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Critical Reviews in Oncology/hematology Apr 2024We conducted a systematic review and meta-analysis to evaluate outcomes after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in TP53-mutated... (Meta-Analysis)
Meta-Analysis Review
We conducted a systematic review and meta-analysis to evaluate outcomes after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in TP53-mutated myelodysplastic syndromes (MDS). A literature search was performed on PubMed, Cochrane, Embase, and Clinicaltrials.gov. After screening 626 articles, eight studies were included. Data were extracted following the PRISMA guidelines and analyzed using the meta-package by Schwarzer et al. We analyzed 540 patients. The pooled median 3 (1-5) year overall survival was 21% (95% CI 0.08-0.37, I2=91%, n=540). The pooled relapse rate was 58.9% (95% CI 0.38-0.77, I2=93%, n=487) at a median of 1.75 (1-3) years. The pooled 4-year progression- free survival was 34.8% (95% CI 0.15-0.57, I2=72%, n=105). Outcomes of Allo-HSCT for TP53-mutated MDS patients remain poor, with 21% OS at three years; however, Allo-HSCT confers a survival advantage as compared to non-transplant palliative therapies. Our findings suggest the need to explore novel therapeutic agents in prospective clinical trials.
Topics: Humans; Prospective Studies; Myelodysplastic Syndromes; Hematopoietic Stem Cell Transplantation; Progression-Free Survival; Transplantation Conditioning; Tumor Suppressor Protein p53
PubMed: 38423375
DOI: 10.1016/j.critrevonc.2024.104310 -
Infection and Drug Resistance 2024With the advent of COVID-19, the number of patients diagnosed with mucormycosis has increased, especially in developing countries. The reason behind this increase is... (Review)
Review
With the advent of COVID-19, the number of patients diagnosed with mucormycosis has increased, especially in developing countries. The reason behind this increase is that COVID-19 causes hypoxia that promotes the growth of fungus. To identify the association between mucormycosis and COVID-19, in critically ill or immunocompromised COVID-19 patients. The literature included in the review was researched from October 1, 2021, to November 1, 2022, by using the Google Scholar database as the search engine. Of the 20 articles included, there were 4 case reports, 2 case series, 10 narrative reviews, and 4 quantitative studies. Mucormycetes growth is caused by several factors, including hyperglycemia owing to previously existing diabetes or excessive use of steroids, increased ferritin levels owing to the inflammatory cascade initiated by COVID-19, and immunosuppression caused by the use of steroids or other immunosuppressive therapy. Reduced white-cell count and activity in COVID-19 leads to increased germination of fungal spores hence developing a catastrophic picture of rhinocerebral mucormycosis. Considering that the hematological patient is frequently treated with cortisone, immunosuppressed due to the underlying condition, but also through the administered therapy, the association with a possible diabetes makes this patient susceptible to developing rhinocerebral mucormycosis during COVID-19 infection. Despite being severe, the association between mucormycosis and COVID-19 is specific and treatable. Development of mucormycosis in hematological patients suffering from severe COVID-19 disease is dangerous, yet not compulsory and can be prevented. Using a common steroid-dose protocol with hyperbaric oxygen and necessary preventive measure reveals the disease as a superadded infection. Hypoxia, poor glycemic control and overuse of steroids or immunosuppressive drugs cause it.
PubMed: 38312523
DOI: 10.2147/IDR.S445458 -
The Pediatric Infectious Disease Journal May 2024Acute lower respiratory infection (ALRI) caused by respiratory viruses is among the most common causes of hospitalization and mortality in children. We aimed to identify... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute lower respiratory infection (ALRI) caused by respiratory viruses is among the most common causes of hospitalization and mortality in children. We aimed to identify risk factors for poor outcomes in children <5 years old hospitalized with ALRI caused by respiratory syncytial virus (RSV), influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
METHODS
We searched Embase, Medline and Global Health databases and included observational studies reporting risk factors for poor outcomes (defined as use of supplemental oxygen, mechanical ventilation, intensive care unit admission, prolonged hospital stay and mortality) published between January 2011 and January 2023. Two authors independently extracted data on study characteristics, outcomes and risk factors. Due to limited data, meta-analyses were only conducted for RSV-ALRI poor outcome risk factors using random effects model when there were at least 3 studies.
