Defining Criteria for Disease Activity States in Systemic Juvenile Idiopathic Arthritis Based on the Systemic Juvenile Arthritis Disease Activity Score.

OBJECTIVE: Our objective was to develop and validate cutoff values in the systemic Juvenile Arthritis Disease Activity Score 10 (sJADAS10) that distinguish the states of inactive disease (ID), minimal disease activity (MDA), moderate disease activity (MoDA), and high disease activity (HDA) in children with systemic juvenile idiopathic arthritis, based on subjective disease state assessment by the treating pediatric rheumatologist. METHODS: The cutoff definition cohort was composed of 400 patients enrolled at 30 pediatric rheumatology centers in 11 countries. Using the subjective physician rating as an external criterion, six methods were applied to identify the cutoffs: mapping, calculation of percentiles of cumulative score distribution, the Youden index, 90% specificity, maximum agreement, and receiver operating characteristic curve analysis. Sixty percent of the patients were assigned to the definition cohort, and 40% were assigned to the validation cohort. Cutoff validation was conducted by assessing discriminative ability. RESULTS: The sJADAS10 cutoffs that separated ID from MDA, MDA from MoDA, and MoDA from HDA were ≤2.9, ≤10, and >20.6, respectively. The cutoffs discriminated strongly among different levels of pain, between patients with and without morning stiffness, and among patients whose parents judged their disease status as remission or persistent activity or flare or were satisfied or not satisfied with current illness outcome. CONCLUSION: The sJADAS cutoffs revealed good metrologic properties in both definition and validation cohorts and are therefore suitable for use in clinical trials and routine practice.

Targeted optimum care approach for osteoporotic fragility fractures: tailored strategy based on risk stratification to reduce incidents of falls-an initiative by the Egyptian Academy of bone health based on the FLS national register.

Since falling is the third cause of chronic disability, a better understanding of the frequency, severity, and risk factors of falls across diagnostic groups is needed to design and implement customized, effective fall prevention, and management programs for these individuals, particularly those at risk of sustaining a fragility fracture. OBJECTIVE: (1) To assess the incidence of falls among osteoporotic patients with fragility fractures. (2) To evaluate the potential for stratifying the people at risk of falling in bone health setting aiming to provide targeted optimum care for them. METHODS: This was a multi-center, cross-sectional, observational study. Both men and postmenopausal women, admitted with an osteoporotic fracture (whether major osteoporosis or hip fracture), were consecutively recruited for this work and managed under Fracture Liaison Service. All the patients were assessed for their Fracture risk (FRAX), falls risk (FRAS), and sarcopenia risk (SARC-F) as well as functional disability (HAQ). Blood tests for bone profile as well as DXA scan were offered to all the patients. RESULTS: Four hundred five patients (121 males, 284 females) were included in this work. Mean age was 70.1 (SD = 9.2) years. The incidence of falls was 64.9%. The prevalence of falls was high (64.8%) in the patients presenting with major osteoporosis fractures and in those with hip fractures (61.8%). The prevalence of fragility fractures was positively correlated with HAQ score and the SARC-F score (p = 0.01 and 0.021 respectively). Falls risk score was positively correlated with FRAX score of major osteoporotic fractures, HAQ score, and SARC-F score (p = 0.01, 0.013, and 0.003 respectively). Seventy percent of the osteopenia patients who sustained fragility fracture had high falls risk and/or SARC-F score. CONCLUSION: This study highlighted the importance of falls risk stratification in osteoporotic patients presenting with fragility fractures. Identification of the patients at increased risk of falls should be a component of the standard practice.

Aberrant cytokine and VCAM-1 expression in patients with viral and non-viral related liver cirrhosis.

The study aim was to compare the alterations in the expression levels of proinflammatory and chemotactic cytokines as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-17A and IL-8, the down regulatory cytokine IL-10, in addition to the vascular cell adhesion molecule-1 (VCAM-1) gene in different groups of patients with cirrhosis due to various etiologies. This case-control study included 84 patients suffering from cirrhosis of viral and non-viral etiologies and 20 sex and age-matched healthy controls. All patients were subjected to detailed history taking, clinical examination, and liver function assessment. The expression levels of TNF-α, IL-17A, IL-8, IL-10, and VCAM-1 were assessed in peripheral blood mononuclear cells by real-time PCR. Patients with cirrhosis showed marked changes in the tested gene expression levels relative to the control group. Higher expression levels of all genes except IL-10 were seen in patients of the viral than in the non-viral groups. Most of the significant correlations of liver function parameters were observed with TNF-α in both the viral and non-viral groups, followed by IL-17A. Increased TNF-α and IL-17A presented potential risk factors for disease progression to cirrhosis of Child class C.

