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1.
J Transl Med ; 22(1): 409, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38693581

ABSTRACT

With the aging global population, type 2 diabetes mellitus (T2DM) and osteoporosis(OP) are becoming increasingly prevalent. Diabetic osteoporosis (DOP) is a metabolic bone disorder characterized by abnormal bone tissue structure and reduced bone strength in patients with diabetes. Studies have revealed a close association among diabetes, increased fracture risk, and disturbances in iron metabolism. This review explores the concept of ferroptosis, a non-apoptotic cell death process dependent on intracellular iron, focusing on its role in DOP. Iron-dependent lipid peroxidation, particularly impacting pancreatic ß-cells, osteoblasts (OBs) and osteoclasts (OCs), contributes to DOP. The intricate interplay between iron dysregulation, which comprises deficiency and overload, and DOP has been discussed, emphasizing how excessive iron accumulation triggers ferroptosis in DOP. This concise overview highlights the need to understand the complex relationship between T2DM and OP, particularly ferroptosis. This review aimed to elucidate the pathogenesis of ferroptosis in DOP and provide a prospective for future research targeting interventions in the field of ferroptosis.


Subject(s)
Diabetes Mellitus, Type 2 , Ferroptosis , Osteoporosis , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Osteoporosis/complications , Osteoporosis/metabolism , Animals , Iron/metabolism
2.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(4): 443-449, 2024 Apr 10.
Article in Chinese | MEDLINE | ID: mdl-38565510

ABSTRACT

OBJECTIVE: To explore the clinical manifestations and genetic basis for a Chinese pedigree affected with atypical Charcot-Marie-Tooth disease type 1 A (CMT1A). METHODS: A patient admitted to the Department of Neurology, Xijing Hospital Affiliated to Air Force Medical University in June 2022 was selected as the study subject. Clinical data of the patient was collected, and 17 family members from four generations of this pedigree were traced based on pes arcuatus and atypical clinical symptoms. Neuroultrasound and genetic testing were carried out on available family members. Whole exome sequencing and multiple ligation-dependent probe amplification assay were carried out for the proband and some of the affected members of the pedigree. RESULTS: The proband, a 15-year-old male, had presented with paroxystic limb pain with weakness, accompanied by pes cavus and hypertrophy of gastrocnemius muscles, without stork leg sign caused by muscles atrophy in the distal lower extremities. MRI has revealed no sign of fat infiltration in the muscles of both legs. Nerve conduction examination had indicated damages of the sensory and motor nerves of the limbs, mainly with demyelinating changes. Seven members of the pedigree had pes arcuatus, including 5 presenting with paroxysmal neuropathic pain and myasthenia in the limbs, whilst 2 were without any clinical symptoms. Neurosonography of the proband, his brother, father and aunt showed thickened peripheral nerves of the extremities with unclear bundle structure. Genetic analysis revealed a large repeat encompassing exons 1 to 5 of the PMP22 gene and flanking regions (chr17: 15133768_15502298) in some of the affected members, which was predicted to be pathogenic. CONCLUSION: The duplication of PMP22 gene was considered to be pathogenic for this CMT1A pedigree.


Subject(s)
Charcot-Marie-Tooth Disease , Male , Humans , Adolescent , Charcot-Marie-Tooth Disease/genetics , Charcot-Marie-Tooth Disease/pathology , Pedigree , Myelin Proteins/genetics , Muscle, Skeletal , China , Gene Duplication
3.
QJM ; 117(2): 109-118, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-37802883

ABSTRACT

BACKGROUND: The environmental effects on the prognosis of ocular myasthenia gravis (OMG) remain largely unexplored. AIM: To investigate the association between specific environmental factors and the generalization of OMG. DESIGN: The cohort study was conducted in China based on a nationwide multicenter database. METHODS: Adult patients with OMG at onset, who were followed up for at least 2 years until May 2022, were included. We collected data on demographic and clinical factors, as well as environmental factors, including latitude, socioeconomic status (per capita disposable income [PDI] at provincial level and education) and smoking. The study outcome was the time to the development of generalized myasthenia gravis (GMG). Cox models were employed to examine the association between environmental exposures and generalization. Restricted cubic spline was used to model the association of latitude with generalization risk. RESULTS: A total of 1396 participants were included. During a median follow-up of 5.15 (interquartile range [IQR] 3.37-9.03) years, 735 patients developed GMG within a median of 5.69 (IQR 1.10-15.66) years. Latitude of 20-50°N showed a U-shaped relation with generalization risk, with the lowest risk at around 30°N; both higher and lower latitudes were associated with the increased risk (P for non-linearity <0.001). Living in areas with lower PDI had 1.28-2.11 times higher risk of generalization. No significant association was observed with education or smoking. CONCLUSIONS: Latitude and provincial-level PDI were associated with the generalization of OMG in China. Further studies are warranted to validate our findings and investigate their potential applications in clinical practice and health policy.


