LCN2 as a Potential Diagnostic Biomarker for Ulcerative Colitis-Associated Carcinogenesis Related to Disease Duration

BackgroundPatients with long-duration ulcerative colitis (UC) had a higher risk of developing ulcerative colitis-associated carcinogenesis (UCAC) when compared to those with short-duration UC. This study aimed to discover the biomarker for cancer surveillance related to disease duration.MethodsThe microarrays were divided into short-duration (<10 years) UC, long-duration (≥10 years) UC, UCAC, and normal groups in the Gene Expression Omnibus (GEO) datasets. Differentially expressed genes (DEGs) of GEO and the hub genes of the selected weighted gene co-expression network analysis (WGCNA) were intersected to obtain the overlapping genes. Among these genes, the key gene was identified by using the protein–protein interaction (PPI) network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the cytoHubba of Cytoscape, and the expression levels. Also, immunofluorescence of human colonic mucosa and animal experiment were used to validate the expression trend of the key gene in the progress of UC developing into UCAC.ResultsLipocalin-2 (LCN2) was more relevant with disease duration of UC and significantly negatively correlated with the risk of UCAC. The expression level of LCN2 in short-duration UC was higher than that of long-duration UC (P < 0.01), long-duration UC was higher than that of UCAC (P = 0.001), and UC and UCAC were all higher than that of the normal (P < 0.001). We then discovered that the expression trend of LCN2 in blood and stool samples was consistent with that in colorectal mucosa.ConclusionThe research indicates that LCN2 could be a novel biomarker to evaluate cancer surveillance related to disease duration of developing UC into UCAC. Compared with that of blood samples, stool detection of LCN2 may have more advantages for diagnosis value of early stage of UCAC as a complement to colonoscopy surveillance.

Changes in the Foveal Outer Nuclear Layer of Central Serous Chorioretinopathy Patients Over the Disease Course and Their Response to Photodynamic Therapy

Objective:To investigate the association between foveal outer nuclear layer (ONL) thickness and the natural course of central serous chorioretinopathy (CSC), as well as the thickness change after photodynamic therapy (PDT), exploring the PDT timing for CSC.Methods:This retrospective consecutive case series included 358 CSC patients between January 2014 and December 2019. All patients were divided into four groups depending on disease duration: Group A: ≤1 month; Group B: >1 and ≤3 months; Group C: >3 and≤6 months and Group D: >6 months. Foveal ONL thickness of the CSC eye and the clinically healthy fellow eye were measured and compared in all patients. Fifty-six patients were successfully treated with half-dose of PDT, showing complete subretinal fluid absorption, were followed up for more than 6 months and further investigated. The recovery of foveal ONL thickness was analyzed in the affected eyes of patients with different disease duration.Results:No significant reduction was found in CSC foveal ONL thickness (μm) compared to the fellow eye in patients with disease duration less than 1 week (112.3 ± 12.2 vs. 116.7 ± 15.3, P = 0.268). Patients with longer disease duration had varying degrees of ONL thinning compared to the contralateral eye (all P < 0.05) and this difference was more pronounced in patients with disease duration greater than 6 months (75.8 ± 12.9 vs. 113.0 ± 11.5, P < 0.001). At 6-month follow-up after PDT, foveal ONL thickness of patients with <1 month disease duration recovered significantly from onset (97.3 ± 18.2 to 113.6 ± 8.7, P < 0.001) and became similar to that of the healthy fellow eye. Foveal ONL thickness of patients with duration>1 and≤3 months recovered significantly (88.5 ± 11.5 to 95.8 ± 11.3, P = 0.012) but remained thinner than that of the healthy fellow eye. Foveal ONL thickness did not improve significantly in cases with disease duration longer than 3 months (P > 0.05).Conclusion:Foveal ONL thinning was positively associated with disease duration prior to treatment suggesting that longer disease duration limits scope for foveal ONL recovery. CSC patients should be treated with PDT as soon as possible to prevent disease development and reduced visual function.

Chronic inducible urticaria: Clinical presentation, diagnosis, and management

Chronic inducible urticaria (CIndU) is a subtype of chronic urticaria characterized by recurrent itchy wheals and/or angioedema for more than 6 weeks. CIndU has a longer disease duration than chronic spontaneous urticaria (CSU) and wheals are shorter lasting than CSU. CIndU incudes physical and non-physical urticaria. Triggers and diagnosis of subtypes of CIndU differ from each other. Patient education for avoiding triggers is an important aspect of the treatment of CIndU. There is no significant difference in the treatment approach for CIndU and CSU. In this article, we have discussed different types of CIndU, their clinical features, diagnosis, and management.

Excessive Daytime Sleepiness Is Associated With Non-motor Symptoms of Multiple System Atrophy: A Cross-Sectional Study in China

Objectives: Excessive daytime sleepiness (EDS) in multiple system atrophy (MSA) has received scant attention in the literature, thus the present cross-sectional study aimed to investigate the prevalence of EDS and its potential risk factors among Chinese patients with MSA.Methods: A total of 66 patients with MSA (60.6% males) were consecutively recruited. Eighteen patients (27.3%, 13 men) with Epworth Sleepiness Scale score >10 were defined as having EDS. Demographic, motor [Unified Multiple-System Atrophy (UMSARS)] and non-motor symptoms [Non-Motor Symptoms Scale (NMSS)], and sleep parameters [polysomnography (PSG)] were compared between patients with MSA with and without EDS. A logistic regression analysis was used to calculate the risk factors of EDS in patients with MSA.Results: There were no significant differences in age, sex, MSA onset age, disease duration, MSA sub-type, and motor symptom severity between MSA patients with and without EDS. However, compared with the MSA patients without EDS, their counterparts with EDS had higher scores of NMSS (65.3 ± 23.1 vs. 43.4 ± 25.3, P = .0002), Hamilton Anxiety (HAMA) [15.3 (10.3–20.0) vs. 9.5 (3.0–15.0), P = 0.006], Hamilton Depression (HAMD) [13.7 (12.5–17.8) vs. 9.0 (4.0–13.0), P = 0.015], and Fatigue Severity Scale (FSS) [29.8 (17.3–47.8) vs. 18.7 (10.3–21.8), P = 0.040]. Conversely, the patients with EDS had lower score of Mini-Mental State Examination (MMSE) [23.3 (20.3–27.0) vs. 25.7 (22.0–29.0), P = 0.023]. Similarly, there was a significantly lower percentage of N3 sleep (%) [0.3 (0–0) vs. 2.0 (0–0), P = 0.007] and a higher apnea-hypopnea index (AHI/h) [30.5 (14.5–47.8) vs. 19.3 (5.0–28.7), P = 0.034] in patients with EDS. After adjusting for age, sex, disease duration, MSA sub-type, and UMSARS score, the odds ratio (OR) (95% CI) of EDS was higher while increasing scores in FSS [1.06 (1.02–1.11)], HAMA [1.16 (1.04–1.28)], HAMD [1.13 (1.02–1.25)], NMSS [1.04 (1.01–1.07)], and AHI [1.03 (1.00–1.10)]. The OR of EDS was lower while the MMSE score was increasing [0.85 (0.72–1.00)].Conclusions: The presence and severity of EDS may be significantly associated with the non-motor dysfunction, including fatigue, anxiety, depression, cognitive dysfunction, and sleep-related breathing disorder, but not with the motor dysfunction in MSA.

Correlation Analysis of Surgical Efficacy and Risk Factors of Cervical Spondylotic Myelopathy with High Signal Intensity on MRI-T2WI

Objectives: Objectives: The purpose of this study was to investigate the surgical efficacy and risk factors of cervical spondylotic myelopathy (CSM) patients with increased signal intensity (ISI) on T2-weighted magnetic resonance imaging (MRI-T2WI). Methods: We compared the surgical outcomes of CSM patients with and without ISI. In addition, we compared the efficacy of anterior and posterior cervical decompression in CSM patients with ISI. We also analyzed the risk factors of MRI-T2WI ISI in CSM patients. Results: The incidence of ISI among 153 CSM patients was 71.89%. The JOA score and JOA remission rate were better in the ISI-free than ISI group. The postoperative JOA score and JOA remission rate were better in the posterior than anterior approach surgery group. The disease duration and vertebral canal volume were risk factors for ISI in CSM patients. Conclusion: Among patients with CSM, the prognosis is worse for those with than without ISI. Posterior cervical decompression surgery produces a better curative effect than does anterior cervical decompression surgery in CSM patients with ISI. CSM patients who have a long disease duration and small vertebral canal volume should undergo surgical treatment as early as possible.

