YKL-40 in serum: a promising biomarker of juvenile SLE and strongly correlated with disease duration.

BACKGROUND: The biological function of YKL-40 is not well determined in different inflammatory and autoimmune diseases; however, some data highlighted its possible connection with disease activity. AIM: We investigated the diagnostic utility of serum YKL-40 in patients with SLE and examined its correlation with disease activity. Additionally, we examined any differences in serum YKL-40 levels between juvenile and adult SLE patients. METHODS: We included 78 female patients with SLE and 42 controls. The level of YKL-40 in serum was measured by ELISA. RESULTS: The serum YKL-40 level in SLE patients was significantly higher compared to the control group (9 (3) ng/mL vs. 5.5 (0.1) ng/mL; p < 0.001). YKL-40 showed excellent diagnostic utility with an AUC of 1 (p < 0.001) and a cutoff point of 5.6, providing sensitivity and specificity of 100%. YKL-40 was higher in adolescents and those with a positive family history of SLE (p = 0.01 for both) and positively correlated with disease duration (r = 0.45, p < 0.001). YKL-40 level was significantly higher in patients with photosensitivity, fever, vasculitis, blood disorders, positive anti-dsDNA, and APL ab (p < 0.05 for all). Conversely, patients with skin manifestations had a significantly lower YKL-40 (p = 0.004). In juvenile SLE, the AUC was 0.65 and a p-value of 0.01, and at a cutoff value of (8.7) ng/mL, the sensitivity and specificity were 72% and 60%, respectively. CONCLUSION: YKL-40 in serum could be a promising biomarker in patients with SLE, especially in adolescent-onset cases. It is independently influenced by disease duration, anemia, thrombocytopenia, positive anti-dsDNA, and APL ab features.

Evaluation of Immunity-related GTPase Family M Protein (IRGM) SNPs among Egyptian Lupus Patients: A Case-control Study.

OBJECTIVE: One of the potential factors that cause systemic lupus erythematosus (SLE) development is autophagy. Immunity-related GTPase family M protein (IRGM) has been shown to be linked to immune-mediated diseases. The aim of the current study was to assess the role of the IRGM-autophagy gene in SLE susceptibility in an Egyptian population and its relation to lupus nephritis. METHODS: A case-control study was conducted in which a total of 200 subjects (100SLE and 100 healthy controls) were enrolled. Two single-nucleotide polymorphisms (SNPs) (rs10065172 and rs4958847) were genotyped. Genotypes and alleles analysis was conducted to compare between cases and controls, as well as a stratification analysis was conducted on the presence or absence of lupus nephritis. RESULTS: Among selected SNPs of IRGM, no association was found between both SNPs and SLE susceptibility. For rs10065172, the major expressed genotype was CC (61% and 71%) (Adj OR= 2.9, 95%= 0.545-15.5), followed by TC (34% and 27%) (Adj OR= 1.985, 95% = 0.357-11.041) in cases and controls, respectively. For rs4958847, AA and AG were comparably expressed in case [(43% and 39%) (Adj OR= 1.073, 95% = 0.483-2.382)] and control [(41% and 43%) (Adj OR= 1.24, 95% = 0.557- 2.763)], respectively. Additionally, no relationship among both SNPs and gender, lupus nephritis, disease activity, or disease duration, was observed. CONCLUSION: IRGM SNPs (rs10065172 and rs4958847) expression was comparable among SLE patients and controls of the Egyptian cohort. Genotype and allele frequency of IRGM SNPs did not differ in lupus nephritis and non-lupus nephritis patients.

Role of endoscopic ultrasound and cyst fluid tumor markers in diagnosis of pancreatic cystic lesions.

