Clinical perspectives on sampling and processing approaches for the management of infection in diabetic foot ulceration: A qualitative study.

Diabetic foot ulcers (DFUs) often become infected and are treated with antimicrobials, with samples collected to inform care. Swab samples are easier than tissue sampling but report fewer organisms. Compared with culture and sensitivity (C&S) methods, molecular microbiology identifies more organisms. Clinician perspectives on sampling and processing are unknown. We explored clinician perspectives on DFU sampling-tissue samples/wound swabs-and on processing techniques, culture and sensitivity or molecular techniques. The latter provides information on organisms which have not survived transport to the laboratory for culture. We solicited feedback on molecular microbiology reports. Qualitative study using semi-structured interview, with analysis using a Framework approach. CODIFI2 clinicians from UK DFU clinics. Seven consultants agreed to take part. They reported, overall, a preference for tissue samples over swabbing. Clinicians were not confident replacing C&S with molecular microbiology as the approach to reporting was unfamiliar. The study was small and did not recruit any podiatrists or nurses, who may have discipline-specific attitudes or perspectives on DFU care. Both sampling approaches appear to be used by clinicians. Molecular microbiology reports would not be, at present, suitable for replacement of traditional culture and sensitivity.

The National Conference on Health Disparities Student Research Forum.

The annual National Conference on Health Disparities (NCHD) was launched in 2000. It unites health professionals, researchers, community leaders, and government officials, and is a catalyzing force in developing policies, research interventions, and programs that address prevention, social determinants, health disparities, and health equity. The NCHD Student Research Forum (SRF) was established in 2011 at the Medical University of South Carolina to build high-quality biomedical research presentation capacity in primarily underrepresented undergraduate and graduate/professional students. This paper describes the unique research training and professional development aspects of the NCHD SRF. These include guidance in abstract development, a webinar on presentation techniques and methods, a vibrant student-centric conference, and professional development workshops on finding a mentor and locating scholarship/fellowship funding, networking, and strategies for handling ethical issues in research with mentors. Between 2011 and 2018, 400 undergraduate and graduate/professional students participated in the NCHD SRF. Most students were women (80.5%). Approximately half were African American or black (52.3%), 18.0% were white, and 21.3% were of Hispanic/Latinx ethnicity. The NCHD SRF is unique in several ways. First, it provides detailed instructions on developing a scientific abstract, including content area examples. Second, it establishes a mandatory pre-conference training webinar demonstrating how to prepare a scientific poster. Third, it works with the research mentors, faculty advisors, department chairs, and deans to help identify potential sources of travel funding for students with accepted abstracts. These features make the NCHD SRF different from many other conferences focused on students' scientific presentations.

Incidence trends for twelve cancers in younger adults-a rapid review.

Many cancer referral guidelines use patient's age as a key criterium to decide who should be referred urgently. A recent rise in the incidence of colorectal cancer in younger adults has been described in high-income countries worldwide. Information on other cancers is more limited. The aim of this rapid review was to determine whether other cancers are also increasing in younger age groups, as this may have important implications for prioritising patients for investigation and referral. We searched MEDLINE, Embase and Web of Science for studies describing age-related incidence trends for colorectal, bladder, lung, oesophagus, pancreas, stomach, breast, ovarian, uterine, kidney and laryngeal cancer and myeloma. 'Younger' patients were defined based on NICE guidelines for cancer referral. Ninety-eight studies met the inclusion criteria. Findings show that the incidence of colorectal, breast, kidney, pancreas, uterine cancer is increasing in younger age groups, whilst the incidence of lung, laryngeal and bladder cancer is decreasing. Data for oesophageal, stomach, ovarian cancer and myeloma were inconclusive. Overall, this review provides evidence that some cancers are increasingly being diagnosed in younger age groups, although the mechanisms remain unclear. Cancer investigation and referral guidelines may need updating in light of these trends.

