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1.
Sci Rep ; 14(1): 10790, 2024 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-38734737

RESUMEN

In this two-center prospective cohort study of children on ECMO, we assessed a panel of plasma brain injury biomarkers using exploratory factor analysis (EFA) to evaluate their interplay and association with outcomes. Biomarker concentrations were measured daily for the first 3 days of ECMO support in 95 participants. Unfavorable composite outcome was defined as in-hospital mortality or discharge Pediatric Cerebral Performance Category > 2 with decline ≥ 1 point from baseline. EFA grouped 11 biomarkers into three factors. Factor 1 comprised markers of cellular brain injury (NSE, BDNF, GFAP, S100ß, MCP1, VILIP-1, neurogranin); Factor 2 comprised markers related to vascular processes (vWF, PDGFRß, NPTX1); and Factor 3 comprised the BDNF/MMP-9 cellular pathway. Multivariable logistic models demonstrated that higher Factor 1 and 2 scores were associated with higher odds of unfavorable outcome (adjusted OR 2.88 [1.61, 5.66] and 1.89 [1.12, 3.43], respectively). Conversely, higher Factor 3 scores were associated with lower odds of unfavorable outcome (adjusted OR 0.54 [0.31, 0.88]), which is biologically plausible given the role of BDNF in neuroplasticity. Application of EFA on plasma brain injury biomarkers in children on ECMO yielded grouping of biomarkers into three factors that were significantly associated with unfavorable outcome, suggesting future potential as prognostic instruments.


Asunto(s)
Biomarcadores , Lesiones Encefálicas , Oxigenación por Membrana Extracorpórea , Humanos , Biomarcadores/sangre , Masculino , Femenino , Recién Nacido , Lactante , Lesiones Encefálicas/sangre , Lesiones Encefálicas/terapia , Lesiones Encefálicas/diagnóstico , Lesiones Encefálicas/metabolismo , Niño , Preescolar , Estudios Prospectivos , Análisis Factorial , Mortalidad Hospitalaria , Resultado del Tratamiento
2.
Sci Rep ; 14(1): 11599, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773296

RESUMEN

Fibromyalgia syndrome (FMS) is a chronic pain syndrome characterized by disruptions in pain processing within the central nervous system. It exhibits a high prevalence among patients with a history of traumatic experiences, notably childhood sexual abuse (CSA). This study compared the efficacy of hyperbaric oxygen therapy (HBOT) to the current pharmacological standard of care for individuals suffering from CSA-related FMS. Forty-eight participants diagnosed with FMS and a history of CSA were randomly assigned to either the HBOT group (60 sessions of 100% oxygen at 2 ATA for 90 min, with air breaks every 5 min) or the medication (MED) group (FDA-approved medications, Pregabalin and Duloxetine). The primary endpoint was the Fibromyalgia impact questionnaire (FIQ) score, while secondary endpoints encompassed emotional status and daily functioning questionnaires, as well as pain thresholds and conditioned pain modulation tests. Brain activity was evaluated through single photon emission computed tomography (SPECT). Results revealed a significant group-by-time interaction for the FIQ score favoring HBOT over MED (p < 0.001), with a large effect size (Cohen's d = - 1.27). Similar findings were observed in emotional symptoms and functional measures. SPECT imaging demonstrated an increase in activity in pre-frontal and temporal brain areas, which correlated with symptoms improvement. In conclusion, HBOT exhibited superior benefits over medications in terms of physical, functional, and emotional improvements among FMS patients with a history of CSA. This associated with increased activity in pre-frontal and temporal brain areas, highlighting the neuroplasticity effect of HBOT.


