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Scientific Reports Dec 2023Rapid and precise intraoperative diagnosing systems are required for improving surgical outcomes and patient prognosis. Because of the poor quality and time-intensive...
Deep UV-excited fluorescence microscopy installed with CycleGAN-assisted image translation enhances precise detection of lymph node metastasis towards rapid intraoperative diagnosis.
Rapid and precise intraoperative diagnosing systems are required for improving surgical outcomes and patient prognosis. Because of the poor quality and time-intensive process of the prevalent frozen section procedure, various intraoperative diagnostic imaging systems have been explored. Microscopy with ultraviolet surface excitation (MUSE) is an inexpensive, maintenance-free, and rapid imaging technique that yields images like thin-sectioned samples without sectioning. However, pathologists find it nearly impossible to assign diagnostic labels to MUSE images of unfixed specimens; thus, AI for intraoperative diagnosis cannot be trained in a supervised learning manner. In this study, we propose a deep-learning pipeline model for lymph node metastasis detection, in which CycleGAN translate MUSE images of unfixed lymph nodes to formalin-fixed paraffin-embedded (FFPE) sample, and diagnostic prediction is performed using deep convolutional neural network trained on FFPE sample images. Our pipeline yielded an average accuracy of 84.6% when using each of the three deep convolutional neural networks, which is a 18.3% increase over the classification-only model without CycleGAN. The modality translation to FFPE sample images using CycleGAN can be applied to various intraoperative diagnostic imaging systems and eliminate the difficulty for pathologists in labeling new modality images in clinical sites. We anticipate our pipeline to be a starting point for accurate rapid intraoperative diagnostic systems for new imaging modalities, leading to healthcare quality improvement.
Topics: Humans; Lymphatic Metastasis; Alprostadil; Neural Networks, Computer; Microscopy, Fluorescence
PubMed: 38049475
DOI: 10.1038/s41598-023-48319-7 -
Medicine Oct 2023It is rare for newly diagnosed (de novo) or newly treated acute myeloid leukemia (AML) complicated with thrombotic complications, especially combined arterial and venous...
BACKGROUND
It is rare for newly diagnosed (de novo) or newly treated acute myeloid leukemia (AML) complicated with thrombotic complications, especially combined arterial and venous thrombosis.
METHODS
We reported a 13-year-old boy diagnosed with AML and leukocytosis, who developed right femoral vein and right dorsal artery thrombosis during chemotherapy. After treatment with low molecular weight heparin, diosmin, and alprostadil, symptoms were relieved. Unfortunately, the child suffered from coagulopathy afterward, which was unexpectedly caused by vitamin K deficiency.
RESULTS
After supplementation with vitamin K and prothrombin complex concentrate, coagulation function recovered.
CONCLUSION
For childhood AML patients with high thrombotic risks, close monitoring during anticoagulant treatment was necessary. Concomitantly, we should be alert to past medication history and combined medication use, especially those that may lead to vitamin K deficiency, secondary bleeding, and coagulation disorders. Rational use of antibiotics, anticoagulants, and antitumor drugs must be guaranteed.
Topics: Male; Humans; Child; Adolescent; Femoral Vein; Anticoagulants; Thrombosis; Blood Coagulation Disorders; Leukemia, Myeloid, Acute; Vitamin K Deficiency; Arteries
PubMed: 37832057
DOI: 10.1097/MD.0000000000035121 -
Academic Radiology Mar 2024To investigate if the combination of multishot diffusion imaging-based multiplexed sensitivity encoding intravoxel incoherent motion (MUSE-IVIM) and dynamic...
RATIONALE AND OBJECTIVES
To investigate if the combination of multishot diffusion imaging-based multiplexed sensitivity encoding intravoxel incoherent motion (MUSE-IVIM) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is feasible for staging Crohn's disease (CD) activity.
MATERIALS AND METHODS
A total of 65 CD patients were enrolled and analyzed in this retrospective study. The simplified endoscopic score for Crohn's disease (SES-CD) and magnetic resonance index of activity (MaRIA) were used as the reference. The MUSE-IVIM and DCE-MRI data were acquired at 3.0-T MRI scanner and processed by two radiologists. Three MUSE-IVIM parameters: fast apparent diffusion coefficient (ADC), slow apparent diffusion coefficient (ADC), and the fractional perfusion (Fraction of ADC), as well as four DCE-MRI parameters: volume transfer constant (K), rate constant (K), extravascular extracellular volume fraction (V), and plasma volume fraction (V) were generated. Intraclass correlation coefficient (ICC), non-parametric test (Kruskal-Wallis H and Mann-Whitney U), logistic regression, receiver operating characteristic analysis, Delong test, and Spearman's correlation test were performed.
