Antwort auf den Leserbrief von Valhaus et al. Zu unserer Kasuistik „Kardiogener Schock 4 Stunden nach akut-PTCA bei Hinterwandinfarkt“

Ohne Zusammenfassung     

The pathophysiology of chronic subdural hematoma revisited: emphasis on aging processes as key factor

GeroScience - Chronic subdural hematoma (CSH) affects mostly elderly subjects. Previously, pathophysiological concepts suggested that CSH is secondary to degradation of subdural collections of...     

Too little aspirin for secondary prevention after acute myocardial infarction in patients at high risk for cardiovascular events: Results from the MITRA study

Background

A meta-analysis of randomized trials has shown a significant reduction of mortality rate in patients receiving aspirin for secondary prevention after acute myocardial infarction (AMI). However, a significant number of patients do not receive aspirin after AMI. Little is known about why aspirin is withheld or the long-term outcome of these patients today.

Methods

The Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) registry is a multicenter registry of patients with AMI in Germany.

Results

Of 4902 patients, 509 (10%) did not receive aspirin at the time of discharge from the hospital. The mean follow-up period for these patients was 17 months. Relative contraindications to aspirin were significantly associated with the withholding of aspirin (in-hospital bleeding: odds ratio [OR], 3.56; 95% CI, 1.86-6.80; history of peptic ulcer: OR, 2.49; 95% CI, 1.62-3.83). Absolute contraindications to aspirin were rare (2.2%). Other medications of proven benefit were also given less often in these patients (β-blockers: 49.0% vs 61.9%, P <.001; angiotensin-converting enzyme inhibitors: 65.6% vs 70.2%, P = .06; statins: 12.2% vs 15.1%, P = .10). Patients who were not given aspirin were at high risk for vascular events. They were more likely to have a history of prior AMI (OR, 1.34; 95% CI, 1.02-1.79), were in critical clinical condition at admission more often (cardiogenic shock: OR, 1.98; 95% CI, 1.09-3.56; overt heart failure: OR, 1.6; 95% CI, 1.05-2.3), and received acute revascularization less often (OR, 1.32; 95% CI, 1.05-1.67). The 1-year mortality was 2-times higher in patients who did not receive aspirin than in patients who did receive aspirin (16.5% vs 8.3%, P <.001). A significant association of withheld aspirin at discharge with a higher long-term mortality rate was confirmed with multivariate analysis (OR, 1.62; 95% CI, 1.15-2.29).

Conclusions

Ten percent of patients who sustained an AMI did not receive aspirin at the time of hospital discharge. Most of these patients were at high risk for cardiovascular events. Withheld aspirin was significantly associated with higher mortality rate during follow up.     

The mouse Pax21Neu mutation is identical to a human PAX2 mutation in a family with renal-coloboma syndrome and results in developmental defects of the brain, ear, eye, and kidney

We describe a new mouse frameshift mutation (Pax2^1Neu) with a 1-bp insertion in the Pax2 gene. This mutation is identical to a previously described mutation in a human family with renal-coloboma syndrome [Sanyanusin, P., McNoe, L. A., Sullivan, M. J., Weaver, R. G. & Eccles, M. R. (1995) Hum. Mol. Genet. 4, 2183–2184]. Heterozygous mutant mice exhibit defects in the kidney, the optic nerve, and retinal layer of the eye, and in homozygous mutant embryos, development of the optic nerve, metanephric kidney, and ventral regions of the inner ear is severely affected. In addition, we observe a deletion of the cerebellum and the posterior mesencephalon in homozygous mutant embryos demonstrating that, in contrast to mutations in Pax5, which is also expressed early in the mid-hindbrain region, loss of Pax2 gene function alone results in the early loss of the mid-hindbrain region. The mid-hindbrain phenotype is similar to Wnt1 and En1 mutant phenotypes, suggesting the conservation of gene regulatory networks between vertebrates and Drosophila.     

A‐Fibers Mediate Cold Hyperalgesia in Patients with Oxaliplatin‐Induced Neuropathy

Cold hyperalgesia is a common side effect of oxaliplatin treatment; still, the pathophysiological and molecular mechanisms as well as the contribution of different primary afferent fiber systems are unclear. Therefore, patients with oxaliplatin‐induced acute neuropathy with (n = 6) and without (n = 7) cold hyperalgesia were tested by applying a preferential blockade of peripheral myelinated A‐fiber afferents in combination with quantitative sensory testing. Additionally, an interview‐based questionnaire assessed the severity of symptoms and the impact on daily activities. Results indicate a deficit of cold perception in patients without cold hyperalgesia compared to patients with cold hyperalgesia prior to A‐fiber blockade. In patients with cold hyperalgesia, a preferential blockade of A‐fibers abolished cold hyperalgesia. This suggests that oxaliplatin‐induced cold hyperalgesia is mediated by A‐fibers and that a deficit in A‐fiber function might prevent the development of cold hyperalgesia. The work supports findings in rodents and in human sural nerve biopsies indicating that oxaliplatin interferes with axonal ion conductance in intact A‐fibers by sensitizing potassium and/or sodium channels. Drugs that act on these molecular targets might be of potential value to treat oxaliplatin‐induced cold hyperalgesia.     

High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a Murine Model of Extraosseous Calcification

Cardiovascular calcification is prevalent in the aging population and in patients with chronic kidney disease (CKD) and diabetes mellitus, giving rise to substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP) is an important inhibitor of calcification. The aim of this study was to evaluate the impact of high-dose menaquinone-7 (MK-7) supplementation (100 µg/g diet) on the development of extraosseous calcification in a murine model. Calcification was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham operated animals served as controls. Animals received high or low MK-7 diets for 12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance, and cardiac function. CKD provoked increased aortic (1.3 fold; p < 0.05) and myocardial (2.4 fold; p < 0.05) calcification in line with increased alkaline phosphatase levels (2.2 fold; p < 0.01). MK-7 supplementation inhibited cardiovascular calcification and decreased aortic alkaline phosphatase tissue concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger ribonucleic acid (mRNA) expression (10-fold; p < 0.05). CKD-induced arterial hypertension with secondary myocardial hypertrophy and increased elastic fiber breaking points in the arterial tunica media did not change with MK-7 supplementation. Our results show that high-dose MK-7 supplementation inhibits the development of cardiovascular calcification. The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures.