Association of rheumatological markers with neuronal antibodies, cerebrospinal fluid, electroencephalography, and magnetic resonance imaging findings in 224 patients with psychotic syndromes.

INTRODUCTION: Psychotic syndromes can have autoimmune-mediated causes in some patients. Thus, this retrospective work aims to investigate the role of rheumatological markers in the development of psychosis. PATIENTS AND METHODS: In total, 224 patients with psychotic syndromes receiving a "rheumatological laboratory screening" (including C-reactive protein [CRP], immunofixation, complement factors, rheumatoid factor [RF], antiphospholipid antibodies [APAs], antineutrophil cytoplasmic antibodies [ANCAs], and antinuclear antibodies [ANAs]) were analyzed. A further diagnostic work-up included investigations of neuronal antibodies and cerebrospinal fluid (CSF), as well as electroencephalography (EEG) and magnetic resonance imaging (MRI) of the brain. ANA testing was routinely performed in all patients using serum on human epithelioma-2 (Hep2) cells, and a subset of patients (N = 73) also underwent tissue-based assays from serum and CSF. The number of cases with autoimmune psychotic syndromes was descriptively collected, and ANA-positive and -negative patients were compared in detail. RESULTS: CRP was elevated in 9 % of patients, immunofixation identified alterations in 8 %, complement factor C3 was decreased in 14 %, RF was elevated in 1 %, APAs were elevated in 7 %, ANCAs were not clearly positive, and ANAs were positive in 19 % (extractable nuclear antigen [ENA] differentiation resulted in positive findings in 14 patients). From the 73 patient samples additionally investigated using tissue-based assays, there were 26 positive results for some kind of ANA (36 %), and overall using both methods, 54 patients (24 %) were considered positive for ANAs. A neuropsychiatric evaluation revealed a possible autoimmune psychotic syndrome in seven patients (3 %) and a probable autoimmune psychotic syndrome in two patients (1 %). ANA-positive patients were more frequently treated with antidepressants (p = 0.040) and had a higher number of somatic comorbidities (p < 0.001). In addition, (chronic) inflammatory MRI lesions (p = 0.008) and focal atrophies (p = 0.012) were found more frequently in ANA-positive than ANA-negative patients. DISCUSSION: Rheumatological screening led to suspicion of a possible or probable autoimmune psychotic syndrome in 4%. ANAs were associated with MRI pathologies. Therefore, rheumatological processes may contribute to the development of psychotic syndromes in rare cases.

Hepatic and Extrahepatic Characteristics of Autoimmune Hepatitis: A 23-year Hospital-Based Cohort Study.

BACKGROUND: The characteristics of autoimmune hepatitis (AIH) in Asia mostly remain elusive. METHODS: A cohort study of liver biopsy-proven AIH patients was conducted in a tertiary care cancer of Taiwan. RESULTS: From 1999 to 2022, of 13,766 patients who underwent liver biopsy, 150 patients with AIH were enrolled. The female-to-male ratio was 2.26. At baseline, the mean age was 51.09 years, mean alanine aminotransferase level was 494.11 U/L, and 17 (11.3%) had cirrhosis. All except one patient had AIH type 1. The females were older and had higher baseline cirrhosis rates than did the males. The 23-year cumulative incidences of cirrhosis, hepatocellular carcinoma (HCC), mortality/liver transplantation, autoimmune diseases and extrahepatic cancer were 64.2%, 13.3%, 23.4%, 30.7% and 21.2%, respectively. The 1-year, 2-year, 3-year, 5-year, 10-year and 20-year postimmunosuppressive therapy relapse rates were 60%, 78.2%, 81.8%, 89.1%, 94.5% and 100%, respectively. Baseline associations were as follows: alkaline phosphatase (Alk-p) levels with postimmunosuppressive therapy flare [hazard ratio (HR): 1.003; 95% CI HR: 1.000-1.005]; age with HCC (1.072; 1.010-1.138) and all-cause cancer (1.041;1.005-1.079); cirrhosis with mortality/liver transplantation (11.933;1.984-71.787); and antinuclear antibody (ANA) titers with mortality/liver transplantation (1.001;1.000-1.003), cirrhosis (1.001;1.000-1.002), and autoimmune diseases (1.001; 1.000-1.002). CONCLUSION: In an Asian country endemic for viral hepatitis, the female-to-male and baseline cirrhosis rates of AIH patients were lower than expected, while over 60% of the patients eventually developed cirrhosis. The high posttherapy relapse rate warrants cautious monitoring, particularly for patients with high baseline Alk-p levels. Baseline age, cirrhosis status and ANA titers are crucial for outcomes.

