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PurposeTo report on our 43-year single-center experience with children operated on for Choledochal Malformations (CMs), focusing on long-term results and Quality of life (QoL).Materials and methodsAll consecutive pediatric patients with CMs who underwent surgical treatment at our center between October 1980 and December 2022 were enrolled in this retrospective study. We focused on long-term postoperative complications (POCs), considered to be complications arising at least 5 years after surgery. We analyzed QoL status once patients reached adulthood, comparing the results with a control group of the same age and sex.ResultsOne hundred and thirteen patients underwent open excision of CMs with a Roux-en-Y hepaticojejunostomy (HJ). The median follow-up was 8.95 years (IQR: 3.74–24.41). Major long-term POCs occurred in six patients (8.9%), with a median presentation of 11 years after surgery. The oldest patient is currently 51. No cases of biliary malignancy were detected. The QoL of our patients was comparable with the control group.ConclusionOur experience suggests that open complete excision of CMs with HJ achieves excellent results in terms of long-term postoperative outcomes. However, since the most severe complications can occur many years after surgery, international cooperation is advisable to define a precise transitional care follow-up protocol.

Background: To date, no good marker for screening or disease monitoring of endometrial cancer (EC) is available. The aims of this study were to investigate HE4 gene, protein expression and serum HE4 (sHE4) levels in a panel of ECs and normal endometria (NEs) and to correlate sHE4 with patient clinicopathological characteristics and prognosis. Methods: Using quantitative real-time PCR we tested 46 ECs and 20 NEs for HE4 gene expression. Protein expression was analysed by immunohistochemistry on tissue microarrays in 153 ECs and 33 NEs. Pre-operative serum samples from 138 EC and 76 NE patients were analysed with HE4–EIA assay. Association between sHE4 and patient clinicopathological characteristics or outcome was evaluated. Results: Protein and HE4 gene were significantly upregulated in EC tissues and sera, compared with controls. High sHE4 levels were significantly associated with worse EC clinical characteristics. By univariate survival analysis, high sHE4 levels significantly correlated with decreased overall survival, progression-free survival and disease-free survival, retaining their independent prognostic value on the poorly differentiated EC cohort. Conclusion: We demonstrate, for the first time, that high sHE4 levels correlates with an aggressive EC phenotype and may constitute an independent prognostic factor for poorly differentiated-ECs. Determination of sHE4 could be clinically useful in identifying high-risk EC patients for a more aggressive adjuvant therapy.

The search for biomarkers of response to antipsychotic medications is hindered by difficulties inherent in the topic or related to persistent methodological difficulties, such as high rates of anticipated discontinuation and consequent distortions in the imputation of missing data. Because early response to antipsychotics represents a sufficiently reliable index of the subsequent treatment response in patients with schizophrenia, we undertook a real-world, genome-wide association study (GWAS) with the aim of identifying genetic predictors of response to risperidone after 2 weeks in 86 patients with schizophrenia. Limited to the associations reaching significance in the GWAS, confirmatory analysis relative to risperidone response over 9 months was also designed involving 97 patients (European only) enroled in the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) genetic substudy. The GWAS revealed a significant association (false discovery rate 0.02) of the single-nucleotide polymorphism rs2133450 inside the GRM7 gene with Emsley’s positive domain derived from the positive and negative syndrome scale (PANSS). Patients with the rs2133450 CC genotype presented poorer improvement in the positive domain over 2 weeks, with odds ratios of 12.68 (95% CI, 3.51–45.76) and 6.95 (95% confidence interval (CI), 2.37–20.37) compared with patients with the AA and AC genotypes, respectively. Compared with A homozygotes, rs2133450 C homozygotes enroled in the CATIE-derived confirmatory analysis showed less improvement in Emsley’s positive, excited and depression domains, positive and general PANSS subtypes, and total PANSS after 9 months of treatment with risperidone. The original GWAS and the CATIE-derived confirmatory analysis support the proposal that the rs2133450 may have translational relevance as a predictor of response to risperidone.

