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Contact with animals in oncohaematological children is associated with many benefits, but the risk of contracting zoonosis, even if low, must be taken into consideration. To evaluate awareness on this topic a survey between the Italian paediatric oncohaematology centres was conducted, resulting in heterogeneous responses. The working group of infections and support therapies, the working group of the Italian Association of Paediatric Oncohaematology and the veterinarians of the Italian Veterinary National Federation have drawn up a consent document to unify the indications to be provided to families, with the aim of guaranteeing a safe interaction between patients and animals and improving the collaboration of clinicians with veterinarians and families.

Major associations of medical oncologists remark that novel anticancer treatments should guarantee improvement of survival outcomes as well as of patients' quality of life (QoL). Herein, we investigated QoL assessment and reporting in phase III randomized controlled trials (RCTs) testing new drugs in metastatic non-small cell lung cancer (NSCLC), published between 2010 and 2021. We selected 172 RCTs for further analysis. Only 2/172 (1.2%) trial included QoL among primary study endpoints. Of note, 40/172 (23.3%) trials did not include QoL assessment among endpoints. The majority of RCTs (102/172, 59.3%) did not report QoL results in primary publications. Particularly, RCTs testing immunotherapy, target therapy and chemotherapy did not disclose QoL data in primary publications in 97.0%, 51.5% and 46.5% of cases, respectively. Next, we found that only 43/95 (45.3%) positive studies reported QoL results in primary articles. Of the 102 trials missing QoL data in primary manuscripts, only 21 (20.6%) disclosed QoL results in a secondary publication. Finally, we found a common fail in adherence to CONSORT-PROs items in publications reporting QoL results. In summary, our study reveals a relevant inadequate assessment and under-reporting of QoL in RCTs of novel systemic treatments for patients with metastatic NSCLC.

The Rearranged during Transfection (RET) oncogene has been extensively investigated in solid malignancies, particularly thyroid cancer and non-small cell lung cancer (NSCLC), and represents an attractive therapeutic target. RET rearrangements occur in 1-2% of lung adenocarcinomas, where they function as potent oncogenic drivers. Importantly, tumors harboring RET fusions are particularly sensitive to RET tyrosine kinase inhibitors. Results of the LIBRETTO-001 and ARROW clinical trials led to the approval of novel potent and selective RET inhibitors, selpercatinib and pralsetinib, able to overcome the limits of previously used multikinase inhibitors. Herein, we review the most relevant evidences about the role of RET signaling in NSCLC. In addition, we interrogated the Project GENIE database to investigate common clinical and molecular features of RET-fusion positive NSCLC. This analysis revealed that RET rearrangements occurred more frequently in younger and light smoker patients and were associated with a lower tumor mutational burden, compared to RET-fusion negative tumors. Moreover, we assessed and described the differences between RET genomic alterations in NSCLC and thyroid cancers. Finally, we summarized how the treatment landscape of RET-rearranged NSCLC has changed in the last few years, which are the available data about the recognized mechanisms of resistance to RET inhibitors and the challenges for future development of novel therapeutic strategies, aiming to improve management of patients with RET-fusion positive NSCLC.

Aim: Comparison of first-line FOLFIRINOX (FFN) and nab-paclitaxel plus gemcitabine (NabGem) in patients with metastatic pancreatic ductal adenocarcinoma. Patients & methods: The authors analyzed data from 160 patients with metastatic pancreatic adenocarcinoma receiving first-line FFN (n=43) or NabGem (n=117). Results: FFN and NabGem were similar in median progression-free survival (24.43 vs 26.28weeks; hazard ratio [HR]: 0.88) and medial overall survival (47.43 vs 42.86weeks; HR: 0.90). Of the 43 patients receiving FFN, 26 (60.4%) were treated with second-line NabGem; 14/117 (12.0%) patients receiving NabGem received second-line FFN (p&nbsp

