Differences in the incidence and clinical outcomes of SARS-CoV-2 infection between Italian and non-Italian nationals using routine data.

OBJECTIVES: This study was to compare the incidence and clinical outcomes of SARS-CoV-2 infection between Italian and non-Italian nationals. STUDY DESIGN: We retrospectively analysed data from the COVID-19 Italian integrated surveillance system (14 September 2020 to 17 October 2021). METHODS: We used multivariable Cox proportional hazards models to estimate the hazard ratio (HR) of infection and, among cases, the HRs of death, hospitalisation and subsequent admission to intensive care unit in non-Italian nationals relative to Italian nationals. Estimates were adjusted for differences in sociodemographic characteristics and in the week and region of diagnosis. RESULTS: Of 4,111,067 notified cases, 336,265 (8.2%) were non-Italian nationals. Compared with Italian nationals, non-Italians showed a lower incidence of SARS-CoV-2 infection (HR = 0.81, 95% confidence interval [CI]: 0.80-0.81). However, once diagnosed, they were more likely to be hospitalised (HR = 1.90, 95% CI: 1.87-1.92) and then admitted to intensive care unit (HR = 1.08, 95% CI: 1.04-1.13), with differences larger in those coming from countries with a lower human development index. Compared with Italian cases, an increased rate of death was observed in non-Italian cases from low-human development index countries (HR = 1.41, 95% CI: 1.23-1.62). The HRs of SARS-CoV-2 infection and severe outcomes slightly increased after the start of the vaccination campaign. CONCLUSIONS: Underdiagnosis and delayed diagnosis in non-Italian nationals could explain their lower incidence compared with Italians and, among cases, their higher probability to present clinical conditions leading to worse outcomes. Facilitating early access to vaccination, diagnosis and treatment would improve the control of SARS-CoV-2 transmission and health outcomes in this vulnerable group.

Diagnostic role of internal mammary lymph node involvement in tuberculous pleurisy: a multicenter study.

BACKGROUND AND OBJECTIVES: Diagnosis of tuberculous pleurisy (TP) may be challenging and it often requires pleural biopsy. A tool able to increase pre-test probability of TP may be helpful to guide diagnostic work-up and enlargement of internal mammary lymph node (IMLN) has been suggested to play a potential role. The aim of the present investigation was to assess role of IMLN involvement in TP in a multi-centric case-control study, by comparing its prevalence and test performance to those observed in patients with infectious, non-tuberculous pleurisy (NTIP), and in controls free from respiratory diseases (CP). METHODS: A total of 419 patients, from 14 Pulmonology Units across Italy were enrolled (127 patients affected by TP, 163 affected by NTIP and 129 CP). Prevalence, accuracy and predictive values of ipsilateral IMLN involvement between cases and control groups were assessed, as well as concordance between chest computed tomography (CT scan) and thoracic ultrasound (TUS) measurements. RESULTS: The prevalence of ipsilateral IMLN involvement in TP was significantly higher than that observed in NTIP and CP groups (respectively 77.2%, 39.3% and 14.7%). Results on test performance, stratified by age, revealed a high positive predictive value in patients aged ≤50 years, while a high negative predictive value in patients aged >50 years. The comparison between CT scan and ultrasound showed moderate agreement (Kappa=0.502). CONCLUSIONS: Evaluation of IMLN involvement plays a relevant role in assessing the pre-test probability of TP. Considering the increasing global prevalence of mycobacterial infections, a tool able to guide diagnostic work-up of suspected TP is crucial, especially where local sources are limited.

Dyslipidaemia after switch to tenofovir alafenamide (TAF)-based cART regimens in a cohort of HIV-positive patients: what clinical relevance?

