Humoral and cell-mediated immune responses after a booster dose of HBV vaccine in HIV-infected children, adolescents and young adults

OBJECTIVE: HBV vaccine induces protective antibodies only in 23-56% of HIV-infected children. The aim of our study is to evaluate the immunologic effects of a booster dose of HBV vaccine in HIV-infected youth. DESIGN: 53 young HIV-infected patients in whom HBV vaccination did not elicit protective Ab titers were enrolled. All patients were on ART with optimal immunological and viral response. METHOD: All patients received a booster dose of HBV vaccine (HBVAXPRO 10 \u3bcg i.m.). HBV-specific Ab titer, viral load and CD4+ T cells were measured at baseline (T0), T1, T6 and T12 months. In a subgroup of 16 patients HBV-specific cell mediated immune responses were evaluated at baseline, at T1 and T6. RESULTS: The booster dose induced seroconversion in 51% of patients at T1, 57% at T6, and49% at T12; seroconversion rate was significantly correlated with CD4+T cells at T0 and to the CD4 nadir. The booster dose induced HBV-specific cell mediated immunity at T6 mainly in Responders (Rs): Effector Memory CD8+T cells, HBV-specific TNF\u3b1-, IFN\u3b3-, granzyme secreting CD8+ T cells and IL2-secreting CD4+ T cells were significantly increased in Rs compared to T0. In Non Responders (NRs), HBV-specific IL2-secreting CD4+ T cells, Central and Effector Memory CD8+ T cells were the only parameters modified at T6. CONCLUSIONS: Seroconversion induced by a booster dose of vaccine correlates with the development of T cell immunological memory in HIV-infected patients who did not respond to the standard immunization. Alternate immunization schedules need to be considered in NRs

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Ceremonial plant consumption at Middle Bronze Age Büklükale, Kırıkkale Province, central Turkey

A shaft-like room at the Middle Bronze Age site of Büklükale in central Turkey preserved a rich archaeobotanical assemblage of charred and mineralised plant remains, dominated by fruits, spices and nuts mixed with probable bread and wood charcoals. The remains were recovered in association with numerous ceramic vessels, jewellery and exotic artefacts. We combine identification and analysis of the seeds and wood charcoals contained in this deposit with studies of Old Assyrian and Hittite textual records to investigate the circumstances of the assemblage’s formation and its significance for further understanding trade and plant consumption in Bronze Age Anatolia. We present the earliest archaeobotanical example in the region of rare and exotic plant species being consumed in the context of one or more social gatherings, including those possibly linked to ceremonial or ritual events. This offers new insights into the role of plants in the economic and social life of the southwest Asian Bronze Age, as well as the role of commensality and feasting in early states

Switching to integrase inhibitors unlinked to weight increase in perinatally HIV-infected young adults and adolescents: A 10-year observational study

An unexpected increase in weight gain has recently been reported in the course of integrase strand transfer inhibitors (INSTI) treatment. The possibility of this effect in people who are perinatally infected with HIV (PHIV) and thus exposed to lifelong therapy needs to be explored. This is a retrospective multicenter case-control study. Adults with PHIV followed between 2010 and 2019 in two outpatient services in Northern Italy were included if they had at least two weight measures in two successive years of observation. Patients were considered as cases if they were switched to INSTI (INSTI group), or controls if they were never exposed to INSTI (non-INSTI group). The date of the switch in cases was considered to be the baseline (T0), while it was randomly selected in controls. Mixed effect models were used to assess the weight changes in INSTI and non-INSTI groups. A total of 66 participants, 50.0% women, 92.4% Caucasian, were included. Median follow-up was 9 years (range 2\u201310): 4 years (range 1\u20138) before and 3 (range 1\u20139) after-T0 . Mean age at the last study visit was 27.3 (\ub14.8) years, and mean CD4+ T-cells were 820.8 (\ub1323.6) cells/mm3 . Forty-five patients were switched to INSTI during the study, while 21 remained in the non-INSTI group. The INSTI group experienced a mean increase (pre-post T0) in bodyweight of 0.28 kg/year (95% CI 12 0.29; 0.85, p = 0.338), while in the non-INSTI group, the mean increase was 0.36 kg/year (95% CI 12 0.47; 1.20, p = 0.391), without a significant difference between groups (p for interaction between time and treatment regimen = 0.868). Among patients on INSTI, the weight gain after T0 was higher than pre-T0, amounting to +0.28 kg/year (95% CI 12 0.29; 0.85), although this difference did not reach significance (p = 0.337). PHIV switched to an INSTI-based regimen did not experience an excessive weight gain compared to those who were treated with a non-INSTI based regimen in our cohort

