La chetoacidosi diabetica nel cane e nel gatto

Diabetic ketoacidosis (DKA) is a serious complication of diabetes mellitus. Despite the expanding knowledge regarding the pathophysiology of DKA and the application of new treatment techniques for the complications, it remains a challenging disorder to treat. It is, in part, due to the deleterious impact that diabetic ketoacidosis has on multiple organ system and the frequent occurrence of concurrent often serious disorders that are responsible for the high mortality rate. Nevertheless, with logical therapy adapted to the individual and careful monitoring of clinical and clinicopathological parameters, the rate of therapeutic goal is high

Diabetic ketoacidosis in dogs and cats: new therapeutic approaches and monitoring tools

Complications induced by treatment of diabetic ketoacidosis (DKA) usually result from overly aggressive therapy, inadequate animal monitoring, and failure to reevaluate biochemical parameters in a timely manner. The thesis is divided into 6 studies focusing on new therapeutic and monitoring approaches during DKA treatment. Chapter 2 is an introduction to the topic and summarizes the current state of the art on DKA. Chapter 3 reports a study aimed at investigating the efficacy and safety of intravenous infusion of Lispro insulin in cats demonstrating that its use is associated with few side effects and the same effectiveness compared to regular insulin. Next up, two studies investigated the accuracy and precision of a glucometer (Gluco Calea, WellioVet) and a glucose-ketones meter (Belua, WellioVet) in dogs (Chapter 4) and cats (Chapter 5). Neither device is sufficiently accurate for use in dogs, while the superior performance of Belua glucometer support its clinical use in cats. In recent years, there has been great interest in devices measuring interstitial glucose. The aims of the study in Chapter 6 were to assess the performance of the FreeStyle Libre in dogs with DKA, and to determine the effect of body condition score (BCS), lactate concentration, severity of ketosis and acidosis on its accuracy. Although the ISO 15197:2013 criteria being only partially fulfilled, the clinical accuracy of the FreeStyle, unaffected by metabolic variables, supports its use. The effect of BCS requires further investigation. Finally, the thesis reports a study whose objective was to investigate which parameter between urinary acetoacetate (AcAc) and blood 3-beta-hydroxybutyrate (3-HB) was more suitable to define the end-point for insulin therapy during the treatment of DKA in dogs. The use of blood 3-HB does not reduce the time of insulin infusion and the time of hospitalization (Chapter 7).Le complicazioni secondarie al trattamento della chetoacidosi diabetica (DKA) sono generalmente conseguenti ad una terapia troppo aggressiva, ad un monitoraggio clinico inadeguato, oppure all’impossibilità di rivalutare sistematicamente alcuni parametri laboratoristici. La tesi si articola in 6 studi incentrati sulle nuove prospettive terapeutiche e di monitoraggio in corso di trattamento. Il Capitolo 2 costituisce un’introduzione all’argomento e riassume l’attuale stato dell’arte sulla DKA. Nel Capitolo 3 è riportato uno studio il cui scopo era indagare l’efficacia e la sicurezza dell’infusione endovenosa di insulina Lispro nella specie felina, dimostrando che il suo impiego è associato a minori effetti collaterali e alla stessa efficacia rispetto all’insulina regolare. A seguire, due studi hanno indagato l’accuratezza e la precisione di un glucometro (Gluco Calea, WellionVet) e di un glucometro/chetometro (Belua, WellionVet) nel cane (Capitolo 4) e nel gatto (Capitolo 5). Nessuno dei due dispositivi è risultato sufficientemente accurato da consentirne un utilizzo sicuro nel cane; diversamente, le superiori performance del glucometro Belua supportano l’impiego clinico nel gatto. Recentemente, è stato rivolto un grande interesse nei confronti dei dispositivi che misurano il glucosio interstiziale. Gli obiettivi dello studio riportato nel Capitolo 6 erano indagare le performance del FreeStyle Libre in cani con DKA e determinare l’effetto esercitato dal body condition score (BCS), dalla lattatemia, dalla gravità della chetosi e dell’acidosi sulla sua accuratezza. Sebbene i criteri ISO 15197:2913 siano stati solo parzialmente soddisfatti, l’accuratezza clinica del FreeStyle, non compromessa dalle variabili metaboliche, ne supporta l’impiego clinico. L’influenza esercitata dal BCS merita ulteriori indagini. Infine, è riportato uno studio il cui obiettivo era indagare quale parametro tra AcAc urinario e 3-HB ematico fosse più idoneo per definire l’endpoint della terapia insulinica in corso di trattamento della DKA nel cane. Lo studio dimostra che l’impiego del 3-HB non riduce la durata dell’infusione insulinica e dell’ospedalizzazione (Capitolo 7)

