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.

[Septic arthritis: what is the role for the rheumatologist?]. / Artrite settica: il ruolo del reumatologo.

Septic arthritis (SA) is a clinical emergency with considerable morbidity and mortality that can lead to rapid joint destruction and irreversible loss of function. The reported incidence varies from 2-5 cases per 100.000 individuals per year in the general populations to 70 cases per 100.000 individuals annually among patients with rheumatoid arthritis (RA). Predisposing factors are immunosuppressive and corticosteroids therapy and RA "itself". The expected decrease in incidence of SA was not seen over the last 20 years period but we can, on the contrary, expect an increase in the frequency of its appearance because of the population ageing, the increasingly prosthetic joint replacement, the ability of the bacteria to evade clearance by the host immune response and the rapidly growing number of patients with RA, ankylosing spondylitis and psoriatic arthritis treated with tumour necrosis factor alpha (TNF alpha) antagonists. Up to now there have been conflicting reports regarding joint infections in patients under anti-TNF therapy but according to data from Deutsch as well as the British register there might be an increase in the incidence of joint infections in anti-TNF treated patients. Microscopic analysis and culture of synovial fluid are fundamental diagnostic tools in the evaluation of possible joint sepsis. Sonographic guidance of arthrocentesis led to successful aspiration of difficult-to-access joints as shoulder and hip. There is controversy over which mode of drainage of septic synovial fluid should be employed but needle aspiration appear to be preferable to surgical treatment as an initial mode of treatment of SA. Rheumatologists should have a central role in the diagnosis and management of SA.

[Septic arthritis: a 12 years retrospective study in a rheumatological university clinic]. / Artriti settiche: studio retrospettivo di 12 anni in un unico centro reumatologico.

BACKGROUND: Septic arthritis is a disabling and potentially life-threatening condition that requires prompt diagnosis and treatment. The most important risk factors are joint prosthesis, pre-existing joint disease and immunosuppressive drugs. The aim of our study therefore was to revaluate all septic arthritis cases discharged from our Rheumatologic Unit in the last 12 years, to assess the risk factors, the clinical and laboratory characteristics, the causative microorganisms and its possible increase in frequency. METHODS: The medical records of 42 consecutive patients with septic arthritis discharged from our Rheumatology Unit between January 1995 and December 2006 were reviewed. The patients ranged in age from 23 to 90 and there isn't gender predominance. Septic arthritis was diagnosed based on the finding of purulent material in the joint space and/or the isolation of a bacterial pathogen from joint fluid. Demographic data, risk factors, co-morbidity, clinical manifestations, time interval between symptoms onset and diagnosis, treatment and laboratory data including serum white blood cell count, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), synovial white blood cells and culture results were analysed. We considered these parameters in the whole population and in two different age groups (< or =60, >60) and tried to determine if there was a change of microorganisms involved in septic arthritis during the years. RESULTS: Of 42 patients, 47% were aged 60 and younger. Only 10 patients were admitted to our unit before 2001. A predisposing factor was recorded in 90,5% of cases: 15 patients had rheumatoid arthritis, 8 were diabetic, 6 had seronegative arthritis, 4 had a connective tissue disease, 8 patients had a prosthetic infection and 3 were subjected recently to arthrocentesis. We found that patients aged 60 and younger were more frequently affected by joint disease and had a synovial white blood cell count lower than patients older than 60. Staphylococcus aureus caused septic arthritis in 70% of cases before 2001, and only in 35,8 % after 2001. Also, after 2001, some infections were caused by more unusual pathogens, prevalently in patients treated with TNFa inhibitors. Instead Streptococcus infections were found only in patients aged 70 and older. CONCLUSION: The incidence of bacterial arthritis has increased in the last six years and there was a modification of microorganisms involved, possibly related to a greater therapeutic aggressiveness. The increased frequency of joint disease and the use of immunosuppressive drugs in patients under the age of 60 could be responsible for a lower synovial white blood cell count in these patients.

[Italian Society of Rheumatology (SIR) recommendations for performing arthrocentesis]. / Raccomandazioni della Società Italiana di Reumatologia per l'esecuzione dell'artrocentesi.