BACKGROUND: Pancreatic cystic lesions (PCLs) are common in clinical practice. The accurate classification and diagnosis of these lesions are crucial to avoid unnecessary treatment of benign lesions and missed opportunities for early treatment of potentially malignant lesions. AIM: To evaluate the role of cyst fluid analysis of different tumor markers such as cancer antigens [e.g., cancer antigen (CA)19-9, CA72-4], carcinoembryonic antigen (CEA), serine protease inhibitor Kazal-type 1 (SPINK1), interleukin 1 beta (IL1-ß), vascular endothelial growth factor A (VEGF-A), and prostaglandin E2 (PGE2)], amylase, and mucin stain in diagnosing pancreatic cysts and differentiating malignant from benign lesions. METHODS: This study included 76 patients diagnosed with PCLs using different imaging modalities. All patients underwent endoscopic ultrasound (EUS) and EUS-fine needle aspiration (EUS-FNA) for characterization and sampling of different PCLs. RESULTS: The mean age of studied patients was 47.4 ± 11.4 years, with a slight female predominance (59.2%). Mucin stain showed high statistical significance in predicting malignancy with a sensitivity of 87.1% and specificity of 95.56%. It also showed a positive predictive value and negative predictive value of 93.1% and 91.49%, respectively (P < 0.001). We found that positive mucin stain, cyst fluid glucose, SPINK1, amylase, and CEA levels had high statistical significance (P < 0.0001). In contrast, IL-1ß, CA 72-4, VEGF-A, VEGFR2, and PGE2 did not show any statistical significance. Univariate regression analysis for prediction of malignancy in PCLs showed a statistically significant positive correlation with mural nodules, lymph nodes, cyst diameter, mucin stain, and cyst fluid CEA. Meanwhile, logistic multivariable regression analysis proved that mural nodules, mucin stain, and SPINK1 were independent predictors of malignancy in cystic pancreatic lesions. CONCLUSION: EUS examination of cyst morphology with cytopathological analysis and cyst fluid analysis could improve the differentiation between malignant and benign pancreatic cysts. Also, CEA, glucose, and SPINK1 could be used as promising markers to predict malignant pancreatic cysts.

Sarcoidosis beyond pulmonary involvement: A case series of unusual presentations.

Unusual presentations of sarcoidosis pose a diagnostic challenge and warrant attention. Hematologic associations: Case 1 (37-years-old male): Pancytopenia: myelofibrosis (leading to sepsis and mortality) following a two-year quiescent course of biopsy-proven-sarcoidosis. Case 2 : (38-years-old male): Presentation with thrombocytopenia (5 × 103/cmm): immune thrombocytopenic purpura (histologically associated with megakaryocytic emperipolesis). Biopsied enlarged lymph nodes demonstrated sarcoidosis. Hematologic sarcoid involvement is usually due to granulomatous bone marrow (3.9%) or splenic infiltration (6-30%); however, the presented manifestations are scarcely reported with a potential significance that is yet to be elucidated. Case 3: Neurologic presentation: 48-years-old female: presentation with bilateral sensorineural hearing loss and facial palsy. Brain magnetic resonance imaging showed leptomeningeal thickening. Biopsied enlarged lymph nodes showed sarcoidosis. Case 4: Neurologic and renal manifestations: 13-years-old male (family history of sarcoidosis): Presenting with acute headache, investigations showed elevated serum creatinine (2.1 mg/dL) and angiotensin converting enzyme, and computed tomography chest and abdominal findings characteristic of sarcoidosis. Associated benign increased intracranial and acute tubulointerstitial nephritis (with eosinophils) were diagnosed upon concordant workup. Of sarcoidosis neurologic affection (5-10%), cranial nerve(s) involvement is among the most common (25-50% of neurosarcoid affection), particularly that of the facial nerve (Case 3). Leptomeningeal enhancement is among the most common neurosarcoid radiologic findings (30-40%). Whereas benign increased intracranial tension (Case 4) is much less reported. Among sarcoidosis renal involvement (35-50%), interstitial nephritis usually presents with granulomatous renal lesions, yet its sole association with sarcoidosis is unusual (Case 4). The portrayed atypical hematologic, neurologic, and renal manifestations further emphasize the masquerading nature of sarcoidosis.

Impact of Combined Photo-Biomodulation and Aerobic Exercise on Cognitive Function and Quality-of-Life in Elderly Alzheimer Patients with Anemia: A Randomized Clinical Trial.

PURPOSE: Few data are available on the positive impact of photo-biomodulation (PBM) using low-level laser therapy as a complementary treatment for improving the cognitive function and optimizing the hemoglobin (Hb) level and oxygen carrying capacity in anemic elderly patients and consequently improving the quality-of-life. The present study aimed to evaluate a new, safe, and easy therapeutic approach to improve Alzheimer's disease-related symptoms that interfere with the whole life activities and social interaction of elderly patients. PATIENTS AND METHODS: In this placebo-controlled clinical trial, 60 elderly patients suffering from anemia and mild cognitive dysfunction were randomly assigned into two equal groups to receive active or placebo low-level laser in addition to a moderate-intensity aerobic exercise over a 12-week period. Hb level as well as cognitive and functional tests were reassessed for any change after 12 weeks of intervention. RESULTS: By the end of this study, both groups showed significant improvements in Hb level, Montreal Cognitive Assessment Scale (MoCa - B basic), Quality-of-Life for Alzheimer's Disease scale, and Berg Balance scale scores along with significant reduction in body mass index (BMI) and waist-hip ratio (WHR) (P<0.0001). The experimental group which received active low-level laser in addition to moderate-intensity aerobic exercise showed more significant results compared to the control group which received placebo low-level laser in addition to moderate-intensity aerobic exercise in all the measured outcomes (P<0.001). CONCLUSION: Combined low-level laser therapy and moderate-intensity aerobic exercises are more effective in improving the cognitive function and quality-of-life of Alzheimer's disease patients. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT04496778.