Subject(s)
Myasthenia Gravis , Adult , Humans , Cohort Studies , Disease Progression , Myasthenia Gravis/epidemiology , Myasthenia Gravis/complications , Prognosis , Retrospective Studies
4.
Heliyon ; 9(9): e20041, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37809435

ABSTRACT

A common spinal condition known as lumbar disc herniation (LDH) can result in radicular and low back discomfort. A 27-year-old man was admitted to our hospital with a 6-year history of persistent low back pain, and his low back pain had recurred with radiation to his lower extremities over the last two months. An extensive right-sided paracentral disc herniation in the L5/S1 intervertebral region, which compressed the nerve root, was discovered by magnetic resonance imaging (MRI) of his lumbar spine. After receiving conservative treatment, the patient reported that his lower back discomfort and neurogenic claudication had gradually subsided after 4 months. After one year, a follow-up MRI showed that the massive, prolapsed disc herniation at the L5/S1 level had totally disappeared. The sagittal protrusion length of the L5/S1 intervertebral disc shrank from 12.35 mm to 3.49 mm. However, there remained a chance of vertebral height loss. During the course of treatment, the height of the L5/S1 intervertebral space was still slightly reduced. The intervertebral space height declined from 7.705 mm to 7.201 mm after one year of treatment. The current case and a review of the literature demonstrate that LDH can decrease with conservative therapy over a short period of time. We stress the effectiveness of conservative treatment in very select LDH cases that lack a clear surgical justification.

5.
J Orthop Surg Res ; 18(1): 632, 2023 Aug 28.
Article in English | MEDLINE | ID: mdl-37641046

ABSTRACT

PURPOSE: The ideal approach for revision surgery following femoral head salvage treatments for an intertrochanteric fracture is still up for debate. A novel variety of proximal femoral bionic intramedullary nail (PFBN) has been created in clinical practice. We aimed to compare the biomechanical results of the novel implant to conventional intramedullary and extramedullary fixation in the treatment of intertrochanteric fracture following primary internal fixation failure. METHODS: Using finite element analysis, we created a three-dimensional model of the intertrochanteric fracture's helical blade cut-out for this investigation. The PFBN 1 group, the PFBN 2 group, the PFNA group, and the DHS group were our four test groups. For each fracture group, the von Mises stress and displacements of the femur and internal fixation components were measured under 2100 N axial loads. RESULTS: The values for the femoral displacement in the PFBN1 group, PFBN2 group, PFNA group, and DHS group were 6.802 mm, 6.716 mm, 8.080 mm, and 8.679 mm, respectively. The internal implant displacement values were 6.201 mm, 6.138 mm, 7.396 mm, and 8.075 mm in the PFBN1 group, PFBN2 group, PFNA group, and DHS group, respectively. The maximum von Mises Stress in the femoral was 187.2 MPa, 85.18 MPa, 106.6 MPa, and 386.2 MPa in the PFBN1 groups, PFBN2 groups, PFNA groups, and DHS groups, respectively. In the PFBN1 groups, PFBN2 groups, PFNA groups, and DHS groups, the maximum von Mises Stress in internal fixation was 586.7 MPa, 559.8 MPa, 370.7 MPa, and 928.4.8 MPa, respectively. CONCLUSION: Our biomechanical research demonstrates that intramedullary fixation is more stable than extramedullary fixation when salvaging failed internal fixations in intertrochanteric fracture. Compared with PFNA and DHS, PFBN showed better biomechanical stability in the treatment of patients with revised intertrochanteric fractures. In light of this, we advocate PFBN fixation as the method of choice for intertrochanteric fracture revision. This result still has to be confirmed in more clinical research.