Chronic Adult-Onset Still's Disease With Positive Antinuclear Antibodies: Navigating Diagnostic Dilemmas and Clinical Implications.

Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory disorder characterized by fever, rash, and joint pain. Despite primarily affecting young adults, it can occur at any age, presenting diagnostic challenges due to its heterogeneous nature and lack of specific laboratory findings. The subset of AOSD with positive antinuclear antibody (ANA) adds complexity, potentially overlapping with other autoimmune conditions. We describe a case of a 30-year-old female with a two-year history of fever, weight loss, and joint pain, initially misdiagnosed as seronegative arthritis with hypothyroidism. Further evaluation revealed severe anemia, leucocytosis, and hepatosplenomegaly. Despite a strongly positive ANA, the absence of systemic lupus erythematosus (SLE) features led to a diagnosis of chronic AOSD. Treatment with steroids and disease-modifying antirheumatic drugs (DMARDs) resulted in clinical improvement, highlighting the importance of accurate disease classification for tailored management in ANA-positive AOSD. This case underscores the diagnostic challenges of AOSD and emphasizes the need for precise classification for optimal treatment strategies.

Major low-energy trauma results in non-specific immunoglobulin generation without evidence for specific autoantibody production: A prospective cohort study.

Cellular debris resulting from large trauma might overwhelm the scavenger mechanisms and lead to autoimmune reactions. We analysed whether a major well-defined trauma in humans induces laboratory signs of transient autoimmunity in the months after the insult. We included 50 patients with pertrochanteric femur fracture undergoing intramedullary nail osteosynthesis in a prospective cohort study and followed them at 3-4 days, 6 weeks, 12 weeks and 12 months postoperatively. By standard techniques, we assessed levels of total immunoglobulins, anti-nuclear antibodies (ANA), anti-cardiolipin antibodies, anti-dsDNA antibodies and anti-C1q antibodies, as well as antibodies against cytomegalovirus (CMV) as a control. Blood leukocyte differential and lymphocyte subpopulations were determined at baseline and in the first two postoperative samples. The mean age of the patients reached 80.1 years, and 23 (46%) completed all visits. Serum concentrations of total IgG, IgM and IgA increased at all follow-up time points. The ANA fluorescence light intensity units increased at 12 weeks and 12 months postoperatively (p < 0.0001), but the proportion of ANA-positive patients did not change (35%). The values of anti-C1q mildly increased at all follow-up visits, but not the ratio to total IgG. Anti-dsDNA remained negative in all patients, and anti-cardiolipin IgG/IgM antibodies did not change. Anti-CMV IgG antibodies increased significantly at all follow-up visits, without change in the ratio to total IgG. Flow cytometry showed an increased proportion of B-cells 3-4 days postoperatively. In conclusion, major musculoskeletal trauma in elderly patients induces a generalized non-specific increase in immunoglobulin production without laboratory signs for enhanced systemic autoimmunity.

The First Iranian Case of Unstable Hemoglobin Santa Ana.

In this report, we describe a 6-year-old girl with a medical history of pallor, mild icterus, anemia, blood transfusion and abnormal hemoglobin variant analysis on capillary electrophoresis. She was referred for further analysis. DNA sequencing of the proband revealed a de novo mutation in Codon 88 (CTG > CCG) of the ß-globin gene (HBB: c.266T > C) in a heterozygous state compatible with hemoglobin Santa Ana, an unstable hemoglobin. This is the first case of Hb Santa Ana from Iran associated with moderate to severe anemia who underwent splenectomy with clinical improvement.

Pulmonary Manifestations of Systemic Lupus Erythematosus Among Adults in Aseer Region, Saudi Arabia.

