Unfavorable social determinants of health and mortality risk by cardiovascular disease status: Findings from a National Study of United States Adults.

BACKGROUND: The association between cumulative burden of unfavorable social determinants of health (SDoH) and all-cause mortality has not been assessed by atherosclerotic cardiovascular disease (ASCVD) status on a population level in the United States. METHODS: We assessed the association between cumulative social disadvantage and all-cause mortality by ASCVD status in the National Health Interview Survey, linked to the National Death Index. RESULTS: In models adjusted for established clinical risk factors, individuals experiencing the highest level of social disadvantage (SDoH-Q4) had over 1.5 (aHR = 1.55; 95%CI = 1.22, 1.96) and 2-fold (aHR = 2.21; 95% CI = 1.91, 2.56) fold increased risk of mortality relative to those with the most favorable social profile (SDoH-Q1), respectively for adults with and without ASCVD; those experiencing co-occurring ASCVD and high social disadvantage had up to four-fold higher risk of mortality (aHR = 3.81; 95%CI = 3.36, 4.32). CONCLUSIONS: These findings emphasize the importance of a healthcare model that prioritizes efforts to identify and address key social and environmental barriers to health and wellbeing, particularly in individuals experiencing the double jeopardy of clinical and social risk.

Long-Duration Neoadjuvant Therapy with FOLFIRINOX Yields Favorable Outcomes for Patients Who Undergo Surgery for Pancreatic Cancer.

BACKGROUND: In 2023 alone, it's estimated that over 64,000 patients will be diagnosed with PDAC and more than 50,000 patients will die of the disease. Current guidelines recommend neoadjuvant therapy for patients with borderline resectable and locally advanced PDAC, and data is emerging on its role in resectable disease. Neoadjuvant chemotherapy may increase the number of patients able to receive complete chemotherapy regimens, increase the rate of microscopically tumor-free resection (R0) margin, and aide in identifying unfavorable tumor biology. To date, this is the largest study to examine surgical outcomes after long-duration neoadjuvant chemotherapy for PDAC. METHODS: Retrospective analysis of single-institution data. RESULTS: The routine use of long-duration therapy in our study (median cycles: FOLFIRINOX = 10; gemcitabine-based = 7) is unique. The majority (85%) of patients received FOLFIRINOX without radiation therapy; the R0 resection rate was 76%. Median OS was 41 months and did not differ significantly among patients with resectable, borderline-resectable, or locally advanced disease. CONCLUSIONS: This study demonstrates that in patients who undergo surgical resection after receipt of long-duration neoadjuvant FOLFIRINOX therapy alone, survival outcomes are similar regardless of pretreatment resectability status and that favorable surgical outcomes can be attained.

Misidentification of the True Aortic Annulus With 2-dimensional Echocardiography: A Critical Appraisal Using 3-Dimensional Imaging.

OBJECTIVES: This study aimed to evaluate the accuracy of identifying the true aortic valve (AV) annulus using 2-dimensional (2D) echocardiography, with the goal of highlighting potential misidentification issues in clinical practice. DESIGN: An observational study employing 3-dimensional (3D) datasets to generate 2D images of the AV annulus for analysis. SETTING: The study was conducted in an academic medical center. PARTICIPANTS: Three-dimensional transesophageal echocardiography datasets were obtained from 11 patients with normal AV and aortic root anatomies undergoing coronary artery bypass surgery. Attending anesthesiologists certified by the National Board of Echocardiography (NBE) were approached subsequently to participate in this study. INTERVENTIONS: Two images per patient were generated from 3D datasets, reflecting the mid-esophageal long-axis view of the AV, a true AV annulus image, and an off-axis image. A survey was distributed to NBE-certified perioperative echocardiographers across 12 academic institutions to identify the true AV annulus from these images. MEASUREMENTS AND MAIN RESULTS: The survey, completed by 45 qualified respondents, revealed a significant misidentification rate of the true AV annulus, with only 36.8% of responses correctly identifying it. The rate of correct identification varied across image sets, with 44.4% of participants unable to correctly identify any true AV annulus image. CONCLUSIONS: The study highlighted the limitations of 2D echocardiography in accurately identifying the true AV annulus in complex 3D structures like the aortic root. The findings suggest a need for greater reliance on advanced imaging modalities, such as 3D echocardiography, to improve accuracy in clinical practice.