Background: CDK4/6 inhibitors have been approved in combination with endocrine therapy for the treatment of estrogen receptor positive (ER+) metastatic breast cancer. The goal of this study was to discover mechanisms of resistance to ER antagonists alone and in combination with CDK4/6 inhibitors. Results: p21-activated kinase 1 (PAK1) is a serine/threonine kinase amplified in several human cancer types. Specifically, the survey of TCGA for copy number alterations and/or expression showed PAK1 amplification and/or overexpression in ~23% of ER+ breast cancer. To test the hypothesis that PAK1-amplification is related to CDK4/6 inhibitors resistance, we generated two ER+ breast cancer cell lines T47D (harbouring PAK1 amplification) and MCF7 (non PAK1-amplified) resistant to the combination of fulvestrant (ER downregulator) and abemaciclib (CDK4/6 inhibitor), namely T47DFAR and MCF7FAR. T47DFAR and MCF7FAR were obtained, exposing the parental cells to increasing doses of drugs. Interestingly, only the T47DFAR but not the MCF7FAR showed higher level of PAK1 expression and activation compared to the parental cell line. PAK1 pathway activation was evaluated measuring by immunoblot the levels of phosphorylation of PAK1, MEK, ERK and Beta-Catenin. Moreover, the genomic knockdown of PAK1 through RNAi causes a decrease in cell proliferation of T47DFAR, but not of MCF7FAR and parental cells, suggesting the role of PAK1 as a possible mediator of drug resistance. Conversely, overexpression of PAK1 in MCF7 and T47D parental cells was able to generate resistance to the drug combination. PAK-1 has shown to have a different role in the cytosol as pathways mediator and in the nucleus as transcriptional factor. Our data obtained by subcellular fractionation showed that after treatment with fulvestrant-abemaciclib, PAK1 protein accumulates into the cytosol in T47D-FAR compared to parental T47D, probably mediating an enhancement in cytoplasmatic cell signalling and pathway activation. To univocally demonstrate that PAK1 mediates tumor resistance to fulvestrant-abemaciclib combination, we are generating data from RNA-Seq and whole exome sequencing from T47DFAR and MCF7FAR and the relative parental cell lines. Also, we will assess the efficacy of PAK pharmacological inhibition in overcoming such resistance. Conclusions: In conclusion, our data suggest the role of PAK1 as a novel therapeutic target in ER+/PAK1-amplified breast cancer model resistant to endocrine therapy and CDK4/6 inhibitors. Citation Format: Stefania Belli, Alberto Servetto, Concetta Di Mauro, Daniela Esposito, Ada Pesapane, Fabiana Napolitano, Antonio Santaniello, Pietro De Placido, Priscilla Cascetta, Annachiara Carratù, Eleonora Mozzillo, Roberta Marciano, Roberto Bianco, Luigi Formisano. Pak1 as a novel mediator of resistance to endocrine therapy and CDK4/6 inhibitors in ER+/PAK-1amplified breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-06-08.

We systematically reviewed QoL assessment and reporting in RCTs of immune checkpoint inhibitors (ICIs) in solid cancers published between 2013 and 2021. None of the 106 eligible trials included QoL among primary endpoints. QoL results were non-disclosed in 83/106 (78.3%) primary publications. QoL assessment was disclosed exclusively in study protocol and not in methods of the manuscript in 48.5% of publications. In 27.8% of articles, QoL assessment was disclosed in the methods but non-reported among the results. Only in 44.3% of trials missing QoL results in primary manuscripts, QoL data were reported in a secondary publication. A relevant delay occurred in secondary publications, with a median time to secondary articles with QoL results of 33.6 months. Our analysis revealed a significant underreporting of QoL in RCTs of ICIs in solid cancers. Altogether, absent or delayed disclosure of QoL results affect a complete evaluation of clinical benefit of new anticancer treatments.

Background: Immune-checkpoint inhibitors (ICIs) have increased and improved the treatment options for patients with non-oncogene-addicted advanced stage non-small cell lung cancer (NSCLC). However, the role of ICIs in oncogene-addicted advanced stage NSCLC patients is still debated. In this study, in an attempt to fill in the informational gap on the effect of ICIs on other driver mutations, we set out to provide a molecular landscape of clinically relevant oncogenic drivers in programmed death-ligand 1 (PD-L1) positive NSCLC patients. Methods: We retrospectively reviewed data on 167 advanced stage NSCLC PD-L1 positive patients (≥1%) who were referred to our clinic for molecular evaluation of five driver oncogenes, namely, EGFR, KRAS, BRAF, ALK and ROS1. Results: Interestingly, n = 93 (55.7%) patients showed at least one genomic alteration within the tested genes. Furthermore, analyzing a subset of patients with PD-L1 tumor proportion score (TPS) ≥ 50% and concomitant gene alterations (n = 8), we found that n = 3 (37.5%) of these patients feature clinical benefit with ICIs administration, despite the presence of a concomitant KRAS gene alteration. Conclusions: In this study, we provide a molecular landscape of clinically relevant biomarkers in NSCLC PD-L1 positive patients, along with data evidencing the clinical benefit of ICIs in patient NSCLC PD-L1 positive alterations.

Contact with animals in pediatric oncohematologic patients is associated with many benefits, but the risk of contracting zoonoses, even if low, must be considered by clinicians. In order to assess the awareness about this topic, we surveyed the Italian pediatric oncohematology centers, which resulted in heterogeneous responses. The Infectious Diseases Working Group and the Nurse Working Group of the Italian Association of Pediatric Hematology-Oncology, together with veterinarians from the National Federation of Italian Veterinarians, drew up a consensus document to unify the indications to be given to families with the aim of guaranteeing a safe interaction between patients and animals and improving the collaboration of clinicians with veterinarians and families.

