Antibodies against p53 are associated with poor prognosis of colorectal cancer.

Mutation of the p53 gene is a common event in colorectal cancer. This alteration can result in cellular accumulation of p53 and may also induce p53 antibodies. Accumulation of p53 in tumour cells has been associated with poor prognosis of colorectal cancer. We tested preoperative sera from 255 patients with colorectal cancer by enzyme-linked immunosorbent assay (ELISA). A total of 70.2% had reactivity that was higher than the 'low' control serum. Employing a cut-off level of 10% of the 'high' control sample, 25.5% of the patients were positive for p53 antibodies. The presence of p53 antibodies correlated with the following prognostic factors: histological differentiation grade, shape of the tumour, and tumour invasion into blood vessels. Patients with p53 antibodies were shown to have decreased survival and decreased disease-free survival. Specifically for patients with cancer stage A and B1 the presence of p53 antibodies selected a subgroup with poor prognosis

HLA-matched platelet transfusions are effective only in refractory patients with positive HLA antibody screening

BACKGROUND Recipients of platelet transfusions with 1-hour corrected count increments (1hCCIs) of 7.5 or less on two subsequent platelet transfusions with random platelets may benefit from human leukocyte antigen (HLA)-matched platelet concentrates. We aimed to quantify the efficacy of HLA-matched platelets concentrates expressed in 1hCCIs. METHODS We performed a cohort study among consecutive refractory patients who received HLA-matched platelet concentrates in the Netherlands between 1994 and 2017. We performed mixed-model linear regression comparing 1hCCIs after HLA split-antigen-matched transfusions with 1hCCIs after HLA-mismatched transfusions, adjusted for within-patient correlations. A donor-to-patient match was categorized as a split-match if all donor HLA-A and -B antigens were present in the patient as well; that is, donor and patient were HLA identical or compatible. Subgroup analyses were performed for patients with positive or negative HLA antibody screens. Finally, the additional effect of ABO mismatches on 1hCCIs was investigated. RESULTS The 1hCCI after an HLA-matched transfusion was 14.09 (95% reference interval, 1.13-29.89). This was 1.94 (95% confidence interval [CI], 0.74-3.15) higher than 1hCCI after HLA-mismatched transfusions. In patients with negative HLA antibody screening tests, HLA matching did not affect 1hCCIs. Conditional on HLA matching, 1hCCIs decreased by 3.70 (95% CI, -5.22 to -2.18) with major ABO mismatches. CONCLUSION Matched platelet concentrates yielded maximal 1hCCIs, whereas mismatched transfusions still resulted in adequate increments. There is no indication for HLA-matched platelets in patients with negative antibody screens

What is case management in palliative care? An expert panel study

Contains fulltext : 110207.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Case management is a heterogeneous concept of care that consists of assessment, planning, implementing, coordinating, monitoring, and evaluating the options and services required to meet the client's health and service needs. This paper describes the result of an expert panel procedure to gain insight into the aims and characteristics of case management in palliative care in the Netherlands. METHODS: A modified version of the RAND(R)/University of California at Los Angeles (UCLA) appropriateness method was used to formulate and rate a list of aims and characteristics of case management in palliative care. A total of 76 health care professionals, researchers and policy makers were invited to join the expert panel, of which 61% participated in at least one round. RESULTS: Nine out of ten aims of case management were met with agreement. The most important areas of disagreement with regard to characteristics of case management were hands-on nursing care by the case manager, target group of case management, performance of other tasks besides case management and accessibility of the case manager. CONCLUSIONS: Although aims are agreed upon, case management in palliative care shows a high level of variability in implementation choices. Case management should aim at maintaining continuity of care to ensure that patients and those close to them experience care as personalised, coherent and consistent

Sex differences in cardiovascular complications and mortality in hospital patients with covid-19: registry based observational study

