Management of pregnancy in autoimmune rheumatic diseases: maternal disease course, gestational and neonatal outcomes and use of medications in the prospectiveItalian P-RHEUM.it study.

OBJECTIVES: To investigate pregnancy outcomes in women with autoimmune rheumatic diseases (ARD) in the Italian prospective cohort study P-RHEUM.it. METHODS: Pregnant women with different ARD were enrolled for up to 20 gestational weeks in 29 Rheumatology Centres for 5 years (2018-2023). Maternal and infant information were collected in a web-based database. RESULTS: We analysed 866 pregnancies in 851 patients (systemic lupus erythematosus was the most represented disease, 19.6%). Maternal disease flares were observed in 135 (15.6%) pregnancies. 53 (6.1%) pregnancies were induced by assisted reproduction techniques, 61 (7%) ended in miscarriage and 11 (1.3%) underwent elective termination. Obstetrical complications occurred in 261 (30.1%) pregnancies, including 2.3% pre-eclampsia. Two cases of congenital heart block were observed out of 157 pregnancies (1.3%) with anti-Ro/SSA. Regarding treatments, 244 (28.2%) pregnancies were treated with glucocorticoids, 388 (44.8%) with hydroxychloroquine, 85 (9.8%) with conventional synthetic disease-modifying anti-rheumatic drugs and 122 (14.1%) with biological disease-modifying anti-rheumatic drugs. Live births were 794 (91.7%), mostly at term (84.9%); four perinatal deaths (0.5%) occurred. Among 790 newborns, 31 (3.9%) were small-for-gestational-age and 169 (21.4%) had perinatal complications. Exclusive maternal breast feeding was received by 404 (46.7%) neonates. The Edinburgh Postnatal Depression Scale was compiled by 414 women (52.4%); 89 (21.5%) scored positive for emotional distress. CONCLUSIONS: Multiple factors including preconception counselling and treat-to-target with pregnancy-compatible medications may have contributed to mitigate disease-related risk factors, yielding limited disease flares, good pregnancy outcomes and frequency of complications which were similar to the Italian general obstetric population. Disease-specific issues need to be further addressed to plan preventative measures.

Risk factors for damage accrual in primary antiphospholipid syndrome: A retrospective single-center cohort study.

BACKGROUND: Despite anticoagulant therapy, a antiphospholipid syndrome (APS) has a higher rate of recurrent events, which can lead to damage accrual and a negative impact on life quality. OBJECTIVES: To evaluate the risk factors and APS subsets associated with damage accrual. PATIENTS/METHODS: We conducted a retrospective single-center study. We reviewed the medical records of 282 APS patients, with a median age of 36 (IQR 30-46) years and a median of 195 (IQR 137-272) months. The primary endpoint was damage accrual during follow-up, defined as organ/tissue impairment present for at least six months or causing permanent loss. The secondary endpoints were early organ damage within six months of disease onset and death. RESULTS: Eighty (28.4%) patients presented damage accrual; 52.5% developed damage within six months of APS onset, and 41.3% had more than one organ involved. Neuropsychiatric involvement, affecting 38.8% of the patients, was the most frequent, followed by peripheral vasculopathy and renal involvement, 35% either. Death happened in 7 (2.5 %) patients; damage accrual was associated with a 6-fold risk of death [OR 6.7 (95% CI 1.3-35.1), p = 0.03]. Microangiopathy and non-criteria manifestations were independent risk factors for damage accrual with 5-fold and 4-fold higher risk, respectively [(OR 4.9 (95% CI 2.1-11.7), p < 0.0001 and (OR 3.8 (95% CI 1.5-10.1), p = 0.007]. The cumulative incidence of damage accrual increased by 5.7-fold and 3.6-fold in patients with microangiopathy and non-criteria manifestations. CONCLUSIONS: APS patients had a higher frequency of damage accrual. Microangiopathy and non-criteria manifestations were independent risk factors for damage accrual.

First Report of Anthracnose Caused by Colletotrichum nymphaeae on Strawberry Fruits in Central Argentina.

