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Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a type I transmembrane protein initially identified in nonmetastatic melanomas and has been associated with human heart failure; however, its role in cardiac injury and function remains unclear. Here we show that GPNMB expression is elevated in failing human and mouse hearts after myocardial infarction (MI). Lineage tracing and bone-marrow transplantation reveal that bone-marrow-derived macrophages are the main source of GPNMB in injured hearts. Using genetic loss-of-function models, we demonstrate that GPNMB deficiency leads to increased mortality, cardiac rupture and rapid post-MI left ventricular dysfunction. Conversely, increasing circulating GPNMB levels through viral delivery improves heart function after MI. Single-cell transcriptomics show that GPNMB enhances myocyte contraction and reduces fibroblast activation. Additionally, we identified GPR39 as a receptor for circulating GPNMB, with its absence negating the beneficial effects. These findings highlight a pivotal role of macrophage-derived GPNMBs in post-MI cardiac repair through GPR39 signaling.

Objective: Ideal implant placement in atrophied posterior mandibular regions is challenging due to surgical difficulties and anatomical limitations. This study aimed to evaluate the use of allogeneic bone rings for vertical augmentation of atrophied posterior mandibular regions with simultaneous implants compared to autogenous bone rings, while avoiding donor site morbidity. Method and materials: A total of 24 vertically atrophied posterior mandibular segments (in 14 patients) were equally randomized into a study group in which mineralized freeze-dried allogeneic bone rings were used, and a control group in which autogenous bone rings with prepared implant osteotomies were harvested from the chin and used. All augmentation sites were prepared before inserting the bone rings. Implants were simultaneously inserted, fixing the bone rings into the native bone. All patients were clinically assessed after 1 week, 2 weeks, and 1 month. Crestal bone level was radiographically assessed after lweek, 6 months, and 3 months of prosthetic loading. Results: None of the 24 bone rings showed signs of implant or graft failure. There was no significant difference in the crestal bone level between the groups. Conclusion: Allogeneic bone rings can be a viable alternative to autogenous bone rings in augmenting the posterior aspect of the mandible, mitigating the concerns associated with donor site complications. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cell transplantation can cure various disorders but poses cardiovascular risks, especially for elderly patients and those with cardiovascular diseases. Cardiovascular evaluations are crucial in pretransplantation assessments, but guidelines are lacking. This American Heart Association scientific statement summarizes the data on transplantation-related complications and provides guidance for the cardiovascular management throughout transplantation. Hematopoietic stem cell transplantation consists of 4 phases: pretransplantation workup, conditioning therapy and infusion, immediate posttransplantation period, and long-term survivorship. Complications can occur during each phase, with long-term survivors facing increased risks for late effects such as cardiovascular disease, secondary malignancies, and endocrinopathies. In adults, arrhythmias such as atrial fibrillation and flutter are the most frequent acute cardiovascular complication. Acute heart failure has an incidence ranging from 0.4% to 2.2%. In pediatric patients, left ventricular systolic dysfunction and pericardial effusion are the most common cardiovascular complications. Factors influencing the incidence and risk of complications include pretransplantation therapies, transplantation type (autologous versus allogeneic), conditioning regimen, comorbid conditions, and patient age. The pretransplantation cardiovascular evaluation consists of 4 steps: (1) initial risk stratification, (2) exclusion of high-risk cardiovascular disease, (3) assessment of cardiac reserve, and (4) optimization of cardiovascular reserve. Clinical risk scores could be useful tools for the risk stratification of adult patients. Long-term cardiovascular management of hematopoietic stem cell transplantation survivors includes optimizing risk factors, monitoring, and maintaining a low threshold for evaluating cardiovascular causes of symptoms. Future research should prioritize refining risk stratification and creating evidence-based guidelines and strategies to optimize outcomes in this growing patient population.

Background Objectives Materials and methods Results Discussion Conclusion It is not known whether bone marrow stem cells when injected intravenously for a bone marrow transplant colonize the human testicular epithelium. No previous studies of sperm genotype after bone marrow transplantation are reported.To differentiate host from donor genotype in spermatozoa of men who have undergone successful bone marrow transplants.Triplet DNA samples (spermatozoa, blood, and hair) obtained from men who had recovered sperm production after bone marrow transplant were genotyped using 44 autosomal and three sex‐related single nucleotide polymorphisms to determine the tissue genotype in pairwise comparisons of DNA profiles.Participants were 14 men at a median of 5.5 years after allogeneic bone marrow transplant who had a median sperm output of 77 million spermatozoa/ejaculate. In 14/14 the donor (leukocyte) DNA genotype differed significantly from the spermatozoa and hair genotypes whereas hair and sperm genotypes showed no variations.These data suggest that paternity after a successful bone marrow transplant is likely to be of the host and not the donor's genetic origins. The study's small sample size reflects the paucity of eligible man with recovered spermatogenesis after bone marrow transplant and represents preliminary evidence. A large‐scale epidemiological analysis to estimate the frequency of bone marrow donor stem cell colonization of the testicular germinal epithelium based on progeny sex ratio and frequency of female donors is proposed.Successful colonization of the testicular germinal and hair follicle epithelia by allogeneic bone marrow transplant donor stem cells is rare or does not occur. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs) are widely dispersed in vivo and are isolated from several tissues, including bone marrow, heart, body fluids, skin, and perinatal tissues. Bone marrow MSCs have a multidirectional differentiation potential, which can be induced to differentiate the medium in a specific direction or by adding specific regulatory factors. MSCs repair damaged tissues through lineage differentiation, and the ex vivo transplantation of bone marrow MSCs can heal injured sites. MSCs have different propensities for lineage differentiation and pathological evolution for different diseases, which are crucial in disease progression. In this study, we describe various lineage analysis methods to explore lineage ontology in vitro and in vivo, elucidate the impact of MSC lineage differentiation on diseases, advance our understanding of the role of MSC differentiation in physiological and pathological states, and explore new targets and ideas associated with disease diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Nijmegen breakage syndrome (NBS) is an autosomal recessive DNA repair disorder that manifests through increased genomic instability, malignancy, and cellular and humoral immunodeficiencies. The prognosis for NBS patients is poor due to their increased susceptibility to fatal infections and lymphoproliferative malignancies. Currently, there is no specific treatment for NBS, though allogeneic hematopoietic stem cell transplantation (HSCT) has been performed and documented as case series to demonstrate the utility of transplantation. Methods: A 14‐year‐old girl with NBS and haploidentical HSCT from her older brother due to recurrent lung infection was referred for liver transplantation (LT) due to liver cirrhosis, hepatopulmonary syndrome (HPS), and suspicion of liver malignancy. It was decided to perform LT using the living donor who had previously donated for HSCT. Results: Living donor left lobe LT was successfully performed from her brother. The patient experienced no complications in the early postoperative period and was discharged on the seventh postoperative day. Pathological examination of extracted liver has shown "intermediate cell carcinoma" in two foci. After 1 year LT, the patient has had an uneventful course in terms of LT complications and infection, with minimal immunosuppression. Conclusions: NBS patients have an increased prevalence of malignancies, including primary hepatic malignancy, but most are managed medically or with limited resections. Transplantation in these patients can be curative for hepatic malignancy with a favorable safety profile. [ABSTRACT FROM AUTHOR]

