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Advances in Rheumatology (London,... Jun 2024To develop the second evidence-based Brazilian Society of Rheumatology consensus for diagnosis and treatment of lupus nephritis (LN).
OBJECTIVE
To develop the second evidence-based Brazilian Society of Rheumatology consensus for diagnosis and treatment of lupus nephritis (LN).
METHODS
Two methodologists and 20 rheumatologists from Lupus Comittee of Brazilian Society of Rheumatology participate in the development of this guideline. Fourteen PICO questions were defined and a systematic review was performed. Eligible randomized controlled trials were analyzed regarding complete renal remission, partial renal remission, serum creatinine, proteinuria, serum creatinine doubling, progression to end-stage renal disease, renal relapse, and severe adverse events (infections and mortality). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to develop these recommendations. Recommendations required ≥82% of agreement among the voting members and were classified as strongly in favor, weakly in favor, conditional, weakly against or strongly against a particular intervention. Other aspects of LN management (diagnosis, general principles of treatment, treatment of comorbidities and refractory cases) were evaluated through literature review and expert opinion.
RESULTS
All SLE patients should undergo creatinine and urinalysis tests to assess renal involvement. Kidney biopsy is considered the gold standard for diagnosing LN but, if it is not available or there is a contraindication to the procedure, therapeutic decisions should be based on clinical and laboratory parameters. Fourteen recommendations were developed. Target Renal response (TRR) was defined as improvement or maintenance of renal function (±10% at baseline of treatment) combined with a decrease in 24-h proteinuria or 24-h UPCR of 25% at 3 months, a decrease of 50% at 6 months, and proteinuria < 0.8 g/24 h at 12 months. Hydroxychloroquine should be prescribed to all SLE patients, except in cases of contraindication. Glucocorticoids should be used at the lowest dose and for the minimal necessary period. In class III or IV (±V), mycophenolate (MMF), cyclophosphamide, MMF plus tacrolimus (TAC), MMF plus belimumab or TAC can be used as induction therapy. For maintenance therapy, MMF or azathioprine (AZA) are the first choice and TAC or cyclosporin or leflunomide can be used in patients who cannot use MMF or AZA. Rituximab can be prescribed in cases of refractory disease. In cases of failure in achieving TRR, it is important to assess adherence, immunosuppressant dosage, adjuvant therapy, comorbidities, and consider biopsy/rebiopsy.
CONCLUSION
This consensus provides evidence-based data to guide LN diagnosis and treatment, supporting the development of public and supplementary health policies in Brazil.
Topics: Lupus Nephritis; Humans; Immunosuppressive Agents; Brazil; Societies, Medical; Creatinine; Proteinuria; Mycophenolic Acid; Antibodies, Monoclonal, Humanized; Rheumatology; Rituximab; Biopsy; Cyclophosphamide; Leflunomide; Glucocorticoids; Hydroxychloroquine; Azathioprine; Remission Induction; Cyclosporine; Evidence-Based Medicine; Consensus; Disease Progression; Kidney Failure, Chronic; Randomized Controlled Trials as Topic
PubMed: 38890752
DOI: 10.1186/s42358-024-00386-8 -
International Immunopharmacology Jun 2024To evaluate the efficacy and safety of Janus kinases inhibitors (JAKi) for adult-onset Still's disease (AOSD) patients. (Review)
Review
OBJECTIVE
To evaluate the efficacy and safety of Janus kinases inhibitors (JAKi) for adult-onset Still's disease (AOSD) patients.
METHODS
We searched the Embase, PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), and the China National Knowledge Infrastructure (CNKI) from inception up to 22 October 2023. The results were supplemented by a backward search of relevant publications. Two authors independently selected trials. The available studies were comprehensively reviewed and analysed.
RESULTS
A total of 9 studies with a total of 35 patients were included in the review. Of these patients, 17 (48.6%) patients were treated with tofacitinib, 14 (40%) with baricitinib, 4 (11.4%) with ruxolitinib and 1 (2.9%) with upadacitinib. After treatment with JAKi, 17 (48.6%) patients showed complete remission, 12 (34.3%) patients showed partial remission, and 7 (20%) patients showed loss of efficacy or relapse. The use of ruxolitinib showed a remission rate of 100% in AOSD patients with macrophage activation syndrome (MAS). The incidence of adverse events (AEs) reported were mild and rare overall. Most AEs were abnormal lipid parameters (9.7%), bacterial pneumonia (3.2%), organised pneumonia (3.2%), diarrhoea (3.2%), increased heart rate (3.2%), menometrorrhagia (3.2%) and leukopenia (3.2%). One patient died from bacterial pneumonia.