OBJECTIVES: Switching from tenofovir (TDF) to tenofovir alafenamide (TAF) affects lipid profile. The aim of this study was to evaluate whether this results in an increased frequency of patients with low-density lipoprotein (LDL) above their cardiovascular-related target. METHODS: All HIV patients switching from TDF to TAF, with no changes of the anchor drug, and with plasma lipids available within 6 months before and after the switch, were included. Demographic, HIV-related parameters, cardiovascular (CV) risk factors and lipid profile on both TDF and TAF were collected. The CV risk score and the relative target of LDL for each patient were calculated according to 2016 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for the management of dyslipidaemias. Modifications in lipid profiles and in the prevalence of patients with LDL above their CV-related target were evaluated after switch to TAF. RESULTS: Overall, 221 HIV patients were included, according to CV risk: 55% at low risk, 34% at moderate risk, and 11% at high/very high risk. By analysing lipid profiles according to CV risk, 38% of patients on TDF had LDL above their CV target; this prevalence increases to 60% after switching to TAF (P < 0.0001). The presence of cobicistat in the combination antiretroviral therapy (cART) regimen was associated with an increased risk of LDL above the CV-related target after switch to TAF [adjusted odds ratio (aOR) = 2.4, 95% confidence interval (CI): 1-5.1], P = 0.03) and with an increased prescription of lifestyle/therapeutic intervention (OR = 3.0, 95% CI: 1.7-5.3, P < 0.0001). DISCUSSION: Switching from TDF to TAF affects lipid parameters, and data from real life suggest a clinical relevance of this worsening that often leads clinicians to implement lifestyle/therapeutic interventions.

Predictors of incomplete viral response and virologic failure in patients with acute and early HIV infection. Results of Italian Network of ACuTe HIV InfectiON (INACTION) cohort.

OBJECTIVES: The aim of this study was to evaluate the factors that can influence an incomplete viral response (IVR) after acute and early HIV infection (AEHI). METHODS: This was a retrospective, observational study including patients with AEHI (Fiebig stages I-V) diagnosed between January 2008 and December 2014 at 20 Italian centres. IVR was defined by: (1) viral blip (51-1000 HIV-1 RNA copies/mL after achievement of < 50 HIV-1 RNA copies/mL); (2) virologic failure [> 1000 copies/mL after achievement of < 200 copies/mL, or ≥ 200 copies/mL after 24 weeks on an antiretroviral therapy (ART)]; (3) suboptimal viral response (> 50 copies/mL after 48 weeks on ART or two consecutive HIV-1 RNA levels with ascending trend during ART). Cox regression analysis was used to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for IVR. RESULTS: In all, 263 patients were studied, 227 (86%) males, with a median [interquartile range (IQR)] age of 38 (30-46) years. During a median follow-up of 13.0 (5.7-31.1) months, 38 (14.4%) had IVR. The presence of central nervous system (CNS) symptoms was linked to a higher risk of IVR (HR = 4.70, 95% CI: 1.56-14.17), while a higher CD4/CD8 cell count ratio (HR = 0.13, 95% CI: 0.03-0.51 for each point increase) and first-line ART with three-drug regimens recommended by current guidelines (HR = 0.40, 95% CI: 0.18-0.91 compared with other regimens including four or five drugs, older drugs or non-standard backbones) were protective against IVR. CONCLUSIONS: Patients with lower CD4/CD8 ratio and CNS symptoms could be at a higher risk of IVR after AEHI. The use of recommended ART may be relevant for improving short-term viral efficacy in this group of patients.

Plasma levels of protein C pathway proteins and brain magnetic resonance imaging volumes in multiple sclerosis.

BACKGROUND AND PURPOSE: The involvement of protein C (PC) pathway components in multiple sclerosis (MS) has scarcely been explored. The aim was to investigate their levels in relation to clinical and neurodegenerative magnetic resonance imaging (MRI) outcomes in patients. METHODS: In all, 138 MS patients and 42 healthy individuals were studied. PC, protein S (PS) and soluble endothelial protein C receptor (sEPCR) were evaluated by multiplex assays and enzyme-linked immunosorbent assay. Regression analyses between 3 T MRI outcomes and PC pathway components were performed. ancova was used to compare MRI volumes based on protein level quartiles. Partial correlation was assessed amongst levels of PC pathway components and hemostasis protein levels, including soluble thrombomodulin (sTM), heparin cofactor II (HCII), plasminogen activator inhibitor 1 (PAI-1) and factor XII (FXII). The variation of PC concentration across four time points was evaluated in 32 additional MS patients. RESULTS: There was an association between PC concentration, mainly reflecting the zymogen PC, and MRI measures for volumes of total gray matter (GM) (P = 0.003), thalamus (P = 0.007), cortex (P = 0.008), deep GM (P = 0.009) and whole brain (P = 0.026). Patients in the highest PC level quartile were characterized by the lowest GM volumes. Correlations of PC-HCII, PC-FXII and sEPCR-sTM values were detectable in MS patients, whilst PC-PS and PS-PAI-1 correlations were present in healthy individuals only. CONCLUSIONS: Protein C plasma concentrations might be associated with neurodegenerative MRI outcomes in MS. Several differences in correlation amongst protein plasma levels suggest dysregulation of PC pathway components in MS patients. The stability of PC concentration over time supports a PC investigation in relation to GM atrophy in MS.

