Determining the stage of non-small-cell lung cancer often requires multiple preoperative tests and invasive procedures. Whole-body positron-emission tomography (PET) may simplify and improve the ...evaluation of patients with this tumor.
We prospectively compared the ability of a standard approach to staging (computed tomography CT, ultrasonography, bone scanning, and, when indicated, needle biopsies) and one involving PET to detect metastases in mediastinal lymph nodes and at distant sites in 102 patients with resectable non-small-cell lung cancer. The presence of mediastinal metastatic disease was confirmed histopathologically. Distant metastases that were detected by PET were further evaluated by standard imaging tests and biopsies. Patients were followed postoperatively for six months by standard methods to detect occult metastases. Logistic-regression analysis was used to evaluate the ability of PET and CT to identify malignant mediastinal lymph nodes.
The sensitivity and specificity of PET for the detection of mediastinal metastases were 91 percent (95 percent confidence interval, 81 to 100 percent) and 86 percent (95 percent confidence interval, 78 to 94 percent), respectively. The corresponding values for CT were 75 percent (95 percent confidence interval, 60 to 90 percent) and 66 percent (95 percent confidence interval, 55 to 77 percent). When the results of PET and CT were adjusted for each other, only PET results were positively correlated with the histopathological findings in mediastinal lymph nodes (P<0.001). PET identified distant metastases that had not been found by standard methods in 11 of 102 patients. The sensitivity and specificity of PET for the detection of both mediastinal and distant metastatic disease were 95 percent (95 percent confidence interval, 88 to 100 percent) and 83 percent (95 percent confidence interval, 74 to 92 percent), respectively. The use of PET to identify the stage of the disease resulted in a different stage from the one determined by standard methods in 62 patients: the stage was lowered in 20 and raised in 42.
PET improves the rate of detection of local and distant metastases in patients with non-small-cell lung cancer.
It is unclear whether cemented or uncemented hemiarthroplasty is the best treatment option in elderly patients with displaced femoral neck fractures. Previous randomized trials comparing cemented and ...uncemented hemiarthroplasty have conflicting results. We conducted a randomized controlled trial to compare cemented and uncemented hemiarthroplasty.
This multicenter parallel-randomized controlled trial included patients of 70 years and older with a displaced femoral neck fracture (Garden type III or IV). Inclusion was between August 2008 and June 2012. Patients were randomized between a cemented hemiarthroplasty, type Müller Straight Stem or an uncemented hemiarthroplasty, type DB-10. Primary outcomes were complications, operation time, functional outcome (measured by Timed-Up-and-Go (TUG) and Groningen Activity Restriction Scale (GARS)) and mid-thigh pain. Health Related Quality of Life (HRQoL, expressed with the SF-12) was measured as an secondary outcome. Follow up was 1 year.
In total 201 patients were included in the study (91 uncemented, 110 cemented hemiarthroplasties) The uncemented group showed more major local complications (intra- and postoperative fractures and dislocations) odds ratio (95% confidence interval) 3.36 (1.40 to 8.11). There was no difference in mean operation time (57.3 vs 55.4 min). There were no differences in functional outcomes (TUG 12.8 (9.4) vs. 13.9 (9.0), GARS 43.2 (19.7) vs. 39.2 (16.5)) and mid-thigh pain (18.6 vs 21.6%). Physical component SF-12 HRQoLwas lower in the uncemented group (30.3 vs. 35.3 p < 0.05 after six weeks, 33.8 vs 38.5 p < 0.05 after 12 weeks).
A cemented hemiarthroplasty in elderly patients with a displaced femoral neck fracture results in less complications compared to an uncemented hemiarthroplasty.
Netherlands Trial Registry; NTR 1508 , accepted date 27 okt 2008.
Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been proposed as (adjuvant) treatment for major depressive disorder (MDD). In the present meta-analysis, we pooled randomized ...placebo-controlled trials assessing the effects of omega-3 PUFA supplementation on depressive symptoms in MDD. Moreover, we performed meta-regression to test whether supplementation effects depended on eicosapentaenoic acid (EPA) or docosahexaenoic acid dose, their ratio, study duration, participants' age, percentage antidepressant users, baseline MDD symptom severity, publication year and study quality. To limit heterogeneity, we only included studies in adult patients with MDD assessed using standardized clinical interviews, and excluded studies that specifically studied perinatal/perimenopausal or comorbid MDD. Our PubMED/EMBASE search resulted in 1955 articles, from which we included 13 studies providing 1233 participants. After taking potential publication bias into account, meta-analysis showed an overall beneficial effect of omega-3 PUFAs on depressive symptoms in MDD (standardized mean difference=0.398 (0.114-0.682), P=0.006, random-effects model). As an explanation for significant heterogeneity (I(2)=73.36, P<0.001), meta-regression showed that higher EPA dose (β=0.00037 (0.00009-0.00065), P=0.009), higher percentage antidepressant users (β=0.0058 (0.00017-0.01144), P=0.044) and earlier publication year (β=-0.0735 (-0.143 to 0.004), P=0.04) were significantly associated with better outcome for PUFA supplementation. Additional sensitivity analyses were performed. In conclusion, present meta-analysis suggested a beneficial overall effect of omega-3 PUFA supplementation in MDD patients, especially for higher doses of EPA and in participants taking antidepressants. Future precision medicine trials should establish whether possible interactions between EPA and antidepressants could provide targets to improve antidepressant response and its prediction. Furthermore, potential long-term biochemical side effects of high-dosed add-on EPA supplementation should be carefully monitored.