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.

Value of Albumin-Fibrinogen Ratio and CRP-Albumin Ratio as Predictor Marker of Disease Activity in Egyptian RA Patients, Correlated with Musculoskeletal Sonography.

PURPOSE: To evaluate the albumin-fibrinogen ratio (AFR) and C-reactive protein-albumin ratio (CAR) as inflammatory markers in rheumatoid arthritis (RA) and to investigate their association with disease activity correlating with musculoskeletal ultrasonographic findings. PATIENTS AND METHODS: A total of 125 cases of RA patients were consecutively enrolled in a multicenter cross-sectional study compared to 100 healthy controls, all subjects were investigated for fibrinogen, albumin, CRP, erythrocyte sedimentation rate, AFR, and CAR measurements. Patients' disease activity was assessed by disease activity score (DAS28-ESR), and they were subjected to high-frequency ultrasound both in greyscale and power Doppler. RESULTS: RA patients had lower AFR and higher CAR than those in the control group (P < 0.001). A positive correlation was demonstrated between CAR and DAS score (r=0.589, P = 0.0001), whilst there was a precise negative correlation between AFR and DAS 28-ESR (r=-0.74, p<0.001). ROC curve analyses revealed fibrinogen showed the best sensitivity (92.1%) for the area under the curve of 0.928, at a criterion of 2.47, while AFR has an area under the curve of 0.826 with sensitivity and specificity (86.84% and 75%, respectively) at cut-off value 1.46. Actively diseased patients had elevated CAR than those in remission (P < 0.001). Patients with synovial thickening and bone erosions had lower AFR than those without, CAR was higher in patients with power doppler changes than those without (p=0.015). CONCLUSION: Higher CAR and lower AFR were expressed in active RA than those in remission. CAR and AFR could be useful markers of ongoing inflammation and joint affection detected by musculoskeletal ultrasonography.

Hyponatremia as an Inflammatory Marker of Lupus Activity Is a Fact or Fad: A Cross-Sectional Study.

PURPOSE: Systemic lupus erythematosus (SLE) is an autoimmune disease with multi-organ involvement. Hyponatremia is common in inflammatory diseases such as meningitis. Also, it has been found to be strongly associated with the degree of inflammation. However, it has not been fully evaluated in lupus. This study aimed to assess the inflammatory impact of hyponatremia in SLE patients and investigate its relationship with SLE disease activity. PATIENTS AND METHODS: A total of 101 patients with SLE were enrolled in this study and divided into two groups according to Na level; a normo-natremic group and a hyponatremic group. Demographic and clinical data were collected. SLE activity was assessed by the systemic lupus erythematosus disease activity index (SLEDAI). The estimated sedimentation rate (ESR) as well as levels of C-reactive protein (CRP) and complements (C3 and C4) were measured. RESULTS: The majority of patients were females (98 subjects) (97%) with a mean age of 33±8 years. Out of 101 participants, 40 patients (39.6%) were hyponatremic with a mean Na level of 131.58±3.11 mmol/L. There was a statistically negative correlation between both ESR and SLEADI score and Na level (r=-0.436 and -0.436, respectively) with p=0.002, whereas Na level was positively correlated with complements, Cl, and albumin levels (r=0.653, 0.314, and 0.460, respectively) (p=0.000, 0.027, and >0.001, respectively). CRP was not correlated with Na level. ESR was independently correlated with hyponatremia at the 95% CI for Exp B (0.997-0.058) with a p-value of 0.048. CONCLUSION: Hyponatremia could be used as an indicator of SLE activity. Also, it might be an easily and rapidly detected as well as a prognostically useful marker of inflammation.

Novel Application of the Traditional Lipid Ratios as Strong Risk Predictors of NASH.

