Survey on carbapenem-resistant bacteria in pigs at slaughter and comparison with human clinical isolates in Italy

This study is focused on resistance to carbapenems and third-generation cephalosporins in Gram-negative microorganisms isolated from swine, whose transmission to humans via pork consumption cannot be excluded. In addition, the common carriage of carbapenem-resistant (CR) bacteria between humans and pigs was evaluated. Sampling involved 300 faecal samples collected from slaughtered pigs and 300 urine samples collected from 187 hospitalised patients in Parma Province (Italy). In swine, MIC testing confirmed resistance to meropenem for isolates of Pseudomonas aeruginosa and Pseudomonas oryzihabitans and resistance to cefotaxime and ceftazidime for Escherichia coli, Ewingella americana, Enterobacter agglomerans, and Citrobacter freundii. For Acinetobacter lwoffii, Aeromonas hydrofila, Burkolderia cepacia, Corynebacterium indologenes, Flavobacterium odoratum, and Stenotrophomonas maltophilia, no EUCAST MIC breakpoints were available. However, ESBL genes (blaCTXM-1, blaCTX-M-2, blaTEM-1, and blaSHV) and AmpC genes (blaCIT, blaACC, and blaEBC) were found in 38 and 16 isolates, respectively. P. aeruginosa was the only CR species shared by pigs (4/300 pigs; 1.3%) and patients (2/187; 1.1%). P. aeruginosa ST938 carrying blaPAO and blaOXA396 was detected in one pig as well as an 83-year-old patient. Although no direct epidemiological link was demonstrable, SNP calling and cgMLST showed a genetic relationship of the isolates (86 SNPs and 661 allele difference), thus suggesting possible circulation of CR bacteria between swine and humans

Hydrocortisone has a protective effect on CyclosporinA-induced cardiotoxicity.

CyclosporinA (CsA) is an immunosuppressive drug which induces severe adverse effects such as cardiotoxicity and nephrotoxicity. In several therapeutic protocols CsA is used in association with corticosteroids to obtain better therapeutic results. Recently, our studies showed that CsA increases blood pressure while inhibit Nitric Oxide (NO) production in vivo. In this study we evaluated in rat cardiomyocytes the effects of CsA, used alone or in association with Hydrocortisone (HY), on intracellular calcium concentration, NO production and lipid peroxidation (MDA level). Our results demonstrated that CsA increased intracellular calcium and such effect was dose-dependent. HY used alone, slightly decreased intracellular calcium, while dramatically reduced CsA-induced calcium fluxes. CsA (3.2 muM) increased lipid peroxidation and this effect was blunted by HY. Both CsA and HY inhibited NO production in rat cardiomyocytes acting on this pathway synergically. Our results demonstrated that in rat cardiomyocytes, CsA toxicity is due to a calcium overload, which in turn induce lipid peroxidation and determines oxidative stress-induced cell injury. Treatment with HY effectively inhibits CsA-induced toxicity, decreasing lipid peroxiclation as well as calcium intracellular concentration. Our findings seem to suggest that glucocorticoids may be effective in reducing CsA-induced cardiotoxicity at concentrations which are consistent with current therapeutic doses

Predictors of early and late hepatocellular carcinoma recurrence

: Hepatocellular carcinoma (HCC) is the most frequent liver neoplasm, and its incidence rates are constantly increasing. Despite the availability of potentially curative treatments (liver transplantation, surgical resection, thermal ablation), long-term outcomes are affected by a high recurrence rate (up to 70% of cases 5 years after treatment). HCC recurrence within 2 years of treatment is defined as "early" and is generally caused by the occult intrahepatic spread of the primary neoplasm and related to the tumor burden. A recurrence that occurs after 2 years of treatment is defined as "late" and is related to de novo HCC, independent of the primary neoplasm. Early HCC recurrence has a significantly poorer prognosis and outcome than late recurrence. Different pathogenesis corresponds to different predictors of the risk of early or late recurrence. An adequate knowledge of predictive factors and recurrence risk stratification guides the therapeutic strategy and post-treatment surveillance. Patients at high risk of HCC recurrence should be referred to treatments with the lowest recurrence rate and when standardized to combined or adjuvant therapy regimens. This review aimed to expose the recurrence predictors and examine the differences between predictors of early and late recurrence

Sodium-Glucose Co-Transporters Family: Current Evidence, Clinical Applications and Perspectives

Sodium-glucose co-transporters (SGLTs) family members are involved in several vital biological functions. Except for SGLT3, they are involved in the mechanisms of active transport of sodium and glucose and several micromolecules. The discovery of functions and mechanisms of SGLT1 inhibition and, in particular, of SGLT2 has radically changed the natural history of some pathologies. SGLT2 inhibitors have revolutionized the therapeutic approach not only of type 2 diabetes mellitus but also of heart failure and chronic kidney failure. Considering the role played by the other SGLTs and the functions still unknown to date, clinical implications of the inhibition of SGLT2 could represent the prelude for a wider modulation of these cotransporters. A better understanding of the role and function of SGLTs could represent a revolution in the therapeutic approach in the hepatological, metabolic, neurological and oncological fields. The purpose of this review is to illustrate the knowledge currently available on SGLTs, its clinical implications and future perspectives