Strawberry (Fragaria x ananassa) production in Argentina extends to around 1700 hectares. Coronda city, located in Santa Fe province, is an important strawberry producer due to ideal agroecological conditions for culture and a high specialization for production. In November 2021, anthracnose symptoms were observed on strawberries cvs. 'San Andreas' and 'Splendor' in Coronda (31°58'S, 60°55'W), central Argentina. During these years, the incidence of the disease reached 40% of the production. Symptoms included 2-3 mm circular to irregular dark brown spots which enlarged rapidly and became sunken. Under high humidity conditions, concentric rings of pinhead-size salmon-colored acervuli developed on the lesions. The causal agent was isolated by touching acervuli with a sterile needle and monosporic cultures were obtained on PDA after 10 days at 25°C, with a 12-h light period. Colonies were white to gray on the top and orange on the underside, where concentric rings of salmon acervuli were clearly distinguished. The width and length of one hundred conidia were examined in three isolates (CF1, CF2, and CF3), ranging from 3.27 to 5.53 µm (avg.= 4.3 µm), and from 10.37 to 19.52 µm (avg.= 14.27 µm), respectively. The conidia were hyaline, smooth-walled, aseptate, and cylindric-clavate with one end round and one end acute. These morphological characteristics correspond to species belonging to the C. acutatum complex (Damm et al. 2012; Liu et al. 2022). To accurately identify the species, DNA was extracted from isolates, and ß-tubulin (TUB2), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and histone (HIS3) genes were partially amplified and sequenced (Vieira et al. 2020). TUB2, GAPDH, and HIS3 sequences presented a 100% of identity with species of Colletotrichum nymphaeae. The nucleotide sequences were deposited in GenBank (OR271556-OR271558, TUB2; OR271559-OR271561, GAPDH; and OR271562-OR271564, HIS3). Multilocus phylogenetic analyses performed with reference sequences (Damm et al. 2012) showed that the three isolates clustered with C. nymphaeae, in accordance with BLAST results. To confirm pathogenicity, each isolate was inoculated in eight detached fruits of the cultivar from which it was originally obtained. Two drops of 10 µl of conidial suspension (1x105 conidia per ml) were deposited in non-wounded areas on fruits previously disinfested with 1% sodium hypochlorite solution for 1 min and rinsed twice with sterile distilled water. Drops of sterile water were deposited in eight fruits as control. Pathogenicity tests were repeated twice. Fruits were kept in moist chamber (80+5% relative humidity) at 25°C for ten days. First symptoms appeared 4 days after inoculation. After that, all of the isolates produced symptoms identical to those previously described, whereas the controls remain symptomless. The pathogen was re-isolated from lesions, and identified as C. nymphaeae by morphological characteristics and based on the TUB2 sequences, as previously described. Strawberry anthracnose in Argentina was previously associated with Colletotrichum acutatum, C. gloeosporioides and C. fragariae species based on morphological characteristics (Ramallo et al. 2000; Monaco et al. 2000) but molecular identification was not performed until today. To our knowledge, this is the first report of C. nymphaeae causing anthracnose on strawberry in Argentina. This accurate identification will help to develop more efficient management strategies.

Antiphospholipid antibody carriers and patients with quiescent antiphospholipid syndrome show persistent subclinical complement activation.

OBJECTIVES: Complement activation has been advocated as one mechanism by which antiphospholipid antibodies (aPLs) can induce thrombosis. In patients with catastrophic aPL syndrome or re-thrombosis, enhanced complement activation was shown, even in quiescent phase of the disease. We aimed to assess complement activation and to investigate its association to clinical variables in aPL positive patients with a favorable disease course. METHODS: Subjects with at least two consecutive positive aPL antibody results obtained ≥12 weeks apart were enrolled. They were subjects without history of thrombosis or pregnancy morbidity (aPL carriers), patients with pregnancy morbidity alone (OAPS), and/or with arterial, venous, or small-vessel thrombosis (TAPS); all patients should have been free of symptoms for ≥2 years. Patients affected with systemic autoimmune diseases were excluded. Healthy age and sex-matched subjects were included as controls. Plasma C5a and C5b-9 levels were assessed by commercially available ELISA assays. Non-parametric Mann-Whitney test and Spearman's correlation were applied. RESULTS: Thirty-seven OAPS, 38 TAPS, 42 aPL carriers, and 30 healthy subjects were enrolled. Median C5a and C5b-9 levels were significantly higher in quiescent aPL positive patients (OAPS, TAPS, aPL carriers) compared with controls: C5a ng/ml 10.61 (IQR 6.87-15.46) vs 4.06 (2.66-7.35), p< 0.001; C5b-9 ng/ml 283.95 (175.8-439.40) vs 165.90 (124.23-236.8), p< 0.001. Similar C5a and C5b-9 levels were observed in OAPS and TAPS patients and aPL carriers. A positive correlation between C5b-9 median levels and the number of aPL positive tests was found (p= 0.002). CONCLUSIONS: The persistence of aPL antibodies is associated to a persistent subclinical activation of the complement cascade.

