Where you live matters: Area deprivation predicts poor survival and liver transplant waitlisting.

Social determinants of health (SDOH) are important predictors of poor clinical outcomes in chronic diseases, but their associations among the general cirrhosis population and liver transplantation (LT) are limited. We conducted a retrospective, multiinstitutional analysis of adult (≥18-years-old) patients with cirrhosis in metropolitan Chicago to determine the associations of poor neighborhood-level SDOH on decompensation complications, mortality, and LT waitlisting. Area deprivation index and covariates extracted from the American Census Survey were aspects of SDOH that were investigated. Among 15 101 patients with cirrhosis, the mean age was 57.2 years; 6414 (42.5%) were women, 6589 (43.6%) were non-Hispanic White, 3652 (24.2%) were non-Hispanic Black, and 2662 (17.6%) were Hispanic. Each quintile increase in area deprivation was associated with poor outcomes in decompensation (sHR [subdistribution hazard ratio] 1.07; 95% CI 1.05-1.10; P < .001), waitlisting (sHR 0.72; 95% CI 0.67-0.76; P < .001), and all-cause mortality (sHR 1.09; 95% CI 1.06-1.12; P < .001). Domains of SDOH associated with a lower likelihood of waitlisting and survival included low income, low education, poor household conditions, and social support (P < .001). Overall, patients with cirrhosis residing in poor neighborhood-level SDOH had higher decompensation, and mortality, and were less likely to be waitlisted for LT. Further exploration of structural barriers toward LT or optimizing health outcomes is warranted.

Transforming the Future of Surgeon-Scientists.

OBJECTIVE: To create a blueprint for surgical department leaders, academic institutions, and funding agencies to optimally support surgeon-scientists. BACKGROUND: Scientific contributions by surgeons have been transformative across many medical disciplines. Surgeon-scientists provide a distinct approach and mindset toward key scientific questions. However, lack of institutional support, pressure for increased clinical productivity, and growing administrative burden are major challenges for the surgeon-scientist, as is the time-consuming nature of surgical training and practice. METHODS: An American Surgical Association Research Sustainability Task Force was created to outline a blueprint for sustainable science in surgery. Leaders from top NIH-sponsored departments of surgery engaged in video and in-person meetings between January and April 2023. A strength, weakness, opportunities, threats analysis was performed, and workgroups focused on the roles of surgeons, the department and institutions, and funding agencies. RESULTS: Taskforce recommendations: (1) SURGEONS: Growth mindset : identifying research focus, long-term planning, patience/tenacity, team science, collaborations with disparate experts; Skill set : align skills and research, fill critical skill gaps, develop team leadership skills; DEPARTMENT OF SURGERY (DOS): (2) MENTORSHIP: Chair : mentor-mentee matching/regular meetings/accountability, review of junior faculty progress, mentorship training requirement, recognition of mentorship (eg, relative value unit equivalent, awards; Mentor: dedicated time, relevant scientific expertise, extramural funding, experience and/or trained as mentor, trusted advisor; Mentee : enthusiastic/eager, proactive, open to feedback, clear about goals; (3) FINANCIAL SUSTAINABILITY: diversification of research portfolio, identification of matching funding sources, departmental resource awards (eg, T-/P-grants), leveraging of institutional resources, negotiation of formalized/formulaic funds flow investment from academic medical center toward science, philanthropy; (4) STRUCTURAL/STRATEGIC SUPPORT: Structural: grants administrative support, biostats/bioinformatics support, clinical trial and research support, regulatory support, shared departmental laboratory space/equipment; Strategic: hiring diverse surgeon-scientist/scientists faculty across DOS, strategic faculty retention/ recruitment, philanthropy, career development support, progress tracking, grant writing support, DOS-wide research meetings, regular DOS strategic research planning; (5) COMMUNITY AND CULTURE: Community: right mix of faculty, connection surgeon with broad scientific community; Culture: building research infrastructure, financial support for research, projecting importance of research (awards, grand rounds, shoutouts); (6) THE ROLE OF INSTITUTIONS: Foundation: research space co-location, flexible start-up packages, courses/mock study section, awards, diverse institutional mentorship teams; Nurture: institutional infrastructure, funding (eg, endowed chairs), promotion friendly toward surgeon-scientists, surgeon-scientists in institutional leadership positions; Expectations: RVU target relief, salary gap funding, competitive starting salaries, longitudinal salary strategy; (7) THE ROLE OF FUNDING AGENCIES: change surgeon research training paradigm, offer alternate awards to K-awards, increasing salary cap to reflect market reality, time extension for surgeon early-stage investigator status, surgeon representation on study section, focused award strategies for professional societies/foundations. CONCLUSIONS: Authentic recommitment from surgeon leaders with intentional and ambitious actions from institutions, corporations, funders, and society is essential in order to reap the essential benefits of surgeon-scientists toward advancements of science.

