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Kidney & Blood Pressure Research 2023Idiopathic membranous nephropathy (IMN) is the most common form of primary nephrotic syndrome in adults. Antibodies against the M-type phospholipase A2 receptor... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Idiopathic membranous nephropathy (IMN) is the most common form of primary nephrotic syndrome in adults. Antibodies against the M-type phospholipase A2 receptor (PLA2R-ab) are considered as diagnostic biomarkers of IMN.
OBJECTIVE
Here, we performed an updated meta-analysis to assess the diagnostic value of PLA2R-ab for clinical remission in IMN patients.
METHOD
PubMed, Embase, and Cochrane databases were searched for relevant studies published before September 2022. Odds ratios and corresponding 95% confidence intervals were determined using a fixed or random effects model. The heterogeneity among studies was explored by subgroup analysis.
RESULTS
Sixteen studies involving 1,761 IMN participants were included. There were significant differences between PLA2R-ab (+) and PLA2R-ab (-) patients in terms of complete remission (CR) and spontaneous remission. The rates of partial remission (PR) and relapse were similar between the two groups. Patients with PLA2R-ab (-) were at a higher CR rate when treated with a calcineurin inhibitor or a treatment course for 3 months and 6 months, while the spontaneous remission rate was higher in PLA2R-ab seronegative patients from Asia. However, the CR and spontaneous remission rate only significantly declined in IMN patients with the highest titer, but not a middle titer, when compared to those with the lowest titer.
CONCLUSION
In contrast with previous meta-analyses, our results verified that PLA2R-ab can likely predict CR and spontaneous remission in IMN patients, instead of PR and relapse. Race, immunosuppressive agents, and duration of treatment may affect the prognostic value of PLA2R-ab. Considering that the remission rate of IMN patients with a middle level of PLA2R-ab was not different from that of patients with the lowest level, a proper cut-off value of PLA2R-ab for prognosis should be clarified.
Topics: Adult; Humans; Glomerulonephritis, Membranous; Receptors, Phospholipase A2; Remission, Spontaneous; Antibodies; Prognosis; Pathologic Complete Response; Recurrence
PubMed: 36720217
DOI: 10.1159/000529415 -
Diabetologia Apr 2023Sex differences are present in cardiovascular care and in outcomes among adults with type 1 diabetes mellitus, which typically commences in childhood. Whether sex... (Review)
Review
AIMS/HYPOTHESIS
Sex differences are present in cardiovascular care and in outcomes among adults with type 1 diabetes mellitus, which typically commences in childhood. Whether sex influences care and outcomes in childhood is not known. This systematic review provides an overview of sex differences in children with type 1 diabetes, focusing on patient and disease characteristics, treatment, comorbidities and complications.
METHODS
Literature in MEDLINE up to 15 June 2021 was searched, using the terms diabetes mellitus, sex characteristics, sex distribution, children and/or adolescents. All primary outcome studies on children with type 1 diabetes that mentioned a sex difference in outcome were included, with the exception of qualitative studies, case reports or case series. Studies not pertaining to the regular clinical care process and on incidence or prevalence only were excluded. Articles reporting sex differences were identified and assessed on quality and risk of bias using Joanna Briggs Institute critical appraisal tools. Narrative synthesis and an adapted Harvest plot were used to summarise evidence by category.
RESULTS
A total of 8640 articles were identified, rendering 90 studies for review (n=643,217 individuals). Studies were of observational design and comprised cohort, cross-sectional and case-control studies. Most of the included studies showed a higher HbA in young female children both at diagnosis (seven studies, n=22,089) and during treatment (20 out of 21 studies, n=144,613), as well as a steeper HbA increase over time. Many studies observed a higher BMI (all ages, ten studies, n=89,700; adolescence, seven studies, n=33,153), a higher prevalence of being overweight or obese, and a higher prevalence of dyslipidaemia among the female sex. Hypoglycaemia and partial remission occurred more often in male participants, and ketoacidosis (at diagnosis, eight studies, n=3561) and hospitalisation was more often seen in female participants. Most of the findings showed that female participants used pump therapy more frequently (six studies, n=211,324) and needed higher insulin doses than male participants. Several comorbidities, such as thyroid disease and coeliac disease, appeared to be more common in female participants. All studies reported lower quality of life in female participants (15 studies, n=8722). Because the aim of this study was to identify sex differences, studies with neutral outcomes or minor differences may have been under-targeted. The observational designs of the included studies also limit conclusions on the causality between sex and clinical outcomes.