RESULTS
We included 30 studies. For RSV-related ALRI, significant risk factors based on meta-analysis were: neurological disease [odds ratio (OR): 6.14; 95% confidence intervals (CIs): 2.39-15.77], Down's syndrome (5.43; 3.02-9.76), chronic lung disease (3.64; 1.31-10.09), immunocompromised status (3.41; 1.85-6.29), prematurity (2.98; 1.93-4.59), congenital heart disease (2.80; 1.84-4.24), underlying disease (2.45; 1.94-3.09), age <2 months (2.29; 1.78-2.94), age <6 months (2.08; 1.81-2.39), viral coinfection (2.01; 1.27-3.19), low birth weight (1.88; 1.19-2.95) and being underweight (1.80; 1.38-2.35). For influenza-related ALRI, chronic conditions and age 6-24 months were identified as risk factors for poor outcomes. Cardiovascular disease, immunosuppression, chronic kidney disease, diabetes and high blood pressure were reported as risk factors for mortality due to SARS-CoV-2 associated ALRI.
CONCLUSIONS
These findings might contribute to the development of guidelines for prophylaxis and management of ALRI caused by RSV, influenza and SARS-CoV-2.
Topics: Infant, Newborn; Child; Humans; Infant; Child, Preschool; Influenza, Human; Respiratory Tract Infections; Infant, Premature; Hospitalization; Risk Factors; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections
PubMed: 38285519
DOI: 10.1097/INF.0000000000004258 -
BMC Pulmonary Medicine Jan 2024Noninvasive ventilation (NIV) is commonly used in patients with acute respiratory distress syndrome (ARDS). However, the incidence and distribution of treatment failure... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Noninvasive ventilation (NIV) is commonly used in patients with acute respiratory distress syndrome (ARDS). However, the incidence and distribution of treatment failure are unclear.
METHODS
A comprehensive online search was conducted to select potentially eligible studies with reports of the rate of NIV failure in patients with ARDS. A manual search was also performed to identify additional studies. Data were extracted to calculate the pooled incidences of NIV failure and mortality. Based on oxygenation, the severity of the disease was classified as mild, moderate, or severe ARDS. Based on etiologies, ARDS was defined as being of pulmonary origin or extrapulmonary origin.
RESULTS
We enrolled 90 studies in this meta-analysis, involving 98 study arms. The pooled incidence of NIV failure was 48% (n = 5847, 95% confidence interval [CI]: 43-52%). The pooled incidence of ICU mortality was 29% (n = 2363, 95%CI: 22-36%), and that of hospital mortality was 33% (n = 2927, 95%CI: 27-40%). In patients with mild, moderate, and severe ARDS, the pooled incidence of NIV failure was 30% (n = 819, 95%CI: 21-39%), 51% (n = 1332, 95%CI: 43-60%), and 71% (n = 525, 95%CI: 62-79%), respectively. In patients with pulmonary ARDS, it was 45% (n = 2687, 95%CI: 39-51%). However, it was 30% (n = 802, 95%CI: 21-38%) in those with extrapulmonary ARDS. In patients with immunosuppression, the incidence of NIV failure was 62% (n = 806, 95%CI: 50-74%). However, it was 46% (n = 5041, 95%CI: 41-50%) in those without immunosuppression.
CONCLUSIONS
Nearly half of patients with ARDS experience NIV failure. The incidence of NIV failure increases with increasing ARDS severity. Pulmonary ARDS seems to have a higher rate of NIV failure than extrapulmonary ARDS. ARDS patients with immunosuppression have the highest rate of NIV failure.
Topics: Humans; Incidence; Noninvasive Ventilation; Respiratory Distress Syndrome; Hospital Mortality; Immunosuppression Therapy
PubMed: 38254064
DOI: 10.1186/s12890-024-02839-8 -
Frontiers in Immunology 2023To systematically compare the efficacy and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) in children with allergic rhinitis (AR). (Meta-Analysis)
Meta-Analysis
AIM
To systematically compare the efficacy and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) in children with allergic rhinitis (AR).