Clinically relevant cut-points for changes in the Liver Frailty Index are associated with waitlist mortality in patients with cirrhosis.

BACKGROUND & AIMS: Physical frailty is a critical determinant of mortality in patients with cirrhosis and can be objectively measured using the Liver Frailty Index (LFI) that is potentially modifiable.. We aimed to LFI cut-points associated with waitlist mortality. APPROACH & RESULTS: Ambulatory adults with cirrhosis without HCC awaiting liver transplantation (LT) from 9 centers from 2012-2021 for ≥3 months with ≥2 pre-LT LFI assessments were included. The primary explanatory variable was change in LFI from first to second assessments per 3 months (∆LFI); we evaluated clinically-relevant ∆LFI cut-points at 0.1, 0.2, 0.3, and 0.5. The primary outcome was waitlist mortality (death or delisting for being too sick) with transplant considered as a competing event. Among 1029 patients, median (IQR) age was 58 (51-63) years; 42% were female; and median lab MELDNa at first assessment was 18 (15-22). For each 0.1 improvement in ∆LFI, risk of overall mortality decreased by 6% (cause-specific hazard ratio [cHR] 0.94, 95%CI 0.92-0.97, p < 0.001). ∆LFI was associated with waitlist mortality at cut-points as low as 0.1 (cHR 0.63, 95%CI 0.46-0.87) and 0.2 (HR 0.61, 95%CI 0.42-0.87). CONCLUSIONS: An improvement in LFI per 3 months as small as 0.1 in the pre-LT period is associated with a clinically meaningful reduction in waitlist mortality. These data provide estimates of the reduction in mortality risk associated with improvements in LFI that can be used to assess effectiveness of interventions targeting physical frailty in cirrhosis patients.

New synthetic molecules incorporated into polymeric micelles used for treatment against visceral leishmaniasis.

Treatment against visceral leishmaniasis (VL) presents problems, mainly related to drug toxicity, high cost and/or by emergence of resistant strains. In the present study, two vanillin synthetic derivatives, 3 s [4-(2-hydroxy-3-(4-octyl-1H-1,2,3-triazol-1-yl)propoxy)-3-methoxybenzaldehyde] and 3 t [4-(3-(4-decyl-1H-1,2,3-triazol-1-yl)-2-hydroxypropoxy)-3-methoxybenzaldehyde], were evaluated as therapeutic candidates in a murine model against Leishmania infantum infection. Molecules were used pure (3 s and 3 t) or incorporated into Poloxamer 407-based micelles (3 s/M and 3 t/M) in the infected animals, which also received amphotericin B (AmpB) or Ambisome® as control. Results showed that 3 s/M and 3 t/M compositions induced a Th1-type immune response in treated animals, with higher levels of IFN-γ, IL-2, TNF-α, IL-12, nitrite, and IgG2a antibodies. Animals presented also low toxicity and significant reductions in the parasite load in their spleens, livers, bone marrows and draining lymph nodes, as compared as control groups mice, with the evaluations performed one and 30 days after the application of the therapeutics. In conclusion, preliminary data suggest that 3 s/M and 3 t/M could be considered for future studies as therapeutic agents against VL.

The liver frailty index is a predictor of healthcare utilization after liver transplantation in older adults.

