The uveitis and its relationship with disease activity and quality of life in Moroccan children with juvenile idiopathic arthritis

The aim of our study is to investigate ocular involvement in juvenile idiopathic arthritis (JIA) and its relationship with disease activity and quality of life in Moroccan patients who suffer from JIA. This is a cross-sectional study conducted between January and June 2012 which includes patients with juvenile idiopathic arthritis (n?=?30). All patients have undergone clinical and paraclinical assessment of JIA and a complete eye examination. Functional impairment is assessed by the Childhood Health Assessment Questionnaire while visual function is studied by the Effect of Youngsters’ Eyesight in Quality of Life instrument (EYE-Q). Quality of life is assessed using the Pediatric Quality of Life Inventory Version 4.0 (PedsQL 4.0). Four patients (13.33 %) have uveitis with a confidence interval between 3.4 and 30.7. Involvement is bilateral in three children (75 %). One patient (25 %) has elevated intraocular pressure with loss of the right eye due to glaucoma. There is a strong but not significant relationship between uveitis and the number of awakenings (r?=?0.71, p?=?0.69) and morning stiffness (r?=?3.05, p?=?0, 21). This relationship is moderate with erythrocyte sedimentation rate (r?=?0.48, p?=?0.78) and C-reactive protein (r?=?0.25, p?=?0.88). A strong but not significant association is found between the overall quality of life assessed by the PedsQL 4.0 and visual function assessed by EYE-Q in the uveitis group (r?=??0.64, p?=?0.55). This study suggests that uveitis associated with JIA can present serious complications and could have a direct relationship with the activity of the JIA as well as with the quality of life of the patient.     

Mortality and long-term functional outcome associated with intracranial pressure after traumatic brain injury

Purpose

Elevated intracranial pressure (ICP) has been associated with increased mortality in patients with severe traumatic brain injury (TBI). We have examined whether raised ICP is independently associated with mortality, functional status and neuropsychological functioning in adult TBI patients.

Methods

Data from a randomized trial of 499 participants were secondarily analyzed. The primary endpoints were mortality and a composite measure of functional status and neuropsychological function (memory, speed of information processing, executive function) over a 6-month period. The area under the curve of the ICP profile (average ICP) during the first 48?h of monitoring was the main predictor of interest. Multivariable regression was used to adjust for a priori defined confounders: age, Glasgow Coma Score, Abbreviated Injury Scale–head and hypoxia.

Results

Of the participants, 365 patients had complete 48-h ICP data. The overall 6-month mortality was 18?%. The adjusted odds ratio of mortality comparing 10-mmHg increases in average ICP was 3.12 (95?% confidence interval 1.79, 5.44; p?<?0.01). Overall, higher average ICP was associated with decreased functional status and neuropsychological functioning (p?<?0.01). Importantly, among survivors, increasing average ICP was not independently associated with worse performance on neuropsychological testing (p?=?0.46).

Conclusions

Average ICP in the first 48?h of monitoring was an independent predictor of mortality and of a composite endpoint of functional and neuropsychological outcome at the 6-month follow-up in moderate or severe TBI patients. However, there was no association between average ICP and neuropsychological functioning among survivors.     

Bicondylar tibial fractures: Internal or external fixation?

Bicondylar fractures of the tibia, representing the Schatzker V and VI fractures represent a challenging problem. Any treatment protocol should aim at restoring articular congruity and the metaphyseo-diaphsyeal dissociation (MDD)—both of these are equally important to long-term outcome. Both internal and external fixations have their proponents, and each method of treatment is associated with its unique features and complications. We review the initial and definitive management of these injuries, and the advantages and disadvantages of each method of definitive fixation. We suggest the use of a protocol for definitive management, using either internal or external fixation as deemed appropriate. This protocol is based on the fracture configuration, local soft tissue status and patient condition. In a nutshell, if the fracture pattern and soft tissue status are amenable plate fixation (single or double) is performed, otherwise limited open reduction and articular surface reconstruction with screws and circular frame is performed.     