Asunto(s)
Abuso Sexual Infantil , Fibromialgia , Oxigenoterapia Hiperbárica , Humanos , Fibromialgia/terapia , Oxigenoterapia Hiperbárica/métodos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Abuso Sexual Infantil/psicología , Estudios Prospectivos , Clorhidrato de Duloxetina/uso terapéutico , Pregabalina/uso terapéutico , Resultado del Tratamiento , Encuestas y Cuestionarios , Tomografía Computarizada de Emisión de Fotón Único , Analgésicos/uso terapéutico
3.
Org Lett ; 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38753853

RESUMEN

1,5-Polyol structures present challenges in stereocontrol, configurational assignment, and diastereomer separation; these are all compromised by remote stereochemical relationships. A configuration-encoded approach with alcohol configurations previously established within enantiopure building blocks offers a versatile solution to these issues. The iterative construction begins with α-silyloxyaldehydes; here, we introduce an enantioselective and step-economical route from alkynes to α-silyloxyaldehydes via silyl cation-induced ring opening of enol ester epoxides. This development enables an efficient configuration-encoded synthesis of the C22-C41 fragment of the bastimolides.

4.
Circ Heart Fail ; 17(5): e010904, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38602105

RESUMEN

BACKGROUND: Heart transplant (HT) in recipients with left ventricular assist devices (LVADs) is associated with poor early post-HT outcomes, including primary graft dysfunction (PGD). As complicated heart explants in recipients with LVADs may produce longer ischemic times, innovations in donor heart preservation may yield improved post-HT outcomes. The SherpaPak Cardiac Transport System is an organ preservation technology that maintains donor heart temperatures between 4 °C and 8 °C, which may minimize ischemic and cold-induced graft injuries. This analysis sought to identify whether the use of SherpaPak versus traditional cold storage was associated with differential outcomes among patients with durable LVAD undergoing HT. METHODS: Global Utilization and Registry Database for Improved Heart Preservation-Heart (NCT04141605) is a multicenter registry assessing post-HT outcomes comparing 2 methods of donor heart preservation: SherpaPak versus traditional cold storage. A retrospective review of all patients with durable LVAD who underwent HT was performed. Outcomes assessed included rates of PGD, post-HT mechanical circulatory support use, and 30-day and 1-year survival. RESULTS: SherpaPak (n=149) and traditional cold storage (n=178) patients had similar baseline characteristics. SherpaPak use was associated with reduced PGD (adjusted odds ratio, 0.56 [95% CI, 0.32-0.99]; P=0.045) and severe PGD (adjusted odds ratio, 0.31 [95% CI, 0.13-0.75]; P=0.009), despite an increased total ischemic time in the SherpaPak group. Propensity matched analysis also noted a trend toward reduced intensive care unit (SherpaPak 7.5±6.4 days versus traditional cold storage 11.3±18.8 days; P=0.09) and hospital (SherpaPak 20.5±11.9 days versus traditional cold storage 28.7±37.0 days; P=0.06) lengths of stay. The 30-day and 1-year survival was similar between groups. CONCLUSIONS: SherpaPak use was associated with improved early post-HT outcomes among patients with LVAD undergoing HT. This innovation in preservation technology may be an option for HT candidates at increased risk for PGD. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04141605.


Asunto(s)
Insuficiencia Cardíaca , Trasplante de Corazón , Corazón Auxiliar , Preservación de Órganos , Sistema de Registros , Humanos , Masculino , Femenino , Persona de Mediana Edad , Preservación de Órganos/métodos , Estudios Retrospectivos , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/cirugía , Insuficiencia Cardíaca/mortalidad , Resultado del Tratamiento , Adulto , Anciano , Disfunción Primaria del Injerto , Factores de Tiempo
5.
Proc Biol Sci ; 291(2021): 20240021, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38628119

RESUMEN

Conventional life-history theory predicts that energy-demanding events such as reproduction and migration must be temporally segregated to avoid resource limitation. Here, we provide, to our knowledge, the first direct evidence of 'itinerant breeding' in a migratory bird, an incredibly rare breeding strategy (less than 0.1% of extant bird species) that involves the temporal overlap of migratory and reproductive periods of the annual cycle. Based on GPS-tracking of over 200 female American woodcock, most female woodcock (greater than 80%) nested more than once (some up to six times) with short re-nest intervals, and females moved northwards on average 800 km between first and second nests, and then smaller distances (ca 200+ km) between subsequent nesting attempts. Reliance on ephemeral habitat for breeding, ground-nesting and key aspects of life history that reduce both the costs of reproduction and migration probably explain the prevalence of this rare phenotype in woodcock and why itinerant breeding so rarely occurs in other bird species.


