Impact of time to resumption of antithrombotic therapy on outcomes after surgical evacuation of chronic subdural hematoma: A multicenter cohort study.

BACKGROUND: The decision to resume antithrombotic therapy after surgical evacuation of chronic subdural hematoma (CSDH) requires judicious weighing of the risk of bleeding against that of thromboembolism. This study aimed to investigate the impact of time to resumption of antithrombotic therapy on outcomes of patients after CSDH drainage. METHODS: Data were obtained retrospectively from three tertiary hospitals in Singapore from 2010 to 2017. Outcome measures analyzed were CSDH recurrence and any thromboembolic events. Logistic and Cox regression tests were used to identify associations between time to resumption and outcomes. RESULTS: A total of 621 patients underwent 761 CSDH surgeries. Preoperative antithrombotic therapy was used in 139 patients. 110 (79.1%) were on antiplatelets and 35 (25.2%) were on anticoagulants, with six patients (4.3%) being on both antiplatelet and anticoagulant therapy. Antithrombotic therapy was resumed in 84 patients (60.4%) after the surgery. Median time to resumption was 71 days (IQR 29 - 201). Recurrence requiring reoperation occurred in 15 patients (10.8%), of which 12 had recurrence before and three after resumption. Median time to recurrence was 35 days (IQR 27 - 47, range 4 - 82 days). Recurrence rates were similar between patients that were restarted on antithrombotic therapy before and after 14, 21, 28, 42, 56, 70 and 84 days, respectively. Thromboembolic events occurred in 12 patients (8.6%), of which five had the event prior to restarting antithrombosis. CONCLUSIONS: Time to antithrombotic resumption did not significantly affect CSDH recurrence. Early resumption of antithrombotic therapy can be safe for patients with a high thromboembolic risk.

A facile and scalable in production non-viral gene engineered mesenchymal stem cells for effective suppression of temozolomide-resistant (TMZR) glioblastoma growth.

BACKGROUND: Mesenchymal stem cells (MSCs) serve as an attractive vehicle for cell-directed enzyme prodrug therapy (CDEPT) due to their unique tumour-nesting ability. Such approach holds high therapeutic potential for treating solid tumours including glioblastoma multiforme (GBM), a devastating disease with limited effective treatment options. Currently, it is a common practice in research and clinical manufacturing to use viruses to deliver therapeutic genes into MSCs. However, this is limited by the inherent issues of safety, high cost and demanding manufacturing processes. The aim of this study is to identify a facile, scalable in production and highly efficient non-viral method to transiently engineer MSCs for prolonged and exceptionally high expression of a fused transgene: yeast cytosine deaminase::uracil phosphoribosyl-transferase::green fluorescent protein (CD::UPRT::GFP). METHODS: MSCs were transfected with linear polyethylenimine using a cpg-free plasmid encoding the transgene in the presence of a combination of fusogenic lipids and ß tubulin deacetylase inhibitor (Enhancer). Process scalability was evaluated in various planar vessels and microcarrier-based bioreactor. The transfection efficiency was determined with flow cytometry, and the therapeutic efficacy of CD::UPRT::GFP expressing MSCs was evaluated in cocultures with temozolomide (TMZ)-sensitive or TMZ-resistant human glioblastoma cell lines. In the presence of 5-fluorocytosine (5FC), the 5-fluorouracil-mediated cytotoxicity was determined by performing colometric MTS assay. In vivo antitumor effects were examined by local injection into subcutaneous TMZ-resistant tumors implanted in the athymic nude mice. RESULTS: At > 90% transfection efficiency, the phenotype, differentiation potential and tumour tropism of MSCs were unaltered. High reproducibility was observed in all scales of transfection. The therapeutically modified MSCs displayed strong cytotoxicity towards both TMZ-sensitive and TMZ-resistant U251-MG and U87-MG cell lines only in the presence of 5FC. The effectiveness of this approach was further validated with other well-characterized and clinically annotated patient-derived GBM cells. Additionally, a long-term suppression (> 30 days) of the growth of a subcutaneous TMZ-resistant U-251MG tumour was demonstrated. CONCLUSIONS: Collectively, this highly efficient non-viral workflow could potentially enable the scalable translation of therapeutically engineered MSC for the treatment of TMZ-resistant GBM and other applications beyond the scope of this study.

Pseudoaneurysm Resulting in Rebleeding After Evacuation of Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is a devastating cerebrovascular disease with high morbidity and mortality. Branching pattern of the lenticulostriate arteries from the middle cerebral artery makes them susceptible to formation of microaneurysms, which have been implicated in hypertensive ICH. Recurrence of hematoma due to delayed development of pseudoaneurysm after initial surgical evacuation is uncommon. CASE DESCRIPTION: Our patient is a 61-year-old gentleman who underwent primary evacuation of a spontaneous right-sided ICH. The initial vascular imaging was unremarkable for any underlying vascular malformation. After initial neurologic recovery, the patient developed another rebleeding in the hematoma cavity nearly 10 days after presentation. A formal angiogram showed the presence of a pseudoaneurysm that was treated via endovascular means. CONCLUSIONS: The rates of rebleeding have ranged from 10%-40% in various studies and have been directly correlated with mortality. Since follow-up with angiograms are not a usual practice in spontaneous ICH management, such as pseudoaneurysmal rebleeds could go undiagnosed. This case report reinforces the need for a thorough angiographic evaluation in the event of a deviation from expected clinical course, rebleeding not in concordance with intraoperative findings and significantly delayed hematoma recurrence.

