Overlap syndrome of autoimmune hepatitis and primary biliary cholangitis complicated with atypical hepatocellular carcinoma: a case report.

BACKGROUND: Hepatocellular carcinoma (HCC) is a primary tumor of the liver. The majority of HCCs are associated most frequently with chronic B or C viral hepatitis, alcohol intake or aflatoxin exposure. Cirrhosis is a strong risk factor associated with HCC. The causes of liver cirrhosis are chronic viral hepatitis, alcohol intake, metabolic diseases (NAFLD), hemocromathosis, alfa 1 antitrypsisn deficiency. All aetiologic forms of cirrhosis are at risk to be complicated by HCC development, but the risk is higher for patients diagnosed with chronic viral hepatitis. Comparing to the above-mentioned causes, PBC and AIH are less associated with the risk of HCC development. A 71-year old Caucasian female previously diagnosed with overlap syndrome (AIH type 1 and PBC-ANA, SMA and AMA antibodies positive), liver cirrhosis, a nodule in the VI/VIIth hepatic segment, systemic sclerosis sine scleroderma, Hashimoto's thyroiditis, antiphospholipid syndrome, gastric antral vascular ectasia (GAVE) (with 2 previous sessions of argon plasma coagulation), cholecystectomy, arterial hypertension and nephro-angiosclerosis presented to the 2nd Department of Internal Medicine in Cluj-Napoca for a follow-up. The patient was following treatment with UDCA (Ursodeoxycholic acid), azathioprine, Plaquenil, calcium channel blockers, angiotensin-converting-enzyme inhibitor, calcium and vitamin D supplementation. The abdominal ultrasound showed a subcapsular hypoechoic nodule with a diameter of 29 mm (at the moment of the diagnosis the diameter was 9/10 mm) in the VI/VIIth hepatic segment. The contrast-enhanced ultrasound (CEUS) characterised the nodule as specific for hepatocellular carcinoma (LI-RADS 5). On MRI with gadoxetate disodium the nodule was hypovascular, non-specific, being classified as LI-RADS 3. An atypical resection of the VIIth hepatic segment was performed and the histohistological examination and imunohistochemistry (Hep Par-a positive, Glypican3 positive, CD34 positive) revealed a moderately differentiated hepatocellular carcinoma (G2), pT2 N0 M0 L0 V1 R0. CONCLUSION: Autoimmune hepatitis, PBC and the overlap syndrome are less associated with the development of liver cirrhosis and HCC than other chronic liver diseases, especially if other risk factors are not associated. This case highlights the importance of a proper surveillance of cirrhotic patients every 6 months including abdominal ultrasound and AFP levels is crucial for an early diagnosis of a HCC.

Determinants of health-related quality of life across the spectrum of connective tissue diseases using latent profile analysis: results from the LEAP cohort.

OBJECTIVES: Poor health-related quality of life (HRQoL) is well recognized in patients with CTD. We hypothesized that subgroups of patients across the spectrum of CTD experience different HRQoL patterns and aimed to determine patient-level characteristics associated with these different subgroups. METHODS: Using the eight continuous domains of the Medical Outcomes Study 36-item Short Form (SF-36) questionnaire we performed data-driven clustering to derive latent profiles (LPs) of patients with distinct HRQoL patterns. Multivariable ordinal logistic regression was used to determine patient-level characteristics associated with each HRQoL subgroup identified. RESULTS: A total of 309 CTD patients completed the SF-36 questionnaire. The most impaired SF-36 domains in each disease group were vitality, general health and bodily pain. The physical component of the SF-36 was consistently more impaired compared with the mental component, with similar scores across disease groups. Three LPs were identified with poor [n = 89 (29%)], average [n = 190 (61.4%)] and excellent [n = 30 (9.7%)] HRQoL. LPs were not associated with diagnostic grouping or autoantibody profiles. Black background [odds ratio (OR) 0.22 (95% CI 0.08, 0.63)], Indo-Asian background [OR 0.39 (95% CI 0.19, 0.78)], concomitant fibromyalgia [OR 0.40 (95% CI 0.20, 0.78)], sicca symptoms [OR 0.56 (95% CI 0.32, 0.98)] and multimorbidity [Charlson Comorbidity Index; OR 0.81 (95% CI 0.67, 0.97)] were associated with the 'poor' HRQoL LP. CONCLUSION: Distinct HRQoL subgroups exist that are not primarily driven by a specific diagnosis or autoantibody profiles. We identified a number of key demographic and clinical factors associated with poor HRQoL. These factors need to be addressed across the whole CTD spectrum as part of a holistic management approach aimed at improving overall patient outcomes.

