A number of current trends will affect and probably change laboratory medicine, as we know it. Scientific and technological developments, digital health with big data and artificial intelligence, and centralization will change the interfaces among the specialties of laboratory medicine. They might even challenge the identity of some specialties. Other trends such as demographic changes, increased complexity of health care, digital health with electronic health records, and more demanding and well-informed patients will change the way laboratory medicine specialties deliver their services. This paper discusses the possible changes of laboratory medicine in Denmark a Scandinavian country where almost all hospitals are public. If Danish laboratories grasp the new possibilities instead of trying to avoid them, laboratory medicine is likely to prosper. Such a positive development will call upon good leadership and a genuine willingness among laboratory specialist to adapt to a future where their own specialty might be very different from today.

Challenging times lay ahead for laboratory medicine in Europe due to at least three factors. 1) The scientific and technological developments increase the diagnostic possibilities but at the same time they will also change the interfaces among the different specialties of laboratory medicine. 2) The demographic changes with a more elderly population increase the demands for laboratory tests. 3) The increased complexity of the health care system combined with more well-informed patients calls for more coherent clinical pathways across the different sectors, for an increased focus on patient safety, and for a stronger involvement of patients and relatives. These issues cause both threats and opportunities for laboratory medicine - and they have to be handled in a situation with limited economic growth and shortage of money. This calls for a new organization of laboratory medicine in many hospitals as well as for a more active involvement of laboratory medicine in the clinical work and in the contact with the patients. Laboratory medicine will need dedicated and skillful leadership in order to prosper and grow during these challenging changes.

Abstract Background: There is increasing interest in direct patient engagement including receiving their laboratory medicine results. We previously established an appetite for Specialists in Laboratory Medicine to support patients in understanding results. The aim of this study was to establish whether patients agreed with such an approach, determined through surveying views in eight European countries. Methods: A standardized five-question survey was administered across eight European countries to a total of 1084 individuals attending medical outpatient clinics, with 100 patients each in Poland, Serbia, Netherlands, Turkey and Czech Republic, 101 in Estonia, 116 in Denmark and 367 in Norway. The responses across countries were compared using the chi-square test (p<0.05). Results: Patients wanting their results ranged from 50% to 94% (mean 65%) of those responding positively, a mean of 72% wanted additional information with their results; direct receipt was preferred over referral to a website. Specialists in Laboratory Medicine providing such information were acceptable to a mean of 62% of those respondents wishing their results; in countries where payment was possible, there was little interest in making additional payment for such a service. Conclusions: A clear proportion of patients are interested in receiving their laboratory medicine results, the majority with explanatory notes; a role for Specialists in Laboratory Medicine is acceptable and raises the potential for direct engagement by such specialists with patients offering a new paradigm for the provision of laboratory medicine activities.

BACKGROUND:Medicine is a highly professionalized endeavour, by tradition centred on the authority of physicians. Better education and the advent of the information age cater for increased demands on society in general and on health care in particular to enable people to make informed decisions regarding themselves. Participation in medical decisions requires informed knowledge which is hard to obtain without substantial and time consuming professional help.METHODS:We performed a survey amongst the member organizations of European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) in order to investigate the recognition and preparedness of providing help to patients in interpreting their laboratory results.RESULTS:Out of 40 EFLM Member Societies, 27 sent their responses to the survey. In most cases the first line delivery of laboratory results to physicians is by computer link (63%). Patients receive their laboratory results on demand from their physician in 60% of cases. However, 34% of laboratory specialists showed a negative attitude for delivering laboratory results to patients. Yet, in 48% of countries 1-5 patients per day ask a laboratory specialist about the significance of laboratory results outside the reference range. When patients are informed about the purpose of laboratory testing, they seek information primarily from their physician, followed by the internet and the Specialist in Laboratory Medicine.CONCLUSIONS:Changing practices increasingly enabling patient access to their records are on the increase facilitated by recent innovations in information technologies. Successful transfer of some of the responsibilities of physicians, demands a mutual triangular dialogue between the patient, their physician and laboratory medicine.

