Dexamethasone-related adrenal insufficiency in patients with brain and skull base tumours.

PURPOSE: This study aimed to evaluate the prevalence of glucocorticoid-induced adrenal insufficiency in a cohort of patients with brain and skull base tumours and to identify factors which may predict its occurrence. METHODS: Patients with brain or skull base tumours attending for a short synacthen test (SST) (adrenocorticotropin hormone (ACTH) stimulation test) at a single institution over a 3-year period were retrospectively identified. Baseline demographics and dexamethasone exposure were examined. Only patients with dexamethasone exposure were included in the final analysis looking at the primary end point of SST failure. Fisher's exact test, Student's t test, Mann-Whitney test and the Kendall's tau-b test were used to evaluate the influence of age, gender, diagnosis and mean pituitary radiation dose on the primary endpoint. Receiver operating characteristic (ROC) curves were generated to explore the impact of duration and total exposure to dexamethasone on likelihood of SST failure. RESULTS: Thirty-one of 51 patients with previous dexamethasone exposure failed their first SST (61%). No significant relationship was demonstrated between age, gender, diagnosis or mean pituitary radiation dose and SST failure. Duration of and total exposure to dexamethasone were significantly associated with SST failure (p = 0.001 and p = 0.007, respectively). ROC curves generated values of 78 days and 171 mg days to give a sensitivity of 94 and 97%, respectively, to detect SST failure. CONCLUSIONS: Duration of dexamethasone use and total exposure predict for adrenal insufficiency in patients with brain and skull base tumours. Values derived from this study may be useful to identify patients at higher risk of adrenal suppression who require empirical hydrocortisone pending formal testing of the hypothalamic-pituitary-adrenal axis.

Study of GeSn based heterostructures: towards optimized group IV MQW LEDs.

We present results on CVD growth and electro-optical characterization of Ge(0.92)Sn(0.08)/Ge p-i-n heterostructure diodes. The suitability of Ge as barriers for direct bandgap GeSn active layers in different LED geometries, such as double heterostructures and multi quantum wells is discussed based on electroluminescence data. Theoretical calculations by effective mass and 6 band k∙p method reveal low barrier heights for this specific structure. Best configurations offer only a maximum barrier height for electrons of about 40 meV at the Γ point at room temperature (e.g. 300 K), evidently insufficient for proper light emitting devices. An alternative solution using SiGeSn as barrier material is introduced, which provides appropriate band alignment for both electrons and holes resulting in efficient confinement in direct bandgap GeSn wells. Finally, epitaxial growth of such a complete SiGeSn/GeSn/SiGeSn double heterostructure including doping is shown.

Drainless robot-assisted minimally invasive oesophagectomy-randomized controlled trial (RESPECT).

BACKGROUND: The purpose of this randomized trial is to evaluate the early removal of postoperative drains after robot-assisted minimally invasive oesophagectomy (RAMIE). Evidence is lacking about feasibility, associated pain, recovery, and morbidity. METHODS/DESIGN: This is a randomized controlled multicentric trial involving 72 patients undergoing RAMIE. Patients will be allocated into two groups. The "intervention" group consists of 36 patients. In this group, abdominal and chest drains are removed 3 h after the end of surgery in the absence of contraindications. The control group consists of 36 patients with conventional chest drain management. These drains are removed during the further postoperative course according to a standard algorithm. The primary objective is to investigate whether postoperative pain measured by NRS on the second postoperative day can be significantly reduced in the intervention group. Secondary endpoints are the intensity of pain during the first week, analgesic use, number of postoperative chest X-ray and CT scans, interventions, postoperative mobilization (steps per day as measured with an activity tracker), postoperative morbidity and mortality. DISCUSSION: Until now, there have been no trials investigating different intraoperative chest drain strategies in patients undergoing RAMIE for oesophageal cancer with regard to perioperative complications until discharge. Minimally invasive approaches combined with enhanced recovery after surgery (ERAS) protocols lower morbidity but still include the insertion of chest drains. Reduction and early removal have been proposed after pulmonary surgery but not after RAMIE. The study concept is based on our own experience and the promising current results of the RAMIE procedure. Therefore, the presented randomized controlled trial will provide statistical evidence of the effectiveness and feasibility of the "drainless" RAMIE. TRIAL REGISTRATION: ClinicalTrials.gov NCT05553795. Registered on 23 September 2022.

Expression of an ASCL2 related stem cell signature and IGF2 in colorectal cancer liver metastases with 11p15.5 gain.