Practice review: Evidence-based and effective management of fatigue in patients with advanced cancer.

BACKGROUND: Fatigue affects most patients living with advanced cancer and is a symptom that healthcare professionals can find difficult to manage. AIM: To provide healthcare professionals with a pragmatic overview of approaches to management of fatigue in patients with advanced cancer that are commonly recommended by guidelines and to evaluate evidence underpinning them. DESIGN: Scoping review methodology was used to determine the strength of evidence supporting use of interventions recommended in management of fatigue in patients with advanced cancer. DATA SOURCES: National or international guidelines were examined if they described the management of fatigue in adult cancer patients and were written within the last 6 years (2015-2021) in English. The Cochrane Database of Systematic Reviews (January 2011-December 2021) was searched for 'cancer' AND 'fatigue' in title, abstract or keywords. A PubMed search was also made. RESULTS: Evidence indicates physical exercise interventions are effective and patients may benefit from energy conservation tactics. Evidence does not support use of psychostimulants such as methylphenidate. Limited data were found on efficacy of corticosteroids, psychological interventions, nutritional intervention, sleep optimization or complementary therapies for management of fatigue in advanced cancer. CONCLUSION: We recommend regular assessment, review and acknowledgement of the impact of fatigue. Exercise and energy conservation should be considered. Pharmacological interventions are not endorsed as a routine approach. Many interventions currently recommended by guidelines are not supported by a robust evidence base and further research on their efficacy is required.

Matrix metalloproteinases in keratoconus - Too much of a good thing?

Keratoconus (KC) is a progressive, early onset, and often bilateral eye condition, in which the cornea gradually weakens and bulges out, and in advanced cases may eventually become cone-shaped. The available evidence suggests that it is a multifactorial disease with environmental and genetic contributions. Matrix Metalloproteinases (MMPs) are a family of 24 zinc-dependent proteases with the ability to degrade collagen and other extracellular matrix (ECM) proteins, which are important components of the cornea. During the past two decades a growing body of literature has accumulated suggesting a link between MMPs and keratoconus. This article aims to summarize the current knowledge on the role of MMPs in the pathogenesis of KC. MMP-driven ECM remodelling is thought to be a necessary step for cornea healing, but a fine balance in the expression of MMPs is essential in maintaining the integrity and transparency of the cornea and for its correct healing, and an imbalance in this tightly regulated process may, in the long term, result in the progressive weakening of the cornea. There is extensive evidence that MMPs are upregulated in the corneal tissue and tears of KC patients, implicating dysregulated proteolysis in KC, with an increase in the level of some MMPs, particularly MMP-1 and MMP-9, confirmed in multiple independent studies. There is also evidence for a causative link between inflammation, which could result from the mechanical trauma due to contact lens wearing or/and eye rubbing, and the increased MMPs production observed in KC. However, the precise role of each MMP in the cornea is still unclear and the mechanisms causing their upregulation are mostly undiscovered. Further studies are required to verify the functional role of specific MMPs in KC development and assess the genetic association between common MMPs variants and risk of KC. As MMPs inhibitors are in development, this information could potentially drive the discovery of new treatments for KC.

A place for precision medicine in bladder cancer: targeting the FGFRs.

Bladder tumors show diverse molecular features and clinical outcome. Muscle-invasive bladder cancer has poor prognosis and novel approaches to systemic therapy are urgently required. Non-muscle-invasive bladder cancer has good prognosis, but high recurrence rate and the requirement for life-long disease monitoring places a major burden on patients and healthcare providers. Studies of tumor tissues from both disease groups have identified frequent alterations of FGFRs, including mutations of FGFR3 and dysregulated expression of FGFR1 and FGFR3 that suggest that these may be valid therapeutic targets. We summarize current understanding of the molecular alterations affecting these receptors in bladder tumors, preclinical studies validating them as therapeutic targets, available FGFR-targeted agents and results from early clinical trials in bladder cancer patients.