Rituximab versus intravenous cyclophosphamide in patients with connective tissue disease-associated interstitial lung disease in the UK (RECITAL): a double-blind, double-dummy, randomised, controlled, phase 2b trial.

BACKGROUND: Rituximab is often used as rescue therapy in interstitial lung disease (ILD) associated with connective tissue disease (CTD), but has not been studied in clinical trials. This study aimed to assess whether rituximab is superior to cyclophosphamide as a treatment for severe or progressive CTD associated ILD. METHODS: We conducted a randomised, double-blind, double-dummy, phase 2b trial to assess the superiority of rituximab compared with cyclophosphamide. Patients aged 18-80 years with severe or progressive ILD related to scleroderma, idiopathic inflammatory myositis, or mixed CTD, recruited across 11 specialist ILD or rheumatology centres in the UK, were randomly assigned (1:1) to receive rituximab (1000 mg at weeks 0 and 2 intravenously) or cyclophosphamide (600 mg/m2 body surface area every 4 weeks intravenously for six doses). The primary endpoint was rate of change in forced vital capacity (FVC) at 24 weeks compared with baseline, analysed using a mixed-effects model with random intercepts, adjusted for baseline FVC and CTD type. Prespecified secondary endpoints reported in this Article were change in FVC at 48 weeks versus baseline; changes from baseline in 6 min walk distance, diffusing capacity of the lung for carbon monoxide (DLCO), physician-assessed global disease activity (GDA) score, and quality-of-life scores on the St George's Respiratory Questionnaire (SGRQ), King's Brief Interstitial Lung Disease (KBILD) questionnaire, and European Quality of Life Five-Dimension (EQ-5D) questionnaire at 24 and 48 weeks; overall survival, progression-free survival, and time to treatment failure; and corticosteroid use. All endpoints were analysed in the modified intention-to-treat population, which comprised all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov (NCT01862926). FINDINGS: Between Dec 1, 2014, and March 31, 2020, we screened 145 participants, of whom 101 participants were randomly allocated: 50 (50%) to receive cyclophosphamide and 51 (50%) to receive rituximab. 48 (96%) participants in the cyclophosphamide group and 49 (96%) in the rituximab group received at least one dose of treatment and were included in analyses; 43 (86%) participants in the cyclophosphamide group and 42 (82%) participants in the rituximab group completed 24 weeks of treatment and follow-up. At 24 weeks, FVC was improved from baseline in both the cyclophosphamide group (unadjusted mean increase 99 mL [SD 329]) and the rituximab group (97 mL [234]); in the adjusted mixed-effects model, the difference in the primary endpoint at 24 weeks was -40 mL (95% CI -153 to 74; p=0·49) between the rituximab group and the cyclophosphamide group. KBILD quality-of-life scores were improved at 24 weeks by a mean 9·4 points (SD 20·8) in the cyclophosphamide group and 8·8 points (17·0) in the rituximab group. No significant differences in secondary endpoints were identified between the treatment groups, with the exception of change in GDA score at week 48, which favoured cyclophosphamide (difference 0·90 [95% CI 0·11 to 1·68]). Improvements in lung function and respiratory-related quality-of-life measures were observed in both treatment groups. Lower corticosteroid exposure over 48 weeks of follow-up was recorded in the rituximab group. Two (4%) of 48 participants who received cyclophosphamide and three (6%) of 49 who received rituximab died during the study, all due to complications of CTD or ILD. Overall survival, progression-free survival, and time to treatment failure did not significantly differ between the two groups. All participants reported at least one adverse event during the study. Numerically fewer adverse events were reported by participants receiving rituximab (445 events) than those receiving cyclophosphamide (646 events). Gastrointestinal and respiratory disorders were the most commonly reported adverse events in both groups. There were 62 serious adverse events of which 33 occurred in the cyclophosphamide group and 29 in the rituximab group. INTERPRETATION: Rituximab was not superior to cyclophosphamide to treat patients with CTD-ILD, although participants in both treatment groups had increased FVC at 24 weeks, in addition to clinically important improvements in patient-reported quality of life. Rituximab was associated with fewer adverse events. Rituximab should be considered as a therapeutic alternative to cyclophosphamide in individuals with CTD-ILD requiring intravenous therapy. FUNDING: Efficacy and Mechanism Evaluation Programme (Medical Research Council and National Institute for Health Research, UK).

