Despite the effectiveness of cART, people living with HIV still experience an increased risk of serious non-AIDS events, as compared to the HIV negative population. Whether pre-cART microbial ...translocation (MT) and systemic inflammation might predict morbidity/mortality during suppressive cART, independently of other known risk factors, is still unclear. Thus, we aimed to investigate the role of pre-cART inflammation and MT as predictors of clinical progression in HIV+ patients enrolled in the Icona Foundation Study Cohort.
We included Icona patients with ≥2 vials of plasma stored within 6 months before cART initiation and at least one CD4 count after therapy available. Circulating biomarker: LPS, sCD14, EndoCab, hs-CRP. Kaplan-Meier curves and Cox regression models were used. We defined the endpoint of clinical progression as the occurrence of a new AIDS-defining condition, severe non-AIDS condition (SNAEs) or death whichever occurred first. Follow-up accrued from the data of starting cART and was censored at the time of last available clinical visit. Biomarkers were evaluated as both binary (above/below median) and continuous variables (logescale).
We studied 486 patients with 125 clinical events: 39 (31%) AIDS, 66 (53%) SNAEs and 20 (16%) deaths. Among the analyzed MT and pro-inflammatory markers, hs-CRP seemed to be the only biomarker retaining some association with the endpoint of clinical progression (i.e. AIDS/SNAEs/death) after adjustment for confounders, both when the study population was stratified according to the median of the distribution (1.51 mg/L) and when the study population was stratified according to the 33% percentiles of the distribution (low 0.0-1.1 mg/L; intermediate 1.2-5.3 mg/L; high > 5.3 mg/L). In particular, the higher the hs-CRP values, the higher the risk of clinical progression (p = 0.056 for median-based model; p = 0.002 for 33% percentile-based model).
Our data carries evidence for an association between the risk of disease progression after cART initiation and circulating pre-cART hs-CRP levels but not with levels of MT. These results suggest that pre-therapy HIV-driven pro-inflammatory milieu might overweight MT and its downstream immune-activation.
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Additionally, COVID-19 reminded us that M&Rs tend to also have suboptimal vaccination coverage compared to the general population due to several concurrent factors 3,4: exclusion from health and ...vaccination plans and systems, often due to a lack of legal entitlements to health care or due to administrative/residence barriers; health system barriers due to language, lack of cultural sensitivity, lack of outreach and community engagement capacity, lack of collaboration with civil society organisations, barriers to primary care, and vaccination services access, including vaccination costs; high mobility of M lack of confidence in the health system and misconceptions about the vaccine. ...including migrants in vaccination programmes not only protects this group, but also decreases the risk of further outbreaks in the community. Generally, M&R’s trust in the system needs to be built since arrival through systemic interventions, such as: firewalls to shield migrants in irregular situations from the possible transfer of their personal data to immigration authorities when they attempt to access health-care services with outreach campaigns to inform migrants in irregular situations 11; access to primary care systems, especially registration with general practicioners, also beyond vaccination; use of trusted groups or sources (non-governmental organizations, community groups) for communication; increased funding for and collaboration with these trusted groups; avoidance of labelling specific groups as “infectious” or “hesitant” to avoid increasing stigmatisation and distrust 12. MONITORING PROGRESS OF INCLUSIVE VACCINATIONS, BASED ON A HEALTH EQUITY PERSPECTIVE Progress in the inclusion of socially vulnerable groups in vaccination, with specific reference to M&Rs, needs to be monitored at national and regional levels through: setting up strategic goals, targets, and indicators for national vaccination plans to allow for monitoring of progress and impact based on health equity and public health perspective (Photo); setting up or expanding immunisation information systems with appropriate disaggregation by key social determinants of health, according to a set of core variables in relation to the migration status 19; setting an appropriate vaccination coverage target related to M&Rs, at least for diseases targeted for elimination or eradication (e.g., polio and measles) to be used as a proxy for inclusiveness.
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We investigated the potential relationship between T-cell phenotype, inflammation, endotoxemia, and atherosclerosis evaluated by carotid intima-media thickness (IMT) in a cohort of HIV-positive ...patients undergoing long-term virologically suppressive combination antiretroviral therapy (cART).
We studied 163 patients receiving virologically suppressive cART.
We measured IMT (carotid ultrasound); CD4+/CD8+ T-cell activation (CD38, CD45R0), differentiation (CD127), apoptosis (CD95), and senescence (CD28, CD57) (flow cytometry); plasma sCD14, IL-6, TNF- α, sVCAM-1, hs-CRP, anti-CMV IgG (ELISA); LPS (LAL). The results were compared by Mann-Whitney, Kruskal-Wallis or Chi-square tests, and factors associated with IMT were evaluated by multivariable logistic regression.
