Immunogenicity of two doses of BNT162b2 and mRNA-1273 vaccines for solid cancer patients on treatment with or without a previous SARS-CoV-2 infection

Previous studies on the immunogenicity of SARS-CoV-2 mRNA vaccines showed a reduced seroconversion in cancer patients. The aim of our study is to evaluate the immunogenicity of two doses of mRNA vaccines in solid cancer patients with or without a previous exposure to the virus. This is a single-institution, prospective, nonrandomized study. Patients in active treatment and a control cohort of healthy people received two doses of BNT162b2 (Comirnaty, BioNTech/Pfizer, The United States) or mRNA-1273 (Spikevax, Moderna). Vaccine was administered before starting anticancer therapy or on the first day of the treatment cycle. SARS-CoV-2 antibody levels against S1, RBD (to evaluate vaccine response) and N proteins (to evaluate previous infection) were measured in plasma before the first dose and 30 days after the second one. From January to June 2021, 195 consecutive cancer patients and 20 healthy controls were enrolled. Thirty-one cancer patients had a previous exposure to SARS-CoV-2. Cancer patients previously exposed to the virus had significantly higher median levels of anti-S1 and anti-RBD IgG, compared to healthy controls (P = .0349) and to cancer patients without a previous infection (P < .001). Vaccine type (anti-S1: P < .0001; anti-RBD: P = .0045), comorbidities (anti-S1: P = .0274; anti-RBD: P = .0048) and the use of G-CSF (anti-S1: P = .0151) negatively affected the antibody response. Conversely, previous exposure to SARS-CoV-2 significantly enhanced the response to vaccination (anti-S1: P < .0001; anti-RBD: P = .0026). Vaccine immunogenicity in cancer patients with a previous exposure to SARS-CoV-2 seems comparable to that of healthy subjects. On the other hand, clinical variables of immune frailty negatively affect humoral immune response to vaccination.     

基于蒙医白脉理论探析帕金森病＊

帕金森病是以多巴胺能神经元减少导致的以静止性震颤、肌强直、运动迟缓和姿势步态障碍为主要临床症状的疾病。此病是蒙医白脉病的一种，又称彻彻热乎病。蒙医将人体的脉络分为白脉和黑脉。白脉病是白脉系统遭受致病因素的影响后所致的一系列疾病的总称，临床上很多疾病归属于“白脉病”。为更好的实现对蒙医优势单病种的规范化研究，本文基于白脉理论，探析蒙医对帕金森病的认识，以期为未来的研究提供理论支持。     

Plasma levels of polychlorinated biphenyls (PCB) and the risk of soft tissue sarcoma

Background::Soft tissue sarcoma (STS) is a heterogeneous group of rare neoplasms whose aetiology is largely unknown. Dioxin and dioxin-like compounds, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and polychlorinated biphenyls (PCBs), are potential risk factors for STS.Objectives:To investigate the relation of 17 PCBs congeners, assessed in human plasma, with STS risk.Methods:We conducted a case-control study in Italy, including 52 STS cases and 99 hospital-based controls. Selected PCB were extracted by high-performance liquid chromatography (HPLC) and measured with gas chromatography-mass spectrometry (GC-MS). Odds ratios (OR), and the corresponding 95% confidence intervals (CI), were estimated through multivariate logistic regression models.Results:The most frequently detected PCB congeners were 138, 170, 180 and 149 (detected in 40-77% of controls). The OR for the sum of all 17 PCB congeners was 1.20 (95% CI 0.50-2.92). In categorical analysis no consistent association was found for individual congeners and for groups based on Wolff’s classification or the degree of chlorination. For continuous estimates, borderline positive associations emerged for Wolff’s groups 2A (OR 1.23, 95% CI 0.97-1.55), 2B (OR 1.34, 95% CI 1.00-1.77, and 3 (OR 1.19, 95% CI 0.96-1.49), for moderately (OR 1.20, 95% CI 0.96-1.51) and highly (OR 1.18, 95% CI 0.99-1.41) chlorinated PCBs, and for congeners 170 (OR 1.26, 95% CI 0.98-1.63), 180 (OR 1.26, 95% CI 0.97-1.64) and 138 (OR 1.45, 95% CI 1.02-2.04).Discussion:Most associations between PCBs and STS risk were not significant, but, given the limited sample size, we cannot exclude moderate associations.Key words: Soft tissue sarcoma, polychlorinated biphenyls, epidemiology, environmental risk factors, chemical contaminants, case-control study     

Insights into the pathogenesis of ATP1A1‐related CMT disease using patient‐specific iPSCs