Multiparametric autoantibody analysis: a new paradigm for the diagnosis of connective tissue diseases.

BACKGROUND: In patients affected by connective tissue diseases (CTDs), the identification of wide autoantibody profiles may prove useful in early diagnosis, in the evaluation of prognosis (risk stratification), and in predicting response to therapy. The aim of the present study was to evaluate the utility of multiparametric autoantibody analysis performed by a new fully automated particle-based multi-analyte technology (PMAT) digital system in a large multicenter cohort of CTD patients and controls. METHODS: Serum samples from 787 patients with CTD (166 systemic lupus erythematosus; 133 systemic sclerosis; 279 Sjögren's syndrome; 106 idiopathic inflammatory myopathies; 103 undifferentiated CTD), 339 patients with other disorders (disease controls) (118 infectious diseases, 110 organ-specific autoimmune diseases, 111 other rheumatic diseases), and 121 healthy subjects were collected in 13 rheumatologic centers of the FIRMA group. Sera were analyzed with the Aptiva-PMAT instrument (Inova Diagnostics) for a panel of 29 autoantibodies. RESULTS: Multiparametric logistic regression showed that enlarged antibody profiles have a higher diagnostic efficiency than that of individual antibodies or of antibodies that constitute classification criteria for a given disease and that probability of disease increases with multiple positive autoantibodies. CONCLUSIONS: This is the first study that analyzes the clinical and diagnostic impact of autoantibody profiling in CTD. The results obtained with the new Aptiva-PMAT method may open interesting perspectives in the diagnosis and sub-classification of patients with autoimmune rheumatic diseases.

Intravenous infusion of mesenchymal stem cells for refractory systemic sclerosis management: TWo-year follow-up

Systemic sclerosis is an autoimmune disease whose etiology remains unknown. Some patients prove refractory and require other therapies. Recently, the use of mesenchymal stem cells (MSC) for the treatment of disease refractory to conventional treatments has been considered. We present a case of refractory systemic sclerosis; Wharton's jelly mesenchymal stem cell was given in response. Decrease in perioral wrinkles, reduced telangiectasia and decrease in modified Rodnan skin score were observed two years later. A decrease in brain natriuretic peptide and improved pulmonary function were also found. And improvement of pulmonary fibrosis on high resolution tomography and capillaroscopy changes. In conclusion, MSC infusion seems to be effective and safe treatment of refractory scleroderma

La esclerosis sistémica es una enfermedad autoinmune de etiología desconocida y difícil manejo. Algunos casos que se tornan refractarios requieren terapias alternativas, como las células madre mesenquimales (MSC). Presentamos un caso de esclerosis sistémica refractaria que se llevó a terapia con MSC de gelatina de Wharton. Tras dos años, se observó ∗ Corresponding disminución en arrugas peribucales, aumento en apertura bucal, reducción de telangiectasias y en Rodnan modificado. También hubo disminución del péptido natriurético cerebral y mejora de pruebas de función pulmonar desde los seis meses de seguimiento, con mejoría en fibrosis pulmonar en tomografía de alta resolución y cambios en la capilaroscopia. En conclusión, el tratamiento con infusión de MSC parece efectivo y seguro en esclerosis sistémica refractaria.

Study on syndrome rules of stagnated heat in liver and stomach of non-erosive reflux disease based on microecology of tongue coating.

