Faculty Bibliography

BACKGROUND:Acute GI bleeding (AGIB) can be associated with significant mortality. Topical endoscopic hemostatic powders (TEHPs) have become established as one of the endoscopic treatment modalities for AGIBs. There is no dedicated consensus on the role of TEHPs in the GIB algorithm. OBJECTIVE:We aimed to develop expert-led consensus statements to provide guidance on the use of TEHPs in AGIBs. DESIGN/METHODS:A team of 15 experts in the field of acute AGIB from 8 countries was recruited to construct consensus statements on the use of TEHPs. A first meeting was held to define statements. Using the RAND/UCLA appropriateness method, they voted on statements by combining expert collective judgment and best available evidence in a 2-round voting process. Statements were rated on a 9-point interval scale (1 to 9). Four statistical methods were used to delineate statements that satisfied all criteria of appropriateness. For a statement to be considered appropriate, it had to meet all statistical definitions of appropriateness showing consensus agreement. RESULTS:Following round 2, 11 final statements were scored as appropriate, reaching overall consensus. Key recommendations include that TEHPs are effective in achieving hemostasis in malignancy-related GIBs, can be used as "salvage" therapy for nonvariceal GIBs and can be used as a bridge to definitive nonendoscopic therapy. CONCLUSION/CONCLUSIONS:We present a dedicated international consensus statement aimed at providing guidance to clinicians on best practice use of TEHPs in patients with AGIBs. There was consensus among the panel on the need for future trials to compare the use of different hemostatic powders in patients presenting with GIB.

BACKGROUND/UNASSIGNED:Alterations in microtubule dynamics have been shown to affect cardiomyocyte membrane stiffness and modulate ion channels, including the cardiac sodium channel. While conditions, such as heart failure and Duchenne muscular dystrophy, are associated with increased detyrosination of microtubules and reduced sodium current, a potential role for microtubule detyrosination in arrhythmogenic cardiomyopathy has not been explored. We here investigated the impact of microtubule detyrosination on membrane stiffness, cardiac sodium channel distribution, and function in mouse and human models of arrhythmogenic cardiomyopathy. METHODS/UNASSIGNED:-c.2013delC, and isogenic control human-induced pluripotent stem cell-derived-cardiomyocytes were incubated for 2 to 4 hours with compounds known to decrease microtubule detyrosination (parthenolide, 10 µmol/L; EpoY, 20 µmol/L) or vehicle (dimethyl sulfoxide). Immunocytochemistry, mechano-scanning ion conductance microscopy, patch-clamp analysis, and stochastic optical reconstruction microscopy were performed. RESULTS/UNASSIGNED:-c.2013delC human-induced pluripotent stem cell-derived-cardiomyocytes displayed increased microtubule detyrosination and reduced sodium current compared with isogenic control human-induced pluripotent stem cell-derived-cardiomyocytes, which were both prevented by parthenolide and EpoY. CONCLUSIONS/UNASSIGNED:Increased microtubule detyrosination secondary to loss of PKP2 impacts cardiomyocyte (dys)function beyond the desmosome, contributing to both electrical and mechanical alterations in the setting of arrhythmogenic cardiomyopathy. Our findings identify microtubule detyrosination as a novel therapeutic target in pathophysiological conditions, such as arrhythmogenic cardiomyopathy, aimed at improving both contractile and electrical function.

