Imaging Severity COVID-19 Assessment in Vaccinated and Unvaccinated Patients: Comparison of the Different Variants in a High Volume Italian Reference Center.

Purpose: To analyze the vaccine effect by comparing five groups: unvaccinated patients with Alpha variant, unvaccinated patients with Delta variant, vaccinated patients with Delta variant, unvaccinated patients with Omicron variant, and vaccinated patients with Omicron variant, assessing the "gravity" of COVID-19 pulmonary involvement, based on CT findings in critically ill patients admitted to Intensive Care Unit (ICU). Methods: Patients were selected by ICU database considering the period from December 2021 to 23 March 2022, according to the following inclusion criteria: patients with proven Omicron variant COVID-19 infection with known COVID-19 vaccination with at least two doses and with chest Computed Tomography (CT) study during ICU hospitalization. Wee also evaluated the ICU database considering the period from March 2020 to December 2021, to select unvaccinated consecutive patients with Alpha variant, subjected to CT study, consecutive unvaccinated and vaccinated patients with Delta variant, subjected to CT study, and, consecutive unvaccinated patients with Omicron variant, subjected to CT study. CT images were evaluated qualitatively using a severity score scale of 5 levels (none involvement, mild: ≤25% of involvement, moderate: 26−50% of involvement, severe: 51−75% of involvement, and critical involvement: 76−100%) and quantitatively, using the Philips IntelliSpace Portal clinical application CT COPD computer tool. For each patient the lung volumetry was performed identifying the percentage value of aerated residual lung volume. Non-parametric tests for continuous and categorical variables were performed to assess statistically significant differences among groups. Results: The patient study group was composed of 13 vaccinated patients affected by the Omicron variant (Omicron V). As control groups we identified: 20 unvaccinated patients with Alpha variant (Alpha NV); 20 unvaccinated patients with Delta variant (Delta NV); 18 vaccinated patients with Delta variant (Delta V); and 20 unvaccinated patients affected by the Omicron variant (Omicron NV). No differences between the groups under examination were found (p value > 0.05 at Chi square test) in terms of risk factors (age, cardiovascular diseases, diabetes, immunosuppression, chronic kidney, cardiac, pulmonary, neurologic, and liver disease, etc.). A different median value of aerated residual lung volume was observed in the Delta variant groups: median value of aerated residual lung volume was 46.70% in unvaccinated patients compared to 67.10% in vaccinated patients. In addition, in patients with Delta variant every other extracted volume by automatic tool showed a statistically significant difference between vaccinated and unvaccinated group. Statistically significant differences were observed for each extracted volume by automatic tool between unvaccinated patients affected by Alpha variant and vaccinated patients affected by Delta variant of COVID-19. Good statistically significant correlations among volumes extracted by automatic tool for each lung lobe and overall radiological severity score were obtained (ICC range 0.71−0.86). GGO was the main sign of COVID-19 lesions on CT images found in 87 of the 91 (95.6%) patients. No statistically significant differences were observed in CT findings (ground glass opacities (GGO), consolidation or crazy paving sign) among patient groups. Conclusion: In our study, we showed that in critically ill patients no difference were observed in terms of severity of disease or exitus, between unvaccinated and vaccinated patients. The only statistically significant differences were observed, with regard to the severity of COVID-19 pulmonary parenchymal involvement, between unvaccinated patients affected by Alpha variant and vaccinated patients affected by Delta variant, and between unvaccinated patients with Delta variant and vaccinated patients with Delta variant.

Quantitative Analysis of Residual COVID-19 Lung CT Features: Consistency among Two Commercial Software.

