Citations

Purpose: Melatonin can protect against oxidative damage and ischemia-induced cell death. 17β-Estradiol (E2) has neuroprotective effects, and its receptors are expressed in the retina. The protective effects of melatonin and E2 against hypoxic stress induced by cobalt chloride (CoCl 2 ) were investigated using human retinal cell lines. Materials and Methods: Human retinal pigment epithelial cells (ARPE-19) and Müller glial cells (MIO-M1) were pretreated for 6 h with either melatonin (200, 400, and 800 µM) or E2 (20, 40, and 80 µM) and then stressed for 48 h with CoCl 2 . Cultures were analyzed for cell metabolism (MTT assay), reactive oxygen species (ROS/H2DCFDA assay), and mitochondrial membrane potential (MMP/JC-1 assay). Results: Melatonin pretreatment significantly increased (i) the cell metabolism in ARPE-19 cells (400 µM, P = 0.0352; 800 µM, P = 0.0016) and MIO-M1 cells (200 µM, P = 0.0341; 400 µM, P = 0.0009) and (ii) mitochondrial membrane potential in ARPE-19 (400 µM, P = 0.0131; 800 µM, P = 0.0096) and also the MIO-M1 cells (800 µM, P = 0.0082) after CoCl 2 hypoxic stress. Pretreatment with E2 improved cell metabolism in ARPE-19 cells (20 µM, P = 0.0076). MIO-M1 cells showed improved metabolism at all E2 concentrations studied and higher mitochondrial membrane potential with E2 40 µM pretreatment ( P = 0.0152). ROS levels were not improved with melatonin or E2 pretreatments. Conclusions: In response to CoCl 2 -induced hypoxic stress, pretreatment with melatonin and E2 can significantly improve the cellular metabolism and mitochondrial membrane potential in human RPE and Müller glial cell lines. Translational Relevance: Our study investigates the protective effects of melatonin and 17β-estradiol against ischemic stress in vitro with the overall goal to improve cellular homeostasis and decrease retinal degeneration.

Abstract Artificial intelligence (AI) encompasses the development of systems that can perform human‐like tasks, such as treatment guidance, decision‐making, pattern recognition and understanding language. Within AI, machine learning and deep learning play pivotal roles in diagnosis and outcome prediction, while natural language processing aids in synthesising large datasets from the electronic medical record. In orthopaedics, AI has demonstrated success in various areas, including image evaluation, surgical planning, outcome prediction, cohort identification and administrative tasks. The purpose of this manuscript was to provide an overview of the benefits of AI implementation within the field of orthopaedics. An additional goal was to address the challenges associated with producing high quality AI‐based research in a rapidly developing field. Level of Evidence Level IV.

Abstract Aims Heart failure with preserved ejection fraction (HFpEF) is one of the most common forms of heart failure with no effective treatment. While chronic systemic inflammation, triggered by comorbidities, is a critical factor of HFpEF pathophysiology and a relevant target for therapy, mechanisms underlying inflammation remain poorly understood. Here, we aim to understand the upstream mechanisms driving inflammation, including immune dysregulation and cellular senescence. Methods and results ZSF1-Obese rats, a cardiometabolic model of HFpEF, were used to investigate systemic and cardiac inflammation, and to characterise the senescent program in immune, circulating endothelial and cardiac cells, before disease onset and onward. Using patient samples, we further evaluated the association between cellular senescence and diagnostic and prognostic markers of HFpEF. Finally, we administered a senolytic - Navitoclax - at two time-points, before and after the appearance of HFpEF. Conclusion ZSF1-Obese rats had increased immune and endothelial senescent cells in their peripheral blood and myocardium, together with exacerbated systemic inflammation and endothelial damage, compared to control ZSF1-Lean rats. Moreover, increased circulating senescent leucocytes were associated with markers of disease severity in patients with HFpEF. Senescent cell clearance decreased circulating B-type natriuretic peptide levels and attenuated inflammation, vascular remodelling, and cardiac fibrosis. Additionally, it improved renal function and reduced pulmonary oedema. Our findings suggest that senotherapeutics may improve the treatment for HFpEF by attenuating systemic effects of the disease whilst reducing cardiac fibrosis and endothelial rarefaction.

