[Is there a magic bullet for sarcomas? : Personalised treatment for maligant tumours of bone and soft tissue]. / Gibt es eine Magic Bullet für Sarkome? : Personalisierte Therapie von malignen Tumoren des Stütz- und Bewegungsapparates.

BACKGROUND: Personalised tumour therapies aim to selectively target pathways and structures to which a tumour shows an oncogenic addiction. OBJECTIVE AND METHOD: This article aims to provide an overview of relevant genetic alterations in bone and soft-tissue tumours, which might serve as potential therapeutic targets for personalised medicines in the future. Recent approaches towards a personalised treatment of various tumours of bone and soft tissues are reviewed. RESULTS: Molecular diagnosis has become an essential tool for the characterisation of bone and soft-tissue tumours. Currently, no targeted therapies are routinely available for bone sarcomas. Denosumab is merely a symptomatic treatment for giant cell tumours of the bone. Imatinib has become the paradigm of a targeted treatment for subgroups of malignant gastrointestinal stromal tumours (GISTs) and dermatofibrosarcoma protuberans. Antiangiogenic multikinase inhibitors, various other tyrosine kinase inhibitors (TKIs) and monoclonal antibodies are currently being evaluated in several (sub-)types of soft-tissue sarcomas. Sorafenib showed promising results in the treatment of aggressive desmoid-type fibromatosis. Histology-tailored chemotherapies did not yield superior results in a prospective randomised multicentre trial. CONCLUSION: More in-depth knowledge is required for many sarcomas to link their genetic alterations to tumorigenesis in order to develop efficient personalised treatment strategies. Clinical trial designs need to be adapted to evaluate new therapeutic strategies in these ultra-rare tumours and their various sub-types more efficaciously.

[Silver coating on tumour prostheses]. / Silberbeschichtung auf Tumorendoprothesen.

BACKGROUND: Modular endoprostheses, so-called "tumour or megaprostheses" are mainly used for limb salvage surgery after resection of malignant soft tissue or a bone tumour. Sometimes, this type of prosthesis is also used for revision surgeries after failed primary joint arthroplasty. Despite continuously improving techniques and quality management systems, periprosthetic infection is one of the most serious complications. AIM OF THE STUDY: Review of the literature in the PubMed data base with the main focus on silver coatings in joint arthroplasty and their effect on infection rate, outcome and patients' safety. RESULTS: The current literature shows that there is a beneficial role of silver coatings in megaprostheses in terms of revision rates for septic complications, especially following tumour resection with bad soft tissue coverage or in (multimorbid) high-risk patients, compared to uncoated implants. DISCUSSION: Based on the results of previous publications examining blood or serum silver concentrations or silver levels in urine, silver coatings do not appear to have side effects, except for local argyria. Continuous monitoring of silver levels in blood or serum is still recommended, and additional long-term studies will be necessary to verify the effectiveness and safety of silver coatings.

Intraarticular synovial sarcoma of the knee rising from a lateral meniscus - a case report.

Synovial sarcoma (SS) is a rare mesenchymal tumor, accounting less than 10% of soft tissue sarcomas. We report a case of intraarticular SS mimicking nodular synovitis and lateral meniscus rupture. Due to clinical and radiological presentation, arthroscopic synovectomy was performed, and histology confirmed nodular synovitis. After four years the lesion recurred and new arthroscopic biopsy was performed, revealing a monophasic SS with SYT/SSX1 translocation. Repeated histology of the first specimen confirmed appearance of a nodular synovitis microscopically, with no morphological criteria for a sarcoma, but molecular analysis showed positive SYT/SSX1 translocation. Wide extraarticular knee resection and reconstruction with a tumor megaendoprosthesis-allograft composite was performed with a negative tumor margins. This case report showed that in a case of benign histological appearance, underlying sarcoma is possible and could be identified in early stages only with an advanced pathology methods. LEVEL OF EVIDENCE: Level IV historical case.

Could nasal septal deformities type 5 and 6 be a predictive factor of the indi- vidual genetic predilection for the onset of an acute coronary syndrome?.

