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.

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.

Development and initial validation of a composite disease activity score for systemic juvenile idiopathic arthritis.

OBJECTIVE: To develop a composite disease activity score for systemic JIA (sJIA) and to provide preliminary evidence of its validity. METHODS: The systemic Juvenile Arthritis Disease Activity Score (sJADAS) was constructed by adding to the four items of the original JADAS a fifth item that aimed to quantify the activity of systemic features. Validation analyses were conducted on patients with definite or probable/possible sJIA enrolled at first visit or at the time of a flare, who had active systemic manifestations, which should include fever. Patients were reassessed 2 weeks to 3 months after baseline. Three versions were examined, including ESR, CRP or no acute-phase reactant. RESULTS: A total of 163 patients were included at 30 centres in 10 countries. The sJADAS was found to be feasible and to possess face and content validity, good construct validity, satisfactory internal consistency (Cronbach's alpha 0.64-0.65), fair ability to discriminate between patients with different disease activity states and between those whose parents were satisfied or not satisfied with illness outcome (P < 0.0001 for both), and strong responsiveness to change over time (standardized response mean 2.04-2.58). Overall, these properties were found to be better than those of the original JADAS and of DAS for RA and of Puchot score for adult-onset Still's disease. CONCLUSION: The sJADAS showed good measurement properties and is therefore a valid instrument for the assessment of disease activity in children with sJIA. The performance of the new tool should be further examined in other patient cohorts that are evaluated prospectively.

Ehrlichiosis infection mimicking thrombotic microangiopathy syndrome early after kidney transplantation.

Fever of unknown origin and the clinical picture of thrombotic microangiopathy (TMA) are diagnostic challenges in the early period after kidney transplantation. Here, we report a case of human monocytic ehrlichiosis in a renal allograft recipient who presented with fever and clinical picture of TMA in the first month post-kidney transplant. Despite broad coverage with multiple antimicrobial agents, fever and hematological abnormalities persisted for several days. A history of contact exposure and living in an endemic area raised clinical suspicion for human monocytic ehrlichiosis (HME), and empiric treatment with doxycycline was initiated. Definitive diagnosis of HME was confirmed by polymerase chain reaction (PCR) for Ehrlichia chaffeensis. Human ehrlichiosis should be considered within the differential diagnosis in kidney transplant recipients with the clinical picture of TMA and fever of unknown origin. Furthermore, early treatment with doxycycline enhances rapid resolution of clinical and laboratory recovery.

PTH assays in dialysis patients: Practical considerations.

Parathyroid hormone (PTH) 1-84 is the main biologically active hormone produced by the parathyroid cells. Circulating PTH molecules include the whole PTH 1-84 along with amino (N) and carboxyl (C) terminal fragments. While PTH is the best available noninvasive biomarker to assess bone turnover in dialysis patients, the biological roles of individual circulating PTH fragments are still not completely known. The understanding that there is an enormous variation in the target specificity of currently available PTH assays for different circulating forms of PTH has led to the evolution of assays from first to second then third generation. With a reduction in kidney function, there is a preferential increase in circulating C fragments and non-PTH 1-84 forms, resulting in a decrease in the ratio of PTH 1-84/non-PTH 1-84. However, there are also substantial differences in between-assay measurements, with several fold variations in results. Targets based on multiples of the upper limit of normal (ULN) should be used rather than PTH ranges using absolute iPTH values. To date, the second-generation PTH remains the most widely used assay. Current guidelines recommend following iPTH trends rather than absolute values. Herein, we highlight problems and challenges in PTH assays/measurements and their interpretations in dialysis patients.

Impact of human leukocyte antigen and calculated panel reactive antibody on BK viremia in kidney transplant recipients: A single-center experience and literature review.

BACKGROUND: The aim of this retrospective analysis was to investigate the effect of human leukocyte antigen (HLA) and calculated panel reactive antibody (cPRA) on BK virus activation as evidenced by BK viremia (BKV). PATIENTS AND METHODS: At our institution, 649 kidney transplant patients were screened for BKV from 2009 to 2017. Patients were considered to have BKV if they had >10 000 copies/mL of BK DNA in their blood. Donor and recipient HLA and cPRA, demographic, clinical and laboratory data, as well as immunosuppressive medications were collected. RESULTS: We identified 122 BK positive and 527 BK negative patients. Only 25% of the patients had cPRA of 20% or more, and 64% had more than three HLA-A, -B, and -DR mismatches. In both univariate and multivariate analyses, male gender, age, and maintenance of steroid therapy significantly increased the risk of BKV (P = 0.005, 0.005 and <0.001, respectively). The degree of cPRA and the individual HLA allele and HLA allele matching did not significantly affect BKV. CONCLUSION: Neither the degree of HLA mismatching nor cPRA appears to affect BKV. Moreover, no specific HLA allele, HLA allele matching, or cPRA were associated with BKV.

Vitamin E ameliorates alterations to the articular cartilage of knee joints induced by monoiodoacetate and diabetes mellitus in rats.

