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1.
Article in English | MEDLINE | ID: mdl-39018456

ABSTRACT

ABSTRACT: Despite the implementation of numerous strategies to prevent unintentional burns, fire-related thermal injuries remain a significant source of morbidity and mortality. Unfortunately, fires that occur in the setting of medical oxygen do so despite many safeguards and warnings that accompany oxygen therapy. Oxygen-related accidental fires can occur both within the home and medical settings, and burns associated with these events tend to produce injuries of the face and upper airways. Thermal burns of the face and upper airway are of particular concern because of the vital respiratory function of these anatomic structures, and may initially appear minor, but due to the inhalational injury mechanism, can contribute to death. In this report, three deaths associated with accidental oxygen therapy-related facial/upper airway burns are reported, one occurring during surgery, and two occurring during home-oxygen use.

2.
Nature ; 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39020163

ABSTRACT

Logged and disturbed forests are often viewed as degraded and depauperate environments compared with primary forest. However, they are dynamic ecosystems1 that provide refugia for large amounts of biodiversity2,3, so we cannot afford to underestimate their conservation value4. Here we present empirically defined thresholds for categorizing the conservation value of logged forests, using one of the most comprehensive assessments of taxon responses to habitat degradation in any tropical forest environment. We analysed the impact of logging intensity on the individual occurrence patterns of 1,681 taxa belonging to 86 taxonomic orders and 126 functional groups in Sabah, Malaysia. Our results demonstrate the existence of two conservation-relevant thresholds. First, lightly logged forests (<29% biomass removal) retain high conservation value and a largely intact functional composition, and are therefore likely to recover their pre-logging values if allowed to undergo natural regeneration. Second, the most extreme impacts occur in heavily degraded forests with more than two-thirds (>68%) of their biomass removed, and these are likely to require more expensive measures to recover their biodiversity value. Overall, our data confirm that primary forests are irreplaceable5, but they also reinforce the message that logged forests retain considerable conservation value that should not be overlooked.

3.
Cell Rep Med ; 5(7): 101642, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38981485

ABSTRACT

In order to assess homeostatic mechanisms in the lung after COVID-19, changes in the protein signature of bronchoalveolar lavage from 45 patients with mild to moderate disease at three phases (acute, recovery, and convalescent) are evaluated over a year. During the acute phase, inflamed and uninflamed phenotypes are characterized by the expression of tissue repair and host defense response molecules. With recovery, inflammatory and fibrogenic mediators decline and clinical symptoms abate. However, at 9 months, quantified radiographic abnormalities resolve in the majority of patients, and yet compared to healthy persons, all showed ongoing activation of cellular repair processes and depression of the renin-kallikrein-kinin, coagulation, and complement systems. This dissociation of prolonged reparative processes from symptom and radiographic resolution suggests that occult ongoing disruption of the lung proteome is underrecognized and may be relevant to recovery from other serious viral pneumonias.


Subject(s)
COVID-19 , Lung , Proteome , SARS-CoV-2 , Humans , COVID-19/metabolism , COVID-19/pathology , COVID-19/virology , Proteome/metabolism , Lung/metabolism , Lung/pathology , Lung/diagnostic imaging , Female , Male , Middle Aged , SARS-CoV-2/isolation & purification , Longitudinal Studies , Adult , Bronchoalveolar Lavage Fluid/chemistry , Aged
4.
Crit Care ; 28(1): 242, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39010134