Advancing Precision in 3D Echocardiography: Incorporating 3D Markers to Aid Spatial Orientation.

The incorporation of 3D imaging into diagnostic and interventional echocardiography has rapidly expanded in recent years. Applications such as multiplanar reconstruction that were once considered research tools and required off-cart analysis can now readily be performed at the point of image acquisition and in real-time during live image acquisition for procedural guidance. While the application and quality of 3D images have significantly improved in recent years, there remains a noticeable lag in the evolution of artificial intelligence that would further simplify the interpretative processes, both during live sessions and offline analyses. Users are still required to mentally reconstruct sliced images during multiplanar reconstruction based on color-coded planes. While this may be an effortless task for the seasoned echocardiographer, it can be a challenging task for echocardiographers who are less familiar with 3D imaging and multiplanar reconstruction. This article describes the utility of using 3D markers to aid in image interpretation.

Artificial Intelligence for Anesthesiology Board-Style Examination Questions: Role of Large Language Models.

New artificial intelligence tools have been developed that have implications for medical usage. Large language models (LLMs), such as the widely used ChatGPT developed by OpenAI, have not been explored in the context of anesthesiology education. Understanding the reliability of various publicly available LLMs for medical specialties could offer insight into their understanding of the physiology, pharmacology, and practical applications of anesthesiology. An exploratory prospective review was conducted using 3 commercially available LLMs--OpenAI's ChatGPT GPT-3.5 version (GPT-3.5), OpenAI's ChatGPT GPT-4 (GPT-4), and Google's Bard--on questions from a widely used anesthesia board examination review book. Of the 884 eligible questions, the overall correct answer rates were 47.9% for GPT-3.5, 69.4% for GPT-4, and 45.2% for Bard. GPT-4 exhibited significantly higher performance than both GPT-3.5 and Bard (p = 0.001 and p < 0.001, respectively). None of the LLMs met the criteria required to secure American Board of Anesthesiology certification, according to the 70% passing score approximation. GPT-4 significantly outperformed GPT-3.5 and Bard in terms of overall performance, but lacked consistency in providing explanations that aligned with scientific and medical consensus. Although GPT-4 shows promise, current LLMs are not sufficiently advanced to answer anesthesiology board examination questions with passing success. Further iterations and domain-specific training may enhance their utility in medical education.

Synergistic Effect of Nilavembu Choornam-Gold Nanoparticles on Antibiotic-Resistant Bacterial Susceptibility and Contact Lens Contamination-Associated Infectious Pathogenicity.

Antibiotic-resistant bacterial colonies mitigate rapid biofilm formation and have complex cell wall fabrications, making it challenging to penetrate drugs across their biofilm barriers. The objective of this study was to investigate the antibacterial susceptibility of antibiotic-resistant bacteria and contact lens barrenness. Nilavembu Choornam-Gold Nanoparticles (NC-GNPs) were synthesized using NC polyherbal extract and characterized by UV-visible spectrophotometer, SEM-EDX, XRD, Zeta sizer, FTIR, and TEM analysis. Contact lenses with overnight cultures of antibiotic-resistant bacteria K. pneumoniae and S. aureus showed significant differences in growth, biofilm formation, and infection pathogenicity. The NC-GNPs were observed in terms of size (average size is 57.6 nm) and surface chemistry. A zone of inhibition was calculated for K. pneumoniae 18.8 ± 1.06, S. aureus 23.6 ± 1.15, P. aeruginosa 24.16 ± 0.87, and E. faecalis 24.5 ± 1.54 mm at 24 h of NC-GNPs alone treatment. In electron microscopy studies, NC-GNP-treated groups showed nuclear shrinkage, nuclear disintegration, degeneration of cell walls, and inhibited chromosomal division. In contrast, normal bacterial colonies had a higher number of cell divisions and routinely migrated toward cell multiplications. NC-GNPs exhibited antibacterial efficacy against antibiotic-resistant bacteria when compared to NC extract alone. We suggest that NC-GNPs are highly valuable to the population of hospitalized patients and other people to reduce the primary complications of contact lens contamination-oriented microbial infection and the therapeutic efficiency of antibiotic-resistant bacterial pathogenicity.