Joint fluid aspiration, or arthrocentesis, is one of the most useful and commonly performed procedures for the diagnosis and treatment of rheumatic diseases, but to date no definite guidelines have been published. For this reason, a group of experts of the Italian Society of Rheumatology (SIR) produced evidence based recommendations for performing arthrocentesis. Among them, the most relevant are: a) arthrocentesis is necessary when synovial effusion of unknown origin is present, especially if septic or crystal arthritis is suspected; b) the patient should be clearly informed of the benefits and risks of the procedure in order to give an informed consent; c) ultrasonography should be used to facilitate arthrocentesis in difficult joints; d) fluid evacuation often has a therapeutic effect and facilitates the success of the following intraarticular injection; e) careful skin disinfection and the use of sterile, disposable material is mandatory for avoiding septic complications. Disposable, non sterile gloves should always be used by the operator, mainly for his own protection; f) contraindications are the presence of skin lesions or infections in the area of the puncture; g) the patient's anticoagulant treatment is not a contraindication, providing the therapeutic range is not exceeded; h) joint rest after arthrocentesis is not indicated. Several of these recommendations were based on experts' opinion rather than on published evidence which is scanty.

Ionizing radiations in pregnancy and teratogenesis: a review of literature.

The present paper is a review of the data available in the literature concerning the prenatal exposure to radiation evaluating the reported teratogenic effect. We have particularly focused on the fetal effects of maternal ionising radiation exposure, both diagnostic and occupational, particularly in terms of congenital anomalies and birth weight. Ionising radiation represents a possible teratogen for the fetus, but this risk has been found to be dependent on the dosage and the effects correlatable to the gestational age at exposure. Recently, of particularly note is the fact that maternal thyroid exposure to diagnostic radiation has been associated with a slight reduction in the birth weight. Inadvertent exposure from diagnostic procedures in pregnancy doesn't usually increase the natural risk of congenital anomalies but creates a considerable state of maternal anxiety. Diagnostic radiological procedures should be avoided in pregnant women unless the information cannot be obtained by other techniques.

Charcot-Marie-Tooth disease type I and related demyelinating neuropathies: Mutation analysis in a large cohort of Italian families.

Charcot-Marie-Tooth neuropathy type 1 (CMT1), the most common hereditary neurological disorder in humans, is characterized by clinical and genetic heterogeneity. It is caused mainly by a 1.5 Mb duplication in 17p11.2, but also by mutations in the myelin genes PMP22 (peripheral myelin protein 22), MPZ (myelin protein zero), Cx32 (connexin 32; also called GJB1), and EGR2 (early growth response 2). In this study, we have screened 172 index cases of Italian families in which there was at least one subject with a CMT1 diagnosis for the duplication on 17p11.2 and mutations in these genes. Among 170 informative unrelated patients, the overall duplication frequency was 57.6%. A difference could be observed between the duplication frequency in familial cases (71.6%) and that observed in non-familial cases (36.8%). Among the non-duplicated patients, 12 were mutated in Cx32, four in MPZ, two in PMP22, and none in the EGR2. In the non-duplicated cases, the overall point mutation frequency for these genes was 25.0%. We describe the mutations identified, and consider possible genotype-phenotype correlation.

Morphologic study of microcirculation in acromegaly by capillaroscopy.

