Search

Sunny J Patel,1 Lakshmi Pappoppula,2 Achuta K Guddati2 1Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA; 2Division of Hematology/Oncology, Georgia Cancer Center, Augusta University, Augusta, GA, 30912, USACorrespondence: Achuta K GuddatiDivision of Hematology/Oncology, Georgia Cancer Center, Augusta University, Augusta, GA, 30909, USATel +1 312-404-8928Email aguddati@augusta.eduBackground: The clinical course of soft tissue sarcomas is often dependent on the grade of the tumor. The variability of incidence-based mortality in low-grade and high-grade soft tissue sarcomas (STS) with respect to gender and race over the past decade has not been well studied. This study analyzes the rates of incidence-based mortality from the years 2000 to 2016 amongst the grades, genders and racial groups of patients with STS.Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried to conduct a nation-wide analysis for the years 2000 to 2016. Incidence-based mortality for all stages of low-grade and high-grade soft tissue sarcomas was queried and the results were grouped by race (Caucasian/White vs African American/Black) and gender. All stages and ages were included in the analysis and trend from 2000 to 2016 was analyzed.Results: The incidence-based mortality rates for Caucasians are similar to African Americans in both grades and genders. Rates were not analyzed for American Indian and Asian/Pacific Islanders due to small sample size. Mortality rates of high-grade soft tissue sarcomas were significantly higher compared to low-grade tumors. A higher rate of mortality is noted in Caucasian males compared to African Americans males despite past observations of higher incidence in African Americans. There was no significant change in the rate when trended over the past decade (2007 to 2016).Conclusion: This study highlights the higher rate of incidence-based mortality in Caucasian males compared to African American males in the past 15 years despite a lower incidence reported in the 1995 to 2008 period. With no significant change in mortality rates/year noted during this time period, this study implies that soft tissue sarcomas in Caucasian males have worse outcomes. Further research is needed to understand the mechanism underlying this disparity.Keywords: soft tissue sarcoma, incidence-based mortality, disparity

Sejal J Patel,1 Kathi J Kemper,2 Joseph P Kitzmiller3 1College of Public Health, The Ohio State University, 2Center for Integrative Health and Wellness, The Ohio State Wexner University Medical Center, 3Department of Biological Chemistry and Pharmacology, College of Medicine, The Ohio State University, Columbus, OH, USA Abstract: Over recent decades, the demand for complementary and alternative medicine (CAM) has continued to rise in the US. Like the practice of traditional Western medicine, CAM is associated with not only significant health benefits but also significant risks. Unlike traditional Western medicine, however, much of CAM use is less regulated and often occurs unbeknownst to a patient’s medical doctor. The use of herbals, dietary supplements, and over-the-counter (OTC) medications can result in adverse effects, and many significant interactions can occur when their use is combined with allopathic medications. Even the more peripheral CAM practices (eg, acupuncture, massage, yoga, and Reiki) have associated risk (eg, adverse effects or worsening of physical injury and conditions). There is, however, impetus for change: both patients and physicians favor increasing physician knowledge of CAM and the synergistic implementation of CAM into routine clinical practice. Although improvement has been achieved from contemporary physician educational efforts, recently published results from patient and physician surveys strongly indicate that additional effort to increase physician knowledge of CAM is needed. Utilizing a 37-item survey and convenience-sampling methodology, we collected detailed information from 114 physicians, fellows, and residents from the Ohio State University Medical Center regarding impediments to increasing physician knowledge of CAM and its implementation in routine clinical practice. The aggregate results of our survey data showed that most physicians 1) desired to increase their knowledge of CAM, 2) believed that less than half of their patients were spontaneously reporting their use of CAM therapies, 3) were not aware of available evidence-based resources on CAM, 4) preferred case-based lectures for learning about CAM, and 5) reported insufficient time during patient encounters as the primary barrier for increasing the implementation of CAM in routine clinical practice. Keywords: attitudes, integrative medicine, survey, holistic medicine, clinical practice

Kathryn M Spiekerman,1 Sameer J Patel,2,3 Rupal Patel,4 Larry K Kociolek,2,3 1School of Public Health, University of Illinois at Chicago, 2Division of Pediatric Infectious Diseases, Ann & Robert H. Lurie Children’s Hospital of Chicago, 3Department of Pediatrics, Northwestern University Feinberg School of Medicine, 4Department of Pharmacy, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA Abstract: Despite the enormous volume of antibiotics prescribed by pediatricians, resources to promote judicious antibiotic use are primarily limited to hospitals. The primary objective of this survey was to delineate the availability, characteristics, and perceptions of antibiograms among pediatricians. As a secondary objective, we sought to delineate the availability of other infectious diseases (ID)-related educational resources among pediatricians, the perceived need for additional resources, and their general educational preferences. We developed an anonymous electronic survey using the Research Electronic Data Capture tool, and it was sent via email to all members of the Illinois Chapter of the American Academy of Pediatrics (ICAAP). Participants were excluded if they had not completed pediatrics residency or if they had not prescribed antibiotics in the past month. Of the 1,825 ICAAP members, 294 (16%) responded; of these, 239 (81%) were eligible and completed the survey. Of the 239 respondents, 139 (58%) had access to an antibiogram and 60 (25%) had access to a pediatric-specific antibiogram. Access to a pediatric-specific antibiogram was associated with subspecialty training (P=0.007) and practice location in Chicago (P

BackgroundConcerns have been raised about the utility of self-report assessments in predicting future suicide attempts. Clinicians in pediatric emergency departments (EDs) often are required to assess suicidal risk. The Death Implicit Association Test (IAT) is an alternative to self-report assessment of suicidal risk that may have utility in ED settings.MethodsA total of 1679 adolescents recruited from 13 pediatric emergency rooms in the Pediatric Emergency Care Applied Research Network were assessed using a self-report survey of risk and protective factors for a suicide attempt, and the IAT, and then followed up 3 months later to determine if an attempt had occurred. The accuracy of prediction was compared between self-reports and the IAT using the area under the curve (AUC) with respect to receiver operator characteristics.ResultsA few self-report variables, namely, current and past suicide ideation, past suicidal behavior, total negative life events, and school or social connectedness, predicted an attempt at 3 months with an AUC of 0.87 [95% confidence interval (CI), 0.84-0.90] in the entire sample, and AUC = 0.91, (95% CI 0.85-0.95) for those who presented without reported suicidal ideation. The IAT did not add significantly to the predictive power of selected self-report variables. The IAT alone was modestly predictive of 3-month attempts in the overall sample ((AUC = 0.59, 95% CI 0.52-0.65) and was a better predictor in patients who were non-suicidal at baseline (AUC = 0.67, 95% CI 0.55-0.79).ConclusionsIn pediatric EDs, a small set of self-reported items predicted suicide attempts within 3 months more accurately than did the IAT.

