bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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

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

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

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 < .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

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.
Abstract 10 Interim Results of a Phase I Study Investigating a Cord Blood-Derived Natural Killer Cell Therapy for Patients Hospitalized with COVID-19
Authors: Tercero Almudena , Finlay Dan , Asghedom Liya H , Romasanta Gladys R , Rice Natalie T , Ranjbaran Fatima , Stoltzman Carrie , Cook Jody , Blake Joe , Delaney Colleen , Hill Joshua A
Published: September 2022

Introduction

In the setting of viral infections, including infection with SARS-CoV-2, lymphocyte exhaustion and lymphopenia are common. Patients with COVID-19 who develop lymphopenia, particularly low numbers of circulating natural killer (NK) cells, are at high risk for disease progression. Thus, strategies that overcome profound lymphopenia and restore innate immune function may reduce the severity of COVID-19. One approach is the direct infusion of an exogenous source of healthy, functional NK cells intended to boost the patient’s immune system during the viral infection, enabling elimination of infected cells. “DVX201” is a cord blood-derived allogeneic NK cell therapy that is cryopreserved and intended for “off-the-shelf use” without HLA-matching.

Objective

The primary objective of this study is to investigate the safety and to identify the recommended phase II dose and/or the maximum tolerated dose (MTD) of DVX201 in patients hospitalized with COVID-19.

Methods

We are conducting an open-label, nonrandomized phase I safety and dose-finding (modified 3+3) study of DVX201 at three dose levels in patients hospitalized with COVID-19. Adult patients with documented SARS-CoV-2 infection were eligible if they were admitted to the hospital, were receiving ≤6 L supplemental oxygen by low flow delivery, and did not have other evidence of cytokine storm based on levels of serum IL-6, C-reactive protein, and ferritin.

Results

To date, 9 patients have been enrolled: 3 subjects at each dose level. All dose levels have been well tolerated, with no dose-limiting toxicities, infusion toxicities, or cytokine release syndrome observed. All patients were discharged from the hospital at an average of 5 days post infusion. Blood samples were drawn for correlative studies including persistence of DVX201, pre- and post-infusion immune system characterization, and cytokine panels. Accrual is continuing at the MTD.

Discussion

This trial will serve as the proof of concept for the use of DVX201 as an anti-viral treatment for COVID-19. These results will inform the potential role of DVX201 for treatment of other life-threatening viral infections by harnessing NK cells’ innate function to kill virally infected cells, regardless of the etiology of the infection.
Abstract 18 Developing a Potency Assay for Cord Tissue MSCs
Authors: Parrott Roberta , Noldner Pamela , Xu Li , Filiano Anthony , Shaz Beth , Kurtzberg Joanne
Published: September 2022

Introduction

The potency of mesenchymal stromal cells (MSCs) can be assessed by their ability to suppress proliferation of third party stimulated peripheral blood T cells. This correlates with decreased cellular production of IL-2Ra.

Objective

We optimized a potency assay for human cord tissue MSCs (hCT-MSC) in clinical trials for subjects with neuroinflammation. Originally, this T cell suppression assay required radioactive tritiated thymidine, rendering the assay difficult to use in a quality control laboratory for product release. Accordingly, we are developing a modified assay that eliminates the tritiated thymidine and instead tests for production of IL-2Rα in harvested supernatants.

Methods

The modified assay utilizes freshly thawed hCT-MSCs plated in a 96-well Corning CellBIND plate in Fuji Prime-XV XSFM MSC expansion medium at three concentrations. The hCT-MSCs are incubated 1-6 days at 37°C with humidified 5% CO2 until 80%-100% confluent. At this point, three different, previously qualified, normal control peripheral blood mononuclear cells (PBMCs) are suspended in RPMI 1640 with HEPES medium and 10% fetal bovine serum (FBS) with and without Dynabead (Human T-Activator CD3/CD28). After 4 additional days in culture, 75 µL of supernatant is removed and frozen at –80°C for future assaying of IL-10, TNFα, IFNg, and IL-2Ra using the Ella (Bio-Techne). IL-2Ra was determined to have the best correlation with the original method of suppression of proliferation. In the original radioactivity method after 4 days, the cells were pulsed with tritiated thymidine, harvested 6-10 hours after pulsing, and counted in the MicroBeta2 counter.

