Minimally invasive endoscopic evacuation with the novel, portable Axonpen neuroendoscopic system for spontaneous intracerebral hemorrhage.

Minimally invasive surgeries have shown potential to improve mortality and clinical outcomes of spontaneous intracerebral hemorrhage (ICH). The present study assessed the first-in-human outcomes of a novel, portable neuroendoscopic system for ICH evacuation at our single center. This neuroendoscopic system integrates real-time visualization into a handpiece which has controllable suction, irrigation, and coagulation to allow a neurosurgeon to conduct minimally invasive ICH evacuation independently with bimanual dexterity. Pre- and postoperative data of ten patients who had spontaneous basal ganglia hemorrhage (mean: 46.5 ± 12.2 mL) and underwent evacuation with the specified neuroendoscopic system were collected prospectively. The mean time to receive surgery was 12.1 ± 7.6 h. Mean operative time was 3.4 ± 0.9 h. The mean hematoma volume decreased to 6.0 ± 3.9 mL at postoperative 6 h, resulting in a mean volume reduction of 86.0 ± 11.2% (P = 0.005). The median length of intensive care unit stay was 3 days (IQR, 3-4 days). At discharge, the median Glasgow Coma Scale (GCS) score significantly improved to 11.5 (IQR, 11-15; P = 0.016), and the median modified Rankin Scale (mRS) score was 4 (IQR, 4-5). Six patients (60%) showed a favorable mRS score of ≤ 3 on their last return visit. Neither death nor rebleeding occurred during the follow-up periods. Integrated design of the innovative device is valuable to optimize minimally invasive endoscopic ICH evacuation procedure. Further studies are needed to clarify long-term benefits from such type of the innovative device to early intervention of ICH.

Endoport Assisted Endoscopic Surgery for Hypertensive Basal Ganglia Hemorrhage by Transsylvian Approach: Technical Nuances and Preliminary Clinical Results.

BACKGROUND: There is no clear evidence on the indication and surgical approaches on evacuating basal ganglia hemorrhage caused by hypertensive bleeding. Some studies have shown that minimally invasive approaches have therapeutic potentials, but its benefits remain inconclusive. We describe an endoport assisted endoscopic transsylvian approach for basal ganglia hemorrhage evacuation. We evaluate the safety and efficacy of this approach in a cohort study. METHODS: We included 19 patients (mean age 57 years) who underwent the surgery at a single county-level hospital in Yunan Province, China. The majority had a Glasgow coma scale between 9 and 12 on admission. The midline shift ranged from 16-29 mm (mean 19 mm). Hematoma volume ranged from 46 to 106 ml (mean 67 ml). Six patients (31.6%) presented with intraventricular hemorrhage. RESULTS: All patients achieved greater than 90% decrease in hematoma volume at postoperative computed tomography scan. The average operative time was 115 minutes and average blood loss of 44 ml. The most common postoperative complication was pulmonary infection (63.2%). No rebleeding, seizure, infectious meningitis, or postoperative mortality was observed. A total of 17 patients (89.5%) achieved good functional recovery at follow up within 90 days after surgery (Glasgow outcome scale 4-5) and 2 patients had severe disability (Glasgow outcome scale 3). CONCLUSIONS: Endoport assisted endoscopic surgery through transsylvian approach is safe and effective treatment for hypertensive basal ganglia hemorrhage. The majority of patients have good functional recovery and the rate of severe complications is low.

Comparison of endoscopic evacuation, craniotomy, and puncture aspiration for the treatment of spontaneous basal ganglia intracerebral hematoma.

