Adverse events during endovascular treatment of ruptured aneurysms: A prospective nationwide study on subarachnoid hemorrhage in Sweden.

Introduction: A range of adverse events (AEs) may occur in patients with subarachnoid hemorrhage (SAH). Endovascular treatment is commonly used to prevent aneurysm re-rupture. Research question: The aim of this study was to identify AEs related to endovascular treatment, analyze risk factors for AEs and how AEs affect patient outcome. Material and methods: Patients with aneurysmal SAH admitted to all neurosurgical centers in Sweden during a 3.5-year period (2014-2018) were prospectively registered. AEs related to endovascular aneurysm treatment were thromboembolic events, aneurysm re-rupture, vessel dissection and puncture site hematoma. Potential risk factors for the AEs were analyzed using multivariate logistic regression. Functional outcome was assessed at one year using the extended Glasgow outcome scale. Results: In total, 1037 patients were treated for ruptured aneurysms. Of which, 715 patients were treated with endovascular occlusion. There were 115 AEs reported in 113 patients (16%). Thromboembolic events were noted in 78 patients (11%). Aneurysm re-rupture occurred in 28 (4%), vessel dissection in 4 (0.6%) and puncture site hematoma in 5 (0.7%). Blister type aneurysm, aneurysm smaller than 5 mm and endovascular techniques other than coiling were risk factors for treatment-related AEs. At follow-up, 230 (32%) of the patients had unfavorable outcome. Patients suffering intraprocedural aneurysm re-rupture were more likely to have unfavorable outcome (OR 6.9, 95% CI 2.3-20.9). Discussion and conclusion: Adverse events related to endovascular occlusion of a ruptured aneurysm were seen in 16% of patients. Aneurysm re-rupture during endovascular treatment was associated with increased risk of unfavorable functional outcome.

Serum neurofilament light as a predictor of outcome in subarachnoid haemorrhage.

BACKGROUND: Prognostication of clinical outcome in patients suffering from aneurysmal subarachnoid haemorrhage (SAH) is a challenge. There are no biochemical markers in routine use that can aid in prognostication. Neurofilament light (NFL) measured in cerebrospinal fluid (CSF) has been associated with clinical outcome in previous studies. OBJECTIVE: To investigate if serum levels of NFL correlate with CSF levels and long-term clinical outcome in patients suffering from SAH. METHODS: We conducted an observational cohort study of 88 patients treated for SAH at Umeå University Hospital in 2014-2018. Serum and CSF samples were analysed using an enzyme-linked immunosorbent assay to quantify NFL levels. Outcome was assessed using Glasgow Outcome Scale Extended and dichotomised as favourable or unfavourable. Differences in NFL levels between outcome groups were analysed using repeated measurements ANOVA. Relationship between CSF and serum NFL levels was analysed using Pearson's correlation. A multivariate binary logistic regression model and a receiver operation characteristic curve were used to assess the predictive value of serum NFL. RESULTS: A significant correlation between serum and CSF-NFL levels could be seen (Pearson's correlation coefficient = 0.7, p < .0001). Mean level of serum NFL was higher in the unfavourable outcome group than the favourable outcome group (p < .0001), in all epochs of SAH, and correlated with initial disease severity on the World Federation of Neurosurgical Societies scale. Serum NFL in the late phase displayed the best predictive potential in a receiver operation characteristic curve analysis (AUC=0.845, p < .0001). CONCLUSION: Levels of NFL in serum and CSF are correlated. Early serum NFL levels seem to reflect initial tissue damage and serum NFL levels in the late phase may reflect secondary events such as vasospasm or delayed cerebral ischemia. Serum NFL may be used as a prognostic marker of clinical outcome in SAH.

Adverse events associated with microsurgial treatment for ruptured intracerebral aneurysms: a prospective nationwide study on subarachnoid haemorrhage in Sweden.

BACKGROUND: Adverse events (AEs) or complications may arise secondary to the treatment of aneurysmal subarachnoid haemorrhage (SAH). The aim of this study was to identify AEs associated with microsurgical occlusion of ruptured aneurysms, as well as to analyse their risk factors and impact on functional outcome. METHODS: Patients with aneurysmal SAH admitted to the neurosurgical centres in Sweden were prospectively registered during a 3.5-year period (2014-2018). AEs were categorised as intraoperative or postoperative. A range of variables from patient history and SAH characteristics were explored as potential risk factors for an AE. Functional outcome was assessed approximately 1 year after the bleeding using the extended Glasgow Outcome Scale. RESULTS: In total, 1037 patients were treated for ruptured aneurysms, of which, 322 patients were treated with microsurgery. There were 105 surgical AEs in 97 patients (30%); 94 were intraoperative AEs in 79 patients (25%). Aneurysm rerupture occurred in 43 patients (13%), temporary occlusion of the parent artery >5 min in 26 patients (8%) and adjacent vessel injury in 25 patients (8%). High Fisher grade and brain oedema on CT were related to increased risk of AEs. At follow-up, 38% of patients had unfavourable outcome. Patients suffering AEs were more likely to have unfavourable outcome (OR 2.3, 95% CI 1.10 to 4.69). CONCLUSION: Intraoperative AEs occurred in 25% of patients treated with microsurgery for ruptured intracerebral aneurysm in this nationwide survey. Although most operated patients had favourable outcome, AEs were associated with increased risk of unfavourable outcome.

