What's the CATCH? A Participatory Learning Model for Case Review Rounds to Support a Culture of Safety and Quality Improvement in Pediatric Hospital Medicine.

OBJECTIVE: To evaluate the effectiveness of a new model, Case Analysis and Translation to Care in Hospital (CATCH), for the review of pediatric inpatient cases when an adverse event or "close call" had occurred. STUDY DESIGN: The curricular intervention consisted of an introductory podcast/workshop, mentorship of presenters, and monthly CATCH rounds over 16 months. The study was conducted with 22 pediatricians at a single tertiary care center. Intervention assessment occurred using participant surveys at multiple intervals: pre/post the intervention, presenter experience (post), physicians involved and mentors experience (post), and after each CATCH session. Paired t-tests and thematic analysis were used to analyze data. Time required to support the CATCH process was used to assess feasibility. RESULTS: Our overall experience and data revealed a strong preference for the CATCH model, high levels of engagement and satisfaction with CATCH sessions, and positive presenter as well as physicians-involved and mentor experiences. Participants reported that the CATCH model is feasible, engages physicians, promotes a safe learning environment, facilitates awareness of tools for case analysis, and provides opportunities to create "CATCH of the Day" recommendations to support translation of learning to clinical practice. CONCLUSIONS: The CATCH model has significant potential to strengthen clinical case rounds in pediatric hospital medicine. Future research is needed to assess the effectiveness of the model at additional sites and across medical specialities.

Investigation of Optimum Production Conditions and the Stability of ß-Cyclodextrin-Perfluorocarbon Nanocone Clusters for Histotripsy Applications.

Nanocone clusters (NCCs) have been developed as clusters with inclusion complexes of FDA-approved ß-cyclodextrin (ßCD) and perfluorocarbons (PFC) (i.e., perfluoropentane (PFP) and perfluorohexane (PFH)) and have shown promise in nanoparticle-mediated histotripsy (NMH) applications owing to their lowered cavitation threshold, ease of production, and fluorocarbon quantification. However, there is still a lack of information on the best conditions of the synthesis of NCCs as a product that can have a maximum determinable fluorocarbon content and maintain the stability of the NCC during synthesis and when used as histotripsy agents or exposed to physiological conditions. These concerns about the stability of the clusters and the best possible formulation are investigated in the current work. The cluster formation potential was tested taking into consideration the nature of both PFCs and ßCD by employing different synthesis conditions in terms of solution and environmental parameters such as concentration of solvent, stoichiometry between ßCD and PFCs, temperature, pH, solvent type, etc. The best route of synthesis was then translated into various batch sizes and investigated in terms of the PFC loading and yield. These studies revealed that preparing NCCs in double-distilled water in an ice bath at the optimized solution concentration gave the highest yields and optimal PFC loading, as determined from gas chromatography. Furthermore, the stability of the clusters with different stoichiometries was scrutinized in varying concentrations, mechanical disruption times, pH levels, and temperature conditions, showing effects on each cluster's particle size in dynamic light scattering, visualized in transmission electron microscopy, and cavitation behavior in agarose gel tissue phantoms. These studies revealed stable clusters for all formulations, with PFH-containing NCCs emerging to be the most stable in terms of their cluster size and bubble formation potential in histotripsy. Finally, the shelf life of these clusters was investigated using DLS, which revealed a stable cluster. In conclusion, NCCs have shown high stability in terms of both synthesis, which can be replicated in gram-level production, and the cluster itself, which can be exposed to harsher conditions and still form stable bubbles in histotripsy.

Incorporation of ChatGPT and Other Large Language Models into a Graduate Level Computational Bioengineering Course.

The remarkable capabilities of generative artificial intelligence and large language models (LLMs) such as ChatGPT have delighted users around the world. Educators have regarded these tools as either a cause for great concern, an opportunity to educate students on cutting-edge technology, or often some combination of the two. Throughout the Fall 2023 semester, we explored the use of ChatGPT (and Bard, among other LLMs) in a graduate level numerical and statistical methods course for PhD-level bioengineers. In this article we share examples of this ChatGPT content, our observations on what worked best in our course, and speculate on how bioengineering students may be best served by this technology in the future.

