Bacterial translocation (BT) may cause infections, in particular, spontaneous bacterial peritonitis (SBP). In the absence of overt infection, BT may further stimulate the immune system and contribute ...to haemodynamic alterations and complications. Bacterial DNA (bDNA) is claimed to be a promising surrogate marker for BT, although its clinical relevance has been questioned.
In 38 cirrhotic patients with and without SBP, bDNA in blood and ascites were assessed by 16S rDNA quantitative PCR. Levels of lipopolysaccharide-binding protein in plasma and highly sensitive C-reactive protein, tumour necrosis factor-α, soluble urokinase plasminogen activating receptor, interleukin-6, interleukin 8, interferon-γ inducible protein-10 and vascular endothelial growth factor in plasma and ascites were measured by multiplex cytokine and ELISA assays.
In patients without signs of SBP or positive cultures, we found a high frequency of bDNA but low concordance of bDNA between blood and ascites. Markers of inflammation were not significantly different between blood bDNA-positive (22%), ascites bDNA-positive (52%), and bDNA-negative patients. The 16S rDNA PCR failed to show bDNA in two out of six samples with SBP. Sequencing of positive samples did not determine the source of bDNA.
bDNA as assessed by this PCR method was largely unrelated to markers of inflammation and does not seem to be of clinical value in the diagnosis of SBP. According to our results, bDNA is not a reliable marker of BT.
A reduced response to aspirin and clopidogrel predicts ischemic events, but reliable tests are needed to identify low responders. We compared 3 platelet-function tests during long-term dual treatment ...with aspirin and clopidogrel.
Patients who underwent a percutaneous coronary intervention and were receiving a combination of 325 mg/day aspirin and 75 mg/day clopidogrel were followed for 1 year. Blood was sampled 5 times during this period for 3 tests: light transmission aggregometry (LTA) assay, with 5.0 micromol/L ADP or 1.0 mmol/L arachidonic acid (AA) used as an agonist; VerifyNow assay, with the P2Y(12) or aspirin cartridge (Accumetrics); and thrombelastography (TEG), stimulated by 2.0 micromol/L ADP or 1.0 mmol/L AA.
Twenty-six of 33 patients completed all scheduled visits. A low response to clopidogrel was found in a few patients at variable frequencies and at different visits, depending on the method and criteria used. We found a moderate correlation between the LTA (ADP) and VerifyNow (P2Y(12) cartridge) results, but the TEG (ADP) results correlated poorly with the LTA and VerifyNow results. A low response to aspirin was found with the VerifyNow (aspirin cartridge) and TEG (AA) methods on 6 and 2 occasions, respectively, but not with the LTA (AA) method, except for 1 occasion caused by probable noncompliance.
Detecting a low response to clopidogrel depends largely on the method used. Which method best predicts ischemic events remains uncertain. A low response to aspirin is rare with AA-dependent methods used at the chosen cutoffs. In some patients, the response to clopidogrel or aspirin may be classified differently at different times, even with the same method.
Introduction
Limited data exist on patient safety after simultaneous vs staged bilateral total knee arthroplasty (TKA) in matched groups. Hence, the aim of this study was to compare length of stay ...(LOS), in-hospital complications, 30-day readmissions and mortality after simultaneous and staged bilateral TKA in matched patients.
Patients and methods
A retrospective case–control study of prospectively collected data in nine centres from February 2010 to November 2015. Propensity scores (PS) were used to match simultaneous and staged (1–6 months between stages) bilateral TKA patients with prospectively collected patient characteristics from the Lundbeck Foundation Centre for Fast-track THA and TKA Database. 30-day follow-up was acquired from the Danish Patient Registry and patient records.
Results
A total of 344 (47.1%) simultaneous and 386 (52.9%) staged bilateral TKA procedures were performed. PS matching was possible in 232 simultaneous and 232 staged bilateral TKA patients. LOS was median 4 days (IQR 3–5) after simultaneous and cumulated 4 days (IQR 4–6) after staged procedures. The in-hospital complication rate was 15.5% after simultaneous vs 7.3% (
p
= 0.004) after staged procedures. Two cases (0.9%) of venous thromboembolic events were found in each group. Eight patients (3.4%) were re-operated after simultaneous vs one patient (0.4%) after staged bilateral TKA (
p
= 0.037). The 30-day readmission rate was 8.6% after simultaneous vs 5.6% after staged procedures (
p
= 0.281). No patients died in either group.
