-
Frontiers in Immunology 2023Rituximab (RTX) is gaining increasing clinical acceptance in the treatment of primary membranous nephropathy (PMN), with demonstrated efficacy and safety. However, there...
BACKGROUND
Rituximab (RTX) is gaining increasing clinical acceptance in the treatment of primary membranous nephropathy (PMN), with demonstrated efficacy and safety. However, there are few clinical studies on RTX for PMN in Asian populations, especially in China.
METHODS
To observe and analyse the efficacy and safety of RTX treatment, 81 patients with PMN suffering from nephrotic syndrome (NS) were enrolled and divided into an initial therapy group, a conventional immunosuppressive therapy relapse group, and a conventional immunosuppressive therapy ineffective group according to their pre-RTX treatment background. Patients in each group were followed up for 12 months. The primary outcome was clinical remission at 12 months, and the secondary outcomes were safety and the occurrence of adverse events.
RESULTS
At 12 months, 65 of 81 (80.2%) patients achieved complete (n=21, 25.9%) or partial (n=44, 54.3%) remission after rituximab treatment. Thirty-two of 36 (88.9%) patients in the initial therapy group, 11 of 12 (91.7%) patients in the relapse group and 22 of 33 (66.7%) patients in the ineffective group achieved clinical remission. All 59 patients with positive anti-PLA2R antibodies showed a decreasing trend in antibody levels after RTX treatment, and 55 (93.2%) of them achieved antibody clearance (<20 U/mL). Logistic regression analysis showed that a high anti-PLA2R antibody titer (OR=0.993, P=0.032) was an independent risk factor for nonremission. Adverse events occurred in 18 (22.2%) patients, of which 5 (6.2%) were serious adverse events, and none were malignant or otherwise fatal.
CONCLUSION
RTX alone can effectively induce remission PMN and maintain stable renal function. It is recommended as the first choice of treatment and is also effective in patients who relapse and have poor responses to conventional immunosuppressive therapy. Anti-PLA2R antibodies can be used as a marker for RTX treatment monitoring, and antibody clearance is necessary to achieve and improve the rates of clinical remission.
Topics: Humans; Rituximab; Retrospective Studies; Glomerulonephritis, Membranous; Neoplasm Recurrence, Local; Immunosuppressive Agents; Antibodies
PubMed: 37187749
DOI: 10.3389/fimmu.2023.1156470 -
Frontiers in Medicine 2023Ustekinumab (UST) optimization strategies, including shortening intervals and intravenous reinduction, should be administered to patients with partial or loss of...
OBJECTIVES
Ustekinumab (UST) optimization strategies, including shortening intervals and intravenous reinduction, should be administered to patients with partial or loss of respond. Evidence comparing these types of optimization treatments is limited. We evaluated the efficacy and safety of weight-based UST intravenous reinduction in patients with refractory Crohn's disease (CD).
METHODS
This was a single-center retrospective observational study. Optimization strategies were designed for patients showing partial or loss of response to standardized UST therapy. Clinical, biochemical, and endoscopic response and remission rate were determined by Crohn's disease activity index (CDAI), C-reactive protein (CRP) levels, and SES-CD evaluation. UST trough concentrations were detected and adverse events were recorded.
RESULTS
A total of 128 patients receiving UST optimization therapies were included, with 105 patients administered shortening intervals of q8w or q4w, and 23 receiving intravenous reinduction followed by subcutaneous q8w or q4w. The follow-up duration for the shortening interval and reinduction cohorts were 15.0 (10.0, 31.0) and 23.0 (13.0, 70.0) weeks, respectively. A significant CDAI delta variation pre-and post-treatment could be found between groups [17.0 (-4.4, 65.9) vs. 69.0(10.7, 151.0), = 0.013]. the trough concentration of UST increased [2.5 (1.3, 5.3) vs. 1.1 (0.5, 2.3), = 0.001] after intravenous reinduction. Clinical and endoscopic remission were achieved in 69.6 and 31.8% of patients in the intravenous reinduction cohort, and 62.9 and 22.2% of patients in the shortening interval cohort, respectively. No significant difference was found between groups regarding safety.