OBJECTIVE: To compare the prognosis of patients with spontaneous basal ganglia intracerebral hematoma treated by endoscopic evacuation, craniotomy, or puncture aspiration. METHODS: This retrospective observational study included information from patients with basal ganglia hematoma who received craniotomy, endoscopic evacuation, or puncture aspiration in the Department of Neurosurgery of the First Affiliated Hospital of USTC between January 2016 and May 2021. Patients were grouped according to their treatment method for comparison. RESULTS: From a total of 184 patients, 62 cases (51 males, aged 54.44 ± 9.92 years) received craniotomy, 64 cases (45 males, aged 53.97 ± 11.87 years) received endoscopic evacuation, and 58 cases (43 males, aged 54.25 ± 10.35 years) received puncture aspiration. No significant difference was found in baseline characteristics among three surgical procedures. Patients in the endoscopy group had the shortest hospital stay (15.16 ± 4.89 days vs. 17.88 ± 5.97 and 20.77 ± 6.96 days), lowest infectious meningitis [1(1.6 %) vs. 2(3.4%) and 8(12.9%)] and pulmonary infection [3(4.7%) vs. 5(8.6%) and 13(21.0%)] rates, and highest hematoma removal rate (90.39 ± 5.22% vs. 35.87 ± 6.23 and 84.76 ± 4.91%) and Glasgow outcome scale 6 months after surgery (4.41 ± 0.53 vs. 3.74 ± 1.09 and 3.81 ± 1.03). The occurrence of gastrointestinal bleeding, epilepsy, and mortality were similar (all p > 0.05) among the groups. CONCLUSION: Patients with spontaneous basal ganglia intracerebral hematoma who received endoscopic evacuation might have better prognosis than those treated with craniotomy or puncture aspiration. In future, endoscopic surgery could become the most common method for treating spontaneous basal ganglia hemorrhages.

A case of spontaneous basal ganglia hemorrhage with contralateral extension utilizing the canal of Gratiolet.

BACKGROUND: Intracranial hemorrhage accounts for 10-20% of stroke etiologies annually. Basal ganglia is the most common site for intracranial hemorrhage accounting for 50% of all cases. Bilateral spontaneous basal ganglia hemorrhages (BGH) are rare with few reported cases. CASE PRESENTATION: We report an unusual case of a 69-year-old female who presented with a spontaneous bilateral basal ganglia hemorrhage secondary to a right BGH with contralateral extension through the anterior commissure (AC) utilizing the Canal of Gratiolet. Clinical course and imaging findings are discussed. CONCLUSIONS: To our knowledge, this is the first case to specifically detail the extension of spontaneous hemorrhage across the AC via the Canal of Gratiolet, and imaging findings provide a novel depiction of AC anatomy and fiber distribution in a clinical context. These findings may explain the mechanism behind this rare clinical entity.

Prognostic significance of perihematomal edema in basal ganglia hemorrhage after minimally invasive endoscopic evacuation.

OBJECTIVE: Spontaneous basal ganglia hemorrhage is a common type of intracerebral hemorrhage (ICH) with no definitive treatment. Minimally invasive endoscopic evacuation is a promising therapeutic approach for ICH. In this study the authors examined prognostic factors associated with long-term functional dependence (modified Rankin Scale [mRS] score ≥ 4) in patients who had undergone endoscopic evacuation of basal ganglia hemorrhage. METHODS: In total, 222 consecutive patients who underwent endoscopic evacuation between July 2019 and April 2022 at four neurosurgical centers were enrolled prospectively. Patients were dichotomized into functionally independent (mRS score ≤ 3) and functionally dependent (mRS score ≥ 4) groups. Hematoma and perihematomal edema (PHE) volumes were calculated using 3D Slicer software. Predictors of functional dependence were assessed using logistic regression models. RESULTS: Among the enrolled patients, the functional dependence rate was 45.50%. Factors independently associated with long-term functional dependence included female sex, older age (≥ 60 years), Glasgow Coma Scale score ≤ 8, larger preoperative hematoma volume (OR 1.02), and larger postoperative PHE volume (OR 1.03, 95% CI 1.01-1.05). A subsequent analysis evaluated the effect of stratified postoperative PHE volume on functional dependence. Specifically, patients with large (≥ 50 to < 75 ml) and extra-large (≥ 75 to 100 ml) postoperative PHE volumes had 4.61 (95% CI 0.99-21.53) and 6.75 (95% CI 1.20-37.85) times greater likelihood of long-term dependence, respectively, than patients with a small postoperative PHE volume (≥ 10 to < 25 ml). CONCLUSIONS: A large postoperative PHE volume is an independent risk factor for functional dependence among basal ganglia hemorrhage patients after endoscopic evacuation, especially with postoperative PHE volume ≥ 50 ml.

Good functional outcome following bilateral external capsule hemorrhage mimicking bilateral basal ganglia hemorrhage in a coma patient.

