Effect of Baseline Antihypertensive Treatments on Stroke Severity and Outcomes in the BP TARGET Trial.

BACKGROUND: Acute ischemic stroke (AIS) patients with a history of hypertension experience worse outcomes, which may be explained by a deleterious impact of the renin-angiotensin system (RAS) overactivation. We sought to investigate whether prestroke antihypertensive treatments (AHT) influenced baseline stroke severity and neurological outcomes, in patients with AIS successfully treated by endovascular therapy. METHODS: We performed a post hoc analysis of the BP TARGET trial (Blood Pressure Target in Acute Stroke to Reduce Hemorrhage After Endovascular Therapy) and included hypertensive patients with available data regarding AHT at admission, categorized as RAS inhibitors (ACE [angiotensin-converting enzyme] inhibitors, ARBs [angiotensin 2 receptor blockers], and ß-blockers) and non-RAS inhibitors (calcium channel blockers and diuretics). Associations of each AHT with National Institutes of Health Stroke Scale (NIHSS) score at baseline were investigated in linear mixed model adjusted for the number of treatments and center. Associations of each AHT with 24-hour NIHSS change, intracranial hemorrhage were performed using linear mixed model adjusted for baseline NIHSS, the number of treatments, center, age, and sex and adjusted for age, sex, diabetes, and current smoking for favorable outcome. All analyses were performed on cases-available data regarding the low number of missing data. RESULTS: Overall, 203 patients with at least one AHT were included. Patients under non-RAS inhibitor treatments had a higher NIHSS score at baseline (adjusted mean difference=3.28 [95% CI, 1.33-5.22]; P=0.001). Conversely, patients under RAS inhibitor treatments had a lower baseline NIHSS score (adjusted mean difference=-2.81 [95% CI, -5.37 to -0.25]; P=0.031). Intracranial hemorrhage occurrence was significantly more frequent in patients under non-RAS inhibitor treatments (adjusted odds ratio of 2.48 [95% CI, 1.12-5.47]; P=0.025). Conversely, the use of RAS inhibitor treatments before AIS was not associated with higher odds of radiographic intracranial hemorrhage. Patients with non-RAS inhibitor treatments had less improvement of NIHSS at 24 hours compared with patients without (adjusted mean difference, 2.83 [95% CI, -0.16 to 5.81]; P=0.063). Baseline RAS inhibitor or noninhibitor treatments were not associated with favorable outcome. CONCLUSIONS: We showed an opposite effect of baseline AHT, based on their effect on the RAS. Patients treated with RAS inhibitor agents before AIS exhibited less severe AIS compared with patients under non-RAS inhibitor treatments, developed less intracranial hemorrhage at 24 hours and had a trend toward better NIHSS score at 24 hours. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03160677.

Association of Hypotension During Thrombectomy and Outcomes Differs With the Posterior Communicating Artery Patency.

BACKGROUND AND PURPOSE: Hypotension during endovascular therapy for acute ischemic stroke is associated with worse functional outcomes (FO). Given its important role in intracranial hemodynamics, we investigated whether hypotension during endovascular therapy had the same effect on FO according to the posterior communicating artery (PComA) patency. METHODS: We performed a post hoc analysis of the ASTER trial (Contact Aspiration Versus Stent Retriever for Successful Revascularization). Patients were included if they had middle cerebral artery occlusions. Primary outcome was favorable FO, defined by a modified Rankin Scale scores between 0 and 2 at 3 months. RESULTS: One hundred forty-eight patients with middle cerebral artery occlusion were included. In patients with no PComA, an increase in minimum mean arterial pressure was positively associated with favorable FO (odds ratio per 10 mm Hg increase, 1.59 [95%CI, 1.11-2.25]; P=0.010), whereas no association was found in patients with a PComA (odds ratio, 0.77 [95% CI, 0.54-1.08]; P=0.12). Patients with no PComA and longer cumulative time with mean arterial pressure <90 mm Hg or systolic blood pressure <140 mm Hg had significantly lower rates of favorable FO, with an odds ratio per 10-minute increase of 0.75 (95% CI, 0.59-0.94; P=0.010) and 0.74 (95% CI, 0.60-0.91; P=0.003), but not in patients with a PComA. CONCLUSIONS: Hypotension during endovascular therapy for middle cerebral artery occlusion is consistently associated with worse FO in patients with no PComA but not in those with a PComA. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02523261.

