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.

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.

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.

Why mistreatment of medical students is not reported in clinical settings: perspectives of trainees.

Mistreatment of medical students is a major source of stress for them. Studies indicate a high incidence of such mistreatment, especially in clinical settings. In most cases, students who have been mistreated do not report it to the authorities. This study investigated factors related to the failure to report mistreatment. This was a cross-sectional study carried out in Kerman Medical School, Iran. All students in the internship and clerkship stages, as well as residents, were selected through the census method. Experiences of mistreatment and the reasons for not reporting them were evaluated using a questionnaire. The data were analysed with SPSS 19. Ninety-three per cent of the participants experienced mistreatment, but less than half of them reported it. Residents and interns reported emotional and academic mistreatment, respectively, more than other groups. The most common reason for not reporting mistreatment was that the students did not think reporting would accomplish anything. Our study showed that the experience of mistreatment in the clinical setting is common, but the cases reported to the authorities are far fewer than the actual number of cases. Educational systems should make extensive efforts to detect and prevent mistreatment to improve the teaching-learning environment.