Nerviano Medical Sciences

To date, there is little evidence on laparoscopic repair of peritoneopericardial diaphragmatic hernias (PPDH). The present study reports on surgical technique considerations, complications and outcome. This was a multicentric retrospective cohort study of patients with laparoscopic PPDH repairs, using low-pressure CO2 insufflation (3-4 mmHg) who were operated between October 2022 to November 2024 in two specialist centers. Dog and cat patients were diagnosed with PPDH and treated laparoscopically using low-pressure CO2 insufflation (3-4 mmHg). Patients were either symptomatic or their owners wished for repair. Demographics of patients and details of surgical procedures including follow-up were reported in simple observational statistics. Details of surgical procedures included extent of PPDH, number of ports, insufflation pressure, suture use, use of thoracocentesis with an 18 gauge needle and/or drain, operating and total surgical time, anesthetic and surgical complications during and after surgery and a follow up at 6 months. Twelve canine and one feline patient were included in the study. One case required conversion to open surgery due to CO2-induced pericardial tamponade. All patients survived and had no serious complications. Full laparoscopic repair of PPDH using low insufflation pressure was successfully achieved in 92% (12/13) patients. This is the largest case series to report on outcomes of laparoscopic repairs of PPDH. Laparoscopic treatment of PPDH is a viable option without increased risk of complications.

To evaluate the feasibility, complications and outcomes of thoracoscopic resection of cranial mediastinal masses in cats. Multi-institutional retrospective study. A total of 17 client-owned cats. Data collected from medical records of cats that underwent thoracoscopic surgery for cranial mediastinal masses between January 2019 and December 2024 included signalment, history, clinicopathologic features, preoperative diagnostic imaging and tumor measurement, anesthesiologic and surgical procedures, complications, and short- or long-term follow-ups. The most common clinical sign was dyspnea. All cats started with thoracoscopic surgical exploration. Non-emergent conversion to an open procedure (sternotomy or video-assisted procedures [VATS]) was necessary in six of 17 (35.29%) cats, with conversions primarily occurring in cases with masses larger than 5 cm. The median maximal tumor diameter was 6 cm (range: 2.2-8.1 cm). The most common tumor type was thymoma, identified in 12 of 17 (70.59%) cats. All cats survived the perioperative period and were alive at the short-term follow-up. Mean survival time was 390.62 days. The presence of larger tumor sizes and adhesions were associated with higher conversion rates to open or VATS procedures, underscoring the importance of tumor dimensions in surgical planning. Thoracoscopic surgery for cranial mediastinal masses in cats is technically feasible, with favorable short-24 and long-term outcomes. Conversion rates were lower in cats with smaller masses without adhesions in this study.

CHF6366, a dual action β2-receptor agonist and M3-muscarinic receptor antagonist developed for chronic obstructive pulmonary disease (COPD) was [14C]-radiolabelled on the two different functional moieties of the molecule (either aminobutanolic or carbamate) to characterise its ADME profile following intravenous (IV), intratracheal (IT) and oral (PO) administration. A very low oral bioavailability and a good balance between absorption and lung retention after IT administration were observed, together with a rapid distribution throughout the body and a complete metabolic transformation of the parent drug without relevant gender difference. CHF6366 was observed fully hydrolysed to alcohol (CHF6387) and carboxylic acid (CHF6361) in plasma and urine after IV and IT administration, and mainly unchanged in faeces only after oral administration. An important number of metabolites containing aminobutanolic moiety was excreted via urine, whereas carbamate-containing derivatives were excreted mainly by bile. The major metabolic routes of the alcoholic moiety (CHF6387) included isomerisation (Ma7), conjugation with glucuronic acid and dehydrogenation, while the carboxylic acid moiety (CHF6361) was mainly metabolised through oxidation, glucuronide conjugation and, in both pathways, combinations of those metabolic reactions. No major differences arose also from in vitro metabolism profiles investigated using liver microsomes and hepatocytes of different species.

