DNA flow-cytometric analysis in colorectal cancer: A comparison of metastasizing and non-metastasizing tumours

The most common cause of death in patients with colorectal cancer is metastatic liver disease. In order to identify patients at a high risk of developing hepatic secondaries from colorectal cancers, DNA content was measured in metastasizing colorectal primaries (Group I, n= 32) as well as in their subsequently resected liver secondaries and in sections of non-metastasizing colorectal cancers (Group II, n= 25). A modified interpretation system involving both a DNA index and percentage of cycling cells (those in S and G2 + M phases) was developed. DNA content was measured in paraffin-embedded sections by flow cytometry using internal controls (human peripheral blood mononuclear cells) and non-malignant tissue controls (19 patients with diverticular disease). In Group I there were significantly more tumours with both abnormal ploidy (aneuploid or abnormal tetraploid peak) and > 15% cycling cells compared with Group II (Chi-squared; P= 0.034). The combination of abnormal ploidy and > 15% cycling cells was superior to Dukes’ classification for identifying metastasizing tumours (Logistic Regression; P= 0.047). However, it was not possible to discriminate between the two groups using either DNA ploidy or the percentage of cycling cells alone. The metastasizing colorectal cancers exhibited similar DNA ploidy characteristics and had a similar percentage of cycling cells compared with their liver metastases. These results suggest that tumour DNA ploidy plus the percentage of cycling cells may predict the development of liver metastases and thus survival in patients with colorectal cancer.     

ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome

It was shown recently that mutations of the ATRX gene give rise to a severe, X-linked form of syndromal mental retardation associated with alpha thalassaemia (ATR-X syndrome). In this study, we have characterised the full-length cDNA and predicted structure of the ATRX protein. Comparative analysis shows that it is an entirely new member of the SNF2 subgroup of a superfamily of proteins with similar ATPase and helicase domains. ATRX probably acts as a regulator of gene expression. Definition of its genomic structure enabled us to identify four novel splicing defects by screening 52 affected individuals. Correlation between these and previously identified mutations with variations in the ATR-X phenotype provides insights into the pathophysiology of this disease and the normal role of the ATRX protein in vivo.      

The role of spreading depolarization in subarachnoid hemorrhage

Subarachnoid hemorrhage (SAH) is a devastating disease associated with death and poor functional outcome. Despite decades of intense research and improvements in clinical management, delayed cerebral ischaemia (DCI) remains the most important cause of morbidity and mortality after SAH. The key role of angiographic cerebral vasospasm, thought to be the main cause of DCI, has been questioned. Emerging evidence suggests that DCI is likely to have a multifactorial etiology. Over the last few years, spreading depolarization (SD) has been identified as a potential pathophysiological mechanism contributing to DCI. The presence of cortical spreading ischaemia, due to an inverse hemodynamic response to SD, offers a possible explanation for DCI and requires more intensive research. Understanding the role of SD as another mechanism inducing DCI and its relationship with other pathological factors could instigate the development of new approaches to the diagnosis and treatment of DCI in order to improve the clinical outcome.     

Prothrombin complex concentrate facilitates emergency spinal surgery in anticoagulated patients

Background

Oral anticoagulants are commonly used in the ageing population and therefore, spine surgeons are increasingly confronted with anticoagulated patients requiring surgical therapy. ‘Bridging therapies’ with heparins are established in elective settings, but the time frame for haemostasis restoration may be too long for patients presenting with acute spinal pathology and impending disability. The goal of this study was to analyse the feasibility of prothrombin complex concentrate (PCC) administration to facilitate emergency spinal surgery in anticoagulated patients.

Method

A retrospective analysis of the institutional database of neurosurgical patients receiving PCC from February 2007 to December 2013 (n?=?485) identified 18 patients who received PCC prior to emergency spinal surgery. Clinical characteristics, as well as modalities of PCC administration and parameters of haemostasis were analysed. Furthermore, haemorrhagic complications and thromboembolic events in the further course were evaluated.

Results

Spinal pathologies requiring urgent neurosurgical decompression were spinal haematoma (n?=?9), spinal metastasis (n?=?5), vertebral body fracture (n?=?2), and disc herniation (n?=?2). The mean international normalized ratio (INR) on admission was 2.27?±?1.20 and after administration of PCC (mean: 1,944?±?953 I.U.), INR significantly decreased to 1.12?±?0.10 (p?<?0.001). Emergency surgery was initiated within 4.4 h after PCC administration (range: 0–16.6 h). Postoperatively, symptoms improved in 12 patients (66.7 %). There were two deaths (11 %), one caused by acute myocardial infarction on the fourth postoperative day. Bleeding complications occurred in two patients (epidural haemorrhage n?=?1, rectal tumour haemorrhage n?=?1).