Pre-transplant lung dysfunction is known to be a risk factor for non-relapse mortality (NRM) after allogeneic hematopoietic cell transplantation (allo-HCT). It is unclear which cell source gives better outcomes for patients with pulmonary dysfunction. We analyzed 3289 adult patients with standard-risk disease who had received HLA-matched allo-HCT, and compared outcomes between those who received peripheral blood stem cell (PBSC) vs. bone marrow (BM) in two cohorts based on the presence of a lung score by the Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI): the Lung-scored (LS) and non-LS cohorts. In the LS cohort, the 2-year overall survival (OS) in the BM group tended to be higher than that in the PBSC group (72.4% vs. 61.4%; P = 0.044). In the non-LS cohort, there was no significant difference between the two groups (71.7% vs. 73.2%; P = 0.13). Multivariate analyses confirmed that PBSC was significantly associated with inferior OS in the LS cohort (hazard ratio [HR], 1.66; 95% CI, 1.09-2.54; P = 0.019). On the other hand, the cell source did not affect OS in the non-LS cohort (HR, 0.92; 95% CI, 0.76-1.12; P = 0.41). We found that PBSC was associated with an increased risk of NRM in the LS cohort (HR, 2.17; 95% CI, 1.16-4.05; P = 0.016), while the cell source did not significantly affect NRM in the non-LS cohort. PBSC was not identified as a risk factor for relapse in either cohort. Our results suggest that BM might be beneficial for recipients with lung dysfunction in HLA-matched allo-HCT. [Display omitted] • The use of PBSC was significantly associated with inferior OS and NRM in HCT-CI Lung-scored patients. • Patients in the HCT-CI Lung-scored cohort who received PBSC experienced a higher incidence of non-pulmonary infection-related deaths than those who received BM. [ABSTRACT FROM AUTHOR]

BK virus (BKV) encephalitis is a rare complication after hematopoietic stem cell transplantation (HSCT). A 43-year-old woman with recurrent follicular lymphoma after autologous HSCT received allogeneic bone marrow transplantation from a human leukocyte antigen-matched related donor. Neutrophil engraftment was achieved on post-transplant day 13. Memory loss and noncooperative attitude toward the medical staff were observed on day 16, and her mental status worsened progressively. Magnetic resonance imaging (MRI) showed nonspecific findings on day 19; however, cerebrospinal fluid (CSF) analysis including real-time polymerase chain reaction on day 20 revealed elevated levels of BKV 4.67 × 104 copy/mL. BKV encephalitis was diagnosed based on CSF findings, intravenous administration of immunoglobulin and cidofovir was started, and the immunosuppressive agent dose was reduced. Diffusion-weighted MRI on day 28 showed signal abnormalities in the bilateral periventricular white matter. Although the follow-up CSF analysis on day 35 was negative for BKV, her mental status and MRI findings did not improve, and she died on day 55 because of respiratory failure. This case emphasizes the importance of considering BKV encephalitis as a differential diagnosis of post-transplant encephalitis, considering the central nervous system-associated immune reconstitution inflammatory syndrome in patients with worsening central nervous system findings after eradication of BKV in the CSF. [ABSTRACT FROM AUTHOR]

Purpose: Total body irradiation before bone marrow transplantation for hematological malignancies using Radixact, a high‐precision radiotherapy machine, can potentially reduce side effects and the risk of secondary malignancies. However, stable control of couch speed is critical, and direct assessment methods outlined in quality assurance guidelines are lacking. This study aims to develop a real‐time couch speed verification system for the Radixact. Methods: The developed system used a linear encoder to measure couch speed directly. Accuracy was verified via a linear stage, comparing measurements with a laser distance sensor. After placing a phantom simulating the human body on the Radixact couch, the couch speed was verified using predefined speed plans. Results: Operating the linear stage at 0.1, 0.5, and 1.0 mm/s revealed that the maximum position error of the developed verification system compared to the laser distance sensor was nearly equivalent to the distance resolution of the system (0.05 mm/pulse), with negligible average speed error. When the Radixact couch operated at 0.1, 0.5, and 1.0 mm/s, the values obtained by the verification system agreed with the theoretical values within the sampling period (0.01 s) and distance resolution (0.05 mm). Conclusion: The verification system developed provides real‐time monitoring of the speed of the Radixact table, ensuring treatment effectiveness and patient safety. It would guarantee the couch speed's soundness and contribute to the "visualization" of safety. [ABSTRACT FROM AUTHOR]

The letter to the editor discusses the impact of CD34+ cell doses on outcomes in pediatric patients undergoing autologous hematopoietic stem cell transplant for central nervous system tumors (CNSTs) and high-risk neuroblastoma. The study found that higher CD34+ cell doses were associated with improved overall survival and progression-free survival in CNST patients but not in neuroblastoma patients. Possible explanations for these differences include tumor cell contamination, differences in the marrow microenvironment, and variations in chemosensitivity between the two conditions. Further research is needed to understand these outcome differences and optimize transplant outcomes for children with CNSTs and neuroblastoma. [Extracted from the article]

Angiogenesis is crucial for successful bone defect repair. Co‐transplanting Bone Marrow Stromal Cells (BMSCs) and Endothelial Cells (ECs) has shown promise for vascular augmentation, but it face challenges in hostile tissue microenvironments, including poor cell survival and limited efficacy. In this study, the mitochondria of human BMSCs are isolated and transplanted to BMSCs from the same batch and passage number (BMSCsmito). The transplanted mitochondria significantly boosted the ability of BMSCsmito‐ECs to promote angiogenesis, as assessed by in vitro tube formation and spheroid sprouting assays, as well as in vivo transplantation experiments in balb/c mouse and SD rat models. The Dll4‐Notch1 signaling pathway is found to play a key role in BMSCsmito‐induced endothelial tube formation. Co‐transplanting BMSCsmito with ECs in a rat cranial bone defect significantly improves functional vascular network formation, and improve bone repair outcomes. These findings thus highlight that mitochondrial transplantation, by acting through the DLL4‐Notch1 signaling pathway, represents a promising therapeutic strategy for enhancing angiogenesis and improving bone repair. Hence, mitochondrial transplantation to BMSCS as a therapeutic approach for promoting angiogenesis offers valuable insights and holds much promise for innovative regenerative medicine therapies. [ABSTRACT FROM AUTHOR]

Background: There is a need for therapies that can mitigate bone marrow dysfunction and organ toxicity that occur following myeloablative injury and reduced intensity conditioning regimens used in patients undergoing bone marrow transplantation (BMT). The pathogenesis of adverse effects from BMT conditioning has been linked to injury to the vascular endothelium, bone marrow (BM), and other organs. Objective: To evaluate the impact of the thrombopoietin mimetic drug JNJ-26366821 (TPOm) on BM vascular recovery in mice undergoing myeloablative radiation conditioning followed by BMT. Study design: TPOm (doses: 0 µg, 300 µg, 1000 µg per Kg body weight) was administered on Days 0 and 7 after BMT, in mice receiving a total body irradiation (TBI) conditioning regimen (5.5 Gy x 2) before congenic BMT. BM donner cell engraftment was analyzed using flow cytometry on Days 7, 14, and 30 post-BMT. The morphological and biophysical properties of the BM vasculature were evaluated by intravital multiphoton microscopy (MPM) and immunofluorescence confocal imaging. Herein, morphological properties involve microvascular density (MVD), vessel diameter, and vascular area, while biophysical properties include transfer rate (Ktrans) of contrast within the BM vascular niche, as well as the fractional volume (vec) of extracellular extravascular tissue (EES). Results: No significant difference in donor chimerism was observed at days 7, 14, and 30 post-BMT, between TPOm and PBS-treated mice. TPOm intervention improved BM vasculature regeneration in transplanted mice. The MVD, Ktrans, and BM vasculature as well as vascular endothelial growth factor receptor-2 (VEGFR2) in the BM, showed a dose dependent improvement inmice treated with TPOm. On day 14 post-BMT, the group receiving 1000 µg/Kg TPOm showed significant shifts (p-value < 0.05) in MVD, Ktrans, and VEGFR2 expression from their corresponding control types (TPOm dose 0 µg) towards levels comparable to healthy controls. Conclusion: TPOm intervention augments BM vascular structure and function, which may be important for hematopoietic recovery and bone marrow function in radiation conditioned hematopoietic stem cell transplant patients, in addition to enhancing platelet recovery. day 14 post-BMT, the group receiving 1000 µg/Kg TPOm showed significant shifts (p-value < 0.05) in MVD, Ktrans, and VEGFR2 expression from their corresponding control types (TPOm dose 0 µg) towards levels comparable to healthy controls. Conclusion: TPOm intervention augments BM vascular structure and function, which may be important for hematopoietic recovery and bone marrow function in radiation conditioned hematopoietic stem cell transplant patients, in addition to enhancing platelet recovery. [ABSTRACT FROM AUTHOR]

