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The Journal of Surgical Research Jun 2024Vascularized Composite Allografts (VCA) are usually performed in a full major histocompatibility complex mismatch setting, with a risk of acute rejection depending on... (Review)
Review
INTRODUCTION
Vascularized Composite Allografts (VCA) are usually performed in a full major histocompatibility complex mismatch setting, with a risk of acute rejection depending on factors such as the type of immunosuppression therapy and the quality of graft preservation. In this systematic review, we present the different immunosuppression protocols used in VCA and point out relationships between acute rejection rates and possible factors that might influence it.
METHODS
This systematic review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We systematically searched Medline (PubMed), Embase, and The Cochrane Library between November 2022 and February 2023, using following Mesh Terms: Transplant, Transplantation, Hand, Face, Uterus, Penis, Abdominal Wall, Larynx, and Composite Tissue Allografts. All VCA case reports and reviews describing multiple case reports were included.
RESULTS
We discovered 211 VCA cases reported. The preferred treatment was a combination of antithymocyte globulins, mycophenolate mofetil (MMF), tacrolimus, and steroids; and a combination of MMF, tacrolimus, and steroids for induction and maintenance treatment, respectively. Burn patients showed a higher acute rejection rate (P = 0.073) and were administered higher MMF doses (P = 0.020).
CONCLUSIONS
In contrast to previous statements, the field of VCA is not rapidly evolving, as it has encountered challenges in addressing immune-related concerns. This is highlighted by the absence of a standardized immunosuppression regimen. Consequently, more substantial data are required to draw more conclusive results regarding the immunogenicity of VCAs and the potential superiority of one immunosuppressive treatment over another. Future efforts should be made to report the VCA surgeries comprehensively, and muti-institutional long-term prospective follow-up studies should be performed to compare the number of acute rejections with influencing factors.
Topics: Humans; Graft Rejection; Composite Tissue Allografts; Immunosuppressive Agents; Vascularized Composite Allotransplantation; Immunosuppression Therapy; Acute Disease
PubMed: 38603944
DOI: 10.1016/j.jss.2024.02.019 -
Systematic Reviews Apr 2024Immunosuppressive therapy (IST) is the first choice for severe aplastic anemia (SAA) patients with hematopoietic stem cell transplantation (HSCT) limitation, and the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Immunosuppressive therapy (IST) is the first choice for severe aplastic anemia (SAA) patients with hematopoietic stem cell transplantation (HSCT) limitation, and the main factor limiting its efficacy is too few residual hematopoietic stem/progenitor cells (HSPC). Eltrombopag (EPAG), as a small molecule thrombopoietin receptor agonist, can stimulate the proliferation of residual HSPC and restore the bone marrow hematopoietic function of patients. In recent years, many studies have observed the efficacy and safety of IST combined with EPAG in the treatment of SAA, but the results are still controversial. The aim of this study is to systematically evaluate the efficacy and safety of IST combined with or without EPGA in the treatment of SAA.
METHODS
We conducted a systematic review of all relevant literature published up to January 19, 2024. Pooled odds ratio (OR) was calculated to compare the rates, along with 95% confidence intervals (CI) and p value to assess whether the results were statistically significant by Review Manager 5.4.1. The p values for the interactions between each subgroup were calculated by Stata 15.1. The Newcastle-Ottawa Scale and the Cochrane bias risk assessment tools were respectively used to evaluate the quality of the literature with cohort studies and randomized controlled trials. The Review Manager 5.4.1 and Stata 15.1 were used to assess bias risk and perform the meta-analysis.
