Coagulation and skin autoimmunity

Several lines of evidence indicate that the immune system, inflammation, and coagulation are simultaneously activated in autoimmune and immune-mediated skin diseases. Pro-inflammatory cytokines such as interleukin-6 and tumor necrosis factor-alpha induce the expression of the main initiator of coagulation, i.e., tissue factor. The proteases of coagulation in turn act on protease-activated receptors inducing the expression of various pro-inflammatory cytokines triggering inflammation. The cross-talk among immune system, inflammation, and coagulation amplifies and maintains the activation of all three pathways. This review focuses on three skin disorders as chronic spontaneous urticaria (CSU), angioedema, and bullous pemphigoid (BP), in which the relationships among the three systems have been investigated or their clinical consequences are relevant. Markers of thrombin generation, fibrinolysis, and inflammation have been reported to be increased in the plasma during flares of CSU and angioedema, as well as in the active phase of BP, with the marker levels reverting to normal during remission. The coagulation activation seems to be important only at local level in CSU and angioedema while both at local and systemic levels in BP which is the only condition associated with an increased thrombotic risk. The prothrombotic state in autoimmune skin diseases raises the question of the indication of anticoagulant treatment, particularly in the presence of other cardiovascular risk factors

There is still room for improvement in the completeness of abstract reporting according to the PRISMA-A checklist: a cross-sectional study on systematic reviews in periodontology

Background: To evaluate the completeness of reporting abstracts of systematic reviews (SRs) before and after the publication of the PRISMA-A checklist in 2013 and to assess if an association exists between abstract characteristics and the completeness of reporting. / Methods: A systematic search of the literature was conducted in the PubMed and Scopus databases in March 2020. The search focused on the SRs of evaluations of interventions published since 2002 in the field of periodontology. The abstracts of the selected SRs were divided into two groups before and after publication of the PRISMA-A checklist in 2013, and compliance with the 12 items reported in the checklist was evaluated by three calibrated evaluators. / Results: A set of 265 abstracts was included in the study. The total score before (mean score, 53.78%; 95% CI, 51.56–55.90%) and after (mean score, 56.88%; 95% CI, 55.39–58.44%) the publication of the PRISMA-A statement exhibited a statistically significant improvement (P = 0.012*). Nevertheless, only the checklist items included studies and synthesis of the results displayed a statistically significant change after guideline publication. The total PRISMA-A score was higher in the meta-analysis group and in articles authored by more than four authors. / Conclusions: The impact of the PRISMA-A was statistically significant, but the majority of the items did not improve after its introduction. The editors and referees of periodontal journals should promote adherence to the checklist to improve the quality of the reports and provide readers with better insight into the characteristics of published studies

Development and validation of a mathematical equation to estimate glomerular filtration rate in cirrhosis: The rfh cirrhosis Gfr

Current expressions based on serum creatinine concentration overestimate kidney function in cirrhosis leading to significant differences between "true" and calculated glomerular filtration rate (GFR). We compared the performance of MDRD-4, MDRD-6 and CKD-EPI with "true" GFR and the impact of this difference on MELD calculation. We subsequently developed and validated a GFR equation specifically for cirrhosis and compared the performance of the new derived formula with existing GFR formulas. We included 469 consecutive patients who had a transplant assessment between 2011 and 2014. "True" GFR (mGFR) was measured using plasma isotope clearance according to a technique validated in patients with ascites. A corrected creatinine was derived from the mGFR after application of the MDRD formula. Subsequently, a corrected MELD was calculated and was compared with the conventionally calculated MELD. Stepwise multiple linear regression was used to derive a GFR equation. This was compared with the measured GFR in independent external and internal validation sets of 82 and 174 patients with cirrhosis respectively. A difference>20 ml/min/1.73m(2) between existing formulae and mGFR was observed in 226 (48.2%) patients. The corrected MELD score was ≥3 points higher in 177 (37.7%) patients. The predicted equation derived (R(2) =74·6%) was: GFR=45·9x(creatinine(-0) ·(836) )x(urea(-0) ·(229) )x(INR(-0) ·(113) )x(age(0) ·(129) )x(sodium(0) ·(972) )x1·236(if male)x0·92(if moderate/severe ascites). The model was a good fit and showed the greatest accuracy compared to that of existing formulae. CONCLUSION: We developed and validated a new accurate model for GFR assessment in cirrhosis, the RFH cirrhosis GFR, using readily available variables. This remains to be tested and incorporated in prognostic scores in patients with cirrhosis