Objective To assess whether the risk of cardiovascular complications of covid-19 differ between the sexes and to determine whether any sex differences in risk are reduced in individuals with pre-existing cardiovascular disease. Design Registry based observational study. Setting 74 hospitals across 13 countries (eight European) participating in CAPACITY-COVID (Cardiac complicAtions in Patients With SARS Corona vIrus 2 regisTrY), from March 2020 to May 2021 Participants All adults (aged ≥18 years), predominantly European, admitted to hospital with highly suspected covid-19 disease or covid-19 disease confirmed by positive laboratory test results (n=11 167 patients). Main outcome measures Any cardiovascular complication during admission to hospital. Secondary outcomes were in-hospital mortality and individual cardiovascular complications with ≥20 events for each sex. Logistic regression was used to examine sex differences in the risk of cardiovascular outcomes, overall and grouped by pre-existing cardiovascular disease. Results Of 11 167 adults (median age 68 years, 40% female participants) included, 3423 (36% of whom were female participants) had pre-existing cardiovascular disease. In both sexes, the most common cardiovascular complications were supraventricular tachycardias (4% of female participants, 6% of male participants), pulmonary embolism (3% and 5%), and heart failure (decompensated or de novo) (2% in both sexes). After adjusting for age, ethnic group, pre-existing cardiovascular disease, and risk factors for cardiovascular disease, female individuals were less likely than male individuals to have a cardiovascular complication (odds ratio 0.72, 95% confidence interval 0.64 to 0.80) or die (0.65, 0.59 to 0.72). Differences between the sexes were not modified by pre-existing cardiovascular disease; for the primary outcome, the female-to-male ratio of the odds ratio in those without, compared with those with, pre-existing cardiovascular disease was 0.84 (0.67 to 1.07). Conclusions In patients admitted to hospital for covid-19, female participants were less likely than male participants to have a cardiovascular complication. The differences between the sexes could not be attributed to the lower prevalence of pre-existing cardiovascular disease in female individuals. The reasons for this advantage in female individuals requires further research

Does a Platelet Transfusion Independently Affect Bleeding and Adverse Outcomes in Cardiac Surgery?

Background: Conflicting results have been reported concerning the effect of platelet transfusion on several outcomes. The aim of this study was to assess the independent effect of a single early intraoperative platelet transfusion on bleeding and adverse outcomes in cardiac surgery patients. Methods: For this observational study, 23,860 cardiac surgery patients were analyzed. Patients who received one early (shortly after cardiopulmonary bypass while still in the operating room) platelet transfusion, and no other transfusions, were defined as the intervention group. By matching the intervention group 1: 3 to patients who received no early transfusion with most comparable propensity scores, the reference group was identified. Results: The intervention group comprised 169 patients and the reference group 507. No difference between the groups was observed concerning reinterventions, thromboembolic complications, infections, organ failure, and mortality. However, patients in the intervention group experienced less blood loss and required vasoactive medication 139 of 169 (82%) versus 370 of 507 (74%; odds ratio, 1.65; 95% CI, 1.05 to 2.58), prolonged mechanical ventilation 92 of 169 (54%) versus 226 of 507 (45%; odds ratio, 1.47; 94% CI, 1.03 to 2.11), prolonged intensive care 95 of 169 (56%) versus 240 of 507 (46%; odds ratio, 1.49; 95% CI, 1.04 to 2.12), erythrocytes 75 of 169 (44%) versus 145 of 507 (34%; odds ratio, 1.55; 95% CI, 1.08 to 2.23), plasma 29 of 169 (17%) versus 23 of 507 (7.3%; odds ratio, 2.63; 95% CI, 1.50-4.63), and platelets 72 of 169 (43%) versus 25 of 507 (4.3%; odds ratio, 16.4; 95% CI, 9.3-28.9) more often compared to the reference group. Conclusions: In this retrospective analysis, cardiac surgery patients receiving platelet transfusion in the operating room experienced less blood loss and more often required vasoactive medication, prolonged ventilation, prolonged intensive care, and blood products postoperatively. However, early platelet transfusion was not associated with reinterventions, thromboembolic complications, infections, organ failure, or mortality

