Citations

Using 32 immune cell surface markers, we identified 23 monocyte clusters in murine blood. Diabetic gastroparesis was associated with a significant decrease in two circulating classical monocyte-like clusters and an upregulation of the Ccr2-Ccl2 axis in the gastric muscularis propria, suggesting increased tissue monocyte migration. This study offers new targets by pointing to a possible role for two classical monocyte subsets connected to the Ccr2- Ccl2 axis.

Abstract The aging process is universal, and it is characterized by a progressive deterioration and decrease in physiological function leading to decline on the organismal level. Nevertheless, a number of genetic and nongenetic interventions have been described, which successfully extend healthspan and lifespan in different species. Furthermore, a number of clinical trials have been evaluating the feasibility of different interventions to promote human health. The goal of the annual Biological Sciences Section of the Gerontological Society of America meeting was to share current knowledge of different topics in aging research and provide a vision of the future of aging research. The meeting gathered international experts in diverse areas of aging research including basic biology, demography, and clinical and translational studies. Specific topics included metabolism, inflammaging, epigenetic clocks, frailty, senescence, neuroscience, stem cells, reproductive aging, inter-organelle crosstalk, comparative transcriptomics of longevity, circadian clock, metabolomics, and biodemography.

Silver foam dressings have been extensively used in the management of burn injuries; however, its application in children requires elucidation. A literature search was conducted from database inception to October 2023. Eligible studies reported paediatrics patients under 21 years of age receiving silver dressings for burns or scalds. This review was registered prospectively with PROSPERO (CRD42023470239). 18 studies met the inclusion criteria with a total of 701 patients. The pooled mean time to re-epithelisation (TTRE) was 12.9 days (95% CI: 11.2, 14.6, I2 = 94%). The pooled mean duration of hospitalisation was 9.8 days (95% CI: 3.9, 15.7; I2 = 100%). Mean number of total dressing changes per patient was 3.6 (95% CI: 2.2, 4.9; I2 = 99%). There were a total of 98 complications, including 30 (30.6%) infections, 29 (29.6%) surgical requirements, 14 (14.3%) hypertrophic scarring, 17 (17.3%) escalations of care, 5 (5.1%) burn depth progression, and 3 (3.1%) others. Silver foam dressings appear as a safe and effective approach in terms of healing rate and dressing change frequency for selected paediatric patients with burn injuries. Despite the promising results, further comparative studies are required to evaluate the selection criteria and long-term effect of silver foam dressing.

Importance Eligibility criteria for randomized clinical trials (RCTs) are designed to select clinically relevant patient populations. However, not all eligibility criteria are strongly justified, potentially excluding marginalized groups, and limiting the generalizability of trial findings. Objective To summarize and evaluate the justification of exclusion criteria in published RCTs in critical care medicine. Evidence Review A systematic sampling review of parallel-group RCTs published in the top 5 general internal medicine journals by impact factor ( The Lancet, New England Journal of Medicine, Journal of the American Medical Association, British Medical Journal, and Annals of Internal Medicine ) between January 1, 2018, and February 23, 2023, was conducted. RCTs enrolling adults in intensive care units (ICUs) and RCTs enrolling critically ill patients who required life-sustaining interventions typically initiated in the ICU were included. All study exclusion criteria were categorized as either poorly justified, potentially justified, or strongly justified, adapting previously established criteria, independently and in duplicate. Findings In total, 225 studies were identified, 75 of which were included. The median (IQR) number of exclusion criteria per trial was 19 (14-24), with 1455 total exclusion criteria. Common exclusion criteria were related to the risk of adverse reaction to interventions (302 criteria [20.8%]), followed by inability to obtain consent (120 criteria [8.2%]), and treatment limitation decisions (97 criteria [6.7%]). Most exclusion criteria were either strongly justified (1080 criteria [74.2%]) or potentially justified (297 criteria [20.4%]), whereas 5.4% (78 criteria) were poorly justified. Of the 78 poorly justified exclusion criteria, the most common were pregnancy (19 criteria [24.4%]), communication barriers (11 criteria [14.1%]), lactation (10 criteria [12.8%]), and lack of health insurance (10 criteria [12.8%]). Overall, 45 of 75 studies (60.0%) had at least 1 poorly justified exclusion criteria. Conclusions and Relevance Most exclusion criteria in critical care medicine RCTs were strongly justifiable. Across poorly justified criteria, the most common exclusions were pregnant or lactating persons, those with communication barriers, and individuals without health insurance. This highlights the need to carefully consider exclusion criteria when designing trials to minimize the inappropriate exclusion of participants and enhance generalizability.

