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Annals of the Rheumatic Diseases Oct 2023Haemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening systemic hyperinflammatory syndromes that can develop in most...
The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).
OBJECTIVE
Haemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening systemic hyperinflammatory syndromes that can develop in most inflammatory contexts. They can progress rapidly, and early identification and management are critical for preventing organ failure and mortality. This effort aimed to develop evidence-based and consensus-based points to consider to assist clinicians in optimising decision-making in the of diagnosis, treatment and monitoring of HLH/MAS.
METHODS
A multinational, multidisciplinary task force of physician experts, including adult and paediatric rheumatologists, haematologist/oncologists, immunologists, infectious disease specialists, intensivists, allied healthcare professionals and patients/parents, formulated relevant research questions and conducted a systematic literature review (SLR). Delphi methodology, informed by SLR results and questionnaires of experts, was used to generate statements aimed at assisting early decision-making and optimising the initial care of patients with HLH/MAS.
RESULTS
The task force developed 6 overarching statements and 24 specific points to consider relevant to early recognition of HLH/MAS, diagnostic approaches, initial management and monitoring of HLH/MAS. Major themes included the simultaneous need for prompt syndrome recognition, systematic evaluation of underlying contributors, early intervention targeting both hyperinflammation and likely contributors, careful monitoring for progression/complications and expert multidisciplinary assistance.
CONCLUSION
These 2022 EULAR/American College of Rheumatology points to consider provide up-to-date guidance, based on the best available published data and expert opinion. They are meant to help guide the initial evaluation, management and monitoring of patients with HLH/MAS in order to halt disease progression and prevent life-threatening immunopathology.
Topics: Child; Adult; Humans; United States; Lymphohistiocytosis, Hemophagocytic; Macrophage Activation Syndrome; Rheumatology; Consensus
PubMed: 37487610
DOI: 10.1136/ard-2023-224123 -
Arthritis & Rheumatology (Hoboken, N.J.) Oct 2023Haemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening systemic hyperinflammatory syndromes that can develop in most...
The 2022 EULAR/ACR Points to Consider at the Early Stages of Diagnosis and Management of Suspected Haemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS).
OBJECTIVE
Haemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening systemic hyperinflammatory syndromes that can develop in most inflammatory contexts. They can progress rapidly, and early identification and management are critical for preventing organ failure and mortality. This effort aimed to develop evidence-based and consensus-based points to consider to assist clinicians in optimising decision-making in the early stages of diagnosis, treatment and monitoring of HLH/MAS.
METHODS
A multinational, multidisciplinary task force of physician experts, including adult and paediatric rheumatologists, haematologist/oncologists, immunologists, infectious disease specialists, intensivists, allied healthcare professionals and patients/parents, formulated relevant research questions and conducted a systematic literature review (SLR). Delphi methodology, informed by SLR results and questionnaires of experts, was used to generate statements aimed at assisting early decision-making and optimising the initial care of patients with HLH/MAS.
RESULTS
The task force developed 6 overarching statements and 24 specific points to consider relevant to early recognition of HLH/MAS, diagnostic approaches, initial management and monitoring of HLH/MAS. Major themes included the simultaneous need for prompt syndrome recognition, systematic evaluation of underlying contributors, early intervention targeting both hyperinflammation and likely contributors, careful monitoring for progression/complications and expert multidisciplinary assistance.
CONCLUSION
These 2022 EULAR/American College of Rheumatology points to consider provide up-to-date guidance, based on the best available published data and expert opinion. They are meant to help guide the initial evaluation, management and monitoring of patients with HLH/MAS in order to halt disease progression and prevent life-threatening immunopathology.
