Heart-lung interations

Many animal species do not breathe in a continuous, rhythmic fashion, but rather display a variety of breathing patterns characterized by prolonged periods between breaths (inter-breath intervals), during which the heart continues to beat. Examples of intermittent breathing abound across the animal kingdom, from crustaceans to cetaceans. With respect to human physiology, intermittent breathing-also termed 'periodic' or 'episodic' breathing-is associated with a variety of pathologies. Cardiovascular phenomena associated with intermittent breathing in diving species have been termed 'diving bradycardia', 'submersion bradycardia', 'immersion bradycardia', 'ventilation tachycardia', 'respiratory sinus arrhythmia' and so forth...

PURPOSE: Within a multi-institutional project, we aimed to assess the transferability of knowledge-based (KB) plan prediction models in the case of whole breast irradiation (WBI) for left-side breast irradiation with tangential fields (TF). METHODS: Eight institutions set KB models, following previously shared common criteria. Plan prediction performance was tested on 16 new patients (2 pts per centre) extracting dose-volume-histogram (DVH) prediction bands of heart, ipsilateral lung, contralateral lung and breast...

Fuke Qianjin capsules (FKQJ) exhibit obvious advantages and characteristics in the treatment of pelvic inflammatory disease. At present, information regarding the in vivo process of FKQJ is lacking, which has become a bottleneck in further determining the therapeutic effect of this traditional Chinese medicine. In the present study, a sensitive, simple and reliable method was developed and validated for the simultaneous quantification of 12 main components (4 flavonoids, 4 alkaloids, 2 phthalides and 2 diterpene lactones) in plasma and seven tissues of rats to study the pharmacokinetic and distribution characteristics of these components in vivo by using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for the first time...

INTRODUCTION: Endomyocardial biopsy (EMB)-based traditional microscopy remains the gold standard for the detection of cardiac allograft rejection, despite its limitation of inherent subjectivity leading to inter-reader variability. Alternative techniques now exist to surveil for allograft injury and classify rejection. Donor-derived cell-free DNA (dd-cfDNA) testing is now a validated blood-based assay used to surveil for allograft injury. The molecular microscope diagnostic system (MMDx) utilizes intragraft rejection-associated transcripts (RATs) to classify allograft rejection and identify injury...

Acylcarnitines are metabolic intermediates of fatty acids and branched-chain amino acids having vital biofunctions and pathophysiological significances. Here, we developed a high-throughput method for quantifying hundreds of acylcarnitines in one run using ultrahigh performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS). This enabled simultaneous quantification of 1136 acylcarnitines (C0-C26) within 10-min with good sensitivity (limit of detection < 0.7 fmol), linearity (correlation coefficient > 0...

Glioblastoma (GBM) is a fast-growing and aggressive brain tumor which invades the nearby brain tissue but generally does not spread to the distant organs. Nonetheless, if untreated, GBM can result in patient death in time even less than few months from the diagnosis. The influence of the tumor progress on organs other than brain is obvious but still not well described. Therefore, we examined the elemental abnormalities appearing in selected body organs (kidney, heart, spleen, lung) in two rat models of GBM...

PURPOSE: Adagrasib is a selective and reversible inhibitor of KRAS G12C, which significantly delays the progression of solid tumors. However, the absorption, distribution, metabolism, and excretion of adagrasib in vivo are unclear. This study explores the absorption and distribution of adagrasib in vivo. METHODS: An ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-MS/MS) method was established for the determination of adagrasib in the rat plasma and tissue...

N-nitrosodimethylamine (NDMA) is classified as a human carcinogen and could be produced by both natural and industrial processes. Although its toxicity and histopathology have been well-studied in animal species, there is insufficient data on the blood and tissue exposures that can be correlated with the toxicity of NDMA. The purpose of this study was to evaluate gender-specific pharmacokinetics/toxicokinetics (PKs/TKs), tissue distribution, and excretion after the oral administration of three different doses of NDMA in rats using a physiologically-based pharmacokinetic (PBPK) model...

INTRODUCTION: Methotrexate (MTX), a folate antagonist, is often used as second-line treatment in patients with sarcoidosis. Effectiveness of MTX has large inter-patient variability and at present therapeutic drug monitoring (TDM) of MTX is not possible. Upon administration, MTX is actively transported into cells and metabolized to its active forms by adding glutamate residues forming MTXPG(n=1-5) resulting in enhanced cellular retention. In this study we address the question whether different MTXPG(n) concentrations in red blood cells (RBC) of patients with sarcoidosis after 3 months of MTX therapy correlate with response to treatment...

Pathogenic single-nucleotide variants (SNVs) and copy-number variant (CNV) deletions involving the FOXF1 transcription factor gene or CNV deletions of its distant lung-specific enhancer are responsible for alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), a rarely diagnosed lethal lung developmental disorder in neonates. In contrast to SNVs within FOXF1 and CNV deletions involving only the FOXF1 enhancer, larger-sized deletions involving FOXF1 and the adjacent, oppositely oriented lncRNA gene FENDRR have additionally been associated with hypoplastic left heart syndrome and single umbilical artery (SUA)...

