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ACR Open Rheumatology May 2022The objective of this study was to compare the efficacy and safety of two rituximab (RTX) regimens for the induction of remission in severe antineutrophil cytoplasm...
OBJECTIVE
The objective of this study was to compare the efficacy and safety of two rituximab (RTX) regimens for the induction of remission in severe antineutrophil cytoplasm antibody-associated vasculitis (AAV): the four-dose (375 mg/m intravenously weekly) versus the two-dose (1000 mg intravenously biweekly) regimen.
METHODS
A systematic review was performed to identify studies using the four- and/or two-dose RTX regimens for induction of remission in severe AAV. Disease status 6 months after RTX infusion was required for inclusion. Patients were excluded if they received concomitant cyclophosphamide or plasma exchange. The primary end point was the proportion of patients in complete remission at 6 months. The pooled estimate was obtained by using meta-analysis methods for proportions with random effects. Secondary end points included antineutrophil cytoplasm antibody status, number of patients with B-cell depletion, mean prednisone dose, infections, and death.
RESULTS
A total of 27 studies and 506 patients were included for analysis: 361 patients received the four-dose regimen, and 145 patients received the two-dose regimen. Most patients had relapsing disease at inclusion (83% and 92% of patients, respectively). There was no significant difference between the four- and two-dose regimens, with a complete remission achieved in 85% (95% confidence interval [CI]: 70-96) and 91% (95% CI: 79-99) of patients, respectively. At 6 months, both regimens were associated with a similar mean daily prednisone dose (8.1 mg), infections (12% in both), and death (1% vs. 0%, respectively).
CONCLUSION
No difference was found in terms of efficacy or safety between the four- and two-dose RTX regimens for induction of remission in severe AAV. https://onlinelibrary.wiley.com/doi/10.1002/acr2.11274 Bénard V, Farhat C, Zarandi-Nowroozi M, Durand M, Charles P, Puéchal X, et al. Comparison of two rituximab induction regimens for antineutrophil cytoplasm antibody-associated vasculitis: systematic review and meta-analysis. ACR Open Rheumatol 2021;3:484-94.
PubMed: 35119219
DOI: 10.1002/acr2.11409 -
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 -
Clinical Neurology and Neurosurgery Feb 2022Recent studies suggest that the clinical course and outcomes of patients with coronavirus disease 2019 (COVID-19) and myasthenia gravis (MG) are highly variable. We...
OBJECTIVE
Recent studies suggest that the clinical course and outcomes of patients with coronavirus disease 2019 (COVID-19) and myasthenia gravis (MG) are highly variable. We performed a systematic review of the relevant literature with a key aim to assess the outcomes of invasive ventilation, mortality, and hospital length of stay (HLoS) for patients presenting with MG and COVID-19.
METHODS
We searched the PubMed, Scopus, Web of Science, and MedRxiv databases for original articles that reported patients with MG and COVID-19. We included all clinical studies that reported MG in patients with confirmed COVID-19 cases via RT-PCR tests. We collected data on patient background characteristics, symptoms, time between MG and COVID-19 diagnosis, MG and COVID-19 treatments, HLoS, and mortality at last available follow-up. We reported summary statistics as counts and percentages or mean±SD. When necessary, inverse variance weighting was used to aggregate patient-level data and summary statistics.
RESULTS
Nineteen studies with 152 patients (mean age 54.4 ± 12.7 years; 79/152 [52.0%] female) were included. Hypertension (62/141, 44.0%) and diabetes (30/141, 21.3%) were the most common comorbidities. The mean time between the diagnosis of MG and COVID-19 was7.0 ± 6.3 years. Diagnosis of COVID-19 was confirmed in all patients via RT-PCR tests. Fever (40/59, 67.8%) and ptosis (9/55, 16.4%) were the most frequent COVID-19 and MG symptoms, respectively. Azithromycin and ceftriaxone were the most common COVID-19 treatments, while prednisone and intravenous immunoglobulin were the most common MG treatments. Invasive ventilation treatment was required for 25/59 (42.4%) of patients. The mean HLoS was 18.2 ± 9.9 days. The mortality rate was 18/152 (11.8%).
CONCLUSION
This report provides an overview of the characteristics, treatment, and outcomes of MG in COVID-19 patients. Although COVID-19 may exaggerate the neurological symptoms and worsens the outcome in MG patients, we did not find enough evidence to support this notion. Further studies with larger numbers of patients with MG and COVID-19 are needed to better assess the clinical outcomes in these patients.
Topics: Adolescent; Adult; COVID-19; Child; Female; Hospitalization; Humans; Male; Middle Aged; Myasthenia Gravis; Respiration, Artificial; Survival Rate; Young Adult
PubMed: 35091255
DOI: 10.1016/j.clineuro.2022.107140 -
Journal of Cancer Research and Clinical... Apr 2022Smoldering multiple myeloma (SMM) is an intermediate pre-malignant condition with individuals having a distinct risk of progression to overt myeloma. The optimal... (Review)
Review
The effect of intervention versus watchful waiting on disease progression and overall survival in smoldering multiple myeloma: a systematic review of randomized controlled trials.