METHODS
PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to March 2, 2023. Outcomes included symptom scores (SSs), medication scores (MSs), symptom and medication scores (SMSs), new sensitizations, development of asthma, improvement, and treatment-related adverse events (TRAEs). The quality of the included studies was assessed by the modified Jadad scale and Newcastle-Ottawa scale (NOS). Meta-regression was carried out to explore the source of heterogeneity. Subgroup analysis was further conducted in terms of study design [randomized controlled trials (RCTs), cohort studies], allergen [house dust mites (HDMs), grass pollen], treatment duration (≥ 24, 12-23 or < 12 months), allergen immunotherapy (AIT) modality (drops or tablets), and AIT protocol [continuous, pre-seasonal, co-seasonal, or after the grass pollen season (GPS)]. Sensitivity analysis was conducted for all outcomes. A Bayesian framework and a Monte Carlo Markov Chain (MCMC) model were developed for indirect comparison.
RESULTS
Totally 50 studies with 10813 AR children were included, with 4122 treated with SLIT, 1852 treated with SCIT, and 4839 treated with non-SLIT or non-SCIT therapy. For direct comparison, the SLIT group had a similar SS to the SCIT group [pooled standardized mean difference (SMD): 0.41, 95% confidence interval (CI): -0.46, 1.28, = 0.353]. Comparable MSs were observed in the SLIT and SCIT groups (pooled SMD: 0.82, 95%CI: -0.88, 2.53, = 0.344). For indirect comparison, no significant differences were found in SSs (pooled SMD: 1.20, 95% credibility interval (CrI): -1.70, 4.10), MSs (pooled SMD: 0.57, 95%CrI: -1.20, 2.30), SMSs (pooled SMD: 1.80, 95%CrI: -0.005, 3.60), new sensitizations [pooled relative risk (RR): 0.34, 95%CrI: 0.03, 3.58], and development of asthma (pooled RR: 0.68, 95%CrI: 0.01, 26.33) between the SLIT and SCIT groups; the SLIT group illustrated a significantly lower incidence of TRAEs than the SCIT group (pooled RR: 0.17, 95%CrI: 0.11, 0.26).
CONCLUSION
Considering both efficacy and safety, SLIT might be a more favorable AIT than SCIT in the treatment of pediatric AR, which may serve as a decision-making reference for clinicians.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO (CRD42023460693).
Topics: Child; Humans; Allergens; Asthma; Desensitization, Immunologic; Pollen; Rhinitis, Allergic; Immunotherapy; Sublingual Immunotherapy
PubMed: 38162647
DOI: 10.3389/fimmu.2023.1274241 -
Clinical Transplantation Jan 2024Human-cytomegalovirus (hCMV) infection involving the gastrointestinal tract represents a leading cause of morbidity and mortality among kidney transplant (KT) recipients... (Review)
Review
BACKGROUND
Human-cytomegalovirus (hCMV) infection involving the gastrointestinal tract represents a leading cause of morbidity and mortality among kidney transplant (KT) recipients (KTRs). Signs and symptoms of the disease are extremely variable. Prompt anti-viral therapy administration and immunosuppression modification are key factors for optimizing management. However, complex work-up strategies are generally required to confirm the preliminary diagnosis. Unfortunately, solid evidence and guidelines on this specific topic are not available. We consequently aimed to summarize current knowledge on post-KT hCMV-related gastrointestinal disease (hCMV-GID).
METHODS
We conducted a systematic review (PROSPERO ID: CRD42023399363) about hCMV-GID in KTRs.
RESULTS
Our systematic review includes 52 case-reports and ten case-series, published between 1985 and 2022, collectively reporting 311 cases. The most frequently reported signs and symptoms of hCMV-GID were abdominal pain, diarrhea, epigastric pain, vomiting, fever, and GI bleeding. Esophagogastroduodenoscopy and colonoscopy were the primary diagnostic techniques. In most cases, the preliminary diagnosis was confirmed by histology. Information on anti-viral prophylaxis were extremely limited as much as data on induction or maintenance immunosuppression. Treatment included ganciclovir and/or valganciclovir administration. Immunosuppression modification mainly consisted of mycophenolate mofetil or calcineurin inhibitor minimization and withdrawal. In total, 21 deaths were recorded. Renal allograft-related outcomes were described for 26 patients only. Specifically, reported events were acute kidney injury (n = 17), transplant failure (n = 5), allograft rejection (n = 4), and irreversible allograft dysfunction (n = 3).
