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@#Objective To investigate the clinical characteristics and gene mutations of late-onset methylmalonic aciduria with homocysteinemia. Methods We retrospectively analyzed the clinical data and genetic test result of one patient with late-onset cblC-type methylmalonic aciduria with homocysteinemia arising from MMACHC gene mutation. Relevant literature was reviewed. Results This male patient initially presented with numbness in both feet, and gradually developed stiffness and weakness in both lower limbs, with nonspecific mental and behavioral symptoms before onset. Gene testing detected a missense mutation, c.482G>A(p.Arg161Gln) in exon 4 of the MMACHC gene. It was a homozygous mutation, which was different from compound heterozygous mutations of c.482G>A reported in previous literature. Conclusion Methylmalonic aciduria with homocysteinemia is clinically heterogeneous, with a high possibility of a missed diagnosis or misdiagnosis. The diagnosis should be considered in the presence of mental and behavioral abnormities of unknown cause. Gene detection is an important basis for the diagnosis and typing of the disease.
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Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.
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Lactente , Recém-Nascido , Masculino , Humanos , Feminino , Permeabilidade do Canal Arterial/tratamento farmacológico , Recém-Nascido Prematuro , Estudos Transversais , Ibuprofeno/uso terapêutico , Recém-Nascido de muito Baixo Peso , Síndrome da Persistência do Padrão de Circulação Fetal , Doenças do Prematuro/terapiaRESUMO
OBJECTIVES@#To evaluate the early risk factors for death in neonates with persistent pulmonary hypertension of the newborn (PPHN) treated with inhaled nitric oxide (iNO).@*METHODS@#A retrospective analysis was performed on 105 infants with PPHN (gestational age ≥34 weeks and age <7 days on admission) who received iNO treatment in the Department of Neonatology, Children's Hospital of Nanjing Medical University, from July 2017 to March 2021. Related general information and clinical data were collected. According to the clinical outcome at discharge, the infants were divided into a survival group with 79 infants and a death group with 26 infants. Univariate and multivariate Cox regression analyses were used to evaluate the risk factors for death in infants with PPHN treated with iNO. The receiver operating characteristic (ROC) curve was used to calculate the cut-off values of the factors in predicting the death risk.@*RESULTS@#A total of 105 infants with PPHN treated with iNO were included, among whom 26 died (26/105, 24.8%). The multivariate Cox regression analysis showed that no early response to iNO (HR=8.500, 95%CI: 3.024-23.887, P<0.001), 1-minute Apgar score ≤3 points (HR=10.094, 95%CI: 2.577-39.534, P=0.001), a low value of minimum PaO2/FiO2 within 12 hours after admission (HR=0.067, 95%CI: 0.009-0.481, P=0.007), and a low value of minimum pH within 12 hours after admission (HR=0.049, 95%CI: 0.004-0.545, P=0.014) were independent risk factors for death. The ROC curve analysis showed that the lowest PaO2/FiO2 value within 12 hours after admission had an area under the ROC curve of 0.783 in predicting death risk, with a sensitivity of 84.6% and a specificity of 73.4% at the cut-off value of 50, and the lowest pH value within 12 hours after admission had an area under the ROC curve of 0.746, with a sensitivity of 76.9% and a specificity of 65.8% at the cut-off value of 7.2.@*CONCLUSIONS@#Infants with PPHN requiring iNO treatment tend to have a high mortality rate. No early response to iNO, 1-minute Apgar score ≤3 points, the lowest PaO2/FiO2 value <50 within 12 hours after admission, and the lowest pH value <7.2 within 12 hours after admission are the early risk factors for death in such infants. Monitoring and evaluation of the above indicators will help to identify high-risk infants in the early stage.