Topics: Adult; Child; Humans; Lymphohistiocytosis, Hemophagocytic; Macrophage Activation Syndrome; Consensus; Physicians; Advisory Committees
PubMed: 37486733
DOI: 10.1002/art.42636 -
International Journal of Medical... Aug 2023As diagnostic and prognostic models developed by traditional statistics perform poorly in real-world, artificial intelligence (AI) and Big Data (BD) may improve the... (Review)
Review
BACKGROUND
As diagnostic and prognostic models developed by traditional statistics perform poorly in real-world, artificial intelligence (AI) and Big Data (BD) may improve the supply chain of heart transplantation (HTx), allocation opportunities, correct treatments, and finally optimize HTx outcome. We explored available studies, and discussed opportunities and limits of medical application of AI to the field of HTx.
METHOD
A systematic overview of studies published up to December 31st, 2022, in English on peer-revied journals, have been identified through PUBMED-MEDLINE-WEB of Science, referring to HTx, AI, BD. Studies were grouped in 4 domains based on main studies' objectives and results: etiology, diagnosis, prognosis, treatment. A systematic attempt was made to evaluate studies by the Prediction model Risk Of Bias ASsessment Tool (PROBAST) and the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD).
RESULTS
Among the 27 publications selected, none used AI applied to BD. Of the selected studies, 4 fell in the domain of etiology, 6 in the domain of diagnosis, 3 in the domain of treatment, and 17 in that of prognosis, as AI was most frequently used for algorithmic prediction and discrimination of survival, but in retrospective cohorts and registries. AI-based algorithms appeared superior to probabilistic functions to predict patterns, but external validation was rarely employed. Indeed, based on PROBAST, selected studies showed, to some extent, significant risk of bias (especially in the domain of predictors and analysis). In addition, as example of applicability in the real-world, a free-use prediction algorithm developed through AI failed to predict 1-year mortality post-HTx in cases from our center.
CONCLUSIONS
While AI-based prognostic and diagnostic functions performed better than those developed by traditional statistics, risk of bias, lack of external validation, and relatively poor applicability, may affect AI-based tools. More unbiased research with high quality BD meant for AI, transparency and external validations, are needed to have medical AI as a systematic aid to clinical decision making in HTx.
Topics: Humans; Artificial Intelligence; Big Data; Heart Transplantation; Prognosis; Retrospective Studies
PubMed: 37285695
DOI: 10.1016/j.ijmedinf.2023.105110 -
World Journal of Gastroenterology Feb 2024Most patients with advanced pancreatic neuroendocrine tumors (pNETs) die due to tumor progression. Therefore, identifying new therapies with low toxicity and good... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Most patients with advanced pancreatic neuroendocrine tumors (pNETs) die due to tumor progression. Therefore, identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant. In this perspective, metformin is emerging as a molecule of interest. Retrospective studies have described metformin, a widely used agent for the treatment of patients with type 2 diabetes mellitus (T2DM), to be effective in modulating different tumor-related events, including cancer incidence, recurrence and survival by inhibiting mTOR phosphorylation. This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.
AIM
To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and post-treatment outcomes of pNET.
METHODS
A systematic review of the published literature was undertaken, focusing on the role of T2DM and metformin in insurgence and prognosis of pNET, measured through outcomes of tumor-free survival (TFS), overall survival and progression-free survival.
RESULTS
A total of 13 studies (5674 patients) were included in this review. Analysis of 809 pNET cases from five retrospective studies (low study heterogeneity with = 0%) confirms the correlation between T2DM and insurgence of pNET (OR = 2.13, 95%CI = 1.56-4.55; < 0.001). The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients (hazard ratio = 1.84, 95%CI = 0.78-2.90; < 0.001). The study heterogeneity was intermediate, with = 51%. A few studies limited the possibility of performing pooled analysis in the setting of metformin; therefore, results were heterogeneous, with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.
CONCLUSION
T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients. Unfortunately, a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.