ABSTRACT

BACKGROUND: Half of pediatric in-hospital cardiopulmonary resuscitation (CPR) events have an initial rhythm of non-pulseless bradycardia with poor perfusion. Our study objectives were to leverage granular data from the ICU-RESUScitation (ICU-RESUS) trial to: (1) determine the association of early epinephrine administration with survival outcomes in children receiving CPR for bradycardia with poor perfusion; and (2) describe the incidence and time course of the development of pulselessness. METHODS: Prespecified secondary analysis of ICU-RESUS, a multicenter cluster randomized trial of children (< 19 years) receiving CPR in 18 intensive care units in the United States. Index events (October 2016-March 2021) lasting ≥ 2 min with a documented initial rhythm of bradycardia with poor perfusion were included. Associations between early epinephrine (first 2 min of CPR) and outcomes were evaluated with Poisson multivariable regression controlling for a priori pre-arrest characteristics. Among patients with arterial lines, intra-arrest blood pressure waveforms were reviewed to determine presence of a pulse during CPR interruptions. The temporal nature of progression to pulselessness was described and outcomes were compared between patients according to subsequent pulselessness status. RESULTS: Of 452 eligible subjects, 322 (71%) received early epinephrine. The early epinephrine group had higher pre-arrest severity of illness and vasoactive-inotrope scores. Early epinephrine was not associated with survival to discharge (aRR 0.97, 95%CI 0.82, 1.14) or survival with favorable neurologic outcome (aRR 0.99, 95%CI 0.82, 1.18). Among 186 patients with invasive blood pressure waveforms, 118 (63%) had at least 1 period of pulselessness during the first 10 min of CPR; 86 (46%) by 2 min and 100 (54%) by 3 min. Sustained return of spontaneous circulation was highest after bradycardia with poor perfusion (84%) compared to bradycardia with poor perfusion progressing to pulselessness (43%) and bradycardia with poor perfusion progressing to pulselessness followed by return to bradycardia with poor perfusion (62%) (p < 0.001). CONCLUSIONS: In this cohort of pediatric CPR events with an initial rhythm of bradycardia with poor perfusion, we failed to identify an association between early bolus epinephrine and outcomes when controlling for illness severity. Most children receiving CPR for bradycardia with poor perfusion developed subsequent pulselessness, 46% within 2 min of CPR onset.


Subject(s)
Bradycardia , Cardiopulmonary Resuscitation , Epinephrine , Humans , Epinephrine/administration & dosage , Epinephrine/therapeutic use , Cardiopulmonary Resuscitation/methods , Cardiopulmonary Resuscitation/statistics & numerical data , Male , Female , Bradycardia/drug therapy , Bradycardia/therapy , Child, Preschool , Child , Infant , Adolescent , Intensive Care Units/statistics & numerical data , Intensive Care Units/organization & administration
5.
Ann Plast Surg ; 93(2): 163-171, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39023407

ABSTRACT

ABSTRACT: Breast ptosis presents challenges for implant-based reconstruction due to the large skin envelope. Skin-reducing mastectomy reduces the envelope but must consider many other factors including complications. Limited data exist on incision impact on outcomes. We compare oblique-elliptical and Wise-pattern incisions on complications and patient-reported quality of life in immediate implant-based reconstruction.A retrospective review of patients who underwent immediate implant-based skin-reducing mastectomy at a single institution from 2015 to 2021 was done and was divided into two cohorts: wise and oblique incisions. Demographics, complications, and patient-reported outcomes (BREAST-Q) were compared. Descriptive, t test, and chi-square test analyses, followed by adjusted linear and logistic regression models, were performed to compare complication rates and BREAST-Q scores.Eighty-nine patient breasts were analyzed, 39 (43.8%) in the oblique (OI) and 50 (56.2%) in the wise (WI) cohort. No differences in demographics or preoperative comorbidities between groups were found. The oblique incision patients had significantly more mean total complications (OI 1.46 vs WI 0.88; P = 0.048), as well as increased incidence of explantation (OI 15 vs WI 3; P = 0.003) and cellulitis (OI 14 vs WI 3; P = 0.020) compared to wise group. Linear regression analysis revealed that incision choice was a significant predictor of complication rate (ß = -1.06, 95% CI [-1.63--0.50], P = <0.001). Logistic regression analysis showed that incision was a significant predictor of specific complications such as explantation (odds ratio = 0.10, 95% CI [0.02-0.52], P = 0.006) and cellulitis (odds ratio = 0.16, 95% CI [0.03-0.73], P = 0.018), with decreased risk of choosing wise incision. There was no difference in BREAST-Q results.Ptotic patients with oblique incision are associated with higher rates of postoperative complications compared to wise incisions.These findings suggest that incision choice is an important factor in postoperative complication development and emphasizes the need for further investigation and discussion with patients during preoperative planning.