A 200 km-long mercury contamination of the Paglia and Tiber floodplain: Monitoring results and implications for environmental management.

This paper reports the results of a joint project carried out by three regional environmental agencies of Italy to evaluate long-range mercury (Hg) transport from the abandoned Mt. Amiata Hg district in southern Tuscany (the third largest worldwide site for Hg production) to the fluvial ecosystems of the Paglia and Tiber rivers. Most of the work focused on stream sediments, surface waters and soils. A preliminary survey of Hg0 content in air was also conducted. Data obtained by public health authorities on Hg in vegetables and fish were also included. The highest Hg concentrations (up to thousands of µg/g Hg) were observed in stream sediments and soils directly impacted by Hg mine runoff. Although progressive Hg dilution was observed from north to south along the river, sediments and soils show anomalous Hg levels for over 200 km downstream of Mt. Amiata, testifying to an extreme case of long-range Hg contamination. A pervasive redistribution of Hg is observed in all sediment compartments. Presumably, the width of the impacted fluvial corridor corresponds to the entire alluvial plains of the rivers. The floodplains can be considered new sources for downstream Hg redistribution, especially during large flood events. On the other hand, results from water, air, and vegetable sampling indicate low potential for human exposure to Hg. The extent and distribution of the contamination make remediation not viable. Therefore, people and human activities must coexist with such an anomaly. On the technical side, the most urgent action to be taken is a better definition of the exact extent of the contaminated area. On the management side, it is necessary to identify which public institution(s) can best deal with such a widespread phenomenon. According to the precautionary principle, the impact of the contamination on human activities in the affected areas should be considered.

Hemostasis biomarkers in multiple sclerosis.

BACKGROUND AND PURPOSE: The aim was to investigate the plasma levels of hemostasis components in multiple sclerosis (MS) and their association with clinical and magnetic resonance imaging (MRI) outcomes. METHODS: In all, 138 MS patients [85 with relapsing-remitting MS (RR-MS) and 53 with progressive MS (P-MS) with a mean age of 54 years; 72.5% female; median Expanded Disability Status Scale 3.5; mean disease duration 21 years] and 42 age- and sex-matched healthy individuals (HI) were studied. All subjects were examined with 3 T MRI and clinical examinations. Plasma levels of hemostasis factors [procoagulant, factor XII (FXII)] and inhibitors [tissue factor pathway inhibitor (TFPI), thrombomodulin, heparin cofactor II, a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) and plasminogen activator inhibitor 1 (PAI-1)] were evaluated by magnetic Luminex assays and enzyme-linked immunosorbent assay. Associations between hemostasis plasma levels and clinical and MRI outcomes were assessed. RESULTS: Lower ADAMTS13 levels were found in MS patients compared to HI (P = 0.008) and in MS patients presenting with cerebral microbleeds compared to those without (P = 0.034). Higher PAI-1 levels were found in MS patients compared to HI (P = 0.02). TFPI levels were higher in the P-MS subgroup compared to RR-MS patients (P = 0.011) and compared to HI (P = 0.002). No significant associations between hemostasis plasma levels and clinical or MRI outcomes were found. CONCLUSIONS: Decreased ADAMTS13, particularly in MS patients with cerebral microbleeds, which deserves further investigation, and increased PAI-1 and TFPI levels were observed in MS patients, which deserves further investigation. No relationship between hemostasis plasma levels and measures of disease severity was detected.

Unconventional T cells in chronic hepatitis B patients on long-term suppressive therapy with tenofovir followed by a Peg-IFN add-on strategy: A randomized study.