An integrated genomic, transcriptional and protein investigation of FGFRL1 as a putative 4p16.3 deletion target in bladder cancer.

Loss of heterozygosity (LOH) of chromosome arm 4p is a common event in bladder and other malignancies. At least three distinct regions of deletion have been identified, but the deletion targets have so far remained elusive. In this study, we have identified a novel region of deletion mapping to 4p16.3 spanning 0-2.1 Mb, in 15% of bladder tumors and 24% of bladder cancer cell lines. FGFRL1, which maps within this region, was investigated as putative deletion target. The retained FGFRL1 allele was not mutated in cell lines and tumors with LOH, although in patients heterozygous for the rs4647930 functional polymorphism, the common allele was preferentially lost in tumor tissue. Epigenetic silencing of the retained allele was also excluded as levels of FGFRL1 mRNA and protein were similar in cell lines and tumors with and without 4p16.3 loss. However, while FGFRL1 protein was moderately expressed in all layers of the normal bladder epithelium, the majority of tumors showed areas of downregulation. Overall, average FGFRL1 protein expression was significantly lower in bladder tumors compared to normal tissue, but downregulation was independent from 4p16.3 LOH status, FGFR3 mutation, and tumor grade and stage. In conclusion, although we found no evidence supporting a "two-hit" inactivation of FGFRL1 in bladder carcinogenesis, the effect of heterozygous deletion coupled with functional polymorphisms, and the role of post-transcriptional downregulation deserves further investigation.

Understanding GPs' referral decisions for younger patients with symptoms of cancer: a qualitative interview study.

BACKGROUND: Cancer incidence increases with age, so some clinical guidelines include patient age as one of the criteria used to decide whether a patient should be referred through the urgent suspected cancer (USC) pathway. Little is known about how strictly GPs adhere to these age criteria and what factors might influence their referral decisions for younger patients. AIM: To understand GPs' clinical decision making for younger patients with concerning symptoms who do not meet the age criteria for USC referral. DESIGN AND SETTING: Qualitative study using in-depth, semi-structured interviews with GPs working in surgeries across England. METHOD: Participants (n = 23) were asked to recall consultations with younger patients with cancer symptoms, describe factors influencing their clinical decisions, and discuss their overall attitude to age thresholds in cancer referral guidelines. A thematic analysis guided by the Framework approach was used to identify recurring themes. RESULTS: GPs' decision making regarding younger patients was influenced by several factors, including personal experiences, patients' views and behaviour, level of clinical concern, and ability to bypass system constraints. GPs weighted potential benefits and harms of a referral outside guidelines both on the patient and the health system. If clinical concern was high, GPs used their knowledge of local systems to ensure patients were investigated promptly even when not meeting the age criteria. CONCLUSION: While most GPs interpret age criteria flexibly and follow their own judgement and experience when making clinical decisions regarding younger patients, system constraints may be a barrier to timely investigation.

Overview on the Link Between the Complement System and Auto-Immune Articular and Pulmonary Disease.

Complement system (CS) dysregulation is a key factor in the pathogenesis of different autoimmune diseases playing a central role in many immune innate and adaptive processes. Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by ta breach of self-tolerance leading to a synovitis and extra-articular manifestations. The CS is activated in RA and seems not only to mediate direct tissue damage but also play a role in the initiation of RA pathogenetic mechanisms through interactions with citrullinated proteins. Interstitial lung disease (ILD) represents the most common extra-articular manifestation that can lead to progressive fibrosis. In this review, we focused on the evidence of CS dysregulation in RA and in ILD, and highlighted the role of the CS in both the innate and adaptive immune responses in the development of diseases, by using idiopathic pulmonary fibrosis as a model of lung disease. As a proof of concept, we dissected the evidence that several treatments used to treat RA and ILD such as glucocorticoids, pirfenidone, disease modifying antirheumatic drugs, targeted biologics such as tumor necrosis factor (TNF)-inhibitors, rituximab, tocilizumab, and nintedanib may act indirectly on the CS, suggesting that the CS might represent a potential therapeutic target in these complex diseases.