Subject(s)
Breast Implantation , Postoperative Complications , Humans , Female , Retrospective Studies , Middle Aged , Breast Implantation/methods , Adult , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Patient Reported Outcome Measures , Breast Neoplasms/surgery , Mastectomy/methods , Quality of Life , Breast Implants
6.
J Clin Oncol ; : JCO2400020, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38954782

ABSTRACT

PURPOSE: Ewing Sarcoma (ES), a rare cancer with a pathognomonic translocation resulting in the Ewing sarcoma gene (EWS)::FLI1 oncoprotein, has a poor prognosis in the relapsed/refractory (R/R) setting. Tokalas (TK)216 was designed to bind EWS::FLI1 proteins directly, disrupt protein-protein interactions, and inhibit transcription factor function. TK216 plus vincristine showed synergistic activity in preclinical tumor models. To our knowledge, we report the results of a first-in-class, first-in-human phase I/II trial of TK216 in R/R ES. PATIENTS AND METHODS: TK216 was administered intravenously as a continuous infusion to patients with R/R ES in 11 cohorts. The dosing duration of 7 days was later extended to 10, 14, and 28 days. Vincristine could be added on day 1 after cycle 2, per investigators' choice. The trial used a 3 + 3 design with an expansion cohort at the recommended phase II dose (RP2D). RESULTS: A total of 85 patients with a median age of 27 years (range, 11-77) were enrolled. The maximum tolerated dose for the 14-day infusion of TK216, 200 mg/m2 once daily, was determined in cohort 9 and selected as the RP2D. The median previous number of systemic therapies regimens was three (range, 1-10). The most frequent-related adverse events in patients treated at the RP2D included neutropenia (44.7%), anemia (29.4%), leukopenia (29.4%), febrile neutropenia (15.3%), thrombocytopenia (11.8%), and infections (17.6%). In cohorts 9 and 10, two patients had a complete response, one had a partial response, and 14 had stable disease; the 6-month progression-free survival was 11.9%. There were no responses among the eight patients in cohort 11. CONCLUSION: TK216 administered as 14-day continuous infusion with or without vincristine was well tolerated and showed limited activity at the RP2D in R/R ES.

7.
Article in English | MEDLINE | ID: mdl-38963610

ABSTRACT

Sudden death in infants remains a common and poorly understood cause of childhood mortality in the USA. Pediatric cardiac tumors, although rare, may underlie some cases of unexplained sudden infant death. Autopsy is a crucial diagnostic step in these cases, as both gross and microscopic examination of the heart may uncover occult cardiac tumors. Rhabdomyomas are the most common cardiac tumors in childhood and may result in arrythmia and sudden death. We present a case of sudden death in a healthy 5-month-old infant which initially appeared "SIDS-like" until thorough histological analysis revealed an underlying cardiac rhabdomyoma. The case is of particular importance in that the gross examination of the heart was considered completely normal, and the tumor only involved certain portions of the heart microscopically. Had a single random section of myocardium been the only heart section examined microscopically, the diagnosis might have been missed. This case emphasizes the importance of thorough microscopic examination in infant cases, especially in cases where the heart appears grossly normal.