CONCLUSIONS/INTERPRETATION
Sex disparities were observed throughout diabetes care in children with type 1 diabetes. Several outcomes appear worse in young female children, especially during adolescence. Focus on the cause and treatment of these differences may provide opportunities for better outcomes.
REGISTRATION
This systematic review is registered in PROSPERO (CRD42020213640).
Topics: Child; Adult; Adolescent; Humans; Female; Male; Diabetes Mellitus, Type 1; Sex Characteristics; Quality of Life; Cross-Sectional Studies; Insulin
PubMed: 36700969
DOI: 10.1007/s00125-022-05866-4 -
The Journal of International Medical... Jan 2023To conduct a meta-analysis assessing the efficacy and safety of cyclosporine-based combinations for primary immune thrombocytopenia (ITP). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To conduct a meta-analysis assessing the efficacy and safety of cyclosporine-based combinations for primary immune thrombocytopenia (ITP).
METHODS
Randomized controlled clinical trials were collected by systematically searching databases (PubMed®, MEDLINE®, EMBASE, The Cochrane Library, China National Knowledge Infrastructure) from inception to June 2022. All studies included patients with ITP who received cyclosporine-based regimens. We performed comprehensive analyses of the overall response rate (ORR), complete response (CR) rate, partial response (PR) rate, relapse rate, platelet count, and adverse drug reaction (ADR) rate.
RESULTS
Seven studies (n = 418) were ultimately included. According to a fixed-effects model, cyclosporine-based combinations improved the ORR and CR rate and reduced the relapse rate. The ADR rate was not increased in the cyclosporine-based combination group. Cyclosporine-based regimens effectively increased the platelet count. Subgroup analysis illustrated that cyclosporine-based combinations were linked to higher ORRs in both children (odds ratio [OR] = 5.74, 95% confidence interval [CI] = 1.79-18.41) and adults (OR = 5.46, 95% CI = 2.48-12.02) and a higher CR rate in adults (OR = 2.97, 95% CI = 1.56-5.63).
CONCLUSION
Cyclosporine exhibited efficacy in the treatment of ITP without increasing the risk of ADRs.
Topics: Child; Adult; Humans; Purpura, Thrombocytopenic, Idiopathic; Cyclosporine; Platelet Count; Clinical Protocols; Remission Induction
PubMed: 36650914
DOI: 10.1177/03000605221149870 -
Seminars in Arthritis and Rheumatism Apr 2023The search for new glucocorticoid-sparing disease-modifying anti-rheumatic drugs continues to be an unmet need in large vessel vasculitis (LVV). This report aims to... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The search for new glucocorticoid-sparing disease-modifying anti-rheumatic drugs continues to be an unmet need in large vessel vasculitis (LVV). This report aims to assess the effectiveness and safety of leflunomide (LEF) in Takayasu arteritis (TA) and giant cell arteritis (GCA).
METHODS
We systematically reviewed the literature, searching for studies evaluating the efficacy of LEF in LVV. A meta-analysis was conducted using the random-effects method.
RESULTS
The literature search identified eight studies that assessed LEF in TAK and seven in GCA. All were uncontrolled observational studies with a high risk of bias, implying a low or very-low certainty of evidence. In TAK, the pooled proportion of patients achieving at least a partial remission was 75% (95% CI: 0.64-0.84), angiographic stabilization was observed in 86% (0.77-0.94) and relapses in 12% (0.05-0.21). The mean reduction in the prednisolone dose (MRPD) after LEF treatment was 15.7 mg/d (10.28-21.16). Adverse events were observed in 8% of patients (0.02-0.16). Comparison of LEF with methotrexate (MTX) or cyclophosphamide revealed LEF to be superior in terms of remission induction, relapse prevention, and tolerance. When compared with tofacitinib, both drugs demonstrated comparable efficacy. In GCA, the pooled proportion of patients achieving at least a partial remission was 60% (0.17-0.95). The MRPD after LEF treatment was 15.63 mg/d (1.29-32.55) and 53% of the patients were able to discontinue glucocorticoids (0.25 - 0.80). Relapses were observed in 21% of cases (0.14- 0.28) and adverse events in 28% (0.12-0.46). Comparison of LEF with MTX showed similar efficacy and tolerance.
CONCLUSION
LEF is well tolerated and might be effective for patients with TAK and GCA.
