Determinants of enhanced thromboxane biosynthesis in patients with systemic lupus erythematosus

OBJECTIVE: To evaluate the rate of thromboxane biosynthesis in patients with systemic lupus erythematosus (SLE), exploring the interplay between antiphospholipid antibodies (aPL) and 2 markers of endothelial perturbation: thrombin generation and platelet activation. METHODS: A comparison of 11-dehydrothromboxane B2 (TXB2) excretion, which is a marker of in vivo platelet activation, aPL, von Willebrand factor (vWF) and tissue plasminogen activator (tPA), which are 2 circulating markers of endothelial perturbation, and plasma levels of the prothrombin fragment F1+2, which is a marker of thrombin generation, was performed in 40 SLE patients and 40 healthy subjects. Thromboxane metabolite excretion was also measured in 8 SLE patients before and after treatment with low-dose aspirin. RESULTS: SLE patients had significantly higher 11-dehydro-TXB2 excretion, plasma F1+2, vWF, and tPA levels than controls. A statistically significant correlation was found between plasma levels of vWF and tPA and excretion of thromboxane metabolite. Moreover, significantly higher 11-dehydro-TXB2 was found in patients with aPL positivity and endothelial perturbation. Low-dose aspirin suppressed 11-dehydro-TXB2 by 80%, suggesting a predominant platelet source of enhanced thromboxane biosynthesis. After a median followup of 48 months, all SLE patients who experienced major cardiovascular events had thromboxane metabolite excretion, aPL positivity, and signs of endothelial perturbation. CONCLUSION: We have characterized a sensitive marker of platelet activation, which is abnormal in SLE patients who were positive for aPL and endothelial perturbation. This analytical approach may help identify those patients at increased risk of thrombosis as potential candidates for antiplatelet therapy.     

Wild carnivores as source of zoonotic helminths in north-eastern Italy

Summary Two hundreds and sixty red foxes, eighteen badgers and eight stone martens from north-eastern Italy were examined for zoonotic parasites by SCT, with particular attention to Trichinella sp. and Echinococcus multilocularis. No adult worms of E. multilocularis were observed in the intestine of red foxes or mustelids. Out of 223 fox faecal samples analysed by a commercial CA-ELISA, 5.8 % was positive to Echinococcus coproantigens. Trichinella sp. was detected by digestion of muscle in 1.2 % of examined foxes (2/172), but not in mustelids (0/11). Toxocara canis, responsible for human toxocarosis, resulted to be common in fox population (48.5 %). This parasite was found both in young (53.3 % of cubs and 61.9 % of sub-adults) and in adult animals (42.7 %). Other zoonotic parasites as Uncinaria stenocephala (52.3 %) and Trichuris vulpis (0.4 %) were detected in fox populations.     

Diagnosis of pulmonary amyloidosis by transbronchial biopsy

Previously reported cases of pulmonary parenchymal amyloidosis were diagnosed by open lung biopsy or postmortem examination. We describe 3 patients who were found to have amyloid deposits within the lung parenchyma by flexible fiberoptic bronchoscopy. In each case, the diagnosis was suspected when a waxy eosinophilic substance was observed within the alveolar walls of transbronchial biopsy specimens stained with hematoxylin-eosin. When stained with Congo red and examined under polarized light, this amorphous material exhibited the apple-green birefringence characteristic of amyloid fibrils. We suggest that a diagnosis of pulmonary amyloidosis can be made by transbronchial biopsy provided the appropriate histologic stains are employed. Special stains for amyloid should be obtained whenever histologic sections from transbronchial biopsy specimens reveal amorphous eosinophilic material within the alveolar septa or within the walls of small vessels.     