OBJECTIVE: To investigate two commercial software and their efficacy in the assessment of chest CT sequelae in patients affected by COVID-19 pneumonia, comparing the consistency of tools. MATERIALS AND METHODS: Included in the study group were 120 COVID-19 patients (56 women and 104 men; 61 years of median age; range: 21-93 years) who underwent chest CT examinations at discharge between 5 March 2020 and 15 March 2021 and again at a follow-up time (3 months; range 30-237 days). A qualitative assessment by expert radiologists in the infectious disease field (experience of at least 5 years) was performed, and a quantitative evaluation using thoracic VCAR software (GE Healthcare, Chicago, Illinois, United States) and a pneumonia module of ANKE ASG-340 CT workstation (HTS Med & Anke, Naples, Italy) was performed. The qualitative evaluation included the presence of ground glass opacities (GGOs) consolidation, interlobular septal thickening, fibrotic-like changes (reticular pattern and/or honeycombing), bronchiectasis, air bronchogram, bronchial wall thickening, pulmonary nodules surrounded by GGOs, pleural and pericardial effusion, lymphadenopathy, and emphysema. A quantitative evaluation included the measurements of GGOs, consolidations, emphysema, residual healthy parenchyma, and total lung volumes for the right and left lung. A chi-square test and non-parametric test were utilized to verify the differences between groups. Correlation coefficients were used to analyze the correlation and variability among quantitative measurements by different computer tools. A receiver operating characteristic (ROC) analysis was performed. RESULTS: The correlation coefficients showed great variability among the quantitative measurements by different tools when calculated on baseline CT scans and considering all patients. Instead, a good correlation (≥0.6) was obtained for the quantitative GGO, as well as the consolidation volumes obtained by two tools when calculated on baseline CT scans, considering the control group. An excellent correlation (≥0.75) was obtained for the quantitative residual healthy lung parenchyma volume, GGO, consolidation volumes obtained by two tools when calculated on follow-up CT scans, and for residual healthy lung parenchyma and GGO quantification when the percentage change of these volumes were calculated between a baseline and follow-up scan. The highest value of accuracy to identify patients with RT-PCR positive compared to the control group was obtained by a GGO total volume quantification by thoracic VCAR (accuracy = 0.75). CONCLUSIONS: Computer aided quantification could be an easy and feasible way to assess chest CT sequelae due to COVID-19 pneumonia; however, a great variability among measurements provided by different tools should be considered.

Management of Spontaneous Bleeding in COVID-19 Inpatients: Is Embolization Always Needed?

BACKGROUND: critically ill patients with SARS-CoV-2 infection present a hypercoagulable condition. Anticoagulant therapy is currently recommended to reduce thrombotic risk, leading to potentially severe complications like spontaneous bleeding (SB). Percutaneous transcatheter arterial embolization (PTAE) can be life-saving in critical patients, in addition to medical therapy. We report a major COVID-19 Italian Research Hospital experience during the pandemic, with particular focus on indications and technique of embolization. METHODS: We retrospectively included all subjects with SB and with a microbiologically confirmed SARS-CoV-2 infection, over one year of pandemic, selecting two different groups: (a) patients treated with PTAE and medical therapy; (b) patients treated only with medical therapy. Computed tomography (CT) scan findings, clinical conditions, and biological findings were collected. RESULTS: 21/1075 patients presented soft tissue SB with an incidence of 1.95%. 10/21 patients were treated with PTAE and medical therapy with a 30-days survival of 70%. Arterial blush, contrast late enhancement, and dimensions at CT scan were found discriminating for the embolization (p < 0.05). CONCLUSIONS: PTAE is an important tool in severely ill, bleeding COVID-19 patients. The decision for PTAE of COVID-19 patients must be carefully weighted with particular attention paid to the clinical and biological condition, hematoma location and volume.

An explainable AI system for automated COVID-19 assessment and lesion categorization from CT-scans.

COVID-19 infection caused by SARS-CoV-2 pathogen has been a catastrophic pandemic outbreak all over the world, with exponential increasing of confirmed cases and, unfortunately, deaths. In this work we propose an AI-powered pipeline, based on the deep-learning paradigm, for automated COVID-19 detection and lesion categorization from CT scans. We first propose a new segmentation module aimed at automatically identifying lung parenchyma and lobes. Next, we combine the segmentation network with classification networks for COVID-19 identification and lesion categorization. We compare the model's classification results with those obtained by three expert radiologists on a dataset of 166 CT scans. Results showed a sensitivity of 90.3% and a specificity of 93.5% for COVID-19 detection, at least on par with those yielded by the expert radiologists, and an average lesion categorization accuracy of about 84%. Moreover, a significant role is played by prior lung and lobe segmentation, that allowed us to enhance classification performance by over 6 percent points. The interpretation of the trained AI models reveals that the most significant areas for supporting the decision on COVID-19 identification are consistent with the lesions clinically associated to the virus, i.e., crazy paving, consolidation and ground glass. This means that the artificial models are able to discriminate a positive patient from a negative one (both controls and patients with interstitial pneumonia tested negative to COVID) by evaluating the presence of those lesions into CT scans. Finally, the AI models are integrated into a user-friendly GUI to support AI explainability for radiologists, which is publicly available at http://perceivelab.com/covid-ai. The whole AI system is unique since, to the best of our knowledge, it is the first AI-based software, publicly available, that attempts to explain to radiologists what information is used by AI methods for making decisions and that proactively involves them in the decision loop to further improve the COVID-19 understanding.

