High Rate of Passenger Lymphocyte Syndrome after ABO Minor Incompatible Lung Transplantation.

Rationale: Passenger lymphocyte syndrome (PLS) may complicate minor ABO mismatched lung transplantation (LuTX) via donor-derived red cell antibody-induced hemolysis.Objectives: To ascertain the incidence and specificity of PLS-relevant antibodies among the study population as well as the dynamics of hemolysis parameters and the transfusion requirement of patients with or without PLS.Methods: In this cohort study, 1,011 patients who received LuTX between January 2010 and June 2019 were studied retrospectively. Prospectively, 87 LuTX (July 2019 to June 2021) were analyzed. Postoperative ABO antibody and hemolytic marker determinations, transfusion requirement, and duration of postoperative hospital care were analyzed. Retrospectively, blood group A recipients of O grafts with PLS were compared with those without.Measurements and Main Results: PLS affected 18.18% (retrospective) and 30.77% (prospective) of A recipients receiving O grafts, 5.13% of B recipients of O grafts, and 20% of AB patients receiving O transplants. Anti-A and anti-A1 were the predominant PLS-inducing antibodies, followed by anti-B and anti-A,B. Significantly lower hemoglobin values (median, 7.4 vs. 8.3 g/dl; P = 0.0063) and an approximately twice as high percentage of patients requiring blood transfusions were seen in PLS. No significant differences in other laboratory markers, duration of hospital stay, or other complications after LuTX were registered.Conclusions: Minor ABO incompatible LuTX recipients are at considerable risk of developing clinically significant PLS. Post-transplant monitoring combining red cell serology and hemolysis marker determination appears advisable so as not to overlook hemolytic episodes that necessitate antigen-negative transfusion therapy.

Prehospital identification of acute ischaemic stroke with large vessel occlusion: a retrospective study from western Norway.

BACKGROUND: In 2019, the emergency medical services (EMS) covering the western Norway Regional Health Authority area implemented its version of the prehospital clinical criteria G-FAST (Gaze deviation, Facial palsy, Arm weakness, Visual loss, Speech disturbance) to detect acute ischaemic stroke (AIS) with large vessel occlusion (LVO). For patients with gaze deviation and at least one other G-FAST symptom, a primary stroke centre (PSC) may be bypassed and the patient taken directly to a comprehensive stroke centre (CSC) for rapid endovascular treatment (EVT) evaluation. The study aim was to investigate the efficacy of the G-FAST criteria for LVO patient selection and direct transfer to a CSC. METHODS: This retrospective study included patients with code-red emergency medical communication centre (EMCC) stroke suspicion ambulance dispatch between August to December 2020. Stroke suspicion was defined as having at least one G-FAST symptom at EMS arrival. We obtained patient data from dispatches from EMCCs, EMS records and local EVT registries. Clinical features, CT images, and reperfusion treatment were recorded. The test characteristics for gaze deviation plus one other G-FAST symptom in detecting LVO were determined. RESULTS: Among 643 patients, 59 were diagnosed with LVO at hospital arrival. In this group, seven fulfilled the G-FAST criteria for direct transport to a CSC at EMS arrival on scene, resulting in a sensitivity of 12% (95% CI 5% to 23%). The specificity was 99.66% (95% CI 98.77% to 99.96%), the positive predictive value 78%, and the negative predictive value 92%. EVT was performed in 64% (38/59) of LVO cases. Median time from PSC arrival to start of EVT at a CSC was 163 min. CONCLUSION: The use of local G-FAST prehospital criteria by EMS personnel to identify patients with AIS with LVO is not suitable for selection of patients with LVO for direct transfer to a CSC.

Biomarkers predictive of atrial fibrillation in patients with cryptogenic stroke. Insights from the Nordic Atrial Fibrillation and Stroke (NOR-FIB) study.

