Efficient T-Cell Compartment in HIV-Positive Patients Receiving Orthotopic Liver Transplant and Immunosuppressive Therapy.

BACKGROUND: In patients undergoing orthotopic liver transplant (OLT), immunosuppressive treatment is mandatory and infections are leading causes of morbidity/mortality. Thus, it is essential to understand the functionality of cell-mediated immunity after OLT. The aim of the study was to identify changes in T-cell phenotype and polyfunctionality in human immunodeficiency virus-positive (HIV+) and -negative (HIV-) patients undergoing immunosuppressive treatment after OLT. METHODS: We studied peripheral blood mononuclear cells from 108 subjects divided into 4 groups of 27: HIV+ transplanted patients, HIV- transplanted patients, HIV+ nontransplanted patients, and healthy subjects. T-cell activation, differentiation, and cytokine production were analyzed by flow cytometry. RESULTS: Median age was 55 years (interquartile range, 52-59 years); the median CD4 count in HIV+ patients was 567 cells/mL, and all had undetectable viral load. CD4+ and CD8+ T-cell subpopulations showed different distributions between HIV+ and HIV- OLT patients. A cluster representing effector cells expressing PD1 was abundant in HIV- transplanted patients and they were characterized by higher levels of CD4+ T cells able to produce interferon-γ and tumor necrosis factor-α. CONCLUSIONS: HIV- transplanted patients have more exhausted or inflammatory T cells compared to HIV+ transplanted patients, suggesting that patients who have already experienced a form of immunosuppression due to HIV infection respond differently to anti-rejection therapy.

Impact of prolonged maraviroc treatment on non-AIDS-related comorbidities in HIV-positive patients: a retrospective cohort study.

OBJECTIVES: This retrospective study evaluates the effect of maraviroc, the first CCR5 receptor antagonist, on non-AIDS-related comorbidity incidence and its impact on inflammatory and lipid parameters. METHODS: Seventy-four HIV patients on maraviroc treatment were compared with 312 patients never exposed to maraviroc (matched for sex, age and CD4 nadir). RESULTS: At baseline (T0), maraviroc patients presented a longer duration of HIV infection, a higher prevalence of comorbidities and a greater frequency of polypharmacy. Non-AIDS-defining disease incidence was lower in the maraviroc group than in the non-maraviroc group (without achieving statistical significance). Except triglycerides (TGL), which dropped only in the maraviroc group, inflammatory and immunological parameters did not significantly change in either group by the end of the study period (T3). At T3, high-sensitivity C-reactive protein (hsCRP) and high-density lipoprotein were inversely correlated in both groups (Spearman's rho: maraviroc -0.30, P = 0.05; non-maraviroc -0.23, P = 0.0003). Only in the non-maraviroc group was the positive correlation between hsCRP and lipids observed both at T0 (hsCRP/low-density lipoprotein (LDL) +0.17, P = 0.004; hsCRP/total cholesterol +0.20, P = 0.0007; hsCRP/TGL +0.12, P = 0.04) and T3 (hsCRP/LDL +0.26, P < 0.0001; hsCRP/total cholesterol +0.24, P = 0.0001; hsCRP/TGL +0.15, P = 0.02). These correlations were not found in the maraviroc group. A significant positive correlation was found at T0 and at T3 between hsCRP and D-dimer in both groups (maraviroc: T0 +0.46, P = 0.0007; T3 +0.41, P = 0.006; non-maraviroc: T0 +0.17, P = 0.02; T3: +0.17, P = 0.017). CONCLUSIONS: These data suggest a possible protective role of maraviroc in the incidence of non-AIDS-related comorbidities in a population with longer-lasting infection and allow us to hypothesize its role in the modulation of lipid-dependent inflammation.

Compression of frailty in adults living with HIV.

