Could different aqueous humor and plasma cytokine profiles help differentiate between ocular sarcoidosis and ocular tuberculosis?

OBJECTIVE AND DESIGN: A cross-sectional single-center study was conducted to assess cytokine levels in aqueous humor (AH) and plasma of three different uveitis entities: definite ocular sarcoidosis (OS), definite OS associated with QuantiFERON®-TB Gold test positivity (Q + OS) and presumed tubercular uveitis (TBU). SUBJECTS: Thirty-two patients (15 OS, 5 Q + OS, 12 TBU) were included. METHODS: Quantification of selected cytokines was performed on blood and AH samples collected before starting any treatment. Statistical analysis was conducted using the Kruskal-Wallis test, the Mann-Whitney or Fisher test and the Principal Component Analysis (PCA). RESULTS: IL-6, IL-8 and IP-10 levels were higher in AH samples than in peripheral blood. In AH samples, BLC, IL-8 and IP-10 were significantly higher in definite OS than in presumptive TBU. There were no statistically significant differences in terms of cytokine levels between Q + OS and presumptive TBU. PCA showed a similar cytokine pattern in the latter two groups (IFNγ, IL-15, IL-2, IP-10, MIG), while the prevalent expression of BLC, IL-10 and MIP-3 α was seen in definite OS. CONCLUSIONS: The different AH and plasma cytokine profiles observed in OS compared to Q + OS and TBU may help to differentiate OS from TBU in overlapping clinical phenotypes of granulomatous uveitis (Q + OS).

Vogt-Koyanagi-Harada patients show higher frequencies of circulating NKG2Dpos NK and NK T cells.

Vogt-Koyanagi-Harada (VKH) is an autoimmune disease characterized by inflammation in tissues that contain melanocytes. We aimed to increase the knowledge regarding immunological pathways deregulated in VKH disease. We compared the percentages of circulating natural killer (NK), NK T and T cells expressing the activatory markers: CD16, CD69, NK group 2D (NKG2D), natural cytotoxicity triggering receptor 3 (Nkp30), natural cytotoxicity triggering receptor 1 (Nkp46) and the inhibitory marker: NK group 2 member A (NKG2A) in 10 active VKH patients, 20 control subjects (CTR) and seven patients with Behçet disease (BD) by flow cytometry. Cytotoxic potential of NK cells was determined through the degranulation marker CD107a expression after contact with K562 cells by flow cytometry. Moreover, plasmatic levels of 27 cytokines were determined with a multiplex bead-based assay. VKH patients showed higher percentages of NKG2Dpos NK and NK T cells versus CTR. The cytotoxic potential of NK cells induced by K562 cells was comparable between VKH patients and CTR. Finally, higher concentrations of interleukin (IL)-4, IL-5, IL-7, IL-17 and platelet-derived growth factor-subunits B (PDGF-bb) were detected in plasma of VKH patients versus CTR. The immune profile of VKH patients was similar to that of BD patients.

Anterior Segment Optical Coherence Tomography in Uveitis-Glaucoma-Hyphema Syndrome.

PURPOSE: Uveitis-Glaucoma-Hyphema (UGH) syndrome results from contact between the intraocular lens (IOL) and the iris or ciliary body, leading to uveal structure erosion and blood-aqueous barrier breakdown. Treatment involves various drugs, with IOL removal often being necessary. Diagnosis relies on clinical signs, but imaging techniques like ultrasound biomicroscopy (UBM) or anterior segment optical coherence tomography (AS-OCT) are crucial. AS-OCT accurately depicts IOL position and potential contact, emerging as a primary alternative to UBM in the diagnosis. Our study aimed to correlate AS-OCT findings with clinically detectable iris atrophy in pseudophakic patients with IOL-iris chafing and UGH syndrome. METHODS: The study retrospectively analyzed patients diagnosed with UGH syndrome presenting at the Ocular Immunology Unit of Reggio Emilia, Italy, from January 2019 to August 2023. Patients' data were collected. Ophthalmological exams and imaging were performed. The peephole sign in AS-OCT images was evaluated. Statistical analyses were conducted, with a significance level of p ≤ 0.05. RESULTS: The study reviewed 22 eyes of 22 patients with UGH syndrome. Four eyes were excluded, leaving 18 patients (8 females, 10 males). Common misdiagnoses included idiopathic anterior uveitis (55.5%) and herpetic anterior uveitis (16.7%). All patients had iris transillumination defects, mostly focal (77.8%). AS-OCT revealed IOL chafing in all the eyes, with peephole sign correlation. More peephole signs occurred with IOL in the sulcus (p-value = 0.08). CONCLUSION: The study recommends AS-OCT for UGH syndrome confirmation and UBM when IOL-iris chafing is not observed on AS-OCT scans.

Reggio Emilia (Northern Italy) Interdisciplinary Uveitis Clinic: What We Have Learned in the Last 20 Years.

PURPOSE: To analyze the referral patterns and the clinical and therapeutic features of patients diagnosed with uveitis in an Italian tertiary referral center to provide a comparison with previously published series from the same center. METHODS: Retrospective retrieval of data on all new referrals to the Ocular Immunology Unit in Reggio Emilia (Italy) between November 2015 and April 2022 and comparison with previously published series from the same center. RESULTS: Among the 1557 patients, the male-to-female ratio was 1:1.27. Anterior uveitis was the most common diagnosis (53.7%), followed by posterior (21.6%), pan- (18.5%), and intermediate (6.2%) uveitis. The most identifiable specific diagnoses were anterior herpetic uveitis (18.4%), Fuchs uveitis (12.8%), and tuberculosis (6.1%). Infectious etiologies were the most frequent (34.1%) and were more diffuse among non-Caucasian patients (p < 0.001), followed by systemic disease-associated uveitis (26.5%), and ocular-specific conditions (20%). Idiopathic uveitis accounted for 19.4% of cases. Fuchs uveitis presented the longest median diagnostic delay (21 months). Immunosuppressants were administered to 25.2% of patients. Antimetabolites, calcineurin inhibitors, and biologicals were prescribed to 18.4%, 3%, and 11.4% of cases, respectively. Compared to our previous reports, we observed a significant increase in foreign-born patients and in infectious uveitis, a decrease in idiopathic conditions, and an increasing use of non-biological and biological steroid-sparing drugs. CONCLUSIONS: The patterns of uveitis in Italy have been changing over the last 20 years, very likely due to migration flows. Diagnostic improvements and a more widespread interdisciplinary approach could reduce the incidence of idiopathic uveitis as well as diagnostic delay.

Effectiveness of Pegylated Interferon Alpha-2a in Post-Uveitic Macular Edema Previously Responding to Non-Pegylated Interferon.

PURPOSE: To evaluate the efficacy of pegylated interferon (PEG-IFN) alpha-2a to treat post-uveitic relapsing macular edema (ME) after withdrawal of non-PEG IFN alpha-2a or 2b to maintain treatment efficacy. METHODS: This retrospective study investigated subjects with post-uveitic ME who received weekly subcutaneous PEG-IFN alpha-2a injections. Comparisons between baseline central macular thickness (CMT) and best-corrected visual acuity (BCVA) and those at all follow-up visits were made. RESULTS: Six patients (nine eyes) were treated and followed up for six months. CMT (mean [standard deviation]) decreased from 375[117] to 283[39] µm after one month (p < 0.001), remaining significantly lower up to the final follow-up visit at six months (275[38] µm, p = 0.008), and BCVA (0.21[0.16] logMAR at baseline) showed an improvement of 0.12[0.11] logMAR (p = 0.026) at six months. Neither recurrences nor any serious adverse events were recorded. CONCLUSIONS: Post-uveitic ME patients were effectively and safely treated with PEG-IFN alpha-2a.

Epidemiology of Pediatric Uveitis.

Uveitis is uncommon in children and its diagnosis and treatment are challenging. Little is known of the epidemiology of pediatric uveitis. Indeed, population-based studies in the literature are rare. However, there are many tertiary referral center reports that describe the patterns of uveitis in childhood, although few are from developed countries, and their comparison presents some issues. Anterior uveitis is the most frequent entity worldwide, especially in Western countries, where juvenile idiopathic arthritis is diffuse. Most cases of intermediate uveitis do not show any association with infectious or noninfectious systemic diseases. In low- and middle-income countries, posterior uveitis and panuveitis are prevalent due to the higher rates of infectious etiologies and systemic diseases such as Behçet disease and Vogt-Koyanagi-Harada disease. In recent decades, idiopathic uveitis rate has decreased thanks to diagnostic improvements.

Inspiratory Effort and Respiratory Mechanics in Patients with Acute Exacerbation of Idiopathic Pulmonary fibrosis: A Preliminary Matched Control Study.

