Volume 101 ·  Issue 31 ·  2021

Refractory myasthenia gravis is an intractable state during treatment. The common causes of refractory treatment in most patients include: overwork, malnutrition, infections, insomnia, cognitive and emotional disorders, and so on. Only targeting the poor curative effect from the surface of the intractable state caused indecisive decisions and is difficult to win a success. Therefore, identifying "refractory state" can not only see the essence through the phenomenon, but also apply the right medicine, thereby killing two birds with one stone.

Accelerated rehabilitation surgery (ERAS) has attracted increasing clinical attention because of its advantages of reducing opioid dosage, shortening oral feeding time, shortening hospital stay, and improving clinical medical quality. Children's ERAS anesthesia management is facing completely different challenges than adult ERAS anesthesia strategies because of the organ structure and function that are still in the stage of growth and development. Therefore, it is important and urgent to standardize the management of ERAS anesthesia in children for pediatric surgery. With reference to the latest literature at home and abroad, and according to the characteristics of clinical diagnosis and treatment practice in China, this consensus has been formulated around preoperative education, preoperative sedation and separation from parents, preanesthesia evaluation, preoperative nutritional evaluation and nutritional support, fasting and drinking time, anesthesia methods and drug selection, anesthesia depth monitoring, airway management strategy, intraoperative fluid management, body temperature management, treatment in anesthesia recovery room, prevention and treatment of complications during recovery period, prevention and treatment of postoperative nausea and vomiting, pain management, early treatment in ward, etc., aiming to attract the attention of anesthesiologists and provide guiding suggestions for anesthesia management of children ERAS in China.

To determine the correlation between the titer of anti-muscle-specific tyrosine kinase (anti-MuSK) antibodies (Abs) and the severity and prognosis of Musk-associated myasthenia gravis (Musk-MG).

A total of 33 MuSK-MG patients diagnosed at Department of Neurology, Peking Union Medical College Hospital from May 2018 to June 2020 were prospectively included. Patients were divided into different groups according to immune state, and the immune naive patients were further divided by the Myasthenia Gravis Foundation of America (MGFA) classification. There were 28 Musk-MG patients who completed the follow-up and subdivided into different groups according to post-intervention status (PIS). Twenty-five patients who received immunotherapy were divided into corticosteroid monotherapy group (n=17) and corticosteroid combined with immunosuppressant group (n=8). The comparison of Ab titers between different MGFA groups and PIS groups was determined by Kruskal-Wallis method, and the comparison of Ab titers between different time points was analyzed by Mann-Whitney U method.

There were 11 males and 22 females included in the study, with an onset age of 48 (18, 73) years, of which 16 cases were immune naive and 17 cases were treated with corticosteroids or immunosuppressant at least once. In immune naive population, a significant difference of Ab titers among different MGFA phenotypes was detected (P=0.04). Ab titers were reduced by immunosuppression therapy (the median value decreased from 1.20 to 0.87, P=0.01). Twenty-four (85.7%) MuSK-MG patients achieved a good prognosis (PIS-PR/MM), 1 (3.6%) case achieved improvement (PIS-I), and 3 (10.7%) patients′ condition worsened (PIS-W), there was no significant difference of Ab titers among the three groups (P=0.21). Meanwhile, there was no significant difference of Ab titers between different treatment groups (P=0.95).

In the immune naive state, the concentration of MuSK-Ab is consistent with the severity of the disease, and the Ab titers decrease after immunotherapy. Change of Ab titers is related to the daily dosage of corticosteroid and is not consistent with PIS grades.

To investigate the factors related to myasthenic crisis (MC) in myasthenia gravis patients (MG) with oropharyngeal involvement during hospitalization.

The clinical data of 99 MG patients with oropharyngeal involvement who were admitted to Beijing Tongren Hospital from 2018 to 2020 were retrospectively reviewed. There were 52 males and 47 females, aged 17-89 (55±15) years old, with a disease duration of 1-240 [10 (4, 36)] months. Multivariable logistic regression analysis was used to determine the factors associated with MC.

