Paradoxical and bimodal immune-mediated dermatological side effects of TNF-α inhibitors: A comprehensive review.

INTRODUCTION: Due to the increasing prevalence of immune-mediated diseases such as psoriasis, lichen planus, rheumatoid arthritis and inflammatory bowel disease, dermatologists have turned to new biologic drugs known as DMARDs (disease-modifying anti-rheumatic drugs) in recent years. AREAS COVERED: In this study, we evaluate the immune-mediated dermatological side effects of DMARDS by reviewing and analyzing previous peer-reviewed research on the effects of TNF-α inhibitors in the treatment of skin diseases, as well as adverse effects of these drugs and some of the main causes of these effects. EXPERT OPINION: DMARDs are very effective in improving control of the above diseases. TNF-α inhibitors are an important group of DMARDs that are widely used. The paradoxical adverse events (PAEs) associated with the use of TNF-α inhibitors are divided into three categories: true paradoxical, borderline paradoxical, and non-paradoxical. True PAEs include conditions for which TNF-α inhibitors are approved for treatment. Borderline PAEs are considered to occur with this class of drugs for which there is no definite approval but for which there is sufficient evidence. Although these events are rare, early recognition of the accused drug and appropriate decision-making may prevent progression of complications and irreversible side effects.

Fluorescein versus Indocyanine Green Angiography Guided Half-Dose Photodynamic Therapy for Chronic Central Serous Chorioretinopathy.

Purpose: To compare the outcomes of fluorescein angiography (FA)-guided and indocyanine green angiography (ICGA)-guided half-dose photodynamic therapy (PDT) in patients with chronic central serous chorioretinopathy (CSC). Methods: In this retrospective comparative study, medical records of eyes with chronic CSC who underwent half-dose PDT were reviewed. A retina specialist performed FA-guided half-dose PDT, and the other performed ICGA-guided treatment. The success of applying PDT in the resolution of subretinal fluid was compared between the FA- and ICGA-guided methods. Results: Eighty-two eyes of 73 patients (41 eyes in each group) received half-dose PDT. After half-dose PDT, a significant improvement in the best-corrected visual acuity (BCVA) was found at the time of the last follow-up in both groups (both P < 0.001), with no significant intergroup difference. Central subfield and subfoveal choroidal thicknesses decreased significantly in both groups at the last follow-up (all P < 0.05), with no significant differences between the groups. Subretinal fluid (SRF) resolved in all eyes, and no persistent SRF was detected during the follow-up period. Conclusion: FA-guided and ICG-guided half-dose PDT may have similar efficacy for the treatment of chronic CSC.

Glioma Tumor Grading Using Radiomics on Conventional MRI: A Comparative Study of WHO 2021 and WHO 2016 Classification of Central Nervous Tumors.

BACKGROUND: Glioma grading transformed in World Health Organization (WHO) 2021 CNS tumor classification, integrating molecular markers. However, the impact of this change on radiomics-based machine learning (ML) classifiers remains unexplored. PURPOSE: To assess the performance of ML in classifying glioma tumor grades based on various WHO criteria. STUDY TYPE: Retrospective. SUBJECTS: A neuropathologist regraded gliomas of 237 patients into WHO 2016 and 2021 from 2007 criteria. FIELD STRENGTH/SEQUENCE: Multicentric 0.5 to 3 Tesla; pre- and post-contrast T1-weighted, T2-weighted, and fluid-attenuated inversion recovery. ASSESSMENT: Radiomic features were selected using random forest-recursive feature elimination. The synthetic minority over-sampling technique (SMOTE) was implemented for data augmentation. Stratified 10-fold cross-validation with and without SMOTE was used to evaluate 11 classifiers for 3-grade (2, 3, and 4; WHO 2016 and 2021) and 2-grade (low and high grade; WHO 2007 and 2021) classification. Additionally, we developed the models on data randomly divided into training and test sets (mixed-data analysis), or data divided based on the centers (independent-data analysis). STATISTICAL TESTS: We assessed ML classifiers using sensitivity, specificity, accuracy, and the area under the receiver operating characteristic curve (AUC). Top performances were compared with a t-test and categorical data with the chi-square test using a significance level of P < 0.05. RESULTS: In the mixed-data analysis, Stacking Classifier without SMOTE achieved the highest accuracy (0.86) and AUC (0.92) in 3-grade WHO 2021 grouping. The results of WHO 2021 were significantly better than WHO 2016 (P-value<0.0001). In the 2-grade analysis, ML achieved 1.00 in all metrics. In the independent-data analysis, ML classifiers showed strong discrimination between grade 2 and 4, despite lower performance metrics than the mixed analysis. DATA CONCLUSION: ML algorithms performed better in glioma tumor grading based on WHO 2021 criteria. Nonetheless, the clinical use of ML classifiers needs further investigation. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Differentiating a pachychoroid and healthy choroid using an unsupervised machine learning approach.