BACKGROUND: Patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) may experience severe acute respiratory failure, even requiring ventilatory assistance. Physiological data on lung mechanics during these events are lacking. METHODS: Patients with AE-IPF admitted to Respiratory Intensive Care Unit to receive non-invasive ventilation (NIV) were retrospectively analyzed. Esophageal pressure swing (ΔPes) and respiratory mechanics before and after 2 hours of NIV were collected as primary outcome. The correlation between positive end-expiratory pressure (PEEP) levels and changes of in dynamic compliance (dynCRS) and PaO2/FiO2 ratio was assessed. Further, an exploratory comparison with a historical cohort of ARDS patients matched 1:1 by age, sequential organ failure assessment score, body mass index and PaO2/FiO2 level was performed. RESULTS: At baseline, AE-IPF patients presented a high respiratory drive activation with ΔPes = 27 (21-34) cmH2O, respiratory rate (RR) = 34 (30-39) bpm and minute ventilation (VE) = 21 (20-26) L/min. Two hours after NIV application, ΔPes, RR and VE values showed a significant reduction (16 [14-24] cmH2O, p<0.0001, 27 [25-30] bpm, p=0.001, and 18 [17-20] L/min, p=0.003, respectively) while no significant change was found in dynamic transpulmonary pressure, expiratory tidal volume (Vte), dynCRS and dynamic mechanical power. PEEP levels negatively correlated with PaO2/FiO2 ratio and dynCRS (r=-0.67, p=0.03 and r=-0.27, p=0.4, respectively). When compared to AE-IPF, ARDS patients presented lower baseline ΔPes, RR, VE and dynamic mechanical power. Differently from AE-IPF, in ARDS both Vte and dynCRS increased significantly following NIV (p=0.01 and p=0.004 respectively) with PEEP levels directly associated with PaO2/FiO2 ratio and dynCRS (r=0.24, p=0.5 and r=0.65, p=0.04, respectively). CONCLUSIONS: In this study, patients with AE-IPF showed a high inspiratory effort, whose intensity was reduced by NIV application without a significant improvement in respiratory mechanics. In an exploratory analysis, AE-IPF patients showed a different mechanical behavior under spontaneous unassisted and assisted breathing compared with ARDS patients of similar severity.

Prevalence and development of chronic critical illness in acute patients admitted to a respiratory intensive care setting.

INTRODUCTION: Chronic Critical Illness (chronic CI) is a condition associated to patients surviving an episode of acute respiratory failure (ARF). The prevalence and the factors associated with the development of chronic CI in the population admitted to a Respiratory Intensive Care Unit (RICU) have not yet been clarified. METHODS: An observational prospective cohort study was undertaken at the RICU of the University Hospital of Modena (Italy). Patients mechanically ventilated with ARF in RICU were enrolled. Demographics, severity scores (APACHEII, SOFA, SAPSII), and clinical condition (septic shock, pneumonia, ARDS) were recorded on admission. Respiratory mechanics and inflammatory-metabolic blood parameters were measured both on admission and over the first week of stay. All variables were tested as predictors of chronic CI through univariate and multivariate analysis. RESULTS: Chronic CI occurred in 33 out of 100 patients observed. Higher APACHEII, the presence of septic shock, diaphragmatic dysfunction (DD) at sonography, multidrug-resistant (MDR) bacterial infection, the occurrence of a second infection during stay, and a C-reactive protein (CRP) serum level inceasing 7 days over admission were associated with chronic CI. Septic shock was the strongest predictor of chronic CI (AUC = 0.92 p < 0.0001). CONCLUSIONS: Chronic CI is frequent in patients admitted to RICU and mechanically ventilated due to ARF. Infection-related factors seem to play a major role as predictors of this syndrome.

Determination of linuron in water and vegetable samples using stripping voltammetry with a carbon paste electrode.

A carbon paste electrode was used for the electrochemical determination of linuron concentrations in water and vegetable extracts. Optimal conditions were established with respect to electrode activation (electrochemical pretreatment), time accumulation, potential accumulation, scan rate, and pH. The limit of detection achieved with a pre-concentration step was 23.0 µg L(-1). Recovery measurements in vegetable extract and natural water samples were in the range of 98-103%, indicating that the proposed electrochemical method can be employed to analyze linuron in these matrices. The determination results were in good agreement with HPLC results.