Multi-organ involvement caused by Scedosporium apiospermum infection after near drowning: a case report and literature review.

BACKGROUND: Scedosporium apiospermum (S. apiospermum) is a rare fungal pathogen that causes disseminated infections. It rarely affects immunocompetent individuals and has a poor prognosis. CASE PRESENTATION: A 37-year-old woman presented with multiple lesions in the lungs, brain, and eyes, shortly after near drowning in a car accident. The primary symptoms were chest tightness, limb weakness, headache, and poor vision in the left eye. S. apiospermum infection was confirmed by metagenomic next-generation sequencing (mNGS) of intracranial abscess drainage fluid, although intracranial metastases were initially considered. After systemic treatment with voriconazole, her symptoms improved significantly; however, she lost vision in her left eye due to delayed diagnosis. CONCLUSION: While S. apiospermum infection is rare, it should be considered even in immunocompetent patients. Prompt diagnosis and treatment are essential. Voriconazole may be an effective treatment option.

Mismatch of MRI White Matter Hyperintensities and Gait Function in Patients With Cerebral Small Vessel Disease.

BACKGROUND: Cerebral small vessel disease (CSVD) is closely related to gait disorders. Previous studies have found a negative correlation between the severity of MRI white matter hyperintensities (WMH) and gait speed. However, not every individual with WMH experiences a gait disorder. PURPOSE: To investigate the mechanisms underlying the mismatch between the severity of MRI WMH and gait impairment, in particular in subjects with severe WMH (Fazekas 3, scale 0-3) resulting from vascular disease. STUDY TYPE: Cohort. POPULATION: 54 subjects with severe WMH and gait disorder (WMH-GD; 29 males) and 114 subjects with severe WMH with no gait disorder (WMH-nGD; 60 males). FIELD STRENGTH/SEQUENCE: 3T/diffusion tensor imaging (DTI), and T1-weighted, T2-weighted, FLAIR, DWI, SWI. ASSESSMENT: Trace-based spatial statistics analysis (TBSS) approach (fractional anisotropy, FA; mean diffusivity; radial diffusivity; axial diffusivity); Cognitive assessment; Conventional MRI markers of CSVD (WMH, enlarged perivascular spaces, lacunae, and cerebral microbleeds); Gait parameters (gait speed; cadence; stride length; gait cycle duration; step duration; time-up-and-go test, TUG). Gait disorder was defined as a TUG time exceeding 12 sec. STATISTICAL TESTS: The t-tests, Mann-Whitney U tests, Chi-square tests, and partial correlation analysis (Pearson or Spearman) were used. P < 0.05 with threshold-free cluster enhancement corrected was considered statistically significant for TBSS. RESULTS: After adjusting for age, sex, height, and other conventional MRI markers of CSVD, the WMH-nGD group showed significantly decreased FA values in the corpus callosum, bilateral superior longitudinal fasciculus, left corona radiata, and left posterior thalamic radiation. There was a significant association between FA values and TUG time, gait speed, and stride length in multiple WM tracts, independent of other conventional CSVD markers. DATA CONCLUSION: This study provides evidence for microstructural damage of specific fibers in WMH-GD subjects compared to WMH-nGD subjects. This may explain the mismatch between WMH and gait impairment in subjects with severe WMH. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 3.

Asymmetry of Lacunae between Brain Hemispheres Is Associated with Atherosclerotic Occlusions of Middle Cerebral Artery.

