TRAUMATIC PULMONARY HERNIATION: A RARE CHEST TRAUMA MANIFESTATION.

Traumatic pulmonary hernia is an uncommon occurrence resulting from chest trauma, typically covered by the skin. Chest trauma may arise from penetrating or blunt mechanisms, with blunt trauma being more frequently observed. When lung herniation transpires, various symptoms such as chest pain, dyspnea, subcutaneous emphysema, bone crepitation, and hemoptysis (in cases of lung parenchymal damage) may manifest. We present the case of a 66-year-old woman suffering from chest pain and dyspnea after blunt chest trauma due to a fall induced by delirium following alcohol abuse.

[Early detection by urinary proteome analysis : A new concept in patient management of diabetic nephropathy]. / Früherkennung mittels Urinproteomanalyse : Ein neues Konzept im Patientenmanagement der diabetischen Nephropathie.

BACKGROUND: The early detection and treatment of diabetic nephropathy (DN) is of crucial importance as patients with diabetes mellitus represent the largest proportion of patients on dialysis, with the highest morbidity and mortality. Currently, the first clinical sign of incipient DN is microalbuminuria, but its precision is not optimal. Many studies now report that proteins and peptides are new biomarkers in urine that primarily depict the pathophysiology of DN and thus allow for improved diagnosis of DN. OBJECTIVES: The presentation of new concepts for the early detection and treatment of DN for better patient management. MATERIAL AND METHODS: A systematic literature search was carried out. RESULTS: Many potential markers have been described in the search for new biomarkers to diagnose DN by urinary proteome analysis. However, many of these studies were not meaningful due to the small number of samples. This limitation led to inadequate validation of proteins that could not be confirmed as markers. However, the diagnostic benefit of CKD 273, a multimarker of 273 protein fragments, was sustainably demonstrated for the early diagnosis of DN. This multi-marker shows significant advantages in the precision of diagnosis and prognosis compared to albuminuria. Furthermore, many of its peptide markers map the molecular pathophysiology of DN. CONCLUSIONS: Clinical urinary proteome analysis shows great benefits and is already an appropriate tool for the early detection of incipient DN.

[Troponins as biomarkers for myocardial injury and myocardial infarction]. / Troponine als Biomarker bei Myokardschaden und Myokardinfarkt.

Elevation of cardiac troponins above the 99th percentile of a healthy reference population is established as a marker for myocardial cell damage and is crucial for the diagnosis of myocardial infarction. In addition, corresponding clinical evidence of acute myocardial ischemia i.e. symptoms, changes in the electrocardiogram (ECG), wall motion abnormalities or suggestive angiographic findings are required for the diagnosis of myocardial infarction. Using modern highly sensitive assays myocardial infarction can be detected more frequently and earlier. On the other hand myocardial infarction can be ruled out with a higher diagnostic accuracy. Cardiac troponins are specific for myocardial cell damage but not for myocardial infarction and can be elevated in numerous other disease states. In these cases myocardial injury can be diagnosed independently of myocardial ischemia. Typical dynamics with rise and fall of troponin levels can distinguish acute myocardial injury (e. g. pericarditis/myocarditis and pulmonary embolism) from chronic myocardial injury (e. g. cardiomyopathy). Clinically, highly sensitive troponin assays are currently recommended in addition to the 0/3 h and 0/1 h algorithms for rapid inclusion or exclusion of myocardial infarction.

[Acute coronary syndrome with ST-elevation]. / Akutes Koronarsyndrom mit ST­Strecken-Hebung.

The current guidelines of the European Society of Cardiology have up-dated and confirmed the role of a primary percutaneous coronary intervention (PCI) as the preferred reperfusion therapy in patients with acute coronary syndrome and ST-elevation. The establishment of regional network structures for implementation of this reperfusion strategy is recommended and described. Primary PCI should preferably be carried out via the transradial route and should include the implantation of modern drug-eluting stents. In most cases of coronary multivessel disease, primary PCI should be limited to the treatment of the infarcted artery. Routine mechanical thrombus aspiration during primary PCI is no longer recommended. Recommendations for a specific anti-thrombotic and secondary prophylactic medication after primary PCI are highlighted.

