Victims of drug facilitated sexual assault aged 13-24: a cross sectional study on the pool of users of a sexual violence relief centre in Northern Italy.

This cross-sectional study aimed to assess the association between drugs and alcohol intake and sexual abuse in adolescents, otherwise defined as Drug Facilitated Sexual Assault (DFSA). We considered the survivors who accessed care at the Centre "Soccorso Violenza Sessuale" (SVS - Sexual Violence Relief Centre) in Turin (Italy), between May 2003 and May 2022. We found that 973 patients aged 13-24 among which 228 were victims of DFSA. Epidemiological and anamnestic aspects of the episode of sexual violence were examined, with a specific focus on investigating the alcohol and/or drug intake as reported by the victim, along with the results of the toxicological analysis. the study further accounts for the variations caused by the COVID-19 pandemic on DFSA-related accesses. Our findings show that 23% of adolescents accessing care at SVS were subjected to DFSA. Six out ten adolescents knew their aggressor, at times a partner (10%) oran acquaintance (43%). In 12% of cases violence was perpetrated by a group of people (12%). Almost 90% of young victims described alcohol consumption, while 37% reported drug use at the time of the assault. Alcohol taken alone or in combination with other substances was the most detected drug in our sample throughout the period considered. Given the large use of psychoactive substances among adolescents, it is imperative to implement harm reduction strategies alongside educational activities aimed at fostering awareness about consent. Health personnel should be trained to manage the needs of victims of DFSA clinically and forensically.

2023 ACR/EULAR classification criteria in existing research cohorts: an international study.

OBJECTIVE: Assessing the impact of the updated ACR/EULAR APS classification criteria to our research cohort. METHODS: Consecutive patients who tested persistently positive for at least one aPL in the last three years were enrolled. The first APS Sydney index event was considered and computed for the comparison between Sydney and 2023 APS criteria. When computing the 2023 APS criteria, additional manifestations were also considered. RESULTS: The cohort comprised 249 patients (185 with APS and 64 aPL carriers according to Sydney criteria). The 185 patients had as first index event VT in 55 cases (29.8%) AT in 63 (34%) and PM in 67 (36.2%). When applying the updated criteria, 90 subjects (48.7%) failed to reach the composite score of the new criteria. The percentage of thrombotic APS per Sydney criteria decreased from 47.3% to 34.9% because of high cardiovascular risk in 23 cases, IgM aPL profile in 6 cases and in 2 patients for both reasons. Patients with PM decreased from 26.9-3.2% (39 cases of recurrent early pregnancy loss and 20 of fetal losses). Consequently, the percentage of aPL carriers increased from 26% to 61%. When looking at the disease evolution at follow-up, 32 additional patients out of 90 (35.6%) fulfilled the new APS criteria, after developing additional clinical manifestation following index event. CONCLUSION: When applying the new APS criteria to our research cohort, not negligible differences exist in patients' classification. A multidisciplinary approach will be mandatory to assess the impact into research and, ultimately, patient's care of new criteria.

Impact of Ebola and COVID-19 on maternal, neonatal, and child health care among populations affected by conflicts: a scoping review exploring demand and supply-side barriers and solutions.