8.
Article in English | MEDLINE | ID: mdl-38950425

ABSTRACT

CONTEXT: Data to Care (D2C) involves sharing HIV surveillance data between health care facilities and health departments to improve continuity of care for people living with HIV (PLWH). The Chicago Department of Public Health (CDPH) initiated a D2C pilot program at the University of Chicago Medicine (UCM) from June 2016 to September 2019. OBJECTIVES: To describe the proportion of patients reported by UCM as not in care who were able to be matched to CDPH enhanced HIV/AIDS Reporting System (eHARS) and to report the individual-level factors associated with matching and viral suppression. DESIGN: Retrospective program evaluation. SETTING: UCM, an academic health care center that provides HIV care to adults via a Ryan White clinic on the south side of Chicago. PARTICIPANTS: Adult PLWH who had received care at UCM but did not have current documented HIV care visit(s). MAIN OUTCOME MEASURE: Proportion of matched patients; factors associated with matching and viral suppression. RESULTS: Overall, 72.4% (n = 813/1123) of patients reported by UCM were matched by CDPH to eHARS. Individuals aged 40 to 49 years (odds ratio [OR] = 1.99; 95% confidence interval [CI], 1.10-3.62), 50 to 59 years (OR = 2.47; 95% CI, 1.37-4.47), and 60 years or older (OR = 6.18; 95% CI, 3.18-12.32) were more likely to match in eHARS. People who lived outside of Chicago (OR = 0.09; 95% CI, 0.05-0.15) or with unknown zip codes (OR = 0.08; 95% CI, 0.05-0.12) were less likely to match. Men who have sex with men and persons older than 50 years were more likely to be virally suppressed. CONCLUSIONS: D2C is an evidence-based strategy for reengagement of PLWH; however, program implementation relies on successful data matching. We found that a large proportion of patients from UCM were not matched, particularly those who were younger or lived outside of Chicago. Additional research is needed to understand ways to improve data matching to facilitate reengagement in HIV care.

9.
Ann Thorac Surg ; 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38950726

ABSTRACT

BACKGROUND: With congenital heart disease patients increasingly living into adulthood, there is a growing population of adult congenital heart disease (ACHD) patients suffering from heart failure. Limited data exist evaluating heart transplant in this population. METHODS: Retrospective review was performed of ACHD patients undergoing heart transplantation 11/1990-1/2023. Kaplan-Meier, cumulative incidence accounting for competing risk of death, and subgroup analyses comparing those with biventricular (BiV) and univentricular (UniV) physiology were performed. Data are presented as median (interquartile range) or counts (%). RESULTS: 77 patients with a median age of 36 years (27, 45) were identified, including 57 (74%) BiV and 20 (26%) UniV. Preoperatively, UniV patients were more likely to have cirrhosis (9/20 [45.0%] vs 4/57 [7.0%], p<0.001) and protein losing enteropathy (4/20 [20.0%] vs 1/57 [1.8%], p=0.015). Multiorgan transplantation was performed in 23 patients (30%) and more frequently in UniV patients (10 [50%] vs. 13[23%], p=0.04). Operative mortality was 6.5%, 2/20 (10%) among UniV and 2/57 (4%) among BiV patients, p=0.276. Median clinical follow-up was 6.0 (1.4, 13.1) years. Survival tended to be lower among UniV patients compared to BiV patients, particularly within the first year (p=0.09), but was similar for survivors beyond one year. At 5 years, incidence of rejection was 28% (17%, 38%) and coronary allograft vasculopathy was 16% (7%, 24%). CONCLUSIONS: Underlying liver disease and need for heart/liver transplantation were significantly higher among UniV patients. Survival tended to be lower among UniV, particularly within the first year, but was similar for survivors beyond one year.

10.
Nat Struct Mol Biol ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38951623

ABSTRACT

The development of precise RNA-editing tools is essential for the advancement of RNA therapeutics. CRISPR (clustered regularly interspaced short palindromic repeats) PspCas13b is a programmable RNA nuclease predicted to offer superior specificity because of its 30-nucleotide spacer sequence. However, its design principles and its on-target, off-target and collateral activities remain poorly characterized. Here, we present single-base tiled screening and computational analyses that identify key design principles for potent and highly selective RNA recognition and cleavage in human cells. We show that the de novo design of spacers containing guanosine bases at precise positions can greatly enhance the catalytic activity of inefficient CRISPR RNAs (crRNAs). These validated design principles (integrated into an online tool, https://cas13target.azurewebsites.net/ ) can predict highly effective crRNAs with ~90% accuracy. Furthermore, the comprehensive spacer-target mutagenesis revealed that PspCas13b can tolerate only up to four mismatches and requires ~26-nucleotide base pairing with the target to activate its nuclease domains, highlighting its superior specificity compared to other RNA or DNA interference tools. On the basis of this targeting resolution, we predict an extremely low probability of PspCas13b having off-target effects on other cellular transcripts. Proteomic analysis validated this prediction and showed that, unlike other Cas13 orthologs, PspCas13b exhibits potent on-target activity and lacks collateral effects.

