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  1. AU=Mandel H G
  2. AU="Duffy, Richard"
  3. AU=Kaseb Hatem AU=Kaseb Hatem
  4. AU=Kong Tak?kwan AU=Kong Tak?kwan
  5. AU=Nagaraja Sridevi
  6. AU="Bu, Yingzi"
  7. AU=Seddighi Hamed AU=Seddighi Hamed
  8. AU="De Keyser, Johan"
  9. AU="Zhenqiang Bi"
  10. AU=Wang Jun
  11. AU=Zhang Fuping
  12. AU="Shatilov, D N"

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  1. Artikel ; Online: Intralesional application of medical grade honey improves healing of surgically treated lacerations in horses.

    Mandel, H H / Sutton, G A / Abu, E / Kelmer, G

    Equine veterinary journal

    2019  Band 52, Heft 1, Seite(n) 41–45

    Abstract: Background: Infection and dehiscence of simple lacerations is common in horses, and consistently effective methods of prevention are yet to be found. Honey has been shown to promote wound healing when applied topically; however, intralesional ... ...

    Abstract Background: Infection and dehiscence of simple lacerations is common in horses, and consistently effective methods of prevention are yet to be found. Honey has been shown to promote wound healing when applied topically; however, intralesional application prior to wound closure has not been reported.
    Objectives: To examine whether intralesional application of medical grade honey (MGH) would reduce the incidence of infection and dehiscence following wound closure.
    Study design: Prospective, open-label randomised block design clinical study.
    Methods: Lacerations, treated by field practitioners, were divided into treatment and control groups using block randomisation. Horses in the treatment group received a single intralesional treatment with l-mesitran gel (MGH). Data were collected at the time of wound closure and at suture removal.
    Results: Data from 127 horses were included, 69 MGH-treated and 58 control cases. No adverse effects of the MGH were recorded. MGH-treated horses were more likely to completely heal (P = 0.006, odds ratio [OR] 3.40 95% confidence interval [CI] 1.41-8.20), to have no signs of infection (P = 0.007, OR 3.64, CI 1.42-9.26) and for the veterinarians to report some degree of satisfaction (P = 0.04, OR 2.72, CI 1.05-7.09) compared to control cases. Numbers needed to treat for complete healing was 5.1 (CI 2.8-40).
    Main limitations: Clinical studies have inherent flaws compared to wound healing models, because of variability between wounds. There were more horses with limb injuries in the control group, although not statistically significant, this may have biased the results. Clinical satisfaction and signs of infection were subjective evaluations and evaluators were not blinded to the treatment group.
    Conclusions: Intralesional application of MGH to lacerations prior to wound closure may be beneficial in preventing infection and dehiscence. Larger, blinded studies focusing on wounds at a specific location with more objective assessment should be pursued.
    Mesh-Begriff(e) Animals ; Bacterial Infections/prevention & control ; Bacterial Infections/veterinary ; Female ; Honey ; Horse Diseases/prevention & control ; Horses ; Lacerations/veterinary ; Male ; Wound Healing
    Sprache Englisch
    Erscheinungsdatum 2019-04-15
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Randomized Controlled Trial, Veterinary
    ZDB-ID 41606-x
    ISSN 2042-3306 ; 0425-1644
    ISSN (online) 2042-3306
    ISSN 0425-1644
    DOI 10.1111/evj.13111
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel: Intralesional application of medical grade honey improves healing of surgically treated lacerations in horses

    Mandel, H. H / Sutton, G. A / Abu, E / Kelmer, G

    Equine veterinary journal. 2020 Jan., v. 52, no. 1

    2020  

    Abstract: BACKGROUND: Infection and dehiscence of simple lacerations is common in horses, and consistently effective methods of prevention are yet to be found. Honey has been shown to promote wound healing when applied topically; however, intralesional application ...