Cerebral small vessel disease (CSVD) commonly coexists with intracranial atherosclerotic stenosis (ICAS). Previous studies have tried to evaluate the relationship between ICAS and CSVD; however, they have yielded varied conclusions. Furthermore, the methodology of these studies is not very rigorous, as they have evaluated the association between ICAS and CSVD of bilateral hemispheres rather than the affected hemisphere. Unilateral middle cerebral artery atherosclerotic occlusion (uni-MCAO) is a favorable model to solve this problem. MATERIAL AND METHODS: Patients with uni-MCAO were retrospectively observed. Imaging characteristics, including lacunae, white matter hyperintensities (WMH), enlarged perivascular spaces (EPVS), and cerebral microbleeds (CMBs), were compared between the hemisphere ipsilateral to the MCAO and the contralateral hemisphere. RESULTS: A total of 219 patients (median age 57 years; 156 males) were enrolled. Compared with the contralateral side, increased quality of lacunae (median, IQR, 0, 2 vs. 0, 1; p < 0.001) and elevated CSVD score (median, IQR, 0, 1 vs. 0, 1; p = 0.004) were found in the occluded hemisphere. No significant differences were shown for WMH, EPVS, and CMBs. CONCLUSIONS: Uni-MCAO has a higher prevalence of lacunae in the ipsilateral hemisphere. However, no interhemispheric differences in WMH, EPVS, or CMBs were found.

Effect of PCSK9 inhibition in combination with statin therapy on intracranial atherosclerotic stenosis: A high-resolution MRI study.

Introduction: Intracranial atherosclerotic stenosis (ICAS) is a common cause of stroke worldwide. Evolocumab, a proprotein convertase subtilisin/kexin type-9 inhibitor (PCSK9i), effectively lowers low-density lipoprotein (LDL) and produces favorable changes in coronary atherosclerosis. This study aimed to determine the effects of PCSK9i on intracranial plaques in moderate-intensity statin-treated individuals with ICAS. Methods: This prospective, observational study monitored the imaging and clinical outcomes of individuals with ICAS who were consecutively treated with moderate-intensity statins with or without PCSK9i. Individuals underwent monthly visits and repeat high-resolution MRI (HR-MRI) at week 12. The primary outcome was a change in HR-MRI after 12 weeks of treatment and the secondary outcome was major vascular events during follow-up. Results: Forty-nine individuals were studied (PCSK9i group: 26 individuals with 28 abnormal vascular regions; statin group: 23 with 27 regions). The PCSK9i group showed a significant reduction in the normalized wall index (0.83 vs. 0.86, p = 0.028) and stenosis degree (65.5 vs. 74.2%, p = 0.01). Similarly, a greater percentage of individuals with a good response to the efficacy of treatment were treated in the PCSK9i group than that in the statin group (75 vs. 44.4%, p = 0.021). The incidence of major vascular events was overall similar between the groups. The treatment options (OR = 8.441, p = 0.01) and prior diabetes (OR = 0.061, p = 0.001) were significantly associated with the efficacy of treatment. Discussion: Statin and PCSK9i combination treatment stabilized intracranial atherosclerotic plaques more often compared to statins alone, as documented by HR-MRI. Further study is warranted to determine if combination treatment improves clinical outcomes in ICAS.

Elevated Plasma Oligomeric Amyloid ß-42 Is Associated with Cognitive Impairments in Cerebral Small Vessel Disease.

Due to the heterogeneity of amyloid ß-42 (Aß42) species, the potential correlation between plasma oligomeric Aß42 (oAß42) and cognitive impairments in cerebral small vessel disease (CSVD) remains unclear. Herein, a sandwich ELISA for the specific detection of Aß42 oligomers (oAß42) and total Aß42 (tAß42) was developed based on sequence- and conformation-specific antibody pairs for the evaluation of plasma samples from a Chinese CSVD community cohort. After age and gender matching, 3-Tesla magnetic resonance imaging and multidimensional cognitive assessment were conducted in 134 CSVD patients and equal controls. The results showed that plasma tAß42 and oAß42 levels were significantly elevated in CSVD patients. By regression analysis, these elevations were correlated with the presence of CSVD and its imaging markers (i.e., white matter hyperintensities). Plasma Aß42 tests further strengthened the predictive power of vascular risk factors for the presence of CSVD. Relative to tAß42, oAß42 showed a closer correlation with memory domains evaluated by neuropsychological tests. In conclusion, this sensitive ELISA protocol facilitated the detection of plasma Aß42; Aß42, especially its oligomeric form, can serve as a biosensor for the presence of CSVD and associated cognitive impairments represented by memory domains.

