IFN-γ, IL-17A, IL-4, and IL-13: Potential Biomarkers for Prediction of the Effectiveness of Biologics in Psoriasis Patients.

Biologics are widely used to treat moderate-to-severe psoriasis. However, we have unmet needs for predicting individual patient responses to biologics before starting psoriasis treatment. We investigate a reliable platform and biomarkers for predicting individual patient responses to biologics. In a cohort study between 2018 and 2023 from a referral center in Taiwan, twenty psoriasis patients with or without psoriatic arthritis who had ever experienced two or more biologics were enrolled. Peripheral blood mononuclear cells obtained from these patients were treated with Streptococcus pyogenes and different biologics. The PASI reduction rate was strongly correlated with the reduction rate in the IL-13 level (p = 0.001) and the ratios of IFN-γ to IL-13 (p < 0.001), IFN-γ to IL-4 (p = 0.019), and IL-17A to IL-13 (p = 0.001). The PASI reduction difference was strongly correlated with the difference in the IFN-γ level (p = 0.002), the difference in the ratios of IFN-γ to IL-4 (p = 0.041), the difference in the ratios of IFN-γ to IL-13 (p = 0.006), the difference in the ratios of IL-17A to IL-4 (p = 0.011), and the difference in the ratios of IL-17A to IL-13 (p = 0.029). The biomarkers IFN-γ, IL-13, IFN-γ/IL4, IFN-γ/IL13, IL-17A/IL-4, and IL-17A/IL-13 are representative of the effectiveness of psoriasis treatment.

Ultrafast Doppler Imaging for Early Detection of Synovitis in Rheumatoid Arthritis.

OBJECTIVE: Current medical ultrasound systems possess limited sensitivity in detecting slow and weak blood flow during the early stages of rheumatoid arthritis (RA), leading to potential misdiagnosis. Ultrafast Doppler is capable of detecting slow and weak flow. This study was aimed at evaluating the diagnostic value of ultrafast Doppler for RA. METHODS: Thirty-three RA patients (19 established, 14 early stage) and 15 healthy participants were enrolled. A programmable imaging platform with ultrafast Doppler capability was used. The benchmark was a clinical system with conventional Doppler imaging. Standardized dorsal long-axis scanning of both wrists was performed. Both ultrafast and conventional power Doppler (PD) images were quantitatively analyzed with computer assistance and semiquantitatively scored with the Outcome Measures in Rheumatology (OMERACT) scoring system. RESULTS: Ultrafast PD revealed more blood area than conventional PD in both RA wrists and healthy wrists. Ultrafast PD OMERACT was positive in 65 of 66 RA wrists and 26 of 30 healthy wrists (sensitivity [SEN] = 0.985, accuracy [ACC] = 0.719), while conventional PD OMERACT was positive in 28 of 66 RA wrists and 0 of 30 healthy wrists (SEN = 0.424, ACC = 0.604). Ultrafast PD revealed a higher synovial PD area, dilated vessels and PD brightness in RA wrists. Peak synovial PD brightness had the best diagnostic value for RA (area under the receiver operating characteristic curve = 0.802, SEN = 0.909, ACC = 0.813). For early-stage RA patients, ultrafast peak synovial PD brightness had higher sensitivity and accuracy than conventional PD indexes. CONCLUSION: Ultrafast PD had an increase of 0.561 in sensitivity and 0.209 in accuracy when compared with conventional PD. With its high sensitivity, ultrafast PD can detect early synovitis and identify RA patients during the early phase.

The diagnostic and prognostic value of a line immunoblot assay in Taiwanese patients with systemic sclerosis.

