Upadacitinib for refractory ulcerative colitis with primary nonresponse to infliximab and vedolizumab: A case report.

BACKGROUND: Many patients with ulcerative colitis (UC) do not respond well to, or tolerate conventional and biological therapies. There is currently no consensus on the treatment of refractory UC. Studies have demonstrated that the selective Janus kinase 1 inhibitor upadacitinib, a small-molecule drug, is effective and safe for treating UC. However, no studies have revealed that upadacitinib is effective in treating refractory UC with primary nonresponse to infliximab and vedolizumab. CASE SUMMARY: We report the case of a 44-year-old male patient with a chief complaint of bloody diarrhoea with mucus and pus, in addition to dizziness. The patient had recurrent disease after receiving mesalazine, prednisone, azathioprine, infliximab and vedolizumab over four years. Based on the endoscopic findings and pathological biopsy, the patient was diagnosed with refractory UC. In particular, the patient showed primary nonresponse to infliximab and vedolizumab. Based on the patient's history and recurrent disease, we decided to administer upadacitinib. During hospitalisation, the patient was received upadacitinib under our guidance. Eight weeks after the initiation of upadacitinib treatment, the patient's symptoms and endoscopic findings improved significantly. No notable adverse reactions have been reported to date. CONCLUSION: Our case report suggests that upadacitinib may represent a valuable strategy for treating refractory UC with primary nonresponse.

[Disease Characteristics, Treatment, and Prognosis of Chinese Patients with Autoimmune Encephalitis: A Retrospective Study].

OBJECTIVE: To investigate the clinical features and prognosis of autoimmune encephalitis (AE). METHODS: Accessing data from the electronic medical records of patients receiving care at West China Hospital, Sichuan University, China between 2013 and 2019, we conducted a retrospective study of the disease characteristics, laboratory examinations, treatment, and prognosis of AE patients. Before they were discharged, modified Rankin Scale (mRS) was used to assess the prognosis of AE patients and their mRS scores were then used to categorize patients as having good prognosis (mRS scores of 0-2) or poor prognosis (mRS scores of 3-6). Multivariate logistic regression was used to analyze risk factors associated with poor prognosis. RESULTS: A total of 121 patients were included in the study. The male-to-female ratio was 1∶1.1. At the time of diagnosis, patients were mainly from the age group of young to middle-aged individuals. Among the 121 patients, 64.5% (78 patients) had anti-N-methyl D-aspartate receptor (NMDAR) encephalitis, accounting for the largest proportion. 33.1% (40 patients) first visited the Department of Psychiatry for medical assistance. 62.8% (76 patients ) showed prodromal symptoms. The common clinical manifestations of the AE patients at the time of admission included cognitive dysfunction (104 patients, 86.0%), thought disorder (90 patients, 74.4%), and altered behaviors (88 patients, 72.7%). The NMDAR antibody titers were higher in the cerebrospinal fluid (CSF) than those in the serum. Double-positive antibodies were detected in 6 patients. No abnormality was observed in the brain magnetic resonance imaging (MRI) of 42 patients (34.7%) . Electroencephalography abnormalities were observed in 71 patients (58.7%). 111 patients (91.7%) received first-line immunotherapy and 61 patients (50.4%) still had neuropsychiatric deficits when they were discharged. Multivariate logistic regression revealed that consciousness disorder (odds ratio [ OR] =4.230, 95% confidence interval [ CI] : 1.540-11.617; P=0.005), altered behavior ( OR=2.997, 95% CI: 1.068-8.406; P=0.037) and movement disorder ( OR=7.753, 95% CI: 1.446-41.578; P=0.017) were risk factors for poor clinical prognosis of AE patients. CONCLUSIONS: Patients with AE mainly manifest cognitive damage. Half of the patients left neuropsychiatric deficits. The relationship between CSF titers and serum titers is unparalleled. The options of immunotherapy show no difference in their influence on prognosis. Cognitive dysfunction, altered behavior and movement disorder are independent risk factors for a poor prognosis at discharge.

Quantitative analysis of retinal vasculature in normal eyes using ultra-widefield fluorescein angiography.

