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The history of colchicine dates to ancient Egyptians when it was used for alleviation of swelling and pain. Although its popularity varied throughout the years, colchicine has been a mainstay for the treatment of several diseases, mainly rheumatic and cardiac ones. The mechanism of action of the drug involves several intracellular and extracellular targets, although interaction with tubulin is the most described. Based on several clinical trials and meta-analyses, colchicine is safely recommended as a monotherapy or as an add-on for the treatment and prevention of recurrent pericarditis, post-pericardiotomy syndrome, gout, pseudogout, familial Mediterranean fever (FMF), and Behçet’s disease (BD). Notably, drug safety has been noted during pregnancy and lactation. Besides its major indications, colchicine has shown efficacy and safety in the treatment of various conditions. Because the indications for using colchicine in the prevention of certain conditions such as acute coronary syndrome, stroke, and hepatic cirrhosis and treatment of others such as pneumonia and psoriasis are still debatable, further research works are needed.

A 53-year-old man presented with a painful swollen right calf. The day before, he was walking uphill on a cold afternoon after finishing work. Suddenly, he stepped on a shallow hole in the pavement, his foot went up and his knee straightened backwards. At the same time, he felt someone had kicked

Salem and Zahran[1][1] conducted a cross sectional study investigating the role of VCAM-1 in patients with rheumatoid arthritis (RA), its relation to disease activity, oxidative stress and systemic inflammation.[1][1] They studied 50 patients with early newly diagnosed RA (less than 6 month duration

Objectives About half of RA patients treated with TNFα inhibitors either do not respond or lose their initial therapeutic response over time. The clinical response is measured by reduction in DAS28, which primarily reflects inflammation. However, other effects of TNFα inhibitors, such as impact on bone erosion, are not assessed by DAS28. We aimed to examine the effect of TNFα inhibitors on bone density, bone biomarkers and cytokine production in responder and non-responder patients and assessed mechanisms of action. Methods BMD in the lumbar spine and femur neck of 117 RA patients was measured by DEXA scan. Bone turnover biomarkers CTX, osteoprotegerin (OPG), osteocalcin and RANKL were measured by ELISA. Levels of 16 cytokines in plasma and in tissue culture supernatants of ex vivo T cells were measured by multiplex assays and ELISA. The effect of treatment with TNFα inhibitors on blood mononuclear cell (MNC) differentiation to osteoclast precursors (OCP) was measured flow cytometry and microscopy. Results TNFα inhibitors improved lumbar spine BMD but had modest effects on blood bone biomarkers, irrespective of patients’ clinical response. Blood OCP numbers and the ability of monocytes to differentiate to OCP in vitro declined after treatment. Treatment also reduced RANK expression and IL-20 production. BMD improvement correlated with reduced levels of IL-20 in responder patients. Conclusion This study reveals that TNFα inhibitors reduce lumbar spine bone loss in RA patients irrespective of changes in DAS28. The reduction in bone loss is associated with reduction in IL-20 levels in responder patients.

Calcinosis cutis is a deposition of calcium salts in the skin and subcutaneous tissue which can occur in connective tissue diseases such as scleroderma, dermatomyositis, myositis and overlap syndrome, but rarely in association with systemic lupus erythematosus (SLE). It is subdivided into a localized ‘circumscripta’ and diffuse ‘universalis’. The few reported cases of calcinosis in SLE were mainly of the circumscripta type. Calcinosis universalis is extremely rare and is usually associated with a history of chronic active SLE in female patients, with few proven effective treatments. We report a case of a young female patient with a long and complicated history of SLE. She presented with widespread pain and tenderness associated with multiple subcutaneous skin lesions. She was found to have evidence of calcinosis universalis on X-rays. Investigations did not reveal any associated conditions that could explain this diagnosis other than her prolonged history of SLE.