HBV eradication in chronic hepatitis B (CHB) subjects is rarely achieved with either nucleos(t)ide analogues (NA) or pegylated interferon (Peg-IFN), which both have a limited effect in restoring immune responses. Thirty CHB subjects on long-term treatment with tenofovir (TDF) and HBV suppression were enrolled and randomized 1:2 to either receive Peg-IFN-α-2a add-on therapy or continue TDF alone. We studied γδ T and iNKT frequency and function (by flow cytometry) at baseline, at 12 weeks and 12 weeks after the end of treatment. A higher reduction in qHBsAg occurred in the add-on group compared with the NA group at W12 (P = .016) and at W24 (P = .012). A decline of qHBsAg ≥0.5 log10 at week 24 occurred in 4 of 10 patients in the add-on arm and 1 of 20 in the NA arm, respectively (P = .03). HBsAg loss was seen in 20% of subjects in the add-on group and in none of the NA group. Compared to HBV negative, CHB on TDF showed lower frequency of iNKT (P = .03) and γδ T cells (P = .03) as well as fewer γδ T cells expressing Vδ2 T-cell receptors (P = .005). No changes in unconventional T-cell frequency and function were shown in both add-on and NA patients nor were differences detected between the two treatment groups. We report persistent impairment of unconventional T cells in CHB. Despite a greater qHBsAg decline of add-on patients, our data failed to detect any effect of Peg-IFN treatment on unconventional T cells.

Implementation of GOLD consensus report in real life: results from the Velletri-Lariano (VELA) cohort.

BACKGROUND: COPD is one of the leading causes of morbidity and mortality. Pharmacotherapy improves quality of life and reduces exacerbations although low adherence with prescribed treatments may represent a barrier to optimal disease management. The first objective of this paper is to report the distribution of COPD patients according to GOLD categories, in a sample of patients from a cohort study in an area of the Latium region in Italy. The second objective is to evaluate the agreement between the distributions of severity obtained from the HCPs and the experts included in the study board (Board). METHODS: COPD patients were given a card to collect demographic and clinical data at baseline. Information in those cards was independently evaluated by HCPs and Board to include each patient into one of the four GOLD categories. RESULTS: In a sample of 187 stable COPD patients, 59% male, mean age 70 year, the distribution of GOLD categories according to the Board was: 6% A, 34% B, 2% C, and 58% D. A discrepancy in GOLD classification was observed between the study board and field-based HCPs, regarding more than 50% of the patients, with a clear trend to underestimate the frequency of patients in D level (21%) and to overestimate the frequency in C level (21%). CONCLUSIONS: These results describe for the first time the distribution of COPD patients in an Italian cohort according to the GOLD categories, with the highest frequencies in levels B and D. The misclassification from HCPs may impact the therapeutic approach and the clinical outcomes.

Prevalence of pain in the departments of surgery and oncohematology of a paediatric hospital that has joined the project "Towards pain free hospital".

BACKGROUND: Among hospitalized adults and children pain is undertreated. This study wants to assess the effectiveness of pain therapy in two departments of a large children's hospital. MATERIALS AND METHODS: During a single day work three committees, administering a questionnaire to patients or parents, have evaluated the adherence to international recommendations (JCI and WHO) in the management of analgesic therapy. Patient demographics, prevalence and intensity (moderate and/or severe) of pain (during hospitalization, 24 hours before and at the time of the interview), analgesia (type, route, duration and frequency of administration) and Pain Management Index (=analgesic score-pain score) were recorded. RESULTS: 75 patients participated in the study (age: 2 months up to 24 years, mean 7.8 ± 6). During hospitalization 43 children (57%) had no pain while 32 (43%) have experienced pain. 22 children (29 %) had pain 24 hours before and 12 (16%) at the time of the interview. The average value of the PMI was -0.8±1.3 with a minimum of -3 and a maximum of +2: 60% (19) of the children had a PMI less than 0 (undertreated pain) while 40% (13) had a value=or>0. Out of 32 patients who needed an analgesic therapy 14 (44%) received an around-the-clock dosing, 8 (25%) an intermittent therapy and 10 (31%) no treatment.17 (77 %) were the single drug therapy and 5 (23%) the multimodal ones. CONCLUSIONS: The prevalence of pain in the two departments is high. The main cause is that knowledge is not still well translated into clinical practice.