Background: To our knowledge, no study assessed the association between dietary patterns and nasopharyngeal carcinoma (NPC) in low-incidence areas. Methods: We examined this association in a hospital-based case–control study carried out in Italy between 1992 and 2008, including 198 incident NPC cases and 594 controls. A posteriori dietary patterns were identified through principal component factor analysis performed on 28 nutrients and minerals derived from a 78-item food-frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional multiple logistic regression models on tertiles of factor scores. Results: We identified five dietary patterns named Animal products , Starch-rich , Vitamins and fibre , Animal unsaturated fatty acids (AUFAs) , and Vegetable unsaturated fatty acids (VUFAs) . The Animal product (OR=2.62, 95% CI=1.67–4.13, for the highest vs lowest score tertile), Starch-rich (OR=2.05, 95% CI=1.27–3.33), and VUFA (OR=1.90, 95% CI=1.22–2.96) patterns were positively associated with NPC. The AUFA pattern showed a positive association of borderline significance, whereas the Vitamins and fibre pattern was nonsignificantly but inversely associated with NPC. Conclusions: These findings suggest that diets rich in animal products, starch, and fats are positively related to NPC risk in this low-incidence country.

BackgroundSystemic Lupus Erythematosus (SLE) is characterised by a fluctuating course. To achieve sustained remission is the ultimate goal of maintenance treatment. However remission is difficult to define in SLE. In 2014, an international Task Force named DORIS proposed four definitions of remission.1 ObjectivesAim of this study was to evaluate the performance of the DORIS algorithm in comparison to the remission status as defined by clinical judgement and to identify the frequency of remission as determined by DORIS for each clinical disease pattern.MethodsMonocentric retrospective study. Among all SLE patients followed at the Lupus Clinic between 2014 and 2016, we enrolled patients fulfilling the SLICC 2012 criteria who were visited at least once in 2016 and who had at least 5 biannual medical examinations in the previous 2 years. Definitions of remission according to DORIS, Clinical Remission, and disease patterns are reported in table 1.Results101 SLE patients were enrolled for this study (94% female, mean age 45 years). 17.8% of patients were in remission in all the 5 time-points, vice versa 29.7% of patients never got into remission. 17.8% of patients have been in remission for 24 months, while 21.8% of patients less then 6 months. Mean duration of DORIS remission was 7.96 months. The most prevalent disease patter were RR (41,6%) and CQ (41,6%), while CA pattern was present in 16,8% of patients. DORIS remission was most frequently achieved in CQ pattern (65.2% of visits), less frequently in CA (5.9%). 294 visits out of 505 (58%) were defined as “non-remission” according to DORIS. cSLEDAI above zero was the item that most frequently accounted for “non-remission”, particularly urinary and haematological (as reported in figure 1). In 229 (43.3%) visits there was a disagreement between DORIS and clinical judgement: the reasons for discordant results were respectively: a) self-management of steroids dosage and precautionary increase of steroids in the suspect of a flare in 7.1%; b) cSLEDAI >0 in 27.2%, PGA≥0.5 in 12.6%, more than one of these items in 53.1%.Abstract SAT0433 – Table 1Definition of Remission according to Doris, Definition of Clinical Remission according to Clinical judgement; Definition of disease pattern. PGA: Physician Global Assessment; cSLEDAI: clinical SLEDAIAbstract SAT0433 – Figure 1Items are responsible of disagreement between DORIS and Clinical definition of RemissionConclusionsNearly 40% of the visits displayed a disagreement between clinical judgement of remission and DORIS remission. This may be attributable mainly to a different approach in evaluating patients: longitudinal by clinical judgement and cross-sectional by DORIS. As compared to clinical judgement of remission, the DORIS definition is not designed to capture “low disease activity”, particularly patients who carry a PGA between 0.5 and 1 and those who require a medium dosage of steroids in the frame of a CA pattern.Reference[1] van Vollenhoven R, et al. Ann Rheum Dis2017Mar;76(3):554–561.Disclosure of InterestNone declared

