Rituximab administration in pediatric patients with newly diagnosed acute lymphoblastic leukemia.

Polyethylene glycol (PEG)-asparaginase (pegaspargase) is a key agent in chemotherapy for acute lymphoblastic leukemia (ALL), but recipients frequently experience allergic reactions. We hypothesized that by decreasing antibody-producing CD20-positive B cells, rituximab may reduce these reactions. Children and adolescents (aged 1-18 years) with newly diagnosed B-ALL treated on the St. Jude Total XVII study were randomized to induction therapy with or without rituximab on day 3 (cohort 1) or on days 6 and 24 (cohort 2). Patient clinical demographics, CD20 expression, minimal residual disease (MRD), rituximab reactions, pegaspargase allergy, anti-pegaspargase antibodies, and pancreatitis were evaluated. Thirty-five patients received rituximab and 37 did not. Among the 35 recipients, 16 (45.7%) experienced a grade 2 or higher reaction to rituximab. There were no differences between recipients and non-recipients in the incidence of pegaspargase reactions (P > 0.999), anti-pegaspargase antibodies (P = 0.327), or pancreatitis (P = 0.480). CD20 expression on day 8 was significantly lower in rituximab recipients (P < 0.001), but there were no differences in MRD levels on day 8, 15, or at the end of induction. Rituximab administration during induction in pediatric patients with B-ALL was associated with a high incidence of infusion reactions with no significant decrease in pegaspargase allergies, anti-pegaspargase antibodies, or MRD.

T cell repertoire analysis suggests a prominent bystander response in human cardiac allograft vasculopathy.

T cells are implicated in the pathogenesis of cardiac allograft vasculopathy (CAV), yet their clonality, specificity, and function are incompletely defined. Here we used T cell receptor ß chain (TCRB) sequencing to study the T cell repertoire in the coronary artery, endomyocardium, and peripheral blood at the time of retransplant in four cases of CAV and compared it to the immunoglobulin heavy chain variable region (IGHV) repertoire from the same samples. High-dimensional flow cytometry coupled with single-cell PCR was also used to define the T cell phenotype. Extensive overlap was observed between intragraft and blood TCRBs in all cases, a finding supported by robust quantitative diversity metrics. In contrast, blood and graft IGHV repertoires from the same samples showed minimal overlap. Coronary infiltrates included CD4+ and CD8+ memory T cells expressing inflammatory (IFNγ, TNFα) and profibrotic (TGFß) cytokines. These were distinguishable from the peripheral blood based on memory, activation, and tissue residency markers (CD45RO, CTLA-4, and CD69). Importantly, high-frequency rearrangements were traced back to endomyocardial biopsies (2-6 years prior). Comparison with four HLA-mismatched blood donors revealed a repertoire of shared TCRBs, including a subset of recently described cross-reactive sequences. These findings provide supportive evidence for an active local intragraft bystander T cell response in late-stage CAV.

Preserving and advocating for essential care for women during the coronavirus disease 2019 pandemic.

The coronavirus disease 2019 pandemic has redefined "essential care," and reproductive healthcare has become a frequently targeted and debated topic. As obstetricians and gynecologists, we stand with our patients and others as advocates for women's reproductive health. With the medical and surgical training to provide all aspects of reproductive healthcare, obstetricians and gynecologists are indispensable and uniquely positioned to advocate for the full spectrum of care that our patients need right now. All patients have a right to these services. Contraception and abortion care remain essential, and we need to work at the local, state, and federal levels on policies that preserve these critical services. We must also support policies that will promote expansion of care, including lengthening Medicaid pregnancy and postpartum coverage. Although we continue to see patients, this is the time to engage outside clinical encounters by participating in lobbying and other advocacy efforts to preserve essential services, protecting the health, life, and welfare of our patients during the coronavirus disease 2019 pandemic.

Probing the subcellular distribution of phosphatidylinositol reveals a surprising lack at the plasma membrane.

The polyphosphoinositides (PPIn) are central regulatory lipids that direct membrane function in eukaryotic cells. Understanding how their synthesis is regulated is crucial to revealing these lipids' role in health and disease. PPIn are derived from the major structural lipid, phosphatidylinositol (PI). However, although the distribution of most PPIn has been characterized, the subcellular localization of PI available for PPIn synthesis is not known. Here, we used several orthogonal approaches to map the subcellular distribution of PI, including localizing exogenous fluorescent PI, as well as detecting lipid conversion products of endogenous PI after acute chemogenetic activation of PI-specific phospholipase and 4-kinase. We report that PI is broadly distributed throughout intracellular membrane compartments. However, there is a surprising lack of PI in the plasma membrane compared with the PPIn. These experiments implicate regulation of PI supply to the plasma membrane, as opposed to regulation of PPIn-kinases, as crucial to the control of PPIn synthesis and function at the PM.

Psychological distress and self-rated health status in reproductive aged women with pain: findings from a national, cross-sectional survey.