BACKGROUND: Contemporary HIV care may reduce frailty in older adults living with HIV (OALWH). Objective of the study was to estimate prevalence of frailty at the age of 50 and 75 years, and build a model to quantify the burden of frailty in the year 2030. METHODS: This study included OALWH attending Modena HIV Metabolic Clinic between 2009 and 2015. Patients are referred from more than 120 HIV clinics well distributed across Italy, therefore being country representative. Our model forecasts the new entries on yearly basis up to 2030. Changes in frailty over a one-year period using a 37-variable frailty index (FI) and death rates were modelled using a validated mathematical algorithm with parameters adjusted to best represent the changes observed at the clinic. In this study, we assessed the number of frailest individuals (defined with a FI > 0.4) at the age of 50 and at the age 75 by calendar year. RESULTS: In the period 2015-2030 we model that frailest OALWH at age 50 will decrease from 26 to 7%, and at the age of 75 years will increase from 43 to 52%. This implies a shift of the frailty prevalence at an older age. CONCLUSION: We have presented projections of how the burden of frailty in older adults, living with HIV will change. We project fewer people aged 50+ with severe frailty, most of whom will be older than now. These results suggest a compression of age-related frailty.

Impact of polypharmacy on antiretroviral prescription in people living with HIV.

OBJECTIVES: To evaluate the relationship between polypharmacy and ART, delivered as conventional multi-tablet three-drug regimens, single-tablet regimens or less-drug regimens (simplified mono or dual regimens). METHODS: We conducted a cross-sectional analysis of electronic data from the prospective Modena HIV Metabolic Clinic Cohort Study. We included the last clinical observation for each patient from January 2006 to December 2015. Polypharmacy was defined as the use of five or more medications (excluding ART). Multi-morbidity was classified as the presence of two or more non-infectious comorbidities. Factors associated with different ART regimens were analysed using multivariable multinomial logistic regression analyses with multi-tablet three-drug regimens as the reference. RESULTS: A total of 2944 patients (33.7% females) were included in the analysis. Multinomial logistic regression analysis identified polypharmacy to be negatively associated with single-tablet regimens [relative risk reduction (RRR) = 0.48, 95% CI = 0.28-0.81] independently from frailty (RRR = 0.68, 95% CI = 0.59-0.78), after correction for age, gender, HIV infection duration, current and nadir CD4 and calendar year. This association was not found comparing multi-tablet three-drug regimens and less-drug regimens. CONCLUSIONS: Single-tablet regimens are less likely to be prescribed in patients with polypharmacy. Single-tablet regimens are perceived to be less flexible in patients with multi-morbidity and at higher risk of drug-drug interaction.

Prevalence and outcomes of diaphragmatic dysfunction assessed by ultrasound technology during acute exacerbation of COPD: A pilot study.

BACKGROUND AND OBJECTIVE: The prevalence and clinical consequences of diaphragmatic dysfunction (DD) during acute exacerbations of COPD (AECOPD) remain unknown. The aim of this study was (i) to evaluate the prevalence of DD as assessed by ultrasonography (US) and (ii) to report the impact of DD on non-invasive mechanical ventilation (NIV) failure, length of hospital stay and mortality in severe AECOPD admitted to respiratory intensive care unit (RICU). METHODS: Forty-one consecutive AECOPD patients with respiratory acidosis admitted over a 12-month period to the RICU of the University Hospital of Modena were studied. Diaphragmatic ultrasound (DU) was performed on admission before starting NIV. A change in diaphragmatic thickness (ΔTdi) less than 20% during spontaneous breathing was considered to confirm the presence of dysfunction (DD+). NIV failure and other clinical outcomes (duration of mechanical ventilation MV, tracheostomy, length of hospital stay and mortality) were recorded. RESULTS: A total of 10 out of 41 patients (24.3%) presented DD+, which was significantly associated with steroid use (P = 0.002, R-squared = 0.19). DD+ correlated with NIV failure (P < 0.001, R-squared = 0.27), longer intensive care unit (ICU) stay (P = 0.02, R-squared = 0.13), prolonged MV (P = 0.023, R-squared = 0.15) and need for tracheostomy (P = 0.006, R-squared = 0.20). Moreover, the Kaplan-Meyer survival estimates showed that NIV failure (log-rank test P value = 0.001, HR = 8.09 (95% CI: 2.7-24.2)) and mortality in RICU (log-rank test P value = 0.039, HR = 4.08 (95% CI: 1.0-16.4)) were significantly associated with DD+. CONCLUSION: In hospitalized AECOPD patients submitted to NIV, severe DD was seen in almost one-quarter of patients. DD may cause NIV failure, and impacts on the use of clinical resources and on the patient's short-term mortality.

A frailty index predicts post-liver transplant morbidity and mortality in HIV-positive patients.