The involvement of animals for therapeutic purposes has very ancient roots. To date, it is clear that animal-assisted interventions (AAIs), in addition to ensuring the replacement of missing or deficient affects, improves psychophysiological parameters connected to human health. However, AAI could potentially present risks related to the transmission of infectious agents from animals to humans. Among these microorganisms, E. cuniculi is a microspore which induces pathological effects (fever, headache, nausea, vomiting, diarrhea, breathlessness, respiratory symptoms, and weakness) in both humans and animals. Consequently, an accurate and fast diagnosis of E. cuniculi infection, as well as the identification of new diagnostic approaches, is of fundamental importance. This literature review was carried out to provide an extensive and comprehensive analysis of the most recent diagnostic techniques to prevent and care for E. cuniculi-associated risks in the AAI field.

Patients with locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC) do not present distant metastases but are not eligible for surgery upfront. Chemotherapy regimens, such as FOLFIRINOX (FFN) or nab-paclitaxel plus gemcitabine (GemNab) in combination with loco-regional treatments are generally used in this setting. However, the best treatment choice is unknown. We retrospectively analyzed the information of 225 patients with stage II–III PDAC treated at our institution between October 2011 and December 2020. A total of 94 patients with LA PDAC who are non-eligible for surgery upfront received neoadjuvant FFN or GemNab. Of the 67 patients receiving FFN, 28 (41.8%) underwent surgery after neoadjuvant therapy. Of the 27 patients treated with GemNab, 6 (22.2%) became eligible for resection. The median overall survival (OS) was 85.1 weeks and 54.3 weeks in the FFN and GemNab groups, respectively (HR = 0.54, p = 0.0109). The median OS was 189.7 weeks and 76.4 weeks in the resected and unresected cohorts, respectively (HR = 0.25, p &lt, 0.0001). Neutropenia (37.3%), anemia (6.0%), and diarrhea (6.0%) in the FFN group and neutropenia (22.2%) and thrombocytopenia (18.5%) in the GemNab groups were the most frequent grade 3–4 side effects. Higher rates of thrombocytosis (p &lt, 0.0001) and peripheral edema (p &lt, 0.0001) were observed in the GemNab group. Our results suggest that the use of FFN is associated with more favorable clinical outcomes than GemNab for patients with LA PDAC. Future randomized and controlled clinical trials are needed to further elucidate the role of these regimens and loco-regional treatments in this setting.

Simple Summary Animal-assisted therapies (AATs), as discussed in this review, are structured interventions, involving pets, for patients suffering from different diseases. Although many studies have highlighted the beneficial effects of these interventions on the well-being and health of the humans given the dogs, there are few studies that highlight the involved dogs themselves. Therefore, in this study, we carried out a systematic review to investigate the characteristics of the dogs involved in AATs. Based on the results, in most papers, there is a lack of general information on the dog(s) involved, including the methods used to choose and train the dog and the animal’s health status. These results highlight the need for standardized, specific methods to choose and train the dog and also suggest the need for univocal health protocols to ensure the animal’s welfare, as well as the final results of the therapeutic intervention. Abstract Dogs are considered the most important species involved in animal-assisted therapy (AAT), and the scientific literature focuses on the benefits linked to the involvement of dogs in various therapeutic areas. In this study, we carried out a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, exploring the scientific literature from the last 5 years (2016–2021) on three databases (PubMed, Scopus, and Web of Science) to highlight the characteristics of the dogs involved in AATs. Based on the scientific literature relevant to such dogs, we considered different parameters (i.e., number, age, sex, breed, temperament, methods of choice and training, health status, research goals, and activities with dogs) to include studies in our paper. After screening 4331 papers identified on the searched databases, we selected 38 articles that met the inclusion criteria. Analysis of the included articles showed that the characteristics of the dogs were neglected. Our findings indicated a lack of information about the dogs, as well as the absence of standardized and univocal criteria for dog selection, training programs, and health protocols.

This study was conducted to evaluate the presence of Campylobacter (C.) jejuni and C. coli in dogs at five dog training centers in Southern Italy. A total of 550 animals were sampled by collecting rectal swabs. The samples were processed to detect thermotolerant Campylobacter spp. by culture and molecular methods. Campylobacter spp. were isolated from 135/550 (24.5–95% confidence interval) dogs. A total of 84 C. jejuni (62.2%) and 51 C. coli (37.8%) isolates were identified using conventional PCR. The dog data (age, sex, breed, and eating habits) were examined by two statistical analyses using the C. jejuni and C. coli status (positive or negative) as dependent variables. Dogs fed home-cooked food showed a higher risk of being positive for C. jejuni than dogs fed dry or canned meat for dogs (50.0%, p &lt, 0.01). Moreover, purebred dogs had a significantly higher risk than crossbred dogs for C. coli positivity (16.4%, 0.01). This is the first study on the prevalence of C. jejuni and C. coli in dogs frequenting dog training centers for animal-assisted therapies (AATs). Our findings emphasize the potential zoonotic risk for patients and users involved in AATs settings and highlight the need to carry out ad hoc health checks and to pay attention to the choice of the dog, as well as eating habits, in order to minimize the risk of infection.

