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Introduction: Chronic limb-threatening ischemia (CLTI) represents the most severe form of peripheral artery disease. While previous studies have focused on gender and racial disparities, there is lack of evidence regarding the impact of housing status. The aim of this analysis was to identify disparities in inpatient management and outcomes of CLTI based on housing status., Methods: In this retrospective, descriptive study, we analyzed patients admitted with CLTI who underwent revascularization, as identified by ICD-10 codes, between 2016-2021, using the National Inpatient Sample database. The patients were stratified by their housing status and a detailed, propensity-matched analysis was conducted to compare the demographics, comorbidities, mortality rates, types of intervention, resource utilization, and inpatient outcomes., Results: During the study, 2,667,294 patients were admitted with CLTI, and 17% (463,435) underwent revascularization. Among these, 0.4% (1,790) were unhoused. Males were overrepresented in the unhoused group (83.5% vs. 62.5%, p<0.001). Unhoused patients were more likely to receive endovascular revascularization (AOR 1.77, 0.45-0.90, p=0.003) but less likely to undergo open surgical intervention (AOR 0.64, 0.45-0.90, p=0.010). They were also more likely to undergo aortoiliac interventions, while housed patients underwent more distal interventions. The mean adjusted length of stay was four days longer and inflation-adjusted costs were $8,501 higher for unhoused patients (p<0.001). Unhoused patients were also more likely to leave against medical advice and be transferred to skilled nursing facilities., Conclusion: This study highlights significant disparities in CLTI management and outcomes between housed and unhoused patients, underscoring the need for targeted interventions to address these inequities., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Delayed stent grafting for blunt thoracic aortic injuries (BTAI) is current standard of care. However, given the heterogeneity of pseudoaneurysm presentations, it is currently unclear which severe BTAIs require more urgent intervention. We hypothesize that a Traumatic Aortic Disruption Index (TADI) calculation based on sagittal computed tomography angiography (CTA) imaging measurements would correlate with urgency of stent grafting., Methods: All patients at a level-1 trauma center with BTAIs over a 12-year period were identified. A TADI score was then calculated using the length of pseudoaneurysm (L), maximum width of pseudoaneurysm (W), and normal adjacent aortic diameter (NA) (Figure1). Patient presentation, injury characteristics, timing of stent grafting, and outcomes were then evaluated., Results: Forty-two patients were diagnosed with BTAIs. Mean age was 37.6 years, with a median injury severity score (ISS) of 29. Overall mortality was 11.9%. TADI scores ranged from 3.6 to 158.6. Compared to patients with a TADI<28, patients with TADI>28 had similar median ISS scores (34 vs 29, p=0.16), and rates of both traumatic brain injury (33.3% vs 42.0%, p=0.53) and non-aortic hemorrhage control procedures (44.4% vs 33.3%, p=0.3). TADI>28 patients had a lower initial mean systolic BP (98.5 vs 121.9, p=.003), more severe hypotension (lowest systolic 77.0 vs 91.2, p=.034), lower initial GCS (6 vs 13, p=.039), higher mean admission lactate (4.6 vs 3.3, p=.036), and higher overall mortality (23.8% vs 0%, p=.048). Patients with TADI>28 received stent grafting at significantly shorter median time intervals from injury identification (median 4 hrs vs 14 hrs, p=.001). Overall causes of mortality were aortic hemorrhage related (n=3, 60%) and traumatic brain injury (n=2, 40%)., Conclusion: This simple-to-calculate index is independently correlated with mortality and urgency of stent grafting in blunt trauma patients with similar ISS. Patients with TADI scores >28 were more likely to undergo urgent stent grafting, thereby suggesting a trend in practice patterns with higher scores representing injuries that should be considered for expedited operative management. The TADI score should be validated in a larger sample of blunt trauma patients as an injury prioritization tool in the multi-system injured patient., (Copyright © 2024. Published by Elsevier Inc.)