Local Anesthesia Without Sedation During Thrombectomy for Anterior Circulation Stroke Is Associated With Worse Outcome.

BACKGROUND AND PURPOSE: The best anesthetic management for mechanical thrombectomy of large vessel occlusion strokes is still uncertain and could impact the quality of reperfusion and clinical outcome. We aimed to compare the efficacy and safety outcomes between local anesthesia (LA) and conscious sedation in a large cohort of acute ischemic stroke patients with anterior circulation large vessel occlusion strokes treated with mechanical thrombectomy in current, everyday clinical practice. METHODS: Patients undergoing mechanical thrombectomy for anterior large vessel occlusion strokes at 4 comprehensive stroke centers in France between January 1, 2018, and December 31, 2018, were pooled from the ongoing prospective multicenter observational Endovascular Treatment in Ischemic Stroke Registry in France. Intention-to-treat and per-protocol analyses were used. RESULTS: Among the included 1034 patients, 762 were included in the conscious sedation group and 272 were included in the LA group. In the propensity score matched cohort, the rate of favorable outcome (90-day modified Rankin Scale score 0-2) was significantly lower in the LA group than in the conscious sedation group (40.0% versus 52.0%, matched relative risk=0.76 [95% CI, 0.60-0.97]), as well as the rate of successful reperfusion (modified Thrombolysis in Cerebral Infarction grade 2b-3; 76.6% versus 87.1%; matched relative risk=0.88 [95% CI, 0.79-0.98]). There was no difference in procedure time between the 2 groups. In the inverse probability of treatment weighting-propensity score-adjusted cohort, similar significant differences were found for favorable outcomes and successful reperfusion. In inverse probability of treatment weighting-propensity score-adjusted cohort, a higher rate of 90-day mortality and a lower parenchymal hematoma were observed after LA. The sensitivity analysis restricted to our per-protocol sample provided similar results in the matched- and inverse probability of treatment weighting-propensity cohorts. CONCLUSIONS: In the Endovascular Treatment in Ischemic Stroke registry mainly included patients in early time window (<6 hours), LA was associated with lower odds of favorable outcome, successful reperfusion, and higher odds of mortality compared with conscious sedation for mechanical thrombectomy of large vessel occlusion.

Contact Aspiration Versus Stent Retriever in Patients With Acute Ischemic Stroke With M2 Occlusion in the ASTER Randomized Trial (Contact Aspiration Versus Stent Retriever for Successful Revascularization).

BACKGROUND AND PURPOSE: Middle cerebral artery M2-segment occlusions represent an important subgroup of patients with acute stroke with large-vessel occlusion. The safety of mechanical thrombectomy, especially contact aspiration (CA), in such distal intracranial occlusions is still under debate. We compared reperfusion, adverse events, neurological recovery, and functional outcome of patients with isolated M2 occlusions according to the first-line strategy mechanical thrombectomy devices (CA versus stent retriever [SR]). METHODS: This is a post hoc analysis of the ASTER trial (Contact Aspiration Versus Stent Retriever for Successful Revascularization). The primary outcome was successful reperfusion at the end of all endovascular procedures, defined as modified Thrombolysis in Cerebral Infarction (mTICI) scores 2b/3. Secondary outcomes were mTICI 2c/3 and mTICI 3, 90-day functional outcome, assessed with the modified Rankin Scale score. Safety outcomes included 90-day mortality and any symptomatic intracerebral hemorrhage. RESULTS: Seventy-nine patients were included: 48 were allocated to the CA group and 31 to the SR group. There were no significant differences between CA and SR groups in reperfusion after all endovascular procedures regarding mTICI 2b/3 (89.6% versus 83.9%; P=0.36), mTICI 2c/3 (54.2% versus 54.8%; P=0.90), and mTICI 3 (35.4% versus 41.9%; P=0.36) rates. There were no significant differences between CA and SR groups in 90-day modified Rankin Scale ≤2 rate (54.4% versus 50.0%; P=0.84), 24-hour change in National Institutes of Health Stroke Scale (mean difference, -3.9; 95% confidence interval, -7.9 to 0.01), and Alberta Stroke Program Early Computed Tomography score (mean difference, 0.9; 95% confidence interval, -0.1 to 2.0) scores. Safety parameters were well balanced between the 2 groups except for a higher 90-day mortality rate in the CA group (19.6% versus 3.3%; P=0.078). CONCLUSIONS: First-line mechanical thrombectomy with CA compared with SR did not result in an increased successful revascularization rate in patients with acute stroke with isolated M2 occlusion.