Background: Nearly half of the Systemic lupus erythematosus (SLE) patients develop lung involvement. The study assessed the extent of pulmonary involvement among SLE patients and to identify the associated factors in the population. Methodology: This retrospective cohort study was conducted at Aseer Hospital and Khamis Myshat Hospital in the Southern region of Saudi Arabia. The study spanned from January 1, 2016, to June 3, 2023. Patient inclusion criteria encompassed individuals who received a definitive diagnosis and classification as per American College of Rheumatology criteria, while patients under 18 years of age and those with mixed connective tissue diseases were exclude. Results: A total of 247 participants were included. 41.7% (n=103) aged 41 years and older, 95.1% (n = 235) were females. Around 10.10% had diabetes mellitus and 17.00% had hypertension and hypothyroidism. Lupus Nephritis was in 15.40%. Chest involvement was reported in 21.9%, in the form of pleuritis (6.10%), pleural effusion (4.00%), and lupus pneumonitis (4.00%), interstitial lung disease (4.00%), pulmonary embolism (3.60%) of individuals, and pulmonary hemorrhage (2.80%). The respiratory symptoms reported by SLE were; dyspnea, cough, and chest pain each having a prevalence of around 18.0%. Palpitations have a relatively high occurrence at 13.80%. Meanwhile, hemoptysis (blood coughing) has a lower prevalence of 1.20%, and fever is reported at 2.80%. Having chronic kidney disease and hypertension were significantly associated with having pulmonary involvement; (χ2=3.308, p=0.027) and (χ2=7.782, Fisher's p=0.002) respectively. The seropositivity for antiphospholipid Abs, anti-CCP, and antids-DNA were significantly associated with pulmonary involvement (χ2=3.239, =p=0.049), (χ2=4.621, Fisher's p=0.023), and (χ2=8.248, p=0.010) respectively. Conclusion: The study found that 21.9% of SLE patients experience chest involvement, with varying degrees of pulmonary symptoms. Factors such as chronic kidney disease, hypertension, antiphospholipid antibodies, Anti-CCP positivity, and seropositivity for Anti-dsDNA were found to be significant associations with lung involvement, contributing to our understanding of SLE.

Long-term follow-up of 109 children with juvenile idiopathic oligoarthritis after first intra-articular corticosteroid injection.

BACKGROUND: To evaluate long-term outcomes and prognostic factors in patients with juvenile idiopathic arthritis (JIA), presenting as oligoarthritis, who received IAC as the first treatment for their disease. METHODS: We conducted retrospective study at the University Children's Hospital Ljubljana, Slovenia, from January 2015 to May 2023 in children with JIA, clinically presenting as oligoarthritis receiving intra-articular corticosteroid injection (IAC) as the initial treatment. Patient and treatment data were collected, and the outcomes were categorized into three groups based on the later need for therapy: no therapy needed, only additional IAC needed and systemic therapy needed. The last group was further divided based on the requirement of bDMARD. Log-rank (Mantel-Cox) survival analyses compared different outcome groups. RESULTS: We included 109 patients with JIA, presenting as oligoarthritis (63% female), who were first treated with IAC. The mean age at IAC was 8.0 years, with a 4.3-year follow-up. Notably, 38.5% of patients did not require additional therapy post-IAC, whereas 15.5% required only additional IAC. Systemic therapy, mainly methotrexate (MTX), was necessary for 45.9% of patients, initiated in average 7.8 months post-IAC. Biologic therapy was initiated in 22% in average 2.2 years post-IAC. Number of injected joints correlated with the need for biologics. At the last follow-up, 88.9% had inactive disease. ANA positivity (P = 0.049, chi square 3.89) and HLA B27 antigen presence (P = 0.050, chi square 3.85) were associated with the need for systemic therapy. A subgroup of children older than 8 years, ANA and HLA B27 negative required significantly less systemic (25.8%) and biologic therapy (9.6%) compared to other patients (p = 0.050, chi square 3.77). CONCLUSION: Almost 40% of children with oligoarticular JIA requiring IAC did not progress to chronic disease. Younger age, ANA positivity, and HLA B27 presence were predictive factors for systemic therapy, while the number of injected joints predicted the future need for biologic therapy.

High Doses of ANA12 Improve Phenobarbital Efficacy in a Model of Neonatal Post-Ischemic Seizures.