Congenital heart block (CHB) is due to placental transfer of maternal anti-Ro/SSA autoantibodies to the fetus. The prevalence of CHB has been estimated as 1-2% in anti-Ro/SSA women while the recurrence rate is 16-19% (1). This condition is associated with a high rate of fetal/neonatal mortality and most of the cases requires pacemaker (PM) pacing. Given the rarity of CHB, limited data are available regarding the long-term follow-up of the offspring other than the cardiovascular complications. The results of the Italian Registry of the autoimmune congenital heart block were recently described (2). A peculiarity of this cohort was that most of the mothers had an established diagnosis of systemic autoimmune disease at CHB detection, in contrast with other registries where CHB was mostly incidentally detected in healthy women. Here we report an update, with the preliminary data regarding the long-term outcome of patients with CHB, their unaffected siblings and health controls born from mothers positive for Ro/SSA. Data regarding demography, treatment, maternal, neonatal outcome, and follow-up were collected through an online electronic datasheet. A dedicated questionnaire was created with the aim to investigate general health, cardiovascular follow-up, and frequency of autoimmune diseases. One-hundred and five cases of CHB in 99 patients were included from 1969 to December 2020. CHB was mostly detected in utero (97 cases, 92.3%) with 8 neonatal cases. Third degree CHB occurred in 71 cases (67.6%). Child mortality was observed in 29 (27.6%) cases: 20 in utero, 7 during neonatal period and 2 during childhood. Overall, a PM was implanted in 54 out of the 85 live births (63.5%). Then, our cohort was divided into 2 subgroups: pregnancy that occurred before (N=61) and after 2010 (N=44) with the aim to evaluate possible differences among the subgroups. Whereas mortality, PM, CHB degree were similar, CHB more frequently occurred in the last 10 years among Ro/SSA asymptomatic carriers than in the group of pregnancies before 2010 (53.6% vs 32.8%, p=0.038). Questionnaires from 14 surviving CHB cases, 8 unaffected siblings 12 controls born from mothers Ro/SSA positive were collected. Among CHB cases, 6 were males and 8 females, median age 12 years (range 6-28). All presented a third degree CHB, 10 required a neonatal PM pacing and one had an implantable ECG recorder. PM was substituted at least once in 9 patients, the oldest patient had to change it four times. No dilated cardiomyopathy occurred and most of the patients maintain an annual follow-up. Two cases of autoimmune diseases were registered among CHB cases, one idiopathic juvenile arthritis and one Cogan's vasculitis, both born from mothers with Sjogren Syndrome. Four cases of neurodevelopmental disorders occurred: three cases of learning disabilities (one in each group) and one case of speech disorder in the sibling group. In addition, a CHB case presented a stress disorder linked to frequent hospitalizations. This registry is an ongoing project aiming at collecting all Italian CHB. Moreover, here we reported the preliminary data concerning the evaluation of long-term follow-up of CHB patients. Our data, even if need to be confirmed in larger cohort, seems reassuring: no differences were reported comparing CHB patients with unaffected siblings or controls. [1]Brito-Zéron et al. Nat Rev Rheumatol 2015;11:301-312. [2]Fredi M et al. Front Cardiovasc Med. 2019 Feb 28;6:11. None declared

