Dynamic changes of peripheral inflammatory markers link with disease severity and predict short-term poor outcome of myasthenia gravis.

The relationship between peripheral inflammatory markers, their dynamic changes, and the disease severity of myasthenia gravis (MG) is still not fully understood. Besides, the possibility of using it to predict the short-term poor outcome of MG patients have not been demonstrated. This study aims to investigate the relationship between peripheral inflammatory markers and their dynamic changes with Myasthenia Gravis Foundation of America (MGFA) classification (primary outcome) and predict the short-term poor outcome (secondary outcome) in MG patients. The study retrospectively enrolled 154 MG patients from June 2016 to December 2021. The logistic regression was used to investigate the relationship of inflammatory markers with MGFA classification and determine the factors for model construction presented in a nomogram. Finally, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were utilized to evaluate the incremental capacity. Logistic regression revealed significant associations between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), aggregate index of systemic inflammation (AISI) and MGFA classification (p = 0.013, p = 0.032, p = 0.017, respectively). Incorporating dynamic changes of inflammatory markers into multivariable models improved their discriminatory capacity of disease severity, with significant improvements observed for NLR, systemic immune-inflammation index (SII) and AISI in NRI and IDI. Additionally, AISI was statistically associated with short-term poor outcome and a prediction model incorporating dynamic changes of inflammatory markers was constructed with the area under curve (AUC) of 0.953, presented in a nomograph. The inflammatory markers demonstrate significant associations with disease severity and AISI could be regarded as a possible and easily available predictive biomarker for short-term poor outcome in MG patients.

Choroid plexus-selective inactivation of adenosine A2A receptors protects against T cell infiltration and experimental autoimmune encephalomyelitis.

BACKGROUND: Multiple sclerosis (MS) is one of the most common autoimmune disorders characterized by the infiltration of immune cells into the brain and demyelination. The unwanted immunosuppressive side effect of therapeutically successful natalizumab led us to focus on the choroid plexus (CP), a key site for the first wave of immune cell infiltration in experimental autoimmune encephalomyelitis (EAE), for the control of immune cells trafficking. Adenosine A2A receptor (A2AR) is emerging as a potential pharmacological target to control EAE pathogenesis. However, the cellular basis for the A2AR-mediated protection remains undetermined. METHODS: In the EAE model, we assessed A2AR expression and leukocyte trafficking determinants in the CP by immunohistochemistry and qPCR analyses. We determined the effect of the A2AR antagonist KW6002 treatment at days 8-12 or 8-14 post-immunization on T cell infiltration across the CP and EAE pathology. We determined the critical role of the CP-A2AR on T cell infiltration and EAE pathology by focal knock-down of CP-A2AR via intracerebroventricular injection of CRE-TAT recombinase into the A2ARflox/flox mice. In the cultured CP epithelium, we also evaluated the effect of overexpression of A2ARs or the A2AR agonist CGS21680 treatment on the CP permeability and lymphocytes migration. RESULTS: We found the specific upregulation of A2AR in the CP associated with enhanced CP gateway activity peaked at day 12 post-immunization in EAE mice. Furthermore, the KW6002 treatment at days 8-12 or 8-14 post-immunization reduced T cell trafficking across the CP and attenuated EAE pathology. Importantly, focal CP-A2AR knock-down attenuated the pathogenic infiltration of Th17+ cells across the CP via inhibiting the CCR6-CCL20 axis through NFκB/STAT3 pathway and protected against EAE pathology. Lastly, activation of A2AR in the cultured epithelium by A2AR overexpression or CGS21680 treatment increased the permeability of the CP epithelium and facilitated lymphocytes migration. CONCLUSION: These findings define the CP niche as one of the primary sites of A2AR action, whereby A2AR antagonists confer protection against EAE pathology. Thus, pharmacological targeting of the CP-A2AR represents a novel therapeutic strategy for MS by controlling immune cell trafficking across CP.

Platelet volume indices for the prognosis of acute ischemic stroke patients with intravenous thrombolysis.

OBJECTIVE: We aimed to investigate whether platelet volume indices (PVIs) were associated with an unfavorable clinical outcome in acute ischemic stroke (AIS) patients undergoing intravenous thrombolysis (IVT). METHODS: We defined a modified Rankin Scale (mRS) score of 3-6 at 90 days as an unfavorable outcome. Logistic regression analysis was performed to find out whether mean platelet volume (MPV), platelet distribution width (PDW), MPV/platelet count (PC) ratio and PDW/PC ratio were associated with poor prognosis. A Spearman correlation test was carried out to assess the relationship between variables. RESULTS: Overall, 183 patients were included in this study. Multivariate logistic regression analysis revealed that MPV (adjusted odds ratio [OR] 1.52, 95% confidence interval [CI]: 1.01-2.29, p = 0.044) and PDW-sd (adjusted OR 1.30, 95% CI: 1.06-1.59, p = 0.011) were independent predictors of the poor outcome. There was a trend of incremental OR when compared higher tertile of MPV with lower ones (second tertile, adjusted OR 2.52,95% CI：1.02-6.21, p = 0.045； third tertile, adjusted OR 2.61, 95% CI: 1.12-6.09, p = 0.027). Besides, we found a significant positive correlation between MPV and PDW-sd (or =0.874, p < 0.001). CONCLUSION: MPV and PDW-sd were independent predictors for 90-day outcomes in stroke patients receiving thrombolysis.

Myasthenia gravis and chronic inflammatory demyelinating polyneuropathy in the same patient - a case report.

PURPOSE: To investigate the clinical character, diagnosis and treatment of chronic inflammatory demyelinating polyneuropathy accompanying myasthenia gravis so as to improve the understanding of such diseases. MATERIALS AND METHODS: A case of chronic inflammatory demyelinating polyneuropathy combined with myasthenia gravis were analyzed retrospectively with review of the literature. RESULTS: This man was presented with chronic progressive sensory symptoms, flaccid tetraparesis, areflexia and protein-cell dissociation of cerebrospinal fluid. Nerve conduction study was indicative of demyelinating neuropathy. He was suspected as chronic inflammatory demyelinating polyneuropathy and treated with high-dose glucocorticoids. However, his condition worsened. Four months later, he was admitted and was diagnosed as combination of chronic inflammatory demyelinating polyneuropathy and myasthenia gravis. Good clinical results were observed after he was treated with pyridostigmine bromide, prednisone and mycophenolate mofetil. CONCLUSIONS: This case warns clinicians to be aware of these two diseases presenting in the same patient, and the possible implications on treatment choices. A common immunological abnormality might exist in this rare association, but it still remains unknown.

The clinical significance of neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio in Guillain-Barré syndrome.

Purpose/Aim of the study: Guillain Barré syndrome (GBS) is a severe peripheral nervous disease that leads to muscle weakness and areflexia. We now commonly accept a synthesis that inflammation and immunity play key role in GBS pathogenesis. Many studies pointed out that neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) are novel promising markers of inflammation or immunity. Our study aimed to evaluate whether the NLR and the MLR were associated to GBS or not. MATERIALS AND METHODS: We measured blood cell count in 334 individuals including 117 GBS and 217 healthy controls. RESULTS: Our findings demonstrated that the GBS patients had higher levels of NLR and MLR than the healthy controls. The severe group also had higher levels of NLR and MLR compared to the mild group. We took the method of receiver-operating characteristic curve to find out the cut-off value of NLR for GBS occurrence and severity; it was 2.295 and 3.05, respectively. The cut-off values of MLR for GBS incidence and severity were the same, it was 0.235. CONCLUSION: In the setting of GBS, the NLR and MLR were significantly increased and they may be pathophysiologically and clinically relevant in GBS. The NLR and MLR would be new biomarkers of medical application.

Mean platelet volume/platelet count ratio as a predictor of 90-day outcome in large artery atherosclerosis stroke patients.