The discovery of topological insulators, materials with bulk band gaps and protected cross-gap surface states in compounds such as Bi2Se3, has generated much interest in identifying topological surface states (TSSs) in other classes of materials. In particular, recent theoretical calculations suggest that TSSs may be found in half-Heusler ternary compounds. If experimentally realizable, this would provide a materials platform for entirely new heterostructure spintronic devices that make use of the structurally identical but electronically varied nature of Heusler compounds. Here we show the presence of a TSS in epitaxially grown thin films of the half-Heusler compound PtLuSb. Spin- and angle-resolved photoemission spectroscopy, complemented by theoretical calculations, reveals a surface state with linear dispersion and a helical tangential spin texture consistent with previous predictions. This experimental verification of topological behaviour is a significant step forward in establishing half-Heusler compounds as a viable material system for future spintronic devices.

Rheumatoid arthritis, juvenile rheumatoid arthritis, Sjögren's syndrome, the seronegative spondyloarthropathies, systemic lupus erythematosus, multiple sclerosis, giant cell arteritis, and Graves' disease are autoimmune disorders commonly encountered by family physicians. These autoimmune disorders can have devastating systemic and ocular effects. Ocular symptoms may include dry or red eyes, foreign-body sensation, pruritus, photophobia, pain, visual changes, and even complete loss of vision. Because a number of these diseases may initially present with ocular symptoms, physicians should maintain a high index of suspicion to make a timely diagnosis. A thorough ophthalmic examination, including visual acuity, pupillary reaction, ocular motility, confrontation field testing, external inspection, and direct ophthalmoscopy with fluorescein staining, should be completed. In the patient with the complaint of a 'dry eye' or a 'red eye,' simple tools such as the Schirmer's test or the blanching effect of phenylephrine can be useful in diagnosis. In general, managing the systemic effects with nonsteroidal anti-inflammatory drugs, corticosteroids, and immunosuppressive agents controls the ocular symptoms. When visual function is threatened, surgical therapy may be necessary. Early and accurate diagnosis with prompt treatment or referral to an ophthalmologist may prevent systemic and ocular disabilities. [ABSTRACT FROM AUTHOR]

Cell state dynamics underlying successful tissue regeneration are undercharacterized. In the intestine, damage prompts epithelial reprogramming into revival stem cells (revSCs) that reconstitute Lgr5 + intestinal stem cells (ISCs). Here single-nuclear multi-omics of mouse crypts regenerating from irradiation shows revSC chromatin accessibility overlaps with ISCs and differentiated lineages. While revSC genes themselves are accessible throughout homeostatic epithelia, damage-induced remodelling of chromatin in the crypt converges on Hippo and the transforming growth factor-beta (TGFβ) signalling pathway, which we show is transiently activated and directly induces functional revSCs. Combinatorial gene expression analysis further suggests multiple sources of revSCs, and we demonstrate TGFβ can reprogramme enterocytes, goblet and paneth cells into revSCs and show individual revSCs form organoids. Despite this, loss of TGFβ signalling yields mild regenerative defects, whereas interference in both Hippo and TGFβ leads to profound defects and death. Intestinal regeneration is thus poised for activation by a compensatory system of crypt-localized, transient morphogen cues that support epithelial reprogramming and robust intestinal repair., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: For extended-release drug formulations, effective half-life (t1/2eff) is a relevant pharmacokinetic parameter to inform dosing strategies and time to reach steady state. Tacrolimus, an immunosuppressant commonly used for the prophylaxis of organ rejection in transplant patients, is available as both immediate- and extended-release formulations. To the best of our knowledge, the t1/2eff of tacrolimus from these different formulations has not yet been assessed. The objective of this study was to characterize the t1/2eff and terminal half-life (t1/2z) of an extended-release once-daily tacrolimus formulation (LCPT) and twice-daily immediate-release tacrolimus (IR-Tac)., Methods: A noncompartmental analysis of pharmacokinetic data obtained from a phase 2 study in de novo kidney transplant recipients receiving either LCPT or IR-Tac was conducted. Intensive blood sampling was performed on days 1, 7, and 14, and tacrolimus whole blood concentrations were measured using a validated liquid chromatography with tandem mass spectrometry method. T1/2eff was estimated using within-participant accumulation ratios. T1/2z was estimated by linear regression of the terminal phase of the concentration versus time profile., Results: The median accumulation ratios of LCPT and IR-Tac on day 14 were 3.18 and 2.06, respectively.The median (interquartile range; IQR) t1/2eff for LCPT at day 14 of dosing was 48.4 (37.4-77.9) hours, whereas the t1/2z was 20.3 (17.6-22.9) hours. For IR-Tac, the median (IQR) t1/2eff and t1/2z on day 14 were 12.5 (8.8-23.0) hours and 12.2 (9.2-15.7) hours, respectively., Conclusions: Consistent with its prolonged release of tacrolimus, LCPT demonstrated a higher accumulation ratio and a longer t1/2eff compared with IR-Tac. These findings underscore the pharmacokinetic differences between different drug formulations of the same moiety and may help inform dose adjustments for LCPT in kidney transplantation., Competing Interests: J.D. Momper has received consulting fees from Veloxis Pharmaceuticals, Inc. B.M. Masters and S.J. Patel are employees of Veloxis Pharmaceuticals, Inc. R. Venkataramanan, A.S. Jantz, D.M. Cibrik, and K. Birdwell have no conflicts of interest to declare., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.)