Background/objectives: Oncolytic virotherapy is a promising approach in cancer immunotherapy. We have previously described a recombinant hybrid oncolytic virus (OV), VSV-NDV, which has a favorable safety profile and therapeutic immunogenicity, leading to direct oncolysis, abscopal effects, and prolonged survival in syngeneic in vivo tumor models. While OVs are known to mediate systemic anti-tumor immune responses, the detailed characterization of local and systemic immune responses to fusogenic oncolytic virotherapy remains unexplored., Methods and Results: We analyzed immune cell compartments in the spleen, blood, tumor-draining lymph nodes (TDLNs), and tumors over the course of VSV-NDV therapy in a bilateral syngeneic melanoma mouse model. Our results revealed significant local infiltration and activation of T lymphocytes in tumors and globally in the blood and spleen. Notably, in vivo CD8 + T cell depletion led to complete abrogation of the tumor response, highlighting the crucial role of T cells in promoting the therapeutic effects of oncolytic VSV-NDV. In vitro co-culture experiments enabled the interrogation of human immune cell responses to VSV-NDV-mediated oncolysis. Human peripheral blood mononuclear cells (PBMCs) were efficiently stimulated by exposure to VSV-NDV-infected cancer cells, which recapitulates the in vivo murine findings., Conclusions: Taken together, these data characterize a broad anti-tumor immune cell response to oncolytic VSV-NDV therapy and suggest that CD8 + T cells play a decisive role in therapeutic outcome, which supports the further development of this chimeric vector as a multimechanistic immunotherapy for solid cancers.

Since the discovery of antimicrobial agents, the misuse of antibiotics has led to the emergence of bacterial strains resistant to both antibiotics and common disinfectants like quaternary ammonium compounds (QACs). A new class, 'gemini' QACs, which contain two polar heads, has shown promise. Octenidine (OCT), a representative of this group, is effective against resistant microorganisms but has limitations such as low solubility and high cytotoxicity. In this study, we developed 16 novel OCT derivatives. These compounds were subjected to in silico screening to predict their membrane permeation. Testing against nosocomial bacterial strains (G + and G - ) and their biofilms revealed that most compounds were highly effective against G + bacteria, while compounds 7, 8, and 10-12 were effective against G - bacteria. Notably, compounds 6-8 were significantly more effective than OCT and BAC standards across the bacterial panel. Compound 12 stood out due to its low cytotoxicity and broad-spectrum antimicrobial activity, comparable to OCT. It also demonstrated impressive antifungal activity. Compound 1 was highly selective to fungi and four times more effective than OCT without its cytotoxicity. Several compounds, including 4, 6, 8, 9, 10, and 12, showed strong virucidal activity against murine cytomegalovirus and herpes simplex virus 1. In conclusion, these gemini QACs, especially compound 12, offer a promising alternative to current disinfectants, addressing emerging resistances with their enhanced antimicrobial, antifungal, and virucidal properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jan Marek reports financial support was provided by Ministry of Health of the Czech Republic. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Radiographic adjacent segment disease (ASD) ranges from 10% to 84%, depending on technique. Occurrence of symptomatic ASD is lower, with a range of 1.9% to 13%. ASD can be very debilitating and necessitate further procedures, leading to high morbidity. Herein, we explore the occurrence of adjacent segment disease when performing anterior column release in lateral interbody fusion., Methods: After institutional review board approval, 120 total patients who underwent lateral lumbar interbody fusion (LLIF) at our facility from 2013 to 2020 were retrospectively reviewed, allowing for a minimum of 3 years for follow-up time. Surgical variables and spinopelvic parameters were measured and collected by our team. Statistical measures of significance were calculated using IBM SPSS Statistics Version 29., Results: One hundred twenty total patients were included. 73.3% of patients had percutaneous screws, and 11.7% had open. Thirteen patients underwent LLIF with anterior column release (ACR). The mean lumbar lordosis (LL) was 50.1 ± 12.9, pelvic incidence (PI) was 52.8 ± 11.2, sacral slope was 33.6 ± 9.2, pelvic tilt was 18.1 ± 6.8, and sagittal vertical axis was 6.8 mm ± 30.5.Twenty four total patients had ASD after LLIF. In univariable analysis, ACR (P < 0.001) and PI-LL Mismatch (P < 0.035) were risk factors for developing ASD. In multivariable analysis, greater PI-LL mismatch was predictive of ASD (P < 0.005, OR = 1.097, and 95% confidence interval = 1.029-1.171), as was ACR (P < 0.001, OR = 9.667, and 95% confidence interval = 2.669-35.09)., Conclusions: Higher PI-LL mismatch after lumbar interbody fusion, and performance of an ACR during