    Abstract BACKGROUND: Infection and dehiscence of simple lacerations is common in horses, and consistently effective methods of prevention are yet to be found. Honey has been shown to promote wound healing when applied topically; however, intralesional application prior to wound closure has not been reported. OBJECTIVES: To examine whether intralesional application of medical grade honey (MGH) would reduce the incidence of infection and dehiscence following wound closure. STUDY DESIGN: Prospective, open‐label randomised block design clinical study. METHODS: Lacerations, treated by field practitioners, were divided into treatment and control groups using block randomisation. Horses in the treatment group received a single intralesional treatment with l‐mesitran gel (MGH). Data were collected at the time of wound closure and at suture removal. RESULTS: Data from 127 horses were included, 69 MGH‐treated and 58 control cases. No adverse effects of the MGH were recorded. MGH‐treated horses were more likely to completely heal (P = 0.006, odds ratio [OR] 3.40 95% confidence interval [CI] 1.41–8.20), to have no signs of infection (P = 0.007, OR 3.64, CI 1.42–9.26) and for the veterinarians to report some degree of satisfaction (P = 0.04, OR 2.72, CI 1.05–7.09) compared to control cases. Numbers needed to treat for complete healing was 5.1 (CI 2.8–40). MAIN LIMITATIONS: Clinical studies have inherent flaws compared to wound healing models, because of variability between wounds. There were more horses with limb injuries in the control group, although not statistically significant, this may have biased the results. Clinical satisfaction and signs of infection were subjective evaluations and evaluators were not blinded to the treatment group. CONCLUSIONS: Intralesional application of MGH to lacerations prior to wound closure may be beneficial in preventing infection and dehiscence. Larger, blinded studies focusing on wounds at a specific location with more objective assessment should be pursued.
    Schlagwörter adverse effects ; clinical trials ; confidence interval ; dehiscence ; gels ; honey ; horses ; lacerations ; models ; odds ratio ; tissue repair ; veterinarians
    Sprache Englisch
    Erscheinungsverlauf 2020-01
    Umfang p. 41-45.
    Erscheinungsort John Wiley & Sons, Ltd
    Dokumenttyp Artikel
    Anmerkung JOURNAL ARTICLE
    ZDB-ID 41606-x
    ISSN 0425-1644
    ISSN 0425-1644
    DOI 10.1111/evj.13111
    Datenquelle NAL Katalog (AGRICOLA)

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  3. Artikel ; Online: Oxytocin and orexin systems bidirectionally regulate the ability of opioid cues to bias reward seeking.

    Giannotti, Giuseppe / Mottarlini, Francesca / Heinsbroek, Jasper A / Mandel, Mitchel R / James, Morgan H / Peters, Jamie

    Translational psychiatry

    2022  Band 12, Heft 1, Seite(n) 432

    Abstract: As opioid-related fatalities continue to rise, the need for novel opioid use disorder (OUD) treatments could not be more urgent. Two separate hypothalamic neuropeptide systems have shown promise in preclinical OUD models. The oxytocin system, originating ...

    Abstract As opioid-related fatalities continue to rise, the need for novel opioid use disorder (OUD) treatments could not be more urgent. Two separate hypothalamic neuropeptide systems have shown promise in preclinical OUD models. The oxytocin system, originating in the paraventricular nucleus (PVN), may protect against OUD severity. By contrast, the orexin system, originating in the lateral hypothalamus (LH), may exacerbate OUD severity. Thus, activating the oxytocin system or inhibiting the orexin system are potential therapeutic strategies. The specific role of these systems with regard to specific OUD outcomes, however, is not fully understood. Here, we probed the therapeutic efficacy of pharmacological interventions targeting the orexin or oxytocin system on two distinct metrics of OUD severity in rats-heroin choice (versus choice for natural reward, i.e., food) and cued reward seeking. Using a preclinical model that generates approximately equal choice between heroin and food reward, we examined the impact of exogenously administered oxytocin, an oxytocin receptor antagonist (L-368,899), and a dual orexin receptor antagonist (DORA-12) on opioid choice. Whereas these agents did not alter heroin choice when rewards (heroin and food) were available, oxytocin and DORA-12 each significantly reduced heroin seeking in the presence of competing reward cues when no rewards were available. In addition, the number of LH orexin neurons and PVN oxytocin neurons correlated with specific behavioral economic variables indicative of heroin versus food motivation. These data identify a novel bidirectional role of the oxytocin and orexin systems in the ability of opioid-related cues to bias reward seeking.
    Mesh-Begriff(e) Analgesics, Opioid ; Animals ; Cues ; Heroin ; Intracellular Signaling Peptides and Proteins ; Neuropeptides ; Orexin Receptor Antagonists/pharmacology ; Orexins ; Oxytocin/pharmacology ; Rats ; Receptors, Oxytocin
    Chemische Substanzen Analgesics, Opioid ; Intracellular Signaling Peptides and Proteins ; Neuropeptides ; Orexin Receptor Antagonists ; Orexins ; Receptors, Oxytocin ; Oxytocin (50-56-6) ; Heroin (70D95007SX)
    Sprache Englisch
    Erscheinungsdatum 2022-10-04
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2609311-X
    ISSN 2158-3188 ; 2158-3188
    ISSN (online) 2158-3188
    ISSN 2158-3188
    DOI 10.1038/s41398-022-02161-z
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Pathogenic CANVAS (AAGGG)n repeats stall DNA replication due to the formation of alternative DNA structures.