A total of 19 (19.19%) patients developed into MC during hospitalization. Multivariate logistic regression analysis showed that age of hospitalization ≥ 60 years old (OR=31.378, 95%CI: 3.868-254.557, P=0.001), type B and C thymoma (OR=29.175, 95%CI: 2.986-285.016, P=0.004), excess oropharyngeal secretions (OR=12.649, 95%CI: 2.057-77.783, P=0.006) and infections (OR=9.539, 95%CI: 1.345-67.645, P=0.024) were independently related to MC in MG patients with oropharyngeal involvement.

Older age, malignant thymoma, excess oropharyngeal secretions and infection are independently related to MC in MG patients with oropharyngeal involvement during hospitalization. Therefore, great attention should be paid to this type of MG patients, and increased oropharyngeal secretions and various infections should be actively treated, so as to reduce the occurrence of MC.

To investigate the characteristics of low frequency repetitive nerve stimulation (RNS) in patients with myasthenia gravis (MG) and analyze the correlation between RNS results and clinical characteristics.

The clinical and electrophysiological data of 107 MG patients who were admitted to Guangdong Provincial People′s Hospital and underwent electromyography (EMG) between September 2015 to September 2020 were retrospectively reviewed. The characteristics of low frequency RNS in ocular MG and generalized MG patients were analyzed. Patients were divided into RNS-negative group and RNS-positive group according to the RNS results. The clinical features, serological and thymic CT findings, thymic pathology were collected and compared. Binary logistic regression analysis was used to analyze the related factors of low frequency RNS.

Generalized MG (73.0%, 46/63) showed a lower positive rate of low frequency RNS compared to ocular MG (34.1%, 15/44) (P<0.001). In generalized MG, the positive rate of low frequency RNS in accessory nerve (68.3%, 43 cases) and facial nerve (52.4%, 33 cases) was higher than that in ulnar nerve (14.3%, 9 cases) (P<0.001). The decrease rate of compound muscle action potential (CMAP) in facial nerve (32%±11%) was higher than that in ocular muscle type (22%±7%) in RNS-positive group (P=0.011). Patients with positive facial nerve RNS were more likely to involve the throat muscles than those with negative result [22 cases (52.4%) compared with 17 cases (26.2%), P=0.006]. RNS-positive group showed a significantly higher quantitative myasthenia gravis (QMG) score than that of negative group (P<0.001). In ocular MG, patients with positive RNS showed a later onset (P=0.021), higher acetylcholine receptor (AChR) antibody-positive rate (P=0.03) and QMG score (P<0.001). Additionally, In generalized MG, patients with positive RNS showed a significantly higher AChR antibody-positive rate (P=0.023) and QMG score (P<0.001). The logistic regression analysis showed that QMG score [OR(95%CI)=1.66(1.36-2.03), P<0.001] and positive AChR antibody [OR(95%CI)=5.45(1.28-23.14), P=0.022] were independently related to abnormal RNS.

Low frequency RNS is more sensitive in generalized MG. The stimulation of facial and accessory nerves increases the positive rate of RNS in MG patients. Abnormal results of low frequency RNS tend to be combined with positive AChR antibody and higher QMG score, reflecting the severity of muscle weakness. Therefore, serological examination and early intervention are required for those with abnormal RNS.

To investigate the diagnostic value of serum lipoprotein associated phospholipase A2 (Lp-PLA2), amyloid A (SAA) and immunoglobulin E (IgE) in patients with type 2 diabetes (T2DM) mellitus complicated with atherosclerotic disease.

From June to December 2019, 224 patients with T2DM in the Second Hospital of Lanzhou University were selected, including 144 males and 80 females, aged (61±11) years. According to the results of imaging examination, the patients were divided into T2DM with AS group (T2DM-AS group, n=160) and T2DM group (n=64); Healthy subjects in the same period were selected as healthy control group (n=160). Lp-PLA2, IgE, SAA, hs-CRP, TC, TG, HDL-C, LDL-C and Hcy were detected in all patients and healthy controls. The correlation between the above indexes, gender, age and T2DM with AS was analyzed; Multivariate logistic regression was used to analyze the risk factors of T2DM with AS.