Diagnostic Performance of Biomarkers for Bladder Cancer Detection Suitable for Community and Primary Care Settings: A Systematic Review and Meta-Analysis.

Evidence on the use of biomarkers to detect bladder cancer in the general population is scarce. This study aimed to systematically review evidence on the diagnostic performance of biomarkers which might be suitable for use in community and primary care settings [PROSPERO Registration: CRD42021258754]. Database searches on MEDLINE and EMBASE from January 2000 to May 2022 resulted in 4914 unique citations, 44 of which met inclusion criteria. Included studies reported on 112 biomarkers and combinations. Heterogeneity of designs, populations and outcomes allowed for the meta-analysis of three biomarkers identified in at least five studies (NMP-22, UroVysion, uCyt+). These three biomarkers showed similar discriminative ability (adjusted AUC estimates ranging from 0.650 to 0.707), although for NMP-22 and UroVysion there was significant unexplained heterogeneity between included studies. Narrative synthesis revealed the potential of these biomarkers for use in the general population based on their reported clinical utility, including effects on clinicians, patients, and the healthcare system. Finally, we identified some promising novel biomarkers and biomarker combinations (N < 3 studies for each biomarker/combination) with negative predictive values of ≥90%. These biomarkers have potential for use as a triage tool in community and primary care settings for reducing unnecessary specialist referrals. Despite promising emerging evidence, further validation studies in the general population are required at different stages within the diagnostic pathway.

Factors influencing symptom appraisal and help-seeking of older adults with possible cancer: a mixed-methods systematic review.

BACKGROUND: The cancer burden falls predominantly on older (≥65 years) adults. Prompt presentation to primary care with cancer symptoms could result in earlier diagnosis. However, patient symptom appraisal and help-seeking decisions involving cancer symptoms are complex and may be further complicated in older adults. AIM: To explore the effect of older age on patients' appraisal of possible cancer symptoms and their decision to seek help for these symptoms. DESIGN AND SETTING: Mixed-methods systematic review. METHOD: MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane Library, Web of Science Core Collection, ASSIA, the ISRCTN registry, and the National Institute for Health and Care Excellence were searched for studies on symptom appraisal and help-seeking decisions for cancer symptoms by adults aged ≥65 years. Studies were analysed using thematic synthesis and according to the Synthesis Without Meta-Analysis guidelines. RESULTS: Eighty studies were included with a total of 32 995 participants. Studies suggested a possible association between increasing age and prolonged symptom appraisal interval. Reduced knowledge of cancer symptoms and differences in symptom interpretation may contribute to this prolonged interval. In contrast, in the current study a possible association was found between increasing age and prompt help-seeking. Themes affecting help-seeking in older adults included the influence of family and carers, competing priorities, fear, embarrassment, fatalism, comorbidities, a desire to avoid doctors, a perceived need to not waste doctors' time, and patient self-management of symptoms. CONCLUSION: This review suggests that increasing age is associated with delayed cancer symptom appraisal. When symptoms are recognised as potentially serious, increasing age was associated with prompt help-seeking although other factors could prolong this. Policymakers, charities, and GPs should aim to ensure older adults are able to recognise potential symptoms of cancer and seek help promptly.

Factors affecting the decision to investigate older adults with potential cancer symptoms: a systematic review.

