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Conflict of interest
The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest.
PMC9531217
Ethical approval
Eligible participants (tertiary students) received detailed written information about the study and then provided their informed consent during each assessment session. To maintain the participants’ confidentiality, the research team de-identified and securely stored the collected data. This study has ethical approval ...
PMC9531217
Consent to participate
EVENTS
Prior to study, all participants had provided their consent to take part in the study and have their de-identified data published, presented in public events and conferences.
PMC9531217
Consent for publication
EVENTS
Prior to study, all participants had provided their consent to have their de-identified data published, presented in public events and conferences.
PMC9531217
References
PMC9531217
Background
tendinopathies, tendinopathy
DEGENERATIVE
The etiology of tendinopathy remains controversial and it is unknown whether degenerative structural changes in tendinopathies are reversible.
PMC10634075
Hypothesis
gluteal tendinopathy
There will be no structural change on magnetic resonance imaging (MRI) taken > 2-years after treatment for gluteal tendinopathy.
PMC10634075
Study Design
Extension of a single site, double-blind, prospective randomized-controlled trial to analyze the additional outcome measure; MRI changes.
PMC10634075
Methods
gluteal tendinopathy
University of Melbourne ethics approval number: 1852900, trial registration: ACTRN12613000677707. Participants with gluteal tendinopathy who had previously received a leukocyte-rich platelet-rich plasma injection (LR-PRP) or a corticosteroid injection (CSI) had a post treatment MRI between at least 2-years and up to 7 ...
PMC10634075
Results
Participants (n = 20) underwent MRI at mean time of 4.15 (SD 1.11; range 2–7) years after their initial treatment. There was no change in the overall mean MHIP score for the CSI group (Pre 4.3 (SD 2.3) Post 4.3 (SD 1.1), p = 1.00). Although there was an improvement in the LR-PRP group mean MHIP score (Pre 5.3 (SD 3.0) ...
PMC10634075
Conclusion
tendinopathy, gluteal tendinopathy
The hypothesis that there would be no improvement in MHIP scores following treatment of gluteal tendinopathy was supported. Findings of improvement in the LR-PRP group at 4 years would support further studies powered to look for structural improvement. These findings suggest that structural change following treatment f...
PMC10634075
Clinical relevance
DEGENERATIVE
The study suggests that degenerative structural changes in tendons may be reversible.
PMC10634075
Supplementary Information
The online version contains supplementary material available at 10.1186/s12880-023-01150-y.
PMC10634075
Significance
PMC10634075
Supplementary Information
The online version contains supplementary material available at 10.1186/s12880-023-01150-y.
PMC10634075
Keywords
PMC10634075
Introduction
tendinopathic tendons, gluteal tendinopathy, tendinopathy, musculoskeletal diseases
PATHOPHYSIOLOGY, MUSCULOSKELETAL DISEASES
Accounting for up to 30% of all musculoskeletal consultations [Whilst tendinopathy was originally considered an ‘inflammatory’ condition, the pathophysiology of musculoskeletal diseases is being re-considered.Recent molecular evidence, has acknowledged the inflammatory nature of tendinopathy with key inflammatory proce...
PMC10634075
Methods
PMC10634075
Ethics approval
The study was conducted in accordance with the Declaration of Helsinki and Ethics approval was obtained from the University of Melbourne Human Research Ethics Committee (Ethics approval number: 1852900). The trial was registered with ACTRN12613000677707. All participants provided written informed consent to participate...
PMC10634075
Study design
This study is an extension of a single site (Melbourne), double-blind, prospective RCT to analyze the structural outcome measure of MRI changes at 2-years or more post treatment in addition to the previously reported clinical outcomes measures [
PMC10634075
Participants
gluteal tendinopathy
Participants were drawn from the existing RCT comparing LR-PRP to corticosteroid injection (CSI) for gluteal tendinopathy [
PMC10634075
Intervention
No treatment was given to the participants in this study although participants had previously received a single LR-PRP injection (group 1), a single CSI (group 2) or a single CSI followed by a LR-PRP injection (group 3) as described by the methodology and protocol of Fitzpatrick et al. [Where possible, scans were taken...