Co-occurrence of polyneuritis crainials and visual impairment: a case report and literature review.

BACKGROUND: Polyneuritis cranialis (PNC) with the disease characteristics of Guillain-Barré syndrome (GBS) in addition to both ocular and bulbar weakness in the absence of limb paralysis or ataxia is defined as an unusual variant of GBS. As evidence of central nervous system (CNS) involvement, visual impairment is an unusual finding complicating with GBS spectrum disorders and has never been reported in patients with PNC. METHODS: We describe a very rare case who clinically presented with progressive multiple cranial nerve palsy and visual impairment. Furthermore, a literature search of concurrent GBS and optic neuritis (ON) as well as PNC attributed to GBS was conducted. RESULTS: A diagnosis of PNC was considered due to the typical clinical characteristics as well as the presence of cerebrospinal fluid cytoalbumin dissociation and serum antibodies against gangliosides. The clinical manifestations and the bilateral optic nerve involvement in brain magnetic resonance imaging further suggested possible optic neuritis (ON). The patient received treatment with intravenous immunoglobulin followed by short-term use of corticosteroids and finally achieved a full recovery. Thirty-two previously reported cases (17 women, mean age 40) of concurrent GBS and ON and 20 cases of PNC (5 women, mean age 40) were analyzed. We further provided a comprehensive discussion on the potential etiologies, clinical features, therapeutic strategies, and prognosis. CONCLUSIONS: This rare case with the co-occurrence of PNC and visual impairment and the related literature review may help clinicians advance the understanding of GBS spectrum disorders and make appropriate diagnoses and treatment decisions for the rare variants and CNS complications of GBS.

Prevalence and risk factors of stroke in China: a national serial cross-sectional study from 2003 to 2018.

Stroke imposes a substantial burden worldwide. With the rapid economic and lifestyle transition in China, trends of the prevalence of stroke across different geographic regions in China remain largely unknown. Capitalizing on the data in the National Health Services Surveys (NHSS), we assessed the prevalence and risk factors of stroke in China from 2003 to 2018. In this study, data from 2003, 2008, 2013, and 2018 NHSS were collected. Stroke cases were based on participants' self-report of a previous diagnosis by clinicians. We estimated the trends of stroke prevalence for the overall population and subgroups by age, sex, and socioeconomic factors, then compared across different geographic regions. We applied multivariable logistic regression to assess associations between stroke and risk factors. The number of participants aged 15 years or older were 154,077, 146,231, 230,067, and 212,318 in 2003, 2008, 2013, and 2018, respectively, among whom, 1435, 1996, 3781, and 6069 were stroke patients. The age and sex standardized prevalence per 100,000 individuals was 879 in 2003, 1100 in 2008, 1098 in 2013, and 1613 in 2018. Prevalence per 100,000 individuals in rural areas increased from 669 in 2003 to 1898 in 2018, while urban areas had a stable trend from 1261 in 2003 to 1365 in 2018. Across geographic regions, the central region consistently had the highest prevalence, but the western region has an alarmingly increasing trend from 623/100,000 in 2003 to 1898/100,000 in 2018 (P trend<0.001), surpassing the eastern region in 2013. Advanced age, male sex, rural area, central region, hypertension, diabetes, depression, low education and income level, retirement or unemployment, excessive physical activity, and unimproved sanitation facilities were significantly associated with stroke. In conclusion, the increasing prevalence of stroke in China was primarily driven by economically underdeveloped regions. It is important to develop targeted prevention programs in underdeveloped regions. Besides traditional risk factors, more attention should be paid to nontraditional risk factors to improve the prevention of stroke.

