Prevention of Oxidative Damage in Spinal Cord Ischemia Upon Aortic Surgery: First-In-Human Results of Shock Wave Therapy Prove Safety and Feasibility.

Background Spinal cord ischemia (SCI) remains a devastating complication after aortic dissection or repair. A primary hypoxic damage is followed by a secondary damage resulting in further cellular loss via apoptosis. Affected patients have a poor prognosis and limited therapeutic options. Shock wave therapy (SWT) improves functional outcome, neuronal degeneration and survival in murine spinal cord injury. In this first-in-human study we treated 5 patients with spinal cord ischemia with SWT aiming to prove safety and feasibility. Methods and Results Human neurons were subjected to ischemic injury with subsequent SWT. Reactive oxygen species and cellular apoptosis were quantified using flow cytometry. Signaling of the antioxidative transcription factor NRF2 (nuclear factor erythroid 2-related factor 2) and immune receptor Toll-like receptor 3 (TLR3) were analyzed. To assess whether SWT act via a conserved mechanism, transgenic tlr3-/- zebrafish created via CRISPR/Cas9 were subjected to spinal cord injury. To translate our findings into a clinical setting, 5 patients with SCI underwent SWT. Baseline analysis and follow-up (6 months) included assessment of American Spinal Cord Injury Association (ASIA) impairment scale, evaluation of Spinal Cord Independence Measure score and World Health Organization Quality of Life questionnaire. SWT reduced the number of reactive oxygen species positive cells and apoptosis upon ischemia via induction of the antioxidative factor nuclear factor erythroid 2-related factor 2. Inhibition or deletion of tlr3 impaired axonal growth after spinal cord lesion in zebrafish, whereas tlr3 stimulation enhanced spinal regeneration. In a first-in-human study, we treated 5 patients with SCI using SWT (mean age, 65.3 years). Four patients presented with acute aortic dissection (80%), 2 of them exhibited preoperative neurological symptoms (40%). Impairment was ASIA A in 1 patient (20%), ASIA B in 3 patients (60%), and ASIA D in 1 patient (20%) at baseline. At follow-up, 2 patients were graded as ASIA A (40%) and 3 patients as ASIA B (60%). Spinal cord independence measure score showed significant improvement. Examination of World Health Organization Quality of Life questionnaires revealed increased scores at follow-up. Conclusions SWT reduces oxidative damage upon SCI via immune receptor TLR3. The first-in-human application proved safety and feasibility in patients with SCI. SWT could therefore become a powerful regenerative treatment option for this devastating injury.

Anxiety in caregiving partners of breast cancer patients.

PURPOSE: The aim of the present study was to determine the levels of anxiety of partners of breast cancer patients and to evaluate the differences of anxiety levels between patients and partners according to the stage of treatment, age and education level. METHODS: 57 spouses or domestic partners of breast cancer patients and 148 breast cancer patients participated in this prospective cohort study and filled out the questionnaires including the Spielberger state-trait-anxiety-inventory, as well as questions based on stress-triggering procedures during breast cancer diagnosis and therapy. RESULTS: State anxiety levels of partners were highest in partners who accompanied their patients when presenting for examinations and operations and tumorboard decisions (Mean State-Scores 52, 45 and 46.5). Anxiety scores were lowest at the stage of ongoing chemotherapy or follow-up. The 25% quartile of partners with the highest state anxiety levels had a significantly higher educational level (p = 0.023). Young men aged 18-35 years showed the highest levels of both trait and state anxiety. Partners showed significantly higher levels of anxiety than the patients for anesthetic complications (p < 0.001), e.g., fear of not waking up from general anesthetic and postoperative pain (p < 0.001). Patients showed significantly higher levels of anxiety for hairloss (p < 0.001), weight gain during chemotherapy (p < 0.001) and postoperative scars (p = 0.027). CONCLUSION: Breast cancer patients are much more concerned about body image issues than their male partners. As these body image-associated concerns often arise from the fear of loosing attraction to their partner, these fears might be reduced by speaking about them openly. Partners are mostly concerned about surgery and anesthetic-related complications. Therefore, preoperative medical information to the partner is mandatory. Partners of breast cancer patients should be included in psycho-oncological support and medical briefings. Probably high anxiety levels of both partners and patients should be taken into account (due to younger age, lower educational level and procedures causing distress). These partners and patients should receive extra careful (clarification) counselling and (treatment support such as a psycho-oncologist) involvement of a psyco-oncologist.

Treatment anxiety in breast cancer patients.

INTRODUCTION: The aim of the present study was to determine and evaluate the levels of anxiety of breast cancer patients according to the state of treatment, age and education level, as well as the anxiety potential of certain procedures during breast cancer treatment. METHOD: 148 breast cancer patients participated in this prospective cohort study and filled out the questionnaires including the Spielberger state-trait-anxiety-inventory, as well as questions based to stress triggering procedures during breast cancer therapy. The testing was accomplished with the Mann-Whitney U test, the significance level was set to 0.05. RESULTS: Patients who appeared for tumor board decision showed the highest state-anxiety levels (55.79 SD ± 18.73) followed by patients undergoing surgery (50.24 SD ± 13.84). Patients already undergoing chemotherapy had lower state-anxiety levels than the group of all other patients (p = 0.012). Women undergoing chemotherapy showed lower anxiety levels relating to many procedures of breast cancer treatment. The 25% quartile of patients with the highest levels in the trait score showed a significant poorer education level (p = 0.009). Age showed no statistical influence on the anxiety level of breast cancer patients.  CONCLUSION: Patients with probably high anxiety levels (younger age, low education level, and those appearing for frightening procedures) should receive extra careful clarification and treatment support such as a psycho-oncologist.