Background To evaluate the short-term clinical performance of Symvess (acellular tissue engineered vessel-tyod), formerly known as human acellular vessel, or HAV, compared with autologous vein for the treatment of extremity arterial injury. Methods Subjects treated with acellular tissue engineered vessel (ATEV) from two clinical trials were propensity score-matched on a 1:2 basis to PROspective Observational Vascular Injury Trial (PROOVIT) registry subjects with the same injured artery and treated with autologous vein. Matching characteristics included age, sex, trauma type (penetrating vs blunt), injury severity score, mangled extremity severity score, concomitant fracture, shunt use, and ischemia duration>6 hours. Incidence of outcomes (primary/secondary patency, amputation, conduit infection, reintervention for thrombosis/stenosis, pseudoaneurysm, and death) was assessed by a generalized linear model. Outcomes were assessed at Day 30 (ATEV group) or during initial hospitalization (autologous group). Results ATEV subjects lacking suitable autologous vein (n=67) and PROOVIT subjects treated with autologous vein (n=134) suffered injuries to axillary, brachial, femoral, popliteal, and posterior tibial arteries. Subgroups were clinically similar; Injury Severity Score, Mangled Extremity Severity Score, and duration of follow-up (16 vs 30 days) were higher for the ATEV subgroup. Primary patency for the ATEV versus autologous group was 86.6% versus 91.8%, secondary patency: 91.0% versus 97.7%; amputation: 7.5% versus 8.2%; conduit infection: 1.5% versus 0%; reintervention for thrombosis or stenosis: 6.0% versus 8.2%; and death 4.5% versus 4.5%, respectively. No cases of pseudoaneurysm, true aneurysm, or significant differences between the ATEV and autologous groups for any outcome were observed. Conclusions Short-term outcomes were similar between ATEV subjects without feasible autologous vein, and propensity score-matched autologous vein recipients from the PROOVIT registry. The ATEV may provide effective and safe revascularization in subjects with extremity arterial injury without feasible autologous vein. Level of evidence Level 3, Therapeutic/Care Management

ABSTRACT The American Society for Apheresis (ASFA) Attending Physician Subcommittee of the Physicians' Committee performed an annual review of articles published in 2024 related to apheresis medicine. The 10 seminal apheresis articles selected by the subcommittee members are summarized in this review. PubMed was used to identify manuscripts published in 2024 in four areas of interest: donor apheresis, therapeutic apheresis, apheresis education, and apheresis for cellular therapy. Only full length, peer‐reviewed manuscripts in English with data from human subjects were included. Case reports, review articles, and meta‐analyses were excluded. Articles were considered seminal if they met at least one of the following previously established criteria: novel finding(s), practice‐altering outcomes, international in scope, randomized‐controlled trial, relevant to current clinical practice, and/or provide evidence for category III or IV indications based on the ASFA 9th special issue of the Guidelines on the Use of Therapeutic Apheresis in Clinical Practice‐Evidence‐Based Approach.

Background: The incidence of lymphedema may be as high as 65% among breast cancer patients, varying according to the diagnostic method and locoregional treatment. Therefore, investigations of preventive methods are highly welcomed. Our goal was to conduct a systematic review of the literature about the use of axillary reverse mapping to prevent lymphedema during breast cancer treatment. We hypothesized that identification of arm-draining lymph nodes may decrease the incidence of lymphedema. Methods: On October 7, 2019, we conducted a systematic review of studies in PubMed, Cochrane Clinical Answers, and Cochrane Central Register of Controlled Trials, without time frame or language limitations, on the use of axillary reverse mapping to prevent lymphedema during breast cancer treatment. We excluded articles that investigated other uses of lymphoscintigraphy, such as lymphedema diagnosis or treatment evaluation. Results: Of 104 potential articles found in the literature, 5 studies fulfilled the eligibility criteria. A total of 501 patients were included. Reverse mapping was done with radiography or single-photon emission computed tomography/computed tomography. Moreover, the examination was applied with different treatments, such as axillary lymph node dissection or radiotherapy, allowing preservation of noncompromised lymph nodes. Axillary reverse mapping also had prognostic value and was used with sentinel lymph node biopsy to identify patients at higher risk for lymphedema. Only one study compared the incidence of lymphedema between patients who received standard care or reverse mapping, showing significant benefits of its use. Conclusions: Use of axillary reverse mapping to prevent lymphedema is feasible and seems to provide valuable information for breast cancer treatment. Future studies that compare reverse mapping and standard care are still necessary.

