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.     

The risk of fractures,acute myocardial infarction,atrial fibrillation and ventricular arrhythmia in geriatric patients exposed to promethazine

ABSTRACT

Objectives: This study aimed to compare the risk of fractures, acute myocardial infarction, atrial fibrillation, and ventricular arrhythmia among Danish citizens aged ≥ 65 which were new users of promethazine or domperidone, triazolam, loratadine, and betahistine. Secondly, the study aimed to perform a risk stratification to identify the most relevant predictors for the study outcomes.

Methods: The study period was 01/01/2015 to 31/12/2016. The data sources were the Danish registers. Each patient was followed for 90 days. A logistic regression model was used to compute the unadjusted and adjusted odds ratios (OR), and a conditional inference tree was used to identify the most relevant predictors for the study outcomes.

Results: Promethazine had a higher risk of hospitalization for atrial fibrillation than loratadine and betahistine (OR 1.58; 95% CI 1.07–2.63 and OR 3.22; 95% CI 1.69–7.14, respectively). For fractures, acute myocardial infarction, and ventricular arrhythmia hospitalizations, no statistically significant differences were found among drugs under investigation. The medical history of cardiac arrhythmia (OR 4.14; 95% CI 2.94–5.78, p < 0.0001) was the most relevant predictor for atrial fibrillation hospitalizations.

Conclusion: This study found an increased risk of atrial fibrillation hospitalization among promethazine users, and the risk was higher among patients with prior cardiac arrhythmia.     

Results From a Large,Multicenter, Retrospective Analysis On Radium223 Use in Metastatic Castration-resistant Prostate Cancer (mCRPC) in the Triveneto Italian Region

Background

Radium 223 was introduced for metastatic castration-resistant prostate cancer based on the results of a randomized controlled trial showing risk reduction for death and skeletal events. Our aim was to evaluate the outcome of patients receiving radium 223 in a real-world setting.

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.     

Locoregional therapy and systemic cetuximab to treat colorectal liver metastases

AIM: To investigate efficacy and safety of second-line treatment with irinotecan-loaded drug-eluting beads (DEBIRI) and cetuximab (DEBIRITUX) of unresectable colorectal liver metastases.METHODS: Patients with the following characteristics were included in the study: unresectable hepatic metastases from colorectal carcinoma (CRC-LM), progression after first line chemotherapy (any type of chemotherapeutic drug and combination was allowed), second line treatment (mandatory), which included for each patient (unregarding the KRas status) two cycles of DEBIRI (using 100-300 μm beads loaded with irinotecan at a total dose 200 mg) followed by 12 cycles of cetuximab that was administered weekly at a first dose of 400 mg/m² and then 250 mg/m²; good performance status (0-2) and liver functionality (alanine aminotransferase and gamma-glutamyl transferase not exceeding three times the upper limit of normal, total bilirubin not exceeding 2.5 mg/mL). Data were collected retrospectively and included: tumor response (evaluated monthly for 6 mo then every 3 mo), overall response rate (ORR), KRas status, type and intensity of adverse events (G according to the Common Terminology Criteria for Adverse Events v3.0, CTCAE), overall survival (OS) and progression free survival (PFS).RESULTS: Forty consecutive cases of CRC hepatic metastases were included in the study. Median duration of DEBIRITUX was 4.4 mo (range, 4.0-6.5). Sixteen patients (40%) received the planned 2 cycles of DEBIRI and an average of 10 cetuximab cycles. ORR of the whole sample was 50%, in particular 4 patients were complete responders (10%) and 16 (40%) partial responders. The most observed side effects (G2) were: post-embolization syndrome (30%), diarrhea (25%), skin rushes (38%) and asthenia (35%). The retrospective evaluation of KRas status (24 wild type, 16 mutated) showed that the group of patients with wild type KRas had ORR significantly higher than mutant KRas. Median follow-up was 29 mo (8-48 range); median PFS was 9.8 mo and OS was 20.4 mo. Future randomized trials are required in this setting to establish a role for DEBIRITUX compared with systemic chemotherapy.CONCLUSION: DEBIRITUX seems to be efficacious after first line chemotherapy for the treatment of unresectable CRC-LM.     

Innovative immunosuppression in kidney transplantation: A challenge for unmet needs

Due to the optimal results obtained in kidney transplantation and to the lack of interest of the industries, new innovative drugs in kidney transplantation are difficult to be encountered. The best strategy to find the new drugs recently developed or under development is to search in the sections of kidney transplantation still not completely covered by the drugs on the market. These unmet needs are the prevention of delayed graft function (DGF), the protection of the graft over the long time and the desensitization of preformed anti human leukocyte antigen antibodies and the treatment of the acute antibody-mediated rejection. These needs are particularly relevant due to the expansion of some kind of kidney transplantation as transplantation from non-heart beating donor and in the case of antibody-incompatible grafts. The first are particularly exposed to DGF, the latter need a safe desensitization and a safe treatments of the antibody mediated rejections that often occur. Particular caution is needed in treating these drugs. First, they are described in very recent studies and the follow-up of their effect is of course rather short. Second, some of these drugs are still in an early phase of study, even if in well-conducted randomized controlled trials. Particular caution and a careful check need to be used in trials launched 2 or 3 years ago. Indeed, is always necessary to verify whether the study is still going on or whether and why the study itself was abandoned.