OBJECTIVE: Previous studies reported a lower platelet count (PC) level and a higher mean platelet volume (MPV) level in severe ischemic stroke. We define MPV/PC as the platelet ratio (PR). This study investigates the relationship between PR and 90-day outcome of large artery atherosclerosis (LAA) stroke. MATERIALS AND METHODS: A retrospective analysis was conducted on 338 LAA patients in two hospitals by looking up the electronic medical record (EMR). The 90-day functional outcome was divided into good and poor according to the modified Rankin Scale (mRS) score. RESULTS: Multivariate logistic regression analysis of the First Affiliated Hospital of Wenzhou Medical University (Hospital 1) revealed that PR (OR1.083, 95%CI [1.044, 1.123], P < 0.001) and National Institutes of Health Stroke Scale (NIHSS) score were independent predictors of the poor outcome. Analysis from the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (Hospital 2) showed that PR (OR1.071, 95%CI [1.039, 1.104], P < 0.001), NIHSS score and age were independent adverse prognostic predictors. Furthermore, higher quartiles of PR presented an incremental OR value compared to the first quartile PR in multivariate regression. In Hospital 1, the cut-off value of PR to predict 90-day outcome was 39.23 (sensitivity: 74.24%, specificity: 55.17%, area under the curve (AUC): 0.694, P < 0.001). In Hospital 2, the optimal cut-off value of PR was 46.08 (sensitivity: 61.40%, specificity: 73.74%, AUC: 0.695, P < 0.001). CONCLUSIONS: Platelet ratio on admission is an independent predictor for 90-day outcome in LAA stroke patients and it has a good predictive effect.

Thyroid hormone level is associated with the frequency and severity of Guillain-Barré syndrome.

OBJECTIVE: Guillain-Barré syndrome (GBS) is a neurodegenerative and inflammatory demyelination disorder, and oxidative stress is concerned with the pathogenesis of the disease. Also, we found that thyroid hormone level is correlated to the oxidative and antioxidant status in previous studies. Our study was aimed to find the possible relationship between the frequency and severity of GBS and thyroid hormone levels. MATERIALS AND METHODS: We measured serum levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) in 238 individuals, including 90 GBS, 44 multiple sclerosis and 104 healthy controls. RESULTS: Our findings demonstrate that the patients with GBS had lower TSH and higher FT4, FT4/FT3 than healthy controls in the normal range. Furthermore, it was also shown in our study that TSH levels in patients with GBS were correlated with disease severity measured by the Hughes Functional Grading Scale. CONCLUSION: Lower TSH, higher FT4 and FT4/FT3 stand for the oxidative status and are associated with the incidence and severity of GBS.

Antioxidant status of serum bilirubin and uric acid in patients with polymyositis and dermatomyositis.

OBJECTIVE: Oxidative stress and variations in antioxidant status are implicated in the pathogenesis of inflammatory and autoimmune diseases. Polymyositis and dermatomyositis (PM/DM) are autoimmune diseases with inflammatory cells infiltrating into skeletal muscles, and the antioxidant status is still controversial. The aim of our study was to investigate the correlation between PM/DM and the antioxidant status of serum bilirubin (Tbil, Dbil and Ibil) and uric acid (UA). MATERIALS AND METHODS: We measured serum concentrations of bilirubin (Tbil, Dbil and Ibil) and uric acid in 384 individuals, including 110 PM/DM patients and 274 healthy controls. RESULTS: We found that PM/DM patients had significantly lower serum concentrations of bilirubin (Tbil and Ibil) and uric acid than healthy controls, whether male or female. Also, after separately adjusting the covariances of age and gender, Tbil, Dbil, Ibil and UA were all relevant factors for PM/DM. Moreover, there were no significant differences in serum antioxidant molecule levels between PM and DM subgroups. CONCLUSION: Our study demonstrated the low serum levels of bilirubin and uric acid in patients with PM/DM. This suggested low antioxidant status in PM/DM patients with excessive oxidative stress.

Platelet-to-White Blood Cell Ratio: A Prognostic Predictor for 90-Day Outcomes in Ischemic Stroke Patients with Intravenous Thrombolysis.

BACKGROUND: This study is aimed to investigate the relationship between platelet-to-white blood cell ratio (PWR) and 90-day outcomes in acute stroke patients with intravenous thrombolysis (IVT). MATERIALS AND METHODS: A retrospective analysis was performed on 168 patients receiving IVT for acute ischemic stroke. Complete blood count evaluation was conducted at admission before IVT. A modified Rankin Scale (mRS) score of 3-6 at 90 days was considered an unfavorable outcome. RESULTS: A total of 168 patients were included from 2013 to 2015. The mean age of the sample was 64.6 (±12.3) years, and 23.2% were women. The median baseline National Institutes of Health Stroke Scale score was 7.5 (interquartile range [IQR] 8.0) and the 90-day mRS score was 2 (IQR 2). In our multivariate logistic regression model, a PWR greater than 23.52 (odds ratio .454, 95% confidence interval: .212-.973, P < .050) was a predictor of 90-day outcomes. In addition, there was a significant difference in the PWR values of patients between favorable outcome and unfavorable outcome in the large-artery atherosclerosis subtype (28.241 ± 11.581 and 21.899 ± 9.107, respectively; P = .005). CONCLUSIONS: The PWR at admission predicts 90-day outcomes in ischemic stroke patients with IVT. With the easy and routine use of hemogram analysis, the PWR should be investigated in further prospective randomized controlled trials of acute stroke.

