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1.
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.  相似文献   
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Data about treatment outcomes and toxicity in Latin America are scarce. There are differences with central countries based on access to healthcare system and socioeconomic status. Argentinean Society of Hematology recommends bortezomib-based triplets for induction treatment of transplant eligible newly diagnosed multiple myeloma patients. Most common options are CyBorD (cyclophosphamide, bortezomib and dexamethasone) and VTD (bortezomib, thalidomide and dexamethasone). Main goal of our retrospective, multicentric study was to compare very good partial response rate (VGPR) or better after induction treatment in a real-world setting in Argentina. Secondary objectives included comparison of complete response (CR) post-induction and after bone marrow transplantation, grade 3-4 adverse events (AEs), progression-free survival (PFS) and overall survival (OS). Three hundred twenty-two patients were included (median age at diagnosis: 57 years; 52% male; 28% had ISS3; 14% with high-risk cytogenetics; median follow up: 34 months). CyBorD was indicated in 74% and 26% received VTD. In VTD arm, 72.62% of patients achieved at least VGPR vs 53.36% receiving CyBorD (odds ratio, OR: 1.96 [95% confidence interval, CI: 1.08-3.57; P = .026] after adjusting by age, ISS [International Staging System], lactate dehydrogenase levels (LDH) and cytogenetic risk. Difference in VGPR was 19.26% (95% CI: 15-24). CR rate were 35.92% (VTD) vs 22.55% (CyBorD) (adjusted OR: 2.13 [95% CI: 1.12-4.05]). Difference in CR was 13.37% (95% CI: 9.6-17.53). Adverse events (AEs) were more common with VTD (69.05% vs 55.46% for CyBorD; P = .030), especially grade 3-4 neuropathy (P = .005) and thrombosis (P = .001). Thromboprophylaxis was inadequate in 20.24% of patients. Hematological AEs were more common with CyBorD, especially thrombocytopenia (P = .017). PFS and OS at 24 months were not different between treatments. In this real-world setting, VTD was associated with better CR and VGPR than CyBorD. Nevertheless, CyBorD continues to be the preferred induction regimen in Argentina, based on safety profile. Frontline autologous stem cell transplantation improves quality of responses, especially in countries with limited access to new drugs.  相似文献   
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Background:Risk behaviors are frequent among young adults and they are particularly relevant when considering healthcare students.Objectives:The study is aimed to examine the prevalence of smoking, binge drinking, physical inactivity, and excessive bodyweight in a population of healthcare students attending an Italian university.Methods:Healthcare students filled an anonymous multiple-choice questionnaire on the occasion of the occupational health visit that preceded their hospital internship. The questionnaire covered socio-demographic characteristics (including student’s working status and cohabitation) and risk behaviors. We evaluated the prevalence of risk behaviors and their association with socio-demographic characteristics.Results:The sample consisted of 494 students (65% women): 23.2% were smokers, 7.9% had excessive bodyweight, 35% did not practice any physical activity and 50% reported binge drinking at least once in the last 12 months. We found associations of male sex (30.5%) and being nursing students (29.9%) with smoking habit. The frequency of binge drinking was higher in men (38.4%), working students (53.9%), and among those who lived without family (50%). Physical inactivity was associated with female sex (44.2%) and living without family (57.1%). Finally, the co-presence of 2 risk behaviors or more was higher in men (36.8%), in nursing students (39.6%) and in working students (44.7%).Conclusions:Our findings regarding the prevalence of risk behaviors and their potential association with socio-demographic factors may be a clue to the definition of targeted strategies aimed at reducing of risk behaviors among healthcare students.Key words: risk behaviors, healthcare students, smoking, binge drinking, physical inactivity  相似文献   
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Background

The conventional chemotherapy of colorectal cancer with irinotecan, 5-fluorouracil, and oxaliplatin remains one of the front-line treatments worldwide. However, its efficacy is quite low. Recently studies of the epithelial–mesenchymal transition (EMT) have become the focus of investigations into the cause of chemoresistance in several types of cancer, including colorectal cancer. The data about the role of EMT in chemosensitivity are controversial.