RESULTS
A total of 16 studies involving 2148 patients were included. The IST combined with the EPAG group had higher overall response rate (ORR) than the IST group at 3 months (pooled OR = 2.10, 95% CI 1.58-2.79, p < 0.00001) and 6 months (pooled OR = 2.13, 95% CI 1.60-2.83, p < 0.00001), but the difference between the two groups became statistically insignificant at 12 months (pooled OR = 1.13, 95% CI 0.75-1.72, p = 0.55). The results of complete response rate (CRR) (pooled OR at 3 months = 2.73, 95% CI 1.83-4.09, p < 0.00001, 6 months = 2.76, 95% CI 2.08-3.67, p < 0.00001 and 12 months = 1.38, 95% CI 0.85-2.23, p = 0.19) were similar to ORR. Compared with the IST group, the IST combined with the EPAG group had better overall survival rate (OSR) (pooled OR = 1.70, 95% CI 1.15-2.51, p = 0.008), but there were no statistically significant differences in event-free survival rate (EFSR) (pooled OR = 1.40, 95% CI 0.93-2.13, p = 0.11), clonal evolution rate (pooled OR = 0.68, 95% CI 0.46-1.00, p = 0.05) and other adverse events between the two groups. The results of subgroup analysis showed that different ages were a source of heterogeneity, but different study types and different follow-up times were not. Moreover, all p-values for the interactions were greater than 0.05, suggesting that the treatment effect was not influenced by subgroup characteristics.
CONCLUSION
EPAG added to IST enables patients to achieve earlier and faster hematologic responses with a higher rate of complete response. Although it had no effect on overall EFSR, it improved OSR and did not increase the incidence of clonal evolution and other adverse events.
Topics: Humans; Immunosuppressive Agents; Anemia, Aplastic; Immunosuppression Therapy; Benzoates; Pathologic Complete Response; Treatment Outcome; Hydrazines; Pyrazoles
PubMed: 38576005
DOI: 10.1186/s13643-024-02515-2 -
International Journal of Infectious... Jun 2024Crusted scabies (CS, Norwegian scabies) is a severe form of scabies, characterized by hyper-infestation of Sarcoptes scabiei mites. CS is commonly associated with... (Review)
Review
OBJECTIVES
Crusted scabies (CS, Norwegian scabies) is a severe form of scabies, characterized by hyper-infestation of Sarcoptes scabiei mites. CS is commonly associated with immunosuppression but is also reported in overtly immunocompetent individuals. We reviewed immunosuppressive risk factors and comorbidities associated with CS.
METHODS
The National Library of Medicine (PubMed) database was reviewed for patient case reports of CS from January 1998 to July 2023. Two authors screened records for eligibility, extracted data, and one critically appraised the quality of the studies.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42023466126.
RESULTS
A total of 436 records were identified, of which 204 were included for systematic review. From these, 683 CS patients were included. CS impacted both genders equally. Adults (21-59 years) were more commonly affected (45.5%) compared to children (0-20 years, 21%). Corticosteroid use was the most prevalent immunosuppressive risk factor identified (27.7% of all cases). About 10.2% of reports were associated with HIV/AIDS, and 8.5% with HTLV-1 infection. 10.5% of patients were overtly immunocompetent with no known risk factors. Overall, 41 (6.0%) died, many subsequent to secondary bacteremia.
CONCLUSION
This study represents the first systematic review undertaken on immunosuppressive risk factors associated with CS. This provides insights into trends of immunosuppression and mechanisms of CS development.
Topics: Scabies; Humans; Risk Factors; Comorbidity; Female; Male; Adult; Immunocompromised Host; Middle Aged; Young Adult; Adolescent; Child; Animals; Infant; Sarcoptes scabiei; HIV Infections; Child, Preschool; HTLV-I Infections; Immunosuppression Therapy; Infant, Newborn
PubMed: 38570134
DOI: 10.1016/j.ijid.2024.107036 -
Hematology (Amsterdam, Netherlands) Dec 2024This article conducts a systematic review of eltrombopag combined with immunosuppressive therapy for the treatment of aplastic anemia (AA), to demonstrate the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This article conducts a systematic review of eltrombopag combined with immunosuppressive therapy for the treatment of aplastic anemia (AA), to demonstrate the effectiveness and safety of eltrombopag.