Conclusions
We found no significant differences in 30-day readmission rates and mortality between simultaneous and staged bilateral TKA, but the in-hospital complication rate and re-operation rate was higher after the simultaneous procedure calling for further matched investigations in larger cohorts.
•Colorectal cancer screening using Fecal Immunochemical Test (FIT) reduces both morbidity and mortality.•However, FIT screening is linked to high demand of colonoscopy capacity mainly due to a high ...false positive rate.•In here, we tested whether our proposed algorithm using FIT, blood-based biomarker analysis and demographics of the subject could improve screening.•The algorithm reduced the amount of needed colonoscopies by 4%-11%.
Fecal Immunochemical Test (FIT) is widely used in population-based screening for colorectal cancer (CRC). This had led to major challenges regarding colonoscopy capacity. Methods to maintain high sensitivity without compromising the colonoscopy capacity are needed. This study investigates an algorithm that combines FIT result, blood-based biomarkers associated with CRC, and individual demographics, to triage subjects sent for colonoscopy among a FIT positive (FIT+) screening population and thereby reduce the colonoscopy burden.
From the Danish National Colorectal Cancer Screening Program, 4048 FIT+ (≥100 ng/mL Hemoglobin) subjects were included and analyzed for a panel of 9 cancer-associated biomarkers using the ARCHITECT i2000. Two algorithms were developed: 1) a predefined algorithm based on clinically available biomarkers: FIT, age, CEA, hsCRP and Ferritin; and 2) an exploratory algorithm adding additional biomarkers: TIMP-1, Pepsinogen-2, HE4, CyFra21-1, Galectin-3, B2M and sex to the predefined algorithm. The diagnostic performances for discriminating subjects with or without CRC in the 2 models were benchmarked against the FIT alone using logistic regression modeling.
The discrimination of CRC showed an area under the curve (AUC) of 73.7 (70.5-76.9) for the predefined model, 75.3 (72.1-78.4) for the exploratory model, and 68.9 (65.5-72.2) for FIT alone. Both models performed significantly better (P < .001) than the FIT model. The models were benchmarked vs. FIT at cutoffs of 100, 200, 300, 400, and 500 ng/mL Hemoglobin using corresponding numbers of true positives and false positives. All performance metrics were improved at all cutoffs.
A screening algorithm including a combination of FIT result, blood-based biomarkers and demographics outperforms FIT in discriminating subjects with or without CRC in a screening population with FIT results above 100 ng/mL Hemoglobin.
This study aimed to investigate if a 2-step algorithm using fecal immunochemical test, blood-based biomarkers and demographics of a subject could enhance screening for colorectal cancer. Our results indicate that the algorithm could reduce the number of colonoscopies by up to 11% without compromising colorectal cancer detection.
To evaluate probabilities of disability pension (DP) and premature exit from the workforce (PEW) in patients with stable angina symptoms and no obstructive coronary artery disease (CAD) at ...angiography compared with obstructive CAD and asymptomatic reference individuals.
We followed 4303 patients with no prior cardiovascular disease having a first-time coronary angiography (CAG) in 1998-2009 due to stable angina symptoms and 2772 reference individuals from the Copenhagen City Heart Study, all aged <65 years, through registry linkage until 2009 for DP and PEW. Five-year age-adjusted DP-free survival probabilities for reference individuals, patients with angiographically normal coronary arteries, angiographically diffuse non-obstructive CAD, 1 stenotic coronary vessel (1VD), 2VD, and 3VD, respectively, were 0.96, 0.88, 0.84, 0.82, 0.85, and 0.78 in women and 0.98, 0.90, 0.89, 0.89, 0.88, and 0.87 in men. Significant predictors of DP were higher age, angina symptoms, higher body mass index, diabetes, smoking, job status, non-marital status in men, lower income, lower educational level, and co-morbidity. Compared with the reference population, probabilities of DP and PEW were significantly increased in all patients with no gender difference (P > 0.2 for interaction). Thus, in pooled multivariable-adjusted analysis, patients referred to CAG for angina had a three-fold higher probability of DP and ~50% higher probability of PEW, with little difference between patients with angiographically normal coronary arteries, angiographically diffuse non-obstructive CAD, 1VD, 2VD, 3VD, the hazard ratios for DP being 2.7, 3.0, 3.3, 3.1, and 3.2 (all P < 0.001) and for PEW being 1.3, 1.4, 1.5, 1.6, and 1.6 (all P < 0.05).
