BackgroundAnti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a clinically heterogeneous disorder characterized by epileptic seizures, psychosis, dyskinesia, consciousness impairments, and autonomic instability. Symptoms are always various. Sometimes it presents in milder or incomplete forms. We report 4 cases of anti-NMDAR encephalitis with incomplete forms, 3 cases of which were accompanied by neuromyelitis optica spectrum disorder or neurosyphilis respectively.Case presentationA 33-year-old man presented with dysarthria, movement disorder and occasional seizures. He had 6 relapses in 28 years. When suffered from upper respiratory tract syndrome, he developed behavioral and consciousness impairment. Cranial MRI was normal. Viral PCR studies and oncologic work-up were negative. Anti-NMDAR antibody was detected in CSF and serum.A 21-year-old female manifested dizziness and diplopia ten months and six months before, respectively. Both responded to steroid therapy and improved completely. This time she presented with progressive left limb and facial anesthesia, walking and holding unsteadily. Spinal cord MRI follow-up showed abnormality of medulla oblongata and cervical cord(C1). Anti-AQP4 and anti-NMDAR were positive in CSF. Steroid-pulse therapy ameliorated her symptoms.A 37-year-old male experienced worsening vision. He was confirmed neurosyphilis since the CSF tests for syphilis were positive. Protein was elevated and the oligoclonal IgG bands(OB) and anti-NMDAR was positive in CSF. Anti-aquaporin 4(AQP4) antibodies and NMO-IgG were negative. Cranial MRI showed high FLAIR signal on frontal lobe and low T2 signal adjacent to the right cornu posterious ventriculi lateralis. Treatment for neurosyphlis was commenced with gradual improvement.A 39-year-old male, developed serious behavioral and psychiatric symptoms. Examination showed abnormal pupils and unsteady gait. He was confirmed neurosyphilis according to the CSF tests for syphilis. Anti-NMDAR was positive in CSF and serum. Cranial MRI showed lateral ventricles and the third ventricle enlargement and signal abnormality involving bilateral temporal lobe, corona radiate and centrum semiovale. PenicillinG, pulsed methylprednisolone and intravenous immunoglobulin was administered. He was stable.ConclusionAnti-NMDAR encephalitis can present in atypical types. When relapsing, it may present with partial aspects or with isolated symptoms of the full-blown syndrome. Anti-NMDAR encephalitis may be related to neuromyelitis optica spectrum disorder or neurosyphilis.
The spectrum of CKD is changing in China, with variations over time and geographic regions, which has implication regarding developing the prevention strategy of CKD. This article is protected by copyright. All rights reserved.
Objectives Sarcopenia and systemic inflammation can affect survival of advanced‐stage oral squamous cell carcinoma (OSCC) patients; however, their reciprocal associations with survival outcomes are yet to be investigated. Study Design Retrospective review at a tertiary cancer center. Methods Patients with stage III‐IVB OSCC that underwent surgery and (chemo)radiotherapy at our institution between 2010 and 2015 were reviewed. Skeletal muscle index (SMI) was assessed using computed tomography scans at the C3 vertebra. Sarcopenia was defined at the lowest sex‐specific tertile for SMI. Systemic inflammation was estimated using the modified Glasgow prognostic score (mGPS), which ranges from 0 to 2 based on serum C‐reactive protein and albumin levels. The predictors of overall survival (OS) were evaluated using Cox regression models. Results A total of 174 patients were included in the study. The cut‐off values for sarcopenia were set at SMI <52.4 cm2/m2 (men) and < 36.2 cm2/m2 (women) corresponding to the lowest sex‐specific tertile. An mGPS 1–2 was independently associated with sarcopenia (odds ratio: 2.05; 95% confidence interval: 1.06–3.97; P = .03). On multivariate analysis for OS, sarcopenia and mGPS 1–2 independently predicted OS (hazard ratio: 2.12; 95% confidence interval: 1.17–3.85; P = .01 and hazard ratio: 7.85; 95% confidence interval: 3.7–16.65; P < .001, respectively). Patients with both sarcopenia and mGPS 1–2 (vs. neither) had worse OS (hazard ratio: 16.80; 95% confidence interval: 6.01–46.99; P < .001). Conclusions Sarcopenia and systemic inflammation may exert a negative synergistic prognostic impact in advanced‐stage OSCC patients. Level of Evidence 4 Laryngoscope, 131:E1530–E1538, 2021