CONCLUSION
Intravenous reinduction brought about favorable recapture of clinical and endoscopic remission, and should have significant priority over the strategy of merely shortening drug intervals, which should be launched before switching to other biologics targeting different inflammatory pathways. identifier NCT04923100. https://classic.clinicaltrials.gov/ct2/show/NCT04923100?id=04923100&draw=2&rank=1.
PubMed: 37554510
DOI: 10.3389/fmed.2023.1105981 -
Boletin Medico Del Hospital Infantil de... 2024Vitiligo is a multifactorial disease characterized by the progressive loss of melanocytes. The worldwide prevalence ranges from 0.5% to 2%, and in children from 0% to...
BACKGROUND
Vitiligo is a multifactorial disease characterized by the progressive loss of melanocytes. The worldwide prevalence ranges from 0.5% to 2%, and in children from 0% to 2.16%. The objective of this study was to determine the variables associated with progression of vitiligo.
METHODS
A retrospective cohort was carried out where a random sample of records of pediatric patients with vitiligo from January 2016 to December 2020 was analyzed. The variables were studied: age at onset, sex, hereditary family history, personal history of thyroid diseases, time of evolution, classification, Köebner phenomena, mucosal vitiligo, halo nevus, premature graying and the presence of other dermatoses. The final state was classified as progression, stability, partial remission and complete remission.
RESULTS
574 children with vitiligo; 290 (50.5%) women, 284 (49.5%) men. Non-segmental vitiligo in 324 (56.4%), segmental vitiligo in 250 (43.6%). Mean age of onset 8.7 years (SD: 4.54). Median evolution time 6 months (25 percentile of 3 months and 75 percentile of 24 months). Family history 27 (4.70%). Thyroid disease 7 (1.21%). Evolution remained stable in 44 (7.7%), 68 (11.8%) had progression, 32 (5.6%) complete remission, 222 (38.7%) partial remission and 208 (36.2%) one consultation. Non-segmental vitiligo was obtained p < 0.028, younger age of onset p < 0.000, and none skin comorbidities p < 0.009.
CONCLUSIONS
The variables that were associated with a more progression were non-segmental vitiligo, early ages at the onset of the disease, and not presenting with other skin diseases.
Topics: Humans; Vitiligo; Male; Female; Retrospective Studies; Child; Prognosis; Child, Preschool; Age of Onset; Adolescent; Disease Progression; Cohort Studies; Infant; Thyroid Diseases
PubMed: 38768496
DOI: 10.24875/BMHIM.23000083 -
Frontiers in Veterinary Science 2021Aortic body tumors, specifically chemodectomas, are the second most common type of canine cardiac tumor; however, information about treatment is currently lacking. This...
Aortic body tumors, specifically chemodectomas, are the second most common type of canine cardiac tumor; however, information about treatment is currently lacking. This study included dogs with a presumptive or definitive diagnosis of an aortic body chemodectoma that underwent treatment with toceranib phosphate. Cases were solicited via the American College of Veterinary Internal Medicine Cardiology, Internal Medicine, and Oncology listservs using an electronic survey. Cox multivariate analysis of factors potentially impacting survival time was completed. Twenty-seven (27) cases were included in analysis. The clinical benefit rate (complete remission, partial remission, or stable disease >10 weeks) was 89%. A median survival time of 478 days was found for those receiving toceranib alone ( = 14), which was not statistically different from those treated with additional modalities (521 days). No factors evaluated statistically impacted outcome. Further, prospective studies are warranted to evaluate the use of toceranib for the treatment of canine aortic body chemodectomas.
PubMed: 33614771
DOI: 10.3389/fvets.2021.635057 -
Frontiers in Endocrinology 2023This long-term study aimed to analyze the associations between BMI -score, HbA1c, and daily insulin requirement (DIR) and the prevalence and duration of partial... (Observational Study)
Observational Study
BACKGROUND/OBJECTIVE
This long-term study aimed to analyze the associations between BMI -score, HbA1c, and daily insulin requirement (DIR) and the prevalence and duration of partial remission (PR) in children and adolescents with type 1 diabetes (T1D).
