Simultaneous L1-2 Bulged Disc and Mobile Spinal Schwannoma Causing Cauda Equina Syndrome: A Rare Case Report.

BACKGROUND Aside from the rarity of mobile spinal schwannomas, the coexistence of these tumors with herniated intervertebral disc is also scarce. Furthermore, cauda equina syndrome (CES), as a manifestation of intraspinal schwannomas has been reported rarely. Described here is a case of simultaneous lumbar disc bulge and mobile spinal schwannoma presented with intermittent symptoms of CES. CASE REPORT A 62-year-old man presented with severe but intermittent leg pain for 2 weeks, which later progressed to an episode of lower extremity weakness and difficulty in urination. Magnetic resonance imaging revealed an intraspinal tumor that moved in position relative to the L1-2 disc bulge on scans 6 h apart, with associated spontaneous regression in symptoms. The tumor was found to be a mobile spinal schwannoma, originated from a nerve root. A standard microdissection technique was used to remove the tumor through a spinous process-sparing unilateral approach, with complete laminectomy of L1. Use of intraoperative ultrasound facilitated the accurate tumor localization. Postoperatively, the patient no longer had symptoms. CONCLUSIONS This report presents a combination of a common spinal pathology, intervertebral disc herniation, alongside a rare condition, mobile spinal schwannoma, whose uncommon clinical manifestations, such as CES can cause irreversible neurological deficits. Surgeons need to remain vigilant of potential atypical scenarios when treating patients. Surgical treatment challenges regarding the mobility of tumors, such as accurate localization, should be addressed using intraoperative imaging to avoid wrong-level surgery. To mitigate the irreversible neurological complications, patients should receive comprehensive information for alarming signs of CES.

Targeting the NF-κB pathway as a potential regulator of immune checkpoints in cancer immunotherapy.

Advances in cancer immunotherapy over the last decade have led to the development of several agents that affect immune checkpoints. Inhibitory receptors expressed on T cells that negatively regulate the immune response include cytotoxic T­lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD1), which have been studied more than similar receptors. Inhibition of these proteins and other immune checkpoints can stimulate the immune system to attack cancer cells, and prevent the tumor from escaping the immune response. However, the administration of anti-PD1 and anti-CTLA4 antibodies has been associated with adverse inflammatory responses similar to autoimmune diseases. The current review discussed the role of the NF-κB pathway as a tumor promoter, and how it can govern inflammatory responses and affect various immune checkpoints. More precise knowledge about the communication between immune checkpoints and NF-κB pathways could increase the effectiveness of immunotherapy and reduce the adverse effects of checkpoint inhibitor therapy.

Role of non-coding RNAs as new therapeutic targets in regulating the EMT and apoptosis in metastatic gastric and colorectal cancers.

Colorectal cancer (CRC) and gastric cancer (GC), are the two most common cancers of the gastrointestinal tract, and are serious health concerns worldwide. The discovery of more effective biomarkers for early diagnosis, and improved patient prognosis is important. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), can regulate cellular processes such as apoptosis and the epithelial-mesenchymal transition (EMT) leading to progression and resistance of GC and CRC tumors. Moreover these pathways (apoptosis and EMT) may serve as therapeutic targets, to prevent metastasis, and to overcome drug resistance. A subgroup of ncRNAs is common to both GC and CRC tumors, suggesting that they might be used as biomarkers or therapeutic targets. In this review, we highlight some ncRNAs that can regulate EMT and apoptosis as two opposite mechanisms in cancer progression and metastasis in GC and CRC. A better understanding of the biological role of ncRNAs could open up new avenues for the development of personalized treatment plans for GC and CRC patients.

Diagnostic Accuracy of Ultrasonography for Identification of Elbow Fractures in Children; a Systematic Review and Meta-analysis.

Introduction: In spite of the results of previous studies regarding the benefits of ultrasonography for diagnosis of elbow fractures in children, the exact accuracy of this imaging modality is still under debate. Therefore, in this diagnostic systematic review and meta-analysis, we aimed to investigate the accuracy of ultrasonography in this regard. Methods: Two independent reviewers performed systematic search in Web of Science, Embase, PubMed, Cochrane, and Scopus for studies published from inception of these databases to May 2023. Quality assessment of the included studies was performed using Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2). Meta-Disc software version 1.4 and Stata statistical software package version 17.0 were used for statistical analysis. Results: A total of 648 studies with 1000 patients were included in the meta-analysis. The pooled sensitivity and specificity were 0.95 (95% CI: 0.93-0.97) and 0.87 (95% CI: 0.84-0.90), respectively. Pooled positive likelihood ratio (PLR) was 6.71 (95% CI: 3.86-11.67), negative likelihood ratio (NLR) was 0.09 (95% CI: 0.03-0.22), and pooled diagnostic odds ratio (DOR) of ultrasonography in detection of elbow fracture in children was 89.85 (95% CI: 31.56-255.8). The area under the summary receiver operating characteristic (ROC) curve for accuracy of ultrasonography in this regard was 0.93. Egger's and Begg's analyses showed that there is no significant publication bias (P=0.11 and P=0.29, respectively). Conclusion: Our meta-analysis revealed that ultrasonography is a relatively promising diagnostic imaging modality for identification of elbow fractures in children. However, clinicians employing ultrasonography for diagnosis of elbow fractures should be aware that studies included in this meta-analysis had limitations regarding methodological quality and are subject to risk of bias. Future high-quality studies with standardization of ultrasonography examination protocol are required to thoroughly validate ultrasonography for elbow fractures.