Topics: Humans; Metformin; Diabetes Mellitus, Type 2; Neuroendocrine Tumors; Retrospective Studies; Pancreatic Neoplasms; Neuroectodermal Tumors, Primitive
PubMed: 38515954
DOI: 10.3748/wjg.v30.i7.759 -
Cancer Medicine Aug 2023Liver transplantation has made significant progress in recent decades. Lung cancer is one of the most frequently occurring cancers after liver transplantation. However,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Liver transplantation has made significant progress in recent decades. Lung cancer is one of the most frequently occurring cancers after liver transplantation. However, the risk of lung cancer among liver transplant patients compared with the general population is unclear. The aim of this meta-analysis was to assess the risk of developing lung cancer after liver transplantation.
METHODS
All eligible studies published in PubMed, Web of Science, and Embase from database inception to April 2022 were included. Standardized incidence ratio was used to describe the increased risk of lung cancer in liver transplant recipients as compared with the general population. The random-effects model was used for the calculations. A funnel plot and Egger test were performed to assess the potential publication bias.
RESULTS
Our meta-analysis included 15 studies, which involved 76,897 liver transplantation patients. Studies included in this review showed significant heterogeneity (I = 65.3%; p < 0.001), which required a random-effects model for effect pooling. The results indicated a significant higher risk of developing lung cancer in liver transplant patients than the general population with a pooled SIR of 2.06 (95% CI: 1.73, 2.46, p < 0.001). When stratified by region, no significant regional difference was observed. It showed a similarly doubled risk of lung cancer in Europe and North America, but an insignificantly increased risk in Asian populations. The sensitivity analysis by removal and substitution of each literature did not change the results.
CONCLUSION
Our meta-analysis suggests that liver transplant patients are twice as likely as the general population to develop lung cancer. Further research on risk factors for the development of lung cancer after liver transplantation should be conducted and appropriate surveillance protocols should be developed to reduce the risk of its occurrence.
Topics: Humans; Liver Transplantation; Incidence; Risk Factors; Lung Neoplasms; North America
PubMed: 37351559
DOI: 10.1002/cam4.6265 -
Transplantation Reviews (Orlando, Fla.) Apr 2024Frailty, malnutrition and sarcopenia lead to a significant increase in morbidity and mortality before and after liver transplantation (LT). Prehabilitation attempts to... (Review)
Review
BACKGROUND
Frailty, malnutrition and sarcopenia lead to a significant increase in morbidity and mortality before and after liver transplantation (LT). Prehabilitation attempts to optimize physical fitness of individuals before major surgeries. To date, little is known about its impact on patients awaiting LT.
AIMS
The aim of our scoping review was to describe whether prehabilitation in patients awaiting LT is feasible and safe, and whether it leads to a change in clinical parameters before or after transplantation.
METHODS
We performed a systematic review of the literature from 1946 to November 2023 to identify prospective studies and randomized controlled trials of adult LT candidates who participated in an exercise training program.
RESULTS
Out of 3262 citations initially identified, six studies were included. Studies were heterogeneous in design, patient selection, intervention, duration, and outcomes assessed. All studies were self-described as pilot or feasibility studies and had a sample size ranging from 13 to 33. Two studies were randomized controlled trials. Two study restricted to patients with cirrhosis who were eligible for liver transplantation or on the transplant list. Exercise programs lasted between 6 and 12 weeks. In terms of feasibility, proportion of eligible patients that were recruited was between 54 and 100%. Program completion ranged between 38 and 90%. Interventions appeared safe with 9 (9.2%) adverse events noted. In the intervention group, improvements were generally noted in peak oxygen consumption and workload, 6-min walking distance, and muscle strength. One study suggested a decrease in post-transplant hospital length of stay.
CONCLUSIONS
Overall, it appears that prehabilitation with exercise training is feasible, and safe in patients awaiting LT. Higher quality and larger studies are needed to confirm its impact on pre- and post-transplantation-related outcomes.
