RESUMEN
BACKGROUND: Noroviruses are an important viral cause of chronic diarrhea in immunocompromised individuals. METHOD: We collected norovirus-positive stool samples (n=448) from immunocompromised patients (n=88) at the National Institutes of Health Clinical Research Center, U.S. from 2010-2022. We assessed clinical characteristics of the cohort, norovirus molecular epidemiology, and infectivity of norovirus specimens in human intestinal enteroids (HIEs) monolayers. RESULTS: Thirty-nine of the 88 patients had sequential stool samples that allowed documentation of chronic norovirus infection with shedding levels ranging from 104 to 1011 genome copies/g of stool. The majority with confirmed chronic norovirus infection in this cohort (32/39, 82%) had clinical evidence of an inborn error of immunity (13 identified monogenic diseases), most with combined immunodeficiency (15 of 32) or common variable immunodeficiency (11 of 32). Noroviruses detected in the cohort were genetically diverse: both Genogroup I (GI.2, GI.3, GI.5, and GI.6) and Genogroup II (GII.1-GII.4, GII.6, GII.7, GII.12, GII.14, and GII.17) genotypes were detected, with GII.4 variants (Osaka, Apeldoorn, Den Haag, New Orleans, and Sydney) predominant (51 of 88, 57.9%). Viruses belonging to the GII.4 Sydney variant group that replicated in HIEs (n=9) showed a higher fold-increase in RNA genome copies during infection compared to others that replicated. CONCLUSIONS: Genetically and biologically diverse noroviruses established chronic infection in individuals with both inborn and acquired immunologic defects enrolled in an NIH surveillance study spanning 12 years, demonstrating the unique nature of each virus and host interaction.
RESUMEN
OBJECTIVE: Highly-undersampled, dynamic MRI reconstruction, particularly in multi-coil scenarios, is a challenging inverse problem. Unrolled networks achieve state-of-the-art performance in MRI reconstruction but suffer from long training times and extensive GPU memory cost. METHODS: In this work, we propose a novel training strategy for IMplicit UNrolled NEtworks (IMUNNE) for highly-undersampled, multi-coil dynamic MRI reconstruction. It formulates the MRI reconstruction problem as an implicit fixed-point equation and leverages gradient approximation for backpropagation, enabling training of deep architectures with fixed memory cost. This study represents the first application of implicit network theory in the context of real-time cine MRI. The proposed method is evaluated using a prospectively undersampled, real-time cine dataset using radial k-space sampling, comprising balanced steady-state free precession (b-SSFP) readouts. Experiments include a hyperparameter search, head-to-head comparisons with a complex U-Net (CU-Net) and an alternating unrolled network (Alt-UN), and an analysis of robustness under noise perturbations; peak signal-to-noise ratio, structural similarity index, normalized root mean-square error, spatio-temporal entropic difference, and a blur metric were used. RESULTS: IMUNNE produced significantly and slightly better image quality compared to CU-Net and Alt-UN, respectively. Compared with Alt-UN, IMUNNE significantly reduced training and inference times, making it a promising approach for highly-accelerated, multi-coil real-time cine MRI reconstruction. CONCLUSION: IMUNNE strategy successfully applies unrolled networks to image reconstruction of highly-accelerated, real-time radial cine MRI. SIGNIFICANCE: Implicit training enables rapid, high-quality, and cost-effective CMR exams by reducing training and inference times and lowering memory cost associated with advanced reconstruction methods.
RESUMEN
PURPOSE: To assess the technical feasibility and safety of image-guided percutaneous biphasic monopolar pulsed electric field (PEF) ablation of primary and metastatic tumors. METHODS AND METHODS: With IRB approval and HIPAA compliance, this retrospective, single-institution study cohort of 17 patients (mean age: 53.5 years, range: 20 - 94 years) with overall progressive disease underwent 26 PEF ablation procedures for 30 metastatic (90%) and primary (10%) target lesions in the thorax (n=20), abdomen (n=7), and head and neck (n=3). Concurrent systemic therapy was used in 14/17 patients (82%). Follow-up imaging was scheduled for 1, 3, and 6 months after PEF ablation, and target and off-target lesion sizes were recorded. The overall response was assessed by the RECIST 1.1 criteria with imaging immediately before PEF serving as baseline. Adverse events (AEs) were determined by the Society of Interventional Radiology classification. RESULTS: PEF ablation procedures were well tolerated and technically feasible for all 17 of 17 patients. The mean initial size of the target and off-target tumors were 2.6±1.5 cm (range: 0.4 - 6.9cm) and 2.2±1.1 cm (range: 1.0 - 5.2cm), respectively. Overall, 15/30 (50%) target lesions and 12/24 (50%) off-target lesions were unchanged or decreased in size at the patient's last follow-up. Eight patients had overall stable disease (47%) at the last follow-up. There were nine mild (9/26, 35%) and one moderate (1/26, 4%) AE. CONCLUSION: All PEF procedures were technically feasible with one moderate AE and stable disease for 47% of patients with a median follow-up period of three months.
