Volume 100 ·  Issue 25 ·  2020

To explore the clinical features of post-viral-encephalitis autoimmune encephalitis (PVEAE).

Ten cases of PVEAE, who were hospitalized in the Neurology Department of Peking Union Medical College Hospital (PUMCH) between November 2014 and October 2019, were retrospectively reviewed. Clinical manifestation, immunology, neuroradiology, treatment and outcomes were analyzed.

There were 5 males and 5 females, with a median age of 44 (18, 66) years. Of 9 cases, the median interval between the two onsets of encephalitis was 37 (24, 60) days, and there was no obvious interval in case 7. In viral encephalitis phase, the peak modified Rankin scale (mRS) was 4.5 (4.0, 5.0) and the remission mRS was 2.0 (1.0, 3.0). In autoimmune encephalitis (AE) phase, the peak mRS was 4.0 (3.0, 5.0). Symptoms of AE included mental and behavioral abnormalities (10/10), amnesia (10/10), motor disorders (5/10), autonomic dysfunction (5/10), speech disorders (4/10), seizures (2/10) and consciousness disturbance (2/10). On average, each case presented with 4 (2, 6) symptoms. In AE phase, the positive rate of anti-N-methyl-D-aspartate (anti-NMDA) receptor antibody in cerebrospinal fluid (CSF) was 80% (8/10), while in serum it was only 20% (2/10). Neuroimaging showed that in AE phase, the lesions expanded in 8 cases, remained unchanged in 1 case and shrank in 1 case. In AE phase, 10 cases received first line treatments, and 2 cases accepted long-course immunotherapy. After treatment, symptoms of 9 cases were obviously relieved. The mRS for short-term and long-term outcomes was 2.0 (1.0, 4.0) and 1.0 (0, 2.0), respectively.

PVEAE might present with either typical biphasic course or monophasic/pseudo-monophasic course. In AE phase, anti-NMDA receptor antibody turned positive in most cases. Much importance should be attached to the recognition and diagnosis of PVEAE and treat it actively thereafter.

To study the clinical features, continuous care and prognosis of the patients with severe and refractory anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis after intensive care unit (ICU).

Clinical data of patients with severe and refractory anti-NMDAR encephalitis, who were transferred from ICU to general ward of neurology between December 2015 and October 2019, were retrospectively reviewed and analyzed in the study.

Twenty patients (11 females and 9 males) were enrolled in the study. The median course of disease when patients were transferred to general ward was 4.4 (2.0, 6.0) months. Six cases were alert, 6 cases were in a coma, 5 were in the early recovery phase and 3 were in the late recovery phase. Severe malnutrition, pneumonia, urinary tract infections, bedsores and leukocytopenia were common complications. Seven out of 18 patients were tested positive for cerebrospinal fluid anti-NMDAR antibodies with high titers (≥1∶100). During this continuous therapy stage,10 patients were treated with intravenous immunoglobulin (IVIg), 1 with methylprednisolone, 2 with rituximab, 1 with intrathecal methotrexate and 1 received intravenous cyclophosphamide. All Patients were prescribed a long-term immunotherapy (mycophenolate mofetil 1.5-3.0 g/d). Sixteen patients (80%) had good prognosis (modified Rankin Scale (mRS)≤2), and the mortality was 10%, with follow-up time of 17.0 (8.0, 27.0) months.

Patients with anti-NMDAR encephalitis, who are transferred from ICU, have severely impaired neurologic function. These patients need long-term individualized immunotherapy and continuous neurological care. Good outcomes can be achieved in most patients.

To investigated cognitive and cerebral blood flow changes in a cohort of patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis.

Fifteen patients with confirmed anti-NMDAR encephalitis from the First Affiliated Hospital of Anhui Medical University and the First Affiliated Hospital of University of Science and Technology of China between June 2015 and February 2019 were included in the study. Meanwhile, another 15 healthy subjects were selected as controls. All participants underwent neuropsychological tests for assessment of the clinical symptoms and arterial spin labeling (ASL) of magnetic resonance perfusion imaging scan were employed to evaluate cerebral perfusion. Then the relationship between changed cerebral blood perfusion and cognitive function was evaluated.