Incidence and geographic characteristics of the population with osteoporotic hip fracture in Egypt- by the Egyptian Academy of Bone Health.

This work studies the epidemiology of hip fracture in Egypt. While the incidence of hip fracture in Egypt matches that of the Mediterranean region, there was geographic variation in osteoporotic hip fracture incidence between the north and south of Egypt. PURPOSE: To assess the incidence of hip fracture in Egypt, with special emphasis on the geographic and demographic variation among the Egyptian population. METHODS: The incidence of hip fractures treated in two Egyptian FLS centers was calculated for the period of February 2022-February 2023. Demographic information was recorded for every patient on the national register. All patients completed a baseline questionnaire, had clinical evaluation, fracture risk, falls, and sarcopenia risk assessment. A DXA scan was carried out for every patient. RESULTS: The annual incidence of low-energy hip fracture in individuals aged 40 years or more in Egypt in 2022-2023 was 123.34 per 100,000 in women and 55.19 per 100,000 in men. The incidence of hip fractures was higher in south Egypt (113.62) versus north Egypt (64.8). This was consistent for both genders. Bone mineral density was significantly (p < 0.01) lower in south Egypt at both the spine, distal forearm, as well as hip trochanters, whereas there was no significant difference between both locations in terms of the total hip and neck of the femur. Yet, falls risk, sarcopenia, as well as functional disability rates were significantly (p < 0.001) higher in the north. CONCLUSION: In Egypt, the hip fracture incidence was higher in the south compared to the north. Several modifiable factors contribute to fragility fracture risk independent of BMD, creating complex interrelationships between BMD, risk factors, and fracture risk.

Development of outcome measures for giant cell arteritis for use in clinical trials and standard practice.

BACKGROUND: Developments in outcome measures in the rheumatic diseases are promoted by the development of successful treatments. Giant cell arteritis (GCA) is a multifaceted disorder and, therefore, measurement of multiple outcomes is relevant to this illness. It is a privilege to analyze and monitor/transfer long-term patients' management outcomes particularly if the same outcomes are used in practice and in trials. OBJECTIVE: To classify the outcome measures for GCA with a discriminative ability to identify the disease activity status and response to therapy. METHODS: This study was composed of two steps, instrument design (item generation) and judgmental evidence. A panel of 13 experts was used to validate the instrument through quantitative (content validity) and qualitative (cognitive interviewing) methods. Content validity index was used to assess content validity quantitatively. RESULTS: Five items achieved high content validity where item-content validity index score was >0.79, and in the meantime achieved high content validity response score reflecting greater agreement among panel members. Through qualitative methods, items were improved until saturation was achieved. This agreed with the expert panel ranking of the items included in GCA disease outcome measures set. CONCLUSION: For daily clinical practice, outcome measures should reflect the patients' disease activity status and have to be easily assessed and recorded. The study identified composite outcome measures for GCA able to assess the disease state and monitor response to therapy. Key Points • Despite the cohort studies published in giant cell arteritis (GCA), there are no fully validated outcome measures for use in standard practice or clinical trials. • There is a gap in international standards for assessing GCA disease activity. • Identifying disease specific outcome measures is vital for monitoring response to therapy, treatment case series and therapeutic clinical trials in GCA. • This study was carried out aiming to classify the outcome measures for GCA with a discriminative ability to identify the disease activity status and response to therapy.

Osteoporosis treatment gap in patients at risk of fracture in Egypt: a multi-center, cross-sectional observational study.