Subject(s)
Fracture Fixation, Internal , Hip Fractures , Humans , Internal Fixators , Hip Fractures/surgery , Bionics , Femur
6.
Ann Clin Transl Neurol ; 10(4): 589-598, 2023 04.
Article in English | MEDLINE | ID: mdl-36808840

ABSTRACT

OBJECTIVE: Use of tacrolimus in mild to moderate myasthenia gravis (MG) is generally limited to glucocorticoid-refractory cases; the advantage of mono-tacrolimus over mono-glucocorticoids is unknown. METHODS: We included mild to moderate MG patients treated with mono-tacrolimus (mono-TAC) or mono-glucocorticoids (mono-GC). The correlation between the immunotherapy options and the treatment efficacy and side effects were examined in 1:1 propensity-score matching. The main outcome was time to minimal manifestations status or better (MMS or better). Secondary outcomes include time to relapse, the mean changes in Myasthenia Gravis-specific Activities of Daily Living (MG-ADL) scores and the rate of adverse events. RESULTS: Baseline characteristics showed no difference between matched groups (49 matched pairs). There were no differences in median time to MMS or better between the mono-TAC group and mono-GC group (5.1 vs. 2.8 months: unadjusted hazard ratio [HR], 0.73; 95% CI, 0.46-1.16; p = 0.180), as well as in median time to relapse (data unavailable for the mono-TAC group since 44 of 49 [89.8%] participants remained in MMS or better; 39.7 months in mono-GC group: unadjusted HR, 0.67; 95% CI, 0.23-1.97; p = 0.464). Changes in MG-ADL scores between the two groups were similar (mean differences, 0.3; 95% CI, -0.4 to 1.0; p = 0.462). The rate of adverse events was lower in the mono-TAC group compared to the mono-GC group (24.5% vs. 55.1%, p = 0.002). INTERPRETATION: Mono-tacrolimus performs superior tolerability with non-inferior efficacy compared to mono-glucocorticoids in mild to moderate myasthenia gravis patients who refuse or have a contraindication to glucocorticoids.


Subject(s)
Myasthenia Gravis , Tacrolimus , Humans , Tacrolimus/adverse effects , Glucocorticoids/adverse effects , Activities of Daily Living , Neoplasm Recurrence, Local/chemically induced , Neoplasm Recurrence, Local/drug therapy , Myasthenia Gravis/drug therapy , Chronic Disease
8.
BMC Musculoskelet Disord ; 24(1): 54, 2023 Jan 21.
Article in English | MEDLINE | ID: mdl-36681804

ABSTRACT

BACKGROUND: A consensus regarding the optimal approach for treating femoral neck fractures is lacking. We aimed to investigate the biomechanical outcomes of Femoral Neck System (FNS) internal fixation components in the treatment of nonanatomically reduced femoral neck fractures. METHOD: We constructed two types of femoral neck fractures of the Pauwels classification with angles of 30° and 50°, and three models of anatomic reduction, positive buttress reduction and negative buttress reduction were constructed. Subgroups of 1 to 4 mm were divided according to the distance of displacement in the positive buttress reduction and negative buttress reduction models. The von Mises stress and displacements of the femur and FNS internal fixation components were measured for each fracture group under 2100-N axial loads. RESULTS: When the Pauwels angle was 30°, the positive 1-mm and 2-mm models had lower FNS stress than the negative buttress model. The positive 3- and 4-mm models showed FNS stress similar to that of the negative buttress model. But the four positive buttress models had similar stresses on the femur as the negative buttress model. When the Pauwels angle was 50°, the four positive buttress models had higher FNS stress than the negative buttress model. Three positive buttress models (2 mm, 3 and 4 mm) resulted in lower stress of the femur than the negative buttress model, though the 1-mm model did not. When the Pauwels angle was 30°, the positive buttress model had a lower displacement of the FNS than the negative buttress model and a similar displacement of the femur with the negative buttress model. When the Pauwels angle was 50°, the positive buttress model had a higher displacement of the FNS and femur than the negative buttress model. Our study also showed that the von Mises stress and displacement of the internal fixation and the femur increased as the fracture angle increased. CONCLUSION: From the perspective of biomechanics, when the Pauwels angle was 30°, positive buttress was more stable to negative buttress. However, when the Pauwels angle was 50°, this advantage weakens. In our opinion, the clinical efficacy of FNS internal fixation with positive buttress may be related to the fracture angle, neck-shaft angle and alignment in the lateral view. This result needs verification in further clinical studies.


