Search

The hexosamine biosynthetic pathway (HBP) generates the substrate for the O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins. The HBP also serves as a stress sensor and has been reported to be involved with nuclear factor of activated T-cells (NFAT) activation, which can contribute to multiple cellular processes including cell metabolism, proliferation, and inflammation. In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Here, we demonstrate that FGF23 increased the O-GlcNAc modification of proteins in HBECs. Furthermore, the increase in O-GlcNAc levels by FGF23 stimulation resulted in the downstream activation of NFAT and secretion of interleukin-6 (IL-6). Conversely, inhibition of FGF23 signaling and/or O-GlcNAc transferase (OGT)/O-GlcNAc reversed these effects. Collectively, these data suggest that FGF23 induced IL-6 upregulation and secretion is, at least, partially mediated via the activation of the HBP and O-GlcNAc levels in HBECs. These findings identify a novel link whereby FGF23 and the augmentation of O-GlcNAc levels regulate airway inflammation through NFAT activation and IL-6 upregulation in HBECs. The crosstalk between these signaling pathways may contribute to the pathogenesis of chronic inflammatory airway diseases such as COPD and CF as well as metabolic syndromes, including diabetes.

Computed Tomography (CT) with myelogram is a relatively safe procedure. It requires the use of nonionic contrast agents which, unlike ionic contrast agents, have been associated with low complication rates. We report a case of a 69-year-old female who developed diffuse bilateral cerebral edema following a lumber myelogram with the use of intrathecal nonionic contrast agent Omnipaque (Iohexol) 300. We were able to find one other reported case of cerebral edema following the use of intrathecal nonionic contrast agent in the literature.

https://doi.org/10.15447/sfews.2017v15iss2art5Delta Smelt have collapsed demographically, but little is known about their current genetic status. We used 12 microsatellite loci to evaluate two measures of the effective population size (Ne) of Delta Smelt. Ne is a measure that offers predictive power regarding the loss of genetic diversity in a population over time, as well as the short and long-term genetic risks for loss of fitness resulting from low diversity. We found that the Ne of Delta Smelt is too high to accurately estimate with the data (upper 95% confidence intervals were infinity), but the lower confidence intervals of NeLD (linkage disequilibrium Ne) were above 1,000, while some of the lower confidence intervals of NeV (variance Ne) were below 1,000. We interpret this to indicate that Delta Smelt are not declining because of genetic factors, and are not at immediate risk of losing genetic diversity from low Ne. We caution that these estimates are from a short-term data set estimated from a population that has already been declining for decades, and that it is likely that Delta Smelt have lost diversity. We suggest continuing efforts to maximize abundance to prevent further loss of genetic diversity.

Unlocking the full potential of pathology data by gaining computational access to histological pixel data and metadata (digital pathology) is one of the key promises of computational pathology. Despite scientific progress and several regulatory approvals for primary diagnosis using whole-slide imaging, true clinical adoption at scale is slower than anticipated. In the U.S., advances in digital pathology are often siloed pursuits by individual stakeholders, and to our knowledge, there has not been a systematic approach to advance the field through a regulatory science initiative. The Alliance for Digital Pathology ( the Alliance) is a recently established, volunteer, collaborative, regulatory science initiative to standardize digital pathology processes to speed up innovation to patients. The purpose is: (1) to account for the patient perspective by including patient advocacy; (2) to investigate and develop methods and tools for the evaluation of effectiveness, safety, and quality to specify risks and benefits in the precompetitive phase; (3) to help strategize the sequence of clinically meaningful deliverables; (4) to encourage and streamline the development of ground-truth data sets for machine learning model development and validation; and (5) to clarify regulatory pathways by investigating relevant regulatory science questions. The Alliance accepts participation from all stakeholders, and we solicit clinically relevant proposals that will benefit the field at large. The initiative will dissolve once a clinical, interoperable, modularized, integrated solution (from tissue acquisition to diagnostic algorithm) has been implemented. In times of rapidly evolving discoveries, scientific input from subject-matter experts is one essential element to inform regulatory guidance and decision-making. The Alliance aims to establish and promote synergistic regulatory science efforts that will leverage diverse inputs to move digital pathology forward and ultimately improve patient care.

Environmental DNA (eDNA) is an emerging sampling method that has been used successfully for detection of rare aquatic species. The Identification of sampling tools that are less stressful for target organisms has become increasingly important for rare and endangered species. A decline in abundance of the Southern Distinct Population Segment (DPS) of North American Green Sturgeon located in California's Central Valley has led to its listing as Threatened under the Federal Endangered Species Act in 2006. While visual surveys of spawning Green Sturgeon in the Central Valley are effective at monitoring fish densities in concentrated pool habitats, results do not scale well to the watershed level, providing limited spatial and temporal context. Unlike most traditional survey methods, environmental DNA analysis provides a relatively quick, inexpensive tool that could efficiently monitor the presence and distribution of aquatic species. We positively identified Green Sturgeon DNA at two locations of known presence in the Sacramento River, proving that eDNA can be effective for monitoring the presence of adult sturgeon. While further study is needed to understand uncertainties of the sampling method, our study represents the first documented detection of Green Sturgeon eDNA, indicating that eDNA analysis could provide a new tool for monitoring Green Sturgeon distribution in the Central Valley, complimenting traditional on-going survey methods.

Background. Due to anatomical proximity to bone, the radial nerve is the most frequently injured major nerve of the upper extremity, frequently secondary to fractures (Li et al. (2013)). We describe an incidence when a branch of the radial nerve is injured as a result of a thermal injury. Observation. Radial nerve injury can occur anywhere along the anatomical course with varied etiologies, but commonly related to trauma. The most frequent site is in the proximal forearm involving the posterior interosseous branch. However, problems can occur at the junction of the middle and proximal thirds of the humerus and wrist radially. When the radial nerve is injured by a burn, a new rehabilitation dynamic arises. Not only does one agonize about the return of nerve function but also fret about the skin grafts that replaced the devitalized tissue housing that compartment. Discussion. Although posterior interosseous nerve syndrome has been described in the context of many different etiologies, it has not previously been discussed in relation to burn injuries. In this case, not only did the patient’s rehabilitation involve aggressive therapy for return of sensation and function of the arm, but also prevention of contracture normally seen in replacement of full thickness burns.