Prevalence and adverse consequences of delayed diagnosis and misdiagnosis in thrombotic antiphospholipid syndrome. An observational cohort study and a review of the literature.

OBIECTIVES: This study aims to prospectively evaluate the frequency and adverse consequences of diagnostic delay and misdiagnosis in a cohort of patients with thrombotic antiphospholipid syndrome (TAPS). In addition, a systematic review of the literature concerning the diagnostic delay and misdiagnosis of TAPS was carried out. METHODS: Patient enrollment occurred between 1999 and 2022. The study group was formed by TAPS patients whose diagnosis was delayed and those who were misdiagnosed. The control group was made up of patients who were timely and correctly diagnosed with TAPS. RESULTS: The literature review showed 42 misdiagnosed patients, 27 of them were in one retrospective cohort study and 15 in 13 case reports. One hundred sixty-one out of 189 patients (85.2%) received a timely, correct diagnosis of TAPS; 28 (14.8%) did not. The number of patients with diagnostic issues was significantly higher for the first period (1999-2010), and the number of patients with a correct diagnosis was significantly higher for the second one (2011-2022). When the clinical and laboratory characteristics of the patients with delayed diagnosis were compared with those with misdiagnosis, there was a significantly higher number of severe adverse consequences characterized by permanent disability or death in the latter group. The two most common types of misdiagnoses were systemic lupus erythematosus (6 cases, 46.1%) and cardiovascular diseases (4 cases, 30.8%). CONCLUSIONS: The study demonstrates that although knowledge about TAPS has improved over time, diagnostic delays and errors remains to be addressed as they are strongly associated to adverse consequences. Key Points •Although knowledge of thrombotic antiphospholipid syndrome has improved over time, it is still limited. •Diagnostic delay and misdiagnosis are still an important issue that remains to be addressed as they are strongly associated to adverse consequences. •The three more frequent misdiagnoses are multiple sclerosis, systemic lupus erythematosus and cardiovascular diseases.

Short and long-term outcomes of children with autoimmune congenital heart block treated with a combined maternal-neonatal therapy. A comparison study.

OBJECTIVE: The short and long-term outcomes of children with anti-Ro/La-related congenital heart block treated with a combined maternal-neonatal therapy protocol were compared with those of controls treated with other therapies. STUDY DESIGN: Sixteen mothers were treated during pregnancy with a therapy consisting of daily oral fluorinated steroids, weekly plasma exchange and fortnightly intravenous immunoglobulins and their neonates with intravenous immunoglobulins (study group); 19 mothers were treated with fluorinated steroids alone or associated to intravenous immunoglobulins or plasma exchange (control group). RESULT: The combined-therapy children showed a significantly lower progression rate from 2nd to 3rd degree block at birth, a significant increase in heart rate at birth and a significantly lower number of pacemaker implants during post-natal follow-up with respect to those treated with the other therapies. CONCLUSION: The combined therapy produced better short and long term outcomes with respect to the other therapies studied.

High plasma C5a and C5b-9 levels during quiescent phases are associated to severe antiphospholipid syndrome subsets.

OBJECTIVES: High plasma C5a and C5b-9 levels are considered a clear sign of complement activation. We aimed to evaluate the clinical significance of these two complement activation products during quiescent phases of thrombotic antiphospholipid syndrome (APS) by comparing their plasma levels in the different clinical subsets and relating them to the clinical characteristics and antiphospholipid antibody profile of the patients. METHODS: The three patient subsets studied were: i) thrombotic patients responsive to anti-vitamin K therapy (TAPS); ii) patients with refractory to vitamin K antagonists recurrent thrombosis (RAPS); iii) patients diagnosed with catastrophic APS (CAPS). Plasma C5a and C5b-9 levels were assessed using commercial ELISA assays. RESULYTS: Sixty-two quiescent APS patients were recruited: 40 were affected by TAPS, 13 by RAPS and 9 by CAPS. Data analysis showed that the TAPS patients had significantly lower levels of both complement activation products with respect to the RAPS and CAPS patients. In addition, C5a and/or C5b-9 significantly prevailed in the patients with small-vessel thrombosis, just as C5b-9 did in the triple antiphospholipid antibody positive patients. The ROC curve showed that the best cut-offs for C5a and C5b-9 levels had a higher sensitivity, specificity and likelihood ratio in the CAPS and RAPS groups than they did in the TAPS subset. CONCLUSIONS: These results suggest that the persistence of high plasma C5b-9 and C5a levels during quiescent phases identifies APS patients with more severe disease who may develop rethrombosis and benefit from complement inhibition treatment during an acute disease phase.