METHODS
PubMed, Cochrane Library, Embase, OVID, Web of Science, China National Knowledge Infrastructure, and Wanfang databases were searched. Studies that met the inclusion criteria were collected, ranging from the establishment of the database to August 2023. Two reviewers performed meta-analyses using the Cochrane systematic review method and RevMan 5.3 software.
RESULTS
This meta-analysis enrolled 5 studies with a total of 542 AA patients, including 274 in the experimental group and 268 in the control group. Meta-analyses were performed for efficacy and adverse reactions. The endpoint of effects included 6-month complete response (CR), 6-month partial response (PR), and 6-month overall response (OR). Eltrombopag combined with immunotherapy showed significant improvements in 6-month CR (OR: 2.20; 95% CI;1.54-3.12; < 0.0001) and 6-month OR (OR = 3.66, 95% CI 2.39-5.61, < 0.001)compared to immunosuppressive therapy for AA patients. In terms of safety, eltrombopag combined with immunosuppressive therapy showed significantly increased pigment deposition and abnormal liver function compared to immunosuppressive therapy alone.
CONCLUSION
Compared to immunosuppressive therapy alone, eltrombopag combined with immunosuppressive therapy showed significant improvements in 6-month CR and 6-month OR. However, it also resulted in increased pigment deposition and abnormal liver function in terms of safety.
Topics: Humans; Immunosuppressive Agents; Anemia, Aplastic; Randomized Controlled Trials as Topic; Immunosuppression Therapy; Benzoates; Hydrazines; Pyrazoles
PubMed: 38553907
DOI: 10.1080/16078454.2024.2335419 -
Clinical Journal of the American... Jun 2024Nonlupus full house nephropathy is a rare, complex entity: confusion arises by the low-quality evidence and the lack of consensus on nomenclature. This systematic review...
KEY POINTS
Nonlupus full house nephropathy is a rare, complex entity: confusion arises by the low-quality evidence and the lack of consensus on nomenclature. This systematic review supports that systemic lupus erythematosus and nonlupus full house nephropathy are distinct clinical entities, with comparable outcomes. The identification of three pathogenetic categories provides further clues for a shared clinical and diagnostic approach to the disease.
BACKGROUND
The presence of a full house pattern at immunofluorescence on kidney biopsy in a patient without clinical and laboratory features of systemic lupus erythematosus (SLE) has led to the descriptive term nonlupus full house nephropathy. This systematic review and meta-analysis focus on nonlupus full house nephropathy nomenclature, clinical findings, and outcomes.
METHODS
In a reiterative process, all identified terms for nonlupus full house nephropathy and other medical subject headings terms were searched in PubMed. Out of 344 results, 57 records published between 1982 and 2022 were included in the analysis. Clinical data of single patients from different reports were collected. Patients were classified into three pathogenetic categories, which were compared according to baseline characteristics, treatments, and outcomes.
RESULTS
Out of the 57 records, 61% were case reports. Nonlupus full house nephropathy was addressed with 17 different names. We identified 148 patients: 75 (51%) were men; median age 35 (23–58) years. Serum creatinine and proteinuria at onset were 1.4 (0.8–2.5) mg/dl and 5.7 (2.7–8.8) g/d. About half of patients achieved complete response. A causative agent was identified in 51 patients (44%), mainly infectious (41%). Secondary nonlupus full house nephropathy was mostly nonrelapsing with worse kidney function at onset compared with idiopathic disease ( = 0.001). Among the 57 patients (50%) with idiopathic nonlupus full house nephropathy, complete response was comparable between patients treated with immunosuppression and supportive therapy; however, proteinuria and creatinine at onset were higher in patients treated with immunosuppression ( = 0.09 and = 0.07). The remaining 7 patients (6%) developed SLE after a median follow-up of 5.0 (1.9–9.0) years.
CONCLUSIONS
Our data support that SLE and nonlupus full house nephropathy are distinct clinical entities, with comparable outcomes. A small subset of patients develops SLE during follow-up. Nonlupus full house nephropathy is addressed by many different names in the literature. The identification of three pathogenetic categories provides further clues for the management of the disease.