BACKGROUND
Smoldering multiple myeloma (SMM) is an intermediate pre-malignant condition with individuals having a distinct risk of progression to overt myeloma. The optimal management option has remained controversial due to the heterogeneous nature of the condition in which progression to overt diseases is variable. The question of who, when, and what to use for the treatment of SMM remains equivocal. We performed a systematic review of randomized controlled trials and summarized the current evidence supporting the best approach to the management of SMM.
METHODS
A comprehensive literature search of Medline/PubMed, PubMed Central, Embase, Scopus, Web of Science, Wiley Cochrane Library, CINAHL, clinicaltrial.gov, and conference proceedings of ASCO, ASH, EHA, and ESMO was performed on October 25, 2020. Synthesis of the result was done using narrative analysis.
RESULT
Of the total 1560 identified records, 10 eligible studies involving 1157 patients made up of 580 in the intervention group and 577 in the control group were included in this review. Three early trials of melphalan and prednisone fail to demonstrate any significant impact on disease progression with major toxicities reported. Three trials on bisphosphonate monotherapy show reduced skeletal-related events without any clinical effect on disease progression. Lenalidomide monotherapy or as part of a combination therapy demonstrates superiority in delaying disease progression over observation. Only Lenalidomide and dexamethasone combination demonstrated superior overall survival over observation across the trials.
CONCLUSION
Trials of lenalidomide in a less intensive approach has shown promise in delaying disease progression and should be investigated further in clinical trials.
Topics: Disease Progression; Humans; Lenalidomide; Randomized Controlled Trials as Topic; Smoldering Multiple Myeloma; Watchful Waiting
PubMed: 35059867
DOI: 10.1007/s00432-022-03920-7 -
Integrative Medicine Research Jun 2022Myasthenia Gravis (MG) is a disorder of neuromuscular transmission bringing mild ocular weakness to severe generalized muscle weakness and disability. The conventional... (Review)
Review
BACKGROUND
Myasthenia Gravis (MG) is a disorder of neuromuscular transmission bringing mild ocular weakness to severe generalized muscle weakness and disability. The conventional treatments have long-term side effects, and Chinese herbal medicines (CHM) have shown possible effect and safety for MG patients, but the existing evidence was not robust enough and the results were out of date.
METHODS
Searching for randomized controlled trials (RCTs) was conducted in 7 databases and clinical trial registries until July 2021. The ROB 2 tool was used to assess the study quality and GRADE was used to assess the quality of whole evidence. Meta-analyses were conducted and the results were presented as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI).
RESULTS
Nineteen RCTs (1283 participants) testing 13 kinds of CHM with adequate randomization were included and six RCTs investigating Compound Huangqi were included in the meta-analyses. In addition to conventional treatment, nine CHMs reduced symptom scores of MG. Compound Huangqi plus conventional treatment (pyridostigmine bromide or prednisone or both) reduced the symptom scores compared with conventional treatment (MD = -3.56, 95%CI -4.86 to -2.26). Less adverse events happened in the CHM groups (3/247 in the CHM groups, 52/245 in the control groups, RR = 0.13, 95%CI 0.06 to 0.30, 9 RCTs, a total of 492 participants). The effect on quality of life was inconsistent.
CONCLUSION
Nine CHMs could probably bring benefit for MG symptom improvement. Moderate to low certainty of evidence supported Compound Huangqi added-on conventional treatment probably bring extra benefit of improving MG symptoms. Adding CHMs could be safer than giving only conventional treatment.
STUDY REGISTRATION
The protocol was registered in PROSPERO (ID: 32718).
PubMed: 35024335
DOI: 10.1016/j.imr.2021.100806 -
Blood Cancer Journal Jan 2022Front-line treatment for follicular lymphoma has evolved with the introduction of maintenance therapy, bendamustine (Benda), obinutuzumab (G), and lenalidomide (Len). We... (Meta-Analysis)
Meta-Analysis
Front-line treatment for follicular lymphoma has evolved with the introduction of maintenance therapy, bendamustine (Benda), obinutuzumab (G), and lenalidomide (Len). We conducted a random-effects Bayesian network meta-analysis (NMA) of phase 3 randomized controlled trials (RCTs) to identify the regimens with superior efficacy. Progression-free survival (PFS) was compared between 11 modern regimens with different immunochemotherapy and maintenance strategies. G-Benda-G resulted in with the best PFS, with an HR of 0.41 compared to R-Benda, a surface under the cumulative ranking curve (SUCRA) of 0.97, a probability of being the best treatment (PbBT) of 72%, and a posterior ranking distribution (PoRa) of 1 (95% BCI 1-3). This was followed by R-Benda-R4 (HR = 0.49, PbBT = 25%, PoRa = 2) and R-Benda-R (HR = 0.60, PbBT = 3%, PoRa = 3). R-CHOP-R (HR = 0.96) and R-Len-R (HR = 0.97) had similar efficacy to R-Benda. Bendamustine was a better chemotherapy backbone than CHOP either with maintenance (R-Benda-R vs R-CHOP-R, HR = 0.62; G-Benda-G vs G-CHOP-G, HR = 0.55) or without maintenance therapy (R-Benda vs R-CHOP, HR = 0.68). Rituximab maintenance improved PFS following R-CHOP (R-CHOP-R vs R-CHOP, HR = 0.65) or R-Benda (R-Benda-R vs R-Benda, HR = 0.60; R-Benda-R4 vs R-Benda, HR = 0.49). In the absence of multi-arm RCTs that include all common regimens, this NMA provides an important and useful guide to inform treatment decisions.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Cyclophosphamide; Doxorubicin; Humans; Immunotherapy; Lymphoma, Follicular; Maintenance Chemotherapy; Prednisone; Progression-Free Survival; Randomized Controlled Trials as Topic; Rituximab; Treatment Outcome; Vincristine
PubMed: 34987165
DOI: 10.1038/s41408-021-00598-x -
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 -
Translational Pediatrics Nov 2021Hormonal drug therapy has been widely used in clinical practice for the treatment of progressive muscular dystrophy (PMD). Glucocorticoids, as a common drug in the...