A Rare Case of Salmonella Spp. Osteomyelitis in a Dog

Osteomyelitis is an inflammatory condition of bone usually caused by infectious agents such as bacteria, fungi or viruses. The disease is characterized by systemic illness, pain and soft tissue swelling with visible radiographic alterations in bone. The most common bacteria isolated in cases of osteomyelitis in dogs and cats are Staphylococcus spp. (60% of cases), followed by Escherichia coli and Streptococcus spp. [1,2]. To our knowledge, this is the first canine case of Salmonella spp. osteomyelitis

Il tirocinio universitario secondo i tutor aziendali: un punto di vista centrale per un modello circolare e integrato

This paper aims to reflect on the intership model in first and second level degree courses in “Education and Training” at Sapienza University of Rome, exploring the viewpoint of tutors who follow students during theirtraining. The circular and integrated model allows to plan an appropriate training to achieve studying and working aims, considering students’ skills, knowledge and interests, taking into account also the labour market development.Data were collected through a semi-structured questionnaire administered at the end of the training experience and completed by 144 tutors. The results coming from the analysis are discussed underlining strengths and weaknesses of the internship program.L’intervento si propone di riflettere sul modello di tirocinio curricolare dei Corsi di Laurea in Scienze dell’educazione della Sapienza centrando l’attenzione sulle valutazioni dei tutor aziendali che seguono gli studenti nel corso del tirocinio. Il modello realizzato permette di pianificare un percorso formativo adeguato al raggiungimento degli obiettivi di studio e di lavoro, considerando competenze, conoscenze e interessi degli studenti, nonchè l’evoluzione del mercato del lavoro. Centrale è il monitoraggio dell’attività nelle sue fasi eper mezzo di differenti strumenti di rilevazione che consentono di cogliere i diversi punti di vista. Nel contributo, dopo una breve presentazione del modello, vengono approfondite le opinioni dei tutor aziendali. I dati sono stati raccolti attraverso un questionario semistrutturato, somministrato alla fine dell’esperienza di tirocinio e completato da 144 tutor. I risultati emersi dall’analisi permettono di sottolineare i punti di forza e di debolezza delmodello di tirocinio

Il tirocinio universitario secondo i tutor aziendali: un punto di vista centrale per un modello circolare e integrato

This paper aims to reflect on the intership model in first and second level degree courses in “Education and Training” at Sapienza University of Rome, exploring the viewpoint of tutors who follow students during theirtraining. The circular and integrated model allows to plan an appropriate training to achieve studying and working aims, considering students’ skills, knowledge and interests, taking into account also the labour market development.Data were collected through a semi-structured questionnaire administered at the end of the training experience and completed by 144 tutors. The results coming from the analysis are discussed underlining strengths and weaknesses of the internship program.L’intervento si propone di riflettere sul modello di tirocinio curricolare dei Corsi di Laurea in Scienze dell’educazione della Sapienza centrando l’attenzione sulle valutazioni dei tutor aziendali che seguono gli studenti nel corso del tirocinio. Il modello realizzato permette di pianificare un percorso formativo adeguato al raggiungimento degli obiettivi di studio e di lavoro, considerando competenze, conoscenze e interessi degli studenti, nonchè l’evoluzione del mercato del lavoro. Centrale è il monitoraggio dell’attività nelle sue fasi eper mezzo di differenti strumenti di rilevazione che consentono di cogliere i diversi punti di vista. Nel contributo, dopo una breve presentazione del modello, vengono approfondite le opinioni dei tutor aziendali. I dati sono stati raccolti attraverso un questionario semistrutturato, somministrato alla fine dell’esperienza di tirocinio e completato da 144 tutor. I risultati emersi dall’analisi permettono di sottolineare i punti di forza e di debolezza delmodello di tirocinio

Impact of Antigen Presentation Mechanisms on Immune Response in Autoimmune Hepatitis

The liver is a very tolerogenic organ. It is continually exposed to a multitude of antigens and is able to promote an effective immune response against pathogens and simultaneously immune tolerance against self-antigens. In spite of strong peripheral and central tolerogenic mechanisms, loss of tolerance can occur in autoimmune liver diseases, such as autoimmune hepatitis (AIH) through a combination of genetic predisposition, environmental factors, and an imbalance in immunological regulatory mechanisms. The liver hosts several types of conventional resident antigen presenting cells (APCs) such as dendritic cells, B cells and macrophages (Kupffer cells), and unconventional APCs including liver sinusoidal endothelial cells, hepatic stellate cells and hepatocytes. By standard (direct presentation and cross-presentation) and alternative mechanisms (cross-dressing and MHC class II-dressing), liver APCs presents self-antigen to naive T cells in the presence of costimulation leading to an altered immune response that results in liver injury and inflammation. Additionally, the transport of antigens and antigen:MHC complexes by trogocytosis and extracellular vesicles between different cells in the liver contributes to enhance antigen presentation and amplify autoimmune response. Here, we focus on the impact of antigen presentation on the immune response in the liver and on the functional role of the immune cells in the induction of liver inflammation. A better understanding of these key pathogenic aspects could facilitate the establishment of novel therapeutic strategies in AIH