BACKGROUND: Older adults have higher healthcare utilization after liver transplantation (LT), yet objective risk stratification tools in this population are lacking. We evaluated the Liver Frailty Index (LFI) as one potential tool. METHODS: Ambulatory LT candidates ≥65 years without hepatocellular carcinoma (HCC) who underwent LT from 1/2012 to 6/2022 at 8 U.S. centers were included. Estimates of the difference in median using quantile regression were used to assess the adjusted association between LFI and hospitalized days within 90 days post-LT. RESULTS: Of 131 LT recipients, median (interquartile range [IQR]) (1st -3rd quartiles) age was 68 years (66-70); median pre-LT MELD-Na was 19 (15-24). Median LFI was 4.1 (3.6-4.7); 27% were frail (LFI≥4.5). Median hospitalized days within 90 days post-LT was 11 (7-20). Compared with non-frail patients, frail patients were hospitalized for a median of 5 days longer post-LT (95% CI .30-9.7, p = .04). Each .5 unit increase in pre-LT LFI was associated with an increase of 1.16 days (95%CI .42-2.69, p = .02) in hospitalized days post-LT. CONCLUSION: Among older adults undergoing LT, frailty was associated with more hospitalized days within 90 days after LT. The LFI can identify older adults who might benefit from pre-LT or early post-LT programs which may reduce post-LT healthcare utilization, such as early rehabilitation or post-hospital discharge programs.

Association of body mass index with post-liver transplant outcomes.

BACKGROUND: Patients with obesity have inferior outcomes after general surgery procedures, but studies evaluating post-liver transplant (LT) outcomes have been limited by small sample sizes or lack of granularity of outcomes. We evaluated the relationship between obesity and post-LT outcomes, including those observed in other populations to be obesity-related. METHODS: Included were 1357 LT recipients prospectively enrolled in the ambulatory pre-LT setting at 8 U.S. CENTERS: Recipient were categorized by body mass index (BMI, kg/m2 ): non-obese (BMI < 30), class 1 obesity (BMI 30-<35), and classes 2-3 obesity (BMI ≥ 35). Post-transplant complications were compared by BMI using Chi-square and rank-sum testing, logistic regression, Kaplan-Meier curves, and Cox regression. RESULTS: Classes 2-3 obesity was associated with higher adjusted odds than non-obesity of venous thrombosis [adjusted odds ratio (aOR) 2.06, 95% CI 1.01-4.23, p = .047] and wound dehiscence (aOR 2.45, 95% CI 1.19-5.06, p = .02). Compared with non-obese recipients, post-LT hospital stay was significantly longer for recipients with classes 2-3 obesity [p = .01; median (Q1-Q3) 9 (6-14) vs. 8 (6-12) days) or class 1 obesity [p = .002; 9 (6-14) vs. 8 (6-11) days].  Likelihood of ICU readmission, infection, discharge to a non-home facility, rejection, 30-day readmission, and 1-year readmission were similar across BMI categories (all p > .05). CONCLUSION: Compared to non-obese recipients, obese recipients had similar post-LT survival but longer hospital stay and higher likelihood of wound dehiscence and venous thrombosis. These findings underscore that obesity alone should not preclude LT, but recipients with obesity should be monitored for obesity-related complications such as wound dehiscence and venous thrombosis.

Utilizing a novel MRI technique to identify adverse muscle composition in end-stage liver disease: A pilot study.

INTRODUCTION AND OBJECTIVES: Sarcopenia is a common complication of end-stage liver disease (ESLD), but its exact relationship to myosteatosis and frailty remains unclear. In this pilot study, we tested the feasibility of a specialized MRI protocol and automated image analysis in patients with ESLD. MATERIALS AND METHODS: In a single-center prospective study, adult liver transplant candidates with ESLD underwent assessment of muscle composition between 3/2022 and 6/2022 using the AMRA® MAsS Scan. The primary outcome of interest was feasibility of the novel MRI technique in patients with ESLD. We also tested if thigh muscle composition correlated with validated measures of frailty and sarcopenia. RESULTS: Eighteen subjects (71 % male, mean age 59 years) were enrolled. The most common etiologies of cirrhosis were alcohol-related liver disease (44 %) and non-alcohol-associated fatty liver disease (33 %), with a mean MELD-Na of 13 (± 4). The mean time needed to complete the MRI protocol was 14.9 min and only one patient could not complete it due to metal hardware in both knees. Forty-one percent of patients had adverse muscle composition (high thigh fat infiltration and low-fat free muscle volume) and these patients were more likely to have undergone a recent large volume paracentesis (43 % vs. 0 %, p < 0.02). The adverse muscle composition group performed significantly worse on the 6-minute walk test compared to the remainder of the cohort (379 vs 470 m, p < 0.01). CONCLUSIONS: The AMRA® MAsS Scan is feasible to perform in patients with ESLD and can be used to quantify myosteatosis, a marker of muscle quality and potentially muscle functionality in ESLD.

