Timing and Outcomes of Noninvasive Ventilation in 307 ARDS COVID-19 Patients: An Observational Study in an Italian Third Level COVID-19 Hospital.

Background and Objectives: Background: Coronavirus disease 2019 (COVID-19) is a novel cause of Acute Respiratory Distress Syndrome (ARDS). Noninvasive ventilation (NIV) is widely used in patients with ARDS across several etiologies. Indeed, with the increase of ARDS cases due to the COVID-19 pandemic, its use has grown significantly in hospital wards. However, there is a lack of evidence to support the efficacy of NIV in patients with COVID-19 ARDS. Materials and Methods: We conducted an observational cohort study including adult ARDS COVID-19 patients admitted in a third level COVID-center in Rome, Italy. The study analyzed the rate of NIV failure defined by the occurrence of orotracheal intubation and/or death within 28 days from starting NIV, its effectiveness, and the associated relative risk of death. The factors associated with the outcomes were identified through logistic regression analysis. Results: During the study period, a total of 942 COVID-19 patients were admitted to our hospital, of which 307 (32.5%) presented with ARDS at hospitalization. During hospitalization 224 (23.8%) were treated with NIV. NIV failure occurred in 84 (37.5%) patients. At 28 days from starting NIV, moderate and severe ARDS had five-fold and twenty-fold independent increased risk of NIV failure (adjusted odds ratio, aOR = 5.01, 95% CI 2.08−12.09, and 19.95, 95% CI 5.31−74.94), respectively, compared to patients with mild ARDS. A total of 128 patients (13.5%) were admitted to the Intensive Care Unit (ICU). At 28-day from ICU admission, intubated COVID-19 patients treated with early NIV had 40% lower mortality (aOR 0.60, 95% CI 0.25−1.46, p = 0.010) compared with patients that underwent orotracheal intubation without prior NIV. Conclusions: These findings show that NIV failure was independently correlated with the severity category of COVID-19 ARDS. The start of NIV in COVID-19 patients with mild ARDS (P/F > 200 mmHg) appears to increase NIV effectiveness and reduce the risk of orotracheal intubation and/or death. Moreover, early NIV (P/F > 200 mmHg) treatment seems to reduce the risk of ICU mortality at 28 days from ICU admission.

Concomitant Parenchymal, Subarachnoid, and Ventricular Neurocysticercosis in Rome, Italy: A Case Report with a 4-Year Follow-Up.

Neurocysticercosis (NCC) is caused by the larval stage of Taenia solium. This parasitic disease is endemic in many areas of the world and is emerging in Europe. NCC can affect different brain regions, but simultaneous involvement of the parenchymal, subarachnoid, and ventricular regions is rare. We report the case of a 39-year-old woman from Honduras, resident in Rome for 10 years, who presented to the Emergency Department complaining of headaches, transient hemianopsia, and bilateral papilledema. MRI showed a concomitant parenchymal, subarachnoid, and ventricular involvement in the brain. T. solium IgG antibodies were detected in the blood. The etiological diagnosis of NCC was obtained by identifying T. solium in cerebrospinal fluid using Next Generation Sequencing. Endoscopic neurosurgery with the placement of a ventricular shunt and medical long-term anti-parasitic treatment with a cumulative number of 463 days of albendazole and 80 days of praziquantel were performed. A successful 4-year follow-up is reported. NCC is one of the most common parasitic infections of the human CNS, but it is still a neglected tropical disease and is considered to be an emerging disease in Europe. Its diagnosis and clinical management remain a challenge, especially for European clinicians.

Safety of meglumine gadoterate (Gd-DOTA)-enhanced MRI compared to unenhanced MRI in patients with chronic kidney disease (RESCUE study).

