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Abstract Discontinuation of antimicrobial stewardship programs (ASPs) and increased antibiotic use were described during SARS-CoV-2 pandemic. In order to measure COVID-19 impact on ASPs in a setting of high multidrug resistance organisms (MDRO) prevalence, a qualitative survey was designed. In July 2021, eighteen ID Units were asked to answer a questionnaire about their hospital characteristics, ASPs implementation status before the pandemic and impact of SARS-CoV-2 pandemic on ASPs after the 1st and 2nd pandemic waves in Italy. Nine ID centres (50%) reported a reduction of ASPs and in 7 cases (38.9%) these were suspended. After the early pandemic waves, the proportion of centres that restarted their ASPs was higher among the ID centres where antimicrobial stewardship was formally identified as a priority objective (9/11, 82%, vs 2/7, 28%). SARS-CoV-2 pandemic had a severe impact in ASPs in a region highly affected by COVID-19 and antimicrobial resistance but weaknesses related to the pre-existent ASPs might have played a role.

Abstract Introduction Transplantation among HIV positive patients may be a valuable therapeutic intervention. This study involves an HIV D+/R+ kidney–liver transplantation, where PBMC-associated HIV quasispecies were analyzed in donor and transplant recipients (TR) prior to transplantation and thereafter, together with standard viral monitoring. Methods The donor was a 54 year of age HIV infected woman: kidney and liver recipients were two HIV infected men, aged 49 and 61. HIV quasispecies in PBMC was analyzed by ultra-deep sequencing of V3 env region. During TR follow-up, plasma HIV-1 RNA, HIV-1 DNA in PBMC, analysis of proviral integration sites and drug-resistance genotyping were performed. Other virological and immunological monitoring included CMV and EBV DNA quantification in blood and CD4 T cell counts. Results Donor and TR were all ART-HIV suppressed at transplantation. Thereafter, TR maintained a nearly suppressed HIV-1 viremia, but HIV-1 RNA blips and the increase of proviral integration sites in PBMC attested some residual HIV replication. A transient peak in HIV-1 DNA occurred in the liver recipient. No major changes of drug-resistance genotype were detected after transplantation. CMV and EBV transient reactivations were observed only in the kidney recipient, but did not require specific treatment. CD4 counts remained stable. No intermixed quasispecies between donor and TR was observed at transplantation or thereafter. Despite signs of viral evolution in TR, HIV genetic heterogeneity did not increase over the course of the months of follow up. Conclusions No evidence of HIV superinfection was observed in the donor nor in the recipients. The immunosuppressive treatment administrated to TR did not result in clinical relevant viral reactivations.

We describe a challenging case of patient with metallo-beta-lactamase-producing Pseudomonas aeruginosa sternal osteomyelitis following aortic valve replacement with biological prosthesis. The strain exhibited a multidrug-resistance phenotype carrying the blaVIM-1 gene and belonged to the high-risk clone sequence type ST235. The patient was successfully treated with surgical debridement plus antibiotic therapy with ceftazidime/avibactam, aztreonam, and amikacin. Time-kill curves showed that this triple antibiotic combination at 1 × MIC was strongly synergic after 8 h, achieving 99.9% killing and maintaining this until 48 h.

