Pre‐ and post‐conditioning with poly I:C exerts neuroprotective effect against cerebral ischemia injury in animal models: A systematic review and meta‐analysis

BackgroundToll‐like receptor (TLR) agonist polyinosinic–polycytidylic acid (poly I:C) exerts neuroprotective effects against cerebral ischemia (CI), but concrete evidence supporting its exact mechanism of action is unclear.MethodsWe evaluated the neuroprotective role of poly I:C by assessing CI indicators such as brain infarct volume (BIV), neurological deficit score (N.S.), and signaling pathway proteins. Moreover, we performed a narrative review to illustrate the mechanism of action of TLRs and their role in CI. Our search identified 164 articles and 10 met the inclusion criterion.ResultsPoly I:C reduces BIV and N.S. (p = 0.00 and p = 0.03). Interestingly, both pre‐ and post‐conditioning decrease BIV (preC p = 0.04 and postC p = 0.00) and N.S. (preC p = 0.03 and postC p = 0.00). Furthermore, poly I:C upregulates TLR3 [SMD = 0.64; CIs (0.56, 0.72); p = 0.00], downregulates nuclear factor‐κB (NF‐κB) [SMD = −1.78; CIs (−2.67, −0.88); p = 0.0)], and tumor necrosis factor alpha (TNF‐α) [SMD = −16.83; CIs (−22.63, −11.02); p = 0.00].ConclusionWe showed that poly I:C is neuroprotective and acts via the TLR3/NF‐κB/TNF‐α pathway. Our review indicated that suppressing TLR 2/4 may illicit neuroprotection against CI. Further research on simultaneous activation of TLR3 with poly I:C and suppression of TLR 2/4 might open new vistas for the development of therapeutics against CI.     

Loss of long‐term benefit from VIM‐DBS in essential tremor: A secondary analysis of repeated measurements

AimsDeep brain stimulation (DBS) in the ventral intermediate nucleus (Vim‐DBS) is the preferred surgical therapy for essential tremor (ET). Tolerance and disease progression are considered to be the two main reasons underlying the loss of long‐term efficacy of Vim‐DBS. This study aimed to explore whether Vim‐DBS shows long‐term loss of efficacy and to evaluate the reasons for this diminished efficacy from different aspects.MethodsIn a repeated‐measures meta‐analysis of 533 patients from 18 studies, Vim‐DBS efficacy was evaluated at ≤6 months, 7–12 months, 1–3 years, and ≥4 years. The primary outcomes were the score changes in different components of the Fahn‐Tolosa‐Marin Tremor Rating Scale (TRS; total score, motor score, hand‐function score, and activities of daily living [ADL] score). Secondary outcomes were the long‐term predictive factors.ResultsThe TRS total, motor, and ADL scores showed significant deterioration with disease progression (p = 0.002, p = 0.047, and p < 0.001, respectively), while the TRS total (p < 0.001), hand‐function (p = 0.036), and ADL (p = 0.004) scores indicated a significant long‐term reduction in DBS efficacy, although the motor subscore indicated no loss of efficacy. Hand‐function (p < 0.001) and ADL (p = 0.028) scores indicated DBS tolerance, while the TRS total and motor scores did not. Stimulation frequency and preoperative score were predictive factors for long‐term results.ConclusionThis study provides level 3a evidence that long‐term Vim‐DBS is effective in controlling motor symptoms without waning benefits. The efficacy reduction for hand function was caused by DBS tolerance, while that for ADL was caused by DBS tolerance and disease progression. More attention should be given to actual functional recovery rather than changes in motor scores in patients with ET.     

Lithium attenuates blood–brain barrier damage and brain edema following intracerebral hemorrhage via an endothelial Wnt/β‐catenin signaling‐dependent mechanism in mice