BACKGROUND AND PURPOSE: There are currently no biomarkers to select cryptogenic stroke (CS) patients for monitoring with insertable cardiac monitors (ICMs), the most effective tool for diagnosing atrial fibrillation (AF) in CS. The purpose of this study was to assess clinically available biomarkers as predictors of AF. METHODS: Eligible CS and cryptogenic transient ischaemic attack patients underwent 12-month monitoring with ICMs, clinical follow-up and biomarker sampling. Levels of cardiac and thromboembolic biomarkers, taken within 14 days from symptom onset, were compared between patients diagnosed with AF (n = 74) during monitoring and those without AF (n = 185). Receiver operating characteristic curves were created. Biomarkers reaching area under the receiver operating characteristic curve ≥ 0.7 were dichotomized by finding optimal cut-off values and were used in logistic regression establishing their predictive value for increased risk of AF in unadjusted and adjusted models. RESULTS: B-type natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), creatine kinase, D-dimer and high-sensitivity cardiac troponin I and T were significantly higher in the AF than non-AF group. BNP and NT-proBNP reached the predefined area under the curve level, 0.755 and 0.725 respectively. Optimal cut-off values were 33.5 ng/l for BNP and 87 ng/l for NT-proBNP. Regression analysis showed that NT-proBNP was a predictor of AF in both unadjusted (odds ratio 7.72, 95% confidence interval 3.16-18.87) and age- and sex-adjusted models (odds ratio 4.82, 95% confidence interval 1.79-12.96). CONCLUSION: Several clinically established biomarkers were associated with AF. NT-proBNP performed best as AF predictor and could be used for selecting patients for long-term monitoring with ICMs.

Thrombectomy in large vessel occlusion stroke-Does age matter?

OBJECTIVES: Endovascular treatment (EVT) is the gold standard treatment for emergent large vessel occlusion (LVO). The benefit of EVT for emergent LVO in elderly patients (>80 years old) is still debated as they have been under-represented in randomized controlled trials. Elderly patients with an emergent LVO are a growing population warranting further study. MATERIALS & METHODS: We included 225 consecutive patients treated with EVT for LVO either in the anterior or posterior circulation. The clinical outcome was assessed using the National Institute of Health Stroke Scale (NIHSS). Long-term functional outcome was assessed using 90-day modified ranking scale (mRS). RESULTS: Neurological improvement: A five-year higher age predicted a 0.43 higher mean NIHSS score after EVT (p = .027). After adjusting for confounders (influencing variables), the association between age and post-interventional NIHSS was reduced and non-significant (p = .17). At discharge, a five-year higher age predicted a 0.74 higher mean NIHSS (p = .003). After adjusting for confounders this association was reduced and non-significant (p = .06). Long-term functional outcome: A five-year higher age predicted a 0.20 higher mRS at three months (p < .001). When adjusting for confounders this number was reduced to 0.16, yet still highly significant (p < .001). CONCLUSIONS: Age seems to have a minor role in predicting neurological improvement after EVT but has an impact on long-term functional outcome. The decision to perform or withhold EVT should therefore not solely be based on age.

Brain monitoring in hospitals needs to be strengthened. / Hjerneovervåking i sykehusene må styrkes.

Careful brain monitoring saves lives and is beneficial to patients' health. Nevertheless, Norway lacks guidelines for brain monitoring in hospitals.

Improving Stroke Care in Times of the COVID-19 Pandemic Through Simulation: Practice Your Protocols!

During the coronavirus disease 2019 (COVID-19) pandemic, infectious disease control is of utmost importance in acute stroke treatment. This is a new situation for most stroke teams that often leads to uncertainty among physicians, nurses, and technicians who are in immediate contact with patients. The situation is made even more complicated by numerous new regulations and protocols that are released in rapid succession. Herein, we are describing our experience with simulation training for COVID-19 stroke treatment protocols. One week of simulation training allowed us to identify numerous latent safety threats and to adjust our institution-specific protocols to mitigate them. It also helped our physicians and nurses to practice relevant tasks and behavioral patterns (eg, proper donning and doffing PPE, where to dispose potentially contaminated equipment) to minimize their infectious exposure and to adapt to the new situation. We therefore strongly encourage other hospitals to adopt simulation training to prepare their medical teams for code strokes during the COVID-19 pandemic.

Endovascular thrombectomy at low-volume centres: A Bayesian solution.

PURPOSE: Endovascular treatment (EVT) is traditionally performed by neurointerventional radiologists at tertiary medical centres imposing long transport ways to large vessel occlusion (LVO) stroke patients in rural areas. The purpose of this study is to evaluate the technical and clinical results over time at Stavanger University Hospital, a hospital without neurointerventional expertise, where trained general interventional radiologist performs EVT. METHODS: All patients with LVO stroke treated with EVT from May 2009 to December 2018 were included in the analysis. Technical outcome was measured by the modified treatment in cerebral ischaemia (mTICI) score, functional outcome by the modified Rankin Scale (mRS), complications registered. RESULTS: A total of 235 patients were treated with EVT. An angiographically good result (mTICI 2b or 3) could be seen in 66.7% of the patients treated the first year. In 2011, the year EVT with stent retrievers was introduced, the recanalization rate rose to 81.8%, and from 2014 onwards, it was stable around 80%. After introduction of aspiration together with stent retrievers in 2012, a good functional outcome (mRS 0-2) was obtained in >40% of the treated patients. In 2018, 61.1% of the patients got a good functional outcome. CONCLUSIONS: Endovascular treatment of LVO stroke performed by general vascular interventional radiologist in close collaboration with diagnostic neuroradiologists and stroke neurologists can achieve technical revascularization results and clinical patient outcomes in line with international recommendations, and the randomized controlled studies performed. This approach may help to introduce EVT in geographical areas where this service is lacking due to the absence of neurointerventional specialists.

