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.

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.

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.

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.

Anti-COVID Vaccination for Adolescents: A Survey on Determinants of Vaccine Parental Hesitancy.

Vaccine hesitancy has been considered one of the most severe threats to global health, as it represents an obstacle to achieving adequate vaccination coverage. Recent research studies aimed at investigating the propensity for anti-COVID vaccination among adults have found a high prevalence of vaccine hesitancy, but few data are available on parental vaccine hesitancy. We therefore built an anonymous online survey to investigate the factors related to the vaccine hesitancy of parents of adolescents between 12 and 17 years of age, with a special focus on demographic factors and the domains of confidence and complacency. The online survey was conducted by using the Crowd Signal platform from 15 July to 16 August 2021, in Italy. A total of 1799 analyzable questionnaires were analyzed. Overall, Favorable and Doubtful parents declared a higher level of confidence on safety and efficacy of pediatric vaccines and on confidence in health institutions than Hesitant/Reluctant ones (p-values < 0.001). 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, with a secondary-school or three-year degree, free-lance, with a family income below €28,000, with an erroneous perception of the risk of COVID-19 as disease and with fear of anti-COVID vaccination. These results, which should be confirmed in a larger population and in different geographical areas, should lead Institutions and stakeholders to identify targeted communication tools to improve trust in health institutions, especially by younger parents.

Use of Monoclonal Antibody to Treat COVID-19 in Children and Adolescents: Risk of Abuse of Prescription and Exacerbation of Health Inequalities.

Monoclonal antibodies (mAbs) that neutralize SARS-CoV-2 in infected patients are a new class of antiviral agents approved as a type of passive immunotherapy. They should be administered to adults and children (≥12 years old, weighing ≥ 40 kg) with SARS-CoV-2 positivity, and who are suffering from a chronic underlying disease and are at risk of severe COVID-19 and/or hospitalization. The aim of this manuscript is to discuss the benefit-to-risk of mAb therapy to treat COVID-19 in pediatric age, according to current reports. A problem is that the authorization for mAbs use in children was given without studies previously evaluating the efficacy, safety and tolerability of mAbs in pediatric patients. Moreover, although the total number of children with chronic severe underlying disease is not marginal, the risk of severe COVID-19 in pediatric age is significantly reduced than in adults and the role of chronic underlying disease as a risk factor of severe COVID-19 development in pediatric patients is far from being precisely defined. In addition, criteria presently suggested for use of mAbs in children and adolescents are very broad and may cause individual clinicians or institutions to recommend these agents on a case-by-case basis, with an abuse in mAbs prescriptions and an exacerbation of health inequalities while resources are scarce. Several questions need to be addressed before their routine use in clinical practice, including what is their associated benefit-to-risk ratio in children and adolescents, who are the patients that could really have benefit from their use, and if there is any interference of mAb therapy on recommended vaccines. While we wait for answers to these questions from well-conducted research, an effective and safe COVID-19 vaccine for vulnerable pediatric patients remains the best strategy to prevent COVID-19 and represents the priority for public health policies.

COVID-19 Management in the Pediatric Age: Consensus Document of the COVID-19 Working Group in Paediatrics of the Emilia-Romagna Region (RE-CO-Ped), Italy.

Since December 2019, coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread, becoming the first pandemic of the 21st century by number of deaths (over 2,000,000 worldwide). Many aspects of SARS-CoV-2 infection in children and adolescents remain unclear, and optimal treatment has not yet been defined. Therefore, our goal was to develop a consensus document, practically synthesizing the accumulated data and clinical experience of our expert group. Literature research was carried out using the keywords "COVID-19" or "SARS-CoV-2" and "children" or "pediatrics" and "prevention" or "diagnosis" or "MIS-C" or "treatment" in electronic databases (MEDLINE, PUBMED), existing guidelines and gray literature. The fact that the majority of the problems posed by SARS-CoV-2 infection in pediatric age do not need hospital care and that, therefore, infected children and adolescents can be managed at home highlights the need for a strengthening of territorial pediatric structures. The sharing of hospitalization and therapeutic management criteria for severe cases between professionals is essential to ensure a fair approach based on the best available knowledge. Moreover, the activity of social and health professionals must also include the description, management and limitation of psychophysical-relational damage resulting from the SARS-CoV-2 pandemic on the health of children and adolescents, whether or not affected by COVID-19. Due to the characteristics of COVID-19 pathology in pediatric age, the importance of strengthening the network between hospital and territorial pediatrics, school, educational, social and family personnel both for strictly clinical management and for the reduction in discomfort, with priority in children of more frail families, represents a priority.