This work focuses on exploring a new configuration for the reduction of water hardness based on the surface modification of polyurethane (PU) open cell foams by the deposition of thin graphene oxide (GO) washcoat layers. GO was deposited by the dip–squeeze coating procedure and consolidated by thermal treatment. The final washcoat load was controlled by performing consecutive depositions, after three of which, a GO inventory up to 27 wt% was obtained onto PU foams of 60 pores per inch (PPI). The GO-coated PU foams were assembled into a filter, and the performance of the system was tested by continuously feeding water with hardness in the 190–270 mgCa2+,eq·L−1 range. Remarkable results were demonstrated in terms of total adsorbing capacity, which was evaluated by measuring the outlet total hardness by titration and exhibited values up to 63 mgCa2+,eq·gGO−1 at a specific filtered water volume of 650 mLH2O·gGO−1, outperforming the actual state-of-the-art adsorbing capacity of similar GO-based materials.

Cancer cells within a tumour have heterogeneous phenotypes and exhibit dynamic plasticity. How to evaluate such heterogeneity and its impact on outcome and drug response is still unclear. Here, we transcriptionally profile 35,276 individual cells from 32 breast cancer cell lines to yield a single cell atlas. We find high degree of heterogeneity in the expression of biomarkers. We then train a deconvolution algorithm on the atlas to determine cell line composition from bulk gene expression profiles of tumour biopsies, thus enabling cell line-based patient stratification. Finally, we link results from large-scale in vitro drug screening in cell lines to the single cell data to computationally predict drug responses starting from single-cell profiles. We find that transcriptional heterogeneity enables cells with differential drug sensitivity to co-exist in the same population. Our work provides a framework to determine tumour heterogeneity in terms of cell line composition and drug response.

Idiopathic pericarditis (IP) and pericardial mesothelioma (PM) are causes of pericardial effusion in dogs. Pericardiectomy can be a definitive treatment in the case of idiopathic pericardial effusion or a short-term intervention for mesothelioma. The aim of the present study was to investigate which histopathologic parameters are correlated with clinical outcomes in a cohort of dogs that underwent pericardiectomy. The histopathological findings of 22 IPs and 5 PMs were compared with clinical and survival data and the immunohistochemical characterization of immune cells (CD3, CD79α, Iba1). In IP, the mesothelium was lost in 20 cases, reactive in 9, atypical in 3, and mesothelial papillary hyperplasia (MPH) was observed in 4 cases. Numerous macrophages were found in both IPs and PMs especially at the superficial layer of the pericardium. T lymphocytes were observed in mild to moderate numbers and were more numerous than B lymphocytes in both IPs and PMs. MPH was correlated with the quantity of lymphoplasmacytic infiltrate in the superficial layer, inversely related to the thickness of the pericardium, and associated with a longer overall survival. Pericardial fibrosis was present in 19 out of 22 IPs and in all mesotheliomas and was correlated with increased time from initial presentation and pericardiectomy and lymphoplasmacytic infiltrate in the deep zone. Pericardial thickness was correlated with the amount of lymphoplasmacytic and macrophagic infiltrate in the deep zone. Mesothelioma was associated with an increased number of pericardiocentesis procedures before pericardiectomy and with the presence of macrophages in the superficial pericardial layer, edema, fibrin, and hemorrhage. Disease-free interval and overall survival were significantly shorter in patients with mesothelioma compared with IP.

BackgroundRNA-Seq is a well-established technology extensively used for transcriptome profiling, allowing the analysis of coding and non-coding RNA molecules. However, this technology produces a vast amount of data requiring sophisticated computational approaches for their analysis than other traditional technologies such as Real-Time PCR or microarrays, strongly discouraging non-expert users. For this reason, dozens of pipelines have been deployed for the analysis of RNA-Seq data. Although interesting, these present several limitations and their usage require a technical background, which may be uncommon in small research laboratories. Therefore, the application of these technologies in such contexts is still limited and causes a clear bottleneck in knowledge advancement.ResultsMotivated by these considerations, we have developed RNAdetector, a new free cross-platform and user-friendly RNA-Seq data analysis software that can be used locally or in cloud environments through an easy-to-use Graphical User Interface allowing the analysis of coding and non-coding RNAs from RNA-Seq datasets of any sequenced biological species.ConclusionsRNAdetector is a new software that fills an essential gap between the needs of biomedical and research labs to process RNA-Seq data and their common lack of technical background in performing such analysis, which usually relies on outsourcing such steps to third party bioinformatics facilities or using expensive commercial software.