Phenobarbital (PB) remains the first-line medication for neonatal seizures. Yet, seizures in many newborns, particularly those associated with perinatal ischemia, are resistant to PB. Previous animal studies have shown that in postnatal day P7 mice pups with ischemic stroke induced by unilateral carotid ligation, the tyrosine receptor kinase B (TrkB) antagonist ANA12 (N-[2-[[(hexahydro-2-oxo-1H-azepin-3-yl)amino]carbonyl]phenyl]-benzo[b]thiophene-2-carboxamide, 5 mg/kg) improved the efficacy of PB in reducing seizure occurrence. To meet optimal standards of effectiveness, a wider range of ANA12 doses must be tested. Here, using the unilateral carotid ligation model, we tested the effectiveness of higher doses of ANA12 (10 and 20 mg/kg) on the ability of PB to reduce seizure burden, ameliorate cell death (assessed by Fluoro-Jade staining), and affect neurodevelopment (righting reflex, negative geotaxis test, open field test). We found that a single dose of ANA12 (10 or 20 mg/kg) given 1 h after unilateral carotid ligation in P7 pups reduced seizure burden and neocortical and striatal neuron death without impairing developmental reflexes. In conclusion, ANA12 at a range of doses (10-20 mg/kg) enhanced PB effectiveness for the treatment of perinatal ischemia-related seizures, suggesting that this agent might be a clinically safe and effective adjunctive agent for the treatment of pharmacoresistant neonatal seizures.

Excellent response to treatment with hydroxychloroquine in pediatric patients with SLE-related immune thrombocytopenia.

BACKGROUND: Pediatric immune thrombocytopenia (ITP) may precede systemic autoimmune disorders. In adolescent patients with ITP, routine screening for systemic lupus erythematosus (SLE) may be performed by testing for antinuclear antibody (ANA) titer. Hydroxychloroquine (HCQ) is a safe and effective immunomodulatory drug in patients with SLE but rarely used in ITP. We analyzed the platelet count response and safety of HCQ in treating pediatric patients with SLE-related ITP. METHODS: A retrospective study including pediatric patients with ITP and definite or incomplete SLE, who were treated with HCQ during 2010-2021. SLE was defined by ANA titer ≥ 1:160 as measured by immunofluorescence and ≥10 points according to the 2019 EULAR/ACR 2019 classification criteria, while patients with incomplete SLE achieved a score < 10. Complete response (CR) of the platelet count was defined as platelet count > 100 × 109/L; partial response (PR) as platelet count 30-100 × 109/L and exceeding ≥ twice baseline counts. RESULTS: Of the 17 patients included (median age 15.5 years; IQR 3.6), 15 (88.2%) were female, 13 had definite SLE, and four had incomplete SLE. HCQ was initiated at a median of 17 months after ITP diagnosis with a median platelet count of 38 × 109/L (IQR 28). At 8 weeks, 8 (47.1%) patients responded, including 6 (35.3%) achieving CR. After one year, the overall response was 82.4%, with the remaining patients having stable platelet counts requiring no additional ITP therapy. The response was maintained at a median follow-up of 42 months. No adverse effects to HCQ were noted. CONCLUSION: Pediatric patients with SLE-related ITP may benefit from treatment with HCQ.

Validation of the NUT CRACKER Diagnostic Algorithm and Prediction for Cashew and Pistachio Co-Allergy.

BACKGROUND: Because of the high cross-sensitization among tree nuts, the NUT CRACKER (Nut Co-reactivity-Acquiring Knowledge for Elimination Recommendations) study proposed a diagnostic algorithm to minimize the number of required oral food challenges (OFCs). OBJECTIVE: To validate the algorithm for cashew and pistachio allergy and determine markers for allergic severity. METHODS: Patients (n = 125) with a median age of 7.8 (interquartile range, 5.9-11.2) years with suspected tree nut allergy were evaluated prospectively with decision tree points on the basis of skin prick test (SPT), basophil activation test (BAT), and knowledge of the coincidence of allergies. Validation of allergic status was determined by OFC. Markers of clinical severity were evaluated using the combined original and prospective cohort (n = 187) in relationship to SPT, BAT, and Ana o 3-sIgE. RESULTS: Reactivity to cashew in SPT, BAT, and Ana o 3-sIgE and the incidence of abdominal pain on challenge were significantly higher in dual-allergic cashew/pistachio patients (n = 82) versus single cashew allergic patients (n = 18) (P = .001). All 3 diagnostic tests showed significant inverse correlation with log10 reaction doses for positive cashew OFC. The algorithm reduced overall the total number of OFCs by 72.0%, with a positive predictive value and negative predictive value of 93.0% and 99.0%, respectively. Cashew false-positives were observed primarily in hazelnut-allergic patients (P = .026). In this population, Ana o 3-specific IgE could diagnose cashew allergy with a sensitivity of more than 90% and a specificity of more than 95%. CONCLUSIONS: The NUT CRACKER diagnostic algorithm was validated and reduced the number of diagnostic OFCs required. Markers for severity phenotypes may guide oral immunotherapy protocols, improving the risk/benefit ratio for patients.