Background. Cytomegalovirus (CMV) immunoglobulin (CMVIG) is used for the prophylaxis of CMV infection after transplantation. Beyond providing passive CMV-specific immunity, CMVIG exerts enhancing and suppressive immunomodulatory functions. Although the anti-inflammatory activities of CMVIG have been extensively documented, its immunostimulatory activities remain poorly characterized. Methods. This exploratory study analyzed the capacity of CMVIG to modulate cell-mediated innate and adaptive immunities in vitro on freshly isolated peripheral blood mononuclear cells (PBMCs) of CMV-seropositive and -seronegative healthy individuals, using interferon-γ (IFN-γ) enzyme-linked immunospot and intracellular cytokine staining assays. Results. We showed that CMVIG treatment increases the number of IFN-γ–secreting PBMCs of both CMV-seronegative and -seropositive individuals, indicating a global stimulatory effect on innate immune cells. Indeed, CMVIG significantly increased the frequency of natural killer cells producing the T helper cell 1–type cytokines tumor necrosis factor and IFN-γ. This was associated with the induction of interleukin-12–expressing monocytes and the activation of cluster of differentiation (CD) 4+ and CD8+ T cells, as measured by the expression of tumor necrosis factor and IFN-γ. Interestingly, stimulation of PBMCs from CMV-seropositive subjects with CMVIG-opsonized CMV antigens (phosphoprotein 65, CMV lysate) enhanced CD4+ and CD8+ T-cell activation, suggesting that CMVIG promotes the immunogenicity of CMV antigens. Conclusions. Our data demonstrate that CMVIG can stimulate effector cells of both innate and adaptive immunities and promote the immunogenicity of CMV antigens. These immunostimulatory properties might contribute to the protective effect against CMV infection mediated by CMVIG.

The paper examines the way jurists, since the glosses, until Jacques Cujas, analyzed the definition of feud within the interpretation of common law, in the light of the Oberto dell’Orto’s writings. By this perspective, this author reviews aspects of the feudary real situation as an useful domain, grounding the usufruct’s technical inadequacy to express it, as well as analyzing the fiefs’ later characterization as quasi-dominium, found mainly in legal thought of sixteenth and seventeenth centuries’ jurists

Only 4 months after the beginning of SARS-CoV-2 epidemic, the world is facing a global pandemic due to a complex and insidious virus that today constantly poses new challenges. In this study, we highlight a persistent shedding of SARS-CoV-2 RNA into the urine, even in patients with a negative nasopharyngeal swab and in patients considered recovered. What does it mean? Besides the fact that the kidney is a probable site of viral replication, the prolonged viral excretion is a matter of great concern for our drainage system contamination.

El texto realiza una aproximación a las Lecciones o Discursos pronunciados con motivo de la toma de posesión de las cátedras en Italia. Analiza las etapas más importantes desde la primera guerra mundial y llama la atención sobre las reflexiones de gran nivel que han constituido pasos adelante relevantes en el desarrollo de la dogmática jurídica de una rama disciplinar, como es, la iuscivilista. Estas Lecciones se caracterizaron por constituir una meditación doctrinal con un carácter proyectivo indudable dirigidas a la comunidad de los cultivadores de la dogmática jurídico privada.

Cytomegalovirus (CMV) infection is the most significant viral infection in hosts with compromised immune systems as solid organ transplant patients. Despite significant progress being made in the prevention of CMV disease in these patients, further therapeutic strategies for CMV disease and for the CMV reactivation prevention are needed. Here, we describe the outcome of the infusion of in vitro expanded CMV-reactive T-cells, taken from a healthy CMV-seropositive donor, in a liver-transplanted recipient with a refractory recurrent CMV. In this particular case, adoptive transfer of allogenic CMV-reactive T-lymphocytes resulted in the clearance of CMV infection and resolution of the pathological manifestations of the patient. In the study we also investigated circulating miRNAs, both cellular and viral, as potential biomarkers during the course of CMV infection. The results indicate that the infusion of allogenic CMV-reactive T-cells can be an effective strategy to treat CMV infection recurrence when the generation of autologous virus specific T cell clones is not possible.