An International Expert Delphi Consensus on Defining Textbook Outcome in Liver Surgery (TOLS).

OBJECTIVE: To reach global expert consensus on the definition of TOLS in minimally invasive and open liver resection among renowned international expert liver surgeons using a modified Delphi method. BACKGROUND: Textbook outcome is a novel composite measure combining the most desirable postoperative outcomes into one single measure and representing the ideal postoperative course. Despite a recently developed international definition of Textbook Outcome in Liver Surgery (TOLS), a standardized and expert consensus-based definition is lacking. METHODS: This international, consensus-based, qualitative study used a Delphi process to achieve consensus on the definition of TOLS. The survey comprised 6 surgical domains with a total of 26 questions on individual surgical outcome variables. The process included 4 rounds of online questionnaires. Consensus was achieved when a threshold of at least 80% agreement was reached. The results from the Delphi rounds were used to establish an international definition of TOLS. RESULTS: In total, 44 expert liver surgeons from 22 countries and all 3 major international hepato-pancreato-biliary associations completed round 1. Forty-two (96%), 41 (98%), and 41 (98%) of the experts participated in round 2, 3, and 4, respectively. The TOLS definition derived from the consensus process included the absence of intraoperative grade ≥2 incidents, postoperative bile leakage grade B/C, postoperative liver failure grade B/C, 90-day major postoperative complications, 90-day readmission due to surgery-related major complications, 90-day/in-hospital mortality, and the presence of R0 resection margin. CONCLUSIONS: This is the first study providing an international expert consensus-based definition of TOLS for minimally invasive and open liver resections by the use of a formal Delphi consensus approach. TOLS may be useful in assessing patient-level hospital performance and carrying out international comparisons between centers with different clinical practices to further improve patient outcomes.

The political and social contexts of global road safety: challenges for the next decade.

The goal of this Series paper is to show how road safety has evolved as a global public health issue over the past two decades and to discuss the political and economic dynamics that led to this change. Specifically, the key stakeholders, influences, networks, issue framing, actor power, and synergistic interactions that have contributed to how road safety has evolved as a global public health issue will be discussed. In doing so, we capture the important chronology of events and discuss a set of challenges that highlight the complexity of road safety. We posit that the global road safety community needs to re-evaluate its role and strategy for the next decade and focus more on implementation and country action to achieve reductions in road traffic injuries. We call for an open and inclusive process to ensure that such a reflection occurs before the end of the current decade.

Improvement in trauma care for road traffic injuries: an assessment of the effect on mortality in low-income and middle-income countries.

Over 90% of the annual 1·35 million worldwide deaths due to road traffic injuries (RTIs) occur in low-income and middle-income countries (LMICs). For this Series paper, our aim was two-fold. Firstly, to review evidence on effective interventions for victims of RTIs; and secondly, to estimate the potential number of lives saved by effective trauma care systems and clinical interventions in LMICs. We reviewed all the literature on trauma-related health systems and clinical interventions published during the past 20 years using MEDLINE, Embase, and Web of Science. We included studies in which mortality was the primary outcome and excluded studies in which trauma other than RTIs was the predominant injury. We used data from the Global Status Report on Road Safety 2018 and a Monte Carlo simulation technique to estimate the potential annual attributable number of lives saved in LMICs. Of the 1921 studies identified for our review of the literature, 62 (3·2%) met the inclusion criteria. Only 28 (1·5%) had data to calculate relative risk. We found that more than 200 000 lives per year can be saved globally with the implementation of a complete trauma system with 100% coverage in LMICs. Partial system improvements such as establishing trauma centres (>145 000 lives saved) and instituting and improving trauma teams (>115 000) were also effective. Emergency medical services had a wide range of effects on mortality, from increasing mortality to saving lives (>200 000 excess deaths to >200 000 lives saved per year). For clinical interventions, damage control resuscitation (>60 000 lives saved per year) and institution of interventional radiology (>50 000 lives saved per year) were the most effective interventions. On the basis of the scarce evidence available, a few key interventions have been identified to provide guidance to policy makers and clinicians on evidence-based interventions that can reduce deaths due to RTIs in LMICs. We also highlight important gaps in knowledge on the effects of other interventions.

