Malliavin-Skorohod calculus and Paley-Wiener integral for covariance singular processes

We develop a stochastic analysis for a Gaussian process $X$ with singular covariance by an intrinsic procedure focusing on several examples such as covariance measure structure processes, bifractional Brownian motion, processes with stationary increments. We introduce some new spaces associated with the self-reproducing kernel space and we define the Paley-Wiener integral of first and second order even when $X$ is only a square integrable process continuous in $L^2$. If $X$ has stationary increments, we provide necessary and sufficient conditions so that its paths belong to the self-reproducing kernel space. We develop Skorohod calculus and its relation with symmetric-Stratonovich type integrals and two types of Itô's formula. One of Skorohod type, which works under very general (even very singular) conditions for the covariance; the second one of symmetric-Stratonovich type, which works, when the covariance is at least as regular as the one of a fractional Brownian motion of Hurst index equal to $H = \frac{1}{4}$

Havep53 gene mutations and protein expression a different biological significance in colorectal cancer?

p53 alterations are considered the most common genetic events in many types of neoplasms, including colorectal carcinoma (CRC). These alterations include mutations of the gene and/or overexpression of the protein. The aim of our study was to assess whether in 160 patients undergoing resective surgery for primary operable CRC there was an association between p53 mutations and protein over-expression and between these and other biological variables, such as cell DNA content (DNA-ploidy) and S-phase fraction (SPF), and the traditional clinicopathological variables. p53 mutations, identified by PCR-SSCP-sequencing analysis, were found in 68/160 patients (43%) and positive staining for p53 protein, detected with the monoclonal antibody DO-7, was present in 48% (77/160) of the cases, with agreement of 57% (91/160). In particular, a significant association was found between increased p53 expression and genetic alterations localized in the conserved regions of the gene or in the L3 DNA-binding domain and the specific type of mutation. Furthermore, both overexpression of p53 and mutations in the conserved areas of the gene were found more frequently in distal than in proximal CRCs, suggesting that they might be "biologically different diseases." Although p53 mutations in conserved areas were associated with flow cytometric variables, overexpression of p53 and mutations in its L3 domain were only related respectively to DNA-aneuploidy and high SPF. These data may reflect the complex involvement of p53 in the different pathways regulating cell-cycle progression. In conclusion, the combination of the mutational status and immunohistochemistry of p53, and flow cytometric data may provide an important insight into the biological features of CRCs

Macrophage Autophagy and Oxidative Stress: An Ultrastructural and Immunoelectron Microscopical Study

The word autophagy broadly refers to the cellular catabolic processes that lead to the removal of damaged cytosolic proteins or cell organelles through lysosomes. Although autophagy is often observed during programmed cell death, it may also serve as a cell survival mechanism. Accumulation of reactive oxygen species within tissues and cells induces various defense mechanisms or programmed cell death. It has been shown that, besides inducing apoptosis, oxidative stress can also induce autophagy. To date, however, the regulation of autophagy in response to oxidative stress remains largely elusive and poorly understood. Therefore, the present study was designed to examine the ratio between oxidative stress and autophagy in macrophages after oxidant exposure (AAPH) and to investigate the ultrastructural localization of beclin-1, a protein essential for autophagy, under basal and stressful conditions. Our data provide evidence that oxidative stress induces autophagy in macrophages. We demonstrate, for the first time by immunoelectron microscopy, the subcellular localization of beclin-1 in autophagic cells

High-Fidelity simulation and its impact on non-technical skills development among healthcare professionals: A systematic review and meta-analysis

Background and aim: High-Fidelity Simulation (HFS) has emerged as a pivotal educational strategy in healthcare, particularly for bridging the gap between theoretical knowledge and practical application. This systematic review and meta-analysis aimed to investigate the efficacy of HFS in enhancing non-technical skills among healthcare professionals. Methods: The literature search was conducted in PubMed, Embase, Scopus, CINAHL, and Google Scholar covering the period from February 2012 to August 2023. The inclusion criteria focused on randomized controlled trials (RCTs) and quasi-experimental studies that assessed the impact of HFS on measurable non-technical skills. Quality assessment was performed using RoB2 for RCTs and ROBINS-I for quasi-experimental studies. A random-effects meta-analysis, sensitivity analysis, and subgroup analyses were conducted. Results: Six studies met the inclusion criteria. The meta-analysis revealed a significant positive impact of HFS on non-technical skills, with an overall effect size (SMD) of 1.433, 95% CI [0.695, 2.172]. However, substantial heterogeneity was observed (I2 = 93.3%). Subgroup analyses indicated variations in effect sizes based on study design, specific non-technical skills domains, and geographic location. Notably, quasi-experimental studies showed a higher effect size compared to RCTs. Conclusions: HFS is an effective educational tool for improving non-technical skills among healthcare professionals, particularly in enhancing self-efficacy. However, the observed heterogeneity and variations in effect sizes underscore the need for more standardized and rigorous research to optimize the use of HFS in different educational and geographical contexts. Future studies should focus on addressing the methodological limitations and exploring the factors contributing to the variability in outcomes. (www.actabiomedica.it