Treatment using vanillin-derived synthetic molecules incorporated into polymeric micelles is effective against infection caused by Leishmania amazonensis species.

Treatment against leishmaniasis presents problems, mainly due to the toxicity of the drugs, high cost, and the emergence of resistant strains. A previous study showed that two vanillin-derived synthetic molecules, 3s [4-(2-hydroxy-3-(4-octyl-1H-1,2,3-triazol-1-yl)propoxy)-3-methoxybenzaldehyde] and 3t [4-(3-(4-decyl-1H-1,2,3-triazol-1-yl)-2-hydroxypropoxy)-3-methoxybenzaldehyde], presented antileishmanial activity against Leishmania infantum, L. amazonensis, and L. braziliensis species. In the present work, 3s and 3t were evaluated to treat L. amazonensis-infected mice. Molecules were used pure or incorporated into Poloxamer 407-based micelles. In addition, amphotericin B (AmpB) and its liposomal formulation, Ambisome®, were used as control. Animals received the treatment and, one and 30 days after, they were euthanized to evaluate immunological, parasitological, and biochemical parameters. Results showed that the micellar compositions (3s/Mic and 3t/Mic) induced significant reductions in the lesion mean diameter and parasite load in the infected tissue and distinct organs, as well as a specific and significant antileishmanial Th1-type immune response, which was based on significantly higher levels of IFN-γ, IL-12, nitrite, and IgG2a isotype antibodies. Drug controls showed also antileishmanial action; although 3s/Mic and 3t/Mic have presented better and more significant parasitological and immunological data, which were based on significantly higher IFN-γ production and lower parasite burden in treated animals. In addition, significantly lower levels of urea, creatinine, alanine transaminase, and aspartate transaminase were found in mice treated with 3s/Mic and 3t/Mic, when compared to the others. In conclusion, results suggest that 3s/Mic and 3t/Mic could be considered as therapeutic candidates to treat against L. amazonensis infection.

Therapeutic Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy: Reducing Variability in Practice through a Collaborative Telemedicine Initiative.

OBJECTIVE: This study aimed to assess the viability of implementing a tele-educational training program in neurocritical care for newborns diagnosed with hypoxic-ischemic encephalopathy (HIE) and treated with therapeutic hypothermia (TH), with the goal of reducing practice variation. STUDY DESIGN: Prospective study including newborns with HIE treated with TH from 12 neonatal intensive care units in Brazil conducted from February 2021 to February 2022. An educational intervention consisting of 12 biweekly, 1-hour, live videoconferences was implemented during a 6-month period in all centers. Half of the centers had the assistance of a remote neuromonitoring team. The primary outcome was the rate of deviations from TH protocol, and it was evaluated during a 3-month period before and after the intervention. Logistic regression via generalized estimating equations was performed to compare the primary and secondary outcomes. Protocol deviations were defined as practices not in compliance with the TH protocol provided. A subanalysis evaluated the differences in protocol deviations and clinical variables between centers with and without neuromonitoring. RESULTS: Sixty-six (39.5%) newborns with HIE were treated with TH during the preintervention period, 69 (41.3%) during the intervention period and 32 (19.1%) after intervention. There was not a significant reduction in protocol deviations between the pre- and postintervention periods (37.8 vs. 25%, p = 0.23); however, a decrease in the rates of missing Sarnat examinations within 6 hours after birth was seen between the preintervention (n = 5, 7.6%) and postintervention (n = 2, 6.3%) periods (adjusted odds ratio [aOR]: 0.36 [0.25-0.52], p < 0.001). Centers with remote neuromonitoring support had significantly lower rates of seizures (27.6 vs. 57.5%; aOR: 0.26 [0.12-0.55], p < 0.001) and significant less seizure medication (27.6 vs. 68.7%; aOR: 0.17 [0.07-0.4], p < 0.001). CONCLUSION: This study shows that implementing a tele-educational program in neonatal neurocritical care is feasible and may decrease variability in the delivery of care to patients with HIE treated with TH. KEY POINTS: · Neurocritical care strategies vary widely in low- and middle-income countries.. · Heterogeneity of care may lead to suboptimal efficacy of neuroprotective strategies.. · Tele-education and international collaboration can decrease the variability of neurocritical care provided to infants with HIE..