[Soft and hard tissue changes of hyperdivergent class â ¡ patients before and after orthodontic extraction treatment].

OBJECTIVE: To investigate the hard and soft tissue changing trend and contributing factors of skeletal class Ⅱ hyperdivergent patients before and after orthodontic camouflage treatment by analyzing the cephalogram and the three dimensional (3D) facial scan data. METHODS: Eighteen skeletal class Ⅱ hyperdivergent adult female patients who finished camouflage orthodontic treatment were selected. Skeletal and dental measurements were carried out with the cephalometric analysis before and after the treatment. 3D facial data before and after orthodontic treatment were acquired and the anatomical landmarks were set after the repositioning and superimposition process. Hard tissue measurement included 17 mea-surement indicators (sella-nasion-subspinale angle, sella-nasion-supramental angle, subspinale-nasion-supramental angle, facial angle, angle of convexity, Frankfort horizontal plane-mandibular plane angle (FH-MP), Y axis angle, sella-nasion plane-mandibular plane angle (MP-SN), pogonion-nasion-supramental distance, upper incisor-nasion-subspinale distance, upper incisor to sella-nasion, lower incisor-nasion-supramental distance, lower incisor-nasion-supramental angle, upper incisor to lower incisor, upper incisor to sella-nasion, lower incisor-mandibular plane angle, and Z angle), and the changes before and after treatment were measured for 11 of them. Twenty soft tissue landmarks (left/right cheekbone, left/right chelion, left/right crista philtra, soft tissue gnathion, left/right gonion, glabella, labrale infe-rius, labrale superius, soft tissue menton, left/right mid-mandibular border, soft tissue pogonion, stomion superius, sublabial, subnasale, and supralabial) and 9 soft tissue indicators (lower lip height, facial convexity, lower vermilion height, mandibular contour, nasolabial angle, philtral length, philtral width, upper lip height, and upper vermilion height) were measured and recorded for treatment changes. Linear-regression analysis and correlation analysis were carried out for analyzing the relationship between hard and soft tissue changes before and after the treatment. RESULTS: Significant differences were noticed for 18 out of the 20 cephalometric measurements and facial measurements before and after the treatment (P < 0.05), which mainly represented the sagittal retraction of lip area after the treatment. Significant vertical displacements were revealed for soft tissue menton after treatment [(1.88±2.61) mm, P < 0.05]. Significant sagittal displacements were revealed for left/right cheilion [(-2.95±1.9) mm, (-2.90±1.92) mm], labrale inferius[(-4.94±1.95) mm], labrale superius[(-3.25±1.44) mm], sublabial [(-3.10±3.5) mm], and subnasale [(-1.23±1.06) mm] after treatment (P < 0.05). An average of 4.10°±2.57° increasement was noticed for Z angle after treatment. High correlation (r>0.7) was noticed for the displacement of menton after treatment with FH-MP, with the rate of -0.183 :1, and MP-SN, with the rate of -0.157 :1. Moderate correlations (0.7≥r>0.4) were noticed for the other measurements with correlations (P < 0.05). CONCLUSION: A certain extent of facial improvements could be achieved with orthodontic camouflage treatment for skeletal class Ⅱ hyperdivergent patients, which were mostly represented by the improvement of sagittal relationship of nose, lips, and chin. Certain correlations were noticed for the hard and soft tissue changes.

Retrospective, single-center analysis of autoimmune hepatitis in Jordanian children: clinical features, treatments, and outcomes.

OBJECTIVES: This study describes clinical, biochemical, and histological features and long-term outcomes in pediatric patients diagnosed with autoimmune hepatitis (AIH) at King Abdullah University Hospital, Jordan. DESIGN: Retrospective, single-center study. SETTING: King Abdullah University Hospital, Jordan. PARTICIPANTS: Inclusion of all pediatric patients with AIH diagnosed at our hospital from 2015 to 2023. Exclusion criteria was patients aged over 18 at time of diagnosis and those diagnosed elsewhere. OUTCOME MEASURES: Understanding clinical, biochemical, and histological AIH features in children, evaluating treatment responses, and reporting short- and long-term complications, including mortality. RESULTS: Sixteen pediatric cases were diagnosed, with an average age of 9.84 ± 4.13 years. Females comprised 75% of patients, and 31.3% presented with acute liver failure. Jaundice was the most common symptom, and hepatosplenomegaly was observed in 18% of cases. Most patients had elevated transaminase levels, along with positive anti-smooth muscle antibody (ASMA) and antinuclear antibodies (ANA). Common hematological abnormalities included anemia (56.3%) and thrombocytopenia (37.5%). All patients underwent liver biopsy, with interface hepatitis present in 81.3% of cases. Treatment mainly involved prednisone and azathioprine. Three patients died, one discontinued therapy, two patients were lost to follow-up, and 10 remained on treatment. CONCLUSION: Autoimmune hepatitis affects Jordanian children, primarily female children. Jaundice is the most common presenting symptoms. Only Type I AIH occurred in our cohort. Although of good response to conventional treatment with steroids and immunosuppression, mortality reached 18.8%.

Frequency of Repeating Antinuclear Antibody Testing: When Less Is More.

Objectives Antinuclear antibodies (ANA) are autoantibodies that are associated with and ordered to diagnose autoimmune connective tissue disease. ANA have high sensitivity (~98%) but low specificity (~75%), and because they can be found in healthy individuals and non-rheumatologic conditions leading to their elevation, ANA tests are often requested and interpreted inappropriately by clinicians. The aim of this study was to retrospectively assess how frequently ANA testing is repeated in the adult population of Saudi Arabia (SA) and which factors are associated with and lead to inappropriate testing. Methodology We investigated a study group of 40,634 adult patients who underwent 229,825 ANA tests from 2018 to 2022 in an academic hospital in Jeddah, SA. We took a random sample of 500 patients from the study group, along with their 998 ANA tests, to look in depth into our research questions. Variables related to patients, ANA tests, and ordering physicians were collected. Descriptive and analytical statistics were employed to address the research questions, and a p-value < 0.05 was considered statistically significant. Results We found 57% of the ordered ANA tests to have positive results, with the most common titers of mild positivity being 1:80 and 1:160. Most repeated ANA tests were ordered with an interval of more than one year, and when repeated, 67% of test results remained unchanged. The majority of seroconversions resulted from negative ANA tests or those with weak (titer 1:40) or mild positivity (titer 1:80-1:160). The results of the moderate (titer 1:320-1:640) and strong (titer ≥1280) positivity ANA tests did not change. Only 11% of repeated ANA tests were found to be appropriate for repetition. The most common specialties associated with ordering ANA tests in general were internal medicine, followed by rheumatology, and finally family medicine. Our correlation analysis revealed that being female, having systemic connective tissue disease, and having a rheumatologist as a specialist were all associated with ordering more than 10 ANA tests (p < 0.05). Conclusion Because the results of repeated ANA tests did not change much, our study suggests that the cost of repeating ANA tests and the subsequent potentially unnecessary interventions should all be carefully examined before scheduling a repeated ANA test. Further studies involving patients from SA and across wider healthcare settings (academic, community, and private hospitals and healthcare centers) are warranted.

Clinical patterns of disease: From early systemic lupus erythematosus to late-onset disease.

Systemic lupus erythematosus (SLE) is a complex disease with an insidious clinical presentation. In up to half of the cases, SLE onset is characterized by clinical and serological manifestations that, although specific, are insufficient to fulfill the classification criteria. This condition, called incomplete SLE, could be as challenging as the definite and classifiable SLE and requires to be treated according to the severity of clinical manifestations. In addition, an early SLE diagnosis and therapeutic intervention can positively influence the disease outcome, including remission rate and damage accrual. After diagnosis, the disease course is relapsing-remitting for most patients. Time in remission and cumulative glucocorticoid exposure are the most important factors for prognosis. Therefore, timely identification of SLE clinical patterns may help tailor the therapeutic intervention to the disease course. Late-onset SLE is rare but more often associated with delayed diagnosis and a higher incidence of comorbidities, including Sjogren's syndrome. This review focuses on the SLE disease course, providing actionable strategies for early diagnosis, an overview of the possible clinical patterns of SLE, and the clinical variation associated with the different age-at-onset SLE groups.

