Institutional trends over a decade in catheter-directed interventions for pulmonary embolism.

OBJECTIVE: Catheter-directed interventions (CDIs) are commonly performed for acute pulmonary embolism (PE). The evolving catheter types and treatment algorithms impact the use and outcomes of these interventions. This study aimed to investigate the changes in CDI practice and their impact on outcomes. METHODS: Patients who underwent CDIs for PE between 2010 and 2019 at a single institution were identified from a prospectively maintained database. A PE team was launched in 2012, and in 2014 was established as an official Pulmonary Embolism Response Team. CDI annual use trends and clinical failures were recorded. Clinical success was defined as physiologic improvement in the absence of major bleeding, perioperative stroke or other procedure-related adverse event, decompensation for submassive or persistent shock for massive PE, the need for surgical thromboembolectomy, or death. Major bleeding was defined as requiring a blood transfusion, a surgical intervention, or suffering from an intracranial hemorrhage. RESULTS: There were 372 patients who underwent a CDI for acute PE during the study period with a mean age of 58.9 ± 15.4 years; there were males 187 (50.3%) and 340 patients has a submassive PE (91.4%). CDI showed a steep increase in the early Pulmonary Embolism Response Team years, peaking in 2016 with a subsequent decrease. Ultrasound-assisted thrombolysis was the predominant CDI technique peaking at 84% of all CDI in 2014. Suction thrombectomy use peaked at 15.2% of CDI in 2019. The mean alteplase dose with catheter thrombolysis techniques decreased from 26.8 ± 12.5 mg in 2013 to 13.9 ± 7.5 mg in 2019 (P < .001). The mean lysis time decreased from 17.2 ± 8.3 hours in 2013 to 11.3 ± 8.2 hours in 2019 (P < .001). Clinical success for the massive and the submassive PE cohorts was 58.1% and 91.2%, respectively; the major bleed rates were 25.0% and 5.3%. There were two major clinical success peaks, one in 2015 mirroring our technical learning curve and one in 2019 mirroring our patient selection learning curve. The clinical success decrease in 2018 was primarily derived from blood transfusions owing to acute blood loss during suction thrombectomy. CONCLUSIONS: CDIs for acute PE have rapidly evolved with high success rates. Multidisciplinary approaches among centers with appropriate expertise are advisable for the safe and successful implementation of catheter interventions.

Reflection on the Past, Present, and Future of Thrombolytic Therapy for Acute Ischemic Stroke.

More than 25 years have passed since the US Food and Drug Administration approved IV recombinant tissue plasminogen activator (alteplase) for the treatment of acute ischemic stroke. This landmark decision brought a previously untreatable disease into a new therapeutic landscape, providing inspiration for clinicians and hope to patients. Since that time, the use of alteplase in the clinical setting has become standard of care, continually improving with quality measures such as door-to-needle times and other metrics of specialized stroke unit care. The past decade has seen more widespread use of alteplase in the prehospital setting with mobile stroke units and telestroke and beyond initial time windows via the use of CT perfusion or MRI. Simultaneously, the position of alteplase is being challenged by new lytics and by the concept of its bypass altogether in the era of endovascular therapy. We provide an overview of alteplase, including its earliest trials and how they have shaped the current therapeutic landscape of ischemic stroke treatment, and touch on new frontiers for thrombolytic therapy. We highlight the critical role of thrombolytic therapy in the past, present, and future of ischemic stroke care.

Advanced management of intermediate-high risk pulmonary embolism.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .

National Trends in Telestroke Utilization in a US Commercial Platform Prior to the COVID-19 Pandemic.

OBJECTIVES: Most data on telestroke utilization come from single academic hub-and-spoke telestroke networks. Our objective was to describe characteristics of telestroke consultations among a national sample of telestroke sites on one of the most commonly used common vendor platforms, prior to the COVID-19 public health emergency. MATERIALS AND METHODS: A commercial telestroke vendor provided data on all telestroke consultations by two specialist provider groups from 2013-2019. Kendall's τ ß nonparametric test was utilized to assess time trends. Generalized linear models were used to assess the association between hospital consult utilization and alteplase use adjusting for hospital characteristics. RESULTS: Among 67,736 telestroke consultations to 132 spoke sites over the study period, most occurred in the emergency department (90%) and for stroke indications (final clinical diagnoses: TIA 13%, ischemic stroke 39%, hemorrhagic stroke 2%, stroke mimics 46%). Stroke severity was low (median NIHSS 2, IQR 0-6). Alteplase was recommended for 23% of ischemic stroke patients. From 2013 to 2019, times from ED arrival to NIHSS, CT scan, imaging review, consult, and alteplase administration all decreased (p<0.05 for all), while times from consult start to alteplase recommendation and bolus increased (p<0.01 for both). Transfer was recommended for 8% of ischemic stroke patients. Number of patients treated with alteplase per hospital increased with increasing number of consults and hospital size and was also associated with US region in unadjusted and adjusted analyses. Longer duration of hospital participation in the network was associated with shorter hospital median door-to-needle time for alteplase delivery (39 min shorter per year, p=0.04). CONCLUSIONS: Among spoke sites using a commercial telestroke platform over a seven-year time horizon, times to consult start and alteplase bolus decreased over time. Similar to academic networks, duration of telestroke participation in this commercial network was associated with faster alteplase delivery, suggesting practice improves performance.