The letter to the editor discusses the use of Isavuconazole in treating invasive fungal disease in children with malignancy or undergoing cellular therapy. Isavuconazole is a pro-drug rapidly converted to an active drug that inhibits fungal enzyme synthesis. It has high bioavailability and is approved for treating aspergillosis and mucormycosis in adults. The study analyzed the use of Isavuconazole in pediatric hematology and oncology departments in Poland, showing promising outcomes in treating invasive fungal diseases. [Extracted from the article]

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, but the molecular mechanisms underlying IBD are incompletely understood. In this study, we explored the role and regulating mechanism of otubain 2 (OTUB2), a deubiquitinating enzyme, in IBD. Methods: To study the function of OTUB2 in IBD, we generated Otub2–/– mice and treated them with dextran sulfate sodium (DSS) to induce experimental colitis. Bone marrow transplantation was performed to identify the cell populations that were affected by OTUB2 in colitis. The molecular mechanism of OTUB2 in signal transduction was studied by various biochemical methods. Results: OTUB2 was highly expressed in colon‐infiltrating macrophages in both humans with IBD and mice with DSS‐induced experimental colitis. Colitis was significantly aggravated in Otub2–/– mice and bone marrow chimeric mice receiving Otub2–/– bone marrow. OTUB2‐deficiency impaired the production of cytokines and chemokines in macrophages in response to the NOD2 agonist muramyl dipeptide (MDP). Upon MDP stimulation, OTUB2 promoted NOD2 signaling by stabilizing RIPK2. Mechanistically, OTUB2 inhibited the proteasomal degradation of RIPK2 by removing K48‐linked polyubiquitination on RIPK2, which was mediated by the active C51 residue in OTUB2. In mice, OTUB2 ablation abolished the protective effects of MDP administration in colitis. Conclusion: This study identified OTUB2 as a novel regulator of intestinal inflammation. [ABSTRACT FROM AUTHOR]

Background Multiple myeloma is a hematologic malignancy that often responds to initial treatment with induction chemotherapy. Autologous stem cell transplantation is a common therapeutic approach post-remission, with bone marrow and peripheral blood stem cells (PBSC) being the primary sources. The optimal source for transplantation remains a subject of debate. This study aims to compare the efficacy and safety of autologous bone marrow transplantation (BMT) versus peripheral blood stem cell transplantation (PBSCT) after first remission induction in patients with multiple myeloma. Materials and Methods A total of 120 patients with multiple myeloma who achieved first remission after induction therapy were enrolled in this prospective study. They were randomly assigned to receive either autologous BMT (n=60) or PBSCT (n=60). Stem cell mobilization for the PBSCT group was performed using granulocyte-colony stimulating factor (G-CSF). The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included hematologic recovery time, incidence of transplant-related complications, and quality of life assessments. Data were analyzed using Kaplan-Meier survival analysis and log-rank tests. Results The median overall survival for the BMT group was 48 months, while the PBSCT group showed a median OS of 54 months (p=0.35). The median progression-free survival was 28 months for BMT and 32 months for PBSCT (p=0.27). Hematologic recovery was significantly faster in the PBSCT group, with a median neutrophil recovery time of 10 days compared to 15 days in the BMT group (p<0.01). The incidence of acute transplant-related complications was lower in the PBSCT group (15%) compared to the BMT group (25%), though this was not statistically significant (p=0.12). Quality of life assessments at 6 months post-transplant showed no significant difference between the two groups. Conclusion Both autologous BMT and PBSCT provide comparable overall and progression-free survival rates in multiple myeloma patients after first remission induction. However, PBSCT is associated with faster hematologic recovery and a trend towards fewer transplant-related complications, suggesting a potential preference for PBSCT in clinical practice. Further longterm studies are needed to fully elucidate the optimal transplantation approach. [ABSTRACT FROM AUTHOR]

Background: Despite being recognized as a safe procedure with minimal reported complications, injecting autologous bone marrow aspirate concentrate (BMAC) as an adjuvant to arthroscopic partial meniscectomy (APM) for symptomatic patients with meniscal tears and concomitant knee osteoarthritis (OA) has not been studied in randomized controlled trials. Purpose: To compare patient-reported outcome measure (PROM) scores and radiographic outcomes in symptomatic patients with meniscal tears and concomitant mild knee OA who underwent APM with and without an autologous BMAC injection administered at the time of surgery. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Enrolled patients aged ≥18 years determined to have a symptomatic meniscal tear with concomitant mild knee OA suitable for APM and meeting inclusion and exclusion criteria were randomized into 2 groups: BMAC and control (no BMAC). The primary endpoint of the study was the International Knee Documentation Committee (IKDC) score at 1 year postoperatively. Secondary endpoints included radiographic outcomes (Kellgren-Lawrence grade) at 1 year postoperatively and various PROM scores, including those for the IKDC, Knee injury and Osteoarthritis Outcome Score (KOOS), visual analog scale, and Veterans RAND 12-Item Health Survey, at 3 months, 6 months, 1 year, and 2 years after meniscectomy. Results: Of the 95 enrolled patients, 83 (87.4%) were included for final analysis. No significant differences were found between the groups with regard to patient characteristics, intraoperative variables, concomitant procedures, preoperative PROM scores, or preoperative radiographic findings. At 1 year postoperatively, the BMAC group failed to demonstrate significantly better IKDC scores (P =.687) or radiographic outcomes (P >.05 for all radiographic measures) compared with the control group. Secondary PROM scores also did not significantly differ between the groups (P >.05 for all PROMs). However, there were higher achievement rates of the minimal clinically important difference for the KOOS Sport (100.0% vs 80.0%, respectively; P =.023) and KOOS Symptoms (92.3% vs 68.0%, respectively; P =.038) at 1 year postoperatively in the BMAC group than in the control group. All PROMs, excluding the VR-12 mental score, showed significant improvements compared with baseline at all postoperative time points for both the BMAC and control groups. Conclusion: The addition of an autologous BMAC injection during APM did not result in significant changes in IKDC scores or radiographic outcomes at the 1-year postoperative mark. Secondary PROM scores were generally comparable between the 2 groups, but there was higher minimal clinically important difference achievement for the KOOS Sport and KOOS Symptoms at 1 year postoperatively in the BMAC group. In patients with symptoms consistent with a meniscal tear who had concomitant mild OA, the addition of BMAC to arthroscopic debridement did not affect the outcome. Registration: NCT02582489 (ClinicalTrials.gov) [ABSTRACT FROM AUTHOR]

The article in Clinical & Experimental Dermatology discusses a case of Hoyeraal–Hreidarsson syndrome (HHS) in a 15-year-old Egyptian girl with a new homozygous splice variant in the PARN gene. HHS is a disorder characterized by bone marrow failure, intrauterine growth restriction, developmental delay, cerebellar hypoplasia, and immunodeficiency. The study highlights the genetic and clinical features of telomere biology disorders (TBDs) and the challenges in diagnosing and treating these rare conditions. [Extracted from the article]

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a lifesaving treatment but carries a high infection risk. Diagnosing infections remains challenging due to the limited accuracy of standard biomarkers. Methods: This single-center study aimed to evaluate presepsin (PSP) and YKL-40 as infection biomarkers in febrile patients during the allo-HSCT pre-engraftment phase. Biomarker levels were prospectively measured in 61 febrile episodes from 54 allo-HSCT patients at admission, representing baseline levels, and then at Day 1, 3, 5, and 7 following fever onset. The diagnostic value was compared to that of procalcitonin (PCT). Results: PSP showed fair diagnostic value on Day 1 (AUC 0.656; 95% CI: 0.510–0.802) and Day 3 (AUC 0.698; 95% CI: 0.559–0.837). YKL-40 did not provide any significant diagnostic value across measured time points. PCT outperformed PSP and YKL-40, particularly on Day 3 (AUC 0.712; 95% CI: 0.572–0.852). When combining biomarkers, the best model for predicting infection used PSP > 3.144 ng/mL and PCT > 0.28 μg/L on Day 3, resulting in R2 of about 31% (p < 0.001). Conclusions: Neither test showed sufficient discriminative power for early infection to recommend their use as individual diagnostic tools in clinical practice. [ABSTRACT FROM AUTHOR]

