Advances in allogeneic hematopoietic stem cell transplantation (alloHSCT) and supportive care over the past decade have reduced transplant and relapse-related mortality, leading to a greater number of long-term survivors. However, transplant-related late effects, such as cardiovascular disease (CVD) and metabolic diseases, are becoming significant concerns for this group. This review aims to address several key questions regarding cardiovascular late effects in alloHSCT recipients, including the long-term incidence of CVD-related events, the prevalence of risk factors, screening and management recommendations, and evidence for screening and prevention strategies. A literature search was conducted in PubMed Central using the National Library of Medicine search engine, covering all relevant research from inception to 2023. The initial search identified 751 research records, of which 41 were shortlisted based on specific criteria (≥18 years of age at the time of transplant, allogeneic transplant, and inclusion of more than 30 patients). Our review highlights published evidence confirming the increased CVD risk among alloHSCT recipients. This risk is especially pronounced among individuals who have developed traditional and modifiable risk factors or have been exposed to transplant-specific risk factors. Evidence of the use of traditional cardiac risk factor calculators in the alloHSCT population is limited, in addition, there is emerging evidence that general population calculators potentially underestimate CVD risk given the increased risk of CVD in the allogeneic group as a whole. Studies that develop and validate transplant recipient-specific CVD risk stratification tools appear to be severely lacking and the field\'s focus needs to be shifted here in the coming years. To improve patient engagement and adherence to CVD risk factor measures, we recommend that a multidisciplinary model involving both specialists and primary care physicians is crucial in ensuring regular follow-up in the community and to potentially improve adherence.

Human Respiratory Syncytial Virus (RSV) is a common cause of respiratory tract infections. Usually associated with infants and children, an increasing amount of evidence suggests that RSV can cause substantial morbidity and mortality in immunocompromised individuals, including recipients of bone marrow transplantation (BMT). The present systematic review was therefore designed in accordance with the PRISMA guidelines to collect available evidence about RSV infections in BMT recipients. Three medical databases (PubMed, Embase, and MedRxiv) were therefore searched for eligible observational studies published up to 30 September 2023 and collected cases were pooled in a random-effects model. Heterogeneity was assessed using I2 statistics. Reporting bias was assessed by means of funnel plots and regression analysis. Overall, 30 studies were retrieved, including 20,067 BMT cases and 821 RSV infection episodes. Of them, 351 were lower respiratory tract infections, and a total of 78 RSV-related deaths were collected. A pooled attack rate of 5.40% (95% confidence interval [95%CI] 3.81 to 7.60) was identified, with a corresponding incidence rate of 14.77 cases per 1000 person-years (95%CI 9.43 to 20.11), and a case fatality ratio (CFR) of 7.28% (95%CI 4.94 to 10.60). Attack rates were higher in adults (8.49%, 95%CI 5.16 to 13.67) than in children (4.79%, 95%CI 3.05 to 7.45), with similar CFR (5.99%, 95%CI 2.31 to 14.63 vs. 5.85%, 95%CI 3.35 to 10.02). By assuming RSV attack rates as a reference group, influenza (RR 0.518; 95%CI 0.446 to 0.601), adenovirus (RR 0.679, 95%CI 0.553 to 0.830), and human metapneumovirus (RR 0.536, 95%CI 0.438 to 0.655) were associated with a substantially reduced risk for developing corresponding respiratory infection. Despite the heterogeneous settings and the uneven proportion of adult and pediatric cases, our study has identified high attack rates and a substantial CFR of RSV in recipients of BMT, stressing the importance of specifically tailored preventive strategies and the need for effective treatment options.

Preclinical and clinical studies on the administration of bone marrow-derived cells to restore perfusion show conflicting results. We conducted a systematic review and meta-analysis on preclinical studies to assess the efficacy of bone marrow-derived cells in the hind limb ischemia model and identify possible determinants of therapeutic efficacy. In vivo animal studies were identified using a systematic search in PubMed and EMBASE on 10 January 2022. 85 studies were included for systematic review and meta-analysis. Study characteristics and outcome data on relative perfusion were extracted. The pooled mean difference was estimated using a random effects model. Risk of bias was assessed for all included studies. We found a significant increase in perfusion in the affected limb after administration of bone marrow-derived cells compared to that in the control groups. However, there was a high heterogeneity between studies, which could not be explained. There was a high degree of incomplete reporting across studies. We therefore conclude that the current quality of preclinical research is insufficient (low certainty level as per GRADE assessment) to identify specific factors that might improve human clinical trials.