BACKGROUND: Older age and frailty increase the risk of morbidity and mortality from cancer surgery and intolerance of chemotherapy and radiotherapy. The effect of old age on diagnostic intervals is unknown; however, older adults need a balanced approach to the diagnosis and management of cancer symptoms, considering the benefits of early diagnosis, patient preferences, and the likely prognosis of a cancer. AIM: To examine the association between older age and diagnostic processes for cancer, and the specific factors that affect diagnosis. DESIGN AND SETTING: A systematic literature review. METHOD: Electronic databases were searched for studies of patients aged >65 years presenting with cancer symptoms to primary care considering diagnostic decisions. Studies were analysed using thematic synthesis and according to the Synthesis Without Meta-analysis guidelines. RESULTS: Data from 54 studies with 230 729 participants were included. The majority of studies suggested an association between increasing age and prolonged diagnostic interval or deferral of a decision to investigate cancer symptoms. Thematic synthesis highlighted three important factors that resulted in uncertainty in decisions involving older adults: presence of frailty, comorbidities, and cognitive impairment. Data suggested patients wished to be involved in decision making, but the presence of cognitive impairment and the need for additional time within a consultation were significant barriers. CONCLUSION: This systematic review has highlighted uncertainty in the management of older adults with cancer symptoms. Patients and their family wished to be involved in these decisions. Given the uncertainty regarding optimum management of this group of patients, a shared decision-making approach is important.

FGFR3 mutation affects cell growth, apoptosis and attachment in keratinocytes.

FGFR3 mutations have recently been identified in several benign epidermal skin lesions such as seborrheic keratosis, epidermal nevus and solar lentigo. The functional consequences of these mutations in human skin are as yet unknown. In this study we analyzed the functional effects of the most common FGFR3 mutation in benign skin tumors, the R248C FGFR3 hotspot mutation, in human HaCaT keratinocytes. The cells were stably transduced with either the R248C or wildtype FGFR3 IIIb cDNA using a retroviral vector system. FGFR3 mutant and wildtype cells showed similar growth rates at subconfluence. However, at confluence FGFR3 mutant keratinocytes revealed a significantly higher cell number than wildtype cells. Furthermore, FGFR3 mutant cells showed significantly lower levels of apoptosis and decreased attachment to fibronectin compared with FGFR3 wildtype cells. Expression of mutant FGFR3 did not alter migration and senescence. Microarray analysis revealed only a few differentially expressed genes between FGFR3 mutant and wildtype keratinocytes. Enhanced phosphorylation of ERK1/2 was observed in confluent R248C mutant HaCaT cells compared with wildtype keratinocytes. Our results suggest that an increased cell number at confluence along with a decreased apoptosis may contribute to the development of acanthotic tumors in FGFR3 mutant skin in vivo.

Human Leukocyte Antigen (HLA) Typing Study Identifies Maternal DQ2 Susceptibility Alleles among Infertile Women: Potential Associations with Autoimmunity and Micronutrients.

BACKGROUND: The interplay between female fertility and autoimmune diseases (AIDs) can involve HLA haplotypes and micronutrients. We analyzed the distribution of HLA-DQ2/-DQ8 in women with infertility or recurrent spontaneous abortion (RSA) and possible associations with AIDs and micronutrient status. METHODS: Consecutive women (n = 187) with infertility and RSA, and controls (n = 350) were included. All women were genotyped for HLA-DQ2 (DQA1*0201, A1*05, and B1*02) and -DQ8 (DQA1*03 and DQB1*0302) alleles. Serum 25(OH)D, VB12, folate, and ferritin were evaluated. RESULTS: DQA1*05/B1*02 and the occurrence of at least one DQ2 allele were more prevalent among RSA and infertile women than controls. Infertile women showed lower 25(OH)D and higher prevalence of AIDs than RSA women. In the multivariate analysis, DQA1*05/B1*02 was associated with a significantly higher risk of AIDs in infertile women, and DQA1*05 was independently associated with both 25(OH)D deficiency and AIDs. In RSA women, the presence of AIDs was associated with a significantly higher risk of 25(OH)D deficiency. CONCLUSION: Our findings showed, for the first time, a higher proportion of DQ2 alleles in infertile and RSA women as compared to controls. Predisposing DQ2 alleles are independent risk factors for AIDs and 25(OH)D deficiency in infertile women and could represent biomarkers for performing early detection of women requiring individually tailored management.