ABO incompatibility does not hinder bone marrow transplantation (BMT), but it has been associated with worse outcomes and additional adverse events. This study aimed to verify the impact of incompatible red blood cells (iRBCs) in allogeneic BMT and to determine a safe number of iRBCs to be infused. We compared ABO-incompatible (iABO) allogeneic BMT (n = 42) with ABO-compatible allogeneic BMT (n = 44) and evaluated the impact of the number of infused iRBCs on outcomes and adverse events. The iABO patients demonstrated delayed time to transfusion independence at 30 days and 60 days, increased requirement for red blood cell (RBC) transfusion and greater hemolysis signals and incidence of pure red cell aplasia. Neutrophil/platelet engraftment, length of hospitalization post-transplant, platelet units required, graft-versus-host disease occurrence and overall survival were similar in both groups. Patients in the iABO group received 1.03 × 1010 iRBCs/kg (range, 0.36–3.88). Infusion of iRBCs >1.0 × 1010 /kg was related to graft failure or death before neutrophil engraftment or platelet engraftment or both as well as increased plasma requirement and increased creatinine. Our results also suggest that antibody titers impact the transplantation scenario. The iABO transplantation showed some unfavorable outcomes. It is important to monitor the value of iRBCs to be infused, considering the recipient antibody titers. We propose using the number of iRBCs (iRBCs/kg) as a dose parameter with regard to infused iRBCs. Further studies are necessary to clarify the maximum safe number of iRBCs in iABO transplants. [ABSTRACT FROM AUTHOR]

Purpose: Lipidomics is an important tool for triaging exposed individuals, and helps early adoption of prevention and control strategies. The purpose of this study was to screen significantly perturbed lipids between pre- and post-irradiation of human plasma samples after total body irradiation (TBI) and explore potential radiation biomarkers for early radiation classification. Methods: Plasma samples were collected before and after irradiation from 22 hospitalized cases of acute myeloid leukemia (AML) prepared for bone marrow transplantation. Acute total-body γ irradiation was performed at doses of 0, 4, 8, and 12 Gy. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) with multiple reaction monitoring (MRM) method was utilized. Self-paired studies before and after irradiation were performed to screen potential lipid categorization markers and markers of dose-response relationships for radiation perturbation in humans. Based on the screened potential markers, a human TBI dose estimation model was developed. Results: In total, 426 individual lipids from 14 major classes were quantified and 152 potential biomarkers with categorical characteristics were screened. A total of 80 lipids (32 TGs, 29 SMs, 9 FAs, 5 CEs, 5 PIs) were upregulated at 4 Gy, and a total of 91 lipids (39 SMs, 18 TGs, 15 HexCers, 7 CEs, 6 Cers, 3 LacCers, 2 LPEs, 1 PI) were upregulated at 12 Gy. Comparison of the ROC curves between the non-exposed and exposed groups at different doses showed AUC values ranging from 0.807 to 0.876. The metabolic pathways of potential lipid markers are mainly sphingolipid and glycerolipid metabolism, unsaturated fatty acid biosynthesis, fatty acid degradation and biosynthesis. Among the 13 dose-dependent radiosensitive lipids, CE (20:5), CE (18:1) and PI (18:2/18:2) were gradually incorporated into the TBI dose estimation model. Conclusion: This study suggested that it was feasible to acquire quantitative lipid biomarker panels using targeted lipidomics platforms for rapid, high-throughput triage. Lipidomics strategies for radiation biodosimetry in humans were established with lipid biomarkers with good dose-response relationship. [ABSTRACT FROM AUTHOR]

After September 11, 2001, nuclear threat prompted government agencies to develop medical countermeasures to mitigate two syndromes, the hematopoietic-acute radiation syndrome (H-ARS) and the higher-dose gastrointestinal-acute radiation syndrome (GI-ARS), both lethal within weeks. While repurposing leukemia drugs that enhance bone marrow repopulation successfully treats H-ARS, no mitigator potentially deliverable under mass casualty conditions preserves the GI tract. We recently reported that anti-ceramide single-chain variable fragment (scFv) mitigates GI-ARS lethality, abrogating ongoing small intestinal endothelial apoptosis to rescue Lgr5+ stem cells. Here, we examine long-term consequences of prevention of acute GI-ARS lethality. For these studies, C57BL/6J male mice were treated with 15 Gy whole body irradiation, the 90% GI-ARS lethal dose for this mouse strain. Mice irradiated with 15 Gy alone or with 15 Gy + bone marrow transplantation (BMT) or anti-ceramide scFv, succumb to an ARS within 8 to 10 days. Autopsies reveal only mice receiving anti-ceramide scFv at 24 hours post-whole body irradiation display small intestinal rescue. No marrow reconstitution occurs in any group with attendant undetectable circulating blood elements. Mice receiving 15 Gy + BMT + scFv, however, normalize blood counts by day 12, suggesting that scFv also improves marrow reconstitution, a concept for which we provide experimental support. We show that at 14 Gy, the upper limit dose for H-ARS lethality before transition to GI-ARS lethality, anti-ceramide scFv markedly improves marrow take, reducing the quantity of marrow-conferring survival by more than 3-fold. Consistent with these findings, mice receiving 15 Gy + BMT + scFv exhibit prolonged survival. At day 90, before sacrifice, they display normal appearance, behavior, and serum biochemistries, and surprisingly, at full autopsy, near-normal physiology in all 42 tissues examined. Anti-ceramide scFv mitigates GI-ARS lethality and improves marrow reconstitution rendering prolonged survival with near normal autopsies. [ABSTRACT FROM AUTHOR]

Loss and overexpression of FAT1 occurs among different cancers, with these divergent states equated with tumor suppressor and oncogene activity, respectively. Regarding the latter, FAT1 is highly expressed in a high proportion of human acute leukemias relative to normal blood cells, with evidence pointing to an oncogenic role. We hypothesized that this occurrence represents legacy expression of FAT1 in undefined hematopoietic precursor subsets (i.e. sustained following transformation), predicating a role for FAT1 during normal hematopoiesis. We explored this concept by using the Vav-iCre strain to construct conditional knockout mice in which Fat1 expression was deleted at the hematopoietic stem cell stage. Extensive analysis of precursor and mature blood populations using multipanel flow cytometry revealed no ostensible differences between Fat1 conditional knockout mice and normal littermates. Further functional comparisons involving colony-forming unit and competitive bone marrow transplantation assays support the conclusion that Fat1 is dispensable for normal murine hematopoiesis. [ABSTRACT FROM AUTHOR]

Angiotensin-converting enzyme 2 (ACE2), a crucial element of the renin-angiotensin system (RAS), metabolizes angiotensin II into Ang (1–7), which then combines with the Mas receptor (MasR) to fulfill its protective role in various diseases. Nevertheless, the involvement of ACE2 in sepsis-induced cardiomyopathy (SIC) is still unexplored. In this study, our results revealed that CLP surgery dramatically impaired cardiac function accompanied with disruption of the balance between ACE2-Ang (1–7) and ACE-Ang II axis in septic heart tissues. Moreover, ACE2 knockin markedly alleviated sepsis induced RAS disorder, cardiac dysfunction and improved survival rate in mice, while ACE2 knockout significantly exacerbates these outcomes. Adoptive transfer of bone marrow cells and in vitro experiments showed the positive role of myeloid ACE2 by mitigating oxidative stress, inflammatory response, macrophage polarization and cardiomyocyte apoptosis by blocking NF-κB and STAT1 signals. However, the beneficial impacts were nullified by MasR antagonist A779. Collectively, these findings showed that ACE2 alleviated SIC by inhibiting M1 macrophage via activating the Ang (1–7)-MasR axis, highlight that ACE2 might be a promising target for the management of sepsis and SIC patients. [ABSTRACT FROM AUTHOR]

