-
International Orthopaedics Jan 2024Knowledge of Candida spondylodiscitis is limited to case reports and smaller case series. Controversy remains on the most effective diagnostical and therapeutical steps... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Knowledge of Candida spondylodiscitis is limited to case reports and smaller case series. Controversy remains on the most effective diagnostical and therapeutical steps once Candida is suspected. This systematic review summarized all cases of Candida spondylodiscitis reported to date concerning baseline demographics, symptoms, treatment, and prognostic factors.
METHODS
A PRISMA-based search of PubMed, Web of Science, Embase, Scopus, and OVID Medline was performed from database inception to November 30, 2022. Reported cases of Candida spondylodiscitis were included regardless of Candida strain or spinal levels involved. Based on these criteria, 656 studies were analyzed and 72 included for analysis. Kaplan-Meier curves, Fisher's exact, and Wilcoxon's rank sum tests were performed.
RESULTS
In total, 89 patients (67% males) treated for Candida spondylodiscitis were included. Median age was 61 years, 23% were immunocompromised, and 15% IV drug users. Median length of antifungal treatment was six months, and fluconazole (68%) most commonly used. Thirteen percent underwent debridement, 34% discectomy with and 21% without additional instrumentation. Median follow-up was 12 months. The two year survivorship free of death was 80%. The two year survivorship free of revision was 94%. Younger age (p = 0.042) and longer length of antifungal treatment (p = 0.061) were predictive of survival.
CONCLUSION
Most patients affected by Candida spondylodiscitis were males in their sixties, with one in four being immunocompromised. While one in five patients died within two years of diagnosis, younger age and prolonged antifungal treatment might play a protective role.
Topics: Male; Humans; Middle Aged; Female; Candida; Antifungal Agents; Discitis; Candidiasis; Immunocompromised Host
PubMed: 37792014
DOI: 10.1007/s00264-023-05989-2 -
The Journal of Laryngology and Otology Feb 2024Necrotising otitis externa is a serious infection with minimal evidence underpinning its management. This review aims to synthesise published evidence of antimicrobial... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Necrotising otitis externa is a serious infection with minimal evidence underpinning its management. This review aims to synthesise published evidence of antimicrobial therapies and their outcomes in necrotising otitis externa.
METHODS
The review was PROSPERO registered (CRD42022353244) and conducted according to Preferred Reporting Items for Systematic Review and Meta-Analyses ('PRISMA') guidelines. A robust search strategy filtered 28 manuscripts into the final review. Antimicrobial therapy and clinical outcome data were extracted and analysed.
RESULTS
Published studies are heterogeneous, with high risk of bias and low certainty. Reporting of outcomes is poor and extremely variable. First-line therapy is most commonly in-patient (95 per cent) empiric fluoroquinolone (68 per cent) delivered intravenously (82 per cent). The lack of granular data and poor outcome reporting mean it is impossible to correlate treatment strategies with clinical outcomes.
CONCLUSION
Robust, consistent outcome reporting with reference to treatments administered is mandatory, to inform clinical management and optimise future research. Optimal antimicrobial choices and treatment strategies require clarification through prospective clinical trials.
Topics: Humans; Otitis Externa; Anti-Bacterial Agents; Prospective Studies; Anti-Infective Agents
PubMed: 37767726
DOI: 10.1017/S0022215123001664 -
ASAIO Journal (American Society For... Dec 2023Extracorporeal membrane oxygenation (ECMO) may improve survival in patients with severe acute respiratory distress syndrome (ARDS). However, presence of...
Extracorporeal membrane oxygenation (ECMO) may improve survival in patients with severe acute respiratory distress syndrome (ARDS). However, presence of immunosuppression is a relative contraindication for ECMO, which is withheld in HIV patients. We performed a systematic review to investigate the outcome of newly diagnosed HIV patients with ARDS receiving ECMO support. Our search yielded 288 publications, with 22 studies finally included. Initial presentation included fever, respiratory distress, and cough. Severe immunodeficiency was confirmed in most patients. Deceased patients had a higher viral load, a lower Horovitz index, and antiretroviral therapy utilized before ECMO. Moreover, ECMO duration was longer ( p = 0.0134), and all deceased suffered from sepsis ( p = 0.0191). Finally, despite the development of therapeutic options for HIV patients, ECMO remains a relative contraindication. We found that ECMO may successfully bridge the time for pulmonary recovery in 93% of patients, with a very good outcome. Using ECMO, the time for antimicrobial therapy, lung-protective ventilation, and immune system restitution may be gained. Further studies clarifying the role of ECMO in HIV are crucial and until these data are available, ECMO might be appropriate in immunocompromised patients. This holds especially true in newly diagnosed HIV patients, who are usually young, without comorbidities, with a good rehabilitation potential.
