Does Failure to Rescue Drive Race/Ethnicity-based Disparities in Survival After Heart Transplantation?

OBJECTIVE: The objective was to assess whether race/ethnicity is an independent predictor of failure to rescue (FTR) after orthotopic heart transplantation (OHT). SUMMARY BACKGROUND DATA: Outcomes following OHT vary by patient level factors; for example, non-White patients have worse outcomes than White patients after OHT. Failure to rescue is an important factor associated with cardiac surgery outcomes, but its relationship to demographic factors is unknown. METHODS: Using the United Network for Organ Sharing database, we included all adult patients who underwent primary isolated OHT between 1/1/2006 snd 6/30/2021. FTR was defined as the inability to prevent mortality after at least one of the UNOS-designated postoperative complications. Donor, recipient, and transplant characteristics, including complications and FTR, were compared across race/ethnicity. Logistic regression models were created to identify factors associated with complications and FTR. Kaplan Meier and adjusted Cox proportional hazards models evaluated the association between race/ethnicity and posttransplant survival. RESULTS: There were 33,244 adult, isolated heart transplant recipients included: the distribution of race/ethnicity was 66% (n=21,937) White, 21.2% (7,062) Black, 8.3% (2,768) Hispanic, and 3.3% (1,096) Asian. The frequency of complications and FTR differed significantly by race/ethnicity. After adjustment, Hispanic recipients were more likely to experience FTR than White recipients (OR 1.327, 95% CI[1.075-1.639], P =0.02). Black recipients had lower 5-year survival compared with other races/ethnicities (HR 1.276, 95% CI[1.207-1.348], P <0.0001). CONCLUSIONS: In the US, Black recipients have an increased risk of mortality after OHT compared with White recipients, without associated differences in FTR. In contrast, Hispanic recipients have an increased likelihood of FTR, but no significant mortality difference compared with White recipients. These findings highlight the need for tailored approaches to addressing race/ethnicity-based health inequities in the practice of heart transplantation.

The bacillithiol pathway is required for biofilm formation in Staphylococcus aureus.

Staphylococcus aureus is a major human pathogen that can cause infections that range from superficial skin and mucosal infections to life threatening disseminated infections. S. aureus can attach to medical devices and host tissues and form biofilms that allow the bacteria to evade the host immune system and provide protection from antimicrobial agents. To counter host-generated oxidative and nitrosative stress mechanisms that are part of the normal host responses to invading pathogens, S. aureus utilizes low molecular weight (LMW) thiols, such as bacillithiol (BSH). Additionally, S. aureus synthesizes its own nitric oxide (NO), which combined with its downstream metabolites may also protect the bacteria against specific host responses. We have previously shown that LMW thiols are required for biofilm formation in Mycobacterium smegmatis and Pseudomonas aeruginosa. Here, we show that the S. aureus bshC mutant strain, which is defective in the last step of the BSH pathway and lacks BSH, is impaired in biofilm formation. We also identify a possible S-nitrosobacillithiol reductase (BSNOR), similar in sequence to an S-nitrosomycothiol reductase found in M. smegmatis and show that the putative S. aureus bsnoR mutant strain has reduced levels of BSH and decreased biofilm formation. Our studies also show that NO plays an important role in biofilm formation and that acidified sodium nitrite severely reduces biofilm thickness. These studies provide insight into the roles of oxidative and nitrosative stress mechanisms on biofilm formation and indicate that BSH and NO are key players in normal biofilm formation in S. aureus.

"I see it very much as an end-of-life food" - Barriers to oral nutritional supplement adherence, views from healthy older adults.

