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Introduction: Radiological response assessment to immune checkpoint inhibitor is challenging due to atypical pattern of response and commonly used RECIST 1.1 criteria do not take into account the kinetics of tumor behavior. Our study aimed at evaluating the tumor growth rate (TGR) in addition to RECIST 1.1 criteria to assess the benefit of immune checkpoint inhibitors (ICIs). Methods: Tumor real volume was calculated with a dedicated computed tomography (CT) software that semi-automatically assess tumor volume. Target lesions were identified according to RECIST 1.1. For each patient, we had 3 measurement of tumor volume. CT-1 was performed 8–12 weeks before ICI start, the CT at baseline for ICI was CT0, while CT + 1 was the first assessment after ICI. We calculated the percentage increase in tumor volume before (TGR1) and after immunotherapy (TGR2). Finally, we compared TGR1 and TGR2. If no progressive disease (PD), the group was disease control (DC). If PD but TGR2 < TGR1, it was called LvPD and if TGR2 ⩾ TGR1, HvPD. Results: A total of 61 patients who received ICIs and 33 treated with chemotherapy (ChT) were included. In ICI group, 18 patients were HvPD, 22 LvPD, 21 DC. Median OS was 4.4 months (95% CI: 2.0–6.8, reference) for HvPD, 7.1 months (95% CI 5.4–8.8) for LvPD, p = 0.018, and 20.9 months (95% CI: 12.5–29.3) for DC, p < 0.001. In ChT group, 7 were categorized as HvPD, 17 as LvPD and 9 as DC. No difference in OS was observed in the ChT group (p = 0.786) Conclusion: In the presence of PD, a decrease in TGR may result in a clinical benefit in patients treated with ICI but not with chemotherapy. Monitoring TGR changes after ICIs administration can help physician in deciding to treat beyond PD.

Granulomatosis with polyangiitis (GPA) is a necrotizing vasculitis of the small and medium-sized vessels which manifests as a multisystemic disease involving the upper and lower respiratory tract and the kidneys. The typical age at diagnosis is between 45 and 60 years of age, and childhood onset is rare. Here, we discuss a case of pediatric GPA presenting with a cavitary lung lesion, sinusitis, and glomerulonephritis. This case report underlines the importance of considering GPA among the differential diagnoses of cavitary lung lesions in the pediatric age, especially in the immunocompetent patient and when associated with multisystemic disease.

Treatment response is usually assessed by the response evaluation criteria in solid tumors (RECIST). These criteria may not be adequate to evaluate the response to immunotherapy, considering the peculiar patterns of response reported with this therapy. With the advent of immunotherapy these criteria have been modified to include the evaluation of the peculiar responses seen with this type of therapy (iRECIST criteria), including pseudoprogressions and hyperprogressions. Tumor growth rate (TGR) is a dynamic evaluation that takes into account the kinetics of response to treatment and may help catch the real efficacy of an immunotherapy approach. We performed a retrospective monocentric study to explore the impact of TGR change after nivolumab administration as the second or later line of treatment in patients with metastatic renal cell carcinoma (RCC). We evaluated 27 patients, divided into three categories: Disease control (DC) if there was no PD; lower velocity PD (LvPD) if disease progressed but the TGR at second assessment (TGR2) was lower than the TGR at first assessment (TGR1); higher velocity PD (HvPD) if TGR2 was higher than TGR1. The median OS for the DC group was 11.0 months (95% CI 5.0–17.0) (reference) vs. (not reached) NR (95% CI NR-NR) for LvPD (HR 0.27; 95% CI 0.06–1.30; p 0.102) vs. NR (95% CI NR–NR) for HvPD (HR 0.23; 95% CI 0.06–0.88; p 0.032). There was no difference between LvPD and DC (HR 1.21; 95% CI 0.20–7.28; p 0.838). In patients with metastatic RCC, the second or later line of nivolumab treatment may lead to a deceleration in TGR resulting in an improved survival outcome similar to that observed in patients experiencing tumor regression. In this subgroup, especially in the presence of a clinical benefit, continuing the treatment beyond progression can be recommended.

