Spider surgical system versus multiport laparoscopic surgery. Performance comparison on a surgical simulator

BACKGROUND: The rising interest towards minimally invasive surgery has led to the introduction of laparo-endoscopic single site (LESS) surgery as the natural evolution of conventional multiport laparoscopy. However, this new surgical approach is hampered with peculiar technical difficulties. The SPIDER surgical system has been developed in the attempt to overcome some of these challenges. Our study aimed to compare standard laparoscopy and SPIDER technical performance on a surgical simulator, using standardized tasks from the Fundamentals of Laparoscopic Surgery (FLS). METHODS: Twenty participants were divided into two groups based on their surgical laparoscopic experience: 10 PGY1 residents were included in the inexperienced group and 10 laparoscopists in the experienced group. Participants performed the FLS pegboard transfers task and pattern cutting task on a laparoscopic box trainer. Objective task scores and subjective questionnaire rating scales were used to compare conventional laparoscopy and SPIDER surgical system. RESULTS: Both groups performed significantly better in the FLS scores on the standard laparoscopic simulator compared to the SPIDER. Inexperienced group: Task 1 scores (median 252.5 vs. 228.5; p = 0.007); Task 2 scores (median 270.5 vs. 219.0; p = 0.005). Experienced group: Task 1 scores (median 411.5 vs. 309.5; p = 0.005); Task 2 scores (median 418.0 vs. 331.5; p = 0.007). Same aspects were highlighted for the subjective evaluations, except for the inexperienced surgeons who found both devices equivalent in terms of ease of use only in the peg transfer task. CONCLUSIONS: Even though the SPIDER is an innovative and promising device, our study proved that it is more challenging than conventional laparoscopy in a population with different degrees of surgical experience. We presume that a possible way to overcome such challenges could be the development of tailored training programs through simulation methods. This may represent an effective way to deliver training, achieve mastery and skills and prepare surgeons for their future clinical experience

Calibration and performance of the ATLAS Tile Calorimeter during the LHC Run 2

The central hadronic calorimeter of the ATLAS experiment at the Large Hadron Collider (LHC) is a sampling calorimeter made up of steel and scintillating tiles. TileCal is regularly monitored and calibrated by different calibration systems. A description of the different sources and of the results on the calorimeter performance during the LHC Run 2 is present

Wavelet‐Mixed Landmark Survival Models for the Effect of Short‐Term Changes of Potassium in Heart Failure Patients

Statistical methods to study the association between a longitudinal biomarker and the risk of death are very relevant for the long-term care of subjects affected by chronic illnesses, such as potassium in heart failure patients. Particularly in the presence of comorbidities or pharmacological treatments, sudden crises can cause potassium to undergo very abrupt yet transient changes. In the context of the monitoring of potassium, there is a need for a dynamic model that can be used in clinical practice to assess the risk of death related to an observed patient's potassium trajectory. We considered different landmark survival approaches, starting from the simple approach considering the most recent measurement. We then propose a novel method based on wavelet filtering and landmarking to retrieve the prognostic role of past short-term potassium shifts. We argue that while taking into account the smooth changes in the biomarker, short-term changes cannot be overlooked. State-of-the-art dynamic survival models are prone to give more importance to the smooth component of the potassium profiles. However, our findings suggest that it is essential to also take into account recent potassium instability to capture all the relevant prognostic information. The data used comes from over 2000 subjects, with a total of over 80,000 repeated potassium measurements collected through administrative health records. The proposed wavelet landmark method revealed the prognostic role of past short-term changes in potassium. We also performed a simulation study to assess how and when to apply the proposed wavelet-mixed landmark model

Effect of dietary supplementation with rumen-protected amino acids, lysine and methionine, on the performance of Comisana ewes and on the growth of their lambs

