Patients with Covid-19 exhibit different immunological profiles according to their clinical presentation.

OBJECTIVES: A novel beta coronavirus has been identified as responsible for the 2019 coronavirus infection (Covid-19). Clinical presentations range from asymptomatic cases to acute respiratory distress syndrome with fatal outcome. Such a broad spectrum of disease expression calls for an investigation of immune response characteristics. METHODS: We identified subjects admitted for Covid-19 in whom a large panel of immunological markers were measured, including B- and T- and NK-lymphocyte phenotypes, T-lymphocyte subpopulation cells and plasma cytokines. Patients were divided according to symptom severity during hospitalisation, in those with uncomplicated and complicated infection. Differences between groups were analyzed. RESULTS: Seventeen patients were included (mean age: 83 years; 9 women; mean delay of symptoms onset: 4 days). Six had uncomplicated infection, while 11 developed complicated forms during hospitalization. CD10 + B lymphocyte levels were inversely correlated with clinical severity (5.8% vs 2.0%, p = 0.04) and CD10+ levels above 3% were independently associated with uncomplicated forms [Odds Ratio 0.04 (CI 0.002-0.795, p = 0.034)]. TNF-alpha, IL-1, Il-6 and Il-8 measurements upon admission differed between patients who died and those who survived (p < 0.01 for all comparisons). CONCLUSIONS: In a population of elderly patients recently infected with Covid-19, CD10 + B cell levels were inversely correlated with clinical severity. Cytokine values upon admission were highly predictive of fatal outcome during hospitalisation. These findings could explain differences in the clinical presentation and allow rapid identification of patients at risk for complications.

Lung ultrasonography in pulmonary tuberculosis: A pilot study on diagnostic accuracy in a high-risk population.

OBJECTIVES: The validity of lung ultrasound (LUS) in the diagnosis of interstitial or focal lung pathologies is well documented, we assessed its accuracy in the diagnosis of pulmonary tuberculosis (PTB). METHODS: Sonographic signs suggestive of PTB and their diagnostic accuracy were evaluated in patients admitted with clinical suspicion of PTB. Consolidations, subpleural nodules, pleural thickenings or irregularities and pleural effusion were assessed. LUS signs significantly associated with PTB in the univariate analysis (p < .05) were entered in a multivariate logistic regression model. RESULTS: PTB was confirmed in 51 out of 102 patients. Multiple consolidations (OR 3.54, 95%CI 1.43-8.78), apical consolidations (OR 9.65, 95%CI 3.02-30.78), superior quadrant consolidations (OR 4.01, 95%CI 1.76-9.14), and subpleural nodules (OR 5.29, 95%CI 2.27-12.33) were significantly associated with PTB diagnosis. Apical consolidation (OR 9.67, 95%CI 2.81-33.25, p 0.003) and subpleural nodules (OR 5.30, 95%CI 2.08-13.52, p 0.005) retained a significant association in a multivariate model, with an overall accuracy of 0.799. CONCLUSIONS: Our data suggest a possible role of LUS in the diagnosis of PTB, a high burden pathological condition for which the delay in diagnosis still represents a critical point in the control of the disease.

Prognostic Potential of the Panfungal Marker (1 → 3)-ß-D-Glucan in Invasive Mycoses Patients.

We analyze the prognostic potential of (1 → 3)-ß-D-glucan (BG) levels in predicting clinical outcomes in patients with invasive fungal infections, on a population undergoing 253 episodes (177 with positive and 76 with negative outcome). Using linear regression analysis, we assessed the prognostic potential of kinetically evaluated BG levels and we found an overall sensitivity and specificity of 68 and 82%, respectively. Moreover, using an interpretative algorithm based on two distinct cutoff values, we were able to predict the outcome in 84% of the studied population with a diagnostic accuracy of 82%.

Evaluation of serum (1 → 3)-ß-D-glucan clinical performance: kinetic assessment, comparison with galactomannan and evaluation of confounding factors.