Prophylactic heparin and risk of orotracheal intubation or death in patients with mild or moderate COVID-19 pneumonia.

Prophylactic low molecular weight heparin (pLMWH) is currently recommended in COVID-19 to reduce the risk of coagulopathy. The aim of this study was to evaluate whether the antinflammatory effects of pLMWH could translate in lower rate of clinical progression in patients with COVID-19 pneumonia. Patients admitted to a COVID-hospital in Rome with SARS-CoV-2 infection and mild/moderate pneumonia were retrospectively evaluated. The primary endpoint was the time from hospital admission to orotracheal intubation/death (OTI/death). A total of 449 patients were included: 39% female, median age 63 (IQR, 50-77) years. The estimated probability of OTI/death for patients receiving pLMWH was: 9.5% (95% CI 3.2-26.4) by day 20 in those not receiving pLMWH vs. 10.4% (6.7-15.9) in those exposed to pLMWH; p-value = 0.144. This risk associated with the use of pLMWH appeared to vary by PaO2/FiO2 ratio: aHR 1.40 (95% CI 0.51-3.79) for patients with an admission PaO2/FiO2 ≤ 300 mmHg and 0.27 (0.03-2.18) for those with PaO2/FiO2 > 300 mmHg; p-value at interaction test 0.16. pLMWH does not seem to reduce the risk of OTI/death mild/moderate COVID-19 pneumonia, especially when respiratory function had already significantly deteriorated. Data from clinical trials comparing the effect of prophylactic vs. therapeutic dosage of LMWH at various stages of COVID-19 disease are needed.

Role of testosterone in SARS-CoV-2 infection: A key pathogenic factor and a biomarker for severe pneumonia.

OBJECTIVES: 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. DESIGN AND METHODS: 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 PaO2/FiO2 <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 PaO2/FiO2 >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. RESULTS: 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. CONCLUSIONS: A low level of testosterone was found to be a marker of clinical severity of COVID-19.

COVID-19 in people living with HIV: Clinical implications of dynamics of the immune response to SARS-CoV-2.

Little evidence on coronavirus disease 2019 (COVID-19) in people living with HIV (PLWH) is currently available. We reported clinical and viroimmunological data of all HIV-positive patients admitted to our center with COVID-19 from March 1 to May 12, 2020. Overall, five patients were included: all were virologically-suppressed on antiretroviral therapy and CD4+ count was greater than 350 cell/mm3 in all but two patients. Although all patients had evidence of pneumonia on admission, only one developed respiratory failure. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was never detected from nasopharyngeal swabs in two patients, whereas in the others, viral clearance occurred within a maximum of 43 days. Immunoglobulin G production was elicited in all patients and neutralizing antibodies in all but one patient. Specific-T-cell response developed in all patients but was stronger in those with the more severe presentations. Similarly, the highest level of proinflammatory cytokines was found in the only patient experiencing respiratory failure. Despite a mild presentation, patients with more pronounced immunosuppression showed high degrees of both cytokines production and immune activation. Our study did not find an increased risk and severity of COVID-19 in PLWH. Adaptative cellular immune response to SARS-CoV-2 appeared to correlate to disease severity. The mild clinical picture showed in advanced HIV patients, despite a significant T-cell activation and inflammatory profile, suggests a potential role of HIV-driven immunological dysregulation in avoiding immune-pathogenetic processes. However, other possible explanations, as a protective role of certain antiretroviral drugs, should be considered. Further larger studies are needed to better clarify the impact of HIV infection on COVID-19.

Association of Sarcopenia and Body Composition With Short-term Outcomes After Liver Resection for Malignant Tumors.