The clinical outcome of patients with muscle-invasive bladder cancer (MIBC) is poor despite the approval of neoadjuvant chemotherapy or immunotherapy to improve overall survival after cystectomy. MIBC subtypes, immune, transcriptome, metabolomic signatures, and mutation burden have the potential to predict treatment response but none have been incorporated into clinical practice, as tumor heterogeneity and lineage plasticity influence their efficacy. Using the PRISMA statement, we conducted a systematic review of the literature, involving 135 studies published within the last five years, to identify studies reporting on the prognostic value of protein-based biomarkers for response to neoadjuvant therapy in patients with MIBC. The studies were grouped based on biomarkers related to molecular subtypes, cancer stem cell, actin-cytoskeleton, epithelial-mesenchymal transition, apoptosis, and tumor-infiltrating immune cells. These studies show the potential of protein-based biomarkers, especially in the spatial context, to reduce the influence of tumor heterogeneity on a biomarker's prognostic capability. Nevertheless, currently, there is little consensus on the methodology, reagents, and the scoring systems to allow reliable assessment of the biomarkers of interest. Furthermore, the small sample size of several studies necessitates the validation of potential prognostic biomarkers in larger multicenter cohorts before their use for individualizing neoadjuvant therapy regimens for patients with MIBC.

Background: Regional citrate anticoagulation (RCA) has emerged as a treatment modality that reduces bleeding risk and filter clotting. With initial experience of using RCA with continuous renal replacement therapy (CRRT), we have formulated a working protocol based on published literature., Objective: The study aimed to evaluate the protocol for routine use of RCA during CRRT requiring anticoagulation and evaluation of filter life., Methodology: It is a single-center, open-label, prospective, non-randomized, non-interventional, single-arm, observational study conducted at a tertiary care hospital between September 2022 and July 2023. All adult patients with acute kidney injury (AKI) or hyperammonemia requiring CRRT and necessitating the use of anticoagulation were enrolled in the study. The study used Prisma Flex M100 AN 69 dialyzer on Prisma Flex (Baxter) CRRT machines during continuous venovenous hemodiafiltration (CVVHDF). The targeted CRRT dose in all the study patients was 25-30 mL/kg/hour. Based on the published literature, we have developed a working protocol (Appendix 1) for managing patients on CRRT using RCA., Results: A total of 159 patients were analyzed for the study. The median [interquartile range (IQR)] filter life using RCA was 30 (12-55) hours. Filter clotting was observed in 33.3% of patients. Citrate accumulation was present in 52.25% of patients, but no CRRT was discontinued as citrate accumulation resolved after following the corrective steps in the protocol. None of the patients had citrate toxicity. Chronic liver disease (CLD) ( p ≤ 0.001) and those who were post-living donor liver transplant recipients ( p = 0.004) had a statistically significant increase in citrate accumulation. Also, patients who had higher lactate at baseline (6 hours post-CRRT initiation), had a higher chance of citrate accumulation., Conclusion: Our RCA protocol provides a safe approach to regional anticoagulation during CRRT in critically ill patients., How to Cite This Article: Pachisia AV, Kumar GP, Harne R, Jagadeesh KN, Patel SJ, Pal D, et al . Protocolized Regional Citrate Anticoagulation during Continuous Renal Replacement Therapy: A Single Center Experience. Indian J Crit Care Med 2024;28(9):859-865., Competing Interests: Source of support: Nil Conflict of interest: Dr Deepak Govil is associated as the Associate Editor of this journal and this manuscript was subjected to this journal's standard review procedures, with this peer review handled independently of this editorial board member and his research group.Conflict of interest: Dr Deepak Govil is associated as the Associate Editor of this journal and this manuscript was subjected to this journal's standard review procedures, with this peer review handled independently of this editorial board member and his research group., (Copyright © 2024; The Author(s).)

Introduction: Pulmonary abscess is a complication of lung infection with localized necrosis and purulent cavity formation. Pulmonary abscesses are typically managed using antibiotic therapy with anatomic surgical resection reserved as a rescue. Percutaneous drainage is considered relatively contraindicated in some centers due to perceived risk of bronchopleural fistula. However, drain placement has been frequently employed at our institution. The purpose of this study was to review and describe our longitudinal experience., Methods: Medical records of children diagnosed with lung abscess and treated with percutaneous drainage from 2005 through 2023 were reviewed. Patient clinical parameters, follow-up imaging, and clinical outcomes were evaluated., Results: Percutaneous drainage (n = 24) or aspiration alone (n = 4) under imaging guidance was performed by interventional radiologists for 28 children with lung abscesses. A single catheter (8-12 Fr) was deployed in the pulmonary abscess cavity and remained for a median of 6 days (IQR: 6-8 days). The median hospital stay was 10 days (IQR: 8.8-14.8 days). The technical success rate for percutaneous drainage or aspiration of primary pulmonary abscesses was 100% (26/26). Two children were later diagnosed with secondarily infected congenital pulmonary airway malformations that were both successfully drained and ultimately surgically resected. The abscess cavities resolved in all patients and catheters were removed upon clinical, radiographic, and laboratory improvement. Complications included the presence of two bronchopleural fistula, both of which were treated with immediate pleural drain placement., Conclusion: Percutaneous drainage of pulmonary abscesses is an effective therapeutic option in children and can be considered alongside antibiotics as part of the initial treatment for pulmonary abscesses. Bronchopleural fistula can occur, but at a lower frequency than previously reported., Level of Evidence: Level V., (Copyright © 2024 Elsevier Inc. All rights reserved.)

How to cite this article: Govil D, Chandrasekaran A, Pachisia AV, Harne R, Patel SJ, Pal D. Author Response: Emphasizing Patient-centered Outcomes and Improved Exclusion Criteria in Randomized Control Trials for Clinical Nutrition in ICU. Indian J Crit Care Med 2024;28(8):806-807., Competing Interests: Source of support: Nil Conflict of interest: NoneConflict of interest: None, (Copyright © 2024; The Author(s).)

