Considerations on COVID-19 pregnancy: a cases series during outbreak in Bergamo Province, North Italy.

BACKGROUND: COVID-19 has rapidly spread worldwide, with severe complications affecting particularly elderly and compromised subjects. Less information about COVID-19 in pregnancy has been reported so far in the literature. METHODS: Case series on pregnancies complicated by COVID-19. All cases were diagnosed at Bolognini Hospital, Seriate, Italy. These cases are presented to clarify the features of COVID-19 occurring in pregnancy. RESULTS: Four women had symptoms of COVID-19 during pregnancy or immediately after delivery. All cases were confirmed by oropharyngeal swab. All patients presented with fever and low saturation levels at the diagnosis. One case was transferred after diagnosis to a tertiary referral center and delivered the day after for worsening clinical conditions. In the other three cases, bilateral pneumonia was documented at the admission. Antithrombotic therapy was used in most cases. No cases of the infected neonate was reported. At 2 month follow-up, all patients were alive, three were asymptomatic while one presented neurological complication. One more case was described because suspicious for COVID-19, however, it was not confirmed by oropharyngeal swab. CONCLUSIONS: In pregnant women, the peripheral nervous system could be affected. No case of trans-placental passage was reported. The swab could be helpful in diagnosis. The antithrombotic therapy could play a role in the positive course of COVID-19 also in pregnant women.

Acute severe autoimmune hepatitis with anti-rods and rings autoantibodies; literature first evidence.

Autoimmune hepatitis (AIH) was defined as a progressive, chronic inflammatory autoimmune liver disease (ALD). The diagnosis of AIH requires the presence of characteristic clinical and laboratory features, and the exclusion of other clinical conditions that cause chronic hepatitis and cirrhosis. AIH can have an acute onset that mimics an acute viral or toxic hepatitis or an acute severe (fulminant, ASF) presentation that satisfies criteria for acute liver. Guidelines from the European Association for the Study of Liver Diseases define ALF with absence of pre-existing liver disease, acute onset of ≤ 26 weeks, coagulopathy (international normalised ratio (INR) ≥ 1.5), and presence of hepatic encephalopathy (HE). In recent years, autoantibodies (Aab) targeting subcellular structures described as the rods and rings (R&R) pattern in HEp-2 ANA have been presented as a unique and particular case of Aab generation. These R&R structures are composed of inosine monophosphate dehydrogenase type 2 (IMPDH2), and their formation can be induced in vitro by several small-molecule inhibitors. Aab targeting these relatively unknown structures has been observed in Hepatitis C virus (HCV) patients who have undergone treatment with pegylated interferona/ ribavirin (IFN/RBV) therapy. We presented and characterized a case patient with R&R and SMA Aab in AIH (ASF, fatal, without liver transplantation). To the best of our knowledge, this is the first evidence described in the Literature. Our early experience showed the R&R circulating Aab in one patient with Primary Biliary Cholangitis. This work now demonstrates that R&R Aab can also be present in AIH case.

Coronavirus Disease 2019 (COVID-19) in Italy: Double Reading of Chest CT Examination.

To assess the performance of the second reading of chest compute tomography (CT) examinations by expert radiologists in patients with discordance between the reverse transcription real-time fluorescence polymerase chain reaction (RT-PCR) test for COVID-19 viral pneumonia and the CT report. Three hundred and seventy-eight patients were included in this retrospective study (121 women and 257 men; 71 years median age, with a range of 29-93 years) and subjected to RT-PCR tests for suspicious COVID-19 infection. All patients were subjected to CT examination in order to evaluate the pulmonary disease involvement by COVID-19. CT images were reviewed first by two radiologists who identified COVID-19 typical CT patterns and then reanalyzed by another two radiologists using a CT structured report for COVID-19 diagnosis. Weighted к values were used to evaluate the inter-reader agreement. The median temporal window between RT-PCRs execution and CT scan was zero days with a range of (-9,11) days. The RT-PCR test was positive in 328/378 (86.8%). Discordance between RT-PCR and CT findings for viral pneumonia was revealed in 60 cases. The second reading changed the CT diagnosis in 16/60 (26.7%) cases contributing to an increase the concordance with the RT-PCR. Among these 60 cases, eight were false negative with positive RT-PCR, and 36 were false positive with negative RT-PCR. Sensitivity, specificity, positive predictive value and negative predictive value of CT were respectively of 97.3%, 53.8%, 89.0%, and 88.4%. Double reading of CT scans and expert second readers could increase the diagnostic confidence of radiological interpretation in COVID-19 patients.