OBJECTIVES: the possible impact of nasal septal deformities (SD) on cardiac pathology has not been well studied, despite growing evidence among data showing that upper air-way obstruction has a negative effect on cardiac function in general and a "deviated nasal septum" being considered one of the most frequent factors responsible for impaired nasal breathing. METHODS: a retrospective, case-control, double-blind study was performed on 249 patients who survived an acute coronary syndrome (ACS) attack. All patients underwent coronary angiography and were divided into coronary angiography positive (123 pts) and coronary angiography negative (126 pts) groups. The quality of nasal breathing was not considered in this study, but morphological aspects of the nasal septum (nasal septal deformities) were observed by anterior native rhinoscopy and endoscopic examination of the nose following the application of superficial anaesthesia. Mladina classification of nasal septal deformities was used. RESULTS: there was a statistically significant difference between coronary angiography negative and positive patients in Mladina type 1 to Mladina type 7 groups (p=0.000, X²=54.605). The incidence of nasal SD types 5 and 6 was higher in the group of ACS patients with the positive coronary angiography, whereas general distribution of the particular types of nasal septal deformities as they appear in the general population was found in the coronary angiography negative group. CONCLUSION: the fact that types 5 and 6 are inherited deformities and not related to trauma against the nose suggests the possible genetic predisposition for the onset of ACS with positive coronary angiography.

Lower limb salvage surgery: modular endoprosthesis in bone tumour treatment.

We retrospectively analysed 90 patients who underwent "en bloc" resection and modular endoprosthesis reconstruction in the lower limbs between 1987-2003. After proximal femur resection, reconstruction was performed with a modular endoprosthesis by Howmedica (KFTR, designed by Kotz) and modular revision endoprosthesis by W. Link or Lima-Lto (Revision system, designed by Wagner). The knee joint was reconstructed with a modular endoprosthesis (Howmedica, KFTR designed by Kotz) after distal femur or proximal tibia resection. Malignant bone tumours were present in 58 patients (64.5%), benign tumours in 16 (17.8%), metastases in 8 (8.9%), tumour-like lesions in 4 (4.4 %) and non-tumour-related destruction of the femur in 4 patients (4.4%). High-grade tumours were found in the majority of malignant bone tumours (70.7%). Treatment complications, which occurred in 26 patients, were: local recurrence of the tumour, deep infection, acetabular destruction following hemiarthroplasty, recurrent dislocations of endoprosthesis, periprosthetic fracture and hardware problems. In total, 23 patients (25.6%) died due to tumours. Endoprostheses should be considered as a treatment of choice for bone tumours in the hip and knee joint region. Advances in limb salvage surgery are, and will long continue to be, a great challenge for orthopaedic oncologists of the 21st century.

An open-label study investigating the efficacy and safety of 12-96 weeks of telmisartan treatment in patients with hypertension.

This open-label, multicentre, multinational trial evaluated the efficacy and safety of telmisartan used alone or as add-on therapy in 2121 adults with mild-to-moderate essential hypertension. Patients received telmisartan 40-80 mg once daily for 12 weeks and could participate in the study for up to 96 weeks, or until a marketed supply of telmisartan became available. Mean change from baseline in mean seated trough diastolic blood pressure (DBP) after 12 weeks' treatment, the primary endpoint, was -11.8 mmHg in the intent-to-treat population. The corresponding mean change in mean seated trough systolic blood pressure (SBP) was -20.2 mmHg. Both changes were statistically significant. Mean DBP and SBP reductions were apparent from week 4 and maintained throughout the treatment period. Telmisartan was well tolerated; the most common adverse events were headache (6%) and dizziness (3%), and 10% of adverse events were considered drug-related. In conclusion, telmisartan is an effective and well-tolerated drug when used as monotherapy or add-on treatment in this broad population of patients.

Clinical and echocardiographic features of two large left atrial parietal thrombi.

A 62-year-old woman with severe mitral stenosis and two large parietal thrombi inside the left atrium is described. The patient was admitted to the hospital because of heart failure. Transthoracic and transesophageal echocardiography showed a severe calcific mitral stenosis and two large (56.9 and 46.2 mm in diameter) parietal thrombi inside the left atrium attached to the interatrial septum and associated with severe spontaneous echo contrast. This severe spontaneous echo contrast was detected in the left atrium and in the left atrial appendage. The patient was referred for cardiac surgery. The two large parietal thrombi were removed, and the valve was replaced with a Sorin-Bicarbon mitral valve prosthesis. Intraoperative transesophageal echocardiography after replacement of the mitral valve prosthesis and removal of the thrombotic mass showed absence of any spontaneous echo contrast in the left atrium and in the left atrial appendage. This report describes the diagnostic approach and successful surgical treatment of two very large parietal thrombi inside the left atrium associated with severe mitral stenosis and atrial fibrillation, which is a rare occurrence.

