SponDT (Spondylodiscitis Diagnosis and Treatment): spondylodiscitis scoring system.

BACKGROUND: Spondylodiscitis is a chameleon among infectious diseases due to the lack of specific symptoms with which it is associated. It is nevertheless a serious infection, with 7% mortality of hospitalized patients, in large part because of delayed diagnosis. The aim of this study was to develop a diagnosis and course-of-disease index to optimize its treatment. MATERIAL AND METHODS: Through analysis of 296 patients between January 1998 and December 2013, we developed a scoring system for spondylodiscitis, which we term SponDT (Spondylodiscitis Diagnosis and Treatment) based on three traits: (1) the inflammatory marker C-reactive protein (CRP) (mg/dl), (2) pain according to a numeric rating scale (NRS) and (3) magnetic resonance imaging (MRI), to monitor its progression following treatment. RESULTS: The number of patients receiving treatment increased over the past 15 years of our study. We also found an increasing age of patients at the point of diagnosis across the study, with an average age of 67.7 years. In 34% of patients, spondylodiscitis developed spontaneously. Almost 70% of them did not receive treatment until the first diagnosis using SponDT. Following treatment against spondylodiscitis, pain intensity decreased from 6.0 to 3.1 NRS. The inflammatory markers also decreased (CRP from 119.2 to 46.7 mg/dl). Similarly, MRI revealed a regression in inflammation following treatment. By employing SponDT, patients were diagnosed and entered into treatment with a score of 5.6 (severe spondylodiscitis) and discharged with a score of 2.4 (light/healed spondylodiscitis). CONCLUSION: SponDT can be used to support the diagnosis of spondylodiscitis, particularly in patients suffering from back pain and elevated levels of inflammation, and can be used during the course of treatment to optimize control of therapy. LEVEL OF EVIDENCE: IIa-evidence from at least one well-designed controlled trial which is not randomized.

[Therapy of Spondylodiscitis by Severity]. / Die schweregradorientierte Therapie der Spondylodiszitis ­ eine prospektive Betrachtung anhand von elektronisch basierten Behandlungspfaden.

Spondylodiscitis is a rare but serious infection of the spine. Recognised methods of treatment include immobilisation and systemic antibiotics. However, available data for specific and recommendations for continuing treatment are also rare. The aim of the present study is the optimisation of the therapy of spondylodiscitis using a clinical pathway that depends on a classification of spondylodiscitis. From 1 October 1998 to 31 December 2013, a classification of the severity of spondylodiscitis was established, including specific treatment recommendations. As part of the re-evaluation, the classification of severity was adapted. On this basis, electronically based clinical pathways were developed. A total of 296 cases were included. With a steadily increasing number of treatments, the mean age of the patients increased to 67.3 years. In 34.3% of these patients, spondylodiscitis developed spontaneously and 68.6% of patients did not receive treatment until the diagnosis. In the context of the specific treatment, pain intensity decreased from 6.0 to 3.1 NRS (numeric rating scale). The inflammatory values (CRP) decreased from 119.2 to 46.7 mg/dl. The time from the onset of symptoms to the surgical treatment was almost 65.6 days and has not changed significantly. Nevertheless, the time from admission to surgical treatment could be reduced to less than 3 days. The classification of patients into 3 degrees of severity of spondylodiscitis (SSC) depends on the SponDT: spondylodiscitis diagnosis and treatment. The SponDT describes vertebral destruction and the current neurological status. The severity-adapted therapy was mapped electronically and includes specific surgical care, systemic antibiotic therapy and physical therapy.

Cyclical mechanical stretch modulates expression of collagen I and collagen III by PKC and tyrosine kinase in cardiac fibroblasts.