The eastern migratory population of monarch butterflies ( Danaus plexippus plexippus ) has declined by >80% within the last two decades. One possible cause of this decline is the loss of ≥1.3 billion stems of milkweed ( Asclepias spp.), which monarchs require for reproduction. In an effort to restore monarchs to a population goal established by the US Fish and Wildlife Service and adopted by Mexico, Canada, and the US, we developed scenarios for amending the Midwestern US landscape with milkweed. Scenarios for milkweed restoration were developed for protected area grasslands, Conservation Reserve Program land, powerline, rail and roadside rights of way, urban/suburban lands, and land in agricultural production. Agricultural land was further divided into productive and marginal cropland. We elicited expert opinion as to the biological potential (in stems per acre) for lands in these individual sectors to support milkweed restoration and the likely adoption (probability) of management practices necessary for affecting restoration. Sixteen of 218 scenarios we developed for restoring milkweed to the Midwestern US were at levels (>1.3 billion new stems) necessary to reach the monarch population goal. One of these scenarios would convert all marginal agriculture to conserved status. The other 15 scenarios converted half of marginal agriculture (730 million stems), with remaining stems contributed by other societal sectors. Scenarios without substantive agricultural participation were insufficient for attaining the population goal. Agricultural lands are essential to reaching restoration targets because they occupy 77% of all potential monarch habitat. Barring fundamental changes to policy, innovative application of economic tools such as habitat exchanges may provide sufficient resources to tip the balance of the agro-ecological landscape toward a setting conducive to both robust agricultural production and reduced imperilment of the migratory monarch butterfly.

Abstract: The aim of our study was to analyze the potential survival benefit associated with hematopoietic stem cell transplantation (HSCT) according to clinicobiological scores, which incorporate mutation-enhanced international prognostic score system (MIPSS) to facilitate decision-making in this context. One transplant (n = 241) and 1 nontransplant cohort (n = 239) were used to test the hypothesis that patients with primary myelofibrosis with higher risk molecular score benefit from HSCT. A weighted propensity score was applied to balance confounding factors with the transplanted cohort as reference. Weighted Cox proportional hazard models and logistic regression analyses were performed. Overall, 105 patients who did not receive transplant could be matched to the 239 patients who did receive transplants. HSCT was associated with a higher 6-year overall survival rate in intermediate-2 (60.1% vs 41.5%) and high-risk DIPSS patients (44.4% vs 6.55%), high-risk MIPSS70 (46.5% vs 23.9%), high-risk (73.2% vs 39.7%) or very high-risk MIPSS70+V2 (51.8% vs 24%). Patients with intermediate MIPSS70 scores have an advantage of survival with HSCT only when their myelofibrosis transplant scoring system (MTSS) were low or intermediate. Patients who received transplant had an increased mortality risk the first year, but a significant benefit with HSCT after the 1-year landmark was observed in higher risk patients. This study confirms that, similar to DIPSS, MIPSS70 and MIPSS70+V2 risk score in addition to MTSS can be used to determine which patients with primary myelofibrosis have survival benefit from HSCT over non-HSCT strategies., (© 2025 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Although Vancouver B2 periprosthetic fractures (PPFs) have been historically managed with revision total hip arthroplasty (rTHA), open reduction and internal fixation (ORIF) has been proposed as an alternative option for reasons including lower cost and surgical time. The purpose of this study was to, therefore, create a Markov model to assess the cost effectiveness of ORIF versus rTHA for Vancouver B2 periprosthetic femur fractures and evaluate various inflection points for varying costs and outcome measures., Methods: A Markov model was built using discrete and mutually exclusive health states of the hypothetical patient with Vancouver B2 PPF. A decision tree was created on possible outcomes for each health state, using probabilities defined in the recent PPF literature. Direct costs and quality-adjusted life-years for each surgery and complication state were also collected. One-way and two-way deterministic sensitivity analyses were conducted to better understand the effect of 1 to 2 variables on the incremental cost-effectiveness ratio., Results: The hypothetical patient with a Vancouver B2 PPF that was treated with rTHA incurred a cost of $52,559.64 with an effectiveness of 0.71. When treated with ORIF, the cost was $47,371.97 with an effectiveness of 0.38. The incremental cost and effectiveness of rTHA over ORIF were found to be $5,187.67 and 0.33, respectively. The cost of rTHA, the cost of ORIF, and the effectiveness of ORIF were the most influential variables in the model. On two-way sensitivity analysis, rTHA was more cost effective than ORIF within realistic healthcare parameters., Discussion: From the payer perspective, we estimate that rTHA is more cost effective than ORIF for the treatment of Vancouver B2 PPFs within certain cost and quality-of-life parameters., Competing Interests: Melnic or an immediate family member serves as a paid consultant to Smith & Nephew; and has received research or institutional support from Zimmer Biomet. Bedair or an immediate family member has received royalties from Exactech, Smith & Nephew, Wolters Kluwer; serves as a paid consultant to Exactech and Smith & Nephew; has stock or stock options held in Exactech; and has received research or institutional support from Zimmer Biomet. These conflicts of interest are stated here but are unrelated to the present study. None of the following authors or any immediate family member has received anything of value from or has stock or stock options held in a commercial company or institution related directly or indirectly to the subject of this article: Scott, Blackburn, Prasad, Lim, and Lavoie-Gagne., (Copyright © 2025 by the American Academy of Orthopaedic Surgeons.)