Animal-assisted therapy (AAT) is a non-pharmacological therapy aimed at people with physical and/or mental disabilities. Therefore, it is necessary to carry out interventions that guarantee its benefits for patients while also avoiding the risk of zoonoses due to contact with the animals or their mucous membranes. The present study aimed to detect the occurrence of Pasteurella multocida in the oral cavity of dogs attending a &ldquo, dog educational centre&rdquo, and training for AAT interventions. In addition, some of the potential predictable factors of infection (i.e., age, sex, breed, and living conditions) were analyzed. In total, 25/200 dogs examined (12.5%, 95% confidence interval = 8.4&ndash, 18.1%) were positive for P. multocida, as confirmed by PCR. Sex, breed, and living conditions were risk factors associated with P. multocida as revealed by the logistic regression analysis. Specifically, cross-bred female dogs living prevalently outdoors were significantly associated with the presence of P. multocida (p &lt, 0.05). This study represents the first epidemiological survey of the prevalence of P. multocida in the oral cavity of dogs involved subsequently in AAT interventions, highlighting the potential risk of P. multocida infection in patients, often belonging to risk categories (e.g., children, the elderly, and immunocompromised individuals). Therefore, healthcare guidelines could be suggested to integrate the current literature related to the health check of dogs involved in AAT. In this way, it could be ensured that, even with bodily contact during AAT, the risk of pathogen transmission by the co-therapist dog can be avoided.

Recently, many efforts have been made to assess the effectiveness of non-pharmacological therapies as an alternative or supportive option to conventional approaches. Specifically, animal-assisted therapy (AAT) has recently raised a great interest and large research efforts. This work represents a retrospective study carried out over seven years (from 2012 to 2019) in 127 patients with mild-to-moderate Alzheimer&rsquo, s disease. The patients were divided into three groups: an experimental group that received AAT interventions adapted to the formal reality orientation therapy (ROT), a group receiving a formal ROT, and a control group that did not perform any of the previous therapies. All sessions, for all patient groups, were held weekly for a total period of six months. The evaluation of cognitive function was performed through the Mini Mental State Examination (MMSE), while the Geriatric Depression Scale (GDS) assessed the depressive state. Test administration to all patients was performed before the start of the first session (T0) and after the last session (T1). The results obtained showed an improvement in the values in the GDS and MMSE tests. The variations between the average MMSE values between T1 and T0 were 0.94 &plusmn, 0.9 (SD), 0.15 &plusmn, 0.62, and &minus, 0.42 &plusmn, 0.45 in the AAT group, ROT group, and control (CTRL) group, respectively. The variations between the average GDS values between T1 and T0 were &minus, 1.12 &plusmn, 1.17 (SD), &minus, 1.21, and 0.12 &plusmn, 0.66 in the AAT group, ROT group, and CTRL group, respectively. Based on our findings, we can therefore affirm how the study carried out confirms the potential of AAT performed by Federico II Model of Healthcare Zooanthropology, and particularly its efficacy in the treatment of cognitive deficits deriving from Alzheimer&rsquo, s disease.

Animal-assisted interventions are widely implemented in different contexts worldwide. Particularly, animal-assisted therapies and animal-assisted activities are often implemented in hospitals, rehabilitation centers, and other health facilities. These interventions bring several benefits to patients but can also expose them to the risk of infection with potentially zoonotic agents. The dog is the main animal species involved used in these interventions. Therefore, we aimed at collecting data regarding the occurrence of the pathogens ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) in dogs, in order to draft guidelines concerning the possible monitoring of dogs involved in animal-assisted therapies and animal-assisted activities in healthcare facilities. We performed a literature search using the PRISMA guidelines to examine three databases: PubMed, Web of Science, and Scopus. Out of 2604 records found, 52 papers were identified as eligible for inclusion in the review/meta-analysis. Sixteen papers reported data on E. faecium; 16 on S. aureus; nine on K. pneumoniae; four on A. baumannii; eight on P. aeruginosa; and six on Enterobacter spp. This work will contribute to increased awareness to the potential zoonotic risks posed by the involvement of dogs in animal-assisted therapies, and animal-assisted activities in healthcare facilities.