Is high salt intake inducing obesity via production of cortisol? A novel working hypothesis and pilot study.

PURPOSE: Evidence is growing that high salt intake is an independent risk factor for obesity, but the mechanisms are unknown. Our novel working hypothesis is that high salt intake drives cortisol production, which in turn, drives obesity. The current study aimed to demonstrate an acute cortisol response following a single high salt meal. METHODS: Eight participants (age 30.5 ± 9.8 years [mean ± SD], 50% female), consumed high salt (3.82 g; 1529 mg sodium) and low salt (0.02 g; 9 mg sodium) meals in a randomized cross-over design. RESULTS: Urinary and salivary cortisol and plasma adrenocorticotropic hormone (ACTH) demonstrated order effects. When high salt was given second, there was a peak above baseline for urinary cortisol (26.3%), salivary cortisol (9.4%) and plasma ACTH (4.1%) followed by a significant decline in each hormone (treatment*time, F[9, 18] = 2.641, p = 0.038, partial η2 = 0.569; treatment*time, F[12, 24] = 2.668, p = 0.020, partial η2 = 0.572; treatment*time, F[12, 24] = 2.580, p = 0.023, partial η2 = 0.563, respectively), but not when high salt was given first (p > 0.05 for all). CONCLUSION: These intriguing findings provide partial support for our hypothesis and support a need for further research to elucidate the role of high salt intake in cortisol production and, in turn, in the aetiology of obesity. TRIAL REGISTRATION NUMBER: ACTRN12623000490673; date of registration 12/05/2023; retrospectively registered.

International consensus recommendations on face transplantation: A 2-step Delphi study.

Face transplantation is a viable reconstructive approach for severe craniofacial defects. Despite the evolution witnessed in the field, ethical aspects, clinical and psychosocial implications, public perception, and economic sustainability remain the subject of debate and unanswered questions. Furthermore, poor data reporting and sharing, the absence of standardized metrics for outcome evaluation, and the lack of consensus definitions of success and failure have hampered the development of a "transplantation culture" on a global scale. We completed a 2-round online modified Delphi process with 35 international face transplant stakeholders, including surgeons, clinicians, psychologists, psychiatrists, ethicists, policymakers, and researchers, with a representation of 10 of the 19 face transplant teams that had already performed the procedure and 73% of face transplants. Themes addressed included patient assessment and selection, indications, social support networks, clinical framework, surgical considerations, data on patient progress and outcomes, definitions of success and failure, public image and perception, and financial sustainability. The presented recommendations are the product of a shared commitment of face transplant teams to foster the development of face transplantation and are aimed at providing a gold standard of practice and policy.

Deaf patients' preferred communication in clinical settings: implications for healthcare providers.

Deaf patients who communicate in American Sign Language (ASL) experience communication challenges leading to medical errors, treatment delays, and health disparities. Research on Deaf patient communication preferences is sparse. Researchers conducted focus groups based on the Health Belief Model with culturally Deaf patients and interpreters. The ASL focus groups were interpreted and transcribed into written English, verified by a third-party interpreting agency, and uploaded into NVivo. Deductive coding was used to identify communication methods and inductive coding was used to identify themes within each. Writing back-and-forth introduced challenges related to English proficiency, medical terminology, poor penmanship, and tendencies of providers to abbreviate. Participants had various speechreading abilities and described challenges with mask mandates. Multiple issues were identified with family and friends as proxy interpreters, including a lack of training, confidentiality issues, emotional support, and patient autonomy. Video remote interpreter challenges included technical, environmental, and interpreter qualification concerns. Participants overwhelmingly preferred on-site interpreters for communication clarity. While there was a preference for direct care, many acknowledged this is not always feasible due to lack of providers fluent in ASL. Access to on-site interpreters is vital for many Deaf patients to provide full access to critical medical information. Budget allocation for on-call interpreters is important in emergency settings.

Outcomes and Complications After Bone Marrow Aspirate Harvest From the Calcaneus.