    Hisey, Julia A / Radchenko, Elina A / Mandel, Nicholas H / McGinty, Ryan J / Matos-Rodrigues, Gabriel / Rastokina, Anastasia / Masnovo, Chiara / Ceschi, Silvia / Hernandez, Alfredo / Nussenzweig, André / Mirkin, Sergei M

    Nucleic acids research

    2024  Band 52, Heft 8, Seite(n) 4361–4374

    Abstract: ... in vitro reveals triplex H-DNA formation by only the pathogenic repeat. Consistently, bioinformatic ... analysis of S1-END-seq data from human cell lines shows preferential H-DNA formation genome-wide by (A2G3)n ...

    Abstract CANVAS is a recently characterized repeat expansion disease, most commonly caused by homozygous expansions of an intronic (A2G3)n repeat in the RFC1 gene. There are a multitude of repeat motifs found in the human population at this locus, some of which are pathogenic and others benign. In this study, we conducted structure-functional analyses of the pathogenic (A2G3)n and nonpathogenic (A4G)n repeats. We found that the pathogenic, but not the nonpathogenic, repeat presents a potent, orientation-dependent impediment to DNA polymerization in vitro. The pattern of the polymerization blockage is consistent with triplex or quadruplex formation in the presence of magnesium or potassium ions, respectively. Chemical probing of both repeats in vitro reveals triplex H-DNA formation by only the pathogenic repeat. Consistently, bioinformatic analysis of S1-END-seq data from human cell lines shows preferential H-DNA formation genome-wide by (A2G3)n motifs over (A4G)n motifs. Finally, the pathogenic, but not the nonpathogenic, repeat stalls replication fork progression in yeast and human cells. We hypothesize that the CANVAS-causing (A2G3)n repeat represents a challenge to genome stability by folding into alternative DNA structures that stall DNA replication.
    Mesh-Begriff(e) Humans ; DNA Replication/genetics ; DNA/metabolism ; DNA/chemistry ; DNA/genetics ; Nucleic Acid Conformation ; DNA Repeat Expansion/genetics ; Replication Protein C/genetics ; Replication Protein C/metabolism
    Chemische Substanzen DNA (9007-49-2) ; RFC1 protein, human ; Replication Protein C (EC 3.6.4.-) ; triplex DNA
    Sprache Englisch
    Erscheinungsdatum 2024-02-21
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkae124
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Abortion Surveillance - United States, 2019.

    Kortsmit, Katherine / Mandel, Michele G / Reeves, Jennifer A / Clark, Elizabeth / Pagano, H Pamela / Nguyen, Antoinette / Petersen, Emily E / Whiteman, Maura K

    Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002)

    2021  Band 70, Heft 9, Seite(n) 1–29

    Abstract: Problem/condition: CDC conducts abortion surveillance to document the number and characteristics of women obtaining legal induced abortions and number of abortion-related deaths in the United States.: Period covered: 2019.: Description of system: ... ...