Saving lives through road safety risk factor interventions: global and national estimates.

Global road mortality is a leading cause of death in many low-income and middle-income countries. Data to support priority setting under current resource constraints are urgently needed to achieve Sustainable Development Goal (SDG) 3.6. This Series paper estimates the potential number of lives saved if each country implemented interventions to address risk factors for road injuries. We did a systematic review of all available evidence-based, preventive interventions for mortality reduction that targeted the four main risk factors for road injuries (ie, speeding, drink driving, helmet use, and use of seatbelt or child restraint). We used literature review variables and considered three key country-level variables (gross domestic product per capita, population density, and government effectiveness) to generate country-specific estimates on the potential annual attributable number of lives that would be saved by interventions focusing on these four risk factors in 185 countries. Our results suggest that the implementation of evidence-based road safety interventions that target the four main road safety risk factors could prevent between 25% and 40% of all fatal road injuries worldwide. Interventions addressing speed could save about 347 258 lives globally per year, and at least 16 304 lives would be saved through drink driving interventions. The implementation of seatbelt interventions could save about 121 083 lives, and 51 698 lives could be saved by helmet interventions. We identify country-specific estimates of the potential number of lives saved that would be attributable to these interventions. Our results show the potential effectiveness of the implementation and scaling of these interventions. This paper presents key evidence for priority setting on road safety interventions and shows a path for reaching SDG 3.6.

Benefits of EUS-guided gastroenterostomy over surgical gastrojejunostomy in the palliation of malignant gastric outlet obstruction: a large multicenter experience.

BACKGROUND AND AIMS: Palliation of malignant gastric outlet obstruction (mGOO) allows resumption of peroral intake. Although surgical gastrojejunostomy (SGJ) provides durable relief, it may be associated with a higher morbidity, interfere with chemotherapy, and require an optimum nutritional status. EUS-guided gastroenterostomy (EUS-GE) has emerged as a minimally invasive alternative. We aimed to conduct the largest comparative series to date between EUS-GE and SGJ for mGOO. METHODS: This multicenter retrospective study included consecutive patients undergoing SGJ or EUS-GE at 6 centers. Primary outcomes included time to resumption of oral intake, length of stay (LOS), and mortality. Secondary outcomes included technical and clinical success, reintervention rates, adverse events (AEs), and resumption of chemotherapy. RESULTS: A total of 310 patients were included (EUS-GE, n = 187; SGJ, n = 123). EUS-GE exhibited significantly lower time to resumption of oral intake (1.40 vs 4.06 days, P < .001), at lower albumin levels (2.95 vs 3.33 g/dL, P < .001), and a shorter LOS (5.31 vs 8.54 days, P < .001) compared with SGJ; there was no difference in mortality (48.1% vs 50.4%, P = .78). Technical (97.9% and 100%) and clinical (94.1% vs 94.3%) success was similar in the EUS-GE and SGJ groups, respectively. EUS-GE had lower rates of AEs (13.4% vs 33.3%, P < .001) but higher reintervention rates (15.5% vs 1.63%, P < .001). EUS-GE patients exhibited significantly lower interval time to resumption of chemotherapy (16.6 vs 37.8 days, P < .001). Outcomes between the EUS-GE and laparoscopic (n = 46) surgical approach showed that EUS-GE had shorter interval time to initiation/resumption of oral intake (3.49 vs 1.46 days, P < .001), decreased LOS (9 vs 5.31 days, P < .001), and a lower rate of AEs (11.9% vs 17.9%, P = .003). CONCLUSIONS: This is the largest study to date showing that EUS-GE can be performed among nutritionally deficient patients without affecting the technical and clinical success compared with SGJ. EUS-GE is associated with fewer AEs while allowing earlier resumption of diet and chemotherapy.