OBJECTIVE: To prospectively compare the renal safety of meglumine gadoterate (Gd-DOTA)-enhanced magnetic resonance imaging (MRI) to a control group (unenhanced MRI) in high-risk patients. METHODS: Patients with chronic kidney disease (CKD) scheduled for MRI procedures were screened. The primary endpoint was the percentage of patients with an elevation of serum creatinine levels, measured 72 ± 24 h after the MRI procedure, by at least 25 % or 44.2 µmol/l (0.5 mg/dl) from baseline. A non-inferiority margin of the between-group difference was set at -15 % for statistical analysis of the primary endpoint. Main secondary endpoints were the variation in serum creatinine and eGFR values between baseline and 72 ± 24 h after MRI and the percentage of patients with a decrease in eGFR of at least 25 % from baseline. Patients were screened for signs of nephrogenic systemic fibrosis (NSF) at 3-month follow-up. RESULTS: Among the 114 evaluable patients, one (1.4 %) in the Gd-DOTA-MRI group and none in the control group met the criteria of the primary endpoint [Δ = -1.4 %, 95%CI = (-7.9 %; 6.7 %)]. Non-inferiority was therefore demonstrated (P = 0.001). No clinically significant differences were observed between groups for the secondary endpoints. No serious safety events (including NSF) were noted. CONCLUSION: Meglumine gadoterate did not affect renal function and was a safe contrast agent in patients with CKD. KEY POINTS: • Contrast-induced nephropathy (CIN) is a potential problem following gadolinium administration for MRI. • Meglumine gadoterate (Gd-DOTA) appears safe, even in patients with chronic kidney disease. • Gd-DOTA only caused a temporary creatinine level increase in 1/70 such patients. • No case or sign of NSF was detected at 3-month follow-up.

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.

Use of Pembrolizumab for Treatment of Progressive Multifocal Leukoencephalopathy in People Living with HIV.

Progressive Multifocal Leukoencephalopathy (PML) is a demyelinating disease occurring in advanced HIV infection, caused by the reactivation of poliomavirus JC (JCV). The use of pembrolizumab for treatment is based on the inhibition of programmed cell death protein 1 (PD-1), potentially improving the anti JCV-specific response. We used pembrolizumab with combined antiretroviral treatment (cART) on a compassionate-use basis. At each administration, clinical evaluation, MRI and laboratory testing, including CD3, CD4, CD8, PD-1 markers, HIV-RNA and JCV-DNA in cerebrospinal fluid (CSF)/plasma pairs, were performed. The JCV-specific T cell response was analysed by Elispot assay. This study included five HIV patients: four male, median age 43 years (29-52), median CD4 and CD8 count 150 (15-158) and 973 (354-1250) cell/mm3, respectively; median JCV-DNA and HIV-RNA in CSF/plasma pairs 9.540/1.503 cps/mL and 2.230/619 cp/mL, respectively. Overall, patients received between two and seven doses of pembrolizumab. After treatment, we observed JCV-DNA reduction and PD-1 down-regulation both in CSF and in plasma (high in circulating CD4 and CD8 at baseline), which remained stable at low levels in all patients. Three out of five patients showed stability of clinical picture and neuroimaging, while two others died. More data are needed in order to identify predictors of response to therapy.

Epidemiology, Clinical Presentation and Treatment of Non-Hepatic Hyperammonemia in ICU COVID-19 Patients.

(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.

Epidemiology of ventilator-associated pneumonia in ICU COVID-19 patients: an alarming high rate of multidrug-resistant bacteria.

BACKGROUND: COVID­19 is a novel cause of acute respiratory distress syndrome (ARDS) that leads patients to intensive care unit (ICU) admission requiring invasive ventilation, who consequently are at risk of developing of ventilator­associated pneumonia (VAP). The aim of this study was to assess the incidence, antimicrobial resistance, risk factors, and outcome of VAP in ICU COVID-19 patients in invasive mechanical ventilation (MV). METHODS: Observational prospective study including adult ICU admissions between January 1, 2021, and June 31, 2021, with confirmed COVID-19 diagnosis were recorded daily, including demographics, medical history, ICU clinical data, etiology of VAPs, and the outcome. The diagnosis of VAP was based on multi-criteria decision analysis which included a combination of radiological, clinical, and microbiological criteria in ICU patients in MV for at least 48 h. RESULTS: Two hundred eighty-four COVID-19 patients in MV were admitted in ICU. Ninety-four patients (33%) had VAP during the ICU stay, of which 85 had a single episode of VAP and 9 multiple episodes. The median time of onset of VAP from intubation were 8 days (IQR, 5-13). The overall incidence of VAP was of 13.48 episodes per 1000 days in MV. The main etiological agent was Pseudomonas aeruginosa (39.8% of all VAPs) followed by Klebsiella spp. (16.5%); of them, 41.4% and 17.6% were carbapenem resistant, respectively. Patients during the mechanical ventilation in orotracheal intubation (OTI) had a higher incidence than those in tracheostomy, 16.46 and 9.8 episodes per 1000-MV day, respectively. An increased risk of VAP was reported in patients receiving blood transfusion (OR 2.13, 95% CI 1.26-3.59, p = 0.005) or therapy with Tocilizumab/Sarilumab (OR 2.08, 95% CI 1.12-3.84, p = 0.02). The pronation and PaO2/FiO2 ratio at ICU admission were not significantly associated with the development of VAPs. Furthermore, VAP episodes did not increase the risk of death in ICU COVID-19 patients. CONCLUSIONS: COVID-19 patients have a higher incidence of VAP compared to the general ICU population, but it is similar to that of ICU ARDS patients in the pre-COVID-19 period. Interleukin-6 inhibitors and blood transfusions may increase the risk of VAP. The widespread use of empirical antibiotics in these patients should be avoided to reduce the selecting pressure on the growth of multidrug-resistant bacteria by implementing infection control measures and antimicrobial stewardship programs even before ICU admission.