LLIF increased the likelihood of developing symptomatic ASD in our patients. Considering ACR to achieve the goal of correcting spinopelvic parameters should be carefully evaluated when undertaking a lateral approach., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The increasing threat of nuclear incidents and the widespread use of ionizing radiation (IR) in medical treatments underscore the urgent need for effective radiation countermeasures. Despite the availability of compounds such as amifostine, their clinical utility is significantly limited by adverse side effects and logistical challenges in administration. This study focuses on the synthesis and evaluation of novel piperazine derivatives as potential radioprotective agents, with the aim of overcoming the limitations associated with current countermeasures. We designed, synthesized, and evaluated a series of 1-(2-hydroxyethyl)piperazine derivatives. The compounds were assessed for cytotoxicity across a panel of human cell lines, and for their radioprotective effects in the MOLT-4 lymphoblastic leukemia cell line and in peripheral blood mononuclear cells (PBMCs) exposed to gamma radiation. The radioprotective efficacy was further quantified using the dicentric chromosome assay (DCA) to measure DNA damage mitigation. Among the synthesized derivatives, compound 6 demonstrated the most significant radioprotective effects in vitro , with minimal cytotoxicity across the tested cell lines. Compound 3 also showed notable efficacy, particularly in reducing dicentric chromosomes, thus indicating its potential to mitigate DNA damage from IR. Both compounds exhibited superior safety profiles and effectiveness compared to amifostine, suggesting their potential as more viable radioprotective agents. This study highlights the development of novel piperazine derivatives with promising radioprotective properties. Compound 6 emerged as the leading candidate, offering an optimal balance between efficacy and safety, with compound 3 also displaying significant potential. These findings support the further development and clinical evaluation of these compounds as safer, and more effective radiation countermeasures., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could appear to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Background: This study explored long-term outcome and functional status of patients born with critical aortic stenosis (CAS) following neonatal surgical or catheter interventions., Methods: A 40-year retrospective review of all consecutive patients within a large, single-center referral unit who required neonatal (<30 days) intervention for CAS. Additional detailed evaluation of surviving patients >7 years age was performed, with clinical assessment, objective cardiopulmonary exercise testing and state-of-the-art characterization of myocardial function (advanced echocardiography and cardiac MRI)., Results: Between 1970 and 2010, ninety-six neonates underwent CAS intervention (mean age 9 ± 7.5 days). Early death occurred in 19 (19.8%) and late death in 10 patients. Overall survival at 10 and 30 years was 70.1% and 68.5%, freedom from reintervention was 41.8% and 32.9% respectively. Among the 25 long-term survivors available for detailed assessment (median age 15.7 ± 6.4 years), 55% exhibited impaired peak oxygen uptake. Mean left ventricle (LV) ejection fraction was 65 ± 11.2%, with a mean LV end-diastolic volume z-score of 0.02 ± 1.4. Mean LV outflow tract Vmax was 2.3 ± 1.02 m/s. CAS patients had reduced LV longitudinal and increased radial strain (p = 0.003, p < 0.001 respectively). Five patients had severe LV diastolic dysfunction associated with endocardial fibroelastosis (EFE) (p = 0.0014)., Conclusion: Despite high early mortality rate, long-term survival of patients with CAS is reasonable at the expense of high reintervention rate. With successful intervention, there remained long-term clinical and subclinical LV myocardial impairment, of which EFE was one marker. Long-term follow-up of all CAS patients is crucial, involving detailed myocardial functional assessment to help elucidate physiology and optimise management., Competing Interests: Declaration of competing interest No grant support, no conflict of interest relating to this manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Intraoperative positioning system (IOPS; Centerline Biomedical, Inc) is a novel technology that allows for real-time intravascular navigation of endovascular devices using an electromagnetic field. In this report, we describe the use of IOPS for effective treatment of bilateral common iliac artery aneurysms with endovascular aortoiliac repair using iliac branch endoprostheses. Our experience suggests that this technology has the potential to reduce radiation and contrast use in endovascular procedures, although its application is currently limited. To the best of our knowledge, this is the first reported case of bilateral internal iliac cannulations for iliac branch endoprosthesis placement using IOPS., Competing Interests: None., (© 2024 The Authors.)

