Disease Severity Research Articles

The interplay between epidermal barrier distribution, microbiota composition, and immune infiltrate defines and stratifies psoriasis patients and is associated with disease severity

Psoriasis is a chronic inflammatory autoimmune skin disease characterized by keratinocyte hyperproliferation, primarily driven by the IL-23/IL-17 axis. In addition to immune response, various skin components, including the epidermal barrier and the skin microbiota, have been individually implicated in the disease pathogenesis. Here, we aimed to investigate the interplay between epidermal tight junctions, Staphylococcus aureus enterotoxin B (SEB), and CD4 T cell-mediated immune responses. By immunofluorescence analyses of skin biopsies, we observed that claudin-1 distribution was significantly altered in psoriatic patients, which correlated with the localization of Staphylococcus aureus and SEB across skin layers and with disease severity. Furthermore, functional CD4 TCRvβ17 cells were associated with SEB presence in patients skin and positively correlated with psoriasis severity. Notably, in patients with SEB detected in the dermis, CD4 TCRvβ17 IL-17 cells were linked to barrier abnormalities.Unsupervised analysis stratified psoriasis patients into three groups based on SEB presence and location, supporting the previous findings. The patient group with SEB in the dermis exhibited improved responses to biological therapy, including reductions in PASI score, claudin-1 fragmentation, S. aureus and SEB presence, and CD4 TCRvβ17 cell percentages. Our findings emphasize the complex interplay between epidermal barrier distribution, SEB localization, and functional CD4 TCRvβ17 cells in psoriatic skin, highlighting their potential in patient stratification in association with the severity of the disease.

A retrospective analysis on the effectiveness of cytokine hemadsorption in patients with severe coronavirus disease 2019

Background: An increase in systemic inflammation due to hyperimmune activation leads to severe coronavirus disease 2019 (COVID-19) disease, acute respiratory distress syndrome, multiple organ failure, and ultimately death. Extracorporeal blood purification using hemadsorption to reduce excessive inflammatory cytokine was suggested as an effective treatment for patients with severe COVID-19. We investigated the effectiveness of intermittent cytokine hemadsorption with a HA330 cartridge in patients with severe COVID-19. Methods: We gathered data from severe COVID-19 patients who underwent hemadsorption using Jafron® (HA330) between October and December 2021. We assessed pre- and post-hemadsorption inflammatory cytokine levels, treatment complications, and mortality. Statistical significance was set at P < 0.05. Results: Of the total 40 patients, 13 (32.5%) were males with a mean age of 63.6 years. In patients who survived (n = 23), a 2-fold decrease in interleukin-6 (IL-6, P = 0.0433), a 3-fold decrease in procalcitonin (P = 0.0163), a 2.5-fold decrease in C-reactive protein (CRP, P = 0.0080), a 2.5-fold increase in D-dimer (P = 0.0337), and a 1.3-fold increase in white blood cell (WBC) (P = 0.0102) were observed before and after cytokine hemadsorption. In patients who died (n = 17), a 2-fold increase in WBC (P = 0.0022) was observed with no significant changes in other parameters. Except for a few cases of platelet transfusion, catheter occlusion, hypotension, and hematoma, no other complications were observed. A low rate of mortality (33.3%) was observed in patients who received 3 sessions of hemadsorption. Conclusion: Intermittent hemadsorption reduced inflammatory factors and improved outcomes of patients with severe COVID-19. Cytokine hemadsorption can be an effective therapeutic option for establishing inflammatory equilibrium. Our study was a non-comparator and single-center observational study. Larger studies like RCTs are warranted.

