RESUMEN

Proliferative diabetic retinopathy (PDR) is a vision-threatening complication of diabetes mellitus (DM). Anterior chamber (AC) flare and intraocular cytokines are potent biomarkers reflecting the intraocular immune status in PDR. This study aimed to elucidate the complex interrelationship between AC flare and intraocular cytokines in PDR eyes. A retrospective observational study was conducted on 19 PDR eyes of 19 patients with type 2 DM, and on 19 eyes of 19 patients with idiopathic macular hole or epiretinal membrane as controls. AC flare was measured before pars plana vitrectomy (PPV). Aqueous humor (AH) and vitreous fluid (VF) samples were collected at the time of PPV, and the quantities of 27 cytokines in both intraocular fluids were analyzed. In the PDR and control groups, Spearman's rank correlation analysis revealed a positive correlation between AC flare and IL-8 level in both AH and VF. Additionally, IL-8 levels in AH correlated positively with IL-8 levels in VF. In the PDR group, receiver operating characteristic curve analysis identified IL-8 level in AH as a significant predictor for both diabetic macular edema (DME) and vitreous hemorrhage (VH) complications. The cut-off values of IL-8 were established at ≥26.6 pg/mL for DME and ≥7.96 pg/mL for VH. Given the positive correlation between AC flare and AH IL-8 level, the present findings suggest that AC flare value may potentially be a non-invasive biomarker for predicting DME.

Asunto(s)

Cámara Anterior , Humor Acuoso , Retinopatía Diabética , Cuerpo Vítreo , Humanos , Retinopatía Diabética/inmunología , Retinopatía Diabética/metabolismo , Retinopatía Diabética/patología , Retinopatía Diabética/etiología , Masculino , Femenino , Cámara Anterior/patología , Cámara Anterior/metabolismo , Cámara Anterior/inmunología , Persona de Mediana Edad , Anciano , Humor Acuoso/metabolismo , Humor Acuoso/inmunología , Estudios Retrospectivos , Cuerpo Vítreo/metabolismo , Cuerpo Vítreo/patología , Edema Macular/etiología , Edema Macular/metabolismo , Edema Macular/inmunología , Edema Macular/patología , Vitrectomía , Biomarcadores , Citocinas/metabolismo , Interleucina-8/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/inmunología , Curva ROC

RESUMEN

Crohn's disease is a chronic inflammatory bowel condition causing symptoms, notably pain, due to ongoing intestinal inflammation or complications like abscesses, strictures, and fistulas, which are common in IBD patients. Abdominal pain affects up to 60 % of IBD patients, irrespective of disease severity, prompting medical attention. Various medications like NSAIDs, antidepressants, antispasmodics, anticonvulsants, and opioids are used to manage pain, but they have limited effectiveness and potential side effects, even during remission. In this case, a 20-year-old Caucasian female college student [height 5'4″, weight 120lbs (54.4 kg)] with juvenile idiopathic arthritis and Crohn's disease experienced severe daily abdominal pain, negatively impacting her life. Despite a multimodal regimen, including gabapentin, nortriptyline, duloxetine, and acetaminophen, her pain persisted, significantly affecting her appetite, sleep, mood, activity level, and overall quality of life (QOL). To address this, dorsal root ganglion (DRG) stimulation was considered. The patient aimed for a 20 % pain reduction and improved QOL. Trial leads were placed along the T10 and T12 DRG, resulting in a 25 % pain reduction (8-6 out of 10) and substantial QOL improvement. She could eat, sleep without interruptions, walk longer distances, and be more active. The T12 lead was more effective than the T10, targeting upper abdomen stimulation. The patient and her mother were highly satisfied and opted for permanent implantation for the T11 and T12 DRG. While DRG stimulation was approved in 2016 for chronic pain, to our knowledge, this is the first reported case of its use in a patient with debilitating Crohn's disease.