PURPOSE: We investigated the clinical performance of (1 → 3)-ß-D-glucan (BG), as an early marker of invasive fungal infections (IFI), in different clinical settings. METHODS: BG serum levels were assessed by Fungitell (Associates of Cape Cod, Inc), in parallel with galactomannan (GM) when requested by clinicians. By a prospective monocentric study, 270 episodes at risk or with suspect of IFI were enrolled, namely 58 proven-probable invasive aspergillosis (IA), 27 proven invasive candidiasis (IC), 11 possible IC, 16 P.jirovecii pneumonia (PJP), 4 episodes of other IFI and 154 non-IFI controls. RESULTS: We found that (a) the BG overall sensitivity, specificity, positive predictive value and negative predictive value (NPV) were 87.9, 80.5, 76.7 and 89.9 %, respectively; (b) the highest sensitivity was found in the IC groups, followed by PJP, IA and other IFI groups; (c) an association was observed between BG kinetics and patients outcome; (d) in the IA episodes, the combination of BG or GM vs GM alone increased sensitivity from 60.0 to 83.3 % in the haematological patients; (e) false-positive BG results were related to Gram-negative infections or infusion of polyclonal IgM-enriched immunoglobulins, where high levels of BG were indeed detected. CONCLUSION: Besides strengthening its overall good clinical performance, we provide evidence that serum BG correlates with clinical outcome and that, once used in combination with GM, BG allows to enhance IFI diagnosis rate. The high sensitivity and NPV, observed in the Intensive Care Unit setting, open to BG validation as a marker for assessment of antifungal treatment.

Clinical performance of a commercial real-time PCR assay for Aspergillus DNA detection in serum samples from high-risk patients: comparison with a galactomannan enzyme immunoassay.

We investigated the clinical performance of a polymerase chain reaction (PCR)-based commercial platform, the Myconostica MycAssay™ Aspergillus (MAP), for fungal DNA detection in the serum of patients at risk of invasive aspergillosis (IA). Sixty-four hospitalized patients were prospectively enrolled and a total of 71 different episodes were investigated (30 episodes were clinically/microbiologically classified as IA and 41 as control episodes). When MAP was compared to the galactomannan (GM) assay, no significant differences were found in terms of sensitivity (46.7% vs. 50.0%), specificity (97.6% vs. 95.1%), positive predictive value (PPV) (93.3% vs. 88.2%), and negative predictive value (NPV) (71.4% vs. 72.2%). The corresponding areas under the curve (AUC) of the receiver operating characteristic (ROC) curves were also superimposable. Overall, because of the good agreement between the two assays and considering the high specificity and PPV of the MAP, we suggest the use of this PCR-based platform as a second-level examination for the evaluation of clinically undefined cases where culture or GM have provided positive results.

Routine use of a protease zymogen-based colorimetric assay for the detection of Beta-glucan and its role in clinical practice.

The detection of Aspergillus antigen (galactomannan) is considered a reliable marker for the diagnosis of invasive aspergillosis (IA), yet the sensibility and specificity of the assays commonly employed in routine are not optimal. The aim of the present study was to investigate whether the detection of another panfungal antigen, the (1,3)-b-D-glucan could have an auxiliary role in the identification of patients with IA. The study was carried out on 63 sera belonging to patients who had been screened for galactomannan, according to the clinical suspect of IA. Our data show that the positive galactomannan results were not confirmed by positive (1,3)-b-D-glucan results in patients receiving therapy with beta-lactam antibiotics associated with tazobactam, whereas in all the other cases, with the exception of four, the results of the (1,3)-b-D-glucan test were confirmatory of the galactomannan results.

Acute systemic, splanchnic and renal haemodynamic changes induced by molecular adsorbent recirculating system (MARS) treatment in patients with end-stage cirrhosis.

AIM: To evaluate the acute effect of treatment with the molecular adsorbent recirculating system (MARS) on splanchnic, renal and systemic haemodynamics in patients with end-stage cirrhosis. METHODS: Twelve patients with end-stage cirrhosis, undergoing MARS treatment, were enrolled. The following haemodynamic parameters were measured by means of Doppler ultrasonography and thoracic electrical bioimpedance, before and after each session: portal velocity, renal and splenic resistance indices, cardiac output, cardiac stroke volume, heart rate, mean arterial pressure, systemic vascular resistance. RESULTS: Median portal velocity increased significantly after treatment (23.7 vs. 20.3 cm/s, P < 0.05) while renal resistance index (0.72 vs. 0.75, P < 0.05) and splenic resistance index (0.60 vs. 0.65, P < 0.05) decreased significantly. Mean arterial pressure (83 vs. 81 mmHg, P < 0.05) and vascular resistance (899 vs. 749 dyne. s/cm5, P < 0.05) increased significantly, while cardiac output and stroke volume showed no significant changes. CONCLUSIONS: Data emerging from this investigation suggest that MARS treatment improves significantly various haemodynamic alterations in cirrhotic patients in the short term. The observed decrease in renal vascular resistance and improvement in splenic resistance index, a parameter related to portal resistance, which leads us to hypothesize that these haemodynamic effects are probably mediated by clearance of vasoactive substances during MARS treatment.