Frailty, mortality, and health care utilization after liver transplantation: From the Multicenter Functional Assessment in Liver Transplantation (FrAILT) Study.

BACKGROUND AND AIMS: Frailty is a well-established risk factor for poor outcomes in patients with cirrhosis awaiting liver transplantation (LT), but whether it predicts outcomes among those who have undergone LT is unknown. APPROACH AND RESULTS: Adult LT recipients from 8 US centers (2012-2019) were included. Pre-LT frailty was assessed in the ambulatory setting using the Liver Frailty Index (LFI). "Frail" was defined by an optimal cut point of LFI ≥ 4.5. We used the 75th percentile to define "prolonged" post-LT length of stay (LOS; ≥12 days), intensive care unit (ICU) days (≥4 days), and inpatient days within 90 post-LT days (≥17 days). Of 1166 LT recipients, 21% were frail pre-LT. Cumulative incidence of death at 1 and 5 years was 6% and 16% for frail and 4% and 10% for nonfrail patients (overall log-rank p = 0.02). Pre-LT frailty was associated with an unadjusted 62% increased risk of post-LT mortality (95% CI, 1.08-2.44); after adjustment for body mass index, HCC, donor age, and donation after cardiac death status, the HR was 2.13 (95% CI, 1.39-3.26). Patients who were frail versus nonfrail experienced a higher adjusted odds of prolonged LT LOS (OR, 2.00; 95% CI, 1.47-2.73), ICU stay (OR, 1.56; 95% CI, 1.12-2.14), inpatient days within 90 post-LT days (OR, 1.72; 95% CI, 1.25-2.37), and nonhome discharge (OR, 2.50; 95% CI, 1.58-3.97). CONCLUSIONS: Compared with nonfrail patients, frail LT recipients had a higher risk of post-LT death and greater post-LT health care utilization, although overall post-LT survival was acceptable. These data lay the foundation to investigate whether targeting pre-LT frailty will improve post-LT outcomes and reduce resource utilization.

Exploring drug repositioning for leishmaniasis treatment: Ivermectin plus polymeric micelles induce immunological response and protection against tegumentary leishmaniasis.

Leishmania amazonensis can cause a wide spectrum of the clinical manifestations of leishmaniasis in humans. The development of new therapeutics is a long and expensive task; in this context, drug repositioning could be considered a strategy to identify new biological actions of known products. In the present study, ivermectin (IVE) was tested against distinct Leishmania species able to cause disease in humans. In vitro experiments showed that IVE was effective to reduce the infection degree and parasite load in Leishmania donovani- and L. amazonensis-infected macrophages that were treated with it. In addition, using the culture supernatant of treated macrophages, higher production of IFN-γ and IL-12 and lower levels of IL-4 and IL-10 were found. Then, IVE was used in a pure form or incorporated into Poloxamer 407-based polymeric micelles (IVE/M) for the treatment of L. amazonensis-infected BALB/c mice. Animals (n = 16 per group) were infected and later received saline, empty micelles, amphotericin B (AmpB), IVE, or IVE/M. They were euthanized at one (n = 8 per group) and 30 (n = 8 per group) days after treatment and, in both endpoints, immunological, parasitological, and biochemical evaluations were performed. Results showed that both IVE and IVE/M induced higher levels of IFN-γ, IL-12, GM-CSF, nitrite, and IgG2a antibodies, as well as higher IFN-γ expression evaluated by RT-qPCR in spleen cell cultures. Such animals showed low organic toxicity, as well as significant reductions in the lesion's average diameter and parasite load in their infected tissue, spleen, liver, and draining lymph node. The efficacy was maintained 30 days post-therapy, while control mice developed a polarized Th2-type response and high parasite load. In this context, IVE could be considered as a new candidate to be applied in future studies for the treatment against distinct Leishmania species.

Previous infection with SARS-CoV-2 impacts embryo morphokinetics but not clinical outcomes in a time-lapse imaging system.