Catastrophic spontaneous spinal epidural hematoma (SSEH) following thrombolysis poses a complex intersection of neurosurgical and cardiological challenges. This case report presents the institutional experience of a 66-year-old female who developed rapid-onset compressive myelopathy after thrombolysis for inferior wall myocardial infarction with injection streptokinase. SSEH, although rare, demands prompt recognition due to its potential for permanent neurologic injury and mortality. The discussion highlights the clinical significance, anatomical considerations, and multidisciplinary approach requisite for accurate diagnosis and effective management of SSEH. The conclusion underscores the necessity for clinicians, particularly cardiologists administering thrombolytic therapies, to consider SSEH in postthrombolysis patients presenting with neurological deficits., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Craniovertebral Junction and Spine.)

Objective:  The purpose of this study is to understand experiences of respectful maternity care (RMC) from the perspective of birthing people in the United States from 2013 to 2018., Methods:  We conducted an online cross-sectional survey of United States birthing people ages 18-50 in April 2018 using SurveyMonkey Audience. Quantitative survey data consisted of demographics and responses to RMC indicators. Qualitative data consisted of comments from individuals regarding their birth experiences., Results:  1036 birthing people participated in the survey. Most births (95%) occurred in hospitals. 16.3% of Black or African American participants reported discrimination compared to 5.5% of participants who did not identify as Black or African American (p < 0.001). Participants who speak a language other than English were also more likely to report discrimination. 19.5% of all respondents felt neglected during their birth experience. Most prevalent experiences of disrespect and mistreatment were related to neglect (most commonly in postpartum phase of care), poor interpersonal communication, lack of respect for patient wishes, negative experience with breastfeeding services, peripartum complications, and discrimination., Conclusion for Practice: Birthing people in the United States experience many forms of mistreatment, particularly those who identify as Black or African American or speak a language other than English. Patients described experiencing neglect most commonly after birth-an opportunity to improve the provision of RMC postpartum. Strategies to improve quality of maternal health care in the United States should include the provision of RMC as part of a larger effort to reduce inequities in maternal health experiences and outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim and Background: Sarcopenia is a substantial contributor to intensive care unit (ICU)-acquired weakness and is associated with significant short- and long-term outcomes. It can, however, be mitigated by providing appropriate nutrition. Indirect calorimetry (IC) is believed to be the gold standard in determining caloric targets in the dynamic environment of critical illness. We conducted this study to compare the effect of IC vs weight-based (25 kcal/kg/day) feeding on quadriceps muscle thickness (QMT) by ultrasound in critically ill patients., Materials and Methods: A prospective study was conducted on 60 mechanically ventilated patients randomized to two groups [weight-based equation (WBE) group or the IC group] in medical ICU after obtaining institutional ethics committee approval, and fed accordingly. The right QMT measurement using ultrasound and caloric targets were documented on day 1, 3 and 7 and analyzed statistically. The IC readings were obtained from the metabolic cart E-COVX Module TM ., Results: The baseline demographics, APACHE-II, NUTRIC score, and SOFA scores on day 1, 3, and 7 were comparable between the two groups. The resting energy expenditure (REE) obtained in the IC group was significantly less than the WBE energy targets and the former were fed with significantly less calories. A significantly less percent reduction of QMT in the IC group compared with the WBE group was observed from day 1 to day 3, day 3 to day 7, and day 1 to day 7., Conclusion: From our study, we conclude that IC-REE-based nutrition is associated with lesser reduction in QMT and lesser calories fed in critically ill mechanically ventilated patients compared from WBE. CTRI registration-CTRI/2023/01/049119., How to Cite This Article: Chandrasekaran A, Pal D, Harne R, Patel SJ, Jagadeesh KN, Pachisia AV, et al . Comparison between Effect of Indirect Calorimetry vs Weight-based Equation (25 kcal/kg/day)-guided Nutrition on Quadriceps Muscle Thickness as Assessed by Bedside Ultrasonography in Medical Intensive Care Unit Patients: A Randomized Clinical Trial. Indian J Crit Care Med 2024;28(6):587-594., Competing Interests: Source of support: Nil Conflict of interest: Dr Deepak Govil is associated as Associate Editor of this journal and this manuscript was subjected to this journal's standard review procedures, with this peer review handled independently of the Associate Editor and his research group., (Copyright © 2024; The Author(s).)

AgRP neurons in the arcuate nucleus of the hypothalamus (ARC) coordinate homeostatic changes in appetite associated with fluctuations in food availability and leptin signaling. Identifying the relevant transcriptional regulatory pathways in these neurons has been a priority, yet such attempts have been stymied due to their low abundance and the rich cellular diversity of the ARC. Here we generated AgRP neuron-specific transcriptomic and chromatin accessibility profiles from male mice during three distinct hunger states of satiety, fasting-induced hunger, and leptin-induced hunger suppression. Cis-regulatory analysis of these integrated datasets enabled the identification of 18 putative hunger-promoting and 29 putative hunger-suppressing transcriptional regulators in AgRP neurons, 16 of which were predicted to be transcriptional effectors of leptin. Within our dataset, Interferon regulatory factor 3 (IRF3) emerged as a leading candidate mediator of leptin-induced hunger-suppression. Measures of IRF3 activation in vitro and in vivo reveal an increase in IRF3 nuclear occupancy following leptin administration. Finally, gain- and loss-of-function experiments in vivo confirm the role of IRF3 in mediating the acute satiety-evoking effects of leptin in AgRP neurons. Thus, our findings identify IRF3 as a key mediator of the acute hunger-suppressing effects of leptin in AgRP neurons., (© 2024. The Author(s).)