CONCLUSION
JAKi therapy may be an option for patients with AOSD, especially for refractory AOSD. For patients with AOSD complicated by MAS, ruxolitinib seems to be a better choice than other JAKi agents. Although our study shows that JAKi are well tolerated in AOSD patients, we still need to be on the lookout for fatal infections.
PubMed: 38870881
DOI: 10.1016/j.intimp.2024.112451 -
Frontiers in Pharmacology 2024FLT3 mutations are closely associated with the occurrence of hematological and solid malignancies, especially with acute myeloid leukemia. Currently, several FLT3...
FLT3 mutations are closely associated with the occurrence of hematological and solid malignancies, especially with acute myeloid leukemia. Currently, several FLT3 inhibitors are in clinical trials, and some have been applied in clinic. However, the safety, efficacy and pharmacodynamics of these FLT3 inhibitors have not been systemically analyzed before. We searched and reviewed clinical trial reports on the monotherapy of 13 FLT3 inhibitors, including sorafenib, lestaurtinib, midostaurin, gilteritinib, quizartinib, sunitinib, crenolanib, tandutinib, cabozantinib, pexidartinib, pacritinib, famitinib, and TAK-659 in patients with hematological and solid malignancies before May 31, 2023. Our results showed the most common adverse events (AEs) were gastrointestinal adverse reactions, including diarrhea, hand-foot syndrome and nausea, while the most common hematological AEs were febrile neutropenia, anemia, and thrombocytopenia. Based on the published data, the mean overall survival (OS) and the mean progression-free survival (PFS) were 9.639 and 5.905 months, respectively. The incidence of overall response rate (ORR), complete remission (CR), partial response (PR), and stable disease (SD) for all these FLT3 inhibitors was 29.0%, 8.7%, 16.0%, and 42.3%, respectively. The ORRs of FLT3 inhibitors in hematologic malignancies and solid tumors were 40.8% and 18.8%, respectively, indicating FLT3 inhibitors were more effective for hematologic malignancies than for solid tumors. In addition, time to maximum plasma concentration () in these FLT3 inhibitors ranged from 0.7-12.0 hours, but the elimination half-life () range was highly variable, from 6.8 to 151.8 h. FLT3 inhibitors monotherapy has shown significant anti-tumor effect in clinic, and the effectiveness may be further improved through combination medication.
PubMed: 38828446
DOI: 10.3389/fphar.2024.1294668 -
The Journal of Evidence-based Dental... Jun 2024Despite phototherapy (in the form of photodynamic therapy (PDT)-mediated oxidative stress) being utilized in the management of oral potentially malignant disorders... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Despite phototherapy (in the form of photodynamic therapy (PDT)-mediated oxidative stress) being utilized in the management of oral potentially malignant disorders (OPMDs), the evidence of certainty remains unclear. Hence, this systematic review and meta-analysis (PROSPERO # CRD42021218748) is aimed to evaluate the clinical efficacy of PDT-induced oxidative stress in OPMDs METHODS: PubMed, Embase, Web of Science, Scopus, and Cochrane Library databases were searched without restriction of language or year of publication. In addition, gray literature was searched and a manual search was performed. Two independent reviewers screened all the studies, assessing data extraction, risk of bias and certainty of evidence. A narrative synthesis was carried out. For the meta-analysis, random effects were considered to determine the prevalence of a total and a partial remission (PR) of oral potentially malignant disorders (OPMDs). The certainty of evidence was explored using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.
RESULTS
Twenty-three studies were included in the qualitative and quantitative syntheses. A total of 880 patients were included (564 males; 218 females) with an age range between 24 and 89-years-old. The results showed the prevalence of the total and partial remissions respectively for the following OPMLs: actinic cheilitis (AC): 69.9% and 2.4%; oral leukoplakia (OL): 44% and 36.9%; oral verrucous hyperplasia (OVH): 98.5%; oral erythroleukoplakia (OEL): 92.1% and 7.9%. The prevalence of no remission of OL was 18.8%.
CONCLUSIONS
PDT demonstrated significant results in clinical remission of OPMDs and most of the eligible studies have shown a total or a partial remission of the included lesions, but at a low or a very low certainty of evidence. Hence, further clinical studies with robust methodology are warranted to offer further validated data. Also, further evidence is required to understand further the mechanism of PDT-induced oxidative stress.