The goal for the present study was to investigate whether previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may compromise embryo morphokinetics and implantation. For that, a historical cohort study was performed in a private university-affiliated in vitro fertilization center. The study included 1628 embryos from 88 patients undergoing intracytoplasmic sperm injection (ICSI) cycles. Patients were age-matched in a 1:3 ratio to either a coronavirus disease (COVID) group, including patients with a positive SARS-CoV-2 immunoglobulin test (n = 22 patients, 386 embryos), or a control group, including patients with a negative SARS-CoV-2 immunoglobulin test (n = 66, 1242 embryos). The effect of previous infection with SARS-CoV-2 on morphokinetic events and ICSI outcomes was evaluated. Embryos derived from patients in the COVID group presented longer time to pronuclei appearance and fading, time to form two, three, four and five cells, and time to blastulation. The durations of the third cell cycle and to time to complete synchronous divisions were also significantly increased in the COVID group compared with the control group, whereas known implantation diagnosis score Day 5 ranked significantly lower in the COVID group. No differences were observed between the COVID and control groups on clinical outcomes. In conclusion, patients planning parenthood, who have recovered from COVID-19 infection, must be aware of a possible effect of the infection on embryo development potential.

Time-lapse monitoring: An adjunct tool to select embryos for preimplantation genetic testing.

The goal for the present study was to investigate the effect of aneuploidy on embryo morphokinetics events in a time-lapse imaging (TLI) system incubator. This retrospective cohort study was performed in a private university-affiliated in vitro fertilization center, between 2019 March and December 2020. Kinetic data were analyzed in 935 embryos, derived from 316 patients undergoing intracytoplasmic sperm injection cycle with preimplantation genetic testing (PGT) for aneuploidy, individually cultured in a TLI incubator until Day 5 of development. Timing of morphokinetic variables, the incidences of multinucleation, and Known Implantation Data Score (KIDScore)-Day 5 were compared between euploid (n = 352) and aneuploid embryos (n = 583). Aneuploid embryos showed significantly longer timing to complete specific morphokinetic parameters compared to euploidy embryos. Euploidy embryos also showed a significantly higher KIDScore when compared with the aneuploidy ones. Our evidence suggests that TLI monitoring may be an adjunct approach to select embryos for PGT; however, cautious investigation is still needed.

Association Between End-Stage Liver Disease and Incident Heart Failure in an Integrated Health System.

BACKGROUND: End-stage liver disease (ESLD) and heart failure (HF) often coexist and are associated with significant morbidity and mortality. However, the true incidence of HF among patients with ESLD remains understudied. OBJECTIVE: This study aims to evaluate the association between ESLD and incident HF in a real-world clinical cohort. DESIGN AND PARTICIPANTS: A retrospective electronic health records database analysis of individuals with ESLD and frequency-matched controls without ESLD in a large integrated health system. MAIN MEASURES: The primary outcome was incident HF, which was defined by the International Classification of Disease codes and manually adjudicated by physician reviewers. The Kaplan-Meier method was used to estimate the cumulative incidence of HF. Multivariate proportional hazards models adjusted for shared metabolic factors (diabetes, hypertension, chronic kidney disease, coronary heart disease, body mass index) were used to compare the risk of HF in patients with and without ESLD. KEY RESULTS: Of 5004 patients (2502 with ESLD and 2502 without ESLD), the median (Q1-Q3) age was 57.0 (55.0-65.0) years, 59% were male, and 18% had diabetes. Over a median (Q1-Q3) follow-up of 2.3 (0.6-6.0) years, 121 incident HF cases occurred. Risk for incident HF was significantly higher for patients with ESLD compared with the non-ESLD group (adjusted HR: 4.67; 95% CI: 2.82-7.75; p < 0.001), with the majority of the ESLD group (70.7%) having HF with preserved ejection fraction (ejection fraction ≥ 50%). CONCLUSION: ESLD was significantly associated with a higher risk of incident HF, independent of shared metabolic risk factors, with the predominant phenotype being HF with preserved ejection fraction.

Machine learning instructed microfluidic synthesis of curcumin-loaded liposomes.