Response of Common and Tepary Bean Genotypes to Three Macrophomina phaseolina Isolates Inoculated at Different Growth Stages

Ashy stem blight caused by the fungus Macrophomina phaseolina (Tassi) Goidanich affects Phaseolus spp. in all growth stages. The identification of genotypes with durable resistance is crucial for disease management. The objectives of this research were to determine the following: the aggressiveness of three fungal isolates; the response of common (P. vulgaris L.) and tepary bean (P. acutifolius A. Gray) genotypes at vegetative and midflowering stages; and the presence or absence of SMe1Em5.110 and SS18 molecular markers. Seventeen genotypes were inoculated with the PRI21, PRI22, and PRI23M isolates at the V5 and R2 stages in the greenhouse in Lajas and Isabela. The disease severity was evaluated at 42 days postinoculation. The isolate PRI23M was more aggressive (mean score of 6.2 at V5 and 6.8 at R2) than PRI21 (5.4 and 5.3) in Isabela, whereas there were no significant differences between PRI21 (5.5 and 4.2) and PRI22 (5.0 and 4.3) in Lajas. Tepary bean PI 462025 was intermediate (3.6 to 6.5) to the three isolates, whereas BAT477 and SEA 5 common beans were intermediate to PRI21 and PRI22 and susceptible (scores >6.5) to PRI23M at both growth stages. Likewise, ‘Bella’, ‘Beníquez’, and ‘Verano’ were susceptible to PRI21 and PRI23M at V5 and R2 stages in Isabela. Neither of these genotypes amplified for the two molecular markers. In contrast, NY6020-4 with the SS18 marker was intermediate to PRI21 and PRI22 at the R2 stage in Isabela and Lajas. Moreover, UPR-Mp-22 with the SMe1Em5.110 and SS18 markers was resistant (<3.6) to PRI21 at the V5 stage in both locations and at R2 in Isabela. Two inoculations of M. phaseolina isolates are recommended to identify genotypes with resistance throughout the growing season.

Visual assessments of 11 C-Pittsburgh compound-B PET vs. 18 F-flutemetamol PET across the age spectrum.

Visual assessments of amyloid-β PET, used for Alzheimer's disease (AD) diagnosis and treatment evaluation, require a careful approach when different PET ligands are utilized. Because the gray matter (GM) and white matter (WM) ligand bindings vary with age, the objective was to investigate the agreement between visual reads of 11 C- and 18 F-PET scans. Cognitively unimpaired (CU) younger adults ( N = 30; 39.5 ± 6.0 years), CU older adults ( N = 30; 68.6 ± 5.9 years), and adults with AD ( N = 22; 67.0 ± 8.5 years) underwent brain MRI, 11 C-Pittsburgh compound-B (PiB)-PET, and 18 F-flutemetamol-PET. Amyloid-β deposition was assessed visually by two nuclear medicine specialists on 11 C-PiB-PET and 18 F-flutemetamol-PET, and quantitatively by PET centiloids. Seventy-two 11 C-PiB-PET and 18 F-flutemetamol-PET visual reads were concordant. However, 1 18 F-flutemetamol-PET and 9 11 C-PiB-PET were discordant with quantitative values. In four additional cases, while 11 C-PiB-PET and 18 F-flutemetamol-PET visual reads were concordant, they were discordant with quantitative values. Disagreements in CU younger adults were only with 11 C-PiB-PET visual reads. The remaining disagreements were with CU older adults. Age, GM/WM binding, amyloid-β load, and disease severity may affect visual assessments of PET ligands. Increase in WM binding with age causes a loss of contrast between GM and WM on 11 C-PiB-PET, particularly in CU younger adults, leading to false positivity. In CU older adults, increased WM signal may bleed more into cortical regions, hiding subtle cortical uptake, especially with 18 F-flutemetamol, whereas 11 C-PiB can detect true regional positivity. Understanding these differences will improve patient care and treatment evaluation in clinic and clinical trials.

First real-life data on COVID-19 vaccine effectiveness against hospitalisation and severe disease from the eastern part of the WHO European Region

First real-life data on COVID-19 vaccine effectiveness against hospitalisation and severe disease from the eastern part of the WHO European Region

