[Memorandum 'Development of health services research in Bavaria from the perspective of the Bavarian State Working Group 'Health Services Research (LAGeV)': status quo - potential - strategies']. / Memorandum "Weiterentwicklung der Gesundheitsversorgungsforschung in Bayern aus Sicht der Landesarbeitsgemeinschaft Gesundheitsversorgungsforschung: Status quo - Entwicklungspotenziale - Strategien".

The aim of the memorandum on the development of health services research (HSR) in Bavaria is to operationalise the global objectives of the State Working Group "Health Services Research" (LAGeV) and to collectively define future topics, specific implementation steps, methods as well as ways of working for the future course of the LAGeV. The LAGeV is an expert committee that integrates and links the competencies of different actors from science, politics and health care regarding HSR and facilitates their cooperation. The memorandum is based on an explorative survey among the LAGeV members, which identified the status quo of health services research in Bavaria, potential for development, important constraints, promoting factors, specific recommendations as well as future topics for the further development of HSR in Bavaria. From the perspective of the LAGeV members, the 12 most important future topics are: 1) Interface and networking research, 2) Innovative health care concepts, 3) Health care for multimorbid patients, 4)Health care for chronically ill patients, 5) Evaluation of innovations, processes and technologies, 6) Patient orientation and user focus, 7) Social and regional inequalities in health care, 8) Health care for mentally ill patients, 9) Indicators of health care quality, 10) Regional needs planning, 11) Practical effectiveness of HSR and 12) Scientific use of routine data. Potential for development of HSR in Bavaria lies a) in the promotion of networking and sustainable structures, b) the establishment of an HSR information platform that bundles information and results in regard to current topics and aims to facilitate cooperation as well as c) in the initiation of measures and projects. The latter ought to pinpoint health care challenges and make recommendations regarding the improvement of health care and its quality. The cooperation and networking structures that were established with the LAGeV should be continuously expanded and be used to work on priority topics in order to achieve the global objectives of the LAGeV.

[Coxarthrosis--an update]. / Koxarthrose--ein Update.

Degenerative osteoarthritis of the hip joint (coxarthrosis) is the most common disease of the hip joint in adults. The diagnosis is based on a combination of radiographic findings and characteristic clinical symptoms. The lack of a radiographic consensus definition has seemingly resulted in a variation of the published incidences and prevalence of degenerative osteoarthritis of the hip joint. The chronological sequence of degeneration includes the following basic symptoms on conventional radiographs and CT: joint space narrowing, development of osteophytes, subchondral demineralisation/sclerosis and cyst formation, as well as loose bodies, joint malalignment and deformity. MR imaging allows additional visualization of early symptoms and/or activity signs such as cartilage edema, cartilage tears and defects, subchondral bone marrow edema, synovial edema and thickening, joint effusion and muscle atrophy.The scientific dispute concerns the significance of (minimal) joint malalignment (e.g. impingement, dysplasia etc.) and forms of malpositioning which as possible prearthrosis have a high probability of leading to degenerative osteoarthritis. Moreover, without any question, the preservation of joint containment and gender differences are important additional basic diagnostic principles, which have gained great interest in recent years.In research different MR procedures such as Na and H spectroscopy, T2*-mapping etc. with ultrahigh field MR allow cartilage metabolism and its changes in early degenerative osteoarthritis ("biochemical imaging") to be studied. There is no doubt that even in a few years new profound knowledge is to be expected in this field.

Peripheral large or giant fusiform middle cerebral artery aneurysms: report of our experience and review of literature.

Peripheral large and giant middle cerebral artery (MCA) aneurysms are rare and difficult to treat. We report our and others' experience with different possible modalities used to treat such lesions. Three patients were treated differently at our institution. One harboured a giant fusiform aneurysm on a peripheral branch of the superior trunk of the left MCA, and was treated by extracranial-intracranial (EC-IC) bypass and trapping of the aneurysm. The second patient was harbouring a large fusiform aneurysm on a peripheral branch of the inferior trunk of the right MCA, which was treated by trapping and excision without the need of an EC-IC bypass as assessed pre- and intraoperatively, while the last case was harbouring a giant fusiform aneurysm at the junction of M2-M3 and was treated by EC-IC bypass and end-to-end anastomosis after resection of the aneurysm. The aneurysms proved to be neither mycotic nor dissecting. The patients were clinically intact during their perioperative course without any postoperative complications and required no further treatment. Follow-up angiography demonstrated a functioning EC-IC bypass. Based on the surgical experience in these 3 cases and a review of the reported literature, the authors propose that when considering surgical treatment for such rarely encountered aneurysms, careful pre- and intraoperative evaluation including aneurysm trapping with or without EC-IC bypass when possible should be performed to obtain a satisfactory result without complication.