Simple Summary Animal-assisted interventions (AAIs) include a wide range of activities aimed at improving the health and well-being of people with the help of pets. Although there have been many studies on the effects of these interventions on animal and human wellbeing and health, univocal data on the methodological aspects, regarding type and duration of intervention, operators, involved animal species, and so on, are still lacking. In this regard, several systematic reviews in the scientific literature have already explored and outlined some methodological aspects of animal-assisted interventions. Therefore, we developed an umbrella review (UR) which summarizes the data of a set of suitable systematic reviews (SRs), in order to clarify how these Interventions are carried out. From our results, it is shown that there is a widespread heterogeneity in the scientific literature concerning the study and implementation of these interventions. These results highlight the need for the development and, consequently, the diffusion of protocols (not only operational, but also research approaches) providing for a univocal use of globally recognized terminologies and facilitating comparison between the numerous experiences carried out and reported in the field. Abstract Recently, animal-assisted interventions (AAIs), which are defined as psychological, educational, and rehabilitation support activities, have become widespread in different contexts. For many years, they have been a subject of interest in the international scientific community and are at the center of an important discussion regarding their effectiveness and the most appropriate practices for their realization. We carried out an umbrella review (UR) of systematic reviews (SRs), created for the purpose of exploring the literature and aimed at deepening the terminological and methodological aspects of AAIs. It is created by exploring the online databases PubMed, Google Scholar, and Cochrane Library. The SRs present in the high-impact indexed search engines Web of Sciences and Scopus are selected. After screening, we selected 15 SRs that met the inclusion criteria. All papers complained of the poor quality of AAIs; some considered articles containing interventions that did not always correspond to the terminology they have explored and whose operating practices were not always comparable. This stresses the need for the development and consequent diffusion of not only operational protocols, but also research protocols which provide for the homogeneous use of universally recognized terminologies, thus facilitating the study, deepening, and comparison between the numerous experiences described.

Background: Pancreatic adenocarcinoma is the fourth leading cause of cancer-related death. In cases with metastasis, the combination of 5-fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) or gemcitabine-based chemotherapy regimens are considered the standard of care. However, the optimal sequence of these regimens is unclear. Methods: This retrospective study initially evaluated 186 patients with locally advanced/metastatic pancreatic cancer at three Italian institutions between February 2013 and October 2019. All patients had progressed after receiving gemcitabine-based first-line chemotherapy and were subsequently offered second-line FOLFIRINOX, FOLFOX-6, or FOLFIRI treatment. This study evaluated progression-free survival (PFS), overall survival from the start of second-line treatment (OS2), overall survival from the start of first-line treatment (OS1), and safety outcomes. Results: A total of 77 patients received ⩾4 cycles of second-line chemotherapy and were considered eligible: 15 patients received FOLFIRINOX, 32 patients received FOLFOX-6, and 30 patients received FOLFIRI. The FOLFIRINOX group had median PFS of 26.29 weeks and median OS2 of 47.86 weeks, while the FOLFIRI group had median PFS of 10.57 weeks and median OS2 of 25.00 weeks ( p = 0.038). No significant differences were observed between the FOLFIRINOX and FOLFOX-6 groups in terms of PFS (26.29 weeks versus 23.07 weeks) or OS2 (47.86 weeks versus 42.00 weeks). The most common grade 3–4 toxicities were anemia, neutropenia, and thrombocytopenia, which occurred more frequently in the FOLFIRINOX and FOLFOX-6 groups. Conclusion: Relative to the FOLFIRI regimen, the FOLFIRINOX regimen had a favorable toxicity profile and better survival outcomes. No significant differences were observed relative to the FOLFOX-6 regimen.

Authors present a literature review about Animal-Assisted Interventions (AAI) in health care context and aimed to children. They are considered as valid auxiliary therapies, useful to support initiatives in medical, psychological and rehabilitation field. Despite their widespread use, they are discussed in an international scientific debate about best practices for structuring this clinical setting. In this review, 14 original articles, containing empirical data and published in international journals were included. In them, HAI is described as a promoter for processes of decoding, control and use of the emotions, and for promotion of relational skills. Nevertheless, there are few indications about criteria for the choices about operating protocols, professionals included and involved pets. Further studies, highlighting how the declination of HAI in clinical settings can facilitate the achievement of therapeutic goals, are required.

In the last few years, the treatment strategy in Non-Small Cell Lung Cancer (NSCLC) patients has been heavily modified by the introduction of the immune-checkpoint inhibitors. Anti-programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) therapy has improved both progression-free and the overall survival in almost all subgroups of patients, with or without PDL1 expression, with different degrees of responses. However, there are patients that are not benefitting from this treatment. A defined group of immune-checkpoint inhibitors non-responder tumours carry EGFR (epidermal growth factor receptor) mutations: nowadays, anti-PD-1/PD-L1 clinical trials often do not involve this type of patient and the use of immune-checkpoint inhibitors are under evaluation in this setting. Our review aims to elucidate the mechanisms underlying this resistance: we focused on evaluating the role of the tumour microenvironment, including infiltrating cells, cytokines, secreted factors, and angiogenesis, and its interaction with the tumour tissue. Finally, we analysed the possible role of immunotherapy in EGFR mutated tumours.

