Pragmatic Trial of Hospitalization Rate in Chronic Kidney Disease.

BACKGROUND: Despite the availability of effective therapies for patients with chronic kidney disease, type 2 diabetes, and hypertension (the kidney-dysfunction triad), the results of large-scale trials examining the implementation of guideline-directed therapy to reduce the risk of death and complications in this population are lacking. METHODS: In this open-label, cluster-randomized trial, we assigned 11,182 patients with the kidney-dysfunction triad who were being treated at 141 primary care clinics either to receive an intervention that used a personalized algorithm (based on the patient's electronic health record [EHR]) to identify patients and practice facilitators to assist providers in delivering guideline-based interventions or to receive usual care. The primary outcome was hospitalization for any cause at 1 year. Secondary outcomes included emergency department visits, readmissions, cardiovascular events, dialysis, and death. RESULTS: We assigned 71 practices (enrolling 5690 patients) to the intervention group and 70 practices (enrolling 5492 patients) to the usual-care group. The hospitalization rate at 1 year was 20.7% (95% confidence interval [CI], 19.7 to 21.8) in the intervention group and 21.1% (95% CI, 20.1 to 22.2) in the usual-care group (between-group difference, 0.4 percentage points; P = 0.58). The risks of emergency department visits, readmissions, cardiovascular events, dialysis, or death from any cause were similar in the two groups. The risk of adverse events was also similar in the trial groups, except for acute kidney injury, which was observed in more patients in the intervention group (12.7% vs. 11.3%). CONCLUSIONS: In this pragmatic trial involving patients with the triad of chronic kidney disease, type 2 diabetes, and hypertension, the use of an EHR-based algorithm and practice facilitators embedded in primary care clinics did not translate into reduced hospitalization at 1 year. (Funded by the National Institutes of Health and others; ICD-Pieces ClinicalTrials.gov number, NCT02587936.).

Quantum coherent energy transport in the Fenna-Matthews-Olson complex at low temperature.

In the primary step of natural light harvesting, the solar photon energy is captured in a photoexcited electron-hole pair, or an exciton, in chlorophyll. Its conversion to chemical potential occurs in the special pair reaction center, which is reached by downhill ultrafast excited-state energy transport through a network of chromophores. Being inherently quantum, transport could in principle occur via a matter wave, with vast implications for efficiency. How long a matter wave remains coherent is determined by the intensity by which the exciton is disturbed by the noisy biological environment. The stronger this is, the stronger the electronic coupling between chromophores must be to overcome the fluctuations and phase shifts. The current consensus is that under physiological conditions, quantum coherence vanishes on the 10-fs time scale, rendering it irrelevant for the observed picosecond transfer. Yet, at low-enough temperature, quantum coherence should in principle be present. Here, we reveal the onset of longer-lived electronic coherence at extremely low temperatures of ∼20 K. Using two-dimensional electronic spectroscopy, we determine the exciton coherence times in the Fenna-Matthew-Olson complex over an extensive temperature range. At 20 K, coherence persists out to 200 fs (close to the antenna) and marginally up to 500 fs at the reaction center. It decays markedly faster with modest increases in temperature to become irrelevant above 150 K. At low temperature, the fragile electronic coherence can be separated from the robust vibrational coherence, using a rigorous theoretical analysis. We believe that by this generic principle, light harvesting becomes robust against otherwise fragile quantum effects.

Deep generative priors for biomolecular 3D heterogeneous reconstruction from cryo-EM projections.

Cryo-electron microscopy has become a powerful tool to determine three-dimensional (3D) structures of rigid biological macromolecules from noisy micrographs with single-particle reconstruction. Recently, deep neural networks, e.g., CryoDRGN, have demonstrated conformational and compositional heterogeneity of complexes. However, the lack of ground-truth conformations poses a challenge to assess the performance of heterogeneity analysis methods. In this work, variational autoencoders (VAE) with three types of deep generative priors were learned for latent variable inference and heterogeneous 3D reconstruction via Bayesian inference. More specifically, VAEs with "Variational Mixture of Posteriors" priors (VampPrior-SPR), non-parametric exemplar-based priors (ExemplarPrior-SPR) and priors from latent score-based generative models (LSGM-SPR) were quantitatively compared with CryoDRGN. We built four simulated datasets composed of hypothetical continuous conformation or discrete states of the hERG K + channel. Empirical and quantitative comparisons of inferred latent representations were performed with affine-transformation-based metrics. These models with more informative priors gave better regularized, interpretable factorized latent representations with better conserved pairwise distances, less deformed latent distributions and lower within-cluster variances. They were also tested on experimental datasets to resolve compositional and conformational heterogeneity (50S ribosome assembly, cowpea chlorotic mottle virus, and pre-catalytic spliceosome) with comparable high resolution. Codes and data are available: https://github.com/benjamin3344/DGP-SPR.

