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.

Can social media be used to increase fruit and vegetable consumption? A pilot intervention study.

Background: Exposure to social norms about fruit and vegetable intake has been shown to increase individuals' consumption of these foods. Further, exposure to socially endorsed 'healthy' food posts can increase consumption of low energy-dense (LED), relative to high energy-dense (HED) foods. The current pilot study aimed to investigate whether exposure to healthy eating (vs. control) social media accounts can shift normative perceptions about what others eat, eating intentions and self-reported food consumption. Methods: In a 2 (condition) × 2 (type of food consumed) mixed factorial design, 52 male and female students were asked to follow either healthy eating (intervention) or interior design (control) Instagram accounts over a two-week period. Baseline and post-intervention measures assessed normative perceptions of Instagram users' consumption of fruit and vegetables (LED foods), and energy dense snacks and sugar sweetened beverages (HED foods). Participants' intentions to consume, and self-reported consumption of these foods, were also measured. Results: There were no significant changes in perceptions about what others eat, or participants' own eating intentions (ps > 0.05). However, the intervention increased participants' self-reported consumption of LED foods by 1.37 servings (per day) and decreased consumption of HED foods by 0.81 items (per day), compared to the control condition (ps < 0.05). Conclusions: This novel pilot study demonstrates that a social norm-based social media intervention can successfully encourage healthier eating, with a large effect after two weeks. Certain social media platforms may therefore provide a viable tool for nudging healthy eating. Future work will aim to replicate these findings in a larger and more diverse sample.

Enhancing the Small-Scale Screenable Biological Space beyond Known Chemogenomics Libraries with Gray Chemical Matter─Compounds with Novel Mechanisms from High-Throughput Screening Profiles.

Phenotypic assays have become an established approach to drug discovery. Greater disease relevance is often achieved through cellular models with increased complexity and more detailed readouts, such as gene expression or advanced imaging. However, the intricate nature and cost of these assays impose limitations on their screening capacity, often restricting screens to well-characterized small compound sets such as chemogenomics libraries. Here, we outline a cheminformatics approach to identify a small set of compounds with likely novel mechanisms of action (MoAs), expanding the MoA search space for throughput limited phenotypic assays. Our approach is based on mining existing large-scale, phenotypic high-throughput screening (HTS) data. It enables the identification of chemotypes that exhibit selectivity across multiple cell-based assays, which are characterized by persistent and broad structure activity relationships (SAR). We validate the effectiveness of our approach in broad cellular profiling assays (Cell Painting, DRUG-seq, and Promotor Signature Profiling) and chemical proteomics experiments. These experiments revealed that the compounds behave similarly to known chemogenetic libraries, but with a notable bias toward novel protein targets. To foster collaboration and advance research in this area, we have curated a public set of such compounds based on the PubChem BioAssay dataset and made it available for use by the scientific community.

"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.

Repeated exposure to models' positive facial expressions whilst eating a raw vegetable increases children's consumption of the modelled vegetable.

Exposing children to adults eating a raw vegetable with positive facial expressions ('positive modelling') increases children's consumption of the modelled vegetable. However, whether repeated versus a single exposure to positive modelling enhances this effect, and whether it generalises to a non-modelled vegetable, remains to be examined. Hence, this study examined the effect of a single exposure, versus repeated, exposure to positive modelling on children's acceptance and intake of a modelled and non-modelled vegetable. Children aged 5-6 years (N = 153; 81 males, 72 females) were randomised to one of three conditions in which they had i) a single or ii) repeated exposure to a video of adults eating raw broccoli with positive facial expressions or iii) were exposed to a no-food control video. Children's acceptance (measured as willingness to try and number of tastes), intake and liking of a modelled (raw broccoli) and non-modelled vegetable (raw mangetout) were measured. Children had greater raw broccoli consumption and liking if they had received repeated exposure to positive modelling, compared to children who had received a single exposure, but not compared to children in the control condition. Children's mangetout intake was greater in the single (versus repeated) positive condition, but this effect was not dependent on time. There was no effect on children's vegetable acceptance. Repeatedly exposing children to adults enjoying a vegetable encourages children's intake of the modelled vegetable in comparison to a single exposure. Thus, repeated exposure to others' food enjoyment may be a practical and useful strategy to encourage children's vegetable consumption.

