Adipocyte differentiation of 3T3-L1 cells under tenofovir alafenamide, tenofovir disoproxil fumarate, and integrase strand transfer inhibitors selective challenge: an in-vitro model.

OBJECTIVE: Integrase strand transfer inhibitors (INSTIs) are a class of antiretroviral therapy (ART) medications with a good tolerability profile and a high genetic barrier to HIV drug resistance. However, several studies report significant weight gain among persons receiving INSTI-based ART regimens compared with other regimens. DESIGN: In-vitro model of adipogenesis. METHODS: We used 3T3-L1 cells to investigate the effects of the nucleoside reverse transcriptase inhibitors (NRTIs) tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF), alone or in combination with INSTIs: raltegravir (RAL), elvitegravir (ELV), dolutegravir (DTG), and bictegravir (BIC) on adipose differentiation. To monitor adipocyte differentiation, expression levels of PPARÉ£ and C/EBPα and the intracellular lipid accumulation by Red Oil staining were used. Furthermore, we evaluated the immunohistochemical expression of ER-TR7, a fibroblastic marker, after INSTIs treatment. RESULTS: Compared with control, INSTIs were able to increase adipogenesis, especially RAL and ELV. TAF and TDF inhibited adipogenesis alone and in combination with INSTIs. This ability was more evident when TAF was used in combination with DTG and BIC. Finally, INSTIs increased the expression of ER-TR7 compared with control and cells treated with TAF or TDF. CONCLUSION: Our data support the evidence that in-vitro challenge of 3T3-L1 cells with INSTIs is able to increase adipocytic differentiation and to drive a number of these cells toward the expression of fibroblastic features, with a different degree according to the various drugs used whereas TAF and TDF have an antagonistic role on this phenomenon.

Emergency department care of ABSSSI with dalbavancin infusion, direct discharge, and outpatient telemedicine follow up: a study protocol.

Novel therapeutic strategies such as the long-acting lipoglycopeptide antibiotics allow for the treatment and discharge of selected emergency department (ED) patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSI), who require intravenous antibiotics and would otherwise be hospitalized. The COVID-19 pandemic highlighted the need to develop strategies that may reduce hospitalization. The telehealth approach has shown success in remote management of cellulitis patients and could aid in the remote follow up of overall ABSSSI patients. This article describes a study protocol for the telemedicine follow up of patients diagnosed with ABSSSI in the ED, requiring intravenous treatment, receiving a single dalbavancin dose, and directly discharged. A telehealth system for remote follow up is evaluated as well as the possible inclusion of point-of-care ultrasound for the appropriate diagnosis of ABSSSI. The study will be conducted in compliance with regulatory requirements; and all collected data will be kept strictly confidential and in accordance with all relevant legislation on the control and protection of personal information. Dissemination of the study protocol may help increasing knowledge and awareness on this topic, with the aim of optimizing patient management, reducing hospitalization and lower the impact on healthcare associated costs.

Evolving epidemiology of HIV/AIDS in Campania region, 2011-2018: Is HIV/AIDS population in Campania different?

Objectives: Data on HIV/AIDS cases in Italy are collected using a standardised form. Regional epidemiology may vary. We described the epidemiological and clinical characteristics of newly diagnosed persons with HIV in the 'Cotugno' hospital in Naples during 2011-2018 and compared them with national data to identify similarities and differences. Methods: Data source for the Campania region is the data collection forms sent to the national surveillance system. The data source for the national data is from the periodic annual bulletins on HIV/AIDS published by the National Institute of Health. Results: In all, 1149 persons with HIV were diagnosed in 'Cotugno' (69.7% of those diagnosed in Campania). Persons with HIV in Campania showed many similarities with the Italian population: men were in the majority in both groups (about 75%), foreign origin was about 30%, heterosexuals were the most represented risk group, followed by men who have sex with men and injecting drug use in both samples. Some notable differences are also present. Among the risk factors for HIV acquisition, injecting drug use is significantly more common in Campania. Among the reasons for testing, significant differences are evident for almost all reasons, with screening activities (testing for concurrent diseases, for diagnosis of sexually transmitted diseases, screening in hospital during maternity care and screening in drug-addition services or prisons) being more common at the national level. The Campania population has a more severe disease pattern, with a significantly higher proportion of patients diagnosed with less than 200 CD4 cells/µL and AIDS. For each variable, we compared trends in the Campania region and in Italy using Spearman's correlation coefficient. Almost all trends show a weak correlation. Conclusion: In conclusion, the prevalence of injecting drug use is still consistent, and requires specific campaigns. The reasons for testing are different: screening activities work less in Campania than in Italy. This untimely approach contributes to a more severe clinical picture in Campania.

SARS-CoV-2 and inflammatory responses: From mechanisms to the potential therapeutic use of intravenous immunoglobulin.