Limitations of antifungal prophylaxis in preventing invasive Candida surgical site infections after liver transplant surgery.

Invasive primary Candida surgical site infections (IP-SSIs) are a common complication of liver transplantation, and targeted antifungal prophylaxis is an efficient strategy to limit their occurrence. We performed a retrospective single-center cohort study among adult single liver transplant recipients at Duke University Hospital in the period between 1 January 2015 and 31 December 2020. The study aimed to determine the rate of Candida IP-SSI according to the peri-transplant antifungal prophylaxis received. Of 470 adult single liver transplant recipients, 53 (11.3%) received micafungin prophylaxis, 100 (21.3%) received fluconazole prophylaxis, and 317 (67.4%) did not receive systemic antifungal prophylaxis in the peri-transplant period. Ten Candida IP-SSIs occurred among 5 of 53 (9.4%) micafungin recipients, 1 of 100 (1.0%) fluconazole recipients, and 4 of 317 (1.3%) recipients who did not receive antifungal prophylaxis. Our study highlights the limitations of antifungal prophylaxis in preventing invasive Candida IP-SSI after liver transplant surgery. We hypothesize that pathogen, host, and pharmacokinetic-related factors contributed to the occurrence of Candida IP-SSI despite antifungal prophylaxis. Our study reinforces the need for a risk-based, multi-pronged approach to fungal prevention, including targeted antifungal administration in patients with risks for invasive candidiasis and close monitoring, especially among patients with surgically complex procedures, with timely control of surgical leaks.

Recommendations for the use of next-generation sequencing (NGS) for patients with advanced cancer in 2024: a report from the ESMO Precision Medicine Working Group.

BACKGROUND: Advancements in the field of precision medicine have prompted the European Society for Medical Oncology (ESMO) Precision Medicine Working Group to update the recommendations for the use of tumour next-generation sequencing (NGS) for patients with advanced cancers in routine practice. METHODS: The group discussed the clinical impact of tumour NGS in guiding treatment decision using the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) considering cost-effectiveness and accessibility. RESULTS: As for 2020 recommendations, ESMO recommends running tumour NGS in advanced non-squamous non-small-cell lung cancer, prostate cancer, colorectal cancer, cholangiocarcinoma, and ovarian cancer. Moreover, it is recommended to carry out tumour NGS in clinical research centres and under specific circumstances discussed with patients. In this updated report, the consensus within the group has led to an expansion of the recommendations to encompass patients with advanced breast cancer and rare tumours such as gastrointestinal stromal tumours, sarcoma, thyroid cancer, and cancer of unknown primary. Finally, ESMO recommends carrying out tumour NGS to detect tumour-agnostic alterations in patients with metastatic cancers where access to matched therapies is available. CONCLUSION: Tumour NGS is increasingly expanding its scope and application within oncology with the aim of enhancing the efficacy of precision medicine for patients with cancer.

Impact of chronic kidney disease and end-stage renal disease on outcomes after complex endovascular and open aortic aneurysm repair.