Simultaneous spontaneous bilateral external capsule hemorrhage is a rare clinical entity with extremely poor outcome. However, knowledge on the effective management of this fatal disease is limited. Herein,we described a case of a 42-year-old man with acute coma and quadriplegia as well as respiratory failure related to the disease. The patient underwent minimally invasive surgery plus local thrombolysis. Consequently, he recovered with satisfactory neurological function recovery on the 180th day of follow-up.

Spontaneous Bilateral Basal Ganglia Haemorrhage Secondary to Methanol Poisoning.

Methanol toxicity remains as major problem in the medical field.[1],[2],[3] With its active metabolite, formic acid often leads to severe metabolic acidosis and to some extend brain damaged.[4],[5],[6] We are reporting a case of brain hemorrhage at the right external capsule and left basal ganglia with mass effect and obstructive hydrocephalus in a methanol poisoning patient. A confused 29-year-old gentleman was brought into hospital. Initial investigation showed severe metabolic acidosis with raised anion gap. Initial brain CT scan was normal. Subsequently, serum methanol was reported to be high (112 mg/dL). Intravenous (IV) ethanol 10% was given without any delayed. As there was no improvement in his consciousness level, a repeat brain CT was performed and it showed multiple cerebral hemorrhage with obstructive hydrocephalus. Hence, clinicians should have high index of suspicion for cerebral hemorrhage in a patient with methanol toxicity, who presented with altered mental status and severe metabolic acidosis.

Spontaneous Bilateral Basal Ganglia Hemorrhage Due to Severe Hypertension.

Introduction: The basal ganglia, which comprise many subcortical nuclei, constitute an integrated functional unit of the brain. Spontaneous hemorrhage of the basal ganglia is mostly unilateral and secondary to uncontrolled hypertension. Simultaneous bilateral basal ganglia hemorrhage (SBBGH) is very rare. So far, only 40 cases have been documented so far. Case Presentation: Here, we report a 37-year-old man with a past medical history of uncontrolled hypertension who was brought to the emergency department due to severe headache, worsening confusion, and right-sided weakness for 2 days. An urgent non-contrast brain CT performed immediately revealed bilateral intracerebral hemorrhage (ICH) of the same age in the basal ganglia. On admission, blood pressure was 220/120. Other vital signs were normal. The patient was admitted to the ICU, IV antihypertensive and antiedema medications were given. After clinical improvement, he was transferred to the neurology ward on the fifth day. After another 5 days in the neurology inpatient ward, the patient clinically improved and was referred to the rehabilitation department. Conclusion: Due to the rarity of SBBGH, it is particularly interesting to report this remarkable case of a man with simultaneous spontaneous bilateral ganglia hemorrhage secondary to uncontrolled hypertension.

Smartphone navigated endoscopic port surgery of hypertensive basal ganglia hemorrhage.

OBJECTIVE: Endoscopic port surgery is a promising alternative for the surgical treatment of intracerebral hypertensive basal ganglia hemorrhage (HBGH). The precise location of hematoma is a crucial step for surgery. The authors developed a simple, low-cost navigation method using an Android smartphone for the localization of HBGH. METHODS: All patients' CT DICOM data were processed with an open-source software (3D Slicer). The volume of hematoma, angle, and length of trajectory were calculated automatically. A smartphone running the Android system and the Compass APP was used to help insert the inner introducer. An endoscopic port system was applied to create a working channel for neuro-endoscopic hematoma evacuation. RESULTS: There were 27 patients enrolled in this study (mean age 56). All patients underwent successful surgical evacuation of HBGH with neuroendoscopic evacuation. The mean time taken for the surgical plan was 4 min. The total operation time from skin incision to final suture was 82.6 min. Compared with standard neuronavigation, mean error of trajectory was 5.1 mm. The mean preoperative hematoma volume was 44.8 ml. The optimal trajectory angle averaged 39.5°and the length was 71 mm. Intraoperative blood loss was about 45 ml. Post-operative hematoma volume was 2.9 ml, and the average evacuation rate was 93.6%. One week after surgery, the mean GCS score was improved from 8.2 to 13.8 (p < 0.01). CONCLUSIONS: This simple, low-cost navigation method using 3D Slicer, an Android smartphone with the Compass APP, helps precisely insert the endoscopic working channel to the desired point, which is crucial for satisfactory evacuation of HBGH.

Isolated bilateral, large, basal ganglia haemorrhage following a traumatic brain injury: A case report.