Of 163 patients, 112 demonstrated normal IMT (nIMT), whereas 51 (31.3%) had pathological IMT (pIMT: ≥1 mm). Of the patients with pIMT, 22 demonstrated an increased IMT (iIMT), and 29 were shown to have plaques. These patient groups had comparable nadir and current CD4+, VLs and total length of time on cART. Despite similar proportions of CD38-expressing CD8+ cells (p = .95), pIMT patients exhibited higher activated memory CD8+CD38+CD45R0+ cells (p = .038) and apoptotic CD4+CD95+ (p = .01) and CD8+CD95+ cells (p = .003). In comparison to nIMT patients, iIMT patients tended to have lower numbers of early differentiated CD28+CD57- memory CD4+ (p = .048) and CD28-CD57-CD8+ cells (p = .006), both of which are associated with a higher proliferative potential. Despite no differences in plasma LPS levels, pIMT patients showed significantly higher circulating levels of sCD14 than did nIMT patients (p = .046). No differences in anti-CMV IgG was shown. Although circulating levels of sCD14 seemed to be associated with a risk of ATS in an unadjusted analysis, this effect was lost after adjusting for classical cardiovascular predictors.
Despite the provision of full viral suppression by cART, a hyperactivated, pro-apoptotic T-cell profile characterizes HIV-infected patients with early vascular damage, for whom the potential contribution of subclinical endotoxemia and anti-CMV immunity should be investigated further.
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Individuals lacking immune recovery during suppressive cART will still represent a clinical issue in the years to come, given the high proportion of HIV-infected subjects introducing therapy late in ...the course of disease. Understanding the mechanisms underlying poor CD4+ T-cell gain is crucial for the correct clinical management of individuals in this context.
An HIV-infected subject with poor CD4+ T-cell gain in the course of suppressive antiretroviral therapy was extensively investigated to identify the mechanisms behind inadequate CD4+ reconstitution. In particular, we studied the phenotype of circulating T-cells, interleukin-7 signaling in peripheral blood and bone marrow, gut function and microbial translocation markers as well as the composition of the faecal microbiota. Numerous therapeutic interventions ranging from antiretroviral therapy intensification to immunotherapy and anti-hepatitis C virus treatment were also employed in order to target the possible causes of poor immune-recovery.
Poor CD4+ T-cell gain on suppressive antiretroviral therapy is multifactorial and thus represents a clinical challenge. Clinicians should investigate subjects' immune profile as well as possible causes of chronic antigenic stimulation for the administration of the most appropriate therapeutic strategies in this setting.
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Both HIV and HCV infections feature increased microbial translocation (MT) and gut dysbiosis that affect immune homeostasis and disease outcome. Given their commitment to antimicrobial mucosal ...immunity, we investigated mucosal-associated invariant T (MAIT) cells and Vα7.2+CD161- T-cell frequency/function and their possible associations with MT and gut dysbiosis, in chronic HIV and/or HCV infections. We enrolled 56 virally infected (VI) patients (pts): 13 HIV+ on suppressive cART (HIV-RNA < 40cp/ml), 13 HCV+ naive to DAA (direct-acting antiviral) anti-HCV agents; 30 HCV+/HIV+ on suppressive cART and naive to anti-HCV. 13 age-matched healthy controls (HC) were enrolled. For Vα7.2+CD161++ and Vα7.2+CD161-CD8+ T cells we assessed: activation (CD69), exhaustion (PD1/CD39), and cytolytic activity (granzymeB/perforin). Following PMA/ionomycin and
stimulation we measured intracellular IL17/TNFα/IFNγ. Markers of microbial translocation (Plasma LPS, 16S rDNA, EndoCAb and I-FABP) were quantified. In 5 patients per group we assessed stool microbiota composition by 16S targeted metagenomics sequencing (alpha/beta diversity, relative abundance). Compared to controls, virally infected pts displayed significantly lower circulating Vα7.2+CD161++CD8+ MAIT cells (
= 0.001), yet expressed higher perforin (
= 0.004) and granzyme B (
= 0.002) on CD8+ MAIT cells. Upon
stimulation, the residual MAIT cells are less functional particularly those from HIV+/HCV+ patients. Conversely, in virally infected pts, Vα7.2+CD161-CD8+ cells were comparable in frequency, highly activated/exhausted (CD69+:
= 0.002; PD-1+:
= 0.030) and with cytolytic potential (perforin+:
< 0.0001), yet were poorly responsive to
stimulation. A profound gut dysbiosis characterized virally infected pts, especially HCV+/HIV+ co-infected patients, delineating a
-poor/
rich microbiota, with significant associations with MAIT cell frequency/function. Irrespective of mono/dual infection, HIV+ and HCV+ patients display depleted, yet activated/cytolytic MAIT cells with reduced
function, suggesting an impoverished pool, possibly due to continuous bacterial challenge. The MAIT cell ability to respond to bacterial stimulation correlates with the presence of
and
, possibly suggesting an association between gut dysbiosis and MAIT cell function and posing viral-mediated dysbiosis as a potential key player in the hampered anti-bacterial MAIT ability.
