SARS-CoV-2 infection in patients with autoimmune rheumatic diseases in northeast Italy: A cross-sectional study on 916 patients.

BACKGROUND: Whether patients with autoimmune rheumatic diseases (ARD) have a higher risk for SARS-CoV-2 infection (COVID-19) and how SARS-CoV-2 pandemic impacts on adherence to therapy has not been fully elucidated. We assessed the rate and clinical presentation of COVID-19, and adherence to therapy in a large cohort of patients with ARD followed-up in a tertiary University-Hospital in Northeast Italy. METHODS: Between April 9th and April 25th, 2020, after SARS-CoV-2 infection peak, a telephone survey investigating the impact of COVID-19 on patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), ANCA-associated vasculitis (AAV), and idiopathic inflammatory myopathies (IIM) was administered. Demographics, disease activity status, therapy, occupational exposure, and adherence to social distancing advise were also collected. RESULTS: 916 patients (397 SLE, 182 AAV, 176 SSc, 111 RA, 50 IIM) completed the survey. 148 patients developed at least one symptom compatible with COVID-19 (cough 96, sore throat 64, fever 64, arthromyalgias 59, diarrhea 26, conjunctivitis 18, ageusia/hyposmia, 18). Among the 916 patients, 65 (7.1%) underwent SARS-CoV-2 nasopharyngeal swab (18 symptomatic and 47 asymptomatic), 2 (0.21%) tested positive, a proportion similar to that observed in the general population of the Veneto region. No deaths occurred. 31 patients (3.4%) withdrew ≥1 medication, mainly immunosuppressants or biologics. Adoption of social distancing was observed by 860 patients (93.9%), including 335 (36.6%) who adopted it before official lockdown. CONCLUSIONS: COVID-19 incidence seems to be similar in our cohort compared to the general population. Adherence to therapy and to social distancing advise was high.

The amount of cytokine-release defines different shades of Sars-Cov2 infection.

The recent outbreak of coronavirus disease (COVID 19), spreading from China all around the world in early 2020, has led scientists to investigate the immuno-mediated mechanisms underlying the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) infection. Depending on the amount of cytokines released as the result of the immunological activation induced by SARS-CoV2, three major clinical phenotypes can be identified: "mild",symbolized as a "drizzle" of cytokines, severe as a "storm", and critical as a "hurricane". In patients with mild symptoms, the release of pro-inflammatory cytokines is balanced to obtain a defense response against the virus which is often self-limiting and overcomes without tissue damage. In severe phenotype, resembling a "cytokine-release syndrome", SARS-CoV2 causes the lysis of the immune-mediators leading to a cytokine storm able to induce lung epithelium damage and acute respiratory distress syndrome. In critical patients, the immune response may become uncontrolled, thus the cytokine burst resembles a form of secondary hemophagocytic lymphohistiocytosis which may result in a multi organ failure. In addition to the standard of care, an immune-modulatory therapy tailored to each one of the different phenotypes should be used in order to prevent or reduce the release of cytokines responsible for organ damage and disease progression.

Diagnostic and prognostic role of renal histopathology in rheumatic diseases.

The objective was to evaluate renal involvement in several rheumatic diseases (i.e. rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, systemic sclerosis, systemic vasculitides). The method chosen was to define histopathological profiles reported in renal biopsies performed on patients with renal involvement due to different rheumatic diseases. Renal involvement observed in patients with rheumatic disease can be the direct result of the disease per se and/or a complication of drugs used in the disease treatment. The clinical-pathological correlations derived from the study of renal tissues can be useful for differential diagnosis, prognosis assessment and therapeutic decisions. Renal biopsy should be considered as an important tool for the management of nephropathies in patients with systemic rheumatic diseases.

Effect of training status on immune defence related gene expression in Thoroughbred: are genes ready for the sprint?

