MMP3 activity rather than cortical stiffness determines NHE1-dependent invasiveness of melanoma cells.

BACKGROUND: Both cell adhesion and matrix metalloproteinase (MMP) activity depend on pH at the cell surface. By regulating extracellular juxtamembrane pH, the Na+/H+ exchanger NHE1 plays a significant part in human melanoma (MV3) cell migration and invasion. Because NHE1, besides its pH-regulatory transport function, also serves as a structural element tying the cortical actin cytoskeleton to the plasma membrane, we investigated whether NHE1 affects cortical stiffness of MV3 cells, and how this makes an impact on their invasiveness. METHODS: NHE1 overexpressing MV3 cells were compared to the corresponding mock-transfected control cells. NHE1 expression was verified by Western blotting, cariporide (HOE642) was used to inhibit NHE1 activity, cell stiffness was determined by atomic force microscopy, and F-actin was visualized by phalloidin-staining. Migration on, and invasion of, native and glutaraldehyde-fixed collagen I substrates were analyzed using time-lapse video microscopy and Boyden-chamber assays, respectively. MMP secretion and activity were detected by Western blot and zymography, respectively. MMP activity was inhibited with NNGH. RESULTS: The cortical, but not the bulk stiffness, was significantly higher in NHE1 overexpressing cells. This increase in cortical stiffness was accompanied by a reorganization of the cortical cytoskeleton, i.e. a condensation of F-actin underneath and along the plasma membrane. However, it was not affected by NHE1 inhibition. Nevertheless, actin dynamics is required for cell invasion as demonstrated with the application of cytochalasin D. NHE1 overexpression was associated with an elevated MMP3 secretion and an increase in the invasion of a native matrix. This increase in invasiveness could be antagonized by the MMP inhibitor NNGH. Transmigration through a glutaraldehyde-fixed, indigestible substrate was not affected by NHE1 overexpression. CONCLUSION: NHE1, as a structural element and independently of its transport activity, contributes to the organization of the cortical F-actin meshwork and thus impacts cortical stiffness. Since NHE1 overexpression stimulates MMP3 secretion but does not change transmigration through a fixed substrate, MV3 cell invasion of a native substrate depends on MMP activity rather than on a modifiable cortical stiffness.

Establishing risk-adjusted quality indicators in surgery using administrative data-an example from neurosurgery.

BACKGROUND: The current draft of the German Hospital Structure Law requires remuneration to incorporate quality indicators. For neurosurgery, several quality indicators have been discussed, such as 30-day readmission, reoperation, or mortality rates; the rates of infections; or the length of stay. When comparing neurosurgical departments regarding these indicators, very heterogeneous patient spectrums complicate benchmarking due to the lack of risk adjustment. OBJECTIVE: In this study, we performed an analysis of quality indicators and possible risk adjustment, based only on administrative data. METHODS: All adult patients that were treated as inpatients for a brain or spinal tumour at our neurosurgical department between 2013 and 2017 were assessed for the abovementioned quality indicators. DRG-related data such as relative weight, PCCL (patient clinical complexity level), ICD-10 major diagnosis category, secondary diagnoses, age and sex were obtained. The age-adjusted Charlson Comorbidity Index (CCI) was calculated. Logistic regression analyses were performed in order to correlate quality indicators with administrative data. RESULTS: Overall, 2623 cases were enrolled into the study. Most patients were treated for glioma (n = 1055, 40.2%). The CCI did not correlate with the quality indicators, whereas PCCL showed a positive correlation with 30-day readmission and reoperation, SSI and nosocomial infection rates. CONCLUSION: All previously discussed quality indicators are easily derived from administrative data. Administrative data alone might not be sufficient for adequate risk adjustment as they do not reflect the endogenous risk of the patient and are influenced by certain complications during inpatient stay. Appropriate concepts for risk adjustment should be compiled on the basis of prospectively designed registry studies.

Regression of Pineal Lesions: Spontaneous or Iatrogenic? A Case Report and Systematic Literature Review.

BACKGROUND: Tumors arising from the pineal region account for approximately 1% of intracranial neoplasms. We present a case of a previously healthy 5-year-old boy with an acute onset of headache. A magnetic resonance imaging (MRI) scan showed a pineal mass with aqueduct compression. The patient was scheduled for tumor resection. An endoscopic third ventriculostomy was performed in advance for the treatment of hydrocephalus. Afterwards, MRI showed a relevant regression of the pineal mass without specific treatment. Consequently, surgery was cancelled and further MRI follow-up showed a regression of the mass and a constant tumor mass over a period of 30 months. Spontaneous regression of malignant tumors is a rare phenomenon with an incidence of 1 of 60,000-100,000 cases. Only a few cases with spontaneous regression of pineal tumors have been reported. METHODS: We performed a systematic literature review according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines on spontaneously regressing pineal lesions and found 13 cases in the literature. RESULTS: Six hypotheses for explaining tumor regression were found, comprising treatment with steroids, effects of diagnostic irradiation, treatment of hydrocephalus, pineal apoplexy, surgical trauma, and immunologic mechanisms. None of these mechanisms was evidentiary. However, in all reported cases, some kind of treatment (e.g. treatment of hydrocephalus, application of steroids, and so on) has been performed before tumor regression. CONCLUSIONS: The clinician has to bear in mind that regression of pineal tumors might be triggered by use of steroids, for example, and in cases of improvement of the patient's presenting symptoms, new MRI scans should be performed.