OBJECTIVE: Chronic kidney disease (CKD) and end-stage renal disease are traditionally associated with worse outcomes after endovascular aortic repair (EVAR) and open aneurysm repair (OAR) of abdominal aortic aneurysms (AAAs). However, there needs to be more data on complex AAA repair involving the aorta's visceral segment. This study stratifies complex AAA repair outcomes by CKD severity and dialysis dependence. METHODS: All patients undergoing elective OAR and fenestrated/branched EVAR (F-BEVAR) for complex AAA with preoperative renal function data captured by the Vascular Quality Initiative between January 2003 and September 2020 were analyzed. Patients were stratified by CKD class as follows: normal/mild (CKD 1 and 2), moderate (CKD class 3a), moderate to severe (CKD 3b), severe (CKD class 4 and 5), and dialysis. Only patients with clamp sites above one of the renal arteries were included for complex OAR. For F-BEVAR, patients with proximal landing zones below zone 5 (above celiac artery) were included, and distal landing zones between zones 1 and 5 were excluded. Primary outcomes were perioperative and 1-year mortality. Predictors of mortality were identified by Cox multivariate regression models. RESULTS: We identified 7849 elective complex AAA repairs: 4230 (54%) complex OARs and 3619 (46%) F-BEVARs. Most patients were White (89%) and male (74%), with an average age of 72 ± 8 years. The patients who underwent F-BEVAR were older and had more comorbidities. Elective F-BEVAR for complex AAA started in 2012 and increased from 1.4% in 2012 to 58% in 2020 (P < .001). The OAR cohort had more perioperative complications, but less 1-year mortality. The normal/mild CKD cohort had the highest 1-year survival compared with other groups after both complex OAR and F-BEVAR. On Cox regression analysis, when compared with CKD 1-2, worsening CKD stage (CKD 3b: hazard ratio [HR], 2.5; 95% confidence interval [CI], 1.82-3.40; P < .001; CKD 4-5: HR, 1.9; 95% CI, 1.16-3.26; P = .011; and dialysis: HR, 4.4; 95% CI, 2.53-7.72; P < .001) were independently associated with 1-year survival after F-BEVAR. After complex OAR, worsening CKD stage but not dialysis was associated with 1-year mortality compared with CKD 1-2 (CKD 3b: HR, 1.6; 95% CI, 1.13-2.35; P = .009; CKD 4-5: HR, 3.4; 95% CI, 2.03-5.79; P < .001). CONCLUSIONS: CKD severity is an essential predictor of perioperative and 1-year mortality after complex AAA repair, irrespective of the treatment modality, which may reflect the natural history of CKD. Consideration should be given to raising the threshold for elective AAA repair in patients with moderate to severe CKD and end-stage renal disease, given the high 1-year mortality rate.

Evaluating the influence of marine protected areas on surf zone fish.

Marine protected areas (MPAs) globally serve conservation and fisheries management goals, generating positive effects in some marine ecosystems. Surf zones and sandy beaches, critical ecotones bridging land and sea, play a pivotal role in the life cycles of numerous fish species and serve as prime areas for subsistence and recreational fishing. Despite their significance, these areas remain understudied when evaluating the effects of MPAs. We compared surf zone fish assemblages inside and outside MPAs across 3 bioregions in California (USA). Using seines and baited remote underwater videos (BRUVs), we found differences in surf zone fish inside and outside MPAs in one region. Inside south region MPAs, we observed higher abundance (Tukey's honest significant difference [HSD] = 0.83, p = 0.0001) and richness (HSD = 0.22, p = 0.0001) in BRUVs and greater biomass (HSD = 0.32, p = 0.0002) in seine surveys compared with reference sites. Selected live-bearing, fished taxa were positively affected by MPAs. Elasmobranchs displayed greater abundance in BRUV surveys and higher biomass in seine surveys inside south region MPAs (HSD = 0.35, p = 0.0003 and HSD = 0.23, p = 0.008, respectively). Although we observed no overall MPA signal for Embiotocidae, abundances of juvenile and large adult barred surfperch (Amphistichus argenteus), the most abundant fished species, were higher inside MPAs (K-S test D = 0.19, p < 0.0001). Influence of habitat characteristics on MPA performance indicated surf zone width was positively associated with fish abundance and biomass but negatively associated with richness. The south region had the largest positive effect size on all MPA performance metrics. Our findings underscored the variability in species richness and composition across regions and survey methods that significantly affected differences observed inside and outside MPAs. A comprehensive assessment of MPA performance should consider specific taxa, their distribution, and the effects of habitat factors and geography.