Long-term Outcome of Children Born to Women with Autoimmune Rheumatic Diseases: A Multicentre, Nationwide Study on 299 Randomly Selected Individuals.

The concern about the offspring's health is one of the reasons for a reduced family size of women with rheumatic diseases (RD). Increased risk of autoimmune diseases (AD) and neurodevelopmental disorders (ND) has been reported in children born to patients with RD. Within a nationwide survey about reproductive issues of women with RD, we aimed at exploring the long-term outcome of their children. By surveying 398 patients who received their diagnosis of RD during childbearing age (before the age of 45), information about the offspring were obtained from 230 women who declared to have had children. A total of 148 (64.3%) patients were affected by connective tissue diseases (CTD) and 82 (35.7%) by chronic arthritis. Data on 299 children (156 males, 52.1%; mean age at the time of interview 17.1 ± 9.7 years) were collected. Twelve children (4.0%), who were born to patients with CTD in 75% of the cases, were affected by AD (8 cases of celiac disease). Eleven children had a certified diagnosis of ND (3.6%; 6 cases of learning disabilities); 9 of them were born to mothers with CTD (5 after maternal diagnosis). No association was found between ND and prenatal exposure to either maternal autoantibodies or anti-rheumatic drugs. Absolute numbers of offspring affected by AD and ND were low in a multicentre cohort of Italian women with RD. This information can be helpful for the counselling about reproductive issues, as the health outcomes of the offspring might not be an issue which discourage women with RD from having children.

Transfusion-Transmitted Malaria of Plasmodium malariae in Palermo, Sicily.

Transfusion-transmitted malaria (TTM) is a rare occurrence with serious consequences for the recipient. In non-endemic areas, the incidence of transmission of malaria by transfusion is very low. We report a clinical case of transfusion-transmitted malaria due to Plasmodium malariae, which happened in a patient with acute hemorrhagic gastropathy.Case presentation: In April 2019, a 70-year-old Italian man with recurrent spiking fever for four days was diagnosed with a P. malariae infection, as confirmed using microscopy and real-time PCR. The patient had never been abroad, but about two months before, he had received a red blood cell transfusion for anemia. Regarding the donor, we revealed that they were a missionary priest who often went to tropical regions. Plasmodium spp. PCR was also used on donor blood to confirm the causal link. Discussion and Conclusions: The donations of asymptomatic blood donors who are predominantly "semi-immune" with very low parasitic loads are an issue. The main problem is related to transfusion-transmitted malaria. Our case suggests that P. malariae infections in semi-immune asymptomatic donors are a threat to transfusion safety. Currently, microscopy is considered the gold standard for the diagnosis of malaria but has limited sensitivity to detect low levels of parasitemia. Screening using serological tests and molecular tests, combined with the donor's questionnaire, should be used to reduce the cases of TTM.

An Update on Phytochemicals and Pharmacological Activities of the Genus Persicaria and Polygonum.

The discovery of new pharmaceutical identities, particularly anti-infective agents, represents an urgent need due to the increase in immunocompromised patients and the ineffectiveness/toxicity of the drugs currently used. The scientific community has recognized in the last decades the importance of the plant kingdom as a huge source of novel molecules which could act against different type of infections or illness. However, the great diversity of plant species makes it difficult to select them with probabilities of success, adding to the fact that existing information is difficult to find, it is atomized or disordered. Persicaria and Polygonum constitute two of the main representatives of the Polygonaceae family, which have been extensively used in traditional medicine worldwide. Important and structurally diverse bioactive compounds have been isolated from these genera of wild plants; among them, sesquiterpenes and flavonoids should be remarked. In this article, we firstly mention all the species reported with pharmacological use and their geographical distribution. Moreover, a number of tables which summarize an update detailing the type of natural product (extract or isolated compound), applied doses, displayed bioassays and the results obtained for the main bioactivities of these genera cited in the literature during the past 40 years. Antimicrobial, antioxidant, analgesic and anti-inflammatory, antinociceptive, anticancer, antiviral, antiparasitic, anti-diabetic, antipyretic, hepatoprotective, diuretic, gastroprotective and neuropharmacological activities were explored and reviewed in this work, concluding that both genera could be the source for upcoming molecules to treat different human diseases.