RESULTS
According to SES-CD, 116 ileocolonic segments with CD lesions were identified as: inactive, mild, and moderate to severe. With multivariable logistic regression analysis, ADC (p < 0.001), Fraction of ADC (p = 0.005), K (p < 0.001) and K (p = 0.003) were identified as significant factors for differentiating among the three groups. Binary logistic analyses identified ADC (p = 0.001), K (p = 0.014), and K (p = 0.029) as independent predictors for the active status. The combination of ADC, K, and K performed better than MaRIA score (p = 0.028), for differentiating inactive and active status. MaRIA score was positively correlated with ADC (p < 0.001), K (p < 0.001), K (p < 0.001), and V (p = 0.001), however, negatively correlated with Fraction of ADC (p < 0.001).
CONCLUSION
The combination of MUSE-IVIM and DCE-MRI has been demonstrated to accurately stage inflammatory activity in CD.
Topics: Humans; Alprostadil; Multiparametric Magnetic Resonance Imaging; Crohn Disease; Retrospective Studies; Contrast Media; Magnetic Resonance Imaging; Diffusion Magnetic Resonance Imaging
PubMed: 37730492
DOI: 10.1016/j.acra.2023.08.028 -
BJUI Compass Jan 2024To investigate the risk factors for penile arterial insufficiency (PAI), which is a known cause of erectile dysfunction (ED).
OBJECTIVE
To investigate the risk factors for penile arterial insufficiency (PAI), which is a known cause of erectile dysfunction (ED).
METHODS
Patients who attended our urology clinic complaining of ED for more than 6 months were prospectively enrolled in this study over 1-year period. Patient consent was taken and ethical committee approval. Complete medical history and thorough general and local examination including body mass index (BMI), Peyronie's disease (PD) and penile size measurements (length and girth) were done for all of them. Laboratory tests included testosterone, lipid profile and glycated haemoglobin (HA1c). A penile duplex ultrasound study (PDU) was done for all patients after intracavernosal injection (ICI) with alprostadil. Peak systolic velocity (PSV) and end-diastolic velocity (EDV) were measured after 15 min. Statistical analysis was done using SPSS.
RESULTS
A total of 440 patients were enrolled in this analysis. The mean age was 48(23-81), and the mean BMI was 30 (18-51). Older patients had lower PSV ( = -0.361, = 0.000) and higher EDV ( = 0.174, = 0.001), and both correlations were highly statistically significant. Diabetics had lower PSV ( = -0.318, = 0.000) and higher EDV ( = 0.139, = 0.008), which were also highly statistically significant. Smokers had lower PSV ( = -0.140, = 0.008) and higher EDV ( = 0.178, = 0.001), which were highly statistically significant. Men with larger penises measured skin to tip had lower EDV ( = -0.119, = 0.024), which was less significant. Interestingly, there was neither a significant correlation between BMI and PSV (0.16, = 0.745) nor a significant correlation between testosterone and PSV (0.029, = 0.552). Also, there was no correlation between PSV and both dyslipidaemia and penile PD.
CONCLUSIONS
Ageing, tobacco consumption, DM and hypertension seem to have a negative impact on penile haemodynamics, which was statistically significant. In our patients, there was no statistically significant effect on penile haemodynamics in patients with increased BMI, low testosterone or PD or according to the size of the penis.
PubMed: 38179020
DOI: 10.1002/bco2.275 -
Academic Radiology Mar 2024This study aimed to investigate the value of multiplexed sensitivity encoding with reversed polarity gradients in improving the quality of diffusion-weighted imaging...
Improved Value of Multiplexed Sensitivity Encoding DWI with Reversed Polarity Gradients in Diagnosing Prostate Cancer: A Comparison Study with Single-Shot DWI and MUSE DWI.
RATIONALE AND OBJECTIVES
This study aimed to investigate the value of multiplexed sensitivity encoding with reversed polarity gradients in improving the quality of diffusion-weighted imaging (DWI) images of the prostate and the diagnostic efficacy of prostate cancer.
MATERIALS AND METHODS
Seventy-three patients with prostate disease underwent multiplexed sensitivity encoding with reversed polarity gradients (RPG-MUSE), multiplexed sensitivity encoding (MUSE), and single-shot echo-planar imaging (ssEPI) DWI. Three radiologists performed a qualitative image analysis of the three DWI sequences. Qualitative image analysis included artifact minimization, anatomical detail, and sharpness of prostate edges. Two radiologists measured the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), geometric distortion rate, and the apparent diffusion coefficient (ADC) values of the prostate disease tissue. Two radiologists jointly performed Prostate Imaging Reporting and Data System scoring of prostate lesions and compared the diagnostic efficacy of the three DWI sequences for prostate cancer.