INTRODUCTION: At present, the pathogenesis of non-erosive reflux disease (NERD) is still unclear, and proton pump inhibitors are the main treatment drug. However, the effect is limited. Traditional Chinese medicine treatment of NERD has advantages. Stagnated heat in liver and stomach syndrome is the most important traditional Chinese medicine syndrome type of this disease. Tongue diagnosis is an important basis for the diagnosis of stagnated heat in liver and stomach syndrome. The microecology of tongue coating suggests the occurrence and development of disease. The purpose of this study aims to clarify the regular changes of tongue coating microecology in stagnated heat in liver and stomach syndrome of NERD. METHODS AND ANALYSIS: This is a cross-sectional clinical trial. This study is divided into NERD stagnated heat in liver and stomach syndrome group, qi stagnation, and phlegm obstruction syndrome control group and normal control group, with 20 cases in each group. Tongue coating samples will be collected from 3 groups, and 16SrRNA gene sequencing technology will be used to detect the genome of tongue coating flora in patients with NERD with stagnated heat in liver and stomach syndrome, control group with qi stagnation and phlegm obstruction syndrome and normal control group. The main outcome measures are the distribution, diversity, and richness of the tongue flora in patients and healthy controls. DISCUSSION: The results of this study will clarify the internal relationship between NERD stagnated heat in liver and stomach syndrome and the microecological changes in tongue coating.

Association between vitamin D deficiency and disease activity in Paraguayan patients with systemic lupus erythematosus / Asociación entre la deficiencia de vitamina D y la actividad de la enfermedad en pacientes paraguayos con lupus eritematoso sistémico

ABSTRACT Objective: To identify the association between vitamin D (VD) concentrations and the activity of systemic lupus erythematosus (SLE) and determine a supplementation dose that allows patients to maintain adequate levels of VD. Methods: Longitudinal, observational study. Serum levels of 25-hydroxy-VD were measured in 100 Paraguayan SLE patients from the Hospital de Clínicas between 2016 and 2018. To analyze the response to different doses of VD supplementation, 50 patients received 1000IU/day and the other 50 patients received 2000IU. SLE disease activity measured by SELENA-SLEDAIwas scored before and after supplementation. Results: The mean age was 27.5 ±9.8 years, 88.9% of patients presented mild disease activ ity and 11.1% presented moderate to severe activity. The mean VD concentration was 30.8 ± 11.8 ng/mL. A total of 34% of patients presented VD insufficiency and 13% VD defi ciency. There was an inverse relationship between VD concentrations and SLE disease activity (p = 0.03). Increasing levels of serum VD are associated with supplementation of 2000 IU/day (p = 0.0224). Conclusion: SLE activity was associated with low levels of VD. In our cohort, SLE patients required a supplementation dose equal to or greater than 2000 IU/day to increase their serum VD.

R E S U M E N Objetivo: Identificar la asociación entre las concentraciones de vitamina D (VD) y la actividad del lupus eritematoso sistémico (LES), además de encontrar una dosis de suplementación que les permita a los pacientes mantener niveles adecuados de VD. Métodos: Estudio observacional longitudinal. Se midieron los niveles séricos de 25-hidroxi-VD en 100 pacientes paraguayos con LES, del Hospital de Clínicas, entre los años 2016 y 2018. Para analizar la respuesta a diferentes dosis de suplementación con VD, 50 pacientes recibieron 1.000 UI/día y los otros 50 pacientes recibieron 2.000 UI/día. La actividad de la enfermedad del LES medida por SELENA-SLEDAI se puntuó antes y después de la suplementación. Resultados: La media de edad fue de 27,5 ± 9,8 años, el 88,9% de los pacientes presentó actividad leve de la enfermedad y el 11,1% presentó actividad moderada a severa. La concentración media de VD fue de 30,8 ± 11,8 ng/ml. El 34% de los pacientes presentó insuficiencia de VD y el 13%, deficiencia de VD. Hubo una relación inversa entre las concentraciones de VD y la actividad de la enfermedad del LES (p = 0,03). Los niveles crecientes de VD en suero se asocian con una suplementación de 2.000 UI/día (p = 0,0224). Conclusión: La actividad del LES se asoció con niveles bajos de VD. En nuestra cohorte, los pacientes con LES requirieron una dosis de suplementación igual o superior a 2.000 UI/día para aumentar su VD sérica.

The mechanism of triptolide in the treatment of connective tissue disease-related interstitial lung disease based on network pharmacology and molecular docking.