After lung transplantation (LTx) exercise capacity frequently remains limited, despite significantly improved pulmonary function. The aim of this study was to evaluate maximal exercise capacity and ...peripheral muscle force before and 1 year after LTx, and to determine whether peripheral muscle force and lactate threshold (LT) limit exercise capacity 1 year after LTx.
Twenty-five subjects (mean age 43 years, 8 women and 17 men, 4 single-lung transplantations) were included in the study. Measurements included maximal exercise capacity, lactate threshold (symptom-limited bicycle ergometer test) and muscle force test (hand-held dynamometer) were performed before and 1 year after LTx.
Before LTx, all patients showed severe exercise intolerance (mean +/- SD): work capacity (W(peak)), 11.6 +/- 18 W; peak oxygen uptake (Vo(2)), 8.6 +/- 3.6 ml/min/kg. After LTx, exercise capacity improved significantly: W(peak), 69 +/- 27 W (p < 0.001); peak Vo(2), 15.7 +/- 4.3 ml/min/kg (p < 0.001). Ventilatory factors did not appear to limit exercise capacity. Quadriceps muscle force pre- vs post-LTx was: 248 +/- 73 N vs 281 +/- 68 N (p < 0.05). Post-LTx, a significant correlation was found between LT and exercise capacity (r = 0.76, p < 0.001), between muscle force and exercise capacity (r = 0.41, p < 0.05) and between the LT and muscle force (r = 0.53, p < 0.01).
The occurrence of an early and pathologic LT and peripheral muscle weakness contributes to the limitation of exercise capacity and reflects a peripheral deficit post-LTx.
Summary
Background There is a large variability in clinical response to corticosteroid treatment in patients with asthma. Several markers of inflammation like eosinophils and eosinophil cationic ...protein (ECP), as well as exhaled nitric oxide (NO), are good candidates to predict clinical response.
Aim We wanted to determine whether we could actually predict a favourable response to inhaled corticosteroids in individual patients.
Methods One hundred and twenty patients with unstable asthma were treated with either prednisolone 30 mg/day, fluticasone propionate 1000 µg/day b.i.d. or fluticasone propionate 250 µg/day b.i.d., both via Diskhaler. They were treated during 2 weeks, in a double‐blind, parallel group, double dummy design. We measured eosinophils and ECP in blood and sputum, and exhaled nitric oxide as inflammatory parameters before and after 2 weeks in order to predict the changes in forced expiratory volume in 1 s (FEV1), provocative concentration of methacholine causing a 20% fall in FEV1 (PC20 Mch), and asthma quality of life (QOL). Secondly, to test whether these results were applicable in clinical practice we determined the individual prediction of corticosteroid response.
Results We found that changes in FEV1, PC20 Mch and QOL with corticosteroids were predominantly predicted by their respective baseline value and to a smaller extent by eosinophils in blood or sputum. ECP, measured in blood or sputum, was certainly not better than eosinophils in predicting clinical response to corticosteroids. Smoking status was an additional predictor for change in FEV1, but not for change in PC20 Mch or QOL. Prediction of a good clinical response was poor. For instance, high sputum eosinophils (≥ 3%) correctly predicted an improvement in PC20 Mch in only 65% of the patients.
Conclusion Our findings show that baseline values of the clinical parameters used as outcome parameters are the major predictors of clinical response to corticosteroids. Eosinophil percentage in blood or sputum adds to this, whereas ECP provides no additional information. Correct prediction of clinical response in an individual patient, however, remains poor with our currently used clinical and inflammatory parameters.