Topics: Aged; Aged, 80 and over; Female; Humans; Male; Cheilitis; Mouth Neoplasms; Oxidative Stress; Photochemotherapy; Photosensitizing Agents; Precancerous Conditions; Treatment Outcome; Adult; Middle Aged
PubMed: 38821659
DOI: 10.1016/j.jebdp.2023.101899 -
Cureus Apr 2024Pemphigus vulgaris (PV) is a chronic autoimmune blistering disorder characterized by the loss of intraepithelial adhesion, affecting the skin and mucous membranes. Both... (Review)
Review
Pemphigus vulgaris (PV) is a chronic autoimmune blistering disorder characterized by the loss of intraepithelial adhesion, affecting the skin and mucous membranes. Both males and females are affected, although it predominantly affects females in their fifth and sixth decades of life. Approximately 1.4 to 3.7% of PV cases occur in the pediatric population (≤18 years of age), and may be classified into childhood/pediatric PV, which affects individuals under 12 years old, and juvenile/adolescent PV, affecting those between 12 and 18 years old. Due to its rare occurrence in children and adolescents, there is often a delay in diagnosis and treatment in this age group. A systematic literature search was conducted on MEDLINE/PubMed, Web of Science, EMBASE, SCOPUS, and Cochrane Library databases to evaluate the efficacy of rituximab (RTX) in childhood and juvenile PV patients. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist was employed to assess the risk of bias in case reports and series, while the Cochrane ROBINS-I tool was utilized for evaluating observational studies or non-randomized intervention studies. A total of 18 studies encompassing 46 juvenile or childhood PV patients in the pediatric and adolescent age groups were included for qualitative synthesis. The studies included nine case reports, two case series, five retrospective studies, one prospective study, and one open-label pilot study. Almost all cases of childhood and juvenile PV achieved either complete or partial remission after undergoing RTX treatment during the final follow-up periods. Furthermore, most cases reported no relapse, and only minor adverse events were noted in the RTX treatment group. Despite its potential benefits, the utilization of RTX in pediatric patients raises concerns due to the scarcity of evidence and the absence of controlled studies specific to this age group. Further exploration is necessary to establish a standardized treatment regimen for RTX in pediatric PV, which involves identifying the optimal dosage, frequency, treatment cycle duration, and maintenance therapy duration.
PubMed: 38752055
DOI: 10.7759/cureus.58288 -
Biomedicines Mar 2024The recurrence of idiopathic membranous nephropathy (iMN) after kidney transplantation is common, although its exact clinical significance remains unclear. This... (Review)
Review
INTRODUCTION
The recurrence of idiopathic membranous nephropathy (iMN) after kidney transplantation is common, although its exact clinical significance remains unclear. This systematic review aims to elucidate the effects of iMN recurrence on graft survival.
MATERIALS AND METHODS
A literature search was performed by systematically searching Medline, Scopus, Web of Science, and Google Scholar from inception. Cohort studies examining iMN recurrence after kidney transplantation were deemed eligible. Meta-analysis was performed by fitting random-effects models.
RESULTS
Twelve (12) articles published from 1995 to 2016 reporting on 139 transplant patients with recurrent iMN were included. The median time of the diagnosis of recurrent iMN was 18 months during follow-up from 35 to 120 months. Risk factors for iMN recurrence in the renal allograft are a positive serum test for anti-PLA2R antibodies pretransplant, female sex, younger age, high proteinuria pretransplant, the longest interval from initial disease to end-stage chronic kidney disease, and the combination of alleles HLA DQA1 05:01 and HLA DQB1 02:01. In the pretransplant period, 37 (26.61%) patients had a positive serum test and 18 (12.94%) patients had a positive biopsy stain for anti-PLA2R antibodies. The sensitivity of the pretransplant positive serum test for these antibodies ranges from 57% to 85.30% and the specificity is 85.10-100%. A total of 81.80% of patients who received rituximab as treatment for iMN recurrence achieved complete and partial remission, while 18.20% had no response to treatment. iMN recurrence was not associated with significantly different rates of graft loss (odds ratio = 1.03, 95% CI: 0.52-2.04, = 0.524, I = 0.00%). Recurrence of iMN was not associated with increased risk of graft loss independently of whether patients were treated with rituximab (OR: 0.98, 95% CI: 0.39-2.50, I: 0%) or not (OR: 1.22, 95% CI: 0.58-2.59, I: 3.8%). Patients with iMN recurrence who achieved remission had significantly reduced risk of graft loss (OR: 0.14, 95% CI: 0.03 to 0.73).