T cell senescence alters the homeostasis of distinct T cell populations and results in decayed adaptive immune protection in older individuals, but a link between aging and dynamic T cell clone changes has not been made. Here, using a newly developed computational framework, Repertoire Functional Units (RFU), we investigate over 6500 publicly available TCR repertoire sequencing samples from multiple human cohorts and identify age-associated RFUs consistently across different cohorts. Quantification of RFU reduction with aging reveals accelerated loss under immunosuppressive conditions. Systematic analysis of age-associated RFUs in clinical samples manifests a potential link between these RFUs and improved clinical outcomes, such as lower ICU admission and reduced risk of complications, during acute viral infections. Finally, patients receiving bone marrow transplantation show a secondary expansion of the age-associated clones upon stem cell transfer from younger donors. Together, our results suggest the existence of a 'TCR clock' that could reflect the immune functions in aging populations. Immune aging is associated with altered homeostasis of distinct T cell populations, but a link to clonal dynamic is still not made. Here the authors develop a new framework, Repertoire Functional Units (RFU), and use public TCR sequences to find specific TCR clonal changes that correlate with aged immune repertoires or outcomes of acute viral infection. [ABSTRACT FROM AUTHOR]

Salivary gland dysfunction is a common side effect of cancer treatments. Salivary function plays key roles in critical daily activities. Consequently, changes in salivary function can profoundly impair quality of life for cancer patients. We discuss salivary gland anatomy and physiology to understand how anticancer therapies such as chemotherapy, bone marrow transplantation, immunotherapy, and radiation therapy impair salivary function. We discuss approaches to quantify xerostomia in the clinic, including the advantages and limitations of validated quality-of-life instruments and approaches to directly measuring salivary function. Current and emerging approaches to treat cancer therapy-induced dry mouth are presented using radiation-induced salivary dysfunction as a model. Limitations of current sialagogues and salivary analogues are presented. Emerging approaches, including cellular and gene therapy and novel pharmacologic approaches, are described. [ABSTRACT FROM AUTHOR]

The document is a schedule of events for the Andrology conference happening in September 2024. The conference covers a wide range of topics related to male reproductive health, including fertility preservation, genetics of male germ cells, transgender and gender diverse persons, and the treatment of erectile dysfunction. Experts from different countries will be presenting their research and insights in various sessions and symposiums. The document provides a comprehensive overview of the presentations and symposiums that will take place at the conference. [Extracted from the article]

Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) syndrome is a rare primary immunodeficiency disease in humans caused by a gain of function in CXCR4, mostly due to inherited heterozygous mutations in CXCR4. One major clinical symptom of WHIM patients is their high susceptibility to human papillomavirus (HPV) induced disease, such as warts. Persistent high risk HPV infections cause 5% of all human cancers, including cervical, anogenital, head and neck and some skin cancers. WHIM mice bearing the same mutation identified in WHIM patients were created to study the underlying causes for the symptoms manifest in patients suffering from the WHIM syndrome. Using murine papillomavirus (MmuPV1) as an infection model in mice for HPV-induced disease, we demonstrate that WHIM mice are more susceptible to MmuPV1-induced warts (papillomas) compared to wild type mice. Namely, the incidence of papillomas is higher in WHIM mice compared to wild type mice when mice are exposed to low doses of MmuPV1. MmuPV1 infection facilitated both myeloid and lymphoid cell mobilization in the blood of wild type mice but not in WHIM mice. Higher incidence and larger size of papillomas in WHIM mice correlated with lower abundance of infiltrating T cells within the papillomas. Finally, we demonstrate that transplantation of bone marrow from wild type mice into WHIM mice normalized the incidence and size of papillomas, consistent with the WHIM mutation in hematopoietic cells contributing to higher susceptibility of WHIM mice to MmuPV1-induced disease. Our results provide evidence that MmuPV1 infection in WHIM mice is a powerful preclinical infectious model to investigate treatment options for alleviating papillomavirus infections in WHIM syndrome. Author summary: Mice carrying the same gain-of-function mutation in the gene CXCR4 that is present in human patients suffering from the Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) syndrome were previously created to understand the biology underlying this syndrome and to develop better means for treating WHIM patients. WHIM mice display neutropenia and lymphopenia symptoms as do WHIM patients. One of the key features of the WHIM syndrome in humans is increased susceptibility to infections by human papillomaviruses (HPV) with the majority of WHIM patients experiencing persistent warts and some developing anogenital cancers, both caused by HPVs. In this study we use a mouse papillomavirus, MmuPV1, which is a model for HPV infection in humans, to ask if the WHIM mice are more susceptible to infection and to understand why. We demonstrate that WHIM mice are more susceptible to MmuPV1-induced disease and that correcting the neutropenia and lymphopenia by bone marrow transplantation was effective at decreasing susceptibility to MmuPV1 induced disease. Our data support WHIM mice as a disease model for WHIM syndrome for future investigations on curative treatment options. [ABSTRACT FROM AUTHOR]

Background Many patients with hematological malignancy develop fever after chemotherapy/conditioning but before chemotherapy-induced neutropenia (preneutropenic fever [PNF]). The proportion of PNF with an infectious etiology is not well established. Methods We conducted a single-center, prospective observational substudy of PNF (neutrophils >0.5 cells/μL, ≥38.0°C) in adults receiving acute myeloid leukemia (AML) chemotherapy, or allogeneic hematopoietic cell transplant (allo-HCT) conditioning enrolled in a neutropenic fever randomized controlled trial between 1 January and 31 October 2018. Eligible patients had anticipated neutropenia ≥10 days and exclusions included concurrent infection and/or neutropenia prior to chemotherapy or conditioning. PNF rates and infections encountered were described. Associations between noninfectious etiologies and fever were explored. Antimicrobial therapy prescription across preneutropenic and neutropenic periods was examined. Results Of 62 consecutive patients included (43 allo-HCT, 19 AML), 27 had PNF (44%) and 5 (19%) had an infective cause. Among allo-HCT, PNF occurred in 14 of 17 (82%) who received thymoglobulin; only 1 of 14 (7%) had infection. During AML chemotherapy, 18 of 19 received cytarabine, of which 8 of 18 (44%) had PNF and 3 of 8 (38%) had infection. Most patients with PNF had antimicrobial therapy continued into the neutropenic period (19/27 [70%]). Those with PNF were more likely to be escalated to broader antimicrobial therapy at onset/during neutropenic fever (5/24 [21%] vs 2/30 [7%]). Conclusions Rates of PNF were high, and documented infection low, leading to prolonged and escalating antimicrobial therapy. In the absence of infection, early cessation of empiric therapy after PNF is recommended as an important stewardship intervention. [ABSTRACT FROM AUTHOR]

Objective and Background: Sinusoidal obstruction syndrome (SOS) is a life‐threatening complication in hematopoietic stem cell transplantation (HSCT) patients. However, the related risk factors in pediatric and young adult HSCT recipients remain unclear. Thus, we conducted this meta‐analysis to identify potential risk factors for SOS in children and young adults undergoing HSCT. Method: We acquired related articles through searching PubMed, EMBASE, and the Cochrane Library up to May 31, 2024. We calculated odds ratios (ORs) and corresponding 95% confidence intervals (CIs) to identify potential risk factors. Results: A total of 12 studies with 7644 HSCT recipients were included. Bone marrow transplantation (OR = 1.35, 95% CI: 1.03–1.77, I2 = 0%), busulfan (BU) (OR = 3.63, 95% CI: 1.78–7.38, I2 = 70%), and fludarabine (FLU) (OR = 1.55, 95% CI: 1.09–2.21, I2 = 16%) were risk factors for SOS after HSCT in children and young adults. Conclusion: Bone marrow transplantation and the use of BU or FLU might be risk factors for SOS after HSCT in children and young adults. [ABSTRACT FROM AUTHOR]

