine blades or power transmission lines. In the case of flexible frame structures submitted to fluid flows, the computation of inertial and aerodynamic forces for large displacements and rotations is a challenging task. In this article, we present a novel formulation for the efficient computation of aerodynamic forces in frame structures, coupling the co-rotational framework with the quasi-steady theory. A numerical procedure is provided considering a tangent matrix for the aerodynamic forces. This formulation is implemented in the open-source library ONSAS, allowing users to reproduce the results or solve other frame nonlinear dynamic problems. The proposed formulation and its implementation are validated through the resolution of four numerical examples. The formulation and the numerical procedure proposed efficiently provide accurate solutions for these challenging problems with large displacements and rotations.

Abstract Background To develop a pipeline for automatic extraction of quantitative metrics and radiomic features from lung computed tomography (CT) and develop artificial intelligence (AI) models supporting differential diagnosis between coronavirus disease 2019 (COVID-19) and other viral pneumonia (non-COVID-19). Methods Chest CT of 1,031 patients (811 for model building; 220 as independent validation set (IVS) with positive swab for severe acute respiratory syndrome coronavirus-2 (647 COVID-19) or other respiratory viruses (384 non-COVID-19) were segmented automatically. A Gaussian model, based on the HU histogram distribution describing well-aerated and ill portions, was optimised to calculate quantitative metrics (QM, n = 20) in both lungs (2L) and four geometrical subdivisions (GS) (upper front, lower front, upper dorsal, lower dorsal; n = 80). Radiomic features (RF) of first (RF1, n = 18) and second (RF2, n = 120) order were extracted from 2L using PyRadiomics tool. Extracted metrics were used to develop four multilayer-perceptron classifiers, built with different combinations of QM and RF: Model1 (RF1-2L); Model2 (QM-2L, QM-GS); Model3 (RF1-2L, RF2-2L); Model4 (RF1-2L, QM-2L, GS-2L, RF2-2L). Results The classifiers showed accuracy from 0.71 to 0.80 and area under the receiving operating characteristic curve (AUC) from 0.77 to 0.87 in differentiating COVID-19 versus non-COVID-19 pneumonia. Best results were associated with Model3 (AUC 0.867 ± 0.008) and Model4 (AUC 0.870 ± 0.011. For the IVS, the AUC values were 0.834 ± 0.008 for Model3 and 0.828 ± 0.011 for Model4. Conclusions Four AI-based models for classifying patients as COVID-19 or non-COVID-19 viral pneumonia showed good diagnostic performances that could support clinical decisions.

Growing evidence suggests that artificial intelligence tools could help radiologists in differentiating COVID-19 pneumonia from other types of viral (non-COVID-19) pneumonia. To test this hypothesis, an R-AI classifier capable of discriminating between COVID-19 and non-COVID-19 pneumonia was developed using CT chest scans of 1031 patients with positive swab for SARS-CoV-2 (n = 647) and other respiratory viruses (n = 384). The model was trained with 811 CT scans, while 220 CT scans (n = 151 COVID-19; n = 69 non-COVID-19) were used for independent validation. Four readers were enrolled to blindly evaluate the validation dataset using the CO-RADS score. A pandemic-like high suspicion scenario (CO-RADS 3 considered as COVID-19) and a low suspicion scenario (CO-RADS 3 considered as non-COVID-19) were simulated. Inter-reader agreement and performance metrics were calculated for human readers and R-AI classifier. The readers showed good agreement in assigning CO-RADS score (Gwet’s AC2 = 0.71, p < 0.001). Considering human performance, accuracy = 78% and accuracy = 74% were obtained in the high and low suspicion scenarios, respectively, while the AI classifier achieved accuracy = 79% in distinguishing COVID-19 from non-COVID-19 pneumonia on the independent validation dataset. The R-AI classifier performance was equivalent or superior to human readers in all comparisons. Therefore, a R-AI classifier may support human readers in the difficult task of distinguishing COVID-19 from other types of viral pneumonia on CT imaging.