Athletic performance is both a stress factor and an adaptive response to exercise that may be modulated by training, reduce inflammation and help prevent disease. Studies on the endocrinology of exercise and training have demonstrated the existence of an integrated metabolic network of hormone and cytokine regulation. Subsequent molecular studies have shown that repeated bouts of exercise may establish new basal levels of gene expression at rest. The Thoroughbred horse may be a useful 'exercise model' for inter-individual comparisons between subjects with homogeneous genetic and environmental backgrounds and similar exercise management practices. In this study, the effects of training and acute effort on gene expression were evaluated with a real time PCR approach in athletic (n=10) and sedentary horses (n=9), using a previously characterised panel of genes known to be highly modulated during effort (CXCL2, TLR4, IL1ß, IL8, IL1RII, IL18, IL6 and CEBPß). A 'rest comparison' was performed to evaluate a training effect in both groups while a 'race comparison' was performed in athletic horses only (before, immediately after, and 12h after racing) to determine the effect of acute effort. The results indicated that many of the investigated genes (TLR4, IL1ß, IL1RII, IL18, IL6 and CEBPß) were expressed to a greater extent in athletic horses compared to sedentary animals when both were at rest. However, a time-course comparison in the athletic horses revealed that genes exhibiting the highest levels of expression at rest did not show significant changes after the race. The findings suggested that training may exert a conditioning on gene expression at rest leading to a more prompt response to exercise-induced stress in Thoroughbreds.

Isolation and characterization of ß-haemolytic-Streptococci from endometritis in mares.

The objective of this manuscript was to validate published PCR-based methods for detection of ß-haemolytic Streptococci by comparison with established bacteriological techniques using 85 clinical isolates recovered from uterine swabs of mares with clinical signs of endometritis and to determine the distribution of SeeL/SeeM and SzeL/SzeM superantigens in isolates of Streptococcus equi subsp. equi (S. equi) and S. equi subsp. zooepidemicus (S. zooepidemicus). The conventional bacteriological techniques showed the vast majority of these isolates (78) were S. zooepidemicus with just 5 Streptococcus dysgalactiae subsp. equisimilis (S. equisimilis) and 2 S. equi strains detected. The PCR analyses confirmed the bacteriological results demonstrating the reliability of the 16S rRNA PCR assay for detecting Streptococci, the multiplex PCR for differentiating between S. zooepidemicus, and S. equi, and PCR assays based on streptokinase genes for identification of S. equisimilis. PCRs for genes encoding superantigens revealed seeL and seeM specific amplicons with size of approximately 800 and 810 bp respectively for the S. equi strains and for 2 S. zooepidemicus strains. To our knowledge, this is the first report of szeL and szeM possession by S. zooepidemicus isolates derived from endometritis in mares.

Transcription of LINE-derived sequences in exercise-induced stress in horses.

A large proportion of mammalian genomes is represented by transposable elements (TE), most of them being long interspersed nuclear elements 1 (LINE-1 or L1). An increased expression of LINE-1 elements may play an important role in cellular stress-related conditions exerting drastic effects on the mammalian transcriptome. To understand the impact of TE on the known horse transcriptome, we masked the horse EST database, pointing out that the amount is consistent with other major vertebrates. A previously developed transcript-derived fragments (TDFs) dataset, deriving from exercise-stimulated horse peripheral blood mononuclear cells (PBMCs), was found to be enriched with L1 (26.8% in terms of bp). We investigated the involvement of TDFs in exercise-induced stress through bioinformatics and gene expression analysis. Results indicate that LINE-derived sequences are not only highly but also differentially expressed during physical effort, hinting at interesting scenarios in the regulation of gene expression in relation to exercise.

Genetic diversity in the Maremmano horse and its relationship with other European horse breeds.

The Maremmano is an Italian warmblood horse breed from central Italy. We characterized the genetic diversity and the degree of admixture in Maremmano in comparison to 14 other European horse breeds using 30 microsatellites. Between-breed diversity explained about 9 per cent of the total genetic diversity. Cluster analysis, genetic distances and genetic differentiation coefficients showed a close relationship of Maremmano with Hanoverian and Lusitano in accordance with breed history.

Microarray analysis after strenuous exercise in peripheral blood mononuclear cells of endurance horses.

