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Adipocyte Dec 2023This systematic review was developed in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-2020) standards. This was... (Meta-Analysis)
Meta-Analysis Review
METHODS
This systematic review was developed in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-2020) standards. This was accomplished by searching clinical MeSH categories in MEDLINE with full texts, EMBASE, Web of Science, PubMed, Cochrane Library, Academic Search Complete, ICTRP and ClinicalTrial.gov. Reviewers examined all the findings and selected the studies that satisfied the inclusion criteria. The Downs and Black Checklist was used to assess for bias, followed by a Review Manager v5. A Forrest plot was used for the meta-analysis and sensitivity analysis. The protocol for this review was registered with PROSPERO CRD42022320252.
RESULTS
The clinical studies ( = 2) comprised 1065 patients with prediabetes and 1103 normal controls. The RAAS measurements were completed in the adipose tissue. The RAAS components, renin and aldosterone were higher in the prediabetic (PD) compared to the control [mean difference (MD) = 0.16, 95% CI 0.16 (-0.13, 0.45), = 0.25]. Furthermore, the PD group demonstrated higher triglycerides mean difference [MD = 7.84, 95% CI 7.84 (-9.84, 25.51), = 0.38] and increased BMI [MD = 0.13, 95% CI 0.13 (-0.74, 0.99), = 0.77] compared to the control. The overall quality of the studies was fair with a median score and range of 17 (16-18).
CONCLUSION
The current study highlights the relationship between increased BMI, RAAS and insulin resistance which is a predictor of prediabetes. The renin is slightly higher in the prediabetes group without any statistical significance, aldosterone is rather negatively associated with prediabetes which may be attributed to the use of anti-hypertensive treatment.
Topics: Humans; Aldosterone; Prediabetic State; Renin; Renin-Angiotensin System; Risk Factors; Adipose Tissue
PubMed: 37606270
DOI: 10.1080/21623945.2023.2249763 -
Journal of Orthopaedic Surgery and... Dec 2023Bone microvascular endothelial cells (BMECs) played an important role in the pathogenesis of glucocorticoid-induced osteonecrosis of femoral head (GCS-ONFH), and...
Exosomes from bone marrow mesenchymal stem cells ameliorate glucocorticoid-induced osteonecrosis of femoral head by transferring microRNA-210 into bone microvascular endothelial cells.
OBJECTIVES
Bone microvascular endothelial cells (BMECs) played an important role in the pathogenesis of glucocorticoid-induced osteonecrosis of femoral head (GCS-ONFH), and exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) may provide an effective treatment. This study aimed to evaluate the effects of BMSC-Exos and internal microRNA-210-3p (miRNA-210) on GCS-ONFH in an in vitro hydrocortisone-induced BMECs injury model and an in vivo rat GCS-ONFH model.
METHODS
BMECs, BMSCs and BMSC-Exos were isolated and validated. BMECs after the treatment of hydrocortisone were cocultured with different concentrations of BMSC-Exos, then proliferation, migration, apoptosis and angiogenesis of BMECs were evaluated by CCK-8, Annexin V-FITC/PI, cell scratch and tube formation assays. BMSCs were transfected with miRNA-210 mimics and miRNA-210 inhibitors, then BMSC-Exos and BMSC-Exos secreted from such cells were collected. The differences between BMSC-Exos, BMSC-Exos and BMSC-Exos in protecting BMECs against GCS treatment were analyzed by methods mentioned above. Intramuscular injections of methylprednisolone were performed on Sprague-Dawley rats to establish an animal model of GCS-ONFH, then tail intravenous injections of BMSC-Exos, BMSC-Exos or BMSC-Exos were conducted after methylprednisolone injection. Histological and immunofluorescence staining and micro-CT were performed to evaluate the effects of BMSC-Exos and internal miRNA-210 on the in vivo GCS-ONFH model.
RESULTS
Different concentrations of BMSC-Exos, especially high concentration of BMSC-Exos, could enhance the proliferation, migration and angiogenesis ability and reduce the apoptosis rates of BMECs treated with GCS. Compared with BMSC-Exos, BMSC-Exos could further enhance the proliferation, migration and angiogenesis ability and reduce the apoptosis rates of BMECs, while BMECs in the GCS + BMSC-Exos group showed reduced proliferation, migration and angiogenesis ability and higher apoptosis rates. In the rat GCS-ONFH model, BMSC-Exos, especially BMSC-Exos, could increase microvascular density and enhance bone remodeling of femoral heads.
