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BACKGROUND & AIMS: Metabolic syndrome (MS) is a growing epidemic and a risk factor for the development of hepatocellular carcinoma (HCC). This study investigated the long-term outcomes of liver resection (LR) for HCC in patients with MS. Rates, timing, patterns, and treatment of recurrences were investigated, and cancer-specific survivals were assessed. METHODS: Between 2001 and 2021, data from 24 clinical centers were collected. Overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival were analyzed as well as recurrence patterns and treatment. The analysis was conducted using a competing-risk framework. The trajectory of the risk of recurrence over time was applied to a competing risk analysis. For post-recurrence survival, death resulting from tumor progression was the primary endpoint, whereas deaths with recurrence relating to other causes were considered as competing events. RESULTS: In total, 813 patients were included in the study. Median OS was 81.4 months (range 28.1-157.0 months), and recurrence occurred in 48.3% of patients, with a median RFS of 39.8 months (range 15.7-174.7 months). Cause-specific hazard of recurrence showed a first peak 6 months (0.027), and a second peak 24 months (0.021) after surgery. The later the recurrence, the higher the chance of receiving curative intent approaches (p = 0.001). Size >5 cm, multiple tumors, microvascular invasion, and cirrhosis were independent predictors of recurrence showing a cause-specific hazard over time. RFS was associated with death for recurrence (hazard ratio: 0.985, 95% CI: 0.977-0.995; p = 0.002). CONCLUSIONS: Patients with MS undergoing LR for HCC have good long-term survival. Recurrence occurs in 48% of patients with a double-peak incidence and time-specific hazards depending on tumor-related factors and underlying disease. The timing of recurrence significantly impacts survival. Surveillance after resection should be adjusted over time depending on risk factors. IMPACT AND IMPLICATIONS: Metabolic syndrome (MS) is a growing epidemic and a significant risk factor for the development of hepatocellular carcinoma (HCC). The present study demonstrated that patients who undergo surgical resection for HCC on MS have a good long-term survival and that recurrence occurs in almost half of the cases with a double peak incidence and time-specific hazards depending on tumor-related factors and underlying liver disease. Also, the timing of recurrence significantly impacts survival. Clinicians should therefore adjust follow-up after surgery accordingly, considering timing of recurrence and specific risk factors. Also, the results of the present study might help design future trials on the use of adjuvant therapy following resection.

Summary: Background & Aims: Nutritional impairments may negatively impact different outcomes, including survival, in patients with thoracic malignancies. Despite this, a low number of patients are screened for nutritional risk and referred to an appropriate service. The aim of this study is to evaluate the feasibility of an Assess-Advise-Refer approach to implementing the engagement of the medical staff to refer patients at nutritional risk to a dedicated dietician. Methods: Thoracic oncologists were trained to: i) administer the Nutritional Risk Screening (NRS-2002) tool to the patients during the first oncological evaluation to identify the nutritional risk, ii) advise patients about the importance of nutrition in cancer, and iii) refer patients at nutritional risk to the dedicated dietetic service. Results: Between July 2022 and February 2023, 40% of patients scheduled for a first oncological evaluation received nutritional screening from oncologist. All the screened patients were advised about the importance of nutritional aspects during cancer care. Overall, seven patients were detected at nutritional risk and referred to the dietetic service. Additionally, other four patients were referred to the dietitian upon their request. Conclusion: Whereas advice and referral appear to be better implemented, nutritional screening needs to be more integrated into the clinical practice routine.

Liver transplantation (LT) is a potentially curative experimental treatment for unresectable intrahepatic cholangiocarcinoma (iCC). Pre-transplant downstaging may help defining tumor aggressiveness and drive patient selection. We report the preliminary results of LT for liver-limited unresectable iCC after sequential downstaging with systemic chemotherapy and radioembolization (SYS-TARE). In case of sustained disease stability after SYS-TARE, patients underwent surgical nodal sampling and, if negative, were listed for LT. In this study, 13 patients with unresectable iCC underwent downstaging with SYS-TARE. The median age was 70 years and 77% were female. All had single bulky lesions at diagnosis. After SYS-TARE, 9 (69%) dropped out: 3 due to progressive disease after TARE with no response to second-line, 4 due to extrahepatic disease development and 2 due to positive nodal disease at pre-listing abdominal exploration. The median OS after dropout was 11.5 months. Four (31%) were successfully listed and transplanted. At pathology, viable tumor ranged from 30% to less than 5%. All four patients are alive and disease-free at 73, 40, 12, and 8 months from LT. LT for unresectable iCC after downstaging with SYS-TARE appears to select suitable patients for LT, achieving optimal oncological outcomes in case of response to therapy and no lymphnodal spread.