RESUMEN

BACKGROUND AND PURPOSE: There are concerns for safety regarding SARS-CoV-2 vaccines for patients with autoimmune neuromuscular disease. We compared daily functioning using disease-specific patient-reported outcome measures (PROMs) before and after SARS-CoV-2 vaccinations. METHODS: In this substudy of a prospective observational cohort study (Target-to-B!), patients with myasthenia gravis (MG), chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), and idiopathic inflammatory myopathy (IIM) vaccinated against SARS-CoV-2 were included. Surveys of daily functioning (Myasthenia Gravis Activities of Daily Living, Inflammatory Rasch-Built Overall Disability Scale, Multifocal Motor Neuropathy Rasch-Built Overall Disability Scale, and Health Assessment Questionnaire-Disability Index) were sent before first vaccination and every 60 days thereafter for up to 12 months. Regression models were constructed to assess differences in PROM scores related to vaccination, compared to scores unrelated to vaccination. We also assessed the proportion of patients with deterioration of at least the minimal clinically important difference (MCID) between before first vaccination and 60 days thereafter. RESULTS: We included 325 patients (median age = 59 years, interquartile range = 47-67, 156 [48%] female sex), of whom 137 (42%) had MG, 79 (24%) had CIDP, 43 (13%) had MMN, and 66 (20%) had IIM. PROM scores related to vaccination did not differ from scores unrelated to vaccination. In paired PROMs, MCID for deterioration was observed in three of 49 (6%) MG patients, of whom none reported a treatment change. In CIDP, MCID for deterioration was observed in eight of 29 patients (28%), of whom two of eight (25%) reported a treatment change. CONCLUSIONS: SARS-CoV-2 vaccination had no effect on daily functioning in patients with autoimmune neuromuscular diseases, confirming its safety in these patients.

RESUMEN

BACKGROUND: Mucus plugs identified through chest computed tomography (CT) scans have emerged as potential prognostic factors in chronic obstructive pulmonary disease (COPD). This 5-year longitudinal study investigated their impact on exacerbations and FEV1 decline. METHODS: COPD patients with baseline chest CT and spirometric assessments were categorized based on mucus plug presence. Propensity-score matching yielded balanced groups. Exacerbation rates, time to exacerbation events, hazard ratio (HR) for exacerbations, and annual rates of FEV1 decline were evaluated. Sensitivity analysis was performed with stratification according to mucus plug scores of 0, 1-2, and ≥3. RESULTS: Among 623 eligible patients, the mucus plug group was 44.3%. Through 1:1 propensity-score matching, each group was comprised of 187 individuals with balanced covariates. The mucus plug group showed higher rates of moderate-to-severe (0.51/year vs. 0.58/year, P=0.035), severe exacerbations (0.21/year vs. 0.24/year, P=0.032), and non-eosinophilic exacerbations (0.45/year vs. 0.52/year, P=0.008). Mucus plugs were associated with increased hazard of moderate-to-severe (adjusted HR=1.502 [95% CI 1.116-2.020]), severe (adjusted HR=2.106 [95% CI, 1.429-3.103]), and non-eosinophilic exacerbations (adjusted HR=1.551 [95% CI, 1.132-2.125]). Annual FEV1 decline was accelerated in the mucus plug group (ß-coefficient=-62 [95% CI, -120 to -5], P=0.035). Sensitivity analysis showed higher risk of exacerbations and accelerated FEV1 decline in mucus plug score ≥3 compared to score 0. CONCLUSIONS: Mucus plugs are associated with increased risks of exacerbations, particularly non-eosinophilic, and accelerated FEV1 declines over 5 years. Our study identified the potential prognostic value of mucus plugs on future exacerbation risks and lung function decline trajectories.

RESUMEN

Purpose: To demonstrate and evaluate factors contributing to near-cures in patients with Gadolinium Deposition Disease (GDD) undergoing intravenous (IV) DTPA chelation. Methods: Patients who had undergone or are currently undergoing DTPA chelation for GDD were included in this report based on their medical records that showed their perceived improvement was at least 80% back to normal. A survey was developed that included factors commonly reported by patients treated in one clinic to determine if these 'near-cured' (pre-MRI baseline health) individuals possessed certain factors and lacked others. The anonymized survey was emailed to these individuals by the principal treating physician, the only investigator not blinded to the subjects. This report describes clinical documentation of patient status and their underlying factors in individuals treated by the primary author, and no research was performed. The survey was sent to sixteen individuals; Fourteen patients completed it (10 females; 41.1 ± 11.2 y/o). Results: The most common factor was the administration of ≤5 lifetime doses of a Gadolinium-Based Contrast Agents (GBCA) (12/14). Unconfounded agents triggering GDD were seen in nine subjects. Most subjects (12/14) initiated chelation in the first year after the causative GBCA, and most (11/14) underwent ≤10 chelations with DTPA. Good healthcare status prior to MRI was observed in 5 subjects. The majority (11/14) described their immune status as strong. Severe physical disability prior to chelation was seen in 1. Conclusion: Subjects with GDD can experience near-cure with IV DTPA chelation. Factors surveyed that predict near-cure include the start of chelation in the first year, few GBCA administrations, and good health status before MRI with GBCA injection. Nonetheless, a few patients with predictors of less successful outcomes still experienced near-cure.