Mechanical Thrombectomy Outcomes With or Without Intravenous Thrombolysis.

Background and Purpose- Intravenous thrombolysis (IVT) within 4.5 hours of symptom onset is currently recommended before mechanical thrombectomy (MT). We compared functional outcome, neurological recovery, reperfusion, and adverse events according to the use or not of IVT before MT. Methods- This is a post hoc analysis of the ASTER trial (Contact Aspiration Versus Stent Retriever for Successful Revascularization). The primary outcome was favorable 90-day functional outcome defined as a modified Rankin Scale of ≤2. Secondary outcomes were successful reperfusion following all procedures and after the first-line procedure, number of device passes, and change in National Institutes of Health Stroke Scale score at 24 hours. Safety outcomes included 90-day mortality and any symptomatic intracerebral hemorrhage. Results- Three hundred eighty-one patients were included, 250 of whom received IVT before MT (IVT+MT group). There were no significant differences between IVT+MT and MT-alone groups in 90-day favorable functional outcome, in successful reperfusion rate (modified Thrombolysis In Cerebral Infarction 2b or 3), in National Institutes of Health Stroke Scale score improvement at 24 hours, or in hemorrhagic complication rate. The 90-day mortality rate in the IVT+MT group was lower than after MT alone (fully-adjusted risk ratio, 0.59; 95% CI, 0.39-0.88). In a subgroup of patients without anticoagulant medication before stroke onset, we observed in the IVT+MT group a better functional outcome (fully-adjusted risk ratio, 1.38; 95% CI, 1.02-1.89), a higher successful recanalization rate after first-line strategy (fully-adjusted risk ratio, 1.26; 95% CI, 1.05-1.50), and a lower mortality rate (fully-adjusted risk ratio, 0.58; 95% CI, 0.36-0.93). Conclusions- Our results show that IVT+MT patients in the ASTER trial have lower 90-day mortality compared with those receiving MT alone. In a selected population of patients without prestroke anticoagulation, we demonstrated that IVT associated with MT might improve functional outcome and recanalization while reducing mortality rates.

Similar Outcomes for Contact Aspiration and Stent Retriever Use According to the Admission Clot Burden Score in ASTER.

BACKGROUND AND PURPOSE: The clot burden score (CBS) at admission reliably evaluates the thrombus burden in acute ischemic stroke patients with anterior circulation large vessel occlusion. Mechanical thrombectomy has been diversified, especially with contact aspiration technique, and its efficiency with respect to the thrombus burden is not known. We compared reperfusion, adverse events, neurological recovery, and 90-day functional outcome of stent retriever use versus contact aspiration according to the admission CBS. METHODS: This is a post hoc analysis of the ASTER (Contact Aspiration Versus Stent Retriever for Successful Revascularization) randomized trial. The primary outcome was successful reperfusion after all procedures, defined as modified Thrombolysis in Cerebral Infarction scores 2b/3. Secondary outcomes were 90-day functional outcome, assessed with the modified Rankin Scale. Safety outcomes included 90-day mortality and any intracerebral hemorrhage. RESULTS: A total of 231 randomized patients were included in this study: 114 patients had a CBS of 0 to 6 and 117 a CBS ≥7 at admission. Successful reperfusion at procedure end was achieved more frequently in patients with CBS ≥7 (88.9%) than patients with a CBS 0 to 6 (81.6%; fully adjusted risk ratio, 1.09; 95% confidence interval, 1.01-1.28). Favorable outcome (modified Rankin Scale score, 0-2) at 90 days was achieved in significantly more patients with CBS ≥7 (61.9%) than in patients with CBS 0 to 6 (41.8%; fully adjusted risk ratio, 1.19; 95% confidence interval, 1.02-1.40). No outcome differences of first-line mechanical thrombectomy strategy (aspiration versus stent) on any angiographic or clinical outcomes were observed between the 2 groups. We also found no evidence of interaction between first-line mechanical thrombectomy strategy and CBS groups regarding safety. CONCLUSIONS: First-line mechanical thrombectomy with contact aspiration compared with stent retriever did not result in an increased successful reperfusion rate in acute ischemic stroke patients with large vessel occlusion of the anterior circulation according to the admission CBS. The latter, however, seems to be a reliable prognostic indicator of angiographic and clinical outcome.