Conclusions

The administration of PCC facilitates emergency spinal surgery in anticoagulated patients who present with acute spinal pathology requiring urgent neurosurgical decompression. The risk of PCC-associated thromboembolic events seems to be low and justifies the use of PCC in order to avoid permanent disablement resulting from delayed surgery or non-operation.     

Standards of Scoring,Monitoring, and Parameter Targeting in German Neurocritical Care Units: A National Survey

Background

Optimal management of physiological parameters in neurological/neurosurgical intensive care units (NICUs) is largely unclear as high-quality evidence is lacking. The aim of this survey was to investigate if standards exist in the use of clinical scores, systemic and cerebral monitoring and the targeting of physiology values and in what way this affects clinical management in German NICUs.

Methods

National survey, on-line anonymized questionnaire. German departments stating to run a neurological, neurosurgical or interdisciplinary neurological/neurosurgical intensive care unit were identified by a web-based search of all German hospitals and contacted via email.

Results

Responses from 78 German NICUs were obtained. Of 19 proposed clinical/laboratory/radiological scores only 5 were used regularly by >60 %. Bedside neuromonitoring (NM) predominantly consisted of transcranial Doppler sonography (94 %), electroencephalography (92 %) and measurement of intracranial pressure (ICP) (90 %), and was installed if patients had or were threatened by elevated ICP (86 %), had specific diseases like subarachnoid hemorrhage (51 %) or were comatose (35 %). Although mean trigger values for interventions complied with guidelines or wide-spread customs, individual trigger values varied widely, e.g., for hyperglycemia (maximum blood glucose between 120 and 250 mg/dl) or for anemia (minimum hemoglobin values between 5 and 10 g/dl).

Conclusions

Although apparently aiming for standardization in neurocritical care, German NICUs show substantial differences in NM and monitoring-associated interventions. In terms of scoring and monitoring methods, German NICUs seem to be quite conservative. These survey results suggest a need of prospective and randomized interventional trials in neurocritical care to help define standards and target values.     

Interventionelle Therapieverfahren bei akuter nekrotisierender Pankreatitis

The clinical course of acute pancreatitis is variable. Severe pancreatitis is observed in up to 20% of cases and is associated with high mortality rates of up to 40%. The most serious complication is the infection of the (peri-)pancreatic necroses. The therapeutic goal is debridement of the infected material. Whereas surgical methods still represent the gold standard, minimally invasive interventional approaches are gaining importance. This article reviews the different interventional procedures, particularly percutaneous, CT-guided drainage and necrosectomy. Furthermore, an overview of published studies about interventional therapy in patients with acute necrotizing pancreatitis is given.     

Influence of norepinephrine and dopamine on cortical perfusion,EEG activity,extracellular glutamate,and brain edema in rats after controlled cortical impact injury

Following traumatic brain injury, catecholamines given to ameliorate cerebral perfusion may induce brain damage via cerebral arteriolar constriction and increased neuronal excitation. In the present study the acute effects of norepinephrine and dopamine on pericontusional cortical perfusion (rCBF), electroencephalographic (EEG) activity, extracellular glutamate, and brain edema were investigated in rats following controlled cortical impact injury (CCI). rCBF, cerebral perfusion pressure (CPP), EEG activity, and glutamate were determined before, during, and after infusing norepinephrine or dopamine, increasing MABP to 120 mm Hg for 90 min at 4 h after CCI. Control rats received physiological saline. At 8 h after CCI, hemispheric swelling and water content were determined gravimetrically. Following CCI, rCBF was significantly decreased. In parallel to elevating MABP and CPP, rCBF was significantly increased by norepinephrine and dopamine, being mostly pronounced with norepinephrine (+44% vs. +29%). In controls, rCBF remained diminished (-45%). EEG activity was significantly increased by norepinephrine and dopamine, while pericontusional glutamate was only elevated by norepinephrine (28 +/- 6 vs. 8 +/- 4 microM). Brain edema was not increased compared to control rats. Despite significantly increasing MABP and CPP to the same extent, norepinephrine and dopamine seem to differentially influence pericontusional cortical perfusion and glutamatergic transmission. In addition to the pressure-passive increase in CPP local cerebral effects seem to account for the sustained norepinephrine-induced increase in pericontusional cortical perfusion. The significantly elevated pericontusional glutamate concentrations in conjunction with the increased EEG activity suggest a sustained metabolically driven increase in cortical perfusion during norepinephrine infusion.