Incorporation of age into patient early warning scores significantly improves mortality prediction.

BACKGROUND: Age is a critical factor for the assessment of patients attended by emergency medical services (EMSs). However, how age modifies early warning scores' (EWSs) predictive ability should be unveiled. AIM: To determine how age influences the performance of EWS [National Early Warning Score 2 (NEWS2), VitalPAC-Early Warning Score (ViEWS), Rapid Acute Physiology Score (RAPS) and modified Rapid Emergency Medicine Score (mREMS)] to predict 2-day mortality. The secondary objective was to determine the performance of EWSs at different age ranges. DESIGN: A prospective, observational study performed between November 2019 and July 2023. METHODS: A multicenter, ambulance-based study, considering 38 basic life support units and six advanced life support units referring to four tertiary care hospitals. Eligible patients were adults recruited from among all phone requests for emergency assistance who were later evacuated to emergency departments. The primary outcome was 2-day in-hospital mortality (includes all-cause mortality). The main measures were demographical and vital signs needed for EWS calculation. RESULTS AND DISCUSSION: A total of 8028 participants fulfilled the inclusion criteria, with 7654 survivors and 374 non-survivors. Among age ranges, the 2-day mortality was 2.8% for the ≤44 years, 3.3% for the 45-64 years, 4.1% for the 65-74 years and 6.7% for the ≥75-year age group. The inclusion of age significantly improved the Area Under the Curve (AUC) in all the scores (P = 0.006 for non-age-adjusted mREMS, P = 0.001 for NEWS2, P = 0.002 for ViEWS, P = 0.028 for RAPS, all compared with their counterparts with age). CONCLUSION: Our results demonstrated that the incorporation of age into the EWS improved the performance of the scores. These results will allow the EMS to improve patient management and resource optimization by including an easy-to-obtain variable.

[System and skill utilization in an Austrian emergency physician system: retrospective study]. / System- und Fertigkeitseinsatz in einem österreichischen Notarztsystem: retrospektive Studie.

BACKGROUND: The continuous rise in calls for emergency physicians and the low proportion of indicated missions has led to a loss of job attractiveness, which in turn renders services in some areas unable to sufficiently staff units. This retrospective analysis evaluated the frequency of emergency and general medical interventions in a ground-based emergency physician response system. METHODS: A retrospective analysis of anonymized data from the electronic documentation system of the emergency physician response unit at the Medical University of Graz was carried out. Calls answered by emergency physicians between 2010 and 2018 were extracted, measures carried out were evaluated and categorized into three groups: specific emergency interventions (category I), general medical interventions (category II) and no medical activity (category III). The frequency of occurrence of these categories was compared and incidences of individual measures per 100,000 inhabitants were calculated. RESULTS: A total of 15,409 primary responses and 322 secondary transports were extracted and analyzed. The annual rate of system activation rose almost continuously from 1442 calls in 2010 to 2301 calls in 2018. The 3687 (23.4%) cancellations resulted in 12,044 patient contacts. Of these, 2842 (18%) calls were coded as category I, 7372 (47%) as category II and 5518 (35%) as category III. The frequency of specific emergency measures and general medical interventions was estimated at 157/100,000 and 409/100,000 inhabitants, respectively. CONCLUSIONS: No specific emergency physician interventions were required in the majority of call-outs. The current model of preclinical care does not appear to be patient-oriented and efficient. Furthermore, the low proportion of critically ill and injured patients already leads to a reduction in attractiveness for emergency physicians and may introduce the threat of quality issues due to insufficient routine experience and lack of training.

[Magnetic resonance imaging of the lungs in cystic fibrosis]. / Magnetresonanztomographie der Lunge bei Mukoviszidose.

CLINICAL ISSUE: Disease severity and mortality in patients with cystic fibrosis (CF) is mainly determined by (progressive) pulmonary lung disease. Early diagnosis and therapy are important and of prognostic value to conserve lung function. STANDARD RADIOLOGICAL METHODS: Primary imaging techniques for lung imaging are x­ray and computed tomography (CT) to monitor disease severity and regional distribution. METHODICAL INNOVATIONS: Radiation-free imaging techniques such as magnetic resonance imaging (MRI) have gained interest over the last decade in order to prevent radiation damage. PERFORMANCE: The main findings of CF lung disease are airway wall thickening, bronchiectasis, and mucus plugging, which are found in up to 60% of preschool age children. Pleural abnormalities and consolidations are often associated with pulmonary exacerbation. Young CF patients often show a mosaic pattern as functional changes and also perfusion defects can be seen from birth in 50% of CF patients by contrast-enhanced perfusion imaging, and in up to 90% of adult patients, with varying degrees of severity. Dilated bronchial arteries indicate an increased risk for hemoptysis. ACHIEVEMENTS: Proton MRI is the sole imaging technique that can show structural and functional lung changes in one examination. Structured assessment using a scoring system helps to systematically grade the extent and severity of all CF-associated changes. CONCLUSIONS: Lung MRI for cystic fibrosis has been recently established as a clinical standard examination and is routinely performed at experienced centers. More recently, it has also been used as an endpoint within the framework of clinical studies.