Predictors of favorable outcome after mechanical thrombectomy for anterior circulation acute ischemic stroke in octogenarians.

INTRODUCTION: Mechanical thrombectomy for anterior circulation large vessel occlusion (LVO) improves functional outcome at three months. This therapeutic approach is the new gold standard, with a benefit being also observed in elderly patients. However, data are limited in this heterogeneous and fragile population. The objectives of this study were, first, to describe outcome after mechanical thrombectomy in a representative group of patients over 80. Second, to evaluate factors associated with a favorable functional outcome after thrombectomy for anterior circulation LVO in elderly patients (aged≥80 years). METHODS: A total of 169 patients with anterior circulation LVO referred for an endovascular treatment were included. Primary outcome evaluated functional outcome at three months. Multivariable analysis was performed to identify prognostic factors in elderly patients with pre-stroke mRS≤3. RESULTS: Overall, 25.34% of patients (43/169) were functionally independent at three months (mRS≤2) and 16.57% (28/169) had a moderate functional disability (mRS=3). Mortality rate was 33.14% (56/169). At 24h, 7.1% of patients (12/169) had symptomatic hemorrhage. Male gender (P=0.033), low initial NIHSS (P=0.037), higher DWI-ASPECTS (P=0.022) and use of intravenous thrombolysis (IVT) (P=0.0193) were associated with a better functional outcome. CONCLUSIONS: There is no reason to withhold mechanical thrombectomy on the basis of age alone. Small infarct core, low NIHSS, male gender and use of IVT are associated with a better functional outcome.

Safety and efficacy of intensive systolic blood pressure lowering after successful endovascular therapy: a post hoc analysis of the BP TARGET trial.

BACKGROUND: The Safety and Efficacy of Intensive Blood Pressure Lowering after Successful Endovascular Therapy in Acute Ischaemic Stroke (BP TARGET) trial demonstrated no benefit from intensive systolic blood pressure (SBP) treatment after successful reperfusion with endovascular therapy. However, it remains unknown if the response to blood pressure treatment is modified by other factors. OBJECTIVE: To carry out a post hoc analysis of the BP TARGET trial data to determine if the response to blood pressure treatment is modified by factors such as age, history of hypertension, recanalization status, location of occlusion, diabetes, hyperglycemia, or pretreatment with intravenous thrombolysis. METHODS: This is a post hoc analysis of the BP TARGET trial. Patients were divided into groups based on age, diabetes, blood glucose, site of occlusion, history of hypertension, and pretreatment with intravenous thrombolysis. The primary outcome was any intraparenchymal hemorrhage. RESULTS: 318 patients were included. Diabetes modified the treatment effect on favorable functional outcome (Pheteogenity=0.041). There was a trend towards benefit from intensive SBP treatment in diabetic patients (OR=2.81; 95% CI 0.88 to 8.88; p=0.08) but not in non-diabetic patients (OR=0.75; 95% 0.45 to 126; p 0.28). Age, location of occlusion, admission SBP, pretreatment with intravenous thrombolysis, and history of hypertension did not modify the effect of intensive SBP treatment on any of the outcomes. CONCLUSION: The effect of SBP lowering treatment was not modified by age, location of occlusion history of hypertension, intravenous thrombolysis, and admission SBP. Diabetes modified the effect of intensive SBP lowering treatment, and there was a trend towards benefit from intensive SBP treatment in diabetic patients. This finding is hypothesis generating and requires further validation.

Endovascular therapy with or without intravenous thrombolysis in acute stroke with tandem occlusion.