Point-Of-Care Ultrasonography for Identification of Skin and Soft Tissue Abscess in Adult and Pediatric Patients; a Systematic Review and Meta-Analysis.

Introduction: Differentiating the soft tissue abscess from other types of skin and soft tissue infections (SSTIs) poses a particular challenge because they have similar physical evaluation findings, but each disease has a different course, outcome, and treatment. This meta-analysis aimed to investigate the diagnostic accuracy of point-of-care ultrasonography for diagnosis of soft tissue abscess in the emergency departments. Methods: A comprehensive literature search of MEDLINE, Scopus, Web of Science, Embase, and Google Scholar, from inception to January 2023, was conducted to identify relevant studies investigating the diagnostic performance of point-of-care ultrasonography for identification of abscess. Methodological quality of the included studies was assessed using a revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2). Results: The pooled estimates of diagnostic parameters of ultrasonography for diagnosis of abscess were as follows: sensitivity, 0.93 (95% CI: 0.92-0.94); specificity, 0.87 (95% CI: 0.85-0.89), and the area under the summary receiver-operating characteristic (SROC), 0.95. The pooled sensitivity, specificity, and area under the SROC of studies in adult patients were 0.98 (95% CI: 0.92-1), 0.92 (95% CI: 0.86-0.95), and 0.99, respectively. The pooled sensitivity, specificity, and area under the SROC of studies in pediatric patients were 0.9 (95% CI: 0.87-0.92), 0.78 (95% CI: 0.73-0.82), and 0.91, respectively. Conclusion: Our meta-analysis demonstrated that the point-of-care ultrasonography has excellent diagnostic value for the abscess in the emergency department. Furthermore, we found that the diagnostic performance of point-of-care ultrasonography for diagnosis of abscess was higher for adult cases than for pediatric patients.

Diagnostic Accuracy of Ottawa Knee Rule for Diagnosis of Fracture in Patients with Knee Trauma; a Systematic Review and Meta-analysis.

Introduction: In order to improve the efficacy of requesting knee radiography and reduce unnecessary radiation exposure, some clinical decision rules have been proposed for the assessment of knee injuries. Among them, the Ottawa Knee Rule (OKR) was considered as one of the best guidelines with several validation studies. Therefore, in this meta-analysis, we aimed to investigate the accuracy of OKR for diagnosis of fracture in patients presenting with knee trauma. Methods: A systematic search was conducted in PubMed, Web of Science, Scopus, Google Scholar, and EBSCO from inception to September 2022. Quality assessment of the included studies was performed using QUADAS-2 tool. Diagnostic accuracy parameters were analyzed using random-effects model. Statistical analysis was performed using Meta-Disc and Stata softwares. Results: The meta-analysis of the 18 included studies (6702 patients) showed that the pooled sensitivity and specificity of OKR for diagnosis of fractures were 0.98 (95% CI: 0.96-0.99) and 0.43 (95% CI: 0.42-0.45), respectively. The pooled positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 1.56 (95% CI: 1.39-1.75) and 0.12 (95% CI: 0.05-0.26), respectively. The area under curve (AUC) of the hierarchical summary receiver operating characteristic (HSROC) curve was 0.54. Conclusion: This meta-analysis indicates that OKR has a high diagnostic performance for diagnosis of fracture, with a pooled sensitivity of 98% and a pooled specificity of 43%. These results propose potential effects of OKR on reduction of unnecessary radiography, time spent in emergency departments, and direct and indirect costs, which should be confirmed using high-quality studies in the future.

Receptor tyrosine kinase inhibitors in cancer.

Targeted therapy is a new cancer treatment approach, involving drugs that particularly target specific proteins in cancer cells, such as receptor tyrosine kinases (RTKs) which are involved in promoting growth and proliferation, Therefore inhibiting these proteins could impede cancer progression. An understanding of RTKs and the relevant signaling cascades, has enabled the development of many targeted drug therapies employing RTK inhibitors (RTKIs) some of which have entered clinical application. Here we discuss RTK structures, activation mechanisms and functions. Moreover, we cover the potential effects of combination drug therapy (including chemotherapy or immunotherapy agents with one RTKI or multiple RTKIs) especially for drug resistant cancers.