Changes in Stroke Hospital Care During the COVID-19 Pandemic: A Systematic Review and Meta-Analysis.

[Figure: see text].

Ischemic Stroke in Patients With Pulmonary Arteriovenous Fistulas.

BACKGROUND AND PURPOSE: Pulmonary arteriovenous fistulas (PAVFs) are a treatable cause of acute ischemic stroke (AIS), not mentioned in current American Heart/Stroke Association guidelines. PAVFs are recognized as an important complication of hereditary hemorrhagic telangiectasia. METHODS: The prevalence of PAVF and hereditary hemorrhagic telangiectasia among patients admitted with AIS in the United States (2005-2014) was retrospectively studied, utilizing the Nationwide Inpatient Sample database. Clinical factors, morbidity, mortality, and management were compared in AIS patients with and without PAVF/hereditary hemorrhagic telangiectasia. RESULTS: Of 4 271 910 patients admitted with AIS, 822 (0.02%) were diagnosed with PAVF. Among them, 106 of 822 (12.9%) were diagnosed with hereditary hemorrhagic telangiectasia. The prevalence of PAVF per million AIS admissions rose from 197 in 2005 to 368 in 2014 (Ptrend, 0.026). Patients with PAVF were younger than AIS patients without PAVF (median age, 57.5 versus 72.5 years), had lower age-adjusted inpatient morbidity (defined as any discharge other than home; 39.6% versus 46.9%), and had lower in-hospital case fatality rates (1.8% versus 5.1%). Multivariate analyses identified the following as independent risk markers (odds ratio [95% CI]) for AIS in patients with PAVF: hypoxemia (8.4 [6.3-11.2]), pulmonary hemorrhage (7.9 [4.1-15.1]), pulmonary hypertension (4.3 [4.1-15.1]), patent foramen ovale (4.2 [3.5-5.1]), epistaxis (3.7 [2.1-6.8]), venous thrombosis (2.6 [1.9-3.6]), and iron deficiency anemia (2 [1.5-2.7]). Patients with and without PAVF received intravenous thrombolytics at a similar rate (5.9% versus 5.8%), but those with PAVF did not receive mechanical thrombectomy (0% versus 0.7%). CONCLUSIONS: Pulmonary arteriovenous fistula-related ischemic stroke represents an important younger demographic with a unique set of stroke risk markers, including treatable conditions such as causal PAVFs and iron deficiency anemia.

Dynamic Neutrophil-Lymphocyte Ratios Predict Short-term Prognostic Outcome of Thrombolysis in Patients with Acute Ischemic Stroke.

AIM: The main purpose of this study was to investigate the dynamic changes of neutrophils-lymphocytes ratios (NLRs) in patients with acute ischemic stroke (AIS) and their relationships with 3-month prognostic outcomes. METHODS: Two hundred ninety-one patients with AIS were included in this study, followed up for 3 months. At admission, 1 and 7 days after recombinant tissue plasminogen activator (r-tPA) injection, blood samples were obtained. Outcome events included excellent outcome, good outcome, and death defined as modified Rankin Scale (mRS) scores of 0-1, 0-2, and 6 respectively. RESULTS: NLRs measured in admission and 7 days after r-tPA treatment were associated with prognosis outcome after 3 months. Twenty-four-hour NLR is an excellent indicator in forecasting (excellent outcome's the areas under the curve (AUC) = 0.725; good outcome AUC = 0.742; death AUC = 0.759). In addition, we were surprised to find that dynamic increase in NLR within 24 h is significantly related to excellent and good outcomes. CONCLUSIONS: Twenty-four-hour NLR is related to the severity of AIS and poor prognosis, which can help early risk stratification. SIGNIFICANCE: We can predict the prognosis of AIS more accurately. Compared with previous studies, our study has shown the dynamic changes of NLR and its relationship with NIHSS and multiple prognostic.