We recently reported an animal model of osteoarthritis (OA) induced by a combination of the chondrocyte glycolysis inhibitor, monoiodoacetate (MIA) and the agent that induces diabetes mellitus, streptozotocin (STZ). Here we investigated the potential protective effect of the antioxidant and anti-inflammatory agent, vitamin E against MIA+STZ-induced OA. Therefore, rats were either injected once with MIA (2 mg/50 µL) + 65 mg/kg STZ before being sacrificed after 8 weeks (model group) or were treated immediately after MIA+STZ injections with vitamin E (600 mg/kg; thrice a week) before being sacrificed after 8 weeks (treatment group). Using scanning and transmission electron microscopy examinations, we observed in the model group a substantial damage to the articular cartilage of the knee joint as demonstrated by the destruction of the chondrocytes, territorial matrix, disrupted lacunae, collagen fibers, and profound chondrocyte ultrastructural alterations such as degenerated chondrocyte, irregular cytoplasmic membrane, damaged mitochondria and rough endoplasmic reticulum, vacuolated cytoplasm, presence of lipid droplets and different sizes of lysosomes, which were substantially but not completely protected by vitamin E. H&E stained sections of knee joint articular cartilage showed that MIA+STZ induced damage to the chondrocyte and territorial matrix. Vitamin E also significantly (p < .05) inhibited MIA+STZ-induced blood levels of the inflammatory biomarkers, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) that are known to be modulated in OA and diabetes. We conclude that vitamin E protects against MIA+STZ-induced knee joints injuries in rats, which is associated with the inhibition of biomarkers of inflammation.

Clinical Research Recession: Training Needs Perception Among Medical Students.

Clinical research is an integrated part of medical education. There is a noticeable decrease in the number of physician-scientists in developing countries, which is reflected by a decrease in research output and publications from these countries. We conducted a survey aiming to identify the gaps in clinical research training from the perspective of medical students. The results can be used to customize future clinical research trainings. The survey tool was divided into six modules which represent the cornerstones of clinical research based on similar surveys done for the same purpose. For each module, questions covered the perceived knowledge of its aspects and how much relevant the responder thought it was to clinical research. Five hundred one candidates have filled the survey. Evidence-based medicine (EBM) had the highest knowledge score of 2.20/4, while "clinical trials execution" knowledge got the lowest score of 1.64/4. Responders perceived EBM as the most relevant aspect of clinical research (3.39/4), while research ethics received the lowest score 3.18/4. "Clinical trials execution" had the largest gap of a difference calculated as 1.60, while EBM had the lowest gap of 1.20. More attention must be paid to clinical research training for medical students in developing countries. These trainings have to be customized to focus on clinical trial execution, research methodology, and biostatistics. In parallel, awareness campaigns targeted toward the medical community emphasizing the importance of the ethics as an aspect of clinical research should be established.

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.

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.

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.

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.

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.

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.

Acceptability and preliminary feasibility of an internet/CD-ROM-based education and decision program for early-stage prostate cancer patients: randomized pilot study.

BACKGROUND: Prostate cancer is the most common cancer affecting men in the United States. Management options for localized disease exist, yet an evidence-based criterion standard for treatment still has to emerge. Although 5-year survival rates approach 98%, all treatment options carry the possibility for significant side effects, such as erectile dysfunction and urinary incontinence. It is therefore recommended that patients be actively involved in the treatment decision process. We have developed an Internet/CD-ROM-based multimedia Prostate Interactive Educational System (PIES) to enhance patients' treatment decision making. PIES virtually mirrors a health center to provide patients with information about prostate cancer and its treatment through an intuitive interface, using videos, animations, graphics, and texts. OBJECTIVES: (1) To examine the acceptability and feasibility of the PIES intervention and to report preliminary outcomes of the program in a pilot trial among patients with a new prostate cancer diagnosis, and (2) to explore the potential impact of tailoring PIES treatment information to participants' information-seeking styles on study outcomes. METHODS: Participants (n = 72) were patients with newly diagnosed localized prostate cancer who had not made a treatment decision. Patients were randomly assigned to 3 experimental conditions: (1) control condition (providing information through standard National Cancer Institute brochures; 26%), and PIES (2) with tailoring (43%) and (3) without tailoring to a patient's information-seeking style (31%). Questionnaires were administrated before (t1) and immediately after the intervention (t2). Measurements include evaluation and acceptability of the PIES intervention, monitoring/blunting information-seeking style, psychological distress, and decision-related variables (eg, decisional confidence, feeling informed about prostate cancer and treatment, and treatment preference). RESULTS: The PIES program was well accepted by patients and did not interfere with the clinical routine. About 79% of eligible patients (72/91) completed the pre- and post-PIES intervention assessments. Patients in the PIES groups compared with those in the control condition were significantly more likely to report higher levels of confidence in their treatment choices, higher levels of helpfulness of the information they received in making a treatment decision, and that the information they received was emotionally reassuring. Patients in the PIES groups compared with those in the control condition were significantly less likely to need more information about treatment options, were less anxious about their treatment choices, and thought the information they received was clear (P < .05). Tailoring PIES information to information-seeking style was not related to decision-making variables. CONCLUSIONS: This pilot study confirms that the implementation of PIES within a clinical practice is feasible and acceptable to patients with a recent diagnosis of prostate cancer. PIES improved key decision-making process variables and reduced the emotional impact of a difficult medical decision.

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.

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.

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.

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.