Clinical outcomes and safety profile of Tenecteplase in wake-up stroke.

BACKGROUND: Tenecteplase has probably pharmacological and clinical advantages in the treatment of acute ischemic stroke. There are lacking data about safety and efficacy of tenecteplase in wake-up stroke (WUPS). AIMS: To investigate safety and efficacy of tenecteplase compared to alteplase in WUPS patients included in NOR-TEST. METHODS: WUPS patients in NOR-TEST were included in the study based on DWI-FLAIR mismatch. Included patients randomly assigned (1:1) to receive intravenous tenecteplase 0.4 mg/kg (to a maximum of 40 mg) or alteplase 0.9 mg/kg (to a maximum of 90 mg). Neurological improvement was defined as 1) favorable functional outcome at 90 days modified Rankin Scale (mRS) of 0 or 1 and 2) neurological improvement measured with the National Institutes of Health Stroke Scale (NIHSS) of 4 points within 24 hours as compared to admission NIHSS or NIHSS 0 at 24 hours. RESULTS: Of 1100 patients from 13 stroke centers included in NOR-TEST, 45 were WUPS patients. Of these, 5 patients were stroke mimics and excluded. Of the remaining 40 patients (3.6%), 24 were treated with alteplase (60%). There was no difference in the number of patients achieving a good clinical outcome (mRS 0-1) in either treatment group. Patients treated with tenecteplase showed a better early neurological improvement (87.5% vs 54.2%, P = 0.027). No ICH was detected on MRI/CT 24-28 hours after thrombolysis. CONCLUSIONS: In WUPS patients treated in NOR-TEST, there was no difference in clinical outcomes at 90 days and no ICH events or deaths were observed in either alteplase- or tenecteplase-treated patients. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique identifier: NCT01949948.

Safety and Outcomes of Tenecteplase in Moderate and Severe Ischemic Stroke.

Background and Purpose- Tenecteplase represents a promising alternative to alteplase as thrombolytic treatment in acute ischemic stroke. There are limited data on tenecteplase 0.4 mg/kg in patients with increased stroke severity. We aimed to assess safety and efficacy of tenecteplase 0.4 mg/kg in patients with moderate and severe ischemic stroke. Methods- NOR-TEST (Norwegian Tenecteplase Stroke Trial) was a phase III trial designed to investigate the safety and efficacy of tenecteplase 0.4 mg/kg versus alteplase 0.9 mg/kg in ischemic stroke. In this post hoc analysis, moderate stroke was defined as admission National Institutes of Health Stroke Scale; 6 to 14 and severe stroke as National Institutes of Health Stroke Scale; ≥15. Rates of favorable outcome at 90 days, symptomatic intracerebral hemorrhage (sICH), and mortality after 7 and 90 days were assessed. Results- In patients with moderate stroke (n=261), there were no differences in rates of favorable outcome, sICH, or mortality between tenecteplase and alteplase. In patients with severe stroke (n=87), there were no differences in outcome, frequency of sICH, or mortality at 7 days, but all-cause mortality at 90 days was increased in patients treated with tenecteplase (10 [26.3%] versus 4 [9.1%]; P=0.045). One patient died of sICH in the tenecteplase group, and 2 patients died of sICH in the alteplase group. Conclusions- Rates of favorable outcome and sICH were similar between treatment groups in patients with moderate and severe stroke. Mortality after 90 days was increased in patients with severe stroke receiving tenecteplase. Future studies assessing tenecteplase 0.4 mg/kg should monitor safety parameters closely in patients with severe stroke. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01949948.

Endovascular Thrombectomy in the Elderly: Do Radiological and Clinical Outcomes Differ from Those in Younger Patients? A Prospective Single-Center Experience.

