Background: The complications of coronavirus disease 2019 (COVID-19) involved multiple organs or systems, especially in critically ill patients. We aim to investigate the neurological complications in critically ill patients with COVID-19. Methods: This retrospective single-center case series analyzed critically ill patients with COVID-19 at the intensive care unit of Tongji Hospital, Wuhan, China from February 5 to April 2, 2020. Demographic data, clinical and laboratory findings, comorbidities and treatments were collected and analyzed. Results: Among 86 patients with confirmed COVID-19, 54 patients (62.8%) were male, and the mean (SD) age was 66.6 (11.1) years. Overall, 65% patients presented with at least one neurological symptom. Twenty patients (23.3%) had symptoms involving the central nervous system, including delirium, cerebrovascular diseases and hypoxic-ischemic brain injury, while 6 patients (7%) had neuromuscular involvement. Seven of 86 patients exhibited new stroke and 6 (7%) cases were ischemic. A significantly higher prevalence of antiphospholipid antibodies was observed in patients with ischemic stroke than in those without stroke (83.3 vs. 26.9%, p < 0.05). Patients with ischemic stroke were more likely to have a higher myoglobulin level, and a lower hemoglobin level. Conclusions: The clinical spectrum of neurological complications in critically ill patients with COVID-19 was broad. Stroke, delirium and neuromuscular diseases are common neurological complications of COVID-19. Physicians should pay close attention to neurological complications in critically ill patients with COVID-19.

Background:Autoimmune encephalitis associated with antibodies against γ-aminobutyric acid B receptor (GABAB R) in patients with limbic encephalitis (LE) was first described in 2010. We present a series of Han Chinese patients for further clinical refinement.Methods:Serum and cerebrospinal fluid (CSF) samples from patients referred to the program of encephalitis and paraneoplastic syndrome of Peking Union Medical College Hospital were tested with indirect immunofluorescence. Clinical information of patients with anti-GABAB R antibody positivity was retrospectively reviewed, and descriptive statistical analysis was performed.Results:All eighteen anti-GABAB R antibody-positive cases had limbic syndromes, and electroencephalogram (EEG) or neuroimaging evidence fulfilled the diagnostic criteria of LE. Four patients had additional antibodies against Hu in serum and one had anti-N-methyl-d-aspartate receptor antibody in both sera and CSF. Seventeen (17/18) patients presented with new-onset refractory seizure or status epileptics. Twelve (12/18) patients had memory deficits, 11 (11/18) patients had personality change, 7 (7/18) patients had disturbance of consciousness, and 3 (3/18) patients showed cerebellar dysfunction. One patient with LE had progressive motor and sensory polyneuropathy. Lung cancer was detected in 6 (6/18) patients. Ten (10/18) patients showed abnormality in bilateral or unilateral mediotemporal region on magnetic resonance imaging. Ten (10/18) patients had temporal lobe epileptic activity with or without general slowing on EEG. Seventeen patients received immunotherapy and 15 of them showed neurological improvement. Four patients with lung cancer died within 1–12 months due to neoplastic complications.Conclusions:Our study demonstrates that most Han Chinese patients with anti-GABAB R antibody-associated LE have prominent refractory epilepsy and show neurological improvement on immunotherapy. Patients with underlying lung tumor have a relatively poor prognosis. Testing for anti-GABAB R antibodies is necessary for patients with possible LE or new-onset epilepsy with unknown etiology.

Injury to the spinal cord causes transection of axon fibers and neural cell death, resulting in disruption of the neural network and severe functional loss. Reconstruction of the damaged neural circuits was once considered to be hopeless as the adult mammalian central nervous system has very poor ability to regenerate. For this reason, there is currently no effective therapeutic treatment for spinal cord injury (SCI). However, with recent developments in stem cell research and cell culture technology, regenerative therapy using neural stem cell (NSC) transplantation has rapidly been developed, and this therapeutic strategy makes it possible to rebuild the destroyed neural circuits. In this review, we discuss the recent breakthroughs in NSC transplantation therapy for SCI. Developmental Dynamics 247:75-84,

