Activity Score Research Articles

Assessing disparities through missing race and ethnicity data: results from a juvenile arthritis registry.

Ensuring high-quality race and ethnicity data within the electronic health record (EHR) and across linked systems, such as patient registries, is necessary to achieving the goal of inclusion of racial and ethnic minorities in scientific research and detecting disparities associated with race and ethnicity. The project goal was to improve race and ethnicity data completion within the Pediatric Rheumatology Care Outcomes Improvement Network and assess impact of improved data completion on conclusions drawn from the registry. This is a mixed-methods quality improvement study that consisted of five parts, as follows: (1) Identifying baseline missing race and ethnicity data, (2) Surveying current collection and entry, (3) Completing data through audit and feedback cycles, (4) Assessing the impact on outcome measures, and (5) Conducting participant interviews and thematic analysis. Across six participating centers, 29% of the patients were missing data on race and 31% were missing data on ethnicity. Of patients missing data, most patients were missing both race and ethnicity. Rates of missingness varied by data entry method (electronic vs. manual). Recovered data had a higher percentage of patients with Other race or Hispanic/Latino ethnicity compared with patients with non-missing race and ethnicity data at baseline. Black patients had a significantly higher odds ratio of having a clinical juvenile arthritis disease activity score (cJADAS10) of ≥5 at first follow-up compared with White patients. There was no significant change in odds ratio of cJADAS10 ≥5 for race and ethnicity after data completion. Patients missing race and ethnicity were more likely to be missing cJADAS values, which may affect the ability to detect changes in odds ratio of cJADAS ≥5 after completion. About one-third of the patients in a pediatric rheumatology registry were missing race and ethnicity data. After three audit and feedback cycles, centers decreased missing data by 94%, primarily via data recovery from the EHR. In this sample, completion of missing data did not change the findings related to differential outcomes by race. Recovered data were not uniformly distributed compared with those with non-missing race and ethnicity data at baseline, suggesting that differences in outcomes after completing race and ethnicity data may be seen with larger sample sizes.

Profiles of cytokines in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

This study aimed to identify plasma biomarkers that are significantly altered in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and are closely associated with AAV disease activity, as well as to explore their role in the pathogenesis of AAV. Cytokines were measured using Human Immune Response Panel 80-Plex in plasma from 59 patients with AAV and 20 healthy controls (HCs). The differentially expressed cytokines between the two groups and the possible signaling pathway involved in the pathogenesis of AAV were analyzed by bioinformatics. Relationship analysis was performed between these cytokines and clinical parameters to identify the biomarkers that can effectively indicate disease activity. We identified 65 differentially expressed cytokines between the two groups. Among them, 43 cytokines significantly affected the risk of AAV. Bioinformatic analysis showed that the 43 cytokines were primarily enriched in signaling pathways such as cytokine-cytokine receptor interaction, viral protein interaction with cytokine and cytokine receptor, chemokine signaling pathway, and IL-17 signaling pathway. The levels of 25 cytokines were significantly positively correlated with Birmingham Vasculitis Activity Score (BVAS), and the levels of 2 cytokines were significantly negatively correlated with BVAS. Receiver operating characteristic analysis showed that 9 cytokines can distinguish between disease relapse and remission (PTX3: area under curve (AUC)=0.932, IL34: AUC=0.856, IL2RA: AUC=0.833, CCL23: AUC=0.826, VEGFA: AUC=0.811, TNFSF13: AUC=0.795, Granzyme A: AUC=0.788, CSF3: AUC=0.773 and IL1A: AUC=0.765). The elevated levels of these 9 cytokines suggested a risk of disease relapse. The AUC of CCL11 in disease relapse and remission was 0.811 (p=0.0116). Unlike the other 9 cytokines, a negatively association existed between CCL11 level and the risk of disease relapse. A group of cytokines that may be involved in AAV pathogenesis was identified. Increased PTX3, IL34, IL2RA, CCL23, and VEGFA levels correlate with active disease in AAV and may be used as biomarkers to identify the disease relapse of AAV.

Impact of inflammation on cognitive function in patients with highly inflammatory rheumatoid arthritis

ObjectiveTo evaluate cognitive function in patients with rheumatoid arthritis (RA) and inflammatory activity.Patients and methodsWe performed a cross-sectional study of a cohort of patients with RA initiating their first biological...