Despite the wide availability of a wide variety of approved osteoporosis medications and DXA scan centers in Egypt, only a minority of patients at high risk of sustaining a fragility fracture receive treatment, even after their first fracture. Such big "treatment gap" leaves the most high-risk individuals unprotected against fragility fractures. This study provides a benchmark to monitor national trends in osteoporosis management and service uptake. PURPOSE: To assess the treatment gap among men and postmenopausal women presenting with a fragility fracture, and to analyze the characteristics and fracture risks of the patients presenting with an index fragility fracture. METHODS: This was a multi-center, cross-sectional, observational study. Both men and postmenopausal women, admitted with an osteoporotic fracture (whether major osteoporosis or hip fracture), were consecutively recruited for this work. The fracture risk was assessed based on their FRAX calculation prior to the index fracture. All the patients were assessed for their falls and sarcopenia risks. Blood tests for bone profile as well as DXA scan were offered to all the patients. RESULTS: Two hundred and thirty-six patients presenting with fragility fractures were included in this work. 70.8% were women and 29.2% were men. Mean age was 70.1 (SD = 9.2) years. Ten-year probability of fracture (without BMD) was high in 65.9% of the postmenopausal women and 40.3% of the men. 82.1% of the postmenopausal women and 100% in men identified to be eligible for osteoporosis therapy did not receive any form of osteoporosis therapy. FRAX score correlated significantly with bone mineral density assessment at both hip and spine. Falls, sarcopenia, and functional disability showed significant relation to the fracture risk. CONCLUSIONS: There is a large treatment gap in Egyptian older adults. The recent guidelines for osteoporosis management in Egypt endorsed fracture centric approach to identify people at risk. The gap appears to be related to a low rate of osteoporosis diagnosis and lack of patient education.

Association between Interleukin-17F 7488A/G and 7383A/G polymorphisms and susceptibility to juvenile idiopathic arthritis.

BACKGROUND: Interleukin-17F (IL-17F), one of the cytokines, is crucial in the pathophysiology of juvenile idiopathic arthritis (JIA). Therefore, we aimed to determine the relation between IL17F 7488A/G and IL17F 7383A/G single-nucleotide polymorphisms and JIA susceptibility and to explain their impact on the disease activity. METHODS: Genomic DNA of 70 patients with JIA and 70 age and sex-matched controls were extracted and typed for IL17F 7488A/G and IL17F 7383A/G single-nucleotide polymorphisms, using polymerase chain reaction with sequence-specific primers method, and compared between patients and controls. RESULTS: When compared to AA participants, children with the AG genotype of the IL17F 7488A/G and IL17F 7383A/G polymorphisms showed a substantially greater risk of JIA. Furthermore, children with the G allele were 2.8 folds more likely to have JIA than the A allele for IL17F 7488A/G polymorphism and 3.72 folds for IL17F 7383A/G polymorphism. Children with AG genotype of IL17F 7383A/G polymorphism were far more likely to have high activity JIA. CONCLUSIONS: The G allele of both IL17F 7488A/G and IL17F7383 A/G polymorphisms is associated with increased JIA susceptibility, and JIA at High Disease Activity was more likely to develop in AG subjects of the IL17F 7383 A/G polymorphism. IMPACT: The relationship between Interleukin-17F 7488A/G and 7383A/G polymorphisms and risk for JIA has not been recognized before. Impact of Interleukin-17F 7488A/G and 7383A/G genotypes on JIA disease activity. The G allele of both IL17F 7488A/G and IL17F7383 A/G polymorphisms are associated with increased JIA susceptibility. AG genotype of Interleukin-17F 7383 A/G polymorphism compared to AA patients, had a higher probability of developing JIA at a High Disease Activity (HDA) level.

A Case of Postcoronavirus Disease 2019 Antineutrophil Cytoplasmic Antibody-associated Vasculitis Successfully Treated with Rituximab.

We report a case of a 69-year-old Caucasian male with a history of hypertension, Type 2 diabetes, and Stage IIIa chronic kidney disease (CKD), who presented to the emergency department with positional dizziness, generalized weakness, weight loss, and suppressed appetite. Two months earlier, the patient was diagnosed with coronavirus disease 2019 (COVID-19). The patient had non-oliguric acute kidney injury alongside preexisting CKD. The urinalysis showed hematuria and significant non-nephrotic proteinuria. His serological markers were positive for antineutrophil cytoplasmic antibodies with high titers. A kidney biopsy showed focal crescentic glomerulonephritis of the pauci-immune type. Initially, treatment with immunosuppressive medication was deferred because the biopsy findings suggested a poor renal outcome, as the cortical sample showed tubular atrophy and interstitial fibrosis of more than 50%. The patient was discharged but was later readmitted with worsening renal function, deep venous thrombosis in the lower extremities, and patchy lung consolidation suggesting possible pneumonia, which was ruled out. He required dialysis and brief empiric antibiotics for pneumonia, and anticoagulation for deep venous thrombosis, and was treated with intravenous (IV) pulsed steroids, followed by gradually tapering oral steroids and rituximab induction therapy. He continued dialysis three times a week. Three months after discharge, his renal function improved to near-baseline level, and he no longer required hemodialysis. He continues to be on maintenance IV rituximab therapy and low-dose oral steroids and is followed closely by a rheumatologist. Our case reflects the evolving state of understanding how COVID-19 impacts the immune system, its varying manifestations, and its management.