Background: A patient's decision-making process to undergo surgery is crucial for surgeons to understand for patient-counseling purposes. Total knee and hip arthroplasty, like any other major surgery, is associated with serious, sometimes life-threatening, complications. Using the results of discrete choice experiments (DCEs), we aimed to understand the relationship between a patient's risk tolerance and choosing to undergo surgery in real life., Methods: This is a retrospective study of prospectively collected DCE results for 142 potential knee or hip arthroplasty clinic patients from October 2021 to March 2022. The DCE presented the patient with 2 scenarios, each of which was made up of different combinations of attributes and levels. A hierarchal Bayesian model was used to obtain a risk score that reflected the risk attributes chosen by each patient. Logistic regressions were then used to evaluate the association between a patient's willingness to incur risk and their decision to undergo a total joint arthroplasty., Results: Of the 142 patients enrolled in the DCE, 89 (62.3%) underwent a total joint arthroplasty. Risk score (odds ratio [OR] = 2.6, 95% confidence interval [CI] 1.1 to 6.6, P = 0.04), men (OR = 2.5, 95% CI 1.1 to 5.9, P = 0.028), and patients who have hip osteoarthritis (OR = 2.4, 95% CI 1.1 to 5.5, P = 0.036) increased the odds of undergoing arthroplasty, whereas physical function of at least 75% at the initial visit (OR = 0.3, 95% CI 0.1 to 0.7, P = 0.004) decreased these odds., Conclusions: We found that a patient's willingness to incur risk, lower baseline physical function, and men were all independently associated with undergoing total knee arthroplasty. We believe that these findings prompt much-needed future studies that focus solely on the relationship between patients' inherent risk behavior and surgical and patient-reported outcomes., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To describe characteristics associated with survival for pediatric patients with an oncologic diagnosis or hematopoietic cell transplant (HCT) supported with extracorporeal membrane oxygenation (ECMO)., Design: Multicenter, retrospective study., Setting: Sixteen PICUs in the United States and Israel., Patients: We included patients aged younger than 19 years with an oncologic diagnosis or HCT who required ECMO support between 2009 and 2021., Interventions: None., Measurements and Main Results: A total of 149 patients were included in the study cohort. There were 118 patients with an oncologic diagnosis and 31 that received HCT. The indications for ECMO were respiratory failure (46%), combined respiratory and cardiac failure (28%), and cardiac failure (25%). Venovenous (V-V) ECMO was used in 45% of patients, with 53% of patients being placed on venoarterial (V-A) ECMO. For oncologic and HCT groups, survival to ECMO decannulation was 52% (62/118) and 64% (20/31), and survival to hospital discharge was 36% (43/118) and 42% (13/31), respectively. After adjusting for other factors, requiring cardiopulmonary resuscitation was associated with greater odds ratio of mortality (3.0 [95% CI, 1.2-7.7])., Conclusions: Survival to ECMO decannulation of pediatric oncologic and HCT patients in this study was 52-64%, depending upon diagnosis. However, survival to hospital discharge remains poor. Future research should prioritize understanding factors contributing to this survival gap within these patient populations., Competing Interests: Dr. Mowrer received funding from the Extracorporeal Life Support Organization (ELSO). Drs. Nair and Potera’s institutions received funding from ELSO. Dr. Li disclosed work for hire. Dr. Barbaro’s institution received funding from the National Institutes of Health (NIH) (R01 HL153519); they disclosed they are a member of the ELSO Board of Directors and a member of pediatric extracorporeal membrane oxygenation (ECMO); they disclosed off-label use of ECMO. Dr. Barbaro is a board member for the ELSO and reports funding from the NIH (R01 HL153519). Dr. Zinter received support for article research from the NIH. Dr. Nkwantabisa received funding from Medtronic. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: The existing literature is conflicted on whether nasal deviation is primarily attributable to trauma or the result of asymmetric facial development., Objectives: The aim of this study was to establish the prevalence of nasal trauma and facial asymmetry in patients undergoing rhinoplasty, and to determine if a correlation exists between the laterality of facial asymmetry and nasal deviation., Methods: A retrospective review was undertaken of patients who had undergone primary rhinoplasty with the senior author over a 12-month period. Patient charts were reviewed and clinical photographs were analyzed., Results: In total, 144 patients underwent rhinoplasty over the study period; 68 patients underwent revision rhinoplasty and were excluded. Of the 76 patients who underwent primary rhinoplasty, 9% reported prior nasal trauma, 68% had deviated nasal bones, 46% had deviated nasal tips, 70% had asymmetric midfaces, and 36% had deviated chins. In patients without prior trauma history, nasal bones were most commonly deviated towards the side of midface hypoplasia (53%, P = .008). The nasal tip was most commonly deviated contralateral to the side of septal deviation (59%, P = .001). There was no association between nasal bone and chin deviation. Nasal tip deviation was not associated with midface hypoplasia or chin deviation., Conclusions: Nasal deviation is primarily driven by asymmetric facial growth rather than being the result of nasal trauma., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Aesthetic Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: To describe the construction and use of a percutaneous pelvic fixation model, evaluate its translational validity among fellowship-trained orthopedic trauma surgeons, and investigate the importance of specific criteria for effective competency-based assessment of pelvic fixation techniques., Methods: Five orthopedic trauma surgeons were asked to place percutaneous wires on a pelvic fixation model, including anterior column (antegrade/retrograde), posterior column (antegrade/retrograde), supra-acetabular, transsacral, and iliosacral. Evaluation criteria included successful wire placement, redirections, cortical breaches, procedure duration, radiation exposure, and quality of fluoroscopic views. Following completion, participants were provided a survey to rate the model., Results: There were no differences between approaches on successful screw placement, wire redirections, or fluoroscopic quality. Antegrade approaches to the anterior and posterior columns took longer (p = 0.008) and used more radiation (p = 0.02). There was also a trend toward more cortical breaches with the antegrade anterior column approach (p = 0.07). Median ratings among surgeons were 4 out of 5 for their overall impression and its accuracy in tactile response, positioning constraints, and fluoroscopic projections. Learning parameters considered most important to the progression of trainees (most to least important) were successful screw placement, corridor breaches, wire redirections, quality of fluoroscopic views, radiation exposure, and procedure duration., Conclusion: In being affordable, accessible, and realistic, this percutaneous pelvic fixation model represents an opportunity to advance orthopedic surgery education globally. Future research is needed to validate the findings of this pilot study and to expand upon how trainees should be evaluated within simulations and the operating room to optimize skill progression., (© 2023. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Purpose: Rami comminution has been found to be predictive of lateral compression type 1 (LC1) injury instability on examination under anesthesia (EUA) and lateral stress radiographs (LSR). The purpose of this study was to evaluate how rami comminution and subsequent operative vs. nonoperative management impact the late displacement of these injuries., Methods: Retrospective review of a prospectively collected LC1 database was performed to identify all patients with minimally displaced LC1 injuries (< 1 cm) and follow-up radiographs over a four-year period (n = 125). Groups were separated based on the presence of rami comminution and subsequent management, including rami comminution/operative (n = 49), rami comminution/nonoperative (n = 54), and no comminution/nonoperative (control group, n = 22). The primary outcome was late fracture displacement, analyzed as both a continuous variable and as late displacement ≥ 5 mm., Results: As a continuous variable, late fracture displacement was lower in the comminuted rami/operative group as compared to the comminuted rami/nonoperative group (PD: -3.0 mm, CI: -4.8 to -1.6 mm, p = 0.0002) and statistically non-different from control. Late displacement ≥ 5 mm was significantly more prevalent in the comminuted rami/nonoperative group than in the comminuted rami/operative and no comminution/nonoperative groups (control)(PD: -33.9%, CI: -49.0% to -16.1%, p = 0.0002 and PD: -30.0%, CI: -48.2% to -6.5%, p = 0.02, respectively)., Conclusion: Late fracture displacement was greatest in the group with rami comminution/nonoperative management. Rami comminution, which has been previously associated with dynamic displacement on EUA and LSR, is also associated with a higher incidence of late displacement when managed nonoperatively., Level of Evidence: Level III, prognostic retrospective cohort study., (© 2023. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Despite the discovery of actinide borohydride complexes over 80 years ago, no plutonium borohydride complexes have been structurally validated using single-crystal X-ray diffraction (XRD). Here we describe Pu 2 (H 3 BP t Bu 2 BH 3 ) 6 , the first example of a Pu(III) borohydride complex authenticated by XRD and NMR spectroscopy. Theoretical calculations (DFT, EDA, and QTAIM) and experimental comparisons of metal-boron distances suggest that metal-borohydride covalency in M 2 (H 3 BP t Bu 2 BH 3 ) 6 complexes generally decreases in the order M = U(III) > Pu(III) > Ln(III).