RESUMEN

OBJECTIVES: To investigate the severe haematological involvement in children with SLE and assess its clinical associations, treatments, outcome and damage accrual. METHODS: The medical charts of children with SLE in whom haematological involvement was observed were reviewed. Severe haematological indices were defined as autoimmune haemolytic anaemia with a haemoglobin concentration < 8 g/dL, thrombocyte count < 30 000/µL, and neutrophil count < 500/µL. RESULTS: Among the 224 patients included, 102 (45.5%) displayed severe indices, predominantly at the initial involvement, and most frequently as severe anaemia in 54 (24.1%) and severe thrombocytopenia in 45 (20.1%). Disease activity did not differ according to the presence of severe disease indices. In addition, the presence of severe indices at initial involvement did not affect the damage accrual. However, a higher rate of damage (51.1% vs. 29.9%, p = 0.002) and steroid-induced damage (28.9% vs. 8.2%, p < 0.001) was evident in patients with flares of the haematological system. Regression analysis revealed that rituximab treatment during the initial episode (OR:4.5, p = 0.006) and the presence of anticardiolipin antibodies (OR:2.3, p = 0.014) significantly increases the odds for haematological system flare. However, severe indices at initial involvement did not increase the odds of a haematological flare. CONCLUSION: Severe haematological indices at onset are common but not related with disease outcomes. Prevention of flares is important to improve outcomes, and a more rigorous maintenance strategy would benefit most to children who display haematological indices refractory to conventional immunosuppressants and those with anti-cardiolipin antibodies.

RESUMEN

BACKGROUND/PURPOSE: Endoscopic remission is presently recognized as the standard therapeutic target in the treatment of ulcerative colitis (UC). However, achieving histological remission is increasingly viewed as a pivotal objective. This study investigates the effects of attaining completely histological remission on the clinical outcomes for UC patients with a high disease burden who have already reached endoscopic remission. This is the inaugural study to concentrate on this specific patient demographic. METHODS: This retrospective cohort study enrolled moderate-to-severe, biologics-experienced UC patients with completely endoscopic remission (Mayo endoscopic subscore of 0) between June 2017 and October 2023 at Chang Gung Memorial Hospital, Linkou. Patients were classified into histological remission (HR) and non-histological remission (non-HR) groups based on the Nancy index (NI). HR was defined as an NI score of 0, with all other patients categorized as non-HR. The definition of flare-ups was based on both clinical and endoscopic evidence. Comparative analyses focused on baseline characteristics and clinical outcomes at follow-up. RESULTS: A total of 42 patients (HR group: 23, non-HR group: 19) were included. The average follow-up duration was 17.6 months. Baseline characteristics were comparable between the groups. At the end of follow-up, the HR group showed a significantly lower rate of acute flare-ups (26.1% vs. 68.4%, P = 0.006). Although not statistically significant, the HR group also experienced fewer emergency department visits and hospital admissions. CONCLUSIONS: For moderate-to-severe, biologics-experienced UC patients in endoscopic remission, achieving completely histological remission is associated with a substantial reduction in flare-ups, suggesting its potential as a valuable therapeutic target.