Topics: Adult; Humans; Liver Transplantation; Preoperative Exercise; Prospective Studies; Exercise; Exercise Therapy; Quality of Life; Preoperative Care; Postoperative Complications
PubMed: 38367398
DOI: 10.1016/j.trre.2024.100835 -
Human Vaccines & Immunotherapeutics Dec 2023Patients received kidney transplantation (KTR) have a low seroconversion rate after vaccination. Our objective was to compare the seroconversion rates and adverse... (Meta-Analysis)
Meta-Analysis
A systematic review and meta-analysis of the seroconversion rates and adverse effects of COVID-19 mRNA vaccine and COVID-19 viral vector vaccine in kidney transplant recipient patients.
Patients received kidney transplantation (KTR) have a low seroconversion rate after vaccination. Our objective was to compare the seroconversion rates and adverse effects of additional different vaccinations in KTR patients in existing studies. Databases such as PubMed, Cochrane Library, Web of Science, Embase, ClinicalTrials.gov and others. Three high-quality RCT were included and showed no statistical difference in seroconversion rates between the two vaccines (RR = 0.93[0.76,1.13]). There was no statistical difference in seroconversion rates between the sexes, for men (RR = 0.93[0.69,1.25]) and women (RR = 0.91[0.62,1.33]). Among the adverse effects there was no statistically significant difference in fever (RR = 1.06[0.44,2.57]), while for injection site pain there was a statistically significant difference (RR = 1.14[1.18,1.84]). There was no significant difference in seroconversion rates in patients with KTR who received the two additional vaccines. Patients injected with the viral vector vaccine were less painful than those injected with the mRNA vaccine.
Topics: Female; Humans; Male; Antibodies, Viral; COVID-19; COVID-19 Vaccines; Kidney Transplantation; Seroconversion; Vaccination
PubMed: 37057765
DOI: 10.1080/21645515.2023.2196893 -
Frontiers in Immunology 2023Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ transplant outcomes. However, a critical appraisal of these studies and a demonstration of the prognostic value of complement-activating status over anti-HLA DSA mean fluorescence intensity (MFI) level are lacking.
METHODS
We conducted a systematic review, meta-analysis and critical appraisal evaluating the role of complement-activating anti-HLA DSAs on allograft outcomes in different solid organ transplants. We included studies through Medline, Cochrane, Scopus, and Embase since inception of databases till May 05, 2023. We evaluated allograft loss as the primary outcome, and allograft rejection as the secondary outcome. We used the Newcastle-Ottawa Scale and funnel plots to assess risk of bias and used bias adjustment methods when appropriate. We performed multiple subgroup analyses to account for sources of heterogeneity and studied the added value of complement assays over anti-HLA DSA MFI level.
RESULTS
In total, 52 studies were included in the final meta-analysis (11,035 patients). Complement-activating anti-HLA DSAs were associated with an increased risk of allograft loss (HR 2.77; 95% CI 2.33-3.29, p<0.001; I²=46.2%), and allograft rejection (HR 4.98; 95% CI 2.96-8.36, p<0.01; I²=70.9%). These results remained significant after adjustment for potential sources of bias and across multiple subgroup analyses. After adjusting on pan-IgG anti-HLA DSA defined by the MFI levels, complement-activating anti-HLA DSAs were significantly and independently associated with an increased risk of allograft loss.
DISCUSSION
We demonstrated in this systematic review, meta-analysis and critical appraisal the significant deleterious impact and the independent prognostic value of circulating complement-activating anti-HLA DSAs on solid organ transplant risk of allograft loss and rejection.
Topics: Humans; Graft Rejection; Organ Transplantation; Complement System Proteins; Transplantation, Homologous; HLA Antigens
PubMed: 37849755
DOI: 10.3389/fimmu.2023.1265796 -
Experimental and Clinical... Aug 2023Although several studies have explored the connection between corticosteroids and renal transplant surgical complications, these studies have overlooked several factors.... (Review)
Review
OBJECTIVES
Although several studies have explored the connection between corticosteroids and renal transplant surgical complications, these studies have overlooked several factors. In addition, no review of the literature, to our knowledge, has been conducted to evaluate corticosteroid dose and incidence of posttransplant surgical complications in these patients. Thus, our objective was to carry out a systematic investigation ofthe correlationbetween corticosteroids and surgical complications in renaltransplant patients.