PURPOSE: Limited data are available regarding the role of triglycerides, cholesterol and lipoproteins ratios as risk factors for nonalcoholic fatty liver disease (NAFLD) progression. In the present study, the investigators aimed to investigate the value of cardiovascular risk ratios of triglycerides, cholesterol, and lipoproteins as predictors of nonalcoholic steatohepatitis (NASH) and the correlation of such ratios with disease severity. PATIENTS AND METHODS: This study included 131 overweight and obese patients with NAFLD who were divided into NASH, borderline NASH, and non-NASH fatty liver (NNFL) subgroups according to NAFLD activity score (NAS) in liver biopsy, and 60 healthy participants as a control group. Lipid profile and lipid ratios including triglycerides/HDL (TGs/HDL), low-density lipoprotein/high-density lipoprotein (LDL/HDL) and total cholesterol/HDL (TC/HDL) ratios were measured. RESULTS: Significantly higher triglycerides/HDL ratio was found in NASH and borderline NASH, while higher cholesterol/HDL ratio was found in borderline NASH in comparison to controls. There were positive correlations between TGs/HDL and steatosis, ballooning, inflammation, BMI, and NAS; between LDL/HDL and inflammation; and between cholesterol/HDL and BMI, steatosis, and NAS. The highest AUC was that of TG/HDL (0.744), at a cut-off point of 3, with 71.8% sensitivity and 76.8% specificity. CONCLUSION: Triglycerides, cholesterol and lipoprotein ratios showed higher levels in NASH and correlated with NAFLD severity, and above these cut-off ratios, we can rule in the NASH cases which confer also the cardiovascular morbidities. Structured lipid ratios could serve as markers to screen NASH progression from simple steatosis cases and clarify the link of NASH with the cardiovascular risk prediction in overweight and obese patients.

Abdominal subcutaneous fat thickness and homeostasis model assessment of insulin resistance as simple predictors of nonalcoholic steatohepatitis.

Background: Obesity, insulin resistance, and diabetes are major risk factors for nonalcoholic fatty liver disease (NAFLD). This study aims to evaluate the association between different grades of NAFLD and abdominal subcutaneous fat thickness with the homeostasis model assessment of insulin resistance (HOMA-IR). Methods: In this pilot study, 59 obese nondiabetic participants with NAFLD were enrolled. Total cholesterol, HbA1c, and HOMA-IR were measured. Abdominal subcutaneous fat thickness in the midline just below the xiphoid process in front of the left lobe of the liver (LSFT) and in the umbilical region (USFT), and the degree of hepatic steatosis, were evaluated by ultrasound scans, and their correlation with the degree of steatosis and the NAFLD Activity Score in liver biopsy was assessed. Results: Of the 59 studied participants, 15 had mild, 17 had moderate, and 27 had severe hepatic steatosis by abdominal ultrasound. The mean ± SD HOMA-IR level in NAFLD patients was 5.41±2.70. The severity of hepatic steatosis positively correlated with body mass index (P<0.001), HOMA-IR (P<0.001), serum triglycerides (P=0.001), LSFT (P<0.001), and USFT (P<0.001). Receiver operating characteristics analysis showed that LSFT at a cut-off of 3.45 cm is the most accurate predictor of severe hepatic steatosis, with 74.1% sensitivity and 84.4% specificity. The best cut-off of USFT for identifying severe hepatic steatosis is 4.55 cm, with 63% sensitivity and 81.3% specificity. Conclusion: Abdominal subcutaneous fat thicknesses in front of the left lobe of the liver and in the umbilical region, together with HOMA-IR, are reliable indicators of the severity of NAFLD in obese nondiabetic individuals.

Assessment of Quality of Life (QoL) in Systemic Lupus Erythematosus Patients at a Tertiary Care Hospital in Egypt.

Systemic Lupus Erythematosus (SLE) has a profound impact on quality of life. OBJECTIVE: The objective of this study was to explore the quality of life among Egyptian SLE patients and to assess its relationships with demographic and clinical features. METHODS: One hundred sixty-four SLE patients were recruited for this study. Demographic information; clinical parameters; disease activity, as evaluated by the systemic lupus erythematosus Disease Activity Index; and organ damage, as assessed by the systemic lupus international Collaborative Clinics/American College of Rheumatology Damage Index, were reported. Quality of life was assessed with a quality of life questionnaire specifically designed for patients with systemic lupus erythematosus; the questions are grouped in the following six domains: physical function, sociooccupational activities, symptoms, treatment, mood, and self-image. Higher values indicate poorer quality of life. RESULTS: Of the 164 Egyptian SLE patients who completed the survey, 142 (86.6%) were women. The mean age of the participants was 31± 8 years, the mean systemic lupus erythematosus disease activity index score was 17 ± 11, the mean systemic lupus international collaborative clinics/ American College of Rheumatology Damage Index score was 0.9 ± 1.2, and the mean quality of life score was 18.23± 6.89. Strong correlations were found between the total quality of life score and the scores for each domain of the questionnaire separately and disease activity, neurological manifestations, renal manifestations and musculoskeletal manifestations (p<0.0001); moreover, there was a significant positive correlation between the Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index score and the total quality of life score (p=0.005). CONCLUSION: Poor quality of life among Egyptian SLE patients and disease activity are strongly related to impaired lifestyles in these patients.