Malnutrition affects approximately one quarter of UK adults aged 65 years and over. As the global demographic shift continues, malnutrition is expected to increase. Oral nutritional supplements (ONS) are used both to prevent and to treat malnutrition. However, their effectiveness is compromised by poor adherence, and it is not well understood what contributes to this. Therefore, the current research was designed to explore ONS adherence from the parallel perspectives of ONS as a prescribed "medication" and as a food supplement/substitute. Eighteen older adults (13F, 5M; mean age = 73.4 yr; range: 70-80 yr) participated in focus groups (three in-person and one online), to investigate experiences of taking prescribed medications, including dietary supplements, and what should be factors to consider in supporting regular intake of ONS for trial development, as well as any potential improvements to products. Focus group sessions were recorded and then transcribed. Thematic Analysis was applied to the transcripts by the first author, and themes were discussed in depth, using exemplar quotes from participants. Five dominant themes were identified from the data: Disgust, Palatability and Acceptance; End-of-Life Care; Resistance to Medicines; Rituals and Reminders; and Real Food Displacement. Nutritional supplements were characterised as "disgusting", "manufactured", and associated with serious, chronic illness, as well as end-of-life care, in contrast to probiotics which were linked with health and wellness. The sweet taste of ONS was identified as a barrier to intake, given that it is generally associated with a signal to stop eating, and low hunger. As a group, participants tried to "avoid taking medicines", and viewed the need to have them negatively, yet most regularly took prescribed medication and/or vitamin supplements. Participants identified several, rituals and reminders to take medicines, including meal-based, or time-of-day-based prompts (e.g., before, with or after meals). To improve adherence, savoury products were suggested, as well as a more person-centred approach to individual nutritional needs and preferences. Overall, the group discussion mainly identified barriers to intake, but that improving taste, adding to "real food" (not replacing meals), and offering variety of flavour and form (e.g., savoury soups as well as sweet drinks) could be included in future trials to improve appeal and therefore intake. Future work should continue to explore how best to formulate, market and/or prescribe ONS, and how this might vary for malnutrition prevention vs treatment strategies.

BET bromodomain inhibitors regulate keratinocyte plasticity.

Although most acute skin wounds heal rapidly, non-healing skin ulcers represent an increasing and substantial unmet medical need that urgently requires effective therapeutics. Keratinocytes resurface wounds to re-establish the epidermal barrier by transitioning to an activated, migratory state, but this ability is lost in dysfunctional chronic wounds. Small-molecule regulators of keratinocyte plasticity with the potential to reverse keratinocyte malfunction in situ could offer a novel therapeutic approach in skin wound healing. Utilizing high-throughput phenotypic screening of primary keratinocytes, we identify such small molecules, including bromodomain and extra-terminal domain (BET) protein family inhibitors (BETi). BETi induce a sustained activated, migratory state in keratinocytes in vitro, increase activation markers in human epidermis ex vivo and enhance skin wound healing in vivo. Our findings suggest potential clinical utility of BETi in promoting keratinocyte re-epithelialization of skin wounds. Importantly, this novel property of BETi is exclusively observed after transient low-dose exposure, revealing new potential for this compound class.

Impact of donor-recipient age-difference in adolescent heart transplantation.

INTRODUCTION: The relationship between donor age and adolescent heart transplant outcomes remains incompletely understood. We aimed to explore the effect of donor-recipient age difference on survival after adolescent heart transplantation. METHODS: The United Network for Organ Sharing database was used to identify 2,855 adolescents aged 10-17 years undergoing isolated primary heart transplantation from 1/1/2000 to 12/31/2022. The primary outcome was 10-year post-transplant survival. Multivariable Cox regression identified predictors of mortality after adjusting for donor and recipient characteristics. A restricted cubic spline assessed the non-linear association between donor-recipient age-difference and the adjusted relative mortality hazard. RESULTS: The median donor-recipient age-difference was +3 (range -13 to +47) years, and 17.7% (n = 504) of recipients had an age- difference > 10 years. Recipients with an age-difference > 10 years had a less favorable pre-transplant profile, including a higher incidence of priority status 1A (81.6%, n = 411 vs. 73.6%, n = 1730; p = .01). The 10-year survival rate was 54.6% (95% confidence interval (CI) 48.8- 60.4) among recipients with a donor-recipient age-difference > 10 years and 66.9% (95% CI: 64.4-69.4) among those with an age-difference ≤10 years. An age-difference > 10 years was an independent predictor of mortality (hazard ratio 1.43, 95% CI: 1.18-1.72, p < .001). Spline analysis demonstrated that the adjusted mortality hazard increased with increasingly positive donor-recipient age-difference and became significantly higher at an age-difference of 11 years. CONCLUSION: A donor-recipient age-difference > 11 years is independently associated with higher long-term mortality after adolescent heart transplantation. This finding may help inform acceptable donor selection practice for adolescent heart transplant candidates.