BackgroundVasogenic cerebral edema resulting from blood–brain barrier (BBB) damage aggravates the devastating consequences of intracerebral hemorrhage (ICH). Although augmentation of endothelial Wnt/β‐catenin signaling substantially alleviates BBB breakdown in animals, no agents based on this mechanism are clinically available. Lithium is a medication used to treat bipolar mood disorders and can upregulate Wnt/β‐catenin signaling.MethodsWe evaluated the protective effect of lithium on the BBB in a mouse model of collagenase IV‐induced ICH. Furthermore, we assessed the effect and dependency of lithium on Wnt/β‐catenin signaling in mice with endothelial deletion of the Wnt7 coactivator Gpr124.ResultsLithium treatment (3 mmol/kg) significantly decreased the hematoma volume (11.15 ± 3.89 mm³ vs. 19.97 ± 3.20 mm³ in vehicle controls, p = 0.0016) and improved the neurological outcomes of mice following ICH. Importantly, lithium significantly increased the BBB integrity, as evidenced by reductions in the levels of brain edema (p = 0.0312), Evans blue leakage (p = 0.0261), and blood IgG extravasation (p = 0.0009) into brain tissue around the hematoma. Mechanistically, lithium upregulated the activity of endothelial Wnt/β‐catenin signaling in mice and increased the levels of tight junction proteins (occludin, claudin‐5 and ZO‐1). Furthermore, the protective effect of lithium on cerebral damage and BBB integrity was abolished in endothelial Gpr124 knockout mice, suggesting that its protective effect on BBB function was mainly dependent on Gpr124‐mediated endothelial Wnt/β‐catenin signaling.ConclusionOur findings indicate that lithium may serve as a therapeutic candidate for treating BBB breakdown and brain edema following ICH.     

Urinary albumin creatinine ratio associated with postoperative delirium in elderly patients undergoing elective non‐cardiac surgery: A prospective observational study

IntroductionThe blood‐brain barrier (BBB) disruption contributes to postoperative delirium, but cost‐effective and non‐invasive assessment of its permeability is not practicable in the clinical settings. Urine albumin to creatinine ratio (UACR), reflecting systemic vascular endothelial dysfunction, may be a prognostic and predictive factor associated with postoperative delirium. The aim was to analyze the relationship between UACR and postoperative delirium in elderly patients undergoing elective non‐cardiac surgery.Materials and methodsThrough stratified random sampling, a cohort of 408 individuals aged 60 years and older scheduled for elective non‐cardiac surgery were included between February and August 2019 in the single‐center, prospective, observational study. The presence of delirium was assessed using the Confusion Assessment Method (CAM) or Confusion Assessment Method for the ICU (CAM‐ICU) on the day of surgery, at 2 h after the surgery ending time and on the first 3 consecutive days with repeated twice‐daily, with at least 6‐h intervals between assessments. Urine samples were collected on one day before surgery, and 1st day and 3rd day after surgery. The primary outcome was the presence of postoperative delirium, and association of the level of UACR with postoperative delirium was evaluated with unadjusted/adjusted analyses and multivariable logistic regression.ResultsPostoperative delirium was observed in 26.75% (107 of 400) of patients within 3 days post‐surgery. UACR‐Pre (OR, 1.30; 95% CI, 1.14–1.49, p < 0.001), UACR‐POD1 (OR, 1.20; 95% CI, 1.13–1.27, p < 0.001), and UACR‐POD3 (OR, 1.14; 95% CI, 1.08–1.20, p < 0.001) between the delirium and non‐delirium groups show a significant difference, even after adjusting for age, education levels, and other factors.ConclusionAs the marker of endothelial dysfunction, the high perioperative UACR value may be linked to the postoperative delirium in elderly patients undergoing elective non‐cardiac surgery.     

Predictive value of different bilirubin subtypes for clinical outcomes in patients with acute ischemic stroke receiving thrombolysis therapy

AimsTo explore the association of total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL) levels with, as well as the incremental predictive value of different bilirubin subtypes for, poor outcomes in acute ischemic stroke patients after thrombolysis.MethodsWe analyzed 588 individuals out of 718 AIS participants, and all patients were followed up at 3 months after thrombolysis. The primary outcome was 3‐month death and major disability (modified Rankin Scale (mRS) score of 3–6). The secondary outcomes were 3‐month mortality (mRS score of 6), moderate‐severe cerebral edema, and symptomatic intracranial hemorrhage (sICH), respectively.ResultsElevated DBIL pre‐thrombolysis was associated with an increased risk of primary outcome (OR 3.228; 95% CI 1.595–6.535; p for trend = 0.014) after fully adjustment. Elevated TBIL pre‐thrombolysis showed the similar results (OR 2.185; 95% CI 1.111–4.298; p for trend = 0.047), while IBIL pre‐thrombolysis was not significantly associated with primary outcome (OR 1.895; 95% CI 0.974–3.687; p for trend = 0.090). Multivariable‐adjusted spline regression model showed a positive linear dose‐response relationship between DBIL pre‐thrombolysis and risk of primary outcome (p for linearity = 0.004). Adding DBIL pre‐thrombolysis into conventional model had greater incremental predictive value for primary outcome, with net reclassification improvement (NRI) 95% CI = 0.275 (0.084–0.466) and integrated discrimination improvement (IDI) 95% CI = 0.011 (0.001–0.024). Increased DBIL post‐thrombolysis had an association with primary outcome (OR 2.416; 95%CI 1.184–4.930; p for trend = 0.039), and it also elevated the incremental predictive value for primary outcome, with NRI (95% CI) = 0.259 (0.066–0.453) and IDI (95% CI) = 0.025 (0.008–0.043).ConclusionIncreased DBIL pre‐thrombolysis had a stronger association with, as well as greater incremental predictive value for, poor outcomes than TBIL and IBIL did in AIS patients after thrombolysis, which should be understood in the context of retrospective design. The effect of DBIL on targeted populations should be investigated in further researches.     