BACKGROUND: We hypothesized that frailty acts as a measure of health outcomes in the context of LT. The aim of this study was to explore frailty index across LT, as a measure of morbidity and mortality. This was a retrospective observational study including all consecutive 47 HIV+patients who received LT in Modena, Italy from 2003 to June 2015. METHODS: frailty index (FI) was constructed from 30 health variables. It was used both as a continuous score and as a categorical variable, defining 'most frail' a FI > 0.45. FI change across transplant (deltaFI, ΔFI) was calculated as the difference between year 1 FI (FI-Y1) and pre-transplant FI (FI-t0). The outcomes measures were mortality and "otpimal LT" (defined as being alive without multi-morbidity). RESULTS: Median value of FI-t0 was 0.48 (IQR 0.42-0.52), FI-Y1 was 0.31 (IQR 0.26-0.41). At year five mortality rate was 45%, "optimal transplant" rate at year 1 was 38%. All the patients who died in the post-LT were most frail in the pre-LT. ΔFI was a predictor of mortality after correction for age and MELD (HR = 1.10, p = 0.006) and was inversely associated with optimal transplant after correction for age (HR = 1.04, p = 0.01). CONCLUSIONS: We validated FI as a valuable health measure in HIV transplant. In particular, we found a relevant correlation between FI strata at baseline and mortality and a statistically significant correlation between, ΔFI and survival rate.

Late presentation increases risk and costs of non-infectious comorbidities in people with HIV: an Italian cost impact study.

BACKGROUND: Late presentation (LP) at the time of HIV diagnosis is defined as presentation with AIDS whatever the CD4 cell count or with CD4 <350 cells/mm. The objective of our study was to assess the prevalence of non-infectious comorbidities (NICM) and multimorbidity among HIV-positive individuals with and without a history of LP (HIV + LP and HIV + EP, respectively), and compare them to matched HIV-negative control participants from a community-based cohort. The secondary objective was to provide estimates and determinants of direct cost of medical care in HIV patients. METHODS: We performed a matched cohort study including HIV + LP and HIV + EP among people attending the Modena HIV Metabolic Clinic (MHMC) in 2014. HIV-positive participants were matched in a 1:3 ratio with HIV-negative participants from the CINECA ARNO database. Multimorbidity was defined as the concurrent presence of ≥2 NICM. Logistic regression models were constructed to evaluate associated predictors of NICM and multimorbidity. RESULTS: We analyzed 452 HIV + LP and 73 HIV + EP participants in comparison to 1575 HIV-negative controls. The mean age was 46 ± 9 years, 27.5% were women. Prevalence of NICM and multimorbidity were fourfold higher in the HIV + LP compared to the general population (p < 0.001), while HIV + EP present an intermediate risk. LP was associated with increased total costs in all age strata, but appear particularly relevant in patients above 50 years of age, after adjusting for age, multimorbidity, and antiretroviral costs. CONCLUSIONS: LP with HIV infection is still very frequent in Italy, is associated with higher prevalence of NICM and multimorbidity, and contributes to higher total care costs. Encouraging early testing and access to care is still urgently needed.

Prediction of hard cardiovascular events in HIV patients.

OBJECTIVES: To assess the accuracy of risk prediction algorithms used in the general population and an HIV-specific algorithm to predict hard cardiovascular events. METHODS: We compared the pooled equation algorithm (PE) proposed by the American Heart Association with the Framingham risk score (FRS) and the HIV-specific DAD (Data Collection on Adverse Effects of Anti-HIV Drugs) algorithm in a cohort of 2550 HIV+ patients followed for 17 337 patient-years. RESULTS: During follow-up we recorded 67 myocardial infarctions and 2 cardiovascular deaths. PE and FRS identified and missed the same number of events (44 of 69 identified by PE and 49 of 69 by FRS). Similarly, DAD and FRS predicted and missed the same number of events (38 of 64 and 44 of 64 identified, respectively). All algorithms showed moderate sensitivity, specificity and positive predictive values, but high negative predictive values. However, PE and DAD identified more patients with no events than FRS (13.8% and 9.3% net reclassification improvement, respectively). CONCLUSIONS: All algorithms showed a modest predictive ability, although the PE and DAD algorithms identified more patients at low risk.

Nonalcoholic fatty liver disease is associated with an almost twofold increased risk of incident type 2 diabetes and metabolic syndrome. Evidence from a systematic review and meta-analysis.

