bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Awareness and Discussions of Incurability in Patients with Pretreated Non-Small Cell Lung Cancer and Caregivers: A Prospective Cohort Study
Authors: Hasegawa Takaaki , Okuyama Toru , Uemura Takehiro , Matsuda Yoshinobu , Otani Hiroyuki , Shimizu Junichi , Horio Yoshitsugu , Watanabe Naohiro , Yamaguchi Teppei , Fukuda Satoshi , Oguri Tetsuya , Maeno Ken , Tamiya Akihiro , Nosaki Kaname , Fukumitsu Kensuke , Akechi Tatsuo 
Published: September 2022

AbstractBackgroundAlthough patients with advanced cancer often have poor prognostic awareness, the most effective communication approach for improving prognostic awareness is unclear. In addition, the association between prognostic awareness and preferences for future medical treatment remains unexplored.Materials and MethodsWe performed a prospective observational study of consecutive patients with advanced or post-operative recurrent non-small cell lung cancer whose disease had progressed after first–line chemotherapy, and their caregivers. We evaluated patterns of clinical discussions about incurability, prognostic awareness, and preference for future medical treatment at baseline and 3 months later.ResultsWe obtained 200 valid responses to the questionnaires at baseline and 147 valid responses 3 months later. In addition, 180 caregivers returned valid responses. A total of 54% of patients and 51% of caregivers had accurate awareness at baseline, and 52% of patients had accurate awareness 3 months later. Multiple logistic regression analysis revealed that patients who were informed about incurability in recent and past discussions were significantly more likely to have accurate awareness 3 months later, compared with those who were only informed recently (adjusted odds ratio 5.08; 95% CI, 1.31-19.78; P = .019). Accurate awareness at 3 months was significantly negatively associated with preference for life-prolonging treatment at 3 months after adjusting for covariates (adjusted odds ratio 0.39; 95% CI, 0.17-0.90; P = .028).ConclusionPatients with advanced cancer who had both recent and past discussions about incurability with their oncologists have more accurate prognostic awareness. Improving prognostic awareness could reduce the preference for life-prolonging treatment.
Safety of Scrambler Therapy: A Systematic Review of Complications and Adverse Effects
Authors: Wang Eric J , Limerick Gerard , D’Souza Ryan S , Lobner Katie , Williams Kayode A , Cohen Steven P , Smith Thomas J 
Published: September 2022

AbstractObjectiveThe objective was to qualitatively synthesize all reported cases of complications, adverse effects, side effects, or harms arising from the use of scrambler therapy (ST).Methods and DesignA systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The PubMed, Embase, Scopus, Web of Science, United States National Library of Medicine clinical trials registry, and Cochrane Central Register of Controlled Trials databases were searched from database inception to December 10, 2021. Case reports/series, abstracts, retrospective studies, and prospective studies (e.g., open-label trials, randomized controlled trials) pertaining to ST and any description of a complication, adverse effect, side effect, or harm were screened. The search protocol was developed a priori and registered via the International Prospective Register of Systematic Reviews (PROSPERO ID: CRD42021291838).ResultsA total of six RCTs, 19 prospective open-label trials, and 11 case series / case reports met the inclusion criteria, comprising 1,152 total patients. Two patients experienced contact dermatitis, and one patient reported minor ecchymosis that resolved without intervention. This yielded a composite complication rate of 0.26% (3/1,152). There were zero reported serious adverse events.ConclusionsWhen used in accordance with the treatment protocols described by the United States Food and Drug Administration and device manual, ST is associated with a reported composite complication rate that is orders of magnitude lower than those of invasive neuromodulation devices. ST neuromodulation is a safe alternative for patients who cannot undergo invasive neuromodulation device implantation because of either risk or preference.
Differential pulse oximetry readings between ethnic groups and delayed transfer to intensive care units
Authors: Crooks C J , West J , Morling J R , Simmonds M , Juurlink I , Briggs S , Cruickshank S , Hammond-Pears S , Shaw D , Card T R , Fogarty A W 
Published: September 2022