Patients with anti-NMDAR encephalitis showed significantly reduced overall cognitive function (Montreal cognitive assessment (MoCA)) than healthy controls (26.5±2.5 vs 28.6±1.9, P=0.015), they also exhibited poorer performance in immediate memory, recognition, attention, language and executive function than healthy controls (P<0.05). However, no significant differences in clinical symptoms, viability, mental state and mood were observed between the two groups (P>0.05). Patients with anti-NMDAR encephalitis showed significantly reduced total brain cerebral blood flow (CBF) compared with the healthy controls (0.949±0.028 vs 0.953±0.025, P=0.001). Compared with the healthy controls, the patients had decreased CBF in triangular and opercular parts of bilateral inferior frontal gyrus and left central frontal gyrus, however, they showed increased CBF in the left inferior temporal gyrus and left fusiform gyrus (all P<0.05). In NMDAR group, the CBF in left central anterior gyrus was negatively correlated with Stroop′s Color Word-word (r=-0.68, P=0.005). The CBF in left spindle gyrus was positively correlated with Stroop′s Color Word-word (r=0.62, P=0.015) and completion time of color trail test-A (r=0.81, P<0.001), respectively, however, it was negatively correlated with Chinese Auditory Verbal Learning Test-immediate (r=-0.59, P=0.020) and Verbal Fluency Test-animals (r=-0.58, P=0.024), respectively.

Patients with anti-NMDAR encephalitis have prevalent cognitive deficits such as memory, language, attention and executive dysfunction as well as changes in blood perfusion, which may be related to cognitive deficits. Changes in cerebral blood perfusion can be used as indicators for early diagnosis, disease monitoring and prognosis evaluation of anti-NMDAR encephalitis. Improving the cerebral blood flow of patients may promote the recovery of cognition.

To analyze the differences of clinical characteristics and outcomes between relapsing and monophasic patients with anti-leucine-rich glioma-inactivated 1 (anti-LGI1) encephalitis.

Medical records of confirmed anti-LGI1 encephalitic patients who underwent immunotherapy were retrospectively collected from January 2015 to January 2019 in the first affiliated hospital of Zhengzhou University. Clinical data, treatment methods, duration of treatment and outcomes were analyzed between the relapsing and monophasic groups.

Among the 33 anti-LGI1 encephalitic patients, there were 12 and 21 cases in the relapsing and monophasic groups, respectively. No difference was found in age, sex, precipitating factors, intensive care unit (ICU) admission, symptoms and modified Rankin Scale (mRS) score in the acute phase (P>0.05). As to the lab test and image examination, no statistic difference was found in serum and cerebral spinal fluid (CSF) positive rate, hyponatremia, abnormal rate of electrocardiogram (ECG), electroencephalogram (EEG), CSF and magnetic resonance imaging (MRI) and lesion locations (P>0.05). No difference was found in time to diagnose the disease between the 2 groups (P>0.05). The median immunotherapy period was 102.5 days in relapsing group and 194.0 days in monophasic group, with a statistic difference (P=0.001). No patients had bad outcomes in the monophasic group at the last follow-up, while 6 patients had poor outcomes in the relapsing group (4 patients died). The patients in relapsing group had a worse prognosis compared to those in the monophasic group (P=0.007).

Relapse is common in anti-LGI1 encephalitis. Patients in the relapsing group received a shorter term of immunotherapy and had worse outcomes than those in the monophasic group.

To describe the clinical features of anti-myelin oligodendrocyte glycoprotein (MOG) antibody-positive cortical encephalitis in children.

Patients who were hospitalized in Beijing Children′s Hospital from June 2018 to October 2019, with positive MOG antibodies and phenotype of cortical encephalitis were retrospectively analyzed. Cell-based assays (CBAs) were used to test MOG antibodies.