INTRODUCTION: Armed conflicts have a severe impact on the health of women and children. Global health emergencies such as pandemics and disease outbreaks further exacerbate the challenges faced by vulnerable populations in accessing maternal, neonatal, and child healthcare (MNCH). There is a lack of evidence that summarizes the challenges faced by conflict-affected pregnant women, mothers, and children in accessing MNCH services during global health emergencies, mainly the Ebola and COVID-19 pandemics. This scoping review aimed to analyze studies evaluating and addressing barriers to accessing comprehensive MNCH services during Ebola and COVID-19 emergencies in populations affected by conflict. METHODS: The search was conducted on PubMed, Scopus, and Web of Science databases using terms related to Ebola and COVID-19, conflicts, and MNCH. Original studies published between 1990 and 2022 were retrieved. Articles addressing the challenges in accessing MNCH-related services during pandemics in conflict-affected settings were included. Thematic analysis was performed to categorize the findings and identify barriers and solutions. RESULTS: Twenty-nine studies met the inclusion criteria. Challenges were identified in various MNCH domains, including antenatal care, intrapartum care, postnatal care, vaccination, family planning, and the management of childhood illnesses. Ebola-related supply-side challenges mainly concerned accessibility issues, health workforce constraints, and the adoption of stringent protocols. COVID-19 has resulted in barriers related to access to care, challenges pertaining to the health workforce, and new service adoption. On the demand-side, Ebola- and COVID-19-related risks and apprehensions were the leading barriers in accessing MNCH care. Community constraints on utilizing services during Ebola were caused by a lack of trust and awareness. Demand-side challenges of COVID-19 included fear of disease, language barriers, and communication difficulties. Strategies such as partnerships, strengthening of health systems, service innovation, and community-based initiatives have been employed to overcome these barriers. CONCLUSION: Global health emergencies amplify the barriers to accessing MNCH services faced by conflict-affected populations. Cultural, linguistic, and supply-side factors are key challenges affecting various MNCH domains. Community-sensitive initiatives enhancing primary health care (PHC), mobile clinics, or outreach programs, and the integration of MNCH into PHC delivery should be implemented. Efforts should prioritize the well-being and empowerment of vulnerable populations. Addressing these barriers is crucial for achieving universal health coverage and the Sustainable Development Goals.

Negative consequences of conflict-related sexual violence on survivors: a systematic review of qualitative evidence.

BACKGROUND: Conflicts exacerbate dynamics of power and inequalities through violence normalization, which acts as a facilitator for conflict-related sexual violence. Literature addressing its negative outcomes on survivors is scant. The aim of this systematic review was to analyze the qualitative evidence reported in scientific literature and focusing on the negative consequences of conflict-related sexual violence on victims' physical, psychological, and social dimensions of health in a gender-inclusive and disaggregated form. METHODS: A literature search was conducted on January 13, 2023 on Pubmed, Scopus, and PsychArticles. The search strings combined two blocks of terms related to sexual violence and conflict. A time filter was applied, limiting the search to studies published in the last ten years. Information regarding the main characteristics and design of the study, survivors and their experience, and about conflict-related sexual violence was collected. The negative consequences of conflict-related sexual violence on the physical, psychological, and social dimension of victims were extracted according to the Biopsychosocial model of health. The review followed the Joanna Briggs Institute methodology for systematic reviews and relied on the Preferred Reporting Items for Systematic reviews and Meta-Analyses. RESULTS: After full text review, 23 articles met the inclusion criteria, with 18 of them reporting negative repercussions on physical health, all of them highlighting adverse psychological outcomes, and 21 disclosing unfavorable social consequences. The negative outcomes described in multiple studies were sexual and reproductive health issues, the most mentioned being pregnancy, manifestations of symptoms attributable to post-traumatic stress disorder, and stigma. A number of barriers to access to care were presented as emerging findings. CONCLUSIONS: This review provided an analysis of the negative consequences of conflict-related sexual violence on survivors, thus highlighting the importance of qualitative evidence in understanding these outcomes and addressing barriers to access to care. Conflict-related sexual violence is a sexual and reproductive health issue. Sexuality education is needed at individual, community, and provider level, challenging gender norms and roles and encompassing gender-based violence. Gender-inclusive protocols and services need to be implemented to address the specific needs of all victims. Governments should advocate for SRHRs and translate health policies into services targeting survivors of CRSV.

Daratumumab monotherapy for refractory lupus nephritis.