Although wide range investigations on the heart and great vessels have been reported in acromegaly, the field of microcirculation is still largely vacant. The nailfold is a window through which we can observe in vivo the vascular bed. This study investigates through nailfold capillaroscopy the morphology of cutaneous microcirculation in acromegaly in relationship with the usual hormonal parameters of disease activity. Twenty-five acromegalic patients and 26 normal subjects, age and sex matched, were studied. A subgroup of acromegalics (8 patients) was considered in stable remission, and the remaining 17 had active disease. Capillaroscopy was performed in each subject by in vivo computer aided stereomicroscopy (magnification, x400). The following morphological parameters were calculated: the number of tortuous loops, meandering capillaries, and capillaries per millimeter; avascular areas; visibility of subpapillary plexus; the capillary length; and intercapillary distance. We were unable to perform the exam in 4 of 25 patients because visibility was poor. The capillary number and length were significantly reduced in acromegalics compared to controls [8.9 +/- 1.5 vs. 10.3 +/- 1.2 no./mm (P = 0.0010) and 174 +/- 49 vs. 255 +/- 24 microm (P < 0.0001)]. Moreover, in acromegalics, the numbers of tortuous loops and meandering capillaries were significantly increased [19 +/- 8 vs. 13 +/- 5 (P = 0.0027) and 10 +/- 12 vs. 0.7 +/- 1.1 (P < 0.0001)]. The capillaroscopic alterations were still observed in a smaller group of 8 nondiabetic and nonhypertensive acromegalics. We found branch-like capillaries in 4 acromegalic patients, but not in the control group. Finally, we observed a meaningful different and ameliorated capillaroscopic morphology in acromegalic patients in stable remission compared to active disease patients as far as the total number (density) and meandering capillaries were concerned. In conclusion, our study shows that in acromegaly, morphological alterations also affect the peripheral microcirculation, which seems to be influenced by the activity of the disease. We believe that nailfold capillaroscopy may represent an additional useful tool in the follow-up of acromegalic patients.

Estimation of the mutation frequencies in Charcot-Marie-Tooth disease type 1 and hereditary neuropathy with liability to pressure palsies: a European collaborative study.

A European collaboration on Charcot-Marie-Tooth type 1 (CMT1) disease and hereditary neuropathy with liability to pressure palsies (HNPP) was established to estimate the duplication and deletion frequency, respectively, on chromosome 17p11.2 and to make an inventory of mutations in the myelin genes, peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ) and connexin 32 (Cx32) located on chromosomes 17p11.2, 1q21-q23 and Xq13.1, respectively. In 70.7% of 819 unrelated CMT1 patients, the 17p11.2 duplication was present. In 84.0% of 156 unrelated HNPP patients, the 17p11.2 deletion was present. In the nonduplicated CMT1 patients, several different mutations were identified in the myelin genes PMP22, MPZ and Cx32.

Hereditary spastic paraplegia associated with peripheral neuropathy: a distinct clinical and genetic entity.

Hereditary motor and sensory neuropathy type V is a very rare disease in which hereditary spastic paraplegia is associated with peripheral motor and sensory neuropathy. The symptomatic onset of the disorder is usually in the second decade of life or later and the course is progressive over many years. Hereditary motor and sensory neuropathy type V is inherited as an autosomal dominant trait usually showing incomplete penetrance. So far, no molecular data are available in the literature about this disease. In our study we present clinical and molecular data from a large Italian family displaying hereditary motor and sensory neuropathy type V. Taking into account the clinical features in this family, we have performed a linkage analysis for markers strictly associated with all the known loci for autosomal dominant and autosomal recessive forms of hereditary spastic paraplegia and hereditary motor and sensory neuropathy type II, and have found no linkage to these loci. Our study suggests that hereditary motor and sensory neuropathy type V is not only a distinct clinical entity but also a distinct genetic entity.

Protective effect of superoxide dismutase and polyethylene glycol-linked superoxide dismutase against renal warm ischemia/reperfusion injury.

The protective effect of oxygen free radical scavenger superoxide dismutase (SOD) against the warm ischemic damage that occurs in kidneys harvested from non-heart-beating donors is controversial because of its short half-life. In this model, we compared the protective effect of SOD and two longer lasting polyethylene glycol (PEG)-linked forms of SOD in a model of renal ischemia induced by 60 min of arterial clamping in rats. Rats treated with PEG1-SOD and PEG2-SOD had a better renal function than controls, with significantly lower serum creatinine levels throughout the follow-up period and a significantly higher creatinine clearance on postoperative days 1, 2, and 4. In native SOD treated-rats, serum creatinine was lower than in controls, though not significantly so, and creatinine clearance was significantly higher on postoperative day 4. Our results indicate that the protective effect of SOD against renal warm ischemia can be enhanced by prolonging its half-life by binding the enzyme to PEG.