    Abstract Problem/condition: CDC conducts abortion surveillance to document the number and characteristics of women obtaining legal induced abortions and number of abortion-related deaths in the United States.
    Period covered: 2019.
    Description of system: Each year, CDC requests abortion data from the central health agencies for 50 states, the District of Columbia, and New York City. For 2019, 49 reporting areas voluntarily provided aggregate abortion data to CDC. Of these, 48 reporting areas provided data each year during 2010-2019. Census and natality data were used to calculate abortion rates (number of abortions per 1,000 women aged 15-44 years) and ratios (number of abortions per 1,000 live births), respectively. Abortion-related deaths from 2018 were assessed as part of CDC's Pregnancy Mortality Surveillance System (PMSS).
    Results: A total of 629,898 abortions for 2019 were reported to CDC from 49 reporting areas. Among 48 reporting areas with data each year during 2010-2019, in 2019, a total of 625,346 abortions were reported, the abortion rate was 11.4 abortions per 1,000 women aged 15-44 years, and the abortion ratio was 195 abortions per 1,000 live births. From 2018 to 2019, the total number of abortions increased 2% (from 614,820 total abortions), the abortion rate increased 0.9% (from 11.3 abortions per 1,000 women aged 15-44 years), and the abortion ratio increased 3% (from 189 abortions per 1,000 live births). From 2010 to 2019, the total number of reported abortions, abortion rate, and abortion ratio decreased 18% (from 762,755), 21% (from 14.4 abortions per 1,000 women aged 15-44 years), and 13% (from 225 abortions per 1,000 live births), respectively. In 2019, women in their 20s accounted for more than half of abortions (56.9%). Women aged 20-24 and 25-29 years accounted for the highest percentages of abortions (27.6% and 29.3%, respectively) and had the highest abortion rates (19.0 and 18.6 abortions per 1,000 women aged 20-24 and 25-29 years, respectively). By contrast, adolescents aged <15 years and women aged ≥40 years accounted for the lowest percentages of abortions (0.2% and 3.7%, respectively) and had the lowest abortion rates (0.4 and 2.7 abortions per 1,000 women aged <15 and ≥40 years, respectively). However, abortion ratios in 2019 were highest among adolescents (aged ≤19 years) and lowest among women aged 25-39 years. Abortion rates decreased from 2010 to 2019 for all women, regardless of age. The decrease in abortion rate was highest among adolescents compared with any other age group. From 2018 to 2019, abortion rates decreased or did not change among women aged ≤24 years; however, the abortion rate increased among those aged ≥25 years. Abortion ratios also decreased or did not change from 2010 to 2019 for all age groups, except adolescents aged <15 years. The decrease in abortion ratio was highest among women aged ≥40 years compared with any other age group. From 2018 to 2019, abortion ratios increased for all age groups, except adolescents aged <15 years. In 2019, 79.3% of abortions were performed at ≤9 weeks' gestation, and nearly all (92.7%) were performed at ≤13 weeks' gestation. During 2010-2019, the percentage of abortions performed at >13 weeks' gestation remained consistently low (≤9.0%). In 2019, the highest proportion of abortions were performed by surgical abortion at ≤13 weeks' gestation (49.0%), followed by early medical abortion at ≤9 weeks' gestation (42.3%), surgical abortion at >13 weeks' gestation (7.2%), and medical abortion at >9 weeks' gestation (1.4%); all other methods were uncommon (<0.1%). Among those that were eligible (≤9 weeks' gestation), 53.7% of abortions were early medical abortions. In 2018, the most recent year for which PMSS data were reviewed for pregnancy-related deaths, two women died as a result of complications from legal induced abortion.
    Interpretation: Among the 48 areas that reported data continuously during 2010-2019, overall decreases were observed during 2010-2019 in the total number, rate, and ratio of reported abortions; however, from 2018 to 2019, 1%-3% increases were observed across all measures.
    Public health action: Abortion surveillance can be used to help evaluate programs aimed at promoting equitable access to patient-centered quality contraceptive services in the United States to reduce unintended pregnancies.
    Mesh-Begriff(e) Abortion, Legal/statistics & numerical data ; Adolescent ; Adult ; Centers for Disease Control and Prevention, U.S. ; Female ; Humans ; Population Surveillance ; Pregnancy ; United States/epidemiology ; Young Adult
    Sprache Englisch
    Erscheinungsdatum 2021-11-26
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 605652-0
    ISSN 1545-8636 ; 0892-3787
    ISSN (online) 1545-8636
    ISSN 0892-3787
    DOI 10.15585/mmwr.ss7009a1
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Evaluating interhemispheric connectivity during midline object recognition using EEG.

    Das, Anwesha / Mandel, Alexandra / Shitara, Hitoshi / Popa, Traian / Horovitz, Silvina G / Hallett, Mark / Thirugnanasambandam, Nivethida

    PloS one

    2022  Band 17, Heft 8, Seite(n) e0270949

    Abstract: Functional integration between two hemispheres is crucial for perceptual binding to occur when visual stimuli are presented in the midline of the visual field. Mima and colleagues (2001) showed using EEG that midline object recognition was associated ... ...

