Isolating the Role of Bone Lacunar Morphology on Static and Fatigue Fracture Progression through Numerical Simulations

Currently, the onset of bone damage and the interaction of cracks with the surrounding micro-architecture are still black boxes. With the motivation to address this issue, our research targets isolating lacunar morphological and densitometric effects on crack advancement under both static and cyclic loading conditions by implementing static extended finite element models (XFEM) and fatigue analyses. The effect of lacunar pathological alterations on damage initiation and progression is evaluated; the results indicate that high lacunar density considerably reduces the mechanical strength of the specimens, resulting as the most influencing parameter among the studied ones. Lacunar size has a lower effect on mechanical strength, reducing it by 2%. Additionally, specific lacunar alignments play a key role in deviating the crack path, eventually slowing its progression. This could shed some light on evaluating the effects of lacunar alterations on fracture evolution in the presence of pathologies

Gastrointestinal Toxicity of Antibody Drug Conjugates (ADCs) in Metastatic Breast Cancer: A Pooled Analysis

: Trastuzumab emtansine (T-DM1), sacituzumab govitecan (SG), and trastuzumab deruxtecan (T-DXd) are three ADCs approved for the treatment of metastatic breast cancer (MBC). Since gastrointestinal toxicities have been commonly observed with these drugs in clinical trials, a pooled analysis evaluating gastrointestinal adverse events (AEs) in patients with MBC treated with ADCs in clinical trials was performed. PubMed, Embase, and the Cochrane Library were searched from inception until May 2023 for phase II and III clinical trials reporting frequency and severity of gastrointestinal AEs during treatment with ADCs. Data were retrieved for nausea, vomiting, diarrhea, constipation, and abdominal pain: overall and grade 3-4 toxicity rates according to NCI-CTCAE were collected and expressed as proportions. A pre-specified subgroup analysis according to the agent was also carried out. Fourteen studies, comprising 5608 patients, were included in the analysis. Gastrointestinal AEs were frequently registered with SG and T-DXd. A significantly higher frequency of nausea (65.6% with SG, 75% with T-DXd), vomiting (43.7% with SG, 45% with T-DXd), and diarrhea (59.7% with SG, 29% with T-DXd) was noticed with these ADCs compared to TDM-1. Furthermore, diarrhea was more frequently associated with SG (grade 3 in 7.5% of patients), while constipation and abdominal pain were less common. Gastrointestinal AEs, notably nausea and diarrhea, were frequently reported by MBC patients treated with SG and T-DXd in clinical trials. Since these ADCs are administered continuously until disease progression or occurrence of unbearable AEs, gastrointestinal toxicity may have a negative impact on patient quality of life. Therefore, appropriate management of gastrointestinal AEs is mandatory to ensure treatment efficacy and adherence

Should I give kids money? The role of pocket money on at-risk behaviors in Italian adolescents

Background. Discussion on the impact of pocket money on positive behaviors is still debated. Objective. To investigate the effect of diverse money allowance schemes on risky behaviors (smoking, alcohol, binge drinking, drug use, gambling) during adolescence. Method. 989 students aged 15 from Lombardy (Italy) reported information on money availability in the 2018 wave of the Health Behaviour in School-aged Children study. To analyze the relationship between money availability and risky behaviors we computed odds ratios and 95% confidence intervals through unconditional multiple logistic regression models. Results. Spending more than 10€ weekly was associated with higher likelihood to smoke, binge drink or gamble. Receiving pocket money (rather than receiving money upon request) was related to higher likelihood to engage in risky behaviors. Conclusions. Pocket money may have a negative impact on adolescents, particularly with a substantial amount of money. More research is needed to understand why providing money only if needed may serve as a protective factor against risky behaviors

The Role of Positron Emission Tomography/Computed Tomography (PET/CT) for Staging and Disease Response Assessment in Localized and Locally Advanced Pancreatic Cancer

