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Abstract Science should drive policies and regulations to ensure a sustainable (environmentally, socially, and economically) green transition to a Net-Zero / Net-Negative circular economy. Since 2015, which saw COP21 in Paris, Net Zero has been a global target that must be rapidly accompanied by a Net Negative strategy to mitigate climate change. Accordingly, biochar's role as a durable carbon removal method is gaining attention and increasing. In this work, we discuss the durability of the carbon in biochar and the need for analytical techniques to support stakeholders on a project level. The different ecologically relevant groups of carbon forms contained in biochar are presented, and possible project-based methods to assess the quality and durability of the product versus the regulatory requirements for the permanence of carbon removals are summarized. Biochar is today one of the CDR technologies with the highest technology readiness level (TRL 8–9) that can ensure permanent removals for time frames relevant to climate change mitigation projects, combined with co-benefits that are gaining relevance in terms of mitigating climate impacts in agricultural soils. Graphical Abstract

Background: This study evaluates the repeatability and reproducibility of fat-fraction percentage (FF%) in whole-body magnetic resonance imaging (WB-MRI) of prostate cancer patients with bone metastatic hormone naive disease. Methods: Patients were selected from the database of a prospective phase-II trial. The treatment response was assessed using the METastasis Reporting and Data System for Prostate (MET-RADS-P). Two operators identified a Small Active Lesion (SAL,

Purpose: The impact of dietary counseling on body composition in early breast cancer patients (EBC) treated with aromatase inhibitors (AIs) is uncertain. The aim of this study was to assess the effects of a diet counseling program on weight, BMI, total and regional body composition in patients treated with AIs. Methods: This observational study involved 194 EBC patients, of which 97 attended a 6-month personalized counseling program, based on Mediterranean diet principles (cohort A) and 97 did not (cohort B). Dual-energy X-ray absorptiometry (DXA) scan was used to measure the total and regional fat and lean body mass, before (baseline) and after at least 18 months of AI-therapy. Results: Weight and BMI increased significantly, on the average, in cohort B, but not in cohort A. In the cohorts A and B, fat mass increased by 10 % and 7.7 % respectively, while lean mass decreased by 3.3 % and 2.6 % from before to after AI therapy, without statistically significant differences between them using the Mann-Whitney test. The changes in body composition were greater in premenopausal than in postmenopausal women at cancer diagnosis. The proportion of patients with sarcopenia, obesity and sarcopenic obesity increased from before to after AI therapy, similarly in both cohorts. Conclusions: Patients treated with AIs reported an increase in fat mass and a decrease in lean mass, and consequently an increase in sarcopenia and obesity, regardless of the participation in a dietary counseling program. A combined dietary counseling and physical exercise program may be necessary for preventing these unfavourable changes in these patients.

The efficacy of adjuvant denosumab in combination with hormonotherapy in breast cancer patients was investigated in two randomized trials, ABCSG-18 and D-Care, but the results were mixed with respect to the impact of this drug on disease-free survival. However, the ABCSG-18 study has achieved its primary goal: prevention of clinical fractures. Therefore, the protective role of Denosumab on bone fragility induced by estrogen deprivation, already demonstrated in post-menopausal women, has been validated in the breast cancer setting.

IntroductionRegorafenib is an oral multi-targeted tyrosine kinase inhibitor (TKI) indicated for the treatment of various tumor types, including metastatic gastrointestinal stromal tumors (GIST), as a third-line systemic therapy. Erythrocytosis, which is characterized by an increase in erythrocyte count, hemoglobin, and hematocrit levels, has been described as a side effect of some antiangiogenic TKIs but has never been associated with regorafenib administration.Case presentationAn extra-GIST was diagnosed in a 58-year-old woman after she underwent surgery to remove a pelvic mass. Three years later, systemic therapy with imatinib was started due to pelvic disease recurrence. However, after six months, due to disease progression, we prescribed sunitinib, which the patient received for four years. Regorafenib was initiated in June 2019, and after six months, we noted an increase in the erythrocytes’ count and hemoglobin (Hb) levels. Given that the patient had clinical benefit and hematocrit was within normal range, we only monitored the blood cell count and continued to give regorafenib at the same dose. The drug was then stopped for over six weeks due to hospitalization for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and Hb levels returned to normal. Therefore, we decided to restart regorafenib at a lower dose. However, Hb levels rose again in conjunction with increased hematocrit, resulting in the need for multiple phlebotomies. We attempted to restart regorafenib every other day, but it was unsuccessful, so we stopped it permanently in May 2023, and all values returned to normal.ConclusionRegorafenib may cause secondary erythrocytosis that could not be dose-related, as this case report suggests. Secondary erythrocytosis might be a marker of TKI efficacy, given the patient’s prolonged clinical benefit during regorafenib treatment (48 months). In patients receiving regorafenib, monitoring blood count as well as any symptoms associated with erythrocytosis may be suggested.