The efficacy of high-fidelity simulation on knowledge and performance in undergraduate nursing students: An umbrella review of systematic reviews and meta-analysis

Objectives: This umbrella review aimed to consolidate the evidence base on the impact of high-fidelity simulation on knowledge and performance among undergraduate nursing students. Design: Umbrella review with meta-analyses of pooled effect sizes, followed by an additional meta-analysis of primary studies from the included systematic reviews, excluding overlapping results. Data sources: Systematic searches were performed up to August 2023 in PubMed, Embase, and Cochrane Library. We included reviews that compared high-fidelity simulation against other learning strategies. Review methods: The risk of bias was assessed for each included systematic review (ROBIS tool) and primary study (RoB 2 or ROBINS-I as appropriate). Random-effect meta-analyses of meta-analyses were performed to estimate the pooled effects of high-fidelity simulation on knowledge and performance. Further random-effect meta-analyses of primary studies were conducted, with overlapping studies excluded (12 %). Subgroup analyses were performed to provide a more comprehensive analysis of the findings. Trim-and-fill analyses were conducted to adjust for potential publication bias. Results: Six systematic reviews were included and encompassed 133 primary studies (2767 and 3231 participants concerning performance and knowledge, respectively). The adjusted pooled effects for knowledge (SMD = 0.877, 95 % CI: 0.182 to 1.572) and performance (SMD = 0.738, 95 % CI: 0.466 to 1.010) closely aligned with those obtained from meta-analyzing the primary studies for knowledge (SMD = 0.980) and performance (SMD = 0.540), both showing high statistical heterogeneity. Traditional lectures represented the more common comparison. The subgroup analysis revealed significant differences in effect sizes across geographic locations, topics, types of control, and how interventions were reported. Conclusions: The results provide robust evidence supporting the integration of high-fidelity simulation into undergraduate nursing programs to enhance students' knowledge and performance. The high reported heterogeneity may be attributed to variations in study contexts or methodologies. Future research should explore the optimal use of high-fidelity simulation in different educational and cultural contexts

One shot NEPA plus dexamethasone to prevent multiple-day chemotherapy in sarcoma patients

Purpose: Chemotherapy-induced nausea and vomiting (CINV) is one of the most feared and disturbing adverse events of cancer treatment associated with decreased adherence to effective chemotherapy regimens. For high-risk soft tissue sarcoma patients, receiving multiple-day chemotherapy (MD-CT), antiemetic guidelines recommend a combination of an NK 1 receptor antagonist (NK 1 -RA), a 5-HT 3 receptor antagonist (5HT 3 -RA), and dexamethasone on each day of the antineoplastic treatment. NEPA is the first oral fixed-dose combination of a highly selective NK 1 -RA, netupitant, and second-generation 5HT 3 -RA, palonosetron. So far, no data has been published in literature about the efficacy of a single dose of NEPA in MD-CT. Methods: We performed a prospective, non-comparative study to assess the efficacy of one shot of NEPA plus dexamethasone in sarcoma patients receiving MD-CT. The primary efficacy endpoint was a complete response (CR: no emesis, no rescue medication) during the overall phase (0–120 h) in cycle 1. The main secondary endpoints were CR during the overall phase of cycles 2 and 3. Results: The primary endpoint was reached in 88.9% of patients. Cycles 2 and 3 overall CR rates were 88.9% and 82.4%, respectively. The antiemetic regimen was well tolerated. Conclusions: This pilot study showed the benefit of one shot of NEPA to prevent CINV in sarcoma patients receiving MD-chemotherapy