The system of nitric oxide synthases (NOSs) is comprised of three isoforms: nNOS, iNOS, and eNOS. The roles of NOSs in respiratory diseases in vivo have been studied by using inhibitors of NOSs and NOS-knockout mice. Their exact roles remain uncertain, however, because of the non-specificity of inhibitors of NOSs and compensatory up-regulation of other NOSs in NOS-KO mice. We addressed this point in our triple-n/i/eNOSs-KO mice. Triple-n/i/eNOSs-KO mice spontaneously developed pulmonary emphysema and displayed exacerbation of bleomycin-induced pulmonary fibrosis as compared with wild-type (WT) mice. Triple-n/i/eNOSs-KO mice exhibited worsening of hypoxic pulmonary hypertension (PH), which was reversed by treatment with sodium nitrate, and WT mice that underwent triple-n/i/eNOSs-KO bone marrow transplantation (BMT) also showed aggravation of hypoxic PH compared with those that underwent WT BMT. Conversely, ovalbumin-evoked asthma was milder in triple-n/i/eNOSs-KO than WT mice. These results suggest that the roles of NOSs are different in different pathologic states, even in the same respiratory diseases, indicating the diversity of the roles of NOSs. In this review, we describe these previous studies and discuss the roles of NOSs in respiratory health and disease. We also explain the current state of development of inorganic nitrate as a new drug for respiratory diseases. [ABSTRACT FROM AUTHOR]

Sinusoidal obstruction syndrome/veno‐occlusive disease (SOS/VOD) is a life‐threatening complication which can develop after haemopoietic stem cell transplantation (HSCT) and some antibody–drug conjugates. Several SOS/VOD diagnostic and management guidelines exist, with the most recent and refined being the European Society for Blood and Marrow Transplantation adult and paediatric guidelines. Timely diagnosis and effective management (including the availability of therapeutic options) significantly contribute to improved patient outcomes. In Australia and New Zealand, there is variability in clinical practice and access to SOS/VOD therapies. This review aims to summarise the current evidence for SOS/VOD diagnosis, prevention and treatment and to provide recommendations for SOS/VOD in the context of contemporary Australasian HSCT clinical practice. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a widely utilized treatment for various hematological diseases. While selection criteria for unrelated donors are well established, there is a lack of consistency and standardization in the selection of related donors. This study investigated the current approach of hematologists to the selection of related donors at Turkish HSCT centers. The study employed a cross-sectional survey design, distributing a self-administered questionnaire to 95 adult and pediatric transplantation centers in Türkiye to investigate their approaches to related donor selection for allo-HSCT. The questionnaire collected data on various topics including the center's experience in performing allo-HSCT, patient groups treated, number of allo-HSCT procedures conducted between 2015 and 2021, preferences for related donors, considerations in related donor selection (such as sex and past pregnancies), guidelines utilized for related donor selection, upper age limit for related donors, and the use of specialized advanced analyses for elderly donors. The response rate to the survey was 38.9%. Variability was observed across centers in terms of sex consideration and the impact of past pregnancies on related female donor rejection. Different guidelines were employed for related donor selection, with the European Bone Marrow Transplantation guidelines being the most commonly used. Regarding the upper age limit for related donors, 8.1% of centers accepted an upper age limit of 55 years, 48.7% preferred an upper age limit of 65 years, and 43.2% selected related donors aged 65 and above. The lack of standardized guidelines for related donor selection in HSCT centers leads to variability in criteria and potential risks. Collaboration among centers is essential to establish consensus and develop standardized protocols. [ABSTRACT FROM AUTHOR]

To reduce the risk of nonunion after spinal fusion surgery, the in situ transplantation of bone marrow mesenchymal stem cells (BMSCs) induced toward osteogenic differentiation by bone morphogenetic protein-2 (BMP2) has been proven effective. However, the current biological agents used for transplantation have limitations, such as a short half-life and low bioavailability. To address this, our study utilized a safe and effective gelatin-methacryloyl (GelMA) as a carrier for BMP2. In vitro, experiments were conducted to observe the ability of this composite vehicle to induce osteogenic differentiation of BMSCs. The results showed that the GelMA hydrogel, with its critical properties and controlled release performance of BMP2, exhibited a slow release of BMP2 over 30 days. Moreover, the GelMA hydrogel not only enhanced the proliferation activity of BMSCs but also significantly promoted their osteogenic differentiation ability, surpassing the BMP2 effects. To investigate the potential of the GelMA-BMP2 composite vehicle, a rabbit model was employed to explore its ability to induce in situ intervertebral fusion by BMSCs. Transplantation experiments in rabbits demonstrated the effective induction of intervertebral bone fusion by the GelMA-BMP2-BMSC composite vehicle. In conclusion, the GelMA-BMP2-BMSC composite vehicle shows promising prospects in preclinical translational therapy for spinal intervertebral fusion. It addresses the limitations of current biological agents and offers a controlled release of BMP2, enhancing the proliferation and osteogenic differentiation of BMSCs. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To measure baseline work gratitude among nurses and staff on a blood and marrow transplantation unit; to evaluate the impact of a positive workplace recognition intervention on work gratitude, sense of belonging and community, and job satisfaction; and to explore the relationships among these variables and job satisfaction. SAMPLE & SETTING: In total, 40 survey responses (preintervention =24, postintervention = 16) were collected from nurses and staff on a blood and marrow transplantation unit at a large academic hospital. METHODS & VARIABLES: A pre- and postintervention survey included a demographic questionnaire and the Work Gratitude Scale. Publicfacing digital signage was installed and used to project positive recognition, including expressions of gratitude from patients and staff. RESULTS: Those with higher job satisfaction and a stronger sense of belonging and community reported higher work gratitude scores. There were no significant changes in job satisfaction, sense of belonging and community, and work gratitude scores. IMPLICATIONS FOR NURSING: Creating a positive work environment through gratitude and positive recognition could increase job satisfaction and sense of belonging and community among nurses and staff. [ABSTRACT FROM AUTHOR]

The diagnosis of cancer or cardiac abnormalities in infants is often associated with prolonged hospitalization, which can negatively impact caregiver-child bonding due to separation, medical stressors, and changes in the caregiving role. The purpose of this study was to pilot an interdisciplinary psychosocial intervention including songwriting, an expressive journal and activity book, and a bonding assessment. Interventions were facilitated by a board-certified music therapist and Certified Child Life Specialist. A total of 15 families completed the pretest, four intervention sessions, and post intervention test. Quantitative data suggest increased caregiver–child bonding and increased caregiver confidence. Caregivers reported high levels of satisfaction with the intervention in qualitative responses. In summary, results from this pilot study lay the groundwork for a future larger-scale evaluation. [ABSTRACT FROM AUTHOR]

Context Children with cancer are at risk of poor nutritional status during treatment and into survivorship. Objectively measured taste perception and self-reported food hedonics are 2 factors that may influence food intake. Objective This 2-armed systematic review examined whether chemotherapy and radiotherapy affect (1) taste perception and (2) hedonic experiences of children and survivors of childhood cancer. Data Source A 2-armed systematic literature search was conducted in the Medline, CINAHL, Embase, and PsychInfo database until June 2022. The effects of cancer treatment on objective taste perception or food hedonics (ie, food liking or aversion and appetite) were examined. Data Extraction Peer-reviewed articles published in English of studies that included children (aged <18 years) or survivors of childhood cancer (any age) were reviewed. Risk of bias was determined using the Evidence Analysis Library by the Academy of Nutrition and Dietetics. Data Analysis A total of 1417 articles in the taste search arm and 3862 articles in the hedonics search arm were identified. Of these, 9 and 4 articles were eligible for review, respectively. Cancer treatment had highly variable effects on taste perception during treatment and into survivorship. Learned food aversions were experienced by children receiving chemotherapy treatment and liking of meats and salty foods by children with cancer was affected. The impact of treatment on appetite varied. Conclusions Cancer treatment did not uniformly affect taste perception. Food liking may be negatively affected, and learned food aversions may develop during cancer treatment. To establish the clinical relevance of childhood cancer treatment on taste perception and food hedonics, more research is required. Systematic Review Registration PROSPERO registration no.CRD42020207127. [ABSTRACT FROM AUTHOR]