Engineered Microencapsulated Lactoferrin Nanoconjugates for Oral Targeted Treatment of Colon Cancer.

Despite current progress in the development of targeted therapies for cancer treatment, there is a lack in convenient therapeutics for colorectal cancer (CRC). Lactoferrin nanoparticles (Lf NPs) are a promising drug delivery system in cancer therapy. However, numerous obstacles impede their oral delivery, including instability against stomach enzymes and premature uptake during passage through the small intestine. Microencapsulation of Lf NPs offer a great solution for these obstacles. It can protect Lf NPs and their drug payloads from degradation in the upper gastrointestinal tract (GIT), reduce burst drug release, and improve the release profile of the encapsulated NPs triggered by stimuli in the colon. Here, we developed nanoparticle-in-microparticle delivery systems (NIMDs) for the oral delivery of docetaxel (DTX) and atorvastatin (ATR). The NPs were obtained by dual conjugation of DTX and ATR into the Lf backbone, which was further microencapsulated into calcium-crosslinked microparticles using polysaccharide-protein hybrid copolymers. The NIMDs showed no detectable drug release in the upper GIT compared to NPs. Furthermore, sustained release of the NPs from the NIMDs in rat cecal content was observed. Moreover, the in vivo study demonstrated the superiority of the NIMDs over NPs in CRC treatment by suppressing p-AKT, p-ERK1/2, and NF-κB. This study provides the proof of concept for using NIMDs to enhance the effect of protein NPs in CRC treatment.

Cumulative social disadvantage and health-related quality of life: national health interview survey 2013-2017.

BACKGROUND: Evidence for the association between social determinants of health (SDoH) and health-related quality of life (HRQoL) is largely based on single SDoH measures, with limited evaluation of cumulative social disadvantage. We examined the association between cumulative social disadvantage and the Health and Activity Limitation Index (HALex). METHODS: Using adult data from the National Health Interview Survey (2013-2017), we created a cumulative disadvantage index by aggregating 47 deprivations across 6 SDoH domains. Respondents were ranked using cumulative SDoH index quartiles (SDoH-Q1 to Q4), with higher quartile groups being more disadvantaged. We used two-part models for continuous HALex scores and logistic regression for poor HALex (< 20th percentile score) to examine HALex differences associated with cumulative disadvantage. Lower HALex scores implied poorer HRQoL performance. RESULTS: The study sample included 156,182 respondents, representing 232.8 million adults in the United States (mean age 46 years; 51.7% women). The mean HALex score was 0.85 and 17.7% had poor HALex. Higher SDoH quartile groups had poorer HALex performance (lower scores and increased prevalence of poor HALex). A unit increase in SDoH index was associated with - 0.010 (95% CI [-0.011, -0.010]) difference in HALex score and 20% higher odds of poor HALex (odds ratio, OR = 1.20; 95% CI [1.19, 1.21]). Relative to SDoH-Q1, SDoH-Q4 was associated with HALex score difference of -0.086 (95% CI [-0.089, -0.083]) and OR = 5.32 (95% CI [4.97, 5.70]) for poor HALex. Despite a higher burden of cumulative social disadvantage, Hispanics had a weaker SDoH-HALex association than their non-Hispanic White counterparts. CONCLUSIONS: Cumulative social disadvantage was associated with poorer HALex performance in an incremental fashion. Innovations to incorporate SDoH-screening tools into clinical decision systems must continue in order to accurately identify socially vulnerable groups in need of both clinical risk mitigation and social support. To maximize health returns, policies can be tailored through community partnerships to address systemic barriers that exist within distinct sociodemographic groups, as well as demographic differences in health perception and healthcare experience.

National cervical cancer burden estimation through systematic review and analysis of publicly available data in Pakistan.