Asunto(s)
Charadriiformes , Rasgos de la Historia de Vida , Animales , Femenino , Estaciones del Año , Reproducción , Aves , Ecosistema , Migración Animal
7.
Resusc Plus ; 18: 100609, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38549693

RESUMEN

Aim: We sought to determine if higher plasma levels of brain injury biomarkers neurofilament light (NfL), phosphorylated tau 181 (pT181), tau, and ubiquitin C-terminal hydrolase L1 (UCHL1) were associated with unfavorable outcomes in children supported on extracorporeal membrane oxygenation (ECMO) with and without preceding cardiac arrest. Methods: We conducted a secondary analysis of a two-center prospective observational study of ECMO patients 0-<18 years. Plasma concentrations of NfL, pT181, tau, and UCHL1 were measured on ECMO days 1, 2 and 3. Unfavorable outcome was defined as in-hospital mortality or discharge Pediatric Cerebral Performance Category (PCPC) >2 with decline from baseline PCPC among survivors. Results: Among 88 children on ECMO, mean tau levels were significantly higher on each of the first three ECMO days in children who underwent extracorporeal cardiopulmonary resuscitation (ECPR) compared to those with non-ECPR cardiac arrest or with no cardiac arrest preceding ECMO. Higher ECMO day 1 tau levels were significantly associated with increased hazard of unfavorable outcome in unadjusted (HR, 1.35, 95% CI 1.09-1.66) and adjusted (HR, 1.42; 95% CI 1.13-1.79) models. Higher levels of NfL or pT181 were not associated with increased hazard for unfavorable outcome in multivariable models. UCHL1 values were outside of detectable limits and thus deferred from analysis. Conclusions: Levels of tau were significantly associated with increased hazard of death or unfavorable neurologic outcome in unadjusted and adjusted models. Biomarkers of brain injury, particularly tau, may aid in detection of neurologic injury and neuroprognostication in patients on ECMO with and without preceding cardiac arrest.

8.
Foot Ankle Spec ; : 19386400241235389, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38450616

RESUMEN

Pin tract infections are virtually universal complications with the use of external fixation. While most are superficial and respond to oral antibiotics and local care, septic loosening may occur at the bone-pin interface, which may lead to instability of the fixator, catastrophic failure, fracture, and long-term osteomyelitis. Classification systems and prevention protocols have been developed to address this ubiquitous complication. Treatment of severe pin tract infections often requires debridement, parenteral antibiotics, and removal of the offending pin or the entire external fixator. In cases of osteomyelitic pin tracks, a sizable cavity is often present. We describe a simple technique for treatment of deep bone pin tract infection through the use of debridement, irrigation, and an antibiotic "sparkler," which is a specially prepared percutaneous implant of antibiotic laden bone cement.Levels of Evidence: Level 5.

9.
Pediatr Transplant ; 28(3): e14708, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38553812

RESUMEN

BACKGROUND: The aims of the study were to assess the performance of a clinically available cell-free DNA (cfDNA) assay in a large cohort of pediatric and adult heart transplant recipients and to evaluate performance at specific cut points in detection of rejection. METHODS: Observational, non-interventional, prospective study enrolled pediatric and adult heart transplant recipients from seven centers. Biopsy-associated plasma samples were used for cfDNA measurements. Pre-determined cut points were tested for analytic performance. RESULTS: A total of 487 samples from 160 subjects were used for the analysis. There were significant differences for df-cfDNA values between rejection [0.21% (IQR 0.12-0.69)] and healthy samples [0.05% (IQR 0.01-0.14), p < .0001]. The pediatric rejection group had a median df-cfDNA value of 0.93% (IQR 0.28-2.84) compared to 0.09% (IQR 0.04-0.23) for healthy samples, p = .005. Overall negative predictive value was 0.94 while it was 0.99 for pediatric patients. Cut points of 0.13% and 0.15% were tested for various types of rejection profiles and were appropriate to rule out rejection. CONCLUSION: The study suggests that pediatric patients with rejection show higher levels of circulating df-cfDNA compared to adults and supports the specific cut points for clinical use in pediatric and adult patients with overall acceptable performance.