Background: Disability related to incurable cancer affects over a million Europeans each year and people with cancer rank loss of function among the most common unmet supportive care needs. Objectives: To test the clinical and cost-effectiveness of an integrated short-term palliative rehabilitation intervention, to optimise function and quality of life in people affected by incurable cancer. Design: This is a multinational, parallel group, randomised, controlled, assessor blind, superiority trial. Methods: The INSPIRE consortium brings together leaders in palliative care, oncology and rehabilitation from partner organisations across Europe, with complementary expertise in health service research, trials of complex interventions, mixed-method evaluations, statistics and economics. Partnership with leading European civil society organisations ensures citizen engagement and dissemination at the highest level. We will conduct a multinational randomised controlled trial across five European countries, recruiting participants to assess the effectiveness of palliative rehabilitation for people with incurable cancer on the primary outcome – quality of life – and secondary outcomes including disability, symptom burden and goal attainment. To support trial conduct and enhance analysis of trial data, we will also conduct: comparative analysis of current integration of rehabilitation across oncology and palliative care services; mixed-method evaluations of equity and inclusivity, processes and implementation for the intervention, at patient, health service and health system levels. Finally, we will conduct an evidence synthesis, incorporating INSPIRE findings, and a Delphi consensus to develop an international framework for palliative rehabilitation practice and policy, incorporating indicators, core interventions, outcomes and integration methods. Scientific contribution: If positive, the trial could produce a scalable and equitable intervention to improve function and quality of life in people with incurable cancer and reduce the burden of care for their families. It could also upskill the practitioners involved and motivate future research questions. The intervention could be adapted and integrated into different health systems using existing staff and services, with little or no additional cost.

Background: Retzius-sparing (RS) robot-assisted radical prostatectomy represents a valid surgical treatment option for prostate cancer (PCa) patients. However, the available evidence on the role of RS in high-risk (HR) PCa setting is sparse. Objective: To describe our RS technique for HR-PCa patients and to evaluate intra-, peri-, and postoperative oncological and functional outcomes. Design, setting, and participants: A total of 340 D’Amico HR-PCa patients underwent RS at a single high-volume centre between 2011 and 2020. Surgical procedure: Surgical procedures were performed by five experienced robotic surgeons. Measurements: Complications were collected according to the standardised methodology proposed by the European Association of Urology guidelines. Postoperative outcomes were evaluated in patients with complete follow-up data (n = 320). Biochemical recurrence (BCR) was defined as two consecutive prostate-specific antigen values of ≥0.2 ng/ml. Urinary continence (UC) recovery was defined as the use of zero or one safety pad. Kaplan-Meier and multivariable logistic and Cox regression models were performed. Results and limitations: Fourteen patients (4%) experienced intraoperative complications and 52 90-d complications occurred in 44 patients (14%), of whom 24 had Clavien-Dindo 3a/b. Final pathology reported 49% International Society of Urological Pathology (ISUP) grade 4–5, 55% ≥pT3a, and 28.8% positive surgical margins (PSMs; 9.4% focal and 19.4% extended PSMs). The median follow-up was 47 mo. Overall, 35.3% and 1.3% harboured BCR and died from PCa. At 4 yr of follow-up, BCR-free survival and additional treatment-free survival were 63.6% and 56.6%, respectively. ISUP 4–5 at biopsy (odds ratio [OR]: 2.6), prostate volume (OR: 1.03), partial or full nerve sparing (OR: 1.9), and full bladder neck preservation (OR: 2.2) were independent predictors of PSMs. Pathological ISUP 4–5 (hazard ratio [HR]: 1.5) and PSMs (HR: 2.3) were independent predictors of BCR. Pathological ISUP 4–5 (HR: 1.5), PSMs (HR: 2.4), pT ≥3b (HR: 1.8), and pN ≥1 (HR: 1.8) were independent predictors of additional treatment. Immediate UC recovery was recorded in 53% patients. The 1- and 2-yr UC recovery and erectile function recovery were, respectively, 84% and 85%, and 43% and 50%. Conclusions: RS in HR-PCa patients allows optimal intra-, peri-, and postoperative outcomes. The RS approach should be considered a valid surgical treatment option for HR-PCa patients in expert hands. Patient summary: Relying on the largest cohort of high-risk prostate cancer patients treated with Retzius sparing (RS), we observed that the RS approach is safe and allows optimal cancer control, without significantly compromising functional outcomes.