BackgroundThe outcome of Systemic Lupus Erythematosus(SLE) pregnancies has dramatically improved thanks to pregnancy planning, multidisciplinary management and close monitoring during pregnancy. In our experience, programmed pregnancies in SLE patients had similar rates of pregnancy losses as compared to general obstetric population, but there are still open issues on some pregnancy complications that more frequently affect SLE patients.ObjectivesTo analyse the obstetric outcome of SLE patients, according to specific therapy received during pregnancy.MethodsA monocentric, retrospective study of 98 SLE patients with a total of 134 pregnancies followed prospectively by multidisciplinary team(1987–2015). Adverse Pregnancy Outcomes(APOs) were defined as one of the followings:premature miscarriage(<10 th week), intrauterine fetal death(>10 th week), perinatal death(<30 th day of life), severe preterm birth(<34 th week) and preterm birth(between 34th-36th weeks). We also evaluated the frequency of other pregnancy complications such as preterm premature rupture of membranes(pPROM) and pre-eclampsia(PE).ResultsAmong the 134 pregnancies(including 3 twin pregnancies), flares occurred in 10 (7.5%) and APOs in 39 (29.1%) cases (table 1). pPROM complicated 9 pregnancies, all resulted in preterm deliveries, including 3 severe preterm birth; PE complicated 6 pregnancies resulting in 2 preterm birth, 1 intrauterine fetal death, 1 perinatal death and 2 term birth. The rates of APOs, pPROM and PE were compared according to receiving or not a specific therapy: hydroxychloroquine(HCQ), low dose aspirin(LDA), immunosuppressant(IS) during the overall pregnancy and corticosteroids>35 mg/week(CS) during the 1 st, the 2nd and the 3rd trimester. No statistical significant association was found between a specific therapy and the rate of PE. HCQ and LDA did not significantly affected the rate of APOs or pPROM while pregnancies exposed to IS showed a higher frequency of APOs(47% vs 20%, p0.003), in particular premature miscarriages(16% vs 2%, p0.007). Pregnancies exposed to CS had higher frequency of APOs(1 st trimester 44% vs 28%, p0.015; 2nd trimester 36% vs 13% p0.004; 3rd trimester 34% vs 14%, p0.019). Considering only the 120 pregnancies resulted in live birth, those exposed to CS had higher frequency of preterm birth(1 st trimester p0.006; 2nd trimester p0.023; 3rd trimester p0.011) (table 2). In particular, pregnancies exposed to CS in the 1 st trimester had higher frequency of preterm birth on 34th-36th w(p0.017), while pregnancies exposed in the 3rd trimester had a higher frequency of preterm birth before 34th w(p0.038). Furthermore, a higher frequency of pPROM was observed in those exposed to CS(1 st trimester p0.001; 2nd trimester p0.003; 3rd trimester p0.001).Abstract FRI0361 – Table 1frequency of APOs, pPROM and PE in the 134 analysed pregnanciesAbstract FRI0361 – Table 2frequency of preterm birth and pPROM among the 120 live birth, according to exposure (or not) to corticosteroids >35 mg/week during the three trimesters* 1 st trimester; ** 2nd trimester; *** 3rd trimesterConclusionsUse of IS seems to be associated with premature miscarriages; this could reflect their use in patients with a more severe disease phenotype. The exposure to CS in doses greater than 35 mg/w in the 1 st trimester seems to be associated with preterm birth at 34th-36th w, while in the 3rd trimester with severe preterm birth(<34 th w), that could be related to the strong association observed between CS use and pPROM.Disclosure of InterestNone declared

BackgroundCardiac neonatal lupus is due to placental transfer of maternal anti-Ro/SSA and anti-La/SSB autoantibodies to the fetus and mainly includes congenital heart block (CHB) and dilated cardiomyopathy. The prevalence of CHB has been estimated as 1%–2% in anti-Ro/SSA women while the recurrence rate is 16%–19%(.1 This condition is associated with a high rate of fetal/neonatal mortality and in the majority of cases requires pacemaker pacing.2–6 ObjectivesThe rarity of this condition requires the establishment of collaborative registries in order to improve our knowledge. Here we report the data of the ongoing Italian Registry of the autoimmune congenital heart block (Lu.Ne), which was created in 2016MethodsThe aim was to collect retrospective and prospective pregnancies complicated with CHB in patients with antibodies. Data regarding demography, treatment, maternal and neonatal outcome and follow-up were collected through an online electronic datasheet prepared in a Research Electronic Data Capture platform.ResultsEighty-six cases of CHB were collected in 82 women with 85 pregnancies that occurred between 1969–2016. CHB was mostly detected in utero (81 cases, 90.6%) with 5 neonatal CHB. Demographic description of the mothers, pregnancy outcomes and treatment are reported in table 1. Child mortality was observed in 22 (25.5%) cases: 12 fetal, 5 termination of pregnancy and 5 postnatal. Maternal and fetal risk factors for fetal mortality were analysed and, at univariate analysis, factors associated with death were an earlier detection of CHB (20.9±0.9 weeks vs 24.8±5.4 weeks; p=0.007), hydrops (p=0.002;OR=11.3;CI95%1.84–69.2) and pericardial effusion (p=0.025;OR >100;CI95%2.88->100).ConclusionsThe Lu.Ne registry is an ongoing project aiming at collecting all Italian CHB. Our data showed similar rate of fetal/neonatal death and of PM implantation previously reported. We confirmed that hydrops and pericardial effusion are risk factors for fetal death. A peculiarity of our cohorts is that the majority of the mothers (59%) had an established diagnosis of systemic autoimmune disease at CHB detection. This is in contrast with other registries showing that usually CHB was incidentally detected in healthy women and related to the recruiting Centres all belonging to Rheumatology Society. The collection of cases from Gynaecological and Paediatric Centres, planned in the next months, will complete our analysisReferences[1] Brucato, et al. Arth Rheum2001;1831–35.[2] Eliasson H, et al. Circulation2011;124:1919–26.[3] Izmirly PM, et al. Circulation2011;124:1927–35.[4] Levesque K, et al. Autoimmun Rev2015;14:1154–60.[5] Lopes LM, et al. Circulation2008;118:1268–75.[6] Van den Berg NW, et al. Int J Cardiol2016;225:167–171.AcknowledgementsThis project was funded by Italian Society of RheumatologyDisclosure of InterestNone declared