Robot-Assisted Laparoscopic Adrenalectomy: Extended Application in Children

Minimally invasive surgery for paediatric adrenal tumours has evolved, but robot-assisted laparoscopic adrenalectomy (RALA) in children remains poorly studied. The current prospective study aims to demonstrate the safety and efficacy of RALA in treating children with adrenal tumours. A prospective institutional analysis of children presenting with neuroblastic and endocrine tumours treated with RALA was undertaken over a six year-period. For each child, clinical parameters were collected relating to diagnosis, surgery and outcomes. A total 50 RALA were performed; 23 for unilateral neuroblastic tumours (87% neuroblastomas) and 27 for endocrine tumours. Eight neuroblastic tumours (35%) had image-defined risk factors (all due to tumour invading the renal pedicle). Median length of stay was two days. Resection margins were macroscopically clear in all cases. After median follow-up of 2.9 years (1.6-3.9), two children are under treatment for metastatic relapse (high-risk disease) and three died due to refractory disease. Sixteen children had endocrine tumours: pheochromocytoma (n=13), or bilateral nodular adrenocortical hyperplasia with Cushing's syndrome (n=14). One child required non-emergent conversion, and one complication occurred (grade IIIb) after median follow-up of 3.3 years (1.0-5.7). The current study is the largest reported experience in the literature and confirms the safety and effectiveness of RALA in carefully selected children with adrenal tumours. Through an iterative process and in the setting of a dedicated paediatric robotic surgical team indications have been clarified and extended. The current study confirms RALA has particularly utility in patients with severe disease (IDRF+metastatic neuroblastomas) or genetic predisposition syndromes.

Effects of Psychological Stress on Multiple Sclerosis via HPA Axis-mediated Modulation of Natural Killer T Cell Activity.

The involvement of psychological stress and Natural Killer T (NKT) cells in the pathophysiology of multiple sclerosis has been identified in the progression of this disease. Psychological stress can impact disease occurrence, relapse, and severity through its effects on the Hypothalamic- Pituitary-Adrenal (HPA) axis and immune responses. NKT cells are believed to play a pivotal role in the pathogenesis of multiple sclerosis, with recent evidence suggesting their distinct functional alterations following activation of the HPA axis under conditions of psychological stress. This review summarizes the associations between psychological stress, NKT cells, and multiple sclerosis while discussing the potential mechanism for how NKT cells mediate the effects of psychological stress on this disease.

New Insights on Mechanisms and Therapeutic Targets of Cerebral Edema.

Cerebral Edema (CE) is the final common pathway of brain death. In severe neurological disease, neuronal cell damage first contributes to tissue edema, and then Increased Intracranial Pressure (ICP) occurs, which results in diminishing cerebral perfusion pressure. In turn, anoxic brain injury brought on by decreased cerebral perfusion pressure eventually results in neuronal cell impairment, creating a vicious cycle. Traditionally, CE is understood to be tightly linked to elevated ICP, which ultimately generates cerebral hernia and is therefore regarded as a risk factor for mortality. Intracranial hypertension and brain edema are two serious neurological disorders that are commonly treated with mannitol. However, mannitol usage should be monitored since inappropriate utilization of the substance could conversely have negative effects on CE patients. CE is thought to be related to bloodbrain barrier dysfunction. Nonetheless, a fluid clearance mechanism called the glial-lymphatic or glymphatic system was updated. This pathway facilitates the transport of cerebrospinal fluid (CSF) into the brain along arterial perivascular spaces and later into the brain interstitium. After removing solutes from the neuropil into meningeal and cervical lymphatic drainage arteries, the route then directs flows into the venous perivascular and perineuronal regions. Remarkably, the dual function of the glymphatic system was observed to protect the brain from further exacerbated damage. From our point of view, future studies ought to concentrate on the management of CE based on numerous targets of the updated glymphatic system. Further clinical trials are encouraged to apply these agents to the clinic as soon as possible.

WE-DeepLabV3+: A lightweight segmentation model for Panax notoginseng leaf diseases

Panax notoginseng plays an important role in traditional Chinese medicine. However, diseases pose a significant threat to the quality and yield of P. notoginseng. The main challenge related to the identification of P. notoginseng leaf diseases is how to achieve good performance in the case of small diseased spots on P. notoginseng leaf, overlapping edges of diseased leaf and the difficulty in mobile deployment. A lightweight semantic segmentation model Window Efficient-DeepLabv3+ is proposed for segmentation and quantification of P. notoginseng leaf diseases. We propose the Window Attention-ASPP module and present a hierarchical stacking of features, which improves model accuracy for minor target lesions while reducing parameters. In addition, a lightweight backbone network MobileNetV2 is utilized as a feature extraction module. The decoding stage introduces the Efficient Channel Attention module, which effectively improves the accuracy of the segmentation of the blade contour. Experimental results yielded the Mean Intersection Over Union, Mean Precision, and Mean Recall metrics of WE-DeepLabV3+ network to be 82.0 %, 87.6 %, and 92.4 % respectively, outperforming other segmentation models such as UNet, PSPNet, CaraNet, SegNet, and BiSeNetV2. Moreover, the number of parameters has been reduced by 90.6 % with only 5.1 M parameters. Finally, the method is used to quantify the disease of P. notoginseng leaf, the error is only 1.15 % and 0.82 %, which proves that it can quantify the disease severity accurately. Thus, the proposed method holds great significance for raising the yield and quality of P. notoginseng, also providing reliable guidance for precise fertilization and drug control.

