Identifying Risk Factors for Prolonged Length of Stay in Hospital and Developing Prediction Models for Patients with Cardiac Arrest Receiving Targeted Temperature Management.

Background: Prolonged length of stay (LOS) following targeted temperature management (TTM) administered after cardiac arrest may affect healthcare plans and expenditures. This study identified risk factors for prolonged LOS in patients with cardiac arrest receiving TTM and explored the association between LOS and neurological outcomes after TTM. Methods: The retrospective cohort consisted of 571 non-traumatic cardiac arrest patients aged 18 years or older, treated with cardiopulmonary resuscitation (CPR), had a Glasgow Coma Scale score < 8, or were unable to comply with commands after the restoration of spontaneous circulation (ROSC), and received TTM less than 12 hours after ROSC. Prolonged LOS was defined as LOS beyond the 75th quartile of the entire cohort. We analyzed and compared relevant variables and neurological outcomes between the patients with and without prolonged LOS and established prediction models for estimating the risk of prolonged LOS. Results: The patients with in-hospital cardiac arrest had a longer LOS than those with out-of-hospital cardiac arrest (p = 0.0001). Duration of CPR (p = 0.02), underlying heart failure (p = 0.001), chronic obstructive pulmonary disease (p = 0.008), chronic kidney disease (p = 0.026), and post-TTM seizures (p = 0.003) were risk factors for prolonged LOS. LOS was associated with survival to hospital discharge, and patients with the lowest and highest Cerebral Performance Category scores at discharge had a shorter LOS. A logistic regression model based on parameters at discharge achieved an area under the curve of 0.840 to 0.896 for prolonged LOS prediction, indicating the favorable performance of this model in predicting LOS in patients receiving TTM. Conclusions: Our study identified clinically relevant risk factors for prolonged LOS following TTM and developed a prediction model that exhibited adequate predictive performance. The findings of this study broaden our understanding regarding factors associated with hospital stay and can be beneficial while making clinical decisions for patients with cardiac arrest who receive TTM.

Therapeutic hypothermia in patients after cardiac arrest: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Targeted temperature management (TTM) with therapeutic hypothermia (TH) has been used to improve neurological outcomes in patients after cardiac arrest; however, several trials have reported conflicting results regarding its effectiveness. This systematic review and meta-analysis assessed whether TH was associated with better survival and neurological outcomes after cardiac arrest. METHOD: We searched online databases for relevant studies published before May 2023. Randomized controlled trials (RCTs) comparing TH and normothermia in post-cardiac-arrest patients were selected. Neurological outcomes and all-cause mortality were assessed as the primary and secondary outcomes, respectively. A subgroup analysis according to initial electrocardiography (ECG) rhythm was performed. RESULT: Nine RCTs (4058 patients) were included. The neurological prognosis was significantly better in patients with an initial shockable rhythm after cardiac arrest (RR = 0.87, 95% confidence interval [CI] = 0.76-0.99, P = 0.04), especially in those with earlier TH initiation (<120 min) and prolonged TH duration (≥24 h). However, the mortality rate after TH was not lower than that after normothermia (RR = 0.91, 95% CI = 0.79-1.05). In patients with an initial nonshockable rhythm, TH did not provide significantly more neurological or survival benefits (RR = 0.98, 95% CI = 0.93-1.03 and RR = 1.00, 95% CI = 0.95-1.05, respectively). CONCLUSION: Current evidence with a moderate level of certainty suggests that TH has potential neurological benefits for patients with an initial shockable rhythm after cardiac arrest, especially in those with faster TH initiation and longer TH maintenance.

Application of machine learning-based models to boost the predictive power of the SPAN index.

BACKGROUND: This study re-explored the predictive validity of Stroke Prognostication using Age and National Institutes of Health Stroke Scale (SPAN) index in patients who received different treatments for acute ischemic stroke (AIS) and developed machine learning-boosted outcome prediction models. METHODS: We evaluated the prognostic relevance of SPAN index in patients with AIS who received intravenous tissue-type plasminogen activator (IV-tPA), intra-arterial thrombolysis (IAT) or non-thrombolytic treatments (non-tPA), and applied machine learning algorithms to develop SPAN-based outcome prediction models in a cohort of 2145 hospitalized AIS patients. The performance of the models was assessed and compared using the area under the receiver operating characteristic curves (AUCs). RESULTS: SPAN index ≥100 was associated with higher mortality rate and higher modified Rankin Scale at discharge in AIS patients who received the different treatments. Compared to the lower AUCs for the SPAN-alone model across all groups, the AUCs of the logistic regression-boosted model were 0.838, 0.857, 0.766 and 0.875 for the whole cohort, non-tPA, IV-tPA and IAT groups, respectively. Similarly, the AUCs of the generated artificial neural network were 0.846, 0.858, 0.785 and 0.859 for the whole cohort, non-tPA, IV-tPA and IAT groups, respectively, while for gradient boosting decision tree model, we computed 0.850, 0.863, 0.779 and 0.815. CONCLUSIONS: SPAN index has prognostic relevance in patients with AIS who received different treatments. The generated machine learning-based models exhibit good performance for predicting the functional recovery of AIS; thus, their proposed clinical application to aid outcome prediction and decision-making for the patients with AIS.

Intra-Arterial Thrombectomy for Acute Ischemic Stroke Related to the Procoagulant Effect of Warfarin in A Patient with Atrial Fibrillation and Bioprosthetic Valve Replacement.

PURPOSE: Warfarin is associated with paradoxical procoagulant effect that leads to a transient hypercoagulable state and acute ischemic stroke (AIS). This clinical dilemma is further confounded when the patient has multiple comorbidities and the optimal treatment strategies are unclear. CASE REPORT: We report a 78-year-old male with valvular heart disease, congestive heart failure, and atrial fibrillation, who received bioprosthetic valve replacement and developed AIS related to the paradoxical procoagulant effect of warfarin. Emergent cerebral angiography with mechanical thrombectomy was performed, and recanalization was successfully achieved. After shifting warfarin to nonvitamin K oral anticoagulant (NOAC), the paradoxical procoagulant effect ameliorated. CONCLUSION: This report describes the roles of endovascular therapy and NOAC in patients with similar highly complex conditions and has clinical relevance for therapeutic plans in the clinical setting.

Plasma extracellular vesicles tau and ß-amyloid as biomarkers of cognitive dysfunction of Parkinson's disease.

The contribution of circulatory tau and ß-amyloid in Parkinson's disease (PD), especially the cognitive function, remains inconclusive. Extracellular vesicles (EVs) cargo these proteins throughout the bloodstream after they are directly secreted from many cells, including neurons. The present study aims to investigate the role of the plasma EV-borne tau and ß-amyloid as biomarkers for cognitive dysfunction in PD by investigating subjects with mild to moderate stage of PD (n = 116) and non-PD controls (n = 46). Plasma EVs were isolated, and immunomagnetic reduction-based immunoassay was used to assess the levels of α-synuclein, tau, and ß-amyloid 1-42 (Aß1-42) within the EVs. Artificial neural network (ANN) models were then applied to predict cognitive dysfunction. We observed no significant difference in plasma EV tau and Aß1-42 between PD patients and controls. Plasma EV tau was significantly associated with cognitive function. Moreover, plasma EV tau and Aß1-42 were significantly elevated in PD patients with cognitive impairment when compared to PD patients with optimal cognition. The ANN model used the plasma EV α-synuclein, tau, and Aß1-42, as well as the patient's age and gender, as predicting factors. The model achieved an accuracy of 91.3% in identifying cognitive dysfunction in PD patients, and plasma EV tau and Aß1-42 are the most valuable factors. In conclusion, plasma EV tau and Aß1-42 are significant markers of cognitive function in PD patients. Combining with the plasma EV α-synuclein, age, and sex, plasma EV tau and Aß1-42 can identify cognitive dysfunction in PD patients. This study corroborates the prognostic roles of plasma EV tau and Aß1-42 in PD.

Efficacy and safety of botulinum toxin for treating sialorrhea: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Sialorrhea often happens in patients with neurologic disorders, and botulinum toxin (BoNT), which inhibits acetylcholine activation, may be an effective treatment for drooling. This systematic review and meta-analysis of randomized control trials aims to evaluate the efficacy and safety of BoNT in adults and children with sialorrhea due to neurological disorders. METHODS: The PubMed, Embase, and Cochrane databases were searched for relevant studies published before August 2021. The pooled estimate of outcomes was calculated using a random effect model. RESULTS: The review included 17 studies involving 981 patients. Compared with placebo, both BoNT type A (BoNT-A) and BoNT type B (BoNT-B) alleviated drooling frequency and severity (mean difference, 95% CI; BoNT-A: -1.20, -1.89 to -0.51; BoNT-B: -1.62, -2.07 to -1.17), reduced saliva weight (BoNT-A: -1.70, -2.30 to -1.10; BoNT-B: -1.12, -1.97 to -0.27), and improved global impression of change (BoNT-A: -1.30, -1.73 to -0.86; BoNT-B: -1.58, -1.95 to -1.21) in adults 4 weeks postinjection. BoNT-B remained effective at 12 weeks. In children, BoNT-A and BoNT-B alleviated sialorrhea symptoms (BoNT-A: -1.63, -2.42 to -0.85; BoNT-B: -5.20, -6.03 to -4.37) and BoNT-A reduced saliva weight (-0.77, -1.54 to 0.00) at 4 weeks postinjection. After 12 weeks, BoNT-B remained efficacious. Most adverse effects (AEs) were mild to moderate and self-limited. CONCLUSIONS: There is moderate certainty of evidence (COE) that either BoNT-A or BoNT-B could relieve sialorrhea after 4 and 12 weeks of follow-up without significantly more severe AEs in adults. However, the COE is very low to low in children.

Safety and efficacy of endovascular thrombectomy in acute ischemic stroke treated with anticoagulants: a systematic review and meta-analysis.

BACKGROUND: Endovascular thrombectomy (EVT) is an effective therapy in acute ischemic stroke (AIS) with large vessel occlusion, especially for those who are unsuitable for intravenous thrombolysis. However, the safety and efficacy of EVT in AIS patients who receiving oral anticoagulants (OACs) is unclear, especially for the risk of symptomatic intracranial hemorrhage (sICH).  METHODS: Database of PubMed, Embase, and Cochrane Library were searched from Jan 1, 2000, through the final search date of Jun 2, 2021. Eligible studies for enrollment required outcomes reported for events of sICH, mortality, functional status, and successful reperfusion. Meta-analysis was conducted to compare the outcomes difference after EVT between AIS patients with or without OACs use. The primary safety outcome was sICH after EVT, and the primary efficacy outcome was functional status at 3 months.  RESULTS: One thousand nine hundred forty studies were screened for eligibility and 15 of them were included in the meta-analysis. Compared the OACs group to control arm, vitamin K antagonists (VKAs) was associated with higher risk of sICH (OR 1.49, 95% CI 1.10-2.02) and mortality (OR 1.67, 95% CI 1.35-2.06). Poor functional outcomes were noted both in the VKAs and direct oral anticoagulants (DOACs) groups (OR 0.62, 95% CI 0.54-0.71 and OR 0.61, 95% CI 0.53-0.71, respectively). No differences in successful reperfusion were observed. CONCLUSIONS: Comparing with DOACs, VKAs use was associated with a higher risk of sICH and mortality after EVT. Patients who did not receive OACs exhibited more favorable outcomes. The successful reperfusion did not differ between groups. However, results for mortality and functional outcomes have to be interpreted with caution since they are based on non-randomized data and unadjusted proportions.

Predicting the survivals and favorable neurologic outcomes after targeted temperature management by artificial neural networks.

BACKGROUND: To identify the outcome-associated predictors and develop predictive models for patients receiving targeted temperature management (TTM) by artificial neural network (ANN). METHODS: The derived cohort consisted of 580 patients with cardiac arrest and ROSC treated with TTM between January 2014 and August 2019. We evaluated the predictive value of parameters associated with survival and favorable neurologic outcome. ANN were applied for developing outcome prediction models. The generalizability of the models was assessed through 5-fold cross-validation. The performance of the models was assessed according to the accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). RESULTS: The parameters associated with survival were age, duration of cardiopulmonary resuscitation, history of diabetes mellitus (DM), heart failure, end-stage renal disease (ESRD), systolic blood pressure (BP), diastolic BP, body temperature, motor response after ROSC, emergent coronary angiography or percutaneous coronary intervention (PCI), and the cooling methods. The parameters associated with the favorable neurologic outcomes were age, sex, DM, chronic obstructive pulmonary disease, ESRD, stroke, pre-arrest cerebral-performance category, BP, body temperature, motor response after ROSC, emergent coronary angiography or PCI, and cooling methods. After adequate training, ANN Model 1 to predict survival achieved an AUC of 0.80. Accuracy, sensitivity, and specificity were 75.9%, 71.6%, and 79.3%, respectively. ANN Model 4 to predict the favorable neurologic outcome achieved an AUC of 0.87, with accuracy, sensitivity, and specificity of 86.7%, 77.7%, and 88.0%, respectively. CONCLUSION: The ANN-based models achieved good performance to predict the survival and favorable neurologic outcomes after TTM. The models proposed have clinical value to assist in decision-making.

Efficacy of levetiracetam for migraine prophylaxis: A systematic review and meta-analysis.

BACKGROUND: Migraine is characterized by moderate to severe recurrent headache lasting for 4-72 h. Cortical hyperexcitability may play a crucial role in migraine onset. Therefore, antiepileptic drugs, such as levetiracetam, may be beneficial. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and prospective studies that evaluated the efficacy of levetiracetam in migraine prophylaxis. Electronic databases, including PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, were searched for articles on migraine prophylaxis and levetiracetam published before May 2020. The main outcomes were number of patients with >50% headache frequency reduction, frequency of headache, and headache severity. RESULTS: We identified 4 RCTs involving 192 patients and 4 prospective studies involving 85 patients. The overall data on number of patients with >50% headache frequency reduction, headache frequency, and headache severity were subjected to meta-analysis, which revealed significant differences between the levetiracetam and the placebo groups (risk ratio [RR] of number of patients with >50% headache frequency reduction = 0.46, 95% confidence interval [CI] = 0.35 to 0.61; weighted mean difference [WMD] of headache frequency per month = -3.78, 95% CI = -5.52 to -2.03; standard mean difference [SMD] of headache severity = -2.42, 95% CI = -4.47 to -0.37). CONCLUSION: Our study indicated that levetiracetam can significantly reduce headache frequency and severity in adults and children. Thus, oral levetiracetam can be a therapeutic option for migraine prophylaxis, especially concerning with the adverse effects or teratogenicity of other preventive treatments.

Disseminated cutaneous herpes zoster and multiple cerebral infarcts in an adult with diabetes mellitus.

Ischemic stroke is a rare complication of varicella-zoster virus (VZV) infection. We present the case of a patient with a medical history of type 2 diabetes mellitus (DM) who experienced disseminated cutaneous VZV infection followed by multiple cerebral infarcts associated with VZV vasculopathy. Brain magnetic resonance imaging revealed multiple hyperintense lesions over the bilateral deep white matter and basal ganglia. A skin biopsy revealed small-vessel leukocytoclastic vasculitis with neutrophilic, lymphocytic, and eosinophilic infiltration. This case report describes the rare finding of cutaneous leukocytoclastic vasculitis in VZV infection and highlights that VZV infection is an uncommon but critical etiology of cryptogenic stroke in patients with DM.

Cancer Care Disparities: Overcoming Barriers to Cancer Control in Low- and Middle-Income Countries.