Traumatic basal ganglia haemorrhage is rarely seen in clinical practice. Bilateral basal ganglia hematoma without any other cerebral lesions due to trauma is extremely uncommon and has been reported only in a few cases. Although the mechanisms of this condition are unclear, haemorrhagic contusions are thought to arise as a consequence of a shearing strain on cranial blood vessels due to high-velocity forces at the time of the injury. Here we describe a 63-year-old female patient with an isolated bilateral, large, basal ganglia haemorrhage secondary to a road traffic accident. The patient was promptly diagnosed and conservatively treated and had fully recovered after two months.

Different Effects of Hematoma Expansion on Short-Term Functional Outcome in Basal Ganglia and Thalamic Hemorrhages.

PURPOSE: To investigate the impact of hematoma expansion (HE) on short-term functional outcome of patients with thalamic and basal ganglia intracerebral hemorrhage. METHODS: Data of 420 patients with deep intracerebral hemorrhage (ICH) that received a baseline CT scan within 6 hours from symptom onset and a follow-up CT scan within 72 hours were retrospectively analyzed. The poor functional outcome was defined as modified Rankin score (mRS) > 3 at 30 days. Receiver operating characteristic (ROC) curves for relative and absolute growth of HE were generated and compared. Multivariable logistic regression models were used to analyze the impact of HE on the functional outcome in basal ganglia and thalamic hemorrhages. The predictive values for different thresholds of HE were calculated, and correlation coefficient matrices were used to explore the correlation between the covariables. RESULTS: Basal ganglia ICH showed a higher possibility of absolute hematoma growth than thalamic ICH. The area under the curve (AUC) for absolute and relative growth of thalamic hemorrhage was lower than that of basal ganglia hemorrhage (AUC 0.71 and 0.67, respectively) in discriminating short-term poor outcome with an AUC of 0.59 and 0.60, respectively. Each threshold of HE independently predicted poor outcome in basal ganglia ICH (P < 0.001), with HE > 3 ml and > 6 ml showing higher positive predictive values and accuracy compared to HE > 33%. In contrast, thalamic ICH had a smaller baseline volume (BV, 9.55 ± 6.85 ml) and was more likely to initially involve the posterior limb of internal capsule (PLIC) (85/153, 57.82%), and the risk of HE was lower without PLIC involvement (4.76%, P = 0.009). Therefore, in multivariate analysis, the effect of thalamic HE on poor prognosis was largely replaced by BV and the involvement of PLIC, and the adjusted odds ratios (ORs) of HE was not significant (P > 0.05). CONCLUSION: Though HE is a high-risk factor for short-term poor functional outcome, it is not an independent risk factor in thalamic ICH, and absolute growth is more predictive of poor outcome than relative growth for basal ganglia ICH.

Comparison of the curative effect and prognosis of stereotactic drainage and conservative treatment for moderate and small basal ganglia haemorrhage.

BACKGROUND: Minimally invasive surgery has achieved good results in the treatment of cerebral haemorrhage.However, no large-scale clinical study has demonstrated that surgical treatment of cerebral haemorrhages less than 30 ml can improve the curative effect. Our study explored the efficacy and complication of stereotactic drainage based on the amount of cerebral hemorrhage (15-30 ml) in hypertensive basal ganglia. METHOD: Sixty patients with hypertensive basal ganglia haemorrhages were divided into a control group and an experimental group with 30 patients in each group. Patients in the control group were treated conservatively. In contrast, those in the experimental group received stereotactic drainage, and urokinase was injected into the haematoma cavity after the operation. The haematoma volume at admission and 1, 3, 7 and 30 days after treatment and National Institute of Health stroke scale(NIHSS) score data were recorded. Complications after treatment in the two groups of data were compared and analysed. RESULT: No significant differences in age, sex, time of treatment after onset, admission blood pressure, admission haematoma volume or admission NIHSS score were noted between these two groups (P > 0.05). After treatment, significant differences in haematoma volume were noted between the two groups on the 1st, 3rd, 7th and 30th days after treatment (P < 0.05). The amount of hematoma of patients in the experimental group was significantly reduced compared with that in the control group, and the NIHSS scores were significantly different on the 3rd, 7th and 30th days after treatment. The neurological deficit scores of patients in the experimental group were significantly reduced compared with those in the control group, and the incidence of pulmonary infection and venous thrombosis in the lower limbs of patients in the experimental group were significantly reduced (P < 0.05). ROC curve analysis showed that stereotactic drainage affected the early neurological function of patients with small and medium basal ganglia haemorrhages. CONCLUSION: For patients with small and medium basal ganglia haemorrhages, stereotactic drainage can be used due to the faster drainage speed of haematomas after operation, which is beneficial to the recovery of neurological function and reduce complications.