Importance: Previous retrospective studies have shown that sarcopenia substantially alters the postoperative and oncological outcomes after liver resection for malignant tumors. However, the evidence is limited to small retrospective studies with heterogeneous results and the lack of standardized measurements of sarcopenia. Objective: To investigate the role of sarcopenia as a risk factor associated with 90-day morbidity after liver resection for malignant tumors. Design, Setting, and Participants: This cohort study included 234 consecutive patients undergoing liver resection for malignant tumors at San Camillo Forlanini Hospital, Rome, Italy, between June 1, 2018, and December 15, 2019. Muscle mass and strength were assessed using the skeletal muscle index (SMI) on preoperative computed tomographic scans and the handgrip strength test, respectively. Patients were then divided into the following 4 groups: group A (normal muscle mass and strength), group B (reduced muscle strength), group C (reduced muscle mass), and group D (reduced muscle mass and strength). Main Outcomes and Measures: The primary outcome of the study was 90-day morbidity. The following secondary outcomes were investigated: 90-day mortality, hospital stay, and readmission rate. Results: Sixty-four major and 170 minor hepatectomies were performed in 234 patients (median age, 66.50 [interquartile range, 58.00-74.25] years; 158 men [67.5%]). The median SMI of the entire population was 46.22 (interquartile range, 38.60-58.20) cm/m2. The median handgrip strength was 30.80 (interquartile range, 22.30-36.90) kg. Patients in group D had a statistically significantly higher rate of 90-day morbidity than patients in the other groups (51.5% [35 of 68] vs 38.7% [29 of 75] in group C, 23.1% [3 of 13] in group B, and 6.4% [5 of 78] in group A; P < .001). Compared with patients in the other groups, those in group D had a longer hospital stay (10 days vs 8 days in group C, 9 days in group B, and 6 days in group A; P < .001), and more patients in this group were readmitted to the hospital (8.8% [6 of 68] vs 5.3% [4 of 75] in group C, 7.7% [1 of 13] in group B, and 0% [0 of 78] in group A; P = .02). Sarcopenia, portal hypertension, liver cirrhosis, and biliary reconstruction were independent risk factors associated with 90-day morbidity. Conclusions and Relevance: Sarcopenia appears to be associated with adverse outcomes after liver resection for malignant tumors. Both muscle mass measurements on computed tomographic scans and muscle strength assessments with the handgrip strength test should be performed at the first clinical encounter to better classify patients and to minimize the risk of morbidity.

Active Pulmonary Tuberculosis in Elderly Patients: A 2016-2019 Retrospective Analysis from an Italian Referral Hospital.

Tuberculosis (TB) in the elderly (>65 years old) has increasingly become a global health problem. It has long been recognized that older people are vulnerable to developing tuberculosis. We retrospectively evaluated data from patients older than 65 years diagnosed with pulmonary TB admitted to the National Institute for Infectious Diseases L. Spallanzani, Rome, Italy, from 1 January 2016 to 31 December 2019. One hundred and six consecutive patients were diagnosed with pulmonary TB and 68% reported at least one comorbidity and 44% at least one of the TB risk-factors. Out of the 26 elderly patients who reported an adverse event, having risk factors for TB (O.R. (Odds Ratios) = 1.45; 95% CI 1.12-3.65) and the presence of cavities on Chest X-rays (O.R. = 1.42; 95% CI 1.08-2.73) resulted in being more likely to be associated with adverse events in elderly patients. Having weight loss (O.R. = 1.31; 95% CI 1.08-1.55) and dyspnea (O.R. = 1.23; 95% CI 1.13-1.41) resulted in being significant predictors of unsuccessful treatment outcome in elderly patients. Older people with TB represent a vulnerable group, with high mortality rate, with a challenging diagnosis. Hospitalizations in tertiary referral hospital with clinical expertise in TB management can be useful to improve the outcome of these fragile patients.