Serum total, LDL, HDL cholesterol and triglycerides related to age, gender and cigarette smoking in patients with first acute myocardial infarction.

The aim of this study was to examine relationships between total cholesterol, LDL, HDL cholesterol, triglycerides and age, gender, and cigarette smoking in 190 patients (132 men and 58 women) aged 34-87 years with first AMI. The control group included 103 patients (57 men and 46 women) aged 29-90 years without a history of angina pectoris or AMI. High total cholesterol (over 5.2 mmol/L) was observed in 75% of patients with AMI vs. 48% of patients in the control group (p < 0.001). Patients with AMI had significantly higher total cholesterol and LDL cholesterol levels than controls (p < 0.0001). HDL cholesterol levels were significantly lower among patients with AMI than among the control group patients (p < 0.0001). Serum total cholesterol and LDL cholesterol is higher in patients with AMI up to 60 years old, but lower in patients older than 60 years. Women aged less than 50 years had significantly higher HDL cholesterol (p < 0.001), lower LDL cholesterol (p < 0.001), and lower total cholesterol (p < 0.05) than those over 50 years. Smokers with AMI who smoked over 20 cigarettes per day had significantly higher total cholesterol, LDL cholesterol and triglycerides levels than the non-smokers (p < 0.05). These findings suggest important influences of hyperlipoproteinemia and cigarette smoking upon development of myocardial infarction, especially in younger patients.

Incidence and hospital mortality of acute coronary artery disease among civilians in Zagreb during air-raid alarms.

During the period of air-raid alarms in Zagreb (September 1991), the influence of war-induced stress on the incidence and mortality of acute coronary artery disease was investigated. Control periods were September 1989 and September 1990. Among 2903 patients admitted to Emergency Care Units, 369 (13%) were examined for suspect acute coronary artery disease. During the same periods in 1989 and 1990, 10% and 11% of acute coronary artery disease patients were recorded, respectively. The percentage of patients with myocardial infarction or unstable angina, admitted to Coronary Care Units during September 1989, 1990 and 1991, was 49%, 50% and 55%, respectively. The number of Q myocardial patients admitted during September 1991 was significantly higher than that recorded during the same period in 1990. The incidence and mortality patterns in acute coronary artery disease patients were also examined during August, September and October 1991. The peak incidence of acute coronary artery disease was found in the first half of September, while the peak mortality in these patients was found during the second half of September. During the second half of September of 1989, 1990 and 1991, the mortality in Q myocardial patients in Coronary Care Units, was 16.7%, 15.2% and 23.8%, respectively. Besides the war-induced stress, transportation of our patients to shelters or inner parts of the hospital caused additional stress, probably contributing to the development of refractory malignant arrhythmia or heart failure.

Comparison of the postoperative fibrinogen, alpha-1-antitrypsin and alpha-2- macroglobulin concentrations in the blood of wounded soldiers of Croatian Army and peacetime injured civilians.

In 10 wounded Croatian Army soldiers and in 10 civilians with accidental musculosceletal traumatisation, blood concentrations of the 3 acute phase proteins: fibrinogen, alpha-1-antitrypsin and alpha-2-macroglobulin on the 1st, 5th and 10th postoperative day were assessed. On the 5th day after injury, increased concentrations of all 3 acute phase proteins (APP) were found in all patients. The rise of the fibrinogen concentrations in the wounded soldiers was the steepest. On the 10th day after wounding, fibrinogen concentrations in the gorup of wounded soldiers were significantly lower than those in the group of injured civilians. On the 10th day after wounding there were no differences between the 2 groups in the concentrations of alpha-1-antitrypsin and of alpha-2-macroglobulin. The lower fibrinogen concentrations in the wounded soldiers could be explained by the modulation of the general reactivity of the organism to injury, proposed by Woloski, which is induced by stress and microtrauma on battlefield before the wounding.