Impact of minimally invasive lung transplantation on early outcomes and analgesia use: A matched cohort study.

BACKGROUND: Minimally invasive (MI) approaches to lung transplantation (LTx) offer the prospect of faster recovery compared to traditional incisions, however, little data exist describing the impact of surgical technique on early outcomes and analgesia use. METHODS: A prospectively maintained institutional registry identified 170 patients who underwent LTx between January, 2017 and June, 2022. Post-COVID acute respiratory distress syndrome, repeat, and multiorgan transplants were excluded (n = 27) leaving 37 MILTx and 106 traditional LTx patients. Propensity score matching by age, sex, body mass index, diagnosis, lung allocation score, double vs. single lung, hypertension, diabetes, and hospitalization status created 37 pairs. RESULTS: Before matching, MILTx patients were more often male (70% vs 43%) and more likely to receive grafts from younger (31 vs 42 years), circulatory death donors (19% vs 6%) compared with traditional LTx patients (all p < 0.05). After matching, there were no differences in graft warm ischemia or operative duration (both p > 0.05). Postoperatively, MILTx experienced shorter intensive care unit (ICU) (4.3 [IQR 3.1-5.5] vs 8.2 [IQR 3.7-10.8] days) and hospital lengths of stay (LOS) (13 [IQR 11-15] vs 17 [IQR 12-25] days) (both p < 0.05). Among patients surviving to discharge, MILTx patients required fewer opioid prescriptions at discharge (38% vs 66%, p = 0.008) and had improved pulmonary function at 3 months (Forced expiratory volume in 1 second 82 [IQR 72-102] vs 77 [IQR 52-88]% predicted; forced vital capacity 78 [IQR 65-92] vs 70 [IQR 62-80]% predicted] (both p < 0.05). CONCLUSION: Minimally invasive LTx techniques demonstrate potential advantages over traditional approaches, including reduced ICU and hospital LOS, lower opioid use on discharge, and improved early pulmonary function.

DCAF1-based PROTACs with activity against clinically validated targets overcoming intrinsic- and acquired-degrader resistance.

Targeted protein degradation (TPD) mediates protein level through small molecule induced redirection of E3 ligases to ubiquitinate neo-substrates and mark them for proteasomal degradation. TPD has recently emerged as a key modality in drug discovery. So far only a few ligases have been utilized for TPD. Interestingly, the workhorse ligase CRBN has been observed to be downregulated in settings of resistance to immunomodulatory inhibitory drugs (IMiDs). Here we show that the essential E3 ligase receptor DCAF1 can be harnessed for TPD utilizing a selective, non-covalent DCAF1 binder. We confirm that this binder can be functionalized into an efficient DCAF1-BRD9 PROTAC. Chemical and genetic rescue experiments validate specific degradation via the CRL4DCAF1 E3 ligase. Additionally, a dasatinib-based DCAF1 PROTAC successfully degrades cytosolic and membrane-bound tyrosine kinases. A potent and selective DCAF1-BTK-PROTAC (DBt-10) degrades BTK in cells with acquired resistance to CRBN-BTK-PROTACs while the DCAF1-BRD9 PROTAC (DBr-1) provides an alternative strategy to tackle intrinsic resistance to VHL-degrader, highlighting DCAF1-PROTACS as a promising strategy to overcome ligase mediated resistance in clinical settings.

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.

Limited cumulative experience with ex vivo lung perfusion is associated with inferior outcomes after lung transplantation.