Compared with the healthy control group, the levels of IgE and Lp-PLA2 in T2DM-AS group and T2DM group were increased, and the levels of SAA in T2DM-AS group were increased (all P<0.05); Compared with T2DM group, the levels of Lp-PLA2, IgE and SAA were increased in T2DM-AS group (allP<0.05). T2DM with AS was positively correlated with age, IgE, Lp-PLA2 and SAA (r=0.468, 0.269, 0.486, 0.418, all P<0.05), and negatively correlated with HDL-C (r=-0.338, P<0.05). Multivariate logistic regression analysis showed that age (OR=0.865, 95%CI: 0.763-0.982, P<0.05), IgE (OR=0.910, 95%CI: 0.840-0.987, P<0.05) and Lp-PLA2 (OR=0.942, 95%CI: 0.910-0.986, P<0.05) were risk factors of T2DM with AS. ROC curve showed that the combined detection of Lp-PLA2, SAA and IgE could improve the diagnostic efficiency of T2DM with AS (AUC=0.895,P<0.05), the sensitivity was 80.0%, and the specificity was 93.7%.

The levels of Lp-PLA2, IgE and SAA increase in T2DM patients with AS. The combined detection of Lp-PLA2, SAA and IgE can improve the diagnostic efficiency of T2DM patients with AS.

To analyze the clinical manifestations and gene mutations of patients with Alagille Syndrome (ALGS) to improve diagnosis and provide a boarder spectrum of gene mutagenesis.

A retrospective study was performed in 18 ALGS patients admitted to Xi′an Children′s Hospital from January 2016 to January 2020. Clinical characteristics, biochemical parameters, gene mutations and prognosis were collected and analyzed. Next-generation sequencing of liver disease-related gene panels or the whole exome was carried out for the probands. Mutations of candidate genes were verified by Sanger sequencing in their family members. Based on the comparison with a well-known database of disease, the harmfulness and structures of proteins with novel mutations were predicted, and the pathogenicity was evaluated.

There were 9 males and 9 females with ALGS in this study, and the age of initial diagnosis was 2.5 (1.9, 6.8) months. All patients initially presented with cholestasis, with other symptoms including 15 cases of special facial features, 11 cases of butterfly vertebrae, 10 cases of congenital heart disease, 5 cases of posterior corneal embryonic ring (among 16 cases with ophthalmological examination), and 1 case of polycystic kidney disease. A total of 14 JAG1 gene mutations and 6 NOTCH2 gene mutations were identified. Among these newly identified mutations, 6 were associated with JAG1 gene, including c.1213delA (p.T405Lfs*7), c.1270dupG(p.A424Gfs*5), c.1741dupG(p.A581Gfs*8), c.3045delC (p.I1016Ffs*20), c.2000-2A>C and c.625C>A(p.H209N); 4 were associated with NOTCH2 gene, including c.6961dupG(p.A2321Gfs*79), c.518G>T(p.G173V), c.6157C>T(p.R2053C) and c.710G>A(p.R237Q). Sixteen patients were followed up for (37.9±31.5) months. Among these cases, 2 died of liver failure (1 case underwent Kasai operation due to misdiagnosis with biliary atresia), 1 improved after liver transplantation, and 13 were in stable condition after medical treatment.

The phenotypes of ALGS are diverse, genetic detection can help diagnosis. The JAG1 and NOTCH2 genes showed a wide array of mutations, with many novel mutations identified in this study.

To quantitatively analyze the reticulin fiber intensity density (RFD) in patients with myelodysplastic syndrome (MDS) by using the computer-aided grid point method, and preliminarily explore its correlation with the prognosis of MDS patients.

Bone marrow (BM) slices from 32 primary MDS patients treated in Tongren Hospital Shanghai Jiao Tong University School of Medicine from February 2017 to December 2019 were observed. Images were taken by the optical microscope imaging system after the Gomori staining. The computer grid marking software was developed according to the principle of the mesh micrometer to assess RFD, meanwhile, the artificial semi-quantitative were used to assess the fibrosis of bone marrow. The co-relation between the above two methods was evaluated, and the relationship between RFD and prognosis of MDS patients were further investigated with Cox regression analysis.

