Role of placental inflammatory mediators and growth factors in patients with rheumatic diseases with a focus on systemic sclerosis

Objectives: Pregnancy in SSc is burdened with an increased risk of obstetric complications. Little is known about the underlying placental alterations. This study aimed to better understand pathological changes and the role of inflammation in SSc placentas. Leucocyte infiltration, inflammatory mediators and atypical chemokine receptor 2 (ACKR2) expression in SSc placentas were compared with those in other rheumatic diseases (ORD) and healthy controls (HC). Methods: A case–control study was conducted on eight pregnant SSc patients compared with 16 patients with ORD and 16 HC matched for gestational age. Clinical data were collected. Placentas were obtained for histopathological analysis and immunohistochemistry (CD3, CD20, CD11c, CD68, ACKR2). Samples from four SSc, eight ORD and eight HC were analysed by qPCR for ACKR2 expression and by multiplex assay for cytokines, chemokines and growth factors involved in angiogenesis and inflammation. Results: The number of placental CD3, CD68 and CD11 cells was significantly higher in patients affected by rheumatic diseases (SSc+ORD) compared with HC. Hepatocyte growth factor was significantly increased in the group of rheumatic diseases patients (SSc+ORD) compared with HC, while chemokine (C-C motif) ligand 5 (CCL5) was significantly higher in SSc patients compared with ORD and HC. CCL5 levels directly correlated with the number of all local inflammatory cells and higher levels were associated with histological villitis. Conclusions: Inflammatory alterations characterize placentas from rheumatic disease patients and could predispose to obstetric complications in these subjects

The impact of unrecognized autoimmune rheumatic diseases on the incidence of preeclampsia and fetal growth restriction: A longitudinal cohort study

BACKGROUND: The burden of pregnancy complications associated with well defined, already established systemic rheumatic diseases preexisting pregnancy such as rheumatoid arthritis, systemic lupus erythematosus or scleroderma is well known. Systemic rheumatic diseases are characterized by a long natural history with few symptoms, an undifferentiated picture or a remitting course making difficult a timely diagnosis. It has been suggested that screening measures for these diseases could be useful but the impact of unrecognized systemic rheumatic disorders on pregnancy outcome is unknown. The objective of the study was to evaluate the impact of previously unrecognized systemic autoimmune rheumatic on the incidence of preeclampsia and fetal growth restriction (FGR). METHODS: A longitudinal cohort-study with enrolment during the first trimester of pregnancy of women attending routine antenatal care using a two-step approach with a self-reported questionnaire, autoantibody detection and clinical evaluation of antibody-positive subjects. The incidence of FGR and preeclampsia in subjects with newly diagnosed rheumatic diseases was compared to that of selected negative controls adjusting for potential confounders by logistic regression analysis. RESULTS: The prevalence of previously unrecognized systemic rheumatic diseases was 0.4 % for rheumatoid arthritis (19/5232), 0.25 % (13/5232) for systemic lupus erythematosus, 0.31 % (16/5232) for Sj\uf6gren's syndrome, 0.3 % for primary antiphospholipid syndrome (14/5232) and 0.11 % (6/5232) for other miscellaneous diseases. Undifferentiated connective tissue disease was diagnosed in an additional 131 subjects (2.5 %). The incidence of either FGR or preeclampsia was 6.1 % (36/594) among controls and 25.3 % (50/198) in subjects with unrecognized rheumatic diseases (excess incidence\u2009=\u20093.9 % (95 % CI\u2009=\u20092.6-9.6) or 34 % (95 % CI\u2009=\u200922-44) of all cases of FGR/preeclampsia). The incidence of small for gestational age infant (SGA) was higher among subjects with unrecognized rheumatic diseases (41/198 as compared to 46/594; adjOdds Ratio\u2009=\u20093.1, 95 % CI =1.96-4.95) than in controls. The excess incidence associated with unrecognized rheumatic diseases was 2.7 % (95 % CI\u2009=\u20091.5-4) or 25 % (95 % CI\u2009=\u200912.8-34.8) of all SGA cases. CONCLUSIONS: Unrecognized autoimmune systemic rheumatic disorders are associated with a significant proportion of preeclampsia and fetal growth failure, suggesting that their role in the etiology of adverse pregnancy outcome is probably undervalued