Abstract: Severe aplastic anemia (SAA) is a rare hematologic condition for which there is no clear management algorithm. A panel of 11 experts on adult and pediatric aplastic anemia was assembled and, using the RAND/University of California, Los Angeles modified Delphi panel method, evaluated >600 varying patient care scenarios to develop clinical recommendations for the initial and subsequent management of patients of all ages with SAA. Here, we present the panel's recommendations to rule out inherited bone marrow failure syndromes, on supportive care before and during first-line therapy, and on first-line (initial management) and second-line (subsequent management) therapy of acquired SAA, focusing on when transplant vs medical therapy is most appropriate. These recommendations represent the consensus of 11 experts informed by published literature and experience. They are intended only as general guidance for experienced clinicians who treat patients with SAA and are in no way intended to supersede individual physician and patient decision making. Current and future research should validate this consensus using clinical data. Once validated, we hope these expert panel recommendations will improve outcomes for patients with SAA., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

We report herein that the anti-CD20 therapeutic antibody, rituximab, is rearranged into microclusters within the phagocytic synapse by macrophage Fcγ receptors (FcγR) during antibody-dependent cellular phagocytosis. These microclusters were observed to potently recruit Syk and to undergo rearrangements that were limited by the cytoskeleton of the target cell, with depolymerization of target-cell actin filaments leading to modest increases in phagocytic efficiency. Total internal reflection fluorescence analysis revealed that FcγR total phosphorylation, Syk phosphorylation, and Syk recruitment were enhanced when IgG-FcγR microclustering was enabled on fluid bilayers relative to immobile bilayers in a process that required Arp2/3. We conclude that on fluid surfaces, IgG-FcγR microclustering promotes signaling through Syk that is amplified by Arp2/3-driven actin rearrangements. Thus, the surface mobility of antigens bound by IgG shapes the signaling of FcγR with an unrecognized complexity beyond the zipper and trigger models of phagocytosis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Changes in retinal structure and microvasculature are connected to parallel changes in the brain. Two recent studies described machine learning algorithms trained on retinal images and quantitative data that identified Alzheimer's dementia and mild cognitive impairment with high accuracy. Prior studies also demonstrated retinal differences in individuals with PD. Herein, we developed a convolutional neural network (CNN) to classify multimodal retinal imaging from either a Parkinson's disease (PD) or control group., Methods: We trained a CNN to receive retinal image inputs of optical coherence tomography (OCT) ganglion cell-inner plexiform layer (GC-IPL) thickness color maps, OCT angiography 6 × 6-mm en face macular images of the superficial capillary plexus, and ultra-widefield (UWF) fundus color and autofluorescence photographs to classify the retinal imaging as PD or control. The model consists of a shared pretrained VGG19 feature extractor and image-specific feature transformations which converge to a single output. Model results were assessed using receiver operating characteristic (ROC) curves and bootstrapped 95% confidence intervals for area under the ROC curve (AUC) values., Results: In total, 371 eyes of 249 control subjects and 75 eyes of 52 PD subjects were used for training, validation, and testing. Our best CNN variant achieved an AUC of 0.918. UWF color photographs were the most effective imaging input, and GC-IPL thickness maps were the least contributory., Conclusions: Using retinal images, our pilot CNN was able to identify individuals with PD and serves as a proof of concept to spur the collection of larger imaging datasets needed for clinical-grade algorithms., Translational Relevance: Developing machine learning models for automated detection of Parkinson's disease from retinal imaging could lead to earlier and more widespread diagnoses.

Acute and chronic graft-versus-host disease (GvHD) are major complications of allogeneic hematopoietic cell transplantation (alloHCT). In vivo T-cell depletion with anti-T-lymphocyte globulin (ATLG) as part of the conditioning regimen prior to alloHCT is frequently used as GvHD prophylaxis, but data on its role in myelofibrosis is scarce. We took advantage of an international collaborative network to investigate the impact of ATLG in myelofibrosis undergoing first alloHCT. We included 707 patients (n = 469 ATLG and n = 238 non-ATLG prophylaxis). The cumulative incidence of acute GvHD grade II-IV was 30% for the ATLG group vs. 56% for the non-ATLG group (P < 0.001). Acute GvHD grade III-IV occurred in 20% vs. 25%, respectively (P = 0.01). Incidence of mild-to-severe chronic GvHD was 49% vs. 50% (P = 0.52), while ATLG showed significantly lower rates of severe chronic GvHD (7% vs. 18%; P = 0.04). GvHD-free and relapse-free survival (GRFS) at 6 years was 45% for the ATLG group vs. 37% for the non-ATLG group (P = 0.02), driven by significantly improved GRFS of ATLG in matched related and matched unrelated donors. No significant differences in risk for relapse, non-relapse mortality, and overall survival were observed. Multivariable modeling for GRFS showed a 48% reduced risk of GvHD, relapse, or death when using ATLG., (© 2024. The Author(s).)