Chitosan-coated nanoemulsions of a terpene-based natural deep eutectic solvent and lemongrass essential oil to control coffee leaf rust: Two alternatives based on natural products

Coffee production is negatively affected by coffee leaf rust, a disease caused by the fungus Hemileia vastatrix. As a natural product-based alternative to chemically control the disease, this study evaluated the effect of two chitosan-coated nanoemulsions prepared from Cymbopogon citratus essential oil (EO) and the thymol: pyruvic acid (1:1) natural deep eutectic solvent (NADES) on the in vitro germination of H. vastatrix urediospores and on the in vivo control of the disease in Coffea arabica plants under greenhouse conditions. Both nanoformulations inhibited urediospores in vitro germination but only that prepared with EO did it significantly more than its free form active ingredient (the observed reduction was around 60 %). On the other hand, the in vivo experiment showed that the EO and NADES chitosan-coated nanoemulsions offered similar and significant protection for Coffea arabica plants against leaf rust; the disease severity level was found to be less than 2.6 % after 81 days from the application of the treatments to the plants (comparable to the cooper oxychloride, which is one of the commercial fungicides traditionally used), while the free components did not (9.0–13.3 % of severity level by day 81, such as the control). This is the first report demonstrating that chitosan-coated nanoemulsions, containing NADES or EO, protect coffee plants against H. vastatrix infection and can be two alternatives for sustainable pest management. Furthermore, this study contributes to broadening the prospects for using hydrophobic NADES in the design of biopesticides.

Disease Progression of GNE Myopathy and Its Relationship With Genotype: A Retrospective, Observational Study in Chinese Patients.

Studies on the natural disease progression of detailed motor dysfunction in patients with GNE myopathy are rare. This study aimed to investigate motor function involvement during disease progression and its relationship with the genotype among Chinese patients with GNE myopathy. This retrospective observational cohort study included all patients with genetically confirmed GNE myopathy enrolled at Peking University First Hospital between 2000 and 2023. Patients with GNE myopathy were stratified into 2 subgroups based on with or without p.D207V mutation. Data on clinically significant muscular problems were collected from patients' medical history and follow-up assessments to evaluate motor function using the GNE Myopathy Functional Activity Scale and the modified Rankin Scale. Eighty-three patients with GNE myopathy were included, with a median age at examination of 36 years (range 25-57) and a median age at onset (AAO) of 26 years (range 16-46). The Kaplan-Meier curves revealed that patients with the p.D207V mutation experienced a significantly later AAO (27 years [95% CI 25-29]) and onset age of wheelchair dependency (50 years [95% CI 46-54]) compared with those without the mutation, who had an AAO of 24 years (95% CI 22-26) and an onset age of wheelchair dependency of 45 years (95% CI 36-54). Multivariate Cox regression analysis, adjusted for sex and disease duration, revealed that patients without the p.D207V mutation had a higher risk of wheelchair dependency, with an adjusted hazard ratio of 2.361 (95% CI 1.030-5.411). Barthel indexes (BIs) were negatively correlated with the disease duration and positively correlated with AAOs. Patients with GNE with earlier AAO exhibited a shorter disease duration of developing functional dependency (BIs <60) than did those with later AAOs. Our results provide insights into the motor function involvement observed during disease progression in Chinese patients with GNE myopathy, and relatively mild disease severity was observed in those with the p.D207V mutation.

Reduced Serum Brain-Derived Neurotrophic Factor in Infants Affected by Severe Bronchiolitis.

