Pregnancy Loss in Women with HIV is not Associated with HIV Markers: Data from a National Study in Italy, 2001-2018.

BACKGROUND: There is limited information on pregnancy loss in women with HIV, and it is still debated whether HIV-related markers may play a role.Objectives: To explore potential risk factors for pregnancy loss in women with HIV, with particular reference to modifiable risk factors and markers of HIV disease. METHODS: Multicenter observational study of HIV-positive pregnant women. The main outcome measure was pregnancy loss, including both miscarriage (<22 weeks) and stillbirth ( 6522 weeks). Possible associations of pregnancy loss were evaluated in univariate and multivariate analyses. RESULTS: Among 2696 eligible pregnancies reported between 2001 and 2018, 226 (8.4%) ended in pregnancy loss (miscarriage 198, 7.3%; stillbirth 28, 1.0%). In multivariate analyses, only older age (adjusted odds ratio [AOR] per additional year of age: 1.079, 95% confidence interval [CI] 1.046-1.113), HIV diagnosis before pregnancy (AOR: 2.533, 95%CI 1.407-4.561) and history of pregnancy loss (AOR: 1.625, 95%CI 1.178-2.243) were significantly associated with pregnancy loss. No significant association with pregnancy loss was found for parity, coinfections, sexually transmitted diseases, hypertension, smoking, alcohol and substance use, CD4 cell count, HIV-RNA viral load, and CDC HIV stage. CONCLUSIONS: Older women and those with a previous history of pregnancy loss should be considered at higher risk of pregnancy loss. The severity of HIV disease and potentially modifiable risk factors did not increase the risk of pregnancy loss

Lipid profile during pregnancy in HIV-infected women

Purpose: We investigated the evolution of serum lipid levels in HIV-infected pregnant women and the potential effect of antiretroviral treatment during pregnancy using data from a national surveillance study. Method: Fasting lipid measurements collected during routine care in pregnancy were used, analyzing longitudinal changes and differences in lipid values at each trimester by protease inhibitors (Pls) and stavudine use. Multivariate analyses were used to control for simultaneous factors potentially leading to hyperlipidemia. Study population included 248 women. Results: Lipid values increased progressively and significantly during pregnancy: mean increases between the first and third trimesters were 141.6 mg/dL for triglycerides (p <.001), 60.8 mg/dL for total cholesterol (p <.001), 13.7 mg/dL for HDL cholesterol (p <.001), and 17.8 mg/dL for LDL cholesterol (p =.001). At all trimesters, women on PIs had significantly higher triglyceride values compared to women not on Pis. The effect of Pls on cholesterol levels was less consistent. Stavudine showed a dyslipidemic effect at first trimester only. Multivariate analyses confirmed these observations and suggested a potential role of other cofactors in the development of hyperlipidemia during pregnancy. Conclusion: The changes observed point to the need to further explore the causes and the clinical correlates of hyperlipidemia during pregnancy in women with HIV

High Levels of Receptor Tyrosine Kinases in CCM3-Deficient Cells Increase Their Susceptibility to Tyrosine Kinase Inhibition

Cerebral cavernous malformations (CCMs) are vascular malformations that can be the result of the deficiency of one of the CCM genes. Their only present treatment is surgical removal, which is not always possible, and an alternative pharmacological strategy to eliminate them is actively sought. We have studied the effect of the lack of one of the CCM genes, CCM3, in endothelial and non-endothelial cells. By comparing protein expression in control and CCM3-silenced cells, we found that the levels of the Epidermal Growth Factor Receptor (EGFR) are higher in CCM3-deficient cells, which adds to the known upregulation of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) in these cells. Whereas VEGFR2 is upregulated at the mRNA level, EGFR has a prolonged half-life. Inhibition of EGFR family members in CCM3-deficient cells does not revert the known cellular effects of lack of CCM genes, but it induces significantly more apoptosis in CCM3-deficient cells than in control cells. We propose that the susceptibility to tyrosine kinase inhibitors of CCM3-deficient cells can be harnessed to kill the abnormal cells of these lesions and thus treat CCMs pharmacologically

Improving diagnosis for rare diseases: the experience of the Italian undiagnosed Rare diseases network

Background For a number of persons with rare diseases (RDs) a definite diagnosis remains undiscovered with relevant physical, psychological and social consequences. Undiagnosed RDs (URDs) require other than specialised clinical centres, outstanding molecular investigations, common protocols and dedicated actions at national and international levels; thus, many "Undiagnosed RDs programs" have been gradually developed on the grounds of a well-structured multidisciplinary approach. Methods The Italian Undiagnosed Rare Diseases Network (IURDN) was established in 2016 to improve the level of diagnosis of persons with URD living in Italy. Six Italian Centres of Expertise represented the network. The National Centre for Rare Diseases at the Istituto Superiore di Sanita coordinates the whole project. The software PhenoTips was used to collect the information of the clinical cases. Results One hundred and ten cases were analysed between March 2016 and June 2019. The age of onset of the diseases ranged from prenatal age to 51 years. Conditions were predominantly sporadic; almost all patients had multiple organs involvements. A total of 13/71 family cases were characterized by WES; in some families more than one individual was affected, so leading to 20/71 individuals investigated. Disease causing variants were identified in two cases and were associated to previously undescribed phenotypes. In 5 cases, new candidate genes were identified, although confirmatory tests are pending. In three families, investigations were not completed due to the scarce compliance of members and molecular investigations were temporary suspended. Finally, three cases (one familial) remain still unsolved. Twelve undiagnosed clinical cases were then selected to be shared at International level through PhenomeCentral in accordance to the UDNI statement. Conclusions Our results showed a molecular diagnostic yield of 53,8%; this value is comparable to the diagnostic rates reported in other international studies. Cases collected were also pooled with those collected by UDNI International Network. This represents a unique example of global initiative aimed at sharing and validating knowledge and experience in this field. IURDN is a multidisciplinary and useful initiative linking National and International efforts aimed at making timely and appropriate diagnoses in RD patients who still do not have a confirmed diagnosis even after a long time