The intrinsic negative thermal expansion of UF 4 below room temperature was examined. A redetermination of the structure of UF 4 by single-crystal X-ray diffraction at 100, 200, and 300 K accompanied by an evaluation of the atomic displacement parameters (ADPs) of the F atoms was performed. The structure of UF 4 was described as the stacking of two subnetworks, respectively, constituted by the U(1) and U(2) atoms. The subnetwork formed by the U(2) atoms consists of infinite layers that run parallel to the ( b , c ) plan. The layers are composed of infinite zigzag chains of corner-sharing U(2)F 8 polyhedra running along the c -axis. An increase of temperature from 100 to 300 K leads to a decrease of the unit cell volume and the a and c lattice parameters and an increase of the b lattice parameter. As the temperature increases, the intrachain, interchain, and interlayer U-U distances decrease. It is proposed that the decrease of the intrachain and interlayer U-U distances causes a contraction of the U(2) subnetwork along the a - and c -axis and that a translation of the chains along the c -axis causes an expansion along the b -axis. Analysis of the ADPs of the F atoms indicates that a guitar string effect in the U-F-U units is possibly the origin of the decrease in the U-U distances. A correlation between the U-U distances and the magnitude of the ADPs of the F atoms was established., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Outcomes for adults with relapsed/refractory (R/R) high-grade myeloid neoplasms remain poor, with allogeneic hematopoietic cell transplantation (HCT) the sole therapy likely to result in cure. We conducted the present study to determine the feasibility of early HCT-within 60 days of beginning reinduction chemotherapy-to see whether getting patients to HCT in an expeditious manner would expand the number of patients being offered this curative option. In this proof-of-principle feasibility study, we included adults age 18 to 75 years with R/R myeloid malignancies with ≥10% blood/marrow blasts at diagnosis who were eligible for a reduced-intensity HCT. Subjects received reinduction chemotherapy with cladribine, cytarabine, mitoxantrone, and filgrastim (CLAG-M) and proceeded to HCT with reduced-intensity conditioning (fludarabine/ melphalan). We enrolled 30 subjects, all of whom received CLAG-M reinduction, although only 9 underwent HCT within 60 days (<15, the predetermined threshold for feasibility "success"), with a median time to HCT of 48 days (range, 42 to 60 days). Eleven additional subjects received HCT beyond the target 60 days (off-study), with a median time to transplantation of 83 days (range, 53 to 367 days). Barriers to early HCT included infection, physician preference, lack of an HLA-matched donor, logistical delays, and disease progression, all of which may limit the real-world uptake of such early-to-transplantation protocols., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Multiparameter flow cytometry (MFC) measurable residual disease (MRD) before allogeneic hematopoietic cell transplantation (HCT) independently predicts poor outcomes in acute myeloid leukemia (AML). Conversely, its prognostic value in the newly defined disease entity, myelodysplastic neoplasm (MDS)/AML is unknown. To assess the relationship between disease type, pre-HCT MRD, and post-HCT outcomes, we retrospectively analyzed 1265 adults with MDS/AML (n = 151) or AML (n = 1114) who received a first allograft in first or second morphologic remission at a single institution between April 2006 and March 2023. At 3 years, relapse rates (29% for MDS/AML vs. 29% for AML, p = .98), relapse-free survival (RFS; 50% vs. 55%, p = .22), overall survival (OS; 52% vs. 60%, p = .073), and non-relapse mortality (22% vs. 16%, p = .14) were not statistically significantly different. However, a significant interaction was found between pre-HCT MFC MRD and disease type (MDS/AML vs. AML) for relapse (p = .009), RFS (p = .011), and OS (p = .039). The interaction models indicated that the hazard ratios (HRs) for the association between pre-HCT MRD and post-HCT outcomes were lower in patients with MDS/AML (for relapse: HR = 1.75 [0.97-3.15] in MDS/AML vs. 4.13 [3.31-5.16] in AML; for RFS: HR = 1.58 [1.02-2.45] vs. 2.98 [2.48-3.58]; for OS: HR = 1.50 [0.96-2.35] vs. 2.52 [2.09-3.06]). On the other hand, residual cytogenetic abnormalities at the time of HCT were equally informative in MDS/AML as in AML patients. Our data indicate that MFC-based pre-HCT MRD testing, but not testing for residual cytogenetic abnormalities, is less informative for MDS/AML than AML patients when used for prognostication of post-HCT outcomes., (© 2024 Wiley Periodicals LLC.)

Splenomegaly is the clinical hallmark of myelofibrosis. Splenomegaly at the time of allogeneic hematopoietic cell transplantation (HCT) is associated with graft failure and poor graft function. Strategies to reduce spleen size before HCT especially after failure to Janus kinase (JAK) inhibition represent unmet clinical needs in the field. Here, we leveraged a global collaboration to investigate the safety and efficacy of splenic irradiation as part of the HCT platform for patients with myelofibrosis. We included 59 patients, receiving irradiation within a median of 2 weeks (range, 0.9-12 weeks) before HCT. Overall, the median spleen size prior to irradiation was 23 cm (range, 14-35). Splenic irradiation resulted in a significant and rapid spleen size reduction in 97% of patients (57/59), with a median decrease of 5.0 cm (95% confidence interval, 4.1-6.3 cm). The most frequent adverse event was thrombocytopenia, with no correlation between irradiation dose and hematological toxicities. The 3-year overall survival was 62% (95% CI, 48%-76%) and 1-year non-relapse mortality was 26% (95% CI, 14%-38%). Independent predictors for survival were severe thrombocytopenia and anemia before irradiation, transplant-specific risk score, higher-intensity conditioning, and present portal vein thrombosis. When using a propensity score matching adjusted for common confounders, splenic irradiation was associated with significantly reduced relapse (p = .01), showing a 3-year incidence of 12% for splenic irradiation versus 29% for patients with immediate HCT and 38% for patients receiving splenectomy. In conclusion, splenic irradiation immediately before HCT is a reasonable approach in patients experiencing JAK inhibition failure and is associated with a low incidence of relapse., (© 2024 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Comparison of bonding and electronic structural features between trivalent lanthanide (Ln) and actinide (An) complexes across homologous series' of molecules can provide insights into subtle and overt periodic trends. Of keen interest and debate is the extent to which the valence f- and d-orbitals of trivalent Ln/An ions engage in covalent interactions with different ligand donor functionalities and, crucially, how bonding differences change as both the Ln and An series are traversed. Synthesis and characterization (SC-XRD, NMR, UV-vis-NIR, and computational modeling) of the homologous lanthanide and actinide N-heterocyclic carbene (NHC) complexes [M(C 5 Me 5 ) 2 (X)(I Me4 )] {X = I, M = La, Ce, Pr, Nd, U, Np, Pu; X = Cl, M = Nd; X = I/Cl, M = Nd, Am; and I Me4 = [C(NMeCMe) 2 ]} reveals consistently shorter An-C vs Ln-C distances that do not substantially converge upon reaching Am 3+ /Nd 3+ comparison. Specifically, the difference of 0.064(6) Å observed in the La/U pair is comparable to the 0.062(4) Å difference observed in the Nd/Am pair. Computational analyses suggest that the cause of this unusual observation is rooted in the presence of π-bonding with the valence d-orbital manifold in actinide complexes that is not present in the lanthanide congeners. This is in contrast to other documented cases of shorter An-ligand vs Ln-ligand distances, which are often attributed to increased 5f vs 4f radial diffusivity leading to differences in 4f and 5f orbital bonding involvement. Moreover, in these traditional observations, as the 5f series is traversed, the 5f manifold contracts such that by americium structural studies often find no statistically significant Am 3+ vs Nd 3+ metal-ligand bond length differences.

