Search

Background: Multiple sclerosis (MS) is a chronic central nervous system (CNS) disease, which is diagnosed by a combination of clinical symptoms and magnetic resonance imaging and measurement of an increased intrathecal antibody synthesis. Genetic as well as environmental factors influence onset of the disease, where especially Epstein-Barr virus (EBV) infection is directly involved in MS development. In this open retrospective study, we aimed to elaborate whether various serum and cerebrospinal fluid (CSF)-based EBV antibody indices may aid in the diagnosis of MS., Methods: Epstein-Barr nuclear antigen (EBNA)1 IgG concentrations in serum and CSF of relapsing-remitting (RR)MS patients (n=61) (M:F 28:33, average 40 years), optic neuritis patients (n=26) (M:F 9:17, average 47 years) and healthy controls (HCs) (n=15) (M:F 8:7, average 43 years) were determined by enzyme-linked immunosorbent assay. The obtained EBNA1 IgG levels were compared to factors such as total IgG, albumin concentrations, specific antibody index, and various serum- and CSF-based indices., Results: Significantly elevated EBNA1 IgG levels were detected in serum and CSF of RRMS patients compared to HCs. CSF EBNA1 IgG and indices based on specific CSF EBNA1 IgG associated with CSF albumin or serum EBNA1 IgG associated with total serum IgG obtained the highest sensitivities and complemented the IgG index and oligoclonal bands., Conclusion: These findings indicate that aforementioned indices may supplement existing indices and aid in the diagnosis of MS., Competing Interests: Declaration of competing interest The authors declare no financial or other competing interests related to this work. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2024. Published by Elsevier B.V.)

Background: Graft-versus-host disease (GVHD) is a potentially fatal complication of allogeneic hematopoietic stem cell transplant. The mainstay of treatment is corticosteroids, which are ineffective in 30-50% of cases. Steroid-refractory GVHD (SR-GVHD) confers a poor prognosis, with high mortality rates despite appropriate therapy. While there is no reliable treatment for SR-GVHD, a variety of novel therapeutic options are slowly emerging and have yet to be examined simultaneously., Objectives: This review evaluates the potential of novel therapeutic options, as well as their efficacy and safety, for the treatment of SR-GVHD. Study Design . The literature search was conducted in PubMed, Cochrane, and Embase, employing MeSH terms and keywords. The studies had to be prospective phases 1, 2, or 3. We excluded retrospective and nonoriginal studies., Results: While the only approved drug for acute GVHD is ruxolitinib with an impressive overall response rate of 73.2% and a complete response of 56.3%, several monoclonal antibodies and other agents are currently under investigation, offering promising results. These include anti-CD2, anti-CD147, IL-2 antagonist, a mixture of anti-CD3 and anti-CD7 antibodies, anti-CD25, monoclonal antibody to a4b7 on T-cells, anti-CD26, pentostatin, sirolimus, denileukin diftitox, infliximab, itacitinib, and alpha-1 antitripsin. However, the toxicities associated with these novel drugs need further investigation. For chronic GVHD, approved options include ruxolitinib with an ORR of up to 62%, ibrutinib with an ORR of up to 77%, and belumosudil with an ORR of up to 77%. Meanwhile, emerging treatments include tyrosine kinase inhibitors such as nilotinib, rituximab, and low-dose IL-2, as well as axatilimab and pomalidomide., Conclusion: While their efficacy needs to be better evaluated through large-scale, multicenter, randomized clinical trials, these novel agents show potential and could provide a better alternative for SR-GVHD treatment in the future., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Iuliia Kovalenko et al.)

RET proto-oncogene encodes receptor tyrosine kinase. Selpercatinib and pralsetinib are the only RET-specific tyrosine kinase inhibitors approved by FDA in RET-altered tumors. We searched PubMed, Embase, Cochrane, WOS, and Clinicaltrials.gov. Objective-response, complete-response, and partial-response were 60-89%, 0-11%, and 55-89%, respectively, with the use of RET-specific drugs. ≥Grade 3 adverse events were seen in 28-53% of the patients, with hypertension, change in ALT, QT prolongation, neutropenia, and pneumonitis among the common side effects. Hence, selpercatinib and pralsetinib were effective and well tolerated by most of the patients with RET-altered tumors.

The incidence and prevalence of neuroendocrine neoplasms (NENs) has increased in the US in recent decades. These are well-vascularized tumors, but no antiangiogenic drug has been approved for treatment of extra-pancreatic NENs. The aim is to assess efficacy and safety of surufatinib in pancreatic and extra-pancreatic NETs. We searched PubMed, Embase, Cochrane Library, Web of Science and Clinicaltrials.gov. Clinical trials and observational studies that provided safety and efficacy data in clinical terms were included. Characteristics of the study, baseline characteristics of participants, treatment drugs, measures of efficacy, and toxicity (≥grade 3 adverse effects) were extracted. The meta-analysis was performed using the "R" programming language. Risk ratio (RR) of objective response (OR)/partial response (PR) was 8.55 (95% CI: 1.68-43.66, I 2  = 0) in favor of surufatinib. The hazard ratio (HR) of progression-free survival (PFS) was 0.48 (95% CI: 0.25-0.92, I 2  = 77%) in favor of surufatinib. The risk of ≥grade 3 adverse effects: diarrhea, hypertension, hypertriglyceridemia, proteinuria, and vomiting were high with the use of surufatinib. Quality of life (QoL) was similar in surufatinib and placebo groups except for the diarrhea that was high with surufatinib. Lack of randomized clinical trials in non-Chinese population. Surufatinib is well tolerated and is more effective than placebo in both pancreatic and extra-pancreatic NETs. More multicenter randomized, double-blinded clinical trials are needed to confirm these results., (© 2022 British Society for Neuroendocrinology.)

Background Multiple patients with prostate cancer become resistant to castration therapies, which is termed castration-resistant prostate cancer (CRPC). Purpose The purpose of this review is to assess the status of efficacy (≥50% decline in prostate-specific antigen (PSA), progression-free survival (PFS), and overall survival (OS)) and safety (grade 3-4 adverse effects) of monoclonal antibodies in CRPC. Data source We searched databases including PubMed, Embase, Cochrane, Web of Science, and ClinicalTrials.gov. Results Hazard ratios of PFS and OS were 0.77 (95% CI = 0.69-0.87, I 2  = 53%) and 0.98 (95% CI = 0.86-1.11, I 2  = 40%), respectively, in the favor of monoclonal antibodies as compared to placebo. Risk ratio (RR) of >50% decline in PSA was 1.99 (95% CI = 0.97-4.08, I 2  = 53%) in favor of monoclonal antibodies. Pooled incidence of >50% decline in PSA levels was 15% (95% CI = 0.1-0.23, I 2  = 83%), 29% (95% CI = 0.14-0.51, I 2  = 93%), 63% (95% CI = 0.49-0.76, I 2 = 77%), and 88% (95% CI = 0.81-0.93, I 2  = 0%) in single, two, three, and four-drug regimens, respectively. Conclusion Monoclonal antibodies are well tolerated and showed better PFS as compared to placebo. However, OS was only improved with ipilimumab. Denosumab delayed skeletal-related adverse events as compared to zoledronic acid. More multicenter double-blind clinical trials may be needed to confirm these results., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Tarrar et al.)