RESUMEN
Late perforation of the ileum is a rare and potentially life-threatening complication following intestinal resection. We present a unique case of a woman in her 60s with a history of appendiceal carcinoid tumour, who underwent a right hemicolectomy. Positron emission tomography and surveillance CTs showed normal surgical changes and no recurrent malignancy. Three years postoperatively, she presented with severe abdominal pain. CT revealed a perforation along the ileal wall of the ileocolonic anastomosis. She underwent emergent resection and repeat ileocolonic anastomosis. We conclude that the patient had subclinical ischaemia of the anastomosis, which eventually progressed to perforation 3 years later. We discuss a literature review on late small intestinal anastomotic perforations and their associated risk factors. Our case and literature review emphasise the importance of considering delayed anastomotic leak in postoperative patients with a history of intestinal cancer, inflammatory bowel disease, Roux-en-Y enteroenterostomy or side-to-side anastomosis.
Asunto(s)
Anastomosis Quirúrgica , Íleon , Perforación Intestinal , Humanos , Femenino , Perforación Intestinal/etiología , Perforación Intestinal/cirugía , Perforación Intestinal/diagnóstico por imagen , Anastomosis Quirúrgica/efectos adversos , Persona de Mediana Edad , Íleon/cirugía , Colectomía/efectos adversos , Tumor Carcinoide/cirugía , Neoplasias del Apéndice/cirugía , Complicaciones Posoperatorias/cirugía , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/diagnóstico por imagen , Fuga Anastomótica/cirugía , Fuga Anastomótica/etiología , Tomografía Computarizada por Rayos X , Dolor Abdominal/etiologíaRESUMEN
BACKGROUND: Particulate matter exposure (PM) is a cause of aerodigestive disease globally. The destruction of the World Trade Center (WTC) exposed first responders and inhabitants of New York City to WTC-PM and caused obstructive airways disease (OAD), gastroesophageal reflux disease (GERD) and Barrett's Esophagus (BE). GERD not only diminishes health-related quality of life but also gives rise to complications that extend beyond the scope of BE. GERD can incite or exacerbate allergies, sinusitis, bronchitis, and asthma. Disease features of the aerodigestive axis can overlap, often necessitating more invasive diagnostic testing and treatment modalities. This presents a need to develop novel non-invasive biomarkers of GERD, BE, airway hyperreactivity (AHR), treatment efficacy, and severity of symptoms. METHODS: Our observational case-cohort study will leverage the longitudinally phenotyped Fire Department of New York (FDNY)-WTC exposed cohort to identify Biomarkers of Airway Disease, Barrett's and Underdiagnosed Reflux Noninvasively (BAD-BURN). Our study population consists of n = 4,192 individuals from which we have randomly selected a sub-cohort control group (n = 837). We will then recruit subgroups of i. AHR only ii. GERD only iii. BE iv. GERD/BE and AHR overlap or v. No GERD or AHR, from the sub-cohort control group. We will then phenotype and examine non-invasive biomarkers of these subgroups to identify under-diagnosis and/or treatment efficacy. The findings may further contribute to the development of future biologically plausible therapies, ultimately enhance patient care and quality of life. DISCUSSION: Although many studies have suggested interdependence between airway and digestive diseases, the causative factors and specific mechanisms remain unclear. The detection of the disease is further complicated by the invasiveness of conventional GERD diagnosis procedures and the limited availability of disease-specific biomarkers. The management of reflux is important, as it directly increases risk of cancer and negatively impacts quality of life. Therefore, it is vital to develop novel noninvasive disease markers that can effectively phenotype, facilitate early diagnosis of premalignant disease and identify potential therapeutic targets to improve patient care. TRIAL REGISTRATION: Name of Primary Registry: "Biomarkers of Airway Disease, Barrett's and Underdiagnosed Reflux Noninvasively (BADBURN)". Trial Identifying Number: NCT05216133 . Date of Registration: January 31, 2022.