[Acute coronary syndrome without ST-elevation (NSTE-ACS)]. / Akutes Koronarsyndrom ohne ST-Hebung (NSTE-ACS).

The timing of an invasive diagnosis and treatment strategy in patients with an acute coronary syndrome without ST-elevation (NSTE-ACS) depends on the patient's risk profile. In addition to the clinical symptoms, ST/T alterations in the resting ECG as well as an increase and kinetics of troponin are of crucial importance in this setting. For the majority of patients the highly sensitive troponin enables a rapid rule in or rule out strategy of a non-ST-segment elevation myocardial infarction (NSTEMI) with a 0/3 h algorithm. An even faster 0/1 h algorithm is increasingly being used; however, troponin only helps to identify patients with NSTEMI. Troponin-negative patients can still suffer from unstable angina pectoris. A dual antiplatelet therapy (DAPT) with acetylsalicylic acid (ASS) and an ADP receptor antagonist should be initiated in the acute phase and continued for 12 months, irrespective of the initial treatment strategy, e.g. percutaneous coronary intervention (PCI), bypass surgery or conservative treatment. In patients with a high bleeding risk a duration of 6 months only may be considered, whereas in patients with a high risk of ischemia the DAPT might be prolonged for up to 36 months.

[Severe Hemorrhagic Shock in a 93-Year Old Patient due to a Diagnostic Thoracocentesis]. / Schwerer hämorrhagischer Schock bei einem 93-jährigen Patienten nach diagnostischer Pleurapunktion.

An intercostal artery laceration is a rare iatrogenic complication following thoracocentesis and concerns especially elderly patients. We report a case of a severe hemorrhagic shock in a 93-year old patient due to diagnostic thoracocentesis.

Homocysteine concentration in coronary artery disease: Influence of three common single nucleotide polymorphisms.

BACKGROUND AND AIMS: Whether single nucleotide polymorphisms (SNPs) of homocysteine metabolism enzymes influence the rate of cardiovascular (CV) events in coronary artery disease (CAD) patients remains controversial. METHODS AND RESULTS: In this analysis, 1126 subjects from the AtheroGene study with CAD and 332 control subjects without known CAD were included. The following SNPs were investigated: methylentetrahydrofolate reductase (MTHFR-C667T), methionin synthetase (MS-D919G), and cystathionin beta synthetase (CBS-I278T). The endpoint was the combination of cardiovascular death, stroke, and non-fatal myocardial infarction (N = 286). The median follow-up time was 6.4 years. Kaplan-Meier curve analysis showed an increasing event rate with rising homocysteine levels (p < 0.001) in CAD patients. Further, in Cox-Regression analysis homocysteine was a predictor of the endpoint with a hazard ratio (HR) of 6.5 (95% CI: 2.9-14.6, p < 0.001) in the adjusted model including cardiovascular risk factors. Of the three SNPs, homozygous MTHFR SNP increased homocysteine levels significantly in patients with CAD and individuals without CAD (both p < 0.001). The SNPs in MS and CBS were not related to relevant changes in homocysteine levels in CAD patients or controls. The different SNPs of MTHFR, MS, and CBS were not related to an increased event rate. CONCLUSION: Homocysteine level is a strong predictor of CV events. Subjects with and without CAD and SNPs in the enzyme MTHFR had increased homocysteine levels. This was not observed for MS and CBS SNPs. Although MTHFR SNPs alter homocysteine levels in patients and controls, these polymorphisms had no impact on prognosis in CAD patients.

[Prognosis and therapy of inflammatory rheumatic diseases : Impact of renal manifestations]. / Prognose und Therapie von entzündlich-rheumatischen Erkrankungen : Einfluss der Nierenbeteiligung.

BACKGROUND: Inflammatory rheumatic diseases and their treatment cause various renal manifestations requiring modification of treatment. OBJECTIVES: Discussion of renal manifestations in selected rheumatic diseases, including their impact on general prognosis and therapy. MATERIALS AND METHODS: Basic literature and expert opinions are analyzed and discussed. RESULTS: Inflammatory rheumatic diseases and their treatment cause various renal manifestations, including glomerular, tubular, interstitial, and vascular damage. The type of damage determines both, associated clinical symptoms (i.e. hematuria, proteinuria, loss of kidney function) and the renal and overall survival as will be discussed here for rheumatoid arthritis, systemic lupus erythematosus, scleroderma, Sjögrens syndrome, cryoglobulinemia and ANCA-associated vasculitis. CONCLUSION: Renal manifestations are generally indicators of high disease activity and usually require more intensive treatment of the underlying rheumatic disease. Early and rigorous treatment, which has to be adapted to renal function, is capable of improving renal and overall survival in many of the affected patients.