Comparison of Two Dexmedetomidine Administration Strategies on the Incidence of Postoperative Respiratory Complications: A Retrospective, Inverse Probability of Treatment Weighted Study.

Randomized controlled trials have shown a higher risk of postoperative hypoxemia and delayed extubation with opioid-free anesthesia (OFA), compared with opioid anesthesia. The practice of OFA is not standardized. The objective of this study is to investigate the association between the dexmedetomidine administration protocol used and the occurrence of postoperative respiratory complications. This work is a retrospective, propensity score-adjusted study (inverse probability of treatment weighting) conducted between January 2019 and September 2021 in a French tertiary care university hospital, including 180 adult patients undergoing major digestive surgery. Comparison of 2 anesthesia protocols: with a continuous intravenous maintenance dose of dexmedetomidine following a bolus (group B+M, n = 105) or with a bolus dose alone (group B, n = 75). The main outcome measure was a composite respiratory end point within 24 hours of surgery. There was no significant difference in the incidence of overall respiratory complications, as assessed by the primary end point. Nevertheless, there were more patients with postoperative hypercapnia in group B+M than in group B (16% vs 2.5%, P = .004). Patients in group B+M were extubated later than patients in group B (group B+M, median 40 minutes, IQR 20-74 minutes; group B, median 20 minutes, IQR 10-50 minutes; P = .004). Our study showed negative results for the primary end point. However, data on the increased risk of postoperative hypercapnia in patients receiving a maintenance dose of dexmedetomidine are new. Other prospective randomized studies with greater power are necessary to confirm these data and to make OFA safer, by reducing the prescribed doses of dexmedetomidine.

A novel way to evaluate autoantibody interference in samples with mixed antinuclear antibody patterns in the HEp-2 cell based indirect immunofluorescence assay and comparison of conventional microscopic and computer-aided pattern recognition.

BACKGROUND: A major challenge of the HEp-2 cell-based indirect immunofluorescence (IIF) assays is the correct identification of the individual anti-nuclear antibodies (ANAs) if more than one is present in a sample. We created artificial mixes by pooling two different samples with a single autoantibody in different titers. Comparison of the expected and observed patterns and titers clarifies the interference between the two tested ANAs. METHODS: Serum samples with a single homogeneous or speckled ANA pattern were serially diluted and mixed in 16 combinations, providing end-point titers of 1:5,120 to 1:80 for both patterns. These mixes were tested by a HEp-2 IIF assay and were evaluated by conventional evaluation, the EUROPattern (EPa) system and on-screen analysis. RESULTS: Homogeneous pattern can alter the identification of the speckled pattern much more than vice versa, but both has an interfering effect on the other. The effect of the interfering on the tested pattern was higher if the titer of the former one was higher. The pattern recognition efficacy of conventional and the on-screen evaluation was similar and superior compared to the EPa analysis. CONCLUSIONS: The application of artificial mixed samples can help the evaluation of the efficacy of manual and computer-aided ANA HEp-2 pattern recognition.

Effect of serum autoantibodies on the COVID-19 patient's prognosis.

Objectives: Virus infection closely associated with autoimmune disease. The study aimed to explore the autoantibody profiles and the correlation of autoantibodies with the disease severity and the prognosis of the coronavirus disease 2019 (COVID-19) patients. Methods: Three hundred thirty-seven hospitalized COVID-19 patients from 6th to 23rd January 2023 were enrolled. Logistic and Cox regression analyses were used to analyze the risk factors for the patient's disease severity and outcome. The association between Anti-extractable nuclear antigen antibody (ENA) positivity and the prognosis of COVID-19 patients was analyzed using Kaplan-Meier survival curves. Results: 137 of COVID-19 patients were detected positive for antinuclear antibody (ANA), 61 had positive results for ENA, and 38 were positive for ANA and ENA. ANA positivity rate was higher in non-severe illness group (p = 0.032). COVID-19 patients who died during hospitalization had a high rate of ENA positivity than convalescent patients (p = 0.002). Multivariate logistic regression showed that ANA positivity was a protective factor for the disease severity of COVID-19. Multivariate Cox regression analysis revealed that ENA positivity, white blood cells count (WBC), aspartate aminotransferase (AST), Creatinine (CREA), and CRP were independent risk factors for the outcome of COVID-19 patients, and that COVID-19 patients with ENA positivity had a lower cumulative survival rate (p = 0.002). Conclusion: A spectrum of autoantibodies were expressed in COVID-19 patients, among which ANA and ENA positivity was associated with the severity and prognosis of COVID-19. Therefore, autoantibodies may help to assess the disease severity and prognosis of COVID-19 patients.