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.

Epidemiology and Risk Factors Associated With Mortality in Consecutive Patients With Bacterial Bloodstream Infection: Impact of MDR and XDR Bacteria.

BACKGROUND: Mortality related to bloodstream infections (BSIs) is high. The epidemiology of BSIs is changing due to the increase in multidrug resistance, and it is unclear whether the presence of multidrug-resistant (MDR) organisms, per se, is an independent risk factor for mortality. Our objectives were, first, to describe the epidemiology and outcome of BSIs and, second, to determine the risk factors associated with mortality among patients with BSI. METHODS: This research used a single-center retrospective observational study design. Patients were identified through microbiological reports. Data on medical history, clinical condition, bacteria, antimicrobial therapy, and mortality were collected. The primary outcome was crude mortality at 30 days. The relationships between mortality and demographic, clinical, and microbiological variables were analyzed by multivariate analysis. RESULTS: A total of 1049 inpatients were included. MDR bacteria were isolated in 27.83% of patients, where 2.14% corresponded to an extremely drug-resistant (XDR) isolate. The crude mortality rates at days 7, 30, and 90 were 12.11%, 25.17%, and 36.13%, respectively. Pitt score >2, lung and abdomen as site of infection, and XDR Pseudomonas aeruginosa were independent risk factors for 7-, 30-, and 90-day mortality. Charlson score >4, carbapenem-resistant Klebsiella pneumoniae, and XDR Acinetobacter baumannii were independent risk factors for 30- and 90-day mortality. Infection by XDR gram-negative bacteria, Charlson score >4, and immunosuppression were independent risk factors for mortality in patients who were stable at the time of BSI. CONCLUSIONS: BSI is an event with an extreme impact on mortality. Patients with severe clinical condition are at higher risk of death. The presence of XDR gram-negative bacteria in blood is strongly and independently associated with patient death.

Epidemiology and Outcomes of Bloodstream Infections in HIV-Patients during a 13-Year Period.

No data on antibiotic resistance in bloodstream infection (BSI) in people living with HIV (PLWH) exist. The objective of this study was to describe BSI epidemiology in PLWH focusing on multidrug resistant (MDR) organisms. A retrospective, single-center, observational study was conducted including all positive blood isolates in PLWH from 2004 to 2017. Univariable and multivariable GEE models using binomial distribution family were created to evaluate the association between MDR and mortality risk. In total, 263 episodes (299 isolates) from 164 patients were analyzed; 126 (48%) BSI were community-acquired, 137 (52%) hospital-acquired. At diagnosis, 34.7% of the patients had virological failure, median CD4 count was 207/µL. Thirty- and 90-day mortality rates were 24.2% and 32.4%, respectively. Thirty- and 90-day mortality rates for MDR isolates were 33.3% and 46.9%, respectively (p < 0.05). Enterobacteriaceae were the most prevalent microorganisms (29.8%), followed by Coagulase-negative staphylococci (21.4%), and S. aureus (12.7%). In BSI due to MDR organisms, carbapenem-resistant K. pneumoniae and methicillin-resistant S. aureus were associated with mortality after adjustment for age, although this correlation was not confirmed after further adjustment for CD4 < 200/µL. In conclusion, BSI in PLWH is still a major problem in the combination antiretroviral treatment era and it is related to a poor viro-immunological status, posing the question of whether it should be considered as an AIDS-defining event.

Thymus Imaging Detection and Size Is Inversely Associated With Metabolic Syndrome and Frailty in People With HIV.