Identifying a whole‐brain connectome‐based model in drug‐naïve Parkinson's disease for predicting motor impairment

Identifying a whole‐brain connectome‐based predictive model in drug‐naïve patients with Parkinson''s disease and verifying its predictions on drug‐managed patients would be useful in determining the intrinsic functional underpinnings of motor impairment and establishing general brain–behavior associations. In this study, we constructed a predictive model from the resting‐state functional data of 47 drug‐naïve patients by using a connectome‐based approach. This model was subsequently validated in 115 drug‐managed patients. The severity of motor impairment was assessed by calculating Unified Parkinson''s Disease Rating Scale Part III scores. The predictive performance of model was evaluated using the correlation coefficient (r _true) between predicted and observed scores. As a result, a connectome‐based model for predicting individual motor impairment in drug‐naïve patients was identified with significant performance (r _true = .845, p < .001, p _permu = .002). Two patterns of connection were identified according to correlations between connection strength and the severity of motor impairment. The negative motor‐impairment‐related network contained more within‐network connections in the motor, visual‐related, and default mode networks, whereas the positive motor‐impairment‐related network was constructed mostly with between‐network connections coupling the motor‐visual, motor‐limbic, and motor‐basal ganglia networks. Finally, this predictive model constructed around drug‐naïve patients was confirmed with significant predictive efficacy on drug‐managed patients (r = .209, p = .025), suggesting a generalizability in Parkinson''s disease patients under long‐term drug influence. In conclusion, this study identified a whole‐brain connectome‐based model that could predict the severity of motor impairment in Parkinson''s patients and furthers our understanding of the functional underpinnings of the disease.     

Mutation‐related magnetization‐transfer,not axon density,drives white matter differences in premanifest Huntington disease: Evidence from in vivo ultra‐strong gradient MRI

White matter (WM) alterations have been observed in Huntington disease (HD) but their role in the disease‐pathophysiology remains unknown. We assessed WM changes in premanifest HD by exploiting ultra‐strong‐gradient magnetic resonance imaging (MRI). This allowed to separately quantify magnetization transfer ratio (MTR) and hindered and restricted diffusion‐weighted signal fractions, and assess how they drove WM microstructure differences between patients and controls. We used tractometry to investigate region‐specific alterations across callosal segments with well‐characterized early‐ and late‐myelinating axon populations, while brain‐wise differences were explored with tract‐based cluster analysis (TBCA). Behavioral measures were included to explore disease‐associated brain‐function relationships. We detected lower MTR in patients'' callosal rostrum (tractometry: p = .03; TBCA: p = .03), but higher MTR in their splenium (tractometry: p = .02). Importantly, patients'' mutation‐size and MTR were positively correlated (all p‐values < .01), indicating that MTR alterations may directly result from the mutation. Further, MTR was higher in younger, but lower in older patients relative to controls (p = .003), suggesting that MTR increases are detrimental later in the disease. Finally, patients showed higher restricted diffusion signal fraction (FR) from the composite hindered and restricted model of diffusion (CHARMED) in the cortico‐spinal tract (p = .03), which correlated positively with MTR in the posterior callosum (p = .033), potentially reflecting compensatory mechanisms. In summary, this first comprehensive, ultra‐strong gradient MRI study in HD provides novel evidence of mutation‐driven MTR alterations at the premanifest disease stage which may reflect neurodevelopmental changes in iron, myelin, or a combination of these.     

