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Neurofilament Light Chain Protein Is a Predictive Biomarker for Stroke After Surgical Repair for Acute Type A Aortic Dissection.

ABSTRACT: Background: Although great progress has been made in surgery and perioperative care, stroke is still a fatal complication of acute type A aortic dissection (ATAAD). Serum biomarkers may help assess brain damage and predict patient's prognosis. Methods: From March, 2019 to January, 2020, a total of 88 patients underwent surgical treatment at the Department of Cardiovascular Surgery of Beijing Anzhen Hospital, China, and were enrolled in this study. Patients were divided into two groups according to whether they had suffered a stroke after the operation. Blood samples were collected at 8 time points within 3 days after surgery to determine the level of S100β, neuron-specific enolase (NSE) and neurofilament light chain protein (NFL). Receiver operating characteristic curves (ROC) were established to explore the biomarker predictive value in stroke. The area under the curve (AUC) was used to quantify the ROC curve. Results: The patient average age was 48.1 ± 11.0 years old and 70 (79.6%) patients were male. Fifteen (17.0%) patients suffered stroke after surgery. The NFL levels of patients in the stroke group at 12 and 24 h after surgery were significantly higher than those in the non-stroke group (all P < 0.001). However, the NSE and S100β levels did not differ significantly at any time point between the two groups. The predictive value of NFL was the highest at 12 and 24 h after surgery, and the AUC was 0.834 (95% CI, 0.723-0.951, P < 0.001) and 0.748 (95% CI, 0.603-0.894, P = 0.004), respectively. Its sensitivity and specificity at 12 h were 86.7 and 71.6%, respectively. The NFL cutoff value for the diagnosis of stroke at 12 h after surgery was 16.042 ng/ml. Conclusions: This study suggests that NFL is an early and sensitive serum marker for predicting post-operative neurological prognosis of ATAAD patients. Further studies, including large-scale prospective clinical trials, are necessary to test whether the NFL can be used as a biomarker for clinical decision-making.

SUBMITTER: Zhang K

PROVIDER: S-EPMC8631920 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveTo identify changes in the proteome associated with onset and progression of hereditary transthyretin-mediated (hATTR) amyloidosis, also known as ATTRv amyloidosis, we performed an observational, case-controlled study that compared proteomes of patients with ATTRv amyloidosis and healthy controls.MethodsPlasma levels of >1,000 proteins were measured in patients with ATTRv amyloidosis with polyneuropathy who received either placebo or patisiran in a Phase 3 study of patisiran (APOLLO), and in healthy controls. The effect of patisiran on the time profile of each protein was determined by linear mixed model at 0, 9, and 18 months. Neurofilament light chain (NfL) was further assessed with an orthogonal quantitative approach.ResultsLevels of 66 proteins were significantly changed with patisiran vs placebo, with NfL change most significant (p < 10-20). Analysis of changes in protein levels demonstrated that the proteome of patients treated with patisiran trended toward that of healthy controls at 18 months. Healthy controls' NfL levels were 4-fold lower than in patients with ATTRv amyloidosis with polyneuropathy (16.3 pg/mL vs 69.4 pg/mL, effect -53.1 pg/mL [95% confidence interval -60.5 to -45.9]). NfL levels at 18 months increased with placebo (99.5 pg/mL vs 63.2 pg/mL, effect 36.3 pg/mL [16.5-56.1]) and decreased with patisiran treatment (48.8 pg/mL vs 72.1 pg/mL, effect -23.3 pg/mL [-33.4 to -13.1]) from baseline. At 18 months, improvement in modified Neuropathy Impairment Score +7 score after patisiran treatment significantly correlated with reduced NfL (R = 0.43 [0.29-0.55]).ConclusionsFindings suggest that NfL may serve as a biomarker of nerve damage and polyneuropathy in ATTRv amyloidosis, enable earlier diagnosis of patients with ATTRv amyloidosis, and facilitate monitoring of disease progression.Classification of evidenceThis study provides Class III evidence that NfL levels may enable earlier diagnosis of polyneuropathy in patients with ATTRv amyloidosis and facilitate monitoring of disease progression.