Asunto(s)
Esófago de Barrett , Biomarcadores , Bomberos , Reflujo Gastroesofágico , Ataques Terroristas del 11 de Septiembre , Humanos , Esófago de Barrett/diagnóstico , Esófago de Barrett/etiología , Reflujo Gastroesofágico/diagnóstico , Biomarcadores/sangre , Estudios de Casos y Controles , Bomberos/estadística & datos numéricos , Ciudad de Nueva York , Exposición Profesional/efectos adversos , Material Particulado/efectos adversos , Material Particulado/análisis , Estudios Observacionales como Asunto , MasculinoRESUMEN
BACKGROUND: Large-scale data on incidental premature ventricular contraction (PVC) prevalence and morphologies have been lacking, leaving many providers without guidance on further cardiac testing for patients with incidental PVCs on ECG. Athletes offer an intriguing cohort to understand the clinical significance, prevalence, and common morphologies of incidental PVCs because they often undergo ECG screening during preparticipation exams. METHODS: Digital ECGs were obtained from 10â 728 screened athletes aged 14 to 35 years during mass screenings in schools and professional sports teams between 2014 and 2021. A retrospective analysis of ECGs with PVCs was performed using the simultaneous display of frontal (limb) and horizontal (precordial) plane leads. PVCs were coded for morphology and categorized as benign or nonbenign using recommended criteria. RESULTS: Twenty-six athletes (0.24%) were found to have at least 1 PVC. Among these, 50% were female, 65% were White, 8% were Asian, 4% were Hispanic, and 23% were Black. Nineteen of the 26 (73%) ECGs had PVCs with a left bundle branch block pattern compared with 7 (27%) with a right bundle branch block pattern. Twenty-four ECGs (96%) had PVCs with benign patterns, including 18 with right ventricular outflow tract, 5 with left anterior fascicle, and 2 with left posterior fascicle morphology. CONCLUSIONS: There is a low prevalence of PVCs on routine ECG screening of young athletes, and most PVCs are of benign morphology in this population. This study highlights the value of using digital ECG recorders with simultaneous lead display to guide decision-making about further cardiac testing and referrals in young athletes with PVCs. Using our results and review of the literature, we propose methods and algorithms of PVC evaluation on screening ECGs to help guide many providers with risk stratification and decision-making about further cardiac testing and electrophysiology referrals in young athletes with PVCs.
RESUMEN
Environmental exposure-associated disease is an active area of study, especially in the context of increasing global air pollution and use of inhalants. Our group is dedicated to the study of exposure-related inflammation and downstream health effects. While many studies have focused on the impact of inhalants on respiratory sequelae, there is growing evidence of the involvement of other systems including autoimmune, endocrine, and gastrointestinal. This systematic review aims to provide a recent update that will underscore the associations between inhalation exposures and upper gastrointestinal disease in the contexts of our evolving environmental exposures. Keywords focused on inhalational exposures and gastrointestinal disease. Primary search identified n = 764 studies, of which n = 64 met eligibility criteria. In particular, there was support for existing evidence that PM increases the risk of upper gastrointestinal diseases. Smoking was also confirmed to be major risk factor. Interestingly, studies in this review have also identified waterpipe use as a significant risk factor for gastroesophageal reflux and gastric cancer. Our systematic review identified inhalational exposures as risk factors for aerodigestive disease, further supporting the association between environmental exposure and digestive disease. However, due to limitations on our review's scope, further studies must be done to better understand this interaction.