Assessment of radiological vertebral fractures in HIV-infected patients: clinical implications and predictive factors.

OBJECTIVES: The aim of this study was to evaluate the clinical impact of including lateral spine X-ray in the screening of bone diseases in HIV-positive patients. METHODS: A total of 194 HIV-positive patients underwent dual-energy X-ray absorptiometry (DEXA), lateral spine X-ray and bone biochemical analysis. Vertebral fractures were identified using a morphometric analysis of X-rays and classified using the semiquantitative scoring system of Genant et al. For each patient, a spine deformity index (SDI) score was calculated by summing the grades of vertebral deformities. Reductions in vertebral body height of > 25% were considered vertebral fractures, and those < 25% were considered vertebral deformities. Risk factors associated with vertebral fractures were evaluated by univariate and multivariate analysis. RESULTS: Vertebral fractures were detected in 24 patients (12.4%) and vertebral deformities in 17 patients (8.7%); 153 patients (78.9%) did not show any vertebral deformity. Among patients with fractures, only two with SDI > 10 reported lumbar pain; the remaining were asymptomatic. Patients over 50 years old showed a higher prevalence of vertebral fracture [24.4% versus 11.8% in patients 41-50 years old (P = 0.05) and 1.9% in patients ≤ 40 years old (P = 0.04)]. No significant increase in the prevalence according to bone mineral density (BMD) reduction was observed, and 70% of fractures were diagnosed in nonosteoporotic patients. Older age [adjusted odds ratio 1.09; 95% confidence interval (CI) 1.03-1.13; P = 0.001] and steroid use (adjusted odds ratio 3.64; 95% CI 1.29-10.3; P = 0.01) were independently associated with vertebral fracture; no association was found with HIV- or highly active antiretroviral therapy (HAART)-related variables. CONCLUSIONS: A prevalence of vertebral fractures of 12.4% was observed in our HIV-positive cohort. Given that two-thirds of fractures occurred in nonosteoporotic patients, spine X-ray may be considered in patients at increased risk, irrespective of BMD; that is, in elderly patients and/or patients using steroids.

A screening sampling plan to detect Mycobacterium avium subspecies paratuberculosis-positive dairy herds.

Mycobacterium avium ssp. paratuberculosis (MAP) is the etiological agent of paratuberculosis, a chronic contagious bacterial disease primarily affecting dairy cattle. Paratuberculosis represents a dual problem for the milk production chain: in addition to economic losses to affected herds, MAP may have zoonotic potential. Infected herds must be identified in order to implement programs designed to reduce the incidence of disease within and between herds and to prevent MAP from entering the food chain. The objective of this study was to evaluate the sensitivity and specificity of a screening sampling plan (SSP) to detect MAP-positive dairy herds by repetitive analysis of bulk tank milk (BTM) samples by ELISA and in-line milk filter (ILMF) samples by PCR. Samples from BTM and ILMF were collected twice from 569 dairy herds in southern Italy. Additionally, 12,016 individual milk samples were collected: 9,509 from 102 SSP-positive herds (SSP MAP-positive) and 2,507 from 21 randomly selected SSP-negative herds (SSP MAP-negative). There was a total of 126 SSP MAP-positive herds (i.e., 21.3% SSP MAP-positive herds; 95% confidence interval=18.0-24.9); the within-herd apparent prevalence (AP) ranged between 0.00 and 22.73% (mean 6.07%). A significant difference in within-herd AP was shown between SSP MAP-positive herds and SSP MAP-negative herds. A highly significant association was shown between the median AP herd status (>5%) and positivity to at least one ILMF or BTM sample. The SSP detected a minimum of 56.25% of low AP herds (AP ≤ 2.0%) up to a maximum of 100% of herds with a within-herd AP ≥ 8.0%. Overall, the SSP detected 85.57% of herds in which at least one individual milk sample was positive by ELISA. The proposed SSP was an inexpensive and useful tool to detect MAP-positive herds with a higher risk of infection diffusion and milk contamination. Although the SSP cannot be used for MAP-free certification of herds, it could be useful to prioritize appropriate control measures aimed at reducing the prevalence of infection in dairy herds and milk contamination.