Bronchiolitis is an acute viral infection of the lower respiratory tract, typical of infants in their first year of life and causing hypoxia in the most serious cases. Bronchiolitis recognizes various demographic risk factors that are associated with greater clinical severity; however, no laboratory factors are yet able to correlate with the clinical severity. Neurotrophins as Brain-Derived Neurotrophic Factor (BDNF) are mediators of neuronal plasticity. BDNF is constitutively expressed in smooth muscle cells and epithelium of the lower respiratory tract, and as it is released during inflammatory conditions, serum levels may have a relevant role in the prognosis of infants with bronchiolitis. In the present pilot study, we aimed to disclose the presence of serum BDNF in infants hospitalized with bronchiolitis at discharge as a disease severity indicator. Serum BDNF, measured at hospital discharge, was significantly lower in severe bronchiolitis (expressed as O2-supplemented infants). Furthermore, no changes were disclosed for the Tropomyosin receptor kinase B, the main BDNF receptor and neurofilament light chain, a biomarker of neuronal degeneration. Low serum BDNF in infants with severe bronchiolitis could be associated with a higher utilization by lung cells or with an altered production by lung cells. Therefore, further research is required to study if a decreased production or increased consumption of this biomarker is at the base of the above-mentioned findings.

The Effect of Telerehabilitation-Based Self-Management Programme on Individuals With Scleroderma.

Our study endeavoured to develop an online self-management programme facilitated by an interdisciplinary team and to assess its impact on the quality of life, sleep patterns, pain perception, and fatigue levels among individuals diagnosed with scleroderma. Twenty-nine individuals with scleroderma completed the programme. The study spanned 8weeks during which participants received weekly 45-min video sessions. Assessment tools included the Scleroderma Health Assessment Questionnaire (SHAQ) for disease severity and pain intensity, the Self-Efficacy Scale for Chronic Disease Patients for self-management evaluation, the Pittsburgh Sleep Quality Index (PSQI) for assessing sleep quality, the Fatigue Severity Scale for measuring fatigue severity, and the Short Form-12 Quality of Life Scale (SF-12) for evaluating quality of life. Self-management score increased significantly, while fatigue score decreased significantly. Feedback from participants indicated a positive perception of the programme and its content, suggesting its usefulness in managing their condition. Feedback from participants indicated a positive perception of the programme and its content, suggesting its usefulness in managing their condition. The self-management programme, developed collaboratively by an interdisciplinary team and implemented via telerehabilitation, yielded beneficial outcomes concerning self-management skills and fatigue severity among individuals with scleroderma. Strengthening the interdisciplinary composition of the study team by incorporating diverse healthcare professionals may enhance future investigations. Additionally, we advocate for the repetition of the study employing randomised methodologies and implementing long-term follow-up assessments to further elucidate the programme's efficacy and sustainability over time.

Disentangling Neurodegeneration From Aging in Multiple Sclerosis Using Deep Learning: The Brain-Predicted Disease Duration Gap.

Disentangling brain aging from disease-related neurodegeneration in patients with multiple sclerosis (PwMS) is increasingly topical. The brain-age paradigm offers a window into this problem but may miss disease-specific effects. In this study, we investigated whether a disease-specific model might complement the brain-age gap (BAG) by capturing aspects unique to MS. In this retrospective study, we collected 3D T1-weighted brain MRI scans of PwMS to build (1) a cross-sectional multicentric cohort for age and disease duration (DD) modeling and (2) a longitudinal single-center cohort of patients with early MS as a clinical use case. We trained and evaluated a 3D DenseNet architecture to predict DD from minimally preprocessed images while age predictions were obtained with the DeepBrainNet model. The brain-predicted DD gap (the difference between predicted and actual duration) was proposed as a DD-adjusted global measure of MS-specific brain damage. Model predictions were scrutinized to assess the influence of lesions and brain volumes while the DD gap was biologically and clinically validated within a linear model framework assessing its relationship with BAG and physical disability measured with the Expanded Disability Status Scale (EDSS). We gathered MRI scans of 4,392 PwMS (69.7% female, age: 42.8 ± 10.6 years, DD: 11.4 ± 9.3 years) from 15 centers while the early MS cohort included 749 sessions from 252 patients (64.7% female, age: 34.5 ± 8.3 years, DD: 0.7 ± 1.2 years). Our model predicted DD better than chance (mean absolute error = 5.63 years, R2 = 0.34) and was nearly orthogonal to the brain-age model (correlation between DD and BAGs: r = 0.06 [0.00-0.13], p = 0.07). Predictions were influenced by distributed variations in brain volume and, unlike brain-predicted age, were sensitive to MS lesions (difference between unfilled and filled scans: 0.55 years [0.51-0.59], p < 0.001). DD gap significantly explained EDSS changes (B = 0.060 [0.038-0.082], p < 0.001), adding to BAG (ΔR2 = 0.012, p < 0.001). Longitudinally, increasing DD gap was associated with greater annualized EDSS change (r = 0.50 [0.39-0.60], p < 0.001), with an incremental contribution in explaining disability worsening compared with changes in BAG alone (ΔR2 = 0.064, p < 0.001). The brain-predicted DD gap is sensitive to MS-related lesions and brain atrophy, adds to the brain-age paradigm in explaining physical disability both cross-sectionally and longitudinally, and may be used as an MS-specific biomarker of disease severity and progression.