Pulmonary Embolism Response Team utilization during the COVID-19 pandemic.

Coronavirus disease 2019 (COVID-19) may predispose patients to venous thromboembolism (VTE). Limited data are available on the utilization of the Pulmonary Embolism Response Team (PERT) in the setting of the COVID-19 global pandemic. We performed a single-center study to evaluate treatment, mortality, and bleeding outcomes in patients who received PERT consultations in March and April 2020, compared to historical controls from the same period in 2019. Clinical data were abstracted from the electronic medical record. The primary study endpoints were inpatient mortality and GUSTO moderate-to-severe bleeding. The frequency of PERT utilization was nearly threefold higher during March and April 2020 (n = 74) compared to the same period in 2019 (n = 26). During the COVID-19 pandemic, there was significantly less PERT-guided invasive treatment (5.5% vs 23.1%, p = 0.02) with a numerical but not statistically significant trend toward an increase in the use of systemic fibrinolytic therapy (13.5% vs 3.9%, p = 0.3). There were nonsignificant trends toward higher in-hospital mortality or moderate-to-severe bleeding in patients receiving PERT consultations during the COVID-19 period compared to historical controls (mortality 14.9% vs 3.9%, p = 0.18 and moderate-to-severe bleeding 35.1% vs 19.2%, p = 0.13). In conclusion, PERT utilization was nearly threefold higher during the COVID-19 pandemic than during the historical control period. Among patients evaluated by PERT, in-hospital mortality or moderate-to-severe bleeding were not significantly different, despite being numerically higher, while invasive therapy was utilized less frequently during the COVID-19 pandemic.

Patient Characteristics and Outcomes Associated with Decline in Stroke Volumes During the Early COVID-19 Pandemic.

BACKGROUND AND PURPOSE: Delayed evaluation of stroke may contribute to COVID-19 pandemic-related morbidity and mortality. This study evaluated patient characteristics, process measures and outcomes associated with the decline in stroke presentation during the early pandemic. METHODS: Volumes of stroke presentations, intravenous thrombolytic administrations, and mechanical thrombectomies from 52 hospitals from January 1-June 30, 2020 were analyzed with piecewise linear regression and linear spline models. Univariate analysis compared pandemic (case) and pre-pandemic (control) groups defined in relation to the nadir of daily strokes during the study period. Significantly different patient characteristics were further evaluated with logistic regression, and significantly different process measures and outcomes were re-analyzed after propensity score matching. RESULTS: Analysis of 7,389 patients found daily stroke volumes decreased 0.91/day from March 12-26 (p < 0.0001), reaching a nadir 35.0% less than expected, and increased 0.15 strokes/day from March 27-June 23, 2020 (p < 0.0001). Intravenous thrombolytic administrations decreased 3.3/week from February 19-March 31 (p = 0.0023), reaching a nadir 33.4% less than expected, and increased 1.4 administrations/week from April 1-June 23 (p < 0.0001). Mechanical thrombectomy volumes decreased by 1.5/week from February 19-March 31, 2020 (p = 0.0039), reaching a nadir 11.3% less than expected. The pandemic group was more likely to ambulate independently at baseline (p = 0.02, OR = 1.60, 95% CI = 1.08-2.42), and less likely to present with mild stroke symptoms (NIH Stroke Scale ≤ 5; p = 0.04, OR = 1.01, 95% CI = 1.00-1.02). Process measures and outcomes of each group did not differ, including door-to-needle time, door-to-puncture time, and successful mechanical thrombectomy rate. CONCLUSION: Stroke presentations and acute interventions decreased during the early COVID-19 pandemic, at least in part due to patients with lower baseline functional status and milder symptoms not seeking medical care. Public health messaging and initiatives should target these populations.

A meta-analysis of the global impact of the COVID-19 pandemic on stroke care & the Houston Experience.