Since the 2019 novel coronavirus (COVID-19) was first detected in December 2019, research on the complications and fatality of this virus has hastened. Initially, case reports drew an association between COVID-19 and abnormal coagulation parameters. Subsequently, cross-sectional studies found a high prevalence of thrombosis among ICU and non-ICU COVID-19 patients. For that reason, certain studies tried to explain the pathogenic mechanisms of thrombosis, one of which was the emergence of anti-phospholipid antibodies (aPL). Although aPL have been found positive in very few patients, their association with thrombotic events stays debatable. Given the thrombotic manifestations of COVID-19 and the potential role of aPL, the catastrophic form of APS (CAPS) might be a major fatal phenomenon. However, to date, there has been no clear association of CAPS to COVID-19. Moreover, since infections, including viral respiratory similar to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are considered main etiologies for CAPS, it could be possible that SARS-CoV-2 can induce CAPS although no evidence is currently found. High quality studies are needed to develop a clear idea on the pathogenic role of aPL in the progression of thrombosis in COVID-19 patients, and how such patients could be fit into a thromboprophylaxis plan.

Whether affecting children or adults, SARS-CoV-2 infection (COVID-19) can have multi-organ involvement mediated by an inflammatory cascade. Immunoglobulin A (IgA) is one of the key components of the inflammatory cascade that can lead to endothelial injury and inflammation. IgA vasculitis or Henoch-Schönlein purpura (HSP) has been rarely reported in the context of COVID-19. In this report, we highlight a case of HSP occurring 2 days after diagnosis of COVID-19 in a 16-year-old boy, who presented with palpable purpura of the lower extremities and buttocks, diffuse abdominal pain, hemoptysis, and hematochezia. He was treated with oral prednisolone with rapid clinical improvement.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can show musculoskeletal symptoms such as peripheral arthritis. In rare cases, peripheral arthritis can develop after the resolution of SARS-CoV-2. We present two cases of spondyloarthritis induced by SARS-CoV-2; one case with axial and peripheral spondyloarthritis and the other with peripheral spondyloarthritis. Both cases refer to Lebanese patients who were HLA-B27 positive. These two cases highlight the possible predisposition of HLA-B27 positive patients to the development of spondyloarthritis symptoms triggered by SARS-CoV-2.

With increasing longevity of the population globally, the prevalence of osteoporosis will rise, associated with significant morbidity, disability and increased mortality. Adequate intake of calcium, vitamin D, increasing physical activity, a strategy of avoiding falls, cessation of smoking and avoiding excessive alcohol intake are pivotal in maintaining healthy bones in all age groups. Oral bisphosphonates remain the most cost-effective first line of treatment. Better methods of identifying patients with high fracture risk is needed as there is adequate effective treatment for osteoporosis.

A project aimed to develop and deliver a clinical training course in Accra, Ghana, to increase patient access to physicians trained in the diagnosis, treatment and management of rheumatological conditions. We started with a scoping exercise followed by collaborative course curriculum development, co-delivered training course facilitated by both locally based rheumatologists and international faculty members. Evaluation data gathered from application forms, participant feedback forms and multiple-choice tests completed at the beginning and end of training and the test scores compared to evaluate a change in knowledge. A 4-day clinical training course developed and delivered to twenty medical professionals based across Ghana. Test scores suggest a 15.83% increase in clinical knowledge. The training model with the curriculum design and delivery teams drawing expertise from both locally based rheumatologists and internationally based faculty has guaranteed both world-class approach and content while ensuring contextual relevance. The inclusion of leadership and Training of Trainer (ToT) elements into the model of training has maximised reach and increased teaching capacity. The programme has been well-received by participating medical professionals and faculty and has been demonstrated to be effective within this multinational programme and the methodology may be applicable to similar needs in other countries.

Background Familial Mediterranean Fever (FMF) is one of the most common hereditary auto-inflammatory diseases especially among Arabs, Armenians, Jews, and Turks characterized by recurrent attacks of fever, abdominal pain and arthritis.Whether the prevalence of ankylosing spondylitis (AS) is increased in FMF patients is a matter of debate. This review will summarize all the literature data relevant to this topic. Methods We searched all the articles through PubMed and Embase databases from 1963 until 2017 addressing the relationship between AS and FMF patients. Results The prevalence of AS among FMF patients is highly variable. However, a significant relationship was found to exist between MEFV gene mutations and AS. Most patients with coexistent MEFV gene mutations and AS were human leucocyte antigen B27 (HLA-B27) negative. The effect of these mutations on AS severity and prognosis was not significant. Conclusion Large based population studies are needed to further assess the existence of MEFV gene mutations among AS patients and their effect on the clinical course of the disease in addition to assessment of AS prevalence in patients with FMF.