Hemorrhagic cerebral dissecting aneurysms: surgical treatments and results.

INTRODUCTION: Cerebral dissecting aneurysms are an increasingly recognized etiology of subarachnoid hemorrhage SAH and cerebral stroke. Hemorrhagic dissecting aneurysms of the anterior circulation have been considered to be somewhat different to those of the posterior circulation not only in terms of their pathophysiology, but also in terms of their management. Herewith our series of hemorrhagic dissecting aneurysms of the internal carotid artery ICA, vertebral artery VA, basilar artery BA and some of those of distal cerebral arteries is presented and compared to the series reported in the literature. Therapeutic consideration in the light of our experiences emphasizing the significance of aneurysm entrapment in combination with bypass surgery is presented. MATERIAL AND METHODS: During the last 13 years over 1000 patients with cerebral aneurysms were treated surgically in our department. Hemorrhagic dissecting aneurysms were diagnosed in 26 patients. Diagnosis was based on neuroradiological findings as well as intraoperative findings. All patients underwent surgical intervention. Clinical findings of these patients were analysed retrospectively. Follow-up outcomes were evaluated according to the Glasgow Outcome Scale GOS at 3 months after treatments. RESULTS: Location of 26 dissecting aneurysms was: ICA 11 cases (42%), VA 9 cases (35%), BA 3 cases, MCA 2 cases and PCA (P1 segment) one case. Primary surgical treatments were performed on day 3.7 of SAH on average. Clinical manifestation of dissecting aneurysms of the ICA and their outcome was more severe compared with those of the VA (p < 0.01): WNFS grade 3.1 vs 2.4 and GOS score 3.4 vs 4.3. As a conventional neck clipping procedure was problematic or impossible (aneurysm recurrence after clipping, premature rupture at the time of exposure or clipping), entrapment (or proximal ligation) plus EC-IC bypass procedure was the most frequent final definitive method of surgical treatment (9/26 35%: ICA 6/11, VA 1/9 and MCA 2/2) followed by proximal ligation or trapping only 7/26, neck clipping 7/26 and coating 4/26. CONCLUSIONS: Hemorrhagic dissecting aneurysms still remain problematic in their diagnosis and treatment. One has to be aware of the diagnostic possibility of dissecting aneurysms as an etiology of SAH. Neurosurgeons have to be prepared to be able to manage complex surgical situations also by the use of EC-IC bypass, as its combination with entrapment procedure can be the final treatment of choice. Less invasive endovascular technique is in evolution but its availability and superiority are still to be settled.

Emergency extra-intracranial bypass surgery in the treatment of cerebral aneurysms.

The need of an emergency bypass in hazardous situations during treatment of intracranial aneurysms has rarely been addressed in the literature. We report our 10 year experience with emergency bypass for aneurysm treatment. We retrospectively analyzed the data of patients who underwent emergency bypass surgery for the treatment of an intracranial aneurysm and compared the results with patients treated with bypass as a planned procedure during the same time period. Three groups were formed: group I, emergency bypass during clipping procedure; group II, emergency bypass for therapy refractory vasospasm; group III, planned bypass surgery. Sixteen patients (35%) out of 46 were treated with emergency bypass. In group I (11 patients) mortality was 37% and a good outcome (GOS 4 & 5) was achieved in 36%. In group II (5 patients) mortality was 20% and good outcome was reached in 60%. In group III (30 patients) mortality was 10% and good outcome was achieved in 86.6%. Outcome was worse in patients with additional SAH. An emergency bypass procedure as part of the aneurysm treatment should be considered in risky situations. Accurate timely decision-making is crucial combined with a fast and secure bypass technique. Treatment of refractory vasospasm with emergency bypasses may help to improve outcome in selected patients.

[The role of projectional radiography in the detection of primary malignant and indeterminate bone neoplasms]. / Detektion von primär malignen und intermediären Knochentumoren: Wertigkeit der Projektionsradiographie.