BACKGROUND AND AIM: The magnitude of the risk of incident type 2 diabetes (T2D) and metabolic syndrome (MetS) among patients with nonalcoholic fatty liver disease (NAFLD) is poorly known. We gauged the risk of developing T2D and MetS in patients with NAFLD diagnosed by either serum liver enzymes (aminotransferases or gamma-glutamyltransferase [GGT]) or ultrasonography. METHODS: Pertinent prospective studies were identified through extensive electronic database research, and studies fulfilling enrolment criteria were included in the meta-analysis. RESULTS: Overall, in a pooled population of 117020 patients (from 20 studies), who were followed-up for a median period of 5 years (range: 3-14.7 years), NAFLD was associated with an increased risk of incident T2D with a pooled relative risk of 1.97 (95% confidence interval [CI], 1.80-2.15) for alanine aminotransferase, 1.58 (95% CI, 1.43-1.74) for aspartate aminotransferase, 1.86 (95% CI, 1.71-2.03) for GGT (last vs first quartile or quintile), and 1.86 (95% CI, 1.76-1.95) for ultrasonography, respectively. Overall, in a pooled population of 81411 patients (from eight studies) who were followed-up for a median period of 4.5 years (range: 3-11 years), NAFLD was associated with an increased risk of incident MetS with a pooled relative risk of 1.80 (95% CI, 1.72-1.89) for alanine aminotransferase (last vs first quartile or quintile), 1.98 (95% CI, 1.89-2.07) for GGT, and 3.22 (95% CI, 3.05-3.41) for ultrasonography, respectively. CONCLUSIONS: Nonalcoholic fatty liver disease, as diagnosed by either liver enzymes or ultrasonography, significantly increases the risk of incident T2D and MetS over a median 5-year follow-up.

Ultrasound assessment of diaphragmatic function in patients with amyotrophic lateral sclerosis.

BACKGROUND AND OBJECTIVE: Evaluation of diaphragm function in Amyotrophic Lateral Sclerosis (ALS) is critical in determining when to commence non-invasive mechanical ventilation (NIV). Currently, forced vital capacity (FVC) and sniff nasal inspiratory pressure (SNIP) are volitional measures for this evaluation, but require collaboration and are poorly specific. The primary aim of this study was to assess whether diaphragmatic thickness measured by ultrasound (US) correlates with lung function impairment in ALS patients. The secondary aim was then to compare US diaphragm thickness index (ΔTdi) with a new parameter (ΔTmax index). METHODS: 41 patients with ALS and 30 healthy subjects were enrolled in the study. All subjects underwent spirometry, SNIP and diaphragm US evaluation, while arterial blood gases were measured in some patients only. US assessed diaphragm thickness (Tdi) at tidal volume (Vt) or total lung capacity (TLC), and their ratio (ΔTmax) were recorded. Changes (Δ) in Tdi indices during tidal volume (ΔTdiVt) and maximal inspiration (ΔTdiTLC) were also assessed. RESULTS: ΔTdiTLC (p <0.001) and ΔTmax (p = 0.007), but not ΔTdiVt, differed between patients and controls. Significant correlation (p < 0.05) was found between ΔTdiTLC, ΔTmax and FVC. The ROC curve analysis for comparison of individual testing showed better accuracy with Δtmax than with ΔtdiTLC for FVC (AUC 0.76 and 0.27) and SNIP (AUC 0.71 and 0.25). CONCLUSION: Diaphragm thickness assessed by ultrasound significantly correlates with global respiratory alterations in patients with ALS. ΔTmax represents a new US index of early diaphragmatic dysfunction, better related with the routinely performed lung function tests.

Inverse correlation between vascular calcification and bone mineral density in human immunodeficiency virus-infected patients.

