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Clinicopathological features and outcome in elderly patients with idiopathic membranous nephropathy.Renal Failure Dec 2023Idiopathic membranous nephropathy (IMN) is the leading cause of nephrotic syndrome in the elderly. The treatment of idiopathic membranous nephropathy is quite...
BACKGROUND
Idiopathic membranous nephropathy (IMN) is the leading cause of nephrotic syndrome in the elderly. The treatment of idiopathic membranous nephropathy is quite challenging due to the particularity of elderly patients. This study intends to investigate the clinicopathological characteristics and initial therapeutic effect of idiopathic membranous nephropathy among elderly patients.
METHODS
A retrospective study of 67 elderly patients (58.2% male, median age 69.0 years, range, 65-83 years) with biopsy-proven membranous nephropathy was conducted at Guangdong Provincial People's Hospital from 2016 to 2020. Data on clinicopathological characteristics and initial therapeutic effects were analyzed.
RESULTS
Of the 67 patients, the mean eGFR of overall patients was 66.49 mL/min/1.73m while the median urine protein-to-creatinine ratio (uPCR) and urine albumin-to-creatinine ratio (uACR) was 5676.73 mg/g and 2951.56 mg/g, respectively. Pathological data revealed that the membranous Churg's stage II was the most frequent (71.64%). Moreover, glomerular PLA2R antigen fluorescence intensity of (+) and IgG4 antigen fluorescence intensity of (++) were detected in 63.6% and 86.4% of all patients, respectively. Overall, 44 patients, accounting for 65.7%, achieved remission including complete remission and partial remission within 1 year after renal biopsy. Compared with a non-remission group, the levels of uPCR (6274.6 vs. 3235.6 mg/g, = 0.007) and uACR (3433.6 vs. 1773.2 mg/g, = 0.017) were significantly higher in remission group. The proportion of immunosuppressive therapy in the remission group was also higher (86.4% vs. 30.4%, < 0.01). Compared with conservative treatment, patients with combined treatment with glucocorticoid and cyclophosphamide (CTX) or glucocorticoid and calcineurin inhibitor (CNIs) achieved higher remission rate (glucocorticoid plus cyclophosphamide vs. conservative treatment, 84.6% vs. 27.3%, = 0.001; glucocorticoid plus calcineurin inhibitor vs. conservative treatment, 88.0% vs. 27.3%, < 0.001). Further analysis showed that compared with patients who underwent conservative treatment, the proportion of males, the levels of uPCR, uACR, BUN, Scr, CysC and PLA2R antigen-positive staining rate in kidney biopsy were higher in those who underwent combined treatment with glucocorticoid and CTX, while the levels of eGFR, TP and ALB were lower ( < 0.05). In addition, patients who received combined treatment with glucocorticoid and CNIs had higher levels of uPCR, uACR, TC and lower levels of TP, ALB than those who received conservative treatment ( < 0.05). Moreover, there were no statistically significant differences in the 1-year progression rate in eGFR between the immunosuppressive treatment group and conservative treatment group (3.3 vs. 0.2 ml/min/1.73m, = 0.852).
CONCLUSIONS
Most elderly patients diagnosed with IMN had multiple comorbidities, and the membranous Churg's stage II was most common. The glomerular PLA2R and IgG4 antigen deposition were frequently detected accompanied by glomerulosclerosis and severe tubulointerstitial injury. For high-risk elderly patients with severe proteinuria, early initial immunosuppressive therapy could achieve a higher urinary protein remission rate. Therefore, it is crucial for clinicians to balance the risks and benefits of immunosuppressive therapy based on clinical and pathological characteristics and develop individualized treatment regimens for elderly patients with IMN.
Topics: Humans; Male; Aged; Female; Glomerulonephritis, Membranous; Retrospective Studies; Glucocorticoids; Calcineurin Inhibitors; Creatinine; Immunosuppressive Agents; Cyclophosphamide; Immunoglobulin G
PubMed: 37194712
DOI: 10.1080/0886022X.2023.2212081 -
Blood Cancer Journal Mar 2024The objective of our study was to report real-world data on the safety and efficacy of standard-of-care teclistamab in patients with relapsed/refractory multiple myeloma...