The Hounsfield Unit of Perihematomal Edema Is Associated With Poor Clinical Outcomes in Intracerebral Hemorrhage.

BACKGROUND: Hounsfield unit (HU) of perihematomal edema (PHE) may be a predictor of prognosis of intracerebral hemorrhage (ICH). Our study evaluated whether PHE mean HU at the 72 hours after ICH predicts outcome, and how it compares against other PHE measures. METHODS: Patients with ICH from a tertiary medical institution were included. PHE was segmented by the semiautomatic plane method to measure volume and mean HU. Outcomes of interest was poor 90-day prognosis (modified Rankin Scale score ≥3). Logistic regression was used to assess relationships with outcome. RESULTS: Data from a total of 159 patients with ICH were collected. The median mean HU of PHE at 72 hours was 22.1 (IQR: 19.2-25.0). Binary logistic regression showed that the 72-hour PHE mean HU was negatively correlated with the poor prognosis of patients with ICH (OR 0.59, 95% CI 0.47-0.75, P < 0.05). The receiver operator curves of meaningful indicators revealed that the area under the curve (AUC) of PHE mean HU at 72 hours was larger and the difference of AUC between PHE mean HU with PHE absolute volume or extension distance were statistically significant (P < 0.05). The 72-hour PHE mean HU has a higher value in predicting adverse prognosis of patients with ICH. CONCLUSIONS: The PHE mean HU at 72 hours was negatively correlated with the poor prognosis of patients with ICH. The prediction ability of PHE mean HU at 72 hours was better than PHE absolute volume and extension distance, contributing to a rather good index for predicting outcome of ICH.

Bilateral basal ganglia bleed in traumatic brain injury: A case report.

Intracerebral haemorrhage can be classified into traumatic and non-traumatic. Traumatic Basal Ganglia Haemorrhage (TBGH) has been reported in 2.4-3% cases of all closed head injuries whereas the incidence is higher in postmortem studies (9.8%), nevertheless, a bilateral TBGH is an extremely rare entity. According to our search through literature, only 12 case reports of bilateral TBGH have been published previously. A simple bilateral TBGH is rarely seen without any other lesions as it is usually associated with skull fractures, haemorrhages or brainstem injuries, making its incidence more during autopsies. We present a 30-year old male patient who had a traumatic brain injury (TBI) secondary to Road Traffic Accident (RTA) with GCS of 12/15, having no other co-morbids. CT-scan revealed bilateral basal ganglia bleed and the patient improved on conservative management only.

Strictly Lobar Microbleeds Reflect Amyloid Angiopathy Regardless of Cerebral and Cerebellar Compartments.

BACKGROUND AND PURPOSE: We aimed to determine whether lobar cerebellar microbleeds or concomitant lobar cerebellar and deep microbleeds, in the presence of lobar cerebral microbleeds, attribute to underlying advanced cerebral amyloid angiopathy pathology or hypertensive arteriopathy. METHODS: We categorized 71 patients with suspected cerebral amyloid angiopathy markers (regardless of the presence of deep and cerebellar microbleeds) into 4 groups according to microbleed distribution: L (strictly lobar cerebral, n=33), L/LCbll (strictly lobar cerebral and strictly lobar cerebellar microbleeds, n=13), L/Cbll/D (lobar, cerebellar, and deep microbleeds, n=17), and L/D (lobar and deep, n=8). We additionally categorized patients with cerebellar microbleeds into 2 groups according to dentate nucleus involvement: strictly lobar cerebellar (n=16) and dentate (n=14). We then compared clinical characteristics, Aß (amyloid-ß) positivity on PET (positron emission tomography), magnetic resonance imaging cerebral amyloid angiopathy markers, and cerebral small vessel disease burden among groups. RESULTS: The frequency of Aß positivity was higher in the L and L/LCbll groups (81.8% and 84.6%) than in the L/Cbll/D and L/D groups (37.5% and 29.4%; P<0.001), while lacune numbers were lower in the L and L/LCbll groups (1.7±3.3 and 1.7±2.6) than in the L/Cbll/D and L/D groups (8.0±10.3 and 13.4±17.7, P=0.001). The L/LCbll group had more lobar cerebral microbleeds than the L group (93.2±121.8 versus 38.0±40.8, P=0.047). The lobar cerebellar group had a higher Aß positivity (75% versus 28.6%, P=0.011) and lower lacune number (2.3±3.7 versus 8.6±1.2, P=0.041) than the dentate group. CONCLUSIONS: Strictly lobar cerebral and cerebellar microbleeds are related to cerebral amyloid angiopathy, whereas any combination of concurrent lobar and deep microbleeds suggest hypertensive angiopathy regardless of cerebral or cerebellar compartments.