Subject(s)
Femoral Neck Fractures , Femur Neck , Humans , Femur Neck/diagnostic imaging , Femur Neck/surgery , Finite Element Analysis , Femoral Neck Fractures/diagnostic imaging , Femoral Neck Fractures/surgery , Treatment Outcome , Fracture Fixation, Internal/methods , Biomechanical Phenomena
9.
Injury ; 53(8): 2754-2762, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35760641

ABSTRACT

BACKGROUND: Consensus regarding the optimal amount of bone cement and vertebral height in the treatment of osteoporotic vertebral compression fractures (OVCFs) is lacking. Our purpose was to explore the optimal amount of bone cement and vertebral height in OVCF after percutaneous vertebral augmentation (PVA). METHODS: A three-dimensional finite element model of the L1-L3 segments was constructed from CT scans of aging osteoporosis patients. Four different postoperative vertebral height models were simulated according to Genant semiquantitative grades 0, 1, 2, and 3. The volume of bone cement filling ranged from 3 ml to 6 ml. These models evaluated the von Mises stress of injured vertebral bodies, adjacent vertebral bodies and intervertebral discs under flexion, extension, left flexion, and right flexion after PVA. RESULTS: When the bone cement content was held constant, as the height of the vertebral body decreased, the stress of the L2 vertebral body decreased during left flexion and right flexion, but the stress of the L2 vertebral body increased and decreased during flexion and extension. As the height of the vertebral body decreased, the stress of the L1-L2 intervertebral disc increased. There was no significant change in the stress of other adjacent vertebrae or intervertebral discs. When the Genant grade was 0, 1, or 2 (3 ml and 4 ml), the stress of the overall vertebral body was closest to normal. CONCLUSIONS: When the height of the vertebral body is restored to the same height, a bone cement filling volume of 3 ml to 6 ml is suitable and will not produce a significant change in the stress of the vertebral body or adjacent vertebral body. As vertebral body height was lost, it may promote the degeneration of the intervertebral disc above the injury vertebrae after PVA. It is appropriate for the height of the vertebral body to return to Genant grade 0 or Genant grade 1 after surgery. When the height of the vertebral body has Genant grade 2 status, it was best to use 3 ml to 4 ml of bone cement filling. Therefore, when treating OVCFs, clinicians do not need to pursue complete reduction of the vertebral body. It is also important to verify the biomechanics results in clinical studies.


Subject(s)
Fractures, Compression , Osteoporotic Fractures , Spinal Fractures , Bone Cements/therapeutic use , Finite Element Analysis , Fractures, Compression/diagnostic imaging , Fractures, Compression/surgery , Humans , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/injuries , Lumbar Vertebrae/surgery , Osteoporotic Fractures/diagnostic imaging , Osteoporotic Fractures/drug therapy , Osteoporotic Fractures/surgery , Spinal Fractures/diagnostic imaging , Spinal Fractures/surgery
10.
Front Neurol ; 13: 816243, 2022.
Article in English | MEDLINE | ID: mdl-35185767

ABSTRACT

OBJECTIVE: Despite the high efficiency of glucocorticoids (GCs), ~18-34% patients with myasthenia gravis (MG) may experience relapses of the disease. Here, we aim to identify clinical factors related to relapses during steroid tapering or after withdrawal in MG patients who were well-managed on steroid monotherapy. METHODS: We conducted a retrospective study on 125 MG patients from the Xuanwu Hospital MG Trial Database. Patients were treated with corticosteroids and achieved minimal manifestation status (MMS) or better. Patients were divided into steroid reduction subset (N = 74) and steroid withdrawal subset (N = 51). Clinical characteristics and therapeutic data were compared between patients with disease relapse and those who maintained clinical remission at the last follow-ups. Cox proportional hazards regression models were used to identify risk factors of relapse in each subset. RESULTS: Thirty-seven (29.6%) patients experienced relapses during the follow-up periods. Relapse during the steroid reduction was significantly associated with drug reducing duration (HR = 0.81, 95%CI 0.74-0.89, P < 0.001). Risk of relapse was augmented if the drug reducing duration was <11.5 months (HR 27.80, 95%CI 5.88-131.57, P < 0.001). Among patients who discontinued the steroids, those with onset symptoms of bulbar weakness (adjusted HR 3.59, 95%CI 1.19-10.81, P = 0.023) were more likely to experience relapse. CONCLUSION: Our study demonstrated that patients could benefit from prolonged steroid-reducing duration to prevent disease relapse. Patients with bulbar weakness at disease onset should be proposed to take long-term steroids or other immunosuppressants.