Of the patients, there were 17 males and 15 females with a median age of 69 years (32-91 years). The RFD quantitatively analyzed by the computer-based method was positively correlated with the myelofibrosis grade by the artificial semi-quantitative analysis (r=0.497, P=0.004). The RFD in patients diagnosed with MDS complicated with excess blasts (MDS-EB) was significantly higher than that in the non-MDS-EB group((9.55%±0.75%) vs (1.71%±0.23%), P<0.001). Cox regression model analysis showed that the RFD of MDS patients had better prognostic value when compared with the artificial semi-quantitative analysis, which was also a poor prognostic factor (RR=1.337, 95%CI: 1.085-1.648, P=0.006). The overall survival (OS) of patients with RFD>5.54% was significantly shorter than that with RFD≤5.54% (P=0.001). The OS of MDS-EB patients with RFD>9.81% was significantly shorter than that in patients with RFD≤9.81% (P=0.003).

Abnormal proliferative fibrosis of bone marrow is a potential high-risk factor for poor prognosis of MDS patients.

To establish the standard operation procedure (SOP) for detection of oligoclonal band (OCB) in cerebrospinal fluid (CSF) and verify consistency by using this SOP in different laboratories.

The SOP for detection of CSF-OCB fluid was successfully established by an expert feedback approach. Neuroimmunology laboratories in 3 representative Chinese three-tier research hospitals were selected for this study, and commercially available protein electrophoresis automation systems and detection SOP were set up. The quality control product was provided by the College of American Pathologists (CAP) and Sebiacompany were used for interior quality and compared to each other, respectively. Seventeen serum and CSF paired samples were tested and compared using the same SOP. Kappa test or Kendall W test were adopted to evaluate the inter-laboratory consistency among different hospitals.

The results of repeated testings in a single hospital suggested that the 2-and 4-fold dilution for CSF-OCB were reported as positive, while 64-and 128-fold dilution were reported as negative. Positive or negative inconsistencies were reported in 8-, 16-, and 32-fold dilution. After increasing the number of repetitions, the results showed that both 16-and 32-fold dilution were reported as negative, and 8-fold dilution exhibited negative results (2 positive results for 40 repetitions, coincidence rate=95%).The results of multi-center inter-laboratory quality assessment showed that the detection consistency rate among 3 hospitals was 100% (Kappa value =1).

The SOP to detect CSF-OCB established in this study demonstrates a good repeatability and stability. Therefore,such SOP would be a good reference for diagnostic laboratories to detect CSF-OCB in China.

To establish a nomogram model for hematoma expansion (HE) prediction after intracerebral hemorrhage (ICH) and evaluate its performance in a multidimensionally way.

A total of 348 ICH patients who were firstly diagnosed and hospitalized in the Second Affiliated Hospital of Soochow University from January 2017 to December 2019 were collected retrospectively. There were 236 males and 112 females, and their age ranged from 18 to 94 (62.0±14.6) years. All patients were divided into HE group (n=121) or non-HE group (n=227) according to the presence or absence of HE. The clinical and imaging features were compared between the two groups. Multivariate logistic regression analysis was performed for determining the independent predicting factors for HE prediction and a Nomogram model was established by using these factors. Receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the prediction effectiveness, accuracy and clinical practicability of the model, respectively. Bootstrap method was used for internal validation.