The impact of previous health on the mortality after aneurysmal subarachnoid hemorrhage: analysis of a prospective Swedish multicenter study.

PURPOSE: There is an an increasing awareness of the importance of health and lifestyle for stroke diseases like spontaneous subarachnoid hemorrhage (SAH). However, the importance of pre-existing medical conditions for clinical course and mortality after SAH has not been studied. The aim of the present study was to identify pre-existing conditions contributing to mortality after SAH. METHODS: Data were extracted from a Swedish national prospective study on patients with SAH. Variables were defined for age, sex, body mass index (BMI), clinical condition at admission, and for 10 pre-existing medical conditions. Models predicting mortality in three time intervals with all possible subsets of these variables were generated, compared and selected using Akaike's information criterion. RESULTS: 1155 patients with ruptured aneurysms were included. The mortality within 1 week was 7.6%, 1 month 14.3%, and 1 year 18.7%. The most common pre-existing medical conditions were smoking (57.6%) and hypertension (38.7%). The model's best predicting mortality within 1 week and from 1 week to 1 month included only the level of consciousness at admission and age, and these two variables were present in all the models among the top 200 in Akaike score for each time period. The most predictive model for mortality between 1 month and 1 year added previous stroke, diabetes, psychiatric disease, and BMI as predictors. CONCLUSION: Mortality within the first month was best predicted simply by initial level of consciousness and age, while mortality within from 1 month to 1 year was significantly influenced by pre-existing medical conditions.

Serum S100B correlates with health-related quality of life and functional outcome in patients at 1 year after aneurysmal subarachnoid haemorrhage.

BACKGROUND: Early, objective prognostication after aneurysmal subarachnoid haemorrhage (aSAH) is difficult. A biochemical marker would be desirable. Correlation has been found between levels of the protein S100 beta (S100B) and outcome after aSAH. Timing and clinical usefulness are under investigation. METHODS: Eighty-nine patients admitted within 48 h of aSAH were included. Modified ranking scale (mRS), EuroQoL health-related quality of life measure (EQ-5Dindex) and EuroQoL visual analogue scale (EQ-VAS) values were evaluated after 1 year. S100B was measured in blood samples collected at admission and up to day 10. RESULTS: S100B correlated significantly with EQ-5Dindex and mRS, but not EQ-VAS at 1 year after aSAH. A receiver operating characteristic analysis for peak S100B values (area under the curve 0.898, 95% confidence interval 0.828-0.968, p < 0.0001), with a cutoff of 0.4 µg/l, yielded 95.3% specificity and 68% sensitivity for predicting unfavourable outcome. Dichotomized S100B (> 0.4 µg/l vs ≤ 0.4 µg/l), age and Hunt and Hess grading scale score (HH) were associated with unfavourable mRS outcome in univariate logistic regression analysis. Dichotomized S100B was the only variable independently correlated with unfavourable mRS outcome in a multivariate logistic regression analysis. CONCLUSIONS: For the first time, S100B was shown to correlate with mRS and health-related quality of life at 1 year after aSAH. Peak S100B can be used as a prognostic factor for unfavourable outcome measured as dichotomized mRS after aSAH. A peak value cutoff of 0.4 µg/l is suggested. Ethical approval no: 2013/366-31, 4th of February 2014.

A case report of a complete degloving injury of the penile skin.

INTRODUCTION: Male genital degloving injuries are unusual and rarely caused by animal bite. Usually patients attend health care immediately if bitten in the genital area. Prophylactic antibiotics is routinely used (Gomes et al., 2000). A penile degloving usually begins just proximal of the coronal line and progress down to the base of the shaft. Deep erectile tissue and the spermatic cord are seldom damaged and the endogenous skin of glans usually survives (Brown and Fryer, 1957; Morey et al., 2004; Finical and Arnold, 1999). PRESENTATION OF CASE: A heavily smoking man with a previous history of bladder cancer presented himself to the emergency department 24h after a dog bite degloved his penis. The avulsed skin was necrotic and subsequently excised. Antibiotic treatment was started. A bacterial swab was found positive for canine oral flora. The skin defect was closed using a 1:1 meshed split thickness skin graft from the inner thigh. Smoking cessation was encouraged. At the three month follow up the patient expressed satisfaction with both cosmetic and functional result and was now non-smoking. DISCUSSION: Several approaches to reconstruct penile skin exist. Split thickness skin graft has been lifted as a preferable alternative (Brown and Fryer, 1957; Finical and Arnold, 1999; Paraskevas et al., 2003) [5]. In this case, the avulsed skin was necrotic and could not be used. A 1:1 meshed split-thickness graft was chosen with excellent results. CONCLUSION: 1:1mesh of the graft can be recommended for easy attachment with a good functional and esthetical result. The potential risk of losing intimacy appearance or having to go through repeated procedures in the genital area motivated smoking cessation for this patient.