The purpose of the study was to evaluate the effect of supplementing the diets ofComisana ewes with rumen protected methionine and lysine (RP-ML) for a durationof 60 days on quantitative–qualitative production of milk, antioxidant parametersof milk and blood, biochemical parameters of blood, and lambs’ growth perfor-mance. Two groups of 15 ewes with equal average body weight were consideredfor the trial. The control group was administered a standard diet (Control, C) andthe experimental group the standard diet supplemented with 1.5% lysine and 1.0%methionine (Treated, T). Results showed that RP-ML supplementation positivelyinfluenced milk yield, fat and protein content, and casein ( p < 0.01). Furthermore,lambs of the T group, compared with those of the C group, showed a 15% highergrowth rate during the suckling period of 42 days. Finally, the total antioxidantcapacity of milk, measured by ferric reducing antioxidant power and 2,20-azino-bis(3-ethylbenzotiazolin-6-sulfonic acid assay, was significantly lower in T groups( p < 0.05). In conclusion, the results showed that the integration of RP-ML in ewescould be a valid strategy in order to improve their performances but further investi-gations are necessary to define the right concentration to be administered to theanimals

Effectiveness of PCSK9 inhibitors: A Target Trial Emulation framework based on Real-World Electronic Health Records

Low-Density Lipoprotein (LDL) cholesterol is one of the main target for cardiovascular (CV) prevention and therapy. In the last years, Proprotein Convertase Subtilisin-Kexin type 9 inhibitors (PCSK9-i) has emerged as a key therapeutic target to lower LDL and were introduced for prevention of CV events. Recently (June 2022) the Italian Medicines Agency (AIFA) modified the eligibility criteria for the use of PCSK9-i. We designed an observational study to estimate the prevalence of eligible subjects and evaluate the effectiveness of PCSK9-i applying a Target Trial Emulation (TTE) approach based on Electronic Health Records (EHR). Subjects meeting the eligibility criteria were identified from July 2017 (when PCSK9-i became available) to December 2020. Outcomes were all-cause death and the first hospitalization. Among eligible subjects, we identified those treated at date of the first prescription. Inverse Probability of Treatment Weights (IPTW) were estimated including demographic and clinical covariates, history of treatment with statins and the month/year eligibility date. Competing risk models on weighted cohorts were used to derive the Average Treatment Effect (ATE) and the Conditional Average Treatment Effect (CATE) in subgroups of interest. Out of 1976 eligible subjects, 161 (8%) received treatment with PCSK9-i. Treated individuals were slightly younger, predominantly male, had more severe CV conditions, and were more often treated with statin compared to the untreated subjects. The latter exhibited a higher prevalence of non-CV comorbidities. A significant absolute and relative risk reduction of death and a lower relative risk for the first hospitalization was observed. The risk reduction for death was confirmed in CATE analysis. PCSk9-i were prescribed to a minority of eligible subjects. Within the TTE framework, the analysis confirmed the association between PCSK9-i and lower risk of events, aligning with findings from randomized clinical trials (RCTs). In our study, PCSK9-i provided protection specifically against all-cause death, expanding upon the evidence from RCTs that had primarily focused on composite CV outcomes

Protein stability regulation in osteosarcoma: the ubiquitin-like modifications and glycosylation as mediators of tumor growth and as targets for therapy

The identification of new therapeutic targets and the development of innovative therapeutic approaches are the most important challenges for osteosarcoma treatment. In fact, despite being relatively rare, recurrence and metastatic potential, particularly to the lungs, make osteosarcoma a deadly form of cancer. In fact, although current treatments, including surgery and chemotherapy, have improved survival rates, the disease's recurrence and metastasis are still unresolved complications. Insights for analyzing the still unclear molecular mechanisms of osteosarcoma development, and for finding new therapeutic targets, may arise from the study of post-translational protein modifications. Indeed, they can influence and alter protein structure, stability and function, and cellular interactions. Among all the post-translational modifications, ubiquitin-like modifications (ubiquitination, deubiquitination, SUMOylation, and NEDDylation), as well as glycosylation, are the most important for regulating protein stability, which is frequently altered in cancers including osteosarcoma. This review summarizes the relevance of ubiquitin-like modifications and glycosylation in osteosarcoma progression, providing an overview of protein stability regulation, as well as highlighting the molecular mediators of these processes in the context of osteosarcoma and their possible targeting for much-needed novel therapy