Topics: Humans; Extracorporeal Membrane Oxygenation; HIV Infections; Respiratory Distress Syndrome; Lung; Respiration, Artificial
PubMed: 37738393
DOI: 10.1097/MAT.0000000000002047 -
Transplantation Reviews (Orlando, Fla.) Dec 2023Despite its use to prevent acute rejection, lifelong immunosuppression can adversely impact long-term patient and graft outcomes. In theory, immunosuppression withdrawal... (Review)
Review
INTRODUCTION
Despite its use to prevent acute rejection, lifelong immunosuppression can adversely impact long-term patient and graft outcomes. In theory, immunosuppression withdrawal is the ultimate goal of kidney transplantation, and is made possible by the induction of immunological tolerance. The purpose of this paper is to review the safety and efficacy of immune tolerance induction strategies in living-donor kidney transplantation, both chimerism-based and non-chimerism-based. The impact of these strategies on transplant outcomes, including acute rejection, allograft function and survival, cost, and immune monitoring, will also be discussed.
MATERIALS AND METHODS
Databases such as PubMed, Scopus, and Web of Science, as well as additional online resources such as EBSCO, were exhaustively searched. Adult living-donor kidney transplant recipients who developed chimerism-based tolerance after concurrent bone marrow or hematopoietic stem cell transplantation or those who received non-chimerism-based, non-hematopoietic cell therapy using mesenchymal stromal cells, dendritic cells, or regulatory T cells were studied between 2000 and 2021. Individual sources of evidence were evaluated critically, and the strength of evidence and risk of bias for each outcome of the transplant tolerance study were assessed.
RESULTS
From 28,173 citations, 245 studies were retrieved after suitable exclusion and duplicate removal. Of these, 22 studies (2 RCTs, 11 cohort studies, 6 case-control studies, and 3 case reports) explicitly related to both interventions (chimerism- and non-chimerism-based immune tolerance) were used in the final review process and were critically appraised. According to the findings, chimerism-based strategies fostered immunotolerance, allowing for the safe withdrawal of immunosuppressive medications. Cell-based therapy, on the other hand, frequently did not induce tolerance except for minimising immunosuppression. As a result, the rejection rates, renal allograft function, and survival rates could not be directly compared between these two groups. While chimerism-based tolerance protocols posed safety concerns due to myelosuppression, including infections and graft-versus-host disease, cell-based strategies lacked these adverse effects and were largely safe. There was a lack of direct comparisons between HLA-identical and HLA-disparate recipients, and the cost implications were not examined in several of the retrieved studies. Most studies reported successful immunosuppressive weaning lasting at least 3 years (ranging up to 11.4 years in some studies), particularly with chimerism-based therapy, while only a few investigators used immune surveillance techniques. The studies reviewed were often limited by selection, classification, ascertainment, performance, and attrition bias.
CONCLUSIONS
This review demonstrates that chimerism-based hematopoietic strategies induce immune tolerance, and a substantial number of patients are successfully weaned off immunosuppression. Despite the risk of complications associated with myelosuppression. Non-chimerism-based, non-hematopoietic cell protocols, on the other hand, have been proven to facilitate immunosuppression minimization but seldom elicit immunological tolerance. However, the results of this review must be interpreted with caution because of the non-randomised study design, potential confounding, and small sample size of the included studies. Further validation and refinement of tolerogenic protocols in accordance with local practice preferences is also warranted, with an emphasis on patient selection, cost ramifications, and immunological surveillance based on reliable tolerance assays.
Topics: Adult; Humans; Kidney Transplantation; Living Donors; Immune Tolerance; Hematopoietic Stem Cell Transplantation; Transplantation, Homologous; Transplantation Tolerance
PubMed: 37709652
DOI: 10.1016/j.trre.2023.100792 -
Frontiers in Immunology 2023Despite children and young people (CYP) having a low risk for severe coronavirus disease 2019 (COVID-19) outcomes, there is still a degree of uncertainty related to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite children and young people (CYP) having a low risk for severe coronavirus disease 2019 (COVID-19) outcomes, there is still a degree of uncertainty related to their risk in the context of immunodeficiency or immunosuppression, primarily due to significant reporting bias in most studies, as CYP characteristically experience milder or asymptomatic COVID-19 infection and the severe outcomes tend to be overestimated.