It is known that moderate physical activity may have beneficial effects on health, whereas strenuous effort induces a state resembling inflammation. The molecular mechanisms underlying the cellular response to exercise remain unclear, although it is clear that the immune system plays a key role. It has been hypothesized that the physio-pathological condition that develops in athletes subjected to heavy training is caused by derangement of cellular immune regulation. The purpose of the present study was to obtain information on endurance horse gene transcription under strenuous conditions and to identify candidate genes causing immune system derangement. We performed a wide gene expression scan, using microarray technology, on peripheral blood mononuclear cells of ten horses chosen from high-level participants in national and international endurance races. The use of three different timepoints revealed changes in gene expression when post-effort samples (T1, taken immediately after the race; and T2, taken 24 h after the race) were compared with basal sample (T0, at rest). Statistical analysis showed no differences in gene expression between T0 and T2 samples, indicating complete restoration of homeostasis by 24 h after racing, whereas T1 showed strong modulation of expression, affecting 132 genes (97 upregulated, 35 downregulated). Ingenuity pathway analysis revealed that the main mechanisms and biofunctions involved were significantly associated with immunological and inflammatory responses. Real-time PCR was performed on 26 gene products to validate the array data.

[Endometrial ablation versus hysterectomy in women treated with tamoxifen]. / Ablazione endometriale versus isterectomia in pazienti in trattamento con tamoxifene.

AIM: The aim of our study is the assessment of the importance of the endometrial ablation versus hysterectomy in patients treated with tamoxifen for previous breast cancer. METHODS: Fifty-eight outpatients in therapy with tamoxifen for 1 year were controlled in the Department of Gynaecology of the University of Naples. We have selected these patients in two groups: group A, with 28 women with abnormal uterine bleeding and endometrial thickness >8 mm and group B, with 30 normal endometrium asymptomatic women. All patient of group A and 18 of group B were treated with endometrial ablation. RESULTS: Next follow-up showed normal hysteroscopy figures in 89% of cases and 5% of cases needed a hysterectomy for new abnormal uterine bleeding and cytology. CONCLUSION: Our results show the utility of endometrial ablation especially in selected cases in therapy with tamoxifen for previous breast cancer.

[Haemocoagulative modifications correlated with pregnancy]. / Modificazioni emocoagulative correlate allo stato gravidico.

AIM: The aim of this paper was to establish the physiologic changes in the coagulation and fibrinolytic systems during normal pregnancy. METHODS: One-hundred and twenty normal pregnant women were investigated in a longitudinal study involving 3 measurements: blood samples were collected at 12, 24 and 36 weeks of gestation and were assayed for prothrombin time, antithrombin III (ATIII) activity, protein C activity, protein S (PS) activity, prothrombin fragments 1+2, type 1 plasminogen activator inhibitor activity, tissue plasminogen activator antigen, plasminogen, activated protein C resistance, factors VII and VIII levels and D dimer. Student t-test, one way analysis of variance (ANOVA) and Fisher test were used for statistical analysis. RESULTS: Factor VII and factor VIII were always increased with respect to controls. Variance analysis showed a statistically significant reduction for anticoagulants (PS) and a rise for F1+2 and D dimer. With regard to fibrinolysis, there was an increase both for t-PA and PA1-1 during pregnancy. Moreover, the increased activity of factors of haemostasis was accompanied by an increase of activity and concentration of ATIII and acquired activated protein C resistance. CONCLUSIONS: These findings suggest that normal pregnancy is associated with an hypercoagulable state, resulting into a moderate risk for thrombosis during the different trimesters of pregnancy. Also broad spectrum assays which measure a range of trombin/fibrin formation in serum have become an established mean to identify activation of blood coagulation and/or fibrinolysis. There is a considerable interest in the application of these assays to the diagnosis of other acquired hypercoagulable states; such as thrombophilia during pregnancy. From the viewpoint of coagulation/fibrinolysis changes, the follow-up of thrombophilia markers could be recommended when levels of coagulation parameters exceed the normal values during pregnancy.

[Fetal and maternal amniocentesis complications]. / Complicanze materno fetali dell'amniocentesi.

AIM: The aim of this study was to estimate the incidence of complications due to the prenatal invasive diagnosis performed by amniocentesis at the Department of Prenatal Diagnosis of the Second University of Naples. METHODS: A total of 1.580 patients who underwent amniocentesis from January 2001 to December 2003, were submitted to a telephone interview concerning the complications that occurred after the invasive diagnosis. RESULTS: Only 1.416 patients out of the total patients interviewed answered correctly to the questionnaire. The complications that occurred in the first 24 h from amniocentesis (early complications) included light contractions and lipothymia respectively in 8.3% and 6.7% of cases; losses of amniotic fluid took place in 1.06% while bleedings were observed in 0.85% of cases. The incidence of abortions occurred in the week following amniocentesis was 0.78%. Preterm labor occurred in only 6% of the patients submitted to amniocentesis, spontaneous labor at term in 43% and cesarean section in 51%. The Apgar index at birth was normal in 95.7% of cases. In the remaining 4.3% pathologies like hypoglycemia or respiratory distress, which promptly regressed, were observed. Early complications and the incidence of abortions were significantly and independently associated with the double needle puncture but not with maternal age or the placenta specimen obtained during amniocentesis. CONCLUSIONS: A careful observation of the technique and the protocol, as well as a careful selection of patients are necessary presuppositions in order to further decrease the occurrence of complications due to amniocentesis.