TNFα is a principal pro-inflammatory cytokine vital for immunity to infections. However, its excessive production is involved in chronic inflammation and disease pathology in autoimmune diseases. Evidence for its pathogenic role is validated by the fact that its neutralisation by therapeutic agents in vivo is beneficial in ameliorating disease and controlling symptoms. Paradoxically, however, treatment with TNFα inhibitors can either have no clinical effects, or even exacerbate disease in some patients. The explanation for such contradictory outcomes may lay in how and which downstream signalling pathways are activated and drive disease. TNFα causes its effects by binding to either or both of two membrane-bound receptors, TNFR1 and TNFR2. Engagement of the receptors can induce cell death or cell proliferation. T cells both produce and respond to TNFα and depending on whether the cytokine is membrane-bound or soluble and the level of expression of its two receptors, the biological outcome can be distinct. In addition, polymorphisms in genes encoding TNFα and T cell signalling proteins can significantly impact the outcome of TNFα receptor engagement. Early studies revealed that effector T cells in patients with rheumatoid arthritis (RA) are hyporesponsive due to chronic exposure to TNFα. However, recent evidence indicates that the relationship between TNFα and T cell responses is complex and, at times, can be paradoxical. In addition, there is controversy as to the specific effects of TNFα on different T cell subsets. This review will summarise knowledge on how TNFα modulates T cell responses and the effect of engaging either of its two receptors. Furthermore, we discuss how such interactions can dictate the outcome of treatment with TNFα inhibitors.

Alghanim and Gasmelseed postulate that dermatomyositis (DM) in the patient who later developed Kaposi’s sarcoma (KS) was a paraneoplastic syndrome.[1][1] We do not agree with their hypothesis. Paraneoplastic syndromes are rare disorders that develop when T lymphocytes directed against antigens

[No Abstract Available] Saudi Med J 2020; Vol. 41 (4): 436-437 doi: 10.15537/smj.2020.4.25013 Howo to cite this article: Jawad AS. Comment on: Variables associated subclinical atherosclerosis among rheumatoid arthritis patients of Gulf Cooperative Council countries. Saudi Med J 2020; Vol. 41 (4): 436-437. doi: 10.15537/smj.2020.4.25013

Informed consent: No informed consent was obtained from the patient because we lost complete contact with him. Additionally, we made sure that no personal information has been revealed in the manuscript.

[No Abstract Available ] Saudi Med J 2018; Vol. 39 (2): 121-123 doi: 10.15537/smj.2018.2.22197 How to cite this article: Jawad AS. The Royal College of Physicians of London 500th Anniversary. Saudi Med J . 2018 Feb;39(2):121-123. doi: 10.15537/smj.2018.2.22197.

BackgroundFamilial Mediterranean Fever (FMF), an autoinflammatory disease, is characterized by self-limited inflammatory attacks of fever and polyserositis along with high acute phase response. Although colchicine remains the mainstay in treatment, intolerance and resistance in a certain portion of patients have been posing a problem for physicians.Main bodyLike many autoimmune and autoinflammatory diseases, many colchicine-resistant or intolerant FMF cases have been successfully treated with biologics. In addition, many studies have tested the efficacy of biologics in treating FMF manifestations.ConclusionSince carriers of FMF show significantly elevated levels of serum TNF alpha, IL-1, and IL-6, FMF patients who failed colchicine were successfully treated with anti IL-1, anti IL-6, or TNF inhibitors drugs. It is best to use colchicine in combination with biologics.

Editor – We are surprised at the lack of mention of the Medical Training Initiative (MTI) scheme which is run by a number of ­medical royal colleges in the article by Jalal et al .1 Currently there are over 300 physicians working and training in the UK on the Royal College of Physicians (RCP) scheme for up to 2 years. The RCP provides support to these trainees once in the UK, …

[No Available Abstract] Saudi Med J. 2020 Dec;41(12):1381 doi: 10.15537/smj.2020.12.25571 How to cite this article: Jawad AS. Comment on: The current practice of using angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in diabetic hypertensive and non-hypertensive patients. Is there a room for vitamin D? Saudi Med J. 2020 Dec;41(12):1381. doi: 10.15537/smj.2020.12.25571. PMID: 33294899.