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Criança , Humanos , Lactente , Recém-Nascido , Administração por Inalação , Hipertensão Pulmonar/tratamento farmacológico , Óxido Nítrico , Síndrome da Persistência do Padrão de Circulação Fetal/tratamento farmacológico , Estudos Retrospectivos , Fatores de RiscoRESUMO
The amorphous solid dispersion is one of the most effective formulation approaches to enhance the oral bioavailability of poorly water-soluble drugs. However, the amorphous drugs tend to crystallize during storage or dissolution due to inadequate formulations, preparation techniques, storage and dissolution conditions, thus negating their advantages. Meanwhile, it is often difficult to establish in vitro-in vivo correlation for amorphous solid dispersions owing to the difference between dissolution media and physiological environments and between the apparent concentration and membrane transport flux, the dynamic process of the in vivo absorption, which put great challenges to the development of amorphous solid dispersion products. This review covers the recent progress on the mechanistic study of the in vitro dissolution and in vivo absorption of amorphous solid dispersions, aiming to provide guidance for the formulation development of poorly soluble drugs.
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Objective:To evaluate the mixed team-based learning (TBL) teaching method in the practical teaching of critical obstetric diseases.Methods:A total of 72 undergraduate students majoring in "5+3" clinical medicine who practiced in The First Affiliated Hospital of Chongqing Medical University from April to June 2019 were selected in the study. The typical cases of obstetric critical illness were selected, and the students were taught by TBL teaching combined with flipped classroom. After the class, a questionnaire survey was conducted to evaluate the teaching effect.Results:Totally 72 questionnaires were recovered and the results showed that all the students thought this kind of mixed TBL teaching method was helpful to develop clinical thinking ability, and the process of "group discussion" and "extra-curricular preparation" was very helpful to understand the learning. A percentage of 93 (67/72) of the students liked this teaching mode, while 28% (20/72) of the students thought this learning mode was very stressful.Conclusion:This mixed TBL teaching method is effective and feasible in the practical teaching of critical obstetric diseases.
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Objective:To investigate the effects of cervical plexus block anesthesia combined with general anesthesia on subtotal thyroidectomy in patients with hyperthyroidism and stress response.Methods:A total of 68 patients with hyperthyroidism who underwent subtotal thyroidectomy in Zhangjiagang City Hospital of Traditional Chinese Medicine, Jiangsu Province, from January 2018 to January 2021 were selected as observation subjects, and were divided into control group and observation group according to the random number table method, both of which were 34 cases. Patients in control group were given general anesthesia, and the observation group was given cervical plexus block anesthesia combined with general anesthesia. The heart rate and mean arterial pressure before anesthesia (T0), immediately before intubation (T1), immediately after intubation (T2), and at the end of surgery (T3), the time of awakening and extubation after surgery, the visual analog score (VAS) of pain at 1, 4, 12, and 24 hours after surgery, stress response of before and 24 hours after surgery, and complications after surgery were compared between the two groups.Results:There was no significant difference in heart rate and mean arterial pressure between the two groups at T0 ( P > 0.05); the heart rate and mean arterial pressure at T1 were lower than those at T0 in the same group ( P < 0.05); the heart rate and mean arterial pressure at T2 and T3 in the control group were higher than those at T0 in the same group ( P < 0.05); the heart rate and mean arterial pressure at T2 and T3 in the observation group did not change significantly compared with those at T0 in the same group ( P > 0.05), but were lower than those in the control group at the same time ( P < 0.05). The awakening time and extubation time of patients in the observation group were shorter than those in the control group ( P < 0.001). The VAS scores of patients in the observation group were lower than those in the control group at 4, 12 and 24 hours after surgery ( P < 0.001). The serum norepinephrine (NE) and cortisol (COR) levels of patients in the two groups at 24 hours after surgery were higher than those before surgery, and the levels in the observation group were lower than those in the control group at the same time ( P < 0.05). The total incidence of postoperative complications in the observation group (8.82%, 3/34) was lower than that in the control group (29.41%, 10/34, χ 2 = 4.66, P = 0.031). Conclusion:Cervical plexus block anesthesia combined with general anesthesia has a good effect on subtotal thyroidectomy in patients with hyperthyroidism, which can speed up the patients' awakening, reduce complication, and has little impact on stress response.
