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Background. Combination antiretroviral therapy (cART) has progressively decreased mortality of HIV-associated tuberculosis .To date, however, limited data on tuberculosis treatment outcomes among coinfected patients who are not ART-naive at the time of tuberculosis diagnosis are available. Methods. A multicenter, observational study enrolled 246 HIV-infected patients diagnosed with tuberculosis, in 96 Italian infectious diseases hospital units, who started tuberculosis treatment. A polytomous logistic regression model was used to identify baseline factors associated with the outcome. A Poisson regression model was used to explain the effect of ART during tuberculosis treatment on mortality, as a time-varying covariate, adjusting for baseline characteristics. Results. Outcomes of tuberculosis treatment were as follows: 130 (52.8%) were successfully treated, 36 (14.6%) patients died in a median time of 2 months (range: 0-16), and 80 (32.6%) had an unsuccessful outcome. Being foreign born or injecting drug users was associated with unsuccessful outcomes. In multivariable Poisson regression, cART during tuberculosis treatment decreased the risk of death, while this risk increased for those who were not ART-naive at tuberculosis diagnosis. Conclusions. ART during tuberculosis treatment is associated with a substantial reduction of death rate among HIV-infected patients. However, patients who are not ART-naive when they develop tuberculosis remain at elevated risk of death. [ABSTRACT FROM AUTHOR]

Presents information on a study which assessed changes in clinical presentation and outcome of HIV-associated tuberculosis (TB) before and after widespread implementation of highly active antiretroviral therapy. Subjects and methods; Statistical analysis; Mortality of HIV patients with TB.

Background: Drug-induced liver injury (DILI) secondary to ATT treatment (TB-DILI) is reported in 2–28% of patients. We present here a series of clinical cases of suspected DILI arising during antituberculosis treatment, studied with the aid of liver biopsy. Methods: this was a retrospective descriptive study including 10 tuberculosis patients who underwent liver biopsy for suspected TB-DILI at the "Lazzaro Spallanzani" Institute from 2017 to 2022. Results: Ten patients who underwent LB were extracted from the database and included in the retrospective study cohort. According to the clinical classification, eight patients had hepatocellular liver injury, one patient had cholestatic injury, and another had mixed-type injury. Histopathological diagnosis revealed liver damage due to DILI in 5/10 (50%) cases. In one case, liver biopsy showed necrotizing granulomatous hepatitis. Conclusions: Severe and persistent elevation of hepatic transaminases, hepatic cholestasis despite discontinuation of therapy, and other suspected hepatic conditions are indications for liver biopsy, which remains a valuable tool in the evaluation of selected tuberculosis patients with suspected DILI for many reasons. However, the decision to perform a liver biopsy should be based on clinical judgment, considering the benefits and risks of the procedure. [ABSTRACT FROM AUTHOR]

Space charge can affect significantly the reliability of DC cross-linked polyethylene (XLPE) power cables. For limiting the injection and accumulation of space charge, specimens with graphene coating applied on a sandwich composed of XLPE and semiconductive layer were made. Space charge distribution of specimens was measured at 10 and 40 kV/mm. The measuring results show that when graphene is coated on the semiconductive side, negative charge accumulates in XLPE, and the quantity of positive charge injected from anode is significantly reduced. When XLPE is coated with graphene, little space charge is injected into XLPE, and positive charge accumulates near the interface of XLPE and electrode, which lowers electric field near the anode. [ABSTRACT FROM AUTHOR]

Patients who were intubated and on invasive mechanical ventilation at screening were excluded, while patients with known chronic parenchymal lung disease were allowed in the study. Keywords: COVID-19; interstitial lung disease; lung fibrosis; pulmonary fibrosis EN COVID-19 interstitial lung disease lung fibrosis pulmonary fibrosis 954 957 4 09/20/23 20231001 NES 231001 DATA AVAILABILITY STATEMENT The data that support the findings of this study are available from the corresponding author upon reasonable request. Taken together, the findings of this study did not hint at any additional beneficial effect of pamrevlumab in patients with COVID-19 pneumonia as compared to SOC alone, at least not in the short term. Antifibrotic drugs have been so far investigated in chronic fibrotic disorders, and whether they could act fast enough to contrast the rapid evolution of COVID-19 pneumonia is unknown. Chronic respiratory comorbidities were infrequent in the study population, as two patients had diagnosis of chronic obstructive pulmonary disease and one patient had diagnosis of interstitial lung disease. [Extracted from the article]

Tuberculosis (TB) is a prevalent disease causing an estimated 1.6 million deaths and 10.6 million new cases annually. Discriminating TB disease from differential diagnoses can be complex, particularly in the field. Increased levels of complement component C1q in serum have been identified as a specific and accessible biomarker for TB disease but the source of C1q in circulation has not been identified. Here, data and samples previously collected from human cohorts, a clinical trial and a non-human primate study were used to identify cells producing C1q in circulation. Cell subset frequencies were correlated with serum C1q levels and combined with single cell RNA sequencing and flow cytometry analyses. This identified monocytes as C1q producers in circulation, with a pronounced expression of C1q in classical and intermediate monocytes and variable expression in non-classical monocytes. [ABSTRACT FROM AUTHOR]

• A guideline update regarding drug-resistant tuberculosis (DR-TB) treatment has been recently published by World Health Organization. • 6-month bedaquiline, pretomanid, linezolid (600 mg), and moxifloxacin (BPaLM) is recommended rather than 9-month or longer regimens in multi DR/rifampicin-resistant TB (MDR/RR-TB). • 9-month regimen is suggested instead of longer regimens in fluoroquinolones-susceptible MDR/RR-TB. • 18-month regimens remain a valid option if shorter regimens cannot be implemented. • Further studies to clarify the use of bedaquiline, pretomanid, and linezolid/BPaLM in special situations are needed. In December 2022 World Health Organization released a new treatment for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) guideline. The main novelty of this update is two new recommendations (i) a 6-month treatment regimen composed of bedaquiline, pretomanid, linezolid (600 mg), and moxifloxacin (BPaLM) is recommended in place of the 9-month or longer (18-month) regimens in MDR/RR-TB patients, now including extensive pulmonary TB and extrapulmonary TB (except TB involving central nervous system, miliary TB and osteoarticular TB); (ii) the use of the 9-month all-oral regimen rather than longer (18-months) regimen is suggested in patients with MDR/RR-TB and in whom resistance to fluoroquinolones has been excluded. Longer (18-month) treatments remain a valid option in all cases in which shorter regimens cannot be implemented due to intolerance, drug-drug interactions, extensively drug-resistant tuberculosis, extensive forms of extrapulmonary TB, or previous failure. The new guidelines represent a milestone in MDR/RR-TB treatment landscape, setting the basis for a shorter, all-oral, more acceptable, equitable, and patient-centered model for MDR/RR-TB management. However, some challenges remain to be addressed to allow full implementation of the new recommendations. [ABSTRACT FROM AUTHOR]

• Tumor necrosis factor-α significantly discriminates tuberculosis (TB)-COVID-19 from COVID-19. • SARS-CoV-2-specific response is significantly impaired in patients with TB-COVID-19. • Mycobacterium tuberculosis -specific response is significantly reduced in patients with TB-COVID-19. To characterize the plasma immune profile of patients with tuberculosis (TB)-COVID-19 compared with COVID-19, TB, or healthy controls and to evaluate in vitro the specific responses to SARS-CoV-2 and Mycobacterium tuberculosis (Mtb)-antigens. We enrolled 119 subjects: 14 TB-COVID-19, 47 COVID-19, 38 TB, and 20 controls. The plasmatic levels of 27 immune factors were measured at baseline using a multiplex assay. The specific response to SARS-CoV-2 and Mtb antigens was evaluated using a home-made whole blood platform and QuantiFERON-Plus tubes, respectively. We found an immune signature (tumor necrosis factor [TNF]-α, macrophage inflammatory protein-1β, and interleukin [IL]-9) associated with TB-COVID-19 coinfection compared with COVID-19 (P <0.05), and TNF-α showed the highest discriminant power. We also found another signature (TNF-α, IL-1β, IL-17A, IL-5, fibroblast growth factor-basic, and granulocyte macrophage colony-stimulating factor [GM-CSF]) in coinfected patients compared with patients with TB (P <0.05), and among them, TNF-α and granulocyte macrophage colony-stimulating factor showed a non-negligible discriminating ability. Moreover, coinfected patients showed a significantly reduced SARS-CoV-2-specific response compared with COVID-19 for several pro-inflammatory cytokines/chemokines, anti-inflammatory cytokines, and growth factors (P ≤0.05). Furthermore, coinfection negatively affected the Mtb-specific response (P ≤0.05). We found immune signatures associated with TB-COVID-19 coinfection and observed a major impairment of SARS-CoV-2-specific and, to a lesser extent, the Mtb-specific immune responses. These findings further advance our knowledge of the immunopathology of TB-COVID-19 coinfection. [ABSTRACT FROM AUTHOR]

