Comparison of preoperative continuation and discontinuation of aspirin in patients undergoing total hip or knee arthroplasty

Introduction

Preoperative discontinuation of aspirin (acetylsalicylic acid) can reduce bleeding risk but may increase the risk of perioperative cardiovascular events.

Materials and methods

We retrospectively assessed the impact of preoperative continuation versus discontinuation of aspirin compared with a control group in a cohort of 739 consecutive patients undergoing total hip (THA) (n = 396) or knee arthroplasty (TKA) (n = 343) at a tertiary hospital. Bleeding risk, local complications, orthopaedic outcome, and cardiac and cerebral complications were assessed.

Results

Four hundred and sixty-five patients did not receive antithrombotic or full-dose anticoagulant medication, 175 patients were taking low-dose aspirin, 99 vitamin K antagonists, clopidogrel, or a combination of these drugs. Of the patients taking aspirin, 139 discontinued and 36 continued aspirin. Blood loss and local bleeding complications were comparable in these two groups. TKA patients who continued aspirin more frequently showed marked knee swelling after 1 week than those discontinuing aspirin (35.1 vs. 81.3 %; p = 0.001). However, orthopaedic outcome did not differ significantly between the two groups. There was a trend towards an increased risk of cardiac complications in patients who discontinued aspirin (6.5 vs. 0.0 %; p = 0.107).

Conclusions

Continuation or discontinuation of aspirin did not show a statistically significant difference in the risk of relevant perioperative bleeding complications in our study. Continuation of aspirin was associated with a transitory increase in knee swelling, but had no effect on orthopaedic outcome. Continuation of aspirin may be associated with a favourable perioperative cardiac outcome. Our data support perioperative continuation of aspirin intake in patients undergoing THA or TKA.

     

The Effect of Roux-en-Y Gastric Bypass Surgery in Morbidly Obese Patients on Pharmacokinetics of (Acetyl)Salicylic Acid and Omeprazole: the ERY-PAO Study

Background

Data on the absorption of orally administered drugs following Roux-en-Y gastric bypass (RYGB) surgery in obese patients are limited and inconclusive. As it is difficult to predict changes in absorption, studies on frequently used drugs in this population are necessary. Acetylsalicylic acid (ASA) and omeprazole are two commonly prescribed drugs in obese patients.

Methods

In this repeated measures study, omeprazole and salicylic acid (SA) serum concentrations were measured before and after RYGB in 34 morbidly obese subjects. Time to maximum concentration (Tmax), lag time (Tlag), maximum concentration (Cmax), and area under the serum concentration versus time curve (AUC) were calculated for both drugs to determine possible differences in drug absorption after the procedure.

Results

For SA, Tmax significantly decreased after RYGB, while both Cmax and AUC_0–24 significantly increased. For omeprazole, both Tmax and Tlag significantly decreased after RYGB, while Cmax significantly increased. Mean AUC_0–12 significantly decreased post-surgery. The difference in AUC_0–12 before and after surgery varied between subjects.

Conclusions

Our study shows a faster absorption of both ASA and omeprazole after RYGB. The exposure to ASA is higher post-surgery, but the standard dose of 80 mg does not need to be modified, considering its range in effective dose. The exposure to omeprazole is, on average, decreased after surgery. Clinicians should be aware to increase the dose of omeprazole if symptoms suggest inadequate response.

     

Identification of familial colorectal cancer and hereditary colorectal cancer syndromes through the Dutch population-screening program: results ofa pilot study

Objectives: In 2014, a population-screening program using immuno-faecal occult blood testing (I-FOBT) has started in the Netherlands. The aims of this study were to evaluate the proportion of individuals in the Dutch screening program with a positive I-FOBT that fulfill the criteria for familial colorectal cancer (FCC) and to evaluate the proportion of participants that needs genetic counseling or colonoscopic surveillance.

Material and methods: This retrospective observational study was performed in two large hospitals. Individuals aged between 55 and 75 years with a positive I-FOBT that underwent colonoscopy were included. A detailed family history was obtained in all individuals.

Results: A total of 657 individuals with a positive I-FOBT test underwent colonoscopy. A total of 120 (18.3%) participants were found to have a positive family history for CRC, 20 (3.0%) fulfilled the FCC criteria, 4 (0.6%) the Bethesda guidelines and 1 (0.2%) participant the Amsterdam criteria. Multiple adenomas (>10) were found in 21 (3.2%) participants. No cases of serrated polyposis were identified. Based on these criteria and guidelines, a total of 35 (5.3%) required referral to the clinical geneticist and the relatives of 20 (3.0%) participants should be referred for surveillance colonoscopy.

Conclusion: Obtaining a detailed family history at the time of intake of participants with a positive I-FOBT in the Dutch surveillance program increased the identification of participants with familial CRC.     