To the Editor The article by Alraddadi et al is timely and welcome.[1][1] Effective patient physician communication is fundamental to successful clinical practice.[2][2] Establishing rapport between physician and patient is paramount. This is achieved by attentive listening, showing empathy

In this article, we report a case of pneumatosis intestinalis associated with tocilizumab use. This is a unique case and may explain the increased rate of idiopathic bowel perforation among patients taking tocilizumab.

Objectives: There is limited data examining the reliability and consistency of objective measures of osteoarthritis (OA) function. Therefore the aim of this study was to assess their test/retest reliability. Methods: 21 postmenopausal women over the age of 50 diagnosed with bilateral knee OA were recruited from a single centre. Endpoints assessed included time to walk 20 m, 40 m, ascend and descend 11 stairs, pain scores, standard WOMAC questionnaires and range of motion of the knee with assessments repeated at a follow up visit. Results: Time to walk 20 m, 40 m, and climb and descend stairs and total WOMAC scores between the two visits was highly reliable. There was no reliability for the range of motion of the knee. Conclusions: The high degree of reliability for the endpoints of walking and stair climbing within patients and across visits supports the use of these as outcome measures within clinical trials of OA.

Introduction : in-service training of healthcare workers is essential for improving healthcare services and outcome. Methods : The Millennium Development Goal (MDG) 6 Partnership for African Clinical Training (M-PACT) program was an innovative in-service training approach designed and implemented by the Royal College of Physicians (RCP) and West African College of Physicians (WACP) with funding from Eco Bank Foundation. The goal was to develop sustainable capacity to tackle MDG 6 targets in West Africa through better postgraduate medical education. Five training centres were establised: Nigeria (Abuja, Ibadan), Ghana (Accra), Senegal (Dakar) and Sierra Leone (Freetown) for training 681 physicians from across West Africa. A curriculum jointly designed by the RCP-WACP team was used to deliver biannual 5-day training courses over a 3-year period. Results : Of 602 trained in clinical medicine, 358 (59.5%) were males and 535 (88.9%) were from hosting countries. 472 (78.4%) of participants received travel bursaries to participate, while 318 (52.8%) were residents in Internal Medicine in the respective institutions. Accra had the highest number of participants (29.7%) followed by Ibadan, (28.7%), Dakar, (24.9%), Abuja, (11.0%) and Freetown, (5.6%). Pre-course clinical knowledge scores ranged from 35.1% in the Freetown Course to 63.8% in Accra Course 1; whereas post-course scores ranged from 50.5% in the Freetown course to 73.8% in Accra course 1. Conclusion : M-PACT made a positive impact to quality and outcome of healthcare services in the region and is a model for continued improvement for healthcare outcomes, e.g malaria, HIV and TB incidence and mortality in West Africa

[No Abstract Available] Saudi Med J 2019; Vol. 40 (2): 202-203 doi: 10.15537/smj.2019.2.23945 How to cite this article: Jawad A. Subclinical coronary artery disease in recent-onset of rheumatoid arthritis. Saudi Med J . 2019 Feb;40(2):202. doi: 10.15537/smj.2019.2.23945.

Objectives: To evaluate the efficacy of orally-administered alendronate compared with intravenously-administered zoledronate. Methods: This prospective study was carried out at Barts Health HNS Trust between April 2010 and March 2012. This study compares changes in bone mineral density (BMD) in 234 patients treated with 2 bisphosphonates: alendronate taken orally, and zoledronate administered intravenously. One hundred and eighteen patients received alendronate at 70 mg/week, while 116 patients received zoledronate once annually. Dual energy x-ray absorptiometry was used to measure BMD of the left hip and anterior-posterior spine (lumbar L1-L4) skeletal sites at baseline, and at one-, and 2-years post-treatment. Results: This study provides evidence that lumbar spine BMD increased by 3.6% in patients receiving alendronate, and 5.7% in patients receiving zoledronate after 2 years compared with baseline values ( p =0.0001 for both). Total hip BMD decreased in patients treated with alendronate by 0.4% but increased in patients receiving zoledronate by 0.8% ( p =0.0001). Conclusion: This study provides evidence that zoledronate is more effective than alendronate in treating patients with osteoporosis and with no gastrointestinal (GI) serious side effects. Furthermore, zoledronate appears to have the added advantage of a better safety profile in patients suffering from GI intolerance of oral bisphosphonates. Saudi Med J 2015; Vol. 36 (11): 1305-1311 doi: 10.15537/smj.2015.11.12731

Familial Mediterranean fever is an autoinflammatory multisystem disease, which most commonly affects patients from the Mediterranean basin. This review discusses the common polymorphisms in the MEFV gene as well as the role of pyrin in disease pathogenesis. Patients with familial Mediterranean fever typically develop peritonitis, pleuritis, arthritis, and fever. In addition, a number of authors have reported ophthalmic features. These case reports and series are further explored in this review. Colchicine has transformed the prognosis for patients with familial Mediterranean fever. The rationale for the use of colchicine, as well as the evidence for newer biologic agents is also covered.