Introdução A comunicação em saúde possui um papel crucial no processo terapêutico do paciente nas unidades de internamento, desse modo é necessário desenvolver um vínculo entre profissionais de saúde que prestam o cuidado, o paciente e/ou seus respetivos acompanhantes. Uma comunicação falha pode resultar em complicações no tratamento, afetando tanto o paciente quanto a equipe de saúde responsável pelo cuidado. Objetivo Investigar a perceção do paciente sobre a comunicação em saúde. Métodos Abordagem quantitativa, realizado com pacientes de idade superior a 18 anos, com mais de 24 horas de internamento em enfermaria, de um hospital de alta complexidade, localizado na região noroeste do estado do Paraná. Resultados Totalizou 98 pacientes, sendo 58% mulheres, idade x ̅ = 66,4; 6,6 anos de estudo; tempo médio de internamento de quatro dias. A perceção quanto a comunicação foi satisfatória: equipe médica (93,9%); enfermagem (96,9%); informação sobre o motivo de realizar exame laboratorial (63,3%); questionamento sobre presença de reação alérgica (77,6%). Oportunidades de melhoria nesse processo: tratamento programado (16,3%); necessidade de realizar exame laboratorial (59,2%); e, informação sobre os possíveis efeitos colaterais de medicamentos (31,6%). Conclusão A perceção dos pacientes sobre a comunicação foi positiva. Contudo, observou-se fragilidades que podem culminar em falhas assistenciais.

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is linked to high mortality, primarily through an intense inflammatory response. Diacerein has emerged as a potential therapy for COVID-19 due to its potential impact in decreasing the inflammasome activation and coronavirus replication. This study aims to explore diacerein’s influence in inhibiting both viral replication and the inflammatory response after SARS-CoV-2 infection.MethodsHuman peripheral blood mononuclear cells (PBMCs) were obtained from healthy volunteers and infected in vitro with SARS-CoV-2. Additionally, we carried out a pilot randomized, double-blind, placebo-controlled study with 14 participants allocated to diacerein (n = 7) or placebo (n = 7) therapies every 12 h for 10 days. The primary endpoint was change in plasma markers of inflammasome activation (NLRP3, caspase-1, and gasdermin-D).ResultsIn vitro protocols have shown that rhein, diacerein’s primary metabolite, decreased IL-1β secretion caused by SARS-CoV-2 infection in human PBMCs (p < 0.05), and suppressed viral replication when administered either before or after the virus incubation (p < 0.05). This later effect was, at least partially, attributed to its inhibitory effect on 3-chymotrypsin-like protease (SARS-CoV-2 3CLpro) and papain-like protease in the SARS-CoV-2 (SARS-CoV-2 PLpro) virus and in the phosphorylation of proteins related cytoskeleton network (p < 0.05). Diacerein-treated COVID-19 patients presented a smaller area under the curve for NLRP3, caspase-1 and GSDM-D measured on days 2, 5, and 10 after hospitalization compared to those receiving a placebo (p < 0.05).ConclusionThe indicated mechanisms of action of diacerein/rhein can reduce viral replication and mitigate the inflammatory response related to SARS-CoV-2. These findings are preliminary and require confirmation in clinical trials.

El edificio en Virrey Avilés y los Pequeños Condominios Familiares se diseñan desde las constricciones de sus respectivos sitios. El primero ocupa un lote típico de Buenos Aires, con un ancho de 8,66 metros, donde las circulaciones y espacios colectivos se organizan hacia el interior de la manzana. Una escalera en medio del patio difumina los límites entre los espacios comunes y los exteriores de uso de cada unidad. Los Pequeños Condominios Familiares se construyen en lotes de la Operación Sitio de 9 metros de ancho por 18 metros de largo. En ellos, se levanta un edificio de dos a tres pisos que busca sacar del hacinamiento a familias de allegados. Tipologías adaptables y tecnologías de prefabricación minimizan los tiempos de construcción, evitando alejar a las familias del sitio por más de 6 meses. Los potenciales ámbitos de colectividad en torno a la vivienda tampoco se limitan a sus condiciones espaciales. En ambos casos, la gestión y el diseño de la vivienda colectiva van acompañados de la formación de nuevos regímenes de copropiedad y cofinanciamiento.

The Apartment Building in Virrey Avilés and the Small Family Cohousing are shaped by the constraints of their respective sites. The former occupies a typical lot in Buenos Aires, with a width of 8.66 meters, where circulations and collective spaces are organized towards the center of the urban block. A staircase in the middle of the courtyard blurs the boundaries between common spaces and the external areas designated for each unit’s use. The Small Family Cohousing projects are designed for plots stemming from the historic Site Operation in Santiago, measuring 9 meters wide by 18 meters long. Within them, a building of two to three stories is erected to alleviate overcrowding for multiple families currently living under one roof. The use of adaptable typologies and prefabrication technologies minimizes construction timelines, ensuring that the families remain away from their site for no longer than 6 months. Moreover, in both cases, architectural design is intertwined with the establishment of new paradigms of co-ownership and co-financing, serving as a testament that the pursuit of collectivity in housing transcends mere spatial considerations.