The effect of newly diagnosed undifferentiated connective tissue disease on pregnancy outcome

OBJECTIVE: The purpose of this study was to evaluate pregnancy outcome in a cohort of patients with newly diagnosed undifferentiated connective tissue disease (UCTD). STUDY DESIGN: We conducted a nested case-control study that compared 41 patients who had early UCTD that was diagnosed at 11-14 weeks of pregnancy with 82 healthy control subjects. RESULTS: During pregnancy, UCTD progressed to a definite connective tissue disease in 2 of 41 patients (4.9%). Sixteen of the 41 patients (39%) with UCTD tested positive for anti-Ro (SSA) antibodies. Compared with the control subjects, the women with UCTD had higher rates of small for gestational age (SGA; 12/40 vs 11/80; P = .05). The rate of complications of pregnancy (preterm delivery at </= 37 weeks of gestation, SGA, preeclampsia, late fetal loss) was 39% (16/41) among cases and 13.4% (11/82) in control subjects (adjusted odds ratio, 3.98; 95% CI, 1.59-9.49). CONCLUSION: Pregnant patients with UCTD are at increased risk of SGA and complications of pregnancy

The dangers of dental devices as reported in the Food and Drug Administration Manufacturer and User Facility Device Experience Database.

BackgroundThe authors conducted a study to determine the frequency and type of adverse events (AEs) associated with dental devices reported to the Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE) database.MethodsThe authors downloaded and reviewed the dental device-related AEs reported to MAUDE from January 1, 1996, through December 31,2011.ResultsMAUDE received a total of 1,978,056 reports between January 1, 1996, and December 31, 2011. Among these reports, 28,046 (1.4%) AE reports were associated with dental devices. Within the dental AE reports that had event type information, 17,261 reported injuries, 7,777 reported device malfunctions, and 66 reported deaths. Among the 66 entries classified as death reports, 52 reported a death in the description; the remaining were either misclassified or lacked sufficient information in the report to determine whether a death had occurred. Of the dental device-associated AEs, 53.5% pertained to endosseous implants.ConclusionsA plethora of devices are used in dental care. To achieve Element 1 of Agency for Healthcare Research and Quality's Patient Safety Initiative, clinicians and researchers must be able to monitor the safety of dental devices. Although MAUDE was identified by the authors as essentially the sole source of this valuable information on adverse events, their investigations led them to conclude that MAUDE had substantial limitations that prevent it from being the broad-based patient safety sentinel the profession requires.Practical implicationsAs potential contributors to MAUDE, dental care teams play a key role in improving the profession's access to information about the safety of dental devices

Apheresis in high risk antiphospholipid syndrome pregnancy and autoimmune congenital heart block

In the first part a prospective cohort study was reported to evaluate the efficacy and safety of a treatment protocol including plasma exchange (PE) or PE plus intravenous immunoglobulins (IVIG) or immunoadsorption (IA) plus IVIG administered in addition to conventional therapy to 22 pregnant women with high-risk APS. The results indicate that PE or IA treatments administered along with IVIG and conventional antithrombotic therapy could be a valuable and safe therapeutic option in pregnant APS women with triple antiphospholipid antibody positivity along with a history of thrombosis and/or one or more severe pregnancy complications. In the second part the efficacy and safety of PE combined with IVIG and steroids were evaluated for the treatment of 10 patients with autoimmune congenital heart block (CHB) by comparing maternal features, pregnancy outcome and side effects with those of 24 CHB patients treated with steroids only. The patients treated with the combined therapy showed a statistically significant regression of 2nd degree blocks, an increase in heart rate at birth and a significantly lower prevalence of pacing in the first year of life. Moreover, no side effects were observed except for a few steroid-related events. If these results are confirmed by large-scale studies, the apheretic procedures could lead to improved outcomes in the treatment of these devastating diseases

Psychosocial burden in young patients with primary anti-phospholipid syndrome: an Italian nationwide survey (The AQUEOUS study)

The AQUEOUS (Anti-phospholipid syndrome: a QUEstionnaire for yOUng patientS) study aimed to assess how the diagnosis of primary anti-phospholipid syndrome (PAPS) affects the psychosocial status of young patients