Epidermolysis bullosa (EB) is a genodermatosis that lacks effective treatments and requires supportive care for its severe, life-threatening manifestations. Bone marrow transplantation (BMT) and its derived cells have been suggested to improve clinical symptoms and quality of life. A comprehensive search was conducted for publications evaluating BMT and bone marrow-derived mesenchymal stem cell (BM-MSC) therapy for EB in PubMed/MEDLINE, Google Scholar, and Cochrane databases from inception until June 2023. A total of 55 participants with severe forms of EB had BMT and/or BM-MSCs, with recessive dystrophic EB as the most common EB type; 53 (96.4%) patients had better wound healing, and 3 (5.5%) patients died of sepsis. The most common adverse events reported were graft failure, sepsis, graft-versus-host disease, and renal insufficiency. Allogeneic BMT is a high-risk procedure with possible benefits and adverse events. BM-MSCs revealed favorable outcomes to improve the safety of EB cell-based therapy by minimizing the risk of serious adverse events, reducing blisters, and accelerating wound healing. Further studies are needed to assess the treatment\'s long-term effects and clarify the risk/benefit ratio of procedure versus conventional therapy.

Hematopoietic stem-cell transplantation (HSCT) has emerged as a groundbreaking therapeutic option for acute myeloid leukemia (AML) and specific subtypes of acute lymphoblastic leukemia (ALL). The prognostic significance of the NOD2/CARD15 gene has been explored alongside various factors, encompassing diverse patient cohorts and gene variants. Siblings and unrelated donors used for stem cell transplantation exhibit significant associations between their genetic variations and graft-versus-host disease incidence. The transplantation of stem cells for leukemia patients involves numerous considerations, including patient survival, relapse rates, disease stage, donor and recipient ages, and compatibility. This study delved into research on the NOD2/CARD15 gene and its mutations to assess its suitability as a screening tool. A comprehensive literature search encompassing PubMed, ScienceDirect, and Google Scholar articles yielded 4,840 articles. After removing duplicates and applying inclusion and exclusion criteria, we narrowed the search results to 876 articles. Subsequent screening of abstracts and titles resulted in the selection of 230 relevant articles. Further exclusion of 198 articles unrelated to the research question led to the scrutinizing of 32 full-text articles, which were assessed against inclusion and exclusion criteria. Emphasis was placed on articles that specifically investigated the role of NOD2/CARD15 as a predictive factor for HSCT outcomes, ultimately resulting in the inclusion of 19 articles in this study. Single nucleotide polymorphisms (SNPs) such as NOD2 and CARD15 have demonstrated their potential as reliable genetic markers for predicting post-transplantation relapse and disease outcomes. Patients positive for these genetic markers have exhibited reduced overall survival and event-free survival and increased transplant-related mortality. Interventions with interferon-gamma and muramyl tripeptide phosphatidylethanolamine have been considered to mitigate the inflammatory effects of these SNPs, thus enhancing the influence of natural killer cells on abnormal cells and potentially extending patient survival. NOD2/CARD15 typing may aid in identifying patients at higher risk for relapse and improving their clinical outcomes after allogeneic stem cell transplant, particularly in ALL patients. However, no remarkable change was observed in AML patients. Additionally, this study underscores the pivotal roles of adaptive and innate immune responses and their interplay in stem cell transplant immunology.