Abstract Background Glucagon-like peptide 1 receptor agonists have been proven to be effective in adults with diabetes and children with obesity. However, children with type 2 diabetes constitute an underrepresented subpopulation with limited treatment options. This meta-analysis aimed to determine more precise estimates of the efficacy and safety of glucagon-like peptide-1 agonists in pediatric type 2 diabetes mellitus. Methods Three databases were searched (PubMed, Embase, and Cochrane Central Register of Controlled Trials) for trials published until the end of March 2024. The search indexing terms included 3 categories: [1] type 2 diabetes mellitus [2], youth, and [3] glucagon-like peptide-1 receptor agonist (GLP-1 RA). Randomized controlled trials in youth with type 2 diabetes (age ≤ 18 years) that assessed anthropometric and metabolic parameters were included. A total of 1119 nonduplicate studies were retrieved, and 137 full-text articles were screened. The data were analyzed using mean differences (MDs) with 95% CIs and odds ratios (ORs) with 95% CIs. For outcomes with low heterogeneity, a fixed-effects model was used. Otherwise, we applied a random effects model. Our outcomes were Hb1Ac, fasting blood glucose (FBG), blood pressure, weight, and side effects. Results Five studies comprehending 415 children and adolescents were included. On average, GLP-1 RA reduced HbA1c levels (-1.01%; 95% CI, -1.26 to -0.76), fasting blood glucose levels (-1.88 mmol/L; 95% CI, -2.51 to -1.26), and body weight (-1.6 kg; 95% CI, -2.83 to -0.36). No significant reductions in systolic blood pressure (MD -0.19 mmHg; 95% CI, -3.9 to 3.52 mmHg) or diastolic blood pressure (MD 0.3 mmHg; 95% CI, -2.33 to 2.93 mmHg) were observed. Despite a higher incidence of side effects, withdrawal rates from the studies remained low. Conclusions Within this specific population, GLP-1 RAs exhibit a notable association with substantial reductions in HbA1c, FBG, and body weight. The administration of these medications is concurrent with an elevated incidence of side effects, which are predominantly gastrointestinal and tolerable. Trial registration PROSPERO identifier: CRD42023393020.

Abstract Background Biliary tract cancers (BTCs) are rare and lethal cancers, with a 5-year survival inferior to 20%(1–3). The only potential curative treatment is surgical resection. However, despite complex surgical procedures that have a remarkable risk of postoperative morbidity and mortality, the 5-year survival rate after radical surgery (R0) is 20–40% and recurrence rates are up to ~ 75%(4–6). Up to ~ 40% of patients relapse within 12 months after resection, and half of these patient will recur systemically(4–6). There is no standard of care for neoadjuvant chemotherapy (NAC) in resectable BTC, but retrospective reports suggest its potential benefit (7, 8). Methods PURITY is a no-profit, multicentre, randomized phase II/III trial aimed at evaluating the efficacy of the combination of gemcitabine, cisplatin and nabpaclitaxel (GAP) as neoadjuvant treatment in patients with resectable BTC at high risk for recurrence. Primary objective of this study is to evaluate the efficacy of neoadjuvant GAP followed by surgery as compared to upfront surgery, in terms of 12-month progression-free survival for the phase II part and of progression free survival (PFS) for the phase III study. Key Secondary objectives are event free survival (EFS), relapse-free survival, (RFS), overall survival (OS), R0/R1/R2 resection rate, quality of life (QoL), overall response rate (ORR), resectability. Safety analyses will include toxicity rate and perioperative morbidity and mortality rate. Exploratory studies including Next-Generation Sequencing (NGS) in archival tumor tissues and longitudinal ctDNA analysis are planned to identify potential biomarkers of primary resistance and prognosis. Discussion Considering the poor prognosis of resected BTC experiencing early tumor recurrence and the negative prognostic impact of R1/R2 resections, PURITY study is based on the rationale that NAC may improve R0 resection rates and ultimately patients’ outcomes. Furthermore, NAC should allow early eradication of microscopic distant metastases, undetectable by imaging but already present at the time of diagnosis and avoid mortality and morbidity associated with resection for patients with rapid progression or worsening general condition during neoadjuvant therapy. The randomized PURITY study will evaluate whether patients affected by BTC at high risk from recurrence benefit from a neoadjuvant therapy with GAP regimen as compared to immediate surgery. Trial registration PURITY is registered at ClinicalTrials.gov (NCT06037980) and EuCT(2023–503295-25–00).

AbstractBackground The Covid-19 pandemic has affected patients with end-stage kidney disease (ESKD). Whether dialysis parameters have a prognostic value in ESKD patients with Covid-19 remains unclear.Materials and Methods We retrospectively evaluated clinical characteristics, blood pressure (BP) and dialysis parameters in ESKD patients undergoing maintenance outpatient hemodialysis, with (Covid-ESKD) and without (No-Covid-ESKD) Covid-19, at four Brazilian hemodialysis facilities. The Covid-ESKD (n = 107; 54% females; 60.8 ± 17.7 years) and No-Covid-ESKD (n = 107; 62% females; 58.4 ± 14.6 years) groups were matched by calendar time. The average BP and dialysis parameters were calculated during the pre-infection, acute infection, and post-infection periods. The main outcomes were Covid-19 hospitalization and all-cause mortality.Results Covid-ESKD patients had greater intradialytic and postdialysis systolic BP and lower predialysis weight, postdialysis weight, ultrafiltration rate, and interdialytic weight gain during acute-illness compared to 1-week-before-illness, while these changes were not observed in No-Covid-ESKD patients. After 286 days of follow-up (range, 276–591), there were 18 Covid-19-related hospitalizations and 28 deaths among Covid-ESKD patients. Multivariable logistic regression analysis showed that increases in predialysis systolic BP from 1-week-before-illness to acute-illness (OR, 95%CI = 1.06, 1.02–1.10; p = .004) and Covid-19 vaccination (OR, 95%CI = 0.16, 0.04–0.69; p = .014) were associated with hospitalization in Covid-ESKD patients. Multivariable Cox-regression analysis showed that Covid-19-related hospitalization (HR, 95%CI = 5.17, 2.07–12.96; p