Immunological response after a booster dose of HBV vaccine in HIV-infected youth

Background: Three doses of vaccine against HBV induce the production of protective antibody (Ab) levels (>10 IU/mL) in 95-100 % of healthy children but in only 23-56% of HIV-infected children. Ab titer elicited by vaccination decreases over time in both populations with a faster slope observed in HIV+. This decline protection against HBV is known to last almost three decades after vaccination in immunocompetent children, these data are limited in HIV+ children Methods: 53 HIV+ patients (aged 8-25 years old) in whom HBV vaccination according the Italian schedule did not elicit the generation of protective Ab titers were enrolled in the study at Paediatric Infectious Diseases Unit, L. Sacco Hospital, University of Milan. All patients had undergone ART for at least 1 year; HIV viral load was undetectable in all of them, median CD4+ count 718 mm3. All patients received a booster dose of HBV vaccine (HBVAXPRO 10 micrograms i.m.). HBV-specific Ab titer, viral load and CD4 + were measured in all subjects at baseline (T0), at 1 (T1), 6 (T6) and 12 (T12) months after the booster dose. In a subgroup of 16 patients HBV-specific cell mediated immune (CMI) responses were evaluated at baseline and at T6. Results: The booster HBV vaccine dose resulted in a seroconversion rate (anti-HBs 65 10 IU/mL) in 51% of patients at T1, 57% at T6 and 49% at T12; seroconversion rate was significantly correlated with CD4+T lymphocyte counts at T0 and to CD4 nadir (p10 IU/mL) and 5 non-responders (HBsAb <10 IU/mL). Upregulation of HBV-specific CMI compared to baseline values was observed at T6 in responders alone. Memory (p= 0.007), Effector Memory (p= 0.003), TNF\uf061- (p= 0.041), IFN\uf067- (p= 0.004), and granzyme-secreting CD8+ T cells (p= 0.003), Central Memory (p= 0.005) and IL2-secreting CD4+ T cells (p= 0.015) were significantly increased in responders compared to baseline values. Activated CD8+CD38+CD45RO+ T cells (p= 0.004) were significantly reduced as well at T6 in these individuals. No significant differences were observed when T0 and T6 data were compared in non responders. Conclusions: In HIV+ patients no responding to the standard HBV immunization protocol, seroconversion induced by a booster dose of vaccine (Ab titers <10 IU/mL) correlates with the development of T cell immunological memory. Alternate immunization schedules should be designed for those individuals who don't respond even to a booster dose of vaccin

Saliva molecular testing for sars-cov-2 surveillance in two italian primary schools

Background: No evidence has so far proven a significant role of schools in SARS-CoV-2 transmission, while the negative effects of their closure on children and adolescents are well documented. Surveillance, by means of frequent students and staff testing, has been advocated in order to implement school safety. Our aim was to report the results of a school surveillance program for the early detection of SARS-CoV-2 infection in pre- and asymptomatic subjects, by means of molecular salivary testing (MST). Methods: School surveillance in two schools in Milan, Italy, was carried out for six weeks. Each participant received a saliva collection kit, to be self-performed. Results: 401 students and 12 teachers were enrolled, and 5 positive children in 5 different classes were observed. All the cases were asymptomatic. Their nasopharyngeal swab was positive on the same day in four cases, while in one case it resulted negative on the same day and positive 3 days later. In one positive case, the whole family was set under surveillance. The positive child did not develop symptoms and no family member was infected. Conclusions: MST might represent an efficient way to actively survey communities in order to detect asymptomatic cases, thus limiting SARS-CoV-2 transmission

Efficacy of Sofosbuvir/Ledipasvir in Adolescents With Chronic Hepatitis C Genotypes 1, 3, and 4: A Real-world Study