AbstractBackgroundIndividuals with spinal cord injury (SCI) commonly have autonomic dysreflexia (AD) with increased sympathetic activity. After SCI, individuals have decreased baroreflex sensitivity and increased vascular responsiveness.ObjectiveTo evaluate the relationship between baroreflex and blood vessel sensitivity with AD symptoms.DesignCase control.SettingTertiary academic center.Patients14 individuals with SCI, 17 matched uninjured controls.InterventionsAll participants quantified AD symptoms using the Autonomic Dysfunction Following SCI (ADFSCI)‐AD survey. Participants received three intravenous phenylephrine boluses, reproducibly increasing systolic blood pressure (SBP) 15–40 mmHg. Continuous heart rate (R‐R interval, ECG), beat‐to‐beat blood pressures (Finapres), and popliteal artery flow velocity were recorded. Vascular responsiveness (α1 adrenoreceptor sensitivity) and heart rate responsiveness to increased SBP (baroreflex sensitivity) were calculated.Main Outcome MeasuresBaroreflex sensitivity after increased SBP; Vascular responsiveness through quantified mean arterial pressure (MAP) 2‐minute area under the curve and change in vascular resistance.ResultsSCI and control cohorts were well matched with mean age 31.9 and 29.6 years (p = .41); 21.4% and 17.6% female, respectively. Baseline MAP (p = .83) and R‐R interval (p = .39) were similar. ADFSCI‐AD scores were higher following SCI (27.9 ± 22.9 vs. 4.2 ± 2.9 in controls, p = .002). To quantify SBP response, MAP area under the curve was normalized to dose/body weight. Individuals with SCI had significantly larger responses (0.26 ± 0.19 mmHg*s/kg*μg) than controls (0.06 ± 0.06 mmHg*s/kg*μg, p = .002). Similarly, leg vascular resistance increased after SCI (24% vs. 6% to a normalized dose, p = .007). Baroreflex sensitivity was significantly lower after SCI (15.0 ± 8.3 vs. 23.7 ± 9.3 ms/mmHg, p = .01). ADFSCI‐AD subscore had no meaningful correlation with vascular responsiveness (R2 = 0.008) or baroreflex sensitivity (R2 = 0.092) after SCI.ConclusionsAlthough this confirms smaller previous studies suggesting increased α1 adrenoreceptor sensitivity and lower baroreflex sensitivity in individuals with SCI, contrary to our hypothesis these differences lacked correlation to increased symptoms of AD. Further research into physiologic mechanisms is needed to explain why some individuals with SCI develop symptoms.

ABSTRACT Nowadays, consent to use donor bodies for medical education and research is obtained from the body donors and their families before the donation. Recently, the International Federation of Associations of Anatomists (IFAA) published guidelines that could restrict the appearance of cadaveric images in commercial anatomical resources such as textbooks and other educational products. These guidelines state that the donor must expressly consent to using such images for this purpose. Cadaveric photos and drawings made from dissections of cadavers have been used in anatomy textbooks and atlases for hundreds of years. They are invaluable for anatomy students and clinical/surgical practitioners. The IFAA guidelines should not restrict the use of those older books; to do so would infringe the rights of those seeking knowledge from these resources. As the images in such textbooks and atlases are anonymized and are used for teaching and research, and the donors and their families are informed about this before the donation, we believe no additional consent is needed. It is impossible to separate educational from “commercial” usage entirely in any situation, e.g., publications from publishers and the use of cadavers in medical schools. Therefore, our best efforts to avoid unethical use of cadaveric images by following traditional consent processes are still needed so that more people will reap the benefits from them. As senior textbook/atlas authors/editors from over 10 countries, we believe that using cadaveric images in anatomy textbooks is appropriate, and no additional consent should be necessary. Such usage falls within the good faith of professionals using these invaluable gifts.