The importance of Doppler ultrasonography in the management of fetal growth restriction.

AIM: To evaluate the importance of Doppler ultrasonography in fetuses in the management of fetal growth restriction (FGR). METHODS: Sixty-five pregnant women, aged between 23 to 39 years and from 27 to 37 weeks of pregnancy were selected; they all carried a single fetus showing a diminished growth curve in respect to the previous echographic examinations. Women affected with diabetes types I and II, renal pathologies and/or past endocrinopathies were excluded. All the patients with fetal growth restriction underwent accurate flussimetric mapping of some fetal districts such as umbilical artery and ductus venosus. Modalities of birth and the neonatal outcome were also considered. RESULTS: The patients selected were divided into 4 groups according to the velocimetrical data. The neonatal outcome was positive when the end diastolic flow was present in the umbilical artery associated with a normal flow in the ductus venosus. In cases where the end diastolic flow was absent in the umbilical artery, the management and neonatal outcome varied in relation to the morphology of the flow in the ductus venosus: the absence or reverse A phase of the mentioned flow is often indicative of acute fetal distress and unfavourable prognosis. Reverse end diastolic flow in the umbilical artery was always associated with the intrauterine death of the fetus. CONCLUSIONS: Our results confirm the validity of Doppler ultrasonography in the management and in the choice of timing for birth in cases of fetal growth restriction.

The incidence of chromosomal anomalies in fetuses affected by mild renal pyelectasis.

AIM: The aim of this study was to evaluate the clinical significance of borderline fetal pyelectasis, whether it is associated with chromosomal aberration or is the expression of a structural defect of the urinary tracts. METHODS: We carried out echographies on 2900 pregnant women in the 2nd trimester of their pregnancies between January 1998 and March 2002 at the Department of Obstetrics, Gynaecology and Neonatology. Any patient with fetuses affected by borderline pyelectasis in association with other echographic markers of aneuploidy and in women 35 years of age and older with fetuses presenting isolated pyelectasis underwent amniocentesis for karyotyping. RESULTS: We discovered 2.1% (62 cases) of borderline pyelectasis in the general population. The karyotype was normal in all cases of isolated pyelectasis; 3/5 of the fetuses with borderline renal pyelectasts associated with other risk factors showed a chromosomal aberration. CONCLUSION: In accordance with existing documentation, the results of our research confirmed that isolated borderline pyelectasis does not increase the risk of chromosomopathies; this latter is significantly more frequent when pyelectasis is present in older pregnant women (>35 years of age) or is associated with other sonographic markers of chromosomal anomalies (choroids plexus cysts, cystic hygroma etc.). Prenatal cytogenetic tests of the fetal karyotype are to be recommended in older mothers and/or in presence of associated echographic anomalies. In this study we propose an early diagnosis of mild forms of pyelectasis which are misdiagnosed by superficial echographies, but which can be associated with chromosomopathy.

The utility of fetal urine biochemistry in the management of lower urinary tract obstructions. A report of 3 cases.

The aim of this study is to implement the use of biochemical parameters in the analysis of fetal urine to assist with decision making for surgical intervention for fetal obstructive uropathy. Three patients were selected over a 6 month period following ultrasound diagnosis of megabladder and oligohydramnios. Amniocentesis and cystocentesis were performed for karyotyping and biochemical urinary electrolyte evaluation, respectively. Fetal urine biochemistry assisted in decision making with regard to patient and fetal well being. In each of the cases the parameter cutoffs were diagnostic of fetal condition. While the long term benefits of fetal intervention for obstructive uropathy are still debated, we feel that the use of urine biochemical criterIa provide the best current method to select the subjects to be submitted to vesicoamniotic shunt centres.