The objective of our study was to report real-world data on the safety and efficacy of standard-of-care teclistamab in patients with relapsed/refractory multiple myeloma (MM). This is a multi-institutional retrospective cohort study and included all consecutive patients that received at least one dose of teclistamab up until August 2023. One hundred and ten patients were included, of whom, 86% had triple-class refractory disease, 76% penta-refractory disease, and 35% had prior exposure to B-cell maturation antigen (BCMA)-targeting therapies. The overall response rate (ORR) in our cohort was 62%, with a ≥ very good partial remission (VGPR) rate of 51%. The ORR in patients with and without prior BCMA-targeted therapies was 54% vs 67%, respectively (p = 0.23). At a median follow-up of 3.5 months (range, 0.39-10.92), the estimated 3 month and 6 month progression free survival (PFS) was 57% (95% CI, 48%, 68%) and 52% (95% CI, 42%, 64%) respectively. The incidence of cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) was 56% and 11% respectively, with grade ≥3 CRS and ICANS noted in 3.5% and 4.6% of patients respectively. 78 unique infections were diagnosed in 44 patients, with the incidence of all-grade and grade ≥3 infections being 40% vs 26% respectively. Primary prophylaxis with intravenous immunoglobulin (IVIG) was associated with a significantly lower infection risk on multivariate analysis (Hazard ratio [HR] 0.33; 95% CI 0.17, 0.64; p = 0.001).
Topics: Humans; Multiple Myeloma; B-Cell Maturation Antigen; Retrospective Studies; Neoplasms, Plasma Cell; Antibodies, Bispecific; Antineoplastic Agents; Pentaerythritol Tetranitrate
PubMed: 38443345
DOI: 10.1038/s41408-024-01003-z -
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 -
Signal Transduction and Targeted Therapy Sep 2023Anti-programmed cell death-1 (anti-PD-1) therapies have shown a favorable efficacy and good tolerance for relapsed or refractory (r/r) classical Hodgkin lymphoma (cHL)....
Anti-programmed cell death-1 (anti-PD-1) therapies have shown a favorable efficacy and good tolerance for relapsed or refractory (r/r) classical Hodgkin lymphoma (cHL). However, there are limited data on long-term outcomes among patients with r/r cHL who achieve an objective response to anti-PD-1 therapies. A total of 260 responders from four, phase 2 clinical trials were included in this study. The median age was 32 years with a male/female ratio of 1.3:1. After a median follow-up period of 31.1 months, 116 (44.6%) responders experienced disease progression and 18 (6.9%) died. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 55.1% and 89.7% overall. Patients with partial remission (PR) had inferior outcomes compared with those who achieved complete remission (3-year PFS, 29.5% vs. 72.3%, P < 0.001; 3-year OS, 81.5% vs. 94.4%, P = 0.017). Moreover, the survival outcome was inferior for patients with refractory disease compared with those with relapsed disease. Multivariate Cox regression analysis showed PR and refractory disease were independent risk factors for PFS. In conclusion, PR and refractory disease have a negative impact on the survival benefit of anti-PD-1 therapeutics in patients with r/r cHL, which highlights the need for multimodal treatment strategies.
Topics: Humans; Female; Male; Adult; Hodgkin Disease; Chronic Disease; Disease Progression; Combined Modality Therapy; Immune Tolerance
PubMed: 37726266
DOI: 10.1038/s41392-023-01600-7 -
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 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 -
Frontiers in Medicine 2023The blockade of interleukine-1 (anakinra and canakinumab) is a well-known highly effective tool for monogenic autoinflammatory diseases (AIDs), such as familial...
INTRODUCTION
The blockade of interleukine-1 (anakinra and canakinumab) is a well-known highly effective tool for monogenic autoinflammatory diseases (AIDs), such as familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, hyperimmunoglobulinaemia D syndrome, and cryopyrin-associated periodic syndrome, but this treatment has not been assessed for patients with undifferentiated AIDs (uAIDs). Our study aimed to assess the safety and efficacy of canakinumab for patients with uAIDs.