A comparative study of Endoflare-Hero Shaper and Mtwo NiTi instruments in the preparation of curved root canals.

AIM: To analyse the shaping ability of two new NiTi rotary systems in molar curved canals. METHODOLOGY: Thirty molar root canals with curvatures from 24 degrees to 69 degrees were divided into two groups that were balanced in terms of curvature. The canals in one group were shaped using the Mtwo (Sweden & Martina, Padova, Italy) and the canals in the other group using the Endoflare-Hero Shaper (Micro-Mega, Besançon, France) in a modified sequence. Pre- and post-instrumentation X-rays were taken using a radiographic platform, with a contrast medium being used to enhance canal opacity. The dentine removed at five positions along the canals, the symmetry of canal shaping and the presence of aberrations were analysed through computer-aided measurements. The instrument failures, the working time and the changes in working length were also recorded. The Mann-Whitney U-test was used for statistical analyses. RESULTS: Both systems produced uniform dentine removal and symmetrical canal shapes; there was no significant difference between the systems (P > 0.05). In the apical region, preparations were centred in the canal. A mean loss of working length of 0.55 mm for Mtwo and 0.58 mm for Endoflare-Hero Shaper was detected, with no significant differences between the instruments (P > 0.05). No aberrations were seen and no instruments separated. The mean working time was 124.4 s for the Mtwo system and 141.3 s for the Endoflare-Hero Shaper but this difference was not statistically significant (P > 0.05). CONCLUSION: The systems tested in this study were effective in shaping curved canals in extracted teeth.

Influence of the spleen on portal haemodynamics: a non-invasive study with Doppler ultrasound in chronic liver disease and haematological disorders.

BACKGROUND: Splanchnic haemodynamic parameters for the differential diagnosis of splenomegalies of different origins are still suboptimal and the role of spleen enlargement in cirrhosis remains controversial. In an attempt to elucidate these questions, we assessed splanchnic haemodynamics in chronic liver diseases and various other disorders with splenomegaly. METHODS: Study groups comprised: (i) patients with chronic liver disease (89 with cirrhosis, 35 with chronic hepatitis), (ii) patients with splenomegaly without relevant portal hypertension (14 with haematological splenomegaly and 25 liver transplant recipients without complications), (iii) 15 patients with arterial hypertension, (iv) 22 healthy controls. In all subjects, spleen size, portal flow parameters and splenic artery resistance index were measured using duplex-Doppler ultrasound. RESULTS: Splenic artery resistance index was significantly and selectively increased in patients with cirrhosis (0.63, whereas all other group means ranged between 0.53 and 0.56; P < 0.01). Portal flow velocity was significantly decreased in cirrhosis (P < 0.01). The combination of these two parameters provided an accuracy of 87.5% in distinguishing portal hypertensive from haematological splenomegaly. In patients with cirrhosis, the degree of spleen enlargement was positively correlated with increasing portal flow volume, portal vein diameter and variceal size, whereas splenic resistance index and portal velocity did not differ in connection with spleen size. CONCLUSIONS: Splenoportal Doppler sonography provides specific findings in cirrhosis and may therefore be a useful tool in differentiating between splenomegaly of portal hypertensive or haematological origin. In patients with cirrhosis, the presence of splenomegaly is associated with the presence of larger oesophageal varices.

Cerebellar mature teratoma in adulthood.

Mature teratoma of the posterior cranial fossa in adults is extremely rare. We report a particularly rare case of medio-lateral cerebellar mature teratoma that became symptomatic in a middle-aged man. The CT revealed the lesion of heterogeneous density with calcifications in the solid medial portion. Only the MRI could reliably define the borders of the cystic component extending into the left cerebellar lobe. Histologically the presence of fully matured representative tissues of the 3 germ layers ensured the diagnosis of mature teratoma. We suggest that the cyst formation from progressive latent hemorrhage and/or secretion from the gland cells of the tumor, may be responsible for the clinical decompensation even in adulthood.