Aloe has long been used as a traditional medicine for its numerous beneficial properties, which are mainly ascribed to β-polysaccharides and phenolic compounds including anthraquinones, anthrones and chromones. However, few studies on large animals are currently available. The effect of whole leaf Aloe arborescens homogenate on the in vitro rumen fermentative processes was tested using alfalfa hay and barley meal as substrates. The Aloe homogeneate was added at three different concentrations (0.4, 2.0 and 10.0 g L−1 of fermentation liquid). The same homogenate was dosed (200 g) orally and through the rumen cannula to three rumen cannulated heifers and orally to six lactating dairy cows to measure the rumen degradation of aloin and the transfer of aloin from the gut into the blood, respectively. The Aloe homogenate did not affect in vitro rumen fermentations and feed digestibility. The administration of Aloe homogenate did not negatively affect animal feed intake and health neither on the cannulated heifers nor on the dairy cows. Aloin underwent a rapid degradation in the rumen milieu, and became undetectable 2 h after oral dosage. However, when Aloe homogenate was administered to dairy cows, aloin appeared in blood as early as 2 h after administration, reached a maximum after 4 h (6.2 ± 5.8 μg L−1) and progressively decreased thereafter. These results suggest that Aloe compounds can be absorbed into the blood and encourage the study of Aloe as a potential nutraceutical in ruminants. Further studies should determine the most effective in vivo dosage.

Questioning the characteristics of modernity and post-modernity in law, this article examines the consequences that these characteristics may have had for the history of law. With the recognition of the social nature of the law, the consciousness of the historicity of law constitutes an essentiel conquest in the collective consciousness of the Europe of civil law.

The overall goal of this work was to develop a prototype expert system assisting quality control and traceability of particleboard panels on the production floor. Four different types of particleboards manufactured at the laboratory scale and in industrial plants were evaluated. The material differed in terms of panel type, composition, and adhesive system. NIR spectroscopy was employed as a pioneer tool for the development of a two-level expert system suitable for classification and traceability of investigated samples. A portable, commercially available NIR spectrometer was used for nondestructive measurements of particleboard panels. Twenty-five batches of particleboards, each containing at least three independent replicas, was used for the original system development and assessment of its performance. Four alternative chemometric methods (PLS-DA, kNN, SIMCA, and SVM) were used for spectroscopic data classification. The models were developed for panel recognition at two levels differing in terms of their generality. In the first stage, four among twenty-four tested combinations resulted in 100% correct classification. Discrimination precision with PLS-DA and SVMC was high (>99%), even without any spectra preprocessing. SNV preprocessed spectra and SVMC algorithm were used at the second stage for panel batch classification. Panels manufactured by two producers were 100% correctly classified, industrial panels produced by different manufacturing plants were classified with 98.9% success, and the experimental panels manufactured in the laboratory were classified with 63.7% success. Implementation of NIR spectroscopy for wood-based product traceability and quality control may have a great impact due to the high versatility of the production and wide range of particleboards utilization.

The author wishes to identify the legal message given by Europe in the Middle Ages and in contemporary times, when a legal entity was achieved therein. This message has ancient roots, but has the following common elements: achievement of a legal unit, while also respecting internal diversity; enhancement of the value of jurists in legal production (because law is the field of jurists, and not of politicians); and especially enhancement of the value of legal science, for its capacity to establish harmonising and generally boundless principles. It is singular that this enhancement of the value of jurists and legal science may also be found in the great movement often called legal globalisation, a movement borne of the needs of the global economic market, and in which jurists and legal science play a decisive part.

Venous thromboembolism (VTE) is defined as the obstruction, partial or complete, of one or more veins of deep circulation. It is a condition that can lead to a deterioration in his state of health until death, manifesting as deep vein thrombosis (DVT) or pulmonary embolism (PE). The major orthopedic surgery and the surgical oncology are frequently associated with thromboembolic complications, because of conditions that are often critical in these patients. It is estimated that in Italy DVT has an incidence that varies between 50 and 150 new cases per 100,000 population, while the prevalence would be between 2.5 and 5%. In the absence of thromboprophylaxis, the orthopedic surgery lead to a high increased risk of VTE. In elective hip replacement, in the absence of prophylaxis, the incidence of DVT and of fatal PE is about 50% and 2% respectively. In elective knee arthroplasty the risk of venous thromboembolic complications is even higher. It is estimated that 56.2% of the costs of prophylaxis with Low Molecular Weight Heparin (LMWH) in patients undergoing major orthopedic surgery are attributable to the cost of drugs (about € 200), followed (with 44.8%) by the cost of administration (approximately € 159). The average total cost/day was estimated at € 8 per patient. In Italy, it has been estimated an annual cost for new cases between 215 and 260 million €. The clinical advantages of the New Oral Anticoagulants (NOA) appear to be substantially clear, the major concern with regard to their reimbursement is therefore linked to the financial impact, due to the higher cost per day of the NOA compared with LMWH. To this end, it was built a model of budget impact, in the perspective of the Italian NHS, from the data related to cases of major surgical orthopedic procedures and a meta-analysis on the pivotal RCT, which aims to measure the differential effects in terms of prevention of VTE. The results show that the financial impact of the NOA in the prophylaxis of major orthopedic surgery is not particularly relevant. In fact, the major pharmaceutical costs that, at national level, amount to € 10.8 mil. (€ 15.2 mil. in the case of prolonged prophylaxis in knee operations) would be more than offset by savings in terms of fewer treatments of VTE, which is based on the assumption of more than 4,000 cases, up to about 6,600 in hypothesis best efficacy.

