Effect of destoned olive cake on the aromatic profile of cows’ milk and dairy products: comparison of two techniques for the headspace aroma profile analysis

The aim of this study, carried out within the NOVOROD project (PSR Campania 2007-2013 Misura 124 HC), was to evaluate the aromatic profile of milk and dairy products of dairy cows supplemented with destoned olive cake (DOC). Two techniques for the headspace aroma profile analysis: the thermal desorption by gas chromatography with a mass selective (GC/MS) detector and the electronic nose were compared. The trial was performed into a dairy cow farm. Ten dairy cows were allotted into two homogenous groups: control and experimental. Animals received the same diet, while in the experimental group the concentrate supplementation (15% dry matter) was replaced with DOC. After two weeks of adaptation, animals were fed with the experimental diet for other 15 days. During the experimental period, the milk was collected and cumulatively processed in Caciotta cheese (a soft cheese, 25 days ripened) and in Semicotto cheese (hard cheese, 3 months ripened) for 13 times for each group. Milk and cheese volatile organic compounds (VOCs) were extracted and concentrated with dynamic headspace method and determined by GC/MS. Statistical analysis of data, expressed in arbitrary units (a.u.=peak area × 10–6) and allotted in compound classes, was carried out by ANOVA. All data collected of VOCs were processed with principal component analysis (PCA). Milk and cheese samples were comparatively analysed with the electronic nose, fitted with a tenmetal oxide sensors electronic device. PCA has been used for the evaluation of the pattern data. Our results show that the use of DOC, as an unconventional feed for livestock, has no effect on the aromatic profile of both milk and dairy products. In fact, no significant differences were found in both milk and dairy products between the two groups using the GC/MS method. Also the discriminating analysis carried out by electronic nose did not show significant differences between the two groups. The two compared techniques seem to lead to the same result

Precision Oncology and Systemic Targeted Therapy in Pseudomyxoma Peritonei

Systemic targeted therapy; Pseudomyxoma PeritoneiTeràpia sistèmica dirigida; Pseudomixoma peritoneiTerapia sistémica dirigida; Pseudomixoma peritonealPurpose: Pseudomyxoma peritonei (PMP) is a rare and poorly understood malignant condition characterized by the accumulation of intra-abdominal mucin produced from peritoneal metastases. Currently, cytoreductive surgery remains the mainstay of treatment but disease recurrence and death after relapse frequently occur in patients with PMP. New therapeutic strategies are therefore urgently needed for these patients. Experimental Design: A total of 120 PMP samples from 50 patients were processed to generate a collection of 50 patient-derived organoid (PDO) and xenograft (PDX) models. Whole exome sequencing, immunohistochemistry analyses, and in vitro and in vivo drug efficacy studies were performed. Results: In this study, we have generated a collection of PMP preclinical models and identified druggable targets, including BRAFV600E, KRASG12C, and KRASG12D, that could also be detected in intra-abdominal mucin biopsies of patients with PMP using droplet digital PCR. Preclinical models preserved the histopathological markers from the original patient sample. The BRAFV600E inhibitor encorafenib reduced cell viability of BRAFV600E PMP-PDO models. Proof-of-concept in vivo experiments showed that a systemic treatment with encorafenib significantly reduced tumor growth and prolonged survival in subcutaneous and orthotopic BRAFV600E-PMP-PDX mouse models. Conclusions: Our study demonstrates for the first time that systemic targeted therapies can effectively control PMP tumors. BRAF signaling pathway inhibition represents a new therapeutic opportunity for patients with BRAFV600E PMP who have a poor prognosis. Importantly, our present data and collection of preclinical models pave the way for evaluating the efficacy of other systemic targeted therapies toward extending the promise of precision oncology to patients with PMP.The Project was funded by the PMPNet Research Project, sustained by an Accelerator Award on a project entitled Pseudomyxoma peritonei: building a European multicentric cohort to accelerate new therapeutic perspectives funded by the AECC (GEACC19004PAL; J. Martínez-Quintanilla, D. Cabot and H.G. Palmer), CRUK (A29365; J. Barriuso and O. Aziz) and AIRC (24285; M. Guaglio and M. Deraco). We thank Javier Carmona for revising the cover letter, and Fundación CELLEX for its institutional support. The graphical abstract and schematic representations were created thanks to the BioRender platform. J. Martínez-Quintanilla was granted by an individual fellowship from EU Marie Sklodowska-Curie actions (704319). H.G. Palmer was granted with a Miguel Servet contract (MSII14/ 00037). VHIO would like to acknowledge the Cellex Foundation for providing research facilities and equipment, the CERCA Programme from the Generalitat de Catalunya, the FERO Foundation, the Centro de Investigación Biomédica en Red Cáncer (CIBERONC) and the Agencia Estatal de Investigación for their support on this research as a Center of Excellence Severo Ochoa (CEX2020- 001024-S/AEI/10.13039/501100011033)

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Defining optimal selection criteria to improve prognosis and avoid futility in surgical resection of colorectal peritoneal metastases.

36 Background: Surgical resection of peritoneal metastases of colorectal cancer (CRC PM) may benefit some patients similar to hepatic metastases. This approach remains controversial in part due to inconsistent selection criteria and reported outcomes. The impact of preoperative clinical characteristics and tumor molecular profiles on survival among surgically treated patients is incompletely understood. The aim of this study was to investigate the relationship between possible predictive variables and survival in a large cohort of patients treated on a standardized clinical pathway and to develop a clinically useful patient selection tool. Methods: This retrospective cohort study utilized the database of the Catalonian peritoneal metastases regional program, established in 2006. The program provides treatment for all PM patients within an autonomous region with a population of 7.5 million and includes a single dedicated high volume surgical unit. We included all adult patients with surgically resected CRC PM. The clinical pathway includes the administration of perioperative (neoadjuvant and adjuvant) systemic chemotherapy and has historically included a dose of heated intraoperative intraperitoneal chemotherapy (HIPEC) at the time of surgery. Demographic and clinical data was analyzed with descriptive statistics. Survival and the associated predictors were analyzed with the Cox proportional hazard model with HRs used to create a predictive nomogram. Results: A total of 538 patients (mean age 59) have been treated with surgery and a complete resection (CC0) was achieved in 94% of cases. Planned preoperative systemic chemotherapy was delivered in 95% of cases, consistent with the clinical pathway. Surgical morbidity was low (urgent reoperation 6.1%, postoperative return to the ICU 2.4%, 30-day readmission 4.3%) as was 30-day mortality (0.4%). After a median follow up of 27.5 months, the median overall survival (OS) was 43.1 months. It varied considerably by subgroup: patients with low peritoneal tumor burden had the highest OS (median 49 months) and those with signet ring cell subtype the lowest (median 19 months). Factors independently associated with survival were: N stage at diagnosis, histological subtype, quantified peritoneal tumor burden (PCI score) and presence of visceral involvement. A selection tool and predictive nomogram were designed incorporating the results of the multivariable analysis. Conclusions: A set of clinical variables can be identified that independently influences patient survival after surgical resection of CRC PM that should be used as selection criteria when considering surgery. With optimized patient selection and treatment within a specialized center, excellent survival and low morbidity can be anticipated following surgery for CRC PM. </jats:p