Consensus Evidence-Based Clinical Practice Recommendations for the Diagnosis and Treat-To-Target Management of Osteoporosis in Chronic Kidney Disease Stages G4-G5D and Post-transplantation: An Initiative of Egyptian Academy of Bone Health.

Objective: The aim of this study was to reach a consensus on an updated version of the recommendations for the diagnosis and Treat-to-Target management of osteoporosis that is effective and safe for individuals with chronic kidney disease (CKD) G4-G5D/kidney transplant. Methods: Delphi process was implemented (3 rounds) to establish a consensus on 10 clinical domains: (1) study targets, (2) risk factors, (3) diagnosis, (4) case stratification, (5) treatment targets, (6) investigations, (7) medical management, (8) monitoring, (9) management of special groups, (10) fracture liaison service. After each round, statements were retired, modified, or added in view of the experts' suggestions, and the percent agreement was calculated. Statements receiving rates of 7-9 by more than 75% of experts' votes were considered as achieving consensus. Results: The surveys were sent to an expert panel (n = 26), of whom 23 participated in the three rounds (2 were international experts and 21 were national). Most of the participants were rheumatologists (87%), followed by nephrologists (8.7%), and geriatric physicians (4.3%). Eighteen recommendations, categorized into 10 domains, were obtained. Agreement with the recommendations (rank 7-9) ranged from 80 to 100%. Consensus was reached on the wording of all 10 clinical domains identified by the scientific committee. An algorithm for the management of osteoporosis in CKD has been suggested. Conclusion: A panel of international and national experts established a consensus regarding the management of osteoporosis in CKD patients. The developed recommendations provide a comprehensive approach to assessing and managing osteoporosis for all healthcare professionals involved in its management.

New perspectives for fascioliasis in Upper Egypt's new endemic region: Sociodemographic characteristics and phylogenetic analysis of Fasciola in humans, animals, and lymnaeid vectors.

BACKGROUND: Fascioliasis is a significant vector-borne disease that has emerged in numerous tropical and subtropical countries causing severe health problems. Egypt is one of the fascioliasis endemic regions; however, the current situation in Upper Egypt is understudied, with only sporadic human cases or outbreaks. This study aims to highlight the sociodemographic characteristics of human fascioliasis in a newly emerged endemic area in Upper Egypt, along with risk factors analysis and the molecular characteristics of the fasciolid population in humans, animals, and lymnaeid snails. METHODOLOGY/PRINCIPAL FINDINGS: The study reported Fasciola infection in patients and their close relatives by analyzing the risk of human infection. Morphological and molecular characterization was performed on lymnaeid snails. Multigene sequencing was also used to characterize fasciolids from human cases, cattle, and pooled snail samples. The study identified asymptomatic Fasciola infection among family members and identified the presence of peridomestic animals as a significant risk factor for infection. This is the first genetic evidence that Radix auricularia exists as the snail intermediate host in Egypt. CONCLUSIONS/SIGNIFICANCE: This study revealed that Assiut Governorate in Upper Egypt is a high-risk area for human fascioliasis that requires additional control measures. Fasciola hepatica was the main causative agent infecting humans and snail vectors in this newly emerged endemic area. In addition, this is the first report of R. auricularia as the snail intermediate host transmitting fascioliasis in Upper Egypt. Further research is required to clarify the widespread distribution of Fasciola in Egypt's various animal hosts. This provides insight into the mode of transmission, epidemiological criteria, and genetic diversity of fasciolid populations in Upper Egypt.\.

Association of Uric Acid-Lowering Therapy With Incident Chronic Kidney Disease.