Five patients had the phenotype of cortical encephalitis during follow-up, with 3 females and 2 males. The age of onset ranged from 8 years to 12 years and 1 month. At the last follow-up, 3 cases exhibited a monophasic course and 2 cases were with relapse and remission courses. Six out of 8 episodes which had the phenotype of cortical encephalitis presented with seizures, among which 3 episodes had status epilepticus. None had recurrent seizures during remission. Other symptoms included fever (7/8), headache and vomiting (4/8), somnolence (3/8) and hemiplegia (1/8). Unilateral cortical swelling was observed in cerebral magnetic resonance imaging (MRI) of all patients, without any hemorrhage and necrosis. White blood cell (WBC) counts of cerebrospinal fluid increased, ranging from8×10⁶/L to 186×10⁶/L. All patients recovered well after treatment with intravenous immunogloblin and glucocorticoid. Two patients had relapses during follow-up and were additionally treated with mycophenolate mofetil.

Anti-MOG antibodies can induce cortical encephalitis. In clinical setting, fever, headache and seizures are common, however, severe consciousness disturbance and local neurological deficits are rare in these patients. Cerebral MRI shows unilateral cortical swelling without any hemorrhage and necrosis. Usually, immunotherapy works well. No patients exist repeated seizures in remission, but some patients may have relapses.

To explore the clinical efficacy of percutaneous endoscopic cervical discectomy (PECD) assisted by neurophysiology monitoring (NM) in the treatment of cervical spondylotic radiculopathy (CSR).

The clinical data of 55 patients with CSR treated in the Department of Spinal Surgery of Henan Provincial People′s Hospital from April 2015 to May 2018 were analyzed retrospectively. Among them, 29 patients were treated with multi-mode NM-assisted PECD (NM group) and 26 patients with PECD alone (PECD group). The gender, age, operation time, bleeding volume, average hospital stay and complications between the two groups were recorded and compared. In addition, the visual analogue score (VAS) of neck and upper limb pain and the score of Japanese Orthopedic Association (JOA) were compared between the two groups before operation, 1 month after the operation and at the last follow-up. These data between groups were compared by independent sample t test.

All patients in both groups were followed-up for at least 18 months. Neck VAS and upper limb VAS scores of two groups at 1 month post operation (neck: 2.1±1.2, 2.0±1.1; upper lamb: 2.4±1.2, 2.2±0.8) and the last follow-up (neck:0.8±0.5, 0.7±0.5; upper lamb: 0.8±0.7, 0.8±0.5) decreased significantly when compared with those before the operation (neck: 6.0±1.0, 5.9±1.0; upper lamb: 7.1±0.9, 7.4±0.9) (t=12.670-27.305, all P<0.05). However, there was no significant difference between the two groups (t=-1.107-0.917, all P>0.05). JOA scores of two groups at 1 month after the operation (12.7±0.8, 12.6±0.8), and at the last follow-up (14.6±0.7, 14.4±0.8) were all improved significantly from those before the operation (11.1±1.0, 10.9±0.8) (t=-11.074, -14.829, -9.603, -13.086, all P<0.05); however, there was no significant difference between the two groups (t=0.842, 0.003, both P>0.05). There was also no significant difference in bleeding volume, and operation time between the two groups, (t=-0.615, -0.922, P>0.05) but the average hospital stay and incidence of complications in the NM group were significantly lower than those in the PECD group (t=-2.815, χ ²=4.755, both P<0.05).

Multimode NM-assisted PECD in the treatment of CSR achieves satisfactory results, reducing the average hospital stay, reducing complications and improving surgical safety.

To identify predictors of massive blood loss after posterior hemivertebra resection for patients with congenital scoliosis.

The data of 106 children with congenital scoliosis were collected from June 2017 to June 2019 in Beijing Children′s Hospital. All the cases received posterior hemivertebra resection and internal fixation. The blood volume was estimated by weight and height. The visible blood loss was recorded according to medical record, and the hidden blood loss was calculated by OSTHEO formula. Perioperative information including age, gender, height, weight, Cobb and kyphosis angle, level fused, number of screws, operative time, and laboratory examinations was collected. Then multivariable linear regression was performed to determine the independent risk factors of blood loss.

All the surgeries were completed successfully. The mean age of the children was (7.3±2.3) years and the operative time was (162±56) min. The mean fused levels were 3 and the correction rate for deformity was 78.4%. The amount of blood loss was (568±208) ml which accounted for 42.3% of total blood volume. The visible and hidden blood loss was (334±193) ml and (234±199) ml, respectively, and which accounted for 58.8% and 41.2% of total blood loss. Multivariable linear regression analysis indicated that age, preoperative Cobb angle, the time of surgery and the number of fused levels were independent risk factors of total blood loss. Preoperative Cobb angle ≥40°, spinal fusion ≥4 levels and operative duration ≥140 min indicated more blood loss (all P<0.05).