Duas preliminares elucidações, necessárias para a correta avaliação deste ensaio, o qual foi elaborado para uma conferência a ser ministrada ao plenário da Accademia dei Lincei, e, portanto, para um público de uma variadíssima formação, mas – o que se observa – somente em mínima parte formado por juristas. Impõem-se um linguajar jurídico de divulgação (que seria destoado no âmbito acadêmico), mas – este sim – voltado à comunicação e à compreensão. Os juristas presentes toleraram alguns esclarecimentos elementares que, para eles, são absolutamente pleonásticos e, sobretudo, a fuga por parte minha do excessivo tecnicismo do linguajar jurídico que frequentemente tem uma valência exotérica para os laicos. Escolhi, ainda, fazer um colóquio com os meus ouvintes tendo por base algumas notas; isso, com a finalidade de tornar menos enfadonha a conferência.

O presente artigo tem por objetivo exploraras descontinuidades entre os universos medievale moderno, enfocando, para tanto, as diferentesformas de a dimensão jurídica relacionar-secom a dimensão política e social, que, sobre basesantropológicas profundamente distintas (primeirocomunitária e, depois, individualista), identificama contraposição entre a “sociedade de sociedades”de origem medieval, e a insularidade doEstado, caracteristicamente moderna.This article has by purpose to explorethe discontinuities between the middle-aged andmodern universes, focusing, so for, the differentways to the juridical dimension to relate with thepolitical and social dimension, that, overanthropological bases deeply distint (firstcommunitarian and then individualist), identify thecounterposition between the “society of societies”from middle-aged source,and the State insularity,characteristicly modern.

O artigo realiza reflexão sobre opapel da história e do historiador do direitoquanto ao processo de formação do juristade nosso tempo e sobre o próprio desígnioinstitucional das Faculdades de Direito naatualidade. O historiador, estando ao ladodo operador do direito positivo, oferece contribuiçãoa uma saudável desmistificação dadogmática jurídica. Com isso, relegitimam-sereciprocamente o historiador e o jurista.This paper aims at reflecting aboutthe history and law historian’s roles accordingto his background learning process nowadays,as well as the institutional purpose of LawColleges nowadays. The historian, whenside by side to the positive law operator,contributes to a healthful juridical dogmaticnon-mystification. Thus, historian and juristlegitimate themselves again, respectively.

Introduction We designed a randomized, controlled prospective study aimed at comparing efficacy and tolerability of ezetimibe+fenofibrate treatment versus pravastatin monotherapy in dyslipidemic HIV‐positive (HIV+) patients treated with protease inhibitors (PIs). Methods We consecutively enrolled 42 HIV+ dyslipidemic patients on stable PIs therapy (LDL cholesterol >130 mg/dl or triglycerides 200–500 mg/dl with non‐HDL cholesterol >160 mg/dl). After basal evaluation, patients were randomized to a six‐month treatment with ezetimibe 10 mg/day+fenofibrate 200 mg/day or with pravastatin 40 mg/day. Both at the basal evaluation and after the six‐month treatment, the patients underwent blood tests for lipid parameters, and muscle and liver enzymes. Results At baseline, the two groups (21 patients each) were similar with regards to gender, age, BMI, blood pressure and virologic and metabolic parameters. After the six‐month therapy, total cholesterol, LDL cholesterol and non‐HDL cholesterol decreased significantly (p