Background Elevated energy cost is a hallmark feature of gait in older adults. As such, older adults display a general avoidance of walking which contributes to declining health status and risk of morbidity. Exoskeletons offer a great potential for lowering the energy cost of walking, however their complexity and cost often limit their use. To overcome some of these issues, in the present work we propose a passive wearable assistive device, namely Exoband, that applies a torque to the hip flexors thus reducing the net metabolic power of wearers. Methods Nine participants (age: 62.1 ± 5.6 yr; height: 1.71 ± 0.05 m; weight: 76.3 ± 11.9 kg) walked on a treadmill at a speed of 1.1 m/s with and without the Exoband. Metabolic power was measured by indirect calorimetry and spatio-temporal parameters measured using an optical measurement system. Heart rate and ratings of perceived exertion were recorded during data collection to monitor relative intensity of the walking trials. Results The Exoband was able to provide a consistent torque (~ 0.03–0.05 Nm/kg of peak torque) to the wearers. When walking with the Exoband, participants displayed a lower net metabolic power with respect to free walking (− 3.3 ± 3.0%; p  = 0.02). There were no differences in spatio-temporal parameters or relative intensities when walking with or without the Exoband. Conclusions This study demonstrated that it is possible to reduce metabolic power during walking in older adults with the assistance of a passive device that applies a torque to the hip joint. Wearable, lightweight and low-cost devices such as the Exoband have the potential to make walking less metabolically demanding for older individuals.

In recent years information and communication technologies (ICT) have played a significant role in all aspects of modern society and have impacted socioeconomic development in sectors such as education, administration, business, medical care and agriculture. The benefits of such technologies in agriculture can be appreciated only if farmers use them. In order to predict and evaluate the adoption of these new technological tools, the technology acceptance model (TAM) can be a valid aid. This paper identifies the most commonly used external variables in e-learning, agriculture and virtual reality applications for further validation in an e-learning tool designed for EU farmers and agricultural entrepreneurs. Starting from a literature review of the technology acceptance model, the analysis based on Quality Function Deployment (QFD) shows that computer self-efficacy, individual innovativeness, computer anxiety, perceived enjoyment, social norm, content and system quality, experience and facilitating conditions are the most common determinants addressing technology acceptance. Furthermore, findings evidenced that the external variables have a different impact on the two main beliefs of the TAM Model, Perceived Usefulness (PU) and Perceived Ease of Use (PEOU). This study is expected to bring theoretical support for academics when determining the variables to be included in TAM extensions.

Background A ketogenic diet (KD) is a nutritional approach, usually adopted for weight loss, that restricts daily carbohydrates under 30 g/day. KD showed contradictory results on sport performance, whilst no data are available on team sports. We sought to investigate the influence of a KD on different parameters in semi-professional soccer players. Methods Subjects were randomly assigned to a iso-protein (1.8 g/Kg body weight/day) ketogenic diet (KD) or western diet (WD) for 30 days. Body weight and body composition, resting energy expenditure (REE), respiratory exchange ratio (RER), cross sectional area (CSA) and isometric muscle strength of quadriceps, counter movement jump (CMJ) and yoyo intermittent recovery test time were measured. Results There was a significantly higher decrease of body fat ( p  = 0.0359), visceral adipose tissue (VAT) ( p  = 0.0018), waist circumference ( p  = 0.0185) and extra-cellular water ( p  = 0.0060) in KD compared to WD group. Lean soft tissue, quadriceps muscle area, maximal strength and REE showed no changes in both groups. RER decreased significantly in KD ( p  = 0.0008). Yo-yo intermittent test improved significantly ( p  < 0.0001) in both groups without significant differences between groups. CMJ significantly improved ( p  = 0.0021) only in KD. Conclusions This is the first study investigating the effects of a KD on semi-professional soccer players. In our study KD athletes lost fat mass without any detrimental effects on strength, power and muscle mass. When the goal is a rapid weight reduction in such athletes, the use of a KD should be taken into account. Trial registration registered retrospectively on Clinical Trial registration number NCT04078971 .