BACKGROUND: Interstitial lung disease (ILD) is associated with substantial morbidity and mortality, which is one of the key systematic manifestations of connective tissue disease (CTD). Tripterygium wilfordii, known as Leigongteng in Chinese, has been applied to treat connective tissue disease-related interstitial lung disease (CTD-ILD) for many years. Triptolide is a key effective component from Tripterygium wilfordii. But the molecular mechanism of Triptolide for treating CTD-ILD is not yet clear. METHODS: Gaining insight into the molecular mechanism of Triptolide intervention CTD-ILD, we used the method of network pharmacology. And then we conducted drug-target networks to analyse the potential protein targets between Triptolide and CTD-ILD. Finally, AutoDock Vina was selected for molecular docking. RESULTS: By analysing the interaction genes between Triptolide and CTD-ILD, 242 genes were obtained. The top 10 targets of the highest enrichment scores were STAT3, AKT1, MAPK1, IL6, TP53, MAPK3, RELA, TNF, JUN, JAK2. GO and KEGG enrichment analysis exhibited that multiple signalling pathways were involved. PI3K-Akt, multiple virus infections, cancer signalling, chemokine, and apoptosis signalling pathway are the main pathways for Triptolide intervention CTD-ILD. And it is related to various biological processes such as inflammation, infection, cell apoptosis, and cancer. Molecular docking shows Triptolide can bind with its target protein in a good bond by intermolecular force. CONCLUSIONS: This study preliminarily reveals the internal molecular mechanism of Triptolide interfere with CTD-ILD through multiple targets, multiple access, validated through molecular docking.KEY MESSAGESTriptolide intervention CTD-ILD, which are related to various biological processes such as inflammation, infection, cell apoptosis, and cancer.PI3K-Akt, multiple virus infections, and apoptosis signalling pathway are the main pathways for Triptolide intervention CTD-ILD.Triptolide can bind with related target protein in a good bond by Intermolecular force, exhibiting a good docking activity.

Nutrition and connective tissue disease.

Despite an incomplete overall understanding, nutrition plays an important role in connective tissue disease. Assessment of patients with connective tissue disease for nutritional status and metabolic disturbances may significantly contribute to patient outcomes. Several studies have indicated the multifactorial role of macronutrients, micronutrients, and supplements in the setting of connective tissue disease. There is additional evidence regarding the roles of weight, obesity, and malnutrition. This contribution reviews a growing body of data regarding nutrition in the development and treatment of various connective tissue diseases, including systemic lupus erythematosus, dermatomyositis, and systemic sclerosis.

Osteoporosis and osteonecrosis in systemic lupus erythematosus / Osteoporosis y osteonecrosis en el lupus eritematoso sistémico

ABSTRACT Half of the patients with systemic lupus erythematosus (SLE) will have a reduced bone density and more than one in ten will develop osteoporosis (OP) prematurely. Multiple risk factors have been related to loss of bone mass, but just a few are modifiable, such as adequate vitamin D and calcium intakes, weight bearing exercise, controlling SLE activity and limiting the use of glucocorticoids (GC). GC have also been strongly associated to osteonecrosis or avascular necrosis (AVN). The main consequences of OP and AVN are fractures, which lead to significant functional limitation, loss of quality of life and increased morbidity. OP-related fractures can be reduced by performing appropriate screening with bone densitometries and providing prophylactic treatment when long-term or high dose GC are needed. No formal screening is available for AVN; but diagnosis is made by imaging (X-ray, bone scan or advanced imaging where appropriate). Aiming for the lowest dose possible of GC in combination with immunosuppression as well as an early recognition of the symptoms will prevent further complications. This manuscript is a practical review of the epidemiology, pathophysiology, and management of OP and AVN in patients with SLE, based on the available evidence and guidelines.

RESUMEN La mitad de los pacientes con lupus eritematoso sistémico (LES) tendrá una densidad ósea disminuida, y más de uno de cada 10 desarrollará osteoporosis (OP) prematuramente. Son múltiples los factores de riesgo que se han relacionado con la pérdida de la masa ósea, pero solo unos pocos son modificables, tales como la ingesta de niveles adecuados de vitamina D y de calcio, ejercicio con pesas, controlar la actividad del LES, y limitar el uso de glucocorticoides (GC). También se ha encontrado una estrecha relación entre el uso de GC y osteonecrosis o a necrosis avascular (NAV). Las principales consecuencias de la OP y de la NAV son fracturas, que generan una limitación funcional importante, pérdida de la calidad de vida y aumento de la morbilidad. Las fracturas por osteoporosis se pueden reducir mediante un tamizaje adecuado con densitometría ósea y administrando tratamiento profiláctico cuando se requieren GC de largo plazo o a altas dosis. No existe un tamizaje formal para la NAV, pero su diagnóstico se realiza con imágenes (radiografía, gammagrafía ósea o imágenes avanzadas cuando corresponda). El apuntar a la menor dosis posible de GC, en combinación con inmunosupresión, además de la temprana identificación de los síntomas, ayudará a prevenir otras complicaciones. El presente artículo es una revisión práctica de la epidemiología, la fisiopatología y el manejo de la OP y la NAV en pacientes con LES, en función de la evidencia y de las guías disponibles.

