Interferons Dominate Damage and Activity in Juvenile Scleroderma.

Juvenile scleroderma is a heterogeneous group of diseases associated with sclerotic skin lesions, grouped as juvenile systemic sclerosis systemic sclerosis) and juvenile localized scleroderma. This study aims to measure the cytokine and chemokine levels involved in interferon signaling in patients with juvenile scleroderma and determine their correlation with disease severity. METHOD: Twenty-nine juvenile localized scleroderma five juvenile systemic sclerosis, and nine healthy controls were included in the study. Patients with juvenile localized scleroderma were scored according to the LoSAI (LoSCAT activity index), LoSDI (LoSCAT damage index), and PGA-A (physician global assessment-activity) indices. Cytokines and chemokines involved in interferon gene signaling (IL-1, IL-6, IL-8, IP-10, MCP1, TNF-α, CXCL-11, IFN-α, IFN-ß, IFN-γ) and interferon-stimulated genes (ISGs) including IFI27, IFI44, ISIG15, IFIT1, OAS1, RSAD2 were measured by ELISA and RT-PCR method respectively. RESULTS: A significant increase in IFN-α, IFN-ß, IFN-γ, TNF-α, IL -1, IL -6 IL -8, IP-10, and MCP1 levels was observed in patients with juvenile systemic sclerosis compared with the healthy control group. Furthermore, IFN- α and IP-10 were elevated in both juvenile localized scleroderma and juvenile systemic sclerosis compared to the healthy control group. IFN-γ and IFN-α positively correlated with LoSAI and LoSDI levels, respectively. According to PGA-A analysis, IFN-ß, IFN-γ, TNF-α, IL -8, IP10, MCP1, and CXCL11 were significantly higher in active disease than in the inactive state in both groups. CONCLUSION: The results suggest that interferon signaling may be impaired in patients with juvenile scleroderma. Significant changes were observed in cytokines and genes related to IFN signaling, which may have a crucial role in monitoring disease activity. In addition, we have gained important insights into the possibility of using IFN-α and IFN-γ as biomarkers for monitoring juvenile scleroderma activity and damage.

Earlier and more aggressive treatment with biologics may prevent relapses and further new organ involvement in Behçet's disease.

OBJECTIVE: Immunosuppressives (IS) are the choice of treatment for major organ involvement in Behçet's disease (BD). In this study, we aimed to investigate the relapse rate and new major organ development in BD under ISs during long-term follow-up. METHODS: The files of 1114 BD patients followed in Marmara University Behçet's Clinic were analyzed retrospectively. Patients with a follow-up less than 6 months were excluded. Conventional IS and biologic treatment courses were compared. 'Events under IS' were defined as a relapse of the same organ and/or new major organ development in patients receiving ISs. RESULTS: Among 806 patients included in the final analysis (male: 56%, age at diagnosis: 29 (23-35) years, median follow-up time: 68 (33-106) months). Major organ involvement was present in 232 (50.5%) patients at diagnosis, and 227 (49.5%) developed new major organ involvement during follow-up. Major organ involvement developed earlier in males (p = 0.012) and in patients with a first-degree relative history of BD (p = 0.066). ISs were given mostly for major organ involvement (86.8%, n = 440). Overall, 36% of the patients had a relapse or new major organ involvement under ISs (relapse: 30.9%, new major organ involvement: 11.6%.) 'Events under IS' (35.5% vs 20.8%, p = 0.004), and relapses (29.3% vs 13.9%, p = 0.001) were more common with conventional ISs compared to biologics. CONCLUSION: Any major event under ISs was less common with biologics compared to conventional ISs in patients with BD. These results suggest that earlier and more aggressive treatment may be an option in BD patients who had the highest risk for severe disease course.

Disrupted epithelial permeability as a predictor of severe COVID-19 development.