Cryptococcal-related meningoencephalitis in a patient with sarcoidosis and CD4 lymphocytopenia: thorough immunological characterization of lymphocyte homeostasis.

Cryptococcal meningoencephalitis is the most common infective complication observed in patients with CD4 lymphocytopenia, including sarcoidosis. T-cell immunity is well characterized in HIV-related infections and data regarding immunity in cryptococcosis animal models is now available; on the contrary, little is known about the immune status in non-HIV-related infections. We report on reduced production of new T cells observed in a patient with sarcoidosis, CD4 lymphocytopenia, and cryptococcal-related meningoencephalitis. Although T cells presented with an intact proliferative capacity, they were oligoclonally expanded showing an effector memory phenotype. However, the deleterious activity of effector memory cells could have been controlled by the expansion of the regulatory T cell subset with the highest suppressive capability. This information provides a better understanding of the immune response to Cryptococcus occurring in non-HIV-associated cases, the predisposition to infection, and the role of different cell subtypes in controlling the disease in humans.

COVID-19 pneumonia: computer-aided quantification of healthy lung parenchyma, emphysema, ground glass and consolidation on chest computed tomography (CT).

OBJECTIVE: To calculate by means of a computer-aided tool the volumes of healthy residual lung parenchyma, of emphysema, of ground glass opacity (GGO) and of consolidation on chest computed tomography (CT) in patients with suspected viral pneumonia by COVID-19. MATERIALS AND METHODS: This study included 116 patients that for suspected COVID-19 infection were subjected to the reverse transcription real-time fluorescence polymerase chain reaction (RT-PCR) test. A computer-aided tool was used to calculate on chest CT images healthy residual lung parenchyma, emphysema, GGO and consolidation volumes for both right and left lung. Expert radiologists, in consensus, assessed the CT images using a structured report and attributed a radiological severity score at the disease pulmonary involvement using a scale of five levels. Nonparametric test was performed to assess differences statistically significant among groups. RESULTS: GGO was the most represented feature in suspected CT by COVID-19 infection; it is present in 102/109 (93.6%) patients with a volume percentage value of 19.50% and a median value of 0.64 L, while the emphysema and consolidation volumes were low (0.01 L and 0.03 L, respectively). Among quantified volume, only GGO volume had a difference statistically significant between the group of patients with suspected versus non-suspected CT for COVID-19 (p < < 0.01). There were differences statistically significant among the groups based on radiological severity score in terms of healthy residual parenchyma volume, of GGO volume and of consolidations volume (p < < 0.001). CONCLUSION: We demonstrated that, using a computer-aided tool, the COVID-19 pneumonia was mirrored with a percentage median value of GGO of 19.50% and that only GGO volume had a difference significant between the patients with suspected or non-suspected CT for COVID-19 infection.

Modified Corona Score can easily identify Covid-19 patients with gastrointestinal symptoms: An Italian proposal.

AIM: We propose the Modified Corona Score (MCorona score), an alternative approach to identifying new likely Covid-19 patients without positive chest images, but with gastrointestinal onset. BACKGROUND: In April, 2020, a total of 104,291 laboratory-confirmed cases had been documented in Italy; Lombardy, the Northern Italian Region, recorded over 60,000 Covid-19 cases. METHOD: The MCorona score is built by several laboratory parameters linked between age and gender, ranging from 0 to 10. RESULTS: Using the preliminary score cut-off of 4, we successfully identified likely Covid-19 patients with gastrointestinal onset. However, more caution is needed, and a larger sample size is required to verify the accuracy and specificity of the score. CONCLUSION: We propose the complete validation of the MCorona score, an instrument able to diagnose likely Covid-19 patients with symptoms other than respiratory distress.

Coronavirus disease 2019 (COVID-19) in Italy: features on chest computed tomography using a structured report system.