CONCLUSIONS
BMSC-Exos containing miRNA-210 could serve as potential therapeutics for protecting BMECs and ameliorating the progression of GCS-ONFH.
Topics: Rats; Animals; Glucocorticoids; Endothelial Cells; Femur Head; Exosomes; Hydrocortisone; Rats, Sprague-Dawley; Osteonecrosis; Mesenchymal Stem Cells; Methylprednisolone; MicroRNAs
PubMed: 38062514
DOI: 10.1186/s13018-023-04440-x -
Determination of cortisone and cortisol in human scalp hair using an improved LC-MS/MS-based method.Clinical Chemistry and Laboratory... Jan 2024Human scalp hair is an easily available but complex matrix for determination of cortisone and cortisol, and has been shown to reflect long-term glucocorticoid exposure....
OBJECTIVES
Human scalp hair is an easily available but complex matrix for determination of cortisone and cortisol, and has been shown to reflect long-term glucocorticoid exposure. Hair glucocorticoid analysis has been used to detect hypo- and hypercortisolism. In this study, we describe the development and validation of a LC-MS/MS method for quantification of cortisone and cortisol in human scalp hair, and provide a novel approach for analysis and interpretation of the results.
METHODS
Improved sample preparation using pulverization and solid phase extraction allowed for low sample volumes (10 mg). Baseline chromatographic separation without matrix interference was achieved by reversed phase chromatography and MRM measurement in negative ion mode. Run-to-run time was 8 min. Mixed model analyses were performed to create individual patterns of cortisone and cortisol concentrations.
RESULTS
Matrix matched calibration curves showed excellent linearity up to 100 pg (analyte)/mg (hair) for both cortisone and cortisol (R>0.995). LLOQ was 1.5 and 1.0 pg/mg for cortisone and cortisol, respectively. Matrix effect was negligible for hair color (recoveries 95-105 %). Cortisone and cortisol concentrations decreased from proximal to distal hair segments, following a predictable, but subject-specific pattern, with less individual variation for cortisone than for cortisol.
CONCLUSIONS
This improved LC-MS/MS method is able to accurately quantify cortisone and cortisol in human hair with minimum matrix interference. This new way of data analysis and interpretation including individual patterns of cortisone and cortisol will be of help with detection of pathological concentrations in both the high - and the low ranges of glucocorticoids.
Topics: Humans; Hydrocortisone; Cortisone; Chromatography, Liquid; Glucocorticoids; Scalp; Tandem Mass Spectrometry; Hair
PubMed: 37485925
DOI: 10.1515/cclm-2023-0341 -
BMC Nephrology Nov 2023Adrenal function tests (Synacthen test) in chronic hemodialysis (HD) patients are currently performed off dialysis. The study aimed to demonstrate equivalence of serum...
BACKGROUND
Adrenal function tests (Synacthen test) in chronic hemodialysis (HD) patients are currently performed off dialysis. The study aimed to demonstrate equivalence of serum cortisol concentrations pre- and during HD, each for standard-dose (250 µg) and low-dose (1 µg) Synacthen test.
METHODS
In a single-center cross-over diagnostic equivalence study, Synacthen tests were performed in four settings, in standard- and low-dose as well as pre- and during HD. Serum cortisol concentration was measured at 30 and 60 min after Synacthen administration, and additionally at 20 min in low dose test. Based on a multivariable linear mixed model the means of cortisol concentration on log-scale were estimated in each dose and test time combination. Differences in means were calculated and the TOST approach was applied to test for equivalence. Equivalence was proven if the 90% confidence interval of the difference of two cortisol means was entirely between - 0.22 and 0.22.
RESULTS
In 28 chronic HD patients, serum cortisol concentrations at 30 and 60 min after Synacthen administration in both standard- and low-dose were shown to be equivalent pre- and during HD. In 10 of 56 low-dose tests, the cortisol peak was already reached after 20 min. However, cortisol concentrations at 20 and 30 min after low-dose Synacthen test pre- and during HD showed no significant difference.
CONCLUSION
These results suggest that the adrenal function test may be carried out during an ongoing HD session, leading to a more patient-friendly performance of the test, less organizational effort and potentially earlier diagnosis of adrenal insufficiency.