Asunto(s)
Ácidos Nucleicos Libres de Células , Trasplante de Corazón , Adulto , Humanos , Niño , Estudios Prospectivos , Biomarcadores , Rechazo de Injerto , Donantes de Tejidos
11.
ACS Med Chem Lett ; 15(1): 123-131, 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38229758

RESUMEN

Inhibition of glucosylceramide synthase (GCS) has been proposed as a therapeutic strategy for the treatment of Parkinson's Disease (PD), particularly in patients where glycosphingolipid accumulation and lysosomal impairment are thought to be contributing to disease progression. Herein, we report the late-stage optimization of an orally bioavailable and CNS penetrant isoindolinone class of GCS inhibitors. Starting from advanced lead 1, we describe efforts to identify an improved compound with a lower human dose projection, minimal P-glycoprotein (P-gp) efflux, and acceptable pregnane X receptor (PXR) profile through fluorine substitution. Our strategy involved the use of predicted volume ligand efficiency to advance compounds with greater potential for low human doses down our screening funnel. We also applied minimized electrostatic potentials (Vmin) calculations for hydrogen bond acceptor sites to rationalize P-gp SAR. Together, our strategies enabled the alignment of a lower human dose with reduced P-gp efflux, and favorable PXR selectivity for the discovery of compound 12.

12.
JACC Heart Fail ; 12(3): 438-447, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38276933

RESUMEN

BACKGROUND: Extended criteria donor (ECD) hearts available with donation after brain death (DBD) are underutilized for transplantation due to limitations of cold storage. OBJECTIVES: This study evaluated use of an extracorporeal perfusion system on donor heart utilization and post-transplant outcomes in ECD DBD hearts. METHODS: In this prospective, single-arm, multicenter study, adult heart transplant recipients received ECD hearts using an extracorporeal perfusion system if hearts met study criteria. The primary outcome was a composite of 30-day survival and absence of severe primary graft dysfunction (PGD). Secondary outcomes were donor heart utilization rate, 30-day survival, and incidence of severe PGD. The safety outcome was the mean number of heart graft-related serious adverse events within 30 days. Additional outcomes included survival through 2 years benchmarked to concurrent nonrandomized control subjects. RESULTS: A total of 173 ECD DBD hearts were perfused; 150 (87%) were successfully transplanted; 23 (13%) did not meet study transplantation criteria. At 30 days, 92% of patients had survived and had no severe PGD. The 30-day survival was 97%, and the incidence of severe PGD was 6.7%. The mean number of heart graft-related serious adverse events within 30 days was 0.17 (95% CI: 0.11-0.23). Patient survival was 93%, 89%, and 86% at 6, 12, and 24 months, respectively, and was comparable with concurrent nonrandomized control subjects. CONCLUSIONS: Use of an extracorporeal perfusion system resulted in successfully transplanting 87% of donor hearts with excellent patient survival to 2 years post-transplant and low rates of severe PGD. The ability to safely use ECD DBD hearts could substantially increase the number of heart transplants and expand access to patients in need. (International EXPAND Heart Pivotal Trial [EXPANDHeart]; NCT02323321; Heart EXPAND Continued Access Protocol; NCT03835754).