The effect of maxillary protraction, with or without rapid palatal expansion, on airway dimensions: A systematic review and meta-analysis

Aim The use of maxillary protraction appliances (MPAs) and Facemask (FM), with or without a rapid maxillary expansion (RME), have become a routine orthopaedic treatment procedure for the treatment of Class III in growing individuals; several authors have suggested that maxillary protraction could have a positive impact on airway dimensions. The purpose of this systematic review and meta- analysis was to assess the efficacy of maxillary protraction appliances (MPAs), with or without a rapid maxillary expansion (RME), on airway dimensions in children in mixed or early permanent dentition. Methods An electronic search was performed on PubMed, Medline, Scopus, The Cochrane Library, EMBASE and the System for Information on Grey Literature in Europe until November 30th, 2019. The Newcastle-Ottawa (NOS) scale was used to assess the studies’ quality. Review Manager 5.3 (provided by the Cochrane Collaboration) was used to synthesize the effects on airway dimensions. Results After full text assessment, 8 studies were included in the qualitative and quantitative synthesis. NOS scores ranged 6 to 9 indicating high quality. The effects of two therapeutic protocols were compared, treatment with MPAs only (113 subjects treated - 65 controls) and the treatment with MPAs + RME (137 subjects treated-87 controls). The MPAs only treatment group displayed a significantly increase in nasopharyngeal airway dimension at PNS-AD1 (random: mean difference, 1.39 mm, 95% CI, 0.32 mm, 2.47 mm, p= 0.01) and at PNS-AD2 (random: mean difference, 1.70 mm, 95% CI, 1.14 mm, 2.26 mm, p= 0.00001). No statistically significant changes were found post treatment in MPAs + RME treatment groups at PNS-AD1 (P= 0.15), PNS-AD2 (P= 0.17), McNamara’s upper pharynx (MPAs + RME P= 0.05, MPAs P= 0.99) and McNamara lower pharynx (MPAs + RME P= 0.25, MPAs P= 0.40). Conclusion MPAs only treatment can increase the pharyngeal thickness after treatment both at PNS-A1 and PNS-AD2. MPA+ RME had no effect on sagittal widths compared with controls, but the effect on the transverse dimension could not be assessed

Bacterial Infections Change Natural History of Cirrhosis Irrespective of Liver Disease Severity

OBJECTIVES: We assessed the prognostic significance of infections in relation to current prognostic scores and explored if infection could be considered per se a distinct clinical stage in the natural history of cirrhosis. METHODS: We included consecutive patients with cirrhosis admitted to a tertiary referral liver unit for at least 48 h over a 2-year period. Diagnosis of infection was based on positive cultures or strict established criteria. We used competing risk analysis and propensity score matching for data analysis. RESULTS: 501 patients (63% male, 48% alcoholic liver disease, median Model of End-stage Liver Disease (MELD)=17) underwent 781 admissions over the study period. Portal hypertensive bleeding and complicated ascites were the commonest reasons of admission. The incidence of proven bacterial infection was 25.6% (60% community acquired and 40% nosocomial). Survival rates at 3, 6, 12, and 30 months were 83%, 77%, 71%, and 62% in patients without diagnosis of infection, vs. 50%, 46%, 41%, and 34% in patients with diagnosis of infection. Overall survival was independently associated with MELD score (hazards ratio (HR) 1.099), intensive care (ITU) stay (HR 1.967) and bacterial infection (HR 2.226). Bacterial infection was an independent predictor of survival even when patients who died within the first 30 days were excluded from the analysis in Cox regression (HR 2.013) and competing risk Cox models in all patients (HR 1.46) and propensity risk score-matched infected and non-infected patients (HR 1.67). CONCLUSIONS: Infection most likely represents a distinct prognostic stage of cirrhosis, which affects survival irrespective of disease severity, even after recovery from the infective episode