CONCLUSION
The main outcome from this systematic review is that there is no statistically significant difference in graft survival in patients with iMN recurrence compared to those without recurrence in long-term follow-up. The achievement of remission is associated with significantly reduced risk of graft loss.
PubMed: 38672095
DOI: 10.3390/biomedicines12040739 -
Frontiers in Oncology 2024Pancreatic cancer is a highly aggressive malignancy with limited response to chemotherapy. This research aims to compare the effectiveness and safety of regional...
INTRODUCTION
Pancreatic cancer is a highly aggressive malignancy with limited response to chemotherapy. This research aims to compare the effectiveness and safety of regional intra-arterial chemotherapy (RIAC) with conventional systemic chemotherapy in treating advanced stages of pancreatic cancer.
METHODS
A comprehensive literature review was conducted using databases such as PubMed, Embase, Web of Science, and the Cochrane Library. Studies assessing the comparative outcomes of RIAC and systemic chemotherapy were included. Data extraction and quality evaluation were performed independently by two researchers. Statistical analysis was conducted using STATA16 software, calculating odds ratios (OR), risk differences (RD), and 95% confidence intervals (CI).
RESULTS
Eleven studies, comprising a total of 627 patients, were included in the meta-analysis. The findings showed that patients undergoing RIAC had significantly higher rates of partial remission (PR) compared to those receiving systemic chemotherapy (OR = 2.23, 95% CI: 1.57, 3.15, I2= 0%). Additionally, the rate of complications was lower in the RIAC group (OR = 0.45, 95% CI: 0.33, 0.63, I2= 0%). Moreover, patients treated with RIAC had notably longer median survival times.
DISCUSSION
The results of this research indicate that RIAC is associated with a higher rate of partial remission, improved clinical benefits, and fewer complications compared to systemic chemotherapy in the management of advanced pancreatic cancer. These findings suggest that RIAC may be a more effective and safer treatment option for patients with advanced stages of pancreatic cancer.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023404637.
PubMed: 38651152
DOI: 10.3389/fonc.2024.1197424 -
Nutrients Mar 2024Crohn's disease (CD) is an inflammatory bowel disease. Previous research has explored the impact of diet on CD, as specific dietary components can influence gut... (Review)
Review
Crohn's disease (CD) is an inflammatory bowel disease. Previous research has explored the impact of diet on CD, as specific dietary components can influence gut microbiota and immune responses, contributing to damage in the gastrointestinal tract. The Crohn's Disease Exclusion Diet (CDED) is based on an exclusion diet; it is a recent dietary approach that is often used alongside partial enteral nutrition (PEN) and aims to induce disease remission by excluding certain dietary components. This study assesses the current evidence for the effectiveness of the CDED + PEN in achieving remission in both children and adults with active CD. Our systematic review followed PRISMA recommendations and was registered in PROSPERO with CRD number 42022335076. The searched databases were PubMed/MEDLINE, Cochrane Library, Scopus, and Web of Science. The included studies were analyzed using Rayyan software, and the risk of bias was assessed with Cochrane RevMan 5.0 software. The primary assessed outcome was clinical remission, evaluated with validated questionnaire scores such as PCDAI, CDAI, or HBI. All analyzed papers yielded promising results. Notably, the CDED + PEN demonstrated better tolerance than exclusive enteral nutrition (EEN), resulting in higher adherence rates. Therefore, the CDED + PEN appears to be a viable alternative for induction remission in active disease for both children and adults with CD.
Topics: Adult; Child; Humans; Crohn Disease; Inflammatory Bowel Diseases; Causality; Databases, Factual
PubMed: 38613020
DOI: 10.3390/nu16070987 -
Heliyon Apr 2024Idiopathic membranous nephropathy (IMN) is a rare autoimmune disorder that causes nephrotic syndromes in adults. Conventional immunosuppressive therapies often exhibit...
BACKGROUND
Idiopathic membranous nephropathy (IMN) is a rare autoimmune disorder that causes nephrotic syndromes in adults. Conventional immunosuppressive therapies often exhibit limited efficacy in achieving remission and may result in notable adverse reactions, warranting the exploration of novel therapeutic approaches for IMN treatment. Traditional Chinese medicine (TCM), which is extensively used for kidney disease management, is a promising alternative.
OBJECTIVE
This study aimed to examine the safety and efficacy of TCM alone or in combination with Western medicine for the management of patients diagnosed with IMN.
