The Risk of Obstetric Complications and the Effects of Treatment in Women with Low Titer and Medium-High Titer Anti-Phospholipid Antibodies

Background/Purpose: The association of low titer anti-phospholipid antibodies (aPL) with obstetric anti-phospholipid syndrome (APS) is increasingly acknowledged, even though some studies have showed conflicting results. To raise further evidence on the relevance of low titer aPL in pregnancy morbidity (PM), we retrospectively reviewed the clinical records of pregnant women attending a joint obstetric/rheumatology clinic over the years 2009-2016. Methods: Patients were included when positive in at least one criteria aPL assay, at any titer, in two occasions minimum 12 weeks apart. Statistical analysis was performed using R package. Results: 111 women (338 pregnancies) were identified. 51 women displayed low-titer aPL, with 160 pregnancies. 60 patients carried aPL at medium-high titers, with 178 pregnancies. 4 patients (4%) had thrombotic APS, 27 (24%) obstetric APS, 7 (6%) thrombotic and obstetric APS, 15 (14%) medium-high titer aPL and non criteria PM, 7 (6%) medium-high titer aPL and no PM, 18 (16%) low titer aPL and non criteria PM and 15 (14%) low titer aPL and no PM. Low-titer aPL were significantly associated with pregnancy complications (c2=8.82, p=0.003). Considering 245 untreated pregnancies, a significant difference in PM distribution was noted for low titer and medium-high titer aPL (p=0.003, Table 1). Among patients with low titer aPL, treatment with low molecular weight heparin [LMWH] + low-dose aspirin [LDASA] significantly improved pregnancy outcomes (p<<0.001, odds ratio [OR]=0.07, 95% CI=0.007\u20130.300), leading to a 14.3-fold reduction of obstetric complications. Hydroxychloroquine [HCQ] was not associated with a significant improvement in live birth rate (p=0.079). Among women with medium-high titer aPL, the standard therapeutic approach with LMWH+LDASA resulted in a significant improvement of obstetric outcome (p<<0.001, OR=0.20, 95% CI=0.100\u20130.400). HCQ treatment significantly improved obstetric outcome, carrying a 3-fold increase in the live birth rate (p=0.025, OR=0.34, 95% CI=0.117\u20130.894). Conclusion: According to our data, low titer aPL are significantly associated with aPL-associated obstetric complications, with a lower prevalence of premature birth compared to medium-high titer aPL. Treatment with LDASA+LMWH led to a higher increase of live birth rate in women with low titer aPL compared to those with medium-high titer aPL. Additional treatment such as HCQ were effective in women with medium-high titer aPL but not those with low titer aPL. Table 1. Obstetric outcomes (defined according to Miyakis et al, 2006) in 245 untreated pregnancies in women with low titer and medium-high titer anti-phospholipid antibodies

Providing high-quality care remotely to patients with rare bone diseases during COVID-19 pandemic

During the COVID-19 outbreak, the European Reference Network on Rare Bone Diseases (ERN BOND) coordination team and Italian rare bone diseases healthcare professionals created the "COVID-19 Helpline for Rare Bone Diseases" in an attempt to provide high-quality information and expertise on rare bone diseases remotely to patients and healthcare professionals. The present position statement describes the key characteristics of the Helpline initiative, along with the main aspects and topics that recurrently emerged as central for rare bone diseases patients and professionals. The main topics highlighted are general recommendations, pulmonary complications, drug treatment, trauma, pregnancy, children and elderly people, and patient associations role. The successful experience of the "COVID-19 Helpline for Rare Bone Diseases" launched in Italy could serve as a primer of gold-standard remote care for rare bone diseases for the other European countries and globally. Furthermore, similar COVID-19 helplines could be considered and applied for other rare diseases in order to implement remote patients' care

Corrigendum to: Comparative study of obstetric antiphospholipid syndrome (OAPS) and non-criteria obstetric APS (NC-OAPS): report of 1640 cases from EUROAPS registry

Rheumatology 2020;59:1306–1314. doi:https://doi.org/10.1093/rheumatology/kez419 In the original article, the affiliation of co-author Cecilia Beatrice Chighizola should have read: “Experimental Laboratory of Immunological and Rheumatologic Researches, Istituto Auxologico Italiano, IRCCS, Cusano Milanino, Milan, Italy”. These details have been corrected only in this corrigendum to preserve the published version of record

Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in ∼40% of patients

Mosquito-borne West Nile virus (WNV) infection is benign in most individuals but can cause encephalitis in <1% of infected individuals. We show that ∼35% of patients hospitalized for WNV disease (WNVD) in six independent cohorts from the EU and USA carry auto-Abs neutralizing IFN-α and/or -ω. The prevalence of these antibodies is highest in patients with encephalitis (∼40%), and that in individuals with silent WNV infection is as low as that in the general population. The odds ratios for WNVD in individuals with these auto-Abs relative to those without them in the general population range from 19.0 (95% CI 15.0-24.0, P value <10-15) for auto-Abs neutralizing only 100 pg/ml IFN-α and/or IFN-ω to 127.4 (CI 87.1-186.4, P value <10-15) for auto-Abs neutralizing both IFN-α and IFN-ω at a concentration of 10 ng/ml. These antibodies block the protective effect of IFN-α in Vero cells infected with WNV in vitro. Auto-Abs neutralizing IFN-α and/or IFN-ω underlie ∼40% of cases of WNV encephalitis

