Treatment with biological agents has become standard of care in treatment of immune-mediated diseases (IMD), including rheumatoid arthritis and psoriatic arthritis. Yet, a significant proportion of patients experience loss of response to biologics, need treatment escalation, or develop side effects. During the past decade, new biologic agents with different targeted molecular pathways have been approved for treatment of IMD, introducing the possibility of concomitant dual biologic therapy. The role of dual biologic therapy targeting different inflammatory pathways has become an area of great interest in the field of IMD, addressing the unmet clinical need of patients with refractory diseases and treatment of comorbidities, such as osteoporosis, asthma, atopic dermatitis, and urticaria. Despite the increasing use of biologics as a dual therapy across different indications, there is a paucity of data concerning the safety of the simultaneous use of more than one biological agents. The purpose of this review is to summarize the current literature on the use of dual biologics in patients with rheumatoid arthritis and psoriatic arthritis, addressing the potential adverse effects associated with combination therapy, and highlighting future directions in the use of this novel therapeutic modality.
Idiopathic inflammatory myopathies (IIM) are a rare group of disorders that feature progressive immune-mediated skeletal muscle destruction along with skin, lung, and joint involvement. Management of IIMs necessitates glucocorticoid therapy followed by conventional steroid-sparing agents to control disease activity. In the settings of refractory myositis or life-threatening manifestations, e.g. lung involvement or oropharyngeal dysphagia, second-line therapies are needed to minimize disease burden, avoid end-organ damage and steroid toxicity, and decrease mortality. These therapies may include biological disease-modifying antirheumatic drugs (bDMARDs), and to a lesser extent, targeted synthetic disease-modifying antirheumatic drugs (TSD). This article reviews the current use of bDMARDs, e.g. intravenous immunoglobulin and rituximab, and a TSD—Janus kinase inhibitors (JAKI)—along with their indications, efficacy, and safety in managing IIM.
Giant cell arteritis (GCA) is the most prevalent subtype of vasculitis in adults. In recent years, there has been substantial improvement in the diagnosis and treatment of GCA, mainly attributed to the introduction of highly sensitive diagnostic tools, incorporation of modern imaging modalities for diagnosis and monitoring of large-vessel vasculitis, and introduction of highly effective novel biological therapies that have revolutionized the field of GCA. This article reviews state-of-the-art approaches for the diagnosis, monitoring, and treatment options of GCA.
Systemic sclerosis (SSc) is a chronic immune-mediated disease characterized by microangiopathy, immune dysregulation, and progressive fibrosis of the skin and internal organs. Though not fully understood, the pathogenesis of SSc is dominated by microvascular injury, endothelial dysregulation, and immune response that are thought to be associated with fibroblast activation and related fibrogenesis. Among the main clinical subsets, diffuse SSc (dSSc) is a progressive form with rapid and disseminated skin thickening accompanied by internal organ fibrosis and dysfunction. Despite recent advances and multiple randomized clinical trials in early dSSc patients, an effective disease-modifying treatment for progressive skin fibrosis is still missing, and there is a crucial need to identify new targets for therapeutic intervention. Eotaxin-2 (CCL24) is a chemokine secreted by immune cells and epithelial cells, which promotes trafficking of immune cells and activation of pro-fibrotic cells through CCR3 receptor binding. Higher levels of CCL24 and CCR3 were found in the skin and sera of patients with SSc compared with healthy controls; elevated levels of CCL24 and CCR3 were associated with fibrosis and predictive of greater lung function deterioration. Growing evidence supports the potency of a CCL24-blocking antibody as an anti-inflammatory and anti-fibrotic modulating agent in multiple preclinical models that involve liver, skin, and lung inflammation and fibrosis. This review highlights the role of CCL24 in orchestrating immune, vascular, and fibrotic pathways, and the potential of CCL24 inhibition as a novel treatment for SSc.
Objectives: This review aimed to critically appraise the evidence for biomarkers in blood serum, gingival crevicular fluid (GCF), saliva, and urine in comparison with standard radiographic indices for skeletal maturation assessment.
Materials and Methods: A thorough literature search in multiple databases was conducted for biomarkers in body fluids for skeletal maturation assessed with cervical vertebrae in lateral cephalograms or on hand-wrist radiographs. Different combinations including free text, MeSH terms, and Boolean operators were used. Two researchers used strict inclusion and exclusion criteria to screen title, abstract, and full text, and used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 instrument for risk of bias assessment of individual studies. Meta-analysis was performed on eligible studies using RevMan 5 software.
Results: A total of 344 articles were screened, of which 33 met the inclusion criteria and quality assessment. The skeletal maturity indicators included insulin-like growth factors (IGF-1), alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), dehydroepiandrosterone sulfate (DHEAS), vitamin D binding protein (DBP), parathormone-related protein (PTHrP), osteocalcin, metalloproteins, and serotransferrin (TF) along with different metabolites. At puberty, a significant rise was seen in IGF-1, DBP, ALP, osteocalcin, TF, and BALP. However, the serum DHEAS and PTHrP increased from pre-pubertal to post-pubertal stages. Due to the data heterogeneity, a meta-analysis could be performed on seven studies in total on IGF-1 in serum and blood. Of these, five were included for data in males and six in females, and four studies on IGF-1 in serum and blood. A significant difference in IGF-1 levels was seen between stages of peak pubertal growth spurt (CS3 and CS4) and decelerating pubertal growth (CS5) compared with growth initiation stage (CS2).