Stress-related hormones represent relevant factors contributing to the progression of neurodegenerative disorders. This study was aimed to verify whether Animal-Assisted Therapy (AAT) adapted to Reality Orientation Therapy (ROT) could modify salivary cortisol levels in Alzheimer’s patients. Our study was carried out at the Alzheimer’s Daycare Centre in Naples. A sample, homogeneous in age, sex, cultural level, MMSE of 22 patients were divided into two groups: the AAT group, made up of 11 patients that received a cycle of AAT (with dog) adapted to ROT, and the control group (CTRL group), with 11 patients participating in ROT-based activities without the dog. The ROT cycle consisted of 12 meetings, each of which was 45-minutes long. Before and after each meeting, salivary samples were collected for all patients in the respective groups. Cortisol levels were measured by chemiluminescence-based procedures. The MMSE and GDS tests were administered at the start (T0) and the end (T1) of the entire cycle of 12 meetings. The variation of cortisol was evaluated through the General Linear Logistic Model with Mixed Effects (GLLM-ME). Differences in MMSE and GDS were evaluated using the non-parametric Wilcoxon test for paired data. The GLM-ME prediction reported the proportion of subjects from the two groups that showed a reduction in cortisol level. An increasing trend was observed for the AAT group while the CTRL group remains confined around the 0.5 value. The Wilcoxon test was significant (P

Background: Animal-assisted intervention (AAIs) represent an adequate expression of integrated medicine, according to the One Health approach. We argue that AAIs are interventions based on interspecific relationships between humans and animals. Although there are many studies on the effects of AAIs on animal and human health and wellbeing, research is still needed to give us more data. For example, information is still lacking on the aspects characterizing and influencing the interspecific relationships occurring in AAIs. The efficacy of an intervention based on interspecific relationships will be influenced by different factors, such as attachment styles and personalities of both the animal and the handler, an appropriate choice of animal species and their individuality, animal educational training techniques, the relationship between the handler and the animal, and relational reciprocity between animal, the patients, and members of the working team. Method: This article aims to contribute to the study of interspecific relationships in AAIs via theoretical considerations. An interspecific relationship determines the result of safe interventions, which directly influences the welfare of the animal. Results and considerations: AAIs should be evaluated systemically as a network within a process in which every component interacts with and influences other components. Standardized methods using appropriate tests and parameters are needed to better select appropriate animals (i.e., species and individual subjects) using interspecific relational competences as well as appropriate educational training methods and health protocols to assess potential risks.

The sugar glider (Petaurus breviceps) is a small, arboreal, nocturnal, gliding mammalian possum belonging to the marsupial infraclass. Exotic marsupials, including sugar gliders, are becoming popular companion pets and, consequently, the risk of potential infections that can be transmitted to humans should be investigated. Data on the role of the sugar glider as a possible carrier of pathogenic and zoonotic bacteria are scarce and fragmentary. Therefore, this study is aimed at evaluating the prevalence of potentially zoonotic bacteria (Salmonella spp., Escherichia coli, Campylobacter spp., Pseudomonas spp., Klebsiella spp., Listeria monocytogenes and Yersinia enterocolitica) in 64 sugar gliders kept as pets in Italy. The highest prevalence of infection pertained to members of the family Enterobacteriaceae, in particular Citrobacter spp. (50%), Enterobacter spp. (28·1%) and Klebsiella pneumoniae (15·6%); Pseudomonas aeruginosa was isolated from 10 out of 64 samples (15·6%). All strains of Klebsiella pneumoniae exhibited some level of resistance to multiple antimicrobials (ampicillin, amoxicillin-clavulanic acid and doxycycline). SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study show that sugar gliders may act as carriers of potentially pathogenic agents for humans and other animal species, therefore caution should be exercised in the handling and contact with these animals.

The optimal therapeutic strategy for locally advanced pancreatic cancer patients (LAPC) has not yet been established. Our aim is to evaluate how surgery after neoadjuvant treatment with either FOLFIRINOX (FFN) or Gemcitabine-NabPaclitaxel (GemNab) affects the clinical outcome in these patients. LAPC patients treated at our institution were retrospectively analysed to reach this goal. The group characteristics were similar: 35 patients were treated with the FOLFIRINOX regimen and 21 patients with Gemcitabine Nab-Paclitaxel. The number of patients undergoing surgery was 14 in the FFN group (40%) and six in the GemNab group (28.6%). The median Disease-Free Survival (DFS) was 77.10 weeks in the FFN group and 58.65 weeks in the Gem Nab group (p = 0.625), while the median PFS in the unresected group was 49.4 weeks in the FFN group and 30.9 in the GemNab group (p = 0.0029, 95% CI 0.138&ndash, 0.862, HR 0.345). The overall survival (OS) in the resected population needs a longer follow up to be completely assessed, while the median overall survival (mOS) in the FFN group was 72.10 weeks and 53.30 weeks for the GemNab group (p = 0.06) in the unresected population. Surgery is a valuable option for LAPC patients and it is able to induce a relevant survival advantage. FOLFIRINOX and Gem-NabPaclitaxel should be offered as first options to pancreatic cancer patients in the locally advanced setting.