RESUMEN
OBJECTIVE: Although point of care ultrasound (POCUS) use has become prevalent in medicine, clinicians may not be familiar with the evidence supporting its utility in patient care. The objective of this study is to identify the top five most influential papers published on the use of cardiac POCUS and lung POCUS in adult patients. METHODS: A 14-member expert panel from the Canadian Association of Emergency Physicians (CAEP) Emergency Ultrasound Committee and the Canadian Ultrasound Fellowship Collaborative used a modified Delphi process. Panel members are ultrasound fellowship trained or equivalent, are engaged in POCUS scholarship, and are leaders in POCUS locally and nationally in Canada. The modified Delphi process consisted of three rounds of sequential surveys and discussion to achieve consensus on the top five most influential papers on cardiac POCUS and lung POCUS. RESULTS: A total of 66 relevant papers on cardiac POCUS and 68 relevant papers on lung POCUS were nominated by the panel. There was 100% participation by the panel members in all three rounds of the modified Delphi process. At the end of this process, we identified the top five most influential papers on cardiac POCUS and lung POCUS. Papers include studies supporting the use of POCUS for accurately assessing left ventricular systolic function, diagnosing pericardial effusion, clarifying its test characteristics for pulmonary embolism, identifying pulmonary edema and pneumonia, as well as consensus statements on the use of cardiac and lung POCUS in clinical practice. CONCLUSION: We have created a list of the top five influential papers on cardiac POCUS and lung POCUS as an evidence-based resource for trainees, clinicians, and researchers. This will help trainees and clinicians better understand how to use POCUS when scanning the heart and lungs, and it will also help researchers better understand where to direct their scholarly efforts with future research.
RéSUMé: OBJECTIF: Bien que l'utilisation de l'échographie par point de soins (POCUS) soit devenue courante en médecine, les cliniciens ne sont peut-être pas familiarisés avec les données probantes qui appuient son utilité dans les soins aux patients. Cette étude a pour objectif d'identifier les cinq articles les plus influents publiés sur l'utilisation de la POCUS cardiaque et pulmonaire chez des patients adultes. MéTHODES: Un groupe d'experts composé de 14 membres du Comité des échographies d'urgence de l'Association canadienne des médecins d'urgence (ACEP) et du Canadian Ultrasound Fellowship Collaborative a utilisé un processus Delphi modifié. Les membres du comité sont des stagiaires en échographie ou l'équivalent, ils participent à des activités de recherche sur le POCUS et sont des chefs de file au niveau local et national au Canada. Le processus Delphi modifié consistait en trois rondes de sondages séquentiels et de discussions pour parvenir à un consensus sur les cinq articles les plus influents sur la POCUS cardiaque et la POCUS pulmonaire. RéSULTATS: Le panel a proposé un total de 66 articles pertinents sur la POCUS cardiaque et 68 documents pertinents sur la POCUS pulmonaire. Les membres du groupe ont participé à 100 % aux trois rondes du processus Delphi modifié. À la fin de ce processus, nous avons identifié les cinq principaux articles les plus influents sur le POCUS cardiaque et le POCUS pulmonaire. Les articles comprennent des études soutenant l'utilisation de POCUS pour évaluer avec précision la fonction systolique du ventricule gauche, diagnostiquer le épanchement péricardique, clarifier ses caractéristiques de test pour l'embolie pulmonaire, identifier l'Ådème pulmonaire et la pneumonie, ainsi que des déclarations de consensus sur l'utilisation du POCUS cardiaque et pulmonaire dans la pratique clinique. CONCLUSION: Nous avons dressé une liste des cinq principaux articles influents sur le POCUS cardiaque et le POCUS pulmonaire en tant que ressource fondée sur des données probantes pour les stagiaires, les cliniciens et les chercheurs. Cela aidera les stagiaires et les cliniciens à mieux comprendre comment utiliser le POCUS pour scanner le cÅur et les poumons, et cela aidera également les chercheurs à mieux comprendre où orienter leurs efforts scientifiques dans la recherche future.
RESUMEN
PURPOSE: To investigate the effect of patient and tumor-specific characteristics on the size of immediate phase lung microwave ablation (MWA) zone and establish a prediction model. METHODS AND MATERIALS: This IRB-approved, HIPAA compliant cohort included 164 lesions from 99 patients who underwent CT-guided lung MWA and the two-dimensional elliptical ground-glass opacity ablation zone was measured. Duration, maximum temperature, tumor depth, presence of emphysema, history of ipsilateral lung ablation, surgery, and radiation were recorded. K-fold cross validation with k=5 and Least Absolute Shrinkage and Selection Operator were used to build prediction models for the major and minor axes, and area of the ablation zone. RESULTS: The median of immediate phase ablation duration was 2 minutes (IQR: 1.5 - 4.25) with 65W of power for all ablations. The mean major, minor axes, and area of ablation zone were 3.1±0.6cm, 2.0±0.5cm, and 5.1±2.1cm2. The major axis, minor axis, and area of immediate phase ablation zone dimensions were significantly associated with duration (p<0.001, p<0.001, p<0.001), maximum temperature (p<0.001, p<0.001, p<0.001), tumor depth (p=0.387, p<0.001, p<0.001), history of ipsilateral lung ablation (p=0.008, p=0.286, p=0.076), and lung radiation (p=0.001, p=0.042, p=0.015). The prediction model showed R2 values for major and minor axes and area of the ablation zone to be 0.50, 0.45, and 0.53, respectively. CONCLUSION: Duration, maximum temperature, tumor depth, history of ipsilateral lung ablation, surgery, and radiation were significantly associated with the ablation zone dimensions and size and can be used to build the prediction model to approximate the immediate phase lung MWA zone.