BACKGROUND:This study evaluated differences in surgical and clinical outcomes among patients who have identical versus different implant sizes in sequential total knee arthroplasty (TKA) surgeries. METHODS:We retrospectively reviewed patients who underwent primary, elective, staged, bilateral, same-surgeon, same-prosthesis TKA between 2011 and 2024 at a large academic health system. Patients were grouped by femoral and tibial implant size consistency: same femoral and tibial (SS), different femoral, same tibial, different tibial, same femoral, and different femoral and tibial (DD). RESULTS:A total of 4,536 TKAs were performed in 2,268 patients. The SS had the shortest length of stay compared to DD (51.8 versus 58.2 hours, P < 0.001). The majority had the same femoral (75.6%) and tibial (76.6%) sizes in both knees, whereas polyethylene thickness varied. Undergoing contralateral surgery within one year was associated with receiving the same implant sizes (P < 0.001). The DD were more common in manual surgery, and the SS were more common using navigation assistance (P < 0.001). Different assistance modalities between surgeries increased different femoral, same tibial and DD, whereas the same navigation assistance increased SS (P < 0.001). Complication and revision rates were not significantly different between the groups. All groups showed improvement in their Knee injury and Osteoarthritis Outcome Score for Joint Replacement and Patient-Reported Outcomes Measurement Information System Pain Intensity and Interference scores with no significant intergroup differences (P > 0.05). CONCLUSIONS:Over one-third of patients (37.3%) undergoing staged, bilateral TKA received different implant sizes for at least one component, and over half had different polyethylene thicknesses. Although implant size consistency was influenced by factors such as time between surgeries and assistance modality, these variations did not significantly affect length of stay, complications, or patient-reported outcomes. Surgeons should be aware that minor implant size differences between knees are common, even when using the same prosthesis.

The September 11, 2001, terrorist attacks on the World Trade Center (9/11) exposed both disaster responders and community members to a complex mixture of environmental contaminants, resulting in long-term health consequences. While clinical and research efforts have characterized health effects among adult survivors (community members) and responders, less is known about individuals who were exposed in utero, during childhood, adolescence, or young adulthood. Recognizing this gap, Congress amended the Public Health Service Act (42 U.S.C. § 300mm-51(c)) to establish a Research Cohort for Emerging Health Impacts on Youth to promote research on those individuals who were 21 years of age or younger at the time of exposure. This Commentary reviews the historical development of post-9/11 monitoring, treatment, and research programs, and discusses the unique challenges of conducting research in such a youth cohort 25 years after the event. A central coordinating center supported by community-based field sites offers a promising approach to promoting research among this cohort and addressing critical gaps in understanding the lifelong impacts of 9/11 exposures.

Astrocytes, long considered supportive cells of the central nervous system (CNS), have critical roles in innate immunity. This Review explores immune signaling pathways in astrocytes, including pattern recognition through Toll-like receptors, nucleic acid sensors and inflammasomes. These pathways enable the detection of danger signals and initiate protective responses and endogenous innate immune functions. Downstream signaling pathways, including the interferon, NF-κB and STAT3 pathways, mediate astrocyte reactivity and drive cytokine secretion, antiviral responses, phagocytosis and many other immune functions. While these responses are crucial for CNS health, their dysregulation can contribute to chronic inflammation and neurodegeneration in conditions such as Alzheimer's disease, Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis. Additionally, astrocytes exhibit regional heterogeneity in their immune behaviors, which may influence disease trajectories. We highlight unresolved questions regarding the immune functions of astrocytes, their interplay with professional immune cells and their dual protective and pathological roles.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are common conditions among patients with cirrhosis whose development is associated with increased morbidity and mortality. Recurrent episodes of AKI within this population can ultimately lead to CKD, while patients with underlying CKD are in turn more likely to experience AKI. Determining the etiology of kidney dysfunction in the setting of cirrhosis is often challenging given the considerable limitations of currently available diagnostic tools. Ongoing research into the role of novel serum and urine biomarkers may allow for more timely diagnosis and treatment of kidney injury among patients with cirrhosis. This review provides an overview of kidney dysfunction in cirrhosis with a focus on the role of these emerging biomarkers for diagnosis of AKI and CKD.