Abstract Pharmacogenomics (PGx) is focused on the relationship between an individual's genetic makeup and their response to medications, with the overarching aim of guiding prescribing decisions to improve drug efficacy and reduce adverse events. The PGx and genomic medicine communities have worked independently for over 2 decades, developing separate standards and terminology, making implementation of PGx across all areas of genomic medicine difficult. To address this issue, the Clinical Genome Resource (ClinGen) Pharmacogenomics Working Group (PGxWG) was established by the National Institutes of Health (NIH)-funded ClinGen to initially create frameworks for evaluating gene–drug response clinical validity and actionability aligned with the ClinGen frameworks for evaluating monogenic gene–disease relationships, and a framework for classifying germline PGx variants similar to the American College of Medical Genetics (ACMG) and Association of Molecular Pathology (AMP) system for interpretation of disease-causing variants. These frameworks will leverage decades of work from well-established PGx resources facilitating buy-in among PGx stakeholders. In this report, we describe the background and major activities of the ClinGen PGxWG, and how this initiative will facilitate the critical inclusion of PGx into the larger context of genomic medicine.

Abstract Background While serial sampling of glioma tissue is rarely performed prior to recurrence, cerebrospinal fluid (CSF) is an underutilized longitudinal source of candidate glioma biomarkers for understanding therapeutic impacts. However, the impact of key variables to consider in longitudinal CSF samples for monitoring biomarker discovery, including anatomical location and post-surgical changes, remains unknown. Methods Aptamer-based proteomics was performed on 147 CSF samples from 74 patients; 71 of whom had grade 2–4 astrocytomas or grade 2–3 oligodendrogliomas. This included pre- versus post-resection intracranial CSF samples obtained at early (1–16 days; n = 20 patients) or delayed (86–153 days; n = 11 patients) time points for patients with glioma. Paired lumbar versus intracranial glioma CSF samples were also obtained (n = 14 patients). Results Significant differences were identified in the CSF proteome between lumbar, subarachnoid, and ventricular CSF in patients with gliomas. Importantly, we found that resection had a significant, evolving longitudinal impact on the CSF proteome, with distinct sets of proteins present at different time points since resection. Our analysis of serial intracranial CSF samples suggests the early potential for disease monitoring and evaluation of pharmacodynamic impact of targeted therapies, such as bevacizumab and immunotherapies. Conclusions The intracranial glioma CSF proteome serves as a rich and dynamic reservoir of potential biomarkers that can be used to evaluate the effects of resection and other therapies over time. All data within this study, including detailed individual clinical annotations, are shared as a resource for the neuro-oncology community to collectively address these unanswered questions and further understand glioma biology through CSF proteomics.

Abstract Cerebrospinal fluid (CSF) has emerged as a valuable liquid biopsy source for glioma biomarker discovery and validation. CSF produced within the ventricles circulates through the subarachnoid space, where the composition of glioma-derived analytes is influenced by the proximity and anatomical location of sampling relative to tumor, in addition to underlying tumor biology. The substantial gradients observed between lumbar and intracranial CSF compartments for tumor-derived analytes underscore the importance of sampling site selection. Moreover, radiographic features, such as tumor-CSF contact and blood-brain barrier disruption, are critical covariates that may affect biomarker detection and the abundance of plasma-derived analytes in CSF, respectively. Longitudinal intracranial CSF sampling, enabled by access devices like Ommaya reservoirs, may offer a window into treatment response and disease progression, though variability in analyte yield, sample volumes, and the dynamic effects of surgical resection pose challenges. This review critically evaluates the anatomic, radiographic, and longitudinal factors, or “time-space continuum,” that impact glioma CSF biomarker abundance. Practical considerations for longitudinal CSF biobanking, including access device placement and collection, are also reviewed. Key takeaways and recommendations for CSF glioma biomarker discovery and validation are provided as a “hitchhiker’s guide” based on our collective experience, along with resources for investigators aiming to develop CSF biobanking at their institutions.