Coronary artery disease (CAD) is still a serious global health issue that has a substantial impact on death and illness rates. The goal of primary prevention strategies is to lower the risk of developing CAD. Nevertheless, current methods usually rely on simple risk assessment instruments that might overlook significant individual risk factors. This limitation highlights the need for innovative methods that can accurately assess cardiovascular risk and offer personalized preventive care. Recent advances in machine learning and artificial intelligence (AI) have opened up interesting new avenues for optimizing primary preventive efforts for CAD and improving risk prediction models. By leveraging large-scale databases and advanced computational techniques, AI has the potential to fundamentally alter how cardiovascular risk is evaluated and managed. This review looks at current randomized controlled studies and clinical trials that explore the application of AI and machine learning to improve primary preventive measures for CAD. The emphasis is on their ability to recognize and include a range of risk elements in sophisticated risk assessment models., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Patel et al.)

This special article is the third in an annual series of the Journal of Cardiothoracic and Vascular Anesthesia that highlights significant literature from the world of graduate medical education published over the past year. Major themes addressed in this review include the potential uses and pitfalls of artificial intelligence in graduate medical education, trainee well-being and the rise of unionized house staff, the effect of gender and race/ethnicity on residency application and attrition rates, and the adoption of novel technologies in medical simulation and education. The authors thank the editorial board for again allowing us to draw attention to some of the more interesting work published in the field of graduate medical education during 2023. We hope that the readers find these highlights thought-provoking and informative as we all strive to successfully educate the next generation of anesthesiologists., Competing Interests: Declaration of competing interest AKM serves on the Scientific Advisory Board of Attgeno AB, a privately held pharmaceutical company. The other authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We quantified antibiotic prescribing for ambulatory pediatric acute respiratory illness at 22 institutions in "pre-shortage" (Jan 2019-Sep 2022) and "shortage" (Oct 2022-Mar 2023) periods for amoxicillin. While acute respiratory illness prescribing increased across settings, the proportion of amoxicillin prescriptions decreased. Variation was seen within and between institutions., (Copyright © 2024 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Spontaneous rupture of the extensor pollicis longus (EPL) tendon following both nonoperative and operative treatment of distal radius fractures has been well described., Purpose: The purpose of this study was to assess long-term outcomes of extensor indicis proprius to EPL tendon transfers for patients following distal radius fracture and EPL tendon repair., Study Design: Retrospective case series focusing on long-term clinical outcomes., Methods: A retrospective review was conducted for patients who sustained a distal radius fracture and subsequently underwent extensor tendon transfer from 2005-2015 at a private practice center. Outcome measures including index finger (IF) metacarpophalangeal (MCP) and thumb interphalangeal (IP) active range of motion (ROM), digital extension against resistance, subjective complaints, and QuickDASH scores were recorded at final follow-up., Results: Seven patients were included in the study. There were six females and one male subject, mean age of 54 ± 13 years at injury of EPL, and 5/7 involved the left upper extremity. For isolated function, 7/7 (100%) patients had isolated, active IF MCP extension, 6/7 (86%) could extend IF MCP and thumb IP against resistance. Mean IF MCP extension was 1° ± 2°, mean IF MCP flexion was 89° ± 2°, mean thumb IP extension was -5° ± 4°, and mean thumb IP flexion was 67° ± 15°. Mean QuickDASH score was 16 ± 14., Conclusions: This series shows good long-term functional and patient reported outcomes in patients following extensor indicis proprius to EPL tendon transfers at a single center., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Stimulator of interferon genes (STING) is a dimeric transmembrane adapter protein that plays a key role in the human innate immune response to infection and has been therapeutically exploited for its antitumor activity. The activation of STING requires its high-order oligomerization, which could be induced by binding of the endogenous ligand, cGAMP, to the cytosolic ligand-binding domain. Here we report the discovery through functional screens of a class of compounds, named NVS-STGs, that activate human STING. Our cryo-EM structures show that NVS-STG2 induces the high-order oligomerization of human STING by binding to a pocket between the transmembrane domains of the neighboring STING dimers, effectively acting as a molecular glue. Our functional assays showed that NVS-STG2 could elicit potent STING-mediated immune responses in cells and antitumor activities in animal models., (© 2023. The Author(s).)

The interactions of ligand-functionalized nanoparticles with the cell membrane affect cellular uptake, cytotoxicity, and related behaviors, but relating these interactions to ligand properties remains challenging. In this work, we perform coarse-grained molecular dynamics simulations to study how the adsorption of ligand-functionalized cationic gold nanoparticles (NPs) to a single-component lipid bilayer (as a model cell membrane) is influenced by ligand end group lipophilicity. A set of 2 nm diameter NPs, each coated with a monolayer of organic ligands that differ only in their end groups, was simulated to mimic NPs recently studied experimentally. Metadynamics calculations were performed to determine key features of the free energy landscape for adsorption as a function of the distance of the NP from the bilayer and the number of NP-lipid contacts. These simulations revealed that NP adsorption is thermodynamically favorable for all NPs due to the extraction of lipids from the bilayer and into the NP monolayer. To resolve ligand-dependent differences in adsorption behavior, string method calculations were performed to compute minimum free energy pathways for adsorption. These calculations revealed a surprising nonmonotonic dependence of the free energy barrier for adsorption on ligand end group lipophilicity. Large free energy barriers are predicted for the least lipophilic end groups because favorable NP-lipid contacts are initiated only through the unfavorable protrusion of lipid tail groups out of the bilayer. The smallest free energy barriers are predicted for end groups of intermediate lipophilicity which promote NP-lipid contacts by intercalating within the bilayer. Unexpectedly, large free energy barriers are also predicted for the most lipophilic end groups which remain sequestered within the ligand monolayer rather than intercalating within the bilayer. These trends are broadly in agreement with past experimental measurements and reveal how subtle variations in ligand lipophilicity dictate adsorption mechanisms and associated kinetics by influencing the interplay of lipid-ligand interactions.