11.
Article in English | MEDLINE | ID: mdl-38988034

ABSTRACT

BACKGROUND: Azithromycin (AZ) is a widely used antibiotic. The aim of this study was to characterise the clinical features, outcomes, and HLA association in patients with drug-induced liver injury (DILI) due to AZ. METHODS: The clinical characteristics of individuals with definite, highly likely, or probable AZ-DILI enrolled in the US Drug-Induced Liver Injury Network (DILIN) were reviewed. HLA typing was performed using an Illumina MiSeq platform. The allele frequency (AF) of AZ-DILI cases was compared to population controls, other DILI cases, and other antibiotic-associated DILI cases. RESULTS: Thirty cases (4 definite, 14 highly likely, 12 probable) of AZ-DILI were enrolled between 2004 and 2022 with a median age of 46 years, 83% white, and 60% female. Median duration of AZ treatment was 5 days. Latency was 18.5 days. 73% were jaundiced at presentation. The injury pattern was hepatocellular in 60%, cholestatic in 27%, and mixed in 3%. Ten cases (33%) were severe or fatal; 90% of these were hepatocellular. Two patients required liver transplantation. One patient with chronic liver disease died of hepatic failure. Chronic liver injury developed in 17%, of which 80% had hepatocellular injury at onset. HLA-DQA1*03:01 was significantly more common in AZ-DILI versus population controls and amoxicillin-clavulanate DILI cases (AF: 0.29 vs. 0.11, p = 0.001 and 0.002, respectively). CONCLUSION: Azithromycin therapy can lead to rapid onset of severe hepatic morbidity and mortality in adult and paediatric populations. Hepatocellular injury and younger age were associated with worse outcomes. HLA-DQA1*03:01 was significantly more common in AZ cases compared to controls.

13.
Childs Nerv Syst ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992185

ABSTRACT

PURPOSE: The spheno-occipital synchondrosis (SOS) is an important site of endochondral ossification in the cranial base that closes prematurely in Apert, Crouzon, and Pfeiffer syndromes, which contributes to varying degrees of midface hypoplasia. The facial dysmorphology of Muenke syndrome, in contrast, is less severe with low rates of midface hypoplasia. We thus evaluated the timing of SOS fusion and cephalometric landmarks in patients with Muenke syndrome compared to normal controls. METHODS: Patients with Muenke syndrome who had at least one fine-cut head computed tomography scan performed from 2000 to 2020 were retrospectively reviewed. A case-control study was performed of patient scans and age- and sex-matched control scans. SOS fusion status was evaluated as open, partially closed, or closed. RESULTS: We included 28 patients and compared 77 patient scans with 77 control scans. Kaplan-Meier analysis demonstrated an insignificantly earlier timeline of SOS fusion in Muenke syndrome (p = 0.300). Mean sella-orbitale (SO) distance was shorter (44.0 ± 6.6 vs. 47.7 ± 6.7 mm, p < 0.001) and mean sella-nasion-Frankfort horizontal (SN-FH) angle was greater (12.1° ± 3.8° vs. 10.1° ± 3.2°, p < 0.001) in the Muenke group, whereas mean sella-nasion-A point (SNA) angle was similar and normal (81.1° ± 5.7° vs. 81.4° ± 4.7°, p = 0.762). CONCLUSION: Muenke syndrome is characterized by mild and often absent midfacial hypoplasia, with the exception of slight retropositioning of the infraorbital rim. Interestingly, SOS fusion patterns in these patients are not significantly different from age- and sex-matched controls despite an increased odds of fusion. It is possible that differences in timing of SOS fusion may manifest phenotypically at the infraorbital rim rather than at the maxilla.