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Objective:To summarize the clinical manifestation and imaging of superficial siderosis of the central nervous system and explore the potential etiology.Methods:The clinical and imaging data of 7 patients diagnosed as superficial siderosis of the central nervous system in Peking Union Medical College Hospital from May 2013 to November 2019 were retrospectively reviewed. The etiology and follow-up prognosis through phone call were analyzed.Results:There were 7 patients included (3 male and 4 female) with an average age of 53 years (41-58 years). The cardinal manifestations were sensorineural deafness (all 7 cases), cerebellar ataxia (all 7 cases) and pyramidal signs (all 7 cases). Dizziness (6 cases), bladder disturbance (5 cases), headache (3 cases), double vision (2 cases) and congnitive impairment (1 case) could also happen. Magnetic resonance imaging showed symmetrical well-defined curvilinear homogeneous low signal on T 2 or blood-sensitive sequences (T 2* gradient echo or susceptibility-weighted imaging) over the superficial surface of cerebellar, brain stem, and spinal cord or cranio-cervical junction. All the 7 patients showed cerebellar atrophy especially the upper vermis. The potential causes included trauma history in 3 cases, intraspinal fluid-filled collection which indicated dural defect or duropathologies in 3 cases, intraspinal mass in 1 case and vertebral and disc degeneration in all 7 patients. The 5 patients who successsfully got follow-up showed exacerbation of variable degree. Conclusions:Classical superficial siderosis of the central nervous system is a rare disease with cardinal manifestation of progressive ataxia, sensorineural deafness and pyramidal signs. T 2WI of magnetic resonance imaging showing low signal over the superficial surface of cerebellar, brain stem, and spinal cord could indicate the diagnosis, and blood-sensitive sequences such as T 2* gradient echo or susceptibility-weighted imaging were more sensitive. Duropathologies or dural defect may be the most probable causes of the disease and should be examined and treated carefully.
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@#Objective To analyze the feasibility of using triangular-sail technique that allows intermittent two-lung ventilation during minimally invasive coronary artery bypass grafting (MICS CABG). Methods The clinical data of 207 patients with MICS CABG in our cardiac center from January 2019 to November 2020 were retrospectively analyzed. These patients were divided into two groups. A group OLV included 111 patients who underwent one-lung ventilation during surgery, while a group TLV included 96 patients who underwent intermittent two-lung ventilation. The triangular-sail technique was used in the group TLV. This simple technique isolated the operative field from lung lobes with the traction of pericardial adipose tissue. The preoperative data and perioperative clinical data of the two groups were compared and analyzed. Results There was no statistical difference in basic preoperative data between the two groups. The operation time in the OLV group was shorter than that in the TLV group (296.7±57.3 min vs. 334.1±87.0 min, P=0.000), and the duration of postoperative mechanical ventilation and ICU stay were not statistically different between the two groups. There was also no statistical difference in the incidence of pneumothorax or atelectasis between the two groups. Conclusion The triangular-sail technique is simple and easy to implement. The technique allows intermittent two-lung ventilation during MICS CABG procedure.
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A 57-year-old man was admitted to hospital with diarrhea for 10 months and dizziness for 4 months. The patient had 1-2 liters watery stool per day, without pyogenic blood or abnormality in gastroenteroscopy examination. The level of hemoglobin and albumin was generally normal, and fasting test was positive. At the same time, he was accompanied with hyperalgesia of lower limbs and orthostatic hypotension. After the discussion of multiple disciplinary teams, the patient was diagnosed with amyloidosis by sural nerve biopsy, myocardial MRI, and the assays of urine immunoelectrophoresis and serum free light chain. Light chain amyloidosis was confirmed after excluded the diagnosis of familial amyloidosis. The patient was improved after courses of chemotherapy with melphalan and dexamethasone.