BACKGROUND: An impaired epithelial barrier integrity in the gastrointestinal tract is important to the pathogenesis of many inflammatory diseases. Accordingly, we assessed the potential of biomarkers of epithelial barrier dysfunction as predictive of severe COVID-19. METHODS: Levels of bacterial DNA and zonulin family peptides (ZFP) as markers of bacterial translocation and intestinal permeability and a total of 180 immune and inflammatory proteins were analyzed from the sera of 328 COVID-19 patients and 49 healthy controls. RESULTS: Significantly high levels of circulating bacterial DNA were detected in severe COVID-19 cases. In mild COVID-19 cases, serum bacterial DNA levels were significantly lower than in healthy controls suggesting epithelial barrier tightness as a predictor of a mild disease course. COVID-19 patients were characterized by significantly elevated levels of circulating ZFP. We identified 36 proteins as potential early biomarkers of COVID-19, and six of them (AREG, AXIN1, CLEC4C, CXCL10, CXCL11, and TRANCE) correlated strongly with bacterial translocation and can be used to predict and discriminate severe cases from healthy controls and mild cases (area under the curve (AUC): 1 and 0.88, respectively). Proteomic analysis of the serum of 21 patients with moderate disease at admission which progressed to severe disease revealed 10 proteins associated with disease progression and mortality (AUC: 0.88), including CLEC7A, EIF4EBP1, TRANCE, CXCL10, HGF, KRT19, LAMP3, CKAP4, CXADR, and ITGB6. CONCLUSION: Our results demonstrate that biomarkers of intact or defective epithelial barriers are associated with disease severity and can provide early information on the prediction at the time of hospital admission.

The effect of elastic therapeutic taping and rigid taping on pain, functionality, and tissue temperature in lumbar radiculopathy: a randomized controlled study.

PURPOSE: To compare the therapeutic effects of different taping materials and techniques on pain, functionality, and tissue temperature in patients with lumbar radiculopathy. Methods: Patients with lumbar radiculopathy were included in the study (n = 51). Patients were randomly divided into three groups, which were the elastic taping (n = 17), rigid taping (n = 17), and placebo taping groups (n = 17). All patients were enrolled in a physiotherapy and rehabilitation program that included thermotherapy, electrotherapy, and exercise five times a week for 2 weeks. The pain was measured before and after treatment using the Visual Analogue Scale. Functionality and quality of life were measured using the Oswestry Low Back Pain Disability Questionnaire and Roland-Morris Disability Questionnaire. The tissue temperature of the treated area in the lumbar region was measured by digital electronic infra-red thermography. Results: After the treatment, pain, functionality, and quality of life were improved in all groups (p < 0.05). Elastic taping was more effective in decreasing pain and increasing functionality than placebo taping (p < 0.05), but no difference was observed between placebo taping and rigid tapping. Local tissue temperature did not change before and after treatment in the elastic taping group (p > 0.05). Tissue temperature increased in the rigid and placebo taping groups (p < 0.05). Conclusion: Taping therapy in patients with lumbar radiculopathy has a positive effect on pain and functional status. Elastic taping can be recommended for clinical use because its effect is superior in some recovery parameters and its ease of use.

Hemophagocytic Lymphohistiocytosis Related to Tuberculosis Disease.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, albeit potentially fatal, condition in which fever, hepatosplenomegaly, and cytopenia predominate the clinical picture. Although it may be primary, it may also develop secondary to various etiologies. Herein, we aimed to report a patient who was diagnosed with pulmonary tuberculosis, developed fever and cytopenia during follow-up, and received immunomodulatory therapy together with antituberculosis therapy for the diagnosis of HLH. Sequencing of PRF1 showed heterozygous mutation. Although primary HLH has been detected in infants and children, genetic mutation of genes should be considered a differential diagnosis of HLH even in the adolescent. HOW TO CITE THIS ARTICLE: Erdogan S, Çakir D, Bozkurt T, Karakayali B, Kalin S, Koç B, et al. Hemophagocytic Lymphohistiocytosis Related to Tuberculosis Disease. Indian J Crit Care Med 2020;24(1):63-65.

Optimization of the effect of microelectrodes on Ni2+ removal in three-dimensional electrode system.

