Natural History and Management of Hepatitis C in Children: 25 Years Experience of a Reference Center in Northern Italy.

Hepatitis C virus (HCV) infection natural history and management in the pediatric population are still debated. We retrospectively evaluated the outcome of a HCV pediatric population managed at the Pediatric Infectious Disease Unit of Luigi Sacco Hospital (Milan, Italy) from January 1997 to January 2022 (median follow-up 10 years) and we focused on the role of new drugs and transient elastography. Fifty-seven patients were enrolled: 8 (14%) had a spontaneous clearance, 33 were treated (58%), 7 (12%) were not treated because they were under 12 years old and 9 were lost at follow-up. HCV RNA was undetectable in all treated patients at the end of therapy, after 12 weeks (SVR12) and for the rest of their follow-up. All patients treated underwent elastography before and 1 year after therapy. Median stiffness pretherapy was 5.6 kPa, and 9 patients (16%) had abnormal transient elastography (>7 kPa, median 8.7 kPa). Median stiffness after treatment in the abnormal group was 6.8 kPa. Direct-acting antiviral agents are a safe and effective therapy for HCV chronic infection in the pediatric population. Liver elastography is normal in many vertically infected children before 12 years, but, when abnormal, it shows a significant improvement after direct-acting antiviral agent treatment. Further studies are needed to evaluate the role of elastography at diagnosis and follow-up in children.

Dietary intervention for children and adolescents with familial hypercholesterolaemia.

Familial hypercholesterolaemia (FH) is a frequent genetic disorder characterised by high plasma levels of total and LDL-cholesterol and premature atherosclerosis. If left untreated, affected subjects have a high risk of cardiovascular disease, as they are exposed to very high levels of LDL-cholesterol from birth. Healthy dietary habits and lifestyle are the first treatment option and, if started from childhood, represent a milestone in the prevention of atherosclerotic disease, both as a starting point and in combination with drug therapy. In this work, based on the main consensus documents available so far, we have evaluated the most up-to-date indications of the dietetic-nutritional intervention for the treatment of FH, delving into the peculiar aspects of the diet of the child/adolescent affected by FH. After an analysis of the macro- and micronutrients and the most common dietary patterns currently recommended, we highlighted some practical aspects, some frequent errors and some risks we could fall into when dealing with paediatric nutritional treatment. In conclusion, the dietary intervention for the child/adolescent with FH is a complex task, that should be individualised and tailored taking into account, first of all, the nutritional adequacy for growth and development, but also the multiple aspects linked to the child/adolescent's age, tastes and preferences, the family they belong to, the socio-economic context and the Country they live in.

Humoral and cell-mediated immune responses in HIV-vertically infected young patients after three doses of the BNT162b2 mRNA SARS-CoV-2 vaccine.

Background: Data on the efficacy of three SARS-CoV-2 mRNA BNT162b2 vaccine doses and the role of previous SARS-CoV-2-infection in enhancing vaccine immunogenicity in HIV-vertically-infected people living with HIV (PLWH) are limited, as is the duration of vaccine-induced responses. Methods: SARS-CoV-2 plasma neutralizing activity (NA) against the European (B.1), Delta (B.1.617.2) and Omicron (B.1.1.529) variants and cell-mediated immunity (CMI) were analyzed in 29 ART-treated young PLWH (mean age 27.9 years) and 30 healthy controls (HC) who received three BNT162b2 vaccine doses. Individuals were stratified based on the presence/absence of previous SARS-CoV-2 infection (infected and vaccinated -SIV-; uninfected and vaccinated -SV-). Analyses were performed before vaccination (T0), 25 days from the second dose (T1), the day the third dose was administered (T2), and 3 months after the third dose (T3). Results: In PLWH: i) NA against all variants was higher in SIV compared to SV at T2 and was increased at T3; ii) switched-memory plasmablasts were augmented in SIV alone at T2 and T3; iii) a SARS-CoV-2 specific T cell memory was generated; iv) IFN-γ-secreting CD4+ and CD8+ T lymphocytes were boosted at T3 mainly in SV. CMI magnitude was reduced in PLWH compared to HC. Notably, after the third dose of vaccine viremia was unmodified, but CD4 T cell counts were reduced>20% in 3/29 PHLW. Conclusion: A third dose of BNT162b2 vaccine induces strong humoral and CMI responses in young ART-treated PLWH independently from a previous SARS-CoV-2 natural infection. The lower magnitude of CMI responses should be considered when planning mRNA vaccine booster doses in PLWH.

Sex and age dimorphism of the gut-brain axis in ischemic stroke: A systematic review of preliminary studies.

Recent studies have shown that stroke risk and outcomes are influenced by the microbiota composition and its strict relationship with the immune system. Age and sex are the main non-modifiable factors that shape microbiome composition. In order to evaluate the effects of these two variables on the microbiome in stroke pathogenesis we performed a systematic review of literature, including 10 studies in the final selection. In the critical analysis of data we focused on three aspects: gut permeability, molecular mediators (both inflammatory molecules and gut metabolites) and functional deficits. Males display higher post-stroke intestinal permeability than females and a youthful microbiome correlates with higher levels of mucin gene expression thus enhancing intestinal barrier function. Gut mast cells-derived histamine shows an age-dependent increase after stroke but it remains unknown whether it also shows sexual dimorphism in the context of stroke. IL-17 is significantly increased in males as compared to females. SCFAs promote recovery in aged mice. We registered a lack of evidence on the impact of hormonal differences on the stroke microbiome. An overall negative effect of aged microbiota on functional tests after stroke is a robust finding among many studies. However, the effects of sex-mediated microbiome variability on functional deficits after stroke remain elusive. The modifiable nature of the microbiome makes it suitable for therapeutic intervention, however we show that a lack of consideration for sex as a biological variable is a major limitation of current stroke clinical and pre-clinical microbiome research studies.

The impact of preoperative anxiety on patients undergoing brain surgery: a systematic review.

Preoperative anxiety is a common reaction exhibited by up to 80% of patients who are scheduled for surgical procedures and characterized by psychological and physical changes which may affect their perioperative period. Our aim is to report the most up-to-date evidence on preoperative anxiety in brain surgery patients through a systematic analysis of the studies produced in the last decades. We performed a systematic review of literature by searching PubMed, Embase, and Cochrane Library databases. Data were extracted using the Population, Intervention, Comparison, Outcome framework and critically analyzed. PRISMA guidelines were applied, and the risk of bias of the included studies was assessed using the Risk of bias (RoB) 2 and ROBINS tools, as was the methodological quality, following GRADE criteria. We included 27 articles, accounting for 2558 patients in twelve different countries. The prevalence of preoperative anxiety ranged from 17 up to 89%, higher in female patients. Preoperative anxiety was associated with lower quality of life and cognitive performance, higher need for information, poorer memory and attention, longer hospitalization, depressive symptoms, and increase of physical disability; no correlation with survival rate was found. Seven randomized controlled trials attested the efficacy of acupuncture, music therapy, virtual reality, and pharmacological support in lowering anxiety levels. Preoperative anxiety is a common phenomenon that could negatively affect the perioperative period of brain surgery patients: this is something that should not be neglected to achieve better care through early prevention and optimal management.