RESUMEN
Purpose: Aqueous humor inflow rate, a key parameter influencing aqueous humor dynamics, is typically measured by fluorophotometery. Analyzing fluorophotometric data depends, inter alia, on the volume of aqueous humor in the anterior, but not the posterior, chamber. Previous fluorophotometric studies of aqueous inflow rate in mice have assumed the ratio of anterior:posterior volumes in mice to be similar to those in humans. Our goal was to measure anterior and posterior chamber volumes in mice to facilitate better estimates of aqueous inflow rates. Methods: We used standard near-infrared optical coherence tomography (OCT) and robotic visible-light OCT (vis-OCT) to visualize, reconstruct and quantify the volumes of the anterior and posterior chambers of the mouse eye in vivo. We used histology and micro-CT scans to validate relevant landmarks from ex vivo tissues to facilitate in vivo measurement. Results: Posterior chamber volume is 1.1 times the anterior chamber volume in BALB/cAnNCrl mice, i.e. the anterior chamber constitutes about 47% of the total aqueous humor volume, which is very dissimilar to the situation in humans. Anterior chamber volumes in 2-month-old BALB/cAnNCrl and 7-month-old C57BL6/J mice were 1.55 ± 0.36 µL (n=10) and 2.41 ± 0.29 µL (n=8), respectively. This implies that previous studies likely over-estimated aqueous inflow rate by approximately two-fold. Conclusions: It is necessary to reassess previously reported estimates of aqueous inflow rates, and thus aqueous humor dynamics in the mouse. For example, we now estimate that only 0-15% of aqueous humor drains via the pressure-independent (unconventional) route, similar to that seen in humans and monkeys.
RESUMEN
The "International Society for Heart and Lung Transplantation Guidelines for the Evaluation and Care of Cardiac Transplant Candidates-2024" updates and replaces the "Listing Criteria for Heart Transplantation: International Society for Heart and Lung Transplantation Guidelines for the Care of Cardiac Transplant Candidates-2006" and the "2016 International Society for Heart Lung Transplantation Listing Criteria for Heart Transplantation: A 10-year Update." The document aims to provide tools to help integrate the numerous variables involved in evaluating patients for transplantation, emphasizing updating the collaborative treatment while waiting for a transplant. There have been significant practice-changing developments in the care of heart transplant recipients since the publication of the International Society for Heart and Lung Transplantation (ISHLT) guidelines in 2006 and the 10-year update in 2016. The changes pertain to 3 aspects of heart transplantation: (1) patient selection criteria, (2) care of selected patient populations, and (3) durable mechanical support. To address these issues, 3 task forces were assembled. Each task force was cochaired by a pediatric heart transplant physician with the specific mandate to highlight issues unique to the pediatric heart transplant population and ensure their adequate representation. This guideline was harmonized with other ISHLT guidelines published through November 2023. The 2024 ISHLT guidelines for the evaluation and care of cardiac transplant candidates provide recommendations based on contemporary scientific evidence and patient management flow diagrams. The American College of Cardiology and American Heart Association modular knowledge chunk format has been implemented, allowing guideline information to be grouped into discrete packages (or modules) of information on a disease-specific topic or management issue. Aiming to improve the quality of care for heart transplant candidates, the recommendations present an evidence-based approach.