Antimicrobial resistance is a public health concern worldwide and it is largely attributed to the horizontal exchange of transferable genetic elements such as plasmids carrying integrons. Several studies have been conducted on livestock showing a correlation between the systemic use of antibiotics and the onset of resistant bacterial strains. In contrast, although companion birds are historically considered as an important reservoir for human health threats, little information on the antimicrobial resistance in these species is available in the literature. Therefore, this study was aimed at evaluating the antimicrobial resistance of Escherichia coli and Pseudomonasaeruginosa isolated from 755 companion birds. Cloacal samples were processed for E. coli and P. aeruginosa isolation and then all isolates were submitted to antimicrobial susceptibility testing. P. aeruginosa was isolated in 59/755 (7.8%) samples, whereas E. coli was isolated in 231/755 (30.7%) samples. Most strains showed multidrug resistance. This study highlights that companion birds may act as substantial reservoirs carrying antimicrobial resistance genes which could transfer directly or indirectly to humans and animals, and from a One Health perspective this risk should not be underestimated.

Background: Recently, immune check-point inhibitors have shown efficacy in triple-negative breast cancer (TNBC). Since Hedgehog (Hh) signalling mediates crosstalk between breast cancer cells and tumor-infiltrating immune cells, we investigated the mechanisms by which Hh can modulate PDL1 expression and the tumor-immune microenvironment. Methods: TNBC tumors from untreated patients were subjects to PDL1 and Gli1 expression analysis by IHC. The correlation of Hh pathway activation and PDL1 expression was assessed in TNBC cells treated with the SMO-inhibitor NVP-LDE225. The main aim was to study the PDL1/Gli1 cross-talk. Results: The expression of PDL1 and Gli1, the major indicator for the canonical Hh signaling activation, were assessed by IHC in a tissue microarray (TMA) of TNBC samples from 237 untreated patients. In 203/237 cases we could analyze both PDL1 and Gli1 protein expression. A significant correlation between PDL1 and Gli1 expression was found. Indeed, of 77/203 (38%) PDL1 positive tumors 42/77 (54%) expressed Gli1. In order to explore correlations between other Hh pathway members and PDL1 in TNBCs, we interrogated the open-access database TCGA; PDL1 positive TNBCs showed high levels of SMO and PTCH1, Hh pathway receptors (Q-value 0.018 and 0.010). To better understand the link between Hh pathway and PDL1, we selected a panel of TNBC cell lines; the pharmacological Hh pathway inhibition led to a reduction of PDL1 protein and mRNA. On the other hand, engineered cells harbouring Gli1 overexpression showed higher levels of PDL1. Therefore, we hypothesized that Hh pathway could be involved in the PDL1 transcriptional modulation. To address this issue, we performed a luciferase reporter assay and a ChIP analysis following by PCR amplification of the PDL1 gene promoter. We found that Gli1 binds the PDL1 promoter, indicating that Gli1 transcriptionally enhances PDL1 expression. Gli1 expression was evaluated also in 4T1 cells, a TNBC murine model; furthermore, in 4T1 cells PDL1 protein expression was inhibited by NVP-LDE225. In vivo experiment will be performed in Balb/C mice orthotopically xenografted with 4T1 cells to confirm the role of Hh pathway to modulate the PDL1 expression and the tumor microenviroment in vivo. Conclusions: Our results suggest that Hh pathway has a crucial role in cancer immune evasion trough PDL-1 modulation. Due to their ability to target both tumor cells and the tumor microenvironment, Hh inhibitors could represent promising therapeutics to be clinically investigated in Gli1 overexpressing TNBC patients. Citation Format: Pietro De Placido, Concetta Di Mauro, Daniela Esposito, Ada Pesapane, Stefania Belli, Fabiana Napolitano, Antonio Santaniello, Priscilla Cascetta, Annachiara Carratù, Eleonora Mozzillo, Roberta Marciano, Alberto Servetto, Roberto Bianco, Luigi Formisano. Hedgehog pathway is involved in cancer immune surveillance through PDL1 modulation [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-04-17.

Background The aim of this study was to evaluate the efficacy of animal-assisted therapy (AAT) in elderly patients affected by Alzheimer's disease based on the formal reality orientation therapy (ROT) protocol. Methods Our study was carried out at an Alzheimer's centre for 6 months. A homogeneous sample (age, Mini-Mental State Examination (MMSE), 15-item Geriatric Depression Scale (GDS)) of 50 patients was selected at random and successively. Patients were divided into three groups: (i) 20 patients received a course of AAT (AAT group) based on the ROT protocol; (ii) 20 patients were engaged exclusively in activities based on the ROT group; and (iii) 10 patients (control group) participated in no stimulations. MMSE and GDS were administered at time 0 (T0) and time 1 (T1) to all three groups. Differences within groups between T0 and T1 for GDS and MMSE scores were analyzed by Student's t-test. Differences between group means were analyzed using an anova test with the Bonferroni-Dunn test for post-hoc comparisons. Results Both the AAT group and ROT group had improved GDS scores and showed a slight improvement in terms of mood. On the GDS, the AAT group improved from 11.5 (T0) to 9.5 (T1), and the ROT group improved from 11.6 (T0) to 10.5 (T1). At the same time, a slight improvement in cognitive function, as measured by the MMSE, was observed. In the AAT group, mean MMSE was 20.2 at T0 and 21.5 at T1, and in the ROT group, it was 19.9 at T0 and 20.0 at T1. In the control group, the average values of both the GDS and MMSE remained unchanged. The Bonferroni-Dunn results showed statistically significant differences between groups, particularly between the AAT group and the other two (P < 0.001). Conclusions Pet therapy interventions based on the formal ROT protocol were effective and, compared to the ROT, provided encouraging and statistically significant results.