Background: Bone marrow aspirate (BMA) is used with the putative goal of enhancing healing of injured tissue. The most common sites to harvest BMA are the iliac crest, the tibia, and the calcaneus. Investigators have found that the tibia and calcaneus have fewer progenitor cells than the iliac crest. This retrospective review evaluates the efficacy and safety profile of harvesting BMA from the calcaneus bone. We hypothesized that harvesting BMA from the calcaneus will have high efficacy and safety profile with low complication rates. Methods: A retrospective chart review of patients undergoing bone marrow aspiration from the calcaneus bone from January 2019 to October 2022 was performed. The main data points evaluated were patient satisfaction and pain level, follow-up times, quantity of BMA harvested, fusion rates, and complications including nerve damage, infections, and nonunions. Results: There were 45 (34 female and 11 male) patients who underwent 45 procedures. The average age, BMI, and amount of BMA were 45.1 years (range 23-79), 33.1 (range 19.2-61.3), and 10.3 mL (range 2-40), respectively. There was no pain reported at the final follow-up in 32 patients (71.1%), and there was minimal to no pain in the area of surgery in the remaining 13 patients (28.9%). The 10 cases of fusion successfully healed with combined use of allograft and BMA. The average follow-up time was 12.3 months (range 2.4-33.7). There were no infections, wound complications, or nerve injuries. Conclusion: Harvesting BMA from the calcaneus bone is a safe procedure. In this heterogenous series where BMA augmented other surgical strategies, patients had little to no pain and there were no cases of wound complication or iatrogenic neuropraxia after undergoing bone marrow harvest from the calcaneus. Level of Evidence: Level IV, case series.

Access to inclusive and culturally sensitive mental healthcare in Black, Indigenous, and People of Color pharmacy students and residents.

PURPOSE: Disparities in accessing culturally sensitive mental healthcare exist and may be exacerbated in pharmacy trainees. The purpose of this study was to identify barriers to culturally sensitive mental healthcare and how to improve access for racially and ethnically minoritized pharmacy students and residents. METHODS: This institutional review board-exempt study included in-person and virtual focus groups. Eligible participants were first-, second-, third-, and fourth-year doctor of pharmacy (PharmD) students and pharmacy residents completing a postgraduate year 1 or 2 program who identified as Black, Indigenous, and People of Color (BIPOC). Barriers to care, identity's influence on seeking care, and areas in which the training programs are doing well or areas for improvement were assessed. Responses were transcribed and analyzed using an open coding system by 2 reviewers, followed by discussion as a team to reach consensus. RESULTS: This study enrolled 8 first-year, 5 second-year, 7 third-year, and 2 fourth-year PharmD students and 4 residents (N = 26). Barriers to care included time, access to resources, and internal and external stigma. Identity barriers included cultural and family stigma and lack of representation in therapists with regard to race, ethnicity, and gender. Areas going well included supportive faculty and paid time off, while areas for improvement included wellness days, reduced workload, and increased diversity within the workforce. CONCLUSION: This study is the first to identify barriers to culturally sensitive mental healthcare in pharmacy trainees who identify as BIPOC while providing insight on how to increase culturally sensitive mental healthcare resources.

A Bitter Taste Receptor as a Novel Molecular Target on Cancer-Associated Fibroblasts in Pancreatic Ductal Adenocarcinoma.