BACKGROUND AND AIMS: We aimed to evaluate the diagnostic performance and prognostic value of disease-specific antibodies and anti-Ro52 using a commercial line immunoblot assay (LIA) in Taiwanese patients with systemic sclerosis (SSc). MATERIALS AND METHODS: We retrospectively enrolledall individuals at the Taichung Veterans General Hospital. We evaluated the diagnostic performance of LIA, anti-nuclear antibody (ANA) by indirect immunofluorescence (IIF) and also the association between the autoantibodies and the clinical phenotype using multivariable logistic regression. RESULTS: The LIA exhibited a sensitivity of 65.4% and a specificity of 65.4%, at the optimal cutoff values of 2 + signal intensity. By taking the result of ANA into consideration, the optimal cutoff point was redefined as 1+. We observed a higher risk of diffuse cutaneous SSc (dcSSc) in those with negative autoantibodies, positive anti-Scl-70, anti-RNA polymerase III, and anti-Ro-52. Interstitial lung disease (ILD) was associated with negative autoantibodies, as well as positive anti-Scl-70 and anti-Ro52. Anti-Ro52 positivity was also associated with pulmonary arterial hypertension (PAH) and gastrointestinal tract involvement. CONCLUSION: The presence of anti-Ro52 or the absence of SSc-specific autoantibodies may potentially indicate advanced diseases in patients with SSc. The incorporation of both IIF and LIA testing may improve the diagnostic specificity of SSc.

Deep learning-based assessment of knee septic arthritis using transformer features in sonographic modalities.

PURPOSE: Septic arthritis is an infectious disease. Conventionally, the diagnosis of septic arthritis can only be based on the identification of causal pathogens taken from synovial fluid, synovium or blood samples. However, the cultures require several days for the isolation of pathogens. A rapid assessment performed through computer-aided diagnosis (CAD) would bring timely treatment. METHODS: A total of 214 non-septic arthritis and 64 septic arthritis images generated by gray-scale (GS) and Power Doppler (PD) ultrasound modalities were collected for the experiment. A deep learning-based vision transformer (ViT) with pre-trained parameters were used for image feature extraction. The extracted features were then combined in machine learning classifiers with ten-fold cross validation in order to evaluate the abilities of septic arthritis classification. RESULTS: Using a support vector machine, GS and PD features can achieve an accuracy rate of 86% and 91%, with the area under the receiver operating characteristic curves (AUCs) being 0.90 and 0.92, respectively. The best accuracy (92%) and best AUC (0.92) was obtained by combining both feature sets. CONCLUSIONS: This is the first CAD system based on a deep learning approach for the diagnosis of septic arthritis as seen on knee ultrasound images. Using pre-trained ViT, both the accuracy and computation costs improved more than they had through convolutional neural networks. Additionally, automatically combining GS and PD generates a higher accuracy to better assist the physician's observations, thus providing a timely evaluation of septic arthritis.

The role of ultrasound synovitis scores for patients who are at risk of rheumatoid arthritis.

OBJECTIVES: The development of rheumatoid arthritis (RA) has been classified into 6 phases A-F according to the present risk factors in sequence of genes, environments, autoimmunity, arthralgia and joint swelling. To clarify the ultrasound synovitis scores in at-risk patients (phases C-E) and RA (phase F). METHODS: Patients who had been experiencing hand joint symptoms for at least 6 weeks and asymptomatic patients with positive rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies were enrolled. A 40-joint ultrasonography with semiquantitative synovitis scoring for gray scale (GS) and power Doppler (PD) images was performed. RESULTS: A total of 139 patients were enrolled and classified into non-RA, phase C, phase D, phase E and phase F. Total GS scores in phases C (17.4 ± 7.0), D (16.0 ± 5.4), E (18.5 ± 7.7) and F (21.8 ± 9.1) were higher than those in non-RA (9.8 ± 4.0, P < 0.001). The total PD score in phase F (3.1 ± 4.6) was higher than that in phases C (0.2 ± 0.5), D (0.1 ± 0.4), and E (0.1 ± 0.3), as well as in non-RA (0.0 ± 0.0, P < 0.01). A total GS score ≥14 differentiated patients at risk for RA from patients with non-RA (area under curve [AUC] 0.82), while a total PD score ≥2 differentiated patients with RA from patients at risk for RA (AUC 0.71). CONCLUSION: Total GS score may differentiate patients at risk for RA from non-RA patients, while total PD score may differentiate patients with RA from those who are at risk for RA.