BACKGROUND: Cervical cancer is a major cause of cancer-related deaths among women worldwide. Paucity of data on cervical cancer burden in countries like Pakistan hamper requisite resource allocation. OBJECTIVE: To estimate the burden of cervical cancer in Pakistan using available data sources. METHODS: We performed a systematic review to identify relevant data on Pakistan between 1995 to 2022. Study data identified through the systematic review that provided enough information to allow age specific incidence rates and age standardized incidence rates (ASIR) calculations for cervical cancer were merged. Population at risk estimates were derived and adjusted for important variables in the care-seeking pathway. The calculated ASIRs were applied to 2020 population estimates to estimate the number of cervical cancer cases in Pakistan. RESULTS: A total of 13 studies reported ASIRs for cervical cancer for Pakistan. Among the studies selected, the Karachi Cancer Registry reported the highest disease burden estimates for all reported time periods: 1995-1997 ASIR = 6.81, 1998-2002 ASIR = 7.47, and 2017-2019 ASIR = 6.02 per 100,000 women. Using data from Karachi, Punjab and Pakistan Atomic Energy Cancer Registries from 2015-2019, we derived an unadjusted ASIR for cervical cancer of 4.16 per 100,000 women (95% UI 3.28, 5.28). Varying model assumptions produced adjusted ASIRs ranging from 5.2 to 8.4 per 100,000 women. We derived an adjusted ASIR of 7.60, (95% UI 5.98, 10.01) and estimated 6166 (95% UI 4833, 8305) new cases of cervical cancer per year. CONCLUSION: The estimated cervical cancer burden in Pakistan is higher than the WHO target. Estimates are sensitive to health seeking behavior, and appropriate physician diagnostic intervention, factors that are relevant to the case of cervical cancer, a stigmatized disease in a low-lower middle income country setting. These estimates make the case for approaching cervical cancer elimination through a multi-pronged strategy.

Low educational attainment is associated with higher all-cause and cardiovascular mortality in the United States adult population.

INTRODUCTION: Educational attainment is an important social determinant of health (SDOH) for cardiovascular disease (CVD). However, the association between educational attainment and all-cause and CVD mortality has not been longitudinally evaluated on a population-level in the US, especially in individuals with atherosclerotic cardiovascular disease (ASCVD). In this nationally representative study, we assessed the association between educational attainment and the risk of all-cause and cardiovascular (CVD) mortality in the general adult population and in adults with ASCVD in the US. METHODS: We used data from the 2006-2014 National Death Index-linked National Health Interview Survey for adults ≥ 18 years. We generated age-adjusted mortality rates (AAMR) by levels of educational attainment (< high school (HS), HS/General Education Development (GED), some college, and ≥ College) in the overall population and in adults with ASCVD. Cox proportional hazards models were used to examine the multivariable-adjusted associations between educational attainment and all-cause and CVD mortality. RESULTS: The sample comprised 210,853 participants (mean age 46.3), representing ~ 189 million adults annually, of which 8% had ASCVD. Overall, 14.7%, 27%, 20.3%, and 38% of the population had educational attainment < HS, HS/GED, Some College, and ≥ College, respectively. During a median follow-up of 4.5 years, all-cause age-adjusted mortality rates were 400.6 vs. 208.6 and 1446.7 vs. 984.0 for the total and ASCVD populations for < HS vs ≥ College education, respectively. CVD age adjusted mortality rates were 82.1 vs. 38.7 and 456.4 vs 279.5 for the total and ASCVD populations for < HS vs ≥ College education, respectively. In models adjusting for demographics and SDOH, < HS (reference = ≥ College) was associated with 40-50% increased risk of mortality in the total population and 20-40% increased risk of mortality in the ASCVD population, for both all-cause and CVD mortality. Further adjustment for traditional risk factors attenuated the associations but remained statistically significant for < HS in the overall population. Similar trends were seen across sociodemographic subgroups including age, sex, race/ethnicity, income, and insurance status. CONCLUSIONS: Lower educational attainment is independently associated with increased risk of all-cause and CVD mortality in both the total and ASCVD populations, with the highest risk observed for individuals with < HS education. Future efforts to understand persistent disparities in CVD and all-cause mortality should pay close attention to the role of education, and include educational attainment as an independent predictor in mortality risk prediction algorithms.