Pancreatic Cancer (PC) has a poor prognosis, with a 5-year survival rate of only 9%. Even after radical surgical procedures, PC patients have poor survival rates, with a high chance of relapse (70–80%). Imaging is involved in all aspects of the clinical management of PC, including detection and characterization of primary tumors and their resectability, assessment of vascular, perineural and lymphatic invasion and detection of distant metastases. The role of Positron Emission Tomography/Computed Tomography (PET/CT) in detecting PC is still controversial, with the international guidelines not recommending its routine use. However, in resectable PC, PET/CT may play a role in assessing PC stage and grade and potential resectability after neoadjuvant treatment. Quantitative image analysis (radiomics) and new PET/CT radiotracers account for future developments in metabolic imaging and may further improve the relevance of this technique in several aspects of PC. In the present review, the current state of the art and future directions of PET/CT in resectable PC are presented

Treatment de-escalation for HPV+ oropharyngeal cancer: A systematic review and meta-analysis

Human Papillomavirus (HPV) related oropharyngeal carcinoma (OPC) carries a better prognosis compared with HPV-counterparts, thereby pushing the adoption of de-intensification treatment approaches as new strategies to preserve superior oncologic outcomes while minimizing toxicity. We evaluated the effect of treatment de-intensification in terms of overall survival (OS), progression-free survival (PFS), locoregional and distant control (LRC and DM) by selecting prospective or retrospective studies, providing outcome data with reduced intensification versus standard curative treatment in HPV+ OPC patients, with a systematic analysis till September 2020. The primary outcome of interest was OS. Secondary endpoints were PFS, LRC, and DM expressed as HR. A total of 55 studies (from 1393 screened references) were employed for quantitative synthesis for 38 929 patients. Among n = 48 studies with data available, de-intensified treatments reduced OS in HPV+ OPCs (HR = 1.33, 95% CI 1.17-1.52; p < 0.01). In de-escalated treatments, PFS was also decreased (HR = 2.11, 95% CI 1.65-2.69; p < 0.01). Compared with standard treatments, reduced intensity approaches were associated with reduced locoregional and distant disease control (HR = 2.51, 95% CI 1.75-3.59; p < 0.01; and HR = 1.9, 95% CI 1.25-2.9; p < 0.01). Chemoradiation improved survival in a definitive curative setting compared with radiotherapy alone (HR = 1.42, 95% CI 1.16-1.75; p < 0.01). When adjuvant treatments were compared, standard and de-escalation strategies provided similar OS. In conclusion, in patients with HPV+ OPC, de-escalation treatments should not be widely and agnostically adopted in clinical practice, as therein lies a concrete risk of offering a sub-optimal treatment to patients

INVESTIGATION OF BIOFILM FORMATION AND ITS ASSOCIATION WITH BIOFILM ASSOCIATED FACTORS OF FOOD-RELATED METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS STRAINS

Microbial biofilm formed on food contact surfaces can lead to significant hygiene and food safety issues. Both methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA) have the ability to form biofilms on various food industry surfaces (Mirani et al., 2013). The aim of this study, was to investigated the relationship between biofilm associated factors and the ability of food-derived MRSA strains to form biofilm. Twentytwo MRSA strains and 3 reference strains (S.aureus ATCC 35556, S. aureus ATCC 12600 and S. epidermidis ATCC 12228) were tested for the detection of some genetic markers associated to the biofilm production, by PCR (Shopsin et al., 2003; Graber et al., 2009); furthermore, the strains were tested for the biofilm production on polystyrene and stainless steel using a previously described method (Di Ciccio et al., 2015). Majority of MRSA isolates (90%) showed similar distribution of adhesion genes (icaA, icaD, cna, fnbA and fnbB), toxin genes (hla and hlb), and staphylococcal regulators (sarA). Majority of biofilm producers isolates (66.7%) were found to carry agr type III whereas most of (87.5%) of the biofilm negative isolates were found to carry agr type I. All MRSA strains were found icaA, icaD, hla positive and fnbB negative. Biofilm formation was observed in the 27.2% of the isolates, of which two strains formed strong biofilms, two moderate biofilms and two formed weak biofilms. The biofilm formation by MRSA strains occurred preferentially on polystyrene (27.2%) compared to stainless steel (9%). In conclusion, this study underline the ability of some genotypes of food related MRSA strains to form biofilm on surfaces largely used in the food industry and the need of carefully control their spread for preventing food safety concern