Biological use influences the impact of inflammation on risk of major adverse cardiovascular events in rheumatoid arthritis

ObjectivesChronic inflammation promotes cardiovascular risk in rheumatoid arthritis (RA). Biological disease-modifying antirheumatic drugs (bDMARDs) improve disease activity and cardiovascular disease outcomes. We explored whether bDMARDs influence the impact of disease...

The relationship between intervertebral disc pathologies and the use of digital devices and lack of physical activity in adolescents

Background/Aim: Existing research on herniated discs in adolescents primarily focuses on surgical interventions and outcomes, with fewer studies investigating the effectiveness of non-surgical therapies. The correlation between obesity, facet tropism, lumbosacral transitional vertebrae, trauma, certain sports activities, and herniated discs in adolescents is well-documented. Comparable to adults, a sedentary lifestyle in adolescents potentially carries a significant risk of developing disc degeneration and herniation. Consequently, this study aims to examine the relationship between increased digital device usage, decreased physical activity, and the onset of disc pathologies in adolescents. Methods: The study group included 94 patients aged between 10 and 16 years diagnosed with cervical (CDH), thoracic (TDH), and lumbar (LDH) disc disease. For each participant, the individual daily usage time spent on desktop computers, tablets, laptops, and mobile phones and the total time spent on all digital devices were evaluated. Their level of physical activity was also assessed using the International Physical Activity Questionnaire – Short Form (IPAQ-SF). The study eliminated causes such as listhesis, facet tropism, lumbosacral transitional vertebra, trauma, and sports injuries that could prompt the development of these spinal pathologies. Additionally, other conditions that might cause spinal pain, such as scoliosis, rheumatological diseases with spinal involvement, tumors, and myofascial pain, were also ruled out. Results: The average age of all patients was 13.44 (2.07) years. A majority were women (n=55), comprising 58.50% of the sample. Of the patients, 60.64% had CDH, 12.77% had TDH, and 75.53% had LDH. The amount of physical activity and time spent on digital devices were similar across both genders (P=0.194 and P=0.770). A significant correlation was found between CDH and the time spent on tablets, laptops, and mobile phones (P<0.001). Again, a significant correlation was observed between LDH, usage of desktop computers, total time spent on all digital devices, and the IPAQ-SF score for low physical activity (P<0.001). Conclusion: The prevalence and duration of digital device use among adolescents are increasing, while physical activity is decreasing. Our study indicates that this situation may be linked to the development of disc degeneration and hernias. Understanding this association can help reduce treatment and rehabilitation costs and prevent the potential loss of workability and quality of life resulting from a herniated disc. Consequently, additional comparative research on this topic is crucial.

EULAR recommendations 2023 on the treatment of systemic lupus erythematosus-Implications for treatment in Germany

The 2023 update of the EULAR recommendations for the management of systemic lupus erythematosus (SLE) faced several tasks: the newly approved medications anifrolumab and voclosporin as well as the additional approval of belimumab for lupus nephritis had to be conceptionally fitted into the management of SLE. Novel data on hydroxychloroquine and glucocorticoids, additional results for the treat-to-target goals remission and low disease activity and experience with respect to vaccinations and infections had to be considered. Additionally, EULAR specified aslightly modified structure. The update was further developed with 5overarching principles and 13recommendations. An SLE activity score is required for each patient visit. All SLE patients should receive hydroxychloroquine at atarget dose of 5 mg/kg body weight. Glucocorticoids should only be used if necessary and reduced to not more than 5 mg prednisone equivalent daily in the long-term or, even better, tapered off. If the target of remission or low disease activity is not reached, methotrexate, azathioprine, mycophenolate and/or belimumab or anifrolumab should be used. For lupus nephritis, Euro-Lupus cyclophosphamide or mycophenolate are options for induction therapy and mycophenolate or azathioprine for maintenance. In the case of severe nephritis, the addition of belimumab or acalcineurin inhibitor (voclosporin or tacrolimus) should be considered. It is important that treatment should be continued for at least 3years. This review article describes the details of the new recommendations against the background of relevant studies in recent years and classifies them in the clinical context.

Mitochondrial control of proteasomal Psmb5 drives the differentiation of tissue-resident memory T cells in patients with rheumatoid arthritis.