A novel coronavirus (SARS-CoV-2) is responsible for a severe acute respiratory syndrome called coronavirus disease 2019 (COVID-19). It is originated in Wuhan, China, in December 2019. Due to its extreme transmissibility with droplets and human contacts, in a few months, it has become a pandemic. Nowadays, no effective therapy is available, and the scientific community is moving to find a therapeutic choice to fight this silent enemy. Studies are ongoing on several therapeutic options, including antiviral agents, immunomodulant drugs, and immunotherapy. Due to viral features, including the ability to start an inflammatory response that seems to be the fulcrum of COVID-19 pathogenic action, immunotherapy could represent a promising alternative waiting for the vaccine. High-dose intravenous immunoglobulin (IVIg), already used in other infectious diseases, could represent an effective help. The aim of this narrative review is to reassemble the clinical experiences on the use of IVIg in COVID-19 and the rationale of its use.

Hepatitis A virus strains circulating during 1997-2015 in Campania, a Southern Italy region with periodic outbreaks.

In Italy, the incidence of hepatitis A has progressively declined over the last 30 years, though not homogeneously throughout the country. In Campania, Southern Italy, high annual incidence rates have been reported and several periodic outbreaks have occurred. To investigate the phylogenetic and epidemiologic relationships among HAV strains circulating in Campania over the period 1997-2015, 87 hepatitis A cases were investigated. The most frequent risk factor was the consumption of raw/undercooked shellfish (75/87, 86.2%). During 1997-2002 most viral strains were subtype IA (16/23, 70%); the phylogenetic pattern suggests that the incidence peaks observed in 2000-2001 had likely been caused by multiple strains. During a large 2004 outbreak, almost all viral variants were subtype IB (38/41, 93%); most of them (22/38, 58%) were recognized to be one of two main strains (differing for just a single nucleotide), the remaining sequences were strictly related variants. In 2014/2015, only IA strains were observed; two phylogenetically related but distinct strains were responsible, respectively, for a small cluster in 2014 and an outbreak in 2015. In each outbreak, several strains unrelated to those responsible for most cases were detected in a minority of patients, documenting a background of sporadic cases occurring even in the course of outbreaks; some of them proved to be identical to strains detected 11-14 years previously. Overall, the data suggest that several related and unrelated HAV strains have endemically circulated over the last 15 years in Campania, with some strains gaining epidemic transmission likely because of a local combination of multiple factors, including inadequate waste water purification and dietary habits.

A family cluster of hepatitis A virus due to an uncommon IA strain circulating in Campania (southern Italy), not associated with raw shellfish or berries: a wake-up call to implement vaccination against hepatitis A?

Hepatitis A virus is a widely occurring disease, with different prevalence rates between countries in the North and West and those in the South and East. In Italy endemicity is low/medium, but not homogeneously distributed: in the northern/central regions a large hepatitis A outbreak due to genotype IA, related to the consumption of contaminated mixed frozen berries, occurred between 2013 and 2014, whereas in southern Italian regions recurrent outbreaks of hepatitis A, due to the IB genotype, still result from consumption of raw seafood. In 2014 an uncommon genotype IA strain was isolated from five patients (2 adults and 3 children) with hepatitis A, living in the surroundings of Naples (Campania) who did not have any of the most common risk factors for hepatitis A in Italy, such as consumption of raw shellfish or frozen berries, or travel to endemic countries. Moreover, based on the analysis of viral sequences obtained, this strain differed from several others in the national database, which had been recently isolated during Italian outbreaks. This case report reinforces the need to implement both information campaigns about the prevention of hepatitis A and vaccination programmes in childhood; in addition, it would be suitable to sequence strains routinely not only during large outbreaks of hepatitis A in order to obtain a more detailed national database of HAV strains circulating in Italy.

Vertical hepatitis C virus transmission: Main questions and answers.

Hepatitis C virus (HCV) affects about 3% of the world's population and peaks in subjects aged over 40 years. Its prevalence in pregnant women is low (1%-2%) in most western countries but drastically increases in women in developing countries or with high risk behaviors for blood-transmitted infections. Here we review clinical, prognostic and therapeutic aspects of HCV infection in pregnant women and their offspring infected through vertical transmission. Pregnancy-related immune weakness does not seem to affect the course of acute hepatitis C but can affect the progression of chronic hepatitis C. In fact, postpartum immune restoration can exacerbate hepatic inflammation, thereby worsening the liver disease, particularly in patients with liver cirrhosis. HCV infection increases the risk of gestational diabetes in patients with excessive weight gain, premature rupture of membrane and caesarean delivery. Only 3%-5% of infants born to HCV-positive mothers have been infected by intrauterine or perinatal transmission. Maternal viral load, human immunodeficiency virus coinfection, prolonged rupture of membranes, fetal exposure to maternal infected blood consequent to vaginal or perineal lacerations and invasive monitoring of fetus increase the risk of viral transmission. Cesarean delivery and breastfeeding increases the transmission risk in HCV/human immunodeficiency virus coinfected women. The consensus is not to offer antiviral therapy to HCV-infected pregnant women because it is based on ribavirin (pregnancy category X) because of its embryocidal and teratogenic effects in animal species. In vertically infected children, chronic C hepatitis is often associated with minimal or mild liver disease and progression to liver cirrhosis and hepatocarcinoma is lower than in adults. Infected children may be treated after the second year of life, given the adverse effects of current antiviral agents.