Cancer-associated fibroblasts (CAFs) execute diverse and complex functions in cancer progression. While reprogramming the crosstalk between CAFs and cancer epithelial cells is a promising avenue to evade the adverse effects of stromal depletion, drugs are limited by their suboptimal pharmacokinetics and off-target effects. Thus, there is a need to elucidate CAF-selective cell surface markers that can improve drug delivery and efficacy. Here, functional proteomic pulldown with mass spectrometry was used to identify taste receptor type 2 member 9 (TAS2R9) as a CAF target. TAS2R9 target characterization included binding assays, immunofluorescence, flow cytometry, and database mining. Liposomes conjugated to a TAS2R9-specific peptide were generated, characterized, and compared to naked liposomes in a murine pancreatic xenograft model. Proof-of-concept drug delivery experiments demonstrate that TAS2R9-targeted liposomes bind with high specificity to TAS2R9 recombinant protein and exhibit stromal colocalization in a pancreatic cancer xenograft model. Furthermore, the delivery of a CXCR2 inhibitor by TAS2R9-targeted liposomes significantly reduced cancer cell proliferation and constrained tumor growth through the inhibition of the CXCL-CXCR2 axis. Taken together, TAS2R9 is a novel cell-surface CAF-selective target that can be leveraged to facilitate small-molecule drug delivery to CAFs, paving the way for new stromal therapies.

The potential fire risk of emollients when dried on viscose bandages.

BACKGROUND: the potential fire risk of fabrics impregnated with emollients has been described within the health service, including ignition of bandages. The role of emollients in fire fatalities have also been included in coroner reports, as accelerating fires when present. AIMS: although changes in burning behaviour is known, no standard tests have been carried out on bandages which are often used in conjunction with emollients. METHOD: using a standard vertical flammability test, the flammability of viscose bandage was compared to when impregnated with nine dried on emollients with low to high and non-paraffin content. FINDINGS: the time to ignition was significantly reduced with an emollient present and the glowing time was longer. CONCLUSIONS: the same safety advice applies to viscose bandages as other fabrics with emollients; do not expose them to naked flames or high heat sources or allow emollients to build up on bandages.

Transition to retirement: The lived experiences of adults with intellectual disabilities.

BACKGROUND: Adults with intellectual disabilities are living longer and experiencing retirement. However, research about retirement experiences is limited. METHOD: This qualitative study used semi-structured interviews with 10 retired/retiring U.S. adults with intellectual disabilities and an ally of their choice. RESULTS: Participants described factors that pushed or pulled them into retirement, such as health issues or wanting to spend more time with family. Individuals in community work settings described greater self-determination in their decision to retire. Regardless of reasons for retiring, all participants described initial difficulties with adjusting to retirement but over time people's situation, including their mental and physical health, reportedly improved. CONCLUSION: Retirement is a significant life transition. More attention is needed about planning and developing age-appropriate and person-cantered inclusive retirement options for older adults with intellectual disabilities, similar to the transition into adulthood and work life.

Piglets' behaviour and performance in relation to sow characteristics.

The importance of maternal care in commercial pig production is largely ignored. The sow has little possibility to interact with her piglets, and piglets are often subjected to early weaning or artificial rearing. This study aimed to investigate aspects of physiological and behavioural maternal provisioning that contribute to offspring outcomes. We hypothesised that better maternal care and nutritional provisioning would relate positively to piglet immunity, growth and behaviour. Nineteen sows and their litters were studied in free-farrowing pens. Oxytocin and tumour necrosis factor-α in colostrum/milk and salivary cortisol were sampled from sows throughout lactation. Sows were assessed for dominance rank, response to handling, maternal defensiveness, suckling initiation and termination, posture and sow-piglet contact. Piglets were weighed, measured for body mass index (BMI) and sampled for blood (Immunoglobulin G; at birth). After weaning, they experienced a human approach test (HAT) and novel object test. Correlations were explored between individual sow characteristics, individual piglet outcomes, and between sow characteristics and piglet outcomes averaged by litter. Significant correlations between sow and piglet factors were analysed at the litter level in mixed models with piglet outcomes as response variables and sow characteristics as predictor variables, while accounting for sow parity, litter size and batch. Litters grew faster when their sow had lower cortisol values (P = 0.03), while sows with lower cortisol levels had more successful suckling bouts and engaged in greater amounts of sow-piglet contact. Litters had a lower BMI at weaning when the sow had a higher milk fat percentage at d3. Litters of the most dominant sows took longer to approach the human in the HAT, while litters of sows with higher cortisol at d0 took longer to approach the novel object when assessed on correlations (r = 0.82, P < 0.001) but not when the model accounted for parity and litter size (P = 0.35). Only some of the measured nutritive and non-nutritive sow factors influenced litter performance and behaviour, with parity and litter size also playing a role. Given the continued increase in litter size, but also the interest in loose-housed lactation pens for sows, further research on sows' maternal investment and how it can be optimised is warranted.