METHODS
After retrieving retrospective data for 195 patients from their health records at 24, 48, and 72 months after T1D diagnosis, the study group was comprised of 119 (57 girls) children with a complete dataset for all 6 years. PR was defined according to the ISPAD guidelines. Analyses were carried out in the whole group and subgroups according to PR duration: no PR at all (NPR), PR lasting less than 2 years (PR < 2), and PR at least 2 years (PR ≥ 2).
RESULTS
PR was observed in 63% of the patients (78.9% of overweight and 100% of obese patients). NPR patients showed the lowest mean initial BMI -score [-0.65 ± 1.29 vs. 0.02 ± 1.42, (PR < 2), = 0.01 and vs. 0.64 ± 1.43 (PR ≥ 2), = 0.17]. The dissimilarity in BMI across patients declined over time. Within the NPR group, the initial mean BMI -score significantly increased within the first 2 years (unadjusted < 0.001) and remained constant afterward. In the PR <2 group, the highest increase in BMI -score occurred after 4 years ( < 0.001) and then decreased ( = 0.04). In the PR ≥2, the BMI -score slightly decreased within the first 2 years ( = 0.02), then increased ( = 0.03) and remained unchanged for the last 2 years. Six years after T1D started, the mean DIRs do not differ among the patient groups (ANOVA = 0.272).
CONCLUSION
During 6 years of follow-up, PR occurred in almost two-thirds of the studied children including almost all overweight and obese children. We observed a gradual normalization of the BMI -score at the end of the follow-up. BMI -score increased slightly in children with no remission initially but remained later constant until the end of observation. In both remitter groups, the increase in BMI -score appeared later when the protective honeymoon period ended. Regardless of BMI -score, the β-cell destruction process progresses, and after 6 years, the DIR is similar for all patients.
Topics: Adolescent; Female; Humans; Child; Body Mass Index; Diabetes Mellitus, Type 1; Overweight; Pediatric Obesity; Retrospective Studies; Insulin
PubMed: 37780631
DOI: 10.3389/fendo.2023.1257758 -
Glomerular Diseases 2023Minimal change disease and primary FSGS are podocytopathies but are also immune-mediated diseases. Rituximab acts via multiple mechanisms by tilting the balance between... (Review)
Review
BACKGROUND
Minimal change disease and primary FSGS are podocytopathies but are also immune-mediated diseases. Rituximab acts via multiple mechanisms by tilting the balance between autoreactive B and T cells in favor of regulatory B and T cells. The consequences are decreased production of cytokines, chemokines, and permeability factors by these cells. In the past decade, we have seen the discovery of autoantibodies mediating nephrotic syndrome (anti-annexin A2 antibody, anti-UCHL1 antibody, and anti-nephrin antibody), and rituximab decreases their production. Rituximab also binds to podocyte SMPDL3b and has direct podocyte actions.
SUMMARY
Rituximab's role in managing these primary podocytopathies has been discussed in this brief review. Rituximab has been used extensively in children and adults with frequently relapsing and steroid-dependent nephrotic syndrome. However, rituximab is not very promising in adult steroid-resistant nephrotic syndrome. Although ofatumumab would cause prolonged B-cell depletion and is fully humanized, it is unclear if it is superior to rituximab in preventing relapse of nephrotic syndrome.
KEY MESSAGES
Rituximab therapy can induce prolonged remission in adults with frequently relapsing and steroid-dependent nephrotic syndrome. However, no good data exist on using rituximab in steroid-resistant nephrotic syndrome.
