Clinical features of NOTCH2NLC-related neuronal intranuclear inclusion disease.

BACKGROUND: Abnormal expanded GGC repeats within the NOTCH2HLC gene has been confirmed as the genetic mechanism for most Asian patients with neuronal intranuclear inclusion disease (NIID). This cross-sectional observational study aimed to characterise the clinical features of NOTCH2NLC-related NIID in China. METHODS: Patients with NOTCH2NLC-related NIID underwent an evaluation of clinical symptoms, a neuropsychological assessment, electrophysiological examination, MRI and skin biopsy. RESULTS: In the 247 patients with NOTCH2NLC-related NIID, 149 cases were sporadic, while 98 had a positive family history. The most common manifestations were paroxysmal symptoms (66.8%), autonomic dysfunction (64.0%), movement disorders (50.2%), cognitive impairment (49.4%) and muscle weakness (30.8%). Based on the initial presentation and main symptomology, NIID was divided into four subgroups: dementia dominant (n=94), movement disorder dominant (n=63), paroxysmal symptom dominant (n=61) and muscle weakness dominant (n=29). Clinical (42.7%) and subclinical (49.1%) peripheral neuropathies were common in all types. Typical diffusion-weighted imaging subcortical lace signs were more frequent in patients with dementia (93.9%) and paroxysmal symptoms types (94.9%) than in those with muscle weakness (50.0%) and movement disorders types (86.4%). GGC repeat sizes were negatively correlated with age of onset (r=-0.196, p<0.05), and in the muscle weakness-dominant type (median 155.00), the number of repeats was much higher than in the other three groups (p<0.05). In NIID pedigrees, significant genetic anticipation was observed (p<0.05) without repeat instability (p=0.454) during transmission. CONCLUSIONS: NIID is not rare; however, it is usually misdiagnosed as other diseases. Our results help to extend the known clinical spectrum of NOTCH2NLC-related NIID.

Diagnosis of Enterococcus faecalis meningitis associated with long-term cerebrospinal fluid rhinorrhoea using metagenomics next-generation sequencing: a case report.

BACKGROUND: Enterococcus faecalis (E. faecalis) meningitis is a rare disease, and most of its occurrences are of post-operative origin. Its rapid diagnosis is critical for effective clinical management. Currently, the diagnosis is focused on cerebrospinal fluid (CSF) culture, but this is quite limited. By comparison, metagenomic next-generation sequencing (mNGS) can overcome the deficiencies of conventional diagnostic approaches. To our knowledge, mNGS analysis of the CSF in the diagnosis of E. faecalis meningitis has been not reported. CASE PRESENTATION: We report the case of E. faecalis meningitis in a 70-year-old female patient without a preceding history of head injury or surgery, but with an occult sphenoid sinus bone defect. Enterococcus faecalis meningitis was diagnosed using mNGS of CSF, and she recovered satisfactorily following treatment with appropriate antibiotics and surgical repair of the skull bone defect. CONCLUSIONS: Non-post-traumatic or post-surgical E. faecalis meningitis can occur in the presence of occult defects in the cranium, and mNGS technology could be helpful in diagnosis in the absence of a positive CSF culture.

Idiopathic thrombocytopenic purpura with brain abscess caused by Nocardia farcinica diagnosed using metagenomics next-generation sequencing of the cerebrospinal fluid: a case report.

BACKGROUND: Brain abscesses caused by Nocardia farcinica are rare, and mostly occur in immunocompromised individuals. Rapid and accurate diagnosis of nocardiosis is challenging. Due to the inadequate performance of conventional diagnostic methods for Nocardia infection, metagenomics next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) has the potential to improve the diagnosis intracranial nocardiosis. CASE PRESENTATION: We report a case of 50-year-old man with brain abscess caused by Nocardia farcinica. The patient had a idiopathic thrombocytopenic purpura complication that required long-term methylprednisolone administration. His chest image showed multiple lesions, which had been misdiagnosed as lung cancer, and his head image showed multiple intracranial metastases. No pathogen was detected in routine examinations including blood culture, sputum culture and traditional culture methods of cerebrospinal fluid. In order to accurately identify the pathogen, mNGS was used to detect Nocardia in CSF. Although the patient's condition improved after using sensitive antibiotics, he transferred to the local hospital for treatment because of many complicated diseases and family financial limitations. CONCLUSION: This case highlights the value of mNGS in the diagnosis of Nocardia brain abscess, and emphasizes the inadequate sensitivity of conventional diagnostic methods for Nocardia infection. Using mNGS can facilitate early and accurate detection of Norcadia-associated of meningitis in immunocompromised patients, thereby reducing unnecessary use of antibiotics and reducing mortality of the disease.