Abstract Background To evaluate the potential benefits of the Magnetic Resonance-guided high intensity Focused Ultrasound (MRgFUS) introduction in the clinical practice, for the treatment of uterine fibroids, in comparison with the standard “conservative” procedures, devoted to women who wish to preserve their uterus or enhance fertility: myomectomy and uterine artery embolization (UAE). Methods A Health Technology Assessment was conducted, assuming the payer’s perspective (Italian National Healthcare Service). The nine EUnetHTA Core Model dimensions were deeply investigated, by means of i) a literature review; ii) the implementation of health economics tools (useful for uterine fibroids patients’ clinical pathway economic evaluation, and budget impact analysis), to define MRgFUS economic and organizational sustainability, and iii) administration of specific questionnaires filled by uterine fibroids’ experts, to gather their perceptions on the three possible conservative approaches (MRgFUS, UAE and myomectomy). Results Literature revealed that MRgFUS would generate several benefits, from a safety and an efficacy profile, with significant improvement in symptoms relief. Advantages emerged concerning the patients’ perspective, thus leading to a decrease both in the length of hospital stay (p-value

Review efficacy and safety of minimally-invasive treatments for Low Urinary Tract Symptoms (LUTS) in patients affected by Benign Prostate Hyperplasia (BPH). We performed a systematic review of the literature from 1993 to 2022 leveraging original research articles, reviews, and case-studies published in peer-reviewed journals and stored in public repositories. Prostate artery embolization (PAE), transurethral needle ablation (TUNA), transurethral microwave thermotherapy (TUMT), high intensity focused ultrasound (HIFU), laser treatments and Cryoablation are valid and safe alternatives to the gold standard (surgery) in the treatment of LUTS in patients affected by BPH, with fewer undesired effects being reported.

Abstract Photodynamic therapy (PDT) is an anticancer treatment involving administration of a tumour-localizing photosensitizer, followed by activation by light of a suitable wavelength. In previous work, we showed that the natural anthraquinone (AQ) Parietin (PTN), was a promising photosensitizer for photodynamic therapy of leukemic cells in vitro. The present work aimed to analyze the photosensitizing ability of PTN in the mammary carcinoma LM2 cells in vitro and in vivo in a model of subcutaneously implanted tumours. Photodynamic therapy mediated by parietin (PTN-PDT) (PTN 30 µM, 1 h and 1.78 J/cm2 of blue light) impaired cell growth and migration of LM2 cells in vitro. PTN per se induced a significant decrease in cell migration, and it was even more marked after illumination (migration index was 0.65 for PTN and 0.30 for PTN-PDT, *p

Histamine (HA) is a potent mediator that plays a central role in inflammation and allergy, acting through four G-protein-coupled receptors (i.e. H1–H4). HA is an accepted promoter of type 2 immunity in CD4+ T cells during hypersensitivity. Previously, we demonstrated that HA can promote antigen cross-presentation, inducing the activation of antigen-specific CD8+ T cells in an asthmatic murine model. Non-classical CD8+ T-cell profiles, such as Tc2 or Tc17, are associated with allergic disease persistence and chronicity. In this paper, we focus on the role of the H3 receptor (H3R) and the H4 receptor (H4R) in the development of allergic contact dermatitis. We were able to show that induction of the type 2 profiles associated with interleukin 13 production, both by CD4 and CD8 lymphocytes, depend on the interaction of HA with H3R and H4R. Blocking both receptors using the selective H3/H4 receptor antagonist thioperamide or the selective H4R ligand JNJ777120 reduces the inflammatory response, inducing an immunosuppressive profile associated with the increased proportion of FOXp3+ regulatory T lymphocytes and CD11b+Gr-1+ myeloid suppressor cells. Interestingly, in dendritic cells, only H4R blockade, and not H3R blockade, is capable of modulating most of the inflammatory effects observed in our model.