Aspirin and clopidogrel treatment impair nitric oxide biosynthesis by platelets

Aspirin and clopidogrel are used therapeutically for their anti-platelet effects. We examined the effects of aspirin and clopidogrel on basal and β-adrenoceptor (β-AR)-mediated platelet nitric oxide (NO) synthesis in healthy subjects and patients with coronary heart disease (CHD). Healthy subjects (n = 19) were randomized in a double-blind cross-over manner to receive aspirin or clopidogrel, each at 75 mg daily, for 14 days. Patients (n = 17) of similar age with CHD, taking aspirin, were randomized double-blind to either continue on aspirin 75 mg daily or to receive clopidogrel 75 mg daily for 14 days. NO synthase (NOS) activity was measured from l-[³H]arginine to l-[³H]citrulline conversion, and cGMP was determined by radioimmunoassay, in platelets basally and following incubation with isoproterenol or albuterol (each at 10⁻⁵ mol/L). In healthy subjects, aspirin did not affect basal NOS activity or cGMP in platelets, but suppressed the normal increase in both by isoproterenol and albuterol. Clopidogrel suppressed platelet NOS activity and cGMP both basally and in response to β-AR agonists. In platelets from CHD patients, clopidogrel suppressed basal and β-AR-stimulated NOS activity and cGMP as compared with aspirin. Platelet NOS activity and cGMP were lower in CHD subjects pre-randomization compared with healthy subjects both pre-randomization and post-aspirin. We conclude that chronic aspirin treatment suppresses β-AR-stimulated but not basal platelet NO synthesis, as previously described, whereas chronic clopidogrel treatment suppresses both, with resultant functional consequences. Moreover, CHD may itself be associated with decreased platelet NO biosynthesis.     

Prevalence of SARS-CoV-2 IgG antibodies in an area of northeastern Italy with a high incidence of COVID-19 cases: a population-based study

ObjectivesA seroprevalence study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was conducted in a high-incidence area located in northeastern Italy.MethodsAll citizens above 10 years of age resident in five municipalities of the Autonomous Province of Trento, with the highest incidence of coronavirus disease 2019 (COVID-19) cases, were invited to participate in the study. Among 6098 participants, 6075 sera and a standardized questionnaire administered face-to-face were collected between 5 May and 15 May 2020 and examined. Symptomatic individuals and their family contacts were tested by RT-PCR. Anti-SARS-CoV-2 antibodies were detected using an Abbott SARS-CoV-2 IgG assay, which was performed on the Abbott Architect i2000SR automated analyser. Seroprevalence was calculated as the proportion of positive results among the total number tested. A multivariable logistic regression model was performed to assess the relationship between seropositive versus seronegative individuals for a set of explanatory variables.ResultsA total of 1402 participants were positive for IgG antibodies against SARS-CoV-2, with a prevalence of 23.1% (1402/6075). The highest prevalence was found in the age class 40–49 years. Overall, 34.4% (2096/6098) of the participants reported at least one symptom. The ratio between reported cases identified by molecular test and those with seropositive results was 1:3, with a maximum ratio of about 1:7 in the age group <20 years and a minimum around 1:1 in those >70 years old. The infection fatality rate was 2.5% (35/1402). Among the symptoms, anosmia and ageusia were strongly associated with seropositivity.ConclusionsThe estimated seroprevalence of 23% was three-fold higher than the number of cases reported in the COVID-19 Integrated Surveillance data in the study area. This may be explained in part by a relatively high number of individuals presenting mild or no illness, especially those of younger age, and people who did not seek medical care or testing, but who may contribute to virus transmission in the community.     

Improved malignancy prediction by B3 breast lesions subclassification

Core-needle biopsy (CNB) of breast lesions can be classified into 5 categories according to lesion type and associated risk of malignancy. B3 category (lesion of uncertain malignant potential) constitutes a challenging problem in clinical decision, with most ending in excisional biopsy. Therefore, the aim of this study was to establish the incidence of malignancy on excision biopsy of B3 lesions and assess if subclassification (in B3a and B3b categories) according to the presence of atypia in otherwise B3 lesions better predicts malignancy on excision. Forty-eight cases with diagnosis of B3 lesion on CNB and matched surgical excision specimen were included to evaluate the positive predictive value (PPV) and odds for malignancy in CNB. All cases were further subclassified into B3a and B3b categories. B3 category lesions had an overall PPV for malignancy of 12.5% and significant low odds of malignancy of 0.14. When subclassified, B3b (lesions with atypia) demonstrated a higher PPV for malignancy (36.36%) with a nonsignificant odds. Inversely, B3a (lesions without atypia) demonstrated a PPV for malignancy of only 5.41% and a significant low odds of malignancy of only 0.06. The described low rate of malignancy in some of B3 lesions additionally reinforces the practice of avoiding surgical excision in selected patients and provides data that additionally support B3 lesion subclassification according to the presence of atypia. Subclassification of B3 category can further refine the current classification of associated risk of malignancy with possible implications in clinical management.