SummaryBackgroundPulse oximeters are widely used to monitor blood oxygen saturations, although concerns exist that they are less accurate in individuals with pigmented skin.AimsThis study aimed to determine if patients with pigmented skin were more severely unwell at the period of transfer to intensive care units (ICUs) than individuals with White skin.MethodsUsing data from a large teaching hospital, measures of clinical severity at the time of transfer of patients with COVID-19 infection to ICUs were assessed, and how this varied by ethnic group.ResultsData were available on 748 adults. Median pulse oximetry demonstrated similar oxygen saturations at the time of transfer to ICUs (Kruskal–Wallis test, P = 0.51), although median oxygen saturation measurements from arterial blood gases at this time demonstrated lower oxygen saturations in patients classified as Indian/Pakistani ethnicity (91.6%) and Black/Mixed ethnicity (93.0%), compared to those classified as a White ethnicity (94.4%, Kruskal–Wallis test, P = 0.005). There were significant differences in mean respiratory rates in these patients (P &lt; 0.0001), ranging from 26 breaths/min in individuals with White ethnicity to 30 breaths/min for those classified as Indian/Pakistani ethnicity and 31 for those who were classified as Black/Mixed ethnicity.ConclusionsThese data are consistent with the hypothesis that differential measurement error for pulse oximeter readings negatively impact on the escalation of clinical care in individuals from other than White ethnic groups. This has implications for healthcare in Africa and South-East Asia and may contribute to differences in health outcomes across ethnic groups globally.
Sexual and Reproductive Health in Adolescents and Young Adults With Psychotic Disorders: A Scoping Review
Authors: Vickers Mark L , Choi Yoon Kwon , Eriksson Lars , Polyakova-Nelson Yekaterina , Jokovic Zorica , Parker Stephen D , Moudgil Vikas , Dean Judith A , Debattista Joseph , Scott James G 
Published: September 2022

Abstract

Background and Hypothesis
The sexual and reproductive health (SRH) of young people with psychosis has been largely overlooked. We hypothesised that there are key deficiencies in the existing literature on the SRH of adolescents and young adults with psychotic disorders.

Study Design
We conducted a systematic scoping review using Pubmed, Web of Science, Embase, PsycINFO, and CINAHL. We included empirical studies and case reports focused on SRH issues in young people (aged 14–24 years) with psychotic disorders. A qualitative synthesis was completed. Joanna Briggs Institute Critical Appraisal Tools were utilized to assess study quality.

Study Results
Seventeen empirical studies and 52 case reports met inclusion criteria. Most focused on sexual dysfunction which was identified as common among this cohort and associated with both psychotic disorders and antipsychotics. The study population was more likely to engage in sexual risk-taking behavior and was at higher risk of sexually transmissible infections than those without psychosis. SRH topics of clinical relevance in older patients with psychosis such as pregnancy, abortion, sexual violence, coercion, sexual identity, and gender were poorly addressed in this younger group. We found empirical studies generally lacked identification and controlling of confounders whilst case reports provided limited description of mental health and SRH outcomes following clinical intervention.

Conclusion
Research and clinical practice addressing sexual and reproductive health is needed for young people living with psychosis. To address research gaps future studies should focus on women’s health, sexual violence, gender, and sexuality in young people with psychosis.
Abstract 4 Umbilical Cord-Derived Mesenchymal Stromal Cells Suppress Neuroinflammation and Promote Remyelination in the Spinal Cord
Authors: Min Hyunjung , Xu Li , Parrott Roberta , Kurtzberg Joanne , Filiano Anthony 
Published: September 2022

Abstract

Introduction
Mesenchymal stromal cells (MSCs) are one of the most widely tested cell therapies due to their ability to suppress inflammation. Demyelinating diseases of the central nervous system (CNS) are commonly accompanied by neuroinflammation, including infiltrating proinflammatory leukocytes and activation of resident macrophages (microglia and border-associated macrophages in the meninges). The precise mechanism of how MSCs suppress neuroinflammation is unclear; however, we recently described a novel pathway where MSCs physically interact with macrophages to reprogram the immune response through the transfer of a cytoplasmic organelle called a processing body (p-body).