Opioids have been shown to induce neuroinflammation and immune cell activation, that might contribute to some of the opioid side effects, such as opioid-induced tolerance and paradoxical hyperalgesia. In this context, TLR4/MD-2 complex has been proposed as an off-target site for opioid action. This study was aimed at investigating the effect of fentanyl on lipopolysaccharide (LPS)-induced TLR4/MD-2 activation in rat primary microglia and human monocyte-derived macrophages (MDM). The effect of fentanyl was first explored by measuring the expression and release of different proinflammatory mediators in primary rat microglia and human MDM by real-time PCR and ELISA. Then, the involvement of TLR4/MD-2 signaling was investigated studying NF-κB activation in HEK293 cells stably transfected with human TLR4, MD-2, and CD14 genes (HEK-Blue hTLR4 cells) and in human MDM. Fentanyl increased mRNA levels, as well as the LPS-induced secretion of proinflammatory mediators in primary microglia and MDM. Two inhibitors of TLR4/MD-2 signaling, namely the oxazoline derivative of -palmitoylethanolamine (PEA-OXA) and CLI-095, blocked the production and release of proinflammatory cytokines by microglia stimulated with LPS and fentanyl, suggesting that TLR4/MD-2 could be the target of the proinflammatory activity of fentanyl. Finally, we showed that fentanyl in combination with LPS activated NF-κB signaling in human MDM and in HEK-Blue hTLR4 cells and this effect was blocked by inhibitors of TLR4/MD-2 complex. These results provide new insight into the mechanism of the proinflammatory activity of fentanyl, which involves the activation of TLR4/MD-2 signaling. Our findings might facilitate the development of novel inhibitors of TLR4/MD-2 signaling to combine with opioid-based analgesics for effective and safe pain management.

ObjectivesThe climate crisis is a leading threat to the well being of children globally. In November 2022, we, International Child Health Group (ICHG), ran an international virtual conference ‘Climate Health is Child Health’ with the objective of providing participants with knowledge, motivation and connections to advocate for climate-friendly practices and policies. We aimed to assess the effectiveness of the meeting in achieving these objectives.MethodsThe conference was attended by over 134 delegates from 26 countries. Most participants were trainees or retired members with 28% of attendees from low and middle income countries. The day consisted of 4 keynote addresses, 2 plenary sessions, 6 parallel workshops and virtual networking opportunities. Participants were asked to complete anonymous pre-event questionnaires at registration and post event questionnaires 4–6 weeks post.ResultsFrom the 101 respondents (75%) to the pre-event questionnaire, most people reported least knowledge on climate anxiety and climate change driven child migration. Conversely, participants described greater knowledge on the effects of air pollution on child health, the connection between climate change and nutrition, and health inequalities.Following the event, 57 participants (42%) provided feedback. Self-reported knowledge of the impact of climate change and its impact on child health increased compared to pre-event questionnaire with 82.5% of participants rating their knowledge as 4 or 5 on a scale of 1 to 5 compared to prior to half rating their understanding of as 1 or 2 prior to the event. Additionally, 80.6% of the participants rated their pre-existing knowledge on the effect of air pollution on child health as 1 to 3; while post-event, 80.7% of the participants reported their understanding as 4 to 5. 82% of respondent reported they had made personal or professional behaviour change as a results of the conference, most commonly by becoming involved in advocacy initiatives.All of the respondents found the meeting to be useful with the praise for diverse range of speakers, relevance of the topic, opportunities for networking, and blend of interactive workshops and lectures. It was noted that greater representation from regions most affected by the climate crisis was needed to effectively address the issue.ConclusionsThere is significant interest amongst child health professionals to combat climate change. Despite low postevent response rate we propose that events such as our conference can both improve knowledge, empower and connect clinicians to better advocate for child health in the context of the climate crisis.

