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Biomedicines Sep 2023The clinical response to classical immunosuppressant drugs (cIMDs) is highly variable among individuals. We performed a systematic review of published evidence... (Review)
Review
The clinical response to classical immunosuppressant drugs (cIMDs) is highly variable among individuals. We performed a systematic review of published evidence supporting the hypothesis that gut microorganisms may contribute to this variability by affecting cIMD pharmacokinetics, efficacy or tolerability. The evidence that these drugs affect the composition of intestinal microbiota was also reviewed. The PubMed and Scopus databases were searched using specific keywords without limits of species (human or animal) or time from publication. One thousand and fifty five published papers were retrieved in the initial database search. After screening, 50 papers were selected to be reviewed. Potential effects on cIMD pharmacokinetics, efficacy or tolerability were observed in 17/20 papers evaluating this issue, in particular with tacrolimus, cyclosporine, mycophenolic acid and corticosteroids, whereas evidence was missing for everolimus and sirolimus. Only one of the papers investigating the effect of cIMDs on the gut microbiota reported negative results while all the others showed significant changes in the relative abundance of specific intestinal bacteria. However, no unique pattern of microbiota modification was observed across the different studies. In conclusion, the available evidence supports the hypothesis that intestinal microbiota could contribute to the variability in the response to some cIMDs, whereas data are still missing for others.
PubMed: 37761003
DOI: 10.3390/biomedicines11092562 -
International Urology and Nephrology Apr 2024Tubulointerstitial nephritis and uveitis (TINU) syndrome is an uncommon disease. We present a confirmed case of TINU syndrome, and a systematic review of epidemiological...
PURPOSE
Tubulointerstitial nephritis and uveitis (TINU) syndrome is an uncommon disease. We present a confirmed case of TINU syndrome, and a systematic review of epidemiological characteristics, clinical manifestations, management, and outcomes in Chinese patients.
METHODS
A systematic search was carried out using defined terms and updated up to September 2022, in PubMed, Web of Science, Wanfang, CNKI, and VIP, to identify reported cases of TINU in China, according to PRISMA guidelines.
RESULTS
An 18-year-old boy presented with elevated serum creatinine and 24-h urine protein level of > 2 g. Inspection result revealed acute tubulointerstitial nephritis, and bilateral uveitis. The patient was diagnosed with TINU syndrome and received treatment with methylprednisolone sodium succinate, which resulted in a significant decrease in creatinine and urinary protein levels. Systematic review identified 35 publications that met the inclusion criteria. A total of 71 cases were included in this article, of which 70 were from publications and 1 was from our hospital. The median age at onset was 42 years and was significantly lower in males than females (P < 0.05). The symptoms of uveitis often occurred after kidney injury (54%) and most uveitis was anterior (55%) and bilateral (75%). Among the 51 patients who were followed up for more than 6 months, 24 had recurrent ocular symptoms or progression to chronic uveitis. Twenty patients experienced chronic or progressive kidney disease.
CONCLUSION
TINU syndrome is prone to misdiagnosis because kidney damage may not occur simultaneously with uveitis. The incidence of kidney sequelae in children is lower than that in adults, and glucocorticoids are the preferred treatment.
INPLASY REGISTRATION NUMBER
INPLASY202350050.
Topics: Adolescent; Adult; Female; Humans; Male; China; Glucocorticoids; Nephritis, Interstitial; Uveitis
PubMed: 37755610
DOI: 10.1007/s11255-023-03797-6 -
Frontiers in Neurology 2023Acute Necrotizing Encephalopathy (ANE) is a condition characterized by symmetric, bilateral lesions affecting the thalamus and potentially other areas of the brain...