To explore T-cell-intrinsic mechanisms underpinning the mal-differentiation of tissue-resident memory T (Trm) cells in patients with rheumatoid arthritis (RA). Circulating T cells from RA patients and healthy individuals were used for Trm cell differentiation. The role of Hobit in Trm differentiation was investigated through targeted silencing experiments. Psmb5 expression regulation was explored by identifying BRD2 as a key transcription factor, with the interaction validated through ChIP-qPCR. The impact of BRD2 succinylation on Trm differentiation was examined by manipulating succinyl-CoA levels in T cells. Humanized NSG chimeras representing synovitis provided insights into Trm infiltration in RA synovitis and were utilized for translational experiments. In RA patients, a notable predisposition of CD4+ T cells towards differentiation into Trm cells was observed, demonstrating a positive correlation with the Disease Activity Score 28. Remarkably, Hobit was a pivotal facilitator in the formation of RA CD4+ Trm cells. Mechanistic studies unveiled the dysregulation of proteasomal Psmb5 in T cells of RA patients as the key factor contributing to elevated Hobit protein levels. The deficiency of proteasomal Psmb5 was intricately linked to BRD2, with succinylation exerting a significant impact on Psmb5 transcription and Trm cell differentiation. This heightened BRD2 succinylation was attributed to elevated levels of mitochondrial succinyl-CoA in RA T cells. Consequently, targeting succinyl-CoA within CD4+ T cells controlled the inflammation of synovial tissues in humanized chimeras. Mitochondrial succinyl-CoA fosters the succinylation of BRD2, resulting in compromised transcription of proteasomal Psmb5 and the differentiation of Trm cells in RA.

Formulation of prebiotic, low glycemic index millet soups using foxtail, barnyard and kodo millet

Optimization of foxtail, barnyard, and kodo millet, was carried out to formulate millet soup mix by adopting a mixture design. The physico chemical parameters such as pH, Total Soluble Solids (TSS), viscosity, color values (L*, a*, b*), quality characteristics such as soluble, insoluble total fiber, reducing sugar, total phenolic content, and various sensory parameters such as appearance, colour, aroma, taste, and overall acceptability were recorded to assess the effect of selected above three millets on the reconstituted millet soups. Optimization was done and a polynomial model was developed using Response Surface Methodology (RSM) relating to total fiber, antioxidant activity, prebiotic activity score, glycemic index and overall acceptability of the millet soups. Results revealed that there was a significant difference (p < 0.05) observed in the in the pH, TSS, viscosity among ten variations of millet soups. Similar statistical significance (p < 0.05) was noticed in the colour values. Quality characters such as reducing sugar, insoluble, and soluble dietary fiber values were also found to be different between the ten millet soup variations. Highest value of total phenolic content was recorded in MS6 variation with 7.5 gm of barnyard and 7.5 gm kodo millet flour in the millet soup. The overlay plots were used to attain the optimum formulation for the millet soups related to total dietary fiber, antioxidant activity, prebiotic score, glycemic index and overall acceptability which created the yellow region based on the optimized value. The results revealed that the optimum values for the predicted responses were 5.65 g, 24.96%, 0.36, 41.85, 7.65 for the total dietary fiber, antioxidant activity, prebiotic score, glycemic index and overall acceptability, respectively, which was attained from the optimum mixture of 2.14 gm foxtail millet flour, 5.76 gm barnyard millet flour, and 7.11 gm kodo millet flour. From the results the optimized millet soup can be categorized as low glycemic soup (GI < 55) with good prebiotic activity.

The relationship between serum transglutaminase-2 levels and the severity of chronic spontaneous urticaria