There were significant differences in onset time, swirl sign, history of anticoagulants administrations, systolic blood pressure when admission, Glasgow coma scale (GCS) scores and RBC distribution width between the two groups[(1.77(1.0, 2.5) h vs 2(1, 3) h, 72 cases (59.5%) vs 94 cases (41.4%), 17 cases (14.0%) vs 15 cases (6.6%), (170.69±29.19) mmHg(1 mmHg=0.133 kPa) vs (163.84±26.07) mmHg, 11(8, 14) scores vs 14(10, 15) scores, 44.3% (41.2%, 46.8%) vs 42.4% (40.1%, 45.3%);respectively, all P<0.05]. Multivariate logistic regression analysis demonstrated that onset time (OR=0.809, 95%CI: 0.682-1.961, P=0.015), swirl sign (OR=0.562, 95%CI:0.349-0.905, P=0.018), history of anticoagulants administrations (OR=0.394, 95%CI: 0.180-1.861, P=0.020), and GCS (OR=0.881, 95%CI: 0.815-1.952, P=0.001) were the predicting factors for HE. The area under the curve (AUC) of the Nomogram model was 0.735(95%CI: 0.687-0.805), which demonstrated that the model has an ideal prediction effectiveness. The calibration curve showed that the prediction probability of HE of the model fits well with the actual probability, and with high calibration. DCA showed relatively wide range of optional threshold probability of the model (ranging from 14% to 72%), the clinical practicability of this model was high. The internal validation results showed a C-index of 0.703, indicated a good discrimination power.

The established Nomogram model can predict the HE of ICH with good prediction effectiveness, discrimination power and with good clinical practicability, which can be capable of providing an intuitive and visual guidance tool for timely identifying ICH patients who may have HE.

To characterize the antibiotic resistance and virulence in a carbapenem-resistant Klebsiella pneumoniae (CRKP).

A CRKP (designated K. pneumoniae C35) was isolated from a stool sample. The minimal inhibitory concentrations of antimicrobial agents were determined using the broth microdilution method. Whole-genome sequencing and genome analysis were performed to identify the antibiotic resistance and virulence genes. The genetic relationship among K.pneumoniae C35 and other CRKP isolates from our hospital was analyzed by single nucleotide polymorphism (SNP) typing of core genomes. Conjugation experiments were carried out by filter mating to evaluate the transferability and efficiency of resistance genes. The virulence phenotype was determined by Galleria mellonella infection model.

K. pneumoniae C35 exhibited resistance to the majority of tested antibiotics, especially carbapenems, sulbactam, and polymyxins. SNP typing showed that K. pneumoniae C35 shared a high degree of sequence homology with several CRKP isolates from different wards. This ST11 CRKP carried 13 resistance genes, including bla_KPC-2, bla_CTX-M-199, mcr-1, and tet(A) variant. bla_KPC-2 gene was located on an IncFⅡ plasmid with>69 800 bp in size,bla_CTX-M-199 and mcr-1 genes were located on an IncI2 plasmid (>64 800 bp), andtet(A) variant was located on an unknown Inc-type plasmid (83 628bp). All these three plasmids were conjugative. K. pneumoniae C35 was found to harbor rmpA, rmpA2, and iucABCD aerobactin-related genes, and was considered to be classic carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP). The virulence potential of this strain was confirmed in a Galleria mellonella infection model. The survival rate of the larvae injected with strain C35 at 48 h after infection was significantly lower than that of negative control strain (16.7% vs 80.0%).

Multiple conjugative plasmids are identified in a faecal CR-hvKP. The IncI2 plasmid co-carrying both bla_CTX-M-199 and mcr-1 genes is firstly identified in CR-hvKP. The emergence of such strain should be alerted and active surveillance is warranted.

Adenosine deaminase 2 deficiency syndrome is a rare autosomal recessive disease. This paper reports a patient with adult onset, whose main clinical manifestations were skin rash and thrombocytopenia, accompanied by immunodeficiency, and whose disease was prolonged and complicated. The diagnosis was confirmed by clinical analysis, skin pathology, serum enzymology and gene sequencing.

This paper reports two cases of topical use of botulinum toxin (BTX) in myasthenia gravis (MG). One case was clinical symptoms of subclinical MG induced by BTX, and the other case was safe and effective when the MG condition was stable. The case proved from both positive and negative aspects that BTX should be prohibited during the active stage of MG; When the patient's MG condition is stable, topical use of BTX due to comorbidities can benefit patients with MG.

Drinking alcohol can not only damage the upper gastrointestinal tract, but also cause colorectal lesions. This paper reports the pathological characteristics of two cases of alcohol-related colorectitis and its differential diagnosis from inflammatory bowel disease and ischemic bowel disease, aiming at improving the attention of pathologists to this lesion and making a correct diagnosis.