Cleft palate morphology, genetic etiology, and risk of mortality in infants with Robin sequence.

Robin sequence (RS) has many genetic and nongenetic causes, including isolated Robin sequence (iRS), Stickler syndrome (SS), and other syndromes (SyndRS). The purpose of this study was to determine if the presence and type of cleft palate varies between etiologic groups. A secondary endpoint was to determine the relationship of etiologic group, cleft type, and mortality. Retrospective chart review of patients with RS at two high-volume craniofacial centers. 295 patients with RS identified. CP was identified in 97% with iRS, 95% with SS, and 70% of those with SyndRS (p < .0001). U-shaped CP was seen in 86% of iRS, 82% with SS, but only 27% with SyndRS (p < .0001). At one institution, 12 children (6%) with RS died, all from the SyndRS group (p < .0001). All died due to medical comorbidities related to their syndrome. Only 25% of children who died had a U-shaped CP. The most common palatal morphology among those who died was an intact palate. U-shaped CP was most strongly associated with iRS and SS, and with a lower risk of mortality. RS with submucous CP, cleft lip and palate or intact palate was strongly suggestive of an underlying genetic syndrome and higher risk of mortality.

The effect of vitamin D3 and thyroid hormones on the capillaroscopy-confirmed microangiopathy in pediatric patients with a suspicion of systemic connective tissue disease-a single-center experience with Raynaud phenomenon.

Raynaud phenomenon (RP) may be the first manifestation of a systemic connective tissue disease (SCTD). Early detection of dysfunction of small vessels called microangiopathy is essential for the diagnostic process. The focus of this single-center, retrospective study was to investigate the potential dependencies between microvascular image and laboratory markers measured in children with RP. The study analyzed the nail-fold video-capillaroscopy (NVC) findings and laboratory results of 81 children between the ages 6 and 17 who were referred to pediatric rheumatologist with a suspicion of SCTD. Out of 52 patients presenting with RP at the time of evaluation, abnormalities in capillary microscopic imaging were found in 34. NVC findings were then compared to levels of specific biomarkers in serum. Vitamin D3 serum levels have been significantly decreased in patients with RP (23.4 ng/mL ± 8.76 vs. 30.0 ng/mL ± 12.66, P = 0.0148). There were positive significant correlations between levels of vitamin D3 and acute-phase reactants in serum, such as C-reactive protein (P = 0.0292). Furthermore, free thyroxine levels (fT4) in patients with both RP (P = 0.0126) and micro-angiopathy (P = 0.05496) persisted in the lower range of the normal limit (< 1.0 ng/dL). Regular oral supplementation of vitamin D3 should be always considered in children with RP if deficiency is found. Additionally, low fT4 level (< 1.0 ng/dL) should be considered as an indication to perform NVC in patients suspected of SCTD even when they do not present RP.

Periodontal Comparison on Systemic Lupus Erythematosus Patients and Healthy Subjects: A Cross-Sectional Study

ABSTRACT Objective: To analyze periodontal comparison between Systemic Lupus Erythematosus (SLE) subject and healthy control. Material and Methods: This descriptive cross-sectional study included 122 subjects, 61 SLE patients and 61 healthy subjects who visited the Rheumatology Department, Dr. Saiful Anwar General Hospital, Malang, during 2017-2018. Clinical examination of SLE was using Mexican SLE Disease Activity Index and oral cavity conditions were assessed using the periodontal index, gingival index, calculus index, bleeding on probing, clinical attachment loss and mobility teeth. Results: The age of SLE patients ranged from 18-55 years old with the mean age of 29.50 ± 9.57 years old. Periodontitis was higher in SLE patients (88.5%) than healthy subjects (22.95%). In addition, periodontitis occurrence in SLE (2.66 ± 1.02) was significantly different (p<0.001) compared to healthy subjects (0.51 ± 0.81). Conclusion: This study found higher rates of periodontitis, gingivitis, bleeding on probing, clinical attachment loss, and mobility tooth among SLE patients compared to healthy subjects. Periodontitis was also found to be higher along with more severe SLE group.

