Hepatic ischemia reperfusion injury (IRI) is not only a pathophysiological process involving the liver, but also a complex systemic process affecting multiple tissues and organs. Hepatic IRI can seriously impair liver function, even producing irreversible damage, which causes a cascade of multiple organ dysfunction. Many factors, including anaerobic metabolism, mitochondrial damage, oxidative stress and secretion of ROS, intracellular Ca(2+) overload, cytokines and chemokines produced by KCs and neutrophils, and NO, are involved in the regulation of hepatic IRI processes. Matrix Metalloproteinases (MMPs) can be an important mediator of early leukocyte recruitment and target in acute and chronic liver injury associated to ischemia. MMPs and neutrophil gelatinase-associated lipocalin (NGAL) could be used as markers of I-R injury severity stages. This review explores the relationship between factors and inflammatory pathways that characterize hepatic IRI, MMPs and current pharmacological approaches to this disease.

Since May 2022, a Monkeypox virus (MPXV) outbreak has been ongoing in several non‐endemic countries. MPXV is usually transmitted after intimate contact, through body fluids, close contact from active lesions or through respiratory droplets. The recent outbreak occurrent in people with multiple recent sexual intercourse suggests the sexual route as the main way of transmission. However, there is no sufficient evidence to consider MPXV as a new sexually transmitted infection (STI), even though we believe that a link between MPXV and other STIs may exist with a possible facilitating action on their spreading. Herein, we illustrate the first case described during the current outbreak of a young man with both MPXV and acute HIV infection in a non‐endemic country.

Background. Molnupiravir (MOL) and nirmatrelvir/ritonavir (NIR) were recently approved for the early treatment of COVID-19, but real-life data on tolerability, safety, and adverse events (AEs) are still scarce. Methods. We conducted a retrospective cohort study including all patients who were prescribed MOL and NIR at the Infectious Diseases Unit of Padua University Hospital, between January and May 2022. Demographic, clinical, and safety variables were recorded. Results. We included 909 patients, 48.3% males and 95.2% vaccinated against SARS-CoV-2. The median age was 73 (IQR: 62–82) years. MOL and NIR were prescribed in 407 (44.8%) and 502 (55.2%) patients, respectively. Overall, 124/909 (13.6%) patients experienced any AEs following antivirals intake: 98/124 (79%) patients reporting adverse events presented grade 1 AEs, 23/124 (18.5%) grade 2 AEs and 3 (2.5%) grade 3 AEs. Treatment discontinuation was recorded in 4.8% of patients. AEs were significantly higher in women, in patients treated with NIR compared to MOL and in people who were not vaccinated. Conclusions. In our real-life setting, AEs were higher than those reported by clinical trials, and were particularly associated with NIR use and with not being vaccinated. Further analyses are needed to better assess safety of oral antivirals and to define which patient’s profile may benefit most from MOL and NIR.

By increasing life expectancy of people living with HIV, the most clinical challenge is managing both drug-to-drug interactions and comorbidities (especially metabolic). Doravirine (DOR), a new non-nucleoside reverse transcriptase inhibitor, recently approved for the treatment of HIV, could be a good companion of dolutegravir (DTG) in a dual regimen for experienced elderly patients with multimorbidity and polypharmacy. We herein report our preliminary experience in a small cohort of elderly patients (>50 years of age) with multimorbidity and on polypharmacy who were switched to DOR/DTG dual regimen and followed-up for 3 months. The study was conducted at the Infectious and Tropical Diseases Unit of Padua University Hospital, Italy. Eighteen patients were included, 72.2% males and 27.8% postmenopausal women, mean age was of 61.3 years (7.6), 50% experienced AIDS events. Switches to DOR and DTG were mainly due to high cardiovascular and metabolic risk (72.2%), and interactions among comedications (50%). Antiretrovirals that subjects were switched off were mostly boosted protease inhibitors 66.7%. We observed a viral suppression among all subjects. Interestingly, we observed a statistically significant reduction in body mass index, body weight and waist circumference, eGFR, and a significant increase in serum creatinine levels. No significant changes in CD4+ T cell count was observed from the baseline. Lipid and fasting glucose values did not change significantly. To the best of our knowledge this is the first experience reporting real-life outcome of switch to DTG + DOR in elderly with multimorbidity and on polypharmacy. From our very preliminary data the dual combination of DTG and DOR could be a good treatment strategy for these subjects. However, our findings need to be validated on a greater number of patients.