Is Computed-Tomography-Based Body Composition a Reliable Predictor of Chemotherapy-Related Toxicity in Pancreatic Cancer Patients?

BACKGROUND Malnutrition, loss of weight and of skeletal muscle mass are frequent in pancreatic cancer patients, a majority of which will undergo chemotherapy over the course of their disease. Available data suggest a negative prognostic role of these changes in body composition on disease outcomes; however, it is unclear whether tolerance to chemotherapeutic treatment is similarly and/or negatively affected. We aimed to explore this association by retrospectively assessing changes in body composition and chemotherapy-related toxicity in a cohort of advanced pancreatic cancer patients. METHODS Body composition was evaluated through clinical parameters and through radiological assessment of muscle mass, skeletal muscle area, skeletal muscle index and skeletal muscle density; and an assessment of fat distribution by subcutaneous adipose tissue and visceral adipose tissue. We performed descriptive statistics, pre/post chemotherapy comparisons and uni- and multivariate analyses to assess the relation between changes in body composition and toxicity. RESULTS Toxicity risk increased with an increase of skeletal muscle index (OR: 1.03) and body mass index (OR: 1.07), whereas it decreased with an increase in skeletal muscle density (OR: 0.96). Multivariate analyses confirmed a reduction in the risk of toxicity only with an increase in skeletal muscle density (OR: 0.96). CONCLUSIONS This study suggests that the retrospective analysis of changes in body composition is unlikely to be useful to predict toxicity to gemcitabine-nab-paclitaxel

Evaluating the extent and impact of the extreme Storm Gloria on Posidonia oceanica seagrass meadows

Extreme storms can trigger abrupt and often lasting changes in ecosystems by affecting foundational (habitat-forming) species. While the frequency and intensity of extreme events are projected to increase under climate change, its impacts on seagrass ecosystems remain poorly documented. In January 2020, the Spanish Mediterranean coast was hit by Storm Gloria, one of the most devastating recent climate events in terms of intensity and duration. We conducted rapid surveys of 42 Posidonia oceanica meadows across the region to evaluate the extent and type of impact (burial, unburial and uprooting). We investigated the significance of oceanographic (wave impact model), geomorphological (latitude, depth, exposure), and structural (patchiness) factors in predicting impact extent and intensity. The predominant impact of Storm Gloria was shoot unburial. More than half of the surveyed sites revealed recent unburial, with up to 40 cm of sediment removed, affecting over 50 % of the meadow. Burial, although less extensive, was still significant, with 10–80 % of meadow cover being buried under 7 cm of sediment, which is considered a survival threshold for P. oceanica. In addition, we observed evident signs of recently dead matte in some meadows and large amounts of detached drifting shoots on the sea bottom or accumulated as debris on the beaches. Crucially, exposed and patchy meadows were much more vulnerable to the overall impact than sheltered or continuous meadows. Given how slow P. oceanica is able to recover after disturbances, we state that it could take from decades to centuries for it to recoup its losses. Seagrass ecosystems play a vital role as coastal ecological infrastructure. Protecting vulnerable meadows from anthropogenic fragmentation is crucial for ensuring the resilience of these ecosystems in the face of the climate crisis.This study was funded by the CSIC project “Effects of storm Gloria on the western Mediterranean meadows (202030E052) and “Storms of change: as phenomena extreme weather alters Mediterranean coastal ecosystems, their services and their perception by society" (PID2020-113745RB-I00), state program of I+D+I Oriented to the Challenges of the Society and within the framework of the activities of the Spanish Government through the "Maria de Maeztu Centre of Excellence” accreditation to IMEDEA (CSIC-UIB) (CEX2021-001198). We want to thank the SPAS (Society of Fishing and Underwater Activities of Mataró) and the Mataró City Council, which has financed 25 years of the Alguer de Mataró project

Long-Term Response to PD-1 and CTLA-4 Blockade in an SCLC Patient with Negative PD-L1 Expression on Biopsy: A Case Report