A novel deep intronic COL2A1 mutation in a family with early-onset high myopia/ocular-only Stickler syndrome.

PURPOSE: To identify the genetic defect causing early-onset high myopia (eoHM)/ocular-only Stickler syndrome (ocular-STL) in a large Chinese family. METHODS: Genomic DNA and clinical data from a four-generation family with eoHM/ocular-STL were collected. Whole-exome sequencing was performed on one affected member in initial screening. Linkage scan based on microsatellite markers was carried out initially from candidate loci associated with autosomal dominant eoHM and Stickler syndrome. Sanger sequencing was used to detect potential variants. The pathogenicity of candidate variants was evaluated using mini genes ex vivo. RESULTS: Eight patients and five unaffected members in the family participated in the study, in which the patients had high myopia with other variable ocular phenotypes but without extraocular abnormalities. Whole exome sequencing did not detect any potential pathogenic variant in all genes known to associate with the disease. The eoHM/ocular-STL in the family was mapped to markers around COL2A1 by candidate loci linkage scan, with a maximum lod score of 3.31 for D12S1590 at θ = 0. A novel deep intronic variant, c.86-50C > G in intron 1 of COL2A1, was detected by Sanger sequencing and co-segregated with eoHM/ocular-STL in the family. Ex vivo splicing test using mini genes confirmed that the variant created a new splicing acceptor 49 bp before the canonical splicing site of exon 2, resulted in addition of 49 bp fragment in the transcript (from c.86-49 to c.86-1) and premature termination. CONCLUSIONS: Linkage study, bioinformatics prediction, and ex vivo transcript analysis suggest a novel deep intronic variant adjacent to 5-prime of exon 2 of COL2A1, affecting exon 2 splicing, as a potential cause of ocular-STL in a large family. To our knowledge, this is the first report of an intronic variant around exon 2 as a cause of ocular-STL while a series of variants in the coding region of exon 2, a dispensable alternative-splicing exon for extraocular tissues, in COL2A1 have been reported to cause Stickler syndrome-related ocular phenotype alone.

Observation using thermography of post-operative reaction after fascial manipulation®.

INTRODUCTION AND OBJECTIVE: Fascia Manipulation® is one of the methods focusing on the deep fascia. The assumption is that fascial manipulation is carried out on precisely determined points - coordination centres (cc), and on a limited area so as the friction occurring during manipulation would cause a local rise in temperature due to the inflammatory reaction. Rise in temperature influences modification in consistency of elementary matter in the manipulated area, and by the same token causing a decrease in the negative effects of fascia densification which stems from accumulation of hyaluronic acid. The purpose of the research is to prove the thesis that fascial manipulation causes local rise in temperature due to inflammatory reaction. MATERIAL AND METHODS: For the research, 25 individuals with densification in lower limb area were qualified. They were exposed to a single, 3-minute facial manipulation®. By means of a thermal-imaging camera, changes in the temperature of the body in the examined area were evaluated. The body's temperature evaluation was carried out 8 times: before the treatment, 5 minutes after the treatment, and, next, 6, 12, 18, 24, 36, 48 hours after the treatment. RESULTS: The average surface temperature of the treated area before mobilization was 33.4°C. A statistically relevant increase in temperature was already observed 5 minutes after the treatment (increase of 0.5°C; p<0.001). However, the highest temperature was observed 24 hours after mobilization (increase of 2.4°C). The difference between the first and 7 other measurements was statistically relevant (p<0.001). CONCLUSIONS: The statistically relevant increase in temperature under the influence of fascial manipulation® in the treatment area can confirm the occurrence of inflammatory reaction.