Treatment-refractory lupus nephritis (LN) has a high risk of a poor outcome and is often life-threatening. Here we report a case series of six patients (one male and five females) with a median age of 41.3 years (range, 20-61 years) with refractory LN who received renal biopsies and were subsequently treated with intravenous daratumumab, an anti-CD38 monoclonal antibody (weekly for 8 weeks, followed by eight biweekly infusions and up to eight monthly infusions). One patient did not show any improvement after 6 months of therapy, and daratumumab was discontinued. In five patients, the mean disease activity, as assessed by the Systemic Lupus Erythematosus Disease Activity 2000 index, decreased from 10.8 before treatment to 3.6 at 12 months after treatment. Mean proteinuria (5.6 g per 24 h to 0.8 g per 24 h) and mean serum creatinine (2.3 mg dl-1 to 1.5 mg dl-1) also decreased after 12 months. Improvement of clinical symptoms was accompanied by seroconversion of anti-double-stranded DNA antibodies; decreases in median interferon-gamma levels, B cell maturation antigen and soluble CD163 levels; and increases in C4 and interleukin-10 levels. These data suggest that daratumumab monotherapy warrants further exploration as a potential treatment for refractory LN.

Vulnerability of migrant women during disasters: a scoping review of the literature.

BACKGROUND: Disasters have an unequal impact on the population because of differences in conditions of vulnerability, exposure, and capacity. Migrants and women are among the groups that are at greater risk for and disproportionately affected by disasters. However, despite the large body of evidence that analyzes their vulnerability separately, disaster research that targets migrant women is scant. The aim of this scoping review was to analyze the published scientific literature concerning the vulnerability of migrant women and the consequent negative impact they experience during disasters. METHODS: A literature search was conducted on December 15th, 2021 on Pubmed, Scopus, and Web of Science databases. No time filter was applied to the search. Information regarding the article's main characteristics and design, migrant women and their migration experience, as well as about the type of disaster was collected. The factors responsible for the vulnerability of migrant women and the negative outcomes experienced during a disaster were extracted and inductively clustered in main themes reflecting several vulnerability pathways. The review followed the Joanna Briggs Institute methodology for scoping reviews and relied on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). RESULTS: After full text review, 14 articles met the inclusion criteria. All of them adopted a qualitative methodology and focused on COVID-19. The pandemic negatively affected migrant women, by triggering numerous drivers that increased their level of exposure and vulnerability. Overall, six vulnerability factors have been identified: legal status, poverty conditions, pre-existing health conditions, limited agency, gender inequality and language and cultural barriers. These resulted in nine impacts: worsening of mental health status, poor access to care, worsening of physical health conditions, fraud, exacerbation of poverty, gender-based violence, jeopardization of educational path, and unfulfillment of their religious needs. CONCLUSIONS: This review provided an analysis of the vulnerability factors of migrant women and the pathways leading to negative outcomes during a disaster. Overall, the COVID-19 pandemic demonstrated that health equity is a goal that is still far to reach. The post-pandemic era should constitute the momentum for thoroughly addressing the social determinants of health that systematically marginalize the most vulnerable groups.

New Frontiers in Autoimmune Diagnostics: A Systematic Review on Saliva Testing.

(1) Background: Immunological laboratory testing is known to be complex, and it is usually performed in tertiary referral centers. Many criticalities affect diagnostic immunological testing, such as limited availability, the need for specifically trained laboratory staff, and potential difficulties in collecting blood samples, especially in the most vulnerable patients, i.e., the elderly and children. For this reason, the identification of a new feasible and reliable methodology for autoantibody detection is urgently needed. (2) Methods: We designed a systematic review to investigate the available literature on the utilization of saliva samples for immunological testing. (3) Results: A total of 170 articles were identified. Eighteen studies met the inclusion criteria, accounting for 1059 patients and 671 controls. The saliva collection method was mostly represented by passive drooling (11/18, 61%), and the most frequently described methodology for antibody detection was ELISA (12/18, 67%). The analysis included 392 patients with rheumatoid arthritis, 161 with systemic lupus erythematosus, 131 with type 1 diabetes mellitus, 116 with primary biliary cholangitis, 100 with pemphigus vulgaris, 50 with bullous pemphigoids, 49 with Sjogren syndrome, 39 with celiac disease, 10 with primary antiphospholipid syndromes, 8 with undifferentiated connective tissue disease, 2 with systemic sclerosis, and 1 with autoimmune thyroiditis. The majority of the reviewed studies involved adequate controls, and saliva testing allowed for a clear distinction of patients (10/12 studies, 83%). More than half of the papers showed a correlation between saliva and serum results (10/18, 55%) for autoantibody detection, with varying rates of correlation, sensitivity, and specificity. Interestingly, many papers showed a correlation between saliva antibody results and clinical manifestations. (4) Conclusions: Saliva testing might represent an appealing alternative to serum-based testing for autoantibody detection, considering the correspondence with serum testing results and the correlation with clinical manifestations. Nonetheless, standardization of sample collection processing, maintenance, and detection methodology has yet to be fully addressed.