OBJECTIVE: To compare the efficacy of common intra-articular injections used in the treatment of knee osteoarthritis, including corticosteroid (CS), hyaluronic acid (HA), platelet-rich plasma (PRP), and bone marrow aspirate concentrate (BMAC), with a minimum follow-up of 6-months.
METHODS: A literature search was conducted using the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in August 2022 in the following databases: PubMed/MEDLINE, Scopus, Cochrane Database of Controlled Trials, and the Cochrane Database of Systematic Reviews. Level I to II randomized clinical trials with a minimum follow-up of 6 months that investigated the treatments of interest were included. Patient-reported outcome scores for pain and function at baseline and at latest follow-up were extracted, and the change in scores was converted to uniform 0 to 100 scales. Arm-based Bayesian network meta-analysis using a random-effects model was created to compare the treatment arms in pain and function.
RESULTS: Forty-eight studies comprising a total of 9,338 knees were included. The most studied intra-articular injection was HA (40.9%), followed by placebo (26.2%), PRP (21.5%), CS (8.8%), and then BMAC (2.5%). HA and PRP both led to a significant improvement in pain compared with placebo. HA, PRP, and BMAC all led to a significant improvement in function scores when compared with placebo. Surface under the cumulative ranking curves (SUCRAs) of the interventions revealed that PRP, BMAC, and HA were the treatments with the highest likelihood of improvement in both pain and function, with overall SUCRA scores of 91.54, 76.46, and 53.12, respectively. The overall SUCRA scores for CS and placebo were 15.18 and 13.70, respectively.
CONCLUSIONS: At a minimum 6-month follow-up, PRP demonstrated significantly improved pain and function for patients with knee osteoarthritis compared with placebo. Additionally, PRP exhibited the highest SUCRA values for these outcomes when compared with BMAC, HA, and CS.
METHODS: Level II, meta-analysis of Level I to II studies.

BACKGROUND: Osteochondral lesions of the talus are common in patients suffering even minor trauma; timely diagnosis and treatment can prevent the development of early osteoarthritis. The objectives of this systematic review and meta-analysis were to evaluate the effects of additional procedures on arthroscopic ankle microperforations for osteochondral lesions.
METHODS: A systematic literature search was conducted using PubMed-Medline, Cochrane Central, and Google Scholar to select clinical studies analyzing the efficacy of platelet-rich plasma (PRP), hyaluronic acid (HA), and bone marrow concentrate (BMC) procedures. Ten articles following PRISMA guidelines with a total of 464 patients were included in this review. Quality assessment using MINORS was performed, and all studies demonstrated high quality.
RESULTS: The results of the systematic review showed benefits in all patients undergoing infiltrative therapy with PRP, hyaluronic acid, and BMC. The best results in terms of AOFAS score and VAS scale were found in patients undergoing PRP injection. The meta-analysis showed improvements in pain relief and return to daily activities in patients undergoing arthroscopic microperforations and PRP, although not reporting statistically significant results (p = 0.42).
CONCLUSIONS: All treatment strategies reported better scores compared to the control groups. Among the various treatments analyzed, the addition of PRP appears to be the most valuable probably for the larger population receiving this treatment, showing excellent outcomes in pain reduction, clinical outcomes, and return to daily activities.
METHODS: II.

BACKGROUND: Cell-based therapy represents a potential treatment for ischemic stroke (IS). Here, we performed a systematic review and meta-analysis to summarize the evidence provided by randomized controlled trials (RCTs) for the transplantation of bone marrow mononuclear cells (BMMNCs) in patients with IS in any phase after stroke.
METHODS: We searched several databases for relevant articles up to the 10th of March 2023, including MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov. Subgroup analyses were implemented to evaluate the dose and route of BMMNC administration. Statistical data were analyzed by Review Manager version 5.3 software.
RESULTS: Six RCTs were included in this article, including 177 patients who were treated by the transplantation of BMMNCs and 166 patients who received medical treatment. The three-month National Institutes of Health Stroke Scale (NIHSS) score indicated a favorable outcome for the BMMNC transplantation group (standardized mean difference (SMD), - 0.34; 95% confidence interval (CI), - 0.57 to - 0.11; P = 0.004). There were no significant differences between the two groups at six months post-transplantation with regards to NIHSS score (SMD 0.00; 95% CI - 0.26 to 0.27; P = 0.97), modified Rankin Scale (risk ratio (RR) 1.10; 95% CI 0.75 to 1.63; P = 0.62), Barthel Index change (SMD 0.68; 95% CI - 0.59 to 1.95; P = 0.29), and infarct volume change (SMD - 0.08; 95% CI - 0.42 to 0.26; P = 0.64). In addition, there was no significant difference between the two groups in terms of safety outcome (RR 1.24; 95% CI 0.80 to 1.91; P = 0.33).
CONCLUSIONS: Our meta-analysis demonstrated that the transplantation of BMMNCs was safe; however, the efficacy of this procedure requires further validation in larger RTCs.