Mechanical load and chemical factors as stimuli for the different pattern of the extracellular matrix (ECM) could be responsible for cardiac dysfunction. Since fibroblasts can both synthesize and degrade ECM, ventricular fibroblasts from adult rat hearts underwent cyclical mechanical stretch (CMS; 0.33 Hz) by three different elongations (3%, 6%, 9%) and four different serum concentrations (0%, 0.5%, 5%, 10%) within 24 h. Expression of collagen I and III, as well as matrix metalloproteinase-2 (MMP-2), tissue inhibitor of MMP-2 (TIMP-2), and colligin were analyzed by RNase protection assay. In the absence of serum, 9% CMS increased the mRNA of collagen I by 1.70-fold and collagen III by 1.64-fold. This increase was prevented by the inhibition either of PKC or of tyrosine kinase but not of PKA. Inhibition of PKC or tyrosine kinase itself reduced the expression of collagen I and collagen III mRNA. The mRNA of MMP-2, TIMP-2, and colligin showed the same tendency by stretch. Combined with 10% serum, 6% CMS reduced the mRNA of collagen I (0.62-fold) and collagen III (0.79-fold). Inhibition of PKC or tyrosine kinase, but not of PKA, prevented the reduction of collagen I and collagen III mRNA in 10% serum. The results show that the response of fibroblasts to CMS depends on the serum concentration. At least two signaling pathways are involved in the stretch-induced ECM regulation. Myocardial fibrosis due to ECM remodeling contributes to the dysfunction of the failing heart, which might be attributed to changes in hemodynamic loading.

Cardiac remodeling in erythropoietin-transgenic mice.

BACKGROUND: Transgenic (tg) mice with chronic overexpression of the human erythropoietin gene are characterized by an increased hematocrit of about 0.80 in adulthood. This is accompanied by cardiac dysfunction and premature death. The aim of this study was to examine whether this cardiac dysfunction was accompanied by hypertrophy of the heart with remodeling of the extracellular matrix (ECM). METHODS: 3-months-old wild type (wt) and tg mice without cardiac hypertrophy were compared with the respective 7-months-old mice. The mRNA of brain natriuretic peptide (BNP), of the matrix metalloproteinases (MMP)-2, -8, -9, -13, of the tissue inhibitor of metalloproteinase (TIMP)-1, -2, -3, -4 and of collagen I and III was detected by ribonuclease protection assay. The activity of MMPs was measured by zymography. RESULTS: There was hypertrophy of both ventricles in 7-months-old tg mice, which was accompanied by elevated mRNA expression of BNP. MMP-2 activity was increased and MMP-9 activity was decreased in the left ventricle (LV) of 3-months-old tg mice. This was accompanied by elevated TIMP-4 expression, followed by a shift of collagen mRNA expression from type III to type I in this ventricle. CONCLUSION: The shift to collagen I in the heart of tg mice might be associated with a stiffer ventricle resulting in diastolic dysfunction. This may be responsible for a relative and intermittent LV- and right ventricle (RV)-insufficiency which was likely to have occurred as evidenced by the elevation of lung and liver weight with hemorrhage and interstitial fibrosis after 7 months.

Norepinephrine-induced changes in cardiac transforming growth factor-beta isoform expression pattern of female and male rats.

Transforming growth factor-beta (TGF-beta) is a ubiquitous growth-regulating protein with an essential role in tissue repair and formation of extracellular matrix (ECM). To better understand the role of different isoforms of TGF-beta in the cardiac remodeling process induced by norepinephrine (NE), the expression of TGF-beta1, TGF-beta2, and TGF-beta3 was studied and compared with the expression of collagen. NE (0.1 mg/kg. h) was intravenously infused in female and male Sprague-Dawley rats for several time periods, and freshly obtained ventricular myocardium after 1 day was dissociated into myocyte and nonmyocyte fractions. Prazosin (0.1 mg/kg x h) and metoprolol (1 mg/kg. h) were used to block alpha- and beta-adrenoceptors, respectively. After NE infusion, the three isoforms of TGF-beta were differentially induced as far as the magnitude and the time course is concerned. The increased expression of TGF-beta2 started earlier with a maximum after 12 hours and was more pronounced (10-fold elevation) than that of the other two isoforms, with a clear specificity for the left ventricle in female hearts. This specificity was also seen in male rats with 16-fold elevation of TGF-beta2 after 1 day of NE-stimulation. The increase of TGF-beta2 was significant only in the myocyte fraction obtained from female as well as from male hearts. The expression of the mRNA of all TGF-beta isoforms of collagen type I and type III, and of the matrix metalloproteinase (MMP)-2 and its inhibitor TIMP-2 was reduced predominantly by alpha-adrenoceptor blockade with prazosin. The increase in TGF-beta isoforms correlated with that of the mRNA expression of collagens, MMP-2 and TIMP-2.