Pharmacoeconomical consequences of postoperative CSF leaks after intracranial surgery--a prospective analysis.

Cerebrospinal fluid (CSF) leaks are well-known and frequent complications of intracranial procedures with their clinical aspects covered by numerous studies. Little, however, is known about the pharmacoeconomical aspects of this specific complication. 545 patients with a variety of intracranial procedures (elective and trauma) were recruited for a multicenter, prospective, observational study over a 13-month period. A specific pharmacoeconomic analysis was performed in 168 of these patients from the institution of the first author covering all clinical and pharmaco-economical aspects of this specific complication. Of all patients, 5.36% developed a postoperative CSF leak. Treatment of the leak required numerous diagnostic and therapeutic procedures such as reoperations (n = 6), lumbar punctures (n = 11) or lumbar drainages (n = 4). Costs for these procedures and prolonged hospital stays nearly doubled the costs per case (€14079/case without a fistula vs. €25499/case with a fistula). Reimbursement for the hospital covered these extra costs, but net earnings per case were diminished by €565 in cases with a CSF leak. The authors conclude that the presence of a CSF leak after an intracranial operation - although not influencing outcome in general - results in additional diagnostic and therapeutic procedures for the patient, an enormous increase in costs for the community, and a financial loss for the hospital. Strategies to lower this complication rate should therefore urgently be developed both from a clinical and a pharmacoeconomical point of view.

Prospective studies in patients with intraventricular haemorrhage without the capacity to give consent in Germany--a legal dilemma.

OBJECTIVE: The prognosis of intracranial haemorrhage with ventricular participation is poor. The acute onset of hydrocephalus has to be treated with an external ventricular drainage. However, intraventricular blood clots often obstruct the drainage catheter; the reinsertion is usually associated with an increased risk of complications. Therefore, intraventricular thrombolysis using recombinant tissue plasminogen activator (rt-PA), urokinase or streptokinase has been performed in several cases. In Germany, rt-PA does not have approval for intraventricular applications, and the risks and benefits of this treatment are as yet unclear. Several authors recommend its use only in the frame of prospective studies, meaning that intraventricular administration of thrombolytic agents within an individual therapy trial could be viewed as medical malpractice. METHODS: We designed a national prospective randomised and controlled study in patients with intraventricular haemorrhage to investigate the risks and effects of intraventricular rt-PA treatment. The local ethics committee and lawyers did not accept the study protocol due to a non-acceptable risk of complications. In two further conferences, the risk of undertreatment in the control group was a major reason not to accept the protocol. We discuss the conflicts of law in related studies. CONCLUSIONS: There is a need for a solution to the legal conflicts of medical malpractice, unclear risk-benefit ratio and unfeasibility due to risk of complications or undertreatment in studies with patients without the capacity to give informed consent.

[Familial cavernous malformations of the central nervous system. A clinical and genetic study of 15 German families]. / Familiäre Kavernome des Zentralnervensystems. Eine klinische und genetische Studie an 15 deutsche Familien.

In 1928, Hugo Friedrich Kufs reported on a family with cerebral, retinal, and cutaneous cavernous malformations. Since then, more than 300 families with inherited cavernous malformations have been reported. Genetic studies showed three loci, on chromosomes 7q21-q22 (with the gene CCM1), 7p15-p13 (CCM2), and 3q25.2-q27 (CCM3). The gene product of CCM1 is Krit 1 (Krev interaction trapped 1), a protein interacting with angiogenesis by various mechanisms. Recently, CCM2 has also been identified; its product is a protein which might have a function similar to that of Krit 1. However, the CCM3 gene has still not been found. In this study, we present clinical and genetic findings on 15 German families.

Rapid manifestation of cervical vertebral osteomyelitis.

Within 10 days after cystoscopy causing urosepsis this patient developed persistant neckpain as initial symptom of vertebral osteomyelitis. E. coli was isolated from urine, blood cultures and later from bone biopsy. Antibiotic treatment did not stop the progress of the disease. A transverse spinal cord syndrome occurred due to a pathological fracture of C5 and C6 and operative decompression was necessary. The rapid onset of osteomyelitis was impressive. For effective treatment of bacterial osteomyelitis a bone biopsy is sometimes unavoidable and indicated.

G-CSF application in patients with severe bacterial pneumonia increases IL-10 expression in neutrophils.

In severe pneumonia, the application of granulocyte-colony stimulating factor (G-CSF) was associated with reduced complications possibly by an induction of anti-inflammatory cytokines. It is not clear, whether G-CSF induces interleukin-10 (IL-10) synthesis in neutrophils. In a randomized study, 15 patients with severe community acquired pneumonia were treated either by a single dose of G-CSF and antibiotic therapy (n=8) or antibiotics alone (n=7). Messenger ribonucleic acid (mRNA) expression of IL-10 and tumor necrosis factor alpha of peripheral blood leukocytes was measured using in-situ hybridization (ISH) and reverse-transcription-polymerase-chain-reaction (RT-PCR). In addition, the cytokine release of lipopolysaccharide (LPS)-stimulated whole blood was measured by ELISA. We detected increased IL-10 mRNA by ISH (140 +/- 8% vs. -11 +/- 5%, P<0.01) and RT-PCR (126 +/- 16% vs. -28 +/- 3%, P<0.01) in the G-CSF-treated group only. In contrast, LPS-stimulated whole blood cells in vitro released significantly less IL-10 compared to the control group (-38.2 +/- 97 vs. -14.8 +/- 6 pg/ml, P<0.02). There was no significant effect on IL-10 serum protein levels and the TNF-alpha release and expression. IL-10 mRNA was detected predominantly in cluster designation 66b (CD66b) positive nucleated blood cells indicating that polymorphonuclear leukocytes are the main source of IL-10 expression after G-CSF stimulation. G-CSF induces transcription of IL-10 mRNA in neutrophils without increased release. This may be due to posttranscriptional effects.