Chronic spontaneous urticaria (CSU) is an immunological disease that is depicted by high prevalence and eminent burden for patients and society that is attributable to the arbitrary nature of symptoms and inconsistent tools for assessment of activity and severity. Transglutaminase-2 (TG2) is a posttranslational enzyme that is pervasively expressed in many cells and tissue types including mast cells. It has various biological functions, and its role in allergic disorders has been highlighted and delineated through several postulated mechanisms. This case–control study aimed at determining the relationship between serum levels TG2 and severity of CSU. To the best of our knowledge, this is the first study in Egypt to determine the relationship between serum TG2 and severity of CSU. We enrolled 60 adult patients with confirmed diagnosis of CSU. According to urticaria activity score (UAS), patients were categorized into three groups [20 with mild disease; UAS = 0, 20 with moderate disease; UAS = 1–3, 20 with severe disease; UAS = 4–6]. Another 20 healthy individuals (age and gender matched) served as a control group. All patients were subjected to detailed medical history, clinical examination, complete blood count with differential, serum total IgE, CRP, ESR, TSH, ANA, liver and renal function tests. Serum level of TG2 was done by quantitative ELISA for all enrolled patients and controls. Serum TG2 is significantly higher in patients group compared to control group (P value < 0.001). Serum TG2 levels were significantly higher in patients with severe disease compared to patients with moderate or mild disease. This is illustrated by the significant positive correlation between serum TG2 and UAS (r 0.814 and P value 0.000). Moreover, serum TG2 accurately classified CSU patients into mild, moderate and severe subgroups: as regards differentiation between mild and moderate cases (sensitivity 70%, specificity 80%, PPV 77.8, NPV 72.7) and as for the differentiation between moderate and severe cases (sensitivity 95%, specificity 90%, PPV 90.5, NPV 94.7). Serum TG2 may have a pivotal role as a marker of severity in patients with CSU.

Circulating Malondialdehyde Is a Potential Biomarker for Predicting All-Cause Mortality during Follow-Up by Reflecting Comprehensive Inflammation at Diagnosis in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Background and Objectives: To investigate whether circulating malondialdehyde (cMDA) at diagnosis could contribute to reflecting cross-sectional comprehensive inflammation or vasculitis activity and further predicting all-cause mortality during follow-up in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Materials and Methods: This study included 78 patients with AAV. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were collected as indices reflecting cross-sectional comprehensive inflammation, whereas the Birmingham vasculitis activity score (bVAS), and the five-factor score (FFS) were reviewed as AAV-specific indices. All-cause mortality was considered to be a poor outcome during follow-up. cMDA was measured from stored sera. Results: The median age of the 78 patients (32 men and 46 women) was 63.0 years. The median BVAS, FFS, ESR, and CRP were 5.0, 0, 24.5 mm/h, and 3.4 mg/L, respectively. Six patients died during the median follow-up duration based on all-cause mortality at 26.7 months. At diagnosis, cMDA was significantly correlated with cross-sectional ESR but not with BVAS or FFS. Compared to patients with cMDA < 221.7 ng/mL, those with cMDA ≥ 221.7 ng/mL at diagnosis exhibited an increased relative risk (RR 12.4) for all-cause mortality and further showed a decreased cumulative patient survival rate. Cox analyses revealed that cMDA ≥ 221.7 ng/mL (hazard ratio 24.076, p = 0.007) exhibited an independent association with all-cause mortality during follow-up in patients with AAV. Conclusions: cMDA at diagnosis may be a potential biomarker for predicting all-cause mortality during follow-up by reflecting comprehensive inflammation at diagnosis in patients with AAV.

Safety and Efficacy of Upadacitinib in Patients with Rheumatoid Arthritis Refractory to Biologic DMARDs: Results Through Week 216 from the SELECT-CHOICE Study.