Abstract The accumulation of advanced glycation end-products (AGEs) elicits morphofunctional kidney impairment. AGEs levels can be noninvasively estimated by skin autofluorescence (SAF). We explored whether high SAF predicts kidney outcomes in type 2 diabetes (T2D) individuals. The study was conducted as a predefined analysis of the Brazilian Diabetes Study, a prospective single-center cohort of T2D adults. Data from 155 individuals followed for up to 1716 days were considered. The incidence of major adverse kidney events (MAKE) was 9.6%. Individuals with above-median SAF had a higher incidence of MAKEs (4.6% vs. 21%; p = 0.002), with an HR of 3.39 [95% CI: 1.06–10.85; p = 0.040] after adjustment by age and gender. The mean adjusted eGFR change was 1.08 units (SE: 1.15; 95%CI: –1.20, 3.37) in the low SAF and –5.19 units [SE: 1.93; 95%CI: –9.10, –1.29] in the high SAF groups (between-subject difference: F: 5.62, p = 0.019). The high-SAF group had a greater prevalence of rapid decliners than the low-SAF group (36.7% vs. 15.8%; p = 0.028). In conclusion, high SAF was related to increased incidence of MAKEs and faster decline in eGFR among T2D subjects. This should be considered by healthcare providers when identifying individuals more prone to diabetes-related kidney complications.

Background 123Iodine‐meta‐iodobenzylguanidine scintigraphy is useful for assessing cardiac autonomic dysfunction and predict outcomes in heart failure (HF). The relationship of cardiac sympathetic function with myocardial remodeling and diffuse fibrosis remains largely unknown. We aimed to evaluate the cardiac sympathetic function of patients with HF and its relation with myocardial remodeling and exercise capacity. Methods and Results Prospectively enrolled patients with HF (New York Heart Association class II–III) were stratified into HF with preserved left ventricular ejection fraction [LVEF] ≥45%) and reduced LVEF. Ventricular morphology/function and myocardial extracellular volume (ECV) fraction were quantified by cardiovascular magnetic resonance, global longitudinal strain by echocardiography, cardiac sympathetic function by heart‐to‐mediastinum ratio from 123iodine‐meta‐iodobenzylguanidine scintigraphy. All participants underwent cardiopulmonary exercise testing. The cohort included 33 patients with HF with preserved LVEF (LVEF, 60±10%; NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide], 248 [interquartile range, 79–574] pg/dL), 28 with HF with reduced LVEF (LVEF, 30±9%; NT‐proBNP, 743 [interquartile range, 250–2054] pg/dL) and 20 controls (LVEF, 65±5%; NT‐proBNP, 40 [interquartile range, 19–50] pg/dL). Delayed (4 hours) 123iodine‐meta‐iodobenzylguanidine heart‐to‐mediastinum ratio was lower in HF with preserved LVEF (1.59±0.25) and HF with reduced LVEF (1.45±0.16) versus controls (1.92±0.24; P

IntroductionTo date, for all non-small cell lung cancer (NSCLC) cases, it is recommended to test for driver alterations to identify actionable therapeutic targets. In this light, comprehensive genomic profiling (CGP) with next generation sequencing (NGS) has progressively gained increasing importance in clinical practice. Here, with the aim of assessing the distribution and the real-world frequency of gene alterations and their correlation with patient characteristics, we present the outcomes obtained using FoundationOne (F1CDx) and FoundationLiquid CDx (F1L/F1LCDx) NGS-based profiling in a nationwide initiative for advanced NSCLC patients.MethodsF1CDx (324 genes) was used for tissue samples, and F1L (70 genes) or F1LCDx (324 genes) for liquid biopsy, aiming to explore the real-world occurrence of molecular alterations in aNSCLC and their relationship with patients’ characteristics.ResultsOverall, 232 advanced NSCLC patients from 11 Institutions were gathered [median age 63 years; never/former or current smokers 29.3/65.9%; adenocarcinoma/squamous 79.3/12.5%; F1CDx/F1L+F1LCDx 59.5/40.5%]. Alterations were found in 170 different genes. Median number of mutated genes per sample was 4 (IQR 3–6) and 2 (IQR 1–3) in the F1CDx and F1L/F1LCDx cohorts, respectively. TP53 (58%), KRAS (22%), CDKN2A/B (19%), and STK11 (17%) alterations were the most frequently detected. Actionability rates (tier I and II) were comparable: 36.2% F1CDx vs. 34% ctDNA NGS assays (29.5% and 40.9% F1L and F1LCDx, respectively). Alterations in KEAP1 were significantly associated with STK11 and KRAS, so as TP53 with RB1. Median tumor mutational burden was 6 (IQR 3–10) and was significantly higher in smokers. Median OS from metastatic diagnosis was 23 months (IQR 18.5–19.5) and significantly lower in patients harboring ≥3 gene mutations. Conditional three-year survival probabilities increased over time for patients profiled at initial diagnosis and exceeded those of individuals tested later in their clinical history after 12 months.ConclusionThis study confirms that NGS-based molecular profiling of aNSCLC on tissue or blood samples offers valuable predictive and prognostic insights.