Patients with angina symptoms and angiographically normal coronary arteries, diffuse non-obstructive CAD, or obstructive CAD at angiography have a three-fold increased probability of DP regardless of angiographic findings.
ABSTRACT
Introduction
We investigated the effect of high‐intensity exercise on plasma creatine kinase (CK) in patients with muscular dystrophies.
Methods
Fourteen patients with Becker (BMD), ...facioscapulohumeral (FSHD), or limb‐girdle type 2 (LGMD2) muscular dystrophy, and 8 healthy subjects performed 5 cycling tests: an incremental max test, and tests at 65%, 75%, 85%, and 95% of maximal oxygen uptake (VO2max). Heart rate and oxygen consumption were measured during the tests, and plasma CK was measured before, immediately after, and 24 hours after exercise.
Results
All subjects were able to perform high‐intensity exercise at the different levels. In patients with LGMD2 and FSHD, CK normalized 24 hours after exercise compared with the pre‐exercise value, whereas those with BMD and healthy controls had elevated CK values 24 hours after exercise.
Conclusions
The findings suggest that high‐intensity exercise is generally well tolerated in patients with LGMD2 and FSHD, whereas those with BMD may be more prone to exercise‐induced damage. Muscle Nerve 48: 897–901, 2013
Cigarette smoke (CS) is the main cause of chronic obstructive pulmonary disease. Surfactant protein D (SP-D) is an important anti-inflammatory protein that regulates host immune defense in the lungs. ...Here, we investigated the role of SP-D in a murine model of CS-induced inflammation. Pulmonary SP-D localization and abundance was compared between smoker and non-smoker individuals. For
studies, wildtype, and SP-D-deficient mice were exposed to CS for either 12 weeks or 3 days. Moreover, the effect of therapeutic administration of recombinant fragment of human SP-D on the acute CS-induced changes was evaluated. Pulmonary SP-D appeared with heterogenous expression in human smokers, while mouse lung SP-D was uniformly upregulated after CS exposure. We found that SP-D-deficient mice were more susceptible to CS-induced macrophage-rich airway inflammation. SP-D deficiency influenced local pro-inflammatory cytokine levels, with increased CCL3 and interleukin-6 but decreased CXCL1. Furthermore, CS exposure caused significant upregulation of pro-inflammatory ceramides and related ceramide synthase gene transcripts in SP-D-deficient mice compared to wildtype littermates. Administration of recombinant fragment of human SP-D (rfhSP-D) alleviated CS-induced macrophage infiltration and prevented induction of ceramide synthase gene expression. Finally, rfhSP-D treatment attenuated CS-induced human epithelial cell apoptosis
. Our results indicate that SP-D deficiency aggravates CS-induced lung inflammation partly through regulation of ceramide synthesis and that local SP-D enrichment rescues CS-induced inflammation.
Lithium accumulates in the colon and inhibits the enzyme GSK-3β that possesses anti-carcinogenic effects. We therefore examined the association between lithium use and colorectal cancer risk in a ...nationwide study.
We used the Danish Cancer Registry to identify all patients diagnosed with incident colorectal adenocarcinoma during 2000-2012 (n=36 248). Using a matched case-control approach, we estimated the association between long-term use (⩾5 years) of lithium and risk of colorectal adenocarcinoma using conditional logistic regression.
Long-term use of lithium was similar among cases (0.22%) and controls (0.20%), yielding an odds ratio of 1.13 (95% confidence interval (CI), 0.89-1.43) for colorectal adenocarcinoma. Dose-response, subgroup and other subanalyses returned neutral associations. However, ORs differed for colorectal subsites (proximal colon: 1.01 (95% CI, 0.66-1.55; distal colon: 1.52 (95% CI, 1.05-2.20); and rectum: 0.80 (95% CI, 0.50-1.30).
Lithium use was not associated with an overall increased risk of colorectal adenocarcinoma. The variation by subsite warrants further investigation.
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