Results

Seventeen hCT-MSC lines were then tested in both assays. The passing criteria was >70% suppression in the radioactivity assays or >70% decrease in IL-2Ra production in the Ella assay. All 17 hCT-MSC lots passed in the radioactivity-based assay, while 16/17 lines passed using the IL-2Rα assay. Subsequently, the number of PBMCs plated per well and the number of days the PBMCs were in culture were optimized to maximize production of IL-2Rα.

Discussion

We developed a potency assay for MSCs that eliminates the use of radioactive reagents and usable as a release assay in manufacturing of hCT-MSC.
Abstract 31 Testing of Cord Blood Units for Non-Hematopoietic Markers
Authors: Frenet Emeline Masson , Watanabe Chiseko , Bentsen Helen , Chowtee Bryana , Liu WenJun , Romeo Cynthia , Sung Dorothy , Jimenez Alexandra
Published: September 2022

Introduction

Cord blood units (CBU) are tested at banking for markers relevant to donor safety (infectious disease markers) and hematopoietic stem cell transplantation (cellularity and HLA typing). As CBUs are being increasingly used for new, non-transplant purposes, additional markers are sometimes needed for CBU selection.

Objective

We describe here our procedure for testing CBU, looking for specific NK cell characteristics: KIR haplotype B (associated with more activating KIRs), and Fc gamma receptor III A (FCGR3A) 158 V/V (presence of a homozygous valine in position 158) polymorphism (which has a higher affinity for IgG), as requested by some of our clients for non-transplant studies.

Methods

First, a list of eligible CBUs was established, based on the order specifications. Testing was requested from an outside lab (Histogenetics, Ossining, New York). As CBU DNA is a precious resource, we wanted to limit the number of new samples to be sent by first testing leftover samples from HLA typing, then sending additional samples to the lab, to reach the required number of CBUs. Testing was done sequentially (Figure 1): first, KIR typing, then FCGR3A polymorphism on the CBU with KIR B haplotype.

Results

A total of 216 samples were selected for KIR testing (130 from stored DNA and 86 from newly sent DNA); 154 (71%) were found to have at least one B haplotype receptor. For those, FCGR3A polymorphism was tested; 60 samples (39%) were F/F, 70 (46%) F/V, and 23 (15%) V/V (Figure 1), in line with expected frequencies from the literature. Average TAT for KIR testing was 13 days and an additional 18 days for FCGRA3.

Discussion

Performing additional testing can easily be integrated into a bank’s routine and help select CBU for purposes other than transplantation. When several markers are needed, sequential testing is an efficient and cost-saving method.
A transition to online teaching and learning of mathematics in Norwegian higher education institutions: the perspectives of lecturers and students
Authors: Radmehr Farzad , Goodchild Simon
Published: September 2022

This paper reports a study of university lecturers’ and students’ experiences of teaching and learning mathematics following the abrupt requirement to switch to online teaching in 2020. A goal of the study is to share experiences that could be useful to improve the teaching and learning of mathematics in online settings. The qualitative research described is a phenomenological study and draws on interviews with ten mathematics lecturers and six undergraduate students who were enrolled in at least one university mathematical course during the lockdown in 2020. The interview data were analysed using a thematic approach. This paper reports findings regarding perceptions of lecturers and students about the challenges and benefits of online teaching and learning of mathematics, how the transition to online education has influenced assessment and sharing useful approaches for teaching and learning mathematics in online settings.
LncRNA HOTAIRM1 Involved in Nano NiO-Induced Pulmonary Fibrosis via Regulating PRKCB DNA Methylation-Mediated JNK/c-Jun Pathway
Authors: Zheng Jinfa , Wang Jinyu , Qin Xin , Li Kun , Gao Qing , Yang Mengmeng , Liu Han , Li Sheng , Chang Xuhong , Sun Yingbiao
Published: September 2022