[Cystic fibrosis and computed tomography of the lungs]. / Computertomographie der Lunge bei Mukoviszidose.

With its high detail of morphological changes in lung parenchyma and airways as well as the possibilities for three-dimensional reconstruction, computed tomography (CT) represents a solid tool for the diagnosis and follow-up in patients suffering from cystic fibrosis (CF). Guidelines for standardized CT image acquisition in CF patients are still missing. In the mostly younger CF patients, an important issue is the well-considered use of radiation in CT imaging. The use of intravenous contrast agent is mainly restricted to acute emergency diagnostics. Typical morphological findings in CF lung disease are bronchiectasis, mucus plugging, or signs of decreased ventilation (air trapping) which can be detected with CT even in early stages. Various scoring systems that have become established over time are used to grade disease severity and for structured follow-up, e.g., in clinical research studies. With the technical development of CT, a number of postprocessing software tools were developed to help clinical reporting and overcome interreader differences for a standardized quantification. As an imaging modality free of ionizing radiation, magnetic resonance imaging (MRI) is becoming increasingly important in the diagnosis and follow-up of CF patients and is already frequently a substitute for CT for long-term follow-up at numerous specialized centers.

[Proximal Row Carpectomy - Five-Year Results]. / Proximální karpektomie ­ petileté výsledky.

PURPOSE OF THE STUDY This study aims to evaluate the results of patients treated by proximal row carpectomy at a follow-up of at least 5 years after the surgery. MATERIAL AND METHODS A total of 25 patients were treated by proximal row carpectomy for degenerative changes of the wrist as a consequence of the previous trauma or avascular necrosis of the lunate bone, of whom 21 patients underwent a follow-up examination at least 5 years postoperatively. Proximal row carpectomy was indicated in 15 patients for SLAC wrist, in 4 patients for avascular necrosis of the lunate bone, in 1 patient for SNAC wrist, and in 1 patient for inveterate dislocation of the wrist. The follow-up clinical and radiological examinations were performed at least 5 years after the surgery. The range of wrist motion, grip strength, presence of pain at rest or pain under loads, total clinical score according to the Green and O'Brien scoring system, patient satisfaction with the outcome of surgery were assessed. By fluoroscopy the range of wrist motion, degenerative changes of the radiocapitate joint, and translation of the capitate bone with respect to the distal radius were evaluated. RESULTS Postoperative improvements in the range of motion and grip strength were confirmed. Also, the pain relief at rest and under loads was achieved. Five years after the surgery, most of the patients (85.6%) reported an overall improvement. The total clinical score according to the Green and O'Brien scoring system improved from 35.8 preoperatively to 63.1 postoperatively. DISCUSSION The advantage of this procedure is a low percentage of complications, relative technical simplicity, maintenance of functional motion of the wrist, satisfactory grip strength, and pain relief. There are no complications related to the implant, no risk of a non-union. CONCLUSIONS As shown by our results obtained 5 years after the surgery as well as the published data, in the indicated cases the proximal row carpectomy is an appropriate surgical technique to treat the degenerative changes of the wrist. In most of the patients, favourable functional results and pain relief can be expected. Key words:proximal row carpectomy, SLAC wrist, SNAC wrist, avascular necrosis of the lunate bone, dislocation of the wrist.

Imaging of Cystic Fibrosis Lung Disease and Clinical Interpretation.