Altered keratinization and vitamin D metabolism may be key pathogenetic pathways in syndromic hidradenitis suppurativa: a novel whole exome sequencing approach

Background: Diagnosis of pyoderma gangrenosum, acne and hidradenitis suppurativa (PASH) and pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PAPASH) patients, in spite of recently identified genetic variations, is just clinical, since most patients do not share the same mutations, and the mutations themselves are not informative of the biological pathways commonly disrupted in these patients. Objective: To reveal genetic changes more closely related to PASH and PAPASH etiopathogenesis, identifying novel common pathways involved in these diseases. Methods: Cohort study on PASH (n = 4) and PAPASH (n = 1) patients conducted using whole exome sequencing (WES) approach and a novel bioinformatic pipeline aimed at discovering potentially candidate genes selected from density mutations and involved in pathways relevant to the disease. Results: WES results showed that patients presented 90 genes carrying mutations with deleterious and/or damage impact: 12 genes were in common among the 5 patients and bared 237 ns ExonVar (54 and 183 in homozygosis and heterozygosis, respectively). In the pathway enrichment analysis, only 10 genes were included, allowing us to retrieve 4 pathways shared by all patients: (1) Vitamin D metabolism, (2) keratinization, (3) formation of the cornified envelope and (4) steroid metabolism. Interestingly, all patients had vitamin D levels lower than normal, with a mean value of 10 ng/mL. Conclusion: Our findings, through a novel strategy for analysing the genetic background of syndromic HS patients, suggested that vitamin D metabolism dysfunctions seem to be crucial in PASH and PAPASH pathogenesis. Based on low vitamin D serum levels, its supplementation is envisaged

Bibliometric analysis in paediatric dental journals listed in journal citation reports. Current trends

Aim The aim of this study was to analyse articles published in paediatric dental journals included in Journal Citation Reports (JCR), to determine current trends in paediatric publishing. Methods Articles included in paediatric dentistry journals in 2020 JCR were selected, published during the period 2008– 2020. After applying inclusion criteria, author-based parameters (article title, first author’s name, institution, sex and number of authors, number of affiliations, first/last author’s origin and geographic origin), and article-based parameters (article type, main topic, research design) were registered for each article. Results A total of 3,027 articles were analysed. The percentage of female authors showed an increasing positive tendency over the decade and the top producing country was the USA (16.5%). Dental surgery was the most recurrent topic (23.4%). Regarding the origin of the first author’s affiliation, 51% proceeded from the paediatric dentistry departments belonging to public institutions, with a decreasing trend in non-academic/ private affiliations. Positive and negative correlations exist between citation count and other variables. Conclusions International Journal of Paediatric Dentistry, Journal of Clinical Pediatric Dentistry, European Journal of Paediatric Dentistry and Pediatric Dentistry were the four main journals in terms of production volume, USA being the most productive country. The most recurrent topic was dental surgery, and the most common design was observational studies. Study design, geographic origin of the articles, article type and main subject of the article might predict citation.Odontologí

MicroRNA-21 Expression as a Prognostic Biomarker in Oral Cancer: Systematic Review and Meta-Analysis

Oral carcinoma represents one of the main carcinomas of the head and neck region, with a 5-year survival rate of less than 50%. Smoking and tobacco use are recognized risk factors. Prognostic survival biomarkers can be a valid tool for assessing a patient’s life expectancy and directing therapy towards specific targets. Among the biomarkers, the alteration of miR-21 expression in tumor tissues is increasingly reported as a valid prognostic biomarker of survival for oral cancer. The purpose of this meta-analysis was, therefore, to investigate and summarize the results in the literature concerning the potential prognostic expression of tissue miR-21 in patients with OSCC. Methods: The systematic review was conducted following the PRISMA guidelines using electronic databases, such as PubMed, Scopus, and the Cochrane Central Register of Controlled Trials, with the use of combinations of keywords, such as miR-21 AND oral cancer, microRNA AND oral cancer, and miR-21. The meta-analysis was performed using the RevMan 5.41 software. Results: At the end of the article-selection process, 10 studies were included in the meta-analysis, and the result for the main outcome was a pooled HR per overall survival (OS) of 1.29 (1.16–1.44) between high and low expression of miR-21. Conclusions: The data in the literature and the results emerging from the systematic review indicate that miR-21 can provide a prognostic indication in oral cancer