Pediatric Lupus Retinopathy: A Rare Manifestation of a Grave Systemic Disorder.

We describe a rare case of pediatric systemic lupus erythematosus (pSLE) and its successful management. A nine-year-old female presented with bilateral diminution of vision, fever, and rash in the malar region, chest, abdomen, back, and arms for three months. Clinical examination and multimodal imaging revealed bilateral extensive retinal vasculitis with macular edema. Laboratory investigations revealed anemia, leucopenia, positive serum antinuclear antibody (ANA), and anti-extractable nuclear antigen (ENA) antibodies. A diagnosis of pediatric lupus retinopathy was made. Ocular and systemic manifestations responded well to intense systemic immunosuppression (pulse intravenous {IV} methylprednisolone, oral prednisolone and hydroxychloroquine {HCQ}, six cycles of IV cyclophosphamide, and oral azathioprine) along with topical steroids and laser photocoagulation, over the next 10 months. Though ocular manifestations are not a part of the diagnostic criteria for SLE, they may be markers of active systemic disease. Ophthalmologists and rheumatologists must treat this complex disease in tandem in order to provide optimum patient care.

ANA-negative severe lupus-like presentation: Is it lupus or not?

Key Clinical Message: Systemic lupus erythematosus is difficult to diagnose in patients who are antinuclear antibody (ANA) negative and lack typical clinical manifestations. For such patient who presented ANA-negative severe lupus-like manifestations, the diagnosis and treatment are a huge challenge. Histological findings may provide clues to diagnosis. Abstract: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by formation of autoantibodies to nuclear and cytoplasmic antigens. It was reported that a small subset of patients had typical clinical features of SLE with consistently negative antinuclear antibody (ANA), but such disease is usually mild and rarely involves multisystem. At present, there are no reports about severe lupus with ANA continued negative. Our report describes a 34-year-old Chinese woman who presented renal failure, multiple serous cavity effusion, and epilepsy, without malar rash, photosensitivity, lymphopenia, and arthritis. Further renal biopsy pathology revealed lupus-like nephritis. Autoantibodies, including ANA, antibodies against Smith and against double stranded DNA, were negative. Such a ANA negative and lack of typical clinical symptoms of SLE patient, but with severe lupus-like manifestations, whether it was lupus or not is worth discussing.

Discriminating between Homogeneous (AC-1) and Dense Fine Speckled (AC-2) Antinuclear Antibody Patterns: Re-Evaluation of Immunofluorescence Imaging.

Antinuclear antibodies (ANAs) are essential diagnostic markers in systemic autoimmune rheumatic diseases. Among the 30 ANA patterns, homogeneous (AC-1) and dense fine speckled (AC-2) should be focused on owing to their somewhat indistinct presentation in immunofluorescence imaging and distinct correlation with clinical conditions. This study aimed to develop a flowchart to guide discrimination between AC-1 and AC-2 patterns and to re-evaluate ANA samples according to this flowchart to verify its detection ability. We re-evaluated immunofluorescence imaging of 62 ANA blood samples simultaneously subjected to solid-phase assays for autoantibodies against dsDNA, nucleosomes, histones, and DFS70. The results showed statistically significant odd ratios (ORs) of detection of anti-DFS70 using AC-2 after re-evaluation of total samples (OR 101.9, 95% CI 11.7-886.4, p-value < 0.001) and subgroup analysis of patients' samples (OR 53.8, 95% CI 5.9-493.6, p-value < 0.001). The OR of anti-nucleosome/histone/dsDNA detection using AC-1 in re-evaluated data increased to 5.43 (95% CI 1.00-29.61, p-value = 0.05). In the analysis of specific autoantibodies, more than half of the samples with an AC-2 pattern (54.2%) had specific autoantibodies other than anti-DFS70. We conclude that the flowchart for discriminating between AC-1 and AC-2 ANA patterns in this study is a viable practical guide for other laboratories when encountering equivocal ANA results.