MATERIALS AND METHODS
A systematic search was conducted on the PubMed and Embase databases from their inception until April 2023. Retrospective and prospective cohort studies were included if they met the association between corticosteroids and surgical complications. The search strategy was performed using MeSH and non-MeSH key words. Terms used in the electronic search included kidney transplant* OR kidney transplant(mesh) AND steroid* OR steroids(mesh) AND complication* OR intraoperative complications(mesh).
RESULTS
From 3274 articles, 8 articles were included in the systematic review. Six studies were conducted as retrospective cohorts and 2 studies as prospective cohorts. The mean age of patients included in the studies was 42.1 years. The studies were conducted between 1981 and 2023. Findings suggested that decreasing the postoperative corticosteroid dosage was associated with a lower incidence of various postoperative surgical complications.
CONCLUSIONS
We investigated the potential benefits of reducing the dose of corticosteroids following kidney transplant. Findings suggested thatreducing the dose of corticosteroids following kidney transplant might be a viable strategy for minimizing the risk of surgical complications. However, it is essential to note that the optimal dosage and duration of corticosteroid therapy after kidney transplant may vary for each patient and should be carefully determined by the health care provider.
Topics: Humans; Adult; Kidney Transplantation; Prospective Studies; Retrospective Studies; Adrenal Cortex Hormones; Databases, Factual; Postoperative Complications
PubMed: 37698397
DOI: 10.6002/ect.2023.0198 -
Frontiers in Neurology 2023Fabry disease (FD) is an X-chromosome-linked disorder characterized by a reduced or complete absence of the enzyme α-galactosidase, resulting in the accumulation of...
BACKGROUND
Fabry disease (FD) is an X-chromosome-linked disorder characterized by a reduced or complete absence of the enzyme α-galactosidase, resulting in the accumulation of lysosomal globotriaosylceramide. Despite the presence of these deposits in multiple organs, the problem of sleep disorders within this population has very rarely been documented.
OBJECTIVE
This study aimed to investigate the types and prevalence of sleep disorders among patients with FD.
METHODS
Screening of the following medical databases using key terms was performed on 10 February 2023: PubMed, Scopus, and Embase. A total of 136 records were identified. The quality assessment of the studies was conducted by using tools from the National Institutes of Health (NIH) and critical appraisal tools from the Joanna Briggs Institute (JBI).
RESULTS
The study included nine studies on sleep disorders in patients with FD. The overall quality of the majority of these studies was assessed as either poor or fair. Among 330 patients, there was a slightly higher representation of female patients (56%). Sleep problems manifested 4-5 years after the onset of FD and sometimes even after 10-11 years. Genotypes of disease associated with sleep problems were rarely described. Within the FD population, the most commonly reported conditions were excessive daytime sleepiness (EDS) as well as obstructive and central sleep apnea (OSA, CSA). However, EDS occurred more frequently in FD patients, while the prevalence of OSA and CSA was within the ranges observed in the general population. The studies included indicated a lack of association between organ impairment by primary disease and EDS and OSA. The effectiveness of enzyme replacement therapy (ERT) in treating sleep disorders was not demonstrated.
CONCLUSION
The findings of this report revealed the presence of many sleep-related disorders within the FD population. However, very few studies on this subject are available, and their limited results make it difficult to truly assess the real extent of the prevalence of sleep disturbances among these individuals. There is a need to conduct further studies on this topic, involving a larger group of patients. It is important to note that there are no guidelines available for the treatment of sleep disorders in patients with FD.
PubMed: 37869133
DOI: 10.3389/fneur.2023.1217618