Repeat pediatric heart transplantation: A united network for organ sharing database analysis.

BACKGROUND: A history of congenital heart disease and previous transplantation are each independently associated with worse survival following pediatric heart transplantation. This study aimed to evaluate the characteristics and outcomes of children undergoing repeat heart transplantation in the United States based on the underlying diagnosis. METHODS: The United Network for Organ Sharing database was used to identify 8111 patients aged <18 years undergoing isolated heart transplantation from 2000 to 2021, including 435 (5.4%) repeat transplants. Restricted cubic spline analysis assessed the non-linear relationship between inter-transplant interval and the primary outcome of all-cause mortality or re-transplantation. Multivariable Cox regression assessed the impact of re-transplantation on the primary outcome. Median follow-up was 5.0 (interquartile range 1.9-9.9) years. RESULTS: Repeat transplant patients were older (median age 12 vs. 4 years; p < .001), and less likely to be in UNOS status 1A (66.0%, n = 287 vs. 81.0% n = 6217; p < .001) than primary transplant patients. Freedom from the primary outcome was 51.4% (95% confidence interval [CI] 45.5-57.2) among repeat transplants and 70.5% (95% CI 69.2-71.8) among primary transplants at 10 years (p < .001). Among repeat transplant patients, the relative hazard of the primary outcome became non-significant when the inter-transplant interval >3.6 years. Congenital heart disease was an independent predictor of mortality among primary (HR 1.8, 95% CI 1.6-1.9) but not repeat transplant (HR 1.1, 95% CI .8-1.6) patients. CONCLUSIONS: Long-term outcomes remain poor for patients undergoing repeat heart transplantation, particularly those with an inter-transplant interval <3.6 years. Underlying diagnosis does not impact outcomes after repeat transplantation, after accounting for other risk factors.

Effects of cueing multiple memories of eating on people's judgments about their diet.

Past research shows that recalling a single positive health-related experience, such as exercising, can encourage people's subsequent healthy behaviours. In contrast, we reasoned that attempting to recall many healthy experiences might elicit a metacognitive experience of difficulty that would lead people to perceive themselves as less healthy, and perhaps to make other health-related judgments based on this perception. In two pre-registered experiments (combined N = 729), participants recalled either "few" or "many" instances of eating either healthily or unhealthily, before rating the healthiness of their diets and completing measures of their eating preferences and choices. Contrary to our predictions, our pre-registered analyses provided minimal evidence that the number of memories people retrieved affected their judgments. However, exploratory mediation analyses suggested that two counteracting effects may have occurred, whereby retrieving more (un)healthy memories led people to identify as more (un)healthy, yet also created a sense of subjective difficulty that partially or wholly negated these effects. These findings suggest that whereas probing people's dietary memories might sometimes lead to healthier self-perceptions and dietary choices, we should also consider the possibility of backfire effects.

The effect of intranasal insulin on appetite and mood in women with and without obesity: an experimental medicine study.