The relationship between neuromyelitis optica spectrum disorder and autoimmune diseases.

Objective: There have been reports of neuromyelitis optica spectrum disorder (NMOSD) coexisting with connective tissue disorders. The objective of this study was to describe the characteristics of NMOSD coexisting with autoimmune diseases (AID). Methods: This retrospective study evaluated NMOSD patients with and without AID. The enrolled patients had at least one attack, with duration of more than 1 year. Data on the demographics, clinical features, and laboratory findings were assessed. The Poisson model was used to investigate the risk factors associated with the annualized relapse rate (ARR), whereas the Cox model was used to evaluate the risk factors for the first relapse. Results: A total of 180 patients (154 women and 26 men) with NMOSD were identified: 45 had AID and 135 did not. Female patients had a higher prevalence of concomitant AID (p = 0.006) and a greater relapse rate within the first year. There were no statistically significant differences in the characteristics of patients. Kaplan-Meier analysis revealed that NMOSD patients with seropositive aquaporin 4 antibodies (AQP4-Ab; log-rank: p = 0.044), had a shorter time to relapse. Patients seropositive for AQP4-Ab (HR = 2.402, 95%CI = 1.092-5.283, p = 0.029) had a higher risk of suffering a first relapse, according to the Cox model. Patients with and without AID showed a similar declining tendency in terms of change in ARR throughout the first 5 years of the disease. The ARR was greater in the first year [incidence rate ratio (IRR) = 1.534, 95%CI = 1.111-2.118] and the first 2 years (IRR = 1.474, 95%CI = 1.056-2.058) in patients with coexisting AID diagnosis prior to the NMOSD onset. Conclusions: Patients with NMOSD with coexisting AID had similar characteristics when compared with those without AID. NMOSD patients with AID diagnosed before onset had a higher risk of relapse in the early stage of the disease.

Systemic Inflammatory Response Index, a Potential Inflammatory Biomarker in Disease Severity of Myasthenia Gravis: A Pilot Retrospective Study.

Purpose: Myasthenia gravis (MG) is a chronic autoimmune disease caused by neuromuscular junction (NMJ) dysfunction. Our current understanding of MG's inflammatory component remains poor. The systemic inflammatory response index (SIRI) presents a promising yet unexplored biomarker for assessing MG severity. This study aimed to investigate the potential relationship between SIRI and MG disease severity. Patients and Methods: We conducted a retrospective analysis of clinical data from 171 MG patients admitted between January 2016 and June 2021. Patients with incomplete data, other autoimmune diseases, or comorbidities were excluded. Disease severity was evaluated using the Myasthenia Gravis Foundation of America (MGFA) classification and Myasthenia Gravis Activities of Daily Living (MG-ADL) on admission. The association between SIRI and disease severity was assessed through logistic regression analysis, along with receiver operating characteristic (ROC) curve and decision curve analysis (DCA) comparisons with established inflammation indicators. Results: After exclusion, 143 patients were analyzed in our study. SIRI levels significantly differed between patients with higher and lower disease severity (p < 0.001). Univariate logistic regression showed that SIRI had a significant effect on high disease severity (OR = 1.376, 95% CI 1.138-1.664, p = 0.001). This association remained significant even after adjusting for age, sex, disease duration, history of MG medication and thymoma (OR = 1.308, 95% CI 1.072-1.597, p = 0.008). Additionally, a positive correlation between SIRI and MG-ADL was observed (r = 0.232, p = 0.008). Significant interactions were observed between SIRI and immunosuppressor (p interaction = 0.001) and intravenous immunoglobulin (p interaction = 0.005). DCA demonstrated the superior net clinical benefit of SIRI compared to other markers when the threshold probability was around 0.2. Conclusion: Our findings indicate a strong independent association between SIRI and disease severity in MG, suggesting SIRI's potential as a valuable biomarker for MG with superior clinical benefit to currently utilized markers.