Supporting education and training initiatives has been identified as an effective way to address Sustainable Development Challenges. In this sense, e-learning stands out as one of the most viable alternatives considering its advantages in terms of resources, time management, and geographical location. Understanding the reasons that move users to adopt these technologies is critical for achieving the desired social objectives. The Technology Acceptance Model (TAM) provides valuable guidelines to identify the variables shaping users’ acceptance of innovations. The present study aims to validate a TAM extension designed for FARMER 4.0, an e-learning application in the agricultural sector. Findings suggest that content quality (CQ) is the primary determinant of farmers’ and agricultural entrepreneurs’ perception of the tool’s usefulness (PU). Furthermore, experience (EXP) and self-efficacy (SE) shape potential users’ perceptions about ease of use (PEOU). This study offers helpful insight into the design and development of e-learning applications in the farming sector and provides empirical evidence of TAM’s validity to assess technology acceptance.

Background.Radiopharmaceuticals are not supposed to cause adverse drugs reactions (ADR) because they are administered in very low mass quantity. This thought is also confirmed by the fact that very few adverse events are reported. The new adverse drug reaction definition, defined by pharmacovigilance European law, effective from July 2nd, 2012 (European Union regulation 1235/2010) is “any untoward medical occurrence that may present during treatment with a medicine” and also reported events related to therapeutic errors, abuse, misuse, off-label use, overdosage and professional exposure. The objective is searching for the adverse radiopharmaceutical reactions in official drug summaries and literature in order to highlight the adverse events due to diagnostic and therapeutic radiopharmaceuticals used for prostate cancer.Materials and methods.Radiopharmaceuticals to diagnose and treat prostate cancer have been selected and their Summaries of Product Characteristics, Micromedex and PubMed databases have been consulted. A computer-aided search of the PubMed/MEDLINE database was conducted to find relevant published articles on adverse drug events of radiopharmaceuticals, using selected and specific strings.Results.Until September 2023, references of the following radiopharmaceuticals have been searched: 5 diagnostic registered drugs: [18F]fluorocholine, [18F]fluciclovine, [18F]sodium fluoride, [99mTc]Tc- diphosphonate, gozetotide kit for [68Ga]Ga-PSMA; 3 extemporaneous diagnostic radiopharmaceuticals: [11C]choline, [68Ga]Ga-PSMA11, [18F]PSMA1007; 3 radiopharmaceuticals administered in therapy: [223Ra]chloride, [153Sm]lexidronam, [177Lu]Lu-vipivotide tetraxetan. Adverse events can definitely occur with diagnostic radiopharmaceuticals, although the frequency is quite low. The most common adverse events are skin and subcutaneous tissue disorders, gastrointestinal and administration site conditions. With therapeutic radiopharmaceuticals hematological, cardiac, gastrointestinal ADR have been found. Moreover, infections, metabolic disorders and bone pain occurred. Specifically, [223Ra]chloride caused anaemia and lymphocytopenia in 72-93% of treated patients; [153Sm]Lexidronam thrombocytopenia, myelosuppression and granulocytopenia in 59-69% of patients; [177Lu]Lu-vipivotide tetraxetan anaemia (12,9%), thrombocytopenia (7,9%), lymphopenia (7,8%) e fatigue (5,9%).Conclusions.Studies on ADR result in awareness on the fact that also radiopharmaceuticals can cause adverse events. Thanks to the methodology it has been possible to evaluate the data in Summaries of Characteristics of Products and in literature. Moreover, this work can be one of the first of future projects on active pharmacovigilance to evaluate safety of radiopharmaceuticals used in many patients, with AIFA endorsement.