[Risk of chromosomal pathology in fetus with abnormal umbilical artery flowmetry]. / Rischio di cromosomopatie in feti con alterazioni flussimetriche dell'arteria ombelicale.

BACKGROUND: Goal of this study is to consider the incidence of chromosomal abnormalities in fetuses by velocimetry abnormalities. METHODS: The author select 64 pregnancies by velocimetry abnormalities of umbilical artery diastolic flow (ARED: Absent or Reverse end Diastolic Flow). RESULTS: The fetal cariotype from amniociti or from umbilical blood at delivery moment is resulted abnormal in 5 cases. Fetal-maternal risk factors of chromosomopaties are: malformations; fetal growth retardation; maternal age > or = 35. CONCLUSIONS: Other studies and other results are necessary for this discussion.

[Usefulness of ultrasonography of the cervical canal in the screening of pregnant women at risk of premature labor]. / Utilità dello studio ecografico del canale cervicale nello screening delle gestanti a rischio di parto pretermine.

BACKGROUND: Goal of the study is to evaluate the utility of cervical sonography in the second quarter as screening of pregnancies with risk of preterm labor. METHODS: A.A. evaluate, by transvaginal sonography (TVS) of the uterine cervix, 75 pregnancies with history of preterm labor and 25 with risk of preterm labor between XXIV and XXXIII week of pregnancy. The uterine cervix length < 40 mm and width > 5 mm, funneling were pathological and predictive factors of preterm labor. RESULTS: Eighty-five percent of pregnancies that have, at sonography TVG, abnormal values of length and width of uterine cervix, delivered before XXXVI week. CONCLUSIONS: These results confirm the importance of the high frequency ultrasonography transvaginal, TVS, for its predictive value and for treatment in pregnancies with risk of preterm labor.

[Prevention of gestational hypertension with calcium, linoleic acid, mono and polyunsaturated fatty acid supplements]. / Calcio, acido linoleico e acidi grassi mono e polinsaturi nella prevenzione della ipertensione gestazionale.

BACKGROUND: The aim of this study was to evaluate the benefits of calcium, linoleic acid and mono- and polyunsaturated fatty acids in the prevention of gestational hypertension. METHODS: Between January 1999 and June 2000, 65 primagravidas with a risk of gestational hypertension between the 20th and 24th week of pregnancy were recruited using Doppler velocimetry of the uterine arteries and Holter 24-h pressure monitoring. Patients with diabetes, hypertensive gestosis and previous renal pathologies were excluded. The patients were divided into 2 unequal groups: Group A (40 patients) was treated with calcium, linoleic acid, and mono and polyunsaturated fatty acid supplements; Group B (25 patients) received no treatment. The patients in both groups underwent Doppler velocimetry of the uterine arteries and Holter pressure monitoring at 28-30-32-35 weeks of gestation. RESULTS: Calcium linoleic acid and mono and polyunsaturated fatty acid supplements were effective in significantly reducing the incidence of gestational hypertension (p>0.05); in fact 90% of patients in Group A underwent a physiological evolution of pregnancy compared to only 10% affected by gestational hypertension. In the control group the incidence of this pathology was much higher (32%). CONCLUSIONS: The authors conclude that calcium linoleic acid and mono and polyunsaturated fatty acid supplements are useful and effective in the prevention of gestational hypertension in women at risk for this pathology.

The importance of high resolution transvaginal sonography in early screening of fetal chromosomal pathology.

BACKGROUND: Continuous technological improvement made in the field of ultrasound applied to obstetric diagnostics (see tridimensional sonography) has contributed to a better and non-invasive early diagnosis of fetal malformations. METHODS: To evaluate the usefulness of ultrasound in detecting early chromosomal derangements, the authors carried out a high resolution transvaginal sonography (> 6.5 mHz), between the 10th and 14th week of gestational age, on 650 pregnant women at risk for congenital anomalies and afterwards they were subjected to early amniocentesis RESULTS: Sonographic fetal anomalies were seen in 61 cases (9.3%). The incidence of fetal anomalies in these cases was 52.5%. Trisomies and number of sexual chromosome anomalies were seen, especially, in the cases of cystic septated hygroma and fetal nuchal translucency > or = 3 mm which are the most frequent sonographic markers of chromosomopathies. CONCLUSIONS: Although further studies are necessary, these findings suggest the usefulness of high resolution transvaginal sonography for the early screening of chromosomopathies.