Development and external evaluation of predictions models for mortality of COVID-19 patients using machine learning method.

To predict the mortality of patients with coronavirus disease 2019 (COVID-19). We collected clinical data of COVID-19 patients between January 18 and March 29 2020 in Wuhan, China . Gradient boosting decision tree (GBDT), logistic regression (LR) model, and simplified LR were built to predict the mortality of COVID-19. We also evaluated different models by computing area under curve (AUC), accuracy, positive predictive value (PPV), and negative predictive value (NPV) under fivefold cross-validation. A total of 2924 patients were included in our evaluation, with 257 (8.8%) died and 2667 (91.2%) survived during hospitalization. Upon admission, there were 21 (0.7%) mild cases, 2051 (70.1%) moderate case, 779 (26.6%) severe cases, and 73 (2.5%) critically severe cases. The GBDT model exhibited the highest fivefold AUC, which was 0.941, followed by LR (0.928) and LR-5 (0.913). The diagnostic accuracies of GBDT, LR, and LR-5 were 0.889, 0.868, and 0.887, respectively. In particular, the GBDT model demonstrated the highest sensitivity (0.899) and specificity (0.889). The NPV of all three models exceeded 97%, while their PPV values were relatively low, resulting in 0.381 for LR, 0.402 for LR-5, and 0.432 for GBDT. Regarding severe and critically severe cases, the GBDT model also performed the best with a fivefold AUC of 0.918. In the external validation test of the LR-5 model using 72 cases of COVID-19 from Brunei, leukomonocyte (%) turned to show the highest fivefold AUC (0.917), followed by urea (0.867), age (0.826), and SPO2 (0.704). The findings confirm that the mortality prediction performance of the GBDT is better than the LR models in confirmed cases of COVID-19. The performance comparison seems independent of disease severity. Supplementary Information: The online version contains supplementary material available at(10.1007/s00521-020-05592-1).

Universal health coverage in China: a serial national cross-sectional study of surveys from 2003 to 2018.

BACKGROUND: Achieving universal health coverage (UHC) is one crucial target of the Sustainable Development Goals. However, consistent trends data for UHC evaluation in China are still scarce. The aim of our study was to provide a comprehensive assessment of UHC in China. METHODS: In this serial cross-sectional study, we collected nationally representative data from the latest four rounds (2003, 2008, 2013, and 2018) of the National Health Service Surveys, with the aim of evaluating UHC in China. These surveys used multistage stratified cluster sampling covering all 31 provinces, autonomous regions, and municipalities in mainland China. Within each household, all members aged 15 years and older were interviewed. For children and adolescents aged younger than 15 years, their adult family members answered the questions for them. We constructed a UHC index following the WHO-recommended framework that included service coverage (nine prevention indicators and five treatment indicators) and financial protection (three indicators) dimensions. Bayesian regression models were done to investigate the trends in and projections of UHC index and indicators, with average annual percentage change (AAPC) and probabilities of achieving the 2030 WHO targets. Based on trends and projections, we counted population equivalents with UHC coverage. To examine the potential efficiency of financial investment, we quantified UHC performance based on government health expenditure (GHE) per capita. Finally, we explored the association between each UHC indicator and macroeconomic and health systems characteristics by using multiple regression. FINDINGS: We sampled 57 023 households from 95 counties between September and October, 2003; 56 456 households from 94 counties between June and July, 2008; 93 613 households from 156 counties between August and October, 2013; and 94 076 households from 156 counties in September, 2018. A total of 901 182 individuals were involved in this study (193 689 in 2003, 177 501 in 2008, 273 688 in 2013, and 256 304 in 2018). Although the overall UHC increased from 44·0% (95% CI 43·0-44·9) in 2003 to 79·8% (79·2-80·3) in 2018 and is predicted to meet the 80% global target by 2030, the progress towards UHC has steadily slowed down nationally. Based on current projections, an estimated 105·8 (95% CI 27·3-189·1) million population equivalents would still not have UHC coverage in 2030. The treatment index showed a large increase over time from 2003 to 2018 (AAPC 4·9%, 2·9-7·2), with minimal disparities and all subgroups will achieve the target in the treatment domain by 2030 (possibilities higher than 90%). However, the prevention index presented poor performance with a small increase over time from 2003 to 2018 (AAPC 1·4%, 0·3-2·5) and sizable disparities across regions, urban-rural areas, and income (all p<0·0001). To achieve at least 80% UHC coverage, provinces would need to reach at least ¥445 in GHE per capita per year under maximum efficiency. However, large gaps between the observed and frontier UHC index, especially in several western provinces, indicated inefficiency. Furthermore, we found that primary health-care institutions were closely and positively related to UHC indicators especially in the prevention domain. INTERPRETATION: Although considerable achievements have been made, the progress towards UHC is not keeping pace with the rapid society development in China. Considering an increased burden in non-communicable diseases and an ageing population, prioritising the efficacy of financial investment and optimising resource allocation by strengthening primary health care are necessary to achieve UHC in China. FUNDING: National Natural Science Foundation of China and National Health Commission of the People's Republic of China.