Acute Necrotizing Encephalopathy (ANE) is a condition characterized by symmetric, bilateral lesions affecting the thalamus and potentially other areas of the brain following an acute febrile illness. It manifests clinically as abrupt development of encephalopathy, or alteration in mental status that often includes development of seizures and progression to coma. Treatment strategies combine immunosuppressive therapies and supportive care with varying levels of recovery, however there are no universally accepted, data-driven, treatment algorithms for ANE. We first report a case of a previously healthy 10-year-old female with acute onset diplopia, visual hallucinations, lethargy, and seizures in the setting of subacute non-specific viral symptoms and found to have bilateral thalamic and brainstem lesions on MRI consistent with ANE. She was treated with a combination of immunomodulatory therapies and ultimately had a good outcome. Next, we present a meta-analysis of 10 articles with a total of 158 patients meeting clinical and radiographic criteria for ANE. Each article reported immunosuppressive treatments received, and associated morbidity or mortality outcome for each individual patient. Through our analysis, we confirm the effectiveness of high-dose, intravenous, methylprednisolone (HD-IV-MP) therapy implemented early in the disease course (initiation within 24 h of neurologic symptom onset). There was no significant difference between patients treated with and without intravenous immunoglobulin (IVIG). There was no benefit of combining IVIG with early HD-IV-MP. There is weak evidence suggesting a benefit of IL-6 inhibitor tocilizumab, especially when used in combination with early HD-IV-MP, though this analysis was limited by sample size. Finally, plasma exchange (PLEX) improved survival. We hope this meta-analysis will be useful for clinicians making treatment decisions for patients with this potentially devastating condition.
PubMed: 37745654
DOI: 10.3389/fneur.2023.1239746 -
Current Rheumatology Reviews 2024Henoch-Schönlein purpura (IgA vasculitis) is the most common childhood vasculitis, one of its complications is renal involvement. However, several treatment regimens...
BACKGROUNDS
Henoch-Schönlein purpura (IgA vasculitis) is the most common childhood vasculitis, one of its complications is renal involvement. However, several treatment regimens have been proposed to improve renal function in the long term, but which drug regimen can be most effective is still controversial.
METHODS
This study was a systematic review. In order to find evidence related to the purpose of this study, databases including Google Scholar, Web of Science, ProQuest and Medline via PubMed, and Scopus were searched with the appropriate keywords. QUADAS-2 (a Quality Assessment tools for Diagnostic Accuracy Studies) checklist was also used to evaluate the quality of studies. Based on the keywords used in reviewing the information sources of scientific articles, in the first stage, 86 studies were included in the review. Taking into account characteristics such as lack of homogeneity with the objectives of the present study, finally, 11 studies were selected for analysis and final evaluation.
RESULTS
A total of 11 studies, including 722 patients in the age range of 5.5 to 9.9 years with HSP were included in the study. The follow-up period of the patients varied from 6 months to 16 years in terms of examining the treatment process. In terms of study type, 7 studies were conducted as prospective or retrospective (non-interventional) cohorts and 4 studies as randomized clinical trials. The treatment regimen of injectable methylprednisolone followed by oral prednisolone resulted in a long-term recovery of 79.2% (95% confidence interval between 0.66% and 88.2%); however, the need for additional immunosuppressive in two studies was mentioned as 38% and 46.1%, respectively. In the therapeutic regimen of oral methylprednisolone alone, a significant improvement in long-term renal function was achieved in comparison with placebo. Administration of injectable methylprednisolone followed by cyclosporine A had the highest effectiveness in terms of improving renal function in the long term.
CONCLUSION
Regimes based on the administration of prednisolone (either oral or injectable, either as a single drug or as a combination) lead to long-term improvement of renal function in patients with HSP, but the use of other immunosuppressive drugs such as cyclosporine A, of course, with optimizing the drug dose can lead to a significant improvement in the clinical performance.