Serum protein profiling by mass spectrometry is a promising method for early detection of cancer. We have implemented a combined strategy based on matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) and statistical data analysis for serum protein profiling and applied it in a well-described breast cancer case-control study. A rigorous sample collection protocol ensured high quality specimen and reduced bias from preanalytical factors. Preoperative serum samples obtained from 48 breast cancer patients and 28 controls were used to generate MALDI MS protein profiles. A total of nine mass spectrometric protein profiles were obtained for each serum sample. A total of 533 common peaks were defined and represented a 'reference protein profile'. Among these 533 common peaks, we identified 72 peaks exhibiting statistically significant intensity differences ( p < 0.01) between cases and controls. A diagnostic rule based on these 72 mass values was constructed and exhibited a cross-validated sensitivity and specificity of approximately 85% for the detection of breast cancer. With this method, it was possible to distinguish early stage cancers from controls without major loss of sensitivity and specificity. We conclude that optimized serum sample handling and mass spectrometry data acquisition strategies in combination with statistical analysis provide a viable platform for serum protein profiling in cancer diagnosis.

Protein profiling of human serum by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) is potentially a new diagnostic tool for early detection of human diseases, including cancer. Sample preparation is a key issue in MALDI MS and the analysis of complex samples such as serum requires optimized, reproducible methods for handling and deposition of protein samples. Data acquisition in MALDI MS is also a critical issue, since heterogeneity of sample deposits leads to attenuation of ion signals in MALDI MS. In order to improve the robustness and reproducibility of MALDI MS for serum protein profiling we investigated a range of sample preparation techniques and developed a statistical method based on repeated analyses for evaluation of protein-profiling performance of MALDI MS. Two different solid-phase extraction (SPE) methods were investigated, namely custom-made microcolumns and commercially available magnetic beads. Using these two methods, nineteen different sample preparation methods for serum profiling by MALDI MS were systematically tested with regard to matrix selection, stationary phase, selectivity, and reproducibility. Microcolumns were tested with regard to chromatographic properties; reversed phase (C8, C18, SDB-XC), ion-exchange (anion, weak cation, mixed-phase (SDB-RPS)) and magnetic beads were tested with regard to chromatographic properties; reversed phase (C8) or affinity chromatography (Cu-IMAC). The reproducibility of each sample preparation method was determined by enumeration and analysis of protein signals that were detected in at least six out of nine spectra obtained by three triplicate analyses of one serum sample.A candidate for best overall performance as evaluated by the number of peaks generated and the reproducibility of mass spectra was found among the tested methods. Up to 418 reproducible peaks were detected in one cancer serum sample. These protein peaks can be part of a possible diagnostic profile, suggesting that this sample preparation method and data acquisition approach is suitable for large-scale analysis of serum samples for protein profiling.

For more accurate reporting of studies of diagnostic accuracy, the STARD (Standards for Reporting of Diagnostic Accuracy) steering committee has published a checklist and a generic flow diagram [see, for an example, the checklist in Clinical Chemistry (1)]. The intention is to improve the quality and evaluation of research to the advantage of clinicians, researchers, reviewers, journals, and the public. In clinical biochemistry, many diagnostic aspects need standardization. Such standardization unfortunately does not exist for the term “fasting”, which may imply not only the duration of the fasting period but also restrictions concerning smoking, alcohol, coffee/tea consumption, and physical activity. When the patient is sent to the laboratory for fasting blood sampling, fasting instructions are given by the …

Serum profiling by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) holds promise as a clinical tool for early diagnosis of cancer and other human diseases. Sample preparation is key to achieving reproducible and well-resolved signals in MALDI-MS; a prerequisite for translation of MALDI-MS based diagnostic methods to clinical applications. We have investigated a number of MALDI matrices and several miniaturized solid-phase extraction (SPE) methods for serum protein concentration and desalting with the aim of generating reproducible, high-quality protein profiles by MALDI-MS. We developed a simple protocol for serum profiling that combines a matrix mixture of 2,5-dihydroxybenzoic acid and alpha-cyano-4-hydroxycinnamic acid with miniaturized SPE and MALDI-MS. Functionalized membrane discs with hydrophobic, ion-exchange or chelating properties allowed reproducible MALDI mass spectra (m/z 1000-12,000) to be obtained from serum. In a proof-of-principle application, SPE with chelating material and MALDI-MS identified protein peaks in serum that had been previously reported for distinguishing a person diagnosed with breast cancer from a control. These preliminary results indicate that this simple SPE/MALDI-MS method for serum profiling provides a versatile and scalable platform for clinical proteomics.