PMC10634075
Outcome measure
bursitis, tendinopathy, fatty infiltration
BONE MARROW OEDEMA, BURSITIS, PATHOLOGY, FATTY INFILTRATION
A blinded, senior musculoskeletal radiologist graded all de-identified MRI scans using the Melbourne Hip Score (MHIP). The severity of soft tissue bursitis and direct gluteal tendon pathology has been shown to affect the adjacent structures, notably fatty infiltration of muscle and bone marrow oedema. Thus, the MHIP sc...
PMC10634075
Statistical analysis
Analysis was conducted using STATA version 13.1 (Stata Corp. 2016 Stata Statistical Software: Release 13.1. College station, TX: Stata Corp LP). Classical 2-sided paired student t-tests were performed to determine if there was a statistically significant difference in the change in pre-and post-treatment score within t...
PMC10634075
Results
PMC10634075
Flow of patients
Demographic dataY
Of 76 participants who were eligible for this study, 36 were excluded as they did not have available baseline MRI scans and 8 did not consent to participate (Fig.  MHIP scores graphical representation. MHIP, Melbourne Hip MRI Score; LR-PRP, leukocyte-rich platelet-rich plasma; CSI, corticosteroid injection Demographic ...
PMC10634075
Time to post-treatment MRI
Participants received post-treatment MRI at a mean time of 4.15 (SD 1.11; range 2–7) years after their initial treatment.
PMC10634075
Change in MHIP score overall
Table There was no change in the overall mean MHIP score for the CSI group (Pre 4.3 (SD 2.3) Post 4.3 (SD 1.2)) but there was an improvement in the LR-PRP group mean MHIP score (Pre 5.3 (SD 3.0) Post 4.8 (SD 2.5), p = 0.56) (supplementary tables S1 and S2).Figure  MHIP scores by treatment group comparisonMHIP, Melbourn...
PMC10634075
Change in MHIP score elements
TB, bone marrow oedema, gluteal tendinopathy, tendinopathy, fatty muscular atrophy
BONE MARROW OEDEMA, TROCHANTERIC BURSITIS, ATROPHIC
The MHIP score is calculated based on 5 elements although the total score reflects tendinopathy severity : gluteal tendinopathy rating (GT) and trochanteric bursitis (TB), cortical irregularity (CI) and bone marrow oedema (BO) and fatty muscular atrophy (FA) [Tendon related scores were similar between the CSI group and...
PMC10634075
Discussion
tendinopathic achilles tendons, tendinopathy, gluteal tendinopathy
DISEASE PROGRESSION, DISEASE, NEOVASCULARIZATION
Our hypothesis was that there would be no improvement in MHIP MRI scores following treatment for gluteal tendinopathy at 2 years or more post-treatment. Overall, the results confirmed this. However, there was a reduction in the mean MHIP scores in the LR-PRP group from 5.3 (SD 3.0) to 4.77 (SD 2.5), p = 0.56) and in fi...
PMC10634075
Conclusion
tendinopathy, gluteal tendinopathy
The hypothesis that there would be no improvement in MHIP scores following treatment of gluteal tendinopathy was supported. Findings of improvement in the LR-PRP group at 4 years would support further studies powered to look for structural improvement. These findings suggest that structural change following treatment f...
PMC10634075
Acknowledgements
The authors would like to acknowledge Nathan Tso for his assistance in preparation of the data. Thanks also to Richard O’Sullivan for reading and grading MRI scans and Sally Boyd for her outstanding work as clinical trial coordinator.
PMC10634075
Authors’ contributions
J.F. contributed to the study design and both authors were involved in data collection, interpretation and analysis. G.C. wrote the first draft and J.F. made substantial contributions to critically revise subsequent drafts. Both authors gave final approval of the version published. The authors agree to be accountable f...
PMC10634075
Funding
Funding for this project was received from Joint Health Institute Ltd. Australia.