Stillbirth and fetal growth restriction.

OBJECTIVE: To confirm the role of fetal growth restriction (FGR) as a cause of stillbirth, and to compare diagnostic accuracy of customized fetal growth and population-based standards in identifying FGR within a pathological population of early and late stillbirths. METHODS: Retrospective study on a cohort of 189 stillbirths occurred in single pregnancy between January 2006 and September 2011. Unexplained stillbirths, defined by Aberdeen-Wigglesworth and ReCoDe classifications, were evaluated on the basis of fetal birthweight with both Tuscany population and Gardosi customized standards. Unexplained stillbirths have been classified as early or late depending on the gestational age of occurrence. RESULTS: Aberdeen-Wigglesworth classification, applied to the 189 cases of stillbirth, left 94 unexplained cases (49.7%), whereas the ReCoDe classification left only 40 (21%). By applying population standards to the 94 unexplained stillbirths we have identified 31 FGRs (33% of sample), while customized standards identified 54 FGRs (57%). Customised standards identified a larger number of FGRs with respect to population standards during the third trimester (i.e. 51% vs. 25% respectively) than in the second trimester (73% vs. 54% respectively) (p = 0.05). CONCLUSIONS: Customized standards have a higher diagnostic accuracy in identifying FGRs especially during the third trimester.

Plasma renin concentration as a predictor of outcome in a medical intensive care setting: a retrospective pilot study.

BACKGROUND: Renin and aldosterone are involved in an organ perfusion pathway that may be an estimate of disease severity. The primary objective was to explore the relationship between outcome and aldosterone and renin levels at medical intensive care unit (MICU) admissions in comparison to SAPS II scores. METHODS: This retrospective study was conducted on patients admitted to the adult MICU during 12 months. Exclusion: subjects with creatinine >176 mmol/l, chronic arrhythmia and ACE-inhibitor therapy. Admission aldosterone and renin plasma levels were measured and SAPS II scores were calculated. RESULTS: Eighty-two patients were included. Only the plasma renin median concentration difference between survivors and non-survivors was significant (P=0.0168). The area under the ROC curve for mortality and plasma renin concentration was similar to that of SAPS II. The correlation between mortality and renin >84 pg/mL showed an odds ratio of 5.78±3.45, P=0.003. CONCLUSION: Renin was correlated to outcome in critically ill medical patients.

Quantitative risk assessment of verocytotoxin-producing Escherichia coli O157 and Campylobacter jejuni related to consumption of raw milk in a province in Northern Italy.

A quantitative risk assessment was developed to describe the risk of campylobacteriosis and hemolytic uremic syndrome (HUS) linked to consumption of raw milk sold in vending machines in Northern Italy. Exposure assessment considered the microbiological status of dairy farms, expected milk contamination, storage conditions from bulk tank to home storage, microbial growth during storage, destruction experiments, consumption frequency of raw milk, age of consumers, serving size, and consumption preference. The differential risk between milk handled under regulation conditions (4°C throughout all phases) and the worst field handling conditions was considered. The probability of Campylobacter jejuni infection was modeled with a single-hit dose-response beta-Poisson model, whereas for HUS an exponential dose-response model was chosen and two probabilities were used to model the higher susceptibility of children younger than 5 years old. For every 10,000 to 20,000 consumers each year, the models predicted for the best and worst storage conditions, respectively, 2.12 and 1.14 campylobacteriosis cases and 0.02 and 0.09 HUS cases in the 0- to 5-year age group and 0.1 and 0.5 HUS cases in the >5-year age group. The expected pediatric HUS cases do not differ considerably from those reported in Italy by the Minister of Health. The model developed may be a useful tool for extending the assessment of the risk of campylobacteriosis and HUS due to raw milk consumption at the national level in Italy. Considering the epidemiological implications of this study, the risk of illness linked to raw milk consumption should not be ignored and could be reduced by the use of simple measures. Boiling milk before consumption and strict control of temperatures by farmers during raw milk distribution have significant effects on campylobacteriosis and HUS and are essential measures for risk management.