Host factors and early treatments to restrict paediatric HIV infection and early disease progression

open6noA body of evidence indicates that a threshold level of the virus is required to establish systemic and persistent HIV infection in the host and that this level depends on virus-host interactions. Mother-to-child transmission (MTCT) of HIV is the main source of paediatric HIV infection and occurs when the host's immune system is still developing. Thus, innate resistance and immunity, rather than adaptive immune response, may be the main drivers in restricting the establishment of HIV reservoirs and the long-lived persistence of HIV infection in infants. Genetic variations in HIV co-receptors and their ligands, as well as in Toll-like receptors and defensins, key elements of innate immunity, have been demonstrated to influence the risk of perinatal HIV infection and disease progression in HIV-infected infants. Early treatments with combined antiretroviral therapy (cART) restrict paediatric infection by reducing the level of the transmitted/infecting virus to below the threshold required for the onset of immune response to the virus and also significantly reduce HIV reservoirs. However, despite long periods with no signs and symptoms of HIV infection, all early cART-treated children who later discontinued cART had a rebound of HIV, except for one case in whom a period of viral remission occurred. Which parameters predict viral remission or viral rebound after cART discontinuation? Could early cART prevent rather than just reduce the establishment of viral reservoirs? And, if so, how? Answers to these questions are also important in order to optimise the use of early cART in infants at high risk of HIV infection.openGianesin, Ketty; Petrara, Raffaella; Freguja, Riccardo; Zanchetta, Marisa; Giaquinto, Carlo; DE ROSSI, AnitaGianesin, Ketty; Petrara, Raffaella; Freguja, Riccardo; Zanchetta, Marisa; Giaquinto, Carlo; DE ROSSI, Anit

Accelerated aging in perinatally HIV-infected children: clinical manifestations and pathogenetic mechanisms

BACKGROUND: Premature aging and related diseases have been documented in HIV-infected adults. Data are now emerging also regarding accelerated aging process in HIV-infected children. METHODS: A narrative review was performed searching studies on PubMed published in English language in 2004-2017, using appropriate key words, including "aging", "children", "HIV", "AIDS", "immunosenescence", "pathogenesis", "clinical conditions". RESULTS: Premature immunosenescence phenotype of B and T cells in HIV-infected children is mediated through immune system activation and chronic inflammation. Ongoing inflammation processes have been documented by increased levels of pathogen-associated molecular patterns (PAMPS), increased mitochondrial damage, higher levels of pro-inflammatory cytokines, and a positive correlation between sCD14 levels and percentages of activated CD8+ cells. Other reported features of premature aging include cellular replicative senescence, linked to an accelerated telomeres shortening. Finally, acceleration of age-associated methylation pattern and other epigenetic modifications have been described in HIV-infected children. All these features may favor the clinical manifestations related to premature aging. Lipid and bone metabolism, cancers, cardiovascular, renal, and neurological systems should be carefully monitored, particularly in children with detectable viremia and/or with CD4/CD8 ratio inversion. CONCLUSION: Aging processes in children with HIV infection impact their quality and length of life. Further studies regarding the mechanisms involved in premature aging are needed to search for potential targets of treatment

The role of the Paediatric Initiative

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Vaccine impact: Benefits for human health

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Feasibility analysis of an ultrasound on line diagnostic approach for oral and bone surgery

During implant surgery procedures, surgical precision is an essential prerequisite for the functional and aesthetic success of the prosthetic crown to be placed on the dental implant. A modern implant surgical approach should be standardized as much as possible to guarantee extreme precision in the insertion of the implant into the upper and lower bone jaws. Among the most common surgical errors during implant surgery there is the over-preparation of the surgical alveolus with possible damage to the contiguous anatomical structures. To avoid this problem, in the recent years, there has been an increasing attention to the development of new control techniques. In this paper, we describe an innovative ultrasound approach, which exploits the integration of an electro-acoustic transducer with the surgical drill used for realizing the alveolus in the bone that will host the implant. Specifically, he proposed approach is based on the "time-of-flight" detection technique for measuring the thickness of the residual bone subjected to the drilling. In order to demonstrate the feasibility of the proposed approach, here we report on a detailed numerical analysis aimed at studying the propagation of ultrasonic waves through the drill-bit and through the involved tissues. The obtained results confirm the validity of our approach, and enable for a future first prototype implementation of a hi-tech surgical drill-bit, which in general is suitable not only for dental implant surgery but also for other uses in oral surgery, maxillofacial surgery and for bone surgery

Paediatric medicine issues and gaps from healthcare workers point of view: survey results and a narrative review from the global accelerator for paediatric formulations project