Predictors of Mortality and Neurological Complications in a Large Cohort of Patients With COVID-19

Objectives: This study aimed to investigate the association between the baseline clinical and laboratory characteristics of patients with COVID-19 and their risk of subsequent development of neurological complications and mortality. Methods: This retrospective, single-center cohort study included patients with COVID-19 who presented to the Emergency Department of Razi Hospital. Patients’ charts were reviewed to collect baseline clinical and laboratory data. Results: Of 2205 patients with COVID-19, 1473 (66.8%) developed various neurological complications in addition to other symptoms. Among the 168 patients who died, 66.66%, 43.5%, and 25% had a history of neurological disorders, encephalopathy, and stroke, respectively. Disease severity was significantly associated with comorbidities, hypoxemia, hypoalbuminemia, hypophosphatemia, elevated ESR, hypomagnesemia, stroke, and encephalopathy (P&lt;0.05). The risk of death remained strongly linked to older age, comorbidities, severe infection, ICU admission, and extended hospitalization (P&lt;0.05), even after adjustments, indicating they are potential confounders for other variables. More importantly, in non–critically ill patients, there was no significant association between the risk of death and hypoxemia, anemia, thrombocytopenia, hypomagnesemia, stroke, and encephalopathy (P&gt;0.05). Moreover, the association between encephalopathy and other factors was greatly influenced by disease severity. Nonetheless, older age, comorbidities, and anemia remained significant predictors of stroke even after adjusting for confounders (P&lt;0.05). Conclusions: The high rates of neurological disorders among deceased patients with COVID-19 underscores the need for early prediction and management of these complications. Moreover, neurological disorders were linked to an increased risk of death because they tend to be present in critically ill patients admitted to the ICU with extended hospitalization.

Demographics and Disease Characteristics of Patients with Alopecia Areata with Comorbid Atopic Dermatitis, Vitiligo or Anxiety/Depression: TARGET-DERM AA