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Chronic obstructive pulmonary disease (COPD) is a common preventable disease characterized by persistent respiratory symptoms and airflow limitation, mainly manifested as chronic cough, expectoration and wheezing. With the aging of the population and the aggravation of environmental pollution, the number of elderly patients with COPD has gradually increased in recent years. Compared with young individuals, the acute exacerbation of elderly COPD patients is more frequent and often complicated with a variety of underlying diseases, even after active drug treatment, the therapeutic effect is still limited. More systematic treatment methods are needed on the basis of conventional drug therapy. The positive role of pulmonary rehabilitation in COPD patients who are in stable period has been confirmed, but in the acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients is controversial, especially in the elderly AECOPD patients. In this review, we summarized current studies of the application of pulmonary rehabilitation in elderly AECOPD patients.
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Objective:To discuss the clinical features and treatment of 19 patients with granulomatosis with polyangiitis (GPA) complicated with hypertrophic cranial pachymeningitis (HCP).Methods:The clinical features of 19 patients diagnosed with GPA complicated with HCP in Peking Union Medical College Hospital were retrospectively analyzed.Results:Among the 315 patients with GPA, 19 (12 males, 7 females, with) were diagnosed with HCP at Peking Union Medical College Hospital. The median age was 57 (19-64) years. In the neurological manifestations per se, all patients had headache, 16 patients had cerebral involvement, which included 8 cases at the frontal area, 8 cases at the temporal area, 8 cases at the skull base area (4 cases with parasellar involvements including 3 cases with cavernous sinus involvement and 2 cases with orbital involvement), 6 cases of tentorium involvement, 2 cases of cerebral palsy, 1 case of calvarium, 1 case of occipital, and 1 case with combined spinal pachymeningitis, respectively. In systemic manifestations, 10 patients had fever, 8 patients had weight lose, 4 patients had lung involvement, 3 patients had kidney involvement, 16 patients had nasosinusitis, 10 patients had tympanitis, and 16 patients had localized GPA. The laboratory tests showed that 15 patients had positive anti-neutrophil cytoplasmic antibodies (ANCA), including 8 cases with positive proteinase 3 (PR3)-ANCA and 6 cases with positive myeloperoxidase (MPO)-ANCA. Sixteen patients had lumbar puncture examination, 9 cases had elevated cerebrospinal pressure, 10 cases had elevated level of protein in cerebrospinal fluid. Nineteen patients were treated with glucocorticoids (12 patients accepted pulse therapy) and immunosuppressive agents. Twelve patients were treated with intrathecal injections of dexamethasone combined with or without Methotrexate (MTX). All 19 patients were improved.Conclusion:HCP, as a rare but serious manifestation of GPA, is not rare in active cases and should be intensively treated.
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Objective:Based on the perspective of supply and demand balance, to analyze the implementation effects of primary-feature medical services measures in medical alliances.Methods:From July to September 2019, two regions with different levels of economic development were chosen, and from each region one leading hospital and two community health service centers/township hospitals were selected from its medical alliance. A total of 213 medical staff and 703 residents were surveyed, to learn their awareness and performance appraisal of these feature services.Frequency and proportion were calculated in a descriptive statistical analysis. The scores of the performance appraisal of both supply and demand sides were tested by independent sample t. Results:In the performance appraisal of such measures, the average scoring by medical staff was 4.39±0.07, and that by residents was 3.85±0.06; the residents were more concerned with service capabilities and contents, while medical staff were more concerned with service content and delivery mode; supply and demand sides were found with consensus in terms of improving the medical service quality of chronic diseases in primary level and service accessibility.Conclusions:The county-level medical alliances should focus on enhancing their capacity of primary medical services, and improving their primary service mode with the help of medical insurance institutions. Meanwhile, it is imperative to optimize the primary medical service policy in view of supply and demand balance.