PMC10634075
Data Availability
Data relating to this study has been published as a part of the article and the supplementary material.
PMC10634075
Declarations
PMC10634075
Ethical approval and consent to participate
The study was conducted in accordance with the Declaration of Helsinki and Ethics approval was obtained from the University of Melbourne Human Research Ethics Committee (Ethics approval number: 1852900). The trial was registered with ACTRN12613000677707. All participants provided written informed consent to participate...
PMC10634075
Consent for publication
Not Applicable.
PMC10634075
Competing interests
The authors declare no competing interests.
PMC10634075
References
PMC10634075
Background
hyperphosphatemia
HYPERPHOSPHATEMIA
This study aimed to investigate the effect of a family-centered empowerment program on hyperphosphatemia management.
PMC10476304
Method
hyperphosphatemia, coin toss
HYPERPHOSPHATEMIA
This experimental study was performed on 80 randomly selected eligible patients with hyperphosphatemia undergoing hemodialysis. Patients were assigned randomly to two groups of family-centered empowerment program (FCEPG) and control group (CG) by coin toss (40 people per group). Data collection tools were the researche...
PMC10476304
Results
Inter-group comparisons showed no significant difference between FCEPG and CG in terms of the mean score of knowledge of phosphate control, adherence to dietary restriction of phosphorus intake, adherence to medication, and the mean serum phosphorus level before the empowerment program, but showed significant differenc...
PMC10476304
Conclusion
The findings of this study can be used in various fields of healthcare in the hospital and community.
PMC10476304
Keywords
PMC10476304
Introduction
hyperphosphatemia
END-STAGE RENAL DISEASE, HYPERPHOSPHATEMIA, COMPLICATION
Maintenance hemodialysis is a commonly used treatment for end-stage renal disease. In this condition, phosphate becomes easily retained in the body due to decreased renal function, leading to hyperphosphatemia, a common complication in these patients [Primary interventions for hyperphosphatemia management include the d...
PMC10476304
Literature review
hyperphosphatemia, ’
HYPERPHOSPHATEMIA
The effects of education programs on knowledge, adherence to dietary and medication regimens, and serum phosphorus levels of HPs with hyperphosphatemia have been the subject of several studies. In a study by Yin et al., the results showed an improvement in the HPs’ phosphate control rate, their knowledge of phosphate c...
PMC10476304
Methods
PMC10476304
Study design and setting
This study was experimental research conducted on two groups of HPs: 1- patients participating in an FCEP (hereafter refers to as FCEPG) and 2- patients in the control group (hereafter refers to as CG). All patients were recruited from the hemodialysis ward of Shahid Beheshti Hospital in Hamadan, Iran. This ward has 30...
PMC10476304
Participants and recruitment
death, illness
All participants were HPs. The sample size was computed using the following formula based on the findings of Lim et al. [For sampling, the first researcher identified eligible HPs with the help of nurses. Participants of FCEPG were recruited exclusively from the morning shift and CG from the evening shift to prevent co...
PMC10476304
Outcome measurements
PMC10476304
Primary outcomes
The primary outcomes of the program were assumed to be a change in patients’ knowledge of phosphate control, adherence to DRPI, and adherence to medication, which were measured by the researcher-made Phosphate Control Knowledge Scale, researcher-made Dietary Restriction of Phosphorus Intake Scale (DRPI-S), and the eigh...
PMC10476304
Secondary outcomes
SECONDARY
The secondary outcome of the program was assumed to be a change in serum phosphorus level.
PMC10476304
Baseline
The first researcher collected data. Baseline measurements for FCEPG and CG were performed before interventions while HPs were undergoing hemodialysis. For illiterate HPs, the questions were read aloud and answers were recorded by the first researcher.