BACKGROUND:Telemedicine is a critical military medicine capability in austere, remote, and denied environments where prolonged casualty care and knowledge gaps exist. Despite significant military investment in telemedicine, the literature lacks detailed lessons from real-world cases. METHODS:U.S. Air Force Pararescue missions between 1 January 2010 and 31 December 2020 that included telemedicine consultation were reviewed. Participating flight surgeons (FS) and Pararescuemen (PJ) were interviewed, and available after-action reports were analyzed. Mission parameters, outcomes, and technical or human factors affecting communication were evaluated. RESULTS:Across 13 telemedicine consultations, the 28 patients experienced: cave entrapment (13), trauma (7), burns (4), and illness (4). Consultations were from PJ to FS (11), U.S. Coast Guard to FS (1), and FS to neurosurgery (1). Secondary consultations (7) were from FS to dental (1), dermatology, burn/critical care, orthopedics (2), pediatric anesthesiology, and thoracic surgery specialists. Missions used voice over mobile or satellite phone, text, and email. Recommendations commonly involved medication selection (6), advisement against mission launch (3), and burn care (2). Consultation effectiveness was impacted by unclear directions (3) and degraded communications (2). CONCLUSION/CONCLUSIONS:Telemedicine is valuable to PJs during complicated cases and rarely performed procedures, but cannot replace pre-deployment medical exposure and training. Rehearsals may optimize telemedicine, and training should focus on synchronizing a shared mental model of the patient using well-understood patient report and evaluation tools (ATMIST and MARCH PAWS). Telemedicine may reduce human error, give medics the confidence to take action, and limit the psychological impact of difficult care decisions.

BACKGROUND/UNASSIGNED:Racial and ethnic disparities are a concern in lung cancer screening. OBJECTIVE/UNASSIGNED:To investigate the performance of risk prediction models to define screening eligibility across 4 U.S. racial and ethnic groups. DESIGN/UNASSIGNED:Cohort study. SETTING/UNASSIGNED:United States, Lung Cancer Cohort Consortium. PARTICIPANTS/UNASSIGNED:641 830 participants aged 50 to 80 years with a smoking history from 12 U.S. cohorts, including 6390 Asian, 9781 Hispanic, 39 872 non-Hispanic Black, and 585 787 non-Hispanic White participants. MEASUREMENTS/UNASSIGNED:Calibration and discrimination were quantified for 16 lung cancer prediction models. Then, screening-related metrics were calculated after applying model thresholds to select the same number of eligible participants as the 2021 criteria from the U.S. Preventive Services Task Force (USPSTF-2021). These included eligibility, sensitivity, and efficiency measured as estimated number needed to screen (NNS; the ratio between participants and lung cancer cases) for each strategy or prediction model in each racial and ethnic group. RESULTS/UNASSIGNED:General patterns across the 16 models included substantial underestimation of lung cancer risk in non-Hispanic Black participants (expected-observed ratio < 0.75 for 11 of 16 models), lower discrimination in Asian participants than all other groups (13 of 16 models), and lower discrimination in non-Hispanic Black than non-Hispanic White participants (15 of 16 models). When a same-sized screening-eligible population as USPSTF-2021 (38.0%) was enforced, all risk-based strategies achieved better average estimated screening efficiency and reduced racial and ethnic differences in efficiency compared with USPSTF-2021. The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Model 2012 (PLCOm2012) and Life Years gained From Screening-Computed Tomography model (LYFS-CT) performed best (mean estimated NNS, 36.5 [SD, 8.8] and 40.1 [SD, 8.2], respectively). However, no strategy could simultaneously optimize eligibility, sensitivity, and efficiency while also reducing racial and ethnic differences. LIMITATION/UNASSIGNED:Smaller sample for Asian and Hispanic participants. CONCLUSION/UNASSIGNED:To optimize efficiency and minimize its variation across racial and ethnic groups, risk-based strategies were superior to USPSTF criteria. Further optimization of prediction models for the diverse U.S. population is needed. PRIMARY FUNDING SOURCE/UNASSIGNED:U.S. National Cancer Institute, Lung Cancer Research Foundation, and Cancer Research UK.

Mobile eye-tracking has revolutionized the study of human behavior and cognition by enabling researchers to record eye movements in the real world. However, the dynamic and multimodal nature of mobile eye-tracking data also introduces significant analytical challenges, including the alignment, integration, and interpretation of complex data. To fill these gaps, we present PyNeon, a versatile, community-oriented Python package designed to streamline the analysis of mobile eye-tracking, motion, and video data from the Neon eye-tracking system (Pupil Labs GmbH). We describe how PyNeon provides accessible APIs for reading, preprocessing, epoching, and exporting Neon data. Furthermore, it supports advanced video processing such as mapping between eye movement data and real-world coordinates and dynamic scanpath estimation. PyNeon presents an open-source and extendable framework for analyzing mobile eye-tracking data and forms the foundation for higher-level applications.