Clinical predictors of early surgical intervention in patients with venomous snakebites.

BACKGROUND: Venomous snakebites induce tissue destruction and secondary infection; however, the optimal timing of surgical intervention for these complications remains unknown. This study assessed the clinical predictors of early surgical intervention in patients with snakebites. METHODS: This retrospective study included 63 patients (45 men and 18 women) with venomous snakebites. In addition to the snake species, the demographics, affected body parts, clinical characteristics, and ultrasound findings of the patients in the surgical (32 patients) and nonsurgical (31 patients) groups were analyzed and compared. RESULTS: A higher incidence of acute compartment syndrome, local ecchymosis, skin necrosis, bullae, blisters, and fever was found in the surgical group than in the nonsurgical group, and ultrasound findings of the absence of Doppler flow were more frequently noted in the surgical group than in the nonsurgical group. After adjustment using a multivariate logistic regression model, only advanced age, Naja atra bite, local ecchymosis, and bulla or blister formation remained significant factors for surgical intervention. Furthermore, comparison of the outcomes of patients who received early (≤ 24 h) and late (> 24 h) surgical intervention revealed that the duration of continuous negative pressure wound therapy (6 vs. 15 days; P = 0.006), duration of hospital stay (13 vs. 26 days; P = 0.002), and duration of outpatient follow-up (15 vs. 36 days; P < 0.001) were significantly lower in patients who received early surgical intervention. The final reconstructive surgery was simple among the patients who received surgical intervention within 24 h of being bitten (P = 0.028). CONCLUSION: In patients with snakebites, advanced age, high-risk clinical manifestations (e.g., local ecchymosis and bulla or blister formation), and Naja atra envenomation are predictors of surgical intervention within 24 h.

The electronic medical record management systems may improve monitoring and control of disease activity in patients with ankylosing spondylitis.

To investigate the impact of an electronic medical record management system (EMRMS) on disease activity and the frequency of outpatient visits among patients with ankylosing spondylitis (AS). We identified 652 patients with AS who were followed up for at least 1 year before and after the first Ankylosing Spondylitis Disease Activity Score (ASDAS) assessment and compared the number of outpatient visits and average visit time within 1 year before and after the initial ASDAS assessment. Finally, we analyzed 201 patients with AS who had complete data and received ≥ 3 continuous ASDAS assessments at an interval of 3 months, and we compared the results of the second and third ASDAS assessments with those of the first. The number of annual outpatient visits increased after ASDAS assessment (4.0 (4.0, 7.0) vs. 4.0 (4.0, 8.0), p < 0.001), particularly among those with a high initial disease activity. The average visit time was reduced within 1 year after ASDAS assessment (6.4 (8.5, 11.2) vs. 6.3 (8.3, 10.8) min, p = 0.073), especially among patients whose with an inactive disease activity was < 1.3 (ASDAS C-reactive protein (CRP) 6.7 (8.8, 11.1) vs. 6.1 (8.0, 10.3) min, p = 0.033; ASDAS erythrocyte sedimentation rate (ESR) 6.4 (8.7, 11.1) vs. 6.1 (8.1, 10.0) min, p = 0.027). Among patients who received at least three ASDAS assessments, the third ASDAS-CRP tended to be lower than the first (1.5 (0.9, 2.1) vs. 1.4 (0.8, 1.9), p = 0.058). The use of an EMRMS increased the frequency of ambulatory visits among AS patients with high and very high disease activity and reduced the visit time among those with an inactive disease. Continual ASDAS assessments may help control the disease activity of patients with AS.