Development of a prognostic scoring system to predict risk of reoperation for contralateral hematoma growth after unilateral evacuation of bilateral chronic subdural hematoma.

Bilateral chronic subdural hematoma (bCSDH) is frequently drained unilaterally when the contralateral CSDH is small and asymptomatic. However, reoperation rates for contralateral CSDH growth can be high. We aimed to develop a prognostic scoring system to guide the selection of suitable patients for unilateral drainage of bCSDH. Data were collected retrospectively across three tertiary hospitals from 2010 to 2017 on all consecutive bCSDH patients aged 21 or above. Predictors of reoperation were identified using multivariable logistic regression. A prognostic score was developed and internally validated. 240 bCSDH patients were analyzed. 98 (40.8%) underwent unilateral and 142 (59.2%) underwent bilateral evacuation. Clinical outcomes were comparable between the unilateral and bilateral evacuation groups. Within the unilateral evacuation group, 4 (4.1%) had a reoperation for contralateral CSDH growth. Reoperation for contralateral CSDH was predicted by preoperative use of anticoagulants (OR = 15.0, 95% CI: 1.49-169.15, p = 0.017). Complete resolution of contralateral CSDH was predicted by its preoperative maximum width, with a cut-off of 9 mm producing the highest sensitivity and specificity (OR = 4.17 for ≤9 mm, 95% CI: 1.54-11.11, p = 0.004). Using our prognostic score, reoperation rate for contralateral CSDH was 1.6%, 3.6%, 16.7%, and 50.0% in low-risk, moderate-risk, high-risk and very high-risk patients, respectively. With each increase of 1 in the prognostic score, patients were 4 times as likely to undergo reoperation for contralateral CSDH (OR = 3.98, 95% CI: 1.36-13.53, p = 0.013). Our proposed risk score may be used as an adjunct in clinical decision making for bCSDH patients undergoing unilateral evacuation.

Right Parietal Skull Xanthoma Characterized as a Metastatic Deposit.

BACKGROUND: Xanthomas are benign lipomatous deposits that can be found systemically in various tissues including bones. Their presence in the skull remains a rare entity. Despite their benign characteristics, imaging modalities are often unable to distinguish them from malignant lesions. This leads to a diagnostic dilemma in patients with underlying malignancy. This case report highlights such a case where clinical history of prostate cancer and image findings were concordant with that of metastatic deposit in the parietal skull region. CASE DESCRIPTION: This 65-year-old gentleman was diagnosed with prostatic adenocarcinoma. During systemic workup for his tumor, he was found to have a right parietal skull lesion. Magnetic resonance imaging of the brain, as well as a bone scan, were consistent with that of a metastatic deposit. As treatment would be drastically affected by the diagnosis, an excision biopsy was performed. The histology was consistent with that of a bone xanthoma. CONCLUSIONS: Xanthomas are benign lesions that can be seen deposited in appendicular and axial skeleton. Skull lesions are rare with most case descriptions focusing on their presence in the frontoorbital regions and mandible and temporal bone. They usually have a benign course but may present with symptoms due to localized mass effect. Surgical intervention and histologic diagnosis may still be required in these lesions due to their lack of imaging characteristics that confirm their diagnosis through noninvasive methods.

Outcomes of Subdural Versus Subperiosteal Drain After Burr-Hole Evacuation of Chronic Subdural Hematoma: A Multicenter Cohort Study.

BACKGROUND: Although the use of a postoperative drain after burr-hole evacuation of chronic subdural hematoma (CSDH) is known to improve surgical outcomes, the superiority of subdural over subperiosteal drains has not been firmly established. Evidence comparing these 2 drain types is largely restricted to single-center series with limited numbers. Using a multicenter cohort study, we aimed to show noninferiority of subperiosteal drains vis-à-vis subdural drains after burr-hole evacuation of CSDH. METHODS: We performed a retrospective analysis of all consecutive patients with CSDH aged 21 years and older who had undergone burr-hole craniostomy across 3 tertiary hospitals from 2010 to 2017. Primary outcome measures included CSDH recurrence and modified Rankin Scale (mRS) score at 6 months. Outcomes of patients in the subdural and subperiosteal drain groups were analyzed and confounders were adjusted for using multivariate logistic regression. RESULTS: Of the 570 cases analyzed, 329 (57.7%) received a subdural drain and 241 (42.3%) received a subperiosteal drain. There was no significant difference between the 2 drain groups in CSDH recurrence (13.1% in the subdural group vs. 11.2% in the subperiosteal group; P = 0.502) or 6-month mRS score (27.2% with mRS 4-6 in the subdural group vs. 20.4% in the subperiosteal group; P = 0.188). Independent predictors of CSDH recurrence identified on multivariate analysis included premorbid mRS score 0-3 (P = 0.021), separated CSDH type on preoperative computed tomography scan (P = 0.002), and postoperative pneumocephalus of ≥15 mm (P = 0.005). CONCLUSIONS: Outcomes of subdural and subperiosteal drains after burr-hole craniostomy for CSDH are largely equivalent based on our findings.