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Objective: To improve the understanding of rare anti-myelin-associated glycoprotein (MAG) positive IgM monoclonal gammopathy related peripheral neuropathy (IgM-PN) . Methods: Eleven cases of IgM paraproteinemia and anti-MAG antibody positive neuropathy diagnosed since 2014 in Peking Medical Union College Hospital were summarized. The medical records including clinical manifestation, lab results, treatment and prognosis were analyzed. Results: Among the 11 patients (8 male and 3 female) , the median onset age is 63 years old (range from 52 to 77 years old) . The peripheral neuropathy of 9 patients were characterized by distal onset of numbness, 6 patients suffered from muscle weakness. The nerve conduction velocity study indicated that all 11 patients had demyelinating peripheral nerve damage, which was sensory predominant and more severe in lower limbs, 6 of them had secondary axonal damage. Monoclonal IgM gammopathy was identified in all 11 patients, among which 6 were IgM κ, 2 IgG κ and IgM κ bi-clonal, 3 IgM λ. Three patients were diagnosed with Waldenström's macroglobulinaemia. The anti-MAG-IgM antibody was positive in all 11 cases. After diagnosis, 9 patients received combination chemotherapy including rituximab or rituximab treatment alone. The monoclonal IgM level declined significantly in 7 patients. The neuropathy was stable or improved. Conclusions: Anti-MAG antibody positive IgM-PN is a rare M protein related disease. In peripheral neuropathy with undetermined etiology, we suggest to screen M protein and anti-MAG antibody. Chemotherapy including rituximab or rituximab alone is recommended as first-line therapy.
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Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autoanticorpos , Imunoglobulina M , Paraproteinemias , Doenças do Sistema Nervoso Periférico , Macroglobulinemia de WaldenstromRESUMO
Objective To evaluate the effect of aerobic exercise combined with resistance exercise on blood sugar and constitution in patients with type 2 diabetes mellitus.Methods Fifty eligible subjects in community type 2 diabetes database were randomly selected and a model intervention group of"1+2+1" was established.The regular exercise intervention was conducted for six months by combining aerobic exercise with resistance exercise.The fasting blood sugar,blood pressure,heart rate,body mass and fat mass before and after intervention were compared by paired t test.Changes in related physical indicators.Results After 6 month of exercise therapy,fasting blood glucose of subjects reduced from (8.58±4.40) mmol/L to (6.29 ±1.72) mmol/L(P=0.032).Body weight also reduced from (62.44±7.35) Kg to (60.70±7.54) Kg(P=0.008). In physical quality related indexes, fat mass decreased significantly, while protein content increased significantly.There were no changes in muscle mass and fat free body weight.In addition, grip strength and flexion range of subjects significantly increased after exercise therapy.Comprehensive score of physical quality of subjects increased from (73.25± 5.65) to (75.48± 5.04) ( P=0.010).Conclusion Exercise therapy of aerobic exercise combined with resistant exercise can effectively reduce blood glucose, body weight and fat mass,increase muscle strength,flexibility and physical quality.This also reflects that the community?led "health and physical integration" mode of work is an effective means to manage chronic diseases and enhance the physical fitness of residents.
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Objective To establish a test of autoantibody-panel for the diagnosis of autoimmune cerebellitis (AC) and determine the prevalence of AC in patients with cerebellar ataxia of unknown etiology.Methods Autoantibody screening tests with indirect immunofluorescence were performed in serum and cerebrospinal fluid (CSF) samples of 400 previously'idiopathic'Chinese patients with cerebral ataxia (inpatients and outpatients in Peking Union Medical College Hospital or referred from hospitals of Beijing Encephalitis Group from 2016 to 2018).Immunotherapy was given to autoantibody positive patients and the effectiveness of immunotherapy was assessed.Detailed AC autoantibodies panel included anti-glutamate decarboxylase 65 (GAD65) antibody,anti-Tr (delta notch-like epidermal growth factor-related receptor (DNER)) antibody,anti-zinc finger protein 4 (ZIC4) antibody,anti-inositol 1,4,5-trisphosphate receptor 1 (ITPR1) antibody,anti-homer protein homolog 3 (Homer 3) antibody,anti-neurochondrin (NCDN) antibody,anti-carbonic anhydrase-related protein (CARP) antibody and anti-Purkinje cell antibody 2 (PCA2) antibody.Results Eight out of 400 (2%) ataxia patients were positive for this AC panel tests,of whom two were positive for anti-GAD65 antibody,two for anti-Tr antibody,one for anti-PCA2 antibody,one for anti-Homer 3 antibody and two were positive for serum anti-NCDN antibody.Autoantibodies against ZIC4,ITPR1 and CARP were not detected in this cohort.Two of the eight ataxia patients also presented with limbic encephalitis,and only one anti-GAD antibody patient was screened with underlying small cell lung carcinoma (SCLC).All the eight patients received immunotherapy and four experienced partial response.Conclusions Autoimmune cerebellitis is the cause of acquired cerebellar ataxia.Tests of autoantibodies associated with AC have diagnostic value for paraneoplastic and non-paraneoplastic cerebellar ataxia.Immunotherapy may yield partial response in patients with AC.