Importance: Uric acid is a waste metabolite produced from the breakdown of purines, and elevated serum uric acid levels are associated with higher risk of hypertension, cardiovascular disease, and mortality and progression of chronic kidney disease (CKD). Treatment of hyperuricemia in patients with preexisting CKD has not been shown to improve kidney outcomes, but the associations of uric acid-lowering therapies with the development of new-onset kidney disease in patients with estimated glomerular filtration rate (eGFR) within reference range and no albuminuria is unclear. Objective: To examine the association of initiating uric acid-lowering therapy with the incidence of CKD. Design, Setting, and Participants: This cohort study included patients with eGFR of 60 mL/min/1.73 m2 or greater and no albuminuria treated at US Department of Veterans Affairs health care facilities from 2004 to 2019. Clinical trial emulation methods, including propensity score weighting, were used to minimize confounding. Data were analyzed from 2020 to 2022. Exposure: Newly started uric acid-lowering therapy. Main Outcomes and Measures: The main outcomes were incidences of eGFR less than 60 mL/min/1.73 m2, new-onset albuminuria, and end-stage kidney disease. Results: A total of 269 651 patients were assessed (mean [SD] age, 57.4 [12.5] years; 252 171 [94%] men). Among these, 29 501 patients (10.9%) started uric acid-lowering therapy, and 240 150 patients (89.1%) did not. Baseline characteristics, including serum uric acid level, were similar among treated and untreated patients after propensity score weighting. In the overall cohort, uric acid-lowering therapy was associated with higher risk of both incident eGFR less than 60 mL/min/1.73 m2 (weighted subhazard ratio [SHR], 1.15 [95% CI, 1.10-1.20; P < .001) and incident albuminuria (SHR, 1.05 [95% CI, 1.01-1.09; P < .001) but was not associated with the risk of end-stage kidney disease (SHR, 0.96 [95% CI, 0.62-1.50]; P = .87). In subgroup analyses, the association of uric acid-lowering therapy with worse kidney outcomes was limited to patients with baseline serum uric acid levels of 8 mg/dL or less. Conclusions and Relevance: These findings suggest that in patients with kidney function within reference range, uric acid-lowering therapy was not associated with beneficial kidney outcomes and may be associated with potential harm in patients with less severely elevated serum uric acid levels.

The Emerging Era of Interventional Imaging in Rheumatology: An Overview During the Coronavirus Disease-2019 (COVID-19) Pandemic.

Imaging has long been taking its place in the diagnosis, monitor, and prognosis of rheumatic diseases. It plays a vital role in the appraisal of treatment. Key progress in the clinical practice of rheumatology is the innovation of advanced imaging modalities; such as musculoskeletal ultrasound (MSUS), computerized tomography (CT) and magnetic resonance imaging (MRI). These modalities introduced a promising noninvasive method for visualizing bone and soft tissues to enable an improved diagnosis. The use of MSUS in rheumatology is considered a landmark in the evolution of the specialty and its ease of use and many applications in rheumatic diseases make it a forerunner instrument in the practice. The use of MSUS among rheumatologists must parallel the development rate of the excellence revealed in the specialty. Moreover, innovative interventional imaging in rheumatology (III-R) is gaining fame and key roles in the near future for a comprehensive management of rheumatic diseases with precision. This review article throws light on the emergence of these robust innovations that may reshape the guidelines and practice in rheumatology, in particular, efforts to enhance best practice during the coronavirus disease 2019 (COVID-19) pandemic are endorsed.

Assessment of Lupus Nephritis in a Multicenter Retrospective Egyptian Cohort: Initial Characteristics, Influence of Age and Gender, Outcome, and Potential Association with Disease Damage.

The study aimed to evaluate the association of demographic, clinical, and histopathologic characteristics with renal and disease outcomes. Persistent lack of partial or complete remission despite sequential induction therapy, chronic kidney disease (CKD) or endstage renal disease (ESRD), and/or mortality were determined as poor renal outcomes. Disease damage was investigated through the Systemic Lupus International Collaborating Clinics/ American College of Rheumatology Damage Index (SDI). Of 201 biopsy-proven lupus nephritis patients, a poor outcome was present in 56 (27.9%) patients, with nine (4.5%), 22 (10.9%), and 29 (14.4%) patients demonstrating lack of response, CKD, and ESRD, respectively, and the prevalence of mortality was 5.5% (11/201). The outcome was poor among males [29/201 (14.4%)] [P = 0.008; odds ratio (OR): 2.8; 95% confidence interval (CI): 1.2-6.4], yet comparable between adult- and juvenile-onset patients [80/201 (39.8%) (≤16 years)] (P = 0.6; OR: 0.8; 95% CI: 0.4-1.6). Hypertension (P <0.001; OR: 6.3; 95% CI: 2.6-14.9), elevated creatinine (P <0.001; OR: 5.2; 95% CI: 2.6-10.3), and hematuria (P <0.001; OR: 3.7; 95% CI: 1.9-7.5) at presentation, and fibrinoid necrosis [P <0.001; odds ratio (OR): 4.1; 95% confidence interval (CI): 2.1-8.1], wire loops (P = 0.006; OR: 2.4; 95% CI: 1.2-4.6), crescents (P <0.001; OR: 5.4 95% CI: 2.8-10.5), interstitial fibrosis (P = 0.001; OR: 2.7; 95% CI: 1.4-5.1), and acute vascular lesions (P = 0.004; OR: 3.6; 95% CI: 1.4-9.4) on biopsy were associated with a poor outcome. Chronic glomerular (P = 0.003) and acute vascular lesions (P <0.001), and a higher chronicity index (r = 0.1; P = 0.006) on biopsy, and frequent renal (r = 0.3; P <0.001) and extra-renal flares (r = 0.2; P <0.001) were associated with higher SDI scores. Among the studied renal and extra-renal parameters, independent predictors of higher disease damage solely included frequent renal flares (ᵝ= 1; P <0.001). To conclude, a poor renal outcome (27.9%) was associated with distinct features. Disease damage was associated with frequent renal flares.