HIV-infected individuals suffer from accelerated aging, which manifests as premature cardiovascular and bone disease. However, little is known of the association of these two disorders in the HIV population. Our objective was to investigate the association between a marker of atherosclerosis (coronary artery calcium [CAC]) and low bone mineral density (BMD) in a cross-sectional cohort of HIV-infected patients. The study was conducted at the University of Modena and Reggio Emilia, Italy. A total of 636 consecutive middle-aged, HIV-infected subjects were recruited between January 2006 and December 2010. All patients underwent CAC and BMD assessment. Patients were categorized according to a CAC score <100 or >100 units based on previous literature that identified this cut-point as a marker of increased risk. Low femoral and lumbar spine BMD was defined as <25th percentile value for the study cohort. Logistic regression and bootstrap analysis were used to assess the independent association between CAC and BMD. The main outcome measure was a CAC score >100. Patients with CAC > 100 were older and more likely to be men, diabetic, and overweight. Patients with CAC < 100 had better renal function and a lower cardiovascular risk profile. After adjusting for age, sex, traditional and HIV-specific risk factors, vitamin D level, and PTH level, there was a significant association between CAC > 100 and low BMD for the femur (OR = 2.33, 95 % CI 1.09-4.99; p = 0.02) but not for the spine. Bootstrap analyses confirmed these findings. In summary, CAC was independently associated with low femoral BMD in HIV-infected patients. Future studies should test whether therapies that attenuate cardiovascular risk in HIV favorably impact bone health.

Knowledge on Parental Hesitancy toward COVID-19 Vaccination of Children 5-11 Years Old.

Although vaccines are the safest and the most effective measure to prevent disease, disability, and death from various pediatric infectious diseases, parental vaccine hesitancy is a common and increasing phenomenon worldwide. To contribute to improving our knowledge on parental willingness and hesitancy toward COVID-19 vaccine administration in children aged 5-11 years, an anonymous online questionnaire was disseminated in Italy after the COVID-19 vaccine's authorization for this age group. An online survey was conducted using the Crowd Signal platform from 15 December 2021 to 15 January 2022 in Italy among parents of children 5-11 years old. A total of 3433 questionnaires were analyzed. Overall, a "Favorable" position was observed in 1459 (42.5%) parents, a "Doubtful" one in 1223 (35.6%) and a "Hesitant/Reluctant" one in 751 (21.9%). The univariate multinomial logistic regression analysis and the multivariate multinomial logistic regression analysis showed that the Hesitant/Reluctant parents were younger than 40 years of age, mostly female, with a secondary or middle school degree, an annual income below EUR 28,000, more than one child in the age range from 5 to 11 years, an underestimated consideration of the severity of COVID-19's effects, and concern regarding the COVID-19 vaccines in general. These results show that in Italy, most parents of children aged 5 to 11 were doubtful or hesitant/reluctant to vaccinate their children against the COVID-19 virus. Poor trust in health institutions as well as poor consideration of the epidemiological and clinical relevance of COVID-19 in children seem to have played the biggest roles in forming these attitudes. Moreover, the negative attitude of several parents who previously agreed to immunize their children against other childhood illnesses according to the official national pediatric immunization schedule clearly indicates that only the COVID-19 vaccine was put in doubt or rejected. All these findings lead us to conclude that to improve COVID-19 vaccination coverage in children aged 5 to 11, health authorities should increase parental education on the true clinical relevance of COVID-19 and on the importance of its prevention to hinder the evolution of the pandemic in pediatric subjects and the emergence of new variants, and its relative weight in influencing the efficacy of vaccines.

Health surveillance for SARS-CoV-2: infection spread and vaccination coverage in the schools of Modena province, Italy.

Introduction: In Italy, over 4.8 million individuals aged 0-19 years have been infected with SARS-CoV-2. This study aims to evaluate the spread of SARS-CoV-2 within schools in Modena province and the influence of anti-SARS-CoV-2 vaccination coverage. Methods: We performed a survey in the period 1 September-15 December 2021, involving student population aged 0-19 years and related teachers screened for SARS-CoV-2 infection using nasopharyngeal swab after the detection of an index case within their class. During the study period, vaccination against SARS-CoV-2 was actively offered to all subjects aged ≥12 years. Results: A total of 13,934 subjects were tested, 12,534 students and 1,400 teachers (594 classes). We identified a total of 594 and 779 index and secondary cases, respectively. We found that 9.8% of students and 10.6% of teachers were positive for SARS-CoV-2. Overall at the test time, 32.5% were vaccinated with at least one dose of anti-SARS-CoV-2 vaccine. Among secondary cases, 7.8% were vaccinated compared to 34.9% among negative tested subjects. A higher secondary attack rate was for non-vaccinated subjects rather than vaccinated ones (8.1% vs. 1.4%). Higher secondary attack rates were reported for subjects attending infant and primary school (5.9 and 9.6%, respectively). Lower secondary attack rates were for those who attended middle school (4.9%) and especially high school (1.7%). Conclusion: Our results highlight the differential spread of the infection within various educational settings and that the vaccination, available in the study period for the population aged ≥12, have mitigated SARS-CoV-2 spread in high and middle schools.