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In view of the recent advancements in the standardized neurology residency training in China, standardized neurology fellowship training has become a crucial next step for China′s graduate medical education. The design of the fellowship and development of relevant norms and standards to ensure quality training constitute key areas in need of further consideration. The United States has established a standardized neurology fellowship training for nearly 30 years and has been successful in ensuring high quality physician training. Currently there are 9 accreditation council for graduate medical education (ACGME) accredited neurology fellowship programs in the USA, including clinical neurophysiology, pain medicine, neurodevelopmental disabilities, vascular neurology, neuromuscular medicine, sleep medicine, endovascular surgical neuroradiology, epilepsy and brain injury medicine. Among them, the number of fellowship training programs in vascular neurology, clinical neurophysiology, and epilepsy are relatively stable or show continuous growth, while neurodevelopmental disabilities and brain injury medicine remain stagnant or even retrogressive. It indicates that design of the neurology fellowship training calls for full weight of a wide array of factors, taking into account the number of subspecialty patients, clinical applications, prospects for future development of the subspecialties, and lessons learned from the United States. We can start with ACGME accredited steady growth fellowship programs and then add others in the future accordingly.
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In view of the recent advancements in the standardized neurology residency training in China, standardized neurology fellowship training has become a crucial next step for China′s graduate medical education. The design of the fellowship and development of relevant norms and standards to ensure quality training constitute key areas in need of further consideration. The United States has established a standardized neurology fellowship training for nearly 30 years and has been successful in ensuring high quality physician training. Currently there are 9 accreditation council for graduate medical education (ACGME) accredited neurology fellowship programs in the USA, including clinical neurophysiology, pain medicine, neurodevelopmental disabilities, vascular neurology, neuromuscular medicine, sleep medicine, endovascular surgical neuroradiology, epilepsy and brain injury medicine. Among them, the number of fellowship training programs in vascular neurology, clinical neurophysiology, and epilepsy are relatively stable or show continuous growth, while neurodevelopmental disabilities and brain injury medicine remain stagnant or even retrogressive. It indicates that design of the neurology fellowship training calls for full weight of a wide array of factors, taking into account the number of subspecialty patients, clinical applications, prospects for future development of the subspecialties, and lessons learned from the United States. We can start with ACGME accredited steady growth fellowship programs and then add others in the future accordingly.
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Objective@#To improve the understanding of rare anti-myelin-associated glycoprotein (MAG) positive IgM monoclonal gammopathy related peripheral neuropathy (IgM-PN) .@*Methods@#Eleven cases of IgM paraproteinemia and anti-MAG antibody positive neuropathy diagnosed since 2014 in Peking Medical Union College Hospital were summarized. The medical records including clinical manifestation, lab results, treatment and prognosis were analyzed.@*Results@#Among the 11 patients (8 male and 3 female) , the median onset age is 63 years old (range from 52 to 77 years old) . The peripheral neuropathy of 9 patients were characterized by distal onset of numbness, 6 patients suffered from muscle weakness. The nerve conduction velocity study indicated that all 11 patients had demyelinating peripheral nerve damage, which was sensory predominant and more severe in lower limbs, 6 of them had secondary axonal damage. Monoclonal IgM gammopathy was identified in all 11 patients, among which 6 were IgM κ, 2 IgG κ and IgM κ bi-clonal, 3 IgM λ. Three patients were diagnosed with Waldenström’s macroglobulinaemia. The anti-MAG-IgM antibody was positive in all 11 cases. After diagnosis, 9 patients received combination chemotherapy including rituximab or rituximab treatment alone. The monoclonal IgM level declined significantly in 7 patients. The neuropathy was stable or improved.@*Conclusions@#Anti-MAG antibody positive IgM-PN is a rare M protein related disease. In peripheral neuropathy with undetermined etiology, we suggest to screen M protein and anti-MAG antibody. Chemotherapy including rituximab or rituximab alone is recommended as first-line therapy.
