The humoral pattern recognition molecule PTX3 is a key component of innate immunity against urinary tract infection.

Immunity in the urinary tract has distinct and poorly understood pathophysiological characteristics and urinary tract infections (UTIs) are important causes of morbidity and mortality. We investigated the role of the soluble pattern recognition molecule pentraxin 3 (PTX3), a key component of the humoral arm of innate immunity, in UTIs. PTX3-deficient mice showed defective control of UTIs and exacerbated inflammation. Expression of PTX3 was induced in uroepithelial cells by uropathogenic Escherichia coli (UPEC) in a Toll-like receptor 4 (TLR4)- and MyD88-dependent manner. PTX3 enhanced UPEC phagocytosis and phagosome maturation by neutrophils. PTX3 was detected in urine of UTI patients and amounts correlated with disease severity. In cohorts of UTI-prone patients, PTX3 gene polymorphisms correlated with susceptibility to acute pyelonephritis and cystitis. These results suggest that PTX3 is an essential component of innate resistance against UTIs. Thus, the cellular and humoral arms of innate immunity exert complementary functions in mediating resistance against UTIs.

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.

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.

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.

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.

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.

Prognostic and diagnostic potential of local and circulating levels of pentraxin 3 in lung cancer patients.

There is a well-established link between inflammation and cancer of various organs, but little data are available on inflammation-associated markers of diagnostic and prognostic clinical utility in pulmonary malignancy. Blood samples were prospectively collected from 75 resectable lung cancer patients before surgery and in a cohort of 1,358 high-risk subjects. Serum levels of long pentraxin 3 (PTX3) were determined by high-sensitivity ELISA. PTX3 immunostaining was evaluated by immunohistochemistry in cancer tissue. Serum PTX3 levels in the high-risk population were not predictive of developing subsequent lung cancer or any other malignancy; however, serum PTX3 values in patients with lung cancer were significantly higher compared with cancer-free heavy smokers. With a cutoff of 4.5 ng/ml, specificity was 0.80, sensitivity 0.69, positive predictive value 0.15 and negative predictive value 0.98. The receiver operating curve (ROC) for serum PTX3 had an area under the curve (AUC) of 83.52%. Preoperative serum PTX3 levels in lung cancer patients did not correlate with patient outcome, but high interstitial expression of PTX3 in resected tumor specimens was a significant independent prognostic factor associated with shorter survival (p < 0.001). These results support the potential of serum PTX3 as a lung cancer biomarker in high-risk subjects. Furthermore, PTX3 immunohistochemistry findings support the role of local inflammatory mechanisms in determining clinical outcome and suggest that local expression of PTX3 may be of prognostic utility in lung cancer patients.

Metabolic Implications of Surgical Fat Removal: Increase of Adiponectin Plasma Levels After Reduction Mammaplasty and Abdominoplasty.

Recent studies tried to identify new indicators of risk in the development of insulin resistance, cardiovascular disease, and metabolic syndrome; recently, breast size has been proposed as a new measure of risk for type 2 diabetes mellitus in women. To understand the role of breast adipose tissue and subcutaneous adipose tissue in lipidic and glucose metabolism, we decided to evaluate the variation on levels of adiponectin in plasma and other well-known metabolic markers before and after surgical fat reduction.We formed 2 groups: breast reduction group (M-) and abdominoplasty group (ADD). For all patients enrolled in the study, we recorded anthropometric measurements 1 hour before surgery (that we considered as time zero). At time zero, we always performed a blood sample to observe the assay of glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, CRP, TNF-α, IL-1, IL-6, and adiponectin. The dosage of the above parameters was repeated 40 days after the surgical intervention with the aim of assessing whether they showed a statistically significant change after surgery.Adiponectin levels increased significantly in both groups of patients after surgery: in patients undergoing reduction mammaplasty and abdominoplasty, the mean increase was equal to 1.68 (P = 0.007) and 4.28 (P = 0.019), respectively. The variation in increase was not statistically different between the 2 groups (P = 0.254).Moreover, in the M- group, we observed that HDL levels increased and glycemia decreased significantly.Our study shows that reduction mammaplasty is a surgical procedure associated with a significant improvement in adiponectin level, HDL cholesterol level, and a significant decrease in glycemia level.The effective correlation between the role of breast adipose tissue and appearance of disease is still to be determined.

Elevations of inflammatory markers PTX3 and sST2 after resuscitation from cardiac arrest are associated with multiple organ dysfunction syndrome and early death.