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.

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.

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.

Incidence of Pneumothorax and Pneumomediastinum in 497 COVID-19 Patients with Moderate-Severe ARDS over a Year of the Pandemic: An Observational Study in an Italian Third Level COVID-19 Hospital.

(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.

Outcomes and Timing of Bedside Percutaneous Tracheostomy of COVID-19 Patients over a Year in the Intensive Care Unit.

BACKGROUND: The benefits and timing of percutaneous dilatational tracheostomy (PDT) in Intensive Care Unit (ICU) COVID-19 patients are still controversial. PDT is considered a high-risk procedure for the transmission of SARS-CoV-2 to healthcare workers (HCWs). The present study analyzed the optimal timing of PDT, the clinical outcomes of patients undergoing PDT, and the safety of HCWs performing PDT. METHODS: Of the 133 COVID-19 patients who underwent PDT in our ICU from 1 April 2020 to 31 March 2021, 13 patients were excluded, and 120 patients were enrolled. A trained medical team was dedicated to the PDT procedure. Demographic, clinical history, and outcome data were collected. Patients who underwent PDT were stratified into two groups: an early group (PDT ≤ 12 days after orotracheal intubation (OTI) and a late group (>12 days after OTI). An HCW surveillance program was also performed. RESULTS: The early group included 61 patients and the late group included 59 patients. The early group patients had a shorter ICU length of stay and fewer days of mechanical ventilation than the late group (p < 0.001). On day 7 after tracheostomy, early group patients required fewer intravenous anesthetic drugs and experienced an improvement of the ventilation parameters PaO2/FiO2 ratio, PEEP, and FiO2 (p < 0.001). No difference in the case fatality ratio between the two groups was observed. No SARS-CoV-2 infections were reported in the HCWs performing the PDTs. CONCLUSIONS: PDT was safe and effective for COVID-19 patients since it improved respiratory support parameters, reduced ICU length of stay and duration of mechanical ventilation, and optimized the weaning process. The procedure was safe for all HCWs involved in the dedicated medical team. The development of standardized early PDT protocols should be implemented, and PDT could be considered a first-line approach in ICU COVID-19 patients requiring prolonged mechanical ventilation.

Risk and predictive factors of prolonged viral RNA shedding in upper respiratory specimens in a large cohort of COVID-19 patients admitted to an Italian reference hospital.

BACKGROUND: Limited data are available about the predictors and outcomes associated with prolonged SARS-CoV-2 RNA shedding (VS). METHODS: 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. RESULTS: 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 >1000ng/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. CONCLUSIONS: 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.

Functional Magnetic Resonance Imaging in the Olfactory Perception of the Same Stimuli.

BACKGROUND: Data in the literature report that a number of studies have attempted to identify the exact location of the cortical olfaction representation, searching for evidence suggesting that sniffing odors can initiate a primary activation of the piriform cortex and the insula. Nowadays, due to the SARS-CoV-2 (COVID-19) outbreak, the functional study of the olfactory system could offer a better understanding of the physiopathology of olfactory perception, elucidating better the possible site(s) of damage induced by the COVID-19 infection. The aim of this paper was to evaluate brain maps generated from functional Magnetic Resonance Imaging (fMRI) data, collected from healthy individuals in response to the same olfactory stimulus. METHODS: A total of 45 healthy volunteers, without history and/or no clinical signs of sinonasal disease and without history and/or presence of olfactory dysfunction underwent fMRI assessment. Subjects were presented with the same odorous stimuli at specific intervals. fMRI generated brain maps were used in the identification of different cortical areas, involved in the stimuli perception. RESULTS: The fMRI brain maps showed that odorous stimuli activate primarily the left anterior insula (in 35/45 cases or 77.8%). Other activated areas include: the low temporal gyri, the middle and superior temporal gyri, the frontal and piriform cortex, the anterior cingulate gyrus, the parahippocampal gyrus, the temporopolar area, the para-insular area, the subcentral area, the supramarginal gyrus, the occipital cortex and the cerebellum. CONCLUSIONS: fMRI resulted as a safe and reliable means to study the perception of olfaction in the cortex. The data of this study suggest that the anterior insula is the main stimulated area when olfactory stimuli are present. This area is always activated, despite the hand and nostril dominance.

