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Acta Neurologica Belgica Oct 2023Current myasthenia gravis guidelines recommend the use of azathioprine as first-line steroid sparing agent. However, due to its high cost, compliance to azathioprine is... (Review)
Review
Current myasthenia gravis guidelines recommend the use of azathioprine as first-line steroid sparing agent. However, due to its high cost, compliance to azathioprine is low in developing countries. To determine the efficacy and safety of the cheaper methotrexate as an alternative immunosuppressant, Medline/Pubmed, Embase and Cochrane databases and references were searched for clinical trials and observational studies using the search terms: "Myasthenia OR Myasthenia Gravis OR anti AchR antibody positive Myasthenia Gravis OR anti-MuSK antibody Myasthenia Gravis OR MG" AND "Methotrexate". Of 78 possible articles, only 4 were selected using the following eligibility criteria: population: generalized MG patients; intervention: methotrexate; and outcome: effectiveness, steroid sparing efficacy and adverse effects. Two clinical trials and one observational study noted improvement in different MG outcomes in patients given methotrexate. While one randomized controlled clinical trial concluded that methotrexate has no steroid sparing benefit, a single blinded clinical trial established that methotrexate was a better steroid sparing agent than azathioprine starting at 10th month of use. Adverse effects were rare with non-specific pain and elevated transaminases as the most common complaints. Based on available evidence, MTX may be a safe and effective alternative to AZA as steroid sparing agent in developing countries.
Topics: Humans; Methotrexate; Azathioprine; Immunosuppressive Agents; Myasthenia Gravis; Prednisone; Drug-Related Side Effects and Adverse Reactions; Randomized Controlled Trials as Topic; Observational Studies as Topic
PubMed: 36967437
DOI: 10.1007/s13760-023-02242-w -
Pathology International Jul 2022Immunoglobulin G4 (IgG4)-positive marginal zone lymphoma (MZL) is rare and undefined. It is unclear whether IgG4-positive MZLs have as favorable an outcome as MZLs in...
Immunoglobulin G4 (IgG4)-positive marginal zone lymphoma (MZL) is rare and undefined. It is unclear whether IgG4-positive MZLs have as favorable an outcome as MZLs in general. Also, correlation with IgG4-related disease (IgG4-RD) and IgG4-positive MZLs is unknown. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including"IgG4" and "marginal zone lymphoma" from their inception to February 20, 2022. Twenty-two articles, including six observational studies and 24 cases from 16 case reports and case series, were included. Only one study had a comparative group, and the other five were exploratory observational studies. IgG4-positive MZLs commonly occurred in males (83.3%). It primarily involved ocular adnexa (41.7%) and skin (29.2%). Only 29.2% had concurrent IgG4-RD, and no expiration was noted. While most cases were treated with excision, resection, or clinical observation, 21.7% received rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone as a first-line treatment. This systematic review summarizes the current understanding of the characteristics of IgG4-positive MZLs. While there seems to be IgG4-RD-related and de novo IgG4-positive MZLs, future research needs to clearly define MZL with polyclonal IgG4-positive cells and IgG4-producing lymphoma. Further studies are critical to clarifying long-term prognosis and optimal surveillance planning.
Topics: Humans; Immunoglobulin G; Immunoglobulin G4-Related Disease; Lymphoma, B-Cell, Marginal Zone; Male; Prognosis; Rituximab
PubMed: 35678201
DOI: 10.1111/pin.13251 -
Clinical Nephrology Apr 2022The aim of this study was to analyze the clinical features, risk factors, and outcomes of patients with primary nephrotic syndrome (PNS) who developed (PCP).
OBJECTIVE
The aim of this study was to analyze the clinical features, risk factors, and outcomes of patients with primary nephrotic syndrome (PNS) who developed (PCP).
MATERIALS AND METHODS
We systematically reviewed medical records from 18 PNS patients with PCP admitted to our hospital from April 2007 to April 2019. A total of 180 cases were randomly selected as controls from PNS inpatients without infection.
RESULTS
In PCP patients, the mean age at presentation was 48.5 years, mean duration of prednisone treatment was 3.7 months, and mean prednisone dose on admission was 31.3 mg/d. Eight patients (44.4%) had coexisting infections, most often was (4 patients); 11 patients (61.1%) had ICU admission, and 9 patients (50%) had mechanical ventilation. PCP patients had more prednisone, more immunosuppressive therapy, lower CD4+ cell counts and hemoglobin, and higher serum creatinine than those without infections (p < 0.05). All patients survived after treatment.
CONCLUSION
PCP was not unusual in PNS patients, and the most important risk factors were prednisone usage, other immunosuppressive therapy, and a lower CD4+ cell count; however, these patients had a good outcome after sufficient treatment.