Task‐related neural mechanisms of persecutory ideation in schizophrenia and community monozygotic twin‐pairs

Perceptions of spiteful behavior are common, distinct from rational fear, and may undergird persecutory ideation. To test this hypothesis and investigate neural mechanisms of persecutory ideation, we employed a novel economic social decision‐making task, the Minnesota Trust Game (MTG), during neuroimaging in patients with schizophrenia (n = 30) and community monozygotic (MZ) twins (n = 38; 19 pairs). We examined distinct forms of mistrust, task‐related brain activation and connectivity, and investigated relationships with persecutory ideation. We tested whether co‐twin discordance on these measurements was correlated to reflect a common source of underlying variance. Across samples persecutory ideation was associated with reduced trust only during the suspiciousness condition, which assessed spite sensitivity given partners had no monetary incentive to betray. Task‐based activation contrasts for specific forms of mistrust were limited and unrelated to persecutory ideation. However, task‐based connectivity contrasts revealed a dorsal cingulate anterior insula network sensitive to suspicious mistrust, a left frontal–parietal (lF‐P) network sensitive to rational mistrust, and a ventral medial/orbital prefrontal (vmPFC/OFC) network that was sensitive to the difference between these forms of mistrust (all p < .005). Higher persecutory ideation was predicted only by reduced connectivity between the vmPFC/OFC and lF‐P networks (p = .005), which was only observed when the intentions of the other player were relevant. Moreover, co‐twin differences in persecutory ideation predicted co‐twin differences in both spite sensitivity and in vmPFC/OFC–lF‐P connectivity. This work found that interconnectivity may be particularly important to the complex neurobiology underlying persecutory ideation, and that unique environmental variance causally linked persecutory ideation, decision‐making, and brain connectivity.     

Measuring changes in alcohol use in Finland and Norway during the COVID‐19 pandemic: Comparison between data sources

ObjectivesTo examine (1) how a rapid data collection using a convenience sample fares in estimating change in alcohol consumption when compared to more conventional data sources, and (2) how alcohol consumption changed in Finland and Norway during the first months of the COVID‐19 pandemic.MethodsThree different types of data sources were used for the 2nd quarter of 2020 and 2019: sales statistics combined with data on unrecorded consumption; the rapid European Alcohol Use and COVID‐19 (ESAC) survey (Finland: n = 3800, Norway: n = 17,092); and conventional population surveys (Finland: n = 2345, Norway: n1 = 1328, n2 = 2189, n3 = 25,708). Survey measures of change were retrospective self‐reports.ResultsThe statistics indicate that alcohol consumption decreased in Finland by 9%, while little change was observed in Norway. In all surveys, reporting a decrease in alcohol use was more common than reporting an increase (ratios 2–2.6 in Finland, 1.3–2 in Norway). Compared to conventional surveys, in the ESAC survey fewer respondents reported no change and past‐year alcohol consumption was higher.ConclusionThe rapid survey using convenience sampling gave similar results on change in drinking as conventional surveys but higher past‐year drinking, suggesting self‐selection effects. Aspects of the pandemic driving alcohol consumption down were equally strong or stronger than those driving it up.     

Financial decision‐making and self‐awareness for financial decision‐making is associated with white matter integrity in older adults

Financial decision‐making (FDM) and awareness of the integrity of one''s FDM abilities (or financial awareness) are both critical for preventing financial mistakes. We examined the white matter correlates of these constructs and hypothesized that the tracts connecting the temporal–frontal regions would be most strongly correlated with both FDM and financial awareness. Overall, 49 healthy older adults were included in the FDM analysis and 44 in the financial awareness analyses. The Objective Financial Competency Assessment Inventory was used to measure FDM. Financial awareness was measured by integrating metacognitive ratings into this inventory and was calculated as the degree of overconfidence or underconfidence. Diffusion tensor imaging data were processed with Tracts Constrained by Underlying Anatomy distributed as part of the FreeSurfer analytic suite, which produced average measures of fractional anisotropy and mean diffusivity in 18 white matter tracts along with the overall tract average. As expected, FDM showed the strongest negative associations with average mean diffusivity measure of the superior longitudinal fasciculus ‐temporal (SLFT; r = −.360, p = .011) and ‐parietal (r = −.351, p = .014) tracts. After adjusting for FDM, only the association between financial awareness and average mean diffusivity measure of the right SLFT (r = .310, p = .046) was significant. Overlapping white matter tracts were involved in both FDM and financial awareness. More importantly, these preliminary findings reinforce emerging literature on a unique role of right hemisphere temporal connections in supporting financial awareness.     