UNASSIGNED: Hematopoietic stem cell transplantation (HSCT) is an effective treatment for aplastic anemia. Recently, peripheral blood stem cell transplantation (PBSCT) has gradually replaced traditional bone marrow transplantation (BMT). However, which graft source has a better therapeutic effect and prognosis for aplastic anemia (AA) remains unclear. Therefore, we conducted this systematic review and meta-analysis.
UNASSIGNED: We systematically searched PubMed, EMBASE, and the Cochrane Library without language limitations for studies using PBSCT or BMT for AA. Data were analyzed using the Open Meta-Analyst.
UNASSIGNED: We identified 17 of 18,749 studies, including seven comparative reports and nine single-arm reports, with a total of 3,516 patients receiving HSCT (1,328 and 2,188 patients received PBSCT and BMT, respectively). The outcomes of the comparative studies showed similar 5-year overall survival [OS; relative risk (RR) = 0.867; 95% confidence interval (CI), 0.747-1.006], similar transplant-related mortality (RR = 1.300; 95%CI, 0.790-2.138), graft failure rate (RR = 0.972; 95%CI, 0.689-1.372) between the PBSCT group and the BMT group, while the PBSCT group had a significantly higher incidence of chronic graft-versus-host disease (GVHD; RR = 1.796; 95% CI, 1.571-2.053) and a higher incidence of grade IV acute GVHD (RR = 1.560; 95% CI, 1.341-1.816) compared to the BMT group. The outcomes of single-arm reports showed similar 3-year OS and incidences of chronic GVHD, acute II-IV GVHD, III-IV GVHD, transplant-related mortality and graft failure rate between PBSCT and BMT.
UNASSIGNED: Before 2010, PBSCT was not superior to BMT in terms of 5-year OS, transplant-related mortality and graft failure rate, but it exhibited a higher risk of both chronic and acute GVHD. After 2010, PBSCT and BMT showed similar 3-year OS, GVHD risks, transplant-related mortality and graft failure rate. PB grafts are more suitable for HSCT of the AA for convenience and pain relief.
UNASSIGNED: www.crd.york.ac.uk/PROSPERO/, CRD42023412467.

OBJECTIVE: Bone marrow aspirate concentrate can be used as an additive to surgical treatment of osteochondral lesions of the talus. This systematic literature review aims to study the effect of the additional use of bone marrow aspirate concentrate on top of a surgical treatment for osteochondral lesions of the talus on clinical outcomes compared to surgical treatment alone.
METHODS: An online literature search was conducted using PubMed (Medline), Embase (Ovid), and the Cochrane library for all studies comparing a surgical intervention with bone marrow aspirate concentrate, with a surgical intervention without bone marrow aspirate concentrate. The methodological quality was rated according to the methodological index for non-randomised studies checklist. The primary outcome measure were clinical outcomes. Secondary outcome measures consisted of revision rate, complication rate, radiographic outcome measures and histological analyses. Subgroups were created based on type of surgical intervention used in the studies. If multiple articles were included in a subgroup, a linear random-effects model was used to compare the bone marrow aspirate concentrate-augmented group with the control group.
RESULTS: Out of 1006 studies found, eight studies with a total of 718 patients were included. The methodological quality, assessed according to the methodological index for non-randomised studies checklist, was weak. A significantly better functional outcome measures (p < 0.05) was found in the subgroup treated with bone marrow stimulation + bone marrow aspirate concentrate compared to the group treated with bone marrow stimulation alone, based on three non-blinded studies. No significant differences regarding clinical outcomes were found in the subgroups comparing matrix-induced autologous chondrocyte implantation with matrix-induced bone marrow aspirate concentrate, osteochondral autologous transplantation alone with osteochondral autologous transplantation + bone marrow aspirate concentrate and autologous matrix-induced chondrogenesis plus peripheral blood concentrate vs. matrix-associated stem cell transplantation bone marrow aspirate concentrate.
CONCLUSIONS: There is insufficient evidence to support a positive effect on clinical outcomes of bone marrow aspirate concentrate as an additive to surgical treatment of osteochondral lesions of the talus. However, based on the safety reports and initial results, sufficiently powered, patient- and researcher-blinded, prospective randomised controlled trials are justified and recommended. Until then, we advise not to implement a therapy (addition of bone marrow aspirate concentrate) without clinical evidence that justifies the additional costs involved.
METHODS: Level III.