Low Preconception Complement Levels Are Associated with Adverse Pregnancy Outcomes in a Multicenter Study of 260 Pregnancies in 197 Women with Antiphospholipid Syndrome or Carriers of Antiphospholipid Antibodies.

Antiphospholipid antibodies (aPL) can induce fetal loss in experimental animal models. Human studies did find hypocomplementemia associated with pregnancy complications in patients with antiphospholipid syndrome (APS), but these results are not unanimously confirmed. To investigate if the detection of low C3/C4 could be considered a risk factor for adverse pregnancy outcomes (APO) in APS and aPL carriers' pregnancies we performed a multicenter study including 503 pregnancies from 11 Italian and 1 Russian centers. Data in women with APS and asymptomatic carriers with persistently positive aPL and preconception complement levels were available for 260 pregnancies. In pregnancies with low preconception C3/C4, a significantly higher prevalence of pregnancy losses was observed (p = 0.008). A subgroup analysis focusing on triple aPL-positive patients found that preconception low C3 and/or C4 levels were associated with an increased rate of pregnancy loss (p = 0.05). Our findings confirm that decreased complement levels before pregnancy are associated with increased risk of APO. This has been seen only in women with triple aPL positivity, indeed single or double positivity does not show this trend. Complement levels are cheap and easy to be measured therefore they could represent a useful aid to identify patients at increased risk of pregnancy loss.

Predictive factors for switching in patients with psoriatic arthritis undergoing anti-TNFα, anti-IL12/23, or anti-IL17 drugs: a 15-year monocentric real-life study.

OBJECTIVES: We aimed to evaluate the (a) potential predictors of first biological disease-modifying anti-rheumatic drug (bDMARD) failure and (b) factors associated with failure of multiple therapies in psoriatic arthritis (PsA). MATERIALS AND METHODS: We enrolled consecutive PsA patients attending our unit and undergoing bDMARDs during 2004-2020. Disease characteristics, previous/ongoing treatments, comorbidities, and follow-up duration were recorded. Disease activity and functional and clinimetric scores were recorded at baseline and yearly and were compared between switchers and non-switchers, and within switchers according to the reasons for switching. Effectiveness was evaluated over time with descriptive statistics; multivariate Cox and logistic regression models were used to evaluate predictors of response and failure of multiple bDMARDs. Kaplan-Meier curves were used to assess differences in time-to-first bDMARD discontinuation. Infections and adverse events were recorded. RESULTS: Two hundred sixty-four patients were included (117 (44.32%) females, mean age 56 years, mean PsA duration 15 years); 117 (44.32%) switched bDMARDs at least once. Switchers were mostly females, with higher Psoriasis Area and Severity Index and worse Health Assessment Questionnaire at baseline. Mean time-to-first bDMARD discontinuation was 72 months; 2-year and 5-year retention rates were 75% and 60%, respectively. Survival curves for anti-TNFα/anti-IL12/23/anti-IL17 were similar (p = 0.66). Main reasons for switching were inefficacy (67.52%) and adverse events (25.7%). Female sex was associated with a higher risk of first bDMARD discontinuation (HR = 2.39; 95% CI: 1.50-3.81) and failure of multiple bDMARDs (OR = 1.99; 95% CI: 1.07-3.69); initiating therapy before 2015 was protective (HR = 0.40; 95% CI: 0.22-0.73). CONCLUSIONS: Survival rate was good for anti-TNFα and other bDMARDs. Female sex was a predictor of first bDMARD discontinuation, unlike mechanism of action, comorbidities, and BMI. Key Points • Drug survival in PsA patients was confirmed be greater for the first bDMARD administered. • In case of failure of the first bDMARD, switching/swapping proved a good treatment option, as reflected by a persistent satisfactory effectiveness with second-line bDMARDs and so subsequent switches. • Female sex may constitute a predisposing risk factor for flare and therapeutic switches. • Discontinuation or switching of biologics due to mechanism of action, comorbidities tolerability and BMI did not seem to impact first bDMARD withdrawal.

The first thrombotic event in purely obstetric antiphospholipid syndrome patients and in antiphospholipid antibody carriers: comparison of incidence and characteristics.