Topics: Humans; Nephrotic Syndrome; Pneumonia, Pneumocystis; Prednisone; Respiration, Artificial; Retrospective Studies; Risk Factors
PubMed: 35113013
DOI: 10.5414/CN110679 -
Journal of Plastic, Reconstructive &... Feb 2022Acute rejection remains a vexing problem in vascularized composite allotransplantation (VCA). Available immunosuppressive regimens are successful at minimizing... (Review)
Review
BACKGROUND
Acute rejection remains a vexing problem in vascularized composite allotransplantation (VCA). Available immunosuppressive regimens are successful at minimizing alloimmune response and allowing VCA in humans. However, repeated rejection episodes are common, and systemic side effects of the current standard regimen (Tacrolimus, MMF, Prednisone) are dose limiting. Novel immunomodulatory approaches to improve allograft acceptance and minimize systemic toxicity are continuously explored in preclinical models. We aimed to systematically summarize past and current approaches to help guide future research in this complex field.
METHODS
We conducted a systematic review of manuscripts listed in the MEDLINE and PubMed databases. For inclusion, articles had to primarily investigate the effect of a therapeutic approach on prolonging the survival of a skin-containing preclinical VCA model. Non-VCA studies, human trials, anatomical and feasibility studies, and articles written in a language other than English were excluded. We followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines.
RESULTS
The search retrieved 980 articles of which 112 articles were ultimately included. The majority of investigations used a rat model. An orthotopic hind limb VCA model was used in 53% of the studies. Cell and drug-based approaches were investigated 58 and 52 times, respectively. We provide a comprehensive review of immunomodulatory strategies used in VCA preclinical research over a timeframe of 44 years.
CONCLUSION
We identify a transition from anatomically non-specific to anatomical models mimicking clinical needs. As limb transplants have been most frequently performed, preclinical research focused on using the hind limb model. We also identify a transition from drug-based suppression therapies to cell-based immunomodulation strategies.
Topics: Animals; Graft Rejection; Humans; Immunomodulation; Immunosuppressive Agents; Rats; Skin; Tacrolimus; Vascularized Composite Allotransplantation
PubMed: 34895853
DOI: 10.1016/j.bjps.2021.11.003 -
Lupus Science & Medicine Jan 2022We aimed to conduct a systematic review and meta-analysis of studies on central nervous system (CNS) infections in patients with SLE, in order to describe their clinical... (Meta-Analysis)
Meta-Analysis Review
We aimed to conduct a systematic review and meta-analysis of studies on central nervous system (CNS) infections in patients with SLE, in order to describe their clinical and microbiological characteristics, and outcomes. A systematic search of PubMed/Medline and Embase electronic databases was performed (March 2021) to identify all published studies on CNS infections and their characteristics in patients with SLE. A random-effects model was adopted and findings were reported with 95% CI. Overall, 6 studies involving 17 751 patients with SLE and 209 SLE cases with CNS infection were included in our meta-analysis. The frequency rate of CNS infections in patients with SLE was 0.012 (95% CI: 0.008 to 0.018). Meningitis was the most common clinical syndrome (93.5%, n=109/114, 95% CI: 82.6% to 97.8%) and (35.9%, n=55, 95% CI: 27.2% to 45.7%) and (27.1%, n=43, 95% CI: 14.6% to 44.8%) were the most common causative pathogens. Our patient-pool showed a mean SLE Disease Activity Index (SLEDAI) score of 7.9 (95% CI: 6.1 to 9.6), while 92.4% (n=72/76, 95% CI: 83.0% to 96.8%) of cases were on oral systemic corticosteroids, with a prednisone equivalent mean daily dose of 30.9 mg/day (95% CI: 18.0 to 43.7). Our meta-analysis revealed a mortality rate of 29.0% (95% CI: 15.0% to 48.6%). Clinicians should maintain a high index of suspicion for cryptococcal and tuberculosis (TB) meningitis in patients with SLE with suspected CNS infection, particularly in those with higher SLEDAI and on higher doses of systemic corticosteroids. In conclusion, initiation of empiric antituberculous treatment for patients with SLE who are highly suspected to have CNS TB is warranted while awaiting the results of diagnostic tests. Antifungals might also be potentially useful empirically in patients with SLE who are suspected to have fungal CNS infections. However, with respect to side effects such as toxicity and high cost of antifungals, decision regarding early antifungal therapy should be guided by early and less time-consuming fungal diagnostic tests.