BACKGROUND: A systemic inflammatory response is observed after cardiopulmonary resuscitation. We investigated two novel inflammatory markers, pentraxin 3 (PTX3) and soluble suppression of tumorigenicity 2 (sST2), in comparison with the classic high-sensitivity C-reactive protein (hsCRP), for prediction of early multiple organ dysfunction syndrome (MODS), early death, and long-term outcome after out-of-hospital cardiac arrest. METHODS: PTX3, sST2, and hsCRP were assayed at ICU admission and 48 h later in 278 patients. MODS was defined as the 24 h non-neurological Sequential Organ Failure Assessment (SOFA) score ≥ 12. Intensive care unit (ICU) death and 12-month Cerebral Performance Category (CPC) were evaluated. RESULTS: In total, 82% of patients survived to ICU discharge and 48% had favorable neurological outcome at 1 year (CPC 1 or 2). At ICU admission, median plasma levels of hsCRP (2.8 mg/L) were normal, while levels of PTX3 (19.1 ng/mL) and sST2 (117 ng/mL) were markedly elevated. PTX3 and sST2 were higher in patients who developed MODS (p<0.0001). Admission levels of PTX3 and sST2 were also higher in patients who died in ICU and in those with an unfavorable 12-month neurological outcome (p<0.01). Admission levels of PTX3 and sST2 were independently associated with subsequent MODS [OR: 1.717 (1.221-2.414) and 1.340, (1.001-1.792), respectively] and with ICU death [OR: 1.536 (1.078-2.187) and 1.452 (1.064-1.981), respectively]. At 48 h, only sST2 and hsCRP were independently associated with ICU death. CONCLUSIONS: Higher plasma levels of PTX3 and sST2, but not of hsCRP, at ICU admission were associated with higher risk of MODS and early death.

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.

Chyluria associated with nephrotic-range proteinuria: pathophysiology, clinical picture and therapeutic options.

Chyluria denotes the urinary excretion of chyle, which is a lymphatic fluid rich in chylomicrons. Chyle flows from the intestinal lacteals to the left subclavian vein through the thoracic duct. When an abnormal connection between these structures and the urinary tract develops, chyluria appears. The syndrome is often associated with a nephrotic-range proteinuria, and this could be a wrong indication to perform renal biopsy. Chyluria is classified as parasitic or nonparasitic, the former being induced by lymphatic filariasis, whereas the latter is caused by medical, traumatic or inherited diseases. The patient usually reports excretion of milky urines, monolateral flank pain, malnutrition, weight loss and weakness. Urinalysis demonstrates lymphocyturia associated with chylomicrons and triglycerides in the supernatant. The diagnostic approach is aimed to define the site of lymphourinary fistula. A selective ureteral catheterization allows to collect urine samples from each kidney, demonstrating a monolateral source of proteins and lipids and making renal biopsy superfluous. Other diagnostic tools include nuclear magnetic resonance urography and lymphoangiography. Many therapeutic options have been proposed. Sclerosing solution instillation into the renal pelvis and laparoscopic renal pedicle disconnection are the invasive procedures most commonly employed. Among the medical alternatives, a low-fat diet supplemented with medium-chain triglycerides is often followed by complete clinical and biochemical remission.

[Anti-Golgi antibodies: let me look around]. / Autoanticorpi anti-Golgi: anche l'occhio vuole la sua parte.

The new biotechnologies will be available a large number of diagnostic datas.The study of clinical cases with antibodies-anti-Golgi provides an opportunity to discuss the role of traditional approach by indirect immunofluorescence investigation.The strong collaboration between clinician and laboratory is the only possibility for a real progress.

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.

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.

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.

Gardnerella, Trichomonas vaginalis, Candida, Chlamydia trachomatis, Mycoplasma hominis and Ureaplasma urealyticum in the genital discharge of symptomatic fertile and asymptomatic infertile women.

This study aimed to establish the different prevalence of the microorganisms investigated in the two groups considered: fertile women with symptoms and asymptomatic women with infertility problems. The data from women (n= 952) investigated for two years for quality of genital discharge and the presence of Gardnerella vaginalis, Trichomonas vaginalis, Candida species, Streptococcus agalactiae, Mycoplasma hominis, Ureaplasma urealyiticum and Chlamydia trachomatis were retrospectively analyzed. In the population of fertile women with symptoms the microrganisms most frequently involved are Gardnerella vaginalis (26.6%), Candida species (12.1%) and Streptococcus agalactiae (9.2%). The genital discharges of asymptomatic women with infertility problems are characterized by a prevalence of Gardnerella vaginalis (19.7%), Enterobacteriaceae or Enterococci (12.1%) and Streptococcus agalactiae (8.6%). The reduction of vaginal lactobacilli flora and the presence of an elevated number of polymorphonucleates in the vaginal discharge are important parameters to consider for the evaluation of the health status of the human female urogenital tract. Our results indicate that is important to culture the vaginal discharge for Streptococcus agalactiae and for prevalence of Enterobacteriaceae and Enterococci. Lastly, the reasons for the prevalence of some microorganisms (Gardnerella vaginalis, Enterobacteriaceae and Enterococci, Streptococcus agalactiae) in the population of infertile asymptomatic women need to be better analyzed especially after the recent studies correlating idiopathic infertility with the presence of cervical cytokines in women with an abnormal vaginal flora.

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.

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.

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.