Evaluación de la influencia de las áreas marinas protegidas sobre los peces de la zona de rompientes Resumen Las áreas marinas protegidas (AMP) cumplen los objetivos de conservación y manejo de pesquerías a nivel mundial, lo que genera efectos positivos en algunos ecosistemas marinos. Las zonas de rompientes y las playas arenosas, ecotonos importantes que conectan la tierra con el mar, tienen un papel esencial en el ciclo de vida de varios peces y fungen como áreas óptimas para la pesca recreativa y de sustento. A pesar de su importancia, estas áreas están poco estudiadas con respecto a la evaluación del efecto de las AMP. Comparamos la composición de peces del área de rompientes dentro y fuera de las AMP de tres bioregiones de California, EUA. Usamos chinchorros y videos submarinos con carnada (BRUVs) y descubrimos diferencias en los peces de la zona de rompientes dentro y fuera de las AMP en una región. Dentro de las AMP de la región sur observamos una mayor abundancia (diferencia significativa honesta de Tukey [DSH]  =  0.83, p = 0.0001) y riqueza (DSH  =  0.22, p = 0.0001) en los BRUV y una mayor biomasa (DSH  =  0.32, p = 0.0002) en los censos con chinchorro en comparación con los sitios de referencia. Los taxones seleccionados de peces de sustento fueron afectados de manera positiva por las AMP. Los elasmobranquios mostraron una mayor abundancia en los BRUV y una mayor biomasa en los censos con chinchorro dentro de las AMP de la región sur (DSH  =  0.35, p = 0.0003 y DSH  =  0.23, p = 0.008, respectivamente). Aunque no observamos una señal generalizada de las AMP para la familia Embiotocidae, la abundancia de Amphistichus argenteus juveniles y adultos, la especie pescada más abundante, fue mayor dentro de las AMP (prueba K­S D  =  0.19, p < 0.0001). La influencia de las características del hábitat sobre el desempeño de las AMP indicó que el ancho de la zona de rompientes está asociado de forma positiva con la abundancia y biomasa de los peces, pero de forma negativa con la riqueza. La región sur tuvo el mayor tamaño de efecto positivo sobre todas las medidas de desempeño de las AMP. Nuestros hallazgos destacan la variabilidad en la riqueza y composición de especies en todas las regiones y los censos que afectan significativamente las diferencias observadas dentro y fuera de las AMP. Una evaluación completa del desempeño de las AMP debe considerar taxones específicos, su distribución y el efecto de los factores de hábitat y la geografía.

Short term air pollution exposure during pregnancy and associations with maternal immune markers.

BACKGROUND: Air pollution exposure during pregnancy has been associated with numerous adverse pregnancy, birth, and child health outcomes. One proposed mechanism underlying these associations is maternal immune activation and dysregulation. We examined associations between PM2.5 and NO2 exposure during pregnancy and immune markers within immune function groups (TH1, TH2, TH17, Innate/Early Activation, Regulatory, Homeostatic, and Proinflammatory), and examined whether those associations changed across pregnancy. METHODS: In a pregnancy cohort study (n=290) in Rochester, New York, we measured immune markers (using Luminex) in maternal plasma up to 3 times during pregnancy. We estimated ambient PM2.5 and NO2 concentrations at participants' home addresses using a spatial-temporal model. Using mixed effects models, we estimated changes in immune marker concentrations associated with interquartile range increases in PM2.5 (2.88 µg/m3) and NO2 (7.82 ppb) 0 to 6 days before blood collection, and assessed whether associations were different in early, mid, and late pregnancy. RESULTS: Increased NO2 concentrations were associated with higher maternal immune markers, with associations observed across TH1, TH2, TH17, Regulatory, and Homeostatic groups of immune markers. Furthermore, the largest increases in immune markers associated with each 7.82 ppb increase in NO2 concentration were in late pregnancy (e.g., IL-23 = 0.26 pg/ml, 95% CI= 0.07, 0.46) compared to early pregnancy (e.g., IL-23 = 0.08 pg/ml, 95% CI= -0.11, 0.26). CONCLUSIONS: Results were suggestive of NO2-related immune activation. Increases in effect sizes from early to mid to late pregnancy may be due to changes in immune function over the course of pregnancy. These findings provide a basis for immune activation as a mechanism for previously observed associations between air pollution exposure during pregnancy and reduced birthweight, fetal growth restriction, and pregnancy complications.