Background & Aims: Metabolic syndrome (MS) is a growing epidemic and a risk factor for the development of hepatocellular carcinoma (HCC). This study investigated the long-term outcomes of liver resection (LR) for HCC in patients with MS. Rates, timing, patterns, and treatment of recurrences were investigated, and cancer-specific survivals were assessed. Methods: Between 2001 and 2021, data from 24 clinical centers were collected. Overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival were analyzed as well as recurrence patterns and treatment. The analysis was conducted using a competing-risk framework. The trajectory of the risk of recurrence over time was applied to a competing risk analysis. For post-recurrence survival, death resulting from tumor progression was the primary endpoint, whereas deaths with recurrence relating to other causes were considered as competing events. Results: In total, 813 patients were included in the study. Median OS was 81.4 months (range 28.1–157.0 months), and recurrence occurred in 48.3% of patients, with a median RFS of 39.8 months (range 15.7–174.7 months). Cause-specific hazard of recurrence showed a first peak 6 months (0.027), and a second peak 24 months (0.021) after surgery. The later the recurrence, the higher the chance of receiving curative intent approaches (p = 0.001). Size >5 cm, multiple tumors, microvascular invasion, and cirrhosis were independent predictors of recurrence showing a cause-specific hazard over time. RFS was associated with death for recurrence (hazard ratio: 0.985, 95% CI: 0.977–0.995; p = 0.002). Conclusions: Patients with MS undergoing LR for HCC have good long-term survival. Recurrence occurs in 48% of patients with a double-peak incidence and time-specific hazards depending on tumor-related factors and underlying disease. The timing of recurrence significantly impacts survival. Surveillance after resection should be adjusted over time depending on risk factors. Impact and implications: Metabolic syndrome (MS) is a growing epidemic and a significant risk factor for the development of hepatocellular carcinoma (HCC). The present study demonstrated that patients who undergo surgical resection for HCC on MS have a good long-term survival and that recurrence occurs in almost half of the cases with a double peak incidence and time-specific hazards depending on tumor-related factors and underlying liver disease. Also, the timing of recurrence significantly impacts survival. Clinicians should therefore adjust follow-up after surgery accordingly, considering timing of recurrence and specific risk factors. Also, the results of the present study might help design future trials on the use of adjuvant therapy following resection.

Volume 15 of AGATHÓN follows on from its predecessors on Innovability©® | Digital Transition and Innovability©® | Ecological Transition, aware of its pressing topicality but also of the scope that the proposal of a threefold key of interpretation suggests. We have clarified the meaning of the term ‘innovability’©®, formerly in use in the economic and social sciences, which is attributed to a renewed driving force for a new paradigm of development that expresses one of the most crucial challenges of our time and the need for a ‘solidary’ convergence between the two inescapable instances of ‘innovation’ and ‘sustainability’, as if they were opposites and contrasts: beyond the term used, in a historical moment characterised by environmental, social and economic emergencies, Humanity promotes one of its prerogatives, the use of the ‘things’ that nature makes available to us to do something other than their primary function (innovation), aware that those resources are not inexhaustible (sustainability). In this context, which must always look forward, we must design our best political and systemic actions to promote the need to innovate by using the Planet’s resources well and consciously. The goals of climate neutrality by 2050 and the reduction of CO2 emissions by 55% (compared to the 1990 level) by 2030 (European Commission, 2019, 2021) pose the European Union, and even more so the rest of the world, with several complex issues, including a significant increase in ‘clean’ energy production from alternative and renewable sources, the reduction of energy poverty, greater security of energy supply and a drastic decrease in dependence on energy imports; at the same time, the aim is to foster modern economic growth decoupled from the use of non-renewable resources, the creation of new jobs, and to generate environmental and health benefits, objectives with inevitable cultural, political, economic, production, technological and social implications to be addressed both within one’s borders and in foreign policy. The energy transition is, therefore, complex and challenging to implement because it involves ‘everything’ and is needed ‘everywhere’ but also because globally, primary energy consumption has been steadily increasing for at least half a century. The theoretical and experimental framework presented in Volume 15 of AGATHÓN demonstrates how energy, ecological and digital transitions can contribute synergistically to achieving the goals of decarbonisation and climate neutrality. The contributions published in the form of essays and research papers appear consistent with the 2022 Strategic Foresight Report (European Commission, 2022) based on the JRC report entitled Towards a Green and Digital Future – Key Requirements for Successful Twin Transitions in the European Union (Muench et alii, 2022) and founded on the fundamental concepts of (a) ‘twin’ transitions, as the key to a sustainable, fair and competitive future; (b) ‘just’ transition, for widespread acceptance of green and digital solutions to mitigate consumption and improve efficiency; (c) ‘integrated approach’ to challenges, to maximise the benefits of synergies and better manage risks. From the published contributions, it emerges the need for a paradigm shift that, on the one hand, is characterised by a ‘sufficiency’ approach (regarding new land occupation and new constructions) and a circular economy (to limit the use of non-renewable resources) capable of exploiting the potential of technologies for the new services made possible by digitisation, and on the other hand, relies on new user awareness of the limits of the Planet, pursuable through ‘soft’ urgent actions that are robust, flexible and easy to implement as they require a lower financial commitment. We assume that community energy renewable energy production from hydrogen and production chains can help mitigate greenhouse gas emissions. In that case, the vast existing real estate heritage is an area in which it is possible to intervene effectively, even where it has a historical and cultural value, using tools such as digital twins or analysis methodologies capable of assessing ex-ante the impacts on the ecosystem and prefigure scenarios for cities, buildings and production processes aimed at sustainable development and compatible with the urgent objectives set for 2030 and 2050. These are some of the strategies, pathways, measures and actions that can take place by exploiting the availability of the substantial financial resources allocated by governments for transitions, stimulating the sensitivity of local administrators and enhancing the skills and transversal competencies of technicians and operators in the sector, but also and above all by raising users’ awareness of the risks posed by climate change, to activate their ‘behavioural’ response to the consumption of energy and non-renewable natural resources.