Parallel increase of subclinical atherosclerosis and epicardial adipose tissue in patients with HIV.

BACKGROUND: Epicardial adipose tissue (EAT) may contribute to the development of coronary atherosclerosis via paracrine secretion of inflammatory cytokines. METHODS: This is a prospective, observational study of 240 consecutive HIV-infected patients receiving antiretroviral therapy. All patients underwent 2 sequential chest computed tomographic scans to assess the change in coronary artery calcium (CAC), a marker of subclinical atherosclerosis, and EAT volume. Patients with known cardiovascular disease were excluded. Factors independently associated with EAT change were explored using multivariable linear regression analyses. The association between EAT increase and CAC progression was explored using logistic regression analyses. RESULTS: Two hundred forty patients were included. Patients' mean age was 47.5 ± 8 years, and 68% were men. The median interval between computed tomographic scans was 18.7 months (interquartile range 10-27 months). Men showed a larger increase in EAT (5 ± 14.2 cm(3)) than did women (-0.45 ± 8.8 cm(3), P = .007). Factors independently associated with change in EAT were CD4(+) recovery (ß = 0.43, CI 0.05-0.82) and male gender (ß = 5.65, CI, 1.05-10.26). Change in EAT was independently associated with CAC progression (odds ratio 1.04, 95% CI 1.004-1.88, P = .030) after adjusting for traditional cardiovascular risk factors. CONCLUSIONS: In this cohort of patients with HIV receiving antiretroviral therapy, male gender and CD4(+) were independent predictors of EAT increase, and there was a parallel progression of CAC and EAT. Abnormal immunoreactivity associated with T-lymphocyte recovery should be further studied as a determinant of atherosclerosis progression in HIV-infected patients.

Erectile dysfunction is more common in young to middle-aged HIV-infected men than in HIV-uninfected men.

INTRODUCTION: Erectile dysfunction (ED) is common among elderly men and patients suffering from chronic diseases, the latter probably including also HIV infection. No studies, however, compared the prevalence of ED in HIV-infected and HIV-uninfected individuals using the international index of erectile function (IIEF-15). AIM: The aim of this study is to compare ED prevalence in young to middle-aged men with and without HIV infection using the IIEF-15 questionnaire. METHODS: We conducted a cross-sectional, observational, controlled study on 444 HIV-infected men and 71 HIV-uninfected men. MAIN OUTCOMES MEASURES: The IIEF-15 questionnaire was used to assess ED. A cutoff score of ≤25 of the erectile domain was used to diagnose ED. Serum testosterone, demographic, and anthropometric (weight, height, and body mass index [BMI]) characteristics were obtained from all participants. Statistics included the T-test, the Fisher's test, univariable and multivariable logistic regression, and univariate and multivariate Spearman's correlation analysis. RESULTS: The HIV-uninfected group was significantly younger than the HIV-infected group and presented a higher BMI (P < 0.001). The prevalence of mild, moderate, and severe ED was higher in HIV-infected men than in HIV-uninfected men of all decades of age. In univariate analysis, HIV infection was associated with ED (odds ratio [OR] = 34.19, P < 0.001). In multivariable logistic regression analysis, HIV infection remained the strongest predictors of ED (OR = 42.26, P < 0.001) followed by hypogonadism, after adjusting for age and BMI. CONCLUSIONS: This study demonstrates a clear association between ED and HIV infection, after adjusting for age and BMI. Other than HIV infection, hypogonadism was associated with ED. In addition, the prevalence of ED was higher in HIV-infected men than in HIV-uninfected men, in all decades of age. The early onset of ED in HIV-infected men could be considered a peculiar clinical hallmark of HIV and confirms precocious aging in these patients. ED should be of concern to clinicians when managing HIV-infected men even if the latter are young or middle aged.

Erectile dysfunction is not a mirror of endothelial dysfunction in HIV-infected patients.