Quantum tomography of molecules using ultrafast electron diffraction.

We propose a quantum tomography (QT) approach to retrieve the temporally evolving reduced density matrix in electronic state basis, where the populations and coherence between the ground state and excited state are reconstructed from the ultrafast electron diffraction signal. In order to showcase the capability of the proposed QT approach, we simulate the nuclear wavepacket dynamics and ultrafast electron diffraction of photoexcited pyrrole molecules using the ab initio quantum chemical CASSCF method. From the simulated time-resolved diffraction data, we retrieve the evolving density matrix in a crude diabatic representation basis and reveal the symmetry of the excited pyrrole wavepacket. Our QT approach opens the route to make a quantum version of "molecular movie" that covers the electronic degree of freedom and equips ultrafast electron diffraction with the power to reveal the coherence between electronic states, relaxation, and dynamics of population transfer.

Management of acute cervical spinal cord injury in the non-specialist intensive care unit: a narrative review of current evidence.

Each year approximately one million people suffer spinal cord injury, which has significant physical, psychosocial and economic impacts on patients and their families. Spinal cord rehabilitation centres are a well-established part of the care pathway for patients with spinal cord injury and facilitate improvements in functional independence and reductions in healthcare costs. Within the UK, however, there are a limited number of spinal cord injury centres, which delays admission. Patients and their families often perceive that they are not receiving specialist care while being treated in non-specialist units. This review aimed to provide clinicians who work in non-specialist spinal injury centres with a summary of contemporary studies relevant to the critical care management of patients with cervical spinal cord injury. We undertook a targeted literature review including guidelines, systematic reviews, meta-analyses, clinical trials and randomised controlled trials published in English between 1 June 2017 and 1 June 2023. Studies involving key clinical management strategies published before this time, but which have not been updated or repeated, were also included. We then summarised the key management themes: acute critical care management approaches (including ventilation strategies, blood pressure management and tracheostomy insertion); respiratory weaning techniques; management of pain and autonomic dysreflexia; and rehabilitation.

"They Protect us as if they were our Mom" Masking Attitudes from Freelist Survey Data and Qualitative Interviews in San Diego School Communities.

BACKGROUND: Despite being disproportionately impacted by COVID-19 due to a lack of structural support, marginalized communities have been largely ignored in the politically polarized debate over school masking. In response to this, we sought to explore masking attitudes by centering the voices of parents and children at historically marginalized, predominantly Hispanic schools in southern California. METHODS: We conducted a mixed-methods study with parents and children attending 26 low-income predominantly Hispanic-serving elementary schools. A random sample of parents was asked to provide a freelist of words they associate with masking. A subset of parents with children aged 4-6 was recruited from these surveys to participate in parent-child interviews (PCI). We calculated Smith's salience index for all unique items, stratifying by language (English/Spanish). Item salience guided PCI thematic analysis for additional context and meaning. RESULTS: 648 participants provided 1118 unique freelist items in English and Spanish. 19 parent-child pairs were interviewed, 11 in Spanish and 8 in English. The most salient words were "safety"(0.37), "protection"(0.12), "prevention"(0.05), "health"(0.04), "good"(0.03), "can't breathe"(0.03), "necessary"(0.02), "care"(0.02), "precaution"(0.02), and "unnecessary"(0.02). Spanish speakers had a more favorable view of masking than English speakers, particularly regarding "protection" (0.20 vs 0.08) and "prevention" (0.10 vs 0.02). DISCUSSION: Masking is an affordable individual-level risk mitigation that protects the communities that have inequitably shouldered the burdens of the COVID-19 pandemic. We recommend that policymakers prioritize the views of those most impacted when deciding on risk mitigation policies like school masking.

Strength of relationship between body mass index and gross motor capacity in youth with intellectual disabilities.