Background: Graft‐versus‐host disease (GVHD) is a recognized complication among individuals undergoing bone marrow transplantation (BMT). There is a requirement for supplementary data regarding the in‐patient outcomes of GVHD in individuals who have undergone BMT. Our analysis seeks to assess the healthcare burden and outcomes associated with GVHD in hospitalized patients who have undergone BMT. Method: In this retrospective study, we used data from the National Inpatient Sample (NIS) database spanning from 2016 to 2019. Utilizing ICD‐10 codes, we distinguished hospitalizations related to BMT and grouped them into two categories: those with GVHD and those without GVHD. Our areas of focus included in‐hospital mortality, length of stay, charges, and associations related to GVHD. Unadjusted odds ratios/coefficients were computed through univariable analysis, followed by adjusted odds ratios (aORs)/coefficients from multivariable analysis that considered potential confounding factors. Results: From 2016 to 2019, data were collected from 13,999 hospitalizations with bone marrow transplants. Among them, 836 had GVHD cases. Patient characteristics showed slight differences in mean age and demographics between the two groups, with GVHD patients having a mean age of 51.61 years and higher percentages of males and whites. Analyzing outcomes, patients with GVHD experienced significantly longer hospital stays (41.4 days vs. 21.3 days) and higher total hospital charges ($824,058 vs. $335,765). Adjusting for confounding factors, GVHD posed a substantial risk. The aOR for mortality in GVHD hospitalizations was 7.20 (95% CI: 5.54–9.36, p <.001). The coefficient for the length of stay was 19.36 days (95% CI: 17.29–21.42, p <.001), and the coefficient for total hospital charges was $453,733 (95% CI: $396,577 to $510,889, p <.001) in GVHD cases. Furthermore, GVHD in patients was associated with elevated risks of various medical conditions. The aORs for sepsis, pneumonia, acute respiratory failure, intubation and mechanical ventilation, Clostridium difficile infection, and acute kidney injury (AKI) in GVHD patients were 2.79 (95% CI: 2.28–3.41, p <.001), 3.30 (95% CI: 2.57–4.24, p <.001), 5.10 (95% CI: 4.01–6.49, p <.001), 4.88 (95% CI: 3.75–6.34, p <.001), 1.45 (95% CI: 1.13–1.86, p =.003), and 3.57 (95% CI: 2.97–4.29, p <.001). Conclusion: GVHD in individuals undergoing BMT is linked to elevated mortality rates, prolonged hospitalization, and higher healthcare costs. Moreover, they face a significantly increased risk of developing complications, such as sepsis, pneumonia, acute respiratory failure, C. difficile infection, and AKI. These results underscore the critical need for vigilant monitoring and effective GVHD management to improve patient outcomes and reduce the complications associated with BMT. Nevertheless, further prospective studies are essential to obtain a more profound understanding and a comprehensive assessment of outcomes in these hospitalized patients. [ABSTRACT FROM AUTHOR]

Purpose of Review: Given the poor outcomes for peripheral T-cell lymphomas (PTCL), stem cell transplant (SCT) remains an important therapeutic approach. Post-SCT relapse is common and maintenance therapy post-SCT is increasingly being utilized. Here we review the use of post-SCT maintenance therapy for PTCL patients. Recent Findings: Maintenance therapy is increasingly utilized to decrease post-SCT relapse and improve outcomes in PTCL. Ongoing and completed post-SCT maintenance trials utilizing agents such as romidepsin, brentuximab vedotin, duvelisib, and pembrolizumab have shown efficacy in decreasing relapse. Further, additional agents with efficacy in PTCL have emerged that may inform future maintenance approaches. Summary: Maintenance therapy is a promising approach to maintain response after SCT in PTCL. While several trials are ongoing to evaluate maintenance therapy in PTCL, current data suggests this may be an effective method to decrease post-SCT relapse. [ABSTRACT FROM AUTHOR]

Abstract Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for several malignant and non-malignant hematologic conditions. However, patients undergoing HSCT are at increased risk of developing serious cardiovascular events. Whether cardiovascular risks differ by the type of transplantation strategy used, allogeneic versus autologous HSCT, is unknown. Leveraging the National Inpatient Sample (2016–2019), we assessed the incidence of early cardiovascular events by HSCT mode (allogeneic vs autologous). The primary outcome was the incidence of atrial fibrillation (AF). The secondary outcome was the occurrence of any major adverse cardiac events (MACE), defined as acute heart failure, myocardial infarction (MI), symptomatic atrial or ventricular arrhythmia or heart block, and cardiovascular death. Outcomes were compared between those undergoing allogeneic versus autologous HSCT. Multivariable regression, adjusting for cardiovascular and cancer-related factors, was used to define the association between pre-HSCT factors and MACE. We further assessed the effect of acute cardiovascular events on in-patient mortality by calculating adjusted odds ratio (aOR) with corresponding 95% confidence intervals (CI) and p-values. Overall, 64,705 weighted hospitalizations for HSCT were identified, of which 22,655 (35.0%) were allogeneic HSCT and 42,050 (65.0%) were autologous HSCT. The prevalence of AF was 9.1%, and 12.1% for any arrhythmia. In multivariable regression, allogeneic HSCT was associated with higher adjusted odds of peri-HSCT acute heart failure (aOR 2.64; 1.86–3.76; p

Introduction: Umbilical cord blood is an alternative source of hematopoietic progenitor cells for bone marrow transplantation; however, it is associated with a higher graft failure rate. The presence of a high rate of nucleated red blood cells (NRBCs) seems to be related to a greater capacity for engraftment, although is also associated with fetal distress conditions. We analyzed the correlation of the NRBC with quality parameters and its association with the utilization score of a cord blood unit. Study design and method: Data of 3346 units collected in a public cord blood bank from May 2010 to December 2017 were analyzed, retrospectively, to identify factors associated with an increased number of nucleated red blood cells and its correlation with the engraftment capacity measured through total nucleated cells (TNCs) and CD34 positive cells. We also evaluated the utilization score of these units and identified an NRBC cutoff associated with a higher score. Results: The median volume collected was 104 mL (42–255), the pre-processing TNC count was 144.77 × 107 (95.46–477.18), the post-processing TNC count was 119.44 × 107 (42.7–477.18), the CD34 count was 4.67 × 106 (0.31–48.01), the NRBC count was 5 (0–202) and the utilization score was 0.0228 (0.00143–0.9740). The NRBC showed a correlation with the collected volume, TNC and CD34 positive cells and a higher utilization score and the receiver operating characteristic (ROC) curve analysis identified the five NRBC/100 leukocytes cutoff that correlates better with the probability of use. No association with pathological conditions and the NRBC rate was observed. Conclusions: The NRBC is a feasible parameter for the screening of the cord blood unit (CBU) and the minimum cutoff of five NRBC/100 leukocytes can be a strategy in conjunction with the TNC to identify better units for cord blood bank sustainability.

Introduction: The time elapsed from diagnosis to hematopoietic stem cell transplantation (HSCT) is influenced by numerous factors. In Brazil, patients using the public health system are also dependent on the availability of HSCT-specific beds in the hematology ward. Objective and Methods: We conducted a cohort study of listed patients who underwent allogeneic HSCT at a Brazilian public hospital to investigate the impact of the waitlist time on post-HSCT survival. Results: The median time from diagnosis to HSCT was 19 months (IQR, 10 - 43), of which 6 months (IQR, 3 - 9) were spent on the waitlist. The time on the waitlist for HSCT appeared to influence mainly the survival of adult patients (≥ 18 years), with an increasing risk according to this time (RR, 3.53 and 95%CI, 1.81 - 6.88 for > 3 and ≤ 6 months; RR 5.86 and 95%CI, 3.26 - 10.53 for > 6 and ≤ 12 months, and; RR 4.24 and 95%CI, 2.32 - 7.75 for > 12 months). Conclusion: Patients who remained on the waitlist for less than 3 months had the highest survival (median survival, 856 days; IQR, 131 - 1607). The risk of reduced survival was about 6-fold higher (95%CI, 2.8 - 11.5) in patients with malignancies.

Donor lymphocyte infusions (DLIs) are often recommended products after allogeneic hematopoietic stem cell transplant to increase graft – versus – leukemia effect. More success rate of DLI has been reported in relapsed posttransplant chronic myeloid leukemia. Whatever the indication for DLI, mortality related to post-DLI infusion is 5%–20%, and more than one-third of patients will develop acute and/or chronic graft versus host disease (GVHD) after DLI. We report two cases where DLIs were used for residual disease after posttransplant. Both of DLI went uneventful. None of the patient’s developed signs of GVHD postinfusion. Although both patients expired with different causes, none were related to DLI infusion. Information from published literature suggests that DLI should be administered early after relapse or as a prophylactic strategy in patients receiving T-cell-depleted grafts, and patients with aggressive diseases may benefit from disease reduction before DLI. However, further evidence is required to evaluate its efficacy, especially in relapsed or residual hematological malignancies.