PURPOSE: To evaluate the role of projectional radiography in the detection of primary and potentially malignant bone neoplasms. MATERIALS AND METHODS: We retrospectively reviewed the images and medical records of 80 patients (42 male, 38 female; range: 6 to 73 years; mean: 33 years) with pathologically proven primary or indeterminate bone tumors. RESULTS: The most common symptom was local pain (84 %). In 69 of 80 patients (86 %), projectional radiography was the first imaging modality, which correctly identified the malignant character of the bone lesion in 60 of these 69 patients (87 %). In 2 patients, bone neoplasms were overlooked due to diagnostically inadequte image quality. The false-diagnosis rate was not significantly different between board-certified radiologists working in hospitals and radiologists in outpatient facilities (p > 0.05). Bone tumors predominantly affecting adults, such as chondrosarcomas, needed a longer time for the diagnosis than bone tumors mainly found in childhood, such as osteosarcomas. The median age of patients with delayed imaging work-up because of attempted conservative therapy (45 years +/- 20 years) was significant higher than the median age of patients with immediate radiographic work-up (27 years +/- 16 years). CONCLUSION: Projectional radiography is the most common initial imaging method for bone pain and continues to play an important role to reduce the time gap between first onset of symptoms and definitive treatment. In unremitting focal bone pain, bone neoplasms should be taken into consideration not only in children but also in patients beyond adolescence.

Management of ruptured aneurysms combined with coexisting aneurysms.

In patients suffering from subarachnoid haemorrhage (SAH) and presenting with multiple intracranial aneurysms (MIA) two questions have to be decided on: 1st when is the ideal moment to eliminate the ruptured aneurysm and 2nd when to treat the coexisting aneurysms. In our series we retrospectively analysed 124 SAH-patients presenting with a total of 323 aneurysms. In 57 patients the ruptured aneurysm and all coexisting aneurysms were clipped during the first operation, whereas in 9 patients only some of the coexisting aneurysms (group-A; age in median 55 years) were clipped besides the ruptured one. In 55 patients (group-B; age in median 55 years) the first operation was restricted to clipping the ruptured aneurysm, dealing with the coexisting aneurysm subsequently. Immediately after admission 3 patients passed away. One of the 64 patients waiting (average 60 days, median 14 days) for the subsequent clipping of the not yet secured aneurysms suffered a SAH. Six to 12 months after the initial SAH, 78% of the cases in both groups reached a Glasgow Outcome Score of 4 or 5. Even if in patients with coexisting unruptured intracranial aneurysms the elimination of each and every aneurysm is recommended, the advantages of an unstaged procedure versus the additional strain caused by the prolongation of the procedure, e.g. approach over the midline, 2 or more craniotomies, and the risk of additional ischemic damage to the brain, caused by increased manipulation of cerebral arteries and brain tissue, have to be carefully considered. This is of special importance in dealing with patients in higher Hunt and Hess grades.

Basilar bifurcation aneurysms. Lessons learnt from 40 consecutive cases.

Basilar bifurcation aneurysms are lately treated frequently with endovascular technique. Microsurgical clipping occlusion technique has, however, still its solid position because of its completeness. This standard technique is required often due to unfeasibility and/or incompleteness at the time of application of the endovascular technique for aneurysms of this location. The authors suggest following strategies and tactics for safe and secure occlusion of aneurysms of this location: pterional approach, selective extradural anterior clinoidectomy SEAC, no transection of the posterior communicating artery, isolation of perforating arteries at the time of neck clipping with oxycellulose and combination of the use of fenestrated clip and conventional clip (especially for aneurysms projected posteriorly), controlled hypotension (systolic pressure of around 100 mmHg), temporary clipping (trapping) procedures of usually less than 15 min. All these are aimed for prevention of intraoperative premature rupture, and of injury of perforating arteries and for complete occlusion of aneurysms in the narrow depth of the operative field.

Three cases of AVM at eloquent areas finally treated with conventional microsurgical method.

Three special cases of AVM finally treated with conventional microsurgical method are presented. Two cases of medium sized AVMs were located at the central region, one of them was primarily treated with Gamma-knife followed by endovascular embolization having been complicated with growing cyst formation followed ultimately by microsurgical removal. The AVM of another case was embolized three times, followed by removal of the residual nidus under awake surgery. The third AVM located at the hypothalamus in the vicinity of the optic nerve was considered unsuitable for embolization and Gamma-knife therapy, and therefore removed by microsurgery using special approaches after a trial of embolization. In terms of microsurgical removal, preoperative embolization, embolization material, awake surgery and selection of special approaches are discussed.