Thesafety and efficacy of upadacitinib 15mg (UPA15) through week 216 was evaluated in patients with rheumatoid arthritis (RA) from the long-term extension (LTE) of the phase 3 SELECT-CHOICE study. Patients with RA refractory to biologic disease-modifying antirheumatic drugs (bDMARDs) were randomized to UPA15 or abatacept (ABA) for 24weeks. During the open-label LTE, patients on ABA switched to UPA15 at week 24, and those on UPA15 continued treatment. Thesafety and efficacy of continuous UPA15, and ABA to UPA15, are summarized through week 216. The LTE was comprised of 91.4% (n = 277/303) of patients that initially received UPA15, and 89.6% (n =277/309) that initially received ABA. Of patients on UPA15 in the LTE (n =547), 28.3% (n =155/547) discontinued the study drug by week 216. Relative to other adverse events of special interest, and largely consistent with previous findings at week 24, higher rates of serious infection, COVID-19, herpes zoster, and elevated creatine phosphokinase were reported, while rates of malignancy excluding nonmelanoma skin cancer (NMSC), NMSC, major adverse cardiovascular event (MACE), and venous thromboembolism (VTE) were low. Long-term safety data with UPA through week 216 aligned with previous observations and no new safety risks were identified, including in patients who switched from ABA to UPA15. Proportions of patients achieving 28-joint disease activity score based on C-reactive protein (DAS28[CRP]) < 2.6/ ≤ 3.2, clinical disease activity index (CDAI) and simple disease activity index (SDAI) low disease activity/remission, ≥ 20%/50%/70% improvement in theAmerican College of Rheumatology (ACR20/50/70) response criteria, and Boolean remission were maintained or improved with UPA15 through week 216. Improvements in theHealth Assessment Questionnaire-Disability Index (HAQ-DI), patient's assessment of pain, and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were also maintained or improved with UPA15 through week 216. Across all efficacy endpoints, similar results were observed in patients who switched from ABA to UPA15 versus continuous UPA15. Patients with an inadequate response to ≥ 1 prior tumor necrosis factor (TNF) inhibitor (UPA15: n =263/303, 86.8%; ABA to UPA15: n =273/309, 88.3%) showed similar responses to the total population. The long-term safety profile of UPA was consistent with previous findings and the broader RA clinical program. Compared to the primary analyses at week 24, efficacy responses were maintained or further improved with UPA15 through week 216 in patients with RA. Trial registration, ClinicalTrials.gov identifier: NCT03086343.

Clinical Characteristics, Predictors for Mortality and Comparison of the Birmingham Vasculitis Activity Score and the Five-Factor Score on Survival in ANCA-Associated Vasculitis in Hong Kong

Objective: To describe the clinical profile and predictors of mortality of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients in Hong Kong. To compare the accuracy of the latest Five-Factor Score (FFS-2009) and the Birmingham Vasculitis Activity Score (BVAS) in prediction of survival with this local cohort. Methods: A retrospective observational study on newly diagnosed AAV patients, from January 1, 2011 to March 31, 2022, managed in the Kowloon West Cluster (KWC) hospitals in Hong Kong. Demographic and baseline characteristics, clinical profile, and treatment profile were reviewed. Factors associated with mortality were analyzed with the Cox proportional hazards model. The performances of FFS and BVAS in mortality prediction were analyzed by receiver operating characteristic (ROC) curves. Results: A total of 83 AAV patients were included in the study. The median age was 70.5 years at diagnosis. Microscopic polyangiitis (MPA; 69.9%) was the most common AAV subtype. The median FFS and BVAS were 2 and 20, respectively. The overall mortality was 45.6% across the study period. Multivariate Cox regression identified age at diagnosis (HR 1.043, [Formula: see text]), stabilized peak serum creatinine (HR 1.002, [Formula: see text]), hemoglobin level (HR 0.754, [Formula: see text]), cardiac involvement (HR 3.862, [Formula: see text]), and use of maintenance therapy (HR 0.261, [Formula: see text]) as independent predictors of overall survival. Both FFS and BVAS were significant predictors of overall survival. The areas under the curve (AUC) of ROC curves suggested FFS was a good prediction tool for early mortality in 1 year, with an AUC value of 0.874. Conclusion: Despite the advances in treatment, AAV still carried significant morbidities with high mortality. Clinical predictors and existing scoring systems showed good predictive power on mortality.

Volumetric measurement of terminal ileal Crohn's disease by magnetic resonance enterography: a feasibility study.