PMC10476304
Follow-ups
Follow-up measurements were performed once one month after FCEP (Follow-Up1) and another time three months after FCEP (Follow-Up2) at patients’ subsequent hemodialysis appointments before the start of hemodialysis. CONSORT flow chart of the study is illustrated in Fig. CONSORT flow chart of the study
PMC10476304
Measures
PMC10476304
Sociodemographic and clinical data of participants and family caregivers
primary disease
Sociodemographic and clinical information questionnaire contained 11 questions about HPs (age, gender, education level, marital status, employment status, duration of undergoing hemodialysis, primary disease, dialysis frequency, receiving vitamin D, and calcimimetics, and smoking. This questionnaire also contained seve...
PMC10476304
Knowledge of phosphate control
Knowledge of phosphate control was measured by the Phosphate Control Knowledge Scale, which was a researcher-made tool. This questionnaire was developed by adapting the tools of similar studies and scientific recourses [This tool has 16 items with the answers “true” (1 point), “false” (0 points), and “I don’t know” (0 ...
PMC10476304
Adherence to dietary restriction of phosphorus intake
Adherence to DRPI was measured by the researcher-made Dietary Restriction of Phosphorus Intake Scale (DRPI-S), which was also developed by the researchers based on scientific sources [Dietary restriction of phosphorus intake scaleThe validity and reliability of this tool were established in the same way as described fo...
PMC10476304
Adherence to medication
Adherence to medication was measured using the version of eight-item Morisky Medication Adherence Scale (MMAS-8)
PMC10476304
Serum phosphorus measurement
hyperphosphatemia
HYPERPHOSPHATEMIA
At the dialysis ward, serum phosphorus level measurement was a routine procedure for all HPs with hyperphosphatemia while fasting. This procedure involved a nurse taking a blood sample, sending it to the hospital’s laboratory, and then recording the results in the HP’s medical file at 8 AM. The first researcher (respon...
PMC10476304
Data analysis
The collected data were processed using the software SPSS version 26. The data were analyzed by descriptive statistical methods such as computing numerical measures (mean and standard deviation) and inferential tests. The independent t-test and the chi-square test were used to compare FCEPG and CG in terms of demograph...
PMC10476304
Discussion
hyperphosphatemia, CKD
SECONDARY, HYPERPHOSPHATEMIA, ACUTE CORONARY SYNDROME
The goal of this study was to investigate the effect of an FCEP on hyperphosphatemia management in HPs. The results showed that FCEP could have a positive impact on the patients’ knowledge of phosphate control, adherence to DRPI, and adherence to medication as primary outcomes and on their serum phosphorus levels as th...
PMC10476304
Acknowledgements
We would like to thank managers and patients at Shahid beheshti hospital in Hamedal for their assistance and cooperation.
PMC10476304
Authors’ contributions
Conceptualization and methodology: Parvaneh Vasli, and Noushin Bakhtiari; Formal analysis and investigation: Noushin Bakhtiari, Parvaneh Vasli, and Malihe Nasiri; Writing-original draft: Parvaneh Vasli; Writing– review and editing: Meimanat Hosseini.
PMC10476304
Funding
No funding or sponsorship was received for this study or publication of this article.
PMC10476304
Availability of data and materials
The data used to support the findings of this study are available from the corresponding author upon reasonable request.
PMC10476304
Declarations
PMC10476304
Ethics approval and consent to participate
All the measures taken in this study were approved by the Ethics Committee of Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran (code no. IR.SBMU.PHNM.1400.104) in agreement with the ethical standards of the 1964 Declaration of Helsinki and its later amendments. Informed consent was obtained from all ...
PMC10476304
Consent for publication
Not applicable.
PMC10476304
Competing interests
The authors declare no competing interests.
PMC10476304
References
PMC10476304
Background
tumor
TUMOR, SOLID TUMORS
Indoleamine 2,3-dioxygenase 1 (IDO1), an interferon-inducible enzyme, contributes to tumor immune intolerance. Immune checkpoint inhibition may increase interferon levels; combining IDO1 inhibition with immune checkpoint blockade represents an attractive strategy. Epigenetic agents trigger interferon responses and may ...
