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.

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.

Atrial fibrillation in cryptogenic stroke and transient ischaemic attack - The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study: Rationale and design.

PURPOSE: Paroxysmal atrial fibrillation is often suspected as a probable cause of cryptogenic stroke. Continuous long-term ECG monitoring using insertable cardiac monitors is a clinically effective technique to screen for atrial fibrillation and superior to conventional follow-up in cryptogenic stroke. However, more studies are needed to identify factors which can help selecting patients with the highest possibility of detecting atrial fibrillation with prolonged rhythm monitoring. The clinical relevance of short-term atrial fibrillation, the need for medical intervention and the evaluation as to whether intervention results in improved clinical outcomes should be assessed. METHOD: The Nordic Atrial Fibrillation and Stroke Study is an international, multicentre, prospective, observational trial evaluating the occurrence of occult atrial fibrillation in cryptogenic stroke and transient ischaemic attack. Patients with cryptogenic stroke or transient ischaemic attack from the Nordic countries are included and will have the Reveal LINQ® Insertable cardiac monitor system implanted for 12 months for atrial fibrillation detection. Biomarkers which can be used as predictors for atrial fibrillation and may identify patients, who could derive the most clinical benefit from the detection of atrial fibrillation by prolonged monitoring, are being studied. CONCLUSION: The primary endpoint is atrial fibrillation burden within 12 months of continuous rhythm monitoring. Secondary endpoints are atrial fibrillation burden within six months, levels of biomarkers predicting atrial fibrillation, CHA2DS2-VASc score, incidence of recurrent stroke or transient ischaemic attack, use of anticoagulation and antiarrhythmic drugs, and quality of life measurements. The clinical follow-up period is 12 months. The study started in 2017 and the completion is expected at the end of 2020.

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.

Achillea Wilhelmsii C. KochHydroalcoholic Extract Induces Apoptosis and Alters LIN28B and p53 Gene Expression in Hela Cervical Cancer Cells.

BACKGROUND: Inappropriate activation of the proto-oncogene LIN28B and inactivation of the p53 tumor suppressor, have been shown to have a critical role in tumorigenesis. Previous research has shown therapeutic potential for the use of herbal plants as an alternative strategy for cancer treatment. Achillae wilhelmsii C. Koch is a plant that has been traditionally used for its medicinal properties. The aim of this study was to investigate the cytotoxic and apoptosis-inducing effect of Achillea wilhelmsii C. Koch hydroalcoholic extract (AWHE) on HeLa cervical cancer cells and its effect on LIN28B and p53 expression. METHODS: The cytotoxic activity of AWHE was evaluated on HeLa cells using a trypan blue exclusion assay. The Annexin V/PI double staining assay was used to evaluate the apoptosis-inducing effect of the extract. The expression of LIN28B and p53 mRNA was measured using the real-time-PCR method. RESULTS: Treatment with AWHE was shown to induce cytotoxicity in both time and concentration-dependent manners (P<0.05). The proposition of HeLa cells undergoing apoptosis increased with increasing concentrations of AWHE (P<0.05). The mRNA levels of p53 increased following 12, 24, and 48 hours of AWHE treatment whereas the mRNA levels of LIN28B were significantly decreased after 4 to 12 hours of AWHE treatment (p<0.05). CONCLUSION: Our findings confirmed the pro-apoptotic function of AWHE on the cervical cancer HeLa cell line. This indicates that targeting the LIN28B signaling cascade may be a promising therapeutic strategy for cervical cancer. Further research is required to understand the therapeutic effects of AWHE in primary human cervical cancer cells and a pre-clinical cervical cancer model.

Outcome of pediatric renal transplantation in Labfi Nejad Hospital, Tehran, Iran.

Kidney transplantation is the treatment of choice for children with end-stage renal disease. In Iran, a kidney transplantation program was started in the Labfi Nejad Hospital, Tehran in 1985. From 1985 to 2003, 278 children (mean age 11.6 years, 59.7% males) received their first renal transplant. All transplants were donations from live donors (12.5% live-related donors); 30.8% of patients were preemptively transplanted. The overall 1-year patient survival rate was 92% and the 5-year survival rate 74%. The median graft survival time was 7.2 years. The rate of graft survival was 88.8% at 1 year, 77% at 3 years, 67% at 5 years, 50% at 7 years, and 43% at 10 years after transplantation. The survival rate of patients and transplants improved significantly with time (p<0.05). In patients transplanted before 1997, the 5-year graft survival was 50% and 82% in patients transplanted after 1997. At the same time intervals, the frequency of acute rejection episodes was 66.6 versus 40.8% and of chronic rejection 50.5 versus 28.7%. The outcome in children below the age of 6 years was poor. Graft survival was negatively correlated with the frequency and an early time point of acute rejection episodes. The modus of transplantation (preemptive or postdialysis) did not influence the results. In conclusion, patient and graft survival in transplanted children significantly improved with time, thus reflecting greater medical and surgical experience, new immunosuppressive drugs, and better compliance.

Determination of endocrine disrupting compounds in marine water by nanoliquid chromatography/direct-electron ionization mass spectrometry.

We present a new method for the determination of 29 endocrine-disrupting compounds in marine water. This method is based on a solid-phase extraction preconcentration technique, followed by a nanoscale liquid chromatography/direct-electron ionization (EI) mass spectrometric analysis. Direct-EI is a novel technique for the rapid conversion of a GC/MS into an efficient and reliable LC/MS for EI detection. The capability to acquire EI mass spectra of the analytes, and to operate in selected ion monitoring mode during real sample analyses, allows certain identification and precise quantification. In addition, this method is not influenced by the polarity of the analytes and does not require different detection modes (positive and negative) for identification with API techniques. Limits of detection of the method span from 0.4 to 118.7 ng.L(-1), corresponding to an instrumental detection limit of 0.005-1.260 ng. Linear regression and recovery experiment data, together with their standard deviations, are also presented. Marine water samples were collected along the middle-western Adriatic Coast (Italy), near the shore and at the mouth of rivers and canals.