Despite recent advances in the availability of new therapeutic agents, small-cell lung cancer (SCLC) remains an aggressive disease with a poor prognosis. While immune checkpoint inhibition has revolutionized the treatment of non-small cell histologies, results in SCLC have shown overall less favorable evolution, and despite initial data from different trials showing potential for development, the lack of reliable biomarkers for patient selection is a major hindrance to their use. Most notably, programmed death-ligand 1 (PD-L1) expression does not appear to play a key role in SCLC responsiveness to immune checkpoint inhibition. While other biomarkers such as tumor mutational burden (TMB) have been suggested to be more relevant, literature data are not univocal on this subject. We report here on a 58-year-old patient with metastatic PD-L1-negative SCLC treated in an advanced and symptomatic setting who obtained a complete and sustained clinical and radiological response to the combination of nivolumab and ipilimumab. We also discuss the impact of treatment-related adverse events, such as autoimmune hypothyroidism, gastroenteric toxicity and pneumonitis, on his quality of life. This case, while it exemplifies the potential of immune checkpoint inhibition in SCLC, highlights the need for a deeper understanding of the mechanisms underlying its efficacy in order to identify patients who are more likely to benefit from treatment

Experimenting with Odour Proficiency Tests Implementation Using Synthetic Bench Loops

Uncertainty in the quantification of odour measurements is a difficult (but needed) task. Critical aspects include panel selection (required by dynamic olfactometry), sampling, and stability of the samples. Proficiency tests (PTs) can help evaluate such contributions; however, the classical approach to PTs, in which laboratories analyse real samples taken from the field, are not as applicable in this field, and are often implemented by only using dry gas cylinders containing stable compounds. Consequently, uncertainties related to the sampling activity cannot be assessed. In particular, high odour levels and the presence of water vapour in emission sources can create significative biases due to sampling techniques used and chemical reactions that can occur before analysis. In this work, we present experimental notes, developed using the experimental facility ‘LOOP’, realised at the RSE research centre in Italy, in order to “help” the definition, in an upgraded protocol for implementing PTs for odour determinations. Using this bench loop is advantageous as it involves the possibility of implementing samples in conditions very similar to reality (i.e., high temperatures, high water content, and the presence of chemical interferents)

A case of atherosclerotic inferior mesenteric artery aneurysm secondary to high flow state

Inferior mesenteric artery aneurysms are very rare and they are among the rarest of visceral artery aneurysms. Sometimes, the distribution of the blood flow due to chronic atherosclerotic occlusion of some arteries can establish an increased flow into a particular supplying district (high flow state). A high flow state in a stenotic inferior mesenteric artery in compensation for a mesenteric occlusive disease can produce a rare form of aneurysm. We report the case of an atherosclerotic inferior mesenteric aneurysm secondary to high flow state (association with occlusion of the celiac trunk and severe stenosis of the superior mesenteric artery), treated by open surgical approach

Research progress on KRAS mutations in colorectal cancer

The RAS gene family, responsible for signal transduction within the mitogen activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PI3K) pathways, is frequently involved in carcinogenesis, and alterations in its member genes can be detected, with variable frequency, in a wide variety of solid and hematological cancers. These alterations may behave as prognostic-predictive biomarkers and driver mutations, making them an interesting therapeutic target. Since their discovery, many strategies have been pursued to act on their signaling pathways. Indeed, in clinical practice, KRAS, the most prominent member of the RAS gene family, represents an especially elusive target in most malignancies; pathway inhibition is carried out upstream, on the EGFR receptor, or downstream, most frequently on the BRAF/MEK/ERK cascade. Recently, clinically relevant direct RAS inhibition has been successfully achieved with the development of potent and selective covalent inhibitors of KRAS c.34G>T (p.G12C). These latest-generation drugs represent both a new and interesting tool in the therapeutic armamentarium and a symbolic end to the myth of KRAS undruggability. However, their clinical relevance and appropriate place in treatment strategies remain to be determined

Molecular Biology and Therapeutic Perspectives for K-Ras Mutant Non-Small Cell Lung Cancers