The WHO Model List of Essential Medicines for Children (EMLc) has not been systematically revised in the last few years. We conducted a survey addressed to healthcare professionals prescribing, preparing, or administering medicines to children and a narrative review to identify problematic paediatric formulations or missing medicines in all therapeutic fields to inform the review of the EMLc in 2023. A total of 285 physicians (63%), 28 nurses (6%) and 142 pharmacists (31%), mostly working in the hospital setting, reported at least one problematic medicine. 290 medicines were reported as missing (completely or the child-appropriate formulation). The top three most mentioned were ciprofloxacin together with phenobarbital and omeprazole. 387 medicines were reported as problematic (34% were oral liquid formulations, 34% tablets, 18% parenteral preparations. Mostly of the products were antibacterials (27%), cardiovascular medicines (11%) and antivirals (11%). The obtained responses show the perspective of healthcare workers working around the world, particularly in the European region (25%), in the African region (24%), and in the Region of the Americas (19%), with limited representation from Northern Africa and the Middle East. Our results need to be analysed with the outputs of other ongoing works before specific products can enter the WHO-hosted Global Accelerator for Paediatric formulations network prioritisation process. Efforts to develop appropriate formulations for children should be accelerated so that the uncertainties associated with off-label drug preparation and use are minimised, and therapeutic benefits are optimised

Diet prescription in obese patients

Diet is a cornerstone in the treatment of obese patients with or without metabolic complications. To optimize outcome, diet treatment should always take into account factors such as the Body Mass Index, the timeframe for reaching the recommended weight loss, comorbidities (e.g. arterial hypertension, diabetes mellitus, renal disease, lipid abnormalities, hyperuricemia) and, finally, individual patient characteristics (e.g. habits, preferences, adherence capacity). Hypocaloric diets need to be adequately balanced in terms of glucides, lipids and proteins, vitamins and minerals. For these reasons the diet prescription for obese patients, particularly those with comorbidities or cardiovascular disease, should be under the guidance of expert nutrition professionals who are aware of the risks of an unbalanced diet

Vertical transmission of zika virus and its outcomes:a Bayesian synthesis of prospective studies

BACKGROUND: Prospective studies of Zika virus in pregnancy have reported rates of congenital Zika syndrome and other adverse outcomes by trimester. However, Zika virus can infect and damage the fetus early in utero, but clear before delivery. The true vertical transmission rate is therefore unknown. We aimed to provide the first estimates of underlying vertical transmission rates and adverse outcomes due to congenital infection with Zika virus by trimester of exposure.METHODS: This was a Bayesian latent class analysis of data from seven prospective studies of Zika virus in pregnancy. We estimated vertical transmission rates, rates of Zika-virus-related and non-Zika-virus-related adverse outcomes, and the diagnostic sensitivity of markers of congenital infection. We allowed for variation between studies in these parameters and used information from women in comparison groups with no PCR-confirmed infection, where available.FINDINGS: The estimated mean risk of vertical transmission was 47% (95% credible interval 26 to 76) following maternal infection in the first trimester, 28% (15 to 46) in the second, and 25% (13 to 47) in the third. 9% (4 to 17) of deliveries following infections in the first trimester had symptoms consistent with congenital Zika syndrome, 3% (1 to 7) in the second, and 1% (0 to 3) in the third. We estimated that in infections during the first, second, and third trimester, respectively, 13% (2 to 27), 3% (-5 to 14), and 0% (-7 to 11) of pregnancies had adverse outcomes attributable to Zika virus infection. Diagnostic sensitivity of markers of congenital infection was lowest in the first trimester (42% [18 to 72]), but increased to 85% (51 to 99) in trimester two, and 80% (42 to 99) in trimester three. There was substantial between-study variation in the risks of vertical transmission and congenital Zika syndrome.INTERPRETATION: This preliminary analysis recovers the causal effects of Zika virus from disparate study designs. Higher transmission in the first trimester is unusual with congenital infections but accords with laboratory evidence of decreasing susceptibility of placental cells to infection during pregnancy.FUNDING: European Union Horizon 2020 programme

Premature aging and immune senescence in HIV-infected children

Objective: Several pieces of evidence indicate that HIV-infected adults undergo premature aging. The effect of HIV and antiretroviral therapy (ART) exposure on the aging process of HIV-infected children may be more deleterious since their immune system coevolves from birth with HIV. Design: Seventy-one HIV-infected (HIV+), 65 HIV-exposed-uninfected (HEU), and 56 HIV-unexposed-uninfected (HUU) children, all aged 0\u20135 years, were studied for biological aging and immune senescence. Methods: Telomere length and T-cell receptor rearrangement excision circle levels were quantified in peripheral blood cells by real-time PCR. CD4+ and CD8+ cells were analysed for differentiation, senescence, and activation/exhaustion markers by flow cytometry. Results: Telomere lengths were significantly shorter in HIV+ than in HEU and HUU children (overall, P < 0.001 adjusted for age); HIV+ ART-naive (42%) children had shorter telomere length compared with children on ART (P = 0.003 adjusted for age). T-cell receptor rearrangement excision circle levels and CD8+ recent thymic emigrant cells (CD45RA+CD31+) were significantly lower in the HIV+ than in control groups (overall, P = 0.025 and P = 0.005, respectively). Percentages of senescent (CD28-CD57+), activated (CD38+HLA-DR+), and exhausted (PD1+) CD8+ cells were significantly higher in HIV+ than in HEU and HUU children (P = 0.004, P < 0.001, and P < 0.001, respectively). Within the CD4+ cell subset, the percentage of senescent cells did not differ between HIV+ and controls, but programmed cell death receptor-1 expression was upregulated in the former. Conclusions: HIV-infected children exhibit premature biological aging with accelerated immune senescence, which particularly affects the CD8+ cell subset. HIV infection per se seems to influence the aging process, rather than exposure to ART for prophylaxis or treatmen