Background: Exoscope use in spinal neurosurgery has become a promising surgical option providing enhanced operative field visibility and ergonomics. However, data on its use in spine surgery are underreported in the literature. We aimed to assess the intraoperative outcomes in exoscope-assisted spine surgery compared with similar procedures performed using the operative microscope., Methods: A retrospective review was performed of all spinal surgeries performed using an exoscope and, subsequently, an equal number of operative microscope cases performed by 2 senior surgeons at a single institution from 2016 to 2023. The variables included demographics, clinical presentation, surgical treatment, and operative outcomes., Results: A total of 123 exoscope spinal surgeries were performed on 116 unique patients with a mean age of 67 ± 14 years, of whom 60 (52%) were women. The microscope group included 126 surgeries on 120 unique patients with a mean age of 62 ± 14 years, of whom 53 (45%) were women. The mean blood loss (28 mL vs. 132 mL; P = 0.0009), operative time (83 minutes vs. 103 minutes; P = 0.006), and length of stay (1.04 days vs. 1.73 days; P = 0.02) were significantly less for the exoscope group than for the microscope group., Conclusions: The use of the exoscope resulted in a shorter operative time, less blood loss, a shorter length of stay, and favorable clinical outcomes compared with the use of the operative microscope. Neurosurgeons should consider this seemingly efficacious and ergonomically favorable visual technology for spinal surgeries., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Adolescent emergency department (ED) patients have unmet social needs that contribute to ED use. This study aimed to evaluate the effect of social needs navigation for adolescents on subsequent ED visits and community resource use and to identify characteristics associated with elevated social risk., Methods: Between July 2017 and August 2019, we used a random date generator to establish intervention and control group enrollment dates. All adolescents completed a social needs survey. Adolescents enrolled on intervention dates received in-person, risk-tailored social needs navigation. Those enrolled on control dates received a preprinted resource guide. We used chart review and follow-up calls to assess 12-month ED revisits and community resource use. Logistic regression was used to compare these outcomes between groups. We measured the association between ≥3 reported unmet needs and characteristics hypothesized a priori to be associated with elevated social risk (nonurgent visits, obesity, or any of nine "socially sensitive" chief complaints) using logistic regression., Results: A total of 399 adolescents were randomized. There was no difference between groups in the number of ED revisits. There was increased community resource use in the intervention group (adjusted odds ratio [aOR]: 3.5 [95% confidence interval {CI}: 1.5, 8.2]). Adolescents with a socially sensitive chief complaint had increased odds of ≥3 unmet needs (aOR: 2.2 [95% CI: 1.3, 3.6]), as did those with food insecurity in a post hoc analysis (aOR: 9.9 [95% CI: 4.0, 24.6])., Discussion: Social needs navigation increased community resource use but not subsequent ED visits. Adolescents with socially sensitive chief complaints or food insecurity reported increased unmet needs., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background and objectives The quest for an accurate and reliable non-invasive method of assessing cardiac output in critically ill patients is still ongoing. Carotid artery Doppler is a promising non-invasive, reproducible, and feasible bedside monitor. So we compared the change in cardiac output derived from arterial pressure waveforms (pulse contour analysis) with that from carotid artery Doppler-derived measurements, in post-major elective abdominal surgery patients. Materials and methods We conducted a prospective observational study in 30 adult post-major elective abdominal surgery patients admitted to the Gastroenterology and Liver Transplant intensive care unit postoperatively on mechanical ventilator support, who were found to be fluid responsive clinically on passive leg raise (PLR) test. Demographics and vasopressor support were recorded. Hemodynamic parameters including heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), cardiac output (CO) using arterial pulse contour analysis (Vigileo monitor/FloTrac® sensor; Edwards Lifesciences, Irvine, California, United States), and carotid blood flow (CBF) were recorded on the baseline, pre- and post- PLR, and post fluid bolus administration. Balanced salt solution at the rate of 6ml/kg over 20 minutes was given as a fluid bolus. Results Of the 30 patients who were included in the study, 16 patients (53.3%) were on vasopressor support, mean (± SD) age of the patients was 52.93 (± 8.13) years. There was a significant increase in the SBP (mmHg) pre- to post-PLR, that is, 112.2±15.57 and 118.7±14.96, respectively (p-value = 0.001). Also from pre-PLR to post-fluid bolus administration, the increase in SBP was significant, 112.2±15.57 and 121.93±13.96, respectively (p-value = 0.001). The change in cardiac output measured using Vigileo and CBF from pre- to post-PLR (7.66±1.45 to 9.14±1.76, p< 0.001 for Vigileo and 8.10±1.66 to 9.72±1.99, p<0.001 for CBF) and pre-PLR to post fluid administration (7.66±1.45 to 9.39±1.77, p< 0.001 for Vigileo and 8.10±1.66 to 10.31±2.26, p< 0.001 for CBF) were significant. There was a positive correlation between the change in cardiac output as measured from arterial pulse contour analysis technique (Vigileo) and that measured from CBF (r=0.884) pre- and post-PLR. There was a significant correlation between cardiac output measurements derived from two techniques, before PLR, after PLR, and after fluid expansion (p< 0.001 for each variable). The change in cardiac output before PLR and after fluid expansion was also correlated by both the techniques (correlation coefficient being, r=0.781). Conclusion There was a significant positive correlation of the CO (absolute and change) measurements pre- and post-interventions (that is, PLR and fluid bolus administration) as made by pulse contour analysis (Vigileo) and by CBF in post-surgical patients. Pulse wave Doppler of CBF could be used as a surrogate for invasive measures of CO measurement for prediction of fluid responsiveness in this subgroup. Further larger studies can be performed to validate the same., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Karmarkar et al.)