BACKGROUND: Endovascular therapy (EVT) is effective and safe in patients with tandem occlusion. The benefit of intravenous thrombolysis (IVT) prior to EVT in acute tandem occlusion is debatable. OBJECTIVE: To compare EVT alone with EVT plus IVT in patients with acute ischemic stroke due to anterior circulation tandem occlusions. METHODS: This is an individual patient pooled analysis of the Thrombectomy In TANdem lesions (TITAN) and Endovascular Treatment in Ischemic Stroke (ETIS) Registries. Patients were divided into two groups based on prior IVT treatment: (1) IVT+ group, which included patients who received IVT prior to EVT, (2) IVT- group, which included patients who did not receive IVT prior to EVT. Propensity score (inverse probability of treatment weighting (IPTW)) was used to reduce baseline between-group differences. The primary outcome was favorable outcome-that is, modified Rankin Scale (mRS) score 0 to 2 at 90 days. RESULTS: Overall, 602 consecutive patients with an acute stroke with tandem occlusion were included (380 and 222 in the bridging therapy and EVT alone groups, respectively). Onset to imaging time was shorter in the IVT+ group (median 103 vs 140 min). In contrast, imaging to puncture time was longer in the IVT+ group (median 107 vs 91 min). In IPTW analysis, the IVT+ group had higher odds of favorable outcome, excellent outcome (90-day mRS score 0-1), and successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2b/3 at the end of EVT). There was no difference in the risk of significant hemorrhagic complications between groups. In secondary analysis of patients treated with acute cervical internal carotid artery stenting, bridging therapy was associated with higher odds of favorable outcome and lower odds of mortality at 90 days. CONCLUSIONS: Our results suggest that bridging therapy in patients with acute ischemic stroke due to anterior tandem occlusion is safe and may improve functional outcome, even in the setting of acute cervical internal carotid artery stenting during EVT.

Rescue carotid puncture for ischemic stroke treated by endovascular therapy: a multicentric analysis and systematic review.

BACKGROUND: Endovascular therapy (EVT) for acute ischemic stroke (AIS) can be challenging in older patients with supra-aortic tortuosity. Rescue carotid puncture (RCP) can be an alternative in case of supra-aortic catheterization failure by femoral access, but data regarding RCP are scarce. We sought to investigate the feasibility, effectiveness and safety of RCP for AIS treated by EVT. METHODS: Patients treated by EVT with RCP were included from January 2012 to December 2019 in the Endovascular Treatment in Ischemic Stroke (ETIS) multicentric registry. Main outcomes included reperfusion rates ( ≥ TICI2B), 3 month functional outcome (modified Rankin Scale) and 3 month mortality. We also performed an additional systematic review of the literature according to the PRISMA checklist to summarize previous studies on RCP. RESULTS: 25 patients treated by EVT with RCP were included from the ETIS registry. RCP mainly concerned elderly patients (median age 85 years, range 73-92) with supra-aortic tortuosity (n=16 (64%)). Intravenous thrombolysis (IVT) was used for nine patients (36%). Successful reperfusion was achieved in 64%, 87.5% of patients were dependent at 3 months, and 3 month mortality was 45.8%. The systematic review yielded comparable results. In pooled individual data, there was a shift toward better functional outcome in patients with successful reperfusion (median (IQR) 4 (2-6) vs 6 (4-6), p=0.011). CONCLUSION: RCP mainly concerned elderly patients admitted for AIS with anterior LVO with supra-aortic tortuosity. The procedure seemed feasible, notably for patients treated with IVT, and led to significant reperfusion rates at the end of procedure, but with pronounced unfavorable outcomes at 3 months. RCP should be performed under general anesthesia to avoid life-threatening complications and ensure airways safety. Finally, RCP led to low rates of closure complications, emphasizing that this concern should not withhold RCP, if indicated.

Safety and efficacy of intensive blood pressure lowering after successful endovascular therapy in acute ischaemic stroke (BP-TARGET): a multicentre, open-label, randomised controlled trial.

