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Background & Aims: The prevalence and clinical significance of vitamin B12 alterations in patients with cancer are poorly understood. We aimed to assess the prevalence and risk factors of vitamin B12 depletion or hypervitaminosis in patients with cancer., Methods: We retrospectively included hospitalised patients with cancer in 2017-2022. Plasma B12 levels were stratified as very low (VL, <200 pg/ml), low (L, 200-299 pg/ml), normal (N, 300-812 pg/ml), or high (H, ≥813 pg/ml). We collected demographic and several clinical data (e.g., comorbidities, nutritional status, ECOG-PS, cancer site and stage). Univariate and multivariate analyses for factors associated to the vitamin B12 status were fitted., Results: 788 patients (F/M ratio 1.05, median age 72 years, [25th, 75th percentiles 62, 78 years]) were included. Vitamin B12 was VL in 14.1%, L in 19.4%, N in 49.4%, and H in 17.1% cases. Vitamin B12 distribution increased significantly as function of ECOG-PS levels. Patients with breast cancer were characterized by the highest median B12 value, while colorectal cancer patients by the lowest. Vitamin B12 was also significantly higher in advanced compared to early-stage patients as well as in those who had liver failure. Multivariate analysis showed that the probability of H vs. VL B12 levels was significantly increased in patients with hypoproteinemia, hypo-prealbuminemia, and ECOG-PS≥2, and decreased in those with colorectal and gastric cancer., Conclusion: Vitamin B12 impairment is common in cancer patients. Increased vitamin B12 is associated with an impaired clinical status, while vitamin B12 depletion is more common in early-stage cancer and in elderly patients., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Advanced breast cancer (ABC) is characterized by multidimensional clinical complexity that is usually not considered in randomized clinical trials. In the present real-life study, we investigated the link between clinical complexity and quality of life of patients with HR + /HER2 - ABC treated with CDK4/6 inhibitors., Methods: We evaluated multimorbidity burden assessed with the Cumulative Illness Rating Scale (CIRS), polypharmacy and patient-reported outcomes (PROs). PROs were assessed at baseline (T0), after 3 months of therapy (T1), and at disease progression (T2) using EORTC QLC-C30 and QLQ-BR23 questionnaires. Baseline PROs and changes between T0 and T1 were evaluated amongst patients with different multimorbidity burden (CIRS <5 and ≥5) and polypharmacy (<2 or ≥2 drugs)., Results: From January 2018 to January 2022, we enrolled 54 patients (median age 66 years, IQR 59-74). The median CIRS score was 5 (IQR 2-7), whilst the median number of drugs taken by patients was 2 (IQR 0-4). No changes in QLQ-C30 final scoring between T0 and T1 were observed in the overall cohort ( p =0.8944). At T2, QLQ-C30 global score deteriorated with respect to baseline ( p =0.0089). At baseline, patients with CIRS ≥5 had worse constipation than patients without comorbidities ( p <0.05) and a lower trend in the median QLQ-C30 global score. Patients on ≥2 drugs had lower QLQ-C30 final scores and worse insomnia and constipation ( p <0.05). No change in QLQ-C30 final score from T0 to T1 was observed ( p >0.05)., Conclusion: Multimorbidity and polypharmacy increase the clinical complexity of patients with ABC and may affect baseline PROs. The safety profile of CDK4/6 inhibitors seems to be maintained in this population. Further studies are needed to assess clinical complexity in patients with ABC.This article is part of the Tackling clinical complexity in breast cancer Special Issue: https://www.drugsincontext.com/special&#95;issues/tackling-clinical-complexity-in-breast-cancer/., Competing Interests: Disclosure and potential conflicts of interest: The authors declare that they have no conflicts of interest relevant to this article. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2023/05/dic.2023-1-7-COI.pdf, (Copyright © 2023 Tagliaferri B, Mollica L, Palumbo R, Leli C, Malovini A, Terzaghi M, Quaquarini E, Teragni C, Maccarone S, Premoli A, Sottotetti F.)

Background: Comparison of toxicogenomic data facilitates the identification of deregulated gene patterns and maximizes health risk prediction in human., Results: Here, we performed phenotypic anchoring on the effects of acute exposure to low-grade polluted groundwater using mouse and zebrafish. Also, we evaluated two windows of chronic exposure in mouse, starting in utero and at the end of lactation. Bioinformatic analysis of livers microarray data showed that the number of deregulated biofunctions and pathways is higher after acute exposure, compared to the chronic one. It also revealed specific profiles of altered gene expression in all treatments, pointing to stress response/mitochondrial pathways as major players of environmental toxicity. Of note, dysfunction of steroid hormones was also predicted by bioinformatic analysis and verified in both models by traditional approaches, serum estrogens measurement and vitellogenin mRNA determination in mice and zebrafish, respectively., Conclusions: In our report, phenotypic anchoring in two vertebrate model organisms highlights the toxicity of low-grade pollution, with varying susceptibility based on exposure window. The overlay of zebrafish and mice deregulated pathways, more than single genes, is useful in risk identification from chemicals implicated in the observed effects.

Background: Human herpes virus 8 (HHV-8) is the putative infectious agent of multifactorial diseases, such as Kaposi's sarcoma (KS), primary effusion lymphoma and multicentric Castleman's disease. However, its exact mode of action as well as its transmission is still under investigation. Besides, little is known about its seroprevalence in the population. HHV-8 epidemiology has been widely studied all over the world, demonstrating significant differences in distribution among various geographical areas and various population communities. Very few studies of HHV-8 seroprevalence have been conducted in Italy, particularly in Sicily which, along with other Mediterranean areas, is known to have high rates of KS incidence. Between January 2001 and April 2002, 424 patients were consecutively recruited from three treatment facilities. An Infectious Diseases Clinic provided 196 anti-HIV positive patients, both affected by AIDS and not. A further 122 anti-HIV negative intravenous drug users were recruited from drug treatment clinics, while as a control group from the Blood Bank 126 blood donors were recruited. Base-line serum samples were assayed for antibodies to HHV-8 latency-associated nuclear antigen (anti-LANA) by IFA (Viramed Biotech AG, Planneg/Steinkirken--Germany). Anti-HHV-8 antibodies were found in 98 individuals (23.1%). HHV-8 reactivity was more common among anti-HIV positive patients (89/196, 45.4%, 95 C.I. 38.4-52.4) than in IDUs (6/102, 5.9%, 95 C.I. 1.2-16.2) and the control group (3/126, 2.4%, 95 C.I. 0.7-10.1). Overall, anti-HHV-8 antibodies were found in all three groups with large differences between groups.