Development of a clinical decision support system for severity risk prediction and triage of COVID-19 patients at hospital admission: an international multicentre study.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has globally strained medical resources and caused significant mortality. OBJECTIVE: To develop and validate a machine-learning model based on clinical features for severity risk assessment and triage for COVID-19 patients at hospital admission. METHOD: 725 patients were used to train and validate the model. This included a retrospective cohort from Wuhan, China of 299 hospitalised COVID-19 patients from 23 December 2019 to 13 February 2020, and five cohorts with 426 patients from eight centres in China, Italy and Belgium from 20 February 2020 to 21 March 2020. The main outcome was the onset of severe or critical illness during hospitalisation. Model performances were quantified using the area under the receiver operating characteristic curve (AUC) and metrics derived from the confusion matrix. RESULTS: In the retrospective cohort, the median age was 50 years and 137 (45.8%) were male. In the five test cohorts, the median age was 62 years and 236 (55.4%) were male. The model was prospectively validated on five cohorts yielding AUCs ranging from 0.84 to 0.93, with accuracies ranging from 74.4% to 87.5%, sensitivities ranging from 75.0% to 96.9%, and specificities ranging from 55.0% to 88.0%, most of which performed better than the pneumonia severity index. The cut-off values of the low-, medium- and high-risk probabilities were 0.21 and 0.80. The online calculators can be found at www.covid19risk.ai. CONCLUSION: The machine-learning model, nomogram and online calculator might be useful to access the onset of severe and critical illness among COVID-19 patients and triage at hospital admission.

Patient Access to an Online Portal for Outpatient Radiological Images and Reports: Two Years' Experience.

To assess the incidence of outpatient examinations delivered through a web portal in the Latium Region in 2 years and compare socio-demographic characteristics of these users compared to the total of examinations performed. All radiological exams (including MRI, X-ray and CT) performed from March 2017 to February 2019 were retrospectively analysed. For each exam, anonymized data of users who attended the exam were extracted and their characteristics were compared according to digital access to the reports. Overall, 9068 exams were performed in 6720 patients (55.8% males, median age 58 years, interquartile range (IQR) 46-70) of which 90.2% residents in Rome province, mainly attending a single radiological examination (77.3%). Among all exams, 446 (4.9%) were accessed, of which 190 (4.4%) in the first and 5.4% in the second year (p < 0.041). MRI was the type of exams mostly accessed (175, 7.0%). Being resident in the provinces of the Latium Region other than Rome was associated with a higher access rate (OR = 1.84, p = 0.001). Considering the overall costs sustained to implement a web portal which allows users a personal access to their own reports, if all users would have accessed/downloaded their exams, an overall users' and hospital savings up to €255,808.28 could have been determined. The use of a web portal could represent a consistent economical advantage for the user, the hospital and the environment. Even if increasing over time, the use of web portal is still limited and strategies to increase the use of such systems should be implemented.

2019-novel Coronavirus severe adult respiratory distress syndrome in two cases in Italy: An uncommon radiological presentation.

INTRODUCTION: Several recent case reports have described common early chest imaging findings of lung pathology caused by 2019 novel Coronavirus (SARS-COV2) which appear to be similar to those seen previously in SARS-CoV and MERS-CoV infected patients. OBJECTIVE: We present some remarkable imaging findings of the first two patients identified in Italy with COVID-19 infection travelling from Wuhan, China. The follow-up with chest X-Rays and CT scans was also included, showing a progressive adult respiratory distress syndrome (ARDS). RESULTS: Moderate to severe progression of the lung infiltrates, with increasing percentage of high-density infiltrates sustained by a bilateral and multi-segmental extension of lung opacities, were seen. During the follow-up, apart from pleural effusions, a tubular and enlarged appearance of pulmonary vessels with a sudden caliber reduction was seen, mainly found in the dichotomic tracts, where the center of a new insurgent pulmonary lesion was seen. It could be an early alert radiological sign to predict initial lung deterioration. Another uncommon element was the presence of mediastinal lymphadenopathy with short-axis oval nodes. CONCLUSIONS: Although only two patients have been studied, these findings are consistent with the radiological pattern described in literature. Finally, the pulmonary vessels enlargement in areas where new lung infiltrates develop in the follow-up CT scan, could describe an early predictor radiological sign of lung impairment.

Image quality and radiation dose reduction in chest CT in pulmonary infection.