Nickel oxide nanoparticles (Nano NiO) lead to pulmonary fibrosis, and the mechanisms are associated with epigenetics. This study aimed to clarify the regulatory relationship among long noncoding RNA HOXA transcript antisense RNA myeloid-specific 1 (HOTAIRM1), DNA methylation and expression of protein kinase C beta (PRKCB), and JNK/c-Jun pathway in Nano NiO-induced pulmonary fibrosis. Therefore, we constructed the rat pulmonary fibrosis model by intratracheal instillation of Nano NiO twice a week for 9 weeks and established the collagen deposition model by treating BEAS-2B cells with Nano NiO for 24 h. Here, the DNA methylation pattern was analyzed by whole-genome bisulfite sequencing in rat fibrotic lung tissues. Then, we integrated mRNA transcriptome data and found 93 DNA methylation genes with transcriptional significance. Meanwhile, the data showed that Nano NiO caused the down-regulation of lncRNA HOTAIRM1, the hypomethylation, and up-regulation of PRKCB2, JNK/c-Jun pathway activation, and collagen deposition (the up-regulated Col-I and α-SMA) both in vivo and in vitro. DNMTs inhibitor 5-AZDC attenuated Nano NiO-induced PRKCB2 expression, JNK/c-Jun pathway activation, and collagen deposition, but overexpression of PRKCB2 aggravated the changes mentioned indicators in Nano NiO-induced BEAS-2B cells. Furthermore, JNK/c-Jun pathway inhibitor (SP600125) alleviated Nano NiO-induced excessive collagen formation. Additionally, overexpression of HOTAIRM1 restrained the PRKCB hypomethylation, the activation of JNK/c-Jun pathway, and collagen formation induced by Nano NiO in BEAS-2B cells. In conclusion, these findings demonstrated that HOTAIRM1 could arrest Nano NiO-induced pulmonary fibrosis by suppressing the PRKCB DNA methylation-mediated JNK/c-Jun pathway.
Importation and circulation of rubella virus lineages 1E-L2 and 2B-L2c between 2018 and 2021 in China: Virus evolution and spatial–temporal transmission characteristics
Authors: Liu Ying , Han Zhenzhi , Kang Chuyun , Cui Aili , Zhang Yan , Liu Li , Chen Ying , Deng Lili , Zhao Hua , Zhou Jun , Li Fangcai , Zhou Shujie , Feng Daxing , Tian Xiaoling , Feng Yan , Cui Xiaoxian , Lei Yue , Wang Yan , Yuan Fang , Fan Lixia , Tang Xiaomin , Chen Meng , Peng Xiaofang , Guo Yu , Gao Hui , Wang Suting , Li Liqun , Zhang Ting , Deng Xiuying , Chen Haiyun , Wang Shuang , Ma Yu , Zhu Zhen , Xu Wenbo
Published: September 2022

To better understand the importation and circulation patterns of rubella virus lineages 1E-L2 and 2B-L2c circulating in China since 2018, 3,312 viral strains collected from 27 out of 31 provinces in China between 2018 and 2021 were sequenced and analyzed with the representative international strains of lineages 1E-L2 and 2B-L2c based on genotyping region. Time-scale phylogenetic analysis revealed that the global lineages 1E-L2 and 2B-L2c presented distinct evolutionary patterns. Lineage 1E-L2 circulated in relatively limited geographical areas (mainly Asia) and showed geographical and temporal clustering, while lineage 2B-L2c strains circulated widely throughout the world and exhibited a complicated topology with several independently evolved branches. Furthermore, both lineages showed extensive international transmission activities, and phylogeographic inference provided evidence that lineage 1E-L2 strains circulating in China possibly originated from Japan, while the source of lineage 2B-L2c isolated since 2018 is still unclear. After importation into China in 2018, the spread of lineage 1E-L2 presented a three-stage transmission pattern from southern to northern China, whereas lineage 2B-L2c spread from a single point in western China to all the other four regions. These two transmission patterns allowed both imported lineages to spread rapidly across China during the 2018–9 rubella epidemic and eventually established endemic circulations. This study provides critical scientific data for rubella control and elimination in China and worldwide.
COVID-19 Vaccines for Children with Developmental Disabilities: Survey of New York State Parents' Willingness and Concerns
Authors: Bonuck Karen , Iadarola Suzannah , Gao Qi , Siegel Joanne F.
Published: September 2022

Objective:

While 1 in 6 US children have a developmental disability (DD), and such children are disproportionately affected by COVID-19, little is known about their vaccination status. We surveyed New York State parents of children with DDs to ascertain willingness and concerns regarding COVID-19 vaccines.

Methods:

An online survey was distributed to statewide DD networks from June to September 2021 (vaccines were authorized for adolescents in May 2021). We report associations between vaccine willingness and concerns and race/ethnicity, child age, in-person schooling, routine/flu vaccinations, and DD diagnoses. Willingness was categorized as “got/will get ASAP” (high), “wait and see/only if required,” or “definitely not.”