Purpose: BMT CTN 1102 was a phase III trial comparing reduced-intensity allogeneic hematopoietic cell transplantation (RIC alloHCT) to standard of care for persons with intermediate- or high-risk myelodysplastic syndrome (MDS). We report results of a cost-effectiveness analysis conducted alongside the clinical trial., Methods: Three hundred eighty-four patients received HCT (n = 260) or standard of care (n = 124) according to availability of a human leukocyte antigen-matched donor. Cost-effectiveness was calculated from US commercial and Medicare perspectives over a 20-year time horizon. Health care utilization and costs were estimated using propensity score-matched cohorts of HCT recipients in the OptumLabs Data Warehouse (age 50-64 years) and Medicare (age 65 years and older). EuroQol 5 Dimension (EQ-5D) surveys of trial participants were used to derive health state utilities., Results: Extrapolated 20-year overall survival for those age 50-64 years was 29% for HCT (n = 105) versus 13% for usual care (n = 44) and 31% for HCT (n = 155) versus 12% for non-HCT (n = 80) for those age 65 years and older. HCT was more effective (+2.36 quality-adjusted life-years [QALYs] for age 50-64 years and +2.92 QALYs for age 65 years and older) and more costly (+$452,242 in US dollars (USD) for age 50-64 years and +$233,214 USD for age 65 years and older) than usual care, with incremental cost-effectiveness ratios of $191,487 (USD)/QALY and $79,834 (USD)/QALY, respectively. For persons age 50-64 years, there was a 29% chance that HCT was cost-effective using a willingness-to-pay (WTP) threshold of $150K (USD)/QALY and 51% at a $200K (USD)/QALY. For persons age 65 years and older, the probability was 100% at a WTP >$150K (USD)/QALY., Conclusion: Among patients age 65 years and older with high-risk MDS, RIC HCT is a high-value strategy. For those age 50-64 years, HCT is a lower-value strategy but has similar cost-effectiveness to other therapies commonly used in oncology.

Organoplutonium chemistry was established in 1965, yet structurally authenticated plutonium-carbon bonds remain rare being limited to π-bonded carbocycle and σ-bonded isonitrile and hydrocarbyl derivatives. Thus, plutonium-carbenes, including alkylidenes and N-heterocyclic carbenes (NHCs), are unknown. Here, we report the preparation and characterization of the diphosphoniomethanide-plutonium complex [Pu(BIPM TMS H)(I)(μ-I)] 2 ( 1Pu , BIPM TMS H = (Me 3 SiNPPh 2 ) 2 CH) and the diphosphonioalkylidene-plutonium complexes [Pu(BIPM TMS )(I)(DME)] ( 2Pu , BIPM TMS = (Me 3 SiNPPh 2 ) 2 C) and [Pu(BIPM TMS )(I)(I Me4 ) 2 ] ( 3Pu , I Me4 = C(NMeCMe) 2 ), thus disclosing non-actinyl transneptunium multiple bonds and transneptunium NHC complexes. These Pu-C double and dative bonds, along with cerium, praseodymium, samarium, uranium, and neptunium congeners, enable lanthanide-actinide and actinide-actinide comparisons between metals with similar ionic radii and isoelectronic 4f 5 vs 5f 5 electron-counts within conserved ligand fields over 12 complexes. Quantum chemical calculations reveal that the orbital-energy and spatial-overlap terms increase from uranium to neptunium; however, on moving to plutonium the orbital-energy matching improves but the spatial overlap decreases. The bonding picture that emerges is more complex than the traditional picture of the bonding of lanthanides being ionic and early actinides being more covalent but becoming more ionic left to right. Multiconfigurational calculations on 2M and 3M (M = Pu, Sm) account for the considerably more complex UV/vis/NIR spectra for 5f 5 2Pu and 3Pu compared to 4f 5 2Sm and 3Sm . Supporting the presence of Pu═C double bonds in 2Pu and 3Pu , 2Pu exhibits metallo-Wittig bond metathesis involving the highest atomic number element to date, reacting with benzaldehyde to produce the alkene PhC(H)═C(PPh 2 NSiMe 3 ) 2 ( 4 ) and "PuOI". In contrast, 2Ce and 2Pr do not react with benzaldehyde to produce 4 .