    Abstract Functional integration between two hemispheres is crucial for perceptual binding to occur when visual stimuli are presented in the midline of the visual field. Mima and colleagues (2001) showed using EEG that midline object recognition was associated with task-related decrease in alpha band power (alpha desynchronisation) and a transient increase in interhemispheric coherence. Our objective in the current study was to replicate the results of Mima et al. and to further evaluate interhemispheric effective connectivity during midline object recognition in source space. We recruited 11 healthy adult volunteers and recorded EEG from 64 channels while they performed a midline object recognition task. Task-related power and coherence were estimated in sensor and source spaces. Further, effective connectivity was evaluated using Granger causality. While we were able to replicate the alpha desynchronisation associated with midline object recognition, we could not replicate the coherence results of Mima et al. The data-driven approach that we employed in our study localised the source of alpha desynchronisation over the left occipito-temporal region. In the alpha band, we further observed significant increase in imaginary part of coherency between bilateral occipito-temporal regions during object recognition. Finally, Granger causality analysis between the left and right occipito-temporal regions provided an insight that even though there is bidirectional interaction, the left occipito-temporal region may be crucial for integrating the information necessary for object recognition. The significance of the current study lies in using high-density EEG and applying more appropriate and robust measures of connectivity as well as statistical analysis to validate and enhance our current knowledge on the neural basis of midline object recognition.
    Mesh-Begriff(e) Adult ; Brain Mapping ; Electroencephalography ; Humans ; Temporal Lobe ; Visual Perception
    Sprache Englisch
    Erscheinungsdatum 2022-08-26
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0270949
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: Acute hemodialysis therapy in neonates with inborn errors of metabolism.

    Eisenstein, Israel / Pollack, Shirley / Hadash, Amir / Eytan, Danny / Attias, Ori / Halberthal, Michael / Ben-Ari, Josef / Bar-Joseph, Gad / Zelikovic, Israel / Mandel, Hanna / Tal, Galit / Magen, Daniella

    Pediatric nephrology (Berlin, Germany)

    2022  Band 37, Heft 11, Seite(n) 2725–2732

    Abstract: ... presented with IEM-induced neurologic deterioration at 48 h to 14 days post-delivery, and were managed ... at presentation were 5 (3-8) days and 2830 (2725-3115) g, respectively. Two consecutive HD sessions decreased ...

    Abstract Background: Inborn errors of metabolism (IEM), including organic acidemias and urea cycle defects, are characterized by systemic accumulation of toxic metabolites with deleterious effect on the developing brain. While hemodialysis (HD) is most efficient in clearing IEM-induced metabolic toxins, data regarding its use during the neonatal period is scarce.
    Methods: We retrospectively summarize our experience with HD in 20 neonates with IEM-induced metabolic intoxication (seven with maple syrup urine disease, 13 with primary hyperammonia), over a 16-year period, between 2004 and 2020. All patients presented with IEM-induced neurologic deterioration at 48 h to 14 days post-delivery, and were managed with HD in a pediatric intensive care setting. HD was performed through an internal jugular acute double-lumen catheter (6.5-7.0 French), using an AK-200S (Gambro, Sweden) dialysis machine and tubing, with F3 or FXpaed (Fresenius, Germany) dialyzers.
    Results: Median (interquartile range) age and weight at presentation were 5 (3-8) days and 2830 (2725-3115) g, respectively. Two consecutive HD sessions decreased the mean leucine levels from 2281 ± 631 to 179 ± 91 μmol/L (92.1% reduction) in MSUD patients, and the mean ammonia levels from 955 ± 444 to 129 ± 55 μmol/L (86.5% reduction), in patients with hyperammonemia. HD was uneventful in all patients, and led to marked clinical improvement in 17 patients (85%). Three patients (15%) died during the neonatal period, and four died during long-term follow-up.
    Conclusions: Taken together, our results indicate that HD is safe, effective, and life-saving for most neonates with severe IEM-induced metabolic intoxication, when promptly performed by an experienced and multidisciplinary team. A higher resolution version of the Graphical abstract is available as Supplementary information.
    Mesh-Begriff(e) Ammonia ; Child ; Humans ; Infant, Newborn ; Leucine ; Metabolism, Inborn Errors/complications ; Metabolism, Inborn Errors/therapy ; Renal Dialysis/adverse effects ; Renal Dialysis/methods ; Retrospective Studies ; Urea
    Chemische Substanzen Ammonia (7664-41-7) ; Urea (8W8T17847W) ; Leucine (GMW67QNF9C)
    Sprache Englisch
    Erscheinungsdatum 2022-03-03
    Erscheinungsland Germany
    Dokumenttyp Journal Article
    ZDB-ID 631932-4
    ISSN 1432-198X ; 0931-041X
    ISSN (online) 1432-198X
    ISSN 0931-041X
    DOI 10.1007/s00467-022-05507-3
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel ; Online: Trial Participation is Not Associated with Better Biochemical Recurrence-free Survival in a Large Cohort of External Beam Radiotherapy-Treated Intermediate- and High-Risk Prostate Cancer Patients.