RESULTS
There was good agreement among radiologists in the evaluation and measurement of the three DWI sequence images (intraclass correlation coefficient >0.75, P < 0.05). The RPG-MUSE DWI images were rated higher than those of MUSE and ssEPI in terms of artifact minimization, anatomical details, and sharpness of prostate edges (P < 0.05). The SNR and CNR of the RPG-MUSE DWI images were higher than those of MUSE and ssEPI (P < 0.05), and the geometric distortion rate was lower than that of the other two sequences (P < 0.05). There were no statistical differences in ADC values between the three DWI sequences (P > 0.05). The diagnostic efficacy of RPG-MUSE and MUSE DWI was higher than that of ssEPI (P < 0.017).
CONCLUSION
RPG-MUSE can reduce the artifacts and geometric distortion in DWI images of the prostate, improve the SNR and CNR of the images, improve the clarity of anatomical details and boundaries without affecting the measurement of ADC values, has the potential to improve the diagnostic efficacy of prostate lesions, and facilitates the clear display and accurate assessment of prostate lesions.
Topics: Male; Humans; Alprostadil; Diffusion Magnetic Resonance Imaging; Prostatic Neoplasms; Prostate; Echo-Planar Imaging; Reproducibility of Results
PubMed: 37778902
DOI: 10.1016/j.acra.2023.08.027 -
International Journal of Molecular... Dec 2023Although several (chemotherapeutic) protocols to treat acute myeloid leukemia (AML) are available, high rates of relapses in successfully treated patients occur....
Granulocyte-Macrophage-Colony-Stimulating-Factor Combined with Prostaglandin E1 Create Dendritic Cells of Leukemic Origin from AML Patients' Whole Blood and Whole Bone Marrow That Mediate Antileukemic Processes after Mixed Lymphocyte Culture.
Although several (chemotherapeutic) protocols to treat acute myeloid leukemia (AML) are available, high rates of relapses in successfully treated patients occur. Strategies to stabilize remissions are greatly needed. The combination of the (clinically approved) immune-modulatory compounds Granulocyte-Macrophage-Colony-Stimulating-Factor (GM-CSF) and Prostaglandine E1 (PGE-1) (Kit-M) converts myeloid blasts into dendritic cells of leukemic origin (DC). After stimulation with DC ex vivo, leukemia-specific antileukemic immune cells are activated. Therefore, Kit-M treatment may be an attractive immunotherapeutic tool to treat patients with myeloid leukemia. Kit-M-mediated antileukemic effects on whole bone marrow (WBM) were evaluated and compared to whole blood (WB) to evaluate the potential effects of Kit-M on both compartments. WB and WBM samples from 17 AML patients at first diagnosis, in persisting disease and at relapse after allogeneic stem cell transplantation (SCT) were treated in parallel with Kit-M to generate DC/DC. Untreated samples served as controls. After a mixed lymphocyte culture enriched with patients' T cells (MLC), the leukemia-specific antileukemic effects were assessed through the degranulation- (CD107a T cells), the intracellular IFNγ production- and the cytotoxicity fluorolysis assay. Quantification of cell subtypes was performed via flow cytometry. In both WB and WBM significantly higher frequencies of (mature) DC were generated without induction of blast proliferation in Kit-M-treated samples compared to control. After MLC with Kit-M-treated vs. not pretreated WB or WBM, frequencies of (leukemia-specific) immunoreactive cells (e.g., non-naive, effector-, memory-, CD3β7 T cells, NK- cells) were (significantly) increased, whereas leukemia-specific regulatory T cells (T, CD152 T cells) were (significantly) decreased. The cytotoxicity fluorolysis assay showed a significantly improved blast lysis in Kit-M-treated WB and WBM compared to control. A parallel comparison of WB and WBM samples revealed no significant differences in frequencies of DC, (leukemia-specific) immunoreactive cells and achieved antileukemic processes. Kit-M was shown to have comparable effects on WB and WBM samples regarding the generation of DC and activation of (antileukemic) immune cells after MLC. This was true for samples before or after SCT. In summary, a potential Kit-M in vivo treatment could lead to antileukemic effects in WB as well as WBM in vivo and to stabilization of the disease or remission in patients before or after SCT. A clinical trial is currently being planned.
Topics: Humans; Alprostadil; Granulocyte-Macrophage Colony-Stimulating Factor; Dendritic Cells; Bone Marrow; Lymphocyte Activation; Leukemia, Myeloid, Acute; T-Lymphocytes, Regulatory; Granulocytes; Macrophages
PubMed: 38139264
DOI: 10.3390/ijms242417436 -
Cellular and Molecular Life Sciences :... Jan 2024In embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), the expression of an RNA-binding pluripotency-relevant protein, LIN28, and the absence of its...
In embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), the expression of an RNA-binding pluripotency-relevant protein, LIN28, and the absence of its antagonist, the tumor-suppressor microRNA (miRNA) let-7, play a key role in maintaining pluripotency. Muse cells are non-tumorigenic pluripotent-like stem cells residing in the bone marrow, peripheral blood, and organ connective tissues as pluripotent surface marker SSEA-3(+). They express pluripotency genes, differentiate into triploblastic-lineage cells, and self-renew at the single cell level. Muse cells do not express LIN28 but do express let-7 at higher levels than in iPSCs. In Muse cells, we demonstrated that let-7 inhibited the PI3K-AKT pathway, leading to sustainable expression of the key pluripotency regulator KLF4 as well as its downstream genes, POU5F1, SOX2, and NANOG. Let-7 also suppressed proliferation and glycolysis by inhibiting the PI3K-AKT pathway, suggesting its involvement in non-tumorigenicity. Furthermore, the MEK/ERK pathway is not controlled by let-7 and may have a pivotal role in maintaining self-renewal and suppression of senescence. The system found in Muse cells, in which the tumor suppressor let-7, but not LIN28, tunes the expression of pluripotency genes, might be a rational cell system conferring both pluripotency-like properties and a low risk for tumorigenicity.
Topics: Alprostadil; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Embryonic Stem Cells; Gene Expression
PubMed: 38261036
DOI: 10.1007/s00018-023-05089-9 -
International Journal of Molecular... Sep 2023Multilineage-differentiating stress-enduring (Muse) cells are newly established pluripotent stem cells. The aim of the present study was to examine the potential of the...
Multilineage-differentiating stress-enduring (Muse) cells are newly established pluripotent stem cells. The aim of the present study was to examine the potential of the systemic administration of Muse cells as an effective treatment for subacute SCI. We intravenously administered the clinical product "CL2020" containing Muse cells to a rat model two weeks after mid-thoracic spinal cord contusion. Eight experimental animals received CL2020, and twelve received the vehicle. Behavioral analyses were conducted over 20 weeks. Histological evaluations were performed. After 20 weeks of observation, diphtheria toxin was administered to three CL2020-treated animals to selectively ablate human cell functions. Hindlimb motor functions significantly improved from 6 to 20 weeks after the administration of CL2020. The cystic cavity was smaller in the CL2020 group. Furthermore, larger numbers of descending 5-HT fibers were preserved in the distal spinal cord. Muse cells in CL2020 were considered to have differentiated into neuronal and neural cells in the injured spinal cord. Neuronal and neural cells were identified in the gray and white matter, respectively. Importantly, these effects were reversed by the selective ablation of human cells by diphtheria toxin. Intravenously administered Muse cells facilitated the therapeutic potential of CL2020 for severe subacute spinal cord injury.
Topics: Rats; Humans; Animals; Alprostadil; Diphtheria Toxin; Spinal Cord Injuries; Cell Differentiation; Spinal Cord; Administration, Intravenous
PubMed: 37834052
DOI: 10.3390/ijms241914603 -
Nagoya Journal of Medical Science Feb 2024Prostaglandin E1 intracavernous injection test is an established method for diagnosing erectile dysfunction. However, the evaluation is non-objective and often...
Prostaglandin E1 intracavernous injection test is an established method for diagnosing erectile dysfunction. However, the evaluation is non-objective and often influenced by the evaluator's subjectivity. Herein, we measured and objectively evaluated shear wave elastography results of the corpus cavernosum before and after injection in 16 patients who underwent prostaglandin E1 testing. The response score of prostaglandin E1 tests were "1" in 2 cases, "2" in 2 cases, and "3" in 12 cases. The average transmission velocity before the injection and at the time of maximum erection after the injection were 2.21 m/s and 1.57 m/s, respectively. Transmission velocity decreased during erection in 14 of 16 cases (87.5%). The overall rate of change in transmission velocity due to injection was -26.7% and was significantly different between the poor (responses 1 and 2: -16.1%) and good erection (response 3: -30.2%) groups. To the best of our knowledge, this is the first attempt to evaluate erectile phenomenon using percutaneous ultrasonic elastography in Japan. Rate of change in shear wave transmission velocity due to prostaglandin E1 injection in the corpus cavernosum penis was associated with the degree of erection. Therefore, the rate of change in shear wave transmission velocity in the corpus cavernosum penis could be used as an objective index of erectile phenomenon. Percutaneous ultrasonic elastography is a non-invasive and useful test method for diagnosing erectile dysfunction, determining the therapeutic effect, and predicting prognosis.
Topics: Male; Humans; Erectile Dysfunction; Alprostadil; Elasticity Imaging Techniques; Penile Erection; Penis
PubMed: 38505715
DOI: 10.18999/nagjms.86.1.104 -
Deutsches Arzteblatt International Nov 2023
Topics: Humans; Cause of Death; Alprostadil; International Classification of Diseases; Death Certificates
PubMed: 38099602
DOI: 10.3238/arztebl.m2023.0190