Budd–Chiari syndrome (BCS) is a rare clinical entity characterized by hepatic venous outflow obstruction, resulting in liver congestion and subsequent chronic parenchymal damage. This condition often leads to the development of focal liver lesions, including benign focal nodular hyperplasia-like regenerative nodules, hepatocellular carcinoma, and perfusion-related pseudo-lesions. Computed tomography, ultrasound, and magnetic resonance are the commonly employed imaging modalities for the follow-up of BCS patients and for the detection and characterization of new-onset lesions. The accurate differentiation between benign and malignant nodules is crucial for optimal patient management and treatment planning. However, it can be challenging due to the variable and overlapping characteristics observed. This review aims to provide a comprehensive overview of the imaging features and differential diagnosis of focal liver lesions in BCS, emphasizing the key findings and discussing the challenges associated with their interpretation, with the purpose of facilitating the subsequent clinical decision-making.

Introduction Several studies show that soft tissue sarcoma patients undergoing surgery may experience reduced functional outcome and quality of life compared to the average population. Aim The aim of this case report is to show how an interactive platform, BoboPro, could be used as a supplementary instrumentation in assessment and treatment of balance and proprioceptive de cits. Materials and methods The patient had a mixoid liposacoma of the posterior compartment of the thigh and underwent a surgical resection of part of the sartorius, gracilis, semimembranosus muscles and semitendinosus muscle tendon. Three months after surgery he was assessed by our rehabilitation service. After evaluation through physical examination, validated scales and the interactive platform BoboPro with static and dynamic tests, he was found to have limited range of motion of knee and mild disturbance of double-leg stance balance and one-leg stance. Then the patient began a personalized rehabilitation treatment. At the end a new assessment was performed. Results After the rehabilitation treatment the patient showed an improvement in articularity and strenght of the lower limb treated with surgery. In the BoboPro system tests there was an improvement of about 30% in terms of accuracy in keeping the double-leg stance and of about 15% in the left-leg stance. Conclusion The peculiarity of our case is that BoboProallowed to point out a mild balance de cit and its improvement after rehabilitation exercise, even if it is not a standardized system. Its intuitive graphic feedback contributed to improve the patient’s compliance. This case report shows that BoboPro is an interesting tool as far as practicity and versatility is concerned.

Neuroendocrine neoplasms (NENs) are a diverse group of tumors with varying clinical behaviors. Their incidence has risen due to increased awareness, improved diagnostics, and aging populations. The 2019 World Health Organization classification emphasizes integrating radiology and histopathology to characterize NENs and create personalized treatment plans. Imaging methods like CT, MRI, and PET/CT are crucial for detection, staging, treatment planning, and monitoring, but each of them poses different interpretative challenges and none are immune to pitfalls. Treatment options include surgery, targeted therapies, and chemotherapy, based on the tumor type, stage, and patient-specific factors. This review aims to provide insights into the latest developments and challenges in NEN imaging, diagnosis, and management. [ABSTRACT FROM AUTHOR]

Abstract Background Radiomics is expected to improve the management of metastatic colorectal cancer (CRC). We aimed at evaluating the impact of liver lesion contouring as a source of variability on radiomic features (RFs). Methods After Ethics Committee approval, 70 liver metastases in 17 CRC patients were segmented on contrast-enhanced computed tomography scans by two residents and checked by experienced radiologists. RFs from grey level co-occurrence and run length matrices were extracted from three-dimensional (3D) regions of interest (ROIs) and the largest two-dimensional (2D) ROIs. Inter-reader variability was evaluated with Dice coefficient and Hausdorff distance, whilst its impact on RFs was assessed using mean relative change (MRC) and intraclass correlation coefficient (ICC). For the main lesion of each patient, one reader also segmented a circular ROI on the same image used for the 2D ROI. Results The best inter-reader contouring agreement was observed for 2D ROIs according to both Dice coefficient (median 0.85, interquartile range 0.78–0.89) and Hausdorff distance (0.21 mm, 0.14–0.31 mm). Comparing RF values, MRC ranged 0–752% for 2D and 0–1567% for 3D. For 24/32 RFs (75%), MRC was lower for 2D than for 3D. An ICC > 0.90 was observed for more RFs for 2D (53%) than for 3D (34%). Only 2/32 RFs (6%) showed a variability between 2D and circular ROIs higher than inter-reader variability. Conclusions A 2D contouring approach may help mitigate overall inter-reader variability, albeit stable RFs can be extracted from both 3D and 2D segmentations of CRC liver metastases.