Emerging role of mesenchymal stem/stromal cells (MSCs) and MSCs-derived exosomes in bone- and joint-associated musculoskeletal disorders: a new frontier.

Exosomes are membranous vesicles with a 30 to 150 nm diameter secreted by mesenchymal stem/stromal cells (MSCs) and other cells, such as immune cells and cancer cells. Exosomes convey proteins, bioactive lipids, and genetic components to recipient cells, such as microRNAs (miRNAs). Consequently, they have been implicated in regulating intercellular communication mediators under physiological and pathological circumstances. Exosomes therapy as a cell-free approach bypasses many concerns regarding the therapeutic application of stem/stromal cells, including undesirable proliferation, heterogeneity, and immunogenic effects. Indeed, exosomes have become a promising strategy to treat human diseases, particularly bone- and joint-associated musculoskeletal disorders, because of their characteristics, such as potentiated stability in circulation, biocompatibility, low immunogenicity, and toxicity. In this light, a diversity of studies have indicated that inhibiting inflammation, inducing angiogenesis, provoking osteoblast and chondrocyte proliferation and migration, and negative regulation of matrix-degrading enzymes result in bone and cartilage recovery upon administration of MSCs-derived exosomes. Notwithstanding, insufficient quantity of isolated exosomes, lack of reliable potency test, and exosomes heterogeneity hurdle their application in clinics. Herein, we will deliver an outline respecting the advantages of MSCs-derived exosomes-based therapy in common bone- and joint-associated musculoskeletal disorders. Moreover, we will have a glimpse the underlying mechanism behind the MSCs-elicited therapeutic merits in these conditions.

Cancer stem cells in colorectal cancer: Signaling pathways involved in stemness and therapy resistance.

Colorectal cancer (CRC) is the third cause of cancer death worldwide. Although, in some cases, treatment can increase patient survival and reduce cancer recurrence, in many cases, tumors can develop resistance to therapy leading to recurrence. One of the main reasons for recurrence and therapy resistance is the presence of cancer stem cells (CSCs). CSCs possess a self-renewal ability, and their stemness properties lead to the avoidance of apoptosis, and allow a new clone of cancer cells to emerge. Numerous investigations inidicated the involvment of cellular signaling pathways in embryonic development, and growth, repair, and maintenance of tissue homeostasis, also participate in the generation and maintenance of stemness in colorectal CSCs. This review discusses the role of Wnt, NF-κB, PI3K/AKT/mTOR, Sonic hedgehog, and Notch signaling pathways in colorectal CSCs, and the possible modulating drugs that could be used in treatment for resistant CRC.

Role of m6A modification in dysregulation of Wnt/ß-catenin pathway in cancer.

N6-methyladenosine (m6A) modification is the most abundant post-transcriptional regulation of RNAs in eukaryotes. Dysregulation of m6A readers, writers, and erasers can significantly promote tumorigenesis by altering the expression of various genes. Wnt/ß-catenin is an evolutionarily conserved signaling pathway that has recently been linked to the pathogenesis of many cancers. Given the significance of this pathway in regulating normal tissue homeostasis and stem cell differentiation, a subtle understanding of the molecular mechanism underlying its dysregulation is required for effective targeting. There is mounting evidence that m6A regulators are highly implicated in the dysregulation of the Wnt/ß-catenin signaling pathway. Since m6A regulators can affect Wnt pathway components and dysregulation of either leads to carcinogenesis, this study aims to clarify the relationship between m6A regulators and the Wnt/ß-catenin signaling pathway to investigate their combined impact on tumorigenesis.

The emerging role of regulatory cell-based therapy in autoimmune disease.

Autoimmune disease, caused by unwanted immune responses to self-antigens, affects millions of people each year and poses a great social and economic burden to individuals and communities. In the course of autoimmune disorders, including rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, and multiple sclerosis, disturbances in the balance between the immune response against harmful agents and tolerance towards self-antigens lead to an immune response against self-tissues. In recent years, various regulatory immune cells have been identified. Disruptions in the quality, quantity, and function of these cells have been implicated in autoimmune disease development. Therefore, targeting or engineering these cells is a promising therapeutic for different autoimmune diseases. Regulatory T cells, regulatory B cells, regulatory dendritic cells, myeloid suppressor cells, and some subsets of innate lymphoid cells are arising as important players among this class of cells. Here, we review the roles of each suppressive cell type in the immune system during homeostasis and in the development of autoimmunity. Moreover, we discuss the current and future therapeutic potential of each one of these cell types for autoimmune diseases.