Tackling the autoimmune side in Spondyloarthritis: A systematic review.

Spondyloarthritis (SpA) are a heterogeneous group of inflammatory chronic diseases characterized by sharing common pathogenic, clinical and radiologic features. The aim of this review is to support clinicians in understanding and managing this complex disease, from pathogenesis to therapeutic targets, through a systematic review of the current literature in accordance with PRISMA guidelines and checklist. HLA-B27 has been found to be associated with axial involvement either in SA and in PsA patients: it might be involved through presentation of an "arthritogenic peptide" to autoreactive CD8+ T cells or might accumulate in misfolded form and induce production pro-inflammatory cytokines by binding to several innate immune receptors. This genetic background in combination with mechanical stress leads to the activation of both innate and acquired immune responses as well as a possible role of autoimmunity in SpA pathogenesis. The release of IL-23 and IL-17 is relevant for their systemic and local effect on bone, inducing the activation of osteoclasts. Thus, the regulatory role of IL-17 on fibroblasts, osteoblasts and chondrocytes has an impact in both synovial inflammation and joint destruction. Innovative therapies targeting IL-12/23 and IL-17 and the use of small targeted synthetic molecules, as JAK-inhibitors, proved to be effective in SpA patients representing an alternative strategy to TNF-inhibitors.

Retention rates and identification of factors associated with anti-TNFα, anti-IL17, and anti-IL12/23R agents discontinuation in psoriatic arthritis patients: results from a real-world clinical setting.

INTRODUCTION: Biologic disease-modifying antirheumatic drugs (bDMARDs) play a pivotal role in the treatment of psoriatic arthritis (PsA). Despite this, their discontinuation due to inefficacy or adverse events is often observed. The aims of this study are to describe retention rates and treatment trends of anti-TNFα, anti-IL17, and anti-IL12/23R agents in patients with PsA and to identify factors associated with bDMARDs discontinuation in a real-world clinical setting. METHODS: A retrospective cohort study based on the analysis of the three Italian prescription cohorts of patients with PsA has been performed. Survival analysis was performed using Kaplan-Meier curves and Cox proportional-hazards model. RESULTS: During the follow up, which lasted 25.5 (12-60) months, 68 patients discontinued a bDMARD: 13 for primary failure, 12 for secondary failure, 15 for adverse events, 5 for remission, 12 because of lost at follow-up, and 11 for other causes. Cox proportional-hazards demonstrated that a shorter disease duration (HR 0.994991, 95% CI 0.9910336-0.9989647, p = 0.014) and first-line bDMARD (HR 0.5090986, 95% CI 0.3073519-0.8432722, p = 0.009) have a protective role on bDMARD retention rate, while the multivariable analysis failed in demonstrating an independent protective role of male sex on drug retention rate (p = 0.083). No significant differences in retention rate have been found regarding biologic drugs, combination therapy or monotherapy, and class of bDMARD (anti-TNFα or anti-pIL12/23R and anti-IL-17). CONCLUSIONS: This study shows that a shorter disease duration and treatment with a first-line bDMARD are predictors of bDMARDs retention rate, further highlighting the importance of early diagnosis of PsA. Key Points • No significant difference in retention among patients treated with anti-IL17A, anti-IL12/23R, and anti-TNFα agents has been demonstrated. • A shorter disease duration and first-line bDMARD treatment are associated with persistence in biologic treatment.

Assessing an intervention to increase knowledge related to cervical cancer and the HPV vaccine.