Abstract Background Radiation dose in computed tomography (CT) has become a topic of high interest due to the increasing numbers of CT examinations performed worldwide. Hence, dose tracking and organ dose calculation software are increasingly used. We evaluated the organ dose variability associated with the use of different software applications or calculation methods. Methods We tested four commercial software applications on CT protocols actually in use in our hospital: CT-Expo, NCICT, NCICTX, and Virtual Dose. We compared dose coefficients, estimated organ doses and effective doses obtained by the four software applications by varying exposure parameters. Our results were also compared with estimates reported by the software authors. Results All four software applications showed dependence on tube voltage and volume CT dose index, while only CT-Expo was also dependent on other exposure parameters, in particular scanner model and pitch caused a variability till 50%. We found a disagreement between our results and those reported by the software authors (up to 600%), mainly due to a different extent of examined body regions. The relative range of the comparison of the four software applications was within 35% for most organs inside the scan region, but increased over the 100% for organs partially irradiated and outside the scan region. For effective doses, this variability was less evident (ranging from 9 to 36%). Conclusions The two main sources of organ dose variability were the software application used and the scan region set. Dose estimate must be related to the process used for its calculation.

El cambio climático obliga a mejorar la eficiencia del consumo de energía. En este trabajo se desarrolla una metodología de evaluación energética y económica de las ventajas de sustituir sistemas de calefacción tradicionales de gas natural, GLP, o electricidad, por una moderna bomba de calor (inverter). Al ser su eficiencia función de la diferencia de temperaturas entre el ambiente exterior y el interior, la eficiencia varía según la ubicación de la ciudad. De esta manera, se estudia su rendimiento en Bariloche, Santiago de Chile y Montevideo (temperatura media anual de 8,3; 14,6 y 16,3 °C, respectivamente), empleando los siguientes sistemas: 1) aire-aire, instalando varios equipos Split; y 2) aire-agua, instalando una bomba de calor que brinde calefacción por radiadores de agua. Esta metodología permite dimensionar estos sistemas y calcular el ahorro anual, ejemplificándose para una vivienda social de 50 m2. En todos los casos estudiados se alcanzaron reducciones de los consumos y ahorros de moderados a notables (y períodos de repago de la inversión menores a dos años), excepto contra el gas natural en Bariloche y Montevideo. Se discute también cómo su inversión moderada puede constituir una primera solución asequible, frente a la costosa rehabilitación térmica, a fin de obtener viviendas más sustentables.

No artigo, propõe-se demonstrar a influência decisiva exercida pelas leituras de Benedetto Croce nas impressões de Gramsci sobre a obra de Giambattista Vico. Para isso, explora-se os trechos dos Cadernos do Cárcere onde Gramsci faz referências ao iluminista italiano. Com base nessas demonstrações, argumenta-se que, no movimento de assimilação e afastamento da filosofia de Croce, Gramsci termina por subsumir a filosofia à política em sua elaboração da filosofia da práxis.

A 48-year-old female presented to the emergency department with chest pain and collapsed at the front desk. She was reanimated with mechanical chest compression, and after coronary angiography, a left anterior descending/diagonal bifurcation mini-crush stenting was performed. Few hours after the procedure, the patient showed severe hypotension. Abdominal ultrasound and computed tomography (CT) scan evidenced a massive subcapsular liver hematoma (Grade IV, American association for the surgery of trauma (AAST) liver injury scale) of the right lobe with extrahepatic blushing. Transhepatic embolization was attempted but without benefit, so the patient underwent emergency laparotomy for damage control surgery with perihepatic packing. After hemodynamic stabilization, right hepatectomy was performed with a favorable outcome and full recovery. The patient CT scan was retrospectively processed to obtain a virtual model visualizable through a head-mounted display. The virtual reconstruction could improve the comprehension of the injury and the liver surgical anatomy for educational purpose, and it could represent a new tool for preoperative planning.