Topics: Central Nervous System Infections; Humans; Lupus Erythematosus, Systemic; Prednisone
PubMed: 34980679
DOI: 10.1136/lupus-2021-000560 -
Dermatitis : Contact, Atopic,...Systemic corticosteroids are commonly used as a short-term management option for inflammatory skin conditions, such as contact dermatitis. The purpose of our systematic...
Systemic corticosteroids are commonly used as a short-term management option for inflammatory skin conditions, such as contact dermatitis. The purpose of our systematic review was to compare presence and degree of patch test reactions with or without different doses of systemic corticosteroid therapy. The relationship between 20, 30, and 40 mg daily doses of prednisone and retained, diminished, and negated reactions was not linear, whereas the reaction ratings for all patches placed with or without corticosteroid therapy revealed trends toward lower intensity reactions while receiving prednisone ( P < 0.0001, χ 2 , for all doses of prednisone). Our review provides insight into directions for future studies that examine the effect of corticosteroids on patch testing.
Topics: Humans; Patch Tests; Prednisone; Adrenal Cortex Hormones; Glucocorticoids; Dermatitis, Contact
PubMed: 36255380
DOI: 10.1097/DER.0000000000000947 -
Lupus Jun 2022Glucocorticoids have been suggested as a potential therapy in refractory obstetric antiphospholipid syndrome (oAPS). Our aims were to describe a cohort of patients with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Glucocorticoids have been suggested as a potential therapy in refractory obstetric antiphospholipid syndrome (oAPS). Our aims were to describe a cohort of patients with oAPS treated with low-dose glucocorticoids and to perform a systematic review and meta-analysis evaluating the effects of additional glucocorticoids on the pregnancy outcomes in oAPS patients.
METHODS
Retrospective study that included 11 women diagnosed with primary antiphospholipid syndrome. The meta-analysis was conducted by fitting random effects models and was checked for heterogeneity.
RESULTS
All women had suffered from early pregnancy losses and two also had a history of fetal deaths. We studied 47 pregnancies that resulted in 32 abortions (68.1%) and 3 fetal deaths (6.4%). Twenty-six pregnancies were under treatment, mainly LDA and LMWH. Low-dose glucocorticoids were indicated in 13 pregnancies (always in association with LDA and LMWH). There was a decrease in pregnancy loss in those patients treated with LDA and LMWH. Treatment with glucocorticoids significantly increased the rate of successful pregnancy (38.5% abortions in treated vs 85.3% abortions in non-treated pregnancies; =0.003). After multivariate GEE analysis, only glucocorticoids remained inversely associated with pregnancy loss (OR=0.157, (CI 0.025-0.968, =0.046)). The meta-analysis showed that glucocorticoids tended to improve the frequency of successful pregnancy (OR= 0.509 (0.252-1.028), =0.06). Three cases of gestational diabetes and one of preeclampsia were observed in our cohort. The meta-analysis, which mostly included studies using high-dose steroids, showed that glucocorticoids increased not only the frequency of preeclampsia and gestational diabetes, but also the rate of pre-term birth.
CONCLUSIONS
The efficacy of low-dose glucocorticoids in addition to the standard therapy in patients with refractory oAPS should be confirmed in well-designed clinical trials. However, high doses of steroids significantly increase the frequency of maternal and fetal morbidities, making their use strongly inadvisable.
Topics: Abortion, Spontaneous; Antiphospholipid Syndrome; Cohort Studies; Diabetes, Gestational; Female; Fetal Death; Glucocorticoids; Heparin, Low-Molecular-Weight; Humans; Lupus Erythematosus, Systemic; Pre-Eclampsia; Prednisone; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Retrospective Studies
PubMed: 35410552
DOI: 10.1177/09612033221091401 -
Cancers Aug 2023Patients with diffuse large B-cell lymphoma (DLBCL) are treated with rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).... (Review)
Review
Consolidative Radiotherapy after Complete Remission following R-CHOP Immunochemotherapy in Stage III-IV Diffuse Large B-Cell Lymphoma Patients: A Systematic Review and Meta-Analysis.
Patients with diffuse large B-cell lymphoma (DLBCL) are treated with rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). The role of consolidative radiation therapy (RT) remains unclear among patients with advanced DLBCL who achieved complete remission (CR) after R-CHOP immunochemotherapy. The current systematic review and meta-analysis aimed to clarify the role of consolidative RT among these patients. The MEDLINE, Embase, and Cochrane Library databases were searched for studies comparing RT to no RT following CR after R-CHOP immunochemotherapy in Ann Arbor stage III-IV DLBCL patients. Overall survival (OS) was the primary endpoint, and disease-free survival (DFS) was the secondary endpoint. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the primary and secondary outcomes. Review Manager (version 5.4) was used to analyze the data. Six retrospective studies involving 813 patients who received R-CHOP ± consolidative RT were identified. OS was higher in the consolidative RT group, with an HR of 2.01 and a 95% CI of 1.30 to 3.12 ( = 0.002). DFS was also higher in the RT group, with an HR of 2.18 and a 95% CI of 1.47 to 3.24 ( < 0.0001). The results suggested that consolidative RT improved OS and DFS compared to no RT among advanced-stage DLBCL patients. Further research is needed to determine the optimal radiation fields and the appropriate indications for consolidative RT for advanced-stage DLBCL patients in the rituximab era.