Purpose: This study examined the effects of Fil-Rouge Integrated Psycho-Oncological Support (FRIPOS) in a group of women with breast cancer compared with a group receiving treatment as usual (TAU). Methods: The research design was a randomized, monocentric, prospective study with three time points of data collection: after the preoperative phase (T0), in the initial phase of treatments (T1), and 3 months after the start of treatments (T2). The FRIPOS group (N = 103) and the TAU group (N = 79) completed a sociodemographic questionnaire, the Symptom Checklist-90-R (SCL-90-R) at T0; the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30 and EORTC QLQ-BR23 at T1; and SCL-90-R, EORTC QLQ-C30, and EORTC QLQ-BR23 at T2. Results: A series of independent and paired t tests showed that patients in the FRIPOS group performed better on all scales related to symptomatic manifestations and on some quality of life scales (fatigue, dyspnea, and sleep disturbances) at T2. In addition, a series of ten multiple regressions were performed to predict each SCL subscale at T2 from the SCL score at T0 and the EORTC QLQ-C30 scores at T2. In nine of ten regression models (all except somatization), both FRIPOS group membership and QoL subscale contributed significantly to prediction. Conclusions: This study suggests that patients in the FRIPOS group have more benefits in emotional, psychological, and collateral symptoms than patients in the TAU group and that these improvements are due to integrated psycho-oncology care. [ABSTRACT FROM AUTHOR]

Most patients infected with SARS-CoV-2 display mild symptoms with good prognosis, while 20% of patients suffer from severe viral pneumonia and up to 5% may require intensive care unit (ICU) admission due to severe acute respiratory syndrome, which could be accompanied by multiorgan failure. Plasma proteomics provide valuable and unbiased information about disease progression and therapeutic candidates. Recent proteomic studies have identified molecular changes in plasma of COVID-19 patients that implied significant dysregulation of several aspects of the inflammatory response accompanied by a general metabolic suppression. However, which of these plasma alterations are associated with disease severity remains only partly characterized. A known limitation of proteomic studies of plasma samples is the large difference in the macromolecule abundance, with concentration spanning at least 10 orders of magnitude. To improve the coverage of plasma contents, we performed a deep proteomic analysis of plasma from 10 COVID-19 patients with severe/fatal pneumonia compared to 10 COVID-19 patients with pneumonia who did not require ICU admission (non-ICU). To this aim, plasma samples were first depleted of the most abundant proteins, trypsin digested and peptides subjected to a high pH reversed-phase peptide fractionation before LC–MS analysis. These results highlighted an increase of proteins involved in neutrophil and platelet activity and acute phase response, which is significantly higher in severe/fatal COVID-19 patients when compared to non-ICU ones. Importantly, these changes are associated with a selective induction of complement cascade factors in severe/fatal COVID-19 patients. Data are available via ProteomeXchange with identifier PXD036491. Among these alterations, we confirmed by ELISA that higher levels of the neutrophil granule proteins DEFA3 and LCN2 are present in COVID-19 patients requiring ICU admission when compared to non-ICU and healthy donors. Altogether, our study provided an in-depth view of plasma proteome changes that occur in COVID-19 patients in relation to disease severity, which can be helpful to identify therapeutic strategies to improve the disease outcome. [ABSTRACT FROM AUTHOR]

• The QuantiFERON SARS-CoV-2 research use only assay response is mediated by CD4+ and CD8+ T cells. • Immune response to the antigen (Ag)2 tube is more accurate than that to the Ag1 tube. • Responses to QuantiFERON SARS-CoV-2 tubes are lower compared with a homemade test. • The QuantiFERON SARS-CoV-2 difference in accuracy is likely because of the peptide composition. Objectives: In this study, we aimed to characterize the SARS-CoV-2-specific T cell response detected by the QuantiFERON SARS-CoV-2 research use only assay in terms of accuracy and T cell subsets involved compared with a homemade interferon (IFN)-γ release assay (IGRA). Methods: We evaluated T cell response by the standardized QuantiFERON SARS-CoV-2 tubes (antigen [Ag]1 and Ag2) and a homemade IGRA quantifying IFN-γ response to SARS-CoV-2 spike peptides (homemade-IGRA-SPIKE test). We evaluated the T cell subsets mediating the specific response using flow cytometry. Results: We prospectively enrolled 66 individuals: COVID-19 or post-COVID-19 subjects and NO-COVID-19-vaccinated subjects, including healthy donors and immunocompromised subjects. The standardized kit detected 62.1% (41/66) of T cell responders. Ag2 tube showed a higher IFN-γ quantitative and qualitative response. Ag1 tube response was mainly mediated by CD4+ T cells; Ag2 tube response was mediated by CD4+ and CD8+ T cells. The homemade-IGRA-SPIKE test detected a higher number of responders (52/66, 78.8%) than the QuantiFERON SARS-CoV-2 assay (P = 0.056). The response was found in both T cell subsets, although a higher magnitude and response rate was observed in the CD4+ T cell subset. Conclusion: The QuantiFERON SARS-CoV-2 response is mediated by CD4+ and CD8+ T cells. A lower number of responders is found compared with the homemade-IGRA-SPIKE test, likely because of the different peptide composition. [ABSTRACT FROM AUTHOR]

(1) Background: Although COVID-19 is largely a respiratory disease, it is actually a systemic disease that has a wide range of effects that are not yet fully known. The aim of this study was to determine the incidence, predictors and outcome of non-hepatic hyperammonemia (NHH) in COVID-19 in intensive care unit (ICU); (2) Methods: This is a 3-month prospective observational study in a third-level COVID-19 hospital. The authors collected demographic, clinical, severity score and outcome data. Logistic regression analyses were performed to identify predictors of NHH; (3) Results: 156 COVID-19 patients were admitted to the ICU. The incidence of NHH was 12.2% (19 patients). The univariate analysis showed that invasive mechanical ventilation had a 6.6-fold higher risk (OR 6.66, 95% CI 0.86–51.6, p = 0.039) for NHH, while in the multiple regression analysis, there was a 7-fold higher risk for NHH—but it was not statistically significant (OR 7.1, 95% CI 0.90–56.4, p = 0.062). Demographics, clinical characteristics and mortality in the ICU at 28 days did not show a significant association with NHH. (4) Conclusions: The incidence of NHH in ICU COVID-19 patients was not low. NHH did not appear to significantly increase mortality, and all patients with non-hepatic hyperammonemia were successfully treated without further complications. However, the pathogenesis of NHH in ICU patients with COVID-19 remains a topic to be explored with further research. [ABSTRACT FROM AUTHOR]

Vitamin D plays a crucial role in many infectious diseases, such as tuberculosis (TB), that remains one of the world's top infectious killers with 1.5 million deaths from TB in 2021. Vitamin D suppresses the replication of Mycobacterium tuberculosis in vitro and showed a promising role in TB management as a result of its connection with oxidative balance. Our review encourages the possible in vivo benefit of a joint administration with other vitamins, such as vitamin A, which share a known antimycobacterial action with vitamin D. However, considering the low incidence of side effects even at high dosages and its low cost, it would be advisable to assess vitamin D level both in patients with active TB and high-risk groups and administer it, at least to reach sufficiency levels. [ABSTRACT FROM AUTHOR]

Background: There is conflicting evidence for how HIV influences COVID-19 infection. The aim of this study was to compare characteristics at presentation and the clinical outcomes of people living with HIV (PLWH) versus HIV-negative patients (non-PLWH) hospitalized with COVID-19. Methods: Primary endpoint: time until invasive ventilation/death. Secondary endpoints: time until ventilation/death, time until symptoms resolution. Results: A total of 1647 hospitalized patients were included (43 (2.6%) PLWH, 1604 non-PLWH). PLWH were younger (55 vs. 61 years) and less likely to be with PaO2/FiO2 < 300 mmHg compared with non-PLWH. Among PLWH, nadir of CD4 was 185 (75–322) cells/μL; CD4 at COVID-19 diagnosis was 272 cells/μL (127–468) and 77% of these were virologically suppressed. The cumulative probability of invasive mechanical ventilation/death at day 15 was 4.7% (95%CI 1.2–17.3) in PLWH versus 18.9% (16.9–21.1) in non-PLWH (p = 0.023). The cumulative probability of non-invasive/invasive ventilation/death at day 15 was 20.9% (11.5–36.4) in PLWH versus 37.6% (35.1–40.2) in non-PLWH (p = 0.044). The adjusted hazard ratio (aHR) of invasive mechanical ventilation/death of PLWH was 0.49 (95% CI 0.12–1.96, p = 0.310) versus non-PLWH; similarly, aHR of non-invasive/invasive ventilation/death of PLWH was 1.03 (95% CI 0.53–2.00, p = 0.926). Conclusion: A less-severe presentation of COVID-19 at hospitalization was observed in PLWH compared to non-PLWH; no difference in clinical outcomes could be detected. [ABSTRACT FROM AUTHOR]