Abstract Background To manage and analyse dosimetric data provided by computed tomography (CT) scanners from four Italian hospitals. Methods A radiation dose index monitoring (RDIM) software was used to collect anonymised exams stored in a cloud server. Since hospitals use different names for the same procedure, digital imaging and communications in medicine (DICOM) tags more appropriate to describe exams were selected and associated to study common names (SCNs) from a radiology playbook according to scan region and use of contrast media. Retrospective analysis was carried out to describe population and to evaluate dosimetric indexes and inaccuracies associated with SCNs. Results More than 400 procedures were clustered into 95 SCNs, but 78% of exams on adults were described with only 10 SCNs. Median values of dose-length product (DLP) and volumetric CT dose index (CTDIvol) for three analysed SCNs were in agreement with those previously published. The percentage of inaccuracies does not heavily affect the dosimetric analysis on the whole cloud, since variations in median values reached at most 8%. Conclusions Implementation of a cloud-based RDIM software and related issues were described, showing the strength of the chosen playbook-based clustering and its usefulness for homogeneous data analysis. This approach may allow for optimisation actions, accurate assessment of the risk associated with radiation exposure, comparison of different facilities, and, last but not least, collection of information for the implementation of the 2013/59 Euratom Directive.

This article reflects on the need to define the time of the pandemic as an entirely new time, a separate and distinct era. A radical and global change seems to have been evoked – invoked, desired – since the beginning of the quarantine. Auspices, evocations that clash, however, with many signs offered by the present days: certainly nothing has changed, and nothing seems to have to change, in the lives of many people, deprived of their rights and dignity.

Background HER2 is a therapeutic target for metastatic colorectal cancer (mCRC), as demonstrated in the pivotal HERACLES-A (HER2 Amplification for Colo-rectaL cancer Enhanced Stratification) trial with trastuzumab and lapatinib. The aim of HERACLES-B trial is to assess the efficacy of the combination of pertuzumab and trastuzumab-emtansine (T-DM1) in this setting.Methods HERACLES-B was a single-arm, phase II trial, in patients with histologically confirmed RAS/BRAF wild-type and HER2+ mCRC refractory to standard treatments. HER2 positivity was assessed by immunohistochemistry and in situ hybridisation according to HERACLES criteria. Patients were treated with pertuzumab (840 mg intravenous load followed by 420 mg intravenous every 3 weeks) and T-DM1 (3.6 mg/kg every 3 weeks) until disease progression or toxicity. Primary and secondary end points were objective response rate (ORR) and progression-free survival (PFS). With a Fleming/Hern design (H0=ORR 10%; α=0.05; power=0.85), 7/30 responses were required to demonstrate an ORR ≥30% (H1).Results Thirty-one patients, 48% with ≥4 lines of previous therapies, were treated and evaluable. ORR was 9.7% (95% CI: 0 to 28) and stable disease (SD) 67.7% (95% CI: 50 to 85). OR/SD ≥4 months was associated with higher HER2 immunohistochemistry score (3+ vs 2+) (p = 0.03). Median PFS was 4.1 months (95% CI: 3.6 to 5.9). Drug-related grade (G) 3 adverse events were observed in two patients (thrombocytopaenia); G≤2 AE in 84% of cycles (n = 296), mainly nausea and fatigue.Conclusions HERACLES-B trial did not reach its primary end point of ORR; however, based on high disease control, PFS similar to other anti-HER2 regimens, and low toxicity, pertuzumab in combination with T-DM1 can be considered for HER2+mCRC as a potential therapeutic resource.Trial registration number 2012-002128-33 and NCT03225937.