To assess the use of a structured report in the Chest Computed Tomography (CT) reporting of patients with suspicious viral pneumonia by COVID-19 and the evaluation of the main CT patterns. This study included 134 patients (43 women and 91 men; 68.8 years of mean age, range 29-93 years) with suspicious COVID-19 viral infection evaluated by reverse transcription real-time fluorescence polymerase chain reaction (RT-PCR) test. All patients underwent CT examinations at the time of admission. CT images were reviewed by two radiologists who identified COVID-19 CT patterns using a structured reports. Temporal difference mean value between RT-PCRs and CT scan was 0.18 days ± 2.0 days. CT findings were positive for viral pneumonia in 94.0% patients while COVID-19 was diagnosed at RT-PCR in 77.6% patients. Time mean value to complete the structured report by radiologist was 8.5 min ± 2.4 min. The disease on chest CT predominantly affected multiple lobes and the main CT feature was ground glass opacity (GGO) with or without consolidation (96.8%). GGO was predominantly bilateral (89.3%), peripheral (80.3%), multifocal/patching (70.5%). Consolidation disease was predominantly bilateral (83.9%) with prevalent peripheral (87.1%) and segmental (47.3%) distribution. Additional CT signs were the crazy-paving pattern in 75.4% of patients, the septal thickening in 37.3% of patients, the air bronchogram sign in 39.7% and the "reversed halo" sign in 23.8%. Less frequent characteristics at CT regard discrete pulmonary nodules, increased trunk diameter of the pulmonary artery, pleural effusion and pericardium effusion (7.9%, 6.3%, 14.3% and 16.7%, respectively). Barotrauma sign was absent in all the patients. High percentage (54.8%) of the patients had mediastinal lymphadenopathy. Using a Chest CT structured report, with a standardized language, we identified that the cardinal hallmarks of COVID-19 infection were bilateral, peripheral and multifocal/patching GGO and bilateral consolidation with peripheral and segmental distribution.

Chest CT Computerized Aided Quantification of PNEUMONIA Lesions in COVID-19 Infection: A Comparison among Three Commercial Software.

PURPOSE: To compare different commercial software in the quantification of Pneumonia Lesions in COVID-19 infection and to stratify the patients based on the disease severity using on chest computed tomography (CT) images. MATERIALS AND METHODS: We retrospectively examined 162 patients with confirmed COVID-19 infection by reverse transcriptase-polymerase chain reaction (RT-PCR) test. All cases were evaluated separately by radiologists (visually) and by using three computer software programs: (1) Thoracic VCAR software, GE Healthcare, United States; (2) Myrian, Intrasense, France; (3) InferRead, InferVision Europe, Wiesbaden, Germany. The degree of lesions was visually scored by the radiologist using a score on 5 levels (none, mild, moderate, severe, and critic). The parameters obtained using the computer tools included healthy residual lung parenchyma, ground-glass opacity area, and consolidation volume. Intraclass coefficient (ICC), Spearman correlation analysis, and non-parametric tests were performed. RESULTS: Thoracic VCAR software was not able to perform volumes segmentation in 26/162 (16.0%) cases, Myrian software in 12/162 (7.4%) patients while InferRead software in 61/162 (37.7%) patients. A great variability (ICC ranged for 0.17 to 0.51) was detected among the quantitative measurements of the residual healthy lung parenchyma volume, GGO, and consolidations volumes calculated by different computer tools. The overall radiological severity score was moderately correlated with the residual healthy lung parenchyma volume obtained by ThoracicVCAR or Myrian software, with the GGO area obtained by the ThoracicVCAR tool and with consolidation volume obtained by Myrian software. Quantified volumes by InferRead software had a low correlation with the overall radiological severity score. CONCLUSIONS: Computer-aided pneumonia quantification could be an easy and feasible way to stratify COVID-19 cases according to severity; however, a great variability among quantitative measurements provided by computer tools should be considered.

Laboratory markers included in the Corona Score can identify false negative results on COVID-19 RT-PCR in the emergency room.

After December 2019 outbreak in China, the novel Coronavirus infection (COVID-19) has very quickly overflowed worldwide. Infection causes a clinical syndrome encompassing a wide range of clinical features, from asymptomatic or oligosymptomatic course to acute respiratory distress and death. In a very recent work we preliminarily observed that several laboratory tests have been shown as characteristically altered in COVID-19. We aimed to use the Corona score, a validated point-based algorithm to predict the likelihood of COVID-19 infection in patients presenting at the Emergency rooms. This approach combines chest images-relative score and several laboratory parameters to classify emergency room patients. Corona score accuracy was satisfactory, increasing the detection of positive patients' rate.

Laboratory Biomarkers Predicting COVID-19 Severity in the Emergency Room.

Infection of novel Coronavirus has been declared pandemic by the WHO and now is a world public health crisis. Laboratory activity becames essential for the timely diagnosis. Few parameters, such Lymphocytes count, SaO2 and CRP serum level can be used to assess the severity of COVID-19 in emergency room.

Diagnosis of gluten-related enteropathy in a newborn: how and when?