PURPOSE: The long-term risk of thrombosis after pregnancy in women with purely obstetric antiphospholipid syndrome (OAPS) is not well defined. The current study's primary outcome was to evaluate the incidence and characteristics of the first thrombotic event in OAPS, identifying the risk factors for thrombosis in OAPS was its secondary one. METHODS: Patients with purely OAPS were consecutively enrolled between September 1999 and September 2019. Subjects without a history of pregnancy morbidity or thrombosis but with persistent positivity for one or more antiphospholipid antibodies (aPL carriers) made up the control group. The study groups included 94 OAPS patients and 124 aPL carriers who were matched for clinical and laboratory parameters. RESULTS: An event rate of 0.49/100 patient years was registered in OAPS patients during a mean follow-up of 8.7 years ± 5.5 SD. Kaplan-Meier survival analysis revealed that the cumulative incidence of thromboembolic events was not significantly different in OAPS patients vs aPL carriers. Arterial thrombosis and cerebrovascular events were the more frequent types of vascular involvement in the two groups. As far as risk factors for thrombosis were concerned, the presence of lupus anticoagulant significantly prevailed in both thrombotic OAPS patients and thrombotic aPL carriers with respect to purely OAPS patients and aPL carriers who did not develop thrombosis (p = 0.01 and p = 0.00, respectively). CONCLUSION: Just as for aPL carriers, closer monitoring and possibly, a pharmacological prophylaxis should be reserved for OAPS patients at highest risk of developing the first thrombotic event.

The efficacy and safety of second-line treatments of refractory and/or high risk pregnant antiphospholipid syndrome patients. A systematic literature review analyzing 313 pregnancies.

OBJECTIVE: The most efficacious strategy to manage pregnant patients with antiphospholipid syndrome (APS) refractory to conventional heparin/low-dose aspirin treatment or at high risk of adverse pregnancy outcomes has not been determined with any degree of certainty. The study set out to evaluate the efficacy and safety of the second-line treatments most frequently used in addition to conventional therapy, and the data were analyzed to identify which is/are associated to the best pregnancy outcomes. METHODS: A systematic review of the literature on studies concerning second-line treatments for refractory and/or high risk pregnant APS women published between February 2006 and February 2020 was conducted. The records were retrieved by searching Medline via Pubmed, the Web of Science platform, the Cochrane library database and clinicaltrials.gov. RESULTS: Fourteen studies met the eligibility criteria of the review: six retrospective cohort studies, one case-control, one case-series and six case reports. The results of single treatment protocols based upon hydroxychloroquine (HCQ), low-dose steroids (LDS), intravenous immunoglobulins (IVIG), plasma exchange (PE) or pravastatin and of combination protocols based upon HCQ+LDS, IVIG+LDS, PE+LDS and PE+IVIG used during 313 pregnancies in 303 APS women were analyzed and compared. The second-line treatments produced 261/313 (83.4%) live births; severe pregnancy complications were registered in 75/313 (24%) pregnancies. Drug side-effects were observed in 3/313 (0.9%) pregnancies. Statistical analysis identified a significantly higher live birth rate and/or a significantly lower number of severe complications in the pregnancies treated with IVIG, HCQ, pravastatin, PE+IVIG and PE+LDS. CONCLUSION: Our results suggest using low-dose IVIG (< 2 g/Kg/month) or HCQ 400 mg/day starting before pregnancy in women with APS refractory to conventional therapy, while high-dose IVIG (2 g/Kg/month) associated with PE or alone in those with high risk±refractory APS.

Skin ulcers in systemic sclerosis: correlation with clinical phenotype in a monocentric cohort from the north-east of Italy.

OBJECTIVES: To evaluate the prevalence of skin ulcers (SUs) and their association with clinical phenotype in a monocentric cohort of patients affected with systemic sclerosis (SSc). METHODS: Patients affected with SSc (ACR/EULAR 2013 criteria) in regular follow-up at the Rheumatology Unit of Padova University Hospital, Italy, were considered and retrospectively evaluated. Demographic, clinical and laboratory data, organ involvement and therapy were recorded. We analysed the occurrence, timing (single episode, recurrent/chronic) and site of SUs. The association between SUs and demographic and clinical variables was assessed by logistic regression analysis. RESULTS: We evaluated 211 SSc patients, aged 60.8±12.4 years, 187 (89%) females, 147 (70%) affected with limited cutaneous SSc. During a median follow-up of 120 months (50-216), 105 (50%) patients experienced at least one episode of SU; among them, 66% had recurrent or persistent SUs. Patients with a history of SUs compared with those never affected were younger at SSc diagnosis (p=0.009), had more frequently a diffuse cutaneous form (p=0.001), chronic anaemia (p<0.001), systemic inflammation (p=0.001), lung (p=0.002) and cardiac (p=0.004) involvement, and calcinosis (p=0.001). At multivariate analysis a younger age at SSc diagnosis (p=0.031), articular involvement (p=0.005) and telangiectasia (p=0.003) were independently associated with SUs. Telangiectasia, articular involvement, chronic anaemia and inflammatory state were found to be associated with the recurrence/chronicisation of SUs. CONCLUSIONS: SUs represent a common complication in our cohort of patients with a long-term follow-up. The association of SUs with some clinical manifestations of SSc suggests a combined role of microcirculatory damage and inflammation in their origin.