Background: Post-exposure prophylaxis (PEP) with varicella immunoglobulin is recommended to minimize risk of varicella complications for high-risk children. However, providers frequently use alternatives like acyclovir or intravenous immunoglobulin., Methods: A retrospective cohort study was conducted of PEP for varicella in children from January 2009 to December 2019. Data were provided by 47 children's hospitals who participate in the Pediatric Health Information Systems database. Patients with clinical encounters for varicella exposure were reviewed. Choice of varicella PEP regimens, including differences by underlying condition and institution, and incidence of varicella disease were determined., Results: A total of 1704 patients with first clinical encounters for varicella met inclusion criteria. Of these patients, 509 (29.9%) were prescribed PEP after varicella exposure, and 65 (3.8%) ultimately had a subsequent encounter for varicella disease. Of 509 patients who received PEP, acyclovir was most frequently prescribed (n = 195, 38.3%), followed by varicella immunoglobulin (n = 146, 28.7%), IVIG (n = 115, 22.6%), and combination therapy (n = 53, 10.4%). The highest proportion of varicella immunoglobulin use (10/20, 50%) was amongst children with diagnoses of rheumatological/gastrointestinal conditions. The highest proportion of acyclovir use (29/684, 4.2%) was amongst children with diagnoses of oncology/stem cell transplant conditions. The proportion of patients who subsequently had clinical encounters for varicella disease was highest for Acyclovir (30/195, 15.4%) followed by varicella immunoglobulin (5/146, 3.4%), combination therapy (2/53, 3.8%), and intravenous immunoglobulin alone (0/115) (P < .0001)., Conclusions: Varicella PEP in high-risk children was highly varied among children's hospitals. In our dataset, use of acyclovir was associated with a higher rate of subsequent encounters for Varicella disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The aim of this study was to validate the use of temperature sensors to accurately measure thermoplastic volar forearm splint wear in a healthy cohort of volunteers using 5- and 15-minute temperature measurement intervals., Methods: A prospective diagnostic study was performed to evaluate the diagnostic accuracy of temperature sensors in monitoring splint wear in 8 healthy volunteers between December 2022 and June 2023. Temperature sensors were molded into thermoplastic volar forearm splints. Volunteers who were familiar with the study aims were asked to keep an exact log of the time spent wearing the splint ("actual wear time"). Sensors recorded temperatures every 5 or 15 minutes, and separate algorithms were developed to determine the sensor-detected wear time compared with the actual wear time as the gold standard. The algorithms were then externally validated with the total population., Results: The 5-minute and 15-minute algorithms demonstrated excellent sensitivity (99.1% vs 96.6%), specificity (99.9% vs 99.9%), positive (99.4% vs 99.5%) and negative (99.9% vs 99.3%) predictive value, and diagnostic accuracy (99.8% vs 99.3%), respectively. The 5-minute algorithm recorded 99.5% of the total splint hours, whereas the 15-minute algorithm recorded 96.1%. There was no significant difference between the actual time per wear session (5.4 ± 2.7 hours) and the time estimated by the 5-minute algorithm (5.4 ± 2.6 hours; P = .40), but there was a significant difference for the 15-minute algorithm (5.2 ± 2.6 hours; P < .001)., Conclusion: Temperature sensors can be used to accurately monitor thermoplastic volar forearm splint wear., Level of Evidence: Diagnostic II., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: All authors declared research grant funding from the Hand Rehabilitation Foundation. M.N.G. declared additional grant funding for research support from Orthofix and consulting fees from Arthrex and Tigon. A.L.O. declared additional research support from Auxilium and Skeletal Dynamics; royalties from Elsevier and Skeletal Dynamics; consulting fees from AM Surgical, Arthrex, and Auxilium; paid speaking for Accumed, Arthrex, and Auxilium; and is on the editorial board of Orthopedics Today and Wrist.

Background and Objectives: Patient and Family Centered I-PASS (PFC I-PASS) emphasizes family and nurse engagement, health literacy, and structured communication on family-centered rounds organized around the I-PASS framework (Illness severity-Patient summary-Action items-Situational awareness-Synthesis by receiver). We assessed adherence, safety, and experience after implementing PFC I-PASS using a novel "Mentor-Trio" implementation approach with multidisciplinary parent-nurse-physician teams coaching sites., Methods: Hybrid Type II effectiveness-implementation study from 2/29/19-3/13/22 with ≥3 months of baseline and 12 months of postimplementation data collection/site across 21 US community and tertiary pediatric teaching hospitals. We conducted rounds observations and surveyed nurses, physicians, and Arabic/Chinese/English/Spanish-speaking patients/parents., Results: We conducted 4557 rounds observations and received 2285 patient/family, 1240 resident, 819 nurse, and 378 attending surveys. Adherence to all I-PASS components, bedside rounding, written rounds summaries, family and nurse engagement, and plain language improved post-implementation (13.0%-60.8% absolute increase by item), all P < .05. Except for written summary, improvements sustained 12 months post-implementation. Resident-reported harms/1000-resident-days were unchanged overall but decreased in larger hospitals (116.9 to 86.3 to 72.3 pre versus early- versus late-implementation, P = .006), hospitals with greater nurse engagement on rounds (110.6 to 73.3 to 65.3, P < .001), and greater adherence to I-PASS structure (95.3 to 73.6 to 72.3, P < .05). Twelve of 12 measures of staff safety climate improved (eg, "excellent"/"very good" safety grade improved from 80.4% to 86.3% to 88.0%), all P < .05. Patient/family experience and teaching were unchanged., Conclusions: Hospitals successfully used Mentor-Trios to implement PFC I-PASS. Family/nurse engagement, safety climate, and harms improved in larger hospitals and hospitals with better nurse engagement and intervention adherence. Patient/family experience and teaching were not affected., (Copyright © 2024 by the American Academy of Pediatrics.)

Effective eradication of leukemic stem cells (LSCs) remains the greatest challenge in treating acute myeloid leukemia (AML). The immune receptor LAIR-1 has been shown to regulate LSC survival; however, the therapeutic potential of this pathway remains unexplored. We developed a therapeutic LAIR-1 agonist antibody, NC525, that induced cell death of LSCs, but not healthy hematopoietic stem cells in vitro, and killed LSCs and AML blasts in both cell- and patient-derived xenograft models. We showed that LAIR-1 agonism drives a unique apoptotic signaling program in leukemic cells that was enhanced in the presence of collagen. NC525 also significantly improved the activity of azacitidine and venetoclax to establish LAIR-1 targeting as a therapeutic strategy for AML that may synergize with standard-of-care therapies.

Competing Interests: Declaration of Competing Interest Christian Bermudez is a member of the medical advisory board for Abiomed and Abbott; Marisa Cevasco consults for Abiomed; Joyce Wald is on the speakers’ bureau for Impulse Dynamics and advisory board for Abiomed and Boston Scientific.

