Patient, Relative and Staff Experiences of Clinical Trial Participation in Neurooncology: "Maybe You Can Also Show the Positive, No Matter How It Ends".

Purpose: There is a lack of evidence regarding how patients with malignant brain tumor and their relatives experience participation in neurooncological clinical trials. Similarly, insights from the perspective of trial staff caring for this group of patients are missing. This study aims to investigate patient, relative and trial staff experiences regarding participation in clinical neurooncological trials. Methods: Within a qualitative exploratory study, 29 semi-structured interviews with brain tumor patients, relatives and trial staff were conducted and analyzed using reflexive thematic analysis (RTA) by Braun and Clarke. A patient researcher and patient council were involved in data analysis and interpretation. Results: Four themes were developed reflecting significant aspects of the trial experience: 1. "It all revolves around hope"; 2. "Trial participation: experiencing unique medical care"; 3. "Everyone's roles are changing"; 4. "Communication as a possible area of conflict". Experiencing trial participation and general medical treatment were found to be interconnected to such a degree that they were often not meaningfully distinguished by patients and relatives. Conclusion: In addition to assessing traditional endpoints for patient outcomes, we recommend increased emphasis on investigating the impact of the "soft" components constituting trial participation. Due to the interconnectedness of medical treatment and trial participation, we recommend further investigation in comparison to experiences in regular care. A deeper understanding of trial participation is needed to inform improvements for patient experiences and staff satisfaction alongside medical and scientific progress.

The treatment options available to patients with (malignant) brain tumors are currently very limited. Therefore, patients are sometimes offered to participate in a clinical trial. This means that they receive an experimental treatment (eg new medicine) for which it is not yet clear whether it works better than regular medical care. Currently, little is known about how this group of patients, their relatives and the hospital staff who care for them experience the participation in these clinical trials ­ which is what we aimed to explore in our study reported here. Based on interviews with patients, relatives and staff, we found that: trial participation mainly revolves around hope;trial participation entails experiencing unique medical care;trial participation significantly changes the previous roles of patients, relatives and staff;trial participation intensifies communication as a possible area of conflict. By providing information on how patients, relatives and staff make sense of their trial experiences, this study constitutes an important addition to the traditional focus of clinical trials on medical and scientific endpoints (eg progression-free survival). This may help clinicians and researchers involved in cancer research and treatment to understand why "unsuccessful" trials can still be perceived as positive by patients or how hopeful communication may support their patients even when perceived as "unrealistic" from the clinicians' perspective. An in depth understanding of trial participation from the perspective of those affected is needed for improved care experiences alongside medical and scientific progress for cancer treatment.

Incomplete sensorimotor paresis after upper abdominal surgery with TEA and spinal epidural lipomatosis: a case report.

INTRODUCTION: This case report documents a postoperative, incomplete sensorimotor paraparesis from thoracic vertebral body 6 (Th6) after combined anesthesia for upper abdominal surgery in a patient who had a thoracic localization of spinal epidural lipomatosis (SEL). CASE PRESENTATION: The patient was treated in our clinic with a thoracic epidural catheter (TEA) for perioperative analgesia during a partial duodenopancreatectomy. Paraparetic symptoms occurred 20 hours after surgery. Initial MRI did not show bleeding, infection or spinal cord damage and the neurosurgeon consultants recommended observation. The neurological examination and the third follow-up MRI on 15th postoperative day showed ventrolateral damage of the spinal cord at level Th6. It is possible that local anesthetic compressed the spinal cord in addition to the existing lipomatosis and the thoracic kyphosis. The paraparesis improved during follow-up paraplegiologic treatment. CONCLUSION: So far, only two uncomplicated lumbar epidural catheter anesthesias have been described in patients who had a lumbar SEL. Epidural catheter anesthesia is a safe and effective method of pain control. But it is important to carefully identify and stratify patients with risk factors during the premedication visit. In patients who had kyphosis and thoracic localization of SEL, TEA may only be used after a risk-benefit assessment.

Optimal thresholds to predict long-term outcome after complete endovascular recanalization in acute anterior ischemic stroke.