BACKGROUND: Adequate skill levels of gross motor capacity affect activities of daily living, participation in recreational activities and general physical activity levels of youths (7-21 years). Most studies of typically developing youths have reported significant negative relationships between gross motor capacity and body mass index. The latter findings are especially of concern for youths with intellectual disabilities in that it has been estimated that 61% of children and 66% of adolescents were classified as overweight/obese. Therefore, the purpose of this study was to determine the strength of the relationship between body mass index and gross motor capacity among youths with mild to moderate intellectual disability (ID). METHODS: Components of the Bruininks-Oseretsky Test of Motor Proficiency (BOT-2) were used for designated aspects of gross motor capacity: six items for upper limb coordination (ULC); seven items for balance (BAL); six items for bilateral coordination (BLC); and one item for agility (A-2). Participants consisted of 654 youths (438 men), ages 8-21 years with ID. Participants were divided into pre-puberty and post-puberty men (post ≥12 years) and women (post ≥10 years of age). Body mass index (BMI, kg/m2) was determined by height and weight measurements on the day of testing. A Kendall's tau correlation coefficient (τ) was used to determine the strength of the relationship between body mass index and gross motor capacity (BOT-2 test scores). RESULTS: The τ values for both pre-puberty and post-puberty for all BAL, BLC, A-2 tests and for three of the six ULC tests were negligible to very weak (τ = 0 to ±0.19). Higher τ values were seen for pre-puberty youths in three of the ULC tests, but they fell within the weak range (τ < 0.24). When combining all pre-puberty and post-puberty participants, τ values were in the negligible to very weak range for all tests. CONCLUSION: The strength of relationship between body mass index and gross motor capacity as measured by the BOT-2 subtest item scores used in this study is very weak and suggests that they are not clinically relevant.

Comparative genomics of the T cell receptor µ locus in marsupials and monotremes.

T cells are a primary component of the vertebrate adaptive immune system. There are three mammalian T cell lineages based on their T cell receptors (TCR). The αß T cells and γδ T cells are ancient and found broadly in vertebrates. The more recently discovered γµ T cells are uniquely mammalian and only found in marsupials and monotremes. In this study, we compare the TCRµ locus (TRM) across the genomes of two marsupials, the gray short-tailed opossum and Tasmanian devil, and one monotreme, the platypus. These analyses revealed lineage-specific duplications, common to all non-eutherian mammals described. There is conserved synteny in the TRM loci of both marsupials but not in the monotreme. Our results are consistent with an ancestral cluster organization which was present in the last common mammalian ancestor which underwent lineage-specific duplications and divergence among the non-eutherian mammals.

The International Consortium on Primary Graft Dysfunction: Redefining Clinical Risk Factors in the Contemporary Era of Heart Transplantation.

BACKGROUND: Primary graft dysfunction (PGD) is the leading cause of morbidity and mortality early after heart transplantation (HT). The International Consortium on PGD is a multicenter collaboration dedicated to identifying the clinical risk factors for PGD in the contemporary era of HT. The objectives of the current report were (1) to assess the incidence of severe PGD in an international cohort; (2) to evaluate the performance of the most strongly validated PGD risk tool, the RADIAL score, in a contemporary cohort; and (3) to redefine clinical risk factors for severe PGD in the current era of HT. METHODS: This is a retrospective, observational study of consecutive adult HT recipients between 2010 and 2020 in 10 centers in the United States, Canada and Europe. Patients with severe PGD were compared to those without severe PGD (comprising those with no, mild and moderate PGD). The RADIAL score was calculated for each transplant recipient. The discriminatory power of the RADIAL score was evaluated using receiver operating characteristic (ROC) analysis, and its calibration was assessed by plotting the percentage of PGD predicted vs that which was observed. To identify clinical risk factors associated with severe PGD, we performed multivariable mixed-effects logistic regression modeling to account for among-center variability. RESULTS: A total of 2746 patients have been enrolled in the registry to date, including 2015 (73.4%) from North America, and 731 (26.6%) from Europe; 215 participants (7.8%) met the criteria for severe PGD. There was an increase in the incidence of severe PGD over the study period (P value for trend by difference sign test = 0.004). The Kaplan-Meier estimate for 1-year survival was 75.7% (95% CI 69.4-80.9%) in patients with severe PGD as compared to 94.4% (95% CI 93.5-95.2%) in those without severe PGD (log-rank P value < 0.001). The RADIAL score performed poorly in our contemporary cohort and was not associated with severe PGD; it had an AUC of 0.53 (95% CI 0.48-0.58). In the multivariable regression model, acute preoperative dialysis (OR 2.41, 95% CI 1.31-4.43), durable left ventricular assist device support (OR 1.77, 95% CI 1.13-2.77), and total ischemic time (OR 1.20 for each additional hour, 95% CI 1.02-1.41) were associated with an increased risk of severe PGD. CONCLUSIONS: Our consortium has identified an increasing incidence of PGD in the modern transplant era. We identified contemporary risk factors for this early post-transplant complication, which confers a high mortality risk. These results may enable the identification of patients at high risk for developing severe PGD in order to inform peri-transplant donor and recipient management practices.