Objective
We set out to study how human umbilical cord tissue-derived MSCs interact with CNS microglia and border macrophages to protect in a mouse model of spinal cord demyelination.

Methods
We manufactured several MSC lines under GMP conditions and tested their ability to interact with CNS macrophages and promote remyelination in multiple preclinical assays. To determine if p-bodies are critical for these steps, we depleted p-bodies using CRISPR/Cas9 targeting to DDX6. To test for effects on acute demyelination, we injected lysophosphatidylcholine (LPC) into the spinal cord or added LPC to organotypic cerebellar slice cultures. To test direct effects on microglia activation, we treated primary microglia or a microglia cell line with lipopolysaccharide.

Results
We determined that MSC promoted remyelination in the spinal cord and that this was dependent on p-bodies. MSC directly contacted CNS macrophages and inhibited their activation. Using primary microglia and a microglia cell line, we determined that MSCs suppress the release of proinflammation cytokines, IL-6, and TNF.

Discussion
We determined that MSCs suppress microglial cell activation and enhance remyelination of the spinal cord. Our study offers insight into a novel mechanism about how MSCs can alter the immune response via transferring p-bodies and enhance remyelination in CNS. Furthermore, our results may lead to a quick and simple potency assay to establish the efficacy of MSCs for suppressing neuroinflammation.
Abstract 6 Projected Impact of Omidubicel on Racial and Ethnic Disparities in Allogeneic Hematopoietic Cell Transplant Access and Outcomes for Patients with Hematologic Malignancies in the U.S.
Authors: Gergis Usama , Khera Nandita , Edwards Marie Louise , Song Yan , Sun Rochelle , Simantov Ronit , Sivaraman Smitha , Manghani Rocio , Signorovitch James 
Published: September 2022

Abstract

Introduction
Patients with hematologic malignancies (HM) who are eligible for allogeneic hematopoietic cell transplant (allo-HCT) often lack an HLA-matched related donor (MRD) and rely on unrelated donors for a matched or mismatched unrelated donor (MUD or MMUD) or on umbilical cord blood (UCB). It is well known that racial minorities are underrepresented in donor registries.

Objective
Omidubicel, an advanced cell therapy for allo-HCT, demonstrated superior hematopoietic recovery and clinical outcomes compared with standard UCB (NCT02730299). We hypothesized the impact of omidubicel access on racial and ethnic health disparities in a projection model.

Methods
A model was developed to project allo-HCT access and clinical outcomes in a hypothetical population of 10,000 allo-HCT-eligible US patients with HM lacking an HLA-MRD. Outcomes associated with omidubicel, MUD, MMUD, haploidentical or UCB HCT, or no transplant were assessed by race/ethnic group. Model inputs, including clinical outcomes for each HCT type, were drawn from clinical trials, public CIBMTR and US Department of Health and Human Services data, and published studies. Increasing omidubicel use was modeled, with proportional reductions in other allo-HCT types or no transplant.

Results
In a modeled population of 10,000 patients, 5,956 (60%) received allo-HCT utilizing current donor sources (MUD, MMUD, haploidentical, UCB) with no omidubicel (status quo). While 80% of white patients underwent allo-HCT, only 40% of Hispanic, 32% of Asian, and 22% of Black patients underwent allo-HCT. Mean time from selecting graft to HCT was 11.5 weeks. Including those not transplanted, 1-year OS was 62% overall, ranging from 56% (Black) to 65% (White). Modeled increases in omidubicel use in eligible patients were associated with higher proportions of patients undergoing allo-HCT, decreased time to HCT, and increased 1-year OS. Improvements were greatest among racial minorities. Assuming 20% omidubicel use, the proportion of patients receiving allo-HCT increased by 71% in Black, 43% in Asian, 30% in Hispanic, and 5% in White patients. Modeled time to allo-HCT improved as well.