• Mycobacterium tuberculosis (Mtb) DNA is detected in the peripheral blood cells of donors with tuberculosis (TB) or TB infection. • Mtb DNA is detected in the peripheral blood cells of donors with presumptive TB. • Mtb DNA detection is more frequent in peripheral CD34+ cells. • CD34+ cells may represent a niche for Mtb. • Mtb DNA in peripheral blood cells may be a new microbial biomarker. To investigate whether Mycobacterium tuberculosis (Mtb) DNA is detected in peripheral blood mononuclear cells (PBMC) of subjects with tuberculosis (TB) or TB infection (TBI) living in a low-burden country. We prospectively enrolled 57 patients with TB, 41 subjects with TBI, and 39 controls in Rome, Italy. PBMC were isolated, cluster of differentiation (CD)34+ and CD34− cells were immunomagnetic separated, DNA was extracted, and digital polymerase chain reaction for IS 6110 and rpoB sequences was used to detect Mtb DNA in PBMC subsets and unfractionated PBMC. We detected Mtb DNA at a low copy number in CD34+ cells in 4o f 30 (13%) patients with TB, 2 of 24 (8%) subjects with TBI, and 1 of 24 (4%) controls. Mtb DNA was detected in unfractionated PBMC in 3 of 51 (6%) patients with TB, 2 of 38 (5%) subjects with TBI, and 2 of 36 (6%) controls. In CD34− cells, only 1 of 31 (3%) subjects with TBI tested positive for Mtb DNA. Mtb DNA was detected at low frequencies and levels in the PBMC of subjects with TBI and donors with TB living in a low-burden country. In particular, Mtb DNA was detected more frequently in CD34+ cells, supporting the hypothesis that these cells may represent a Mtb niche. This finding informs biological understanding of Mtb pathogenesis and may support the development of a microbial blood biomarker for Mtb infection. [ABSTRACT FROM AUTHOR]

• TB and COVID-19 coinfection does not affect M. tuberculosis -specific response. • TB and COVID-19 coinfection limits the ability to in vitro respond to SARS-CoV-2. • Latent TB infection does not affect the ability to in vitro respond to SARS-CoV-2. The interaction of COVID-19 and tuberculosis (TB) are still poor characterized. Here we evaluated the immune response specific for Micobacterium tuberculosis (Mtb) and SARS-CoV-2 using a whole-blood-based assay-platform in COVID-19 patients either with TB or latent TB infection (LTBI). We evaluated IFN-γ level in plasma from whole-blood stimulated with Mtb antigens in the Quantiferon-Plus format or with peptides derived from SARS-CoV-2 spike protein, Wuhan-Hu-1 isolate (CD4-S). We consecutively enrolled 63 COVID-19, 10 TB-COVID-19 and 11 LTBI-COVID-19 patients. IFN-γ response to Mtb-antigens was significantly associated to TB status and therefore it was higher in TB-COVID-19 and LTBI-COVID-19 patients compared to COVID-19 patients (p ≤ 0.0007). Positive responses against CD4-S were found in 35/63 COVID-19 patients, 7/11 LTBI-COVID-19 and only 2/10 TB-COVID-19 patients. Interestingly, the responders in the TB-COVID-19 group were less compared to COVID-19 and LTBI-COVID-19 groups (p = 0.037 and 0.044, respectively). Moreover, TB-COVID-19 patients showed the lowest quantitative IFN-γ response to CD4-S compared to COVID-19-patients (p = 0.0336) and LTBI-COVID-19 patients (p = 0.0178). Our data demonstrate that COVID-19 patients either TB or LTBI have a low ability to build an immune response to SARS-CoV-2 while retaining the ability to respond to Mtb-specific antigens. [ABSTRACT FROM AUTHOR]

Background: Several biomarkers have been identified to predict the outcome of COVID-19 severity, but few data are available regarding sex differences in their predictive role. Aim of this study was to identify sex-specific biomarkers of severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19. Methods: Plasma levels of sex hormones (testosterone and 17β-estradiol), sex-hormone dependent circulating molecules (ACE2 and Angiotensin1-7) and other known biomarkers for COVID-19 severity were measured in male and female COVID-19 patients at admission to hospital. The association of plasma biomarker levels with ARDS severity at admission and with the occurrence of respiratory deterioration during hospitalization was analysed in aggregated and sex disaggregated form. Results: Our data show that some biomarkers could be predictive both for males and female patients and others only for one sex. Angiotensin1-7 plasma levels and neutrophil count predicted the outcome of ARDS only in females, whereas testosterone plasma levels and lymphocytes counts only in males. Conclusions: Sex is a biological variable affecting the choice of the correct biomarker that might predict worsening of COVID-19 to severe respiratory failure. The definition of sex specific biomarkers can be useful to alert patients to be safely discharged versus those who need respiratory monitoring. [ABSTRACT FROM AUTHOR]

Introduction: It was usually assumed that pulmonary tuberculosis (TB) in HIV-seropositive patients represents reactivation TB, despite the radiographic appearance frequently consistent rather with a recent disease. Hence, these radiographic features were considered "atypical". We have hypothesised that the so called "atypical" radiographic features could be due to a greater proportion of primary TB among these patients, representing the typical appearance of primary radiological pattern. Material and Methods: We reviewed chest imaging of 219 HIV+ patients with microbiological proven pulmonary tuberculosis, who were assessed for the presence, number, distribution of cavitations and for associated pulmonary parenchymal abnormalities, adenopathies and pleural effusion, and were classified as a primary or post-primary pattern. Results: The patients with post-primary pattern were 50%, and the rate of cavitation was 63%, not wandering off the general population. Cavities still occurred with similar proportion in groups with CD4 <200 or >200cells/mm(3). Conclusion: We suggest that HIV-related pulmonary tuberculosis is typical in its radiological appearances, consistent with those of the general population, and this could be confirmed by the most recent molecular epidemiological techniques that allow to definitely classify the tuberculosis episodes as either primary or post-primary disease. [ABSTRACT FROM AUTHOR]

Nanostructured materials are attracting increased interest and applications. Exciting perspectives may be offered by electrical insulation. Polymeric nanofilled materials may find new and/or upgraded applications in the electrical and electronic industry, replacing conventional insulation to provide improved performances in electrical apparatus, as regards, e.g., reliability, environmental compatibility and power rating. This paper shows that electrical properties of nanocomposite insulating materials for dc applications, specifically space charge, conductivity and breakdown voltage, can improve significantly with respect to the basis, unfilled materials. Reference is made to two polymeric materials, i.e. poly(ethylene-co- vinylacetate) (EVA) and polypropylene (PP), that are widely used as electrical insulation, e.g. for cables and capacitors. The nanofiller consists of an organophilic layered silicate, speéiflcally an extra-pure synthetic fluorohectorite modified by means of interlayer exchange of sodium cations for protonated octadecylamine Nut (0DM, in a weight concentration of maximum 6%. In both materials the space charge accumulation rate as a function of applied electric field is significantly reduced, while the electrical conductivity is raised. The breakdown voltage can increase for the nanofilled materials. [ABSTRACT FROM AUTHOR]

Reports on a study on primary pulmonary hypertension in HIV patients. Determination of the relationship between degree of pulmonary hypertension and conditions, such as HIV risk factor, degree of immunosuppression, presence or absence of AIDS and presence or absence of liver cirrhosis; Use of the Medline and Aidsline databases from 1987 to 1998.