Different Responses in Mandarin Cultivars Uncover a Role of Cuticular Waxes in the Resistance to Citrus Canker.

'Okitsu' is a mandarin cultivar showing substantial resistance to X. citri subsp. citri (X. citri). We have previously shown that this cultivar has significantly lower canker incidence and severity than 'Clemenules', particularly during early stages of leaf development in the field. This differential response is only seen when the leaves are inoculated by spraying, suggesting that leaf surface contributes to resistance. In this work, we have studied structural and chemical properties of leaf surface barriers of both cultivars. Ultrastructural analysis showed a thicker cuticle covering epidermal surface and guard cells in young 'Okitsu' leaves than in 'Clemenules'. This thicker cuticle was associated with a smaller stomatal aperture and reduced cuticle permeability. These findings correlated with an accumulation of cuticular wax components, including primary alcohols, alkanes, and fatty acids. None of these differences were observed in mature leaves, where both cultivars are equally resistant to the bacterium. Remarkably, mechanical alteration of cuticular thickness of young 'Okitsu' leaves allows canker development. Furthermore, cuticular waxes extracted from young 'Okitsu' leaves have higher antibacterial activity against X. citri than 'Clemenules'. Taken together, these data suggest that a faster development of epicuticular waxes in 'Okitsu' leaves play a central role in its resistance to X. citri.

Deterioro cognitivo sin demencia en la insuficiencia renal crónica terminal. datos de un centro argentino / Cognitive impairment without dementia in end-stage chronic renal disease. data from an argentinian center

RESUMEN Objetivos: Evaluar el desempeño cognitivo en una población hemodialítica. Conocer la relación entre la insuficiencias renal crónica terminal (IRCT) y la presencia de deterioro cognitivo, así como la influencia del tratamiento hemodialítico. Identificar otras variables que podrían influir en el desempeño cognitivo.Material y métodos:Estudio cuasiexperimental, de corte transversal. Se incluyeron 25 sujetos adultos, con IRCT en hemodiálisis. Grupo control compuesto por 4 sujetos sanos. Se registraron los antecedentes clínicos, información sobre diálisis y análisis de laboratorio. Se realizaron entrevistas individuales aplicando test Neuropsipor único operador. Resultados:El 36% de los pacientes presentaba alteraciones en atención y funciones ejecutivas, yel 24% presentaba alteración en memoria. Los pacientes con resultados alterados en atención y funciones ejecutivas eran de mayor edad y en mayor proporción mujeres, aunque sin significación estadística, además había porcentaje superior de HTA, cardiopatía isquémica y tabaquismo. Este grupo tenía niveles más bajos de hematocrito (32.11 ± 4.96 vs 35.69 ± 1.40, p=0.01) y hemoglobina (10.67 ± 1.55 vs 11.98 ± 0.51, P=<0.01), y tendencia a valores de colesterol total y triglicéridos más bajos. Los pacientes con resultados alterados en memoria presentaban mayor cantidad de episodios de hipotensión (5.83 ± 2.64 vs 2.63 ± 3.29; p=0.04), mayor proporción de pacientes con HTA (66.7% vs 26.3%; p=0.07) y niveles más bajos de hemoglobina (10.72 ± 1.75 vs 11.76 ± 0.84, P=0.05), sin presentar diferencias significativas respecto a niveles de metabolismo fosfocálcico, PTHi, albúmina, glucemia ni lípidos.Conclusiones: Los pacientes en hemodiálisis (HD) son una población de alto riesgo y con mayor prevalencia de trastornos cognitivos. Tanto las causas comórbidas, asociadas con enfermedad vascular crónica, como los trastornos de inflamación y malnutrición, son factores que se encuentran asociados a peores resultados.