Immunoassay for quantification of antigen-specific IgG fucosylation

Background Immunoglobulin G (IgG) antibodies serve a crucial immuno-protective function mediated by IgG Fc receptors (Fc gamma R). Absence of fucose on the highly conserved N-linked glycan in the IgG Fc domain strongly enhances IgG binding and activation of myeloid and natural killer (NK) cell Fc gamma Rs. Although afucosylated IgG can provide increased protection (malaria and HIV), it also boosts immunopathologies in alloimmune diseases, COVID-19 and dengue fever. Quantifying IgG fucosylation currently requires sophisticated methods such as liquid chromatography-mass spectrometry (LC-MS) and extensive analytical skills reserved to highly specialized laboratories. Methods Here, we introduce the Fucose-sensitive Enzyme-linked immunosorbent assay (ELISA) for Antigen-Specific IgG (FEASI), an immunoassay capable of simultaneously quantitating and qualitatively determining IgG responses. FEASI is a two-tier immunoassay; the first assay is used to quantify antigen-specific IgG (IgG ELISA), while the second gives Fc gamma RIIIa binding-dependent readout which is highly sensitive to both the IgG quantity and the IgG Fc fucosylation (Fc gamma R-IgG ELISA). Findings IgG Fc fucosylation levels, independently determined by LC-MS and FEASI, in COVID-19 responses to the spike (S) antigen, correlated very strongly by simple linear regression (R-2=0.93, p < 0.0001). The FEASI method was then used to quantify IgG levels and fucosylation in COVID-19 convalescent plasma which was independently validated by LC-MS. Interpretation FEASI can be reliably implemented to measure relative and absolute IgG Fc fucosylation and quantify binding of antigen-specific IgG to Fc gamma R in a high-throughput manner accessible to all diagnostic and research laboratories. Copyright (c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Proteomic

Age is the main determinant of COVID-19 related in-hospital mortality with minimal impact of pre-existing comorbidities, a retrospective cohort study

Background: Age and comorbidities increase COVID-19 related in-hospital mortality risk, but the extent by which comorbidities mediate the impact of age remains unknown. Methods: In this multicenter retrospective cohort study with data from 45 Dutch hospitals, 4806 proven COVID-19 patients hospitalized in Dutch hospitals (between February and July 2020) from the CAPACITY-COVID registry were included (age 69[58–77]years, 64% men). The primary outcome was defined as a combination of in-hospital mortality or discharge with palliative care. Logistic regression analysis was performed to analyze the associations between sex, age, and comorbidities with the primary outcome. The effect of comorbidities on the relation of age with the primary outcome was evaluated using mediation analysis. Results: In-hospital COVID-19 related mortality occurred in 1108 (23%) patients, 836 (76%) were aged ≥70 years (70+). Both age 70+ and female sex were univariably associated with outcome (odds ratio [OR]4.68, 95%confidence interval [4.02–5.45], OR0.68[0.59–0.79], respectively;both p< 0.001). All comorbidities were univariably associated with outcome (p<0.001), and all but dyslipidemia remained significant after adjustment for age70+ and sex. The impact of comorbidities was attenuated after age-spline adjustment, only leaving female sex, diabetes mellitus (DM), chronic kidney disease (CKD), and chronic pulmonary obstructive disease (COPD) significantly associated (female OR0.65[0.55–0.75], DM OR1.47[1.26–1.72], CKD OR1.61[1.32–1.97], COPD OR1.30[1.07–1.59]). Pre-existing comorbidities in older patients negligibly (<6% in all comorbidities) mediated the association between higher age and outcome. Conclusions: Age is the main determinant of COVID-19 related in-hospital mortality, with negligible mediation effect of pre-existing comorbidities. Trial registration: CAPACITY-COVID (NCT04325412)