The development of patient‐specific induced pluripotent stem cells (iPSCs) offered interesting insights in modeling the pathogenesis of Charcot‐Marie‐Tooth (CMT) disease and thus we decided to explore the phenotypes of iPSCs derived from a single CMT patient carrying a mutant ATP1A1 allele (p.Pro600Ala). iPSCs clones generated from CMT and control fibroblasts, were induced to differentiate into neural precursors and then into post‐mitotic neurons. Control iPSCs differentiated into neuronal precursors and then into post‐mitotic neurons within 6‐8 days. On the contrary, the differentiation of CMT iPSCs was clearly defective. Electrophysiological properties confirmed that post‐mitotic neurons were less mature compared to the normal counterpart. The impairment of in vitro differentiation of CMT iPSCs only concerned with the neuronal pathway, because they were able to differentiate into mesendodermal cells and other ectodermal derivatives. ATP1A1 was undetectable in the few neuronal cells derived from CMT iPSCs. ATP1A1 gene mutation (p.Pro600Ala), responsible for a form of axonal CMT disease, is associated in vitro with a dramatic alteration of the differentiation of patient‐derived iPSCs into post‐mitotic neurons. Thus, the defect in neuronal cell development might lead in vivo to a decreased number of mature neurons in ATP1A1‐CMT disease.     

Revues prédatrices : une vraie menace pour la recherche médicale. 2 Evaluer leurs conséquences et engager une riposte

The deleterious consequences of “predatory” journals are numerous, whether the researcher submitted his work to them naively or knowingly: work little or not read by the international community in the absence of indexing and disappearance of any digital trace in the absence of archiving. The reputation of researchers but also of universities and research organizations and the credit of science for citizens can be sustainably damaged. These open access journals, with the author who pays as model, represent as many resources unavailable for legitimate journals. A joint mobilization of all the actors involved is necessary: researchers, universities and faculties of medicine, sections of the national university council, publishers of legitimate journals, research organizations, learned societies, ethics committees, funders, media and political decision-makers. Publishing in a predatory journal is now a scientific misconduct.     

Hormonal and Psychogenic Risk Factors for Erectile Dysfunction in Men with HTLV-1

IntroductionErectile dysfunction (ED) is associated with neurological damage due to human T-lymphotropic virus 1 (HTLV-1) infection, but hormonal and psychogenic factors also cause ED.AimTo evaluate the association of psychogenic and hormonal factors with ED in men infected with HTLV-1.MethodsIn this cross-sectional study, we compared total testosterone, follicle stimulating hormone, luteinizing hormone, prolactin, anxiety symptoms, depressive symptoms, and neurologic manifestations in HTLV-1-infected men with or without ED. The International Index of Erectile Function was used to determine the degree of ED. Participants were grouped according to Osame’s Motor Disability Scale and the Expanded Disability Status Scale: HTLV-1-associated myelopathy or tropical spastic paraparesis (HAM/TSP), probable HAM/TSP, or HTLV-1 carrier. Chi-square and Fisher’s exact tests were used to compare the groups, and regression analyses were used to show predictors of ED.Main Outcome MeasureSexual hormonal levels, psychogenic factors, and neurologic disabilities were found to be associated with ED.ResultsED was associated with age older than 60 years (P < .001), degree of neurologic involvement (P < .001), depression (P = .009), and anxiety (P = .008). In the multivariate analyses, only age and degree of neurological injury remained as risk factors for ED.Clinical ImplicationsNeurological manifestations are a stronger predictor of ED than hormonal and psychogenic factors in HTLV-1-infected men.Strengths & LimitationsThe statistical power of the study was limited due to the low number of participants, but neurologic manifestations were clearly associated with ED. There was no strong association between hormonal and psychogenic factors and ED.ConclusionHormonal and psychogenic factors did not show a strong association with ED in individuals with HTLV-1, but neurological manifestations were strongly associated with ED in these individuals.de Oliveira CJV, Neto, JAC, Andrade RCP, et al. Hormonal and Psychogenic Risk Factors for Erectile Dysfunction in Men with HTLV–1. J Sex Med 2019; 16:1763–1768.     

Perioperative Bevacizumab-based Triplet Chemotherapy in Patients With Potentially Resectable Colorectal Cancer Liver Metastases

Background

In colorectal cancer liver metastases (CRCLM), bevacizumab-based neoadjuvant strategies provide increased pathologic response. We aimed at assessing the activity of perioperative capecitabine, oxaliplatin, irinotecan, and bevacizumab (COI-B regimen) in patients with potentially resectable CRCLM, and investigating biomarkers for early prediction of pathologic response.