Results:

A total of 352 parents (49.1% White) responded. Willingness differed by age (p < 0.001). High willingness was reported for 73.9%, 50.0%, and 36.0% of children aged 12 to 17, 6 to 11, and 0 to 5 years, respectively. Willingness differed by autism diagnosis (p < 0.01) and routine and flu vaccination status (p < 0.001). Predominant concerns included side effects (89%) and children with disabilities not being in trials (80%). Less common concerns were COVID not serious enough in children to warrant vaccine (23%) and misinformation (e.g., microchips, 5G, DNA changes) (24%). Concerns about vaccine safety differed by age (p < 0.01) and were highest for older and then the youngest children. In age-stratified adjusted models, attention-deficit/hyperactivity disorder was negatively associated with high willingness for age 5 or younger (OR = 0.02, 95% confidence interval, <0.001–0.622).

Conclusion:

Parents of children with DD in New York seemed highly willing for them to receive COVID-19 vaccines. Although few factors predicted willingness to vaccinate, addressing safety and developmental concerns regarding young children is warranted. Given their increased vulnerability, improved COVID-19 surveillance for children with DD is warranted.
Perinatal Physiological and Psychological Risk Factors and Childhood Sleep Outcomes: A Systematic Review and Meta-analysis
Authors: Dai Ying , Trout Kimberly Kovach , Liu Jianghong
Published: September 2022

Objectives:

The purpose of this study was to investigate the influence of maternal physiological and psychological factors during pregnancy and after birth on infant and children's sleep outcomes.

Methods:

Six databases were searched from inception to April 2021. Longitudinal studies that investigated the association of risk factors during and after pregnancy and children's sleep-related outcomes were included. Hedge's g and odds ratio were pooled as effect size with random effects model.

Results:

A total of 32 articles were included. Both prenatal maternal alcohol use (odds ratio [OR] = 1.85, 95% confidence interval [CI]: 1.04–3.28) and tobacco smoking (OR = 1.28, 95% CI: 1.01–1.62) were associated with shorter child sleep duration. Prenatal and postnatal maternal depression symptoms were associated with increased child sleep problems at age 6 months (OR = 1.97, 95% CI: 1.19–3.24, and 2.05, 95% CI: 1.37–3.07, respectively). Prenatal and postnatal maternal major depression disorders were associated with shorter sleep duration (Hedge's g = −0.97, 95% CI: −1.57 to −0.37) and lower sleep efficiency (Hedge's g = −1.44, 95% CI: −1.93 to −0.95). Prenatal anxiety had no impact on child sleep problems (OR = 1.34, 95% CI: 0.86–2.10).

Conclusion:

Maternal pregnancy and obstetric factors and psychological factors are potential risk factors of poor child sleep health. Future research is warranted to better understand the impact of these risk factors on long-term child sleep outcomes and their potential mediating mechanisms.
Vanadium in groundwater aquifers increases the risk of MAC pulmonary infection in O’ahu, Hawai’i
Authors: Lipner Ettie M. , French Joshua P. , Nelson Stephen , Falkinham III Joseph O. , Mercaldo Rachel A. , Blakney Rebekah A. , Daida Yihe G. , Frankland Timothy B. , Messier Kyle P. , Honda Jennifer R. , Honda Stacey , Prevots D. Rebecca
Published: September 2022

Rationale:

Hawai’i has the highest prevalence of nontuberculous mycobacterial (NTM) pulmonary disease in the United States. Previous studies indicate that certain trace metals in surface water increase the risk of NTM infection.

Objective:

To identify whether trace metals influence the risk of NTM infection in O’ahu, Hawai’i.

Methods:

A population-based ecologic cohort study was conducted using NTM infection incidence data from patients enrolled at Kaiser Permanente Hawai’i during 2005–2019. We obtained sociodemographic, microbiologic, and geocoded residential data for all Kaiser Permanente Hawai’i beneficiaries. To estimate the risk of NTM pulmonary infection from exposure to groundwater constituents, we obtained groundwater data from three data sources: (1) Water Quality Portal; (2) the Hawai’i Department of Health; and (3) Brigham Young University, Department of Geological Science faculty. Data were aggregated by an aquifer and were associated with the corresponding beneficiary aquifer of residence. We used Poisson regression models with backward elimination to generate models for NTM infection risk as a function of groundwater constituents. We modeled two outcomes: Mycobacterium avium complex (MAC) species and Mycobacterium abscessus group species.