[Results of preclinically placed thoracic drainages]. / Outcome-Analyse präklinisch gelegter Thoraxdränagen.

BACKGROUND: Thorax injuries are to be found in approximately 78 % amongst all victims of accidents. Moreover they implicate an increase in mortality rate. Consequently an adequate contemporary treatment has to begin preclinically, even if the conditions are less comfortable than in a clinical setting. Emergency doctors need to be familiar with the placement of chest tubes. METHODS: From 01.01.2007 to 31.12.2010 emergency doctors of the rescue helicopter site Christoph 20 had to place chest tubes directly at the scene of an accident in 49 patients. These patients were now reidentified and their clinical course reevaluated. By means of apparative diagnostics it was possible to analyse the location of the tips of the tubes. A comparison of the patient outcome versus the quality of preclinical thoracic drainage could be made. RESULTS: The preclinical placement of a chest tube became necessary mainly because of a blunt thoracic trauma. This was predominantly related to victims of traffic accidents, whereas male victims clearly dominated. 42 of those patients received further treatment at the Klinikum Bayreuth, enabling an analysis of the tube locations by CT scans. Six patients had been drained on both sides, contributing to the 48 tube tips that could be examined concerning their location. Of the 48 chest tubes 46 had been placed from a lateral approach. The ventral access according to Monaldi had only been chosen in two cases. Altogether nine incorrect placements, mainly within the right interlobe gap, were detected. CONCLUSION: The study collective showed a significant preference to the lateral approach when placing a chest tube at the emergency scene of an accident. In total a prevalence of 19 % incorrect placements could be revealed, meaning the chest tube had either been placed within the lung parenchyma, the interlobe gap or extrathoracically. Concerning the patient outcome no statistically significant difference regarding the clinical course after incorrect chest tube placement could be identified. The omission of an indicated preclinical thoracic drainge is certainly a more serious error than its incorrect placement with more serious consequences.

Ruptured pulmonary artery aneurysm mimicking pulmonary embolism.

Aneurysms of the pulmonary artery are very rare pathological vascular conditions. Peripheral pulmonary aneurysms have been reported only in a few cases. The causes of these aneurysms include extensive degenerative changes, traumas, infection and congenital malformations. Because of the imminent danger of rupture, surgical treatment should always be preferred. The following case report demonstrates one of a multitude of possible misdiagnoses for rupture of a pulmonary aneurysm.

["Atypical" anemia in a geriatric patient]. / "Unklare" Anämie bei einer hochbetagten Patientin.

A gastroenterologic examination was performed on an 83-year-old woman due to unexplained anemia; however, no bleeding site could be identified. Because of the advanced age of the patient, no further diagnostic efforts were made and iron-deficiency anemia was suspected. After 3 weeks, an emergency laparotomy was performed for acute diffuse peritonitis, which was diagnosed as perforation of the jejunum by a wooden foreign body. After extraction of the foreign body and closure of the perforation in the small intestine, healing proceeded without complications.

Polymorphisms of the tumor necrosis factor-alpha (TNF) and the TNF-alpha converting enzyme (TACE/ADAM17) genes in relation to cardiovascular mortality: the AtheroGene study.