Flexible Approaches Based on Multistate Models and Microsimulation to Perform Real-World Cost-Effectiveness Analyses: An Application to Proprotein Convertase Subtilisin-Kexin Type 9 Inhibitors

Objectives: This study aims to show the application of flexible statistical methods in real-world cost-effectiveness analyses applied in the cardiovascular field, focusing specifically on the use of proprotein convertase subtilisin-kexin type 9 inhibitors for hyperlipidemia. Methods: The proposed method allowed us to use an electronic health database to emulate a target trial for cost-effectiveness analysis using multistate modeling and microsimulation. We formally established the study design and provided precise definitions of the causal measures of interest while also outlining the assumptions necessary for accurately estimating these measures using the available data. Additionally, we thoroughly considered goodness-of-fit assessments and sensitivity analyses of the decision model, which are crucial to capture the complexity of individuals' healthcare pathway and to enhance the validity of this type of health economic models. Results: In the disease model, the Markov assumption was found to be inadequate, and a "time-reset" timescale was implemented together with the use of a time-dependent variable to incorporate past hospitalization history. Furthermore, the microsimulation decision model demonstrated a satisfying goodness of fit, as evidenced by the consistent results obtained in the short-term horizon compared with a nonmodel-based approach. Notably, proprotein convertase subtilisin-kexin type 9 inhibitors revealed their favorable cost-effectiveness only in the long-term follow-up, with a minimum willingness to pay of 39 000 Euro/life years gained. Conclusions: The approach demonstrated its significant utility in several ways. Unlike nonmodel-based or alternative model-based methods, it enabled to (1) investigate long-term cost-effectiveness comprehensively, (2) use an appropriate disease model that aligns with the specific problem under study, and (3) conduct subgroup-specific cost-effectiveness analyses to gain more targeted insights

MACROCEPHALY FROM A NORMAL VARIANT TO A THREATENING CONDITION. A SINGLE CENTER RETROSPECTIVE STUDY ON 189 SUBJECTS

Introduction: Macrocephaly, defined as a head circumference more than two standard deviations from the normal distribution, is among the most frequently requested neuropediatric consultations. Materials: we conducted a retrospective study on 189 subjects with macrocephaly, from birth to 18 years old, enrolled from October 2001 to December 2019, for diagnostic definition and/or neurodevelopmental assessment. Brain sonography has been performed in all infants and CT or MR in selected patients. Results: macrocephaly was prevalent in males (62.4%), a head circumference >3SD (8.5%) has been associated with a neurodevelopmental impairment. A genetic and/or concomitant malformation were present in 11.1% of the sample. A male prevalence for impaired outcome has been ascertained. Conclusions: early identification of pathological macrocephaly is necessary to plan a possible treatment, an individualized and multidisciplinary follow up and an effective genetic counseling

Understanding Tumor-Stroma Interplays for Targeted Therapies by Armed Mesenchymal Stromal Progenitors: The Mesenkillers.

Tumor represents a complex structure containing malignant cells strictly coupled with a large variety of surroundingcells constituting the tumor stroma (TS). In recent years, the importance of TS for cancer initiation, development,local invasion and metastases became increasingly clear allowing the identification of TS as one of the possibleways to indirectly target tumors. Inside the heterogeneous stromal cell population, tumor associated fibroblasts(TAF) play a crucial role providing both functional and supportive environments. During both tumor and stroma development,several findings suggest that TAF could be recruited from different sources such as locally derived host fibroblasts,via epithelial/endothelial mesenchymal transitions or from circulating pools of fibroblasts deriving form mesenchymalprogenitors, namely mesenchymal stem/stromal cells (MSC). These insights prompted scientists to identifymultimodal approaches to target TS by biomolecules, monoclonal antibodies and, more recently, via cell basedstrategies. These latter appear extremely promising, although associated with still debated and unclear findings. Thisreview discusses on crosstalk between cancers and their stroma, dissecting specific tumor types, such as sarcoma,pancreatic and breast carcinoma where stroma plays distinct paradigmatic roles. The recognition of these distinctstromal functions may help in planning effective and safer approaches aimed either to eradicate or to substitute TSby novel compounds and/or MSC having specific killing activitie