Predicting renal function response to renal artery stenting.

OBJECTIVE: The Cardiovascular Outcomes in Renal Atherosclerotic Lesions Trial found no benefit of renal artery stenting (RAS) over medical therapy, although it was underpowered to detect a benefit among patients with chronic kidney disease (CKD). A post hoc analysis demonstrated improved event-free survival after RAS for patients whose renal function improved by 20% or more. A significant obstacle to achieving this benefit is the inability to predict which patients' renal function will improve from RAS. The objectives of the current study were to identify predictors of renal function response to RAS. METHODS: The Veteran Affairs Corporate Data Warehouse was queried for patients who underwent RAS between 2000 and 2021. The primary outcome was improvement in renal function (estimated glomerular filtration rate [eGFR]) after stenting. Patients were categorized as responders if the eGFR at 30 days or greater after stenting increased by 20% or more compared with before stenting. All others were nonresponders. RESULTS: The study cohort included 695 patients with a median follow-up of 7.1 years (interquartile range, 3.7-11.6 years). Based on postoperative change in eGFR, 202 stented patients (29.1%) were responders, and the remainder (n = 493 [70.9%]) were nonresponders. Before RAS, responders had a significantly higher mean serum creatinine, lower mean eGFR, and higher rate of decline of preoperative GFR in the months before stenting. After stenting, responders had a 26.1% increase in eGFR, compared with before stenting (P < .0001), which remained stable during follow-up. In contrast, nonresponders had a progressive 5.5% decrease in eGFR after stenting. Logistic regression analysis identified three predictors of renal function response to stenting: (1) diabetes (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.44-0.91; P = .013), (2) CKD stages 3b or 4 (OR, 1.80; 95% CI, 1.26-2.57; P = .001), and (3) rate of decline in preoperative eGFR per week before stenting (OR, 1.21; 95% CI, 1.05-1.39; P = .008). CKD stages 3b and 4 and the rate of decline in preoperative eGFR are positive predictors of renal function response to stenting, whereas diabetes is a negative predictor. CONCLUSIONS: Based on our data, patients in CKD stages 3b and 4 (eGFR 15-44 mL/min/1.73 m2) are the only subgroups with a significant probability of improved renal function after RAS. The rate of decline of preoperative eGFR over the months before stenting is a powerful discriminator of patients who are most likely to benefit from RAS. Specifically, patients with a more rapid decrease in eGFR before stenting have a significantly greater probability of improved renal function with RAS. In contrast, diabetes is a negative predictor of improved renal function, so interventionalists should be circumspect about RAS in diabetic patients.

Chronic kidney disease impacts outcomes after abdominal aortic aneurysm repair.