BackgroundEnterovirus 71 (EV71) is major cause of hand, foot and mouth disease. Large epidemics of EV71 infection have been recently reported in the Asian-Pacific region. Currently, no vaccine is available to prevent EV71 infection.ResultsThe peptide (VP4N20) consisting of the first 20 amino acids at the N-terminal of VP4 of EV71 genotype C4 were fused to hepatitis B core (HBcAg) protein. Expression of fusion proteins in E. coli resulted in the formation of chimeric virus-like particles (VLPs). Mice immunized with the chimeric VLPs elicited anti-VP4N20 antibody response. In vitro microneutralization experiments showed that anti-chimeric VLPs sera were able to neutralize not only EV71 of genotype C4 but also EV71 of genotype A. Neonatal mice model confirmed the neutralizing ability of anti-chimeric VLPs sera. Eiptope mapping led to the identification of a “core sequence” responsible for antibody recognition within the peptide.ConclusionsImmunization of chimeric VLPs is able to elicit antibodies displaying a broad neutralizing activity against different genotypes of EV71 in vitro. The “core sequence” of EV71-VP4 is highly conserved across EV71 genotypes. The chimeric VLPs have a great potential to be a novel vaccine candidate with a broad cross-protection against different EV71 genotypes.
SUMMARYWe have previously shown that tolerance can be induced against acute experimental autoimmune encephalomyelitis (EAE) in Lewis rats by bone marrow-derived dendritic cells (DC) that have been pulsed in vitro with encephalitogenic myelin basic protein peptide 68±86 (MBP 68±86), and injected subcutaneously into healthy rats prior to immunization with MBP 68±86 plus complete Freund's adjuvant. To elucidate better the properties of tolerogenic DC, we here compared plastic-adherent DC with¯oating, non-adherent DC, which were cultured for 7 days in the presence of granulocyte± macrophage colony-stimulating factor plus interleukin-4 (IL-4). Adherent DC expressed high levels of IL-10 mRNA and protein, and low levels of IL-12 mRNA and showed high expression of CD54 compared with¯oating DC. Proliferation, nitrite concentration and capacity for antigen presentation were lower in adherent DC than in¯oating DC. There were no differences between adherent and¯oating DC regarding expression of CD11c, OX62, major histocompatibility complex class II, CD80, or CD86. Most importantly, we observed that adherent DC induced tolerance to EAE in vivo when injected subcutaneously into Lewis rats prior to immunization, while¯oating DC did not. Adherent DC-mediated tolerance to EAE was associated with augmented proliferation, nitric oxide production and frequency of apoptotic cells as well as with up-regulation of transforming growth factor-b (TGF-b) -expressing cells in T-cell areas of lymph nodes. Tolerance induction by adherent DC seems to be related to a nitric oxide±apoptosis pathway and to upregulation of TGF-b-expressing cells.
Conventional methods that have been developed to immobilize the mouth and tongue for radiotherapy (RT) in head and neck cancer (HNC) treatment have been unsatisfactory. We, therefore, developed three-dimensional (3D), customizable, silicone bite blocks and examined their clinical feasibility. For HNC patients, before RT, the 3D printed bite blocks were fabricated based on primary computed tomography (CT) simulation images. The placement of the 3D bite blocks was followed by a secondary CT simulation before RT planning was finalized. Dosimetric parameters and positioning verification achieved with the propose bite blocks were compared with conventional universal oral corks. The 3D printed bite blocks were conformal to the occlusal surface, ensuring immobilization of the tongue without eliciting a gag reflex, and an elastic and firm texture that supports opening of the mouth, with a smooth surface with tolerable intraoral tactility. The dosimetry of patients using the proposed bite blocks showed better coverage of the planning target volume and surface of a tumour bed along with reduction in normal tissue doses. Good concordance of positioning by 3D printed bite blocks during the RT course was verified. The 3D printed bite blocks with silicone might be a customizable, safe, and practical advanced technology in RT for HNC.