RESUMEN
Aims: To determine whether paediatric congenital heart disease (CHD) patients with epicardial cardiac implantable electronic devices (CIEDs) receive high cumulative effective doses (CEDs) of ionizing radiation from medical imaging tests. Methods and results: We compared 28 paediatric CHD patients with epicardial CIEDs (cases) against 40 patients with no CIED matched by age at operation, sex, surgical era, and CHD diagnosis (controls). We performed a retrospective review of radiation exposure from medical imaging exams between 2006 and 2022. Radiation dose from computed tomography (CT) and X-ray radiography was calculated using the National Cancer Institute Radiation Dosimetry Tool. We performed univariate analysis to compare the CED between the two groups. In the case subgroup, we convened experts' review to adjudicate the prevalence of CT exams that should have been performed with magnetic resonance imaging (MRI) in the absence of a CIED. Children (median age 2.5 years at implant) with CIEDs received significantly higher median CED compared with matched controls (6.90 vs. 1.72 mSv, P = 0.0018). In cases, expert adjudication showed that 80% of the CT exams would have been performed with MRI in the absence of a CIED. This resulted, on average, a five-fold increase in the effective dose (ED) from post-lead implant CTs. Conclusion: Paediatric CHD patients with CIED received four times higher CED than matched controls. Improved access to medical imaging tests without ionizing radiation, such as MRI, could potentially reduce the ED in CIED patients by up to five times.
RESUMEN
[This corrects the article DOI: 10.3389/fnana.2024.1385932.].
RESUMEN
INTRODUCTION: Osteotomies are routinely incorporated in rhinoplasty, however, the influence of mass, velocity, kinetic energy (KE), and momentum (p) of the mallet on fracture patterns has not been studied. METHODS: An experimental sledge guillotine setup was designed simulating a mallet strike with adjustable height and mass and 2 mm-thick Sawbone blocks. KE and p were calculated using KE = ½ mass × velocity2 and p = mass × velocity formulas. Fracture lengths and angles were measured. RESULTS: Ten groups with varying mallet masses and drop heights were tested with 10 bones per group. Fracture length positively correlated with KE (R = 0.542, p < 0.001) and p (R = 0.508, p < 0.001). Fracture angle also positively correlated with KE (R = 0.367, p < 0.001) and p (R = 0.329, p < 0.001). In groups with similar KE, osteotomies with higher p (heavier mallet with slower velocity) had greater fracture lengths (29.31 ± 0.68 vs. 27.68 ± 2.12 mm, p = 0.013) but similar fracture angles (p = 0.189). In groups with similar p, osteotomies with higher KE (lighter hammer with faster velocity) had significantly greater fracture lengths (28.28 ± 1.28 vs. 20.45 ± 12.20 mm, p = 0.041) and greater divergent fracture angles (3.13 ± 1.97° vs. 1.40 ± 1.36°, p = 0.031). Regression modeling of the relationship between KE and fracture lengths and angles demonstrated that cubic followed by logarithmic regression models had the best fits. CONCLUSION: Osteotomy fracture patterns positively correlated with the mallet's KE more so than its p, suggesting that the mallet's velocity has an increased impact effect than its mass. Clinically, a heavier mallet with a lower velocity will likely generate a smaller fracture length and fracture angle, indicating a more controlled and ideal fracture. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.
RESUMEN
Cardiac allograft vasculopathy (CAV) is a leading cause of death after heart transplantation (HT). We evaluated donor-derived cell-free DNA (dd-cfDNA) as a noninvasive biomarker of CAV development after HT. The INSPIRE registry at the Intermountain Medical Center was queried for stored plasma samples from HT patients with and without CAV. At Stanford University, HT patients with CAV (cases) and without CAV (controls) were enrolled prospectively, and blood samples were collected. All the samples were analyzed for dd-cfDNA using the AlloSure assay (CareDx, Inc.). CAV was defined per the ISHLT 2010 standardized classification system. Univariate associations between patient demographics and clinical characteristics and their CAV grade were tested using chi-square and Wilcoxon rank sum tests. Associations between their dd-cfDNA levels and CAV grades were examined using a nonparametric Kruskal-Wallis test. A total of 69 pts were included, and 101 samples were analyzed for dd-cfDNA. The mean age at sample collection was 58.6 ± 13.7 years; 66.7% of the patients were male, and 81% were White. CAV 0, 1, 2, and 3 were present in 37.6%, 22.8%, 22.8%, and 16.8% of included samples, respectively. The median dd-cfDNA level was 0.13% (0.06, 0.33). The median dd-cfDNA level was not significantly different between CAV (-) and CAV (+): 0.09% (0.05%-0.32%) and 0.15% (0.07%-0.33%), respectively, p = 0.25 and with similar results across all CAV grades. In our study, dd-cfDNA levels did not correlate with the presence of CAV and did not differ across CAV grades. As such, dd-cfDNA does not appear to be a reliable noninvasive biomarker for CAV surveillance.