• The prognosis of coronavirus diseases 2019 (COVID-19) is gender-related. • TMPRSS2 plays a key role in COVID-19; androgen receptor regulates its expression. • Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can damage the testes. • Low serum testosterone at diagnosis is predictive of severe COVID-19. • Low serum testosterone predicts for longer hospitalization and hyperinflammation. To investigate the association between sex hormones and the severity of coronavirus disease 2019 (COVID-19). Furthermore, associations between sex hormones and systemic inflammation markers, viral shedding and length of hospital stay were studied. This case–control study included a total of 48 male patients with COVID-19 admitted to an Italian reference hospital. The 24 cases were patients with PaO 2 /FiO 2 <250 mmHg and who needed ventilatory support during hospitalization (severe COVID-19). The 24 controls were selected in a 1:1 ratio, matched by age, from patients who maintained PaO 2 /FiO 2 >300 mmHg at all times and who may have required low-flow oxygen supplementation during hospitalization (mild COVID-19). For each group, sex hormones were evaluated on hospital admission. Patients with severe COVID-19 (cases) had a significantly lower testosterone level compared with patients with mild COVID-19 (controls). Median total testosterone (TT) was 1.4 ng/mL in cases and 3.5 ng/mL in controls (P = 0.005); median bioavailable testosterone (BioT) was 0.49 and 1.21 in cases and controls, respectively (P = 0.008); and median calculated free testosterone (cFT) was 0.029 ng/mL and 0.058 ng/mL in cases and controls, respectively (P = 0.015). Low TT, low cFT and low BioT were correlated with hyperinflammatory syndrome (P = 0.018, P = 0.048 and P = 0.020, respectively) and associated with longer length of hospital stay (P = 0.052, P = 0.041 and P = 0.023, respectively). No association was found between sex hormone level and duration of viral shedding, or between sex hormone level and mortality rate. A low level of testosterone was found to be a marker of clinical severity of COVID-19. [ABSTRACT FROM AUTHOR]

Background: Recent studies proposed the whole-blood based IFN-γ-release assay to study the antigen-specific SARS-CoV-2 response. Since the early prediction of disease progression could help to assess the optimal treatment strategies, an integrated knowledge of T-cell and antibody response lays the foundation to develop biomarkers monitoring the COVID-19. Whole-blood-platform tests based on the immune response detection to SARS-CoV2 peptides is a new approach to discriminate COVID-19-patients from uninfected-individuals and to evaluate the immunogenicity of vaccine candidates, monitoring the immune response in vaccine trial and supporting the serological diagnostics results. Here, we aimed to identify in the whole-blood-platform the best immunogenic viral antigen and the best immune biomarker to identify COVID-19-patients.Methods: Whole-blood was overnight-stimulated with SARS-CoV-2 peptide pools of nucleoprotein-(NP) Membrane-, ORF3a- and Spike-protein. We evaluated: IL-1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL- 15, IL-17A, eotaxin, FGF, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF, RANTES, TNF-α, VEGF. By a sparse partial least squares discriminant analysis we identified the most important soluble factors discriminating COVID-19- from NO-COVID-19-individuals.Results: We identified a COVID-19 signature based on six immune factors: IFN-γ, IP-10 and IL-2 induced by Spike; RANTES and IP-10 induced by NP and IL-2 induced by ORF3a. We demonstrated that the test based on IP-10 induced by Spike had the highest AUC (0.85, p  <  0.0001) and that the clinical characteristics of the COVID-19-patients did not affect IP-10 production. Finally, we validated the use of IP-10 as biomarker for SARS-CoV2 infection in two additional COVID-19-patients cohorts.Conclusions: We set-up a whole-blood assay identifying the best antigen to induce a T-cell response and the best biomarkers for SARS-CoV-2 infection evaluating patients with acute COVID-19 and recovered patients. We focused on IP-10, already described as a potential biomarker for other infectious disease such as tuberculosis and HCV. An additional application of this test is the evaluation of immune response in SARS-CoV-2 vaccine trials: the IP-10 detection may define the immunogenicity of a Spike-based vaccine, whereas the immune response to the virus may be evaluated detecting other soluble factors induced by other viral-antigens. [ABSTRACT FROM AUTHOR]

• Retrospective analysis of 536 patients hospitalized with COVID-19. • Median duration of viral shedding from symptoms onset was 18 days. • Severity, comorbidities and inflammatory markers negatively predict viral clearance. • Viral clearance doubled recovery chance and reduced the probability of death/ventilation. • Prompt hospitalization indicated for patients with severe disease or comorbidities. Limited data are available about the predictors and outcomes associated with prolonged SARS-CoV-2 RNA shedding (VS). A retrospective study including COVID-19 patients admitted to an Italian hospital between March 1 and July 1, 2020. Predictors of viral clearance (VC) and prolonged VS from the upper respiratory tract were assessed by Poisson regression and logistic regression analyses. The causal relation between VS and clinical outcomes was evaluated through an inverse probability weighted Cox model. The study included 536 subjects. The median duration of VS from symptoms onset was 18 days. The estimated 30-day probability of VC was 70.2%. Patients with comorbidities, lymphopenia at hospital admission, or moderate/severe respiratory disease had a lower chance of VC. The development of moderate/severe respiratory failure, delayed hospital admission after symptoms onset, baseline comorbidities, or D-dimer >1000 ng/mL at admission independently predicted prolonged VS. The achievement of VC doubled the chance of clinical recovery and reduced the probability of death/mechanical ventilation. Respiratory disease severity, comorbidities, delayed hospital admission and inflammatory markers negatively predicted VC, which resulted to be associated with better clinical outcomes. These findings highlight the importance of prompt hospitalization of symptomatic patients, especially where signs of severity or comorbidities are present. [ABSTRACT FROM AUTHOR]

• Pro-inflammatory factors play a central role in COVID-19 severity and mortality. • Down Syndrome is characterised by immune dysregulation and respiratory infections. • Down Syndrome patients with COVID-19 are at high risk of an unfavourable outcome. We report two cases of Corona Virus Disease-19 (COVID-19) in patients with Down Syndrome (DS) and describe the identification, diagnosis, clinical course and management of the infection. Down Syndrome, which is caused by trisomy 21, is characterized by immune dysregulation, anatomical differences in the upper respiratory tract and higher rate of comorbidities. All these risk factors can contribute to more severe clinical presentations of COVID-19 in this population. It is essential to raise awareness of the clinical relevance of SARS-COV-2 infection in DS patients, as well as in other most vulnerable patients, in order to improve their management and treatment and to encourage vaccinating these individuals early, once a vaccination is available. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) is mainly a respiratory tract disease and acute respiratory failure with diffuse microvascular pulmonary thrombosis are critical aspects of the morbidity and mortality of this new syndrome. Purpose: The aim of our study was to investigate, in severe COVID-19 hospitalized patients, the P-selectin plasma concentration as a biomarker of endothelial dysfunction and platelet activation. Methods: 46 patients with severe or critical SARS-CoV-2 infection were included in the study. Age-matched patients then were divided in those requiring admission to the intensive care unit (ICU, ICU cases) vs those not requiring ICU hospitalization (non-ICU cases). Blood samples of severe COVID-19 patients were collected at the time of hospital admission. The quantification of soluble P-selectin was performed by ELI, assay. Results: Our study showed a higher P-selectin plasma concentration in patients with Covid-19, regardless of ICU admission, compared to the normal reference values and compared to ten contextually sampled healthy donors (HD); (COVID-19): median 65.2 (IQRs: 45.1-81.1) vs. HD: 40.3 (IQRs: 24.3-48.7), p=0023. Moreover, results showed a significant reduction of P-sele din after platelets removal in HD, in contrast, both ICU and non-ICU COVID-19 patients showed similar high levels of P-selectin with and without platelets. Conclusion: Elevation of P-selectin suggests a central role of platelet endothelium interaction as part of the multifaced pathogenic mechanism of COVID-19 leading to the local activation of hemostatic system forming pulmonary thrombi. Further work is necessary to determine the therapeutic role of antiplatelets agents or of the anti P-selectin antibody Crizanlizumab. [ABSTRACT FROM AUTHOR]