OBJECTIVE: Ex vivo lung perfusion (EVLP) allows for prolonged preservation and evaluation/resuscitation of donor lungs. We evaluated the influence of center experience with EVLP on lung transplant outcomes. METHODS: We identified 9708 isolated, first-time adult lung transplants from the United Network for Organ Sharing database (March 1, 2018-March 1, 2022), 553 (5.7%) involved using donor lungs after EVLP. Using the total volume of EVLP lung transplants per center during the study period, centers were dichotomized into low- (1-15 cases) and high-volume (>15 cases) EVLP centers. RESULTS: Forty-one centers performed EVLP lung transplants, including 26 low-volume and 15 high-volume centers (median volume, 3 vs 23 cases; P < .001). Recipients at low-volume centers (n = 109) had similar baseline comorbidities compared with high-volume centers (n = 444). Low-volume centers used numerically more donation after circulatory death donors (37.6 vs 28.4%; P = .06) and more donors with Pao2/Fio2 ratio <300 (24.8 vs 9.7%; P < .001). After EVLP lung transplants, low-volume centers had worse 1-year survival (77.8% vs 87.5%; P = .007), with an adjusted hazard ratio of 1.63 (95% CI, 1.06-2.50, adjusting for recipient age, sex, diagnosis, lung allocation score, donation after circulatory death donor, donor Pao2/Fio2 ratio, and total annual lung transplant volume per center). When compared to non-EVLP lung transplants, 1-year survival of EVLP lung transplants was significantly worse at low-volume centers (adjusted hazard ratio, 2.09; 95% CI, 1.47-2.97) but similar at high-volume centers (adjusted hazard ratio, 1.14; 95% CI, 0.82-1.58). CONCLUSIONS: The use of EVLP in lung transplantation remains limited. Increasing cumulative EVLP experience is associated with improved outcomes of lung transplantation using EVLP-perfused allografts.

Agreement between cause of death assignment by computer-coded verbal autopsy methods and physician coding of verbal autopsy interviews in South Africa.

BACKGROUND: The South African national cause of death validation (NCODV 2017/18) project collected a national sample of verbal autopsies (VA) with cause of death (COD) assignment by physician-coded VA (PCVA) and computer-coded VA (CCVA). OBJECTIVE: The performance of three CCVA algorithms (InterVA-5, InSilicoVA and Tariff 2.0) in assigning a COD was compared with PCVA (reference standard). METHODS: Seven performance metrics assessed individual and population level agreement of COD assignment by age, sex and place of death subgroups. Positive predictive value (PPV), sensitivity, overall agreement, kappa, and chance corrected concordance (CCC) assessed individual level agreement. Cause-specific mortality fraction (CSMF) accuracy and Spearman's rank correlation assessed population level agreement. RESULTS: A total of 5386 VA records were analysed. PCVA and CCVAs all identified HIV/AIDS as the leading COD. CCVA PPV and sensitivity, based on confidence intervals, were comparable except for HIV/AIDS, TB, maternal, diabetes mellitus, other cancers, and some injuries. CCVAs performed well for identifying perinatal deaths, road traffic accidents, suicide and homicide but poorly for pneumonia, other infectious diseases and renal failure. Overall agreement between CCVAs and PCVA for the top single cause (48.2-51.6) indicated comparable weak agreement between methods. Overall agreement, for the top three causes showed moderate agreement for InterVA (70.9) and InSilicoVA (73.8). Agreement based on kappa (-0.05-0.49)and CCC (0.06-0.43) was weak to none for all algorithms and groups. CCVAs had moderate to strong agreement for CSMF accuracy, with InterVA-5 highest for neonates (0.90), Tariff 2.0 highest for adults (0.89) and males (0.84), and InSilicoVA highest for females (0.88), elders (0.83) and out-of-facility deaths (0.85). Rank correlation indicated moderate agreement for adults (0.75-0.79). CONCLUSIONS: Whilst CCVAs identified HIV/AIDS as the leading COD, consistent with PCVA, there is scope for improving the algorithms for use in South Africa.

Preserved 2-y Liver Transplant Outcomes Following Simultaneous Thoracoabdominal DCD Organ Procurement Despite Effects on Liver Utilization Rate.