Severe oral mucositis is a major cause of morbidity following allogeneic hematopoietic stem cell transplantation (AHSCT). Cryotherapy, that is, the application of ice chips on the mucosa of the oral cavity during the administration of antineoplastic agents, may reduce the incidence and severity of chemotherapy-related oral mucositis. In this multicenter randomized study, we addressed whether cryotherapy during MTX administration is effective in the prevention of severe oral mucositis in patients undergoing myeloablative AHSCT. One hundred and thirty patients undergoing myeloablative AHSCT and MTX-containing GVHD prophylaxis were enrolled and randomized to receive or not receive cryotherapy during MTX administration. The incidence of severe (grade 3-4) oral mucositis, the primary end point of the study, was comparable in patients receiving or not cryotherapy. Moreover, no difference was observed in the incidence of oral mucositis grade 2-4 and the duration of oral mucositis grade 3-4 or 2-4, or in the kinetics of mucositis over time. In univariate and multivariate analysis, severe oral mucositis correlated with TBI in the conditioning regimen and lack of folinic acid rescue following MTX administration. Thus, cryotherapy during MTX administration does not reduce severe oral mucositis in patients undergoing myeloablative allogeneic HSCT. Future studies will assess cryotherapy before allogeneic HSCT.

This study identifies the genetic fingerprint of poorly differentiated endometrioid endometrial carcinomas (G3-EEC) and analyses the potential utility of trefoil factor 3 (TFF3) as novel serum marker in G3-EEC. Affymetrix microarrays were used to identify the gene expression patterns of 19 snap-frozen G3-EEC and 15 normal endometrium (NE) biopsies. Quantitative real-time PCR (qRT-PCR) and immunohistochemistry were used to validate TFF3 expression. Finally, TFF3 serum levels were determined by ELISA in 25 G3-EEC patients, 42 healthy controls, and in 13 endometrial hyperplasia patients. Hierarchical cluster analysis showed TFF3 as the top differentially expressed gene between 363 upregulated genes in G3-EEC, when compared with NE. Trefoil factor 3 gene expression levels analysed by qRT-PCR significantly correlated with Affymetrix results ( P <0.001; rs=0.85). By immunohistochemistry, TFF3 protein was significatively more expressed in EEC compared with NE ( P <0.01), with cytoplasmatic positivity in 79% G3-EEC and 18% NE. Patients harbouring G3-EECs had significantly higher TFF3 serum concentration by ELISA when compared with healthy patients ( P <0.001) or patients harbouring endometrial hyperplasia ( P =0.012). In conclusion, TFF3 is highly expressed at gene and protein level in G3-EEC. Further investigations on a wider set of samples are warranted to validate TFF3 as a novel serum marker for early detection and/or monitoring of G3-EEC patients.