Topics: Humans; Child; Child, Preschool; Kidney; IgA Vasculitis; Cyclosporine; Retrospective Studies; Prospective Studies; Immunosuppressive Agents; Methylprednisolone
PubMed: 37698064
DOI: 10.2174/1573397119666230825163008 -
Journal of Neurology Nov 2023Acute necrotizing encephalopathy (ANE) is a rare neurological complication related to COVID-19. Here we present a case series of six Chinese cases with ANE associated... (Review)
Review
Acute necrotizing encephalopathy (ANE) is a rare neurological complication related to COVID-19. Here we present a case series of six Chinese cases with ANE associated with COVID-19 and review all reported cases in the literature. A total of six cases with ANE related to COVID-19 were enrolled in this study. Clinical manifestations, neuroimaging data, treatment and outcomes of these patients were analyzed. A literature review was performed in Pubmed and Embase and 25 cases with clinical and neuroimaging data were collected and analyzed. Among our six cases, the age of onset ranged from 15 to 56 years, with a male-to-female ratio of nearly 1:1. All patients presented with reduced consciousness. Elevated interleukin 6 in serum and/or cerebrospinal fluid (CSF) was detected in four patients. Two patients improved clinically after intravenous methylprednisolone and intravenous immunoglobulin (IVIG). Based on the literature review, the majority of cases were from Europe and the United States (60%). Two age peaks at 10-20 years (20%) and 50-60 years (28%) were observed. Two cases were found with a heterozygous Thr585Met mutation. The mortality of ANE caused by COVID-19 was 42%. The use of IVIG in combination with other immunotherapies was related to better outcome (P = 0.041) and both two patients who received Tocilizumab survived. This is the first Chinese case series about ANE associated with COVID-19. Elevated serum and CSF interlukin-6 were found in certain cases. The mortality and morbidity rates remained high although prompt immunotherapy could improve the outcomes.
PubMed: 37695531
DOI: 10.1007/s00415-023-11915-8 -
Medicine Sep 2023Methylprednisolone (MP) and dexamethasone (DXM) are commonly prescribed hormone drugs for treating coronavirus pandemic disease 2019 (COVID-19) patients, but conflicting... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Methylprednisolone (MP) and dexamethasone (DXM) are commonly prescribed hormone drugs for treating coronavirus pandemic disease 2019 (COVID-19) patients, but conflicting results from previous studies and meta-analyses on their efficacy and safety necessitate further investigation. Therefore, in this study, we conducted a systematic review and meta-analysis of randomized controlled trials to enhance the level of evidence and compare the efficacy and safety of MP and DXM in COVID-19 patients.
METHODS
We conducted a comprehensive search of PubMed, Web of Science, Embase, and Cochrane Library databases to retrieve randomized clinical trials. Our primary outcome measure was all-cause mortality, with secondary outcomes including admission to the intensive care unit, length of hospital stay, mechanical ventilation, and adverse events.
RESULTS
This study analyzed six randomized controlled trials involving 1403 patients (MP group: 704; DXM group: 699). The results of the analysis showed no significant differences in mortality rates, admission to intensive care units, hospitalization time, mechanical ventilation, or adverse events between the MP and DXM groups (P > .05). However, a significant difference was observed in the incidence of hyperglycemia between these 2 groups (RR = 1.78, 95% CI [1.09, 2.89], P = .02, I2 = 78%).
CONCLUSION
The results of this meta-analysis showed that there was no difference in mortality, ICU admission rate, hospital stay, mechanical ventilation, or adverse events between MP and DXM in the treatment of COVID-19. The incidence of hyperglycemia with methylprednisolone was higher than that with dexamethasone.
Topics: Humans; COVID-19; COVID-19 Drug Treatment; Randomized Controlled Trials as Topic; Hyperglycemia; Methylprednisolone; Dexamethasone
PubMed: 37682199
DOI: 10.1097/MD.0000000000034738 -
Global Epidemiology Dec 2023COVID-19 is associated with severe pneumonia lung damage, acute respiratory distress syndrome (ARDS), and mortality. In this study, we aimed to compare corticosteroids'... (Review)
Review
BACKGROUND
COVID-19 is associated with severe pneumonia lung damage, acute respiratory distress syndrome (ARDS), and mortality. In this study, we aimed to compare corticosteroids' effect on the mortality risk in patients hospitalized with COVID-19.