Background: Detailed temporal analyses of complete (full) blood count (CBC) parameters, their evolution and relationship to patient age, gender, co-morbidities and management outcomes in survivors and non-survivors with COVID-19 disease, could identify prognostic clinical biomarkers. Methods: From 29 January 2020 until 28 March 2020, we performed a longitudinal cohort study of COVID-19 inpatients at the Italian National Institute for Infectious Diseases, Rome, Italy. 9 CBC parameters were studied as continuous variables [neutrophils, lymphocytes, monocytes, platelets, mean platelet volume, red blood cell count, haemoglobin concentration, mean red blood cell volume and red blood cell distribution width (RDW %)]. Model-based punctual estimates, as average of all patients' values, and differences between survivors and non-survivors, overall, and by co-morbidities, at specific times after symptoms, with relative 95% CI and P-values, were obtained by marginal prediction and ANOVA- style joint tests. All analyses were carried out by STATA 15 statistical package. Main findings: 379 COVID-19 patients [273 (72% were male; mean age was 61.67 (SD 15.60)] were enrolled and 1,805 measures per parameter were analysed. Neutrophils' counts were on average significantly higher in non-survivors than in survivors (P<0.001) and lymphocytes were on average higher in survivors (P<0.001). These differences were time dependent. Average platelets' counts (P<0.001) and median platelets' volume (P<0.001) were significantly different in survivors and non-survivors. The differences were time dependent and consistent with acute inflammation followed either by recovery or by death. Anaemia with anisocytosis was observed in the later phase of COVID-19 disease in non-survivors only. Mortality was significantly higher in patients with diabetes (OR = 3.28; 95%CI 1.51–7.13; p = 0.005), obesity (OR = 3.89; 95%CI 1.51–10.04; p = 0.010), chronic renal failure (OR = 9.23; 95%CI 3.49–24.36; p = 0.001), COPD (OR = 2.47; 95% IC 1.13–5.43; p = 0.033), cardiovascular diseases (OR = 4.46; 95%CI 2.25–8.86; p = 0.001), and those >60 years (OR = 4.21; 95%CI 1.82–9.77; p = 0.001). Age (OR = 2.59; 95%CI 1.04–6.45; p = 0.042), obesity (OR = 5.13; 95%CI 1.81–14.50; p = 0.002), renal chronic failure (OR = 5.20; 95%CI 1.80–14.97; p = 0.002) and cardiovascular diseases (OR 2.79; 95%CI 1.29–6.03; p = 0.009) were independently associated with poor clinical outcome at 30 days after symptoms' onset. Interpretation: Increased neutrophil counts, reduced lymphocyte counts, increased median platelet volume and anaemia with anisocytosis, are poor prognostic indicators for COVID19, after adjusting for the confounding effect of obesity, chronic renal failure, COPD, cardiovascular diseases and age >60 years. [ABSTRACT FROM AUTHOR]

Background: Descriptions of the pathological features of coronavirus disease-2019 (COVID-19) caused by the novel zoonotic pathogen severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emanate from tissue biopsies, case reports, and small postmortem studies restricted to the lung and specific organs. Whole-body autopsy studies of COVID-19 patients have been sparse.Methods: To further define the pathology caused by SARS-CoV-2 across all body organs, we performed autopsies on 22 patients with COVID-19 (18 with comorbidities and 4 without comorbidities) who died at the National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS Hospital, Rome, Italy. Tissues from the lung, heart, liver, kidney, spleen, and bone marrow (but not the brain) were examined. Only lung tissues were subject to transmission electron microscopy.Results: COVID-19 caused multisystem pathology. Pulmonary and cardiovascular involvement were dominant pathological features. Extrapulmonary manifestations included hepatic, kidney, splenic, and bone marrow involvement, and microvascular injury and thrombosis were also detected. These findings were similar in patients with or without preexisting medical comorbidities.Conclusions: SARS-CoV-2 infection causes multisystem disease and significant pathology in most organs in patients with and without comorbidities. [ABSTRACT FROM AUTHOR]

The impact of tuberculosis and of anti-tuberculosis therapy on composition and modification of human lung microbiota has been the object of several investigations. However, no clear outcome has been presented so far and the relationship between M. tuberculosis pulmonary infection and the resident lung microbiota remains vague. In this work we describe the results obtained from a multicenter study of the microbiota of sputum samples from patients with tuberculosis or unrelated lung diseases and healthy donors recruited in Switzerland, Italy and Bangladesh, with the ultimate goal of discovering a microbiota-based biomarker associated with tuberculosis. Bacterial 16S rDNA amplification, high-throughput sequencing and extensive bioinformatic analyses revealed patient-specific flora and high variability in taxon abundance. No common signature could be identified among the individuals enrolled except for minor differences which were not consistent among the different geographical settings. Moreover, anti-tuberculosis therapy did not cause any important variation in microbiota diversity, thus precluding its exploitation as a biomarker for the follow up of tuberculosis patients undergoing treatment. [ABSTRACT FROM AUTHOR]

On January 9 2020, the World Health Organization (WHO) declared the identification, by Chinese Health authorities, of a novel coronavirus, further classified as SARS-CoV-2 responsible of a disease (COVID-19) ranging from asymptomatic cases to severe respiratory involvement. On March 9 2020, WHO declared COVID-19 a global pandemic. Italy is the second most affected country by COVID-19 infection after China. The "L. Spallanzani" National Institute for the Infectious Diseases, IRCCS, Rome, Italy, has been the first Italian hospital to admit and manage patients affected by COVID-19. Hereby, we show our recommendations for the management of COVID-19 patients, based on very limited clinical evidences; they should be considered as expert opinions, which may be modified according to newly produced literature data. [ABSTRACT FROM AUTHOR]

Rationale: Treatment of multi-drug resistant Tuberculosis (MDR-TB) is challenging because it mostly relies on drugs with lower efficacy and greater toxicity than those used for drug-susceptible TB. Objectives: Aim of the study was to describe the frequency and type of adverse drug reactions in a cohort of MDR-TB patients and their potential impact on treatment outcome. Methods: We conducted a retrospective study in a cohort of MDR-TB patients enrolled at a tertiary referral hospital in Italy from January 2008 to December 2016. The records of patients were reviewed for epidemiological, clinical, microbiological and adverse drug reactions data. Results: Seventy-four MDR-TB patients (mean age 32 years, 58.1% males, 2 XDR, 12 pre-XDR TB) were extracted from the Institute data base and included in the retrospective study cohort in the evaluation period (January 2008—December 2016). Median length of treatment duration was 20 months (IQR 14–24). Treatment outcome was successful in 57 patients (77%; 51 cured, 6 treatment completed); one patient died and one failed (2.7% overall); 15 patients were lost to follow-up (20.3%). Sixty-six (89.2%) presented adverse drug reactions during the whole treatment period. Total number of adverse drug reactions registered was 409. Three hundred forty-six (84.6%) were classified as adverse events (AEs) and 63 (15.4%) were serious AEs (SAEs). One third of the total adverse drug reactions (134/409; 32.8%) was of gastrointestinal origin, followed by 47/409 (11.5%) ototoxic drug reactions, thirty-five (8.6%) regarded central nervous system and 33 (8.1%) affected the liver. All 63 SAEs required treatment suspension with 61 SAEs out of 63 (96.8%) occurring during the first six months of treatment. Factors associated with unsuccessful treatment outcome were smoking (p = 0.039), alcohol abuse (p = 0.005) and homeless condition (p = 0.044). Neither the number of antitubercular drugs used in different combinations nor the number of AEs showed significant impact on outcome. Patients who completed the treatment experienced a greater number of AEs and SAEs (p < 0.001) if compared to lost to follow-up patients. Conclusions: Our data demonstrate that, despite the high frequency of adverse drug reactions and long term therapy, the clinical management of MDR-TB patients in a referral center could reach successful treatment according to WHO target, by implementing active and systematic clinical and laboratory assessment to detect, report and manage suspected and confirmed adverse drug reactions. [ABSTRACT FROM AUTHOR]

This paper discusses the charge transport and accumulation in clay-containing LDPE (low density polyethylene) nanocomposites. LDPE is shown to host charges of both polarities in the form of homo and heterocharge when subjected to high electric fields. The addition of nanoclays has been shown to always increase the high field DC conductivity of the nanocomposites. This is shown to actually work in favor of the ability of the material to prevent the accumulation of space charge by slowly, but persistently, allowing space charges to flow across the insulation wall. However, in severe conditions of a combined high electric field and high temperature, the current flow exceeds a threshold where massive injected charges negatively impact the charge profile and the electric field distribution is greatly distorted. [ABSTRACT FROM AUTHOR]