METHODS
A comprehensive systematic review to identify globally relevant studies in immunosuppressed CYP and CYP in general population (defined as younger than 25 years of age) up to 31 October 2021 (to exclude vaccinated populations) was performed. Studies were included if they reported the two primary outcomes of our study, admission to intensive therapy unit (ITU) and mortality, while data on other outcomes, such as hospitalization and need for mechanical ventilation were also collected. A meta-analysis estimated the pooled proportion for each severe COVID-19 outcome, using the inverse variance method. Random effects models were used to account for interstudy heterogeneity.
FINDINGS
The systematic review identified 30 eligible studies for each of the two populations investigated: immunosuppressed CYP ( = 793) and CYP in general population ( = 102,022). Our meta-analysis found higher estimated prevalence for hospitalization (46% vs. 16%), ITU admission (12% vs. 2%), mechanical ventilation (8% vs. 1%), and increased mortality due to severe COVID-19 infection (6.5% vs. 0.2%) in immunocompromised CYP compared with CYP in general population. This shows an overall trend for more severe outcomes of COVID-19 infection in immunocompromised CYP, similar to adult studies.
INTERPRETATION
This is the only up-to-date meta-analysis in immunocompromised CYP with high global relevance, which excluded reports from hospitalized cohorts alone and included 35% studies from low- and middle-income countries. Future research is required to characterize individual subgroups of immunocompromised patients, as well as impact of vaccination on severe COVID-19 outcomes.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO identifier, CRD42021278598.
Topics: Adolescent; Adult; Child; Humans; Asymptomatic Infections; COVID-19; Hospitalization; Immunocompromised Host; Immunosuppression Therapy
PubMed: 37691952
DOI: 10.3389/fimmu.2023.1159269 -
Transplantation Reviews (Orlando, Fla.) Dec 2023Kidney transplant (KT) recipients of HLA identical siblings (HLAid) have lower immunological risk, but there are no specific recommendations for immunosuppression. Our... (Review)
Review
BACKGROUND
Kidney transplant (KT) recipients of HLA identical siblings (HLAid) have lower immunological risk, but there are no specific recommendations for immunosuppression. Our aim was to analyze evidence about results from HLAid living-donor recipients under different immunosuppression in the current era of immunological risk assessment.
METHODS
Systematic review of studies describing associations between outcomes of HLAid living-donor KT recipients according to their immunological risk and applied immunosuppression.
RESULTS
From 1351 studies, 16 (5636 KT recipients) were included in the analysis. All studies were retrospective, ten comparing immunosuppression strategies, and six immunological risk strata. Of those ten, six studies were published in 1990 or earlier and only three included tacrolimus. The evidence is poor, and the inclusion of calcineurin inhibitors does not demonstrate better results. Furthermore, only few studies describe different immunosuppression regimens according to the patient immunological risk and, in general, they do not include the assessment with new solid phase assays.
CONCLUSIONS
There are no studies analyzing the association of outcomes of HLAid KT recipients with current immunological risk tools. In the absence of evidence, no decision or proposal of immunosuppression adapted to modern immunological risk assessment can be made currently by the Descartes Working Group.
Topics: Humans; Kidney Transplantation; Living Donors; Retrospective Studies; Graft Survival; Graft Rejection; Immunosuppression Therapy; Transplant Recipients; Immunosuppressive Agents; HLA Antigens
PubMed: 37657355
DOI: 10.1016/j.trre.2023.100787 -
Frontiers in Pharmacology 2023Currently, the optimal therapy plan for idiopathic membranous nephropathy (IMN) remains controversial as there has been no comprehensive and systematic comparison of...