Introduction Alopecia areata (AA) is a chronic autoimmune disease. Common AA comorbidities include atopic dermatitis (AD), vitiligo, anxiety and depression (AnxDep). TARGET-DERM AA is an ongoing longitudinal, real-world study of United States and Canadian AA patients. The purpose of this analysis is to assess characteristics among AA patients with and without the above comorbidities. Methods At enrollment (December 2021-June 2024), patients reported outcomes (including comorbidities, Patient Global Impression of Severity-AA, and clinician-reported outcome measures: Severity of Alopecia Tool, Measure for Eyebrow/Eyelash Hair Loss). Characteristics were compared across subgroups. Results Of the 267 AA patients with completed patient questionnaires at enrollment, 61.4% were female; 24.4% were aged &lt;12 years, 13.7% 12-17, and 61.7% 18 or older. Overall, 21.0% self-reported an AD diagnosis (19.7% of pediatric, 11.1% of adolescent, and 25.4% of adult AA patients), 7.1% vitiligo (7.0% of pediatric, 3.7% of adolescent, and 8.5% of adult AA patients) and 44.9% AnxDep (21.1% of pediatric, 40.7% of adolescent, and 58.5% of adult AA patients). 42.1% of patients with comorbid vitiligo had severe AA disease (SALT&gt;50) and 27.8% patients without comorbid vitiligo had SALT&gt;50. 28.6% of those with comorbid AD had SALT&gt;50 compared to 28.9% of those not reporting AD, with 30.0% of AnxDep and 27.9% of non-AnxDep having SALT&gt;50, all p&gt;0.2. 42.1% of patients with comorbid vitiligo reported PGIS-AA ‘severe/very severe’ disease, with 41.1% of patients with comorbid AD and 42.5% of patients with comorbid AnxDep reporting severe/very severe AA disease, all numerically higher than patients without comorbid vitiligo (36.3%), AD (35.6%), and AnxDep (31.9%), all p&gt;.07. Among those with and without vitiligo, 42.1% vs 37.9% had eyebrow involvement, 36.8% vs 30.2% eyelash; considering AD, 35.7% vs 38.9% had eyebrow involvement, 28.6% vs 31.3% eyelash; for AnxDep 39.2% vs 37.4% had eyebrow involvement, 30.8% v 30.6% eyelash, all p&gt;0.5. Discussion In this real-world cohort of AA patients, the presence of specific comorbidities was not associated with statistically significant differences in clinician reported AA severity, eyebrow or eyelash involvement. Comorbid AnxDep was associated with increased patient-reported AA disease severity. Additional research characterizing how dermatologic and psychiatric comorbidities impact health-related quality of life and patient burden has the potential to inform management decisions.

Chronic treatment with SGLT-2 inhibitors is associated with ICU admission and disease severity in patients with diabetic ketoacidosis: a propensity score–matched cohort study

Chronic treatment with SGLT-2 inhibitors is associated with ICU admission and disease severity in patients with diabetic ketoacidosis: a propensity score–matched cohort study

Real-world clinical outcomes and rationale for initiating abatacept as a first-line biologic for patients with anticitrullinated protein antibody- and rheumatoid factor-positive rheumatoid arthritis

Aim: In rheumatoid arthritis (RA), seropositivity for both anticitrullinated protein antibody (ACPA) and rheumatoid factor (RF) is associated with disease severity and therapeutic response. Biologic (b) disease-modifying antirheumatic drugs (DMARDs) such as abatacept are recommended after inadequate response or contraindication to conventional synthetic DMARDs. This retrospective cohort study aimed to describe changes in Clinical Disease Activity Index (CDAI) measures over 12 months among patients with ACPA+ and RF+ RA with an inadequate response to methotrexate treated with abatacept as a first-line bDMARD. Patients &amp; methods: Patient data were abstracted from medical records by treating rheumatologists. Analyses included McNemar tests for paired proportions or paired t -tests to assess longitudinal changes in CDAI scores, and Kaplan–Meier methods for time-to-event outcomes. Serious AEs and rationale for initiating treatment were recorded. Results: Overall, 296 patients were included. Mean CDAI scores improved (decreased) by 34.0, 61.0 and 74.0% (all p &lt; 0.001) from baseline to 3–6 months, 6–12 months and ≥12 months after abatacept initiation, respectively. Of 279 patients not in CDAI low disease activity (LDA) or remission at baseline, 24.7% of patients achieved it within 6 months, 56.3% within 12 months and 71.0% at any point during follow-up after abatacept initiation. Median time to CDAI LDA/remission was 10.2 months. Serious AEs were reported in 2.4% of patients. Common reasons reported by rheumatologists for initiating abatacept were effectiveness/efficacy (52.7%), safety (31.4%) and patient preference (25.3%). Conclusion: In this analysis of patients with ACPA+ and RF+ RA treated with abatacept as a first-line bDMARD in a clinical practice setting, clinical outcomes and remission rates were improved at all time points, providing real-world evidence to further support the use of abatacept in this patient population.