The perioperative blood loss of congenital scoliosis is massive with a high percentage of hidden blood loss. The patients with severe deformity, more fused levels and increased operative time brings higher risk of massive blood loss.

To explore the correlation between quadriceps thickness (thickness of rectus femoris and vastus intermedius), cross-sectional area (cross-sectional area of the rectus femoris) and the strength score of the Medical Research Council (MRC) in critically ill patients, and to explore the changes in the length of hospital stay in the intensive care unit (ICU), and to determine the diagnostic value of muscle changes in the ICU-acquired weakness (ICU-AW).

Patients admitted to the Department of Critical Care Medicine from March to October in 2019 who were expected to stay for more than five days were enrolled in this study. The cross-sectional area of the rectus femoris, the thickness of the rectus femoris, the thickness of the vastus intermedius on the first day of the ICU (D₁), day 3 (D₃), and day 5 (D₅), day 7 (D₇), out of ICU (D_ICU), and the MRC muscle strength scores on the day of out of ICU prospectively were collected in all the patients, and the correlation and the regularity of quadriceps changes were analyzed. MRC>48 points on the day of dismiss of ICU were used as the standard for the diagnosis of ICU-AW, and the relationship between muscle changes of the quadriceps and ICU-AW was analyzed. Thet test or the Mann-Whitney U test was used for data analysis.

A total of 45 patients were included, including 25 males and 20 females, aged (58±10) years. The rectus femoris cross-sectional area, rectus femoris thickness, and vastus intermedius thickness decreased with the length of ICU hospital stay. The cross-sectional area, thickness of the rectus femoris muscle, and the vastus intermedius thickness were positively correlated with the MRC score (r=0.452, 0.411, 0.402, all P<0.05), and the changes were all negatively correlated with the MRC score (r=-0.682, -0.740, -0.734, all P<0.05). On the 3rd day after ICU admission, the best cutoff value of rectus muscle cross-sectional area atrophy rate for discrimination of ICU-AW was 6.0%, with a sensitivity of 66.7% and a specificity of 77.8%; on the 5th day, the best cutoff value of rectus femoris thickness atrophy rate was 14.5%, with a sensitivity of 77.8% and a specificity of 66.7%; on the 7th day, the best cutoff value of vastus intermedius thickness atrophy rate was 19.9%, with a sensitivity of 70.6% and a specificity of 87.5%.

Bedside ultrasound measurement of the quadriceps femoris cross-sectional area and thickness has certain diagnostic value for ICU-AW, and can identify patients with ICU-AW early.

To discuss the application value of the simultaneous determination of methotrexate (MTX) and 7-hydroxymethotrexate (7-OHMTX) in the delayed elimination of MTX for pediatric acute lymphoblastic leukemia (ALL).

Cross sectional study. A total of 97 children who received 192 high-dose MTX treatments cycles in Lu Daopei Hospital from April to August 2019 were enrolled. The peripheral blood was collected at 0,24,48 h after the end of MTX infusion and analyzed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). One hundred and ninety-two MTX treatments were divided into a normal MTX elimination group (n=149) and delayed elimination group (n=43) according to the standard of delayed elimination and divided into 0-9 year old group (n=95), 10-14 group (n=50), 15-18 group (n=47) according to age. The comparisons of the C_MTX, C_7-OHMTX between normal and delayed group was conducted as well as among different age groups. Receiver operator characteristic curve (ROC) of C_MTX-0h and C_7-OHMTX-0h was analyzed and the concentration corresponding to the maximum of the Youden index on the ROC was set as the warning value for delayed elimination. Correlation between the delayed elimination after the end of MTX infusion and toxicity was investigated and the percentage of delayed elimination was also analyzed.