Cortical thickness and diffusion tensor imaging in patients with neuropsychiatric systemic lupus erythematosus, with normal structure on brain MRI.

OBJECTIVES: Neuropsychiatric systemic lupus erythematosus (NPSLE) is associated with adverse outcomes; however, imaging abnormalities are only detectable by conventional brain magnetic resonance imaging (MRI) in up to 50% of patients. This study investigated the variability in cortical thickness and diffusion tensor imaging (DTI) parameters among patients with NPSLE whose brain morphology appeared normal on conventional MRI. METHODS: This retrospective study enrolled 27 female patients with NPSLE (median age: 41.0 years, range: 22-63 years) and 34 female healthy controls (median age: 37.0 years, range: 24-55 years). None exhibited evident abnormalities on conventional MRI. Regional volumes, cortical thickness, and DTI parameters, including fractional anisotropy (FA) and mean diffusivity (MD), were compared. Age-adjusted multivariable logistic regression analysis was conducted to detect significant NPSLE-associated differences. RESULTS: No significant differences in grey or white matter volume fractions were observed between the groups. However, the NPSLE group demonstrated significant cortical thinning in the right pars opercularis (2.45 vs 2.52 mm, p = 0.007), reduced FA values in the fornix (0.35 vs 0.40, p = 0.001) and left anterior limb of internal capsule (0.50 vs 0.52, p = 0.012), and increased MD in the fornix (1.71 vs 1.48, p = 0.009) and left posterior corona radiata (0.80 vs 0.76, p = 0.005) compared with those of healthy controls. CONCLUSIONS: Cortical thickness measurements and DTI analyses can be used to detect differential variations in patients with NPSLE who exhibit an otherwise normal brain structure on conventional MRI, indicating the existence of subtle changes despite the absence of obvious macrostructural central nervous system involvement of lupus.

Correction: The development of surgical risk score and evaluation of necrotizing soft tissue infection in 161 Naja atra envenomed patients.

[This corrects the article DOI: 10.1371/journal.pntd.0010066.].

The Risk of Major Adverse Cardiovascular Events in Ankylosing Spondylitis Patients With a History of Acute Anterior Uveitis: A Nationwide, Population Based Cohort Study.

Background: To investigate the association between a history of acute anterior uveitis (AAU) and the risk of major adverse cardiovascular events (MACE) among patients with ankylosing spondylitis (AS). Methods: We identified 38,691 newly diagnosed AS patients between 2003 and 2013 from the Taiwan National Health Insurance Research Database. The exposure group was defined as people with uveitis diagnosis by ophthalmologist before AS diagnosis date. The incidence of MACE in patients with AS according to the International Classification of Diseases, Ninth Revision. We randomly selected a comparison group without a history of AAU at a 1:4 ratio matched by age, sex, and index year in relation to the risk of developing MACE. We used cox proportional hazard regression model to compare the risk of MACE between groups, shown as adjusted hazard ratios (aHRs) with 95% confidence intervals (CI). Further subgroup analysis and sensitivity tests were also performed. Results: There were 3,544 patients in the AAU group and 14,176 patients in the non-AAU group. The aHR of MACE for the AAU group was 0.79 (95% CI = 0.57-1.10) at a 1:4 ratio for age, sex and index year. Sensitivity analyses using various adjustment variables showed consistent results. Cox proportional hazard regression model demonstrated that use of non-steroidal anti-inflammatory drugs (NSAIDs) was associated with an increased risk of MACE in this cohort (HR = 3.44; 95% CI = 2.25-5.25). Conclusion: This cohort study showed that subjects with AAU was not associated with the risk of MACE among AS patients, compared to non-AAU controls.

The BASDAI Cut-Off for Disease Activity Corresponding to the ASDAS Scores in a Taiwanese Cohort of Ankylosing Spondylitis.