BACKGROUND: Despite complete endovascular recanalization, a significant percentage of patients with acute anterior stroke do not achieve a good clinical outcome. We analyzed optimal thresholds of relevant parameters to discern functional independence after successful endovascular recanalization and test their predictive performance. METHODS: Patients with acute anterior ischemic stroke undergoing endovascular treatment between April 2015 and November 2019 were retrospectively analyzed. Only patients with premorbid modified Rankin Scale (mRS) score <3 and complete recanalization (modified Thrombolysis In Cerebral Infarction 2c/3) were included. Optimal thresholds of the most important variables predicting functional independence (mRS 0-2 after 90 days) were calculated using receiver operating characteristic curves and their predictive performance was tested in an independent dataset using machine learning algorithms. RESULTS: Overall, 371 patients met the inclusion criteria. Optimal thresholds for the overall most important variables to predict functional independence were (1) National Institutes of Health Stroke Scale (NIHSS) score ≤5 after 24 hours (area under the curve (AUC) 0.88 (95% CI 0.84 to 0.92)); (2) Alberta Stroke Program Early CT Score (ASPECTS) ≥7 on follow-up CT (AUC 0.72 (95% CI 0.68 to 0.77)); and (3) change in NIHSS score ≥8 after 24 hours (AUC 0.70 (95% CI 0.65 to 0.74)). The performance of these thresholds to predict a good outcome using machine learning in the independent dataset was evaluated for (1) NIHSS score ≤5 after 24 hours (AUC 0.76 (95% CI 0.71 to 0.81)); (2) follow-up ASPECTS ≥7 (AUC 0.64 (95% CI 0.58 to 0.70)); (3) change in NIHSS score ≥8 after 24 hours (AUC 0.61 (95% CI 0.55 to 0.67)); and (4) the combination of all three parameters (AUC 0.84 (95% CI 0.80 to 0.88)). CONCLUSIONS: After complete recanalization in acute anterior circulation ischemic stroke, a good long-term outcome could be accurately predicted reaching NIHSS score ≤5 after 24 hours.

Electronic Alberta Stroke Program Early CT score change and functional outcome in a drip-and-ship stroke service.

BACKGROUND: Debate continues as to whether patients with acute ischemic stroke with (suspected) large vessel occlusion benefit from direct referral versus secondary transportation. AIMS: To analyze the change in early infarct signs, collaterals, and acute ischemia volume and their association with transfer time and functional outcome. METHODS: We retrospectively analyzed consecutive transfers between 2013 and 2016 for patients with anterior circulation stroke transported from referring hospitals to our center as potential candidates for thrombectomy. Alberta Stroke Programme Early CT Scores (ASPECTS) were automatically calculated on external and in-house CT using the Brainomix e-ASPECTS software, and collaterals were assessed using the e-CTA tool. Functional status after stroke using the modified Rankin scale (mRS) was obtained. RESULTS: 102 patients with CT scans both at the referring hospital and our center were identified. During patient transfer, e-ASPECTS declined by a median of 1 point (0-2). Functional outcome correlated with the change in e-ASPECTS (decline, n=54) (Spearman rs =0.322, 95% CI 0.131 to 0.482, p=0.001). The median image-to-image time was 149 min (IQR 113-190), but did not correlate with change in e-ASPECTS (p=0.754) and mRS score at 3 months (p=0.25). Preserved good collateral status assessed at the comprehensive stroke center was associated with better functional outcome (rs =-0.271, 95% CI -0.485 to -0.037, p=0.02). CONCLUSIONS: Patient transfer in a drip-and-ship network was associated with declines in e-ASPECTS associated with worse functional outcome. Image-to-image time did not influence this association, but worsening collateral status did.

Management of Spinal Emergencies in Patients on Direct Oral Anticoagulants.

OBJECTIVE: Spine surgeons increasingly encounter acute spinal pathologies in patients treated with direct oral anticoagulants (DOACs), but only limited data on the management of these patients are currently available. METHODS: We retrospectively analyzed patients who presented to our department with acute spinal pathology during treatment with DOAC and who required urgent surgical therapy. Patient characteristics and treatment modalities were studied, with specific focus on the management of hemostasis and surgical therapy. Furthermore, we analyzed 19 cases of spinal emergencies during DOAC treatment reported in the literature. RESULTS: A total of 12 patients were identified and included in the present analysis. Patients suffered from acute spinal cord compression caused by spinal tumor manifestation (n = 5), empyema (n = 4), degenerative spinal stenosis (n = 1), hematoma (n = 1), and vertebral body fracture/dislocation (n = 2). All patients underwent emergency surgical treatment. Prohemostatic substances were administered perioperatively in 10 patients (83%) and included administration of prothrombin complex concentrates (83%), tranexamic acid (17%), and transfusion of platelets (8%). A total of 9 patients (75%) showed postoperative improvement of neurologic symptoms, and the in-hospital mortality in this patient cohort was 17%. CONCLUSIONS: Emergency spine surgery is feasible and should be considered in patients on treatment with DOAC. The (low) risk of intraoperative bleeding complications has to be weighed against the risk of permanent disability if surgical decompression is delayed. Administration of prothrombin complex concentrates and tranexamic acid may improve the coagulation before surgery, especially in cases of unavailable specific antidotes.

Epidemiologic features, risk factors, and outcome of sepsis in stroke patients treated on a neurologic intensive care unit.