Asunto(s)
Insuficiencia Cardíaca , Trasplante de Corazón , Adulto , Humanos , Supervivencia de Injerto , Insuficiencia Cardíaca/cirugía , Trasplante de Corazón/métodos , Preservación de Órganos/métodos , Estudios Prospectivos , Estudios Retrospectivos , Donantes de Tejidos
13.
Rheumatol Ther ; 11(1): 113-127, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38001304

RESUMEN

INTRODUCTION: This retrospective cohort study (GSK213737) aimed to characterize treatment patterns, healthcare resource utilization (HCRU), and costs in patients with lupus nephritis (LN) initiating immunosuppressant therapy in clinical practice in Germany, to better understand the full picture of the real-world burden of LN. METHODS: Adult patients with LN who initiated mycophenolate mofetil (MMF), intravenous cyclophosphamide (CYC), azathioprine (AZA), tacrolimus, cyclosporin A, or rituximab therapy in 2011-2017 (index therapy) were identified from the Betriebskrankenkassen German Sickness Fund database. Treatment patterns, including immunosuppressant discontinuations, and therapy switches, were assessed (maximum follow-up 4 years). Corticosteroid use, HCRU, and total economic costs were also evaluated. HCRU and costs were compared with matched controls (individuals without systemic lupus erythematosus [SLE]/LN matched by age, sex, and baseline Charlson Comorbidity Index). RESULTS: Among 334 patients with LN, the median (interquartile range) duration of index immunosuppressant therapy use was 380.5 (126, 1064) days. Of those patients with 4 years complete enrollment, 70.8% had ≥ 1 discontinuation and 28.8% switched therapy. While most patients (71.2%) received only one immunosuppressant, gaps in treatment were common. After 1 year of follow-up, 41.6% of patients had a prednisone-equivalent corticosteroid dose of ≥ 7.5 mg/day. Patients with LN had greater HCRU use for most categories assessed and increased mean total costs per person-year versus controls (€15,115.99 versus €4,081.88 in the first year of follow-up). CONCLUSIONS: This real-world analysis demonstrated the considerable burden of immunosuppressant-treated LN in Germany, with a high rate of discontinuations, frequent use of high-dose corticosteroids, and substantial HCRU/costs.

14.
Oncologist ; 29(2): e237-e247, 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-37756655

RESUMEN

BACKGROUND: With the COVID-19 pandemic came rapid uptake in virtual oncology care. During this, sociodemographic inequities in access to virtual visits (VVs) have become apparent. To better understand these issues, we conducted a qualitative study to describe the perceived usability and acceptability of VVs among Black adults diagnosed with cancer. METHODS: Adults who self-identified as Black and had a diagnosis of prostate, multiple myeloma, or head and neck cancer were recruited from 2 academic medical centers, and their community affiliates to participate in a semi-structured interview, regardless of prior VV experience. A patient and family advisory board was formed to inform all components of the study. Interviews were conducted between September 2, 2021 and February 23, 2022. Transcripts were organized topically, and themes and subthemes were determined through iterative and interpretive immersion/crystallization cycles. RESULTS: Of the 49 adults interviewed, 29 (59%) had participated in at least one VV. Three overarching themes were derived: (1) VVs felt comfortable and convenient in the right contexts; (2) the technology required for VVs with video presented new challenges, which were often resolved by an audio-only telephone call; and (3) participants reported preferring in-person visits, citing concerns regarding gaps in nonverbal communication, trusting providers, and distractions during VV. CONCLUSION: While VVs were reported to be acceptable in specific circumstances, Black adults reported preferring in-person care, in part due to a perceived lack of interpersonal connectedness. Nonetheless, retaining reimbursement for audio-only options for VVs is essential to ensure equitable access for those with less technology savvy and/or limited device/internet capabilities.


Asunto(s)
COVID-19 , Pandemias , Adulto , Masculino , Humanos , Oncología Médica , Centros Médicos Académicos , COVID-19/epidemiología , Internet
15.
Cancer Rep (Hoboken) ; 7(1): e1929, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37884691