The effect of exercise on cytokine concentration in equine autologous conditioned serum.

BACKGROUND: Autologous conditioned serum (ACS) is a commonly administered intra-articular treatment for the management of osteoarthritis in athletic horses. OBJECTIVES: To investigate the influence of exercise on the concentration of cytokines in a non-commercial method of ACS production. STUDY DESIGN: Non-randomised cross over design. METHODS: Whole blood was obtained from eight healthy Standardbred horses immediately prior to, 1 h and 24 h following a single bout of exhaustive exercise. Blood was processed using a non-commercial method of ACS production. Fluorescent microsphere immunoassay (FMIA) analysis was performed to quantify Interleukin 1 receptor antagonist (IL-1Ra), Interleukin-10 (IL-10), Interleukin 1ß (IL-1ß) and tumour necrosis factor α (TNF-α) concentrations at each time point. Mixed effect repeated measures analysis of variance (ANOVA) was used to compare the pre-exercise and post-exercise cytokine concentrations. Significance was set at P < 0.05. RESULTS: A reduced concentration of IL-1Ra (median 584.4, IQR 81.9-5098 pg/ml, p = 0.004) and an increased concentration of TNF-α (11.92, 9.28-39.75 pg/ml, P = .05) at 1 h post-exercise were observed when compared with baseline values (IL-Ra 7349, 1272-10 760 pg/ml; TNF TNF-α 11.16, 8.36-32.74 pg/ml). No difference in cytokine concentrations of IL-10 or IL-1ß were found between any of the time points. MAIN LIMITATIONS: The large biological variability and small sample size represents limitations of this study. CONCLUSIONS: These results suggest that a single bout of intense exercise can reduce the concentration of the anti-inflammatory cytokine IL-1Ra and increase the concentration of the pro-inflammatory cytokine TNF-α, reducing the 'anti-inflammatory' cytokine composition of ACS. Our findings suggest that collection of blood for ACS production should be performed no sooner than 24 h following a single episode of intense exercise.

INTRODUCTION/CONTEXTE: Le sérum autologue conditionné (ACS) est fréquemment administré de façon intra-articulaire dans les cas d'ostéoarthrose chez l'athlète équin. OBJECTIFS: Tait d'Investiguer l'influence de l'exercice sur la concentration des cytokines dans l'ACS produit de façon non-commerciale. TYPE D'ÉTUDE: Étude croisée non-aléatoire. MÉTHODES: Le sang entier de 8 chevaux Standardbred en santé a été prélevé immédiatement, 1 heure et 24 heures suivant un seul épisode d'exercice intense. Le sang a été traité en utilisant une méthode de production d'ACS non-commercialisée. Une analyse par test immunologique à microsphères (FMIA, fluorescent microsphere immunoassay) a été effectuée afin de quantifier la concentration dans le temps du récepteur antagoniste de l'interleukine 1 (IL-1Ra), interleukine 10 (IL-10), interleukine 1 beta (IL-1ß) et du facteur de nécrose tumorale alpha (TNF-α). Une analyse de variance ajustée par mesures répétées à effets mixtes a été utilisée pour comparer les concentrations de cytokines avant et après l'exercice. Les données avec une valeur de p < 0.05 ont été considérées significatives. RÉSULTATS: Une concentration diminuée d'IL-1Ra (médiane 584.4, IIQ 81.9-5098 pg/ml, p = 0.004) et une concentration augmentée de TNF-α (11.92, 9.28-39.75 pg/ml, p = 0.05) ont été observées 1 heure après l'exercice par rapport aux valeurs de base (IL-1Ra 7349, 1272-10760 pg/ml; TNF-α 11.16, 8.36-32.74 pg/ml). Aucune différence de concentration de cytokines dans le temps n'a été identifiée pour IL-10 et IL-1ß. LIMITES PRINCIPALES: Grande variabilité biologique et petite taille d'échantillon. CONCLUSIONS: Ces résultats suggère qu'une seule séance d'exercice intense puisse réduire la concentration de la cytokine anti-inflammatoire IL-1Ra et augmenter la concentration de la cytokine pro-inflammatoire TNF-α, ce qui réduirait la composition en cytokines anti-inflammatoires dans l'ACS. Nos trouvailles suggèrent que le prélèvement de sang pour la production d'ACS devrait être fait au moins 24 heures suivant une période d'exercice.