Bimekizumab Efficacy and Safety in Patients With Psoriatic Arthritis Who Had Skin and Nail Psoriasis at Baseline: Up to 2-year Results From Two Phase 3 Studies

Introduction: Bimekizumab (BKZ), a humanized anti-IL17F anti-IL17A antibody has demonstrated efficacy and tolerability to 1 year in patients with psoriatic arthritis (PsA) and psoriasis.1 Nail psoriasis is associated with increased PsA risk, more severe disease and decreased quality of life, in patients with psoriasis.2,3 Here, efficacy and safety of BKZ treatment are reported to 2 years in patients with PsA, skin involvement and nail psoriasis in two phase 3 trials. Methods: BE OPTIMAL (NCT03895203; bDMARD-naïve) and BE COMPLETE (NCT03896581; TNFi‑IR) assessed subcutaneous BKZ 160 mg Q4W in patients with PsA. Placebo (PBO) patients switched to BKZ (PBO/BKZ) at Wk16. BE OPTIMAL included a reference arm (adalimumab [ADA] 40 mg Q2W); ADA patients switched to BKZ at Wk52 (ADA/BKZ). BE OPTIMAL Wk52 and BE COMPLETE Wk16 completers could enter BE VITAL (open-label extension; NCT04009499), where all patients received BKZ. Post-hoc data reported for patients with baseline skin involvement (≥3% body surface area) and nail psoriasis (modified Nail Psoriasis Severity Index &gt;0). Efficacy reported to Wk104 of BE OPTIMAL/Wk100 of BE COMPLETE. Missing data imputed using non‑responder, multiple or worst-category imputation. Safety data are reported for all patients treated with BKZ. Results: Of 263/852 (30.9%) bDMARD-naïve and 159/400 (39.8%) TNFi-IR patients with baseline skin and nail psoriasis, 230 (87.5%) and 136 (85.5%) patients completed Wk104/Wk100. Efficacy responses at Wk52 on BKZ were sustained to Wk104/Wk100 across joint, skin, nail, physical function and composite outcomes. ADA/BKZ cohort showed sustained responses after switch. For bDMARD-naïve and TNFi-IR patients on BKZ, the exposure-adjusted incidence rates per 100 patient-years (EAIR/100 PY) for ≥1 treatment-emergent adverse event (TEAE) were 154.9 and 78.8, respectively; and for serious TEAEs, 6.6 and 5.2 respectively. None of the reported Candida infections were serious or systemic; all 3 deaths were deemed unrelated to treatment. Conclusions: BKZ treatment demonstrated sustained clinical efficacy to 2 years in patients with PsA, skin involvement and nail psoriasis, regardless of prior TNFi treatment. BKZ was well tolerated; consistent safety profile to previous reports.1

Choroidal vascularity index in health and systemic diseases: a systematic review

Abstract Background The choroid, a highly vascular structure within the eye, is significantly influenced by various systemic conditions. The advent of enhanced depth optical coherence tomography has improved our ability to evaluate choroidal pathophysiology. The choroidal vascularity index (CVI), a noninvasive and reliable tool, serves as an effective means of assessing the choroidal vascular structure. Recent studies have increasingly focused on exploring CVI alterations under different systemic conditions. This study aims to provide a comprehensive summary of the latest research findings in this area. Methods A systematic literature review was conducted on October 1, 2023, using two databases, MEDLINE (via PubMed) and Scopus. Search terms were tailored specifically for each database to ensure a thorough exploration of relevant literature. The studies identified were qualitatively assessed, with particular emphasis on outcomes related to CVI and choroidal thickness. Results A total of 48 studies were included in the review, encompassing a diverse range of systemic conditions such as diabetes, central nervous system disorders, cardiovascular diseases, autoimmune disorders, and infectious diseases. Notable reductions in CVI were observed in diabetic retinopathy, autoimmune diseases, and neurodegenerative disorders. Additionally, the review highlighted variations in CVI values related to the severity of systemic diseases, indicating its potential use as a biomarker for disease progression. Conclusion This review highlights the significant correlation between variations in the choroidal vascularity index and diverse systemic conditions affecting hemodynamics. An enhanced understanding of CVI provides deeper insights into the pathophysiological mechanisms underlying these disorders and positions CVI as a promising biomarker for early detection and monitoring. Nevertheless, its clinical utility warrants careful assessment. Future research should address the potential limitations of CVI to fully capitalize on its diagnostic and prognostic potential.