Hypergranulation is the abnormal accumulation of granulation tissue in a wound and is commonly seen in burns. It impairs wound healing and can predispose patients to infection. There is no gold standard treatment for hypergranulation tissue, but some options include surgical debridement, chemical cautery with silver nitrate, and topical steroids. Silver nitrate treatment is painful and can lead to scarring, so topical steroid use is on the rise. A retrospective review, between January 1, 2017 and August 30, 2021, at a tertiary burn center was performed to analyze outcomes of hypergranulation tissue after treatment with a topical 50/50 mixture of triamcinolone (Perrigo, Dublin, Ireland) and Polysporin (Johnson & Johnson, New Brunswick, NJ). One hundred and sixteen patients were treated with triamcinolone and Polysporin for hypergranulation tissue, although 24 did not meet inclusion criteria. Eighty-eight out of 92 patients were successfully treated until hypergranulation resolution, while 4/92(4.3%) required silver nitrate or surgery despite the topical cream to achieve resolution. In the 88 patients successfully treated until hypergranulation resolution, 99 areas of hypergranulation were treated. Forty-one of 99 (41.4%) hypergranulation areas resolved within 2 weeks. The average time to hypergranulation resolution was 27.5 ± 2.5 days. We found that a novel 50/50 mixture of triamcinolone and Polysporin topical ointment is an effective and safe treatment for hypergranulation tissue in burn wounds. Further prospective studies are needed to determine its efficacy and safety profile., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. 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.)

The current study imposes a new class of organophosphorus (OP)-inhibited cholinesterase reactivators by conceptualizing a family of asymmetric bisoximes with various reactivating scaffolds. Several novel nucleophilic warheads were investigated, putting forward 29 novel reactivating options, by evaluating their nucleophilicity and ability to directly decompose OP compounds. Adopting the so-called zwitterionic strategy, 17 mono-oxime and nine bisoxime reactivators were discovered with major emphasis on the bifunctional-moiety approach. Compounds were compared with clinically used standards and other known experimentally highlighted reactivators. Our results clearly favor the concept of asymmetric bisoximes as leading reactivators in terms of efficacy and versatility. These top-ranked compounds were characterized in detail by reactivation kinetics parameters and evaluated for potential CNS availability. The highlighted molecules 55, 57, and 58 with various reactivating warheads, surpassed the reactivating potency of pralidoxime and several notable uncharged reactivators. The versatility of lead drug candidate 55 was also inspected on OP-inhibited butyrylcholinesterase, revealing a much higher rate compared to existing clinical antidotes., Competing Interests: Declaration of Competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims: In patients with recently diagnosed non-ischaemic LV systolic dysfunction, left ventricular reverse remodelling (LVRR) and favourable prognosis has been documented in studies with short-term follow-up. The aim of our study was to assess the long-term clinical course and stability of LVRR in these patients., Methods and Results: We prospectively studied 133 patients (37 women; 55 [interquartile range 46, 61] years) with recently diagnosed unexplained LV systolic dysfunction, with heart failure symptoms lasting <6 months and LV ejection fraction <40% persisting after at least 1 week of therapy. All patients underwent endomyocardial biopsy (EMB) at the time of diagnosis and serial echocardiographic and clinical follow-up over 5 years. LVRR was defined as the combined presence of (1) LVEF ≥ 50% or increase in LVEF ≥ 10% points and (2) decrease in LV end-diastolic diameter index (LVEDDi) ≥ 10% or (3) LVEDDi ≤ 33 mm/m 2 . LVRR was observed in 46% patients at 1 year, in 60% at 2 years and 50% at 5 years. Additionally, 2% of patients underwent heart transplantation and 12% experienced heart failure hospitalization. During 5-year follow-up, 23 (17%) of the study cohort died. In multivariate analysis, independent predictors of mortality were baseline right atrial size (OR 1.097, CI 1.007-1.196), logBNP level (OR 2.02, CI 1.14-3.56), and PR interval (OR 1.02, CI 1.006-1.035) (P < 0.05 for all). The number of macrophages on EMB was associated with overall survival in univariate analysis only. LVRR at 1 year of follow-up was associated with a lower rate of mortality and heart failure hospitalization (P = 0.025). In multivariate analysis, independent predictors of LVRR were left ventricular end-diastolic volume index (OR 0.97, CI 0.946-0.988), LVEF (OR 0.89, CI 0.83-0.96), and diastolic blood pressure (OR 1.04, CI 1.01-1.08) (P < 0.05 for all)., Conclusions: LVRR occurs in over half of patients with recent onset unexplained LV systolic dysfunction during first 2 years of optimally guided heart failure therapy and then remains relatively stable during 5-year follow-up. Normalization of adverse LV remodelling corresponds to a low rate of mortality and heart failure hospitalizations during long-term follow-up., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)