Topics: Humans; Hydrocortisone; Renal Dialysis; Adrenal Insufficiency; Cosyntropin; Time Factors
PubMed: 37936106
DOI: 10.1186/s12882-023-03347-3 -
Frontiers in Endocrinology 2023
Topics: Humans; Aldosterone; Hydrocortisone; Neurosecretory Systems; Cardiovascular Diseases
PubMed: 37964959
DOI: 10.3389/fendo.2023.1295655 -
Translational Psychiatry Jan 2024Circulating cell-free mitochondrial DNA (ccf-mtDNA) is a biomarker of cellular injury or cellular stress and is a potential novel biomarker of psychological stress and...
Circulating cell-free mitochondrial DNA (ccf-mtDNA) is a biomarker of cellular injury or cellular stress and is a potential novel biomarker of psychological stress and of various brain, somatic, and psychiatric disorders. No studies have yet analyzed ccf-mtDNA levels in post-traumatic stress disorder (PTSD), despite evidence of mitochondrial dysfunction in this condition. In the current study, we compared plasma ccf-mtDNA levels in combat trauma-exposed male veterans with PTSD (n = 111) with those who did not develop PTSD (n = 121) and also investigated the relationship between ccf mt-DNA levels and glucocorticoid sensitivity. In unadjusted analyses, ccf-mtDNA levels did not differ significantly between the PTSD and non-PTSD groups (t = 1.312, p = 0.191, Cohen's d = 0.172). In a sensitivity analysis excluding participants with diabetes and those using antidepressant medication and controlling for age, the PTSD group had lower ccf-mtDNA levels than did the non-PTSD group (F(1, 179) = 5.971, p = 0.016, partial η = 0.033). Across the entire sample, ccf-mtDNA levels were negatively correlated with post-dexamethasone adrenocorticotropic hormone (ACTH) decline (r = -0.171, p = 0.020) and cortisol decline (r = -0.149, p = 0.034) (viz., greater ACTH and cortisol suppression was associated with lower ccf-mtDNA levels) both with and without controlling for age, antidepressant status and diabetes status. Ccf-mtDNA levels were also significantly positively associated with IC (the concentration of dexamethasone at which 50% of lysozyme activity is inhibited), a measure of lymphocyte glucocorticoid sensitivity, after controlling for age, antidepressant status, and diabetes status (β = 0.142, p = 0.038), suggesting that increased lymphocyte glucocorticoid sensitivity is associated with lower ccf-mtDNA levels. Although no overall group differences were found in unadjusted analyses, excluding subjects with diabetes and those taking antidepressants, which may affect ccf-mtDNA levels, as well as controlling for age, revealed decreased ccf-mtDNA levels in PTSD. In both adjusted and unadjusted analyses, low ccf-mtDNA levels were associated with relatively increased glucocorticoid sensitivity, often reported in PTSD, suggesting a link between mitochondrial and glucocorticoid-related abnormalities in PTSD.
Topics: Humans; Male; Stress Disorders, Post-Traumatic; Glucocorticoids; Hydrocortisone; Veterans; DNA, Mitochondrial; Adrenocorticotropic Hormone; Cell-Free Nucleic Acids; Antidepressive Agents; Biomarkers; Diabetes Mellitus; Dexamethasone
PubMed: 38200001
DOI: 10.1038/s41398-023-02721-x -
JAMA Network Open Mar 2024The association between the use of bone-modifying agents (BMAs) and the outcomes among patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
The association between the use of bone-modifying agents (BMAs) and the outcomes among patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with abiraterone acetate plus prednisone (AAP) remains unclear.
OBJECTIVE
To investigate the association between BMA use and the outcomes of patients with mCSPC receiving AAP.
DESIGN, SETTING, AND PARTICIPANTS
In this cohort study, a post hoc analysis of individual participant data from the LATITUDE trial was performed. The LATITUDE trial, a phase 3 randomized clinical trial, aimed to assess the efficacy of AAP and androgen deprivation therapy (ADT) vs dual-placebo and ADT in patients with high-risk mCSPC (data cutoff, August 15, 2018). Eligible patients had newly diagnosed prostate cancer with metastases and at least 2 of 3 high-risk factors (Gleason score ≥8, presence of ≥3 lesions on bone scan, or presence of measurable visceral metastasis). The trial was conducted at 235 sites in 34 countries. Data for the present study were evaluated from July 18 to September 23, 2023.
EXPOSURES
Use of BMAs was defined as the administration of bisphosphonates and denosumab within 90 days before and after randomization.