11.
J Neuroophthalmol ; 42(1): e260-e266, 2022 03 01.
Article in English | MEDLINE | ID: mdl-34369469

ABSTRACT

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder involving neuromuscular junctions and more than half of MG patients manifested with extraocular muscle weakness initially. In the remained patients, ocular weakness may occur later in the course of the disease. However, little data are available about ocular involvement in such patients. Therefore, the study aims to investigate ocular weakness in MG patients with nonocular onset and evaluate the associated factors influencing it. METHODS: In our monocentric retrospective study, 54 adult-onset patients with MG with nonocular onset were included and were followed up for at least 2 years from the onset. The primary outcome was the occurrence of ptosis, diplopia, or both. Kaplan-Meier analysis was performed to estimate the time to the ocular weakness, and log-rank tests were used to analyze the association between clinical characteristics and ocular weakness. Multivariate Cox proportional hazards regression models were used to identify factors associated with ocular involvement. RESULTS: A total of 47 (87.0%) patients developed ocular weakness during the study period. The median time to ocular weakness was 6.0 months. Time to the ocular involvement was earlier in patients with bulbar onset (P = 0.007), whereas patients receiving pyridostigmine monotherapy and immunomodulatory therapy had a longer median time of ocular weakness (P < 0.0001). No significant difference was noted between ocular weakness and age of onset, gender, and thymoma. The Cox analysis showed that bulbar onset was a risk factor of ocular weakness (adjusted hazard ratio [HR] 2.65, 95% confidence interval [CI] 1.41-4.99), whereas pyridostigmine monotherapy (adjusted HR 0.28, 95% CI 0.13-0.60) and immunotherapy (adjusted HR 0.09, 95% CI 0.04-0.22) were protective factors. CONCLUSIONS: Eighty-seven percent of patients with MG with nonocular onset developed ocular weakness. Bulbar onset was an independent risk factor for ocular involvement, whereas pyridostigmine and immunotherapy were protective factors.


Subject(s)
Blepharoptosis , Myasthenia Gravis , Adult , Blepharoptosis/complications , Blepharoptosis/etiology , Humans , Muscles , Myasthenia Gravis/complications , Myasthenia Gravis/diagnosis , Myasthenia Gravis/drug therapy , Pyridostigmine Bromide/therapeutic use , Retrospective Studies
12.
Front Neurol ; 12: 766942, 2021.
Article in English | MEDLINE | ID: mdl-34867752

ABSTRACT

Background: Selenoprotein N-related myopathies (SEPN1-RMs) are a subset of congenital myopathies caused by mutations of Selenoprotein N gene (SELENON or SEPN1). Clinical phenotype is considered as highly consistent and little attention has been given to the extramuscular abnormalities. Methods: We reported clinical, histopathological, and genetic features of four Chinese patients with SEPN1-RM and performed literature review on delayed respiratory insufficiency and extramuscular involvement. Results: A total of four patients exhibited both the typical and atypical clinical features of SEPN1-RM. The classical manifestations included axial and limb girdle weakness, spinal rigidity, scoliosis, respiratory insufficiency, and multiminicore morphological lesions. However, high interindividual variability was noticed on disease severity, especially the onset of respiratory involvement. Two adult patients postponed respiratory insufficiency to the third decade of life, while two juvenile patients manifested early hypoventilation with puberty exacerbation. As atypical features, extramuscular involvement of weight gain, subcutaneous adipose tissue accumulation, intellectual disability, and mild cardiac changes were observed. Molecular findings revealed three novel mutations of SELENON such as c.1286_1288 del CCT, c.1078_1086dupGGCTACATA, and c.785 G>C. Ten cases with delayed respiratory insufficiency were identified from previous publications. A total of 18 studies described extramuscular abnormalities including joint contractures, alterations of body mass index (BMI), mild cardiac changes, and insulin resistance. Intellectual impairment was extremely rare. Conclusion: SEPN1-RM should be considered as a differential diagnosis in adult patients with delayed respiratory involvement. Extramuscular involvement such as body composition alterations deserves more clinical attention. The novel mutations of SELENON widened the genetic spectrum of patients with SEPN1-RM.