15.
Nat Commun ; 15(1): 5809, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38987584

ABSTRACT

Human papillomaviruses (HPVs) cause most cervical cancers and an increasing number of anogenital and oral carcinomas, with most cases caused by HPV16 or HPV18. HPV hijacks host signalling pathways to promote carcinogenesis. Understanding these interactions could permit identification of much-needed therapeutics for HPV-driven malignancies. The Hippo signalling pathway is important in HPV+ cancers, with the downstream effector YAP playing a pro-oncogenic role. In contrast, the significance of its paralogue TAZ remains largely uncharacterised in these cancers. We demonstrate that TAZ is dysregulated in a HPV-type dependent manner by a distinct mechanism to that of YAP and controls proliferation via alternative cellular targets. Analysis of cervical cancer cell lines and patient biopsies revealed that TAZ expression was only significantly increased in HPV18+ and HPV18-like cells and TAZ knockdown reduced proliferation, migration and invasion only in HPV18+ cells. RNA-sequencing of HPV18+ cervical cells revealed that YAP and TAZ have distinct targets, suggesting they promote carcinogenesis by different mechanisms. Thus, in HPV18+ cancers, YAP and TAZ play non-redundant roles. This analysis identified TOGARAM2 as a previously uncharacterised TAZ target and demonstrates its role as a key effector of TAZ-mediated proliferation, migration and invasion in HPV18+ cancers.


Subject(s)
Adaptor Proteins, Signal Transducing , Cell Proliferation , Hippo Signaling Pathway , Human papillomavirus 18 , Papillomavirus Infections , Protein Serine-Threonine Kinases , Signal Transduction , Transcription Factors , Uterine Cervical Neoplasms , YAP-Signaling Proteins , Humans , Female , Uterine Cervical Neoplasms/virology , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathology , Transcription Factors/metabolism , Transcription Factors/genetics , Cell Line, Tumor , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , YAP-Signaling Proteins/metabolism , Papillomavirus Infections/virology , Papillomavirus Infections/metabolism , Papillomavirus Infections/genetics , Papillomavirus Infections/pathology , Human papillomavirus 18/genetics , Human papillomavirus 18/metabolism , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Transcriptional Coactivator with PDZ-Binding Motif Proteins/metabolism , Cell Movement , Gene Expression Regulation, Neoplastic , Human papillomavirus 16/genetics , Human papillomavirus 16/metabolism , Trans-Activators/metabolism , Trans-Activators/genetics , Carcinogenesis/genetics
16.
Water Res ; 261: 122028, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38991248

ABSTRACT

Emerging evidence indicates that micro- and macro-plastics present in water can support a diverse microbial community, including potential human pathogens (e.g., bacteria, viruses). This interaction raises important concerns surrounding the role and suitability of current bathing water regulations and associated pathogen exposure risk within beach environments. In response to this, we critically evaluated the available evidence on plastic-pathogen interactions and identified major gaps in knowledge. This review highlighted the need for a conceptual shift in risk management at public beaches recognising: (i) interconnected environmental risks, e.g., associations between microbial compliance parameters, potential pathogens and both contemporary and legacy plastic pollution; and (ii) an appreciation of risk of exposure to plastic co-pollutants for both water and waterside users. We present a decision-making framework to identify options to manage plastic-associated pathogen risks alongside short- and longer-term research priorities. This advance will help deliver improvements in managing plastic-associated pathogen risk, acknowledging that human exposure potential is not limited to only those who engage in water-based activity. We argue that adopting these recommendations will help create an integrated approach to managing and reducing human exposure to pathogens at bathing, recreational water and beach environments.

