UNASSIGNED: Variation in the provision of care and outcomes in the last months of life by cancer and non-cancer conditions is poorly understood.
UNASSIGNED: (1) To describe patient conditions, symptom burden, practical problems, service use and dissatisfaction with end-of-life care for older adults based on the cause of death. (2) To explore factors related to these variables focussing on the causes of death.
UNASSIGNED: Secondary analysis of pooled data using cross-sectional mortality follow-back surveys from three studies: QUALYCARE; OPTCare Elderly; and International Access, Right, and Empowerment 1.
UNASSIGNED: Data reported by bereaved relatives of people aged ⩾75 years who died of cancer, cardiovascular disease, respiratory disease, dementia or neurological disease.
UNASSIGNED: The pooled dataset contained 885 responses. Overall, service use and circumstances surrounding death differed significantly across causes of death. Bereaved relatives reported symptom severity from moderate to overwhelming in over 30% of cases for all causes of death. Across all causes of death, 28%-38% of bereaved relatives reported some level of dissatisfaction with care. Patients with cardiovascular disease and dementia experienced lower symptom burden and dissatisfaction than those with cancer. The absence of a reliable key health professional was consistently associated with higher symptom burden (p = 0.002), practical problems (p = 0.001) and dissatisfaction with care (p = 0.001).
UNASSIGNED: We showed different trajectories towards death depending on cause. Improving symptom burden and satisfaction in patients at the end-of-life is challenging, and the presence of a reliable key health professional may be helpful.

Bone marrow transplantation for non-malignant diseases such as aplastic anemia and hemoglobinopathies is a burgeoning clinical area. The goal of these transplants is to correct the hematopoietic defect with as little toxicity as possible. This requires mitigation of transplant-specific toxicities such as graft versus host disease, given this is not needed in non-malignant disorders. This review details current clinical outcomes in the field with a focus on post-transplantation cyclophosphamide and anti-thymoglobulin as intensive graft versus host disease prophylaxis to achieve that goal.

MicroRNAs are a set of small non-coding RNAs that could change gene expression with post-transcriptional regulation. MiRNAs have a significant role in regulating molecular signaling pathways and innate and adaptive immune system activity. Moreover, miRNAs can be utilized as a powerful instrument for tissue engineers and regenerative medicine by altering the expression of genes and growth factors. MiR-1290, which was first discovered in human embryonic stem cells, is one of those miRNAs that play an essential role in developing the fetal nervous system. This review aims to discuss current findings on miR-1290 in different human pathologies and determine whether manipulation of miR-1290 could be considered a possible therapeutic strategy to treat different non-malignant diseases. The results of these studies suggest that the regulation of miR-1290 may be helpful in the treatment of some bacterial (leprosy) and viral infections (HIV, influenza A, and Borna disease virus). Also, adjusting the expression of miR-1290 in non-infectious diseases such as celiac disease, necrotizing enterocolitis, polycystic ovary syndrome, pulmonary fibrosis, ankylosing spondylitis, muscle atrophy, sarcopenia, and ischemic heart disease can help to treat these diseases better. In addition to acting as a biomarker for the diagnosis of non-malignant diseases (such as NAFLD, fetal growth, preeclampsia, down syndrome, chronic rhinosinusitis, and oral lichen planus), the miR-1290 can also be used as a valuable instrument in tissue engineering and reconstructive medicine. Consequently, it is suggested that the regulation of miR-1290 could be considered a possible therapeutic target in the treatment of non-malignant diseases in the future.

Haploidentical hematopoietic cell transplantation (HCT) is a valuable curative option for children with non-malignant diseases. Haploidentical HCT using post-transplant cyclophosphamide (PTCy) is a readily available option in the absence of an HLA-matched donor. We conducted a retrospective single-center study on the outcome of haploidentical HCT in children with non-malignant diseases. We gathered data from 44 patients underwent HCT in the period 2015 to 2020. The indications for HCT were bone marrow failure, primary immunodeficiency, metabolic disorders, and hemoglobinopathy. Median age at HCT was 4 years (range 0.7-20). The conditioning regimens were myeloablative (n = 17) or reduced intensity (n = 27). After a median follow-up of 20 months (range 4-71), 2-year overall survival was 89% and 2-year GvHD-free relapse-free survival (GRFS) was 66%. Incidence of primary graft failure was 13.6%. Cumulative incidence of grade II-IV acute and moderate/severe chronic GvHD were 20% and 6.4%, respectively. Younger age at HCT (< 4 years) and primary immunodeficiency were significantly associated with better GRFS (p < 0.05). In conclusion, haploidentical HCT using PTCy is feasible and curative in children with non-malignant diseases lacking an HLA-matched donor. Early diagnosis and referral in addition to timely treatment can further improve outcomes.