MAIN OUTCOMES AND MEASURES
The primary outcomes were time to skeletal-related events (SREs) and overall survival (OS). An SRE was defined as a clinical or pathological fracture, spinal cord compression, palliative radiation to bone, or surgery involving bone. Differences in these outcomes were examined using the restricted mean survival time from inverse probability of treatment weighting-adjusted Kaplan-Meier curves, estimated until the last event was observed (longest time observed, 63.9 months). Treatment × covariate interactions were analyzed using weighted Cox proportional hazards regression models for the total cohort.
RESULTS
In the total cohort of 1199 patients (956 [79.7%] younger than 75 years), 597 (49.8%) received AAP and ADT, including 474 (79.4%) younger than 75 years and 384 (64.3%) with more than 10 bone metastases (AAP cohort); 602 (50.2%) were treated with dual placebo and ADT, including 482 (80.1%) younger than 75 years and 377 (62.6%) with more than 10 bone metastases (ADT cohort). In the AAP cohort, 132 patients (22.1%) received BMAs, while in the ADT cohort, 131 (21.8%) did. Zoledronic acid was the most frequently administered BMA in both the AAP (93 [70.5%]) and the ADT (88 [67.2%]) cohorts. During the median follow-up of 51.8 (IQR, 47.2-57.0) months in the AAP cohort, BMA use was associated with a longer time to SRE (difference, 7.8 [95% CI, 4.2-11.3] months) but not with OS (difference, 1.6 [95% CI, -2.5 to 5.8] months). In the ADT cohort, BMA use was associated with both time to SRE (difference, 9.3 [95% CI, 5.2-13.3] months) and OS (difference, 5.5 [95% CI, 3.2-9.8] months). No evidence was found that the outcomes of BMA varied by AAP or ADT (hazard ratio for time to SRE, 0.99 [95% CI, 0.48-2.08]; P = .99 for interaction; hazard ratio for OS, 1.31 [95% CI, 0.88-1.96]; P = .18 for interaction).
CONCLUSIONS AND RELEVANCE
The findings of this cohort study suggest that use of BMAs was associated with a longer time to SRE in patients with high-risk mCSPC treated with ADT, with or without AAP, suggesting that BMA use might provide benefits to this population.
Topics: Male; Humans; Abiraterone Acetate; Prostatic Neoplasms; Androgen Antagonists; Cohort Studies; Prednisone; Castration
PubMed: 38488793
DOI: 10.1001/jamanetworkopen.2024.2467 -
The Journal of Allergy and Clinical... Sep 2023The Global Initiative for Asthma and National Asthma Education and Prevention Program recently made paradigm-shifting recommendations regarding inhaler management in...
BACKGROUND
The Global Initiative for Asthma and National Asthma Education and Prevention Program recently made paradigm-shifting recommendations regarding inhaler management in asthma. The Global Initiative for Asthma now recommends that combination inhaled corticosteroid (ICS)-formoterol inhalers replace short-acting β-agonists as the preferred reliever therapy at all steps of asthma management. Although the most recent guidelines of the National Asthma Education and Prevention Program did not review reliever ICS-formoterol usage in mild asthma, they similarly recommended single maintenance and reliever therapy (SMART) at steps 3 and 4 of asthma management. Despite these recommendations, many clinicians-particularly in the United States-are not prescribing new inhaler paradigms. Clinician-level reasons for this implementation gap remain largely unexplored.
OBJECTIVE
To gain an in-depth understanding of the facilitators and barriers to prescribing reliever ICS-formoterol inhalers and SMART in the United States.
METHODS
Community and academic primary care providers, pulmonologists, and allergists who reported regularly caring for adults with asthma were interviewed. Interviews were recorded, transcribed, qualitatively coded, and analyzed using the Consolidated Framework for Implementation Research. Interviews were continued until theme saturation.
RESULTS
Among 20 interviewed clinicians, only 6 clinicians described regularly prescribing ICS-formoterol inhalers as a reliever inhaler (either alone or within SMART). Significant barriers to new inhaler approaches included concerns surrounding a lack of Food and Drug Administration labeling for ICS-formoterol as a reliever therapy, a lack of awareness regarding a patient's formulary-preferred ICS-long-acting β-agonist choices, the high cost of combination inhalers, and time constraints. Facilitators to using new inhaler approaches included clinicians' beliefs that the latest inhaler recommendations are simpler and more congruent with real-world patients' behavior, and that a potential change in management strategy would offer a valuable opportunity for shared decision making.