RESUMEN

BACKGROUND: The burden of oral cancer in Nigeria is increasing. Different studies have shown how public education on oral cancer have increased knowledge of oral cancer across populations, however, it is not known if these practices are adopted by oral physicians, oral and maxillofacial surgeons, and oral pathologists in Nigeria. AIMS: To investigate the patient oral cancer education strategies adopted by oral physicians, oral and maxillofacial surgeons, and oral pathologists in Nigeria. METHODS: This study adopted an analytical cross-sectional study design. This study surveyed practicing oral physicians, oral and maxillofacial surgeons, and oral pathologists in Nigeria. An e-questionnaire was used for this study. The data were analyzed using the SPSS Version 20 software, and a p-value of <.05 was used to determine the level of statistical significance. RESULTS: The study's response rate was 46.6% (75/161). The 75 participants were from the six geopolitical zones in Nigeria responded to the survey questionnaire. Even though more than half (43/75, 57.3%) of the respondents have never received any training since their post-bachelor's degree qualification on the strategies that can be used in educating patients on oral cancer, majority (54/75, 72.0%) of them knew at least one education strategy; also, the most known (36/54, 66.7%) and utilized (33/54, 61.3%) strategy among those respondents who were aware of patient education strategy was health talk. Only 38.7% (29/75) of the respondents reported that health learning materials (posters, leaflets, fliers, and flipcharts) are available in their clinics, all of which were in insufficient quantities. Also, 93.3% (70/75) of the respondents opined that it is worthwhile that dental clinics/hospitals in Nigeria invest in the provision of oral cancer learning materials for patient use. Inferential statistical analysis did not reveal any significant relationship between the respondents' characteristics and their awareness and practice on patient oral cancer education strategies. CONCLUSION: This study identified that many oral physicians, oral and maxillofacial surgeons, and oral pathologists in Nigeria lack the needed capacity to educate their patients on oral cancer. There is a need to strengthen their capacity by giving them training on patient oral cancer education strategies, and by providing them with good quality and enough teaching aids.


Asunto(s)
Neoplasias de la Boca , Médicos , Humanos , Cirujanos Oromaxilofaciales , Estudios Transversales , Patólogos , Educación del Paciente como Asunto
16.
JACC Heart Fail ; 12(3): 427-437, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38032571

RESUMEN

Historically, heart transplantation (HT) has relied on the use of traditional cold storage for donor heart preservation. This organ preservation modality has several limitations, including the risk for ischemic and cold-induced graft injuries that may contribute to primary graft dysfunction and poor post-HT outcomes. In recent years, several novel donor heart preservation modalities have entered clinical practice, including the SherpaPak Cardiac Transport System of controlled hypothermic preservation, and the Transmedics Organ Care System of ex vivo perfusion. Such technologies are altering the landscape of HT by expanding the geographic reach of procurement teams and enabling both donation after cardiac death and the use of expanded criteria donor hearts. This paper will review the emerging evidence on the association of these modalities with improved post-HT outcomes, and will also suggest best practices for selecting between donor heart preservation techniques.


Asunto(s)
Insuficiencia Cardíaca , Trasplante de Corazón , Humanos , Trasplante de Corazón/métodos , Donantes de Tejidos , Corazón , Preservación de Órganos/métodos
17.
Artículo en Inglés | MEDLINE | ID: mdl-38065238