The concentrations of MTX and 7-OHMTX were significantly higher in the delayed elimination group than the normal group. Immediately after infusion (0 h), a C_7-OHMTX-0h of >17.8 μmol/L (sensitivity 97.7%, specificity 54.4%) and a C _MTX-0h of >148.8 μmol/L (sensitivity 72.1%, specificity 84.6%) were found to be warning predictors of delayed elimination under the MTX treatment protocol. MTX delayed elimination was positively correlated with methotrexate-induced toxicities ( r=0.58, P<0.01). The percentage of hepatotoxicity and nephrotoxicity was 32.6% and 37.2% in the delayed elimination group, which was significantly higher than normal group of 12.8% and 3.4% (P<0.05). No significant difference was found in other toxicities. There was significant difference in C_MTX among different age groups but no significant difference in C_7-OHMTX.

Simultaneously determination of MTX and 7-OHMTX in plasma by HPLC-MS/MS in childhood ALL patients can provide a reference for clinical individualized medicine and pharmacokinetic research.

To investigate the effect of induction on maternal and neonatal outcomes of vaginal birth after cesarean section (VBAC).

Retrospective cohort study. A total of 452 pregnant women who underwent trail of labor after cesarean section (TOLAC) from January 2015 to March 2019 of Beijing Obstetrics and Gynecology Hospital, Capital Medical University were enrolled. According to the mode of the onset of labor, those 331 women who underwent VBAC were divided into spontaneous labor group (n=280) and induction group(n=51). According to induction methods, the pregnant women in the induction group was divided into the low-dose oxytocin subgroup (n=35) and other method subgroup (n=16, 9 cases with cervical ripening by balloon and 7 cases combined with oxytocin). The effect of induction on labor duration and maternal and neonatal outcome in VBAC were analyzed.

No maternal and neonatal death occurred. There were 23.0% (76/331) with forceps, 15.1% (50/331) of postpartum hemorrhage, and 24.5% (81/331) of fetal distress. The gravidity, birth weight and the gestational weeks of delivery in the induction group were significantly higher than those in the spontaneous onset group [2.0 (2.0-3.0) vs 2.0(1.0-2.0) times, 39.0(38.0-40.0) vs 38.0(37.0-39.0) weeks, (3 467±372) vs (3 168±538) g, Z=-3.548,-3.892,-3.813, all P<0.01]. The duration of the second stage of labor was significantly longer than that of the spontaneous onset group [43(26-60) vs 30(17-49) min, Z=-2.145,P<0.05], but the duration of the first stage, the total duration of labor, the rate of forceps, the incidence of postpartum hemorrhage, the rate of perineal incision and the incidence of fetal distress were not obvious different (all P>0.05). The duration of the first stage and total duration in oxytocin group were significantly shorter than those other method group [260(210-435) vs 325(250-490) min, 450(355-620) vs 523(370-668) min, Z=-2.001,-1.913, all P<0.05]. There were not significantly different in the duration of second stage, mode of delivery, perineal injury, the rate of postpartum hemorrhage, and fetal distress in the two groups (all P>0.05).

Pregnant women who have undergone TOLAC after caesarean section can be induced after fully evaluation. Although induction prolongs the labor duration, it does not affect the maternal and neonatal complication rate.

To investigate the characteristics of comorbidities and polypharmacy in middle-aged and elderly patients and assess the potential risk of drug-drug interactions.

Retrospective analysis was carried out among the outpatients aged ≥45 years in the Second Medical Center of the PLA General Hospital from January to December 2016. The patient′s comorbidities and polypharmacy were collected from the electronic medical records and annual physical examination reports. The frequency and grade of drug-drug interactions (DDIs) were summarized and ranked by Lexicomp^® Drug Interactions database.

A total of 1 340 patients were enrolled in the study, of which 930 patients (69.40%) used 5 or more drugs, and 660 patients (49.25%) used 10 or more drugs. Multivariate analysis showed that age and the number of comorbidities were independent factors of excessive polypharmacy. The total frequency of detecting clinically significant DDIs (C+D+X) was 857 cases, with 0.8 cases per person by Lexicomp^® Drug Interactions database. Among them, medications for nervous system accounted for the highest proportion of X-level DDIs.

The comorbidities and polypharmacy in middle-aged and elderly patients are very prominent. More attention should be paid to drug interactions, especially in patients with neurological medication.