Topics: Humans; Leflunomide; Antirheumatic Agents; Methotrexate; Giant Cell Arteritis; Takayasu Arteritis; Glucocorticoids; Cohort Studies; Recurrence
PubMed: 36645992
DOI: 10.1016/j.semarthrit.2023.152166 -
International Journal of Environmental... Dec 2022Immune checkpoint inhibitors (ICIs) are recommended for various types of cancer. On the other hand, these ICIs may cause immune-related adverse events (irAEs). Lichen... (Review)
Review
INTRODUCTION
Immune checkpoint inhibitors (ICIs) are recommended for various types of cancer. On the other hand, these ICIs may cause immune-related adverse events (irAEs). Lichen sclerosus (LS) and lichen planus (LP) are two distinct phenotypes of irAEs that occur in a subset of patients treated with ICIs. These adverse effects have a detrimental effect on the patient's quality of life and treatment phases; however, the clinical evaluation and assessment of LS and LP remain uncertain. This study aims to assess and evaluate the risk of LS and LP associated with the use of ICIs via a systematic review of the literature and the USA FDA Adverse Events FAERS database.
METHOD
The study searched electronic databases such as PubMed, Medline, Cochrane, and Google Scholar for case reports on immune-checkpoint-inhibitor-associated lichen sclerosus and lichen planus published in English between inception and 31 December 2021. The FDA's adverse event reporting system (FAERS) database was also analyzed.
RESULTS
Thirty-eight case reports and two retrospective studies with a total of 101 patients, in addition to the FAERS data, were evaluated. More cases involved lichen planus (78.9%) than lichen sclerosis (21%). Nivolumab and pembrolizumab were most frequently reported with LS and LP, among other ICIs. Thirty-six out of thirty-eight patients with LS or LP experienced complete remission, while two patients experienced partial remission. Most of the cases had an excellent response to corticosteroids (92.1%), while the remainder had moderate (5.2%) and poor (2.6%) responses. Additionally, the reporting odds ratio (ROR) of the FAERS database indicated a favorable association for ICIs, the risk of LP, and LS. A stronger association was uniquely found between nivolumab and pembrolizumab.
CONCLUSION
There have been published case reports for these adverse events. Healthcare providers should be aware of the possibility of lichen sclerosis and lichen planus developing in patients receiving ICIs which could necessitate hospitalization or discontinuation. Regulatory agencies are advised to monitor the risks as a potential safety signal.
Topics: Humans; Immune Checkpoint Inhibitors; Lichen Planus; Lichen Sclerosus et Atrophicus; Nivolumab; Quality of Life; Retrospective Studies
PubMed: 36612904
DOI: 10.3390/ijerph20010580 -
Zeitschrift Fur Rheumatologie Nov 2023The purpose of this study was to compare the efficacy and safety of tacrolimus and mycophenolate mofetil (MMF) as induction therapy and low-dose tacrolimus as treatment... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The purpose of this study was to compare the efficacy and safety of tacrolimus and mycophenolate mofetil (MMF) as induction therapy and low-dose tacrolimus as treatment for lupus nephritis (LN).
METHODS
Meta-analysis of randomized controlled trials (RCTs) was conducted to compare the efficacy and safety of tacrolimus and MMF as induction therapy for LN. We systematically reviewed RCTs and prospective cohort studies with a tacrolimus dose of 3 mg daily and performed a meta-analysis of the efficacy and safety of tacrolimus as an induction treatment for LN in comparison to MMF.
RESULTS
The inclusion criteria were satisfied by eight studies (five RCTs and three prospective cohort studies) with a total of 408 individuals (289 for tacrolimus vs. MMF and 119 for low-dose tacrolimus). Tacrolimus and MMF had similar complete remission rates (odds ratio [OR] 1.028; 95% confidence interval [CI] 0.589-1.796; p = 0.922). The partial remission rate did not differ between the tacrolimus and MMF groups (OR 1.400; 95% CI 0.741-2.646; p = 0.300). Tacrolimus and MMF showed no differences in proteinuria, serum albumin, serum creatinine, creatinine clearance, renal Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), or extra-renal SLEDAI. The incidence of infection, severe infection, leukopenia, and hyperglycemia did not differ between the tacrolimus and MMF groups. However, herpes zoster infection was significantly less common in the tacrolimus group (OR 0.137; 95% CI 0.034-0.546; p = 0.005), whereas serum creatinine elevation was significantly higher in the tacrolimus group than in the MMF group (OR 8.148; 95% CI 1.369-48.50; p = 0.021). At 3 mg/d, tacrolimus was shown to be safe, well tolerated, and offered therapeutic benefits in all investigations.
CONCLUSION
Tacrolimus was comparable to MMF in terms of effectiveness and safety as an induction therapy for LN, with the exception of a reduced risk of herpes zoster infection and a rise in serum creatinine. In individuals with LN, 3 mg/d tacrolimus was proven to be efficacious and safe.