RESUMEN

OBJECTIVES: The objective was to determine whether specific physical activity (PA) or psychological stress factors are associated with different definitions of flare-ups (pain-defined flares [PDFs]: periods of increased pain lasting at least 2 h, when pain intensity is distinctly worse than it has been recently; and non-pain-defined flares [NPDFs]: obviously uncomfortable feelings, such as fatigue, loss of function, or emotional/psychosocial fluctuations, without major fluctuations in pain intensity based on 11-point scales) among people with lumbar radicular pain. METHODS: This was a case-crossover study. Participants with acute or subacute lumbar radicular pain completed serial face-to-face or online assessments for 6 weeks at 3-day intervals to determine whether they experienced sciatica flare-ups (PDF/NPDF) after specific types of PA or psychological stresses. RESULTS: A total of 152 participants were enroled. There were 597 PDF and 323 NPDF case periods and 800 control periods. The odds of PDFs were increased by prolonged walking and standing, and the odds of NPDFs were increased by prolonged sitting, mental distress, and depressed mood. According to the multivariable analyses, prolonged sitting (OR: 3.0, 95% CI: 1.7-5.5), prolonged walking (OR: 6.2, 95% CI: 3.9-9.9), and prolonged standing (OR: 5.6, 95% CI: 3.3-9.5) were significantly associated with the odds of PDFs, and prolonged sitting (OR: 3.4, 95% CI: 1.8-6.2), mental distress (OR: 6.7, 95% CI: 2.5-17.5), and depressed mood (OR: 5.8, 95% CI: 2.6-12.8) associated with the odds of NPDFs. CONCLUSIONS: Prolonged sitting, walking, and standing triggered the occurrence of PDF. Prolonged sitting, mental distress, and depressed mood triggered the occurrence of NPDF.

Asunto(s)

Estudios Cruzados , Humanos , Masculino , Femenino , Persona de Mediana Edad , Factores de Riesgo , Adulto , Dolor de la Región Lumbar/psicología , Brote de los Síntomas , Estrés Psicológico , Ejercicio Físico , Caminata/fisiología , Ciática , Radiculopatía/fisiopatología , Radiculopatía/psicología , Sedestación , Dimensión del Dolor/métodos , Distrés Psicológico , Depresión

RESUMEN

OBJECTIVES: The recent Flare-OA questionnaire measuring flare in knee and hip osteoarthritis (OA) (19 items in 5 domains, numerical rating scale) showed good psychometric properties along with classical test theory. This study aimed to determine its scaling properties by Rasch analysis and to present evidence for a refined scalable version. STUDY DESIGN AND SETTING: The participants were 398 subjects (mean age 64 years [standard deviation = 8.1], 70.4% women) recruited from Australia, France, and the United States, with clinically and radiologically symptomatic knee or hip OA, who completed an online survey. The sample was split into derivation and validation subsamples, stratified by country and joint. Rasch analysis examined differential item functioning (DIF) for sex, age, country, and joint. A confirmatory factor analysis and an analysis of convergent validity were performed to document the psychometric properties of the short version. RESULTS: To fit the Rasch model, we reordered thresholds of answering modalities when necessary. Two items were removed. A local dependency between 2 items was solved by combining items modalities into a super-item. A uniform DIF (expected and nonremoved) was identified for one item that was split by joint, and a nonuniform DIF for one item for age and country (removed). The person-item threshold distribution showed a well-focused scale; the confirmatory factor analysis and the analysis of convergent validity showed good fit indicators for the short version. CONCLUSION: The Rasch analysis was helpful in guiding the decision to refine the measurement instrument. After analysis, the 16-item Flare-OA self-report questionnaire is available for use in clinical research.

RESUMEN

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disorder, characterized by progressive heterotopic ossification (HO) and painful soft-tissue inflammatory flare-ups. This was a post-hoc analysis from a phase 2 (NCT03188666) trial in which adults with FOP received intravenous anti-activin A antibody garetosmab 10 mg/kg or placebo every 4 weeks over 28 weeks (Period 1), followed by a 28-week open-label treatment and extension (Period 2 and 3). Here we describe flare-ups, their relationship to new HO lesions, and the impact of garetosmab on flare-ups. Volume of new HO lesions was measured by computed tomography. Patient-reported flare-ups were defined by any two of: new onset of pain, swelling, joint stiffness, decrease in movement, or perceived presence of HO. Flare-ups were experienced by 71% (17/24) of placebo-treated patients, 59% (10/17) of whom developed a new HO lesion irrespective of flare-up location; 24% of flare-ups location-matched new HO lesions. Twenty-nine new HO lesions occurred in the placebo cohort by week 28, of which 12 (41%) occurred in the same location as new or ongoing flare-ups. A higher volume of newly formed heterotopic bone (week 28) occurred in placebo-treated patients who had experienced a prior flare-up versus those without (median [Q1:Q3] of 16.6 [12.0:31.1] cm3 versus 3.2 cm3). Garetosmab was previously shown to decrease patient-reported flare-up frequency in Period 1; here, garetosmab reduced the median (Q1:Q3) duration of patient reported flares (15.0 [6.0:82.0] versus 48.0 [15.0:1.00] days) and severity of flare-ups versus placebo. Frequency of corticosteroid use was numerically reduced in those treated with garetosmab (40.0%) versus placebo (58.3%). In this analysis, 71% of placebo-treated adults with FOP experienced flare-ups over 28 weeks, which were associated with an increased volume of newly formed heterotopic bone. Garetosmab reduced the severity and duration of flare-ups with effects sustained during the entire trial.