INTRODUCTION: The penis has been compared to a barometer of endothelial health, erectile dysfunction (ED) being an early sign of endothelial dysfunction. AIM: The aim of the study was to investigate the extent of the association between ED and endothelial dysfunction in patients with human immunodeficiency virus (HIV) infection on antiretroviral therapy. METHODS: In this observational cross-sectional study, we evaluated the prevalence and factors associated with ED in a cohort of 133 HIV-infected men. MAIN OUTCOME MEASURES: The International Index of Erectile Function, ultrasound assessment of brachial artery flow mediated dilatation (FMD), and multi-slice computed tomography for coronary artery calcifications (CAC) as surrogates of endothelial dysfunction, the Adult Treatment Panel III criteria to diagnose metabolic syndrome (MS), plasma total testosterone (hypogonadism), and a visual analogue scale (VAS) of aesthetic satisfaction of the face and of the body (psychological distress associated with lipodystrophy). RESULTS: Thirty-nine (29.32%) patients had mild ED, 14 (10.52%) patients had moderate ED, and 26 (19.55%) patients had severe ED. Prevalence of ED ranged from 45% to 65%, respectively, in patients less than 40 and more than 60 years old. MS was present in 20 (25%) patients with ED and 13 (24%) patients without ED (P value = 0.87). Prevalence of ED neither appeared to be associated with MS as a single clinical pathological entity nor with the numbers of its diagnostic components. FMD < 7% was present in 25 (32%) patients with ED and 18 (33%) patients without ED (P value = 0.83), and CAC > 100 was present in 8 (10%) patients with ED and 5 (9%) patients without ED (P value = 0.87). A stepwise multivariable logistic regression analysis was used to find predictors of ED. Independent predictors were VAS face (odds ratio [OR] = 0.85, 95% confidence interval [CI] 0.73-0.99, P = 0.049) and age per 10 years of increase (OR = 1.73, 95% CI 1.02-2.94, P = 0.04). CONCLUSIONS: Age constituted the most important risk factor for ED, which was related to aesthetic dissatisfaction of the face leading to negative body image perception.

Long COVID in Children and Adolescents.

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) has caused significant mortality and morbidity worldwide. In children, the acute SARS-CoV-2 infection is often asymptomatic or paucisymptomatic, and life-threatening complications are rare. Nevertheless, there are two long-term consequences of SARS-CoV-2 infection in children that raise concern: multisystem inflammatory syndrome in children (MIS-C) and long COVID. While the understanding and the experience regarding the acute phase of SARS-CoV-2 infection have remarkably increased over time, scientific and clinical research is still exploring the long-term effects of COVID-19. In children, data on long COVID are scant. Reports are conflicting regarding its prevalence, duration and impact on daily life. This narrative review explored the latest literature regarding long COVID-19 in the pediatric population. We showed that long COVID in children might be a relevant clinical problem. In most cases, the prognosis is good, but some children may develop long-term symptoms with a significant impact on their daily life. The paucity of studies on long COVID, including a control group of children not infected by SARS-CoV-2, prevents us from drawing firm conclusions. Whether the neuropsychiatric symptoms widely observed in children and adolescents with long COVID are the consequence of SARS-CoV-2 infection or are due to the tremendous stress resulting from the restrictions and the pandemics is still not clear. In both cases, psychological support can play a fundamental role in managing COVID pandemics in children. More knowledge is needed to share a standardized definition of the syndrome and improve its management and treatment.

Italian intersociety consensus on management of long covid in children.