Automatic segmentation of white matter hyperintensities in routine clinical brain MRI by 2D VB-Net: A large-scale study.

White matter hyperintensities (WMH) are imaging manifestations frequently observed in various neurological disorders, yet the clinical application of WMH quantification is limited. In this study, we designed a series of dedicated WMH labeling protocols and proposed a convolutional neural network named 2D VB-Net for the segmentation of WMH and other coexisting intracranial lesions based on a large dataset of 1,045 subjects across various demographics and multiple scanners using 2D thick-slice protocols that are more commonly applied in clinical practice. Using our labeling pipeline, the Dice consistency of the WMH regions manually depicted by two observers was 0.878, which formed a solid basis for the development and evaluation of the automatic segmentation system. The proposed algorithm outperformed other state-of-the-art methods (uResNet, 3D V-Net and Visual Geometry Group network) in the segmentation of WMH and other coexisting intracranial lesions and was well validated on datasets with thick-slice magnetic resonance (MR) images and the 2017 medical image computing and computer assisted intervention WMH Segmentation Challenge dataset (with thin-slice MR images), all showing excellent effectiveness. Furthermore, our method can subclassify WMH to display the WMH distributions and is very lightweight. Additionally, in terms of correlation to visual rating scores, our algorithm showed excellent consistency with the manual delineations and was overall better than those from other competing methods. In conclusion, we developed an automatic WMH quantification framework for multiple application scenarios, exhibiting a promising future in clinical practice.

Arterial Tortuosity and Its Correlation with White Matter Hyperintensities in Acute Ischemic Stroke.

Introduction: The association between arterial tortuosity and acute ischemic stroke (AIS) has been reported, but showing inconsistent results. We hypothesized that tortuosity of extra- and intracranial large arteries might be higher in AIS patients. Furthermore, we explored the correlation between artery tortuosity and white matter hyperintensity (WMH) severity in AIS patients. Methods: 166 AIS patients identified as large artery atherosclerosis, and 83 control subjects were enrolled. All subjects received three-dimensional computed tomography angiography (CTA). Arterial tortuosity was evaluated using the tortuosity index. WMHs were evaluated using magnetic resonance imaging in all AIS patients. Results: AIS patients showed significantly increased arterial tortuosity index relative to controls, including left carotid artery (CA) (p = 0.001), right CA (p < 0.001), left common carotid artery (CCA) (p < 0.001), right CCA (p < 0.001), left internal carotid artery (p = 0.001), right internal carotid artery (p = 0.01), left extracranial internal carotid artery (EICA) (p < 0.001), right EICA (p = 0.01), and vertebral artery dominance (VAD) (p = 0.001). The tortuosity of all above arteries was associated with the presence of AIS. AIS patients with moderate or severe WMHs had a higher tortuosity index in left CA (p = 0.005), left CCA (p = 0.003), left EICA (p = 0.07), and VAD (p = 0.001). In addition, the tortuosity of left EICA and VAD was associated with WMH severity in AIS patients. Conclusions: Increased extra- and intracranial large arteries tortuosity is associated with AIS. The tortuosity of left carotid artery system and vertebral artery may be the independent risk factors for WMH severity in AIS patients. Clinical Trial Registration. This trial is registered with NCT03122002 (http://www.clinicaltrials.gov).