BACKGROUND/OBJECTIVES: Intranasal (IN) administration of insulin decreases appetite in humans, but the underlying mechanisms are unclear, and it is unknown whether IN insulin affects the food intake of women with obesity. SUBJECTS/METHODS: In a double-blind, placebo-controlled, crossover design, participants (35 lean women and 17 women with obesity) were randomized to receive 160 IU/1.6 mL of IN insulin or placebo in a counterbalanced order in the post prandial state. The effects of IN insulin on cookie intake, appetite, mood, food reward, cognition and neural activity were assessed. RESULTS: IN insulin in the post prandial state reduced cookie intake, appetite and food reward relative to placebo and these effects were more pronounced for women with obesity compared with lean women. IN insulin also improved mood in women with obesity. In both BMI groups, IN insulin increased neural activity in the insula when viewing food pictures. IN insulin did not affect cognitive function. CONCLUSIONS: These results suggest that IN insulin decreases palatable food intake when satiated by reducing food reward and that women with obesity may be more sensitive to this effect than lean women. Further investigation of the therapeutic potential of IN insulin for weight management in women with obesity is warranted.

White Coat Hypertension Persistence in Children and Adolescents: The Pediatric Nephrology Research Consortium Study.

OBJECTIVES: To determine whether youth with white coat hypertension on initial ambulatory blood pressure monitoring (ABPM) continue to demonstrate the same pattern on repeat ABPM. STUDY DESIGN: Retrospective longitudinal cohort study of patients referred for high blood pressure (BP) and diagnosed with white coat hypertension by ABPM who had follow-up ABPM 0.5-4.6 years later at 11 centers in the Pediatric Nephrology Research Consortium. We classified ABPM phenotype using the American Heart Association guidelines. At baseline, we classified those with hypertensive BP in the clinic as "stable white coat hypertension," and those with normal BP as "intermittent white coat hypertension." We used multivariable generalized linear mixed effect models to estimate the association of baseline characteristics with abnormal ABPM phenotype progression. RESULTS: Eighty-nine patients met the inclusion criteria (median age, 13.9 years; 78% male). Median interval time between ABPM measurements was 14 months. On follow-up ABPM, 61% progressed to an abnormal ABPM phenotype (23% ambulatory hypertension, 38% ambulatory prehypertension). Individuals age 12-17 years and those with stable white coat hypertension had greater proportions progressing to either prehypertension or ambulatory hypertension. In the multivariable models, baseline wake systolic BP index ≥0.9 was significantly associated with higher odds of progressing to ambulatory hypertension (OR 3.07, 95% CI 1.02-9.23). CONCLUSIONS: The majority of the patients with white coat hypertension progressed to an abnormal ABPM phenotype. This study supports the 2017 American Academy of Pediatrics Clinical Practice Guideline's recommendation for follow-up of ABPM in patients with white coat hypertension.

Progress and challenges in sorghum biotechnology, a multipurpose feedstock for the bioeconomy.

Sorghum [Sorghum bicolor (L.) Moench] is the fifth most important cereal crop globally by harvested area and production. Its drought and heat tolerance allow high yields with minimal input. It is a promising biomass crop for the production of biofuels and bioproducts. In addition, as an annual diploid with a relatively small genome compared with other C4 grasses, and excellent germplasm diversity, sorghum is an excellent research species for other C4 crops such as maize. As a result, an increasing number of researchers are looking to test the transferability of findings from other organisms such as Arabidopsis thaliana and Brachypodium distachyon to sorghum, as well as to engineer new biomass sorghum varieties. Here, we provide an overview of sorghum as a multipurpose feedstock crop which can support the growing bioeconomy, and as a monocot research model system. We review what makes sorghum such a successful crop and identify some key traits for future improvement. We assess recent progress in sorghum transformation and highlight how transformation limitations still restrict its widespread adoption. Finally, we summarize available sorghum genetic, genomic, and bioinformatics resources. This review is intended for researchers new to sorghum research, as well as those wishing to include non-food and forage applications in their research.

CPSF3-dependent pre-mRNA processing as a druggable node in AML and Ewing's sarcoma.