Tracking the psychological and socio‐economic impact of the COVID‐19 pandemic in the UK: A methodological report from Wave 5 of the COVID‐19 Psychological Research Consortium (C19PRC) Study

ObjectivesThe COVID‐19 Psychological Research Consortium (C19PRC) Study was established in March 2020 to monitor the psychological and socio‐economic impact of the pandemic in the UK and other countries. This paper describes the protocol for Wave 5 (March–April 2021).MethodsThe survey assessed: COVID‐19 related experiences; experiences of common mental health disorders; psychological characteristics; and social and political attitudes. Adults who participated in any previous wave (N = 4949) were re‐invited to participate. Weights were calculated using a survey raking algorithm to ensure the longitudinal panel was nationally representative in terms of gender, age, and household income, amongst other factors.ResultsOverall, 2520 adults participated. A total of 2377 adults who participated in the previous survey wave (November–December 2020) were re‐interviewed at Wave 5 (61.5% retention rate). Attrition between these two waves was predicted by younger age, lower household income, children living in the household, and treatment for mental health difficulties. Of the adults recruited into the C19PRC study at baseline, 57.4% (N = 1162) participated in Wave 5. The raking procedure re‐balanced the longitudinal panel to within 1.5% of population estimates for selected socio‐demographic characteristics.ConclusionThis paper outlines the growing strength of the publicly available C19PRC Study data for COVID‐19‐related interdisciplinary research.     

Mixed‐effects multilevel analysis followed by canonical correlation analysis is an effective fMRI tool for the investigation of idiosyncrasies

We report that regions‐of‐interest (ROIs) associated with idiosyncratic individual behavior can be identified from functional magnetic resonance imaging (fMRI) data using statistical approaches that explicitly model individual variability in neuronal activations, such as mixed‐effects multilevel analysis (MEMA). We also show that the relationship between neuronal activation in fMRI and behavioral data can be modeled using canonical correlation analysis (CCA). A real‐world dataset for the neuronal response to nicotine use was acquired using a custom‐made MRI‐compatible apparatus for the smoking of electronic cigarettes (e‐cigarettes). Nineteen participants smoked e‐cigarettes in an MRI scanner using the apparatus with two experimental conditions: e‐cigarettes with nicotine (ECIG) and sham e‐cigarettes without nicotine (SCIG) and subjective ratings were collected. The right insula was identified in the ECIG condition from the χ ²‐test of the MEMA but not from the t‐test, and the corresponding activations were significantly associated with the similarity scores (r = −.52, p = .041, confidence interval [CI] = [−0.78, −0.17]) and the urge‐to‐smoke scores (r = .73, p <.001, CI = [0.52, 0.88]). From the contrast between the two conditions (i.e., ECIG > SCIG), the right orbitofrontal cortex was identified from the χ ²‐tests, and the corresponding neuronal activations showed a statistically meaningful association with similarity (r = −.58, p = .01, CI = [−0.84, −0.17]) and the urge to smoke (r = .34, p = .15, CI = [0.09, 0.56]). The validity of our analysis pipeline (i.e., MEMA followed by CCA) was further evaluated using the fMRI and behavioral data acquired from the working memory and gambling tasks available from the Human Connectome Project.     

Pre‐supplementary motor network connectivity and clinical outcome of magnetic stimulation in obsessive–compulsive disorder

A large proportion of patients with obsessive–compulsive disorder (OCD) respond unsatisfactorily to pharmacological and psychological treatments. An alternative novel treatment for these patients is repetitive transcranial magnetic stimulation (rTMS). This study aimed to investigate the underlying neural mechanism of rTMS treatment in OCD patients. A total of 37 patients with OCD were randomized to receive real or sham 1‐Hz rTMS (14 days, 30 min/day) over the right pre‐supplementary motor area (preSMA). Resting‐state functional magnetic resonance imaging data were collected before and after rTMS treatment. The individualized target was defined by a personalized functional connectivity map of the subthalamic nucleus. After treatment, patients in the real group showed a better improvement in the Yale–Brown Obsessive Compulsive Scale than the sham group (F _1,35 = 6.0, p = .019). To show the neural mechanism involved, we identified an “ideal target connectivity” before treatment. Leave‐one‐out cross‐validation indicated that this connectivity pattern can significantly predict patients'' symptom improvements (r = .60, p = .009). After real treatment, the average connectivity strength of the target network significantly decreased in the real but not in the sham group. This network‐level change was cross‐validated in three independent datasets. Altogether, these findings suggest that personalized magnetic stimulation on preSMA may alleviate obsessive–compulsive symptoms by decreasing the connectivity strength of the target network.     

