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.
The appointment of a new chancellor in 1933 marked the beginning of the Third Reich in Germany. The ideology of the Nazi Party focused on establishing a pure Aryan state characterized by nationalism and racial superiority. Their goals would be achieved through a totalitarian form of government that enforced the subjugation, exclusion, and elimination of those they defined as inferior minorities, particularly Jews, who were depicted as non-human. Implementation of the Nazi ideology required the exclusion of Jewish people and other dissenters, particularly Jewish physicians, from their professions. The exclusion of Jewish physicians, referred to herein as a “Medical Professional Elimination Program,” was gradually imposed on other Jewish professions in nations absorbed by the Third Reich, and particularly enforced by incorporated Austria. Why did German and Austrian doctors support the Nazi racial ideology, the removal of Jewish physicians from every possible sphere of influence, and subsequently participate in criminal medical research and experimentation, as well as euthanasia of perceived non-contributors to society, and become involved in refining the effectiveness of the death camps? Was the Medical Professional Elimination Program an opportunistic political concept, or was it part of an entrenched ideology? With these questions in mind, the lives of four key Nazi physicians and two institutions are examined.
Introduction: Antisemitism and antisemitic incidents have been increasing in United States medical institutions since the Hamas attack of October 7, 2023. Such incidents include anecdotal reports of antisemitic displays at medical school commencements. This study examined unprofessional behavior observed at the commencement ceremonies of the 25 US medical schools top-ranked for research excellence. This issue is significant since these graduates are expected to become future leaders in the field of medicine.
Materials and Methods: Based on publicly available videotaped commencements, we assessed the number of students in the graduating classes wearing non-school-provided regalia, carrying signs, wearing protest buttons, or engaging in verbal protests related to the Israel–terror groups conflict that were either openly antisemitic or potentially offensive or insensitive.
Results: Symbols representing antisemitic themes (keffiyehs and three-part graduation stoles conveying antisemitic messages) were worn by students at just under half (12) of the medical schools. The mean number of students in each school wearing keffiyehs or non-official school stoles was 4.0 (95% confidence interval [CI] 2.2–5.8), ranging from 0%–13% of the classes, or 2.5% of the overall graduating cohort. The wearing of buttons, carrying of banners or signs, verbal protests interrupting the ceremony, or students deviating from script ranged from 0% to 22.5% of graduating students, with a mean of 2.7 per school (95% CI -0.8–6.2), or 1.7% of the medical schools graduating cohort.
Conclusions: We identified unprofessional behavior at commencements of top-ranked medical schools consisting of antisemitism and displaying offensive and insensitive symbols and messaging. There is an urgent need for medical schools in the US to educate medical trainees about the dangers of antisemitism and all forms of hate and insensitivity.
Throughout history, Jewish people have long been recognized for their achievements in the world of medical science. For example, prior to the Holocaust, many outstanding physicians in Germany were Jewish. However, even in the 1930s, refugee European Jewish doctors faced significant barriers when they tried to escape and practice elsewhere because of long-standing prejudices and anti-Jewish quotas in medical schools and hospitals around the world. Eventually quotas fell, and the period after World War II once again saw a tremendous growth in numbers of Jews excelling in medicine internationally. Since the Hamas attack on Israel on October 7, 2023, there has been a resurgence of antisemitism worldwide. It is especially noticeable in the world of healthcare. This article evaluates and highlights examples of antisemitism in four countries by authors from each of these jurisdictions.
When patients undergoing ventral or incisional hernia repair are reoperated for recurrence with an incidence rate of 16.0% following open repair and 18.8% following minimally invasive repair, it is time for re-evaluation of the real benefit of laparoscopy in ventral hernia repair.