AIMS: The popularity of B-line-guided congestion assessment by lung ultrasound (LUS) has been increasing. However, the ability of novice residents to detect residual congestion with B-line-guided assessment by LUS after decongestion treatment is poorly understood. In this study, we investigated whether novice residents (no prior echocardiography experience) can acquire the skills for B-line-guided residual congestion assessment and whether the range of variation in assessment is acceptable in actual clinical use...

BACKGROUND: Pulmonary antibody-mediated rejection is still a challenging diagnosis as C4d has poor sensitivity. Previous studies have indicated that the phosphorylated S6 ribosomal protein, a component of the mammalian target of rapamycin (mTOR) pathway, is correlated with de novo donor-specific antibodies in lung transplantation. The objective of this study was to evaluate the phosphorylation of S6 ribosomal protein as a surrogate for AMR diagnosis in lung transplant patients. METHODS: This multicentre retrospective study analyzed transbronchial biopsies from 216 lung transplanted patients, 114 with antibody-mediated rejection and 102 without (19 with acute cellular rejection, 17 with ischemia/reperfusion injury, 18 with infection, and 48 without post-transplant complications)...

PURPOSE/OBJECTIVE(S): In lung cancer radiation therapy, clinicians must outline the gross tumor volume (GTV) precisely on the planning computed tomography (pCT) for accurate radiation dose delivery. However, due to the limited contrast between tumor and normal tissues in lung parenchyma, accurate delineation of tumor boundaries is difficult leading to large inter-observer variation. In this study, we develop an anatomy-guided lung GTV deep segmentation model using a training cohort of multi-center datasets...

PURPOSE/OBJECTIVE(S): The deep inspiration breath-hold (DIBH) approach has been thoroughly researched with the aim of reducing radiation exposures to normal tissues in breast cancer patients. Although heart and lung toxicity are widely addressed in many literature, radiation-associated liver toxicity and dose constraints for the right coronary artery (RCA) are not well studied in relation to breast radiotherapy. Additionally, very few studies have investigated the relationship between doses to cardiac substructures...

PURPOSE/OBJECTIVE(S): to compare dosimetric parameters between Artificial intelligence (AI) generated organ at risks (OAR) and Radiation Oncologist approved OARs and evaluation of appropriateness unedited AI- OARs in routine clinical plan optimization and evaluation. MATERIALS/METHODS: The OARs (lung, spinal cord and heart) for twenty SBRT (stereotactic body radiotherapy) lung CT simulation datasets were derived by AI based segmentation algorithms. These AI- OARs were edited by a staff Radiation Oncologist and then subjected to our SBRT peer-review process at our institution...

PURPOSE/OBJECTIVE(S): To report the planning dummy run results of the POstmastectomy radioThErapy in Node posiTive breast cancer with or without Internal mAmmary nodaL irradiation (POTENTIAL) trial-a multicenter, randomized, phase 3 trial-to evaluate postmastectomy radiotherapy, with or without internal mammary nodal irradiation, for patients with high-risk breast cancer. MATERIALS/METHODS: All participating institutions were provided the contours of the dummy run case, and they generated radiotherapy (RT) plans per protocol guidelines...

BACKGROUND: Identifying novel epigenetic signatures associated with serum immunoglobulin E (IgE) may improve our understanding of molecular mechanisms underlying asthma and IgE-mediated diseases. METHODS: We performed an epigenome-wide association study using whole blood from Framingham Heart Study (FHS; n = 3,471, 46% females) participants and validated results using the Childhood Asthma Management Program (CAMP; n = 674, 39% females) and the Genetic Epidemiology of Asthma in Costa Rica Study (CRA; n = 787, 41% females)...

BACKGROUND: Knowledge-based planning (KBP) is a method for automated radiotherapy treatment planning where appropriate optimization objectives for new patients are predicted based on a library of training plans. KBP can save time and improve organ at-risk sparing and inter-patient consistency compared to manual planning, but its performance depends on the quality of the training plans. We used another system for automated planning, which generates multi-criteria optimized (MCO) plans based on a wish list, to create training plans for the KBP model, to allow seamless integration of knowledge from a new system into clinical routine...

BACKGROUND AND PURPOSE: Magnetic resonance imaging guided radiotherapy (MRgRT) offers treatment plan adaptation to the anatomy of the day. In the current MRgRT workflow, this requires the time consuming and repetitive task of manual delineation of organs-at-risk (OARs), which is also prone to inter- and intra-observer variability. Therefore, deep learning autosegmentation (DLAS) is becoming increasingly attractive. No investigation of its application to OARs in thoracic magnetic resonance images (MRIs) from MRgRT has been done so far...

BACKGROUND: COVID-19 patients undergoing ECMO are at highly increased risk of nosocomial infections. OBJECTIVES: To study incidence, clinical outcomes and microbiological features of bloodstream infections (BSI) occurring during ECMO in COVID-19 patients. METHODS: Observational prospective cohort study enrolling consecutive COVID-19 patients undergoing veno-venous-ECMO in an Italian ICU from March 2020 to March 2022. RESULTS: In the study population of 68 patients (age 53 [49-60] years, 82% males), 30 (44%) developed bloodstream infections (BSI group) while 38 did not (N-BSI group) with an incidence of 32 events/1000 days of ECMO...