Topics: Humans; Tacrolimus; Lupus Nephritis; Mycophenolic Acid; Immunosuppressive Agents; Cyclophosphamide; Creatinine; Treatment Outcome; Herpes Zoster
PubMed: 36607421
DOI: 10.1007/s00393-022-01313-2 -
Hematology (Amsterdam, Netherlands) Dec 2023Amyloid light-chain (AL) amyloidosis is a rare disease characterized by amyloid fibril deposits made up of toxic light chains causing progressive organ dysfunction and... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Amyloid light-chain (AL) amyloidosis is a rare disease characterized by amyloid fibril deposits made up of toxic light chains causing progressive organ dysfunction and death. Recent studies suggest that hematologic response may be an important prognostic indicator of overall survival (OS) in AL amyloidosis. The aim of this study was to evaluate the trial-level association between hematologic complete response (CR) or very good partial response or better (≥ VGPR) and OS in newly diagnosed patients.
METHODS
Studies were identified via systematic literature review. Pooled effect estimates were generated by a random-effects model.
RESULTS
Nine observational studies reporting hematologic CR or ≥VGPR and OS hazard ratios (HRs) were included in the meta-analysis. Achieving hematologic CR was associated with improved OS (HR, 0.21; 95% confidence interval [CI] 0.13-0.34). Achieving ≥ VGPR was also associated with improved OS (HR 0.21; 95% CI 0.17-0.26). Results of a sensitivity analysis excluding one outlier study revealed no heterogeneity and a better overall HR estimate. Potential limitations of this meta-analysis include the small number of eligible studies (consistent with the rarity of the disease) and inconsistencies in reporting of results.
CONCLUSIONS
Overall, our findings support the use of deep hematologic response (CR or ≥VGPR) as a clinical trial endpoint in newly diagnosed AL amyloidosis. This study provides evidence that early hematologic response is a strong patient-level surrogate for long-term OS in patients with AL amyloidosis receiving frontline therapy. Structured data collection of depth of response in future trials will further strengthen these observations.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Prognosis; Remission Induction; Proportional Hazards Models
PubMed: 36607151
DOI: 10.1080/16078454.2022.2157581 -
Nutrients Dec 2022Exclusive enteral nutrition (EEN) is recommended as a first-line therapy to induce remission of Crohn's disease (CD) and is considered as effective as corticosteroid... (Review)
Review
Exclusive enteral nutrition (EEN) is recommended as a first-line therapy to induce remission of Crohn's disease (CD) and is considered as effective as corticosteroid treatment. However, the dietary restriction causes lack of adherence and poor tolerance to the therapy. Partial enteral nutrition (PEN), which allows for the ingestion of some food, could be a better tolerated alternative, but it is unknown whether it is as effective at inducing CD remission as EEN. The aim of this systematic review is to analyze the available evidence on PEN as a remission induction therapy in CD. A literature search was conducted using the MEDLINE (via PUBMED) and Cochrane Library databases following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Clinical trials in pediatric and adult patients were included. The risk of bias was assessed following the Cochrane Collaboration methodology. The selected studies showed variable but high response rates to PEN and EEN. Limitations regarding the wide heterogeneity between the studies included in this review should be considered. Although more studies are needed, according to our results, PEN combined with a highly restrictive diet seems to be as effective as EEN in inducing remission of CD.
Topics: Adult; Humans; Child; Enteral Nutrition; Crohn Disease; Remission Induction; Food, Formulated; Adrenal Cortex Hormones; Randomized Controlled Trials as Topic
PubMed: 36558422
DOI: 10.3390/nu14245263 -
Surgical Endoscopy May 2023Thymectomy has been utilized as a treatment for Myasthenia Gravis (MG) for many decades, with both open and minimally invasive surgical (MIS) techniques currently used.... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Thymectomy has been utilized as a treatment for Myasthenia Gravis (MG) for many decades, with both open and minimally invasive surgical (MIS) techniques currently used. Although MIS has shown improved short-term results, long-term effects remain uncertain. This systematic review and meta-analysis aim to compare the post-operative and long-term outcomes of MIS versus open thymectomy in MG patients.
METHODS
MEDLINE, EMBASE and CENTRAL databases were searched from inception till January 2022 for keywords related to MG and open or MIS thymectomy. Primary outcome was complete stable remission (CSR), and secondary outcomes were clinical improvement, complications, length of stay, operation time, and blood loss. Grading of recommendations, assessment, development, and evaluation was used to assess the certainty of evidence.