Magnetic resonance enterography (MRE) interpretation of Crohn's disease (CD) is subjective and uses 2D analysis. We evaluated the feasibility of volumetric measurement of terminal ileal CD on MRE compared to endoscopy and sMARIA, and the responsiveness of volumetric changes to biologics. CD patients with MRE and contemporaneous CD endoscopic index of severity-scored ileocolonoscopy were included. A centreline was placed through the terminal ileum (TI) lumen defining the diseased bowel length on the T2-weighted non-fat saturated sequence, used by two radiologists to independently segment the bowel wall to measure volume (phase 1). In phase 2, we measured disease volume in patients treated with biologics, who had undergone pre- and post-treatment MRE, with treatment response classified via global physician assessment. Phase 1 comprised 30 patients (median age 29 (IQR 24, 34) years). Phase 2 included 12 patients (25 years (22, 38)). In phase 1, the mean of the radiologist-measured volumes was used for analysis. The median disease volume in those with endoscopically active CD was 20.9 cm3 (IQR 11.3, 44.0) compared to 5.7 cm3 (2.9, 9.8) with normal endoscopy. The mean difference in disease volume between the radiologists was 3.0 cm3 (limits of agreement -21.8, 15.9). The median disease volume of patients with active CD by sMARIA was 15.0 cm3 (8.7, 44.0) compared to 2.85 cm3 (2.6, 3.1) for those with inactive CD. Pre- and post-treatment median disease volumes were 28.5 cm3 (26.4, 31.2), 11 cm3 (4.8, 16.6), respectively in biological responders, vs 26.8 cm3 (12.3, 48.7), 40.1 cm3 (10, 56.7) in non-responders. Volumetric measurement of terminal ileal CD by MRE is feasible, related to endoscopy and sMARIA activity, and responsive to biologics. Measuring the whole volume of diseased bowel on MRE in CD is feasible, related to how biologically active the disease is when assessed by endoscopy and by existing MRE activity scores, and is sensitive to treatment response. MRE reporting for CD is subjective and uses 2D images rather than assessing the full disease volume. Volumetric measurement of CD relates to endoscopic activity and shows reduced disease volumes in treatment responders. This technique is an objective biomarker that can assess disease activity and treatment response, warranting validation.

The Rate of Retreatment in Patients treated with teprotumumab: A Multicenter Study of 119 Patients with 1 year Follow Up

Objective or PurposeTo determine the rate of retreatment in patients who receive a full course of teprotumumab therapy for Thyroid Eye Disease (TED) and drivers of retreatment. DesignMulti center, retrospective study SubjectsAll patients who received a full course of treatment and had available data at 1 year post initial treatment were included. MethodsCharts were reviewed for the following information: age, gender, months since diagnosis of TED, smoking status, prior treatments. Further, the clinical activity score (CAS), proptosis and the Gorman diplopia score were reviewed at baseline, at the end of the first course and at baseline for the second course in those who received it. A logistic regression model was created to review the drivers of retreatment. Main Outcome MeasuresRate of retreatment and the drivers of retreatment. Results119 patients were included from 3 centers across the US. The overall retreatment rate was 24% (29/119). There was no difference between the 3 sites (p = 0.6). In univariate analyses, at baseline, there was no difference in proptosis (p = 0.07), diplopia score (p = 0.4) or duration of TED (p = 0.4), between retreated and non-retreated patients. From the retreated group, 82% had a significant proptosis response (≥ 2 mms reduction from baseline) following their initial course, while 68% of patients had a clinically significant proptosis response in the non-retreated group (p = 0.16). The use of other treatments prior to the first infusion of teprotumumab and baseline thyroid dysfunction, were not significantly different between the retreated and non-retreated groups (p = 0.06 and 0.09, respectively). The mean (SD) difference between the end of first treatment and at baseline prior to second treatment (in those who received it) was 2 (2) for CAS, 2 mms (4) for proptosis and 1 (1) for diplopia. Age as the only significant driver of retreatment (p < 0.05). Retreated patients were 7 years older than their non retreated counterparts (age 60 vs 53 (p < 0.05). ConclusionsIn patients receiving a full course of teprotumumab therapy, the rate of retreatment is 24%. Age is the only driver of retreatment.

In chronic spontaneous urticaria, increased Galectin-9 expression on basophils and eosinophils is linked to high disease activity, endotype-specific markers, and response to omalizumab treatment.