The value of the QRS scoring system in assessing regional and global left ventricular ejection fraction early after myocardial infarction.

In 71 patients with a myocardial infarction (MI) (anterior in 27, inferior in 44 patients) global (GEF) and regional (REF) left ventricular ejection fractions were determined by radionuclide ventriculography and estimated from a 12 lead electrocardiogram (ECG), using Selvester's QRS score, during the early phase of a MI (15 to 21 days following MI). Global ejection fractions determined by radionuclide ventriculography and from ECG using Palmeri's method were: for all MI 40.8 +/- 12.6% vs 39.6 +/- 11.4%; in the group of anterior MI 32.0 +/- 10.0% vs 30.0 +/- 9.7% and in the group of inferior MI 48.9 +/- 12.0% vs 45.1 +/- 8.2%. A good correlation was found between global ejection fractions determined by radionuclide ventriculography and ECG, as well as between radionuclide GEF and ECG score. A weaker correlation was found between radionuclide GEF and enzymes among all MIs and in the group of anterior MI, while in the group of inferior MI this correlation was insignificant. The analysis of REF determined by radionuclide ventriculography and ECG showed the greatest abnormalities in the infarct region, but in the group of anterior MI, dysfunction was present in the whole left ventricle. The comparison of infarct-related REF derived from radionuclide ventriculography, with the QRS score showed a significantly higher correlation than the comparison with enzymes. ECG estimation of REF from a modified Palmeri's equation showed a better correlation with radionuclide REF than did GEF derived from the standard Palmeri's equation: anterior MI; r = 0.90 vs r = 0.82, inferior MI; r = 0.84 vs r = 0.69, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

[Thrombolytic therapy in acute myocardial infarct in 1992]. / Tromboliticka terapija u akutnom infarktu miokarda (stanje 1992. godine).

The management of acute myocardial infarction has dramatically changed in the last decade. The conservative approach with bed rest, oxygen therapy, pain relief and prevention of complications--the former cornerstones of the treatment of acute myocardial infarction--are now being replaced with new, more aggressive forms of therapy, including early administration of thrombolytic agents. With the more than 100,000 patients studied in various clinical trials in the different parts of the world, the use of thrombolytic therapy is probably the most thoroughly studied medical intervention in human medical history. The results of these trials undoubtedly showed that thrombolytic therapy had a major impact on reducing mortality and preserving left ventricular function in patients with acute myocardial infarction. The purpose of this article is to review current new information on thrombogenesis and thrombolysis, the indications and contraindications of thrombolytic therapy, comparisons between different thrombolytic agents and the role of adjuvant antithrombotic therapy.

Global and regional parameters of left ventricular performance in healthy subjects during rest and exercise assessed by radionuclide ventriculography.

The aim of our study was to analyze numerous global and regional parameters of left ventricular (LV) performance during rest and exercise, in the group of 14 healthy subjects, by quantitative gated equilibrium ventriculography in left anterior oblique view (45 degrees). The global LV parameters at rest vs. exercise in our study were: heart rate 68.9 +/- 18.4 vs. 137.5 +/- 38.6; systolic blood pressure (mmHg) 121.8 +/- 18.2 vs. 178.6 +/- 31.2; diastolic blood pressure (mmHg) 82.1 +/- 10.8 vs. 90.7 +/- 12.4; double product 8,368.6 +/- 2,308.8 vs. 24,589.3 +/- 8,357.8; global ejection fraction (%) 61.9 +/- 15.4 vs. 72.8 +/- 12.8, end-diastolic volume index (ml/m2) 82.5 +/- 23.2 vs. 96.9 +/- 27.8; end-systolic volume index (ml/m2) 31.8 +/- 19.8 vs. 26.9 +/- 15.4; stroke volume index (ml/m2) 50.6 +/- 17.6 vs. 70.0 +/- 22.6; peak emptying rate (EDV/s) 3.4 +/- 2.6 vs. 8.3 +/- 3.8 and peak filling rate (EDV/s) 3.6 +/- 2.6 vs. 9.6 +/- 3.8. A significant difference (p < 0.05) between rest and exercise was found for all parameters. The highest values of LV regional ejection fraction were found in anterolateral and posterolateral region, while the lowest values were observed in inferoseptal and inferior regions. During exercise a significant increase of regional ejection fraction was found in all regions. The highest percent of radius shortening during rest was in anterolateral and posterolateral regions, and lowest in inferoseptal and inferior regions. The same sequence was found during exercise, and the difference in percent of radius shortening, between rest and exercise was significant in all regions. The observed normal values of global and regional parameters of LV function during rest may serve as a contribution for referent values. Our results on regional ejection fraction and the percent of radius shortening in rest, and their change during exercise, offer the possibility of additional information in the investigation of cardiac patients by means of radionuclide ventriculography.