Consensus evidence-based recommendations for treat-to-target management of immunoglobulin A vasculitis.

IgA vasculitis (IgAV), formerly known as Henoch-Schönlein purpura, is the most common cause of systemic vasculitis in childhood. Given its potential life-threatening systemic complications, early and accurate diagnosis as well as management of IgAV represent a major challenge for health care professionals. This study was carried out to attain an evidence-based expert consensus on a treat-to-target management approach for IgAV using Delphi technique. The preliminary scientific committee identified a total of 16 key clinical questions according to the patient, intervention, comparison, and outcomes (PICO) approach. An evidence-based, systematic, literature review was conducted to compile evidence for the IgAV management. The core leadership team identified researchers and clinicians with expertise in IgAV management in Egypt upon which experts were gathered from different governorates and health centers across Egypt. Delphi process was implemented (two rounds) to reach a consensus. An online questionnaire was sent to expert panel (n = 26) who participated in the two rounds. After completing round 2, a total of 20 recommendation items, categorized into two sections were obtained. Agreement with the recommendations (rank 7-9) ranged from 91.7-100%. Consensus was reached (i.e. ⩾75% of respondents strongly agreed or agreed) on the wording of all the 20 clinical standards identified by the scientific committee. Algorithms for the diagnosis and management have been suggested. This was an expert, consensus recommendations for the diagnosis and treatment of IgAV and IgA vasculitic nephritis, based on best available evidence and expert opinion. The guideline presented a strategy of care with a pathway to achieve a state of remission as early as possible. PLAIN LANGUAGE SUMMARY: Given its potential life-threatening systemic complications, early and accurate diagnosis of immunoglobulin A vasculitis represents a major challenge for health care professionals. This work provided cornerstone principles for the management of the condition. Adopting PICO approach and implementing Delphi process a consensus was reached on evidence-based treat-to-target treatment recommendations. This will endorse enhancement and consistency of care of this cohort of patients in standard practice.

Consensus evidence-based clinical practice guidelines for the diagnosis and treat-to-target management of osteoporosis in Africa: an initiative by the African Society of Bone Health and Metabolic Bone Diseases.

The objective of this consensus statement is to inform the clinical practice communities, research centres and policymakers across Africa of the results of the recommendations for osteoporosis prevention, diagnosis and management. The developed guideline provides state-of-the-art information and presents the conclusions and recommendations of the consensus panel regarding these issues. PURPOSE: To reach an African expert consensus on a treat-to-target strategy, based on current evidence for best practice, for the management of osteoporosis and prevention of fractures. METHOD: A 3-round Delphi process was conducted with 17 osteoporosis experts from different African countries. All rounds were conducted online. In round 1, experts reviewed a list of 21 key clinical questions. In rounds 2 and 3, they rated the statements stratified under each domain for its fit (on a scale of 1-9). After each round, statements were retired, modified or added in view of the experts' suggestions and the percent agreement was calculated. Statements receiving rates of 7-9 by more than 75% of experts' votes were considered as achieving consensus. RESULTS: The developed guidelines adopted a fracture risk-centric approach. Results of round 1 revealed that of the 21 proposed domains, 10 were accepted whereas 11 were amended. In round 2, 32 statements were presented: 2 statements were retired for similarity, 9 statements reached consensus, whereas modifications were suggested for 21 statements. After the 3rd round of rating, the experts came to consensus on the 32 statements. Frequency of high-rate recommendation ranged from 83.33 to 100%. The response rate of the experts was 100%. An algorithm for the osteoporosis management osteoporosis was suggested. CONCLUSION: This study is an important step in setting up a standardised osteoporosis service across the continent. Building a single model that can be applied in standard practice across Africa will enable the clinicians to face the key challenges of managing osteoporosis; furthermore, it highlights the unmet needs for the policymakers responsible for providing bone health care together with and positive outcomes of patients' care.