Objectives:
Access to vaccination for newly arrived migrants (NAMs) is a relevant concern that requires urgent attention in EU/EEA countries. This study aimed to develop a General Conceptual ...Framework (GCF) for understanding how to improve vaccination coverage for NAMs, by characterizing and critically analyzing system barriers and possible strategies to increase vaccination.
Methods:
A theoretical conceptualization of the GCF was hypothesized based on conceptual hubs in the immunization process. Barriers and solutions were identified through a non-systematic desktop literature review and qualitative research. The GCF guided the activities and facilitated the integration of results, thereby enriching the GCF with content.
Results:
The study explores the vaccination of NAMs and proposes strategies to overcome barriers in their vaccination process. It introduces a framework called GCF, which consists of five interconnected steps: entitlement, reachability, adherence, achievement, and evaluation of vaccination. The study also presents barriers and solutions identified through literature review and qualitative research, along with strategies to enhance professionals’ knowledge, improve reachability, promote adherence, achieve vaccination coverage, and evaluate interventions. The study concludes by recommending strategies such as proximity, provider training, a migrant-sensitive approach, and data collection to improve vaccination outcomes for NAMs.
Conclusion:
Ensuring equitable access to healthcare services, including vaccination, is crucial not only from a humanitarian perspective but also for the overall public health of these countries.
Gastric cancer (GC) is the fifth most diagnosed cancer, but it is the third leading cause of cancer death worldwide. Despite the likelihood of gastric cancer metastasizing to the peritoneum, optimal ...management strategies for this population remain undefined. We carried out a retrospective analysis to present our findings on patients with advanced gastric cancer (AGC) with peritoneal metastases (CP) who underwent neoadjuvant chemotherapy followed by gastrectomy + hyperthermic intraperitoneal chemotherapy (HIPEC). To better understand the data, we compared these patients with AGC patients without CP who were treated with neoadjuvant chemotherapy and surgery, as well as with another group of patients who underwent upfront surgery. Patients who undergo surgery and HIPEC achieve a higher survival rate than patients in the literature who undergo only palliative chemotherapy with a median overall survival of 28 months with a low incidence of major complications.
(1) The COVID-19 pandemic exacerbated health disparities, both between foreign and autochthonous populations. Italy was one of the European countries that was the most affected by the COVID-19 ...pandemic; however, only limited data are available on vaccine willingness. This study aims to assess the propensity of foreign and autochthonous populations residing in Italy to be vaccinated and the relative associated factors. (2) Data were collected and analysed from the two Italian surveillance systems, PASSI and PASSI d'Argento, in the period of August 2020-December 2021. The data include those of the Italian resident adult population over 18 years old. A multinomial logistic regression model, stratified by citizenship, was used to assess the associations of sociodemographic, health, and COVID-19 experience variables with vaccination attitudes. (3) This study encompassed 19,681 eligible subjects. Considering the willingness to be vaccinated, foreign residents were significantly less certain to get vaccinated (49.4% vs. 60.7% among Italians). Sociodemographic characteristics, economic difficulties, and trust in local health units emerged as factors that were significantly associated with vaccine acceptance. Having received the seasonal flu vaccine was identified as a predictor of COVID-19 vaccine acceptance among foreign and Italian residents. (4) This study underscores the significance of tailoring interventions to address vaccine hesitancy based on the diverse characteristics of foreign and Italian residents. This research offers practical insights for public health strategies, highlighting the importance of tailored educational campaigns, improved communication, and nuanced interventions to enhance vaccine acceptance and uptake within both populations.
Bendamustine, used for the treatment of indolent B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia, is known to cause prolonged myelosuppression and lymphocytopenia and has been associated ...with the risk of developing serious and fatal infections. While reports of localized CMV infections in asymptomatic patients exist, disseminated CMV disease has not been described.
We report the first case of disseminated CMV infection in a 75-year-old male diagnosed with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia with massive bone marrow infiltration. Despite 6-cycle R-bendamustine chemotherapy resulted in a good partial response, the patient developed persistent fever and severe weight loss. Analysis of cerebrospinal fluid and peripheral blood revealed the presence of CMV-DNA, while the fundus oculi examination revealed bilateral CMV retinitis. Treatment with induction and maintenance drugs was complicated by neutropenia and deterioration of renal function with electrolyte imbalance. From an immunological standpoint, we observed a profound imbalances in phenotype and function of B- and T-cell subsets, with a high proportion of circulating total, activated CD69+ and CD80+ B-cells, a low γ/δ T-cell frequency with a high proportion of CD69- and CD38-expressing cells, and hyperactivated/exhausted CD4+ and CD8+ T-cell phenotypes unable to face CMV challenge.
We hereby describe a severe form of disseminated CMV disease after R-bendamustine treatment. Our observations strongly support the careful clinical monitoring of CMV reactivation/infection in oncologic patients undergoing this therapeutic regimen.
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