    Flammia, R S / Lavigne, D / Tian, Z / Saad, F / Anceschi, U / Gallucci, M / Leonardo, C / Preisser, F / Mandel, P / Chun, F K H / Karakiewicz, P I / Delouya, G / Taussky, D / Hoeh, B

    Clinical oncology (Royal College of Radiologists (Great Britain))

    2022  Band 35, Heft 1, Seite(n) e77–e84

    Abstract: Aims: There is a widespread belief that outcomes of cancer patients treated within clinical trials might not be representative of the outcomes obtained within standard clinical settings. We sought to investigate the effect of trial participation on ... ...

    Abstract Aims: There is a widespread belief that outcomes of cancer patients treated within clinical trials might not be representative of the outcomes obtained within standard clinical settings. We sought to investigate the effect of trial participation on biochemical recurrence (BCR) in localised, D'Amico intermediate- and high-risk prostate cancer patients treated with external beam radiotherapy (EBRT).
    Materials and methods: We relied on a study population treated with EBRT between January 2001 and January 2021 at a single tertiary care centre, stratified according to trial enrolment. Separate Kaplan-Meier and multivariable Cox regression models tested BCR-free survival at 60 months within intermediate- and high-risk EBRT patients, after adjustment for covariables. Additionally, the analyses were refitted after inverse probability treatment weighting was performed separately for both risk subgroups.
    Results: Of 932 eligible patients, 635 (68%) and 297 (32%) had intermediate- and high-risk prostate cancer, respectively. Overall, 53% of patients were trial participants. BCR rates were 11 versus 5% (P = 0.27) and 12 versus 14% (P = 0.08) in trial participants versus non-participants for intermediate- and high-risk subgroups, respectively. Differences in patient and clinical characteristics were recorded. Trial participation status failed to reach predictor status in multivariable Cox regression models for BCR in both intermediate-risk (hazard ratio 1.34; 95% confidence interval 0.71-2.49; P = 0.4) and high-risk patients (hazard ratio 1.03; 95% confidence interval 0.45-2.34; P = 0.9). Virtually the same results were recorded in inverse probability treatment weighting cohorts.
    Conclusions: Relying on a large cohort of EBRT-treated intermediate- and high-risk patients, no BCR differences were recorded between trial participants and non-participants after accounting for confounders.
    Mesh-Begriff(e) Humans ; Male ; Brachytherapy/methods ; Proportional Hazards Models ; Prostate-Specific Antigen ; Prostatectomy ; Prostatic Neoplasms/surgery ; Clinical Trials as Topic
    Chemische Substanzen Prostate-Specific Antigen (EC 3.4.21.77)
    Sprache Englisch
    Erscheinungsdatum 2022-09-14
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 1036844-9
    ISSN 1433-2981 ; 0936-6555
    ISSN (online) 1433-2981
    ISSN 0936-6555
    DOI 10.1016/j.clon.2022.08.031
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel: Transcriptomic Maps of Colorectal Liver Metastasis: Machine Learning of Gene Activation Patterns and Epigenetic Trajectories in Support of Precision Medicine.

    Ashekyan, Ohanes / Shahbazyan, Nerses / Bareghamyan, Yeva / Kudryavzeva, Anna / Mandel, Daria / Schmidt, Maria / Loeffler-Wirth, Henry / Uduman, Mohamed / Chand, Dhan / Underwood, Dennis / Armen, Garo / Arakelyan, Arsen / Nersisyan, Lilit / Binder, Hans

    Cancers

    2023  Band 15, Heft 15

    Abstract: The molecular mechanisms of the liver metastasis of colorectal cancer (CRLM) remain poorly understood. Here, we applied machine learning and bioinformatics trajectory inference to analyze a gene expression dataset of CRLM. We studied the co-regulation ... ...