Highlights • New biomarkers are needed to control tuberculosis (TB). • Agonist and antagonist forms of IP-10 are measurable in urine. • IP-10 levels associate with both TB and pneumonia disease, suggesting that they associate with acute inflammation. • Urine IP-10 decreases at TB therapy completion; further studies are needed to evaluate if useful for TB monitoring efficacy. Abstract Objectives Biomarkers for tuberculosis (TB) diagnosis and clinical management are needed to defeat TB. In chronic hepatitis, patients not responding to interferon/ribavirin treatment had high levels of an antagonist form of IP-10. Recently, antagonist IP-10 has been shown to be involved also in TB pathogenesis. Here, we investigated IP-10 agonist/antagonist forms as potential inflammatory biomarkers to support TB diagnosis and monitoring. Methods Total IP-10 and its agonist/antagonist forms were measured by SIMOA digital ELISA in urine obtained from patients with active TB at baseline and after treatment. Healthy donors (HD) and patients with pneumonia were enrolled as controls. Results Patients with active TB had significantly higher levels of total and agonist IP-10 at baseline compared to HD; conversely, no differences were observed between IP-10 levels in active TB vs pneumonia. Moreover, in active TB a decline of total urine IP-10 was observed at therapy completion; agonist/antagonist forms reflected this decline although their differences were not statistically significant. Conclusions We showed for the first time that agonist/antagonist IP-10 forms are measurable in urine. IP-10 levels associate with TB and pneumonia disease, suggesting their association with acute inflammation. Further studies are needed to assess their role to monitor TB treatment efficacy. [ABSTRACT FROM AUTHOR]

• Collection of throat swabs is not a standardized procedure, and caution should be taken if negative result is taken as the criterion for the exclusion of SARS-CoV-2 infection • Nasopharyngeal swabs may result negative for SARS-CoV-2 in patients with lung infiltrates • RT-PCR for SARS-CoV-2 in lower respiratory samples may help diagnosis • Healthcare workers should perform aerosol-generating procedures in an adequately ventilated room and should wear adequate PPE. To report a clinical case of a patient with a compatible HRCT scan and two negative SARS-CoV-2 RNA upper respiratory tract specimens but with a confirmed viral infection by BAL (19 days after symptom onset). Revision of a patient's clinical charts with COVID-19 admitted at INMI L. Spallanzani Hospital Two oropharyngeal swab tests of SARS-CoV-2 by qualitative real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay were performed at admission (17 days from symptoms onset) and a day apart and were found negative. BAL fluid collected 19 days after symptoms onset was positive for SARS-CoV-2. This case highlights importance of clinical suspicion of SARS-CoV-2 infection in diagnosis and infectivity assessment. We suggest collection of BAL fluid when consecutive nasopharyngeal swabs are negative, to confirm or exclude the diagnosis of COVID-19-associated pneumonia. Healthcare workers should perform aerosol-generating procedures in an adequately ventilated room and should wear adequate PPE. [ABSTRACT FROM AUTHOR]

Action on social determinants is a main component of the World Health Organization End Tuberculosis (TB) Strategy. The aim of the study was to collect information on socioeconomic characteristics and biomedical risk factors in migrant TB patients in Italy and compare it with data collected among Italian TB patients. A cross-sectional study was conducted among TB patients aged ≥18 years over a 12-months enrolment period in 12 major Italian hospitals. Information on education, employment, housing and income was collected, and European Union Statistics on Income and Living Conditions index was used to assess material deprivation. Among migrants, we also analyzed factors associated with severe material deprivation. Migrants were compared with younger (18–64 years) and older (65+ years) Italians patients. Out of 755 patients enrolled (with a median age of 42 years, interquartile range: 31–53), 65% were migrants. Pulmonary, microbiologically confirmed, and new cases were 80%, 73%, and 87% respectively. Prevalence of co-morbidities (i.e. diabetes, chronic kidney disease, neoplastic diseases and use of immunosuppressive drugs) was lower among migrants compared to Italian TB patients, while indicators of socioeconomic status, income and housing conditions were worst in migrants. Forty-six percent of migrants were severely deprived vs. 9% of Italians (p<0.0001, 11.3% and 5.5% among younger and older Italians, respectively). Among migrants, being male, older, irregular, unemployed, with a shorter time spent in Italy, a lower education level, and without a co-morbidity diagnosis were factors associated with severe material deprivation at multi-variable logistic regression. Moreover, socioeconomic indicators for Italian patients did not differ from those reported for the general Italian population, while migrant TB patients seem to have a higher prevalence of severe material deprivation than other migrants residing in Italy. Intervention to address the needs of this population are urgent. [ABSTRACT FROM AUTHOR]

Summary The convergence between tuberculosis (TB) and diabetes mellitus (DM) will represent a major public health challenge in the near future. DM increases the risk of developing TB by two to three times and also increases the risk of TB treatment failure, relapse, and death. The global prevalence of DM is predicted to rise significantly in the next two decades, particularly in some of the low- and middle-income countries with the highest TB burden. Migration may add further complexity to the effort to control the impact on TB of the growing DM pandemic. Migration may increase the risk of DM, although the magnitude of this association varies according to country of origin and ethnic group, due to genetic factors and lifestyle differences. Migrants with TB may have an increased prevalence of DM compared to the native population, and the risk of TB among persons with DM may be higher in migrants than in autochthonous populations. Screening for DM among migrants, screening migrants with DM for active and latent TB, and improving access to DM care, could contribute to mitigate the effects of DM on TB. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is one of the most important cause of morbidity and death among infectious diseases, and continuous efforts are needed to improve diagnostic tools and therapy. Previous published studies showed that the absolute cells number of monocytes or lymphocytes in peripheral blood or yet the ratio of monocytes to lymphocytes displayed the ability to predict the risk of active TB. In the present study we evaluated the ratio of monocytes to lymphocytes variation and we also analyzed the ex-vivo expression of CD64 on monocytes as tools to identify biomarkers for discriminating TB stages. Significant differences were found when the average ratio of monocytes to lymphocytes of active TB patients was compared with latent TB infection (LTBI) subjects, cured TB and healthy donors (HD). By the receiver operator characteristics (ROC) curve analysis the cut-off value of 0.285, allowed the discrimination of active TB from HD, with a sensitivity of 91.04% and a specificity of 93.55% (95% of confidence interval: 0.92–0.99). The ROC curve analysis comparing TB patients and LTBI groups, led to a sensitivity and the specificity of the assay of 85.07% and 85.71%, respectively (95% of confidence interval: 0.85 to 0.96). The upregulation of CD64 expression on circulating monocytes in active TB patients could represent an additional biomarker for diagnosis of active TB. In conclusion, we found that the ML ratio or monocyte absolute count or phenotypic measures show predictive value for active TB. [ABSTRACT FROM AUTHOR]

Highlights • Tuberculin skin test (TST) is over a century old but it continues to be used widely. • When IGRAs were introduced it was anticipated that they would rapidly replace TST. • Neither TST nor IGRAs have a high accuracy for predicting active TB. • Latest WHO recommendations are that either TST or IGRA can be used to test for LTBI. • TST will be clinically useful until more accurate tests become available. Abstract Objective To make an informed viewpoint on the usefulness of Tuberculin Skin test (TST) compared to Interferon Gamma Release Assays (IGRAs) for diagnosis of Latent TB Infection (LTBI) in different geographical settings. Methods We reviewed the current literature on TST compared to IGRA, including national implementation of WHO LTBI recommendations and retrospective data over the past 7 years at the National Institute for Infectious Diseases "L. Spallanzani" as indirect indicator of usage of both tests under actual programmatic conditions. Results Current national guidelines vary considerably, reflecting the uncertainty and rapidly evolving evidence about the potential use of these tests. Data from Institute "L. Spallanzani" showed IGRA concordance in TST positive subjects only in 54.74% of subjects, while there was strong concordance between two tests in TST negative subjects (93.78%). Conclusion Neither IGRAs nor TST can distinguish active TB from LTBI. TST will continue to be clinically useful in low and high TB endemic areas until more accurate and predictive tests will become available. Clinical judgment remains fundamental in choosing between IGRA/TST tests and interpreting their results. [ABSTRACT FROM AUTHOR]

B-cells not only produce immunoglobulins and present antigens to T-cells, but also additional key roles in the immune system. Current knowledge on the role of B-cells in infections caused by intracellular bacteria is fragmentary and contradictory. We therefore analysed the phenotypical and functional properties of B-cells during infection and disease caused by Mycobacterium tuberculosis (Mtb), the bacillus causing tuberculosis (TB), and included individuals with latent TB infection (LTBI), active TB, individuals treated successfully for TB, and healthy controls. Patients with active or treated TB disease had an increased proportion of antibodies reactive with mycobacteria. Patients with active TB had reduced circulating B-cell frequencies, whereas only minor increases in B-cells were detected in the lungs of individuals deceased from TB. Both active TB patients and individuals with LTBI had increased relative fractions of B-cells with an atypical phenotype. Importantly, these B-cells displayed impaired proliferation, immunoglobulin- and cytokine- production. These defects disappeared upon successful treatment. Moreover, T-cell activity was strongest in individuals successfully treated for TB, compared to active TB patients and LTBI subjects, and was dependent on the presence of functionally competent B-cells as shown by cellular depletion experiments. Thus, our results reveal that general B-cell function is impaired during active TB and LTBI, and that this B-cell dysfunction compromises cellular host immunity during Mtb infection. These new insights may provide novel strategies for correcting Mtb infection-induced immune dysfunction towards restored protective immunity. [ABSTRACT FROM AUTHOR]