Is anticoagulation for venous thromboembolism safe for Asian elective neurosurgical patients? A single centre study.

BACKGROUND: The incidence of venous thromboembolism (VTE) in neurosurgical patients ranges 3-24%. VTE is potentially fatal, and prophylactic anticoagulation is recommended worldwide. However, anticoagulation poses a risk of haemorrhage, which can be devastating. We aim to determine the incidence of VTE and risk of haemorrhage following anticoagulation. METHODS: Between 1 May 2014 and 1 May 2016, all patients who underwent elective neurosurgery were recruited into our study. All patients had bilateral lower limb ultrasound to screen for deep vein thrombosis (DVT) between post-operative days 3 and 7. These patients are also monitored for manifestations of pulmonary embolism (PE). If present, a computed tomography pulmonary angiogram will be performed. Patients with VTE will either receive conservative treatment or anticoagulation. RESULTS: During this period, 170 of 610 patients were included. Of the 170 patients, 17 patients (10.0%) developed DVT. Fifteen patients had cranial surgery and two patients had spinal surgery. Two patients (1.2%) developed PE and both patients had concurrent DVT. Of these 17 patients, nine patients received anticoagulation. Of these nine patients, six patients (66.7%) developed surgical site bleeding following anticoagulation and all of them required surgical intervention. Patients who were managed conservatively did not suffer haemorrhage. CONCLUSION: Our results show an overall 10.0% incidence of DVT and 1.2% incidence of PE following elective neurosurgery within this Asian cohort of neurosurgical patients. There is also a high risk (66.7%) of significant surgical site bleeding following anticoagulation.

Percutaneous pedicle screw fixation for thoracolumbar burst fracture: a Singapore experience.

INTRODUCTION: This study aimed to evaluate the clinical and radiological outcomes, and safety and efficacy of percutaneous pedicle screw fixation (PPSF) in the treatment of thoracolumbar burst fractures. METHODS: This was a retrospective review of patients with thoracolumbar burst fractures treated with PPSF in a single hospital from 2010 to 2011. Baseline data included patient demographics, mechanism of injuries, fracture level, neurologic status and the number of percutaneous screws inserted. Kyphotic angle correction, vertebral body height restoration and mid-sagittal canal diameter improvement were used to assess radiological outcome. Screw misplacement, operative complications, functional improvement (ASIA score) and pain score on visual analogue scale were used to assess safety and clinical outcomes. RESULTS: 21 patients with 25 thoracolumbar burst fractures were treated with 134 percutaneous screws. There was significant improvement in kyphotic angle correction (mean difference 6.1 degrees, p = 0.006), restoration of anterior and posterior vertebral height (mean difference 19.7%, p < 0.01 and mean difference 6.6%, p = 0.007, respectively) and mid-sagittal canal diameter (mean difference 15.6%, p = 0.007) on discharge. These improvements remained statistically significant at six months post operation for restoration of anterior vertebral body height (mean difference 9.8%, p = 0.05) and mid-sagittal diameter (mean difference 30.0%, p < 0.01). CONCLUSION: In this first local review, we have shown that PPSF is a relatively safe and effective technique for treating selected thoracolumbar burst fractures, and that it yields satisfactory results. However, its long-term outcome and efficacy need to be further evaluated.

Major workplace related accidents in Singapore: A major trauma centre's experience.

INTRODUCTION: Major workplace related accidents pose a significant healthcare resource challenge in Singapore. MATERIALS AND METHODS: Our study looks at the epidemiology of patients who were admitted for workplace related accidents, in a single institution, with an Injury Severity Score of >9. RESULTS: There were 196 cases of major workplace related accidents admitted between January 2006 and December 2007. The median age of patients admitted was 37 years with a large percentage being males (95.4%) and non-residents (57.1%). The most common ethnic group was Chinese (53.1%) followed by Indians (23.5%). The most common mechanism of injury was fall from height (66.3%) followed by injuries as a result of falling objects at work (21.9%). The percentage of patients who required surgical intervention was 69.9%. Patients admitted for major workplace related accidents had a median length of stay of 5 days in the hospital, a median length of 24 days of medical leave (ML), certifying them unfit for duty and the average cost of stay for each patient was S$11,000. CONCLUSIONS: We have a better understanding of the epidemiology and socio-economic impact of workplace related accidents through this study. Workplace related accidents result in significant number of man-days lost from work and monetary cost to employers, medical insurance and the hospital. With an improved understanding, we propose methods to prevent and reduce such accidents in future. A direct consequence of which will be the possible reduction of hospitalisation costs and better allocation of healthcare resources in the future.