The overall objective of allogeneic hematopoietic cell transplantation (HCT) in patients with non-malignant conditions involves replacing a dysfunctional or absent cell or gene product for disease correction. It is unclear whether lower busulfan exposure may be sufficient in this population to facilitate durable myeloid engraftment and limit toxicity. Given that neither the ideal level of mixed myeloid chimerism for specific non-malignant diseases nor how to condition a patient to achieve stable mixed myeloid chimerism is fully known, we sought to analyze the relationships among busulfan exposure, myeloid chimerism, and outcomes in patients with non-malignant conditions receiving busulfan as a part of combination pretransplant conditioning at our institution. This was a single-center, retrospective study including pediatric patients with a variety of non-malignant disorders who underwent allogeneic HCT at the University of California San Francisco Benioff Children\'s Hospital from March 2007 to June 2018. The busulfan cumulative area under the curve (cAUC) was estimated using a validated population pharmacokinetic model and nonlinear mixed effects modeling. Median busulfan cAUC for all patients was 70 mg·h/L (range, 53 to 108). All of the 29 patients with a busulfan cAUC of ≥70 mg·h/L achieved long-term disease correction with full or stable mixed (>20%) myeloid chimerism, compared to 78.5% (22/28) of patients with a cAUC of <70 mg·h/L (P = .01). Overall ksurvival was evaluated up to 3 years and was identical in patients with busulfan cAUC < 70 mg·h/L and patients with busulfan cAUC ≥70 mg·h/L (96% versus 93%; P = .92). Only three patients died, at days 65, 164 and 980 days post-HCT. Severe busulfan-related toxicities and graft-versus-host-disease (GVHD) were rare, with veno-occlusive disease occurring in four patients (7%), acute respiratory distress syndrome in three patients (5%), and GVHD in five patients (9%). These results demonstrate excellent outcomes and extremely low rates of toxicity across our entire cohort. Based on the results of this study, we recommend a busulfan exposure target of 75 mg·h/L (range, 70 to 80) in all non-malignant patients receiving allogeneic HCT to ensure optimal exposure for achievement of high-level stable myeloid chimerism.

BACKGROUND: Unmanipulated haploid HSCT for SAA has resulted in improved outcomes over recent years. However, studies related to unmanipulated haploid HSCs combined with tp-UCB transplantation for other types of NMD are rare. Accordingly, we present the outcomes of 109 pediatric patients with life-threatening NMD undergoing unmanipulated haploid HSCs combined with tp-UCB transplantation.
METHODS: We retrospectively investigated 109 pediatric patients with life-threatening NMD treated with unmanipulated haploid HSCs combined with tp-UCB transplantation in a single center.
RESULTS: The median days of neutrophil and platelet engraftment were +13 and +22 days, respectively. None of the cases experienced PGF. The incidence rates for grade I-II, III-IV aGVHD and cGVHD were 44.9%, 24.8%, and 9.3%, respectively. The incidence rates of CMV and EBV viremia were 46.7% and 39.4%, respectively. The median follow-up duration was 997 days. In total, 106 patients survived, including 104 cases with FFS and 2 cases with SGF. Three patients died. The 5-year TRM, OS, and FFS were 2.8%, 97.2%, and 96.2%, respectively.
CONCLUSIONS: The results of unmanipulated haploid HSCs combined with tp-UCB in pediatric patients with life-threatening NMD were promising. However, further research is now needed to determine specific factors that might influence the engraftment of HSCs.

OBJECTIVE: Describe the GETH haploidentical stem cell transplantation (haplo-HSCT) activity in non-malignant disease (NMDs).
METHODS: We retrospectively analyzed data from children with NMDs who underwent haplo-HSCT.
RESULTS: From January 2001 to December 2016, 26 pediatric patients underwent 31 haplo-HSCT through ex vivo T cell-depleted (TCD) graft platforms or post-transplantation cyclophosphamide (PT-Cy) at 7 Spanish centers. Five cases employed unmanipulated PT-Cy haplo-HSCT, 16 employed highly purified CD34+ cells, and 10 employed ex vivo TCD grafts manipulated either with CD3+ CD19+ depletion, TCRαβ+ CD19+ selection or naive CD45RA+ T-cell depletion. Peripheral blood stem cells were the sole source for patients following TCD haplo-HSCT, and bone marrow was the source for one PT-Cy haplo-HSCT. The most common indications for transplantation were primary immunodeficiency disorders (PIDs), severe aplastic anemia, osteopetrosis, and thalassemia. The 1-year cumulative incidence of graft failure was 27.4%. The 1-year III-IV acute graft-versus-host disease (GvHD) and 1-year chronic GvHD rates were 34.6% and 16.7%, respectively. The 2-year overall survival was 44.9% for PIDs, and the 2-year graft-versus-host disease-free and relapse-free survival rate was 37.6% for the other NMDs. The transplantation-related mortality at day 100 was 30.8%.
CONCLUSIONS: Although these results are discouraging, improvements will come if procedures are centralized in centers of expertise.