The purpose of this study was to introduce a new machine learning approach for differentiation of a pachychoroid from a healthy choroid based on enhanced depth-optical coherence tomography (EDI-OCT) imaging. This study included EDI-OCT images of 103 eyes from 82 patients with central serous chorioretinopathy or pachychoroid pigment epitheliopathy, and 103 eyes from 103 age- and sex-matched healthy subjects. Choroidal features including choroidal thickness (CT), choroidal area (CA), Haller layer thickness (HT), Sattler-choriocapillaris thickness (SCT), and the choroidal vascular index (CVI) were extracted. The Haller ratio (HR) was obtained by dividing HT by CT. Multivariate TwoStep cluster analysis was performed with a preset number of two clusters based on a combination of different choroidal features. Clinical criteria were developed based on the results of the cluster analysis, and two independent skilled retina specialists graded a separate testing dataset based on the new clinical criteria. TwoStep cluster analysis achieved a sensitivity of 1.000 (95-CI: 0.938-1.000) and a specificity of 0.986 (95-CI: 0.919-1.000) in the differentiation of pachy- and healthy choroid. The best result for identification of pachychoroid was obtained for a combination of CT, HR, and CVI, with a correct classification rate of 0.993 (95-CI: 0.980-1.000). Based on the relative variable importance (RVI), the cluster analysis prioritized the choroidal features as follows: HR (RVI: 1.0), CVI (RVI: 0.87), CT (RVI: 0.70), CA (RVI: 0.59), and SCT (RVI: 0.27). After performing a receiver operating characteristic curve analysis on the cluster membership variable, a cutoff point of 389 µm and 0.79 was determined for CT and HR, respectively. Based on these clinical criteria, a sensitivity of 0.793 (95-CI: 0.611-0.904) and a specificity of 0.786 (95-CI: 0.600-0.900) and 0.821 (95-CI: 0.638-0.924) were achieved for each grader. Cohen's kappa of inter-rater reliability was 0.895. Based on an unsupervised machine learning approach, a combination of the Haller ratio and choroidal thickness is the most valuable factor in the differentiation of pachy- and healthy choroids in a clinical setting.

Effects of Immune System-Related Medications on COVID-19 Outcome in a Cohort of Iranian Patients: Preliminary Report of a Data Mining Study.

BACKGROUND: Regulation of the immune system is critical for fighting against viral infections. Both suppression and hyperactivity of the immune system result in failure of treatment. The present study was designed to show the effects of immune system-related medications on mortality and length of stay (LOS) in a cohort of Iranian patients with coronavirus disease 2019 (COVID-19). METHODS: A data mining study was performed on 6417 cases of COVID-19 covered by 17 educational hospitals of Iran University of Medical Sciences, Tehran. Association of a researcher-designed drug list with death and LOS was studied. For death outcome, logistic regression was used reporting odds ratio (OR) with 95% confidence interval (CI). For LOS, right censored Poisson regression was used reporting incidence rate ratio (IRR) with 95% CI. RESULTS: Among the corticosteroids, prednisolone was a risk factor on death (OR = 1.41, 95%CI = 1.03 - 1.94). This association was increased after adjustment of age interactions (OR = 3.45, 95%CI = 1.01 - 11.81) and was removed after adjustment of ICU admission interactions (OR = 2.64, 95%CI = 0.70 - 9.92). Hydroxychloroquine showed a protecting effect on death (OR = 0.735, 95%CI = 0.627 - 0.862); however, this association was removed after adjustment of age interactions (OR = 0.76, 95%CI = 0.41 - 1.40). Among the antivirals, oseltamivir showed a protecting effect on death (OR = 0.628, 95%CI = 0.451 - 0.873); however, this association was removed after adjustment of age interactions (OR = 0.45, 95%CI = 0.11 - 1.82). For reduction of LOS, the only significant association was for hydroxychloroquine (IRR = 0.85, 95%CI = 0.79 - 0.92). CONCLUSION: The results of such data mining studies can be used in clinics until completing the evidence. Hydroxychloroquine may reduce mortality in some specific groups; however, its association may be confounded by some latent variables and unknown interactions. Administration of corticosteroids should be based on the conditions of each case.