To explore the possible mechanisms of simvastatin-induced apoptosis in lung adenocarcinoma cells.

The experiment was divided into control group (vehicle treated A549 cells), different concentrations (10, 20, 40, 80 mg/L) simvastatin group (simvastatin treated with different concentrations of A549 cells), aspartate specific proteinase (caspase) inhibitor (Z-VAD-FMK) group (50 μmol/L Z-VAD-FMK treated A549 cells), 40 mg/L simvastatin combined with Z-VAD-FMK group (40 mg/L simvastatin combined with 50 μmol/L Z-VAD-FMK co-treated A549 cells), interleukin-6 (IL-6) group (IL-6 acts on A549 cells) and different concentrations (10, 20, 40 mg/L) simvastatin combined with IL-6 group (simvastatin combined with IL-6 act on A549 cells). Cell counting kit-8 (CCK8) method was used to detect the effect on survival rate of lung adenocarcinoma A549 cells; Flow cytometry was used to detect the effect of simvastatin on A549 cell cycle; Mitochondrial membrane potential-1 (JC-1) fluorescent probe was wsed to detect the effect of simvastatin on mitochondrial membrane potential (MMP); Flow-type phosphatidl serine protein antibody Annexin V/propidium iodide (Annexin V-FITC/PI) double staining method was used to detect the effect of simvastatin on A549 cell apoptosis; CCK8 method was used to detect the effect of Z-VAD-FMK on the survival rate of A549 cells; TdT-mediated 2′-deoxyuridine 5′-triphosphate (dUTP) nick end labeling (TUNEL) method was used to detect the effect of Z-VAD-FMK on simvastatin-induced apoptosis in A549 cells; Western blot method was used to detect the effect of simvastatin on the expression levels of Janus kinase 2 and activation of signal transducers and activators of transcription 3 (JAK2/STAT3) pathway-related proteins phosphorylated JAK2 (p-JAK2), JAK2, phosphorylated STAT3 (p-STAT3), and STAT3 before and after the activator IL-6 of JAK2/STAT3 pathway acted on A549 cells.

The survival rates of A549 cells in the 20-80 mg/L simvastatin-treated groups were significantly lower than that in the control group (all P<0.05), and gradually decreased with the increase of the concentration of the simvastatin and the extension of the action time. The cells in the G₀/G₁ phase of the simvastatin group were significantly higher than those in the control group, and the cells in the G₂/M phase were significantly lower than those in the control group (all P<0.01). The MMP of the treatment group with different concentrations of simvastatin was significantly lower than that of the control group (all P<0.05). The apoptosis rate of the 20 mg/L and 40 mg/L simvastatin-treated group was significantly higher than that of the control group (both P<0.01). The cell survival rate of the 40 mg/L simvastatin group and the 40 mg/L simvastatin combined with Z-VAD-FMK group were (52.2±2.7)% and (57.5±3.8)%, respectively, were lower than that of the control group (100.0±2.7)% (both P<0.01). But the difference between 40 mg/L simvastatin group and the simvastatin combined with Z-VAD-FMK group was not statistically significant (P>0.05). The cell numbers with positive fluorescent staining in the 40 mg/L simvastatin group were significantly more than those in the control group, but the cell numbers with positive fluorescent staining in the 40 mg/L simvastatin combined with Z-VAD-FMK group had no statistical significance compared with the simvastatin group (P>0.05). The specific value of p-JAK2/JAK2 and p-STAT3/STAT3 protein relative expressions in the simvastatin-treated group (20, 40 mg/L) were significantly lower than that in the control group, respectively (both P<0.05). The specific value of p-JAK2/JAK2 and p-STAT3/STAT3 protein relative expressions in IL-6 group were significantly higher than those in control group (both P<0.05), the specific value of p-JAK2/JAK2 and p-STAT3/STAT3 protein relative expressions in simvastatin (20, 40 mg/L) combined with IL-6 groups were lower than those in IL-6 group (all P<0.05), respectively.

Simvastatin can induce the apoptosis of A549 cells through a non-caspase-dependent mitochondrial apoptosis pathway, which may be achieved by inhibiting the JAK2/STAT3 pathway.