Human monoclonal antibodies against anthrax lethal factor and protective antigen act independently to protect against Bacillus anthracis infection and enhance endogenous immunity to anthrax

The unpredictable nature of bioterrorism and the absence of real-time detection systems have highlighted the need for an efficient postexposure therapy for Bacillus anthracis infection. One approach is passive immunization through the administration of antibodies that mitigate the biological action of anthrax toxin. We isolated and characterized two protective fully human monoclonal antibodies with specificity for protective antigen (PA) and lethal factor (LF). These antibodies, designated IQNPA (anti-PA) and IQNLF (anti-LF), were developed as hybridomas from individuals immunized with licensed anthrax vaccine. The effective concentration of IQNPA that neutralized 50% of the toxin in anthrax toxin neutralization assays was 0.3 nM, while 0.1 nM IQNLF neutralized the same amount of toxin. When combined, the antibodies had additive neutralization efficacy. IQNPA binds to domain IV of PA containing the host cell receptor binding site, while IQNLF recognizes domain I containing the PA binding region in LF. A single 180-mug dose of either antibody given to A/J mice 2.5 h before challenge conferred 100% protection against a lethal intraperitoneal spore challenge with 24 50% lethal doses [LD50s] of B. anthracis Sterne and against rechallenge on day 20 with a more aggressive challenge dose of 41 LD50s. Mice treated with either antibody and infected with B. anthracis Sterne developed detectable murine anti-PA and anti-LF immunoglobulin G antibody responses by day 17 that were dependent on which antibody the mice had received. Based on these results, IQNPA and IQNLF act independently during prophylactic anthrax treatment and do not interfere with the establishment of endogenous immunity.     

K-ras mutation detection in colorectal cancer using the Pyrosequencing technique

The identification of gene mutations is a critical goal for the assessment of diagnosis and prognosis in cancer disease, particularly by direct sequencing. Pyrosequencing is a straightforward, non-electrophoretic DNA sequencing method using the luciferase-luciferin light release as a signal for nucleotide incorporation into a PCR template DNA. In this study, we aimed to investigate mutations in the K-ras gene using Pyrosequencing technology, because its reliable chemistry and robust detection mechanism allow for rapid, real-time detection of sequencing events. For the simultaneous detection of the predominant K-ras codons 12 and 13 mutations, we established a sequencing protocol based on the design of a single PCR primer pair and a single sequencing primer. The assay has been validated with DNA from 65 colorectal carcinomas. Furthermore, analysis of the rare K-ras codon 61 mutation was included. In 29% (19/65) of the patients, the K-ras gene was found to be mutated, whereas codons 12 and 13 were most frequently affected (18/65, 27.7%). Mutations with the highest frequency were G-->A transitions (12/19, 63%), followed by G-->T transversions (5/19, 26%). Overall survival was significantly shorter in patients with a tumor containing K-ras codon 12 mutations than in those without K-ras codon 12 mutations (p=0.024). In conclusion, we found Pyrosequencing to be a suitable technology for fast detection of hot-spot mutations in the K-ras oncogene. We demonstrated an important relationship between K-ras codon 12 mutations and overall survival in colorectal cancer patients.     

No association of chromatin-modifying protein 2B with sporadic frontotemporal dementia

Mutations of the chromatin modifying protein 2B gene (CHMP2B) were identified, in a Danish pedigree, to cause familial frontotemporal dementia (FTD). To explore the possible genetic contribution of common CHMP2B variants in sporadic FTD, we analyzed 14 single nucleotide polymorphisms covering the entire genomic region of CHMP2B. After adjustment for multiple testing single marker and haplotype analysis revealed no significant association with sporadic FTD. Thus, we conclude that CHMP2B can be excluded as a susceptibility gene conferring risk to sporadic forms of FTD.     

Age-dependent cognitive decline and amygdala pathology in alpha-synuclein transgenic mice

Intraneuronal alpha-synuclein (alphaSYN) inclusions constitute the hallmark lesions of a number of neurodegenerative diseases, including Parkinson's disease and dementia with Lewy bodies. In a transgenic mouse model expressing mutant [A30P]alphaSYN under control of the pan-neuronal Thy1 promoter, motor impairment became significant beyond 17 months of age. Cognitive performance was measured in the Morris water maze and upon fear conditioning. At 4 months of age, transgenic mice performed like controls. However, performance in these tasks was significantly impaired in (Thy1)-h[A30P]alphaSYN mice at 12 months of age. After completion of the cognition tests, mice were sacrificed and the regional distribution of neuropathology was examined. In contrast to 4 months old animals, 12 months old transgenic mice showed alpha-synucleinopathy in several brain regions, including the central nucleus of the amygdala, which is involved in cognitive behavior of mice, and is susceptible to alphaSYN pathology in human patients. Thus, age-dependent fibrillization of alphaSYN in specific cortical regions concomitant with cognitive decline may reflect dementia with Lewy bodies in a transgenic mouse model.