Project description:Background Neurofilament light chain (NfL) in cerebrospinal fluid (CSF) is a biomarker of multiple sclerosis (MS). However, CSF sampling is invasive and has limited the clinical application. With the development of highly sensitive single-molecule assay, the accurate quantification of the very low NfL levels in blood become feasible. As evidence being accumulated, we performed a meta-analysis to evaluate the diagnostic and predictive value of blood NfL in MS patients. Methods We performed literature search on PubMed, EMBASE, Web of Science and Cochrane Library from inception to May 31, 2022. The blood NfL differences between MS vs. controls, MS vs. clinically isolated syndrome (CIS), progressive MS (PMS) vs. relapsing-remitting MS (RRMS), and MS in relapse vs. MS in remission were estimated by standard mean difference (SMD) and corresponding 95% confidence interval (CI). Pooled hazard ratio (HR) and 95%CI were calculated to predict time to reach Expanded Disability Status Scale (EDSS) score≥4.0 and to relapse. Results A total of 28 studies comprising 6545 MS patients and 2477 controls were eligible for meta-analysis of diagnosis value, and 5 studies with 4444 patients were synthesized in analysis of predictive value. Blood NfL levels were significantly higher in MS patients vs. age-matched controls (SMD = 0.64, 95%CI 0.44–0.85, P<0.001), vs. non-matched controls (SMD = 0.76, 95%CI 0.56–0.96, P<0.001) and vs. CIS patients (SMD = 0.30, 95%CI 0.18–0.42, P<0.001), in PMS vs. RRMS (SMD = 0.56, 95%CI 0.27–0.85, P<0.001), and in relapsed patients vs. remitted patients (SMD = 0.54, 95%CI 0.16–0.92, P = 0.005). Patients with high blood NfL levels had shorter time to reach EDSS score≥4.0 (HR = 2.36, 95%CI 1.32–4.21, P = 0.004) but similar time to relapse (HR = 1.32, 95%CI 0.90–1.93, P = 0.155) compared to those with low NfL levels. Conclusion As far as we know, this is the first meta-analysis evaluating the diagnosis and predictive value of blood NfL in MS. The present study indicates blood NfL may be a useful biomarker in diagnosing MS, distinguishing MS subtypes and predicting disease worsening in the future.

Project description:Aims/hypothesisNo established blood-based biomarker exists to monitor diabetic sensorimotor polyneuropathy (DSPN) and evaluate treatment response. The neurofilament light chain (NFL), a blood biomarker of neuroaxonal damage in several neurodegenerative diseases, represents a potential biomarker for DSPN. We hypothesised that higher serum NFL levels are associated with prevalent DSPN and nerve dysfunction in individuals recently diagnosed with diabetes.MethodsThis cross-sectional study included 423 adults with type 1 and type 2 diabetes and known diabetes duration of less than 1 year from the prospective observational German Diabetes Study cohort. NFL was measured in serum samples of fasting participants in a multiplex approach using proximity extension assay technology. DSPN was assessed by neurological examination, nerve conduction studies and quantitative sensory testing. Associations of serum NFL with DSPN (defined according to the Toronto Consensus criteria) were estimated using Poisson regression, while multivariable linear and quantile regression models were used to assess associations with nerve function measures. In exploratory analyses, other biomarkers in the multiplex panel were also analysed similarly to NFL.ResultsDSPN was found in 16% of the study sample. Serum NFL levels increased with age. After adjustment for age, sex, waist circumference, height, HbA1c, known diabetes duration, diabetes type, cholesterol, eGFR, hypertension, CVD, use of lipid-lowering drugs and use of non-steroidal anti-inflammatory drugs, higher serum NFL levels were associated with DSPN (RR [95% CI] per 1-normalised protein expression increase, 1.92 [1.50, 2.45], p<0.0001), slower motor (all p<0.0001) and sensory (all p≤0.03) nerve conduction velocities, lower sural sensory nerve action potential (p=0.0004) and higher thermal detection threshold to warm stimuli (p=0.023 and p=0.004 for hand and foot, respectively). There was no evidence for associations between other neurological biomarkers and DSPN or nerve function measures.Conclusions/interpretationOur findings in individuals recently diagnosed with diabetes provide new evidence associating higher serum NFL levels with DSPN and peripheral nerve dysfunction. The present study advocates NFL as a potential biomarker for DSPN.