The Prognostic Role of miR-31 in Head and Neck Squamous Cell Carcinoma: Systematic Review and Meta-Analysis with Trial Sequential Analysis

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide with high recurrence, metastasis, and poor treatment outcome. Prognostic survival biomarkers can be a valid tool for assessing a patient’s life expectancy and directing therapy toward specific targets. Recent studies have reported microRNA (miR) might play a critical role in regulating different types of cancer. The main miR used as a diagnostic and prognostic biomarker and reported in the scientific literature for HNSCC is miR-21. Other miRs have been investigated to a lesser extent (miR-99a, miR-99b, miR-100, miR-143, miR-155, miR-7, miR-424, miR-183), but among these, the one that has attracted major interest is the miR-31. Methods: The systematic review was conducted following the PRISMA guidelines using electronic databases, such as PubMed, Scopus, and the Cochrane Central Register of Controlled Trials, with the use of combinations of keywords, such as miR-31 AND HNSCC, microRNA AND HNSCC, and miR-31. The meta-analysis was performed using the RevMan 5.41 software (Cochrane Collaboration, Copenhagen, Denmark). Results: This search produced 721 records, which, after the elimination of duplicates and the application of the inclusion and exclusion criteria, led to 4 articles. The meta-analysis was conducted by applying fixed-effects models, given the low rate of heterogeneity (I2 = 40%). The results of the meta-analysis report an aggregate hazard ratio (HR) for the overall survival (OS), between the highest and lowest miR-31 expression, of 1.59, with the relative intervals of confidence (1.22 2.07). Heterogeneity was evaluated through Chi2 = 5.04 df = 3 (p = 0.17) and the Higgins index I2 = 40; testing for the overall effect was Z = 3.44 (p = 0.00006). The forest plot shows us a worsening HR value of OS, in relation to the elevated expression of miR-31. Conclusions: In conclusion, the data resulting from the current meta-analysis suggest that miR-31 is associated with the prognosis of patients with HNSCC and that elevated miR-31 expression could predict a poor prognosis in patients with this type of neoplasm

Paradoxical Skin Reactions to Biologics in Patients With Rheumatologic Disorders

Targeted immune-modulating treatment with biological agents has revolutionized the management of immune-mediated inflammatory diseases, including rheumatologic conditions. The efficacy and tolerability of biological agents, from the initial tumour necrosis factor (TNF)-\u3b1 inhibitors to the new anti-cytokine monoclonal antibodies, have dramatically changed the natural history of debilitating conditions such as rheumatoid arthritis and seronegative spondyloarthropathies. The widening use of biologics across several rheumatologic diseases has been associated with a new class of adverse events, the so-called paradoxical reactions. These events are inflammatory immune-mediated tissue reactions, developing paradoxically during treatment of rheumatologic conditions with targeted biologics that are commonly used for treating the idiopathic counterparts of these drug-induced reactions. The skin is frequently involved, and, even if considered rare to uncommon, these cutaneous manifestations are an important cause of biologic agent discontinuation. TNF-\u3b1 antagonist-induced psoriasis, which can manifest de novo or as exacerbation of a pre-existing form, is the prototypic and most frequent paradoxical skin reaction to biologics while other reactions, such as eczematous and lichenoid eruptions, hidradenitis suppurativa, pyoderma gangrenosum, Sweet's syndrome and granulomatous skin diseases, occur much more rarely. Management of these reactions consists of topical or systemic skin-directed therapies, depending on the severity and extension of the cutaneous picture, and it is generally associated with switching over to other disease-modifying regimens for treating the underlying rheumatologic condition. Here, we review in detail the current concepts and controversies on classification, pathogenesis and clinical management of this new class of cutaneous adverse events induced by biologics in rheumatologic patients