Results:

For every 1-unit increase in the log concentration of vanadium in groundwater at the aquifer level, infection risk increased by 22% among MAC patients. We did not observe significant associations between water-quality constituents and infection risk among M. abscessus patients.

Conclusions:

Concentrations of vanadium in groundwater were associated with MAC pulmonary infection in O’ahu, Hawai’i. These findings provide evidence that naturally occurring trace metals influence the presence of NTM in water sources that supply municipal water systems.
Stony Brook University Hospital: Working Cleaner, Smarter
Authors: Gomes Carol A.
Published: September 2022

To protect the well-being of their communities and the planet, healthcare organizations must take the lead in correcting the negative impacts of their business on the environment by finding new ways to work cleaner and smarter. Stony Brook University Hospital has been recognized for making the commitment to develop and maintain sustainable practices—from the elimination of mercury to the efficient design of new facilities—that are good for the environment and good for business. With the participation of the entire organization, from the C-suites to the front lines, the results are measurably impressive.
Umbilical cord blood: an undervalued and underutilized resource in allogeneic hematopoietic stem cell transplant and novel cell therapy applications
Authors: Shi Patricia A. , Luchsinger Larry L. , Greally John M. , Delaney Colleen S.
Published: September 2022

Purpose of review

The purpose of this review is to primarily discuss the unwarranted decline in the use of umbilical cord blood (UCB) as a source of donor hematopoietic stem cells (HSC) for hematopoietic cell transplantation (HCT) and the resulting important implications in addressing healthcare inequities, and secondly to highlight the incredible potential of UCB and related birthing tissues for the development of a broad range of therapies to treat human disease including but not limited to oncology, neurologic, cardiac, orthopedic and immunologic conditions.

Recent findings

When current best practices are followed, unrelated donor umbilical cord blood transplant (CBT) can provide superior quality of life-related survival compared to other allogeneic HSC donor sources (sibling, matched or mismatched unrelated, and haploidentical) through decreased risks of relapse and chronic graft vs. host disease. Current best practices include improved UCB donor selection criteria with consideration of higher resolution human leukocyte antigen (HLA) typing and CD34+ cell dose, availability of newer myeloablative but reduced toxicity conditioning regimens, and rigorous supportive care in the early posttransplant period with monitoring for known complications, especially related to viral and other infections that may require intervention. Emerging best practice may include the use of ex vivo expanded single-unit CBT rather than double-unit CBT (dCBT) or ‘haplo-cord’ transplant, and the incorporation of posttransplant cyclophosphamide as with haploidentical transplant and/or incorporation of novel posttransplant therapies to reduce the risk of relapse, such as NK cell adoptive transfer. Novel, non-HCT uses of UCB and birthing tissue include the production of UCB-derived immune effector cell therapies such as unmodified NK cells, chimeric antigen receptor-natural killer cells and immune T-cell populations, the isolation of mesenchymal stem cells for immune modulatory treatments and derivation of induced pluripotent stem cells haplobanks for regenerative medicine development and population studies to facilitate exploration of drug development through functional genomics.

The potential of allogeneic UCB for HCT and novel cell-based therapies is undervalued and underutilized. The inventory of high-quality UCB units available from public cord blood banks (CBB) should be expanding rather than contracting in order to address ongoing healthcare inequities and to maintain a valuable source of cellular starting material for cell and gene therapies and regenerative medicine approaches. The expertise in Good Manufacturing Practice-grade manufacturing provided by CBB should be supported to effectively partner with groups developing UCB for novel cell-based therapies.
Use of polylactid acid membrane improves outcome of split-thickness skin graft donor sites: a prospective, comparative, randomized study
Authors: Moellhoff Nicholas , Lettner Maria , Frank Konstantin , Giunta Riccardo E. , Ehrl Denis
Published: September 2022

Background:

Polyurethane film (PU) dressings are commonly applied for coverage of split-thickness skin graft (SSG) donor sites, while previous studies have suggested reduced morbidity using a polylactic acid membrane (PLM). To further investigate the optimal treatment approach, the presented study compared outcome of donor sites in patients receiving either PLM or PU.