Pregnancies in women receiving renal transplant for lupus nephritis: Description of nine pregnancies and review of the literature

Background Few data are available on pregnancy in renal transplanted women for lupus nephritis (LN). Methods Among 38 women with LN who received a renal transplant in our Unit, three had nine pregnancies. During the pregnancies, patients were followed by a multidisciplinary team including gynecologists and nephrologists. Results Two patients received a living related and one a deceased kidney transplant. The immunosuppressive therapy consisted of steroids calcinurin inhibithors and mycophenolate mofetil. The last drug was substituted with azathioprine in prevision of pregnancy. All patients had normal renal function and urinalysis. In two patients some signs of immunological activity persisted after transplantation. Five pregnancies ended in miscarriage and four in live births. Two pregnancies were uneventful. Pre-eclampsia occurred in a hypertensive patient in two pregnancies that ended in preterm delivery in one case and in a small for gestation age in both cases. And finally, follow-up graft function and urinalysis continued to be normal in all patients. Conclusions After renal transplantation our LN women continue to have frequent miscarriages. The other pregnancies ended in live births and, with the exception of pre-eclampsia in a hypertensive patient, no renal or extra-renal complications occurred during or after pregnancy, even in cases with active immunological tests

Conservative surgical treatment of rectovaginal septum endometriosis

Between 1982 and 1991, we performed conservative operations on 11 women aged 23 to 39 years (mean 28 years) with extensive rectovaginal septum endometriosis. Before the intervention, severe deep dyspareunia was reported by 6 patients and moderate by 4, severe dysmenorrhea by 4 and moderate by 5, and severe acyclic pelvic pain by 2, moderate by 4, and mild by 1. The subjects underwent vaginoabdominal surgery with subtotal removal of the posterior vaginal fornix and excision of intraperitoneal endometriosis, with presacral neurectomy in 7 cases and low anterior rectal resection in 5. After a mean follow-up of 41 months, 6 women have no dyspareunia and 5 have mild discomfort, 4 have no dysmenorrhea, 3 have moderate and 4 mild menstrual pain, and 6 have mild acyclic disturbances. Three of nine infertile patients conceived. In selected young women wanting children, with pelvic pain symptoms unrelieved by medical treatment, a conservative vaginoabdominal surgical approach is feasible, and satisfactory therapeutic results can be obtained

Hysteroscopic metroplasty with resectoscope or microscissors for the correction of septate uterus

During 1990, we performed hysteroscopic incision of uterine septum in 23 women with repeated abortion. The patients were allocated randomly to metroplasty with resectoscope (12 patients in group 1) or microscissors (11 patients in group 2) to compare surgical feasibility and anatomic results with these instruments. The uterine cavity was distended by instillation of sorbitol and mannitol solution under manometric control. Two patients in group 1 and three in group 2 had a complete septum. In group 1, the mean operating time, plus or minus standard deviation (S.D.), was 22 +/- 6 minutes compared with 17 +/- 5 minutes in group 2 (p = 0.06). The mean amount of distension medium used, plus or minus S.D., was 890 +/- 153 milliliters in group 1 versus 671 +/- 170 milliliters in group 2 (p = 0.003). One woman in group 1 with complete uterine septum had a uterine perforation that was managed conservatively. Postoperative morbidity for the entire series was negligible. At follow-up ultrasonography and hysteroscopy performed two months postoperatively, a residual fundal notch > or = 1 centimeter deep was detected and corrected in four patients in group 1 and two in group 2. Our findings indicate that, in terms of operating time and efficacy, the resectoscope and microscissors are equally valid instruments to correct a septate uterus, with a feasibility rate of 100 percent

Does contraception modify the risk of endometriosis?

Long episodes of regular, prolonged, abundant menstrual flows are generally agreed to increase the risk of endometriosis. Since oral oestrogen-progestogen combinations reduce and intra-uterine contraceptive devices increase menstrual flow, an effect on the risk of development of endometriosis in women utilizing these forms of contraception could be expected. Analysis of the most recent epidemiological observations shows no consensus on a possible relationship between use of cyclic oral contraceptives and endometriosis, with an increase, a decrease, and no effect on the risk of developing the disease all being reported. A lower relative risk of endometriosis in previous users of the intrauterine contraceptive device was only found in two series, most of the other data suggesting a rise in risk or no effect. Further studies on the relationship between type of contraception and endometriosis are needed to demonstrate whether the risk of development of the disease could be influenced, and whether well tolerated, relatively inexpensive, long-term treatment might be available for symptomatic patients not desiring offspring