RESUMEN

BACKGROUND: Cardiac metabolism is altered in heart failure and ischemia-reperfusion injury states. We hypothesized that metabolomic profiling during ex situ normothermic perfusion before heart transplantation (HT) would lend insight into myocardial substrate utilization and report on subclinical and clinical allograft dysfunction risk. METHODS: Metabolomic profiling was performed on serial samples of ex situ normothermic perfusate assaying biomarkers of myocardial injury in lactate and cardiac troponin I (TnI) as well as metabolites (66 acylcarnitines, 15 amino acids, nonesterified fatty acids [NEFA], ketones, and 3-hydroxybutyrate). We tested for change over time in injury biomarkers and metabolites, along with differential changes by recovery strategy (donation after circulatory death [DCD] vs donation after brain death [DBD]). We examined associations between metabolites, injury biomarkers, and primary graft dysfunction (PGD). Analyses were performed using linear mixed models adjusted for recovery strategy, assay batch, donor-predicted heart mass, and time. RESULTS: A total of 176 samples from 92 ex situ perfusion runs were taken from donors with a mean age of 35 (standard deviation 11.3) years and a median total ex situ perfusion time of 234 (interquartile range 84) minutes. Lactate trends over time differed significantly by recovery strategy, while TnI increased during ex situ perfusion regardless of DCD vs DBD status. We found fuel substrates were rapidly depleted during ex situ perfusion, most notably the branched-chain amino acids leucine/isoleucine, as well as ketones, 3-hydroxybutyrate, and NEFA (least squares [LS] mean difference from the first to last time point -1.7 to -4.5, false discovery rate q < 0.001). Several long-chain acylcarnitines (LCAC), including C16, C18, C18:1, C18:2, C18:3, C20:3, and C20:4, increased during the perfusion run (LS mean difference 0.42-0.67, q < 0.001). Many LCACs were strongly associated with lactate and TnI. The change over time of many LCACs was significantly different for DCD vs DBD, suggesting differential trends in fuel substrate utilization by ischemic injury pattern. Changes in leucine/isoleucine, arginine, C12:1-OH/C10:1-DC, and C16-OH/C14-DC were associated with increased odds of moderate-severe PGD. Neither end-of-run nor change in lactate or TnI was associated with PGD. CONCLUSIONS: Metabolomic profiling of ex situ normothermic perfusion solution reveals a pattern of fuel substrate utilization that correlates with subclinical and clinical allograft dysfunction. This study highlights a potential role for interventions focused on fuel substrate modification in allograft conditioning during ex situ perfusion to improve allograft outcomes.

18.
JTCVS Tech ; 22: 228-236, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38152175

RESUMEN

Objective: We developed a hybrid technique for repairing post-myocardial infarction (MI) ventricular septal defect (VSD) that combines infarct exclusion with patch and a nitinol-mesh septal occluder device (SOD) to provide a scaffold to support the damaged septal wall. Here, we compare outcomes of patients with post-MI VSD repaired using patch only or hybrid patch/SOD. Methods: Patients undergoing post-MI VSD repair at our institution from 2013 to 2022 who received patch alone or patch/SOD repair were analyzed. Primary outcome was survival to hospital discharge. Clinical outcomes and echocardiograms were also analyzed. Results: Over a 9-year period, 24 patients had post-MI VSD repair at our institution with either hybrid patch/SOD (n = 10) or patch only repair (n = 14). VSD size was 18 ± 5.8 mm for patch/SOD and 17 ± 4.6 mm for patch only. In the patch/SOD repair cohort, average size of SOD implant was 23.6 ± 5.6 mm. Mild left ventricular dysfunction was present prerepair and was unchanged postrepair in both groups; however, moderate-to-severe right ventricular (RV) dysfunction was common in both groups before repair. RV function worsened or persisted as severe in 10% of hybrid versus 54% of patch-only patients postrepair. Tricuspid annular systolic excursion and RV:left ventricle diameter ratio, quantitative metrics of RV function, improved after patch/SOD repair. No intraoperative mortality occurred in either group. Postoperative renal, hepatic, and respiratory failure requiring tracheostomy was common in both groups. Survival to hospital discharge in both cohorts was 70%. Conclusions: Post-MI VSD repair with patch/SOD has comparable short-term outcomes with patch alone. Addition of a SOD to patch repair provides a scaffold that may enhance the repair of post-MI VSD with patch exclusion.

20.
AoB Plants ; 15(6): plad070, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38028747

RESUMEN

Identifying the factors that facilitate and limit invasive species' range expansion has both practical and theoretical importance, especially at the range edges. Here, we used reciprocal common garden experiments spanning the North/South and East/West range that include the North American core, intermediate and range edges of the globally invasive plant, Johnsongrass (Sorghum halepense) to investigate the interplay of climate, biotic interactions (i.e. competition) and patterns of adaptation. Our results suggest that the rapid range expansion of Johnsongrass into diverse environments across wide geographies occurred largely without local adaptation, but that further range expansion may be restricted by a fitness trade-off that limits population growth at the range edge. Interestingly, plant competition strongly dampened Johnsongrass growth but did not change the rank order performance of populations within a garden, though this varied among gardens (climates). Our findings highlight the importance of including the range edge when studying the range dynamics of invasive species, especially as we try to understand how invasive species will respond to accelerating global changes.

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