Methods:

This randomized clinical trial allocated patients requiring SSG to receive either PLM or PU at the donor-site. Primary endpoint was difference in donor site scar appearance between groups 3 months postoperatively (Vancouver Scar Scale – VSS). Secondary endpoints included pain, the number of and time requried for wound dressing changes, and costs related to the wound dressing.

Results:

30 patients were allocated to each group. The median VSS scored lower for patients receiving PLM (PU: 3 (Q1: 2; Q3: 4) vs. PLM: 2 (Q1: 1; Q3: 3); p=0.049). Pain during change of wound dressing (PU: 2.0 ± 0.2 vs. PLM: 0.5 ± 0.2; p<0.001) and mobilization (PU: 0.8 ± 0.2 vs. PLM: 0.3 ± 0.1; p=0.032) was reduced in the PLM group. Patients with PLM required less dressing changes per day of hospital stay (PU: 0.44 ± 0.06 vs. PLM: 0.28 ± 0.02; p=0.015). Mean time for wound dressing changes per patient was higher in the PU group (PU: 74.50 ± 5.72 vs. PLM: 21.43 ± 2.61 min; p<0.001). Costs were higher in the PLM group (PU: 67.83 ± 5.56 vs. PLM: 162.79 ± 21.76 €; p<0.001).

Conclusions:

PLM improves outcome of SSG donor sites, however, higher treatment costs must be taken into consideration.
20 Years of Abdominal Wall Allotransplantation - A Systematic Review of the Short and Long-Term Outcomes with a View to Future Modifications
Authors: Reed Laura T. , Echternacht Scott R. , Shanmugarajah Kumaran , Hernandez Roberto , Langstein Howard N. , Leckenby Jonathan I.
Published: September 2022

Background:

Abdominal wall allotransplant (AWA) following intestinal and multivisceral transplant procedures has proven to be successful in achieving adequate closure in patients where other techniques have proven inadequate. Thus far, the focus of these AWAs has been on graft and overall patient survival following surgery and the implementation of immunosuppression.

Objectives:

The purpose of this study is to review the outcomes of AWA reported in the literature.

Data Sources:

The PubMed database was queried, and 2595 articles were found. Search criteria used were “abdominal wall transplant” and “abdominal wall allotransplant.” Of these, 8 met inclusion/exclusion criteria.

Results:

In the present study, 8 publications were identified reporting AWAs, for a total of 38 full-thickness AWAs done worldwide. All studies reported AWA in combination with visceral organ allotransplantation (VOA). AWAs reported thus far have been non-neurotized.

Discussion:

AWAs have proven to be beneficial both in terms of abdominal wall closure as well as acting as a sentinel marker for rejection for underlying VOAs. The success of AWAs and their long-term survival has introduced the question of functionality and long-term durability. Cadaveric studies have shown it is possible to neurotize AWAs, and future direction toward neurotized AWAs requires tools to assess functional outcomes of these transplants.

Conclusions and Implications:

AWA is an important reconstructive option when abdominal wall closure is challenging and should be considered in combination with VOAs. There may be potential benefit in neurotizing the AWA for functional use, and future studies should aim to include functional outcomes.
Update on pathogenesis, management, and control of Plasmodium vivax
Authors: Khan Nazia , Daily Johanna P.
Published: September 2022

Purpose of review

This is a review of Plasmodium vivax epidemiology, pathogenesis, disease presentation, treatment and innovations in control and elimination. Here, we examine the recent literature and summarize new advances and ongoing challenges in the management of P. vivax.

Recent findings

P. vivax has a complex life cycle in the human host which impacts disease severity and treatment regimens. There is increasing data for the presence of cryptic reservoirs in the spleen and bone marrow which may contribute to chronic vivax infections and possibly disease severity. Methods to map the geospatial epidemiology of P. vivax chloroquine resistance are advancing, and they will inform local treatment guidelines. P. vivax treatment requires an 8-aminoquinoline to eradicate the dormant liver stage. Evidence suggests that higher doses of 8-aminoquinolines may be needed for radical cure of tropical frequent-relapsing strains.