UNLABELLED: Progressive lung disease in cystic fibrosis (CF) is the life-limiting factor of this autosomal recessive genetic disorder. Increasing implementation of CF newborn screening allows for a diagnosis even in pre-symptomatic stages. Improvements in therapy have led to a significant improvement in survival, the majority now being of adult age. Imaging provides detailed information on the regional distribution of CF lung disease, hence longitudinal imaging is recommended for disease monitoring in the clinical routine. Chest X-ray (CXR), computed tomography (CT) and magnetic resonance imaging (MRI) are now available as routine modalities, each with individual strengths and drawbacks, which need to be considered when choosing the optimal modality adapted to the clinical situation of the patient. CT stands out with the highest morphological detail and has often been a substitute for CXR for regular severity monitoring at specialized centers. Multidetector CT data can be post-processed with dedicated software for a detailed measurement of airway dimensions and bronchiectasis and potentially a more objective and precise grading of disease severity. However, changing to CT was inseparably accompanied by an increase in radiation exposure of CF patients, a young population with high sensitivity to ionizing radiation and lifetime accumulation of dose. MRI as a cross-sectional imaging modality free of ionizing radiation can depict morphological hallmarks of CF lung disease at lower spatial resolution but excels with comprehensive functional lung imaging, with time-resolved perfusion imaging currently being most valuable. KEY POINTS: • Hallmarks are bronchiectasis, mucus plugging, air trapping, perfusion abnormalities, and emphysema.• Imaging is more sensitive to disease progression than lung function testing.• CT provides the highest morphological detail but is associated with radiation exposure.• MRI shows comparable sensitivity for morphology but excels with additional functional information.• MRI sensitively depicts reversible abnormalities such as mucus plugging and perfusion abnormalities. Citation Format: • Wielpütz MO, Eichinger M, Biederer J et al. Imaging of Cystic Fibrosis Lung Disease and Clinical Interpretation. Fortschr Röntgenstr 2016; 188: 834 - 845.

Randomized Study on Early Detection of Lung Cancer with MSCT in Germany: Results of the First 3 Years of Follow-up After Randomization.

INTRODUCTION: The German Lung Cancer Screening Intervention Trial (LUSI) is one of the European randomized trials investigating the efficacy of low-dose multislice computed tomography (MSCT) as a screening tool for lung cancer. In the evaluation of the first (prevalence) screening round, we observed exceptionally high early recall rates, which made the routine application of MSCT screening questionable. Because screening may behave differently in subsequent (incidence) screening rounds, we analyzed (a) basic characteristics for the annual rounds 2 to 4, which have now also been completed, and (b) the first 3 years with complete follow-up since time of randomization. METHODS: Data material was the data record of LUSI after the fourth screening round and the 3-year follow-up had been completed. Basic characteristics of screening, e.g., early recall rate, detection rate, and interval cancers as well of proportion of advanced cancers, were descriptively evaluated and, if informative, group differences were tested for statistical significance. RESULTS: Early recall rates were significantly lower in the subsequent screening rounds than in the first one if the MSCT information from the previous screening rounds was available. Detection and biopsy rates were approximately 1% or lower, ratio of benign:malignant biopsies: 1:1.6 to 1:3. CONCLUSION: Our recent data may not only settle one concern regarding high recall rates in routine MSCT screening but also indicate that screening must be strictly organized to be effective. Performance indicators are similar to those in mammography screening. Nevertheless, possible consequences for the participants (diagnostic workup of suspicious findings, biopsies) are more invasive than in mammography screening.

Inter-observer reproducibility of semi-automatic tumor diameter measurement and volumetric analysis in patients with lung cancer.

OBJECTIVES: Therapy monitoring in oncologic patient requires precise measurement methods. In order to improve the precision of measurements, we used a semi-automated generic segmentation algorithm to measure the size of large lung cancer tumors. The reproducibility of computer-assisted measurements were assessed and compared with manual measurements. METHODS: CT scans of 24 consecutive lung cancer patients who were referred to our hospital over a period of 6 months were analyzed. The tumor sizes were measured manually by 3 independent radiologists, according to World Health Organization (WHO) and the Revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. At least 10 months later, measurements were repeated semi-automatically on the same scans by the same radiologists. The inter-observer reproducibility of all measurements was assessed and compared between manual and semi-automated measurements. RESULTS: Manual measurements of the tumor longest diameter were significantly (p < 0.05) smaller compared with the semi-automated measurements. The intra-rater correlations coefficients were significantly higher for measurements of longest diameter (intra-class correlation coefficients: 0.998 vs. 0.986; p < 0.001) and area (0.995 vs. 0.988; p = 0.032) using semi-automated compared with manual method. The variation coefficient for manual measurement of the tumor area (WHO guideline, 15.7% vs. 7.3%) and the longest diameter (RECIST guideline, 7.7% vs. 2.7%) was 2-3 times that of semi-automated measurement. CONCLUSIONS: By using computer-assisted size assessment in primary lung tumor, interobserver-variability can be reduced to about half to one-third compared to standard manual measurements. This indicates a high potential value for therapy monitoring in lung cancer patients.