A Single-Center, Randomized Controlled Trial to Test the Efficacy of Nurse-Led Motivational Interviewing for Enhancing Self-Care in Adults with Heart Failure

Background: The role of nurse-led motivational interviewing (MI) in improving self-care among patients with heart failure (HF) is promising, even if it still requires further empirical evidence to determine its efficacy. For this reason, this study tested its efficacy in enhancing self-care maintenance (primary endpoint), self-care management, and self-care confidence after three months from enrollment in adults with HF compared to usual care, and assessed changes in self-care over follow-up times (3, 6, 9, and 12 months). Methods: A single-center, randomized, controlled, parallel-group, superiority study with two experimental arms and a control group was performed. Allocation was in a 1:1:1 ratio between intervention groups and control. Results: MI was effective in improving self-care maintenance after three months when it was performed only for patients (arm 1) and for the patients-caregivers dyad (arm 2) (respectively, Cohen's d = 0.92, p-value < 0.001; Cohen's d = 0.68, p-value < 0.001). These effects were stable over the one-year follow-up. No effects were observed concerning self-care management, while MI moderately influenced self-care confidence. Conclusions: This study supported the adoption of nurse-led MI in the clinical management of adults with HF

Novel concepts and strategies in skull base reconstruction after endoscopic endonasal surgery

Recently, a variety of craniofacial approaches has been adopted to enter the skull base, among those, the endonasal endoscopic technique. An effective watertight thereafter: the reconstruction can be performed using different materials, both autologous and non-autologous, individually or combined in a multilayer fashion. The current study was focused on the development of new advanced devices and techniques, aiding in reducing postoperative CSF leak rate. Additive manufacturing allows the design of devices with tailored structural and functional features and, as well, injectable semi-IPNs and composites; therefore specific mechanical/rheological and injectability studies are valuable. Accordingly, we propose new additive-manufactured and injectable devices

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Artificial Intelligence Predictive Models of Response to Cytotoxic Chemotherapy Alone or Combined to Targeted Therapy for Metastatic Colorectal Cancer Patients: A Systematic Review and Meta-Analysis

Simple Summary Metastatic colorectal cancer (mCRC) has high incidence and mortality. Nevertheless, innovative biomarkers have been developed for predicting the response to therapy. We have examined the ability of learning methods to build prognostic and predictive models to predict response to chemotherapy, alone or combined with targeted therapy in mCRC patients, by targeting specific narrative publications. After a literature search, 26 original articles met inclusion and exclusion criteria and were included in the study. We showed that all investigations conducted in this field provided generally promising results in predicting the response to therapy or toxic side-effects, using a meta-analytic approach. We found that radiomics and molecular biomarker signatures were able to discriminate response vs. non-response by correctly identifying up to 99% of mCRC patients who were responders and up to 100% of patients who were non-responders. Our study supports the use of computer science for developing personalized treatment decision processes for mCRC patients. Tailored treatments for metastatic colorectal cancer (mCRC) have not yet completely evolved due to the variety in response to drugs. Therefore, artificial intelligence has been recently used to develop prognostic and predictive models of treatment response (either activity/efficacy or toxicity) to aid in clinical decision making. In this systematic review, we have examined the ability of learning methods to predict response to chemotherapy alone or combined with targeted therapy in mCRC patients by targeting specific narrative publications in Medline up to April 2022 to identify appropriate original scientific articles. After the literature search, 26 original articles met inclusion and exclusion criteria and were included in the study. Our results show that all investigations conducted on this field have provided generally promising results in predicting the response to therapy or toxic side-effects. By a meta-analytic approach we found that the overall weighted means of the area under the receiver operating characteristic (ROC) curve (AUC) were 0.90, 95% C.I. 0.80-0.95 and 0.83, 95% C.I. 0.74-0.89 in training and validation sets, respectively, indicating a good classification performance in discriminating response vs. non-response. The calculation of overall HR indicates that learning models have strong ability to predict improved survival. Lastly, the delta-radiomics and the 74 gene signatures were able to discriminate response vs. non-response by correctly identifying up to 99% of mCRC patients who were responders and up to 100% of patients who were non-responders. Specifically, when we evaluated the predictive models with tests reaching 80% sensitivity (SE) and 90% specificity (SP), the delta radiomics showed an SE of 99% and an SP of 94% in the training set and an SE of 85% and SP of 92 in the test set, whereas for the 74 gene signatures the SE was 97.6% and the SP 100% in the training set