BACKGROUND: Pain impacts upon psychological wellbeing. In pregnant and postpartum women psychological distress may negatively affect the mother-infant relationship and lead to adverse infant development. Yet, co-occurrence of pain with psychological distress in women of reproductive age has not been investigated. Therefore, this study aimed to: 1) assess prevalence of psychological distress in reproductive aged women by pain severity; and 2) examine the self-rated health status of reproductive aged women with and without pain. METHOD: Data for women aged 18-49 years were obtained from the 2011-12 Australian Bureau of Statistics National Health Survey. Sample data were weighted to give population estimates. Recent pain severity, self-rated health and psychological distress were analysed for pregnant, breastfeeding and non-pregnant/non-breastfeeding women. RESULTS: Moderate-to-very severe pain was reported by 17.6% of pregnant (sample n = 165, weighted N = 191,856), 25.9% of breastfeeding (sample n = 210, weighted N = 234,601) and 23.9% of non-pregnant/non-breastfeeding women (sample n = 4005, weighted N = 4,607,140). Psychological distress was associated with pain in non-pregnant/non-breastfeeding women (p < 0.001). High-to-very high distress was seen in 26.4% (95% CI, 23.2-29.6) of NP/NBF, 8.1% (95% CI, 0-17.2) of breastfeeding and 7.3% (95% CI, 0-18.0) of pregnant women with moderate-to-very severe pain. Self-rated health status was associated with pain severity in pregnant (p = 0.001) and non-pregnant/non-breastfeeding (p < 0.001) women. CONCLUSION: Given the strong association between psychological distress and pain in non-pregnant/non-breastfeeding women, and the relatively common occurrence of moderate-to-very severe pain in both pregnant and breastfeeding women, assessment of psychological distress levels in all women of reproductive age who report experiencing moderate-to-very severe levels of pain may be of benefit.

Chronic pain, pain severity and analgesia use in Australian women of reproductive age.

BACKGROUND: The increasing prevalence and adverse outcomes associated with opioid analgesia use in women of reproductive age have become a significant public health issue internationally, with use during pregnancy potentially affecting maternal and infant health outcomes. OBJECTIVE: This study aims to provide national estimates of chronic pain, pain severity and analgesia use in Australian women of reproductive age by pregnancy status. METHOD: Data were obtained from the Australian Bureau of Statistics 2011-12 National Health Survey (n=20,426). Weighting was applied to sample data to obtain population estimates. For this study data were analysed for pregnant (n=166, N=192,617) and non-pregnant women (n=4710, N=5,256,154) of reproductive age (15-49 years). RESULTS: Chronic or reoccurring pain was reported in 5.1% of pregnant women and 9.7% of non-pregnant women, and 0.7% and 2.6% of pregnant and non-pregnant women reported recent opioid analgesia use respectively. Moderate-to-very severe pain was more common in pregnant than non-pregnant women taking opioid analgesics, and no pain and very mild-to-mild pain in non-pregnant women. CONCLUSION: Approximately 1 in 20 pregnant Australian women have chronic or reoccurring pain. Opioid analgesia was used by around 1% of Australian pregnant women during a two-week period, with use associated with moderate-to-very severe pain. Given that the safety of many analgesic medications in pregnancy remains unknown, pregnant women and health professionals require accurate, up-to-date information on the risks and benefits of analgesic use during pregnancy. Further evidence on the decision-making processes of pregnant women with pain should assist health professionals maximise outcomes for mothers and infants.

Does measuring body weight impact subsequent response to eating behavior questions?

OBJECTIVES: If being weighed impacts perceptions of eating behavior, it is important that the order of questionnaires and weighing be considered in research and practice. A quasi-experimental study was performed to examine whether being weighed immediately prior to completing a questionnaire affects responses to eating behavior questions. It was hypothesized that being weighed would serve as a priming stimulus and increase measures of dietary restraint, disinhibition, and hunger. METHODS: Trained researchers collected a sample of volunteers (n = 355) in 8 locations in the United States on two Saturdays in the summer of 2011. Half of the participants were weighed immediately prior to completing the Three Factor Eating Questionnaire (TFEQ), with the remaining half weighed immediately after TFEQ completion. RESULTS: A priori hypotheses were not supported despite replicating known relationships between weight, dietary restraint and disinhibition. Results indicated that being weighed first produced a difference in differences on disinhibition scores between low restraint score (95% CI = 4.65-6.02) and high restraint score (95% CI = 6.11-7.57) compared to being weighed after questionnaire completion (p = 0.003). However, this relationship was not significant when modeling restraint as a continuous variable, questioning the use of dichotomization. CONCLUSIONS: Being weighed is unlikely to be a strong enough prime to significantly change scores on eating behavior questionnaires for everyone, but may allow differences in restraint status to become more evident. Researchers assessing dietary restraint should be wary of the possibility of producing different results when treating restraint as continuous or dichotomous, which could lead to different interpretations.