Galectin-9 (Gal-9) has been implicated in allergic and autoimmune diseases, but its role and relevance in chronic spontaneous urticaria (CSU) are unclear. To characterize the role and relevance of Gal-9 in the pathogenesis of CSU. We assessed 60 CSU patients for their expression of Gal-9 on circulating eosinophils and basophils as well as T cell expression of the Gal-9 receptor TIM-3, compared them with 26 healthy controls (HCs), and explored possible links with disease features including disease activity (urticaria activity score, UAS), total IgE, basophil activation test (BAT), and response to omalizumab treatment. We also investigated potential drivers of Gal-9 expression by eosinophils and basophils. Our CSU patients had markedly increased rates of circulating Gal-9+ eosinophils and basophils and high numbers of lesional Gal-9+ cells. High rates of blood Gal-9+ eosinophils/basophils were linked to high disease activity, IgE levels, and BAT negativity. Serum levels of TNF-α were positively correlated with circulating Gal-9+ eosinophils/basophils, and TNF-α markedly upregulated Gal-9 on eosinophils. CSU patients who responded to omalizumab treatment had more Gal-9+ eosinophils/basophils than non-responders, and omalizumab reduced blood levels of Gal-9+ eosinophils/basophils in responders. Gal-9+ eosinophils/basophils were negatively correlated with TIM-3+TH17 cells. Our findings demonstrate a previously unrecognized involvement of the Gal-9/TIM-3 pathway in the pathogenesis CSU and call for studies that explore its relevance.

The modified suture-bridge technique for treating avulsion fracture of minors tibial eminence of anterior cruciate ligament: a retrospective study

PurposeThis study aimed to evaluate the clinical and radiological outcomes of modified suture-bridge technique fixation for anterior cruciate ligament (ACL) tibial avulsion fracture.MethodMinors who underwent arthroscopic reduction and modified suture bridge fixation of ACL tibial avulsion fracture between January 2018 and January 2022 were retrospectively analyzed. Postoperative MRI and X-ray examinations were performed to evaluate the presence of epiphyseal plate injury and fracture healing. Moreover, KT-1000 side-to-side difference, Lachman test, range of motion (ROM), the subjective Knee score of the International Knee Documentation Committee (IKDC), Lysholm Knee score, and Tegner activity grade score were evaluated preoperatively and at the minimum 1-year follow-up visit.ResultsA total of 16 participants met the inclusion criteria. They had a mean age of 12.6 years (range, 9–16 years); mean time to surgery, 6.9 days (range, 2–13 days) and had a minimum of 12 months clinical follow-up (mean, 25.4 months; range, 12–36 months) after surgery. Postoperative radiographs and MRI showed no injury to the epiphyseal plate, optimal reduction immediately after the operation, and bone union within three months in all patients. All of the following showed significant improvements (pre- vs. postoperatively): mean KT-1000 side-to-side difference (8.6 vs. 1.5; p < 0.05), Lachman tests (2 grade 9 and 3 grade 7 vs. 0 grade 12 and 1 grade 4; p < 0.05), IKDC subjective score (48.3 vs. 95.0; p < 0.05), mean Lysholm score (53.9 vs. 92.2; p < 0.05), mean Tegner activity score (3.2 vs. 8.3; p < 0.05) and mean ROM (42.9°vs 133.1°; p < 0.05).ConclusionArthroscopic reduction and modified suture bridge fixation for ACL tibial avulsion fracture is a dependable and recommended treatment that can effectively restore the stability and function of the knee and is worthy of clinical promotion.

Knowledge of Patients' Activation Level Changes Expert US Physicians' Communication in GERD Management.

Gastroesophageal reflux disease (GERD) is common. Treatment is to manage symptoms, but medication nonadherence is common. To date, little emphasis has been on understanding patient behaviors and reasons for medication nonadherence. We performed a cross-sectional survey study among expert gastroenterologists specializing in esophageal disease. Survey studies consisted of a 6-item questionnaire measuring physician knowledge of patient activation, the Clinician Support for Patient Activation Measure (CS-PAM), and an adapted 20-item Patient Assessment of Chronic Illness Care (PACIC). All question stems were specified to GERD management. Thirty-six experts participated. Most indicated hearing the term patient engagement before this survey (88.9%), but fewer were aware of the term patient activation (33.3%). Respondents were then made aware of the clinical significance of patient activation and asked, based on this knowledge, the likelihood that patients' activation level before the clinic would impact their communication. Responses varied between "to a great extent" and "not at all." Overall, CS-PAM activation scores were high, indicating a high level of support for patient activation. Lastly, respondents indicated their frequency of participating in partnership-building behaviors with patients. More than half (52.8%) of expert physicians "almost always" asked how GERD affected their lives, while less often asked patients about their health habits (22.2%), help set specific goals to improve their eating or exercise lifestyle (19.4%), or refer patients to a dietician, health educator, or counselor for their GERD (11.1%). Patient activation is an important strategy and may provide a behavioral approach to address medication adherence in GERD.