The field of lung transplantation (LTx) has expanded rapidly since its inception in the early 1960s with the work of James Hardy and colleagues at the University of Mississippi from the work of local single specialty physicians into an international multidisciplinary specialty. Advancements throughout the next several decades have led to the completion of over 70,000 lung transplants worldwide. The unique challenges presented by patients with end-stage lung disease have both evolved and remained consistent since then, yet these challenges are being answered with major improvements and advancements in perioperative care in the 21st century. The current practice of LTx medicine is fundamentally multidisciplinary, and members of the LTx team includes surgeons, physicians, and allied health staff. The integration of anesthesiologists into the LTx team as well as the multidisciplinary nature of LTx necessitates anesthetic considerations to be closely incorporated into emerging surgical, medical, and systems techniques for patient care. This review discusses a host of emerging strategies across the spectrum of LTx, including efforts to expand the donor pool, utilization of perioperative extracorporeal life support, perioperative echocardiography, and anesthetic techniques to mitigate primary graft dysfunction that have all contributed to improved long term outcomes in LTx patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-4602/coif). The series “Highlights in Anesthesia and Critical Care Medicine” was commissioned by the editorial office without any funding or sponsorship. AKM is on the Scientific Advisory Board for Attgeno AB, and all compensation goes to Mayo Clinic. The authors have no other conflicts of interest to declare., (2023 Annals of Translational Medicine. All rights reserved.)

Background: As nurse practitioners and physician assistants (APPs) become more prevalent in delivering pediatric care, their involvement in antimicrobial stewardship efforts increases in importance. This project aimed to create and assess the efficacy of a problem-based learning (PBL) approach to teaching APPs antimicrobial stewardship principles., Methods: A PBL education initiative was developed after communication with local APP leadership and focus group feedback. It was offered to all APPs associated with Lurie Children's Hospital of Chicago. Participants completed a survey which assessed opinions on antimicrobial stewardship and included knowledge-based questions focused on antimicrobial stewardship. Prescriptions for skin and soft tissue infections associated with APPs were recorded via chart review before and after the education campaign., Results: Eighty APPs participated in the initial survey and teaching initiative with 44 filling out the 2-week follow-up and 29 filling out the 6-month follow-up. Subjective opinions of antimicrobial stewardship and comfort with basic principles of AS increased from pre-intervention. Correct responses to knowledge-based assessments increased from baseline after 2-week follow-up (p < 0.01) and were maintained at the 6-month follow-up (p = 0.03). Simple skin and soft tissue infection prescriptions for clindamycin went from 44.4% pre-intervention to 26.5% (p = 0.2) post-intervention., Conclusions: A PBL approach for APP education on antimicrobial stewardship can be effective in increasing knowledge and comfort with principles of antimicrobial stewardship. These changes are maintained in long-term follow-up. Changes in prescribing habits showed a strong trend towards recommended empiric therapy choice. Institutions should develop similar education campaigns for APPs., Competing Interests: The authors have indicated they have no conflicts of interest relevant to this article to disclose., (© The Author(s) 2023.)

Ventral hernias with large defects (≥ 2 cm) are managed with tension free mesh repair. The growing consensus that sublay (retrorectus) mesh repair is superior to onlay mesh repair due to fewer complications is based on literature dominated by retrospective studies from high and upper-middle income countries. There is thus a need of more prospective studies from various countries to resolve the controversy. The objective of this study was to compare the outcomes of onlay versus sublay mesh repair in the management of ventral hernias. Our single centre, prospective comparative study set in a low-middle income country comprised of 60 patients with a ventral hernia undergoing open surgical repair using either onlay technique (n = 30) or sublay technique (n = 30). Surgical site infections, seroma formation, recurrence were found in 3.33%, 6.67%, 0% patients in sublay repair group and in 16.67%, 20%, 6.67% patients in onlay repair group respectively. Mean duration of surgery, mean Visual Analogue Scale (VAS) score for chronic pain, mean duration of hospital stay were 46 min, 4.5, 8 days in onlay repair group and 61 min, 4.2, 6 days in sublay repair group respectively. Onlay repair group was associated with shorter duration of surgery. However, sublay repair was associated with lesser rates of surgical site infections, chronic pain and recurrence than onlay repair. Sublay mesh repair had better outcomes than onlay mesh repair for the management of ventral hernias, however superiority of any one technique could not be established., (© 2023. Italian Society of Surgery (SIC).)

Background: Therapies to prevent alcohol-associated liver disease (ALD) in high-risk patients are needed., Aims: In this retrospective association study, we examined whether patients with alcohol use disorder (AUD) who reported greater exercise were less likely to develop liver disease., Methods: In this retrospective cohort study, we used the Mass General Brigham Biobank to investigate the impact of both moderate-high and light-intensity exercise on the development of ALD in patients with AUD, using clinician-provided diagnostic International Classification of Diseases 10 codes. Exercise was evaluated using a questionnaire completed after an AUD diagnosis, and before evidence of liver disease. Cox regressions were used to generate hazard ratios (HRs) for the development of ALD., Results: 1987 patients met inclusion criteria. These patients were followed for an average of 10.7 years. In multivariable analyses, we found that patients that reported at least 2.5 h of moderate-high intensity exercise/week (confidence interval recommendation for exercise) were less likely to develop ALD compared to patients that did not exercise (HR: 0.26, 95%CI: 0.085-0.64, P = 0.007). Indeed, each hour of moderate-high intensity exercise was associated with progressively decreasing odds of developing ALD (HR: 0.76, 95%CI: 0.58-0.91, P = 0.02). Conversely, patients who did not engage in any moderate-high intensity exercise were more likely to develop ALD (HR: 2.76, 95%CI: 1.44-5.40, P = 0.003)., Conclusions: In our cohort, patients with AUD who reported moderate-high intensity exercise showed a lower association with incidence of ALD development than patients who did not exercise., (© The Author(s) 2023. Medical Council on Alcohol and Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)