BACKGROUND: Two sequelae of pediatric COVID-19 have been identified, the multisystem inflammatory syndrome in children (MIS-C) and the long COVID. Long COVID is much less precisely defined and includes all the persistent or new clinical manifestations evidenced in subjects previously infected by SARS-CoV-2 beyond the period of the acute infection and that cannot be explained by an alternative diagnosis. In this Intersociety Consensus, present knowledge on pediatric long COVID as well as how to identify and manage children with long COVID are discussed. MAIN FINDINGS: Although the true prevalence of long COVID in pediatrics is not exactly determined, it seems appropriate to recommend evaluating the presence of symptoms suggestive of long COVID near the end of the acute phase of the disease, between 4 and 12 weeks from this. Long COVID in children and adolescents should be suspected in presence of persistent headache and fatigue, sleep disturbance, difficulty in concentrating, abdominal pain, myalgia or arthralgia. Persistent chest pain, stomach pain, diarrhea, heart palpitations, and skin lesions should be considered as possible symptoms of long COVID. It is recommended that the primary care pediatrician visits all subjects with a suspected or a proven diagnosis of SARS-CoV-2 infection after 4 weeks to check for the presence of symptoms of previously unknown disease. In any case, a further check-up by the primary care pediatrician should be scheduled 3 months after the diagnosis of SARS-CoV-2 infection to confirm normality or to address emerging problems. The subjects who present symptoms of any organic problem must undergo a thorough evaluation of the same, with a possible request for clinical, laboratory and / or radiological in-depth analysis in case of need. Children and adolescents with clear symptoms of mental stress will need to be followed up by existing local services for problems of this type. CONCLUSIONS: Pediatric long COVID is a relevant problem that involve a considerable proportion of children and adolescents. Prognosis of these cases is generally good as in most of them symptoms disappear spontaneously. The few children with significant medical problems should be early identified after the acute phase of the infection and adequately managed to assure complete resolution. A relevant psychological support for all the children during COVID-19 pandemic must be organized by health authorities and government that have to treat this as a public health issue.

Premature age-related comorbidities among HIV-infected persons compared with the general population.

BACKGROUND: Human immunodeficiency virus (HIV)-infected patients may have a greater risk of noninfectious comorbidities (NICMs) compared with the general population. We assessed the prevalence and risk factors for NICMs in a large cohort of HIV-infected adults and compared these findings with data from matched control subjects. METHODS: We performed a case-control study involving antiretroviral therapy (ART)-experienced HIV-infected patients treated at Modena University, Italy, from 2002 through 2009. These patients were compared with age-, sex-, and race-matched adults (control subjects) from the general population included in the CINECA ARNO database. NICMs included cardiovascular disease, hypertension, diabetes mellitus, bone fractures, and renal failure. Polypathology (Pp) was defined as the concurrent presence of ≥2 NICMs. Logistic regression models were constructed to evaluate associated predictors of NICMs and Pp. RESULTS: There were 2854 patients and 8562 control subjects. The mean age was 46 years, and 37% were women. Individual NICM and Pp prevalences in each age stratum were higher among patients than among controls (all P <.001). Pp prevalence among patients aged 41-50 years was similar to that among controls aged 51-60 years (P value was not statistically significant); diabetes mellitus, cardiovascular disease, bone fractures, and renal failure were statistically independent after adjustment for sex, age, and hypertension. Logistic regression models showed that independent predictors of Pp in the overall cohort were (all P < .001) age (odds ratio [OR], 1.11), male sex (OR, 1.77), nadir CD4 cell count <200 cells/µL (OR, 4.46), and ART exposure (OR, 1.01). CONCLUSIONS: Specific age-related NICMs and Pp were more common among HIV-infected patients than in the general population. The prevalence of Pp in HIV-infected persons anticipated Pp prevalence observed in the general population among persons who were 10 years older, and HIV-specific cofactors (lower nadir CD4 cell count and more prolonged ART exposure) were identified as risk factors. These data support the need for earlier screening for NICMs in HIV-infected patients.

Human immunodeficiency virus infection is associated with accelerated atherosclerosis.

OBJECTIVES: Cardiovascular risk is increased in HIV-infected individuals compared with the general population, making HIV disease an ideal model to investigate the pathogenesis and natural history of atherosclerosis. In this pilot study, we compared the progression of coronary artery calcium (CAC) between HIV-infected and uninfected patients. METHODS: Atherosclerosis progression was assessed in 25 HIV-infected men and 13 HIV-negative controls by means of sequential CAC scans using CT. A CAC score progression ≥ 15%/year was used as a surrogate marker of increased risk of cardiovascular events. RESULTS: During a median follow-up of 11 months, a CAC score increase ≥ 15%/year was detected in 14 HIV-infected patients (56%) and 4 HIV-negative individuals (31%). HIV infection, age and hypercholesterolaemia were independently associated with a CAC score increase ≥ 15%/year in an adjusted Cox regression model. CONCLUSIONS: HIV infection, age and hypercholesterolaemia were independently associated with CAC progression. HIV as well as traditional risk factors contribute to accelerate atherosclerosis in HIV-infected patients.