Biomarkers: past, present, and future

In recent decades biomarkers have become accepted tools in clinical practice [1]. Although there is no widely accepted definition of what constitutes a biomarker, for the context of this review we consider a biomarker to be a protein or other macromolecule that is associated with a biological process or regulatory mechanism. Hence measurement of this biomarker in blood, for example, might provide quantitative information that could be clinically helpful regarding this biological process or regulatory mechanism. In this paper we review recent advances with the use of biomarkers in three major clinical areas: diagnosis of myocardial infarction, diagnosis and management of heart failure, and diagnosis and management of inflammatory conditions in general and systemic infections in particular. Although these may look like unrelated medical challenges, recent clinical research in these areas by our groups and others has opened up opportunities and challenges that seem fundamental for biomarkers in general

Prospective Evaluation of an Algorithm for the Functional Assessment of Lung Resection Candidates

Patients with impaired pulmonary function are at increased risk for the development of postoperative complications. Recently exercise testing and predicted postoperative (ppo) function have gained increasing importance in the evaluation of lung resection candidates. We prospectively evaluated an algorithm for the preoperative functional evaluation that was developed at our institution. This algorithm incorporated the cardiac history including an electrocardiogram (ECG), and the three parameters FEV1, diffusing capacity of the lungs for carbon monoxide (DLCO), and maximal oxygen uptake ( VO2max), as well as their respective ppo values (FEV1-ppo, DLCO-ppo, and VO2max-ppo) calculated based on radionuclide perfusion scans. A consecutive group of 137 patients (mean age 62 yr; range 23 to 81; 102 males, 35 females) with clinically resectable lesions underwent assessment according to our algorithm. Five patients were deemed functionally inoperable, 132 passed the algorithm and underwent pulmonary resections with standard thoracotomy: 9 segmental or wedge resections, 85 lobectomies (inclusive 3 bilobectomies), and 38 pneumonectomies. All patients were extubated within 24 h. The mean stay in the ICU was 1.4 ( � 1.8) d, and the mean hospital stay was 14.6 ( � 5) d. Postoperative complications (within 30 d) occurred in 15 patients (11%), of whom two died (overall mortality rate 1.5%). In comparison to our previous series this meant a 50 % reduction in complications whereas the percentage of inoperable patients remained unchanged (4 % now, 5 % before). We conclude that adherence to our algorithm resulted in a very low complication rate (morbidity and mortality), and excluded more rigorous patient selection as a bias for the improved results. Wyser C

Transbronchial Needle Aspiration in Routine Fiberoptic Bronchoscopy

The objective of this study was to evaluate the yield of transbronchial needle aspiration (TBNA) in a clinical routine setting of a teaching hospital for the diagnosis and staging of bronchogenic carcinoma in comparison to the results of controlled clinical studies. We reviewed our results with Wang retractable needle catheters during a 9-month period. The needle catheters were used in 72 patients. 43 patients had a final diagnosis of bronchogenic carcinoma. Classical bronchial washes, brushings and forceps biopsies led to the diagnosis in 28 patients (65%). The addition of TBNA increased the diagnostic yield by 14% (6 patients) to 79% overall. In 32 patients staging of mediastinal lymph nodes was attempted. Positive TBNA proved inoperability in 9 patients. In 7 patients TBNA was used to investigate peripheral masses. Two patients had a malignant tumor, of which one was diagnosed by TBNA. Overall, TBNA revealed important information with clinical consequences in 16 of 72 patients (22%). There were no complications. We conclude that TBNA significantly increases the diagnostic yield of fiberoptic bronchoscopy and carries only a minimal risk. Our results, obtained in the clinical routine setting of a teaching hospital, are comparable to the reported results of controlled studies

Diagnostic value of lung auscultation in an emergency room setting

In daily routine, physicians use history, physical examination and technology-based information such as laboratory tests and imaging studies to diagnose the patients' disease. We determined the diagnostic value of lung auscultation in patients admitted to the Medical emergency room with chest symptoms.; Two-hundred-and forty-three consecutive patients (137 males), mean age 59.2 years were included. Internal Medicine registrars had to make a presumptive diagnosis, 1) after having taken the history and 2) after having auscultated the lungs. Thereafter, routine diagnostic procedures were performed. The estimated diagnosis was compared with the final diagnosis based on the written report to the Family Practitioner.; Two-hundred-eighty-seven diagnoses were made. Eighteen percent of patients suffered from left heart failure, 13% from unexplained chest pain, 10.5% from chest wall pain, and 10.5% from pneumonia. Forty-one percent of the diagnoses were already correct when based only on the patient's history. Lung auscultation improved the diagnostic yield only in 1% and worsened it in another 3%. By multiple logistic regression, normal lung auscultation (OR 0.12 [95CI% 0.053-0.29]) was the independent predictor for not having a lung or heart disease. However, elevation of B-type natiuretic peptide (BNP) (OR 1.16 per 100 pg/ml (95CI% 1.004-1.35), wheezing (OR 0.023 [0.002-0.33]) and pCO2 (OR 0.25 (0.10-0.621) were independent predictors for having a heart disease, whereas wheezing (OR 7.41 [3.26-16.83]) and CRP (OR 1.008 per 10 units [1.003-1.014]) were risk factors for having a lung disease.; In contrast to history taking, abnormal lung auscultation does not appear to contribute considerably to the final diagnosis in patients presenting with chest symptoms in an emergency room setting. However, normal lung auscultation is a valuable predictor for not having a lung or heart disease, whereas wheezing is a predictor for having a lung disease and not having a heart disease