BACKGROUND Cytokines are polypeptides that constitute a class of chemical mediator molecules that modulate cell growth by inducing specific target gene expression. The objective of this study was to evaluate the clinical usefulness of serum evaluation of the cytokine macrophage migration inhibitory factor (MIF) in patients undergoing routine prostate specific antigen (PSA) screening. METHODS In this preliminary, retrospective study, the authors report the development of an enzyme‐linked immunosorbent assay (ELISA) for MIF determination in serum samples. A polymerase chain reaction (PCR)‐based assay investigated associations between MIF expression and prostate carcinoma (CaP). The authors developed a relative quantitative reverse transcriptase‐PCR assay to determine MIF mRNA amounts within laser‐capture microscopy (LCM)‐dissected prostate epithelial cells. RESULTS A comparison of serum MIF levels and total PSA levels identified a positive correlation (correlation coefficient [r2] = 0.61; P < 0.001; n = 509 patients), suggesting an association between elevated serum concentrations of these proteins and CaP. A correlation of serum MIF levels with a diagnosis of CaP demonstrated that patients with a previous CaP diagnosis had significantly elevated serum MIF concentrations (mean ± standard deviation, 6.8 ± 0.87 ng/mL; P < 0.001). To associate altered serum MIF levels with MIF mRNA expression within prostate epithelial cells, LCM‐dissected prostate epithelial cells (formalin fixed biopsies from three different patients) were used to determine MIF mRNA amounts by PCR analysis. On average, MIF mRNA amounts were 6.5 times higher in CaP epithelial cells that were invasive to the margin compared with MIF mRNA amounts in normal prostate epithelial cells within the same biopsy specimen. CONCLUSIONS The ELISA data from the current study suggested an association between increased MIF expression and CaP and suggested that serum MIF concentration may serve as a prognostic marker for CaP. Cancer 2002;94:1449–56. © 2002 American Cancer Society. DOI 10.1002/cncr.10354

Background: Patients with neuroimmunological conditions such as multiple sclerosis (MS) often receive diseasemodifying therapies (DMTs) or immunosuppressants which may reduce the response to vaccines. BNT162b2 (Pfizer-BioNTech) is the first COVID-19 vaccine authorized in Italy. Its clinical efficacy and serological response were not evaluated in MS patients receiving DMTs or immunosuppressants. This early multicenter study evaluated serological response to BNT162b2 and safety in these patients. Methods: From February 2021 we enrolled consecutive MS patients, treated with at least one DMT and all healthcare workers (HCWs), having received or being scheduled to receive the first dose of BNT162b2. Blood samples were collected after the second vaccine dose and analyzed to quantitatively detect the presence of anti-Spike antibodies. Serological response was compared to the one from a control population of HCWs, with neither neuroimmunological conditions nor receiving immunosuppressants. Patients receiving treatments associated with a possible reduced response (Under-scrutiny treatment group) were also compared to those undergoing other treatments. Anti-Spike levels were described as median and interquartile range (IQR). Comparisons were performed with Wilcoxon-Mann-Whitney test. Solicited and unsolicited adverse events (AEs) were collected. Results: 39 MS patients and a control population of 273 HCWs were included. One patient, under treatment with ocrelizumab, did not respond to BNT162b2, while all the remaining patients and all controls developed a serological response to the vaccine. Median anti-Spike levels were similar between patients (1471.0 BAU/ml; IQR 779.7 to 2357.0) and controls (1479.0 BAU/ml; IQR 813.1 to 2528.0) (p = 0.53). Patients included in the Underscrutiny treatments group showed reduced anti-Spike levels (156.4 BAU/ml; IQR 33.4 to 559.1) compared to those receiving other treatments (1582.4 BAU/ml; IQR 1296.5 to 2219.0) (p = 0.001). Solicited AEs were all mild to moderate in severity, generally reported in the first days after vaccination, and resolved in the following days. Two MS patients reported a clinical relapse after the second vaccine dose. Conclusion: BNT162b2 induced a serological response in MS patients treated with DMTs similar to controls not receiving DMTs or immunosuppressants. Some treatments were associated with reduced levels of anti-Spike antibodies in patients. These observations have relevant implications for treated patients receiving BNT162b2 and the community.

Leber's hereditary optic neuropathy (LHON) is due to missense point mutations affecting mitochondrial DNA (mtDNA); 90% of cases harbor the m.3460G&gt;A, m.11778G&gt;A, and m.14484T&gt;C primary mutations. Here, we report and discuss five families with patients affected by symptomatic LHON, in which we found five novel mtDNA variants. Remarkably, these mtDNA variants are located in complex I genes, though without strong deleterious effect on respiration in cellular models: this finding is likely linked to the tissue specificity of LHON. This study observes that in the case of a strong clinical suspicion of LHON, it is recommended to analyze the whole mtDNA sequence, since new rare mtDNA pathogenic variants causing LHON are increasingly identified.