    Abstract The molecular mechanisms of the liver metastasis of colorectal cancer (CRLM) remain poorly understood. Here, we applied machine learning and bioinformatics trajectory inference to analyze a gene expression dataset of CRLM. We studied the co-regulation patterns at the gene level, the potential paths of tumor development, their functional context, and their prognostic relevance. Our analysis confirmed the subtyping of five liver metastasis subtypes (LMS). We provide gene-marker signatures for each LMS, and a comprehensive functional characterization that considers both the hallmarks of cancer and the tumor microenvironment. The ordering of CRLMs along a pseudotime-tree revealed a continuous shift in expression programs, suggesting a developmental relationship between the subtypes. Notably, trajectory inference and personalized analysis discovered a range of epigenetic states that shape and guide metastasis progression. By constructing prognostic maps that divided the expression landscape into regions associated with favorable and unfavorable prognoses, we derived a prognostic expression score. This was associated with critical processes such as epithelial-mesenchymal transition, treatment resistance, and immune evasion. These factors were associated with responses to neoadjuvant treatment and the formation of an immuno-suppressive, mesenchymal state. Our machine learning-based molecular profiling provides an in-depth characterization of CRLM heterogeneity with possible implications for treatment and personalized diagnostics.
    Sprache Englisch
    Erscheinungsdatum 2023-07-28
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15153835
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel ; Online: Hemodynamical consequences and tolerance of sustained ventricular tachycardia.

    Delasnerie, Hubert / Biendel, Caroline / Elbaz, Meyer / Mandel, Franck / Beneyto, Maxime / Domain, Guillaume / Voglimacci-Stephanopoli, Quentin / Mondoly, Pierre / Delmas, Clement / Bongard, Vanina / Rollin, Anne / Maury, Philippe

    PloS one

    2023  Band 18, Heft 5, Seite(n) e0285802

    Abstract: Aims: Factors underlying clinical tolerance and hemodynamic consequences of monomorphic sustained ventricular tachycardia (VT) need to be clarified.: Methods: Intra-arterial pressures (IAP) during VT were collected in patients admitted for VT ... ...

    Abstract Aims: Factors underlying clinical tolerance and hemodynamic consequences of monomorphic sustained ventricular tachycardia (VT) need to be clarified.
    Methods: Intra-arterial pressures (IAP) during VT were collected in patients admitted for VT ablation and correlated to clinical, ECG and baseline echocardiographical parameters.
    Results: 114 VTs from 58 patients were included (median 67 years old, 81% ischemic heart disease, median left ventricular ejection fraction 30%). 61 VTs were untolerated needing immediate termination (54%). VT tolerance was tightly linked to the evolution of IAPs. Faster VT rates (p<0.0001), presence of resynchronization therapy (p = 0.008), previous anterior myocardial infarction (p = 0.009) and more marginally larger baseline QRS duration (p = 0.1) were independently associated with VT tolerance. Only an inferior myocardial infarction was more often present in patients with only tolerated VTs vs patients with only untolerated VTs in multivariate analysis (OR 3.7, 95% CI 1.4-1000, p = 0.03). In patients with both well-tolerated and untolerated VTs, a higher VT rate was the only variable independently associated with untolerated VT (p = 0.02). Two different patterns of hemodynamic profiles during VT could be observed: a regular 1:1 relationship between electrical (QRS) and mechanical (IAP) events or some dissociation between both. VT with the second pattern were more often untolerated compared to the first pattern (78% vs 29%, p<0.0001).
    Conclusion: This study helps to explain the large variability in clinical tolerance during VT, which is clearly related to IAP. VT tolerance may be linked to resynchronization therapy, VT rate, baseline QRS duration and location of myocardial infarction.
    Mesh-Begriff(e) Humans ; Aged ; Stroke Volume ; Ventricular Function, Left ; Tachycardia, Ventricular ; Myocardial Infarction/complications ; Echocardiography ; Catheter Ablation
    Sprache Englisch
    Erscheinungsdatum 2023-05-17
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0285802
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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