RESULTS
26 studies with 3588 patients were included in the analysis. At 1, 3 and 5 years, there was no statistical difference noted in CSR between open versus MIS thymectomy. However, CSR was improved at 1 year for MIS thymectomy in non-thymomatous MG (P = 0.03). There was no significant difference in rates of partial clinical improvement between techniques at 1-year. Although analyses on length of hospital stay and blood loss showed improvement following MIS thymectomy, operative time was shorter for open thymectomy.
CONCLUSION
This is the first systematic review and meta-analysis assessing long-term effects of MIS versus open thymectomy in MG patients. Given the lack of significant differences noted, either MIS or open thymectomy can be performed, based on surgeon preference. Further high-level, long-term research should be conducted to determine the benefit of each technique.
Topics: Humans; Thymectomy; Myasthenia Gravis; Remission Induction; Length of Stay; Minimally Invasive Surgical Procedures; Treatment Outcome; Retrospective Studies
PubMed: 36539629
DOI: 10.1007/s00464-022-09757-y -
Frontiers in Pharmacology 2022The (R)-CDOP combination regimen, based on pegylated liposomal doxorubicin, is increasingly used for elderly patients with non-Hodgkin's lymphoma. However, the...
Cardiovascular adverse events associated with cyclophosphamide, pegylated liposomal doxorubicin, vincristine, and prednisone with or without rituximab ((R)-CDOP) in non-Hodgkin's lymphoma: A systematic review and meta-analysis.
The (R)-CDOP combination regimen, based on pegylated liposomal doxorubicin, is increasingly used for elderly patients with non-Hodgkin's lymphoma. However, the cardiotoxicity and efficacy of the (R)-CDOP regimen compared with conventional anthracyclines have not been demonstrated in the general population. Therefore, this systematic review and meta-analysis evaluated the risk of cardiotoxicity and efficacy associated with the (R)-CDOP regimen in patients with non-Hodgkin's lymphoma. PubMed, Embase, Cochrane Library, CNKI, WanFang Database, and VIP were searched. The search covered the period from the start of the clinical use of (R)-CDOP to April 2022. We searched the literature for cardiovascular adverse events associated with (R)-CDOP in non-Hodgkin's lymphoma. The data were analyzed using R 4.2.0 and Stata 12.0. From the included studies, the important findings were as follows: total cardiovascular event rate, 7.45% (95% confidence interval [CI] = 4.86%-10.44%); non-serious cardiovascular adverse event rate, 6.48% (95% CI = 3.70%-9.8%); serious cardiovascular adverse event rate, 0.67% (95% CI = 0.00%-2.12%); heart failure rate, 0.55% (95% CI = 0.00%-1.93%); rate of treatment discontinuation attributable to left ventricular dysfunction or heart failure, 0.02% (95% CI = 0.00%-0.57%); and cardiovascular death rate, 0.00% (95% CI = 0.00%-0.37%). Compared with the (R)-CHOP regimen, the (R)-CDOP regimen reduced the risk of cardiovascular events, including total cardiovascular adverse events (odds ratio [OR] = 0.161, 95% CI = 0.103-0.251, < 0.001, and NNT = 3.7), non-serious cardiovascular adverse events (OR = 0.171, 95% CI = 0.093-0.314, < 0.001, and NNT = 3.6), serious cardiovascular adverse events (OR = 0.252, 95% CI = 0.119-0.535, < 0.001, and NNT = 6.8), and heart failure (OR = 0.294, 95% CI = 0.128-0.674, = 0.004, and NNT = 9.5). To evaluate the survival benefits, we compared (R)-CDOP and (R)-CHOP regimens. We found that the (R)-CDOP regimen was no less efficacious, including complete remission (CR) (OR = 1.398, 95% CI = 0.997-1.960, and = 0.052), partial response (PR) (OR = 1.631, 95% CI = 1.162-2.289, and = 0.005), objective response rate (ORR) (OR = 2.236, 95% CI = 1.594-3.135, and < 0.001), stable disease (SD) (OR = 0.526, 95% CI = 0.356-0.776, and = 0.001), and progressive disease (PD) (OR = 0.537, 95% CI = 0.323-0.894, and = 0.017). Our findings suggested that the (R)-CDOP regimen had a lower risk of cardiovascular adverse events in non-Hodgkin's lymphoma than the (R)-CHOP regimen, demonstrating its safety with regard to cardiotoxicity. In addition, this study found the (R)-CDOP regimen was no less efficacious than the (R)-CHOP regimen in the treatment of non-Hodgkin's lymphoma. These findings need to be validated by higher-quality research because of the limited number and quality of included studies.
PubMed: 36532720
DOI: 10.3389/fphar.2022.1060668