Self-perceived quality of sleep among COPD patients in Greece: the SLEPICO study

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide accompanied by a substantial social and economic burden for the patient and the society. Poor sleep quality among COPD patients is frequently unnoticed and unaddressed by physicians and patients themselves, although it is a major source of further deterioration of these patients’ quality of life. The aim of the present study was to record the quality of sleep in COPD patients among the Greek population and correlate these findings with various features of these patients, using the COPD and Asthma Sleep Impact Scale (CASIS). This was a cross-sectional observational study. Forty different variables (demographics, vital sign measurements, COPD-related medical history parameters, comorbidities, CASIS questionnaire results, COPD assessment test, COPD severity based on spirometry measurements, COPD stage based on the ABCD assessment approach, inhaled COPD treatment report) were collected from 3454 nation-wide COPD patients (Greece). The study sample consisted of COPD patients, mainly male (73%) with a median age of 69 years and a median BMI of 27.2. More than half of COPD patients (60.6%) suffered from moderate disease severity and 23.8% from severe disease, while less than half (42.1%) suffered from at least one exacerbation of the disease over the last year prior study enrollment. About 14% reported frequent to very frequent issues affecting their sleep quality, between a fourth and a third of them reported occasional night sleep disturbances, and at least half of them reported no or very infrequent problems in their night sleep. Our study indicates that the COPD assessment test (CAT) and the spirometry-based disease severity can predict the poorness in the quality of sleep (F2,3451 = 1397.5, p < 0.001, adj. R2 = 0.45) as assessed by CASIS score, and that the latter also correlates with age (ρ = 0.122, p < 0.001) and disease duration (ρ = 0.104, p < 0.001). On the contrary, there appears to be no correlation between sleep quality and number of exacerbations. Finally, untreated patients with COPD suffer from poorer quality of sleep compared to treated subjects, independently of the use of inhaled corticosteroids (F2,3451 = 21.65, p < 0.001). The results of the SLEPICO study show that increased age, prolonged disease duration, and especially CAT score ≥ 10, and severe COPD stage, might act as important indicators for deterioration in the quality of sleep, with potential consequences in the daily routine of those patients, thus urging potentially for further pharmacological interventions or modifications.

Nationwide cross-sectional survey of patients with relapsing polychondritis in 2019 demonstrates reduction of airway involvement compared with that in 2009

We conducted retrospective cohort studies of patients with relapsing polychondritis (RP) twice in 2009 and 2019, using a physician questionnaire. We compared the patients’ clinical statuses between the years. Age and gender were comparable between the two surveys. Mean disease duration was longer in 2019 survey (8.3 years) than that in 2009 survey (4.8 years, P < 0.001). The mortality rate declined in 2019 survey compared with those in 2009 survey (from 9.2 to 1.6%, P < 0.001). Incidence of airway involvement decreased in 2019 survey compared with that in 2009 survey (from 49 to 37%, P = 0.012). In 2019 survey, we found more frequent use of biological agents and immunosuppressants in patients with airway involvement. When we focused on RP patients with airway involvement, physicians in 2019 chose methotrexate and calcineurin inhibitors preferentially, compared with azathioprine and cyclophosphamide. Of note is that increased use of infliximab was observed in RP patients with airway involvement, but not in those without. Reduction of airway involvement and mortality in patients with RP was observed in 2019 survey. The reduction may associate with the frequent use of biologics including infliximab in RP patients with airway involvement.

Paramagnetic rim lesions are associated with pathogenic CSF profiles and worse clinical outcomes in multiple sclerosis: a retrospective cross-sectional study

Background and Objective: Paramagnetic rims have been observed as a feature of some MS lesions on susceptibility-sensitive MRI and indicate ongoing inflammation, principally consisting of compartmentalized activated microglia/macrophages. We investigated clinical, MRI, and intrathecal (cerebrospinal fluid, CSF) associations of paramagnetic rim lesions (PRL) using 3T MRI in MS. Methods: This is a retrospective, cross-sectional analysis of patients at a single neuroimmunology clinic. All patients had standardized 3T MRI using a multiecho T2*-weighted sequence with susceptibility postprocessing (SWAN protocol, GE) as part of the inclusion criteria. SWAN-derived filtered phase maps and corresponding T2-FLAIR images were manually reviewed by one expert rater blinded to clinical data, and PRL were determined based on qualitative assessment of hypointense paramagnetic edges on corresponding T2-hyperintense lesions. Descriptive statistics, t-tests, ANOVA, and linear regression determined demographic, clinical, MRI, and intrathecal profile associations with the presence of one or more PRL. Results: One hundred and forty-seven (147) MS patients were included in this analysis (2 clinically isolated syndrome, 118 relapsing-remitting, 14 secondary progressive, 13 primary progressive). Baseline mean age was 48.8 years, disease duration 12.8 years, and median EDSS 2, with 79% women. Seventy-five percent of patients were receiving a disease-modifying therapy, and 79 patients (54%) had available cerebrospinal fluid (CSF) analysis. Sixty-three patients (43%) had at least 1 PRL. PRL status (presence or absence) did not vary by sex or EDSS but was associated with younger age (51 vs 46 years; p=0.01) and shorter disease duration (14.5 vs 10.5 years; p=0.01). PRL status was also associated with worse disease (MS severity score: 2.8 vs 3.7; p=0.05) and blood-brain barrier disruption as determined by higher protein and pathologically elevated albumin quotient, as well as the presence of CSF oligoclonal bands (all p≤0.05); there was no association with immunoglobulin index or synthesis rate. PRL status was additionally associated with higher burden of T2-hyperintense cerebral lesion volume (T2LV), higher age-adjusted cerebral brain volume loss (especially of gray matter), and poorer performance on multiple clinical measures, including the 9-hole peg test and symbol digit modalities test (but not timed 25-foot walk speed). Clinical and intrathecal profiles remained associated with PRL after adjustment for age and in many cases T2LV as well. Sensitivity analyses limited to subgroups of patients without disease activity at the time of CSF sampling remained supportive of results. Patients with PRL were being treated with higher-efficacy disease-modifying therapies at the time of the data query. Conclusions: PRL, an emerging noninvasive biomarker of chronic cerebral neuroinflammation in MS, are confirmed to be associated with greater disease severity and newly shown to be associated with intrathecal inflammation and blood-brain-barrier disruption.