Immune checkpoint inhibitors (ICIs)-based combinations have improved survival outcomes of advanced renal cell carcinoma (RCC) patients and are currently recommended as first-line treatment options. Rheumatoid arthritis (RA) is a systemic autoimmune disease (AD) of unknown etiology characterized by a chronic inflammatory process involving joints and extra-articular organs. Patients with AD are usually excluded from large randomized clinical trials investigating immunotherapeutic drugs. Therefore, little is known about clinical outcomes of patients with a history of RA treated with ICIs in real-world practice. In the present study, we report the clinical outcome of an advanced RCC patient with a history of RA treated with pembrolizumab in combination with axitinib. The patient experienced serious immune-related adverse events (irAEs) and achieved pathological complete response following only one ICI administration. Our case report shows that ICI-based combinations can be administered efficaciously in advanced RCC patients with a history of AD. However, a close monitoring of these patients is required, given the risk of irAEs and clinical exacerbations of symptoms associated with the preexisting AD. Moreover, prospective clinical data are needed to assess the hypothesis of a correlation between the onset of irAEs and AD flares and responses and survival outcomes to ICIs.

Background: Among its extragonadal effects, follicle-stimulating hormone (FSH) has an impact on body composition and bone metabolism. Since androgen deprivation therapy (ADT) has a profound impact on circulating FSH concentrations, this hormone could potentially be implicated in the changes of fat body mass (FBM), lean body mass (LBM), and bone fragility induced by ADT. The objective of this study is to correlate FSH serum levels with body composition parameters, bone mineral density (BMD), and bone turnover markers at baseline conditions and after 12 months of ADT. Methods: Twenty-nine consecutive non-metastatic prostate cancer (PC) patients were enrolled from 2017 to 2019 in a phase IV study. All patients underwent administration of the luteinizing hormone-releasing hormone antagonist degarelix. FBM, LBM, and BMD were evaluated by dual-energy x-ray absorptiometry at baseline and after 12 months of ADT. FSH, alkaline phosphatase, and C-terminal telopeptide of type I collagen were assessed at baseline and after 6 and 12 months. For outcome measurements and statistical analysis, t-test or sign test and Pearson or Spearman tests for continuous variables were used when indicated. Results: At baseline conditions, a weak, non-significant, direct relationship was found between FSH serum levels and FBM at arms (r = 0.36) and legs (r = 0.33). Conversely, a stronger correlation was observed between FSH and total FBM (r = 0.52, p = 0.006), fat mass at arms (r = 0.54, p = 0.004), and fat mass at trunk (r = 0.45, p = 0.018) assessed after 12 months. On the other hand, an inverse relationship between serum FSH and appendicular lean mass index/FBM ratio was observed (r = −0.64, p = 0.001). This is an ancillary study of a prospective trial and this is the main limitation. Conclusions: FSH serum levels after ADT could have an impact on body composition, in particular on FBM. Therefore, FSH could be a promising marker to monitor the risk of sarcopenic obesity and to guide the clinicians in the tailored evaluation of body composition in PC patients undergoing ADT. Funding: This research was partially funded by Ferring Pharmaceuticals. The funder had no role in design and conduct of the study, collection, management, analysis, and interpretation of the data and in preparation, review, or approval of the manuscript. Clinical trial number: clinicalTrials.gov NCT03202381, EudraCT Number 2016-004210-10.

IntroductionCasirivimab and imdevimab (CAS/IMV) are two non-competing, high-affinity human IgG1 anti-SARS-CoV-2 monoclonal antibodies, that showed a survival benefit in seronegative hospitalized patients with COVID-19. This study aimed to estimate the day-28 risk of mechanical ventilation (MV) and death in individuals hospitalized for severe COVID-19 pneumonia and receiving CAS/IMV. Additionally, it aimed to identify variables measured at the time of hospital admission that could predict these outcomes and derive a prediction algorithm.MethodsThis is a retrospective, observational cohort study conducted in 12 hospitals in Italy. Adult patients who were consecutively hospitalized from November 2021 to February 2022 receiving CAS/IMV were included. A multivariable logistic regression model was used to identify predictors of MV or death by day 28 from treatment initiation, and β-coefficients from the model were used to develop a risk score that was derived by means of leave-one-out internal cross-validation (CV), external CV, and calibration. Secondary outcome was mortality.ResultsA total of 480 hospitalized patients in the training set and 157 patients in the test set were included. By day 28, 36 participants (8%) underwent MV and 28 died (6%) for a total of 58 participants (12%) experiencing the composite primary endpoint. In multivariable analysis, four factors [age, PaO2/FiO2 ratio, lactate dehydrogenase (LDH), and platelets] were independently associated with the risk of MV/death and were used to generate the proposed risk score. The accuracy of the score in the area under the curve (AUC) was 0.80 and 0.77 in internal validation and test for the composite endpoint and 0.87 and 0.86 for death, respectively. The model also appeared to be well calibrated with the raw data.ConclusionThe mortality risk reported in our study was lower than that previously reported. Although CAS/IMV is no longer used, our score might help in identifying which patients are not likely to benefit from monoclonal antibodies and may require alternative interventions.