A sample model established by S-index predicting overall survival after curative resection of primary hepatocellular carcinoma.

PURPOSE: Prognostic prediction after curative resection of primary hepatocellular carcinoma (PHCC) remains an arduous task. The S-index calculated from γ-glutamyl transpeptidase, albumin, and platelets is reported to predict the severity of liver fibrosis. We constructed a nomogram for predicting the survival probability of PHCC based on a new indicator, the S-index, combined with other routine clinical parameters. PATIENTS AND METHODS: We selected 490 patients with PHCC postradical surgery at the First Affiliated Hospital of Wenzhou Medical University between January 2007 and January 2014. The subjects were randomly allocated into the training cohort and the validation cohort in the ratio 7:3 by the digital method. Important variables screened by univariate analysis were included in multivariate analysis to obtain independent risk factors for predicting the prognosis of PHCC. The construction of the nomogram was based on Cox proportional hazard regression models. The concordance index (C-index) was used in the nomogram for evaluating the model performance for prognosis. We drew time-dependent receiver operating characteristic curves to compare our model with other staging systems. RESULTS: The nomogram based on six independent risk factors after multivariate analyses had good predictive power after radical surgery of PHCC. In the training and validation groups, the C-index of the nomogram was highly consistent for evaluating survival from PHCC. Compared with the traditional scoring system, the areas under time-dependent receiver operating characteristic curves were 0.7382, 0.7293, and 0.7520 for 1-, 3-, and 5-year overall survival, respectively. In summary, the nomogram showed excellent results in terms of prognosis of PHCC. CONCLUSION: Based on the S-index and the other clinical indicators, we developed a precise nomogram that predicts the survival probability of patients with PHCC after radical surgery. This tool can provide effective information for surgeons and patients.

Expression of microRNA 638 and sex-determining region Y-box 2 in hepatocellular carcinoma: Association between clinicopathological features and prognosis.

The aim of the present study was to determine the expression profile of microRNA 638 (miR-638) and sex-determining region Y-box 2 (SOX2) in hepatocellular carcinoma (HCC), and to investigate their association with clinicopathological features and survival. Reverse transcription-quantitative polymerase chain reaction analysis was used to investigate miR-638 and SOX2 expression in 78 patients with HCC. Western blot and immunohistochemical analyses were performed in order to determine SOX2 protein expression in HCC samples. Combined with the clinical postoperative follow-up data, the expression of miR-638 and SOX2 and the association between this and the prognostic values of patients with HCC were statistically analyzed. The results of the present study confirmed that miR-638 expression in tumor tissues was significantly downregulated (P<0.001), while SOX2 expression was significantly increased, compared with healthy control tissues (P<0.05). In addition, a significant inverse correlation between miR-638 and SOX2 expression was also observed in the HCC tissues (r=-0.675; P<0.05). Clinicopathological correlation analysis demonstrated that reduced miR-638 and elevated SOX2 expression was significantly associated with the Tumor-Node-Metastasis stage and portal vascular invasion (P<0.05). However, no significant differences were observed in other clinicopathological features, including age, sex, tumor size, tumor differentiation and hepatitis status (P>0.05). Notably, follow-up analysis revealed that patients with HCC with low miR-638 expression and high SOX2 expression tended to have a significantly shorter postoperative survival time (P<0.001). It was concluded that miR-638 may serve a vital role in the occurrence and progression of HCC by regulating SOX2 expression and thus, that miR-638 and SOX2 may be critical as novel diagnostic and prognostic biomarkers for HCC.