The rising global burden of cancer disproportionately affects low- and middle-income countries (LMICs), which account for over half of new patients and cancer deaths worldwide. However, LMIC health systems face profound challenges in implementing comprehensive cancer control programs because of limited health care resources and infrastructure. This analytical review explores contemporary evidence on barriers undermining cancer control efforts in resource-constrained LMIC settings. We conducted a comprehensive literature review of peer-reviewed evidence on cancer control challenges and solutions tailored to resource-limited settings. We provide a conceptual framework categorizing these barriers across the cancer care continuum, from raising public awareness to palliative care. We also appraise evidence-based strategies proposed to overcome identified obstacles to cancer control in the published literature, including task-shifting to nonspecialist health workers, strategic prioritization of high-impact interventions, regional collaborations, patient navigation systems, and novel financing mechanisms. Developing strong primary care delivery platforms integrated with specialized oncology care, alongside flexible and resilient health system models tailored to local contexts, will be critical to curb the rising tide of cancer in resource-limited settings. Urgent global commitments and investments are needed to dismantle barriers and expand access to prevention, early detection, diagnosis, treatment, and palliation services for all patients with cancer residing in LMICs as an ethical imperative. The review elucidates priority areas for policy actions, health systems strengthening, and future research to guide international efforts toward more equitable cancer control globally.

Plasma extracellular vesicle synaptic proteins as biomarkers of clinical progression in patients with Parkinson's disease.

Synaptic dysfunction plays a key role in Parkinson's disease (PD), and plasma extracellular vesicle (EV) synaptic proteins are emerging as biomarkers for neurodegenerative diseases. Assessment of plasma EV synaptic proteins for their efficacy as biomarkers in PD and their relationship with disease progression was conducted. In total, 144 participants were enrolled, including 101 people with PD (PwP) and 43 healthy controls (HCs). The changes in plasma EV synaptic protein levels between baseline and 1-year follow-up did not differ significantly in both PwP and HCs. In PwP, the changes in plasma EV synaptic protein levels were significantly associated with the changes in Unified Parkinson's Disease Rating Scale (UPDRS)-II and III scores. Moreover, PwP with elevated levels (first quartile) of any one plasma EV synaptic proteins (synaptosome-associated protein 25, growth-associated protein 43 or synaptotagmin-1) had significantly greater disease progression in UPDRS-II score and the postural instability and gait disturbance subscore in UPDRS-III than did the other PwP after adjustment for age, sex, and disease duration. The promising potential of plasma EV synaptic proteins as clinical biomarkers of disease progression in PD was suggested. However, a longer follow-up period is warranted to confirm their role as prognostic biomarkers.

Beyond diagnosis: Leveraging routine blood and urine biomarkers to predict severity and functional outcome in acute ischemic stroke.

Background: The initial severity of acute ischemic stroke (AIS) is a crucial predictor of the disease outcome. In this study, blood and urine biomarkers from patients with AIS were measured to estimate stroke severity and predict long-term stroke outcomes. Methods: The medical records of patients with AIS between October 2016 and May 2020 were retrospectively analyzed. The relationships of blood and urine biomarkers with stroke severity at admission were evaluated in patients with AIS. Predictive models for initial stroke severity and long-term prognosis were then developed using a panel of identified biomarkers. Results: A total of 2229 patients were enrolled. Univariate analysis revealed 12 biomarkers associated with the National Institutes of Health Stroke Scale scores at admission. The area under the curve values for predicting initial stroke severity and long-term prognosis on the basis of these biomarkers were 0.7465, 0.7470, and 0.8061, respectively. Among multiple tested machine-learning, eXtreme gradient boosting exhibited the highest effectiveness in predicting 90-day modified Rankin Scale scores. SHapley Additive exPlanations revealed fasting glucose, albumin, hemoglobin, prothrombin time, and urine-specific gravity to be the top five most crucial biomarkers. Conclusion: These findings demonstrate that clinically available blood and urine biomarkers can effectively estimate initial stroke severity and predict long-term prognosis in patients with AIS. Our results provide a scientific basis for developing tailored clinical treatment and management strategies for AIS, through incorporating liquid biomarkers into stroke risk assessment and patient care protocols for patients with AIS.

The intricate interplay between cancer stem cells and cell-of-origin of cancer: implications for therapeutic strategies.