CONCLUSIONS
The development of local and national registries is strongly recommended to improve our understanding of hCMV-GID. Future clinical guidelines should consider the implementation of dedicated diagnostic and treatment strategies.
Topics: Humans; Kidney Transplantation; Cytomegalovirus; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Gastrointestinal Diseases
PubMed: 38063324
DOI: 10.1111/ctr.15218 -
Journal of Clinical Medicine Nov 2023With new variants challenging the effectiveness of preventive measures, we are beginning to recognize the reality that COVID-19 will continue to pose an endemic threat.... (Review)
Review
BACKGROUND
With new variants challenging the effectiveness of preventive measures, we are beginning to recognize the reality that COVID-19 will continue to pose an endemic threat. The manifestations of COVID-19 in lung transplant recipients during index admission are poorly understood with very few cases reported in recent lung transplant recipients. Optimal management of immunosuppression and antiviral therapy in recent transplant recipients is challenging.
METHODS
We performed a retrospective analysis identifying lung transplant recipients at our institution who contracted COVID-19 in the immediate postoperative period (within index admission). In addition, we performed a systematic review from January 2020 to August 2023 identifying all publications on the PUBMED database regarding COVID-19 infection in lung transplant recipients during index admission.
RESULTS
We report four cases of COVID-19 pneumonia in lung transplant recipients in the immediate postoperative period and we describe the clinical course, treatment options, and immunosuppression changes to manage this unique clinical problem. All patients made a full recovery and were eventually discharged home. Within our review of the literature, the most prevalent presenting symptoms were cough, dyspnea, and fatigue. Six (75%) patients decreased or held their antimetabolite. The two most common treatments were monoclonal antibodies (38%) and remdesivir (63%).
CONCLUSION
Although previous literature demonstrates that COVID-19 can be deadly in recent lung transplant recipients, rapid treatment with anti-viral therapy/immunotherapy, deescalating immunosuppression, and treatment of respiratory decompensation with Decadron was effective in our patients.
PubMed: 38002643
DOI: 10.3390/jcm12227028 -
Journal of Plastic, Reconstructive &... Dec 2023Since the first procedure performed in 2005, face transplantation has been debated as viable approach for the treatment of severe craniofacial defects. Despite the... (Review)
Review
BACKGROUND
Since the first procedure performed in 2005, face transplantation has been debated as viable approach for the treatment of severe craniofacial defects. Despite the benefits provided, the experience in face allotransplantation has brought to light a significant risk of complications, including allograft removal or loss, and mortality. The present study is intended to provide an updated review on complications and major challenges witnessed over 18 years of experience in the field.
METHODS
A systematic review of PubMed, MEDLINE, Cochrane, Google, and Google Scholar databases on face transplantation was conducted according to PRISMA guidelines up to April 2023. Articles providing details on cases of face allograft loss, removal, and patient death were included. Online articles and media reports were assessed to include information not disclosed in peer-reviewed literature. Face transplant centers were contacted to have updated follow-up information on single-face transplant cases.
RESULTS
The search yielded 1006 reports, of which 28 were included. On a total of 48 procedures performed in 46 patients, adverse outcomes were gleaned in 14 cases (29%), including seven allograft losses (14.6%), and the death of ten patients (21.7%). Chronic rejection was the leading cause of allograft loss, with a median time from transplant to irreversible rejection of 90 months (IQR 88.5-102). The main causes of death were infectious complications, followed by malignancies, non-compliance to immunosuppression, and suicide. The median time to death was 48.5 months (IQR 19-122).
CONCLUSIONS
To the best of our knowledge, this is the first study providing a comprehensive review of adverse outcomes in face transplantation. Considering the high rate of major complications, the heterogeneity of cases and single-center approaches, and the absence of published standards of care, the development of a consensus by face transplant teams holds the key to the field's advancement.
Topics: Humans; Facial Transplantation; Immunosuppression Therapy; Immune Tolerance; Graft Rejection
PubMed: 37879143
DOI: 10.1016/j.bjps.2023.09.043 -
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 -
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