PURPOSE: To evaluate the effect of dose reduction with iterative reconstruction (IR) on image quality of chest CT scan comparing two protocols. MATERIALS AND METHODS: Fifty-nine patients were enrolled. The two CT protocols were applied using Iterative Reconstruction (ASIR™) 40% but different noise indexes, recording dose-length product (DLP) and volume computed tomography dose index (CTDIvol). The subjective IQ was rated based on the distinction of anatomic details using a 4-point Likert scale based on the European Guidelines on Quality Criteria for CT. For each patient, two single CTs, at enrollment (group 1) and at follow-up after lowering the dose (group 2), were evaluated by two radiologists evaluating, for each examination, five different lung regions (central zone-CZ; peripheral zone-PZ; sub-pleural region-SPR; centrilobular region-CLR; and apical zone-AZ). An inter-observer agreement was expressed by weighted Cohen's kappa statistics (k) and intra-individual differences of subjective image analysis through visual grading characteristic (VGC) analysis. RESULTS: An average 50.4% reduction in CTDIvol and 51.5% reduction in DLP delivered were observed using the dose-reduced protocol. An agreement between observers evaluating group 1 CTs was perfect (100%) and moderate to good in group 2 examinations (k-Cohen ranging from 0.56 for PZ and AZ to 0.70 for SPR). In the VGC analysis, image quality ratings were significantly better for group 1 than group 2 scans for all regions (AUCVGC ranging from 0.56 for CZ to 0.62). However, disagreement was limited to a score 4 (excellent)-to-score 3 (good) IQ transition; apart from a single case in PZ, both the observers scored the IQ at follow-up as 2 (sufficient) starting from a score 4 (excellent). CONCLUSION: Dose reduction achieved in the follow-up CT scans, although a lower IQ still allows a good diagnostic confidence.

Central Nervous System involvement in tuberculosis: An MRI study considering differences between patients with and without Human Immunodeficiency Virus 1 infection.

BACKGROUND: Magnetic resonance imaging (MRI) is largely used in the diagnosis of central nervous system involvement of tuberculosis (CNSTB), yet there is no MRI comparison study between HIV+ and HIV- patients with CNSTB. The aim of the present study was to identify MRI differences in CNSTB between HIV+ and HIV- patients and possibly find early characteristics that could raise the suspect of this disease. METHODS: We included all patients admitted in our institution between 2011 and 2018 with confirmed diagnosis of CNSTB, and MRI performed in the first week. Patients with preexisting brain pathology or immunodeficiency not HIV related were excluded. We compared CNSTB MRI features between the two groups. RESULTS: Sixty-nine patients were included (19 HIV+; 50 HIV-). Findings in HIV+ group: 6 lung TB, 5 hydrocephalus, 4 meningeal enhancement, 6 stroke, 2 hemorrhages, and 10 tuberculomas. HIV- group: 22 lung tuberculosis, 15 hydrocephalus, 21 meningeal enhancement, 5 stroke, 4 hemorrhages, 20 tuberculomas. The only statistically significant difference between the two groups was in the stroke occurrence, more frequent in the HIV+ group (P=.028), all involving the basal ganglia. CONCLUSIONS: Stroke involving the basal ganglia best differentiates CNSTB patients who are HIV+ from those HIV-. This finding was not correlated with meningeal enhancement suggesting that small arteries involvement might precede it. Therefore, we think that HIV+ patients with a new onset of stroke should be evaluated for CNSTB. Follow-up MRI should also be planned since meningeal enhancement might appear in later stages of the disease.

Effect of therapy on Quantiferon-Plus response in patients with active and latent tuberculosis 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.

Pulmonary measles disease: old and new imaging tools.

BACKGROUND: Measles virus can cause lower respiratory tract infection, so that chest radiography is necessary to investigate lung involvement in patients with respiratory distress. PURPOSE: To assess measles pneumonia imaging during the measles outbreak occurred in 2016-2017 in Italy. MATERIAL AND METHODS: We retrospectively observed adult patients with a serological diagnosis of measles, who underwent chest-X rays for suspected pneumonia. If a normal radiography resulted, the patient underwent unenhanced CT. A CT post processing software package was used for an additional quantitative lung and airway involvement analysis . RESULTS: Among 290 patients affected by measles, 150 underwent chest-X ray. Traditional imaging allowed the pneumonia diagnosis in 114 patients (76%). The most frequent abnormality at chest X-rays was bronchial wall thickening, observed in 88.5% of the cases; radiological findings are faint in the 25% of the cases (29/114 patients). In nine subjects with a normal chest X-ray, unenhanced CT with a quantitative analysis was performed, and depicted features consistent with constrictive bronchiolitis. CONCLUSION: Measles may produce bronchiolitis and pneumonia. In the cases in which involvement of pulmonary parenchyma is not sufficient to result in radiological abnormalities, CT used with a dedicated postprocessing software package, provides an accurate lungs and airways analysis, also determining the percentage of lung involvement.