The association of machine learning (ML) tools with the synthesis of nanoparticles has the potential to streamline the development of more efficient and effective nanomedicines. The continuous-flow synthesis of nanoparticles via microfluidics represents an ideal playground for ML tools, where multiple engineering parameters - flow rates and mixing configurations, type and concentrations of the reagents - contribute in a non-trivial fashion to determine the resultant morphological and pharmacological attributes of nanomedicines. Here we present the application of ML models towards the microfluidic-based synthesis of liposomes loaded with a model hydrophobic therapeutic agent, curcumin. After generating over 200 different liposome configurations by systematically modulating flow rates, lipid concentrations, organic:water mixing volume ratios, support-vector machine models and feed-forward artificial neural networks were trained to predict, respectively, the liposome dispersity/stability and size. This work presents an initial step towards the application and cultivation of ML models to instruct the microfluidic formulation of nanoparticles.

Living donor liver transplant candidate and donor selection and engagement: Meeting report from the living donor liver transplant consensus conference.

INTRODUCTION: Living donor liver transplantation (LDLT) is a promising option for mitigating the deceased donor organ shortage and reducing waitlist mortality. Despite excellent outcomes and data supporting expanding candidate indications for LDLT, broader uptake throughout the United States has yet to occur. METHODS: In response to this, the American Society of Transplantation hosted a virtual consensus conference (October 18-19, 2021), bringing together relevant experts with the aim of identifying barriers to broader implementation and making recommendations regarding strategies to address these barriers. In this report, we summarize the findings relevant to the selection and engagement of both the LDLT candidate and living donor. Utilizing a modified Delphi approach, barrier and strategy statements were developed, refined, and voted on for overall barrier importance and potential impact and feasibility of the strategy to address said barrier. RESULTS: Barriers identified fell into three general categories: 1) awareness, acceptance, and engagement across patients (potential candidates and donors), providers, and institutions, 2) data gaps and lack of standardization in candidate and donor selection, and 3) data gaps regarding post-living liver donation outcomes and resource needs. CONCLUSIONS: Strategies to address barriers included efforts toward education and engagement across populations, rigorous and collaborative research, and institutional commitment and resources.

Epidemiology of delirium in hospitalized patients in Latin America: A systematic review.

BACKGROUND: Accurate epidemiological data are essential for the planning of policies aimed at the identification, prevention, and management of delirium. The reported occurrence of delirium in hospitalized patients varies widely among studies, ranging between 5% to more than 80% in the international literature. The exact occurrence in Latin America is not well described. OBJECTIVE: The aim of this study is to conduct a systematic analysis of the published data on the epidemiology of delirium in hospitalized patients in Latin America. METHODS: We conducted a systematic review following PRISMA guidelines. Both MEDLINE and LILACS databases were searched for original research articles reporting the occurrence of delirium among adult hospitalized patients in Latin American countries. Studies including pediatric populations were excluded from this analysis. Two authors independently applied eligibility criteria, assessed quality, and extracted data. The corresponding authors of the original articles were contacted to obtain relevant information about the study when this was not present in the published manuscripts. RESULTS: Seven hundred and eighteen original articles were identified. After screening titles and abstracts, 149 studies were included in the final analysis. The occurrence of delirium varied depending on the clinical scenario: (1) in the general medico-surgical wards, it ranged from 2.1% to 60.4%, (2) in the Intensive Care Units (ICUs), from 9.6% to 94.8%, (3) in the post-operatory population, from 5.45% and 52.3%, and (4) it was found to be between 10.7% and 62% in the emergency department setting. The most used delirium assessment tools were the "Confusion Assessment Method" (CAM; in the general population), and the "Confusion Assessment Method for the ICU" (CAM-ICU). Fourteen out of 149 studies were conducted in clinical settings who actively implemented some form of non-pharmacological delirium prevention bundles, most of them as part of ICU sedation-analgesia protocols. CONCLUSION: Delirium occurs frequently in hospitalized patients in Latin America throughout a variety of clinical scenarios, including ICU, general wards, post-operatory populations, and among the emergency department setting. The CAM and the CAM-ICU are the most used delirium assessment tools. Bundles of non-pharmacological interventions to prevent delirium are not universally implemented.

National Cancer Institute Imaging Data Commons: Toward Transparency, Reproducibility, and Scalability in Imaging Artificial Intelligence.