PMC10241827
Methods
SOLID TUMORS
ECHO-206 was a Phase I/II study where treatment-experienced patients with advanced solid tumors (
PMC10241827
Results
asthenia, nausea, fatigue, PAD, toxicities
ADVERSE EVENTS, PAD
In Phase I, no dose-limiting toxicities were reported, the MTD was not reached; a PAD was not determined. ORR was 5.7%, with four partial responses. The most common treatment-related adverse events (AEs) were fatigue (42.9%) and nausea (42.9%). Twelve (17.1%) patients experienced ≥1 fatal AE, one of which (asthenia) wa...
PMC10241827
Conclusions
SOLID TUMORS
Although the azacitidine-epacadostat-pembrolizumab regimen was well tolerated, it was not associated with substantial clinical response in patients with advanced solid tumors previously exposed to immunotherapy.
PMC10241827
Subject terms
PMC10241827
Introduction
NSCLC, tumor, T-cell apoptosis, Tumor
TUMOR, CANCER PROGRESSION, TUMOR, PROLIFERATION, DISEASE, NSCLC, IMMUNE TOLERANCE, TUMOR GROWTH
Tumor cells can evade host immune responses by exploiting immune checkpoint pathways [The mechanisms responsible for resistance to immune checkpoint inhibition are not fully defined, but treatment responsiveness has been associated with the presence of an inflamed tumor microenvironment [Immunotherapy strategies target...
PMC10241827
Methods
PMC10241827
Study design and participants
NSCLC, colorectal cancer, tumor, CRC, PAD, Tumors
COLORECTAL CANCER, TUMOR, DISEASE, SOLID TUMORS, TUMORS, PAD, NSCLC
ECHO-206 (NCT02959437) was an international, open-label, Phase I/II study in which patients received an epigenetic priming regimen and an immunotherapy doublet consisting of epacadostat and pembrolizumab. The study was undertaken at 11 centers in the United States, United Kingdom, and Spain. Patients enrolled in Phase ...
PMC10241827
Sample size considerations
toxicities, DLTs
PAD
Part 1 dose escalation used a 3 + 3 + 3 design, and the sample size was determined by the frequency of dose-limiting toxicities (DLTs) and final number of dose levels tested before the MTD or PAD was established.For Part 2 expansion, the sample size was based on the Simon 2-stage design. Based on a one-sided type I err...
PMC10241827
Treatment
This study was originally designed to explore several epigenetic priming regimens, but azacitidine was the one tested due to the early study termination (discussed in the study conduct section).Treatment cycles were 21 days long. Dose escalation began with azacitidine 75 mg, pembrolizumab 200 mg IV Q3W, and oral epacad...
PMC10241827
Study conduct
melanoma
MELANOMA
The study was initiated on February 27, 2017, and a strategic decision was made on April 11, 2018, to permanently stop enrollment. This decision was based on the results of the Phase III ECHO-301/ KEYNOTE-252 study, which compared epacadostat plus pembrolizumab with placebo plus pembrolizumab in patients with advanced ...
PMC10241827
Endpoints
tumor, death, Tumor, TILs, T-cell infiltration, Safety/tolerability
DISEASE PROGRESSION, TUMOR, ADVERSE EVENT, TUMOR, PAD, SECONDARY
In Phase I, the primary endpoints were safety/tolerability and identification of the MTD or PAD. The MTD was defined as the highest dose at which less than one-third of patients (out of a minimum of six patients) experienced a DLT (see Additional file 2: Supplementary Table SIn Phase II, investigator-assessed ORR per R...
PMC10241827
Statistics
T-cell infiltration
The response-evaluable population, which was used for the efficacy analysis, comprised patients who received ≥1 dose of any study drug and completed a baseline scan. Patients in the response-evaluable population also had to have ≥1 post-baseline scan, been on study for ≥70 days, or discontinued study treatment. The saf...