CONCLUSIONS
Although new guidelines exist in asthma, many clinicians described significant barriers to using them including medicolegal issues, pharmaceutical formulary confusion, and high drug costs. Nonetheless, most clinicians believed that the latest inhaler approaches would be more intuitive for their patients and would offer an opportunity for patient-centered collaboration and care. Stakeholders may find these results useful in future attempts to increase the real-world adoption of recent asthma recommendations.
Topics: Adult; Humans; United States; Budesonide; Anti-Asthmatic Agents; Ethanolamines; Administration, Inhalation; Asthma; Budesonide, Formoterol Fumarate Drug Combination; Formoterol Fumarate; Nebulizers and Vaporizers; Adrenal Cortex Hormones; Drug Combinations
PubMed: 37245736
DOI: 10.1016/j.jaip.2023.05.023 -
Scientific Reports Dec 2023Adrenal venous sampling (AVS) is crucial for subtyping primary aldosteronism (PA) to explore the possibility of curing hypertension. Because AVS availability is limited,...
Adrenal venous sampling (AVS) is crucial for subtyping primary aldosteronism (PA) to explore the possibility of curing hypertension. Because AVS availability is limited, efforts have been made to develop strategies to bypass it. However, it has so far proven unsuccessful in applying clinical practice, partly due to heterogeneity and missing values of the cohorts. For this purpose, we retrospectively assessed 210 PA cases from three institutions where segment-selective AVS, which is more accurate and sensitive for detecting PA cases with surgical indications, was available. A machine learning-based classification model featuring a new cross-center domain adaptation capability was developed. The model identified 102 patients with PA who benefited from surgery in the present cohort. A new data imputation technique was used to address cross-center heterogeneity, making a common prediction model applicable across multiple cohorts. Logistic regression demonstrated higher accuracy than Random Forest and Deep Learning [(0.89, 0.86) vs. (0.84, 0.84), (0.82, 0.84) for surgical or medical indications in terms of f-score]. A derived integrated flowchart revealed that 35.2% of PA cases required AVS with 94.1% accuracy. The present model enabled us to reduce the burden of AVS on patients who would benefit the most.
Topics: Humans; Hyperaldosteronism; Retrospective Studies; Adrenal Glands; Venae Cavae; Aldosterone
PubMed: 38081870
DOI: 10.1038/s41598-023-47967-z -
BMC Veterinary Research Sep 2023Aldosterone represents an important target of heart failure therapy and may be a valuable indicator of the renin-angiotensin-aldosterone system activity. However, its...
BACKGROUND
Aldosterone represents an important target of heart failure therapy and may be a valuable indicator of the renin-angiotensin-aldosterone system activity. However, its assessment might be challenging because of the effect of individual factors. In a recent study, intact female dogs showed the highest value of urinary aldosterone-to-creatinine ratio (UAldo:C) compared to other sex categories. In humans and rodents, an influence of progesterone has been reported by several studies. To our knowledge, the relationship between aldosterone and progesterone has not yet been investigated in dogs. The aim of this prospective study was to investigate this relationship in sexually intact Chihuahua females, measuring both hormones twice in the same bitch, that is in anoestrus when progesterone concentrations are baseline and in dioestrus when they are high.
RESULTS
The study population consisted of 14 sexually intact Chihuahua bitches. Serum progesterone (34.06 (21.17-44.90) vs. 0.19 [0.13-0.38] ng/ml; P < 0.001) and urinary aldosterone (9886.98 ± 5735.22 vs. 5005.72 ± 2127.73 pg/ml; P = 0.01) were significantly higher in dioestrus compared to anoestrous. Urinary aldosterone-to-creatinine ratio was higher in dioestrus compared to anoestrus (4.16 [3.17-6.80] vs. 3.39 ± 1.64 µg/g), but it did not reach the statistical significance (P = 0.056). Serum progesterone showed a moderate positive correlation with urinary aldosterone (ρ = 0.638, P < 0.001) and UAldo:C (ρ = 0.516, P = 0.005).
CONCLUSIONS
The results of the present study suggest the existence of a progesterone-aldosterone relationship in canine species, indicating that sex and phase of reproductive cycle should be taken into account when interpreting aldosterone concentrations. Further studies are needed to confirm these results on a larger canine population and to identify the underlying mechanisms in this species.
Topics: Humans; Animals; Dogs; Female; Aldosterone; Progesterone; Creatinine; Prospective Studies; Diuretics; Anti-Arrhythmia Agents; Cardiotonic Agents
PubMed: 37670293
DOI: 10.1186/s12917-023-03704-2