The post-genomic era has seen many advances in our understanding of cancer pathways, yet resistance and tumor heterogeneity necessitate multiple approaches to target even monogenic tumors. Here, we combine phenotypic screening with chemical genetics to identify pre-messenger RNA endonuclease cleavage and polyadenylation specificity factor 3 (CPSF3) as the target of JTE-607, a small molecule with previously unknown target. We show that CPSF3 represents a synthetic lethal node in a subset of acute myeloid leukemia (AML) and Ewing's sarcoma cancer cell lines. Inhibition of CPSF3 by JTE-607 alters expression of known downstream effectors in AML and Ewing's sarcoma lines, upregulates apoptosis and causes tumor-selective stasis in mouse xenografts. Mechanistically, it prevents the release of newly synthesized pre-mRNAs, resulting in read-through transcription and the formation of DNA-RNA hybrid R-loop structures. This study implicates pre-mRNA processing, and specifically CPSF3, as a druggable target providing an avenue to therapeutic intervention in cancer.

Author Correction: CPSF3-dependent pre-mRNA processing as a druggable node in AML and Ewing's sarcoma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Frequency of fruit consumption and savoury snacking predict psychological health; selective mediation via cognitive failures.

While there is growing interest in the link between diet and psychological health, there is a surprising lack of studies investigating the precise associations between nutrient-rich foods (such as fruit and vegetables) versus nutrient-poor foods (such as energy-dense savoury and sweet snacks), and psychological health. Similarly, the psychological processes underpinning the relationship between dietary intake and psychological health remain unclear. Hence, the present study aimed to explore the relationship between dietary consumption and psychological health, with cognitive processes as a theoretical mediator. This cross-sectional online study included 428 healthy adults (53% female; mean age= 39.7, SD= 13.0), with participants completing a range of validated questionnaires measuring dietary habits and psychological health. Stepwise multiple regression revealed that more frequent consumption of fruit was associated with reduced symptoms of depression (ß = -.109, p = 0.025) and greater positive psychological wellbeing (ß = .187, p < 0.001). Conversely, more frequent savoury snacking was associated with increased anxiety (ß = .127, p = 0.005). Further, mediation analyses revealed that more frequent consumption of savoury snacks was associated with increased symptoms of depression, stress, anxiety, and reduced psychological wellbeing, via an increase in cognitive failures (ps < 0.001). These results provide new insights on the independent associations between certain types of food and psychological health, and the psychological mechanisms that may mediate these. Further work is now required to establish causality and determine whether these may represent modifiable dietary targets that can directly (and indirectly) influence our psychological health.

Adjunct Use of Continuous Renal Replacement Therapy with Extracorporeal Membrane Oxygenation Achieves Negative Fluid Balance and Enhances Oxygenation Which Improves Survival in Critically Ill Patients without Kidney Failure.

INTRODUCTION: Fluid overload in extracorporeal membrane oxygenation (ECMO) patients has been associated with increased mortality. Patients receiving ECMO and continuous renal replacement therapy (CRRT) who achieve a negative fluid balance have improved survival. Limited data exist on the use of CRRT solely for fluid management in ECMO patients. METHODS: We performed a single-center retrospective review of 19 adult ECMO patients without significant renal dysfunction who received CRRT for fluid management. These patients were compared to a cohort of propensity-matched controls. RESULTS: After 72 h, the treatment group had a fluid balance of -3840 mL versus + 425 mL (p ≤ 0.05). This lower fluid balance correlated with survival to discharge (odds ratio 2.54, 95% confidence interval 1.10-5.87). Improvement in the ratio of arterial oxygen content to fraction of inspired oxygen was also significantly higher in the CRRT group (102.4 vs. 0.7, p ≤ 0.05). We did not observe any significant difference in renal outcomes. CONCLUSIONS: The use of CRRT for fluid management is effective and, when resulting in negative fluid balance, improves survival in adult ECMO patients without significant renal dysfunction.

Front-of-pack health imagery on both 'healthy' and 'unhealthy' foods leads people to misremember seeing health claims: Two memory experiments.