Background Granulomatosis with polyangiitis (GPA, formerly Wegener’s granulomatosis) is a multisystem vasculitis of small- to medium-sized blood vessels. Cranial involvement can result in cranial nerve palsies and, rarely, pituitary infiltration. Case presentation We describe the case of a 32 year-old woman with limited but severe GPA manifesting as progressive cranial nerve palsies and pituitary dysfunction. Our patient initially presented with localised ENT involvement, but despite treatment with methotrexate, she deteriorated. Granulomatous inflammatory tissue around the skull base resulted in cavernous sinus syndrome, facial nerve palsy, palsies of cranial nerves IX-XII (Collet-Sicard syndrome), and the rare complication of cranial diabetes insipidus due to pituitary infiltration. The glossopharyngeal, vagus and accessory nerve palsies resulted in severe dysphagia and she required nasogastric tube feeding. Her neurological deficits substantially improved with treatment including high dose corticosteroid, cyclophosphamide and rituximab. Conclusions This case emphasises that serious morbidity can arise from localised cranial Wegener’s granulomatosis in the absence of systemic disease. In such cases intensive induction immunosuppression is required. Analysis of previously reported cases of pituitary involvement in GPA reveals that this rare complication predominantly affects female patients.

Biologic TNFα inhibitors are a mainstay treatment option for patients with rheumatoid arthritis (RA) refractory to other treatment options. However, many patients either do not respond or relapse after initially responding to these agents. This study was carried out to identify biomarkers that can distinguish responder from non-responder patients before the initiation of treatment. The level of cytokines in plasma and those produced by ex vivo T cells, B cells and monocytes in 97 RA patients treated with biologic TNFα inhibitors was measured before treatment and after 1 and 3 months of treatment by multiplex analyses. The frequency of T cell subsets and intracellular cytokines were determined by flow cytometry. The results reveal that pre-treatment, T cells from patients who went on to respond to treatment with biologic anti-TNFα agents produced significantly more GM-CSF than non-responder patients. Furthermore, immune cells from responder patients produced higher levels of IL-1β, TNFα and IL-6. Cytokine profiling in the blood of patients confirmed the association between high levels of GM-CSF and responsiveness to biologic anti-TNFα agents. Thus, high blood levels of GM-CSF pre-treatment had a positive predictive value of 87.5% (61.6 to 98.5% at 95% CI) in treated RA patients. The study also shows that cells from most anti-TNFα responder patients in the current cohort produced higher levels of GM-CSF and TNFα pre-treatment than non-responder patients. Findings from the current study and our previous observations that non-responsiveness to anti-TNFα is associated with high IL-17 levels suggest that the disease in responder and non-responder RA patients is likely to be driven/sustained by different inflammatory pathways. The use of biomarker signatures of distinct pro-inflammatory pathways could lead to evidence-based prescription of the most appropriate biological therapies for different RA patients.

Human γδ T cells display potent responses to pathogens and malignancies. Of particular interest are those expressing a γδ T-cell receptor (TCR) incorporating TCRδ-chain variable-region-2 [Vδ2(+)], which are activated by pathogen-derived phosphoantigens (pAgs), or host-derived pAgs that accumulate in transformed cells or in cells exposed to aminobisphosphonates. Once activated, Vδ2(+) T cells exhibit multiple effector functions that have made them attractive candidates for immunotherapy. Despite this, clinical trials have reported mixed patient responses, highlighting a need for better understanding of Vδ2(+) T-cell biology. Here, we reveal previously unappreciated functional heterogeneity between the Vδ2(+) T-cell compartments of 63 healthy individuals. In this cohort, we identify distinct "Vδ2 profiles" that are stable over time; that do not correlate with age, gender, or history of phosphoantigen activation; and that develop after leaving the thymus. Multiple analyses suggest these Vδ2 profiles consist of variable proportions of two dominant but contrasting Vδ2(+) T-cell subsets that have divergent transcriptional programs and that display mechanistically distinct cytotoxic potentials. Importantly, an individual's Vδ2 profile predicts defined effector capacities, demonstrated by contrasting mechanisms and efficiencies of killing of a range of tumor cell lines. In short, these data support patient stratification to identify individuals with Vδ2 profiles that have effector mechanisms compatible with tumor killing and suggest that tailored Vδ2-profile-specific activation protocols may maximize the chances of future treatment success.