Background: Cancer stem cells (CSCs) have emerged as pivotal players in tumorigenesis, disease progression, and resistance to therapies. Objective: This comprehensive review delves into the intricate relationship between CSCs and the cell-of-origin in diverse cancer types. Design: Comprehensive review of thematically-relevant literature. Methods: We explore the underlying molecular mechanisms that drive the conversion of normal cells into CSCs and the impact of the cell-of-origin on CSC properties, tumor initiation, and therapeutic responses. Moreover, we discuss potential therapeutic interventions targeting CSCs based on their distinct cell-of-origin characteristics. Results: Accruing evidence suggest that the cell-of-origin, the cell type from which the tumor originates, plays a crucial role in determining the properties of CSCs and their contribution to tumor heterogeneity. Conclusion: By providing critical insights into the complex interplay between CSCs and their cellular origins, this article aims to enhance our understanding of cancer biology and pave the way for more effective and personalized cancer treatments.

Heart failure and angiotensin II modulate atrial Pitx2c promotor methylation.

Heart failure (HF) can increase atrial fibrillation and induce cardiac hypermethylation. The homeobox gene Pitx2c plays important roles in the genesis of atrial fibrillation and the promoter region of Pitx2c contains cytosine-phosphate-guanine islands. Therefore, epigenetic modification by hypermethylation may reduce Pitx2c expression in atrial myocytes. The aim of the present study were to evaluate whether HF can modulate DNA methylation of Pitx2c and the potential mechanisms involved. We used real-time polymerase chain reaction, immunoblotting and pyrosequencing to investigate RNA and protein expression, as well as the methylation of Pitx2c, in isoproterenol-induced HF, healthy rat left atria and in HL-1 cells with and without (control) exposure to angiotensin (Ang) II (0.1 and 1 µmol/L) or isoproterenol (1 or 10 µmol/L) for 24 h. The HF atrium exhibited increased Pitx2c promoter methylation with increased DNA methyltransferase (DNMT) 1 and decreased Pitx2c protein levels compared with the normal atrium. Angiotensin II (0.1 and 1 µmol/L), increased Pitx2c promoter methylation in HL-1 cells with increased DNMT1 and decreased Pitx2c and Kir2.1 protein levels compared with control cells. These effects were attenuated by the methylation inhibitor 5-aza-2'-deoxycytidine (0.1 µmol/L) and by the AngII receptor blocker losartan (10 µmol/L). However, isoproterenol (1 and 10 µmol/L) did not change the expression of the Pitx2c, DNMT1 and Kir2.1 proteins. In conclusion, HF induces Pitx2c promoter hypermethylation and AngII may contribute to the hypermethylation in HF.

Systemic lupus erythematosus presented as extensive longitudinal myelitis.

BACKGROUND: longitudinal myelitis (LM) is defined by the continuous lesion of more than four spinal cord segments. LM is a rare variant of acute transverse myelitis and it frequently presented poor responses to immunomodulatory therapy, which resulted in severe and disabling sequelae. We reported a case of acute longitudinal myelitis involving extensive lesions from cervical spinal cord to conus medullaris caused by newly diagnosed SLE. CASE REPORT: A 39 years old man who was previously healthy presented to our hospital due to acute urinary retention with progressive lower limb weakness for a week. Brisk deep tendon reflexes in upper limbs and decreased reflexes in lower limbs were noted on admission. The pin-prick, vibration, and light touch sensations were decreased in the lower limbs. Spinal MRI sagittal view showed an T2WI bright up mass in the spinal cord below C3/4 level with extension to conus medullaris. He was diagnosed SLE based on ARA criteria. After ruling out mimics including NMO and MS, SLE with LM explained what happened to him . CONCLUSION: Given the poor prognosis of SLE with LM, which resulted in severe and disabling sequelae. More comprehensive understand of the disease course, real mechanisms and treatment strategy are needed.

Cytokine profiles of plasma extracellular vesicles as progression biomarkers in Parkinson's disease.