"How we treat" clinical dilemmas in antiphospholipid syndrome: A case-based approach.

Antiphospholipid syndrome (APS) is an autoimmune condition characterized by thrombosis (arterial, venous, and microvascular) and/or pregnancy morbidity occurring in subjects persistently positive for antiphospholipid antibodies (aPL). While the APS classification criteria are being currently updated to improve homogeneity in clinical research, patients who seek medical treatment often have a variety of laboratory and clinical characteristics that may not completely fulfill the classification criteria for overt APS. Those cases might represent a challenge in terms of treatment and overall management. We aim to present a collection of challenging scenarios of patients who tested positive for aPL and to discuss available literature to guide the therapeutic strategies.

Open-label, prospective, phase II descriptive pilot trial of belimumab therapy for refractory and/or non-criteria manifestations of antiphospholipid syndrome: study protocol.

OBJECTIVES: To evaluate the safety and tolerability of belimumab given for 24 months in patients persistently positive for antiphospholipid antibodies (aPL) with clinical features attributable to aPL [refractory and/or non-criteria manifestations of the antiphospholipid syndrome (APS)]. METHODS: In this investigator-initiated, single-centre, open-label, prospective, phase II descriptive pilot trial, belimumab will be administered in 15 patients attending San Giovanni Bosco Hospital (Turin) showing refractory and/or non-criteria manifestations of APS. Subjects will receive belimumab 10 mg/kg intravenously (in addition to their ongoing APS treatment) with regimen at 0, 2, 4 weeks and every 4 weeks thereafter (up to week 104). Study endpoints determined at 4, 16, 24, 36, 52 and 104 weeks will include: primary (safety and adverse events) and secondary outcomes, such as changes in clinical outcomes (recurrent thromboses, thrombocytopenia, haemolytic anaemia, cardiovascular events, skin ulcer, aPL-related nephropathy and cognitive dysfunction), laboratory outcomes (routine tests, aPL, ENA and anti-dsDNA tests, thrombin generation assay, interferon-signature analysis, lymphocytes immunophenotyping, BLyS determination) and QoL evaluation. RESULTS: Study endpoints determined at 4, 16, 24, 36, 52 and 104 weeks will include: primary (safety and adverse events) and secondary outcomes, such as changes in clinical outcomes (recurrent thromboses, thrombocytopenia, haemolytic anaemia, cardiovascular events, skin ulcer, aPL-related nephropathy and cognitive dysfunction), laboratory outcomes (routine tests, aPL, ENA and anti-dsDNA tests, thrombin generation assay, interferon-signature analysis, lymphocytes immunophenotyping, BLyS determination) and QoL evaluation. CONCLUSIONS: Targeting B-cells is emerging as an appealing strategy for patients with APS. Preliminary observations showed aPL negativisation after starting therapy with belimumab. The clinical relevance of these findings will be investigated in this prospective study. If confirmed, the current 'anti-thrombotic' approach to APS patients could be complemented, at least in selected cases, with an 'immunomodulatory' strategy.

Thrombin generation assay and lupus anticoagulant synergically distinguish populations of patients with antiphospholipid antibodies.