ABSTRACT Objectives: To assess cognitive performance in a hemodialysis population. To know relationship between IRCT and the presence of cognitive impairment, as well as the influence of hemodialysis treatment. Identify other variables that could influence cognitive performance.Methods: quasi-experimental study design, cross section. 25 adult subjects with ESRD on hemodialysis were included. Control group consisted of 4 healthy subjects. Medicalhistories, information on dialysis and laboratory tests were recorded. Individual interviews were conducted using the Neuropsi test being performed by a single operator.Results: 36% of patients had alterations in attention and executive functions and 24% had impaired memory. Patients with abnormal results in attention and executive functions had older and proportion of women although not statistically significant, plus higher percentage of hypertension, ischemic heart disease and smoking. This group had lower levels of hematocrit (32.11 ± 4.96 vs 35.69 ± 1.40, p = 0.01) and hemoglobin (10.67 ± 1.55 vs 11.98 ± 0.51, P = <0.01) and a tendency to total cholesterol and lower triglycerides. Patients with abnormal results in memory had a greater number of episodes of hypotension (5.83 ± 2.64 vs 2.63 ± 3.29; p = 0.04), a higher proportion of patients with hypertension (66.7% vs 26.3%; p = 0.07) and more levels low hemoglobin (10.72 ± 1.75 vs 11.76 ± 0.84, P = 0.05); without significant differences in levels of calcium and phosphorus metabolism, PTH, albumin, glucose or lipids.Conclusions: HD patients are a high-risk population and higher prevalence of cognitive disorders. Both comorbid causes associated with chronic vascular disease and inflammation disorders and malnutrition are factors that are associated with worse outcomes.

Upgrading Therapy Strategy Improves Pregnancy Outcome in Antiphospholipid Syndrome: A Cohort Management Study.

The current study evaluates the efficacy and safety of different treatment strategies for pregnant patients with antiphospholipid syndrome. One hundred twenty-seven consecutive pregnancies were assessed; 87 (68.5%) with a history of pregnancy morbidity alone were treated with prophylactic low molecular weight heparin (LMWH) + low-dose aspirin (LDA, 100 mg) (group I) and 40 (31.5%) with a history of thrombosis and/or severe pregnancy complications with therapeutic LMWH + LDA (group II). LMWH doses were increased throughout the pregnancies depending on the patients' weight gain, and treatment was switched to a more intensive one at the first sign of maternal/fetal complications. The study's primary outcome was live births. There were no significant differences in live birth rate between group I (95.4%) and group II (87.5%). Even fetal complication rate was similar in the two groups; group II nevertheless had a higher prevalence of maternal and neonatal complications (p = 0.0005 and p = 0.01, respectively) and registered a significantly lower gestational age at delivery and birth weight (p = 0.0001 and p = 0.0005, respectively). Two patients in group I switched to group II therapy, six patients in group II switched to a more intensive treatment strategy (weekly plasma exchange + fortnightly intravenous immunoglobulins in addition to therapeutic LMWH + LDA). The multivariate analysis uncovered that triple antiphospholipid antibodies positivity was an independent factor leading to a more intensive therapy. All eight switched patients achieved a live birth. Study results revealed that adjusted LMWH doses and switching therapy at first signs of severe pregnancy complications led to a high rate of live births in antiphospholipid syndrome patients.

An observational multicentre study on the efficacy and safety of assisted reproductive technologies in women with rheumatic diseases.

OBJECTIVES: The aim was to determine whether assisted reproductive technologies (ARTs) confer additional risk in rheumatic patients (in terms of disease flare and fetal-maternal complications) and whether, if performed, their efficacy is affected by maternal disease. METHODS: Sixty infertile rheumatic women undergoing 111 ART cycles were included. Clinical pregnancy rate, live birth rate, maternal disease flares and maternal-fetal complications were recorded. RESULTS: One hundred and eleven ART cycles in 60 women were analysed. We reported 46 pregnancies (41.4%), 3 (3.1%) cases of ovarian hyperstimulation syndrome and no cases of thrombosis during stimulation, pregnancy and puerperium. One or more maternal complication was reported in 13 (30.2%) pregnancies, and fetal complications occurred in 11 fetuses (21.1%). The live birth rate was 98%, but we reported three (6%) perinatal deaths in the first days of life. During puerperium, we recorded one (2.5%) post-partum haemorrhage and one (2.5%) articular flare. CONCLUSION: The safety and efficacy of the ARTs, demonstrated in the general population, seems to be confirmed also in rheumatic patients. No evidence was found to advise against their application, and the choice of therapy should be made depending on the patient's risk profile, irrespective of whether the pregnancy is natural or artificial induced.