METHODS
PubMed, Web of Science, Scopus, Cochrane Library, and Embase, were searched using a predesigned search strategy. Randomized controlled trials (RCTs) that had compared the corticosteroid drugs were included. The hazard ratio (HR) with a 95% confidence interval (CI) was used to summarize the effect size from the network meta-analysis (NMA).
RESULTS
Out of 329 retrieved references, 12 RCTs with 11,455 participants met the eligibility criteria in this review. The included RCTs formed one network with six treatments. In addition, five treatments in two RCTs were not connected to the network. Methylprednisolone + usual care (UC) versus UC decreased the risk of death by 0.65 (95% CI: 0.47, 0.90). Among treatments in the network the highest P-score (0.89) was related to Methylprednisolone + UC.
CONCLUSION
Based on the results of this NMA it seems Methylprednisolone + UC to be the best treatment option in patients with COVID-ARDS and COVID pneumonia.
PubMed: 37637717
DOI: 10.1016/j.gloepi.2023.100116 -
The Cochrane Database of Systematic... Aug 2023Bullous pemphigoid (BP) is the most common autoimmune blistering disease. Oral steroids are the standard treatment. We have updated this review, which was first... (Review)
Review
BACKGROUND
Bullous pemphigoid (BP) is the most common autoimmune blistering disease. Oral steroids are the standard treatment. We have updated this review, which was first published in 2002, because several new treatments have since been tried.
OBJECTIVES
To assess the effects of treatments for bullous pemphigoid.
SEARCH METHODS
We updated searches of the following databases to November 2021: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We searched five trial databases to January 2022, and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs).
SELECTION CRITERIA
RCTs of treatments for immunofluorescence-confirmed bullous pemphigoid.
DATA COLLECTION AND ANALYSIS
At least two review authors, working independently, evaluated the studies against the review's inclusion criteria and extracted data from included studies. Using GRADE methodology, we assessed the certainty of the evidence for each outcome in each comparison. Our primary outcomes were healing of skin lesions and mortality.
MAIN RESULTS
We identified 14 RCTs (1442 participants). The main treatment modalities assessed were oral steroids, topical steroids, and the oral anti-inflammatory antibiotic doxycycline. Most studies reported mortality but adverse events and quality of life were not well reported. We decided to look at the primary outcomes 'disease control' and 'mortality'. Almost all studies investigated different comparisons; two studies were placebo-controlled. The results are therefore based on a single study for each comparison except azathioprine. Most studies involved only small numbers of participants. We assessed the risk of bias for all key outcomes as having 'some concerns' or high risk, due to missing data, inappropriate analysis, or insufficient information. Clobetasol propionate cream versus oral prednisone Compared to oral prednisone, clobetasol propionate cream applied over the whole body probably increases skin healing at day 21 (risk ratio (RR 1.08, 95% confidence interval (CI) 1.03 to 1.13; 1 study, 341 participants; moderate-certainty evidence). Skin healing at 21 days was seen in 99.8% of participants assigned to clobetasol and 92.4% of participants assigned to prednisone. Clobetasol propionate cream applied over the whole body compared to oral prednisone may reduce mortality at one year (RR 0.73, 95% CI 0.53 to 1.01; 1 study, 341 participants; low-certainty evidence). Death occurred in 26.5% (45/170) of participants assigned to clobetasol and 36.3% (62/171) of participants assigned to oral prednisone. This study did not measure quality of life. Clobetasol propionate cream may reduce risk of severe complications by day 21 compared with oral prednisone (RR 0.65, 95% CI 0.50 to 0.86; 1 study, 341 participants; low-certainty evidence). Mild clobetasol propionate cream regimen (10 to 30 g/day) versus standard clobetasol propionate cream regimen (40 g/day) A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen probably does not change skin healing at day 21 (RR 1.00, 95% CI 0.97 to 1.03; 1 study, 312 participants; moderate-certainty evidence). Both groups showed complete healing of lesions at day 21 in 