Design, understood as a modern discipline in its broadest sense, has always been inextricably linked to energy production, availability and accessibility. Every project resulting from human creativity and ingenuity, whether material or immaterial, analogue or digital, depends on it; it is necessary to break free from this atavistic dependence by finding alternative paths that lead us to the energy transition. An increase in human awareness is required to accomplish this and achieve social and environmental equity. In this perspective, this paper, starting with the concepts of ‘mitigation’, ‘sufficiency’, ‘circular economy’ and ‘innovability’, illustrates a number of highly replicable experiments carried out by the multidisciplinary Dotdotdot Studio by employing storytelling, emotive technology and the value of data to generate awareness in users on the issue of energy conservation. Article info Received: 15/05/2024; Revised: 17/05/2024; Accepted: 20/05/2024

The research community has conducted several controlled “in -lab” assessments on the effectiveness of industrial exoskeletons, paving the way for their adoption. However, field testing, focusing on ergonomics and the user experience, could serve to enhance both end-users' awareness and address open doubts concerning true effectiveness of industrial exoskeletons. This study presents an analysis of qualitative data regarding the use of back-support exoskeletons during field trials in harsh civil engineering environments. This work evaluates the StreamEXO's (an active back-support exoskeleton) efficacy in reducing fatigue and the evolution of its perceived usefulness. This is achieved using qualitative data collection tools, during real scenarios testing over multiple-day trials. Collected data shows a positive correlation between self-reported fatigue, measured on a four verbal anchors-based Borg CR10 scale, and the use of the exoskeleton during physically demanding movements. Moreover, the evolution of scores throughout the testing sessions (90 minutes of exoskeleton use for three nonconsecutive days) suggests a trend due to the adaptation and learning curve of workers during the exoskeleton experience. The analysis of the open-ended answers highlights that the adaptation to physical interaction has a negative oscillation on day two to rise back during the third day, possibly correlated to a change in muscle pattern. The main critical factors affecting comfort during the exoskeleton experience are weight balance, body pressure, and thermal comfort, which can strongly affect device acceptance.

Introduction Nodal metastases (LNM) are one of the major determinants of prognosis following surgery for intrahepatic cholangiocarcinoma (ICC). Previous studies investigating the correlation between clinical-radiological features and the probability of LNM include patients undergoing inadequate nodal sampling. Aim of this study was to develop a model to predict the risk of LNM in patients undergoing adequate lymphadenectomy using preoperative clinical and radiological features. Methods Patients undergoing radical surgery for ICC with adequate lymphadenectomy at seven Italian Centers between 2000 and 2023 were collected and divided in a derivation and a validation cohort. Logistic regression and dominance analysis were applied in the derivation cohort to identify variables associated with LNM at pathology. The final coefficients were derived from the model having the highest c-statistic in the derivation cohort with the lowest number of variables included (parsimony). The model was then tested in the external validation cohort and the linear predictor was divided into quartiles to generate four risk categories. Results A total of 693 patients were identified. Preoperative Ca19-9, clinically suspicious lymph nodes at radiology, patients’ age and tumour burden score were significantly associated with LNM. These factors were included in a model (https://aicep.website/?cff-form=20) showing a c-statistic of 0.723 (95%CI: 0.680, 0.766) and 0.771 (95%CI: 0.699, 0.842) in the derivation and validation cohort respectively. A progressive increase of pathological lymph node positivity across risk groups was observed (29.9% in low-risk, 45.1% in intermediate-low risk, 51.5% in intermediate-high risk and 87.3% in high-risk patients; p=0.001). Conclusions A novel model that combines preoperative Ca19-9, clinically suspicious lymph nodes at radiology, patients’ age and tumour burden score was developed to predict the risk of lymph node metastasis (LNM) before surgery. The model exhibited high accuracy, and has the potential to assist clinicians in the management of patients who are candidate to surgery.