The remarkable advances of artificial intelligence (AI) technology are revolutionizing established approaches to the acquisition, interpretation, and analysis of biomedical imaging data. Development, validation, and continuous refinement of AI tools requires easy access to large high-quality annotated datasets, which are both representative and diverse. The National Cancer Institute (NCI) Imaging Data Commons (IDC) hosts large and diverse publicly available cancer image data collections. By harmonizing all data based on industry standards and colocalizing it with analysis and exploration resources, the IDC aims to facilitate the development, validation, and clinical translation of AI tools and address the well-documented challenges of establishing reproducible and transparent AI processing pipelines. Balanced use of established commercial products with open-source solutions, interconnected by standard interfaces, provides value and performance, while preserving sufficient agility to address the evolving needs of the research community. Emphasis on the development of tools, use cases to demonstrate the utility of uniform data representation, and cloud-based analysis aim to ease adoption and help define best practices. Integration with other data in the broader NCI Cancer Research Data Commons infrastructure opens opportunities for multiomics studies incorporating imaging data to further empower the research community to accelerate breakthroughs in cancer detection, diagnosis, and treatment. Published under a CC BY 4.0 license.

Chronic kidney disease in patients with childhood-onset systemic lupus erythematosus.

BACKGROUND: Lupus nephritis (LN) is a frequent manifestation of childhood-onset systemic lupus erythematosus (cSLE) with a potential risk for kidney failure and poor outcomes. This study aimed to evaluate stages III, IV, and V of chronic kidney disease (CKD) and investigate risk factors for CKD in cSLE patients. METHODS: We performed a nationwide observational cohort study in 27 pediatric rheumatology centers, including medical charts of 1528 cSLE patients. Data were collected at cSLE diagnosis, during follow-up, and at last visit or death, between September 2016 and May 2019. RESULTS: Of 1077 patients with LN, 59 (5.4%) presented with CKD, 36/59 (61%) needed dialysis, and 7/59 (11.8%) were submitted for kidney transplantation. After Bonferroni's correction for multiple comparisons (p < 0.0013), determinants associated with CKD were higher age at last visit, urinary biomarker abnormalities, neuropsychiatric involvement, higher scores of disease activity at last visit and damage index, and more frequent use of methylprednisolone, cyclosporine, cyclophosphamide, and rituximab. In the regression model analysis, arterial hypertension (HR = 15.42, 95% CI = 6.12-38.83, p ≤ 0.001) and biopsy-proven proliferative nephritis (HR = 2.83, 95%CI = 1.70-4.72, p ≤ 0.001) increased the risk of CKD, while children using antimalarials had 71.0% lower CKD risk ((1.00-0.29) × 100%) than children not using them. The Kaplan-Meier comparison showed lower survival in cSLE patients with biopsy-proven proliferative nephritis (p = 0.02) and CKD (p ≤ 0.001). CONCLUSIONS: A small number of patients manifested CKD; however, frequencies of dialysis and kidney transplantation were relevant. This study reveals that patients with cSLE with hypertension, proliferative nephritis, and absence of use of antimalarials exhibited higher hazard rates of progression to CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

INTRAOCULAR INFLAMMATION INCIDENCE AFTER INTRAVITREAL BROLUCIZUMAB INJECTION FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

PURPOSE: We evaluated the clinical outcomes of intraocular inflammation (IOI) of eyes with neovascular age-related macular degeneration (AMD) injected with brolucizumab in our tertiary referral center. METHODS: A retrospective case series for which clinical records of all eyes that received intravitreal brolucizumab at Bascom Palmer Eye Institute between December 1, 2019, and April 1, 2021, were reviewed. RESULTS: There were 345 eyes of 278 patients who received 801 brolucizumab injections. IOI was detected in 16 eyes of 13 patients (4.6%). In those patients, baseline Logarithm of Minimu Angle of Resolution (logMAR) best-corrected visual acuity was 0.32 0.2 (20/42), while it was 0.58 0.3 (20/76) at IOI presentation. The mean number of injections among eyes experiencing IOI was 2.4, and the interval between the last brolucizumab injection and IOI presentation was 20 days. There was no known case of retinal vasculitis. Management of IOI included topical steroids in seven eyes (54%), topical and systemic steroids in five eyes (38%), and observation in one eye (8%). Best-corrected visual acuity returned to baseline and inflammation resolved in all eyes by the last follow-up examination. CONCLUSION: Intraocular inflammation after brolucizumab injection for neovascular AMD was not uncommon. Inflammation resolved in all eyes by the last follow-up visit.