---

Fibrodysplasia ossificans progressiva (FOP) is a very rare genetic disorder caused by mutations in ACVR1, a gene that encodes for a receptor. In FOP, the mutated receptor is uniquely activated by activin A, a protein that binds ACVR1 (but does not normally activate it). When FOP-mutant ACVR1 is activated by activin A, this causes new bone to form in places where it does not usually develop. More specifically, in FOP, soft tissues (such as skeletal muscles) and connective tissues (such as tendons and ligaments) are gradually replaced by bone outside of the normal skeleton­a process referred to as heterotopic ossification (HO). In people with FOP, the build-up of bone impacts their mobility. Additionally, people with FOP also experience flare-ups, which are painful swellings of the soft tissues. This analysis investigated flare-up events, the relationship of flare-ups to new HO lesions, and the impact of garetosmab on flare-ups during a clinical trial that enrolled people with FOP. Garetosmab is a monoclonal antibody that binds to activin A and blocks it from activating the faulty receptor, hence stopping new heterotopic bone from forming. In this study, approximately half of the patients randomly received placebo and the other half randomly received garetosmab, the study drug. Of the people who received placebo, 71% experienced flare-ups and 59% percent of those who had flare-ups developed a new HO lesion irrespective of flare-up location. We previously reported that garetosmab decreases patient-reported flare-up frequency. In this study, we show that garetosmab also reduces the duration and severity of flare-ups, as well as the frequency of corticosteroid use with the treatment effect maintained for the entire trial.

RESUMEN

BACKGROUND: Urinary dysfunction is an adverse event of low-dose-rate brachytherapy (LDR-BT) in patients with prostate cancer. We aimed to examine the time to α-1 adrenergic antagonist withdrawal after LDR-BT initiation. METHODS: We retrospectively evaluated 1663 patients who underwent LDR-BT at our hospital during 2004-2022. RESULTS: Overall, 1485/1663 (89.3%) patients were able to stop using α-1 adrenergic antagonists, 1111 (66.8%) of them within 1 year of LDR-BT. Risk factors for prolonged time to withdrawal were age ≥70 years, taking agents for lower urinary tract symptoms prior to LDR-BT, an International Prostate Symptom Score ≥8, an Overactive Bladder Symptom Score ≥3 and a residual urine volume ≥20 ml. Of the patients who were able to stop taking α-1 adrenergic antagonists, 357/1485 (24.0%) required resumption, 218 (61.1%) of whom did so between 1 and 3 years after LDR-BT. This period matched the period of transient worsening of the urinary symptom score. Finally, multivariable analysis identified supplemental external beam radiotherapy and an Overactive Bladder Symptom Score ≥3 as independent risk factors for α-1 adrenergic antagonist resumption. CONCLUSIONS: Withdrawal of α-1 adrenergic antagonists was possible in 66.8% of patients within 1 year of LDR-BT. Our results suggest that patients who are older or have pre-treatment LUTS may have prolonged deterioration of urinary dysfunction after treatment. Resumption of α-1 adrenergic antagonists 1-3 years after treatment may be associated with urinary symptom flares, and close attention is necessary for patients with supplemental external beam radiotherapy and a high pretreatment Overactive Bladder Symptom Score.

RESUMEN

Exacerbations and new onset of immune-mediated inflammatory diseases, such as psoriasis and hidradenitis suppurativa, have been reported following COVID-19 vaccination. In patients with hidradenitis suppurativa, recent studies have shown that those who received mRNA vaccines were 3.5 times as likely to develop flares following vaccination compared to patients who received non-mRNA vaccines, indicating that mRNA COVID-19 vaccines are associated with hidradenitis suppurativa flares. Similar findings have been found in other studies evaluating the association between COVID-19 vaccines and other immune-mediated inflammatory diseases such as psoriasis, atopic dermatitis, lichen planus, and alopecia areata. However, further research is warranted in larger populations to validate these findings.