AIM: To apply thrombin generation assay (TGA) in a large cohort of antiphospholipid antibodies (aPL)-positive patients. MATERIAL AND METHODS: 108 patients were tested with TGA and lupus anticoagulant (LA) testing and divided according to their aPL profile. Briefly, 21 patients were positive for anti-phosphatidylserine (aPS)/prothrombin (PT) IgG/IgM (group1), 29 for anti-ß2-glycoprotein-I (aß2GPI) and anti-cardiolipin (aCL) IgG/IgM (group2), 31 for aPS/PT, aß2GPI and aCL IgG/IgM (group3), 27 for aPS/PT and/or aß2GPI+aCL IgM at low-titres (group4). 31 healthy donors (HDs) and 24 controls treated with vitamin K antagonists (VKA) were included. RESULTS: The most deranged TGA and LA profiles were observed in tetra-positive patients (group3) that differed significantly to the other groups, thus those with isolated, double or triple aPL-positivity. Moreover, when comparing the TGA profile of all antiphospholipid syndrome (APS) patients, aPL-carriers, HDs and VKA controls, we observed that the aPL+ patients (especially APS) showed a distinctive profile that allowed to distinguish them from the other groups with significantly higher tLag and tPeak, and lower Peak and area under the curve.When focusing on APS clinical manifestations, patients with a high-risk profile (group3) showed significant differences from those presenting low-titres aPL (group 4) regarding the number of venous events (p=0.04), recurrence of any thrombotic event (p=0.01), of arterial events (5 vs 0, p=0.02), the occurrence of TIA (p=0.04), DVT (p=0.02) and, when analysing extracriteria manifestations, of peripheral artery disease (p=0.04). CONCLUSIONS: TGA seems a valuable approach to stratify aPL+ patients according to their risk profile. The differences among different populations of autoantibodies specificities could be considered a translational validation of the increased thrombotic risk of patients with triple or tetra aPL-positivity.

Serum Biomarkers of Renal Fibrosis: A Systematic Review.

Chronic kidney disease (CKD) is a widely diffuse pathological condition which deeply impacts upon an affected patient's quality of life and its worldwide rate is predicted to further rise. The main biological mechanism underlying CKD is renal fibrosis, a non-reversible process representing, for the affected system, a point of no return of tissue damage and dysfunction, deeply reducing the possible therapeutic strategies at the disposal of physicians. The best tool clinicians can use to address the extent of renal fibrosis at any level (glomeruli, tubule-interstitium, vasculature) is kidney biopsy that, despite its overall safety, remains an invasive procedure showing some shortcomings. Thus, the identification of novel non-invasive renal fibrosis biomarkers would be of fundamental importance. Here, when systematically reviewing the available evidence on serological biomarkers associated with renal fibrosis evaluated in patients suffering from CKD in the last five years, we found that despite the presence of several promising biomarkers, the level of observed evidence is still very scattered. Probably, the use of multiple measures capable of addressing different aspects involved in this condition would be the most suitable way to capture the high complexity characterizing the renal fibrotic process, having consequently a great impact on clinical practice by maximizing prevention, diagnosis, and management.

Assessing the cardiovascular risk in patients with systemic lupus erythematosus: QRISK and GAPSS scores head-to-head.

OBJECTIVES: We aimed to apply and compare the QRISK3 and the adjusted Global AntiPhospholipid Syndrome (APS) Score (aGAPSS) in a cohort of systemic lupus erythematosus (SLE) patients, with and without a concomitant diagnosis of APS, in order to assess their augmented risk of developing cardiovascular diseases (CVDs). METHODS: Patients (25-85 yo) with a diagnosis of SLE and/or of Secondary APS (SAPS) were included. QRISK3 was calculated using the official online calculator; aGAPSS using the validated point-values based on aPL-profile and independent risk factors. RESULTS: The cohort included 142 SLE patients: 34 SAPS (23.9%) and 108 SLE patients without APS (76.1%).When considering all the cohort, patients with cerebrovascular/coronary events showed higher values of aGAPSS (10.1 ± 6.2 vs. 5.8 ± 6.1; p = 0.007), but not of the QRISK3. Furthermore, a significant association was observed between the occurrence of these events and high-risk aGAPSS: p = 0.03 for aGAPSS≥8, p = 0.01 for aGAPSS ≥9, p = 0.008 for aGAPSS ≥10. aGAPSS strongly correlated with the occurrence of any thrombotic event, both at the uni- and multivariate analysis (p = 0.012 and p = 0.009). Male gender also resulted to positively correlate with the occurrence of any thrombotic event at both uni- and multivariate analysis (p = 0.017 and p = 0.03). Focusing on aPL-profile, regardless the diagnosis, we found a statistical significance only for aGAPSS (aPL+ =9.6 ± 6.3 vs. aPL- = 4.1 ± 5.1; p < 0.001). CONCLUSIONS: Despite QRISK3 being more accurate than traditional risk score in predicting CVD risk in SLE patients, aGAPSS appears to be the most valuable tool for this purpose.