Topics: Humans; Kidney Diseases
PubMed: 38527995
DOI: 10.2215/CJN.0000000000000438 -
Clinical Reviews in Allergy & Immunology Apr 2024Peanut allergy is a leading cause of severe food reactions. This meta-analysis evaluates the efficacy and safety of epicutaneous immunotherapy (EPIT) compared to placebo... (Meta-Analysis)
Meta-Analysis Review
Peanut allergy is a leading cause of severe food reactions. This meta-analysis evaluates the efficacy and safety of epicutaneous immunotherapy (EPIT) compared to placebo for peanut-allergic individuals. After prospectively registering on PROSPERO, we searched three databases (PubMed, Google Scholar, and Cochrane CENTRAL) and 2 trial registries till September 2023. Analysis was conducted via RevMan where data was computed using risk ratios (RR). The Cochrane Risk of Bias tool and GRADE criteria were used to appraise and evaluate the evidence. From 4927 records, six multicenter randomized placebo-controlled trials comprising 1453 participants were included. The 250 µg EPIT group had a significant increase in successful desensitization compared to placebo (RR: 2.13 (95% C.I: 1.72, 2.64), P < 0.01, I = 0%), while the 100 µg EPIT group did not (RR: 1.54 (95% C.I: 0.92, 2.58), P = 0.10, I = 0%) (moderate certainty evidence). Moreover, there was a significant increase in local (RR: 1.69 (95% C.I: 1.06, 2.68), P = 0.03, I = 89%) and systemic adverse events (RR: 1.75 (95% C.I: 1.14, 2.69), P = 0.01, I = 0%) with EPIT. Additionally, individuals administered EPIT have an increased probability of requiring rescue medications like epinephrine (RR: 1.91 (95% C.I: 1.12, 3.28), P = 0.02, I = 0%) and topical corticosteroids (RR: 1.49 (95% C.I: 1.29, 1.73), P < 0.01, I = 0%) to treat adverse events. The association of adverse events post-treatment including anaphylaxis (RR: 2.31 (95% C.I: 1.00, 5.33), P = 0.05, I = 36%), skin/subcutaneous disorders like erythema or vesicles (RR: 0.93 (95% C.I: 0.79, 1.08), P = 0.33, I = 0%), and respiratory disorders like dyspnea or wheezing (RR: 0.94 (95% C.I: 0.77, 1.15), P = 0.55, I = 0%) with EPIT is inconclusive. EPIT, although effective in desensitization, is linked to an increased risk of adverse events. PROSPERO registration: CRD42023466600.
Topics: Peanut Hypersensitivity; Humans; Desensitization, Immunologic; Administration, Cutaneous; Allergens; Randomized Controlled Trials as Topic; Treatment Outcome; Arachis
PubMed: 38526693
DOI: 10.1007/s12016-024-08990-8 -
American Journal of Hematology Jun 2024Sickle cell disease (SCD)-related organ complications are a major cause of morbidity and mortality in patients with SCD. We sought to assess whether hematopoietic stem... (Meta-Analysis)
Meta-Analysis Review
Sickle cell disease (SCD)-related organ complications are a major cause of morbidity and mortality in patients with SCD. We sought to assess whether hematopoietic stem cell transplantation (HSCT) stabilizes, attenuates, or exacerbates organ decline. We performed a systematic review and meta-analysis of trials investigating organ function before and after HSCT in patients with SCD. We searched MEDLINE/PubMed and EMBASE up to September 21, 2023. Continuous data were expressed as standardized mean difference (SMD) and pooled in a weighted inverse-variance random-effects model; binomial data were expressed as risk ratio (RR) using the Mantel-Haenszel random-effects meta-analyses. Of 823 screened studies, 34 were included in this review. Of these, 17 (774 patients, 23.6% adults, 86.3% HLA-identical sibling donor, 56.7% myeloablative conditioning regimen) were included in the meta-analyses. Pulmonary function remained stable. Mean tricuspid regurgitant jet velocity decreased but did not reach statistical significance. In children, estimated glomerular filtration rate decreased (SMD -0.80, p = .01), and the presence of proteinuria increased (RR 2.00, p = <.01), while splenic uptake and phagocytic function improved (RR 0.31, p = <.01; RR 0.23, p = <.01). Cerebral blood flow improved (SMD -1.39, p = <.01), and a low incidence of stroke after transplantation in high-risk patients was found. Retinopathy and avascular osteonecrosis were investigated in only one study, showing no significant changes. While HSCT can improve some SCD-related organ dysfunctions, transplantation-related toxicity may have an adverse effect on others. Future research should focus on identifying individuals with SCD who might benefit most from HSCT and which forms of organ damage are more likely to exacerbate post-transplantation.