OBJECTIVE: To review the global impact of the COVID-19 pandemic on stroke care-metrics and report data from a health system in Houston. METHODS: We performed a meta-analysis of the published literature reporting stroke admissions, intracerebral hemorrhage (ICH) cases, number of thrombolysis (tPA) and thrombectomy (MT) cases, and time metrics (door to needle, DTN; and door to groin time, DTG) during the pandemic compared to prepandemic period. Within our hospital system, between January-June 2019 and January-June 2020, we compared the proportion of stroke admissions and door to tPA and MT times. RESULTS: A total of 32,640 stroke admissions from 29 studies were assessed. Compared to prepandemic period, the mean ratio of stroke admissions during the pandemic was 70.78% [95% CI, 65.02%, 76.54%], ICH cases was 83.10% [95% CI, 71.01%, 95.17%], tPA cases was 81.74% [95% CI, 72.33%, 91.16%], and MT cases was 88.63% [95% CI, 74.12%, 103.13%], whereas DTN time was 104.48% [95% CI, 95.52%, 113.44%] and DTG was 104.30% [95% CI, 81.99%, 126.61%]. In Houston, a total of 4808 cases were assessed. There was an initial drop of ~30% in cases at the pandemic onset. Compared to 2019, there was a significant reduction in mild strokes (NIHSS 1-5) [N (%), 891 (43) vs 635 (40), P = 0.02]. There were similar mean (SD) (mins) DTN [44 (17) vs 42 (17), P = 0.14] but significantly prolonged DTG times [94 (15) vs 85 (20), P = 0.005] in 2020. INTERPRETATION: The COVID-19 pandemic led to a global reduction in stroke admissions and treatment interventions and prolonged treatment time metrics.

The association of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, and lymphocyte to monocyte ratio with post-thrombolysis early neurological outcomes in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: To investigate the association of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) with post-thrombolysis early neurological outcomes including early neurological improvement (ENI) and early neurological deterioration (END) in patients with acute ischemic stroke (AIS). METHODS: AIS patients undergoing intravenous thrombolysis were enrolled from April 2016 to September 2019. Blood cell counts were sampled before thrombolysis. Post-thrombolysis END was defined as the National Institutes of Health Stroke Scale (NIHSS) score increase of ≥ 4 within 24 h after thrombolysis. Post-thrombolysis ENI was defined as NIHSS score decrease of ≥ 4 or complete recovery within 24 h. Multinomial logistic regression analysis was performed to explore the relationship of NLR, PLR, and LMR to post-thrombolysis END and ENI. We also used receiver operating characteristic curve analysis to assess the discriminative ability of three ratios in predicting END and ENI. RESULTS: Among 1060 recruited patients, a total of 193 (18.2%) were diagnosed with END and 398 (37.5%) were diagnosed with ENI. Multinomial logistic model indicated that NLR (odds ratio [OR], 1.385; 95% confidence interval [CI] 1.238-1.551, P = 0.001), PLR (OR, 1.013; 95% CI 1.009-1.016, P = 0.001), and LMR (OR, 0.680; 95% CI 0.560-0.825, P = 0.001) were independent factors for post-thrombolysis END. Moreover, NLR (OR, 0.713; 95% CI 0.643-0.791, P = 0.001) served as an independent factor for post-thrombolysis ENI. Area under curve (AUC) of NLR, PLR, and LMR to discriminate END were 0.763, 0.703, and 0.551, respectively. AUC of NLR, PLR, and LMR to discriminate ENI were 0.695, 0.530, and 0.547, respectively. CONCLUSIONS: NLR, PLR, and LMR were associated with post-thrombolysis END. NLR and PLR may predict post-thrombolysis END. NLR was related to post-thrombolysis ENI.

Prediction of Early Neurological Deterioration in Individuals With Minor Stroke and Large Vessel Occlusion Intended for Intravenous Thrombolysis Alone.

Importance: The best reperfusion strategy in patients with acute minor stroke and large vessel occlusion (LVO) is unknown. Accurately predicting early neurological deterioration of presumed ischemic origin (ENDi) following intravenous thrombolysis (IVT) in this population may help to select candidates for immediate transfer for additional thrombectomy. Objective: To develop and validate an easily applicable predictive score of ENDi following IVT in patients with minor stroke and LVO. Design, Setting, and Participants: This multicentric retrospective cohort included 729 consecutive patients with minor stroke (National Institutes of Health Stroke Scale [NIHSS] score of 5 or less) and LVO (basilar artery, internal carotid artery, first [M1] or second [M2] segment of middle cerebral artery) intended for IVT alone in 45 French stroke centers, ie, including those who eventually received rescue thrombectomy because of ENDi. For external validation, another cohort of 347 patients with similar inclusion criteria was collected from 9 additional centers. Data were collected from January 2018 to September 2019. Main Outcomes and Measures: ENDi, defined as 4 or more points' deterioration on NIHSS score within the first 24 hours without parenchymal hemorrhage on follow-up imaging or another identified cause. Results: Of the 729 patients in the derivation cohort, 335 (46.0%) were male, and the mean (SD) age was 70 (15) years; of the 347 patients in the validation cohort, 190 (54.8%) were male, and the mean (SD) age was 69 (15) years. In the derivation cohort, the median (interquartile range) NIHSS score was 3 (1-4), and the occlusion site was the internal carotid artery in 97 patients (13.3%), M1 in 207 (28.4%), M2 in 395 (54.2%), and basilar artery in 30 (4.1%). ENDi occurred in 88 patients (12.1%; 95% CI, 9.7-14.4) and was strongly associated with poorer 3-month outcomes, even in patients who underwent rescue thrombectomy. In multivariable analysis, a more proximal occlusion site and a longer thrombus were independently associated with ENDi. A 4-point score derived from these variables-1 point for thrombus length and 3 points for occlusion site-showed good discriminative power for ENDi (C statistic = 0.76; 95% CI, 0.70-0.82) and was successfully validated in the validation cohort (ENDi rate, 11.0% [38 of 347]; C statistic = 0.78; 95% CI, 0.70-0.86). In both cohorts, ENDi probability was approximately 3%, 7%, 20%, and 35% for scores of 0, 1, 2 and 3 to 4, respectively. Conclusions and Relevance: The substantial ENDi rates observed in these cohorts highlights the current debate regarding whether to directly transfer patients with IVT-treated minor stroke and LVO for additional thrombectomy. Based on the strong associations observed, an easily applicable score for ENDi risk prediction that may assist decision-making was derived and externally validated.