Objectives: The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) has been widely utilized to evaluate disease activity in patients with ankylosing spondylitis (AS) by an arbitrary cut-off of ≥4 to indicate high disease activity and initiate biological therapy. The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a new composite index to assess AS disease activity states that have been defined and validated. ASDAS ≥2.1 was selected as a criterion to start biological therapy. The purpose of this study was to estimate the corresponding BASDAI and ASDAS cut-off in a Taiwanese AS cohort. Methods: From November 2016 to October 2018, we assessed the ASDAS and the BASDAI regularly and recorded demographic data for 489 AS patients in Taichung Veterans General hospital (TCVGH) using an electronic patient-reported data system linked to electronic medical records. We used receiver operating characteristic curves with Youden's J statistic to determine the BASDAI values that correspond to ASDAS disease activity cut-offs (i.e., 1.3, 2.1, and 3.5). Results: In our population, the best trade-off BASDAI values corresponding to ASDAS -C-reactive protein (CRP) 1.3, 2.1, and 3.5 were 2.1, 3.1, and 3.7, respectively. The optimal BASDAI values corresponding to ASDAS-erythrocyte sedimentation rates 1.3, 2.1, and 3.5 were 2.0, 2.6, and 4.8, respectively. Conclusion: We propose a revised BASDAI cut-off based on our data, as BASDAI scores are commonly used globally. A more reasonable, lower BASDAI cut-off to initiate or change biological therapy will bring us closer to better decisions to treat AS patients.

Bilateral Lower Limbs Cellulitis: A Narrative Review of an Overlooked Clinical Dilemma.

Bilateral lower limbs cellulitis is a rare clinical condition, which has been overlooked for a long time. In daily clinical practice, bilateral cellulitis is a sporadically encountered condition; however, it remains a clinical challenge. There is a broad differential diagnosis for this clinical entity, and there is a lack of accepted international diagnostic criteria. Unnecessary antibiotic prescription is common, which has led to an emerging problem. In this review, we summarize case reports of bilateral lower limbs cellulitis and common pathogens that have been documented.

Mechanisms of Tumor Necrosis Factor-Alpha Inhibitor-Induced Systemic Lupus Erythematosus.

Systemic lupus erythematosus induced by biologics mainly results from tumor necrosis factor-alpha remains unclear. The objectives of the study were to investigate the mechanisms of tumor necrosis factor-alpha inhibitor-induced systemic lupus erythematosus. Peripheral blood mononuclear cells obtained from thirteen psoriasis patients were cultured and treated with the following: untreated control, Streptococcus pyogenes with or without different biologics. The supernatants were collected for cytokines assay. Analysis of cytokine expression revealed that IL-2 and IL-10 levels decreased only in the TNF-α inhibitor-treated groups but not in the groups treated with biologics involving IL-17, IL-12/IL-23 or IL-23 inhibitor mechanisms (p < 0.001, p < 0.05). The IFN-γ/IL-13 ratio increased significantly in patients with SLE inducing biologics to S. pyogenes induction only compared with non-SLE inducing biologics to S. pyogenes induction only (p = 0.001). IL-2 and IL-10 depletion and a shift to the Th-1 pathway in the innate response are the correlated mechanism for tumor necrosis factor-alpha inhibitor-induced systemic lupus erythematosus.

A potential life-threatening Asian funnel-web spider bite (Macrothele gigas) in central Taiwan.

Five funnel-web spiders in the genus Macrothele are widely distributed to Taiwan. We herein reported the severe case of a woman bitten by a male Macrothele gigas who present with autonomic (i.e., profuse sweating and piloerection), cardiovascular (hypertension and tachycardia), and neurologic effects (perioral numbness) in addition to local tissue swelling and regional limb pain. Morphine and ampicillin/sulbactam were administered. Her cardiovascular, neurologic, and local symptoms gradually improved, and thus was discharged 24 h post-bite. However, persistent diaphoresis and piloerection lasted for at least 3 days, and pre-renal azotemia was suspected. Due to the risk of severity and death reported for the Australian funnel web spider bites, we suggest patients bitten by an Asian funnel-web spider be carefully monitored and resuscitation performed as indicated.