Inheritance of Stress Responses via Small Non-Coding RNAs in Invertebrates and Mammals.

While reports on the generational inheritance of a parental response to stress have been widely reported in animals, the molecular mechanisms behind this phenomenon have only recently emerged. The booming interest in epigenetic inheritance has been facilitated in part by the discovery that small non-coding RNAs are one of its principal conduits. Discovered 30 years ago in the Caenorhabditis elegans nematode, these small molecules have since cemented their critical roles in regulating virtually all aspects of eukaryotic development. Here, we provide an overview on the current understanding of epigenetic inheritance in animals, including mice and C. elegans, as it pertains to stresses such as temperature, nutritional, and pathogenic encounters. We focus on C. elegans to address the mechanistic complexity of how small RNAs target their cohort mRNAs to effect gene expression and how they govern the propagation or termination of generational perdurance in epigenetic inheritance. Presently, while a great amount has been learned regarding the heritability of gene expression states, many more questions remain unanswered and warrant further investigation.

Bioconjugated ß-Cyclodextrin-Perfluorohexane Nanocone Clusters as Functional Nanoparticles for Nanoparticle-Mediated Histotripsy.

Nanocone clusters (NCCs) are new-generation agents of nanoparticle-mediated histotripsy (NMH) recently developed to address the limitations of previously designed nanodroplets (NDs). NCCs can be obtained by simply mixing FDA-approved cyclodextrins (CD) and suitable perfluorocarbons (PFCs), which result in smaller size aggregates, detectable PFC amount, and more stable long-term storage since the obtained powder can be stored and redispersed as needed. Previous experimental and computational studies showed that NCCs consist of an organization of inclusion complexes of CD and PFC around free PFC droplets, and their aggregate behavior depends on the localization of PFC in the cavity and the water solubility of CD derivatives. It has been shown that ß-cyclodextrin (ßCD) and perfluorohexane (PFH) are ideal candidates for NCCs that can be isolated as a powder with high PFC content among various CD and PFC derivatives. This study focuses on the further development of the selected NCC composition to enhance the potential of NMH therapy while also enabling more detailed future experiments in vitro and in vivo. It is aimed to show the bioconjugation potential of NCCs through the example of the most commonly used functionalization methods such as targeting, PEGylation, and fluorescent labeling. For this purpose, ßCD as a building block was monofunctionalized with groups such as azide, alkyne, and amine groups that allow for effective coupling reactions such as the "click" reaction and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride/N-hydroxysuccinimide (EDC/NHS) coupling. These monofunctional ßCDs were used as building blocks of NCCs in the presence of PFH to obtain functional NCCs as precursors of bioconjugation. EPPT1 as a synthetic peptide specific to uMUC1 and folic acid (FA) as the most commonly used targeting agent along with PEGylation were successfully shown as bioconjugation examples. Lastly, fluorescently labeled NCCs were obtained via fluorescein isothiocyanate (FITC) and alkyne functional NCC reaction through propargyl amine and isothiocyanate group reaction. The obtained bioconjugates were tested in vitro to validate the conjugation, and the ability to lower the histotripsy cavitation threshold, which is necessary for NMH, was demonstrated for all bioconjugates. Overall, the results showed that all obtained bioconjugates successfully lowered the cavitation threshold pressure while also fulfilling the desired bioconjugation metrics to serve as improved tools to enhance NMH as a targeted noninvasive ablation method.

Low-dose adjuvant dexmedetomidine did not decrease propofol sedation requirements in children undergoing gastrointestinal endoscopy.