98% participants. A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen may not change mortality at one year (RR 1.00, 95% CI 0.75 to 1.32; 1 study, 312 participants; low-certainty evidence), which occurred in 118/312 (37.9%) participants. This study did not measure quality of life. A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen may not change adverse events at one year (RR 0.94, 95% CI 0.78 to 1.14; 1 study, 309 participants; low-certainty evidence). Doxycycline versus prednisolone Compared to prednisolone (0.5 mg/kg/day), doxycycline (200 mg/day) induces less skin healing at six weeks (RR 0.81, 95% CI 0.72 to 0.92; 1 study, 213 participants; high-certainty evidence). Complete skin healing was reported in 73.8% of participants assigned to doxycycline and 91.1% assigned to prednisolone. Doxycycline compared to prednisolone probably decreases mortality at one year (RR 0.25, 95% CI 0.07 to 0.89; number needed to treat for an additional beneficial outcome (NNTB) = 14; 1 study, 234 participants; moderate-certainty evidence). Mortality occurred in 2.4% (3/132) of participants with doxycycline and 9.7% (11/121) with prednisolone. Compared to prednisolone, doxycycline improved quality of life at one year (mean difference 1.8 points lower, which is more favourable on the Dermatology Life Quality Index, 95% CI 1.02 to 2.58 lower; 1 study, 234 participants; high-certainty evidence). Doxycycline compared to prednisolone probably reduces severe or life-threatening treatment-related adverse events at one year (RR 0.59, 95% CI 0.35 to 0.99; 1 study, 234 participants; moderate-certainty evidence). Prednisone plus azathioprine versus prednisone It is unclear whether azathioprine plus prednisone compared to prednisone alone affects skin healing or mortality because there was only very low-certainty evidence from two trials (98 participants). These studies did not measure quality of life. Adverse events were reported in a total of 20/48 (42%) participants assigned to azathioprine plus prednisone and 15/44 (34%) participants assigned to prednisone. Nicotinamide plus tetracycline versus prednisone It is unclear whether nicotinamide plus tetracycline compared to prednisone affects skin healing or mortality because there was only very low-certainty evidence from one trial (18 participants). This study did not measure quality of life. Fewer adverse events were reported in the nicotinamide group. Methylprednisolone plus azathioprine versus methylprednisolone plus dapsone It is unclear whether azathioprine plus methylprednisolone compared to dapsone plus methylprednisolone affects skin healing or mortality because there was only very low-certainty evidence from one trial (54 participants). This study did not measure quality of life. A total of 18 adverse events were reported in the azathioprine group and 13 in the dapsone group.
AUTHORS' CONCLUSIONS
Clobetasol propionate cream applied over the whole body is probably similarly effective as, and may cause less mortality than, oral prednisone for treating bullous pemphigoid. Lower-dose clobetasol propionate cream applied over the whole body is probably similarly effective as standard-dose clobetasol propionate cream and has similar mortality. Doxycycline is less effective but causes less mortality than prednisolone for treating bullous pemphigoid. Other treatments need further investigation.
Topics: Humans; Azathioprine; Prednisone; Clobetasol; Pemphigoid, Bullous; Doxycycline; Methylprednisolone; Dapsone; Niacinamide
PubMed: 37572360
DOI: 10.1002/14651858.CD002292.pub4 -
Frontiers in Medicine 2023We assessed the efficacies of various corticosteroid treatments for preventing postexubation stridor and reintubation in mechanically ventilated adults with planned...
OBJECTIVES
We assessed the efficacies of various corticosteroid treatments for preventing postexubation stridor and reintubation in mechanically ventilated adults with planned extubation.
METHODS
We searched the Pubmed, Embase, the Cochrane databases and ClinicalTrial.gov registration for articles published through September 29, 2022. Only randomized controlled trials (RCTs) that compared the clinical efficacies of systemic corticosteroids and other therapeutics for preventing postextubation stridor and reintubation were included. The primary outcome was postextubation stridor and the secondary outcome was reintubation.