Authors discuss some criteria they found useful for an Animal Assisted Education (AAE) intervention in a primary school aimed to promote, in children, interaction with animals, helping them to acknowledge their own emotions and those of others. Generally, these interventions are considered as a valid support for children with emotional or behavioral disorders, but they can also be an interest of Health Psychology as a protective factor against marked statuses of stress, anxiety and difficulties in training programs. In this paper, authors propose an intervention realized according Guidelines proposed in the Federico II Model for Pet Therapy, with a team was made by a psychologist and a veterinarian, with a specific training in Human–Animal Interaction (HAI), a dog and three donkeys. The intervention, addressed to 21 students belonging to a third grade class (8 years old), aimed to promote a contact with primary emotions such as joy, anger, fear, sadness, disgust, surprise. The proposed activities, guided by a playful approach, helped children to recognize and understand these emotions and to develop their relational skills.

A recent review on the prevalence of zoonotic bacteria in organic and conventional farms of cattle, pigs and poultry in the United States and Europe showed no differences between the presence of zoonotic agents and the type of the farm management [1, 2]. This study was undertaken both to evaluate the presence of zoonotic infectious agents not included in the National Control Planes for the animals presents in Farms open to public (FoP) and, consequently, to emphasize the importance of the role of the veterinary doctor with training in interspecies relationship in this context. From September 2014 to July 2016 thirty-two FoP of Campania Region have been chosen basing on the size farm population (at least 25 subjects from three different species) and then sampled. In each farm, in respect of animal welfare, rectal and cloacal swabs were collected in order to isolate Salmonella spp., Shigatoxins producing Escherichia coli (STEC) and thermotolerant Campylobacter by cultural and molecular methods. A total of 800 animal divided in dogs (34), cats (45), horses (82), donkeys (91), cattle (127), sheep (62), goats (73), pigs (41), leporidae (173), henhouse (32) and "other samples" such as eggs and other animal species (40) were sampled. In our study, all farms were positive to STEC and/or thermotolerant Campylobacter, conversely they were all time negative for Salmonella spp. In particular, a total of 124/800 (15.5%) strains of STEC were isolated primarily from poultry and donkeys followed by other animal species. Finally, 127/800 (15.87%) strains of thermotolerant Campylobacter were isolated primarily from poultry followed by other animal species [48/127 (37.79 %) C. jejuni (mainly from donkeys) and 79/127 (62.20%) C. coli (mainly from poultry)]. All positive animals to STEC and thermotolerant Campylobacter were clinically healthy. The healthcare monitoring carried out in FoP of Campania region, where the animals are raised primarily for zooanthropological purposes, has provided interesting data increasing the international scientific literature in the field of zoonoses. In this study some of the major gastrointestinal zoonoses linked to animals in the FoP were considered as well as the role of the veterinary doctor in the prevention and control of zoonotic diseases and in health education of the operator in the FoP. In fact, both the operators and visitors (families, school groups, children, elderly etc.) often underestimates the potential health risks caused by contact with FoP animals.

The incidence of campylobacteriosis have increased in both developed and developing countries over the last 10 years [1]. Several avian species are considered the main reservoirs of Campylobacter spp. [2,3]. Nevertheless, current scientific knowledge on the presence of Campylobacter spp. in pet birds is scarce. To address this lack of information, the present study was undertaken with the aim to evaluate the presence of these microorganisms in pet birds bred in southern Italy. To achieve this goal, 14 bird farms located in the Campania region (southern Italy) were visited. In each farm, bird farm population ranged between 20 to 100 animals belonging to the families of Estrildidae, Fringillidae and Psittacidae, from which 33, 28, and 27 pooled faecal samples were collected respectively. Specifically, eighty-eight cages housing a total of 225 captive birds were examined. The cage was used as an epidemiological unit, and each cage housed from 1 to 5 birds. Each sample was stored in Amies Charcoal Transport Medium at 4°C, transported to the laboratory, and analyzed within 2 h of collection by cultural and molecular methods. A total of 12/88 (13.6%) cages were positive for Campylobacter spp. which was identified as C. coli. In particular, 7/33 (21.2%) cages came from Estrildidae and 5/27 (18.5%) cages came from Psittacidae family. The twentyeight cages coming from Fringillidae family were consistently negative. our results demonstrate that C. coli may be found in the intestines of apparently healthy pet birds which could be considered as a further potential carrier of C. coli for humans and other companion animals. The adoption of good hygiene practices when handling pet birds should be, therefore, promoted.