Conclusions: Pubertal growth spurts were correlated with peak serum IGF-1 and BALP in both sexes individually. Peak ALP levels in GCF were correlated with the pubertal spurt in a combined sample of males and females. Standard biofluid collection protocols and homogeneity in sampling and methodology are strongly recommended for future research.
Major improvements in medical diagnostics and treatments in Dutch hospital care during the second half of the 19th century led to a shift from a nearly exclusive focus on indigent patients to an increasing proportion of hospital beds dedicated to paying middle-class patients. To accommodate this change, three private non-sectarian hospitals for middle-class patients were established in Amsterdam between 1857 and 1902. However, the two Jewish hospitals in the Dutch capital, the Dutch Jewish Ashkenazi hospital (NIZ), and the Portuguese Jewish hospital (PIZ), initially established exclusively for poor Jews, were much slower to respond to the trend of increasing hospital care for the middle class. This study examines how these hospitals addressed the needs of both poor and middle-class patients in the first decades of the 20th century as well as the success of the Centrale Israelitische Ziekenverpleging (CIZ, Central Jewish hospital) that was established solely for middle-class Jewish patients. The report also investigates how, after the devastation of the Amsterdam Jewish community during WW2, the CIZ managed to remain and today is the only ritually observant Jewish hospital unit in the Netherlands.
Introduction: When authorship disputes arise in academic publishing, research institutions may be asked to investigate the circumstances. We evaluated the association between the prevalence of misattributed authorship and trust in the institution involved.
Methods: We measured trust using a newly validated Opinion on the Institution’s Research and Publication Values (OIRPV) scale (range 1–4). Mayer and Davies’ Organizational Trust for Management Instrument served as control. Association between publication misconduct, gender, institution type, policies, and OIRPV-derived Trust Scores were evaluated.
Results: A total of 197 responses were analyzed. Increased reporting of authorship misconduct, such as gift authorship, author displacement within the authors’ order on the byline, and ghost authorship, were associated with low Trust Scores (P<0.001). Respondents from institutions whose administration had made known (declared or published) their policy on authorship in academic publications awarded the highest Trust Scores (median 3.06, interquartile range 2.25 to 3.56). Only 17.8% favored their administration as the best authority to investigate authorship dispute honestly. Of those who did not list the administration as their preferred option for resolving disputes, 58.6% (95/162) provided a Trust Score <2.5, which conveys mistrust in the institution.
Conclusions: Increased reporting of publication misconducts such as gift authorship, author displacement within the order of the authors’ byline, and ghost authorship was associated with lower Trust Scores in the research institutions. Institutions that made their policies known were awarded the highest Trust Scores. Our results question whether the research institutions’ administrations are the appropriate authority for clarifying author disputes in all cases.
Background: Human papillomavirus HPV is considered to be responsible for 95% of virus-related cancers in many organs. Oropharyngeal carcinoma (OC) is distinguished by the transformation of the healthy epithelium into precancerous cells.
Aim: The current study sought to examine the uneven gene expression of 20 genes among those scanned by microarray for oropharyngeal cancer patients.
Materials and Methods: GSE56142 dataset was extracted from the GEO in NCBI. 24 specimens were evaluated. Gene Ontology (GO), KEGG, and the protein-protein interaction (PPI) were used to depict the biological roles of the genes under investigation using types of software.
Results: Six genes out of 20 in invasive patients had a binding correlation with high expression (PDGFRS, COL6A3, COL1A1, COL3A1, COL2A1, and COL4A1), and only two genes with low expression (CRCT1 and KRT78). The expression levels of 20 genes were examined between patients with OC and head and neck squamous cell carcinoma (HNSCC). The correlation coefficient between highly expressed genes was statistically significant at the p < 0.05 level.
Conclusions: It is crucial to evaluate the high expression of particular genes as diagnostic tumor markers, particularly in the early stages.
Meir Dvorjetski was a Holocaust survivor, teacher, and historian. He is best remembered for his descriptions of the medicine practiced by the Nazis during World War II, as well as the diseases, disorders, syndromes, and deaths resulting from such practice—particularly, though not solely, on the Jewish race. Dvorjetski’s contributions to Holocaust research at Bar-Ilan University in Israel, his underground partisan work, his contributions to society, and his testimony at the Eichmann trial have all been well documented. However, his earlier years—including his survival of the Holocaust, and his less-known medical achievements and contributions to historical records regarding the Holocaust—have not been covered as thoroughly. These latter items are the focus of this paper, with a closing commentary on the relevance of his work for the 21st century.
Movement disorders associated with donepezil have been only rarely reported. Herein, we describe an older woman who developed myoclonus secondary to donepezil. A 61-year-old female presented with brief involuntary twitching. The patient reported that she consulted a general practitioner about 1 month before due to memory complaints. A diagnosis of mild cognitive impairment was made. Donepezil was started. After 4 weeks, she presented to our emergency department due to significant twitching. Multifocal myoclonus was observed. These movements occurred during rest and voluntary movement. Laboratory exams and cerebrospinal fluid analysis were normal. A cranial computed tomography and brain magnetic resonance imaging were unremarkable. Electroencephalography did not show epileptic activity. Electromyography revealed burst durations varying between 50 and 100 ms. Diazepam intravenous was started, which improved her abnormal movement within 1 hour. On the next day, she developed the same clinical symptoms of presentation. Donepezil was discontinued, and clonazepam was started. The patient had a complete recovery from her myoclonus. To the authors’ knowledge, there are six reports of myoclonus secondary to donepezil/galantamine. There is no report of rivastigmine-induced myoclonus. The most frequent presentation was multifocal myoclonus. The management was the discontinuation of the acetylcholinesterase inhibitor. All the individuals recovered within 3 weeks.