Is there a potential dual effect of denosumab for treatment of osteoporosis and sarcopenia?

BACKGROUND: The prevalence of sarcopenia with osteoporosis results in a higher risk of falling and fractures. It was noted that patients who had completed their planned 5-year denosumab therapy course as treatment for these conditions started to sustain falls. PURPOSE: To assess (a) whether denosumab has a unique dual effect on both bone and muscle in comparison to other anti-resorptive agents and (b) its effectiveness in the follow-up period post-treatment completion compared to other anti-resorptive agents. METHOD: One hundred thirty-five patients diagnosed to have postmenopausal/senile osteoporosis and who were prescribed denosumab were compared to a control group of 272 patients stratified into 2 subgroups - 136 prescribed alendronate and 136 prescribed zoledronate. All patients were assessed for: BMD (DXA), falls risk (FRAS), fracture risk (FRAX), and sarcopenia measures. All were re-assessed after 5 years of denosumab/alendronate therapy and 3 years of zoledronate and 1 year after stopping the osteoporosis therapy. RESULTS: No significant baseline demographic differences between the 3 groups. On completion of the 5-year denosumab therapy, there was significant decrease in falls risk (P = 0.001) and significant improvements in all sarcopenia measures (P = 0.01). One-year post-discontinuation of denosumab, a significant worsening of both falls risk and sarcopenia measures (P = 0.01) noticed. CONCLUSION: Denosumab displayed positive impact and significant improvements in BMD and sarcopenia measures. It also enhanced multidirectional agility as depicted by Timed Up and Go (TUG). Collectively, this would explain the reduction of falls risk which got worse on stopping the medication. Key points • The coexistence of osteoporosis and sarcopenia has been recently considered in some groups as a syndrome termed 'osteosarcopenia'. • Bone and muscle closely interact with each other not only anatomically, but also at the chemical and metabolic levels. • Denosumab displayed positive impact and significant improvements in all sarcopenia measures, and enhanced multidirectional agility with consequent reduction in falls risk. • Denosumab can be considered as a first osteoporosis therapeutic option in this group of patients presenting with osteosarcopenia manifestations.

Urinary soluble alpha chain of the interleukin-2 receptor as a biomarker of active lupus nephritis in Egyptian children with juvenile systemic lupus erythematosus.

OBJECTIVES: This study aims to assess the urinary soluble alpha chain of the interleukin-2 receptor (sCD25) concentrations in patients with juvenile systemic lupus erythematosus (JSLE) and to evaluate its validity to be a possible marker of disease activity in patients with lupus nephritis (LN). PATIENTS AND METHODS: We assessed sCD25 concentrations in urine samples obtained from 53 JSLE patients (15 males, 38 females; median age 11 years; range, 7 to 17 years) and 30 age- and sex-matched apparently healthy controls (10 males, 20 females; median age 10 years; range, 6 to 16 years). Concentrations were normalized according to urinary creatinine excretion. JSLE patients were subjected to clinical examination and assessment of overall disease activity by Systemic Lupus Erythematous Disease Activity Index (SLEDAI), while evaluation of LN activity was preformed using Systemic Lupus International Collaborating Clinics (SLICC) renal activity score. RESULTS: The JSLE patients had significantly higher normalized urinary sCD25 concentrations compared to the healthy controls (p=0.001). Patients with active LN had significantly higher normalized urinary sCD25 levels than active JSLE patients without LN (p=0.002) and JSLE patients with inactive disease (p<0.001). A significant positive correlation was found between normalized urinary sCD25 concentrations with different activity parameters such as proteinuria (p=0.004), SLEDAI (p<0.001), renal SLEDAI (p<0.001), and SLICC renal activity score (p<0.001). A significant negative correlation was found between urinary sCD25 and complement 3 (p<0.001). CONCLUSION: Urinary concentrations of sCD25 were significantly elevated in JSLE patients, particularly in those with active LN. The remarkable association between urinary sCD25 concentrations and different renal disease activity parameters implies that urinary sCD25 can be a beneficial marker to monitor active nephritis in JSLE patients.

Hypovitaminosis D in Patients with Ankylosing Spondylitis: Frequency and Consequences.