Association of nutritional screening tools with 6-month outcomes in ischemic stroke patients: A retrospective study.

OBJECTIVE: Nutritional screening tools based on laboratory examinations are relatively objective and available indicators. However, few studies have investigated whether malnutrition severity might be associated with adverse outcomes at the platform recovery period of 6 mo and differentiated in acute ischemic stroke patients with or without intravenous thrombolysis. Therefore, we assessed the association between malnutrition and 6-mo outcomes in both intravenous thrombolysis and non-intravenous thrombolysis patients. METHODS: We retrospectively recruited 138 acute ischemic stroke patients who received intravenous thrombolysis and 311 who did not. The Geriatric Nutritional Risk Index, prognostic nutritional index, and Controlling Nutritional Status were used to assess nutritional status. The concordance between the 3 malnutrition screening tools was investigated with the κ statistic. Subgroups analyses were conducted to assess the correlation between malnutrition and functional outcomes in intravenous thrombolysis and non-intravenous thrombolysis patients. RESULTS: A total of 17 (6.44%) patients were suffering from malnutrition, as indicated by the Geriatric Nutritional Risk Index, prognostic nutritional index, and Controlling Nutritional Status jointly. Moderate-severe malnutrition evaluated by the Geriatric Nutritional Risk Index was significantly associated with poor functional outcome (odds ratio = 4.074; P = 0.003). Patients in the good functional outcome group (modified Rankin scale scores = 0 to 2) had a higher proportion of intravenous thrombolysis treatment (32.79% versus 21.25%; P = 0.043). Furthermore, subgroup analyses found no significant interactions between malnourished levels and intravenous thrombolysis treatment (P interaction > 0.05). CONCLUSION: The Geriatric Nutritional Risk Index, over ≤24 h, compared with the prognostic nutritional index and Controlling Nutritional Status, provided timely signals to improve acute ischemic stroke patients' nutritional status. Also, nutritional status might not lead todifferent 6-mo outcomes, whether or not patients received intravenous thrombolysis treatment.

Prediction of trends in unfavorable prognosis in patients with acute ischemic stroke according to low left ventricular ejection fraction levels.

As few studies have reported the impact of lower left ventricular ejection fraction (LVEF) on the prognosis of acute ischemic stroke (AIS) patients, we aimed to explore this through a retrospective cohort study and a meta-analysis. A total of 283 AIS patients receiving intravenous thrombolysis at the Third Affiliated Hospital of Wenzhou Medical University between 2016 and 2019 were enrolled and divided into three groups based on LVEF tertiles. The logistic regression model estimated the association between LVEF and the three-month AIS prognosis. After adjusting for confounding factors, patients in tertile 3 exhibited an increased risk of poor functional outcome and mortality [odds ratio (OR), 2.656 (95% CI: 1.443-4.889); OR, 7.586 (95% CI: 2.102-27.375)]. A systematic search of PubMed, EMBASE and Cochrane Library was performed. Our meta-analysis revealed that LVEF < 40% was significantly associated with poor functional outcome [OR 1.94 (95% CI: 1.08-3.50)], mortality [OR 3.69 (95% CI: 1.22-11.11)], as well as LVEF < 55% [OR 1.68 (95% CI: 1.22-2.32); 2.27 (95% CI: 1.30-3.96)], respectively. A decreased LVEF could predict an inferior prognosis for AIS; therefore, it could aid in clinical decision-making in this patient population.

Targeted Knockdown of Genes in the Choroid Plexus.

The choroid plexus (ChP) serves as a critical gateway for immune cell infiltration into the central nervous system (CNS) under both physiological and pathological conditions. Recent research has shown that regulating ChP activity may offer protection against CNS disorders. However, studying the biological function of the ChP without affecting other brain regions is challenging due to its delicate structure. This study presents a novel method for gene knockdown in ChP tissue using adeno-associated viruses (AAVs) or cyclization recombination enzyme (Cre) recombinase protein consisting of TAT sequence (CRE-TAT). The results demonstrate that after injecting AAV or CRE-TAT into the lateral ventricle, the fluorescence was exclusively concentrated in the ChP. Using this approach, the study successfully knocked down the adenosine A2A receptor (A2AR) in the ChP using RNA interference (RNAi) or Cre/locus of X-overP1 (Cre/LoxP) systems, and showed that this knockdown could alleviate the pathology of experimental autoimmune encephalomyelitis (EAE). This technique may have important implications for future research on the ChP's role in CNS disorders.