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.

Transpars Microscopic Approach for the Treatment of Purely Foraminal Herniated Lumbar Disc: A Clinical, Radiological, Two-center Study.

STUDY DESIGN: This is a prospective two-center study. OBJECTIVE: The aim of this study was to assess the safety and efficacy of treating patients with lumbar foraminal disc herniations via a microscopic transpars approach, with a clinical and radiological follow-up evaluation. SUMMARY OF BACKGROUND DATA: Purely foraminal lumbar disc herniations comprise about 5% of all lumbar herniated intervertebral discs. Operative management can be technically difficult, and the optimum surgical treatment remains controversial. METHODS: From January 2012 to January 2015, 47 patients were prospectively recruited. Patients were followed-up as outpatients at 1 week after discharge, then at 1, 6, and 12 months.A clinical multiparametric evaluation of patients including numeric rating scale (NRS), drugs intake, Macnab criteria, and working days lost was used.Postoperative dynamic x-rays (flexion, extension) were performed in all cases 12 months after surgery. RESULTS: No surgery-related complications occurred.Among the 35 patients who were not retired at the time of the study, 29 patients returned to work and to normal daily activities within 60 days after surgery.Pain evaluation at discharge showed a significant improvement of NRS score, from 8.93 to 1.45 at 12 months. Root palsy significantly improved in all cases already at 1-month follow-up. Drugs intake analysis showed that at 6-month follow-up, no patients used steroids, or opioids, 17 patients used non-steroidal anti-inflammatory drugs when needed, and 29 patients (61.7%) used no drugs for pain relief. No significant variations occurred at 12-month-follow-up.At 12-month follow-up, excellent or good outcome (following Macnab criteria) was achieved in 36 (76.6%) and 8 (17%) patients, respectively.There were no cases of spinal instability at 12-month radiological evaluation.No recurrence occurred at follow-up. CONCLUSION: Transpars microscopic approach is effective and safe for the treatment of FLDH, but larger studies are needed. LEVEL OF EVIDENCE: 3.

Obstructive jaundice.

The case of a 67-year-old male patient affected by ingravescent obstructive jaundice, calcific choledocholithiasis and cardiopathic hypertension, is presented. On sonography, marked dilatation of intra- and extrahepatic bile ducts with a hyperechoic round neoformation was visualized. CT was performed to ascertain the nature of the lesion. However, it did not confirm the lithiasic nature of the stenosis. Sampling for ERCP was inadequate. Cholangiopancreatography was therefore necessary to establish a correct diagnosis and the subsequent therapeutic approach. Distal choledochal obstruction was evidenced, suspicious for lithiasis obstruction. A definitive diagnosis could not be established on exclusive imaging findings. Surgery was performed with the diagnosis of cholangiocarcinoma with lithiasis.

Reasoned approach to multiple osteosclerotic lesions. Combined diagnostic imaging in a case of osteopoikilosis.

The case of a female patient who had undergone mastectomy for infiltrating ductal carcinoma and come to the Orthopedics Division for lumbosacral pain unresponsive to conventional treatment is discussed. Pelvic X-ray, CT and scintigraphy were performed. The presence of multiple areas of selerosis of the pelvis and proximal femurs were documented. The differential range could be limited to osteoblastic metastasis and osteopoikilosis. The diagnosis of osteopoikilosis was established based on scintigraphy which proved the absence of uptake of the radiotracer.

Perception and reality in a case of suspected cervical fracture.

The case of a 36-year-old female, who following a road accident, had a cervical whiplash, is discussed. A radiographic examination of the affected region was performed at the Emergency Department. It showed a transverse radiolucent line at the basal odontoid process of the axis. A definitive interpretation was not possible and fracture of the odontoid process of the axis was suggested as differential diagnosis. On coronal CT reconstruction the presence of this fracture was ruled out. The line seen on the film was actually the product of a psychophysiologic visual illusion known as "Mach band". The use of conventional radiography correlated with digital CT images shows that the practical application of Mach band theory allows a better differentiation between normal and pathologic anatomy.