Triglyceride-Glucose Index and the Risk of Stroke: A Systematic Review and Dose-Response Meta-Analysis.

Insulin resistance (IR) is an independent risk factor of cardiovascular disease. Recent research has proposed a new inexpensive and reliable indicator of IR: triglyceride glucose index (TyG index). We aim to evaluate the dose-response association between the TyG index and stroke through meta-analysis. Literature published from inception until October 2021 were searched in PubMed, Embase, Cochrane Library and Web of science. Cohort studies published in English and focusing on the association between the TyG index and stroke were included in our meta-analysis. I2 statistic and Chi-square were used to assess the heterogeneity. When I2≥30% or p≤0.10, the random-effect model was used to pool the effect; otherwise, we chose the fixed-effect model. Eleven cohort studies, including 5 721 077 subjects and 95 490 stroke patients, were included in our study. After pooling the effect adjusted by multiple confounders, we found that compared with the lowest baseline TyG index group, the highest one was independently associated with increased stroke risk (RR: 1.27; 95% CI, 1.24 to 1.29; I2=6%). Dose-response meta-analysis showed that the association between the two variables had a non-linear trend (p-nonlinearity<0.0001; p-heterogeneity=0.28). Subgroup analysis showed that the risk of ischemic stroke was positively correlated with TyG index (RR: 1.48; 95% CI, 1.34 to 1.62; I2=15%), while we did not observe this correlation in hemorrhagic stroke patients. In patients with type 2 diabetes and acute coronary syndrome, the TyG index was linearly correlated with incident strokes. In conclusion, elevated TyG index is the independent risk factor for incident strokes (especially ischemic stroke).

Intravenous Alteplase in a Patient With Acute Ischemic Stroke Subsequent to Purulent Meningitis: A Case Report and Literature Review.

This report highlights the outcome of intravenous alteplase in a patient with acute ischemic stroke subsequent to purulent meningitis. This type of meningitis has not been defined in the guideline for early treatment of acute ischemic stroke. A 58-year-old woman with purulent meningitis developed a sudden stroke and was admitted to our emergency department. She received 0.6 mg/kg of alteplase intravenously 90 minutes after stroke onset. At 1 hour after thrombolysis, the patient's National Institute of Health Stroke Scale score improved from 9 to 4. At 2 hours, she developed a sudden severe headache that progressed to coma, and her National Institute Health Stroke Scale score rapidly deteriorated to 20. Cranial computed tomography revealed subarachnoid hemorrhage and multiple bilateral lobar brain hemorrhages. She died of a cerebellar tonsillar hernia. Intravenous alteplase might be hazardous in patients with acute ischemic stroke subsequent to purulent meningitis.

Low serum lipid levels, use of statin and cerebral microbleeds: A systematic review and meta-analysis.