Treatment of multidrug-resistant tuberculosis (MDR-TB) cases is challenging because it relies on second-line drugs that are less potent and more toxic than those used in the clinical management of drug-susceptible TB. Moreover, treatment outcomes for MDR-TB are generally poor compared to drug sensitive disease, highlighting the need for of new drugs. For the first time in more than 50 years, two new anti-TB drugs were approved and released. Bedaquiline is a first-in-class diarylquinoline compound that showed durable culture conversion at 24 weeks in phase IIb trials. Delamanid is the first drug of the nitroimidazole class to enter clinical practice. Similarly to bedaquiline results of phase IIb studies showed increased sputum-culture conversion at 2 months and better final treatment outcomes in patients with MDR-TB. Among repurposed drugs linezolid and carbapenems may represent a valuable drug to treat cases of MDR and extensively drug-resistant TB. The recommended regimen for MDR-TB is the combination of at least four drugs to which M. tuberculosis is likely to be susceptible for the duration of 20 months. Drugs are chosen with a stepwise selection process through five groups on the basis of efficacy, safety, and cost. Clinical phase III trials on new regimen are ongoing that could prove transformative against MDR-TB, by being shorter (six months), simpler (an all-oral regimen) and safer than current standard therapy. It is fundamental that the adoption of the new drugs is done responsibly to avoid inappropriate use. Concentration of inpatient MDR-TB treatment in specialized centers could be considered in countries with low numbers of cases in order to provide appropriate clinical case management and to prevent emergence of drug resistance. [ABSTRACT FROM AUTHOR]

In Italy tuberculosis (TB) is largely concentrated in vulnerable groups such as migrants and in urban settings. We analyzed three TB case finding interventions conducted at primary centers and mobile clinics for regular/irregular immigrants and refugees/asylum seekers performed over a four-year period (November 2009-March 2014) at five different sites in Rome and one site in Milan, Italy. TB history and presence of symptoms suggestive of active TB were investigated by verbal screening through a structured questionnaire in migrants presenting for any medical condition to out-patient and mobile clinics. Individuals reporting TB history or symptoms were referred to a TB clinic for diagnostic workup. Among 6347 migrants enrolled, 891 (14.0%) reported TB history or symptoms suggestive of active TB and 546 (61.3%) were referred to the TB clinic. Of them, 254 (46.5%) did not present for diagnostic evaluation. TB was diagnosed in 11 individuals representing 0.17% of those screened and 3.76% of those evaluated. The overall yield of this intervention was in the range reported for other TB screening programs for migrants, although we recorded an unsatisfactory adherence to diagnostic workup. Possible advantages of this intervention include low cost and reduced burden of medical procedures for the screened population. [ABSTRACT FROM AUTHOR]

Blood-based biomarkers tests are attractive alternative for diagnosing tuberculosis to assays depending on mycobacteria detection. Given several immunological markers we used logistic regression to model the probability of active tuberculosis in a cohort of patients with active or latent tuberculosis, showing an increased accuracy in distinguishing active from latent tuberculosis. [ABSTRACT FROM AUTHOR]

Background: The prevalence of chronic hepatitis C virus (HCV) infection in the Italian correctional population is estimated to be around 38%. In this setting HCV infection treatment is controversial because of several factors such as active drug substance abuse, psychiatric illness, length of treatment, risk of re-infection, poor adherence and low success rate.Methods: A retrospective data review of 159 inmates, positive for anti-Hepatitis C virus (HCV) antibody, evaluated to National Institute for Infectious Diseases "L. Spallanzani" (INMI) from January 2006 to December 2009, was conducted to evaluate rate of completion (feasibility) and outcome efficacy of chronic Hepatitis C Virus (HCV) infection treatment with Pegylated Interferon and Ribavirin in five correctional facilities in Rome.Results: Of the 159 inmates evaluated in the study period, 50, all male (median age 39 years) were treated. Twenty patients (40%) did not complete treatment: 15 showed no response and therapy was stopped, 5 patients (10%) interrupted treatment because of adverse reactions. The global feasibility was 60%. The overall sustained virologic response (SVR) was 50% (32% for genotype 1 and 68% for genotype other than 1). The main predictors of SVR at the Multivariable Logistic Regression Odds Ratio (MLR-OR) were a better pretreatment histological diagnosis (absence of bridging fibrosis or cirrhosis [MLR-OR 11.85; 95% CI 1.96-71.62) and a HCV genotype other than 1 (MLR-OR 5.87; 95% CI 1.49-23.17).Conclusions: Chronic HCV infection treatment in correctional facilities is feasible and effective and should be strongly recommended, in combination with preventive measures, in appropriately screened patients because it represents an important opportunity to treat a population with a high prevalence of chronic HCV infection among whom treatment options post incarceration may be limited. [ABSTRACT FROM AUTHOR]

(1) Background: COVID-19 is a novel cause of acute respiratory distress syndrome (ARDS). Indeed, with the increase of ARDS cases due to the COVID-19 pandemic, there has also been an increase in the incidence of cases with pneumothorax (PNX) and pneumomediastinum (PNM). However, the incidence and the predictors of PNX/PMN in these patients are currently unclear and even conflicting. (2) Methods: The present observational study analyzed the incidence of barotrauma (PNX/PNM) in COVID-19 patients with moderate–severe ARDS hospitalized in a year of the pandemic, also focusing on the three waves occurring during the year, and treated with positive-pressure ventilation (PPV). We collected demographic and clinical data. (3) Results: During this period, 40 patients developed PNX/PNM. The overall incidence of barotrauma in all COVID-19 patients hospitalized in a year was 1.6%, and in those with moderate–severe ARDS in PPV was 7.2% and 3.8 events per 1000 positive-pressure ventilator days. The incidence of barotrauma in moderate–severe ARDS COVID-19 patients during the three waves was 7.8%, 7.4%, and 8.7%, respectively. Treatment with noninvasive respiratory support alone was associated with an incidence of barotrauma of 9.1% and 2.6 events per 1000 noninvasive ventilator days, of which 95% were admitted to the ICU after the event, due to a worsening of respiratory parameters. The incidence of barotrauma of ICU COVID-19 patients in invasive ventilation over a year was 5.8% and 2.7 events per 1000 invasive ventilator days. There was no significant difference in demographics and clinical features between the barotrauma and non-barotrauma group. The mortality was higher in the barotrauma group (17 patients died, 47.2%) than in the non-barotrauma group (170 patients died, 37%), although this difference was not statistically significant (p = 0.429). (4) Conclusions: The incidence of PNX/PNM in moderate–severe ARDS COVID-19 patients did not differ significantly between the three waves over a year, and does not appear to be very different from that in ARDS patients in the pre-COVID era. The barotrauma does not appear to significantly increase mortality in COVID-19 patients with moderate–severe ARDS if protective ventilation strategies are applied. Attention should be paid to the risk of barotrauma in COVID-19 patients in noninvasive ventilation because the event increases the probability of admission to the intensive care unit (ICU) and intubation. [ABSTRACT FROM AUTHOR]