Myasthenia gravis has greater heterogeneity. Previous treatments are based on progressive strategies, which are difficult for refractory patients to benefit from, and there are already many complications when considering escalating immunotherapy. Therapeutic goals and the emergence of fast-acting therapies have changed therapeutic strategies. Combining the progressive strategy and the rapid onset strategy to form an individualized treatment pathway helps to obtain and maintain good and stable efficacy as early as possible.

CT angiography (CTA) spot sign is associated with hematoma enlargement, mortality and poor functional prognosis in patients with spontaneous supratentorial cerebral hemorrhage. However, there are no related studies to explore the relationship between spot sign and spontaneous cerebellar hemorrhage. To investigate the correlation between spot sign and hematoma enlargement, 90-day mortality, and functional prognosis in spontaneous cerebellar hemorrhage, the researchers collected relevant clinical data of 358 patients with spontaneous cerebellar hemorrhage in three teaching hospitals from 2002 to 2017 (a modified Rankin scale score of 4 to 6 points was defined as poor functional prognosis). The results showed that 181 (51%) of 358 patients with spontaneous cerebellar hemorrhage had CTA examination. Of these 181 patients, 121 (67%) were treated conservatively and 60 (33%) surgically. Fifteen (12%) of conservatively treated patients developed spotty signs, with larger hematoma volumes in patients with spotty signs (P=0.001), and the hematoma expanded faster (P=0.034）。 Multivariate logistic regression analysis showed that the spot sign was independently associated with 90-d case mortality (OR=7.6， 95%CI：1.6~88.0，P=0.037）。 whereas of the surgically treated patients, 14 (23%) developed spotty signs, and the patients who developed spotty signs were older (P=0.047), with more female patients (P=0.033）。 Multivariate logistic regression analysis also showed that the spot sign was independently associated with 90-day mortality (OR=2.1， 95%CI：1.1~4.3，P=0.033）。 The results of this study showed that in patients with spontaneous cerebellar hemorrhage treated conservatively, spotty sign was associated with the speed of hematoma expansion, mortality and poor functional prognosis; Whereas in surgically treated patients, the spotty sign was associated with 90-d mortality.

Most studies have shown that there is no significant correlation between anti-acetylcholine receptor antibody (AChR-Ab) titer and the severity of myasthenia gravis (MG), but can AChR-Ab levels in MG patients be used to monitor changes in MG disease or predict MG prognosis? This study investigated the relationship between drug-induced changes in AChR-Ab levels and MG prognosis in patients with MG after 1 year of immunosuppressive therapy. The study included 53 AChR-Ab-positive MG patients admitted to Chiba University Affiliated Hospital in Japan from January 2013 to December 2018. AChR-Ab was re-tested within 100 days after immunosuppressive therapy, and the detection time was 71 (55~84) days. The AChR-Ab level reduction rate (RR-AChR-Ab, %/d) was adjusted for the time between initiation of treatment, and the AChR-Ab level remeasurement was calculated as follows: (pre-treatment-post-treatment AChR-Ab level) /pre-treatment AChR-Ab level/number of days from initiation of treatment, resulting AChR-Ab level remeasurement ×100. Subjects were divided into two groups based on cutoff values for RR-AChR-Ab, and subject profiling was used to determine the status of achieving minimum performance (MM) or better after 1 year of immunosuppressive therapy. The post-intervention status and MG activity of daily living (MG-ADL) scores of the American Myasthenia Gravis Foundation after 1 year of treatment were compared between the two groups. The results of this study showed a cut-off value of 0.64%/d for RR-AChR-Ab. A higher proportion of MG patients in the high RR-AChR-Ab group achieved MM or better (90% versus 65%,P=0.03), and the MG-ADL score was lower (median 1 to 2,P=0.04), which was lower than the low RR-AChR-Ab group. Kaplan-Meier analysis showed that the high RR-AChR-Ab group was prone to reach MM early (P=0.002, log-rank Inspection). Therefore, the study concluded that high RR-AChR-Ab is associated with a good prognosis 1 year after treatment. Re-measuring AChR-Ab within 100 d of treatment may be useful in predicting the prognosis of AChR-Ab positive MG 1 year after treatment.