Receptor tyrosine kinase signaling in cancer radiotherapy and its targeting for tumor radiosensitization

Purpose: One of the most important implications of ‘Radiation Biology’ research is to improve cancer radiotherapy with minimum side effects. In this regard, combination of chemotherapy with radiation has significantly improved tumor control as well as overall survival in a variety of cancers. However, this has been achieved at the cost of significant normal tissue toxicity, due to the lack of specificity of chemotherapy. Membrane-localized receptor tyrosine kinases (RTKs) have been found to play a driving role in various hallmarks of cancer. Moreover, an early successful clinical trial using RTK-antagonist (cetuximab) to improve tumor radiosensitivity has led to an advancement in this field of research. However, a comprehensive review integrating these findings of various oncogenic RTKs, from basic radiobiology-to-radiotherapy clinical trials, is lacking in literature. Therefore, the present review analyses relevant in-vitro, in-vivo, preclinical/clinical studies and postulates the concept of ‘Radiation Biology of RTKs in Cancer’.

Conclusions: The present review elucidates the effect of IR on various oncogenic RTKs and their mechanisms, downstream signaling, intracellular translocations, their role in the repair of radiation-induced DNA damage and post-irradiation survival. Based on the knowledge derived from RTK biology and the analysis of relevant clinical trials, this review attempts to identify radiobiological considerations, which could be implemented in future trials, combining radiotherapy with RTK-antagonist. Additionally, we identify the radiosensitizing potential of recently developed RTK-targeted nanoformulations. This review would probably change the Radiation Oncologist’s view for translation of tumor-specific radiosensitization in clinic.     

Abnormal expression of MHC class II and ICAM-1 by melanocytes in vitiligo

The relationship between damage to cutaneous melanocytes and antimelanocyte autoimmunity in vitiligo is unclear. We have demonstrated abnormal expression of MHC class II molecules by perilesional melanocytes in 13/21 patients with vitiligo and a six-fold increase in the number expressing the intercellular adhesion molecule ICAM-1. These molecules have important roles in normal antigen presentation and activation of helper T lymphocytes, and their expression by melanocytes may contribute to the abnormal immune response in vitiligo. MHC class II is not expressed by melanocytes in psoriasis and is unlikely to be induced in vitiligo by cytokines released from activated non-melanocyte-specific T lymphocytes.     

Targeting the CSF1/CSF1R axis is a potential treatment strategy for malignant meningiomas

BackgroundMalignant meningiomas are fatal and lack effective therapy. As M2 macrophages are the most prevalent immune cell type in human meningiomas, we hypothesized that normalizing this immunosuppressive population would be an effective treatment strategy.MethodsWe used CIBERSORTx to examine the proportions of 22 immune subsets in human meningiomas. We targeted the colony-stimulating factor 1 (CSF1) or CSF1 receptor (CSF1R) axis, an important regulator of macrophage phenotype, using monoclonal antibodies (mAbs) in a novel immunocompetent murine model (MGS1) for malignant meningioma. RNA sequencing (RNA-seq) was performed to identify changes in gene expression in the tumor microenvironment (TME). Mass cytometry was used to delineate changes in immune subsets after treatment. We measured patients’ plasma CSF1 levels using ELISA and CSF1R expression using multiplex quantitative immunofluorescence in a human meningioma tissue microarray.ResultsHuman meningiomas are heavily enriched for immunosuppressive myeloid cells. MGS1 recapitulates the TME of human meningiomas, including an abundance of myeloid cells, a paucity of infiltrating T cells, and low programmed death ligand 1 (PD-L1) expression. Treatment of murine meningiomas with anti-CSF1/CSF1R, but not programmed cell death receptor 1 (PD-1), mAbs abrogate tumor growth. RNA-seq and mass cytometry analyses reveal a myeloid cell reprogramming with limited effect on T cells in the TME. CSF1 plasma levels are significantly elevated in human patients, and CSF1R is highly expressed on CD163⁺ macrophages within the human TME.ConclusionOur findings suggest that anti-CSF1/CSF1R antibody treatment may be an effective normalization cancer immunotherapy for malignant meningiomas.