BACKGROUND: People with HIV (PWH) may experience accentuating aging in relation to immuno-activation. Little is known regarding thymus (THY) involution in this process. We sought to investigate the relationship between THY imaging detection/size and clinically relevant aging outcomes such as metabolic syndrome (MetS), multimorbidity (MM), and frailty in PWH. METHODS: This was a cross-sectional observational study including 665 HIV patients (81% males; median age, 53 years) attending Modena HIV Metabolic Clinic from 2014 to 2017. They underwent thoracic computed tomography scan as part of the medical assessment for cardiovascular disease, in which THY detection and size were reported using a semiquantitative score. Outcome measures were MetS, MM, and frailty. RESULTS: THY was detected in 27.0% of subjects; 71.1% showed THY size of grade 1-2, and 28.9% exhibited grade ≥3. Covariates that inversely correlated with THY detection were age, male gender, body mass index (BMI), and HIV duration. Covariates that inversely correlated with MetS were age, HIV duration, BMI, and THY grade 1-2. Covariates that inversely correlated with MM were age, HIV duration, and CD4 nadir. Covariates that inversely correlated with frailty were age, HIV duration, CD4 nadir, BMI, and THY detection. CONCLUSIONS: THY is inversely associated with MetS and frailty in PWH.

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 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.

The dynamic association between Frailty, CD4 and CD4/CD8 ratio in people aging with HIV.

OBJECTIVE: To investigate the association between current CD4+ T-cell count and CD4/CD8+ ratio with severity of frailty among people aging with HIV. METHODS: Cross-sectional observational study analysing data from all study visits in the ongoing prospective Modena HIV Metabolic Clinic Cohort between 2006 and 2015. Frailty severity was assessed using a frailty index (FI). We visualized the relationships between frailty index score and current CD4 cell count and CD4/CD8 ratio on two different curves adjusted for age, sex, and duration of HIV infection. RESULTS: Frailty index scores exhibited an inverse relationship with current CD4 count, up to 900 cells/µL. The CD4/CD8 ratio was inversely correlated with frailty index both below and above the cut-off of 900 CD4 cells/µL. CONCLUSIONS: Frailty in PLWH is inversely associated with both immune-activation, depicted by CD4/CD8 ratio and immune-deficit depicted by CD4 count. The first association shows a linear shape while the second shows a hook-shape with a turning point at 900 cells. Above this cut off level CD4 do not represent a significant risk factor for frailty.

Predictors of transitions in frailty severity and mortality among people aging with HIV.

BACKGROUND: People aging with HIV show variable health trajectories. Our objective was to identify longitudinal predictors of frailty severity and mortality among a group aging with HIV. METHODS: Exploratory analyses employing a multistate transition model, with data from the prospective Modena HIV Metabolic Clinic Cohort Study, based in Northern Italy, begun in 2004. Participants were followed over four years from their first available visit. We included all 963 participants (mean age 46.8±7.1; 29% female; 89% undetectable HIV viral load; median current CD4 count 549, IQR 405-720; nadir CD4 count 180, 81-280) with four-year data. Frailty was quantified using a 31-item frailty index. Outcomes were frailty index score or mortality at four-year follow-up. Candidate predictor variables were baseline frailty index score, demographic (age, sex), HIV-disease related (undetectable HIV viral load, current CD4+ T-cell count, nadir CD4 count, duration of HIV infection, and duration of antiretroviral therapy [ARV] exposure), and behavioral factors (smoking, injection drug use (IDU), and hepatitis C virus co-infection). RESULTS: Four-year mortality was 3.0% (n = 29). In multivariable analyses, independent predictors of frailty index at follow-up were baseline frailty index (RR 1.06, 95% CI 1.05-1.07), female sex (RR 0.93, 95% CI 0.87-0.98), nadir CD4 cell count (RR 0.96, 95% CI 0.93-0.99), duration of HIV infection (RR 1.06, 95% CI 1.01-1.12), duration of ARV exposure (RR 1.08, 95% CI 1.02-1.14), and smoking pack-years (1.03, 1.01-1.05). Independent predictors of mortality were baseline frailty index (OR 1.19, 1.02-1.38), current CD4 count (0.34, 0.20-0.60), and IDU (2.89, 1.30-6.42). CONCLUSIONS: Demographic, HIV-disease related, and social and behavioral factors appear to confer risk for changes in frailty severity and mortality among people aging with HIV.