Clinical Delphi on aPL Negativization: Report from the APS Study Group of the Italian Society for Rheumatology (SIR-APS).

BACKGROUND: The rate of antiphospholipid antibody (aPL) negativization in antiphospholipid syndrome (APS) patients is uncertain, but it is estimated to be as high as 8%. Currently, a consensus definition of aPL negativization is lacking, as well as international recommendations on how to approach treatment in patients with a persistent aPL-negative seroconversion. AIM: The aim of the Delphi survey was to evaluate the clinical approach and level of consensus among experts from the APS Study Group of the Italian Society for Rheumatology (SIR-APS) in different clinical scenarios. METHODS: Experts of SIR-APS were contacted using a survey methodology. RESULTS: A structured survey was circulated among 30 experts. Up to 90% of the interviewed experts agreed on defining aPL negativization as the presence of two negative determinations, 1 year apart (90%). Almost full consensus exists among experts in some clinical settings, including: (1) the role of aPL negativization in the management of a thrombotic event determined by concomitant presence of cardiovascular risk factors, both modifiable and not modifiable (90%); (2) approach to young patients with triple aPL positivity who experienced pulmonary arterial thrombotic events and tested negative for aPL detection after 5 years of vitamin K antagonist (VKA) treatment (90%); (3) the use of "extra criteria" aPL antibody testing before pondering VKA suspension (93%). CONCLUSION: A substantial agreement exists among experts on how to define aPL negativization. VKA suspension should be embraced with extreme caution, particularly in case of previous thrombotic events and/or triple aPL positivity. Nevertheless, VKA cessation might be considered when risk factors are carefully monitored/treated and the presence of "extra criteria" aPL is ruled out.

Disease evolution in a long-term follow-up of 104 undifferentiated connective tissue disease patients.

OBJECTIVES: To investigate the rate of disease evolution in a cohort of patients with undifferentiated connective tissue disease (UCTD) and to determine clinical and immunological features more frequently associated with disease progression. METHODS: This retrospective single-centre long-term follow-up cohort study included patients with UCTD diagnosis, ANA positive, with a follow-up of at least 2 years. RESULTS: A total of 100 UCTD patients were recruited. During the follow-up (6.2±2.1 years), 44 patients (44%) developed novel clinical and/or laboratory features (rate of development patient/year of 7%), and 21 patients (21%) evolved into a definite connective tissue disease (CTD) after a mean time of 7±5.5 years with a rate of disease evolution (patient/year) of 3%. New clinical manifestations (39 patients) included: joints (36%), haematological (30%), cutaneous (13%), pulmonary (10%) and renal (10%) involvement. New laboratory findings (17 patients (17%)) included: 2 anti-ENA positivity, 3 anti-dsDNA antibodies positivity and 6 low complement levels. At follow-up, 13 patients (61.9%) met the classification criteria for systemic lupus erythematosus, 1 patient (4.8%) for mixed CTD, 5 patients (23.8%) for systemic sclerosis and 2 patients (9.5%) for Sjögren's syndrome. Patients evolving towards a new diagnosis had longer disease duration (15.2±9.7 years vs. 10±5.8 years; respectively, p<0.005), had a higher prevalence of anti-Ro/SSA antibodies (63.2% vs. 28.4%; respectively, p<0.05) and anti-RNP antibodies (21.1% vs. 7.4%; respectively, p<0.05). The statistical difference was also confirmed after the multivariate analysis. CONCLUSIONS: Up to 45% of UCTD patients might develop novel clinical and/or laboratory features during the follow-up, leading to evolution into a definite CTD in 1 out 5 cases.