Hematopoietic stem cell transplantation (HCT) is a curative intervention in non-malignant disorders (NMD) that benefit from donor-derived hematopoiesis, immunity, and establishment of vital cells or enzyme systems. Stability or reversal of disease symptoms depends on adequacy and long-term stability of donor cell engraftment in the compartment of interest. Unlike hematologic malignancies where complete replacement with donor derived hematopoiesis is desirable for a cure, NMD manifestations can often be controlled in the presence of mixed chimerism. This allows for exploration of reduced intensity conditioning regimens that can limit organ toxicity, late effects, and increase tolerability especially in young recipients or those with a large burden of disease related morbidity. However, the levels of donor chimerism conducive to disease control vary between NMD, need to focus on the hematopoietic lineage necessary to correct individual disorders, and need to be assessed for stability over time, i.e., a whole lifespan. An enhanced ability to reject grafts due to recipient immune competence, alloimmunization, and autoimmunity add to the complexity of this balance making NMD a highly diverse group of unrelated disorders. The addition of donor factors such as stem cell source and Human-Leukocyte-Antigen match extend the complexity such that \'one size does not fit all\'. In this perspective, we will discuss current knowledge of the role of chimerism and goals, approach to HCT, and emerging methods of boosting engraftment and graft function, and monitoring recommendations. We draw attention to knowledge gaps and areas of necessity for further research and research support.

In view of the roles of long non-coding RNA CDKN2B antisense RNA 1 (CDKN2BAS1) in various human diseases, we investigated the function of CDKN2B-AS1 and explored its therapeutic and prognostic target value in multiple biological processes. The aim of this review was to explore the molecular mechanism and clinical significance of CDKN2B-AS1 in various types of diseases.
In this review, the biological functions and mechanisms of lncRNA CDKN2B-AS1 in a variety of pathophysiological processes were summarized and analyzed. The correlated studies were collected via a systematic search of PubMed, Wiley Online Library, and ScienceDirect.
CDKN2B-AS1 is a potential long non-coding RNA that has been shown to be aberrantly expressed in various malignancies, containing hepatocellular carcinoma, intrahepatic cholangiocarcinoma, esophageal squamous cell carcinoma, gastric cancer, colonic adenocarcinoma, cervical cancer, ovarian cancer, breast cancer, glioma, lung cancer, laryngeal squamous cell carcinoma and osteosarcoma, involving in the processes of tumor cells proliferation, migration, invasion and inhibition of tumor cells apoptosis. Besides, CDKN2B-AS1 has been proved implicated in numerous non-malignant diseases, such as idiopathic pulmonary fibrosis, endometriosis, inflammatory bowel disease, intracranial aneurysm, diabetes mellitus and its complications, primary open angle glaucoma, ischemic stroke, atherosclerosis, coronary artery diseases, hypertension and heart failure, participating in the procession of lipid, carbohydrate metabolism and inflammation regulation.
Long non-coding RNA CDKN2B-AS1 likely serves as a promising therapeutic target or prognosis biomarker in multiple human diseases.

This multicenter retrospective study included 184 children with malignant and non-malignant diseases who underwent UCBT between January 1998 and August 2012. The malignant disease group included 101 children with ALL, AML, CML, JMML, and MDS, and the non-malignant disease group included 83 children with PID, β-thalassemia, IMD BMF, and HLH. The median duration to neutrophil and platelet engraftment was 16 and 35 days in the malignant disease group vs 15 and 38 days in the non-malignant disease group. The cumulative incidence of grade II-IV aGVHD and cGVHD was 25.6% and 13.5% in the malignant disease group vs 19.7% and 11.1% in the non-malignant disease group, respectively. The median duration and cumulative incidence of neutrophil and platelet engraftment, and the cumulative incidence of grade II-IV aGVHD and cGVHD were similar between the two groups. Of the 184 pediatric patients, 114 patients survived during a median follow-up period of 14 months (range 4-138). The 5-year OS and DFS were not statistically different between the two groups (56.3% and 46.1% in malignant disease group vs 68.5% and 52.8% in non-malignant disease group). The above results indicate that UCB is a viable source for HSCT for children with malignant or non-malignant diseases, especially in urgent cases.