PubMed: 37901702
DOI: 10.1159/000533695 -
Pediatric Endocrinology, Diabetes, and... 2021C-peptide, the molecule produced in an equimolar concentration to insulin, has become an established insulin secretion biomarker in diabetic patients. Measurement of... (Review)
Review
C-peptide, the molecule produced in an equimolar concentration to insulin, has become an established insulin secretion biomarker in diabetic patients. Measurement of C-peptide level can be helpful in clinical practice for assessing insulin-producing b-cells residual function, especially in the patients who have already started exogenous insulin therapy. Advances in assays have made measurement of C-peptide more reliable and inexpensive. Traditionally, C-peptide is widely used to differentiate between type 1, type 2 and monogenic types in diabetic patients of all ages, both when the diabetes occurs and even months and years after the initial diagnosis. Moreover, in the patients with type 1 diabetes, the C-peptide secretion can become a reliable predictor of the clinical partial remission in the first months after diagnosis, although noteworthy, its' any specified level is not included in the definition of this phase of the disease. Many other clinical factors such as age, use of innovative technologies, the intensity of physical activity or body mass influence the concentration of C-peptide as well as diabetes remission occurrence and duration. They may interfere the interpretation of C-peptide level in the diabetes course. There is a great need to assess the new, adjusted C-peptide levels in these situations. A multitude novel therapies including immunomodulative factors and stem cell transplants can also use C-peptide in the patient selection and post-therapeutic monitoring of the outcome in researches aimed in extension of remission period. Recent research proves C-peptide presence and preserved function and being the possible important player in better metabolic control in long-lasting diabetes type 1. These findings may open the area for trials to regenerate b-cells and save endogenous insulin secretion for many years after diagnosis. Last but not the least, C-peptide presents its own physiological effect on other tissues, among others on the endothelial function, thus participates in inhibiting micro- and macrovascular diabetes complications. The idea of C-peptide as a new, additional to insulin cure remains as much attractive as elusive.
Topics: Biomarkers; C-Peptide; Child; Diabetes Mellitus, Type 1; Humans; Insulin; Insulin Secretion
PubMed: 34514768
DOI: 10.5114/pedm.2021.107165 -
Balkan Medical Journal Jul 2023Conventional regimens for refractory idiopathic membranous nephropathy (IMN) still have limitations. Rituximab (RTX) has a good effect in the treatment of refractory...
BACKGROUND
Conventional regimens for refractory idiopathic membranous nephropathy (IMN) still have limitations. Rituximab (RTX) has a good effect in the treatment of refractory IMN. However, whether RTX single or combined with immunosuppressive therapy is more effective and whether adverse events will increase are still inconclusive.
AIMS
To investigate the efficacy and safety of RTX combined with low-dose tacrolimus (TAC) versus RTX alone in the treatment of refractory IMN.
STUDY DESIGN
A retrospective cohort study.
METHODS
We retrospectively studied 91 cases of refractory IMN diagnosed between January 2018 and June 2021, all of which immunosuppressive regimens had failed. Thirty-four patients received RTX combined with TAC (RTX + TAC group), and 57 patients were treated with RTX alone (RTX group). The RTX + TAC group was given RTX 1 g once every 2 weeks, two times, and TAC 0.03 mg/kg/day orally. In the RTX group, RTX was given at the same dosage as the RTX + TAC group. Clinical data were collected at 12 months of follow-up to compare the complete and partial remission rates and the incidence of adverse reactions between the two groups.
RESULTS
The overall effectiveness rate of RTX + TAC in the treatment of refractory IMN was 87.14%, of which the partial and complete remission rates were 50.01% and 37.13%, respectively, and the median time to complete remission was 9 (interquartile range [IQR] 6.0, 12.0) months. The overall effectiveness rate of RTX was 65.87%, of which the partial and complete remission rates were 39.48% and 26.39%, respectively, and the median time to complete remission was 10.5 (IQR 6.0, 12.0) months. Adverse events occurred in 6 (17.65%) patients in the RTX + TAC group and in 11 (19.30%) in the RTX group ( = 0.473). Proteinuria and high titer of PLA2R are risk factors for non-remission.