BackgroundExperimental studies showed that 25-hydroxy-vitamin D [25(OH)D] deficiency (defined as 25-hydroxy-vitamin D < 15 ng/ml) has been associated with CKD progression. Patients with IgA nephropathy have an exceptionally high rate of severe 25(OH)D deficiency; however, it is not known whether this deficiency is a risk factor for progression of IgA nephropathy. We conducted this study to investigate the relationship between the plasma level of 25(OH)D and certain clinical parameters and renal histologic lesions in the patients with IgA nephropathy, and to evaluate whether the 25(OH)D level could be a good prognostic marker for IgA nephropathy progression.MethodsA total of 105 patients with biopsy-proven IgA nephropathy were enrolled between 2012 and 2015. The circulating concentration of 25(OH)D was determined using serum samples collected at the time of biopsy. The primary clinical endpoint was the decline of estimated glomerular filtration rate (eGFR; a 30 % or more decline compared to the baseline).ResultsMean eGFR decreased and proteinuria worsened proportionally as circulating 25(OH)D decreased (P < 0.05). The 25(OH)D deficiency was correlated with a higher tubulointerstitial score by the Oxford classification (P = 0.008). The risk for reaching the primary endpoint was significantly higher in the patients with a 25(OH)D deficiency compared to those with a higher level of 25(OH)D (P = 0.001). As evaluated using the Cox proportional hazards model, 25(OH)D deficiency was found to be an independent risk factor for renal progression [HR 5.99, 95 % confidence intervals (CIs) 1.59–22.54, P = 0.008].ConclusionA 25(OH)D deficiency at baseline is significantly correlated with poorer clinical outcomes and more sever renal pathological features, and low levels of 25(OH)D at baseline were strongly associated with increased risk of renal progression in IgAN.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-016-0378-4) contains supplementary material, which is available to authorized users.
Keywords: myocardial infarction, recurrent stroke, risk factors of stroke s u m m a r y Background: Recurrent stroke is often devastating, and can cause severe disability or death. Risk factors associated with recurrent strokes unrelated to atrial fibrillation have been well identified; however, it remains to be further elucidated whether the risk factors for recurrent stroke are the same in young as in older patients. Methods: Data from 1017 stroke patients unrelated to atrial fibrillation were retrospectively reviewed. Risk factors analyzed included sex, smoking history, previous history of ischemic stroke or transient ischemic attack, hypertension, diabetes mellitus, coronary atherosclerotic heart disease, and previous myocardial infarction. All patients were followed up via telephone 1 year after their initial strokes. Logistic regression was used to assess the associations between the various factors and risk of recurrent stroke events. Results: Predictive independent risk factors of recurrent stroke in older men included previous history of myocardial infarction [odds ratio (OR), 6.761; 95% confidence interval (CI), 1.030e44.371], ischemic stroke or transient ischemic attack (OR, 2.496; 95% CI, 1.567e3.976), diabetes mellitus (OR, 1.986; 95% CI, 1.223e3.227), and coronary atherosclerotic disease (OR, 1.733; 95% CI, 1.010e2.974). In young men, hypertension (OR, 1.709; 95% CI, 1.104e2.645), coronary atherosclerotic heart disease (OR, 1.812; 95% CI, 1.129e2.911), and previous history of ischemic stroke or transient ischemic attack (OR, 2.317; 95% CI, 1.580e3.397) were independent risk factors of recurrent strokes. Conclusion: The predictive independent risk factors of recurrent stroke differ between young and older stroke patients. Our findings may help guide the prevention of recurrent strokes.
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