Tumor necrosis factor (TNF) is a major cytokine involved in inflammatory reaction and a mortality predictor in patients with coronary artery disease (CAD). Plasma levels of soluble TNF (sTNF) depend on the rate of its synthesis but also on its shedding from cell surface, a mechanism mainly regulated by the TNF alpha converting enzyme (TACE or ADAM17). We investigated the relationship between ADAM17 and TNF polymorphisms, circulating levels of shed ADAM17 substrates (sTNF, sTNFR1 and sTNFR2), and cardiovascular risk in a prospective cohort of CAD patients. Five tag single-nucleotide polymorphisms (SNPs) of the ADAM17 gene as well as four previously described TNF SNPs were genotyped in the Atherogene Study composed of 1,400 CAD patients among which 136 died from a cardiovascular (CV) cause. sTNF, sTNFR1, and sTNFR2 concentrations were all significantly elevated in patients with future CV death, independently of other clinical/biological variables. While none of the studied TNF SNPs was associated with sTNF, sTNFR1, nor sTNFR2 levels, the ADAM17 -154A allele was found associated with a 14% increase of sTNF levels as compared to the -154C allele (p = 0.0066). Moreover, individuals carrying the 747Leu allele displayed a borderline increased risk of future cardiovascular death [odds ratio, 2.06 (1.05-4.04), p = 0.03]. These results suggest a role of ADAM17 in the regulation of sTNF plasma levels and identifies ADAM17 gene as a candidate for CAD. Tumor necrosis factor (TNF) is a major cytokine involved in inflammatory reaction and a mortality predictor in patients with coronary artery disease (CAD). We have studied the association of ADAM17 and TNF polymorphisms with circulating levels of shed ADAM17 substrates (sTNF, sTNFR1 and sTNFR2) and with cardiovascular risk in a large population of individuals with CAD (Atherogene Study, n = 1,400). Two newly identified polymorphisms, obtained by a systematic sequencing of the ADAM17 gene, C-154A and Ser747leu, slightly influence respectively sTNF plasma levels and the risk of cardiovascular death.

[Severe thoracic bleeding - 25 years after nephrectomy]. / Massive thorakale Blutung ­ 25 Jahre nach Nephrektomie.

We report a case of a 62 year old patient, who was hospitalised due to haemorrhagic shock. The cause was a rupture of the pulmonary artery due to metastasis of a renal cell carcinoma. This cause is now reported for the first time. The primary tumour (pT2,pN0,M0,R0) was resected 25 years ago. This case demonstrates that after curative nephrectomy pulmonary metastasis can occur, even after decades. This is why patients of this type need lifelong follow-up.

Prognostic value of plasma tissue factor and tissue factor pathway inhibitor for cardiovascular death in patients with coronary artery disease: the AtheroGene study.

BACKGROUND: Tissue factor (TF) and its specific inhibitor, tissue factor pathway inhibitor (TFPI), are important contributors to the initiation of the coagulation process. OBJECTIVES: To compare plasma levels of soluble TF (sTF) and free-TFPI (f-TFPI) between patients with stable angina pectoris (SAP) and acute coronary syndrome (ACS) and to assess the impact of the two variables on long-term prognosis. PATIENTS/METHODS: Patients with SAPs (n = 1146) and acute coronary syndrome (n = 523) from the AtheroGene study were included and followed for 2.3 years. Because of the strong impact of unfractionated heparin (UFH) on f-TFPI levels, but not on sTF levels, patients having received UFH before blood drawing were excluded from the analyses on f-TFPI (n = 226). RESULTS: On admission, no significant differences in sTF levels were observed between SAP and ACS patients. By comparison to patients with stable angina, f-TFPI levels significantly increased in patients with acute unstable angina and further increased in patients presenting with non-ST-elevation myocardial infarction and ST-elevation myocardial infarction (P < 10(-4)). Among the 1669 individuals with a coronary artery disease, 56 died from a cardiovascular cause. In prospective analyses, high sTF levels were independently associated with an increased risk of cardiovascular death in individuals with ACS (fully adjusted hazard ratio associated with one quartile increase = 2.06; 95% confidence interval 1.24-3.45; P = 0.006) but not in those with SAP (hazard ratio = 1.07; 95% confidence interval 0.78-1.46; P = 0.67). In SAP and ACS patients, high f-TFPI levels were not independently associated with an increased risk of cardiovascular death. CONCLUSIONS: Plasma sTF levels were predictive of cardiovascular mortality in individuals with ACS, whereas f-TFPI levels were associated with the severity of myocardial damage on admission but were not independently related to outcome.

DNA recognition by splicing variants of the Wilms' tumor suppressor, WT1.