Background: Progressive heart failure cardiogenic shock (HFCS) often requires escalation to temporary or durable mechanical circulatory support (MCS) as a bridge to transplant (BTT). Following the 2018 UNOS allocation changes, our center revised its BTT strategy to optimize support and shorten wait times. At our institution, the Impella 5.5 with SmartAssist via the axillary approach was selectively used for patients who remained refractory to guideline-directed medical therapy, failed single-inotrope therapy, and were not considered suitable durable LVAD candidates by our multidisciplinary heart team. We compared transplant-related outcomes of BTT patients supported with Impella 5.5 versus durable LVAD. Methods: We performed a single-center retrospective review of all heart and heart/kidney transplant candidates at Mayo Clinic Florida from October 2018 to February 2021. INTERMACS profile, baseline characteristics, and perioperative data were collected at the time of device implantation and throughout the transplant hospitalization. Results: A total of 87 heart and 4 heart–kidney transplants were completed. Forty-five patients (49%) required MCS as BTT: 27 (60%) with a durable LVAD and 18 (40%) with an Impella 5.5. All eighteen patients with Impella 5.5 as BTT (100%) were transplanted compared to nineteen patients with durable LVAD (70%), p = 0.001. The median time from listing to transplant was substantially shorter with Impella (32 vs. 696 days, p < 0.001), and this difference persisted across INTERMACS profiles. UNOS status at transplant was more urgent for Impella than LVAD (p < 0.001). Transplant surgery following Impella support required shorter cardiopulmonary bypass time (181 vs. 219 min, p < 0.001) and resulted in lower postoperative vasoactive-inotropic requirements (7.9 vs. 13, p = 0.003). No patients in the Impella group died or were delisted while awaiting transplant, whereas 5 LVAD patients (26%) died or were removed due to LVAD complications (p < 0.001). Conclusions: Our data demonstrates that the use of the Impella 5.5 as BTT was associated with significantly shorter waitlist time, higher transplantation rates, reduced perioperative morbidity, and lower postoperative vasoactive support compared with durable LVAD as BTT. These benefits were achieved despite a higher severity of illness at transplantation in the Impella cohort.

Background: Patients with non-English Language Preference are at risk of adverse health outcomes, particularly at end of life and during serious illness. Medical interpreters often feel unprepared to interpret conversations about serious illness. Best practice guidelines recommend a pre-encounter huddle between clinician and interpreter to better prepare both providers. The CHECK-IN (Check in for Exchange of Clinical and Key Information) guide is a simple communication tool designed to facilitate this pre-encounter huddle. We describe the results of a pilot feasibility study of the CHECK-IN guide performed in a simulation environment. The primary objectives of the study were to evaluate the feasibility, acceptability, and preliminary performance of the CHECK-IN guide. Methods: This U.S.-based study is a single-center simulation-based nonblinded randomized pilot feasibility study. Participating clinicians were randomized to usual practice (control) vs. introduction to the CHECK-IN guide (intervention). Clinicians completed pre- and post-session surveys. Participating clinicians were evaluated using the Faculty Observation Rating Scale (FORS), Interpreter Scale (IS), and Interpreter Impact Rating Scale (IIRS). Results: Participants had a highly favorable opinion on the acceptability, appropriateness, and feasibility of the CHECK-IN tool; 91% of participants agreed/strongly agreed on the acceptability of the tool, 91% agreed/strongly agreed on the appropriateness of the tool, and 100% agreed/strongly agreed on the feasibility of the tool. There were no statistical differences between control and intervention groups for the IS, IIRS, and FORS scores. Conclusion: The CHECK-IN guide is a promising tool to guide a pre-encounter huddle between clinician and interpreter, thereby improving interpreter-mediated communication when having conversations about serious illness.