METHODS
Information on 32 patients with uAIDs was retrospectively collected and analyzed. Next-generation sequencing and Federici criteria were used for the exclusion of the known monogenic AID.
RESULTS
The median age of the first episode was 2.5 years (IQR: 1.3; 5.5), that of the disease diagnosis was 5.7 years (IQR: 2.5;12.7), and that of diagnostic delay was 1.1 years (IQR: 0.4; 6.1). Patients had variations in the following genes: , and . The main clinical features were fever (100%), rash (91%; maculopapular predominantly), joint involvement (72%), splenomegaly (66%), hepatomegaly (59%), lymphadenopathy (50%), myalgia (28%), heart involvement (31%), intestinal involvement (19%); eye involvement (9%), pleuritis (16%), ascites (6%), deafness, hydrocephalia (3%), and failure to thrive (25%). Initial treatment before canakinumab consisted of non-biologic therapies: non-steroidal anti-inflammatory drugs (NSAID) (91%), corticosteroids (88%), methotrexate (38%), intravenous immunoglobulin (IVIG) (34%), cyclosporine A (25%), colchicine (6%) cyclophosphamide (6%), sulfasalazine (3%), mycophenolate mofetil (3%), hydroxychloroquine (3%), and biologic drugs: tocilizumab (62%), sarilumab, etanercept, adalimumab, rituximab, and infliximab (all 3%). Canakinumab induced complete remission in 27 patients (84%) and partial remission in one patient (3%). Two patients (6%) were primary non-responders, and two patients (6%) further developed secondary inefficacy. All patients with partial efficacy or inefficacy were switched to tocilizumab ( = 4) and sarilumab ( = 1). The total duration of canakinumab treatment was 3.6 (0.1; 8.7) years. During the study, there were no reported Serious Adverse Events (SAEs). The patients experienced non-frequent mild respiratory infections at a rate that is similar as before canakinumab is administered. Additionally, one patient developed leucopenia, but it was not necessary to stop canakinumab for this patient.
CONCLUSION
The treatment of patients with uAIDs using canakinumab was safe and effective. Further randomized clinical trials are required to confirm the efficacy and safety.
PubMed: 38034538
DOI: 10.3389/fmed.2023.1257045 -
Renal Failure Dec 2023This study aimed to assess efficacy of extracorporeal plasma therapy (EPT), including plasmapheresis (PE), immunoadsorption (IA), low-density lipoprotein apheresis...
PURPOSE
This study aimed to assess efficacy of extracorporeal plasma therapy (EPT), including plasmapheresis (PE), immunoadsorption (IA), low-density lipoprotein apheresis (LDL-A), and lymphocytapheresis (LCAP) for adult native kidney patients with primary focal segmental glomerulosclerosis (FSGS).
METHODS
A literature search was conducted using MEDLINE, EMBASE and Cochrane Databases through August 2022. Studies that reported outcomes of EPT in adult native kidneys with primary FSGS were enrolled.
RESULTS
18 studies with 104 therapy-resistant or refractory primary native FSGS patients were identified. Overall EPT response rate was 56%, with long-term benefit of 46%. Of the 101 non-hemodialysis (HD) patients, 54% achieved remission, with 30% complete remission (CR) and 23% partial remission (PR). Of 31 patients with PE, response rate was 65%; CR and PR rates were 27% and 37% in 30 non-HD patients. Of 61 patients with LDL-A, the response rate was 54%; CR and PR rates were 41% and 3% in 29 non-HD patients. Of 10 patients with IA, response rate was 40%. Of 2 patients with LCAP, 1 achieved CR, and one developed renal failure. All 3 HD patients showed increase in urine output and gradual decrease in urine protein excretion following PE ( = 1) or LDL-A ( = 2). 2 of 3 HD patients ultimately discontinued dialysis.
CONCLUSION
EPT with immunosuppressive therapy showed benefit in some patients with refractory primary FSGS, and PE appeared to have a higher response rate.
Topics: Humans; Adult; Glomerulosclerosis, Focal Segmental; Proteinuria; Treatment Outcome; Kidney Transplantation; Kidney; Recurrence
PubMed: 36762994
DOI: 10.1080/0886022X.2023.2176694 -
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