Cerebrovascular events in patients with isolated anti-phosphatidyl-serine/prothrombin antibodies.

The interest of extra-criteria antiphospholipid antibodies is growing, especially in patients negative for conventional antibodies. In this study we aimed to assess the clinical utility of anti-phosphatidyl-serine/prothrombin antibodies (aPS/PT) testing in patients negative for Beta2-Glycoprotein 1(ß2GPI)-dependent tests, for identifying antiphospholipid syndrome (APS) patients that developed cerebrovascular events (CVE). When screening APS patients attending our center, out of 119 aPS/PT IgG/IgM-positive patients, thus patients negative for aß2GPI and aCL, 42 patients (35%) tested negative for ß2GPI-dependent tests and were tested with thrombin generation assay (TGA). Ten patients (24%), with isolated aPS/PT IgG/IgM, had a history of CVE. Lupus anticoagulant (LA)-positive test was more frequently observed in patients with CVE (8/22 vs. 2/20; p = 0.045). Out of the 10 patients who experienced CVE, 3 patients were aPS/PT IgG positive (all LA positive), and 8 patients were aPS/PT IgM positive (6/8 LA positive). One patient was positive for both aPS/PT IgG and IgM. LA-positive patients had only high titers of aPS/PT IgG/IgM, all of them being ≥ 80 U/ml, while the 2 LA-negative patients were aPS/PT IgM positive with medium titers [40-60 U/ml]. LA-positive patients had significantly altered TGA profile when compared to those who were LA negative, considering all TGA parameters. LA-positive patients had significantly higher tLag (8.4 ± 3.3 min vs. 6.6 ± 1.8 min; p = 0.046), higher tPeak (14 ± 4.3 min vs. 11 ± 2.7 min; p = 0.015) and lower Peak (207 ± 152 nM vs. 356.3 ± 104.7 nM; p < 0.001) and lower AUC (2109.7 ± 1006.9 nM vs. 2772.5 ± 776.8 nM; p = 0.033). The use of aPS/PT might be of help in identifying patients with CVE and APS, as also confirmed by TGA testing.

Reducing the diagnostic delay in Antiphospholipid Syndrome over time: a real world observation.

BACKGROUND: Antiphospholipid Syndrome (APS) is a rare autoimmune disorder with an estimated prevalence of 40-50 cases per 100.000 persons. Patients suffering from low prevalence diseases are more likely to face diagnostic challenges, given the limited knowledge of most clinicians. The main aim of this study was to investigate the time between symptoms occurrence and the diagnosis of APS patients using the Piedmont and Aosta Valley Rare Disease Registry. Secondly, to evaluate the individual impact of the diagnostic gap by gathering patients' personal experiences through a self-administered questionnaire. RESULTS: Data from the Piedmont and Aosta Valley Rare Disease Registry was used. In addition, personal experiences were analyzed through a self-administered questionnaire. A total of 740 APS patients included in the Piedmont and Aosta Valley Rare Disease Registry were analyzed. Diagnostic delay (as defined by time between symptoms' occurrence and the diagnosis of APS) was significantly reduced over time. In particular, when comparing the diagnostic delay between patients diagnosed between 1983 and 1999 and patients diagnosed between 2000 and 2015, we found a significant statistical difference (Mann-Whithey U Test; mean rank 1216.6 vs. 1066.9, respectively; p < 0.0001). When analyzing the self-administered questionnaires, patients with a perception of having suffered for a diagnostic delay had a higher prevalence of symptoms suggestive of an autoimmune condition but not highly suggestive of APS (45%), followed by "extra criteria" APS manifestation (30%) and by thrombotic events (25%). The first clinical manifestation of patients who did not have the perception of having suffered a diagnostic delay was thrombotic events (45.5%), followed by autoimmune manifestation not linked to APS (45.5%), and "extra criteria" APS manifestations (9%). CONCLUSIONS: While the diagnostic delay of APS has been reduced during the last years, the time between symptoms occurrence and the diagnosis of rare diseases still represents a critical issue to be addressed in order to prevent major complications.