AIM: To analyze the development of gliadin-specific immune responses in children with a genetic risk for CD and to determine whether these could be detected before the clinical onset of the disease by using immunological tests. BACKGROUND: Clinical manifestations of celiac disease (CD) in the first year of life is uncommon, which is due to the suboptimal sensitivity of tissue transglutaminase IgA antibodies (tTG-IgA) at this age and other possible causes of malabsorption in infants. The development of Deamidate gliadin peptide-specific antibodies (in particular DGP-IgG) in young children was poorly considered in the CD diagnosis. METHODS: We conducted a retrospective cross-sectional study on children between one month and forty-eight months of life, which performed in our health center from 2016 to 2018. Three hundred and fifty children were selected according to strict inclusion criteria: positive for HLA-DQA1 and DQB1 alleles, positive anti tTG-IgA/IgG and/or positive DGP-IgG/IgA. Eighty-two children were selected and divided into two different groups of patients: Group one (forty newborns under twenty-four months of life) and Group two (children from twenty-five months to 48 months of life). RESULTS: Anti-DGP-IgG antibodies precede anti tTG-IgA seroconversion in children under two years in 80% of cases. Anti-DGP-IgG positive patients had milder symptomatic forms of CD than anti tTG-IgA positive children, characterized by gastrointestinal symptoms in the presence of normal growth, normal serum iron, and low MCH level. At tTG-IgA seroconversion, children present gastrointestinal clinical forms associated with impaired growth. The combined use of tTG-IgA and DGP-IgG antibodies upgrade the diagnostic sensitivity from 50% to 92%. CONCLUSION: Anti-DGP-IgG antibodies precede tTG-IgA seroconversion in newborns and identified two distinct clinical phenotypes. At this point, if you wanted to test your newborn patients for CD serology, how would you proceed?

Pentraxin 3 and biopsy status in celiac patients.

AIM: In our study we explored a possible relationship between PTX3 and CD. BACKGROUND: Gluten sensitivity is known as a hallmark of celiac disease (CD). The diagnosis of CD requires demonstration of a typical enteropathy, and positive serology supports the diagnosis. The CD immune response involves the adaptive, as well as the innate immunity and is characterized by the presence of anti-gliadin (AGA) and anti-transglutaminase 2 antibodies (tTGA), lymphocytic infiltration in the intestinal epithelial membrane and expression of multiple cytokines. The long pentraxin 3 (PTX3), an acute-phase inflammatory molecule, plays an important role in innate immunity. METHODS: 108 CD patients were divided according to Marsh Histological grade following Marsh criteria classification in three groups: Group 1: Marsh 0, patients with a known history of CD under gluten free diet, complete remission; Group 2: Marsh1 and Marsh 2; Group 3: Marsh 3. Healthy age-matched controls without a known history of CD or gastrointestinal symptoms (n=30) served as controls. PTX3 serum levels were measured by sandwich ELISA on an automated platform. RESULTS: PTX3 serum levels were significantly elevated in group 3 and group 2 compared with HC (mean 3.31± 1.27 ng/mL and 3.97 ± 0.54 ng/mL versus 1.06 ± 0.59 ng/mL; P < 0.005), with group 1 (0.76±0.31 ng/mL). No statistically significant differences were found between group 1 and HC group. We found a strong linear correlation between PTX3 serum levels and AGA levels in group 2 (r=0.78, P <0.0001), and group 3 (r =0.63, P < 0.005) but no correlations were detected between PTX3 serum levels and tTGA levels (group 2, r= 0.04; group 3, r=0.24). Serological data revealed that PTX3 correlated with major gastrointestinal damage patients. CONCLUSION: PTX3 is a component of the humoral arm of the innate immune system. Our data showed that PTX3 serum levels were high in active disease patients with pathological levels of AGA. We also demonstrated that patients with normal AGA IgA levels had PTX3 serum levels compared to healthy control. We hypothesized that PTX3 is able to modulate the innate response to gliadin in CD and it could regulate the adaptive immune response.

Comparison of ß2-microglobulin serum level between Alzheimer's patients, cognitive healthy and mild cognitive impaired individuals.