In non-small cell lung cancer (NSCLC) the most common alterations are identified in the Kirsten rat sarcoma viral oncogene homolog (KRAS) gene, accounting for approximately 30% of cases in Caucasian patients. The majority of mutations are located in exon 2, with the c.34G > T (p.G12C) change being the most prevalent. The clinical relevance of KRAS mutations in NSCLC was not recognized until a few years ago. What is now emerging is a dual key role played by KRAS mutations in the management of NSCLC patients. First, recent data report that KRAS-mutant lung AC patients generally have poorer overall survival (OS). Second, a KRAS inhibitor specifically targeting the c.34G > T (p.G12C) variant, Sotorasib, has been approved by the U.S. Food and Drug Administration (FDA) and by the European Medicines Agency. Another KRAS inhibitor targeting c.34G > T (p.G12C), Adagrasib, is currently being reviewed by the FDA for accelerated approval. From the description of the biology of KRAS-mutant NSCLC, the present review will focus on the clinical aspects of KRAS mutations in NSCLC, in particular on the emerging efficacy data of Sotorasib and other KRAS inhibitors, including mechanisms of resistance. Finally, the interaction between KRAS mutations and immune checkpoint inhibitors will be discussed

On the Synergy between Elemental Carbon and Inorganic Ions in the Determination of the Electrical Conductance Properties of Deposited Aerosols: Implications for Energy Applications

The role of the elemental carbon (EC), in synergy with hygroscopic ionic species, was investigated to study the formation of electrical bridging phenomena once the aerosol deliquescence is achieved. Ambient aerosol samples were collected on hydrophobic surfaces in urban and rural sites in Northern Italy; their conductance was measured in an Aerosol Exposure Chamber (AEC) while varying the relative humidity. An electric signal was detected on 64% of the collected samples with conductance values (11.20 ± 7.43 μS) above the failure threshold (1 μS) of printed circuit boards. The ionic content was higher for non-electrically conductive samples (43.7 ± 5.6%) than for electrically conductive ones (37.1 ± 5.6%). Conversely, EC was two times higher for electrically conductive samples (26.4 ± 4.1 μg cm−2; 8.4 ± 1.7%) than for non-electrical ones (12.0 ± 4.1 μg cm−2; 5.2 ± 1.9%) suggesting that the synergy between the ionic and carbonaceous fractions is necessary to promote a bridging phenomenon. Synthetic aerosols (EC only, saline only, mixed saline and EC) were generated in laboratory and their conductance was measured in the AEC to verify the ambient results. Only in case of a contemporary presence of both EC and ionic components the bridging phenomenon occurred in keeping with the theoretical deliquescence values of each salt (R2 = 0.996)

Neo-Adjuvant Treatment in Primary Resectable Pancreatic Cancer: A Systematic Review and PRISMA-Compliant Updated Metanalysis of Oncological Outcomes

Background: Despite advances in treatment, the prognosis of resectable pancreatic adenocarcinoma remains poor. Neoadjuvant therapy (NAT) has gained great interest in hopes of improving survival. However, the results of available studies based on different treatment approaches, such as chemotherapy and chemoradiotherapy, showed contrasting results. The aim of this systematic review and meta-analysis is to clarify the benefit of NAT compared to upfront surgery (US) in primarily resectable pancreatic adenocarcinoma. Methods: A PRISMA literature review identified 139 studies, of which 15 were finally included in the systematic review and meta-analysis. All data from eligible articles was summarized in a systematic summary and then used for the meta-analysis. Specifically, we used HR for OS and DFS and risk estimates (odds ratios) for the R0 resection rate and the N+ rate. The risk of bias was correctly assessed according to the nature of the studies included. Results: From the pooled HRs, OS for NAT patients was better, with an HR for death of 0.80 (95% CI: 0.72–0.90) at a significance level of less than 1%. In the sub-group analysis, no difference was found between patients treated with chemoradiotherapy or chemotherapy exclusively. The meta-analysis of seven studies that reported DFS for NAT resulted in a pooled HR for progression of 0.66 (95% CI: 0.56–0.79) with a significance level of less than 1%. A significantly lower risk of positive lymph nodes (OR: 0.45; 95% CI: 0.32–0.63) and an improved R0 resection rate (OR: 1.70; 95% CI: 1.23–2.36) were also found in patients treated with NAT, despite high heterogeneity. Conclusions: NAT is associated with improved survival for patients with resectable pancreatic adenocarcinoma; however, the optimal treatment strategy has yet to be defined, and further studies are required