Long‐term functional prognosis and related factors of spinal cord stimulation in patients with disorders of consciousness

IntroductionThe treatment of patients with disorders of consciousness (DoC) remains a challenging issue, and spinal cord stimulation (SCS) has been reported to be a promising treatment for DoC in some studies.AimsThis study explores the efficiency of SCS in treating patients with DoC at different consciousness levels, including the vegetative state/unresponsive wakefulness syndrome (VS/UWS) and the minimally conscious state (MCS) and summarizes and analyzes the long‐term effect and related factors of SCS in patients with DoC.ResultsAn overall positive outcome was reached in 35 of 110 patients (31.8%). Among patients with positive outcomes, the MCS group improved 45.53% more than VS/UWS group, and this difference was statistically significant. In terms of the recommendation standard, positive outcomes occurred in 33 patients (94.3%) in the highly recommended group and 2 patients (5.7%) in the weakly recommended group (p < 0.001). After adjustment for potential covariables, young age (age ≤ 19 years old) (p = 0.045) and MCS (p < 0.001) were significantly correlated with positive outcome. A nomogram based on age, state of consciousness, and pathogeny showed good predictive performance, with a c‐index of 0.794. The Hosmer–Lemeshow goodness‐of‐fit test showed that the model was well calibrated (χ ² = 3.846, p = 0.871).ConclusionsSCS is one of the most feasible treatments for patients with DoC, especially for patients with MCS. Younger age is significantly associated with better outcomes and could therefore serve as a basis for preoperative screening. However, more evidence‐based randomized controlled trials are needed to confirm the efficacy of the treatment.     

RAR‐related orphan receptor A: One gene with multiple functions related to migraine

AimsRAR‐related orphan receptor (RORA) involves in regulation of several biological processes including inflammation and circadian rhythm that probably are involved in migraine pathophysiology. In the current study, the association between RORA rs11639084 and rs4774388 variants and susceptibility to migraine were investigated in a sample of Iranian migraine patients for the first time.MethodsIn a case‐control study including 400 participants, 200 migraineurs and 200 healthy controls, genotyping of RORA rs4774388 and rs11639084 polymorphisms was performed using tetra‐primer amplification refractory mutation system–polymerase chain reaction (TP‐ARMS‐PCR).ResultsThe distribution of rs4774388 C/T and T/T genotypes differed significantly between the studied groups. Moreover, an association was observed between rs4774388 and migraine under the recessive mode of inheritance (P = 0.002; OR = 1.89.; CI = 1.25‐2.87). The distribution of rs11639084 alleles and genotypes was not significantly different between migraineurs and healthy controls.ConclusionCurrent results suggest RORA, as a molecular link, may explain inflammation and circadian rhythm dysfunction in migraine. Further studies in different ethnicities are required to confirm the function of RORA in migraine development.     

18F‐fluorodeoxy‐glucose positron emission tomography pattern and prognostic predictors in patients with anti‐GABAB receptor encephalitis

AimsTo identify the metabolic pattern and prognostic predictors in anti‐gamma‐aminobutyric‐acid B (GABAB) receptor encephalitis using ¹⁸F‐fluorodeoxy‐glucose positron emission tomography (¹⁸F‐FDG‐PET).MethodsTwenty‐one patients diagnosed anti‐GABAB receptor encephalitis who underwent ¹⁸F‐FDG‐PET at first hospitalization were retrospectively reviewed. ¹⁸F‐FDG‐PET images were analyzed in comparison with controls. Further group comparisons of ¹⁸F‐FDG‐PET data were carried out between prognostic subgroups.Results ¹⁸F‐FDG‐PET was abnormal in 81% patients with anti‐GABAB receptor encephalitis and was more sensitive than MRI (81% vs. 42.9%, p = 0.025). Alter limbic lobe glucose metabolism (mostly hypermetabolism) was observed in 14 patients (66.7%), of whom 10 (10/14, 71.4%) demonstrated hypermetabolism in the medial temporal lobe (MTL). Group analysis also confirmed MTL hypermetabolism in association with relative frontal and parietal hypometabolism was a general metabolic pattern. After a median follow‐up of 33 months, the group comparisons revealed that patients with poor outcome demonstrated increased metabolism in the MTL compared to those with good outcome.Conclusion ¹⁸F‐FDG‐PET may be more sensitive than MRI in the early diagnosis of anti‐GABAB receptor encephalitis. MTL hypermetabolism was associated with relative frontal or parietal hypometabolism and may serve as a prognostic biomarker in anti‐GABAB receptor encephalitis.     