Antibiotics or No Antibiotics, That Is the Question: An Update on Efficient and Effective Use of Antibiotics in Dental Practice

The antimicrobial resistance (AMR) phenomenon is an emerging global problem and is induced by overuse and misuse of antibiotics in medical practice. In total, 10% of antibiotic prescriptions are from dentists, usually to manage oro-dental pains and avoid postsurgical complications. Recent research and clinical evaluations highlight new therapeutical approaches with a reduction in dosages and number of antibiotic prescriptions and recommend focusing on an accurate diagnosis and improvement of oral health before dental treatments and in patients' daily lives. In this article, the most common clinical and operative situations in dental practice, such as endodontics, management of acute alveolar abscesses, extractive oral surgery, parodontology and implantology, are recognized and summarized, suggesting possible guidelines to reduce antibiotic prescription and consumption, maintaining high success rates and low complications rates. Additionally, the categories of patients requiring antibiotic administration for pre-existing conditions are recapitulated. To reduce AMR threat, it is important to establish protocols for treatment with antibiotics, to be used only in specific situations. Recent reviews demonstrate that, in dentistry, it is possible to minimize the use of antibiotics, thoroughly assessing patient's conditions and type of intervention, thus improving their efficacy and reducing the adverse effects and enhancing the modern concept of personalized medicine

The Evolving Role of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma Treatment

Hepatocellular carcinoma (HCC) is one of most common cancers and the fourth leading cause of death worldwide. Commonly, HCC development occurs in a liver that is severely compromised by chronic injury or inflammation. Liver transplantation, hepatic resection, radiofrequency ablation (RFA), transcatheter arterial chemoembolization (TACE), and targeted therapies based on tyrosine protein kinase inhibitors are the most common treatments. The latter group have been used as the primary choice for a decade. However, tumor microenvironment in HCC is strongly immunosuppressive; thus, new treatment approaches for HCC remain necessary. The great expression of immune checkpoint molecules, such as programmed death-1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), lymphocyte activating gene 3 protein (LAG-3), and mucin domain molecule 3 (TIM-3), on tumor and immune cells and the high levels of immunosuppressive cytokines induce T cell inhibition and represent one of the major mechanisms of HCC immune escape. Recently, immunotherapy based on the use of immune checkpoint inhibitors (ICIs), as single agents or in combination with kinase inhibitors, anti-angiogenic drugs, chemotherapeutic agents, and locoregional therapies, offers great promise in the treatment of HCC. This review summarizes the recent clinical studies, as well as ongoing and upcoming trials

Tumor necrosis factor‑α in systemic lupus erythematosus: Structure, function and therapeutic implications (Review)

: Tumor necrosis factor‑α (TNF‑α) is a pleiotropic pro‑inflammatory cytokine that contributes to the pathophysiology of several autoimmune diseases, such as multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis, psoriatic arthritis and systemic lupus erythematosus (SLE). The specific role of TNF‑α in autoimmunity is not yet fully understood however, partially, in a complex disease such as SLE. Through the engagement of the TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2), both the two variants, soluble and transmembrane TNF‑α, can exert multiple biological effects according to different settings. They can either function as immune regulators, impacting B‑, T‑ and dendritic cell activity, modulating the autoimmune response, or as pro‑inflammatory mediators, regulating the induction and maintenance of inflammatory processes in SLE. The present study reviews the dual role of TNF‑α, focusing on the different effects that TNF‑α may have on the pathogenesis of SLE. In addition, the efficacy and safety of anti‑TNF‑α therapies in preclinical and clinical trials SLE are discussed

Actors on the Scene: Immune Cells in the Myeloma Niche

Two mechanisms are involved in the immune escape of cancer cells: the immunoediting of tumor cells and the suppression of the immune system. Both processes have been revealed in multiple myeloma (MM). Complex interactions between tumor plasma cells and the bone marrow (BM) microenvironment contribute to generate an immunosuppressive milieu characterized by high concentration of immunosuppressive factors, loss of effective antigen presentation, effector cell dysfunction, and expansion of immunosuppressive cell populations, such as myeloid-derived suppressor cells, regulatory T cells and T cells expressing checkpoint molecules such as programmed cell death 1. Considering the great immunosuppressive impact of BM myeloma microenvironment, many strategies to overcome it and restore myeloma immunosurveillance have been elaborated. The most successful ones are combined approaches such as checkpoint inhibitors in combination with immunomodulatory drugs, anti-monoclonal antibodies, and proteasome inhibitors as well as chimeric antigen receptor (CAR) T cell therapy. How best to combine anti-MM therapies and what is the optimal timing to treat the patient are important questions to be addressed in future trials. Moreover, intratumor MM heterogeneity suggests the crucial importance of tailored therapies to identify patients who might benefit the most from immunotherapy, reaching deeper and more durable responses