BACKGROUND AND AIMS: Liver metastases are the leading cause of death in colorectal cancer. To gain better insight into the biology of metastasis and possibly identify new therapeutic targets we systematically investigated liver-metastasis-specific molecular aberrations. METHODS: Primary colorectal cancer (pCRC) and matched liver metastases (LMs) from the same patients were analysed by microarray-based comparative genomic hybridisation in 21 pairs and gene expression profiling in 18 pairs. Publicly available databases were used to confirm findings in independent datasets. RESULTS: Chromosome aberration patterns and expression profiles of pCRC and matched LMs were strikingly similar. Unsupervised cluster analysis of genomic data showed that 20/21 pairs were more similar to each other than to any other analysed tumour. A median of only 11 aberrations per patient was found to be different between pCRC and LM, and expression of only 16 genes was overall changed upon metastasis. One region on chromosome band 11p15.5 showed a characteristic gain in LMs in 6/21 patients. This gain could be confirmed in an independent dataset of LMs (n=50). Localised within this region, the growth factor IGF2 (p=0.003) and the intestinal stem cell specific transcription factor ASCL2 (p=0.029) were found to be over-expressed in affected LM. Several ASCL2 target genes were upregulated in this subgroup of LM, including the intestinal stem cell marker OLFM4 (p=0.013). The correlation between ASCL2 expression and four known direct transcriptional targets (LGR5, EPHB3, ETS2 and SOX9) could be confirmed in an independent expression dataset (n=50). CONCLUSIONS: With unprecedented resolution a striking conservation of genomic alterations was demonstrated in liver metastases, suggesting that metastasis typically occurs after the pCRC has fully matured. In addition, we characterised a subset of liver metastases with an ASCL2-related stem-cell signature likely to affect metastatic behaviour of tumour cells.

Effect of short-term intraocular pressure increase on cat retinal ganglion cell activity.

By means of microelectrode recordings receptive field properties and flicker responses of cat retinal ganglion cells were studied during elevated intraocular pressure (IOP). At moderate IOP elevation (perfusion pressure, PP, approx. 50 mm Hg), a slight increase in the maintained activity and the neuronal activation obtained from the receptive field (RF)-center or RF-periphery occurred in some of the neurons. At critical perfusion pressure (PP 30-10 mm Hg), the RF-periphery mechanisms were less sensitive to ischemia than the RF-center mechanisms. The spontaneous activity was completely suppressed at an average PP of 36.6 +/- 9.0 mm Hg, the flicker-evoked responses at 17.7 +/- 9.6 mm Hg. At critical perfusion pressures, the stimulus-response latency increased by 20 ms at stimulation frequencies of 10-20 Hz. The critical flicker frequency was already slightly reduced at a PP of 50 mm Hg and decreased further with a further decrease in PP. The threshold values of the intensity function shifted to higher luminance levels when PP was reduced to less than 40 mm Hg, but the slope remained constant. A close interneuronal correlation was found in simultaneous recordings of pairs of ganglion cells during different levels of increased IOP. This finding indicates that the interneuronal response variability to IOP increase appearing in successively recorded neurons was predominantly caused by experimental factors. The main impairment in retinal neuronal function during increased IOP seems to occur proximal to the receptors but distal to the retinal ganglion cell somata.

Effect of ethanol on stretch response of muscle receptors in cats.

The response of muscle spindles and tendon organs to steady and sinusoidal muscle stretch was investigated at different blood alcohol concentrations (BAC). After initial anesthesia (pentobarbital), cats were spinalized, the lumbar ventral roots cut and the gastrocnemius muscles of one hindleg prepared for controlled stretching. The animals were paralyzed and artificial respiration was applied. Action potentials from isolated Ia/Ib/II afferent fibers could be recorded. Under steady stretch conditions, all fibers responded to an increasing BAC with an increase in firing rate. This could be observed already at 0.8 mg/ml BAC. The increase in discharge rate reached at the most 80 imp/s. During intoxication the regularity of firing was higher than in the no-alcohol situation. At blood alcohol concentrations higher than 5 mg/ml, the neuronal activity suddenly dropped to zero, exhibiting an irregular impulse pattern. The increase in discharge rate at steady stretch is regarded to be of minor significance in the explanation of the impairment of motor performance under ethanol. When sinusoidal stretch was applied, the increase in the mean discharge rate was smaller than at steady stretch conditions. Up to about 10 mg/ml BAC the periodical modulation of firing rate during sinusoidal stretch of a large amplitude remained mainly unchanged. After the discharge rate had dropped to zero for the steady stretch condition at high BAC, elicitation of action potentials was always possible using dynamic stretch.