OBJECTIVES: Endovascular treatment (EVT) has emerged as the gold standard therapy for stroke due to large vessel occlusion (LVO). There is however limited evidence to suggest that similar efficacy can be expected in elderly patients. We aimed to assess the efficacy and safety of EVT in elderly patients (aged > 80), comparing outcomes to younger patients (aged < 80). MATERIAL AND METHODS: A total of 195 patients with LVO stroke treated with EVT were included and dichotomized by age. We compared neurological improvement, clinical 90 day outcome, technical recanalization rates, procedure-related complications, and mortality in between the groups. RESULTS: Both groups showed equally marked neurological improvement. A favorable outcome modified Rankin Scale (mRS < 2) was seen in 28% of the elderly patients compared to 46% of the younger patients (p = 0.01). mRS 0-3 was seen in 46% of the elderly patients and 58% of the younger patients (p = 0.09). The rates of successful technical recanalization did not differ between the groups and there were no differences in procedural complication rates or incidence of symptomatic intracranial bleeding. Three-month mortality rates were however higher in the elderly group. CONCLUSIONS: EVT in the elderly resulted in equally notable neurological improvement as compared to younger patients. Although the elderly had a higher mortality rate and fewer favorable clinical outcomes at 3 month follow-up, a strict upper age limit for EVT seems unjustified.

Risk factors for early bleeding complications after lung transplantation - a retrospective cohort study.

Risk factors for early bleeding complications after lung transplantation are not well described. Our aim was to evaluate coagulation test results and the use of extracorporeal membrane oxygenation as risk factors for bleeding after lung transplantation. We analyzed a single-center cohort of bilateral lung transplants between January 2009 and August 2015. Predictors of severe postoperative bleeding (bleeding requiring reoperation within 48 h of transplantation) were assessed using multivariable logistic regression. The effect of bleeding on survival was assessed using a Cox proportional-hazards model. Twenty-nine (4.5%) of 641 patients experienced severe postoperative bleeding. Postoperative fibrinogen levels (OR = 0.99, 95% CI 0.98-0.995, P = 0.001; per mg/dl increase) and pre- and postoperative use of extracorporeal membrane oxygenation (OR = 14.41% 95% CI 5.4-40.19, P < 0.001 and OR = 4.25, 95% CI 1.0-11.09, P = 0.002, respectively) were associated with an increased risk of severe postoperative bleeding. Severe postoperative bleeding was associated with decreased survival within 60 days after transplantation (adjusted HR = 5.73, 95% CI 2.52-13.02, P < 0.001). Low postoperative fibrinogen levels, and pre- and postoperative use of extracorporeal membrane oxygenation were risk factors for bleeding after lung transplantation.

Monitoring following acute stroke should be improved. / Overvåkning etter akutt hjerneslag bør bli bedre.

Many serious complications following acute stroke can be prevented and treated. This requires close and systematic monitoring following stroke.

Mass Media Intervention in Western Norway Aimed at Improving Public Recognition of Stroke, Emergency Response, and Acute Treatment.

BACKGROUND: This study evaluates the effect of a mass media intervention (MMI) on the number of admissions to the emergency room (ER) with a suspected acute-onset stroke and on the number of patients treated with intravenous thrombolysis (IVT). The MMI was run for 1 month, with a precampaign month, priming the treatment chain and raising in-hospital awareness. METHODS: This study conducted a prospective analysis of all patients admitted to the ER before, during, and after the MMI to assess changes in admission rate and IVT treatment rate. The primary end point was to assess any change in the IVT treatment rate, and the secondary end point was to determine the number of acute stroke admissions to the ER within 4.5 hours of symptom onset. RESULTS: The MMI resulted in an increased IVT treatment rate from 7.3 to 11.3 patients per month, an increment of 54% (P = .002). This also resulted in IVT treatment percentages as high as 42%. The number of suspected acute stroke admissions to the ER increased from 37.3 to 72.8 patients per month, a 97% increase (P < .0001). The Epinion interviews showed that stroke symptom recognition increased from 66% to 75%. CONCLUSION: The MMI produced a significant increase in IVT treatment rate. This increased treatment rate is largely due to the increase in the number of acute stroke admissions to the ER. Targeting the treatment chain before the MMI led to unprecedented IVT treatment percentages. The effect of our MMI lasted for approximately 6 months before tapering off; repeated campaigns are a prerequisite for sustained IVT treatment rates.

Long-Term Mortality and Its Risk Factors in Stroke Survivors.