Association of dietary insulinaemic potential and odds of non-alcoholic fatty liver disease among adults: A case-control study.

BACKGROUND: Hyperinsulinaemia is considered as a major risk factor for the development of a myriad of chronic diseases. We examined the association between the dietary insulinaemic potential and the odds of non-alcoholic fatty liver disease (NAFLD) among Iranian adults. METHODS: After being subjected to a liver ultrasound, 166 patients with NAFLD and 200 controls were included in the study. The dietary intakes and the physical activity levels of the participants were evaluated using a validated semi-quantitative food frequency questionnaire and the International Physical Activity Questionnaire (short IPAQ), respectively. The insulinaemic potential of the diet was assessed by computing the scores of the Empirical Dietary Index for Hyperinsulinemia (EDIH) and the Empirical Dietary Index for Insulin Resistance (EDIR). RESULTS: Compared with the control subjects, patients with NAFLD were significantly older; had higher values for body mass index, fasting blood sugar, triglycerides, low-density lipoprotein cholesterol, total cholesterol and alanine transaminase; and were more likely to smoke. Moreover, NAFLD patients had significant lower levels of high-density lipoprotein cholesterol and were less likely to perform physical activity. The risk of NAFLD was higher in the individuals in the highest tertile of the EDIH (odds ratio [OR] = 2.79; 95% confidence interval [CI] = 1.32-5.90; p value for trend < 0.05) and EDIR (OR = 2.42; 95% CI = 1.22-4.79; p value for trend < 0.05) compared to those in the lowest tertile of these scores. CONCLUSIONS: Our study indicates that a higher dietary insulinaemic potential is associated with an increased risk of NAFLD.

The effects of quinoa seed supplementation on cardiovascular risk factors: A systematic review and meta-analysis of controlled clinical trials.

This meta-analysis was designed to determine the effect of quinoa seed on cardiovascular disease (CVD) risk factors in adults. PubMed, Scopus, ISI Web of Science, and Cochrane library were searched electronically from their inception to February 2020 to identify eligible RCTs. We calculated the pooled estimates of weighted mean differences (WMDs) and their 95% confidence intervals (CIs) by using random-effects models. Five eligible RCTs representing 206 subjects were enrolled. The pooled result showed that quinoa seed supplementation significantly lowered the body weight (WMD: -1.26 kg, 95% CI: -2.35, -0.18, p = .02), waist circumference (WC) (WMD: -1.15 cm, 95% CI: -2.08, -0.21, p = .01), fat mass (FM) (WMD: -0.59%, 95% CI: -1.14, -0.03, p = .03), insulin serum level (WMD: -0.86 pmol/L, 95% CI: -13.38, -1.59, p = .01), triglyceride (TG) (WMD: -7.20 mg/dl, 95% CI: -9.52, -4.87, p < .001), total cholesterol (TC) (WMD: -6.86 mg/dl, 95% CI: -10.64, -3.08, p < .001), and low density lipoprotein (LDL) (WMD: -3.08 mg/dl, 95% CI: -5.13, -1.03, p = .003) levels. However, no significant changes were seen in other markers (p > .05). The current evidence suggests that quinoa seed might be utilized as a possible new effective and safe supplementary option to better prevent and control CVD in humans.