Objective: To characterize retinal and choroidal microvascular and structural changes in patients who are gene positive for mutant huntingtin protein (mHtt) with symptoms of Huntington's Disease (HD)., Methods: This study is a cross-sectional comparison of patients who are gene positive for mHtt and exhibit symptoms of HD, either motor manifest or prodromal (HD group), and cognitively normal individuals without a family history of HD (control group). HD patients were diagnosed by Duke movement disorder neurologists based on the Unified Huntington's Disease Rating Scale (UHDRS). Fovea and optic nerve centered OCT and OCTA images were captured using Zeiss Cirrus HD-5000 with AngioPlex. Outcome metrics included central subfield thickness (CST), peripapillary retinal nerve fiber layer (pRNFL) thickness, ganglion cell-inner plexiform layer (GCIPL) thickness, and choroidal vascularity index (CVI) on OCT, and foveal avascular zone (FAZ) area, vessel density (VD), perfusion density (PD), capillary perfusion density (CPD), and capillary flux index (CFI) on OCTA. Generalized estimating equation (GEE) models were used to account for inter-eye correlation., Results: Forty-four eyes of 23 patients in the HD group and 77 eyes of 39 patients in the control group were analyzed. Average GCIPL thickness and FAZ area were decreased in the HD group compared to controls (p = 0.001, p < 0.001). No other imaging metrics were significantly different between groups., Conclusions: Patients in the HD group had decreased GCIPL thickness and smaller FAZ area, highlighting the potential use of retinal biomarkers in detecting neurodegenerative changes in HD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Joseph et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To investigate retinal vascular characteristics using ultra-widefield (UWF) scanning laser ophthalmoscopy in Parkinson disease (PD)., Methods: Individuals with an expert-confirmed clinical diagnosis of PD and controls with normal cognition without PD underwent Optos California UWF imaging. Patients with diabetes, uncontrolled hypertension, glaucoma, dementia, other movement disorders, or known retinal or optic nerve pathology were excluded. Images were analyzed using Vasculature Assessment and Measurement Platform for Images of the Retina (VAMPIRE-UWF) software, which describes retinal vessel width gradient and tortuosity, provides vascular network fractal dimensions, and conducts alpha-shape analysis to further characterize vascular morphology (complexity, Opαmin; spread, OpA)., Results: In the PD cohort, 53 eyes of 38 subjects were assessed; in the control cohort, 51 eyes of 33 subjects were assessed. Eyes with PD had more tortuous retinal arteries in the superotemporal quadrant (P = 0.043). In eyes with PD, alpha-shape analysis revealed decreased OpA, indicating less retinal vasculature spread compared to controls (P = 0.032). Opαmin was decreased in PD (P = 0.044), suggesting increased vascular network complexity. No differences were observed in fractal dimension in any region of interest., Conclusions: This pilot study suggests that retinal vasculature assessment on UWF images using alpha-shape analysis reveals differences in retinal vascular network spread and complexity in PD and may be a more sensitive metric compared to fractal dimension., Translational Relevance: Retinal vasculature assessment using these novel methods may be useful in understanding ocular manifestations of PD and the development of retinal biomarkers.