This study investigated Ni+2 removal performance in 3DER reactors where electrocoagulation mechanisms and microelectrodes are used together. EDTA modification was carried out on the granule-activated carbon surface to increase the efficiency and affinity of microelectrodes against Ni+2 molecules. The grafting was examined using BET, FT-IR, SEM, EDS, and the elemental mapping methods. With the surface analyses made in this study, it was revealed that EDTA modification on granulated activated carbon was successfully performed. Also, 8.48%wt by mass of EDTA grafting on granular activated carbon was possible. EDTA functionalization did not affect the surface pore structures of CAC much. Under 10 V potential, 97.82% Ni removal efficiency was obtained with 2D in 35 min, while 96.69% removal in 10 min and 100% removal in 15 min were obtained in the 3D reactor. The Ni+2 removal mechanism in 3DER reactors has been determined to conform to the pseudo-second-order kinetic model. The k2 value obtained for 10 V (1.36 10-2) is 27 times the k2 value obtained for 5 V for 3DER reactors. In addition, using central composite design (CCD), operational parameters such as time, concentration, and potential difference affecting Ni+2 removal in 3DER reactors have been optimized. The most influential parameter is the applied voltage, followed by time and concentration. It has been determined that 3DER reactors using EDTA-modified microelectrodes are highly efficient and suitable for Ni+2 removal.

Case Report of a Successful Pediatric Central Venovenous Extracorporeal Life Support via Right Atrium-Pulmonary Artery Cannulation for Severe Chest Trauma and Hemorrhagic Shock.

Hypoxemic arrests due to severe traumatic pulmonary injury may not respond to usual medical support. Extracorporeal life support (ECLS) can be life-saving; adequate flows are needed in this setting along with a careful choice of anticoagulation strategies to minimize bleeding. A 44 month old child, who presented with severe blunt chest trauma after being run over by a truck was resuscitated with active compressions and code medications seven times before arrival to the intensive care unit. Failure to adequately oxygenate led to an unconventional approach with cannulations of the right atrium (RA) and pulmonary artery (PA) via sternotomy. Anticoagulation regimen started after bleeding had slowed down with active transfusion of blood products and consisted of low-dose heparin and alprostadil infusions for the initial 48 hours. Heparin was adjusted per institutional guidelines thereafter. Physiologically veno-venous central approach enabled fast stabilization due to full oxygenation without recirculation. Additionally, the dual anticoagulation regimen was safe for circuit maintenance. The described method can be considered in small children with similar risks and conditions.

Re-analysis of whole-exome sequencing data reveals a novel splicing variant in the SLC2A1 in a patient with GLUT1 Deficiency Syndrome 1 accompanied by hemangioma: a case report.

BACKGROUND: GLUT1 Deficiency Syndrome 1 (GLUT1DS1) is a neurological disorder caused by either heterozygous or homozygous mutations in the Solute Carrier Family 2, Member 1 (SLC2A1) gene. SLC2A1 encodes Glucose transporter type 1 (GLUT1) protein, which is the primary glucose transporter at the blood-brain barrier. A ketogenic diet (KD) provides an alternative fuel for brain metabolism to treat impaired glucose transport. By reanalyzing exome data, we identified a de novo heterozygous SLC2A1 variant in a girl with epilepsy. After reversed phenotyping with neurometabolic tests, she was diagnosed with GLUT1DS1 and started on a KD. The patient's symptoms responded to the diet. Here, we report a patient with GLUT1DS1 with a novel SLC2A1 mutation. She also has a hemangioma which has not been reported in association with this syndrome before. CASE PRESENTATION: A 5-year 8-month girl with global developmental delay, spasticity, intellectual disability, dysarthric speech, abnormal eye movements, and hemangioma. The electroencephalography (EEG) result revealed that she had epilepsy. Magnetic resonance imaging (MRI) showed that non-specific white matter abnormalities. Whole Exome Sequencing (WES) was previously performed, but the case remained unsolved. The re-analysis of WES data revealed a heterozygous splicing variant in the SLC2A1 gene. Segregation analysis with parental DNA samples indicated that the variant occurred de novo. Lumbar puncture (LP) confirmed the diagnosis, and the patient started on a KD. Her seizures responded to the KD. She has been seizure-free since shortly after the initiation of the diet. She also had decreased involuntary movements, her speech became more understandable, and her vocabulary increased after the diet. CONCLUSIONS: We identified a novel de novo variant in the SLC2A1 gene in a patient who previously had a negative WES result. The patient has been diagnosed with GLUT1DS1. The syndrome is a treatable condition, but the differential diagnosis is not an easy process due to showing a wide range of phenotypic spectrum and the overlapping symptoms with other neurological diseases. The diagnosis necessitates a genomic testing approach. Our findings also highlight the importance of re-analysis to undiagnosed cases after initial WES to reveal disease-causing variants.