Factors predicting relapse and treatment discontinuation with paliperidone 3-monthly long-acting injection: A 2-year naturalistic follow-up study

BackgroundPaliperidone 3-monthly (PP3M) long-acting injection has proven efficacy and effectiveness in schizophrenia. Little is known of its effectiveness in other diagnoses.MethodsAll patients starting PP3M were followed up for 2 years. Main outcome measures were relapse and discontinuation from PP3M. Post hoc we examined outcomes in those switched back to one monthly paliperidone (PP1M) long-acting injection.ResultsOverall, 186 patients were followed-up. At the 2-year end point, 110 patients (59%) were still receiving PP3M, and 129 (70%) were receiving some form of paliperidone long-acting injection. Discontinuation from paliperidone long-acting injections (PPLAIs) was more likely with a nonschizophrenia diagnosis (hazard ratio [HR] for continuation 0.429 [95% confidence intervals (CI) – 0.21, 0.87 p = 0.018)), and prior clozapine use [in PP3M patients; HR for discontinuation 1.87 [95% CI – 1.05, 3.30 p = 0.032]). Relapse occurred in 20 (11%) of those receiving PP3M. Relapse on PP3M and PPLAIs was more likely in nonschizophrenia diagnosis (HR 0.17 for remaining relapse-free [95% CI – 0.06, 0.50; p = 0.001]; HR 0.21 [95% CI – 0.08, 0.58 p = 0.002], respectively), polypharmacy in PP3M patients (HR for relapse 7.91 [95% CI – 3.73, 22.9; p < 0.001]) and PPLAI patients (HR for relapse 6.45 [95% CI – 2.49, 16.5; p < 0.001]), and prior clozapine use in PP3M patients (HR for relapse 6.11 [95% CI – 1.82, 20.5; p = 0.003]) and PPLAI patients (HR for relapse 4.52 (95% CI – 1.51, 13.5; p = 0.007).ConclusionsOutcomes with PP3M are excellent in practice, even when used outside its formal license. PP3M was relatively more effective in those with an F20 schizophrenia diagnosis and in those never before considered for or prescribed clozapine.     

Automated machine learning‐based model predicts postoperative delirium using readily extractable perioperative collected electronic data

ObjectivePostoperative delirium (POD) is a common postoperative complication that is relevant to poor outcomes. Therefore, it is critical to find effective methods to identify patients with high risk of POD rapidly. Creating a fully automated score based on an automated machine‐learning algorithm may be a method to predict the incidence of POD quickly.Materials and methodsThis is the secondary analysis of an observational study, including 531 surgical patients who underwent general anesthesia. The least absolute shrinkage and selection operator (LASSO) was used to screen essential features associated with POD. Finally, eight features (age, intraoperative blood loss, anesthesia duration, extubation time, intensive care unit [ICU] admission, mini‐mental state examination score [MMSE], Charlson comorbidity index [CCI], postoperative neutrophil‐to‐lymphocyte ratio [NLR]) were used to established models. Four models, logistic regression, random forest, extreme gradient boosted trees, and support vector machines, were built in a training set (70% of participants) and evaluated in the remaining testing sample (30% of participants). Multivariate logistic regression analysis was used to explore independent risk factors for POD further.ResultsModel 1 (logistic regression model) was found to outperform other classifier models in testing data (area under the curve [AUC] of 80.44%, 95% confidence interval [CI] 72.24%–88.64%) and achieve the lowest Brier Score as well. These variables including age (OR = 1.054, 95%CI: 1.017~1.093), extubation time (OR = 1.027, 95%CI: 1.012~1.044), ICU admission (OR = 2.238, 95%CI: 1.313~3.793), MMSE (OR = 0.929, 95%CI: 0.876~0.984), CCI (OR = 1.197, 95%CI: 1.038~1.384), and postoperative NLR (OR = 1.029, 95%CI: 1.002~1.057) were independent risk factors for POD in this study.ConclusionsWe have built and validated a high‐performing algorithm to demonstrate the extent to which patient risk changes of POD during the perioperative period, thus leading to a rational therapeutic choice.     