METHODS
This study employed a systematic search of English and Chinese electronic databases to identify randomized controlled trials (RCTs) that examined the application of TCM in the treatment of IMN. RCTs that met the predetermined inclusion and exclusion criteria and assessed the safety and efficacy of TCM alone or in combination with Western medicine in patients with IMN were included in the analysis. The methodological quality of the included studies was evaluated by using a risk-of-bias tool. All statistical analyses were performed using the RevMan software (version 5.4.2). The evidence was evaluated on the https://www.gradepro.org/website.
RESULTS
This study included 29 randomized controlled trials (RCTs) involving 1982 patients with moderate methodological quality that met the inclusion criteria. The results showed that, compared to Western medicine alone therapy, the use of TCM alone or in combination with Western medicine significantly improved total remission (TR) rate (risk ratios [RR] 1.38, 95% confidence interval [CI] 1.29-1.46, I = 0%, P < 0.00001), complete remission (CR) rate (RR 1.78, 95% CI 1.48-2.15, I = 0, P < 0.00001), partial remission (PR) rate (RR 1.27, 95% CI 1.161.40, I = 0%, P < 0.00001), and serum albumin (ALB) levels (MD: 4.05, 95% CI: 3.02-5.09, I = 91%, P < 0.00001). TCM alone or in combination with Western medicine also reduced proteinuria levels (mean difference [MD]: 1.05, 95% CI: 1.30 to -0.79, I = 95%, P < 0.00001), serum creatinine (SCr) levels (MD: 7.47, 95% CI: 13.70 to -1.24, I = 97%, P = 0.02), and serum antibodies against M-type phospholipase A2 receptor levels (aPLA2Rab) (MD: 19.24, 95% CI: 33.56 to -4.93, I = 87%, P = 0.008). Moreover, the efficacy of combined TCM and Western medicine is superior to that of Western medicine alone in reducing the incidence of infection, hepatotoxicity, and thrombosis. Although the primary and secondary outcomes were consistent, the evidence was generally moderate.
CONCLUSION
The results of this study suggest that TCM alone or in combination with Western medicine may be a feasible alternative therapeutic approach for the treatment of IMN. Nevertheless, additional, rigorously designed, high-quality, and extensive clinical trials are imperative to provide substantial evidence regarding the effectiveness of TCM in managing IMN.
PubMed: 38596093
DOI: 10.1016/j.heliyon.2024.e28836 -
European Journal of Neurology Jul 2024This study was undertaken to provide a comprehensive review of neuroimaging characteristics and corresponding clinical phenotypes of autoimmune glial fibrillary acidic... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study was undertaken to provide a comprehensive review of neuroimaging characteristics and corresponding clinical phenotypes of autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A), a rare but severe neuroinflammatory disorder, to facilitate early diagnosis and appropriate treatment.
METHODS
A PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis)-conforming systematic review and meta-analysis was performed on all available data from January 2016 to June 2023. Clinical and neuroimaging phenotypes were extracted for both adult and paediatric forms.
RESULTS
A total of 93 studies with 681 cases (55% males; median age = 46, range = 1-103 years) were included. Of these, 13 studies with a total of 535 cases were eligible for the meta-analysis. Clinically, GFAP-A was often preceded by a viral prodromal state (45% of cases) and manifested as meningitis, encephalitis, and/or myelitis. The most common symptoms were headache, fever, and movement disturbances. Coexisting autoantibodies (45%) and neoplasms (18%) were relatively frequent. Corticosteroid treatment resulted in partial/complete remission in a majority of cases (83%). Neuroimaging often revealed T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities (74%) as well as perivascular (45%) and/or leptomeningeal (30%) enhancement. Spinal cord abnormalities were also frequent (49%), most commonly manifesting as longitudinally extensive myelitis. There were 88 paediatric cases; they had less prominent neuroimaging findings with lower frequencies of both T2/FLAIR hyperintensities (38%) and contrast enhancement (19%).
CONCLUSIONS
This systematic review and meta-analysis provide high-level evidence for clinical and imaging phenotypes of GFAP-A, which will benefit the identification and clinical workup of suspected cases. Differential diagnostic cues to distinguish GFAP-A from common clinical and imaging mimics are provided as well as suitable magnetic resonance imaging protocol recommendations.
Topics: Humans; Astrocytes; Autoantibodies; Autoimmune Diseases of the Nervous System; Glial Fibrillary Acidic Protein; Neuroimaging; Neuroinflammatory Diseases; Phenotype
PubMed: 38506182
DOI: 10.1111/ene.16284