BACKGROUND Inflammatory changes in the airways in chronic obstructive pulmonary disease (COPD) are largely attributed to smoking, yet they may be present even if patients do not currently smoke. The ...differences in inflammatory cells and the factors contributing to these differences were examined in the airways of patients with COPD who do not currently smoke. METHODS Eighteen non-atopic subjects with COPD (14 men) of mean (SD) age 62 (8) years and forced expiratory volume in one second (FEV1) 59 (13)% predicted and 11 non-atopic healthy subjects (eight men) of mean (SD) age 58 (8) years, FEV1 104 (11)% predicted were studied. Sputum induction and bronchoscopy with bronchoalveolar lavage (BAL) and biopsies were performed. RESULTS Patients with COPD had more mucosal EG2+ cells (eosinophils) (median (range) 40 (0–190) versus 5 (0–40) cells/mm2, p = 0.049) and CD68+ cells (1115 (330–2920) versus 590 (450–1580) cells/mm2, p = 0.03), and a tendency towards more CD4+ but not CD8+ lymphocytes than healthy controls. Furthermore, patients with COPD had higher percentages of sputum neutrophils (77 (29–94) versus 36 (18–60)%, p = 0.001) and eosinophils (1.2 (0–8.5) versus 0.2 (0–3.1)%, p = 0.008), BAL fluid eosinophils (0.4 (0–1.7) versus 0.2 (0–0.5)%, p = 0.03), and higher concentrations of sputum eosinophilic cationic protein (ECP) (838 (115–23 760) versus 121 (35–218) ng/ml, p<0.001). Concentrations of ECP expressed per eosinophil were not higher. Patients with COPD with high mucosal EG2+ cell numbers also had high mucosal CD4+ cell numbers. Sputum eosinophilia was associated with a decrease in FEV1/VC and BAL fluid eosinophilia with a decrease in mucosal NP57+ cells (neutrophils). CONCLUSIONS Subjects with COPD who do not currently smoke have increased numbers of inflammatory cells. Eosinophils are increased in number in the airways in COPD but do not seem to be activated. The increased eosinophil numbers are probably due to recruitment as a result of ongoing inflammation. Macrophages and lymphocytes may play a part in this inflammation.
Background: Factors contributing to either “complete” or “clinical” remission of asthma are important to know since there is no cure for the disease. Methods: A cohort of 119 allergic asthmatic ...children was examined three times with a mean follow up of 30 years. They were aged 5–14 years at visit 1 (1966–9), 21–33 years at visit 2 (1983–6), and 32–42 years at visit 3 (1995–6). Complete remission of asthma at visit 3 was defined as no asthma symptoms, no use of inhaled corticosteroids, normal lung function (FEV1 >90% predicted), and no bronchial hyperresponsiveness (PC10 >16 mg/ml). Clinical remission was defined as no asthma symptoms and no use of inhaled corticosteroids. Results: 22% of the group was in complete remission of asthma at visit 3 and a further 30% was in clinical remission (total 52%); 57% of subjects in clinical remission had bronchial hyperresponsiveness and/or a low lung function. Logistic regression analyses showed that a higher FEV1 in childhood and more improvement in FEV1 from age 5–14 to 21–33 were associated with both complete and clinical asthma remission at age 32–42. Conclusions: Complete remission of asthma was present in a small subset of asthmatics while half the subjects showed clinical remission. Both complete and clinical remission were associated with a higher lung function level in childhood and a higher subsequent increase in FEV1. These results support the view that defining remission only on the basis of symptoms and medication use will overlook subjects with subclinical active disease and possibly associated airway remodelling.
Proteases secreted by Aspergillus fumigatus induce the production of cytokines by epithelial cells, including interleukin (IL)-6 and IL-8. In the present study, we focused on the mechanism(s) by ...which A. fumigatus-deriwed proteases elicit cytokine production in epithelial cells. In the epithelial cell line A549, IL-6 and IL-8 mRNA levels were enhanced by proteases as a result of transcriptional induction of the respective genes. Transcriptional induction of both genes coincided with enhanced DNA binding of nuclear factor (NF)-κB and NF-IL6, whereas activator protein-1 was unlikely to be involved. The enhanced transcriptional activity could be inhibited by the addition of chymostatin, showing serine protease dependency. Posttranscriptional mechanisms affecting the stability of IL-6 and IL-8 mRNAs were not involved in protease-induced IL-6 and IL-8 production. These data show that after exposure to A. fumigatus-derived proteases, IL-6 and IL-8 gene expressions are up-regulated as a result of transcriptional mechanisms.
Highlights • Remitted recurrent MDD-patients show alterations in DHEAS and cortisol/DHEAS-ratio. • These alterations do not change during a recurrent depressive episode. • Morning cortisol/DHEAS ...ratio predicts recurrence over a 10-year follow-up. • This suggests altered DHEAS is part of an endophenotypic vulnerability trait in MDD. • This may be used to improve prevention of recurrence and cardiovascular comorbidity.
Highlights • Seventy unmedicated depressed patients had higher CRP and arachidonic acid than controls. • Arachidonic acid was related with CRP and amygdala reactivity. • In patients, these factors ...were longitudinally associated with antidepressant response. • These findings corroborate a role for neuroinflammation in depression and treatment response. • This may contribute to biomarker panel development to predict antidepressant success.
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