P. vivax is a significant global health problem. There have been recent developments in understanding the complexity of P. vivax biology and optimization of antimalarial therapy. Studies toward the development of best practices for P. vivax control and elimination programs are ongoing.
An Ectopic Parathyroid Adenoma Mimicking Submandibular Gland on 99mTc-MIBI Parathyroid Scintigraphy
Authors: Chen Meijie , Chen Song , Li Xuena , Li Yaming
Published: September 2022

A 67-year-old woman complained of continuous low back pain for 4 months. She was referred for a 99mTc-MIBI parathyroid scintigraphy with neck SPECT/CT imaging. The planar images showed no abnormal uptake. However, on the SPECT/CT scan, a soft tissue nodule with high uptake was noted adjacent to the left submandibular gland, mimicking normal submandibular gland uptake. Pathological examination from surgical specimen showed that it was an ectopic parathyroid adenoma.
Optimal Timing of Perioperative Chemoprophylaxis in Patients With High Thromboembolic Risk Undergoing Major Abdominal Surgery
Authors: Liu David S. , Stevens Sean G. , Watson David I. , Goh Su Kah , Muralidharan Vijayaragavan , Wong Enoch , Fong Jonathan , Wong Darren J. ,   PROTECTinG Investigators,   VERITAS Collaborative
Published: September 2022

Objective:

To determine whether early (before skin closure) versus postoperative chemoprophylaxis affects the incidence of venous thromboembolism (VTE) and bleeding following major abdominal surgery, in a high thromboembolic risk population.

Background:

Major abdominal surgery incurs both VTE and bleeding risks. Patients with high preoperative VTE risk derive the most benefit from chemoprophylaxis, but carry an increased risk of bleeding. The optimal window for chemoprophylaxis in the perioperative period, whereby both VTE and bleeding risks are minimized, is unknown.

Methods:

Analysis of pooled data from 5 multicenter studies including only high thromboembolic risk (Caprini score >4) patients. Clinical VTE was defined as radiographically proven symptomatic disease <30 days postsurgery. Major bleeding was defined as the need for blood transfusion, reintervention, or >20 g/L fall in hemoglobin.

Results:

From 5501 cases, chemoprophylaxis was initiated early in 1752 (31.8%) patients and postoperatively in 3749 (68.2%) patients. Baseline characteristics were similar between study groups. The incidence of clinical VTE was not associated with chemoprophylaxis timing [early 0.7% vs. postop 0.7%, odds ratio (OR): 1.11, 95% confidence interval (CI): 0.60–2.15, P=0.730]. Contrastingly, compared with postoperative chemoprophylaxis, early usage increased the risk of all bleeding (5.1% vs. 2.6%, OR: 2.04, 95% CI: 1.52–2.73, P<0.001) major bleeding (3.6% vs. 1.8%, OR: 1.99, 95% CI: 1.40–2.81, P<0.001), and reintervention (2.0% vs. 1.0%, OR: 2.10, 95% CI: 1.32–3.35, P=0.003). Early chemoprophylaxis independently predicted postoperative bleeding (OR: 1.71, 95% CI: 1.25–2.34, P<0.001), but not VTE.

Conclusions:

In high VTE risk patients undergoing major abdominal surgery, chemoprophylaxis commenced postoperatively reduces bleeding risk without affecting clinical VTE risk.
The role of booster vaccination and ongoing viral evolution in seasonal circulation of SARS-CoV-2
Authors: Kraay A. N. M. , Gallagher M. E. , Ge Y. , Han P. , Baker J. M. , Koelle K. , Handel A. , Lopman B. A.
Published: September 2022

Periodic resurgences of COVID-19 in the coming years can be expected, while public health interventions may be able to reduce their intensity. We used a transmission model to assess how the use of booster doses and non-pharmaceutical interventions (NPIs) amid ongoing pathogen evolution might influence future transmission waves. We find that incidence is likely to increase as NPIs relax, with a second seasonally driven surge expected in autumn 2022. However, booster doses can greatly reduce the intensity of both waves and reduce cumulative deaths by 20% between 7 January 2022 and 7 January 2023. Reintroducing NPIs during the autumn as incidence begins to increase again could also be impactful. Combining boosters and NPIs results in a 30% decrease in cumulative deaths, with potential for greater impacts if variant-adapted boosters are used. Reintroducing these NPIs in autumn 2022 as transmission rates increase provides similar benefits to sustaining NPIs indefinitely (307 000 deaths with indefinite NPIs and boosters compared with 304 000 deaths with transient NPIs and boosters). If novel variants with increased transmissibility or immune escape emerge, deaths will be higher, but vaccination and NPIs are expected to remain effective tools to decrease both cumulative and peak health system burden, providing proportionally similar relative impacts.