13.
Injury ; 52(8): 2116-2125, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34154816

ABSTRACT

BACKGROUND: Consensus regarding the optimal approach for the treatment of femoral neck fractures remains lacking. A new internal fixation femoral neck system (FNS) was developed and used in clinical practice. We aimed to investigate the biomechanical outcomes of different types of FNS in the treatment of unstable femoral neck fractures. METHOD: In this study, we constructed three different types of unstable femoral neck fractures of Pauwels classification with angles of 50°, 60°, and 70°. We set up four test groups, namely, the one-hole plated FNS group, two-hole plated FNS group, inverted cannulated screw group and triangle cannulated screw group. Under 2100 N axial loads, displacements and the von Mises stress of the femur and internal fixation components were measured for each fracture group. RESULTS: When the Pauwels angle was 50°or 60°, the one-hole locking plated FNS was as superior as the two-hole plated FNS in terms of femur and internal fixation displacement, and the inverted cannulated screw had slightly better stability than the triangular cannulated screw. However, when the angle increases to 70°, the two-hole locking plate has the minimum displacement, followed by the triangular cannulated screw and inverted cannulated screw, which is the worst displacement for the single-hole locking plate. Regardless of the angle, the two sets of FNS have higher internal fixation stress than the two sets of cannulated screws, which is approximately 1.6-3.0 times that of the cannulated screw group. CONCLUSION: From the perspective of biomechanics, we suggest that when the angle of the fracture line is less than 60°, both single-hole locking plated or double-hole locking plated FNS can be used to treat unstable femoral neck fractures. However, when the angle of the fracture line is greater than 70°, we recommend using a double-hole locking plated FNS. This result needs further verification in further clinical studies.


Subject(s)
Femoral Neck Fractures , Biomechanical Phenomena , Bone Screws , Femoral Neck Fractures/diagnostic imaging , Femoral Neck Fractures/surgery , Femur Neck , Finite Element Analysis , Fracture Fixation, Internal , Humans
14.
J Neuroimmunol ; 355: 577571, 2021 06 15.
Article in English | MEDLINE | ID: mdl-33866281

ABSTRACT

The study aims to identify clinical factors affecting tacrolimus blood trough concentration (C0) in myasthenia gravis (MG) patients and to optimize the initial dose of tacrolimus in MG treatment. A total of 103 MG patients participated in this study, and their clinical factors, medication regimens, C0 values and CYP3A5*3 polymorphisms were collected in detail. We used a linear mixed model to analyze the effect of multiple factors on the dosage-weighted C0 (C0:D) and performed subgroup analyses to investigate the consistency of correlations between influencing factors and the C0:D ratios. Among all factors, CYP3A5*3 polymorphism and age showed a strong positive correlation with C0:D ratios. The C0:D ratios (ng/ml·mg-1) were higher for CYP3A5*3/*3 than for CYP3A5*1 (mean difference: 1.038, 95% confidence interval [CI]: 0.820-1.256, P-value <0.001), and for age in the range of 45-64 and ≥ 65 years than for age < 45 years (mean difference [95% CI] and P-value: 0.531[0.257-0.805] and P-value <0.001, 0.703 [0.377-1.029] and P-value <0.001, respectively). The C0:D ratios were not related to corticosteroid dosage, body weight, sex, hematocrit or the concomitant use of calcium channel blockers. The consistencies of the correlations between C0:D ratios and CYP3A5*3 polymorphism or age were confirmed by subgroup analyses. Thus, CYP3A5*3 polymorphism and age should be considered in optimizing the initial dose of tacrolimus for MG treatment.