BACKGROUND
Hormonal drug therapy has been widely used in clinical practice for the treatment of progressive muscular dystrophy (PMD). Glucocorticoids, as a common drug in the clinical treatment of PMD, have been reported in several clinical studies.
METHODS
Chinese and English databases were respectively searched using "randomized controlled trials", "Duchenne-type myotonic dystrophy", "glucocorticoids", Prednisone", "Prednisolone", and "Methylprednisolone", and "Defibrotide" were used as search terms. The meta-analysis was performed using the RevMan 5.3 and Stata 13 software provided by the Cochrane system.
RESULTS
this study included five randomized controlled trials, all of which described the correct randomization method. There were four detailed descriptions of hidden distribution schemes. There were four literatures using blind method. Heterogeneity analysis showed that there was some heterogeneity between the results of the mean prognostic muscle strength, walking time of 9 meters, and 4 flights of stairs climbing between the glucocorticoid-treated group (the experimental group) and the placebo group (the control group). There were no significant differences between the experimental group and the control group in average muscle strength level, walking time of 9 meters and climbing time of 4 flights of stairs (MD =1.77; 95% CI: -0.95 to 4.48; P=0.20>0.05), (MD =-12.27; 95% CI: -35.94 to 11.40; P=0.31>0.01), (MD =-3.09; 95% CI: -11.16 to 4.99; P=0.45>0.05). In addition, glucocorticoid treatment significantly increased creatine kinase level in patients with PMD (MD =-0.28, 95% CI: -0.57 to 0.00; P=0.05). In terms of the incidence of adverse reactions, glucocorticoid treatment significantly increased the prognostic probability of acne, rapid hair growth, and emotional irritability in PMD patients (OR =2.40; 95% CI: 1.09 to 5.27; P=0.03<0.05), (OR =3.05; 95% CI: 1.55 to 5.99; P=0.001<0.05), (OR =4.04; 95% CI: 1.82 to 10.63; P=0.001<0.05). There was no significant difference in the incidence of prognostic depression between the experimental group and the control group (OR =5.11; 95% CI: 0.80 to 32.79; P=0.09>0.05).
DISCUSSION
The results suggest that glucocorticoids have a significant effect on PMD patients, but to a certain extent they increase the incidence of adverse reactions in patients after treatment. However, due to the lack of complete clinical data in some ongoing studies, our conclusions may not be fully representative.
PubMed: 34976770
DOI: 10.21037/tp-21-461 -
Computational and Mathematical Methods... 2021Investigate the optimum time of acupuncture treatment in peripheral facial paralysis in order to provide evidence for clinical treatment. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Investigate the optimum time of acupuncture treatment in peripheral facial paralysis in order to provide evidence for clinical treatment.
METHODS
CNKI, Wanfang, PubMed, Cochrane Library, and EMBASE databases were systematically searched from the inception dates to February 20, 2020. Studies limited to participants with acute peripheral facial paralysis treated with acupuncture and patients without information of the stage were excluded. The primary outcomes were effective rate and cure rate (based on facial nerve function scores). This meta-analysis is registered with PROSPERO, number CRD42020169870.
RESULTS
15 randomized controlled trials that enrolled 2847 participants met the selection criteria. There was no significant differences in the effective rate (RR, 1.22; 95% CI, 0.70-2.11) when comparing acupuncture to prednisone therapy in acute facial paralysis. Acupuncture treatment in the acute stage increased both the effective rate (RR, 1.03; 95% CI, 1.00-1.07) and the cure rate (RR, 1.34; 95% CI, 1.14-1.58) compared to that in the nonacute stage.
CONCLUSIONS
In this meta-analysis, acupuncture showed a better effect in the acute stage than the nonacute stage for participants with peripheral facial paralysis. There was no statistical difference in the effective rate no matter the choice of acupuncture or prednisone therapies in the acute stage. These findings encourage early acupuncture treatment in peripheral facial paralysis.
Topics: Acupuncture Therapy; Acute Disease; China; Computational Biology; Facial Nerve; Facial Paralysis; Humans; Secondary Prevention; Time Factors; Treatment Outcome
PubMed: 34956397
DOI: 10.1155/2021/4221955 -
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