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.

Clinical Utility of Epstein-Barr Virus Viral Load Monitoring and Risk Factors for Posttransplant Lymphoproliferative Disorders After Kidney Transplantation: A Single-Center, 10-Year Observational Cohort Study.

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is an important cause of morbidity and mortality in solid organ transplants. Epstein Barr virus (EBV) plays a major role in PTLD development. Guidelines recommend EBV viral load (VL) monitoring in high-risk populations in the first year. METHODS: Retrospective observational study in all adult patients who had at least 1 EBV-VL performed in the postkidney transplant (KT) period from January 2005 to December 2014 at the Policlinico Modena Hospital. We compared patients with negative EBV-DNA to patients with positive EBV-DNA and we described PTLD developed in the study period. RESULTS: One hundred ninety (36.3%) KT patients of 523 were screened for EBV-DNA with 796 samples. One hundred twenty-eight (67.4%) of 190 tested patients presented at least 1 positive sample for EBV. Older age, the use of sirolimus, everolimus, and steroids were associated with EBV-DNA positivity in the univariate analysis. Nine (1.7%) of 523 patients had PTLD. Incidence rate of PTLD in the KT cohort was 0.19/100 person year follow-up (95% confidence interval, 0.09-0.37). One of 9 patients developed early PTLD and was a high-risk patient. Only this PTLD case was positive for EBV. No PTLD case had an EBV-VL superior to 4000 copies/mL. CONCLUSIONS: Our results suggest that the keystone of PTLD diagnosis is the clinical suspicion. Our study suggests that, in line with guidelines, EBV-VL assays may be avoided in low-risk patients in the absence of a strong clinical PTLD suspicion without increasing patients' risk of developing PTLD. This represents a safe and cost-saving clinical strategy for our center.

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.

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.

Pituitary growth hormone (GH) secretion is partially rescued in HIV-infected patients with GH deficiency (GHD) compared to hypopituitary patients.

Biochemical growth hormone deficiency is prevalent among human immunodeficiency virus-infected patients, but if this condition is clinically relevant remains challenging. The aim is to prospectively compare the growth hormone deficiency/insulin-like growth factor-1 status of 71 human immunodeficiency virus-infected patients with impaired growth hormone response to growth hormone releasing hormone + Arginine with that of 65 hypopituitary patients affected by a true growth hormone deficiency secondary to pituitary disease. The main outcomes were: basal serum growth hormone, insulin-like growth factor-1, insulin-like growth factor binding protein 3, growth hormone peak and area under the curve after growth hormone response to growth hormone releasing hormone + Arginine test, body mass index, waist and hip circumference, and body composition by dual energy X-ray absorptiometry. Insulin-like growth factor-1 binding protein 3, basal growth hormone (p < 0.005), growth hormone peak and area under the curve after growth hormone response to growth hormone releasing hormone + Arginine, waist to hip ratio, insulin-like growth factor-1, fasting glucose, insulin, and triglycerides (p < 0.0001) were lower in hypopituitary than human immunodeficiency virus-infected patients. Total and trunk fat mass by dual energy X-ray absorptiometry were higher in hypopituitary than in human immunodeficiency virus-infected patients (p < 0.0001). In all the patients total body fat was associated with both growth hormone peak and area under the curve at stepwise linear regression analysis. The degree of growth hormone deficiency is more severe in hypopituitary than in human immunodeficiency virus-infected patients, suggesting that the function of growth hormone/insulin-like growth factor-1 axis is partially rescued in the latter thanks to a preserved pituitary secretory reserve. Data from the current study suggest that human immunodeficiency virus-infected patients with peak growth hormone < 9 mg/L may have partial growth hormone deficiency and clinicians should be cautious before prescribing recombinant human growth hormone replacement treatment to patients living with human immunodeficiency virus.