OBJECTIVES: This study aimed to assess the frequency of hypovitaminosis D in patients with Ankylosing Spondylitis (AS) compared to healthy controls and evaluate its association with disease activity, structural damage and Bone Mineral Density (BMD). METHODS: Serum 25(OH) D in 30 AS male patients was compared to 30 matched healthy controls. AS disease activity was assessed using AS Disease Activity Score and C - reactive protein (ASDAS- CRP). Bath AS Functional Index (BASFI) and Bath AS Metrology Index (BASMI) were used to assess the functional impairment and the spinal mobility, respectively. Radiological damage was scored according to modified Stoke AS Spine Score (mSASSS) and BMD was measured in the lumbar spine and femoral neck. RESULTS: The mean serum 25(OH)D levels in AS patients were significantly lower compared to healthy controls (27.73 ± 14.27 vs. 38.46 ± 8.11ng/ml, P <0.001). Among the patients, 60% exhibited hypovitaminosis D. AS patients with hypovitaminosis D had significantly higher ASDAS-CRP (p<0.001), BASFAI (p=0.0003) and mSASSS (p=0.04) scores. Additionally, BMD and Z scores at lumbar and femoral sites were significantly reduced in patients with hypovitaminosis D (P < 0.05). Serum 25(OH)D was positively correlated with BMD (lumbar and femoral; p=0.002 and p=0.01 respectively) and Z scores (lumbar and femoral; p<0.001and p=0.01 respectively), whereas, negatively correlated with ASDAS-CRP (p<0.001), BASFI (p<0.001), and mSASSS (p=0.003). ASDAS - CRP was the only significant predictor of hypovitaminosis D in AS patients. CONCLUSION: Hypovitaminosis D is prevalent among AS patients and is associated with increased risk of active disease, impaired function, radiographic severity and bone mineral loss. Future studies with a larger sample size are recommended to assess the impact of vitamin D deficiency on radiological progression in AS and to address whether or not vitamin D supplementation will help control the active disease.

Characteristics, evolution, and outcome of patients with non-infectious uveitis referred for rheumatologic assessment and management: an Egyptian multicenter retrospective study.

OBJECTIVE: To investigate the characteristics, evolution, and visual outcome of non-infectious uveitis. METHODOLOGY: Records of 201 patients with non-infectious uveitis (136 (67.7%) males and 84 (41.8%) juvenile-onset (≤ 16 years)) were retrospectively reviewed. Data were analyzed through Kruskal-Wallis and Mann-Whitney, chi-square (χ2) tests, and logistic regression. RESULTS: The median disease and follow-up durations were 36 (interquartile range (IQR) 24-70) and 24 (IQR 10-36) months, respectively. Fifty-eight (28.9%) patients had persistently idiopathic uveitis, and 143 (71.1%) were associated with rheumatic diseases, of whom uveitis heralded, coincided with, and succeeded the rheumatic manifestation(s) in 62/143 (43.4%), 37/143 (25.9%), and 44/143 (30.7%) patients, respectively. Established rheumatic diseases were Behçet's disease (103/201 (51.2%)), juvenile idiopathic arthritis (13/201 (6.5%)), sarcoidosis (8/201 (4%)), seronegative spondyloarthropathy (7/201 (3.5%)), and Vogt-Koyanagi-Harada (7/201 (3.5%)), and other diagnoses were present in 5/201 (2.5%) patients. Patients with idiopathic uveitis were characterized by a juvenile-onset (p < 0.001), lower male predominance (p = 0.01), prevalent granulomatous (p < 0.001), and anterior (p = 0.001) uveitis. The median visual acuity at last visit was 0.3 (IQR 0.05-0.6). Visual loss was present in 45/201 (22.3%) patients (36/201 (17.9%) unilateral and 9/201 (4.4%) bilateral). Apart from a longer disease duration (p = 0.002), lower educational level (p = 0.03), and prevalent panuveitis (p < 0.001), visual loss was not associated with any other studied ocular or extra-ocular characteristics. CONCLUSION: Behçet's disease (51.2%) and idiopathic uveitis (28.9%) were the most prevalent causes of non-infectious uveitis in our study. Visual loss (22.3%) was associated with a longer disease duration, lower education level, and prevalent panuveitis. Key Points • Most common causes of uveitis referred to rheumatologists were Behçet's disease and idiopathic uveitis. • Several rheumatic diseases initially presented only with uveitis, more commonly in adult and male patients. • Panuveitis was more frequent among patients with an established rheumatic disease, whereas granulomatous uveitis was uncommon. • Longer disease duration and presence of panuveitis were independently associated with visual loss.