INTRODUCTION: Previous studies have shown that low serum lipids and statins may be related to cerebral hemorrhage. We made the meta-analysis to evaluate the associations between serum lipid levels or statins treatment and cerebral microbleeds (CMBs) to identify whether the similar correlation also existed. METHOD: We comprehensively searched the Medline, Embase, Cochrane library, Web of Science, only included English journal articles, and systematically collected the observational studies and randomized controlled trials (RCTs) from September 1975 to August 2021. Random-effects model was used to pool data. Statistical heterogeneity was assessed by I2 statistic and chi-square. 11 items checklists recommended by the Agency for Healthcare Research and Quality (AHRQ), Newcastle-Ottawa Scale (NOS), and Cochrane Risk of Bias tool (ROB) were used to evaluate the methodological quality of cross-sectional studies, cohort studies and randomized controlled trial, respectively. RESULTS: Five cohort studies, two RCTs, and ten cross-sectional studies, including 16,637 subjects and 2663 CMBs patients, were included in our quantitative synthesis. Our study found that after adjusting the covariates, total cholesterol (TC) was significantly inversely correlated with the prevalent CMBs in any location, while total triglycerides (TG) and High-density lipoprotein (HDL) were significantly inversely associated with prevalent deep CMBs. Low-density lipoprotein (LDL) was negatively associated with incident CMBs after adjusted confounders. We did not found statistical differences between statin and CMBs after adjusted covariates. CONCLUSION: Serum major lipid (TC TG HDL LDL) levels may be inversely associated with CMBs. Currently, no sufficient evidence proves that statin therapy is the risk factor of CMBs.

Hemorrhagic transformation after acute ischemic stroke caused by polycythemia vera: Report of two case.

BACKGROUND: Polycythemia vera (PV) is a chronic myeloproliferative disorder characterized by an increase in red blood cells in the peripheral blood. Previous work has reported the occurrence of thrombosis or hemorrhage arising in the cerebral vasculature secondary to PV. However, hemorrhagic transformation after PV-associated acute ischemic stroke has not been previously described. CASE SUMMARY: We herein present two cases of PV where hemorrhagic transformation occurred after an acute ischemic stroke. Case 1 was a 57-year-old woman with a history of hypertension who was admitted for left-sided weakness. Case 2 was a 68-year-old man who was admitted for a 10-d sudden left arm weakness. Imaging examinations for the two patients revealed hemorrhagic transformation after acute ischemic stroke. Both patients had JAK-2-V617F mutation and received antiplatelet therapy. Both of them had a good prognosis during the follow-up. CONCLUSION: This report suggested that hemorrhagic transformation may occur in acute ischemic stroke caused by PV. Antiplatelet drugs do not seem to influence the long-term outcomes in such patients. Future research should focus on establishing a standard antiplatelet treatment strategy for this condition.

Immunologic memory to SARS-CoV-2 in convalescent COVID-19 patients at 1 year postinfection.

BACKGROUND: Understanding the complexities of immune memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is key to gain insights into the durability of protective immunity against reinfection. OBJECTIVE: We sought to evaluate the immune memory to SARS-CoV-2 in convalescent patients with longer follow-up time. METHODS: SARS-CoV-2-specific humoral and cellular responses were assessed in convalescent patients with coronavirus disease 2019 (COVID-19) at 1 year postinfection. RESULTS: A total of 78 convalescent patients with COVID-19 (26 moderate, 43 severe, and 9 critical) were recruited after 1 year of recovery. The positive rates of both anti-receptor-binding domain and antinucleocapsid antibodies were 100%, whereas we did not observe a statistical difference in antibody levels among different severity groups. Accordingly, the prevalence of neutralizing antibodies (nAbs) reached 93.59% in convalescent patients. Although nAb titers displayed an increasing trend in convalescent patients with increased severity, the difference failed to achieve statistical significance. Notably, there was a significant correlation between nAb titers and anti-receptor-binding domain levels. Interestingly, SARS-CoV-2-specific T cells could be robustly maintained in convalescent patients, and their number was positively correlated with both nAb titers and anti-receptor-binding domain levels. Amplified SARS-CoV-2-specific CD4+ T cells mainly produced a single cytokine, accompanying with increased expression of exhaustion markers including PD-1, Tim-3, TIGIT, CTLA-4, and CD39, while the proportion of multifunctional cells was low. CONCLUSIONS: Robust SARS-CoV-2-specific humoral and cellular responses are maintained in convalescent patients with COVID-19 at 1 year postinfection. However, the dysfunction of SARS-CoV-2-specific CD4+ T cells supports the notion that vaccination is needed in convalescent patients for preventing reinfection.