Q2-metnet: QIIME2 package to analyze 16S rRNA data via high-quality metabolic reconstructions of the human gut microbiota.

16S rRNA gene sequencing is the most frequent approach for the characterization of the human gut microbiota. Despite different efforts in the literature, the inference of functional and metabolic interpretations from 16S rRNA gene sequencing data is still a challenging task. High-quality metabolic reconstructions of the human gut microbiota, such as AGORA and AGREDA, constitute a curated resource to improve functional inference from 16S rRNA data, but they are not typically integrated into standard bioinformatics tools. Here, we present q2-metnet, a QIIME2 plugin that enables the contextualization of 16S rRNA gene sequencing data into AGORA and AGREDA. In particular, based on relative abundances of taxa, q2-metnet determines normalized activity scores for the reactions and subsystems involved in the selected metabolic reconstruction. Using these scores, q2-metnet allows the user to conduct differential activity analysis for reactions and subsystems, as well as exploratory analysis using PCA and hierarchical clustering. We apply q2-metnet to a dataset from our group that involves 16S rRNA data from stool samples from lean, allergic to cow's milk, obese and celiac children, and the Belgian Flemish Gut Flora Project cohort, which includes faecal 16S rRNA data from obese and normal-weight adult individuals. In the first case, q2-metnet outperforms existing algorithms in separating different clinical conditions based on predicted pathway abundances and subsystem scores. In the second case, q2-metnet complements competing approaches in predicting functional alterations in the gut microbiota of obese individuals. Overall, q2-metnet constitutes a powerful bioinformatics tool to provide metabolic context to 16S rRNA data from the human gut microbiota. Python code of q2-metnet is available in https://github.com/PlanesLab/q2-metnet and https://figshare.com/articles/dataset/q2-metnet_package/26180446. Supplementary data are available at Bioinformatics online.

Effect of Multiple Types of High-fat Diet Induction on Gut Microbiota Profile and Butyrate Levels on NAFLD Rat Model

Dysbiosis, marked by a decline in Firmicutes (such as Clostridium spp.) and a rise in Proteobacteria (such as Escherichia coli), is recognized as a pathway linked to the progression of non-alcoholic fatty liver disease (NAFLD). High-fat food may influence the development of NAFLD. This study investigates the effect of different high-fat diets on gut microbiota composition and butyrate levels in a rat model. Four groups of Rattus norvegicus strain Wistar (n=27) were fed specific diets for 12 weeks: normal diet (ND, n=7), high-fat diet (HFD, n=6), western diet (WD, n=7), and high-fat-high-fructose diet (HFHFD, n=7). Stools were cultured on Eosin Methylene Blue (EMB) for Escherichia coli and Forget Fredette Agar (FFA) for Clostridium spp. Colonies were counted using Total Plate Count (TPC), and butyrate levels were measured with gas chromatography. Liver histology was assessed with the NAFLD activity score (NAS). Gut microbiota were analyzed using Crosstab and Chi-Square tests, and butyrate levels with the Kruskal-Wallis test. Butyrate levels decreased in NAFLD-inducing diet groups (HFD, WD, HFHFD) compared to ND (p=0.021). Escherichia coli colony counts were significantly higher in NAFLD-inducing diet groups (p=0.048), while Clostridium spp. counts were higher in ND (p=0.001). Liver histological changes, particularly in the WD group, resembled NAFLD. These findings imply that different high-fat diets can alter the gut microbiome, potentially influencing NAFLD development.

Study of Prebiotic Potency Sweet Potato Flour With Difference of Varieties as Complementary Feeding

Infant’s complementary feeding innovation by using the local food Ipomoea Batatas with four variants they are orange, purple, yellow and white. Purpose of the research was to determine the potency prebiotic, from four flour variants. Design of the research was experimental study with completely random design. The research was operated on June until October of 2022 at Laboratory of Abdurrab University. Steps of the research were by the flour making, and the prebiotic potency test. The data was analyzed by Huebner’s method to know the prebiotic’s activity score. The research’s outcome was existence of the bacteria amount increasing of L.parasei for the purple Ipomoea Batatas (8,54 log CFU mL-1). The purple Ipomoea Batatas contained better prebiotic potency than orange, yellow and white Ipomoea Batatas.