Front-of-pack health imagery can shape people's inferences about food products' health benefits, even leading people to falsely remember reading health claims they never saw. However, research has typically examined these effects in situations where participants have little contextual information to guide their inferences about a product. The present research aimed to replicate the finding that front-of-pack health imagery leads participants to falsely remember reading health claims. It also extends that finding, by exploring whether this effect is moderated by the presence of contextual information signaling the product's actual 'healthiness'. In two pre-registered experiments, participants saw images of fictitious food products accompanied by written nutrition claims. Some of the products contained a health-related image whereas others did not. The supposed 'healthiness' of each product was manipulated by altering the color of the products' multiple traffic light (MTL) label (Experiment 1), or with an explicit healthiness statement (Experiment 2). Participants then attempted to remember the written claims that had appeared on each product's packaging. Health-related images increased participants' tendency to falsely remember reading health claims. But this was true regardless of whether or not participants saw contextual cues about the products' healthiness, either indirectly (Experiment 1) or directly (Experiment 2). These findings suggest that the presence of health imagery on a food product's package can lead consumers to infer health benefits, even when other, more direct cues indicate that the product is unhealthy. This research informs debates on safeguarding consumers from potentially misleading health claims, through the regulation of imagery in food marketing.

Exposure to models' positive facial expressions whilst eating a raw vegetable increases children's acceptance and consumption of the modelled vegetable.

Research has shown that seeing positive facial expressions (FEs) towards food increased children's desire to eat foods rated as disliked. However, the effect of adults' positive FEs whilst eating a raw vegetable on children's acceptance and intake of nutritious foods that are less preferred (e.g., vegetables) remains to be established. This study aimed to examine the effect of models' FEs eating raw broccoli on children's acceptance and intake of raw broccoli. 111 children aged 4-6 years (64 male, 47 female) were randomised to watch a video of unfamiliar adult models eating raw broccoli with a positive or neutral facial expression (FE), or a non-food control video. Children's acceptance and intake of raw broccoli was assessed. Data about parent and child characteristics was provided by parents. There was a main effect of FE type on children's frequency of tastes (p = .03) and intake of broccoli (p = .02). Children who were exposed to models eating broccoli with positive FEs had greater frequency of tastes (p = .04) and intake of broccoli (p = .03), than children in the control condition, but not compared to children in the neutral FE condition (p > .05). There was no effect of positive FEs on children's willingness to try broccoli (p > .05). These findings suggest that observing others enjoy a commonly disliked vegetable can encourage children's tastes and intake of the vegetable. Thus, exposing children to others enjoying vegetables could be a useful strategy for encouraging healthier eating in children. Further work is needed to determine whether a single exposure is sufficient and whether these effects are sustained over time.

Expression and function of human ribonuclease 4 in the kidney and urinary tract.

Antimicrobial peptides are essential host defense mechanisms that prevent urinary tract infections. Recent studies have demonstrated that peptides in the ribonuclease A superfamily have antimicrobial activity against uropathogens and protect the urinary tract from uropathogenic Escherichia coli (UPEC). Little is known about the antibacterial function or expression of ribonuclease 4 (RNase 4) in the human urinary tract. Here, we show that full-length recombinant RNase 4 peptide and synthetic amino-terminal RNase 4 peptide fragment have antibacterial activity against UPEC and multidrug-resistant (MDR)-UPEC. RNASE4 transcript expression was detected in human kidney and bladder tissue using quantitative real-time PCR. Immunostaining or in situ hybridization localized RNase 4 expression to proximal tubules, principal and intercalated cells in the kidney's collecting duct, and the bladder urothelium. Urinary RNase 4 concentrations were quantified in healthy controls and females with a history of urinary tract infection. Compared with controls, urinary RNase 4 concentrations were significantly lower in females with a history of urinary tract infection. When RNase 4 was neutralized in human urine or silenced in vitro using siRNA, urinary UPEC replication or attachment to and invasion of urothelial and kidney medullary cells increased. These data show that RNase 4 has antibacterial activity against UPEC, is expressed in the human urinary tract, and can contribute to host defense against urinary tract infections.NEW & NOTEWORTHY Ribonuclease 4 (RNase 4) is a newly identified host defense peptide in the human kidney and bladder. RNase 4 kills uropathogenic Escherichia coli (UPEC) and multidrug-resistant UPEC. RNase 4 prevents invasive UPEC infection and suppressed RNase 4 expression may be a risk factor for more severe or recurrent urinary tract infection.