Importance Adverse events in otolaryngology–head and neck surgery (OHNS) are inconsistently reported. The Clavien-Dindo Classification has been modified and validated in several surgical subspecialties but has yet to be validated in OHNS. Objective To create and validate a modified Clavien-Dindo Classification for OHNS that reflects the severity and duration of harm for complications experienced by patients undergoing OHNS. Design, Setting, and Participants This is a multicenter survey study of subject matter experts (SMEs) from OHNS subspecialties from academic institutions within the US. A literature review identified publications reporting surgical complications in OHNS in the English language between January 2019 and April 2020. Complications were summarized and used to inform a modified Clavien-Dindo Classification. Feedback from internal SMEs was incorporated. Thirty-five clinical vignettes were created, and an electronic survey was sent to SMEs at outside institutions. Each SME was randomly assigned to 1 of 4 groups to evaluate 8 to 9 vignettes. The survey was conducted in September 2023, and data were analyzed from February to May 2024. Exposure Participation in the electronic survey. Main Outcomes and Measures Vignette scores were assessed and the Comprehensive Complication Index (CCI) calculator was used to assess cumulative morbidity. The scale is based on the grading by the Clavien-Dindo Classification and reflects overall morbidity on a scale from 0 (no complication) to 100 (death). Variability of the CCIs between reviewers, the primary outcome, was summarized with the SD. The percentage of reviewers with a high (≥26.2) or low (&amp;lt;26.2) CCI within a vignette was reported. Reliability was summarized using Krippendorff α. Results Of 106 SMEs, 43 (response rate, 40.6%) completed at least 1 vignette. Eighteen of 35 vignettes (51.4%; 95% CI, 34.9%-68.0%) had unanimous high CCI, and 8 of 35 vignettes (22.9%; 95% CI, 8.9%-36.8%) had unanimous low CCI (overall categorical agreement, 74.3%; 95% CI, 59.8%-88.8%). On average, the Krippendorff α was 0.74, indicating moderate reliability. A total of 21 850 OHNS complications were reviewed and categorized as surgical or medical with 12 including subcategorization for specificity. Each category was then assigned a modified OHNS Clavien Dindo classification grade. Conclusions and Relevance In this survey study of OHNS experts, a modified OHNS Clavien-Dindo Classification was developed and validated using case vignettes. The modified Clavien-Dindo Classification provided a granular subcategorization for each complication category and grade, duration of harm, and an overall summary complication score (CCI). Results suggest the modified OHNS Clavien-Dindo Classification reliably differentiated between high-grade and low-grade OHNS complications and could be utilized for assessing surgical outcomes.

ABSTRACT As artificial intelligence (AI) continues to rapidly reshape health care, there is a critical need for clear frameworks for clinicians to ensure ethical, equitable, and effective integration and use of AI in patient care. Key integrations of AI include enhancing health communications, patient engagement, clinicians' training, pharmaceutical advertising, clinical decision‐making, and automation of clinical operations and workflow. However, there are growing concerns related to regulatory gaps, the spread of misinformation, security threats, patient and data privacy leaks, and widening health disparities gaps. These concerns are exacerbated by limited institutional infrastructure and limited AI literacy of clinicians and patients. Recent policy developments reflect efforts to guide responsible AI development and use. While progress has been made, the lack of standardized human oversight remains a critical gap, particularly as policies may not fully consider the challenges and complexities at institutional, societal, technical, and individual levels. Thus, herein, the Drug Information Practice and Research Network (DI PRN) of the American College of Clinical Pharmacy (ACCP) : (1) explores current and emerging multifaceted challenges, a call to action, and opportunities of AI integration in health care including examination of the regulatory, ethical, operational, and health equity implications; and (2) provides practical recommendations for responsible use of AI through DI PRN‐developed example case‐based approaches and best practices infographics to enhance AI literacy for diverse learners including clinicians, trainees, and patients. This DI PRN opinion paper highlights the importance of proactive governance frameworks and equips and empowers diverse learners with practical AI literacy tools to confidently engage with AI technologies in patient care.