Vasculopatia livedoide tratada com rivaroxabana / Livedoid vasculopathy treated with rivaroxaban

A vasculopatia livedoide é uma doença rara caracterizada pela oclusão da microvasculatura da derme, originando lesões maculosas que, posteriormente, podem evoluir para úlceras e cicatrizes atróficas. Como um fenômeno vaso-oclusivo, o tratamento geralmente é realizado com antiplaquetários e fibrinolíticos. O presente relato descreve o caso de uma paciente refratária à terapia convencional, que obteve regressão da doença utilizando a rivaroxabana, um fármaco inibidor seletivo do fator Xa. (AU)

Livedoid vasculopathy is a rare disease characterized by occlusion of the dermis microvasculature, leading to spotted lesions that can later develop into ulcers and atrophic scars. As a vaso- occlusive phenomenon, treatment is usually performed with antiplatelet and fibrinolytic agents. The present report describes the case of a female patient refractory to conventional therapy who presented disease remission using rivaroxaban, a selective factor Xa inhibitor drug. (AU)

Antibody responses to influenza vaccine in patients on biological therapy: Results of RIER cohort study.

BACKGROUND AND OBJECTIVES: Influenza vaccine is recommended for patients with autoimmune inflammatory rheumatic diseases who receive biological therapy. To evaluate if biological therapy impairs immunization after seasonal influenza vaccine. MATERIAL AND METHODS: Patients with inflammatory arthopathies, psoriasis, inflammatory bowel disease or connective tissue diseases who were receiving or were going to initiate biological therapy were included and vaccinated during 2014-2015 influenza season. ELISA was used to measure influenza antigen A and B antibodies, before and after vaccination. Demographic parameters, diagnosis and kind of treatment were recorded and their influence on the final serological status against influenza was studied. RESULTS: 253 subjects were analyzed. After vaccination, 77% of participants presented detectable antibodies against antigen A and 50.6% of them had detectable antibodies against antigen B. Final seropositivity rate against antigen B antibodies increased from baseline (50.6% vs 43.5%, p<0.001). Anti-TNF drugs were associated with better response and rituximab with the worst (79.2% vs 55.0% for final seropositivity against antigen A, p=0.020). Vaccine response in the rituximab group tended to improve when the interval between the drug administration and the vaccination was at least 12 weeks (seropositivity rate 80.0% in those with the longer interval vs 25.0% in the other group, p=0.054). CONCLUSIONS: Among the patients on biological therapy vaccinated against influenza, anti-TNF therapy was identified as a predictive factor of final seropositivity. Rituximab presented a lower rate of final seropositivity, which could be increased with an accurate administration schedule.

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) demonstrates distinct autoimmune and autoinflammatory disease associations according to the adjuvant subtype: Insights from an analysis of 500 cases.

BACKGROUND: We investigated the pattern of reported immune diseases in the international ASIA syndrome registry. METHODS: Data from 500 subjects exposed to adjuvants from the ASIA syndrome international registry were analysed. RESULTS: The patient mean age was 43 ±â€¯17 years and 89% were female. Within the reported immune diseases, 69% were well-defined immune diseases (autoimmune, autoinflammation, and mixed pattern diseases). Among the well-defined immune diseases following the exposure to adjuvants, polygenic autoimmune diseases were significantly higher than autoinflammatory disorders (92.7% vs 5.8%, respectively, p < 0.001). Polygenic autoimmune diseases such as connective tissue diseases were significantly linked to the exposure to HBV vaccine (OR 3.15 [95%CI 1.08-9.23], p = 0.036). Polygenic autoinflammatory diseases were significantly associated with the exposure to influenza vaccination (OR 10.98 [95%CI 3.81-31.67], p < 0.0001). CONCLUSIONS: Immune conditions following vaccination are rare, and among these, polygenic autoimmune diseases represent the vast majority of the well-defined immune diseases reported under the umbrella ASIA syndrome. However, vaccines benefit outweighs their autoimmune side effects.

"Semenly" Harmless Back Pain: An Unusual Presentation of a Subcutaneous Abscess

Aims We report, with review of the literature, the case of a patient who developed a subcutaneous abscess after intravenously injecting his own semen in an attempt to treat longstanding back pain. He had devised this "cure" independent of medical advice. Methods A review of EMBASE, PubMed, google scholar and the wider internet was conducted with an emphasis on parenteral semen for the treatment of back pain and for other medical and non-medical uses. Results There were no other reported cases of intravenous semen injection found across the medical literature. A broader search of internet sites and forums found no documentation of semen injection for back pain treatment or otherwise. Conclusion While suicide attempt by intravenous injection of harmful substances is well described, this unique case demonstrates risks involved with innovative treatments prior to clinical research in the form of phased trials inclusive of safety and efficacy assessments.