The development of surgical risk score and evaluation of necrotizing soft tissue infection in 161 Naja atra envenomed patients.

BACKGROUND: Naja atra bites cause wound necrosis, secondary infection, and necrotizing soft tissue infection (NSTI) requiring repetitive surgeries. Little information is known about the predictors for surgery after these bites. MATERIALS AND METHODS: We retrospectively evaluated 161 patients envenomed by N. atra, 80 of whom underwent surgery because of wound necrosis and infection. We compared the patients' variables between surgical and non-surgical groups. To construct a surgical risk score, we converted the regression coefficients of the significant factors in the multivariate logistic regression into integers. We also examined the deep tissue cultures and pathological findings of the debrided tissue. RESULTS: A lower limb as the bite site, a ≥3 swelling grade, bullae or blister formation, gastrointestinal (GI) effects, and fever were significantly associated with surgery in the multivariate logistic regression analysis. The surgical risk scores for these variables were 1, 1, 2, 1, and 2, respectively. At a ≥3-point cutoff value, the model has 71.8% sensitivity and 88.5% specificity for predicting surgery, with an area under the receiver operating characteristic curve of 0.88. The histopathological examinations of the debrided tissues supported the diagnosis of snakebite-induced NSTI. Twelve bacterial species were isolated during the initial surgery and eleven during subsequent surgeries. DISCUSSION AND CONCLUSIONS: From the clinical perspective, swelling, bullae or blister formation, GI effects, and fever appeared quickly after the bite and before surgery. The predictive value of these factors for surgery was acceptable, with a ≥3-point risk score. The common laboratory parameters did not always predict the outcomes of N. atra bites without proper wound examination. Our study supported the diagnosis of NSTI and demonstrated the changes in bacteriology during the surgeries, which can have therapeutic implications for N. atra bites.

Ultrasound-aided diagnosis of preclinical phases of psoriatic arthritis in biologic-naïve psoriasis patients with or without arthralgia.

OBJECTIVES: The evolution of psoriasis (PsO) to psoriatic arthritis (PsA) has been proposed recently. There are three phases that occur in sequence prior to classifiable PsA: PsO patients, PsO patients with a positive imaging, and PsO patients with arthralgia not explained by other diagnosis. The purpose of this study was to compare the differences among preclinical phases using ultrasound and clinical assessment. METHODS: Patients with psoriasis were recruited. Patients who had been previously diagnosed with psoriatic arthritis or who had used biologics were excluded. A 52-joint ultrasound (52j US) assessment and clinical assessments including the swollen joint count, tender joint count, erythrocyte sediment rate, C-reactive protein, dactylitis score, enthesitis score, psoriasis severity, and nail psoriasis severity, were performed. RESULTS: A total of 188 eligible psoriasis patients were enrolled. Physical examination revealed 39 patients (20%) with at least one swollen joint. The 52j US assessment demonstrated 90 patients (47%) having at least one joint with grey-scale score 2-3. All patients were further stratified into PsO patients (n=58), PsO patients with a positive imaging, (n=59), PsO patients with arthralgia not explained by other diagnosis (n=27), and classifiable PsA (n=39). There were no differences in clinical characteristics other than tender joint count found among the three preclinical phases of PsA. Dactylitis score, swollen joint count and heatly assessment questionnaire score were significantly higher in classifiable PsA. CONCLUSIONS: Nearly half of the psoriasis patients without previously diagnosed psoriatic arthritis would be classified into the preclinical phases of psoriatic arthritis based on the 52j US and clinical assessments. Ultrasound assessment is helpful for identifying psoriasis patients who are in the preclinical phases of psoriatic arthritis, particularly for those without arthralgia.