Cortical and Subcortical Grey Matter Abnormalities in White Matter Hyperintensities and Subsequent Cognitive Impairment.

Grey matter (GM) alterations may contribute to cognitive decline in individuals with white matter hyperintensities (WMH) but no consensus has yet emerged. Here, we investigated cortical thickness and grey matter volume in 23 WMH patients with mild cognitive impairment (WMH-MCI), 43 WMH patients without cognitive impairment, and 55 healthy controls. Both WMH groups showed GM atrophy in the bilateral thalamus, fronto-insular cortices, and several parietal-temporal regions, and the WMH-MCI group showed more extensive and severe GM atrophy. The GM atrophy in the thalamus and fronto-insular cortices was associated with cognitive decline in the WMH-MCI patients and may mediate the relationship between WMH and cognition in WMH patients. Furthermore, the main results were well replicated in an independent dataset from the Alzheimer's Disease Neuroimaging Initiative database and in other control analyses. These comprehensive results provide robust evidence of specific GM alterations underlying WMH and subsequent cognitive impairment.

Case Report: Clinical and Imaging Characteristics of a Patient with Anti-flotillin Autoantibodies: Neuromyelitis Optica or Multiple Sclerosis?

Background: Demyelination diseases are complex puzzles that are not always straightforward to diagnose. Multiple sclerosis and neuromyelitis optica are two that are frequently encountered. Numerous autoantibodies newly discovered in recent years have significantly aided clinical reasoning and diagnosis in differentiating demyelination disorders. Here we report a case of demyelination disease with anti-flotillin autoantibodies positive, which is not common in past references. Case summary: The patient presented with characteristic neuromyelitis optica symptoms and had remission and relapse. But his images exhibited characteristics of both neuromyelitis optica spectrum illness and multiple sclerosis. Conclusion: This is the first case report describing the clinical course and imaging characteristics of demyelination illness associated with anti-flotillin autoantibodies. Although so far it appears to be a subtype of multiple sclerosis, there is still a potential that it is separate from MS and NMOSD.

Association Between Ischemic Stroke and COVID-19 in China: A Population-Based Retrospective Study.

Background and Purpose: To investigate the effect of prior ischemic stroke on the outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19), and to describe the incidence, clinical features, and risk factors of acute ischemic stroke (AIS) following COVID-19. Methods: In this population-based retrospective study, we included all the hospitalized positive patients with COVID-19 at Wuhan City from December 29, 2019 to April 15, 2020. Clinical data were extracted from administrative datasets coordinated by the Wuhan Health Commission. The propensity score matching and multivariate logistic regression analyses were used to adjust the confounding factors. Results: There are 36,358 patients in the final cohort, in which 1,160 (3.2%) had a prior stroke. After adjusting for available baseline characteristics, patients with prior stroke had a higher proportion of severe and critical illness and mortality. We found for the first time that the premorbid modified Rankin Scale (MRS) grouping (odds ratio [OR] = 1.796 [95% CI 1.334-2.435], p < 0.001) and older age (OR = 1.905 [95% CI 1.211-3.046], p = 0.006) imparted increased risk of death. AIS following COVID-19 occurred in 124 (0.34%) cases, and patients with prior stroke had a much higher incidence of AIS (3.4%). Logistic regression analyses confirmed an association between the severity of COVID-19 with the incidence of AIS. COVID-19 patients with AIS had a significantly higher mortality compared with COVID-19 patients without stroke and AIS patients without COVID-19. Conclusions: Coronavirus disease 2019 patients with prior stroke, especially those with the higher premorbid MRS or aged, have worse clinical outcomes. Furthermore, COVID-19 increases the incidence of AIS, and the incidence is positively associated with the severity of COVID-19.