Currently, the optimal therapy plan for idiopathic membranous nephropathy (IMN) remains controversial as there has been no comprehensive and systematic comparison of therapy plans for IMN. Therefore, in this study, a Bayesian meta-analysis was used to systematically evaluate the clinical efficacy and safety of various intervention plans involving traditional Chinese medicine TWM in the treatment of IMN. An electronic search in 7 databases was conducted from their inception to August 2022 for all published randomized controlled trials (RCTs) of various intervention plans for IMN. Network meta-analysis (NMA) was performed by using software R, and the surface under the cumulative ranking area (SUCRA) probability curve was plotted for each outcome indicator to rank the efficacy and safety of different intervention plans. A total of 30 RCTs were included, involving 13 interventions. The results showed that (1) in terms of total remission (TR), ① GC + CNI + TWM was the best effective among all plans, and the addition and subtraction plan of CNI + TWM was the best effective for IMN; ② All plans involving TWM were more effective than GG; ③ Among monotherapy plans for IMN, TWM was more effective distinctly than GC, while TWM and CNI were similarly effective; ④ Among multidrug therapy plans for IMN, the addition of TWM to previously established therapy plans made the original plans more effective; ⑤The efficacy of combining TWM with other plans was superior to that of TWM alone. (2) In terms of lowering 24 h-UTP, GC + TWM was the best effective and more effective than TWM. (3) In terms of safety, there was no statistically significant difference between all groups. However, CNI + TWM was the safest. No serious adverse events (AEs) occurred in all the included studies. The addition of TWM may be beneficial to patients with IMN. It may enhance the efficacy of previously established treatment protocols without leading to additional safety risks. In particular, GC + CNI + TWM, GC + TWM, and CNI + TWM with better efficacy and higher safety can be preferred in clinical decision-making as the therapy plans for IMN.
PubMed: 37608889
DOI: 10.3389/fphar.2023.1183499 -
Neurology(R) Neuroimmunology &... Sep 2023Glial fibrillary acidic protein (GFAP) antibodies can associate with an astrocytopathy often presenting as a meningoencephalitis. Visual involvement has been reported...
BACKGROUND AND OBJECTIVES
Glial fibrillary acidic protein (GFAP) antibodies can associate with an astrocytopathy often presenting as a meningoencephalitis. Visual involvement has been reported but scarcely defined. We describe 2 cases of GFAP astrocytopathy with predominant visual symptoms and present a systematic review of the literature.
METHODS
We describe 2 patients with GFAP astrocytopathy from our neurology department. We performed a systematic review of the literature according to PRISMA guidelines, including all patients with this disease and available clinical data, focusing on visual involvement.
RESULTS
Patient 1 presented with bilateral optic disc edema and severe sudden bilateral loss of vision poorly responsive to therapy. Patient 2 showed bilateral optic disc edema, headache, and mild visual loss with complete recovery after steroids. We screened 275 records and included 84 articles (62 case reports and 22 case series) for a total of 592 patients. Visual involvement was reported in 149/592 (25%), with either clinical symptoms or paraclinical test-restricted abnormalities. Bilateral optic disc edema was found in 80/159 (50%) of patients investigated with fundoscopy, among which 49/80 (61%) were asymptomatic. One hundred (100/592, 17%) reported visual symptoms, often described as blurred vision or transient visual obscurations. Optic neuritis was rare and diagnosed in only 6% of all patients with GFAP astrocytopathy, often without consistent clinical and paraclinical evidence to support the diagnosis. Four patients (including patient 1) manifested a severe, bilateral optic neuritis with poor treatment response. In patients with follow-up information, a relapsing disease course was more frequently observed in those with vs without visual involvement (35% vs 11%, = 0.0035, OR 3.6 [CI 1.44-8.88]).
DISCUSSION
Visual system involvement in GFAP astrocytopathy is common and heterogeneous, ranging from asymptomatic bilateral optic disc edema to severe bilateral loss of vision, but optic neuritis is rare. GFAP CSF antibody testing should be considered in patients with encephalitis/meningoencephalitis or myelitis and bilateral optic disc edema, even without visual symptoms, and in patients with severe bilateral optic neuritis, especially when AQP4 antibodies are negative. Visual symptoms might associate with a higher relapse risk and help to identify patients who may require chronic immunosuppression.
Topics: Humans; Papilledema; Glial Fibrillary Acidic Protein; Meningoencephalitis; Optic Neuritis; Antibodies
PubMed: 37582612
DOI: 10.1212/NXI.0000000000200146 -
Clinical Gastroenterology and... Mar 2024There are limited data on the safety of immunosuppressive therapy use in individuals with immune-mediated diseases with a history of malignancy, particularly with newer... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
There are limited data on the safety of immunosuppressive therapy use in individuals with immune-mediated diseases with a history of malignancy, particularly with newer biologic and small-molecule treatments.