Elevated Albumin to Globulin Ratio on Day 7 is Associated with Improved Function Outcomes in Acute Ischemic Stroke Patients with Intravenous Thrombolysis.

Background and Purpose: Albumin to globulin ratio (A/G) has been established as a representative biomarker for assessing inflammation and nutritional status. However, the prognostic value of A/G has rarely been reported in acute ischemic stroke (AIS) patients with intravenous thrombolysis (IVT). Methods: A total of 311 AIS patients who had undergone IVT and completed 3-month follow-up were retrospectively recruited in this study. Albumin (Alb), globulin (Glb) and A/G on admission, within 24 hours after IVT and on day 7 were recorded. Poor outcome was defined as death or major disability (modified Rankin Scale, 3-6) at 3 months. Results: Among the 311 cases, 260 patients had admission blood samples, 296 cases had blood samples within 24 hours after IVT and 126 cases had blood samples on day 7. The patients with and without available blood samples were well-balanced. During the first 24 h, we observed A/G to increase significantly compared with baseline whereas at day 7 it was almost back to baseline in patients with a poor outcome. Receiver operating characteristic (ROC) curves analysis showed that A/G had a better performance in discriminating patients at high risk and low risk of a poor outcome than either Alb or Glb alone and carried the highest predictive ability on day 7 (AUC = 0.807). Lower 7-day A/G was independently associated with a poor outcome (per-SD increase, OR = 0.182, 95% CI: 0.074-0.446). Conclusion: A/G is an important prognostic indicator for AIS outcomes and merits dynamic monitoring.

Predictive Value of Globulin to Prealbumin Ratio for 3-Month Functional Outcomes in Acute Ischemic Stroke Patients.

Objective: We aimed to evaluate and compare the association between globulin to albumin ratio (GAR) and globulin to prealbumin ratio (GPR) and 3-month functional prognosis of acute ischemic stroke (AIS) patients receiving intravenous thrombolysis therapy. Methods: 234 AIS patients undergoing intravenous thrombolysis were retrospectively enrolled with acute ischemic stroke from February 2016 to October 2019. Blood sample was collected within 24 h after admission. Poor outcome was defined as the modified Rankin Scale (mRS) ≥ 3 and a favorable outcome as mRS < 3. Severe stroke was defined as the National Institutes of Health Stroke Scale (NIHSS) score > 10 on admission. Student's t-test, Mann-Whitney U test, Chi-square test, logistics' regression analysis, and receiver operating characteristic (ROC) analysis were performed. Results: Patients with poor functional outcome had higher GAR and GPR levels compared with favorable functional group (p = 0.001, p < 0.001, respectively). Severe stroke was also associated with these two increasing variables. After adjustment for confounding factors, multivariate logistic regression analysis indicated that GPR was an independent indicator predictor of AIS. Conclusions: The 24 h GPR level can predict the 3-month functional outcome in AIS patients accepting recombinant tissue plasminogen activator (r-tPA) intravenous thrombosis.

Admission Random Blood Glucose, Fasting Blood Glucose, Stress Hyperglycemia Ratio, and Functional Outcomes in Patients With Acute Ischemic Stroke Treated With Intravenous Thrombolysis.

BACKGROUND: Stress hyperglycemia ratio (SHR), calculated as glucose/glycated hemoglobin, has recently been developed for assessing stress hyperglycemia and could provide prognostic information for various diseases. However, calculating SHR using random blood glucose (RBG) drawn on admission or fasting blood glucose (FBG) could lead to different results. This study intends to evaluate the association between SHR and functional outcomes in patients with acute ischemic stroke (AIS) with recombinant tissue plasminogen activator (r-tPA) intravenous thrombolysis. METHODS: Data from 230 patients with AIS following thrombolytic therapy with r-tPA in the Third Affiliated Hospital of Wenzhou Medical University from April 2016 to April 2019 were retrospectively reviewed. SHR1 was defined as [RBG (mmol/L)]/[HbA1c (%)] and SHR2 was defined as [FBG (mmol/L)]/[HbA1c (%)]. The outcomes included early neurological improvement (ENI), poor function defined as a modified Rankin Scale score (mRS) of 3-6, and all-cause death in 3 months. Multivariable logistic regression was performed to estimate the association between SHR and adverse outcomes. RESULTS: After adjustment for possible confounders, though patients with AIS with higher SHR1 tend to have a higher risk of poor outcome and death and unlikely to develop ENI, these did not reach the statistical significance. In contrast, SHR2 was independently associated with poor functional outcome (per 0.1-point increases: odds ratios (OR) = 1.383 95% CI [1.147-1.668]). Further adjusted for body mass index (BMI), triglyceride-glucose index (TyG), and diabetes slightly strengthen the association between SHR (both 1 and 2) and adverse outcomes. In subgroup analysis, elevated SHR1 is associated with poor functional outcomes (per 0.1-point increases: OR = 1.246 95% CI [1.041-1.492]) in non-diabetic individuals and the association between SHR2 and the poor outcomes was attenuated in non-cardioembolic AIS. CONCLUSION: SHR is expected to replace random or fasting glucose concentration as a novel generation of prognostic indicator and a potential therapeutic target.