PMC10241827
Results
PMC10241827
Changes in T-cell infiltration
tumor
TUMOR, EVALUABLE
Evaluable samples (defined as tumor content ≥10%) for paired pre- and on-treatment biopsies were available from seven patients who received concurrent administration of azacitidine, epacadostat, and pembrolizumab (dose escalation:
PMC10241827
Discussion
tumor, tumors, melanoma
TUMOR, TUMORS, SOLID TUMORS, MELANOMA
ECHO-206 represents the largest prospective study of combination treatment with an epigenetic modulator (azacitidine) and immunotherapy (epacadostat plus pembrolizumab) performed to date. Although this study established that azacitidine 100 mg could be safely combined with epacadostat and pembrolizumab, this regimen (w...
PMC10241827
Supplementary information
The online version contains supplementary material available at 10.1038/s41416-023-02267-1.
PMC10241827
Acknowledgements
Cancer
CANCER
Dr. Brana wishes to thank the Instituto de Salud Carlos III (Rio Hortega contract CM15/00255); the Comprehensive Program of Cancer Immunotherapy & Immunology (CAIMI), which was supported by the Banco Bilbao Vizcaya Argentaria Foundation (grant 89/2017); the La Caixa Foundation (LCF/PR/CEO7/50610001); and the Cellex Fou...
PMC10241827
Author contributions
JJL: conception and design of the study, acquisition of data, and analysis and interpretation of data. MF: acquisition of data and analysis and interpretation of data. CS: acquisition of data and analysis and interpretation of data. EGJ: acquisition of data and analysis and interpretation of data. JB: acquisition of da...
PMC10241827
Funding
This study was sponsored by Incyte Corporation.
PMC10241827
Data availability
Access to individual patient-level data is not available for this study.
PMC10241827
Competing interests
TopAlliance, Cancer
EMD, DEFICIENCY, ONCOLOGY, EDWARDS, CANCER
JJL: DSMB (Abbvie and Immutep); scientific advisory board: ([no stock] 7 Hills, Fstar, Inzen, RefleXion, Xilio [stock] Actym, Alphamab Oncology, Arch Oncology, Kanaph, Mavu, Onc.AI, Pyxis, and Tempest); consultancy fees (Abbvie, Alnylam, Avillion, Bayer, Bristol-Myers Squibb, Checkmate, Codiak, Crown, Day One, Eisai, E...
PMC10241827
Ethics approval and consent to participate
Cancer
CANCER
The study protocol was approved by the independent ethics committee/institutional review board at each institution (BSD/IRB, The University of Chicago Biological Sciences Division/University of Chicago Medical Center; Vanderbilt University Institutional Review Board; Western Institutional Review Board; UC San Diego Hum...
PMC10241827
Consent for publication
Not applicable.
PMC10241827
References
PMC10241827
Purpose
EVENTS, PRIMARY BRAIN TUMORS, LITTLE
Intraventricular compartmental radioimmunotherapy (cRIT) with 131-I-omburtamab is a potential therapy for recurrent primary brain tumors that can seed the thecal space. These patients often previously received external beam radiotherapy (EBRT) to a portion or full craniospinal axis (CSI) as part of upfront therapy. Lit...
PMC10050019
Methods
medulloblastoma, ependymoma
DISEASE, MEDULLOBLASTOMA, EPENDYMOMA
Patients with recurrent medulloblastoma or ependymoma who received 131-I-omburtamab on a prospective clinical trial were included. Extent of disease at cRIT initiation (no evidence of disease [NED] vs measurable disease [MD]) was assessed as associated with progression-free (PFS) and overall survival (OS) by Kaplan–Mei...
PMC10050019
Results
medulloblastoma, ependymoma, radionecrosis
MEDULLOBLASTOMA, EPENDYMOMA
All 27 patients (20 medulloblastoma, 7 ependymoma) had EBRT preceding cRIT: most (22, 81%) included CSI (median dose 2340 cGy, boost to 5400 cGy). Twelve (44%) also received EBRT at relapse as bridging to cRIT. There were no cases of radionecrosis. At cRIT initiation, 11 (55%) medulloblastoma and 3 (43%) ependymoma pat...
PMC10050019