Stress hyperglycemia is associated with in‐hospital mortality in patients with diabetes and acute ischemic stroke

Background and ObjectiveStress hyperglycemia may occur in diabetic patients with acute severe cerebrovascular disease, but the results regarding its association with stroke outcomes are conflicting. This study aimed to examine the association between stress‐induced hyperglycemia and the occurrence of in‐hospital death in patients with diabetes and acute ischemic stroke.Research Design and MethodsAll data were from the Chinese Stroke Center Alliance (CSCA) database and were collected between 2016 and 2018 from >300 centers across China. Patients’ demographics, clinical presentation, and laboratory data were extracted from the database. The primary endpoint was in‐hospital death. The ratio of fasting blood glucose (FBG) to HbA1c was calculated, that is, the stress‐induced hyperglycemia ratio (SHR), to determine stress hyperglycemia following acute ischemic stroke.ResultsA total of 168,381 patients were included. The mean age was 66.2 ± 10.7, and 77,688 (43.0%) patients were female. The patients were divided into two groups: survivors (n = 167,499) and non‐survivors (n = 882), as well as into four groups according to their SHR quartiles (n = 42,090–42,099/quartile). There were 109 (0.26%), 142 (0.34%), 196 (0.47%), and 435 (1.03%) patients who died in the Q1, Q2, Q3, and Q4 quartiles, respectively. Compared with Q1 patients, the death risk was higher in Q4 patients (odds ratio (OR) = 4.02) (adjusted OR = 1.80, 95% confidence interval [CI] = 1.10–2.92, p = 0.018 after adjustment for traditional cardiovascular risk factors). The ROC analyses showed that SHR (AUC = 0.667, 95% CI: 0.647–0.686) had a better predictive value for mortality than that of fasting blood glucose (AUC = 0.633, 95% CI: 0.613–0.652) and HbA1c (AUC = 0.523, 95% CI: 0.504–0.543).ConclusionsThe SHR may serve as an accessory parameter for the prognosis of patients with diabetes after acute ischemic stroke. Hyperglycemia in stroke patients with diabetes mellitus is associated with a higher risk of in‐hospital death.     

Amyloid‐β protein and MicroRNA‐384 in NCAM‐Labeled exosomes from peripheral blood are potential diagnostic markers for Alzheimer's disease

ObjectiveWe aimed to establish a method to determine whether amyloid‐β (Aβ) protein and miR‐384 in peripheral blood neural cell adhesion molecule (NCAM)/ATP‐binding cassette transporter A1 (ABCA1) dual‐labeled exosomes may serve as diagnostic markers for the diagnosis of Alzheimer''s disease (AD).MethodsThis was a multicenter study using a two‐stage design. The subjects included 45 subjective cognitive decline (SCD) patients, 50 amnesic mild cognitive impairment (aMCI) patients, 40 AD patients, and 30 controls in the discovery stage. The results were validated in the verification stage in 47 SCD patients, 45 aMCI patients, 45 AD patients, and 30 controls. NCAM single‐labeled and NCAM/ABCA1 double‐labeled exosomes in the peripheral blood were captured and detected by immunoassay.ResultsThe Aβ42, Aβ_42/40, Tau, P‐T181‐tau, and miR‐384 levels in NCAM single‐labeled and NCAM/ABCA1 double‐labeled exosomes of the aMCI and AD groups were significantly higher than those of the SCD, control, and vascular dementia (VaD) groups (all p < 0.05). The Aβ42 and miR‐384 levels in NCAM/ABCA1 dual‐labeled exosomes of the aMCI and AD groups were higher than those of the control and VaD groups (all p < 0.05). The exosomal Aβ42, Aβ_42/40, Tau, P‐T181‐tau, and miR‐384 levels in peripheral blood were correlated with those in cerebrospinal fluid (all p < 0.05).ConclusionThis study, for the first time, established a method that sorts specific surface marker exosomes using a two‐step immune capture technology. The plasma NCAM/ABCA1 dual‐labeled exosomal Aβ_42/40 and miR‐384 had potential advantages in the diagnosis of SCD.