Metabolic syndrome predicts new damage in systemic lupus erythematosus patients: Data from the Almenara Lupus Cohort

Objectives This study aims to determine whether the MetS predicts damage accrual in SLE patients. Methods This longitudinal study was conducted in a cohort of consecutive SLE patients seen since 2012 at one single Peruvian institution. Patients had a baseline visit and then follow-up visits every 6 months. Patients with ≥ 2 visits were included. Evaluations included interview, medical records review, physical examination, and laboratory tests. Damage accrual was ascertained with the SLICC/ACR damage index (SDI) and disease activity with the SLEDAI-2K. Univariable and multivariable Cox-regression survival models were carried out to determine the risk of developing new damage. The multivariable model was adjusted for age at diagnosis; disease duration; socioeconomic status; SLEDAI; baseline SDI; the Charlson Comorbidity Index; daily dose; and time of exposure of prednisone (PDN), antimalarials, and immunosuppressive drugs. Results Two hundred and forty-nine patients were evaluated; 232 of them were women (93.2%). Their mean (SD) age at diagnosis was 35.8 (13.1) years; nearly all patients were Mestizo. Disease duration was 7.4 (6.6) years. The SLEDAI-2K was 5.2 (4.3) and the SDI, 0.9 (1.3). One hundred and eight patients (43.4%) had MetS at baseline. During follow-up, 116 (46.6%) patients accrued at least one new point in the SDI damage index. In multivariable analyses, the presence of MetS was a predictor of the development of new damage (HR: 1.54 (1.05–2.26); p < 0.029). Conclusions The presence of MetS predicts the development of new damage in SLE patients, despite other well-known risk factors for such occurrence.

The Relationship Between Structural Analysis of the Hand and Clinical Characteristics in Psoriatic Arthritis

Background:Up to now, there is only limited information available on a possible relationship between clinical characteristics and the mineralization of metacarpal bones and finger joint space distance (JSD) in patients with psoriasis arthritis (PsA). Computerized digital imaging techniques like digital X-ray radiogrammetry (DXR) and computer-aided joint space analysis (CAJSA) have significantly improved the structural analysis of hand radiographs and facilitate the recognition of radiographic damage. The objective of this study was to evaluate clinical features which potentially influence periarticular mineralization of the metacarpal bones and finger JSD in PsA-patients. Methods:201 patients with PsA underwent computerized measurements of the metacarpal bone mineral density (BMD) with DXR and JSD of all finger joints by CAJSA. DXR-BMD and JSD were compared with clinical features such as age and sex, disease duration, C-reactive protein (CRP) as well as treatment with prednisone and disease-modifying antirheumatic drugs (DMARDs).Results:A longer disease duration and an elevated CRP value were associated with a significant reduction of DXR-BMD, whereas JSD-parameters were not affected by both parameters. DXR-BMD was significantly reduced in the prednisone group (-6.6%), but prednisone showed no impact on finger JSD. Patients under the treatment with bDMARDs presented significant lower DXR-BMD (-9.1%), JSDMCP (-16.8%), and JSDPIP (-12.4%) values. Conclusion:Metacarpal BMD was influenced by inflammatory activity, prednisone use, and DMARDs. In contrast, finger JSD showed only a change compared to baseline therapy. Therefore, metacarpal BMD as well as finger JSD represent radiographic destruction under different aspects.