Resumo Fundamento: A terapia de reperfusão precoce é reconhecida como a abordagem mais eficaz para reduzir as taxas de letalidade de casos em pacientes com infarto do miocárdio com supradesnivelamento do segmento ST (IAMCSST). Objetivo: Estimar as consequências clínicas e econômicas do atraso da reperfusão em pacientes com IAMCSST. Métodos: O presente estudo de coorte retrospectivo avaliou as taxas de mortalidade e as despesas totais decorrentes do atraso na terapia de reperfusão em 2.622 indivíduos com IAMCSST. Os custos de cuidados hospitalares e perda de produtividade por morte ou incapacidade foram estimados sob a perspectiva do Sistema Único de Saúde indexado em dólares internacionais (Int$) ajustados pela paridade do poder de compra. Foi considerado estatisticamente significativo p < 0,05. Resultados: Cada hora adicional de atraso na terapia de reperfusão foi associada a um aumento de 6,2% (intervalo de confiança de 95%: 0,3% a 11,8%, p = 0,032) no risco de mortalidade hospitalar. As despesas gerais foram 45% maiores entre os indivíduos que receberam tratamento após 9 horas em comparação com aqueles que foram tratados nas primeiras 3 horas, impulsionados principalmente pelos custos hospitalares (p = 0,005). Um modelo de regressão linear multivariada indicou que para cada 3 horas de atraso na trombólise, houve um aumento nos custos hospitalares de Int$ 497 ± 286 (p = 0,003). Conclusões: Os achados do nosso estudo oferecem mais evidências que enfatizam o papel crucial da terapia de reperfusão imediata no salvamento de vidas e na preservação dos recursos de saúde pública. Estes resultados enfatizam a necessidade urgente de implementação de uma rede para gerir casos de IAMCSST.

Background and aims: Cardiomyocyte hypertrophy and interstitial fibrosis are key components of myocardial remodeling in Heart Failure (HF) with preserved (HFpEF) or reduced ejection fraction (HFrEF). MicroRNAs (miRNAs) are non-coding, evolutionarily conserved RNA molecules that may offer novel insights into myocardial remodeling. This study aimed to characterize miRNA expression in HFpEF (LVEF ≥ 45%) and HFrEF (LVEF

Abstract Background The escalating prevalence of type 2 diabetes (T2DM) poses an unparalleled economic catastrophe to developing countries. Cardiovascular diseases remain the primary source of costs among individuals with T2DM, incurring expenses for medications, hospitalizations, and surgical interventions. Compelling evidence suggests that the risk of cardiovascular outcomes can be reduced by three classes of glucose-lowering therapies (GLT), including SGLT2i, GLP-1A, and pioglitazone. However, an evidence-based and cost-effective protocol is still unavailable for many countries. The objective of the current study is to compare the effectiveness and cost-effectiveness of GLT in individuals with T2DM in Brazil. Methods We employed Bayesian Networks to calculate the incremental cost-effectiveness ratios (ICER), expressed in international dollars (Int$) per disease-adjusted life years [DALYs] averted. To determine the effectiveness of GLT, we conducted a systematic review with network meta-analysis (NMA) to provide insights for our model. Additionally, we obtained cardiovascular outcome incidence data from two real-world cohorts comprising 851 and 1337 patients in primary and secondary prevention, respectively. Our cost analysis took into account the perspective of the Brazilian public health system, and all values were converted to Int$. Results In the NMA, SGLT2i [HR: 0.81 (95% CI 0.69–0.96)], GLP-1A [HR: 0.79 (95% CI 0.67–0.94)], and pioglitazone [HR: 0.73 (95% CI 0.59–0.91)] demonstrated reduced relative risks of non-fatal cardiovascular events. In the context of primary prevention, pioglitazone yielded 0.2339 DALYs averted, with an ICER of Int$7,082 (95% CI 4,521–10,770) per DALY averted when compared to standard care. SGLT2i and GLP-1A also increased effectiveness, resulting in 0.261 and 0.259 DALYs averted, respectively, but with higher ICERs of Int$12,061 (95% CI: 7,227–18,121) and Int$29,119 (95% CI: 23,811–35,367) per DALY averted. In the secondary prevention scenario, all three classes of treatments were deemed cost-effective at a maximum willingness-to-pay threshold of Int$26,700. Notably, pioglitazone consistently exhibited the highest probability of being cost-effective in both scenarios. Conclusions In Brazil, pioglitazone presented a higher probability of being cost-effective both in primary and secondary prevention, followed by SGLT2i and GLP-1A. Our findings support the use of cost-effectiveness models to build optimized and hierarchical therapeutic strategy in the management of T2DM. Trial registration CRD42020194415.