The Wilms' tumor suppressor, WT1, is a zinc finger transcriptional regulator which exists as multiple forms owing to alternative mRNA splicing. The most abundant splicing variants contain a nine-nucleotide insertion encoding lysine, threonine, and serine (KTS) in the H-C link region between the third and fourth WT1 zinc fingers which disrupts binding to a previously defined WT1-EGR1 binding site. We have identified WT1[+KTS] binding sites in the insulin-like growth factor II gene and show that WT1[+KTS] represses transcription from the insulin-like growth factor II P3 promoter. The highest affinity WT1[+KTS] DNA binding sites included nucleotide contacts involving all four WT1 zinc fingers. We also found that different subsets of three WT1 zinc fingers could bind to distinct DNA recognition elements. A tumor-associated, WT1 finger 3 deletion mutant was shown to bind to juxtaposed nucleotide triplets for the remaining zinc fingers 1, 2, and 4. The characterization of novel WT1 DNA recognition elements adds a new level of complexity to the potential gene regulatory activity of WT1. The results also present the possibility that altered DNA recognition by the dominant WT1 zinc finger 3 deletion mutant may contribute to tumorigenesis.

Haemostatic factors and the risk of cardiovascular death in patients with coronary artery disease: the AtheroGene study.

OBJECTIVE: To get a better insight into the role of hemostasis in coronary artery disease (CAD), we assessed the impact of von Willebrand factor (vWF), fibrinogen, thrombin-antithrombin (TAT) complexes, D-dimers, and plasmin-antiplasmin (PAP) complexes on the risk of cardiovascular event in a prospective cohort of CAD patients. METHODS AND RESULTS: The prospective Atherogene cohort includes 1057 individuals with an angiographically proven coronary artery disease at baseline. After a median follow-up of 6.6 years, 135 individuals died from a cardiovascular cause and 97 had a nonfatal cardiovascular event. Higher levels of all 5 hemostatic markers at baseline were associated with an increased risk of cardiovascular death, but not of nonfatal event. Except for vWF, these associations remained significant after adjustment for conventional cardiovascular risk factors and C-reactive protein (CRP) levels (P for trend according to increasing tertiles=0.20, 0.011, 0.026, 0.019, and 0.01 for vWF, fibrinogen, TAT, D-Dimer, and PAP, respectively). When including the 5 hemostatic markers in a stepwise Cox regression analysis where conventional risk factors and CRP were forced into the model, fibrinogen and D-dimers remained independently associated with the risk of cardiovascular death. Adjusted hazard ratios (95% CI) associated with one SD increase of fibrinogen and D-dimers were 1.27 (1.04 to 1.55) and 1.29 (1.09 to 1.53), respectively. CONCLUSIONS: In patients with coronary artery disease, fibrinogen and D-dimer levels are independent predictors of subsequent cardiovascular death. Our data support a role of impaired coagulation/fibrinolysis process in the complications of coronary artery disease.

Long-term cost-effectiveness of clopidogrel in patients with acute coronary syndrome without ST-segment elevation in Germany.

Patients with acute coronary syndrome without ST-segment elevation receiving clopidogrel in addition to acetylsalicylic acid (ASA) showed a 20% risk reduction in comparison to patients receiving ASA monotherapy (CURE trial). Economic models for assessing the impact on costs exist for several countries but not for Germany on a long-term basis. The objective of this model adaptation is to assess the long-term economic impact of clopidogrel taken in addition to ASA in Germany. A Markov model with six states [at risk, first year with stroke, following years with stroke, first year with new myocardial infarction (MI), following years with MI, and death] was adapted for Germany. Model outcome was life-years saved. Effects of 1-year treatment were calculated based on the CURE trial. Resource use for the different health states was based on published data, which included costs for drugs, outpatient care, hospitalization, rehabilitation and nursing. Risk data for MI and stroke were based on Swedish data and validated for the German adaptation. The model calculates lifetime costs and survival length. Costs were estimated from the payers' perspective. A series of one-way sensitivity analyses was conducted (follow-up costs, discount rates). The Markov analysis predicts a survival of 8.89years in the placebo treatment group and 9.02 years in the clopidogrel treatment group. The cumulated costs were euro 8,548 and euro 8,953, respectively. The incremental cost-effectiveness ratio (ICER) was euro 3,113 for each life-year saved. The model was robust regarding variations in key parameters in the sensitivity analysis, resulting in a range of ICER from euro 1,338 to euro 9,322. Our results are in line with the results for other healthcare systems. Adding clopidogrel to ASA for patients with acute coronary syndrome without ST-segment elevation generated an additional life-year saved at a comparably low value of euro 3,113. One-year treatment with clopidogrel is a cost-effective treatment option in patients with acute coronary syndrome from the perspective of a third-party payer in Germany.