Randomized study on early detection of lung cancer with MSCT in Germany: study design and results of the first screening round.

PURPOSE: Low-dose multislice-CT (MSCT) detects many early-stage lung cancers with good prognosis, but whether it decreases lung cancer mortality and at which costs is yet insufficiently explored. Scope of the present study is to examine within a common European effort whether MSCT screening is capable to reduce the lung cancer mortality by at least 20 % and at which amount of undesired side effects this could be achieved. METHODS: Overall 4,052 heavy smoking men and women were recruited by a population-based approach and randomized into a screening arm with five annual MSCT screens and an initial quit-smoking counseling, and a control arm with initial quit-smoking counseling and five annual questionnaire inquiries. RESULTS: In the first screening round, 2,029 participants received a MSCT providing 1,488 negative and 540 suspicious screens with early recalls (early recall rate 26.6 %) leading to 31 biopsies (biopsy rate 1.5 %) and 22 confirmed lung cancers (detection rate 1.1 %). Among the lung cancers, 15 were adenocarcinomas, 3 squamous cell carcinomas, one small-cell lung cancer, and 3 others, whereby 18 were in clinical stage I, one in stage II, and 3 in stage III. One interval cancer occurred. CONCLUSIONS: The indicated performance indicators fit into the range observed in comparable trials. The study continues finalizing the second screening round and for the first participants even the last screening round. The unresolved issue of the precise amount of side effects and the high early recall rate precludes currently the recommendation of MSCT as screening tool for lung cancer.

In vivo monitoring of cystic fibrosis-like lung disease in mice by volumetric computed tomography.

The onset and spontaneous development of cystic fibrosis (CF) lung disease remain poorly understood. In the present study, we used volumetric computed tomography (VCT) as a new method for longitudinal in vivo monitoring of early lesions and disease progression in CF-like lung disease in ß-epithelial Na(+) channel (ENaC)-transgenic (TG) mice. Using a VCT scanner prototype (80 kV, 50 mA·s, scan time 19 s and spatial resolution 200 µm), ßENaC-TG mice and wild-type (WT) littermates were examined longitudinally at 10 time-points from neonatal to adult ages, and VCT images were assessed by qualitative and quantitative morphological parameters. We demonstrate that VCT detected early-onset airway mucus obstruction, diffuse infiltrates, atelectasis and air trapping as characteristic abnormalities in ßENaC-TG mice. Furthermore, we show that early tracheal mucus obstruction predicted mortality in ßENaC-TG mice and that the density of lung parenchyma was significantly reduced at all time-points in ßENaC-TG compared with WT mice (median ± sem -558 ± 8 HU in WT versus -686 ± 16 HU in ßENaC-TG at 6 weeks of age; p < 0.005). Our study demonstrates that VCT is a sensitive, noninvasive technique for early detection and longitudinal monitoring of morphological abnormalities of CF-like lung disease in mice, and may thus provide a useful tool for pre-clinical in vivo evaluation of novel treatment strategies for CF.

[Magnetic resonance imaging of respiratory movement and lung function]. / Magnetresonanztomographie der Atembewegung und Lungenfunktion.

Lung function measurements are the domain of spirometry or plethysmography. These methods have proven their value in clinical practice, nevertheless, being global measurements the functional indices only describe the sum of all functional units of the lung. Impairment of only a single component of the respiratory pump or of a small part of lung parenchyma can be compensated by unaffected lung tissue. Dynamic imaging can help to detect such local changes and lead to earlier adapted therapy. Magnetic resonance imaging (MRI) seems to be perfect for this application as it is not hampered by image distortion as is projection radiography and it does not expose the patient to potentially harmful radiation like computed tomography. Unfortunately, lung parenchyma is not easy to image using MRI due to its low signal intensity. For this reason first applications of MRI in lung function measurements concentrated on the movement of the thoracic wall and the diaphragm. Recent technical advances in MRI however might allow measurements of regional dynamics of the lungs.

MRI of respiratory dynamics with 2D steady-state free-precession and 2D gradient echo sequences at 1.5 and 3 Tesla: an observer preference study.