Abstract Raspberries (Rubus spp) are temperate climate fruits with profitable high returns and have the potential for diversification of fruit growing in mid to low-latitude regions. However, there are still no cultivars adapted to climatic conditions and high pressure of diseases that occurs in tropical areas. In this context, our objective was to evaluate the genetic diversity from a 116 raspberry genotypes panel obtained from interspecific crosses in a testcross scheme with four cultivars already introduced in Brazil. The panel was genotyped via genotyping-by-sequencing. 28,373 and 27,281 SNPs were obtained, using the species R. occidentalis and R. idaeus genomes as references, respectively. A third marker dataset was constructed consisting of 41,292 non-coincident markers. Overall, there were no differences in the results when using the different marker sets for the subsequent analyses. The mean heterozygosity was 0.54. The average effective population size was 174, indicating great genetic variability. The other analyses revealed that the half-sibling families were structured in three groups. It is concluded that the studied panel has great potential for breeding and further genetic studies. Moreover, only one of the three marker matrices is sufficient for diversity studies.

Couroupita guianensis, a medicinal plant autochthonal to South America and South India, is widely used in the ethnomedicine of the indigenous peoples of these regions thanks to its alleged antimicrobial, anti-inflammatory, antioxidant and wound-healing properties. The majority of studies have mainly analyzed organic extracts of the Indian plant’s flowers and leaves, with limited research on its bark decoction, traditionally used in Amazonian shamanic medicine. In this study, we investigated the anticancer effects of the bark decoction and its main fractions obtained through chromatographic separation, as well as the underlying molecular mechanisms in AGS gastric cancer cells. Viability, cell proliferation, cell cycle, apoptosis and protein expression related to these processes were evaluated. Both the bark decoction and fraction III significantly inhibited cell viability, and the cytotoxic effect was linked to cell cycle blockade and the induction of apoptosis also through an engulfment of the autophagic flux. Increased expression or activation of the key proteins (p53, p21, cdk2, Bak, caspases, pAMPK, pAkt, beclin, p62 and LC3BII) involved in these processes was observed. The results obtained confirmed an important anticancer effect of C. guianensis bark decoction, providing scientific validation for its use in traditional medicine and highlighting its potential as a therapeutic agent against gastric cancer.

Whereas an exercise intervention effectively improves patients’ quality of life, little information is available about the contribution of each physical fitness component. This study aims to explore the association between physical fitness components and the quality-of-life domain in patients with cancer. Between September 2021 and August 2023, 160 patients with mixed cancer types visiting the Oncology Unit were selected on a consecutive basis according to selection criteria. They underwent a comprehensive baseline assessment including the six-minute walking test, the handgrip strength test, the isometric leg press test, the back scratch, sit and reach tests, their waist–hip ratio, and their body mass index. The European Organization for Research and Treatment of Cancer Quality of Life and Core Questionnaire was used to measure the quality of life. The sample size was based on the use of regression models to study associations between clinical characteristics and fitness outcomes. All of the analyses were performed using the SPSS v.25 statistical package. Patients had a mean age of 58 years, 68% were female, 42% were affected by breast cancer, and all were receiving anticancer treatments. Higher functional capacity was associated with better global health status (p < 0.0001) and physical (p < 0.0001), role (p < 0.0001), emotional (p = 0.026), and social function (p = 0.016) and inversely linked with fatigue (p = 0.001). Lower-limb flexibility was significantly associated with all of the domains except for role and social functions. The waist–hip ratio was inversely associated with physical function (p < 0.0001) and positively related to fatigue (p = 0.037). Exercise programs aiming to improve the quality of life in cancer should be addressed to optimize these fitness components.

Glioblastoma (GBM) is one of the most aggressive cancers, characterized by a decrease in antioxidant levels. Evidence has demonstrated that ferulic acid (FA), a natural antioxidant particularly abundant in vegetables and fruits, could be a promising candidate for GBM treatment. Since FA shows a high instability that compromises its therapeutic application, it has been encapsulated into Nanostructured Lipid Carriers (NLCs) to improve its bioavailability in the brain. It has been demonstrated that tissue transglutaminase (TG2) is a multi-functional protein implicated in many physiological and pathological processes, including cancer. TG2 is also involved in GBM correlated with metastasis formation and drug resistance. Therefore, the evaluation of TG2 expression levels and its cellular localization are important to assess the anti-cancer effect of FA against GBM cancer. Our results have demonstrated that treatment with free FA and FA-NLCs in the U87-MG cancer cell line differently modified TG2 localization and expression levels. In the cells treated with free FA, TG2 appeared expressed both in the cytosol and in the nucleus, while the treatment with FA-NLCs showed that the protein is exclusively localized in the cytosol, exerting its pro-apoptotic effect. Therefore, our data suggest that FA loaded in NLCs could represent a promising natural agent for supplementing the current anti-cancer drugs used for the treatment of GBM.