[No Abstract Available] Saudi Med J 2018; Vol. 39 (5): 526-527 doi: 10.15537/smj.2018.5.22199 How to cite this article: Fairweather J, Jawad AS. Post-traumatic chronic seronegative monarthritis responding to antitumor necrosis factor-alpha therapy. Saudi Med J . 2018 May;39(5):526-527. doi: 10.15537/smj.2018.5.22199.

Relapsing polychondritis is a rare immune-mediated condition, causing inflammation of cartilage and other structures, and associated with a high mortality. Its heterogenic nature and rarity raises a number of diagnostic and treatment challenges.

Infection by respiratory syncytial virus (RSV) affects approximately 33 million infants annually worldwide and is a major cause of hospitalizations. Helper T lymphocytes (Th) play a central role in the immune response during such infections. However, Th lymphocytes that produce interleukin 17 (IL-17), known as Th17 lymphocytes, in addition to been protective can also cause pathology that accompany this type of infection. The protective effects of Th17 is associated with better prognosis in most infected individuals but heightened Th17 responses causes inflammation and pathology in others. Studies employing animal models haves shown that activated Th17 lymphocytes recruit neutrophils and facilitate tertiary lymphoid structure development in infected lungs. However, IL-17 also inhibits the ability of CD8+ lymphocytes to clear viral particles and acts synergistically with the innate immune system to exacerbate inflammation. Furthermore, IL-17 enhances IL-13 production which, in turn, promotes the activation of Th2 lymphocytes and excessive mucus production. Studies of these animal models have also shown that a lack of, or inadequate, responses by the Th1 subset of T lymphocytes enhances Th17-mediated responses and that this is detrimental during RSV co-infection in experimental asthma. The available evidence, therefore, indicates that Th17 can play contradictory roles during RSV infections. The factors that determine the shift in the balance between beneficial and adverse Th17 mediated effects during RSV infection remains to be determined.

Objectives To establish if changes in Th1/Th17 cell populations previously reported in experimental arthritis occur in patients with rheumatoid arthritis (RA) treated with anti-tumour necrosis factor α (TNFα) agents, and whether the therapeutic response to anti-TNFα is compromised in patients and mice because of elevated Th17/IL-17 levels. Finally, to assess the efficacy of combined blockade of anti-TNFα and anti-IL-17 in experimental arthritis. Methods A longitudinal study of two independent cohorts (cohort 1, n=24; cohort 2, n=19) of patients with RA treated with anti-TNFα biological agents was carried out to assess their Th17/IL-17 levels before and after the start of anti-TNFα therapy. IL-12/23p40 production was assessed in plasma Peripheral blood lymphocytes (PBLs) and monocytes. Mice with collagen-induced arthritis (CIA) were treated with anti-TNFα alone, anti-IL17 alone or a combination of the two. Efficacy of treatment and response was assessed from changes in Disease Activity Score 28–erythrocyte sedimentation rate scores in patients, and in clinical scores and histological analysis in CIA. Results Significant increases in circulating Th17 cells were observed in patients after anti-TNFα therapy and this was accompanied by increased production of IL-12/23p40. There was an inverse relationship between baseline Th17 levels and the subsequent response of patients with RA to anti-TNFα therapy. In addition, PBLs from non-responder patients showed evidence of increased IL-17 production. Similarly, in anti-TNFα-treated mice, there was a strong correlation between IL-17 production and clinical score. Finally combined blockade of TNFα and IL-17 in CIA was more effective than monotherapy, particularly with respect to the duration of the therapeutic effect. Conclusions These findings, which need to be confirmed in a larger cohort, suggest that a Th17-targeted therapeutic approach may be useful for anti-TNFα non-responder patients or as an adjunct to anti-TNFα therapy, provided that safety concerns can be addressed.