Discussion
Access to omidubicel is projected to decrease time to allo-HCT, improve outcomes overall, with greatest improvements among racial and ethnic groups underserved by the status quo, thus helping to reduce racial disparities and improving health equity in allo-HCT.
Abstract 7 Reduced Intensity Conditioning Umbilical Cord Blood Transplantation in Combination with Splenic Irradiation in a Patient with Secondary Myelofibrosis and Massive Splenomegaly
Authors: Kaabneh Basil , Torres Nancy , Maguire Craig , Aljitawi Omar 
Published: September 2022

Abstract

Introduction
Myelofibrosis (MF) is a bone marrow neoplasm characterized by marrow fibrosis/failure and splenomegaly, causing pain, early satiety, and cytopenia. The only curative option is allogeneic hematopoietic stem cell transplant (allo-HSCT); however, its use is limited due to donor availability and patient age, functional status, and comorbidities. Umbilical cord blood (UCB) has been explored in this population for this reason with variable success, partly related to splenomegaly, which might influence engraftment in MF patients.

Objective
The objective was to report the successful use of UCB transplantation in conjunction with splenic irradiation to treat a patient with advanced MF and massive splenomegaly.

Methods
A 71-year-old male with post-essential thrombocythemia MF was treated with ruxolitinib for 2 years but developed worsening cytopenia and transfusion dependence. Splenomegaly (19.1×7.1×20.8 cm) was identified. Allo-HSCT was recommended on the basis of high-risk disease (DIPSS Plus score: 4) and few alternative options. Although suitable HLA-matched donors were unattainable, two cord blood units were available. A reduced intensity conditioning regimen of fludarabine, cyclophosphamide, and TBI 300 was chosen. Given the primary resistance to ruxolitinib, the spleen was irradiated with 450 cGy prior to transplant.

Results
Neutrophil and platelet engraftment occurred on days +30 and +49, respectively. The patient developed engraftment syndrome and acute graft versus host disease (GVHD) that resolved with methylprednisolone and early introduction of ruxolitinib. His immunosuppressive medications were discontinued by 6-months without evidence of chronic GVHD thereafter. He is now 1 year post-transplant with 100% donor chimerism and no clinical evidence of MF or GVHD.

Discussion
We present a novel therapeutic approach combining the use of splenic irradiation and a double unit UCB HSCT in a patient with MF and massive splenomegaly. UCB transplant should be considered in patients with MF who do not have an HLA-matched donor with the additional benefit of less chronic GvHD. Massive splenomegaly can negatively impact transplant outcomes due to entrapment of donor stem cells, delayed engraftment, and prolonged cytopenia. Splenic irradiation before UCB transplant can potentially reduce these complications, as it did in this case, and in turn decrease transplant-related mortality. Our future aim is to develop a clinical trial to study this approach.
Abstract 8 Health-Related Quality of Life (HRQL) Following Transplantation with Omidubicel Versus Umbilical Cord Blood (UCB) in Patients with Hematologic Malignancies: Results from a Phase III Randomized, Multicenter Study
Authors: Lin Chenyu , Sajeev Gautam , Sung Anthony , Stiff Patrick , Brunstein Claudio , Cutler Corey , Sanz Guillermo , Lindemans Caroline , Rezvani Andrew , Hanna Rabi , Koh Liang , Maziarz Richard , Hwang William , Song Yan , Liu Qing , Manghani Rocio , Sivaraman Smitha , Signorovitch James , Horwitz Mitchell 
Published: September 2022

Abstract

Introduction
Omidubicel, an advanced cell therapy used for allogeneic hematopoietic stem cell transplant has demonstrated faster hematopoietic recovery, shorter hospitalization, and lower rates of bacterial, viral, and invasive fungal infections compared with umbilical cord blood (UCB) in a phase III randomized trial (NCT02730299;Blood 2021;138:1429).

Objective
The objective was to compare changes in health-related quality of life (HRQL) between treatment groups in the phase III trial.

Methods
Patients who received protocol-defined treatment and provided HRQL evaluations at baseline and ≥1 follow-up visit were analyzed. Outcomes included Functional Assessment of Cancer Therapy General (FACT-G) domain scores for physical, social/family, functional and emotional well-being, and EQ-5D-3L index scores, at days 42, 100, 180, and 365 post-transplant. HRQL changes from baseline were compared using mixed effect models with repeated measures, adjusting for age, sex, race, region, primary diagnosis, HCT comorbidity index, and baseline HRQL score. Average HRQL over time was compared using the area under the curve (AUC) of mean HRQL trajectories in each treatment group.