BACKGROUND: Propofol is the cornerstone of deep sedation during pediatric esophagogastroduodenoscopy (EGD), though adjuvant dexmedetomidine may provide propofol-sparing benefits. OBJECTIVE: The objective of the study was to evaluate whether adjuvant dexmedetomidine decreases the total propofol dose in pediatric patients undergoing EGD. METHODS: This single-center, retrospective, cohort study evaluated the total propofol dose in pediatric patients undergoing EGD with and without the use of adjuvant dexmedetomidine. Secondary outcomes included the change in hemodynamics across the perioperative continuum and post-procedure recovery time. A multivariable general linear regression was performed to identify associated variables for recovery time post-procedure. RESULTS: A total of 159 patients were included in the study; 88 patients received dexmedetomidine and propofol (DEX-PRO), and 71 patients received propofol only (PRO). The median [interquartile range (IQR)] propofol dose in the DEX-PRO group was 0.26 [IQR, 0.17-0.36] mg kg-1  min-1 which was not significantly different than the PRO group at 0.27 [IQR, 0.21-0.34] mg kg-1  min-1 , p = 0.730. Evaluation of secondary end points showed the DEX-PRO group had more cases of post-anesthesia care unit (PACU) hypotension (61% vs. 34%, p = 0.001) and a longer recovery time (32.9 ± 14.1 vs. 25.6 ± 10.8 min, p < 0.001) versus the PRO group, respectively. Multivariable linear regression demonstrated that age and the use of dexmedetomidine were associated with prolonged recovery. CONCLUSION: Adjuvant dexmedetomidine did not reduce propofol requirements compared with propofol alone in pediatric patients undergoing EGD. More hypotension and a longer postoperative recovery time were also seen in patients receiving adjuvant dexmedetomidine for their endoscopic procedure.

Experimental and Computational Investigation of Clustering Behavior of Cyclodextrin-Perfluorocarbon Inclusion Complexes as Effective Histotripsy Agents.

Recently developed nanocones (NCs), which are inclusion complexes that are made up of cyclodextrins (CDs) and perfluorocarbons (PFCs), have shown promising results in nanoparticle-mediated histotripsy (NMH) applications due to stable inclusion complexation, PFC quantification, simple synthesis, and processing. FDA-approved ßCD and its modified versions such as low-degree methylated ßCD have been previously demonstrated as prime examples of structures capable of accommodating PFC molecules. However, the complex formation potential of different CDs with various cavity sizes in the presence of PFC molecules, and their consequent aggregation, needs to be explored. In the present study, the complexation and aggregation potential of some natural CDs and their respective derivatives either exposed to perfluoropentane (PFP) or perfluorohexane (PFH) were studied in the wet lab. Computational studies were also performed to account for the limitations faced in PFC quantification because of the low optical density of PFCs within the CD complex and to discover the best candidate for NMH applications. All results revealed that only ßCD and γCD (except HMγCD) derivatives form an inclusion complex with PFCs and only LMßCD, ßCD, and γCD form nanocone clusters (NCCs), which precipitate and can be collected for use. Furthermore, the data collectively show that ßCD and PFCs have the best complexation due to stable complex formation, ease of production, and product recovery, especially with PFH as a more suitable candidate due to its high boiling point, which allows workability during synthesis. Although simulations suggest that highly stable inclusion complexes exist, such as HPßCD, the cluster formation resulting in precipitation is hindered due to the high solubility of CDs in water, resulting in intangible yields to work with even after employing general laboratory recovery methods. Conclusively, histotripsy cavitation experiments successfully showed a decreased cavitation threshold among optimal NCC candidates that were identified, supporting their use in NMH.

Treatment of Metastatic Disease with Immune Checkpoint Inhibitors Nivolumab and Pembrolizumab: Effect of Performance Status on Clinical Outcomes.