The influence of intra-articular hyaluronic acid on PGE2 and cAMP of synovial fluid.

Prostaglandin (PG)E2, cyclic adenosine monophosphate (cAMP), white blood cells (WBC), total protein (TP), total complement activity (CH50) and beta-2-microglobulin (beta-2-m) were measured at baseline and after eight days in the synovial fluid (SF) of 16 patients affected with knee-joint effusion due to various arthropathies. The volume of SF was also calculated. Eight patients--4 with rheumatoid arthritis (RA), 2 with recurrent monoarthritis (RM) and 2 with osteoarthritis (OA) were randomly allocated to the treatment with intra-articular injection of Hyalgan (HA, Na-hyaluronate, 20 mg/2 ml), while eight patients having similar arthropathies--4 RA, 2 RM and 2 OA--were not treated (control group). In the patients treated with HA a significant reduction of SF volume (from 28.5 +/- 5.1 ml to 20.5 +/- 4.0 ml; p less than 0.02) and PGE2 (from 96.1 +/- 22.7 pg/ml to 66.2 +/- 14.5 pg/ml; p less than 0.05) was found, whereas cAMP concentration was significantly increased (from 4.5 +/- 0.7 pmol/ml to 7.2 +/- 1.2 pmol/ml; p less than 0.05). No significant variations were observed in the control group. Moreover, no differences in WBC count, TP and beta-2-m and CH50 were found in either group. These data could suggest an anti-inflammatory effect of HA that appears to be mediated by PG-inhibition as well as cAMP stimulation.

PEG-modified glucose oxidase immobilized on a PVA cryogel membrane for amperometric biosensor applications.

Poly(ethylene glycol)-modified glucose oxidase was immobilized in a poly(vinyl alcohol) cryogel membrane, obtained by a freezing-thawing cyclic process, to obtain a suitable amperometric glucose sensor. The covalent linkage between PEG and GOD molecule improved the physical immobilization of enzyme in the polymeric matrix, by decreasing its loss in time. Sensor behaviour was evaluated electrochemically with a hydrogen peroxide electrode. The glucose content in standard solutions was determined and linear calibration curves in the 5x10(-5)-5x10(-3) mol l(-1) range were obtained. The kinetic parameters in the immobilized system were evaluated and analytical characteristics of sensor, including stability and influence of pH and temperature, were determined.

Anti-thyroid microsomal antibody in synovial fluid as a revealing feature of seronegative autoimmune thyroiditis.

Two cases of recurrent monoarthritis are described in which antithyroid microsomal (antiMi) autoantibody (Ab) was found in synovial fluid (SF) before any clinical or serological evidence of thyroid disease. Subsequently, the follow-up of the two patients showed the appearance of thyroiditis within 2-5 years. The presence of anti-Mi Ab in SF might anticipate the appearance of autoimmune thyroiditis even in the absence of serum detectable antithyroid Ab, as was later observed in these two cases.

Effect of sludge-amendment or nutrient addition on the biodegradation of the herbicide isoproturon in soil.

Adding sludge to agricultural soil results in added organic matter, nutrients and metallic and/or organic pollutants. These components may modify the behaviour of pesticides in the soil. We monitored possible changes in the degradation of the herbicide isoproturon (production of CO2 and degradation products) in soil amended with sludge, heavy metals or nitrogen and phosphorus. The treated and control soils were incubated under controlled conditions for 60 days. The nitrogen and phosphorus had the greatest effect on isoproturon degradation, independent of the presence of pollutants. Mineralisation of the herbicide to CO2 was slow and seemed to be linked to a fast degradation and to the accumulation of a complex degradation product that was neither catabolized nor adsorbed, 4,4'-diisopropylazobenzene. This degradation pathway also produced smaller amounts of non-extractable residues. Sewage sludge had no significant effect on isoproturon degradation, despite a large increase of organic matter mineralisation (factor 2).

Pegylated enzyme entrapped in poly(vinyl alcohol) hydrogel for biocatalytic application.