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Anemia, Sickle Cell; Transplantation, Homologous; Transplantation Conditioning; Adult; Child
PubMed: 38517255
DOI: 10.1002/ajh.27297 -
Nutrients Feb 2024: Seafood allergy is a significant global health concern that greatly impacts a patient's quality of life. The intervention efficacy of oral immunotherapy (OIT), an... (Meta-Analysis)
Meta-Analysis
Intervention Efficacy of Slightly Processed Allergen/Meat in Oral Immunotherapy for Seafood Allergy: A Systematic Review, Meta-Analysis, and Meta-Regression Analysis in Mouse Models and Clinical Patients.
: Seafood allergy is a significant global health concern that greatly impacts a patient's quality of life. The intervention efficacy of oral immunotherapy (OIT), an emerging intervention strategy, for seafood allergy remains controversial. This study aimed to perform a systematic review and meta-analysis to evaluate the efficacy of slightly processed allergen/meat from fish and crustacea in OIT, both in mouse models and clinical patients. : A comprehensive literature search was performed in four mainstream databases and the EBSCOhost database to identify all relevant case-control and cohort studies. The aim was to elucidate the intervention efficacy, encompassing various processing methods and assessing the efficacy of multiple major allergens in OIT. : The meta-analysis included five case-control studies on crustacean allergens in mouse models and 11 cohort studies on meat from fish and crustacea in clinical patients for final quantitative assessments. In mouse models, crustacean allergen substantially decreased the anaphylactic score after OIT treatment (mean difference (MD) = -1.30, < 0.01). Subgroup analyses with low-level heterogeneities provided more reliable results for crab species (MD = -0.63, < 0.01, I = 0), arginine kinase allergen (MD = -0.83, < 0.01, I = 0), and Maillard reaction processing method (MD = -0.65, < 0.01, I = 29%), respectively. In clinical patients, the main meta-analysis showed that the slightly processed meat significantly increased the incidence rate of oral tolerance (OT, incidence rate ratio (IRR) = 2.90, < 0.01). Subgroup analyses for fish meat (IRR = 2.79, < 0.01) and a simple cooking treatment (IRR = 2.36, = 0.01) also demonstrated a substantial increase in the incidence rate of OT. Sensitivity and meta-regression analyses successfully identified specific studies contributing to heterogeneity in mouse models and clinical patients, although these studies did not impact the overall significant pooled effects. : This meta-analysis provides preliminary evidence for the high intervention efficacy of slightly processed allergen/meat from fish and crustacea in OIT, both in mouse models and clinical patients. The Maillard reaction and cooking processing methods may emerge as potentially effective approaches to treating allergen/meat in OIT for clinical patients, offering a promising and specific treatment strategy for seafood allergy. However, these findings should be interpreted cautiously, and further supporting evidence is necessary.
Topics: Animals; Mice; Humans; Allergens; Desensitization, Immunologic; Quality of Life; Food Hypersensitivity; Seafood; Administration, Oral
PubMed: 38474795
DOI: 10.3390/nu16050667 -
Frontiers in Allergy 2024Insulin-induced type III hypersensitivity reactions (HSRs) are exceedingly rare and pose complex diagnostic and management challenges. We describe a case of a...