RESUMEN

When a camera lens is directly faced with a strong light source, image flare commonly occurs, significantly reducing the clarity and texture of the photo and interfering with image processing tasks that rely on visual sensors, such as image segmentation and feature extraction. A novel flare removal network, the Sparse-UFormer neural network, has been developed. The network integrates two core components onto the UFormer architecture: the mixed-scale feed-forward network (MSFN) and top-k sparse attention (TKSA), creating the sparse-transformer module. The MSFN module captures rich multi-scale information, enabling the more effective addressing of flare interference in images. The TKSA module, designed with a sparsity strategy, focuses on key features within the image, thereby significantly enhancing the precision and efficiency of flare removal. Furthermore, in the design of the loss function, besides the conventional flare, background, and reconstruction losses, a structural similarity index loss has been incorporated to ensure the preservation of image details and structure while removing the flare. Ensuring the minimal loss of image information is a fundamental premise for effective image restoration. The proposed method has been demonstrated to achieve state-of-the-art performance on the Flare7K++ test dataset and in challenging real-world scenarios, proving its effectiveness in removing flare artefacts from images.

RESUMEN

Systemic lupus erythematosus (SLE) is an autoimmune disease with a variable course with unpredictable flares. Identifying predictors of these flares is essential for monitoring and timely hospital care. To characterize the prevalence of flares within the first five years of SLE diagnosis and determine the clinical and immunological characteristics associated with flare development among patients attending the Rheumatology Clinic at Tikur Anbesa Specialized Hospital (TASH) and Lancet General Hospital. A multicenter, cross-sectional study was conducted from May 2023 to November 2023 at TASH and Lancet General Hospital. The data was collected from electronic medical records and analyzed using SPSS version 26. Logistic regressions were used to determine factors associated with lupus flare. Most patients with SLE were female (95.4%). The most common clinical presentations were musculoskeletal (71.8%), cutaneous (55%), and constitutional (22%). Almost half (44.3%) of the patients had comorbidity illness. Positive ANA test was found in 96.5% of the patients, whereas only 55% had positive anti-dsDNA test. The prevalence of SLE flare in the first five years of SLE diagnosis was 38.9%, and most flares occurred within the first year of diagnosis. Patients with the following characteristics were more likely to have flare-ups: younger age at diagnosis (less than 25 years old), initial presentation with vasculitis, renal flare, and being on low-dose prednisolone. The most common clinical presentations were musculoskeletal, dermatologic, and constitutional manifestations. Age < 25 years at diagnosis, initial clinical presentation with renal manifestation, and being on low-dose prednisolone were predictors of SLE flare. Key Points • This study found a significant gender disparity, with 95% female. • Nearly 39% of patients experienced an SLE flare within the first five years of diagnosis. • Over three-quarters (77%) of flares occurred within the first year of diagnosis. • Age less than 25 years, initial presentation with vasculitis, renal involvement, and being on low-dose prednisolone were identified as predictors of flares.

Asunto(s)

Lupus Eritematoso Sistémico , Humanos , Femenino , Estudios Transversales , Masculino , Lupus Eritematoso Sistémico/epidemiología , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Adulto , Factores de Riesgo , Estudios Retrospectivos , África del Sur del Sahara/epidemiología , Adulto Joven , Persona de Mediana Edad , Brote de los Síntomas , Prevalencia , Adolescente , Modelos Logísticos