METHODS
We performed a systematic search of PubMed and Embase databases to identify studies examining the impact of immunosuppressive therapies on cancer recurrence across several immune-mediated diseases. Studies were pooled together using random-effects meta-analysis and stratified by type of treatment. Primary outcome was occurrence of incident cancers, defined as new or recurrent.
RESULTS
Our meta-analysis included 31 studies (17 inflammatory bowel disease, 14 rheumatoid arthritis, 2 psoriasis, and 1 ankylosing spondylitis) contributing 24,328 persons and 85,784 person-years (p-y) of follow-up evaluation. Rates of cancer recurrence were similar among individuals not on immunosuppression (IS) (1627 incident cancers, 43,765 p-y; 35 per 1000 p-y; 95% CI, 27-43), receiving an anti-tumor necrosis factor (571 incident cancers, 17,772 p-y; 32 per 1000 p-y; 95% CI, 25-38), immunomodulators (1104 incident cancers, 17,018 p-y; 46 per 1000 p-y; 95% CI, 31-61), combination immunosuppression (179 incident cancers, 2659 p-y; 56 per 1000 p-y; 95% CI, 31-81). Patients receiving ustekinumab (5 incident cancers, 213 p-y; 21 per 1000 p-y; 95% CI, 0-44) and vedolizumab (37 incident cancers, 1951 p-y; 16 per 1000 p-y; 95% CI, 5-26) had numerically lower rates of cancer. There were no studies on Janus kinase inhibitors. Stratification of studies by timing of immunosuppression initiation did not reveal a medication effect based on early (<5 years) or delayed treatment initiation.
CONCLUSIONS
In patients with immune-mediated diseases and a history of malignancy, we observed similar rates of cancer recurrence in those on no immunosuppression compared with different immunosuppressive treatments.
Topics: Humans; Immunosuppressive Agents; Immunosuppression Therapy; Immunologic Factors; Ustekinumab; Recurrence; Neoplasms; Inflammatory Bowel Diseases
PubMed: 37579866
DOI: 10.1016/j.cgh.2023.07.027 -
American Journal of Rhinology & Allergy Nov 2023Sublingual immunotherapy (SLIT) has been widely applied to treat patients with allergic rhinitis (AR). However, meta-analyses on the efficacy of SLIT in AR patients with... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Sublingual immunotherapy (SLIT) has been widely applied to treat patients with allergic rhinitis (AR). However, meta-analyses on the efficacy of SLIT in AR patients with asthma are still limited.
METHODS
Literature without language limitation published before October 28, 2022, were retrieved from PubMed, EMBASE, and Cochrane Library. STATA 16.0 software was used for the meta-analysis of the extracted data. The results reported were symptom scores, drug scores, adverse effects rates, and cost of treatment.
RESULTS
Ten studies involving 1722 patients met the inclusion criteria. The total rhinitis score (TRSS) (weighted mean difference [WMD] = -1.23, 95% CI: -1.39--1.06, < .001) and total asthma symptom score (TASS) (WMD = -1.00, 95% CI: -1.12-0.89, < .001) were significantly lower in the SLIT group than the placebo group. The SLIT group had higher rates of treatment-related adverse events (relative risk [RR] = 2.82, 95% CI: 1.77-4.48, < .001) and total costs of treatment (standardized mean difference [SMD] = 0.71, 95% CI: 0.45-0.97, < .001). There was no significant difference in inhaled corticosteroids (ICS) dose ( = .195), fractional exhaled nitric oxide (FeNO) ( = .158), forced expiratory volume in 1 s (FEV1) ( = .237), and direct costs of treatment ( = .630) between the SLIT and placebo groups.
CONCLUSION
SLIT may be a therapeutic method for improving rhinitis symptoms and asthma symptoms in AR patients with asthma. However, as there was significant heterogeneity in results, more high-quality and well-designed studies are needed in the future to elucidate the efficacy of SLIT.
Topics: Humans; Allergens; Rhinitis; Sublingual Immunotherapy; Rhinitis, Allergic; Asthma; Treatment Outcome
PubMed: 37559376
DOI: 10.1177/19458924231193528