BACKGROUND: Stroke is one of the leading causes of mortality worldwide. Understanding the risk factors associated with stroke mortality is important to improve patient management. Few studies have examined long-term mortality and its associated predictive risk factors. METHODS: We examined long-term mortality in 1137 patients with acute stroke and compared it to a geographically age- and sex-matched, stroke-free control group. We followed the stroke patients for as long as 16.4 years. In 1018 of these patients we assessed the effect of demographic, clinical, and hematological factors on mortality. RESULTS: At the end of the study period, 51.7% of the patients and 32.7% of the stroke-free control individuals had died (hazard ratio 2.2, confidence interval 1.9-2.5, P < .001). A total of 72.5% of the patients and 53% of the controls with 12 years' follow-up (n = 570) had died (P < .001). Regression analyses indicate that, in addition to known risk factors such as age, diabetes, and stroke severity, both low cholesterol (P < .001) and hemoglobin (P < .002), hyperhomocysteinemia (P = .005), and elevated serum creatinine (P < .001) at index stroke are associated with increased long-term mortality. CONCLUSIONS: Stroke patients surviving the first year after stroke have a markedly increased mortality rate as seen in long-term follow-up. Furthermore, the results from this study indicate that changes in creatinine, homocysteine, and hemoglobin should be followed more carefully as standard practice after acute stroke.

The Norwegian tenecteplase stroke trial (NOR-TEST): randomised controlled trial of tenecteplase vs. alteplase in acute ischaemic stroke.

BACKGROUND: Alteplase is the only approved thrombolytic agent for acute ischaemic stroke. The overall benefit from alteplase is substantial, but some evidence indicates that alteplase also has negative effects on the ischaemic brain. Tenecteplase may be more effective and less harmfull than alteplase, but large randomised controlled phase 3 trials are lacking. The Norwegian Tenecteplase Stroke Trial (NOR-TEST) aims to compare efficacy and safety of tenecteplase vs. alteplase. METHODS/DESIGN: NOR-TEST is a multi-centre PROBE (prospective randomised, open-label, blinded endpoint) trial designed to establish superiority of tenecteplase 0.4 mg/kg (single bolus) as compared with alteplase 0.9 mg/kg (10% bolus + 90% infusion/60 minutes) for consecutively admitted patients with acute ischaemic stroke eligible for thrombolytic therapy, i.e. patients a) admitted <4½ hours after symptoms onset; b) admitted <4½ hours after awakening with stroke symptoms c) receiving bridging therapy before embolectomy.Randomisation tenecteplase:alteplase is 1:1. The primary study endpoint is favourable functional outcome defined as modified Rankin Scale 0-1 at 90 days. Secondary study endpoints are: 1) haemorrhagic transformation (haemorrhagic infarct/haematoma); 2) symptomatic cerebral haemorrhage on CT 24-48 hours; 3) major neurological improvement at 24 hours; 4) recanalisation at 24-36 hours; 5) death. DISCUSSION: NOR-TEST may establish a novel approach to acute ischaemic stroke treatment. A positive result will lead to a more effective, safer and easier treatment for all acute ischaemic stroke pasients.NOR-TEST is reviewed and approved by the Regional Committee for Medical and Health Research Ethics (2011/2435), and The Norwegian Medicines Agency (12/01402). NOR-TEST is registered with EudraCT No 2011-005793-33 and in ClinicalTrials.gov (NCT01949948).

Cerebrospinal fluid Aß levels correlate with structural brain changes in Parkinson's disease.

ParkWest is a large Norwegian multicenter study of newly diagnosed drug-naïve subjects with Parkinson's disease (PD). Cognitively normal PD subjects (PDCN) and PD subjects with mild cognitive impairment (PDMCI) from this cohort have significant hippocampal atrophy and ventricular enlargement, compared to normal controls. Here, we aimed to investigate whether the same structural changes are associated with cerebrospinal fluid (CSF) levels of amyloid beta (Aß)38 , Aß40 , Aß42 , total tau (t-tau), and phosphorylated tau (p-tau). We performed three-dimensional radial distance analyses of the hippocampi and lateral ventricles using the MRI data from ParkWest subjects who provided CSF at baseline. Our sample consisted of 73 PDCN and 18 PDMCI subjects. We found significant associations between levels of all three CSF Aß analytes and t-tau and lateral ventricular enlargement in the pooled sample. In the PDCN sample, all three amyloid analytes showed significant associations with the radial distance of the occipital and frontal horns of the lateral ventricles. CSF Aß38 and Aß42 showed negative associations, with enlargement in occipital and frontal horns of the lateral ventricles in the pooled sample, and a negative association with the occipital horns in PDMCI. CSF Aß levels in early PD correlate with ventricular enlargement, previously associated with PD dementia. Therefore, CSF and MRI markers may help identify PD patients at high risk for developing cognitive decline and dementia in the course of their illness. Contrary to Alzheimer's disease, we found no associations between CSF t-tau and p-tau and hippocampal atrophy.