Background: Current techniques for donation after circulatory determination of death (DCD) heart procurement, through either direct procurement and machine perfusion or thoracoabdominal normothermic regional perfusion (NRP), have demonstrated excellent heart transplant outcomes. However, the impact of thoracoabdominal DCD (TA-DCD) heart procurement on liver allograft outcomes and utilization is poorly understood. Methods: One hundred sixty simultaneous heart and liver DCD donors were identified using the United Network for Organ Sharing/Organ Procurement and Transplantation Network database between December 2019 and July 2021. Liver outcomes from TA-DCD donors were stratified by heart procurement technique and evaluated for organ utilization, graft survival, and patient survival. Results were compared with abdominal-only DCD (A-DCD; n = 1332) and donation after brain death (DBD; n = 12 891) liver transplants during the study interval. Kaplan-Meier methods with log-rank testing were used to evaluate patient and graft survival. Results: One hundred thirty-three of 160 livers procured from TA-DCD donors proceeded to transplant. TA-DCD donors were younger (mean 28.26 y; P < 0.0001) with lower body mass index (mean 26.61; P < 0.0001) than A-DCD and DBD donors. TA-DCD livers had equivalent patient survival ( P = 0.893) and superior graft survival (P = 0.009) compared with A-DCD. TA-DCD livers had higher rates of organ discard for long warm ischemia time (37.0%) than A-DCD (20.5%) and DBD (0.5%; P < 0.0001), with direct procurement and machine perfusion procurements leading to a higher discard rate (18.5%) than NRP procurements (7.4%). Conclusions: Liver transplants after TA-DCD donation demonstrated equivalent patient outcomes and excellent graft outcomes. NRP procurements resulted in the lowest rate of organ discard after DCD donation and may represent an optimal strategy to maximize organ utilization.

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.

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.

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.

The Effects of an Acute Bout of Aerobic or Resistance Exercise on Nonexercise Physical Activity.

Introduction/Purpose: A reduction in nonexercise physical activity (NEPA) after exercise may reduce the effectiveness of exercise interventions on weight loss in adults with overweight or obesity. Aerobic exercise (AEx) and resistance exercise (REx) may have different effects on NEPA. The purpose of this secondary analysis was to examine the effect of a single bout of AEx or REx on NEPA and sedentary behavior in inactive adults with overweight or obesity. Methods: Adults with overweight or obesity (n = 24; 50% male; age, 34.5 ± 1.5 yr; body mass index, 28.5 ± 0.9 kg·m-2) not meeting current physical activity guidelines completed a single 45-min bout of AEx, REx, or a sedentary control on different days in random order. After each condition, participants' NEPA was recorded for 84 h by accelerometer. Time spent sedentary and in light, moderate, and vigorous physical activity; steps; metabolic equivalent of task (MET)-hours; and sit-to-stand transitions were calculated using activity count data. Results: No differences were observed in the percent of waking time spent sedentary and in light, moderate, and vigorous activity between conditions (P > 0.05). No differences were observed in steps, MET-hours, or sit-to-stand transitions between conditions (P > 0.05). NEPA responses were variable among individuals, with approximately half of participants reducing and half increasing NEPA over the 84 h after each exercise condition. Conclusion: NEPA was not reduced after an acute bout of AEx or REx in a sample of inactive adults with overweight or obesity.

The effect of warm ischemia and donor ejection fraction on 30-day mortality after donation after circulatory death heart transplantation: A national database analysis.

Donation after circulatory death (DCD) donor hearts recovered using the direct procurement and perfusion method experience variable durations of warm ischemia at the time of procurement (WIP). We used the Organ Procurement and Transplantation Network database to assess the effect of WIP on 30-day mortality after DCD heart transplantation. The analysis evaluated outcomes in 237 recipients of DCD heart transplantation, demonstrating an optimal WIP cut point of <36 minutes. Multivariable logistic regression modeling identified donor left ventricular ejection fraction (LVEF) <60% as an independent predictor of 30-day mortality. The area under the receiver operating characteristic curve for predicting 30-day mortality based on WIP ≥36 minutes and donor LVEF <60% was 0.90. Based on these findings, we do not recommend proceeding with DCD heart transplantation for patients with WIP ≥36 minutes, particularly in donors with LVEF <60%.

Simultaneous Lung-Kidney Transplantation in the United States.