Conventional microsurgical treatment of paraclinoid aneurysms: state of the art with the use of the selective extradural anterior clinoidectomy SEAC.

Surgical treatment of paraclinoid aneurysms is considered to be difficult due to their complicated anatomical location in the vicinity of important neural, vascular and bony structures. We present our clinical experience of the past 10 years of conventional microsurgical treatment of 81 paraclinoid aneurysms in 75 patients with the use of selective extradural anterior clinoidectomy SEAC and discuss the method of therapy option by reviewing recent reports on results of endovascular coiling method and the combination of these with conventional microsurgical therapy. The favorable surgical results with the use of SEAC and no recurrence of the treated aneurysm after clipping procedure in our series indicate that direct surgery can still be a standard technique for paraclinoid aneurysms in view of the fact that the endovascular aneurysm coiling methods are still associated with a considerable percentage of incomplete occlusion and present the problem of coil packing.

Experimental axonal injury triggers interleukin-6 mRNA, protein synthesis and release into cerebrospinal fluid.

Diffuse axonal injury is a frequent pathologic sequel of head trauma, which, despite its devastating consequences for the patients, remains to be fully elucidated. Here we studied the release of interleukin-6 (IL-6) into CSF and serum, as well as the expression of IL-6 messenger ribonucleic acid (mRNA) and protein in a weight drop model of axonal injury in the rat. The IL-6 activity was elevated in CSF within 1 hour and peaked between 2 and 4 hours, reaching maximal values of 82,108 pg/mL, and returned to control values after 24 hours. In serum, the levels of IL-6 remained below increased CSF levels and did not exceed 393 pg/mL. In situ hybridization demonstrated augmented IL-6 mRNA expression in several regions including cortical pyramidal cells, neurons in thalamic nuclei, and macrophages in the basal subarachnoid spaces. A weak constitutive expression of IL-6 protein was shown by immunohistochemical study in control brain. After injury, IL-6 increased at 1 hour and remained elevated through the first 24 hours, returning to normal afterward. Most cells producing IL-6 were cortical, thalamic, and hippocampal neurons as confirmed by staining for the neuronal marker NeuN. These results extend our previous studies showing IL-6 production in the cerebrospinal fluid of patients with severe head trauma and demonstrate that neurons are the main source of IL-6 after experimental axonal injury.

EEG reactivity in the prognosis of severe head injury.

We compared reactivity of EEG to external stimuli--an easily and quickly available measure--with the central conduction time (CCT) of the somatosensory evoked potentials, currently the most-used electrophysiologic method to predict outcome in severe head injury (SHI), and with the initial Glasgow Coma Scale (GCS) score. In 50 patients, comatose subsequent to SHI, we measured EEG reactivity and CCT within 48 to 72 hours and compared them with the outcome after 1.5 years. Using discriminant analysis, EEG reactivity correctly classified 92%, CCT classified 82%, and both measures together classified 98% of the patients into globally good or bad outcome groups. GCS allowed a correct classification in only 72% and, combined with either of the two electrophysiologic measures, did not further increase predictability. EEG reactivity is an excellent long-term global outcome predictor in SHI, superior to CCT and GCS. When the two electrophysiologic measures are combined, a prognostic accuracy is achieved that is better than that of any other reported method.

Comparison of functional and structural brain disturbances in Wilson's disease.

We assessed the functional and structural brain disturbances in Wilson's disease (WD) by evoked potentials (EPs) and magnetic resonance imaging (MRI). All the 25 neurologically symptomatic and 44% of the 16 asymptomatic patients, assessed by both EPs (n = 48) and imaging (n = 41), had at least 1 abnormality of either prolonged EP conduction times, imaging-outlined presence of cerebral lesions, or brain atrophy. Our findings indicate that EPs and MRI are sensitive techniques for the evaluation of brain involvement in WD.

Detectable concentrations of Fas ligand in cerebrospinal fluid after severe head injury.