BACKGROUND: Several studies performed in the last years on the brain, showed that beta2-microglobulin (ß2m) and MHC can act independently of their canonical immune function to regulate normal brain development, synaptic plasticity and behaviour. Increased systemic levels of soluble ß2m have been implicated in cognitive impairments like that associated with chronic haemodialysis, or aortic valve replacement. Increased soluble ß2m has also been detected in the cerebral spinal fluid (CSF) of patients with HIV-associated dementia and Alzheimer's disease (AD). OBJECTIVE: To compare plasma ß2m levels in healthy subjects and subjects with dementia or cognitive impairment. METHODS: We measured the concentration of ß2m in a cohort of 245 individuals and compared sex matched, cognitive healthy individuals. RESULTS: We found higher levels of ß2m in AD patients compared to non-AD MCI and healthy controls (2063 ng/mL ±852 versus 1613 ± 503 and 1832 ± 382 ng/mL, p< 0.001 and <0.033, respectively), while there was no difference between mild cognitive impairment (MCI) and healthy controls (p > 0.05). CONCLUSIONS: Our data confirm that ß2m could play a role in AD. However, a replication study in an independent cohort would be necessary to confirm our preliminary results.

Maternal T-cell engraftment impedes with diagnosis of a SCID-ADA patient.

We describe the case of a child affected by severe combined immunodeficiency (SCID) with adenosine deaminase (ADA) deficiency showing a maternal T-cell engraftment, a finding that has never been reported before. The presence of engrafted maternal T cells was misleading. Although ADA enzymatic levels were suggestive of ADA-SCID, the child did not present the classical signs of ADA deficiency; therefore, the initial diagnosis was of a conventional SCID. However, ADA toxic metabolites and molecular characterization confirmed this diagnosis. Polyethylene glycol-modified bovine (PEG) ADA therapy progressively decreased the number of maternal engrafted T cells. The child was grafted with full bone marrow from a matched unrelated donor, after a reduced conditioning regimen, and the result was the complete immunological reconstitution.

Chronic Granulomatous Disease in children: a single center experience.

Chronic Granulomatous Disease (CGD) is caused by the failure of the phagocytes to kill pathogens. We carried out a retrospective analysis of cellular, molecular and clinical features of 14 young patients (mean age at the onset of symptoms and diagnosis: 10 and 25months, respectively), 7 with autosomal recessive and 7 X-linked form, referred to the Children's Hospital of Brescia between 1999 and 2016. Two new mutations were found, one localized in the CYBB and one in the NCF1 genes. Twelve patients were followed in our institution; the average length of their follow-up after diagnosis was 66months in X-linked patients and 126months in autosomal recessive inheritance. The overall survival was 67%, 40% in X-linked and 86% in autosomal recessive form. Eight patients were treated with HSCT. We did not find a clear correlation between the clinical symptoms and the type of mutation, but the fine characterization of the patients was mandatory for therapeutic option, genetic counseling and prenatal diagnosis.

Bone Marrow Stroma and Vascular Contributions to Myeloma Bone Homing.

PURPOSE OF THE REVIEW: Herein we dissect mechanisms behind the dissemination of cancer cells from primary tumor site to the bone marrow, which are necessary for metastasis development, with a specific focus on multiple myeloma. RECENT FINDINGS: The ability of tumor cells to invade vessels and reach the systemic circulation is a fundamental process for metastasis development; however, the interaction between clonal cells and the surrounding microenvironment is equally important for supporting colonization, survival, and growth in the secondary sites of dissemination. The intrinsic propensity of tumor cells to recognize a favorable milieu where to establish secondary growth is the basis of the "seed and soil" theory. This theory assumes that certain tumor cells (the "seeds") have a specific affinity for the milieu of certain organs (the "soil"). Recent literature has highlighted the important contributions of the vascular niche to the hospitable "soil" within the bone marrow. In this review, we discuss the crucial role of stromal cells and endothelial cells in supporting primary growth, homing, and metastasis to the bone marrow, in the context of multiple myeloma, a plasma cell malignancy with the unique propensity to primarily grow and metastasize to the bone marrow.

Clinical Laboratory Automation: A Case Study.

BACKGROUND: This paper presents a case study of an automated clinical laboratory in a large urban academic teaching hospital in the North of Italy, the Spedali Civili in Brescia, where four laboratories were merged in a unique laboratory through the introduction of laboratory automation. MATERIALS AND METHODS: The analysis compares the preautomation situation and the new setting from a cost perspective, by considering direct and indirect costs. It also presents an analysis of the turnaround time (TAT). The study considers equipment, staff and indirect costs. RESULTS: The introduction of automation led to a slight increase in equipment costs which is highly compensated by a remarkable decrease in staff costs. Consequently, total costs decreased by 12.55%. The analysis of the TAT shows an improvement of nonemergency exams while emergency exams are still validated within the maximum time imposed by the hospital. CONCLUSIONS: The strategy adopted by the management, which was based on re-using the available equipment and staff when merging the pre-existing laboratories, has reached its goal: introducing automation while minimizing the costs.