The white blood cell count to mean platelet volume ratio for ischemic stroke patients after intravenous thrombolysis.

Background and Purpose: White blood cell count to mean platelet volume ratio (WMR) is increasingly recognized as a promising biomarker. However, its predictive capability for acute ischemic stroke (AIS) patients is relatively less researched. The primary aim of this study is to explore its prognostic value in AIS patients after reperfusion regarding 3-month poor functional outcome. Methods: A total of 549 AIS patients who had undergone vascular reperfusion procedure with complete 3-month follow-up were retrospectively recruited in this study. White blood cell count, mean platelet volume at 24 h of admission were recorded. Stroke severity had been estimated using the National Institutes of Health Stroke Scale (NIHSS) and poor outcome was defined as modified Rankin Scale (mRS) 3-6 at 3 months. Results: AIS patients with poor functional outcome at 3 months displayed higher WMR. A positive correlation between WMR and NIHSS score was found (r = 0.334, p < 0.001). After adjusting potential confounders, WMR was still an independent risk factor for poor prognosis at 3 months (OR = 2.257, 95% CI [1.117-4.564], p = 0.023) in multivariate logistic regression model. Subgroup analyses further suggested a significant association between WMR and poor outcome in high baseline NIHSS (per 0.1-point increase: OR = 1.153, 95% CI [1.014-1.312], p = 0.030) group. Receiver operating characteristic (ROC) curves analysis was utilized to assess the predictive ability of WMR, indicating a cut-off value of 0.86. A nomogram that includes age, sex, NIHSS on admission, high WMR for predicting 1-year all-cause survival was also developed (C-index = 0.628). Conclusions: WMR is significantly correlated with stroke severity on admission and is proved to be an important prognostic indicator for AIS outcomes, especially in high NIHSS on admission group. Additionally, the developed nomogram that includes high WMR for predicting 1-year survival provides us with an effective visualization tool.

A comparative analysis of 375 patients with lateral and medial medullary infarction.

BACKGROUND: Few studies have compared the etiology and clinical features between pure lateral medullary infarction (LMI) and pure medial medullary infarction (MMI). METHODS: All patients included were hospitalized at The First Affiliated Hospital and The Second Affiliated Hospital of Wenzhou Medical University from January 2015 to July 2020. Their risk factors, clinical manifestation, stroke mechanisms and short-term prognosis were analyzed retrospectively. RESULTS: Among the 387 patients enrolled, 266 (68.7%) had LMI, 109 (28.2%) had MMI, and 12 (3.1%) (nine men and three women) had LMI plus MMI. We analyzed the 375 patients of LMI and MMI. The average ages of LMI and MMI were 59.4 years and 62.69 years, respectively. Univariate analysis and multivariable logistic regression was used to investigate the existing risk factors of MMI relative to LMI. Prior infarction, poor glycemic control, and atherosclerosis were more frequently associated with MMI than with LMI. The clinical manifestation was significantly different between LMI and MMI. We used modified Rankin Scale (mRS) score as the short-term prognostic evaluation criteria, and MMI appeared worse than LMI. CONCLUSIONS: This study reveals that: (1) patients with MMI are older than those with LMI; (2) prior infarction, poor glycemic control, and atherosclerosis are independent risk factors of MMI than that of LMI; (3) the clinical manifestations of LMI and MMI are heterogeneous; (4) short-term prognosis of MMI is worse than LMI.

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.