To compare the image quality of dynamic lung MRI with variations of steady-state free-precession (SSFP) and gradient echo (GRE) cine techniques at 1.5 T and 3 T. Ventilated porcine lungs with simulated lesions inside a chest phantom and four healthy human subjects were assessed with SSFP (TR/TE=2.9/1.22 ms; 3 ima/s) and GRE sequences (TR/TE=2.34/0.96 ms; 8 ima/s) as baseline at 1.5 and 3 T. Modified SSFPs were performed with nine to ten images/s (parallel imaging factors 2 and 3). Image quality for representative structures and artifacts was ranked by three observers independently. At 1.5 T, standard SSFP achieved the best image quality with superior spatial resolution and signal, but equal temporal resolution to GRE. SSFP with improved temporal resolution was ranked second best. Further acceleration (PI factor 3) was of no benefit, but increased artifacts. At 3 T, GRE outranged SSFP imaging with high lesion signal intensity, while artifacts on SSFP images increased visibly. At 1.5 T, a modified SSFP with moderate parallel imaging (PI factor 2) was considered the best compromise of temporal and spatial resolution. At 3 T, GRE sequences remain the best choice for dynamic lung MRI.

Lung hyperinflation: foe or friend?

Breath-hold divers employ glossopharyngeal insufflation (GI) in order to prevent the lungs from compressing at great depth and to increase intrapulmonary oxygen stores, thus increasing breath-hold time. The presented case study shows the physiological data and dynamic magnetic resonance imaging (dMRI) findings of acute hyperinflation, deliberately induced by GI, in a breath-hold diver and discusses the current state of knowledge regarding the associated hazards of this unique competitive sport. Static and dynamic lung volumes and expiratory flows were within the normal range, with vital capacity and peak expiratory flow being higher than the predicted values. Airway resistance and diffusing capacity of the lung for carbon monoxide were normal. Static compliance was normal and increased five-fold with hyperinflation. dMRI revealed a preserved shape of the thorax and diaphragm with hyperinflation. A herniation of the lung beneath the sternum and enlargement of the costodiaphragmatic angle were additional findings during the GI manoeuvre. After expiration, complete resolution to baseline was demonstrated. Hyperinflation can be physiological and even protective under abnormal physical conditions in the sense of acute adaptation to deep breath-hold diving. Dynamic magnetic resonance imaging is adequate for visualisation of the sequence of the glossopharyngeal insufflation manoeuvre and the complete reversibility of deliberate hyperinflation.

Semiautomatic assessment of respiratory motion in dynamic MRI--comparison with simultaneously acquired spirometry.

PURPOSE: Supplementing global spirometry with regional information could allow for earlier and more specific diagnosis of lung disease. Dynamic magnetic resonance imaging (dMRI) makes it possible to derive functional parameters from the visualization of the pulmonary motion of single lungs. The aim of this study was to compare high temporal resolution measurements of left and right thoracic diameters to simultaneously acquired spirometry. MATERIALS AND METHODS: 10 healthy volunteers underwent 2-dimensional dMRI of both lungs at 1.5 T. Spirometry was performed simultaneously with an MRI-compatible spirometer. Thoracic diameters were measured semiautomatically and compared to simultaneously measured spirometric volumes. A dMRI surrogate for the Tiffeneau Index was compared to the spirometric Tiffeneau. RESULTS: The volume-time and flow-volume curves from dMRI were very similar to the spirometric curves. The semiautomatically measured diameters correlated well with the spirometric volumes (r > = 0.8, p < 10 - 15). Agreement between the methods at full temporal resolution was not as convincing (width of 95 % limits of agreement interval up to 56 %). Good agreement was found between the Tiffenau surrogate and spirometry (width of 95 % limits of agreement interval of 14.5 %). CONCLUSION: DMRI with semiautomatic measurement of thoracic diameters makes measurement of realistic volume-time and flow-volume curves from single lungs possible. The derived single lung Tiffeneau Index shows good agreement to spirometry and could be valuable to supplement global spirometric measurements with functional data from single lungs.

MR imaging of the chest: a practical approach at 1.5T.