Evidence of motor injury due to damaged corticospinal tract following acute hemorrhage in the basal ganglia region.

The integrity of the corticospinal tract (CST) is significantly affected following basal ganglia haemorrhage. We aimed to assess the local features of CST and to effectively predict motor function by diffusion characteristics of CST in patients with motor injury following acute haemorrhage in the acute basal ganglia region. We recruited 37 patients with paresis of the lateral limbs caused by acute basal ganglia haemorrhage. Based on the automated fiber quantification method to track CST, assessed the character of each CST segment between the affected and contralateral sides, and correlated these with the Fugl-Meyer (FM) and Barthel Index (BI) scores at 6 months after onset. The fractional anisotropy (FA) values of the injured side of CST showed a significantly lower FA than the contralateral side along the tract profiles (p < 0.05, corrections for multiple comparisons). The FA values of each site at the internal capsule, closed corona radiata were positively correlated with the FM and BI score at 6 months after onset (p < 0.001, respectively). Our findings assessed the character of CST vividly in detail and dementated the primary sites of CST can predict the long-term outcome of motor function. This study may facilitate future clinical and cognitive studies of acute haemorrhage.

Bilateral Basal Ganglia Hemorrhage in a Patient with Confirmed COVID-19.

Bilateral basal ganglia hemorrhage is exceedingly rare. To our knowledge, our patient is the first reported case of a confirmed coronavirus disease 2019 (COVID-19) patient who had bilateral basal ganglia hemorrhage. In the absence of other risk factors for bilateral deep cerebral involvement, we suspect that COVID-19 may be contributing to these rare pathologies. Most published data represent a correlation between COVID-19 and neurologic complications, and more research is still needed to prove causation.

A Combined Approach to Intracerebral Hemorrhage: Intravenous Mesenchymal Stem Cell Therapy with Minimally Invasive Hematoma Evacuation.

BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent stromal cells currently being tested as therapy for a variety of diseases. MSC therapy and hematoma evacuation using a minimally invasive approach are being studied separately to improve clinical outcomes after stroke. We report the first case of a patient with intracerebral hemorrhage (ICH) treated with combination MSC therapy and endoscopic hematoma evacuation. CASE REPORT: A 36-year-old woman with a past medical history of essential chronic hypertension and right lung bronchial atresia presented to the emergency department with acute neurologic decline (National Institute of Health Stroke Scale [NIHSS] score, 22). Computed tomography showed a 4.4 × 3.5 × 3.5 cm right basal ganglia hemorrhage with intraventricular extension. An external ventricular drain was placed, and she was enrolled in a Phase I clinical trial investigating intravenous MSC therapy for acute ICH. Continued neurologic deterioration due to increased intracranial pressure led to minimally invasive hematoma evacuation using the Artemis Neuro Evacuation Device (Penumbra, Inc.) on hospital day 4. Follow-up scans showed decreased density and extent of hemorrhage. She was discharged on day 41 with improved neurologic function scores (NIHSS score, 2). At 3-month follow-up, she was walking on her own, but had residual left arm and hand weakness (modified Rankin Score, 2). CONCLUSIONS: This case report suggests that the combination of MSC therapy and minimally invasive hematoma evacuation may be safe and well tolerated. Further larger randomized clinical trials are required to identify whether MSC therapy in combination with minimally invasive hematoma evacuation is safe, tolerable, and potentially improves outcomes than either alone.