PURPOSE: Because of the immune-suppressive effect of cerebral damage, stroke patients are at high risk for infections. These might result in sepsis, which is the major contributor to intensive care unit (ICU) mortality. Although there are numerous studies on infections in stroke patients, the role of sepsis as a poststroke complication is unknown. METHODS: We retrospectively analyzed incidence of and risk factors for sepsis acquisition as well as outcome parameters of 238 patients with ischemic or hemorrhagic strokes consecutively admitted to the neurologic ICU in a tertiary university hospital between January 1, 2009, and December 31, 2010. Basic demographic and clinical data including microbiological parameters as well as factors describing stroke severity (eg, lesion volume and National Institute of Health stroke scale score) were recorded and included into the analysis. The diagnosis of sepsis was based on the criteria of the German Sepsis Society. RESULTS: We identified 30 patients (12.6%) with sepsis within the first 7 days from stroke onset. The lungs were the most frequent source of infection (93.3%), and gram-positive organisms were dominating the microbiologic spectrum (52.4%). Comorbidities (chronic obstructive pulmonary disease and immunosuppressive disorders) and Simplified Acute Physiology Score II but none of the factors describing stroke severity were independent predictors of sepsis acquisition. Sepsis was associated with a significantly worse prognosis, leading to a 2-fold increased mortality rate during in-hospital care (36.7% vs 18.8%) and after 3 months (56.5% vs 28.5%), but only in the subgroup of supratentorial hemorrhages, it was an independent predictor of in-hospital and 3-month mortality. Other factors significantly associated with death in a multivariate analysis were chronic obstructive pulmonary disease, malignancies (in-hospital mortality only), and Simplified Acute Physiology Score II (3-month mortality only) for ischemia and heart failure (in-hospital mortality only), National Institute of Health stroke scale score (in-hospital mortality only), and stroke volume for hemorrhages, respectively. CONCLUSIONS: Sepsis seems to be a frequent complication of stroke patients requiring neurologic ICU treatment. Predictors of sepsis acquisition in our study were comorbidities and severity of deterioration of physiological status, but not stroke severity. A better understanding of risk factors is important for prevention and early recognition, whereas knowledge of outcome may help in prognosis prediction. Further studies are needed to clarify the optimal preventive treatment for these patients.

Multi-focal occurrence of cortical dysplasia in epilepsy patients.

This study describes the existence and the clinical and electrophysiological features of multi-focal cortical dysplasia in epilepsy patients. Five patients with intractable focal epilepsy are reported. All patients underwent invasive presurgical video-electroencephalography monitoring. Localization of dysplastic areas was based on high-resolution magnetic resonance scanning, surface and intracranial electroencephalography. Four patients underwent epilepsy surgery. Histological findings in focal cortical dysplasia (FCD) were classified according to Palmini. In addition, genetic examinations were performed in order to assess possible mutations in the genes for tuberous sclerosis complex. In four patients, FCDs were located in the same hemisphere. One case presented with bilateral FCDs. In three patients seizures arose from two separate dysplastic areas and in one patient, one lesion showed only interictal activity. In one further patient, seizures started exclusively from the hippocampus. In two of three patients with removal of the FCDs, the histological subtype was identical (Palmini type 2) and in one patient, histology differed between the lesions. All operated patients became seizure-free. In patients with FCD type 2, germ-line mutations in the tuberous sclerosis complex genes were not detectable. Dysplastic brain regions may not be restricted to a single brain region. Areas of FCD can have different degrees of epileptogenicity, ranging from electrographic silence to interictal epileptic discharges and initial involvement in seizure generation. Based on genetic analysis and clinical features, multi-FCD in this patient series was not likely to be related to tuberous sclerosis.

Focal cortical dysplasia: a genotype-phenotype analysis of polymorphisms and mutations in the TSC genes.

PURPOSE: Focal cortical dysplasia (FCD) is a common cause of pharmacoresistant human epilepsy. FCD has frequently been discussed as a "forme fruste" of tuberous sclerosis complex (TSC) because of the radiologic and histologic resemblance of dysplastic areas to tubers in TSC. Mutations or a germ-line predisposition in terms of increased polymorphisms in the TSC genes have been presumed to influence the pathogenesis of FCD. A detailed genotype-phenotype analysis of these patients has not been performed so far. METHODS: In this study, 33 patients with FCD (among them 23 with FCD type 2 and 4 patients with multifocal FCD) were investigated (1) clinically as to dermatologic manifestations, retinal hamartoma, cardial rhabdomyoma, and renal angiomyolipoma, and (2) genetically by considering lesional brain tissue and blood using single strand conformation polymorphism (SSCP) electrophoresis and sequencing of the TSC1 and TSC2 genes. RESULTS: In the clinical examinations, no subtle features of TSC could be detected in this large group of patients with FCD, pointing to the fact that this is a different patient group without clinical overlap. Several sequence alterations were found in the TSC1 and TSC2 genes in both lesional brain tissue and blood of FCD patients, however, in similar frequencies to that of the normal population. Moreover, most of these sequence alterations were silent. DISCUSSION: This study shows that FCD-even multifocal FCD-is not caused by mutations in the TSC genes and seems not to be promoted by polymorphisms in the TSC genes. Therefore, FCD cannot be regarded as a "forme fruste" of TSC.