Magnetic resonance imaging (MRI) is capable of imaging infiltrative lung diseases as well as solid lung pathologies with high sensitivity. The broad use of lung MRI was limited by the long study time as well as its sensitivity to motion and susceptibility artifacts. These disadvantages were overcome by the utilisation of new techniques such as parallel imaging. This article aims to propose a standard MR imaging protocol at 1.5T and presents a spectrum of indications. The standard protocol comprises non-contrast-enhanced sequences. Following a GRE localizer (2D-FLASH), a coronal T2w single-shot half-Fourier TSE (HASTE) sequence with a high sensitivity for infiltrates and a transversal T1w 3D-GRE (VIBE) sequence with a high sensitivity for small lesions are acquired in a single breath hold. Afterwards, a coronal steady-state free precession sequence (TrueFISP) in free breathing is obtained. This sequence has a high sensitivity for central pulmonary embolism. Distinct cardiac dysfunctions as well as an impairment of the breathing mechanism are visible. The last step of the basic protocol is a transversal T2w-STIR (T2-TIRM) in a multi-breath holds technique to visualize enlarged lymph nodes as well as skeletal lesions. The in-room time is approximately 15min. The extended protocol comprises contrast-enhanced sequences (3D-GRE sequence (VIBE) after contrast media; about five additional minutes). Indications are tumorous lesions, unclear (malignant) pleural effusions and inflammatory diseases (vaskulitis). A perfusion analysis can be achieved using a 3D-GRE in shared echo-technique (TREAT) with a high temporal resolution. This protocol can be completed using a MR-angiography (3D-FLASH) with high spatial resolution. The in-room time for the complete protocol is approximately 30min.

Magnetic resonance-compatible-spirometry: principle, technical evaluation and application.

The aim of this study was to assess the feasibility and accuracy of a novel magnetic resonance-compatible (MRc)-spirometer. The influence of body posture, magnetic resonance (MR)-setting and image acquisition on lung function was evaluated. Dynamic MR imaging (dMRI) was compared with simultaneously measured lung function. The development of the MRc-spirometer was based on a commercial spirometer and evaluated by flow-generator measurements and forced expiratory manoeuvres in 34 healthy nonsmokers (17 females and 17 males, mean age 32.9 yrs). Mean differences between forced expiratory volume in one second (FEV(1)) and forced vital capacity (FVC) were calculated and a sample paired t-test and Bland-Altman plots were generated. A total of 11 subjects underwent different subsequent MRc-spirometric measurements to assess the influence of the components of the MR system on lung function. The mean (95% confidence interval) difference of FEV(1) and FVC between the two systems was 0.004 (-0.04-0.04) L and 0.018 (-0.05-0.09) L, respectively. In the subgroup analysis, an influence of the MR-system on FEV(1) was found. FEV(1) correlated well with the dMRI measurement of the apico-diaphragmatic distance-change after the first second of forced expiration (r = 0.72). In conclusion, magnetic resonance-compatible-spirometry is feasible, reliable and safe. The magnetic resonance-setting only has a small influence on simultaneously measured forced expiratory volume in one second. Dynamic magnetic resonance imaging measurements correlate well with simultaneously acquired lung function parameters.

[MRI in mucoviscidosis (cystic fibrosis)]. / MRT bei Mukoviszidose.

Cystic fibrosis (CF) is a multi-systemic disease with major impact on the lungs. Pulmonary manifestation is crucial for the prognosis and life expectancy of patients. Imaging modalities and lung function tests reflect the pulmonary status in these patients. The standard imaging modality for diagnosis and follow-up of pulmonary changes is chest x-ray. The gold standard for the detection of parenchymal lung changes remains high resolution computed tomography (HRCT), but this is not used routinely for CF-patients due to radiation exposure. Magnetic resonance imaging (MRI) used to be of no importance in monitoring cystic fibrosis lung disease, as shown in studies from the 1980s and early 1990 s. The continuing improvement of MRI techniques, however, has allowed for an adequate application of this non-radiation method in diagnosing the major pulmonary findings in CF, in addition to the assessment of lung function.

Influence of the heme pocket conformation on the structure and vibrations of the Fe-CO bond in myoglobin: a QM/MM density functional study.

The influence of the distal pocket conformation on the structure and vibrations of the heme-CO bond in carbonmonoxy myoglobin (MbCO) is investigated by means of hybrid QM/MM calculations based on density functional theory combined with a classical force field. It is shown that the heme-CO structure (QM treated) is quite rigid and not influenced by the distal pocket conformation (MM treated). This excludes any relation between FeCO distortions and the different CO absorptions observed in the infrared spectra of MbCO (A states). In contrast, both the CO stretch frequency and the strength of the CO...His64 interaction are very dependent on the orientation and tautomerization state of His64. Our calculations indicate that the CO...N(epsilon) type of approach does not contribute to the A states, whereas the CO...H-N(epsilon) interaction is the origin of the A(1) and A(3) states, the His64 residue being protonated at N(epsilon). The strength of the CO...His64 interaction is quantified, in comparison with the analogous O(2)...His64 interaction and with the observed changes in the CO stretch frequency. Additional aspects of the CO...His64 interaction and its biological implications are discussed.