Insulin-induced type III hypersensitivity reactions (HSRs) are exceedingly rare and pose complex diagnostic and management challenges. We describe a case of a 43-year-old woman with type 1 diabetes mellitus (DM), severe insulin resistance, and subcutaneous nodules at injection sites, accompanied by elevated anti-insulin IgG autoantibodies. Treatment involved therapeutic plasma exchange (TPE) and intravenous immunoglobulin (IVIg) as bridge therapy, followed by long-term immunosuppression, which reduced autoantibody levels and improved insulin tolerance. Given the limited treatment guidelines, we conducted a comprehensive literature review, identifying 16 similar cases. Most patients were females with a median age of 36.5 years; 63% had type 1 DM, and 44% had concurrent insulin resistance (56% with elevated autoantibodies). Treatment approaches varied, with glucocorticoids used in 67% of cases. Patients with type 1 DM were less responsive to steroids than those with type 2 DM, and had a more severe course. Of those patients with severe disease necessitating immunosuppression, 66% had poor responses or experienced relapses. The underlying mechanism of insulin-induced type III HSRs remains poorly understood. Immunosuppressive therapy reduces anti-insulin IgG autoantibodies, leading to short-term clinical improvement and improved insulin resistance, emphasizing their crucial role in the condition. However, the long-term efficacy of immunosuppression remains uncertain and necessitates continuous evaluation and further research.
PubMed: 38469413
DOI: 10.3389/falgy.2024.1357901 -
Annals of Medicine and Surgery (2012) Mar 2024This study aimed to analyze the Vaccine Adverse Event Reporting System (VAERS) database and systematically review the literature to provide a comprehensive analysis of...
Reversible cerebral vasoconstriction syndrome and posterior reversible encephalopathy syndrome following vaccination: analysis of the VAERS database and systematic review.
OBJECTIVES
This study aimed to analyze the Vaccine Adverse Event Reporting System (VAERS) database and systematically review the literature to provide a comprehensive analysis of reversible cerebral vasoconstriction syndrome (RCVS) and posterior reversible encephalopathy syndrome (PRES) secondary to vaccination.
METHODS
The authors analyzed the VAERS database and conducted a systematic review following PRISMA guidelines. The inclusion criteria for VAERS data were a score of ≥3 on the RCVS score and/or radiographic findings consistent with the diagnosis of RCVS or PRES. The systematic review was registered with PROSPERO.
RESULTS
Our combined data set included 29 cases (9 RCVS and 20 PRES). Most cases were women (72.4%) with a mean age of 50.7 years (SD 19.4 years). Most cases were associated with COVID-19 mRNA vaccines (58.6% Moderna, 20.7% Pfizer). Hypertension (37.9%), hyperlipidemia (13.7%), chronic kidney disease (CKD) (10.3%), and end-stage renal disease (6.8%) were common comorbidities. Furthermore, 20.6% (6/29) of cases were on immunosuppression therapy for various reasons. The mean time to symptom onset was 10.49 days after vaccination (SD 18.60), and the mean duration of hospitalization was 7.42 days (SD 5.94). The symptoms reported the most frequently were headache (41.3%), elevated blood pressure (31.0%), and emesis (17.2%). Typical radiographic findings included T2/FLAIR hyperintensities affecting the parieto-occipital lobes, indicative of vasogenic and/or cytotoxic edema.
CONCLUSIONS
This study provides a comprehensive analysis of postvaccine RCVS and PRES. Both disease states were seen most often in those with pre-existing risk factors such as female sex, age over 50, hypertension, renal disease, and immunosuppression. Vaccines and their associated immune response may cause endothelial dysfunction leading to cerebral vasospasm and loss of cerebral autoregulation. However, further research is required to understand the underlying pathophysiological mechanisms. Despite the associations found, the absolute risk of these syndromes remains extremely low compared to the immense benefits of vaccination.
PubMed: 38463101
DOI: 10.1097/MS9.0000000000001407