Subject(s)
Cytochrome P-450 CYP3A/genetics , Immunosuppressive Agents/blood , Myasthenia Gravis/blood , Myasthenia Gravis/genetics , Polymorphism, Genetic/genetics , Tacrolimus/blood , Adult , Age Factors , Aged , Drug Monitoring/methods , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Myasthenia Gravis/drug therapy , Tacrolimus/therapeutic use
15.
Ther Adv Neurol Disord ; 14: 1756286420986747, 2021.
Article in English | MEDLINE | ID: mdl-33552238

ABSTRACT

BACKGROUND: Intravenous immunoglobulin (IVIG) has been commonly used to treat myasthenia gravis exacerbation, but is still ineffective in nearly 30% of patients. A variable number of tandem repeat (VNTR) polymorphism in the FCGRT gene has been found to reduce the efficiency of IgG biologics. However, whether the polymorphism influences the efficacy of IVIG in generalized myasthenia gravis (MG) patients with exacerbations remains unknown. METHODS: The distribution of VNTR genotypes was analyzed in 334 patients with MG. Varied VNTR alleles were determined by capillary electrophoresis and confirmed by Sanger sequencing. Information of endogenous IgG levels were collected in patients without previous immunotherapy (n = 26). Medical records of patients who received IVIG therapy were retrospectively analyzed for therapeutic outcomes of IVIG treatment (n = 61). Patients whose Activities of Daily Living scores decreased by 2 or more points on day 14 were considered responders to the treatment. RESULTS: The VNTR3/3 and VNTR2/3 genotypes were detected in 96.7% (323/334) and 3.4% (11/334) patients, respectively. Patients with VNTR2/3 heterozygosity had lower endogenous IgG levels than those with VNTR3/3 homozygosity (9.81 ± 2.61 g/L versus 12.41 ± 2.45g/L, p = 0.016). The response rate of IVIG therapy was 78.7% (48/61). All responders and nine non-responders were VNTR3/3 homozygotes, whereas all the patients with VNTR2/3 genotypes were non-responders (n = 4). In patients who took IVIG treatments, endogenous IgG levels were significantly lower in non-responders compared with responders (12.93 ± 2.24 g/L versus 8.85 ± 2.69 g/L, p = 0.006), especially in VNTR2/3 heterozygotes (7.86 ± 1.78 g/L, p = 0.001). CONCLUSION: The VNTR2/3 genotype could influence endogenous IgG levels and serve as a predictive marker for poor responses to IVIG in MG patients.

16.
Front Neurol ; 11: 594152, 2020.
Article in English | MEDLINE | ID: mdl-33193063

ABSTRACT

Background and Purpose: Tacrolimus (TAC) has been proven to be a rapid-acting, steroid-sparing agent for myasthenia gravis (MG) therapy. However, evidence related to the effectiveness of TAC alone is rare. Therefore, this study was performed to investigate the effect of TAC monotherapy in MG patients. Methods: Forty-four MG patients who received TAC monotherapy were retrospectively analyzed. A mixed effect model was used to analyze improvements in MG-specific activities of daily living scale (MG-ADL), quantitative MG score (QMG) and MG-ADL subscores. Kaplan-Meier analysis was used to estimate the cumulative probability of minimal manifestations (MM) or better. Adverse events (AEs) were recorded for safety analyses. Results: Of the patients receiving TAC monotherapy, MG-ADL scores were remarkably improved at 3, 6 and 12 months compared with scores at baseline (mean difference and 95% CIs: -3.29 [-4.94, -1.64], -3.97 [-5.67, -2.27], and -4.67 [-6.48, -2.85], respectively). QMG scores significantly decreased at 6 and 12 months, with mean differences and 95% CIs of -4.67(-6.88, -2.45) and -5.77 (-7.55, -4.00), respectively. Estimated median period to achieve "MM or better" was 5.0 (95% CIs, 2.8, 7.2) months. Ocular MG (OMG) and generalized MG (GMG) showed similar therapeutic effects in cumulative probabilities of "MM or better" (P-value = 0.764). A better response was observed in MG-ADL subscores for ptosis and bulbar symptoms. AEs occurred in 37.5% of patients and were generally mild and reversible. Conclusions: TAC monotherapy is a promising option to rapidly alleviate all symptoms of MG, especially for ptosis and bulbar symptoms.