The aim of this research was to study the consequences of ω3 fatty acids (FA) administration around calving on inflammatory response and on productive performances. In this period dairy cows undergo a metabolic challenge, coming with an inflammatory-like status triggering the release of pro-inflammatory mediators (e.g. eicosanoids, cytokines). Eicosanoids synthesis may be modulated by altering the ratio of their precursors (ω3 and ω6 FA). Ten cows received 22 g/d of rumen-protected ω3 FA from -21 to +21 days from calving (OPT), while 10 (CTR) received no supplement. Cows were frequently monitored for health status, body condition score (BCS), blood (metabolic, inflammatory and FA profiles), milk yield. OPT (vs CTR) showed a similar milk production, a numerically smaller BCS drop, lower postpartum levels of non-esterified fatty acids (P

Chapter 2 of L’ordine giuridico medievale, entitled « Premesse ordinative », presents the fundamental methodological issues at the heart of the book. After discussing the historicity of law, the author introduces the notions of « legal order » and « legal experience », which form the basis of his understading of medieval law. The Middle Ages are described as a unified experience, characterised by the presence of multiple legal orders.

With a point of departure in the relation from the civil law professor Pugliatti about property and properties, the article proposes to use the plural form in order to relativize the absolutist conception of property that has triumphed during the 19th century. The medieval experience is the one of another relationship between Man and Things, based on the possession and exploitation of land, and leading to the idea of a plurality of properties upon the same thing. Appeared during the early Middle Ages, this superposition of ownerships was theorized, thanks to the rediscovery of Justinian’s compilation, through the notions of dominium utile and divided domain. Although it was founded on a contradiction in the very terms of dominium utile, this juridical construction was anchored in mentalities during centuries. Finding its origin in the thought of theologians and of philosophers from the 14th century, the new anthropologic conception of the relationship of Man and Things gave birth to the possessive individualism and to the ‘modern’ property.

Paolo Grossi brings the perspective of a legal historian to the definition of political modernity. He deciphers the slow shift in the conception of law from the 14th century to the dawn of the 19th, focusing in particular on the kingdom of France. He seeks to demonstrate that political modernity is characterised by a process of individualisation that inverts the relationship between law and politics: whereas in the Middle Ages “first there is law; political power comes only later”, from now on “the basic certainty is that before law, there is the State”.

In this text – a written version of a lecture given at the Italian National School for the Judiciary in 2019 – Paolo Grossi begins by examining the legal nature of the Constitution and the relationship between the Republic and the State, highlighting the multi-layered nature of the Italian Constitution. Paolo Grossi invites to understand that living the constitutional dimension of the Republic today means respecting its inherent legal pluralism. For this reason, Paolo Grossi advocates moving « from law to interpretation », which is also possible thanks to the epistemological support of the « hermeneutic revolution ». Finally, from this perspective, he asks two fundamental questions : what about the « subordination of the judge to the law » ? What about the so-called separation of powers ?

This Paolo Grossi's text invites scholars of medieval legal history to get rid of two notions that the Italian jurist considers “cumbersome” and profoundly alien to the medieval legal experience, namely the notions of “sovereignty” and the “State”. To this end, Grossi contrasts a modern unitary model, in which the sovereign State is the only legitimate instance to legislate, with a medieval pluralist model characterized by a variety of sources, powers, and communities authorized to shape the law. Grossi highlights the analytical value of the notion of “autonomy” in understanding the plurality of medieval legal orders. In doing so, he highlights the idea of a “law without state”, that is fundamentally connected to the social world and expressing it in all its dimensions. The article offers a radical re-reading of medieval political and legal thought.