Materials and Methods

Human colon adenocarcinoma cell lines HT29 and HCT116 and 14 primary short-term cultures established from patient tumors were used. The chemosensitivity to irinotecan, 5-fluorouracil, and oxaliplatin was assessed using the (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Immunocytochemistry, immunohistochemistry, and Western blot test were used to investigate the E-cadherin expression, the loss of which is a major hallmark of EMT.

Results

Elevated chemosensitivity of the cell line with EMT phenotype, HCT116, was demonstrated. Increased chemosensitivity was revealed in HT29 cell line upon EMT induction. E-cadherin–positive short-term cultures were more resistant to all the drugs tested, whereas each of E-cadherin–negative cultures showed sensitivity to at least one drug. The statistically significant dependency of cells viability on the E-cadherin expression (P < .04) was demonstrated on the short-term cultures using 2 concentrations of each drug.

Conclusion

The data obtained may serve as a basis for the analysis of colon cancer chemosensitivity using short-term cultures and the assay of E-cadherin expression.  相似文献   
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Chronic kidney disease (CKD) is one of the most common complications of type 2 diabetes mellitus (T2DM). Furthermore, CKD confers a considerable increase in the risk of cardiovascular (CV) morbidity and mortality. In line with the need to improve knowledge in this field, this article aims to describe the renal endpoints used in the different cardiovascular outcome trials (CVOTs). The objective is to better know the renal variables used in the different CVOTs in order to optimize the implementation of advances in the prevention of progressive diabetic kidney disease in patients with T2DM in clinical practice.  相似文献   
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Measurement of P-selectin on activated platelets as a means of measuring platelet function utilizing the technology described here has the advantage of not requiring immediate access to specialist equipment and expertise. Blood samples are activated, fixed, stored, and transported to a central laboratory for flow cytometric analysis. Here we have compared P-selectin with other more traditional approaches to measuring platelet function in blood and/or platelet-rich plasma (PRP) from patients with acute coronary syndromes on treatment for at least 1 month with either aspirin and clopidogrel or aspirin with prasugrel. The comparators were light transmission aggregometry (LTA), VerifyNow and Multiplate aggregometry (for determining the effects of aspirin) and LTA, VerifyNow and Multiplate together with the BioCytex VASP phosphorylation assay (for the P2Y12 antagonists). The P-selectin Aspirin Test revealed substantial inhibition of platelet function in all but three of 96 patients receiving aspirin with clopidogrel and in none of 51 patients receiving aspirin and prasugrel. The results were very similar to those obtained using LTA. There was only one patient with high residual platelet aggregation and low P-selectin expression. The same patients identified as “non-responders” to aspirin also presented with the highest residual platelet activity as measured using the VerifyNow system, although not quite as well separated from the other values. With the Multiplate test only one of these patients clearly stood out from the others. The results obtained using the P-selectin P2Y12 Test in 102 patients taking aspirin and clopidogrel were similar to the more traditional approaches in that a wide scatter of results was obtained. Generally, high values seen with the P-selectin P2Y12 Test were also high with the LTA, VerifyNow, Multiplate, and BioCytex VASP P2Y12 Tests. Similarly, low residual platelet function using the P2Y12 test was seen irrespective of the testing procedure used. However, there were differences in some patients. Prasugrel was always more effective than clopidogrel in inhibiting platelet function with none of 56 patients (P-selectin and VerifyNow), only 2 of 56 patients (Multiplate) and only 3 of 56 patients (Biocytex VASP) demonstrating high on-treatment residual platelet reactivity (HRPR) defined using previously published cut-off values. The exception was LTA where there were 11 of 56 patients with HRPR. It remains to be seen which experimental approach provides the most useful information regarding outcomes after adjusting therapies in treated patients.  相似文献   
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