Spiro heterocycles bearing piperidine moiety as potential scaffold for antileishmanial activity: synthesis, biological evaluation, and in silico studies.

New spiro-piperidine derivatives were synthesised via the eco-friendly ionic liquids in a one-pot fashion. The in vitro antileishmanial activity against Leishmania major promastigote and amastigote forms highlighted promising antileishmanial activity for most of the derivatives, with superior activity compared to miltefosine. The most active compounds 8a and 9a exhibited sub-micromolar range of activity, with IC50 values of 0.89 µM and 0.50 µM, respectively, compared to 8.08 µM of miltefosine. Furthermore, the antileishmanial activity reversal of these compounds via folic and folinic acids displayed comparable results to the positive control trimethoprim. This emphasises that their antileishmanial activity is through the antifolate mechanism via targeting DHFR and PTR1. The most active compounds showed superior selectivity and safety profile compared to miltefosine against VERO cells. Moreover, the docking experiments of 8a and 9a against Lm-PTR1 rationalised the observed in vitro activities. Molecular dynamics simulations confirmed a stable and high potential binding to Lm-PTR1.

Virtual Reality: The Future of Invasive Procedure Training?

Invasive procedures are associated with adverse events that are both hazardous to patients and expensive to treat. A trainee is expected to perform complex sterile invasive procedures in a dynamic environment under time pressure while maintaining patient safety at the highest standard of care. For mastery in performing an invasive procedure, the automatism of the technical aspects is required, as well as the ability to adapt to patient conditions, anatomic variability, and environmental stressors. Virtual reality (VR) simulation training is an immersive technology with immense potential for medical training, potentially enhancing clinical proficiency and improving patient safety. Virtual reality can project near-realistic environments onto a head-mounted display, allowing users to simulate and interact with various scenarios. Virtual reality has been used extensively for task training in various healthcare-related disciplines and other fields, such as the military. These scenarios often incorporate haptic feedback for the simulation of physical touch and audio and visual stimuli. In this manuscript, the authors have presented a historical review, the current status, and the potential application of VR simulation training for invasive procedures. They specifically explore a VR training module for central venous access as a prototype for invasive procedure training to describe the advantages and limitations of this evolving technology.

Timing of Blood Transfusions and 30-Day Patient Outcomes After Coronary Artery Bypass Graft Surgery.

OBJECTIVE: Packed red blood cell transfusion during coronary artery bypass graft surgery is known to be associated with adverse outcomes. However, the association of the timing between transfusions in relation to discharge and 30-day postoperative outcomes has not been studied. The study authors investigated the impact of transfusion timing on 30-day surgical outcomes. DESIGN: A retrospective review. SETTING: At a single tertiary-care academic hospital. PARTICIPANTS: A total of 2,481 adult patients underwent primary coronary artery bypass graft surgery between January 2014 and December 2020. MEASUREMENTS AND MAIN RESULTS: The relationship between the timing of packed red blood cell transfusion (intraoperative, postoperative, or both) and 30-day postoperative outcome variables was calculated as an odds ratio. The influence of timing of transfusion on adjusted probability of postoperative complications was plotted against the lowest intraoperative hematocrit. The median age of the population was 67 years (60.0-74.0), body mass index was 28.5 (25.6-32.3) kg/m2, and 497 (20.0%) were female. A total of 1,588 (36%) patients received packed red blood cell transfusions; 182 (7.3%) received intraoperative transfusions, 489 (19.7%) received postoperative transfusions, and 222 (9.0%) received both (intraoperative and postoperative transfusions). Postoperative transfusion was associated with significantly higher odds of readmission (1.83 [1.32-2.54], p = 0.002) and heart failure (1.64 [1.2-2.23], p = 0.008) compared to patients with no transfusions; whereas intraoperative transfusions were not. CONCLUSION: The authors' data suggested that the postoperative timing of transfusion in patients undergoing coronary artery bypass graft surgery may be associated with an increased incidence of 30-day heart failure and readmission. Prospective research is needed to conclusively confirm these findings.