Simple Summary: Image-guided biopsy of suspicious findings at mammography or breast ultrasonography can result in the diagnosis of lesions with uncertain malignant potential (B3 lesions). These, in turn, can turn out to be cancer (i.e., they are upgraded) when larger specimens of tissue are examined after breast surgery, especially if these lesions belong to the B3b subcategory, characterized by a higher probability of malignancy than the B3a subcategory. This uncertain nature makes their management highly controversial. We aimed to report a particularly large series of B3 lesions—coming from an internationally certified Breast Unit—since such series are seldom available. In this series of 3634 consecutive biopsies, we found 604 B3 lesions, of which 17 (2.8%) were upgraded to malignancy after surgery. B3b lesions had an almost 12-fold higher upgrade rate (4.7%) than B3a lesions (0.4%), reinforcing the evidence that recommends surgery for B3b lesions and acknowledges the possibility of active surveillance of B3a lesions. The rate of upgrade to cancer for breast lesions with uncertain malignant potential (B3 lesions) diagnosed at needle biopsy is highly influenced by several factors, but large series are seldom available. We retrospectively assessed the upgrade rates of a consecutive series of B3 lesions diagnosed at ultrasound- or mammography-guided vacuum-assisted biopsy (VAB) at an EUSOMA-certified Breast Unit over a 7-year timeframe. The upgrade rate was defined as the number of ductal carcinoma in situ (DCIS) or invasive cancer at pathology after excision or during follow-up divided by the total number of B3 lesions. All lesions were reviewed by one of four pathologists with a second opinion for discordant assessments of borderline cases. Excision or surveillance were defined by the multidisciplinary tumor board, with 6- and 12-month follow-up. Out of 3634 VABs (63% ultrasound-guided), 604 (17%) yielded a B3 lesion. After excision, 17/604 B3 lesions were finally upgraded to malignancy (2.8%, 95% confidence interval [CI] 1.8–4.5%), 10/17 (59%) being upgraded to DCIS and 7/17 (41%) to invasive carcinoma. No cases were upgraded during follow-up. B3a lesions showed a significantly lower upgrade rate (0.4%, 95% CI 0.1–2.1%) than B3b lesions (4.7%, 95% CI 2.9–7.5%, p = 0.001), that had a 22.0 adjusted odds ratio for upgrade (95% CI 2.1–232.3). No significant difference was found in upgrade rates according to imaging guidance or needle caliper. Surveillance-oriented management can be considered for B3a lesions, while surgical excision should be pursued for B3b lesions. [ABSTRACT FROM AUTHOR]

Introduction: Rifampicin is one of the most effective antibiotics for treating tuberculosis, but it has been associated with adverse reactions, such as nephrotoxicity, sometimes resulting in acute renal failure with oligoanuria, and hepatotoxicity. Although deterioration of renal function, determined by acute tubulointerstitial nephritis and/or acute tubular necrosis, typically appears in patients receiving intermittent rifampicin therapy, some authors have also reported cases occurring during continuous rifampicin therapy.Case Presentation: We describe the case of acute renal failure with polyuria occurring in a previously healthy 50-year-old Caucasian man undergoing continuous therapy with rifampicin for culture-confirmed pulmonary tuberculosis. The patient was admitted to the L. Spallanzani National Institute for Infectious Diseases, Rome, Italy, with a 1-month history of coughing, fever and weight loss. After 6 weeks of standard antituberculous treatment, progressive deterioration of his renal function was observed: creatinine levels rose from 38.9μmol/L to 318.2μmol/L and urine volume also progressively increased to reach a state of true polyuria (8 to 10L of urine per day). He was diagnosed with suspected acute rifampicin-induced renal failure. A renal biopsy showed focal segmental glomerulosclerosis associated with acute tubulointerstitial nephritis. Rifampicin was discontinued with excellent results: after 15 days his renal function began to improve and his serum creatinine values returned to normal.Conclusion: A high index of suspicion for rifampicin-associated acute renal failure should be maintained in patients with pulmonary tuberculosis who develop progressive deterioration of renal function during treatment with rifampicin. Early diagnosis and discontinuation of rifampicin are of fundamental importance for recovering renal function. [ABSTRACT FROM AUTHOR]

Abstract: Cross-linked polyethylene (XLPE) films have been coated with nanostructured hybrid organic–inorganic coatings in order to improve their durability. For this purpose, bi- and mono-layer coatings containing different amount of silica and different organic polymers have been prepared through sol-gel reactions and applied to XLPE commercial films. The thermo-oxidative stability, electrical strength and conductivity of XLPE coated films have been investigated after ageing in air at temperatures above the on-service conditions, i.e. at 105 and 120 °C for 1900 and 600 h, respectively. The performed investigations (FT-IR, DSC, TGA and electrical properties) showed that all the coatings tested were able to strongly protect XLPE against oxidation, and that the coating with a PVOH/SiO2 layer gave the best protection. The increase of thermal resistance induced by the coatings reflects on the electrical strength after ageing, which is higher for coated samples than for uncoated ones. Moreover, while ageing has only a slight effect on electrical conductivity in different coated samples, a strong increase of conductivity was observed after ageing for highly oxidated uncoated samples. [Copyright &y& Elsevier]

To examine whether specific T-cell-responses to SARS-CoV-2 peptides can be detected in COVID-19 using a whole-blood experimental setting, which may be further explored as a potential diagnostic tool. We evaluated interferon (IFN)-γ levels after stimulating whole-blood with spike and remainder-antigens peptides megapools (MP) derived from SARS-CoV-2 sequences; interleukin (IL)-1β, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17A, eotaxin, basic fibroblast growth factor (FGF), granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), IFN-γ, Interferon gamma-induced protein 10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1α, MIP-1β, Platelet-derived growth factor (PDGF), RANTES (regulated on activation, normal T cell expressed and secreted), tumour necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF) were also evaluated. IFN-γ-response to spike and remainder-antigens MPs was significantly increased in 35 COVID-19 patients compared with 29 'no COVID-19' individuals (medians spike-MP: 0.26 vs 0, p = 0.0002; medians remainder-antigens-MP: 0.07 vs 0.02; p = 0.02). This response was detected independently of patients' clinical parameters. IFN-γ-response to SARS-CoV-2-unrelated antigens cytomegalovirus (CMV) and Staphylococcal Enterotoxin B (SEB) was similar in COVID-19 compared with 'no COVID-19' individuals (median CMV: 3.46 vs 5.28, p = 0.16; median SEB: 12.68 vs 15.05; p = 0.1). In response to spike-MPs in COVID-19- compared with 'no COVID-19' -individuals, we found significant higher median of IL-2 (50.08 vs 0, p = 0.0018), IFN-γ (90.16 vs 0, p = 0.01), IL-4 (0.52 vs 0, p = 0.03), IL-13 (0.84 vs 0, p = 0.007) and MCP-1 (4602 vs 359.2, p = 0.05). Immune response to SARS-CoV-2 peptides in a whole-blood assay is associated with COVID-19 and it is characterized by both Th1 and Th2 profile. This experimental approach may be useful for developing new T-cell based diagnostic tests for disease and vaccine settings. Image 1 [ABSTRACT FROM AUTHOR]

Background: Multidrug-resistant tuberculosis (MDR-TB) requires lengthy use of second-line drugs, burdened by many side effects. Hepatitis C virus (HCV) chronic infection increases risk of drug-induced liver injury (DILI) in these patients. Data on MDR-TB patients with concurrent HCV chronic infection treated at the same time with second-line antitubercular drugs and new direct-acting antivirals (DAAs) are lacking. We evaluate if treating at the same time HCV infection and pulmonary MDR-TB is feasible and effective.Cases Presentation: In this study, we described two cases of patients with pulmonary MDR-TB and concurrent HCV chronic infection cured with DAAs at a Tertiary Infectious Diseases Hospital in Italy. During antitubercular treatment, both patients experienced a DILI before treating HCV infection. After DAAs liver enzymes normalized and HCV RNA was undetectable. Then antitubercular regimen was started according to the institutional protocol, drawn up following WHO MDR-TB guidelines. It was completed without further liver side effects and patients were declared cured from both HCV infection and MDR-TB.Conclusions: We suggest to consider treatment of chronic hepatitis C with DAAs as a useful intervention for reintroduction of second-line antitubercular agents in those patients who developed DILI, reducing the risk of treatment interruption when re-exposed to these drugs. [ABSTRACT FROM AUTHOR]

Describes cases of Aspergillus endocarditis in injection drug users (IDU). Risk factors associated with the acquisition of invasive aspergillosis; Percentage of infections in IDU attributed to fungal infections; Association of Aspergillus endocarditis with HIV infection.

Lack of biomarkers for treatment monitoring is listed among the main requirements for next generation assays, as identified globally among tuberculosis (TB) researchers. In this study, we evaluated in a low TB endemic country such as Italy, the effect of preventive therapy on the results obtained in the QuantiFERON TB Plus (QFT-Plus), in a cohort of subjects with latent TB infection (LTBI) and active TB. We found that TB therapy significantly decreased IFN-γ values and number of responders to TB1- and TB2- peptides stimulation in both LTBI and active TB patients. Stratifying LTBI subjects according to the type of preventive TB therapy used, we found that INH treatment but not INH and RIF significantly decreased IFN-γ production. Stratifying the active TB patients according the microbiological status, we found that TB therapy significantly decreased IFN-γ response to antigen present in QFT-Plus test in patients with clinical diagnosis compared to those with a microbiological diagnosis. In conclusions, we demonstrated that TB therapy decreases IFN-γ level in response to antigen present in QFT-Plus test in LTBI and active TB patients. Future studies are needed to better characterize Mtb-specifc response as a potential marker for monitoring TB therapy and preventive treatment effects. [ABSTRACT FROM AUTHOR]