18.
Chem Sci ; 15(27): 10359-10365, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38994411

ABSTRACT

Carbon-carbon (C-C) bond formation is a cornerstone of synthetic chemistry, relying on routes such as transition-metal mediated cross-coupling for the introduction of new carbon-based functionality. For {[M] n+-C} (M = metal) structural units, studies that offer well-defined relationships between metal oxidation state, hydrocarbon strain, and {[M] n+-C} bond thermochemistry are thus informative, providing a means to reliably access new product classes. Here, we show that one-electron oxidation of the iron tucked-in complex [(η6-C5Me4[double bond, length as m-dash]CH2)Fe(dnppe)] (dnppe = 1,2-bis(di-n-propylphosphino)ethane) results in C(sp3)-C(sp3) bond formation giving unique {Fe2} dimers. Freeze-quenched CW X-band EPR spectroscopy allowed for spectroscopic identification of the reactive [(η6-C5Me4[double bond, length as m-dash]CH2)Fe(dnppe)]+ intermediate. Density functional theory (DFT) calculations reveal a primarily Fe-centered radical and a weak {[Fe]-C} bond (BDE[Fe]-C = 24.5 kcal mol-1, c.f. BDEC-C(ethane) = 90 kcal mol-1). For comparison, a structurally analogous Fe(iii) methyl complex was prepared, [Cp*Fe(dnppe)(CH3)]+ (Cp* = C5Me5 -), where C(sp3)-C(sp3) coupling was not observed, consistent with a larger calculated BDE[Fe]-C value of 47.8 kcal mol-1. These data are analogized to the simple hydrocarbons ethane and cyclopropane, where a strain-induced BDEC-C decrease of 33 kcal mol-1 is witnessed on cyclization.

19.
Blood ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39008818

ABSTRACT

Chronic graft-vs.-host disease (GVHD) is associated with morbidity, mortality, impaired quality of life, prolonged immunosuppressive (IS) therapy, and infection risk after allogeneic hematopoietic cell transplantation (HCT). Major strides have occurred in the understanding of chronic GVHD biology, NIH Consensus meetings have refined rigorous approaches to diagnosis, staging and response criteria, major interventional trials have established standard benchmarks for treatment outcome, and three agents to date have been FDA-approved for treating steroid-refractory chronic GVHD. Promising results from several recent trials have led some but not others to conclude that the risk of developing chronic GVHD is sufficiently low to by-and-large be considered a major post-HCT complication of the past. We propose that it is time to critically examine the results of contemporary GVHD prophylaxis regimens and discuss the state-of-the-science and associated controversies in spectrum of conclusions reached as to the risk of chronic GVHD. With these data, the current chronic GVHD incidence can be most precisely determined, and the present and future burden of chronic GVHD-affected patients be accurately modeled. Through review of existing evidence, we highlight unresolved needs and opportunities to refine best GVHD prophylaxis or preemptive therapy approaches, optimize established chronic GVHD therapy, and make the argument that support of preclinical and clinical research is critical in improving patient outcomes.

20.
Article in English | MEDLINE | ID: mdl-39009181

ABSTRACT

BACKGROUND: Physician involvement in political advocacy has become increasingly important in recent years. This study aims to explore the types of involvement and barriers to involvement in political advocacy among American Shoulder and Elbow Surgeons (ASES) members, identify issues considered most important by ASES members, and assess demographic factors that might correlate with involvement in political advocacy efforts among ASES members. METHODS: This survey was conducted by the ASES Political Advocacy Committee over a two-week period in June 2021. The survey collected demographic information including sex, ethnicity, years in practice, practice type, political affiliation, and level of current involvement in political advocacy. Additional questions consisted of thoughts regarding current health care policy issues and the role of the American Academy of Orthopaedic Surgeons (AAOS)/ASES regarding such policy issues. RESULTS: We received 297 responses for a total response rate of 27%. Of those who responded, 24.6% identified as Democrat, 33% identified as Republican, and 42.4% identified as Independent. There was no difference in political affiliation between membership groups. Physician Reimbursement (82%), Medical Liability Reform (50%), and Physician Ownership (50%) were the most important issues identified among respondents. Physician Ownership, Physician Reimbursement and GME and Student Loan Reform were most important to those in early practice, while Quality and Research was most important to those with greater than 25 years of practice experience. CONCLUSION: There is strong agreement among surgeons regarding the most important political advocacy issues. The efforts of the AAOS and ASES should focus on these areas. Additionally, the vast majority of respondents felt that advocacy efforts had a positive impact on patients and surgeons.

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