RESULTS
The 11 assessed RCTs reported 4 nodes: methylprednisolone, dexamethasone, hydrocortisone, and placebo, which yielded 3 possible pairs for comparing the risks of post extubation stridor and 3 possible pairs for comparing the risks of reintubation. The risk of postextubation stridor was significantly lower in dexamethasone- and methylprednisolone-treated patients than in placebo-treated patients (dexamethasone: OR = 0.39; 95% CI = 0.22-0.70; methylprednisolone: OR = 0.22; 95% CI = 0.11-0.41). The risk of postextubation stridor was significantly lower in methylprednisolone-treated patients than in hydrocortisone-treated: OR = 0.24; 95% CI = 0.08-0.67) and dexamethasone-treated patients: OR = 0.55; 95% CI = 0.24-1.26). The risk of reintubation was significantly lower in dexamethasone- and methylprednisolone-treated patients than in placebo-treated patients: (dexamethasone: OR = 0.34; 95% CI = 0.13-0.85; methylprednisolone: OR = 0.42; 95% CI = 0.25-0.70). Cluster analysis showed that dexamethasone- and methylprednisolone-treated patients had the lowest risks of stridor and reintubation. Subgroup analyses of patients with positive cuff-leak tests showed similar results.
CONCLUSIONS
Methylprednisolone and dexamethasone were the most effective agents against postextubation stridor and reintubation.
PubMed: 37554508
DOI: 10.3389/fmed.2023.1135570 -
Aesthetic Plastic Surgery Apr 2024Mycobacterium abscessus infection after liposuction/fat grafting is a rare complication that is hard to diagnose and treat. Misdiagnosis could result in treatment... (Review)
Review
Complicated Surgical Site Infection with Mycobacterium Abscessus After Liposuction and Affections of Corticosteroids in the Treatment Regimen: Three Cases Report and a Systematic Review.
INTRODUCTION
Mycobacterium abscessus infection after liposuction/fat grafting is a rare complication that is hard to diagnose and treat. Misdiagnosis could result in treatment failure and prolonged hospital stays. The paradoxical reaction is another complication that rarely occurs in non-HIV patients infected with nontuberculosis mycobacteria. This study reported 3 cases infected with M. abscessus complicated by the paradoxical reaction after liposuction and fat grafting. It highlighted characteristics giving clues of the paradoxical reaction and a successful strategy. Also, a systematic review was conducted to comprehensively provide varied aspects of M. abscessus infection after liposuction and/or fat grafting.
METHODS
Three cases were retrospectively included reporting data characteristics of patients, cosmetic procedures, and treatment strategy. PubMed, Scopus, Virtual Health Library (VHL), and Global Health Library (GHL) were searched to find and include cases with M. abscessus infection after liposuction and/or fat grafting based on defined selection criteria. Relevant data were extracted and summarized. The risk of bias in included studies was assessed using JBI critical appraisal checklists.
RESULTS
Twenty-four articles were included in the systematic review. Symptoms often developed approximately 1 month after the cosmetic surgery. Culture, AFB, and PCR were common methods of diagnosis of M. abscessus after liposuction and/or fat grafting. It took about 33 days on average from the presentation to isolate and detect the pathogens. Antibiotics based on susceptibility testing results along with surgical interventions were effective methods of treatment. Our three cases which were complicated by the paradox were addressed by adding methylprednisolone for 2 weeks to the macrolide-based therapy.
CONCLUSIONS
Awareness of this disease should be widely raised among physicians for early diagnosis and proper treatments. Cultures of specimens and AFB should be repeated many times before excluding the possibility of Mycobacterium spp. A paradoxical reaction should be suspected if the symptoms were worse after the antibiotic therapy based on susceptibility testing results and proper surgical interventions, especially if patients had taken corticosteroids before being admitted.
LEVEL OF EVIDENCE III
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
PubMed: 37530819
DOI: 10.1007/s00266-023-03512-x