Results
Seventy-five patients (omidubiceln = 37, UCB n = 38) provided HRQL data for inclusion and were representative of the full randomized population (N = 125) at baseline. Median age was 38 years, and 41% were female. During the first year post-transplant, patients receiving omidubicel had numerically superior average FACT-G domain and EQ-5D-3L index scores compared with UCB, with mean differences across time points ranging from 1.4 to 3.1 for physical well-being, 0 to 1.3 for social/family well-being, 0.5 to 1.4 for emotional well-being, 1.6 to 3.2 for functional well-being, and 0.03 to 0.09 for the EQ-5D-3L index score. Minimal clinically important differences (MCIDs) were exceeded at ≥1 time point for mean physical and functional well-being (MCIDs = 2 units) and for the EQ-5D-3L (MCID = 0.07 units). Initial mean declines in HRQL occurred for all measures at day 42 and were consistently numerically smaller in the omidubicel group than in the UCB group. Averaging across the first year post-transplant, patients receiving omidubicel had significantly improved HRQL for physical and functional well-being domains (P &lt; .05 for comparison of AUCs).

Discussion
Along with faster time to engraftment, lower infection risk, and shorter hospitalization, omidubicel was associated with meaningfully greater preservation or improvement of important HRQL domains compared with UCB.
Abstract 9 Hematopoietic Stem Cell Transplantation (HSCT) with Omidubicel Leads to Robust Recovery and Diversity of T Cells
Authors: Szabolcs Paul , Yackoubov Dima , Levy Stuart , Chen Xiaohua , Horwitz Mitchell 
Published: September 2022

Abstract

Introduction
Omidubicel is a cell therapy used for allogeneic hematopoietic stem cell transplant. A phase III randomized study (NCT02730299) comparing omidubicel to umbilical cord blood (UCB) demonstrated faster hematopoietic recovery, lower rates of infection, shorter hospitalization time (Horwitz et al.Blood. 2021;138[16]:1429-1440) and robust immune reconstitution (Szaboles et al. Trans Cell Ther. 2022;28[suppl]:S5).

Objective
We now characterize T-cell development reflected by T-cell receptor excision circles (TREC) and T-cell receptor (TCR) diversity in omidubicel and UCB-transplanted patients (pts).

Methods
Genomic DNA was extracted from peripheral blood mononuclear cells. TREC was quantified by real-time quantitative PCR. TREC copies (T) were standardized to β actin transcripts (B), and T/B ratio was normalized per µg of DNA. TCR diversity was measured using a total of 76 T-cell receptor β locus (TRB) genes. Human T-cell receptor β repertoire was quantified using AmpliSeq for Illumina Immune Repertoire Plus SR assay. TCRβ metrics quantified the number of clones, Shannon’s entropy, clonality, evenness, convergency, and Gini indexes.

Results
A total of 37 pts from 15 sites were included, 17 transplanted with omidubicel and 20 with UCB. Median CD3+ cell dose was lower for pts transplanted with omidubicel (1.8 × 106 cells/kg; range: 1.2-7.6) than with UCB (6.0 × 106 cells/kg, range: 1.7-10.2). Patients transplanted with omidubicel and UCB had similar TREC and recent thymic emigrants (RTE) counts in peripheral blood at days 100 and 180. At day 365, RTEs were higher in omidubicel (113 ± 85 cells/µL) than UCB (41 ± 15 cells/µL, P = .047). Median T/B ratio was 223 for omidubicel and 124 for UCB. There was no significant difference in TCR repertoire diversity between the omidubicel and UCB groups.

Discussion
Pts transplanted with omidubicel had robust and diverse T-cell reconstitution. Higher numbers of de-novo thymus educated T-cells in peripheral blood at 1 year suggest faster thymopoiesis in patients transplanted with omidubicel than with UCB. These data are further evidence for the robust immune reconstitution in patients treated with omidubicel and provide mechanistic rationale for the lower infection rates and improved outcomes in these patients.