Impact of chronic liver disease on SARS-CoV-2 infection outcomes: Roles of stage, etiology and vaccination

Since the first identification in December of 2019 and the fast spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, it has represented a dramatic global public health concern. Though affecting mainly the respiratory system, SARS-CoV-2 disease, defined as coronavirus disease 2019 (COVID-19), may have a systemic involvement leading to multiple organ dysfunction. Experimental evidence about the SARS-CoV-2 tropism for the liver and the increasing of hepatic cytolysis enzymes during infection support the presence of a pathophysiological relationship between liver and SARS-CoV-2. On the other side, patients with chronic liver disease have been demonstrated to have a poor prognosis with COVID-19. In particular, patients with liver cirrhosis appear extremely vulnerable to infection. Moreover, the etiology of liver disease and the vaccination status could affect the COVID-19 outcomes. This review analyzes the impact of the disease stage and the related causes on morbidity and mortality, clinical outcomes during SARS-CoV-2 infection, as well as the efficacy of vaccination in patients with chronic liver disease

HBV Infection and Host Interactions: The Role in Viral Persistence and Oncogenesis

Hepatitis B virus (HBV) is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Despite the advent of vaccines and potent antiviral agents able to suppress viral replication, recovery from chronic HBV infection is still an extremely difficult goal to achieve. Complex interactions between virus and host are responsible for HBV persistence and the risk of oncogenesis. Through multiple pathways, HBV is able to silence both innate and adaptive immunological responses and become out of control. Furthermore, the integration of the viral genome into that of the host and the production of covalently closed circular DNA (cccDNA) represent reservoirs of viral persistence and account for the difficult eradication of the infection. An adequate knowledge of the virus–host interaction mechanisms responsible for viral persistence and the risk of hepatocarcinogenesis is necessary for the development of functional cures for chronic HBV infection. The purpose of this review is, therefore, to analyze how interactions between HBV and host concur in the mechanisms of infection, persistence, and oncogenesis and what are the implications and the therapeutic perspectives that follow

Neoadjuvant and Adjuvant Systemic Therapies in Loco-Regional Treatments for Hepatocellular Carcinoma: Are We at the Dawn of a New Era?

: Despite maximizing techniques and patient selection, liver resection and ablation for HCC are still associated with high rates of recurrence. To date, HCC is the only cancer with no proven adjuvant or neoadjuvant therapy used in association to potentially curative treatment. Perioperative combination treatments are urgently needed to reduce recurrence rates and improve overall survival. Immunotherapy has demonstrated encouraging results in the setting of adjuvant and neoadjuvant treatments for non-hepatic malignancies. Conclusive data are not yet available in the context of liver neoplasms. However, growing evidence suggests that immunotherapy, and in particular immune checkpoint inhibitors, could represent the cornerstone of an epochal change in the treatment of HCC, improving recurrence rates and overall survival through combination treatments. Furthermore, the identification of predictive biomarkers of treatment response could drive the management of HCC into the era of a precision medicine. The purpose of this review is to analyze the state of the art in the setting of adjuvant and neoadjuvant therapies for HCC in association with loco-regional treatments in patients not eligible for liver transplantation and to hypothesize future scenarios

Mortality and risk factors of vaccinated and unvaccinated COVID-19 frail patients treated with anti-SARS-CoV-2 monoclonal antibodies. A real-world study

Background: There is a scarcity of data on outcomes and predictors of therapeutic failure of mAbs in frail COVID-19 patients. Methods: Prospective study including consecutive COVID-19 outpatients referred by primary care physicians for mAbs treatment. Outcomes evaluated were 60-day mortality, time to SARS-CoV-2 clearance, need for hospitalization, and O2-therapy. Results: Among 1026 COVID-19 patients enrolled, 60.2% received casirivamab/imdevimab and 39.8% sotrivimab. Median age was 63 years, 52.4% were males and median time from positive nasopharyngeal swab to mAbs administration was 3 days [IQR, 2-5]. 78.1% were vaccinated. Overall, 60-day mortality was 2.14%. No differences in outcomes were observed between the two mAbs used. No difference was observed in mortality between vaccinated and unvaccinated patients (p=0.925), although lower rate of hospitalization (p<0.005), less need for O2-therapy (p<0.0001) and reduced nasopharyngeal swab negativity time (p<0.0001) were observed in vaccinated. Early administration of mAbs was associated with lower mortality (p<0.007), while corticosteroid use worsened prognosis (p<0.004). Independent predictors associated with higher mortality were older age (p<0.0001), presence of active haematological malignancies (p<0.0001), renal failure (p<0.041) and need for O2-therapy (p<0.001). Conclusion: This study shows similar effectiveness among mAbs used regardless of vaccination status and identifies COVID-19 patients in whom mAbs have poor activity