Evaluation of IP-10 in Quantiferon-Plus as biomarker for the diagnosis of latent tuberculosis infection.

The QuantiFERON-TB Gold Plus (QFT-Plus) is a new test for latent tuberculosis infection (LTBI) diagnosis, in which has been added a new tube containing shorter peptides stimulating CD8 T-cells and CD4-stimulating-peptides. Measurement of alternative biomarkers to Interferon-γ (IFN-γ) in QFT-Plus may improve its sensitivity. Interferon-γ inducible protein 10 (IP-10), has been proposed as a tuberculosis (TB) biomarker. We aimed to evaluate the IP-10 accuracy in QFT-Plus for LTBI diagnosis. QFT-Plus was performed in 36 active TB, 31 LTBI and 16 healthy donors (HD). IP-10 was detected by ELISA. IP-10 is increased in TB1 and TB2 tubes in subjects with active TB and LTBI compared to HD. A ROC analysis comparing active TB and HD was performed and a cut-off of 1174 pg/mL for TB1 and 928.8 pg/mL for TB2 identified active TB with 86% sensitivity (Se) and 94% specificity (Sp). Moreover, increased IP-10 in response to TB1 was found in subjects with LTBI compared to those with active TB. A cut-off point of ≥16,108 pg/mL was chosen to maximize the test performance. However, the test predicted LTBI only with 58% Se and 61% Sp. These results suggest that IP-10 is an alternative biomarker to IFN-γ in the QFT-Plus format.

Polyfunctional Specific Response to Echinococcus Granulosus Associates to the Biological Activity of the Cysts.

BACKGROUND: Cystic echinococcosis (CE) is a complex disease caused by Echinococcus granulosus (E.granulosus), and its immunophatogenesis is still not clearly defined. A peculiar feature of chronic CE is the coexistence of Th1 and Th2 responses. It has been suggested that Th1 cytokines are related to disease resistance, whereas Th2 cytokines are related to disease susceptibility and chronicity. The aim of this study was to evaluate, by multi-parametric flow cytometry (FACS), the presence of CE specific immune signatures. METHODOLOGY/PRINCIPAL FINDINGS: We enrolled 54 subjects with suspected CE; 42 of them had a confirmed diagnosis, whereas 12 were classified as NO-CE. Based on the ultrasonography images, CE patients were further categorized as being in "active stages" (25) and "inactive stages" (17). The ability of CD4+ T-cells to produce IFN-γ, IL-2, TNF-α, Th2 cytokines or IL-10 was assessed by FACS on antigen-specific T-cells after overnight stimulation with Antigen B (AgB) of E.granulosus. Cytokine profiles were evaluated in all the enrolled subjects. The results show that none of the NO-CE subjects had a detectable AgB-specific response. Among the CE patients, the frequency and proportions of AgB-specific CD4+ T-cells producing IL-2+TNF-α+Th2+ or TNF-α+Th2+ were significantly increased in the "active stages" group compared to the "inactive stages" group. Moreover, an increased proportion of the total polyfunctional subsets, as triple-and double-functional CD4 T-cells, was found in CE patients with active disease. The response to the mitogen, used as a control stimulus to evaluate the immune competence status, was characterized by the same cytokine subsets in all the subjects enrolled, independent of CE. CONCLUSIONS: We demonstrate, for the first time to our knowledge, that polyfunctional T-cell subsets as IL-2+TNF-α+Th2+ triple-positive and TNF-α+Th2+ double-positive specific T-cells associate with cyst biological activity. These results contribute to increase knowledge of CE immunophatogenesis and the disease outcome in terms of control and persistence.

Radiographic imaging in Ebola Virus Disease: protocol to acquire chest radiographs.

UNLABELLED: Proper procedures to minimize the risk of contamination in contagious and potentially lethal viral infections are needed; therefore radiology departments should develop appropriate imaging protocols. We describe the imaging protocol used by National Institute for Infectious Diseases Lazzaro Spallanzani to acquire chest radiographs in patients with Ebola virus disease. KEY POINTS: • Nosocomial transmission to healthcare workers can be prevented using protective equipment. • Chest radiographs can be required in Ebola Virus Disease. • The protocol for performing chest radiographs on patients with Ebola is described.