OBJECTIVES: Sofosbuvir/Ledipasvir (SOF/LDV) has been approved by the European Medicine Agency (EMA) for the treatment of children and adolescents (at least 3 years of age) with chronic hepatitis C (CHC) genotype 1, 3, and 4 infection. The aim of this study was to evaluate the efficacy and safety of SOF/LDV in adolescents (12 to &lt;18 years old) with CHC in the real-world setting. METHODS: Prospective, open-label, multicentre study involving 12 Italian centres. Patients received the fixed-dose combination of SOF/LDV (400/90 mg) once daily ± ribavirin as per EMA approval and recommendations. The key efficacy endpoint was sustained virological response 12 weeks after the end of treatment (SVR12) as per intention-to-treat analysis. Safety was assessed by adverse events and clinical/laboratory data. RESULTS: Seventy-eight consecutive adolescents (median age 15.2 years, range 12-17.9; girls 53.8%) were enrolled and treated between June 2018 and December 2019. Genotype distribution was as follows: genotype 1 (82.1%), 3 (2.5%), and 4 (15.4%). Seventy-six (97.4%) patients completed treatment and follow-up. Overall, SVR12 was 98.7%. One patient was lost to follow-up after 4 weeks of treatment; 1 patient completed treatment and missed the follow-up visit. No virological breakthrough or relapse were observed. No patient experienced grade 3 to 4 adverse event or serious adverse event. CONCLUSIONS: The results of this real-world study confirmed the high efficacy and the optimal safety profile of SOF/LDV for treatment of CHC in adolescents

Iliac branch devices with standard vs fenestrated/branched stent-grafts: does aneurysm complexity produce worse outcomes? Insights from the pELVIS Registry

Purpose: To compare the outcomes of iliac branch devices (IBD) used in combination with standard endovascular aneurysm repair (EVAR) vs with fenestrated/branched EVAR (f/bEVAR) to treat complex aortoiliac aneurysms. Materials and Methods: The pELVIS Registry database containing the outcomes of IBD use at 8 European centers was interrogated to identify all IBD procedures that were combined with either standard EVAR or f/bEVAR. Among 669 patients extracted from the database, 629 (mean age 72.1±8.8 years; 597 men) had received an IBD combined with standard EVAR vs 40 (mean age 71.1±8.0 years; 40 men) who underwent f/bEVAR with an IBD. The mean aortic aneurysm diameters were 46.4±13.3 mm in the f/bEVAR patients vs 45.0±15.5 mm in the standard EVAR cases. The groups were similar in terms of baseline clinical characteristics and aneurysm morphology. The Kaplan-Meier method was used to compare patient survival, IBD occlusion, type III endoleak, and aneurysm-related reinterventions in follow-up. The estimates are presented with the 95% confidence interval (CI). Results: Technical success was 100% in the f/bEVAR+IBD group and 99% in the EVAR+IBD group (p=0.85). The 30-day mortality was 0% vs 0.5%, respectively (p=0.66), while the 30-day reintervention rates were 7.5% vs 4.1% (p=0.31). The mean follow-up was 32.1±21.3 months for f/bEVAR+IBD patients (n=30) and 35.5±26.8 months for EVAR+IBD patients (n=571; p=0.41). The 12-month survival estimates were 93.4% (95% CI 93.2% to 93.6%) in the EVAR+IBD group vs 93.6% (95% CI 93.3% to 93.9%) for the f/bEVAR+IBD group (p=0.93). There were no occlusions or type III endoleaks in the f/bEVAR+IBD group at 12 months, while the estimates for freedom from occlusion and from type III endoleak in the EVAR+IBD group were 97% (95% CI 96.8% to 97.2%) and 98.5% (95% CI 98.4% to 98.6%), respectively. The 12-month estimates for freedom for aneurysm-related reintervention were 93% (95% CI 92.7% to 93.3%) in the EVAR+IBD group vs 86.4% (95% CI 85.9% to 86.9%) in the f/bEVAR+IBD patients (p=0.046). Conclusion: Treatment of complex aortoiliac disease with f/bEVAR+IBD can achieve equally good early and 1-year outcomes compared to treatment with IBDs and standard bifurcated stent-grafts, except for a somewhat higher reintervention rate in f/bEVAR patients