AIM: To quantify the area and density of retinal vascularity by ultra-widefield fluorescein angiography (UWFA). METHODS: In a retrospective study, UWFA images were obtained using an ultra-widefield imaging device in 42 normal eyes of 42 patients. Central and peripheral steered images were used to define the edge of retinal vasculature by a certified grader. The length from the center of the optic disc to the edge of retinal vascularity (RVL) in each quadrant and the total retinal vascular perfusion area (RVPA) were determined by the grader using OptosAdvance software. The density of retinal vascularity (RVD) was quantified in different zones of central-steered images using Image J software. RESULTS: Among 42 healthy eyes, the values for mean RVL in each quadrant were 19.007±0.781 mm (superior), 18.467±0.869 mm (inferior), 17.738±0.622 mm (nasal) and 24.241±1.336 mm (temporal). The mean RVPA was 1140.117±73.825 mm2. The mean RVD of the total retina was 4.850%±0.638%. RVD varied significantly between different retina zones (P<0.001), and significant differences existed in the RVD values for total retinal area in patients over 50 years old compared to those under 50 years old (P=0.033). No gender difference was found. CONCLUSION: The UWFA device can be a promising tool for analyzing the overall retinal vasculature and may provide a better understanding of retinal vascular morphology in normal eyes. Aging may be related to lower RVD.

Case Report: Neuronal Intranuclear Inclusion Disease With Oromandibular Dystonia Onset.

Background: Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease. Because of variable clinical manifestations, NIID was often misdiagnosed. According to published case reports, the common clinical manifestations of NIID include dementia, muscle weakness, autonomic impairment, sensory disturbance, rigidity, ataxia convulsions, etc. However, no cases of oromandibular dystonia were mentioned. Case Presentation: We describe a case of a 58-year-old woman presenting with mouth involuntary chewing initially. She started to show hand tremors, ataxia, and walking instability until 2 years later. Diffusion-weighted imaging showed high intensity signal along the corticomedullary junction. Fluid-attenuated inversion recovery imaging showed white matter hyperintensity. Electromyography (EMG) indicated peripheral nerve degeneration. Neuropsychological testing showed memory loss. Finally, skin biopsy and GGC repeat expansions in the NOTCH2NLC (Notch 2 N-terminal like C) gene confirmed the diagnosis of NIID. Conclusion: This case demonstrated that oromandibular dystonia could be the first symptom of NIID. This case report provides new characteristics of NIID and broadens its clinical spectrum.

A radiomics signature to identify malignant and benign liver tumors on plain CT images.

BACKGROUND: In regular examinations, it may be difficult to visually identify benign and malignant liver tumors based on plain computed tomography (CT) images. RCAD (radiomics-based computer-aided diagnosis) has proven to be helpful and provide interpretability in clinical use. OBJECTIVE: This work aims to develop a CT-based radiomics signature and investigate its correlation with malignant/benign liver tumors. METHODS: We retrospectively analyzed 168 patients of hepatocellular carcinoma (malignant) and 117 patients of hepatic hemangioma (benign). Texture features were extracted from plain CT images and used as candidate features. A radiomics signature was developed from the candidate features. We performed logistic regression analysis and used a multiple-regression coefficient (termed as R) to assess the correlation between the developed radiomics signature and malignant/benign liver tumors. Finally, we built a logistic regression model to classify benign and malignant liver tumors. RESULTS: Thirteen features were chosen from 1223 candidate features to constitute the radiomics signature. The logistic regression analysis achieved an R = 0.6745, which was much larger than Rα = 0.3703 (the critical value of R at significant level α = 0.001). The logistic regression model achieved an average AUC of 0.87. CONCLUSIONS: The developed radiomics signature was statistically significantly correlated with malignant/benign liver tumors (p < 0.001). It has potential to help enhance physicians' diagnostic abilities and play an important role in RCADs.

Clinicopathologic characterization and abnormal autophagy of CSF1R-related leukoencephalopathy.