A procedure for enzyme entrapment into matrices suitable for biocatalytic applications is reported. The method, which takes advantage of the stable formation of polyvinyl alcohol (PVA) hydrogels by freezing and thawing PVA aqueous solutions, was assayed using lipase as model enzyme. The leakage of lipase was minimised by using high molecular weight PVA and by previous conjugation of the enzyme to PEG. The immobilised PEG enzyme maintained its catalytic activity in organic solvents also, thus allowing enzymatic activity towards water insoluble substrates. The activity was largely increased reducing the diffusional constrain by cutting the matrices into slices of micron size. Matrix-entrapped lipase-PEG, when used in the hydrolysis of acetoxycoumarins, showed a conversion rate of about 10 times lower than the enzyme-PEG in the free form, and maintained regioselectivity when a diacetylated product was used as substrate.

Cost-benefit evaluation of HRCT.

HRCT permits visualization of the secondary pulmonary lobule. The technique of HRCT, and the anatomy of the lung structure are discussed. The patterns and distribution of disease, and diagnosis of many diffuse lung diseases are also discussed. Finally biological, economic and clinical aspects of HRCT are evaluated: a) the dose administered is comparable with the dose administered with chest radiography; b) HRCT examination does not cost more than CT examination (about 100 dollars); c) HRCT is useful in the detection, evaluation and diagnosis of diffuse lung diseases, such as acute or chronic interstitial disease, emphysema and bronchiectasis, both in paediatric, adult and elderly patients.

[The diabetic hand]. / La mano diabetica.

Diabetes mellitus is a chronic metabolic condition characterized by persistent hyperglycaemia with resultant morbidity and mortality related to its microvascular and macrovascular complications. In addition diabetes is also associated with several musculoskeletal disorders of the hand, that can be debilitating. There is increased incidence of these abnormalities in patients with type 1 and type 2 diabetes compared with the general population, related to disease duration but not to the age or sex. Typical diabetes associated hand condition include the palmar flexor tenosynovitis, Dupuytren's contracture, syndrome of limited joint mobility, carpal tunnel syndrome, Charcot arthropathy and reflex sympathetic dystrophy. Maintaining good glycaemic control by exercise, diet and drugs improves or prevents the development of these hand rheumatic condition. In this brief report we review the rational therapeutic approach to these disorders.

[Post-traumatic arthritis in a patient with Jadassohn's anetoderma]. / Artrite post-traumatica in paziente con anetodermia di Jadassohn.

We describe the emergence of arthritis following a physical trauma, in a young man with clinical and histopathologic features of primary anetoderma (Jadassohn type) of 13 years' duration. Diagnosis of post-traumatic arthritis in a young patient with genetic predisposition was assumed. Indeed septic arthritis and other possible cause of arthritis were ruled out.

[Frequency of the bleeding risk in patients receiving warfarin submitted to arthrocentesis of the knee]. / Frequenza del rischio emorragico nei pazienti in trattamento con warfarin sottoposti ad artrocentesi del ginocchio.

OBJECTIVE: To evaluate the potential bleeding risks of arthrocentesis in patients with different arthropathies and taking oral anticoagulants. MATERIALS AND METHODS: Fifteen consecutive patients, 8 males and 7 females, treated with anticoagulant therapy for atrial fibrillation (9 pts), deep venous thrombosis (4 pts) and replacement of cardiac valves (3 pts) were submitted to arthrocentesis for synovial fluid effusion due to different arthropathies. In all patients INR was

[Paget's disease of bone associated with autoimmune thyroiditis and joint chondrocalcinosis]. / Maladie osseuse de Paget associée à une thyroïdite auto-immune et à une chondrocalcinose articulaire.

A case of scapular Paget's disease of bone with concurrent autoimmune thyroiditis and articular chondrocalcinosis is reported. Although infrequent, this combination suggests the involvement of common pathogenic mechanisms: thyroiditis and Paget's disease may stem from the same viral infection and/or autoimmune disorder, whereas chondrocalcinosis may be the consequence of thyroiditis-related hypothyroidism. In contrast, the association of Paget's disease and chondrocalcinosis may be fortuitous, since both disorders are common.