BACKGROUND: Inflammation contributes substantially to the pathogenesis of Parkinson's disease (PD). Plasma extracellular vesicle (EV)-derived cytokines are emerging biomarkers of inflammation. We conducted a longitudinal study of the plasma EV-derived cytokine profiles of people with PD (PwP). METHODS: A total of 101 people with mild to moderate PD and 45 healthy controls (HCs) were recruited, and they completed motor assessments (Unified Parkinson Disease Rating Scale [UPDRS]) and cognitive tests at baseline and 1-year follow-up. We isolated the participants' plasma EVs and analyzed their levels of cytokines, including interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-ß. RESULTS: We noted no significant changes in the plasma EV-derived cytokine profiles of the PwPs and HCs between baseline and the 1-year follow-up. Among the PwP, changes in plasma EV-derived IL-1ß, TNF-α and IL-6 levels were significantly associated with changes in the severity of postural instability and gait disturbance (PIGD) and cognition. Baseline plasma EV-derived IL-1ß, TNF-α, IL-6, and IL-10 levels were significantly associated with the severity of PIGD and cognitive symptoms at follow-up, and PwP with elevated IL-1ß and IL-6 levels exhibited significant progression of PIGD over the study period. CONCLUSION: These results suggested the role of inflammation in PD progression. In addition, baseline levels of plasma EV-derived proinflammatory cytokines can be used to predict the progression of PIGD, the most severe motor symptom of PD. Additional studies with longer follow-up periods are necessary, and plasma EV-derived cytokines may serve as effective biomarkers of PD progression.

Plasma extracellular vesicle tau, ß-amyloid, and α-synuclein and the progression of Parkinson's disease: a follow-up study.

Background: Plasma extracellular vesicle (EV) contents are promising biomarkers of Parkinson's disease (PD). The pathognomonic proteins of PD, including α-synuclein, tau, and ß-amyloid, are altered in people with PD (PwP) and are associated with clinical presentation in previous cross-sectional studies. However, the dynamic changes in these plasma EV proteins in PwP and their correlation with clinical progression remain unclear. Objective: We investigated the dynamic changes in plasma EV α-synuclein, tau, and ß-amyloid and their correlation with/prediction of clinical progression in PwP. Design: A cohort study. Methods: In total, 103 PwP and 37 healthy controls (HCs) completed baseline assessment and 1-year follow-up. Clinical assessments included Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III, Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA). Plasma EVs were isolated, and immunomagnetic reduction-based immunoassay was used to assess α-synuclein, tau, and ß-amyloid 1-42 (Aß1-42) levels within the EVs. Results: Compared with HCs, significant differences were noted in the annual changes in all three EV pathognomonic proteins in PwP. Although the absolute changes in plasma EV pathognomonic proteins did not significantly correlate with clinical changes, PwP with elevated baseline plasma EV tau (upper-half) levels demonstrated significantly greater decline in motor and cognition, and increased plasma EV α-synuclein levels were associated with postural instability and the gait disturbance motor subtype. For PwP with elevated levels of all three biomarkers, clinical deterioration was significant, as indicated by UPDRS-II scores, postural instability and gait disturbance subscores of UPDRS-III, and MMSE score. Conclusion: The combination of plasma EV α-synuclein, tau, and Aß1-42 may identify PwP with a high risk of deterioration. Our findings can elucidate the interaction between these pathognomonic proteins, and they may serve as treatment response markers and can be applied in treatment approaches for disease modification.

XGBoost-Based Simple Three-Item Model Accurately Predicts Outcomes of Acute Ischemic Stroke.

An all-inclusive and accurate prediction of outcomes for patients with acute ischemic stroke (AIS) is crucial for clinical decision-making. This study developed extreme gradient boosting (XGBoost)-based models using three simple factors-age, fasting glucose, and National Institutes of Health Stroke Scale (NIHSS) scores-to predict the three-month functional outcomes after AIS. We retrieved the medical records of 1848 patients diagnosed with AIS and managed at a single medical center between 2016 and 2020. We developed and validated the predictions and ranked the importance of each variable. The XGBoost model achieved notable performance, with an area under the curve of 0.8595. As predicted by the model, the patients with initial NIHSS score > 5, aged over 64 years, and fasting blood glucose > 86 mg/dL were associated with unfavorable prognoses. For patients receiving endovascular therapy, fasting glucose was the most important predictor. The NIHSS score at admission was the most significant predictor for those who received other treatments. Our proposed XGBoost model showed a reliable predictive power of AIS outcomes using readily available and simple predictors and also demonstrated the validity of the model for application in patients receiving different AIS treatments, providing clinical evidence for future optimization of AIS treatment strategies.