Purpose: Advanced triple negative breast cancer (ATNBC) is defined by a lack of expression of hormones receptors as well as HER2/neu and its high probability of visceral metastasis. This pathology is associated with a poor prognosis. Previously, we found that T2, an N4-arylsubstituted thiosemicarbazone (N4-TSC), had cytotoxic effect on human breast cancer cells lines. Hence, in this study, we investigated the anti-metastasic action of T2 on ATNBC. Methods: In order to deepen T2 action mode on ATNBC, we first confirmed T2 cytotoxicity on a panel of TNBC cells and then continued studying T2 effects in vitro an in vivo on the syngeneic 4T1 mouse model. Results: We found that T2 had a cytotoxic effect comparable to chemotherapeutics used in present treatment schemes for ATNBC. T2 treatment not only induced apoptosis, but it also down-modulated 4T1 invasive and metastatic-associated capacities, such as clonogenicity, migration and metallo-proteases activity. Moreover, this agent reduced the number of 4T1 cancer stem cells. Finally, T2 treatment induced a more differentiated cell phenotype and the overexpression of the metastasis suppressor gene NDRG-1. In vivo assays showed that T2 reduced tumor burden, down modulated local tumor invasion and significantly reduced the number of lung metastases in the 4T1 advanced TNBC murine model, while the compound did not exhibit intolerable toxicity. Conclusion: This study provided evidence that T2 not only exerted an anti-tumor activity but it also showed anti-invasive and anti-metastatic actions on ATNBC in vivo and in vitro, suggesting that T2 could be considered as a promising therapy that deserves further analysis.

Resumen Este trabajo presenta un modelo térmico y su código numérico para calcular el consumo energético de calentadores eléctricos con tanque de agua para uso en el hogar. Se estudian varias estrategias de ahorro mediante dispositivos de control y nuevas configuraciones que implican la instalación de hasta tres calentadores. Se obtuvieron ahorros significativos de energía, tanto para un único usuario (675 kW·h/año), como para una familia de seis personas (2200 kW·h/año). Se estudian ahorros económicos y tiempo de repago de equipos para Argentina, aunque las conclusiones pueden fácilmente extrapolarse a otros países. Abstract This work introduces a thermal model and its numerical code to compute the household energy consumption related to domestic water heaters that use a tank. Here are studied several strategies for energy saving by means of using controlling devices and new configurations by installing up to three water heaters. This way, it was achieved noticeable saving, ranging from 675 kW·h per year (for one dweller) to 2200 kW·h per year (for a six-person family). Economic savings and equipment repayment time for Argentina are studied, although the conclusions can easily be extrapolated to other countries. https://doi.org/10.22209/rt.v43n2a01

Bladder cancer (BC) is the ninth most common cancer worldwide, but molecular changes are still under study. During tumor progression, Epithelial cadherin (E-cadherin) expression is altered and β-catenin may be translocated to the nucleus, where it acts as co-transcription factor of tumor invasion associated genes. This investigation further characterizes E-cadherin and β-catenin associated changes in BC, by combining bioinformatics, an experimental murine cell model (MB49/MB49-I) and human BC samples. In in silico studies, a DisGeNET (gene-disease associations database) analysis identified CDH1 (E-cadherin gene) as one with highest score among 130 BC related-genes. COSMIC mutation analysis revealed CDH1 low mutations rates. Compared to MB49 control BC cells, MB49-I invasive cells showed decreased E-cadherin expression, E- to P-cadherin switch, higher β-catenin nuclear signal and lower cytoplasmic p-Ser33-β-catenin signal, higher Ephrin-B1 ligand and EphB2 receptor expression, higher Phospho-Stat3 and Urokinase-type Plasminogen Activator (UPA), and UPA receptor expression. MB49-I cells transfected with Ephrin-B1 siRNA showed lower migratory and invasive capacity than control cells (scramble siRNA). By immunohistochemistry, orthotopic MB49-I tumors had lower E-cadherin, increased nuclear β-catenin, lower pSer33-β-catenin cytoplasmic signal, and higher Ephrin-B1 expression than MB49 tumors. Similar changes were found in human BC tumors, and 83% of infiltrating tumors depicted a high Ephrin-B1 stain. An association between higher Ephrin-B1 expression and higher stage and tumor grade was found. No association was found between abnormal E-cadherin signal, Ephrin-B1 expression or clinical-pathological parameter. This study thoroughly analyzed E-cadherin and associated changes in BC, and reports Ephrin-B1 as a new marker of tumor aggressiveness.