Italian good practice recommendations on management of persons with Long-COVID

A significant number of people, following acute SARS-CoV-2 infection, report persistent symptoms or new symptoms that are sustained over time, often affecting different body systems. This condition, commonly referred to as Long-COVID, requires a complex clinical management. In Italy new health facilities specifically dedicated to the diagnosis and care of Long-COVID were implemented. However, the activity of these clinical centers is highly heterogeneous, with wide variation in the type of services provided, specialistic expertise and, ultimately, in the clinical care provided. Recommendations for a uniform management of Long-COVID were therefore needed. Professionals from different disciplines (including general practitioners, specialists in respiratory diseases, infectious diseases, internal medicine, geriatrics, cardiology, neurology, pediatrics, and odontostomatology) were invited to participate, together with a patient representative, in a multidisciplinary Panel appointed to draft Good Practices on clinical management of Long-COVID. The Panel, after extensive literature review, issued recommendations on 3 thematic areas: access to Long-COVID services, clinical evaluation, and organization of the services. The Panel highlighted the importance of providing integrated multidisciplinary care in the management of patients after SARS-CoV-2 infection, and agreed that a multidisciplinary service, one-stop clinic approach could avoid multiple referrals and reduce the number of appointments. In areas where multidisciplinary services are not available, services may be provided through integrated and coordinated primary, community, rehabilitation and mental health services. Management should be adapted according to the patient's needs and should promptly address possible life-threatening complications. The present recommendations could provide guidance and support in standardizing the care provided to Long-COVID patients

Atazanavir and darunavir in pregnant women with HIV: Evaluation of laboratory and clinical outcomes from an observational national study

Background: Atazanavir and darunavir represent the main HIV PIs recommended in pregnancy, but comparativedata in pregnant women are limited.We assessed the safety and activity profile of these two drugs in pregnancyusing data from a national observational study.Methods: Women with atazanavir or darunavir exposure in pregnancy were evaluated for laboratory measuresand main pregnancy outcomes (e.g. preterm delivery, low birthweight, non-elective caesarean section and neonatalgestational age-adjusted birthweight Z-score).Results: Final analysis included 500 pregnancies with either atazanavir (n"409) or darunavir (n"91) exposure.No differences in pregnancy outcomes, weight gain in pregnancy, drug discontinuations, undetectable HIV-RNA,haemoglobin, ALT, total cholesterol, HDL cholesterol and LDL cholesterol were observed between the twogroups. At third trimester, exposure to darunavir was associated with higher levels of plasma triglycerides(median 235.5 versus 179 mg/dL; P"0.032) and a higher total cholesterol/HDL cholesterol ratio (median 4.03versus 3.27; P"0.028) and exposure to atazanavir was associated with higher levels of plasma bilirubin (1.54versus 0.32 mg/dL; P&lt;0.001).Conclusions: In this observational study, the two main HIV PIs currently recommended by perinatal guidelinesshowed similar safety and activity in pregnancy, with no evidence of differences between the two drugs in termsof main pregnancy outcomes. Based on the minor differences observed in laboratory measures, prescribingphysicians might prefer either drug in some particular situations where the different impacts of treatment onlipid profile and bilirubin may have clinical relevance

Good prenatal detection rate of major birth defects in HIV-infected pregnant women in Italy

What's already known about this topic? Exposure to antiretroviral treatment in pregnancy does not seem to increase the risk of birth defects, but there is no information on the rate of prenatal detection of such defects. What does this study adds? We provide for the first time, in a national case series, information about prenatal detection rate in women with HIV (51.6% for any major defect, 66.7% for chromosomal abnormalities, and 85% for severe structural defect

Pregnancy outcomes and cytomegalovirus DNAaemia in HIV infected pregnant women with CMV

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Community engagement and professionalization: Emerging tensions

© 2019 by Emerald Publishing Limited. An increase in community engagement by governments across Australia’s three-tiered federal polity conforms to international trends. It represents a multidimensional institutionalization of participatory democracy designed to involve the public in decision-making. Increasingly, it is a practice which displays the markers of professionalization, including (self-described) professionals, professional associations and a code of ethics. The individuals who design, communicate, and facilitate community engagement are placed in a unique position, whereas most professions claim to serve both their client or employer and a greater public good, community engagement practitioners play these roles while also claiming to serve as “guardians” of democratic processes. Yet the claimed professionalization of community engagement is raising some questions: Is community engagement really a profession – and by what criteria ought this be assessed? What tensions do community engagement practitioners face by “serving multiple masters,” and how do they manage these? More pointedly, how can ethics inform our understanding of community engagement and its professionalization? This chapter examines the case for the practice of community engagement as a profession using Noordegraaf’s (2007) pillars of pure professionalism as a guide. It then explores some practical examples of the tensions practitioners may experience. The chapter concludes by reflecting on the future direction of community engagement given its positioning