Purpose: Ischemic vascular diseases, including myocardial infarction (MI) and stroke, have been found to be associated with elevated expression of αvβ3-integrin, which provides a promising target for semi-quantitative monitoring of the disease. For the first time, we employed 68Ga-S-2-(isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid-PEG3-E[c(RGDyK)]2 (68Ga-PRGD2) to evaluate the αvβ3-integrin-related repair in post-MI and post-stroke patients via positron emission tomography/computed tomography (PET/CT).Methods: With Institutional Review Board approval, 23 MI patients (3 days-2 years post-MI) and 16 stroke patients (3 days-13 years post-stroke) were recruited. After giving informed consent, each patient underwent a cardiac or brain PET/CT scan 30 min after the intravenous injection of 68Ga-PRGD2 in a dose of approximately 1.85 MBq (0.05 mCi) per kilogram body weight. Two stroke patients underwent repeat scans three months after the event.Results: Patchy 68Ga-PRGD2 uptake occurred in or around the ischemic regions in 20/23 MI patients and punctate multifocal uptake occurred in 8/16 stroke patients. The peak standardized uptake values (pSUVs) in MI were 1.94 ± 0.48 (mean ± SD; range, 0.62-2.69), significantly higher than those in stroke (mean ± SD, 0.46 ± 0.29; range, 0.15-0.93; P < 0.001). Higher 68Ga-PRGD2 uptake was observed in the patients 1-3 weeks after the initial onset of the MI/stroke event. The uptake levels were significantly correlated with the diameter of the diseases (r = 0.748, P = 0.001 for MI and r = 0.835, P = 0.003 for stroke). Smaller or older lesions displayed no uptake.Conclusions: 68Ga-PRGD2 uptake was observed around the ischemic region in both MI and stroke patients, which was correlated with the disease phase and severity. The different image patterns and uptake levels in MI and stroke patients warrant further investigations.

Together with residual host neurons, transplanted neural stem cell (NSC)-derived neurons play a critical role in reconstructing disrupted neural circuits after spinal cord injury (SCI). Since a large number of tracts are disrupted and the majority of host neurons die around the lesion site as the damage spreads, minimizing this spreading and preserving the lesion site are important for attaining further improvements in reconstruction. High mobility group box-1 (HMGB1) is a damage-associated molecular pattern protein that triggers sterile inflammation after tissue injury. In the ischemic and injured brain, neutralization of HMGB1 with a specific antibody reportedly stabilizes the blood-brain barrier, suppresses inflammatory cytokine expression, and improves functional recovery. Using a SCI model mouse, we here developed a combinatorial treatment for SCI: administering anti-HMGB1 antibody prior to transplantation of NSCs derived from human induced pluripotent stem cells (hiPSC-NSCs) yielded a dramatic improvement in locomotion recovery after SCI. Even anti-HMGB1 antibody treatment alone alleviated blood-spinal cord barrier disruption and edema formation, and increased the number of neurites from spared axons and the survival of host neurons, resulting in functional recovery. However, this recovery was greatly enhanced by the subsequent hiPSC-NSC transplantation, reaching an extent that has never before been reported. We also found that this improved recovery was directly associated with connections established between surviving host neurons and transplant-derived neurons. Taken together, our results highlight combinatorial treatment with anti-HMGB1 antibody and hiPSC-NSC transplantation as a promising novel therapy for SCI. Stem Cells 2018;36:737-750.