Project description:BACKGROUND:As surgical mortality decreases and endovascular utilization increases, it is unknown whether volume-outcome relationships exist in thoracic aortic dissection repair. We characterized volume-outcome relationships for surgical and endovascular management of thoracic aortic dissection. METHODS:Patients aged more than 18 years undergoing repair of thoracic aortic dissection in the United States between 2010 and 2014 were identified in seven all-payer state inpatient administrative databases. Patients were divided into groups based on type of repair: surgical repair of type A dissection (TAAD), surgical repair of type B dissection (TBAD), and endovascular repair (TEVAR). Hierarchical logistic regression models evaluated the association between hospital volume and in-hospital mortality. RESULTS:Overall in-hospital mortality rate was 13.4% (890 of 6650), highest after TAAD (463 of 2918, 15.9%), followed by TBAD (270 of 1934, 14.0%) and TEVAR (157 of 1798, 8.7%). Volume-outcome relationships for adjusted in-hospital mortality were demonstrated for TAAD and TBAD (P-trend < .001), but not TEVAR (P-trend = .11). Adjusted in-hospital mortality differed most for TAAD (fewer than 3 cases per year: 21%, 95% confidence interval, 18% to 24%; vs 11 or more cases per year: 12%, 95% confidence interval, 8% to 16%; P < .001) and TBAD (fewer than 2 cases per year: 18%, 95% confidence interval, 15% to 22%; vs 11 or more cases per year: 9%, 95% confidence interval, 5% to 12%; P < .001), whereas TEVAR did not differ between quartiles. Adjusted mortality was lower at centers with 26 or more overall annual thoracic dissection repairs, compared with any of the three lower-volume quartiles (P < .001). CONCLUSIONS:This study demonstrated lower mortality at high-volume hospitals for overall repair of aortic dissection, persisting separately for surgical repair of TAAD and TBAD, but not TEVAR. As endovascular technology advances and practice patterns consequently change, analyses should focus on understanding the balance between procedural volume, mortality, and access to care for thoracic aortic dissection.

Project description:BACKGROUND:Spinocerebellar ataxia type 3 (SCA3) is the most common subtype of autosomal dominantly inherited spinocerebellar ataxias (SCAs). No validated blood biomarker is available to assess either disease progression or therapeutic response. Neurofilament light chain (NfL) was recently proposed as a serum biomarker for many neurodegenerative disorders. The present study investigated whether NfL was a promising serum biomarker for SCA3. METHODS:Seventeen SCA3 patients and 9 controls were enrolled in cohort A, and 116 SCA3 individuals (preclinical and patients) and 91 controls were recruited as cohort B. We assessed whether serum NfL correlated with cerebrospinal fluid (CSF) NfL in cohort A and correlations between serum NfL levels and clinical features and brain volumes were determined in cohort B. The single-molecule array method was used to measure serum NfL levels. Disease severity was determined using the scale for the assessment and rating of ataxia (SARA) and the international cooperative ataxia rating scale (ICARS). Cerebellar and brainstem volumes were assessed using MRI neuroimaging measurements. RESULTS:Serum/CSF NfL levels in cohort A were elevated in SCA3 patients, and serum and CSF NfL exhibited a significant positive correlation (r = 0.9179, p < 0.0001). Levels of serum NfL in cohort B were significantly higher in preclinical SCA3 (15.03 ± 7.49 vs 6.88 ± 2.72 pg/ mL, p < 0.0001) and manifest SCA3 subjects (37.56 ± 13.47 vs 9.07 ± 6.02 pg/ mL, p < 0.0001) compared to those in controls. Serum NfL concentrations increased from early disease stage to the next stage. Levels of serum NfL in ATXN3 mutation carriers were positively associated with SARA (r = 0.5458, p < 0.0001) and ICARS scores (r = 0.5522, p < 0.0001). Significant negative associations with cerebellar volumes (r = - 0.4217, p = 0.0003) and brainstem volumes (r = - 0.4263, p = 0.0003) were observed. All changes remained significant after adjustment for age and CAG repeat. CONCLUSIONS:Levels of serum NfL were significantly elevated in SCA3 individuals and correlated with disease severity. Serum NfL is a promising serum biomarker of disease onset and progression, and a potential candidate biomarker of treatment response in SCA3.

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Neurofilament Light Chain Protein Is a Predictive Biomarker for Stroke After Surgical Repair for Acute Type A Aortic Dissection.

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