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Objective To investigate the clinical and electrophysiological characteristics of anti-myelin-associated glycoprotein (MAG)-associated peripheral neuropathy, as well as its antibody detection methods, treatment and prognosis. Methods Six cases of IgM paraproteinemia and anti-MAG antibody-associated peripheral neuropathy were summarized. All of the patients came from Peking Union Medical College Hospital and Qilu Hospital since April 2014 to February 2018. The clinical features, electrophysiological characteristics, and auxiliary examinations including anti-MAG antibody results were analyzed, and the treatment and prognosis were followed. Results Of the six patients, five were male and one was female. The age of onset was 50-77 years and the duration was three months to six years. All the six cases suffered from numbness of distal limbs and gradually progressed to the proximal limbs, of which three cases had muscle weakness. Walking instability occurred in five cases. One patient had electricity-like pain in the lower extremities. Reflexes in the four limbs decreased in five cases, and gloves and socks-like deep sensation decreased in six cases. Five patients underwent lumbar puncture and the cerebral spinal fluid protein ranged from 0.75 to 1.33 g/L. Serum monoclonal proteins were found in six patients, of which four were IgM kappa and two were IgG kappa and IgM kappa biclonal. Four cases were diagnosed with monoclonal gammopathy of undetermined significance and two cases were diagnosed with Waldenstr?m's macroglobulinaemia. Abnormal electromyography was detected in all the six cases, suggesting demyelinating peripheral nerve damage with secondary axonal damage, which was sensory predominant and more severe in lower limbs than upper limbs. In all the six cases, anti-MAG-IgM antibodies were all positive by indirect immunofluorescence assay based on transfected cells and peripheral nerve tissues. After the diagnosis, three patients underwent RCD (rituxima + dexamethasone + cyclophosphamide) chemotherapy. One patient improved (the modified Rankin scale (mRS) score was 3 before treatment and 2 three years after treatment), one patient was stable, and one patient was still in follow-up. One patient was treated with rituxima, and the condition improved (the mRS score was 3 before treatment and 1 one year after treatment). Conclusions MAG-associated peripheral neuropathy can present a slow progressed distal symmetric sensomotor peripheral neuropathy with predominant sensory symptoms. Electromyography shows demyelinating change. Monoclonal protein is usually IgM kappa. MAG-IgM antibodies detection by indirect immunofluorescence assay based on transfected cells and peripheral nerve tissues can support the diagnosis. RCD chemotherapy may be effective.
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The study was designed to establish a 2D UPLC-QTOF method to extrapolate the structure of an unknown substance in carboplatin injection and its relationship with the excipient. By using phenyl-hexyl column (250 mm×4.6 mm, 5 μm) with mobile phase consisting of tetrabutylammonium sulfate buffer (pH 7.5) and acetonitrile in gradient elution mode, an unknown impurity in carboplatin injection was found and quantitatively determined. Then a 2D UPLC-QTOF, HSS T3 column (100 mm×2.1 mm, 1.7 μm) was employed to confirm the molecular weight and the structure of the unknown impurity (electrospray ionization source, positive ion mode, MSE mode) with mobile phase consisting of 0.1% formic acid and acetonitrile. The relationship among impurities, API and excipient was investigated by accelerated stability test with ICP-MS/MS, ICP-AES. Results showed that disodium edetate in the formulation interacted with carboplatin producing an unknown impurity containing platin, and induced the increase of 1,1-cyclobutanedicarboxylic acid. The research should be done on the rationality of the addition of disodium edetate in such injections containing heavy metals.