Development and Validation of a Rapid LC-MS/MS Method for Quantifying Alvocidib: In Silico and In Vitro Metabolic Stability Estimation in Human Liver Microsomes.

Alvocidib (AVC; flavopiridol) is a potent cyclin-dependent kinase inhibitor used in patients with acute myeloid leukemia (AML). The FDA has approved orphan drug designation to AVC for treating patients with AML. In the current work, the in silico calculation of AVC metabolic lability was done using the P450 metabolism module of the StarDrop software package, that is expressed as a composite site lability (CSL). This was followed by establishing an LC-MS/MS analytical method for AVC estimation in human liver microsomes (HLMs) to assess metabolic stability. AVC and glasdegib (GSB), used as internal standards (IS), were separated utilizing a C18 column (reversed chromatography) with an isocratic mobile phase. The lower limit of quantification (LLOQ) was 5.0 ng/mL, revealing the sensitivity of the established LC-MS/MS analytical method that exhibited a linearity in the range 5-500 ng/mL in the HLMs matrix with correlation coefficient (R2 = 0.9995). The interday and intraday accuracy and precision of the established LC-MS/MS analytical method were -1.4% to 6.7% and -0.8% to 6.4%, respectively, confirming the reproducibility of the LC-MS/MS analytical method. The calculated metabolic stability parameters were intrinsic clearance (CLint) and in vitro half-life (t1/2) of AVC at 26.9 µL/min/mg and 25.8 min, respectively. The in silico results from the P450 metabolism model matched the results generated from in vitro metabolic incubations; therefore, the in silico software can be used to predict the metabolic stability of the drugs, saving time and resources. AVC exhibits a moderate extraction ratio, indicating reasonable in vivo bioavailability. The established chromatographic methodology was the first LC-MS/MS method designed for AVC estimation in HLMs matrix that was applied for AVC metabolic stability estimation.

Development of an LC-MS/MS Method for Quantification of Sapitinib in Human Liver Microsomes: In Silico and In Vitro Metabolic Stability Evaluation.

Sapitinib (AZD8931, SPT) is a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) family (pan-erbB). In multiple tumor cell lines, STP has been shown to be a much more potent inhibitor of EGF-driven cellular proliferation than gefitinib. In the current study, a highly sensitive, rapid, and specific LC-MS/MS analytical method for the estimation of SPT in human liver microsomes (HLMs) was established with application to metabolic stability assessment. The LC-MS/MS analytical method was validated in terms of linearity, selectivity, precision, accuracy, matrix effect, extraction recovery, carryover, and stability following the FDA guidelines for bioanalytical method validation. SPT was detected using electrospray ionization (ESI) as an ionization source under multiple reaction monitoring (MRM) in the positive ion mode. The IS-normalized matrix factor and extraction recovery were acceptable for the bioanalysis of SPT. The SPT calibration curve was linear, from 1 ng/mL to 3000 ng/mL HLM matrix samples, with a linear regression equation of y = 1.7298x + 3.62941 (r2 = 0.9949). The intraday and interday accuracy and precision values of the LC-MS/MS method were -1.45-7.25% and 0.29-6.31%, respectively. SPT and filgotinib (FGT) (internal standard; IS) were separated through the use of an isocratic mobile phase system with a Luna 3 µm PFP(2) column (150 × 4.6 mm) stationary phase column. The limit of quantification (LOQ) was 0.88 ng/mL, confirming the LC-MS/MS method sensitivity. The intrinsic clearance and in vitro half-life of STP were 38.48 mL/min/kg and 21.07 min, respectively. STP exhibited a moderate extraction ratio that revealed good bioavailability. The literature review demonstrated that the current analytical method is the first developed LC-MS/MS method for the quantification of SPT in an HLM matrix with application to SPT metabolic stability evaluation.