BACKGROUND: High systolic blood pressure after successful endovascular therapy for acute ischaemic stroke is associated with increased risk of intraparenchymal haemorrhage. However, no randomised controlled trials are available to guide optimal management. We therefore aimed to assess whether an intensive systolic blood pressure target resulted in reduced rates of intraparenchymal haemorrhage compared with a standard systolic blood pressure target. METHODS: We did a multicentre, open-label, randomised controlled trial at four academic hospital centres in France. Eligible individuals were adults (aged ≥18 years) with an acute ischaemic stroke due to a large-vessel occlusion that was successfully treated with endovascular therapy. Patients were randomly assigned (1:1) to either an intensive systolic blood pressure target group (100-129 mm Hg) or a standard care systolic blood pressure target group (130-185 mm Hg), by means of a central web-based procedure, stratified by centre and intravenous thrombolysis use before endovascular therapy. In both groups, the target systolic blood pressure had to be achieved within 1 h after randomisation and maintained for 24 h with intravenous blood pressure lowering treatments. The primary outcome was the rate of radiographic intraparenchymal haemorrhage at 24-36 h and the primary safety outcome was the occurrence of hypotension. Analyses were done on an intention-to-treat basis. BP-TARGET is registered with ClinicalTrials.gov, number NCT03160677, and the trial is closed at all participating sites. FINDINGS: Between June 21, 2017, and Sept 27, 2019, 324 patients were enrolled in the four participating stroke centres: 162 patients were randomly assigned to the intensive target group and 162 to the standard target group. Four (2%) of 162 patients were excluded from the intensive target group and two (1%) of 162 from the standard target group for withdrawal of consent or legal reasons. The mean systolic blood pressure during the first 24 h after reperfusion was 128 mm Hg (SD 11) in the intensive target group and 138 mm Hg (17) in the standard target group. The primary outcome was observed in 65 (42%) of 154 patients in the intensive target group and 68 (43%) of 157 in the standard target group on brain CT within 24-36 h after reperfusion] (adjusted odds ratio 0·96, 95% CI 0·60-1·51; p=0·84). Hypotensive events were not significantly different between both groups and occurred in 12 (8%) of 158 patients in the intensive target and five (3%) of 160 in the standard target group. Mortality within the first week after randomisation occurred in 11 (7%) of 158 patients in the intensive target group and in seven (4%) of 160 in the standard target group. INTERPRETATION: An intensive systolic blood pressure target of 100-129 mm Hg after successful endovascular therapy did not reduce radiographic intraparenchymal haemorrhage rates at 24-36 h as compared with a standard care systolic blood pressure target of 130-185 mm Hg. Notably, these results are applicable to patients with successful reperfusion and systolic blood pressures of more than 130 mm Hg at the end of procedure. Further studies are needed to understand the association between blood pressure and outcomes after reperfusion. FUNDING: French Health Ministry.

Recent advances in devices for mechanical thrombectomy.

INTRODUCTION: Acute ischemic stroke (AIS) secondary to the occlusion of a large intracranial vessel (LVO) is a recognized public health problem. Mechanical thrombectomy (MT) has gained full acceptance: Class A, Level 1 in 2015 after the publication of numerous trials. Further meta-analyses have scrutinized extensively those results and international recommendations and guidelines have been given. Nevertheless, multiple-specific points remain to be clarified and are or will be under investigations. AREAS COVERED: This review of the most recent literature (mostly publications after 2015) will cover the actual common practice for MT, especially focusing on the devices available (and their validation), how they are commonly used, relate the most relevant results, and detail some emerging technologies. EXPERT OPINION: The authors will express their own view on the current practice and emphasize on the areas where questions remain and hypothesize what specific improvements are necessary and prone to occur.

Direct aspiration stroke thrombectomy: a comprehensive review.

Mechanical thrombectomy is now the standard of care for acute ischemic stroke patients with large vessel occlusions, and can be performed with several devices and techniques. One of these techniques, direct aspiration (DA), consists of navigating a large-bore catheter up to the face of the clot and initiating forceful suction. This comprehensive review has three objectives: (1) to describe the direct aspiration technique; (2) to present the available evidence regarding predictive factors of DA success and performance compared with other techniques; and (3) to discuss the forthcoming improvements in distal aspiration.

Transvenous embolization of a carotid cavernous fistula complicated by a hematoma at the tentorial edge.

Indirect (dural) carotid cavernous fistulae are generally treated by endovascular surgery primary transvenous embolization that is safe and effective. We describe here a case of a left indirect carotid cavernous fistula that presented with proptosis and eye redness. The patient underwent transvenous embolization of carotid cavernous sinus. The procedure was complicated by a haemorrhage from the cavernous sinus. The post procedural CT scan showed a haematoma at the tentorial edge. Precise diagnosis and prompt treatment could prevent severe complications.