Both glomerular and tubular markers have been used to follow diabetic nephropathy. However, neither albumin nor proximal tubular markers have proven useful in prepubertal diabetes. Hence we studied two markers derived from the distal tubular cells, Tamm-Horsfall protein (THP) and epidermal growth factor (EGF). The urinary excretion of THP and EGF was examined in samples obtained during the first 20 days and 1 year after diagnosis of diabetes in children aged 4–15 years. Fourteen children without and 18 with ketonuria were examined, and 17 age-matched healthy children participated as controls. The excretion rate of EGF was increased at diagnosis, while that of THP was not. After 20 days of treatment the excretion of EGF had normalized, while the excretion of THP was decreased. Similar results were obtained after 1 year. In conclusion, in spite of good metabolic control a reduced excretion of THP persisted for at least 1 year after the diagnosis of diabetes. Whether the finding of reduced excretion of THP has any biological significance awaits further study.

The purpose of this study was to evaluate the in vitro synergism between piperacillin and netilmicin against microorganisms isolated from Danish patients with septicemia and to examine the influence of inactivation of piperacillin among these bacteria on the synergy results. A total of 132 stains was examined: Escherichia coli 20, indole-positive Proteus 17, Klebsiella pneumoniae 18, Enterobacter cloacae 20, Pseudomonas aeruginosa 20, Staphylococcus aureus 20, and coagulase-negative staphylococci 17. Synergy testing was performed by checkerboard titration in microtiter trays. The ability of the strains to inactivate piperacillin was examined by the clover-leaf test. Synergism was found for 52% of the strains and partial synergism for 32%. Antagonism was not found. Of the piperacillin-resistant strains synergism could be demonstrated in 80% compared with 33% of the piperacillin-susceptible strains (p less than 0.001). No significant correlation was seen between the results of the synergy test and the results of the susceptibility test to netilmicin. The frequency of piperacillin inactivation according to the clover-leaf test was significantly higher among the strains with synergism than among all the others (p less than 0.02). The combination of piperacillin and netilmicin gave good results concerning the in vitro synergism. This synergism was probably sometimes caused by netilmicin disturbing the bacterial production of piperacillin-inactivating proteins.

The suitability of a very sensitive modification of the clover-leaf test as a test for inactivation of beta-lactam antibiotics by gram-negative rods was examined. 143 Enterobacteriaceae and 9 strains of Pseudomonas aeruginosa were examined by the clover-leaf test and an antibiotic susceptibility test towards 12 beta-lactam antibiotics. The beta-lactamase activity of the strains was also examined by a sensitive modification of the chromogenic cephalosporin test. The strains of P. aeruginosa could not be clover-leaf tested as they inhibited the indicator strains. All the Enterobacteriaceae which had beta-lactamase activity according to the chromogenic test inactivated at least 1 of the antibiotics in the clover-leaf test. None of the Enterobacteriaceae without beta-lactamase activity inactivated any of the antibiotics. On the whole the results of the clover-leaf test and the results of the susceptibility test correlated well. But many Enterobacteriaceae were susceptible to an antibiotic in the susceptibility test even though they inactivated it according to the clover-leaf test and some Enterobacteriaceae were resistant to an antibiotic but did not inactivate it. Among the Enterobacteriaceae which had beta-lactamase activity according to the chromogenic cephalosporin test and which were intermediately susceptible to an antibiotic in the susceptibility test, many did not inactivate this antibiotic according to the clover-leaf test. If an infection with Enterobacteriaceae has to be treated by a beta-lactam antibiotic to which the strain is only intermediately susceptible, it might be advantageous to use an antibiotic which is not inactivated by the strain according to the clover-leaf test, but this lacks clinical confirmation.