Harnessing the anti-cancer natural product nimbolide for targeted protein degradation.

Nimbolide, a terpenoid natural product derived from the Neem tree, impairs cancer pathogenicity; however, the direct targets and mechanisms by which nimbolide exerts its effects are poorly understood. Here, we used activity-based protein profiling (ABPP) chemoproteomic platforms to discover that nimbolide reacts with a novel functional cysteine crucial for substrate recognition in the E3 ubiquitin ligase RNF114. Nimbolide impairs breast cancer cell proliferation in-part by disrupting RNF114-substrate recognition, leading to inhibition of ubiquitination and degradation of tumor suppressors such as p21, resulting in their rapid stabilization. We further demonstrate that nimbolide can be harnessed to recruit RNF114 as an E3 ligase in targeted protein degradation applications and show that synthetically simpler scaffolds are also capable of accessing this unique reactive site. Our study highlights the use of ABPP platforms in uncovering unique druggable modalities accessed by natural products for cancer therapy and targeted protein degradation applications.

Discovery of a ZIP7 inhibitor from a Notch pathway screen.

The identification of activating mutations in NOTCH1 in 50% of T cell acute lymphoblastic leukemia has generated interest in elucidating how these mutations contribute to oncogenic transformation and in targeting the pathway. A phenotypic screen identified compounds that interfere with trafficking of Notch and induce apoptosis via an endoplasmic reticulum (ER) stress mechanism. Target identification approaches revealed a role for SLC39A7 (ZIP7), a zinc transport family member, in governing Notch trafficking and signaling. Generation and sequencing of a compound-resistant cell line identified a V430E mutation in ZIP7 that confers transferable resistance to the compound NVS-ZP7-4. NVS-ZP7-4 altered zinc in the ER, and an analog of the compound photoaffinity labeled ZIP7 in cells, suggesting a direct interaction between the compound and ZIP7. NVS-ZP7-4 is the first reported chemical tool to probe the impact of modulating ER zinc levels and investigate ZIP7 as a novel druggable node in the Notch pathway.

A pneumococcal pneumonia and influenza vaccination quality improvement program for women receiving chemotherapy for gynecologic cancers at a major tertiary cancer Centre.

OBJECTIVE: International guidelines recommend pneumococcal pneumonia and influenza vaccination for all patients with solid organ malignancies prior to initiating chemotherapy. Baseline vaccination rates (March 2019) for pneumococcal pneumonia and influenza at our tertiary cancer centre were 8% and 40%, respectively. The aim of this study was to increase the number of gynecologic chemotherapy patients receiving pneumococcal and influenza vaccinations to 80% by March 2020. METHODS: We performed an interrupted time series study using structured quality improvement methodology. Three interventions were introduced to address vaccination barriers: an in-house vaccination program, a staff education campaign, and a patient care bundle (pre-printed prescription, information brochure, vaccine record booklet). Process and outcome data were collected by patient survey and pharmacy audit and analyzed on statistical process control charts. RESULTS: We identified 195 eligible patients. Pneumococcal and influenza vaccination rates rose significantly from 5% to a monthly mean of 61% and from 36% to a monthly mean of 67%, respectively. The 80% target was reached for both vaccines during one or more months of study. The in-house vaccination and staff education programs were major contributors to the improvement, whereas the information brochure and record booklet were minor contributors. CONCLUSIONS: Three interventions to promote pneumococcal and influenza vaccination among chemotherapy patients resulted in significantly improved vaccination rates. Lessons learned about promoting vaccine uptake may be generalizable to different populations and vaccine types. In response to the global COVID-19 pandemic, initiatives to expand the program to all chemotherapy patients at our centre are underway.