RESUMEN

BACKGROUND: COPD primarily impairs expiratory flow due to progressive airflow obstruction and reduced lung elasticity. Increasing evidence underlines the importance of inspiratory flow as a biomarker for selecting inhaler devices and providing ancillary aerodynamic information. RESEARCH QUESTION: Does the longitudinal changes in maximum forced inspiratory flow (FIFmax) influence acute exacerbations and lung function decline in patients with COPD? STUDY DESIGN AND METHODS: This longitudinal study evaluated FIFmax in patients with COPD over a 7-year period from 2004 to 2020. Eligible patients were categorized into 2 groups based on FIFmax trajectory: the increased FIFmax group and the decreased FIFmax group. The study assessed the annual rate of acute exacerbations and the annual decline rate of FEV1. Subgroup analyses were conducted based on treatment status, with a focus on inhaled therapy and inhaler device usage. RESULTS: Among the eligible 956 patients with COPD, 56.5% belonged to the increased FIFmax group. After propensity score matching, the increased FIFmax group experienced lower rates of severe exacerbations (0.16 per year vs 0.25 per year, P = .017) and a slower decline in FEV1 (0 [interquartile range, -51 to 71] mL/y vs -43 [interquartile range, -119 to 6] mL/y; P < .001) compared with the decreased FIFmax group. These associations were particularly prominent in patients using specific inhaler therapies such as dry powder inhalers. INTERPRETATION: This study showed that the longitudinal changes in FIFmax are associated with clinical outcomes in patients with COPD. Patients with increased FIFmax experienced a lower rate of severe exacerbations and a slower decline in lung function. These findings suggest the potential benefits of optimizing inspiratory flow in COPD management, although further studies are needed to confirm these observations due to potential confounding factors.

RESUMEN

OBJECTIVE: We focused to analyze the time-course changes at pre- and post-flare of T peripheral helper (Tph) cells and circulating T follicular helper (Tfh) cells in the blood of patients with systemic lupus erythematosus (SLE) with lupus low disease activity state (LLDAS) before flare. METHODS: This study included inactive (n = 29) and active (n = 55) patients with SLE. Tph subsets, Tfh subsets, CD11chi B cells, and plasma cells in the blood were determined by flow cytometry. The blood levels of cytokines including interferons (IFNs) were measured by electrochemiluminescence assay or cytokine beads array. RESULTS: Active SLE patients exhibited the increased frequency of Tph1, Tph2, Tfh1, and Tfh2 subsets when compared to inactive patients, but no clear changes in the other subsets. During the treatment with medications, Tph1, Tph2, and Tfh2 subsets were significantly reduced along with disease activity and Tph1 and Tph2 subsets were positively correlated with SLE disease activity index (SLEDAI). The time course analysis of patients at pre- and post-flare revealed that in the patients at LLDAS before flare, Tph subsets and Tfh subsets were relatively low levels. At the flare, Tph cells, particularly Tph1 and Tph2 subsets, were increased and correlated with SLEDAI. Furthermore, the blood levels of IFN-α2a, IFN-γ, and IFN-λ1 were low in the patients with LLDAS before flare but these IFNs, particularly IFN-λ1, were increased along with flare. CONCLUSION: Increased frequency of Tph1 and Tph2 subsets and elevated levels of serum IFN-λ1 are presumably critical for triggering of flare in SLE.

Asunto(s)

Lupus Eritematoso Sistémico , Células T Auxiliares Foliculares , Linfocitos T Colaboradores-Inductores , Humanos , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/sangre , Femenino , Adulto , Masculino , Persona de Mediana Edad , Células T Auxiliares Foliculares/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Colaboradores-Inductores/metabolismo , Estudios Longitudinales , Citocinas/sangre , Citocinas/metabolismo , Biomarcadores/sangre , Índice de Severidad de la Enfermedad , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Adulto Joven

RESUMEN

Tumor flare reaction (TFR) is characterized by an increase in lesion size during immune-based therapy, often resembling disease progression. It signifies inflammation at the tumor site and is frequently seen in immunotherapy, where it is termed "tumor pseudoprogression." The exact mechanisms behind TFR remain unclear. We report the case of a 62-year-old Japanese man with relapsed and refractory diffuse large B cell lymphoma treated with epcoritamab. On day 10 of the first epcoritamab cycle, after two subcutaneous injections of epcoritamab, the cutaneous lymphoma lesions became swollen. This was identified as TFR, and was managed with a three-day course of intravenous dexamethasone at 12 mg/day. The third injection, scheduled for day 15, was delayed by 1 week. Four doses of epcoritamab were completed over the initial 35-day period. A skin biopsy was performed on day 30. Histopathological examination showed CD20+ large atypical lymphocytes forming residual nodules, encircled by CD4+ and CD8+ lymphocytes, with a predominance of CD8+ T cells over CD4+ T cells. Although infrequent, TFR may be a significant indicator of tumor response to epcoritamab therapy. The diagnosis of TFR could be underestimated, and proper identification and understanding of its clinicopathological features are crucial for its effective management.