BACKGROUND: CSF1R-related leukoencephalopathy, also known as hereditary diffuse leukoencephalopathy with spheroids (HDLS), is a rare white-matter encephalopathy characterized by motor and neuropsychiatric symptoms due to colony-stimulating factor 1 receptor (CSF1R) gene mutation. Few of CSF1R mutations have been functionally testified and the pathogenesis remains unknown. METHODS: In order to investigate clinical and pathological characteristics of patients with CSF1R-related leukoencephalopathy and explore the potential impact of CSF1R mutations, we analyzed clinical manifestations of 15 patients from 10 unrelated families and performed brain biopsy in 2 cases. Next generation sequencing was conducted for 10 probands to confirm the diagnosis. Sanger sequencing, segregation analysis and phenotypic reevaluation were utilized to substantiate findings. Functional examination of identified mutations was further explored. RESULTS: Clinical and neuroimaging characteristics were summarized. The average age at onset was 35.9 ± 6.4 years (range 24-46 years old). Younger age of onset was observed in female than male (34.2 vs. 39.2 years). The most common initial symptoms were speech dysfunction, cognitive decline and parkinsonian symptoms. One patient also had marked peripheral neuropathy. Brain biopsy of two cases showed typical pathological changes, including myelin loss, axonal spheroids, phosphorylated neurofilament and activated macrophages. Electron microscopy disclosed increased mitochondrial vacuolation and disorganized neurofilaments in ballooned axons. A total of 7 pathogenic variants (4 novel, 3 documented) were identified with autophosphorylation deficiency, among which c.2342C > T remained partial function of autophosphorylation. Western blotting disclosed the significantly lower level of c.2026C > T (p.R676*) than wild type. The level of microtubule associated protein 1 light chain 3-II (LC3-II), a classical marker of autophagy, was significantly lower in mutants expressed cells than wild type group by western blotting and immunofluorescence staining. CONCLUSIONS: Our findings support the loss-of-function and haploinsufficiency hypothesis in pathogenesis. Autophagy abnormality may play a role in the disease. Repairing or promoting the phosphorylation level of mutant CSF1R may shed light on therapeutic targets in the future. However, whether peripheral polyneuropathy potentially belongs to CSF1R-related spectrum deserves further study with longer follow-up and more patients enrolled. TRIAL REGISTRATION: ChiCTR, ChiCTR1800015295. Registered 21 March 2018.

[The clinical and pathological features of rhinocerebral mucormycosis].

OBJECTIVE: To investigate the clinical and pathological features of rhinocerebral mucormycosis. METHODS: The clinical data of three cases of mucormycosis were collected and analyzed. Pathological examination was conducted by autopsy or biopsy. RESULTS: All the three cases of mucormycosis had diabetic ketoacidosis. The early symptoms were fever, periocular and temporal headache. Gradually, orbital apex syndrome, periocular skin cellulitis and necrosis developed. Examination of nose revealed black necrotic turbinates. Meningeal signs and hemiplegia may also occur. Frontal hemorrhagic infarction was seen in pathology. A large amount of mucor fungi were found in the mucosa of nasal sinuses necrotic brain tissue under microscope. CONCLUSIONS: Rhinocerebral mucormycosis is a rare complication which was mainly seen in patients with diabetic ketoacidosis. The lesion invaded nose, eyes and brain with a high mortality.

[Phrenic radix conduction time in inflammatory demyelinating polyneuropathy patients].

OBJECTIVE: To investigate the features and application of phrenic radix conduction time (PRCT) in inflammatory demyelinating polyneuropathy (IDP) patients. METHODS: Distal motor latency (DML) was recorded by stimulating phrenic nerve electrically and phrenic nerve root magnetically in 20 IDP patients with surface electrodes at intercostal space. The difference of the two DML was calculated and compared with those recorded previously from 61 sides in 31 healthy control subjects. RESULTS: PRCT of the IDP patients was longer than that of the controls, and it correlated with the severity of clinical dyspnea. The abnormal rate of PRCT was higher than the incidence of clinical dyspnea. CONCLUSIONS: PRCT could reflect the functional status of the spinal roots related to respiration in IDP patients at an electrophysiological level. It correlates well with the degree of clinical dyspnea. Its detection is helpful to find out the subclinical dyspnea in IDP patients.