CONCLUSION
The complete and partial remission rates of RTX combined with low-dose TAC in the treatment of refractory IMN are higher than those of RTX alone, and no significant increase in adverse events was noted.
Topics: Humans; Tacrolimus; Glomerulonephritis, Membranous; Rituximab; Retrospective Studies; Drug Therapy, Combination
PubMed: 37260416
DOI: 10.4274/balkanmedj.galenos.2023.2022-9-7 -
World Journal of Clinical Cases Apr 2023Translational therapy refers to a combination of chemotherapy, radiotherapy, targeted therapy, and immunotherapy for patients with advanced gastric cancer who are... (Review)
Review
Translational therapy refers to a combination of chemotherapy, radiotherapy, targeted therapy, and immunotherapy for patients with advanced gastric cancer who are initially unable to undergo R0 resection. This treatment can achieve partial or complete remission of the unresectable tumors to meet the criteria for R0 resection, thus enabling the patients to prolong their survival time and improve their quality of life. In gastric cancer, translational therapy has been tried and improved. At present, there are a large number of patients with locally advanced gastric cancer in China, and the selection of suitable patients for translational therapy to prolong objective survival and improve survival quality is one of the hot spots in the field of gastric cancer research.
PubMed: 37123309
DOI: 10.12998/wjcc.v11.i11.2405 -
Frontiers in Immunology 2020Type 1 diabetes (T1D) is a chronic metabolic disease characterized by the autoimmune destruction of β-cells in the pancreatic islets. T1D is preceded by islet-specific... (Comparative Study)
Comparative Study
Type 1 diabetes (T1D) is a chronic metabolic disease characterized by the autoimmune destruction of β-cells in the pancreatic islets. T1D is preceded by islet-specific inflammation led by several immune cells. Among them, natural killer (NK) cells are emerging as important players in T1D development. Human NK cells are characterized by CD56 and CD16 expression, which allows classifying NK cells into four subsets: 1) CD56CD16 or effector NK cells (NK); 2) CD56CD16 or regulatory NK cells (NK); 3) intermediate CD56CD16 NK cells; and 4) CD56CD16 NK cells, whose function is not well determined. Since many studies have shown that T1D progression is associated with changes in various immune cell types, we hypothesize that the kinetics of NK cell subsets in the blood could correlate with different stages of T1D. To that aim, pediatric patients newly diagnosed with T1D were recruited, and peripheral NK cell subsets were analyzed by flow cytometry at several disease checkpoints: disease onset, partial remission (PR), 8 months (for non-remitters), and 12 months of progression. Our results showed that total NK cells and their four subsets are altered at the early stages of T1D. A decrease in the counts and percentage of total NK cells and NK cells at the different disease stages was found when compared to controls. These results suggest the extravasation of these cells into the islets at disease onset, which is maintained throughout the follow-up. By contrast, NK cells increased during the early stages after T1D onset, and both intermediate NK cells and CD56CD16 NK cells diminished at the PR stage, which might reflect the immunoregulatory attempts and could be candidate biomarkers for this stage. Also, CD56CD16 NK cells increased during T1D progression. Finally, changes in CD16 expression were identified in the different T1D stages, highlighting a CD16 expression reduction in total NK cells and NK cells 1 year after diagnosis. That may reflect a state of exhaustion after multiple cell-to-cell interactions. Altogether, our preliminary data provide a longitudinal picture of peripheral NK cell subpopulations during the different T1D stages, which could be potential candidate biomarkers indicators of disease progression.
Topics: Adolescent; Age Factors; Biomarkers; CD56 Antigen; Case-Control Studies; Child; Child, Preschool; Diabetes Mellitus, Type 1; Disease Progression; Female; Flow Cytometry; GPI-Linked Proteins; Humans; Immunophenotyping; Killer Cells, Natural; Longitudinal Studies; Male; Pancreas; Phenotype; Pilot Projects; Receptors, IgG; Remission Induction; Time Factors; Treatment Outcome
PubMed: 33569058
DOI: 10.3389/fimmu.2020.611522