The predictive value of different equations for estimation of glomerular filtration rate in patients with coronary artery disease - Results from the AtheroGene study.

BACKGROUND: Impaired renal function leads to dramatically increased risk for the development and progression of coronary artery disease (CAD). Therefore we aimed to assess the predictive value of different equations for estimated glomerular filtration rate (eGFR) in CAD-patients. METHODS: From the AtheroGene study 2135 patients were included. eGFR was calculated using the 4-variable Modification of Diet in Renal Disease (4MDRD) equation for serum creatinine (sCr), the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for sCr and cystatin C (CysC) each alone, and in combination (CysC/sCr). eGFR was assessed regarding the combined outcome of cardiovascular death and non-fatal myocardial infarction and regarding complex CAD represented by a SYNTAX score ≥23. Median follow-up was 4.3years. RESULTS: Only the CKD-EPI equation using CysC could differentiate between eGFR >90ml/min/1.73m(2) vs. eGFR 60-90ml/min/1.73m(2) according to the occurrence of an endpoint event (log-rank test p=0.009). In the Cox regression analysis only eGFR calculated by CKD-EPI equation for CysC (Hazard ratio per 1 standard deviation (HR) 1.27 (95% CI 1.07-1.50); p=0.007) and for CysC/sCr (HR 1.22 (95% CI 1.02-1.46); p=0.026) were predictive regarding the outcome after adjustment for cardiovascular risk factors and Nt-proBNP. Furthermore, only eGFR calculated by CKD-EPI equation for CysC (odds ratio (OR) 1.57 (95% CI 1.36-1.78); p<0.001) and for CysC/sCr (OR 1.32 (95% CI 1.13-1.53); p<0.001) were significantly associated with a SYNTAX score ≥23. CONCLUSION: In patients with CAD the CKD-EPI equation for CysC and for CysC/sCr provided the best predictive value regarding the prognosis and the severity of CAD.

Double-blind study of the safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting : the clopidogrel aspirin stent international cooperative study (CLASSICS).

BACKGROUND: Combination therapy with the ADP receptor antagonist ticlopidine plus aspirin has emerged as standard care after coronary stenting. Clopidogrel, a new ADP receptor antagonist, has greater molar potency than ticlopidine and better safety/tolerability. METHODS AND RESULTS: Patients (n=1020) were randomized after successful stent placement and initiated on a 28-day regimen of either (1) 300-mg clopidogrel loading dose and 325 mg/d aspirin on day 1, followed by 75 mg/d clopidogrel and 325 mg/d aspirin; (2) 75 mg/d clopidogrel and 325 mg/d aspirin; or (3) 250 mg BID ticlopidine and 325 mg/d aspirin. The primary end point consisted of major peripheral or bleeding complications, neutropenia, thrombocytopenia, or early discontinuation of study drug as the result of a noncardiac adverse event during the study-drug treatment period. The primary end point occurred in 9.1% of patients (n=31) in the ticlopidine group and 4.6% of patients (n=31) in the combined clopidogrel group (relative risk 0.50; 95% CI 0.31 to 0.81; P=0.005). Overall rates of major adverse cardiac events (cardiac death, myocardial infarction, target lesion revascularization) were low and comparable between treatment groups (0.9% with ticlopidine, 1.5% with 75 mg/d clopidogrel, 1.2% with the clopidogrel loading dose; P=NS for all comparisons). CONCLUSIONS: The safety/tolerability of clopidogrel (plus aspirin) is superior to that of ticlopidine (plus aspirin) (P=0.005). The 300-mg loading dose was well tolerated, notably with no increased risk of bleeding. Secondary end point data are consistent with the hypothesis that clopidogrel and ticlopidine have comparable efficacy with regard to cardiac events after successful stenting.