Predictors of Reoperations in Deep Inferior Epigastric Perforator Flap Breast Reconstruction.

BACKGROUND: The deep inferior epigastric perforator (DIEP) procedure is regarded a safe option for autologous breast reconstruction. Reoperations, however, may occur, and there is no consensus in the literature regarding the risk factors. The aim of this study was to identify factors associated with reoperations in DIEP procedure. PATIENTS AND METHODS: A retrospective study of consecutive patients undergoing DIEP breast reconstruction 2007 to 2014 was performed and included a review of 433 medical charts. Surgical outcome was defined as any unanticipated reoperation requiring return to the operating room. Multivariate regression analysis was utilized to identify predictors of reoperation. The following factors were considered: age, body mass index, comorbidity, childbearing history, previous abdominal surgery, adjuvant therapy, reconstruction laterality and timing, flap and perforator characteristics, and number and size of veins. RESULTS: In total, 503 free flaps were performed in 433 patients, 363 (83.8%) unilateral and 70 (16.2%) bilateral procedures. Mean age was 51 years; 15.0% were obese; 13.4% had hypertension; 2.3% had diabetes; 42.6% received tamoxifen; 58.8% had preoperative radiotherapy; 45.6% had abdominal scars. Reoperation rate was 15.9% (80/503) and included flap failure, 2.0%; partial flap loss, 1.2%; arterial thrombosis, 2.0%; venous thrombosis, 0.8%; venous congestion, 1.2%; vein kinking, 0.6%. Other complications included bleeding, 2.2%; hematoma, 3.0%; fat necrosis, 2.8%, and infection, 0.2%. Factors negatively associated with reoperation were childbearing history (odds ratio [OR]: 3.18, P = 0.001) and dual venous drainage (OR: 1.91, P = 0.016); however, only childbearing remained significant in the multivariate analyses (OR: 4.56, P = 0.023). CONCLUSIONS: The history of childbearing was found to be protective against reoperation. Number of venous anastomoses may also affect reoperation incidence, and dual venous drainage could be beneficial in nulliparous patients.

Neuroprotective effects of human spinal cord-derived neural precursor cells after transplantation to the injured spinal cord.

To validate human neural precursor cells (NPCs) as potential donor cells for transplantation therapy after spinal cord injury (SCI), we investigated the effect of NPCs, transplanted as neurospheres, in two different rat SCI models. Human spinal cord-derived NPCs (SC-NPCs) transplanted 9 days after spinal contusion injury enhanced hindlimb recovery, assessed by the BBB locomotor test. In spinal compression injuries, SC-NPCs transplanted immediately or after 1 week, but not 7 weeks after injury, significantly improved hindlimb recovery compared to controls. We could not detect signs of mechanical allodynia in transplanted rats. Four months after transplantation, we found more human cells in the host spinal cord than were transplanted, irrespective of the time of transplantation. There was no focal tumor growth. In all groups the vast majority of NPCs differentiated into astrocytes. Importantly, the number of surviving rat spinal cord neurons was highest in groups transplanted acutely and subacutely, which also showed the best hindlimb function. This suggests that transplanted SC-NPCs improve the functional outcome by a neuroprotective effect. We conclude that SC-NPCs reliably enhance the functional outcome after SCI if transplanted acutely or subacutely, without causing allodynia. This therapeutic effect is mainly the consequence of a neuroprotective effect of the SC-NPCs.

Distinct turnover of alternatively spliced isoforms of the RET kinase receptor mediated by differential recruitment of the Cbl ubiquitin ligase.

Alternative splicing of transcripts encoding the RET kinase receptor leads to isoforms differing in their cytoplasmic tail. Although in vitro studies have demonstrated a higher transforming activity of the long RET isoform (RET51), only the short isoform (RET9) can rescue the effects of a RET null mutation in the enteric nervous system and kidney development. The molecular basis underlying the distinct functions of the two RET isoforms is not understood. Here we demonstrated that activated RET51 associated more strongly with the ubiquitin ligase Cbl than did RET9, leading to increased ubiquitylation and faster turnover of RET51. The association of Cbl with RET was indirect and was mediated through Grb2. A constitutive complex of Grb2 and Cbl could be recruited to both receptor isoforms via docking of Shc to phosphorylated Tyr-1062 in RET. A mutant Shc protein unable to recruit the Grb2.Cbl complex decreased the turnover and prolonged the half-life of RET9, thus ascribing a previously unknown negative role to the Shc adaptor molecule. In addition, phosphorylation of Tyr-1096, which is present in RET51 but absent in RET9, endowed the longer isoform with a second route to recruit the Grb2.Cbl complex. These findings establish a mechanism for the differential down-regulation of RET9 and RET51 signaling that could explain the apparently paradoxical activities of these two RET isoforms. More generally, these results illustrate how alternative splicing can regulate the half-life and function of a growth factor receptor.