Asunto(s)

Linfoma de Células B Grandes Difuso , Humanos , Masculino , Persona de Mediana Edad , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/tratamiento farmacológico , Dexametasona/administración & dosificación , Linfocitos T CD8-positivos/inmunología , Progresión de la Enfermedad

RESUMEN

This study aimed to determine the effects of indoor environment (IE) and outdoor air pollutants (OAPs) in residential areas on acute exacerbation (AE) in patients with severe asthma. A total of 115 participants were recruited. To characterize IE, we used structured questionnaires and estimated OAP concentrations using a land-use regression model. Participants who were exposed to passive smoking and lived in houses where the kitchen and living room were not separated showed a significantly higher rate of AE (p = 0.014 and 0.0016, respectively). The mean concentration of PM2.5 in residential areas during the last 3 years was significantly higher in participants with AE than that in those without AE (19.8 ± 3.1 vs. 21.0 ± 2.5 µg/m3, p = 0.033). Moreover, the serum level of 8-hydroxy-2'-deoxyguanosine significantly increased in participants with AE compared to those without AE (56.9 ± 30.0 vs. 94.7 ± 44.5 ng/mL, p = 0.0047) suggesting enhanced oxidative stress in those with AE.

RESUMEN

PURPOSE: To explore if COVID-19 infection and its subsequent immunosuppressant adjustment as well as previous vaccination status are associated with higher risks of uveitis flare in patients with Behcet's disease. METHODS: This retrospective multicenter cohort study was conducted in January 2023 among patients with Behcet's uveitis, during the second wave of the COVID-19 pandemic in China, with an anticipated sample size of 250. The primary objective was to examine the association between COVID-19 infection and the occurrence of uveitis flare. The potential impact of other exposures, including the patient's vaccination status and treatment adjustments to the risk of uveitis flare and the course of COVID-19 infection were also analyzed. RESULTS: 207 patients with COVID-19 infection and 47 patients without COVID-19 infection were included. A total of 127 uveitis flares occurred in the observational period (14.29 events per 100 person-month). COVID-19 infection was found to be significantly associated with a higher rate of uveitis flare (adjusted rate ratio = 4.8, 95% CI 3.7 to 6.3, P < 0.001). However, neither systemic immunosuppressive adjustment nor COVID-19 vaccination status showed a significant association with uveitis flare or the course of COVID-19 infection. CONCLUSIONS: This study provides evidence of an association between COVID-19 infection and an increased risk of uveitis flare in patients with Behcet's disease. However, there was no significant evidence to support that baseline immunosuppressive therapy regimens, treatment adjustment after COVID-19 infection, or vaccination status were associated with higher risks of uveitis flare or prolonged COVID-19 course.

RESUMEN

Lupus nephritis (LN) diagnosis and follow-up requires noninvasive biomarkers. Therefore, the added value of coupling the urinary soluble (s)CD163/creatinuria ratio with serological markers was evaluated in a real-world clinical practice. To this end, a monocentric and retrospective study was conducted in 139 SLE patients with biopsy-proven nephritis having an active LN (LN-A, n = 63 with a positive SLEDAI-renal score) or inactive (n = 76), as well as 98 non-renal SLE patients. The urinary sCD163/creatinuria ratio outperformed serological markers for predicting LN-A (AUC>0.972; p < 10-4 with a 100 % specificity threshold fixed at 320 ng/mmol), and for monitoring renal activity allowing prediction of impending flares and remissions in follow-up (AUC = 0.789, p < 10-4). LN-A patients with an elevated spot proteinuria/creatinuria ratio (p = 8 × 10-6) and sCD163/creatinuria ratio (p = 10-3) were at risk for developing end-stage kidney disease but sCD163/creatinuria ratio cannot substitute kidney biopsy to discriminate LN-A from other glomerulonephritis. Among serological markers (n = 14), anti-dsDNA and anti-C1q antibodies (Abs) (AUC>0.750 versus non-LN patients, and AUC>0.640 versus LN-IR patients) best predicted LN-A, and higher levels were retrieved in class III/IV proliferative LN-A. In multivariate logistic regression analysis, the urinary sCD163/creatinuria ratio remained the only statistically significant biomarker to predict LN-A (p < 0.001). In conclusion, and as compared to classical serological markers, the urinary sCD163/creatinuria ratio provides an additional parameter for monitoring LN patients.