When the cell surface molecule Fas is triggered by its agonist Fas ligand the result is apoptosis of these cells and tissue destruction. To elucidate the pathophysiological relevance of Fas ligand in patients with cerebral oedema caused by trauma, we examined its concentrations in cerebrospinal fluid in 18 patients using specific ELISA. Serum and cerebrospinal fluid from healthy people and injured patients without head trauma did not contain detectable Fas ligand. In contrast, cerebrospinal fluid from patients with severe brain injury contained high concentrations of Fas ligand without detectable concentrations in serum. Soluble Fas ligand concentrations in cerebrospinal fluid correlated significantly with severity of brain injury. The Fas-Fas ligand-system may have a pivotal role in causing oedema and local tissue destruction in the brain after severe head injury.

Intrathecal and serum interleukin-6 and the acute-phase response in patients with severe traumatic brain injuries.

Patients with severe traumatic brain injury (TBI) show a profound acute-phase response. Because interleukin-6 (IL-6) is an important mediator of these pathophysiological changes, IL-6 levels were monitored in the cerebrospinal fluid (CSF) and serum of 20 patients with severe isolated TBI. All patients received indwelling ventricular catheters for intracranial pressure monitoring and for release of CSF when intracranial pressure exceeded 15 mmHg. CSF and blood samples were drawn daily for up to 14 days. The CSF/serum albumin ratio (QA) served as a parameter of blood brain barrier dysfunction. Differential blood counts as well as the acute-phase proteins C-reactive protein, alpha 1-antitrypsin, and fibrinogen were recorded. IL-6 was detected in all CSF samples and reached values of up to 31,000 pg/mL, while serum levels remained significantly lower (alpha < or = .01) and never exceeded 1,100 pg/mL the entire study period. A correlation between CSF and serum IL-6 was found initially after the trauma and corresponded to a severe dysfunction of the blood brain barrier (r = .637, p = .001). Maximum IL-6 concentrations in serum correlated with peak levels of acute-phase proteins (C-reactive protein, alpha 1-antitrypsin, and fibrinogen). With regard to blood cell count, an initial leukocytosis combined with a borderline lymphocytopenia was observed. Thrombocytes decreased to a subnormal level during the first few days, but reached supranormal numbers by the end of the study period. Our results show that the increase of IL-6 levels in CSF and serum is followed by a profound acute-phase response in patients with TBI. Because cytokine concentrations are significantly lower in serum compared with CSF, we hypothesize that IL-6 produced in the central nervous system may play a role in initiating the acute-phase response.

Subchondral bone and cartilage disease: a rediscovered functional unit.

The role of subchondral bone in the pathogenesis of cartilage damage has likely been underestimated. Subchondral bone is not only an important shock absorber, but it may also be important for cartilage metabolism. Contrary to many drawings and published reports, the subchondral region is highly vascularized and vulnerable. Its terminal vessels have, in part, direct contact with the deepest hyaline cartilage layer. The perfusion of these vessels accounts for more than 50% of the glucose, oxygen, and water requirements of cartilage. Bony structure, local metabolism, hemodynamics, and vascularization of the subchondral region differ within a single joint and from one joint to another. Owing to these differences, repetitive, chronic overloading or perfusion abnormalities may result in no pathological reaction at all in one joint, while in another joint, these same conditions may lead to osteonecrosis, osteochondritis dissecans, or degenerative changes. According to this common etiological root, similar pathological reactions beginning with marrow edema and necrosis and followed by bone and cartilage fractures, joint deformity, and insufficient healing processes are found in osteonecrosis, osteochondritis dissecans, and degenerative disease as well.

Magnetic resonance imaging of articular cartilage and evaluation of cartilage disease.

Clinical magnetic resonance imaging of articular cartilage is possible by using techniques that offer high contrast between articular cartilage and adjacent structures in reasonable examination times. The fat-suppressed, three-dimensional, spoiled gradient-echo sequence has been reported to be accurate and reliable, and the addition of this sequence to a routine examination does not significantly compromise patient throughput. Fast spin-echo imaging also shows promise in the clinical evaluation of articular cartilage, because the newer, stronger-gradient systems allow thinner slice acquisition with two-dimensional sequences. Together, these sequences allow the evaluation of intrachondral lesions and surface defects. Furthermore, quantitative measurements of cartilage volume for follow-up studies are possible with the use of the fat-suppressed, three-dimensional, spoiled gradient-echo sequence.