PubMed: 37568756
DOI: 10.3390/cancers15153940 -
Medicine Apr 2020Rituximab (RTX) is considered to be a promising drug for curing membranous nephropathy. However, the efficacy and safety of RTX in treating membranous nephropathy remain... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND AND OBJECTIVES
Rituximab (RTX) is considered to be a promising drug for curing membranous nephropathy. However, the efficacy and safety of RTX in treating membranous nephropathy remain uncertain. This meta-analysis aimed to investigate the efficacy and safety of RTX in patients with membranous nephropathy.
METHODS
A literature search was performed using Pubmed, Embase, OVID, and Cochrane Library and randomized controlled trials (RCTs) case-controls and cohort studies published till 30 July 2019 were assessed. The studies assessing the efficacy and safety of RTX in patients with membranous nephropathy were included.
RESULTS
Eight relevant trials involving 542 patients were included in the meta-analysis. It was found that RTX did not significantly improve serum albumin levels and e-GFR when compared with the control group (including cyclosporine and cyclophosphamide, chlorambucil, prednisone, non-immunosuppressive anti-proteinuria treatment), serum albumin levels (OR = 0.31, 95%CI-0.12-0.74, P = .15), e-GFR (OR = -1.49, 95%CI-17.14-14.17, P = .85). However, RTX did reduce the serum creatinine (OR = -0.01, 95%CI-0.36-0.34, P = .95) and urinary protein (OR = -2.39, 95%CI -7.30 -2.53, P = .34) levels. Also, in comparison to the control group, RTX did improve the total remission rate (OR = 1.63, 95%CI 0.48-5.54, P = .43), achieve a higher rate of complete remission (OR = 2.54, 95%CI 1.65-3.90, P < .01) and also reduced the amount of M-type phospholipase A2 receptor-Antibody depletion in patients (OR = 5.59, 95%CI 1.81-17.2, P = .003). RTX-related adverse events were mostly mild (most infusion-related reactions) in nature and serious adverse events were rare.
CONCLUSION
RTX proved to be efficient, well-tolerated and a safe drug in the treatment of membranous nephropathy. Most patients reach complete remission during the follow-up period, and relapse is rare. RTX may turn out to be promising in membranous nephropathy patients.
Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Case-Control Studies; Chlorambucil; Cyclophosphamide; Cyclosporine; Female; Glomerular Filtration Rate; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Male; Middle Aged; Prednisone; Proteinuria; Randomized Controlled Trials as Topic; Receptors, Phospholipase A2; Remission Induction; Rituximab; Safety; Serum Albumin; Treatment Outcome
PubMed: 32311997
DOI: 10.1097/MD.0000000000019804 -
Future Oncology (London, England) Feb 2022To understand the burden of treatment-naive peripheral T-cell lymphoma (PTCL). A systematic literature review was conducted in November 2020 following best practice...
To understand the burden of treatment-naive peripheral T-cell lymphoma (PTCL). A systematic literature review was conducted in November 2020 following best practice methodology. Fifty-five clinical studies were included, mostly investigating cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) or 'CHOP-like' regimens, with combination regimens showing similar effectiveness to CHOP alone. Aside from the combination of brentuximab vedotin + cyclophosphamide, doxorubicin and prednisone (A+CHP), other available treatments showed no statistically significant benefit over CHOP in terms of overall or progression-free survival in overall PTCL patients. The mean monthly cost per patient in the USA ranged from 6328 to US$9356 based on six studies. One economic evaluation demonstrated A+CHP to be a more cost-effective treatment option than CHOP. Further research is needed to understand the humanistic and cost impact of frontline treatment for PTCL and its specific subtypes.
Topics: Antineoplastic Combined Chemotherapy Protocols; Brentuximab Vedotin; Cost of Illness; Cyclophosphamide; Doxorubicin; Female; Humans; Lymphoma, T-Cell, Peripheral; Male; Prednisone; Treatment Outcome; Vincristine
PubMed: 34851173
DOI: 10.2217/fon-2021-1032