Early Impact of the COVID-19 Pandemic on Acute Stroke Treatment Delays.

This is an observational cohort study comparing 156 patients evaluated for acute stroke between March 30 and May 31, 2020 at a comprehensive stroke center with 138 patients evaluated during the corresponding time period in 2019. During the pandemic, the proportion of COVID-19 positive patients was low (3%), the time from symptom onset to hospital presentation was significantly longer, and a smaller proportion of patients underwent reperfusion therapy. Among patients directly evaluated at our institution, door-to-needle and door-to-recanalization metrics were significantly longer. Our findings support concerns that the current pandemic may have a negative impact on the management of acute stroke.

An Update on the Management of Budd-Chiari Syndrome.

Budd-Chiari syndrome (BCS) is an uncommon condition, caused by obstruction to hepatic venous outflow. It is largely underdiagnosed, and a high index of suspicion is required for any patient with unexplained portal hypertension. The understanding of its etiology and pathology is improving with advances in diagnostic techniques. Recent studies reported an identifiable etiology in > 80% of cases. Myeloproliferative neoplasm (MPN) is the most common etiology, and genetic studies help in diagnosing latent MPN. Better cross-sectional imaging helps delineate the site of obstruction accurately. The majority of BCS patients are now treated by endovascular intervention and anticoagulation which have improved survival in this disease. Angioplasty of hepatic veins/inferior vena cava remains under-utilized at present. While surgical porto-systemic shunts are no longer done for BCS, liver transplantation is reserved for select indications. Some of the unresolved issues in the current management of BCS are also discussed in this review.

Variants of WNT7A and GPR124 are associated with hemorrhagic transformation following intravenous thrombolysis in ischemic stroke.

AIMS: The canonical Wnt signaling pathway plays an essential role in blood-brain barrier integrity and intracerebral hemorrhage in preclinical stroke models. Here, we sought to explore the association between canonical Wnt signaling and hemorrhagic transformation (HT) following intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients as well as to determine the underlying cellular mechanisms. METHODS: 355 consecutive AIS patients receiving IVT were included. Blood samples were collected on admission, and HT was detected at 24 hours after IVT. 117 single-nucleotide polymorphisms (SNPs) of 28 Wnt signaling genes and exon sequences of 4 core cerebrovascular Wnt signaling components (GPR124, RECK, FZD4, and CTNNB1) were determined using a customized sequencing chip. The impact of identified genetic variants was further studied in HEK 293T cells using cellular and biochemical assays. RESULTS: During the study period, 80 patients experienced HT with 27 parenchymal hematoma (PH). Compared to the non-PH patients, WNT7A SNPs (rs2163910, P = .001, OR 2.727; rs1124480, P = .002, OR 2.404) and GPR124 SNPs (rs61738775, P = .012, OR 4.883; rs146016051, P < .001, OR 7.607; rs75336000, P = .044, OR 2.503) were selectively enriched in the PH patients. Interestingly, a missense variant of GPR124 (rs75336000, c.3587G>A) identified in the PH patients resulted in a single amino acid alteration (p.Cys1196Tyr) in the intracellular domain of GPR124. This variant substantially reduced the activity of WNT7B-induced canonical Wnt signaling by decreasing the ability of GPR124 to recruit cytoplasmic DVL1 to the cellular membrane. CONCLUSION: Variants of WNT7A and GPR124 are associated with increased risk of PH in patients with AIS after intravenous thrombolysis, likely through regulating the activity of canonical Wnt signaling.