Asunto(s)
Biomarcadores , Ácidos Nucleicos Libres de Células , Trasplante de Corazón , Donantes de Tejidos , Humanos , Masculino , Femenino , Trasplante de Corazón/efectos adversos , Ácidos Nucleicos Libres de Células/sangre , Persona de Mediana Edad , Estudios de Seguimiento , Estudios Prospectivos , Biomarcadores/sangre , Pronóstico , Factores de Riesgo , Aloinjertos , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Estudios de Casos y Controles , Rechazo de Injerto/etiología , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/sangre , Supervivencia de Injerto , Enfermedades Vasculares/etiología , Enfermedades Vasculares/sangre , AdultoRESUMEN
BACKGROUND: Pig-tailed macaques (PTMs) are commonly used as preclinical models to assess antiretroviral drugs for HIV prevention research. Drug toxicities and disease pathologies are often preceded by changes in blood hematology. To better assess the safety profile of pharmaceuticals, we defined normal ranges of hematological values in PTMs using an Isolation Forest (iForest) algorithm. METHODS: Eighteen female PTMs were evaluated. Blood was collected 1-24 times per animal for a total of 159 samples. Complete blood counts were performed, and iForest was used to analyze the hematology data to detect outliers. RESULTS: Median, IQR, and ranges were calculated for 13 hematology parameters. From all samples, 22 outliers were detected. These outliers were excluded from the reference index. CONCLUSIONS: Using iForest, we defined a normal range for hematology parameters in female PTMs. This reference index can be a valuable tool for future studies evaluating drug toxicities in PTMs.
Asunto(s)
Algoritmos , Macaca nemestrina , Animales , Femenino , Valores de Referencia , Pruebas Hematológicas/veterinariaRESUMEN
BACKGROUND: On 20 September 2022, the Ugandan Ministry of Health declared an outbreak of Ebola disease caused by Sudan ebolavirus. METHODS: From 6 October 2022 to 10 January 2023, Centers for Disease Control and Prevention (CDC) staff conducted public health assessments at five US ports of entry for travellers identified as having been in Uganda in the past 21 days. CDC also recommended that state, local and territorial health departments ('health departments') conduct post-arrival monitoring of these travellers. CDC provided traveller contact information, daily to 58 health departments, and collected health department data regarding monitoring outcomes. RESULTS: Among 11 583 travellers screened, 132 (1%) required additional assessment due to potential exposures or symptoms of concern. Fifty-three (91%) health departments reported receiving traveller data from CDC for 10 114 (87%) travellers, of whom 8499 (84%) were contacted for monitoring, 1547 (15%) could not be contacted and 68 (1%) had no reported outcomes. No travellers with high-risk exposures or Ebola disease were identified. CONCLUSION: Entry risk assessment and post-arrival monitoring of travellers are resource-intensive activities that had low demonstrated yield during this and previous outbreaks. The efficiency of future responses could be improved by incorporating an assessment of risk of importation of disease, accounting for individual travellers' potential for exposure, and expanded use of methods that reduce burden to federal agencies, health departments, and travellers.
Asunto(s)
Brotes de Enfermedades , Fiebre Hemorrágica Ebola , Viaje , Humanos , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/prevención & control , Uganda/epidemiología , Brotes de Enfermedades/prevención & control , Medición de Riesgo/métodos , Estados Unidos/epidemiología , Masculino , Femenino , Adulto , Centers for Disease Control and Prevention, U.S. , Salud Pública/métodos , Persona de Mediana Edad , Ebolavirus , Adolescente , Adulto JovenRESUMEN
We herein report a fundamental mechanistic investigation into photochemical metal-nitrenoid generation and inner-sphere transposition reactivity using organometallic photoprecursors. By designing Cp*Ir(hydroxamate)(Ar) complexes, we induced photo-initiated ligand activation, allowing us to explore the amidative σ(Ir-aryl) migration reactivity. A combination of experimental mechanistic studies, femtosecond transient absorption spectroscopy, and density functional theory (DFT) calculations revealed that the metal-to-ligand charge transfer enables the σ(N-O) cleavage, followed by Ir-acylnitrenoid generation. The final inner-sphere σ(Ir-aryl) group migration results in a net amidative group transposition.