Background: Cognitive dysfunction caused by infection frequently emerges as a complication in sepsis survivor patients. However, a comprehensive understanding of its pathogenesis remains elusive. Methods: In our in vivo experiments, an animal model of endotoxemia was employed, utilizing the Novel Object Recognition Test and Morris Water Maze Test to assess cognitive function. Various techniques, including immunofluorescent staining, Western blotting, blood‒brain barrier permeability assessment, Limulus Amebocyte Lysate (LAL) assay, and Proximity-ligation assay, were employed to identify brain pathological injury and neuroinflammation. To discern the role of Caspase-11 (Casp11) in hematopoietic or non-hematopoietic cells in endotoxemia-induced cognitive decline, bone marrow chimeras were generated through bone marrow transplantation (BMT) using wild-type (WT) and Casp11-deficient mice. In vitro studies involved treating BV2 cells with E. coli-derived outer membrane vesicles to mimic in vivo conditions. Results: Our findings indicate that the deficiency of Casp11-GSDMD signaling pathways reverses infection-induced cognitive dysfunction. Moreover, cognitive dysfunction can be ameliorated by blocking the IL-1 effect. Mechanistically, the absence of Casp11 signaling significantly mitigated blood‒brain barrier leakage, microglial activation, and synaptic damage in the hippocampal CA3 region, ultimately leading to improved cognitive function. Conclusion: This study unveils the crucial contribution of Casp11 and GSDMD to cognitive impairments and spatial memory loss in a murine sepsis model. Targeting Casp11 signaling emerges as a promising strategy for preventing or treating cognitive dysfunction in patients with severe infections. [ABSTRACT FROM AUTHOR]

This letter to the editor discusses a survey conducted in Japan to study sun protection behaviors among adult survivors receiving hematopoietic cell transplantation (HCT). The study found that 83.1% of HCT survivors practiced some form of sun protection behavior, such as using sunscreen or wearing protective clothing. The prevalence of sun protection behaviors among HCT survivors in Japan was higher than in the general population. The letter emphasizes the importance of sun protection for HCT survivors, as sun exposure can worsen skin complications and increase the risk of skin cancers. The authors suggest that long-term follow-up clinics in HCT centers in Japan contribute to the higher prevalence of sun protection behaviors among HCT survivors. The study included 89 patients with a median age of 55 years, and the majority were male with acute myelogenous leukemia. The most common type of HCT was allogeneic unrelated cord blood transplantation. The study found that while the majority of survivors practiced sun protection, the use of sunscreen decreased significantly in survivors more than 5 years after HCT. The study highlights the importance of long-term attention to sun exposure and protection behaviors to reduce the risk of complications. [Extracted from the article]

Luminescent technology based on the luciferin–luciferase reaction has been extensively employed across various disciplines as a quantitative imaging modality. Owing to its non-invasive imaging capacity, it has evolved as a valuable in vivo bioimaging tool, particularly in small animal models in fields such as gene and cell therapies. We have previously successfully generated rats with a systemic expression of the luciferase gene at the Rosa26 locus. In this study, we transplanted bone marrow from these rats into micro-mini pigs and used in vivo imaging to non-invasively analyze the dynamics of the transplanted cells. In addition, we established that the rat-to-pig transplantation system is a discordant system, similar to the pig-to-human transplantation system. Thus, rat-to-pig transplantation may provide a clinically appropriate large animal model for pig-to-human xenotransplantation. [ABSTRACT FROM AUTHOR]

Gamma delta (γδ) T cells represent a minor fraction of human T cell repertoire but play an important role in mediating anti-infectious and anti-tumorous effects in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We performed a prospective study to analyze the effect of different transplant modalities on immune reconstitution of γδ T cells and subsets. CD3, CD4 and CD8 T cells were analyzed in parallel. Secondly, we examined the impact of γδ T cell reconstitution on clinical outcomes including acute Graft-versus-Host-Disease (aGvHD) and viral infections. Our cohort includes 49 pediatric patients who received unmanipulated bone marrow grafts from matched unrelated (MUD) or matched related (MRD) donors. The cohort includes patients with malignant as well as non-malignant diseases. Cell counts were measured using flow cytometry at 15, 30, 60, 100, 180 and 240 days after transplantation. Cells were stained for CD3, CD4, CD8, CD45, TCRαβ, TCRγδ, TCRVδ1, TCRVδ2, HLA-DR and combinations. Patients with a MRD showed significantly higher Vδ2+ T cells than those with MUD at timepoints +30, +60, +100 (p<0.001, respectively) and +180 (p<0.01) in univariate analysis. These results remained significant in multivariate analysis. Patients recovering with a high relative abundance of total γδ T cells and Vδ2+ T cells had a significantly lower cumulative incidence of grade II-IV aGvHD after transplantation (p=0.03 and p=0.04, respectively). A high relative abundance of Vδ2+ T cells was also associated with a lower incidence of EBV infection (p=0.02). Patients with EBV infection on the other hand showed higher absolute Vδ1+ T cell counts at days +100 and +180 after transplantation (p=0.046 and 0.038, respectively) than those without EBV infection. This result remained significant in a multivariate time-averaged analysis (q<0.1). Our results suggest a protective role of γδ T cells and especially Vδ2+ T cell subset against the development of aGvHD and EBV infection after pediatric HSCT. Vδ1+ T cells might be involved in the immune response after EBV infection. Our results encourage further research on γδ T cells as prognostic markers after HSCT and as possible targets of adoptive T cell transfer strategies. [ABSTRACT FROM AUTHOR]

This document summarizes a study on the risk of sinusoidal obstruction syndrome (SOS) in patients with acute lymphoblastic leukemia (ALL) who were treated with inotuzumab ozogamicin (InO). The study found that patients who underwent hematopoietic stem cell transplantation (HSCT) after InO therapy had the highest risk of developing SOS, particularly those with relapsed or refractory disease. The study also mentioned that changes in InO treatment protocols have helped decrease the occurrence of SOS. The document provides valuable information for researchers and healthcare professionals studying the use of InO in the treatment of B-cell ALL. [Extracted from the article]

Purpose: To assess the use of bone marrow aspirate (BM) and bone marrow aspirate concentrate (BMAC) in the treatment of long-bone nonunion and to understand mechanism of action. Methods: A systematic review of PubMed and EBSCOHost was completed to identify studies that investigated the use of BM or BMAC for the diagnosis of delayed union and/or nonunion of long-bone fractures. Studies of isolated bone marrow-mesenchymal stem cells (BM-MSCs) and use in non-long-bone fractures were excluded. Statistical analysis was confounded by heterogeneous fracture fixation methods, treatment history, and scaffold use. Results: Our initial search yielded 430 publications, which was screened down to 25 studies. Successful treatment in aseptic nonunion was reported at 79–100% (BM) and 50–100% (BMAC). Septic nonunion rates were slightly better at 73–100% (BM) and 83.3–100% (BMAC). 18/24 studies report union rates > 80%. One study reports successful treatment of septic nonunion with BMAC and no antibiotics. A separate study reported a significant reduction in autograft reinfection rate when combined with BMAC (P = 0.009). Major adverse events include two deep infections at injection site and one case of heterotopic ossification. Most studies note transient mild donor site discomfort and potential injection site discomfort attributed to needle size. Conclusion: The current literature pertaining to use of BM/BMAC for nonunion is extremely heterogeneous in terms of patient population and concomitant treatment modalities. While results are promising for use of BM/BMAC with other gold standard treatment methodologies, the literature requires additional Level I data to clarify the impact of role BM/BMAC in treating nonunion when used alone and in combination with other modalities. Level of evidence: Level III. [ABSTRACT FROM AUTHOR]