17.
Zhongguo Gu Shang ; 33(6): 576-84, 2020 Jun 25.
Article in Chinese | MEDLINE | ID: mdl-32573167

ABSTRACT

OBJECTIVE: To systematically assess the efficacy of anterior cervical corpectomy and fusion (ACCF) versus posterior laminoplasty (LAMP) for cervical ossification of posterior longitudinal ligament (OPLL). METHODS: PubMed and EMBASE, Cochrane Library, CBM, CNKI, Wanfang and VIP were collected from 7 databases of ACCF, LAMP from 1970 to May 2018. According to the criteria, the articles were included and independently screened by two authors. The quality of the articles was assessed by using the MINORS scale (methodological index for non randomized studies). After extracting the data from the article, the JOA score, cervical curvature, operation time, bleeding volume, excellent and good rate, recovery rate, adverse events and secondary surgery were analyzed by using Review Manager 5.3 software. RESULTS: Finally, a total of 22 articles with 1 678 patients were included in this Meta-analysis, with 810 patients in ACCF group and 868 patients in LAMP group. Meta analysis results showed that the ACCF group had higher postoperative JOA scores[MD=0.63, 95%CI(0.05, 1.20), P= 0.03], higher excellent rate [OR=1.85, 95%CI (1.14, 3.02), P=0.01] and higher recovery rate [OR=11.90, 95%CI (5.75, 18.05), P=0.000 1]. But the LAMP group has a shorter operative time [MD=52.19, 95%CI (29.36, 75.03), P<0.000 01], less complications [OR=1.56, 95%CI (1.03, 2.35), P=0.04] and less reoperations [OR=3.73, 95%CI (1.62, 8.57), P=0.002]. There was no significant different in postoperative lordosis [MD=3.15, 95%CI(-0.14, 6.43), P=0.06] and blood loss[SMD= 0.26, 95%CI(-0.05, 0.57), P=0.10] between two groups. CONCLUSION: The recovery of functionof ACCF group was better, but operation time, complications and reoperations of LAMP group were all better than ACCF group. There was no difference in postoperative lordosis and intraoperative blood loss between two groups. However, there are some limitations in this study. Therefore, higher quality and larger sample size clinical studies are needed to further verify.


Subject(s)
Laminoplasty , Ossification of Posterior Longitudinal Ligament , Spinal Fusion , Vertebroplasty , Calcium , Cervical Vertebrae , Decompression, Surgical , Humans , Treatment Outcome
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 12(2): 170-3, 2004 Apr.
Article in Chinese | MEDLINE | ID: mdl-15157327

ABSTRACT

To investigate the hematological abnormality and clinical characteristics in systemic lupus erythematosus (SLE), the hematological data of 58 SLE and the curative effects of corticosteroid and immunosuppressive agents on SLE were retrospectively analysed by using SPSS/PC software. The results showed that the incidence of hematological abnormalities in 58 cases was as follows: 50 cases of hemogram abnormality (86.2%), 41 of anemia (70.7%), 34 of thrombocytopenia (58.7%), 37 of leukopenia (63.8%). Peripheral cytopenia of every cell lineage was common in SLE. The cell abnormalities of two or three lineages were seen in 41 cases (70.7%). The initial symptoms with hematological abnormality were found in 12 cases (20.7%), 7 out of 12 cases were erroneously diagnosed as hematology diseases (12.1%). In 30 out of 58 patients, the results of bone marrow examination showed that 23 had hyperplasia (76.7%) and 7 were hypoplasia. In 25 out of 38 cases, splenomegaly (65.8%) was found by B ultrasonography. In 25 patients with SLE receiving Coombs test, 3 were positive (12.0%). PAIg increased in 16 out of 22 cases of thrombocytopenia (72.7%). 26 cases of SLE with two or three lineage cytopenia in peripheral blood were treated by corticosteroid and immunosuppressive agent. The hemogram improved in all patients including 6 cases of bone marrow hypoplasia. It is concluded that the hematological abnormalities are frequent in SLE patients, which are short of specialty. The cytopenia of two or more lineage in peripheral blood is most common when bone marrow shows hyperplastic. The therapy with corticosteroid and immunosuppressive agents is efficacious.


Subject(s)
Hematologic Diseases/etiology , Lupus Erythematosus, Systemic/complications , Adolescent , Adult , Aged , Bone Marrow Examination , Child , Female , Humans , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/therapy , Male , Middle Aged
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