New options for medical therapy and risk scoring systems containing molecular data are leading to increased complexity in the management of patients with myelofibrosis. To inform patients' optimal care, we updated the 2015 guidelines on indications for and management of allogeneic haematopoietic stem-cell transplantation (HSCT) with the support of the European Society for Blood and Marrow Transplantation (EBMT) and European LeukemiaNet (ELN). New recommendations were produced using a consensus-building methodology after a comprehensive review of articles released from January, 2015 to December, 2022. Seven domains and 18 key questions were selected through a series of questionnaires using a Delphi process. Key recommendations in this update include: patients with primary myelofibrosis and an intermediate-2 or high-risk Dynamic International Prognostic Scoring System score, or a high-risk Mutation-Enhanced International Prognostic Score Systems (MIPSS70 or MIPSS70-plus) score, or a low-risk or intermediate-risk Myelofibrosis Transplant Scoring System score should be considered candidates for allogeneic HSCT. All patients who are candidates for allogeneic HSCT with splenomegaly greater than 5 cm below the left costal margin or splenomegaly-related symptoms should receive a spleen-directed treatment, ideally with a JAK-inhibitor; HLA-matched sibling donors remain the preferred donor source to date. Reduced intensity conditioning and myeloablative conditioning are both valid options for patients with myelofibrosis. Regular post-transplantation driver mutation monitoring is recommended to detect and treat early relapse with donor lymphocyte infusion. In a disease where evidence-based guidance is scarce, these recommendations might help clinicians and patients in shared decision making., Competing Interests: Declaration of interests NK has received honoraria for lectures and advisory boards from Kite, Jazz, Merck Sharp & Dohme, Neovii Biotech, Alexion, Takeda, Novartis, Riemser, Pfizer, and Bristol Myers Squibb. NK has also received research support from Neovii, Riemser, Novartis, and Deutsche Knochenmarkspender Datei, and research grants from Neovii, Jazz, Celgene, and Novartis. AMV has received honoraria for lectures from Novartis, Incyte, AbbVie, GlaxoSmithKline, Bristol Myers Squibb, and AOP Orphan Pharmaceutical GmbH. CH has received honoraria for lectures from AbbVie, AOP Orphan Pharmaceutical GmbH, Bristol Myers Squibb, CTIBioPharma, Imago Biosciences, Incyte, Novartis, Galacteo, Geron, Gilead, GlaxoSmithKline, Janssen, Keros, Promedior, Roche, Shire, and Sierra. SK has received grants or contracts from AOP Orphan Pharmaceutical GmbH, Janssen, Geron, and Novartis. SK has received consulting fees from Novartis, Bristol Myers Squibb, Incyte, AOP Orphan Pharmaceutical GmbH, Baxalta, CTI Biopharma, Pfizer, Sanofi, Celgene, Shire, Janssen, Geron, Karthos, Sierra Oncology, GlaxoSmithKline, Imago Biosciences, AbbVie, and iOMEDICO. SK has received honoraria for lectures from Novartis, Bristol Myers Squibb, Pfizer, Incyte, Ariad, Shire, Roche, AOP Orphan Pharmaceutical GmbH, Janssen, Geron, Celgene, Karthos, Abbvie, iOMEDICO, and GlaxoSmithKline. SK has received payment for expert testimony from Novartis and GlaxoSmithKline. SK has received funding for travel from Alexion, Novartis, Bristol Myers Squibb, Celgene, Incyte, Ariad, AOP Orphan Pharmaceutical GmbH, CTI Biopharma, Pfizer, Sanofi, Janssen, Geron, Imago Biosciences, GlaxoSmithKline, PharmaEssentia, Sierra Oncology, AbbVie, and iOMEDICO. SK has a patent for bromodomain and extra-terminal motif inhibitors related to RWTH Aachen University (Aachen, Germany). SK has received honoraria for participation on data safety monitoring boards and advisory boards from Pfizer, Incyte, Novartis, AOP Orphan Pharmaceutical GmbH, Bristol Myers Squibb, Celgene, Geron, Janssen, CTI Biopharma, Roche, Baxalta, Sanofi, Myeloproliferative Neoplasm Hub, Sierra Oncology, GlaxoSmith Kline, AbbVie, and PharmaEssentia. SK is chairman of the Hemostasis Working Party of the German Society of Hematology and Medical Oncology, speaker of the German Study Group of the Myeloproliferative Neoplasm Hub, member of the Guidelines Committee of European Haematology Association, and an associate editor for the Hemasphere journal. DPM has received honoraria for lectures from GlaxoSmithKline, Bristol Myers Squibb, Novartis, and AbbVie. TJ has received grants from CTI Biopharma, Kartos Therapeutics, and Incyte. TJ has received honoraria for participation on advisory boards from Care Dx, Bristol Myers Squibb, Incyte, Abbvie, CTI Biopharma, Kite, Cogent Biosciences, Blueprint Medicine, Telios Pharma, and Protagonist Therapeutics. NH has received honoraria for lectures from Novartis. AR has received honoraria for lectures from Novartis, Bristol Myers Squibb, Sanofi, Abbvie, Amgen, Pfizer, Kite-Gilead, Jazz, Astellas, Incyte, and Omeros. MG has received honoraria for lectures from AOP Orphan Pharmaceutical GmbH, Novartis, Bristol Myers Squibb, AbbVie, Pfizer, Janssen, Gilead, AstraZeneca, Lilly, and GlaxoSmithKline. VG has received grants from Novartis and Incyte. VG has received consulting fees from Novartis, Incyte, Bristol Myers Squibb, Celgene, GlaxoSmithKline, CTI Biopharma, Morphosys, AbbVie, and Pfizer. VG has received honoraria for lectures from GlaxoSmithKline. VG has received funding for travel and registration fees from GlaxoSmithKline. VG is a member of the Executive Committee of the Canadian Myeloproliferative Neoplasm Group. NP has received honoraria for lectures from Novartis, Bristol-Myers Squibb, and Abbvie. NP has received funding for travel and registrations fees from Abbvie and Novartis. NP has received honoraria for participation on advisory boards from Novartis and Abbvie. JM has received grants from Incyte, Novartis, Roche, CTI Biopharma, Geron, Kartos, Karyopharm, PharmaEssentia, AbbVie, and Bristol Myers Squibb. JM has received consulting fees from Incyte, Novartis, CTI Biopharma, Geron, Kartos, Karyopharm, Bristol Myers Squibb, AbbVie, PharmaEssentia, Galecto, Imago, Merck, Pfizer, GlaxoSmithKline, and MorphoSys. MD has received honoraria for lectures from Pfizer, Merck Sharp & Dohme, and Novartis. MD has received funding for travel and registration fees from Biotest. FP has received honoraria for lectures from Novartis, Bristol Myers Squibb, Abbvie, AOP Orphan Pharmaceutical GmbH, and Janssen. FP has received honoraria for participation on advisory boards from Novartis, Bristol Myers Squibb, GlaxoSmithKline, Abbvie, AOP Orphan Pharmaceutical GmbH, Janssen, Karyiopharma, Kyowa Kirin and MEI, Sumitomo, and Kartos. TB has received honoraria for lectures from AOP Orphan Pharmaceutical GmbH, Novartis, and Pharma Essentia. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The synthesis, characterization, electrochemical performance, and theoretical modeling of two base-metal charge carrier complexes incorporating a pendent quaternary ammonium group, [Ni(bppn-Me 3 )][BF 4 ], 3' , and [Fe(PyTRENMe)][OTf] 3 , 4' , are described. Both complexes were produced in high yield and fully characterized using NMR, IR, and UV-vis spectroscopies as well as elemental analysis and single-crystal X-ray crystallography. The solubility of 3' in acetonitrile showed a 283% improvement over its neutral precursor, whereas the solubility of complex 4 ' was effectively unchanged. Cyclic voltammetry indicates an ∼0.1 V positive shift for all waves, with some changes in reversibility depending on the wave. Bulk electrochemical cycling demonstrates that both 3' and 4' can utilize the second more negative wave to a degree, whereas 4' ceases to have a reversible positive wave. Flow cell testing of 3' and 4' with Fc as the posolyte reveals little improvement to the cycling performance of 3' compared with its parent complex, whereas 4' exhibits reductions in capacity decay when cycling either negative wave. Postcycling CVs indicate that crossover is the likely source of capacity loss in complexes 3 , 3' , and 4' because there is little change in the CV trace. Density functional theory calculations indicate that the ammonium group lowers the HOMO energy in 3' and 4' , which may impart stability to cycling negative waves while making positive waves less accessible. Overall, the incorporation of a positively charged species can improve solubility, stored electron density, and capacity decay depending on the complex, features critical to high energy density redox flow battery performance.

Objectives: To evaluate the incidence of pelvic space surgical site infection (SSI) after preperitoneal pelvic packing (PPP) for persistent hemodynamic instability., Design: Retrospective comparative study., Setting: Urban Level 1 trauma center., Patients/participants: 83 patients who received PPP and 55 patients who had open reduction and internal fixation (ORIF) of the anterior pelvic ring without PPP., Intervention: Operative fixation., Main Outcome Measurements: Pelvic space SSI., Results: The SSI rate in the PPP group was 31.3% (26/83) compared with 10.9% (6/55) in the control group (proportional difference 20.4%, confidence interval (CI) 6.4-32.5, P = 0.007). Patients in the PPP group (n = 43) were 1:1 propensity score matched with patients in the control group to account for differences in Injury Severity Score and American Society of Anesthesiologists score. In this matched cohort, the rate of pelvic space SSI remained higher in the PPP group compared with that in the control group (30.2% vs. 9.3%; proportional difference 20.9%, CI, 3.7-36.3; P = 0.02). On multivariate analysis of the PPP group, anterior ORIF (odds ratio 6.56, CI, 2.00-21.47, P = 0.002) was found to be independently associated with SSI., Conclusions: PPP is an independent risk factor of space SSI. The likelihood of SSI after PPP is increased with anterior ORIF. The morbidity of SSI after PPP must be weighed against the risk of exsanguination., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)