OBJECTIVE: Chronic kidney disease (CKD) and end-stage renal disease are traditionally associated with worse outcomes after endovascular and open repair of abdominal aortic aneurysm (AAA). This study stratifies outcomes of AAA repair by approach, CKD severity, and dialysis dependence. METHODS: All patients undergoing elective infrarenal open aneurysm repair (OAR) and endovascular aortic repair (EVAR) with preoperative renal function data captured by the Vascular Quality Initiative between January 2003 and September 2020 were analyzed. Patients were stratified by CKD class as follows: CKD stages 1 and 2, CKD stage 3a, CKD stage 3b, CKD stages 4 and 5, and dialysis. Primary outcomes were perioperative and 1-year mortality. Predictors of survival were identified by Cox multivariate regression models. RESULTS: In total, 53,867 elective AAA repairs were identified: 5396 (10%) OARs and 48,471 (90%) EVARs. Most patients were White (90%) and male (81%), with a mean age of 73 ± 9 years. Patients who underwent EVAR were older and had more comorbidities. The use of elective EVAR for AAA increased from 52% in 2003 to 91% in 2020 (P < .001). The OAR cohort had more perioperative complications and short-term mortality. The CKD 1 and 2 group had the highest 1-year survival compared with the other groups after both OAR and EVAR. On Cox regression analysis, after EVAR, compared with CKD 1 and 2, worsening CKD stage (CKD 3a: hazard ratio [HR], 1.25; 95% confidence interval [CI], 0.93-1.68; P = .13; CKD 3b: HR, 1.74; 95% CI, 1.23-2.45; P < .050; CKD 4-5: HR, 3.23; 95% CI, 2.13-4.88; P < .001), and dialysis (HR, 4.48; 95% CI, 1.90-10.6; P < .001) were independently associated with worse 1-year survival rates. After OAR, compared with CKD 1 and 2, worsening CKD stage (CKD 3a: HR, 1.08; 95% CI, 0.96-1.20; P = .20; CKD 3b: HR, 1.60; 95% CI, 1.41-1.81; P < .001; CKD 4-5: HR, 2.85; 95% CI, 2.39-3.41; P < .001), and dialysis (HR, 3.79; 95% CI, 3.01-4.76; P < .001) were independently associated with worse 1-year survival rates. CONCLUSIONS: Regardless of the treatment approach, CKD severity is an important predictor of perioperative and 1-year mortality rates after infrarenal AAA repair and may reflect the natural history of CKD. Open repair is associated with high perioperative mortality risk in patients with CKD stages 4 and 5, as well as end-stage renal disease. Individualization of patient decision-making is especially important in patients with a glomerular filtration rate of less than 45 and perhaps consideration should be given to raising the threshold for elective AAA repair in these patients. Further studies focusing on appropriate size threshold for repair in these patients may be warranted.

Surfactant Adsorption Layers: Experiments and Modeling.

During recent years, great progress has been made in understanding the adsorption of surfactants at liquid interfaces. In addition to tensiometry, new efficient methodologies have been developed, in particular interfacial selective optical methods which allow direct access to the adsorbed amounts and interfacial layer compositions. In addition to these new experimental tools, the thermodynamic description by equations of state now allows one to provide a quantitative picture of surfactant interfacial layers. This is most notable for surfactant layers at water/oil interfaces. Additional knowledge about the structure of interfacial layers was gained through different types of molecular modeling. Improved interrelationships between these three aspects are the challenges for current and future work. Particular attention must be paid to dilational interfacial rheology studies, as these mechanical quantities are much more sensitive to small changes in the interfacial composition and structure.

Novel applications of generative adversarial networks (GANs) in the analysis of ultrafast electron diffraction (UED) images.

Inferring transient molecular structural dynamics from diffraction data is an ambiguous task that often requires different approximation methods. In this paper, we present an attempt to tackle this problem using machine learning. Although most recent applications of machine learning for the analysis of diffraction images apply only a single neural network to an experimental dataset and train it on the task of prediction, our approach utilizes an additional generator network trained on both synthetic and experimental data. Our network converts experimental data into idealized diffraction patterns from which information is extracted via a convolutional neural network trained on synthetic data only. We validate this approach on ultrafast electron diffraction data of bismuth samples undergoing thermalization upon excitation via 800 nm laser pulses. The network was able to predict transient temperatures with a deviation of less than 6% from analytically estimated values. Notably, this performance was achieved on a dataset of 408 images only. We believe that employing this network in experimental settings where high volumes of visual data are collected, such as beam lines, could provide insights into the structural dynamics of different samples.

Liquid application method for time-resolved analyses by serial synchrotron crystallography.

We introduce a liquid application method for time-resolved analyses (LAMA), an in situ mixing approach for serial crystallography. Picoliter-sized droplets are shot onto chip-mounted protein crystals, achieving near-full ligand occupancy within theoretical diffusion times. We demonstrate proof-of-principle binding of GlcNac to lysozyme, and resolve glucose binding and subsequent ring opening in a time-resolved study of xylose isomerase.