Introduction: Although guidelines exist for appropriate use of chemotherapy in the metastatic setting based on performance status, such recommendations are less readily available for immune checkpoint inhibitors (ICIs). We sought to determine whether there is a relationship between Eastern Cooperative Oncology Group (ECOG) performance status and outcomes of immunotherapy in patients treated for metastatic disease at our community-based oncology practice. Methods: Patients (n = 253) were identified as receiving nivolumab or pembrolizumab for stage IV malignancy at Cancer Centers of Colorado, St. Joseph Hospital/SCL Health between June 2018 and November 2020. Patients who initiated therapy after May 2020 were excluded from analysis due to less than 6 months follow-up time. The remaining 183 patients were included in a retrospective cohort study comparing patients with ECOG 0, 1, and 2-4. Sex, age, type of cancer, line of therapy, time on therapy and best response to therapy were determined. These baseline factors and outcomes were compared using analysis of variance (ANOVA) for numeric variables and χ2 tests of association for categorical variables. Time from initiation of ICI to death or hospice was also compared using a log-rank test as well as a multivariate Cox proportional hazards model. Results: Of the 183 patients included, 31.7% had an ECOG of 0, 48.6% an ECOG of 1, and 19.7% an ECOG of 2-4. Non-small cell lung cancer and melanoma represented the majority of patients in each group. Sex and line of therapy did not differ between groups. There was a significant difference in age, with mean age of 62, 66, and 70 in ECOG 0, 1, and 2-4, respectively. Patients (54.6%) remained on therapy for at least 6 months, with no significant difference between groups in ability to complete 6 months of therapy. For ECOG 0, 1, and 2-4, disease control was achieved in 67.2%, 59.6%, and 41.7%, respectively. Analysis of time to death or hospice with a log-rank test showed a significant difference between groups. A multivariate Cox proportional hazards model revealed that patients with ECOG 0 had significantly longer time to death or hospice compared with patients in both other groups after controlling for age, sex, and line of therapy. Conclusion: In this single institution retrospective study of patients receiving nivolumab or pembrolizumab for metastatic cancer, ECOG 0 was associated with disease control and increased time before death or transition to hospice.

What we still don't know about vascularized composite allotransplantation (VCA) outcomes and quality of life measurements.

Vascularized composite allotransplants (VCA) are the only organ transplants purported to be conducted principally to improve quality of life (QOL), rather than to extend or save life - hence they are described as "life-enhancing" (or "life-rescuing"). This is in contrast to "life-extending" solid organ transplantation (SOT). Yet despite more than 20 years of VCA practice (1997-present), little is known about the actual "life-enhancing" impact(s) of VCA on the patient or their families. This article presents an overview of the state of the VCA field and what we still don't know about VCA outcomes, specifically focussing on face and hand transplants as both visible, emotional, and communicative organs. The current measurement of QOL in VCA is insufficient, both conceptually and analytically. It is also, critically, conducted without reference to patient-reported outcomes, or the experiences of family and carers. Drawing on published research in VCA and SOT, as well as preliminary, anecdotal VCA patient interview research, this paper highlights how and why the QOL practices in the field of VCA are not fit for purpose and proposes new ways of analysing QOL. In conclusion, it outlines what needs to happen for the VCA field to move forward positively, and with patients and their families more central to VCA practice and research.

The genetic heterogeneity and drug resistance mechanisms of relapsed refractory multiple myeloma.

Multiple myeloma is the second most common hematological malignancy. Despite significant advances in treatment, relapse is common and carries a poor prognosis. Thus, it is critical to elucidate the genetic factors contributing to disease progression and drug resistance. Here, we carry out integrative clinical sequencing of 511 relapsed, refractory multiple myeloma (RRMM) patients to define the disease's molecular alterations landscape. The NF-κB and RAS/MAPK pathways are more commonly altered than previously reported, with a prevalence of 45-65% each. In the RAS/MAPK pathway, there is a long tail of variants associated with the RASopathies. By comparing our RRMM cases with untreated patients, we identify a diverse set of alterations conferring resistance to three main classes of targeted therapy in 22% of our cohort. Activating mutations in IL6ST are also enriched in RRMM. Taken together, our study serves as a resource for future investigations of RRMM biology and potentially informs clinical management.