Human papillomavirus (HPV) infection is the primary risk factor for cervical cancer. While the HPV vaccine significantly reduces the risk of HPV infection and subsequent cervical cancer diagnosis, underuse is linked to lack of knowledge of its effectiveness in preventing cervical cancer. The purpose of this study was to evaluate a cancer educational intervention (titled "MOVENUP") to improve knowledge of cervical cancer, HPV, and the HPV vaccine among predominantly African American communities in South Carolina. The MOVENUP cancer educational intervention was conducted among participants residing in nine South Carolina counties who were recruited by community partners. The 4.5-h MOVENUP cancer educational intervention included a 30-min module on cervical cancer, HPV, and HPV vaccination. A six-item investigator-developed instrument was used to evaluate pre- and post-intervention changes in knowledge related to these content areas. Ninety-three percent of the 276 participants were African American. Most participants reporting age and gender were 50+ years (73%) and female (91%). Nearly half of participants (46%) reported an annual household income <$40,000 and 49% had not graduated from college. Statistically significant changes were observed at post-test for four of six items on the knowledge scale (P<0.05), as compared to pre-test scores. For the two items on the scale in which statistically significant changes were not observed, this was due primarily due to a baseline ceiling effect.

One-year effectiveness, retention rate, and safety of secukinumab in ankylosing spondylitis and psoriatic arthritis: a real-life multicenter study.

BACKGROUND: Secukinumab (SEC) is effective for ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in randomized trials, but real-life data are lacking. RESEARCH DESIGN AND METHODS: Real-life, prospective observational study on 169 consecutive outpatients at baseline (T0) and at 6 (T6) and 12 months (T12) after starting SEC (39 AS, 23%; 130 PsA, 77%). RESULTS: Significant improvement was seen at T6 and T12 for all clinical variables, including TJC, SJC, ESR, CRP, DAPSA, ASDAS-CRP, and BASDAI, as well as in patient-reported outcomes like VAS-pain. By multivariable regression analysis, in AS patients high BASDAI at T0 correlated with diagnostic delay (R2 = 0.4; p = 0.009) and peripheral joint involvement (R2 = 0.4; p = 0.04). During follow-up, reduction of BASDAI positively correlated with high ESR (R2 = 0.65; p = 0.04). ASDAS-CRP at T0 positively correlated with high ESR (R2 = 0.34; p = 0.004). Reduction of ASDAS-CRP from T0 to T6 correlated with current smoking status (R2 = 0.42; p = 0.003). In PsA patients, reduction of DAPSA score from T0 to T12 is negatively correlated with the presence of metabolic syndrome (R2 = 0.41; p = 0.0025). SEC was well tolerated; 10 patients discontinued treatment for non-severe adverse events. CONCLUSIONS: Secukinumab is effective and safe in patients with AS and PsA in a real-life setting.

ETV5 links the FGFR3 and Hippo signalling pathways in bladder cancer.

Activating mutations of fibroblast growth factor receptor 3 (FGFR3) are common in urothelial carcinoma of the bladder (UC). Silencing or inhibition of mutant FGFR3 in bladder cancer cell lines is associated with decreased malignant potential, confirming its important driver role in UC. However, understanding of how FGFR3 activation drives urothelial malignant transformation remains limited. We have previously shown that mutant FGFR3 alters the cell-cell and cell-matrix adhesion properties of urothelial cells, resulting in loss of contact-inhibition of proliferation. In this study, we investigate a transcription factor of the ETS-family, ETV5, as a putative effector of FGFR3 signalling in bladder cancer. We show that FGFR3 signalling induces a MAPK/ERK-mediated increase in ETV5 levels, and that this results in increased level of TAZ, a co-transcriptional regulator downstream of the Hippo signalling pathway involved in cell-contact inhibition. We also demonstrate that ETV5 is a key downstream mediator of the oncogenic effects of mutant FGFR3, as its knockdown in FGFR3-mutant bladder cancer cell lines is associated with reduced proliferation and anchorage-independent growth. Overall this study advances our understanding of the molecular alterations occurring during urothelial malignant transformation and indicates TAZ as a possible therapeutic target in FGFR3-dependent bladder tumours.