Hyperdynamic beta-adrenergic syndrome among Croatian soldiers engaged in battle.

A group of 1592 male Croatian soldiers (average age 32 +/- 9, ranging from 19 to 54) were examined by an internist at the war hospital. Elevated blood pressure was found in 80 men (5%); 61 of them had no history of hypertension (Group A), while in 19 patients hypertensive disease had been diagnosed before (Group B). In group A, systolic blood pressure (BPS in mm Hg), diastolic blood pressure (BPD in mm Hg) and heart rate (HR) were 182 +/- 13, 111 +/- 10, and 115 +/- 9; in group B, the values were 184 +/- 12, 108 +/- 8, 85 +/- 11. Electrocardiograms (ECG) and thorax roentgenograms of group A did not reveal any hypertension-caused signs, neither did the examination of the fundus, nor the serum creatinine values yield any abnormal results. The ECG test showed sinus tachycardia (heart rate > 100/min) but an otherwise normal function in group A. In group B, at least one of the laboratory examinations confirmed the previously diagnosed hypertension. Group A was treated with the cardioselective beta-blocker Atenolol (100 mg daily), while in group B, the previous antihypertensive medication was modified and/or increased. All patients were sent back to the front-line. Three days later, blood pressure and heart rate in group A were: BPS 139 +/- 9, BPD 87 +/- 6 and HR 77 +/- 8; and in group B: 156 +/- 11, 95 +/- 8, 75 +/- 7. A significant decrease in systolic and diastolic blood pressure (p < 0.0001) was found in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Regression of ECG signs of myocardial infarction related to infarct size and left ventricular function.

Quantitative and qualitative analyses of Q waves and QRS scores were performed on 69 patients during the early phase of first myocardial infarction (MI) and 6 months subsequently. The regression of ECG signs of MI were compared with the enzymatically estimated size of MI, the location of MI, and with the changes of global ejection fraction (GEF) assessed by radionuclide ventriculography. Among 57 patients with Q wave MI a complete disappearance of ECG signs of MI was found in 9 (15.7%). Patients with MI of inferior location showed a significantly higher reduction of Q waves (p < 0.001) and QRS scores (p < 0.001) than the anterior MI group. In the group of 12 patients with non Q wave MI, 11 demonstrated complete regression of MI signs. Among all Q wave and non Q wave MIs, the authors found no significant difference in the size of MI between patients with and without complete regression of ECG signs of MI. The median of the percent of change of the QRS score was significantly higher (p = 0.04) in the group of patients with improved GEFs than in the group of patients with decreased or unchanged GEFs 6 months following acute MI. The sensitivity, specificity, and predictive values for improved left ventricular function according to the change of Q waves and ECG scores were 91%, 32%, and 62%; for changes of Q waves, 81%, 40%, and 63%; and for changes of ECG scores, 91%, 36%, and 64%, respectively. In the group of patients with non Q wave MI these values were 100%, 50%, and 91% as a result of ST-T disappearance.

[The effect of war-induced stress in Croatia on the incidence and mortality of acute ischemic heart disease]. / Der Einfluss des kriegsbedingten Stresses in Kroatien auf die Häufigkeit und Mortalität der akuten ischämischen Herzkrankheit.

During war operations in Croatia and air alarms in Zagreb, a significantly higher incidence of patients with acute coronary artery disease was registered. Higher incidence of patients with acute myocardial infarction was present and the incidence of hospital mortality among patients with myocardial infarction was significantly higher than earlier. Significant difference was not found between various study periods neither for sex ratio, localization of myocardial infarction (anterior vs. inferior) nor in the ECG form of myocardial infarction (Q vs. Non-Q).