BACKGROUND: Simultaneous lung-kidney transplantation is rarely performed. Contemporary national practice trends and outcomes are unclear. METHODS: From the United Network for Organ Sharing database, we identified 108 lung-kidney transplant recipients (2005-2022). They were compared with isolated lung recipients with pretransplantation dialysis or estimated glomerular filtration rate (eGFR) ≤30 mL/min per 1.73 m2 (n = 372) and isolated non-dialysis-dependent lung recipients with 30 < eGFR < 50 mL/min per 1.73 m2 (n = 1416), respectively. Lung-kidney recipients were also compared with recipients of the contralateral kidney from the same donors (n = 90). RESULTS: Lung-kidney transplantation was performed by 36 centers, with increasing annual volume (1 in 2005, 16 in 2022; P < .01). Forty percent (44/108) of lung-kidney recipients received pretransplantation dialysis, and of those without pretransplantation dialysis, median eGFR was 30.7 mL/min per 1.73 m2. Lung-kidney recipients had improved survival compared with isolated lung recipients with eGFR ≤30 mL/min per 1.73 m2 or pretransplantation dialysis (adjusted hazard ratio, 0.59; 95% CI, 0.38-0.92). However, no survival benefit was observed when lung-kidney recipients were compared with isolated lung recipients with 30 < eGFR < 50 mL/min per 1.73 m2 and no pretransplantation dialysis (adjusted hazard ratio, 0.88; 95% CI, 0.55-1.41). Compared with isolated kidney recipients using the contralateral kidney from the same donors, lung-kidney recipients had a higher risk of kidney allograft loss (adjusted hazard ratio, 3.27; 95% CI, 1.22-8.78), a difference largely accounted for by patient death with a functioning kidney allograft. CONCLUSIONS: Recipients of lung-kidney transplants had improved survival compared with isolated lung recipients with eGFR ≤30 mL/min per 1.73 m2 or pretransplantation dialysis. However, lung-kidney recipients had a higher rate of kidney allograft loss than recipients of the contralateral kidney allograft from the same donors.

The impact of thoracoabdominal normothermic regional perfusion on early outcomes in donation after circulatory death lung transplantation.

Thoracoabdominal normothermic regional perfusion has emerged as an alternative method to procure donation after circulatory death (DCD) hearts, but its impact on concomitantly procured lung allografts remains unclear. The United Network for Organ Sharing database identified 627 DCD donors whose hearts were procured (211 in situ perfused, 416 directly procured) between December 2019 to December 2022. Lung utilization rates were 14.9% (63/422) for in situ perfused donors and 13.8% (115/832) for directly procured donors (p = 0.80). Following transplantation, lung recipients from in situ perfused donors required numerically lower rates of extracorporeal membrane oxygenation (7.7% vs 17.0%, p = 0.26) and mechanical ventilation (34.6% vs 47.2%, p = 0.29) at 72 hours. Six-month post-transplant survival was similar between groups (85.7% vs 89.1%, p = 0.67). These results suggest that the use of thoracoabdominal normothermic regional perfusion in DCD heart procurement may not adversely impact recipients of concomitantly procured lung allografts.

Donation after circulatory death heart procurement strategy impacts utilization and outcomes of concurrently procured abdominal organs.

INTRODUCTION: The impact of donation after circulatory death (DCD) heart procurement techniques on the utilization and outcomes of concurrently procured DCD livers and kidneys remains unclear. METHODS: Using the United Network for Organ Sharing database, we identified 246 DCD donors whose heart was procured using direct procurement and ex-situ machine perfusion and 128 DCD donors whose heart was procured using in-situ thoracoabdominal normothermic regional perfusion (12/2019-03/2022). We evaluated the transplantation rate of concurrently procured DCD livers and kidneys (defined as the number of organs transplanted/total number of organs available for procurement) and their post-transplant outcomes. RESULTS: The transplantation rate of concurrently procured DCD livers was higher with in-situ perfusion compared to direct procurement (67.1% vs 56.5%, p = 0.045). After excluding pediatric, multiorgan, and repeat transplant recipients, there was no difference in 6-month liver graft failure rate (direct procurement 0.9% vs in-situ perfusion 0%, p > 0.99). Recipients of kidneys procured with in-situ perfusion had less delayed graft function (11.3% vs 41.5%, p < 0.0001) shorter length of stay, and lower serum creatinine at discharge (both p < 0.05). Six-month recipient survival in the direct procurement and in-situ perfusion group were similar after DCD liver and kidney transplantation (p = 0.24 and 0.79 respectively). CONCLUSIONS: Compared to direct procurement, DCD heart procurement with in-situ thoracoabdominal normothermic regional perfusion was associated with increased utilization of DCD livers and a lower incidence of delayed graft function in concurrently procured DCD kidneys. Broader implementation of DCD heart transplantation must maximize the transplant potential of concurrently procured abdominal organs and ensure their successful outcomes.