BackgroundThis study explored the diagnostic value of a combined modality of Superb Microvascular Imaging (SMI) and shear-wave elastography in differentiating malignant and benign breast lesions.Material/MethodsA total of 121 patients with 123 breast lesions enrolled underwent conventional ultrasound exam (US), Color Doppler Flow Imaging (CDFI), SMI examination, and Virtual Touch Tissue Quantification (VTQ) measurement between May 2016 and October 2017. Vessels were detected by both CDFI and SMI in a quantitative manner. The stiffness of all the breast tissues was evaluated by VTQ method. We further assessed the diagnostic performances of CDFI, SMI, VTQ, CDFI+VTQ, and SMI+VTQ.ResultsBoth CDFI and SMI exhibited significant differences between malignant and benign masses (p<0.001) in terms of Adler classification. The mean shear-wave velocity (SWV) of malignant neoplasms was 5.28 m/s, with interquartile range (IQR) 4.01–6.39 m/s (p<0.001). The mean SWV of benign lesions was 2.64 m/s, with IQR 2.30–5.01 m/s (p<0.001). No significant difference was found for the area under the receiver operating characteristic curve (AUC) for CDFI, SMI, and VTQ (χ2=2.29, P=0.3715). The sensitivity was the highest on SMI+VTQ (85.42%) and the lowest on CDFI (58.33%). CDFI+VTQ (85.33%) had a slightly higher specificity than SMI+VTQ (84.00%). The accuracy rate of these 2 modalities remained the same (84.55%).ConclusionsSuperb Microvascular Imaging yields more detailed vascular information in the bloodstream in benign and malignant breast masses compared with conventional ultrasonography. VTQ provides standardized quantified results in assessing tissue stiffness. The combined modality of SMI+VTQ added to conventional ultrasonography presented a better diagnostic performance in differentiating malignant breast neoplasms.

BackgroundThis study aimed to compare superb microvascular imaging (SMI) with grayscale ultrasound (US) and color Doppler flow imaging (CDFI) to evaluate vascular distribution and morphology to distinguish between benign and malignant thyroid nodules.Material/MethodsSeventy-one patients with 76 thyroid nodules underwent grayscale US, CDFI, and SMI thyroid imaging. CDFI and SMI assessed vascular quantity, morphology, and distribution, and was graded according to Adler’s method, as absent (grade 0), minimal (grade 1), moderate (grade 2), or marked (grade 3). The detection of malignancy was compared between the following imaging groups, grayscale US alone, US combined with CDFI, and US combined with SMI.ResultsSMI was significantly more accurate in identifying malignant thyroid nodules (79.3%) compared with CDFI (55.2%) (P<0.001). In malignant thyroid nodules, penetrating blood vessels were identified by SMI in 62.1% and by CDFI in 41.4%; there was no significant difference in vascular distribution between SMI (P=0.835) and CDFI (P=0.806). Grayscale US with SMI resulted in the greatest diagnostic sensitivity, accuracy, and specificity (86.21%, 85.53%, and 85.11%) compared with grayscale US with CDFI (75.86%, 82.89%, and 87.23%). Receiver operating characteristic (ROC) area under the curve (AUC) values of US with SMI, US with CDFI, and US alone were 0.918 (95% CI, 0.856–0.979), 0.911 (95% CI, 0.849–0.973), and 0.847 (95% CI, 0.762–0.932), respectively (P<0.001).ConclusionsSMI as an adjunct to grayscale US provided significantly more information on vascularity associated with malignancy in thyroid nodules, when compared with grayscale US or with US and CDFI.

Mutation processes differ between types of point mutation, genomic locations, cells, and biological species. For some point mutations, specific neighboring bases are known to be mechanistically influential. Beyond these cases, numerous questions remain unresolved, including: what are the sequence motifs that affect point mutations? How large are the motifs? Are they strand symmetric? And, do they vary between samples? We present new log-linear models that allow explicit examination of these questions, along with sequence logo style visualization to enable identifying specific motifs. We demonstrate the performance of these methods by analyzing mutation processes in human germline and malignant melanoma. We recapitulate the known CpG effect, and identify novel motifs, including a highly significant motif associated with A[Formula: see text]G mutations. We show that major effects of neighbors on germline mutation lie within [Formula: see text] of the mutating base. Models are also presented for contrasting the entire mutation spectra (the distribution of the different point mutations). We show the spectra vary significantly between autosomes and X-chromosome, with a difference in T[Formula: see text]C transition dominating. Analyses of malignant melanoma confirmed reported characteristic features of this cancer, including statistically significant strand asymmetry, and markedly different neighboring influences. The methods we present are made freely available as a Python library https://bitbucket.org/pycogent3/mutationmotif.