In this in-depth review, we examine the worldwide epidemiology of SLE and summarize current knowledge on the influence of race/ethnicity on clinical manifestations, disease activity, damage accumulation and outcome in SLE. Susceptibility to SLE has a strong genetic component, and trans-ancestral genetic studies have revealed a substantial commonality of shared genetic risk variants across different genetic ancestries that predispose to the development of SLE. The highest increased risk of developing SLE is observed in black individuals (incidence 5- to 9-fold increased, prevalence 2- to 3-fold increased), with an increased risk also observed in South Asians, East Asians and other non-white groups, compared with white individuals. Black, East Asian, South Asian and Hispanic individuals with SLE tend to develop more severe disease with a greater number of manifestations and accumulate damage from lupus more rapidly. Increased genetic risk burden in these populations, associated with increased autoantibody reactivity in non-white individuals with SLE, may explain the more severe lupus phenotype. Even after taking into account socio-economic factors, race/ethnicity remains a key determinant of poor outcome, such as end-stage renal failure and mortality, in SLE. Community measures to expedite diagnosis through increased awareness in at-risk racial/ethnic populations and ethnically personalized treatment algorithms may help in future to improve long-term outcomes in SLE.

Background The aim of the study was to compare serum sclerostin levels in human im-munodeficiency virus (HIV)-infected patients and healthy controls, and to evaluate their relationship with bone turnover markers (BTM) and bone mineral density (BMD). Methods We prospectively studied 33 HIV treatment-naive patients and 63 healthy individuals; matched for age and sex. Serum sclerostin levels, BTM, BMD were measured. Viral load and cluster of differentiation 4 (CD4) levels were also assessed in HIV-infected patients. Results The mean±standard deviation (SD) age of sample was 37.6±10.3 years (range, 19 to 59 years). Of the 96 subjects, 58 (60.4%) were male and 38 (39.6%) were female. Infection with HIV is associated with significant reduction in serum sclerostin levels (HIV-infected: 39.4±28.3 vs. non HIV: 76.6±15.7 pmol/L; P0.05). Conclusions These findings suggest that untreated HIV and the resulting immune deficiency and/or systemic inflammation could be an important regulator of serum sclerostin in this population.

Summary Background Recent reports have shown that in the UK there has been a decrease in interest towards pursuing a surgical career, whereas early exposure to surgery may increase interest. We aimed to assess the effect of a 1-day medical school surgical conference in encouraging attendees to pursue a surgical career. Methods All attendees of the 2014 Barts and The London National Undergraduate Surgical conference were invited to participate in an online survey. Data were collected and analysed to evaluate students’ reasons for attending the conference, and attitudes to careers in surgery before and after the conference. Results Of 229 students, 130 (56.8%) completed the survey. Year-12 high-school and preclinical medical students showed a statistically significant difference in interest in pursuing a surgical career after the conference than before it (p = 0.0002 and p = 0.0027, respectively), but clinical medical students demonstrated no such change. Conclusion Attendance at surgical conferences designed for medical students can significantly increase the desire of high-school students and preclinical medical students to pursue a surgical career, but may not have the same effect for clinical medical students. Surgical conferences may act as an effective means of recruiting students towards choosing a surgical career for a certain subset of students.

Inflammatory muscle diseases are a group of muscle disorders characterized by muscle weakness, fatigue, and an association with malignancy and paraneoplastic syndrome. A diagnosis of idiopathic inflammatory myopathy is suggested by abnormal myometry and rising creatine kinase, but tissue diagnosis is also needed. Magnetic resonance imaging (MRI) helps localize the appropriate site of biopsy, demonstrate the extent of muscle involvement, and monitor the response to therapy. However, the sensitivity of magnetic resonance (MR) is limited, and whole-body imaging is still far from routine. [(18) F]Fluoro-desoxy-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) is currently the ultimate metabolic imaging technique for the management of cancer. It has also been shown to detect inflammatory conditions and to monitor their response to treatment. The use of FDG PET in screening for underlying malignancies is widely reported and recommended in patients with paraneoplastic syndrome. Unfortunately, only a few reports have been published to show the value of FDG PET in inflammatory muscle diseases, which as we show herein, deserve further pursuit.